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© Military Pharmacy and Medicine • 2012 • 4Table of ContentsAge-related macular degeneration (AMD): a critical appraisal of diet and dietarysupplements as therapeutic modalities 1Jerzy Z. NowakAssessment of the energy expenditure of soldiers of the Representative Battalion of the Polish Armyduring three days of drill training as part of preparations for the celebration of the NationalIndependence Day of November 11th 17Jerzy Bertrandt, Anna Kłos, Roman ŁakomyAssessment of microbial quality of drinks not included in the hospital diet as consumed bypatients during hospitalization and the assessment of microbial contamination of hospital air 21Jaśmina Żwirska, Wanda Jabłońska, Paweł Jagielski,Stanisław Stępniewski, Małgorzata Schlegel ZawadzkaCholesterol oxyethyleneation products as modifiers of the absorption base inanti-inflammatory ointments 27Justyna Kołodziejska, Marian Mikołaj Zgoda,Katarzyna Ejzenchart, Magdalena Piechota-UrbańskaNon-steroidal anti-inflammatory drugs (NSAIDs) in ophthalmology:pharmacological and clinical characteristics 33Jerzy Z. NowakThe role of paramedics in British emergency aid system 51Dorota Kołodziej, Radosław ZiembaEnergy expenditure as the basis for determination of nutritional demand in soldiers 57Jerzy Bertrandt, Anna Kłos, Bartosz BertrandtSodium and potassium content of daily food rations of students ofthe Main School of Fire Service in Warsaw 61Anna Kłos, Maryla Długaszek, Jerzy Bertrandt, Wiesława SzymańskaCardiac arrest under special circumstances. Part II:poisoning, …, anaphylactic reaction, …, traumatic injuries 67Radosław ZiembaPrevalence of atrial fibrillation in emergency medicine practice 77Łukasz Szarpak, Dariusz TimlerAutopsy marks on anthropological material contributingto research on history of anatomy in Poland 81Magdalena Cybulska, Agnieszka Adamczyk,Agnieszka Młudzik, Czesław Jesmanhttp://military.isl-journals.com/v

© Military Pharmacy and Medicine • 2012 • 4Table of ContentsInfusion solutions supply in critical circumstances and disasters 87Katrzyna Parzuchowska, Radosław Ziemba, Jan Hołyński, Adam Ziemba,Jarosław Hołyński, Ewa ZiembaScope of knowledge regarding administration ofoxygen therapy among firefighterrescue teams from Volunteer Fire Departments (OSP) 91Łukasz SzarpakSustainable development in light of international cooperation 97Radosław ZiembaAnthropological and archeological sources in medical historian’s studies 105Magdalena Cybulska, Agnieszka Adamczyk,Agnieszka Młudzik, Czesław JesmanSelected aspects of communication between emergency servicesand the mass media in crisis situations 113Łukasz Szarpak, Marcin MadziałaBioterrorism — nature of the problem 119Radosław ZiembaAnti-drown ring — a patented drowning protection device (patent no. 197623) 123Jerzy MierzejewskiSpeech made by Commandant of the Military Centre for Pharmacy andMedical Technology in Celestynów, Colonel DMSc Radosław Ziemba 127Radosław ZiembaEditorial policy and general information 133vihttp://military.isl-journals.com/

© Military Pharmacy and Medicine • 2012 • 4 • 1 – 16Jerzy Z. Nowak: Age-related macular degeneration (AMD): a critical appraisal …OphthalmologyAge-related macular degeneration (AMD): a critical appraisal ofdiet and dietary supplements as therapeutic modalitiesJerzy Z. NowakDepartment of Pharmacology, Chair of Pharmacology and Clinical Pharmacology of Medical University ofLodz, PolandAuthor’s address:Jerzy Z. Nowak, Department of Pharmacology, Medical University, ul. Żeligowskiego 7/9, 90-752 Lodz, Poland;phone: ( + 48) 42 6393270, e–mail: jerzy.nowak@umed.lodz.plReceived: 2012.10.12 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Age-related macular degeneration (AMD) is a vision-threatening ocular disease, affecting the central regionof the retina — the macula — and manifesting in the elderly. Its pathogenesis is multifactorial, molecularlycomplex and only poorly recognized. AMD is a degenerative disease, and the degeneration affects primarilythe retinal pigment epithelial (RPE) cells and secondarily the photoreceptors, which leads to disturbances orpartial loss of central vision and legal blindness. Principal processes contributing to the development of thedisease include: oxidative stress, lipofuscinogenesis, drusogenesis and local inflammation (so-called parainflammation).A severe complication of clinically recognized dry form AMD (geographic atrophy) is theaggressive neovascularization originating from choriocapillary system (CNV; wet form AMD). At present,there are no therapeutic agents capable of slowing or inhibiting degeneration process in the photoreceptors-RPE complex, therefore preventive rather than therapeutic modalities are under consideration; they includeproperly adjusted everyday diet and intake of dietary supplements, both rich in antioxidants of which macularpigments (lutein, zeaxanthin, meso-zeaxanthin) are of particular importance. Long-chain unsaturatedomega-3 fatty acids (PUFA-ω3) are also recommended to people with already progressing AMD and at anincreased risk of the disease development. Despite wide commercial offer of “ophthalmic” antioxidative andPUFA-ω3-rich preparations, no convincing evidence is available to date to support their protective activityin AMD patients. AREDS-2 clinical trials that actually approach completion may likely provide moreconclusive answer whether macular pigments (lutein, zeaxanthin) and PUFA-ω3 (EPA, DHA) can really beuseful for AMD patients. The aim of this article is twofold: 1. it presents molecular mechanisms underlyingthe early stages of AMD pathogenesis, which form a platform for the disease development, and 2. it providesa critical appraisal of the prophylactic/therapeutic value of properly profiled diet and the intake of “ophthalmic”dietary supplements rich in macular pigments and omega-3 PUFAs.Key words: Age-related macular degeneration, AMD, oxidative stress, omega-3 fatty acids, macularpigments, prevention, diet, dietary supplements.IntroductionThis article refers to an earlier article by the sameauthor, entitled Dry form AMD — do we knowhow to treat it?, published in 2011 in issue 5(1)http://military.isl-journals.comof Magazyn Lekarza Okulisty [1] — a Polishlanguagejournal specialized in ophthalmologyand widely distributed among ophthalmologists.There are no drugs specific to this condition; the1

© Military Pharmacy and Medicine • 2012 • 4 • 2 – 16therapeutic approach focuses on prophylaxis inthe form of properly profiled diet and the intakeof dietary supplements. The number of these supplementsis constantly growing, and all of themare freely available, i.e. without prescription. Theavailable supplements differ in both qualitativeand quantitative composition. A detailed analysisof supplements available at Polish marketas described by the author in 2010 in an articleentitled Ophthalmic antioxidant preparations:a survey and supportive arguments for their usein AMD [2], included 73 products — all of themcontained the macular pigment — lutein, somecontained also zeaxanthin, and only one containedthree macular pigments, namely lutein,zeaxanthin and meso-zeaxanthin.Currently nearly 100 ophthalmic antioxidantpreparations are available only at Polish market.This does not include numerous preparationscontaining polyunsaturated fatty acidsof the omega-3 series (PUFA-ω3), discussed bythe author in his earlier study entitled Omega-3polyunsaturated fatty acids in retina and medicalpractice — pros and cons [3]. Ophthalmologists,as well as patients, may have and, according toauthor’s knowledge, indeed have problems withchoosing an appropriate preparation. However,resorting to dietary supplement may be perhapsunnecessary if appropriate choice of foodproducts is made for one’s everyday diet. Theauthor hopes that this study, confronting thedietary and supplementation aspects of prophylaxiswill contribute to appreciation of the role ofeveryday diet rich in selected products in AMDprophylaxis and acknowledging the value of suchdiet as not inferior to that of pharmaceuticalsupplementation.AMD – origin and developmentof the pathologyAge-related macular degeneration (AMD) developsinconspicuously over many years. Despitenumerous studies conducted worldwide, thepathogenesis of the disease is not fully understood.Due to the plurality of factors, both endogenous(e.g. genetic predispositions) and exogenous(history of exposure to light) or behavioral(e.g. smoking, improper diet), which might predispose,or even contribute to the developmentof the disease, the critical physiological processesresponsible for the vision process (e.g. the visualReview articleexcitation cascade) move beyond the limits ofhomeostasis, creating a biochemical platform forthe future pathology [4–9]. This involves intensifiedlipofuscinogenesis in retinal pigment epithelium(RPE) cells, formation of drusen andpseudodrusen — the former occurring under theRPE monolayer (i.e. in the direction of Bruch’smembrane), the latter above the RPE monolayer(i.e. towards photoreceptors) and next, a chronicinflammatory process known as para-inflammation.All these phenomena contribute to thedevelopment of AMD. Clinically, AMD can bedivided into the dry, or atrophic, form (knownas geographic atrophy), and wet — exudative, orneovascular form; the latter can be considered acomplication of the atrophic form manifesting aschoroidal neovascularization (CNV) [1,4,5].Aging favors the development of AMD, particularlyin predisposed individuals (due to concomitantpresence of the risk factors listed above); theterm “age-related” in the disease name – AMD isfully justified, as the age is the major (albeit individual,i.e. specific to each subject) and unavoidabledeterminant of various dysfunctions at thecellular and organ level, including these associatedwith the deficiency of necessary microelements/nutrientsor with the loss of function inthe aging cells — particularly post-mitotic, i.e.non-regenerable cells. While the lacking microelements/nutrientsmay be supplied from theoutside, thus attempting to compensate for theirdeficiency in particular cells/tissues, we are unableuntil now to stop the systemic aging process.Our bodies contain many non-regenerable (postmitotic)cells, particularly within the centralnervous system. These include the photoreceptors(only the external segments that containphotopigments are subject to regeneration) andretinal pigment epithelium (RPE) cells. In thepathogenesis of AMD, RPE cells are the first cellsthat become metabolically inefficient and thusundergo degeneration; dysfunction and atrophyof photoreceptors is secondary, as they are unableto function and survive without functionallyefficient RPE cells, and therefore also undergodegeneration. The pathological process involvesmostly a small region of the retina, known asthe macula, where cone photoreceptors, responsiblefor acute and color vision, are predominant.Therefore, first clinical symptoms of AMDinclude blurred vision, defects of central vision of2 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 3 – 16Jerzy Z. Nowak: Age-related macular degeneration (AMD): a critical appraisal …various intensity or gradual loss of color vision,“warping” of perceived images [10,11]. Early formof AMD is often referred to as age-related maculopathy(ARM).When the eyes are open, photoreceptors arecontinuously working, absorbing light photonsand “recording” the image of the environment.Similarly to TV cameras being turned on, eyesrecord this image in an automatic fashion, generatingthe first signal of a complex, multisynapticvision process. Photoreceptors’ outer segments(POS), filled with visual pigment molecules, arecharacterized by significant functional dynamics;they wear off upon continuous function and,as a consequence, the apical fragments are constantlyshed and captured by neighboring RPEcells. At the same time, POS is being rebuilt inorder to maintain appropriate size (which is animportant parameter determining the efficacyand survival of photoreceptors!). Regenerationproceeds from the perikaryon, i.e. the photoreceptorinner segment (PIS) and requires numerousbuilding blocks, including docosahexaenoicacid (DHA). These building blocks are suppliedby the RPE cells and originate partly from thecaptured POS fragments and partly from circulation(consumed food) [9].One of the many important roles played by theRPE cells is “digestion” of the absorbed (and continuouslybeing absorbed) photoreceptor materialstored in phagolysosomes. Despite the factthat phagocytosis and enzymatic degradationoccurring as a result of the activity of numerouslysosomal enzymes are physiological processesthat had developed over thousands of years increatures dwelling on Earth and making use ofthe visual organ system (retinal processes thatgovern visual perception in many vertebrates,including humans, are generally very similar),they seem to be of limited efficacy, at least inhumans. This claim is supported by systematicaccumulation of lipofuscin, known as the agepigment, in RPE cells.Lipofuscin and the process of its formation, i.e.lipofuscinogenesis, are not the attributes of RPEcells and connections between photoreceptorsand RPE, as they are also present in other nonrenewablecells, such as neurons, cardiomyocytesor skeletal muscle cells. However, it is in thisregion of the eye, or more precisely, of the retina,http://military.isl-journals.comi.e. in the photoreceptors/RPE cells region, wherea unique characteristics of lipofuscin accumulatedin RPE cells becomes evident: lipofuscincontains retinoids (vitamin A derivatives) originatingfrom the visual cycle, particularly bisretinoids— products of spontaneous fusion oftwo molecules of all-trans-retinal, generated viaphotoreaction (i.e. by absorption of photons) by11-cis-retinal, a cofactor of the visual pigment.The cis → trans retinal transformation is the crucialfirst step of visual cycle, initiating furtherconformational transformations of opsin (i.e.the visual pigment protein) into its active forms(e.g. meta-rhodopsin II), capable of progressingthe visual cycle with the final effect consistingin the closure of cGMP-dependent cation channelin the cellular membrane of photoreceptorsand quenching the so-called darkness current.In this time, the cellular membrane of photoreceptorsis hyperpolarized only to regain the stateof being ready to absorb another photon, i.e. thedepolarization state; the active pigment, capableof absorbing photons, is a molecule, e.g. rhodopsin,that contains a light sensitive co-factor,11-cis-retinal [5,6].The all-trans-retinal formed following photonabsorption is completely dissociated from the visualpigment and undergoes further physiologicaltransformations in the retinoid cycle that takesplace in both photoreceptors and RPE cells. However,part of all-trans-retinal that does not bindthe ABCA4 (ATP-binding cassette [transporter]A4 type, also known as ABCR) transportingthe retinoid into the sites with all-trans-retinaldehydroghenase activity, “falls out” the cycle andspontaneously dimerizes (using ethanolamineas a “linker”) into a highly phototoxic bisretinoidknown as A2E. There may be more similarand toxic bisretinoids; however, A2E, which hasbeen studied in more detail, seems to representan established stress-inducing product. Furano– and peroxy –mtabolites of A2E have significantability to activate the complement system(an alternative pathway) which represents theinnate immunity, capable of efficiently and automaticallyacting in system’s defense, includingdestruction of “own” cells [5,12].In addition, the photoreceptor cell membranescontain exceptionally high amounts of polyunsaturatedfatty acids (PUFAs), particularly the3

© Military Pharmacy and Medicine • 2012 • 4 • 4 – 16most-unsaturated docosahexaenoic acid (DHA).It is this high unsaturation (six double C=Cbonds in the hydrocarbon chain) makes DHAparticularly susceptible to spontaneous peroxidationand fragmentation into cytotoxic compounds,including 4-hydroxy-2-hexenal (HHE)or 4-hydroxy-7-oxyhept-5-enoic acid (HOHA);the latter may additionally form immunogeniccarboxyethylpyrrole-protein (e.g. CEP-albumin)adducts. More details regarding formationof the products of peroxidation of long-chainPUFAs and the properties of carboxyethylpyrrole-proteinadducts are available in other articlesby the same author [2,5].Accumulation of lipofuscin deposits in RPEcells is a manifestation of metabolic inefficacyof their lysosomal compartment, characterizedby reduced autophagy. The reason for thisinefficacy remains unknown, although consideringmolecular complexity of autophagic processes,the reasons may be multiple, includinghypofunction or insufficient quantity/activityof lysosomal enzymes – cathepsins being mostpredominant in normal conditions. Lipofuscindeposits accumulate with age, and the adverseeffect of accumulating oxidative stress thataccompanies lipofuscinogenesis is intensified.Local inflammatory reaction that develops atcertain moment and is manifested by an atypicalprocess referred to as para-inflammation, aswell as drusogenesis (drusens, pseudodrusens),become the driving forces of the developingAMD pathology [4-7, 13].One should not forget that the supply of oxygen(and microelements/nutrients) via the choriocapillarysystem into the photoreceptors-RPE cellscomplex is one of the largest in primates. Takinginto account the functional specificity of theretina, particularly of photoreceptors (photosensitivity,extensive metabolism, high partial pressureof oxygen being the substrate for the formationof oxygen radicals), one may suspect thatretina is particularly well predisposed for formationof reactive oxygen species (ROS) [14].The nature must have predicted the potentiallyadverse, propathogenic processes, such as oxidativestress or lipofuscinogenesis, in the retina, asthe tissue, and particularly the macular region,very important for acute and color vision inprimates, has been equipped with an array ofReview articleantioxidative defense systems, including specificmacular pigments (MPs) – lutein and zeaxanthinand meso-zeaxanthin produced from lutein [15].It should also be mentioned that the classical antioxidativesystems present within the body are classifiedas either enzymatic or non-enzymatic. Enzymaticsystems include three basic enzymes: superoxide dysmutase(SOD), catalase and glutathione peroxidase,which are dependent on metal ions, such as zinc,copper, manganium or selenium. The non-enzymaticsystem consists of carotenoids (including theaforementioned macular pigments), vitamins E andC and glutathione. The enzymatic system is endogenous;however, the metal ions that are required forits proper function are exogenous, i.e. must be suppliedwith food. As far as the non-enzymatic systemis concerned, only glutathione is an endogenous antioxidant.The remaining elements of the system, i.e.carotenoids and vitamins E and C are exogenous factorssupplied with food or appropriate dietary supplements.The role of carotenoids is to neutralize singletoxygen and reactive free radicals. What’s interesting,the mechanisms underlying these two activities ofcarotenoids are different and neutralization of freeradicals may, in certain conditions (e.g. those whenexcessive amounts of radicals are present), changethe antioxidative activity of these compounds intoprooxidative activity.Proper functioning of retinal antioxidationdefense systems is believed to avert potentialearly propathogenic changes that may lead toAMD. These propathogenic changes are in factphysiological reactions that become functionally(chemically) impaired due to their intensityand the accompanying overproduction of reactiveoxygen species (ROS), crucial transformationsof “visual” retinoids and peroxidation andfragmentation of long-chain PUFAs. This may begenerally due to indisposition of the aging body– its organs, tissues and cells, and hypofunctionof the aforementioned antioxidative defense systems,both enzymatic and non-enzymatic. Sincethese systems are dependent on the supply ofexogenous nutrients, thus their activity is dietdependent[2,14–17].A diversified diet, containing vegetables rich incarotenoids, or — more precisely — oxycarotenoidsor xanthophylls (mainly lutein and zeaxanthin;meso-zeaxanthin is not of dietary origin, beingproduced locally from lutein) — should be the4 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 5 – 16Jerzy Z. Nowak: Age-related macular degeneration (AMD): a critical appraisal …first recommendation for patients in whome AMDdevelopment is suspected on the basis of generallydiscrete symptoms, albeit disturbing visualsensations.DietSpecific dietary recommendations are crucialin many ailments and diseases. For instance,in diabetic patients, diet is an integral elementof therapy, as no therapeutic success can beachieved in these patients without an appropriatelyprofiled diet. Gluten-free diet is necessaryin individuals, particularly children, with glutenintolerance. Patients with arterial hypertensionshould avoid salt, i.e. sodium chloride, in theirdiet. Excess sodium ions retain water in the bodyvia a kidney-based mechanism; thus the dailydietary content of sodium should be well below85 mmoles (less than 5 g NaCl) — in practice, oneshould follow the rule “the less salt, the better”.Many examples may be provided, but how abouta diet for AMD patients?Indeed, appropriate dietary recommendationsfor AMD patients are well justified, although oneshould expect no miraculous effects of such diets.Individuals who rigorously follow dietary recommendations(abundance of selected vegetablesrich in lutein, marine fish rich in PUFA-ω3, etc.)also suffer from AMD. This is the nature of thedisease, as it develops inconspicuously over manyyears and becomes symptomatic after the age of50, most frequently after the age of 60. Its backgroundis multifactorial, including both environmental/geneticand inflammatory/immune factors;in general opinion, there is no way to avoidit, as reported by the author in numerous studies[1, 2, 4, 5, 18]. Nonetheless, appropriate diet isimportant in AMD patients.Considering the threat of AMD or active AMD,one should recommend vegetables that containhigh amounts of macular pigments (MPs),i.e. lutein and zeaxanthin [19]. Recommendedvegetables include spinach, corn, pumpkin, redgrapes (particularly seedless grapes), broccolietc. (a more detailed list is presented in Table 1),as well as egg yolk which contains high amountof zeaxanthin in addition to lutein [15, 20]. It wascalculated that the average Western diet contentof lutein and zeaxanthin is between 1.3 and 3 mg,with lutein to zeaxanthin ratio of 7:1 [21, 22]. Ahttp://military.isl-journals.comproperly profiled diet may contain more macularpigments, and therefore be more beneficial forindividuals with AMD. Macular pigments areguards of metabolic order in the macular regionand play a dual role of a filter, as they absorb bluelight which is most dangerous for eyes and of ascavenger of free radicals, as they neutralize singletoxygen and continuously generated free oxygenradicals.Table 1: The content of lutein and zeaxanthin in widelyused vegetables and fruits, given in mol %.ProductsLutein andzeaxanthinLutein ZeaxanthinEgg yolk 89 54 35Corn 86 60 25Kiwi fruit 54 54 0Red seedlessgrapes53 43 10Pumpkin 49 49 0Spinach 47 47 0Cucumber 42 38 4Celery 34 3 2White grapes 31 25 7Brusselssprouts29 27 2Green peas 25 22 3Broccoli 22 22 0Mango 18 2 16Lettuce 15 15 0Properly selected daily rations of selected vegetablesprovide the body not only with macularpigments, but also with microelements (includingzinc, copper, manganese, selenium, vitaminsE and C) required for proper functioning of antioxidativeenzymes (superoxide dysmutase, catalase,glutathione peroxidase).One should not forget other important dietary elements,i.e. unsaturated fatty acids of the omega-3series, particularly DHA [1] , abundantly present inmarine fish [2] . Two or three fish-based meals per[1] DHA is an example of a compound of dual nature, both beneficial and adverse. On onehand, DHA is required for the function of many cells, tissues and organs; on the other hand,due to its unsaturation, it is associated with the risk of adverse phenomena; at the sametime, its functional indispensability is associated with structural unsaturation. The prosand cons of DHA were discussed in more detail in [3]. A disadvantage of DHA, as well as ofother long-chain polyunsaturated fats, including the omega-3 eicosapentaenoic acid (EPA),omega-6 arachidonic acid (ARA or AA), or docosapentaenoic acid (DPA) is that in the presenceof oxygen they easily undergo peroxidation and cleavage leading to propagation of oxidativestress. Despite the dual nature of the omega-3 fatty acids (DHA, EPA, DPA), one should notavoid their presence in food, particularly in the context of AMD prevention. The presenceof vitamin E in food/supplement protects long chain polyunsaturated fats from oxidation.[2] Marine fish contain high amounts of long-chain polyunsaturated fatty acids (PUFAs),including acids of the omega-3 series (PUFA-ω3). Of tested and commonly eaten fish5

© Military Pharmacy and Medicine • 2012 • 4 • 6 – 16week (e.g. salmon, herring, mackerel) provide thebody with these fatty acids in amounts sufficientnot only for needs of the organs of vision, but alsoof the entire system.Polyunsaturated fatty acids of the omega-6 series(PUFA-ω6), also essential for human body, areusually consumed in high amounts, as they arepresent in commonly used vegetable oils – e.g.linoleic acid (C18:2ω6 or C18:2n-6, which is thefirst acid in the omega-6 series) is abundant ingrape seed oil and sunflower oil (63–66%), aswell as in corn oil and soybean oil (55–56%);other oils have much lower contents of linoleicacid (rape oil, linen oil, olive oil — 10–21%). Incase of PUFA-ω3, the case is more difficult, asEPA and DHA are virtually absent in vegetableoils, while alpha-linolenic acid (ALA; C18:3ω3or C18:3n-3, being the first acid in the omega-3series) is present only in moderate amounts inrape oil and soybean oil (7–11%), as well as inlarge amounts (!) in linen oil (55%) [3] . For thesake of comparison, the overall PUFA-ω3 (ALA,EPA and DHA) content in fish oil (herring oil)is > 28%, while the linoleic acid (ω6) contentis slightly above 12%. Cold-pressed linen oil isavailable in an increasingly broad commercialoffer. Although not everyone finds it tasty, linenoil is a recommended addition to the diet, notonly of AMD patients. However, one shouldremember that conversion of ALA into EPA orDHA in human body is very low, and thereforethe supply of ALA may not substitute for directsupply of DHA and DPA (which are abundantin marine fish).species, highest amounts of DHA and EPA (expressed overall in g/100 g of weight) canbe found in Atlantic salmon (> 2; farm-raised and wild caught) and herring (mainlyAtlantic herring ≈ 2), then in mackerel and tuna (1.2–1.5); the popular canned tunacontains much smaller amounts (0,3–0,8); less DHA + EPA can be found in halibut andcod (0,2–0,6), while a higher content can be found in trout (farm-raised and wild caught)(≈ 1). As far as DHA is concerned, the highest content can be found in salmon, herringand tuna (excluding canned tuna in brine) and trout. Although fish contain particularlyhigh amounts of EPA, DHA and DPA, other natural sources of these acids are human milk,farm-grown marine algae, marine mammals and krill; as mentioned in the article, somevegetable oils, including linen oil, do not contain EPA and DHA, although they may containlarge amounts of alpha-linolenic acid (PUFA-ω3).[3] The percentage composition of selected fatty acids in the linen oil is as follows:alpha-linonenic acid (18:3ω3) – 54.5%, oleic acid (18:1ω9) – 19.7%, linoleic acid (18:2ω6)– 16.2%, palmitic acid (16:0) – 5.1%, stearic acid (18:0) – 3.7%, other acids – 0,8%. Thelinen oil contains no EPA or DHA. The ω6/ω3 ratio is 0.3. For the sake of comparison, thepercentage composition of fish oil (herring oil) is as follows: eicosapentaenoic acid (EPA;20:5ω3) – 17.2%, palmitic acid (16:0) – 13.9%, palmitoleic acid (16:1ω7) – 13.1%,linoleic acid (18:2ω6) – 12.4%, oleic acid (cis-Δ 9 -octadecenoic acid; 18:1ω9) – 11.6%,docosahexaenoic acid (DHA; 22:6ω3) – 9%, myristic acid (tetradecanoic acid; 14:0) – 7.4%,stearic acid (octadecanoic acid; 18:0) – 2.7%, linolenic acid (18:3ω3) – 2.1%, elaidicacid (trans-Δ 9 -octadecenoic acid; 18:1ω9) – 2%, gadoleic acid (cis-Δ 11 -icosenoic acid;20:1ω9) – 1.5%; ω6/ω3 ratio = 0.4.Review articleModern diet, particularly the Western diet, isrich in the fatty acids of the omega-6 series, andthe ratio of these acids to the omega-3 (ω3) acidsmay be as high as 20:1, or even higher! The properratio should be about 4:1, with a trend towardsbalanced supply of both types of acids; this leadsto the natural need for omega-3 acids supplementation(EPA, DHA, ALA and docosapentaenoicacid — DPA-ω3); in case of AMD, DHA is of thehighest importance. Despite its disadvantages(easy peroxidation and fragmentation), DHAis absolutely necessary for regeneration of photoreceptorouter segments worn off in the processof vision as well as to maintain appropriateplasticity/susceptibility of the cell membrane inrods and cones. In addition, EPA and DHA aresubstrates for production of anti-inflammatoryresolvins and maresins (the latter are formedonly from DHA) which are very important forthe photoreceptors-RPE cells complex. DHA isalso a substrate for production of neuroprotectin,which is involved in many protective, antiinflammatoryand cytoprotective mechanisms[8]. More information on the pros and cons ofDHA may be found in a recent article by thesame author [3].The advantage of thus-profiled diet (as mentionedabove) is that the elements valuable, among others,for intraocular metabolism, are deliveredto the organism in natural, purely physiologicalfashion, which guarantees optimum gastrointestinalabsorption and transport to target tissues/cells as long as a diversified and well-balanceddiet is maintained. One should remember thatthese microelements, being so important notonly for AMD patients, are absorbed into circulationfrom the gastrointestinal tract in a diversemanner, as they represent different types ofchemical structures and molecular mass ranges.Well-balanced diet containing diverse proteins,carbohydrates and all types of fats (long – andshort-chain, saturated and unsaturated) establisheswithin the stomach and the intestines anatural chemical environment that favors passiveor active absorption of microelements suppliedwith food.This natural, physiological situation is very muchdifferent from situation taking place in the stomach(oftentimes an empty one) after ingestion ofdietary supplement tablets/capsules followed bya glass of water! Microelements contained in the6 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 7 – 16supplements, albeit selected, have no optimumconditions for absorption. This accounts for thesuperiority of comprehensive natural nutritionover the intake of selected substances containedin dietary supplements, which do not have tobe (and, in fact are not) fully absorbed from thegastrointestinal tract. A separate issue relates tothe substances being delivered just where theyare needed, which is a problem not less importantfrom the standpoint of efficacy and expectedresults, and providently passed over in silence bythe producers or suppliers of dietary supplements.However, some individuals may, for various reasons,including the fact that preparation of appropriatemeal requires time and effort, while swallowinga capsule “solves the problem”, may preferready-made dietary supplements. Therefore, thedietary supplements must also be included in ourconsiderations.Dietary supplements and the efficacyof AMD prophylaxis/treatmentFrom the medical standpoint, the issue as statedin the heading is of primary importance for awide group of mature population at risk of discomfortsassociated with the developing orpotential AMD. As mentioned before, pathogenesisof the disease is still unknown, which makesit impossible to both early diagnose the developingpathology and to efficiently treat it usingappropriate medications.Jerzy Z. Nowak: Age-related macular degeneration (AMD): a critical appraisal …first registered drug for the treatment of neovascularAMD [23].However, when starting the treatment of CNV, oneshould keep in mind, that:1) the use of anti-VEGF medications will be efficaciousonly in VEGF-dependent neovascularization (luckily,in a large group of patients CNV is started froma VEGF-dependent process; however, a blockade,particularly a prolonged blockade of this angiogenicpathway may lead to spontaneous switch to anotherangiogenic pathway, which may depend on PDGF,FGF, CEP, or other factors; also possible is that a non-VEGF-dependent mechanism of neovascularization isactivated first – in this case, the CNV process will berefractory to anti-VEGF medications); and2) fighting neovascularization is a symptomatictreatment , as the AMD pathology continues todevelop despite pharmacological inhibition ofneovascularization and/or elimination of alreadyformed pathological vessels using verteporfin-basedphotodynamic therapy (PDT).How should one therefore manage AMD, particularlythe dry (atrophic) form of AMD? Thereare no appropriate drugs or reliable diagnosticmethods for early stages of the disease. Whatremains is only physician’s intuition and knowledge,and prophylactic rather than therapeuticactions. Since the diet has been discussed above,let’s focus on dietary supplements.This does not pertain to the neovascular form of AMD,originating from choroidal neovascularization andconsidered by many researchers, including the authorof this article, to be a serious complication of advancedAMD. This form, or more precisely, the dynamic neovascularizationthat accompanies AMD, may currentlybe treated pharmacologically using agents thatneutralize the main proangiogenic factor, i.e. thevascular endothelial growth factor (VEGF). Followingagents are available: monoclonal anti-VEGF-Aantibodies (Avastin – bevacizumab, Lucentis – ranibizumab),the recently registered soluble decoy receptorfor the factors of the VEGF-A family, VEGF-B andplacenta growth factor – PlGF (Eylea – aflibercept),as well as the less commonly at present used modifiedpegylated aptamer, an oligonucleotide strongly andselectively binding the VEGF-A 165protein, thus inhibitingits activity (Macugen – pegaptanib sodium) – thehttp://military.isl-journals.comThe dietary supplements or, more precisely, “ophthalmic”supplements, as their trade names oftenrefer, either explicitly or implicitly, to the eye orthe retina, include ophthalmic antioxidant preparations(OAPs) and preparations containingPUFA-ω3. Recently, a trend is observed to combinethe active ingredients so that one capsule/tablet containsboth macular pigments (lutein ± zeaxanthin),microelements, and PUFA-ω3. Thus, the capsulesbecome ever bigger in size, making them hard toswallow without plenty of water.This, however, is not as important as the qualitativeand quantitative composition of the offeredproducts/ingredients. This may be completelyarbitrary, including specific substances (suchas lutein and zeaxanthin, vitamins, metal salts)and less precisely defined ingredients such asplant extracts with presumed antioxidative7

© Military Pharmacy and Medicine • 2012 • 4 • 8 – 16or cytoprotective properties or, as in the caseof PUFA-ω3 – extracts from the livers of e.g.shark, cod or other fish, without any quantitativespecification with regard to DHA, EPA andother fatty acids possibly included in the extract.Many producers seem to adhere to the motto:“the more, the better”, and therefore the dosageof the active ingredients is higher than in competingproducts: some products contain as muchas 20 or more milligrams of lutein per capsule or,besides plant extracts, contain substances whichhave no chance of arriving at ocular tissues inuntransformed, active form (e.g. the tripeptideglutathion) — the goal of all these endeavors isto differentiate the product from other productsavailable at the market and thus promote thepurchase.However, the question whether the therapeuticefficacy of dietary supplements, including OAPs,is an established fact or wishful thinking remainsunanswered. What complicates the problem arevaried clinical data being published: accordingto some studies, macular pigments (lutein, zeaxanthin)may have effects protecting against thedeveloping AMD [24–28], while other authorssuggest that no such effects can be observed [29–33]. The former suggest that the use of OAPs inAMD (both in prevention and treatment) is justified,while the latter would preclude such conclusionor suggest to think over the decision beforepharmaceutical supplementation.As mentioned earlier, macular pigments arechemical substances present in large quantitiesin the retina, particularly in the macularregion. Exogenous supply of these compounds(e.g. as part of the diet or as dietary supplements)is assumed to lead to the increase in their retinallevels/concentrations. Indeed, the intake oflutein-containing dietary supplements leads toan increase in both the serum lutein level and themacular pigment optical density (MPOD) – bothparameters are increased in parallel [34]. The lattervalue, i.e. the increased MPOD, is ascribed tobe associated with the positive effect of supplementationon the improvement of vision; however,there are still no clinical data that wouldjustify this opinion!Many researchers measure the MPOD – sometimesin addition to clinical evaluation of vision inpatients developing AMD, and sometimes as the onlyReview articlemeasurement ever made. One should keep in mindthat reliable MPOD readout is subject to certain limitationsstemming from the measurement method, asendogenous lipofuscin also emits light, which mightinterfere with the measurement. For instance, lipofuscinmay be excited by light in the wavelength range of400-580 nm to emit fluorescent light in the spectralrange of 500-800 nm; on the other hand, the macularpigments absorb blue light at wavelengths shorter than550 nm, with the absorbance peak at 460 nm [35]. Inorder for the obtained MPOD readout to be reliable,i.e. free of interferences from (auto)fluorescence oflipofuscin, a special methodological approach shouldbe made, such as the use of dual wavelengths to excitethe macular pigments, e.g. 488 nm (well absorbed byMPs) and 514 (minimally absorbed by the MPs) [33],and conclusions should be drawn from the differencesin measured values. Another factor very importantfor interpretation of the MPOD results, particularlyin AMD patients, is that macular pigments are usuallycharacterized by very slow turnover rates. Thismeans, that in patients taking dietary supplementsincreased levels of macular pigments in serum andmacula (MPOD) would persist for long periods afterthe dietary supplements, e.g. lutein-rich supplements,are discontinued. Sometimes, such periods may lastseveral months or longer.In the context of increasing popularity of PUFA-ω3dietary supplements being recommended to AMDpatients, Delyfer et al. [37] studied the potential relationshipbetween MPOD and serum PUFA-ω3 levelsin 107 healthy volunteers (PIMAVOSA study). Theauthors confirmed the correlation between MPODand serum lutein/zeaxanthin, and additionally identifiedhigh correlation between MPOD and serumPUFA-ω3 (overall levels). When considering the main3 acids of the omega-3 series separately, observationsregarding correlations between the acid levels andMPOD were as follows: DPA — high correlation, EPA– intermediate correlation, DHA – no statistically significantcorrelation. Thus, the French authors pointedout another factor that might affect the MPOD value,i.e. the PUFA-ω3, levels/concentrations of which (e.g.in serum) increase after the intake of meals or dietarysupplements rich in these acids.Among recently published data on macularpigments supplementation and its influence onquality of vision in AMD patients, the authorwould like to take as an example one article,which appeared in PubMed database on August1, 2012, and was published only in November8 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 9 – 16issue of Ophthalmology [38] — it presents dataon the effect of supplementation with lutein (10and 20 mg per day) and zeaxanthin (10 mg perday) for 48 weeks on MPOD and best correctedvisual acuity (BCVA) in 108 patients with earlyAMD. The results are similar to those publishedearlier by other authors, and therefore itis worth to present the conclusions drawn fromthese results (as the conclusions may as wellpertain to the earlier works): „Among patientswith early AMD, supplementation with luteinand zeaxanthin improved macular pigment,which played a causative role in boosting visualfunction and might prevent [highlighted by theauthor] the progression of AMD. Future studiesare required to evaluate the effect of these carotenoidson the incidence of late AMD”. In otherwords, lutein and zeaxanthin, as expected,increased the value of MPOD (i.e. increased thepigment levels), while their effect on vision wascomparatively small, and the preventive effectwith regard to AMD was debatable.Recent Cochrane review, based on randomized,controlled studies in more than 62,500 subjectsalso reports the lack of effects of some widelyrecommended antioxidant supplements [39].The author’s conclusions are as follows: “Thereis accumulating evidence that taking vitamin Eor beta-carotene supplements will not prevent ordelay the onset of AMD. There is no evidence withrespect to other antioxidant supplements, such asvitamin C, lutein and zeaxanthin, or any of thecommonly marketed multivitamin combinations.Although generally regarded as safe, vitaminsupplements may have harmful effects and clearevidence of benefit is needed before they can berecommended.”Ophthalmologists are divided in their practicalobservations in AMD patients receiving OAPs.Many of them ask the well-justified question:Can OAPs cure AMD, delay its progression, orbetter yet, prevent its development? Consideringthe marketing activity of OAP manufacturers, aswell as the ever-increasing number of commerciallyavailable “antioxidant” preparations withvaried qualitative and quantitative compositions,one may have serious doubts regarding the actualtherapeutic value of OAPs. The most importantfactors affecting the “aye” or “nay” decisionfor ophthalmic antioxidant preparations andPUFA-ω3 preparations are presented below.http://military.isl-journals.comJerzy Z. Nowak: Age-related macular degeneration (AMD): a critical appraisal …Dietary supplements vs. drugsContrary to drugs, i.e. registered medicationswith precise and constant composition of activesubstance(s) and excipient(s) and documentedtherapeutic potential, dietary supplements mayhave variable compositions and informationleaflets, if included, are often laconic or lackingdetail. Self-respectful manufacturers presentcomposition, and even intended use/indicationsfor their products, sometimes referring to publishedresults of research suggesting potentiallybeneficial effects of the components of thesecomponents. And this is pretty much all. Conclusion:There is no equals sign between a dietary supplementand drug, although many manufacturerswould like their products being treated as drugs.Dietary supplements are sold freely, and thereforeeveryone may purchase them and use them,either recommended by the doctor or at one’sown discretion, oftentimes prompted by loud,albeit imprecise and sometimes groundlessinformation/messages regarding the efficacy ofthese supplements presented by the mass media.Dietary supplements must not contain ingredientswhich, when used in excess (i.e. in a reasonableexcess, as nearly everything consumed inappropriate excess might have detrimental effectson health) might have any adverse effects. Dietarysupplements should therefore be absolutelysafe, as manufacturers want to avoid medicalproblems resulting from the intake of their productand potentially leading to elimination of suchproduct from the market.Many physicians, while recommending dietarysupplements, including OAPs, to their patients,do not fully believe in therapeutic effects thereof.Some even say that such preparations do no harmwhile they might actually help (!) etc., so thatpatients may take them safely hoping they wouldreally help. However, the despaired patientsexpect the purchased product(s) to have beneficialeffects — they trust their physicians andbelieve, or try to believe, that the product willbe efficacious. Patients perceive the paeans presentedby the mass media to be reliable information,not marketing tricks, which, unfortunately,is not always true.Let’s assume that a patient purchased a packagingwith a month’s supply of the dietary supplement9

© Military Pharmacy and Medicine • 2012 • 4 • 10 – 16recommended to him/her by his/her physicianand that he/she started the treatment. How longshould the patient take the recommended product?And, what’s more important, when shouldthe patient expect to experience an improvementin vision? There are no satisfactory answers tothese well justified (as the patient does not get theproducts for free — he/she buys them) questions,as the beneficial effect will surely not be observedafter the first month, or even after the first severalmonths of using the dietary supplement(s); insome patients, the effect may be observed after along-term use that lasts many months, and evenyears. What’s more, there may be no effect at all!Patients may feel disappointed with such “supplementationtherapy”, while the manufacturer ofthe supplement holds no responsibility whatsoever,as they may always bring up what is alreadywell known, i.e. that the product is a dietary supplement,and not a drug! A question/statementoften raised in such cases by the supporters of“supplementation therapy”, i.e. what if the supplementshad not been taken, is purely rhetoricalone. Indeed, there is no answer to this question.Patients disappointed with their hitherto ineffectivetherapy, i.e. patients with conditions refractoryto the established pharmaceuticals or patients withconditions with no pharmacological treatmentavailable are particularly susceptible to the use ofdietary supplements. Cases where no specific drugsare available — as in the case of AMD — favorsall kinds of therapeutic speculations and paramedicalactivities, opening a lucrative area for themanufacturers and suppliers of dietary supplements— appropriately promoted dietary supplementsmay even be perceived as drugs!The abundant offer of dietary supplements availableat Polish market and targeted at individualssuffering from AMD or at risk of AMD includesnearly 100 products of the OPA type. In a recentstudy, published in 2010 [2], the author analyzed73 ophthalmic antioxidant preparations, i.e. allproducts commercially available in Poland at thattime. The call sign of all OAPs is the presence ofthe macular pigment–lutein; some products containalso another macular pigment, i.e. zeaxanthin(e.g., in alphabetical order, Klarin Perfekt,MaxiVision Total, Nutrof Total, Ocuvite LuteinForte, Vislea), and one product (Macushield)contains three pigments–lutein, zeaxanthin andReview articlemeso-zeaxanthin in one capsule. The analysis ledto the following conclusions:••All 73 preparations contained lutein in theamounts of 0.125/6–10/50 mg (the range of6–10 mg was most common), with 7 preparationsnot stating the precise dose;••30 preparations contained also zeaxanthinin the amounts of 0.12–2.4 mg, with nodata regarding the dose provided for 3preparations;••1 preparation contained meso-zeaxanthin inaddition to the two above pigments;••52 products contained vitamin E;••42 products contained zinc and/or selenium;••9 products contained PUFA-ω3;••3 products contained glutathione••39 products contained vitamin A orβ-carotene.As mentioned above, patients may currentlychoose from about 100 preparations; however, letus restrict our considerations to the 73 preparationsthat were analyzed in detail by the author.When purchasing a product, the patient mustmake a choice, and thus, what factors should thepatient be guided by when making this choice?Using the simplest exclusion criteria, such aspresence of vitamin A or β-carotene, symbolicdose (< 1 mg) of lutein, lack of details regardingthe source/quantity of macular pigments, or thepresence of ineffective compounds, such as glutathione,at most 20 out of the total of 73 preparationsmay be selected. When applying additionalcriteria (e.g. the seniority and importance of themanufacturer in the drug and/or dietary supplementmarket), the number of products that couldbe recommended to patients would not exceed10. However, for an individual patient who wouldlike to purchase an inexpensive but “good” product,10 products is simply 9 too many!The trend to enrich the OAP-type supplementswith PUFA-ω3 has already been mentioned.Manufacturers of such “combination” supplementsargue that they provide AMD patientswith everything they need in a single capsule!Another, more convincing arguments (comparedto the “everything you need in one” message,as mentioned above) are arriving from thenearly completed Age-Related Eye Disease Study2 (AREDS-2), which, contrary to the AREDS-1(or simply AREDS) study, test the use of macular10 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 11 – 16pigments and PUFA-ω3 in AMD patients. Itshould be mentioned that the AREDS study is amulticenter, 5-year clinical study conducted inmore than 3,000 patients. The objective of thestudy was to assess the effect of high doses ofantioxidants (these included vitamin C, vitaminE and β-carotene) and zinc on the progression ofAMD. As shown by the published reports, thetested AREDS formula did not inhibit vision loss,although it had some beneficial effects reducingthe risk of further development of AMD. Authorsof the promising article titled “New approachesand potential treatments for dry age-related maculardegeneration”, published in 2012, make referenceto the AREDS study reports of 2001 andthe Erratum of 2008 — report as follows: “theAREDS formula does not prevent GA [geographicatrophy] from forming or progressing” [40].AREDS-2 (ClinicalTrials.gov; Identifier NTC00345176; sponsored by National Eye Institute(NEI) with collaboration from National Heart,Lung, and Blood Institute – NHLBI), is, similarlyto AREDS, a 5-to-6-year (2007–December 2012),multicenter (82 clinical centers in the UnitedStates), randomized clinical study to evaluate theeffect of oral supplementation with macular xanthophylls(lutein, zeaxanthin) and omega-3 polyunsaturatedacids (PUFA-ω3) (DHA, EPA) onAMD progression. Below is the list of agents testedin AREDS (AREDS-1) and AREDS-2 studies:Jerzy Z. Nowak: Age-related macular degeneration (AMD): a critical appraisal …retinoids may act as substrates for formation ofphotocytotoxic bis-retinoids. Beneficial effectsof zinc have been known for a long time, andthere was no need for another detailed verificationof its advantages. However, a question arosewith regard to the dose — it would be better if thelower dose (25, not 80 mg) was efficient. As far asthe PUFA-ω3 doses used in AREDS-2 study areconcerned, the author agrees with the total doseof 1 g, although he is not certain whether 650 mgof EPA and 350 of DHA is a good dose ratio (1.86)for AMD patients. Considering the role of DHAin the photoreceptors–RPE cells complex [3], onemight expect a higher dose of DHA (possibly atthe cost of a lower amount of EPA).Combination preparations (“all in one”: macularpigments, microelements, PUFA-ω3) may beconvenient for patients; however, the manufacturersare well aware that the presence of reasonableamounts of PUFA-ω3 in capsules requiresenlarged capsule size, which is not always associatedwith greater convenience of use. One gramof PUFA-ω3 (as used in AREDS-2) takes up aconsiderable volume, thus a “combination” capsulecontaining such an amount should be appropriatelylarge. When trying to adhere to the trendof administering one capsule of a dietary supplementper day, the capsule should contain “daily”doses of all ingredients which would obviously betranslated into capsule size.AREDS-1: vitamin C — 500 mg, vitamin E — 400IU, beta-carotene — 15 mg, zinc (as zinc oxide) — 25and 80 mg, copper (as cupric oxide) — 2 mg;AREDS-2: lutein — 10 mg, zeaxanthin — 2 mg, vitaminC — 500 mg, vitamin E — 400 IU, copper (as cupricoxide) — 2 mg, EPA – 650 mg, DHA – 350 mg.Smaller studies (Secondary RandomizationAgents — AREDS-Type Supplement) were alsoconducted to examine the effects of zinc (aszinc oxide) at doses of 25 and 80 mg, with particularfocus on the lower dose, and eliminationof β-carotene form the AREDS formula.Of note is the lack of beta-carotene and zinc inthe Primary Randomization Agents of AREDS-2study. As shown by the alpha-tocopherol, betacarotenecancer prevention study (ATBC), betacarotenecontributes to the development of lungcancer in smokers [41]; in addition, beta-caroteneis a precursor of vitamin A, and the visual cyclehttp://military.isl-journals.comHowever, there is one argument that does notsupport combining PUFA-ω3 with the remainingingredients in preparations recommended toAMD patients. AMD patients are usually at anadvanced age, and PUFA-ω3 are often recommendedto them also by physicians of other (nonophthalmological)specializations. For example,cardiologists and psychiatrists (as well as otherphysicians, although these two specializationsare predominant) nearly routinely recommendPUFA-ω3-rich dietary supplements at daily dosesthat often exceed 1 g. Facing different trade namesof various “cardiologic”, “psychiatric” and “ophthalmic”dietary supplements, patients may beunaware that they actually take the same chemicalentities! And all these entities are accumulated inthe same system! Therefore, it might happen thata patient would take not 1, but 2, and perhaps 3or more grams of PUFA-ω3 per day while beingunaware of this fact! Taking such scenario intoconsideration, one should not forget preparations11

© Military Pharmacy and Medicine • 2012 • 4 • 12 – 16which contain antioxidants and microelementsseparately from PUFA-ω3, and which could betaken by the patient in line with the overall pictureof his ailments and treatment.It should be mentioned that many national andworldwide medical organizations (including theWHO) recommend daily intake of EPA and DHAin total amounts of 400–600 mg/day, while certainguidelines mention the dose of 1 g/day, andthe European Food Safety Authority (EFSA) holdsthe position that there is no scientifically supportedrecommended daily dose of PUFA-ω3 forhumans. However, EFSA recommends the DHAdose of 100 mg/day in infants, on the premise thatDHA contributes to the development and functionalmaturation of vision system; EFSA also recommendsa daily dose of ca. 250 mg (EPA + DHA)to children and adolescents aged 2-18 years [4] .On the other hand, a statement published in2010 by the French Safe Food Agency (AFSSA,currently MSNA — National Agency for Drugsand Health Products) recommends a daily doseof ca. 500 mg of EPA and DHA combined as apreventive measure in AMD patients. As seenfrom the presented data, the recommended dailydoses of PUFA-ω3 are diverse, cover a wide rangeof 100–1000 mg and depend on the patient’s ageand health status.What’s interesting, in case of cardiovascular conditions[5] , the recommended dosage of omega-3 fatty[4] By request of the European Commission, the EFSA Panel on Dietetic Products, Nutrition andAllergies (NDA) performed an analysis and issued a scientific opinion regarding acceptablemaximum daily intake of long-chain PUFA-ω3, i.e. EPA, DHA and DPA in humans. A studyentitled “Scientific opinion on the tolerable upper intake level of eicosapentaenoic acid(EPA), docosahexaenoic acid DHA) and docosapentaenoic acid (DPA)” was published in therecent issue of EFSA Journal [2012; 10(7): 2815]. In final conclusions, one reads: “The Panelconcludes that the available data are not sufficient to establish a tolerable upper intake levelfor n-3 LCPUFA (DHA, EPA, and DPA, individually or combined) for any population group. ThePanel considers that supplemental intakes of EPA and DHA combined at doses up to 5 g/day,and supplemental intakes of EPA alone up to 1.8 g/day, do not raise safety concerns for theadult population. The Panel also considers supplemental intakes of DHA alone up to 1 g/daydo not raise safety concerns for the general population. No data are available for DPA whenconsumed alone. The Panel notes that in the majority of the human studies considered, fishoils, which also contained DPA in generally unknown (but relatively low) amounts, were thesource of EPA and DHA.”[5] According to the European and American Heart Associations (EHA, AHA), all patientswith a history of myocardial infarction and patients with stable coronary disease shouldtake PUFA-ω3 at the dose of 1 g per day. According to AHA, supplementation using omega-3acids should not be associated with rigorous elimination of omega-6 acids (e.g. linoleic acid,C18:2-ω6, which accounts for 85-90% of dietary omega-6 acids) which cannot be synthesizedby human body and which, according to numerous opinion-forming sources, including theWHO, should account for 3-10% of daily energy demand. An interesting preparation thatmeets the AHA recommendations (although its omega-3 acid content is relatively small)is the “EYE Q capsules” preparation by a Swiss company Vifor SA distributed in Poland byQpharma; the product contains EPA and DHA (marine fish oil) and primrose oil (omega-6).Review articleacids (EPA + DHA + DPA) may be two-, three-,or even four times higher than the usually recommendedmaximum doses. When taken to reducethe triglyceride levels in hypertriglyceridemia, therecommended dose of PUFA-ω3 (with or withoutstatin or fibrate) may be up to 3-4 g per day.Regardless whether macular pigments andPUFA-ω3 are supplied together or as separatepreparations, below are the daily dose ranges (tobe contained in one capsule taken once daily orin two capsules taken twice a day) of the majoringredients of “ophthalmic” dietary supplementswhich, according to the author of this article,should be beneficial for AMD patients:••Lutein — 10–12 mg••Zeaxanthin — 1–2 mg••Vitamin E — 30–60 mg••Vitamin C — 60–250 mg••Zinc — 10–20 mg••PUFA-ω3 — 500–800 mg (overall, withDHA ≥ EPA)Optionally: meso-zeaxanthin (up to 10 mg),copper, selenium, manganese.The doses or dose ranges listed above are relativeand refer to both the compositions of productsavailable at Polish market and the experimentaland clinical data published on the topic.Products containing PUFA-ω3 should necessarilycontain vitamin E. The author’s opinion isthat there is no need to expand the compositionof an ophthalmic preparation by ingredients,e.g. vitamins, other than these listed above. Theaddition of meso-zeaxanthin, a macular pigmentcharacterized by potency equal to that ofzeaxanthin, may be beneficial for patients. Acomment should also be made with regard tothe content of lycopene, which is not discussedin this article. Although lycopene is not a macularpigment, it is worth to remember its role,as it is involved in repair of the three oxycarotenoids(lutein, zeaxanthin, meso-zeaxanthin)after they react with free radicals. Lycopene is acarotene featuring 11 conjugated double bonds,abundantly present in tomatoes. [6]With regard to the PUFA-ω3 content and DHAto EPA ratio in supplement preparations, the[6] For more information on lycopene in patients with AMD see Nowak, Wiktorowska-Owczarek, “AMD, Stargardt’s disease, and carotenoids as components of ophthalmicantioxidant preparations used in AMD” (Mag Lek Okul. 2012; 6(4): 185-98).12 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 13 – 16Jerzy Z. Nowak: Age-related macular degeneration (AMD): a critical appraisal …author is aware of four products available inPoland, in which the DHA dose is larger thanthat of EPA. This makes the products worth mentioning— they include:••Ocuvite Reti-NAT forte (Bausch&Lomb); 1capsule contains: 900 mg of fish oil, including540 mg PUFA-ω3 – 420 mg DHA and 120 mgEPA — ratio 3.5; 1 capsule per day (the producthas been withdrawn from the market by themanufacturer; perhaps some physicians stillretained some supplies);••Omega 3 (Ophtagen); 1 capsule contains: 500mg of fish oil, including 250 mg DHA and 85mg EPA (ratio 2.94), 1-3 capsules per day;••MaxiVision Total (ASA); 1 capsule contains:500 mg of fish oil, including 250 mg DHA and34.6 mg EPA (ratio 7.22), 1 capsule per day;and••Ocuvite Complete (Bausch&Lomb); 1 capsulecontains (according to information on thepackaging): 421.5 mg of fish oil, including 175mg DHA (no information on the content ofEPA), 2 capsules per day. [7]While the two first preparations contain fish oiland no macular pigments (i.e. they are focusedon PUFA-ω3), compositions of the two remainingproducts include also macular pigments,vitamins and minerals. MaxiVision Total — 20%lutein extract (corresponding to 20 mg of lutein),1 mg of zeaxanthin, vitamins E and C, zinc andselenium; Ocuvite Complete — lutein 5 mg, zeaxanthin1 mg, vitamins E and C, and zinc.Ocuvite Reti-NAT forte contains definitely thelargest amount of DHA (420 mg compared to 250mg in MaxiVision and Omega-3 and ca. 175 mg inOcuvite Complete), while the DHA to EPA ratio inindividual supplements is as follows: 7.22 (MaxiVision),7.19 (Ocuvite Complete), 3.50 (Ocuvite Reti-Nat) and 2.94 (Omega-3). The author is curious withregard to the origin of the fish oil in MaxiVision[7] Ocuvite Complete has only recently been introduced to the Polish market of dietarysupplements and probably replaced similar products offered by Bausch&Lomb beforeits introduction. The product does not feature an accompanying leaflet, and relevantdata on its composition are provided on the packaging. According to the informationavailable for the user, the composition of the supplement is as follows (the presentedvalues refer to two capsules recommended as a daily dose): fish oil 843 mg, including350 mg DHA, vitamin C 180 mg, vitamin E 30 mg, zinc (as zinc sulfate) 15 mg, lutein 10mg, zeaxanthin 2 mg (macular pigments originate from Tagetes erecta flower extract);no EPA content is provided. However, the Polish supplier of the product has madeavailable more detailed data on the content of PUFA-ω3. According to these data, 1capsule of Ocuvite Complete contains 421.71 mg of fish oil, including: 181.5 mg ofDHA-TG (corresponding to 174.4 mg DHA) and 25.3 mg EPA-TG (24.3 mg EPA); thus, theDHA to EPA ratio is 7.19.http://military.isl-journals.comTotal and Ocuvite Complete products, characterizedby such high DHA to EPA ratios — no relevantinformation is provided for Ocuvite Complete,while the information leaflet to MaxiVision Total,which also does not provide this information, mentionsthat „The unsaturated omega-3 fatty acids(DHA, EPA) in MaxiVision Total are derived froma high grade fish oil…”, which is perhaps imprecise,but nonetheless reassuring.As mentioned before in case of properly profileddiet, also pharmaceutical supplementation may, butdoes not have to help the AMD patients. The potentialhelpful effects might be suggested by the recentlypublished experimental and clinical studies, whichwere quite numerous in recent years [24–28, 38].Also the results of the AREDS-2 studies, whichshould be published starting from 2013 [8] , shouldbe — or so it seems — suggestive in this matter.While browsing the published data, there is nomissing the fact that results presented in moststudies are not definitely convincing (at least, notto the author of the article), although they sometimesmeet the threshold of statistical significance.More detailed analysis of these data leadsto conclusion that further studies and clinicalobservations are required to assess the clinicalefficacy of dietary supplements in general, andophthalmic preparations in particular. However,one should not cease being optimistic; optimismshould be cherished by both the physicians whenrecommending appropriate dietary supplementsto patients, and patients who would be regularlytaking it; otherwise, the supplementation wouldserve no purpose whatsoever.As a concluding remark, it should be stated thatwhen deciding to use dietary supplements, AMDpatients should nonetheless remember to adhereto proper diet, including, in addition to selectedfruits and vegetables, at least one (or better yet,two) high-fat marine fish meals per week.Acknowledgments:Article funded byMedical University of Lodz within the statutoryactivity (503/1-023-01/503-01).[8] On 26 July, 2012, the first report from the AREDS-2 studies, titled: „The age-related eyedisease study 2 (AREDS2): study design and baseline characteristics (AREDS2 Report number 1)”– Ophthalmology 2012 Nov; 119(11): 2282-9, presenting the study design and basiccharacteristics of the project was published as an e-pub in PubMed database.13

© Military Pharmacy and Medicine • 2012 • 4 • 14 – 16References:Review article1. Nowak JZ: [Dry form AMD – do we know how totreat it?]. Mag Lek Okul. 2011; 5: 44–8.2. Nowak JZ: [Ophthalmic antioxidantpreparations: a survey and supportive argumentsfor their use in AMD]. Mag Lek Okul. 2010; 4:185–98.3. Nowak JZ: [Omega-3 polyunsaturated fatty acidsin retina and medical practice – pros and cons].Mag Lek Okul. 2009; 3: 208–20.4. Nowak JZ: Age-related macular degeneration(AMD): pathogenesis and therapy. PharmacolRep. 2006; 58: 353–63.5. Nowak JZ: [In search of biomarkers for agerelatedmacular degeneration (AMD)]. Mag LekOkul. 2009; 3: 132–43.6. Nowak JZ: [Role of lipofuscin in pathogenesisof age-related macular degeneration (AMD)].Magazyn Okulistyczny. 2005, 2: 103–14.7. Nowak JZ: [Drusens, basal deposits, inflammationand age-related macular degeneration(AMD)]. Magazyn Okulistyczny. 2005; 2: 174–86.8. Nowak JZ: [Inflammation: acute, chronic andpara-inflammation – new ideas, new drugs]. MagLek Okul. 2011; 5: 194–211.9. Bhutto I, Lutty G: Understanding age-relatedmacular degeneration (AMD): relationshipsbetween the photoreceptor/retinal pigmentepithelium/Bruch’s membrane/choriocapillariscomplex. Mol Aspects Med. (2012); 33: 295-317.10. Fine SL, Berger JW, Maguire MG, Ho AC: Agerelatedmacular degeneration. N Engl J Med.2000; 342: 483–92.11. McConnell V, Silvestri G: Age-related maculardegeneration. Ulster Med J. 2005; 74: 82–92.12. Klaska I, Nowak JZ: [The role of complement inphysiology and pathology]. Post Hig Med Dosw(Online). 2007; 61: 167–77.13. Anderson DH, Radeke MJ, Gallo NB, ChapinEA, Johnson PT, Curletti CR et al.: The pivotalrole of the complement system in aging andage-related macular degeneration: hypothesis revisited.Prog Retin Eye Res. 2010; 29: 95–112.14. Wiktorowska-Owczarek A, Nowak JZ: [AMDand oxidative stress. 1. The analysis of factorsinfluencing the generation of reactive oxygenspecies in the retina]. Mag Lek Okul. 2008; 2:200–4.15. Wiktorowska-Owczarek A, Nowak JZ: [Luteinand zeaxanthin – two carotenoids serving theprotection against age-related macular degeneration(AMD)]. Okulistyka. 2004; 7: 29–34.16. Wiktorowska-Owczarek A, Nowak JZ: [AMDand oxidative stress. 2. The analysis of componentsof pharmaceutical preparations used inprophylaxis of AMD]. Mag Lek Okul. 2008; 2:205–12.17. Wiktorowska-Owczarek A, Nowak JZ: [Pathogenesisand prophylaxis of AMD: focus on oxidativestress and antioxidants]. Postepy Hig MedDosw (online). 2010; 64: 333–43.18. Nowak JZ: [Age-related macular degenerationand immunological system: how muchimmunology is in AMD?]. Mag Lek Okul. 2009;3: 102–14.19. Khoo HE, Prasad KN, Kong KW, Jiang Y, IsmailA: Carotenoids and their isomers: color pigmentsin fruits and vegetables. Molecules. 2011; 16:1710–38.20. Sommerburg O, Keunen JE, Bird AC, van KuijkFJ: Fruits and vegetables that are sources forlutein and zeaxanthin: the macular pigment inhuman eyes. Br J Ophthalmol. 1998; 82: 907–10.21. Nebeling LC, Forman MR, Graubard BI, SnyderRA: Changes in carotenoid intake in the UnitedStates: the 1987 and 1992 National HealthInterview Surveys. J Am Diet Assoc. 1997; 97:991–6.22. Nebeling LC, Forman MR, Graubard BI, SnyderRA: The impact of lifestyle characteristics oncarotenoid intake in the United States: the 1987National Health Interview Survey. Am J PublicHealth. 1997; 87: 268–71.23. Nowak JZ, Koszela K: [Eylea TM (VEGF-Trap-Eye) – New „antiVEGF” drug: therapeuticapplications and significance for the Avastin-Lucentis dilemma]. Mag Lek Okul. 2011; 5:324–36.24. Loane E, Kelliher C, Beatty S, Nolan JM: Therationale and evidence base for a protective roleof macular pigment in age-related maculopathy.Br J Ophthalmol. 2008; 92: 1163–8.25. Bone RA, Landrum JT, Mayne ST, Gomez CM,Tibor SE, Twaroska EE: Macular pigment indonor eyes with and without AMD: a casecontrolstudy. Invest Ophthalmol Vis Sci. 2001;42: 235–40.26. Bernstein PS, Zhao DY, Wintch SW, Ermakov IV,McClane RW, Gellermann W: Resonance Ramanmeasurement of macular carotenoids in normalsubjects and in age-related macular degenerationpatients. Ophthalmology. 2002; 109: 1780–7.27. Obana A, Hiramitsu T, Gohto Y, Ohira A,Mizuno S, Hirano T et al.: Macular carotenoidlevels of normal subjects and age-relatedmaculopathy patients in a Japanese population.Ophthalmology. 2008; 115: 147–57.28. Sabour-Pickett S, Nolan JM, Loughman J,Beatty S: A review of the evidence germaneto the putative protective role of themacular carotenoids for age-related maculardegeneration. Mol Nutr Food Res. 2011; 55: 1-17.29. Sabour-Pickett S, Nolan JM, Loughman J,Beatty S: A review of the evidence germaneto the putative protective role of themacular carotenoids for age-related maculardegeneration. Mol Nutr Food Res. 2012; 56:270–86.30. Kanis MJ, Berendschot TT, van Norren D: Influenceof macular pigment and melanin on inci-14 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 15 – 16dent early AMD in a white population. GraefesArch Clin Exp Ophthalmol. 2007; 245: 767–73.31. Jahn C, Wüstemeyer H, Brinkmann C, TrautmannS, Mössner A, Wolf S: Macular pigmentdensity in age-related maculopathy. Graefes ArchClin Exp Ophthalmol. 2005; 243: 222–7.32. Berendschot TT, Willemse-Assink JJ, BastiaanseM, de Jong PT, van Norren D: Macular pigmentand melanin in age-related maculopathy in ageneral population. Invest Ophthalmol Vis Sci.2002; 43: 1928–32.33. LaRowe TL, Mares JA, Snodderly DM, KleinML, Wooten BR, Chappell R; CAREDS MacularPigment Study Group: Macular pigment densityand age-related maculopathy in the Carotenoidsin Age-Related Eye Disease Study. An ancillarystudy of the women’s health initiative. Ophthalmology.2008; 115: 876–83.34. Dietzel M, Zeimer M, Heimes B, Claes B, PauleikhoffD, Hense HW: Determinants of macularpigment optical density and its relation to agerelatedmaculopathy: results from the MuensterAging and Retina Study (MARS). Invest OphthalmolVis Sci. 2011; 52: 3452–7.35. Burke JD, Curran-Celentano J, Wenzel AJ: Dietand serum carotenoid concentrations affectmacular pigment optical density in adults 45years and older. J Nutr. 2005; 135: 1208–14.36. Trieschmann M, Heimes B, Hense HW, PauleikhoffD: Macular pigment optical density measurementin autofluorescence imaging: comparisonof one – and two-wavelength methods.Jerzy Z. Nowak: Age-related macular degeneration (AMD): a critical appraisal …Graefes Arch Clin Exp Ophthalmol. 2006; 244:1565–74.37. Trieschmann M, Beatty S, Nolan JM, HenseHW, Heimes B, Austermann U et al.: Changesin macular pigment optical density and serumconcentrations of its constituent carotenoids followingsupplemental lutein and zeaxanthin: theLUNA study. Exp Eye Res. 2007; 84: 718–28.38. Delyfer MN, Buaud B, Korobelnik JF, RougierMB, Schalch W, Etheve S et al.: Association ofmacular pigment density with plasma ω-3 fattyacids: the PIMAVOSA study. Invest OphthalmolVis Sci. 2012; 53: 1204–10.39. Ma L, Yan SF, Huang YM, Lu XR, Qian F, PangHL et al.: Effect of Lutein and Zeaxanthin onMacular Pigment and Visual Function in Patientswith Early Age-Related Macular Degeneration.Ophthalmology. 2012; 119: 2290-7.40. Evans JR, Lawrenson JG: Antioxidant vitaminand mineral supplements for preventing age-relatedmacular degeneration. Cochrane DatabaseSyst Rev. 2012; 6: CD000253.41. Damico FM, Gasparin F, Scolari MR, Pedral LS,Takahashi BS: New approaches and potentialtreatments for dry age-related macular degeneration.Arq Bras Oftalmol. 2012; 75: 71–6.42. Albanes D, Heinonen OP, Taylor PR, VirtamoJ, Edwards BK, Rautalahti M et al.: Alpha-Tocopherol and beta-carotene supplements andlung cancer incidence in the alpha-tocopherol,beta-carotene cancer prevention study: effects ofbase-line characteristics and study compliance. JNatl Cancer Inst. 1996; 88: 1560–70.http://military.isl-journals.com15

© Military Pharmacy and Medicine • 2012 • 4 • 17 – 20Jerzy Bertrandt at al.: Assessment of the energy expenditure of soldiers of …PhysiologyAssessment of the energy expenditure of soldiers of theRepresentative Battalion of the Polish Army during three daysof drill training as part of preparations for the celebration of theNational Independence Day of November 11 thJerzy Bertrandt, Anna Kłos, Roman Łakomy1Department of Hygiene and Physiology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland.Author’s address:Jerzy Bertrandt, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland; phone:(+48) 22 685 31 34, 601 853 117, e–mail: J.Bertrandt@wihe.waw.pl.Received: 2012.09.27 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Introduction: The main mission of the Representative Battalion of the Polish Army consists of statelyrepresentation of the Polish Army during state celebrations, various state and military holidays or patrioticand religious events, as well as performing representative tasks at the Presidential Residence or duringofficial visits hosted by the Prime Minister.Aim of the work: The objective of this study was to assess the energy expenditure of soldiers during athree-day grill training as part of preparations for the celebration of the National Independence Day ofNovember 11 th .Methods: The measurements were made on the basis of systolic heart rate as recorded by Polar SportTester 810 pulse meters. The energy expenditure was calculated from the relationship between the systolicheart rate and oxygen consumption.Result: The mean energy expenditure of tested soldiers was 4.93±1.59 kcal/min.Conclusion: Energy expenditure of soldiers during 7 hours of effective drill training as part of preparationsfor the celebration of the National Independence Day of November 11th was different and allowedthe workload to be classified as light to very heavy.Key words: energy expenditure, Representative Battalion of the Polish Army, military service.IntroductionCurrent history of the representative units of thePolish Army dates back to 1944. In that year, onSeptember 14 th , the first post-war Warsaw GarrisonHeadquarters was established in the Pragadistrict. The headquarters fulfilled representativeand garrison tasks which were later taken over bythe Warsaw Garrison Command.As a result of organizational changes in thestructure of units under the Warsaw Garrisonhttp://military.isl-journals.comCommand, the Capital City of Warsaw GarrisonHeadquarters, including representativesubunits, was disbanded as of December 31 st ,2000. The representative tasks were taken overby the Representative Battalion of the PolishArmy. The new unit became operative as of January1 st , 2001. The newly formed unit consistedof three Representative Companies of the PolishArmy, the Polish Armed Forces RepresentativeBand, a salute platoon, a protection companyand staff. Starting from January 1 st , 2009, the17

© Military Pharmacy and Medicine • 2012 • 4 • 18 – 20Battalion comprises also a Cavalry Squadron ofPolish Armed Forces as a mounted representativesubunit.The main mission of the battalion consists ofstately representation of the Polish Army duringstate celebrations, various state and military holidaysor patriotic and religious events, as well asperforming representative tasks at the PresidentialResidence or during official visits hosted bythe Prime Minister [1].Every year, soldiers of the battalion provideceremonial setting to ca. 1200 events, mainlystate, military, or patriotic and religious celebrationsboth home and abroad, as well as performthe guard of honour duties at the Tomb of theUnknown Soldier and the Presidential Palace.Representative Battalion soldiers are well-knownfor their mastery of parade drill, presented tomuch acclaim during state and military holidays,band festivals or other events.The objective of this study was to assess theenergy expenditure of soldiers during a threedaydrill training as part of preparations for thecelebration of the National Independence Day ofNovember 11 th .Material and methodsThe study was conducted in 22 soldiers servingin the Representative Battalion of the PolishArmy The energy expenditure was measuredover three days of intense drill trainingtaking up 8 hours per day. The measurementswere made on the basis of systolic heart rate asrecorded by Polar Sport Tester 810 pulse meters.The energy expenditure was calculated from therelationship between the systolic heart rate andoxygen consumption. The energy expenditurewas measured in soldiers performing differentceremonial tasks under weather conditionsconsisting of the air temperature of 7–9 °C anddrizzle precipitation.ResultsThe average age of the tested soldiers was 25.3±2.5y,ranging from 22 to 31 years. Mean height of thesoldiers was 182.7±3.7 cm (176-191 cm), whilemean body weight was 87.9±7.5 kg (67-101 kg).Original articleTable 1: Energy expenditure during preparations to theNational Independence Day of November 11 th .Subjectno.Energy expenditurekcal/minHeart rateMinimum Maximum Mean1 3.013 80 180 1042 3.105 52 142 803 3.122 59 121 844 3.454 60 144 865 3.665 53 132 846 3.689 69 145 877 3.830 55 177 1188 3.852 57 161 899 3.872 45 225 9110 3.938 47 161 11811 4.036 83 163 11112 4.676 69 148 9413 5.191 68 159 9614 5.359 63 160 9715 5.510 65 158 9816 5.848 68 159 10217 5.924 70 208 10218 6.647 81 161 10519 6.551 64 222 10220 6.928 83 173 10721 7.465 79 227 11122 8.711 86 176 114Mean: 4.93±1.59 66.1±12.1 168.2±29.1 99.1±11.4The energy expenditure during preparations tothe National Independence Day of November 11 this presented in Table 1.Mean energy expenditure in subjects was 4.93±1.59kcal/min. Depending on the ceremonial activitybeing trained, the energy expenditure ranged from3.013 kcal to 8.711 kcal/min. According to Christensen’sclassification of workload, the measuredmean energy expenditure associated with theactivities performed by the soldiers of the RepresentativeBattalion of the Polish Army as partof preparations to the celebration of the NationalIndependence Day of November 11th allows theworkload to be classified as light [2]. Also indicativeof light workload is the mean systolic heartrate of 99.1±11.4 bpm [3]. During the three-dayconcentration, the training sessions were held for8 hours/day, with the effective drill training timeof 7 hours. Mean energy expenditure of soldiers18 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 19 – 20during a 7-hour training was 2068.9±671.2kcal, with actual values ranging from 1265.5to 3658.6 kcal depending on the activity performed.Although according to the classificationof workload depending on the energyexpenditure per labour shift, can be classified asheavy on the basis of mean energy expenditure[4], the actual values of energy expenditure werediverse and depended on the type of ceremonialactivities performed. As shown by the obtainedresults, work performed by some soldiers wasclassified as light, while energy expenditure ofothers was typical for heavy, or even very heavyworkloads. The results of earlier studies of theJerzy Bertrandt at al.: Assessment of the energy expenditure of soldiers of …energy burden of soldiers of the RepresentativeCompany of the Polish Army suggested that thedaily energy expenditure was 4,648 kcal, whichclassified the work performed by the soldiers asvery heavy [5].ConclusionThe energy burden of the soldiers of the RepresentativeBattalion of the Polish Army during thedrill training held as part of preparation for thecelebration of the National Independence Day ofNovember 11 th was varied and allowed the workloadto be classified as light to very heavy.References:1. www.brepr.wp.mil.pl2. Christensen C.G., Frey H.M., Foenstelinen E. A.: Acritical evaluation of energy expenditure estimatesbased on individual O2 consumption/heart ratecurves and average daily heart rate. Am. J. Clin. Nutr.1983, 37, 468-4723. Klonowicz S.: Wybrane zagadnienia fizjologii pracyw: J. Rosner Ergonomia. Zagadnienia przystosowaniapracy do człowieka. Warszawa, 1974, 139.4. Bugajska J.: Ocena obciążenia pracą fizycznądynamiczną na stanowisku pracy. Pakiet edukacyjny„Nauka o pracy – bezpieczeństwo, higiena,ergonomia”. CIOP, www.cop.pl5. Kłos A., Szymański A.: Ocena wydatkuenergetycznego młodych mężczyzn pełniących służbęwojskową w Kompanii Reprezentacyjnej WP, LekarzWojskowy 1996, 9-10, 522-525http://military.isl-journals.com19

© Military Pharmacy and Medicine • 2012 • 4 • 21 – 26Jaśmina Żwirska at al.: Assessment of microbial quality of drinks not included …EpidemiologyAssessment of microbial quality of drinks not included in thehospital diet as consumed by patients during hospitalizationand the assessment of microbial contamination of hospital airJaśmina Żwirska 1 , Wanda Jabłońska 1 , Paweł Jagielski 1 , Stanisław Stępniewski 2 ,Małgorzata Schlegel Zawadzka 11Department of Human Nutrition, Institute of Public Health, Jagiellonian University Medical College,Krakow, Poland2St. Louis Voivodship Specialist Pediatric Hospital in Krakow, PolandAuthor’s address:Jaśmina Żwirska, Department of Human Nutrition, Institute of Public Health, Jagiellonian University MedicalCollege, ul. Grzegórzecka 20, 31-531 Krakow, Poland; phone: (+48) 426393270,e–mail: jzwirska@cm-uj.krakow.plReceived: 2012.10.18 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Introduction: According to epidemiological data from different countries, the incidence of nutritionrelatedpoisonings and infections is constant, and even growing in some regions. Currently, there areno standards defining acceptable levels of airborne microorganisms in indoor air (hospital facilities)in PolandMaterial and methods: 100 juice samples collected from previously opened packagings between March2007 and December 2009 in the Voivodship Specialist Hospital in Krakow were subjected to microbialexamination. Open juice packagings were kept for 48 hours at room temperature in patient rooms atthe hospital wards. Ninety-one air quality measurements were also conducted at different locations inthe hospital to monitor microbial infections. The control group consisted of 50 juice samples stored inhome conditions.Conclusions: Significant transgression of the acceptable air contamination limits in hospital rooms,together with the transgressed limits of microbial contamination in juices suggest that the juices mightbe a potential source of nosocomial infections. Opened juices should not be stored at room temperaturefor periods longer than 24 h.Key words: microbial contamination, juices, air, nosocomial infections.IntroductionAccording to epidemiological data from differentcountries, the incidence of nutrition-relatedintoxications and infections is constant, andeven growing in some regions. In the past, juiceswere excluded from food safety studies due totheir low pH values resulting from the presencehttp://military.isl-journals.comof organic acids with antibacterial properties.However, recent studies suggested a possibilityof food poisoning induced by contaminatedjuices [1-3].Intestinal infections occurring in differentgroups of patients during hospitalization may21

© Military Pharmacy and Medicine • 2012 • 4 • 22 – 26be not only due to patient-to-patient transmission,but also to the consumption of food ofpoor microbial quality. The threat may originatemainly from products brought to patientsby visitors [1]. It is common for the visitors tobring drinks in large packagings, both cartonand plastic bottles. Patients, particularly childrenand the elderly, have difficulties usingsuch packagings. This also pertains to patientswho cannot move easily after procedures theyunderwent. With water consumption recommendationssuggesting that a single servingshould not exceed ca. 100 mL (in adults), depletionof a 1.5 L, or sometimes even a 2 L takes asignificant amount of time [4]. This poses a significantthreat of microbial infection with bacteria,fungi and molds present in the hospitalenvironment [5].Currently, there are no standards definingacceptable levels of airborne microorganismsin indoor air (hospital facilities) in Poland TheOrdinance of the Minister of Health of 26 June2012 on detailed requirements for the facilitiesand equipments in entities engaged in medicalactivities, being the executive act for the Actof 15 April 2011 on medical activities (Journal ofLaws of 2011, No. 112 item 654) contains only oneparagraph regarding air quality. Paragraph 37 ofSection 6 of the Ordinance, titled System requirementsreads that In operating, theaters, isolationwards and immunocompromised patient rooms,ventilation systems should be used that ensure airquality parameters suited to the function of thesefacilities. There are no numerical values indicatingair quality assessments [6,7].French standard NF S 90-351: 2003 classifies thefacilities into 4 infection risk zones. The standard’sguidelines classify corridors, elevators,staircases, waiting rooms, physician’s officesaccessible to outpatients, rehabilitation rooms,pregnancy wards, facilities for patients requiringlong or medium hospitalization periods, mentalhealth care facilities, central sterilization facilities(washing zones), drugstores, laundries and toiletsas zone 2 facilities. According to the authors ofthe guidelines, zone 2 is a medium risk level zone[8]. Of highest interest to microbiologists is thequality of air in operating rooms [9-11]. Studiesin residential facilities may provide basis to comparisonsof conditions in the areas where patientsare staying.Original articleThe study of hazardous factors published by J.L.Górny in 2004, which included standards, recommendationsand proposed acceptable levelfully illustrates the vastness of public healthissues which have to be considered, includingissues regarding patients staying at healthcarefacilities [15].No studies of the contaminating effect of hospitalair on food brought to patients’ rooms andconsumed by patients were found in the availableliterature. Thus, fruit juices were selectedfor analysis, as they are the drinks that are mostcommonly consumed by both children andadults staying in hospital facilities (unpublisheddata from own observations).The objective of the study was to evaluate themicrobial risks for hospitalized patients in relationto juices brought to the hospital by visitors.Material and methodsThe study took place in one of the VoivodshipSpecialist Hospitals in Krakow. Selection ofjuices followed an analysis of consumption patternsin patients staying in patient rooms andsurveys regarding the frequency of drink consumption(unpublished data from own observations).A total of 100 juice samples werecollected for microbial analysis from previouslyopened carton, glass or plastic packagingsbetween March 2007 and December 2009.Opened juices were stored in patient rooms for48 hours at room temperature. Ninety-one airquality measurements were also conducted atdifferent locations in the hospital to monitormicrobial infections.The control group consisted of 50 juice samplesstored in home conditions. Microbial quantitativeanalysis of juices was performed by theKoch’s plate dilution method. Bacterial countswere performed after 72 h of incubation at 37 ° C.Air samples were collected for microbial analysesusing a MAS-100 Microbial Air Monitoring Systemby MERCK. The system automatically sampleda pre-defined volume of air into the instrumenthead containing a sterile single-use Petri dish withagar medium suitable for tested microbial groups.Following solid selective media were used for quantitativedeterminations of microorganisms:22 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 23 – 26Jaśmina Żwirska at al.: Assessment of microbial quality of drinks not included …1) Total bacterial count — Columbia agarmedium.2) Staphylococci — Chapman ager medium.3) Gram-negative rods — MacConkey agar.4) Fungi — Sabourand agar medium.Petri dishes with air samples and selective culturemedia were incubated in appropriate conditions.The results of analyses were compared to relevantstandards and literature data.Results and discussionMicrobial contamination of foods (includingdrinks) may be due to both improper pasteurizationprocess, and to contamination with pathogenicbacteria after pasteurization. As mentionedbefore, large-size juice packagings purchased byvisitors are commonly found in patient rooms.They are usually stored at patients’ beds. Microbialpurity of these juices may be doubtful, particularlyafter a prolonged time of storage at roomtemperature. Food safety monitoring proceduresmight reduce hospitalization costs as well as toTable 1: Number of pathogenic bacteria and fungi in juices.Samplingsiten(%)Pathogenic bacteria(Columbia agar medium)http://military.isl-journals.compotentially allow to avoid e.g. nosocomial infectiousdiarrhea, which is a factor that prolongshospitalization of children [16,17].Of all biological risk factors, bacteria and moldsare characterized by the furthest range of allergicand toxic effects. They are also emitted withdust into the air, which might lead to chronicorgan diseases, such as respiratory or gastrointestinaldiseases [18].Microbial evaluation of juice samples collectedat hospitals revealed the total bacterial countstandard limits being exceeded in 56% of samples.Fungal count standard limits were exceededin 23% of samples. Evaluation of control samplesrevealed the total bacterial count standard limitsbeing exceeded in 21 cases (42%), with theremaining samples being within limits. Fungalcount standard limits were exceeded in 5 (10%)control samples (Table 1).In 26 cases, juices standing at patients’ bedsideswere not contaminated with either bacteria orfungi. Statistical analysis revealed that comparedPathogenic fungi(Sabourand agar medium)None 0 < ..< Normal Above normal None 0 < ..< Normal Above normal28(28)16(16)X±SD - 70.92±44.6*56(56)151,467.5±307,313.8*HospitalN=10064(64)13(13)- 55.5±54.8*23(23)261,929.7±345,018.2*Median - 71.25 9,875 - 45 72,000Minimum - 10 280 - 1 600Maximum - 155 1,724,000 - 158 1,280,000n(%)23(46)6(12)X±SD - 89.2±56.9**Control — private housesN=5021(42)44,438.6±191,496.2**39(78)6(12)- 35.0±52.8**5(10)318,572.6±537,984.4**Median - 85 2,023 - 13 146Minimum - 10 350 - 2 2,733Maximum - 155 880,000 - 140 1,250,000n – number of samples, X±SD - arithmetic mean ± standard deviation; * ,** statistically significant differences between groups.PN-A-79034 Non-carbonated soft drinks. Bacterial counts determined after 72 h of incubation not larger than 200 per 1 mL.Mold content per 1 mL: unacceptable.Yeast counts not larger than 200 per 1 mL [19].23

© Military Pharmacy and Medicine • 2012 • 4 • 25 – 26Jaśmina Żwirska at al.: Assessment of microbial quality of drinks not included …Bacterial culturesFigure 1: Total number of bacteria in the hospital air(Columbia agar medium).Figure 3: Total number of fungi in a juice sample(Sabourand agar medium).ConclusionsTransgression of acceptable limits of air purity inhospital rooms, as well as of the microbial contaminationof juices, is alarming.Significant transgression of the acceptable aircontamination limits in hospital rooms, togetherwith the transgressed limits of microbial contaminationin juices suggest that the juices mightbe a potential source of nosocomial infections.Figure 2: Total number of staphylococci in the hospital air(Chapman agar medium).Opened juices should not be stored at room temperaturefor periods longer than 24 h.References:1. Windyga B, Ścieżyńska H, Grochowska A et al.: Ocenazagrożeń zdrowotnych wynikająca z zanieczyszczeniażywności drobnoustrojami chorobotwórczymi.Bromat Chem Toksykol Supl, 2003; 36: 281-284.2. Visser H, Verhoef L, Schop W et al.: Outbreakinvestigation in two groups of coach passengerswith gastroenteritis returning from Germany to theNetherlands in February 2009. Euro Surveill,2010; 15(28).pii: 19615.3. Noel H, Hofhuis A, De Jonge R et al.: Consumptionof fresh fruit juice: how a healthy food practicecaused a national outbreak of Salmonella Panamagastroenteritis. Foodborne Pathog Dis,2010; 7(4): 375-381.4. Jarosz M, Bułhak-Jachymczyk B: Normy żywieniaczłowieka. Podstawy prewencji otyłości i choróbniezakaźnych. PZWL Warsaw, 2008.5. Charkowska A: Czystość mikrobiologiczna ipyłowa środowiska szpitalnego (cz. II). ChłodnictKlimatyz, 2006; 2: 28 (http://archiwum.chlodnictwoiklimatyzacja. pl/artykuly/2006_02/28.htm Accessed on: 20.11.2012).6. Ordinance of the Minister of Health of 26 June2012 on detailed requirements for the facilities andequipments in entities engaged in medical activities.7. Act of 15 April 2011 on medical activities. Journal of.Laws 2011 no. 112 item 654.8. NF S 90-531 standard for healthcare centers in France(http://www.armstrong.pl/assets/global/commclgeu/flash/healthcare-01-2011/pl/pdf/PL_NORMA%20NF%20S%2090-351%20DLA%20PLACOWEK%20SLUZBY%20ZDROWIA%20WE%20FRANCJI.pdfAccesed on: 20.11.2012)9. Charkowska A: Jakość i czystość powietrzawewnętrznego w salach operacyjnych w szpitalach.Educational Meeting at the Chief SanitaryInspectorate, Warsaw 8.12.2011 r. (http://www.gis.gov.pl/ckfinder/userfiles/files/Departament%20Higieny%20%C5%9Arodowiska/Wydzia%C5%82%20ds%20Nadzoru%20Sanitarnego/Nadz%C3%B3r%20Zapobiegawczy/Anna%20Charkowska%20-%20Wyk%C5%82ad%20szpitale%202011%20cz%C4%99%C5%9B%C4%87%201.pdfAccessed on: 20.11.2012).http://military.isl-journals.com25

© Military Pharmacy and Medicine • 2012 • 4 • 26 – 2610. Gregorowicz-Warpas D, Pałubicka A, Wolski A,Kaiser K: Czyste powietrze w salach operacyjnych.Materiały szkoleniowe dla pielęgniarekepidemiologicznych. Zesz. IV, Wrocław 2005.11. Napoli C, Marcotrigiano V, Montagna MT:Air sampling procedures to evaluate microbialcontamination: a comparison between active andpassive methods in operating theatres. BMC PublicHealth, 2012; 12:594 doi: 10.1186/1471-2458-12-594.12. Rokitka H, Krajewska-Kułak E, Szepietowski J et al.:Analiza występowania grzybów w pomieszczeniachbloku operacyjnego. Mikol Lek, 2006; 13(4): 301-305.13. Krajewska-Kułak E, Łukaszuk C, Gniadek A et al.:Zanieczyszczenie powietrza w pomieszczeniachmieszkalnych, ze szczególnym uwzględnieniem roligrzybów. Mikol Lek, 2011; 18(3): 135-139.14. Krogulski A: Metody oznaczania ogólnej liczbybakterii w powietrzu atmosferycznym i wewnątrzpomieszczeń. Roczn PZH, 2006; 57(1): 1-7.15. Górny RL: Biologiczne czynniki szkodliwe: normy,zalecenia i propozycje wartości dopuszczalnych.Podstawy i Metody Środów Pracy,2004; 3(41): 17-39.16. Abushelaibi AA, Sofos NJ, Samelis J et al.: Survivaland growth of Salmonella in reconstituted infantcereal hydrated with water, milk or apple juice andstored at 4º C, 15º C and 25º C. Food Microbiol, 2003;20: 17-25.17. Neuhoff–Murawska J, Socha P, Socha J: Soki: zalety izagrożenia w żywieniu dzieci i młodzieży. Stand Med,2007; 4: 91-99.Original article18. Sadowski T, Czuba Z, Król W: Mikrobiologicznaocena produktów żywnościowych w magazynachszpitalnych. Zdr Publ, 2006; 116(3): 512-514.19. Napoje bezalkoholowe niegazowane wraz ze zmianami.PN-A-79034/A1: 1997 — z wyłączeniem p. 5.1.20. Krzysztofik B: Mikrobiologia powietrza. Wyd. PolitechnikiWarszawskiej, Warszawa 1992.21. Czyżanowska J, Bulanda M: Czynniki ryzyka zakażeńszpitalnych u dzieci. Pediatr Pol, 2007; 11: 873-878.22. Krogulski A: Lokalizacja szpitali a czystość mikrobiologicznapowietrza w pomieszczeniach. Roczn PZH,2008; 59: 97-102.23. Krogulski A: Czystość mikrobiologiczna powietrza saloperacyjnych – wybrane aspekty. Roczn PZH,2006; 57: 277-282.24. WHO Guidelines for indoor dampness and mould.Executive Summary. WHO, Copenhagen Danmark,2009.25. Łukaszuk C, Krajewska–Kułak E, Wrońska I et al.:Badania powietrza w oddziałach onkologicznych wBiałymstoku i Lublinie. Onkol Pol,2002; 5(3-4): 147-152.26. Krogulski A., Szczotko M.: Czystość mikrobiologicznapowietrza w szpitalach. Sale operacyjne klimatyzowane.Roczn PZH, 2010; 61(4): 425-429.26 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 27 – 32Justyna Kołodziejska at al.: Cholesterol oxyethyleneation products as …Pharmacology & PharmacyCholesterol oxyethyleneation products as modifiers of theabsorption base in anti-inflammatory ointmentsJustyna Kołodziejska 1 , Marian Mikołaj Zgoda 1 ,Katarzyna Ejzenchart 1 , Magdalena Piechota-Urbańska 21Chair of Applied Pharmacy, Department of Drug Formulation Technology, Medical University of Lodz, Poland2Chair of Applied Pharmacy, Department of Retail Pharmacy,Medical University of Lodz, PolandAuthor’s address:Justyna Kołodziejska, Chair of Applied Pharmacy, Department of Drug Formulation Technology, MedicalUniversity of Lodz, ul. J. Muszyńskiego 1, 90-151 Lódź, Poland; e–mail: jkolodziejska0730@wp.plReceived: 2012.10.08 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Introduction: The assumption behind the study was to attempt modification of pharmacopoeial anhydrousabsorption base, i.e. hydrophilic vaseline, by the addition of novel cholesterol oxyethyleneationproducts. Novel base with variant compositions was proposed as a carrier for ketoprofen – a medicinalsubstance with analgesic, anti-inflammatory and antipyretic activity.Material and methods: 5 model ointments were prepared with the absorption base consisting of hydrophilicvaseline modified with cholesterol oxyethyleneation products. Extensometric method was usedto test spreadness of the preparations, gravimetric method to determine the rate of volatile componentsloss, while viscosity parameters were determined with cone-plate digital rheometer. The test for ketoprofenpharmaceutical availability was performed with spectrophotometric method.Results: Modification of the absorption base (hydrophilic vaseline) by introduction of novel cholesteroloxyethyleneation products increased the extensibility parameters of all prepared ointments. Viscositytests showed that all hydrophilic vaseline-based ointments with variant compositions were tixothropicand rheologically unstable. Introduction of cholesterol derivatives into the formulae of hydrophilicvaseline-based ointments reduces their structural viscosity values. Comparison of the areas under thecurves of the release of ketoprofen lysinate showed that the active substance was best released from ointmentswith cholesterol oxyethylenates with the lowest n umber of segments (n TE ), regardless of the typeof the catalyst used to produce these oxyethylenates (M-Ch-10 Na and M-Ch-10 Ca).Conclusions: As shown by the conducted studies, the use of novel oxyethylate-containing productsaffects optimization of the rheological parameters of the ointments and the efficacy of the release ofketoprofen lysinate into a model recipient fluid.Key words: ointments, skin inflammation, hydrophilic vaseline, cholesterol oxyethyleneation products.IntroductionThe objective of rheological studies in drug formulationtechnology is to determine correlationsbetween structure-related physicochemicalproperties of the drugs and the usabilityhttp://military.isl-journals.comof these drugs [1,2,3]. Rheological parametersof topical pharmaceuticals, such as ointments,creams, gels, or pastes, are determined bycomponents included in the base [4]. Appropriateselection of these components impacts27

© Military Pharmacy and Medicine • 2012 • 4 • 28 – 32pharmaceutical availability of medicinal substances,and thus the efficacy of treatment.The assumption behind the study was to attemptmodification of pharmacopoeial anhydrousabsorption base, i.e. hydrophilic vaseline, by theaddition of novel cholesterol oxyethyleneationproducts manufactured by the Surface ActiveAgents Production Plant ICSO Blachownia inKędzierzyn-Koźle [5,6,7]. The novel base withvariant compositions was proposed as a carrier forketoprofen — a medicinal substance with analgesic,anti-inflammatory and antipyretic activity [8].The main indications for local application ofketoprofen include muscle and joint pains,inflammatory conditions caused by injuries suchas joint dislocations, sprains or sports injuries,and tendonitis [9]. Local administration of ketoprofendetermines its activity in pathological tissuesand minimizes the risks of adverse eventsreported for oral use [10].ObjectivesThe goal of the study was to assess the effects ofcholesterol oxyethyleneation products on rheologicalparameters of hydrophilic vaseline-basedointments and the efficacy of the release of a nonsteroidalanti-inflammatory drug available aslysinate salt into the external compartment.Reagents and equipmentReagents:••hydrophilic vaseline (Coel);••ketoprofen lysinate (Sigma);••cholesterol oxyethyleneation products containingthe following numbers of oxyethylenicsegments (n TE ); 10, 20, 30, 40 (productsmanufacture using a sodium catalyst) and 10for calcium catalyst (Surface Active AgentsProduction Plant ICSO Blachownia inKędzierzyn-Koźle);••distilled water.Instrumentation:••MR 200 formulation mixer (Alpina);••water bath MLL 147/6 AJL (Electronic Krakow,Poland);••Cone/plate DV-III digital rheometer, version3.0 (Brookfield);••bath thermostat PGW E1 (Medingen);Original article••extensometer, pH-meter N5170E with ERH-131electrode (Hydromet Gliwice, Poland);••drug release apparatus Erweka DT 600(Erweka), apparatus accd. to Mutimer et al.;••Visking Dialysis Tubing C/100 membrane,wall thickness 74 μm and pore diameter 75 μm(Serva Electrophoresis GmbH);••spectrophotometer Nicolet Evolution 300,version 1.0 (Spectro-Lab);••technical balance (Radwag, PrecisionMechanics Plant in Radom, Poland), analyticalbalance (Radwag, Precision MechanicsPlant in Radom, Poland).Experimental methodDevelopment of model formulae5 model ointments were prepared with theabsorption base consisting of hydrophilic vaselinemodified with cholesterol oxyethyleneationproducts. The formula of the ointments is presentedin Table 1.Table 1: Formula of the ointments with the absorptionbase consisting of hydrophilic vaseline modifiedwith cholesterol oxyethyleneation products.IngredientKetoprofen lysinateHydrophilic vaselineCholesterol oxyethyleneation product *Distilled waterQuantity (g)2.576.51.020.0* Oxyethyleneation products used included products prepared using a sodiumcatalyst had the following numbers of oxyethylenic segments: n TE=10 (M-Ch-10 Naointment), n TE=20 (M-Ch-20 ointment), n TE=30 (M-Ch-30 Na ointment), n TE=40(M-Ch-40 Na ointment) and the product of n TE=10, prepared using a calcium catalyst(M-Ch-10 Ca ointment).For comparison, an ointment containing no cholesteroloxyethyleneation products was also prepared(M-0 ointment). The formula of the ointmentsis presented in Table 2.Table 2: The formula of the ointments with hydrophilicvaseline base.IngredientKetoprofen lysinateHydrophilic vaselineDistilled waterQuantity (g)2.577.520.0Ointment extensibility testThe test was conducted at 25 °C using the extensometricmethod.28 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 29 – 32Justyna Kołodziejska at al.: Cholesterol oxyethyleneation products as …Determination of ointment viscosity parametersOintment viscosity tests were conducted at32 °C±0.1 °C using a cone/plate digital rheometercoupled with a bath thermostat [12].Determination of the kinetics of the loss of volatileointment componentsPlates with the diameter of d=9cm and totalsurface area of P=63.59 cm2 were covered withuniform ointment layers. Thus prepared sampleswere placed in a dryer-balance at 32±0.1 °C for2.5 and the percentage weight loss readings weretaken every 15 minutes.Determination of the kinetics of the release of lysinatefrom the ointmentThe test was conducted using the technique usedfor transdermal therapeutic systems according toPh.Eur. 6 requirements [13].Figure 1: The relationship between the applied load and the observedincrease in M-Ch-30 Na ointment surface area.Figure 2 compares the extensibilities of all testedointments under the highest load applied duringthe test (227 g).A 5 g ointment sample was placed in a dialysiscontainer with the mass exchange surfaceP=19.625 cm 2 (apparatus accd. to Mutimer etal.). Next, the ointment surface was covered byan appropriately prepared Visking dialysis membrane.Before the test, the dialysis membrane wasexposed to distilled water over 24 h. The entiresystem was closed with the lid and tightened withnuts. Thus prepared dialysis container was placedin a thermostated vessel (32°±0.1 °C), containing0.25 dm 3 of distilled water as a recipient liquid.The solution above the container was put in continuousrotational motion using a stirrer rotatingat 100 rpm. The mass exchange rate was measuredby spectrophotometric analysis of ketoprofenlysinate released from the ointment. Measurementswere made at nine time points over 6hours (samples collected at 40-minute intervals).The amount of the released ketoprofen lysinatewas determined at λ=260 nm using the followingequation: A= 0.4249·c+ 0.0677 (r=0.9991), where:A is absorbance and c is the concentration of thepharmaceutical substance.Results and DiscussionResults of extensometric testsExtensometric tests (measurements of extensibility)allowed to assess products’ capacity toincrease its surface area under the pressure force.Figure 1 presents an example extensibility curve(relationship between the extended ointmentsurface area and the force load applied).http://military.isl-journals.comFigure 2: Comparison of extensibilities of all tested ointmentsunder the highest load applied during the extensometrictest.Extensibility is the measure of product’s capacityto increase its surface area under increasingpressure force. Products of high extensibility areeasily distributed over the administration site.This affects the quality of application. Administrationof ointments on inflamed tissues shouldnot increase the pain sensation. Good extensibilityof the ointment increases the rate of release ofthe active substance at the site of administration.Diffusion of the active substance into the externalcompartment may occur over a large ointmentsurface area that has been spread using alow pressure force.Modification of the absorption base (hydrophilicvaseline) by introduction of novel cholesterol oxyethyleneationproducts increased the extensibilityparameters of all prepared ointments (Fig. 2).In case of ointments prepared using novel ointments,and in case of the highest loads appliedduring the extensometric tests, the surface areasof extended ointments ranged from: 3.61 to 4.52c.u. In case of the ointment with unmodified formula(M-0), the value was 3.15 c.u.29

© Military Pharmacy and Medicine • 2012 • 4 • 30 – 32Viscosity test resultsFigure 3: Hysteresis loop for the M-0 ointment.Ascending curveDescending curveOriginal articlewere performed by increasing the shear rate fromzero to a pre-defined maximum value and thanback to zero immediately after reaching the maximumpoint. Figures 3 and 4 present examplehysteresis loops obtained for the M-0 ointmentand for an ointment containing a cholesteroloxyethyleneation product (M-Ch-10 Na).Positive tixotrophy was observed for all preparedproducts. Upon isothermal flow of the fluid thathas previously been in stasis for a prolonged time,the shear stress was reversibly reduced over timein these systems.Structural viscosity of the tested ointments wascompared at the ascending hysteresis loop curvefragments for three arbitrarily selected shearrates of 12.2, 24.2 and 30.2 1/s. The results arelisted in Table 3.Figure 4: Hysteresis loop for the M-Ch-10 Na ointment.Ascending curveDescending curveViscosity tests showed that all hydrophilic vaseline-basedointments with variant compositionswere tixothropic and rheologically unstable, asconfirmed by the hysteresis loop test [14]. Measurementsof shear stress depending on shear rateTable 3: Structural viscosity parameters for the model ointments.OintmentShear rate12.2 1/sShearstress[N/m2]Viscosity[mPa·s]Shear rate24.2 1/sShearstressViscosity[N/m[mPa·s]2 ]Shear rate30.2 1/sShearstress[N/m 2]30 http://military.isl-journals.comIntroduction of cholesterol derivatives into theformulae of hydrophilic vaseline-based ointmentsreduces their structural viscosity values,as observed at all three shear rates tested in thestudy. Based on the Einstein-Smoluchowskiequation: D=kT/6πrη, (where: D — diffusivityof the medicinal substance, k — Boltzmann constant,T — temperature in Kelvins, r — observedradius of the molecule of the medicinal substance,η — viscosity) [15], one may expect that thereduction in viscosity parameters wouldenhance diffusibility of the medicinal substance(ketoprofen lysinate) from the ointmentinto the external compartment, which isassociated with increased anti-inflammatoryefficacy of the product.Viscosity[mPa·s]M-0 52.5 4286 49.7 2054 50.5 1672M-Ch-10NaM-Ch-20NaM-Ch-30NaM-Ch-40NaM-Ch-10Ca47.5 3895 24.5 1010 23.9 789.942.3 3471 30.4 1257 30.2 99444.1 3618 28.2 1167 29.6 980.852.1 4269 39.2 1618 42.9 142251.1 4188 40.0 1651 38.8 1284Water loss kinetics test resultsThe measurements of water loss kineticsconstitute a supplement to the rheologicaltests (extensibility, structural viscosity). Theointment’s tendency to lose water affects itsstructural viscosity following applicationon the skin, and thus, the kinetics of therelease of the active substance. From thisstandpoint, slight viscosity changes arepreferred over time. The measurements ofthe water loss kinetics may also be used toassess the rheological stability of the productas part of stability tests. Slight changesin the ointment mass occurring over time

© Military Pharmacy and Medicine • 2012 • 4 • 31 – 32affect the stability of its physicochemical parametersupon storage.Figure 5 presents an example curve of ointmentwater loss.Justyna Kołodziejska at al.: Cholesterol oxyethyleneation products as …2152.8 c.u. In case of the ointment with unmodifiedformula (M-0), the value was 1895.5 c.u.(Table 4). As shown by the calculations, the testedointments would be characterized by comparablechanges in viscosity parameters during applicationon the tissue affected by inflammation. Thediffusibility of ketoprofen lysinate would be atsimilar levels throughout the contact with theapplication site, as follows from th e Einstein-Smoluchowski equation (D=kT/6πrη).Results of determination of the kinetics ofthe release of lysinate from the ointmentFigure 5: Kinetics of water loss for the M-Ch-10 Ca ointment.Table 4: Parameters of the regression equation of the typey=ax+b describing the kinetics of the loss ofwater from the ointmentOintmentRegression equationcoefficientsabCorrelationcoefficientrSurfacearea [c.u.]M-0 0.1653 0.4036 0.9916 1895.5Figure 6 presents an example of the relationshipbetween the quantity of the released ketoprofenlysinate (in mg per cm2 of the dialysis membrane)as a function of the square root of time.The obtained relationships were described bycorrelation equations of the types y=ax+b andlg(y)=a·lgx+b (a logarithmic form of the exponentialM-Ch-10 Na 0.1721 0.4951 0.9912 1983.6M-Ch-20 Na 0.1560 0.4693 0.9871 1800.8M-Ch-30 Na 0.1875 0.4776 0.9945 2152.8M-Ch-40 Na 0.1760 0.4549 0.9921 2021.6M-Ch-10 Ca 0.1744 0.4520 0.9927 2003.4The relationship between the loss in the massof the tested ointments [%] and time [min.] wasdescribed at the significance level ofp=0.05 by a regression equation ofthe type y=ax+b. Parameters a andbe were used to calculate the surfaceareas P under the water loss curves,expressed in conventional units [c.u.],using an integration method. Theobtained values are listed in Table 4.It was shown that introduction of cholesteroloxyethyleneation productsinto the ointment formula did not significantlyaffect the loss of water fromthe products. Surface areas under thecurves of the loss of water from theointment containing different cholesterolderivatives ranged from 1800.8 toOintmentM-0M-Ch-10NaM-Ch-20NaM-Ch-30NaM-Ch-40NaM-Ch-10Cahttp://military.isl-journals.comFigure 6: Kinetics of the release of ketoprofen lysinate from theM-Ch-30 Na ointment.Table 5: Regression equations describing the kinetics ofthe release of ketoprofen lysinate from modelointmentsRegressionequationtypey=ax+blg(y)=a·lgx+by=ax+blg(y)=a·lgx+by=ax+blg(y)=a·lgx+by=ax+blg(y)=a·lgx+by=ax+blg(y)=a·lgx+by=ax+blg(y)=a·lgx+bRegression equationcoefficientsab4.1365·10-3 -2,0335·10-20.6435 -1.84175.160·10-31.02525.1299·10-31.63525.4611·10-31.18116.0644·10-31.57585.5206·10-31.4582-0.0451·10-2-2.3003-2.2820·10-2-3.2015-1.0226·10-2-2.5368-2.7472·10-2-3.0646-2.3623·10-2-2.9553Correlationcoefficientr0.97310.96510.97460.96680.99400.99710.99910.99980.98810.99750.98460.9909Surfacearea[c.u.]0.40440.90880.53190.74420.62250.974631

© Military Pharmacy and Medicine • 2012 • 4 • 32 – 32equation y=axb). Regression equations and areasunder the curves of ketoprofen lysinate releaseexpressed in conventional units are listed in Table 5.As shown by the high correlation coefficient forthe linear equation y=ax+b at p=0.05, the processof release of ketoprofen lysinate from theointment follows a zero-order kinetics. The exactkinetic equations based on the analysis of the diffusionprocess are usually complex and have theform of a sum of exponential functions [16].The areas under the curves of release of the activesubstance from cholesterol derivatives-containingointments are larger than the area obtainedfor the ointment obtained from hydrophilic vaselineonly. For the cholesterol derivatives-containingointments, the values ranged from 0.5319 to0.9476, while for the M-0 ointment, the value was0.4044 c.u.Comparison of the areas under the curves of therelease of ketoprofen lysinate showed that theactive substance was best released from ointmentswith cholesterol oxyethylenates with thelowest n umber of segments (n TE ), regardless ofthe type of the catalyst used to produce theseReferences:1. Górecki M: Reologia farmaceutyczna - perspektywyrozwoju. Farm Pol, 1996; 52(16): 739-743.2. Górecki M, Zalewska A: Reometryczna analizafarmaceutycznych układów rozproszonych. Farm Pol,2000; 56(15): 748-752.3. Górecki M, Zalewska A: Reologia farmaceutyczna wanalizowaniu układów nienewtonowskich. Farm Pol,2001; 57(9): 417-419.4. Lee ChH, Moturi V, Lee Y: Thixotropic property inpharmaceutical formulations. J Control Release, 2009;136 (2): 88-98.5. Zgoda MM, Nachajski M, Kołodziejczyk M,Woskowicz M, Lukosek M.: Właściwościsolubilizacyjne i litogenolityczne wodnych roztworówniejonowych związków powierzchniowo aktywnychproduktów oksyetylenowania cholesterolu. PolimMed, 2007; 37(4): 39-57.6. Kołodziejczyk M., Zgoda MM: Oksyetylenowanycholesterol jako składnik modelowych płynówakceptorowych w ocenie dostępności farmaceutycznejliofilowych środków leczniczych. Farm Pol, 2007;63(8): 342-348.7. Kołodziejczyk M, Zgoda MM: Ocena właściwościfizykochemicznych produktów oksyetylenowaniacholesterolu w aspekcie micelarnej solubilizacjiliofilowych środków leczniczych. Pol J Cosmetol,2006; 9(4): 250-263.Original articleoxyethylenates (M-Ch-10 Na and M-Ch-10 Ca).More than a twofold increase in the efficacy ofrelease of ketoprofen lysinate was achieved fromointments containing cholesterol derivativesincluding n TE =10 oxyethylenic fragments.ConclusionsNovel formulae for the ointment base, obtainedafter introducing oxyethyleneated cholesterolderivatives into hydrophilic vaseline may comprisea potential vehiculum for anti-inflammatoryointments. Regardless of their chemical structure(the number of oxyethylenic fragments) and thetype of catalyst used in the synthesis of the oxyethyleneate,its presence in the ointment contributesto the favourable change in rheologicalparameters (increased surface area of extendedointment under pressure force, reduced structuralviscosity with a negligible effect on the effectof the water loss). Introduction of cholesterolderivatives into the hydrophilic vaseline-basedointments enhances the efficacy of the release ofketoprofen lysinate from the ointment. The highestareas under the release curved were obtainedfor products containing cholesterol derivativesfeaturing n=10 oxyethylenic fragments.8. Korzeniowska K, Jankowski J, Jabłecka A:Niesteroidowe leki przeciwzapalne. Farm Współcz,2010; 3: 192-197.9. Sarzi-Puttini P, Atzeni F, Lanata L, Bagnasco M,Colombo M, Fischer F, D'Imporzano M: Pain andketoprofen: What is its role in clinical practice.Reumatismo, 2010; 62(3): 172-178.10. Coaccioli S: Ketoprofen 2,5% gel: a clinical overview.Eur Rev Med Pharmacol Sci, 2011; 15(8): 943-949.11. Samczewska G, Zgoda MM: Solubilizacyjnewłaściwości wodnych roztworów siarczanuneomycyny. Pol J Cosmetol, 2002; 1: 49-63.12. Kołodziejska J: Parametry reologiczne past do zębów adostępność farmaceutyczna jonu fluorkowego. BromatChem Toksykol, 2004; 36 (1): 77-83.13. Zgoda MM., Ogiński M: Przydatność wybranychmembran dializacyjnych do oceny warunkach in vitroprocesu wymiany masy na granicy faz z preparatutypu hydrożel. Pol J Cosmetol, 1999; 3: 197-208.14. Tamburic S: The aging of polimer- stabilized creams:the rheological viewpoint. C&T, 2000; 115(10): 43-49.15. Poradnik fizykochemiczny, Wydawnictwo Naukowo-Techniczne, Warszawa 1974.16. Bodek KH: Badania porównawcze kinetykiuwalniania diklofenaku z hydrożelumikrokrystalicznego chitozanu i hydrofilowej maścifarmakopealnej. Farm Pol, 2000; 56 (15): 753-762.32 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 33 – 50Jerzy Z. Nowak: Non-steroidal anti-inflammatory drugs (NSAIDs) in …OphthalmologyNon-steroidal anti-inflammatory drugs (NSAIDs) inophthalmology: pharmacological and clinical characteristicsJerzy Z. NowakDepartment of Pharmacology, Chair of Pharmacology and Clinical Pharmacology ofMedical University of Lodz, PolandAuthor’s address:Jerzy Z. Nowak, Department of Pharmacology, Medical University, ul. Żeligowskiego 7/9. 90-752 Łódź, Poland;phone: (+48) 42 6393290, e–mail: jerzy.nowak@umed.lodz.plReceived: 2012.10.28 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of inflammation andpain of different origins. Although NSAIDs differ in their structures, their mechanism of action is similar.The therapeutic target of NSAIDs is cyclooxygenase (COX), occurring as two isoenzymes: COX-1(a constitutive enzyme) and COX-2 (an inducible enzyme, expressed in the course of the inflammatoryprocess). Being a component of prostaglandin H synthase (PGHS), COX catalyzes the first step oftransformations of arachidonic acids into prostaglandins (of the D, E and F series), prostacyclin (PGI2)and thromboxanes — all products characterized by diverse biological activities; some of them havingpro-inflammatory action, some being involved in pain mediation. The registered NSAIDs are a numerousfamily of drugs, with vast majority available as products for systemic use (per os, per rectum, intramuscularor intravenous injections) and external use (ointments); only a few products are intended forintraconjunctival administration (ophthalmic products). Active substances used in ophthalmic NSAIDsinclude indomethacin (the active substance in the first ophthalmic drug), suprofen (currently not used),flurbiprofen, pranoprofen, ketorolac, diclofenac, bromfenac and nepafenac. Ophthalmic NSAIDs currentlyavailable in Poland include: Indocollyre (indomethacin; at present rarely used drug), Dicloabak,Difadol 0,1% and Naclof (all containing diclofenac), Yellox (bromfenac) and Nevanac (nepafenac); thetwo latter compounds have only recently become available in Poland. Therapeutic indications may differslightly between individual drugs, but generally they include prevention and treatment of cystoid macularedema after cataract surgery, inhibition of intra-operative miosis during cataract surgery, reductionof pain and photophobia after refractive surgery, and, in addition, treatment of allergic conjunctivitis(mainly ketorolac-containing products). This article provides a critical review of NSAIDs used in medicaltherapy with particular focus on ophthalmic preparations.Key words: Non-steroidal anti-inflammatory drugs, NSAID, ophthalmic preparations,therapeutic indications.IntroductionNon-steroidal anti-inflammatory drugs (NSAID)are popular medications commonly prescribedby physicians and well known to patients. Manyhttp://military.isl-journals.comof such drugs are available without prescription,which contributes to the massive use of suchproducts as aspirin, ibuprofen and paracetamol— a drug closely related to the NSAID family,33

© Military Pharmacy and Medicine • 2012 • 4 • 34 – 50particularly to reduce or relieve pain and fever, aswell as to improve certain less precisely defined ailmentsthat reduce the comfort and quality of life.The progenitor of the NSAID family isacetylsalicylic acid — aspirin, a drug with ahistory of more than 100 years and enormousworldwide popularity. Aspirin was introducedinto the drug market in 1899 and hasbeen extensively used ever since, althoughmany other analgesic, antipyretic and antiinflammatorydrugs have also became availablein that period. The word aspirin contains thestem spir, referring to the Latin term Spireaulmaria, i.e. meadowsweet (modern name isFilipendula ulmaria) — a plant from which theglycoside salicin, characterized by analgesicactivity, was initially obtained. Salicin generatesanalgesic salicylic acid which is transformed byacetylation into acetylsalicylic acid (ASA), i.e.aspirin. The first letter of the word aspirin, i.e.the letter a (preceding the stem, i.e. spir) stoodfor acetylation, while the suffix in was commonlyadded to the drug names at that time.Aspirin’s mechanism of action was elucidatedin early 1970s, when Sir John R. Vane — anEnglish pharmacologist and physician, togetherwhith two Swedish researchers, SuneK. Bergstrom, Bengt I. Samuelsson — discovereda cyclooxygenase-dependent pathway oftransformations of arachidonic acid into prostaglandins(for which they were later awardedthe Nobel Prize in physiology and medicine in1982) [1]. The researchers demonstrated that aspirincauses acetylation of cyclooxygenase andinhibits the synthesis of prostaglandins — endogenousmediators of inflammatory reactions,pain sensation and pathologically elevatedbody temperature. These observations turnedout to have far reaching consequences, as theybecame the point of departure for the researchof other compounds that would inhibit cyclooxygenaseactivity, with hopes that at leastsome of these compounds would become moreefficient and safer than salicylates (includingaspirin), expressing mainly anti-inflammatoryand analgesic activity. This initiated the era ofNSAIDs — ones of the most common drugs intoday’s medical therapy, used mainly in the reliefof pains of various origins and diverse inflammatoryconditions.Review articleThe mechanism of action of NSAIDsAll NSAIDs exert their activity in the processof conversion of arachidonic acid (AA) intoprostaglandin H–PGH 2[2]. This step is catalyzedby prostaglandin H synthase (PGHS), having adual enzymatic activity of cyclooxygenase andperoxidase. The AA → PGH 2conversion consistsof a sequence of two reactions: first, cyclizationof AA into an unstable 15-hydroxyperoxide(PGG 2) followed by double oxidation in positions9-11 by means of the cyclooxygenase componentand next, reduction of the 15-hydroxyperoxidegroup in PGG 2molecule, leading to anequally unstable PGH 2; this step is achieved bymeans of the peroxidase activity of PGHS [1] .Prostaglandin H 2is a substrate for specificsyntha-ses, tissue-dependent isomerases that catalyzeits transformations into various endogenousregulators, such as prostaglandins ofthe D (PGD 2), E (PGE 2), and F (PGF 2) series,prostacyclin (PGI 2) and thromboxanes (TXA 2and TBX 2) — all products characterized by diversebiological activities, with some of them havingpro-inflammatory action (Fig. 1).One should keep in mind that arachidonic acid(AA) is a substrate for many other important,biologically active molecules, to mention only thepro-inflammatory leukotrienes (resulting from AAmolecules undergoing transformation by the activityof lipoxygenase [LOX]) or anti-inflammatory[1] Conversion of arachidonic acid (AA) into prostaglandin H 2 (PGH 2 ) consists oftwo reactions: the first reaction involves an oxygen molecule being incorporatedinto the AA molecule and the resultant structure undergoing cyclization into anunstable prostaglandin G 2 (PGG 2 ), while the other reaction involves reductionof PGG 2 to its 15-hydroxy analog, i.e. PGH 2 . These reactions are catalyzed byprostaglandin H synthase — a bifunctional enzyme exerting both cyclooxygenaseand peroxidase activities. Some textbooks suggest that the cyclooxygenation isachieved by the activity of cyclooxygenase (COX) while peroxidation is achievedby hydroperoxidase (HPOX); however, PGHS is most commonly identified asCOX. Cyclooxygenase was described in 1976, and its amino acid sequence wasdetermined 12 years later. The spatial structure of COX was elucidated as late as inyears 1994–1996 — by that time, it was already known that two isoforms of theenzyme, COX-1 and COX-2, existed, the latter one being inducible by inflammatorystimuli (including pro-inflammatory cytokines such as IL-1β or TNFα). Followingcell activation, COX-2 gene activity reaches its peak value within a dozen or sominutes, and is later reduced to non-determinable levels within one hour. Theactivity of COX-2 increases about 1 hour after the inflammatory stimulus and ismaintained at a high level for several hours after that. The increased activity ofCOX-2 leads to rapid formation of prostaglandins within the pericellular spaceand development of an inflammatory reaction. The main difference in the spatialstructure of the two isoforms COX-1 and COX-2 is that the COX-2 molecule has awider cyclooxygenase activity channel and features a side pocket associated withthe presence of valine instead of isoleucine at position 523 of the COX-2 molecule.Molecules of selective COX-2 antagonists blocking the channels containing theactive sites of the enzyme anchor their side chains in said pocket.34 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 35 – 50Jerzy Z. Nowak: Non-steroidal anti-inflammatory drugs (NSAIDs) in …Figure 1: Metabolizm of arachidonic acid (AA) with the aid of cyclooxygenases (COX) and lipoxygenases (LOX) and sites of actions of nonsteroidalanti-inflammatory drugs (NSAIDs), and glucocorticosteroids in comparison.NSAIDs inhibit COX activity (the COX-1 and COX-2 isoenzymes); depending on the drug the inhibitory effect on COX-1 and COX-2 is varied (COX-1 > COX-2, COX-2 > COX-1). Glucocorticosteroidsinhibit phospholipase A2 – PLA2 (this enzyme releases AA from the pool of membrane phospholipids, which makes the free AA a substrate for COX and LOX).The PLA2-related effect of glucocorticosteroids refers to rapid nongenomic action, which in fact involves an indirect mechanism via lipocortin-1 and EGF receptor-driven signalingpathway. However, the main anti-inflammatory and immunosuppressive effects of glucocorticosteroids, as well as their unwanted effects, result from the specific glucocorticosteroidreceptor-mediated genomic mechanisms involving trans-suppression or inhibition of the expression of genes encoding pro-inflammatory mediators (main therapeutic effect), and transactivation,i.e. stimulation of the expression of genes encoding various proteins with varied biological activity (most of the effects are unwanted).lipoxins (resulting from AA molecules undergoingtransformation by the activity of acetyl-COX-2, i.e.the enzyme acetylated with aspirin, ASA-COX2)[3]. One should also remember that AA is a constantingredient of membrane phospholipids and, in orderto become a substrate for COX, LOX and ASA-COX2it must be extracted from the phospholipid poolinto its free form, which is achieved by means of aspecific phospholipase A 2(PLA 2) enzyme [4]. Thisstep is the stage for anti-inflammatory activity ofglucocorticosteroids, where endogenous cortisol andits synthetic analogs, all of them used in medicine,inhibit the PLA 2activity, blocking the supply of theAA substrate for the synthesis of pro-inflammatorymediators, both COX-dependent (mostlyprostaglandins) and LOX-dependent (leukotrienes)(Fig. 1). It should be highli-ghted that the mainanti-inflammatory effects of glucocorticosteroidsare achieved by means of a receptor-dependentgenomic mechanism as a result of inhibition ofthe expression of genes encoding inflammatorymediators (transsuppression), while the adverseeffects of this class of drugs are due to activation ofthe transactivation mechanism.http://military.isl-journals.comThe findings of the Nobel Prize winners as mentionedin Introduction did not differentiate betweenindividual COX isoforms, as the secondisoenzyme, known as COX-2, was identified onlyas late as in early 1990s [6]. Experiments in dogtissues revealed the existence of a third COX isoform,COX-3, characterized by particular sensitivityto paracetamol. However, as soon becameevident, such paracetamol-sensitive COX-3 isoformis absent from human body, and the humanequivalent of dog COX-3 gene, present in sometissues, particularly the tissues of the centralnervous system (CNS) is an alternatively splicedvariant of COX-1, without preferential sensitivityto paracetamol, encoding a protein with theamino acid sequence different from that of COXand exerting no COX-like activity. Thus, contributionof COX-3 to the mechanism of action ofthe popular drug paracetamol in humans, as proposedby some authors, is not substantiated, asconfirmed by Kis [7] and the recent detailed analysesconducted by Hinz and Brune’s group [8] [2] .[2] The exact mechanism of action of paracetamol is unknown, despite thelong history of its use in pharmacology. Discovered more than 100 years agoand extensively used in medicine for more than half a century, paracetamol35

© Military Pharmacy and Medicine • 2012 • 4 • 36 – 50Review articleBoth COX-1 and COX-2 catalyze the conversionof arachidonic acid (AA) to prostaglandins andthromboxanes, and the difference between them,besides the fact of both isoforms being encodedby separate genes (located at chromosomes 9 and11, respectively) and besides the structural differences(MW 70 kDa and 70-72 kDa; number ofamino acid residues: 599 and 604; 60% homology)consists in the fact that COX-1 is mainly aconstitutive enzyme, i.e. an enzyme that is presentand active all time, while COX-2 is mainlyan inducible enzyme, becoming active in certaincircumstances, e.g. in the course of inflammation.Therapeutic NSAIDs have different affinitiestowards COX-1 and COX-2, which is dueboth to the structural differences between thedrug molecules, and to the structural and conformationaldifferences between the molecules of(synonymous term: acetaminophen) was and remains one of the most commonanalgesic and antipyretic drugs worldwide, available without prescription bothas a single-agent product or combined with other agents. The anti-inflammatoryeffect of paracetamol is assessed as poor or non-existing, and therefore, the drughas never been considered a member of the NSAID family; what’s interesting,however, it has always been and remains discussed together with this class ofdrugs. Some authors define paracetamol as an atypical NSAID. In recent decades,the prevalent opinion was that paracetamol exerted its analgesic and antipyreticeffect via a central mechanism, and that paracetamol’s effect on the activity ofCOX-1 and COX-2, and thus on the synthesis of prostaglandins, is insignificant.Paracetamol was shown not to inhibit the synthesis of prostaglandins in a tissue/cell homogenate, while exerting such effect in functionally efficient cells (seethe comprehensive discussion on the topic in the article by Graham and Scott,2005 [9]). Graham and Scott argued that the analgesic effect of paracetamolmight be centrally-mediated by activation of descending serotonergic pathways;however, the authors add that the principal stage for the action of the drug mightbe the inhibition of prostaglandin synthesis. The authors further ponder on thepossibility of formation of reactive metabolites at the molecular level as a resultof activation of the peroxidase function of COX-2. Such metabolites would lead todegradation/inactivation of glutathione — a co-factor of enzymes involved inthe synthesis of PGE, and thus to inhibition of the synthesis of PGE 2 . The conceptof paracetamol action involving only the central-mediated, COX-dependentmechanisms does not stand the time test [7]; what is, therefore, the mechanismof paracetamol’s action? The beneficial clinical effects of the drug are beyondall doubt, albeit the knowledge regarding the mechanism of its action is stillincomplete. Contribution from the central serotonergic, or even cannabinoidsystem, is suggested in the effects of paracetamol. The role of cerebral vesselendothelium behind the beneficial therapeutic effects of paracetamol withinthe CNS is also suggested. Studies conducted in recent years revealed thatparacetamol has an inhibitory effect on the activity of both COX-1 and COX-2in peripheral tissues, although to a different degree — a stronger effect wasobserved always in relation to COX-2, particularly in vascular endothelial cells.Articles published in years 2006-2012 and discussing the results of the extensivestudies conducted by Hinz and Brune reveal that paracetamol is a preferentialinhibitor of the COX-2 isoenzyme, although its effect is largely dependent on theenvironmental redox status. The opinion held by the German authors is importantenough to require verification in other centers worldwide, as it is not only themechanism of paracetamol’s therapeutic effect is just concerned, but also theincreasingly often-reported cases of intoxication with this drug, particularly ofpronounced hepatotoxicity resulting from overdosage (intake of more than >4g/day), which is not difficult to achieve as numerous paracetamol-containingproducts are available everywhere and prescription-free.36 http://military.isl-journals.comboth enzymes. Active sites of COX molecules (i.e.substrate binding sites and catalytic domains)are slightly different in both isoenzymes — theyare contained in hydrophobic substrate channelsat the core of the enzyme molecule. In COX-2,the substrate channel is larger — more spaciousand more flexible; thus, COX-2 inhibitors mayenter the channel of the COX-2 molecule (wherethey are able to exert their effects), while beingtoo large to enter the COX-1 channel to block thecatalytic center.This fact translates into the biological activityprofiles of the NSAIDs, particularly in thecontext of their adverse effects. This relates obviouslyto the systemic drugs, not local drugsas ophthalmic NSAIDs, as the side effects if extensiveor long-term therapies with the drugs ofthis group are mostly gastrointestinal (includingserious ulceration effects → onset or complicationsof gastric or duodenal ulcers, includinghemorrhage and perforation) or cardiovascular(thrombotic complications in patients with cardiovasculardisorders and atherosclerosis). Thelist of the adverse effects of NSAIDs is longer,albeit it seems to be not of such importance fortopical treatment; therefore, these considerationswill not be pursued in this article, and interestedreaders may find relevant informationin the recently published article by the same author,titled New NSAIDs and modern forms ofanti-inflammatory drugs (Puls Medycyny — educationalissue, 2012).NSAIDs — Characteristicsand classificationThere is a huge number of NSAIDs available atthe market — they include both the original andgeneric products in formulations suitable e.g. fororal (tablets, capsules), intramuscular and intravenous(liquids for injection), or rectal (suppositories)administrations, as well as ophthalmicpreparations (eye drops).According to the latest edition of the Polishlanguageedited guide-book on drugs currentlyavailable in Poland: Leki Współczesnej Terapii[Medications in Modern Therapy] (20 th ed., MedicalTribune 2010), the most numerous NSAIDproducts contain ibuprofen — 77 simple and 12combination products or diclofenac — 66 simpleand 3 combination products; less numerous

© Military Pharmacy and Medicine • 2012 • 4 • 37 – 50are products containing ketoprofen — 26 simpleproducts and 1 combination product. Manyof these drugs are available without prescription.These products are outnumbered only bymedications containing paracetamol. i.e. ananalgesic and antipyretic drug. It is available in92 products, including 39 simple and as muchas 53 combination products, all availablewithout prescription.NSAIDs are a structurally heterogeneous family ofdrugs, spanning from simple chemical structureslike aspirin to complex, often polycyclic structuresof relatively high molecular weights. Such anumerous and diverse family of medications withsimilar therapeutic indications and a wide spectrumof potentially adverse events requires someorder being introduced by means of classificationthat would take into consideration different propertiesof NSAIDs as regards their chemical structuresand biological activity. However, there is nouniform and worldwide classification of NSAIDs.Later on in the article, two most popular classificationswill be presented, based on either the chemicalstructure of drugs, or their affinity to individualcyclooxygenase subtypes. [3] Both classifications areimportant, since understanding of the chemicalstructure and biological role of COX isoenzymesallows the assessment of particular drugs in functionalterms, i.e. from the standpoint of both therapeutic,and potential adverse effects thereof.NSAIDs are classified by their chemical structuresinto four groups of carboxylic acids, enolicacids, naphtyl ketone derivatives and coxibs.Jerzy Z. Nowak: Non-steroidal anti-inflammatory drugs (NSAIDs) in …••acetic acid — e.g. bromfenac, diclofenac,ketorolac, nepafenac, sulindac;••propionic acid — flurbiprofen, suprofen, pranoprofen,flurbiprofen, ibuprofen, ketoprofen,tiaprofenic acid, naproxene;••anthranilic acid — flufenamic acid, mefenamicacid, meclofenamic acid, niflumic acid;••indole — indomethacin, acemetacinEnolic acids include:••Pyrrazolone derivatives, e.g. aminophenazone,phenylbutazone, metamizole (pyralgin),oxyphenbutazone;••Oxicams, e.g. meloxicam, pyroxicam;Naphtyl ketones — e.g. nabumetone.Coxibs — celecoxib (available in Poland undertrade name Celebrex), the only coxib currentlyused in therapy. Other coxibs, available in thedrug market until recently, such as valdecoxib(Bextra by Pfizer; removed in 2005), and lumiracoxib,etoricoxib shared the fate of the first coxibrecalled from the market in 2004, i.e. rofecoxib(Vioxx by Merck) due to their potential cardiovascularadverse effects.When discussing this classification, one shouldalso mention drugs related to NSAIDs, havingthe analgesic and antipyretic activity and devoidof anti-inflammatory effects, such as paracetamol(acetaminophen) and phenacetin (not longerin the pharmacopoeia, previously known as theingredient in popular APC — aspirin/phenacetin/caffeine— tablets), which are the derivativesof 4-aminophenol.Carboxylic acids include the derivatives of:• • salicylic acid — various salicylates and acetylsalicylicacid (aspirin);[3] As on case of other drugs, NSAIDs may also be classified in sequentialgenerations; such classification highlights certain structural innovations orupgrades, which are the effects of researchers’ strive for drugs characterized bybetter safety (in terms of the adverse events profiles) or better bioavailability andpharmacodynamic parameters. The classification of NSAIDs into three generationsis mentioned by some studies on the topic; however, such classification may notreplace either of the two classifications mentioned above. The generation-basedclassification is as follows:1 st generation — drugs that preferentially inhibit COX-1 (COX-1>COX-2) — Vaneet al. group 1 drugs.2 nd generation — drugs relatively selective towards COX-2 (COX-2>COX-1), e.g.etodolac, meloxicam, nabumetone, nimesulide.3 rd generation — coxibs (selective drugs) characterized by >200 times higheraffinity towards COX-2 compared to COX-1.http://military.isl-journals.comThe widely used classification of NSAIDs basedon their affinity to individual COX isoenzymeswas proposed by Vane et al.; it divides all NSAIDsinto 4 groups:1) Drugs that completely inhibit COX-1 andCOX-2 with low selectivity but a pronouncedpreference towards COX-1; e.g.. aspirin(ASA), diclofenac, ibuprofen, indomethacin,naproxen, piroxicam, as well as bromfenac,flurbiprofen, ketorolac, nepafenac, suprofenpranoprofen, fenoprofen.2) Drugs that inhibit COX-2 with a selectivitythat is 5–50 times higher comparedto COX-1, e.g. celecoxib, meloxicam,nimesulide.37

© Military Pharmacy and Medicine • 2012 • 4 • 38 – 503) Drugs that inhibit COX-2 with a selectivitythat is >50 times higher compared to COX-1,e.g. refecoxib (Vioxx, withdrawn frommarket).4) Drugs that are weak inhibitors of both COXisoforms: 5-aminosalicylic acid (known asmesalazine or mesalamine), sodium salicylate,sulfosalazine.The active substances listed above in italics areavailable in both non-ophthalmic and ophthalmicproducts. With regard to the first, i.e.structural classification, of note is the fact thatophthalmic NSAIDs are listed in two groups:acetic acid derivatives, or, more precisely, heteroaryl— and/or phenylacetic acid derivatives(most of the listed compounds, including indomethacinthat contains indole moiety) and arylpropionicacid derivatives (flurbiprofen assodium salt dihydrate). With regard to the secondclassification, based on the effects againstCOX-1 and COX-2, all ophthalmic preparations are inGroup 1, encompassing inhi-bitors of bothisoenzymes, with preference towards COX-1.Ophthalmic NSAIDsCompared to all available NSAIDs, ophthalmicpreparations are a small group of products — currently,only six such products are available atPolish market (according tothe latest ophthalmic drugsguide-book: Pharmindex-Okulistyka [Ophthalmology]2012): Indocollyre containsindomethacin, Dicloabak, Difadol0,1% and Naclof containthe same active substance —diclofenac, while the other twoophthalmic drugs, Nevanacand Yellox contain nepafenacand bromfenac, respectively.Review articlemore [10-12]. In the past, one other compound,fenoprofen, was tested in ophthalmic preclinicaland clinical trials; however, these did not lead tothe drug being registered.Table 1 presents ophthalmic NSAIDs currentlyavailable in Poland, as well as other compoundsof this class available elsewhere in the world.Indomethacin was the first member of the familyof ophthalmic NSAIDs, introduced in the early1980s — it was widely used in ophthalmologicalpractice (and is still available in the Europeanmarket), but it has never been registered by FDAto be sold within the US. Another non-steroidalcompounds included flurbiprofen, suprofen, diclofenacand ketorolac; the therapeutic potentialof these compounds in ophthalmology wasdescribed by Abelson and Sloan in 1994 [13]. Atthat time, the first two of these drugs were usedmostly for prevention of miosis during ocularprocedures, diclofenac was used in the treatmentof post-operative inflammation followingcataract removal, and ketorolac was used totreat itching occurring in the course of seasonalallergic conjunctivitis (SAC). Another ophthalmicNSAIDs contained fenacs — nepafenac andTable 1: Ophthalmic NSAIDs currently available in Polandand other compounds of this class availableelsewhere in the world.Other ophthalmic preparationsare available outsidePoland, including Acular,Acular-LS, Acular-PF, andAcuvail (all containing ketorolac),as well as Ocufen andOcuflur containing flu-rbiprofen;the suprofen—containingproduct Profenal is not usedas a medicinal product any38 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 39 – 50bromfenac which, together with their extensivelystudied and clinically effective (not only in ophthalmology)progenitor, diclofenac, are currentlythe most common drugs in this category.A detailed characteristics of ophthalmic NSAIDsis presented below. The first part discusses drugscurrently available in Poland (Indocollyre, Dicloabak,Difadol 0,1%, Naclof, Nevanac, Yellox),while the second part discusses other ophthalmicNSAIDs — both drugs used in the past (Profenal,fenoprofen) and currently used in other countriesAcular/Acular-LS/Acular-PF/Acuvail andOcufen/Ocuflur, Niflan).Indomethacin1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1Hindol-3-aceticacid [C 19H 16ClNO 4; MW 357.80g/mol] — an indole derivative of acetic acid (Fig. 2).Jerzy Z. Nowak: Non-steroidal anti-inflammatory drugs (NSAIDs) in …Indications and dosage [4] (according to Pharmindex-Okulistyka[Ophthalmology], 2012):the drug is intended for use during ophthalmicprocedures and in post-operative settings tocounteract miosis, as well as an anti-inflammatoryagent after cataract removal procedures orsurgeries of the anterior ocular segment and ananalgesic following photorefractive keratectomyon first days following the procedure.The dosage depends on the objective of treatment:• • prevention of miosis during surgical procedures:4 drops on the day before the procedureand 4 drops 3 h before the procedure;••prevention of inflammatory conditions due tocataract surgeries or surgeries in the anteriorocular segment: 1 drop 4-6x/day, starting 24hours before the procedure and continueduntil complete resolution of the symptoms ofinflammation;••treatment of pain after photorefractive keratectomy:1 drop 4x/day on first days after thesurgery.Figure 2: Chemical structure of indomethacin.In the early 1960s, Hart and Boardman were the firstto demonstrate that indomethacin (code no. MK 615)efficiently reduced joint edemas in patients with activerheumatoid arthritis [14]. Two years later (1965), indomethacinwas approved for marketing by the US FDAand became the first non-steroidal anti-inflammatorydrug available. The mechanism of indomethacin’s action,i.e. inhibition of prostaglandin synthesis — wasdescribed by Ferreira, Moncada and Vane in 1971 [15].Indomethacin was also the first ophthalmic NSAIDavailable, and a review of early initial clinical observationsregarding its efficacy in patients with post-operativecystoid macular edema following lens extractionand retinal detachment surgery was published in1984 [16].Indocollyre (Chauvin/Bausch&Lomb) 0.1%ophthalmic drops (1 mg indomethacin/mL),bottle of 5 mL.http://military.isl-journals.comCurrently, Indocollyre is used less and less commonly,as newer ophthalmic NSAIDs, discussedbelow, have been introduced.Earlier, eye drops with trade names of Indoptoland Chibro-Amuno contained 10-fold higherconcentrations of indomethacin (1%; 10 mg/mL);however, solubility and pH-dependent stabilityare significant problems in the case of this agent.Indomethacin itself is practically insoluble in water(while being soluble in alcohol) and was usedin ophthalmic preparations (eye drops) only assodium or tromethamine salts. Indomethacinundergoes decomposition in alkaline solution,while being only slightly soluble in acidic solutions,precipitating when the pH value drops below6. The drug, formulated as ophthalmic suspensionbuffered at pH of 5.6, was stable in thepresence of polyvinyl alcohol (PVA) or hydroxypropylmethylcellulose(HPMC). Therefore, thelater formulation of the drug (0.1% solution) containedPoloxamer-407 as a solvent. Indomethacin’spenetration of the cornea increases significantly(compared to ophthalmic solutions) whenthe drug has the form of oil-based suspension,and particularly emulsion (the difference being[4] All ophthalmic NSAIDs are intended for intraconjunctival administration — thisinformation shall not be mentioned again when describing the use of individualproducts.39

© Military Pharmacy and Medicine • 2012 • 4 • 40 – 50nearly 4-fold), which, at relatively low pH, assumesthe non-ionized and lipophilic form. LowpH of the aqueous phase (

© Military Pharmacy and Medicine • 2012 • 4 • 41 – 50Ophthalmic diclofenac preparations include:Dicloabak (Thea; bottle of 10 mL), Difadol 0.1%(Polfa Warsaw; bottle of 5 ml), Naclof (Novartis;bottle of 5 mL) — all products contain diclofenacsodium (0.1% ophthalmic drops;1 mg/mL).Dicloabak does contain no preservatives (it isdistributed in a multi-dose bottle with 0.2 μmfilter membrane to protect contamination uponuse); the remaining two products, i.e. Difadol 0.1%and Naclof contain the preservative — benzalkoniumchloride.Other substances present in the aforementioneddrugs: Dicloabak — castor oil, tromethamine(also known as tromethamol or Tris, i.e. tris(hydroxymethyl) aminomethane), boric acid;Difadol 0.1% — polysorbate-80, boric acid, borax;Naclof — polyoxyethylenated castor oil-35, tromethamine,boric acid, sorbic acid (2 mg/mL),sodium edetate (1 mg/mL) — composition identicalto that of Voltaren Ophthalmic.Indications (accd. toPharmindex — Okulistyka, 2012):Dicloabak — inhibition of miosis during cataractsurgeries prevention of inflammation in thesurgeries of cataract and anterior ocular segment;relief of ocular pain due to photorefractivekeratectomy within 24 hours after the procedure.Difadol 0.1% — inflammation following cataractsurgery or other surgical procedures; fightingsymptoms of eye pain and photophobia, inhibitionof miosis in the course of cataract surgery,prevention of cystoid macular edema followingcataract surgery with lens implantation.Naclof — post-operative inflammatory conditionsafter removal of cataract and other surgicalprocedures, prevention of cystoid macular edemafollowing cataract surgery with lens implantation,post-traumatic inflammation in injuries withoutperforation of the eyeball; inhibition of miosis,fighting symptoms of eye pain and photophobia.Although the three aforementioned productsslightly differ in formal therapeutic indications,there are no rational premises capable of shakingan opinion that the three compounds can be usedinterchangeably, as they are practically identical.Jerzy Z. Nowak: Non-steroidal anti-inflammatory drugs (NSAIDs) in …Dicloabac:••Inhibition of miosis during cataract surgeryand prevention of inflammation in cataractsurgeries and the surgeries of the anteriorocular segment: before surgery — 1 drop up to5x within 3 h before the surgery; after surgery— 1 drop 3x immediately after surgery, andnext 1 drop 3-5x/day, for as long as required.••Fighting ocular pain in photorefractive keratectomywithin the first 24 h after the surgery:before surgery — 2 drops within 1 h beforesurgery; after surgery — 2 drops within 1 hafter the surgery followed by 4 drops within24 h after the surgery.Difadol 0,1%:••Ocular surgery and complications: before asurgical procedure — 1 drop 5x within 3 h;after surgical procedure — 1 drop 3x duringthe surgery and then 1 drop 3-5x per day, foras long as required.••Pain and photophobia: 1 drop every 4-6 h.••Prevention of pain associated with surgicalprocedures — 1-2 drops within 1 h before theprocedure, 1-2 drops within 15 min. after theprocedure and then 1 drop every 4-6 hoursover the following 3 days.Naclof:••Ocular surgery and complications: before asurgical procedure — 1 drop 5x within 3 h;after surgical procedure — 1 drop 3x duringthe day after the surgery and 1 drop 3-5x perday over the following days, for as long asrequired.••Pain and photophobia: 1 drop every 4-6 h.••Pain resulting from surgical procedures — 1-2drops within 1 h before the surgery, 1-2 dropswithin 15 min after the surgery and 1 every4-6 h over 3 days after the surgery.As in the case of therapeutic indications of theaforementioned drugs, which should be identicaldue to the similarity of products, also thedosage of individual products in particular situationsshould be identical. Diverse summariesof therapeutic indications and dosage results inintroduction of unnecessary confusion, implyingthat the products are used for different purposes,which is not true.Dosage (accd. toPharmindex — Okulistyka, 2012):http://military.isl-journals.comAs mentioned above, diclofenac is the originalproduct by Ciba-Geigy (currently Novartis),41

© Military Pharmacy and Medicine • 2012 • 4 • 42 – 50registered under the trade name Voltaren, usedin numerous products containing this active substancefor different uses. Voltaren Ophthalmic orVoltaren Ophthalmic Solution is an ophthalmicproduct very popular in the US, while its equivalentin Poland (and other countries, including theCentral/Eastern European countries) is Naclof.The dosage of the American product is as follows:cataract removal — 24 h after the surgery — 1 dropof the solution 4x a day for a 2-week post-operativeperiod; refractive surgery — 1 drop of the drug onehour before the procedure and 1 drop 15 minutesafter the surgery, followed by 1 drop 4x a day for3 days. The differences in the recommended dosageof Voltaren 0.1% ophthalmic solution andits sibling product Naclof remain the manufacturer’ssecret.Nepafenac2-amino-3-benzoylbenzeneacetamide or 2-amino-3-benzoylphenylacetamide (nepafenac or amfenacamide;pro-drug) [C 15H 14N 2O 2; MW 254,28 g/mol]→ 2-amino-3-benzoylbenzeneacetic or 2-amino-3-benzoylphenylacetic acid (amfenac; the active agent)[C 15H 13NO 3; MW 255.27 g/mol] — a derivative ofphenylacetic (arylacetic) acid (Fig. 4).Nevanac (Nepafenac ophthalmic suspension;Alcon):••is a 0.1% suspension containing nepafenac(1 mg/mL) as the active ingredient; in addition,the product composition includesa preservative — benzalkonium chloride(0.05 mg/mL = 0.005%) and ingredients consideredto be inactive, e.g. mannitol, carbomer974P, tyloxapol (a non-ionic surfactant),disodium edetate. The pH of the solution is7.4 and the osmolarity is 305 mOsmol/kg.Following intraconjunctival administration,nepafenac quickly penetrates through thecornea and is hydrolyzed into the active formof amfenac, reaching the peak concentrationin the aqueous humor after 1 hour [20].Indications (accd. toPharmindex-Okulistyka, 2012):prevention and treatment of post-operative painand inflammation associated with surgicalcataract removal; reduction of the risk of postopera-tivemacular edema associated withsurgical cata-ract removal in diabetic patients.Review articleDosage:••Prevention and treatment of post-operativepain and inflammation associated with surgicalcataract removal — 1 drop 3x/day. Theproduct is first applied on the day before theprocedure, continued on the day of the procedureand for up to a 21-day post-operativeperiod, or up to as much as 60 days in diabeticpatients, as recommended by the physician.Additional drop of the drug should be administered30-120 minutes before the procedure.••Reduction of the risk of post-operativemacular edema associated with surgicalcataract removal in diabetic patients — 1drop 3x/day starting from the day before thesurgical cataract removal, continued on theday of the procedure and for up to a 21-daypost-operative period, or up to as much as 60days in diabetic patients, as recommendedby the physician; additional drop of the drugshould be administered 30-120 minutes beforethe procedure.As mentioned above, nepafenac is a prodrug [5] ,or a precursor for the formation of the activesubstance, amfenac. Intraocular hydrolases catalyzethe conversion of nepafenac to amfenac — apotent COX-1 and COX-2 inhibitor. Therefore,the condition for making nepafenac active is itspenetration into the ocular structures, which occursfollowing intraconjunctival instillation. Thefirst structure to be reached by nepafenac is thecornea, followed by aqueous humor in the anterior,and then in the posterior chamber. Prodrug’spenetration and transformation into amfenacis fast — peak concentrations of amfenac in theaqueous humor are observed 1 h after instillation.[5] Traditionally, the term “prodrug”, introduced in 1958 by Albert, refers tocompounds that have no biological activity (or low biological activity) andundergo enzymatic or chemical transformations (e.g. hydrolysis) inside the system,producing drugs that exert specific pharmacological actions [24, 25]. The processof secretion/formation of the active substance from the prodrug occurs before,during or after its absorption. In case of some prodrugs, the secretion/formationof the active substance occurs only after the prodrug reaches the planned targetsite. Prodrugs are estimated to account for about 5-7% of all drugs currently usedin medicine. The development of prodrugs has a three objectives: a pharmaceutical,a pharmacokinetic and a pharmacodynamic one. The pharmaceutical objectivepertains to e.g. reduction of problems associated with formulation technology,improvement of solubility or stability; the pharmacokinetic objective focuseson e.g. improvement of absorption, reduction of the metabolism of the drugbefore it reaches the target site(s), increase in the rate of penetration throughbiological barriers or optimization of the duration of the therapeutic effect; thepharmacodynamic objective focuses on e.g. reduction of toxicity, improvementof the therapeutic index or activation of the prodrug into the active compound.In case of Nevanac, the pharmacokinetic and pharmacodynamic aspects are ofhighest importance.42 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 43 – 50Jerzy Z. Nowak: Non-steroidal anti-inflammatory drugs (NSAIDs) in …Compared to the cornea, higher concentrationsof the drug are reached in the ciliary body andthe retina (the rate of conversion of nepafenac toamfenac expressed in pM/min/mg of human tissuewas 0.26 for cornea and 0.39 for the iris/ciliarybody complex; at higher concentrations of the substrate(nepafenac), the respective values were 107and 454, while the value for the retina/uvea complexwas 135 [21]. Applying the drug three times aday guarantees the achievement and maintenanceof amfenac levels that effectively inhibit the COXactivity and prostaglandin production within theocular structures.Many years before ophthalmic nepafenac (Nevanac),amfenac sodium (AHR-5850) was registeredunder the trade name Fenazox in Japan(1986) for systemic use in patients with rheumaticdiseases. Several analogs of amfenac (or2-amino-3-benzoylbenzeneacetic acid) were synthesizedto improve its biological activity profile,i.e. increase the therapeutic index and reduce theadverse effects; these analogs included the amidederivative — 2-amino-3-benzoylbenzeneacetamide(or nepafenac). However, it turned outthat nepafenac’s effect on COX was very weak,but its metabolite formed in the body, amfenac,had a stronger in vivo inhibitory activity againstPGHS, with IC50 values (in µM) against COX-1being 0.25 for amfenac and 64.3 for nepafenac(in parallel studies, the IC50 for diclofenac was0.12 µM); amfenac’s IC50 against COX-2 was 0.15[22]. It should be mentioned that amfenac, withits analgesic effect stronger that that of phenylbutazoneand aspirin in animals, was consideredas a potential oral analgesic at the dose of 100 mgin humans, with rapid onset and many hours’duration of therapeutic action [23].Thus, amfenac (sodium) was the original drug,while nepafenac was developed as an improvedversion — a precursor of amfenac sodium (AHR-5850). In early 1980s, amfenac was tested in detailedtoxicological and comparative studies (withindomethacin, acemethacin, diclofenac and ketoprofen)in rodents, which served as the basis forthe assessment of safety and dosage in humans.Bromfenac2-[2-amino-3-(4-bromobenzoyl)phenyl]acetic acid[C 15H 12BrNO 3; MW 334.16 g/mol] — a derivativeof phenylacetic (arylacetic) acid (Fig. 4).http://military.isl-journals.comFigure 4: Chemical structure of nepafenac, amfenac andbromfenac.As a result of action of tissue hydrolases, nepafenac (with minor effect on cyclooxygenase– COX) is converted to the biologically active amfenac, a strong inhibitor ofCOX-1 and COX-2 activity. It is interesting to note that bromfenac differs from amfenacstructure with the presence of a bromine atom at the 4th position in benzene ring. Likeamfenac, bromfenac is a strong inhibitor of COX activity.The history of bromfenac is short but interesting anddidactic, and therefore deserves being mentioned. Beforethe compound became an active substance in ophthalmicproducts, it was originally an ingredient of oraldrugs. It was available in oral drugs for a short but dramaticperiod. In July 1997, US FDA registered a drugnamed Duract by Wyeth-Ayerst (capsules containing 25mg of bromfenac) for short-term (lasting up to 10 days)treatment of various pain conditions (headaches, muscles,teeth, menstrual pains, post-traumatic pains) andreduction of inflammation symptoms. Due to its stronganalgesic effect, Duract (Bromfenac-Oral), used in theregimen of 1 capsule or 2 capsules taken with mealsevery 6-8 h, with total daily dose not exceeding 150mg — was to offer an alternative to the abused opiate analgesicsin cases of severe pains. Duract grew on popularityand quickly made it to the top of the list of the newpainkillers; according to IMS America, nearly 1.3 millionprescriptions were issued in the US within less thanone year [The Associated Press, Washington, February11, 1998]. Contrary to numerous well-known adverseeffects of opiate treatments, short-term use of Duractwas expected to be safe, and the side effects stated by themanufacturer included only less important symptomssuch as stomach upset as the most common ailment,possible abdominal pains and headaches, nausea andvomiting; less common effects dizziness, somnolenceand blurred vision. In the meantime, US FDA pointedout that jaundice, hepatitis, and even severe hepatic insufficiencyrequiring liver transplant were observed insome Duract (Bromfenac-Oral) recipients, particularlyin patients taking the drug form more than 10 days. Inconsequence, Duract (Bromfenac-Oral) was withdrawnfrom the pharmaceutical market by FDA’s decisiondated 22 June, 1998, due to the risk of severe hepaticcomplications, after only 11 months on the market.43

© Military Pharmacy and Medicine • 2012 • 4 • 44 – 50However, bromfenac was not completely abandoned— after two years of absence, it reappeared in thepharmaceutical market — this time as an ophthalmicdrug: bromfenac ophthalmic solution.Yellox (Croma Pharma/Bausch&Lomb)• • 0,09% ophthalmic drops (0.9 mg ofbromfenac/mL; bottle of 5 mL; active substance— bromfenac sodium as sesquihydrate(C 15 H 11 BrNNaO 3 x 1½ H 2 O). In addition, theproduct contains a preservative — benzalkoniumchloride (0.05 mg/mL = 0.005%), andingredients considered to be inactive, e.g.boricacid, sodium edetate (0.2 mg/mL), emulsifier— polysorbate-80 (1.5 mg/mL), povidone(20 mg/mL). The pH of the solution is 8.3 andthe osmolarity is 300 mOsmol/kg [26, 27].The chemical structure of bromfenac is nearlyidentical to that of amfenac (the active compoundformed of nepafenac), the only difference beinga bromine atom at C-4 carbon, hence the nameof the compound. The presence of bromine hasbeneficial effects on the properties of the molecule:it enhances its lipophilicity and facilitatespenetration through cell membranes of variouseye tissues, contributing to elongation of drug’sinhibitory effect on the activity of COX enzymes,particularly of the COX-2 isoform.Therapeutic indications(accd. to Pharmindex–Okulistyka, 2012):treatment of post-operative inflammation of theeye following cataract removal in adults.Dosage: 1 drop 2x a day, starting on the day afterthe cataract surgery; the drug should be used forthe first two weeks of the post-operative period.The treatment duration should not exceed 2weeks, as there are no safety data availableregarding longer-term treatment.Review articleAccording to Cho et al. [27], bromfenac’s in vitroinhibitory effect on COX-2 was stronger than thatof diclofenac (3.7x), amfenac (6.5x) and ketorolac(18x); however, it must be emphasized that thesevalues were obtained in in vitro studies and donot necessarily reflect the relationships observedin vivo; they are only suggestive of bromfenac’stherapeutic benefits over the listed products.Although Yellox has only recently become availablein Polish pharmaceutical market, it had beenregistered as bromfenac sodium ophthalmic solution0.1% and under the trade name of Bronuck(Senju Pharmaceutical Co., Osaka, Japan) in Japanin May 2000, with the recommendations foruse in the treatment of post-operative inflammation,blepharitis, conjunctivitis and scleritis.Five years later (March 2005), bromfenac wasregistered by the US FDA under the trade nameof Xibrom, in the form of 0.09% solution ofbromfenac sesquihydrate, with the recommendationsfor use in the treatment/prevention ofpost-operative inflammation in patients aftercataract removal. Recommended dosage is 1drop into the affected eye(s), 2x a day 24 h afterthe procedure, continued for 2 weeks. In October2010, US FDA approved a new formula namedBromday, to be used once daily as opposed toXibrom and Yellox, which require a twice-dailyadministration. European registration of Yellox(May 2011) was initiated in 2009 by an applicationsubmitted to EMEA by Austrian companyCroma-Pharma GmbH, which had obtainedthe relevant license from the Japanese companySenju in 2005. Based on the agreement betweenCroma Pharmaceuticals and Bausch&Lomb,both companies distribute the drug in the countriesof the Central and Eastern Europe.Other ophthalmic NSAIDsFollowing instillation onto the eye surface, Yelloxreaches its peak concentration in the aqueoushumor after 2.5-3 h; this concentration is thenmaintained for 12 h.Yellox is a safe medication, with adverse effectsobserved in 2-7% patients including conjunctivalhyperemia, pain, burning, or itching sensationand/or vision disorders, iritis (generally mild andusually transient, principally with no effect on thecourse and the success of the treatment) [26, 27].44 http://military.isl-journals.comActive substances of drugs listed below arephenylalkanoic (propionic) acid derivatives whichare, by their nature,well soluble in water and thuseasier used in ophthalmic products. These includesuprofen, flurbiprofen, ketorolac and pranoprofen.Suprofen(RS)-α-methyl-2-[4-(2-thienylcarbonyl]propionicacid [C 14 H 12 O 3 S; MW 260.31 g/mol] — a derivativeof arylpropionic acid.

© Military Pharmacy and Medicine • 2012 • 4 • 45 – 50Jerzy Z. Nowak: Non-steroidal anti-inflammatory drugs (NSAIDs) in …Before suprofen was marketed as ophthalmic preparation,it had been available at pharmaceutical marketunder the trade name of Suprol (200 mg modifiedrelease tablets/capsules). However, the manufactureand distribution of the drug was discontinued dueto potential toxic effects manifested as acute lumbarpain syndrome and reversible renal insufficiency, mostcommonly manifested as urate nephropathy. Thus, theonly product available at the market is the ophthalmicproduct Profenal.Profenal (Alcon) — 1% Ophthalmic Solution contains10 mg of suprofen per 1 mL and, additionally,thiomerosal (0.005%; 0.05 mg/mL), caffeine (2%;20 mg/mL) and other, less important ingredients.Profenal was approved for medical marketing bythe US FDA in 1987 as a drug to inhibit intraoperativemiosis. According to manufacturer’sinstructions, the drug was to be administered accordingto the following schedule: 2 drops (equivalentto 1 mg of suprofen) into one eye 5x on theday before surgery, and then 3x on the day of theprocedure (the total dose received by the patientduring the two days is ca. 25 times smaller that asingle oral dose of 200 mg).Profenal was available as an ophthalmic productat least until 2007; afterwards, its productionwas discontinued.Flurbiprofen(RS)-α-methyl-2-fluorobiphenyl-4-yl)propionicacid [C 15 H 13 FO 2 ; MW 244.26 g/mol] — a derivativeof arylpropionic acid.Flurbiprofen is present in products with different tradenames, (e.g. Rubifen, Ansaid, Flurwood, Froben) andis used to treat inflammation and pain in the joints.It is also present in popular throat lozenges StrepsilsIntensive. In the available preparations, flurbiprofenis present as a racemic mixture (a mixture of levorotationaland dextrorotational forms: R,S, ±). What’sinteresting, contrary to the levorotational isomer,i.e. S(+)-flurbiprofen, the dextrorotational form, i.e.R(–)-flurbiprofen, has no anti-inflammatory activityand does not inhibit either COX-1, or COX-2. Thedextrorotational isomer, known as tarenflurbir, wasrecently tested under an advanced clinical study programas a potential drug named Flurizan (by MyriadGenetics) to be used in Alzheimer’s disease; however,http://military.isl-journals.comhaving completed phase III studies in nearly 2,000patients, the manufacturer announced suspension offurther registration process. Tarenflurbir is currentlytested in clinical studies in patients with metastaticprostate cancer.Ocufen/Ocuflur (Allergan) are ophthalmic preparationscontaining RS(±)-flurbiprofen at concentrationof 0.03% (0.3 mg/mL); in addition,the product contains 0.005% of thimerosal asa preservative, 1.4% of polyvinyl alcohol (PVA)and a number of less crucial components, usedmostly to stabilize the solution. After being approvedby the US FDA as an agent against intraoperativemiosis, Ocufen (flurbiprofen sodiumophthalmic solution, USP, 0.03%) entered themedical market in the US in January 1987; insome European countries, as well as in India, itis available under the trade name Ocuflur. Ocufluravailable in Belgium is indicated, except forthe indication mentioned above, in the treatmentof inflammation following surgical intervention,laser trabeculoplasty and in preventionof cystoid macular edema after cataract surgery.Comparative clinical studies in patients withpost-operative inflammation following cataractsurgery performed by Diestelhorst et al.[28] showed that the anti-inflammatory effect of0.03% flurbiprofen was weaker than that of 0.1%diclofenac and 1% indomethacin, which led toreduced interest in the drug. Today, flurbiprofen,although still commercially available inmany countries, does not measure up to competitionfrom other, newer products and is a drugthat is relatively rarely used in clinical setting.Ketorolac(RS,+/–)-5-benzoyl-2,3-dihydro-1H-pyrrolysine-1-carboxylic acid [C15H13NO3; MW 255.27g/mol] — a derivative of arylacetic acidKetorolac, present as tromethaminium salt in productswith different trade names (e.g. Toradol, Acular, Minolac),as well as in Sprix Nasal Spray, is an NSAID usedfor short-term treatment of moderate to severe pain.Acular, Acular LS, Acular PF, Acuvail are ophthalmicproducts by Allergan. Acular andAcular LS contain respectively 0.5% and 0.4%solution of ketorolac with tromethamine(NH 2 -C[CH 2 OH] 3 ); in addition, both productsinclude benzalkonium chloride 0.006%45

© Military Pharmacy and Medicine • 2012 • 4 • 46 – 50Review article(0.06 mg/mL) and octoxynol-40 (chemicallyinert detergent, also known as Triton X-100).Acular PF contains a 0,5% solution of ketorolac/tromethamine, without preservatives, i.e. benzalkoniumchloride and octoxynol-40; it isavailable as single use 0.4 mL vials (12 vials perpack). Acuvail (registered by US FDA in July2009 r.) contains a 0.45% solution of ketorolac/tromethamine without preservatives and withthe addition of carboxymethyl cellulose (CMC)which enhances the adhesion of drops to theconjunctiva and cornea [29, 30].Acular (0.5% Ophthalmic Solution) was approvedby the US FDA to be used after cataractsurgeries: 1 drop 4 times per day starting 24h after the procedure for 2 weeks. The officialindications of the drug include also the treatmentof itching that accompanies allergic conjunctivitis.Acular LS is officially registered foruse in reduction of ocular pain and burningafter cataract surgeries, while the newest product,Acuvail, is used in the treatment of painand inflammation after cataract removal. Thedrug may also be used to relieve ocular itchingdue to allergic conjunctivitis (dosage: 1drop — 0.25 mg of the drug 4 times a day) andto treat post-operative inflammation in patientsundergoing surgeries for cataract (1 drop 4times a day starting from the second day afterthe procedure for 2 weeks). According to themanufacturer, the strength of the anti-inflammatoryeffect of ketorolac is comparable to thatof 0.1% diclofenac.Pranoprofenα-methyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid or α-methyl-2-(5H-chromeno[2,3-b]pyridin-7-yl)propanoic acid [C 15 H 13 NO 3 ; MW255,27 g/mol] — a derivative of arylpropionic acid.Pranoprofen (an original product of Yoshitomi Pharmaceuticals,Osaka, Japan) is characterized by a stronganti-inflammatory and analgesic and a weaker antipyreticaction. It was taken by cooperating pharmaceuticalcompanies Yoshitomi and Senju (Osaka) to produceophthalmic drug under the name Niflan.Niflan (Senju, Osaka; the drug known outsideJapan under various names: Oftalar,Pranofen, Pranoflog, Pranox) — 0.1% eyedrops (1 mg pranoprofen/mL). The drug46 http://military.isl-journals.comwas registered in Japan in 1988 and is availableuntil now in some Asian and Europeancountries (Japan, China, Belgium, Italy,Portugal, Spain and Turkey). The drug doesnot possess US FDA registration and is notused in the US. In clinical studies beforeregistration, pranoprofen was shown to produceirritation of conjunctiva, the effect beingeventually eliminated using a combinationof components in future drug formulaof which boric acid appeared to be a crucialcomponent (it is worth of mention that boricacid occurs in formulas of many ophthalmicNSAIDs); other components include:polysorbat-80 and benzalkonium chloride(0.007% = 0.07 mg/mL) and disodium edetate[31].Therapeutic indications for Niflan include inflammationfollowing eye surgery, blepharitis,conjunctivitis and keratitis. Dosage: 1-2 drops 4xduring the day for a period necessary for completeresolution of the symptoms of inflammation.Fenoprofenα-methyl-2-(3-phenoxyphenyl)propionic acid[C 15 H 14 O 3 ; MW 242,27 g/mol] — a derivative ofarylpropionic acid.As mentioned before, fenoprofen ophthalmicdrops were tested in preclinical and clinicalstudies as an ophthalmic anti-inflammatoryand analgesic agent. Eye drops containing 1%solution of fenoprofen as hydrated sodium saltwere tested mostly for prevention of uveitis. Althoughthe efficacy of ophthalmic fenoprofenwas comparable to that of 1% dexamethazonein a rabbit uveitis model [32], the obtained resultswere not very encouraging and the studiesshowed no progress. No positive results werealso obtained in the clinical trials of 1% fenoprofensodium solution in patients with aphakiceyes and chronic cystoid macular edema [33].In consequence, fenoprofen was not introducedas an ophthalmic drug, although its dihydratecalcified form is registered in the US under thetrade name of Nalfon (fenoprofen calcium capsules,USP; 200 mg and 400 mg capsules; PedinolPharmacal, Inc.) for use in e.g. rheumatoidarthritis, osteoarthritis or acute gout episodes.

© Military Pharmacy and Medicine • 2012 • 4 • 47 – 50ConclusionPolish ophthalmologists have currently sixNSAID products at their disposal. Three productscontain diclofenac and, from medical standpoint,are practically identical (although it shouldbe mentioned that one of these products containsno preservative) and can be used interchangeably.One medication contains indomethacin — an activesubstance that has been known in medicalpractice for the longest time. The list is completedby two relatively new fenacs: nepafenac and bromfenac.In the Pharmindex–Okulistyka [Ophthalmology]2012 handbook, the latter two drugscontained in Nevanac and Yellox products areannounced in the part titled New registrations,although, to be exact, both were some time agothe pioneer drugs in the worldwide market ofophthalmic preparations.However, in Poland, Nevanac (nepafenac) andYellox (bromfenac) are new drugs, and thereforemost commonly referred to in current discussions,although the remaining compounds(mainly diclofenac products) are still extensivelyused in worldwide practice.However, let us focus on these two products thatare new to the Polish market. Nevanac containsthe active substance amfenac administered asa precursor compound, nepafenac. Yellox containsthe active substance bromfenac, whichdiffers from amfenac by a bromine atom in thebenzene ring. In other words, bromfenac is abrominated amfenac. The difference may seemsmall, but is a significant one in practical terms.Similarly to other halogens, i.e. fluorine, chlorineor iodine, the non-metal bromine modifiedthe properties of the structure it is boundto — for example, halogenated structures usuallypenetrate cell membranes better. In consequence,bromfenac, when administered intraconjunctivally,would easier/faster penetrateinto the eye than amfenac, which would affectthe concentrations achieved by both compoundsin ocular structures and fluids (cornea,aqueous humor, iris/ciliary body, uvea). Thus,bromfenac would faster reach higher concentrationsat target site (of potential or ongoing inflammation)compared to amfenac. However, itis not amfenac that is the ingredient of the Nevanacdrug — it is nepafenac, which is an amidederivative of amfenac, converted to amfenac inhttp://military.isl-journals.comJerzy Z. Nowak: Non-steroidal anti-inflammatory drugs (NSAIDs) in …ocular tissues by means of ubiquitous hydrolaseenzymes. Nepafenac is, by comparison, a poorPGHS inhibitor (IC 50 = 64 μM against COX-1),but it penetrates into ocular tissues faster thanamfenac; there it is transformed into amfenac,which is a highly active PGHS inhibitor (IC 50 =0.25 μM — COX-1 and 0.15 μM — COX-2) [22].To sum up these considerations, one might saythat the use of a prodrug formula in Nevanacfunctionally balances out the presence of bromineatom in the structure of bromfenac (Yellox). Istherefore the therapeutic efficacy of Yellox (aqueoussolution) and Nevanac (suspension) clinicallycomparable? Theoretically, yes, althoughophthalmologists should remember that everypatient is a non-fully-predictable individual whodoes not have to respond in the same mannereven to very similar drugs. This is due to the factthat drugs contain not only active substances,but also excipients which might have multidirectional,non-specific effects. With regard to thelatter, both Nevanac and Yellox contain benzalkoniumchloride (0.05%) and disodium edetatepreservatives, but differ in all other excipients:Nevanac contains mannitol, carbomer 974P, andtyloxapol, while Yellox contains boric acid, polysorbate80, and povidone. In addition, both compoundshave different pH values: 7.4 vs. 8.3 andslightly different (albeit comparable) osmolarity:305 vs. 300 mOsmol/kg.With reference to the discussion on nepafenacand bromfenac, one should also ask whether thediclofenac products (Dicloabac, Difadol 0.1%,Naclof) are therapeutically different from Yelloxand Nevanac? There is no definitive answer tothis question. In the author’s opinion, the newerfenacs have advantages over the older ones, butthe treatment success is determined by patient’sresponse, both in the terms of therapeutic activityand adverse events. The planned duration oftherapy and frequency of application may alsoprovide a hint when making therapeutic decisions,as both these parameters prefer safer drugs,i.e., in this case, the newer products. However, itmust also be stressed that the therapeutic, i.e.anti-inflammatory and analgesic effects will beachieved with all currently available ophthalmicNSAIDs. Short-term treatments are not as rigorousas long-term ones; the armory of drugs availablefor use over several or a dozen or so days isthus very wide.47

© Military Pharmacy and Medicine • 2012 • 4 • 48 – 50Literature contains comparative data from parallelgroup studies evaluating clinical efficacyof various ophthalmic NSAIDs in various ophthalmicconditions (including prevention andtreatment of postoperative inflammation aftercataract surgery). These included comparisonsof diclofenac 0,1% — flurbiprofen 0.03% — indomethacin1% [28], ketorolac 0.45% — bromfenac0.09% — nepafenac 0.1% [34], as well as other setsof drugs, including glucocorticosteroids, tested inhumans [35-37] and in animal models [38].There are numerous works of this type, however,they were not included in this survey for variousreasons, including clinical picture being blurreddue to the lack of clear differences between drugsor the results originating from small patientgroups which might suggest random character ofthe clinical picture. In order for an analysis of suchfactual material to be reasonable and justified, itshould compare possibly the largest number ofpublished/available studies, including the goals ofthe overall treatment and the treatment with individualdrugs. This, obviously, would be out of thescope of this study.I want to conclude this article with a known opinionshared by the physicians with regard to pharmacologicaltherapy: Oftentimes, therapeuticefficacy of drugs within a particular group is generallysimilar, and the fact, whether a particularReview articledrug is more or less suitable for a particular patient,is determined by the adverse (side) effects ofthat drug. This is also the case for systemic drugs.No patient suffering from inflammatory or painfulconditions of joints, muscles and tendons andchronically receiving NSAIDs would questionthe therapeutic efficacy of drugs containing diclofenacor meloxicam, although when faced withthe risk of adverse effects, e.g. gastrointestinal effects,the latter product may be a more reasonablechoice (though, on the other hand, the range ofavailable diclofenac-based drugs includes newerand safer formulas characterized by modified activesubstance release profiles, biphasic activityand combinations of diclofenac with agents thatprotect gastric mucosa).Now returning to ophthalmic NSAIDs — lookingforward and taking into consideration thedevelopment in the systemic NSAIDs, one mayexpect that completely novel structures withanti-inflammatory and analgesic potential andpotential intraconjunctival application shouldemerge, or that previously-known compoundswould be “revitalized” in the therapeutic sense,enhancing the range of available therapies.AcknowledgementsThe work was funded by the Medical Universityof Łódź (Grant No. 503/1-023-01/503-01).References:Besides the bibliography listed below, informationused in this review is based on registration data forindividual drugs (FDA, EMEA), information providedby manufacturers in product information leaflets andother data published in pharmacological handbooksspecialized in ophthalmic drugs, including Pharmindex– Okulistyka, 2012; Leksykon – Vademecum Okulisty,2011; Leki po Dyplomie — Okulistyka, 2010/2011,and Leki Współczesnej Terapii, 20th Ed., 2010.1. Vane JR: Inhibition of prostaglandin synthesis as amechanism of action of aspirin-like drugs. Nature(New Biology). 1971; 231: 232-5.2. Botting RM: Vane’s discovery of the mechanism ofaction of aspirin changed our understanding of itsclinical pharmacology. Pharmacol Rep.2010; 62: 518-25.3. Ryan A, Godson C: Lipoxins: regulators of resolution.Curr Opin Pharmacol. 2010; 10: 166-72.4. Nowak JZ: [Anti-inflammatory pro-resolvingderivatives of omega-3 and omega-6 polyunsaturatedfatty AIDS]. Post Hig Med Dosw (Online).2010; 64: 115-32.5. Barnes PJ: Glucocorticosteroids: current and futuredirections. Br J Pharmacol. 2011; 163: 29-43.6. Fu JY, Masferrer JL, Seibert K, Raz A, Needleman P:The induction and suppression of prostaglandin H2synthase (cyclooxygenase) in human monocytes. JBiol Chem. 1990; 265:16737-40.7. Kis B, Snipes JA, Busija DW: Acetaminophen and thecyclooxygenase-3 puzzle: sorting out facts, fictions,and uncertainties. J Pharmacol Exp Ther.2005; 315: 1-7.8. Hinz B, Brune K: Paracetamol and cyclooxygenaseinhibition: is there a cause for concern? Ann RheumDis. 2012; 71: 20-5.9. Graham GG, Scott KF: Mechanism of action ofparacetamol. Am J Ther. 2005; 12: 46-55.48 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 49 – 50Jerzy Z. Nowak: Non-steroidal anti-inflammatory drugs (NSAIDs) in …10. Schalanus R: Topical nonsteroidal anti-inflammatorytherapy in ophthalmology. Ophthalmological. 2003;217: 89-98.11. Kim SJ, Flach SJ, Jampol LM: Nonsteroidal antiinflammatorydrugs in ophthalmology. SurvOphthalmol. 2010; 55: 108-33.12. Colin J: The role of NSAIDs in the management ofpostoperative ophthalmic inflammation. Drugs.2007; 67: 1291-308.13. Abelson MB, Sloan J: Nonsteroidal anti-inflammatorydrugs. Current ophthalmic therapy. J Fla Med Assoc.1994; 81: 261-3.14. Hart FD, Boardman PL: Indomethacin: a new nonsteroidanti-inflammatory agent. Br Med J.1963; 2: 965-70.15. Ferreira SH, Moncada S, Vane JR: Indomethacin andaspirin abolish prostaglandin release from the spleen.Nat New Biol. 1971; 231: 237-9.16. Miyake K: Indomethacin in the treatment ofpostoperative cystoid macular edema. SurvOphthalmol. 1984; 28 (Suppl.): 554-68.17. Ahuja M, Dhake AS, Sharma SK, Majumdar DK:Topical ocular delivery of NSAIDs. AAPS J. 2008; 10:229-41.18. Bucolo C, Melilli B, Piazza C, Zurria M, DragoF: Ocular pharmacokinetics profile of differentindomethacin topical formulations. J Ocul PharmacolTher. 2011; 27: 571-6.19. Weber M, Kodjikian L, Kruse FE, Zagorski Z, AllaireCM: Efficacy and safety of indomethacin 0.1% eyedrops compared with ketorolac 0.5% eye drops in themanagement of ocular inflammation after cataractsurgery. Acta Ophthalmol. 2012; doi: 10.1111/j.1755-3768.2012.02520.x.20. Lindstrom R, Kim T: Ocular permeation andinhibition of retinal inflammation: an examinationof data and expert opinion on the clinical utility ofnepafenac. Curr Med Res Opin. 2006; 22: 397-404.21. Ke TL, Graff G, Spellman JM, Yanni JM: Nepafenac,a unique nonsteroidal prodrug with potentialutility in the treatment of trauma-induced ocularinflammation: II. In vitro bioactivation andpermeation of external ocular barriers. Inflammation.2000; 24: 371-84.22. Gamache DA, Graff G, Brady MT, Spellman JM,Yanni JM: Nepafenac, a unique nonsteroidal prodrugwith potential utility in the treatment of traumainducedocular inflammation: I. Assessement of antiinflammatoryefficacy. Inflammation.2000; 24: 357-70.23. Jain AK, Hunley CC, Kuebel J, McMahon FG, RyanJJ: Analgesic efficacy of amfenac, aspirin and placeboafter extraction of impacted teeth. Pharmacotherapy.1986; 6: 236-40.24. Rautio J, Laine K, Gynther M, Savolainen J: Prodrugapproaches for CNS delivery. The AAPS J.2008; 10: 92-102.25. Olejniczak AB, Zawilska JB: [Future therapies –prodrugs]. Farm Pol. 2012; 68: 350-7.26. Jones J, Francis P: Ophthalmic utility of topicalbromfenac, a twice-daily nonsteroidal antiinflammatoryagent. Expert Opin Pharmacother.2009; 10: 2379-85.27. Cho H, Wolf KJ, Wolf EJ: Management of ocularinflammation and pain following cataract surgery:focus on bromfenac ophthalmic solution. ClinOphthalmol. 2009; 3: 199-210.28. Diestelhorsta M, Schidl B, Konen W, Mester U, RajPS: Efficacy and tolerance of diclofenac sodium0.1%, flurbiprofen 0.03%, and indomethacin 1.0% Incontrolling postoperative inflammation. J CataractRefract Surg. 1996; 22 Suppl 1: 788-93.29. McCormack PL: Ketorolac 0.45% ophthalmic solution.Drugs Aging. 2011; 28: 583-9.30. Yilmaz T, Cordero-Coma M, Gallagher MJ: Ketorolactherapy for the prevention of acute pseudophakiccystoid macular edema: a systematic review. Eye(Lond). 2012; 26: 252-8.31. United States Patent Number 4,607,038 – OphthalmicPranoprofen Compositions (Ogata K, Yamamoto Y,Ozaki Y): Date of Patent: 1986 Aug 19.32. Harris LS, Kahanowicz Y, Hughes J: Ocular antiinflammatoryeffects of fenoprofen. Arch Ophthalmol.1974; 92: 506-8.33. Burnett J, Tessler H, Isenberg S, Tso MO: Doublemaskedtrial of fenoprofen sodium: treatment ofchronic aphakic cystoid macular edema. OphthalmicSurg. 1983; 14: 150-2.34. Bucci FA, Waterbury LD: Prostaglandin E2 inhibitionof ketorolac 0.45%, bromfenac 0.09%, and nepafenac0.1% in patients undergoing phacoemusification. AdvTher. 2011; 28: 1089-95.35. Sivaprasad S, Bunce C, Crosby-Nwaobi R: Nonsteroidalanti-inflammatory agents for treating cystoidmacular oedema following cataract surgery. TheCochrane Library 2012, Issue 2.36. Brennan KM, Brown RM, Roberts CW: A comparisonof topical non-steroidal anti-inflammatory drugs tosteroids for control of post cataract inflammation.Insight. 1993; 18: 8-9.37. Roberts CW, Brennan KM: A comparison of topicaldiclofenac with prednisolone for postcataractinflammation. Arch Ophthalmol. 1995; 113: 725-7.38. Stroobants A, Fabre K, Maudgal PC: Effect of nonsteroidalanti-inflammatory drugs (NSAID) onthe rabbit corneal epithelium studied by scanningelectron microscopy. Bull Soc belge Ophthalmol.2000; 276: 73-81.Additional reference:39. Nowak JZ, Dzielska-Olczak M: [New NSAIDs andmodern forms of anti-inflammatory drugs]. PulsMedycyny. 2012 (educational issue).http://military.isl-journals.com49

© Military Pharmacy and Medicine • 2012 • 4 • 51 – 56Dorota Kołodziej, Radosław Ziemba: The role of paramedics in British emergency …The role of paramedics in British emergency aid systemDorota Kołodziej, Radosław ZiembaMilitary Centre for Pharmacy and Medical Technology in Celestynow, PolandEmergency MedicineAuthor’s address:Radosław Ziemba, Military Centre of Pharmacy and Medical Technique, ul. Wojska Polskiego 57,05–430 Celestynów, Poland; e–mail: zx11@op.plReceived: 2012.09.21 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:The article presents the role of paramedics in the United Kingdom’s emergency aid system, includingdifferences in the British programs of training of technicians and paramedics with particular focus onparamedic qualification degrees. In addition, the article presents the United Kingdom’s pre-hospitalcare system in cases of serious disorders and injuriesKey words: emergency calls, technician, paramedic, training programs, United Kingdom paramedicqualification degrees, pre-hospital care.Paramedics in the UnitedKingdom’s emergency aid systemThe Emergency Medical Service (EMS) is a standaloneorganizational unit of the United Kingdom’semergency aid system. First aid providedby two-person field teams consisting of medicaltechnicians and paramedics. The team is highlytrained in emergency aid and authorized to:— — administer certain drugs, assess and monitorvital parameters, including heart rate and function,respiratory rate;——use specialist medical equipment, such assemiautomatic external defibrillators (SAEDs).The scope of activities of the Emergency MedicalService includes;1) departures to emergency cases;2) transportation of patients with medicalindications to hospitals;3) emergency transportation of patientsbetween hospitals;4) Transportation of disabled individualsrequiring specialist or nursing care.http://military.isl-journals.comThe following are considered emergency cases:1) accidents;2) poisonings;3) gastrointestinal bleeding;4) risk of abortion, deliveries;5) suspected insufficiency of coronary arteriesand circulatory insufficiency.Emergency calls include transportation ordersplaced by physicians and midwives regardingtransportation of patients between hospitals.Sanitary transportation is considered an integralpart of the healthcare system. Transportation ofpatients for diagnostic or treatment proceduresthat do not require hospitalization, as well astransportation of physicians to home visits is carriedout in a non-emergency setting.The organizational development of the EMS isaimed at:1) providing medical care of multi-site andmulti-organ injuries;51

© Military Pharmacy and Medicine • 2012 • 4 • 52 – 562) shortening the time to reach the injuredpatients;3) establishing specialist centers for the treatmentof such injuries. Following the deliveryof patients with multi-organ injuries to thenearest hospital, the care of these patientsis taken over by emergency care units inhospital emergency wards. These are multidisciplinaryteams of physicians, nursesand paramedics, who perform a wide-scalediagnostics of the patient. According to theBritish physicians, this allows to provideaid in a timely manner and avoids potentialomission of any procedural stage, thusleading to fast initiation of causal treatment.Paramedics are independent individuals workingby themselves or in groups with patients ofall ages, depending of their professional competence.They are the main members of interdisciplinaryteams who belong to different organizations.Successful performance of one’s duties asa paramedic requires identification and understandingof social and economical conditions ofpatients. This helps in planning, providing andimproving medical care.Paramedics’ duties are classified according to afive-grade system including the following grades:——Emergency Medical Technician (EMT);——Paramedic;——Paramedic Practitioner (incl. EmergencyMedicine Practitioner);——Advanced Paramedic Practitioner;——Consultant Paramedic.The term “paramedic” and its meaning are subjectto legal protection. Career development is a lifelongconcept. In-service training creates basis forthe development of college-level training methods.Paramedics are capable of acting upon first contactwith the patient without seeking help fromother healthcare professionals. They are alsoresponsible for the quality of care they provide topatients by adhering to principles and applyingmedical knowledge in their practice.Paramedics of all grades should:1) have the knowledge and understanding ofchanges occurring in the human body fromneonatal to elderly age;Review article2) be capable of delivering aid to individualsand groups in a wide variety of situations,including aid in acute, primary and criticalcare conditions presenting complex andvariable problems as resulting from multipathologydisorders and injuries;3) be capable to combine theoretical knowledgewith practical skills and to develop problemsolving schemes;4) be able of critical self-assessment anddrawing appropriate conclusions;5) be able to apply clinical examinations andcase studies in their paramedical practicein order to provide patients with optimumcare;6) be able to work in teams and cooperate withother professionals;7) be able to understand patient’s autonomy,internal reservations and rights as well as beable of providing support to patients;8) be capable of referring the patient to a centerof appropriate reference level in case thepatient’s needs are beyond the paramedic’scapabilities.Differences in the training programsof technicians and paramedicsin the United KingdomThe requirement for the training of techniciansand paramedics are different. Part of the trainingis provided in ambulances and part is providedin hospitals; the training also includes a masterdegreeprogram.The candidates go through an intensive initialtraining of about 12 weeks, including classes onanatomy, physiology, intensive care and ambulancedriving. The theoretical part of the trainingis prepared by the Institute of Health Care Development(IHCD).The clinical care is provided by technicians andparamedics in line with national clinical protocols(procedural standards). These are translatedinto local protocols which may be approved bylocal committees of hospital consultants, familypractitioners, pharmacists, senior emergencyservice managers supervised by medical emergencyexecutives. The list of skills and the list ofdrugs that can be administered by technicians isprovided in schedule A.52 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 53 – 56Dorota Kołodziej, Radosław Ziemba: The role of paramedics in British emergency …After the basic training and after passing theoreticaland practical exams, technicians work forone year under supervision of an experiences,trained technician or paramedic. At some centers,technicians keep books to record their practicalskills. After a one-year training, techniciansreceive licenses for independent practice; however,they should take part in subsequent trainingsevery 3 years.Technicians striving to obtain the paramedicdegree must have at least 12 months of professionalexperience as qualified technicians andmust be selected by their employing institution.Today, paramedics in the United Kingdom aresubjected to an at least two-month long, intensivetraining in:1) anatomy;2) physiology;3) trauma surgery;4) procedures to follow in emergency cases:including:a) pregnancy,b) pediatrics,c) psychiatry.In addition, paramedics undergo practical trainingin emergency wards, operating rooms andinvasive cardiology labs. During the training,paramedics have to••perform at least: 25 intravenous punctures••25 intubations••interpretations of ECG records. Next, theyundergo training in:——Advanced Life Support (ALS);——Advanced Cardiac Life Support (ACLS);——Advanced Trauma Life Support (ATLS);——different medical scenarios in adults and children.These are preceded by practical trainingand serve as a basis.to apply for a paramedic certificate.Degrees of paramedic qualificationsin the United KingdomAmbulance Clinician/Technician;Student ParamedicAmbulance clinicians/technicians and studentparamedics should have completed high schooleducation and knowledge of the basic concepts ofpatient care. In addition, they must complete thehttp://military.isl-journals.combasic training program organized by the employinginstitution in cooperation with High EducationInstitution (HEI) partners.At this level, the staff is capable of issuing accurateinitial diagnosis and plan further actions.Thanks to their knowledge and skills, the paramedicsare capable of differentiating betweenlife-threatening and non-life-threatening conditions,interpret and record basic observations andpatient’s personal, family and social history whileproviding aid to the patient. Using the informationobtained from the patient, paramedics formulateconclusions regarding the nature of thedisorder or injury and take actions to manage thepatient and stabilize their conditions accordingto clinical guidelines. The scope of paramedics’activities includes protection of respiratory tract,defibrillation and pharmacotherapy.In more complex cases requiring higher skills,paramedics should seek advice from more experiencedcolleagues.At this stage of the training, high school graduatesshould focus on gaining their own experienceand ability to draw conclusions so as to beable to face the upcoming challenges. In addition,they should be well-coordinated and efficientwhile providing aid to the patients.The paramedics have to be able to work in teamsand establish contacts with specialists in differentareas. Thanks to the professional supervision,own reflections and discussions on everyencountered case, the paramedics systematicallyimprove their professional skills and as part ofthe life-long competence — improving process.Registered paramedicThe registered paramedic must have the knowledge,understanding and capability of practicalapplication of the principles or paramedic serviceas developed in cooperation with the HighEducation Institution (HEI), and taught to themwhile studying at that institution.They should be ready for unassisted work asa team member. At this grade, a paramedic iscapable of using their knowledge in unassistedwork aimed at providing patients with best aidpossible. This includes advanced airway patencyprotection procedures, intravenous fluid therapy53

© Military Pharmacy and Medicine • 2012 • 4 • 54 – 56and pharmacotherapy using medicines availableto registered paramedics, as well as other invasiveprocedures. Paramedics must also be able toforesee the future development of patient’s conditionand decide on the appropriate referral hospitaldepending on needs.They should be proficient, co-ordinated andconfident of their skills while delivering care topatients. It is important that a paramedic is capableto make an unassisted assessment of patient’scondition and, based on own experience, to makea decision that would be best for the patients’needs. If needed, they should be able to explainthe measures taken, step by step.Through studying and clinical practice theyshould be able not only to improve their skills,but also to evaluate their personal strengths.They should also be able to embrace the role of asupervisor and mentor of others,Paramedic assistantA paramedic assistant should have bachelor’sdegree education compliant with the curriculumdeveloped by the employing institution in collaborationwith the HEI. This professional graderequires level 6 academic education.Education at this level is associated with proficiency,co-ordination and confidence in deliveringcare. While observing appropriate proceduralstandards, paramedic assistants should beable to work alone or as team leaders.Paramedic assistant’s duties include physicalexamination and collection of the medical historyof a patient. Being up-to-date with the resultsof scientific studies and capable of appropriatelyassessing clinical condition, paramedic assistantsmay provide advice regarding health promotion,prophylactics and prevention of injuries.Thus-trained paramedics are prepared for unassistedpreparation of healthcare programs. Theymay also act as mentors and supervisors ofyounger colleagues, as well as to provide trainings.Advanced Paramedic PractitionerThe grade of Advanced Paramedic Practitionerrequires a grade 6-7 academic education compliantReview articlewith the curriculum developed by the employinginstitution in collaboration with the HEI.Candidates are required to have obtained a master’sdegree.A paramedic with such background will providecomplete clinical safety to victims while workingalone or as a team leader.Advanced practitioners should be able to examineand manage patients in acute and chronicand to complete patients’ full medical, social andfamily history.With their knowledge and skills they should beable to develop care plans that might make itunnecessary for the patient to be hospitalized ifthere is no specific need.Advanced practitioner should be up-to-date withthe results of recent scientific studies and capableof appropriately assessing patient’s clinical image.They may provide advice regarding health promotion,prophylactics and prevention of injuries.Thus-trained paramedics are prepared for unassistedpreparation of healthcare programs. Theymay also prescribe drugs not available to grade 2/grade 3 paramedics. Thanks to their knowledgeand experience, they may also act as mentors andlecturersConsultant ParamedicConsultant paramedics are organizational leaders.They must be professionally registered paramedicsand have a minimum of 10 years of professionalexperience as paramedics.The consultant paramedics embrace four areas:1) Clinical practice experts – working at theforefront of their fields, leading clinicalexaminations and planning individual elementsof examinations both by themselvesand in teams. They work with professionalorganizations with the aim to developguidelines to higher-grade paramedics. Inaddition, they develop clinical trials in collaborationwith academic centers.2) They are involved in research and otheractivities to support training, propose tasksto involve wider circles of medical professionalsand carry out audits at all levels.54 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 55 – 563) By combining education with training (e.g.by holding meetings), they promote evidencebased clinical information across the wholerange of clinical services and encourageprofessional culture.4) They are professional leaders capableof incorporating conclusions regardingpatients’ condition with national healthcaresystem guidelines and collaborationwith various organizations, includingDepartment of Health, Health PromotionCouncil, Quality Assessment Agency or theCommission for Health.Consultant Paramedics may specialize in anybranch of clinical care, in particular in:——emergency pre-hospital and hospital care——(including emergency medicine);——critical and unscheduled medical care;——ground and air rescue operations, typically——provided by ambulance personnel.In either branch, paramedic consultants shouldbe involved in the development of standards forthe functioning of rescue services.The initial concept of emergency servicesincluded prompt response to emergencies, deliveryof first medical aid and transportation ofpatients to hospitals.Dorota Kołodziej, Radosław Ziemba: The role of paramedics in British emergency …Pre-hospital care in serious ailmentsand injuries in the UKPatients with serious ailments or injuries areconsidered a priori as requiring transportation tohospital (for further treatment).Ambulance care is available at telephone numbers999 or 112.After determination of the accident location,ambulances are notified by short wave radio ormobile phones from the Emergency NotificationCentre (ENC). Many ambulances are equippedwith geolocation systems allowing the dispatchersto identify units (mostly ground units) closestto the accident site.Digital terminals are also used to record regularambulance tasks, such as times of departure toand return from the accident site or the hospital,thus reducing the load on the radio band, whichis required for transmission of other data.The calls are classified into three categories:——“A” — if the condition may be life-threatening;——“B” — if the condition is serious, but not immediatelylife-threatening;——“C” — if the condition is neither serious, norlife-threatening.Over recent 25 years, this role has changed dramaticallyand now includes pre-hospital care,oftentimes requiring advanced clinical skills.Current requirements oblige paramedics toconstantly improve their skills which elevatesrequired educational level to academic levels.The clinical rescue personnel may be dividedinto medical care assistants, technicians andparamedics. Most ambulance personnel starttheir work as assistants, later on being trainedto be technicians. After another twelve monthsof practice they may start training to acquire theparamedic degree.After this training, they may be registered asparamedics.The existing training curriculum is verified viaEdexcel. The system encompasses data frompractical training and academic-level education.http://military.isl-journals.comThe category is determined by the Advanced MedicalPriority Determination System (AMPDS)used by the dispatchers to receive alarm calls.The British government has defined standards forambulance services. According to these standards:1) 75% of category A calls should be receivedand provided for within 8 minutes afterdetermination of accident site;2) 95% of category B and C calls should be providedfor within 14 minutes in urban areasand 19 minutes in non-urban areas (urbanareas are defined as areas with populationdensity of more than 2.5 person/acre).The personnel of call-receiving ambulances consistsusually of paramedics and technicians. Thedecision to mobilize a particular team is mateby senior dispatcher who has to have skills butdoes not have to have experience in deliveringfirst pre-hospital care (this role is not performedby physicians).55

© Military Pharmacy and Medicine • 2012 • 4 • 56 – 56Besides mobilization of an appropriately equippedand manned ambulance, it is possible to mobilizea single paramedic riding a motorcycle or drivinga car, particularly in urban agglomerations or incases of remote locations.Both in case of category A, as in case of categoryB/C calls, the response to the call may be providedby immediate response vehicle manned by paramedicsor emergency care technicians equippedwith devices to provide the patient at the accidentsite, or by a first aid unit comparable to ambulance.Aid may be provided by a physician, fire brigadepersonnel or the police. If the patient is providedfor within 8 minutes by non-medical personneland a fully manned and equipped personnelshould arrive within 14-19 minutes (dependingon the area), the dispatcher may decide that theambulance arrival is redundant.Many emergency services are supported by dispatcherspresent at sites of more complex events,e.g. accidents on major roads.In order to reduce the time required to respondto a call, special software is used to plan anddeploy teams (motorway junctions, railroad stations)at sites with large numbers of calls. Thisoffers better chances to patients in densely populatedareas.Review articleVolunteer first aid units are used to provideprompt arrival of caregivers to victims in somesuburban areas.They are comprised of personnel not employedin emergency care, but trained by the ambulancepersonnel and equipped with additionalgear (oxygen, airway clearing devices, automaticexternal defibrillators (AEDs)).If available, Air Ambulance units are also used torescue the victims. Currently, there are 12 suchunits in the UK. All units except for LondonAir Ambulance are manned with paramedicsor technicians.The London Air Ambulance teams always includea physician (completing their specialization orhaving 2nd degree specialization in anesthesiologyand intensive care), who had completed anintensive training in accident site managementand pre-hospital care.The Air Ambulance takes part in rescuing victimswith extensive injuries and provides immediatetransportation to hospital following resuscitationprocedures typical for resuscitation rooms performedat accident sites. The dispatcher may alsomobilize a volunteer physician from the ImmediateMedical Care system.References:1. Black John J. M., Davies Gareth D.: “Resuscitation”,“International EMS Systems: United Kingdom”,2005, no. 64, p. 21-29.2. British Paramedic Association College of Paramedics:A Curriculum Framework for Ambulance Education,February 2006, Official Website of BPO.3. Jakubaszko J.: „Założenia organizacyjne systemumedycyny ratunkowej”, – artykuł” Proceduryorganizacyjno – ratownicze i lecznicze w nagłychstanach zagrożenia życia”, POZKAL,Inowrocław 1996 , s.11-17.4. Koronkiewicz A., Murakowski M., Nowacki W.:„Systemy organizacji i finansowania pomocy doraźneji transportu sanitarnego w wybranych krajach Europyna tle sytuacji w Polsce”, Centrum Organizacji iOchrony Zdrowia, Warszawa 1994.5. Zawadzki A.: „Medycyna ratunkowa i katastrof:,PZWL, Warszawa 2006.6. Doraźna pomoc lekarska, pod red.: Kamiński B.,Dziak A. PZWL Warszawa 1988.56 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 57 – 60Jerzy Bertrandt at al.: Energy expenditure as the basis for determination …PhysiologyEnergy expenditure as the basis for determinationof nutritional demand in soldiersJerzy Bertrandt 1 , Anna Kłos 1 , Bartosz Bertrandt 21Department of Hygiene and Physiology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland.2Military Research and Deployment Center for Food Services, Warsaw, Poland.Author’s address:Jerzy Bertrandt, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland;phone: (+48) 22 685 31 34, 601 853 117, e–mail: J.Bertrandt@wihe.waw.pl.Received: 2012.10.29 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:The study summarizes the history of studies to determine the nutritional demand in soldiers of differentarmies, both in Poland and worldwide. Standard energy values of food rations as used for planning andproviding nutrition to soldiers over the last century were presented.Key words: energy expenditure, food rations, military service .IntroductionGood nutrition is one of the fundamental factorsallowing soldiers to maintain high physicalfitness and good mental condition. Such conditionsmay only be achieved by proper nutritionthat covers all nutritional demands of the body.The main principle of rational nutrition is that thefood should deliver appropriate amount of energyto match the energy expenditure. In nutrition,the energy expenditure values are the measureof calorific demand of human body that may becovered only by the food intake. Thus, the knowledgeof daily energy loss is the basis for determinationof energy values of nutritional standardsfor populations homogenous in terms of gender,age, body weight and height, performing similarworks and living in similar conditions.The question of daily energy expenditure, energyvalue of food and, in consequence, the energybalance, are of particular importance in thehttp://military.isl-journals.comarmy. Knowledge of the physical burden associatedwith soldiers’ training, type of military unitand the specificity of service should be an essentialelement in nutrition planning which has tocover the energy demand and provide the bodywith all required nutrients in appropriate quantitiesand ratios.History of the studies ofenergy demand in soldiersHistory of determination of nutritional demandsand in particular the energy demand in soldiersdates back to the 19th century. Soldiers’ nutritionwas usually the subject of interest for militaryhealthcare services, as it directly affected thesoldier’s health and the efficacy of their action.Hence, in 1863, responsibility for nutrition in theUS Army was bestowed by law to the militaryhealthcare service [1]. The regulations were verifiedin 1877 and have remained in force ever since,including appropriate amendments. According57

© Military Pharmacy and Medicine • 2012 • 4 • 58 – 60to these regulations, Medical Corps officers arealso responsible for soldiers’ nutrition:“The officers of the Medical Department of theArmy shall unite with the officers of the line(under such rules and regulations as shall be prescribedby the Secretary of War) in superintendingthe cooking done by the enlisted men; and theSurgeon General shall promulgate to the officersof said Corps such regulations and instructionsas may tend to insure the proper preparation ofthe ration of the soldier.” [2]About 1870, first studies were conducted inEurope to measure the physiological load of soldiersburdened by the accouterment of differentweight, training at different ambient temperatures.These and subsequent studies conductedin Europe and the US led to determination ofenergy expenditure of humans undertakingvarious forms of physical activity, e.g. marching,including the carried load. The above studies,albeit encumbered with large margin oferror, showed that soldiers may be burdened withenergy expenditure in the range of 5,000-6,000kilocalories per day, depending on the accoutermentweight and outside temperature [3]. However,determination of energetic and nutritionalneeds of soldiers was at that time based mainlyon the average consumption of food. The foodration proposed at the end of World War I by theQuartermaster General of the US Army MedicalCorps was based on the results of the studies onthe quantities of standardized food consumed bythe soldiers in 400 canteens in years 1917-1918.The results of the studies allowed to determinethe mean energy value of food consumed at thelevel of 3,633 kcal with the actual values fallingwithin the range of 3000 to 4000 kcal [4,5]. Subsequentstudy of the energy demand in soldiers,based on calculations of the energy values of foodrations were conducted in the US in 1941. Thestudy covered a total of several hundred unitsof infantry, air force, armored troops, artillery,engineering troops, chemical troops, cavalry,quartermaster troops, logistic services troops,medical troops, military training centers andothers. The mean daily energy value of food consumedby soldiers was 3,694, ranging from 3,132to 4,135 kcal. The highest energy value was measuredfor food rations dispensed in autumn season(September-November — 3,960 kcal), whileReview articlethe lowest energy value was measured for rationsdispensed in spring season (March-May — 3,570kcal) [6,7,8,].The results did not differ significantly fromthese obtained in years 1917-1918. A study conductedin 1943 in 99 canteens of the US Armyground forces and encompassing 130,000 foodrations showed that the mean energy value of adaily ration was 3,468 kcal, ranging from 2,774to 4,644 kcal [9]. Finally, a study to determinethe energy demand in all US Army troops wasundertaken and completed in the spring of 1945[10]. The mean energy value of the food rationsconsumed by soldiers was 3,744 kcal and rangedfrom 3,471 to 4,078 kcal. The mean energy valuedetermined in the study was very similar to thevalues obtained for food rations in the studiesconducted during both World war I (3,633 kcal),and World War II (3,694 kcal).During the World War II, the energy value offood rations in the British Army was higher thanthat in the American food rations and amountedto 5,127 kcal in January 1942. Due to the overlyhigh weight of the rations, the energy value wasreduced to 4,562 kcal in May 1942 [11].Results of subsequent studies served as basis forrevisions of nutritional standards for the Americansociety; changes in the nutritional recommendationsfor soldiers followed these revisions.Studies of the energy expenditureof soldiers in PolandAlso in Poland, studies of energy expenditure ofsoldiers in active service were conducted as earlyas before World War II [12,13].The nutritional tables for Polish soldiers, developedin early 1920s, determined the minimumnutritional demand of soldiers. However, theenergy and nutritional value of rations actuallyused was insufficient, leading to hunger amongsoldiers. Therefore, the nutritional standard wasrevised and the energy value was established at2,900 kcal and later at 3,800 kcal [14].The history of studies of the energy expenditureof soldiers of the Polish Army dates back to 1925,when major dr. Gustaw Szulc determined theenergy load of soldiers in military service.58 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 59 – 60Jerzy Bertrandt at al.: Energy expenditure as the basis for determination …Table 1: Changes in the nutrition standards in the US Army (1943–1985) [15].NormativedocumentStandard*Energy †(kcal)Protein(g)Fat(%kcal)Calcium(mg)Iron(mg)Vit. A(IU)Thiamin(mg)Riboflavin(mg) Niacin(mg)Vit. C(mg)FNB RDA‡ 1943 3.000 70 — 800 12 5.000 1.8 2.7 18 751945 3.000 70 — 800 12 5.000 1.5 2.0 15 75AR 40-250§ 1947 3.600 100 — 700 — 5.000 1.6 2.2 16 501949 3.600 100 — 700 — 5.000 1.6 2.2 16 503.000# 100 — 700 — 5.000 1.6 2.2 16 50Tri-ServiceRegulation **1968 3.400 100

© Military Pharmacy and Medicine • 2012 • 4 • 61 – 66Jerzy Bertrandt at al.: Sodium and potassium content of daily food rations …PhysiologySodium and potassium content of daily food rations of studentsof the Main School of Fire Service in WarsawAnna Kłos 1 , Maryla Długaszek 2 , Jerzy Bertrandt 1 , Wiesława Szymańska 31Department of Hygiene and Physiology, Military Institute of Hygiene and Epidemiology, Warsaw, Poland.2Institute of Optoelectronics, Military Institute of Technology, Warsaw, Poland.3Department of Health, Ministry of Interior, Warsaw, Poland.Author’s address:Jerzy Bertrandt, Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland;phone: (+48) 22 685 31 34, 601 853 117, e–mail: J.Bertrandt@wihe.waw.pl.Received: 2012.11.10 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Introduction:Besides carbon, hydrogen, nitrogen and oxygen, human body contains about 60 other elements,most of which are classified as minerals. They account for ca. 3% of body weight in neonatesand about 4% of body weight in adults. Since human body is unable to synthesize minerals, they haveto be supplied with food in appropriate amounts and ratios. Among macroelements, i.e. elements withhuman body content of more than 0.01% and safe or recommended intake of more than 100 mg, sodium(Na) and potassium (K) play a particular physiological role.Material and methods: The goal of the study was to assess the content of potassium and sodium in dailyfood rations (DFRs) dispensed for consumption and actually consumed by the students of the MainSchool of Fire Service (MSFS) in Warsaw. The study material consisted of daily food rations dispensedfor consumption to MSFS students. Sodium and potassium content in analyzed samples was determinedby atomic absorption spectrometry (AAS).Results: Mean sodium content of the analyzed DFRs was 7,039.4 ± 1,097.6 mg, compared to 6,271.1 ± 996.2mg in actually consumed meals. Mean potassium content of the analyzed DFRs was 3,477.7 ± 637.2 mgActually consumed rations included 3,099.1 ± 550.6 mg of potassium. Sodium and potassium supplywas different in individual months of the study.Conclusions: The sodium content of daily food rations both dispensed for consumption and actuallyconsumed was several times higher than the recommended standards. The potassium content of dailyfood rations was lower than the standard value. Rations dispensed for consumption covered 99.4%,while rations actually consumed covered 88.9% of the standard demand. Attempts should be made toreduce the sodium intake by raising consumers' awareness of the detrimental health effects of excess saltand by appropriately selecting the products included in the diet.Key words: sodium, potassium, food ration.IntroductionCivilization brings many threats to the quality ofhuman nutrition and contributes to the developmentof bad nutritional habits in the population.http://military.isl-journals.comAccording to the World Health Organization,inappropriate nutrition at young age significantlyimpacts the development of numerouschronic non-infectious diseases at adult age. This61

© Military Pharmacy and Medicine • 2012 • 4 • 62 – 66pertains to cardiovascular and gastrointestinaldiseases, as well as to some cancers [1].Minerals are not synthesized in human bodyThey must be delivered to the body with foodand drinks in appropriate quantities and ratios.In special cases, they may be supplied as dietarysupplements to the food rations. Minerals playdual role in human body: they are either buildingmaterials (calcium, phosphorus, iron) or theyregulate the biochemical processes in the body(potassium, sodium, magnesium, copper, zinc)[2]. Many authors observed too low supply ofcalcium, magnesium and iron accompanied byexcess amounts of sodium and phosphorus indaily food rations of students [3,4].In the context of the important role of minerals inthe maintenance of good health, as well as prevalentabnormalities consisting in their too-low (calcium,magnesium, potassium, iron) or too-high(sodium, phosphorus) intake, appropriate supplyof these elements in food rations is reasonable.As shown by the studies of the nutritional habitsof Poles, these habits are far from current recommendations,also with regard to the supply ofappropriate standard amounts of minerals [5].Sodium and potassium are elements found inmany food products. Salt, i.e. sodium chloride, iswidely used to enhance the taste of food products;in addition, being a good preservative, itis widely used in food processing. The intake ofsodium is an important element of public health,as reduction of this intake allows to reduce themean arterial pressure in the population.Potassium, originating mostly from fruits andvegetables, plays many physiological roles and isinvolved in similar processes as sodium. Therefore,the sodium-potassium balance is essentialfor normal functioning of the system.The goal of the study was to assess the content ofpotassium and sodium in daily food rations dispensedfor consumption and actually consumedby the students of the Main School of Fire Servicein Warsaw.Material and methodsThe study was conducted between Novemberand July during the academic year 2011/2012.Original articleThe study material consisted of daily food rationsdispensed for consumption to MSFS students.Sodium and potassium content was determinedin DFRs dispensed for consumption and in plateleftovers. Actual intake of sodium and potassiumwas the difference between the content of theseelements in DFRs dispensed for consumptionand the content of these elements in the leftovers,Daily food rations collected for analysis wereweighed, shred and homogenized. The sampleswere collected from the homogenate [6]. Sodiumand potassium content in analyzed samples wasdetermined by atomic absorption spectrometry(AAS) using a GBC AVANTA Σ apparatus. Thesodium content was determined by flame techniqueat λ = 330.2 nm. The accuracy of the analysisof certified standard was 94.2%. Potassiumwas determined at λ = 766.5 nm. The accuracy ofthe analysis of certified standard was 99.4%. CsClwas used as the deionizing buffer in concentrationof 2000 μg/mL [7]. The obtained results weresubjected to statistical analysis [8].ResultsThe mean energy value of the tested dailyfood rations dispensed for consumption was3,211.2 ± 362.5 kcal. The protein content in theDFRs was 107.7 ± 18.5 g accounting for 13.4%of total ration energy. The fat in the amountof 103.6 ± 22.1 g accounted for 29%, and carbohydratesin the amount of 462.0 ± 362.6 gaccounted for 57.6% of the energy value in thedaily food rations. The energy value of actuallyconsumed daily food rations, i.e. rations dispensedfor consumption minus the plate leftoverswas 2,944.8 ± 338.5 kcal. Protein, fat andcarbohydrates accounted respectively for 13.3%,27.7% and 59% of total energy value.Mean sodium content in the analyzed DFRs dispensedfor consumption was 7,039.4 ± 1,097.6 mgThe sodium content of the leftovers accountedfor 10.9% of total sodium content; thus, theactually consumed daily food ration contained6,271.1 ± 996.2 mg of sodium. (Table 1).Mean potassium content in DFR dispensed forconsumption was 3,477.7 ± 637,2 mg, rangingfrom 2,441.7 mg to 4,773.1 mg. Similarly as in thecase of sodium, potassium content of plate leftoversaccounted for 10.9% of total potassium contentin the dispensed DFR. Therefore, the actually62 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 63 – 66Jerzy Bertrandt at al.: Sodium and potassium content of daily food rations …consumed rations delivered 3,099.1 ± 550.6 mgof potassium.Variability in the sodium and potassium supplywas observed in the dispensed DFRs in individualmonths (Table 2).Considering the seasonal changes in the supplyof elements, the lowest and the highest sodiumcontent in the consumed DFRs was observedTable 1: Mean sodium and potassium content of the dailyfood rations of the MSFS students, in mg.Element(mg)Sodium(Na)Potassium(K)Table 2: The supply of sodium and potassium in theconsumed daily food rations in individual monthsof the study.Studymonthin January and June, respectively. The lowestpotassium content was also observed in January,while the highest potassium content wasmeasured in November.The adequate intake (AI) is 1,500 mg/individual/day for sodium and 4,700 mg individual/day forpotassium [9].Comparison of the obtained contents of analyzedelements with the adequate intake valuesrevealed that the sodium content in the dispensedand consumed DFRs exceeded the AI bythe factor of 4.7 and 4.2, respectively, while thepotassium content did not cover the adequateintake and accounted for 74% and 65.9% of theAI value for the dispensed and consumed rations,respectively. Sodium and potassium content ofdietary food rations was determined for differentpopulations, including students of variousPolish universities. Studies conducted by otherauthors regarding the sodium and potassiumcontent in daily food rations of students of variousuniversities in Poland suggested the adequateintake being exceeded for sodium and not metfor potassium (Table 3) [3, 4, 10, 11, 12].Sodium is added to food products because of itstaste, as well as to enhance other tastes, to preservefood products by inhibiting the growth ofmicroorganisms that make food go bad, and toachieve appropriate food texture. Excess salt is arisk factor of arterial hypertension and its complications(brain stroke, myocardial infarction, circulatoryinsufficiency), as well as atherosclerosis,Table 3: Table 3. Sodium and potassium content of the food rations of students of various universities in Poland.SchoolDepartment ofPharmacy, JagiellonianUniversity MedicalCollegeWarsaw Universityof LifeSciencesMedical Universityof WarsawMedical Universityof BialystokWroclaw Universityof EconomicsPer DFRdispensed forconsumptionYear of thestudy20032004Sodium contentin male students’food rations1940.9 ± 1150.81678.6 ± 1120.8Potassium content inmale students’ foodrations3168.2 ± 1205.72962.8 ± 1284.3Sodium contentin female students’food rations1791.0 ± 1059.71551.0 ± 1032.7Potassium contentin female students’food rations3011 ± 1109.92816 ± 1181.22005 3971 ± 901.2 3277 ± 894.7 3070 ± 991 2789.9 ± 710.12003/2004 3263 ± 1460 3719 ± 1194 2074 ± 860 3089 ± 8192003/20042008/20092008 autumn2008 winterPer DFR actuallyconsumed Adequateintake (AI)7,039.4 ± 1097.6 6,271 ± 996.2 1,5003,477.7 ± 637.2 3,099.1 ± 550.6 4,700Mean content of Mean content ofsodium in individualmonthspotassium in individualmonthsNovember 6,686.3 3,880.3December 5,582.7 2,692.2January 4,365.1 2,486.0February 5,627.4 2853.9March 6,716.5 2,855.5April 5,943.7 3,198.3May 6,460.5 3,592.0June 7,168.9 3,449.3July 6,862.9 3,224.83710 ± 16942302 ± 6872981 ± 22413811 ± 24343364 ± 15902115 ± 7163086 ± 13943882 ± 16702110 ± 9702910 ± 11782328 ± 13981789 ± 11412870 ± 14052346 ± 7802599 ± 9692518 ± 933http://military.isl-journals.com63

© Military Pharmacy and Medicine • 2012 • 4 • 64 – 66osteoporosis and some cancer diseases, i.e. majornon-infectious chronic diseases. The World HealthOrganization (WHO) recommends that adult saltintake does not exceed 5 g per individual per day;despite this, actual salt intake in Europe is muchhigher, reaching as much as 8-12 g. [13]. Also inthe US the dietary sodium supply significantlyexceeds the established norms; in years 2007-2008,the average sodium intake was 3,266 mg/d. [14].According to WHO’s recommendations, dailyintake of sodium from all sources should bereduced to less than 2 g of sodium (5 g of salt).This pertains to both the salt content in readymadefood products (cured meat, bread, cheese,processed food, food mixes etc.), and salt addedto food prepared by consumers themselves.Poland is a country with high salt consumption.It is estimated that the intake of sodium chloridein Poland exceeds current WHO’s recommendationof 5 g of salt/day as much as threetimes. A panel study of households conducted in2009 revealed that the [monthly] salt purchasewas 0.26 kg per individual, which translates intodaily intake of 8.5 g. This was only the salt thatwas used in the household for cooking and addingsalt to cured meat, vegetables, dairy as wellas to the prepared dishes, such as soups, saucesand meats. Estimation should also include saltcontained in ready-made food products. Resultsof all-Polish studies show that cured meat, bread,processed food and frozen food delivers another4.4 g of salt per day. For comparison, the dailyOriginal articleintake of sodium in Belgium is 4.15 ± 1.01 g/day(3.8 ± 1.2 – 4.9 ± 1.2 g) [15].Considering the high intake of salt and itsadverse health effects, programs aimed at reducingthe sodium chloride intake were initiated inmany countries. In Finland, where the programto reduce the salt intake has been in place since1975, the average salt intake was reduced from12.0 g to 9.3 g/d in males and from 9.3 to 6,8 g/din females. A similar trend was observed in theUnited Kingdom, where a program to reduce saltconsumption was introduced in 2003. A reductionin the salt intake from 9.5 g to 8.6 g/d wasobserved by 2008 [16].Conclusions1) The content of sodium in both rations dispensedfor consumption and actually consumedby students exceeded the adequate intake normsseveral times which, upon long-term intake,might be a cause of diet-dependent civilizationmetabolic diseases.2) The potassium content of daily food rationswas lower than the standard value.3) Far-flung activities should be undertaken toraise the health awareness regarding the adverseeffects of dietary salt on human body in bothpersonnel responsible for planning and providingstudents’ board and the MSFS students.References:1. Diet, nutrition and the prevention of chronic diseases.Report of a Joint WHO/FAO Expert Consultation.World Health Organization, Geneva 2003.2. Brzozowska A.: Składniki mineralne w żywieniuczłowieka. W Gawęcki J., Hryniewiecki L.: ŻywienieCzłowieka . Podstawy Nauki o Żywieniu. PWNWarszawa,2000.3. Paśko P., Krośniak M., Chłopicka J., Zagrodzki I.,Zachwieja Z.: Ocena sposobu żywienia studentówWydziału Farmacji Collegium Medium UniwersytetuJagiellońskiego w latach 2003-2004 Żyw. Człow.Metab. 2005, supl.1 660-667.4. Czapska D., Ostrowska L., Stefańska E., KarczewskiJ.: Ocena zawartości wybranych składnikówmineralnych w całodziennych racjach pokarmowychstudentów Uczelni Medycznej w latach 2003/2004 i2008/2009. Brom. Chem. Toksykol. 2009, 3, 725-727.5. Górnicka M., Gronowska-Senger A.: Jakośćwyżywienia wybranymi składnikami mineralnymiw gospodarstwach domowych. Żyw. Człow. Metab.2005, supl. 1, 9-17.6. Rutkowska U. Wybrane metody badania składu iwartości odżywczej żywności. PZWL W-wa 1983.7. Poradnik użytkownika GBC SCIENTIFIC EquipmentPty Ltd 1996.8. Patrie A., Sabin C.: Statystyka Medyczna w zarysie.PZWL Warszawa 2006.9. Jarosz M., Szponar L., Rychlik E.: Woda i Elektrolity.w: Jarosz M., Bułhak-Jachymczyk B. Normy żywieniaczłowieka. Podstawy prewencji otyłości i choróbniezakaźnych., PZWL, Warszawa 2008.10. Przysiężna E., Wasilewska A.: Realizacja normżywieniowych na wybrane składniki mineralne igrupy produktów spożywczych w dietach studentówAkademii Ekonomicznej we Wrocławiu. Bromat.Chem. Toksykol. 2008, 2, 151-159.64 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 65 – 6611. Bujko J., Myszkowska-Ryciak J., Nitka I.; Ocenaspożycia składników mineralnych wśród studentówSGGW w Warszawie. Żyw. Człow. Metab 2005,supl 1. 655-667.12. Ziółkowska A., Ostrowska A.: Porównanie spozyciawybranych pierwiastków w całodziennych racjachpokarmowych warszawskich studentów medycyny wlatach 2001-2004. Żyw. Człow. Metab. 2005,supl 1, 646-650.13. Busch J et al. (2010). Salt reduction and the consumerperspective. New Food 2/10:36-39.Jerzy Bertrandt at al.: Sodium and potassium content of daily food rations …14. US Department of Health and Human Services,US Department of Agriculture. Dietary guidelinesfor Americans, 2010. 7th ed. Washington DC: USDepartment of Health and Human Services, USDepartment of Agriculture; 2011.15. Sekuła W.: Badania indywidualnego spożyciażywności. 2010, www.gis.gov.pl.16. Bibbins-Domingo K et al. (2010). Projected effectof dietary salt reductions on future cardiovasculardisease. New England Journal of Medicine362(7):590-599.http://military.isl-journals.com65

© Military Pharmacy and Medicine • 2012 • 4 • 67 – 76Radosław Ziemba: Cardiac arrest under special … Part II: poisoning …Emergency MedicineCardiac arrest under special circumstances.Part II: poisoning, …, anaphylactic reaction, …,traumatic injuriesRadosław ZiembaMilitary Centre for Pharmacy and Medical Technology in Celestynow, PolandAuthor’s address:Radosław Ziemba, Military Centre of Pharmacy and Medical Technique, ul. Wojska Polskiego 57,05–430 Celestynów, Poland; e–mail: zx11@op.plReceived: 2012.07.20 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:In this publication, we discuss several issues related to cardiac arrest occurring under special circumstancessuch as: hypothermia, near drowning, poisoning, pregnancy, electric shock, anaphylactic reaction,episode of acute, severe asthma, traumatic injuries.Key words: Safar’s ABC scheme, resuscitation, rescue, dealing with an unconscious person.IntroductionThis publication is a continuance of an articletitled Cardiac arrest under special circumstances.Part I: hypothermia, near drowning published inthe previous number of Military Pharmaceuticsand Medicine (Issue V, No. 3). In this section,we discussed the rules of management of cardiacarrest due to: poisoning, pregnancy, electricshock, anaphylactic reaction, acute episode ofsevere asthma and traumatic injuries.Drug overdose and poisoningPoisoning rarely leads to cardiac arrest, but isone of the main causes of death in people under40 years of age. It is also the most frequent causeof non-traumatic coma in this age group. Suicidalpoisoning with medicaments or addictivesubstances constitutes the main reason for hospitalizations.Accidental poisoning is most commonamong children. Criminal poisoning is rare.At times, it is not possible to immediately statehttp://military.isl-journals.comwhether loss of consciousness or cardiac arrestis a result of poisoning. Therefore, this cause ofcome is important to exclude.Large-scale exposition to chemicals or radiationmay occur as a consequence of industrial accidentsor warfare. In such cases, it is importantthat rescue services are not exposed to dangersof contamination. Proper personal protectiveequipment should be used. Decontaminationand transporting victims into safer areas is usuallythe task of special services.ResuscitationThe basics of suicidal poisoning management(“overdose”) involve supportive treatment basedon the ABC scheme directed at preventing circulatoryand respiratory arrest in hope that, in time,the substance will be eliminated from the system.Airway occlusion and respiratory arrest secondaryto disrupted consciousness is a frequent cause67

© Military Pharmacy and Medicine • 2012 • 4 • 68 – 76of death. Suicidal poisonings are often associatedwith excessive alcohol consumption.After clearing the airway and restoring airwaypatency, the presence of respiration and pulseis checked. Mouth-to-mouth ventilation shouldnot be performed when dealing with poisoningsdue to agents such as cyanides, hydrogen sulfide,corrosives or organophosphorous substances.Patient’s lungs are ventilated through a pocketmask or a facemask set using the highest possibleoxygen concentrations. Precautions shouldbe taken in paraquat poisoning, as high oxygenconcentrations can exacerbate lung damage.Aspiration of stomach content to the lungsoccurs in a considerable proportion of poisonings.Therefore, unconscious patients withoutpharyngeal reflexes should be intubated early.So-called fast induction with cricoid cartilagecompression is performed in order to reduce therisk of aspiration. Preferentially, it should be performedby a trained anesthesiologist or a personwith appropriate experience.BLS and ALS should be commenced during cardiacarrest. Pulseless electrical activity (PEA)usually results from use of medicines exertingnegative inotropic effect, but is associated withbetter prognosis than PEA from primary cardiaccauses. Cardioversion is indicated in life-threateningtachyarrhythmias with the exception ofTorsades de Pointes (look below).Drug hypotension is a frequent phenomenon insuicidal poisoning. It usually responds to fillingof vascular bed with fluids, although it sometimesrequires use of inotropic drugs.During resuscitation, we must undertake actionsto identify the poison (or poisons). Patient’s relatives,friends and the ambulance team can usuallyprovide important information. Physicalexamination can reveal diagnostic clues (smell,puncture marks, tablets left in the oral cavity).Specific therapeutic actionsIn poisoning management, we can formulatefew specific therapeutic guidelines usefulin emergency situations. Particular emphasisshould be put on maintenance of vital functions,Review articleoxygenation, compensating acid-base and electrolyteimbalances.Gastric lavage with addition of activated carbonis justified up to 1 hour after poison ingestion. Itis usually performed following intubation. Lategastric lavage exerts little influence on poisonabsorption and can even induce its movementfurther along the gastrointestinal tract. Eliminationof poison from the system can be acceleratedthrough hemodialysis or hemoperfusion.Effective specific antidotes include:1) N-acetylcysteine in paracetamol poisoning;2) high doses of atropine in organophosphorousinsecticide poisoning;3) sodium nitrate, sodium thiosulfate or EDTAin cyanide poisoning, digoxin-specific antibodiesin digoxin poisoning;4) flumazenil in benzodiazepine poisoning,naloxone in opioid overdose.Tricyclic antidepressantsSuicidal tricyclic antidepressant overdosesare frequent and may lead to convulsions andarrhythmias. Threat to patient’s life exists withinthe first 6 hours following ingestion. Widening ofQRS complexes (over 0.16 seconds) indicates elevatedrisk of arrhythmias. Sodium bicarbonatecan provide some cardiac protection and preventarrhythmias in high-risk patients.OpiatesOpiate overdose causes respiratory depression,pinpoint constriction of pupils and coma.Pethidine overdose may result in convulsions.Naloxone is a specific opiate antagonist. Therecommended dose is 0.4-0.8 mg i.v. (drug isadministered slowly in the amount that is neededto obtained an effect) or 0.8 to 1.2 mg in anintramuscular or subcutaneous injection (whichis easier in drug abusers with difficult venousaccess). Time of action of naloxone is shorter (45-70 minutes) than opiates (up to several hours),necessitating administration of additional dosesat times.CocaineThe following may occur in cocaine poisoningdue to excessive sympathetic stimulation:68 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 69 – 76Radosław Ziemba: Cardiac arrest under special … Part II: poisoning …tachycardia, hypertensive crisis and cardiacischemia. Small doses of benzodiazepines (midazolam,diazepam, lorazepam) constitute firstlinetreatment. Nitrates are used as second-linetreatment – they counteract cardiac ischemia.Tachycardia and sudden blood pressure elevationcaused by toxic effect of cocaine can be alleviatedby labetalol (alfa and beta receptor blocker).Drug-induced bradycardiasThey may respond to intravenous atropine atdoses that do not exceed 3 mg (although higherdoses are needed in organophosphate poisoning)or temporary external electrostimulation. Glucagoncan be used in bradycardia induced by betablockers,improving cardiac contractility andincreasing the heart rate.Torsades de PointesThis phenomenon is associated with toxicity ofvarious substances administered for therapeuticor suicidal purposes. The most important principlesof management of such cases include intravenousadministration of magnesium, correctionof electrolyte imbalance and overdrive pacing.Further management and prognosisPersisting loss of consciousness without changingbody position can lead to sore formationand rhabdomyolysis. Electrolyte (particularlypotassium) and glucose concentrations, as wellas arterial blood gases should be closely monitored.Body temperature should also be overseen,as disturbances of thermoregulation occur frequently.Overdose of some substances may leadto either hypo – or hyperthermia. It is importantto preserve blood and urine samples for furtherbiochemical tests. We should be constantly preparedfor prolonged resuscitation, particularly inyoung people, as the poison can be metabolizedor excreted during that time.PregnancyResuscitation of a pregnant woman involves twopeople. However, the emphasis is put on effectiveactions aimed at saving the life of a mother.At the same time, it is the best mode of action tomaintain the wellbeing of a fetus. Sudden cardiacarrest in a mother is most often associated withhttp://military.isl-journals.comchanges occurring in woman’s organism in thethird trimester of pregnancy. Causes of cardiacarrest in a mother include bleeding, pulmonaryembolism, amniotic fluid embolism, prematureplacental detachment, eclampsia and drug toxicity.Cooperation with an obstetrician and a neonatologistshould be established early.Course of resuscitationAll rules of BLS and ALS apply to pregnantpatients. Delayed stomach emptying occurs inthe first trimester of pregnancy, which increasesthe risk of aspiration of gastric contents. Therefore,early intubation is recommended, preferablywith an assistant applying pressure on cricoidcartilage. Intubation may be sometimes difficultdue to anatomical changes taking place duringpregnancy (short and wide neck, large mammaryglands, edema of epiglottis). Diaphragm is elevatedand its mobility is reduced by the enlargeduterus during the last trimester of pregnancyand higher ventilation pressures are required foreffective ventilation.In order to improve venous return and cardiacoutput, it is necessary to reduce the pressureexerted by the uterus on inferior vena cava andaorta (aortocaval compression) through:1) placing a sand-filled sac, a pillow or a prefabricatedwedge (Cardiff type) under the rightbuttock and lumbar area;2) manually moving the uterus leftward;3) tilting the patient to the left on an operatingtable or a long board.Chest compressions are performed in a standardmanner, although they are more difficult toexecute due to mammary gland enlargement anddiaphragmatic stiffening.Circulating blood volume in a pregnant womanis large, but cardiac arrest may occur as a resultof hypovolemia due to an occult internal hemorrhage.Blood is drawn for cross matching andintravenous fluid administration is commenced.Early surgical treatment aimed at stopping thehemorrhage is of most importance.ArrhythmiasCardiac arrhythmias are treated according tostandard management schemes.69

© Military Pharmacy and Medicine • 2012 • 4 • 70 – 76Further managementImmediate cesarean section is indicated followingfive minutes of ineffective resuscitation,improving the likelihood of survival of themother as well as the fetus. It is a difficult decision,but it must be made without unnecessarydelay. Extraction of a fetus removes the aortocavalcompression. ALS should be continuedduring and after the operation.Electric shockElectric shock can occur at home, in a factory oras a result of a lightning strike. Most traumaticinjuries caused by electricity in adults take placeat work. On the other hand, children exposed tothe greatest risk at home. In any given moment,there are 2000 thunderstorms around the globeand 1000 people around the world die because ofit every year.Severity of injury caused by electricity dependson the type of current (alternating or direct), itsvoltage, amount of energy it produces, resistanceto current flow, path of the current through thepatient as well as the surface area and time ofcontact. Skin resistance decreases due to moisture,increasing the likelihood of injury.Contact with alternating current can lead totetanic skeletal muscle spasm. It prevents detachmentfrom the source of current and may lead torespiratory arrest. Alternating current is able toinduce ventricular fibrillation if it acts on a cardiacmuscle during a vulnerable period, analogouslyto a phenomenon called R-on-T. Sometimes,electrical current causes cardiac ischemiadue to coronary artery constriction. Flow of currentacross the chest (from one upper limb toanother) is more often fatal than a vertical flowpath (from an arm to a foot) or astride (fromone foot to another). Diffuse tissue damage mayoccur on the path the flowing current.A lightening strike causes acute and massivedischarge of DC current, leading to depolarizationof the entire cardiac muscle. It poses athreat of asystole or ventricular fibrillation. Dueto heart’s automatism, hemodynamically effectivesinus rhythm returns sometimes. Respiratorymuscle paresis may be the reason for respiratoryarrest and secondary cardiac arrest occursReview articleif appropriate actions are not taken. Lightningmay also cause diffuse neurological damage,including encephalopathy and peripheralnerve damage.DiagnosisCircumstances of an accident are not always clearto a rescuer and he should pay special attention tothe presence of contact burns at the point of currententrance and exit.Rescue actionsThe rescue team must make sure that all sourcesof electrical current are turned off and cannotapproach the victim until it is completely safe.One should remember that high-voltage current(higher than that in home power outlets) mightflow through the ground within a diameter fewmeters from the victim. On the other hand, itis safe to approach victims of a lightning strike,although it is reasonable to move them to a saferplace.Course of resuscitationBLS and ALS should be commenced immediately.Restoration of airway patency is sometimesdifficult if there are electrical burns around theface and neck. In such cases, early intubationshould be performed, as diffuse soft tissue edemadevelops quickly, leading to airway obstruction.Electrocution can result in head and vertebralinjury. Therefore, the vertebra should be immobilizeduntil full clinical assessment. Muscleparesis, especially following high-voltage currentdischarge (industrial conditions), can persist upto 30 minutes and ventilatory support may benecessary during that time.The most common initial arrhythmia followinghigh-voltage alternating current dischargeis ventricular fibrillation, which needs to betreated with a defibrillation attempt. Direct currentdischarge more frequently leads to asystole.Standard management should be undertaken inarrhythmias. Smoldering clothing and footwearshould be removed in order to avoid furtherthermal damage. In case of diffuse tissue injury,it is sometimes necessary to commence intenseintravenous fluid resuscitation. It is important tomaintain proper urine excretion, which enables70 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 71 – 76systemic excretion of myoglobin, potassium andother products released by damaged tissues.Patients with serious thermal injuries oftenrequire surgical intervention.Further management and prognosisImmediate commencement of resuscitation inyoung patients with cardiac arrest caused by electricshock often brings positive outcome. Thereare reports of effective resuscitation even afterprolonged ALS. All patients after serious electricshock and patients with circulatory or respiratoryproblems, loss of consciousness, cardiac arrest,electrocardiographic abnormalities, soft tissueinjuries and burns require hospital monitoring.Anaphylactic shockIt seems that phenomena related to anaphylaxisare increasingly more common. It is certainlyassociated with growing frequency of allergiesover the course of two or three past decades.Radosław Ziemba: Cardiac arrest under special … Part II: poisoning …blood pressure and are rarely caused by primaryheart disease or intravenous administration ofadrenaline. Anaphylactic reactions present withvarious degrees of severity and can developquickly, slowly or, rarely, in a biphasic manner.Rarely, symptoms may be delayed (it happens incase of latex allergies) or persist over 24 hours.Such reactions may be associated with expositionto various agents. The most frequent causesinclude insect bites, reactions to drugs, contrastagents or some foods. Peanut and hazelnut allergiesare particularly dangerous.Muscle relaxants can induce anaphylaxis andanesthetic agents constitute an important causeof anaphylactoid reactions. Absence of establishedsymptoms and wide scope of clinical picturecan pose diagnostic difficulties. In any case,it is necessary to acquire full medical history(with particular focus on past allergic reactions)and perform physical examination. Special attentionshould be paid to the condition of the skin,heart rate, blood pressure, upper airways andauscultation.Diagnosis of anaphylactic reactionsThere is no generally accepted definition of anaphylacticreaction. The term “anaphylaxis” usuallyrefers to immoglobulin E (IgE)-mediatedhypersensitivity reactions occurring in typicalsituations. Anaphylactoid reactions are similar,but are not associated with hypersensitivity. Forsimplicity, we will use the term anaphylaxis forboth types of reactions unless they are clearlydistinguished. Their symptoms and managementare similar, so this distinction is only importantwhen considering further treatment. Bothof those reactions may be associated with variousdegrees of angioedema, urticaria, dyspneaand hypotension. Some patients die due to acute,irreversible bronchospasm or laryngeal edema.Among other symptoms are the following: rhinitis,conjunctivitis, abdominal pain, vomiting,diarrhea, sense of unrest. There is usually skindiscoloration: patient’s face becomes red or pale.Cardiovascular depression is a common symptom,particularly when it comes to reactions tointravenous agents or insect stings. It is caused byvascular dilatation and movement of plasma intothe extravascular space. Circulatory failure orarrhythmias are associated mainly with a drop inhttp://military.isl-journals.comIf possible, peak expiratory flow should be measuredand documented. Distinguishing betweenanaphylaxis, panic attack or vasovagal episodecan be sometimes difficult. All of these phenomenacan occur, e.g. after vaccination. Full clinicalassessment facilitates making this distinction.Comments on managementThere is a common agreement that adrenaline isthe most important drug used in managementof anaphylactic reactions. As an alfa receptorantagonist, it abolishes peripheral vessel dilatationand reduces the edema. Its activity towardbeta-receptors causes airway dilatation, increasescontractility of cardiac muscle and inhibits histamineand leukotriene release.Adrenaline is most effective if administeredimmediately after the occurrence of a reaction,but is not devoid of risk, particularly when givenintravenously. Intramuscular adrenaline is avery safe drug. Undesirable effects are incrediblyrare and the only case of myocardial infarctionfollowing its intramuscular administrationinvolved a patient with high risk of coronaryartery disease. At times, there is doubt whetherthe complication (e.g. myocardial ischemia) is a71

© Military Pharmacy and Medicine • 2012 • 4 • 72 – 76result of the allergen itself or adrenaline administeredfor therapeutic purposes.In rare cases adrenaline may fail to abolish clinicalsymptoms of anaphylaxis, particularly in latereactions or in patients treated with beta-blockers.In such instance, other means of managementgrow in significance, especially replenishingof circulating blood volume. Antihistamines(H receptor blockers) should be routinely used inall cases of anaphylactic reaction, which facilitatesattenuation of vasodilatation occurring asan effect of histamine action. These drugs maynot be effective in some anaphylactoid reactionsthat are partially induced by other mediators, buttheir use is safe. It should be emphasized that useof antihistamines only may not be sufficient forsaving patient’s life. Administration of H2 receptorblockers should also be considered.Corticosteroids are thought to work too slowly, asthe effect of their administration may appear aslong as 4-6 hours following intravenous administration.However, they may help in immediatecontrol of an acute episode and play a significantrole in prevention or shortening the time of prolongedreactions.ResuscitationAll victims should be placed in a comfortable,supine position. Suspected allergen is removed(e.g. drug infusion or blood transfusion). Supineposition with or without leg elevation may facilitatecorrection of hypotension, but makes breathingdifficult. If conditions allow, high-flow oxygenshould be administered (10-15 l/min).BLS or ALS is commenced in case of cardiacarrest. During resuscitation, it may be necessaryto administer higher doses of adrenaline. Infusionof large amounts of fluids is sometimes necessary.In all patients with clinical signs of shock, airwayedema or apparent breathing disturbances,adrenaline should be administered intramuscularly,which accelerates its absorption. Signs suchas inspiratory wheezing, rhonchi, cyanosis, severetachycardia and poor capillary return shouldevoke a suspicion of severe reaction. Adultsshould receive 0.5 ml of adrenaline in a 1:1000(500 micrograms) solution. This dose should berepeated after about 5 minutes if clinical signsReview articlepersist or become more severe (particularly whendisturbances of consciousness are present as aresult of hypotension). In many cases there maybe a necessity of administering several doses,especially when improvement is short-lasting.Intravenous administration of adrenaline in a1:10 000 (under no circumstances should it be1:1000) solution is associated with complicationsand it should be reserved for patients in deepshock posing an immediate threat to life, and tospecial situations, e.g. during anesthesia. Evengreater dilution of adrenaline in a ratio of 1: 100000 allows for more precise dosing and increasesthe safety, as the risk of unwanted effects isreduced. This drug is given under constant heartrate and ECG supervision, which constitutesthe minimum monitoring. Doctors experiencedat intravenous adrenaline administration maychoose this route of administration in patientswith signs of severe anaphylaxis.Airway occlusion may occur as a result of soft tissueedema. Early intubation should be performedin such cases. Any delay can make it extremelydifficult. Antihistamine drug acting on H1receptors [e.g. dimetindene (Fenistil®)] should beadministered in slow intravenous injection, butH2 blockers can also be used (e.g. ranitidine).Hydrocortisone (sodium succinate preparation)should be used following a severe episodeand prevents the late sequelae from occurring.It is particularly important for patients sufferingfrom asthma (who are at greater risk of severe oreven fatal anaphylaxis) if they were treated withcorticosteroids before. Hydrocortisone is administeredin a slow intravenous injection. Fluidinfusion should be commenced if there is significantblood pressure reduction and patient doesnot respond quickly to administered medicines.Anaphylactic reactions in adults –treatment by first-aid providersPatients who suffered an episode of anaphylaxis,even of moderate degree, should be warnedagainst the possibility of early return of symptomsand, in some circumstances, they needto be hospitalized for observation for next 8-24hours. It refers especially to cases of:1) severe reactions with slow onset – evidenceof idiopathic anaphylaxis,72 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 73 – 762) reactions in patients with severe asthma orstrong asthmatic component,3) reactions associated with the possibility ofcontinuous exposure to the allergen,4) patients who underwent biphasic reactionsin the past.If there is bronchospasm not responding to standardmanagement, inhalation of beta-2 receptorantagonist, e.g. salbutamol, may be of some help.Additional tests and further managementMeasuring mast cell tryptase levels can retrospectivelyfacilitate the diagnosis of anaphylaxis.Ten milliliters of blood should be drawn to a tubecontaining clot activator between 45 minutes to 6hours after the episode.Radosław Ziemba: Cardiac arrest under special … Part II: poisoning …Cardiac arrest in patients with severe asthmamay occur as a result of:1) hypoxia due to severe bronchospasm andairway obstruction by secretions;2) arrhythmias due to hypoxia or beta receptoragonist and aminophylline toxicity;3) tension pneumothorax.Life-threatening asthmatic episode is recognizedbased on the absence of breath sounds, cyanosisand poor respiratory drive. It may be accompaniedby bradycardia and hypotension. Patientappears exhausted, confused or falls into a coma.Arterial blood gas measurement reveals hypoxia,acidosis accompanied by normal or elevated carbondioxide partial pressures.Acute managementFollowing successful management of anaphylacticreaction, it is important to identify the allergenin order to avoid recurrence of the conditionin the future. Therefore, patient should bereferred to a specialist outpatient clinic. Patientsat great risk of anaphylactic reaction can keep atall times a special, adrenaline-filled syringe forself-administration and wear a warning bracelet.Acute episode of severe asthmaAcute episode of severe asthma is almost alwaysa reversible state and we must assume that suchpatients can be saved. The majority of deathsoccur outside of the hospital. Several factors contributeto it, such as:1) patient and his relatives do not recognizethe severity of asthmatic episode and turn tomedical help too late;2) emergency services and family doctors donot always act fast enough;3) patients with mild asthmatic episodes aredischarged home after being provided withmedical assistance and suffer from suddendeterioration of their condition.It is important to treat all asthmatic exacerbationsaggressively in order to prevent futurelife-threatening recurrences and cardiac arrest.National guidelines were published on managementof acute asthma exacerbations based onearly oxygen administration, use of beta-2 receptorblockers (salbutamol), corticosteroids andaminophylline.http://military.isl-journals.comPatient status will quickly deteriorate, leading torespiratory arrest and secondary cardiac arrestif proper management is not immediately commenced.Such patient should be quickly movedto a facility where proper care and monitoringis available. High oxygen concentrations areadministered. First-line therapy in acute asthmais inhalation of beta-2 agonists. It usually beginswith administration of salbutamol (5 mg in 5 mlof saline) in nebulization mixed with oxygen, orin 4-6 puffs using an inhaler with a spacer. Thisdose can be repeated at 15-minute intervals or,if necessary, it can be administered continuously.Corticosteroid therapy should be commenced atan early stage (during first 30 minutes). Prednisoloneat a dose of 30-60 mg orally, 200 mg ofhydrocortisone i.v. or both drugs should be givenif patient’s condition is very severe.If this treatment gives no effects, subcutaneousadministration of adrenaline (0.3 mg) can preventthe necessity of artificial ventilation. Thesame dose of adrenaline (0.3 mg) can be repeatedtwice in 20-minute intervals.If drugs administered so far are not effective,other actions are taken such as: inhalations withanticholinergic drugs (ipratropium 0.5 mg innebulization), intravenous infusion of aminophylline(5 mg/kg infusion in 30-45 minutes),intravenous magnesium sulfate (2-3g) or administrationof a breathing mixture containinghelium and oxygen in a 70:30 ratio. Performingchest x-ray examination early is instrumental.73

© Military Pharmacy and Medicine • 2012 • 4 • 74 – 76Such patients often suffer from substantial dehydrationand intravenous infusion of fluids isbeneficial.Mechanical ventilation is only considered whenall conservative methods fail. Decision regardingcommencement of mechanical ventilation shouldbe based on the degree of patient exhaustion, noton blood gas analysis. Noninvasive ventilationmay prevent the necessity of tracheal intubationand invasive mechanical ventilation.Achieving normal blood gas values duringmechanical ventilation can be difficult due tohigh airway resistance. It is sometimes necessaryto use special techniques of assisted ventilationwith patient sedation (e.g. using anesthetic gasesor ketamine).ResuscitationBLS and ALS rules apply during cardiac arrest.However, there are some additional requirements,which should be remembered: patientventilation is sometimes difficult due to high airwayresistance. Under such circumstances, ventilationwith a facemask is associated with highrisk of stomach distension. Therefore, it is importantto perform tracheal intubation early. Highairway pressures necessary to maintain properminute ventilation increase the risk of tensionpneumothorax. Prolonging inspiration and expirationtime is often necessary in order to avoidincrease in intrinsic end-expiratory pressure(i-PEEP or auto PEEP). Indirect cardiac massageis difficult or impossible in a patient with hyperinflatedchest. Prolonging the expiration timemay partially overcome this difficulty. If experiencedpersonnel is present, opening of thoraciccavity for direct cardiac massage should be considered.Arrhythmias are treated according tostandard therapeutic schemes.Traumatic injuriesCardiac arrest secondary to blunt trauma is associatedwith very poor prognosis. In cases of cardiacarrest after penetrating trauma, patient canbe sometimes saved if conditions for undertakingtherapy by personnel experienced in directcardiac massage (with opening of thoracic cavity)are met.Review articleCauses of cardiac arrest following trauma include:1) severe brain injury,2) hypovolemia due to massive blood loss,3) hypoxia secondary to respiratory arrest,4) direct injury to vital organs (heart or greatvessels),5) comorbidities (e.g. cardiac arrest in a driver,which preceded the traffic accident),6) tension pneumothorax,7) cardiac tamponade.ResuscitationEarly assessment and commencement of appropriateactions can prevent cardiac arrest. It isimportant to identify and undertake appropriatemanagement of life-threatening injuries as soonas they are diagnosed. Fast transport to a hospitalis crucial, as immediate surgery is often necessary.Rules of BLS and ALS in trauma patients arethe same as in cardiac arrest due to other causes.However, one should remember that: cervicalspine should be protected during restoration ofairway patency.It is important to exclude the presence of tensionpneumothorax. This complication may be indicatedby worsening lung compliance or hyperresonantpercussion sound. In such instance,pleural cavity should be immediately puncturedwith a needle (in the second intercostal space, inthe midclavicular line).Pulseless electrical activity (PEA) due to hypoxia,hypovolemia or both, constitutes the most commonmechanism of cardiac arrest in traumapatients. Therefore, administration of 100% oxygen,replacement of circulating blood volume orattempt at stopping the hemorrhage (direct compression,surgery) are necessary.Thoracic cavity can be opened in a small proportionof patients with penetrating chest traumaand PEA in order to commence direct cardiacmassage and simultaneous management of cardiactamponade and control of hemorrhage.Immediate and proper management of the discussedconditions can prevent occurrence of cardiacarrest. Resuscitation method may have to bemodified if cardiac arrest takes place in specialsituations described above.74 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 75 – 76Radosław Ziemba: Cardiac arrest under special … Part II: poisoning …References:1. R.G. Wilcox: How to cope with cardiac arrest.Żródło: http://www.libramed.com.pl/wpg/NumeryArchiwalne/05/04.html2. Marzena Wojewódzka-Żelezniakowicz, SławomirLech Czaban, Piotr Szczesiul, Anna Nielepiec-Jałosińska, Jerzy Robert Ładny: Hipotermiaporesuscytacyjna – wskazania, sposób prowadzenia,skuteczność kliniczna, powikłania stosowania,Postępy Nauk Medycznych, 12/20093. White L. Audit of cardiac arrest procedure andoutcome. A thesis submitted in partial fulfilment ofthe requirements for the degree of Bachelor MedicalSciences, University of Nottingham Medical School1992.4. European Resusciation Council Working Party,Adult advanced cardiac life support: the EuropeanResuscitation Council Guidelines 1992 (abridged).BMJ1993; 306: 15895. Niemann JT. Cardiopulmonary resuscitation. N Engl JMed. 1992; 327: 1075-1080.6. Praca zbiorowa Anestezjologia i intensywna opieka,red. Laura Wołowicka, Danuta Dyk, WydawnictwoLekarskie PZWL, 2008.http://military.isl-journals.com75

© Military Pharmacy and Medicine • 2012 • 4 • 77 – 80Łukasz Szarpak, Dariusz Timler: Prevalence of atrial fibrillation in emergency Original article …Emergency medicinePrevalence of atrial fibrillation in emergency medicine practiceŁukasz Szarpak 1 , Dariusz Timler 21Collegium Masoviense – College of Health Sciences in Żyrardów, Poland2The Institute of Emergency and Catastrophe Medicine, Medical University of Lodz, PolandAuthor’s address:Łukasz Szarpak, Collegium Masoviense–College of Health Science, ul. G. Narutowicza 35, 96-300 Żyrardów,Poland; phone: (+48) 500 186 225, e–mail: lukasz.szarpak@gmail.comReceived: 2012.08.12 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Introduction: Atrial fibrillation is a condition of heterogeneous etiology and diverse clinical picture. It isa challenge for the system of Emergency Services.Aim of the study: The aim of this study was to analyze selected epidemiological data of patients withatrial fibrillation treated at the Emergency Department of the M. Kopernik Provincial Specialist Hospitalin Lodz between 01.2010 and 12.2010.Material and methods: Study included 422 patients with atrial fibrillation (237 women and 185 men)aged 25 to 96 years (mean age — 73.51 years).Results: Atrial fibrillation was more common in women than in men (56% vs. 44%). Mean age washigher in the female than the male population (76.5 vs. 69.3 years). The majority of medical interventionsconcerned patients aged 80-89 years.Conclusions: In our material, atrial fibrillation involved mainly patients older than 70 years. Atrial fibrillationis more common in women than in men. Atrial fibrillation occurs most often during winter season,between 10 and 12 o’clock.Key words: atrial fibrillation, seasonality, medical emergency response team.IntroductionDespite considerable advancements in the diagnosticsand treatment that took place in therecent few years, atrial fibrillation (AF) still posesa serious clinical and social problem [1]. It is themost common form of arrhythmia encounteredby the Medical Emergency Response Teams [2].According to the guidelines of European Societyof Cardiology, atrial fibrillation is a type ofarrhythmia that presents on an ECG as absoluterhythm irregularity, i.e. completely irregular RRintervals. Moreover, there are no discernible Pwaves on an ECG, atrial cycle length betweenhttp://military.isl-journals.comthe following atrial activations is variable andless than 200 ms, leading to hemodynamic disturbances[2, 3]. These changes often result fromirregular and excessive ventricular rates as wellas atrioventricular dyssynchrony.Prevalence of AF in general population is estimatedat 0.4-1.0% and increases with age, reaching8% in people over 80 years old. Median ageof patients with AF is about 75 years. Results ofprospective studies indicate that yearly incidenceof AF increases with age from less than 0.1% inpeople below 40 years old, to 1.5% in women and2% in men above 80 years old [3].77

© Military Pharmacy and Medicine • 2012 • 4 • 78 – 80Aim of the studyThe goal of the study was to assess selected epidemiologicalparameters associated with atrialfibrillation among patients of hospital EmergencyDepartment (ED).Material and methodsIn this study we retrospectively analyzed patientswith atrial fibrillation treated at the EmergencyDepartment of M. Kopernik Provincial SpecialistHospital between 01.01.2010 and 31.12.2010.Original articledepending on the month of hospitalization (Fig. 3).Most cases of atrial fibrillation were noted in February(n=48; 11%), followed by October (n=39;9%) and April (n=38; 9%). In August (n=29;7%), July (n=30; 7%) and March (n=31; 7%) weobserved a reduction in the number of diagnoses.Statistical analysis revealed significant differencesin the incidence of atrial fibrillation episodesin a yearly cycle (p

© Military Pharmacy and Medicine • 2012 • 4 • 81 – 86Magdalena Cybulska at al.: Autopsy marks on anthropological material …Autopsy marks on anthropological material contributingto research on history of anatomy in PolandHistory of medicineMagdalena Cybulska, Agnieszka Adamczyk, Agnieszka Młudzik, Czesław JesmanHistory of Science and Military Medicine Department, Medical University of Lodz, PolandAuthor’s address:Magdalena Cybulska, History of Science and Military Medicine Department, Medical University of Lodz,ul. Żeligowskiego 7/9, 90-643 Łódź, Poland; phone: (+48) 426393270, e–mail: magdalena.cybulska@umed.lodz.plReceived: 2012.09.19 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:In this publication on the development of anatomical studies in Poland we used anthropological (fromarcheological excavation sites in Poland) as well as written sources. Bone material found in our regionbears signs of removal (sawing off) of the cranial vault. It is difficult to determine whether these autopsieswere judicial or anatomopathological. Few of such skulls were examined, but there is data indicatingthat post-mortem examinations were commenced in the late middle Ages. They were probably notpublic, as such autopsies have been conducted in Poland since the 17 th century. Doctors and barberswere undoubtedly curious what the human body holds. Anatomical textbooks from the middle Agesshowed how to conduct an autopsy. Most skeletons with traces of post-mortem examination are datedto modern times, period of greatest development of surgery and anatomopathology itself. The need foranatomical studies for scientific as well as didactic purposes has been noted since renaissance.Key words: anthropology, anatomopathology, anatomical studies, history of medicine, post-mortemexaminations.Human body, physique and functions of specificorgans have been the subject of interest for doctorsand philosophers since antiquity. Initially, inprehistoric times, people involved in therapeuticscould acquire anatomical knowledge during managementof companions’ wounds and traumaticinjuries. Such information can be also obtainedfrom the corpses of hunted animals. By observinganimal anatomy, the hunters concluded that ahuman must be built in a similar fashion [1].In the ancient Egypt, internal organs wereremoved from the body using special tools duringmummification. However, ancient Egyptians’knowledge on the location of organs in ahuman body was rather ritual and they did nottake advantage of it during treatment. It washttp://military.isl-journals.commainly supposed to preserve the body, so that thedeceased Pharaoh or other official could use itafter death [2].Alcmaeon of Croton (4 th century B.C.) stated, thatphilosophical considerations are not sufficient tounderstand anatomy and post-mortem examinationsare necessary. He performed animal autopsies.Based on his observations, he came to aconclusion that all thoughts and impressions areformed in the brain.Rapid development of anatomical studiesoccurred in the 3 rd century B.C. in Alexandria,which became the focus of the scientific world inthe ancient times. Autopsies as well as vivisectionswere conducted on convicts. Two famous81

© Military Pharmacy and Medicine • 2012 • 4 • 82 – 86anatomists-doctors, Herophilus and Erasistratos,worked there.In the Roman world, autopsies of human remainswere prohibited due to ethnic and religious reasons.Anatomy known from the writings of Galen(a doctor, who lived in the 2 nd century A.D.) isthat of animals: pigs and apes.In the Middle Ages, knowledge of anatomy wasbased on schematic pictures and writings by Hyppocratesand Galen. A papal or royal permissionwas required for performing an autopsy. A humanbeing was considered a microcosmos — reflectionof the surrounding macrocosmos [4].Thanks to artists, painters and sculptors, interestin human physique increased during renaissance.In the history of medicine, the 16th centuryis known as a “century of anatomists.” In 1543,Andreas Vesalius published his work: De humanicorporis fabrica libri septem, where he pointed outtwo hundred of Galen’s errors. This date is consideredthe border between medieval and modernanatomy. Vesalius’ drawings portray the skeletal,cardiovascular systems and musculature, with thecorpse depicted in a vertical position instead oflying down on the examination table [5].At the turn of the 15 th and 16 th century the firstanatomical theaters are created in Padua, Montpellierand Basil. They were particularly numerousin the 17 th century.In this publication, based on anthropologicaldata (acquired from archeological excavationsites), we will try to demonstrate how anatomicalstudies developed in the region of Poland andwhen they were commenced. We will try to comparethese data with written sources. Traces ofpost-mortem examinations found on the skullsand other parts of the skeleton prove that barbersand doctors were interested in how a humanbeing is built.Skulls found during archeological excavationswith openings encompassing the entire or almostentire skull vaults are examples of probable postmortemexaminations. We possess several suchskulls from Poland, but most of them are not preciselydated. It is difficult to unequivocally assesswhether these autopsies were anatomopathologicalor judicial.Review articleNames of the medics appear for the first timein the written sources from 13 th century. Therewere 25 medics and physicians noted during thattime. Wroclaw was the greatest medical centerof the 13 th century. There are several doctorsfrom this city mentioned in the published documents.There were also doctors in Cracow, Legnicaand Poznan. The number of qualified medicsincreased in the 14 th century. Written sourceslist doctors in Cracow, Wroclaw, Glogow, Bytom,Gniezno, Wloclawek as well as in Pomerania.Physicians focused around princely and bishops’courts, as well as Jagiellonian University in the15 th century [6].In the 14 th century, the first post-mortem examinationswere performed in Italy: Padua, Venice,Florence and in France: Montpellier. In renaissance,many artists, including Leonardo daVinci, were interested in studies on human anatomy.His biographers report that he witnessedautopsies in the Santa Maria Novella hospitaland perhaps performed some of them personally.He undertook the trouble to study all stagesof human development, beginning with infancyand ending with senescence. He describedthe skeletal, cardiovascular, nervous systemsand musculature [7].According to the written sources, the first knownpublic autopsy in Poland was performed in 1613in a village called Pruszcz, located near Gdansk,on a deformed newborn baby. In the 16 th century,a gymnasium in Gdansk was the only placewhere regular lectures on anatomy took place. In1580, a separate chair of anatomy and medicinewas formed in Gdansk [8]. The first autopsy wasperformed at the Jagiellonian University in Cracowby Rafal Jozef Czerwiakowski in 18 th century[9]. Thus, written data indicate that post-mortemexaminations were first performed in Poland atthe turn of 17 th and 18 th century.The first skull to be discussed was found inOpole, in a cemetery dated to the 14 th century.Articles by prof. Adam Paluch describe it as atrepanation skull [10, 11]. However, it stands outbetween other trepanation skulls due to orificedimensions and technique of its execution. Thisopening is particularly wide and was performedafter death. The skull was found during excavationsin the Opole Market Square and its features82 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 83 – 86indicate male sex of the deceased. Unfortunately,no postcranial skeleton was found [12].A large bone fragment was removed posthumouslyfrom the skull: a fragment of coronalsuture (coronal suture forms a border of the orifice,suture pattern is visible at the superior margin),part of the right parietal bone and a largefragment of left occipital bone, reaching all theway to the left temporal bone. Opening encompassesalmost entire sagittal suture (a fragmentof sagittal suture is visible as it joins with lambdoidsuture) and has the following dimensions:102x94mm (external lamina) and 95x84mm(internal lamina). Possibly, such large skull fragmentwas removed for bone amulets or a drinkinggoblet (such practice was known in the MiddleAges and previous eras). Thus, this procedurewas performed after persons’ death for magicalreasons. In Middle Ages, bones of the deadand pieces of their clothing were often used formagical or therapeutic purposes. They were usedfor bewitchments. We can present an exampleof such procedure from Lithuania, where fourfemale skulls (14 th -16 th century) were found withround orifices performed posthumously. Bonefragments serving as amulets were acquired thisway [13]. There is a suspicion that in folk medicine,human skull grated into powder, servedwith food or drinks, was considered treatmentfor some aliments [14].There is also another possible explanation. Suchlarge opening was done in order to look insidethe human head and curiosity was the reasonfor post-mortem examination. The margin ofthe orifice is uneven and jagged, particularly onthe right side, while the inferior orifice marginis evenly filed off. Part of calvaria was probablyremoved using a saw (sharp and smooth) and thebone was broken at the coronal suture.A canon from Opole, master Pawel, who servedas a town physician in 1261, was mentioned inpublished documents [15]. Opole lies near Wroclaw,which in the Middle Ages was the focus ofqualified physicians. The doctors acknowledgedin written sources practiced in Cracow, Bytomand Glogow in the 14 th century. Names of doctorswho practiced in Silesia were also preserved:Tomasz — the titular Bishop of Serepta, Jan ofGrodkow, Jan of Glogau. There were two centersMagdalena Cybulska at al.: Autopsy marks on anthropological material …of development of Polish medicine in the 14th-15 th century – Cracow and Wroclaw [9].The second skull in question (also containinga large opening) comes from the St. NicholasChurch in Torun. Skeletons found duringarcheological excavations are dated to 14th and18th century. A large, oval fragment of calvaria,including a fragment of left and right parietalbones and posterior part of frontal bone wereremoved from a male skull. Body of the sternumwas also cut with a sharp instrument, which maybe an evidence of attempted removal of internalorgans [16]. The person performing the autopsywas probably not very experienced in suchmaneuvers. Orifice margins are quite even, thus asharp tool with a smooth blade was possibly usedand tool marks are visible on the edges of theopening. Superior part of the skull (entire cranialvault) was sawn off, while the posterior portion offrontal bone lamina was broken off. In this case,the resected bone was found together with theskull and only the fragment of broken off frontalbone is lacking. The 15 th century documentsmention a doctor who practiced in the region ofTorun. This autopsy may be also related to theactivity of the Academic Gymnasium in Torun,which offered anatomy lectures. This facility wascreated in the 16th century, but its developmentfalls on the period of 17 th century.Similar skulls from 16 th and 18 th century bearingtraces of autopsies (the superior part of calvariawas also removed) were discovered at theexcavation site in Holy Spirit in Brzesc Kujawski(Kujawsko-Pomorskie Province). There were atotal of 5 such skulls excavated at cemeteries nearthe hospital and the church. An iron saw wasprobably used here to remove calvaria [17]. Functioningof the first hospital in Brzesc is dated to13 th -14 th century. Medieval hospitals functionedmainly as shelters, taking care of the poor andill travelers. With time, since renaissance, theygained increasingly more medical character.Another skull, which is an example of post-mortemexamination, was dug out from a cemeteryin Dabrowna (Warmia and Mazury Province)dated to 14 th -17 th century. It belonged to an adultmale. Calvaria was removed (part of frontal bone,large fragments of parietal bones, part of occipitalbone) using a metal saw — the cut ran over thehttp://military.isl-journals.com83

© Military Pharmacy and Medicine • 2012 • 4 • 84 – 86supraorbital arches. Bones were not broken off inthis case [18].Three skeletons found in a cemetery in Sandomierzdated to the end of 18 th and mid-19 th centuryalso wore the signs of post-mortem examinations,as indicated by the marks found on skulls– cut-off cranial vaults as well as rib cuts (thoraciccavity was opened in this fashion). Thepoor and the homeless who died in the hospitalor in prison were buried in this cemetery [19]. Insuch cases autopsy could be performed in orderto identify the cause of death (when it was difficultto determine it otherwise – such autopsieswere judicial) or to train future doctors.These autopsies could be related to the activityof the provincial physician in Sandomierz or theJagiellonian University.Three skulls with removed calvarias were foundduring rescue works conducted in the cemeteryin Wroclaw, which was used from the 2 nd half tothe end of 19 th century. Due to poorly preservedmaterial, it is difficult to draw more precise conclusionswith regard to these remains [20]. Hospitalcare has been developing in Wroclaw sincemedieval times. In the 19 th century, some of Wroclawhospitals contained autopsy rooms [21, 22].Anatomopathological studies developed particularlyrapidly during this period. History of Facultyof Medicine in Wroclaw reaches the beginningsof 19 th century; therefore these autopsiescould be didactic in character.Openings in the skulls collected in Torun,Brzesc Kujawski and Dabrowna are similar inshapes; similar autopsy techniques were usedhere with cranial vaults likely removed using asaw. Skulls found at the two latter sites have calvariasremoved above the supraorbital arches. Incase of the skull found in Opole, this procedurewas conducted carelessly and the orifice is asymmetric.Skulls found in Torun and Dabrownabear cutting marks at the bone edges, indicatinglittle experience of the operator. Skulls fromOpole and Torun bear signs of broken off bonefragments. Since there were hospitals in BrzescKujawski and Dabrowna, they could constitutesources of anatomical knowledge but it is alsopossible that these autopsies were judicial.In the surgical school in Boulogne post-mortemexaminations were conducted as early as in 13 thReview articlecentury. Anatomy handbook by professor ofmedicine, Mondina de Luizzi (1270-1326) fromBoulogne, became the fundamental literatureused for teaching anatomy and autopsies wereperformed based on it. Mondina de Luizzi conductedthe first autopsy in the presence of studentsin 1315 on the corpse of a woman condemned todeath. His publication does not resemble modernanatomy handbooks, which describe specificorgans. It is rather a guide to performing a postmortemexamination and gaining access to theorgans of the abdomen, thoracic cavity and head[23]. One of the illustrations from a book “Anathomia”by Guido da Vigevano (1280-1349) from1345 depicts a doctor performing an autopsy andopening the skull. He removes the skull vault bymaking an incision above supraorbital arches,through parietal bones and occipital bone. Heuses a knife (perhaps a kind of chisel) and a hammer.He hits the end of the knife with a hammerin order to remove the superior portion of theskull [24]. Interestingly, the corpse is depictedin a vertical, not horizontal position (as in thelater work by Vesalius). Six of eighteen illustrationsfrom this handbook concern neuroanatomy.Frontal and sagittal sutures are shown onthe skull; dura mater and brain are also revealed.Guido da Vigevano probably did not distinguishthe arachnoid in his studies [23].Such autopsy technique described in this handbookhad to be widespread. Skulls from Torun,Dabrowno and Brzesc Kujawski bear signs ofautopsies conducted in such manner, althoughthe last incision ran throughout the entire had,from supraorbital arches, through parietal bonesto the occiput. On the skulls from Opole andTorun, incisions were made along coronal sutureor by the posterior part of frontal bone laminaand do not pass through occipital bone. Thistechnique was also used in the skull from Opole,but symmetry was not preserved while cuttingoff the cranial vault.It is worth noting that anthropological materialbearing signs of autopsy was also found duringexcavations in other European countries. Materialfrom England is most often dated to 18 th and19 th century and comes from cemeteries locatedby shelters and hospitals for the poor as well ascemeteries located near medical schools. Bodiesof criminals were often subjected to post-mortemexaminations. Signs of autopsies were noted on84 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 85 – 86Magdalena Cybulska at al.: Autopsy marks on anthropological material …the skulls (removed calvaria), ribs, clavicles andvertebral bodies.Bone marks indicate that autopsies were performedin order to establish the cause of death,but also served the purpose of educating futuredoctors. For example, limb amputations werepracticed on cadavers. Autopsies were conductedon female, male cadavers, but also onbodies of children and fetuses. There is a lot ofanthropological material from 18 th and 19 th centuryLondon showing that autopsies were frequentatthat time [25].Italian anatomist, Giovanni Battista Morgagni(1682-1771) thought that it is a duty of a doctorto perform post-mortem examinations of hispatients. He supposed that disease is localized ina particular organ [4].Great development of anatomical studiesoccurred from the second half of 20 th century,as indicated by anthropological excavation dataas well as written sources. This fact is related toprogress in the field of surgery and anatomopathologyitself. General anesthesia and introductionof antiseptics and aseptics to operatingrooms, improved hemostasis led the surgeons tobroaden the range of procedures and advancedeeper into human tissues. The significance ofanatomopathological studies in clinical medicinewas also emphasized. Doctors linked diseasesymptoms they saw in their patients withanatomopathological picture seen on an autopsytable. Therefore, post-mortem examinationswere supposed to be a way to explain pathologicalchanges. Karl von Rokitansky (1804-1878), aCzech who co-created the new Viennese schoolalso known as anatomopathology school in thehistory of medicine, had great contributions topathological anatomy [4, 26].Modern medical textbooks pertaining to theissue of post-mortem examinations also describecranial opening. Soft tissues should be first separated:skin, dense connective tissue layer, tendinouscap of the epicranial muscle, loose connectivetissue layer and periosteum of calvaria.Incision runs about 2.5 cm above the superiormargin of the orbit and posteriorly about 1 cmabove the external occipital tuberosity. Externallamina is cut with a saw and separated fromthe diploe using a chisel. External and internalhttp://military.isl-journals.comlamina can be also simultaneously cut with anoscillation saw [27]. Therefore, in the medievaltimes soft tissues also had to be removed beforeuncovering the bone. Saws and chisels were usedfor cutting bones.Autopsy techniques evolved together with theprogress of medical sciences. Particularly the 19 thcentury is related to development of post-mortemexaminations. During that time, Rudolf Virchow(1821-1902) — the creator of cellular pathology— and previously mentioned Karl Rokitansky(1804-1878) exerted great influence on theexamination technique [28].Medical historians also use art for their studies.In the 17 th century, many painters depicteddoctors performing autopsies. The painting byRembrandt “The Anatomy Lesson of Dr JoanDeyman” (1656) depicts a medic performingan autopsy of human brain using a scalpel. Anassistant standing to the right of doctor JoanDeyman holds calvaria, removed (sawn-off) inorder to uncover the brain. We find signs of suchprocedures in anthropological material. Unfortunately,only the middle portion of the paintingremained, while three quarters of it was burnt inthe anatomical theater fire [29, 30].Osteologic data suggest that autopsies were commencedin Poland during late Middle Ages. Theywere not public. Material acquired from historicalcemeteries indicates (we analyzed six archeologicalsites for the purpose of this publication)that sections were carried out earlier than suggestedby written sources. However, developmentof anatomical studies in Poland as well asin other European countries falls on 18 th and 19 thcentury. Possibly, cadavers for the autopsy camefrom cemeteries by the hospitals and churches.First autopsies resulted from scientists’ curiosity,need to search for the cause of the disease anddeath. Didactics played a smaller role.At the turn of Middle Ages and renaissance aswell as in renaissance, people began to realizethe necessity of performing anatomical studiesfor educational purposes. Until 18 th century,public autopsies excited emotions from bothmunicipal and church officials and they usuallyinvolved convicts’ bodies. Cadavers for anatomopathologicautopsies could come from warfare,they could belong to the homeless, prisoners85

© Military Pharmacy and Medicine • 2012 • 4 • 86 – 86or victims of epidemics. However, acquiringcadavers for autopsies without school’s approvalwas not easy.Judicial autopsies were quite superficial. Theywere conducted by surgeons (with guild education)under supervision of medical doctors.Skulls bearing signs of autopsy from the regionReferences:1. Gulczyński J, Iżycka-Świeszewska E, Grzybiak M.Short history of the Autopsy. Part I. From prehistoryto the middle of the 16th century. Pol J Pathol.2009; 3: 109-114.2. Elhadi MA, Kalb S, Perez-Orribo L, Little SA,Spetzler FR, Preul CM. The journey of discoveringskull base anatomy in ancient Egypt and the specialinfluence of Alexandria. Neurosurg Focus. 33 (2);2012: 1-13.3. Debernardi A, Sala E, D’Aliberti G, Talamonti G,Franchini FA, Collice M. Alcmaeon of Croton.Neurosurgery. 2010; 66 (2): 247-252.4. Brzeziński T. Historia medycyny. PZWL;Warszawa 1988.5. Vesalius A. De humani corporis fabrica. Corvina/Magyar Helikon; Budapest 1972.6. Jankowski J. Historia medycyny średniowiecznejw Polsce. Człowiek, populacja, środowisko. PraceDolnośląskiego Centrum Diagnostyki MedycznejDolmed we Wrocławiu. Wrocław 1988.7. Vallentin A. Leonardo da Vinci. Książka i Wiedza;Warszawa 1951.8. Sokół S. Historia chirurgii w Polsce. Cz. 1. Chirurgiaokresu cechowego. Wydawnictwo PAN; Wrocław 1967.9. Seyda B. Dzieje medycyny w zarysie. Tom II. PZWL;Warszawa 1973.10. Paluch A. Ślady występowania zabiegówtrepanacyjnych na ziemiach Polski i Czechosłowacjiw starożytności i średniowieczu. Archeologia Polski.1975; 20: 411-454.11. Paluch A. Trepanacja-zabieg leczniczy i magiczny. Zotchłani wieków. 1971; 37: 37-40.12. Gawlik S. Zagadnienia trepanacji czaszek wpopulacjach pradziejowych z uwzględnieniemtrepanowanej średniowiecznej czaszki z Opola.Maszynopis pracy magisterskiej. Uniwersytet Opolski.Zakład Biologii Komórki, Katedra Biologii Stosowaneji Eksperymentalnej. Promotor: prof. Adam Latała;Opole 2003.13. Talko-Hryncewicz J . O trepanowanych czaszkachXIV-XVI w. z cmentarzyska w Łankiszkach pod Nacząna Litwie. Rozprawy Wydziału Mat-PrzyrodniczegoAU w Krakowie. 1918; LVIII:161-164.14. Jaguś I. Lecznictwo ludowe w Królestwie Polskim naprzełomie XIX i XX wieku. Kieleckie TowarzystwoNaukowe; Kielce 2002.15. O zepsuciach w ogólności czyli z dziejów higieny imedycyny – informator z wystawy. Opole 1997.Review articleof Poland are dated from the 14 th until 19 th century,i.e. from Middle Ages until modern times.Anatomy and its teachings came a long way duringthat time. In the Middle Ages, people stillbased on the teachings of Galen. Beginning withrenaissance, judicial as well as anatomopathologicalautopsies provided increasingly more knowledgeon human physique.16. Kozłowski T. Trepanowane czaszki ze zbiorówZakładu Antropologii UMK w Toruniu. In:Rożnowski F, editor. Biologia populacji ludzkichwspółczesnych i pradziejowych; Słupsk 1992.17. Kapica Z. Człowiek w regionie Brześcia Kujawskiego.Studium archeologiczno-antropologiczne.In: Głębowicz B, editor. Monografia BrześciaKujawskiego; Włocławek 1970.18. 18. Łuczak B, Lorkiewicz W. Świętosławski W.Przypadek sekcji pośmiertnej z cmentarzyskanowożytnego (XIV-XVII w.) w Dąbrównie.Zmienność biologiczna człowieka; 1995; 2:79-83.19. Walewski P, Krzemińska A. Żywi i martwi. Co maczłowiek w środku? Polityka. 2004; 35: 72-74.20. Guszpit P, Kitliński B, Kwiatkowska B, RoczekM. Wyniki ratowniczych badań archeologicznoantropologicznychw związku z remontem i adaptacjąnowej siedziby MPK Sp. Z o. o. przy ul. B. Prusa 75-79we Wrocławiu; Wrocław 2006.21. Słoń M. Szpitale średniowiecznego Wrocławia.Wydawnictwo Neriton; Warszawa 2000.22. Wójtowicz M. Dawne szpitale Wrocławia. MuzeumPrzemysłu i Kolejnictwa; Wrocław 2006.23. Rengachary SS, Colen Ch, Dass K, Guthikonda M.Development of anatomic science in the late middleages: the roles played by Mondino de Liuzzi and Guidoda Vigevano. Neurosurgery, 2009; 65(4):787-794.24. Lyons AS, Petrucelli RJ. Ilustrowana historiamedycyny. Wydawnictwo Penta; Warszawa 1991.25. Mitchell DP, Boston C, Chamberlain TA, ChaplinS, Chauhan V, Evans J, Fowler L, Powers N, WalkerD,Webb H, Witkin A. The study of anatomy inEngland from 1700 to the early 20th century. J. Anat.2011; 219: 91–99.26. Prichard R. Selected Items From the History ofPathology. Am J Pathol. 1979; 97(2): 276.27. Weber CJ. Sekcja zwłok. Podręcznik Shearera. PZWL;Warszawa 2000.28. Skowronek R, Chowaniec Cz. Ewolucja technikisekcyjnej – od Virchowa do Virtopsy®.Arch. Med. Sąd.Krym. 2010; LX: 48-54.29. Cabane P. Rembrandt. Wydawnictwo Imbir;Warszawa 2010.30. Salcman M. The Anatomy Lesson of Dr. Deyman,Rembrandt van Rijn. Neurosurgery. 1995; 36(4):865–866.86 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 87 – 90Radosław Ziemba at al.: Infusion solutions supply in critical …Emergency MedicineInfusion solutions supply in critical circumstances and disastersKatrzyna Parzuchowska 1 , Radosław Ziemba 1 , Jan Hołyński 2 , Adam Ziemba 3 ,Jarosław Hołyński 4 , Ewa Ziemba 51Military Centre for Pharmacy and Medical Technology in Celestynow, Poland2Military Centre for Pharmacy and Medical Technology in Celestynow, Poland3Łódź, Poland4Military Centre for Pharmacy and Medical Technology in Celestynow, Poland5Institute of Psychiatry and Neurology in Warsaw, PolandAuthor’s address:Radosław Ziemba, Military Centre of Pharmacy and Medical Technique, ul. Wojska Polskiego 57,05–430 Celestynów, Poland; e–mail: zx11@op.plReceived: 2012.09.27 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Proper supply of infusion fluids to appropriate destinations during critical situations and catastrophesdepends on meeting the requirements of distribution and logistics. The need for central storageof fluid reserves and subsequent decentralization of medical supplies for immediate casualty managementunder extreme circumstances is directly related to appropriate quantitative and qualitative supply.Effectiveness of emergency rescue services and appropriate medical services depends on gathered fluidreserves, particularly blood products, which should be immediately delivered to the victims of catastropheaccording to their needs. Created norms for the use of infusion fluids during mass events as well astheir distribution should fulfill international standards and criteria developed for the rescue services.Key words: infusion fluids — critical circumstances,disasters.Standards of conduct and practice in criticalcircumstances and during catastrophes developedby appropriate military services and specialemergency rescue services ensure effective supplyof goods based on operating medical equipmentthat proves effective in all conditions. The systemof supply of infusion fluids is based on the normsof consumption of blood replacement and bloodbasedproducts. It should fulfill the fundamentalrequirements for infusion into human circulation.Infusion fluids are administered in order toreplenish the intravascular volume, e.g.: followinga massive hemorrhage in a form of crystalloidsand/or colloids (sterile aqueous solution ofchemical substances devoid of pyrogens, nontoxic,iso – or hyperosmolar to blood plasma).http://military.isl-journals.comInfusion fluids may be divided into crystalloidsor colloids.CrystalloidsCrystalloids are aqueous solutions, inexpensiveto produce, easily available, free of allergens,containing mineral salts: sodium chloride, potassiumchloride, calcium chloride, magnesiumchloride, sodium acetate or sodium lactate inproportions allowing for intravenous infusion inmen. The most frequently used fluids are: normalsaline [0.9% sodium chloride solution], multielectrolytesolution [PWE], Ringer and lactatedRinger solution and a mixture of normal salineand 5% glucose solution [in 2:1 proportion].87

© Military Pharmacy and Medicine • 2012 • 4 • 89 – 90means of storage of strategic reserves for a periodof 3-5 years.The need for constant replenishing infusionfluids during critical situations may not be possibleto accomplish. Therefore, it is strategicallyimportant to fulfill the following criteria:1) The necessity to store infusion fluids –storage decentralization2) Diversification of production and logistics aswell as infusion fluid storage should be thedecision of central crisis management supplyand be available to all subordinate rescueservices.3) Provision of supply fluids is particularlyimportant during mass bodily traumascaused by burns and radiation injuries. ItRadosław Ziemba at al.: Infusion solutions supply in critical …increases to 100% compared with otherinjuries.4) The most important and most relevant forclinical practice infusion fluids are the followingsolutions: dextrans, Ringer, lactatedRinger solutions, colloid solutions.5) Coordination of actions and cooperationwith countries possessing readily availablereserves and/or production lines ready toreplenish storage deficiencies within an integratedlogistics network of NATO membercountries.6) Joint multinational strategic programs andmissions for gaining practical experience,resulting in adequate supply and reactiontime during critical situations and/orcatastrophes.References:1. Hołyński J, Hołyński J: Organizacja zaopatrzeniamedycznego w medycynie ratunkowej i katastrof,Łódź, 2000,T.CCXL.2. Mosiniak T: Medycyna katastrof-system zapatrywaniaw płyny infuzyjne i leki. Biuletyn WAM, 1993; 1.3. Holm C: Resuscitation in shock associated withBurns. Tradition or evidence-based medicine?Resuscitation, 2000; 44(3): 157–64.4. Czermak C I wsp: Burn shock fluid resuscitation andhemodynamic monitoring. Chirurg,2004l 75(6): 599–604.5. Hemington-Gorse SJ: Colloid or crystalloid forresuscitation of major burns. J. Wound Care,2005; 14(6): 256–58.http://military.isl-journals.com89

© Military Pharmacy and Medicine • 2012 • 4 • 91 – 96Łukasz Szarpak: Scope of knowledge regarding administration of oxygen therapy …Scope of knowledge regarding administration ofoxygentherapy among firefighter rescue teams fromVolunteer Fire Departments (OSP)Łukasz SzarpakCollegium Masoviense – College of Health Sciences in Żyrardów, PolandEmergency medicineAuthor’s address:Łukasz Szarpak, Collegium Masoviense–College of Health Science, ul. G. Narutowicza 35, 96-300 Żyrardów,Poland; phone: (+48) 500186225, e–mail: lukasz.szarpak@gmail.comReceived: 2012.07.15 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Introduction. A fire brigade is often the first rescue service at the scene of an accident. Until arrivalof emergency medical services securing casualties, including oxygen supplementation to those whorequire it, remains the responsibility of firefighters.Aim of the study. To evaluate the knowledge regarding administration of oxygen therapy to accidentvictims among firefighter rescue teams.Material and methods. The study was conducted in 2011 and included 100 firefighters working in VolunteerFire Departments in the area of mazovian and lodzkie provinces. We used questionnaires andstatistical methods.Results. Almost 60% of respondents knew when to use the oropharyngeal tube. As much as 61% wereable to indicate that a passive oxygen therapy set is included in a PSP R1 kit. Knowledge on the followingissues was inadequate: time designated to assessment of patient’s respiratory rate (43%), definitionof saturation (30%), causes of unreliable pulse oximetry results (25%), proper adult ventilation volumeusing a self-inflating ambu bag (15).Conclusions. Due to the specific nature of firefighter rescue teams’ work, evaluation of knowledge onprinciples of oxygen therapy is justified, as it may influence patient survival. Knowledge of firefighterrescue teams on patient oxygen supplementation is inadequate.Key words: firefighter, medical response, oxygen, casualty, knowledge.IntroductionFire Department is unquestionably the leadingrescue service in Poland. Authors’ own experienceshows that, in some situations, State orVolunteer Fire Department teams arrive at thescene of the event before medical emergencyresponse teams. We have to realize that everyminute of delay in providing aid, even at abasic level, to the victim reduces the chanceshttp://military.isl-journals.comof recovery [1, 2]. Firefighter rescue teams, dueto the actions they perform, are trained in providingfirst aid. Training programs also includeprinciples of administering oxygen therapyto the patients who need it [3]. Supplementationof oxygen via nasal cannula and assistedbreathing using a self-inflating (resuscitation)ambu bag are only some of the major methods91

© Military Pharmacy and Medicine • 2012 • 4 • 92 – 96of administrating oxygen therapy by firefighterteams.Figure 1: Self-inflating ambu bag with reservoir.Unfortunately, literature lacks scientific reportson the problem of education of firefighter rescueteams on application of oxygen therapy to accidentcasualties. Therefore, it seems importantto conduct research on the level of knowledgeregarding oxygen supplementation among firedepartment rescue teams.Aim of the studyResultsOriginal articleMen predominated among 100 of questionedsubjects. They constituted 85% of cases (n=85).Fifteen percent of respondents were women(n=15; p

© Military Pharmacy and Medicine • 2012 • 4 • 93 – 96Łukasz Szarpak: Scope of knowledge regarding administration of oxygen therapy …with reservoir. Only 35% of respondents pointedto the correct answer – „100%”.Question 2. This question inquired what kind ofoxygen therapy is provided through nasal cannulas.In this case, nearly a half of respondents(46%) gave correct answers by indicating passiveoxygen therapy.Question 3. This question asked respondents topoint to indications for oxygen therapy. Of allrespondents, 32 persons were able to choose correctindications for administration of oxygentherapy to patients during a rescue operation.Figure 4: Answers provided by respondents to question 5.patient” and „ deeply unconscious patient.”The majority of respondents, as much as 59%,answered correctly that oropharyngeal tubeshould be only used in case of deeply unconsciouspatients.Figure 3: . Assessment of knowledge regarding oxygen therapyamong firefighter rescue teamsQuestion 4. In this question respondents weresupposed to answer by what percentage the concentrationof oxygen in the breathing mixtureraises for every 1 l/min of increased oxygen flowthrough nasal cannulas. Only 11% of all respondentsgave correct answers (p

© Military Pharmacy and Medicine • 2012 • 4 • 94 – 96Question 12. In the twelfth question we askedrespondents about the meaning of the term „saturation.”Only 30% of them were able to identifysaturation as blood oxygen concentration. Asmuch as 70% of subjects gave wrong answers.A detailed distribution of answers given byrespondents is depicted in Figure 4.Figure 5: .Answers provided by respondents to question 12.Question 13. This question also referred to assessmentof saturation level. Among the providedanswers („carbon monoxide poisoning,” “cyanidepoisoning,” „hyperthermia”) respondents wereto choose the state, in which saturation measurementwould be unreliable. Only 25% gave a correctanswer, while 75 people responded incorrectly.DiscussionOxygen, an element necessary for human existence,is also used as a drug [4, 5, 6]. Just like inany other case of drug administration, supplementationof oxygen should be given accordingto indications and with careful dosing. For thatpurpose firefighter rescue teams, who are oftenthe ones to administer first aid to victims beforearrival of medical emergency services, undergofirst aid training. First aid course, which lasts66 hours (involving 25 hours of theory and 41hours of practical training), includes issuesrelated to supplementation of oxygen therapy tocasualties [3].Unfortunately, there are no reports in the literatureon the problem of knowledge regardingprinciples of oxygen therapy amongfirefighter rescue teams. Therefore, it is not possibleto compare our results to those obtained byother authors.The level of self-confidence among firefightersfrom the studied group was high and amountedOriginal articleto 4.32 points. There was a great disparitybetween their self-evaluated knowledge and testresults, as evidenced by a 61% rate of incorrectanswers given by respondents. At this point, itis safe to say that members of firefighter rescueteams overstate their knowledge of oxygen therapyadministration.At the scene of rescue operation firefighterrescue teams may administer oxygen therapyto the patient according to first aid procedures.Oxygen therapy may be divided intopassive and active types [7]. In passive therapyoxygen is inhaled due to patient’s preservedventilatory function, while in case of activeoxygen therapy forced ventilation (replacementbreathing) is used [7, 8]. In our material,only 46% of respondents knew the differencebetween methods of passive and active oxygentherapy, as demonstrated by indicating patientventilation via nasal cannulas as an element ofpassive oxygen therapy.Symptoms of hypoxia include: skin cyanosis (ifdeoxygenated hemoglobin concentration fallsbelow 5 g/l) [4, 8]. Moreover, we may observeexcessive respiratory muscle work, which is asign of dyspnea. In case of central nervous systemhypoxia patient may be restless or aggravated.Severe hypoxia may be associated withloss of consciousness. The simplest, non-invasivemethod of evaluating the level of blood oxygensaturation at the site of rescue operation is pulseoximetry. Only 30% of respondents in our studygroup possessed the knowledge that saturation isa measure of oxygen content in arterial blood.Despite pulse oximetry being a routinely usedmethod of saturation measurement, in some situationsthis measurement may be unreliable (erroneous).An example of such situation is carbonmonoxide poisoning. As carbon monoxide hasalmost 250-fold greater affinity to hemoglobinthan oxygen, bonds created as a result of couplingof hemoglobin with carbon monoxide and carboxyhemoglobinformation are extremely strong.It leads to tissue hypoxia. In the above situation,pulse oximeter may show normal values despitethe true level of arterial blood oxygenation beingsignificantly lower. Carbon monoxide poisoningis dangerous, as the most susceptible organs suchas the cardiovascular system and central nervoussystem are damaged first. In severe carbon94 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 95 – 96monoxide poisoning therapy in a hyperbaricchamber is the treatment of choice [9]. Fromour study group, 25% of subjects were familiarwith situations, in which pulse oximetry couldbe unreliable. Due to the possibility of airwayobstruction, manual methods of establishing airwaypatency applied first and followed by instrumentalmethods, firefighter rescue teams shouldpossess the knowledge of oropharyngeal tubeinsertion. Guedel tube is supposed to preventtongue slipping toward the posterior pharyngealwall and causing airway obstruction. A tube thatis either too large or too small may cause obstruction;hence it is important to know how to choosea proper one. Size of the tube should be fittedto each particular patient by placing the tubeagainst patient’s cheek. Tube collar (at the inlet)should be located near the incisors, while its endshould reach mandibular angle. A tube fitted insuch manner ensures airway patency, but dos notŁukasz Szarpak: Scope of knowledge regarding administration of oxygen therapy …prevent from regurgitation – passive movementof stomach contents into the esophagus withouta gag reflex – or from vomiting. Fifty-two percentof respondents knew how to appropriately fitan oropharyngeal tube. A rescue worker shouldremember that oropharyngeal tube should onlybe used in deeply unconscious victims. Most ofthe surveyed firefighters were familiar with thisprinciple, as much as 59% answered correctly.ConclusionsDue to the character of firefighter rescue teams’work, it is justified to examine the knowledgeregarding administration of oxygen therapyamong firefighters, as it may influence patientsurvival.Knowledge of oxygen therapy among firefightersis inadequate.References:1. Szarpak, Ł. ”Zintegrowany system ratownictwaelementem bezpieczeństwa państwa”, [w:] „Katastrofynaturalne i cywilizacyjne. Dylematy współczesnegobezpieczeństwa”, Wyższa Szkoła Oficerska WojskLądowych im. gen. T. Kościuszki, Wrocław 2011,s.127-138.2. Ziemba R. “Criteria of procedures in life-threateningstates”. Military pharmacy and medicine 2012, 5(2):62-68.3. Rozporządzenie Ministra Spraw Wewnętrznych orazMinistra Obrony Narodowej z dnia 23 grudnia 2011r. zmieniające rozporządzenie w sprawie szkoleń wzakresie kwalifikowanej pierwszej pomocy (Dz.U.2011 nr 299 poz. 1778).4. Powrie, K. and S. M. Smith. “Editorial: Emergencyoxygen for adults guideline--a change in oxygentherapy practice?” J.Clin.Nurs. 19.5-6 (2010): 601-02.5. O’Driscoll, R. “A breath of fresh air: a new UKguideline for emergency oxygen therapy.” Br.J.Hosp.Med.(Lond) 69.12 (2008): 670-71.6. Ziemba R (ed): ABC Ratownika – pierwsza pomoc wnagłych, IndexCopernicus, 2011, pp. 55.7. Austin, M. and R. Wood-Baker. “Oxygen therapy inthe pre-hospital setting for acute exacerbations ofchronic obstructive pulmonary disease.” Cochrane.Database.Syst.Rev.3 (2006): CD005534.8. Small, G. and P. Barsby. “How much is enough?Emergency oxygen therapy with COPD.” Emerg.Nurse8.8 (2000): 20-24.9. Van, Meter K. “Hyperbaric Oxygen Therapy as anAdjunct to Pre-hospital Advanced Trauma LifeSupport.” Surg.Technol.Int. XXI (2011): 61-73.http://military.isl-journals.com95

© Military Pharmacy and Medicine • 2012 • 4 • 97 – 104 Review articleEmergency MedicineSustainable development in light of international cooperationRadosław ZiembaMilitary Centre for Pharmacy and Medical Technology in Celestynow, PolandAuthor’s address:Radosław Ziemba, Military Centre of Pharmacy and Medical Technique, ul. Wojska Polskiego 57,05–430 Celestynów, Poland; e–mail: zx11@op.plReceived: 2012.09.19 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Numerous developed countries as well as those entering this path have established strategies of sustainabledevelopment. Areas of activity presented in this work illustrate the wide scope of parameters andchallenges for maintaining sustainable development, both on a local as well as global scale.Key words: hsustainable development, European Union directive, areas of action, eliminating the effectsof environmental pollution, Rio declaration.Balanced development –scope of the conceptSustainable development is defined as a broadlyunderstood social goal, encompassing balancedenvironmental quality accompanied by achievementof social and economical goals. The term“sustainable” may be defined as maintainingenvironmental capacity in time. It also encompassesaspects such as: availability of naturalresources, waste assimilation, cultural values,heritage values, climate stability and maintainingbiodiversity. Such environmental capacitymay be measured using environmental indexessuch as: size of protected areas, size of ecosystems,number of species, level of pollution andsize of resources, particularly with regard to irreplaceablematerials.This term is a result of previously mentionedreport created by the former Norwegian primeminister, current director of World HealthOrganization, Gro Harlem Brundtland, titled“Our common future.” The English term “Sustainabledevelopment” was used there. Finding anhttp://military.isl-journals.comanalogous Polish expression that would properlyreflect the sense of words contained in the mentioneddocument was somewhat troublesome.Following numerous discussions, we translatedthese words as: “trwały i zrównoważony rozwój”(steady and balanced development), althoughthere are some in favor of “ekorozwój” (ecodevelopment)or “trwały rozwój” (steady progress).A concept of “balanced development” as a shorterversion of the previous expression also appearsin various documents and reports. This generalconcept lies at the foundations of environmentalpolitics of many countries. However, somescientific uncertainty and diverse opinions indicate,that there is still a problem concerning thevalue of environmental capacity. However, thereare indexes, which may prove as useful operativeinstruments for comparison with policy goalsand environmental standards, both domesticand international.Strategic environmental evaluation is an instrumentfor comparison of analyzed plans and97

© Military Pharmacy and Medicine • 2012 • 4 • 98 – 104programs with environmental politics and strategieson a national level.Special value of such evaluation is increasinglymore often recognized among European countries.As an example, the goal of European Uniondirective on strategic environmental evaluationwas to ensure proper level of assessment at astage of strategic decisions in all member countries.This project is considered a step towardensuring balanced development and therefore,means of achieving goals of the EuropeanUnion Fifth Environmental Action Program:“Towards Sustainability.”It is an effect of the accepted Rio Declarationon “Environment and Development” and,above all, Agenda 21 on actions undertaken atthe turn of the 20 th and 21 st century in order toensure sustainable development. It is supposedto optimally balance the current status with theassumed, undertaken for the future. Therefore,strategic evaluation is considered an instrumentallowing for inclusion of environmentalaspects and sustainable development intothe mainstream decision-making processesregarding development. As opposed to individualprojects, strategic evaluation methodis directed toward programs at early stages ofplanning. Such approach provides substantialbenefits in terms of strategic evaluation of theprogram at an early stage of its development.Conditions necessary for balancing the developmentgoals (particularly regarding the environment)are analyzed as an element of strategicevaluation.Many developed countries, as well as those enteringthis path, have strategies of sustainable developmentalready behind them in terms of theirplanning as well as describing specific dimensionsof their environmental policies.At a political level, goal descriptions are leastdetailed. Therefore, strategic evaluations areperformed at the same level. They concentratemainly around the analysis of political goals, andtheir environmental cohesion. In the sustainabledevelopment document, it signifies ensuringconsistency with the goals of international andglobal policies expressed through agreements,conventions and other documents.Radosław Ziemba: Sustainable development in light of international cooperationWhy then, are strategic evaluations so important?They include aspects of sustainable growthinto internal decision-making processes. Sustainablegrowth is directed at fulfilling the needs of acontemporary man in such manner that wouldnot prevent the future generations from utilizingenvironmental resources. This requirementresults in the necessity of maintaining balancebetween goals and environmental, economicaland social criteria.Effects analyzed as a part of strategic evaluationmay be divided into four groups:••traditional environmental factors, such asecological effects, quality of water and soil,quality of the air, noise levels, landscape, consequencesfor the population – analyzed withregard to their international, domestic andregional significance;••outcomes associated with imposing balance,which encompass the threat o irreversible,cumulative or secondary effects such as:exploitation of non-renewable resources, lossof biodiversity, valuable natural ecosystems,as well as long-term productivity of forests orrural areas;••induced changes in use of the land, particularlyin relation to urbanization and expansionof municipal peripheries;••political effects of breaching internationalagreements and other domestic policies.Assessment of significance (or importance) ofpredicted effects is a key element of strategicenvironmental assessment process. However, upto date, no index was agreed upon, which wouldmeasure the degree of attained sustainable progress,encompassing various indexes and determininghow a given factor should be weightedagainst other ones. Sustainable balance does notonly determine beneficial effects. They may beunfavorable or, at the least, of little benefit. Allof those effects should be considered through anadvanced grading system, even more so whenvarious factors undergo evaluation. Evaluationcriteria must be established for selected problemsin order to determine the significance of predictedoutcomes.At a strategic level, it is indicated to assess therisk of occurrence of significant outcomes (benefits,losses, conflicts) instead of making prognoses,which in turn should be performed at a98 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 99 – 104 Review articlelevel of evaluation of a particular investment. Forexample, it concerns the risk of effects leading tosecondary enterprises or conflicts with variousdevelopment plans. In this context, the risk ofoccurrence of outcomes derived from secondaryprojects was defined as a product of probabilityof effect occurrence and intensity of this effect.While determining the outcome risk, the followingaspects should be taken into consideration:••environmental absorption capacity orsensitivity;••the scale or extent of the effect, e.g. the degreeto which environmental quality may bedisrupted;••will the effects lead to sustained or temporarychanges?;••domestic or international obligations, goalsand environmental quality standards,••to what degree is reduction of the effectspossible?;••significance of the effect on a national level;••Strategic evaluations allow for inclusion ofenvironmental considerations at a possiblyearliest stage of planning, as in the case ofsocial and economical aspects.Principle no. 4 of the preamble “Environmentand Development” states the following: “In orderto achieve sustainable development, environmentalprotection shall constitute an integralpart of the development process and cannot beconsidered in isolation from it.” Principle no. 8strengthens those ideas, particularly in the fragmentpertaining to the necessity to “reduce andeliminate unsustainable patterns of productionand consumption” by some countries. Economicalinstruments are vital to realization of thosegoals (Principle no. 16), according to the principle:“the polluter should, in principle, bear thecost of pollution, with due regard to the publicinterest and without distorting internationaltrade and investment.”Areas of action forsustainable developmentIn order to face the challenges of the environmentand growth, cosignatory nations decidedon a new form of universal cooperation. Itcompels them to get involved in constant andconstructive international dialogue inspired bythe necessity of establishing more effective andhttp://military.isl-journals.comjust world economy, taking into considerationthe growing co-dependence of societies andthe fact that sustainable development shouldbe a priority for those societies. Conference’s“Documents” state that: “in order to achievethis new cooperation, it is important to avoidconfrontation and create an atmosphere of truecooperation and unity…” (5). In this mission,particular emphasis is put on strengthening ofinternal and international policy and establishingmultidirectional cooperation adjusted tonew conditions.National economical policies and internationaleconomic relations are associated with sustainabledevelopment. It should be noted that, in thisregard, its reactivation and acceleration requiresboth a dynamic international supportive action,as well as decisive national policy. Both of thosefactors should act in parallel. A dynamic andstable world economy based on safe foundationsgives a chance for progress. Therefore,support of international economic circle is adetermining factor.The role of developing countries, free of excessiveexternal debt is noted in this process. Therefore,financial policy must serve it, without restrictionof access to other markets.Data obtained in the 80’s regarding this aspectare fundamentally negative in all cases. Therefore,a change of this state is encouraged. For thatpurpose, an international atmosphere supportivetoward national efforts for growth should be builtup. It is the only requirement for healthy internaleconomic policies of developed and developingcountries toward achieving global progress in thearea of sustainable development.Accordingly, global economy should create anatmosphere promoting achievement of goalsstated in Agenda 21 regarding environmentalprotection and development through:• • promotion of sustainable growth as a result oftrade liberalization;••mutual dependence of trade and environmentalprotection;••ensuring proper funds for developing countriesand taking care of international debts;• • support for macroeconomic enterprisestoward environmental protection anddevelopment.99

© Military Pharmacy and Medicine • 2012 • 4 • 101 – 104 Review articleAnother area of action that could contributeto the safety of long-term progress is the fightagainst poverty. It may be divided into the followingsections:• • providing the poor with sustainable access tothe means of supporting their basic needs;••facilitating integration of sustainable accessto the means of support with environmentalprotection.Changing the consumption model, which is abroad topic and its problems are mentioned innumerous chapters of Agenda 21, serves thoseareas. They are primarily located in the chaptersrelated to the use of energy, transport, wasteas well as economic instruments and transferof technologies. The areas of action include thefollowing:• • balancing the models of consumption andproduction,••undertaking appropriate policies and economicstrategies by individual countries inorder to eliminate the imbalanced consumptionmodels. The goals of the former areainclude the following:••promoting a model of consumption and production,which would not lead to ecologicaldamage and fulfill the needs of humanity,••achieving better understanding of the roleof consumption in the process of sustainabledevelopment as well as introduction of morebalanced consumption models.Poverty and degradation of natural environmentare closely related. If poverty leads to ecologicalcrises, the majority of cases of sustained environmentaldegradation result from an imbalancedmodel of production and consumption. Therefore,in the coming years, governments togetherwith appropriate supporting organizationsshould strive to achieve broad goals, including:• • promotion of effective production processesand balanced consumption in the process ofeconomic growth, taking into considerationthe needs of the developing countries,••developing strategies of internal actions,which will allow for introduction of balancedproduction and consumption models,••strengthening the factors that support aproduction – consumption model consistentwith sustainable development and promotionof actions for transfer of environment-friendlytechnologies to developing countries.http://military.isl-journals.comThese goals pertain to the latter area of action.In several chapters, areas of action are directlyconformed to the security issues:••environment-safe application of biotechnology(16),••environment-safe utilization of toxic anddangerous chemicals, fighting illegal tradingof those chemicals (19),••environment-safe management of dangerouswaste••preventing illegal trade of dangerous materials(20),••environment-safe management of solid wasteand residues from wastewater treatment plans(21),••safe and environmentally friendly managementof radioactive waste (22),Biotechnology, as a combination of genetic engineering,biochemistry and microbiology, is anarea of intensely developing science, constitutinga compilation of methods of genetic engineering.Not all fundamental environmental problemsmay be solved using biotechnological processesto attain sustainable growth. The reality mustdiminish the expectations. However, biotechnologistsannounce expectations of great contributionsto, e.g. progress in health care, increase infood safety by introducing methods of sustainedand ecologically sustainable agriculture as wellas detoxication of dangerous waste. It should beaccompanied by general partnership betweencountries with rich biological resources, but lackingthe experience and investment funds necessaryfor utilization of those resources throughbiotechnological processes and countries withbiotechnological experience. This experiencerefers to the scope of transformation of biologicalresources in a manner, which would allowthem to contribute to sustainable development.Described areas of action promote the principlesof creating environmentally healthy uses forbiotechnology agreed upon by the internationalcommunity, in order to raise public confidenceand convince the community to support ecologicallysafe uses of biotechnology.General policy indicates, that chemicals can beused to meet the economic and social needs ofpeople around the world in a rational and largelysafe manner. However, there is still a lot to do toensure environmentally safe conduct with toxic101

© Military Pharmacy and Medicine • 2012 • 4 • 102 – 104chemical substances. Two main problems arise inthis area, particularly when it comes to developingcountries:• • absence of sufficient scientific informationallowing for assessment of risk associated withuse of large numbers of chemical substances;••lack of means for assessment of chemicalsubstances owned and used by people.The processes of severe chemical environmentalpollution take place in various industrial centersaround the world in the recent years. It is associatedwith threat to human health, genetic structureand reproduction, as well as to the environment.Elimination of the effects of contaminationrequires large expenditures and development ofnew technologies. Long-term effects of chemicalenvironmental contamination leading to climaticchanges were only recently recognized andunderstood. Also recently, the humanity realizedthe extent of those effects. A large number ofinternational institutions are involved in worksconcerning chemical safety. Programs for itspromotion were implemented in many countries.These works have international implications, asdangerous effects of chemicals know no nationalboundaries. However, significant aid for nationaland international enterprises in this area is necessaryin order to work out methods of environmentallysafe use of chemical substances.Seven areas of action are proposed in this area:• • broadening and acceleration of internationalevaluations of chemical threats,••unification of classification and labeling ofchemicals,••exchange of information regarding toxicchemicals and chemical threats,••establishing programs for risk reduction,••strengthening national capabilities and skillsfor effective toxic substance management,••preventing illegal international trade of toxicand dangerous substances,••deepening international cooperation in someareas of actions.Effective control of production, storage, handling,recycling, transport, retrieval of raw materialsand management of dangerous wastes areimportant for human wellbeing, environmentalprotection, as well as management of naturalresources and sustainable development. Preventingformation of dangerous materials requiresRadosław Ziemba: Sustainable development in light of international cooperationknowledge, experienced staff, resources andfinancial means, as well as technological and scientificpotential. International trade of dangerouswastes, with partial breaching of nationallegislation and international policies, causingharm to the environment and public health in allcountries, particularly the developing ones, is amatter of concern for the international society.The master task in terms of management of vitalprocesses involves the greatest possible minimizationof dangerous waste production, as well assuch management of waste products so that theywould not cause harm to health and the environment.It encompasses four areas of action:• • promoting prevention of dangerous wasteformation and minimization of the amountsof those products,••promoting and strengthening internationalcooperation in management of cross-bordermovement of dangerous wastes,••promoting and strengthening institutionalpowers with regard to dangerous wastemanagement,••preventing illegal international trade of dangerouswaste products.The General Assembly concurred that environmentallysafe waste management is one ofthe main actions undertaken in order to maintainthe wellbeing of global environment and toattain environmentally healthy, stable growth ofall countries.Areas of action described in this chapter ofAgenda 21 are closely related to the followingareas of action contained in other chapters:• • quality protection and use of inland watersupplies (ch. 18);••promoting sustainable development of humanhabitats (ch. 7);••protection and promotion of human health(ch. 6);••changing the model of consumption (ch. 4).According to this, the extent of necessary actionsshould be based on a hierarchy of goals and concentrateon four main fields of action related towaste products. They are mutually interconnectedand supportive of each other. They comedown to:••minimizing the amount of waste;102 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 103 – 104 Review article••maximization of environmentally safe use ofsecondary materials and waste recycling;••promotion of environmentally safe eliminationand processing of waste products;••broadening the scope of services with respectto elimination and processing of wasteproducts.Radioactive waste is formed both during use ofnuclear fuel as well as radioactive materials (inmedicine, science and industry) Radiological riskand safety threats are diverse on the part of radiologicalwaste: they range from very small to great.Safe and environmentally harmless managementof radioactive materials, including their minimization,transport and utilization is of great importance.Most countries with leading nuclear energyprograms have undertaken administrative andtechnological systems of waste management. Inmany other countries, still preparing for nuclearprograms or only using radioactive materials,there is still a need for creation of such systems,which is becoming increasingly urgent.A fundamental goal of such program is to ensuresafe management, transport, storage and utilizationof radioactive wastes. It is directed at protectionof human and environmental health and iscontained within a broader framework of interactiveand integrated approach toward their managementwithin a broadly understood safety system.The described areas of action illustrate the extentof parameters and challenges for maintainingsustainable development.References:1. Janikowski R., Wielokrotny model decyzyjny, jakonarzędzie oceny oddziaływania projektowanejdziałalności człowieka na środowisko. JETU,Katowice, 1993.2. Jendrośka J. Rządowy projekt ustawy o postępowaniuw sprawie ocen oddziaływania na środowisko oraz odostępie do informacji o środowisku i jego ochronie,(w:), Problemy ocen środowiskowych, kwartalnik Nr1(8), 2000.3. Kozłowski S., Koncepcja ekorozwoju jako podstawapolityki ekologicznej państwa.(w:) B.Poskrobko(red.), Działalność gospodarcza a ochronaśrodowiska przyrodniczego, Biuro Badań i WdrożeńEkologicznych, Białystok 1992.4. Kozłowski S., W drodze do ekorozwoju, PWN,Warszawa, 1997.5. Patrz: Dokumenty końcowe Konferencji NarodówZjednoczonych..., cyt. wyd., słowo wstępne.http://military.isl-journals.com103

© Military Pharmacy and Medicine • 2012 • 4 • 105 – 110Łukasz Szarpak: Selected aspects of communication between emergency services …Emergency medicineSelected aspects of communication between emergency servicesand the mass media in crisis situationsŁukasz Szarpak, Marcin MadziałaCollegium Masoviense – College of Health Sciences in Żyrardów, PolandAuthor’s address:Łukasz Szarpak, Collegium Masoviense – College of Health Science, ul. G. Narutowicza 35, 96-300 Żyrardów,Poland; phone: (+48) 500 186 225, e–mail: lukasz.szarpak@gmail.comReceived: 2012.07.18 • Accepted: 2012.09.11 • Published: 2012.09.28Summary:We live in times where information is the supreme value. The mass media seek sensation and oftenmisinterpret the situation, which usually occurs in the case of limited access to information. Due totheir mediagenic nature, crisis situations as well as emergency actions taken to eliminate their consequencesare undoubtedly a treat for journalists. Correctly performed rescue operations are essentialduring events that make people suffer or feel endangered. Nonetheless, appropriate conveying informationabout performed actions to the media, and then to the society, is a crucial element of rescue operationsand influences both perception of emergency services and prevention from spreading speculationand panic in the society.Key words: media, crisis situation, rescue operation, emergency services, panic.IntroductionContinuous civilization development and growingpopulation make us live in expandingagglomerations, which results in the fact thatthe issue of disasters is becoming increasinglyimportant. Phenomena bearing marks of crisis,although varied and reaching different extents,which makes it difficult to define them precisely,have some common features [1-3]. Firstly, in viewof the fact that nobody can expect crisis situationsat a particular time and in a particular place, theaffected population is usually helpless. Secondly,the extent of damage and number of people inneed exceed the ability to satisfy all expectations.Another feature of crisis situations is their mediagenicnature [2,3].For hundreds of years, since humans startedto deal with disastrous events, the concept ofhttp://military.isl-journals.comcatastrophe has evolved. At present, there arenumerous definitions of “catastrophe”[4]. Themost accurate one, with regard to the way ofthinking in any situation that surpasses in extentthe abilities of rescuers and bears the features ofcatastrophe, is a definition approved in the USAby the Federal Emergency Management Agency(FEMA) [5]. It defines catastrophe as an eventcausing death, injuries or damage to possessions,to an extent that makes routine emergencyactions insufficient. According to this definition,catastrophe occurs suddenly and requires immediate,coordinated actions taken by many individualsand institutions.Efficient crisis management is not only a medicalemergency assistance provided to casualties.One of the basic conditions of effective105

© Military Pharmacy and Medicine • 2012 • 4 • 106 – 110actions reducing the consequences of the eventis a well-organised communication betweenemergency services units, including the fire brigade,the police, the medical rescue, etc., as wellas between emergency services and the public.Due to technical advancements it is possible toexchange information via the electronic media,however, the basic way of contact between theemergency services, the authorities and the societyis undoubtedly public media, including press,radio and television stations (TV and radio areelectronic media) [3,6].Communication with the media in crisis situationsmay be divided into three stages. The firstof them includes actions preceding a crisis situation,and next two stages – actions during andafter eliminating such a situation [1,2,6,7].Actions preceding catastrophesCommunication infrastructure, consolidating allemergency services and the public, is an inherentelement of the efficient security system. Theabove mentioned mass media, i.e. radio, television,press, and nowadays also the Internet, aremain channels of conveying information. Lackof proper circulation of information between theemergency services leads to chaos, whereas, disturbedcommunication with the media results inmisinterpretation of the event, which may raisemany unfavourable interactions in the public,including panic.Actions preceding a crisis situation are inherentpreparatory stages for various emergencyservices and crisis panels. Continuous updatingof knowledge by people who coordinate actionsof emergency and crisis services, results in progressingimprovement of professional skills [8,9].Constant training, exercises and simulationshelp these services, to a greater or lesser extent,prepare for possible crisis scenarios.Exercises should not only involve rescue services,but they should also include elements of cooperationwith media [7,10]. In the future it willhelp avoid information chaos. It is important tobecome acquainted with the rules of the publicmedia. It is also worth establishing and practisingthe method of appointing persons responsiblefor contacts with the media (spokespersons),creating healthy relationship with the media andReview articlepreparing (adequately to the situation) necessaryinformation for the public. Therefore, establishingprocedures for crisis situations seemsindispensable.Media communicationand legal provisionsCirculation of information between public servicesand media is regulated by legal acts, ethicalcodes and internal regulations. Thereby, suchregulations impose duties on the emergencyservices workers, authorities and journalists.Informing the public about states of danger isdefined by, among others, a notation in the UNUniversal Declaration of Human Rights of 1984[11]. In the face of a crisis situation, people wouldfeel much safer to know that they receive reliableinformation about current actions and changesthat may affect their lives and environment.Act of 26 January 1984 – Press Law, conferredpowers on journalists to obtain informationabout actions of government agencies, publiccompanies and other organisational units,whereas, heads of such units, spokespersons orother persons authorized to convey informationto media are responsible for providing suchinformation [12]. However, according to theabove Act, journalists should make every effortto be careful, reliable and honest while collectingand conveying press materials; they shouldcheck credibility of all obtained informationand publish its sources. According to the Act,the media are obliged to publish (free of charge)statements issued on the basis of acts, announcements,ordinances or resolutions of the centraladministration authorities and governmentadministration authorities in the province, and,what is important for this paper, they are obligedto publish (free of charge) announcements issuedby the government administration authoritiesor local governments and concerning crisis situationsdefined in the Act on crisis managementof 2007 [13].Legal provisions concerning reliable conveyinginformation about events and phenomena in thecountry and abroad, are also included in the Acton the state of natural disaster [14] or in the Acton National Broadcasting Council. Principlesof correct collection of and publication of pressmaterials may be found not only in the above acts106 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 107 – 110but also in ethical codes, including the PolishCode of Ethics for Public Relations Associationand the Ethical Code of Journalists.A great example of internal acts referring to therole of communication between the emergency(rescue) services and the media may be internalregulations of the National Fire Service of 1998,defining press-information activity within theNFS structures, including the actions of spokespersonsand cooperation between NFS andjournalists during crisis situations. In 2004, theHeadquarters of the National Fire Service establishedprinciples of proper conduct for the commandingofficer during a rescue operation. Theabove-mentioned guidelines categorically forbidthe commanding officer to inform the mediain the event place about the reasons, identitydata and names of casualties. Guidelines alsoclearly define the way of taking over informationalfunction by a person appointed to a postof a spokesperson.Appointment of spokespersonsŁukasz Szarpak: Selected aspects of communication between emergency services …media about progression of rescue actions fromthe onset of crisis. Such a person should be chosenmuch earlier and systematically prepared forhis/her role, since in order to increase the level ofreliability of the released statement, the speakermust show competence, enjoy respect, be reliableand dynamic, and enjoy a positive opinion. Sucha person should have several crucial abilities:••must be resistant to stress and control his/herown emotions;••must have extensive substantive knowledgeabout activities of the emergency servicesand know the services which he/she is talkingabout;••must have great interpersonal abilities andmake contact easily.Professional actions of a spokesperson build uptrust of the media in emergency services andstrengthen positive public opinion about theirhard work [16]. Thus, it is so important to obeythe rules defining what a spokesperson should orshould not do.A deficit of information is commonly associatedwith crisis situations. From a point ofview of the media, a crisis situation is a specialopportunity to develop their own image amongmedia market participants while gaining asmuch information as possible and reporting itto the public [15] . In order to avoid informationchaos, it is important to take actions whichguarantee that statements issued by all personsauthorised to convey information are consistent,relevant and answer the questions insteadof ignoring them using a phrase “no comments”.A requirement of consistent communication isone of the most important elements connectedwith the entire management of communicationin crisis situations. Consistency is necessaryfor information exchange between particularemergency services, organizations and themedia. Therefore, it seems important to developa strategy of communication with both internal(services) and external (media and publicopinion) environment.Misinterpretation of the event is a commonaction taken by the media, which results fromshortage of information or conflicting datapresented to the public. Thus, it is essential toappoint a person who will solely inform thehttp://military.isl-journals.comTable 1: Principles of spokesperson’s work.AllowedRelease information onlyvia a press spokespersonresponsible for public relations.Not allowedSpeculate on:••possible causes of thecrisis situation;••number of fatalities;••further scenarios of events;••date of termination of theactions.Provide information thatCreate equal opportunities to can hinder the progress ofobtain information by various rescue operations, raisetypes of media.panic or bring about any newthreat.Release only proven informationSupervise information outflowby:••own, frequent contacts withthe media;••collecting all information ina version reported by themedia to the public;••controlling movement ofjournalists in the endangeredarea.Issue official statements toincompetent personsEvaluate rescue operationswhen they are in progress.Lay the blame for the situationon anyone.Misinform the media.107

© Military Pharmacy and Medicine • 2012 • 4 • 108 – 110Preparation of informationDuring a rescue operation, a lot of informationasked by the media is unpredictable. However,there is still considerable amount of informationthat can be prepared earlier and successivelyreleased to the public. Such information includes:••alarm information;••instructions for behaviour in crisis situations,••data concerning places and sources of informationand help;••data concerning services involved in therescue operation;••appeal to support services in relevantsituations.When preparing rules for cooperation with themedia, all forms of communication should betaken into consideration [10,17]. The most popularforms of communication in crisis situationsinclude: press note, statement, information, telephoneresponse, written response, interview,talk, utterance and press conference.Actions during a crisis situationCommunication with the media during rescueoperations mainly includes: appointment of a24-h duty spokesperson, collection of informationfrom various services, preparation andconveying information to journalists, informationmanagement for the regional and nationalmedia, checking and correction of informationthat was released to the media, organisation ofpress conferences, responding and release ofstatements on the current situation, and coordinationof journalists work in the area involved inrescue operations.It is important to establish an information centrenear the place of rescue actions [3,4,9]. Personsresponsible for contact with the mediashould all the time monitor the situation andrespond immediately to the needs reported bythe media, if it is possible and not against the rescueoperation.Another important element regarding participationof the media in a crisis situation is to separateand adapt for journalists the area aroundthe event site. This area is separated accordingto two important principles. The first of them isReview articlethe superiority of rescue operations interest. Thisprinciple forbids the media to enter places, whereit could pose a risk to the rescue action or to themedia. The second principle, used while separatingareas for the media during catastrophe, isthe best possible availability of the media. Themedia should have possibly the best, acceptable“viewpoint” for observation of the rescue actions,to assure that when looking for a good place fortaking pictures the media will not hinder actionstaken by emergency services.Persons responsible for contacts with the mediaare obliged to separate such areas, in agreementwith persons in charge of the rescue operation.Actions after eliminatinga crisis situationAfter termination of the rescue actions, personsresponsible for contacts with the media areobliged to inform the local community about thecurrent situation and taken precautions, and toinform the entire country about a situation in theparticular region.Unfortunately, it is often seen that the end of therescue operation is the end of all actions aimed toeliminate a crisis situation. However, it should bean introduction to preparations connected withfuture actions. Conclusions should be drawnfrom all experiences, regardless of whether theywere positive or negative; all actions should alsobe thoroughly analysed. Efforts put into analysingthe particular action should help revisearrangements and prepare for future events.SummaryWhen analysing this paper, it may be hypothesizedthat the public authorities, emergency servicesand mass media are all responsible for reliableconveying the current information in crisissituations.However, cooperation with the media is not easy.Journalists are characterised by natural scepticism.They are more interested in criticising theservices and government authorities responsiblefor controlling the crisis situation than in defendingor justifying such services and authorities.Probability of negative comments given by themedia during a crisis situation is almost 100%.108 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 109 – 110Although several acts, including the Act on thestate of natural disaster and crisis management,imposed on the media an obligation to reportany threat (in agreement with the local authorities),we should remember about the role of theway how information reaches editorial offices.Thus, it is important to work out methods ofŁukasz Szarpak: Selected aspects of communication between emergency services …presentation to the media a problem of catastropheor emergency.Taking the above-mentioned actions increasesthe chances for peaceable, and at the sametime, effective participation of journalists in acrisis situation.References:1. Beaudoin, C. E. “Assessment of a media campaign andrelated crisis help line following Hurricane Katrina.”Public Health Rep. 123.5 (2008): 646-51.2. Arnold, J. L. “Disaster myths and hurricane Katrina2005: can public officials and the media learn toprovide responsible crisis communication duringdisasters?” Prehosp.Disaster.Med. 21.1 (2006): 1-3.3. Ng, K. H. and M. L. Lean. “The fukushima nuclearcrisis reemphasizes the need for improved riskcommunication and better use of social media.”Health Phys. 103.3 (2012): 307-10.4. Barr, P. “Staying connected. Social media put to workwhen disaster strikes.” Mod.Healthc. 41.36 (2011): 33.5. Keim, M. E. and E. Noji. “Emergent use of socialmedia: a new age of opportunity for disasterresilience.” Am.J.Disaster.Med. 6.1 (2011): 47-54.6. Schlecker, M. and E. Hirsch. “Incomplete knowledge:ethnography and the crisis of context in studies ofmedia, science and technology.” Hist Human Sci. 14.1(2001): 69-87.7. McLearn, D. “FDA crisis management and the media.”PDA.J.Pharm.Sci.Technol. 50.3 (1996): 144-46.8. Misterska, E., M. Glowacki, and Z. Wlodarczyk.“Mass-media and the transplantation crisis: theexample of Poland.” Med.Sci.Monit. 16.8 (2010):RA171-RA176.9. Petriuk, V. A. and E. I. Pokrovskaia. “[Role of the massmedia in eradication of the consequences of a naturaldisaster in summer 2002 in Karachai-ChercassianRepublic].” Zh.Mikrobiol.Epidemiol.Immunobiol.6(2003): 124-26.10. Rich, E. “’I see her being obesed!’: Public pedagogy,reality media and the obesity crisis.” Health (London)15.1 (2011): 3-21.11. Uchwała Senatu Rzeczypospolitej Polskiej z dnia10 grudnia 1997 r. w sprawie obchodów 50 rocznicyuchwalenia Powszechnej Deklaracji Praw Człowieka(M.P. 1997 nr 85 poz. 851).12. Ustawa z dnia 26 stycznia 1984 r. Prawo prasowe(Dz.U. 1984 nr 5 poz. 24).13. Ustawa z dnia 26 kwietnia 2007 r. o zarządzaniukryzysowym (Dz.U. 2007 nr 89 poz. 590).14. Ustawa z dnia 18 kwietnia 2002 r. o stanie klęskiżywiołowej (Dz.U. 2002 nr 62 poz. 558).15. Stokstad, E. “Gulf oil disaster. Hunting for plumes,learning to live in a media spotlight.” Science 329.5987(2010): 22-23.16. Saxena, D. B., H. M. Shah, and P. Mishra. “Mediaresponse to disaster.” Indian J.Med.Sci. 63.1 (2009):28-29.17. Spence, P. R., et al. “Media use and information needsof the disabled during a natural disaster.” J.HealthCare Poor Underserved 18.2 (2007): 394-404..http://military.isl-journals.com109

© Military Pharmacy and Medicine • 2012 • 4 • 111 – 118Magdalena Cybulska at al.: Anthropological and archeological sources …History of medicineAnthropological and archeological sourcesin medical historian’s studiesMagdalena Cybulska, Agnieszka Adamczyk, Agnieszka Młudzik, Czesław JesmanHistory of Science and Military Medicine Department, Medical University of Lodz, PolandAuthor’s address:Magdalena Cybulska, History of Science and Military Medicine Department, Medical University of Lodz,ul. Żeligowskiego 7/9, 90-643 Łódź, Poland; phone: (+48) 426393270, e–mail: magdalena.cybulska@umed.lodz.plReceived: 2012.10.21 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:Medical historians most often refer to written sources in their studies on the matters of health andsickness over the centuries, but also take advantage of the materials acquired through excavations – inother words anthropological and archeological sources. Skeletal material may exhibit signs of sickness,traumatic injuries, therapeutic procedures such as trepanations or amputations, as well as proceduresemphasizing one’s social status in a society (e.g. skull deformities). Various items for use in medicalprocedures may be found during excavations. Archeobotanical material contains remnants of medicalplants. Immovable sources: remnants of medieval hospitals or baths also point to the means of treatmentutilized by given populations. Anthropological and archeological sources are often difficult tointerpret. The description of medicine on Polish territories made on their basis is certainly fragmentary.Despite that, anthropological and archeological data are important sources of knowledge for a medicalhistorian, as they allow investigation into human past all the way to the times when written sources werenot available.Key words: history of medicine, anthropology, archeology, skull trepanations, historical sources.There are many multidisciplinary publicationsappearing in the current scientific literature.Many scientists representing various fields compilea common research project. In their work,medical historians also avail from various fieldsof knowledge, utilize research methodology notonly from the area of history, but also ethnography,archeology and anthropology. Each historicalwork must be based on sources. In literature,we may find several definitions of a “historicalsource.” According to a definition published bya historian, Jerzy Topolski, “the source” encompassesall information (in an information theorysense) on social history regardless where theycome from, including the mode of informationtransmission (information channel) [1]. Based onhttp://military.isl-journals.comthe sources, one may attempt to reconstruct thelives of people in the past. Studies on the past,such as history and archeology are mutuallycomplementary and overlapping.In this publication we took interest in archeologicaland anthropological sources utilized by medicalhistorians in their work. In our deliberations,we focused on the material obtained in Poland.The outline of periodization from neolithic tomedieval times mentioned in our work also concernedPolish territories [2].Archeological sources are material signs ofhuman activity extracted from the earth or water(acquired through archeological methods). They111

© Military Pharmacy and Medicine • 2012 • 4 • 112 – 118allow for reconstruction of various fields of life.During excavations we find items, which couldhave served during medical or hygienic procedures.Not many archeologists are concernedwith medical or surgical instruments from prehistoricaland medieval times. Hygienic items:knives, razors, pincers, and mirrors are morebroadly described. There are numerous publicationsin foreign literature discussing surgical andmedical instruments from the Roman periodof Iron Age (since the 1st century A.D. untilabout 375 or the end of Roman Empire) foundby the archeologists within the region of RomanEmpire.Anthropological sources (bone material) allowfor observing pathological changes (injuries, illness)and traces of intentional procedures performedby the first “surgeons.” Paleoanthropologyis concerned with morphological analysis ofhuman skeletal remains. The goal of those studiesis to determine important biological features (sex,age, height, body mass) of individual and entiregroups of people. Paleopathology is concernedwith disease lesions, developmental changesand traumatic injuries visible on excavated skeletalmaterial. It should be noted that this field ofknowledge is at the border of paleoanthropologyand medicine. We are mainly interested in thestructure of health in a given population [3].Very little room is devoted in Polish scientificliterature to prehistoric medicine. It is probablya result of scarce sources and difficult access tothem. There are publications concerning developmentof medicine in the Middle Ages. Here, wecan already encounter written sources: chronicles,annals and letters. They provide informationon the first Polish physicians, famines and epidemicsthat tormented the contemporary society.Authors of numerous publications [4,5,6] pointedto the need for further studies on history of medicinebased on anthropological sources. Findingthe signs of diseases besetting people ages ago inskeletal material or soft tissues may help us understandpathological phenomena occurring in thebody, as many diseases have been known sinceneolithic era (since about 5400 until 2200 /2100B.C.). Going back in time allows for noting diseasesymptoms and investigating the mode oftransmission of some diseases, particularly theones causing epidemics, with groups of people.Review articleImmunological changes occurring in a human asa result of civilization progress as well as environmentaland social changes constitute anothercurious phenomenon. In prehistorical times, onlybiologically strong individuals reached adult age.Mortality of women in childbearing age was highand mean lifespan was shorter for women thanfor men. Today the situation became reversed, aswe know from demographic studies [7].Among the Slavs, as in case of other nations,medicine probably grew from everyday experiences,beliefs and customs. The cause of the diseasewas seen in natural factors such as: poornutrition, dirtiness, infections, as well as supernaturalfactors: witchcraft and enchantments.According to the beliefs of ancient Slavs, deitieswere also responsible for health or sickness [8].Archeological sources on medicine are scarce.First of all, we would like to understand how, withwhat and where people were treated. The mostarcheological sources, on which we may base ourdeliberations, come from early Iron Age (fromthe beginning of 1st century B.C. until about4 th century B.C.) and the Middle Ages (from 7 thcentury until half of 16th century). Here, we canmention immobile sources: remnants of medievalhospitals and baths, as well as mobile ones: medicalinstruments, medicine containers (e.g. madefrom antlers), pharmaceutical containers. Fromthe earliest times, people attributed therapeuticproperties to various talismans made of bone,stone or fossils. Belemnites – fossilized molluskshells (cephalopods), also called “lightningarrows”, were particularly valuable. They wereapplied to the affected areas, but also ground topowder and given to drink. Belemnites were usedfor treatment of: rheumatism, colic, eye diseasesand during childbirth; they also protected frombewitchment [9]. Use of talismans was popular infolk medicine. Animal horns and bones, as wellas roots of particular plant species were most frequentlyused as materials.Archeobotanical studies of plant fossils provideinformation on plants present in humanenvironment, including edible ones, grownor derived from natural positions. Among thearcheobotanical material, we may also distinguishtherapeutic plants. Plants used in medicinecould be grown in home gardens or gatherednear human settlements, cities or villages.112 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 113 – 118Magdalena Cybulska at al.: Anthropological and archeological sources …According to the data from archeological excavationsites in the area of Poland, the followingplants were used in medicine: poppy (hypnoticand sedative properties), Lithospermum officinale(antidiabetic properties, treatment of hypertension,hyperthyroidism, contraception), Sambucusnigra (diuretic, diaphoretic, antipyreticactions), Agrimonia eupatoria (antidiarrheal,antirheumatic, antihemorrhagic properties),Valeriana officinalis (sedative, hypnotic), Filipendulaulmaria (antipyretic, diaphoretic, diureticand antirheumatic properties), Hyoscamus niger(anesthetic, analgesic, hallucinogenic properties)[10, 11, 12]. Many plants such as: red raspberry,black raspberry, blackthorn, wild strawberry,bog blueberry or cranberry, were acquired fromnatural habitats for consumption since prehistoricaltimes. They were processed and turnedinto juices. They were rich sources of vitaminsfor contemporary people. Oil plants (commonflax, hemp, opium poppy) could be also used fortherapeutic purposes. Plant leafs (common hazel,broadleaf plantain), sprouts (common yarrow),flowers (mead wort, common elder), rootstalks(gromwell), roots (valerian, common chicory)and fruits (common elder) were used. Peppermintor cumin, spices used in medieval times,also had therapeutic properties. Use of some ofthese plants was continued in folk medicine andthey are still utilized in modern medicine, thustheir application had reasonable grounds. In folkmedicine, some of them (opium poppy, commonSt. John’s wort, Sambucus nigra) were ascribedmagical properties.The issue of medical instruments used fromprehistoric times until Middle Ages is difficultto describe. On the basis of discovered archeologicalitems we think, that stone or flint instruments(scrapers, recloirs, chipped stones), as wellas tools made of organic materials such as boneand antler blades were used in skull trepanationsin the neolithic era. In the following eras, peoplestarted making medical tools out of bronzeand iron. With the evolution of other tools camethe evolution of surgical instruments, althoughaccording to our knowledge, they derive fromcraft tools [13]. We possess the most informationon medical tools from the following periods: LaTene (from 400 B.C. until the beginning of 1stcentury A.D.) and Roman period (from the beginningof 1st century A.D. until about 375). Thereare many publications in archeological literaturehttp://military.isl-journals.comon surgical and medical instruments from theperiod of roman influences, while descriptionsof La Tene period are significantly scarcer. Therefore,we find it easier to classify antique medicalinstruments gathered in museum collectionscoming from those two periods. However, thereare few classified medical tools from La Tene orRoman periods coming from Poland. Certainly,Polish museums may contain these kinds ofitems, which were not correctly identified. Allmedical tools dated to the La Tene or Romanperiods were found in southern Poland, mostlyin the Silesian region. In prehistoric times, Silesiawas an area under Celtic expansion. The AmberRoute ran through this region, along which wefound numerous antiques from Rome and itsprovinces. Mercantile expeditions from SouthernEurope traveled this road to the southern BalticSea and further, toward the northeast [14]. Overthe centuries people probably used tools meantfor other purposes, such as food preparation,hunting, leather dressing and magical or ritualacts to perform medical activities and minor surgicalprocedures. Medical tools from La Tene andsubsequent Roman periods were decorated (withengravings, notches and ornaments) indicatingthat, despite the rational foundations of interventionalmedicine, it was still influenced by magicand rituals. Esthetic appearance of surgical toolswas supposed to inspire patient’s confidence. Theart of decorating gradually progressed throughthe ages. Shapes of medical instruments fromthe Iron Age often resemble the 19th centuryor modern tools. A knife from La Tene period –“trephine,” with a semicircular working surface,resembles the 19 th century trepanation knivesillustrated in contemporary medical books [15].Trepanation drills from 16 th century driven bya chord tied around the working part resemble“modiolus,” used for the same purpose in theRoman period. Current surgical instrumentationincludes types of tools similar to those fromthe Roman period such as: exploration probes,scalpels, catheters and specula. During the IronAge we may note progress in the field of medicalinstruments. Roman medical tools are morediverse and more precise than those made in theLa Tene period.Like in the modern era, disease morbiditydepended on host factors (given organism), itsgenetic makeup, environmental factors andfeatures associated with particular pathogens.113

© Military Pharmacy and Medicine • 2012 • 4 • 114 – 118Disorders observed on osteological material maybe divided into several groups: injuries, specificand non-specific inflammatory diseases, degenerativechanges, systemic diseases, tumors andtumor-like lesions, developmental changes, masticationorgan disorders. Improper diet, vitamindeficiency as well as periods of starvation andparasitic diseases leave traces on the bones (particularlyin young individuals, whose bones arestill growing). Here, we can mention changesin the orbital floor, cribra orbitalia, frequentlyobserved since the Neolithic Age, rickets – alsooccurring since Neolithic era, although less frequent,enamel hypoplasia or scurvy. Childrensuffering from the above disorders certainly hadlesser chances of surviving to adult age.Degenerative and deforming, age-related (olderage category) and work-related (overload) lesionsare also often frequently observed on the skeletons.Such changes are particularly common inthe Medieval Age. It may also be related to gradualprolongation of human lifespan. There arelesions seen on vertebrae, including osteophytes,flattening of vertebral bodies, Schmorl nodules,and deformations of articular surfaces. Tuberculosisis an infectious disease noted in bone materialsince Neolithic age. Its prevalence was influencedby poor hygienic conditions, malnutritionand domestic animals. Signs of other infectiousdiseases, leprosy and syphilis, which occurredendemically at that time, started to show in theMiddle Ages. In prehistoric populations, cariesdid not pose as big a problem as currently. Carbohydrateintake increased as late as in the MiddleAges. However, other diseases of the masticationorgan were also quite common, including:greater teeth effacement compared to moderntimes, dental calculus and paradontosis [16, 17,18]. In prehistoric and historic times, many diseasesran different courses than nowadays, werecharacterized by different range of occurrenceand severity in given populations. Introductionof new medicines, particularly appearance ofantibiotics, decreased mortality from infectiousand inflammatory diseases. One should notethat not all disorders leave traces on the skeletonand many diseases might be missed duringsuch studies.Skeletal material from Poland bears signs ofintentional procedures: amputations and trepanations.While examining anthropologicalReview articlematerial, we can observe the process of developmentof interventional medicine. Trepanationsconstitute a broad issue and skulls with signs oftrepanation coming from Poland are dated backto Neolithic Age, through the Bronze Age, earlyIron Age, up to the Middle Age. However, signsof amputations are present only on the skeletonsfrom Middle Age due to the fact that itwas a very dangerous procedure associated withhigh risk of infection and there were no effectivemethods of stopping hemorrhages. Anothergroup of intentional procedures are permanentdeformations, which in Poland involved theskull. Two deliberately deformed skulls werefound – one coming from Neolithic Age (theNew Stone Era), the other from medieval times.They were both elongated in the lateral aspect,the forehead shifted posteriorly. Therefore, thiscustom was incredibly rare in Poland. Possibly,those individuals did not belong to local societies.Using bandages or wooden boards to exertpressure against the occipital, frontal or bothskull regions altered the shape of the head. Performedin children, deformation changed skullproportions, particularly the length-to-width aswell as height ratios [19].Skeletal material obtained from medieval cemeteriesindicates that people were able to reduceand stabilize fractures at that time. Certainly, thestate and extent of such knowledge depended ongiven human populations. Undoubtedly, it waspassed orally from one generation to another.Properly reduced fractures provide evidence ofappropriate therapeutic techniques. Fractureswere stabilized in wooden slates padded withmoss and tied with a bandage [20].In modern neurosurgery, skull trepanationinvolves drilling a hole to uncover the meningesand brain in order to perform a specific surgicalprocedure or evacuation of hematoma. Trepanationholes are made using a trepanation drill.One or more orifices are drilled during lobarskull opening [21]. In anthropology, trepanationis understood as intentional opening of cranialcavity through drilling, scraping or cutting fourincisions. The reason for opening the cranial cavitywas not to perform neurosurgical procedures,although it was probably a way of evacuatinghematomas. In Poland, eight skulls bearing signsof trepanation — 5 male and 2 female — comefrom Neolithic era (the new Stone Age — from114 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 115 – 118Magdalena Cybulska at al.: Anthropological and archeological sources …about 5400 until 2200 /2100 B.C.), five — allmale — from the Bronze Age (from about2200 /2100 until half of 8 th century B.C.), six – 4male and 2 female – from Early Iron Age (fromthe second half of 8th century B.C. until the endof 7th century A.D.), and about twenty-eight — 16male and 6 female — come from the Middle Ages(from the 7th century until half of 14 th centuryA.D.). It should be noted that determining thesex of the buried person was not always possible.Larger number of skulls with signs of trepanationprobably resulted from increasing populationdensity, formation of large settlements andcities and, therefore, greater need for medical aid.Most trepanations were performed in men. Itwas probably related to the fact that men wereat greater risk of head traumas and injuries, e.g.during hunting, battles and fights. It is consistentwith earlier epidemiological studies showingthat, both in the Middle Ages and nowadays,men are more prone to traumatic injuries. Inthe medieval times, the number of skull injuriesin men increased almost threefold.However,this relationship was not observed in women[22]. Skulls with trepanation holes were mostoften adult, although there were few belongingto young people or the elderly. Naturally, oneshould emphasize that the ages of these individualswere determined at the time of death. If theorifice is not obliterated, one may conclude thatthe person died during the procedure and the ageat the time of death is consistent with the age, atwhich trepanation was performed. However, ifthe opening is well obliterated, it is then difficultto estimate the age range, within which trepanationwas performed. Obliteration may be a proofof patient’s survival for several months or years.There are no children’s’ skulls bearing signs oftrepanation in the materials obtained in ourcountry. Possibly, this kind of procedure wasrarely performed in young individuals. Fragilechildren’s skeletons are quickly decomposed,which is the reason why the signs of trepanationare poorly visible. It is also likely that childrendid not suffer from conditions, which couldbe considered indications for such procedures.Possibly, children less often fell victims to severehead injuries in the past. However, such procedureswere performed during the Greek-Romantimes. In this region of the world, doctors werefamiliar with the works of Hippocrates andhttp://military.isl-journals.comGalen, who mentioned trepanation as one oftherapeutic methods [23].There are also very few trepanation skulls fromthe Bronze Age and Early Iron Age found inPoland. It could be related to the custom of bodyburning (cremated human remains are placedin an urn or directly in the grave), as it is muchmore difficult to recognize changes related to diseaseor surgical procedures in burnt remains.Trepanation was most often performed in thearea of parietal (more often on the left side) andfrontal bones, rarely on the occiput. Trepanationholes rarely involved more than one bone. In thestudied cases, holes were located at the top of thehead or at a lateral surface of the skull – in suchcases they involved the squama of temporal boneand occiput. Trepanation holes rarely overlappedwith cranial sutures, although there were few suchcases collected in Poland. Surgeons probably distinguishedbetween cranial sutures and bone fractures.Sizes of trepanation holes vary. Some areextensive (5-6 cm in diameter), while other onesare small (less than 1 cm). Trepanned skulls collectedfrom Poland area most often contain onlyone hole. In two cases from neolithic times andtwo cases from the Middle Ages, we were dealingwith two holes. No skulls with multiple trepanationholes were obtained from Polish region. Thesize and positioning of trepanation hole was certainlyrelated to the location and extent of injury(in posttraumatic trepanations), but it could berelated to the site, where the patient experiencedpain, treatment method and applied tools.In Poland, since the neolithic period until MiddleAges, trepanations were performed throughscraping and cutting. The first method was safer,as it was associated with lower risk of brain damage.Tools with a cutting edge were used, butonly for scraping the bone. Tool motion couldbe performed in a vertical or horizontal motion.Sometimes, both methods were used togetherand both neolithic and medieval skulls bearsigns of such procedures. Literature emphasizesthat the cutting method was used for acquisitionof bone talismans (from the dead), althoughthere are skulls found in Poland with trepanationholes indicating that this method was alsoused for therapeutic purposes, particularly inthe medieval period and at the turn of MiddleAges and the modern era.115

© Military Pharmacy and Medicine • 2012 • 4 • 116 – 118Skulls containing trepanation holes constitute asubject of scientific studies since 19th century.Literature cites, that the most frequent bodilyinjuries are head traumas, which involve 60% ofgeneral population [24]. In the prehistorical andmedieval periods head traumas were probablyalso very common, which was likely related tobattles, fights and hunting.Often, due to poor skull condition, it is difficultto establish the indications for trepanation,particularly when the skull does not containany external signs of trauma. Also, illnessdoes not always leave marks on the skeleton.However, most trepanation procedures wereprobably performed for therapeutic reasons,in order to remove the fractured bone. Suchprocedures were often performed intuitively.Leverage and removal of fractured bone fragmentor fragments, as well as polishing of sharpwound edges could bring immediate effectssuch as regression of neurological disorders orreturn of consciousness, as fragments of thedamaged bone ceased to exert pressure againstbrain tissue.Therefore, procedures were repeated in subsequentcases. First of all, treatment was aimed atremoving the source of pain, which could havebeen caused by various pathological changes.Medieval skulls bear the signs of trauma particularlyoften. Such procedure was not easyto perform. It must have been done by a medicexperienced in this field and equipped withappropriate tools. Indications for skull trepanationalso included: pericerebral hematomas,inflammatory lesions or brain tumors.Several skulls described in Polish anthropologicaland archeological literature as trepanned,are not such. Holes present on those skullscould have been made during excavations (skulldamage by a probe), as a result of processes takingplace in the soil, traumatic injuries, gunshotwounds or post mortem examinations (ifthe hole involves the entire or almost entireskull cap). Therefore, not all skull aperturesshould be considered purposeful therapeuticprocedures. Particularly, very small openings,2-3 mm in diameter [25], or very large onesinvolving several skull bones indicate that theyhave not been made during an intentional surgicalprocedure.Review articleAnother interesting issue concerns the problemof patient survival following trepanation. Manypublications indicate that the fraction of successfulprocedures was high. Data on trepanationskulls from South America point to osteal reactions(signs of obliteration) in 55% to 70% of trepannedskulls [26]. In cases of trepanation fromthe area of Poland, Czech Republic and Slovakia,professor Adam Paluch states that the successrate amounted to about 81.7% [27].Authors of publications on trepanations fromthe neolithic times performed in Denmark andGermany report 80% (Denmark) and 88% (Germany)survival following trepanation [28]. Possibly,such high survival rates were related topatient care following the procedure, wounddressing and use of newly made flint and stonetools, which constituted sterile medical instruments.The reasons for this include strong immunologicalsystems of individuals subjected to theprocedure (weaker individuals died in childhood).Survival after surgery also depended onpatient’s general condition, extent of injury ordisorder constituting an indication for trepanation.Smaller openings certainly posed a smallerrisk of wound infection. It is also possible thathigh survival rates following these proceduresare associated with the fact that most of historicaltrepanations were epidural. Complicationsof this procedure included wound infection, butalso intraoperative bleeding and meningeal orbrain injury. They resulted from unskillful tooluse and poor surgical technique. In the 19th andat the beginning of the 20th century trepanationswere carried out in hospitals, which were characterizedby poor hygienic and sanitary conditions.Therefore, mortality among patients undergoingthis procedure was high.One could also ask, who performed such proceduresin the prehistorical and historical times?In large societies, knowledge of medicine andsurgical procedures was passed from one generationto another. Experiences gained in performingsuch kinds of surgeries allowed foravoiding brain and meningeal injuries or infections.During the Iron Age (La Tene period)trepanations were most likely performed by“warrior surgeons,” as evidenced by their funeraryitems, which included medical tools, besidearmament. They were probably able to performother minor surgical procedures. In the La Tene116 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 117 – 118Magdalena Cybulska at al.: Anthropological and archeological sources …period, the wounded and sick warriors werealso cared for by their companions. Based onarcheological findings, we may conclude thata “warrior-surgeon” was equipped with medicalinstruments, including the following tools:bone knives, exploration probes and hooks. Inancient civilizations, with development of theart of war and formation of armies, comes thegradual progress in the areas of medicine relatedto military actions and frequent injuries, particularlysurgery. Surgical skills and treatment ofinjuries and wounds were especially importantin carrying for wounded warriors. During theRoman period, trepanations were performed bymilitary doctors (specially trained) that accompaniedthe legions.Military surgery went through many stages ofdevelopment. In the Roman army, a qualifiedmilitary doctor replaced a warrior-surgeon ofthe La Tene period. When it comes to the RomanEmpire, we are able to identify the doctor or amedic based on archeological studies and funeraryequipment. However, in the Barbarian regionidentification is very difficult. Three burial sitesfrom the Iron Age were identified in Poland,which contained tools described by the archeologistsas medicine-related. Two graves belongedto warriors and one is thought to be a burial sitebelonging to a midwife [29, 30]. There was probablyalso folk knowledge regarding trepanationsand other surgical procedures. People involvedin the surgical craft benefited from this knowledge.In the Middle Ages, as a result of separatingsurgery from medicine, surgical occupationcould be undertaken by people without medicaleducation, who only possessed some practicalskills. However, it is emphasized that barbersperformed mainly minor surgical procedures,healed wounds, reduced dislocations and fracturesor opened abscesses. They could also learnabout medicine from the clergy, as their work alsoincluded shaving tonsures. In the Middle Ages,demand for surgeons was high. They workedin the cities and princes’ courts. Ethnographicsources inform us that some occupations werealso predestined to performing therapeutic oreven surgical procedures, including: blacksmiths,shepherds, carpenters and beekeepers [31].People who cared for animals could use theirmedical knowledge to perform certain procedureson men. The tools used by the mentionedhttp://military.isl-journals.comcraftsmen for their everyday work could also beuseful for various medical procedures. In case ofa blacksmith, the transformation of metals intospecific items was particularly important, as itwas attributed somewhat mystical properties, asin the case of transition from illness to health.Trepanation skulls, dated back to 11th and 14thcenturies, were also found in the medieval Cracowarea. In case of a 14th century skull, theprocedure could have been performed by eitheran experienced surgeon or a craftsman. Betweenthe 16th and 18th century, guild surgeons werefamiliar with the trepanation technique, butrarely used it. It probably resulted from fear ofpatient’s death. The only indication for trepanationincluded severe head injuries [32]. It was away to decrease intracranial pressure or removean epidural hematoma. In case of trepanationskulls from the turn of medieval and moderntimes, we may suspect that a guild surgeon or acraftsman performed that procedure.Skeletons bearing signs of amputations alsocome from medieval cities: Wroclaw andGdansk. Amputations performed by guild surgeonswere also considered dangerous and wererarely performed.The picture of medicine in Poland, which maybe reconstructed on the basis of archeologicaland anthropological material indicates that,since Neolithic period, people tried to use everythingfrom human environment for medicalpurposes: curative water springs (votive offeringsfound there indicate that contemporary societiesascribed the springs healing and magical properties),medical plants. They also made the first flintand stone tools for trepanation and other minorprocedures. Therefore, we may note the evidencethat surgery, herbal medicine and hydrotherapyhave been shaping since prehistoric times. Archeologicalrelics and skeletal material certainlygive only a fragmentary picture of medicine inPoland in the prehistoric and medieval times.Despite that, they constitute an important sourcein the studies of medical historians. Knowledgeof medicine was passed from one generation toanother in small, often isolated, societies. Medicine,magic and religion coexisted throughoutthe ages and some magical/therapeutic practiceswere still popular among rural populations at thebeginning of 20th century.117

© Military Pharmacy and Medicine • 2012 • 4 • 118 – 118References:1. Topolski J. Metodologia historii. PWN; Warszawa 1968.2. Kaczanowski P, Kozłowski K. J. Wielka historiaPolski. Najdawniejsze dzieje ziem polskich. Tom1.Wydawnictwo Fogra; Kraków 1998.3. Piontek J. Biologia populacji pradziejowych.Wydawnictwo Naukowe UAM; Poznań 1999.4. Lisiewicz J. Zagadnienia prehistorii medycyny wświetle antropologii archeologicznej i paleopatologii.Archiwum Historii i Filozofii Medycyny. 1970;33:145-161.5. Wierzbicka D. Zagadnienia paleomedycyny na Śląsku.Prace Medyczne 1977-1978. Opolskie TowarzystwoPrzyjaciół Nauk. Wydział Nauk Medycznych. 1980: 5.6. Gryglewski W. R. Paleopatologia w badaniachhistoryka medycyny. In: Meissner R, editor. Medycynai farmacja XIX i XX wieku; Poznań 2007.7. Malinowski A. Zmienność chorób zębów umieszkańców ziem polskich w przeszłości. ArchiwumHistorii i Filozofii Medycyny. 1979; 42: 463.8. Gładykowska-Rzeczycka J. Lecznictwo u Słowian.Sztuka i Medycyna. 1993; 3(1): 4-5.9. Biegeleisen H. Lecznictwo ludu polskiego. PAU;Kraków 1929.10. 10. Latałowa M, Jarosińska J, Badura M. Elblągśredniowieczny w świetle dotychczasowychmateriałów archeobotanicznych. Archeologia Polski.1998; 43: 145-166.11. 11. Zemanek A, Wasylikowa K. Historia botanikii archeobotanika w poszukiwaniu danych oużytkowaniu roślin w średniowiecznym Krakowie.Analecta. Studia i materiały z dziejów nauki. 1996;5:123-138.12. Badura M, Latałowa M, Jarosińska J, Święta J. Roślinyużytkowe w średniowiecznych i nowożytnychmateriałach archeobotanicznych z miast północnejPolski (Kołobrzeg, Gdańsk, Elbląg). In: Czaia R,editor. Archaeologia et Historia Urbana; Elbląg 2004.13. Brongers JA. Ancient Old-World TrepanningInstruments. Berichten ven de Rijksdienst voor hetOudheidkundig Bodemonderzoek. 1969; 19: 7-16.14. Woźniak Z. Celtowie w Polsce. PWN; Kraków 1968.15. Kirkup J. The evolution of the surgical instrumentsfrom ancient times to the twentieth century. NormanPublishing. California 2006.16. Gładykowska-Rzeczycka J. Schorzenia swoisteludności z dawnych cmentarzysk Polski. PrzeglądAntropologiczny. 1982; 48: 44.17. Gładykowska-Rzeczycka J. Schorzenia ludnościprahistorycznej na ziemiach polskich. Gdańsk 1989.Review article18. Kwiatkowska B. Mieszkańcy średniowiecznegoWrocławia. Ocena warunków życia i stan zdrowiaw ujęciu antropologicznym. WydawnictwoUniwersytetu Wrocławskiego; Wrocław 2005.19. Tubbs SR, Salter GE, Oakes JW. Artificial deformationof the human skull: a review. Clinical Anatomy. 2006;19: 372-377.20. Jankowski J. Historia medycyny średniowiecznejw Polsce. Człowiek, populacja, środowisko. PraceDolnośląskiego Centrum Diagnostyki MedycznejDolmed we Wrocławiu. Wrocław 1988.21. Mazurowski W, Ząbek M. Neurochirurgia. In:Bielecki K, editor. Narzędzia, protezy i szwychirurgiczne; Warszawa 1995.22. Strona internetowa http://global.sbs.ohio-state.eduGlobal History of Health Project23. Mariani-Costantini R, Catalano P, di Gennaro F, diTota G, Angeletti LR. New light on cranial surgery inancient Rome. Lancet. 2000; 22(355): 305-307.24. Chmurzyńska A, Kantor I, Jurkiewicz D. Urazy kościskroniowej. Lekarz Wojskowy. 1999; 75(3-4):173.25. Andrzejowski J, Stanaszek ŁM, Mańkowska-PliszkaH. Modła, grób 169-pierwsza trepanacja czaszkiz okresu wpływów rzymskich z ziem polskich.Wiadomości Archeologiczne. 2006; 48: 185-199.26. Żukiel R, Jankowski R, Stachowska-TomczakB, Blok T, Wieloch M. Operacyjne leczenieurazów czaszkowo-mózgowych w Ameryceprzedkolumbijskiej. Neuroskop. 2001; 1(3): 74.27. Paluch A. Ślady występowania zabiegówtrepanacyjnych na ziemiach Polski i Czechosłowacjiw starożytności i średniowieczu. Archeologia Polski.1975; 20: 411-454.28. Piek J, Lidke G, Terberger T, Von Smekal U, Gaab MR.Stone Age surgery in Macklenburg-Vorpommern: asystematic study. Neurosurgery. 1999; 45: 147-151.29. Biborski M. Dalsze ratownicze badaniawykopaliskowe na cmentarzysku kultury przeworskiejz późnego okresu wpływów rzymskich i wczesnejfazy wędrówek ludów w Mokrej, woj. śląskie. Badaniaarcheologiczne na Górnym Śląsku i ziemiachpogranicza w latach 2001-2002; Katowice 2004:125-130.30. Demidziuk K, Kokowski A. Żukowice, pow.Głogowski, woj. dolnośląskie, grób 41. In:Wandalowie strażnicy bursztynowego szlaku. Lublin-Warszawa 2004, s.290.31. Półtorak Z., Lecznictwo ludowe rodzinnej ludnościOpolszczyzny. Instytut Śląski; Opole 1989.32. Sokół S. Historia chirurgii w Polsce. Cz. 1. Chirurgiaokresu cechowego. Wydawnictwo PAN; Wrocław 1967.118 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 119 – 122Radosław Ziemba: Bioterrorism — nature of the problemEmergency medicineBioterrorism — nature of the problemRadosław ZiembaMilitary Centre for Pharmacy and Medical Technology in Celestynow, PolandAuthor’s address:Radosław Ziemba, Military Centre of Pharmacy and Medical Technique, ul. Wojska Polskiego 57,05–430 Celestynów, Poland; e–mail: zx11@op.plReceived: 2012.07.12 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:In the 20h century, terrorism became a threat to international safety. Over the past 100 years, terrorismbecame transformed and became a factor to a large extent determining the sphere of political, economicaland social relations on local, regional and international levels. Advancing globalization and accompanyingprogress in the field of IT and telecommunication technologies facilitated emergence of newforms of this phenomenon and widening of its spatial scope.Key words: terrorism, biological weapons, biological weapons development programs.We should seek the genesis and beginnings ofbioterrorism much earlier, although all forms ofits employment fall, in a more intense shape, atthe turn of the 20th and 21st century. Its issues,essence and nature should rather be combinedwith, rather than detached from, generally understoodterrorism. Experts on the issue associatethis phenomenon, which is now widespread andconsidered one of the main global problems, witha symptom of “degeneration of war.” A growingnumber of civilian casualties constitute its illustration.Degeneration of war is accompanied bya tendency described by Boleslaw Balcerowicz as“lowering of war threshold” [1]. It is an inclinationtoward conducting warfare against a populationof people completely uninvolved, intentionallyat least, in any military conflict. Such actionsare called “quasi wars” and their toll is based onthe lack or low level of awareness among civilianpopulation in a given region, city or territory of agiven country. Destructive actions are no longerreserved for states, as main players in internationalrelations and subjects of internationalpublic law. Suitably prosperous, although poorlyhttp://military.isl-journals.comarmed ideologist or even an ideological maniacplaying on fanaticism can evoke a conflict on aninternational scale. With that, he can perform adetonation not only in its mechanical sense, butalso detonate the sense of common, individualand personal safety and introduce a broadlydefined psychosis of fear.Despite multiple publications on terrorism, it is difficultto establish a uniform definition of this phenomenon.It should be noted that there are abouttwo hundred expressions in the whole literature.Phonetically, it is almost identical in all Europeanlanguages and therefore, understood by everyone(fr. terrorisme, sp. terrorismo, rus. terrorizm).Two definitions should be mentioned in relationto the problem of bioterrorism as an acceptedfaçade of broadly defined terrorism. One of themis taken from an encyclopedia (published byPWN in Warsaw in 1993, page 864), defining terrorismas: “ an activity of small extremist groupsthat, through murder, death threats, politicalmurders, kidnapping of hostages or planes and119

© Military Pharmacy and Medicine • 2012 • 4 • 120 – 122similar means despised by the internationalcommunity, try to turn public attention to theirstatements or to force governments to succumbto their demands.”The other definition was created in 1996 by theFederal Bureau of Investigation and defined terrorismas: “unlawful use of force and violenceagainst people and possessions (ownership) inorder to frighten or force the government, civilianpopulation or any other sector of the statesystem to support political or social demands.”All definitions contain two fundamental elements:“fear” and “forcing behavior.” Moreover,a definition of a terrorist used by the Oxforddictionary emphasizes that a terrorist act is:“planned, calculated and premeditated” [2].Due to a growing demand among terrorists forattacks associated with an increasing numberof casualties and easier access to materials andtechnologies used for production of weapons ofmass destruction, we should conclude that theprobability of using chemical, atomic or biologicalweapons by terrorists is growing and becomesmore and more substantial.In contrast to chemical substances, biologicalmaterial (viruses and bacteria) is characterized bythe ability to reproduce and mutate. As a result,they become increasingly more dangerous andresistant with time. A single bacteria is capable ofdividing every 20 minutes. After 10 hours, we canobtain a billion of daughter cells. It directly followsthat it is relatively easy to produce a weaponcapable of killing millions of people.Anthrax bacilli (Bacillus anthracis) attack mainlysheep, cows and goats, which become infectedthrough the oral route. Bacteria is transmittedthrough water, insects, wild animals or birdsand their excretions. Human infections are rare.About 95% of cases constitute lighter forms of thedisease involving the skin. When (5% is sufficient)anthrax invades the lungs, patient usually dies.Bacteria are not transmitted from one humanto another and patient isolation is not necessary.Vaccines partially protect from anthrax, but theymust be administered repeatedly.On the basis of American simulations regardingthe toxicity of anthrax it was concluded, that anReview articleairplane drop of 50 kg of bacteria from 2000 monto a city with a population of 500 thousandpeople would result in 135 thousand of infectedpatients, 90 thousand of which would die [3].Relatively simple equipment, such as ordinaryfermenters, is needed for growing bacterial culturesand obtaining pathogens and toxins doesnot pose any problems.All of these “qualities” were and are known toterrorists and attempts were made to obtain theresources for bioterrorist attacks. Armed IslamicGroup (GIA) conducted experiments in thisrespect in a biological mini-laboratory in Paris.The AUM sect was preparing for a large-scaleattack with, among other things, biological agents.They employed scientists and technicians fromJapan and Russia. Professional laboratories werearranged. The sect was partially ready for productionof biological weapons, including anthrax, avery contagious disease called Q fever and probablythe deadly Ebola virus. Seriousness of thethreat is evidenced by the fact that it owned a special,double-turbine helicopter Mi-117 equippedwith instrumentation for chemical spraying. Italso conducted first biological attacks.In 1990, using a sprayer of their own construction,terrorists attacked Tokyo downtown withbotulin toxin. It turned out to be ineffective, butthere were two repeated attempts the same year.The scope of biological weapons used by terroristsincludes, beside the previously mentionedanthrax, botulin (also known as “sausage poison”),plague and smallpox. The latter, eradicatedaround the world in 1980, is still stored in twoplaces: Atlanta (USA) and Kolcovo (Russia).There are currently several visions of the worldthreatened by lab-modified microbes. Professors:Claire Fraser from Institute for GenomicsResearch in Rockville (Maryland) and MalcolmDando from the University of Bradford in GreatBritain are warning on the pages of “NatureGenetics” that rapidly progressing works ondecoding microbial DNA can serve developmentof new varieties of difficult to detect microorganisms,for which there are no vaccines or drugs.It is estimated that as soon as this year or in twoyears at the latest we should learn the sequenceof nucleotides of over 70 viruses and bacteria.Last year, molecular biologists drew a DNA120 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 121 – 122Radosław Ziemba: Bioterrorism — nature of the problemmap of cholera, listeria (causing gastrointestinalinfections), leprosy (evoking fear in the anticand medieval times) as well as one of the mostdangerous bacteria, Streptococcus pneumoniae– an etiological factor of pneumonia, meningitis,otitis media and peritonitis, which kills over3 mln children each year and increasingly oftenbecomes resistant to antibiotics [4].These studies can be used for development of newdrugs as well as for better understanding of evolutionarymechanisms. Similar to atomic energy,it can be used both for the benefit of people aswell as against them – e.g. development of lethalbiological weapons. Such experiments are alreadybeing conducted. As early as in 1999, ProfessorMalcolm Dando cautioned in his book “BiotechnologyWeapons and Humanity” that developmentof a biotechnological bomb directed againstspecific populations (e.g. Arabs, Serbs, Blackmen, Kurds or Jews) would become possible duringthe next 5-10 years. Such microorganisms,like cruise missiles, can be designed for destructionof selected biological targets, e.g. peoplewith particular cell receptors or DNA sequences.It suffices to appropriately remodel genomes ofbacteria or viruses causing cholera, plague, fluor hemorrhagic fever to turn the grim visions ofscience-fiction authors into a real threat.Unfortunately, progress in the field of genetics isincreasingly more often used for development ofbiological weapons. In 1998, David Kelly, a leadingUnited Nations specialist, warned about hissuspicions that works on such type of biologicalweapon had been conducted in Iraq under codenameCamel Pox. They were directed at producingpathogens, to which only Arabs would be resistant.Effect of this research is unknown. Wonter Basson,a military biologist from South Africa accused ofconducting studies on organisms directed specificallyagainst the black population, gained a nickname“Dr. Death.” In this case, the commentatorsemphasized a clearly emerging threat. There aremultiple such causes for concern. Even followingthe attacks on New York and Washingtonand in cases of sending anthrax by post, it seemsunlikely for the terrorists to have access to moreadvanced biological technologies. However, itmust be a cause for concern that genetic modificationof pathogens is easier than anticipated. Foryears, multiple biological weapons experts arguedthat the more modifications are introduced, thehttp://military.isl-journals.comgreater the risk of pathogens becoming less viableand no longer posing a presumed threat. However,it is sometimes sufficient to introduce even smallgenetic changes to transform a harmless microbeinto a lethal pathogen.Research conducted only several months agoby Australian scientists corroborated that. Theyaccidentally created a particularly dangerouspoxvirus following introduction of only onegene into its genome. Scientists from the AustralianNational University tested a pregnancy vaccine.They used a murine poxvirus transfectedwith interleukin IL-4 gene. It was supposed toinduce formation of ovulation-inhibiting antibodies.Instead, they completely blocked rodents’immunological response protecting them againstinfections. Until now, it seemed that such manipulationscould only weaken microorganisms.Worldwide arsenals contain 43 types of biologicalweapons. Viruses, bacteria, rickettsiae (intracellularmicroorganisms) are used for their production,including genetically modified lethalpathogens, more dangerous than those discoveredby scientists in a natural environment. In1997, anthrax bacilli containing an additionalgene were developed in Russia, against whichavailable vaccines do not provide any protection.The most dangerous virus called Ebolapox wasalso developed by crossing poxvirus with Ebola.This pathogen combines exceptional infectivityand huge mortality. Ken Alibek, the former headof secret Soviet laboratory, Biopreparat, locatedin 40 cities and employing 70 thousand people,confirmed those facts during his stay in the USA.Americans conducted similar research duringthe Cold War. In 1986, as a part of over fiftybiological weapon development programs leadby the Pentagon, American scientists inducedharmless E. coli bacteria to produce anthraxtoxin within the intestine. Journalists from “TheNew York Times” exposed this fact in a bestsellertitled “Germs: Biological Weapons and America’sSecret War.” It is worth noting that this researchis still continued. On that occasion, “Der Spiegel”disclosed that there are experiments conductedon behalf of the Bundeswehr regarding productionof Yersinia pestis resistant to antibiotics [5].A Russian biologist, Siergiej Popov, who emigratedfrom Russia to Great Britain in 1992 and121

© Military Pharmacy and Medicine • 2012 • 4 • 122 – 122later traveled to the USA, revealed that he hadconducted research on microorganisms designedto confuse victim’s immunological system andlead to central nervous system auto-destruction.He took advantage of the mechanism of multiplesclerosis development, which is one of the mostdangerous disorders of central nervous system.It is an autoimmunological disease. Instead ofdestroying only foreign pathogens, immunologicalsystem causes destruction of myelin, whichis an important component of nervous sheathsfacilitating proper functioning of nerves.Is it likely that terrorists could blackmail theworld with such pathogens? Experts from “BritishMedical Journal” persuade that biologicalweapons, similar to chemical weapons, are primarilyinstruments of inducing fear.A new stage of bioterrorism expansion was initiatedat the end of September 2001. Terrorists beganto distribute anthrax bacilli in the USA (Florida,New Jersey) via mail. On the 12th of October,anthrax struck New York. Attacks were directedat people representing the media (employees ofNCB, AMI, “The Sun,” “New York Times”) andthe government (offices of United States senators).Thirty-six anthrax infections, including one fatalcase, were noted until the 23rd of October 2001.Despite difficulties associated with use of biologicalweapons as weapons of mass destruction,it evoked panic among American community aswell as in Europe. United States government evenconsidered early weaving of patent rights of BayerCo. – the only producer of ciprofloxacin, an antibioticeffective against anthrax.Not even the most absurd threat should beignored nowadays. Bioterrorism grows. TheReview articlereasons should be traced to the fact that biologicalweapons are easy to apply and transport.Their low cost can also be encouraging, as mentionedby professor Wieslaw Magdzik from theNational Institute of Hygiene in Warsaw, whowarned against it as far back as may 2001.Experiences from previous terrorist attacksnoted by the Monterey Institute of InternationalStudies show that incompetent authorities, disorganizationof rescue services, panic and poorlevel of social education are greatest allies of theattackers. To some degree, it is the price we payfor contemporary civilization. In case of ecologicaldisaster, we usually know what substances weare dealing with.A terrorist attack involves a series of unknowns.Rapid identification of the resources used by theaggressor is crucial to achieving success. Currently,hospitals introduce an electronic diseaseregistration system equipped with special software.Its job is to identify anomalies (e.g. excessivenumber of infections with particular bacteriaor viruses in a given time). A single case ofanthrax infection might not arise the vigilance ofhospital staff. However, if it appears that similarinformation flows from several hospitals, the systemwill alert the crisis management center.Words suggesting the use of various bacteria,often implying alleged possession, are most dangerousin the context of this atmosphere. Liketoxins, they invade the sense of security in alldimensions. Terrorists’ goals are often directednot so much at large numbers of casualties, but atgaining publicity and transmitting their messagethrough the media, which may bring fatal consequencesin an era of information society.References:1. B. Balcerowicz, Obronność RP a dialektyka wojnyi pokoju na progu XXI wieku, cz.I, AON,Warszawa, 2000.2. Mały oxfordzki słownik historii świata w XXw.,Puls, Londyn 1992; Raport (No 2000/02. Chemical,Biologica], Radiological and Nuclear (CBRN)Terrorism, publikacja: Comadian Security IntelligenceService (dost. on-line: www.fas.org).3. Strach przed bioterroryzmem, "Newsweek Polska",nr 7, s. 151-154.4. Z. Henisz, Biobomby, „Polityka", nr 46 z 17 listopada2001, s. 85.5. TERRORYZM – ZAGROŻENIE GLOBALNE ILOKALNE, Biuro Bezpieczeństwa Narodowego,www.bbn.gov.pl.122 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 123 – 126 Review articleEmergency MedicineAnti-drown ring – a patented drowning protection device(patent no. 197623)Jerzy MierzejewskiEmeritus Professor at the Military Institute of Hygiene and Epidemiology, Pulawy, Poland. Professor atKazimierz Pułaski Technical University of Radom, Faculty of Materials Science, Technology and Design, Chairof Chemistry, Radom, PolandAuthor’s address:Jerzy Mierzejewski, Kazimierz Pułaski Technical University of Radom, Faculty of Materials Science, Technologyand Design, Chair of Chemistry, ul. Chrobrego 27, 26-600 Radom, Poland; phone: (+48) 608286044,e–mail: mierjer@poczta.onet.plReceived: 2012.09.28 • Accepted: 2012.11.22 • Published: 2012.12.08Summary:The anti-drown ring is a device that does not restrict the user’s movements and, when activated, bringsthe critical drowning hazard situation under control and allows the user to safely remain in water.The anti-drown ring, being an inexpensive drowning protection device, should be universally availablefor water lifeguards, swimming schools, aquatic sports or open-air recreation centers, fishery and otheraquatic industries, as well as for military personnel training or operating in areas that require crossingwater barriersKey words: aquatics, equipment, rescue.IntroductionThe beginning of the summer holiday season isalways accompanied by media warnings to maintaincaution when bathing in open reservoirs.Most cases of drowning are recorded at nonattendedbeaches. These cases pertain mostly tothe youth, but also to adults, oftentimes takinga swim after drinking alcohol in quantities thatincrease risk-taking, bravado and courage showoffbehaviors.Methods of aquatic rescue to dateCompared to the development of technicaldevices that facilitate everyday life in all areas,methods of aquatic rescue used to date should bejudged in a very critical manner. Even the mostefficient lifeguards are not always able to providetimely rescue aid to the drowning person, as theequipment they have at their disposal is usuallylimited to the anachronistic life buoys and boats.Several hundred drowning cases are recordedevery year across the country, with the maximumvalue reaching as much as 600 drowningcases during a single season.http://military.isl-journals.comThis form of rescue is often to no avail, as the timebetween the alarm and the rescue is too long.Therefore, there is a need to revise the rescuemethods available to date. We should strive to be123

© Military Pharmacy and Medicine • 2012 • 4 • 124 – 126able equip the person in water with a device thatwould allow them to manage the drowning hazardby themselves, without the dramatic wait forrescue. To date, the only device of this type is thelife jacket, which restricts the movements and theease of swimming, and which is used mostly bypeople working on ships and fishing boats.The search for novelwater rescue devicesFor many years, various personal rescue devices,oftentimes automatically-triggered devicesthat could be worn by every individual stayingin open reservoirs, have been proposed. Manydevices of these type are known from Polishpatent descriptions nos. 52602, 105721, 59710,105722 and 70297Jerzy Mierzejewski: Anti-drown ring – a patented drowning protection …following complete immersion of the drowningperson under increased hydrostatic pressure thatruptures the foil surrounding a bag that is thentransformed into a life buoy.Title page of patent no. 197623 regarding theinvention titled DROWNING PROTECTIONDEVICE, as discussed in the article.Anti-drown ring design summaryWhen not activated, the anti-drown ring in questionis a thin ring made of elastic rubber tubingfreely placed around the neck and not restrictingHowever, the mechanisms to trigger thesedevices are complex and usually respond onlyFigure 2:Figure 1: Title page of patent no. 197623 regarding theinvention titled DROWNING PROTECTION DEVICE, asdiscussed in the article.124 http://military.isl-journals.comFigure 3: Figures 2-3 present the circular cross-section of nonactivatedsystem.The numbered arrows indicate as follows:1 – cross-section of the walls of the anti-drown ring;2 – tubing lumen filled with acidic reagent;3 – cross-section of ribbon with indicated bends;4 – ribbon bend inside the container filled with alkaline reagent;5 – alkaline reagent container wall;6 – alkaline reagent placed in the container with ribbon bend;7,8 – free ribbon bends in acidic reagent environment.

© Military Pharmacy and Medicine • 2012 • 4 • 125 – 126 Review articleThe principle of operationThe anti-drown ring is slightly extended andplaced on the neck by sliding it over one’s head.When at risk of drowning, the user holds on tothe device and tears it so as to unfold the foldsof the ribbon inside the containers filled withreagent 2. Unfolding the ribbon leads to the containerwalls being ruptured, leading to the releaseof the alkaline reagent (reagent 2) from the containersinto the acidic reagent (reagent 1) that fillsthe tubing.Figure 4: Figure presents a schematic circular cross-section ofthe anti-drown ring filled with gas. Of note are thewider device lumen and straightened ribbon bends.Figure 5: Figure presents a transverse cross-section of an antidrownring consisting of two parallel tubings.Mixing both reagents leads to an instantaneouschemical reaction with the release of gaswhich automatically transforms the tubing intoa pumped bladder. The quantities and rations ofboth reagents should be matched so as the formedgas extends the tubing to a diameter of ca. 10 cm.Thus, the bladder buoy formed around the neckprovides displacement sufficient to maintainone’s head above water while allowing to maintainfree movements of entire body.Figure 6: Figure presents a transverse cross-section includingthe ribbon cross section indicated by arrow 3the user’s movements in water. The diameter ofthe ring is slightly smaller than the diameter ofhuman head, which prevents the device slippingoff neck and head while making rapid movementsin water.Inside the tubing, there is a loose-fitted ribbonmade of material characterized by high resistanceto tear and to various ambient conditions.Besides the ribbon, the inside of the tubing isfilled with reagent 1, which is a solution of anacidic substance. The ribbon includes severaltightly insulated bends comprising containersfilled with reagent 2, which is a powdered alkalinesubstance.The walls of containers filled with reagent 2 aremade of material impenetrable to both materials,albeit relatively easy to tear.Explanations to figures 2-5: Figures presentingschematic cross-sections of the anti-drowndevice of the invention.http://military.isl-journals.comLoose fitting of the ribbon inside the tubing isprovided by ribbon bends not placed in containerswith reagent 2 (free bends). This solutionallows for slight expansion and multiple puttingon and removing the anti-drown ring withoutdamaging the walls of containers with reagent 2and thus triggering the unwanted chemical reactiongenerating gas when putting on the device.Such a design solution allows the resistance to befelt twice: the first time when the ribbon is straightenedout at free bends, and the second involvingthe rupture of container walls, leading to contactbetween both reagents and generation of gas.Leak protectionThe anti-drown ring made of thin rubber tubingmay be at risk of accidental puncturing. In orderto avoid such risk, the ring may be made of twoparallel tubings fitted with identical ribbons andidentical reagents.The benefits of the anti-drown ringThe anti-drown ring is characterized by the simplicityof technical solution, capability of beingput on and removed multiple times before a125

© Military Pharmacy and Medicine • 2012 • 4 • 126 – 126critical situation is encountered that requires thedevice to be activated.The incentives to start production of the antidrownring should with no doubt include lowcosts of materials required for production (rubbertubings, ribbons, reagents) and, as a consequence,low prices that would make the deviceavailable to everyone.Production and marketingof the anti-drown ringDesign preparation, production of a prototypebatch and initiation of production would requireefforts to obtain funds from state or EuropeanUnion budget allocated to water rescue, or fromprivate sponsors.The prototype series should be made in orderto raise interest of sponsors so as to acquirefunds required for the development of technicalsolutions for serial production of the antidrownrings. Semi-technical scale implementationworks should be made in institutes (plants)developing rubber industry machinery.The next marketing stage would involve the promotionalcampaign, mostly in the media as wellas in the water industry aquatic sports and recreationcenters, the military, the police and publicschools of all levels.The promotional campaign should include presentationsin shopping centers and at the aquaticsports and water rescue equipment trade fairs.After the anti-drown rings are well accepted bythe general public, technical solutions should bedeveloped so as to allow automated mass productionof the devices.Mass marketing of anti-drown ringsWith mass-production capabilities available,promotional campaigns should be organized atJerzy Mierzejewski: Anti-drown ring – a patented drowning protection …the national and international aquatic sports andwater rescue equipment trade fairs.Likewise, long-term educational campaign shouldbe started to promote the benefits of such a simpledrowning protection device. Trainings should beprovided mostly to individuals spending free timeat or working on open water reservoirs.Strategic goals of thepromotional campaignDissemination of social awareness of the benefitsof using the anti-drown rings.Introduction of legal obligation to use antidrownrings by individuals staying in openwater reservoirs.The ultimate goal would be to reduce the annualnumber of statewide drowning cases from severalhundred to not more than several dozenaccidents (wintertime and flood drowning).The obligation to use the anti-drown rings wouldlead to a great change in the profile of water rescueactivities by limiting the latter to educationaland preventive activities, including the controlwhether individuals staying in open water reservoirwear the rings.The planned strategic goals may be achieved byconvincing entrepreneurship-supporting institutionsand decision makers about the attractivity ofthe device, obtaining funds for prototyping, promotion,trainings and initial production stages.Depending on the societal interest and demand foranti-drown rings, mass-scale production shouldbe undertaken so as to meet the market demands.As the experience in using the anti-drown ringswould grow, the proposed model might be modifiedprovided that the general principle of operationand use remain unchanged.126 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 127 – 132 Short CommunicationHistory of medicineSpeech made by Commandant of the Military Centre forPharmacy and Medical Technology in Celestynów, Colonel DMScRadosław ZiembaRadosław ZiembaMilitary Centre for Pharmacy and Medical Technology in Celestynow, PolandAuthor’s address:Radosław Ziemba, Military Centre of Pharmacy and Medical Technique, ul. Wojska Polskiego 57,05–430 Celestynów, Poland; e–mail: zx11@op.plReceived: 2012.12.022 • Accepted: 2012.12.02 • Published: 2012.12.08Ladies and gentlemen!We have an honourable opportunity to attend theceremony of Mr Colonel Krzysztof KONDRACKIparting with the uniform of the Polish Army.This ceremony is all the more solemn as it fallson 29 November – Day of Officer Cadet, whichFigure 1: Col Radosław ZIEMBA, M.D., Ph.D., the Commander of the Military Center for Pharmacy and Medical Technique, awards a saber on behalf ofthe staff of the Center to Col Krzysztof Kondracki, M.Sc. (Pharm.), as a symbol of bravery of the Polish army and of military duty and loyalty.http://military.isl-journals.com127

© Military Pharmacy and Medicine • 2012 • 4 • 128 – 132Radosław Ziemba: Speech made by Commandant of the Military …Figure 2: Col Krzysztof Kondracki, distinguished by the Commander with a photo against the background of the Bannerof the Military Center for Pharmacy and Medical Technique.Figure 3: The Commander of the Military Center for Pharmacy and Medical Technique awards an encyclopedia to Col Krzysztof Kondracki.128 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 129 – 132 Short CommunicationFigure 4: The retiring Col Kondracki gives a speech to the guests attending the event.is a special day for every officer. The officer cadetperiod is an introduction to an officer epic, andMr Colonel started the latter on 31 June 1978with studies at the gen. Bolesław Szarecki MedicalMilitary Academy in Łódź at PharmaceuticalFaculty. It’s worth adding that he simultaneouslystudied pharmacy at the then existing MedicalAcademy (civilian university) in Łódź.He began the studies after obtaining a certificateof secondary education at Frédéric Chopin SecondarySchool in Sochaczew.I wish to add that Mr Colonel Kondracki hascontinued the traditions of the officer ethos, ashe was born into the family of an officer whoserved in 32nd regiment of fighting and reconnaissanceair forces in Sochaczew. It is with thistown that Mr Krzysztof bound his life from hisbirth, through Primary School, until he obtainedhis certificate of secondary education.On Łódź Soil he made important decisions of hislife, as in January 1982 he married Wanda, herehttp://military.isl-journals.comhis son Maciej was born, now also a holder of anMPharm degree. From 10 May 2010 to 6 May2011, his son participated in the 7th change ofPolish contingent in Afghanistan. Thus, Mr Kondracki’sson is also continuing the family traditionsin some way.As far as the children are concerned, the hero oftoday’s celebrations adopted gender parity a fewyears ago, as in April 1985 his daughter Agata wasborn in Celestynów – now as a physiotherapist.It is with Celestynów, or the Military Centre forPharmacy and Medical Technology to be precise,that he bound his first eight years after completingthe studies and gaining the rank of an officeron 26 June 1983. In 1986, he was commissionedas a lieutenant (as a section manager), and in1989 – as a captain. From 18 November 1991 hebound his life with the Central Clinical Hospitalof Medical Military Academy at the post of a seniorpharmacist where in 1993 he was promoted tothe rank of major at the post of deputy managerof the pharmacy and from 23 February 1996 he129

© Military Pharmacy and Medicine • 2012 • 4 • 130 – 132took up the post of the manager of the pharmacyand was promoted to the rank of lieutenant-colonelin 1998.On 12 May 2003 he became the Manager of theBase at the already existing Military Institute ofMedicine. Then, on 1 April 2007 he joined theInspection Office of Military Health Care at thepost of deputy Chief Pharmaceutical Inspector ofPolish Army and was commissioned as colonel.At this post, at this pace and with this rank, heserved until 15 October 2012.Mr Colonel earned high recognition and respectthrough his self-discipline, tact, loyalty, authorityamong colleagues, principled attitude to hisservice, tactful style of behaviour among coworkers.Always modest, genuine, without excessivepretensions or elation. He always showedRadosław Ziemba: Speech made by Commandant of the Military …helpfulness and responsibility, fulfilling a discursiveapproach to the idea of officer and pharmaceuticalethos. You are, Mr Colonel, a Paracelsusin the uniform for us.Mr Colonel, a specialist in many areas of pharmacy– especially military one – we have immortalizedyou in a photograph against a backgroundof the banner of the Military Centre for Pharmacyand Medical Technology in Celestynów. Itis there that you started your initiation into theservice.We also have the great honour to hand this pieceof cold steel called a sabre. Having different patterns,through centuries it lighted with the flashof the blade often heroic deeds of the Polish army,accompanied cavalry troops, and today adds colourto parades, state and military celebrations.So let it be in your hands the symbol of fulfillinga soldier’s duty and loyalty in the officercommunity.Let the motto engraved at its handle:“A reliable friend is recognized in an uncertain situation…”determine your acts in this stage of life.130 http://military.isl-journals.com

© Military Pharmacy and Medicine • 2012 • 4 • 131 – 132 Short CommunicationIMĆ Panu PułkownikowiKrzysztofowi KONDRACKIEMUidącemu w nowy seans życia„pod kapeluszem”Akt one, scena pierwszaPrzez dyskretny otwór w kurtyniewejrzeć tylko w zakulisy wierszaz historii losu spojrzeć o pustej godziniekiedy widownią są oczy, a uszy słuchowiskiemi cienie rzęs na uboczuwięc rozprawimy się z jednym nazwiskiemza którym stoi ten oto…Krzysztof zawinął bieg swojej historiichoć wszystko w niej bywa odmienne.Tak pewien dzień październikaw tysiąc dziewięćset pięćdziesiątym dziewiątymwyłonił go nam na tę ziemię.Waga mu rysy rzeźbiła na twarzykiedy wodził oczyma po sochaczewskim niebie.Tamte twarze szkolnego ornamentutamta pamięć ust jak pieczęci,grona pedagogów, edukacji momentów.W cenzurze świadectw różne uczniowskie chęci,Tropem w czasy dojrzałe, lato ciała,spokój pajęczany, krzewy obute w kiścikołysały beztrosko – niebieskie lata młodości.W szkolnych wierszach bagnetów strome błyskawicetam nasza chluba i naszych możliwości granice,co noc pośród latarni szukało się srebrnych kawiarniw dzień nad biurkiem trzeba było się zgiąć,pod kluczem szopenowskich nut ksiąg…Przyszedł dzień, kiedy strugi mazowieckiego śwituwysłały w misję wyroku Dioskurydesa przesłaniena łódzkim bruku podchorążacko — studenckieślubowaniesłowa Gaudeamus, żołnierskiej przysięgicyzelowały drogę do etosu oficerskiej wstęgi.W panteonie dwudziestego wieku.Powroty z balów, dyskotek, klęsk, wypraw krzyżowychskacząc przez Pietrynę jak po kolorowych krach,unosząc potem drewniane powieki,przechodząc niebieską granicę w alchemii farmaceutycznychpraw.Od Hipokratesa idei do FarmakopeiPrzy egzaminie – Panie Boże zbaw.Akt two, scena drugaNa ozłoconym przez bliskość balkoniePani Wanda założyła dłonieniech mnie Krzysztof z nadziei wybawiw przestworzach mojego świata się zjawizimowego stycznia szesnastegozłotych obrączek ikonaoświetlała marsza Mendelsona…W sierpniu zszedł z niebiosaMaciej, syn łaskawy, pociecha rodzicówjako w maju rosa co pada na trawy,cicho zszedł w objęcia do komnaty matkijak majowa rosa co pada na kwiatkinazwisko jak totem utrwalone potem.Nie zapominaj jaka to siław czerwcowe słońce gwiazdki zdobyłaetos olśniła i animuszu do farmacjidodała Panu od wtedy co chwila.Z tego posłania od łódzkiej ziemiw Celestynowie między nowemi.Akt three, scena trzeciaTaki to czas był, co dzierżył w swej treścimłodości radości i dobytek mnogidziecięciom płaci w lasach mazowieckichodtąd z Agatką przechodziłeś wszystkie drogi.Czasy edukacji, tym razem dla dziecico troską ojcowską trzeba było cieszyć.Można by wieczność zobaczyć wśród nocykiedy się z wojskową farmacją połączyłjak wielki pierścień życia nieskończonej mocyna tło ogromnych cieni do tej właśnie sprawyrzucono kapitana w konszachty Warszawy.Jak u światłych ludzi czasem bywa,przyszła kariera nawet całkiem błyskotliwa.Czasem tony przedziwne bezrozumnej skargi,obok nich jak z lutni fantazje i fraszkiróżnej cierpkości dowcipnego lotu igraszki.Obok nich pokłony i uciech zasadzki wszelakie,cierpkie lecz drogie, jakby skarby jakierozpraszają człowieka , z doświadczeń bogaty.Nadziejo święta, pokoro wysokajak szczyt niebios wśród planet pochoduTwój wielki szlak jest wskazany dla okaTy znajdziesz gniazdo jak ptak opierzonywyfruniesz łatwo, sam to dostrzec zdołasz.Powracaj znów zatem w Celestynowskie strony…Krzysztof BarczewskiAnno domini 29 listopada 2012http://military.isl-journals.com131

© Military Pharmacy and Medicine • 2012 • 4 • 132 – 132Radosław Ziemba: Speech made by Commandant of the Military …132 http://military.isl-journals.com

© Military Pharmacy and Medicine EDITORIAL POLICY AND GENERAL INFORMATIONEditorial policy and general informationMilitary Pharmacy and Medicine is an international, peer-reviewedscientific journal that publish original articles based on ownresearch, as well as review articles and case reports in the field ofpharmacy and military medicine, and modern solutions in the fieldof military and civilian healthcare based on the latest national andinternational achievements.Military Pharmacy and Medicine is quarterly interdisciplinaryjournal of Military Centre of Pharmacy and Medical Techniquein Celestynów, Poland, published in English on scientific, socioprofessionaland training issues of Military Pharmacy and Medicine.Journal appears continuously and systematically in printed(primary version) and on-line version since 2008 at: http://military.isl-journals.com/and information contained therein are continuouslyupdated, but not less frequently than quarterly.The editors endorse the principles embodied in the Declaration ofHelsinki and expect that all investigations involving humans will havebeen performed in accordance with these principles. For animal experimentationreported in the journal, it is expected that investigators willhave observed the Interdisciplinary Principles and Guidelines for theUse of Animals in Research, Testing, and Education issued by the NewYork Academy of Sciences Adhoc Committee on Animal Research. Allhuman and animal studies must have been approved by the investigator’sInstitutional review board. It is recommended to enclose a copy ofthat document to a submitted manuscript.Editors Military Pharmacy and Medicine in the daily practice refer tothe guidelines of the Committee on Publications Ethics concerningCode of Conduct and Best Practice Guidelines for Journal Editors(http://publicationethics.org/resources/guidelines).1. Review process and submission rulesEditors consider only submissions in English. Manuscripts are evaluatedon the basis that they present new insights to the investigatedtopic, are likely to contribute to a research progress or change in clinicalpractice or have the desirable teaching/training value. The correctnessensures Editor-in-Chief, Deputy Editor, Section Editors, Statistical Editor,reviewers and Linguistic Editors.The signature of the corresponding author on the letter of submissionsignifies that:1) paper is original and created by you (not copied),2) paper has not been published previously or submitted elsewherefor review and a copyright transfer,3) it is understood that all authors listed on a manuscript haveagreed to its submission.Received manuscripts are first examined by the Military Pharmacyand Medicine editors due to preparation of the manuscript, photographicdocumentation, and all authors consent to publication.Manuscripts with insufficient priority for publication are rejectedpromptly. Incomplete packages or manuscripts not prepared in theadvised style will be sent back to authors without scientific review.The authors are notified with the reference number upon manuscriptregistration at the Editorial Office. The registered manuscriptsare sent to at least two independent experts for scientific evaluation.Competent reviewers designate Editor-in-Chief. Reviewers prepareopinions that contain reasoned recommendations and suggestionsof corrections and additions to content and form of the article.http://military.isl-journals.com/In case of papers written in a foreign language at least one of thereviewers is affiliated to a foreign institution. Reviewed paper andreviewers did not come from the same institution.The author and the reviewer are anonymous to each other accordingto double-blind review policy.Rejection requires two negative reviews. Editor-in-Chief reservesthe right to refuse to print a paper containing the results of studies inwhich ethical principles are not respected according to the Declarationof Helsinki in 1964, Tokyo in 1975 and the recommendationsof the World Health Organization in 1982.Submitted papers are accepted for publication after a two positiveopinion of the independent reviewers, who agreed that thepaper can be published in present form. If the reviewers differin their opinions, or feel that the manuscript should be acceptedonly after the corrections, editors may take a decision to sendpaper to another reviewer in order to settle or return it to theauthors for correction.The final decision on acceptance for publication or to reject belongsto competences of the Editorial Board and is not subject to appeal.Editorial Board decisions do not have to justify.The reviewing process usually takes 3-6 weeks, however Editors cannotguarantee the date of publishing.Military Pharmacy and Medicine publishes an updated list of reviewerson the website, as well as an annual list of reviewers in the last issueof the journal (every year).2. Conflict of interestsAuthors should disclose contribution of individual authors to preparationof manuscript (with a list of their affiliations) in detail, i.e.provide information who is the author of concept, premises, methods,protocol etc.Authors of research articles should disclose at the time of submissionany financial arrangement they may have with a companywhose product figures prominently in the submitted manuscriptor with a company making a competing product. Such informationwill be held in confidence while the paper is under reviewand will not influence the editorial decision, but if the article isaccepted for publication, the editors will usually discuss with theauthors the manner in which such information is to be communicatedto the reader.Because the essence of reviews and editorials is selection and interpretationof the literature, the Military Pharmacy and Medicineexpects that authors of such articles will not have any financial interestin a company (or its competitor) that makes a product discussedin the article.Military Pharmacy and Medicine policy requires that reviewers,associate editors, editors, and senior editors reveal in a letter to theEditor-in-Chief any relationships that they have that could be construedas causing a conflict of interest with regard to a manuscriptunder review. The letter should include a statement of any financialrelationships with commercial companies involved with a productunder study.3. PermissionsMaterials taken from other sources must be accompanied by a writtenstatement from both author and publisher giving permissionto the Military Pharmacy and Medicine for reproduction. Obtain133

© Military Pharmacy and Medicinepermission in writing from at least one author of papers still in press,unpublished data, and personal communications.4. Patients confidentialityChanging the details of patients in order to disguise them is a formof data alteration. However authors of papers are obliged to ensurepatients privacy rights. Only clinically or scientifically importantdata are permitted for publishing. Therefore, if it is possible to identifya patient from a case report, illustration or paper, Military Pharmacyand Medicine Editors ask for a written consent of the patient orhis/her guardian to publish their data, including photograms priorto publication. The description of race, ethnicity or culture of a studysubject should occur only when it is believed to be of strong influenceon the medical condition in the study. When categorizing byrace, ethnicity or culture, the names should be as illustrative as possibleand reflect how these groups were assigned.5. Copyright transferUpon acceptance, authors transfer copyright to the Military Pharmacyand Medicine. Once an article is accepted for publication, theinformation therein is embargoed from reporting by the media untilthe mail date of the issue in which the article appears.Upon acceptance all published manuscripts become the permanentproperty of the Military Centre of Pharmacy and Medical Techniquein Celestynów, Poland as the Publisher of the Military Pharmacy andMedicine, and may not be published elsewhere without written permissionfrom the Military Centre of Pharmacy and Medical Techniquein Celestynów, Poland.The date of acceptance for printing shall be the date of sending thefinal version of the article. Editorial provides one copy printed articlefor the correspondence author.6. DisclaimerEvery effort is made by the Publisher and Editorial Board to see thatno inaccurate or misleading data, opinion or statement appear inthe Military Pharmacy and Medicine. However, they wish to make itclear that the data and opinions appearing in the articles and advertisementsherein are the responsibility of the contributor, sponsoror advertiser concerned. Accordingly, the Publisher and the EditorialBoard accept no liability whatsoever for the consequences ofany such inaccurate of misleading data, opinion or statement. Everyeffort is made to ensure that drug doses and other quantities are presentedaccurately. Nevertheless, readers are advised that methodsand techniques involving drug usage and other treatments describedin this Military Pharmacy and Medicine, should only be followed inconjunction with the drug or treatment manufacturer’s own publishedliterature in the readers own country.7. Qualification criteriafor manuscriptsEditorial Board of Military Pharmacy and Medicine takes underconsideration for publication original articles in experimental andclinical medicine and related disciplines with the understandingthat neither the manuscript nor any part of its essential substance,tables or figures have been published previously in print form orelectronically and are not taken under consideration by any otherpublication or electronic medium. Copies of any closely relatedmanuscripts should be submitted to the Editor along with theEDITORIAL POLICY AND GENERAL INFORMATIONmanuscript that is to be considered by the Military Pharmacy andMedicine. The Editor discourages the submission of more than onearticle dealing with related aspects of the same study.Each submission packet should include the statement signed by thefirst author that the work has not been published previously or submittedelsewhere for review and a copyright transfer.8. Categories of articlesAccepted manuscripts are published in the following journal sections:1) Original articles: reports of previously unpublished results fromscientific experiments conducted by the authors in order toconfirm or refute a clearly identified hypothesis. Most of thearticles published in a given issue will belong to this category.2) Review articles: reports on the current state of knowledgein a given area or field of study, especially current controversies,theoretical and practical approaches to the issues, unresolvedproblems, etc., with carefully selected references to the literature.Such articles are typically commissioned by the editors ofMilitary Pharmacy and Medicine, though an unsolicited reviewarticle may be accepted if it is exceptionally interesting andcarefully prepared.3) Case Reports: detailed description of the diagnosis and/or treatmentof 1-3 individual patients, with particular emphasis on anyatypical or difficult aspects of therapy in this particular case thatmay be of interest to readers.4) Short Communications: brief descriptions of selected clinicalsolutions to particular problems; possibly also new discoveriesnot yet experimentally confirmed.5) Opinion articles: authorial discussions of important issues,controversies, and schools of thought in the area of physiotherapy;also, educational (training) articles.9. Preparation of manuscriptGuidelines for submission in Military Pharmacy and Medicine are inaccordance with: Uniform Requirements for Manuscripts Submittedto Biomedical Journals (N Eng J Med, 1997; 336: 309-15. www.acponline.org/journals/resource/unifreqr.htm).The submitted manuscript should be:1) Original and prepared according to the current spellingand terminology. Sent to editing in electronic form (by e-mailor by regular post on CD/DVD) in one of the following formats:*.doc, *.docx, *.rtf, *.odt, *.sxw, *.sdw.2) Electronic file should require the following format (withoutspaces between last names):••LastNameFirstNameInitial-ArticleTitle i.e.SmithJ-Recent advances in clinical…or in case of multi-authorship submission••(FirstAuthor)LastNameFirstNameInitial_et al-ArticleTitlei.e. SmithJ_et al-Recent advances in clinical…3) Title page should have the following information:••Manuscript full title – 12-point typeface, bold;••Full names of all authors;••Type of article (original, review, case report etc.);••Affiliations of the authors;••Full name, address, phone number, fax number and e-mail of the134 http://military.isl-journals.com/

© Military Pharmacy and Medicine EDITORIAL POLICY AND GENERAL INFORMATIONcorresponding author responsible for manuscript preparation,in the following format:Antoni Penc MD PhD, Department of Radiology, University Hospital,Dobra 22, 01-153 Warsaw, POLAND; phone (+48)227786734,fax: (+48) 227776671; e-mail: antoni.penc@wp.pl;••Summary - no more than 15 lines, single-space;••Key words (5 to 10) or short phrases should be written at thebottom of the page including summary. The use of the itemsincluded in Index Medicus (Medical Subject Headings) isrequired;••Source(s) of support in the form of grants (quote the numberof the grant) equipment, drugs etc;••Statement that neither this manuscript nor one with substantiallysimilar content or research under my (our) authorship has beenpublished or was sent for publication elsewhere.4) Structured Summary: (up to 250 words), consisting of the followingsections: Background and study aim, Material and methods,Results, Conclusions:e) Introduction (or Background): should contain scientificrationale and the aim of the study or (in case of a review)purpose of the article;f) Material and methods: brief description of the study; in the caseof review article - characteristics of the literature; for a case study- a brief description of the patient, the main parameters, etc.g) Results: concisely and reasonably summarize the findingsh) Conclusions: the principal conclusions (in Summary: 1-2)drawn by the authors of the presented results. For review papersthe above-mentioned structure is not required.9) TEXT. The text of the article should be divided to six paragraphslabeled: Introduction (or Background), Material and Methods,Results, Discussion, Conclusions, References. Prior references,if necessary, you can attach Acknowledgements, and at the endof work - Appendix. Each of these sections must be clearlyseparated with the bold title.Where appropriate, depending on the content of the article, youcan use a different layout, however, on condition that the structureof work is clear, transparent and consistent. The editorsreserve the right to request the author(s) to improve the structureof manuscript.10) Introduction (or Background) should give the scientific and/orclinical rationale for researching the given topic, the primaryissues and controversies, an explanation of the aim of the studyand the primary thesis.11) Material and Methods should contain essential informationregarding how the experiment or research was conducted,including the essential characteristics of the experimental andcontrol groups (age, gender), inclusion and exclusion criteria,and the randomization and masking (blinding) method used.The protocol of data acquisition, procedures, investigatedparameters, methods of measurements and apparatus shouldbe described in sufficient detail to allow other scientists toreproduce the results. In the case of published methods, thenames with appropriate references should be given. Referencesand a brief description should be provided for methods thathave been published but are not well known, whereas new orsubstantially modified methods should be described in detail.The rationale for using such new or unknown methods shouldbe discussed, along with a balanced evaluation of these methods,not omitting their limitations. Drugs and other chemicalsshould be precisely identified, including the generic name,dosage, and route of administration.http://military.isl-journals.com/The statistical methods should be described in detail to enableverification of the reported results.Information regarding the patients’ informed consent should beincluded in the text of the article (see above: Patient confi dentiality).Study subjects should be identified only by arbitrarily assignedinitials or numbers. Any information contained in photographs,images, or other illustrations that could serve to reveal theperson’s identity should be thoroughly camouflaged or concealed.The faces of persons appearing in photographs should be maskedor covered with a black band, unless for compelling reasons thisis impossible.12) Results concisely and reasonably summarize the findings inthe form of text, tables and figures arranged in a logical andinternally self-consistent manner. The number of tables andfigures should be limited to those absolutely needed to confirmor refute the thesis. Data given in graphs and tables should not beautomatically repeated in the text. The number of observationsshould be clearly indicated, as well as exclusions or losses toobservation. Any complications that may occur in treatmentor examination should be reported.13) Discussion should deal only with new and/or important aspectsof the results obtained, without repeating in detail data or othermaterial previously presented in Background or Results. TheDiscussion should focus on the theoretical implications and/orpractical consequences of the findings, including suggestionsfor further research. The Discussion should compare the resultsof the present study to those obtained by other investigatorsmentioned in the text.14) Conclusions must be linked with the goals of the study. Newhypotheses with recommendations for further research shouldbe advanced only when fully warranted and explicitly justified.Include recommendations when appropriate. Unqualifiedstatements and conclusions not supported by the data obtainedshould be avoided.15) Acknowledgements list all those who have contributed to theresearch but do not meet the criteria for authorship, such asassistants, technicians, or department heads who provided onlygeneral support. Financial and other material support shouldbe disclosed and acknowledged. References, chosen for theirimportance and accessibility, are numbered consecutively inthe order of their occurrence in the text.References first cited in tables or figure legends must be numberedin such a way as to maintain numerical sequence with the referencescited in the text. The style of references is that of IndexMedicus. When an article has six or fewer authors, all shouldbe listed; when there are seven or more, only the first three arelisted, then “et al.”16) Original papers and review papers may not exceed the standardtypewritten pages 10-20, and case studies – 4 pages, includingreferences, summary, tables and figures.Editors may agree to exceed the number of pages in case of: summariesof habilitation dissertation and the habilitation dissertationon degree of doctor of pharmaceutical and medical sciences.17) One page of manuscript should contain 30 lines, with about 60characters each (approx. 1800 characters per page). The textmust be written in Times New Roman 12-point, double-spaced(except references, tables, captions, etc.), with the left margin,2.5 cm wide, but without the right margin, or the comment. Donot center the title and heading, do not use tabs and blank linesbetween paragraphs or calculations. Use only bold and italic.135

© Military Pharmacy and Medicine18) Tables and illustrations. Number tables consecutively in theorder of their first citation in the text, and supply a brief titlefor each. Give each column a short or abbreviated heading. It isrecommended the simplest possible arrangement of the table,without unnecessary horizontal or vertical rules. Place explanatorymatter in footnotes, not in the heading. The footnotes shouldbe numbered separately, starting with 1 for each table. Explainin footnotes all nonstandard abbreviations that are used in eachtable. Type or print out each table on a separate sheet of paper.Be sure that each table is cited in the text. Tables, Illustrations,Figures, Photographs etc. should be numbered and describedType or print out each Tables, Illustrations, Figures, Photographsetc. on a separate sheet of paper. In the main text shouldbe noted the place of insertion of each Tables, Illustrations, Figures,Photographs etc. The number of tables should be reducedto minimum. Figures (including maps), and photographs areplaced in a separate file(s).If the Figures and Photograph contain text to be translated,the file(s) containing must be editable or author(s) should sendthem in English language.Figures and photographs should be professionally drawn andphotographed; freehand or typewritten lettering is unacceptable.Titles and detailed explanations belong in the legends for illustrations,not on the illustrations themselves. Each figure shouldhave a label pasted on its back indicating the number of the figure,author’s name, and top of the figure. Do not write on the back offigures or scratch or mar them by using paper clips. Do not bendfigures or mount them on cardboard.Figures should be numbered consecutively according to theorder in which they have been first cited in the text. If a figurehas been published, acknowledge the original source and submitwritten permission from the copyright holder to reproducethe material. Permission is required irrespective of authorshipor publisher, except for documents in the public domain. Photographsshould be color or black & white glossy prints with numbersand descriptions on the back, following the pattern: title,authors, number of the photograph, its description. All photographsare printed as standard black and white. You can printphotos in full color, for an additional fee.Photomicrographs should have internal scale markers. Symbols,arrows, or letters used in photomicrographs should contrast withthe background. If photographs of people are used, either thesubjects must not be identifiable or their pictures must be accompaniedby written permission to use the photograph.19) References. In all cases correct punctuation should be used todivide the parts of the reference to the cited position. Becauseof the possibility of modifications or amendments, referencesto materials from Internet should include the file viewing ordownloading date. If there are more than three authors, thenames of the first three should be listed and then „et al.“ shouldbe used. Abbreviated titles of journals cited should be consistentwith MEDLINE.Papers published in journals:12. Pui CH, Behm FG, Raimondi SC et al: Secondary acutemyeloid leukemia in children treated for acute lymphoid leukemia.N Eng J Med, 1989; 321(3): 136–42.Book chapters:3. Kowalczyk JR: Cytogenetics of secondary leukemias.In: Becher R, Sandberg AA, Schmidt CG (eds.): Chromosomesin Hematology. W. Zuckschwerdt Verlag, Munchen,1986,pp. 125–45.Electronic materials (Internet):6. Martin JM: A software for the description of workplacesin the PRS system. http://www.matforsk.no/ola/fisher.htm(accessed 29.08.2002).EDITORIAL POLICY AND GENERAL INFORMATIONAvoid using abstracts or review papers as references. Unpublishedobservations and personal communications cannot be usedas references. If essential, such material may be incorporated inthe appropriate place in the text.20) Units of Measurement. Measurements of length, height, weight,and volume should be reported in metric units (meter, kilogram,or liter) or their decimal multiples. Temperatures should begiven in degrees Celsius. Blood pressures should be given inmillimeters of mercury.All hematological and clinical chemistry measurements should bereported in the metric system in terms of the International Systemof Units (SI). Alternative or non-SI units should be addedin parenthesis.Identify statistical measures of variations such as standard deviationand standard error of the mean. If you use data from another publishedor unpublished source, obtain permission and acknowledgethem fully21) Abbreviations and Symbols. Use only standard abbreviations.Avoid abbreviations in the title and abstract. The full term forwhich an abbreviation stands should precede its first use in thetext unless it is a standard unit of measurement.10. Sending the manuscriptto the journalAuthors are requested to submit the manuscript in electronic formon e-mails: remirad@o2.pl orhttp://military.isl-journals.com/index.php?/authors/login/Manuscripts must be accompanied by a covering letter signed by allco-authors. This must include:1) information on prior or duplicate publication or submission elsewhereof any part of the work as defined earlier in this document;2) disclose contribution of individual authors to preparation of apublication (with a list of their affiliations); editors make an effortto prevent cases of misconduct (ghostwriting, guest authorship);3) a statement of financial or other relationships that might leadto a conflict of interest (see below);4) a statement that the manuscript has been read and approved byall the authors, that the requirements for authorship as statedearlier in this document have been met.The manuscript must be accompanied by copies of any permission toreproduce published material, to use illustrations or report informationabout identifiable people, or to name people for their contributions.Editors consider the above conditions to be fulfilled if the signatureof the first author was made.11. Final remarks:1)The editors reserve the right to correction of grammatical, stylisticdefects or shortening paper without the agreement with authors.The paper does not qualify for the print may be returned at therequest of the author.2)Translations from Polish into English are made by the publisher.Individual translation is allowed. Then the author(s) shouldclearly indicate that the paper require or not language correction.3)Authors, members of the Scientific Board, members of theEditorial Board, reviewers and libraries of medical universitiesreceive one copy of the Military Pharmacy and Medicine. Copyin PDF format is allowed.136 http://military.isl-journals.com/

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