Introduction In order of responsible approaching to all the challenges of modern nursing, the nurse accepts responsibility and commitment in providing health care within the legal domain of nursing practice. Nursing is facing a complex request for identification and elimination of the patient's problems involving ethical approach, knowledge, skills and abilities. In their work, nurses daily encounter with resuscitation of patients, where they are required by conscience and commitment to save every human life. Cardiac arrest is a condition characterized by extremely high mortality. Especially important topic relates to nurses employed in the field of primary health care, who work in isolated clinics in rural areas, where they are often the only health workers and must themselves make a decision on the initiation and implementation of cardiopulmonary resuscitation. Through long history, cardiopulmonary resuscitation passed through different phases that were associated with technological and scientific development Abstract *1,2Zlatko Ciric, 3,4Dejan Zivanovic, 2,5Natasa Stojakovic

Background: Metabolic capacity of gut microflora is huge and this “microb” organ can be considered as second biggest metabolic organ in body. The potential for an antibiotic to influence gut microflora is related to its spectrum of activity, pharmacokinetics, dosage and length of administration. In terms of pharmacokinetics, the rate of intestinal absorption plays a fundamental role. Apart from basic physiological functions, bile acids and their analogues are recognized as transport promoters for other substances, in potentiating their action. The aim of this study was to demonstrate potential protective effect of monoketocholic bile acid on rat intestinal microflora from oral ampicillin. Materials, Methods & Results: Eighteen Wistar rats were divided into three groups (n = 6). The experimental protocol was approved by Ethics Committee on Animal Use of the University Novi Sad. All animals received 10 mL/kg of body weight of drugs solutions per os by oral intubations. The animals have been treated twice daily for three days, with saline, ampicillin 500 mg/kg and ampicillin 500 mg/kg + monoketocholic bile acid (MKH) 4 mg/kg. The fecal pellets were collected twice, before and after the treatment was completed. Within 2 h of collection, samples of whole pellets were processed microbiologically. Weighed portions of feces were suspended 1:10 in sterile 0.9% NaCl and further diluted with same solutions up to 1: 10 13 . The number of colony forming units (CFU) was determined by direct counting. Only the plates containing 30 to 300 CFU were considered as valid. The ampicillin treated group, showed significant reduction of CFU number compared to value before treatment under aerobic (P = 0.019) and anaerobic (P = 0.00) conditions. Concomitant use of ampicillin and MKH did not show statisticaly significant reduction ( P > 0.05) of CFU number compared to value before treatment in both cultivation conditions. There is significant reduction of CFU number ( P = 0.02) only in group treated with ampicillin comparing to control group under the aerobic condition. Statistical analysis was performed by single test ANOVA and Kruskal- Wallis test with Monte Carlo exact test to test significant differences in CFU reduction between groups. Paired two-tailed t-test was performed on the log-transformed data of the CFU/g fecal sample to test for significant differences between counts before and after treatments inside the group. Discussion: Oral antibiotic applications can change the composition of normal gut microflora. Modification of normal mi croflora can change metabolism of many compounds. Longer local retention of ampicillin in the gut, due to poor absorption of antibiotic has led to a significant reduction in the number of intestinal microorganisms. Although the fecal flora does not exactly represent the gut flora, comparison of number of CFU from feces specimen before and after antibiotic treatment indirectly reflects the effect of the antibiotic on the bacteria in the gut. Co-administration of ampicillin and MKH, due to promoting effect of bile acid on to absorption of ampicillin, led to less disruption of CFU than in ampicillin group. Based on these results, it is concluded that concomitant use of ampicillin and MKH, could be useful for reducing the harmful effects of ampicillin on the intestinal flora . These results are consistent with the results obtained in pharmacokinetics study with the same substances.

Dear Editor, With the number of percutaneous coronary interventions (PCIs) on the rise, it is expected that there will be a corresponding growth in population of patients with prior PCI referred to coronary artery bypass grafting (CABG) as a result of long-term PCI failure, incomplete revascularization, or coronary artery disease progression. The prevalent position of the interventional cardiologists of: ‘‘subsequent CABG may be successfully performed in any patient with a history of previous PCI’’ is now being seriously challenged. Furthermore, results of several studies that investigated the impact of previous PCI on subsequent CABG were found to be conflicting. For this reason, we read with great interest the article by Niclauss et al. regarding the influence of prior PCI on subsequent CABG. There are only a few studies reporting onmidor long-term results following surgical revascularization in patients with prior PCI, and from that point of view the article by Niclauss et al. is indeed a very fine contribution. This study produced another very important conclusion—there is no difference in terms of mortality depending on prior PCI status. However, a cautionary warning was identified in that particular study: the proportion of patients who underwent isolated percutaneous transluminal angioplasty (PTCA)—20% in PCI prior CABG group—looks to be far too big for contemporary clinical practice in our view. Having in mind different pathophysiological mechanisms responsible for PTCA and PCI failure, we believe that such a large number of patientsmight, in fact, skew the results of the study. We, therefore, think that excluding the subgroup of patients would yield results that would be more representative of a contemporary practice. In Table 1, it is indicated that a proportion of patients with prior myocardial infarction (MI) is very similar between the groups (40% vs. 44%, p1⁄4 0.07). Does this mean that the patients with MI were not treated with PCI in large number? The report did not appear to indicate the number of patients having previous MI treated with PCI that were subsequently referred to CABG. For the purpose of analysis, it would be useful to see in what percentage was the artery, already treated with stent, revascularized surgically. Another factor worthy of attention is the number of multiple PCIs and its influence on CABG. Based on our clinical practice, we know that cardiologists are likely to be very persistent in their attempts to percutaneously revascularize the artery. Table 2 of Niclauss et al. paper counts 22.3% (89) prior-PCI patients taking clopidogrel which seems quite low. We seek explanation about how long the patients took the drug following PCI. Again, 77.7% of patients with previous PCI were merged with those not submitted to PCI when the impact of active double anti-platelet therapy was investigated. We believe that conclusions would be more accurate (meaningful) if only the original groups were considered. Careful decision-making in the setting of multivessel disease is mandatory. Obviously, many risk factors (patient related, procedure related, drug related, coronary artery anatomy, and pathology) may influence the success or failure of specific procedures, thus emphasizing the need for adequate patient selection according to corresponding procedure type. In order to gain meaningful insight about the relation between PCI and subsequent CABG, more contemporary studies including a larger proportion of patients treated with drug eluting stents and/or biodegradable stents are highly warranted. Conflict of interest: The authors acknowledge no conflict of interest in the submission.

INTRODUCTION Statins have similar side effects that do not always occur at the same rate among the various statins. We present a case of simvastatin-induced muscle toxicity that disappeared when pravastatin was substituted for the original drug. CASE OUTLINE A 74-year-old male, a nonsmoker, complained of severe nocturnal leg cramps. The patient also complained that similar painful cramping occurred when he walked rapidly or jogged. Because some components of his lipid panel exceeded the'desirable' range, and as he had a history of myocardial infarction, his family physician prescribed simvastatin (40 mg/day). The patient had taken this medication for the past eight years. The painful nocturnal episodes started two years ago and affected either one or the other leg. Four months ago we discontinued his simvastatin and prescribed pravastatin (80 mg/day). At a follow-up visit six weeks later, the patient reported that his leg pains at night and the pain experienced after brisk walking had disappeared. Four months after the substitution of pravastatin for simvastatin, the patient reported that his complete lack of symptoms had continued. CONCLUSION These painful muscle cramps were probably caused by an inadequate vascular supply to the calf and foot muscles. Perhaps a combination of advanced age and atherosclerotic changes created a predisposition for the simvastatin-induced leg cramps. Pravastatin differs from simvastatin in several ways.l It is not metabolized by cytochrome P450 (CYP) 3A4 oxidases, and thus is not influenced by CYP 3A4 inhibitors like simvastatin. Also, simvastatin is associated with single-nucleotide polymorphisms located within the SLCO1B1 gene on the chromosome 12 and established myopathy, while pravastatin lacks this association. These differences may contribute to increased tolerance to pravastatin in this particular case.

Smokers have an increased risk of perioperative and postoperative complications, including a higher incidence of airway and respiratory, cardiovascular events, and impaired wound healing. This brief review will remind anesthesiologist and surgeons that their preoperative smoking intervention for smoking cessation can be effective in decreasing the incidence of complications. Preoperative smoking intervention, even if it is both brief and intensive, may help to decrease this risk. The surgical event is the important ‘teachable moment’ that could translate, with proper smoking intervention, into permanent smoking cessation.

The aims of this study are the isolation and identification of possible bacteriological agents in respiratory infections of calves and the optimization of a diagnostic protocol to identify Arcanobacterium haemolyticum. Lesions of lungs from calves with pneumonia were examined. Cultural, morphological and conventional biochemical testing were done. The investigation was complemented by the double CAMP test. Five strains of Arcanobacterium haemolyticum in pure culture were found. The presence of Arcanobacterium haemolyticum in the lungs of calves with pneumonia was established and, consequently, more attention should be paid to this species in everyday laboratory work. The cultural similarity of Arcanobacterium haemolyticum to common bacteria like beta-hemolytic Streptococcus spp. and Arcanobacterium pyogenes is probably responsible for rare reports on the isolation of Arcanobacterium haemolyticum in veterinary microbiology. Our results indicate that Arcanobacterium haemolyticum could be or is the etiological agent of pneumonia. Therefore, we suggest the diagnostic protocol available for routine work in most microbiological laboratories. [Projekat Ministarstva nauke Republike Srbije, br. 41012]

During the last several years many authors have found that the European System for Cardiac Operative Risk Evaluation is useful in the prediction of not only postoperative mortality but also of the length of stay in the intensive care unit, complication rate and overall treatment expenses. This study included 329 patients who had undergone isolated surgical myocardial revascularization at our Department during the period from January 1st to June 6th, 2008. For the operative risk evaluation, the additive European System for Cardiac Operative Risk Evaluaion was used. In group I (low risk 0-2%) there were 144 patients (43.7%), whereas group II (medium risk 3-5%) and group III (high risk > or = 6%) included 141 (42.8%) and 44 (13.4%) patients, respectively. The length of stay in the intensive care unit was 25.56, 32.43 and 49.59 hours for groups I, II and III, respectively. The difference in the mean length of stay in the intensive care unit between the groups was highly statistically significant (p < 0.001) with a positive correlation (R = 0.193; p < 0.001). There is a positive correlation in patients who had undergone surgical myocardial revascularization in terms of operative risk expressed by the additive European System for Cardiac Operative Risk Evaluation and length of stay in the intensive care unit, total intubation period and development of early postoperative complications.

Statins, such as simvastatin, lower circulating cholesterol levels and are widely prescribed for the treatment of hypercholesterolaemia. Several studies have shown unexpected effects of statins on inflammation. We studied the anti-inflammatory effect of simvastatin using a standard model of an acute local inflammation, the carrageenan-induced footpad oedema. Experimental groups (n = 6-8) were given simvastatin in a dose range 5-30 mg/kg, indomethacin 1-8 mg/kg and methylcellulose (control) per os. Footpad volume was measured with a plethysmograph and compared with the pre-injection volume of the same paw. Swelling (in microlitres) was then calculated, and in drug-treated animals, per cent inhibition was derived through comparison with the control group. Histopathological examination of the skin biopsies was performed to examine severity of paw skin lesions and to confirm the simvastatin-induced inhibition of acute inflammation. Both simvastatin and indomethacin administered orally, 1 hr before carrageenan injection, significantly reduced the extent of footpad oedema. Indomethacin dose-dependently blocked the swelling; the maximal effect was obtained with 8 mg/kg by 48.3% (P < 0.05). Simvastatin produced a comparable anti-inflammatory activity at a dose of 5 mg/kg (32%), while 10 and 30 mg/kg caused a 47.6% and 51.7% reduction, respectively, with the maximal effect observed at 20 mg/kg by 57.2% (P < 0.05). The comparison of the ED(50) of these agents on molar basis showed equipotent anti-inflammatory activity. Histopathological examination of the footpad skin biopsies revealed that simvastatin, dose-dependently and comparablly to indomethacin, reduced polymorphonuclear leucocyte infiltration. These data support the hypothesis that simvastatin has an acute anti-inflammatory activity.

The effect of simvastatin applied in a short-term pretreatment on proinflammatory cytokines production in acute systemic inflammation induced by endotoxin - lipopolysaccharide (LPS) in rats was investigated. Both LPS and simvastatin doses were established in separate experiments in which increasing doses of both compounds were given to obtain the LD(50) LPS and the maximally protective dose of simvastatin against LD(50) LPS. To determine the anti-inflammatory effect, simvastatin was given orally for 5 days, followed by a single intraperitoneal non-lethal dose of LPS (0.25 LD(50)). Plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 were measured by enzyme-linked immunosorbent assay. The acute i.p. LD(50) LPS amounted to 22.15 mg/kg. Simvastatin of 20 mg/kg p.o. was maximally protective against LD(50) LPS, and this dose was used for studying its effects on LPS-induced cytokines production. Cytokines concentrations were significantly increased upon challenge of non-lethal dose of LPS. The peak levels of TNF-alpha and IL-1beta were significantly suppressed by simvastatin, compared to control rats only treated with dimethylsulfoxide before LPS. In contrast, simvastatin did not affect IL-6 levels at all timepoints. Simvastatin pretreatment given orally produced acute anti-inflammatory effects by inhibiting TNF-alpha and IL-1beta, but no IL-6 production.

Sažetak. Infekcije tmdnice su relativno česte, tako da je često i propisivanje antibiotika и trudnoći. Vrsta antibiotika, doza, trajanje, način i učestalost primjene zavise od uzročnika i težine bolesti. U Sjedinjenim Američkim Državama, prema Upravi za hranu i lijekove (engl., Food and Drug Administration, FDA) svi lijekovi, prema riziku za oštećenje ploda, svrstavaju se и 5 grupa (А, В, C, D, X). Najmanji rizik imaju lijekovi iz grupe A i B, a najveći iz grupe X. Cilj rada je bio da se ispita učestalost primjene antibiotika kod trudnica, koje su najčešće indikacije za njihovu primjenu, koji se antibiotici najčešće koriste i и koju grupu rizika po plod spadaju, te koliko je antibiotska terapija trajala. ® Studija je obuhvatila 694 trudnice. Ispitivanje je provedeno tokom 2004. i 2005. godine. Podaci su prikupljeni modifikovanim upitnikom za trudnice Svjetske zdravstvene organizacije, originalno urađenom na Institutu za farmakološka istraživanja “Mario Negri ”, Milano, ltalija. U toku trudnoće, lijekove je uzimalo 574 (82,71%) žene. U prosjeku, uzimano je 2,84 lijeka po trudnici. Najčešće su korišćeni preparati željeza (69,9%) i vitamini (56,1%), a slijede sistemski antibiotici (33,9%), antimikotici u obliku vaginaleta (22,3%), simpatikomimetici za spriječavanje prijevremenog porođaja (22,0%), polni hormoni (progesteron) (13,9%), te benzodiazepini (12,0%>). Od sistemskih antibiotika najčešće su korišćeni beta laktamski antibiotici (penicilini i cefalosporini, FDA grupa B). Najčešće indikacije za terapiju sistemskim antibioticima su bile: infekcije urinarnog trakta, a zatim respiratornog. Utvrđeno je da su antibiotici primjenjivani i kod virusnih infekcija uz opravdanje da se trudnice zaštite od bakterijske superinfekcije. Oko 3% trudnica bilo je na hroničnoj terapiji, koja je započeta prije i trajala je tokom čitave trudnoće (epilepsija, oboljenja štitne žlijezde, i slično). Antibiotike za sistemsku primjenu je koristila treéina trudnica, a najčešće su korisćeni beta laktamski antibiotici, amoksicilin i cefaleksin. Antibiotici su najčešće korišćeni za liječenje infekcija urinarnog i respiratornog trakta. Kod veéine trudnica, liječenje infekcija bilo je neodgovarajuée.

INTRODUCTION Using the Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) methodology, we analyzed utilization of prescription-only drugs in Banja Luka region in 2000-2001. MATERIAL AND METHODS A retrospective study on drug utilization, according to ATC classification, was conducted on the basis of data received from Central City Pharmacy Banja Luka, and results were presented in terms of DDD/1000 inhabitants/day. RESULTS Pharmaco-epidemiological analysis showed that the list of 20 most frequently prescribed drugs in 2000 included 8 cardiovascular drugs and 6 anti-infective drugs. In 2001, 20 most frequently prescribed drugs, included 9 cardiovascular drugs, and 4 anti-infective drugs. Regarding anti-infective agents, the most frequently prescribed antibiotics were amoxicillin, doxycyline, co-trimoxazole and gentamicin. The most frequently prescribed drug in 2000 was diazepam (5.33 DDD/1000 inhabitants/day). The use of this drug significantly increased in 2001 (7.95 DDD/1000 inhabitants/day). DISCUSSION AND CONCLUSION Based on total analysis, it can be concluded that the positive drug list, defined by the Health Insurance Fund, significantly affected the drug utilization profile, but some drugs are considered to be irrationally prescribed.

Using ATC/DDD methodology, we analyzed antibiotic utilization in the Clinical Centre of Banja Luka, one of the largest clinical centres in Bosnia and Herzegovina, during the war and postwar period (1994-2000), as well as the role of drug donations on doctors' prescribing decisions. The retrospective analysis of antibiotic utilization (group J according to the Anatomical Therapeutical Chemical - ATC classification) was based upon the data provided from the hospital computer centre and calculated as the number of defined daily doses (DDD) per 100 bed days. The pharmacoepidemiological analysis showed that the total use of antibiotics changed markedly; in the war year of 1994, as well as in 1998, antibiotics were the second most frequently used group of drugs (19.7% and 14.1% of total drug utilization respectively), while in the following years antibiotics were considerably less used. These dynamics were significantly influenced by drug donations, the percentage of which in the overall antibiotic supply in 1996 was 91.5%, while in 1999 and in 2000 it decreased considerably to 46.8% and 45.6%, respectively. The most widely prescribed antibiotics were penicillins, aminoglycosides, sulphonamides and tetracyclines. Among these, the aminopenicillins, co-trimoxazole, gentamicin and tetracyclines were mainly (70-100%) supplied as a drug donations. However, macrolides, cephalosporins and quinolones were less used due to fact that they were considerably less often delivered through drug donations. It can be concluded that the drug donations had a significant impact on prescribing practice and the rational use of antibiotics in the Clinical Centre studied.