Showing papers in "Acta medica Croatica : c̆asopis Hravatske akademije medicinskih znanosti in 2004"

Biochemical markers in acute coronary syndrome

Abstract: For many years, cardiac markers have been used to assist cardiologists in the diagnosis and management of patients with cardiovascular disease. At first, enzyme activities of aspartate aminotransferase, lactate dehydrogenase and creatine kinase have been used in diagnosing patients with chest pain in order to differentiate those with acute myocardial infarction. In the field of cardiac markers, emphasis is currently put on the use of protein markers such as myoglobin, and cardiac troponin T or I. Troponins are very highly cardiac specific and their concentration in blood increase only from four to six hours after the onset of chest pain. Today we obligatorily use two markers, the first being the early one (myoglobin, isoform of creatine kinase), which is very sensitive and shows up in the circulation one to two hours after myocardial damage. Confirmation of myocardial damage can be obtained by definite markers (troponin I or T), which are highly specific of myocardial damage.

Systemic fungal infections in immunocompromised patients

Abstract: Opportunistic fungal infections are becoming more frequent complications during cancer therapy, after organ transplantation and in AIDS infections, especially after better control of bacterial infections in immunocompromised patients. Periods of prolonged neutropenia with neutrophil count less than 0.5 x 10(9)/L longer than 7 days, are the most important risk factors for the development of systemic fungal infections. Especially susceptible are the patients during treatment of acute leukemia, or after bone marrow transplantation. The most frequent causing agents of systemic fungal infections are Candida and Aspergillus species, than Cryptococcus neoformans and Mucor. Some other unusual species such Fusarium, Trichosporon, non-albicans Candida species of Candida are becoming more frequent, and is frequently resistant to conventional therapy. The difficulties in early and precise diagnosis of fungal infections, and the lack of adequate and efficient drugs are responsible for the high mortality of immunocompromised patients, even in potentially curable diseases. The recognition of risk factors, introduction of prophylactic measures, application of empirical antifungal therapy, are the procedures for the reduction of morbidity and mortality of invasive fungal infections. Fluconazole administration in prevention of systemic fungal infections, has become the standard approach, especially after bone marrow transplantation, while the oral itraconazole solution, has even more extended activity. Fluconazole appears successful also in the treatment of systemic Candidiasis. Conventional amphotericin-B is still the "gold standard" in the treatment of fungal infections. The new lipid formulations of amphotericin-B, intravenous itraconazole, has an identical efficacy, but are less toxic than conventional amphotericin-B. Several new promising agents are in the stage of clinical investigation like voriconazole, caspofungin, mycafungin and some other.

Antioxidative activity of propolis from Dalmatia (Croatia)

Abstract: AIM The aim of this study was to determine the antioxidative activity of propolis from ecologically clean parts of Dalmatia. METHODS Phenol concentration in ethanolic propolis extracts was determined by Folin-Ciocalteu reagent using gallic acid as the standard. Flavonoid phenolic compounds were analyzed after precipitation with formaldehyde. The residual non-flavonoid phenolics were also determined by Folin-Ciocalteu method. By determining the change of peroxide number (PN), of tiobarbiture acid reactive species (TBARS), and of DPPH-radical activity, antioxidative efficiency of propolis was tested and compared with well known and widely used synthetic antioxidants. Values of PN and TBARS were determined at 60 degrees C in samples of trigyceride substrate (lard) without and with the addition of antioxidants. Compared was the efficiency of three antioxidants: propolis (alcoholic extract), vitamin E, and (+)-catechin in a concentration of 1%. PN was monitored during 50 days. By the method of Sedlacek, TBARS were measured during 30 days. Antioxidative activity of propolis extract was also measured in terms of hydrogen donating ability using stable radical alpha,alpha-diphenyl-beta-picril hidrazyl (DPPH*) and compared with commercial synthetic antioxidants of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and (+)-cathecin. Inhibition degree of DPPH* was calculated by the formula of Yen and Duh. RESULTS Total phenol content, expressed as gallic acid, in propolis extracts varied from 75.2 to 90.2 g/kg propolis. The proportion of flavonoids in total phenols ranged from 62% to 65%. Values of TBARS were not increased only in samples with added propolis. The inhibition of DPPH-radical by propolis extracts ranged from 93% to 96%, by catechin 95%, by BHT 49%, and by BHA 64%. Compared to BHT and BHA, propolis extracts showed greater reducing activity against DPPH-radical. DISCUSSION The chemical composition of propolis, and thus its biological activity depend on the plant from which it has been collected, and on the macro- and microclimatic conditions. Many compounds in propolis exert antioxidative activity. A belief was expressed that the biological activity of propolis is very probably based mostly on its antioxidative efficiency. Dalmatian propolis showed high efficiency in the prevention of oxidative processes. This could be explained by the high proportion of polyphenol constituents, especially flavonoids. A very low and equal degree of increase of PN, as a measure of oxidative processes, was noticed in the samples of triglyceride substrate with the addition of propolis and (+)-catechin. The greatest rise of TBARS was measured in the samples of pure lard. There was no increase of TBARS only in the samples with added propolis. Propolis and (+)-catechin showed great efficiency in the inhibition of DPPH-radical, greater than BHT and BHA, which are widely used in food industry. CONCLUSION The results indicate that Dalmatian propolis could be an efficient protective agent against oxidative processes in food. The high antioxidative activity of propolis, its natural origin, and present knowledge about its biological properties, make it a very promising nutritional additive for human diet.

[Mechanisms of resistance in Enterobacteriaceae towards beta-lactamase antibiotics].

Abstract: Except for Salmonella spp., all Enterobacteriaceae produce intrinsic chromosomal encoded beta-lactamases which, beside their physiologic role in cell-wall synthesis and natural beta-lactam protection, are responsible for intrinsic resistance of individual species among Enterobacteriaceae. E. coli and Shigella spp. produce a small amount of AmpC beta-lactamases and are susceptible to ampicillin and other beta-lactam antibiotic agents. Enterobacter spp, C. freundii, Serratia spp., M. morganii, P. stuarti and P. rettgeri produce small amounts of inducible AmpC beta-lactamases which are not inhibited by beta-lactamases inhibitor, causing intrinsic resistance to ampicillin, co-amoxiclav and first-generation cephalosporins. K. pneumoniae produces small amounts of SHV-1 beta-lactamases, and K. oxytoca chromosomal K1 beta-lactamase, causing resistance to ampicillin, carbencillin, ticarcillin and attenuated zone of inhibition to piperacillin, compared to piperacillin with tazobactam. They are susceptible to beta-lactamase inhibitors. Whereas P. mirabilis shows a minor chromosomal expression of beta-lactamases, P. vulgaris produces chromosomal beta-lactamases of class A (cefuroximases), causing resistance to ampicillin, ticarcillin, and first- and second-generation cephalosporins. Antibiotics have caused the appearance of acquired or secondary beta-lactamases, with the sole function of protecting bacteria from antibiotics. The production of broad-spectrum beta-lactamases (TEM-1, TEM-2, SHV-1, OXA-1) results in resistance to ampicillin, ticarcillin, first-generation cephalosporins and piperacillin. A high level of beta-lactamases leads to resistance to their inhibitors. The plasmid-mediated extended-spectrum beta-lactamases (ESBLs) are of increasing concern. Most are mutants of classic TEM- and SHV-beta-lactamases types. Unlike these parent enzymes, ESBLs hydrolyze oxymino-cephalosporins such as cefuroxime, cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefpirome and cefepime, aztreonam, as well as penicillins and other cephalosporins, except for cephamycin (cefoxitin and cefotetan). They are inhibited by beta-lactamase inhibitors. AmpC beta-lactamases are chromosomal and inducible in most Enterobacter spp., C. freundii, Serratia spp., M. morganii and Providentia spp. They are resistant to almost all penicillins and cephalosporins, to beta-lactamase inhibitors and aztreonam, and are susceptible to cefepime and carbapenems as well. Plasmid-mediated AmpC beta-lactamases have arisen through the transfer of chromosomal genes for the inducible AmpC beta-lactamase onto plasmids. All plasmid-mediated AmpC beta-lactamases have similar substrate profiles to the parental enzymes from which they appear to be derived. With one exception, plasmid-mediated AmpCs differ from chromosomal AmpCs in being uninducible. The National Committee for Clinical Laboratory Standards (NCCLS) has issued recommendations for ESBL screening and confirmation for isolates of E. coli, K. pneumoniae and K. oxytoca. No NCCLS recommendations exist for ESBLs detection and reporting for other organisms or for detecting plasmid-mediated AmpC beta-lactamases. High-level expression of AmpC may prevent recognition of an ESBL in species that produce a chromosomally encoded inducible AmpC beta-lactamase. AmpC-inducible species (e. g. Enterobacter spp. and C. freundii) can be recognized by cefoxitin/cefotaxime disk antagonism tests. Since clinical laboratories are first to encounter bacteria with new forms of antibiotic resistance, they need appropriate tools to recognize these bacteria, including trained staff with sufficient time and equipment to follow up important observations. Because bacterial pathogenes are constantly changing, training must be an ongoing process.

Congenital diaphragmatic hernia in older children

Abstract: The incidence of congenital diaphragmatic hernia (CDH) is about 4.8/10,000 live births. Its typical clinical presentation is respiratory distress occurring immediately after birth or in the first few hours or days of a child's life. It is characterized by a high mortality rate. Exceptionally, CDH can occur at an older age, its symptoms then frequently reflecting gastrointestinal obstruction or mild respiratory symptoms. In such cases CDH presents a far more complex diagnostic problem. The paper presents the cases of two girls without typical symptomatology, aged 5.5 and 10 years, in whom CDH was detected incidentally upon thorough physical examination and chest x-rays. Further radiographic evaluation, which included barium contrast study and spiral computed tomography, confirmed the suspicion of a left-sided posterolateral diaphragmatic hernia with associated intestinal malrotation. Surgical intervention conclusively confirmed a diaphragmatic defect at the site of Bochdalek's foramen in both cases. The vital capacity of the older girl, which was low before the surgery (VC 1.66 L; 69% of predicted), was significantly increased a month after the surgical treatment (VC 2.25 L; 92% of predicted). The generally expressed view that the clinical onset of CDH is rare after the neonatal period seems to be erroneous. Some papers report on the clinical presentation of CDH after the neonatal period in as many as 13%-14% of infants and young children suffering from CDH. Infants and young children with a delayed clinical occurrence of CDH can present with respiratory or gastrointestinal symptomatology. Children presenting with gastrointestinal symptoms have been shown to be significantly older than those presenting with respiratory symptoms. In older children and adolescents, the symptoms and signs of CDH, which include acute hernial incarceration, nausea, recurrent vomiting, diarrhea, obstipation, acute gastric dilatation, subcostal pain, failure to thrive and recurrent chest infections, habitually present a significant diagnostic problem. Diagnostic errors are mainly due to the fact that the possibility of CDH in that age is totally neglected. The most recurrent diagnostic misinterpretations in such cases are pneumonia or massive pleuropneumonia, empyema, pneumothorax, lung cysts and bullae, and gastric volvulus. Thus, whenever a child presents with uncommon respiratory or gastrointestinal symptoms and an anomalous chest x-ray, a differential diagnosis of CDH should be considered. Otherwise, an accurate diagnosis in both young and older children will most probably be only reached at autopsy. In conclusion, the presented cases corroborate the finding that CDH in older children may present with scarce symptoms, mostly gastrointestinal, or may be altogether asymptomatic and unrecognized until as late as adolescence. However, when a diagnosis of CDH has been established, albeit asymptomatic, it must be promptly treated surgically in order to prevent complications, such as strangulation or bowel perforation, and thus avert a potentially fatal outcome. The size itself of the herniac foramen is unlikely to be a determining factor at the time of clinical presentation of CDH. Surgical occlusion of CDH may in older children result in an improved vital capacity, as such cases are rarely associated with major pulmonary hypoplasia. Complications resulting from surgical treatment of CDH in older children are more likely to occur in the gastrointestinal system, as a consequence of the associated bowel malrotation and inadequate bowel fixation. Finally, these two cases corroborate the diagnostic value of accurate history taking and thorough physical examination.

[Some epidemiologic characteristics of foodborne intoxications in Croatia during the 1992-2001 period].

Abstract: U radu su opisane epidemioloske osobitosti alimentarnih toksoinfekcija zabilježenih u Hrvatskoj u razdoblju 1992 - 2001. godine. promatrane su epidemioloske osobitosti otrovanja hranom izazvanih salmonelama, stafilokoknog otrovanja hranom, botulizma, otrovanja hranom izazvanog Clostridium perfringens, histaminskog otrovanja hranom te otrovanja hranom izazvanih drugim uzrocnicima u prvom redu uvjetno patogenim bakterijama. U promatranom desetogodisnjem razdoblju zabilježeno je ukupno 87.782 oboljelih od cega se 45.721 (52, 1%) odnosi na otrovanja hranom uzrokovana salmonelama, dok se na skupinu oboljelih od alimentarnih toksoinfekcija druge etiologije odnosi ostatak od 42.061 oboljelih (47, 9%). Bolest se javlja tijekom cijele godine ali se najveci broj oboljelih bilježi tijekom ljetnih mjeseci. U promatranom razdoblju zabilježeno je ukupno 480 epidemija alimentarnih toksoinfekcija sa 10.567 oboljelih od cega se 405 epidemija (84, 4%) sa 8.476 oboljelih (80, 2%) odnosi na salmoneloze. Od uzrocnika epidemija salmoneloza na prvom je mjestu Salmonella enteritidis koja je dokazano uzrokovala 345 epidemija. Od hrane koja je poslužila kao vehikulum u salmoneloznom otrovanju hranom na prvom mjestu su kolaci (40, 1%). Sladoled je rizican za stafilokokno otrovanje hranom, a salata od kuhanog graha za otrovanje hranom uzrokovano Clostridium perfringens. Glede botulizma, u Hrvatskoj je najrizicnija hrana prsut koji je inkriminiran u sedam od devet epidemija. Histaminsko otrovanje hranom zabilježeno u cetiri epidemije, nastalo je nakon konzumacije ribe ili ribljih prerađevina. S obzirom na mjesto nastajanja, najveci je broj epidemija salmoneloznog otrovanja hranom zabilježen u obiteljima - 149 (36, 8%), na drugom su mjestu slasticarnice sa 47 epidemija (11, 6%) koje su ujedno i najvažnije mjesto izbijanja stafilokoknih epidemija (40%=.

[Bone histology in postmenopausal osteoporosis--variations in cellular activity].

Abstract: AIM Modern understanding of the etiology of postmenopausal osteoporosis is based on the imbalance between bone resorption and formation due to estrogen deficiency, which may take several forms and combinations of decreased and/or increased activity of both or one cell type. Studies of postmenopausal osteoporosis have pointed to the existence of heterogeneity in the remodeling imbalance. Bone histology analyzed in a group of women with established postmenopausal osteoporosis undergoing bone biopsy is part of the diagnostic procedure. Data were compared and grouped according to the published histomorphometric classification of postmenopausal osteoporosis. METHODS The study included 43 postmenopausal women aged 44-71 years with osteoporosis established by densitometry of the lumbar spine and hip. Secondary causes of osteoporosis were ruled out. Full thickness transiliacai bone biopsy specimens were obtained after double labeling regime with oxytetracycline (Geomycin, Pliva). Biopsy specimens were processed for undecalcified embedding in resin and sections stained by Goldner trichrome and toluidine blue, or used for fluorescence microscopy. A grid attached to the microscope eyepiece was used for histomorphometry. The following parameters were assessed according to the recommendations of the American Society for Bone and Mineral Research: bone volume (BV/TV, %), osteoid surface (OS/BS, %), osteoblast surface (Ob. S/BS, %), osteoid volume (OV/BV, %), osteoid thickness (O. Th, m), osteoclast surface (Oc. S/BS, %), mineral apposition rate (MAR, m/day). Thus obtained data were compared to published reference data for normal healthy population and also expressed as z-scores (the number of standard deviations by which the value differs from the mean of the normal age and sex matched controls). The study was approved by the hospital ethics committee. All patients signed an informed consent to take part in the clinical study. DISCUSSION Histomorphometric analysis of bone biopsy demonstrated that on an average bone resorption, i.e. osteoclast surface, was considerably increased and osteoid volume moderately increased. The remaining histomorphometric parameters studied were generally normal for age and sex as compared to the published reference data. Increased osteoclast surface in 65% of patients indicated that bone loss was an active and prevailing process in these postmenopausal women, which was considerably more pronounced than in the normal age-matched population. Results of the histomorphometric analysis were categorized according to the published classification of postmenopausal osteoporosis. The percentage of patients in each group differed from literature data, most probably due to the sample size and choice. None of the patients had histomorphometric features of reduced osteoblastic and osteoclastic activity, but in 37% of postmenopausal women osteoclastic activity was increased while osteoblastic activity was normal, a feature not described in the original histomorphometric classification of postmenopausal osteoporosis. CONCLUSIONS Histomorphometric analysis of bone biopsy in women with postmenopausal osteoporosis revealed bone resorption as a predominant finding. Different groups were recognized based on the diversity of bone cell activity. The difference in the frequencies in study groups, and observation of a distinct group not included in the histomorphometric classification of postmenopausal osteoporosis probably resulted from sample size and nonspecific population traits. Histomorphometric analysis of bone in postmenopausal osteoporosis is an important contribution to better understanding of this most common bone disorder.

[Pseudomonas aeruginosa--a significant hospital pathogen and resistance to carbapenem].

Abstract: Pseudomonas aeruginosa (P. aeruginosa) is an etiologic agent of nosocomial infections of various localizations. The frequency of infections is a consequence of an increased number of immunocompromised patients, large surgical interventions, long-term hospital care and virulence factors of the bacterium. The use of carbapenems in the treatment of infections caused by P. aeruginosa and other gram-negative bacteria entail an unfortunate consequence of creating resistance to carbapenems. P. aeruginosa exhibits numerous mechanisms of resistance and is singularly problematic for combining intrinsic resistance and acquired resistance due to multiple mutations. It is also a carrier of the multiple-resistance plasmide. Carbapenems are a class of beta-lactam antibiotics with broad-spectrum activity to gram-positive, gram-negative and strictly anaerobic bacteria. The resistance of P. aeruginosa to carbapenems is complex and heterogeneous. It is determined by weakening the penetration through the outer membrane due to the loss of porin D2, decrease in the accumulation of antibiotic in the cell consequentially to active efflux due to hyperproduction of proteins, hydrolysis of carbapenem by specific metallo-beta-carbapenemases, and alteration in the target area of antibiotic activity on the bacterial cell. The loss of porin D2 results in resistance to imipenem with MIC values of 8.0-32.0 microg/mL. Selective low-level resistance to meropenem in the hyperproduction of the efflux system results in MIC values of 2.0-4.0 microg/mL. A high-level resistance to carbapenems with MIC values above 128 microg/mL for imipenem and meropenem is a consequence of the secretion of IMP and VIM series beta-carbapenemases. The frequency of resistance to P. aeruginosa to carbapenems varies worldwide from 15% to > or = 35%. In Croatia, resistance to carbapenems in the year 2003 was estimated to 12%. The problems in clinical practice are the increased resistance of P. aeruginosa to carbapenems, the presence of beta-carbapenemases and acquisition of these enzymes in certain types of Enterobacteriacea. The problems in laboratory practice are those of precise determination of the level and phenotype resistance of P. aeruginosa to carbapenems.

Importance of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration

Abstract: Paraneoplastic neurologic syndromes are disorders of the nervous system function caused by cancer but not due to metastatic disease, vascular or metabolic deficits, infections, nutritive deficiency, nor side effects of antineoplastic drugs or irradiation. Immunologic factors probably play the crucial role in the pathogenesis of paraneoplastic neurologic syndromes, but nonimmunologic mechanisms that include metabolic abnormalities and competition for substrate are also involved. Paraneoplastic cerebellar degeneration most commonly occurs in the setting of gynecologic cancers, but it accompanies the small-cell lung cancer too. Other tumors are infrequently associated with cerebellar degeneration. Several paraneoplastic antibodies have been identified in patients with paraneoplastic cerebellar degeneration. Their association with particular cancers may help identify an occult lesion. Anti-Yo antibodies are directed against Purkinje cell antigens and occur in patients with cerebellar degeneration who have breast cancer or gynecologic tumors. A target antigen of anti-Yo antibody is CDR2 protein that is normally expressed only in the brain and testis. Patients with paraneoplastic cerebellar degeneration present with dizziness, nausea and vomiting followed by gait instability, diplopia, gait and appendicular ataxia, dysarthria and dysphagia. Therapeutic options include tumor excision, chemotherapy and/or irradiation, and adjuvant therapy with glucocorticoids, immunoglobulins and plasmapheresis. The role of plasmapheresis in the treatment of paraneoplastic cerebellar degeneration is still uncertain. Reports of its efficacy are anecdotal. We present patient with paraneoplastic cerebellar degeneration with positive anti-Yo antibodies and tumor of the ovaries whose neurologic status significantly improved after four daily plasmaphereses, which was accompanied by a fourfold decrease in the anti-Yo antibodies titer. Further investigations are needed to define a protocol for plasmapheresis in the treatment of patients with paraneoplastic syndromes.

New biochemical markers in the assessment of minor myocardial damage in critically ill patients

Abstract: UNLABELLED The diagnosis of acute myocardial infarction (AMI) and unstable angina is based on typical clinical signs, electrocardiogram (ECG) changes, and serial measurements of characteristic serum enzymes, especially troponins. Today, newer biochemical markers are used in assessing these conditions, as well as minor myocardial damage (MMD). AIM The aim of this study was to determine the existence of MMD by the analysis of new biochemical markers including cardiac troponin T (c-TnT), troponin I (c-TnI), CK-MB activity (CK-MBact), CK-MB mass (CK-MBmass), a conventional marker of total creatine kinase (CK), and 12-lead ECG monitoring in two groups of critically ill patients admitted to the intensive care unit (ICU). Group 1 (n=52) consisted of the patients with heart failure, unexplainable hypotension, chronic obstructive pulmonary disease in acute exacerbation, acute severe pancreatitis, sepsis, pulmonary embolism, diabetes with complications, liver cirrhosis, and tachycardia >120/min who suffered chest discomfort without evident ECG signs of AMI. Group 2 consisted of patients (n=73) with acute gastrointestinal bleeding, poisoning, and miscellaneous conditions without chest discomfort or ECG signs of AMI. RESULTS Of the 52 critically ill patients, 21.2% were positive for troponin T and 11.5% for troponin I. Group 1 patients showed a prevalence of elevated total CK (28.8%), CK-MBact (7.7%), and CK-MBmass (32.7%). In group 2, positive troponin I was found in 19.7% of patients, troponin T was negative (0.00%), with elevated total CK (23.9%), CKMBact (7.0%), and CK-MBmass (2.3%). The mean concentrations of c-TnT, c-TnI, total CK, CK-MBact, CK-MBmass were higher in group 1 than in group 2, however, without statistical significance. The best positive correlation was recorded between CK-MBact and CK-MBmass (r=0.63). The c-TnI showed best discrimination and accuracy in the assessment of MMD under the ROC curves surface (0.84), while the accuracy was low for all other markers analyzed. Discrimination and accuracy were moderate for all markers analyzed. DISCUSSION AND CONCLUSION CK-MBact (92.3%) showed the highest specificity, followed by c-TnI (88.5%) and c-TnT (75.6%). The sensitivity was low for all markers analyzed. Concerning specificity, CK-MBact proved to be the best biologic marker for the assessment of MMD, followed by c-TnI and c-TnT. Correct clinical assessment according to marker accuracy and discrimination can be achieved by use of c-TnI, however, with a moderate degree of accuracy and discrimination for the detection of MMD in critically ill patients admitted to ICU.

Evaluation of justification for antibiotic use at the Internal Medicine Clinic of the Clinical Hospital in Zagreb

Abstract: Objective Resistance to antimicrobials as the result of unnecessary and inadequate use of antibiotics has become a global health problem It is estimated that up to 50% of antimicrobials are used unnecessarily, and that they are the cause of approximately 25% of adverse drug reactions Efforts are made to ensure a controlled use of antibiotics, which is the key strategy against development of resistance to antimicrobials Since antimicrobial drugs are among the most commonly prescribed drugs in hospitals, a rational use of antibiotics would also help reduce health care costs There are limited data on the use of antibiotics in Croatian hospitals Methods This observational study was conducted at the University Department of Medicine, Zagreb University Hospital Center, with the aim to investigate the prevalence of antimicrobial use, indications for antibiotic use, and the necessity and adequacy of antibiotic therapy The investigated parameters were: prescribed antibiotic (dose, route of administration, duration of therapy), indication for use of antibiotics (prophylaxis, treatment), diagnosis, presence of positive culture, indication documented in medical records, evaluation of antibiotic therapy by a specialist, and risk factors The most important parameter in the evaluation of the necessity of antimicrobial use was the presence of culture days of treatment, and indication for treatment documented in medical records and evaluated by a specialist The data were collected over 1 day using a standardized questionnaire Results Fifty of 138 (37%) hospitalized patients were receiving 1 or more antibiotics, most of them (80%) for the treatment of infection The most frequent diagnoses were sepsis (64%), urinary tract infection (25%), abdominal infection (21%), and pulmonary infection (7%) The median therapy duration was 4 days (minimum 1 day, maximum 121 days) The most frequently prescribed antibiotics were fluoroquinolones (23%), penicillins (23%), aminoglycosides (18%) and cephalosporins (11%) Thirty-nine patients received one or more reserve antibiotics The median number of received antibiotics was 2 (minimum 1, maximum 5 antibiotics) Risk factors were present in 76% of patients Fifty-nine percent patients were receiving antibiotics on the basis of culture; in most of them therapy was evaluated by a specialist (98%) and the indication was documented in medical records Reserve antibiotics were prescribed in 34 patients, in 77% of them on the basis of positive culture Conclusion The high prescription rate of antibiotics (fluoroquinolones), concomitant use of antibiotics of a similar spectrum of activity and lack of sequential therapy emerged to be the parameters needing further evaluation Other investigated parameters (number of antibiotics, duration of therapy, necessity of antibiotic therapy) were in accordance with similar studies conducted in hospitals Further investigation with emphasis on local problems and prescription habits with the aim to optimize the use of antibiotics is needed

[Comparison of biocompatibility of hemophane, cellulose diacetate and acrilonitile membranes in hemodialysis].

Abstract: INTRODUCTION The membranes used in haemodialysis (HD) may be manufactured from cellulose, modified cellulose or synthetic polymers. Such membranes, when in contact with blood, activate the complement system, which entails changes in leukocyte (L) and platelet (P) counts. The magnitude of complement activation depends on the type of membrane used, and represents the biocompatibility index. Acrylonitrile (AN69) is synthetic membrane of high biocompatibility standards, whereas haemophane (HP) and cellulosediacetate (CD) membranes are modified cellulose-based membranes. The biocompatibly profiles of HP, CD and AN69, characterised by changes in L and P counts and activation of complement components (C3a and C5b-9), has been studied in order to assess the biocompatibility features of HP, CD and AN69 membranes. MATERIALS AND METHODS We compared the generation of C3a des Arg and C5b-9 and the changes in L and P counts in groups of patients on HD who used HP (3 patients), CD (3 patients) and AN69 membrane (3 patients). Concentrations of C3a des Arg and C5b-9, and L and P counts were measured in the first HD session of the week, just before the start of HD (0 min) and after 15, 120 and 240 min. RESULTS For HP, L count at 15 min had declined to 50% of the pretreatment level (p < 0.05), compared with 59.3% (p < 0.05) for CD and with 98.7% (p = ns) for AN69, returning to the pretreatment level at 240 min. Statistically significant difference was found comparing L counts for HP vs AN69 (p < 0.001) and CD vs AN69 (p < 0.001). The mean plasma concentrations of C3a des Arg were 1246 +/- 832 ng/ml for HP, 1148 +/- 774 ng/ml for CD and 639 +/- 217 ng/ml for AN69 and significant difference was found comparing HP vs AN69, CD vs AN69 (p < 0.05). The maximal values of C3a des Arg occurred at 15 min in HP and CD (p < 0.005), whilst for AN69 the concentrations showed no statistically significant differences. The plasma concentrations of C5b-9 in patients on HP and CD were the highest at 15 min (p < 0.005), while those on AN69 did not show any statistically significant rise. DISCUSSION The fall in L counts was considerably marked for HP and CD membranes, with the lowest level at 15 min following blood exposure, thereafter returning to pretreatment level, whilst in AN69 leukopenia was not noted. The loss of L from the circulation is attributed to their pulmonary sequestration since complement activation and release of C5a fraction into the circulation results in their binding to the neutrophils and upregulation of the adhesion-promoting integrins of leukocytes, resulting in their binding to endothelial cells. The mean plasma concentrations of C3ades Arg, measured in the course of clinical use of HP and CD were significantly higher compared with synthetic membrane AN69, reaching the maximal level at 15 min. The complement activating potential of a biomaterial is one of its important biocompatibility features. The C3a complement activation curve is characteristic of cellulose-based materials and is governed by interaction between blood and hydroxyl groups on the membrane surface and by the density of hydroxyl groups available for the binding of C3b. The highest concentrations of C5b-9 in modified cellulose membranes were achieved by 15 min following blood exposure and met the activation curve for C3a. The capacity of AN69 membrane to adsorb anaphylatoxins may be a contributory factor for the failure to measure any increase in complement fraction concentration during HD for AN69. CONCLUSION There are significant differences between HP, CD and AN69 membranes concerning complement activation magnitude and leukopenia rate. Modified cellulose membranes HP and CD induce higher C3a concentrations and superior leukopenia rate compared with AN69. Synthetic membrane AN69 proved of higher biocompatibility, with lower efficiency of complement activation.

[Gaucher disease: diagnosis and treatment].

Abstract: Gaucher's disease is the most common lysosomal storage disorder. It was identified in 1882 by Phillipe Gaucher, a French dermatologist. However, it was not until 1965 that Gaucher disease was found to be due to a deficiency in the enzyme glucocerebrosidase (EC 3.2.1.45) which breaks down glucocerebroside, a cell membrane component. The deficiency in this enzyme leads to an accumulation of glucocerebroside within the lysosomes of macrophages throughout the body. Gaucher's disease is classified into three types: type 1 (non-neuronopathic), type 2 (acute neuronopathic), and type 3 (subacute neuronopathic). Of the three, type 1 is the most common, affecting one in 40,000-200,000 people and having a high prevalence among Ashkenazi Jews, affecting one in 450-1500. The signs and symptoms of type 1 disease demonstrate marked heterogeneity, from asymptomatic or mildly symptomatic, to severe disability with disfigurement and even death. Hepatosplenomegaly and thrombocytopenia are well documented. Less well-recognized are often insidious skeletal complications which affect the majority of type 1 patients and which are its most debilitating feature. In addition to clinical suspicion, some morphologic, hematologic and biochemical indicators can help establish the diagnosis. However, definitive diagnosis is only made by determining the catalytic activity of the lysosomal enzyme glucocerebrosidase. Confirmation of heterozygosity requires the use of molecular biotechnology methods. About 150 mutations of the glucocerebrosidase gene have been identified in patients with Gaucher's disease, some of which are predictive of phenotype. The history of treatment of Gaucher disease started with splenectomy and continued with bone marrow transplantation, before the recent introduction of safe and effective enzyme replacement therapy. In Croatia, nine patients with type 1 Gaucher's disease have been identified so far. Seven patients are on enzyme replacement therapy, and past results demonstrated significant improvement in all clinical symptoms, without development of any side effects. However, new treatments, such as substrate balance therapy and gene therapy, may become available within the next few years. The place, if any, that such therapies will have in the treatment of patients with Gaucher's disease will be dependent on the results of clinical studies currently in progress.

Etiology of atypical pneumonias in 2002. Results of the Croatian Institute of Public Health

Abstract: AIM This investigation was performed at Department of Virology, Croatian National Institute of Public Health, the same diagnostic laboratory using the same serologic method as in earlier studies (in 1982 and 1992) to determine the incidence of the most common agents of atypical pneumonia in Croatia between January 1 and December 31, 2002. PATIENTS AND METHODS The study included 630 patients from nearly all regions of Croatia with a clinical diagnosis of atypical pneumonia based on epidemiologic data, clinical symptoms, laboratory findings and chest X-rays. Most of them were from Zagreb (n = 370), followed by those from Slavonia, Istria, northwest Croatia, and Dalmatia. In all of them paired sera were collected at an interval of two weeks or more and tested for complement-fixing (CF) antibodies against the most common causative agents of the atypical pneumonia syndrome using CF test (micromethod). RESULTS An etiologic diagnosis was established in 25% (158/630) patients (81 male and 77 female). Respiratory viruses were the most frequently demonstrated pathogens in 2002, accounting for 72% of cases (adenoviruses 47%, parainfluenza viruses 14%, influenza viruses 9% and respiratory syncytial virus (RSV) 2%). These were followed by Chlamydophila (C.) psittaci; (19%), Mycoplasma (M.) pneumoniae; (6%) and Coxiella (C.) burnetii (3%). There were 3 cases of double infection: a combination of adenovirus and M. pneumoniae, of RSV and parainfluenza virus, and of RSV and M. pneumoniae in one patient each. Adenoviral, mycoplasmal and psittacosal pneumonia occurred throughout the year; influenza and most of RSV pneumonias occurred in winter months. Parainfluenza viruses caused pneumonias throughout the year but were more common in winter months. CF test does not distinguish type-specific antibodies to parainfluenza viruses. In March, a small epidemic of psittacosis (11 patients) was registered in the Split area while was responsible for the high incidence of psittacosal pneumonia in 2002. While M. pneumoniae-caused pneumonia occurred mainly in children and adolescents, viral pneumonias were distributed across all age groups. Psittacosal pneumonia occurred in only one child but was more common in adolescents and especially adults. Q-fever pneumonia occurred only in adults.

Knowledge and attitudes on breastfeeding among parturients

Abstract: UNLABELLED During human history, the natural process of breastfeeding has become ever less present as a mode of infant feeding. Numerous incentives have been introduced worldwide to stop this unfavorable trend. AIM OF THE STUDY The aim of the study was to find the basic attitudes and knowledge about breastfeeding among mothers after delivery while they were at maternity wards. METHODS Two surveys were conducted, with 940 participants in 1989-1990, and 626 participants in 1997. The women answered a self administered questionnaire with multiple choice questions. Data from the 1989-1990 and 1997 surveys were analyzed and compared. RESULTS AND DISCUSSION A high percentage of women (98%), stated that they wanted to breastfeed their children, but only about 44% of them expected it to be problem-free. A great number of women did not know how and when to estimate milk secretion, or its adequacy for the baby. A significant proportion of the mothers believe that milk of some women is "watery" and thus inappropriate for their children. A great number of mothers (83%), answered correctly that the child need to be fed on demand rather than according to a strict schedule. In the second phase of the survey some positive changes in their knowledge were found, however, yet quite inadequate. CONCLUSION Comprehensive and continuing education about breastfeeding of future mothers and fathers and the society as a whole is required.

[Antibiotic resistance--bacteria fight back].

Abstract: Antibiotic resistance has become one of the leading problems in modern medicine. Resistance to antibiotics emerges in bacteria due to genetic mutations and consecutive selection of resistant mutants through selective pressure of antibiotics present in large amounts in soil, plants, animals and humans. Exchange of genetic material coding for resistance is possible even between unrelated organisms and further promotes the spread of resistance. Constantly evolving resistance mechanisms force experts to redefine breakpoint concentrations and interpretation of in vitro antibiotic sensitivity testing. Developing new antimicrobial agents does not seem to be enough to keep up pace with ever changing bacteria. Using antibiotics prudently and developing new approaches to the treatment of infections is vital for the future. The European Antimicrobial Resistance Surveillance System (EARSS) data clearly show that Scandinavian countries and The Netherlands have the lowest rates of resistance, while Southern and Eastern European countries have the highest prevalence of resistance. This is linked to the European Surveillance of Antimicrobial Consumption (ESAC) data that show very low consumption of antibiotics in Scandinavian countries and The Netherlands. Compliance with strict infection control policies related to multidrug resistant organisms is also high in these countries. Although it is important to be aware of the resistance problems worldwide, rational use of antibiotics should be based on the knowledge of local resistance patterns in common pathogens. Since 1996 there is a continuous surveillance of resistance in Croatia through the Croatian Committee for Antibiotic Resistance Surveillance. There is a particular concern about the rising penicillin and macrolide resistance in pneumococci. In Croatia, data for 2002 suggest that resistance to penicillin in pneumococci was 30% (low level) and 2% (high level). Among invasive isolates, 19% had reduced susceptibility to penicillin (< 1% high level resistance) as compared with 1% in The Netherlands and 53% in France. While methicillin-resistant Staphylococcus aureus (MRSA) has become endemic in many hospitals throughout the world, the most alarming event in 2002 was detection of Staphylococcus aureus fully resistant to vancomycin (VRSA). Of great concern is also reporting of MRSA community outbreaks in some parts of the world. Multiply resistant gram-negative pathogens, especially non-fermentative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumanii, have become dominant in many intensive care settings and some of these strains cannot be treated with any of the currently available systemic antibiotics. Raising awareness about the microbial resistance threat among health care workers and patients is essential if we are to preserve the efficacy of antibiotics for future generations.

Work capacity in patients on hemodialysis

Abstract: The quality of life is considerably impaired in patients on regular hemodialysis has been changed. It is difficult to determine it because there are no general definitions or measuring instruments. There are objective and subjective components of the quality of life, one among them being occupational ability. During the progression of chronic renal disease (CRD) to terminal renal failure (TRF) physical activity of the patients becomes poorer. In this stage, their physical activity is by 40-60% below the value expected for the same healthy age cohort. The intention of this analysis was to determine occupational ability in patients on regular hemodialysis. The analysis included 161 patients on hemodialysis, 78 (48.5%) female and 83 (51.5%) male, mean age 61.2 +/- 13.1 years, and mean time on hemodialysis was 54 +/- 71.9 months. All patients filled-out a self-administered questionnaire on schooling and occupational ability. The cause of TRF was glomerulonephritis in 45 (26.8%), diabetes mellitus in 42 (26.3%), nephrosclerosis in 26 (16.1%), and pyelonephritis in 12 (7.4%) patients. Age distribution was as follows: 0-19 years 1 patient, 20-44 years 14 (8.7%); 45-64 years 64 (39.8%) and 65 years 82 (50.9%) patients. Educational structure: elementary school 65 (40.4%), secondary school 79 (49.1%), college 10 (6.2%), and university 6 (3.7%) patients. Occupational structure: retired 123 (76.4%), housekeeper 20 (12.4%), never employed 4 (2.5%), employed 10 (6.2%), unemployed 2 (1.2%), 1 child and 1 student. Among employed patients there were 7 men and 3 women. Their educational level was as follow: elementary school 1 patient, secondary school 8 patients, college 1 patient. At the beginning of hemodialysis their occupational status was: full-time employment 30 (18.6%) patients, part-time employment 1 patient, longer time on sick-leave payment (3.1%), retired 95 (59%), pupils and students 3, unemployed 2, and 1 child did not attended school. Time interval between the beginning of hemodialysis and retirement was: less than 1 year work 13 (36.1%) patients, 1-2 year work 6 (16.7%), three year work 2 patients, more than 8 year work 2 patients, and 10 year work only 3 patients, for 14, 18 and 26 years each. Two patients lost their job for employer bankruptcy. The judgment of patients regarding their occupational ability was as follows: out of 161 patients, 23 (14.3%) felt fit for work, 12 on full-time and 11 on part-time basis. Occupationally incapable were 46.6% of patients, and 63 felt unable to take care of another person. Some kind of additional activity, like working in garden or taking care of children was reported by 26 patients. The aforementioned results showed that 22.4% of the patients were occupationally active at the time of starting hemodialysis. Many patients were retired after hemodialysis had started. Only 6.2% of hemodialysis patients were occupationally active although 14.3% felt occupationally capable. The main reasons for such a low level of employment were advanced age, diminished physical activity due to the disease, and difficulties associated with the socioeconomic situation in the country.

Clinical characteristics of pruritus in hemodialysis patients

Abstract: AIM Aim of the research was to analyze clinical characteristics and most important risk factors of uremic pruritus. PATIENTS AND METHODS A total of 151 patients on chronic hemodialysis (CHD) during at least 12 months were analyzed. Thorough history was taken for pruritus, its presence and localization, sleep disorder and neuropathic symptoms. On physical examination, attention was focused on the skin. Laboratory tests includes blood cells count, serum urea, creatinine, electrolytes, aminotransferases, alkaline phosphatase and proteins. The dose of dialysis was followed by Kt/V. On statistical analysis, t-test and chi2 test were used. RESULTS Pruritus was present in 85 (56%) patients, 41 women and 44 men, mean age 53.56+/-13.36 (26-81) years, mean time on CHD 78.36+/-55.02 (12-268) months. There were 66 (44%) patients without pruritus, 32 women and 34 men, mean age 50.35+/-13.76 (22-73) years, on CHD for 58.64+/-50.40 (12-187) months. Although the patients with pruritus were somewhat older and longer on CHD, there was no significant difference either in sex structure or distribution according to primary renal disease. In the group with pruritus there were significantly more anuric patients (43 vs. 22) (p<0.01). The patients with pruritus had a higher rate of sleep disorder (NS), calcium deposits in soft tissues and blood vessels (NS) and clinical neuropathy (p<0.01). Skin changes were found in almost all patients with pruritus (93%), which differed significantly from the patients without pruritus (48%) (p<0.005). The mean value of Kt/V was 1.23+/-0.35 in patients with pruritus, and 1.34+/-0.41 in those without pruritus (NS). Kt/V higher than 1.4 was significantly less frequently recorded in patients with pruritus than in those without pruritus (55%) (p<0.005). The red cell and white cells count, serum hemoglobin, calcium, phosphorus and their products, aminotransferases, bilirubin, alkaline phosphatase and proteins were approximately the same in both groups of patients. CONCLUSION The loss of residual renal diuresis, Kt/V below 1.4, presence of calcium deposits and neuropathy were the most common risk factors for the extent of uremic pruritus in our CHD patients.

ACE inhibitors and angiotensin II receptor antagonists in acute coronary syndrome

Abstract: Angiotensin II (AT II) is a final product of the renin-anglotensin-aldosterone system (RAS) and presents one of the most influential factors in the pathogenesis of atherosclerosis, acute coronary syndrome, myocardial dysfunction and heart failure. ACE-inhibitors (ACEI), beside beta adrenergic blockers, are a cornerstone of the current chronic heart failure (CHF) treatment. Evidence based medicine has not yet proved any significant beneficial effects of ACEI in patients with unstable angina pectoris (UAP), although according to the SoLVD study testing the possible effects of ACEI in patients with significant left ventricular dysfunction and/or CHF, there was a significant hospitalization rate reduction as well as less transformation of UAP to myocardial infarction in patients treated with ACEI. In the GISSI 3, ISIS 4 and CCS studies, ACEI was given within the first 24 hours and continued for 4-6 weeks. According to pooled results, ACE inhibitor could save 11/1000 patients with ST-elevation myocardial infarction (STEMI) and only 1/1000 patients with non ST-elevation myocardial infarction (NSTEMI). In the SAVE, AIRE and TRACE studies, ACEI was started later, i.e. 3-16 days after acute myocardial infarction and continued for several years. ACEI therapy resulted in a significantly lower mortality during the first year, and an even 20% relative reduction in the total mortality during the 4-year follow up. The effects of ACEI were even more prominent in more severe myocardial dysfunction, as it was well known that they could slow or stop unfavorable myocardial remodeling. Conclusively, ACEI should be given as early as possible to all patients with acute myocardial infarction, if no contraindications. The HOPE study showed efficacy of ACEI in the primary prevention of ischemic heart disease in high risk individuals, and the EUROPA study showed a favorable effect of ACEI in the secondary prevention of ischemic heart disease in low risk patients. According to these findings, ACEI should be given permenantly following myocardial infarction. These findings suggest the need of a permanent treatment with ACEI in patients having sustaned myocardial infarction. Angiotensin-1 receptor antagonists (AT-1 antagonists) are a newer generation of neurohormonal antagonists, which block the effects of AT II produced not only through a classic, ACE-dependent pathway but also via alternative pathways (non ACE-dependent) and selectively bind to AT-1 receptors for AT II. Therefore, they have some theoretical advances in comparison with ACEI. There are 2 relevant studies elucidating their possible role in treating patients with or post-myocardial infarction. The OPTIMAAL study did not prove losartan to be better than an ACEI (captopril), while the VALIANT study showed that the effects of valsartan vs. captopril were statistically nonsignificantly different. Furthermore, there is no sense to combine AT-1 antagonist and ACEI, while a combination of AT-1 antagonist and a beta blocker is justified. In other words, AT-1 antagonist (the class effect is disputable) should be given to patients with acute myocardial infarction or to post-myocardial infarction patients who cannot take ACEI.

[Drug-resistant tuberculosis: resistance mechanisms and drug susceptibility of Mycobacterium tuberculosis].

Abstract: Mycobacterium (M.) tuberculosis is the most common individual causative agent of infectious disease in the world. It is responsible for 26% of preventable deaths in adulthood. Because the number of new cases grows at an annual rate of 2%, in 1993 WHO proclaimed tuberculosis a global health problem. The immediate cause for this was coinfection with causative agents of tuberculosis and human immunodeficiency virus, and spread of resistant and multiresistant strains of M. tuberculosis (MDR TB). It is estimated that 50 million people are infected with resistant strains of M. tuberculosis. Tuberculosis has emerged as a major public health problem for its high mortality (50%-80%) in the first 4-16 weeks of the disease and 100 times more expensive therapy for drug-resistant than for drug-susceptible tuberculosis. Mycobacteriologic laboratories play a fundamental role in the detection, combat and control of tuberculosis, especially in preventing the spread of drug-resistant tuberculosis. In this connection, there is an increased need of a rapid and reliable determination of the susceptibility of isolated strains of M. tuberculosis to the first- and second-line antituberculotic drugs.

Importance of biochemical indicators of bone turnover in patients on chronic dialysis and after kidney transplantation

Abstract: Bone remodeling is a continuous process of removal of microscopic amounts of bone tissue due to synchronized actions of osteoclasts and osteoblasts with the purpose of renewal and repair of bone tissue. During the formation of bone matrix osteoblasts synthesize proteins. Measurement some of these proteins in blood has clinical significance as indicators of bone formation: osteocalcin, procollagen type I propeptide, and bone alkaline phosphatase. During osteoclastic bone resorption, collagen type I breakdown fragments are released in the circulation and excreted in the urine, and measured in serum or urine as bone resorption markers (telopeptide, pyridynolines). Bone metabolism and accordingly bone markers are subjected to considerable biologic variation. The effects of age, sex, race, pregnancy and lactation, fracture, disease and certain drugs cannot be avoided and must thus be considered when interpreting the results. Circadian variation is excluded by obtaining samples in the morning and the effect of exercise prevented. The use of bone markers has been extensively studied in monitoring the effect of antiresorptive treatment in osteoporotic women. A decrease of 30-50% occurs within 3 months after the beginning of hormone replacement therapy or bisphosphonates and remains at this level. In patients on chronic dialysis treatment, bone markers are increased and reflect bone metabolism as assessed by bone biopsy. Although bone markers enable discrimination between high and low bone turnover, they cannot substitute for bone biopsy in determination of the type of renal osteodystrophy. The factors affecting bone disorder in these patients, i.e. dialysis duration or parathyroid function correlate with bone markers. In kidney transplant recipients, an increased bone turnover and its normalization after approximately 2 years can be assessed by bone markers. Similar to chronic dialysis, risk factors for bone disorder after kidney transplantation (e.g., dialysis duration, parathyroid function, age, sex, immunosuppressants, corticosteroids, graft function) are associated with bone markers. We present cross-sectional and longitudinal data on 100 patients on chronic dialysis and 80 kidney transplant recipients. In conclusion, sufficient evidence exists indicating that the measurement of bone markers enables assessment of bone turnover and its dynamics. However, no guidelines or recommendations have been put forward to validate their use in routine clinical practice of chronic dialysis or kidney transplantation bone disorders.

[Stents without restenosis--true or a myth?].

Abstract: Routine stent implantations have significantly improved the results of percutaneous coronary angioplasty. In relation to balloon dilatation, the intervention success is improved, while restenosis as well as recurrence of progressive atherosclerotic disease at the site of previous dilatation are significantly reduced. In complicated interventional procedures such as dilatation of multi-vessels, long lesions, left main lesion, bifurcation lesions, dilatation of small vessels, and lesions in patients with diabetes mellitus in spite of stent implantation, the incidence of restenosis remains high, about 30%-50%. The introduction of drug-eluting stents (DES) such as sirolimus, paclitaxel and dexamethasone in interventional cardiology has brought important improvement with a significantly decreasing incidence of in-stent restenosis. Despite great enthusiasm and very good initial results, it should not be forgotten that the usage of these stents is still experimental, with many questions, especially concerning longterm results and use of DES in complicated interventional procedures.

Choice of antimicrobial drug for infections caused by Chlamydia trachomatis and Chlamydophila pneumoniae

Abstract: Chlamydia (C.) trachomatis is the most common bacterial cause of sexually transmitted disease in the world. A well documented feature of chlamydial infection is its high rate of recurrence among sexually active populations. However, it is difficult to distinguish whether the high rate of recurrent disease is due to reinfection or to persistent infection with the same organism. Of particular concern in this era of increasing antibiotic resistance is whether persistent infection is the consequence of increasing resistance to standard antimicrobial therapy. Azithromycin and doxycycline are considered by the Centers for Disease Control and Prevention (CDC) as first line drugs for the treatment of chlamydial infections; erythromycin, ofloxacin and levofloxacin are recommended as alternative-regimen. Although C. trachomatis has been historically sensitive to these antibiotics, in vitro resistance is being increasingly reported. However, although in vitro antimicrobial resistance has been described, the clinical significance of these findings is unknown. C. pneumoniae is associated with community-acquired pneumonias, acute exacerbations of chronic bronchitis, otitis media, sinusitis and reactive airway disease. Persistent nasopharyngeal infection with C. pneumoniae has been documented in adults following acute respiratory infection. Chronic infection with C. pneumoniae has also been implicated in the pathogenesis of atherosclerosis, although this is still very controversial. Azithromycin, clarithromycin and quinolones are frequently used for the treatment of C. pneumoniae respiratory infections. Microbiologic failure has been described in C. pneumoniae infections, even after prolonged courses of azithromycin, erythromycin and doxycycline.

Coagulation tests in septic surgical patients

Abstract: AIM To determine whether sequential change in coagulation parameters such as activated partial thromboplastin time (aPTT), prothrombin time (PT), platelets count and fibrinogen level may predict the outcome of patients in sepsis. STUDY DESIGN Cohort longitudinal study. PATIENTS AND METHODS Patients with positive two or more clinical criteria for sepsis were eligible for the study. Thirty patients were included, 24 male and 6 female. Eight patients survived, while 22 deceased. Median age of survivors was 66 years (range 23-77), and in non-survivors it was 69 years (range 48-79), p=0.37. In 9 patients malignancy was an underlying disease. APACHE II score was calculated at admittance, median value for survivors was 10 (range 7-15) and for non-survivors it was 26 (range 6-35), p=0.001. Calculated MODS score at the time blood cultures was 2 (range 0-9) for survivor and 6.5 (range 2-13) for non-survivors, p=0.007. Blood cultures were taken at the onset of sepsis, and in 29 patients they were positive. Coagulation parameters were measured at admittance, at the onset of sepsis and 48 hours after the introduction of the specific antimicrobial therapy. RESULTS Analysis of variance for repeated measurements between survivors and non-survivors has shown that there were no differences in values of coagulation parameters. The only significant difference between these groups of patients was APACHE II and MODS score. In 7 patients with severe thrombocytopenia (<33,000 x 10(9)/L) as a result of irreversible septic shock a clinically visible bleeding was present in only one patient. DISCUSSION Disseminated intravascular coagulation (DIC) is a clinical-pathological syndrome in which wide-spread intravascular coagulation is induced by procoagulants that are introduced or produced in the blood circulation and overcome the natural anticoagulant mechanisms. DIC causes tissue ischemia from occlusive microthrombi as well as bleeding from both the consumption of platelets and coagulation factors and the anticoagulant effect of products of secondary fibrinolysis. In sepsis, tissue factor which is the most common trigger of DIC can be generated and expressed on membranes of monocytes and endothelial cells during the systemic inflammatory response syndrome (SIRS). The wide-spread generation of thrombi in sepsis induces deposition of fibrin which leads to vessels obstruction and consumption of substantial amounts of haemostatic factors i.e. platelets, fibrinogen, factors V, VIII and others, protein C and antithrombin III (AT III). Intravascular thrombi trigger secretion of tissue plasmin activator (tPA) from endothelial cells which sets of compensatory thrombolysis which may reopen the occluded blood vessels. But byproducts of thrombolysis such as fibrin/fibrinogen degradation products may enhance bleeding by interfering with platelet aggregation, fibrin polymerization and thrombin activity. The typical feature of sepsis is depression of three powerful anticoagulant systems: protein C pathway, AT III pathway and tissue pathway factor inhibitor (TPFI). This sequence of events led us to hypothesize that alterations in coagulation parameters such as PT, aPTT, fibrinogen, platelets count may predict the outcome of disease, as it is well documented that the development of DIC confers prognosis of sepsis. The failure to distinguish survivors from non-survivors by the alteration in the coagulation parameters in this study may be due to a relatively low sample size or to the clinical necessity of an attending physician to substitute the deficient blood or coagulation product. CONCLUSION The coagulation parameters PT, aPTT, platelet count and fibrinogen level can not serve as predictors of outcome in patients with sepsis. Further studies including more discerning coagulation parameters: AT III, D-dimer, soluble fibrin monomer, thrombin/antithrombin complex, plasmin/antiplasmin complex, fibrinopeptid A, fibrinopeptid B are necessary to evaluate whether these procoagulant and anticoagulant factors may help in predicting outcome and severity of sepsis.

Acute renal failure in patients undergoing cardiac surgery

Abstract: Akutno zatajenje bubrega (ABZ)je ozbiljna komplikacijakoja se može javiti u bolesnika podvrgnutih kardiokiruskom zahvatu. Incidencija varira od 1% do 15% uz visok mortalitet bolesnika kojima je bilo potrebno lijecenje jednom od dijalitickih metoda. Ispitali smo ucestalost ABZ-a nakon kardiokiruskih zahvata u 290 bolesnikakoji su operirani u razdoblju od 1.1.2001. do1.6.2002. Od ukupnog broja bolesnika, 71(24, 5%) bilo je žena i 219 (75, 5%) muskaraca u dobi od 17do 81 godine. Kriterij po kojem smo definiraliakutno zatajenje bubrežne funkcije bilo je udvostrucenje koncentracije serumskog kreatinina u bolesnika u kojih je prijeoperacijska vrijednost iznosila do 130 µ ; mol/L, odnosno poradt vrijednosti serumskog kreatinina za 100 µ ; mol/L poslije operacije. ABZ se javilo samo u 8 (2, 1%)bolesnika. U jedne je bolesnice bilo potrebno lijecenjehemodijalizom i kontinuiranom veno.venskom hemofiltracijom, a svi ostali bolesnici lijceni su konzervativno. Smrtni ishod nastupio je kod dvoje bolesnika ukljucujuci i bolesnicu lijecenu dijalizom. U svih se ostalih bolesnika bubrežna funkcija u potpunosti oporavila. U usporedbi s rezultatima nase ustanove od prij 17 godinaznacajno je manji broj bolesnikau kojih je ABZ bilo potrebno lijeciti dijalizom (0, 3% u usporedbi s prijasnjih 4%).

Pathophysiologic basis of the treatment of neurogenic pain

Abstract: According to the International Association for the Study of Pain (IASP) neuropathic pain is "pain initiated or caused by a primary lesion or dysfunction or transitory perturbation in the peripheral or central nervous system". Neuropathic pain is usually classified according to the etiology, location of the lesion, and pain characteristics--individual symptoms and signs, but also according to the possible mechanisms involved. Identifying the underlying pain mechanisms during the diagnosis becomes essential for treatment strategies. The clinical picture of neuropathic pain is similar in many cases, and clinical features include: ongoing spontaneous or evoked pain in an area with sensory loss, positive sensory symptoms such as allodynia and hyperalgesia, wind-up pain following repetitive stimulation, referred pain and abnormal sympathetic activity. The understanding of the mechanisms underlying neuropathic pain has increased over the last decade. The primary pathophysiologic mechanisms that produce pain are: nociceptor sensitization, nerve trunk inflammation, sympathetic nervous system involvement, ectopic neuronal discharges, pathologic synaptic reorganization--neuroplasticity and central sensitization. In most clinical features, there is a complex interaction that involves peripheral and central nervous system rather than a single mechanism. Because numerous mechanisms are implicated, the traditional approach to pain control using single drug therapy may not be most effective, and therapeutic combinations are a better choice. Neuropathic pain is poorly responsive to conventional analgesics. In spite of a variety of drug classes used to treat neuropathic pain including antidepressants, anticonvulsants, antiarrhythmics, opioids, local anesthetic blockers, neuropathic pain remains difficult to treat. The possibility to select specific drugs and treatments for the individual patient lies in elucidating the relationships between clinical neuropathic states and underlying pathophysiologic changes. Progress in defining the mechanisms involved in neuropathic pain, based on further clinical studies and fundamental investigations, will improve therapeutic management of neuropathic pain.

Value of urinary sediment cytology in evaluation of acute tubular necrosis after kidney transplantation

Abstract: Akutna tubularna nekroza (ATN) je najcesci uzrok odgođene funkcije bubrežnog transplantata u ranom razdoblju nakon ucinjene transplantacije. Cilj rada je analizirati vrijednost citologije sedimenta mokrace (CSM) primjenom mikroskopa s faznim kontrastom u evaluaciji ATN tijekom ranog poslijetransplantacijskog razdoblja. U 141 bolesnika citoloski je analiziran sediment mokrace (SM). Bilo je 99 (70, 2%) muskaraca i 42 (28, 8%) žene, prosjecne dobi 40±13 godina (raspon 8-72 godine), kojima je presađen bubreg u KBC-u Rijeka, u vremenu od 10 godina (od 1990. do 2000. godine). Vecina bolesnika (76%) je dobila bubreg od umrle osobe. SM je analiziran na prisustvo stanica bubrežnih kanalica, izomorfnih eritrocita, limfocita, cilindara i detritusa. Citoloski kriterij za ATN bio je prisustvo stanica bubrežnih kanalica, cilindara, stanicnog i/ili amorfnog detritusa, te isomorficnih eritrocita, granulocita i rijetkih limfocita u pozdadini. Stanice bubrežnih kanalica su najkonstantniji nalaz u SM tijekom ATN. Veci broj limfocita može zadavati diferencijalno-dijagnosticke teskoce u razlucivanju od odbacivanja. U evaluaciji ATN CSM primjenom mikroskopa s faznim kontrastom pokazala se metodom visoke osjetljivosti (82%) i specificnosti (93%). Primjenom te metode citoloski profili odbacivanja bili su cesce prepoznati u epizodama bez ATN (37% prema 9, 1%, p<0, 001). U slucajevima preklapanja vise patoloskih entiteta, primjerice ATN i odbacivanja, CSM je od male pomoci. U tim je slucajevima potrebna histoloska evaluacija transplantata, koja jedina može dati pravu sliku o zbivanjima in situ. Autori zakljucuju da je CSM primjenom mikroskopa s faznim kontrastom jednostavna, neinvazivna, brza, jeftina i pouzdana metoda visoke osjetljivosti i specificnosti u dijagnostici ATN u ranom poslijetransplantacijskom razdoblju.

Should we begin with statin therapy in acute coronary syndrome

Abstract: Acute coronary syndrome (ACS) constitutes a unique syndrome with a distinct pathophysiology: rupture of the fibrous cap of unstable atherosclerotic plaques in coronary arteries resulting in subsequent platelet deposition and a thrombus formation that completely or partially occludes the artery. Remarkable therapeutic advances in the treatment of ACS have been made during the past decade with antiplatelet and antithrombotic therapy. However, these therapies alone do not appear to completely stabilize the unstable plaque. Results from several clinical trials suggest that early administration of a statin following an ACS may reduce both short-term and longterm adverse outcomes such as subsequent cardiovascular mortality, myocardial infarction and revascularization. The potential mechanisms of benefit include improvements in endothelial function and vasomotion, reduction of platelet aggregability and thrombus formation, fibrinolytic and antioxidant activity as well as reduction of inflammation within plaques, reducing matrix degradation due to reduction of macrophage metalloproteinase production and increasing collagen content. Based upon the current knowledge, it might be concluded that patients hospitalized for ACS should be given a statin and the treatment should be initiated as soon as possible.

Inflammation markers in acute coronary syndrome

Abstract: Inflammation is a component of atherosclerotic plaque, but it is also a possible pathogenetic factor of acute coronary event responsible for coronary instability. Inflammatory markers are considered as new risk factors for atherosclerosis. Among others (C-reactive protein (CRP) is the best known marker of inflammatory response which is most frequently found in patients with acute myocardial infarction preceded by a period of instability. High values of inflammatory markers indicate poor prognosis after acute myocardial infarction. Therapy may lower the inflammatory component and the risk of coronary disease. Specific response of inflammatory marker during diagnostic and percutaneous coronary interventions indicates more severe coronary disease.

[Differentiation of resistance phenotypes among erythromycin-resistant streptococci].

Abstract: Although macrolide antibiotics have proved to be a valuable alternative to beta-lactam antibiotics in the treatment of respiratory tract infections, resistance to these agents is now becoming established in streptococci, especially among Streptococcus pneumoniae isolates. Of particular concern is the emergence of cross-resistance to 14-, 15- and 16-membered macrolides, licosamides and group B streptogramins (MLSb phenotype). MLS resistance can be expressed either constitutively (cMLS phenotype) or inducibly (iMLS phenotype). MLS resistance is mediated by two classes of methylase genes--the conventional erm(B) and recently described erm(A) determinants. A new macrolide efflux mechanism has been described for streptococci, in which it is associated with a new resistance pattern (M phenotype) characterized by resistance to 14- and 15-membered macrolides, and susceptibility to 16-membered macrolides, lincosamides and streptogramin B. The recognition of the prevalence of M phenotype in streptococci has implications for sensitivity testing and may have an impact on the choice of antibiotic therapy in clinical practice. While M resistance is similar in S. pyogenes and S. pneumoniae being mediated by mef(A) and mef(E), respectively, MLS resistance in both species appears to be genotypically and phenotypically more varied. Differentiation of M and MLS phenotypes of erythromycin-resistant strains can be performed using the erythromycin-clindamycin double-disc method (ECDD). Distinguishing not only M resistance but also constitutively or inducibly MLS phenotype by ECDD in S. pyogenes is easily and reliably achieved. Inducible MLS phenotype S. pyogenes strain is genotypically and phenotypically heterogeneous and is further subdivided into three recently described subtypes, iMLS-A, iMLS-B and iMLS-C, by a triple-disk test with erythromycin plus clindamycin and josamycin. While distinguishing M from MLS resistance in S. pneumoniae by ECDD test is easily and reliably achieved, the differentiation between constitutive and inducible MLS resistance is by far more uncertain. The meaning of inducible MLS resistance appears to be different in S. pneumoniae from that in S. pyogenes. In order to easily differentiate, within erythromycin-resistant pneumococci, not only the strains of the M phenotype from those with MLS resistance but also among the latter, cMLS from iMcLS strains, a triple-disk test has been set up by adding a rokitamycin disk to the conventional