Oral teicoplanin versus oral vancomycin for the treatment of severe Clostridium difficile infection: a prospective observational study.

The aim of this study was to compare clinical cure rate, recurrence rate and time to resolution of diarrhea in patients with severe and severe-complicated Clostridium difficile infection (CDI) treated with teicoplanin or vancomycin. This two-year prospective observational study included patients with first episode or first recurrence of CDI who had severe or severe-complicated CDI and were treated with teicoplanin or vancomycin. Primary outcomes of interest were clinical cure rate at discharge and recurrence rate after eight weeks follow up, and secondary outcomes were all-cause mortality and time to resolution of diarrhea. Among 287 study patients, 107 were treated with teicoplanin and 180 with vancomycin. The mean age of patients was 73.5 ± 10.6 years. One hundred eighty six patients (64.8%) had prior CDI episode. Severe complicated disease was detected in 23/107 (21.5%) and 42/180 (23.3%) patients treated with teicoplanin and vancomycin, respectively. There was no statistically significant difference in time to resolution of diarrhea between two treatment arms (6.0 ± 3.4 vs 6.2 ± 3.1 days, p = 0.672). Treatment with teicoplanin resulted in significantly higher clinical cure rate compared to vancomycin [90.7% vs 79.4%, p = 0.013, odds ratio (OR) (95% confidence interval (CI)) 2.51 (1.19-5.28)]. Recurrence rates were significantly lower in patients treated with teicoplanin [9/97 (9.3%) vs 49/143 (34.3%), p < 0.001, OR (95%CI) 0.20 (0.09-0.42)]. There was no statistically significant difference in overall mortality rate. Teicoplanin might be a good treatment option for patients with severe CDI. Patients treated with teicoplanin experienced remarkably lower recurrence rates compared to vancomycin-treated patients.

Fractal analysis and Gray level co-occurrence matrix method for evaluation of reperfusion injury in kidney medulla.

Fractal analysis and Gray level co-occurrence matrix method represent two novel mathematical algorithms commonly used in medical sciences as potential parts of computer-aided diagnostic systems. In this study, we tested the ability of these methods to discriminate the kidney medullar tissue suffering from reperfusion injury, from normal tissue. A total of 320 digital micrographs of Periodic acid-Schiff (PAS) - stained kidney medulla from 16 Wistar albino mice (20 per animal), were analyzed using National Institutes of Health ImageJ software (NIH, Bethesda, MD) and its plugins. 160 micrographs were obtained from the experimental group with induced reperfusion injury, and another 160 were obtained from the controls. For each micrograph we calculated the values of fractal dimension, lacunarity, as well as five GLCM features: angular second moment, entropy, inverse difference moment, GLCM contrast, and GLCM correlation. Discriminatory value of the parameters was tested using receiver operating characteristic (ROC) analysis, by measuring the area below ROC curve. The results indicate that certain features of GLCM algorithm have excellent discriminatory ability in evaluation of damaged kidney tissue. Fractal dimension and lacunarity as parameters of fractal analysis also had a relatively good discriminatory value in differentiation of injured from the normal tissue. Both methods have potentially promising application in future design of novel techniques applicable in cell physiology, histology and pathology.

Paroxetine mitigates cardiac remodelling by doxorubicin and increases survival.

Doxorubicin (DOX) is an effective anticancer drug. However, its use is hampered by the development of very mortal cardiomyopathy. Here, we investigate whether the co-administration of the antidepressant paroxetine (P), known to exert beneficial cardiovascular effects, would provide effective cardioprotection. Experiments were performed in male Wistar rats randomly assigned to control group (0.5 mL/kg 0.9% NaCl, i.v., n = 7), DOX group (DOX 5 mg /kg i.v., n = 23) and DOX+P group (DOX 5 mg/kg, i.v. plus P 10 mg/kg p.o. daily, beginning five days before DOX administration and during the follow-up period, n = 11). Rats' body weight and echocardiography parameters were monitored before and after drug/vehicle administration. Cardiac histology was performed post-mortem, as well as beta1-adrenergic receptor (ß1-AR), beta2-adrenergic receptor (ß2-AR), G protein-coupled receptor kinases type 2 (GRK2), type 3 (GRK3), beta-arrestin 1, and beta-arrestin 2 gene expression using RT-qPCR. DOX-treated rats exhibited bad general condition, adynamia, loss of body weight, and low survival. Echocardiography revealed two phenotypes: cardiomyopathy with left ventricular (LV) hypertrophy (DOX-HCM) and cardiomyopathy with LV dilation (DOX-DCM). In DOX-HCM rats only, there was an increased GRK2 and GRK3 gene expression and synthesis. DOX+P co-treated rats exhibited good general condition, normal spontaneous behaviour, gained weight over time, had increased survival, and preserved LV morphology and contractility. In these rats, gene expression and synthesis of GRK2 and GRK3 were decreased, while ß1-AR and ß2-AR were increased. Present results show for the first time that P effectively reduces DOX-induced cardiotoxicity and enhances survival.

Acute Peripheral Facial Nerve Palsy in Children and Adolescents: Clinical Aspects and Treatment Modalities.

BACKGROUND: Peripheral facial nerve palsy is a relatively frequent, rather idiopathic, and isolated nonprogressive disorder with a tendency toward spontaneous recovery in children. It is primarily characterized by unilateral paresis or paralysis of the mimic musculature affecting verbal communication, social interactions, and quality of life. OBJECTIVE: This study aimed to evaluate the clinical aspects and efficacy of different therapeutic modalities in the population of children and adolescents with acute peripheral facial nerve palsy, the quality and recovery rate in comparison to different therapy modalities and etiological factors as well as to determine parameters of recovery according to the age of patients. METHODS: The retrospective study included children and adolescents (n=129) with an acute onset of peripheral facial nerve palsy, diagnosed and treated in the Clinic of Neurology and Psychiatry for Children and Youth in Belgrade (2000-2018). The mean age of the patients was 11.53 years (SD±4.41). Gender distribution: 56.6% female and 43.4% male patients. RESULTS: There were 118 (91.5%) patients with partial and 11 (8.5%) patients with complete paralysis. Left-sided palsy occurred in 67 (51.9%) patients, right-sided in 58 (45.0%), while there were 4 (3.1%) bilateral paralyses. The most common etiological factor was idiopathic (Bell's palsy) - 74 (57.4%) patients followed by middle ear infections - 16 (12.4%). Regardless of etiology, age, and therapy protocols, there was a significant recovery in most of the patients (p<0.001), without significant differences in recovery rate. Comparison of inpatient and outpatient populations showed significant differences regarding the number of relapses, severity of clinical presentation, and recovery rate in relation to etiology. CONCLUSION: Bell's palsy is shown to be the most common cause of peripheral facial nerve palsy in children and adolescents, regardless of gender. It is followed by mid-ear infections, respiratory infections, and exposure to cold. Most children and adolescents recovered in three weeks after initial presentation, regardless of etiology, age, and therapy.

Baseline temperature in an animal model of schizophrenia: long-term effects of perinatal phencyclidine administration.

Phencyclidine (PCP), a dissociative anaesthetic, acts as a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist. PCP is a psychostimulant capable of producing both positive and negative symptoms of schizophrenia, including cognitive dysfunction in normal humans. Perinatal phencyclidine administration to rats has been widely accepted as an animal model of schizophrenia. It has been known for a long time that schizophrenia patients may develop various thermoregulatory disturbances. The aim of this study was to assess the acute effects of phencyclidine administration on the temperature of newborn rats, the long-term effects on the baseline temperature of perinatal phencyclidine administration and the effects of a PCP challenge on the temperature of adult perinatally treated rats. The animals were treated on the 2nd, 6th, 9th and 12th postnatal (PN) days with either phencyclidine (10 mg/kg) or saline. The interscapular skin temperature was measured during the first 40 postnatal days and subsequently the colonic temperature until PN day 62. The immediate effect of phencyclidine administration to pups was a significant decrease of the body temperature, while the application of PCP to adult rats perinatally treated with either saline or PCP caused a significant increase of the baseline temperature. Perinatal phencyclidine administration to rat pups produced a long lasting effect on the baseline temperature. It can be concluded that the nature of the response to acute phencyclidine administration differs between newborn and adult rats. Further experiments are necessary in order to clarify the role of specific neurotransmitter systems in the changes of temperature regulation provoked by phencyclidine administration.

Older age at the time of liver biopsy is the important risk factor for advanced fibrosis in patients with chronic hepatitis C.

BACKGROUND/AIMS: Progression of chronic hepatitis C depends on the host and viral characteristics, duration of infection, co-infection with other viruses, etc. In this study, some of demographic, epidemiological and viral data as risk factors for a degree of liver fibrosis were evaluated. METHODOLOGY: A total of 144 patients was investigated (89 males, ages from 16-65 years) classified into two groups, with fibrosis scores 0-3 and 4-6, using the Ishak scoring system. Significant variables were entered into univariate logistic regression model and further multivariate analysis was performed. RESULTS: There were 64% and 36% of patients with fibrosis scores 0-3 and 4-6, respectively. Gender, moderate to heavy alcohol abuse and high viral RNA were equally distributed between both groups. In univariate analysis, the age older than 40, history of intravenous drug abuse, and the genotype 1b were independently associated with different fibrosis scores. Multivariate regression analysis revealed ages older than 40 as the positive (p < 0.001), and younger than 40 as the negative predictive factors for fibrosis scores 4-6 and 0-3 (p < 0.001), respectively. CONCLUSIONS: Our results indicate the age over 40 at the time of liver biopsy as the important risk factor for advanced liver disease in chronic hepatitis C according to fibrosis scores.

Homocysteine serum levels and MTHFR C677T genotype in patients with Parkinson's disease, with and without levodopa therapy.

Both methylenetetrahydrofolate (MTHFR) C677T genotype and levodopa treatment may give rise to elevated serum homocysteine levels in parkinsonian patients. We aimed to clarify the interplay of these factors in pathogenesis of Parkinson's disease (PD)-related hyperhomocysteinemia. Total serum levels of homocysteine (tHcy) and MTHFR C677T genotype were investigated in levodopa-treated and -untreated parkinsonian ("de novo") patients, as well as in control healthy subjects matched by age and gender (N=83, 30 and 53, respectively). MTHFR C677T genotypes were equally distributed in PD patients and control subjects, the T allele homozygosity being observed in app. 12-17% cases. tHcy concentrations were significantly higher in both levodopa-treated and -untreated PD patients than in control subjects, and in TT homozygotes than in CT or CC genotype carriers. tHcy levels significantly correlated with the duration of the disease in PD treated patients only, reaching the maximum after 3-6 years. However, there was no correlation between tHcy levels and total daily intake of levodopa in the same group of PD patients. In conclusion, MTHFR C677T genotype is a significant factor for hyperhomocysteinemia in patients with PD, levodopa-untreated and probably even more in levodopa-treated PD patients.

Oral teicoplanin for successful treatment of severe refractory Clostridium difficile infection.

INTRODUCTION: Clostridium difficile is the leading cause of hospital-acquired diarrhoea. There is no defined protocol for treating severe Clostridium difficile infection (CDI) refractory to vancomycin or vancomycin and metronidazole combination therapy. The aim of this study was to evaluate the rate of clinical cure, time to resolution of diarrhoea and recurrence rate in patients with severe refractory CDI treated with oral teicoplanin. METHODOLOGY: A one-year prospective study was carried out in the Clinic for Infectious and Tropical Diseases, Clinical Center Serbia. Patients with severe and complicated CDI who failed to respond to oral vancomycin and intravenous metronidazole combination therapy were enrolled. They were given oral teicoplanin 100 mg bi-daily. Patients were followed for recurrence for eight weeks. RESULTS: Nine patients with a mean age of 70.8±9.4 years were analyzed. All patients had pseudomembranous colitis, and five had complicated disease. In four patients intracolonic delivery of vancomycin was also performed in addition to oral vancomycin and intravenous metronidazole prior to initiating teicoplanin, but without improvement. After teicoplanin initiation all patients achieved clinical cure. The mean time to resolution of diarrhoea after teicoplanin introduction was 6.3±4.5 days. There was no statistically significant difference in time to resolution of diarrhoea according to initial leucocyte count, age over 65 years, the presence of ileus, complicated disease and the use of concomitant antibiotic therapy (p = 0.652, 0,652, 0.374, 0.374, and 0,548, respectively). None of the patients experienced recurrence. CONCLUSIONS: Oral teicoplanin might be a potential treatment for severe and complicated refractory CDI, but further studies are required.

Incidence, predictors and prognostic implications of bleeding complicating primary percutaneous coronary intervention.

BACKGROUND/AIM: Data about bleeding complicating primary percutaneous coronary intervention (PCI) are more frequently obtained from randomized clinical trials on patients with acute coronary syndromes (ACS), but less frequently from surveys or registries on patients with ST-elevation myocardial infarction (STEMI). The aim of this study was to investigate the incidence, predictors and prognostic impact of in-hospital major bleeding in the population of unselected real-world patients with acute STEMI undergoing primary PCI. METHODS: All consecutive patients presenting with STEMI who underwent primary PCI at a single large tertiary healthcare center between January 2005 and July 2009, were studied. Major bleeding was defined according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) study criteria. We examined the association between in-hospital major bleeding and death or major adverse cardiac events (MACE) in patients treated with PCI. The primary outcomes were in-hospital and 6-month mortality and MACE. RESULTS: Of the 770 STEMI patients treated with primary PCI, in-hospital major bleeding occurred in 32 (4.2%) patients. Independent pre-dictors of major bleeding were advanced age (≥ 65 years), female gender, baseline anemia and elevated white blood cell (WBC) count and signs of congestive heart failure at admission (Killip class II-IV). In-hospital and 6 month mortality and MACE, rates were more than 2.5-fold-higher in patients who developed major bleeding compared with those who did not. Major bleeding was predictor of 6-month MACE, independent of a few risk factors (previous MI, previous PCI, diabetes mellitus and hypertension); (OR = 3.02; 95% CI for OR 1.20-7.61; p = 0.019) but was not a true independent predictor of MACE and mortality in the fully adjusted models. CONCLUSION: Patients of advanced age, female gender, with baseline anemia and elevated WBC count and those with Killip class II-IV at presentation are at particularly high risk of bleeding after primary PCI. Bleeding is associated with adverse outcome and may be an important marker of patient frailty, but it is not a true independent predictor of mortality/MACE.

Characteristics of patients dying from acute viral hepatitis in Serbia.

BACKGROUND/AIMS: Acute viral hepatitis is complicated rarely with severe liver failure due to many factors associated with the etiology, patient age, and time of development of hepatic encephalopathy, etc. The aim of this study was to identify some of the clinical and laboratory features associated with a fatal outcome in patients dying from acute viral hepatitis in Serbia. METHODS: Clinical and laboratory data from 47 patients hospitalized from January 1989 December 2006 were reviewed retrospectively. Serological tests for hepatitis A, B, C, D, and E viruses, herpes simplex viruses, cytomegalovirus, and Epstein-Barr virus were done. Histological features were assessed from 35 liver tissues. The electronic base, SPSS for Windows (version 11.0), was used for statistical analysis. RESULTS: The majority of the patients had alanine aminotransferase (ALT) >20x the normal value, serum bilirubin >300 µmol/L, prothrombin time >25 seconds (s), and white blood cell count >12 x 10(9)/L. Regression analysis revealed activity of alanine aminotransferase >20x the normal value to be associated with fulminant (p=0.015) and serum bilirubin concentration with subfulminant hepatitis (p=0.008). Hepatitis B virus was the most commonly detected virus (70%). Massive hepatocyte necrosis vs. sub-massive with bridging necrosis were found to be independent of clinical presentation. CONCLUSIONS: Hepatitis B virus infection, severe impairment of liver function tests, and confluent hepatocyte necrosis and infection characterize patients dying from acute viral hepatitis in Serbia. High activity of alanine aminotransferase reflects rapid and extensive acute viral liver injury, while deep jaundice is more common in a protracted course of the disease.

Treatment of subacute hepatitis B with lamivudine: a pilot study in Serbia.

BACKGROUND/AIM: The incidence of acute hepatitis B viral (HBV) infection in adults has increased in recent years in Serbia. Most icteric patients with acute hepatitis B resolve their infection and do not require treatment. Fulminant hepatitis B is a severe form of acute infection complicated by encephalopathy and liver failure. Subgroups of fulminant hepatitis B including hyperacute, acute and subacute are defined by the interval between jaundice and encephalopathy. Fulminant hepatic failure or subacute hepatitis B infection we observed in about 1% of all cases. In cases of fulminant hepatic failure or subacute form of HBV infection orthotopic liver transplantation can be life-saving operation, but in our country this procedure is difficult to achieve. Lamivudine has been established as a safe and effective antiviral agent for the treatment of chronic HBV hepatitis. METHODS: In our pilot study performed at the Institute of Infectious and Tropical Diseases in Belgrade, Serbia in the period between 2002 and 2006 we treated 10 patients with clinically verified subacute HBV infection with lamivudine, 100 mg orally per day. RESULTS: The most of the treated patients (9/10; 90%) survived subacute form of hepatitis B. After a few weeks of the treatment serum aminotransferase levels and other liver-function tests were normalized. Also, after a four-month lamivudine treatment all the patients lost HBsAg. Lamivudine was discontinued after six months in all the patients. In addition, six months after lamivudine was discontinued the patients remained well with normal results on liver-function tests. CONCLUSION: The obtained results suggest significant efficacy of lamivudine in patients with subacute hepatitis B. Also, we suggest that lamivudine therapy should be administered early in progression of subacute disease since it could be life-saving treatment in some patients, especially in the countries (like Serbia) where orthotopic liver transplantation is difficult to achieve.

Acute protective effects of simvastatin in the rat model of renal ischemia-reperfusion injury: it is never too late for the pretreatment.

Acute pretreatment with a single i.v. bolus injection of simvastatin (1 mg/kg) significantly protects rat kidney injured by ischemia-reperfusion (I/R) (45 min + 6 h). We aimed to determine the optimal timing of such a pretreatment. The effects of both injections of simvastatin before ischemia and reperfusion were similar regarding total histological score. However, simvastatin injected 30 min before ischemia was 30% - 75% more effective in reduction of serum creatinine levels and interstitial edema score, while its injections 5 and 30 min before reperfusion were 25% - 60% more effective in reduction of tubular necrosis score and fractional excretion of Na+. However, the observed differences do not seem to offer significant advantage in clinical settings.

Pattern of utilization of benzodiazepines in patients with hypertension: a pilot study.

BACKGROUND/AIM: The analysis of drug prescribing in general practice in Serbia showed that the use of benzodiazepines is most frequently associated with hypertension. The aim of this study was to establish the correlation of the characteristics of patients with hypertension to antihypertensive drug therapy, and the intake of benzodiazepines. METHODS: A special questionnaire was used for interviewing the patients (n = 171) chronically treated for hypertenson. Statistical tests used were chi2-test and Student's t-test. RESULTS: No differences were noted in terms of age, gender, education, body weight, smoking habits and blood pressure (155 +/- 4.9/100 +/- 2.7 mmHg vs. 160 +/- 2.2/105 +/- 3.7 mmHg), between the group I (antihypertensive drugs+benzodiazepines: n = 79), and the group II (antihypertensives only: n = 92). The patients taking benzodiazepines received a lower number of different antihypertensive drugs (2.3 +/- 0.09 vs. 2.7 +/- 0.10; p < 0.01), but the total antihypertensive drug load was significantly greater than in the group II (2.6 +/- 0.10 vs. 1.9 +/- 0.15 defined daily doses (DDD)/patient/day; p < 0.01). Benzodiazepines were taken for anxiety (62%) and hypertension (21%), rarely for insomnia, mostly once a day, at bedtime. About half the patients took benzodiazepines regularly for months or years aware of the risk for addiction. Diazepam was used by 82% of the patients. The average daily exposure to benzodiazepines was 0.45 +/- 0.05 DDD/patient/day. The drug was bought without prescription in 25% of the patients, and without consulting a physician in 12% of them. CONCLUSION: The study confirmed a close association of hypertension with the use of benzodiazepines. The frequent use of benzodiazepines in the patients with hypertension might be caused by an inadequate response to antihypertensive drug therapy, besides anxiety and insomnia. The therapeutic efficacy of a long-term use of low doses of benzodiazepines in hypertension requires further investigation.

Type of electrical stimulation influences diaphragm response to adrenoceptor and calcium channel modulators: the role of extracellular and intracellular calcium events.

The influence of direct single pulse and subtetanic electrical stimulation (ES) on isolated rat hemidiaphragm response to adrenoceptor antagonists and calcium channel blockers was investigated. Muscle contractility was stimulated by cumulative micromolar noradrenaline. Noradrenaline effects on developed tension (Td) in the presence of various alpha- and beta-adrenoceptor antagonists (e.g., prazosin and ICI 118551) were qualitatively different during different types of ES. Also, intact L-voltage calcium channels were necessary for noradrenaline-induced potentiation of Td during both types of ES, while the balance between ryanodine receptors- and inositol triphosphate (IP3)-related calcium events in the muscle was influenced by the pattern of the ES.

[Effects of new nitric oxide synthase inhibitors on spontaneous locomotor activity].

INTRODUCTION: New nitric oxide synthase (NOS) inhibitors: 3-bromo-7-nitroindazole (3-Br-7-NI), 1-(2-trifluoromethylphenyl) imidazole (TRIM), S-methyl-L-thiocitrulline (S-Me-TC) and 7-nitroindazole (7-NI) reduce spontaneous locomotor activity in mice. MATERIAL AND METHODS: In order to elucidate central effects of NOS inhibitors on locomotor activity, the influence of 7-NI on electroencephalographic (EEG) power spectrum in rats was investigated. RESULTS: 7-NI reduced the EEG power density in all frequency bands in rats, suggesting a depression of the central neuronal activity. The electrophysiologic power was most reduced in the range of 7-9 Hz of the rhythmic slow activity (theta rhythm), which is in accordance with decreased locomotor activity observed following administration of NOS inhibitors. CONCLUSION: The present results indicate that nitric oxide exerts an excitatory effect on central neuronal structures involved in regulation of locomotion.

[Chronic hepatitis C virus infection: is there a correlation between HCV genotypes and the level of viremia?].

INTRODUCTION: Hepatitis C virus (HCV) RNA status and HCV genotypes have become extremely important for exact diagnosis, prognosis, duration of treatment and monitoring of antiviral therapy of chronic HCV infection. MATERIAL AND METHODS: For the purpose of precise and objective assessment of virologic analyses, such as the determination of the number of virus copies and virus genotypes, 110 patients with chronic HCV infection were tested Genotyping of HCV isolates and HCV RNA quantification were performed by using the PCR method. Genotype 1b infection was verified in 49.1% of patients, genotype 3a infection was found in 28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections were diagnosed in 9.1% of cases. RESULTS: Patients infected by genotype 1b had significantly higher serum HCV RNA level in relation to patients infected by other genotypes (p < 0.05). Over 70% of patients infected by genotype 1b had more than 2 x 10(6) virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately 7.7 x 10(6) virus copies in 1 ml of blood, which was significantly higher in comparison with female patients (2.3 x 10(6) copies/ml; p < 0.05). CONCLUSION: Our results are in concordance with the results of other authors reporting that genotype 1b is predominant in Europe, as well as significantly higher incidence of viremia in patients with genotype 1b infection in relation to other HCV genotypes. Based on these results, we can conclude that our patients, most commonly, present with severe clinical course of chronic HCV infection and require longer treatment (48 weeks), which causes economic problems.

Histopathology of chronic hepatitis C in relation to virus genotype.

BACKGROUND/AIM: The natural history of hepatitis C virus (HCV) infection is variable and the factors determining the course of the illness are unclear. There are geographical variations in the distribution of different HCV genotypes, and some of them are related to the specific infection routes. Regarding our country, the dominant genotype is genotype 1b. It is unclear and still remains a question whether the distinct histopathological manifestations are related to the particular genotypes of HCV. Thus, the aim of this study was to determine whether the distinct histopathological manifestations of HCV infection might be in relation to the individual virus genotype. METHODS: In this study we examined 126 patients with chronic HCV infection regarding the histopathological features, demographic data, and virus genotype. The observed groups of patients were predominantly infected with HCV genotypes 1b and 3a. RESULTS: In this study we found that the patients infected with HCV genotype 1b had more frequently moderate or severe necroinflammatory activity of the disease, significantly higher grading score as compared with other genotypes (p < 0.0001). A higher degree of fibrosis was, also, more common in the patients infected with genotype 1b of HCV as compared with other genotypes (p < 0.05). There were no significant correlations between the necroinflammatory activity of the disease and the stage of fibrosis in 1b, 4 and mixed genotypes. CONCLUSION: The present data support the hypothesis that distinct genotypes of HCV are associated with the particular histopathological manifestation of the disease.

Single-dose intravenous simvastatin treatment attenuates renal injury in an experimental model of ischemia-reperfusion in the rat.

The effect of acute pretreatment with a single dose of simvastatin (1 mg/kg, i.v.; 30 min before ischemia) on renal dysfunction caused by ischemia-reperfusion (I/R) injury in the rat was investigated. I/R injury was induced by clamping both renal vascular pedicles for 45 min, followed by 4 h of reperfusion with saline (2 ml/kg per hour). Simvastatin significantly improved both parameters of glomerular and tubular dysfunction (e.g., creatinine levels and fractional excretion of Na(+), respectively) and especially improved the histological score, compared to control I/R-injured rats treated with saline or 10% DMSO only.

[Suicide by intravenous injection of rocuronium-bromide--case report].

Suicides by intravenous injection of an overdose of medicaments are uncommon. In this paper, we present the case of a suicide by rocuronium-bromide injection in combination with an oral overdose of metoprolol. Unfortunately, in Belgrade, there is no toxicological laboratory capable of detecting rocuronium. The interpretation of autopsy and toxicological data in this case was made difficult due to the extreme putrefaction of the body of the deceased. So, by forensic investigation, the case was solved indirectly, through circumstantial evidence: an empty ampoule of rocuronium found near the body, as well as a plastic syringe and cloth-bandage found in the left hand of the deceased.

Treatment of anicteric acute hepatitis C with peginterferon alpha-2a plus ribavirin.

BACKGROUND: Hepatitis C virus (HCV) infection is the most frequent cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world. Acute hepatitis C is the most commonly asymptomatic liver disease with the development of chronic HCV infection in the majority of infected patients. Studies of the natural history of HCV infection suggest that only 15-30% of patients with acute infection recover spontaneously. Others, up to 85% of the infected patients develop chronic hepatitis C. Acute hepatitis C is so uncommon and with the unpredictable occurrence, and of the low frequency, that it is difficult to determine the optimal treatment of this disease. There have been many randomized, controlled trials of the therapy in patients with chronic hepatitis C, but none of an adequate size or rigor in patients with acute hepatitis C. Therefore, the causal treatment of patients with acute hepatitis C aimed at the prevention of chronic liver disease is necessary. CASE REPORT: We have treated a patient with anicteric form of acute hepatitis C after a three-month outpatient follow-up using a combined therapy: pegylated interferon-alpha 2a, 180 microg, subcutaneously, once a week plus ribavirin 1000 mg orally once a day. The treatment lasted 24 weeks. Stable biochemical and virological response was achieved both at the end of the treatment and 6 months after the completion of the therapy. CONCLUSION: We believe that the above mentioned might be one of the approaches to the treatment of acute hepatitis C. However, further prospective studies with significantly larger number of patients are necessary for the definite conclusions about the treatment of HCV infections.