Prevalence and risk factor of renal dysfunction induced by bacterial infection other than spontaneous bacterial peritonitis in patients with cirrhosis.

BACKGROUND: Deterioration of renal function in cirrhotic patients with spontaneous bacterial peritonitis (SBP) is a predictor for inhospital mortality. However, the clinical significance of renal dysfunction during bacterial infection other than SBP is unknown. AIM: To investigate the prevalence and clinical significance of renal dysfunction due to bacterial infections other than SBP in patients with liver cirrhosis. METHODS: Retrospective data from in-patients with bacterial infections other than SBP were analyzed. RESULTS: Eighty-two patients were recruited for the analysis. Infection was located in urinary tract (41.5%), pneumonia (34.1%), biliary tract (3.7%), cellulitis (6.1%), gastrointestinal tract (4.9%) and bacteremia of unknown origin (9.7%). Renal dysfunction developed in 40 patients (48.8%), of which 13 patients had irreversible renal dysfunction. In the univariate and multivariate analysis, the initial MELD score, neutrophil count, bilirubin, and blood pressure were significant risk factors for renal dysfunction. CONCLUSION: The prevalence of renal dysfunction during bacterial infection other than SBP in patients with liver cirrhosis was 48.8%, and its development was related to the severity of the liver disease. Occurrence of irreversible renal dysfunction seemed to affect the prognosis of these patients.

[Abdominal tuberculosis: a retrospective series of 90 cases]. / Tuberculose abdominale : étude rétrospective de 90 cas.

PURPOSE: The aim of this study was to analyze the clinical, bacteriological, radiological and therapeutic features of abdominal tuberculosis in a series of 90 patients. METHODS: This was a retrospective and descriptive multicentre study of 90 cases of abdominal tuberculosis conducted from June 1997 to June 2008. Diagnosis of tuberculosis was based on bacteriologic evidence in 12 cases, histological evidence in 55 cases and on clinical and radiologic features with favorable outcomes under specific treatment in the 23 remaining cases. RESULTS: Thirty-one patients were male and 59 were female. The mean age of the patients was 41.5 years. Family history of tuberculosis was reported in three cases. Associated risk factors were: diabetes mellitus (five cases), ethylism (one case), post-hepatitis C cirrhosis (one case), systemic lupus erythematosus treated by corticosteroids (one case). Sites of involvement were: peritoneum (78 cases), liver (14 cases), gut (nine cases) and spleen (eight cases). Forty-eight patients (53,3%) had only an abdominal involvement, nine others patients (10%) had an abdominal involvement associated with intra-abdominal lymph nodes, 16 patients (17,8%) had a respiratory involvement (pulmonary, pleural and mediastinal lymph nodes), eight patients (8,8%) presented with an extra-abdominal and extra-respiratory involvement and 10 patients (11,1%) had respiratory and extra-respiratory disease associated with abdominal involvement. Among the 54 patients who underwent laparoscopy or laparotomy, diagnosis was evoked on macroscopic examination in 51. CONCLUSION: Laparoscopy and laparotomy are still helpful for the diagnosis of abdominal tuberculosis, especially in the presence of peritoneal involvement.

Association of chemokine and chemokine receptor polymorphisms with activity degree of IBD in Tunisian patients.

Crohn's disease (CD) and ulcerative colitis (UC) have complex genetic background that is characterised by more than one susceptibility locus. To detect a possible association between the functional polymorphisms of the chemokine receptors CCR5, CCR2 and MCP-1 genes and susceptibility to CD and UC in Tunisian population, polymorphisms of CCR5-delta32, CCR5-59029-A/G, CCR2-V641 and MCP-1-2518-G/A were analysed in 194 Inflammatory bowel disease (IBD) patients and 169 healthy blood donors using PCR-RFLP and PCR-SSP methods. The patients were classified in 126 patients with CD and 68 patients with UC. The genotypic and allelic frequencies of all polymorphisms studied, did not reveal significant differences between patients and conrols and among CD and UC patients. However, analysis of CD patients revealed that those without homozygosous G/G genotype are more frequently in remission compared to those with this genotype (OR: 0.4, 95% CI: [0.174-0.928]; p = 0.03). Also, the frequency of the CCR2-641 muted allele was statistically higher in CD patients in remission disease than those in active form (OR: 0.267 95% CI: [0.09-0.78]; p = 0.01). Adjustment for known covariates factors (age, gender and immunosuppressive regimen) confirmed these univariate findings and revealed that the CCR5-59029-A/G and CCR2-V64I genotype were associated to remission form of CD (OR: 263; 95% CI: [1.01-6.80]; p = 0.047 and OR: 4.64; 95% CI: [1.01-21.31]; p = 0.049 respectively). In conclusion, the present study supports the involvement of chemokine receptor (CCR2 and CCR5) polymorphisms in activity degree of the IBD disease in Tunisian patients.

Diffuse primary malignant melanoma of the upper gastrointestinal tract.

Primary malignant melanomas of the GI tract are very rare. Their symptomatology is not specific. We report a 78-year-old Tunisian woman hospitalised with a 6-month history of recurrent abdominal pain, loss of appetite, weakness and weight loss. She had no personal history of cutaneous or ocular melanoma. Upper gastrointestinal endoscopy revealed multiple small, raised darkly pigmented tumours. Theses lesions were found in the oesophagus, the stomach, the bulb and the duodenum. Biopsy specimens were taken and histology showed the presence of melanocytic cells with abundant melanin pigment. Immunohistochemically, tumour cells were positive for HMB-45. Morphological examinations revealed hepatomegaly with multiple nodules with small lymph nodes at the celiac axis. All available diagnostic procedures failed to identify any other site of ocular or cutaneous melanoma, the present case was considered as primary GI melanoma. Palliative chemotherapy was not possible because patient was extremely cachectic and she died one month later.

Seroprevalence of Helicobacter pylori among Tunisian blood donors (outpatients), symptomatic patients and control subjects.

OBJECTIVES: Helicobacter pylori is a worldwide infection, although little data are available in the Tunisian population. The aims of our study were to detect the prevalence of H. pylori in a blood-donor population (n=250) and in another population of hospital-consulting patients comprising 87 symptomatic patients and 59 controls, and to determine the factors that influence the prevalence. MATERIALS AND METHODS: Study subjects answered a standardized questionnaire, and IgG anti-H. pylori and anti-cag were detected by ELISA. In the second population, culture and cagA polymerase chain reaction were performed. RESULTS: The seroprevalence of H. pylori in blood donors was 64%, and 11% had anti-cag. All patients positive for anti-cag were also positive for anti-H. pylori antibodies. The seroprevalence of H. pylori was 99.3% in the hospital-consulting patients, of whom 55.5% were positive for anti-cag. The difference between the anti-cag and symptomatic patients (66.7%) and controls (39%) was significant. Symptomatic patients had a higher rate of anti-cag (66.7%) compared with the controls (39%) and blood donors (11%). CONCLUSION: H. pylori seroprevalence in blood donors is low (64%) compared with symptomatic patients (99.3%), and anti-cag was statistically associated with symptomatic patients and pathology. Also, some environmental factors were correlated with H. pylori seroprevalence.

Cerebral venous sinus thrombosis as presenting feature of ulcerative colitis.

Thrombosis is a well recognized complication of inflammatory bowel disease that occurs in 1.3 to 6.4% of patients, however, cerebral vascular involvement is unusual. We present the case of a 16-year-old female in whom cerebral venous thrombosis was the presenting symptom of an active ulcerative pancolitis. Thrombophilia screen (plasma levels of proteins C and S, antithrombin, antibeta2-glycoprotein, lupus anticoagulant and anticardiolipin antibodies, activated protein C resistance, homocystein level antinuclear antibodies) was negative. The patient was successfully treated with anticoagulant therapy, phenobarbital and sulfasalazine. Cerebral venous thrombosis is an exceptional presenting feature of ulcerative colitis. Disease activity may play a major role in the occurrence of thrombosis.

[Ulcerative colitis and schizophrenia: fortuitous association or etiopathogenic link?]. / Rectocolite hemorragique et schizophrenie: association fortuite ou lien etiopathogenique?

BACKGROUND: Ulcerative colitis is a chronic inflammatory bowel disease with multiple pathogenic factors. Psychiatric disorder have frequently been associated to ulcerative colitis, the most frequent being depression and anxiety, whereas schizophrenia is unusual. AIM: Report a new case of ulcerative colitis associated topsychiatric disorder. CASE-REPORT: We report the case of a 42-year-old woman with ulcerative colitis associated with schizophrenia. Although the two diagnoses were concomitant, on questioning, she revealed that digestive symptoms began before psychiatric disorders. CONCLUSION: Few cases of schizophrenia associated with ulcerative colitis have been reported in the literature. We discuss epidemiological, etiopathogenic and therapeutic links between the two diseases.

No evidence of the APC D1822V missense variant's pathogenicity in Tunisian patients with sporadic colorectal cancer.

OBJECTIVES: Sporadic colorectal cancer is influenced by numerous single nucleotide polymorphisms (SNPs), each with minor effects on the cancer risk. This study seeks to determine whether there is any association of the I1307K, E1317Q and D1822V variants within the Adenomatous polyposis coli gene (APC) and risk to develop colorectal cancer in Tunisian population. METHODS: Direct sequencing was used to investigate three SNPs in the APC in 48 Tunisian sporadic colorectal cancer cases and 63 controls. RESULTS: There was no statistically significant association between the I1307K, E1317Q and D1822V variants investigated and colorectal cancer risk. CONCLUSION: The lack of association may show that these variants selected for this study are not involved in the colorectal carcinogenic process. Otherwise, the eventual biological effect is so little to go undetected, unless increasing the sample size.

[Chronic viral C hepatitis associated with primary biliary cirrhosis. Report of two cases]. / Association hépatite chronique virale C et cirrhose biliaire primitive. A propos de deux observations.

Chronic viral hepatitis C is often associated with various autoimmune disorders. We report two patients infected by genotype 1b hepatitis C virus associated with primary biliary cirrhosis. These patients had anicteric cholestasis associated with cytolysis and positivity of M2 antimitochondrial antibodies at a titre of 1/200. Liver biopsy revealed chronic hepatitis in one case and histological pattern of primary biliary cirrhosis in the other. One patient was treated by antiviral therapy; the other only by ursodesoxycholic acid because of the association with hemolytic anemia. Association between primary biliary cirrhosis and chronic viral hepatitis C is uncommon and associated with diagnostic and therapeutic challenges.

Disposition of amiodarone in rats after single and multiple intraperitoneal doses.

The pharmacokinetics of amiodarone was studied after single and multiple dosing in two groups of male Wistar and Albino rats. The first group (40 rats) received a single intraperitoneal (i.p.) dose of amiodarone (100 mg/kg) and 4 rats sacrificed 1, 2, 4, 6, 12, 18, 24, 36, 48 and 72 hours post dosing. The second group (42 rats) received amiodarone (50 mg/kg, i.p. daily) for 5 days a week for 5 weeks and 6 rats were sacrificed at 1, 2, 3, 4, 5, 6 and 8 weeks. Rats of both groups were sampled for blood, heart, lung and fat and the concentrations of amiodarone in these samples were determined using High Performance Liquid Chromatography (HPLC). The elimination of amiodarone from plasma after single dose followed a biphasic pattern with a terminal half-life of 54.7+/-8.2 hours. The concentrations of amiodarone in the tissues were halved within 26.8, 34.9 and 37.45 hours in the heart, lung and fat, respectively. The average concentrations of amiodarone in plasma, heart, lung and fat after single dose were 1.24 microg/ml, 1.73 microg/mg and 29.01 microg/mg, respectivelly. The concentrations of amiodarone after multiple dosing were halved within 8.4, 5.5, 6.4 and 9.8 days, for the plasma, heart, lung and fat, respectively. The average concentrations of amiodarone in plasma, heart, lung and fat during multiple doses were 0.97 microg/ml, 1.41 microg/mg, 7.63 microg/mg and 65.01 microg/mg respectively. In conclusion, after multiple dosing, the elimination half-life of amiodarone and its fat contents were 3.7 and 2.8 times greater than that after single dosing. The excessive amount of amiodarone observed in fat tissues after multiple dosing is probably the reason for the prolonged elimination half-life. Based on the elimination half-lives data, the time to steady state is about two weeks and the drug should be withheld for less than a month if a patient required discontinuation because of serious adverse effects.

The preventive role of deferoxamine against acute doxorubicin-induced cardiac, renal and hepatic toxicity in rats.

The iron chelating activity of deferoxamine (DFO) has been exploited to obtain protection against the peroxidative damage in rat heart which was induced by the administration of an acute dose of doxorubicin (DXR, 25 mg x kg(-1), i.v.). The peroxidative lesions were evaluated both biochemically and histopathologically, 48 h after DXR administration. Abnormal biochemical changes including a marked increase in the levels of serum creatine kinase isoenzyme (CK-MB), and lactate dehydrogenase (LDH), as well as elevated serum creatinine, blood urea nitrogen and transaminases (ALT and AST) levels were observed. Myocardial tissue from DXR treated rats showed a marked increase in malondialdehyde (MDA) production and depletion of reduced glutathione (GSH) contents. Similar results were also observed in both kidney and liver tissues. Pretreatment of rats with DFO, given i.p. 30 min prior to DXR injection, substantially reduced the peroxidative damage in the myocardium, hepatic and renal tissues and markedly lowered the serum CK-MB, LDH and the other biochemical variables. The protective effects obtained by DFO administration, however, were not complete and did not reach those of the control group. The significant protection against DXR-induced cardiomyopathy by DFO was evident from the histopathological findings observed by light microscopy. DFO at a dosing level equivalent to 10-fold of that of DXR was useful to obtain protective effects. Higher DFO dosing levels did not, however, show more improvement in the DXR-induced cardiotoxicity and at the same time exhibited hepatoxicity which was confirmed by microscopical examination. These results strongly suggest that DFO protects against acute DXR-induced cardiotoxicity in a dose-dependent manner with recognizing the presence of mild DFO-related biochemical and cytological hepatic toxicity.

Effects of gemcitabine on cisplatin-induced nephrotoxicity in rats: schedule-dependent study.

The effects of gemcitabine (dFdC) on the lipid peroxidation and kidney histopathology in the nephrotoxicity of an antitumour drug cisplatin (CDDP) were studied in rats. dFdC was administered intraperitoneally (i.p.) at single doses of 90 mgkg(-1) while CDDP was administered i.p. at single doses of 6 mgkg(-1). Both drugs were injected either alone or sequentially in combination. In one case, CDDP preceded dFdC by 4 h and 24 h and in the other case, dFdC preceded CDDP by 4 h and 24 h. Seven days after CDDP administration, the nephrotoxicity was manifested biochemically by elevation of serum creatinine, blood urea nitrogen and an increase in the kidney weight as a percentage of total body weight. In addition, marked decreases in serum albumin and calcium levels were observed. Lipid peroxidation in the kidney was monitored by measuring the malondialdehyde (MDA) production level and kidney glutathione (GSH) content, which were increased and depleted, respectively. Administration of dFdC 4 h and 24 h after CDDP administration did not significantly change the indices of CDDP-induced nephrotoxicity or the kidney platinum concentration levels in comparison with those animals treated with CDDP alone. On the contrary, administration of dFdC 4 h and 24 h prior to CDDP administration significantly aggravated CDDP-induced nephrotoxicity which was manifested by severe increases in the serum creatinine and blood urea nitrogen levels as well as kidney weight as a percentage of total body weight. In addition, kidney tissue showed severe GSH depletion and increases in the MDA production and platinum concentration levels. Moreover, treatment of rats with dFdC 24 h prior to CDDP resulted in much more aggravation of CDDP-induced nephrotoxicity in comparison with those animals treated with dFdC 4 h prior to CDDP. Histopathological examination demonstrated tubular atrophy, tubular necrosis and drug-induced nuclear changes in the CDDP-treated group. However, pretreatment of rats with dFdC 4 h and 24 h prior to CDDP revealed extensive interstitial nephritis, renal tubular atrophy and tubular necrosis with 'sloughing off' of the lining cells, especially with those rats treated with dFdC 24 h prior to CDDP. These results might suggest that administration of dFdC prior to CDDP enhanced the lipid peroxidation in kidney tissue and aggravated CDDP-induced nephrotoxicity.

Cisplatin pharmacokinetics and its nephrotoxicity in diabetic rabbits.

BACKGROUND: This study was designed to investigate the relationship between the attenuation of cisplatin (CDDP)-induced nephrotoxicity in experimental diabetic rabbits and the plasma pharmacokinetics of the free ultrafilterable and total plasma platinum (Pt) levels. METHODS: Two groups of age-matched male New Zealand white rabbits were used; the first group consisted of rabbits with streptozotocin-induced diabetes (single i.v. bolus dose of streptozotocin of 65 mg/kg in citrate buffer, pH 4.6), and the second group of nondiabetic rabbits treated with the same volume of citrate buffer. Both groups were treated with CDDP (5 mg/kg, single i.v. bolus dose) 3 days after induction of the diabetic state in the first group. The plasma Pt levels were followed for 4 h after CDDP administration, in which the free ultrafilterable and total plasma Pt concentrations were determined by atomic absorption spectrometry. The pharmacokinetic parameters of free ultrafilterable plasma Pt were determined using a noncompartment pharmacokinetic model of analysis. RESULTS: The total plasma Pt levels declined in a biphasic manner and were adequately described by a two-compartment model. No significant change was observed in the pharmacokinetics of either the free ultrafilterable or total plasma Pt levels in the diabetic group in comparison with the control nondiabetic group (p > 0.05). However, 4 h after CDDP administration, the total plasma Pt level of the nondiabetic group was significantly higher than that of the diabetic rabbits (p < 0.001). Indices of nephrotoxicity were determined 7 days after CDDP administration. The results revealed that the diabetic state protected against CDDP-induced nephrotoxicity. The nondiabetic rabbits exhibited highly significant elevations in the serum creatinine and urea levels and a decrease in the serum albumin level (p < 0.001) in comparison with the diabetic group. CONCLUSIONS: These findings might suggest that the reduction in CDDP-induced nephrotoxicity in diabetic rabbits is not due to a change in the plasma pharmacokinetic profile within the drug follow-up period. It could be anticipated that the rapid decline in the total plasma Pt level after CDDP administration to diabetic rabbits, as well as the reduction in the terminal elimination half-life of the total plasma Pt level might be responsible for the reduction in CDDP-induced nephrotoxicity. Also, alterations in the how kidneys of diabetics deal with the renal excretion of Pt and reduction of its accumulation in kidney tissue are not excluded.

[Vaccination against viral hepatitis B for public health personnel: the case of the National Fund of Social Security]. / La vaccination contre l'hépatite virale B pour le personnel de sante: le cas de la Caisse Nationale de Securite Sociale (CNSS).

Viral hepatitis B is endemic in Tunisia at an intermediate level. Health professional are a group particularly exposed to the infection. Immunization is the most efficient way to prevent this disease. In this study, we had try to estimate the cost of three strategies of immunization: immunization after a complete serology, immunization after a sequencial serology and immunization without previous serology. The study was conducted at the clinic of the National Fund of Social Security in El Khadra. All the personal of the clinic was invited to participate to a program of immunization after complete serology. Participation rate was at 93.8%. 33.3% of the personal was immunized (24% by a previous contact with the virus and 9.9% by a previous immunization). The costs of the three strategies were as below: immunization after complete serology: 53.4 tunisian dinars by person. immunization after sequantial serology: 33.06 tunisian dinars by person. immunization without serology: 16.2 tunisian dinars by person. Immunization without previous serology has the lower cost, and doesn't expose at any sid effect. However, a post immunization serology vaccinal should be desirable.

The effect of rebamipide on cisplatin-induced nephrotoxicity in rats.

This study aimed to evaluate the protective effect of rebamipide (free radical scavenger) against the nephrotoxic effect induced by cisplatin in normal rats. Twenty-four male Wister albino rats were divided equally into four groups: control, rebamipide, cisplatin and cisplatin plus rebamipide-treated groups. Nephrotoxicity was induced with single intravenous (i.v.) cisplatin dose of 6 mg kg(-1)and measured through the estimation of kidney weight, serum albumin (Alb), serum creatinine (Cr), blood urea nitrogen (BUN), kidney glutathione (GSH) and malondialdehyde (MDA) production. In the cisplatin-treated group the kidney weight as a percent of the total body weight, serum Alb, serum Cr, BUN, GSH content and MDA amount were: 0.61+/-0.054%, 2.84+/-0.24 g dl(-1), 2.99+/-0.10 mg dl(-1), 147.08+/-7.46 mg dl(-1), 3.11+/-0.238 micromol g(-1)and 1449. 09+/-127.36 nmol g(-1), respectively. All the previous changes were significantly (P<0.01) different from the corresponding values in the control group. In addition, histopathological examination of the kidney tissue revealed degenerative cellular material and apoptotic tubular cells were seen in the renal tubules. Rebamipide treatment (140 mg kg(-1), i.p.) for 1 week ameliorated all the previous changes and the results recorded for the cisplatin plus rebamipide-treated group were: 0.45+/-0.035%, 4.17+/-0.091 g dl(-1), 1.37+/-0.209 mg dl(-1), 72.25+/-5.14 mg dl(-1), 5.063+/-0.269 micromol g(-1)and 560.23+/-21.98 nmol g(-1)for the previous tests, respectively. Furthermore, significant improvement in the kidney histopathology was observed. The results of this study clearly revealed that rebamipide protected the kidney against the nephrotoxic effect of cisplatin. These results suggest that lipid peroxidation is not the only mechanism by which cisplatin induced nephrotoxicity. More investigations are needed to confirm the effect of rebamipide and at the same time to elucidate the exact mechanism by which cisplatin induces nephrotoxicity.

Liquid chromatographic assay of nifedipine in human plasma and its application to pharmacokinetic studies.

A highly sensitive, selective and reproducible reversed-phase high-performance liquid chromatographic method has been developed for the determination of nifedipine in human plasma with minimum sample preparation. The method is sensitive to 3 ng/ml in plasma, with acceptable within- and between-day reproducibilities and linearity (r2 > 0.99) over a concentration range from 10-200 ng/ml. Acidified plasma samples were extracted using diethyether containing diazepam as internal standard and chromatographic separation was accomplished on C18 column using a mobile phase consisting of acetonitrile, methanol and water (35:17:48, v/v). The within-day precision ranged from 2.22 to 4.64% and accuracy ranged from 102.4-106.4%. The day-to-day precision ranged from 2.34-7.07% and accuracy from 95.1-100.1%. The relative recoveries of nifedipine from plasma ranged from 91.0-107.3% whereas extraction recoveries were 88.6-93.3%. Following eight 6-week freeze-thaw cycles, nifedipine in plasma samples proved to be stable with accuracy ranging from 0.64 to 3.0% and precision ranging from 3.6 to 4.15%. Nifedipine was also found to be photostable for at least 120 min in plasma, 30 min in blood and for 60 min in aqueous solutions after exposure to light. The method is sensitive and reliable for pharmacokinetic studies and therapeutic drug monitoring of nifedipine in humans after the oral administration of immediate-release capsules and sustained-release tablets to five healthy subjects.

Bioequivalence evaluation of two brands of cefuroxime 500 mg tablets (Cefuzime and Zinnat) in healthy human volunteers.

A bioequivalence study of two oral formulations of 500 mg cefuroxime axetil was carried out in 24 healthy volunteers following a single dose, standard two-treatment cross-over design at the College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, working jointly with King Khalid University Hospital. The two formulations used were Cefuzime (Julphar, United Arab Emirates) as the test and Zinnat (Glaxo Wellcome, England) as the reference product. Both test and reference tablets were administered to each subject after an overnight fasting on two treatment days separated by a 1-week washout period. After dosing, serial blood samples were collected for a period of 8 h. Plasma harvested from blood was analysed for cefuroxime by a sensitive, reproducible and accurate high pressure liquid chromatography (HPLC) method. Various pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max), T(max), T(1/2) and K(el) were determined from plasma concentrations of both formulations and found to be in good agreement with reported values. AUC(0-t), AUC(0-infinity) and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on an analysis of variance (ANOVA); 90% confidence interval for test/reference ratio of these parameters were found within bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Cefuzime is bioequivalent to Zinnat.