Acute temozolomide induced liver injury: mixed type hepatocellular and cholestatic toxicity.

Temozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. His laboratory analysis showed alanine aminotransferase(ALT): 632 IU/L (normal range 0-40); aspartate aminotransferase(AST): 554 IU/L (normal range 5-34); alkaline phosphatase(ALP): 1143 IU/L (normal range 40-150); γ-glutamyl transpeptidase(GGT): 514 IU/L (normal range 9-64 IU/L); total bilirubin: 15.1 mg/dL (normal range 0-1.2); direct bilirubin: 13.2 mg/dL and prothrombin time(PT): 13.5 s, with international normalized ratio (INR): 1.1 (normal range 0.8-1.2). His liver biopsy specimen showed mixed-type (both hepatocellular and cholestatic) hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that TMZ was the probable cause of the acute hepatitis. His liver function tests gradually normalized in 2 months after discontinuation of the drug. In susceptible individuals, TMZ use may lead to acute mixed type liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established. (Acta gastro-enterol. belg., 2016, 79, 363-365).

Acute temozolomide induced liver injury : Mixed type hepatocellular and cholestatic toxicity.

Temozolomide (TMZ) is an oral imidazotetrazine methylating agent which is used for the treatment of glioblastoma multiforme (GBM). We report a case of acute hepatotoxicity in a 53-year old male patient after administration of TMZ for GBM. He had fatigue, nausea, anorexia and jaundice. His laboratory analysis showed alanine aminotransferase(ALT) : 632 IU/L (normal range 0-40) ; aspartate aminotransferase(AST) : 554 IU/L (normal range 5-34) ; alkaline phosphatase(ALP) : 1143 IU/L (normal range 40-150) ; γ-glutamyl transpeptidase(GGT) : 514 IU/L (normal range 9-64 IU/L) ; total bilirubin : 15.1 mg/dL (normal range 0-1.2) ; direct bilirubin : 13.2 mg/dL and prothrombin time(PT) : 13.5 s, with international normalized ratio (INR) : 1.1 (normal range 0.8-1.2). His liver biopsy specimen showed mixed-type (both hepatocellular and cholestatic) hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that TMZ was the probable cause of the acute hepatitis. His liver function tests gradually normalized in 6 months after discontinuation of the drug. In susceptible individuals, TMZ use may lead to acute mixed type liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established. (Acta gastroenterol. belg., 2016, 79, 487-489).

Socioeconomic impact on device-associated infections in limited-resource neonatal intensive care units: findings of the INICC.

PURPOSE: To evaluate the impact of country socioeconomic status and hospital type on device-associated healthcare-associated infections (DA-HAIs) in neonatal intensive care units (NICUs). METHODS: Data were collected on DA-HAIs from September 2003 to February 2010 on 13,251 patients in 30 NICUs in 15 countries. DA-HAIs were defined using criteria formulated by the Centers for Disease Control and Prevention. Country socioeconomic status was defined using World Bank criteria. RESULTS: Central-line-associated bloodstream infection (CLA-BSI) rates in NICU patients were significantly lower in private than academic hospitals (10.8 vs. 14.3 CLA-BSI per 1,000 catheter-days; p < 0.03), but not different in public and academic hospitals (14.6 vs. 14.3 CLA-BSI per 1,000 catheter-days; p = 0.86). NICU patient CLA-BSI rates were significantly higher in low-income countries than in lower-middle-income countries or upper-middle-income countries [37.0 vs. 11.9 (p < 0.02) vs. 17.6 (p < 0.05) CLA-BSIs per 1,000 catheter-days, respectively]. Ventilator-associated-pneumonia (VAP) rates in NICU patients were significantly higher in academic hospitals than in private or public hospitals [13.2 vs. 2.4 (p < 0.001) vs. 4.9 (p < 0.001) VAPs per 1,000 ventilator days, respectively]. Lower-middle-income countries had significantly higher VAP rates than low-income countries (11.8 vs. 3.8 per 1,000 ventilator-days; p < 0.001), but VAP rates were not different in low-income countries and upper-middle-income countries (3.8 vs. 6.7 per 1,000 ventilator-days; p = 0.57). When examined by hospital type, overall crude mortality for NICU patients without DA-HAIs was significantly higher in academic and public hospitals than in private hospitals (5.8 vs. 12.5%; p < 0.001). In contrast, NICU patient mortality among those with DA-HAIs was not different regardless of hospital type or country socioeconomic level. CONCLUSIONS: Hospital type and country socioeconomic level influence DA-HAI rates and overall mortality in developing countries.

Prevalence of hepatitis delta virus (HDV) infection in chronic hepatitis B patients in eastern Turkey: still a serious problem to consider.

Hepatitis delta virus (HDV) is a serious cause of liver-related morbidity and mortality. Coexistent infection with HDV tends to aggravate the course of hepatitis B virus (HBV)-associated liver disease. The aim of this study was to determine the prevalence of HDV infection among patients chronically infected with HBV in the Elazig region, which is in eastern Turkey. A group of 282 patients infected with chronic HBV were investigated for the study. Anti-HDV seropositivity was evaluated in all patients. The anti-HDV-positive patients were further tested for HDV RNA. Severity of liver disease was assessed by liver biopsy. Regression analysis was used to determine the relationship between independent variables and HDV positivity. Of 282 chronic HBV patients, 192 were men (68.1%) and 90 were women (31.9%). The mean age was 43.8 ± 12.7 (between 18 and 73 years). Anti-HDV was positive in 45.5% of the patients (128/282). Among the 128 anti-HDV-positive patients, 116 were checked for HDV RNA and 56.9% were found positive (66/116). Chronic HDV infection rate was therefore present in at least 23.4% of the whole study group (66/282). There were 83 patients with cirrhosis (29.4%) in the study group. Anti-HDV seroprevalence and HDV RNA presence were higher in those with cirrhosis (61.4% and 42.2%, respectively). No significant relationship was found between anti-HDV seropositivity and demographic factors such as age, sex and operation or transfusion history except family history. HDV-RNA-positive patients had significantly higher ALT and lower albumin levels when compared to HDV-RNA-negative patients. HDV-RNA-positive patients also had a significantly higher fibrosis stage. In conclusion, these findings demonstrated that HDV infection is endemic and still a serious problem in the Elazig region of eastern Turkey. HDV infection is significantly related to the family exposure and increases the risk of severe liver fibrosis in this region.

Does early enteral feeding of very low birth weight infants increase the risk of necrotizing enterocolitis?

BACKGROUND/OBJECTIVE: In this retrospective study, we intended to test whether early enteral feeding (EEF) of very low birth weight (VLBW) preterm babies increases the risk of necrotizing enterocolitis (NEC) or not. SUBJECTS AND METHODS: Overall, 297 VLBW preterm babies admitted to the neonatal intensive care unit (NICU) between April 2003 and April 2006 were included. The study consisted of two periods: the first period was between April 2003 and October 2004, when babies were not fed enterally until they were extubated (167 preterm VLBWs). The second period was between November 2004 and April 2006, when babies were fed even when they were intubated, starting preferably on the first day of life (130 preterm VLBWs). Criteria for withholding enteral feeding in both periods were hypotension necessitating vasopressor agent use, abdominal distention, abdominal tenderness and suspected or proven NEC. Possible risk factors for NEC were also recorded. RESULTS: The overall incidence of NEC in VLBW preterm babies was 6.7% and did not differ between the two study periods: 7.2% in the late and 6.2% in the EEF regimens. On logistic regression analysis, the most important risk factors associated with NEC were sepsis (P<0.001) and blood culture positivity (P<0.001). The average daily weight gain was significantly higher in the early fed babies (P=0.011). CONCLUSIONS: The EEF of VLBW preterm babies does not increase the risk of NEC. Increased daily weight gain is an important reason to feed these babies earlier.

Endothelial dysfunction in Turkish patients with non-alcoholic fatty liver disease.

BACKGROUND: The components of the metabolic syndrome are closely related with endothelial dysfunction, which is a pathophysiological issue of cardiovascular diseases. Non-alcoholic fatty liver disease (NAFLD) is considered as one of the components of the metabolic syndrome. The aim of this study was to evaluate the endothelial-dependent dilatation (EDD) and endothelial-independent dilatation (EID) of the brachial artery in NAFLD. METHODS: Fifteen non-alcoholic steatohepatitis (NASH), 17 patients with simple steatosis and 16 healthy subjects formed the study group. Non-alcoholic fatty liver disease group was composed of patients admitted to the gastroenterology outpatient clinic because of increased liver enzymes. Endothelial functions of the brachial artery were evaluated by vascular ultrasound. EDD was assessed by establishing reactive hyperaemia, and EID was determined by using sublingual nitrate. RESULTS: No statistical difference for the basal diameter of brachial artery was found between the groups (P = 0.49). The values for EDD and EID were significantly different across all three groups (P < 0.0001 and P < 0.0001, respectively). EDD and EID were significantly lower in NASH compared with simple steatosis (P = 0.01 and P < 0.01, respectively). However, there was no statistical significance for EDD and EID in simple steatosis groups compared with controls (P = 0.58 and P = 0.98, respectively). CONCLUSIONS: Our study showed that patients with NASH had significantly worse endothelial dysfunction compared with patients with simple steatosis and healthy subjects. The treatment strategies with ameliorative effects for endothelial dysfunction might be effective for delaying the development of cardiovascular complications in NAFLD.

Does birth weight discordance in preterm twins affect neonatal outcome?

OBJECTIVE: To compare neonatal morbidity and mortality between hospitalized discordant and concordant preterm twin pairs. STUDY DESIGN: This was a retrospective, hospital-based study of preterm twins, followed in neonatal intensive care unit. Twins were classified as discordant when the difference in birth weight was >15%. Morbidity and mortality rates were compared between discordant and concordant groups. RESULTS: Of 136 preterm twins in the study, 54 were discordant and 82 were concordant. In discordant twins hypoglycemia and cesarean delivery rate was higher than concordant pairs. The mortality rate did not differ between concordant and discordant groups. CONCLUSIONS: Hospitalized preterm discordant twin pairs have an increased risk of hypoglycemia compared to concordants. Discordant growth is not a risk factor for prolonged hospitalization and increased mortality.

Power Doppler ultrasound mapping in nonobstructive azoospermic patients prior to testicular sperm extraction.

This study was conducted to localize the testicular regions, which have better blood circulation by power Doppler ultrasonography in patients with nonobstructive azoospermia before testicular sperm extraction (TESE), and to investigate whether these vascularized areas have a high sperm retrieval rate or not. We evaluated 110 testes of 55 cases that were diagnosed as nonobstructive azoospermia. The mean age of the study group was 33 years (range 26 to 42). Patients with Y chromosome microdeletions, karyotype and hormonal abnormalities (except elevated FSH levels) were excluded from the study. In all cases, testes were evaluated by power Doppler ultrasonography before testicular sperm extraction. Testis was divided vertically into five equal parts and the area with maximum vascularity was determined subjectively. During testicular sperm extraction, starting from best-perfused areas, biopsies were done. If no motile or sufficient amount of sperm was found, TESE procedure was tried on the contralateral testis. TESE were performed from 82 testes and for the regions that show good and poor vascularity. The sperm finding rate was 38% and 14%, respectively (OR = 3.55)(p = 0.001). Power Doppler ultrasound mapping of the testis in nonobstructive azoospermic cases is a reliable and informative method to assess spermatogenic foci. It is a noninvasive technique that minimizes the unnecessary removal of hormone producing tissue and gives chance to end the TESE earlier than currently practiced procedures.

Efficacy and safety of sildenafil citrate in hemodialysis patients.

Erectile dysfunction (ED) is more frequent among end-stage renal failure patients than the normal population. Sildenafil citrate has been successfully used for the symptomatic treatment of erectile dysfunction. The aim of this study was to determine the efficacy and safety of sildenafil citrate in the treatment of ED in patients on hemodialysis. Fifty-five hemodialysis patients above 18 years suffering from ED with steady sexual partners were included in the study. The first five and fifteenth questions of the International Index of Erectile Function were employed to evaluate ED in the patient group. A Single 50-mg sildenafil citrate tablet was prescribed for each patient. The patients were encouraged to take it on the day after hemodialysis and 1 hour before sexual intercourse. The erectile function of the patients after the treatment was re-evaluated in the same manner by International Index of Erectile Function. The ages of the patients ranged between 30 and 73 years (mean 50.6 +/- 10.9). The overall response rate was 74.5% (38/51). Side effects were nausea (n = 2), palpitation (n = 2), flushing (n = 1), and angina (n = 1). Sildenafil citrate (50 mg) was observed to be safe and effective for treatment of hemodialysis patients with careful evaluation and proper patient selection.

Renal transplantation experience following endoscopic treatment of vesicoureteral reflux.

The most efficacious treatment for end-stage renal disease is renal transplantation. Because high-grade vesicoureteral reflux forecasts potential future complications, the patients studied were subjected to bilateral nephroureterectomy before transplantation. The aim of this study was to investigate the posttransplantation results of a subureteral injection performed before transplantation to treat high-grade vesicoureteral reflux in end-stage renal disease patients. Renal transplantation was performed on 14 of 52 end-stage renal disease patients that had undergone prior subureteral injection. Subureteral injection had been performed in 24 refluxing renal units of these 14 patients. Ten patients had bilateral and 4 patients unilateral reflux. The treatment criterion was reflux of at least grade III; however, when low-grade reflux was present in the contralateral renal unit, it was also treated during the same session. Success was determined as no (complete) or decrease to grade I (partial) reflux. The patient ages ranged between 13 and 46 years (mean 29.3 years). The reflux resolved in 20 of 24 renal units (83%) and was reduced to grade I in 3 of the others (12%), namely resulting in a total response rate of 95%. Except for 1 patient who was lost to follow-up, the other recipients were observed for 6 to 47 months (mean 23 months). Only 1 patient experienced symptomatic urinary tract infection or asymptomatic bacteriuria after renal transplantation. Acute rejection occurred in 5 and chronic rejection in 3 patients. In conclusion, subureteral injection instead of nephroureterectomy seems to be an efficient and minimally invasive alternative for renal transplant recipients with high-grade vesicoureteral reflux.

Covered metallic ureteral stent in the management of malignant ureteral obstruction: preliminary results.

OBJECTIVES: To evaluate the effectiveness of ureteral Dacron-covered metallic stents in the management of malignant ureteral obstruction. METHODS: Covered metallic stents were placed unilaterally using a percutaneous approach in an antegrade fashion into nine ureters of 8 patients with bilateral malignant ureteral obstruction. The contralateral kidneys were drained by percutaneous nephrostomy in 7 patients. The primary diagnoses were rectal cancer in 5 patients and cervical, bladder, and prostate cancers in the remaining cases. RESULTS: Covered metallic stents could be successfully placed in all patients. Only one of nine ureters was stented with a double J-stent. In a mean follow-up of 9 months (range 1 to 14), 7 of 8 patients died because of their primary disease. During the follow-up period, none of the stents were obstructed, displaced, or infected. CONCLUSIONS: Dacron-covered metallic stents appear to be successful in the treatment of patients with malignant ureteral obstruction. The preliminary outcome encourages and justifies the application of this drainage method.

Endoscopic treatment of complete bladder neck obstruction by transurethral Seldinger technique.

Bladder neck contracture is usually a complication of prostatectomy and the treatment of choice in such a condition should be endoscopic surgery. However, in a few patients the bladder neck may be completely obstructed preventing retrograde access into the bladder. A case is presented of complete bladder neck obstruction occurring after transurethral resection of prostate, which was treated after an access was provided by using transurethral Seldinger technique.

Breast milk beta-glucuronidase levels in hyperbilirubinemia.

Breast milk beta-glucuronidase was thought to be one of the etiological factors in the pathogenesis of late-onset breast-milk jaundice, but results of these studies are conflicting. In this study breast milk beta-glucuronidase levels were determined in groups with physiologic jaundice, early breast-feeding jaundice and late breast-milk jaundice. No difference in beta-glucuronidase levels of these three groups was found in samples taken on the 4th and 15th days of life. beta-glucuronidase activity in breast milk declined from the 4th to 15th day in all groups. These results imply that factors other than breast milk beta-glucuronidase activity should be investigated to reveal the pathogenesis of late-onset breast-milk jaundice.

Neurofibroma of the bladder wall in von Recklinghausen's disease.

Neurofibromatosis, or von Recklinghausen's disease, is an autosomal dominant disease with multiple neurofibroma and café-au-lait spots. However, neurofibroma in the bladder wall is a rare condition in von Recklinghausen's disease. A 31-year-old man with neurogenic voiding dysfunction due to sacral meningocele and acute urinary retention with neurofibroma of the bladder wall is presented with detailed radiologic evaluation. Patients with von Recklinghausen's disease should be carefully evaluated if urological symptoms exist.

Anterior urethral valve as a cause of end-stage renal disease.

Although posterior urethral valves are predominant as a cause of obstructive uropathy in children, anterior urethral valves may also appear as the underlying etiologic factor in end-stage renal disease that results from obstruction. Two cases are presented of anterior urethral valve patients that were admitted with end-stage renal disease. The first case was successfully treated with diverticulectomy and urethral reconstruction in preparation for renal transplantation. The second case, however, had been on cystostomy drainage for 6 years and also had a contracted bladder. A more extensive lower urinary tract reconstruction was delayed. Children with poor stream and recurrent infections should be evaluated carefully and anterior urethral valve or diverticula should be considered in differential diagnosis of obstructive lesions.

Combined use of prostate-specific antigen derivatives decreases the number of unnecessary biopsies to detect prostate cancer.

The authors evaluated the prostate cancer detection rate in Turkish patients with prostate-specific antigen (PSA) levels of 4 ng/ml to 10 ng/ml and who had normal digital rectal examination (DRE) findings. They also aimed to evaluate the value of PSA density and percent free PSA in minimizing unnecessary prostate biopsies for these PSA ranges. This prospective study included 134 consecutive men referred for early prostate cancer detection or lower urinary tract symptoms. All men underwent transrectal ultrasound with systematic sextant needle biopsies. The ability of PSA density and percent free PSA to improve the power of PSA in the detection of prostate cancer was evaluated with statistical analyses as well as receiver operating characteristics curves. Among the 134 men, 124 (92.5%) had a benign histology and 10 (7.5%) had cancer diagnosed on the initial biopsies. Despite the disappointing results in regard to the sensitivity and specificity of PSA derivatives alone, the combination of PSA density and percent free PSA significantly increased the area under the curve compared with the use of each test alone. To increase the specificity of PSA in this patient population, the authors recommend combining two PSA derivatives in deciding whether to perform a biopsy. In a PSA range of 4 ng/ml to 10 ng/ml and with normal DRE, a percent free PSA < 21% and a PSA density > 0.18 yields highest specificity with 90% sensitivity.

Serratia marcescens: an emerging microorganism in the neonatal intensive care unit.

As smaller babies survive in neonatal intensive care units, late-onset septicemia with unusual pathogens appears. Between 1 January and 31 December 1998, in Hacettepe University Ihsan Dogramaci Children's Hospital Neonatal Intensive Care Unit, seven infants had S. marcescens isolates. Four babies had septicemia with the microorganism. The case fatality rate was 50 percent in infants with S. marcescens septicemia. The combination of ceftazidime or imipenem with amikacin appears appropriate for the treatment of newborns with Serratia infection.

Clinical experience with BCG alone versus BCG plus epirubicin.

BACKGROUND: Bacillus Calmette-Guérin (BCG) and epirubicin have both been shown to be effective in the treatment of superficial bladder cancer. We studied whether the alternating combination of these agents could improve the efficacy with tolerable side-effects in the treatment of high-risk superficial bladder tumors. METHODS: Forty-one patients with high-risk superficial bladder transitional carcinoma were included in this study. Twenty-one patients were randomized into the BCG group and 20 patients were treated with sequential BCG and epirubicin. The patients were followed for 9-24 months (mean 18 months). Recurrence rates, median time to the first recurrence, progression rate and complications were compared. RESULTS: Fifteen percent of the patients in the BCG and epirubicin group and 19% of the patients in the BCG alone group developed tumor recurrence. Tumor progression was observed in 4.7% and 10% in the BCG/epirubicin group and the BCG alone group, respectively. Median time to first recurrence was 11 months for the BCG/epirubicin group and 16 months for the BCG group (P > 0.05). Three patients in the BCG/epirubicin treatment group developed serious side-effects, which necessitated antituberculosis treatment. CONCLUSION: Because the efficacy of combination was no better than the standard treatment and the alternating combination seemed to be related to a higher incidence of side-effects, this study albeit small, does not recommend combination therapy of BCG and epirubicin in high risk patients with superficial bladder cancer.