The effect of different immunoprophylaxis regimens on post-transplant cytomegalovirus (CMV) infection in CMV-seropositive liver transplant recipients.

BACKGROUND: The effects of different immunoprophylaxis regimens on cytomegalovirus (CMV) infection in liver transplant recipients (LTRs) have not been compared. METHODS: In a cohort, we studied 343 CMV-seropositive recipient (R+) and 83 seronegative donor/recipient (D-/R-) consecutive LTRs from 2004 to 2007. Immunoprophylaxis regimens included steroid-only, steroids plus rabbit anti-thymocyte globulin (rATG), and steroids plus basiliximab. Logistic regression analysis, Cox proportional hazards regression model, and log-rank test were performed for multivariate analysis as appropriate. RESULTS: In total, 164 (39%), 69 (16%), and 193 (45%) patients received steroid-only, basiliximab, and rATG immunoprophylaxis, respectively. CMV infection rates were 15.7% (54/343) in CMV R+ LTRs and 2.4% (2/83) in CMV R- LTRs. Among CMV R+ LTRs who received rATG, the use of at least 6 weeks of CMV prophylaxis reduced the rate of CMV infection from 24.4% (19/78) to 11.7% (9/77). In multivariate analysis, CMV R+ vs D-/R- (odds ratio [OR]=13.1, 95% confidence interval [CI]: 1.8-97.2), rATG >3 mg/kg vs steroid-only induction (OR=1.6, 95% CI: 1.1-2.3), and CMV prophylaxis <6 weeks vs ≥6 weeks (OR=2.7, 95% CI: 1.2-6.4) were independently associated with CMV infection. Subgroup analysis in CMV D-/R+ group who received rATG showed that ≥6 weeks of CMV prophylaxis significantly decreased the risk of CMV infection (OR=1.9, 95% CI: 1.1-3.9; P=.03). CONCLUSION: The use of rATG immunoprophylaxis increases the risk of CMV infection in CMV-seropositive LTRs, specifically in the CMV D-/R+ group. Prophylaxis with valganciclovir in this group for at least 6 weeks decreases the risk of CMV infection.

Hepatitis E virus infection: a general review with a focus on hemodialysis and kidney transplant patients.

BACKGROUND: Hepatitis E virus (HEV) infection is a self-limited viral disease that causes acute hepatitis epidemics in developing countries. The common route of transmission for HEV is supposedly fecal-oral. Serological evidence may be unexpectedly found in hemodialysis (HD) patients and kidney transplant recipients. Although the route of HEV transmission is not usually determined in HD subjects, this virus seems to be transmitted either directly through HD or nosocomially. In this study, we gathered the published information on HEV infection in HD patients and kidney transplant recipients. METHODS: For this review, we collected the relevant articles by searching through Medline and Google Scholar from January 1980 up to September 2009. RESULTS: Some variables including older age, low education, living in rural versus urban areas and the duration of HD seem to be risk factors for HEV infection in HD patients. Compared with non-HD subjects, HEV infection may be specifically associated with poor outcome in HD patients. Specific considerations seem to be required to prevent transmission of HEV to HD patients. CONCLUSION: More extensive investigations are required to determine the disease burden of HEV infection in HD subjects in countries which experience outbreaks of HEV infection.

Is {beta}-interferon a promising therapeutic option for the management of hepatitis C?

Using interferon-alpha (IFN-alpha) as the conventional therapeutic antiviral drug, physicians generally achieve a treatment success of <50% in cases with chronic hepatitis C. Owing to the structural similarities between IFN-alpha and interferon-beta (IFN-beta), the latter is a candidate for obtaining sustained viral response. In this review, we have compiled the published information on the use of IFN-beta for the management of acute and chronic hepatitis C up to 2007. We have looked at the rates of success and side effects. IFN-beta might be helpful if IFN-alpha fails to achieve a favourable outcome. This antiviral drug may be helpful for the management of chronic hepatitis C in both age extremes, in case of a relapse after receiving IFN-alpha and for preventing the development of the carrier state after acute hepatitis C. Further studies are required on the efficacy of IFN-beta for the management of acute and chronic hepatitis C.

Therapeutic aspects of hepatitis C in hemodialysis patients.

BACKGROUND: Since hemodialysis (HD) patients usually suffer from multiple clinical problems and drug side effects, the treatment of hepatitis C in these patients still remains a challenging problem. METHODS: We identified eligible studies using a wide-spectrum search up to May 2007 in MEDLINE (since 1966) and EMBASE (since 1980). Two researchers (S.M.H.M. and M.R.) independently reviewed the manuscripts identified by the search strategy. To determine the most current information, only studies that had been published after 1995 were included. RESULTS: Interferon (IFN)-alpha has long been used for this purpose; however, more recently the advent of pegylated (PEG) IFN has proven to be more beneficial in these patients. Even though the usage of ribavirin is promising in the case of hepatitis C in otherwise healthy subjects, the utilization of this drug in patients with renal failure may be accompanied by catastrophic complications. CONCLUSION: Although both conventional IFN and PEG-IFN seem to be favorable options for the management of hepatitis C in HD patients, further studies on new therapeutic agents are required.

Hepatitis C in hemodialysis patients: current global magnitude, natural history, diagnostic difficulties, and preventive measures.

Hepatitis C virus (HCV) infection is a significant cause of morbidity and mortality in hemodialysis (HD) patients. The reported prevalence of HCV among the HD population has varied greatly from 1.9 to 84.6% in different countries in recent years. The length of time on HD is generally believed to be associated with HCV acquisition in HD subjects. Nevertheless, several recent reports failed to recognize any significant role of blood transfusion. Although there are some considerations about the accuracy of serologic testing in detecting HCV in HD patients, the accumulated data in this review suggest the false-negativity rate to be not more than 1.66% (153/9,220). Therefore, substituting virologic for serologic testing in the routine diagnosis of HCV infection in HD patients seems unreasonable. Several phylogenetic analyzes of viral isolates suggested nosocomial patient-to-patient transmission of HCV among HD patients for which the main potential source is believed to be contaminated hands and articles. However, isolation of HCV-infected HD patients and use of dedicated machines are currently unjustified while strict adherence to universal precautions seems to be enough to control disease spread in HD units. The present article is an update on epidemiological and clinical features of HCV in HD population.

Reconstruction of bladder and urethra using ileocecal segment and appendix in patients with exstrophy-epispadias complex: the first report of a new surgical approach.

OBJECTIVE: We aimed to describe our experience in administering an innovative surgical technique to treat pediatric cases of exstrophy-epispadias complex. MATERIAL AND METHODS: Between 1995 and 2004, seven consecutive patients (six males) with exstrophy-epispadias complex were treated using ileocecal segment for bladder augmentation and appendix for urethral reconstruction. In a single-stage operation, the exstrophied bladder was dissected- and a segment of cecum, ascending colon, terminal ileum, and the corresponding appendix were isolated. Using the opened colon to augment the bladder, the ileal segment was fashioned to skin as temporary stoma, and the appendix was laid in the urethral lumen as the neourethra following urethral demucosation. This technique was used as a secondary surgery in one case and as a primary surgery in six neonates. Evaluation of the urinary tract status was performed by cystograms and ultrasonograms. RESULTS: Renal function was saved in all cases and continence was achieved by clean intermittent catheterization every two hours either via the neourethra (n = 6) or through the temporary stoma (n = 1). The patients did not experience any metabolic complications in their follow-ups. Moreover, no one had vesicourethral reflux, dehiscence, or fistula. CONCLUSIONS: The technique was deemed safe with acceptable outcomes even when secondary repair of previously failed operation was intended. Experiencing the technique in larger cohorts as well as longer follow-ups might be necessary to assess probable long-term complications.

Prevalence of hepatitis B, hepatitis C, human immunodeficiency virus, and syphilis among street children residing in southern Tehran, Iran.

Street children are among vulnerable people in the world. They are one of the main groups in the society who affect the pattern of health. To determine the prevalence of hepatitis B, hepatitis C, human immunodeficiency viruses (HIV), and syphilis among street children residing in southern Tehran, Iran. In a cross-sectional study, we selected 102 children aged below 15 years from southern Tehran. The selected children had an interview and were examined. From each child a blood sample was taken and tested for anti-HIV (ELISA), anti-HCV (ELISA), HBsAg (ELISA), anti-HBs, anti-HBc (radioimmunoassay [RIA]), rapid plasma reagin (RPR), and fluorescent treponema antibody absorption (FTA-ABS). We studied 39 (38%) boys and 63 (62%) girls, including 79 (77%) Afghan and 16 (16%) Iranian children. The nationality of 8 children could not be identified. The children were negative for syphilis, HIV, and HCV. Nevertheless, 3 of them were positive for HBsAg and 15 were HBsAb positive (>10 MIU/mL). The majority of street children are immigrants. Although these children did not have syphilis, HIV, and HCV, they are at risk of HBV.

The frequency of HHV-8 infection in otherwise healthy blood donors as well as renal allograft recipients living in Iran.

BACKGROUND: Different reports from Middle East countries demonstrated Kaposi's sarcoma (KS) in transplant population. This vascular malignancy occurs mostly among immunocompromised individuals. Human herpesvirus 8 (HHV-8) appears to be the causative factor for the development of this neoplasm. Transplant programs are concerned about the frequencies of HHV-8 infection either in general population or transplant patients. METHODS: The current study was conducted in two phases. Firstly, we detected antibodies against HHV-8 in 790 otherwise healthy blood donors. Secondly, a total of 125 kidney allograft recipients evaluated as being seropositive for HHV-8. We utilized enzyme immunoassay (EIA) for serologic studies. RESULTS: Among blood donors, the male to female ratio was 1.05 (405 vs. 385 ) while the mean age was 38.9 ± 11.7 years. The serostatus of none of these blood donors were positive for HHV-8. Among kidney recipients, the male to female ratio was 1.9 (82 vs. 43). The mean age was 39.01 ± 14.77 years. Two (1.6%) patients were seropositive for HHV-8. CONCLUSION: The prevalence of HHV-8 infection among Iranians is likely to be low. Yet, owing to the evidence of this infection among kidney allograft recipients and its probable role in developing post- transplantation KS (PT-KS), further studies appear to be required to keep the various aspects of this infection under close surveillance.

Association between the evidence of human papilloma virus infection in bladder transitional cell carcinoma in men and cervical dysplasia in their spouses.

BACKGROUND: Cervical cancer is one of the most common tumors in women. One of its risk factors is direct contact with viruses, in particular human papillomavirus (HPV). Recent studies have shown a prevalence of 2%-35% for HPV in cases with bladder cancer. In addition, some malignancies of the urogenital organs in males may promote the probability of cervical cancer in their spouses.  In this study, the relationship between cervical dysplasia in women and evidence of HPV infection in tissue specimens obtained from their spouses' bladders has been investigated. METHODS: This cross-sectional study was conducted on 82 male patients with bladder tumors and their spouses between February 2004 and February 2007 in Tehran. We gathered data related to the histopathology of the transitional cell carcinoma (TCC) in men and Pap smear tests of their spouses. Tissue specimens of patients with bladder TCC were analyzed for HPV infection using polymerase chain reaction (PCR). HPV-positive specimens were tested for subtypes 16 and 18. RESULTS: In 24 (29.3%) men, bladder tumor samples were positive for HPV infection. Of these, we found HPV-18 infection in 9 (37.5%), while 3 (12.5%) were infected with HPV-16. In the spouses of those men with HPV-infected bladder tumors, 4 (4.9%) cases had cellular dysplasia noted on their Pap smear tests. We found no dysplasia in those women whose husbands had bladder TCC, but no HPV infection (P = 0.006). CONCLUSION: It is possible to decrease the incidence of bladder TCC in men and cervical cancer in women through public education regarding the methods of transmission and avoidance of risky sexual behaviors.

Efficacy of HBV vaccination in various stages of chronic kidney disease: is earlier better?

BACKGROUND: Despite improvement in hepatitis B infection prevention through national vaccination programs, implementation of compulsory and thorough blood donor screening, and reduction of transfusion numbers due to erythropoietin administration,hepatitis B remains a major concern in hemodialysis (HD) centers [1]. Compared to aresponse rate of over 90% in the normal population, only 50 to 60% of those with endstage renal disease (ESRD) achieve protective antibody levels following immunization against hepatitis B [2][3]. Various strategies have been developed to overcome the low seroconversion rate in ESRD patients, including co-administering zinc, gamma-interferon,thymopentin, interleukin-2, and levamisole as immunostimulants or adjuvants [3][4],changing the injection mode (intradermal versus intramuscular), or doubling the vaccine dose [5]. OBJECTIVES: Previous studies demonstrated that renal failure patients benefit from HBV vaccination; however, not all studies have demonstrated this. Therefore, we compared the rates of seroconversion (hepatitis B surface antibody [HBsAb] titer > 10 IU/mL) in patients at various stages of chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) who received HBV vaccination. PATIENTS AND METHODS: A total of 167 patients in 3 different stages of CKD were vaccinated against HBV. Each patient received the vaccine according to a standardized vaccination schedule consisting of 40 µg of the recombinant vaccine "Engerix" at 0, 1, and 6 months.Eight to 12 weeks after the last dose of vaccination, anti-HBsAb levels were measured. RESULTS: Mean age and eGFR were 57.4 ± 16.5 years and 26.7 ± 14.7 mL/min/1.73 m2, respectively.The overall seroconversion rate was 78%. Although a significant correlation between HBsAb titer and eGFR (r = 0.265, P = 0.001) was observed, in the multivariate analysis using age, CKD stage, diabetes mellitus, and gender as independent variables,the degree of renal function did not significantly contribute to seroconversion. In contrast,higher age (> 60 years) showed a significant negative correlation to seroconversion (odds ratio = 0.22; P = 0.004). CONCLOUSIONS: CKD patients of advanced age should be vaccinated against HBV. Although higher eGFR was not associated with improved seroconversion, the persistence of seroconversion was not evaluated; future studies should be conducted to develop recommendations for earlier or later vaccination.

Prevalence of HBV, HCV, HIV and syphilis among homeless subjects older than fifteen years in Tehran.

Homeless people are usually prone to be infected with multiple infectious diseases such as human immunodeficiency virus, hepatitis B virus, and hepatitis C virus, as well as syphilis. In this cross-sectional study, using a questionnaire and enzyme-linked immunosorbant assay, we evaluated the seroprevalance of hepatitis B and C viruses, human immunodeficiency virus, and syphilis, as well as their risk factors in 202 homeless men. A total of 70 (34.7%), 87 (42.8%), and 13 (6.4%) subjects were infected with hepatitis B, hepatitis C and human immunodeficiency viruses, respectively. Ten (0.5%) had a simultaneous infection with hepatitis B and C viruses and human immunodeficiency virus. Only one participant was seropositive for rapid plasma reagin. History of smoking and opium addiction was present in 144 (71.6%) and 109 (54.2%) subjects, respectively. Although all human immunodeficiency virus-positive subjects were hepatitis C virus positive, 10 (76.9%) had a history of intravenous drug abuse. Risk factors including intravenous drug abuse (P<0.005) and imprisonment (P<0.05) were significantly associated with all the three infections. We found no significant association between high-risk sexual behavior and these infections. Although syphilis seems not to be an important risk factor among homeless adults, all hepatitis B, hepatitis C, and human immunodeficiency virus infections have quite noticeable frequencies among Iranian subjects. History of intravenous drug abuse should be taken into account in screening of homeless people.

An estimation of the chronic rejection of kidney transplant using an eternal Weibull regression: a historical cohort study.

BACKGROUND: We estimated the chronic rejection of kidney transplant using an eternal Weibull regression. METHODS: In this historical cohort study, we enrolled all patients with chronic renal failure who were admitted to Shahid Labbafinejad medical center (Tehran, Iran) from 1984 to 2003. Using Matlab 7.0, we considered the eternal proportion theta, as a logistic-type function of the covariates and modified the survival function. We estimated the survival function in unmodified and modified forms using Weibull distribution. RESULTS: The chance of chronic rejection was 1.95 times higher among those who received a kidney transplant before 1996. Considering all cases who received renal transplantation after 1984, males had a chance of rejection 20% less than females. Next to the eternity, Weibull model was fitted to patients who received renal transplantation after 1996. Treatment protocol was changed after 1996 expecting fewer chronic rejections; thereafter, the eternal proportion was estimated to be 0.81. This seems quite considerable as a percentage of non-failure cases. CONCLUSION: Providing a non-zero eternal proportion, the modified model would be superior over the unmodified model.

Special characteristics of culturing mature human bladder smooth muscle cells on human amniotic membrane as a suitable matrix.

INTRODUCTION: Our aim was to evaluate the natural behavior, growth pattern, morphology, and specific features of human bladder smooth muscle cells (HBSMCs) on two different matrixes, including human amniotic membrane (HAM) and collagen. MATERIALS AND METHODS: The HBSMCs were obtained from 6 children with primary vesicoureteral reflux undergoing open antireflux surgery, and they were isolated from the anterior wall of the bladder. The specimens were cultured on a tissue culture plate of bovine dermal collagen serving as control and on decellularized HAM. Histological, transmission electron microscopy, and immunocytochemical examinations were done, thereafter. RESULTS: On HAM, very few HBSMCs slowly migrated from explant tissue on the 7th day of culture. All the cells were placed at the same direction, and in some parts, formed multilayer. After 35 to 40 days, the confluency rate was 75% and the cells were orderly arranged. On collagen, cell migration from explant culture took place as rapidly as the 3rd to 4th day of culturing. On days 30 to 40, the confluency rate was 100%. Immunocytochemical staining was positive for anti-actin and antidesmin antibodies. On transmission electron microscopy, cell organelles of HBSMCs exhibited the same features of the natural smooth muscle cells. They were tightly attached to each other and the underlying layer basement membrane. CONCLUSION: A well-designed growth pattern of HBSMCs on HAM with abundant cell-to-cell adhesions encourages us to use it as a competent tissue for reconstruction of relatively damaged or diseased bladders. Undoubtedly, further clinical studies should be performed to replicate our results.

Ureteral calculi in children: what is best as a minimally invasive modality?

INTRODUCTION: Minimally invasive treatment of ureteral calculi in children is a challenging topic. In an evidence-based review, we evaluated the efficacy and safety of extracorporeal shock wave lithotripsy (SWL) and ureteroscopic modalities for this group of patients. MATERIALS AND METHODS: In this study, we performed a comprehensive systematic review on articles appeared in the PubMed from 1998 to March 2008. We selected all papers addressing SWL or ureteroscopic management of the ureteral calculi in children and determined the level of evidence of the presenting data. RESULTS: Thirty-nine articles were reviewed and 24 with valid information on SWL or ureteroscopic management of the pediatric ureteral calculi were analyzed. Six articles (25%) were randomized controlled trials and 18 (75%) were retrospective case-controls or case series. The following data were extracted from the 24 articles: in SWL groups, overall success rate was 84.1% (range, 71% to 100%) for the upper ureteral calculi and 76.2% (range, 19% to 91%) for the lower ureteral calculi. Only 61% of the patients had only 1 treatment course, while 8% and 31% of the cases required 2 and more than 2 sessions of treatment, respectively. With ureteroscopic management, the overall success rates were 93.2% (range, 81% to 100%) and 74.4% (range, 20% to 100%) in the lower and upper ureteral calculi, respectively. CONCLUSION: The main limitations of the series on minimally invasive treatment of pediatric ureteral calculi are lack of powerful randomized controlled trials or prospective data and insufficient patient numbers. Therefore, it is difficult to draw absolute conclusions about successful treatment based on current knowledge.

Role of laparoscopic nephrectomy for management of symptomatic nephrogenic hypertension.

OBJECTIVES: To investigate the efficacy of laparoscopic nephrectomy for the management of hypertension associated with a unilateral poorly functioning kidney in adults and the role of some variables in the prediction of its outcome in the management of nephrogenic hypertension. METHODS: We conducted this study on 22 hypertensive patients with a unilateral, minimally functioning kidney. We included patients with a well-functioned contralateral kidney, no renal tumors, no renovascular hypertension, and no diagnosis of end-stage renal disease. All patients had poorly controlled hypertension or preferred to discontinue medical therapy. Their age at the onset of hypertension, gender, age at laparoscopic nephrectomy, and the interval from diagnosis to intervention were evaluated. A complete response was defined as blood pressure normalization without medical treatment. A partial response was defined as a decrease in the medication requirements and/or a 10-mm Hg decrease in diastolic blood pressure after surgery. Measurement of plasma renin activity was not available in our country at the time of the study. RESULTS: After nephrectomy, 12 (54.5%), 2 (9.1%), and 8 (36.4%) patients had a complete, partial, or no response to the surgery, respectively. No significant association was found between the response to laparoscopic nephrectomy and age, gender, and mean blood pressure. Only the hypertension-related signs and symptoms before surgery were significantly associated with the response to laparoscopic nephrectomy (P = 0.01) on both univariate and multivariate analysis. CONCLUSIONS: Nephrectomy seems effective for the management of nephrogenic hypertension in patients who wish to discontinue medical therapy. We suggest paying attention to the preoperative hypertension-related symptoms for the prediction of the response to nephrectomy.

Diagnosis of bladder cancer by urine survivin, an inhibitor of apoptosis: a preliminary report.

INTRODUCTION: Survivin is an inhibitor of apoptosis that is expressed in undifferentiated tissues like tumors. Detection of survivin in urine has been proposed as a diagnostic marker for bladder cancer. We evaluated the urine samples of patients with bladder cancer for survivin and compared them with healthy controls. MATERIALS AND METHODS: The urine specimens of 20 patients with transitional cell carcinoma (TCC) of the bladder (group 1) and 18 controls without cancer (group 2) were collected before cystoscopy and assessed for survivin by reverse transcriptase polymerase chain reaction. RESULTS: All patients except 1 in group 1 were men. Urine specimens were positive for survivin in 18 (90%) and 9 (50%) patients of groups 1 and 2, respectively (P = .007). Sixteen patients with TCC had urine cytology, of which 6 (37.5%) were positive. Urine survivin was positive in all 10 patients with negative cytology. Nine patients in this group had low-grade tumors. CONCLUSION: Urine survivin seems to have a higher sensitivity than urine cytology, especially in low-grade bladder cancer. The quantitative measurement of survivin in urine by advanced techniques may provide a better diagnostic and prognostic tool. However, the clinical use of survivin and its association with different stages and grades of TCC still requires more studies.

Distribution of hepatitis C virus genotypes among hemodialysis patients in Tehran--a multicenter study.

Hepatitis C virus has substantial heterogeneity of genotypes throughout the world. The aim of this study was to determine the frequency of HCV genotypes, risk factors and clinical implications in cases of hemodialysis living in Tehran. A total of 155 patients treated by hemodialysis, who had been identified to be anti-HCV positive at 45 medical centers in Tehran, were enrolled. Genotyping was using restriction fragment length polymorphism (RFLP) on HCV-RNA positive samples. HCV-RNA was detected in 66 (42.6%) patients. Genotyping of HCV-RNA positive serum samples demonstrated that subtypes 3a and 1a were predominant accounting for 30.3 and 28.8%, respectively. The distribution of other HCV genotypes showed genotype 1b, 18.2%; genotype 4, 16.7%; mixed genotypes 1a and 1b, 3%; and genotype 3b, 3%. Genotype 2 was not detected in this study. Statistically significant differences were identified between HCV infected and non-HCV infected patients regarding history of hemodialysis unit changes more than two times (P = 0.01), and history of hemodialysis for more than 20 years (P = 0.02). However, blood transfusion, mean duration of hemodialysis therapy and the history of solid organ transplantation did not differ between these two groups. This study indicates that the dominant HCV genotypes among patients treated by hemodialysis living in Tehran were 3a and 1a, and considering previous reports from the general population, genotype 4 was strongly associated with hemodialysis. The duration of treatment by hemodialysis and, in turn, more hemodialysis unit changes will lead to more frequent HCV infections.