PubMed Health⌕ Search

Biomedical subjects

Robert S Brown

Publications and source records attributed to Robert S Brown.

At least 19 recordsLinked to original sources
PubMed2007

Outcomes in hepatitis C virus-infected recipients of living donor vs. deceased donor liver transplantation.

In this retrospective study of hepatitis C virus (HCV)-infected transplant recipients in the 9-center Adult to Adult Living Donor Liver Transplantation Cohort Study, graft and patient survival and the development of advanced fibrosis were compared among 181 living donor liver transplant (LDLT) recipients and 94 deceased donor liver transplant (DDLT) recipients. Overall 3-year graft and patient survival were 68% and 74% in LDLT, and 80% and 82% in DDLT, respectively. Graft survival, but not patient survival, was significantly lower for LDLT compared to DDLT (P = 0.04 and P = 0.20, respectively). Further analyses demonstrated lower graft and patient survival among the first 20 LDLT cases at each center (LDLT 20; P = 0.002 and P = 0.002, respectively) and DDLT recipients (P < 0.001 and P = 0.008, respectively). Graft and patient survival in LDLT >20 and DDLT were not significantly different (P = 0.66 and P = 0.74, respectively). Overall, 3-year graft survival for DDLT, LDLT >20, and LDLT 20 were not significantly different. Important predictors of graft loss in HCV-infected patients were limited LDLT experience, pretransplant HCC, and higher MELD at transplantation.

Adult↗
PubMed2007

Hepatitis C-associated granulomas after liver transplantation: morphologic spectrum and clinical implications.

Liver granulomas have been described in biopsy specimens from people with de novo chronic hepatitis C virus (HCV) infection and in allograft biopsy specimens from recipients of transplants for HCV-related liver disease. The latter have not been well studied, and there are no data regarding the prevalence, morphologic spectrum, and clinical significance of HCV-associated granulomas after liver transplantation. We observed granulomas in allograft liver biopsy specimens of 4 (8%) of 53 recipients of transplants for HCV-related end-stage liver disease during a 3-year period. Initial appearance of granulomas ranged from 4 to 41 weeks after transplantation. Lobular and portal nonnecrotizing, epithelioid granulomas and lobular microgranulomas were observed, with the latter predominating. Serum transaminase and alkaline phosphatase levels were significantly higher in patients with granulomas than in age- and sex-matched control subjects, but histologic disease activity, cellular rejection scores, HCV genotypes, viral titers, and retransplantation rate owing to recurrent disease were not significantly different. Our study suggests that a granulomatous response to HCV infection occurs in a subset of patients after transplantation; however, this histologic finding does not portend a worse clinical outcome.

Adult↗
PubMed2006

Protective antibody levels and dose requirements for IV 5% Nabi Hepatitis B immune globulin combined with lamivudine in liver transplantation for hepatitis B-induced end stage liver disease.

Lamivudine combined with Hepatitis B immune globulin (HBIg) prevents post liver transplant (LT) HBV recurrence. The study was designed to assess the impact of lamivudine on hepatitis B antibody (anti-HBs) and dosage requirements of intravenous 5% HBIg (Nabi-HB) in the first 36 weeks post LT. Adults undergoing LT for chronic HBV received lamivudine prior to or at LT, and IV HBIg 20,000 IU on day of LT, 10,000 on days 1-7, weeks 4 and 8, and 5,000 every 4 weeks thereafter. Replicative status based on serum HBV DNA (> 5 pg/mL = replicator (R) or < or = 5 pg/mL = nonreplicator (N) was determined at initiation of lamivudine (R or N) and within 2 weeks of LT (r or n), resulting in 3 groups: Nn, Rn, and Rr. Between December 1999 and May 2001, 30 patients (10 Nn, 13 Rn, 6 Rr, and 1 unknown), mean age of 52 years underwent LT. HBsAg neutralization was achieved with anti-HBs > 300 IU/L during week 1 and > 200 IU/L during weeks 2-12. All but one patient were HBsAg-negative on last follow-up. Pre-LT suppression of HBV replication resulted in similar dose requirements and pK in the Rn and Nn groups within 1 week after LT. Comparatively, the Rr group had greater HBIg requirements during weeks 1-12 due to greater anti-HBs clearance and shortened t(1/2) during the entire 36-week follow-up. In conclusion, this study provides a rationale for the use of lower HBIg doses in HBV patients with suppressed replication undergoing LT.

Adult↗
PubMed2006

Hepatitis C virus and liver transplantation.

Hepatitis C virus (HCV) infection remains the most common cause of hepatic failure requiring orthotopic liver transplantation, and the disparity between the number of patients in need of liver replacement and the number of organs available continues to grow. Unfortunately, without viral eradication before transplantation, HCV recurrence is universal and is associated with poor graft and patient survival. Despite expansion of the donor pool and attempts to suppress HCV activity with various pretransplant and posttransplant antiviral therapies, many questions remain. This article reviews the literature regarding the evaluation of patients for transplantation, the antiviral therapies available in the peritransplant period, the immunosuppressive regimens, used, and the approach to patients with recurrent HCV infection.

Graft Survival↗
PubMed2006

Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1.

BACKGROUND & AIMS: Compared with Caucasian Americans (CA), African Americans (AA) with chronic hepatitis C are less likely to respond to interferon-based antiviral therapy. METHODS: In a multicenter treatment trial, 196 AA and 205 CA treatment-naive patients with hepatitis C virus (HCV) genotype 1 infection were treated with peginterferon alfa-2a (180 microg/wk) and ribavirin (1000-1200 mg/day) for up to 48 weeks. The primary end point was sustained virologic response (SVR). RESULTS: Baseline features were similar among AA and CA, including HCV-RNA levels and histologic severity, but AA had higher body weights, a higher prevalence of diabetes and hypertension, and lower alanine transaminase levels (P < .001 for all). The SVR rate was 28% in AA and 52% in CA (P < .0001). Racial differences in viral responses were evident as early as treatment week 4. Breakthrough viremia was more frequent among AA than CA (13% vs 6%, P = .05); relapse rates were comparable (32% vs 25%, P = .30). Proportions of patients with serious adverse events and dose modifications and discontinuations were similar among AA and CA. In multiple regression analyses, CA had a higher SVR rate than AA (relative risk, 1.96; 95% confidence interval, 1.48-2.60; P < .0001). Other factors independently associated with higher SVR included female sex, lower baseline HCV-RNA level, less hepatic fibrosis, and more peginterferon taken. CONCLUSIONS: AA with chronic hepatitis C genotype 1 have lower rates of virologic response to peginterferon and ribavirin than CA. These differences are not explained by disease characteristics, baseline viral levels, or amount of medication taken.

Adolescent↗
PubMed2006

Ground-glass, polyglucosan-like hepatocellular inclusions: A "new" diagnostic entity.

BACKGROUND & AIMS: Ground-glass (GG) inclusions within hepatocytes are an important histopathologic marker of chronic hepatitis B virus (HBV) infection but may also be seen in Lafora's disease (myoclonus epilepsy), cyanamide alcohol aversion therapy, and type IV glycogenosis. We have noted a recent increased incidence of liver biopsy and postmortem specimens with GG inclusions associated with none of these etiologic factors. This study was undertaken to further delineate the clinical and liver pathologic features in such cases and their possible pathogenesis. METHODS: Ten cases with GG inclusions (8 biopsy, 2 postmortem) were examined by light and electron microscopy, and the patients' clinical records were reviewed. RESULTS: Light microscopy demonstrated pale pink, oval to crescentic intracytoplasmic inclusions with a predilection for periportal hepatocytes but sometimes present throughout the lobules. The inclusions were intensely positive on periodic acid-Schiff stain and digested with diastase. Transmission electron microscopy of two cases showed non-membrane-bound cytoplasmic collections of granules with mild-to-moderate electron density, consistent with abnormal glycogen granules. The patients included 7 transplant recipients (liver, hematopoietic stem cell), 3 with type 2 diabetes and a child on chronic parenteral nutrition for short bowel syndrome. Medications included immunosuppressive agents, antibiotics, and insulin. CONCLUSIONS: GG hepatocellular inclusions may be seen in individuals without HBV infection or other recognized etiologies, appear to be composed of abnormal glycogen and closely resemble polyglucosan bodies described in humans, animals, and experimental models. The possible pathogenetic roles of disturbed glycogen metabolism and polypharmacotherapy are stressed.

Adolescent↗
PubMed2005

Hepatitis C and liver transplantation.

Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

Hepatitis C↗
PubMed2005

Peginterferon alpha-2a combination therapies in chronic hepatitis C patients who relapsed after or had a viral breakthrough on therapy with standard interferon alpha-2b plus ribavirin: a pilot study of efficacy and safety.

There are no established therapeutic regimens for hepatitis C virus (HCV) patients who relapse following treatment with interferon alpha-2b and ribavirin or those who break through while on interferon alpha-2b and ribavirin. We therefore evaluated various combination therapies in HCV patients who relapsed or experienced a viral breakthrough. Patients (n = 124) were randomized to 48 weeks of treatment with once-weekly subcutaneous injections of 180 microg pegylated (peg-) interferon alpha-2a plus oral ribavirin (800-1000 mg/day), mycophenolate mofetil (2 g/day), amantadine (200 mg/day), or ribavirin and amantadine and followed for an additional 24 weeks. The sustained virologic response was higher in patients administered peginterferon alpha-2a plus ribavirin (38%) or ribavirin and amantadine (45%) than in those administered peginterferon alpha-2a plus mycophenolate mofetil (17%) or amantadine (10%). As in previous studies, patients with genotype non-1 and those with lower viral loads had better responses than those with genotype 1 and high viral loads, though the differences did not reach significance. The four treatment regimens had similar safety profiles, except that patients receiving ribavirin had greater maximal hemoglobin decreases. These findings suggest that the combination of peginterferon alpha-2a plus ribavirin or with ribavirin and amantadine is effective in some HCV patients who relapse after treatment with interferon alpha-2b plus ribavirin.

Alanine Transaminase↗
PubMed2005

A randomized trial of pegylated interferon alpha-2b plus ribavirin in the retreatment of chronic hepatitis C.

OBJECTIVES: The efficacy of combination therapy with pegylated interferon (PEG IFN) alpha plus ribavirin (RBV) in the retreatment of chronic hepatitis C (CHC) in patients who previously failed combination standard IFN plus RBV or IFN monotherapy has not been well established. METHODS: Three hundred and twenty-one CHC patients including virologic nonresponders to combination IFN plus RBV (n = 219) or IFN monotherapy (n = 47), and relapsers to combination therapy (n = 55) were randomized to receive PEG IFN alpha-2b 1.5 microg/kg per wk plus RBV 800 mg per day (Regimen A, n = 160) or PEG IFN alpha-2b 1.0 microg/kg per wk plus RBV 1,000-1,200 mg per day (Regimen B, n = 161) for 48 wks. RESULTS: Sustained virologic response (SVR) occurred in 16% of the overall study population (Regimen A vs B, 18%vs 13%, p= 0.21), in 8% of the combination therapy nonresponders (10%vs 6%, p= 0.35), in 21% of the IFN monotherapy nonresponders (16%vs 27%, p= 0.35), and in 42% of the combination therapy relapsers (50%vs 32%, p= 0.18). In nonresponders to prior combination therapy, HCV ribonucleic acid levels <100,000 copies/mL at the end of the prior treatment course were associated with an increased SVR compared with levels >or=100,000 copies/mL (21%vs 5%, p= 0.002). In the overall study population, genotype 1 patients had lower SVR rates than others (14%vs 33%, p= 0.01), and African Americans had lower SVR than Caucasians (4%vs 18%, p= 0.01). CONCLUSION: Combination therapy with PEG IFN alpha-2b plus RBV is more effective in patients who relapsed after combination standard IFN plus RBV than in nonresponders to either combination therapy or IFN monotherapy. There was no significant effect of dosing regimen.

Black or African American↗
PubMed2005

The spectrum of chronic hepatitis C virus infection in the Virginia Correctional System: development of a strategy for the evaluation and treatment of inmates with HCV.

BACKGROUND AND OBJECTIVE: Chronic hepatitis C virus (HCV) is common in the inmate population of the United States. Long-standing HCV can progress to cirrhosis, which can contribute to significant morbidity and mortality. However, those inmates with histologically mild disease are unlikely to develop liver-related morbidity or mortality during their period of incarceration. Our objective was to develop an economic strategy for evaluation and treatment of inmates with chronic HCV. METHODS AND MEASURES: A retrospective cohort analysis of 302 inmates within the Virginia Department of Corrections (VDOC) who underwent liver biopsy for chronic HCV at the Virginia Commonwealth University Health System between 1998 and 2002 was performed. The data from this analysis was to utilized to develop a cost model for treatment of chronic HCV in this population based upon biochemical or histologic criteria. We used the perspective of the VDOC using actual costs paid to providers, hospitals, and pharmacies. The primary endpoint was cost-effectiveness of HCV treatment. RESULTS: Eighty percent of inmates with chronic HCV were genotype 1, 49% had a normal value for serum ALT at the time of evaluation, 30% had no fibrosis, and 24% had bridging fibrosis or cirrhosis. The cost to evaluate and treat 100 consecutive inmates with peginterferon and ribavirin regardless of serum ALT and liver histology was calculated to be $1,775,900 or $35,500 per sustained virologic response (SVR). Although the cost declined by 50% if only those patients with an elevated serum ALT were treated, 45% of those inmates with varying degrees of fibrosis, and 21% with cirrhosis would not have received therapy utilizing this scenario. In contrast, the cost of performing liver biopsy and treating only those patients with any degree of fibrosis was $1,367,043; a savings of slightly more than $400,000 per 100 patients evaluated. The overall cost of treatment was most influenced by the price of peginterferon and ribavirin, which declined as the histologic criteria utilized for treatment increased. CONCLUSIONS: A strategy in which inmates with chronic HCV are evaluated and a decision regarding treatment is based upon either biochemical or histologic criteria, which appears to balance both the health-care rights of the inmate and the impact of treating this disease on the financial and other resources of the correctional system.

Adult↗
PubMed2005

Predictors of candidate maturation among potential living donors.

The shortage of deceased donor allografts and improved outcomes in partial organ transplantation have led to widespread application of adult-to-adult living donor liver transplantation. Donor selection limits overall utilization of this technique and predictors of candidate maturation have been inadequately studied to date. We therefore collected data on 237 consecutive potential donors including their age, sex, ethnicity, relationship to the recipient, education, employment and religious beliefs and practices. Of these 237 candidates, 91 (38%) were excluded for medical and psychosocial reasons, 53 (22%) withdrew from the process predonation and 93 (39%) underwent partial liver donation. In multivariate analyses, the relationship between the donor and the recipient was highly predictive of successful donation. For pediatric recipients, no parents voluntarily withdrew from the evaluation process. For adult recipients, spouses are the most likely to donate, followed by parents, children and siblings. Additional predictors for donation included self-description as religious but not regularly practicing, part-time employment and higher education. Race, ethnicity, gender and age did not predict donation in multivariate analysis. Further understanding of the complex decision to donate may improve donation rates as well as permit more efficient and cost-effective donor evaluation strategies.

Adolescent↗
PubMed2005

Kidney and liver living donors: a comparison of experiences.

BACKGROUND: Living donor kidney transplantation is considered a safe and effective means to treat end-stage renal disease, and has now exceeded the number of deceased donor kidney transplantations performed annually. Living donor liver transplantation is more controversial and has received criticism in the medical and lay community. Studies focus on recipient outcomes and medical safety. The impact of the donation on donors is not well understood. OBJECTIVE: To compare experiences from both kidney and liver living donors, including their motivation, perceived risks, and postoperative experience. METHODS: Questionnaires about the donation experience were mailed to 70 patients who underwent laparoscopic donor nephrectomy and 85 patients who underwent hepatectomy at a large academic medical center. Results of kidney and liver donors were compared. RESULTS: No differences were found in mean age, marital status, ethnicity, relationship to the recipient, and employment status of the 2 groups. Women were more prevalent in both groups. The most common motivating factor in both kidney and liver donors was "because it was family," 81% and 82%, respectively. Kidney donors describe the decision to donate as easy compared to the liver donors (P = .049). In neither group did donors feel pressure to donate or have family conflicts regarding their decision to donate. Both groups felt they were well informed of the risks. Neither group described unexpected problems, and neither group regretted their decision to donate and would do it again if asked. CONCLUSION: Donors in both groups reported favorable outcomes. A greater concern for risk of death, bleeding, altered appearance, and infection existed among liver donors compared to kidney donors. The actual outcomes were better than the perceived risks.

Adult↗
PubMed2005

Role of the independent donor advocacy team in ethical decision making.

Adult living donor liver transplantation has developed as a direct result of the critical shortage of deceased donors. Recent regulations passed by New York State require transplant programs to appoint an Independent Donor Advocacy Team to evaluate, educate, and consent to all potential living liver donors. Ethical issues surround the composition of the team, who appoints them, and the role the team plays in the process. Critics of living liver donation have questioned issues surrounding motivation and the ability of donors to provide true informed consent during a time of family crisis. This article will address issues surrounding the controversies and discuss how using the team can effectively evaluate and educate potential living liver donors and improve practice to ensure safety of living donors.

Communication↗
PubMed2004

Characterization of the active site and insight into the binding mode of the anti-angiogenesis agent fumagillin to the manganese(II)-loaded methionyl aminopeptidase from Escherichia coli.

EPR spectra were recorded for methionine aminopeptidase from Escherichia coli (EcMetAP-I) samples (approximately 2.5 mM) to which one and two equivalents of Mn(II) were added (the latter is referred to as [MnMn(EcMetAP-I)]). The spectra for each sample were indistinguishable except that the spectrum of [MnMn(EcMetAP-I)] was twice as intense. The EPR spectrum of [MnMn(EcMetAP-I)] exhibited the characteristic six-line g approximately 2 EPR signal of mononuclear Mn(II) with A(av)((55)Mn)=9.3 mT (93 G) and exhibited Curie-law temperature dependence. This signal is typical of Mn(II) in a ligand sphere comprising oxygen and/or nitrogen atoms. Other features in the spectrum were observed only as the temperature was raised from that of liquid helium. The temperature dependences of these features are consistent with their assignment to excited state transitions in the S=1, 2 ... 5 non-Kramer's doublets, due to two antiferromagnetically coupled Mn(II) ions with an S=0 ground state. This assignment is supported by the observation of a characteristic 4.5 mT hyperfine pattern, and by the presence of signals in the parallel mode consistent with a non-Kramers' spin ladder. Upon the addition of the anti-angiogenesis agent fumagillin to [MnMn(EcMetAP-I)], very small changes were observed in the EPR spectrum. MALDI-TOF mass spectrometry indicated that fumagillin was, however, covalently coordinated to EcMetAP-I. Therefore, the inhibitory action of this anti-angiogenesis agent on EcMetAP-I appears to involve covalent binding to a polypeptide component at or near the active site rather than direct binding to the metal ions.

Aminopeptidases↗
PubMed2004

Microvascular hepatic artery anastomosis in pediatric segmental liver transplantation: microscope vs loupe.

Use of operative microscopy (OM) has dramatically reduced the incidence of hepatic artery thrombosis (HAT) in children undergoing segmental liver transplantation. We used OM (12-16x) in our early experience. We changed to high power loupe magnification (6x) after 14 cases. We examined our experience with microvascular hepatic artery reconstruction in 28 consecutive children (< 18 years) who underwent living donor (LDLT) or split liver transplantation (SLT). Reconstructions were done with interrupted, end-to-end anastomoses with 8-0 polypropylene using microvascular techniques. Group 1 consisted of 14 children who underwent LDLT employing OM for the hepatic artery anastomosis. Group 2 consisted of the subsequent 14 children (11 LDLT, 3 SLT) in whom 6x loupe optics were used for the arterial anastomosis. Grafts included 25 left lateral segments, 2 left lobes, and 1 right lobe. Recipients' median age was 1.0 years (range 3 months to 17 years). The mean follow-up time was 27.1 months. There were no cases of HAT. Variables of age, sex, graft type, number of Doppler ultrasound exams (DUS), and biliary complications were similar between groups. Microvascular hepatic artery reconstruction in children with 6x loupe magnification can yield results as good as operative microscopy.

Adolescent↗