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N L Ascher

Publications and source records attributed to N L Ascher.

At least 19 recordsLinked to original sources
PubMed1998

Single-center long-term results of renal transplantation for IgA nephropathy.

BACKGROUND: Previous reports with short-term follow-up after renal transplantation for IgA nephropathy (IgAN) have suggested an incidence of recurrence up to 50%, an increased recurrence with living-related donors, and the rarity of graft loss due to recurrence. In this study, the long-term results of renal transplantation for IgAN were examined. METHODS: Between June 1980 and December 1994, 54 patients (61 renal transplants) with end-stage renal disease due to IgA nephropathy were performed at the University of California San Francisco. Actuarial patient and graft survival were compared with a matched reference group. Correlates of recurrent disease (biopsy confirmed) and graft loss were determined. RESULTS: Patient and graft survival for IgA patients were good (100% and 75%, respectively, at 5 years after transplant). Graft survival was lower in IgA recipients with living-related compared with cadaveric renal allografts (P<0.09) and also with renal allografts well matched at HLA-AB (< or =2 AB mismatches) (P<0.09) or HLA-DR (< or =1 mismatch) (P<0.01). Recurrence was not correlated with donor status, recipient age, race, gender, or immunosuppression. Recurrence (18 of 61) resulted in substantial graft loss (6 of 18) or deteriorating renal function (4 of 18) at a mean follow-up of 61 months. Mean time to diagnosis of recurrence and subsequent graft loss was 31 and 63 months, respectively. Despite re-recurrence of IgAN in three of five patients who were retransplanted, all have good long-term renal function. CONCLUSIONS: Substantial graft loss due to recurrent disease after renal transplantation for IgAN occurs with long-term follow-up. Living-related transplantation and HLA matching do not appear to confer an advantage for graft survival in patients with IgAN. Despite the potential for recurrence, IgAN patients enjoy good long-term graft survival.

Actuarial Analysis↗
PubMed1998

Risks associated with conversion of stable patients after liver transplantation to the microemulsion formulation of cyclosporine.

BACKGROUND: Neoral is a microemulsion formulation of cyclosporine that has a better pharmacokinetic profile than the standard formulation (Sandimmune). To prove the safety of converting stable liver transplant patients from Sandimmune to Neoral, we conducted a prospective trial involving 54 patients. METHOD: The average time from transplantation to conversion was 48.5+/-21.6 months. Thirty of 54 patients (55%) required a dose reduction during the study for various reasons. Five of 30 patients had the first dose reduction because of increased levels of cyclosporine. Seven patients required more than one dose reduction. RESULTS: Sixteen patients suffered serious adverse events. Six patients had a biopsy-proven rejection. Four of 6 patients had trough cyclosporine levels within 20% of baseline value immediately before developing rejection. CONCLUSION: Converting patients from the standard formulation to the microemulsion formulation of cyclosporine seems to expose stable patients to unnecessary risks.

Adolescent↗
PubMed1998

Quo vadis, my transplant fellow: a discussion of transplant surgery fellowship training activity in the United States and Canada: 1991-1997. Education Committee of the American Society of Transplant Surgeons.

This is a discussion of transplant surgery fellowship training issues that pertain to educational quality guidelines of fellowship programs, the number of fellows being trained, and the individual's fate in securing transplant surgery positions after training. In 1995, the Council of the American Society of Transplant Surgeons (ASTS) revised the academic guidelines to enhance the educational standards of programs seeking ASTS approval as a transplant surgery fellowship training program. The criteria for accrediting training programs in kidney and liver transplant surgery were redefined, and new criteria for pancreas transplant surgery training were developed. Regarding the number of transplant surgery fellows being trained per year, during the period from 1991 to 1997, a total of 327 transplant surgery fellows completed training at ASTS-accredited transplant surgery fellowship training programs. The annual number of transplant surgery fellowship graduates has remained nearly constant at approximately 45 per year. However, the proportion of transplant surgery trainees who are foreign medical graduates has increased annually since 1995. Currently, 49% of the trainees are foreign medical graduates. Regarding the individual's fates in securing transplant surgery positions after training, the proportion of U.S./Canadian medical graduates who received transplant surgery training during the last year but are practicing in surgical disciplines other than transplant surgery appears to be increasing. Before 1996, it was rare for transplant surgery trainees to pursue surgical practice activities that did not include transplantation. Among the current group of 28 U.S./Canadian medical graduates who completed transplant surgery training between January 1997 and July 1997, six did not secure an acceptable position in transplantation. Instead, they are practicing in either general surgery or vascular surgery, or obtaining additional transplant training. These changes in the demographics and dynamics of transplant surgery fellowship training activity provoke important concerns.

Canada↗
PubMed1998

The role of pediatricians in the care of children with liver transplants.

OBJECTIVE: To examine the role of pediatricians in posttransplantation care of pediatric liver transplant recipients. DESIGN: Written survey of parents and pediatricians of children enrolled in a pediatric liver transplant program. SETTING: Questionnaires were mailed from a liver transplant center (LTC), set in a university-affiliated, tertiary-care medical center, to the homes of families and the offices of pediatricians in a variety of urban, suburban, and rural locales worldwide. STUDY POPULATION: Eighty-four percent of families and 81% of pediatricians who met study criteria participated. RESULTS: Only 8.9% of all pediatricians reported feeling comfortable providing all care for their liver transplant patients, while 82.2% were most comfortable sharing responsibility for care with the LTC. The remaining 8.9% of pediatricians were most comfortable with the LTC providing care. The more comfort pediatricians reported in providing care, the more likely parents were to report contacting pediatricians for medical problems. The more comfort pediatricians reported, the more parents perceived that (1) pediatricians and the LTC work well together (P<.03); (2) the LTC is informed about their child (P<.001); and (3) pediatricians are similarly up-to-date (P<.001). Furthermore, the more comfort pediatricians felt, the more parents believed that the liver transplant improved their child's health (P<.03) and that their child enjoys school (P=.08). Of the pediatricians, 15.6% who reported attending a continuing medical education course were significantly more comfortable (P=.05). The 18.9% of participating pediatricians who reported receiving some training in pediatric gastroenterology were also significantly more comfortable caring for children with liver transplants (P<.05). CONCLUSION: Increasing pediatrician comfort levels in providing posttransplantation care for children with liver transplants is critical to the continuing success of pediatric liver transplantation.

Attitude of Health Personnel↗
PubMed1998

Incidence and clinical consequences of surface and polymerase gene mutations in liver transplant recipients on hepatitis B immunoglobulin.

Mutations in the "a" determinant of the surface gene have been associated with failure of hepatitis B immunoglobulin (HBIg) prophylaxis. We compared sequences from the surface and polymerase regions of hepatitis B virus (HBV) from 4 patients who failed high-dose HBIg therapy with two control groups: HBIg-treated patients who remained hepatitis B surface antigen (HBsAg)-negative (n = 4) and HBV-infected transplant recipients who never received HBIg (n = 4). Mutations within the surface and overlapping polymerase region were more common in patients failing HBIg than controls (P = .03), and mutations in the region of the "a" determinant were present only in patients failing HBIg. To examine the relationship between HBIg failure and duration of therapy, five additional treatment failures from a second transplantation center were sequenced (total with HBIg failure = 9). Mutations in the "a" determinant developed in 1 of 3 patients receiving HBIg for less than 6 months compared with 5 of 6 patients failing HBIg after 6 months of therapy (P = .23). The most frequently identified amino acid substitution was glycine to arginine at position 145 (present in 4 of 6 patients who failed HBIg after at least 6 months of treatment). A unique mutation within the YMDD motif (methionine to leucine) was present in 1 patient who failed HBIg treatment and who received a short course of ganciclovir. We conclude that the emergence of mutations in the "a" determinant accounts for some, but not all, treatment failures in patients receiving HBIg prophylaxis. Mutations in other regions of the S gene were more common in patients failing HBIg than controls, suggesting that domains other than the "a" determinant may be important.

Adult↗
PubMed1998

Predictors of the cost of liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) is a highly effective but costly therapy for end-stage liver disease. However, there are limited data on the demographic and clinical variables that affect cost. We undertook a preliminary study using multiple regression techniques to analyze factors that influence the cost of OLT. METHODS: Patient and demographic data, including laboratory values and charges for all liver transplantations performed between June 1992 and June 1993 were analyzed (n = 111). Linear regression with standard and log-transformed values was performed by using STATA software (Stata Corporation College Station, TX). Independent variables included in the analyses were age, sex, United Network for Organ Sharing (UNOS) status, primary versus retransplantation, liver-kidney transplantation, and laboratory parameters of both liver (aspartate aminotransferase, AST; alkaline phosphatase; bilirubin; albumin; and prothrombin time) and kidney (blood urea nitrogen, BUN; creatinine) function. An F-to-remove strategy was employed with a significance level set at P = .05. RESULTS: The full model with 12 variables explained 37% of the total variation in charges. When one excludes variables that did not have a significant impact on cost, the remaining significant variables were BUN and UNOS status 1. The final model was Charges (US$) = 3,407 x BUN + 74,474 x status 1 + 102,662. This model accounted for 29% of the total variability with BUN accounting for the vast majority (26%). CONCLUSIONS: Renal function is the most important predictor of cost of OLT (P < .001). UNOS status 1 further increases cost, but other hospitalized patients have similar costs when one controls for other clinical variables. The degree of liver impairment is less important in predicting cost.

Adolescent↗
PubMed1998

Biliary complications of reduced-organ liver transplantation.

Reduced-organ liver transplantation for children is effective in lowering pretransplantation morbidity and mortality. Improvements in surgical technique have reduced vascular complications; however, biliary complications continue to account for significant posttransplantation morbidity. This investigation chronicles the incidence and type of biliary complications encountered with reduced-organ liver transplantation. Retrospective review of reduced-organ liver recipients over a 59-month period was performed, and biliary complications were classified as (1) missed biliary radicle, (2) anastomotic leak requiring revision, and (3) biliary stricture. From July 1992 to May 1997, 42 children received reduced-organ grafts: 32 living-donor, 8 cadaveric-reduced, 1 split-liver, and 1 auxiliary orthotopic liver transplant. Of the 42 grafts, 41 were Couinaud segments II/III and 1 was segments II/III/IV. Ten biliary complications were identified in 9 recipients (24%). Biliary complications included parenchymal radicle leaks, 5 (50%); biliary strictures, 3 (30%); and anastomotic leaks, 2 (20%). Although technical advances have reduced the incidence of biliary complications secondary to organ ischemia, parenchymal radicle leaks continue to be a source of morbidity for reduced-organ recipients. Planned exploration on posttransplantation day 7 was performed on the most recent 26 of the 42 total reduced-organ procedures as a mechanism to identify and treat early technical complications. Planned exploration as a routine component of reduced-organ transplantation has yielded a 15% incidence of discovered parenchymal leaks and a 5% incidence of discovered anastomotic leaks. This series underscores the necessity for improved anatomical studies to correctly identify duct territories and the development of accurate noninvasive methods to assess the biliary system preoperatively and intraoperatively in the application of reduced-organ liver transplantation.

Biliary Tract Diseases↗
PubMed1998

Hepatitis after liver transplantation: the role of the known and unknown viruses.

This study was designed to determine the cause of posttransplantation hepatitis in patients undergoing transplantation for liver disease of nonviral cause; the role of acquired hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis G virus (HGV) in posttransplantation hepatitis; and the course of posttransplantation hepatitis of unknown cause. Two hundred forty-three patients underwent transplantation for nonviral liver diseases (mean age, 48 years; 103 men, 140 women). Serological and virological assays for HBV and HCV were performed pretransplantation to exclude preexisting infection and posttransplantation to investigate the cause of posttransplantation hepatitis. Histology was graded on all available biopsy specimens; posttransplantation hepatitis was assessable in 150 patients. Posttransplantation hepatitis was present in 29% (44 of 150) of the patients after a median follow-up of 47 months (range, 1 to 101 months). Actuarial survival was significantly lower in patients with posttransplantation hepatitis compared with patients without (71% v 89% at 5-year follow-up; P = .03). HCV and HBV were identified posttransplantation in 14% and 9% of patients with hepatitis, respectively. After the exclusion of HCV and HBV infection, 22% (33 of 150) of the patients had posttransplantation hepatitis of unknown cause. HGV was present in 58% of these patients, but HGV was equally prevalent in patients without posttransplantation hepatitis. When patients with HBV and HCV were excluded, there was no difference in survival between patients with posttransplantation hepatitis compared with patients without (P = .08, log-rank test). Posttransplantation hepatitis was present in approximately 30% of the patients undergoing transplantation for nonviral diseases, with a median follow-up of 47 months. Known hepatitis viruses (HBV, HCV) were present in one fourth of the patients with posttransplantation hepatitis; 22% (33 of 150) of the patients had hepatitis of unknown cause, suggesting that other, as yet undiscovered, hepatitis viruses may exist.

Adult↗
PubMed1998

Hepatic artery pseudoaneurysm with hemobilia following angioplasty after liver transplantation.

A 58-yr-old female with primary biliary cirrhosis underwent an uncomplicated orthotopic liver transplantation. Elevated liver function tests 2 months post-transplantation were evaluated with Doppler ultrasound and a hepatic artery stricture was documented. The hepatic artery stenosis was treated with angioplasty. She developed hemobilia 1 d after the procedure, which was confirmed by angiography. Emergent exploratory laparotomy revealed a pseudoaneurysm at the hepatic artery anastomosis. The pseudoaneurysm was resected and the proper hepatic artery of the graft was anastomosed to the splenic artery of the host using preserved homograft. Her post-operative course was uneventful and liver function tests returned to normal quickly after the surgery. This report will discuss the unusual nature of this complication, and review the problem of hemobilia and pseudoaneurysms in liver transplant recipients.

Anastomosis, Surgical↗
PubMed1997

A controlled analysis of the transjugular intrahepatic portosystemic shunt in liver transplant recipients. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplantation Database.

BACKGROUND: The transjugular intrahepatic portosystemic shunt (TIPS) is an important treatment for complications of portal hypertension. As some authors have suggested that TIPS may facilitate liver transplantation technically, the objective of this study was to determine the impact of TIPS on the liver transplant operation and its outcome. METHODS: The analysis was designed as a retrospective cohort study using a multicenter database. Fifty-five patients with TIPS were matched with 55 controls on the basis of 10 pretransplant laboratory, clinical, and demographic features. TIPS patients and control patients were compared with regard to duration of surgery, intraoperative blood product usage, liver and renal function, volume of ascites, survival, and hospital stay. For confirmatory purposes, a parallel analysis using linear regression methods was performed. RESULTS: By matched analysis, TIPS patients had less ascites at surgery (mean 0.9+/-0.20 vs. 2.2+/-0.37 L, P=0.005) and a slightly shorter time from incision to cross-clamp (mean 2.1+/-0.10 vs. 2.5+/-0.15 hr, P=0.03). However, there were not significant differences for total operative time (mean 6.0+/-0.17 vs. 6.3+/-0.25 hr, P=1.00), blood product usage, or any other outcome variable. Regression analysis confirmed these results. CONCLUSIONS: TIPS does not significantly impact the course of liver transplantation surgery. Therefore, preoperative portal decompression solely to facilitate liver transplantation is not an appropriate indication for TIPS.

Cohort Studies↗
PubMed1997

Antibody to the host cellular gene-derived epitope GOR-1 in liver transplant recipients with hepatitis C virus infection.

The presence of anti-GOR was determined in paired pre-orthotopic liver transplantation (pre-OLT) and post-OLT sera from 87 OLT patients with hepatitis C virus infection. Before OLT, 48/87 patients were seropositive for anti-GOR, but this marker had no relationship with the clinical and biochemical parameters, or viremia level. Anti-GOR was less commonly detected in patients infected with genotype 3a, compared with genotypes 1 and 2, which might be related to the less conserved nature of the proposed shared epitope (amino acid sequence 9-18) in genotype 3a isolates. After OLT (median follow-up 16 months), anti-GOR was detected in 31/87 patients and it had no correlation with the clinical and biochemical parameters, viremia level, histologic disease activity, and clinical outcome. Changes in anti-GOR status (before OLT versus after OLT) were also not related to any of the clinical parameters. Although anti-GOR is commonly detected in OLT patients infected with hepatitis C virus genotypes 1 and 2, it has no clinical or prognostic significance.

Adult↗
PubMed1997

Planned exploration of pediatric liver transplant recipients reduces posttransplant morbidity and lowers length of hospitalization.

BACKGROUND: Pediatric liver transplantation (eg, orthotopic liver transplantation) has been associated with decreased graft survival compared with adult transplantation; this has been attributed to the increased difficulty of the procedure in small children and the increased number of technical variants that have been used to increase the supply of small livers. OBJECTIVES: To adopt a policy of planned exploration (PLANEX) of children on the seventh day after orthotopic liver transplantation, to obtain a liver biopsy specimen, to identify and treat potential technical problems at that time, and to evaluate the effect of this strategy on the length of hospitalization and morbidity rate in 60 children who underwent orthotopic liver transplantation. DESIGN: The PLANEX was adopted progressively during a 3-year period. A retrospective study was conducted that compared outcomes between patients who did and did not undergo PLANEX. Data were collected from chart review with a complete follow-up of patients. SETTING: A university medical center at which 130 liver transplantations are performed annually in adults and children. PATIENTS: Sixty children who received primary transplants between October 1992 and December 1996 were studied. INTERVENTIONS: Standard, partial, and living-donor transplantations were performed. Routine procedures performed at PLANEX included hematoma evacuation, tissue culture, inspection of all anastomoses, intraoperative ultrasonographic verification of vessel patency, open liver biopsy, and definitive abdominal closure. MAIN OUTCOME MEASURES: The duration of the primary hospitalization was the main outcome measure. Surgical complications and graft and patient survival rates were also analyzed. RESULTS: The mean +/- SD length of hospitalization for 24 recipients who underwent PLANEX was 16.5 +/- 5.7 days compared with 19.2 +/- 4.7 days for 6 patients (25%) who had significant findings at exploration (P = .34). In the 36 patients who did not undergo PLANEX, 10 patients (28%) required unplanned explorations (on median posttransplant day 13) that identified the following 13 complications: biliary (n = 4), undiscovered enterotomy (n = 6), hemoperitoneum (n = 2), and partial vascular thrombosis (n = 1). The mean length of hospitalization for recipients who did not require exploration was 19.3 +/- 3.9 days (PLANEX, P = .28); however, in patients who required unplanned exploration, the mean length of hospitalization increased to 41.2 +/- 15.5 days (median, 43 days). The mean length of hospitalization of recipients who underwent unplanned exploration was significantly increased compared with recipients who underwent PLANEX with significant intraoperative findings (P = .02). CONCLUSIONS: In this series, early identification and repair of surgical problems in asymptomatic patients on day 7 significantly decreased the hospital stay and morbid consequences of surgical problems. This aggressive approach may improve overall graft and patient survival.

Adolescent↗
PubMed1997

The impact of surgical complications after liver transplantation on resource utilization.

OBJECTIVE: To evaluate the impact of surgical complications on length of stay and hospital charges after liver transplantation. DESIGN: A retrospective economic evaluation of the outcomes during initial hospitalization after liver transplantation. SETTING: University hospital treating referred patients. PATIENTS: The study population was 109 patients undergoing 111 liver transplantations during fiscal year 1993. MAIN OUTCOME MEASURES: Hospital charges and length of stay during the initial hospitalization after liver transplantation. Multivariate regression methods were used to analyze the impact of surgical complications on costs. RESULTS: Of the 111 transplantations, 30 (27%) had a surgical complication that required a return to the operating room during the initial hospitalization. The effect of a surgical complication was to increase the mean hospital charges (excluding physician charges) from $150,092 to $347,728 (difference of mean, $197,636; confidence interval of difference, $114,153 to $319,326). The median length of stay was 16 days for patients without complications and 45 days for those with complications. Univariate and multivariate models suggested that surgical complications had the greatest effect on length of stay and hospital charges among the factors studied. Complications tended to occur more frequently among patients with United Network for Organ Sharing (UNOS) status 1 (42% vs 22%), but this did not reach statistical significance (P = .09). CONCLUSIONS: Surgical complications after liver transplantation have a marked impact on the cost of the procedure. The magnitude of this effect is greater than that of UNOS status, presence of rejection, or other demographic or clinical factors studied. Complications tend to occur in the most ill patients. Identifying strategies to reduce the risk of complications, particularly in patients with UNOS status 1, likely can reduce the cost of transplantation.

Adolescent↗
PubMed1997

Hepatitis G virus in patients with cryptogenic liver disease undergoing liver transplantation.

To examine the prevalence of hepatitis G virus (HGV) in end-stage liver disease of unknown cause and the role of HGV infection in posttransplantation hepatitis, we studied 46 patients undergoing liver transplantation (mean age, 50 years; M:F, 18:28) with cryptogenic cirrhosis. HGV RNA was detected by polymerase chain reaction (PCR) and was quantified by a branched DNA (bDNA) assay. The prevalence of HGV RNA was determined in samples collected before and after liver transplantation and was found to be 22% and 67%, respectively. We evaluated the prevalence of posttransplantation hepatitis in 25 patients, 16 of whom were HGV-positive and 9 were HGV-negative. The proportion of patients with hepatitis was not significantly different in the two groups (38% in HGV-positive and 22% in HGV-negative patients). The median histological scores were significantly higher in liver biopsies from patients with HGV infection than in those without HGV infection (2 [range, 0-14] and 1 [range, 0-3]; P = .01), but the histological scores were low overall. The duration of follow-up was similar in the two groups. HGV RNA levels were not correlated with the severity of liver disease based on histological score (r = -.08). Graft survival and patient survival were not significantly different. We concluded that liver disease was frequent (32%) after transplantation in patients with a pretransplantation diagnosis of cryptogenic cirrhosis, although the disease was generally mild. Although HGV RNA was demonstrable in the majority (67%) of patients after transplantation, there was no relationship between the presence of HGV RNA and the presence of posttransplantation liver disease. The finding of posttransplantation hepatitis in the absence of known viruses (A-G), suggests that other, as-yet-unidentified viruses may be important.

Adult↗