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Biomedical subjects

R H Wiesner

Publications and source records attributed to R H Wiesner.

At least 217 records · Page 12Linked to original sources
PubMed1991

Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis.

Atraumatic fractures caused by osteoporosis may be a serious complication of primary biliary cirrhosis. Mean (+/- S.D.) bone mineral density in the lumbar spine in 210 ambulatory women with primary biliary cirrhosis was 1.02 +/- 0.19 gm/cm2, 7% lower than that in 139 age-matched normal women (after adjustment for age and body weight) (p less than 0.001). Bone mineral density in the lumbar spine was inversely related to a risk score index of liver disease severity (r = -0.29, p less than 0.001). The mean rate of bone loss in 105 of these 210 women was 2%/yr +/- 4%/yr, twice as great as in the 139 normal women (p less than 0.02). In 20 women with primary biliary cirrhosis followed up after orthotopic liver transplantation, bone mineral density in the lumbar spine decreased at 3 mo (p less than 0.01), and this decrease may have resulted in atraumatic fractures in 13 of them. Bone mineral density in the lumbar spine then increased (p less than 0.01) so that by 12 mo the median bone mineral density in the lumbar spine was similar to that before transplantation and by 24 mo it was 5% above it. Therefore we conclude that the progressive bone loss observed in primary biliary cirrhosis (which is further accentuated immediately after transplantation) may be halted, and the bone mass may be restored toward normal within 2 to 3 yr after orthotopic liver transplantation.

Absorptiometry, Photon↗
PubMed1991

Complications of liver biopsy in liver transplant patients: increased sepsis associated with choledochojejunostomy.

We investigated the incidence and types of liver biopsy complications in our first 160 consecutive liver transplantations. A significant complication was identified by the need for therapeutic intervention (for example, hospitalization, transfusion, intravenous fluids, chest tube, surgery or antibiotic therapy). A total of 950 percutaneous hepatic allograft biopsies were performed in 136 patients (mean = 6.9 biopsies/graft; range = 1 to 29). A significant complication was reported after 17 (1.8%) liver biopsies in 13 (9.6%) patients. Bleeding complications occurred in 11 patients and serious infection developed in 6 patients, but all patients recovered with appropriate therapy. Of special interest was that five of six patients with infectious complications had undergone Roux-en-Y choledochojejunostomy as part of the transplantation operation. The incidence of infectious complications related to a series of biopsies was significantly greater in patients who underwent choledochojejunostomy (12.5%) than in patients who underwent duct-to-duct biliary anastomosis (1%) (p less than 0.01). Furthermore, all septic events in patients who underwent choledochojejunostomy were related to enteric organisms. This investigation reaffirms the safety and low incidence of complications related to percutaneous liver biopsy even in this unique patient population. However, we did identify a subgroup of patients with biliary-enteric anastomoses who appear to be at increased risk of septic complications after liver biopsy. Antibiotic prophylaxis at the time of liver biopsy may be appropriate in this high-risk subgroup to decrease the frequency of infectious complications.

Adolescent↗
PubMed1991

The combination of prednisone and colchicine in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis is a cholestatic liver disease characterized by inflammation and fibrosis of the biliary tract. The cause of the disease is unknown, and no effective medical treatment exists. In this study, 12 patients received a combination of low-dose prednisone (10 mg/day) and colchicine (0.6 mg bid). Their course was compared with that of a group of concurrent historical controls. At 6 and 12 months, there was significantly more improvement in liver test results over baseline values in patients receiving prednisone and colchicine than in the untreated controls. At 24 months, however, no significant differences in biochemical tests were appreciated between treated and untreated patients. Analysis of serial liver biopsies showed no differences in histologic change in the two groups. During the 2 yr of follow-up, there were two deaths in the control group but none in the treated group. Four untreated patients developed ascites; gastrointestinal bleeding developed in three untreated patients, one of whom developed ascites. In contrast, in the treated group, ascites and bleeding developed in only one patient. We conclude that the combination of colchicine and prednisone does not retard histologic progression or progression of standard liver tests after 2 yr of therapy. There is a trend toward less clinical deterioration and improved survival after 2 yr of treatment. On the basis of these findings, we would not advocate empiric use of these drugs for patients with primary sclerosing cholangitis, but suggest that, if they are to be used at all in PSC, they be evaluated in a controlled clinical trial as treatment for this as yet incurable disease.

Adult↗
PubMed1991

Neutrophil cytoplasmic antibodies: a link between primary sclerosing cholangitis and ulcerative colitis.

Whether serum autoantibodies to neutrophil cytoplasmic components, previously found in ulcerative colitis, are also associated with primary sclerosing cholangitis was determined. In an enzyme-linked immunosorbent assay for immunoglobulin G neutrophil antibodies, neutrophil binding by primary sclerosing cholangitis sera was significantly greater than that for primary biliary cirrhosis, chronic hepatitis B, and chronic non-A, non-B hepatitis. Similar differences were seen when sera from patients with primary sclerosing cholangitis without evidence for ulcerative colitis were compared with sera from liver disease controls. Perinuclear immunofluorescence staining of neutrophils was exhibited by the majority of ulcerative colitis, primary sclerosing cholangitis, and primary sclerosing cholangitis without ulcerative colitis sera. The combination of elevated immunoglobulin G neutrophil antibodies and a perinuclear pattern was 65% sensitive and 100% specific for primary sclerosing cholangitis compared with the liver disease control sera. It is concluded that neutrophil cytoplasmic antibodies in ulcerative colitis and primary sclerosing cholangitis may be markers of shared underlying immunopathogenic mechanisms. Identification of the target antigen(s) may facilitate understanding of the underlying immune response and development of an improved disease marker assay.

Autoantibodies↗
PubMed1991

Acute fulminant hepatic failure.

Fulminant hepatic failure is the rapid onset of life-threatening hepatic decompensation in patients who have no previous history of liver disease. This condition has a multifactorial etiology, including viral hepatitis and drug toxicity. At this time there is no specific therapy for FHF. However, early diagnosis and treatment of the complications--in particular, cerebral edema--may prolong survival and prevent irreversible neurologic complications. Once the diagnosis has been made, patients with FHF should promptly be transferred to a specialized liver care unit where liver transplantation is available. Liver transplantation is now the treatment of choice for patients with clinical characteristics suggesting a poor chance of survival.

Acute Disease↗
PubMed1990

A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis.

Primary biliary cirrhosis is a progressive disease of the liver characterized by the immunologic destruction of bile ducts; effective therapy is lacking. We therefore evaluated the safety and efficacy of low-dose cyclosporine in 29 patients with primary biliary cirrhosis without evidence of damage to the lobular architecture (precirrhotic disease) or portal hypertension. The patients were randomly assigned to receive either cyclosporine (4 mg per kilogram of body weight per day) or placebo. After one year 17 of the 19 patients assigned to cyclosporine had improvement or stability in their degree of fatigue, and 18 in their degree of pruritus. In contrast, among the 10 patients assigned to placebo, fatigue increased in 4 (P less than 0.06) and pruritus worsened in 6 (P less than 0.001). Those assigned to cyclosporine also had significant decreases in serum levels of bilirubin, alanine aminotransferase, alkaline phosphatase, gamma globulin, and the titer of antimitochondrial antibodies. For the 20 patients who have completed two years in the study, liver biopsies (coded specimens) showed evidence of histologic progression in only 1 of 13 patients in the cyclosporine group, as compared with 5 of 7 in the placebo group (P less than 0.003). No patient has permanently discontinued cyclosporine because of side effects; however, signs of nephrotoxicity developed in 12 of 19, and 9 of 19 had increased blood pressure. We conclude that in patients with precirrhotic primary biliary cirrhosis, immunosuppressive therapy with cyclosporine is promising and deserves further evaluation.

Alanine Transaminase↗
PubMed1990

Early diagnosis of cytomegalovirus hepatitis in liver transplant recipients: role of immunostaining, DNA hybridization and culture of hepatic tissue.

Immunostaining techniques that use a monoclonal antibody against an early cytomegalovirus antigen or a polyclonal antibody, in situ DNA hybridization and inoculation of cell cultures for the detection of cytomegalovirus from liver biopsy specimens were studied in 20 liver transplant patients with cytomegalovirus hepatitis, as defined by histological criteria. A total of 108 liver biopsy specimens from 20 patients with a diagnosis of cytomegalovirus hepatitis (obtained per protocol at 7, 21, 90, and 180 days or whenever liver dysfunction occurred), which had previously been examined histologically and in cell culture, were again studied by recutting the liver tissue for histological examination, DNA hybridization and immunostaining with monoclonal or polyclonal antibodies to cytomegalovirus. In 5 of 20 patients, the diagnosis of cytomegalovirus hepatitis could have been made earlier (mean = 9.6 days) by immunostaining with a monoclonal antibody. Of 47 biopsy specimens with cytomegalovirus inclusion bodies, the sensitivity and specificity of the diagnostic procedures were immunostaining with monoclonal antibody (84% and 90%) and polyclonal antibody (72% and 97%), in situ DNA hybridization (72% and 100%) and cell culture detection (52% and 95%), respectively. Immunostaining with a monoclonal antibody against an early CMV antigen frequently detected cytomegalovirus infection in the liver allograft earlier than identification of typical histological inclusion bodies. DNA in situ hybridization was less sensitive than other techniques but highly specific; cytomegalovirus cell culture lacked sensitivity compared with the other procedures.

Adult↗
PubMed1990

The incidence of gram-negative bacterial and fungal infections in liver transplant patients treated with selective decontamination.

We have used selective bowel decontamination in 145 consecutive patients undergoing liver transplantation. In these 145 patients undergoing initial transplantation, we have experienced 42 major bacterial infections in 37 patients. Only five patients have experienced a gram-negative infection and only 2 of 26 documented bacteremias were associated with gram-negative organisms. To date, we have experienced only one systemic Candida infection. These results suggest that selective bowel decontamination may play a major role in reducing the previously reported high incidence of gram-negative and Candida sepsis following liver transplantation.

Bacterial Infections↗
PubMed1990

Advances in primary sclerosing cholangitis.

Primary sclerosing cholangitis is an increasingly recognized chronic cholestatic liver disease. It frequently occurs in association with chronic ulcerative colitis and is characterized by inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. The cause is unknown, although many mechanisms have been considered, including infectious, toxic, and immunologic. The prognosis varies. No adequate treatment exists, although a number of potential treatments have been evaluated in uncontrolled trials, and the results of controlled trials have only recently been reported. Liver transplantation has recently been shown to be an effective treatment for end-stage disease. These various advances in our understanding of primary sclerosing cholangitis are reviewed.

Cholangitis, Sclerosing↗
PubMed1990

Diminished survival in asymptomatic primary biliary cirrhosis. A prospective study.

Data from 73 asymptomatic patients with primary biliary cirrhosis were analyzed to determine clinical course and long-term survival. Of these, 44 entered a D-penicillamine treatment trial; 29 qualified but chose not to participate. Median follow-up was 7.6 yr (range, 2.8-12.2 yr). Liver biopsy at the initial visit showed advanced disease (fibrosis, cirrhosis) in 61% of the patients. During prospective clinical follow-up, which was available for 37 of the 44 study patients, one or more symptoms of liver disease developed in 33 (89%); esophageal varices were found in 15 (41%), and histologic progression to cirrhosis was found in 20 (67%) of the 30 precirrhotic patients. Significant (p less than 0.01) biochemical progression was reflected by a decrease in mean serum albumin concentrations and an increase in mean serum bilirubin levels in 32 patients followed for 4-6 yr. Survival data were available for all 73 patients; 17 died (11 secondary to liver failure), and 1 underwent liver transplantation. These patients had a 4-fold increase in mortality rate (p less than 0.001) compared with the U.S. population matched for age, race, and sex.

Adult↗
PubMed1990

Patients with asymptomatic primary sclerosing cholangitis frequently have progressive disease.

We identified and analyzed 45 patients with asymptomatic primary sclerosing cholangitis to better understand the natural history of this disease. Disease progression was monitored at regular intervals for the development of symptoms and physical signs as well as changes in liver biochemistry, cholangiography, and liver histology. During a median follow-up of 75.2 mo, 34 patients (76%) had evidence of disease progression. Fourteen patients (31%) developed liver failure which resulted in death or referral for liver transplantation. For patients with primary sclerosing cholangitis, survival curves computed using the Kaplan-Meier method were significantly worse than expected when compared to age-, sex-, and race-specific survival rates for the United States north central population (p less than 0.001). These findings indicate that primary sclerosing cholangitis is generally a progressive disease with considerable morbidity and mortality even when detected before the onset of symptoms.

Adult↗
PubMed1990

Applications of duplex ultrasonography in the liver transplant patient.

Duplex ultrasonography plays an important role in the preoperative and postoperative assessment of liver transplant patients. Before surgical intervention, the principal use of sonography is to assess the patency of the extrahepatic portal vein because a narrowed or thrombosed portal vein may preclude transplantation. Postoperatively, several potential complications can lead to allograft dysfunction (rejection, infection, vascular thromboses, and biliary tract complications). Because these complications often manifest with variable and nonspecific symptoms, diagnosing them can be difficult. Sonography is a valuable noninvasive means of evaluating postoperative complications in liver transplant patients. When vascular complications are suspected, duplex sonography is the optimal screening procedure for assessment of the vascular anastomoses. Focal parenchymal abnormalities (hematomas, infarcts, and bilomas) and localized collections of abdominal fluid are readily detected by ultrasonography and can be safely aspirated and, when infected, percutaneously drained under sonographic guidance. Sonography is less useful in the detection of biliary tract complications early after transplantation.

Humans↗