Search PubMed⌕ Search

Biomedical subjects

J Ludwig

Publications and source records attributed to J Ludwig.

At least 163 records · Page 9Linked to original sources
PubMed1991

Epstein-Barr virus and persistent graft dysfunction after liver transplantation.

Epstein-Barr virus infection has been associated with a broad spectrum of clinical manifestations, depending on the immune status of the host. In this report, we describe two liver transplant patients who received hepatic allografts from donors serologically positive for Epstein-Barr virus and who experienced primary infection with Epstein-Barr virus associated with prolonged liver graft dysfunction. In both patients, Epstein-Barr serologies converted within 3 mo of liver transplantation, and hepatic histological study revealed mononuclear infiltration of the sinusoids evolving to pronounced immunoblastic features suggestive of evolving lymphoma. In both cases, in situ hybridization studies confirmed the presence of Epstein-Barr virus genome in the liver. Furthermore, polymerase chain reaction analysis suggested that high levels of Epstein-Barr virus DNA were present in biopsy specimens obtained during the episode of acute hepatitis that followed Epstein-Barr virus seroconversion. The degree of Epstein-Barr virus DNA estimated by polymerase chain reaction appeared to increase in parallel with the progression of parenchymal lymphocytic infiltrates. In one patient, a biopsy sample from a cervical node also revealed high levels of Epstein-Barr virus DNA estimated using the polymerase chain reaction technique. Furthermore, in these patients, Epstein-Barr virus DNA levels appeared to decrease dramatically after discontinuing azathioprine administration and beginning treatment with acyclovir. These two cases illustrate the dynamics of Epstein-Barr virus immune regulation and confirm chronic hepatic allograft dysfunction related to Epstein-Barr viral infection.

Adult↗
PubMed1990

Primary structure of cAMP-gated channel from bovine olfactory epithelium.

The complete amino-acid sequence of the bovine olfactory epithelium adenosine 3',5'-cyclic monophosphate (cAMP)-gated channel has been determined by cloning and sequencing its cDNA. It exhibits a high degree of sequence homology with the cGMP-gated channel of rod photoreceptors, suggesting that cyclic nucleotide-gated channels fall into a new family of genetically related proteins.

Amino Acid Sequence↗
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 importance of plasma 3,4-dihydroxyphenylglycol (DOPEG) in analyses of the sympathetic nervous system in vivo.

In the anaesthetized rabbit, plasma DOPEG was used as a tool to estimate both, the total-body rate of neuronal re-uptake of noradrenaline (NA) and the factor F by which the NA concentration in the synaptic cleft exceeds that in plasma. The NA re-uptake rate was 3.5 times higher than the rate of NA net release into plasma and amounted to 863 pmol kg-1 min-1. F was 3.4. In a study in humans it was found that essential hypertension appears to be associated with an enhanced formation of that part of DOPEG which originates from NA leaking out of the transmitter storage vesicles.

Adolescent↗
PubMed1990

The synaptic noradrenaline concentration in humans as estimated from simultaneous measurements of plasma noradrenaline and dihydroxyphenylglycol (DOPEG).

A linear relationship between plasma DOPEG (ordinate) and plasma noradrenaline (NA; abscissa) was found during orthostasis as well as during NA infusion. The slope of the former (slopeR) was 13 times steeper than that of the latter (slopeI). This difference in slopes suggests that the NA concentration in the synaptic cleft is markedly higher than in plasma. The factor (F) characterizing this concentration difference was obtained from F2 = slopeR/slopeI. It amounted to 3.6.

Female↗
PubMed1990

Comparison of University of Wisconsin (UW) and Eurocollins (EC) preservation solutions in a rat liver transplant model.

The Eurocollins (EC) and University of Wisconsin (UW) preservation solutions were compared in a rat liver transplant model. After hepatectomy, 48 rat livers were flushed with either EC or UW preservation solution and were randomly assigned to 1, 12, 24, and 30 h of preservation at 4 degrees C, resulting in eight groups each containing six livers. Following preservation, orthotopic liver transplantation with reconstruction of the hepatic artery was performed. The efficacy of the preservation solution was assessed at 48 h post-transplantation by survival histological features and aspartate transaminase assay (AST) values. None of the rats survived 30 h of liver preservation with EC whereas five out of six rats did with UW preservation. After 24 h of liver preservation, three of the six rats in the EC group survived, compared to all six rats in the UW group. Histological evidence of severe ischemia was found in both groups in all but one survivor (UW, 24 h). After 12 h of EC preservation, one rat died within 48 h and severe ischemic changes were found in the remaining five rats. Among the rats with 12 h of UW preservation, only two out of six showed ischemic changes, and all six rats survived beyond 48 h. Without preservation (1 h), ischemic damage was found in two out of six rats in each group and all rats survived. The median AST values were higher in the EC groups than in the UW groups; the difference became significant after 12-h preservation (EC 900 IU/l versus UW 465 IU/l) and 24-h preservation (EC 5220 IU/l versus UW 631 IU/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
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

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

Classification of hepatic venous outflow obstruction: ambiguous terminology of the Budd-Chiari syndrome.

Severe hepatic venous outflow obstruction and its manifestations often are recorded under the label "Budd-Chiari syndrome." Unfortunately, this label is ambiguous; it does not clearly identify the site of the lesion (hepatic veins versus inferior vena cava), its morphologic features (thrombotic versus nonthrombotic), or its cause. In the literature, implied or expressed definitions vary. Use of a standardized topographic and pathogenetic classification of hepatic venous outflow obstruction would enable investigators to group patients with comparable conditions, as required for therapeutic trials, prognostic evaluations, and studies of pathogenetic pathways. Review of our own cases revealed that hepatic venous outflow obstruction involving large hepatic veins is usually thrombotic and that isolated obstruction of the inferior vena cava or of small hepatic veins is usually nonthrombotic. Application of such a classification seems feasible and may yield useful results.

Budd-Chiari Syndrome↗
PubMed1990

Persistent centrilobular necroses in hepatic allografts.

A biopsy study of 60 allografts from 53 patients after orthotopic liver transplantation (OLT) revealed prominent centrilobular necrosis (CN) in 18% of the grafts that were suitable for analysis. The lesions often had a "punched-out" appearance, sometimes with unusual features such as giant cell formation. Persistent CN developed 4 weeks to 6 months after OLT, and persisted in two cases for 2 years and longer. In some instances, CN disappeared or healed by scarring. We found no association between CN and rejection arteritis or arteriopathy. Ductopenic (chronic) rejection subsequently occurred in six of eight livers with CN. Overall, patients with persistent CN had a worse prognosis than control patients. A comparison of cases with matched controls failed to reveal significant differences with respect to perioperative factors such as ischemia time, immunologic test results such as lymphocyte crossmatches, drug administration--in particular, of azathioprine, frequency of cellular (acute) rejection or infection episodes, or frequency of complications affecting major hepatic vessels or bile ducts. Morphologic evidence suggests that in some instances, rejection-induced endotheliitis/phlebitis of hepatic vein branches may lead to sinusoidal outflow blockage, sinusoidal dilatation, and dropout of hepatic cell plates. Although potentially reversible conditions such as ischemia or adverse drug reactions are among the possible causes of CN, severe rejection leading to ductopenia appears to be the most important underlying condition. Thus, presence of CN in repeated biopsy specimens from allografts should be considered a warning sign of irreversible rejection.

Adult↗