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Biomedical subjects

E Walter

Publications and source records attributed to E Walter.

At least 19 recordsLinked to original sources

[Gallstones: etiology and risk factors].

Cholesterin is excreted into bile together with phospholipids and bile acids, which are essential for the formation of micelles. Cholesterin-supersaturation of the bile and a relative hyposecretion of bile acids, the presence resp. the lack of promotors and inhibitors of nucleation and a reduced gallbladder contractility are the most important factors in the formation of cholesterol stones. For the formation of pigment stones, however, an increase of bilirubin production and infection of the biliary tract are the causative factors.

Bile

[Early diagnosis of hepatocellular carcinoma].

In every patient, in particular males of all ages presenting with chronically progressive diseases or cirrhosis of the liver, ultrasonography and an AFP test should be performed at intervals of six months. If hepatocellular carcinoma of the liver (HCC) is suspected (i.e. by increase of AFP or a positive result in ultrasonography), diagnosis should be confirmed by further investigations such as fine-needle biopsy guided by sonography, angiography and CT-scan. Adequate therapeutical measures such as resection of the tumor, chemotherapy, injection of alcohol or liver transplantation can thus be initiated in time. Besides efforts for early diagnosis of carcinoma of the liver, preventive measures (vaccination for hepatitis B, restrictive use of blood transfusion, reduction of alcoholism, thorough therapy of hemochromatosis, etc.) may contribute to the reduction of chronic diseases of the liver and of associated HCC.

Carcinoma, Hepatocellular

[Hepatitis A to E: current diagnosis].

Diagnosis of viral hepatitis is based on epidemiologic data (information about travels, blood transfusions, contacts with persons suffering from hepatitis, etc.) and on results of physical examination and laboratory investigations. Usually, serologic and genomic analysis lead to the specific proof of the viral etiology: HAV, HBV/HDV, HCV and HEV. If these infections are not detected, nonviral causes of hepatopathy should be investigated (i.e. toxic, pharmaco-toxic, metabolic, immunologic, etc.).

Hepatitis Antibodies

HIV-1 sensitivity to zidovudine and clinical outcome in children.

In adults with the acquired immunodeficiency syndrome, long-term monotherapy with zidovudine selects for human immunodeficiency virus type 1 (HIV-1) strains with substantially reduced in-vitro susceptibility to the drug. We have assessed the relation between in-vitro resistance to zidovudine and clinical outcome in children, in whom disease progression is more rapid than in adults. We studied 23 children with symptoms of HIV-1 disease during extended monotherapy with zidovudine. An in-vitro assay was used to determine the concentration of zidovudine required to inhibit by 50% the replication of viral isolates (IC50) obtained after 9 to 39 months of treatment. Viral stocks of high enough titre to yield reproducible results were obtained from 19 of the children. During the following 6 months of therapy, 9 children were stable, 7 deteriorated, and 3 died. There was a highly significant relation between decreased zidovudine susceptibility and poor clinical outcome (p less than 0.001) but no relation between IC50 and age at start of therapy or length of time on treatment. Age-adjusted CD4 lymphocyte counts were lower at the start of treatment (p = 0.02) and at the time of sampling (p = 0.01) in children whose viral isolates had an increased zidovudine IC50. Initial serum p24 antigen levels were not predictive of subsequent emergence of resistant virus, but at the time of sampling for viral sensitivity higher p24 antigen levels were associated with raised IC50 (p = 0.004). The findings suggest that most children who become unresponsive to monotherapy with zidovudine, as judged by clinical criteria, will have changes in in-vitro sensitivity to the drug. In these children, an alternative antiretroviral therapy should be considered.

Acquired Immunodeficiency Syndrome

Inhibition of duck hepatitis B virus infection by lysosomotropic agents.

The early phases of hepadnaviral infection were studied in primary duck hepatocyte cultures. Incubation of duck hepatocytes in vitro with duck hepatitis B virus (DHBV) resulted in infection with high levels of viral replication. The lysosomotropic agents ammonium chloride and chloroquine effectively inhibited viral infection, indicating that DHBV infection, similar to infection with other enveloped viruses, depends on receptor-mediated endocytosis and involves membrane fusion triggered by low pH.

Ammonium Chloride

[Correspondence of mammographic and pathological-anatomical tumor extent in breast cancer].

Pre-operative mammograms and exact information on the pathological-anatomical extent of the tumour were available in 198 patients with carcinoma of the breast. The tumour as seen on the mammogram was measured and compared with the histological information. Five of the 198 carcinomas (2 1/2%) could not be seen on the mammogram. In 69.7% of cases, mammography was suspicious of a carcinoma and in 27.8% a lesion was found that required further investigation. In 67.7%, the mammographic and pathological tumour extent agreed within 3 mm. In 18.2% the tumour appeared more than 3 mm greater, and in 9.6% more than 3 mm smaller than real size; the error was greater than 30 mm in only 3.2%.

Adult

Duck hepatitis B virus infection of non-hepatocytes.

One hundred and seventeen ducklings, 42 inoculated with duck hepatitis B virus (DHBV) 2 days after hatching and 55 connatally infected, were studied over a 6-month period in parallel with 20 ducklings without DHBV infection. Using immunohistochemical, in situ and blot hybridization analyses, the natural course of hepatic and extrahepatic infection was examined. DHBV infection started in the liver 2-4 days post-inoculation. There, DHBV was found not only in hepatocytes, but also in bile duct epithelial cells. Further, DHBV infection occurred in exocrine and endocrine pancreas (beginning 6-10 days and 20 days post-inoculation, respectively) and in germinal centers of the spleen (beginning 8 weeks post-inoculation). Occasionally viral DNA was also found in kidney glomeruli. Using strand-specific RNA probes, viral DNA in pancreas and spleen was clearly demonstrated to be replicating intermediates. Hepatic and extrahepatic infection with DHBV was not associated with histologic inflammation or pathologic changes in these tissues or the liver. These data indicate that DHBV can infect cells other than hepatocytes. The biological significance of non-hepatocyte infection for the life-cycle of the virus and its potential significance for viral persistence remain to be determined.

Animals

Sulfated polyanions do not inhibit duck hepatitis B virus infection.

On the basis of the antiviral action of sulfated polyanions in human immunodeficiency virus and other viral infections, we studied the effect of dextran sulfate and heparin on duck hepatitis B virus infection. These agents do not affect viral uptake and replication in liver cells in vitro or in vivo. Sulfated polyanions, therefore, appear to have no potential for the treatment of hepadnavirus infections.

Animals

Fate of interleukin-6 in the rat. Involvement of skin in its catabolism.

Iodinated recombinant human interleukin-6 (125I-rhIL-6) was intravenously injected into rats and its fate was studied during 24 h. Between 10-20 min after a single-dose injection, 125I-rhIL-6 accumulated in liver as previously reported [Castell et al. (1988) Eur. J. Biochem. 177, 357-361]. After 1 h, the radioactivity disappeared from the liver and accumulated in skin, reaching 35% of injected 125I-rhIL-6 5-8 h after injection. No comparable accumulation of radioactivity was found in skin when [125I]iodide or rat serum 125I-albumin was administered. Finally the radioactivity was detected as [125I]iodide in urine. Autoradiographic analysis of skin sections 5 h after 125I-rhIL-6 injection showed radioactivity in the interstitium. When the experiments were carried out with [35S]rhIL-6, essentially the same results were obtained: a decrease in radioactivity in the liver after 20 min, and a substantial increase in skin 7 h after injection. In vitro experiments showed that 125I-rhIL-6 is degraded by rat and human fibroblasts, whereas no degradation was observed with rat hepatoma cells (Fao) or human hepatocytes. These observations suggest the involvement of skin in the catabolism of IL-6.

Animals

[Chronic hepatitis B: diagnostic value of hepatitis-B-virus DNA analysis in serum and liver tissue].

The diagnostic value of hybridization analyses for the detection of hepatitis B virus (HBV) DNA in serum and liver tissue was investigated in 79 patients with chronic liver disease. Active viral replication was demonstrated by the detection of HBeAg or HBV-DNA in serum or liver tissue. However, HBV-DNA was also detected in the absence of HBeAg in serum. No correlation was found between the presence of HBV-DNA in serum or liver tissue and clinico-chemical or histological disease. In HBsAg-negative patients no HBV-DNA was detected in serum or liver tissue. These data indicate that serological markers are sufficient for the diagnosis of HBV infection. However, detection of HBV-DNA in serum or active viral replication in liver tissue is important in selecting patients for antiviral therapy (e.g. interferon) and monitoring its efficacy.

Adolescent

Long-term follow-up of posttransfusion and sporadic chronic hepatitis non-A, non-B and frequency of circulating antibodies to hepatitis C virus (HCV).

The natural course of chronic hepatitis non-A, non-B (HNANB) was documented for 3-20 yr (mean 8 yr) in 86 patients, who attended our special ambulance between 1981 and 1988. Sixty five of the 86 patients (75%) were positive for circulating antibodies against hepatitis C virus (HCV) (anti-HCV). Twenty four patients had chronic posttransfusion (PT)-HNANB (18 anti-HCV-positive; 75%), and 62 patients had sporadic (S)-HNANB (47 anti-HCV-positive; 75%). Twenty nine per cent of patients with chronic PT-HNANB had sustained normalization of aminotransferases after a period up to 5 yr, 55% demonstrated chronic persistent hepatitis (CPH) and 16% progressed to chronic active hepatitis (CAH) with transition to cirrhosis. In the group with chronic S-HNANB, 2% of patients showed remission, 43% had stable CPH and 55% progressed to CAH or cirrhosis. However, development of cirrhotic complications required many years. Transition from CAH to CPH or remission was not observed. The results indicate that 75% of both patients groups with chronic PT- and S-HNANB are infected with the same agent, of which antibodies are detected by the new anti-HCV assay. There was no statistical association between the severity of the disease and the presence of anti-HCV. The different proportions of progressive courses in chronic PT- and S-HNANB might be explained by the patient recruitment.

Blood Transfusion

[Non-cirrhotic portal hypertension].

A chronic increase of the portal venous pressure is not only a sequel of liver cirrhosis. There is a large group of different diseases leading to "non-cirrhotic portal hypertension". Clinical presentation, diagnosis and treatment are discussed. The discrimination between cirrhotic and non-cirrhotic portal hypertension is important for the understanding of differences in clinical signs and course of the diseases, however.

Arteriovenous Fistula

[Spontaneous remission of lung metastases in renal cell carcinoma].

Pulmonary metastases were first noted in a 47-year-old man, 15 months after a radical right nephrectomy and local radiotherapy. They progressed over the subsequent ten months despite progestagen administration. But they regressed slowly after the progestagen had been discontinued so that eight months later they were no longer demonstrable radiologically. The remission has so far persisted for 3 1/2 years.

Carcinoma, Renal Cell

Duck hepatitis B virus: cloning and subcloning of the viral genome.

In the course of studies on the biology of hepadnavirus infections, duck hepatitis B virus (DHBV) DNA was isolated from the serum of a German Pekin duck. Viral DNA was cloned in E. coli using pBR 322 DNA as a vector. The cloned DHBV DNA F 1-6 was characterised by restriction enzyme analyses. DHBV DNA F 1-6 was subcloned in both orientations in plasmid pSP 65 to produce strand-specific RNA probes. These probes specifically identified asymmetrically replicating nascent minus-strand DHBV DNA species or plus-strand viral RNA transcripts.

Animals

Plasma clearance, organ distribution and target cells of interleukin-6/hepatocyte-stimulating factor in the rat.

The plasma half-life of recombinant human interleukin-6 (rhIL-6) was determined in rats by measuring the disappearance of the biological activity as well as of the radioactivity of 125I-rhIL-6 from the circulation. The kinetics of clearance were biphasic. It consisted of a rapid initial disappearance corresponding to a half-life of 3 min, and of a second slow one corresponding to a half-life of about 55 min. By cellulose-acetate electrophoresis it was shown that rhIL-6 binds to a plasma protein resulting in a complex migrating in the beta-gamma region; 20 min after intravenous injection, about 80% of the 125I-rhIL-6 that had disappeared from the circulation was found in the liver. 125I-rhIL-6 was exclusively localized on the surface of parenchymal cells suggesting the existence of an interleukin-6 receptor on the hepatocytes.

Animals

Duck hepatitis B virus: DNA polymerase and reverse transcriptase activities of replicative complexes isolated from liver and their inhibition in vitro.

The duck hepatitis B virus (DHBV)-associated activities of reverse transcriptase and DNA polymerase and their inhibition in vitro were studied. Replicative complexes (RCs) were isolated from DHBV-infected liver by gel chromatography followed by sucrose gradient centrifugation. The RCs were detected by dot blot hybridization, using radiolabeled cloned DHBV DNA as a probe, and by the incorporation of 32P-TTP in the presence of dATP, dCTP, dGTP, and Mg2+ (endogenous DNA polymerase activity). The endogenous DNA polymerase activity associated with RCs was further studied using exogenous templates: reverse transcriptase and DNA polymerase activities were demonstrated using as substrates 32P-TTP and poly(rA) p(dT)12 or poly(dA) p(dT)12-18, respectively. Both activities were biochemically characterized. Their inhibition by various antiviral agents was studied in vitro: actinomycin D, ara-ATP, aphidicolin, suramin, chloroquin, and phosphonoformate. Among these, suramin, chloroquin, phosphonoformate, and ara-ATP were shown to be potent inhibitors of viral reverse transcriptase and DNA polymerase. Studies are now in progress to establish their antiviral activity in vivo.

Animals

[Conventional x-ray diagnosis of the knee joint following surgical repair of ligament injuries and after ligament replacement plasty].

Characteristic radiological findings following operative repair of the ligaments of the knee joint are described and related to the type of operative procedure. The operations depend on a number of basic principles which are discussed in detail. The majority of these surgical procedures are not apparent radiographically. It is only by having a knowledge of the individual procedures and of the resulting functional changes in the knee joint, that the informed radiologist can make a correct assessment of the post-operative radiographs. Defects resulting from bone drilling can be recognised tomographically in the early postoperative phase, or if they persist for any reason. This could be confirmed by experiments on pigs' knees.

Adolescent