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Biomedical subjects

H Bühler

Publications and source records attributed to H Bühler.

At least 55 records · Page 3Linked to original sources

[Whipple's disease with reactive (AA) amyloidosis].

A 59-year-old man had been known for two years to have a clearly elevated blood sedimentation reaction and intermittent arthralgia in the hand. His general condition had progressively deteriorated over the last six months, with weight loss, recurrent vomiting and constipation. At first malignant lymphoma had been suspected because numerous lymph nodes were enlarged. But a lymph-node biopsy revealed massive macrophages with PAS-positive inclusion material, diagnosed as Whipple's disease. The patient died suddenly of a heart attack on the day of diagnosis. At necropsy generalized amyloidosis with marked cardiac involvement was found. Immunohistochemically the amyloid deposits gave a strongly positive reaction to anti-AA, while other amyloid syndromes were excluded using appropriate anti-sera. This was therefore a case of reactive (AA) amyloidosis in the presence of Whipple's disease.

Amyloidosis↗

[Mesenteric panniculitis].

A 70-year-old patient with a 6 x 6 x 12 cm mass involving the mesentery root is discussed. The pseudotumorous infiltration was detected by ultrasound done because of nonspecific abdominal symptoms and weight loss. Laparoscopic biopsy confirmed the diagnosis of mesenteric panniculitis. The primary histologic criterion is infiltration of the mesenterium by foamy lipid-laden macrophages, clusters of lymphocytes and fibrosis. The majority of cases follow a benign course and need no therapy, but co-existence of lymphoma has been reported. There have been few cases where panniculitis with progressive fibrosis changed into retractile mesenteritis with shortening of the mesenterium and compression of mesenteric vessels with partial or complete intestinal obstruction or ischemia requiring surgery. Few reported cases of severe and progressive disease have been treated with prednisone and azathioprine or cyclophosphamide.

Aged↗

[Polymerase chain reaction in hepatitis C: increased sensitivity via amplification of shorter cDNA fragments].

The aim of our study was to compare the sensitivity of hepatitis C virus polymerase chain reaction (HCV-PCR) by use of two different primer sets which amplify PCR products of different length. Serum samples of 70 patients with chronic hepatitis C were tested by "nested primer" PCR, using either "NCR primers" that amplify cDNA-fragments of 340 basepairs (bp), or by "PT primers" which amplify fragments of 59 bp only. HCV-RNA was detected in 40 patients (57%) by "NCR primers" and in 69 patients (90%) by "PT primers" (p < 0.001). 23 of 70 patients (33%), which were HCV-RNA negative by "NCR primers", were positive by "PT primers", but no patient negative by "PT primers" was found to be positive by "NCR primers". 20 healthy controls tested by both primer sets were all HCV-RNA negative. We conclude that the sensitivity of HCV-PCR is significantly improved by use of primers that amplify "short" PCR products and recommend the use of "PT primers" for HCV-PCR.

Adult↗

[HIV-associated Penicillium marneffei infection].

We report on an HIV positive patient with a disseminated Penicillium marneffei infection. A 35-year-old Swiss homosexual male with HIV-associated immunodeficiency with a CD4 cell count of 90/mm3 presented with a two-month history of malaise, intermittent fever, loss of weight, unproductive cough and widespread molluscum contagiosum-like skin lesions, mainly on the face. The patient had travelled extensively and had last visited Thailand 19 months before admission. The chest X-ray showed bilateral diffuse reticulonodular markings. The diagnosis was suspected in bronchoalveolar lavage, which showed round-to-oval intracellular yeast cells but also elongated sausage-shaped extracellular forms. The diagnosis was confirmed on culture. Penicillium marneffei was further isolated from the following specimens: blood cultures, bone marrow, stool, skin and tracheal mucosa biopsy. Intravenous amphotericin B therapy led to a complete subsidence of all symptoms and the skin lesions healed without leaving a scar. The infection, with its clinical presentation, epidemiology, diagnostic problems and therapy is reviewed. We stress that since Penicillium marneffei is an increasingly important pathogen in HIV positive patients in Southeast Asia, this fungus can also be imported to Europe by travellers. If immunocompromised patients have molluscum contagiosum-like skin lesions, pneumonitis and a history of travelling in Southeast Asia, disseminated Penicillium marneffei infection should be considered in differential diagnosis.

AIDS-Related Opportunistic Infections↗

Low-dose interferon in chronic hepatitis non-A/non-B: effects on quantitative liver function and structure in a randomized, controlled multicenter trial.

In this randomized, controlled multicenter trial we evaluated the effects of recombinant interferon-alpha 2b on galactose elimination capacity and histological activity index in 88 patients with chronic active hepatitis non-A/non-B. Forty-five patients were randomly assigned to treatment with interferon at 1.5 x 10(6) U three times per for 1 year; 43 patients were assigned to no treatment. A complete response (normalization of alanine aminotransferase) was observed, respectively, in 47% and 5% of the two groups (P < 0.006); 47% of these patients suffered a relapse. Thus 22% of patients had a sustained response. Histological activity decreased significantly in responders (P < 0.04) while the biopsy score did not change significantly in nonresponders. In contrast, galactose elimination capacity--a surrogate marker for survival in chronic active hepatitis--was not affected by response to treatment. None of the parameters evaluated, including hepatitis C virus RNA, was able to predict response or relapse. We conclude that low-dose interferon treatment for 1 year is as effective as the recommended treatment schedule.

Adolescent↗

11-beta-Hydroxysteroid dehydrogenase of rat lung: enzyme kinetic, oxidase-reductase ratio, electrolyte and trace element dependence.

The modulation of the intracellular glucocorticoidal effect on surfactant synthesis of the fetal lung by the metabolic capacity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) could be an important factor in lung maturation. The kinetic properties of microsomal 11 beta-HSD of the rat lung are characterized with respect to product inhibition, substrate specificity, effect of electrolytes or trace elements, and the dependence of the oxidase reductase (OR) ratio on incubation conditions. With NADP+ product inhibition of the reductase was demonstrated. The most common trace elements and electrolytes exhibited no effect on the activity of 11 beta-HSD. It is shown that the OR ratio was strongly dependent on assay conditions. With optimal assay conditions oxidase activity exceeds reductase activity in adult and fetal rat lung microsomes (OR ratio > 1). Thus, glucocorticoids are mainly metabolized to their inactive forms. The enzyme activity in the adult is about 10 times higher than in the fetal lung. The low enzyme activity in fetal lungs could be the reason why the glucocorticoidal effects on surfactant synthesis are not suppressed despite the predominance of oxidase activity.

11-beta-Hydroxysteroid Dehydrogenases↗

Upper gastrointestinal hemorrhage preceding development of Bouveret's syndrome.

Gastric outlet obstruction by a gallstone is a very uncommon clinical entity; it was first reported by Bouveret in 1896. In the patient presented, we were able to show the development of formation of the bilioenteric fistula with massive arterial bleeding from the eroded cystic artery until duodenal occlusion. The process was endoscopically and radiologically observed and documented. Although the diagnosis was made immediately, the patient had to undergo surgery because the gallstone proved to be too large to be extracted endoscopically.

Aged↗

[Primary amyloidosis of the liver].

For 2 years a 72-year-old man had suffered from nonspecific upper abdominal discomfort and hepatomegaly. The gamma-glutamate transaminase concentration was increased to 121 U/l, the erythrocyte sedimentation rate was 80 mm in the first hour. Histological examination of tissue from the enlarged liver (22 cm in the midclavicular line) revealed the diagnosis of amyloidosis. The gastric mucosa, duodenum and rectum were not involved. Two years later ascites developed; six months after this he was again hospitalized in hepatic coma. Now, for the first time, a type IgA-lambda paraprotein was demonstrated by serum immunoelectrophoresis. The patient died of slowly progressing anicteric liver failure after having been ill for a total of 4 1/2 years. At autopsy there were extensive amyloid deposits throughout the liver and spleen so that the structure of these organs was hardly recognizable. The amyloid deposits in the liver were restricted to the glomerular region, while there was no amyloid in the heart. Histochemical tests showed that the deposits were strongly positive to the anti-lambda antibody. This was thus a case of primary (AL-lambda) amyloidosis of the liver and spleen which had taken an unusually prolonged course, because the heart was not involved at all and the kidneys only slightly.

Aged↗

[Heterosexual transmission of hepatitis-C virus].

Parenteral transmission of hepatitis C virus (HCV) through blood transfusions and intravenous drug misuse is well established. Since 50% of patients with hepatitis C have no history of parenteral exposure, other ways of transmission must exist. The purpose of this study was to examine the epidemiological importance of heterosexual intercourse for transmission of HCV infection. 29 heterosexual contacts (13 men, 16 women, mean age 47 years) of 29 index patients (16 men, 13 women, mean age 49 years) with histologically und serologically documented chronic hepatitis C were questioned about parenteral exposure and sexual behaviour. Their serum samples were examined for ALT activity and anti-HCV antibodies (first-generation Ortho-HCV-ELISA). Five contacts were using condoms to prevent infection. Five of 24 contacts (21%) practising unprotected sexual intercourse, but none of 5 contacts using condoms, showed evidence of heterosexual HCV transmission: 4 were anti-HCV positive (one with elevated ALT activity) and another showed elevated ALT activity with a negative anti-HCV test. None of these contacts had a history of parenteral exposure. Our results indicate that heterosexual transmission of HCV is epidemiologically important. The true rate of infection may be even higher, for two reasons: (1) not every HCV infection is detected by the anti-HCV test, and (2) the anti-HCV test may turn negative again in uncomplicated infection.

Adult↗

[Second generation hepatitis-C virus test and polymerase chain reaction in anti-C 100 negative patients with chronic non-A, non-B hepatitis].

The aim of our study was to evaluate whether a negative HCV test of the first generation (HCV-ELISA 1) using the antigen C100-3 excludes chronic HCV infection, or whether patients exist who are negative for antibodies to C100-3 in spite of chronic hepatitis C. 27 patients with histologically proven chronic non-A, non-B hepatitis, all of whom were HCV-ELISA 1 negative, were tested by the HCV test systems of the second generation (Ortho-HCV-ELISA 2 and Chiron-HCV-RIBA 2) based on the distinct HCV antigens 5-1-1, C100-3, C33c and C22-3. To determine the presence of viremia, serum samples were also tested for HCV-RNA with "nested" PCR. 10 of 27 patients proved to be persistently negative when tested with the second generation assays. One patient showed low grade reactivity by HCV-ELISA 2, but non-reactivity by HCV-RIBA 2. In none of these 11 patients was HCV-RNA detected. 16 (60%) of 27 patients negative with HCV-ELISA 1 were positive with HCV-ELISA 2. HCV-RIBA 2 detected antibodies to the structural core antigen C22-3 in all of these 16 patients and antibodies to the non-structural antigen C33c in 14 of them, while antibodies to 5-1-1 or C100-3 were not found in any of these cases. 10 (63%) of the 16 HCV-ELISA 1 negative, but HCV-ELISA 2 and HCV-RIBA 2 positive patients were positive for HCV-RNA by "nested" PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Hepatitis-C virus and hepatoma].

To clarify the relationship between hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC), frozen serum samples from 213 patients with histologically proven liver cirrhosis alone (96 alcoholics, 59 HBsAg positive, 29 non-A, non-B hepatitis, 29 cryptogenic) and 40 patients with liver cirrhosis and HCC (12 alcoholics, 7 HBsAg positive, 7 non-A, non-B hepatitis, 14 cryptogenic) were analyzed for antibodies to hepatitis C virus (anti-HCV) with the ortho-HCV-ELISA. The results were as follows. 50 of 253 (20%) patients were anti-HCV positive. The prevalence of anti-HCV was significantly higher in patients with HCC than in patients without HCC (14 of 40 [35%] vs 36 of 213 [17%]; p less than 0.001). In anti-HCV-positive patients HCC were significantly more frequent than in anti-HCV-negative patients (14 of 50 [28%] vs 26 of 203 [13%]; p less than 0.001). The significantly higher occurrence of HCC in anti-HCV-positive patients was not related to other known risk factors such as alcoholism or chronic hepatitis B virus (HBV) infection. Patients with HCV infection as the only risk factor also had a significantly higher occurrence of HCC (12 of 38 [32%] vs 26 of 203 [13%]; p less than 0.001). Our data suggest that chronic HCV infection plays an important role in the pathogenesis of HCC, in particular in patients with cirrhosis unrelated to alcohol or HBV infection.

Aged↗

[Anti-HCV test in patients with chronic non-A, non-B hepatitis].

Our study was designed to evaluate the clinical significance of the ELISA-anti-HCV test. 90 patients with histologically proven chronic non-A, non-B hepatitis (NANBH) and a control group consisting of 36 patients with primary biliary cirrhosis (PBC) were analyzed for antibodies to hepatitis C virus (anti-HCV). Frozen serum samples were tested with the ortho-HCV-ELISA. 67 of 90 (74%) patients with chronic NANBH showed antibodies to the hepatitis C virus. The prevalence of anti-HCV in patients with parenterally transmitted and sporadic chronic NANBH was 70% (23 of 33) and 77% (44 of 57) and in patients with chronic active and chronic persistent NANBH 73% (27 of 37) and 76% (40 of 53) respectively. No significant difference in the prevalence of anti-HCV in the 4 subgroups of patients with chronic NANBH was found. 2 of 36 patients (6%) with PBC were anti-HCV positive without evidence of previous HCV infection. Our results bear out the experience of other authors, that HCV is the commonest pathogen of chronic NANBH. The low prevalence of anti-HCV in patients with PBC suggests good specificity. There have been reports in the literature of "false positive results", particularly in autoimmune hepatitis, and it has been shown that borderline positive test results are often unspecific and therefore to be interpreted with care.

Adult↗

[The endoscopic treatment of malignant biliary tract stenoses with endoprostheses].

In 65 patients (36 men, 29 women; mean age 74 [43-90] years) obstructive jaundice caused by malignant biliary stenosis was treated by endoscopic retrograde insertion of a 10 or 12 F synthetic endoprosthesis. The rate of complications of the endoscopic intervention was 5% (n = 3), 30-day mortality rate was 11% (n = 7) and method-related mortality was 8% (n = 5). Good drainage was achieved in 39 of 41 patients (95%) with the 12 F endoprosthesis, and in 15 of 21 patients with a 10 F one (71%) (P less than 0.001). Renewed jaundice due to prosthesis occlusion occurred in 31 patients an average of 103 (11-350) days after placement. Interval until occlusion correlated with the site of the stenosis and the length of the endoprosthesis. Jaundice recurred earlier in patients with long prostheses and proximal biliary stenosis than in those with a short prosthesis and distal stenosis. In 20 patients with renewed jaundice the endoprosthesis was replaced endoscopically. At that time 13 of the patients had a cholangitis. Occlusion of the new endoprosthesis was more common in patients with cholangitis (9 of 13) than those without (2 of 7; P less than 0.05). These findings indicate that endoscopic biliary tract drainage should be performed with as short a 12 F endoprosthesis as possible. In view of the potential need for early change of endoprosthesis the biochemical parameters of cholestasis should be regularly monitored.

Adult↗

Polymerase chain reaction detects hepatitis B virus DNA in paraffin-embedded liver tissue from patients sero- and histo-negative for active hepatitis B.

The polymerase chain reaction (PCR) was used to analyse tissues from paraffin blocks of liver needle biopsies retrospectively. Biopsies of 29 patients with proven HBsAg and HBcAg expression in liver tissue and of 8 healthy volunteers served as positive (group 1) and negative tissue controls (group 2), respectively. These were compared with 16 patients with proven HBsAg expression in liver but lack of HBcAg (group 3), with 23 patients with anti-HBc as the only hepatitis B virus (HBV)-related marker (group 4) and with 21 patients with liver disease and without HBV markers in tissue or serum (group 5). PCR detected HBV sequences in all cases of the positive control group and in 94% of group 3, in 65% of group 4, and in 71.4% of group 5, whereas all healthy volunteers were negative. Our data show that PCR is able to detect HBV-DNA sequences in virtually all patients with active viral antigen expression but also in a high proportion of hepatitic patients who are silent for active HB but may or may not show signs of a contact with the HBV. Thus, PCR for HBV-DNA in paraffin sections might become a useful tool for identifying patients carrying HBV-DNA but not expressing HBV antigens.

Base Sequence↗

Inhibition of rat renal 11 beta-hydroxysteroid dehydrogenase by steroidal compounds and triterpenoids; structure/function relationship.

Various compounds with steroidal structure were tested for inhibitory effects on enzymatic activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) from rat renal microsomes. Most substances exerting inhibitory potency on both the oxidative as well as the reductive activity can be classified into two main groups: pentacyclic triterpenoids of the oleane type and steroidal detergents of the CHAPS-series. Inhibition is competitive, as was shown for one compound of each group. The IC50 values of the various inhibitors range over five orders of magnitude. In all cases, oxidative activity was inhibited more effectively than reductive activity. An attempt has been made to correlate structural properties and inhibitory potency. In brief, inhibition seems to be enhanced by a C11-oxygen function, which is present in all endogenous glucocorticosteroids and a C7-OH function. Inhibition is reduced by a large and polar substituent at C3 in the A-ring. A large D-ring substituent, such as a bisgluconamidopropyl side chain or even an additional E-ring, does not prevent binding to the enzyme, although inhibition seems to be influenced by its steric conformation. The cardiac glycosides and steroidal antibiotics tested exert no inhibitory effect on 11 beta-HSD. Cholesterol and pentacyclic triterpenoids of the lupane type exhibit a very poor inhibition, probably caused by the localization of planar structures in the ring systems, which differs from that of the effective oleane type inhibitors.

11-beta-Hydroxysteroid Dehydrogenases↗

[Non-A, Non-B hepatitis: advances in diagnosis and therapy].

The characterization of the hepatitis C virus (HCV) and the development of an anti-HCV antibody test have closed a further gap in the etiological diagnosis of viral hepatitis, but at the same time new questions have been raised. It has been shown that HCV is by far the most frequent source of the parenterally transmitted form of non-A, non-B hepatitis (NANBH). The anti-HCV test is reactive in the majority of cases with chronic NANBH. However, seroconversion is delayed by weeks or even months and therefore the test is inappropriate for confirmation of acute NANBH. Most patients with autoimmune hepatitis and some with alcoholic liver injury were shown to be anti-HCV reactive, giving rise to a debate on the specificity of the anti-HCV test. The significance of these findings has not yet been explained, since a confirmation test is currently lacking. Alpha-interferon has been shown to be the first promising drug for treatment of chronic viral hepatitis. In a high percentage of patients with chronic NANBH, treatment with interferon induces biochemical and histological remission. Nevertheless, about half of the patients had relapses under the treatment regimens currently used. The aim of ongoing studies is to improve results by optimizing the dosage and duration of interferon treatment.

Blood Donors↗

[Hepatitis C antibodies in acute Non-A, Non-B hepatitis].

Stored serum samples of 20 patients with clinically and bioptically proven non-A, non-B hepatitis (NANBH) in the acute stage were tested for the presence of antibodies to hepatitis C virus (anti-HCV) by means of the Ortho ELISA system. After a mean period of 8 weeks from onset of the disease, 8 of 20 patients (40%) had anti-HCV. Our follow-up study included 14 patients. Of 9 primarily anti-HCV-negative patients, 2 became positive after 2 and 7 months respectively, whereas 7 patients remained anti-HCV-negative up to 52 months (range 1-128) after the onset of hepatitis. The prevalence of anti-HCV was 71% in 7 patients with parenteral hepatitis related to transfusions (n = 2) or drug abuse (n = 5), and 38% in 13 patients with sporadic NANBH. Of the 8 anti-HCV-negative patients with sporadic NANBH, 5 had stayed in one of the countries where enterically transmitted NANBH is endemic 3 to 6 weeks before the onset of their disease. Our results show that at present the anti-HCV-test supplies an etiologic basis for approximately half of all cases of NANBH in acute stage. Nevertheless, in most cases the acute NANBH remains a diagnosis of exclusion.

Adolescent↗

Limited proteolysis of lactate dehydrogenase from porcine heart with trypsin: characterization and reactivation of the fragments.

The ternary complex formed by native lactate dehydrogenase (LDH) from porcine heart, NAD+ and sulfite, was digested with trypsin over a period of 12-16 h3. After removal of the ligands and residual native lactate dehydrogenase by ion exchange chromatography dimers were obtained which were almost inactive. The dimers were lacking a hexapeptide at the N-terminus; however, the secondary structure was the same as that of native lactate dehydrogenase. The circular dichroism spectra showed a dependence on temperature which suggested an equilibrium of two different structural states. The reaction of antibodies against native porcine heart LDH with the dimers restored the catalytic activity, and subsequently the dimers behaved similarly to the native enzyme. Addition of 1 M phosphate or NAD-sulfite to the dimers restored 80-90% of the catalytic activity. It could be demonstrated that the behavior of the reactivated dimers, in contrast to that of the inactive dimers, was similar to the behavior of native lactate dehydrogenase. For instance, ultracentrifugal analysis showed that dimers reactivated with NAD-SO3- were associated to give tetramers. The reaction of antibodies against native LDH with the dimers reactivated with NAD-SO3- demonstrated that the native LDH and the dimers have the same surface determinants.

Amino Acid Sequence↗