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Biomedical subjects

L Theilmann

Publications and source records attributed to L Theilmann.

At least 55 records · Page 3Linked to original sources
PubMed1996

Neuropsychiatric profile and hyperintense globus pallidus on T1-weighted magnetic resonance images in liver cirrhosis.

BACKGROUND & AIMS: Hyperintense globus pallidus on T1-weighted magnetic resonance images (MRIs) in cirrhotic patients are reported to reflect severity of liver disease; however, their consequence for hepatic encephalopathy is unknown. The aim of this study was to outline a pattern of neuropsychiatric abnormalities in chronic liver failure and its correlation with MRI findings. METHODS: Fifty-one consecutive patients were enrolled in the study. Neuropsychiatric assessment used a standardized protocol, including dichotomized neurological parameters, brief psychiatric rating and psychometric tests, as well as electroencephalography. The severity of liver failure was graded using standard laboratory parameters and the Child-Pugh's classification. Signal intensity of the globus pallidus was determined on sagittal T1-weighted MRIs. RESULTS: Two aspects of neurological dysfunction could be distinguished by principal components analysis: impairment of complex cerebral function and subcortical motor performance. Both neurological categories correlated with severity of liver failure, grade of electroencephalographic abnormalities, and psychometric test results. Additionally, prior bouts of overt encephalopathy indicate progressive dementia. T1-weighted globus pallidus signal intensity did not correlate with any clinical or laboratory test result. CONCLUSIONS: This study shows a characteristic pattern of neurological findings in patients with liver failure and hyperintense globus pallidus on T1-weighted MRIs. Although neurological dysfunction parallels hepatic failure, MRI abnormalities of basal ganglia do not indicate severity of actual hepatic encephalopathy.

Adolescent↗
PubMed1996

A novel two-nucleotide deletion in the ornithine transcarbamylase gene causing fatal hyperammonia in early pregnancy.

Ornithine transcarbamylase (OTC) deficiency shows X-linked inheritance. Typically, symptomatic females (who constitute 15%-20% of all carriers) have markedly reduced enzyme activity and show first symptoms in late infancy or early childhood. Here we present the case of a previously asymptomatic 24-year-old woman who died of severe hyperammonemia associated with orotic aciduria but normal OTC activity in the fourth month of pregnancy. DNA analysis revealed a novel mutation in form of the deletion of two nucleotides (T892, G893) in exon 9 of the OTC gene, leading to a frame shift and an aberrant gene product. We suggest that OTC deficiency should be suspected in any patient who presents with hyperammonia in the presence of otherwise normal liver function.

Adult↗
PubMed1996

Low prevalence of alterations in the pancreatic duct system in patients with primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is a rare disease of unknown origin that involves the intrahepatic or extrahepatic biliary system, or both. To obtain more precise information on concomitant involvement of the pancreatic duct system, a comparatively large group of 44 patients was studied. PATIENTS AND METHODS: Between 1989 and 1995, 44 patients took part in a study of the therapeutic effect of ursodeoxycholic acid, and their data were analyzed. In 42 of the 44 patients, both the pancreatic and biliary system were visualized by endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Pancreas divisum was detected in four patients (9.5%) with an otherwise normal major pancreatic duct. Three (7.1%) patients had pancreatic duct changes of the type seen in chronic pancreatitis. When risk factors such as alcohol abuse were excluded, there was only one patient with PSC and pancreatic duct alterations. CONCLUSION: In PSC patients, the prevalence of chronic pancreatitis is low.

Adult↗
PubMed1996

Immunogenicity and reactogenicity of a combined hepatitis A/B candidate vaccine: first results.

We evaluated immunogenicity and reactogenicity of an inactivated, combined hepatitis A/B candidate vaccine in 50 seronegative volunteers. Each volunteer received a total of three doses of vaccine (720 EIU HAV and 20 micrograms HBs antigen) according to a 0, 1 and 6 month vaccination schedule. One month after the first injection, the seroconversion rate was 90% (45/50) for anti-HAV and 28% (14/50) for anti-HBs, respectively. After the booster dose, at month 7, the seroconversion rate was as high as 100% (49/49) for anti-HAV and 94% (46/49) for anti-HBs. The geometric mean titres increased with each dose of vaccine administered. Mild, and mostly local side effects were reported in 54% of the volunteers after the first injection and in less than 10% after the third injection. Our results show that this inactivated, candidate hepatitis A/B vaccine is highly immunogenic and well-tolerated.

Adult↗
PubMed1995

[Immunogenicity and tolerance of a combined hepatitis A/B vaccine. Preliminary results with a candidate vaccine].

AIM OF STUDY: Active immunization against hepatitis A having been undertaken in Germany since January 1993, a multicentre study was conducted to test, for the first time, immunogenicity of and tolerance to a candidate vaccine against hepatitis A and B. SUBJECTS AND METHODS: 50 healthy volunteers aged 18-40 years, negative for antibodies against hepatitis A (HAV) and B (HBs), received three intramuscular injections of the candidate vaccine (720 EIU of strain HM 175 and 20 micrograms recombinant HBsAg) in a total volume of 1 ml, on day 1 and then, one month and 6 months later. RESULTS: Four weeks after the first injection the seroprotection rate (percentage of subjects with protective antibody titres) was 90% for HAV and 28% for HBs. The second injection produced seroconversion rates of 98% and 50%, respectively, and after the third one of 100% and 98%. All reported side effects were minor, of short duration and decreased after each injection. After the first injection, effects at the site of injection occurred in 50% of subjects, decreasing to 6% after the third one. The only systemic side effect, headache, occurred in only 4% of subjects and only after the first injection. CONCLUSION: The test vaccine against hepatitis A and B proved to be highly immunogenic, safe and well tolerated.

Adolescent↗
PubMed1995

[Acute liver failure as the initial manifestation of Wilson disease].

BACKGROUND: Establishing an early diagnosis is crucial to successfully treat mostly young patients with sudden onset acute hepatic failure as the initial symptom of Wilson's disease. Recognition of the entity of Wilsonian fulminant hepatitis is important, because liver transplantation improves survival if performed in a timely fashion. METHODS: Retrospective case analysis regarding characteristic profile of standard laboratory parameters and clinical course of acute Wilsonian hepatic failure. RESULTS: In two female patients (age 17 and 27 years) with non-autoimmune hemolysis serum AST and ALT levels were only moderately elevated with a conspicuously diminished ALT activity and relatively low serum alkaline phosphatase (AP) levels. Despite immediate application of D-Penicillamin one patient died from complications of multiorgan failure. CONCLUSION: In fulminant Wilsonian hepatic failure the AP/bilirubin ratio is usually below 2. Additionally calculation of free copper concentration in serum and renal excretion of ionic copper in combination with non-autoimmune hemolysis provide clues to establish an early diagnosis of Wilsonian hepatic failure.

Adolescent↗
PubMed1995

[Significance of genotypes in chronic hepatitis C virus infection and hepatitis C virus induced liver cirrhosis in Germany].

INTRODUCTION AND OBJECTIVE: Hepatitis C virus (HCV) infection is characterized by a high chronicity rate. Several HCV genotypes have been described. As their distribution pattern in Germany had been unknown it was the aim of this study to determine it in a sizeable group of patients and to find out whether the genotypes differ in the severity of the disease caused by them. PATIENTS AND METHODS: 115 consecutive patients were studied prospectively, 62 (40 men, 22 women) with chronic HCV infection (group 1) and 53 (36 men, 17 women) with liver cirrhosis caused by HCV (group 2). The genotypes were determined by line probe assay. RESULTS: The mean age of the patients in group 1 was significantly lower than that in group 2 (40.4 +/- 13.7 vs 57.1 +/- 12.1 years; P < 0.0001). In group 1, genotype 1b was most frequent (53%; 1a: 21%, 3a: 21%, 2b: 3%, 2a: 2%). Genotype 1b also predominated in group 2 (78%; 1a: 17%, 2a: 4%, 3a: 2%). The differences in frequency between the two groups were significant regarding genotypes 1b (P = 0.01) and 3a (P = 0.005). Genotype 3a was found only in the younger patients. Mean age of patients with genotype 3a and chronic hepatitis C was significantly lower than that of the other patients in this group (34.2 +/- 4.6 vs 42.0 +/- 14.8 years; P < 0.002). CONCLUSIONS: The results show that in Germany genotype 1b predominates and seems to be associated more often with the advanced stages of liver disease. The fact that genotype 3a occurs exclusively in younger patients points to a change in genotype spectrum: infection with this genotype may take a less aggressive course since fewer cases of liver cirrhosis have been observed.

Adult↗
PubMed1995

Manganese and chronic hepatic encephalopathy.

Clinical observations and animal studies have raised the hypothesis that increased concentrations of manganese (Mn) in whole blood might lead to accumulation of this metal within the basal ganglia in patients with end-stage liver disease. We studied ten patients with liver failure (and ten controls) by magnetic resonance imaging (MRI) and measurement of Mn in brain tissue of three patients who died of progressive liver failure (and three controls) was also done. Whole blood Mn concentrations in patients with liver cirrhosis were significantly increased (median 34.4 micrograms/L vs 10.3 micrograms/L in controls; p = 0.0004) and pallidal signal intensity indices correlated with blood Mn (Rs = 0.8, p = 0.0058). Brain tissue samples reveal highest Mn concentrations in the caudate nucleus, followed by the quadrigeminal plate and globus pallidus. Mn accumulates within the basal ganglia in liver cirrhosis. Similarities between Mn neurotoxicity and chronic hepatic encephalopathy suggest that this metal may have a role in the pathogenesis of chronic hepatic encephalopathy. Further studies are warranted because the use of chelating agents could prove to be a new therapeutic option to prevent or reverse this neuropsychiatric syndrome.

Adult↗
PubMed1995

In patients with orthotopic liver transplantation, serum markers of cholestasis are unreliable indicators of biliary secretion.

BACKGROUND/AIMS: In patients after orthotopic liver transplantation, treatment with the novel immunosuppressant FK 506 may lead to elevated levels of alkaline phosphatase, gamma glutamyl transferase and bilirubin. Up to now it was unclear whether the excretory capacity of the liver in such patients is impaired. METHODS: We measured quantitatively the secretion of bile acids, phospholipids and cholesterol using the duodenal perfusion method, which allows assessment of biliary secretion without interruption of the enterohepatic circulation. Six healthy volunteers served as controls. RESULTS: All patients studied after orthotopic liver transplantation had elevated concentrations of serum alkaline phosphatase and gamma glutamyl transferase, whereas only half of them had slightly abnormal serum bilirubin levels. On average, the FK 506-treated patients excreted 1.23 +/- 0.27 mmol/h bile acids, 0.23 +/- 0.04 mmol/h phospholipids and 0.11 +/- 0.02 mmol/h cholesterol, which was not significantly different from the healthy controls. CONCLUSIONS: The normal secretion rates of biliary bile acids and lipids in FK 506-treated patients with elevated serum alkaline phosphatase and gamma glutamyl transferase indicate that the excretory capacity of the transplanted liver has completely recovered 2-3 months after surgery. In addition, in the majority of these patients elevated serum levels of alkaline phosphatase, gamma glutamyl transferase and bilirubin do not reflect impaired biliary secretion.

Adult↗
PubMed1995

[Ischemic type lesions of the bile ducts after liver transplantation: 2 years results].

Ischemic type lesions (ITL) after orthotopic liver transplantation are characterized by bile duct necroses leading to alterations of the ductal lumen, biliary leakage, cast formation and, thereby, to cholestasis. After exclusion of causative factors, such as arterial thrombosis, ABO incompatibility and chronic rejection, ITL occurred in 21 of 165 patients. The rate of ITL after UW preservation was higher (25%) in grafts preserved for > 10 hours in comparison to < 10 hours (7%; p < 0.05). Treatment consisted of endoscopic and percutaneous intervention, surgical revision and retransplantation. Retransplantation is indicated in many patients with lesions of extra- and intrahepatic bile ducts (type A). Other methods are of palliative character and may only be successful in type B (extrahepatic) lesions. Morbidity in patients with ITL is considerable. In comparison to patients without ITL, mortality, however, is not increased.

Bile Ducts↗
PubMed1995

[Portal hypertension and percutaneous transjugular portasystemic stent shunt].

This paper reports 1) the historic development of TIPSS, the transjugular intrahepatic portosystemic stent shunt from experimental evaluation to clinical realization. 2) The evolution of the instrumental technique during a period of 6 years of clinical applications is described in detail. 3) Results based on 204 consecutive procedures are demonstrated: e.g. the early technical success defined as successful completion of the procedure and 30-day survival was 95%; the clinical success defined as technically successful procedure and no rebleeding during the first 30 days was 83%, the 30-day mortality rate was 6.3%; the 30-day encephalopathy rate was 14.1%; the one-year re-bleeding rate was 11%; the one-year survival rate was 74%, the 3-year survival rate was 41%. 4) Problems of the TIPSS procedure are discussed including a 3-months re-stenosis rate of 46% and a cumulative one-year re-stenosis rate of 84% which requires correction by interventional procedures such as shunt dilatation or additional vascular stent placement. 5) Limitations and indications of TIPSS are elucidated based on hemodynamic and functional aspects of liver cirrhosis.

Esophageal and Gastric Varices↗
PubMed1995

Biliary secretion of bile acids and lipids in primary sclerosing cholangitis. Influence of cholestasis and effect of ursodeoxycholic acid treatment.

In patients with primary sclerosing cholangitis cholestasis is a prominent feature of the disease. We studied the effect of cholestasis and of ursodeoxycholic acid treatment on the biliary secretion of bile acids and lipids in ten patients with primary sclerosing cholangitis. Ursodeoxycholic acid treatment for 3 months led to an increase in the biliary secretion rates of total bile acids from 0.91 mmol/h to 1.47 mmol/h, mainly due to an increase in urosodeoxycholic acid, which represented 31% of biliary bile acids. With increasing cholestasis, the biliary enrichment of the bile acid pool with urosodeoxycholic acid decreased. Biliary output of endogenous bile acids on average was unchanged, but in patients with cholestasis and diminished output before treatment, it increased after ursodeoxycholic acid. Phospholipid secretion increased from 0.26 mmol/h to 0.43 mmol/h without correlation to the degree of cholestasis. Biliary cholesterol secretion on average was unchanged after ursodeoxycholic acid (0.1 versus 0.09 mmol/h) but, in patients with cholestasis and diminished output before treatment, it increased after ursodeoxycholic acid. The decreasing enrichment of the bile acid pool with ursodeoxycholic acid with increasing cholestasis may be related to its slight effect in advanced disease. The increase in biliary phospholipid secretion may represent another mechanism of action of urosodeoxycholic acid responsible for its beneficial effect in cholestatic liver disease.

Adolescent↗
PubMed1994

Characterization of antigenic determinants in the core antigen of the hepatitis C virus.

Antibodies to the hepatitis C virus (HCV) core protein are present in the majority of patients with chronic HCV infection. To characterize the corresponding determinants, synthetic peptides and various deletion clones of the core gene expressed in Escherichia coli were used to test human anti-core positive sera or rabbit anti-peptide antibodies in enzyme-linked immunosorbent assays, immunoblots, and competition assays. Two distinct linear antigenic determinants which are located within aa 1 to 20 and between aa 30 and 47 were found. Further studies using reactive serum after preabsorption of antibodies with N- and C-terminal-deleted HCV core proteins or with peptides directed to the linear epitopes revealed an additional determinant that requires for presentation the participation of the N-terminal 69 amino acids. It is postulated that the HCV core protein forms a three-dimensional structure exposing two linear epitopes and, in addition, presents a conformational determinant within the N-terminal 69 amino acids. The remaining core amino acid sequence spanning from position 69 to 191 does not seem to expose further determinants to induce additional anti-core antibodies.

Animals↗
PubMed1994

B-lymphocytes are predominantly involved in viral propagation of hepatitis C virus (HCV).

Recent reports have shown that HCV infection is not only restricted to hepatocytes. Like hepatitis B virus (HBV), which also was thought to be strictly hepatotropic in early molecular and cellular investigations, infection of lymphoid cells by HCV in vivo has been demonstrated. We showed that total peripheral blood leukocytes of chronically HCV-infected patients are infected by detection of plus- and minus-stranded HCV RNA using strand-specific oligonucleotide primers in the RT-PCR. These cells also represent extrahepatic sites for the viral replication, as demonstrated by incorporation of [3H]-uridine into nascent RNA after stimulation of the cells with a mitogen. Furthermore, total PBML from an uninfected person could be infected in vitro using an HCV-positive serum. It could be shown that replication of HCV RNA takes place in these cells. Examination of different subsets of PBML showed predominant infection of B-lymphocytes during HCV disease. Additionally, infection of T-lymphocytes was detected in about 50% of all chronically HCV-infected patients.

B-Lymphocytes↗