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Biomedical subjects

L Theilmann

Publications and source records attributed to L Theilmann.

At least 37 records · Page 2Linked to original sources
PubMed1997

MRI findings in chronic hepatic encephalopathy depend on portosystemic shunt: results of a controlled prospective clinical investigation.

BACKGROUND/AIMS: Deterioration of hepatic encephalopathy is a major concern with the transjugular intrahepatic portosystemic shunt procedure. Symmetric hyperintense globus pallidus on T1-weighted cranial magnetic resonance imaging in patients with liver cirrhosis anticipates hepatocerebral disease. It is hypothesized that hepatic encephalopathy and basal ganglia signal intensity progress in patients with cirrhosis of the liver undergoing transjugular intrahepatic portosystemic shunt. METHODS: Twenty-four patients were randomized to undergo either transjugular intrahepatic portosystemic shunt or elective sclerotherapy. At study entry and 6 months after randomization, neurologic assessment, psychometric tests, standard EEG, and magnetic resonance imaging were performed. The severity of liver failure was graded using Child-Pugh's classification. The signal intensity of the globus pallidus was determined on sagittal T1-weighted magnetic resonance imaging. RESULTS: The T1-weighted signal intensity of the globus pallidus on magnetic resonance imaging significantly increased after transjugular intrahepatic portosystemic shunt placement (p<0.01), but not with elective sclerotherapy. At follow-up, neurological symptoms indicating decline of mental status and motor performance were somewhat more prevalent in transjugular intrahepatic portosystemic shunt patients. Significant deterioration of EEG abnormalities occurred in patients treated with transjugular intrahepatic portosystemic shunt as opposed to elective sclerotherapy (p<0.01). CONCLUSIONS: Transjugular intrahepatic portosystemic shunt procedure increases hyperresonant globus pallidus on magnetic resonance imaging. Neuropsychiatric evaluation shows advancing hepatic encephalopathy, in particular with transjugular intrahepatic portosystemic shunt; however, it does not parallel the augmentation of pallidal signal intensity on magnetic resonance imaging.

Adult↗
PubMed1997

Clinical presentation of GB-C virus infection in drug abusers with chronic hepatitis C.

BACKGROUND/AIMS: Recently, the hepatitis GB-C virus (GBV-C) has been identified as another virus potentially causing chronic hepatitis. Although high rates of coinfection are emerging in drug addicts with chronic hepatitis C virus infection, no detailed data on clinical presentation are available. Therefore, co-infection was sought in hepatitis C virus patients to determine the impact of GB-C virus on clinical presentation. METHODS: GBV-C was determined by nested reverse transcriptase-polymerase chain reaction in serum of 70 HIV negative intravenous drug abusers with chronic hepatitis C. Biochemical, histological and virological parameters were compared between patients with or without GBV-C coinfection. RESULTS: Hepatitis C virus and GBV-C coinfection was found in 18 of 70 (25.7%) patients. Cases with coinfection were younger and had shorter duration of disease (31.4+/-6.2 vs. 35.3+/-7.3 (p=0.09) and 9.9+/-6.8 vs. 12.9+/-7.7 (p=0.17) years) than those without coinfection. Neither hepatitis C virus genotype distribution and HCV RNA levels nor serum liver function tests, titers of immunoglobulins or autoantibodies differed between the two groups. Histologically, chronic active hepatitis (16.7 vs. 46.4%, p=0.07), fibrosis (8.3% vs. 21.4%, p=0.3), and cirrhosis (0% vs. 8.2%, p=0.31) were less prevalent in coinfected patients. After interferon treatment, 5/6 coinfected and 11/19 patients with hepatitis C virus infection alone had cleared HCV RNA and 4/6 lost GBV-C RNA from serum. The two patients with GBV-C/HCV infection who persistently cleared hepatitis C virus but not GBV-C from serum had normal transaminases during follow-up despite persistence of GBV-C. CONCLUSIONS: Coinfection of chronic hepatitis C patients with GBV-C does not lead to a significant change in clinical presentation, severity of liver disease, hepatitis C viremia, or response to interferon treatment.

Adult↗
PubMed1997

Efficacy of ursodeoxycholic acid treatment and endoscopic dilation of major duct stenoses in primary sclerosing cholangitis. An 8-year prospective study.

BACKGROUND/AIMS: Primary sclerosing cholangitis is characterized by progressive fibrotic inflammation and obliteration of intra- and extrahepatic bile ducts. Ursodeoxycholic acid treatment leads to improvement of biochemical parameters of cholestasis and in part also of liver histology. During treatment, obstruction of major ducts may lead to deterioration of liver function, which may be prevented by endoscopic dilation of the stenoses. Controlled trials for evaluation of the beneficial effects of ursodeoxycholic acid treatment and of endoscopic measures in patients with major duct stenoses have become clinically difficult. Estimation of survival probabilities without treatment allows comparison of actuarial survival with the estimated survival probabilities. METHODS/RESULTS: We studied survival in 65 patients with PSC treated with ursodeoxycholic acid (750 mg/day) and by endoscopic measures whenever necessary. Patients with decompensated cirrhosis in whom transplantation was foreseen were excluded. The study was started in May 1987 and the mean follow-up period was 45.0+/-3.5 (mean+/-SEM) months. Liver histology was performed in each of the patients before entry into the study and revealed that 21% were in stage 1, 37% in stage 2, 21% in stage 3 and 20% in stage 4. Of 65 patients, 12 had major duct stenosis at entry and another 11 developed major duct stenosis during ursodeoxycholic acid treatment, which was successfully treated by repeated endoscopic balloon dilations. The actuarial Kaplan-Meier survival probabilities without liver transplantation after treatment with ursodeoxycholic acid and dilation of major duct stenoses were significantly improved compared to the predicted survival rates with p=0.001. CONCLUSIONS: Ursodeoxycholic acid does not prevent major bile duct occlusion. When ursodeoxycholic acid treatment and endoscopic opening of duct stenoses are combined, survival may be significantly improved.

Adolescent↗
PubMed1997

Transjugular intrahepatic portosystemic stent shunt versus sclerotherapy plus propranolol for variceal rebleeding.

BACKGROUND & AIMS: In patients with cirrhosis of the liver, after the first variceal bleeding episode, transjugular intrahepatic portosystemic stent shunting (TIPS) and endoscopic sclerotherapy plus propranolol (ES) were compared regarding prevention of variceal rebleeding and mortality. METHODS: Eighty-three patients with cirrhosis of the liver were randomized to undergo TIPS (n = 42) or ES (n = 41). RESULTS: Median observation time was in 1.6 years in the TIPS group and 1.45 years in the ES group. Cumulative rates of rebleeding were 23% in the TIPS group and 57% in the ES group (P = 0.0001). Hepatic encephalopathy was observed in 29% of the patients in the TIPS group and in 13% of those in the ES group (P = 0.041). Cumulative rates of survival were 69% in the TIPS group and 67% in the ES group (P = 0.62). Mortality rates in both groups were positively correlated with a higher Child's classification. CONCLUSIONS: Although TIPS significantly reduced the rate of rebleeding, survival rates were not improved. Because TIPS is associated with an increased risk of encephalopathy and high rates of shunt dysfunction, which requires reintervention, the procedure cannot be recommended for elective treatment after the first variceal bleeding episode, but it is an effective therapy in patients in whom endoscopic sclerotherapy fails to control bleeding.

Adult↗
PubMed1997

Establishment of persistent hepatitis C virus infection and replication in vitro.

Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis. Development of anti-viral strategies has been hampered by the lack of efficient cell systems to propagate HCV in vitro. To establish a long-term culture system, we tested human hepatoma (HuH7, HepG2) and porcine non-hepatoma (PK15, STE) cell lines, as well as several culture and infection conditions. As a marker for virus replication, minus-strand HCV RNA in infected cells was detected by an enhanced detection system using nested RT-PCR followed by hybridization analysis. Short-term efficiency of HCV infection (10 days) was slightly increased by addition of polyethylene glycol (PEG) and/or dimethyl sulfoxide (DMSO) to culture media during inoculation of HuH7, PK15 and STE cells, but no augmentation in long-term culture was achieved, suggesting enhanced attachment of HCV to cells rather than more efficient infection. A stabilizing effect on HCV propagation was observed for 50 days in a serum-free medium with stimulation of the low-density lipoprotein (LDL) receptor expression by lovastatin. Using partially serum-free culture conditions, long-term persistence of HCV in cells and release of virions into supernatant was achieved for up to 130 days. Infectivity of released virions in supernatants after long-term culturing (day 30-80) was shown by successful infection of fresh cells. In conclusion, supplementation with PEG, DMSO and lovastatin during inoculation did not enhance virus replication substantially, but continued stimulation of LDL-receptor expression resulted in infections which persisted for over 4 months. These data support the hypothesis of an LDL-receptor mediated uptake of HCV into cells in vitro.

Aged↗
PubMed1997

Analysis of hepatitis C virus core protein interaction domains.

Hepatitis C virus (HCV) core protein forms the internal viral coat that encapsidates the genomic RNA and is enveloped in a host cell-derived lipid membrane. As the single capsid protein, core should be capable of multimerization but attempts to produce virus-like particles following expression of HCV structural proteins have not been successful. In this study, we have analysed the interaction capacity of full-length and truncated HCV core using the yeast two-hybrid system. Full-length core containing or lacking the translocation signal for the E1 glycoprotein did not interact with full-length or truncated core proteins. Truncation to the N-terminal 122 aa revealed an interaction domain which was mapped to the tryptophan-rich sequence from aa 82-102 and was termed the main homotypic interaction domain. The C-terminal hydrophobic fragment of core (aa 122-172) was incapable of interacting with itself but interacted with the main homotypic interaction domain in trans (the weak heterotypic interaction domain). Core proteins truncated at their N and C termini (aa 46-102) were trans-activating when fused to the DNA-binding domain of GAL4. Based on our results, we suggest that the C-terminal segment may interact in cis with the main homotypic interaction domain and thereby prevent multimerization. Core-core interaction was also observed for in vitro-translated proteins bound to truncated immobilized core 102. However, interaction was less specific in this system suggesting that protein interaction and possibly conformational alteration of core may be dependent on the experimental system.

Hepacivirus↗
PubMed1997

Fatal hepatic necrosis after isoflurane anaesthesia.

Several halogenated anaesthetic agents have been associated with hepatotoxicity. We report a case of fulminant, fatal hepatic necrosis after uneventful isoflurane anaesthesia in a patient without previous liver disease, who may have been sensitised by previous exposure to enflurane. Although no anti-trifluoroacetyl antibodies could be detected in the patient's serum, isoflurane hepatotoxicity seems very likely to be the reason for fulminant hepatic failure in this patient.

Adult↗
PubMed1997

Risk of infection with Helicobacter pylori and hepatitis A virus in different groups of hospital workers.

OBJECTIVES: The purpose of this study was to determine whether different staff groups in an acute care hospital are at increased risk of acquiring Helicobacter pylori and hepatitis A virus infection. METHODS: We examined staff members of an acute care hospital for serum antibodies to H. pylori IgG (n = 457) and to hepatitis A virus (n = 434). The staff members were assigned to three groups: 1) nonmedical staff (n = 110), 2) medical and nursing staff (n = 272), and 3) medical and nursing staff working in a gastroenterology and endoscopy unit (n = 75). Serum antibodies were measured by validated enzyme immunoassays. A questionnaire inquiring about medical and professional history, history of upper GI pain and ulcer, as well as about the use of nonsteroidal anti-inflammatory drugs or medication for GI complaints and smoking habits was completed by each person. RESULTS: The seroprevalence of H. pylori was 35.5% in group I, 34.6% in group II, and 24.0% in group III (not significant). The seroprevalence of H. pylori antibodies increased with age (p < 0.001), and antibodies were present more frequently in women than in men (36.2 vs 25.4%, p < 0.05). After adjustment for age, duration of experience and the number of years working in the gastroenterology or endoscopy unit did not increase H. pylori seropositivity. No significant association was found between H. pylori seropositivity and history of upper GI pain, ulcers, use of nonsteroidal anti-inflammatory drugs or medication for GI complaints, or tobacco use. The prevalence of hepatitis A antibodies was similar in the three groups (group I, 26.4%; II, 26.5% III, 21.7%; not significant). Cross-tabulation showed that 67 subjects (15.4%) were seropositive for both H. pylori and hepatitis A (p < 0.001) and that 245 (56.5%) were negative for both. Seventy-seven (17.7.%) and 45 (10.4%) were seropositive for only H. pylori and for only hepatitis A, respectively. CONCLUSION: Occupational exposure to patients in an acute care hospital as well as to patients and to endoscopic procedures of a gastroenterology and endoscopy unit does not increase the rate of infection with H. pylori. The significant correlation between the seroprevalences of H. pylori and hepatitis A antibodies suggests fecal-oral transmission of H. pylori.

Adolescent↗
PubMed1997

Recurrent hepatitis C virus infection after liver transplantation--long-term follow-up with respect to the HCV genotypes/subtypes.

BACKGROUND/AIMS: Various factors may affect the postoperative course in recurrent hepatitis C virus (HCV) infection after liver transplantation (OLT). The aim of our study was to evaluate the potential role of HCV genotypes and immunosuppressive treatment. METHODS: 17 liver allograft recipients, HCV-RNA positive prior to OLT, were followed 26-102 months postoperatively. The diagnosis of HCV infection was based on clinical, serological and histological findings and detectable HCV-RNA in serum. The genotypes/subtypes were evaluated by a "reverse line probe" assay. RESULTS: After OLT hepatitis C viremia was evident in 16 of 17 allograft recipients (94%). Two patients acquired HCV infection after transplantation (incidence 0.84%). Clinically eight of 18 viremic patients remained asymptomatic. Ten of 18 had an acute hepatitis (eleven to 27 weeks after OLT), of those nine patients developed chronic hepatitis (hepatic activity indices: grade 1-3) with progression to fibrosis in two patients. One patient subsequently developed cirrhosis. Subtype 1 b was predominant (eleven of 18 patients). After transplantation subtype 1 b was not associated with a higher rate of recurrent hepatitis compared to other genotypes/subtypes (45% in type 1 b vs. 71% in type "non-1 b"; n.s.). CONCLUSION: Identical HCV genotypes/subtypes before and after OLT indicate a recurrent rather than a postoperatively acquired HCV infection of the allograft. Despite viremia most patients had no or mild to moderate hepatitis in the long-term follow-up. Different HCV genotypes were not associated with specific clinical courses of recurrent HCV infection after OLT.

Adolescent↗
PubMed1997

Prevalence of serum antibodies to Helicobacter pylori and to CagA protein in liver transplant recipients.

OBJECTIVE: To study Helicobacter pylori seroepidemiology before and after orthotopic liver transplantation. METHODS: Serum samples obtained from 118 liver transplant recipients before and after transplantation were examined for the presence of IgG antibodies to H. pylori whole cell extract and to the CagA protein of H. pylori. RESULTS: Of 118 patients, 64 (54.2%) were H. pylori positive, and 36 (56.3%) of these had CagA antibodies. Of the 64 seropositive patients, 22 (34.4%) remained positive and 42 (65.6%) became negative for H. pylori antibodies a median of 39 months after transplantation. Patients who seroreverted showed a tendency to lower pretransplantation antibody levels and had received antibiotic therapy for at least 4 days. Seroreversion or antibody persistence was not affected by age, sex, CagA antibody status, CagA antibody titer, duration of antibiotic therapy, or immunosuppressive drugs administered after liver transplantation. CONCLUSIONS: The prevalence of H. pylori infection, as detected by serological screening, in patients selected for liver transplantation is not different from that in the general population. In these patients, the seroprevalence of H. pylori drops after liver transplantation. This is largely due to the intake of antibiotics and immunosuppressants by transplant recipients. Seroreversion seems to be independent of the type of H. pylori bacteria.

Adult↗
PubMed1997

[Rehabilitation of patients with alcoholic liver cirrhosis after orthotopic liver transplantation: a 7-year follow-up].

Alcoholic liver cirrhosis is the main indication for orthotopic liver transplantation. Since 1988, 52 patients with alcoholic liver cirrhosis have been transplanted at the Department of Surgery of the University of Heidelberg. The survival rates are as follows: 73% of the patients survived for 1 year, 68% for 2 and 3 years, 64% for 4 years, and 57% survived for 5 years. After transplantation, recidivism occurred in 6 patients. Remarkable in this case was the fact that all 6 patients had a relatively short period of abstention prior to surgery (2 to 5 months). In 12 patients, a small carcinoma was found in the cirrhotic liver. This had neither been seen previously by ultrasound nor by computer tomography. In summary, orthotopic liver transplantation is an excellent mode of treatment in end-stage alcoholic liver cirrhosis. However, the patients have to be carefully selected in order to avoid recidivism following transplantation.

Adult↗
PubMed1997

[Prevention of hepatitis B--analysis of cost-effectiveness after liver transplantation].

HBV recurrence, despite immunoprophylaxis which occurred in 67% of our patients, remains the main problem following liver transplantation for HBV infection. Pretransplant viral replication (HBV-DNA) and probably viral mutation may account to some degree for the failures involved in hyperimmunoglobulin prophylaxis. In order to improve the cost/benefit relationship, only HBV-DNA and HBeAG-negative patients should be selected or preoperatively seroconverted by nucleosides (famciclovir, lamivudine); post-operatively a variable HIG prophylaxis should be administered.

2-Aminopurine↗
PubMed1996

Hepatitis B virus nucleic acids associated with human peripheral blood mononuclear cells do not originate from replicating virus.

There have been numerous reports suggesting that human peripheral blood mononuclear cells (PBMCs) can be productively infected with human hepatitis B virus (HBV). We therefore examined whether the PBMCs can be used to establish an in vitro infection system for HBV. Freshly purified PBMCs were incubated with HBV with or without mitogen stimulation. Successful infection was tested using a newly developed PCR method that can differentiate between the relaxed circular (RC) DNA of the virus inoculum and the covalently closed circular (CCC) DNA which is formed only after successful virus entry. This method enables virus uptake to be proven even if the infection is abortive because there is no gene expression because of the lack of liver specific gene expression factors. All attempts to detect CCC DNA after incubation of PBMCs with HBV failed. On the contrary, CCC DNA could easily be detected in infected liver or after in vitro infection of primary human hepatocytes. Because this result appeared to be contradictory to the published data, we analyzed PMBCs isolated from infected patients. We could confirm that HBV DNA and RNA are associated with these cells. However, even after restimulation with mitogens, we could only detect RC DNA. Moreover, we could also demonstrate that viral RNA is present in free virus. Apparently, a certain amount of defective particles do not reverse transcribe the packaged pregenomic RNA. In summary we found no evidence that PMBCs can be infected with HBV and conclude that all previous observations can be explained by adsorbed virus.

Base Sequence↗
PubMed1996

Phenprocoumon for prevention of shunt occlusion after transjugular intrahepatic portosystemic stent shunt: a randomized trial.

Development of stenosis or occlusion of the transjugular intrahepatic portosystemic stent shunt (TIPSS) is one of the major limiting factors in the long-term viability of this procedure. The efficacy of anticoagulation with heparin which is used in different centers is still unclear. In the present study, we evaluated the effect of phenprocoumon on shunt patency after TIPSS placement using Palmaz stents; 49 patients with Child's A and B cirrhosis, who underwent successful TIPSS placement were randomized into the treatment group (n = 24) who received phenprocoumon and a control group (n = 25). After 11 to 13 weeks, all patients were admitted and had a reevaluation that included control angiography by transjugular approach. Phenprocoumon treatment was stopped after the first reevaluation and both groups were followed for 1 year after randomization. During the 3-month treatment period 11 of 22 patients of the treatment group and 12 of 23 patients of the control group required reintervention because of an increased portosystemic gradient. Five of the 12 patients in the control group showed complete occlusion of the shunt, whereas no occlusion in the treatment group was observed (P < .05). During the mean follow-up of 8 months after the treatment was stopped, in both groups stenosis occurred in 50% of patients, but no further occlusion of the stent was observed. These data indicate that occlusion of the stent is related to thrombosis, whereas stenosis does not appear to be dependent on blood coagulation. In patients with preserved liver function occlusion of the shunt may be prevented by phenprocoumon treatment in the first 3 months after TIPSS placement. Thereafter shunt occlusion was not observed and further phenprocoumon treatment seemed unnecessary.

Anticoagulants↗
PubMed1996

Sequence analysis of hepatitis GB virus C (GBV-C) isolates from 14 patients.

In 1995, a new human hepatitis virus belonging to the family Flaviviridae was described and designated hepatitis GBV-C. To investigate variations within the genome of GBV-C and to study the relationship of GBV-C to GBV-A/B or hepatitis C virus (HCV), we established a detection system using reverse transcriptase polymerase chain reaction (RT-PCR) of the putative helicase region (NS3). So far, isolates derived from 14 different GBV-C-positive sera were analyzed (GBV-C/S3-36), showing 80.1-89.4% (mean: 85%) identical nucleotides. The deduced amino acid sequences revealed 97.3% homology. Nucleotide sequences of GBV-C/S3-36 revealed about 60% identity to GBV-A as well as to HCV, but only 56% identity to GBV-B. Amino acid sequences revealed 73.4 and 68.6% similarity to GBV-A and GBV-B, respectively, but a slightly higher percentage of 78.5% to HCV sequences. Thus, according to the putative GBV-C helicase sequence, a subtyping of GBV-C into different genotypes may be necessary.

Adult↗
PubMed1996

Kinetics of primary bile acids in patients after orthotopic liver transplantation.

Administration of cyclosporin A (CsA) may induce cholestasis, and this effect has been attributed to impaired hepatocellular uptake, transport, secretion and intestinal absorption of bile acids. Disturbances of the enterohepatic circulation may affect metabolism of bile acids. To test whether liver transplantation and treatment with CsA alters pool sizes or synthesis and turnover rates, we determined kinetics of primary bile acids in patients after orthotopic liver transplantation on CsA. Two male and four female patients were studied 6-20 months after transplantation. They had no overt signs of cholestasis, graft dysfunction or rejection. Kinetics of cholic acid (CA) and chenodeoxycholic acid (CDCA) were simultaneously determined after oral administration of [24-13C]-CA and [24-13C]-CDCA on the basis of isotope dilution in a single pool of bile acids. Ten healthy volunteers served as controls. After orthotopic liver transplantation, pool sizes, fractional turnover rates and synthesis rates of both primary bile acids, CA and CDCA were not significantly different from control subjects. In spite of the known interference of CsA with the enterohepatic circulation of bile acids, in the majority of patients after orthotopic liver transplantation without cholestasis, graft dysfunction of rejection, treatment with CsA does not disturb kinetics of primary bile acids.

Adult↗