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Biomedical subjects

K Berger

Publications and source records attributed to K Berger.

At least 91 records · Page 5Linked to original sources
PubMed1997

[Economic aspects of drug therapy exemplified by pravastatin. A socioeconomic analysis of cholesterol synthase enzyme inhibition in coronary heart disease patients].

BACKGROUND: Decision makers in the field of health services are increasingly forced to identify and realise the grounds for spendings and savings. Therefore, preventive measures of cardiovascular diseases are becoming more and more scrutinized. The present analysis is answering the question: Is secondary preventive lipid-lowering therapy with a cholesterol-synthesis-enzyme-(CSE-)inhibitor in patients with manifest coronary heart disease cost-effective in comparison to other already proven medical interventions? METHODS: The cost-effectiveness-analysis with the endpoint costs per life years saved had been chosen as a form of evaluation. The study is a retrospective analysis. The clinical data have been taken from the already published double blinded, randomised, placebo controlled PLAC-I- and -II-studies as well as from the PLAC-Meta-Analysis. The cost estimate (costs of myocardial infarction, stroke and cost therapy with pravastatin) were based on the perspective of the German statutory sick funds. RESULTS: With the reduced probability of a fatal myocardial infarction or a stroke in the group treated with pravastatin there are cost offsets of DM 2,400. This figure is opposed to an additional expenditure of about DM 6,900, -for the CSE-inhibitor. The calculation of the effectiveness resulted in an additional life expectancy of 0.28 years in the pravastatin cohorts in comparison with the group treated with placebo over an observation period of 3 years. The costs per life year saved are approximately DM 16,000,-. CONCLUSION: The preventive use of pravastatin in patients with coronary heart disease can be estimated as cost-effective as compared with other medical interventions.

Anticholesteremic Agents↗
PubMed1997

Hypertension and borderline isolated systolic hypertension increase risks of cardiovascular disease and mortality in male physicians.

BACKGROUND: The objective of this study was to examine whether definite hypertension and borderline isolated systolic hypertension predict subsequent cardiovascular disease and mortality. METHODS AND RESULTS: This was a prospective cohort study with a mean follow-up of 11.7 years. The subjects were a group of 18,682 apparently healthy US men, aged 40 to 84 years, participating in the Physicians' Health Study, a randomized trial of low-dose aspirin and beta-carotene. The main outcome measures were total cardiovascular disease, myocardial infarction, stroke, cardiovascular death, and all-cause mortality. Hypertension was associated with substantially increased risks of total cardiovascular disease (relative risk [RR] 1.92; 95% confidence interval [CI], 1.70 to 2.18), myocardial infarction (RR,1.78; 95% CI, 1.49 to 2.13), stroke (RR, 2.19; 95% CI, 1.78 to 2.69), and cardiovascular death (RR, 2.10; 95% CI, 1.68 to 2.63). Borderline isolated systolic hypertension was associated with significantly increased risks of cardiovascular disease (RR, 1.32; 95% CI, 1.09 to 1.59), stroke (RR, 1.42; 95% CI, 1.04 to 1.93), and cardiovascular death (RR, 1.56; 95% CI, 1.13 to 2.15), as well as a possible but non-significant increased risk of myocardial infarction (RR, 1.26; 95% CI, 0.95 to 1.67). Hypertension and borderline isolated systolic hypertension were associated with significantly increased risks of 41% and 22%, respectively, for all-cause mortality. CONCLUSIONS: Hypertension as well as borderline isolated systolic hypertension are associated with elevated risks of cardiovascular diseases, especially stroke and cardiovascular death. Hypertension is associated with an increased risk of myocardial infarction, and borderline isolated systolic hypertension predicts a possible but more modest increase in risk. These data add to the existing evidence that hypertension is a major cardiovascular risk factor and extend the findings to borderline isolated systolic hypertension.

Adult↗
PubMed1997

Hepatitis C virus core and E2 protein expression in transgenic mice.

Transgenic mice have been produced that express the hepatitis C virus (HCV) core protein in the liver under the transcriptional control of the mouse major urinary protein promoter. These animals express the full length core protein in cytoplasm of their hepatocytes at levels comparable to those detected in naturally infected patients, without histological or biochemical evidence of liver disease or hepatocellular carcinoma. This contrasts with recent reports that HCV core protein can transform NIH 3T3 cells and cooperates with H-ras to transform primary rat fibroblasts in vitro. Coexpression of HCV core protein in double transgenic mice that replicate the hepatitis B virus (HBV) does not inhibit hepatocellular HBV gene expression or replication, contrary to reports that it inhibits HBV replication in HuH-7 cells after transient transfection in vitro. We have also produced transgenic mice in which a C-terminally truncated (aa384-715) glycosylated HCV E2 protein is expressed in the liver under the transcriptional control of the mouse albumin promoter. Despite the high level expression of HCV E2 protein, no evidence of liver disease was detected in these animals. These results suggest that the HCV core and E2 proteins are not cytopathic for the hepatocyte in vivo, and they represent an initial step in the development of a small animal model of HCV immunopathology.

Animals↗
PubMed1996

[Cost effectiveness of captopril after myocardial infarct; comment].

BACKGROUND: In Germany approximately 88,000 people died as a result of acute myocardial infarction and approximately 300,000 people suffered from acute myocardial infarction in 1992. These data demonstrate the socioeconomic impact of coronary disease. In the SAVE-(Survival-and-Ventricular-Enlargement) study, Pfeffer et al. demonstrated a reduction of morbidity and mortality due to therapy with captopril in patients after myocardial infarction. In a retrospective, incremental cost-effectiveness-analysis, from the perspective of German statutory insurance fund, the economic impact of captopril after myocardial infarction has been analysed. PATIENTS AND METHOD: The basis for the economic evaluation has been the double-blind, placebo-controlled, clinical SAVE-study which included 2,231 patients having left ventricular dysfunction after acute myocardial infarction. Additional data e.g. average number of hospital days or average costs for hospitalisation per day was taken from published national statistical sources. In the cost-effectiveness-analysis, inputs (monetary units) and outputs (non-monetary units) were identified and measured. The cost-effectiveness (costs per life-year gained) demonstrates a relation between the costs of captopril-treatment, costs for myocardial infarction and costs for leftventricular insuffiency and the clinical benefit e.g. life years gained. RESULTS: Initially costs in the captopril-group are 3.7 Mio DM higher as in the placebo-group. But these costs are partly compensated by the cost reductions in the captopril-group, compared to the placebo-group (2,162,901 DM) the reduction of myocardial infarction and DM 556,518 cost reduction due to fewer patients with left ventricular dysfunction. The clinical benefit of the captopril treatment equals 495 life years gained. The cost-effectiveness-ratio is 2,000 DM cost for life year gained. CONCLUSION: The treatment with captopril after acute myocardial infarction is not only a clinically efficacious treatment, but also cost-effective in patients after acute myocardial infarction.

Adult↗
PubMed1996

[Drug-induced rhabdomyolysis and lesions of peripheral nerves. Sequelae of local ischemia within the scope of circulatory collapse?].

We report on two patients with severe rhabdomyolysis and peripheral nerve involvement after drug intoxication. Nerve conduction studies of the paretic extremities of both patients could be performed within 12 h of the onset. Several nerves revealed evidence of conduction blocks in the paretic extremities. One of the patients who had taken heroin died and postmortem examination was performed. A drug-induced immune vasculitis could not be demonstrated. Besides striated muscle necrosis, extensive myocardial fragmentation was shown. Territorial ischemia, resulting from systemic hypotension and mechanical compression of arteries, seems to have been the cause of the myonecroses and peripheral nerve damage in the unconscious patients.

Adolescent↗
PubMed1996

[Resuscitation in multiple trauma].

We report on a case of successful outpatient cardiopulmonary resuscitation of cardiac arrest after blunt multisystem injury. The literature is discussed and prognostic indicators are described.

Accidents, Traffic↗
PubMed1996

[Bleomycin-induced pneumonia].

We report on a case of a 38-year old patient with fatal bleomycin-induced pneumonitis. Clinical presentation, the impact of risk factors, therapeutic means and perioperative considerations to prevent this rare but life-threatening complication are reviewed.

Adult↗
PubMed1996

Interobserver agreement in the classification of stroke in the physicians' health study.

BACKGROUND AND PURPOSE: The evaluation of cerebrovascular end points in prospective studies is often based exclusively on medical record examination and may be made by more than one observer over time. To address the issues of adequacy of medical record information and consistency in diagnosis over time, we evaluated interobserver agreement for the main items of the stroke classification system used in the Physicians' Health Study. This trial included 22,071 physicians randomly assigned in 1982 to receive either aspirin or placebo to assess the subsequent risk of cardiovascular events, including stroke. METHODS: Stroke subtype, stroke severity, and certainty of diagnosis were first classified from medical records from the years 1982 through 1988. The 216 stroke events reported in this period were independently reclassified in 1994 and compared with the initial classification using kappa statistics. RESULTS: Overall agreement in major stroke types (hemorrhagic, ischemic, undetermined stroke) as well as in hemorrhagic stroke subtypes was excellent (kappa = 0.81 and kappa = 0.95, respectively). A wide range of values for the ischemic stroke subtypes (kappa = 0.13 to kappa = 0.96) was obtained. Agreement was substantial in assessment of stroke severity (kappa = 0.71), and it was fair (kappa = 0.33) for certainty of diagnosis. CONCLUSIONS: Interobserver agreement is high for major stroke types as well as for categories of hemorrhagic stroke on the basis of review of medical records and results of imaging data. The classification of ischemic stroke subtypes, however, is subject to substantial interobserver disagreement. Periodic reclassification of random samples of end points might be considered in long-term prospective studies to assess potential misclassification of events by different observers.

Adult↗
PubMed1996

[Determinants of patient structure according to the psychiatry personnel decree. On the problem of comparing psychiatric clinics].

In Germany psychiatric hospitals are increasingly facing external comparisons with other psychiatric hospitals and departments. The focus of these comparisons often is the constitution of inpatients according to the "Decree of Psychiatric Personnel" (Psychiatrie-Personalverordnung). This report evaluates factors that influence patient categorisation into the treatment categories of the mentioned decree. The analysis yields three sociodemographic factors as significant predictors of a categorisation to the intense-treatment category A2: 1. compulsory admission into the hospital, 2. first ever admission, 3. urban place of residence. Major methodical problems of patient categorisation into categories of the decree are elucidated. The validity of the current approach that chooses four selected qualifying days per year as the basis of representation of the annual patient population in psychiatric hospitals and departments is questioned.

Adult↗
PubMed1994

Vaccination of chimpanzees against infection by the hepatitis C virus.

A high incidence of community-acquired hepatitis C virus infection that can lead to the progressive development of chronic active hepatitis, liver cirrhosis, and primary hepatocellular carcinoma occurs throughout the world. A vaccine to control the spread of this agent that represents a major cause of chronic liver disease is therefore needed. Seven chimpanzees (Pan troglodytes) have been immunized with both putative envelope glycoproteins [E1 (gp33) and E2 (gp72)] that were copurified from HeLa cells infected with a recombinant vaccinia virus expression vector. Despite the induction of a weak humoral immune response to these viral glycoproteins in experimentally infected chimpanzees, a strong humoral immune response was obtained in all vaccines. The five highest responders showed complete protection against an i.v. challenge with homologous hepatitis C virus 1. The remaining two vaccines became infected, but both infection and disease may have been ameliorated in comparison with four similarly challenged control chimpanzees, all of which developed acute hepatitis and chronic infections. These results provide considerable encouragement for the eventual control of hepatitis C virus infection by vaccination.

Animals↗
PubMed1993

The hepatitis C virus encodes a serine protease involved in processing of the putative nonstructural proteins from the viral polyprotein precursor.

The hepatitis C virus (HCV) nonstructural protein 3 (NS3) domain has been predicted from sequence comparisons to represent a trypsin-like serine protease. By expressing wild-type and mutant HCV-1 cDNAs in transfected mammalian cells, we have identified putative nonstructural proteins 3 (72 kDa), 4 (10 kDa and 27 kDa) and 5 (58 kDa) and have shown that their processing from the viral polyprotein precursor is dependent on Ser1165 located in the proposed protease catalytic site. Data obtained from in vitro RNA translations indicate that unlike the processing of the NS2/NS3 junction, NS3/NS4 processing is dependent on Ser1165. In contrast to the situation for the related flaviviral NS3 proteases, the HCV NS3-mediated cleavage of the NS3/NS4 junction does not require the upstream NS2 domain and may not occur at dibasic sites.

Animals↗
PubMed1993

Expression, identification and subcellular localization of the proteins encoded by the hepatitis C viral genome.

We have expressed the full-length coding region and selected domains of the hepatitis C virus (HCV) cDNA in mammalian cells by transfection. Using HCV antibody-positive human sera and monospecific antibodies the proteins encoded by the putative structural and non-structural regions of the open reading frame of HCV were identified as core (p22), E1 (gp32-35), E2 (gp68-72), NS2 (p23), NS3 (p72), NS4a and b (p10 and p27) and NS5a and b (p56 and p70). We have also defined the subcellular localizations of the HCV proteins using indirect immunofluorescence assays.

Animals↗
PubMed1993

Adolescent adjustment to chronic physical disorders--I. Comparing neurological and non-neurological conditions.

Early research on child adjustment to chronic illness assumed that each condition had a unique impact. Recently researchers have suggested that all chronic conditions influence adjustment in similar ways. To compare these models, data were collected on 165 adolescents having chronic conditions with and without brain involvement, and 49 healthy controls. Adolescents with brain-based conditions had more behaviour problems, less autonomous functioning and poorer school achievement. Children with conditions having no brain involvement differed from controls only in reporting less work experience and having lower math achievement scores. These findings support a modified perspective that involves both general factors and effects specific to brain-based conditions.

Adaptation, Psychological↗
PubMed1993

Characterization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia viruses.

We constructed recombinant vaccinia virus vectors for expression of the structural region of hepatitis C virus (HCV). Infection of mammalian cells with a vector (vv/HCV1-906) encoding C-E1-E2-NS2 generated major protein species of 22 kDa (C), 33 to 35 kDa (E1), and 70 to 72 kDa (E2), as observed previously with other mammalian expression systems. The bulk of the E1 and E2 expressed by vv/HCV1-906 was found integrated into endoplasmic reticulum membranes as core-glycosylated species, suggesting that these E1 and E2 species represent intracellular forms of the HCV envelope proteins. HCV E1 and E2 formed E1-E2 complexes which were precipitated by either anti-E1 or anti-E2 serum and which sedimented at approximately 15 S on glycerol density gradients. No evidence of intermolecular disulfide bonding between E1 and E2 was detected. E1 and E2 were copurified to approximately 90% purity by mild detergent extraction followed by chromatography on Galanthus nivalus lectin-agarose and DEAE-Fractogel. Immunization of chimpanzees with purified E1-E2 generated high titers of anti-E1 and anti-E2 antibodies. Further studies, to be reported separately, demonstrated that purified E1-E2 complexes were recognized at high frequency by HCV+ human sera (D. Y. Chien, Q.-L. Choo, R. Ralston, R. Spaete, M. Tong, M. Houghton, and G. Kuo, Lancet, in press) and generated protective immunity in chimpanzees (Q.-L. Choo, G. Kuo, R. Ralston, A. Weiner, D. Chien, G. Van Nest, J. Han, K. Berger, K. Thudium, J. Kansopon, J. McFarland, A. Tabrizi, K. Ching, B. Mass, L. B. Cummins, E. Muchmore, and M. Houghton, submitted for publication), suggesting that these purified HCV envelope proteins display native HCV epitopes.

Animals↗
PubMed1993

[Bronchogenic cyst as a rare differential diagnosis of retroperitoneal tumor].

A retroperitoneal tumor originating from a bronchogenic cyst is an extreme rarity. We report the sixth case of a retroperitoneal bronchogenic cyst in an asymptomatic 38-year-old man who was initially admitted to hospital due to elective herniotomy of a right-sided inguinal hernia. Excluding symptomatic hernia by preoperative, routine-ultrasound we detected left-sided adrenal tumor mass. Computerized tomography and inconspicuous hormone-analysis completed preoperative evaluation. A tumor with 3 cm in diameter above the left adrenal gland, partly solid, partly cystic could be removed by laparotomy incision without complications. Final pathology confirmed diagnosis of a bronchogenic, dysontogenic cyst. Although rare, these cysts should be considered in differential-diagnosis of retroperitoneal tumors.

Adrenal Glands↗
PubMed1993

Morphometric evaluation of neurophysin-immunoreactivity in the human brain: pronounced inter-individual variability and evidence for altered staining patterns in schizophrenia.

The neurohypophyseal peptides vasopressin and oxytocin have a variety of well documented behavioural effects. Accordingly, terminals and receptors that respectively contain or bind these peptides have been identified throughout the central nervous system (CNS) in experimental animals. In this study we have mapped the distribution of neurophysin I and II-immunoreactive structures in the human CNS. Neurophysins are portions of the precursor proteins for vasopressin and oxytocin, and are found specifically in structures that contain these peptides. In addition, we have quantitatively compared neurophysin neurons and fibers in the brains of individuals with no history of neurologic or psychiatric abnormality, and in brains of patients dying with psychotic illness categorized as schizophrenia. These latter brains were collected prior to the advent of pharmacologic treatment and were available from the Vogt collection. Our findings show wide variations of morphometric values obtained for neurophysin-stained structures in different CNS regions in normal subjects, but provide evidence for abnormal values in certain brain areas in untreated schizophrenia, in the hypothalamic paraventricular nucleus, internal pallidal segment and substantia nigra. These findings suggest that the function of vasopressin and/or oxytocin may be disturbed in these brain regions in schizophrenia. Further investigation will be required to establish whether these differences contribute to, or are a consequence of the disease mechanism.

Adult↗
PubMed1992

Diagnosis of hepatitis C virus (HCV) infection using an immunodominant chimeric polyprotein to capture circulating antibodies: reevaluation of the role of HCV in liver disease.

Structural and nonstructural regions of the HCV-encoded polyprotein have been expressed in recombinant yeast, bacteria, or insect cells and used to capture and measure reactive antibodies circulating in different individuals. The putative nucleocapsid protein (C) and nonstructural proteins 3-5 (NS3-NS5) were found to contain the most immunodominant epitopes. The NS3, NS4, and C regions were expressed in yeast in the form of a fused, chimeric polyprotein (C25) and a capture assay for reactive antibody was developed. This anti-C25 assay detects all previously identified HCV-seropositive cases and provides a substantially more sensitive diagnostic for both acute and chronic HCV infections than the current anti-C100-3 (NS4) assay. Anti-C25 was detected more frequently than anti-C100-3 in chronic, transfusion-associated non-A, non-B hepatitis patients from the United States (95% vs. 71%) and Japan (98% vs. 82%), in cryptogenic cirrhosis patients from the United States (62% vs. 28%), and in hepatitis B surface antigen-negative cases of hepatocellular carcinoma from Japan (83% vs. 63%). These data indicate that HCV has a greater role in these liver diseases than was previously thought. In volunteer United States blood donors sampled following the introduction of anti-C100-3 screening, the prevalence of anti-C25 and anti-C100-3 was 0.5% and 0.08%, respectively.

Antigens, Viral↗