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Biomedical subjects

U Siebert

Publications and source records attributed to U Siebert.

At least 19 recordsLinked to original sources

Cost effectiveness of peginterferon alpha-2b plus ribavirin versus interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C.

BACKGROUND: Peginterferon alpha-2b plus ribavirin therapy in previously untreated patients with chronic hepatitis C yields the highest sustained virological response rates of any treatment strategy but is expensive. AIMS: To estimate the cost effectiveness of treatment with peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of patients with chronic hepatitis C. METHODS: Individual patient level data from a randomised clinical trial with peginterferon plus ribavirin were applied to a previously published and validated Markov model to project lifelong clinical outcomes. Quality of life and economic estimates were based on German patient data. We used a societal perspective and applied a 3% annual discount rate. RESULTS: Compared with no antiviral therapy, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 4.2 and 4.7 years, respectively. Compared with standard interferon alpha-2b plus ribavirin, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 0.5 and by 1.0 years with incremental cost effectiveness ratios of 11,800 euros and 6600 euros per quality adjusted life year (QALY), respectively. Subgroup analyses by genotype, viral load, sex, and histology showed that peginterferon plus weight based ribavirin remained cost effective compared with other well accepted medical treatments. CONCLUSIONS: Peginterferon alpha-2b plus ribavirin should reduce the incidence of liver complications, prolong life, improve quality of life, and be cost effective for the initial treatment of chronic hepatitis C.

Adult↗

Pyogranulomatous myocarditis due to Staphylococcus aureus septicaemia in two harbour porpoises (Phocoena phocoena).

Staphylococcus aureus septicaemia was diagnosed in a dead, stranded harbour porpoise from the German Baltic Sea and in a live harbour porpoise by-caught in inner Danish waters and taken into captivity. Lesions included pyogranulomatous myocarditis, necrotising suppurative bronchopneumonia, pyelonephritis, osteomyelitis and leptomeningitis, and abscesses in lymph nodes and skeletal muscles. The captive animal had fibrinous suppurative epicarditis and pyogranulomatous myocarditis with abscesses. In both animals the organism was suspected to have entered through skin lesions or via the respiratory tract.

Animals↗

Global distribution of halogenated dimethyl bipyrroles in marine mammal blubber.

Four halogenated dimethyl bipyrroles (HDBPs), hypothesized to be naturally produced, were quantitated in marine mammal blubber from a number of species obtained from various locations worldwide. HDBPs were found in samples from all locations studied. Concentrations of total HDBPs (SigmaHDBPs) ranged from 0.4 ng/g lipid weight in ringed seals (Phoca hispida) from the White Sea to 2,540 ng/g lipid weight in Dall's porpoise (Phocoenoides dalli) from the northwestern North Pacific Ocean. At their highest levels, SigmaHDBPs made up 11% of the total quantitated organohalogen body burden of adult male Dall's porpoises. In two beluga (Delphinapterus leucas) data subsets, it was found that males contained significantly higher concentrations of SigmaHDBPs than females. No significant effects of age or sex on SigmaHDBPs were observed in harbor seal (Phoca vitulina) and bowhead whale (Balaena mysticetus) data subsets. The geographical distribution of concentrations did not resemble that of the ubiquitous anthropogenic organohalogen, polychlorinated biphenyl congener CB-153. Higher concentrations of HDBPs and different patterns of congeners were observed in samples from Pacific as opposed to non-Pacific Ocean influenced environments. Concentrations of HDBPs in beluga from the Arctic and St. Lawrence River were similar. Their high abundance in north Pacific Ocean biota and widespread occurrence suggest that HDBPs undergo extensive transport from a source located primarily in the Pacific Ocean. Evidence from HDBP congener patterns indicates that both ocean currents and atmospheric transport likely play a role in the movement of HDBPs. These results imply that HDBPs and anthropogenic organohalogens have different sources and support the natural production hypothesis.

Adipose Tissue↗

Characterization of sealpox virus, a separate member of the parapoxviruses.

A disease outbreak characterized by lesions of the skin and mucosa of the oral cavity was recognized in harbor seals ( Phoca vitulina) from the German North Sea. Using electron microscopy typical parapoxvirus particles were observed. The presence of parapoxvirus was confirmed by PCR and nucleotide sequencing of part of the putative major envelope protein coding gene. Comparative sequence analysis revealed that the virus from seal is significantly different from the established parapoxvirus species Orf virus, Bovine papular stomatitis virus, Pseudocowpox virus, and Parapoxvirus of red deer in New Zealand. The results of our analysis provide evidence for inclusion of the seal parapoxvirus as member of a separate species within the genus Parapoxvirus.

Amino Acid Sequence↗

Efficacy, routine effectiveness, and safety of horsechestnut seed extract in the treatment of chronic venous insufficiency. A meta-analysis of randomized controlled trials and large observational studies.

BACKGROUND: Safe and effective oral therapies for chronic venous insufficiency (CVI) would provide an important alternative to mechanical compression treatment. Several narrative reviews and one systematic review have summarized the efficacy of horse chestnut seed extract (HCSE), but to our knowledge no systematic review has included data from both randomized controlled trials (RCTs) and large-scale observational studies regarding outcomes as well as adverse events. METHODS: Using a systematic literature search, we identified 13 RCTs of CVI (1,051 patients) and 3 observational studies (10,725 patients) that met our inclusion criteria. Examined outcomes were leg volume, ankle and calf circumference, edema, pain, sensation of tension, swelling, leg fatigue/heaviness, calf cramps, and itching. Random and fixed effect models were used to pool outcomes and adverse events separately for RCTs and observational studies. RESULTS: Overall, the RCTs indicated that HCSE improved symptoms in patients with CVI. Compared to placebo, HCSE reduced leg volume by 46.4 ml (95% CI, 11.3-81.4 ml) and increased the likelihood of improvement in leg pain 4.1-fold (95% CI, 0.98-16.8). Similarly, improvement probabilities were increased 1.5-fold (95% CI, 1.2-1.9) for edema and 1.7-fold (95% CI, 0.01-3.0) for itching. There was insufficient evidence to demonstrate HCSE's effect on leg fatigue/heaviness or calf cramps. Observational studies showed significant effectiveness regarding pain, edema, and leg fatigue/heaviness. No severe adverse events were reported, and HCSE did not significantly increase mild adverse events. CONCLUSIONS: Based on meta-analyses of RCTs and observational studies, HCSE appears to be an effective and safe treatment for CVI. Further RCTs and carefully conducted large-scale observational studies are required to evaluate the long-term effectiveness and safety of HCSE in routine settings.

Adolescent↗

Evidence of infectious diseases in harbour porpoises (Phocoena phocoena) hunted in the waters of Greenland and by-caught in the German North Sea and Baltic Sea.

The pathological, microbiological and serological findings in harbour porpoises hunted in Greenlandic waters were compared with the findings in animals accidentally caught in fishing gear in the German North Sea and Baltic Sea. The body condition of the Greenlandic animals was good, whereas nine of 23 German harbour porpoises were moderately to markedly emaciated. Both groups were infested with parasites. In the Greenlandic animals parasitism of the aural peribullar cavity with Stenurus minor, of the liver and pancreas with Orthosplanchnus mironovi, of the lungs with Halocercus species and of the subcutaneous and mammary tissue with Crassicauda species was generally associated with a mild inflammatory response. No diseases associated with bacteria were identified in any of the Greenlandic harbour porpoises. In the porpoises from the German North Sea and Baltic Sea, parasites were present in the aural peribullar cavity (S minor), liver (Campula oblonga), first and second gastric compartment (Anisakis simplex) and in the lungs (Pseudalius inflexus and Torynurus convolutus). Moderate to marked pulmonary parasitism and suppurative pneumonia, not observed in the Greenlandic porpoises, were present in 11 and 10, respectively, of the 23 German porpoises. The suppurative pneumonia was attributed to bacterial infection with beta-haemolytic streptococci and Escherichia coil var haemolytica. Four Greenlandic and 10 German porpoises had positive porpoise morbillivirus-specific antibody titres suggesting that the virus was circulating in both populations.

Animals↗

Bioaccumulation of polychlorinated biphenyls (PCBs) and dichlorodiphenylethane (DDE) methyl sulfones in tissues of seal and dolphin morbillivirus epizootic victims.

Polychlorinated biphenyl (PCB) and dichlorodiphenylethane (DDE) methyl sulfone (MSF) metabolites possess high affinities for binding two homologous 16,000 Da homodimeric receptor proteins in the lung (Clara cell secretory protein, CCSP) and the uterus (uteroglobin, UG), leading to selective bioaccumulation of MSFs in these tissues. As marine mammals are highly exposed to organochlorines, concentrations of PCBs, PCB MSFs, DDT, and DDE MSF were analyzed in blubber, lung, and uterus samples from harbor seal (Phoca vitulina) and striped dolphin (Stenella coeruleoalba) morbillivirus epizootic victims to investigate uterine and lung MSF accumulation. Mean uterus concentrations of PCB MSFs and DDE MSF in harbor seals were 0.61 and 0.04 microg/g lipid weight and in striped dolphins 0.05 and 0.01 microg/g lipid weight. Mean lung concentrations of PCB MSFs and DDE MSF in harbor seals were 0.96 and 0.02 microg/g lipid weight and in striped dolphins 0.16 and 0.01 microg/g lipid weight. To ascertain whether uterine and lung bioaccumulation of MSFs is possible due to the presence of CCSP and UG in seals, CCSP and UG proteins in uterine flushings and in uterine and lung and epithelial tissue from Baltic gray and ringed seals were characterized using gel electrophoresis and Western blotting techniques. UG- and CCSP-like proteins with molecular weights of 16,000 Da were resolved in all samples. This is the first demonstration of this protein in any marine mammalian species. The toxicological implications of MSF binding with UG and CCSP in marine mammals are discussed.

Adipose Tissue↗

Immunohistochemical investigation of the cross-reactivity of selected cell markers from various species for characterization of lymphatic tissues in the harbour porpoise (Phocoena phocoena).

To facilitate a detailed investigation of cetacean lymphoid organs, 13 canine-, six bovine-, one equine-, one human- and four killer whale-specific monoclonal antibodies (mAbs) directed against cell surface antigens of the haematopoietic system (including CD2, CD4, CD8, CD45R, MHC class II, granulocyte, thrombocyte, pan-T cell and B-cell antigen), as well as a mAb and a polyclonal antibody (pAb) directed against the -peptide of the human CD3 complex, were tested for immunohistochemical cross-reactivity on frozen or formalin-fixed, paraffin wax-embedded lymphatic tissues of harbour porpoises. Eight of 26 mAbs and the pAb showed a specific reaction with harbour porpoise cells. Lymphocytes in T-cell compartments were labelled by the mAb and the pAb directed against the CD3 complex and by two killer whale mAbs specific for CD2 antigen. CD45R, labelled by a killer whale-specific mAb, was strongly expressed on B and weakly on T cells. MHC class II antigen, recognized by killer whale- and bovine-specific mAbs, was expressed on B and T cells. A canine MHC class II-specific mAb recognized an epitope on the surface of antigen-presenting cells and B lymphocytes. An anti-equine-pan-leucocyte marker labelled the majority of cells in B- and T-cell compartments. Thus, with leucocyte antigen markers from various species, it is now possible to determine the phenotype of lymphocytes in normal and diseased lymphoid organs of harbour porpoises.

Animals↗

Demonstration of the healthy worker survivor effect in a cohort of workers in the construction industry.

OBJECTIVES: To assess the potential of a healthy worker survivor effect due to differential occupational mobility in a cohort of construction workers. METHODS: A cohort of 10 809 male employees in the German construction industry aged 15-64 years was followed up for occupational mobility, early retirement due to permanent disability, and total mortality from 1986 to 1994. Using the Cox's proportional hazards model of relative rates (RRs) with 95% confidence intervals (95% CIs) of occupational mobility, early retirement and total mortality were estimated according to medical diagnoses at baseline after adjustment for various covariates. RESULTS: During follow up, 2472 subjects changed employment, 359 employees were granted a disability pension for health reasons and 188 subjects died. A wide range of chronic diseases was associated with increased rates of early retirement and total mortality but not occupational mobility. However, a healthy worker survivor effect was identified related to disorders of the back and spine (ninth revision of the international classification of diseases, ICD-9, code 720-4), a common predictor of both occupational mobility (RR 1.17, 95% CI 1.04 to 1.32) and early retirement (RR 1.50, 95% CI 1.20 to 1.88). In total, there were about as many events of occupational changes (n = 41) as events of early retirement due to permanent disability (n = 39) significantly attributable to disorders of the back and spine. Differential occupational mobility preceded differential early retirement due to permanent disability by more than one decade. CONCLUSIONS: These findings show the need to consider a healthy worker survivor effect due to occupational mobility in occupational epidemiological research. Furthermore these results underline the necessity of further health promotion targeting work related conditions in the construction industry.

Adolescent↗

Impact of social support, cynical hostility and anger expression on progression of coronary atherosclerosis.

OBJECTIVES: This prospective cohort study of patients with coronary artery disease (CAD) sought to determine the impact of social support, anger expression and cynical hostility on progression of coronary atherosclerosis as shown by angiography. BACKGROUND: Low social support, high levels of expressed anger and cynical hostility are correlated to increased CAD morbidity and mortality. However, the impact of these factors, alone or together, on progression of human coronary atherosclerosis is unknown. METHODS: Of 223 patients with CAD documented by standardized angiography at baseline, 162 had a second angiogram after two years. An expert panel who had no knowledge of the patients' characteristics evaluated the films pairwise to determine disease progression. At baseline, all patients were asked to answer three self-report questionnaires: questions concerning emotional social support, the State-Trait-Anger-Expression Inventory (STAXI) and the Cook-Medley cynical hostility scale. Each patient's clinical and laboratory status was followed. RESULTS: Questionnaires and angiographic follow-up data were available for 150 patients. Bivariate analysis of the psychological variables showed a higher risk of progression only for patients who scored high on STAXI anger-out or low on social support. In the multivariate analysis, when adjusting for confounding variables and examining the interaction between psychological variables, only patients with both high anger-out and low social support were at highly increased risk for progression (odds ratio 30, confidence interval [CI] 5.5 to 165.1; RR 3.19). CONCLUSIONS: Patients with CAD and low emotional social support who express anger outwardly are at a highly increased risk of disease progression, independent of medication or other risk factors.

Anger↗

Immunohistological and serological investigation of morbillivirus infection in harbour porpoises (Phocoena phocoena) from the German Baltic and North Sea.

The role of morbillivirus infection as a cause of disease or death in harbour porpoises (Phocoena phocoena) from the German North and Baltic Sea was investigated by serology, histology and immunohistochemistry. Blood and tissue samples of lung, brain and lymph nodes from 74 stranded or by-caught harbour porpoises from German waters were collected between 1991 and 1997. According to dentinal growth layers and body length, animals were grouped into four age classes (neonates, 0-1, 1-4, 4-16 years of age). Formalin-fixed, paraffin-embedded sections were stained by hematoxylin and eosin (HE). Immunohistology was done in all lung tissues using the avidin-biotin-peroxidase technique and a polyclonal canine distemper virus (CDV) nucleoprotein-specific antibody, which cross-reacts with porpoise morbillivirus (PMV) antigen. A virus neutralization assay for detection of (Onderstepoort-strain) CDV- and PMV-specific antibodies was performed. Due to the cytotoxicity of some sera, only titres of 1:20 or greater were considered positive. PMV or CDV-specific neutralizing antibody titres were found in 88 and 50% of the animals, respectively. Titres were always highest against PMV indicating infection with a homologous porpoise virus strain. There were no significant differences in neutralizing antibody titres between animals of the different age groups. No histological lesions specific for morbillivirus infection were detected and by immunohistology all cases were negative for morbillivirus antigen. The absence of morbillivirus antigen and the lack of characteristic morbillivirus-specific lesions showed that morbillivirus infection was not a cause of death or illness in the investigated population. However, the high incidence of PMV-specific antibodies in all age groups indicated a continuous spread of infection with a morbillivirus among harbour porpoises from the German Baltic and North Sea.

Age Factors↗

Reproducibility of neointima quantification with motorized intravascular ultrasound pullback in stented coronary arteries.

BACKGROUND: Intravascular ultrasound (IVUS) imaging has shown excellent reproducibility immediately after coronary stent implantation. However, the variability of measurements in lesions late after stent implantation, when neointima formation is present, has not been studied. Neointimal tissue is generally low echogenic and thus difficult to quantify. We therefore sought to analyze the reproducibility of morphometric measurements late after stent implantation. METHODS AND RESULTS: Fifty consecutive patients were investigated 6 months after Palmaz-Schatz stent implantation (motorized catheter pullback 0.5 mm/s). Two experienced investigators independently identified the stent area, lumen area, and neointimal area at different sites within the stent. Planimetric measurements were performed with commercially available software. Correlation coefficient and mean difference for corresponding measurements were calculated for the intraobserver and interobserver comparisons. Variability for the intraobserver and interobserver comparisons was similar. Observer agreement regarding the presence of neointimal hyperplasia was as high as 71% (interobserver comparison 62%). The mean difference for neointima area was 0.06 +/- 1.5 mm(2) (-0.6 +/- 1.5 mm(2)); mean differences for lumen area were 0.02 +/- 0.19 mm(2) (0.03 +/- 0.17 mm(2)) and for stent area 0.01 +/- 0.09 mm(2) (-0.02 +/- 0.12 mm(2)) (values for interobserver comparison are given in parentheses). Correlation between measurements was high for all structures: correlation coefficients were 0.66 (0.69) for neointima, 0.94 (0.95) for lumen, and 0.95 (0. 91) for stent area. CONCLUSIONS: Morphometric measurements of IVUS investigations with motorized IVUS pullback late after stent placement show good reproducibility. Intraobserver variability and interobserver variability are low. Differences for corresponding measurements were more pronounced for neointima area. Motorized catheter pullback guarantees high reliability of IVUS measurements and should be used routinely for clinical IVUS studies.

Aged↗

Genital diseases in the peruvian dusky dolphin (Lagenorhynchus obscurus).

Ovarian cysts and one ovarian tumour, uterine tumours, vaginal calculi, abscesses of the broad ligament or undetermined testicular lesions were observed in 25 out of 502 female and male dusky dolphins (Lagenorhynchus obscurus) caught off Peru in 1985-1987 or 1993-1994. Tentative or definitive diagnoses included Graafian follicle cysts, luteinized cyst, ovarian parasitic granulomatous inflammation, dysgerminoma, leiomyoma, fibroleiomyoma and chronic fibrino-suppurative inflammation of the broad ligament. All lesions described represented first reports for L. obscurus, and the diagnosis of dysgerminoma was the first in a cetacean. It is also the first time that trematode eggs have been reported in the ovaries of cetaceans and that a vaginal calculus has been encountered in a sexually immature cetacean. The finding of struvite as a major component in two vaginal calculi suggested an infectious aetiology. Of 11 mature females with ovarian tumour or cysts or uterine tumours, only one (9.1%) was pregnant, i.esignificantly less than the expected pregnancy rate (53.3% in a random sample of Peruvian dusky dolphins). Several females with ovarian or uterine lesions and males with aberrant testes were large animals. It is possible that some of these lesions were associated with normal senescence of the reproductive system.

Animals↗

Predictors of reduced coronary flow reserve in heart transplant recipients without angiographically significant coronary artery disease.

BACKGROUND: Determination of coronary flow reserve (CFR) is increasingly used to assess the functional significance of cardiac allograft vasculopathy. Although the relation between CFR and angiographically defined vasculopathy has been studied extensively, little is known about other factors determining CFR in heart transplant recipients without significant lesions by coronary angiography. METHODS: Sixty consecutive patients were studied 0.5 to 148 months after heart transplantation with intracoronary Doppler and intravascular ultrasound. An endothelium-independent CFR< or =2.5 was defined as abnormal. Stepwise logistic regression analysis was used to identify factors (demographic data of donor and recipient, lipid profile, epicardial vessel morphology by intravascular ultrasound, left ventricular hypertrophy, acute rejection episodes, and hemodynamics) potentially associated with a reduced CFR. RESULTS: Only the presence of left ventricular hypertrophy (48% vs. 14%, P=0.007 and P=0.023, bivariate and multivariate analysis, respectively) and higher donor ages (41+/-12 vs. 29+/-11 years, P=0.002 and P=0.013, bivariate and multivariate analysis, respectively) showed an independent association with an abnormal flow reserve. CFR in patients with left ventricular hypertrophy was reduced due to higher baseline flow velocities (27+/-11 vs. 20+/-6 cm/sec, P=0.004). Furthermore, resting flow velocity increased as a function of donor age (r=0.264, P=0.047), while hyperemic flow velocity was not different. Other patient characteristics and hemodynamics did not affect CFR. CONCLUSION: The presence of left ventricular hypertrophy and higher donor ages independently contribute to a reduced CFR in patients after heart transplantation. This reduction in CFR is due to elevated baseline flow velocities rather than to a change in hyperemic flow velocities. These findings should be taken into account for the interpretation of reduced CFR values obtained by intracoronary Doppler in heart transplant recipients without angiographically overt coronary lesions.

Adult↗