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Biomedical subjects

U Siebert

Publications and source records attributed to U Siebert.

At least 37 records · Page 2Linked to original sources

Primary cervical cancer screening by self-sampling of human papillomavirus DNA in internal medicine outpatient clinics.

BACKGROUND: We determined whether testing of self-collected vaginal swabs for human papillomavirus (HPV) DNA can be used to screen for cervical disease within internal medicine outpatient clinics. PATIENTS AND METHODS: In this prospective study, 560 patients visiting two referral outpatient clinics for internal medicine were asked to take an HPV self-sample. Acceptability of self sampling, HPV prevalence and cervical intraepithelial neoplasia (CIN) detection rate were evaluated. RESULTS: 435 women (78%) performed HPV self-sampling; 1.5% considered self-sampling to be difficult. 134 women (31%) tested positive for high-risk type of HPV. There were significant differences between HPV-positive and -negative women with respect to the following: mean age (42 versus 46 years), number of women aged <16 years at first coitus (35% versus 23%) and history of drug abuse (8.3% versus 2.6%). Colposcopy could be performed for 70 HPV positive women: CIN 1-3 was identified in 24%. Two of 52 women with HPV-negative results undergoing colposcopy had biopsy-confirmed CIN 1. Test performance for detection of CIN 2-3 after correction for verification bias: sensitivity, 100%; specificity, 71%; negative predictive value, 100%; positive predictive value, 10%. HPV persistence was associated with a 5.7-fold risk of CIN 2-3 detection at follow-up. CONCLUSIONS: Self-assessment for HPV DNA is an easy, feasible and well-accepted method for HPV testing and for cervical cancer screening in internal medicine outpatient clinics.

Adult↗

Identification and molecular characterization of beta-hemolytic streptococci isolated from harbor seals (Phoca vitulina) and grey seals (Halichoerus grypus) of the German North and Baltic Seas.

Bacteriological investigations of seals of the German North and Baltic seas resulted in the isolation of bacteria of the genus Streptococcus belonging to Lancefield's serological groups C, F, and L. According to biochemical, serological, and 16S ribosomal DNA analysis, the group C and group F streptococci were identified as Streptococcus phocae. The group L streptococci could be classified as Streptococcus dysgalactiae subsp. dysgalactiae.

Animals↗

Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis.

OBJECTIVE: To assess the additional diagnostic and clinical value of the second test generation of anti-cyclic citrullinated peptide antibodies (CCP2) compared with rheumatoid factor isotypes (IgG-RF, IgA-RF, IgM-RF) in patients with rheumatoid arthritis. METHODS: This was a prospective study on 715 patients: rheumatoid arthritis (n = 295), degenerative or other inflammatory joint disease (n = 163), connective tissue disease or vasculitis (n = 103), and healthy controls (n = 154). Sera from each subject were tested for CCP2 and RF isotypes by enzyme linked immunosorbent assay (ELISA). Agreement with clinical indices such as disease activity, joint destruction, disease duration, and other laboratory tests was assessed. Sensitivity and specificity of the tests were evaluated taking the clinical diagnosis as the gold standard. RESULTS: Highest sensitivity was found for IgM-RF (66.4%) and CCP (64.4%). Highest specificity was achieved by CCP (97.1%) and IgG-RF (91.0%). In rheumatoid patients with high disease activity or severe joint damage, CCP was more often present (81.4% and 83.6%) than all RF isotypes. Of special diagnostic value was the detection of positive CCP in 34.5% of all patients with rheumatoid arthritis when all measured RF isotypes (IgG-RF, IgA-RF, and IgM-RF) were negative. CONCLUSIONS: As a screening method for rheumatoid arthritis the IgM-RF and the CCP assays are superior to other RF isotypes. Positivity in the highly specific CCP ELISA supports the diagnosis of rheumatoid arthritis. CCP proved to be a powerful diagnostic tool, especially in ambiguous cases or RF negative patients with rheumatoid arthritis.

Adult↗

A randomized comparison of 4 doses of intracoronary adenosine in the assessment of fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) is a measure of coronary stenosis severity that is based on pressure measurements obtained at maximal hyperemia. Therefore, achievement of maximal vasodilatation of the coronary microcirculation is a prerequisite for the measurement of FFR. The study was designed to address the hypothesis that intracoronary adenosine yields more complete vasodilatation of the coronary microcirculation when high doses are used, resulting in a more accurate FFR measurement. METHODS: Thirty-six patients with 43 moderate lesions underwent determination of FFR during cardiac catheterization. FFR was calculated in all lesions as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (16, 24, 32 and 40 microg for both coronary arteries) were administered in a randomized fashion. RESULTS: No adverse events occurred with any intracoronary adenosine bolus. At baseline there were no significant differences for mean aortic and distal coronary pressure, heart rate as well as FFR values between the different doses. FFR was not significantly altered from the different incremental adenosine doses. However, in 27 (63%) out of 43 lesions there was a further reduction of FFR up to 0.23 when a dose >16 microg was injected. CONCLUSIONS: This study suggests that doses of adenosine up to 40 microg are safe and can be used to achieve a more pronounced vasodilatation in individual patients compared to the standard doses. This may have therapeutic impact with FFR values near cut-off points in patients undergoing diagnostic coronary angiography as well as in patients in whom FFR is used to assess the outcome of interventions.

Adenosine↗

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↗

Parapoxvirus infection in harbor seals (Phoca vitulina) from the German North Sea.

In the summer of 2000, proliferative lesions of the skin and oral mucosa were observed in 26 young harbor seals (Phoca vitulina) from a rehabilitation center in Schleswig-Holstein, Germany. Verrucose, roundish nodules, approximately 1-2 cm in diameter, were presented in the oral cavity, especially on the tongue. Some animals developed similarly sized spherical dermal elevations with ulceration on flippers, chest, neck, and perineum. Necropsy of one animal showed multifocal, verrucose nodules in the oral cavity and a mild tonsillitis. Histologically, the nodules were characterized by ballooning degeneration of the outer parts of the spiny layer and stratum granulosum, with large eosinophilic cytoplasmic inclusions and a perivascular to interstitial lymphohistiocytic infiltration accompanied by fibroblastic proliferation and neovascularization. Negative staining of mucosal tissue homogenates demonstrated parapoxvirus-like particles. The presence of parapoxvirus was confirmed by polymerase chain reaction, using primers specific for parapoxvirus of ungulates. By in situ hybridization, using a parapox-specific, digoxigenin-labeled DNA probe, abundant parapoxvirus DNA-positive epithelial cells were detected in the stratum granulosum and the outer parts of the spiny layer. There was no parapoxvirus-positive signal in the adjacent submucosa. Although DNA analysis revealed that the causative agent can clearly be distinct from terrestrial parapoxviruses, lesions resembled parapoxvirus infections in other terrestrial species, and the pattern of virus DNA distribution indicated a direct effect of the virus on keratinocytes. In contrast, changes in the corium may be considered an indirect response mediated by the virus or the immune system.

Animals↗

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↗