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Biomedical subjects

M Seifert

Publications and source records attributed to M Seifert.

At least 73 records · Page 4Linked to original sources

Clinical presentation and long-term follow-up of athletes with exercise-induced vasodepressor syncope.

The purpose of this study is to report on a series of patients who were referred for evaluation of syncope that occurred during or immediately after exercise and in whom a diagnosis of vasodepressor syncope was established (9 women and 8 men; mean age of 28 +/- 17 years). The approach to management was individualized in each patient. All patients were monitored to determine the frequency and type of recurrent symptoms. The mean age at onset of symptoms was 23 +/- 16 years. In 10 patients syncope occurred only in association with exercise. Pharmacologic therapy was successful in normalizing the patients' response to upright tilt in each of the 10 patients in whom it was attempted. During a mean follow-up period of 35 +/- 9 months, none of the patients placed on pharmacologic therapy has had recurrent syncope. Seventeen (88%) of 19 patients have resumed participation in athletics. The results of this study demonstrate that vasodepressor syncope is a cause of syncope in athletes and that patients with exercise-related vasodepressor syncope can safely continue to participate in athletics.

Adolescent↗

Glycosylation analysis of a polyreactive human monoclonal IgG antibody derived from a human-mouse heterohybridoma.

Glycosylation of the human monoclonal IgG1 lambda antibody (mAb) CBGA1 was analysed by lectin blotting. The CBGA1 antibody binds to several antigens including donor self antigens, as detected by ELISA immunoblotting techniques and an erythrocyte binding assay. The mAb producing cell line was obtained by EBV transformation of peripheral blood lymphocytes of a healthy donor followed by fusion to the heteromyeloma cell line, CB-F7. The resulting heterohybridoma was cultivated in a hollow fibre bioreactor system. A bulk pool of 0.9 g antibody was produced. Fab and Fc fragments of the purified mAb were prepared and analysed. A noteworthy heterogeneity of CBGA1 and its fragments in SDS-PAGE and IEF was detected. We found glycosylation in the Fab fragment of CBGA1 in addition to the conserved glycosylation site in the Fc fragment at Asn 297. Fab glycosylation was detected in both the Fd region and the lambda-chain. The glycosylation pattern of the gamma-chain differs from that of the lambda-chain. Sequence analysis of the VH gene shows a potential N-glycosylation site located in framework III at position Asn 75.

Animals↗

Longitudinal analysis of somatic development in paediatric patients with IDDM: genetic influences on height and weight.

Normal growth and development, as well as the prevention of overweight, are major goals in the treatment of paediatric patients with insulin-dependent diabetes mellitus (IDDM). We therefore evaluated longitudinally the anthropometric measurements of height and weight, as well as bone age, in an unselected group of 389 patients with IDDM treated at one institution. In order to identify genetic influences on these parameters, height and weight were determined in 186 unaffected siblings and 177 pairs of parents. At diagnosis, patients were slightly taller than average (median z score: +0.37). During the subsequent course of diabetes, age-adjusted heights decreased progressively for the first 9 years, catching up again after more than 10 years of diabetes. Bone ages were progressively retarded with increasing duration of diabetes. In 76 patients of 18 years or older, median z-score for height was +0.30, not different from their unaffected siblings (median z-score: +0.22). The correlation with midparental height was identical for diabetic and nondiabetic siblings (r = 0.43). In contrast, children with diabetes were significantly heavier (z-score for weight: +0.74 compared to +0.34 in unaffected siblings; p < 0.002). Obesity developed primarily during and after puberty. We conclude that: 1) during the course of diabetes, longitudinal growth is temporarily reduced and maturation is delayed in children with diabetes compared to unaffected siblings. However, this effect of diabetes is transient and small compared to genetic influences on height in an individual child. 2) As a group, children with IDDM become significantly overweight, which is likely to increase the cardiovascular risk during adulthood.

Age Determination by Skeleton↗

Characterization of a B-CLL derived IgM-lambda antibody expressing typical features of a NPAB.

A human IgM-lambda hybridoma (CB-HB) was established from chronic lymphocytic leukaemia (CLL) B-cells. Immunochemical and molecular characterization of the monoclonal antibody (mab) produced by the CB-HB cells offered typical features of natural polyreactive antibodies (NPAPs) found in fetal and healthy adult organisms. In particular, the CB-HB mab reacted with different self and foreign (viral and bacterial) antigens when tested in three independent systems (solid- and fluid-phase ELISA, Western blot) showing binding constants in a range from 1.9 x 10(-7) to 7.5 x 10(-8) mol/l to four antigens chosen. In addition, the CB-HB mab binding could be inhibited by a rabbit polyclonal antiserum specific for a common idiotype (Id 102) on human polyreactive (auto)antibodies. The variable region of the CB-HB mab was found to be encoded by unmutated copies of germline genes. Interestingly, the VH-DP10 (51p1) segment, encoding for the autoantibody-associated G6-cross reactive idiotype frequently expressed on both fetal and malignant B-cells, was found to be used with a V segment (VLO11). Collectively these data imply that cells belonging to the natural polyreactive B-cell repertoire undergo malignant transformation. A stimulation by autoantigens or common foreign antigens may be involved.

Antibodies, Monoclonal↗

[Partial portal vein and mesenteric vein thrombosis in familial protein S deficiency].

Protein S, a vitamin-K dependent glycoprotein is a cofactor of protein-C system, which acts as an inhibitor of the plasmatic coagulation. Protein-S congenital deficiency results in recurrent venous thromboses, atypical locations in portal and mesenteric veins are possible. In our patient the partial thrombosis of the portal vein was diagnosed by computed tomography and angiography. Small bowel ischaemia due to mesenteric vein thrombosis required segmental resection. Post-operatively the patient was heparinized and later phenprocoumon was applied to a long-term therapy.

Adult↗

[Surgical treatment of recurrent stress incontinence: Burch versus lyodura sling operation--a prospective study].

This prospective randomised study involved 52 female patients suffering from recurrent stress urinary incontinence, objectively confirmed by means of clinical incontinence tests and urodynamic examinations. They alternatively underwent colposuspension according to Burch or suburethral sling procedure surgery. Urodynamic and sonographic examinations were carried out before and 2.5 years (i.e. within a range of 2-3) after surgery according to Burch or suburethral sling procedure. There was no significant difference between the two methods with respect to subjective and objective rate of cure, which amounted to 85% of the cases involving colposuspension and 88% of cases involving the suburethral sling procedure. Both methods resulted in a significant improvement of the depression quotient and a significant elevation of the internal urethral meatus (p < 0.05). Apart from an aggravation of urge symptoms in both groups, the patients with surgery according to Burch tended towards enterocele and rectocele in the medium range, whereas urination disorders had to be accepted in the patients operated on according to the sling procedure in the long term.

Collagen↗

Effects of standard breakfast on pharmacokinetics of oral zidovudine in patients with AIDS.

The influence of a standard breakfast on the single-dose pharmacokinetics of zidovudine (AZT) after oral administration of 100 and 250 mg of AZT was studied in 27 subjects with advanced human immunodeficiency virus infection (Centers for Disease Control stage IV). Concentrations of AZT and the 5'-glucuronide metabolite (GAZT) in serum and urine were measured by a high-pressure liquid chromatographic method. Pharmacokinetic analysis was done by an open one-compartment model as well as noncompartmentally. The results were summarized as medians with 50% confidence ranges because of the high degree of interindividual variability. Peak levels in plasma were moderately reduced after administration of 100 mg AZT in the nonfasting group (1.79 mumol/liter in the fasting group [F], 1.12 mumol/liter in the group that received breakfast [B]) and were markedly reduced after administration of 250 mg AZT (6.51 mumol/liter [F], 1.79 mumol/liter [B]). The terminal half-life in plasma was prolonged almost twofold after breakfast with 100 and 250 mg of AZT (100 mg, 36.4 min [F] and 51.6 min [B]; 250 mg, 35.3 min [F] and 63.6 min [B]). Recoveries (AZT and GAZT) in urine varied with both dosages, reflecting more a problem of accounting for the metabolite GAZT in urine than a relevant difference (100 mg, 115% [F] and 76.5% [B]; 250 mg, 71% [F] and 99.4% [B]). Our data suggest that absorption of AZT in human immunodeficiency virus-infected subjects is extremely variable, with a high degree of interindividual differences. Furthermore, breakfast had a marked influence on the absorption of AZT, suggesting that the drug should be taken in a fasting state.

Acquired Immunodeficiency Syndrome↗

Breast cancer and timing of surgery during menstrual cycle. A 5-year analysis of 385 pre-menopausal women.

It has been proposed that the timing of breast-cancer surgery in relation to menstrual phase has a prognostic impact on outcome. We carefully evaluated a combined 2-center series of 385 pre-menopausal women operated on for stage-I and stage-II breast cancer with a median follow-up of 5 years for a possible impact on outcome of the date of their last menstrual period (LMP) before surgery. The distribution of risk factors of the study cohort as well as prognostic indicators corresponded to previously published results. Nodal status, grading, and (in part) hormone-receptor status differentiate well between patient subgroups with high and low risk of relapse and death after breast-cancer surgery. In neither univariate nor multivariate analysis was any impact of the so-called "unopposed" estrogen secretion detected. We did not observe any effect of LMP on long-term survival in any of several prognostic subgroups, in particular in hormone-receptor-positive patients. From our results and from the literature, we conclude that LMP does not provide any prognostic information for outcome after breast-cancer surgery and therefore the proposed modification of scheduling of breast-cancer operations is not justified.

Age Factors↗

[Human papillomavirus (HPV) DNA infections of the uterine cervix].

411 women who had dysplasia, selected from an ambulatory group as well as 240 women from a random control group were examined, by using cervical smears, which were initially diagnosed as human papilloma viruses-DNA (HPV-DNA) of the type 6/11, or 16/18, or 31/33/35. This was achieved by the in-situ nucleic acid hybridisation technique. The results of the HPV-DNA typing were tabulated with the cytological diagnosis (Munich Papanicolaou (Pap.) group-classification). The control group corresponding to Pap.Gr. I, and was HPV-DNA positive in 6 (2.5%) of the 240 cases. The group of 180 patients with a Pap.Gr. II showed a HPV-DNA positive result for 75 cases (41.7%); 57 of 99 cases (57.6%) occurred in Pap.Gr. IIID; 42 of 54 cases 77.8% (L) were found in Pap.Gr. IV (a/b), and 72 of 78 cases (92.3%) appeared in Pap.Gr. V. The HPV-DNA mixed infections became evident as the cellular dysplasia increased. The results of the HPV-DNA positive diagnosis clearly indicate a close correlation with the Pap.Gr.-classification. The HPV-DNA type 16/18 was most frequent in cervical carcinomas (Pap.Gr. V). The cyto-histological control of the 57 HPV-DNA positive cases of the untreated Pap.Gr. IIID showed a regression in 31.6% of the 18 cases after a period of 3 to 6 months (post HPV-DNA typing). These were histologically normal. In 33 cases (57.9%), there was a persisting Pap.Gr. IIID (CIN I/II) and in 6 cases (10.5%) a progredient correlation in Pap.Gr. IV a/b. The Pap. group IV (a/b) was histologically a CIN grade III.

Adolescent↗