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Biomedical subjects

W Weber

Publications and source records attributed to W Weber.

At least 19 recordsLinked to original sources

Determination of the relative configuration of 5,6,7,8-tetrahydromethanopterin by two-dimensional NMR spectroscopy.

The relative configuration of the pterin moiety of 5,6,7,8-tetrahydromethanopterin 1, a coenzyme isolated from methanogenic archaea, has been determined by two-dimensional NMR spectroscopy of N5,N10-methenyl-5,6,7,8-tetrahydromethanopterin 2 to be rel-(6R; 7S; 11R). The complete proton resonance assignment of the pterin moiety of N5,N10-methylene-5,6,7,8-tetrahydromethanopterin 3 is described including the relative stereospecific assignment of the C(14a) methylene protons.

Magnetic Resonance Spectroscopy

[Cancer research in clinical practice. The attentive physician and the family anamnesis].

Astute physicians play an important role in the detection of cancer causes. Their most powerful tool is the family history. It permits the identification of families with unusual cancer clusters. The members of such families can be recruited for research in prevention and molecular genetics. The potential of research in medical practice should be exploited more extensively in the future.

Algorithms

Binding of the H-ras p21 GTPase activating protein by the activated epidermal growth factor receptor leads to inhibition of the p21 GTPase activity in vitro.

There is strong, albeit indirect, evidence for a mitogenic signal transduction pathway comprising growth factors, growth factor receptors, the GTPase activating protein (p120-GAP), and p21ras. To demonstrate a direct physical association between these proteins in the absence of other cell constituents, their interaction was studied in vitro. Our results obtained with homogeneous protein preparations show that the activated epidermal growth factor (EGF) receptor phosphorylates p120-GAP at one site. Phosphorylated p120-GAP remains firmly bound to the receptor at physiological salt concentration; this leads to product inhibition of the receptor kinase activity as shown by diminished autophosphorylation activity and lack of turnover in p120-GAP phosphorylation. Phosphorylated p120-GAP is as active in stimulating the p21ras.GTPase as unphosphorylated GAP. p120-GAP, however, when bound to the EGF receptor is by a factor of 2 less active in stimulating the p21ras.GTPase than free p120-GAP. This effect might contribute to regulate the steady-state level of p21-GTP.

Enzyme Activation

[The significance of the family anamnesis in women with breast carcinoma].

A cancer-related family history was ascertained in 600 women with breast cancer. Prevalence data in the families were compared to the data of the population-based Basel cancer registry. Breast cancer occurrence was increased in first degree female relatives (relative risk: 1.7; 95% confidence interval: 1.4-1.9; p less than 0.0001). Breast cancer risk in relatives decreased with increasing age of the probands. Women at elevated breast cancer risk can be identified by obtaining a family history of breast cancer patients.

Adult

[Respiratory problems in cancer--causes and treatment].

Half of the patients with advanced cancer suffer from shortness of breath. This may be due to the cancer itself, result from its treatment or arise from concurrent conditions. Careful assessment should precede any intervention. Treatment should be directed toward altering the underlying pathological process as far as possible (e.g. tumour reduction or pleural puncture). The relieve of symptoms by reassuring presence and morphine application are the mainstay, when it is not possible to reverse the cause of dyspnea, and can also successfully complement specific therapy.

Anti-Anxiety Agents

The pharmacokinetics of two different concentrations of short-acting insulin, intermediate-acting insulin, and an insulin mixture following subcutaneous injection.

To compare the pharmacokinetics of two different concentrations, containing either 40 or 100 IU/ml of short-acting human insulin (Velasulin HM), intermediate-acting human insulin (Insulatard HM), or an insulin mixture (25% short-acting insulin, 75% intermediate-acting insulin; Mixtard HM), three randomized, single-blind, crossover trials were performed using the euglycemic clamp technique. Eighteen healthy volunteers received insulin of either formulation subcutaneously in each of the studies (15 IU Velasulin, 20 IU Insulatard, or Mixtard). The blood glucose levels were maintained constant by glucose infusions. In the trial using Velasulin, the two different insulin concentrations were equivalent regarding the total absorption [area under the curve (AUC) of serum insulin: 126 +/- 28 and 123 +/- 35 mU/l x 12 h for U40 and U100 (mean +/- SD)], but not in regard to the rate of absorption (t max 1.3 +/- 0.4 and 2.4 +/- 1.0 h for U40 and U100). In the case of Insulatard, total absorption was not equivalent (AUC 153 +/- 35 and 128 +/- 37 ml/l x 24 h for U40 and U100), but the rate of absorption was equivalent (t max 4.8 +/- 2.9 and 5.3 +/- 4.6 h). In the Mixtard series, total absorption was equivalent (AUC 142 +/- 32 and 128 +/- 22 mU/l x 24 h), but the rate of absorption was not (t max 2.2 +/- 0.9 and 3.2 +/- 4.2 h for U40 and U100). The glucose requirement was not equivalent in each of the three series.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Percutaneous sonographic angioplasty. Initial experimental results].

Aim of the present study was to examine in vitro the effects of a new ultrasound catheter system on atherosclerotic and normal vessels before employing the system in humans. 141 attempts were made on 32 vascular preparations obtained at autopsy. The vessels were opened longitudinally within 24 hours of death, dilated with gelatine and were then "treated" in a waterbath using varying degrees of pressure, angle of incidence, sound intensity and duration of sound. Macroscopic and histological examinations of the preparation showed no morphological change in normal vessels except evidence of pressure by the catheter. In particular, there were no perforations of the vessel wall. In atherosclerotic segments there was significant reduction in the size of plaques following treatment.

Angioplasty, Balloon

Evaluation of hepatic function using the pharmacokinetics of a therapeutically administered drug. Application to the immunosuppressant cyclosporin.

A method is presented for the simultaneous estimation of functional hepatic blood flow and intrinsic clearance. The method uses pharmacokinetic data of a therapeutically employed drug and one of its primary metabolites following intravenous and oral administration of the parent compound. When the disposition of the drug is linear, this method can cope with complicated dosage regimens commonly confronted in clinical data. The feasibility of the method was demonstrated in 10 patients who had undergone liver transplantation and were receiving cyclosporin in the immediate postoperative period. Mean hepatic blood flow was estimated to be 0.89 (95% CI: 0.62 to 1.23) L/h/kg and intrinsic cyclosporin clearance as 0.60 (95% CI: 0.49 to 0.72) L/h/kg. Apart from the hepatic parameters, bioavailability and the fraction of the dose absorbed, a detailed pharmacokinetic description of the parent drug and the elimination pharmacokinetics of a primary metabolite are provided. This information not only allows optimisation of individual therapy, but also may be used to compare absorption properties of different pharmaceutical formulations.

Administration, Oral

Lack of pharmacokinetic interactions between moxonidine and digoxin.

The potential for pharmacokinetic interactions between moxonidine and digoxin at steady-state was investigated in 15 healthy male volunteers. Multiple oral doses of 0.2mg moxonidine twice daily and 0.2mg digoxin once daily were administered alone and in combination in a randomised 3-period crossover design. The drugs were administered for at least 5 days. The results indicate that neither moxonidine nor digoxin influences the pharmacokinetics of the other drug under steady-state conditions.

Administration, Oral

[Thromboembolism complications in orthopedics and traumatology. A prospective study of 598 operated patients].

From 1.10.-31.12. 1989, 598 patients who underwent orthopaedic surgery in the Staatliche Orthopädische Klinik were examined by a pre-, intra- and postoperative questionnaire up to 3 months from the date of operation. All patients were separated into 4 groups corresponding to the calculated risk and duration of the operation. 46 patients in Group I, who underwent minor surgery, received 3 x 5000 I.E. Heparin subcutaneously. 243 patients in Group II received besides 3 x 5000 I.E. Heparin, 500 ml HAES 6% preoperatively. They underwent operations of greater intensity and duration at the upper and lower extremities. 302 patients of Group III were given 3 x 5000 I.E. heparin and 500 ml 6% dextrane 60 preoperatively because of severe operations (pelvis, hip). 7 high-risk patients received apart from 3 x 5000 I.E. Heparin subcutaneously 500 ml 6% dextrane 60 preoperatively and 250ml 10% dextrane 40 postoperatively for 5 days. In Group I we had 2.2% thromboembolic complications, whereas in Group II 1.7% and in Group III 3.3% complications with thrombosis and pulmonary embolism occurred. This was proved by pulmonary scintigraphy and phlebography. No such complications were seen in Group IV. The total incidence of deep vein thrombosis was 2.0% and of pulmonary embolism 0.5%. These results show the importance of preoperative risk check and individual prophylaxis of thromboembolic complications in orthopaedic and traumatologic surgery.

Adolescent

The pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in haemodialysis patients.

1. The pharmacokinetics of and therapeutic response to recombinant human erythropoietin (rcEPO) were studied in 12 patients under chronic haemodialysis on a thrice weekly intravenous rcEPO treatment scheme. The kinetics of rcEPO were also assessed after a subcutaneous injection during the initial period and during maintenance treatment. RcEPO was measured in plasma by radioimmunoassay. 2. After the first i.v. dose plasma erythropoietin concentrations were best described by a monoexponential disposition function with a mean (+/- s.d.) elimination half-life of 5.4 +/- 1.7 h. The volume of distribution was 70 +/- 5.2 ml kg-1 and the clearance was 10.1 +/- 3.5 ml h-1 kg-1 (n = 12). 3. After 3 months of continuous therapy, the plasma half-life of rcEPO decreased by 15% (P < 0.05, mean half-life during steady state: 4.6 +/- 2.8 h), while mean clearance and volume of distribution remained constant. 4. After the first s.c. injection the mean (+/- s.d.) absorption time was 22 +/- 11 h and systemic availability was 44 +/- 7%. 5. Changes in haemoglobin concentrations were described by a linear additive dose-response model, defined by an efficacy constant (Keff) and the mean erythrocyte lifetime (MRTHb). The sample mean (+/- s.d.) Keff was 0.043 +/- 0.017 g dl-1 Hb per 1000 units rcEPO and MRTHb was 10.02 +/- 1.75 weeks. The net effect of rcEPO treatment was described by the area under the unit-dose-response curve (AUEC) with a mean (+/- s.d.) value of 0.45 +/- 0.23 g dl-1 weeks. 6. RcEPO clearance showed a significant positive correlation (r2 = 0.41) with the effectiveness of rcEPO therapy, as measured by the parameters Keff or AUEC.

Adult

[Tumor diseases in families of 600 breast cancer patients with special reference to familial adenocarcinomatosis and the Li-Fraumeni-/SBLA syndrome].

In some families breast cancer aggregates as the predominant site-specific neoplasia and in others in association with defined malignancies. In the case of familial adenocarcinomatous (Lynch II-syndrome) it occurs together mainly with colorectal and endometrial carcinoma whereas in the case of the Li-Fraumeni/SBLA-syndrome it belongs to a wider spectrum including sarcoma, brain tumors, lung and laryngeal cancer, leukaemia and adrenocortical carcinoma. The occurrence of these malignancies is reported as they were observed in the families of 600 women suffering from breast cancer.

Adenocarcinoma

[Late results following implantation of aortic bifurcation prosthesis].

From January 1976 to December 1986 181 patients with chronic arterial occlusive disease were provided with an Y-prosthesis of the aorta. In a retrospective study we reviewed the history of these patients. From 130 (72%) patients we obtained information about the further course of the disease, 83 (46%) patients were reexamined. Depending on the preoperative stage (Fontaine-Ratschow classification) of the chronic arterial occlusive disease, patients in higher stages had a greater benefit from the implantation by shifting into a more satisfactory stage. The majority of patients without any postoperative complaints (48%) belonged to the group, preoperatively classified into stage II B. Depending on the type of occlusion the best results were obtained in unique occlusions of the aorto-iliac vascular segment. 50% of the reexamined patients had no complaints although in 61% of these cases the superficial femoral artery was occluded in the mean time. 47 patients deceased during the interval of observation. In most cases death was caused by other manifestations of the basic disease (e.g. cardiac infarction or cerebral apoplexy). The 10-year-survival rate was 59%. The majority of patients with chronic occlusive disease of the pelvic arteries profited from the implantation of an aortal Y-prosthesis. The long-term success of this operation with its low lethality depends on the preoperative stage and the extent of the occlusive process.

Aorta, Abdominal

[The venous aneurysm].

Venous aneurysms are rare: only 311 cases of venous aneurysms and 56 cases of aneurysms in vein transplants have been reported since 1939 to date. 62% of the patients suffering from venous aneurysms were less than 40 years of age. The most frequently involved vessels were the internal jugular vein (n = 56), the portal vein (n = 28), the v. saphena magna (n = 30) the popliteal vein (n = 23), the azygos vein (n = 22) and the vena cava superior (n = 20). The diameters of the aneurysms were between 1 and 16 cm. Symptoms, if at all noticeable, depend on the localisation of the aneurysm, but they are unspecific in the majority of cases. The most frequent finding was the space- occupying growth seen in 190 patients (52%). Pulmonary embolisms originating from venous aneurysms were seen in 19/311 (6.1%), a rupture of an aneurysm in 4/311 (1.2%) of the venous aneurysms and 5/56 (8.9%) of the aneurysms in transplant veins, respectively. and were fatal in 1 (0.3%) and 2 (3.6%) of the cases, respectively. Of the 205 patients who were operated on, 3 (1.5%) died from intraoperative complications.

Abdomen

[The percutaneous irradiation of osteolytic bone metastases--a course assessment].

Percutaneous radiotherapy is the most effective modality for treatment of metastatic bone cancer. Local irradiation improves overall quality of life by relieving pain in most patients. It also helps preventing complications as pathological fractures in lytic bone lesions by new bone formation. In a retrospective study on 100 patients, irradiated for lytic bone metastases, the radiotherapeutic effect on alleviation of pain and on recalcification rate was investigated. In our experience in 84% of the cases pain and disability associated with bone metastases could be decreased. 38% of the patients had complete relief of symptoms. A correlation between subjective therapy effect and histology of the primary tumor was not demonstrated. Remineralization was found in 67% of all irradiated skeletal areas (n = 137) (recalcification rate in breast cancer 77%, in bronchial carcinoma 27%, and in renal cell carcinoma 25%). After a total dose of 30 Gy reduction of the metastases-associated pain was achieved in 81% of the cases and remineralization was observed in 70% of the cases.

Adult