Biomedical subjects
Publications and source records attributed to J Schmid.
This report concerns a very rare case of ovarian Sertoli-Leydig cell tumor associated with an evident hyperoestrinism, that occurred in a 67-year-old woman. The clinical and pathological data are presented and discussed.
Following oral administration of 14C labelled 2-[(2-methoxy-4-methylsulfinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS) to the rat, rabbit, dog, rhesus monkey, baboon and man the metabolic pattern in plasma and urine was compared and human urinary metabolites were isolated. None of the animal species investigated shows a metabolic pattern identical to that of man. The plasma of rat, dog and rabbit shows wide variation of metabolites with high amounts of two unpolar metabolites of AR-L 115 BS (sulfoxide), namely M0/2 identical with AR-L 114 BS (sulfone with regard to AR-L 115 BS) and M0/1 identical with AR-L 113 BS (sulfide). In comparison to man the urines of the animals show higher amounts of the sulfone (AR-L 114 BS) and the sulfide (AR-L 113 BS). A main pathway of the metabolism of the pyrido-imidazole of the AR-L 115 BS-type is the oxidative pyridine-ring cleavage leading to N-acetylated 5-aminoimidazoles. Further metabolites are characterised by a hydroxyl group in the 6-position of the pyrido-imidazole moiety. Besides the oxidation of tthe sulfoxide function to the sulfone we could also observe the thioether (sulfide) not only of the parent compound itself but also of some of the metabolites in the series of the AR-L 115 BS-biotransformation. The identification of the human urinary metabolites, was carried out by means of TLC, HPLC, UV-, MS- and NMR-spectroscopy.
Methoxsalen, administered orally shows a strong, albeit saturable first-pass effect, as demonstrated by classical dose linearity testing and by a new method, using stable isotopes and gas chromatographic mass spectrometric analysis. The therapeutic consequences of the first-pass effect are discussed.
8-Methoxypsoralen is metabolized rapidly and completely in man. Most of the metabolites presently known have their origin in a metabolic attack on the furan moiety yielding an aryl-diol and aryl-acetic-acid and are excreted as conjugates.
A sensitive and specific colorimetric assay for paracetamol (acetaminophen) in plasma is described. After a selective column extraction (Extrelut) and hydrolysis, paracetamol is determined by the (modified) Axelrod and Brodie procedure. The whole processing is performed in a centrifuge tube. This method yields a high recovery (90%), saves time and only 1 ml of plasma is needed. Due to low blank values, the limit of detection is as low as 0.2 microgram/ml. At a concentration of 10 and 2 microgram/ml the coefficient of variation is 4% and 10%, respectively. In contrast to the often used extraction method, no emulsions are formed with this column procedure. One person is able to perform 50 analysis per day.
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8-MOP plasma levels of psoriatic patients poorly responsive to PUVA treatment (PUVA problem cases) (N = 14) and of psoriatic patients with adequate response to photochemotherapy (N = 7) were measured for 8 h after oral ingestion of 0.6-0.8 mg/kg body weight, using a gas chromatographic method. We investigated whether there are any differences in the course of the plasma kinetics between the two groups. Problem patients showed significantly lower 8-MOP plasma levels than the control group. Furthermore, the 8-MOP plasma levels increased more rapidly in the control group than in these problem patients. Deviations in time of the maximum 8-MOP plasma levels from the expected 2 h peak could be observed in 50% of the problem cases compared to only 14% of the control patients. There is no correlation between the dose and the 8-MOP plasma level achieved in the two groups, i.e. higher doses do not result in high levels. In individual cases there is not always a correlation between the plasma maximum of 8-MOP at the time of UV-A irradiation and the response to treatment. Adjustment of the UV-A irradiation to coincide with the maximum plasma levels led to an improvement in therapeutic results for three problem patients.
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Based on favour and clinical observations we have undertaken to observe the effect of vaccination against staphylococcic infection in the mouse. A standard amount of staphylococcus was used together with a metal implant. After two weeks in the control group always an infection could be observed, and germs could be cultivated. In the groups with staphypan and in the groups with vaccinated specific vaccinia a less strong infection was observed, while a vaccinia made from salmonella typhimurium and diphtheria-toxoid showed the strongest effect. The use of unspecific vaccinia deserves further attention in relation to operations which can be made after vaccination of the patient.
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Following oral administration of 14C labelled 8-methoxypsoralen (8-MOP) in man the plasma level course, the metabolite-patterns and the elimination of the parent compound and its metabolites have been investigated. Additionally the results discovered have been compared with the data of pharmacokinetics on dog and rat. In man and rat the plasma protein binding of 8-MOP has been determined. Maximal levels of the total radioactivity in the plasma were achieved 2 h after dosing. At this time 8-MOP represents 50% of the radioactivity in the plasma. The plasma protein binding in vitro of 14C 8-MOP valued from 88% to 91% in man, and between 75% and 83% in the rat. Urinary elimination of the total radioactivity as a measure of the extent of absorption varies greatly and depends on the therapeutic formulation being employed. Following the administration of the solution 74% is recovered within 48 h. Faecal elimination of the total radioactivity reached 14% within 3 days. The metabolite-pattern does not show the unchanged 14C 8-MOP. Several polar metabolites occur in the urine among which biochemical conjugates have been recognized. Only polar metabolites are observable in the faeces from which the radioactivity is incompletely extractable. From a comparison of the metabolite profiles, the rat as well as the dog seem to be a useful animal species for experimental investigations with 8-MOP.
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The HPLC (high-performance liquid chromatography) is applicable for all biochemical analyses, because of the wide variety of separation principles (adsorption-, partition-, ion-exchange- and steric exclusion-chromatography). Of exceptional importance is the reversed phase technique, a special case of partition chromatography. The sensitivity of detectors depends upon the structure of the respective substance, but is ordinarily lower -- apart from fluorescence detection -- than GLC-detectors. The development of new systems is going on. The HPLC is used in the quantitative determination of plasma levels of drugs and their metabolites. This is of special importance during the development of new drugs and for monitoring therapy. The measurement of concentrations of certain biogenic substances helps in diagnosis. An important field of application of HPLC is the use in sample clean-up for other analytical methods. In this application HPLC surpasses all other chromatographic techniques by fastness, reproducibility and suitability for automation.
Report on the perinatal mortality of 258 twin pregnancies at the department of obstetrics and gynecology of the University of Zürich, Switzerland from 1966 to 1976. The perinatal mortality of the twin deliveries was 11.6% compared to a general perinatal mortality of 2.9%. The perinatal mortality of second twins was 14.0% compared to 9.3% for the first twin. The high incidence of abnormal presentations and operative deliveries of the second twin is discussed. The incidence of prematurity under 37 weeks gestation was 48.4%. About 70% of the perinatal mortality in twins was due to prematurity with pulmonary causes leading in 44.5% of the deaths. The difficulties in the recognition of intra-uterine growth retardation in twin pregnancies is discussed.
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In 16 cases from a total of 36 (44%) the external cephalic version was successful. 18 times the relaxation of the uterus was performed by general anaesthesia with a successrate of 50% and 17 times by Fenoterol with a successrate of 35%. A V-para had a successful external cephalic version without any relaxation of the uterus. In average the external cephalic version was performed in the 39th week of pregnancy. From these 16, in whose case an external cephalic version was successful, there were 6 caesarian deliveries because of fetal indication. From 5 of these 6 caesarian deliveries it was discovered at the time of delivery a complication of the umbilicus. In one case of two massive fetomaternal transfusion the child died. In both cases of fetomaternal transfusion the placenta was located to the anterior wall of the uterus. Therefore we think this location of the placenta is a contraindiction for external cephalic version.
460 cases of threatened abortion were divided into 3 different treatment categories. Group A was treated with a combined antihistamine and antispasmodic, and Group B with tranquilizers and synthetic gestagens. Group C consisted of patients who refused therapy. The percentage of delayed abortions in group A was 79.3%, in group B 84.7% and in group C 54.8%. According to the x2-test, the difference between the treated and untreated groups is statistically significant. The mode of action of the prescribed drugs is substantiated and their effectiveness was compared with published data on other therapies. Complications of pregnancy, at delivery and during the puerperium were not more prevalent than in normal pregnancies. However, the percentage of premature births (22.9%) and of perinatal mortality (5.4%) was strikingly high. Accordingly, successfully treated threatened abortions are to be followed up as "risk" pregnancies and closely supervised as such. It is especially important to avoid a premature birth. The frequency of congenital defects and functional disturbances was 11.9%; their existence is independent of the type of therapy. Since the defects are usually of minor consequence and reversible, we advocate treatment of the threatened abortion.
A primipara with breech presentation underwent external cephalic version under tocolysis 9 days before term. The placenta was located on the anterior uterine wall. During the version, a massive feto-maternal transfusion occurred and the baby ultimately died.