A multicentre trial of perhexiline maleate in the treatment of angina pectoris.
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Biomedical subjects
Publications and source records attributed to G Weiss.
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Two methods for the preparation of carbon black aerosols have been investigated: incomplete combustion of acetylene, acetylene + benzene and other hydrocarbons as well as a "resublimation" of amorphous carbon. The first method was developed for generating soot aerosols in animal experiments, but the latter method needs more basic investigation. Using radioactive acetylene and benzene the produced soot aerosol could be labelled by 14C. Benzo(a)pyrene aerosol was prepared by means of a vapour condensation and was also radioactive labelled. With a combination of both generators, a combined carbon black and benzo(a)pyrene aerosol was prepared. The benzo(a)pyrene amounts bound to the soot were in the range of from 1 ng to 50 microgram per 1 mg soot. Experiments dealing with adsorption and desorbtion of benzo(a)pyrene on soot in the gas phase have shown, that benzo(a)pyrene is relatively tightly adsorbed and cannot be easily or completely desorbed.
A 31-year-old patient with incomplete testicular feminization syndrome characterized by a 46, XY karyotype in a phenotypic female with absent müllerian structures, marked clitoromegaly, testes and wolffian duct structures, partial labioscrotal fold fusion, and male levels of circulating androgens is described. She was challenged with estradiol benzoate (EB) to simulate the preovulatory surge of estradiol seen in cycling women. This EB challenge resulted in a negative feedback response for FSH but an LH surge similar to that induced with EB in cycling women. This suggests that in the incomplete testicular feminization syndrome there is hypothalamic or pituitary resistance to the blocking effects of androgens on LH surge production.
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Plasma samples from peripheral and ovarian veins were obtains from women at cesarean section. A peptide that immunologically cross-reacts with a specific antiserum to porcine relaxin is present in all samples. Its concentration is four times higher in the ovarian vein draining the ovary, which contains the corpus luteum of pregnancy, than in either the peripheral vein or the contralateral ovarian vein. Secretion of ovarian relaxin correlates with secretion of ovarian progesterone, thus providing another index of luteal function.
Thirty-five individuals aged 17 to 24 in whom severe chronic hyperactivity had been diagnosed 10 years before were studied together with 25 matched controls. There were no significant differences in mean height or weight or in electroencephalographic findings, but the mean pulse rate was significantly higher in the hyperactive group. Cognitive style tests indicated continued difficulty in reflection (resulting in more errors) but less impulsivity (longer reaction time) in the hyperactive individuals. Compared with controls, hyperactive subjects were continuing to have more scholastic difficulty, although this difference seemed to be less pronounced than 5 years before. Their adjustment in work situations and living arrangements did not differ significantly from that of the controls. Restlessness, both reported and observed, continued to be a problem for the hyperactive individuals, and socialization skills and sense of well-being continued to be poorer than in the controls. The hyperactive individuals did not show significantly more antisocial behaviour, nonmedical use of drugs or serious psychiatric disturbances.
A short term in vitro test for granulocyte chalone activity eas examined for its specificity and reliability. The test used the inhibition, by granulocyte extracts, of 3H-thymidine (3H-Tdr) uptake in to the acid-insoluble material by rat bone marrow cells in vitro to measure possible chalone activity. Among the many possible 3H-Tdr artifacts pool size dilution by Tdr contained in the extracts was excluded using an E. coli mutant requiring thymine. Several amino acids and biogenic amines do not affect the test. However, continuous and pulse labelling of bone marrow cells with 3H-Tdr, viability tests and micro flow fluorometric measurements of the cell cycle distribution following colcemid treatment strongly suggests that the cells do not proliferate in vitro during short term incubation, since practically no cells enter the S-phase, cells in the S-phase die and few if any cells proceed through G2 and mitosis. Moreover, the test cannot exclude cytotoxicity. Thus, the in vitro test may only sceem for an unspecific S-phase inhibitor and must hence be supplemented by another assay to prove the chalone nature of an extract or fraction. The test per se fails to meet most of the requirements of a valid granulocyte chalone assay.
The method proposed by the Federal Department of Health for the determination of aflatoxin B1,B2,G1, and G2 was tested for additional determination of aflatoxin M1. With relatively small changes of the original method, all aflatoxins including. B1, B2,G1,g2, and M1 can be determined quantitatively in milk, milk powder, butter, cheese, quark, cream, yoghurt and fruit yoghurt.
Several starting materials and procedures for the extraction and purification of granulocyte chalone activities were tested and evaluated. Among others, leuko-adhesion of bovine blood granulocytes on nylon and cotton wool and direct extraction with polar organic solvents were found suitable. Following PVP-leukapheresis ascites fluids were collected from rats, purified by ultrafiltration and Sephadex G 25 chromatography to yield 2 inhibitors at Ve/Vo = 2.1 and 2.6 and one stimulator at 2.0 by the in vitro 3H-thymidine test. Fraction 2.1, which has met the criteria of a granulocyte chalone by the diffusion chamber and agar colony test, was found thermostabile and to contain several peptides. Yet evidence for the peptide nature of the inhibitor is not conclusive. Extracts from bovine blood granulocytes contained only the inhibitor at 2.1. Problems related to the in vitro test for chalone activity were discussed.
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The existence of a 17-deoxylation pathway in the metabolism of cortisol has been established by isolation of two 17-deoxy metabolites of cortisol. They have been identified as the 20alpha and 20beta-hydroxy isomers of 3alpha,20-dihydroxy, 11-oxo-5beta-pregnan-21-oic acids by comparison of the nuclear magnetic resonance spectra (nmr) and high resolution mass spectra of their methyl esters with authentic samples and confirmed by reverse isotope dilution.
The time courses of serum concentrations of prolactin, estradiol, estrone, progesterone, LH, and FSH were studied in seven pregnant rhesus monkeys from 1 month prior to delivery until 1 month after parturition. All animals nursed their young. Circulating levels of estradiol and estrone increased during the last few days of pregnancy, reaching peak values of 700 pg/ml and 350 pg/ml, respectively, on the day prior to delivery, fell precipitously to about 25 pg/ml within 1 day after parturition, and remained at this level for at least 30 days. Serum prolactin concentrations also increased during the week preceding parturition, rose abruptly at delivery, and then declined gradually. Serum progesterone levels ranged between 2 and 3 ng/ml during the last month of pregnancy, rose slightly a few days prior to parturition, decreased sharply at delivery to 50% of prepartum levels and declined gradually thereafter. Serum LH and FSH levels were not detectable during the entire sampling period. The administration of estradiol benzoate to two pregnant monkeys at midgestation, in a manner which replicated the normal prepartum increase in serum estradiol concentrations, failed to elicit an elevation in circulating prolactin levels or to induce premature delivery of the fetus.
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Intramuscular injection of 6.6 mg of estradiol benzoate (EB) in oil was used in 34 women as a test of the ability of the pituitary-hypothalamic axis to produce a gonadotropin surge (positive-feedback response). These responses were compared to Clomid responses. All of the normal cycling women, two-thirds of oligo-ovulatory but menstruating women, and one-third of amenorrheic women had LH surges to EB challenge. Estradiol benzoate is a more specific test of positive feedback response than Clomid. It also may be effective in inducing ovulation in some amenorrheic patients refractory to Clomid treatment.
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SUMMARY: Three groups of hyperactive children were compared by various measures of outcome 5 years after initial evaluation: 24 who were treated with methylphenidate for 3 to 5 years during the follow-up period, 22 treated with chlorpromazine for 18 months to 5 years, and 20 who had received no medication during the follow-up period. The three groups were matched with respect to age, IQ, socioeconomic class and sex. No statistically significant differences were found between the three groups on the following measures of outcome: emotional adjustment, delinquency, Wechsler Intelligence Scale for Children, Bender Gestalt visual-motor test and academic performance (as measured by number of grades failed). Initially there was a significant difference between the three groups on ratings of hyperactivity and family diagnosis. Hyperactivity scores decreased significantly over the 5 years; family diagnosis ratings changed little. Analysis of covariance for these two measures showed no difference in degree of improvement between the three groups. Our impression was that methylphenidate was helpful in making hyperactive children more manageable at home and at school, but did not significantly affect their outcome after 5 years of treatment.
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A radioimmunoassay for serum unconjugated estriol in the menstrual cycle with a sensitivity of about 5 pg/ml is described. 8 cycles were studied. In 2 cycles, single spikes of 22 and 30 pg/ml were obtained. In 3 cycles, concentrations of 4-5 pg/ml were found whereas in the other 3 studies, no estriol was detected. In general, peaks of estriol corresponded to peaks in estradiol plus estrone. Patients in 4-12 weeks of gestation were also studied. Concentrations as high as 262 pg/ml were found but in isolated instances, no estriol was detected. The results support the view that in contrast to the pregnant state, in the normal menstrual cycle, the bulk of the estriol produced is conjugated before release into the blood.