Carotid Anatomy Does Not Predict the Risk of New Ischaemic Brain Lesions on Diffusion-Weighted Imaging after Carotid Artery Stenting in the ICSS-MRI Substudy.

INTRODUCTION: The International Carotid Stenting Study (ICSS, ISRCTN25337470) randomized patients with recently symptomatic carotid artery stenosis > 50% to carotid artery stenting (CAS) or endarterectomy. CAS increased the risk of new brain lesions visible on diffusion-weighted magnetic resonance imaging (DWI-MRI) more than endarterectomy in the ICSS-MRI Substudy. The predictors of new post-stenting DWI lesions were assessed in these patients. METHODS: ICSS-MRI Substudy patients allocated to CAS were studied. Baseline or pre-stenting catheter angiograms were rated to determine carotid anatomy. Baseline patient demographics and the influence of plaque length, plaque morphology, internal carotid angulation, and external or common carotid atheroma were examined in negative binomial regression models. RESULTS: A total of 115 patients (70% male, average age 70.4) were included; 50.4% had at least one new DWI-MRI-positive lesion following CAS. Independent risk factors increasing the number of new lesions were a left-sided stenosis (incidence risk ratio [IRR] 1.59, 95% CI 1.04-2.44, p = .03), age (IRR 2.10 per 10-year increase in age, 95% CI 1.61-2.74, p < .01), male sex (IRR 2.83, 95% CI 1.72-4.67, p < .01), hypertension (IRR 2.04, 95% CI 1.25-3.33, p < .01) and absence of cardiac failure (IRR 6.58, 95% CI 1.23-35.07, p = .03). None of the carotid anatomical features significantly influenced the number of post-procedure lesions. CONCLUSION: Carotid anatomy seen on pre-stenting catheter angiography did not predict of the number of ischaemic brain lesions following CAS.

Prediction of ovulation using a dipstick sensitive to urinary luteinising hormone.

Accurate prediction of ovulation is essential for patients receiving donor insemination (AID). In 9 patients, detection of the urinary luteinising hormone (LH) surge by monoclonal antibody immunospecific dipstick tests (Ovustick) for both home and laboratory use was assessed with simultaneous quantitative estimations of plasma and urinary LH. In all patients the Ovustick accurately detected within 24 hours the beginning of the plasma LH surge. This test may prove to be a useful method for ovulation prediction but further evaluation is required.

Gonadotrophin in the term placenta of the dolphin (Tursiops truncatus), the Californian sea lion (Zalophus californianus), the grey seal (Halichoerus grypus) and man.

Chorionic gonadotrophin activity in extracts of the term placenta of a dolphin, a sea lion and a grey seal was measured by its effectiveness in increasing uterine weight in the mouse and by solid-phase RIA using hCG as immunogen and labelled antigen. Bioreactive (B) gonadotrophin was found in these placentae and, compared to the human term placenta, the concentration of CG in the dolphin was higher, in the sea lion similar and in the grey seal lower. The biological activity in each species was neutralized with a rabbit anti-hCG serum. All placental extracts contained material active in the hCG immunoassay (I). The ratio B/I was significantly higher for the CG in the placental extracts of the marine mammals compared with that of the human term placenta. Results of in-vivo bioassay, RIA, electrophoretic and gel-chromatographic studies indicate structural similarities between CG in the placentae of the marine mammals and human CG.

Relationship between corpora lutea or fetal number and plasma concentrations of progesterone and testosterone in mice.

Blastocysts (1-14) were transferred unilaterally into 63 pseudopregnant mice which were killed on Day 17. Plasma progesterone concentrations were significantly (P less than 0.05) lower in animals with one fetus than in those with 2-5 or 9-14 fetuses. Plasma testosterone concentrations were correlated with fetal number in mice with 1-13 fetuses (P less than 0.001). The total placental content of chorionic gonadotrophin in 13 litters varied directly with the number in the litter (1-6), and was 1.67 +/- 0.15 ng/placenta. The number of corpora lutea per mouse was negatively correlated with mean CL volume per mouse (P less than 0.001), and the number of conceptuses was positively correlated with mean CL volume per mouse (P less than 0.001). The effect of conceptuses on the ovary was systemic. The relationship between plasma testosterone concentration and conceptus number may be due to gonadotrophins acting on the ovary, or androgens produced by the placenta or fetus.

Gonadotrophin and progesterone concentrations in placentae of grey seals (Halichoerus grypus).

Chorionic gonadotrophin (CG) measured by bioassay and progesterone by immunoassay were present in the placentae of grey seals (Halichoerus grypus) from about 20 days after implantation until parturition. During this period a small and significant decrease in the concentration and a large increase in the total amount of placental CG occurred. The biological activity of seal placental CG was neutralized with an anti-hCG serum. There was a correlation between fetal length and the total amount of progesterone in the placenta. The corpus luteum persisted throughout pregnancy and there was a significant correlation (P less than 0.001) between CL diameter and the weight of the ipsilateral ovary. Hypertrophy of fetal testes and ovaries was observed and adult gonad size was reached at about the time of parturition. We suggest that placental CG is the hormone responsible for the precocious enlargement of fetal gonads in grey seals.

An appraisal of the mouse uterine weight assay for the bioassay of chorionic gonadotrophin in the macaque term placenta.

The results obtained in this investigation have shown that the increase in uterine weight of 21-day-old mice, injected with monkey CG, was affected significantly by the number of injections made, the interval between injections and the time of autopsy after the first injection. Failure to take account of these factors may explain why some investigators, using the increase in mouse uterine weight as the index of response, do not find CG in macaque placentae after the 10th week of pregnancy. The present investigation confirmed that extracts of term placentae from rhesus and stump-tailed monkeys contained measurable amounts of CG whose biological activity could be neutralized by an anti-hCG serum.

Qualitative difference in follicle-stimulating hormone activity in the pituitaries of young women compared to that of men and elderly women.

The possible existence of qualitative differences between FSH in pituitaries from men and women of different ages was investigated with the use of an in vitro bioassay, an in vitro bioassay, and a RIA. Aqueous extracts were made from pituitaries obtained at autopsy and frozen until extracted. The FSH activities per pituitary and the ratios of FSH activities as obtained with the three assay methods were similar for young and elderly men. The ratios of in vivo biological to in vitro biological FSH activities were similar for men and postmenopausal women and significantly higher than the corresponding ratio for FSH from young women. With the in vivo bioassay the activity in the extracts of pituitaries from men and young women were similar, whereas extracts from postmenopausal women had significantly higher activity. With the in vitro bioassay the extracts from young women and elderly women had a similar content of FSH activity, whereas the FSH level in the extracts of male pituitaries was significantly lower. The results of the RIA correlated well with those of the in vitro bioassay. In conclusion, the results show that FSH in pituitaries from young women has a biological activity that is qualitatively different from FSH of men and elderly women. The relatively low in vivo biological activity of FSH from young women compared to FSH from men and elderly women was most likely due to a more rapid clearance of the hormone from the circulation of the test animal.

Subchronic effects of gum arabic (Acacia) in the rat.

Young Wistar rats were fed gum arabic (GA) at dietary concentrations of 0% (two control groups), 1, 2, 4, 8 and 20% for 13 weeks. The criteria studied were body weights, food and water consumption, urinalysis, liver and kidney weights, clinical chemistry, haematology, and histology. No untoward effects were observed at dose levels below those which caused dietary imbalance. At the top dose, female rats showed a small reduction in kidney weight, caecal enlargement, and changes in serum urea and total CO2. Male rats showed no differences from the control groups at dietary concentrations up to approx. 8%, but food and water consumption, body weight, liver and kidney weights all decreased significantly and caecal enlargement was evident at the top dose tested. There were no histological changes and no significant changes in haematological parameters in male or female rats at the top dose tested. The no-untoward effect concentrations were 8.6% (5.2 g/kg/day) and 18.1% (13.8 g/kg/day) for male and female rats respectively.

Gonadotrophic activity of the guinea-pig placenta during pregnancy.

A gonadotrophic substance was extracted from placentae and subplacentae of guinea-pigs. Biological and immunological assays of these tissues obtained on Days 10-63 of pregnancy showed the highest mean concentration of the gonadotrophin on Day 18. Extracts chromatographed on Sephadex G200 had components active in the radioimmunoassay system for hCG, hCG-alpha and hCG-beta subunits. The elution profiles of these extracts were similar to those obtained with human term placentae and purified hCG and its subunits. The guinea-pig placental extracts also cross-reacted with an antiserum to the beta subunit of ovine LH, as did hCG. The biological activity of placental and subplacental extracts and of the hCG standard as neutralized by an anti-hCG serum. There is a strong similarity between hCG and the substance extracted from guinea-pig placentae which may therefore have a luteotrophic function similar to that of hCG.

The similarity of chorionic gonadotrophin and its subunits in term placentae from man, apes, old and New World monkeys and a prosimian.

Chorionic gonadotrophin (CG) was estimated, by bioassay and radioimmunoassay (RIA), in placental extracts from 11 ape and monkey species. There was a significant correlation between the results of the two assay systems (r = 0.903, p less than 0.001). The concentration of CG in most primate term placentae was the same as that in the human placenta at term. Extracts from all placentae cross-reacted with antiserum to ovine LH-beta subunit, and those of the chimpanzee and gorilla also had a significant cross-reaction with an antiserum to the carboxyl terminal peptide of the HCG-beta subunit. Primate placentae chromatographed on Sephadex G-200 had components active in the RIA systems for HCG, HCG-alpha HCG-beta subunits. In general, the elution profiles of all ape and monkey placental extracts resemble those made from human term placentae and of purified HCG and its subunits. The shape of the elution patterns from human and non-human material suggests that there was more than one molecular form of CG-alpha subunit activity. A second, more retarded molecular form having beta subunit activity was found in extracts made from human, gorilla, gibbon and rhesus monkey placentae. The similarity between the structure of ape and monkey placental CG with HCG and its subunits implies a function similar to that of HCG in late pregnancy.

Reproductive capacity of rhesus monkeys following bilateral ovarian x-irradiation.

The effect of ovarian X-irradiation of the rhesus monkey upon menstrual cycle length, duration of menstrual bleeding, excretion of gonadotrophin in the urine, concentration of gonadotrophin in the pituitary gland, ovarian histology, and breeding performance was investigated. Doses below 4000 R had no significant effect upon the above criteria. By contrast, doses of 4000 to 7000 R rapidly induced amenorrhoea in most animals, but unexpectedly these animals did not excrete greater than normal amounts of gonadotrophin. The pituitary content of gonadotrophin in cyclic and non-cyclic animals was not significantly different. Some births occurred in the animals which had been X-irradiated.

Pregnancy diagnosis in the common marmoset (Callithrix jacchus jacchus).

Abdominal palpation of the uterus was carried out on 25 pregnant and 29 non-pregnant marmosets (Callithrix jacchus jacchus). 195 complete 24-hour urine specimens, collected between the first week of gestation and term (21 weeks), were tested with the Sub-Human Primate Tube (SHPT) test. No significant differences between the two methods in their ability to diagnose pregnancy were obtained between the first and 13th week of gestation. The SHPT test was seldom positive after the 13th week of pregnancy, whereas, with one exception, palpation always indicated pregnancy.

Absence of hCG-like activity in the blood of women fitted with intra-uterine contraceptive devices.

Blood was obtained at various stages of the menstrual cycle from 201 women fitted with intra-uterine contraceptive devices (IUDs), and plasma levels of hCG were determined by radioimmunoassay. Urine samples were obtained from 117 of these women and tested, before and after sephadex gel filtration, in a haemagglutination inhibition test for pregnancy (Pregnosticon). Plasma hCG was undetectable (less than 25 MLU/ml) in all but one of the 201 women and, in this instance, the hCG-assay appeared to be measuring a midcycle peak of LH, as evidenced by high plasma FSH levels. All unextracted urines gave negative results in the Pregnosticon test but, after extraction, 18 of the 117 urines gave positive reactions, most of these being from women at midcycle or in the luteal phase. We conclude that the IUD does not permit the development of the embryo to a point where it is capable of secreting measurable amounts of hCG. Recent claims to the contrary are probably due to cross-reaction of LH or non-specific interference in the assays used for measuring hCG.

Urinary excretion of biologically active chorionic gonadotrophin by the pregnant marmoset (Callithrix jacchus jacchus).

No significant correlation exists between the amount of biologically active marmoset chorionic gonadotrophin (mCG) in urine and results obtained with an immunological pregnancy test. The pregnant marmoset excretes large amounts of oestrogenic steroids, which must be removed, to prevent the enhancement of the response of the bioassay for mCG. More than 99% of these unconjugated and conjugated urinary oestrogens can be removed by extraction with acetone and ether. mCG is excreted throughout pregnancy, maximum levels occurring between the 8th and 9th week of gestation. There is a considerable within- and between-animal variation in the amount of mCG excreted. However, the pattern of gonadotrophin excretion by the pregnant marmoset is similar to that of man and the apes but unlike that of baboons and macaques.

Evaluation of the sub-human primate tube test for pregnancy in primates.

A haemagglutination inhibition test, developed specifically for primates, diagnoses early pregnancy in the chimpanzee, gorilla, orang-utan and baboon. The test was sensitive and reacted positively when the concentration of gonadotrophin in urine was equivalent to 0.03 i.u. human chorionic gonadotrophin per ml. This degree of sensitivity and the certitude that it cross-reacts with primate luteinizing hormone probably accounts for most of the false positive results.

The effects of large doses of the anabolic steroid, methandrostenolone, on an athlete.

Doses of the anabolic steroid, methandrostenolone, nearly ten times greater than those used therapeutically, have resulted in a marked depression of levels of testosterone in urine and blood, and in some depression of gonadotrophin excretion by a male athlete. The administration of the drug has been checked and its metabolism studied from the pattern of urinary metabolites.