Clinicians in management. Tempting clinicians across the divide.
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Career Mobility↗
Biomedical subjects
J Williams
Publications and source records attributed to J Williams.
Micro-vacuolation in rat brains after long term administration of GABA-transaminase inhibitors. Comparison of effects of ethanolamine-O-sulphate and vigabatrin.
Two "suicide" inhibitors of GABA-aminotransferase which are known to raise the concentration of GABA in vivo and to have anti-convulsant properties, have been compared for the extent to which they produce micro-vacuoles in the brains of rats. The compounds gamma-vinyl-GABA (Vigabatrin) and ethanolamine-O-sulphate were administered orally for six months to rats at doses that produced the same increase in brain GABA levels. Micro-vacuolation was found to be present in the brains of animals treated with either compound but to be more severe in those treated with Vigabatrin. A quantitative assessment using computerised image analysis revealed that both the number of vacuoles, and the area occupied by them, was twice as high in the Vigabatrin treated animals as in those treated with ethanolamine-O-sulphate. This quantitative difference could be seen to be due to the fact that in the Vigabatrin treated animals the vacuoles extended into the white matter tracts between the cerebellar folia whereas in those animals treated with ethanolamine-O-sulphate it was confined to the roof nucleus.
4-Aminobutyrate Transaminase↗
Maternal cell contamination in cultured chorionic villi: comparison of chromosome Q-polymorphisms derived from villi, fetal skin, and maternal lymphocytes.
Maternal cell contamination of chorionic villi (CV) samples used for first trimester prenatal diagnosis can cause obvious and/or unrecognized diagnostic dilemmas. The purpose of this investigation is to assess the frequency of maternal cell contamination (MCC) in chorionic villus samples and to evaluate selected parameters which might predict where contamination is more likely to have occurred. Maternal lymphocytes, chorionic villi from ultrasonically directed transcervical catheter aspiration, and fetal tissue were obtained at 8-11 weeks gestation from 45 patients undergoing elective termination. Quinacrine (Q) banded metaphases were compared from duplicate direct preparations of chorionic villi; cultured chorionic villi, fetal fibroblast tissue cultures, and maternal lymphocyte cultures. Q-polymorphisms in metaphase chromosomes were 100 per cent concordant between fetal tissue and direct CV preparation. However, evidence for maternal cell contamination occurred in 13.1 per cent of cultured chorionic villi preparations where polymorphisms were found to be identical between maternal and cultured CV and both distinct from fetal tissue preparations. Where MCC was identified, it was noted that CV cell cultivation interval was prolonged (24.2 +/- 6.8 days) compared with non-contaminated cultures (14.1 +/- 4.4 days) (p less than 0.05). We conclude that maternal cell contamination is a significant problem with chorionic villus sampling. Where direct preparations are not employed or when cultures are 'slow growing', MCC may be a significant and unrecognized complication re: fetal diagnosis. Direct preparations, multiple cultures, quinacrine banding, and maternal Q-polymorphism comparisons can minimize diagnostic dilemmas secondary to maternal cell contamination.(ABSTRACT TRUNCATED AT 250 WORDS)
Cells, Cultured↗
Iliocaval compression syndrome.
Iliocaval compression syndrome is a significant disorder in a number of patients who have lower extremity venous complaints. The diagnosis may be suspected by positive findings on exercise strain gauge venous plethysmography and unilaterally increased ambulatory venous pressures. The diagnosis is confirmed by ascending and, in some instances, descending venography which demonstrates the iliocaval compression with or without intraluminal web formation. Transstenosis pressure gradients may be measured to confirm the hemodynamic significance of the lesion. We advocate direct operative repair of the iliocaval junction with rerouting of the iliac artery and excision of the iliocaval webs with cephalic vein patch angioplasty. It provided good results in the present study when coupled with an adjunctive regimen of perioperative subcutaneous heparin and warfarin. Further investigation into the exact prevalence and significance of the iliocaval compression syndrome is needed. Only an aggressive approach to patients with lower extremity venous complaints will help clarify the exact prevalence and natural history of this disorder.
Adult↗
Multiple effects of the 72-kDa, adenovirus-specified DNA binding protein on the efficiency of cellular transformation.
The early region 2A gene (E2A) of adenovirus types 2 and 5 encodes a 72-kDa DNA binding protein (DBP) which contains two physical domains comprising approximately the amino-terminal one-third and carboxyl-terminal two-thirds of the protein, respectively. Previous work has shown that some Ad5 mutants containing temperature-sensitive (ts) mutations in the carboxyl-terminal domain of DBP, such as Ad5ts125, show a 3- to 8-fold enhanced ability to transform rat cells. We have examined the transformation characteristics of a series of Ad5 E2A deletion mutants, Ad5dl801-5, which encode either no functional DBP or encode truncated, defective DBPs. The E2A deletion mutants transformed rat embryo cells at frequencies similar to wild-type (wt) Ad5. These results suggest that the high transformation phenotype of carboxyl-terminal E2A mutants like Ad5ts125 is not due to the simple inactivation of DBP function, but rather results from an activity possessed by an altered DBP. This hypothesis is supported by the fact that the transformation phenotype of Adsts125 and similar mutants is dominant over the wild-type phenotype. A number of additional Ad2 and Ad5 E2A mutants were examined with respect to their ability to transform primary rat embryo cells. It was found that a carboxyl-terminal E2A mutant, Ad2+ND1ts23, also showed the enhanced transformation phenotype. In contrast, several amino-terminal E2A host-range (hr) mutants, originally isolated on the basis of their ability to replicate in monkey cells, transformed rat embryo cells at a frequency similar to wild-type virus. Ad2ts400, and E2A mutant with alterations in both DBP domains, showed a wild-type frequency of transformation, while two similar mutants, Ad5ts125 X 405 and Ad5ts125 X 404, showed an enhanced frequency. Last, it was found that coinfection of primary rat embryo cells with the hr mutants plus Ad5ts125 or Ad2+ND1ts23 resulted in a wild-type frequency of transformation, demonstrating that the hr mutants are dominant to the ts mutants with regard to transformation phenotype. Thus, DBP can both positively and negatively affect viral transformation in this system.
Adenovirus Early Proteins↗
Isodicentric X chromosome in a patient with myelodysplastic syndrome.
We report a further case of isodicentric X chromosome in a 65-year-old patient with refractory anemia with excess blasts in leukemic transformation. The features of this are compared with other cases reported in the literature.
Anemia, Refractory, with Excess of Blasts↗
Early third-trimester ultrasound screening in gestational diabetes to determine the risk of macrosomia and labor dystocia at term.
The purpose of this study was to determine whether an early third-trimester fetal abdominal circumference measurement can be used in patients with gestational diabetes to predict the presence or absence of macrosomia and labor dystocia at term. The predictive accuracy of a 30- to 33-week abdominal circumference measurement was tested, using the ninetieth percentile as the discriminant point. The study consisted of 201 patients with gestational diabetes who maintained weekly fasting glucose levels less than 100 mg/dl and 2-hour postprandial glucose levels less than 120 mg/dl with dietary management alone. The predictive accuracy of a 30- to 33-week fetal abdominal circumference measurement was 96.4% for ruling out macrosomia and 56.3% for predicting macrosomia. Patients with fetal abdominal circumference measurements greater than the ninetieth percentile at 30 to 33 weeks had a significantly increased incidence of cesarean section for failure to progress, shoulder dystocia, and birth trauma, whereas patients with abdominal circumference measurements less than or equal to the ninetieth percentile were at no greater risk than the general population. These results suggest that patients with non-insulin-dependent gestational diabetes with fetal abdominal circumference measurements less than or equal to the ninetieth percentile at 30 to 33 weeks are not at increased risk for macrosomia, cesarean section, or birth trauma at term, as long as their weekly glucose testing remains within normal limits. Efforts to decrease the incidence of macrosomia and its attendant risks should focus on those gestational diabetic patients whose fetal abdominal circumference greater than the ninetieth percentile at 30 to 33 weeks.
Adult↗
Chorionic villus sampling is associated with normal fetal growth.
Seventy-eight singleton term neonates, delivered of women who were 35 years of age or older after chorionic villus sampling at 9 to 11 weeks' gestation, were compared with 1335 singleton control neonates delivered at term of mothers 35 years of age or older before the clinical application of chorionic villus sampling at our institution. No statistically significant differences were found in birth weight, crown-heel length, or ponderal index between control neonates and neonates delivered after chorionic villus sampling. The sample sizes necessary to detect a 5% difference in population means at an alpha error level of 0.05 and beta error level of 0.1 were calculated for the measured variables and achieved before analysis. This study suggests that patients undergoing chorionic villus sampling are not at increased risk for the development of decreased fetal growth or intrauterine growth retardation.
Adult↗
Studies on the measurement and pharmacodynamics of human follicle-stimulating hormone.
The levels of immunoreactive follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), cortisol, and estradiol (E2) have been determined in serial samples of peripheral plasma from four subjects during the continuous, subcutaneous administration of Buserelin (Hoechst [UK] Ltd., Hounslow, UK) (250 micrograms/day) and after the intramuscular injection of purified, urinary FSH (Metrodin, Serono Laboratories [UK] Ltd., Welwyn Garden City, UK) (150 IU). During Buserelin administration the geometric mean levels of FSH and LH as measured by immunoradiometric assay were reduced by 87% and 37%, respectively, when compared with the corresponding values for days 1 and 2 of the menstrual cycle. After the intramuscular injection of FSH, peak levels (from 3.4 to 6.2 IU/l) occurred in peripheral plasma between 6 and 18 hours later. The levels were significantly elevated after 72 hours (P less than 0.01, Student's paired t-test). There was no obvious effect of the drugs on the circadian rhythms of plasma PRL or cortisol, and no significant effect on the circulatory levels of LH or E2.
Adult↗
Parkinson's disease from a patient's point of view.
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Humans↗
Approaches to cloning the genes at the human blood group ABO locus.
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ABO Blood-Group System↗
Influence of food restriction and of the presence of chicks on the reproductive system of the domestic hen.
An experiment was conducted with 4 groups of hens: a control group of laying hens, a group subjected to food deprivation for 7 d, a group subjected to food deprivation for 7 d, then re-fed for 10 d and a group subjected to food deprivation for 7 d then re-fed for 10 d with two chicks per hen introduced during the last 7 d of refeeding. Food deprivation provoked the involution of the oviduct and ovarian regression, as well as a decrease in the plasma concentrations of luteinising hormone (LH) and sex steroids (progesterone, testosterone and oestradiol). After 3 d of re-feeding, there was a significant increase in the plasma concentrations of LH and steroid hormones. This phenomenon was even more marked after 10 d of re-feeding; most of the hens of the third group which were not given chicks, were at the point of lay. The presence of chicks resulted in the expression of maternal behaviour and suppressed a rapid return to laying. This was especially marked in hens showing typical maternal behaviour traits, for which the morphological and endocrine measurements indicated a decrease in the activity of the hypothalamo-hypophyseal-gonadal axis.
Animals↗
A comparison of treatments with exogenous FSH to promote folliculogenesis in patients with quiescent ovaries due to the continued administration of an LH-RH agonist.
The circulating levels of plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH) and oestradiol (E2) have been determined in three groups of three subjects during the continuous, subcutaneous administration of an LH-RH agonist (250 micrograms/day) and after the intramuscular injection of urinary FSH (group I, 150 IU daily for 8 days, total 1200 IU; group II, 300 IU on alternate days for four injections, total 1200 IU; and group III, 150 IU on alternate days for four injections, total 600 IU). The level of circulating FSH in group I rose steadily from a geometric mean of 1.11 (pre-injection) to 8.76 U/l (at day 8), while the corresponding levels in groups II and III fluctuated according to the time and dose of the injected material. Twenty-four hours after the injection the mean level of FSH in group II was significantly higher (7.31 U/l) than the corresponding value for group I (2.79 U/l) or group III (3.48 U/l). Only those subjects in group II showed a resumption of folliculogenesis (leading, mean maximum follicular diameters of 16, 13 and 14 mm, respectively) and a corresponding increase in the concentration of plasma E2 (from 22, 43 and 103 to 906, 1477 and 2362 pmol/l, respectively).
Adult↗
A comparison of subjective and objective measures of performance in a psychiatry clerkship.
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Clinical Clerkship↗
Oral phenytoin pharmacokinetics during omeprazole therapy.
1. In a double-blind crossover study 10 healthy males received either placebo or omeprazole (40 mg day-1) for 9 days, a single dose of phenytoin (300 mg) being taken on the seventh day. 2. Omeprazole significantly increased the area under the curve (0 to 72 h) of phenytoin (mean +/- s.e. mean) from 121.6 +/- 14.0 to 151.4 +/- 13.6 micrograms ml-1 h) (P less than 0.01). 3. The peak concentration, and apparent elimination half-life of phenytoin also tended to be increased though not significantly. 4. The omeprazole-phenytoin interaction observed may be clinically important because of the low therapeutic index associated with phenytoin.
Administration, Oral↗
The effect of charcoal on mefenamic acid elimination.
Mefenamic acid suppository 500 mg was administered by rectum to eight healthy adult volunteers followed by either activated charcoal 5 g orally at hourly intervals for 7 h or an equal volume of water on two separate occasions 7 days apart. Administration of charcoal did not significantly affect the pharmacokinetic variables of mefenamic acid. Thus the beneficial effects of charcoal in the treatment of mefenamic acid overdose are largely due to interference with absorption, rather than enhancement of elimination of the drug.
Adult↗
Successful management of Cushing's disease during pregnancy by transsphenoidal adenectomy.
Pregnancy in patients with Cushing's syndrome is rare. It is associated with a high fetal loss, increased frequency of preterm labour and excessive maternal morbidity. We describe a patient who became pregnant while investigations for hypertension were being done. Cushing's disease was diagnosed and the patient had transsphenoidal pituitary surgery at 22 weeks gestation. To our knowledge this is the first time this operation has been done during pregnancy for this condition. Cushing's disease was controlled, but because of worsening hypertension, she had a caesarean section at 30 weeks gestation. Subsequently her blood pressure fell and her hydrocortisone replacement therapy is being withdrawn. Her daughter is now thriving after initial problems with pneumothoraces.
Adenoma↗