Long-term retention of estradiol by brain cell nuclei and female rat sexual behavior.
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Biomedical subjects
Publications and source records attributed to J M Gray.
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Profound hypokalemia was observed in 73 patients in a major university teaching hospital during a three-year period. When compared with hospitalized subjects used as controls, these patients experienced a greater mortality, were substantially more likely to be female, but were not more likely to suffer from cardiovascular disease. Use of a diuretic appeared to precipitate profound hypokalemia infrequently, and when it did, the clinical situation was extremely complex. Over 10% of the patients with hypokalemia had acute myeloid leukemia, an incidence 22 times greater than that expected. Hypokalemia should be sought in all patients with this disease, since it is an avoidable cause of death. Further studies into the mechanism of hypokalemia are required to explain its striking preponderance in women.
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1 A double-blind randomized trial to compare the relative efficacy of the 1,5-benzodiazepine, clobazam, the 1,4-benzodiazepine nitrazepam, and placebo as hypnotics was carried out. 2 A preference technique was used and the analyses were performed sequentially. 3. The results confirmed that nitrazepam was superior to placebo as a hypnotic but failed to show that clobazam was superior to either placebo or nitrazepam in a ratio of 2:1. Thus, it seems likely that the hypnotic properties of clobazam are minimal. 4 Clobazam is not suitable for use as a hypnotic in hospitalized patients.
Ovarian hormones, particularly 17 beta-estradiol, have important effects on body fat levels in rats, but it is not known whether 17 beta-estradiol can act directly on various fat depots to affect adiposity or whether these effects are entirely indirect (e.g. via food intake, exercise, or various metabolic actions). We have found high affinity, estrogen-specific macromolecular binding of 17 beta-[3H]estradiol in the cytoplasmic fraction of adipose tissues from ovariectomized rats. Saturation analysis indicates a Kd of 7.4 X 10(-10) M, and binding is inhibited by unlabeled 17 beta-estradiol or 11 beta-methoxy-17-ethynyl-1,3,5(10)-triene-3,17beta-diol (R2858) but not by progesterone, 5 alpha-dihydrotestosterone, or cortisol. 17 beta-[3H]Estradiol binding is virtually abolished by incubation with pronase but not with DNase or RNase, indicating that the binding macromolecule is probably a protein. Binding is seen in all adipose tissues studied, including abdominal, sc, and brown fat. Binding site concentration is highest in parametrial fat pads, followed by retroperitoneal, brown, omental, and inguinal depots. Binding is also seen in the cytoplasmic fraction of isolated parametrial adipocytes. These data indicate that the various adipose tissues might be estrogen target tissues in rats. Therefore, it is possible that estrogenic effects on body weight and composition could be mediated in part by direct estrogen action on adipose tissues.
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As part of a drug surveillance programme details of nuclide administration were recorded for 5288 consecutive patients admitted to the medical wards of a large general hospital. Overall use of nuclides amongst this group was found to be low, and multiple exposure to radiation as a result of nuclide administration is not a major hazard when compared to the diagnostic information provided.
A 48-year-old woman had severe symptomatic thrombocytopenia three times in 13 months. Each episode followed ingestion of iopanoic acid. The interval between drug ingestion and onset of symptoms was 40, 12, and 8 hours. Resolution to normal platelet counts occurred in 6, 5, and 8 days. The third thrombocytopenic crisis occurred while the patient was receiving maintenance steroid therapy, given because the initial diagnosis was idiopathic thrombocytopenic purpura. Incubation of platelet-rich plasma with the patient's serum caused platelet lysis if either the patient or the donor serum obtained after ingestion of iopanoic acid was present in the mixture.
A patient is described in whom there was strong circumstantial evidence of an interaction between warfarin and co-trimaxazole. To test the validity of this hypothesis a series of in vitro and in vivo human studies were untaken. The results indicate that interaction may occur in which the sulphamethoxazole moiety of co-trimoxazole displaces warfarin from its binding sites on plasma albumin. Nevertheless, this interaction occurs only at high plasma levels of warfarin and is most likely to be clinically significant only in patients receiving high doses of warfarin who have low plasma albumin concentrations. These studies indicate that the use of co-trimoxazole is not contra-indicated in patients receiving warfarin therapy, but care should be exercised, especially in patients with high plasma warfarin:albumin ratios.
Data from a hospital-based drug surveillance programme were used to determine how often benzodiazepine drugs were used in general medical wards. Benzodiazepines were the drugs most commonly used as hypnotics and were given to 32% of these patients. Concomitant use of more than one benzodiazepine drug or of benzodiazepines with other psychoactive drugs was common and often irrational. A series of double-blind patient-preference studies comparing various benzodiazepines and a benzodiazepine with an antihistamine showed that for short-term hypnotic effect there were no differences between three common benzodiazepines but elderly patients preferred benzodiazepines to the antihistamine, which produced more undesired effects. These results suggest that currently diazepam is the hypnotic of choice for medical ward inpatients.
Plasma, blood cell, and total body potassium levels were measured serially in 21 patients receiving long-term diuretics for the treatment of cardiac oedema and the results compared with similar measurements in 10 control subjects. Initially, all diuretic recipients received potassium chloride supplements. However, in 17 of the 21 subjects these were discontinued and measurements of potassium status were repeated regularly thereafter. No significant fall in the measured indicators of potassium status were observed in the patients in whom potassium was withdrawn; however, in one subject with persistent cardiac failure who presented with hypokalaemia this was not corrected even after intensive potassium supplementation. It is concluded that for those taking a normal diet who are free of any major gastro-intestinal disorder, routine potassium supplementation is unnecessary, and might indeed occasionally prove harmful.