Biomedical subjects
Publications and source records attributed to B L Pimstone.
An assay is available to determine the presence or absence of oestrogen receptors in breast cancer cells. The presence of oestrogen receptors predicts a 60% response rate to empirical hormonal therapy, and the absence a 10% response rate. Early evidence suggests that the additional presence of other hormone receptors in breast cancer cells will improve this response rate.
Using a previously described radioimmunoassay for growth hormone release inhibiting hormone (GH-RIH), the presence of GH-RIH-like immunoreactivity in urine has been characterized by demonstrating mobility identical to synthetic GH-RIH standard on two sephadex gel chromatographic systems, and parallelism of dilutions of the sephadex fractions with synthetic GH-RIH. Furthermore, 74% of the sephadex fraction cross-reacting in the immunoassay bound to antibody conjugated to sepharose and could be eluted by 1 M acetic acid. This immunospecific eluate showed identity with synthetic GH-RIH on both ion exchange and thin layer chromatography. Thus GH-RIH-like immunoreactivity is present in normal urine; this may have potential relevance in the search for a physiological role for this peptide.
Endocrine studies were performed on twelve patients with proven idiopathic haemochromatosis. Basal gonadotrophin levels and/or their responses to LH releasing hormone (LHRH) were low in nine patients, all of whom showed low plasma testosterone levels and clinical evidence of hypogonadism. Those patients with normal gonadotrophin responses had higher testosterone values, suggesting that the poor testosterone secretion was primarily due to inadequate trophic stimulation. No patient showed hypothyroidism of hypothalamic-pituitary origin, while the cortisol response to hypoglycaemia was normal in all six patients studied. GH responses were more variable and difficult to interpret, since the number of the patients studied was small and the degree of hypoglycaemia after insulin was unpredictable.
Two patients are described with elevation of circulating somatomedin A concentration but normal growth hormone levels. One,a young male, appeared clinically acromegalic; the other, a young female, was tall with kyphoscoliosis, and her appearance resembled Marfan's syndrome. In both patients plasma growth hormone concentration was suppressible by hyperglycaemia. It is suggested that their clinical syndromes resulted from excessive somatomedin activity.
Somatomedin (sulphation factor) activity was measured in 26 species by a porcine cartilage bioassay. Although non-dialysable inhibitory factors were present in many species, sulphation factor activity was present in the sera of all the vertebrates studied but was absent from the invertebrates.
Immunoreactive GHRIH is present in normal CSF at a level of 55 +/- 28 pg/ml. Immunoreactivity shows mobility identical to synthetic GHRIH standard on sephadex and thin layer chromatography, and can be removed by antibody conjugated to sepharose.
A case is reported in which virilization of long duration and gradual progression was found in association with ovarian hyperthecosis and bilateral hilar cell lesions. The frequency occurrence of both masculinizing and nonmasculinizing ovarian tumors in association with ovarian hyperthecosis and polycystic ovaries is discussed.
Somatostatin, a growth hormone release-inhibiting factor, isolated originally from the hypothalamus, has been shown to have widespread effects on brain and endocrine and exocrine pancreatic and gut function. Furthermore, it has a widespread distribution in the CNS, gut and C cells of the thyroid -- cells which probably migrated originally from the neural crest during development. While the pharmacological effects of somatostatin are diffuse, its physiological role is at present unknown, but in view of its concentration in synaptosomal fractions of neural tissue, it may have a neurotransmitter or a synaptic modulator function.
1. Young Wistar rats were used as an experimental model to determine the effects of protein-energy malnutrition on glucose tolerance and insulin release. 2. Malnourished rats presented some of the features commonly found in human protein-energy malnutrition, such as failure to gain weight, hypoalbuminaemia, fatty infiltration of the liver and intolerance of oral and intravenous glucose loads. 3. The rate of disappearance of glucose from the gut lumen was greater in the malnourished rats but there was no significant difference in portal blood glucose concentration between normal and malnourished rats 5 and 10 min after an oral glucose load. 4. Insulin resistance was not thought to be the cause of the glucose intolerance in the malnourished animals since these rats had a low fasting plasma insulin concentration with a normal fasting blood glucose concentration and no impairment in their hypoglycaemic response to exogenous insulin administration. Furthermore, fasting malnourished rats were unable to correct the insulin-induced hypoglycaemia despite high concentrations of hepatic glycogen. 5. Malnourished rats had lower peak plasma insulin concentrations than normal control animals after provocation with oral and intravenous glucose, intravenous tolbutamide and intravenous glucose plus aminophyllin. This was not due to a reduction in the insulin content of the pancreas or potassium deficiency. Healthy weanling rats, like the older malnourished rats, had a diminished insulin response to intravenous glucose and intravenous tolbutamide. However, their insulin response to stimulation with intravenous glucose plus aminophyllin far exceeded that of the malnourished rats. Thus the impairment of insulin release demonstrated in the malnourished rats cannot be ascribed to a 'functional immaturity' of the pancreas.
A specific antiserum has been produced to haemocyanin conjugaed synthetic growth hormone release inhibiting hormone (GHRIH). This has allowed the development of a radioimmunoassay for GHRIH sensitive to 5 pg/tube. GHRIH content in 2 m acetic acid extracts of rat tissues have been measured and show the majority to be CNS-especially hypothalamus and septum and preoptic areas with substantial amounts in spinal cord and thalamus. Extra neurological localization in pancreas, gastric antrum, colon and thyroid have been demonstrated.
Intranasal administration of gonadotropin hormone (GnRH) in doses ranging from 2-4 mg produced a consistently prolonged LH response in patients with secondary amenorrhea. In 4 cases, a delayed secondary rise occurred. A similarly prolonged FSH response was observed in the majority of patients. Six hours after intranasal GnRH, FSH and LH values were well above basal levels and were higher than those observed at a similar interval after intravenous GnRH. Plasma GnRH levels after intranasal administration failed to achieve the high peaks found after the intravenous route but maintained elevated levels for at least an hour and often longer. Despite the much lower plasma GnRH levels, intranasal GnRH produced a sustained effect on LH and FSH secretion, greater than GnRH given by the intravenous route.
Fifteen women with anorexia nervosa were studied before and after weight gain. Basal plasma thyroid stimulating hormone (TSH) and prolactin (PRL), and the responses of both these hormones to thyrotropin releasing hormone (TRH), were normal. Basal plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) were low in patients who were emaciated, and their responses to gonadotropin releasing hormone (GnRH) were impaired. Both basal and stimulated levels of LH and FSH rose with weight gain, with a linear correlation between gonadotropin levels and body weight expressed as a percentage of standard. The FSH response became greater than normal in patients who had regained weight to more than 70% of standard, while the LH response to GnRH was exaggerated in those who had regained weight to more than 80%. Basal plasma estradiol (E2) levels were low at first, but returned to within the normal range in patients over 80% of standard. Menstruation resumed in some patients after they had regained weight. The relationship between body weight and gonadotropin levels appears to be an important feature of the menstrual disturbance in anorexia nervosa. The restoration of a normal body weight is a prerequisite for the resumption of menstruation in this condition, but other as yet unidentified factors may also be involved.
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The effects of somatostatin (growth hormone release inhibiting hormone) on basal gastrin were studied in patients suffering from pernicious anaemia and chronic renal and liver disease, and during sequential arginine/insulin-stimulated gastrin release in normal subjects. When basal gastrin concentrations were normal (10-50 pg/ml) in controls and in patients who were in renal and liver failure, somatostatin had no effect on gastrin levels. Raised basal gastrin levels in pernicious anaemia and in 2 cases of chronic renal disease, were significantly inhibited by somatostatin with a half-life (T 1/2) of 3-4 minutes. Arginine infusion caused an insignificant rise in serum gastrin which was unaffected by somatostatin, whereas insulin hypoglycaemia significantly stimulated gastrin release, which was inhibited by somatostatin.
Early insulin release after oral glucose is absent in protein-calorie malnutrition (PCM). There is an increase of the insulin-glucose ratio at 10 and 15 min induced by potassium supplementation compared to a similar group receiving an identical diet without supplementary potassium. This suggests that impaired insulin secretion in PMC is in part due to a potassium mediated disturbance of insulin release.
In view of the previously reported inverse correlation between the elevated serum growth hormone (HGH) and low alanine in children with protein-calorie malnutrition (PCM), 30-min alanine infusions were performed in five children with PCM and 12-hr infusions in four children before and after therapy. These infusions did not lower basal HGH or improve its glucose suppressibility in untreated PCM, excluding a feedback relationship between HGH and alanine. There was no insulinotropic effect during 30-min infusions, but an improved insulin response to glucose after the 12-hr alanine infusion was found in three of four children before therapy. Plasma glucose rose slightly during alanine infusion in three of five children before treatment, but the magnitude of change was small and the relevance unclear.
Diseases of the endocrine glands may be silent or of little apparent consequence for long periods of time, but may nevertheless have an unexpected and acutely fatal termination. Some of these facets are explored in this paper. A full clinical history (including therapy) and thorough autopsy is necessary to exclude the endocrine causes of unexpected deaths.
The serum immunoreactive insulin (IRI) concentrations, and glucose dissappearance rate-constants after intravenous glucose administration were measured on admission and during recovery in children suffering from protein-energy malnutrition (PEM). 2. A high potassium intake resulted in a considerable increase in the serum IRI levels early in the treatment period. There was a definite relationship between potassium depletion and many measurements of insulin secretion. 3. The results are consistent with the hypothesis that impaired insulin release in children suffering from PEM is partly the result of potassium depletion.