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Biomedical subjects

M Wilkinson

Publications and source records attributed to M Wilkinson.

At least 289 records · Page 16Linked to original sources

Repeated convulsions induce pseudopregnancy in the intact rat and inhibit steroid-mediated gonadotrophin secretion in the ovariectomized rat.

We have investigated the effects of repeated flurothyl-induced seizures on reproductive function in the female rat. This treatment rapidly induced a state of pseudopregnancy in intact cyclic rats. Prolactin is clearly implicated in this response since treatment with bromocriptine readily counteracted the influence of the convulsions. The mechanism of action of repeated seizures was further characterized in experiments on ovariectomized rats. Thus, 11 daily convulsions, but not a single acute seizure, were able to inhibit the positive feedback effect of progesterone on LH and FSH release in oestrogen-primed animals. In this model also the pituitary gland response to gonadotrophin releasing hormone in vitro was significantly reduced. However, the convulsions had no effect on basal serum or basal in-vitro secretion of LH and FSH in ovariectomized or oestrogen-treated ovariectomized rats. Thus, repeated seizures modified the hypothalamo-pituitary axis in such a way as to prevent it from responding to stimulation. Our results indicate that normal reproductive function in the female rat is very sensitive to repeated seizures and suggest that similar effects may be evident in women subjected to electroconvulsive shock therapy. The successful use of bromocriptine in reversing the influence of seizures in the rat suggests its use in man also.

Animals↗

Function of the future respiratory system in the growth retarded fetal sheep.

The development of the future air breathing respiratory system was investigated in eight carunclectomised fetal sheep and five control fetal animals over the last third of gestation (approximately day 100-day 145). Carunclectomy resulted in the test fetal animals being hypoxaemic, hypercapnic, hypoglycaemic and acidotic. All fetal animals were chronically instrumented with diaphragmatic electromyographic leads, fetal jugular vein and carotid artery catheters, an amniotic fluid catheter and small electrocardiographic leads placed on the chest wall. There was evidence of a significant, but small, reduced relative lung size in the carunclectomised animals by day 140 without corresponding relative changes in the weight of the brain, liver, or heart. Diaphragmatic electromyograph (EMG) was analysed in detail over the last third of gestation. In both groups of animals, the normal reduction in fetal 'breathing' rate, and the normal increase in fetal apnoea was noted with increasing periods of diaphragmatic silence as fetal apnoea was noted with increasing periods of diaphragmatic silence as gestation advanced. Linear regression analyses revealed that fetal breathing rate was significantly reduced over the last third of gestation, whilst fetal apnoea significantly increased in the carunclectomised animals. Average total integrated diaphragmatic activity was reduced prior to 120 days. This reduction was evident in the strength of each diaphragmatic contraction before 110 days. In three test and three control animals, histochemical analyses were undertaken to fibre type the muscles of the diaphragm. Fatigue resistant fibres were significantly reduced in the carunclectomised fetuses, and fibre diameters were diminished. Centroid analyses of the power spectrum of the diaphragmatic EMG did not however support the concept of increased muscle fatigue in the test animals.

Animals↗

Hyperparathyroidism: experiences with treated and untreated patients.

During a seven-year period, after the introduction of parathyroid hormone assays, 113 patients with primary hyperparathyroidism were seen at an Australian teaching hospital. In 68, parathyroidectomy was followed by normalization of serum calcium levels. Fifteen patients (six referred from other units) remained hypercalcaemic after their initial neck exploration. Thirty patients with biochemical changes indicative of primary hyperparathyroidism were not referred for surgery, mainly because of old age or lack of symptoms. Those patients who were not submitted to surgery, and those who had undergone unsuccessful neck explorations, were observed (while hypercalcaemic) for a mean period of three years. During the period of observation, no deterioration occurred in the clinical or biochemical status of these patients. It is proposed that patients with non-symptomatic primary hyperparathyroidism may be managed by clinical observation, rather than by immediate parathyroidectomy.

Adult↗

Circadian surges of LH in the ovariectomised rat occur coincident with enhanced pituitary responsiveness to GnRH.

Experiments are described in which we have investigated the responsiveness to GnRH of pituitary glands obtained from ovariectomised rats in which LH surges were induced by steroid priming (a) by estrogen implants and (b) by estrogen-progesterone injections. These treatments generate LH surges late in the light phase. Stimulation with GnRH in vitro revealed a large increase in responsiveness coincident with the surge of LH. We suggest that this effect is mediated through a self-priming effect of GnRH and that this in vitro technique may be used to detect hypothalamic release of GnRH.

Animals↗

Transpubertal modulation of pituitary and testicular function in the ob/ob mouse.

We have investigated developmental, transpubertal, changes in the responsiveness to stimulation of pituitary gland and testes from the male ob/ob mouse. These organs were removed from ob/ob mice at 33 and 90 days after birth and stimulated with GnRH and LH, respectively, in vitro. Pituitary glands from lean mice released significantly more LH than those from ob/ob mice at both ages. In contrast, FSH release was higher in young ob/ob mice but not significantly different at 90 days when compared with lean controls. LH-stimulated testes revealed that although the young ob/ob testes released significantly less testosterone (T) than lean controls, the response became normal after the time of expected puberty. The production of 5 alpha-androstane-3 alpha, 17 beta-diol (DIOL), although reduced at both ages in ob/ob mice, declined transpubertally in both lean and ob/ob mice. As a result, the ratio of T:DIOL which normally becomes much greater than 1 with the advent of puberty, also increases to greater than 1 in the ob/ob males, suggesting that sexual maturation of testicular androgen biosynthesis is approximately normal. We conclude that the differences in pituitary and testicular response to stimulation could arise from a defect in the ability of the pituitary gland to release gonadotrophins.

Androstane-3,17-diol↗

Development of a quotidian increase in pituitary responsiveness to GnRH in prepubertal female rats.

Pituitaries from immature male and female rats (5, 13, 21, 27 and 30 days of age) were removed at 08:00 or 16:00 h and stimulated with GnRH in vitro. In female rats more LH was released from pituitaries taken at 16:00 h than at 08:00 h on Days 21, 27 and 30, but not on Days 5 and 13. There were no differences in male rats in responsiveness of pituitaries taken at these two times. The ability of GnRH to induce release of more LH in the late afternoon may help to synchronize hormone output to coincide with first ovulation.

Animals↗

Vitamin D metabolites and their relationship to azotaemic osteodystrophy.

Bone biopsies were performed and serum concentrations of vitamin D metabolites were measured in twenty-four patients with chronic renal failure. The concentrations of three metabolites--25-dihydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D (24,25-OH2D) and 1,25-dihydroxyvitamin D (1,25-OH2D)--were significantly lower in uraemic than in normal sera. There was a positive correlation between serum 24,25-OH2D and serum 25-OHD, whereas serum 1,25-OH2D values, which were independent of those of the other vitamin D metabolites, were negatively correlated with serum creatinine and serum inorganic phosphate. The two major skeletal lesions, osteomalacia and parathyroid osteopathy, while coexisting in many patients, varied independently in relation to their severity and were correlated with different vitamin D metabolites. The severity of osteomalacia was negatively correlated with the serum concentrations of 25-OHD and 24,25-OH2D while th severity of parathyroid osteopathy was negatively correlated with serum 1,25-OH2D values. To our knowledge these are the first systematic studies correlating skeletal histology with dihydroxylated vitamin D metabolites in renal failure in man.

Bone and Bones↗

An unexpected increase in pituitary sensitivity to gonadotrophin releasing hormone after treatment with porcine follicular fluid (inhibin) in immature hemicastrate rats.

Porcine follicular fluid (PFF) contains a factor (inhibin or folliculostatin) which is reported to selectively inhibit the secretion of follicle-stimulating hormone (FSH) from the anterior pituitary gland. Chronic treatment of hemicastrate immature rats with PFF is able to partially inhibit the FSH-mediated hypertrophy of the remaining testis. However, the pituitaries from PFF-treated rats are paradoxically very sensitive to stimulation with gonadotrophin-releasing hormone (GnRH) and secrete significantly more FSH than control glands. Furthermore, this increased sensitivity results in a large increase in luteinizing hormone (LH) secretion. These observations suggest that under certain circumstances PFF is not selective for FSH and that it surprisingly stimulates rather than inhibits gonadotrophin secretion.

Animals↗

Post-traumatic headache.

The incidence of post-traumatic headache varies widely in different series. This paper presents a group of 84 patients aged between 11 and 38 years who had had severe head injuries. All had been unconscious for at least 24 hours and the majority (85%) for over a week. Only 12% had headaches. The incidence of headaches was lower in the more severely injured of the patients as judged by the extent of the physical disabilities and length of unconsciousness, though it was higher in those with severe mental changes. The reasons for the low incidence of headaches in this series are discussed.

Adolescent↗

Some factors determining prognosis in young people with severe head injuries.

Eighty-four patients under the age of 40 were rehabilitated after severe head injuries. All had been unconscious for at least 24 hours, and 35 were unconscious for more than four weeks. The mean length of treatment was 30.2 weeks. Seventy were discharged home, 13 remained in hospital, and one died. Seventy-two of the patients were followed up nine months to 15 years after the injury. Twenty-eight were working, 27 were at home but not working, 13 were in hospital, and four were dead. Prolonged unconsciousness, extensive neurological damage, and severe mental changes were found to be the main factors adversely affecting the prognosis; an inadequate family background and cerebral hypoxia were also considered to have an influence.

Accidents, Traffic↗