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Biomedical subjects

M Davies

Publications and source records attributed to M Davies.

At least 433 records · Page 24Linked to original sources

Vitamin D metabolism in patients intoxicated with ergocalciferol.

Vitamin D metabolites were measured on admission in eight patients intoxicated with ergocalciferol (serum calcium 3.01-4.05 mmol/l) and also during the subsequent 2 months in six of the eight. Serum concentrations of 25-hydroxyergocalciferol, on admission, were grossly elevated in all patients (range 583-1843 nmol/l). Serum calcium concentration was related significantly only to the concentration of 25-hydroxyergocalciferol (P = 0.003). Concentrations of 25-hydroxyergocalciferol in serum were significantly related to those of calciferol (P = 0.004). Elevated initial concentrations of 1,25-dihydroxycalciferol, mainly as 1,25-dihydroxyergocalciferol, were found in seven of the eight patients (range 179-313 pmol/l). It is suggested that the hypercalcaemia in these patients may be explained by the action of 25-hydroxyergocalciferol at high concentration in competing for 1,25-dihydroxycalciferol receptors, thus exerting a biological effect per se, and also by increasing the synthesis of 1,25-dihydroxycalciferol through a mass-action effect on the renal 1 alpha-hydroxylase.

25-Hydroxyvitamin D 2↗

Vitamin D prophylaxis in the elderly: a simple effective method suitable for large populations.

A comparison of two regimens of vitamin D prophylaxis in elderly institutionalized subjects has been made. Sixty-six subjects received 2.5mg vitamin D2 by mouth in December 1982; a further group of 62 received the same dose in December 1982 and again in June 1983. Blood samples have been analysed for 25-hydroxyvitamin D2 [25(OH)D2] in 10 subjects from each group over a 12-month period. The serum 25(OH)D2 was maintained at normal concentrations for most of the year in the once-a-year dosage group but at the end of 12 months only 60% were fully protected. The twice-per-year regimen offered complete protection maintaining the serum 25(OH)D2 above the threshold associated with osteomalacia. It is concluded that a twice-yearly regimen of vitamin D supplementation is a practical method for prophylaxis in institutionalized elderly people.

25-Hydroxyvitamin D 2↗

Phaeochromocytoma: a review of the St Vincent's Hospital, Melbourne experience (1969-84) and of recent advances in management.

Phaeochromocytoma is an unusual tumour which is eminently curable by surgical means. It is difficult to diagnose clinically because it mimics other illnesses. The clinical features of 13 cases of phaeochromocytoma diagnosed at St Vincent's Hospital, Melbourne, between 1969 and 1984 are briefly described. This review emphasizes the several major improvements in both diagnostic and localizing tests which have occurred over the 16 year period of the series. These include the clonidine suppression test and plasma and urine catecholamine estimations in diagnosis and techniques such as CT scanning and the I131-meta-iodobenzyl-guanidine scan used for localization of the tumour. Careful pre-operative preparation, based on adequate alpha blockade and intra-operative monitoring, is essential for the safe and successful removal of the tumour, which was eventually accomplished for all 12 cases in which removal was attempted. However, the most important step in the diagnosis and treatment of phaeochromocytoma is the initial consideration of the diagnosis. This step depends on the level of awareness of the disorder amongst clinicians.

Adrenal Gland Neoplasms↗

Three tests of cortisol secretion in adult endogenous depressives.

Seventy-nine drug-free adult patients fitting RDC criteria for major depressive disorder endogenous subtype (EMDD), and 64 normal adult volunteers, were studied at pretreatment with at least one of three tests of cortisol secretion. The tests were: 1) Mean half-hourly cortisol concentrations from 1 p.m. to 4 p.m. (1-4 PM CORT); 2) plasma cortisol response to 0.15 mg/kg of dextroamphetamine hydrochloride (DACT) in the afternoon; 3) dexamethasone suppression test (DST) using 1 or 2 mg. Thirty-six depressive and 27 volunteers underwent all three tests. Analysis of the data was performed for each test singly, for all pairs of tests and for all three tests in same subjects. Results show that the single most sensitive cortisol test for depressions is the DACT (72%), with a specificity of 88%. These tests may measure different underlying pathophysiologies associated with depression.

Adolescent↗

Pregnancy-associated nonspecific immunosuppression: kinetics of the generation and identification of the active factors.

The effect of gestational age and maternal parity on the development of nonspecific immunosuppressive activity in the sera of pregnant women, which inhibited the in vitro transformation of unrelated lymphocytes by phytohemagglutinin, was examined. Quantitative demonstration of this activity was dependent, in part, on the source of the lymphocytes and on the serum concentration in culture. The immunosuppressive activity became evident as the pregnancy progressed, and in late-pregnancy sera it was mediated by two factors, immunosuppressive factors (ISF) I and II with apparent Mr of 2 X 10(6) and 150,000 daltons. By analysis and comparison of different types of sera fractionated by gel filtration on Sephacryl S-300, it was evident that ISF-I and ISF-II were also present in male and nulliparous nonpregnant female sera, but in inactive forms. Hence the immunosuppressive factors did not appear to be "produced" in pregnancy, but the observed activity was a reflection of the "activation" of preexisting molecules in the serum. An accompanying report (Am J Reprod Immunol Microbiol. 1985; 9:84-90) describes the regulation of the activation event.

Adult↗

Pregnancy-associated nonspecific immunosuppression: mechanism for the activation of the immunosuppressive factors.

The nonspecific immunosuppressive effect observed in pregnancy sera and mediated by two factors, immunosuppressive factors (ISF) I and II, was regulated by a third molecule termed the pregnancy-depleted immunoregulatory factor (pdIRF). Natural depletion of serum pdIRF levels during pregnancy resulted in the activation of the ISF-I and ISF-II molecules, which prior to conception existed in the serum in inactive forms. The inactive ISF-I and ISF-II molecules in male sera and in nulliparous nonpregnant female sera can be activated following the artificial selective depletion of pdIRF by absorption onto Sephacryl S-300. It is proposed that inactive complexes consisting of the ISF-I and ISF-II molecules and pdIRF and possibly involving Ca2+ and Mg2+ ions are a feature of normal sera. The pdIRF molecule has an apparent Mr of 100,000-125,000 daltons and consists of a single major polypeptide of 63,000 daltons. Equal concentrations of pdIRF are present in male and female normal sera.

Calcium↗

The partial characterisation of maternal anti-trophoblast antibody responses generated during normal human pregnancy.

The anti-trophoblast antibody response generated during a normal human pregnancy and detected by a recently developed enzyme-linked immunosorbent assay, was partially characterised in terms of maternal influences, nature of the antibodies and nature of the antigenic determinants present on the syncytiotrophoblast plasma membrane. The level and incidence of the response was significantly affected by maternal parity, while the maternal ABO, but not Rhesus, blood group antigens exerted a minor influence. The antibody response was predominantly mediated by IgG molecules of the IgG1,2 and 4 subclasses. The IgG molecules existed in the maternal sera either in the form of 'free' molecules or were involved in immune complexes. The antibodies interacted with determinants that were present on all the placental membranes tested and hence are possibly organ specific. The antigenic specificities were absent from erythrocytes and peripheral blood lymphocytes.

Antibodies↗

Antigenic analysis of immune complexes formed in normal human pregnancy.

Immune complexes, isolated from pregnancy sera by absorption to immobilized protein A, were dissociated and the antigen components separated from the IgG antibodies, which possessed immune reactivity directed against the plasma membrane of the syncytiotrophoblast layer of the placenta. Gel filtration studies demonstrated that five separate antigens could be identified and were of placental origin, as observed by their reactivity in an ELISA with affinity purified anti-trophoblast antibodies isolated from maternal sera. The five antigens of apparent mol. wt 2 X 10(6), 400,000, 150,000, 13,000 and less than 10,000 daltons were designated maternally recognised trophoblast antigens (MRTA), numbers V-IX; the relative proportions of these antigens in the sera were 14%, 68%, 16%, 0.5% and 1%, respectively. Immune complexes were also identified in nulliparous non-pregnant female sera and consisted of the 150,000 and the less than 10,000 daltons antigen components. The relationship between the MRTA present in the immune complexes and the MRTA (numbers I-IV) previously identified as components of the trophoblast plasma membrane is discussed.

Antigen-Antibody Complex↗

Effect of ascorbic acid on plasma calcium in guinea pigs.

Ascorbic acid (246 mg/kg body weight/day) was administered orally to 9-week old female guinea pigs of the Hartley strain over a period of 20 months. The controls received 40 mg/kg body weight/day of ascorbic acid in the diet. Observations were made on body weight, food and water consumption, plasma ascorbic acid, and the total calcium and ionic calcium levels at various times during the growth of these animals. A second experiment was carried out when the guinea pigs were 18 months old. In addition to the oral intake, they received intraperitoneally 623 mg/kg body weight/day of sodium ascorbate for 6 weeks. With this treatment, the ascorbic acid intake for the test animals was 20 times that for the controls. The plasma ascorbic acid and calcium levels of these animals were measured during the treatment. In the ascorbic acid-treated animals, there was a significant elevation in plasma ascorbic acid level in comparison with the controls, but no substantial differences were observed in the body weight, total calcium or ionic calcium levels in the plasma. The results suggest that the administration of large quantities of ascorbic acid does not affect total calcium or ionic calcium levels in the plasma of these animals.

Animals↗

Growth hormone secretion in prepubertal children with major depression. I. Final report on response to insulin-induced hypoglycemia during a depressive episode.

Insulin tolerance tests (ITTs) were carried out on 46 drug-free prepubertal children with severe emotional disorders. Thirteen met unmodified Research Diagnostic Criteria for major depressive disorder, definite endogenous subtype, 17 met the criteria for nonendogenous major depressive disorder, and 16 fit DSM-III criteria for nondepressed neurotic disorders. The group with endogenous depression had significant hyposecretion of growth hormone (GH) in this test when compared with the other groups. Since GH hyposecretion in response to ITT has been found in most studies to be associated with endogenous major depression in adults, the data support the validity of the diagnosis of prepubertal endogenous major depressive disorder and the hypothesis of similarity or identity of prepubertal and adult major depressive disorders.

Affective Symptoms↗

Growth hormone secretion in prepubertal children with major depression. II. Sleep-related plasma concentrations during a depressive episode.

Plasma growth hormone (GH) concentrations were determined every 20 minutes during sleep in 71 prepubertal children: 22 had endogenous major depressive disorder, 20 had nonendogenous major depressive disorder, 21 had nondepressed neurotic disorders, and eight were normal. Both depressive groups secreted significantly more GH during sleep than did controls. Measures included maximal GH plasma peak and area under the curve (AUC) during the total sleep period, during the first three hours after sleep onset, and during the first five hours after sleep onset. An AUC cutoff of 2,000 ng X min/mL identified positively half the prepubertal children with major depression; with a specificity of 78% (v neurotics) and 100% (v normal children). Increased GH secretion during sleep may be a marker of illness, a past episode, or trait for prepubertal major depression regardless of endogenicity.

Affective Symptoms↗

Growth hormone secretion in prepubertal children with major depression. III. Response to insulin-induced hypoglycemia after recovery from a depressive episode and in a drug-free state.

Insulin tolerance tests (ITTs) were performed after at least four months of sustained recovery from an episode of a major depressive disorder in 18 drug-free prepubertal children. Eleven had a definite endogenous subtype; seven did not. Sixteen children with nondepressed neurotic disorders made up a control group. The children with past endogenous depression continued to have significant hyposecretion of growth hormone (GH) in this test when compared with the other groups. Illness-recovery correlations were highly significant for the major depressive group as a whole. Paired comparisons of both depressive groups were not significantly different from illness to recovery. We conclude that prepubertal children with endogenous major depression continue to have hyposecretion of GH in response to ITTs in a recovered state and that this neuroendocrine marker is state independent. A GH hyporesponse to ITT may be a true marker of a past episode or of trait for endogenous major depressive disorder in prepuberty.

Affective Symptoms↗

Growth hormone secretion in prepubertal children with major depression. IV. Sleep-related plasma concentrations in a drug-free, fully recovered clinical state.

Prepubertal children with major depressive disorder have shown increased growth hormone (GH) secretion during sleep while in a depressive episode. When restudied in a fully recovered state (for at least three months) and drug free (for at least one month), their increased GH secretory pattern during sleep had not changed. Illness-recovery correlations using area under the curve for GH secretion during sleep were highly significant, whereas paired comparisons showed no significant differences. In addition, children who had recovered from major depressive episodes secreted significantly more GH during sleep than did nondepressed neurotic and normal children. No significant differences in delta-sleep were found in the depressed group between ill and recovered states nor among those who had recovered from major depressive episodes or controls. It is concluded that increased GH secretion during sleep is independent of depressive episodes, remains unaltered after full recovery, and may be a true marker of trait for major depressive disorder in prepuberty.

Affective Symptoms↗

Dystrophic calcification, cataracts, and enamel hypoplasia due to long-standing, privational vitamin D deficiency.

A 19-year-old Indian girl presenting with intermittent tetany, enamel hypoplasia, bilateral cataracts, and calcification of the basal ganglia is described. Dental evidence suggested a calcification defect had been present from the age of 2-3 years. Hypocalcemia, hyperphosphatemia, and low levels of immunoassayable parathyroid hormone (iPTH), urinary cAMP, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were documented, suggesting hypoparathyroidism with vitamin D deficiency. A bone biopsy showed osteomalacia. Following ultraviolet irradiation and oral calciferol therapy, a symptomatic and biochemical response typical of privational vitamin D deficiency occurred. iPTH levels rose to normal and remained normal following withdrawal of treatment, indicating that the clinical features were entirely due to long-standing vitamin D deficiency.

Adult↗