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Biomedical subjects

B M Davies

Publications and source records attributed to B M Davies.

At least 19 recordsLinked to original sources
PubMed2004

Spinal cord plasticity in response to unilateral inhibition of the rat motor cortex during development: changes to gene expression, muscle afferents and the ipsilateral corticospinal projection.

In developing Wistar albino rats, ventral horn muscle afferent boutons are lost following corticospinal innervation. Motor cortex lesions rescue a proportion of these boutons and perturb activity dependent expression of cJun and parvalbumin (PV) in the spinal cord. Therefore, we tested whether activity-dependent competition between corticospinal and proprioreceptive afferents determines the balance of these inputs to motor output pathways by delivering the inhibitory GABA agonist muscimol unilaterally to the forelimb motor cortex using slow release polymer implants from postnatal day 7 (P7) coincident with corticospinal synaptogenesis. Controls received saline. Inhibition of immature cortical neurons by muscimol was confirmed with separate in vitro electrophysiological recordings. After P28, spinal cord sections were immunostained for PV, cJun and muscle afferents transganglionically labelled with cholera toxin-B (CTB). Unilateral inhibition reduced contralaterally the number of PV positive spinal cord neurons and muscle afferent boutons in the dorsolateral ventral horn, compared to controls, and significantly altered the distribution of motoneuronal cJun expression. Separately, descending tracts were retrogradely traced with CTB from the cervical hemicord contralateral to implants. Forelimb sensorimotor cortex sections were immunostained for either CTB or PV. In muscimol treated animals, significantly fewer neurons expressed PV in the inhibited hemicortex, but as many CTB labelled corticospinal neurons were present as in controls, along with an equally large corticospinal projection from contralateral to the implant, significantly greater than in controls. Unexpectedly, unilateral inhibition of the motor cortical input did not lead to an expanded muscle afferent input. Instead, this was reduced coincident with development of a bilateral corticospinal innervation.

Age Factors↗
PubMed1991

Plasma cortisol and 11-deoxycortisol activity in depressed patients and normal volunteers.

Plasma cortisol and 11-deoxycortisol were measured in 30 depressed patients and 110 normal volunteers before and after a 1.0 mg dexamethasone suppression test (DST). Post-dexamethasone plasma cortisol, 11-deoxycortisol and the cortisol/11-deoxycortisol ratio were significantly higher in the depressives compared to the controls, even when age and sex were taken into account. Pre-dexamethasone plasma cortisol, post-dexamethasone cortisol, 11-deoxycortisol and their ratio were significantly higher in the cortisol nonsuppressors than in the suppressors. The measurement of post-dexamethasone 11-deoxycortisol and the ratio did not differentiate between endogenous and reactive depression. Using the normative data, we explored several methods for determining a criterion value to define abnormal post-dexamethasone plasma 11-deoxycortisol and the cortisol/11-deoxycortisol ratio in depressed patients. All showed poor sensitivity and a low positive predictive value for depression. The measurement of 11-deoxycortisol thus does not enhance the clinical utility of the DST.

Adult↗
PubMed1991

Radiation induction of drug resistance in RIF-1: correlation of tumor and cell culture results.

The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and etoposide (VP16). The frequency of these drug-resistant cells is increased after irradiation. The frequency of drug-resistant cells and the magnitude of radiation-induced drug resistance are different in cell culture than in tumors. The dose-response and expression time relationships for radiation induction of drug resistance observed in RIF-1 tumors are unusual. We hypothesize that at high radiation doses in vivo, we are selecting for cells that are both drug resistant and radiation resistant due to microenvironmental factors, whereas at low radiation doses in vivo and all radiation doses in vitro, we are observing true mutants. These studies indicate that there can be significant differences in drug-resistance frequencies between tumors and their cell lines of origin, and that radiation induction of drug resistance depends significantly on whether the induction is done in tumors or in cell culture. These results imply that theories about the induction of drug resistance that are based on cell culture studies may be inapplicable to the induction of drug resistance in tumors.

Animals↗
PubMed1990

Dexamethasone kinetics in depressed patients before and after clinical response.

Dexamethasone pharmacokinetics were measured in 19 depressed patients, 10 dexamethasone suppression test (DST) nonsuppressors and nine suppressors, following a 1 mg oral dose in tablet form at 2300 h. Median dexamethasone concentrations were significantly lower in the nonsuppressors from 3-16 hr post-administration. Nonsuppressors had a significantly lower area under the curve than suppressors, and plasma clearance was significantly faster in the nonsuppressors than in the suppressors. Eleven patients, six nonsuppressors and five suppressors, agreed to a repeat DST after clinical improvement when all six nonsuppressors had normal DST responses. There were no significant differences between the median dexamethasone concentrations, or any of the pharmacokinetic parameters measured, of the "normalising" nonsuppressors and the suppressors. Dexamethasone kinetics were altered in depressed nonsuppressors but became normal with remission of depressive symptoms and normalisation of the DST response.

Adult↗
PubMed1990

Drug resistance following irradiation of RIF-1 tumors: influence of the interval between irradiation and drug treatment.

RIF-1 tumors contain a small number of cells (1 to 100 per 10(6) cells) that are resistant to 5-fluorouracil, methotrexate, or adriamycin. The frequency of drug-resistant cells among individual untreated tumors is highly variable. Radiation, delivered in vivo at doses of 3 to 12 Gy, increases the frequency of methotrexate- and 5-fluorouracil-resistant cells, but not the frequency of adriamycin-resistant cells. The magnitude of induction of 5-fluorouracil and methotrexate resistance shows a complex dependence on the radiation dose and on the interval between irradiation and assessment of drug resistance. For a dose of 3 Gy, induced 5-fluorouracil and methotrexate resistance is seen only after an interval of 5 to 7 days, whereas for a dose of 12 Gy, high levels of induced resistance are observed 1 to 3 days after irradiation. The maximum absolute risk for induction of resistance is 4 per 10(4) cells per Gy for methotrexate, and 3 per 10(6) cells per Gy for 5-fluorouracil. These results indicate that tumor hypoxia may play a role in the increased levels of drug resistance seen after irradiation, and that both genetic and environmental factors may influence radiation-induction of drug resistance. These studies provide essential data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be caused by radiation-induced drug resistance.

Animals↗
PubMed1990

Heterogeneity of adverse hepatic reactions to tetrahydroaminoacridine.

Of 14 patients taking tetrahydroaminoacridine (THA) for the trial treatment of Alzheimer's disease, five developed mildly abnormal liver function tests. Four asymptomatic patients with persistently abnormal serum transaminase levels underwent liver biopsy, in order to determine the nature of the hepatic lesions. One subject had granulomatous hepatitis while three showed focal, predominantly centrilobular, liver cell necrosis and mild fatty change. One of the latter showed both tissue and peripheral blood eosinophilia. The liver function tests of the fifth patient, who was symptomatic, became normal after reduction of the dose of THA so he did not undergo biopsy. These findings suggest that the pathogenic mechanisms for THA-induced liver injury are heterogeneous ranging from hypersensitivity reactions to direct injury, and including combinations of the two. Patients receiving THA for treatment of Alzheimer's disease need regular monitoring of liver function.

Aged↗
PubMed1990

The dexamethasone suppression test in anorexia nervosa. The influence of weight, depression, adrenocorticotrophic hormone and dexamethasone.

When 20 female anorexic in-patients were investigated with weekly DSTs, 10 had an abnormal result at initial testing. There was no identifiable relationship between severity of weight loss and DST status; % ideal body weight was no different between suppressors and non-suppressors. There was no consistent relationship between normalisation of the DST response and weight gain. Depressive symptoms were common, with half the patients scoring 20 or more on the HRSD. Plasma ACTH concentrations before and after the DST were normal. There was a significant negative correlation between plasma dexamethasone concentrations and pre- and post-dexamethasone plasma cortisol concentrations.

Adrenocorticotropic Hormone↗
PubMed1990

Psychiatry as a career choice.

The paper reviews articles in the field of research in medical education specifically dealing with the factors involved in the choice of Psychiatry as a medical specialty and describes three studies conducted in Melbourne. These studies focus on the relevance of personality factors in the psychiatrist's choice of a career. While they confirm other work in this field, it is felt that the emphasis should no longer be placed on single factors. Future investigations should be multifactorial in design and analysis to highlight the combination of factors underlying such choices.

Adult↗
PubMed1988

The dexamethasone suppression test and plasma dexamethasone in generalized anxiety disorder.

A Dexamethasone Suppression Test nonsuppression rate of 27% was found in a group of 30 generalized anxiety disorder patients before treatment. The dexamethasone concentrations in the eight nonsuppressors were significantly lower than in eight suppressors matched by sex and age, but were similar to those in five nonsuppressors from a matched normal control group. The dexamethasone concentrations in the generalized anxiety disorder suppressors and a matched group of eight normal control suppressors were similar. After successful nondrug behavioral treatment, all generalized anxiety disorder patients were suppressors. Posttreatment dexamethasone concentrations in the initial nonsuppressor patients remained significantly lower than in the initial suppressors. The results suggest that low plasma dexamethasone concentrations after 1 mg oral dexamethasone may confer a vulnerability to nonsuppression that may be expressed in the presence of high state anxiety.

Adult↗
PubMed1988

The dexamethasone suppression test: a study in a normal population.

One hundred healthy, non-depressed volunteers were given a standard dexamethasone suppression test (DST) to determine the appropriate criterion values of plasma cortisol to define suppression or nonsuppression. By radioimmunoassay (RIA) of cortisol, the criterion value for 5% nonsuppression was plasma cortisol greater than 187 nmol/l, and for suppression less than 153 nmol/l, with an indeterminate range between these values. Use of the widely accepted pre-determined criterion value of 138 nmol/l gave a significantly greater frequency of nonsuppression. Values of cortisol measured by two RIAs in a subset of 43 volunteers were not equivalent. With the experimentally determined criterion value, no significant differences between nonsuppressors and suppressors were found for any measured physical or psychological parameters. Women taking oral contraceptives had significantly higher plasma cortisol pre-dexamethasone and post-dexamethasone. Their exclusion did not alter the calculated criterion value for the remainder, but their separately estimated criterion value was significantly higher. Caution should be exercised when classifying the DST status of women on oral contraceptives, particularly when values are at the lower end of the nonsuppressor range. Determination of a separate normal range for them may be warranted.

Adrenocorticotropic Hormone↗
PubMed1987

Tyramine pressor response with moclobemide--a reversible monoamine oxidase inhibitor.

Moclobemide is a reversible, short-acting monoamine oxidase inhibitor (MAO1), specific for MAO A. To study moclobemide effects on the tyramine pressor response, we gave 12 depressed patients (2 males, 10 females; mean age 47, SD 11 years) an i.v. tyramine test after 7 days drug free. The mean (+/- SD) tyramine dose to raise systolic blood pressure 30 mmHg was 5.6 +/- 2.5 mg. Repeat tyramine testing after 2 weeks of treatment with moclobemide (280 +/- 90 mg/d) showed the tyramine dose required was reduced to 2.5 +/- 1.6 mg (n = 8). The mean (+/- SD) increase in sensitivity to tyramine was 2.9 +/- 1.8. Four patients did not have repeated tyramine tests as testing was discontinued because of tyramine-induced cardiac arrhythmias. Moclobemide seems an effective antidepressant with less tyramine sensitivity than MAOIs in current use.

Adult↗
PubMed1986

The effects of weight change on the dexamethasone suppression test in depressed and anorexic patients.

Prior studies on weight change and hypothalamic-pituitary-adrenal (HPA) axis functioning are reviewed. Data on 58 depressed and eight anorexic patients is presented. No significant difference in the frequency of cortisol non-suppression in the dexamethasone suppression test (DST) was found between depressed patients with a history of weight loss and those without, nor between depressed patients who lost weight during their first week in hospital and those who did not. Mean weight loss of suppressors did not significantly differ from that of non-suppressors. Of 12 patients whose DST normalised during their stay in hospital, only four gained weight. Five anorexics who were non-suppressors were less than 70% of their ideal body weight (IBW), while three suppressor anorexics were greater than or equal to 70% IBW. These results indicate that mild to moderate weight change is not a significant influence on DST response in depression.

Anorexia Nervosa↗
PubMed1985

Antidepressant therapy: benefits and risks in perspective.

The introduction of second generation antidepressants, such as mianserin and nomifensine, was prompted by the desire to produce drugs which were safer, had fewer side-effects and were faster acting than the tricyclics. A brief review of the data on mianserin and nomifensine is presented in relation to these aims. Some advantages for the new drugs can be claimed and the risks of severe adverse effects relating to blood dyscrasias in the case of mianserin, and fever in the case of nomifensine, appear outweighed by the therapeutic gains.

Cardiovascular Diseases↗
PubMed1983

Zimelidine: a placebo-controlled trial in depression.

Twenty-eight hospital inpatients with a primary major depressive disorder were treated with either zimelidine or placebo. Patients were matched for age, sex, and initial severity of depression and assigned double blind to the treatment regimen. An initial dosage of 150 mg/day was used for up to 6 weeks. Zimelidine was significantly more effective in alleviating the symptoms of depression than placebo, with 82% of zimelidine and 25% of placebo patients showing clinical improvement. There were few complaints of severe side effects in zimelidine-treated patients, and few effects on the cardiovascular system. Two zimelidine-treated patients were withdrawn for suspected drug-related adverse events. Zimelidine was a safe, effective antidepressant in this group of patients.

Adolescent↗
PubMed1982

A clinico-pathological study of lithium nephrotoxicity.

Lithium salts, well recognised as acute nephrotoxins, have recently been implicated in the development of a chronic focal interstitial nephropathy. As part of a clinico-pathological study of lithium nephrotoxicity, renal function and renal histology has been compared between 25 patient on maintenance lithium therapy and 19 patients with affective illnesses prior to commencement of lithium therapy. Significant evidence of chronic renal damage was present in biopsies of lithium treated patients when compared with cadaveric donor kidneys (p less than 0.001). Similar damage was noted in biopsies from patient prior to lithium and differed from donor kidneys (p less than 0.01). The degree of damage was not significantly different between the patients on lithium and those not yet on lithium. An acute specific tubular lesion was note in patients on lithium, and a marked degree of distal tubule dilation and microcyst formation were also observed. Significant defects in urinary concentrating ability and urinary acidification were present in patients on lithium and there was a correlation between the degree of these defects and the duration of lithium therapy. There was no evidence of a substantial reduction in glomerular filtration rate, which could be ascribed to the lithium therapy.

Adult↗