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Biomedical subjects

M Davies

Publications and source records attributed to M Davies.

At least 379 records · Page 21Linked to original sources
PubMed1988

The petrous temporal bone and deafness in X-linked hypophosphataemic osteomalacia.

Radiological anatomy of the petrous bones and skull base has been studied in a group of 11 patients with X-linked hypophosphataemic osteomalacia and hearing loss, and comparison made with a control group of normal subjects. Patients with X-linked hypophosphataemic osteomalacia were found to have generalised osteosclerosis and thickening of the petrous bone, with some narrowing of the internal auditory meatus, particularly in its mid-portion. No evidence of platybasia nor of basilar impression was found in the hypophosphataemmic group. The aetiology of the hearing loss which occurs in patients with X-linked hypophosphataemic osteomalacia is discussed in relation to the radiological abnormalities described.

Chromosomes↗
PubMed1988

The effect of dialysate on peritoneal phagocyte oxidative metabolism.

The respiratory and oxidative responses of human peritoneal polymorphonuclear leukocytes (PMN) and peritoneal macrophages (PM phi) following exposure to unused continuous ambulatory peritoneal dialysis fluid (CAPD) and early dwell effluent were studied using an open oxygen (O2) electrode system and by measurement of oxygen radical-derived luminol-dependent chemiluminescence. Both cell types responded to stimulation by increasing O2 consumption and by generating chemiluminescence even at external O2 concentrations below 50 microM O2. Oxygen concentrations in the dialysate, as measured by blood gas analysis, were never lower than 118 +/- 8.3 microM O2 even during active peritonitis. Thus oxygen availability does not appear to be rate limiting for phagocyte oxidative metabolism in the peritoneal cavity. Preexposure of both inflammatory cell types to unused fluid or early dwell CAPD effluent significantly reduced both stimulated oxygen uptake and the subsequent ability of these cells to generate chemiluminescence without significantly affecting their viability. Further investigation of this down regulatory phenomenon using unused fluid and laboratory prepared dialysis fluid revealed that low pH (5.3) and high sodium lactate concentration in combination are directly responsible for the suppressive effect of unused fluid and early dwell effluent on cell function. These observations demonstrate that cellular host defense may be impaired early in the dialysis cycle as a result of lactate mediated "stunning" of resident phagocytes. The precise nature of the molecular species responsible for this suppressive effect remains to be identified.

Dialysis Solutions↗
PubMed1988

Evidence for depressant 5-HT1-like receptors on rat brainstem neurones.

1. The technique of microiontophoresis was used to evaluate the contribution of 5-HT1-like, 5-HT2- and 5-HT3-receptors to the depressant effects of 5-hydroxytryptamine (5-HT) on neurones in the midline of the medullary brainstem of the rat in vivo. 2. Depressant responses to 5-HT were resistant to antagonism by the 5-HT2-receptor antagonist ketanserin and the 5-HT3-receptor antagonist MDL 72222 applied either microiontophoretically or administered systemically. 3. Microiontophoretic or systemic administration of the 5-HT antagonist metergoline, which shows nanomolar affinity for the 5-HT1-binding site, also failed to attenuate the depressant responses to 5-HT. 4. Systemic administration of high doses of methysergide (30-40 mg kg-1) attenuated the depressant responses to 5-HT but did not block depressant responses to GABA or excitatory responses to glutamate. 5. The depressant effects of 5-HT were potently mimicked by the 5-HT1-like receptor agonists 5-carboxamidotryptamine and 8-OH-DPAT. 6. These results indicate that neither 5-HT2-receptors nor 5-HT3-receptors are involved in the depressant effects of 5-HT on midline brainstem neurones. The depressant effects of 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and blockade of the response to 5-HT by high doses of methysergide suggests the involvement of 5-HT1-like receptors. The lack of effect of metergoline, however, indicates that this receptor may be different from any of the 5-HT1 binding sites yet described.

Animals↗
PubMed1988

Effects of 5-hydroxytryptamine agonists and antagonists on the responses of rat spinal motoneurones to raphe obscurus stimulation.

1. The excitability of lumbar spinal motoneurones was studied in halothane-anaesthetized rats by recording with microelectrodes the amplitude of the population spike evoked antidromically by stimulation of the cut ventral roots. 2. Electrical stimulation of the nucleus raphe obscurus for 1 min at 20 Hz increased the population spike amplitude and, as shown by intracellular recording, depolarized motoneurones. This response could be mimicked by microinjection of DL-homocysteic acid into raphe obscurus but the response was not present in animals pretreated with the 5-hydroxytryptamine (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). 3. Microiontophoretically applied 5-HT had very similar effects on the extracellularly recorded population spike to those caused by stimulation of the raphe obscurus. These responses to 5-HT were larger in 5,7-DHT-pretreated animals. 4. The effects of 5-HT were potently mimicked by iontophoretically applied 5-carboxamidotryptamine but 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was without effect. 5. Antagonists were applied by microiontophoresis and also by intravenous injection. Ketanserin, the selective 5-HT2 antagonist, did not antagonize the effects of 5-HT. Neither did the 5-HT3-receptor antagonist MDL 72222 or the selective 5-HT1 binding ligand cyanopindolol. 6. The non-selective 5-HT1/5-HT2-receptor antagonist methysergide was an effective antagonist of both the effects of 5-HT and the response to raphe obscurus stimulation. Methysergide did not reduce the excitatory effects of noradrenaline. 7. It is concluded that 5-HT application and stimulation of raphe obscurus increase the excitability of motoneurones by an action on a 5-HT1-like receptor which appears to be different from the 5-HT1A-and the 5-HT1B-binding sites characterized by others.

Animals↗
PubMed1988

Type 1 fimbriate Escherichia coli stimulates a unique pattern of degranulation by human polymorphonuclear leukocytes.

Uropathogenic strains of Escherichia coli bearing mannose-sensitive (type 1) fimbriae promote a unique pattern of degranulation from human polymorphonuclear leukocytes (PMN). Significant quantities of the primary (1 degree) and tertiary (3 degree) granule markers, neutral protease-myeloperoxidase and N-acetyl-beta-D-glucosaminidase, respectively, were released by PMN in a dose- and time-dependent manner when stimulated by these defined bacterial strains. Organisms bearing mannose-resistant (P) fimbriae promoted release of only the secondary (2 degree) granule marker, vitamin B12-binding protein. When this pattern of degranulation was compared to that produced by PMN in response to a variety of soluble and particulate stimuli, only the calcium ionophore A23187 similarly triggered 1 degree and 3 degree granule marker release. All the other stimuli tested--zymosan, serum-treated and unopsonized; n-formylmethionyl-leucyl-phenylalanine; and phorbol myristate acetate--promoted release of only the 2 degree granule marker. These results demonstrate selectivity of PMN degranulation in response to a number of transmembrane signals. In addition, the capacity of E. coli to promote PMN degranulation is dependent on its phenotypic fimbrial expression, a surface characteristic which correlates significantly with its relative surface hydrophobicity as measured by binding to octyl Sepharose. Those bacteria demonstrating the greatest hydrophobicity were capable of triggering discharge of all three granule marker proteins. Thus, the mannose-sensitive fimbriae of uropathogenic E. coli may contribute significantly to their potential pathophysiologic role in renal scarring.

Cytoplasmic Granules↗
PubMed1988

The antiarrhythmic efficacy of amiodarone and desethylamiodarone, alone and in combination, in dogs with acute myocardial infarction.

Antiarrhythmic activity of amiodarone's desethyl metabolite, which accumulates during oral amiodarone therapy, has been postulated to explain the delayed onset of antiarrhythmic effects during long-term amiodarone therapy. To determine their relative antiarrhythmic efficacy, amiodarone and its desethyl metabolite, desethylamiodarone, were administered to mongrel dogs with ventricular tachycardia 24 hr after ligation of the left anterior descending coronary artery. Cumulative doses of amiodarone, desethylamiodarone, a combination of amiodarone and desethylamiodarone, or the vehicle for drug administration were given at 1 hr intervals. Both amiodarone and desethylamiodarone suppressed ventricular arrhythmias in a dose-dependent fashion. The metabolite, however, was more potent with a 50% effective concentration for suppression of premature ventricular complexes of 1.4 mg/liter compared with 4.6 mg/liter for the parent compound. Plasma and myocardial drug concentrations were similar to those measured during long-term amiodarone therapy in man, with desethylamiodarone producing greater myocardial concentrations than amiodarone for a given plasma concentration. Coadministration of the metabolite along with the parent drug resulted in suppression of arrhythmias at lower doses of amiodarone than when the latter was administered alone, and concentration-response analysis indicated an additive antiarrhythmic effect. These experiments suggest that the accumulation of desethylamiodarone that occurs with long-term oral amiodarone therapy contributes importantly to the antiarrhythmic effects of the drug, and may account for the gradual increase in antiarrhythmic action during the course of amiodarone therapy.

Amiodarone↗
PubMed1987

Improved method for the determination of the major neutral steroids and unconjugated bile acids in human faeces using capillary gas chromatography.

An improved method has been developed for the determination of the major neutral steroids (cholesterol and 5 beta-cholestan-3 beta-ol) and unconjugated bile acids (deoxycholic acid and lithocholic acid) in human faeces, using capillary gas chromatography with flame ionization detection. The freeze-dried faecal sample was subjected to a two-stage Soxhlet extraction followed by an aqueous alkali-organic solvent partition step to separate neutral steroids from bile acids. The neutral steroids were analysed as their trimethylsilyl ether derivatives on an OV-1 capillary column. The bile acids were further purified on a Sep-Pak C18 cartridge and then fractionated on a Sep-Pak SIL cartridge. Unconjugated bile acids were analysed as their methyl ester-trimethylsilyl ether derivatives also on an OV-1 capillary column. Quantitation of neutral steroids and unconjugated bile acids was achieved by reference to appropriate internal standards, added to the faecal extract immediately after the Soxhlet extraction stage. The method is being used in a study of the effect of diet on the metabolic activity of human gut flora.

Animals↗
PubMed1987

Imipramine in prepubertal major depressive disorders.

The potential effectiveness of imipramine hydrochloride (up to 5 mg/kg/d) was investigated in 53 prepubertal children suffering from major depressive disorder. Two complementary strategies were used simultaneously: a five-week, double-blind, placebo-controlled design (N = 38), and a plasma level/clinical response study (N = 30). Fifteen of the 16 children randomly assigned to active drug in the first study also participated in the second. Subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children and diagnosed according to unmodified Research Diagnostic Criteria. Response rates in the double-blind study were similar in both groups (imipramine, 56%; placebo, 68%). In the plasma level study, total maintenance plasma level (imipramine plus desipramine) was found to positively and linearly predict clinical response of the depressive syndrome (P less than .003). No evidence of a curvilinear relationship was found. Depressive hallucinations during the episode negatively predicted clinical response (P less than .05). Weight-corrected imipramine dosage did not predict either clinical response or plasma level in the individual subject. No predictors of response were found in the placebo group. These results suggest that the mean imipramine dosage was too low, and that future double-blind, placebo-controlled studies of imipramine in prepubertal major depression should include plasma level titration to above 150 ng/mL and an initial placebo washout period.

Age Factors↗
PubMed1987

An objective marker of lactate-induced panic.

There are a number of agents claimed effective in provoking panic attacks in the laboratory. For each case, however, the determination of whether an attack has occurred is largely subjective. An objective index of panic would be of great benefit in standardizing laboratory provocation studies. Using heart rate (HR) recordings during sodium lactate infusion, we developed a formula--the heart rate index (HRI)--which appears to correlate well with the subjective experience of panic. Of note is the fact that the HRI was most powerful in identifying attacks that occurred in the first 15 min of the 20-min infusions. In an accompanying study, we examined HR variability during the infusions using the successive difference mean square statistic. HR variability did not change during lactate-induced panic attacks. Therefore, tachycardia during lactate-induced panic probably does not result from decreased vagal tone to the heart.

Adult↗
PubMed1987

Urinary excretion of neutral proteinases in nephrotic rats with a glomerular disease.

A proliferative glomerulonephritis was induced in rats pre-immunized with rabbit IgG by injecting intravenously a sub-nephrotoxic dose of rabbit anti-glomerular basement membrane (GBM) IgG (A rats). Most rats (80%) developed a severe proteinuria (greater than 100 mg/24 hr) within two to five days after the injection of anti-GBM IgG. At the same time, microscopic examination of the kidneys revealed a glomerular infiltration by mononuclear phagocytes and a prominent decrease in the intensity of the colloidal iron reaction in glomeruli. A non-proliferative glomerular disease was induced in another group of rats (B rats) by intraperitoneal administration of aminonucleoside of puromycin. A marked proteinuria (greater than 100 mg/24 hr) occurred after six days in 90% of animals. Histochemical studies then revealed a decrease in staining intensity of glomeruli for polyanion. No glomerular hypercellularity was noted. In normal rats and in non-proteinuric A or B rats, the 24 hour urinary excretion of neutral proteinases ranged from 1.4 to 7.8 units (mean value +/- SEM, 4.69 +/- 0.60, N = 11), that of laminin ranged from 100 to 3,900 ng (mean value +/- SEM, 1,154 +/- 325, N = 10), and that of type IV collagen ranged from 160 to 420 ng (mean value +/- SEM, 306 +/- 26.5 ng, N = 8). In proteinuric rats from groups A (N = 11) and B (N = 9), the 24 hour urinary excretion of neutral proteinases significantly increased (mean values +/- SEM, 38.55 +/- 8.66 U for A rats and 42.17 +/- 7.92 U for B rats) and ran parallely with that of proteins, laminin and type IV collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Metabolic inactivation of vitamin D is enhanced in primary hyperparathyroidism.

1. The elimination half-time of 25-hydroxyvitamin D in plasma was estimated after intravenous injection of the radioactively labelled metabolite in seven patients with primary hyperparathyroidism before and after excision of a parathyroid adenoma. 2. The elimination half-time of 25-hydroxyvitamin D was significantly shortened in primary hyperparathyroidism and reverted towards normal after parathyroidectomy. 3. The increased metabolic clearance of 25-hydroxyvitamin D in primary hyperparathyroidism was accounted for by an increased excretion of vitamin D-derived inactivation products in the faeces. 4. Enhanced hepatic inactivation of 25-hydroxyvitamin D may be important in the development of vitamin D deficiency in primary hyperparathyroidism.

Aged↗