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Biomedical subjects

M Davies

Publications and source records attributed to M Davies.

At least 361 records · Page 20Linked to original sources
PubMed1989

Determinants of the serum concentration of 1,25-dihydroxyvitamin D in primary hyperparathyroidism.

1. The serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 44 patients with primary hyperparathyroidism. 2. In 14 patients the serum concentration of 1,25-dihydroxyvitamin D was greater than normal (142-337 pmol/l). One patient had a subnormal concentration of 1,25-dihydroxyvitamin D (36 pmol/l) but no other evidence of vitamin D deficiency. 3. The possible biological determinants of the serum concentration of 1,25-dihydroxyvitamin D were sought by multivariate analysis of relevant variables. The serum concentration of 1,25-dihydroxyvitamin D was found to be significantly and positively correlated with the serum concentrations of 25-hydroxyvitamin D (P less than 0.001) and parathyroid hormone (P less than 0.003), and with the glomerular filtration rate (P less than 0.03), and negatively correlated with the serum concentrations of calcium (P less than 0.02) and phosphate (P = 0.055) (multiple R = 0.638, P less than 0.002). 4. In primary hyperparathyroidism the major determinant of serum 1,25-dihydroxyvitamin D is the availability of precursor 25-hydroxyvitamin D. 5. The finding that serum 1,25-dihydroxyvitamin D is commonly normal in patients with primary hyperparathyroidism despite an adequate state of vitamin D nutrition, can be explained in terms of the constraining influences of hypercalcaemia and variable degrees of renal dysfunction on the biosynthesis of 1,25-dihydroxyvitamin D.

Adult↗
PubMed1989

Childhood obsessive compulsive disorder: a two-year prospective follow-up of a community sample.

A 2-year prospective follow-up of a community-based sample of adolescents previously diagnosed as having obsessive compulsive disorder (OCD) or "obsessive compulsive spectrum" disorder and a control sample was completed by clinicians experienced with OCD but blind to prior diagnosis. An initial diagnosis of OCD or "other psychiatric disorder with OC features" was most likely to predict a diagnosis of OCD at follow-up. Subclinical OCD at baseline did not strongly predict continuing psychopathology. A prior diagnosis of obsessive-compulsive personality predicted continued obsessive-compulsive symptoms but its relationship to OCD remains obscure.

Adolescent↗
PubMed1989

Attenuation of class 3 and sinus node effects of amiodarone by experimental hypothyroidism.

Amiodarone's class III effects may be due to inhibition of the cardiac effects of thyroid hormone. If so, amiodarone would not be expected to cause QT prolongation in hypothyroid subjects. The electrocardiographic (ECG) changes induced after treatment with amiodarone were compared in euthyroid and hypothyroid guinea pigs. Hypothyroidism was induced with intraperitoneal (i.p.) administration of 1 mCi I131 (eight animals). Three of these animals also received oral methimazole to block any residual thyroid hormone production. Significant increases in body weight (28 +/- 9%), RR (14 +/- 8%), QT (14 +/- 5%), and QTc (7 +/- 2%) intervals occurred after induced hypothyroidism. Pilot studies with amiodarone treatment for 4 weeks in euthyroid guinea pigs demonstrated that maximal effects on ECG intervals were achieved after 1 week of drug therapy. Therefore, both euthyroid and hypothyroid groups were treated with daily i.p. amiodarone (80 mg/kg) for 7 days. Euthyroid guinea pigs treated with amiodarone had significant increases in RR (33 +/- 10%), QT (31 +/- 15%), and corrected QT (13 +/- 11%) intervals. In contrast, when hypothyroid animals were treated with amiodarone, no statistically significant changes occurred in ECG intervals. Plasma concentrations of amiodarone did not differ between the two groups (0.7 +/- 0.6 vs. 0.7 +/- 0.4 mg/L in hypothyroid and euthyroid groups, respectively). We conclude that intact thyroid function is a prerequisite for class III and sinus node effects of amiodarone in the guinea pig. This implies that at least some of amiodarone's effects are mediated through antagonism of thyroid action.

Amiodarone↗
PubMed1989

Regulation of the gamma-aminobutyric acidA receptor by gamma-aminobutyric acid levels within the postsynaptic cell.

Synaptosomes and synaptoneurosomes were prepared from rat cerebral cortex. Comparison of the amino acid levels in the two types of organelles and of the effects of gabaculine thereon indicated that the neurosome portion of synaptoneurosomes constituted the major influencing component of the organelles. Administration to rats of inhibitors of gamma-aminobutyric acid (GABA) degradation, such as gabaculine and L-cycloserine, resulted in elevated GABA levels in synaptoneurosomes and a decrease in muscimol-stimulated Cl- up-take by the organelles. Addition of gabaculine directly to the incubation medium for the uptake assay had no effect on the Cl- transport. In contrast, administration to rats of isonicotinic acid hydrazide, an inhibitor of GABA synthesis, decreased the GABA level in synaptoneurosomes and increased the muscimol-stimulated Cl- uptake by the organelles. Although the evidence is not unequivocal, it does support the concept of GABA released from nerve endings being taken up by the postsynaptic cell, from where it exerts a regulatory influence on the functioning of the GABA receptor/ion channel complex.

Animals↗
PubMed1989

National field trial of the DSM-III-R diagnostic criteria for self-defeating personality disorder.

A national field trial of the criteria for self-defeating personality disorder was conducted in 1986. Among psychiatrists with a special interest in personality disorders there was a lack of consensus as to the need for the category in DSM-III-R. Although the diagnosis was more commonly made for female patients, the disorder was by no means rare in male patients. The diagnostic criteria for the disorder had high sensitivity and specificity. However, a series of analyses indicated that the category had limited descriptive validity and considerable overlap with borderline and dependent personality disorders.

Adult↗
PubMed1989

Growth rate in adolescents with obsessive-compulsive disorder.

In an epidemiological study of 5,596 high school students, the authors identified 20 adolescents with obsessive-compulsive disorder and compared their physical size to that of adolescents of the same sex with no obsessive-compulsive symptoms. The obsessive-compulsive boys (N = 11) were shorter and weighed less than the other boys (N = 2,479) and were shorter than a subsample of normal boys (N = 33) and boys with other psychiatric diagnoses (N = 16). Regression analysis showed a flatter growth pattern through adolescence for the obsessive-compulsive boys (although within the 95% confidence limits for the other boys), suggesting a subtle neuroendocrine dysfunction in obsessive-compulsive disorder.

Adolescent↗
PubMed1989

The way ahead: teaching with simulated patients.

This article is written to try and convince the 'sceptics' that teaching with simulated patients is the way ahead in medical education. It describes in part, the method used in the General Practice Unit at the University of Leicester and attempts to explain how it feels and what it means to be a simulated patient.

Education, Medical, Undergraduate↗
PubMed1989

Can the risk of peritonitis be predicted for new continuous ambulatory peritoneal dialysis (CAPD) patients?

Serum and overnight dialysate samples were obtained from 36 adult uraemic patients at the end of their continuous ambulatory peritoneal dialysis (CAPD) training. The samples were analysed for albumin, IgG, C3, and antistaphylococcal peptidoglycan antibody. None of the dialysate measurements correlated with the risk of peritonitis during up to one year's CAPD treatment. Nineteen of the 36 patients were retested 6 to 20 months after starting CAPD. There were significant rises in serum C3 (p less than 0.02) and albumin (p less than 0.001) and a significant fall in dialysate IgG (p less than 0.02). Eight further patients were sampled at the end of training and three weeks later. They had a significant fall in dialysate IgG (p less than 0.05). During CAPD training peritoneal permeability appears to be transiently increased. Analysis of overnight dialysate samples during training does not allow prediction of those at risk of subsequent peritonitis.

Adult↗
PubMed1989

High-dose vitamin D therapy: indications, benefits and hazards.

There are two sources of vitamin D available to man: The more important source is the cholecalciferol (vitamin D3), which is produced photochemically in the skin from the provitamin, 7-dehydrocholesterol; vitamin D ingested with food is of secondary importance, but assumes a critical role when an individual is deprived of solar exposure. Vitamin D therefore is not strictly a vitamin. A deficiency of vitamin D ultimately results in osteomalacia in adults and rickets in children, and provision of sunlight or small oral doses of the vitamin can cure this bone condition. There are, however, many less common conditions in which small doses of the vitamin are ineffective, whereas larger doses of vitamin D can achieve healing of the bone disease. These conditions are collectively called vitamin D-resistant diseases and include hypoparathyroidism, genetic and acquired hypophosphataemic osteomalacias, renal osteodystrophy, vitamin D-dependent rickets, and the osteomalacia associated with liver disease and intestinal malabsorption. Unfortunately, large doses of vitamin D continue to be prescribed for a wide variety of diseases in which there is little scientific evidence of their efficacy. The benefits and dangers of high doses of vitamin D are discussed and the problems arising from inappropriate or poorly supervised treatment with vitamin D presented. The serum concentration of the active metabolite of vitamin D, 1,25 dihydroxyvitamin D is increased in certain disease states, and the pathophysiology of some these diseases are presented. The exciting developments in tumour differentiation and the role of high doses of 1,25 dihydroxyvitamin D for the control of leukaemia and other blood and skin diseases are discussed.

Humans↗
PubMed1989

Mortality versus improvement in severe chronic asthma: physiologic and psychologic factors.

Improved outcome (1 to 10 years) of 140 asthmatic children retrospectively correlated with 8 of 49 variables in admission evaluation: (1) age of onset, (2) IgE, (3) night/early AM bronchospasm, (4) aggression, (5) severely disrupted family circumstances, (6) severe psychopathology, (7) psychotic signs, and (8) I.Q. Patients with fatal outcome (6% to 12%) deviated in the last three variables; most were 12.1 to 16.5 years, male, Black/Hispanic, aggressive, depressed and/or anxious. Clinical implications include high-risk identification on the basis of psychologic and physiologic variables, preventative measures, and consideration of residential treatment.

Adaptation, Psychological↗
PubMed1988

A sensitive chemiluminescence based immunoassay for antibody to staphylococcal peptidoglycan.

A sensitive chemiluminescence based immunoassay is described for measuring antibody to staphylococcal peptidoglycan in blood and dialysates from patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Peptidoglycan was isolated from a strain of S. epidermidis obtained from the dialysate of a CAPD patient with peritonitis and after sonication used to coat polystyrene beads. The coated beads were incubated with standard or sample and bound IgG was detected by the addition of affinity-purified goat anti-human IgG labelled with acridinium ester. After a wash stage 0.1 M nitric acid containing 0.1% hydrogen peroxide was added to the beads. Subsequently the chemiluminescence produced following the addition of 0.3 M sodium hydroxide was measured over a 2 s time interval with an automatic luminescence analyser. Using this technique the optimum dilution of serum for detecting antibodies to peptidoglycan was found to be 1/800 and for overnight effluent from CAPD patients the dilution was 1/8. Initial values of serum and dialysate antibody levels from 34 subjects are presented. This method has the advantage that it will detect concentrations of anti-peptidoglycan which are less than 1% of those in sera, the reagents remain stable for long periods and large numbers of samples can be processed on the same day.

Antibodies, Bacterial↗
PubMed1988

A new and rapid immunochemiluminometric assay for the measurement of Tamm-Horsfall glycoprotein.

Tamm-Horsfall glycoprotein was purified to apparent homogeneity from human urine by repeated precipitation with 0.58 mol/l NaCl and gel permeation chromatography under dissociating conditions on Bio-Gel A1.5M. The protein was found to consist of a single polypeptide chain of Mr 100,000 under non-reducing conditions and Mr 75,000 under reducing conditions. Antibodies to Tamm-Horsfall glycoprotein were raised in rabbits and subsequently purified by affinity chromatography using the glycoprotein linked to Sepharose 4B. The specificity of these antibodies was confirmed by Western blotting and by indirect immunofluorescence staining of human kidney tissue. The purified antibodies were labelled with 4-(2-succinimidyloxycarbonylethyl)phenyl-10-methyl-9-acridinium carboxylate fluorosulphonate, an acridinium ester, to a specific activity of 6 X 10(5) photon counts/ng of protein, and used to establish a two-site immunochemiluminometric assay for the measurement of Tamm-Horsfall glycoprotein in serum and urine. The bound and the free fractions were separated by a second antibody to Tamm-Horsfall glycoprotein linked to paramagnetic particles. The bound antibodies were quantified by chemiluminescence. The assay had a sensitivity of detection of 2 ng/ml and a working range, as determined by inter-assay precision profiles, of 30-500 ng/ml. The range in serum samples from volunteers with normal renal function (n = 92) was 74-520 ng/ml and the mean 24-h excretion rate in healthy subjects (n = 32) was 70 +/- 26 mg.

Animals↗
PubMed1988

Renal glomerular proteoglycans. An investigation of their synthesis in vivo using a technique for fixation in situ.

Newly synthesized rat glomerular [35S]proteoglycans were labelled in vivo after injecting Na2[35S]SO4 intraperitoneally. At the end of the labelling period (7 h) the kidneys were perfused in situ with 0.01% (w/v) cetylpyridinium chloride. This fixed proteoglycans in the tissue and increased their recovery 2-3-fold during subsequent isolation of glomeruli from the renal cortex. The glomeruli were fractionated by a modified osmotic lysis and detergent extraction procedure [Meezan, Brendel, Hjelle & Carlson (1978) in The Biology and Chemistry of Basement Membranes (Kefalides, N.A., ed.), Academic Press, New York; Kanwar & Farquhar (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 4493-4497] to obtain a basement membrane preparation. The proteoglycans released at each stage of the procedure were characterized using DEAE-Sephacel ion-exchange chromatography, chondroitinase ABC and HNO2 digestion and Sepharose CL-4B gel-permeation chromatography. About 85% of the [35S]proteoglycans synthesized were of the heparan sulphate variety, the remainder being chondroitin sulphate proteoglycans. Three sizes of heparan sulphate proteoglycans were identified. The largest (HS1, Kav. 0.47) accounts for 44% of the total extractable heparan sulphates. About one third of HS1 were extracted from the glomerular basement-membrane fraction with 8 M-urea and 4 M-guanidine hydrochloride but the remainder were released from the glomerulus during preparation of the fraction. The two smaller molecules (HS2, Kav. 0.56 and HS3, Kav. 0.68) accounted for 27% and 28% of the extractable heparan sulphate respectively and were not associated with the basement membrane fraction. HS1, HS2 and HS3 were also isolated from non-fixed glomeruli labelled in vivo but with much lower recovery. In glomeruli labelled in vitro, heparan sulphate accounted for only 35% of the proteoglycans, the remainder being of the chondroitin sulphate type. Proteoglycans similar to HS1, HS2 and HS3 were present in glomeruli labelled in vitro but, in addition, a large, highly charged heparan sulphate (HS1a) was extracted from the glomerular basement-membrane fraction of these glomeruli. It accounted for 6% of the total heparan sulphate.

Animals↗
PubMed1988

The purification and characterization of a glomerular-basement-membrane-degrading neutral proteinase from rat mesangial cells.

A neutral proteinase, capable of degrading gelatin, has been found in both an active and a latent form in the medium from the culture of rat mesangial cells. The latent form had an Mr of 80,000-100,000 and could be activated with either 4-aminophenylmercuric acetate or prolonged incubation at neutral pH. The active form of the enzyme was extensively purified. The estimated Mr of the purified enzyme on gel filtration was approximately 200,000, indicating that the active enzyme formed aggregates. However, analysis by SDS/polyacrylamide-gel electrophoresis under reducing conditions showed two protein bands, with Mr 68,000 and 66,000. Both proteins were found to contain proteolytic activity when run on SDS/substrate gels. The enzyme was inhibited by EDTA and 1,10-phenanthroline, but not by inhibitors for cysteine, serine or aspartic proteinases. The enzyme did not digest fibronectin, bovine serum albumin, proteoglycan or interstitial collagen. The enzyme degraded pepsin-solubilized placental type V collagen at 31 degrees C, whereas similarly solubilized type IV collagen was only degraded at higher temperatures. In addition, the neutral proteinase degraded native soluble type IV collagen. It also had activity on insoluble type IV collagen of glomerular basement membrane. The above properties suggest that the mesangial neutral proteinase belongs to the gelatinase group of metalloproteinases and that it may play a role in the normal turnover of extracellular glomerular matrix.

Animals↗
PubMed1988

Single dose versus daily intravenous aminohydroxypropylidene biphosphonate (APD) for the hypercalcaemia of malignancy.

Thirty patients with hypercalcaemia and known malignant disease were randomly allocated to receive 60 mg 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) intravenously as a single dose or as consecutive daily doses of 30 mg (two days) or 15 mg (four days). The rate of infusion was the same for each regimen (7.5 mg/hour). Calcium concentrations fell in all patients and returned to normal in all but two. Relapse of hypercalcaemia occurred after a mean of 21 days in each group. Urinary calcium excretion fell in all groups and symptoms were greatly improved. After relapse patients were retreated with APD (30 mg as a single infusion) and normocalcaemia maintained by regular infusions at two to three week intervals. APD given as a single 60 mg infusion over eight hours together with rehydration is recommended as the initial management of the hypercalcaemia of malignancy, followed by 30 mg APD roughly every two to three weeks to maintain normal or near normal serum calcium concentrations.

Calcium↗