Biomedical subjects

M Davies

Publications and source records attributed to M Davies.

At least 271 records · Page 15Linked to original sources

PubMed1994

Screening for non-insulin-dependent diabetes mellitus (NIDDM): how often should it be performed?

OBJECTIVES: To examine whether a screening programme for diabetes repeated after an interval of 30 months is worthwhile both in terms of yield of new cases and continued high response rate. METHODS: Self testing for postprandial glycosuria was used as it has been shown to have a good response rate, a good yield of cases of diabetes, and a sensitivity and specificity which compares favourably with more expensive and invasive screening methods. A total of 3231 subjects aged 45-70 years in one practice were screened on two occasions 30 months apart. Eighty seven subjects known to have diabetes were excluded. This number included five new patients who had presented since the initial screen; two of whom had moved into the practice, one who screened positive at the initial screen but failed to attend for the oral glucose tolerance test (OGTT), and two subjects who had screened negative, the first presenting 24 months after screening. RESULTS: At repeat screening the return rate was lower than at the first screening (72.5% v 79.2%, P < 0.0001). Glycosuria was detected in 52 subjects (2.3%), at the repeat screening, similar to that at the initial screen. Attendance for the OGTT after a positive screening test was 93.2%. Only six subjects of the 24 with glycosuria but normal glucose tolerance at initial screen were found to have glycosuria again; repeat OGTTs were all normal. Of the remaining 46 subjects, 10 had non-insulin-dependent diabetes mellitus (NIDDM) and five impaired glucose tolerance (IGT). The number of subjects with diabetes was not significantly different from that at the initial screening (0.44% v 0.72%, P = 0.2). CONCLUSIONS: Repeat screening after 30 months has a high response rate, similar rate of detection of glycosuria, and a further yield of 0.44% of newly diagnosed cases of diabetes. A screening programme detecting postprandial glycosuria identifies additional diabetic subjects 30 months after a previous screening programme.

Age Factors↗

PubMed1994

Abnormal synthesis of 1,25-dihydroxyvitamin D in patients with malignant lymphoma.

High serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D] can occur with hypercalcemia in malignant lymphoma. We have investigated the potential for abnormal vitamin D metabolism by giving a single oral dose of 25-hydroxyvitamin D (25OHD) in 10 lymphoma patients (8 Hodgkin's and 2 T-cell) and 7 controls. Serum 25OHD increased similarly in both groups (peak concentrations, 114.1 +/- 9.5 vs. 123.9 +/- 9.6 nmol/L). In controls, serum calcium and PTH did not change after treatment [calcium, 2.31 +/- 0.02 and 2.33 +/- 0.02 mmol/L (mean +/- SEM); PTH, 21.6 +/- 4.0 and 25.4 +/- 4.3 ng/L] 1,25-(OH)2D increased within the normal range from [median (range)] 81 (48-125) to 117 (91-156) pmol/L. In lymphoma patients, serum calcium increased from 2.29 +/- 0.04 to 2.40 +/- 0.06 mmol/L (P = 0.03), PTH decreased from 12.9 +/- 2.6 to 8.0 +/- 1.9 ng/L (P = 0.06), and one patient became hypercalcemic (2.92 mmol/L). Serum 1,25-(OH)2D became supranormal in 6 lymphoma patients; the group median rose from 74.5 (46-180) to 151 (120-487) pmol/L; this peak response differed from that in the controls (P = 0.019). Lymph node and spleen cells from a patient with T-cell lymphoma synthesized [3H]1,25-(OH)2D3 from [3H] 25OHD3 in vitro. The data suggest that abnormal production of 1,25-(OH)2D in lymphoma may be more common than previously recognized given an adequate supply of precursor 25OHD and provide further evidence for the extrarenal synthesis of 1,25-(OH)2D in this condition.

Calcifediol↗

PubMed1994

Constitutive synthesis of 1,25-dihydroxyvitamin D3 by a human small cell lung cancer cell line.

One of 16 human small cell lung cancer cell lines examined was shown to synthesize a metabolite resembling 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. The NCI H82 line converted 25-hydroxyvitamin D3 (25OHD3) into a compound indistinguishable from 1,25-(OH)2D3 in 3 different high performance liquid chromatography systems. Electron impact mass spectra for the trimethylsilylethers of the metabolite and authentic 1,25-(OH)2D3 were indistinguishable. Binding to an anti-1,25-(OH)2D3 antibody was identical for the metabolite and authentic 1,25-(OH)2D3, whereas administration to rats in vivo caused equivalent stimulation of calcium transport measured in vitro in duodenal sacs. Activity of the H82 1 alpha-hydroxylase appears to be substrate dependent and is not stimulated by PTH, suggesting that it is similar to the enzyme expressed by activated macrophages and other cell types at extrarenal sites. Inhibition by ketoconazole indicates that, like the renal and extrarenal enzymes, the H82 enzyme is cytochrome P450 dependent. These data indicate that the H82 small cell lung cancer cell line constitutively expresses 25-hydroxyvitamin D3-1 alpha-hydroxylase and can synthesize 1,25-(OH)2D3.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMed1994

A mathematical model of intraluminal and intracavitary brachytherapy.

The adaptation of the linear-quadratic model to allow for the effect of tumour regression and clonogen repopulation between initial teletherapy and subsequent brachytherapy has been extended to include the geometrical conditions encountered in intraluminal and intracavitary brachytherapy. For a radiation line source placed at the centre of a lumen or cavity, regression of any endoluminal tumour towards its mural origin will not result in any change in the minimum brachytherapy-tumour dose with time. In contrast, regression of transmural tumour will cause a potentially advantageous increase in the minimum brachytherapy-tumour dose with time. The latter effect will be opposed by tumour clonogen repopulation. The log(e) cell kill due to brachytherapy has been calculated for tumours of diameters 2, 4 and 6 cm at completion of teletherapy. The centres of the tumours were assumed to be at distances of 0, 1 and 2 cm from the radiation source. Tumour linear regression rates (lambda) ranging from 0.025 to 0.25 per week and tumour clonogen doubling times (Tp) of 2.5, 5 and 15 days were used in the calculations. The results demonstrate the critical importance of the distance of the tumour centre from the line source as well as the influence of tumour diameter, lambda and Tp. In some instances, both maximum and minimum values of log(e) cell kill occur. Calculations of tumour cure probabilities reveal that these variations in log(e) cell kill predicted by the model can produce highly significant differences in tumour control rates. Where the relevant parameters can be assessed directly or estimated from previous experience, the model provides a basis for the design of future intraluminal or intracavitary brachytherapy protocols.

Brachytherapy↗

PubMed1994

Maternal smoking during pregnancy and smoking by adolescent daughters.

OBJECTIVES: Since cigarette smoking in adolescence represents a crucial entry point in the progression to illicit drugs, risk factors for adolescent smoking have public health implications. The influence of mothers on children's smoking appears to be greater than that of fathers. To explain the selective influence of mothers, we examined the consequences of maternal smoking during pregnancy in two longitudinal samples. METHODS: Analyses were conducted on follow-up interview data from two dyadic samples of mothers and firstborn adolescents for whom data on maternal smoking during and after pregnancy were available (192 mother-child pairs originating from New York State and 797 dyads from a national sample). RESULTS: In both samples, maternal smoking during pregnancy, when postnatal smoking was controlled, selectively increased the probability that female children would smoke and would persist in smoking (adjusted odds ratios of about 4). CONCLUSIONS: The findings suggest that nicotine or other substances released by maternal smoking can affect the fetus, perhaps through the nicotinic input to the dopaminergic motivational system, so as to predispose the brain in a critical period of its development to the subsequent addictive influence of nicotine consumed more than a decade later in life.

Adolescent↗

PubMed1994

Operating from a distance--new directions in perioperative nursing education.

Australia is home to only 17 million people, most of whom live in the coastal areas around the State capital cities. But there are numerous smaller cities, towns and communities scattered in the inland rural areas. Communicating between these centres has proved to be quite a challenge since early settlers arrived and remains so today. Providing education to the population who live away from the capital cities and university centres continues to be a challenge. Many universities, in an attempt to overcome the distance factor, offer external studies courses--the old correspondence courses. Providing a specialty nursing course via external studies had never been attempted in Australia until the NSW College of Nursing took the plunge in 1990 and pioneered a certificate course in perioperative nursing. We were encouraged by the success of a similar venture in Canada some years before.

Certification↗

PubMed1994

Interrelationship between serum concentrations of 1,25-dihydroxyvitamin D, parathyroid hormone and renal haemodynamics after low dose cyclosporin.

It is unclear whether cyclosporin A (CsA) alters the synthesis of 1,25-dihydroxyvitamin D3 [1,25(OH)2D] by the normal human kidney. Serial changes in 1,25(OH)2D, parathyroid hormone (PTH), GFR and renal blood flow were compared in 14 patients with psoriasis who were being treated with less than 5 mg/kg/day of cyclosporin for 3 months. GFR fell significantly although there were no significant changes in serum 1,25(OH)2D, 25-hydroxyvitamin D or PTH. Absolute values for GFR and PTH were negatively correlated (rP = -0.54; p < 0.001) as were the changes in GFR and PTH observed during CsA therapy (rP = -0.73; p < 0.05). The significant fall in serum magnesium was not significantly correlated with changes in PTH. The close relationship between changes in GFR and PTH suggests that a reduction of GFR within the normal range is enough to stimulate production of PTH. CsA does not appear to stimulate the synthesis of 1,25(OH)2D3 in man.

Adolescent↗

PubMed1994

Caries prevalence in Australasia.

The prevalence of caries in Australian children has decreased markedly since its peak in the 1950s. More than half the child population has no experience of caries. However, a small minority, approximately one in sixteen, may be considered still at high risk with an unacceptably large number of teeth with caries experience. This is leading to the addition of high risk strategies to programmes for caries prevention and management. While the prevalence of caries in children has decreased, caries experience in adults has remained widespread and extensive. The majority of teeth in dentate adults have experienced caries. Comparisons over time indicate little change in caries experience in middle-aged adults, but an increase in filled teeth and decrease in missing teeth. The prevalence of caries has not changed substantially, but the management of the disease has moved towards maintenance and repair of teeth. Tooth retention has increased over recent decades. Edentulism has decreased markedly and dentate adults are retaining more teeth. Sizeable increases in the pool of teeth at risk of caries give emphasis to the continued need for preventive measures to reduce caries activity in adults.

Adolescent↗

PubMed1994

Anabolic steroid use by amateur athletes: effects upon psychological mood states.

Twenty-one male amateur athletes attending a Welsh needle-exchange clinic, were asked to complete the Buss-Durke Inventory on feelings of hostility/aggression, and a feeling state questionnaire. All were weight training in local gyms in order to increase their body mass. They were also using high doses of anabolic steroids during 6-14 week cycles, while between these cycles they were steroid free. Subjects reported significantly higher feelings of aggression, aggression towards objects, verbal aggression, and aggression during training (but not physical aggression towards people), during the on-steroid periods. Other changes on-drug, included significantly higher feelings of alertness, irritability, anxiety, suspiciousness, and negativism. While increased aggressiveness has been noted in many previous studies, the present findings demonstrate that anabolic steroids can affect a wide range of psychological mood states.

Adult↗

PubMed1993

Internodal potassium currents can generate ectopic impulses in mammalian myelinated axons.

Positive clinical symptoms can arise from ectopic action potentials in several disorders of myelinated axons. Here we report that an elevated K+ concentration in the periaxonal, internodal space can cause internodal K+ currents to become excitatory, resulting in slow potential oscillations and associated bursts of ectopic spikes. Ectopic firing may therefore be favoured by conditions in which periaxonal K+ buffering is compromised.

Action Potentials↗

PubMed1993

Homology cloning of rat 72 kDa type IV collagenase: cytokine and second-messenger inducibility in glomerular mesangial cells.

Glomerular mesangial cells (MC) play a central role in the synthesis and turnover of the glomerular extracellular matrix. Prior studies [Davies, Thomas, Martin and Lovett (1988) Biochem. J. 251, 419-425; Martin, Davies, Thomas and Lovett (1989) Kidney Int. 36, 790-801] have characterized at the protein level a 72 kDa type IV collagenase that is secreted by cultured human and rat MC. While exposure of most cell types to interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) or phorbol ester has little or even an inhibitory effect on 72 kDa type IV collagenase secretion, these factors significantly increased the synthesis of this enzyme by rat MC. Given this divergent pattern of expression, a homology-based PCR cloning strategy using rat MC cDNA templates was employed to define at the molecular level the structure of the mesangial 72 kDa type IV collagenase. The nucleotide sequence within the open reading frame of the rat mesangial 72 kDa type IV collagenase cDNA diverges from the sequence of the human homologue by approx. 9%. The divergence in the 3' untranslated region was much more extensive. Steady-state levels of the 3.1 kb transcript of the 72 kDa type IV collagenase were low or undetectable in resting MC, but were greatly stimulated following incubation with IL-beta, TNF-alpha or phorbol ester. None of these factors induced synthesis by MC of the closely related 92 kDa type IV collagenase. Synthesis by MC of the 72 kDa type IV collagenase was also induced by second-messenger analogues, including 8-bromo-cyclic AMP and forskolin. It is concluded that MC regulate the expression of this enzyme in an unusual, tissue-specific fashion. Cytokine and second-messenger inducibility may contribute to the enhanced expression of the enzyme during glomerular inflammatory disorders.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1993

Comorbidity of DSM-III-R eating disorders and personality disorders.

The purpose of this study was to assess the relationship of eating disorders to personality disorders. Two hundred subjects were independently administered the Structured Clinical Interview for DSM-III-R (SCID) and the Personality Disorder Examination (PDE) face-to-face by two experienced clinicians. One hundred forty-six also completed the Personality Diagnostic Questionnaire-Revised (PDQ-R). Rates of personality disorder among patients with and without eating disorders were determined by each of the three instruments. Comorbidity between bulimia nervosa and anorexia nervosa and a conservative estimate of individual Axis II disorders was examined. Eating disorders with and without personality disorders were compared on age at onset and two measures of illness severity. Results indicate that the association, in general, between personality disorders and eating disorders varies by diagnostic method. Bulimia nervosa, however, is associated with borderline personality disorder and anorexia nervosa with avoidant personality disorder. Eating disorders with personality disorders are characterized by chronicity and low levels of functioning compared with eating disorders without personality disorders.

Adolescent↗

PubMed1993

Relationships between change in aerobic fitness and changes in blood pressure and plasma lipids in men and women: the "Adelaide 1000" 4-year follow up.

The aim was to assess relationships between increased aerobic fitness sustained over 4 years, and changes in blood pressure (SBP and DBP) and lipids. Measurements were made of BP, lipids, weight, and fitness in 1000 middle-aged men and women entering a fitness programme, and were repeated 2 and 4 years later. The 342 men and women selected for this 4-year follow-up were either consistent fitness "gainers" (improved by > 5%) or "non-gainers" (improved by < or = 5%) at 2 and 4 year stages. For men, comparisons of these groups and multiple regression analyses failed to show significant relationships between changes in fitness and risk factors over the 4 year period. For women, "gainers" improved more than "non-gainers" in SBP (by 4 mmHg, p < 0.03), HDL/cholesterol ratio (by 0.01 mmol l-1, p < 0.0001), and triglycerides (by 0.02 mmol l-1, p < 0.05); regression analyses resulted in a significant relationship between changes in fitness and SBP (B = 0.012, p < 0.05). The study gave weak support to the existence of causal relationships between aerobic fitness and CHD risk factors for women, and no support for men.

Adult↗

PubMed1993

Effects of cholinergic agonists on diacylglycerol and intracellular calcium levels in pancreatic beta-cells.

We have studied the effects of cholinergic agonists on the rates of insulin release and the concentrations of diacylglycerol (DAG) and intracellular free Ca2+ ([Ca2+]i) in the beta-cell line MIN6. Insulin secretion was stimulated by glucose, by glibenclamide and by bombesin. In the presence of glucose, both acetylcholine (ACh) and carbachol (CCh) produced a sustained increase in the rate of insulin release which was blocked by EGTA or verapamil. The DAG content of MIN6 beta-cells was not affected by glucose. Both CCh and ACh evoked an increase in DAG which was maximal after 5 min and returned to basal after 30 min; EGTA abolished the cholinergic-induced increase in DAG. ACh caused a transient rise in [Ca2+]i which was abolished by omission of Ca2+ or by addition of devapamil. Thus, cholinergic stimulation of beta-cell insulin release is associated with changes in both [Ca2+]i and DAG. The latter change persists longer than the former and activation of protein kinase C and sensitization of the secretory process to Ca2+ may underlie the prolonged effects of cholinergic agonists on insulin release. However, a secretory response to CCh was still evident after both [Ca2+]i and DAG had returned to control values suggesting that additional mechanisms may be involved.

Acetylcholine↗

PubMed1993

Tamm Horsfall protein binds to a single class of carbohydrate specific receptors on human neutrophils.

Several studies have implicated urinary Tamm Horsfall protein (THP) in the aetiology of tubulointerstitial inflammation. Previous research has demonstrated that particulate THP will initiate inflammatory activation of human polymorphonuclear leukocytes (PMN) through a trypsin sensitive mechanism. The present study describes the binding of 125I-monomeric THP to human PMN at 4 degrees C and demonstrates that radiolabeled THP binds to PMN in a saturable, reversible and time dependent manner. The addition of 400 to 600 ng 125I-THP/2 x 10(6) PMN was sufficient to achieve saturable binding. Scatchard analysis of binding data yielded linear plots suggesting a single class of receptors with a mean density of 26218/cell and a dissociation constant (KD) of 4.2 x 10(-9) M. Binding reached steady state by 15 minutes and could be rapidly displaced by the addition of an excess of unlabeled THP. The KD calculated from experimentally derived kinetic rate constants (k1 and k2) was of a similar order of magnitude (0.9 x 10(-9) M) to that generated from Scatchard plots. In addition 125I-THP bound specifically to PMN plasma membrane immobilized on nitrocellulose filters, a process which could be inhibited by unlabeled monomeric THP. Chemical modification of unlabeled THP abolished its capacity to inhibit binding. Specific inhibition studies showed that N-acetylneuraminic (sialic) acid dose dependently displaced the binding of 125I-THP to immobilized PMN membranes at concentrations up to 100 mM. These results indicate that the reported activation of human PMN by THP is mediated through a single class of sialic acid-specific cell surface receptors.

Carbohydrate Metabolism↗

PubMed1993

Human peritoneal mesothelial cells synthesize interleukin-6: induction by IL-1 beta and TNF alpha.

Recent studies have demonstrated increased levels of IL-6 in the peritoneal cavity during CAPD peritonitis. The current investigation was initiated (i) to examine the human peritoneal mesothelial cell (HPMC) as a possible source of this secreted IL-6 and (ii) to characterize the released product and examine its regulation by other cytokines. Unstimulated HPMC under growth arrested conditions released IL-6 in a time dependent manner. After 24-hour HPMC IL-6 release (mean +/- SEM, N = 13) (expressed as pg/micrograms cell protein) was 1.67 +/- 0.33. Stimulation of HPMC with IL-1 beta or TNF alpha resulted in a time (increasing up to 48 hr) and dose dependent IL-6 generation. After 24 hours the levels induced by IL-1 beta and TNF alpha (both at 1000 pg/ml) were (mean +/- SEM, N = 13) 19.08 +/- 2.98 and 6.62 +/- 1.72, respectively. Stimulation with combinations of IL-1 beta and TNF alpha resulted in additive increases in IL-6 release. This release could be inhibited by co-incubation with anti-IL-1 beta and/or anti-TNF alpha antibodies. The level of released HPMC IL-6 measured by immunometric assay (ELISA) correlated directly with that detected in the 7TD1 IL-6 bioassay (r = 0.63; P < 0.001). Western blot analysis of concentrated HPMC supernatants using specific anti-IL-6 antibody demonstrated immunoreactive bands at 23 and 28 Kd following IL-1 beta or TNF alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1993

Left ventricular hypertrophy and myocardial ischaemia in hypertension: the THAMES Study.

A multicentre epidemiological study to detect the prevalence of myocardial ischaemia in hypertensive left ventricular hypertrophy (LVH) was performed in 188 asymptomatic male hypertensives (131 treated). The mean age was 55 (range 40-82) years with blood pressure (BP) > or = 160/100 mmHg or a systolic BP > or = 180 mmHg. The participants were screened with echocardiography, and left ventricular hypertrophy (LVH), defined as LV mass index (LVMI) > or = 130 g.m-2, was found in 127 (68%), of whom 95 were on antihypertensive treatment. Patients with LVH underwent a maximal bicycle ergometer exercise test and significant ST depression, indicating possible stress-induced ischaemia, was found in 29 men (23%). These subjects were subjected to exercise thallium-201 scintigraphy, which was normal in 14 but showed reversible perfusion defects in 15. Thus, a high prevalence of LVH (70%) was detected in male hypertensives selected only on age and BP. In addition, although chest pain on exertion excluded patients from entry, a substantial portion had signs of ischaemia (23% on exercise ECG alone, and in 52% confirmed by thallium scan). The prevalence of these risk factors should be considered when evaluating hypertensive patients.

Adult↗

PubMed1993

The Diagnostic Interview Schedule for Children-Revised Version (DISC-R): I. Preparation, field testing, interrater reliability, and acceptability.

OBJECTIVE: To describe the history and assessment strategies used to investigate and revise the Diagnostic Interview Schedule for Children (DISC), a highly structured interview form used by lay interviewers to elicit diagnostic criteria for the common psychiatric disorders of childhood and adolescence. METHOD: Revision was based on clinical and community data that identified unreliable and undiscriminating items in an earlier version of the instrument (DISC-1). A field study was carried out with 74 parent-child pairs. Interrater reliability and acceptability to patients was high. Accompanying papers describe the test-retest and construct validity of the instrument. CONCLUSIONS: Taken together, the findings suggest that the DISC is an acceptable, brief, inexpensive, and convenient instrument for ascertaining a comprehensive range of child and adolescent diagnoses whose methodological properties are comparable with other child diagnostic instruments.

Adolescent↗