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Biomedical subjects

M Walker

Publications and source records attributed to M Walker.

At least 379 records · Page 21Linked to original sources
PubMed1992

Acute metabolic and hormonal responses to the inhibition of lipolysis in non-obese patients with non-insulin-dependent (type 2) diabetes mellitus: effects of acipimox.

1. Increased rates of fatty acid oxidation are frequently observed in patients with non-insulin-dependent diabetes mellitus and may contribute to hyperglycaemia by both decreasing peripheral glucose disposal and, more importantly, by increasing the rate of gluconeogenesis and therefore hepatic glucose output. Despite this relationship between lipid and carbohydrate metabolism, fasting glucose concentrations do not fall acutely in patients with non-insulin-dependent diabetes mellitus when plasma non-esterified fatty acid concentrations and lipid oxidation rates are decreased, questioning the importance of this interaction to glycaemic control. We have therefore measured the acute changes that occur 120-150 min after administration of 500 mg of the antilipolytic agent acipimox in eight non-obese male patients with non-insulin-dependent diabetes mellitus. 2. After administration of acipimox, lipolysis was inhibited as reflected by lower plasma non-esterified fatty acid (0.05 +/- 0.02 versus 0.55 +/- 0.05 mmol/l, P less than 0.001) and blood glycerol (8 +/- 1 versus 56 +/- 8 mumol/l, P less than 0.001) concentrations. The lipid oxidation rate was decreased (0.63 +/- 0.05 versus 1.02 +/- 0.08 mg min-1 kg-1, P less than 0.001), whereas there was a significant increase in the carbohydrate oxidation rate (1.93 +/- 0.17 versus 1.22 +/- 0.18 mg min-1 kg-1, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1992

The replicative restriction of lymphocytotropic isolates of HIV-1 in macrophages is overcome by TGF-beta.

In vitro exposure of human blood monocyte-derived macrophages to T-cell tropic human immunodeficiency virus (HIV) isolates fails to establish a productive viral infection. Several studies have shown that such preferential HIV-1 replication in T cells or in mononuclear phagocytes (HIV tropism) may be determined by distinct viral characteristics. In the present study it was demonstrated that transforming growth factor-beta (TGF-beta), a factor known to be produced by platelets, macrophages, and other cells present at a wound site, can act as a mediator in overcoming the lymphocytotropic restriction of several well-characterized viral isolates of HIV-1 (i.e., LAV, Z84, pLAI, NY5). Macrophages infected with these isolates show cytopathic changes comparable to those seen upon infection with the monocytotropic isolate ADA. To achieve this effect with TGF-beta, the factor must be present after the infection period. The emerging virus retains its original cellular tropism. Based on these observations the authors propose a role for TGF-beta in the establishment and progression of HIV infection and disease.

Cells, Cultured↗
PubMed1992

Is epidermal cell proliferation in psoriatic skin grafts on nude mice driven by T-cell derived cytokines?

Plasminogen activity and DNA synthesis by epidermal cells have been reported to be doubled in psoriatic skin grafts compared with grafts of normal skin 6 weeks after transplantation to nude mice. In our study human lymphocytes disappeared from such grafts within 48 h whilst some DR-positive human dendritic cells were retained in the grafts for up to 4 weeks. However, the grafts were infiltrated by Thy 1.2+ mouse lymphocytes within 6 days and this infiltration persisted at a moderate level throughout the observation period. It consisted of perivascular aggregates, scattered dermal and papillary T cells, and some mouse T cells were also found in the epidermal compartment. Grafts of psoriatic and non-psoriatic control skin were infiltrated to a similar extent, suggesting a low-grade rejection response against the human xenografts. These findings raise the possibility that psoriatic keratinocytes are responding abnormally to inflammatory cytokines released by mouse lymphocytes reacting against the skin grafts.

Animals↗
PubMed1992

The effects of the specific serotonin antagonist ICI 169,369 on the pituitary hormone response to insulin-induced hypoglycaemia in humans.

OBJECTIVE: To examine the role of serotonin in pituitary hormone release by studying the effect of a specific 5HT2 receptor antagonist, ICI 169,369, on the ACTH, prolactin, growth hormone and AVP response to insulin-induced hypoglycaemia in healthy humans. DESIGN: A double-blind, within-subject trial using a crossover design to compare the effect of placebo with two doses of ICI 169,369 on pituitary hormone responses to insulin-induced hypoglycaemia. PATIENTS: Ten healthy subjects were studied in the low-dose (30 mg x 2) limb and 11 healthy volunteers in the high-dose (80 mg x 2) limb. MEASUREMENTS: Plasma concentrations of prolactin, growth hormone, ACTH, cortisol and AVP, and blood glucose. RESULTS: In the low-dose study, pretreatment with 30 mg ICI 169,369, 10 and 2 hours before the study, had no effect on the fall in blood glucose or the rise in plasma ACTH, prolactin, growth hormone, AVP or plasma cortisol following insulin injection, when compared with placebo. In the high-dose study the effect of a higher dose (80 mg) of ICI 169,369 on the pituitary hormone response to hypoglycaemia was compared with that of placebo. Although the fall in blood glucose was similar following drug (4.3 +/- 0.1 to 1.5 +/- 0.5 mmol/l, mean +/- SEM, P less than 0.001) and placebo (4.3 +/- 0.1 to 1.4 +/- 0.4 mmol/l, P less than 0.001), the rise in plasma AVP was lower (P less than 0.05) following pretreatment with drug (0.5 +/- 0.2 to 2.1 +/- 0.6 pmol/l, P less than 0.05) than with placebo (0.7 +/- 0.2 to 3.4 +/- 0.9 pmol/l, P less than 0.01). CONCLUSIONS: The ACTH, prolactin, growth hormone and cortisol responses were unaffected by ICI 169,369. The data are compatible with an inhibitory effect of the serotonin antagonist ICI 169,369 on the AVP, but not the ACTH, prolactin or growth hormone response to insulin-induced hypoglycaemia in humans.

Adrenocorticotropic Hormone↗
PubMed1992

A double blind study of the effect of acipimox on serum lipids, blood glucose control and insulin action in non-obese patients with type 2 diabetes mellitus.

Hyperlipidaemia, in particular raised concentrations of serum triglycerides, together with raised plasma non-esterified fatty acid concentrations, is common in patients with Type 2 (non-insulin-dependent) diabetes mellitus and may be associated with insulin insensitivity. Thirty non-obese Type 2 diabetic patients (15 controlled with diet alone and 15 with diet plus oral sulphonylurea therapy) were therefore recruited to take part in a double-blind, randomized, crossover comparison of acipimox (250 mg three times daily for 3 months) and placebo. Serum lipids, blood glucose control, insulin sensitivity, and glucose tolerance were measured before and after each treatment period. There was a significant decrease in serum triglycerides (2.05 +/- 1.08 vs 2.91 +/- 1.75: p < 0.005), cholesterol (5.66 +/- 1.02 vs 6.26 +/- 1.17: p = 0.0005), and apoprotein B (1.32 +/- 0.23 vs 1.44 +/- 0.25: p < 0.05) while HDL cholesterol and apoprotein A-1 concentrations were unchanged. There was no change in blood glucose control measured by fasting glucose, insulin, and HBA, concentrations, but there was a significant improvement in insulin action assessed by glucose-insulin infusion. Although plasma non-esterified fatty acid concentrations were lower during the oral glucose tolerance test after acipimox, there was no difference in either the peak or 2-h plasma glucose concentrations and the total area under the glucose curve did not change. Acipimox was well tolerated and no patients withdrew from the study for drug-related symptoms. Thus, acipimox effectively lowers serum cholesterol and triglycerides in patients with Type 2 diabetes without adversely altering blood glucose control, and appears to improve insulin sensitivity.

Analysis of Variance↗
PubMed1992

Childhood blood pressure, body build, and birthweight: geographical associations with cardiovascular mortality.

STUDY OBJECTIVE: The aim was to examine whether blood pressure, body build, and birthweight differ between areas of England and Wales with widely differing adult cardiovascular mortality rates. DESIGN: This was a cross sectional survey of children in five towns with exceptionally high and five towns with exceptionally low current adult cardiovascular mortality. SETTING: The study was a school based survey. SUBJECTS: 3842 children aged 5.0-7.5 years were selected by stratified random sampling of primary schools (response rate 76%). MEASUREMENTS AND MAIN RESULTS: Blood pressure, pulse rate, height, and weight were measured and birthweight was assessed by maternal recall. Children in towns with high cardiovascular mortality rates were significantly shorter than those in towns with low cardiovascular mortality rates (mean difference 0.9 cm, 95% confidence interval 0.4 to 1.4 cm) and had slightly higher body mass indices (mean difference 0.12 kg/m2, 95% CI -0.03 to 0.27 kg/m2). Mean birthweights were slightly lower in high mortality towns (mean difference 34 g, 95% CI -10 to 78 g), while the proportion of children with low birthweight (< 2500 g) (8.1%) was significantly higher than that in low mortality towns (5.5%) (p = 0.005). Mean differences in blood pressure between high and low mortality towns were small and non-significant, even after adjustment for height. The differences in height between high and low mortality towns were largely independent of social class. However, differences in mean birthweight were markedly reduced once social class was taken into account. CONCLUSIONS: No geographical relationship between childhood blood pressure and adult cardiovascular mortality was detected. Although it is possible that the differences in mean height and body mass index between towns with differing adult cardiovascular mortality may have implications for future patterns of health in these towns, the absence of marked differences in birthweight and blood pressure suggests that hypotheses proposing a direct relationship between intrauterine experience and adult cardiovascular mortality will have limited relevance to geographical variation in cardiovascular disease in this generation.

Adult↗
PubMed1992

Metabolic effects of suppression of nonesterified fatty acid levels with acipimox in obese NIDDM subjects.

NEFAs characteristically are elevated in obese NIDDM patients in both the basal state and after insulin. This elevation might aggravate glycemic control both by decreasing peripheral glucose disposal (glucose-fatty acid cycle), and by increasing HGO. Thus, lowering plasma NEFA levels might improve carbohydrate metabolism. We therefore measured HGO and fuel use (by indirect calorimetry) both in the basal state and during the last 30 min of a hyperinsulinemic clamp (0.025U.kg-1.h-1) in 8 obese NIDDM patients (BMI 34.8 +/- 1.0 kg/m2) after complete overnight suppression of plasma NEFA levels with acipimox, a new nicotinic acid analogue. After acipimox, mean basal plasma NEFA and glycerol levels were lower than control values (0.11 +/- 0.02 vs. 0.65 +/- 0.04 mM, P < 0.001; and 16 +/- 3 vs. 68 +/- 7 microM, P = 0.004, respectively) and were accompanied by a fall in lipid oxidation (acipimox vs. placebo: 16.1 +/- 1.2 vs. 38.8 +/- 2.4 mg.m-2 x min-1; P < 0.001) and a rise in glucose oxidation (91.1 +/- 6.2 vs. 54.1 +/- 9.0 mg.m-2 x min-1; P = 0.002). Basal HGO and fasting plasma glucose levels were lower (94.1 +/- 9.2 vs. 118.5 +/- 9.5 mg.m-2 x min-1, P = 0.01; and 8.3 +/- 1.2 vs. 9.8 +/- 1.2 mM; P < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1992

Breastfeeding the premature infant.

Breastfeeding the premature infant is both possible and desirable. Premature infants derive benefits from breast milk that they can not receive from formula. Nutritional issues look at the components of breast milk as they relate to brain growth and development and disease protection in the acute setting and later in childhood. Recommendations for clinical practice are provided, as are information on expressing and collecting milk, breastfeeding readiness, putting the infant to breast, and discharge planning.

Adult↗
PubMed1992

Non-consulters and high consulters in general practice: cardio-respiratory health and risk factors.

The 1990 General Practitioner contract requires that health promotion and illness prevention services should be provided to all patients aged 16-74 years. Consultation rates over a period of three years were examined in 7010 middle-aged men in Great Britain to compare the cardio-respiratory health and risk factor status of non-consulters (men who did not consult in three years) with those of average consulters (men who consulted 3-5 times in three years) and high consulters (men who consulted 24 or more times in three years) to assess their relative need for health promotion and illness prevention services. The non-consulters (n = 1025) were remarkably similar to the average consulters (n = 1585) in health and lifestyle characteristics. The high consulters (n = 306) had a greater burden of ill-health and a less healthy lifestyle. Chest pain on exertion, chronic bronchitis, breathlessness or wheeze were present in 23 per cent of non-consulters, 27 per cent of average consulters and over 50 per cent of high consulters. Similarly, 48 per cent of the non-consulters smoked, drank heavily or were obese compared with 47 per cent of the average consulters and 61 per cent of the high consulters. The prevalence of recall of high blood pressure which had been diagnosed by a doctor rose from 6 per cent in non-consulters and 10 per cent in average consulters to 29 per cent in high consulters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗