PubMed HealthSearch

Biomedical subjects

M Walker

Publications and source records attributed to M Walker.

At least 19 recordsLinked to original sources

Pergolide can induce soluble superoxide dismutase in rat striata.

Pergolide, a dopamine receptor agonist, given daily i.p. for three weeks at 0.04 mg/kg and 0.4 mg/kg, significantly induced soluble (Cu-Zn) superoxide dismutase in the rat striatum, while having no effect on the mitochondrial (Mn) form of the enzyme. Such induction, which can also be effected by (-)-deprenyl, may help to protect against nigrostriatal degeneration.

Animals

The effect of a high carbohydrate diet on running performance during a 30-km treadmill time trial.

The purpose of the present study was to examine the influence of a high carbohydrate diet on running performances during a 30-km treadmill time trial. Eighteen runners (12 men and 6 women) took part in this study and completed a 30-km time trial on a level treadmill without modifying their food intake (trial 1). The runners were then randomly assigned to a control or a carbohydrate (CHO) group. The CHO group supplemented their normal diets with additional carbohydrate in the form of confectionery products during the 7 days before trial 2; the control group matched the increased energy intake of the CHO group by consuming additional fat and protein. The mean (SEM) carbohydrate intake of both groups was 334 (22) g before trial 1, after which the CHO group consumed 566 (29) g.day-1 for the first 3 days and 452 (26) g.day-1 for the remaining 4 days of recovery. Although there was no overall difference between the performance times for the two groups during trial 2, the CHO group ran faster during the last 5 km of trial 2 than during trial 1 [3.64 (0.24) m.s-1 vs 3.44 (0.26) m.s-1; P less than 0.05]. Furthermore, the 6 men in the CHO group ran the 30 km faster after carbohydrate loading [131.0 (5.4) min vs 127.4 (4.9) min; P less than 0.05], whereas there was no such improvement in times of the men in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Experimental evaluation of ten clinically used arterial prostheses.

The arterial grafts currently in use are classified into five basic categories; 10 different commercially available prostheses were chosen to represent these categories. The Vascutek and Bionit are made from knitted Dacron and have medium porosity, requiring preclotting by the surgeon. The DeBakey Soft Woven and Plasma TFE grafts are made from woven Dacron and have low porosity, not requiring preclotting under most circumstances. Also studied were woven and knitted grafts with leakage resistance referred to as "impervious" Dacron grafts: the Vascutek Gelseal, the Bard Albumin Coated DeBakey Vasculour II, the Microvel with Hemashield, and the albumin saturated, autoclaved DeBakey Soft Woven graft. Gore-Tex and Impra are expanded polytetrafluoroethylene grafts which do not require preclotting. For each type, five grafts 6 cm long and 8 mm in diameter were implanted in the descending thoracic aorta of healthy adult dogs for 16 weeks. The physical characteristics, biocompatibility, and healing patterns varied according to the structure and treatment of the grafts. Pretreatment with biomaterials during manufacture is quite effective in preventing transinterstices blood loss during implantation, but results in altered physical qualities, increased thrombogenicity and delayed healing in comparison to the effects of preclotting with autogenous blood at the time of implantation.

Anastomosis, Surgical

Selecting controls for schizophrenia research studies: the use of the National Adult Reading Test (NART) is a measure of premorbid ability.

The National Adult Reading Test (NART) has achieved popularity as a measure of pre-morbid intellectual ability, based on the premises that pronunciation of irregular words is unaffected in many clinical disorders and that performance is highly correlated with general intellectual ability. Recently, schizophrenia research studies have begun to appear in the literature, where the NART has been used to estimate pre-morbid ability. However, this use has preceded the basic required demonstration that, in fact, NART performance is unaffected by the schizophrenic process. In the present study, NART performance was compared across three groups; 20 acutely ill unmedicated DSM-IIIR schizophrenics, 10 other unmedicated acute psychotics, and 20 control subjects. When demographic variability between the groups was controlled for, there were no group differences in terms of NART performance. NART performance was not correlated with Brief Psychiatric Rating Scale scores, and in all three groups, no significant differences emerged when demographically predicted intelligence quotients were compared with NART estimated intelligence quotients. NART performance (predicted on the basis of demographic variables) was not significantly different from observed NART performance in any of the three experimental groups. However, within the sample with schizophrenia, NART estimated pre-morbid IQ was significantly higher than currently measured intellectual abilities. These results suggest that the National Adult Reading Test provides a reasonable estimate of pre-morbid ability in acutely ill, unmedicated schizophrenic patients.

Acute Disease

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

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

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

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

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

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

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

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