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Biomedical subjects

P Collins

Publications and source records attributed to P Collins.

At least 19 recordsLinked to original sources
PubMed2002

Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor.

The abnormalities of lipid metabolism observed in cancer cachexia may be induced by a lipid-mobilizing factor produced by adenocarcinomas. The specific molecules and metabolic pathways that mediate the actions of lipid-mobilizing factor are not known. The mitochondrial uncoupling proteins-1, -2 and -3 are suggested to play essential roles in energy dissipation and disposal of excess lipid. Here, we studied the effects of lipid-mobilizing factor on the expression of uncoupling proteins-1, -2 and -3 in normal mice. Lipid-mobilizing factor isolated from the urine of cancer patients was injected intravenously into mice over a 52-h period, while vehicle was similarly given to controls. Lipid-mobilizing factor caused significant reductions in body weight (-10%, P=0.03) and fat mass (-20%, P<0.01) accompanied by a marked decrease in plasma leptin (-59%, P<0.01) and heavy lipid deposition in the liver. In brown adipose tissue, uncoupling protein-1 mRNA levels were elevated in lipid-mobilizing factor-treated mice (+96%, P<0.01), as were uncoupling proteins-2 and -3 (+57% and +37%, both P<0.05). Lipid-mobilizing factor increased uncoupling protein-2 mRNA in both skeletal muscle (+146%, P<0.05) and liver (+142%, P=0.03). The protein levels of uncoupling protein-1 in brown adipose tissue and uncoupling protein-2 in liver were also increased with lipid-mobilizing factor administration (+49% and +67%, both P=0.02). Upregulation by lipid-mobilizing factor of uncoupling proteins-1, -2 and -3 in brown adipose tissue, and of uncoupling protein-2 in skeletal muscle and liver, suggests that these uncoupling proteins may serve to utilize excess lipid mobilized during fat catabolism in cancer cachexia.

Adenocarcinoma↗
PubMed2002

Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans.

The mitochondrial uncoupling proteins-2 and -3 are putative mediators of thermogenesis and energy expenditure. We measured the mRNA levels of uncoupling proteins-2 and -3 in skeletal muscle from 12 gastrointestinal adenocarcinoma patients, of whom six had stable weight and six had lost 2-18 kg, and from six healthy controls undergoing elective surgery. Uncoupling proteins-3 mRNA levels were significantly higher in the muscle of the cancer patients with weight loss (2.2 +/- 0.47 arbitrary units) compared both with controls (0.39 +/- 0.20) and with cancer patients who had not lost weight (0.47 +/- 0.23; P<0.02). Uncoupling proteins-2 mRNA levels did not differ significantly between groups. Elevations in muscle uncoupling proteins-3 activity may enhance energy expenditure and this in turn could contribute to tissue catabolism.

Adenocarcinoma↗
PubMed2002

Microsomal triglyceride transfer protein: does insulin resistance play a role in the regulation of chylomicron assembly?

We have previously demonstrated that diabetes is associated with an increase in intestinal microsomal triglyceride transfer protein (MTP) mRNA in both the rat and rabbit models. The present study was designed to investigate the relationship between MTP expression and chylomicron assembly in an insulin resistant non-diabetic animal model. Ten insulin resistant Zucker obese fa/fa rats and ten lean fa/minus sign rats were examined at 8-10 weeks of age. The lymph duct was cannulated and lymph collected for 4 h. Lymph chylomicrons were isolated by ultracentrifugation and their composition determined. RNA was extracted from intestinal mucosa and from the liver. MTP mRNA was measured using the RNase protection assay. Blood sugar in the fatty rats was significantly higher (6.3 +/-1.2 vs. 5.4 +/-0.4 P<0.05) and plasma insulin was almost six times that of the lean rats (P<0.001). Plasma cholesterol and phospholipid but not triglyceride were significantly increased in the obese animals (P<0.01). Obese animals secreted significantly more lymph chylomicron apo B48 (0.05 +/-0.02 vs. 0.02 +/-0.01 mg/h P<0.005), triglyceride (9.7 +/-5.3 vs. 3.8+/-1.9 mg/h P<0.005) and phospholipid (1.5 +/-0.7 vs. 0.4 +/-0.3 mg/h P<0.001). The only difference in the chylomicron particle composition between the two groups was a significant increase in phospholipid (P<0.01). Intestinal MTP mRNA expression was significantly higher in the fatty compared to the lean rats (22.1 +/-9.5 vs. 7.8+/-5.6 amol MTP mRNA/microg total RNA P<0.001) as was hepatic MTP mRNA expression (6.9 +/-3.5 vs. 3.4 +/-1.5 amol MTP mRNA/microg total RNA, P<0.01). Thus in this animal model of insulin resistance, increased MTP, which was associated with increased chylomicron particle number, may play a crucial role in the development of atherosclerosis.

Animals↗
PubMed2001

Design and methods of the Raloxifene Use for The Heart (RUTH) study.

Raloxifene is a selective estrogen receptor modulator that lowers total and low-density lipoprotein (LDL) cholesterol, reduces the risk of vertebral fracture, and is associated with a reduced incidence of invasive breast cancer in postmenopausal women with osteoporosis. The Raloxifene Use for The Heart (RUTH) trial is designed to determine whether raloxifene 60 mg/day compared with placebo: (1) lowers the risk of the coronary events (coronary death, nonfatal myocardial infarction [MI], or hospitalized acute coronary syndromes other than MI); and (2) reduces the risk of invasive breast cancer in women at risk for a major coronary event. RUTH is a double-blind, placebo-controlled, randomized clinical trial of 10,101 postmenopausal women aged > or =55 years from 26 countries. Women are eligible for randomization if they are postmenopausal and have documented coronary heart disease (CHD), peripheral arterial disease, or multiple risk factors for CHD. Use of estrogen within the previous 6 months is an exclusion factor. The study will be terminated after a minimum of 1,670 participants experience a primary coronary end point. Secondary end points include cardiovascular death, myocardial revascularization, noncoronary arterial revascularization, stroke, all-cause hospitalization, all-cause mortality, all breast cancers, clinical fractures, and venous thromboembolic events, in addition to the individual components of the composite primary coronary end point. RUTH will provide important information about the risk-benefit ratio of raloxifene in preventing acute coronary events and invasive breast cancer, as well as information about the natural history of CHD in women at risk of major coronary events.

Angina, Unstable↗
PubMed2001

Effect of sex hormones on cardiac mass.

Increased left-ventricular mass is an important cardiovascular risk factor for morbidity and mortality. Apart from obvious differences in cardiac size, the changes in left-ventricular mass in response to age and hypertrophic stimuli are very different in men and women. Whereas left-ventricular mass increases with age in apparently healthy women, it remains constant in men. Under increased cardiac loading conditions, such as hypertension or aortic stenosis, this disparity between sexes is even more striking. Findings are especially pronounced in people aged 50 years or older, in whom reproductive hormone concentrations have fallen. Whether the differences in left-ventricular mass changes are related to endogenous sex-hormone concentrations has never been shown. Androgens have anabolic effects on cardiac cells, and oestrogens have antiproliferative properties, we therefore postulate that the normal decline in endogenous sex hormones with age has contrary effects on ventricular mass in men and women in normal and pathological states.

Age Factors↗
PubMed2001

Topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic keratoses.

Scalp actinic keratoses (AKs) are common, particularly in elderly bald males. Cryotherapy and 5-fluorouracil are effective for localized AKs but are limited in extensive disease. Topical 5-aminolaevulinic acid photodynamic therapy (5-ALA PDT) is an alternative. We treated four patients with extensive scalp AKs with low light dose, low dose-rate topical 5-ALA PDT using a broad-spectrum visible light source. Three patients cleared and one showed significant improvement. Remission lasted 6 months.

Aged↗
PubMed2001

Reflexology and bronchial asthma.

Many asthma patients seek alternative or adjunctive therapies. One such modality is reflexology, whereby finger pressure is applied to certain parts of the body. The aim of the study was to examine the popular claim that reflexology treatment benefits bronchial asthma. Ten weeks of active or simulated (placebo) reflexology given by an experienced reflexologist, were compared in an otherwise blind, controlled trial of 20+20 outpatients with asthma. Objective lung function tests (peak flow morning and evening, and weekly spirometry at the clinic) did not change. Subjective scores (describing symptoms, beta2-inhalations and quality of life) and also bronchial sensitivity to histamine improved on both regimens, but no differences were found between groups receiving active or placebo reflexology. However, a trend in favour of reflexology became significant when a supplementary analysis of symptom diaries was carried out. It was accompanied by a significant pattern compatible with subconscious unblinding, in that patients tended to guess which treatment they had been receiving. No evidence was found that reflexology has a specific effect on asthma beyond placebo influence.

Adolescent↗
PubMed2001

Tamoxifen is not detrimental to endothelial function in postmenopausal women with breast cancer.

BACKGROUND: Tamoxifen has mixed estrogen agonist and antagonist properties in estrogen-regulated tissues. Its effect on the cardiovascular system is not well defined. We carried out a study to investigate the effect of tamoxifen on peripheral vascular endothelial function. METHODS: Three groups of postmenopausal women (median age, 56 years; range, 39 to 69 years) with breast cancer were studied. Patients in group 1 (n = 10) were newly diagnosed with breast cancer and studied before and after 4 weeks treatment with tamoxifen. Group 2 women (n = 6) had been receiving long-term tamoxifen (3 to 5 years) and were studied while taking tamoxifen and 4 weeks after stopping it. The final group of 6 subjects were in remission from primary breast cancer and were not receiving or had previously received tamoxifen. Ultrasound assessments of endothelial function were done before and 4 weeks after the initiation or discontinuation of tamoxifen with the nontreatment group acting as control. All ultrasound imaging was made by a single investigator blinded to the therapeutic status of the subject. Brachial artery diameter was measured by ultrasound at baseline and 1 minute after reactive hyperemia. Flow-mediated reactivity (FMR) was defined as percent change in artery diameter from baseline 1 minute after reactive hyperemia. RESULTS: There was no change in FMR in patients before compared with 4 weeks after starting tamoxifen (4.06% +/- 1.44% vs 3.97% +/- 1.20%, respectively, mean +/- standard error of the mean [SEM], P =.97). There was no significant change in FMR on withdrawal from tamoxifen (1.84% +/- 1.98% vs -0.42% +/- 1.44% on tamoxifen vs off tamoxifen, mean +/- SEM, P =.36). FMR in subjects taking tamoxifen was no different from the control group (3.17% +/- 1.05% vs 3.16% +/- 0.91%, respectively, mean +/- SEM, P =.995). CONCLUSIONS: Tamoxifen does not appear to affect endothelial function in the short term in postmenopausal women with breast cancer.

Adult↗
PubMed2001

Effects of storage solutions on in vitro vasoreactivity of radial artery conduits.

OBJECTIVES: Surgical preparation of coronary conduits for coronary artery bypass grafting may affect their early and long-term patency; one mechanism may involve endothelial damage. We investigated the effect of 3 commonly used solutions-Ringer's solution, normal saline solution, and heparinized whole blood-on in vitro endothelial and contractile functions of the human radial artery. METHODS: Radial artery segments were harvested, cut into 3-mm rings, and stored in unoxygenated Ringer's solution, normal saline solution, or heparinized whole blood for 45 minutes. Rings stored in Krebs solution were used as controls. The rings were then mounted and stretched to an optimal resting tension in oxygenated Krebs solution at 37 degrees C. Contraction responses to potassium, norepinephrine, and serotonin and relaxation responses to acetylcholine, verapamil, and nitroprusside were evaluated. RESULTS: Fifty-six radial artery ring segments from 14 patients (n = 7 rings for each contraction-relaxation curve) were studied. Equilibrated resting tension was 9.6 +/- 0.3 mN (5.9 +/- 0.2 g), and resting internal circumference was 6.4 +/- 0.2 mm. Absolute maximum contraction to potassium was significantly less in rings stored in normal saline solution than in rings stored in control solution (10.7 +/- 0.6 g vs 14.5 +/- 0.6 g, P <.01; 95% confidence intervals, 0.9-6.9). There was no difference in the contraction to norepinephrine (P =.11) and serotonin (P =.25) among the 3 solutions compared with the control solution. Rings stored in heparinized whole blood had significantly greater endothelium-dependent relaxation to acetylcholine (P <.007), whereas those stored in normal saline solution had reduced responses. Endothelium-independent relaxation to verapamil and nitroprusside were similar among the 3 solutions. CONCLUSION: Heparinized whole blood is a better physiologic medium for preservation of radial artery endothelial and contractile functions during storage before grafting.

Acetylcholine↗
PubMed2001

Differential effects of 6-OHDA lesions of the frontal cortex and caudate nucleus on the ability to acquire an attentional set.

Evidence from both human and animal studies indicates that catecholamine (dopamine and noradrenaline) imbalances in the fronto-striatal circuitry are associated with deficits in higher- order cognitive functions. The present study examined how catecholamines within this circuitry modulate attentional function, specifically the ability to develop, maintain, and shift an attentional set. Catecholamine depletions within the frontal cortex of the common marmoset impaired the ability to acquire an attentional set, and increased susceptibility to distraction from task-irrelevant stimuli. Analysis of set-shifting performance with stimulus dimensions of varying salience suggested that frontal catecholamine depletion selectively disrupts "top-down", but not "bottom-up" attentional processing. In contrast, the ability to acquire and shift an attentional set remained intact following dopaminergic depletion from the caudate nucleus. However, the reduced susceptibility to distraction from task-irrelevant stimuli displayed by monkeys with dopaminergic depletions of the caudate nucleus suggests that responding was under more rigid control by the currently rewarded stimulus. The results demonstrate opposite behavioural effects of 6-hydroxydopamine (6-OHDA) lesions in the frontal cortex and caudate nucleus in tasks requiring selective attention. Frontal catecholamine depletion caused an increase in distractibility while caudate dopamine loss induced greater focusing of responding.

Adrenergic Agents↗
PubMed2001

The effect of an intrauterine application of two percent lignocaine gel on pain perception during Vabra endometrial sampling: a randomised double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether two percent lignocaine gel can reduce the perception of pain during Vabra endometrial aspiration. DESIGN: Randomised, double-blind placebo-controlled trial. SETTING: Women's Health Directorate, Warrington Hospital NHS Trust. POPULATION: Women were referred to the endometrial sampling clinic for the investigation of pre and postmenopausal vaginal bleeding. METHODS: Randomisation to either pre-sampling intrauterine two percent lignocaine gel or an inert gel. Patients, recruiters and assessors were blinded to the gel used. MAIN OUTCOME MEASURES: The difference between the study groups in the proportion of women who, after Vabra sampling, recorded a pain score of > or = 6 out of 10 on a visual analogue scale. RESULTS: Three hundred and eight women were randomised, 284 (92%) completed a pain scale before and immediately after the procedure. After the procedure, 84 women (30%) recorded a pain score of > or = 6, 38 (26%) received anaesthetic and 46 (33%) an inert gel. The difference in the proportion of women recording a pain score of 6 or above between the two study groups was not significant (relative risk (RR) for the anaesthetic gel = 0.79 95% CI, 0.55, 1.14). CONCLUSIONS: Intrauterine application of 2% lignocaine gel did not significantly reduce the frequency with which women experienced unacceptable levels of pain or anxiety during endometrial aspiration compared with placebo.

Administration, Topical↗