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Biomedical subjects

P Collins

Publications and source records attributed to P Collins.

At least 109 records · Page 6Linked to original sources

Hormone and nonhormone therapy for the maintenance of postmenopausal health: the need for randomized controlled trials of estrogen and raloxifene.

Multiple health benefits have been postulated for the long-term use of hormone therapy in postmenopausal women, most notably for prevention of osteoporotic fractures and coronary heart disease, as well as several risks, including cancer of the breast and uterus and venous thromboembolism. Cardiovascular disease is the most common cause of death among postmenopausal women. If real, the reduction in risk of coronary heart disease by hormone use suggested by observational studies would likely outweigh the risks. The decision to initiate and maintain hormone therapy is complicated by uncertainties about estrogen's true benefits and risks. Raloxifene, a selective estrogen receptor modulator (SERM), appears to have many of the benefits of estrogen without the cancer risks. It is not known if SERMs can provide significant cardiovascular protection. This article reviews the relation of use of postmenopausal hormones and raloxifene to women's health and addresses the need for large randomized trials to quantify the effect of both postmenopausal estrogen and raloxifene on cardiovascular health.

Cardiovascular Diseases↗

Antibodies to oxidized lipoproteins and their relationship to myocardial infarction.

The inflammatory process and autoimmunity in the form of antibodies to oxidized LDL are important factors in the formation of the atherosclerotic plaque. We examined the time relationship of oxidized lipoprotein antibodies to the acute oxidative stress of myocardial infarction (MI). We also examined the relationship of C-reactive protein, an index of inflammation, and therefore of free radical production, to oxidized low-density lipoprotein (LDL) antibodies. We examined five groups of patients in a cross-sectional study: group 1, within 48 h of MI; group 2, two days to 1 week; group 3, 1-4 weeks; group 4, 1-3 months; and group 5, 3-6 months post MI. Nine patients with high antibody levels were re-examined 12 months after their first assessment. Malondialdehyde (MDA)-LDL and MDA-HDL antibodies were determined by an ELISA method. The highest MDA-LDL antibodies were found within 48 h of MI, but there was no significant difference in MDA-HDL antibodies between the groups. When 9/10 patients with LDL antibodies greater than the mean of 2.7 were re-examined 1 year later, there was a significant decrease in the mean antibody levels (5.2 +/- 1.7 vs. 3.2 +/- 0.6, p < 0.02). There was no correlation between antibodies to MDA-LDL and antibodies to MDA-HDL. There was a positive correlation between serum HDL cholesterol and antibodies to MDA-LDL (r = 0.4, p < 0.02) and a positive correlation between serum triglycerides and MDA-HDL antibodies (r = 0.39, p < 0.02). Acute MI appears to be associated with significantly higher C-reactive protein and antibodies to MDA-LDL, suggesting a possible acceleration of the atherosclerotic process immediately prior to MI.

Aged↗

Survey of resistance of herpes simplex virus to acyclovir in northwest England.

Acyclovir (ACV) has been used for more than 15 years in the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) disease. The present survey was undertaken to assess the level of ACV resistance in the population. More than 2,000 HSV isolates from both immunocompetent and immunocompromised patients in northwest England were collected over a 2-year period and tested for sensitivity to ACV. These studies suggested a prevalence of resistance of approximately 0.1 to 0.6% in immunocompetent individuals, with no apparent difference in prevalence between treated and untreated groups. In line with previous studies, the prevalence of resistance in treated immunocompromised individuals was approximately 6%.

Acyclovir↗

Perseveration and strategy in a novel spatial self-ordered sequencing task for nonhuman primates: effects of excitotoxic lesions and dopamine depletions of the prefrontal cortex.

Damage to the prefrontal cortex disrupts the performance of self-ordered sequencing tasks, although the precise mechanisms by which this effect occurs is unclear. Active working memory, inhibitory control, and the ability to generate and perform a sequence of responses are all putative cognitive abilities that may be responsible for the impaired performance that results from disruption of prefrontal processing. In addition, the neurochemical substrates underlying prefrontal cognitive function are not well understood, although active working memory appears to depend upon an intact mesocortical dopamine system. The present experiments were therefore designed to evaluate explicitly the contribution of each of these abilities to successful performance of a novel spatial self-ordered sequencing task and to examine the contribution of the prefrontal cortex and its dopamine innervation to each ability in turn. Excitotoxic lesions of the prefrontal cortex of the common marmoset profoundly impaired the performance of the self-ordered sequencing task and induced robust perseverative responding. Task manipulations that precluded perseveration ameliorated the effect of this lesion and revealed that the ability to generate and perform sequences of responses was unaffected by excitotoxic damage to prefrontal cortex. In contrast, large dopamine and noradrenaline depletions within the same areas of prefrontal cortex had no effect on any aspect of the self-ordered task but did impair the acquisition of an active working memory task, spatial delayed response, to the same degree as the excitotoxic lesion. These results demonstrate that a lesion of the ascending monoamine projections to the prefrontal cortex is not always synonymous with a lesion of the prefrontal cortex itself and thereby challenge existing concepts concerning the neuromodulation of prefrontal cognitive function.

Animals↗

Risky business. It takes a 'risk-balanced' team to implement a CPR.

UNLABELLED: University of Colorado Hospital: 393-bed inpatient facility and 30 clinics. PROBLEM: A breakdown of collecting and exchanging clinical information. SOLUTION: Create a computer-based patient record project development team to select and implement a CPR system. RESULTS: Eight clinics now participate in the system. KEYS TO SUCCESS: "Creating a risk-balanced team and a strong, honest vendor partnership."

Colorado↗

Oral health-related quality of life: a model for dental hygiene.

During the past decade, dental hygiene has been challenged to develop conceptual models to define the discipline. Such models can provide a common language and infrastructure for the discipline to define the process of care. Health-Related Quality of Life conceptual models have been adopted by many health professions to assist in planning health-related interventions and assessing outcomes to care. Based on the Natural History of Disease Schema, the Wilson & Cleary model, and Neuman's Systems Model, a new conceptual model for dental hygiene is proposed. The Oral Health-Related Quality of Life Model, composed of six primary domains: Health/Preclinical Disease, Biological/Clinical Disease, Symptom Status, Functional Status, Health Perceptions, and General Quality of Life. This model proposes a dynamic relationship among these domains and characteristics unique to individual clients or populations, and may have utility for interdisciplinary communication. As an integrated model, it may serve as a foundation for assessing, planning, implementing, and evaluating outcomes to dental hygiene care. This paper reviews possible application of the model for clinical practice, research, and education.

Dental Hygienists↗

Short-term anti-ischemic effect of 17beta-estradiol in postmenopausal women with coronary artery disease.

BACKGROUND: Short-term administration of 17beta-estradiol improves effort-induced myocardial ischemia in female patients with coronary artery disease. 17Beta-estradiol also has direct and indirect coronary vascular smooth muscle relaxing properties. The aim of the present study was to evaluate the effect of short-term administration of 17beta-estradiol on pacing-induced myocardial ischemia by means of continuous monitoring of coronary sinus pH in 16 postmenopausal female patients with coronary artery disease. METHODS AND RESULTS: Patients underwent incremental atrial pacing starting at a rate of 100 bpm and increments of 20 bpm every 2 minutes up to 160 bpm before and 20 minutes after either 17beta-estradiol (1 mg sublingual, 9 patients) or placebo (sublingual, 7 patients). The time to the onset of myocardial ischemia during pacing was significantly increased by 17beta-estradiol (mean+/-SD, 254+/-36 versus 298+/-23 seconds; P<.02) but not by placebo (262+/-45 versus 256+/-34 seconds; P=NS) The pH shift was significantly reduced by 17beta-estradiol but not by placebo at every step of the pacing protocol. The maximum pH shift at peak pacing was significantly reduced by the administration of 17beta-estradiol by 0.022 pH units (95% CI, 0.001, 0.043; P<.04) but not by sublingual placebo (-0.002 pH units; 95% CI, -0.0073, 0.0021; P=NS). The maximum pH shift at maximum comparable pacing was also reduced by 17beta-estradiol by 0.015 pH units (95% CI, 0.012, 0.017; P<.001) but not by placebo (-0.0022 pH units; 95% CI, -0.006, 0.0015; P=NS). CONCLUSIONS: 17Beta-estradiol reduces the degree of pacing-induced myocardial ischemia in postmenopausal patients with coronary artery disease. The reduction of pacing-induced coronary sinus pH shift is consistent with an anti-ischemic effect of the hormone and is not due to preconditioning, as evidenced by the absence of improvement after placebo.

Cardiac Pacing, Artificial↗

Production of the novel C-C chemokine MCP-4 by airway cells and comparison of its biological activity to other C-C chemokines.

Monocyte chemotactic protein-4 (MCP-4) is a newly identified C-C chemokine with potent eosinophil chemoattractant properties. We describe studies of its biological activity in vitro to induce chemotaxis of peripheral blood eosinophils and to induce histamine release from IL-3-primed peripheral blood basophils. MCP-4 and eotaxin caused a similar rise in eosinophil intracytoplasmic Ca2+ and complete cross-desensitization. MCP-4 also abolished the eosinophil Ca2+ response to MCP-3 and partially desensitized the response to macrophage inflammatory protein-1alpha. MCP-4 activated cell migration via either CCR2b or CCR3 in mouse lymphoma cells transfected with these chemokine receptors. MCP-4 inhibited binding of 125I-eotaxin to eosinophils and CCR3-transfected cells and inhibited 125I-MCP-1 binding to CCR2b-transfectants. MCP-4 mRNA was found in cells collected in bronchoalveolar lavage of asthmatic and nonasthmatic subjects and was prominently expressed in human lung and heart. MCP-4 mRNA was expressed in several human bronchial epithelial cell lines after cytokine stimulation. Pretreatment of BEAS-2B epithelial cells with the glucocorticoid budesonide inhibited MCP-4 mRNA expression. These features make MCP-4 a candidate for playing a role in eosinophil recruitment during allergic respiratory diseases.

Amino Acid Sequence↗

The role of dietary cholesterol in the regulation of postprandial apolipoprotein B48 levels in diabetes.

The atherogenicity of intestinally derived postprandial lipoproteins has been confirmed in a number of recent studies. We have shown abnormalities in postprandial lipoprotein metabolism in diabetic patients, a group with an increased susceptibility to atherosclerosis. This study examined the relationship between dietary cholesterol and the postprandial, intestinally derived, apolipoprotein B48 and apolipoprotein B100 from the liver. We compared 10 non-insulin-dependent (Type 2, NIDDM) diabetic patients and 10 age-matched non-diabetic control subjects. Fasting blood was taken and subjects were fed a cholesterol-free, high fat meal. Blood samples were repeated at 2 h, 4 h, 6 h, and 8 h postprandial. The following week fasting blood was collected and subjects were given the same meal with 1 g of added cholesterol. Blood was collected at the same time points. Chylomicrons and very low density lipoprotein were isolated by sequential ultracentrifugation and their lipoprotein composition determined. Apolipoproteins B48 and B100 were separated by gradient gel electrophoresis and quantified by densitometric scanning using a low density lipoprotein apolipoprotein B100 standard. Post prandial chylomicron cholesterol and triglyceride increased after the high cholesterol meal in both groups (p < 0.001). The postprandial chylomicron apolipoprotein B48 response of both diabetic and control subjects to the cholesterol meal was less than to the cholesterol-free meal (p < 0.001). Fasting very low density lipoprotein apolipoprotein B48 was higher in diabetic patients compared to control subjects and their postprandial increase following the cholesterol-free meal was significantly greater (p < 0.001). There was a 10-fold increase in the incremental postprandial VLDL apolipoprotein B48 area under the curve after the cholesterol-rich meal in the diabetic patients compared to a 3-fold increase in control subjects. The postprandial very low density lipoprotein apolipoprotein B100 was similar in the two groups with both meals. The study demonstrates a very significant increase in the amount of intestinally derived small apolipoprotein B48-associated particles in the very low density lipoprotein fraction following a cholesterol-rich meal in diabetic patients. Synthesis rather than clearance may be the major cause of the increase in these atherogenic postprandial particles.

Aged↗

The effect of fenfluramine dosage regimen and reduced food intake on levels of 5-HT in rat brain.

Male Wistar rats received fenfluramine in subacute (5 mg/kg b.i.d. i.p. for 4 days) or escalating (0.5, 1, 1.5, 2, 3, 4 and 5 mg/kg b.i.d. i.p., each dose given for 4 days) doses. Saline-treated controls received food ad libitum, or were pair-fed with the fenfluramine-treated animals. Rats were killed 1, 15 and 30 days after drug withdrawal. On day 1, plasma and brain fenfluramine levels were higher, and hypothalamus norfenfluramine levels were lower following escalating compared to subacute dosing, although total active drug levels were unaltered. Both treatment regimes, and pair-feeding reduced food intake and body weight. Subacute fenfluramine reduced brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels for up to 30 days. Brain 5-HT and 5-HIAA levels were unaltered following escalating-doses of fenfluramine. Additionally, pair-feeding transiently decreased hippocampal 5-HT levels. These data suggest that escalating-doses of fenfluramine prevent the 5-HT-depleting effect of a sub-cute challenge without altering the anorexic action of the drug.

Animals↗

Successful engraftment of haploidentical stem cell transplant for familial haemophagocytic lymphohistiocytosis using both bone marrow and peripheral blood stem cells.

Familial haemophagocytic lymphohistiocytosis (HLH) is a disease with a very poor prognosis unless patients receive a bone marrow transplant. It is often difficult to find an HLA-matched donor and haploidentical familial donors may be considered. The main complication of this type of transplant is graft rejection. We describe a patient with familial HLH who received a haploidentical transplant using both mobilized peripheral blood and bone marrow stem cells in an attempt to overcome graft rejection by increasing the stem cell dose. The peripheral blood stem cell inoculum was CD34 enriched using a Cellpro column and T-cell depleted by Campath-1M, the patient received conditioning for a matched sibling donor transplant with the addition of Campath 1G. There was rapid and full engraftment and the patient remains disease free at 5 months. This technique may be applicable for other fatal inborn errors in the absence of an HLA-matched donor.

Bone Marrow Transplantation↗