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Biomedical subjects

R Collins

Publications and source records attributed to R Collins.

At least 91 records · Page 5Linked to original sources
PubMed1997

Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies.

OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.

Cholesterol, Dietary↗
PubMed1997

Decreased insulin content and secretion in RIN 1046-38 cells overexpressing alpha 2-adrenergic receptors.

Several Gi-protein-coupled receptors normally expressed in islet beta-cells inhibit insulin secretion on binding of their respective agonists. To study the effect of supraphysiologic expression of such a receptor in insulin-secreting beta-cells, we stably transfected cDNA encoding the mouse alpha 2a-adrenergic receptor into RIN 1046-38 cells. Four different cell lines were selected, each overexpressing the alpha 2a-adrenergic receptor to varying degrees. Cell lines showing the highest level of receptor expression showed significantly reduced insulin content, and reduced basal and stimulated insulin secretion. Pertussis toxin (PTX) treatment of cells was able to reverse partially the reduced insulin secretory response. Our results suggest that overexpression of a Gi-protein-coupled receptor in beta-cells causes tonic inhibition of both insulin synthesis and secretion. Abnormalities in expression or function of such receptors could be a contributory factor in the impaired insulin secretion present in type II diabetes.

Animals↗
PubMed1997

Down syndrome and neural tube defect screening: the value of using gestational age by ultrasonography.

OBJECTIVE: Our goal was to determine whether gestational age should be based on ultrasonographic evaluation or last menstrual period data in the interpretation of second-trimester maternal serum screening for Down syndrome and open neural tube defects. STUDY DESIGN: Initial and revised screen-positive rates and detection rates were reviewed for women undergoing triple-marker testing (maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol). The study population consisted of > 24,000 women at 15.0 to 21.9 weeks' gestation with approximately 60% of test interpretations based on ultrasonographic evaluation of gestational age. Gestational age and screening results were compared for 24 Down syndrome pregnancies in which both ultrasonography and last menstrual period dating were available. RESULTS: Both initial and revised screen-positive rates for Down syndrome were significantly lower when ultrasonographic data were used compared with last menstrual period dating. The detection rate for Down syndrome appeared to be higher with ultrasonographic dating (approximately 76% vs 60% for last menstrual period dating). Down syndrome fetuses had a significantly shorter gestational age when evaluated by ultrasonography (relative to last menstrual period dating), but a similar trend was also seen in control pregnancies. Initial and revised screen-positive rates for open neural tube defects were higher for women who had received an ultrasonographic examination compared with the rates for those women referred with only last menstrual period data. The detection rates for open neural tube defects were similar for both methods of pregnancy dating. CONCLUSION: By use of ultrasonographic measurement of gestational age, the number of amniocenteses performed to detect Down syndrome can be substantially reduced while detection rates are maintained or improved.

Adult↗
PubMed1997

Randomized placebo-controlled study of the effects of simvastatin on haemostatic variables, lipoproteins and free fatty acids. The Oxford Cholesterol Study Group.

The Oxford Cholesterol Study is a randomized placebo-controlled trial designed primarily to assess the effects of simvastatin on blood cholesterol levels and side-effects in preparation for a large, long-term trial of the effects of cholesterol-lowering drug therapy on mortality. At present there is only limited evidence from randomized comparisons of the effects of HMG-CoA reductase inhibitors, such as simvastatin, on thrombogenic, as distinct from atherogenic, pathways in coronary heart disease. The present sub-study was carried out to assess the effects of simvastatin on a range of haemostatic variables, as well as on free fatty acids and on lipoprotein fractions not studied in detail previously. At an average of about 2 years after starting study treatment, non-fasting blood samples were obtained from a sequential sample of 162 participants who had been randomly allocated to receive 40 mg (54 patients) or 20 mg (57 patients) daily simvastatin or matching placebo treatment (51 patients). Only patients who reported taking their study treatment and who were not known to be diabetic or to be taking some other lipid lowering treatment were to be included. The principal comparisons were to be of those allocated simvastatin (i.e. 20 and 40 mg doses combined) vs those allocated placebo. Among patients allocated simvastatin, marginally significant lower factor VII antigen levels (12.10% +/- 6.08 of standard; 2P < 0.05) and non-significantly lower factor VII coagulant activity (8.24% +/- 4.99 of standard) and fibrinogen concentrations (0.10 +/- 0.08 g. l-1) were observed. In contrast, plasminogen activator inhibitor activity was significantly higher (2.62 +/- 1.03 IU; 2P < 0.01) among patients allocated simvastatin. No significant differences were seen in the other haemostatic factors studied (e.g. prothrombin fragment 1.2, factor XII and C1 inhibitor). Total free fatty acid concentration was marginally significantly reduced (2P = 0.02) with simvastatin, but none of the reductions in individual free fatty acids was significant. Lipoprotein fractions were only measured among patients allocated 40 mg daily simvastatin or placebo. Compared with placebo, simvastatin produced significant decreases not only in LDL cholesterol (1.74 +/- 0.15 mmol.1(-1): 2P < 0.0001) but also in VLDL cholesterol (0.28 +/- 0.08 mmol.1(-1); 2P < 0.001) and IDL cholesterol (0.17 +/- 0.03 mmol.1(-1); 2P < 0.0001). There were also lower triglyceride levels associated with LDL (0.07 +/- 0.01 mmol.1(-1); 2P < 0.0001), IDL (0.03 +/- 0.01 mmol.1(-1); 2P < 0.01) and VLDL (0.27 +/- 0.14; 2P = 0.05). The effects of simvastatin on haemostatic variables appear to be far less marked than its lipid effects. Given the associations of haemostatic factors with coronary heart disease incidence, larger randomized comparisons of the HMG-CoA reductase inhibitors (and of the newer fibrates which may produce greater effects) are needed to provide more reliable estimates of the extent to which they influence these variables.

Adult↗
PubMed1997

N-linked glycosylation of the human Ca2+ receptor is essential for its expression at the cell surface.

The human Ca2+ receptor (hCaR) is a member of the superfamily of G protein-coupled receptors. Its large (approximately 600 residue) amino-terminal extracellular domain contains 9 potential N-linked glycosylation sites. Immunoblot of cell membranes derived from HEK-293 cells, stably transfected with the hCaR, showed two major immunoreactive bands of approximately 150 and 130 kDa, respectively. Complete digestion of the membranes with PN-glycosidase F yielded a single major immunoreactive band of approximately 115 kDa, confirming the presence of N-linked glycosylation. Treatment of these cells with tunicamycin, which blocks N-linked glycosylation, inhibited signal transduction in response to Ca2+. Flow cytometric analysis showed decreased expression of the hCaR on the cell membrane in tunicamycin-treated cells. Immunoblot of tunicamycin-treated cells showed a reduction in the amount of the 150-kDa band and conversion of the 130-kDa band to the presumptively nonglycosylated 115-kDa form. Tunicamycin treatment of cells, transfected with a mutant hCaR complementary DNA containing a nonsense codon at position 599 preceding the 1st transmembrane domain, blocked the secretion of a 95-kDa protein, representing the amino-terminal extracellular domain, into the medium. These results demonstrate that N-linked glycosylation is required for normal expression of the hCaR at the cell surface.

Calcium↗
PubMed1997

Protozoan parasites of the intestinal tract: a review of Coccidia and Microsporida.

Ubiquitous in nature, members of the Coccidia and Microsporida are being reported with increasing frequency in the immunocompromised as well as the immunocompetent population. These protozoans are primarily waterborne, but foodborne disease has also been reported. These organisms are responsible for acute, as well as protracted, cases of watery diarrhea with various other related sequelae. The Coccidia includes three genera--Cryptospridium, Isospora, and Cyclospora. The latter two are of lesser importance in terms of morbidity and mortality. The Microsporida includes genera (Enterocytozoon, Encephalitozoon) only recently recognized as important agents of disease. Unlike the Coccidia, these organisms are more restricted to the immunocompromised population. Increased incidence and numbers of patients with prolonged diarrhea due to these forms indicate the need for increased clinical vigilance with regard to prevention, diagnosis, and treatment.

Animals↗
PubMed1997

Medians for second-trimester maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol; differences between races or ethnic groups.

Second-trimester maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are routinely measured in screening fetuses at high risk for Down syndrome or open neural tube defects (ONTD). For test interpretation, individual patient values of these three analytes are related to population-derived median values. We evaluated data from >21000 pregnancies to determine the extent of race-specific differences in median concentrations. For samples at most gestational ages, median AFP, hCG, and uE3 values for white, black, Hispanic, and other patients were all significantly different. Differences remained significant even when data were corrected for patient weights. For each analyte, the extent of the variation was not the same at different gestational ages. Differences in median values across race/ethnicity groups appear to have only a small impact in Down syndrome screening but it may be appropriate to use alternative sets of AFP medians or adjustment factors to AFP medians for some Asian populations receiving ONTD screening.

Black People↗
PubMed1997

Controlled diffusional release of dispersed solute drugs from biodegradable implants of various geometries.

Chronic diseases and pathological medical conditions requiring the administration of longterm pharmaceutical dosages have in the past been treated by oral administrations of tablets, pills and capsules or through the use of creams and ointments, suppositories, aerosols, and injectables. Such forms of drug delivery, which are still currently used today, provide a prompt release of the drug, but with significant fluctuations in the drug levels within various regions of the body. Repeated administrations of the drug are often needed, at rather precise intervals of time, in order to maintain these levels within a relatively narrow therapeutic range as a means of assuring effectiveness at the low end and of minimizing adverse effects at the higher end of the fluctuation spectrum. Recent technical advances now permit one to control the rate of drug delivery. The required therapeutic levels may thus be maintained over long periods of months and years through implanted rate-controlled drug release capsules. Two such novel drug delivery systems currently employed are implanted erodible polymeric and ceramic capsules. Mathematical modeling and computer simulations can be very effective in improving and optimizing the performance of the self-regulating release of therapeutic drugs into specific regions of the body. Further development is needed for the optimal design of such capsules. It is in this area, in particular, that a review will be presented of the mathematical modeling techniques susceptible to refine the development of a reliable tool for designing and predicting the resulting pharmaceutical dosages as a function of time and space. Of primary importance in such models are the time-varying effective permeability of the capsule to the various molecules composing the drug, the effective solubility and diffusion coefficients of the drug and its metabolites in the surrounding tissues and fluids and, finally, the uptake of the drug at the target organ. Mathematical models are presented for the diffusional release of a solute from an erodible matrix in which the initial drug loading c0 is greater than the solubility limit cs. An inward moving diffusional front separates the reservoir (unextracted region) containing the undissolved drug from the partially extracted region. The mathematical formulation of such moving boundary problems has wide application to heat transfer with melting phase transitions and diffusion-controlled growth of particles, in addition to our topic of controlled-release drug delivery. In spite of this diversity of applications, only a very few mathematical descriptions have been published for the analysis of release kinetics of a dispersed solute from polymeric or ceramic matrices. In these rare instances, perfect sink conditions are assumed, while matrix swelling, concentration-dependence of the solute diffusion coefficient and the external mass transfer resistance have been largely neglected. The ultimate goal of such an investigation is to provide a reliable design tool for the fabrication of specialized implantable capsule/drug combinations which will deliver pre-specified and reproducible dosages over a wide spectrum of conditions and required durations of therapeutic treatment. Such a mathematical/computational tool can also prove effective in the prediction of suitable dosages for other drugs of differing chemical and molecular properties which have not been subjected to time-consuming animal laboratory testing. Finally, such models may permit more realistic scaling of the required dosages of therapeutic drug for variations in diverse factors such as body weight or organ size and capacity of the patient (clinical medicine) or animal (veterinary medicine for farm animals). Additional applications of controlled-release drug delivery for insecticide and pesticide use in agriculture, and the control of pollution in lakes, rivers, marshes, etc. in which a pre-programmed dose-time schedule is necessary, further

Biocompatible Materials↗
PubMed1997

Review of major injuries and fatalities in USAF ejections, 1981-1995.

Our laboratories are examining injuries and deaths resulting from mechanical forces applied to aircrew members in the course of Department of Defense aviation operations. In this paper we report only on bodily injuries sustained during ejection from US Air force, aircraft for the fiscal years 1981-1996, that is, major injuries and fatalities resulting directly from seat acceleration forces, from aerodynamic forces applied to crew members during escape through the effects of windblast and parachute opening shock; from direct contact: and from parachute landing injuries. Such injuries occur typically to the head, neck, cervical spine, thorax, thoracolumbar spine, ribs, pelvis, and the upper and lower extremities. Injuries are usually caused by anomalies in the ejection sequence or by delaying ejection until too close to the ground. Conversely, a planned ejection in a modern ejection seat in controlled, low speed flight imposes forces well below injury thresholds. In the USAF, 10-50 aircrew eject yearly, with a decline since 1991. We conclude that the risk of fatality is 0-11% and of major injury is 2-25%. Both are remarkably low and decreasing in the later years of this study period. The absolute number of head, neck, and spine injuries is 0-10 yearly and similarly decreasing. The results of this study are intended to provide a basis for estimating potential savings in deaths, injuries, and costs expected from the development of improved protective measures.

Accidents, Aviation↗
PubMed1996

Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.

OBJECTIVES: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. DESIGN: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. SUBJECTS: Patients with suspected acute myocardial infarction. INTERVENTIONS: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68,000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. MAIN OUTCOME MEASUREMENTS: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). RESULTS: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P < 0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were seen with the different anticoagulant regimens studied. In the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% to 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. There were 3 (1.3) fewer reinfarctions per 1000 (2P = 0.04) and 1 (0.5) fewer pulmonary emboli per 1000 (2P = 0.01), but there was a small non-significant excess of stroke and a definite excess of 3 (1) major bleeds per 1000 (2P < 0.0001). CONCLUSIONS: The clinical evidence from randomised trials dose not justify the routine addition of either intravenous or subcutaneous heparin to aspirin in the treatment of acute myocardial infarction (irrespective of whether any type of fibrinolytic therapy is used).

Anticoagulants↗
PubMed1996

A C-terminal mutant of the G protein beta subunit deficient in the activation of phospholipase C-beta.

The molecular mechanism by which the G protein betagamma complex modulates multiple mammalian effector pathways is unknown. Homolog-scanning mutagenesis of the G protein beta subunit was employed to identify residues critical for the activation of phospholipase C-beta2 (PLC-beta2). A series of chimeras was made by introducing small segments of the Dictyostelium beta subunit into a background of mammalian beta1 and tested in COS cell cotransfection assays for their ability to activate PLC-beta2 and assemble with mammalian gamma2. A chimera that contained four Dictyostelium beta substitutions within the C-terminal 14 residues was unable to activate PLC-beta2 when cotransfected with gamma, despite its demonstrable expression in a gamma-dependent manner. Cotransfection of the mutant blocked m2 muscarinic receptor activation of PLC by a pertussis toxin-sensitive pathway. This C-terminal mutant retained the ability, however, to stimulate the mitogen-activated protein kinase pathway. These results imply that activation of different betagamma-responsive effectors is mediated by distinct domains.

Amino Acid Sequence↗
PubMed1996

Randomised placebo controlled trial of effect on mood of lowering cholesterol concentration. Oxford Cholesterol Study Group.

OBJECTIVE: To evaluate the effects on mood of a substantial and prolonged reduction in total cholesterol concentration. DESIGN: Randomised placebo controlled comparison of patients who had been allocated to receive simvastatin 20 mg or 40 mg daily versus those allocated matching placebo in a ratio of 2:1. Follow up at an average of 152 weeks after randomisation. SUBJECTS: Men and women aged between 40 and 75 years at entry with blood total cholesterol of 3.5 mmol/l or greater, who were considered to be at higher than average risk of coronary heart disease based on medical history. MAIN OUTCOME MEASURES: The shortened profile of mood states questionnaire, reported use of psychotropic medication, and symptoms possibly related to mood. RESULTS: Simvastatin reduced total cholesterol by 1.9 mmol/l (26.7%) at the time of follow up. Among all 621 patients randomised to simvastatin (414 patients) or placebo (207 patients) there were no significant differences in the use of psychotropic medication or in reports of symptoms possibly related to mood. Of these patients, 491 (334 simvastatin, 157 placebo) completed the mood questionnaire, and there were no significant differences between the treatment groups in total or subscale scores, even when patients with low baseline cholesterol concentrations or elderly subjects were considered separately. CONCLUSION: These results do not support the hypothesis that treatment to lower cholesterol concentration causes mood disturbance.

Adult↗