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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 109 records · Page 6Linked to original sources
PubMed2001

Genetic analysis of case/control data using estimated haplotype frequencies: application to APOE locus variation and Alzheimer's disease.

There is growing debate over the utility of multiple locus association analyses in the identification of genomic regions harboring sequence variants that influence common complex traits such as hypertension and diabetes. Much of this debate concerns the manner in which one can use the genotypic information from individuals gathered in simple sampling frameworks, such as the case/control designs, to actually assess the association between alleles in a particular genomic region and a trait. In this paper we describe methods for testing associations between estimated haplotype frequencies derived from multilocus genotype data and disease endpoints assuming a simple case/control sampling design. These proposed methods overcome the lack of phase information usually associated with samples of unrelated individuals and provide a comprehensive way of assessing the relationship between sequence or multiple-site variation and traits and diseases within populations. We applied the proposed methods in a study of the relationship between polymorphisms within the APOE gene region and Alzheimer's disease. Cases and controls for this study were collected from the United States and France. Our results confirm the known association between the APOE locus and Alzheimer's disease, even when the epsilon 4 polymorphism is not contained in the tested haplotypes. This suggests that, in certain situations, haplotype information and linkage disequilibrium-induced associations between polymorphic loci that neighbor loci harboring functional sequence variants can be exploited to identify disease-predisposing alleles in large, freely mixing populations via estimated haplotype frequency methods.

Aged↗
PubMed2001

MAD phasing with krypton.

Experiments demonstrating the feasibility of Kr-edge MAD on frozen crystals as a routine method for structure determination are reported. Approximately 50% of protein crystals can be successfully derivatized by pressurization with the noble gases xenon or krypton. While Xe has produced many useful derivatives for MIR phasing over the last several years, the Xe edges (K edge = 34.6 keV, L(I) = 5.5 keV) are not easily accessible for MAD studies. As the Kr K edge (14.3 keV) is accessible on most MAD beamlines, Kr derivatization provides the additional opportunity to conduct a MAD experiment and obtain phases using only a single crystal. This paper describes the phasing of two proteins using Kr MAD: the 17 kDa Fe protein myoglobin (Mb) from sperm whale (Physeter catodon) and an 18 kDa protein (SP18) from green abalone (Haliotis fulgens). Three-wavelength data were collected at SSRL beamline 9-2 from crystals of Mb and SP18 incubated in 2.76 MPa of Kr gas for 2 min, depressurized and then flash-frozen in a stream of nitrogen gas at 100 K. MAD phases were calculated using the program SHARP and the resulting density improved with wARP. The final maps for both Mb and SP18 were of excellent quality.

Animals↗
PubMed2001

Psychological distress, social support, and disease activity in patients with inflammatory bowel disease.

OBJECTIVES: The objectives of this study were to compare the psychological status of patients in active and inactive disease states, to assess social support, and to identify correlates of psychological distress in patients with inflammatory bowel disease (IBD). METHODS: This cross-sectional study was conducted in 200 patients (mean age 36.7 yr [SD = 14.8], 119 [59.5%] female) with long-standing IBD who were seen in tertiary care. Psychosocial assessments included psychological distress (Symptom Checklist-90R), social support (Social Support Questionnaire-6), perceived stress (Perceived Stress Scale-10), and recent minor stressful events (Weekly Stress Inventory). Disease activity was assessed with the Harvey Bradshaw Index. RESULTS: Patients reported higher levels of satisfaction with social support and smaller network sizes compared with normative values. Using multiple linear regression, the independent correlates of psychological distress (p = 0.0001; adjusted R2 = 0.62) were as follows: active disease (p = 0.0234), less time since diagnosis (p = 0.0012), and greater number (p = 0.0001) and impact of stressful events (p = 0.0003). A statistically significant interaction term (p = 0.0171) revealed that the relationship between psychological distress and perceived stress changes depending on the level of satisfaction with social support. For patients with low levels of perceived stress, satisfaction with social support did not affect levels of psychological distress. However, for patients who experienced moderate to high levels of perceived stress, high satisfaction with social support decreased the level of psychological distress. CONCLUSIONS: These findings suggest that strategies aimed at improving social support can have a favorable impact on psychological distress and, ultimately, can improve health outcomes in patients with IBD.

Adult↗
PubMed2001

Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease.

Spinal cord injury results in a massive loss of neurons, and thus of function. We recently reported that passive transfer of autoimmune T cells directed against myelin-associated antigens provides acutely damaged spinal cords with effective neuroprotection. The therapeutic time window for the passive transfer of T cells was found to be at least 1 week. Here we show that posttraumatic T cell-based active vaccination is also neuroprotective. Immunization with myelin-associated antigens such as myelin basic protein (MBP) significantly promoted recovery after spinal cord contusion injury in the rat model. To reduce the risk of autoimmune disease while retaining the benefit of the immunization, we vaccinated the rats immediately after severe incomplete spinal cord injury with MBP-derived altered peptide ligands. Immunization with these peptides resulted in significant protection from neuronal loss and thus in a reduced extent of paralysis, assessed by an open-field behavioral test. Retrograde labeling of the rubrospinal tracts and magnetic resonance imaging supported the behavioral results. Further optimization of nonpathogenic myelin-derived peptides can be expected to lead the way to the development of an effective therapeutic vaccination protocol as a strategy for the prevention of total paralysis after incomplete spinal cord injury.

Adjuvants, Immunologic↗
PubMed2001

Successful withdrawal from analgesic abuse in a group of youngsters with chronic daily headache.

Abuse of ergotamine and analgesics is common in adults. It coexists with headache and can also induce headaches. Ten to 15% of patients attending headache clinics and 1% of the general population suffer from chronic daily headache due to medication misuse. Indeed, this phenomenon was recently regarded as an epidemic. Nonetheless, analgesic-induced headache in children and adolescents was first reported in 1998. We report on our experience with children and adolescents with daily or almost-daily headache concomitant with daily or almost-daily analgesic intake. Over a period of 3 years, we evaluated 26 children (19 girls and 7 boys) with chronic daily or near-daily headache related to daily analgesic intake. The mean age of the group was 14.2 years (range, 12-18), and the mean headache history duration was 1.6 years (range, 3 months to 4 1/2 years). The mean number of headache days per month was 28.1 (range, 19-31). All patients had no history of migraine prior to the chronic headache phase according to the International Headache Society criteria. They were using at least one dose of analgesic drug for each headache, whereas 16 were using analgesic drugs daily. The weekly analgesic intake averaged 28.1 tablets (range, 19-41). The majority abused simple analgesics. Twenty-one took acetaminophen alone. Five took a combination; four took a compound containing acetaminophen, caffeine, and codeine; and the fifth patient took a compound containing aspirin, caffeine, and codeine. All patients were informed about the phenomenon of medication-induced headache and were encouraged to achieve drug withdrawal. Withdrawal led to complete cessation of all headaches in 20 patients. In 5 patients, the daily headache resolved; however, they suffered from intermittent episodic migraine attacks, which were frequent enough in 3 to initiate prophylactic medication. One adolescent continued to have daily headache. Analgesic-induced headache does occur in adolescents. Successful withdrawal from the offending analgesics was achieved without hospitalization or significant interference with daily life and with complete disappearance of the induced chronic daily headache in 25 of 26 patients.

Adolescent↗
PubMed2001

Properties of the mammalian and yeast metal-ion transporters DCT1 and Smf1p expressed in Xenopus laevis oocytes.

Transition metals are essential for many metabolic processes, and their homeostasis is crucial for life. Metal-ion transporters play a major role in maintaining the correct concentrations of the various metal ions in living cells. Little is known about the transport mechanism of metal ions by eukaryotic cells. Some insight has been gained from studies of the mammalian transporter DCT1 and the yeast transporter Smf1p by following the uptake of various metal ions and from electrophysiological experiments using Xenopus laevis oocytes injected with RNA copies (c-RNA) of the genes for these transporters. Both transporters catalyze the proton-dependent uptake of divalent cations accompanied by a 'slippage' phenomenon of different monovalent cations unique to each transporter. Here, we further characterize the transport activity of DCT1 and Smf1p, their substrate specificity and their transport properties. We observed that Zn(2+) is not transported through the membrane of Xenopus laevis oocytes by either transporter, even though it inhibits the transport of the other metal ions and enables protons to 'slip' through the DCT1 transporter. A special construct (Smf1p-s) was made to enhance Smf1p activity in oocytes to enable electrophysiological studies of Smf1p-s-expressing cells. 54Mn(2+) uptake by Smf1p-s was measured at various holding potentials. In the absence of Na(+) and at pH 5.5, metal-ion uptake was not affected by changes in negative holding potentials. Elevating the pH of the medium to 6.5 caused metal-ion uptake to be influenced by the holding potential: ion uptake increased when the potential was lowered. Na(+) inhibited metal-ion uptake in accordance with the elevation of the holding potential. A novel clutch mechanism of ion slippage that operates via continuously variable stoichiometry between the driving-force pathway (H(+)) and the transport pathway (divalent metal ions) is proposed. The possible physiological advantages of proton slippage through DCT1 and of Na(+) slippage through Smf1p are discussed.

Animals↗
PubMed2001

Acute myopericarditis after diphtheria, tetanus, and polio vaccination.

We report the first case of myopericarditis after triple vaccination against diphtheria, tetanus, and poliovirus in a young adult. He presented with fever, acute chest pain, and diffuse ST-segment elevation 2 days after vaccination. Two-dimensional echocardiography findings were normal. Endomyocardial biopsy showed interstitial edema with diapedesis of erythrocytes. Laboratory findings showed inflammatory syndrome and elevated circulating immune complexes. He recovered within a few days with high-dose aspirin treatment and was without complications at 3-month follow-up. We discuss the different hypotheses for infective or hypersensitivity myocarditis.

Acute Disease↗
PubMed2001

Maternal epidural use and neonatal sepsis evaluation in afebrile mothers.

OBJECTIVE: Epidural use has been associated with a higher rate of neonatal sepsis evaluation. Epidural-related fever explains some of the increase but not the excess of neonatal sepsis evaluations in afebrile women METHODS: We studied 1109 women who had singleton term pregnancies and who presented in spontaneous labor and were afebrile during labor (<100.4 degrees F). Neonatal sepsis evaluation generally was performed on the basis of the presence of 1 major or 2 minor criteria. Major criteria included rupture of membranes for >24 hours or sustained fetal heart rate of >160 beats per minute. Minor criteria included a maternal temperature of 99.6 degrees F to 100.4 degrees F, rupture of membranes for 12 to 24 hours, maternal admission white blood cell count of >15 000 cells/mL(3), or an Apgar score of <7 at 5 minutes. RESULTS: Infants of afebrile women with epidural analgesia were more likely to be evaluated for sepsis than infants of women without epidural (20.4% vs 8.9%), although not more likely to have neonatal sepsis. An increased risk of sepsis evaluation persisted in regression analysis (odds ratio: 3.1; 95% confidence interval: 2.0, 4.7) after controlling for confounders and was not explained by longer labors with epidural. Women with epidural were significantly more likely to have major and minor criteria for sepsis evaluation, including fetal tachycardia (4.4% vs 0.4%), rupture of membranes for >24 hours (6.2% vs 3.4%), low-grade fever of 99.6 degrees F to 100.4 degrees F (24.3% vs 5.2%), and rupture of membranes for 12 to 24 hours (21.4% vs 5.2%) than women without epidural. CONCLUSIONS: Epidural analgesia is associated with increased rates of major and minor criteria for neonatal sepsis evaluations in afebrile women.

Adult↗
PubMed2001

[Comparative incidence of protrusive atheromatous plaques of the thoracic artery in patients with atrial fluter and atrial fibrillation].

Although it has been demonstrated recently that in patients with atrial fibrillation, protrusive atheromatous plaques of the thoracic aorta (thickness 4 mm) and left atrial abnormalities such as thrombosis, spontaneous contrast and low atrial blood flow velocities carry an additional embolic risk, this has not yet been studied in atrial flutter. Out of 2493 patients undergoing transoesophageal echocardiography between September 1993 and December 1997, 271 consecutive patients in atrial flutter (N = 41) or fibrillation (N = 230) for over 48 hours, underwent transoesophageal echocardiography before cardioversion. Patients with atrial flutter were compared with those with atrial fibrillation. Their characteristics were comparable with respect to age (68 +/- 13 and 67 +/- 12 years respectively, p = 0.628), sex ratio (men 66 and 54% respectively, p = 0.212), previous thromboembolic disease (5 and 15% respectively, p = 0.126). The incidence of protrusive aortic atheroma (12 and 11% respectively, p = 0.919), of spontaneous contrast in the thoracic aorta (15 and 14% respectively, p = 0.847) were identical in both groups. The left atrium was significantly smaller (3.1 +/- 0.7 and 6 +/- 3 cm2 respectively, p = 0.001), spontaneous atrial contrast less frequent (17 and 37% respectively, p = 0.024) and the velocities of atrial emptying higher (47 +/- 10 and 30 +/- 10 cm/s respectively, p = 0.030) in patients with flutter compared with atrial fibrillation. There was no difference in left ventricular fractional shortening (30 +/- 10 and 33 +/- 13% respectively, p = 0.630), the presence of rheumatic valvular disease (5 and 12%, p = 0.301), left atrial diameter (43 +/- 7 and 45 +/- 8, p = 0.134), right atrial surface area (16 +/- 4 and 17 +/- 6 cm2, p = 0.384) or in intraatrial thrombosis (2 and 3%, p = 0.888) respectively. These results show a high prevalence of protrusive atheroma of the thoracic aorta both in atrial flutter and in atrial fibrillation, and fewer left atrial abnormalities in patients with flutter.

Aged↗
PubMed2001

[The best in 2000 on echocardiography].

The advances in Doppler echocardiography, like last year, concern the technology, the indications and the description of the natural history of cardiovascular diseases. The year 2000 will be remembered for the development of portable echocardiographs with two-dimensional and Doppler capabilities but without M mode, pulsed or continuous Doppler. These instruments weigh less than 3 kg and may be used at the bedside; however, problems of training personnel, reimbursement and availability of equipment remain. Myocardial contrast echocardiography has been the subject of many publications which validate continuous intravenous infusion of different contrast agents, which, coupled with techniques of image processing, suggest that quantification of regional myocardial perfusion at rest or during physiological or pharmacological stress may not be far off. The indications of stress echocardiography have increased: in addition to diagnostic and prognostic information in coronary artery disease, the applications of exercise and pharmacological inotropic stress echo extend to asymptomatic valvular regurgitation to detect infraclinical myocardial dysfunction before the usual Doppler echocardiographic parameters show significant changes. The value of Doppler tissue imaging in the assessment of regional myocardial function has been demonstrated: analysis of diastolic function with pulsed Doppler at the mitral annulus, quantification of regional myocardial function in different pathologies such as ischaemic heart disease and cardiomyopathy, validation of indices during stress echocardiography with the hope of a quantitative as well as a qualitative assessment, much improved since the introduction of harmonic imaging. Finally, Doppler haemodynamic evaluation has continued to substitute for cardiac catheterisation, now providing accurate indices of quantification of valvular regurgitation and description of the natural history of cardiac diseases, especially mitral regurgitation irrespective of its cause and aortic stenosis including cases with low output states. The continuing progress of ultrasound technology is therefore confirmed and provides an outlook into the third millennium: development of portable equipment, improved probe technology, use of instruments of quantification and extension of real time three-dimensional reconstruction, systems of image stocking and transmission and better orientation of its usage with the recommendations of scientific societies.

Atrial Fibrillation↗
PubMed2001

[Atherosclerotic aortic plaques and risk of embolic stroke].

There is mounting evidence to implicate complex atherosclerotic aortic plaques as a significant independent risk factor for embolic stroke. Ulcerated plaques at autopsy, plaques thicker than 4 to 5mm at transesophageal echocardiography and those with mobile components are more likely to be associated with stroke. Mobile thrombus in the lumen may be a source of cerebral emboli. Among patients with ischemic stroke, those with plaques thicker than 4mm in the aortic arch have the highest risk of recurrent stroke, myocardial infarction, other vascular event including vascular death. However, since no randomized trials have been conducted to evaluate the role of any antithrombotic therapies in patients with aortic atheroma, no recommendation can be made regarding the best treatment strategies. Antiplatelet agents, oral anticoagulant, thrombolytic therapy, and elective surgical endarterectomy or graft replacement are all reasonable options that have been proposed and that must be evaluated in term of benefit/risks ratio in specific randomized controlled trials. Meanwhile, antiplatelet agents and aggressive risk factor management appear to be the first line treatment. No recommendation can be made to use oral anticoagulation in these patients nor for a target INR. Concerns also exist on the possibility of anticoagulation driven cholesterol embolism in these patients.

Aorta, Thoracic↗
PubMed2001

[Does Doppler analysis of hepatic venous flow predict increased right atrial pressure and right ventricular dysfunction?].

The aim of this study was to test the hypothesis that Doppler study of hepatic venous flow, reflecting right atrial pressures and right ventricular dysfunction, allows prediction of increased right atrial pressure and right ventricular dysfunction in patients with right ventricular infarction. The authors studied 30 patients (27 men, mean age 54 +/- 12 years) in sinus rhythm with acute inferior myocardial infarction who underwent right heart catheterisation and Doppler echocardiography including recording of regurgitant and hepatic vein flow within 48 hours of hospital admission. Hepatic venous flow was used to measure peak velocity and velocity time integrals (VTI) of the systolic (S), diastolic (D) and atrial (a) contraction waves. The fraction of systolic filling was calculated: VTI S/VTI S + VTI D. The pressure half-time of pulmonary regurgitant flow (PHT IP) was also measured. Using haemodynamic criteria (non-compliant right atrial pressure wave form or right ventricular end diastolic pressure/pulmonary capillary pressure > or = 0.8), patients were divided into two groups: Group 1: right ventricular infarction (VD+, N = 22). Group 2: no right ventricular infarction (VD-, N = 8). No correlation was observed between Doppler parameters of hepatic venous flow and haemodynamic data, in particular right atrial pressure and pressure wave form. Moreover, no statistically significant difference was observed between the two groups with respect to the Doppler parameters derived from hepatic venous flow. On the other hand, the results confirmed good diagnostic performance of Doppler analysis of pulmonary regurgitant flow: sensitivity 80%, specificity 83%, positive predictive value 94%, negative predictive value 55%. The authors conclude that, in patients with acute inferior wall infarction, Doppler analysis of hepatic venous flow does not allow assessment of right atrial pressure or of ischaemic right ventricular dysfunction.

Adult↗
PubMed2001

[Micronutrient (vitamins and minerals) supplementation for the elderly, suggested by a special committee nominated by Ministry of Health].

The elderly tend to be at a higher risk for nutritional deficiencies and in particular for micronutrient deficiencies. A committee nominated by Ministry of Health examined the relevant literature and the local recommendations as well as the recommendations from other countries and suggested a daily special micronutrient supplementation for institutionalized elderly. The preparatory will contain about half the RDA for most of the micronutrients, except for fluorine that is recommended at a lower level and biotin, vitamins D, C, B12 as well as zinc, copper and molybdenum at a level higher than half the RDA. Major elements such as calcium, are not included in the preparatory and would be supplied separately when needed. Vitamin K and iron are excluded as well. The suggested preparatory composition, mg: vitamin A, 0.450; vitamin D, 0.015; vitamin E, 10; thiamin, 0.6 Pound riboflavin, 0.7; biotin, 0.030; pantothenic acid, 3; niacin, 8; vitamin C, 60; vitamin B6, 0.8; folic acid, 0.120; vitamin B12, 0.0024; choline up to 275; zinc, 8; copper, 0.9; fluorine, 0.5; manganese, 1.2; chromium 0.020; molybdenum, 0.045; selenium, 0.030; and iodine, 0.075. Fat-soluble vitamins should be microencapsulated. Micronutrient supplementation is part of Ministry of Health balanced nutrition policy. The committees recommendations are also applicable for the free-living elderly.

Aged↗
PubMed2000

The family of SMF metal ion transporters in yeast cells.

Metal ions are vital for all organisms, and metal ion transporters play a crucial role in maintaining their homeostasis. The yeast (Saccharomyces cerevisiae) Smf transporters and their homologs in other organisms have a central role in the accumulation of metal ions and their distribution in different tissues and cellular organelles. In this work we generated null mutations in each individual SMF gene in yeast as well as in all combinations of the genes. Each null mutation exhibited sensitivity to metal ion chelators at different concentrations. The combination of null mutants DeltaSMF1 + DeltaSMF2 and the triple null mutant Delta3SMF failed to grow on medium buffered at pH 8 and 7.5, respectively. Addition of 5 microm copper or 25 microm manganese alleviated the growth arrest at the high pH or in the presence of the chelating agent. The transport of manganese was analyzed in the triple null mutant and in this mutant expressing each Smf protein. Although overexpression of Smf1p and Smf2p resulted in uptake that was higher than wild type cells, the expression of Smf3p gave no significant uptake above that of the triple mutant Delta3SMF. Western analysis with antibody against Smf3p indicated that this transporter does not reach the plasma membrane and may function at the Golgi or post-Golgi complexes. The iron uptake resulting from expression of Smf1p and Smf2p was analyzed in a mutant in which its iron transporters FET3 and FET4 were inactivated. Overexpression of Smf1p gave rise to a significant iron uptake that was sensitive to the sodium concentrations in the medium. We conclude that the Smf proteins play a major role in copper and manganese homeostasis and, under certain circumstances, Smf1p may function in iron transport into the cells.

Amino Acid Sequence↗
PubMed2000

Testing whether treatment is 'better' than control with ordered categorical data: an evaluation of new methodology.

A new test procedure is presented for the problem of testing whether a treatment is better than a control when there is ordered categorical data. The new test is based on the methodology developed for general 'one-sided' alternatives by Cohen and Sackrowitz. An evaluation of the test is made by comparing the power and expected p-values of the test with those of the Wilcoxon-Mann-Whitney test in examples. As predicted by the theoretical work by Cohen and Sackrowitz, the new test is seen to be preferable to the Wilcoxon-Mann-Whitney test. Computer programs to assist implementation of the new test are made available.

Data Interpretation, Statistical↗