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Biomedical subjects

D W Taylor

Publications and source records attributed to D W Taylor.

At least 55 records · Page 3Linked to original sources

Feasibility and acceptability of a proposed infant feeding intervention trial for the prevention of type I diabetes.

OBJECTIVE: To determine the feasibility of a randomized double-blind controlled trial of an infant formula without intact cow's-milk protein for preventing type I diabetes in high-risk children. RESEARCH DESIGN AND METHODS: We surveyed 83 people who either were parents of a child with type I diabetes or were pregnant women with type I diabetes in the ambulatory diabetes and obstetrics clinics in a university hospital. After a written and verbal description of the cow's milk-diabetes hypothesis, participants were asked to sign a sham consent form. A questionnaire designed to explore factors affecting their decision to either sign or not sign the consent form, as well as infant-feeding patterns, was subsequently administered. RESULTS: Overall, 69.9% (95% confidence interval, 60.0-79.8%) consented to participation in the proposed randomized trial. The decision to consent was not affected by the degree of belief in the cow's milk-diabetes hypothesis, the child's risk of diabetes, the respondent's demographic data, or infant feeding habits. CONCLUSIONS: A randomized feeding intervention study is an acceptable and feasible way to determine whether avoidance of cow's-milk protein during the first 6 months of life prevents type I diabetes in North American children.

Animals↗

Effect of recombinant human erythropoietin on hospitalization of hemodialysis patients.

The effect of recombinant human erythropoietin (EPO) on hospitalization of patients with end-stage renal disease (ESRD) was evaluated in a controlled clinical trial. A cohort of 67 new hemodialysis patients prescribed EPO shortly after the clinical availability of EPO were the treatment group. The control group was a cohort of 67 new hemodialysis patients matched for clinical center, age, cardiovascular disease and transfusion history. These patients had not been prescribed EPO as they had started hemodialysis prior to the clinical availability of EPO. There were 21 pairs without hospitalization and 46 pairs with at least 1 member of the pair experiencing hospitalization. Among the latter group, the median follow-up was 174 and 184 days for the EPO and control patients respectively. For all hospitalizations, those treated with EPO were hospitalized 15.3 days per year compared to 23.2 days for the control patients. The difference (EPO-control) was -7.9 days (95% CI: -21.0; 7.8) for all cause hospitalization. For hospitalizations due to cardiac, infectious disease and gastrointestinal disease, the differences were 1.6, 1.8 and 1.2 days favouring EPO treated patients. For hospitalizations related to vascular access complications, the difference was 0.9 days favoring the control group. All other causes favoured EPO treated patients by 4 days. There had been 58 hospitalizations in the EPO group compared to 97 in the control group. The mean duration of hospitalization was 8.0 days for the EPO and 9.6 for the control group. The direction and magnitude of the change in all cause hospitalization represents an improvement in morbidity and an important decrease in health resource utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Analysis of human T cell clones specific for conserved peptide sequences within malaria proteins. Paucity of clones responsive to intact parasites.

T cells are thought to be of central importance in malaria immunity. Peptides copying malaria protein sequences often stimulate human CD4+ T cells and it was thought that they represented T cell epitopes present in the parasite and may thus have particular relevance to malaria vaccine development. To verify whether synthetic peptides representing highly conserved regions of parasite Ags may contribute to a malaria vaccine, we searched the data bank for conserved regions of Plasmodium falciparum malaria proteins that were not homologous to known self (human) proteins. We synthesized 24 such peptides representing 11 of the cloned and sequenced malaria asexual stage Ags, which were predicted by algorithms to represent T cell epitopes, and 6 peptides not predicted to be T cell epitopes and used these to generate T cell clones from individuals with an extensive previous history of malaria exposure. The T cell clones responded vigorously to many peptides but only a single clone, specific for a peptide within merozoite surface protein-1, 20-39, VTHESYQELVKKLEALEDAV, and not previously defined to be a T cell epitope responded to malaria parasites by proliferation and secretion of IFN-gamma. This epitope was not revealed by studying parasite-induced T cell lines and is thus subdominant. The clone was able to significantly inhibit parasite growth in vitro. The final step in the inhibition of parasite growth appears to be nonspecific because other activated clones (not specific for malaria sequences) can inhibit parasite growth. Our data suggest that few conserved peptides within malaria parasites can be processed from the intact parasite. However, such peptides that can be processed from malaria parasites may be expected to stimulate parasite-specific T cells that could inhibit parasite growth and as such may be lead candidates for a vaccine aimed at inducing cellular immunity to malaria.

Adult↗

Prevention of functional impairment by endarterectomy for symptomatic high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.

OBJECTIVE: To determine whether carotid endarterectomy prevents deterioration of functional status among patients with transient ischemic attacks or nondisabling strokes and ipsilateral carotid stenosis of 70% to 99%. DESIGN: Multicentered randomized controlled trial with an average 18-month follow-up. SETTING: Fifty clinical centers in North America. PATIENTS: A total of 659 patients presenting with recent transient attacks of nondisabling stroke and ipsilateral atherosclerotic carotid stenosis of 70% to 99% were included. Patients were stable neurologically at the time of entry. No patient was lost to follow-up. INTERVENTION: Vascular surgeons and neurosurgeons were prescreened for low perioperative complication rates. Patients were randomly allocated to carotid endarterectomy plus continuing medical care (n = 328) or medical care alone (n = 331), including antiplatelet therapy. MAIN OUTCOME MEASURES: All patients were assessed by neurologists for the occurrence of stroke and functional status at scheduled intervals after entry. RESULTS: In addition to a previously reported risk reduction for ipsilateral stroke for patients assigned to carotid endarterectomy, there was an absolute risk reduction (and relative risk reduction [RRR]) for functional status impairment of 5.6% (RRR, 69%) for vision, 4.6% (RRR, 87%) for comprehension of language, 8.3% (RRR, 88%) for fluency of speech, 4.3% (RRR, 84%) for swallowing, 6.0% (RRR, 53%) for lower-limb function, 9.3% (RRR, 75%) for upper-limb function, 7.4% (RRR, 60%) for shopping, and 10.5% (RRR, 50%) for visiting outside usual residence (P < .05, two-tailed, for all items). CONCLUSIONS: Carotid endarterectomy reduced the risk for impairment of function among patients with recent symptomatic cerebral ischemia and ipsilateral high-grade carotid stenosis.

Carotid Artery, Internal↗

Molecular characterisation and localisation of an Onchocerca volvulus pi-class glutathione S-transferase.

Glutathione S-transferases (GSTs) constitute a major detoxification mechanism in helminth organisms and are regarded vaccine candidates against helminth infections. Onchocerca volvulus glutathione-binding proteins were purified from the aqueous soluble fraction of homogenised adult females by affinity chromatography on glutathione-agarose. The eluted proteins had a specific GST activity of 1.6 mumol min-1 mg-1. Immunohistochemical studies localised these antigens in the hypodermis, the wall of the seminal receptacle and spermatozoa of adult worms. A lambda gt11 clone was isolated from an expression library of O. volvulus by immunoscreening. Sequence analysis revealed that it encoded a pi-class GST with 60% identity with Caenorhabditis elegans and up to 45% identity with mammalian pi-class GSTs. Antibodies affinity selected with recombinant GST demonstrated cross-reactivity between Litomosoides sigmodontis and O. volvulus GSTs.

Amino Acid Sequence↗

Formation of two-dimensional complexes of F-actin and crosslinking proteins on lipid monolayers: demonstration of unipolar alpha-actinin-F-actin crosslinking.

A method is described for forming two-dimensional (2-D) paracrystalline complexes of F-actin and bundling/gelation proteins on positively charged lipid monolayers. These arrays facilitate detailed structural studies of protein interactions with F-actin by eliminating superposition effects present in 3-D bundles. Bundles of F-actin have been produced using the glycolytic enzymes aldolase and glyceraldehyde-3-phosphate dehydrogenase, the cytoskeletal protein erythrocyte adducin as well as smooth muscle alpha-actinin from chicken gizzard. All of the 2-D bundles formed contain F-actin with a 13/6 helical structure. F-actin-aldolase bundles have an interfilament spacing of 12.6 nm and a superlattice arrangement of actin filaments that can be explained by expression of a local twofold axis in the neighborhood of the aldolase. Well ordered F-actin-alpha-actinin 2-D bundles have an interfilament spacing of 36 nm and contain crosslinks 33 nm in length angled approximately 25-35 degrees to the filament axis. Images and optical diffraction patterns of these bundles suggest that they consist of parallel, unipolar arrays of actin filaments. This observation is consistent with an actin crosslinking function at adhesion plaques where actin filaments are bound to the cell membrane with uniform polarity.

Actinin↗

Probability of thrombosis of vascular access among hemodialysis patients treated with recombinant human erythropoietin.

The objective was to evaluate the effect of the treatment of anemia with recombinant human erythropoietin (EPO) on thrombosis of the vascular access used for hemodialysis. The research design was a prospective cohort study comparing EPO-treated hemodialysis patients with a comparison group matched for type of vascular access, clinical center, and age. All patients commencing hemodialysis in the study centers between March 1988 and July 1991 were eligible if either a graft or fistula had been used as a first permanent vascular access. There were 64 matched fistula pairs and 38 matched graft pairs. There were more patients with a history of cardiovascular disease in the EPO group than in the comparison group for both fistulae and grafts, 34 versus 14% for the former and 37 versus 5% for the latter. There was no difference between EPO and comparison groups with respect to time to first thrombosis of fistula, 11.3 versus 10.6%, respectively, by thrombosis of grafts among those treated with EPO--33.6 versus 11.2% (P = 0.02). EPO treatment does not increase the probability of fistula thrombosis, but there is an association with an increased probability of graft thrombosis.

Actuarial Analysis↗

Projection image of smooth muscle alpha-actinin from two-dimensional crystals formed on positively charged lipid layers.

Two-dimensional crystalline arrays of chicken gizzard alpha-actinin have been formed on positively charged lipid layers. This is the first reported crystallization of alpha-actinin. The crystals have unit cell dimensions of a = 248 A, b = 194 A, y = 106 degrees and contain two alpha-actinin molecules. The two-sided group is P21. Projection images obtained from electron micrographs of negatively stained crystals have been calculated to a resolution of 25 A. These images reveal a complex substructure. The molecule in projection is 340 A in length and has 12 density peaks that probably correspond to protein domains. A pair of peaks is found at each end of the molecule, these probably correspond to the actin binding region. Eight peaks are observed in the central, rod-shaped region, these may correspond to the spectrin-like repeats predicted from the amino acid sequence. However, these eight central peaks are not arranged in four pairs but, instead, consist of three central pairs flanked at either end by a single peak, which appears larger and denser in projection than the three central pairs. The individual alpha-actinin molecules in projection lack 2-fold symmetry suggesting that either smooth muscle alpha-actinin lacks a molecular 2-fold symmetry axis or that the molecular 2-fold is not parallel with the crystallographic 2-fold axis. The ends of the molecule have different appearance in projection, suggesting that the molecule is twisted about the long axis. A hypothesis is proposed to explain the variations in molecular length and Ca2+ sensitivity between alpha-actinin isoforms.

Actinin↗

Effect of high-flux hemodialysis on cardiac structure and function among patients with end-stage renal failure.

The effect of high flux hemodialysis on left ventricular function in ESRD patients was evaluated in a double blind, single cross-over, study comparing conventional to high flux hemodialysis. The subjects were 21 stable chronic hemodialysis patients. Ten were randomly allocated to the conventional-high flux sequence and 11 to the reverse sequence. The conventional membrane was the CD 3,500 or 4,000; the high flux membrane was the Duoflux (Althin Medical Inc., Miami Lakes, Fla.). Both were cellulose acetate and both were sterilized with ethylene oxide. The dialysate bicarbonate and sodium were held constant for the study. The ultrafiltration rates were 3.5-5.0 ml/h/mm Hg transmembrane pressure for the conventional and 15 ml/h/mm for the high flux membrane. The beta-2-microglobulin sieving coefficient was 0 for conventional and 0.27 for the high-flux membrane. The modest improvements in estimates of systolic function suggest a cardiac advantage in high-flux dialysis, the clinical impact of which requires further study.

Adult↗

Immunologic cross-reactivity in the pathogenesis of ocular onchocerciasis.

PURPOSE: Onchocerca volvulus, a filarial worm, is a major cause of infectious blindness and inflammatory eye disease. An autoimmune cause for ocular onchocerciasis has been suggested since the identification of a recombinant antigen of O. volvulus that shows immunologic cross-reactivity with a host ocular component of 44,000 M(r). The aim of this study was to establish the distribution of the cross-reactive antigens in both host tissues and the parasite, and to determine if significant autoantibody responses to the host antigen could be detected in infected persons. METHODS: The tissue and organ distribution of the 44,000 M(r) antigen was determined by immunocytochemistry and Western blot analysis. Human autoantibody responses to the ocular antigen were demonstrated by Western blot analysis using sera collected from persons with onchocerciasis, with and without posterior segment pathology, Bancroftian filariasis, and Europeans with no filarial infection. RESULTS: The tissue distribution of the 44,000 M(r) antigen correlates with the sites of pathology in onchocerciasis and antibody reactivity against this antigen could be detected in all persons with onchocerciasis and posterior segment pathology. The antigen is also recognized by sera from persons with Bancroftian filariasis, but not from normal persons. CONCLUSIONS: A role is proposed for immunologic cross-reactivity in the pathogenesis of onchocerciasis and it is suggested that intraocular presentation of the cross-reactive parasite antigen by microfilariae is essential for the development of disease.

Adult↗

Breast cancer in Canada: to screen or not to screen?

Lomas (1988) and Sabatier (1987) have suggested models by which to examine the roles that values, scientific knowledge, institutions, and the learning process play in the formulation of both national and clinical health-care policies. Utilizing their frameworks, this article offers an explanation for the development of high-volume screening mammography policies in Canada, despite the suggested inefficacy of screening technologies for 'unavoidable' illnesses such as carcinoma in the breast. The preliminary results of Canada's National Breast Screening Study further complicate this tissue. Inappropriate framing of the 'problem' in the policy-making process, by actors highly influenced by societal values and scientific evidence, is identified as the reason for present and planned policies and practices contradicting the first principles of health-policy analysis.

Adult↗

Canadian Hemodialysis Morbidity Study.

The objective of this study was to determine the probabilities of specific morbid events or death among patients with end-stage renal disease (ESRD) treated by hemodialysis. A prospective cohort study was performed between March 1988 and September 1989 in 18 hemodialysis centers in 13 Canadian cities, representing about one third of the hemodialysis population in Canada. The inception cohort consisted of 496 patients entering hemodialysis who had survived 1 month. The few new hemodialysis patients who received erythropoietin (EPO) in the last 3 months of the study were excluded. Survival curves were compared using the Cox proportional hazards regression model. Older age and history of cardiovascular disease were independently associated with a greater probability of death. Age and history of cardiovascular disease were also associated with a greater probability of nonfatal circulatory events (myocardial infarction, angina requiring hospitalization, or stroke), while a serum albumin level less than or equal to 30 g/L (3.0 g dL) was associated with an increased probability of pulmonary edema. The probability of surviving 12 months without receiving a blood transfusion was 47.2% for males and 27.5% for females. The incidence of non-A, non-B hepatitis, as estimated by unexplained elevations in serum aspartate aminotransferase (AST) values, was not different between patients receiving and not receiving blood transfusions. The probability of hospitalization for any cause was greater for patients with grafts for vascular access than for those with fistulae, for those with a history of cardiovascular disease, for those with a serum albumin level less than or equal to 30 g/L, and for those with renal disease due to diabetes or vascular disease. Hospitalization due to circulatory disease was more likely among those with a history of cardiovascular disease and among those with a lower serum albumin level. Hospitalization for infectious disease was more likely among those with a lower serum albumin level and less likely among those with a fistula for vascular access. Among all patients receiving hemodialysis treatment for more than 6 months, there were 14.8 hospital days per year.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Coagulation abnormalities and ivermectin.

Prothrombin ratios were measured 13-16 days after treatment in 148 subjects from Sierra Leone taking part in a double-blind placebo-controlled trial of ivermectin. Prolonged prothrombin ratios were observed more frequently in the ivermectin group, although this difference was not significant and no patients suffered bleeding complications. Further investigation of these patients failed to reveal any abnormality of liver function, although factor VII and II levels were reduced in most affected individuals, suggesting interference with vitamin K metabolism. Ivermectin has a minimal effect on coagulation and concern about mass treatment for this reason appears to be unjustified.

Adolescent↗

Development of a malaria T-cell vaccine for blood stage immunity.

We have defined a strategy for the development of a T-cell vaccine for blood stage immunity, taking into consideration the central role of T cells and MHC restriction in malaria immune responses. We have used the AMPHI computer algorithm to identify putative T-cell epitopes from conserved regions of 11 Plasmodium falciparum asexual stage proteins. Ten of the eleven proteins are currently candidates for vaccine development. Using this algorithm we selected 22 putative T-cell epitope peptides and 8 control peptides. These peptides were used to test the T-cell responses of three defined populations of Caucasians who have (1) recovered from P. falciparum malaria, (2) been exposed, but never clinically infected, (3) never been exposed or infected. Preliminary analysis of our data shows population differences in T-cell responses to putative T-cell epitope peptides. Ultimately, these studies will help to identify those T epitopes that can be incorporated into a T-cell vaccine for protective immunity.

Animals↗

Identification of anti-Plasmodium falciparum antibodies in human breast milk.

Malarial infections are rarely observed in neonates. It has been postulated that some immunity may be passively transferred during nursing, but anti-malarial antibodies (Abs) have not been detected in human milk. In this study, milk samples, collected 2-14 days after parturition from women at the Central Maternity Hospital, Yaounde, were evaluated for total IgG and IgA antibody levels by radial diffusion, protein composition by SDS-PAGE, anti-malarial antibodies using an isotype-specific immunofluorescence assay, and the ability to immunoprecipitate Plasmodium falciparum antigens metabolically labelled with 35S-methionine. Results showed that anti-P. falciparum antibodies were present in breast milk, and that paired milk and serum samples from individual women contained Abs that recognized similar malarial antigens.

Adolescent↗

Effect of high-flux hemodialysis on quality of life and neuropsychological function in chronic hemodialysis patients.

The objective was to evaluate the effect of high-flux hemodialysis on quality of life, intra- and interdialytic symptoms and neuropsychological function. The study was double-blind single cross-over with random allocation to order of treatment. The patients were stable adult hospital hemodialysis patients. Both the conventional and high-flux membranes were cellulose acetate, the dialysate was bicarbonate, and dialysate sodium was held constant. The high-flux membrane had an ultrafiltration rate of 15 ml/h/mm Hg transmembrane pressure, a B12 clearance of 88 ml/min and a beta 2-microglobulin clearance of 11.4 ml/min. The values of the conventional membrane were 3.5-5.0, 34-45 and negligible. Each treatment period was 4 months. Twenty-two patients completed both phases of the cross-over. The KT/V value was higher during high-flux than conventional treatment; 1.42 versus 1.27(p < 0.05). There were no differences between high-flux and conventional treatment with respect to quality of life. Symptoms during dialysis were less severe during high-flux than conventional treatment for 12/14 items. Only 3 items reached statistical significance (0.05 > p > 0.01) and none were clinically significant. Symptoms between dialyses were less severe during high-flux than conventional treatment for 18/20 items. No single item had a statistically significant improvement but 3 had clinically important improvement. Among the 23 neuropsychological variables, none demonstrated statistically significant changes.

Adolescent↗