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Biomedical subjects

F White

Publications and source records attributed to F White.

At least 37 records · Page 2Linked to original sources

Evaluating programs to prevent unintentional trauma in Canada: challenges and directions.

BACKGROUND: Trauma remains the number one cause of death for people under the age of 44 years and consumes a disproportionate amount of resources. This review describes the spectrum of prevention strategies in Canada, current behavior-oriented trauma prevention initiatives, and evaluations of their effectiveness. METHODS: A literature search of English language citations in MEDLINE was carried out by using the word "prevention" in conjunction with any of the words "injury," "accident," "trauma," "fall," "collision," and "traffic." Relevant material from bibliographies was also obtained. A comprehensive compilation of local and national prevention programs in Canada was reviewed. Only programs with reported evaluation data were included. CONCLUSION: Enforcing trauma prevention measures through legislation seems to be the most effective strategy. Educational models have not been adequately evaluated because of methodologic and economic constraints. New prevention initiatives must be supported with more resources and evaluation strategies. Involvement of health care professionals in prevention is encouraged.

Accident Prevention↗

Status of national diabetes programmes in the Americas.

Reported are the responses in the latter half of 1997 of all ministries of health in the Region of the Americas to the Declaration of the Americas on Diabetes, which was adopted by the Directing Council of the Pan American Health Organization (PAHO) in 1996 as a basis for national programme development in diabetes. The short-term targets were the designation of national focal points, the preparation of national estimates of the disease burden, and the development and implementation of national strategies and plans to deal with diabetes. The survey found that most countries recognized diabetes as a significant public health problem. In terms of global relevance, a number of lessons have been learned from this exercise: the role of broadly based participation in gaining recognition at the national health policy level; the wide acceptance of an integrated programme model; the relevance of process-related targets to achieve short-term success; and the critical role of having a designated focal point within the managerial approach.

Americas↗

The corn inhibitor of activated Hageman factor: purification and properties of two recombinant forms of the protein.

A cDNA clone that encodes the 14-kDa bifunctional inhibitor from corn seeds (L. Wen et al., Plant Mol. Biol. 18, 813-814, 1992) has been expressed in Escherichia coli after being incorporated into the pT7 expression vector. This inhibitor protein, referred to as CHFI (for the corn inhibitor of activated Hageman factor) or as the popcorn inhibitor, is an important tool for specific inhibition of human activated Hageman factor (activated forms of coagulation Factor XII) and has been well characterized as isolated from corn seeds. Recombinant CHFI was expressed in E. coli in high levels but was insoluble. We solubilized the expressed protein by sonication in 5 M urea and 1% Triton X-100. Several steps of purification, culminating with reversed-phase HPLC, yielded pure, recombinant corn inhibitor in about 5% yield (about 1 mg per liter of culture). The form with which we have worked most, 7N-CHFI, contains 7 amino acid residues at its N-terminus that are encoded by the expression vector. Physical properties of this recombinant protein indicate it has the expected mass and is properly folded. Functionally, 7N-CHFI is indistinguishable from the inhibitor isolated from corn seeds in its inhibition of porcine trypsin, human beta-Factor XIIa, failure to inhibit human plasma kallikrein, and its inhibition of an insect alpha-amylase. A second recombinant form, (4N-11)-CHFI, which lacks 11 residues from the corn inhibitor's N-terminus, is indistinguishable from 7N-CHFI in its pattern of inhibition of the three test proteinases but is inactive against the insect alpha-amylase. This suggests that the N-terminal region of 7N-CHFI forms at least part of the protein's site of interaction with alpha-amylase.

Base Sequence↗

The intrapulmonary percussive ventilator and flutter device compared to standard chest physiotherapy in patients with cystic fibrosis.

Stasis of viscid secretions in cystic fibrosis (CF) leads to chronic infection, inflammation, and lung destruction. Chest physiotherapy (CPT) has been used for many years to assist in the removal of these secretions. However, the need for independently administered CPT exists, particularly for adolescents and the older CF patient. Two devices, the intrapulmonary percussive ventilator (IPV) and the Flutter device (Flutter) have been promoted for this purpose. This study compares these devices to standard, manual CPT. There was no difference in sputum quantity produced with any method studied. Transiently lower oxygen saturation was noted with standard CPT compared with the IPV and Flutter. Inconsistent but significant improvements in flow rates were noted with the two devices compared to standard CPT. Important trends to lower lung volumes, probably indicating decreased air trapping, were also noted with all three therapies at 1 and 4 hours after administration. There were no adverse effects with any treatment regimen. Larger and longer studies of these devices compared to standard CPT and with each other are warranted to assess their value for independent administration of CPT in CF patients and to determine long-term effects on maintenance of pulmonary function.

Adolescent↗

CP-101,606, a potent neuroprotectant selective for forebrain neurons.

The neuroprotective activity of (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol (CP-101,606), an N-methyl-D-aspartate (NMDA) receptor antagonist structurally similar to ((+/-)-(R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-++ +piperidineethanol (ifenprodil), was investigated in neurons in primary culture. CP-101,606 potently and efficaciously protected hippocampal neurons from glutamate toxicity but was > 900-fold less effective for cerebellar granule neurons. The neuroprotective activity in the hippocampal neurons is mediated through a high affinity binding site distinct from the agonist and thienylcyclohexylpiperidine (TCP) binding sites of the NMDA receptor. Autoradiography indicates the CP-101,606 binding site is localized in forebrain, most notably in hippocampus and the outer layers of cortex. The functional selectivity for hippocampal neurons, forebrain localization of binding sites, and structural relation to ifenprodil suggest that CP-101,606 is an NMDA antagonist highly selective for NR2B subunit containing receptors.

Animals↗

Effect of CP101,606, a novel NR2B subunit antagonist of the N-methyl-D-aspartate receptor, on the volume of ischemic brain damage off cytotoxic brain edema after middle cerebral artery occlusion in the feline brain.

BACKGROUND AND PURPOSE: The purpose of this study was to test the hypothesis that the neuroprotective compound CP101,606 will ameliorate the increase in lactate, retard the development of cytotoxic edema, and decrease the infarct volume after ischemic stroke. METHODS: Seventeen adult cats were allocated to control (n = 7) and CP101,606-treated groups (n = 10). Transorbital middle cerebral artery occlusion was performed under anesthesia. Extracellular fluid lactate by microdialysis as well as infarct volume measurement by triphenyltetrazolium chloride (TTC)-stained section, with and without neuroprotective agents, was used to determine the value of these potential "surrogate markers" of ischemic damage. RESULTS: The control group showed an increased dialysate lactate (15.5% increase) at 30 minutes and a peak (332.0% increase) in dialysate lactate at 1 hour after middle cerebral artery occlusion compared with the drug-treated group. Significant differences between control and drug-treated groups were seen in the rate of fall of the apparent diffusion coefficient at both 1 and 5 hours. A close correlation was seen between the 1- and 5-hour apparent diffusion coefficient maps and the TTC-stained sections. There was a significantly smaller lesion in the CP101,606-treated group (62.9% reduction in infarct size compared with the control group; P < .001). CONCLUSIONS: CP101,606 ranks very highly among the current neuroprotection candidates for clinical trials, and its excellent safety record in both animals and phase II studies in conscious, moderate head injury patients suggests that it will be highly effective in human occlusive stroke.

Animals↗

Capture-recapture: reconnaissance of a demographic technique in epidemiology.

The objective of this paper is to review capture-recapture (CR) methodology and its usefulness in epidemiology. Capture-recapture is an established and well-accepted sampling tool in wildlife studies, and it has been proposed as a cost-effective demographic technique for conducting censuses. However, the application of CR in the field of epidemiology requires consideration of relevant factors such as the nature of the condition under surveillance, its case definition, patient characteristics, reporting source and propensity for misdiagnosis and underdiagnosis. The use of CR in epidemiology has expanded over the last 10 years and no doubt will continue to be adopted. Although it has a role in public health surveillance, a more traditional approach to disease monitoring seems more advantageous in certain instances.

Canada↗

Interlaboratory comparison of sequence-specific PCR and ligase detection reaction to detect a human immunodeficiency virus type 1 drug resistance mutation. The AIDS Clinical Trials Group Virology Committee Drug Resistance Working Group.

Sequence-specific PCR was used in six laboratories and a ligase detection reaction was used in one laboratory to detect the zidovudine-resistance mutation at codon 215 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase DNA. The genotypes of 27 different clinical samples, including cultured HIV-1 isolates, peripheral blood mononuclear cells, and plasma, were correctly identified by 140 of 154 (91%) assays. The sensitivity for detecting a mutation was 96% for HIV-1 reverse transcriptase DNA clone mixtures containing 30% mutant DNA and 62% for mixtures containing 6% mutant DNA.

Antiviral Agents↗

Trends in cervical cancer mortality in the Americas.

This article presents an assessment of cervical cancer mortality trends in the Americas based on PAHO data. Trends were estimated for countries where data were available for at least 10 consecutive years, the number of cervical cancer deaths was considerable, and at least 75% of the deaths from all causes were registered. In contrast to Canada and the United States, whose general populations had been screened for many years and where cervical cancer mortality has declined steadily (to about 1.4 and 1.7 deaths per 100,000 women, respectively, as of 1990), most Latin American and Caribbean countries with available data have experienced fairly constant levels of cervical cancer mortality (typically in the range of 5-6 deaths per 100,000 women). In addition, several other countries (Chile, Costa Rica, and Mexico) have exhibited higher cervical cancer mortality as well as a number of noteworthy changes in this mortality over time. Overall, while actual declining trends could be masked by special circumstances in some countries, cervical cancer mortality has not declined in Latin America as it has in developed countries. Correlations between declining mortality and the intensity of screening in developed countries suggest that a lack of screening or screening program shortcomings in Latin America could account for this. Among other things, where large-scale cervical cancer screening efforts have been instituted in Latin America and Caribbean, these efforts have generally been linked to family planning and prenatal care programs serving women who are typically under 30; while the real need is for screening of older women who are at substantially higher risk.

Adult↗

Effect of human T-lymphotropic virus type I infection on non-Hodgkin's lymphoma incidence.

BACKGROUND: We previously reported from a case-control analysis that T-cell non-Hodgkin's lymphoma (NHL) was strongly associated with human T-lymphotropic virus type I (HTLV-I) infection in Jamaica and Trinidad and that the relative risk for HTLV-I infection was very high in younger patients. PURPOSE: The objective of this study was to estimate the age-specific incidence rates of NHL among HTLV-I-infected and HTLV-I-uninfected adults in Jamaica and Trinidad. METHODS: Population rates of HTLV-I infection were calculated from available census reports and serosurvey data. Incidence rates for NHL were calculated from all incident cases in Jamaica during 1984-1987 (n = 135) and from all incident cases in Trinidad during 1986-1990 (n = 117). Using biopsy material, we determined whether the immunophenotype of the tumor cells was T cell, B cell, or other. NHL incidence rates were computed according to HTLV-I status, age, sex, and tumor phenotype for each country separately and for both countries combined by weighting to the relative population size of each country. RESULTS: The age-standardized NHL incidence rate (mean +/- SE) in Jamaica was 1.9 +/- 0.2 per 100,000 person-years (PY). In Trinidad, the rate was 2.9 +/- 0.4 per 100,000 PY. Overall, the incidence of NHL increased with age and was higher in males than in females. In the HTLV-I-infected population, the incidence of NHL was inversely related to age, and age-specific rates were higher in males than in females. The NHL incidence in those estimated to have acquired HTLV-I infection in childhood, however, showed no sex difference, and one in 1300 such carriers (95% confidence interval: one in 1100 to one in 1600) per annum were estimated to be at such risk. For T-cell NHL, as proxy for adult T-cell lymphoma/leukemia, incidence was highest in those patients infected with HTLV-I early in life (perinatally or via breast milk), with high, sustained risk from early adulthood in both sexes. CONCLUSIONS: While overall NHL incidence rates reveal that HTLV-I endemicity does not impose an exaggerated lymphoma burden on these populations, the risk for lymphoma among carriers who acquire infection early in life is dramatic and is consistent with the hypothesis that virus exposure early in life is most important for lymphoma-genesis. IMPLICATIONS: Studies of HTLV-I carriers known to be infected in childhood may provide insight into markers intermediate in the lympho-magnetic process. Strategies to disrupt early-life transmission of HTLV-I, notably mother-infant transmission, may be critical in reducing the burden of lymphoreticular disease in these populations.

Adolescent↗

Comparison of effects of an intrapulmonary percussive ventilator to standard aerosol and chest physiotherapy in treatment of cystic fibrosis.

Impaired mucociliary clearance due to defective ion and water transport and the effects of chronic airway infections lead to stasis of secretions and progressive pulmonary damage in patients with cystic fibrosis (CF). Methods to improve removal of tenacious lung secretions in CF patients contribute to slowing the decline in respiratory function. We have evaluated an intrapulmonary percussive ventilator (IPV), which is a device designed to enhance airway clearance and preserve lung function. A previous pilot study by us had determined that the device was acceptable to patients and is safe. We undertook a 6 month parallel comparative trial of the IPV versus standard, manual chest physiotherapy in 16 CF children and adults. No significant differences in spirometric measures, numbers of hospitalizations, use of oral or IV antibiotics, or anthropometric measurements were detected between the standard aerosol/chest physiotherapy group and the IPV group over the duration of the trial. Patient acceptance, as determined by participant survey, was good. The device appeared to be safe and durable. It was concluded that the IPV is as effective as standard aerosol and chest physiotherapy in preserving lung function and anthropometric measures, and there was no difference in the use of antibiotics and hospitalizations.

Adolescent↗

Magnetic resonance imaging in phenylketonuria: reversal of cerebral white matter change.

OBJECTIVES: To investigate the extent to which the abnormalities in cerebral white matter in adolescents and adults with phenylketonuria (PKU) are reversible. METHOD: Magnetic resonance imaging (MRI) of the brain was repeated in 41 patients with PKU (age range, 14 to 49 years) after an interval (median, 9 months; range, 3 to 12 months) of dietary intervention. Scans were scored according to the extent of the white matter involvement. After an initial MRI, five patients returned to a strict low-phenylalanine diet with amino acid supplement; 21 patients started a low-protein diet (1 gm/kg) with amino acids supplement; and 15 patients made no dietary alteration. RESULTS: Scans improved in all five patients who returned to a strict low-phenylalanine diet, in 5 of the 21 patients on the low-protein diet plus amino acid supplement, and in 4 of the 15 patients who made no dietary change. There was a significant association between change in the MRI findings and in the blood phenylalanine concentration (Pearson correlation: r = 0.55; p < 0.0002) and between change in the MRI and in the phenylalanine level at the time of the second scan (r = 0.58; p < 0.0001). Improvement was seen primarily in those in whom phenylalanine levels were reduced to less than 900 mumol/L. There was no obvious change in MRI score after 3 weeks of strict phenylalanine restriction for the two adults who underwent serial scanning. CONCLUSION: The MRI changes in PKU are at least partially reversible by lowering the blood phenylalanine concentration.

Adolescent↗

Diagnosis of symptomatic visceral leishmaniasis by use of the polymerase chain reaction on patient blood.

To diagnose symptomatic visceral leishmaniasis (kala-azar) using peripheral blood rather than tissue aspirates, a polymerase chain reaction (PCR) technique was developed for which the detection limit is 1 Leishmania-infected macrophage in 8 mL of blood. For Indian, Kenyan, or Brazilian patients with parasitologically confirmed kala-azar, 57 of 63 cases before treatment had blood that was PCR-positive (90% sensitivity). None of 40 clinically healthy persons had PCR-positive blood (100% specificity). Twelve (92%) of 13 clinically cured Indian patients had negative PCR reactions 1-6 months after treatment. This PCR procedure can provide a parasitologic diagnosis for the vast majority of kala-azar cases before therapy, may identify patients who have been successfully treated by chemotherapy, and should substantially reduce the need for invasive tests.

Base Sequence↗

HIV-1 prevalence and risk factors among sexually transmitted disease clinic attenders in Trinidad.

OBJECTIVES: To study trends in prevalence and to ascertain risk factors for HIV-1 among sexually transmitted disease (STD) clinic attenders in Trinidad. DESIGN AND METHODS: Serial cross-sectional studies were conducted in 1987-1988 and 1990-1991 at a centralized STD clinic in Port of Spain. A case-control study was carried out to examine in greater detail the demographic and behavioral risk factors for HIV-1 among self-declared heterosexuals in this population. RESULTS: HIV-1 prevalence increased from 3.0% [95% confidence interval (CI), 2.3-3.9] in 1987-1988 to 13.6% (95% CI, 11.8-15.6) in 1990-1991. Age > or = 40 years [odds ratio (OR), 2.0; 95% CI, 1.4-2.8], urban residence (OR, 2.2; 95% CI, 1.6-3.0), and human T-lymphotropic virus-I seropositivity (OR, 3.1; 95% CI, 1.6-6.0) were significant risk factors for HIV-1 in 1990-1991. In the case-control analysis, significant independent risk factors for men included current genital ulcer disease (OR, 5.2; 95% CI, 2.2-12.5), current genital warts (OR, 3.9; 95% CI, 1.2-12.0), having ever had syphilis (OR, 3.2; 95% CI 1.6-6.1), and use of crack cocaine in the preceding 6 months (OR, 6.2; 95% CI, 2.7-14.2). Corresponding risk factors for women were commercial sex work (OR, 5.7; 95% CI, 1.3-25.7), initiation of sexual activity before age 14 years (OR, 4.8; 95% CI, 1.5-16.0), and past non-gonococcal cervicitis (OR, 4.1; 95% CI, 1.3-13.1). CONCLUSIONS: HIV-1 in this setting is primarily heterosexually transmitted in a milieu of unprotected sexual activity fuelled by a crack cocaine epidemic. Targeted interventions to prevent, detect and treat STD and crack cocaine addiction, as well as disrupt their adverse synergism, may substantially reduce HIV-1 transmission in this population.

Adult↗

CHLORIDE-DEPENDENT ORGANIC PHOSPHATE SENSITIVITY OF THE OXYGENATION REACTION IN CROCODILIAN HEMOGLOBINS

We show that crocodilian hemoglobins (Hbs), which previously have been considered to be model pigments lacking allosteric interaction with organic phosphate esters, do exhibit oxylabile ATP and 2,3-diphosphoglycerate (DPG) binding that decreases O2 affinity and increases pH sensitivity (Bohr effect), in the absence of Cl- and at the low Cl- concentrations that may occur in crocodilian plasma during 'post-ingestive alkaline tides'. Hbs from different species vary in their phosphate sensitivities. In Alligator mississippiensis Hb, O2 affinity shows greater ATP than DPG sensitivity at low [cofactor]/[Hb] ratios. In Paleosuchus palpebrosus Hb, where even a high Cl- concentration (0.1 mol l-1) does not completely suppress the phosphate effects, the opposite is true, whereas both ATP and DPG exert similar effects in Caiman crocodilus Hb. Lactate, at concentrations that may occur after intensive exercise, similarly depresses Hb O2-affinity, indicating an O2 demand/O2 supply feedback regulation. Curiously, inositol hexaphosphate (IHP), a potent allosteric effector in other vertebrate Hbs, has no effect on A. mississippiensis and P. palpebrosus Hb and only small effects on C. crocodilus Hb, presumably because of steric hindrance at the binding site. The molecular mechanisms underlying the observations (particularly the implication of ss82-Lys, i.e. the lysine residue at position 82 of the ss-chains that binds phosphate and Cl-) are considered. Their physiological significance requires further study.

Journal Article↗