Observation of D0-->K+ pi -
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Journal Article↗
Biomedical subjects
R Wilson
Publications and source records attributed to R Wilson.
2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans.
As part of our effort to sequence the 100-megabase (Mb) genome of the nematode Caenorhabditis elegans, we have completed the nucleotide sequence of a contiguous 2,181,032 base pairs in the central gene cluster of chromosome III. Analysis of the finished sequence has indicated an average density of about one gene per five kilobases; comparison with the public sequence databases reveals similarities to previously known genes for about one gene in three. In addition, the genomic sequence contains several intriguing features, including putative gene duplications and a variety of other repeats with potential evolutionary implications.
Animals↗
Asbestos in New York City public school buildings--public policy: is there a scientific basis?
The most recent of New York City's asbestos emergencies occurred in the late summer of 1993. It prevented schools from opening that fall, precipitated much media excitement, and caused a flurry of widespread abatement activities. This resulted in large measure from the U.S. Environmental Protection Agency's subjective school building inspection policy concerning identification of asbestos hazards in buildings and the subsequent Asbestos Hazard Emergency Response Act mandate for inspection. Data on concentrations of asbestos in the air, important for the calculation of risk to building occupants, were not required and therefore not obtained, as part of the abatement strategy or priority setting. Based on fiber-in-air measurements obtained elsewhere, the calculated risk to NYC school children, using the most pessimistic models, was less than six excess cancer deaths per million lifetimes equivalent to smoking less than a dozen cigarettes in a lifetime. The NYC administration responded to pressure from parent groups concerned with perceived asbestos risks to their children by closing the schools. The hysteria occurred because much of EPA's policy lacked a scientific basis for risk evaluation and assessment.
Air Pollution, Indoor↗
Immunological changes in pregnancy-induced hypertension.
Aspects of T and B cell function were studied in women with pregnancy-induced hypertension (PIH) and normotensive pregnant women by determining the proliferation of peripheral blood mononuclear cells (PBMC) with or without stimulation by mitogens (PHA, ConA and PWM) and by determining IgG and IgM levels in the culture supernatant. The results showed that the proliferation of PBMC without mitogens was significantly increased in PIH women without proteinuria compared with normotensive pregnant women. In the presence of PHA, [3H]thymidine uptake in PBMC was statistically higher in PIH women both with and without proteinuria than that in normotensive pregnant women. ConA and PWM mitogen activities were not significantly different between PIH women and normotensive pregnant women. Compared with normotensive pregnant women, IgG production was significantly increased in PIH women with proteinuria but not in those without proteinuria. IgM production was not changed in PIH women. We concluded that immunologic responses in PIH women were increased rather than decreased. This increased immunologic activity is in accordance with some important changes seen in PIH, such as an increase in intracellular calcium, the presence of blood-borne mitogenic factor and a decrease in prostaglandin E series. These findings also support the hypothesis that PIH might result from the imbalance between fetal antigenic load and maternal production of immunologic blockade.
Adult↗
Nervonic acid and demyelinating disease.
Demyelination in adrenoleukodystrophy (ALD) is associated with an accumulation of very long chain saturated fatty acids such as 26:0 stemming from a genetic defect in the peroxisomal beta oxidation system responsible for the chain shortening of these fatty acids. Long chain monoenoic acids such as erucic acid, 22:1(n-9), can normalise elevated serum levels of 26:0 in ALD by depressing their biosynthesis from shorter chain saturated fatty acids. Sphingolipids from post mortem ALD brain have decreased levels of nervonic acid, 24:1(n-9), and increased levels of stearic acid, 18:0. Increased levels of 26:0 are accompanied by decreased nervonic acid biosynthesis in skin fibroblasts from ALD patients. Sphingolipids from post mortem MS brain have the same decreased 24:1(n-9) and increased 18:0 seen in post mortem ALD brain. The 24:1(n-9) content of sphingomyelin is depressed in erythrocytes from multiple sclerosis (MS) patients. Defects in the microsomal biosynthesis of very long chain fatty acids including 24:1(n-9) in 'jumpy' and 'quaking' mice are accompanied by impaired myelination. An impairment in the provision of nervonic acid in demyelinating diseases is indicated, suggesting that dietary therapy with oils rich in very long chain monenoic acid fatty acids may be beneficial in such conditions.
Adrenoleukodystrophy↗
Oxidant-mediated ciliary dysfunction in human respiratory epithelium.
Exposure of human nasal ciliated epithelium to reactive oxidants generated by the enzymatic xanthine-xanthine oxidase superoxide/hydrogen peroxide (H2O2) and glucose-glucose oxidase H2O2-generating systems, or to reagent H2O2 or hypochlorous acid (HOCl) resulted in significant alterations in ciliary beating. The earliest change noted was the presence of ciliary slowing, progressing eventually to complete ciliary stasis in some areas. Ciliary dyskinesia was seen within the first hour, often from as early as 15 min after exposure of the cells to reactive oxidants. Using peroxidases, various antioxidant enzymes, and oxidant scavengers, we confirmed that these detrimental effects on ciliary function were mediated primarily by H2O2 and HOCl. Moreover, 3-aminobenzamide (3-ABA), an inhibitor of the DNA repair enzyme poly ADP ribose polymerase, prevented H2O2-mediated inhibition of ciliary function, indicating that oxidant-mediated damage to DNA may well be the basis of the effects of H2O2 on ciliated epithelium. Acute and chronic inflammatory responses may therefore present the possible threat of H2O2- or HOCl-inflicted injury on bystander respiratory epithelium, leading to ciliary dyskinesia and slowing.
Catalase↗
Prospective risk stratification in renal transplant candidates for cardiac death.
In previous studies to predict future cardiac death of patients undergoing evaluation for renal transplantation, noninvasive or invasive testing of all, or nearly all, patients has been used. In an attempt to decrease the cost of cardiac risk assessment, we prospectively used a two-tiered cardiac risk assessment algorithm on 189 consecutive patients referred for renal transplant evaluation. First, patients were stratified by clinical characteristics of age > or = 50 years, history of angina, insulin-dependent diabetes, congestive heart failure, or abnormal electrocardiogram (excluding left ventricular hypertrophy). Patients having none of these risk factors (n = 94) were considered at low risk for cardiac events and underwent no further cardiac evaluation. Patients with one or more of the cardiac risk factors (n = 95) were considered to be in a high-risk group and were required to undergo further evaluation with thallium myocardial scintigraphy. Follow-up of patients was for 46 +/- 16 months. Cardiac mortality was significantly higher in the clinical high-risk group compared with the clinical low-risk group (17% v 1%, respectively; P < 0.001). Further cardiac risk stratification was evident by thallium myocardial scintigraphy. Patients with reversible thallium defects had significantly higher cardiac mortality rates than patients with no thallium defects (23% v 5%, respectively; P < 0.05). Fixed thallium defects also had predictive value for cardiac mortality (29%,; P < 0.05), but deaths in this fixed defect group tended to occur later in the follow-up period. The initial clinical stratification obviated the need for further noninvasive or invasive testing in nearly half of the renal transplant candidates.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Spatial displacement limits for cyclopean (stereoscopic) apparent-motion perception.
The range of spatial displacements over which cyclopean (stereoscopic) apparent motion is perceived was investigated. The cyclopean stimuli were created from retinal disparity embedded in dynamic random-dot stereograms. In one experiment, the displacement range for crossed-disparity cyclopean motion was compared with that for luminance-domain motion. The results showed that cyclopean motion was perceived over spatial displacements that were about two to three times larger than the displacements over which luminance motion was perceived. In a second experiment, the displacement range for crossed-disparity cyclopean motion was compared with that for uncrossed-disparity cyclopean motion. The results revealed that the displacement range was restricted (motion quality was poor) for uncrossed motion relative to crossed motion. It is inferred that cyclopean motion from crossed disparity is represented at a coarse spatial scale, relative to luminance motion, and that cyclopean motion from uncrossed disparity is suppressed due to occlusion cues present when uncrossed stimuli are seen behind a textured background.
Female↗
The concentrations of clarithromycin and its 14-hydroxy metabolite in sputum of patients with bronchiectasis following single dose oral administration.
Clarithromycin and its metabolite, 14-hydroxy-clarithromycin are active against a wide range of respiratory pathogens. Antibiotics generally penetrate poorly into respiratory secretions which may therefore continue to harbour bacteria following bronchial infection. We have studied sputum and serum concentrations of clarithromycin and 14-hydroxy-clarithromycin in eight patients with idiopathic bronchiectasis without infective exacerbations (five male, three female; mean age 53.3 years). Oral single dose administration of 250 or 500 mg clarithromycin, separated by at least 6 days, was given to each patient. Serum and sputum samples were collected (the latter by physiotherapy at 0, 1, 2, 4, 8, 24 and 0, 4, 8 and 24 h respectively after administration of each dose. Serum sol phase was obtained by high speed centrifugation and concentrations of clarithromycin and 14-hydroxy-clarithromycin were determined by high performance liquid chromatography. Serum Cmax for clarithromycin and 14-hydroxy-clarithromycin were 1.20 mg/L (3 h) and 0.37 mg/L (3.1 h) for clarithromycin (250 mg)) and were 2.78 mg/L (2.5 h) and 0.68 mg/L (2.6 h) for clarithromycin (500 mg) respectively. Sputum Cmax for clarithromycin and 14-hydroxy-clarithromycin were 0.52 mg/L (5 h) and 0.30 mg/L (5.5 h) for clarithromycin (250 mg) and were 1.59 mg/L (5 h) and 0.47 mg/L (5.5 h) for clarithromycin (500 mg) respectively. The sputum/serum percentage ratios at Cmax (sputum) for clarithromycin and 14-hydroxy-clarithromycin were 74.3% and 113.9% (250 mg) and 94.7% and 99.9% (500 mg) respectively. We conclude that oral administration of clarithromycin to patients with bronchiectasis results in rapid penetration into respiratory mucus with persistent drug concentrations that exceed its MIC for many respiratory pathogens.
Administration, Oral↗
Animal models of respiratory infection.
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Animals↗
The effect of erythromycin on Pseudomonas aeruginosa and neutrophil mediated epithelial damage.
Erythromycin therapy for long periods may benefit patients with chronic bronchial sepsis colonized by Pseudomonas aeruginosa despite the lack of antibacterial activity. We have investigated the effect of filtrates of 24 h P. aeruginosa cultures (CF) with or without erythromycin 0.5, 5, 20 mg/L on human nasal epithelium in the absence or presence of polymorphonuclear leucocytes (PMN). Ciliary beat frequency (CBF) and epithelium integrity were examined for 4 h. Erythromycin (20 mg/L) alone did not affect epithelium. CF without erythromycin slowed CBF by 63.5% of control at 4 h, and caused disruption of surface integrity in 80% of the epithelium. Addition of erythromycin to CF did not inhibit these effects. Erythromycin did not affect growth of P. aeruginosa. Filtrates of P. aeruginosa cultured with erythromycin (5 and 20 mg/L) caused less CBF slowing (37.2% and 19.2% of control, respectively) and epithelial disruption (4.2% and 6.7%, respectively). Unstimulated PMN (10(7)/mL) slowed CBF by 13% of control at 4 h but did not cause epithelial disruption. PMN and CF together slowed CBF (95.4% of control) and damaged epithelium (93.3% of epithelium disrupted) synergically. Pre-incubation of PMN with erythromycin did not inhibit these effects. PMN and filtrates of P. aeruginosa cultured with erythromycin (5 and 20 mg/L) caused less CBF slowing (58.0% and 33.6% of control, respectively) and epithelial disruption (40.0% and 13.3%, respectively). Erythromycin may benefit patients by reducing P. aeruginosa production of factors which damage epithelium and stimulate neutrophil mediated cytotoxicity.
Bacterial Toxins↗
Efficacy and safety of long-term ciprofloxacin in the management of severe bronchiectasis.
The efficacy and safety of long-term ciprofloxacin therapy in the management of severe bronchiectasis were retrospectively assessed in patients who had taken oral ciprofloxacin continuously for at least 90 days. The drug was well tolerated, with only one reported side effect. Treatment resulted in a symptomatic improvement in seven of the ten patients and significant improvements in peak expiratory flow rate and residual volume. There was a decrease in the number of infective exacerbations from 6.2 +/- 2.9 during 365 days to 0.5 +/- 0.53 during 412 days. Resistance to ciprofloxacin developed in 2 patients with Pseudomonas aeruginosa infection and this was associated with clinical deterioration, but in a further two patients with P. aeruginosa the pathogen was eradicated. Two patients had persistent Streptococcus pneumoniae cultured from sputum but this was not associated with clinical deterioration. The study suggests that ciprofloxacin is effective and safe in the long-term treatment of chronic bronchial sepsis due to bronchiectasis, but emergence of P. aeruginosa resistance is of some concern.
Adult↗
Developing an ethics curriculum for a family practice residency.
PURPOSE: To develop a curriculum in ethics in family practice by studying which ethical issues physicians believe to be important based on frequency of encounter, difficulty in managing the problem, and helpfulness of discussion; to examine whether there are any important differences between faculty and residents and between genders; and to determine the preferred format(s) for teaching these issues. METHOD: Between November 1991 and June 1992 a total of 475 questionnaires were mailed to all the family practice residents (first- and second-year), graduates in their first two years of practice, and the physician faculty of the Department of Family Medicine at the McGill University Faculty of Medicine. Overall, 319 usable questionnaires were returned, for a final response rate of 67%. The questionnaire asked respondents to evaluate 14 ethical dilemmas in order to determine the importance of teaching specific ethical issues as well as to determine the preferred format for teaching. Chi-square tests, analyses of variance, and Student's t-tests were used to test the significance of differences in responses. RESULTS: No consistent pattern of interrelationship was found among frequency of encounter and difficulty and helpfulness of discussion for most items. Overall, there was little difference in how faculty and residents, men and women, perceived the importance of these ethical issues. Women reported encountering ethical issues less frequently than men [F (14,285) = 1.82, p < .04], while at the same time finding them somewhat more difficult and more deserving of discussion. Small-group, case-oriented discussion appears to have been the favored teaching format regardless of the ethical dilemma. CONCLUSION: It is difficult to narrow down the content to be included in a curriculum in ethics in family practice. Frequency of encounter, difficulty in management, and helpfulness of discussion can all be argued to be important factors for consideration; they should all be considered separately or in combination for each teaching situation if time restrictions force a choice between topics.
Adult↗
Comparison of iopromide with iohexol and iopamidol in coronary arteriography and left ventriculography.
RATIONALE AND OBJECTIVES: Low-osmolality contrast agents, ionic and nonionic, are being used more frequently in coronary arteriography. A new nonionic contrast agent, iopromide, has recently become available for use in clinical trials. The purpose of this phase II-phase III Food and Drug Administration (FDA) trial was to compare the side effects and diagnostic quality of iopromide with iohexol and iopamidol for coronary arteriography and left ventriculography. METHODS: Two separate double-blind trials were performed using iopromide and comparison nonionic contrast agents. In the first trial, 41 patients were randomized to receive iopromide or iopamidol. The second trial was a three-center trial involving 120 patients, of whom half received iopromide (370 mg I/mL) and the other half received iohexol (350 mg I/mL). In a third study, 26 patients received iopromide (370 mg I/mL) according to an open-label design. RESULTS: Comparison of iopromide with the other agents revealed that there were no significant differences in adverse events between iopromide and the comparison agents. Most adverse reactions were mild or moderate in severity in all patient groups. There was no difference in the patients' perceptions of heat and pain and no statistically significant difference in systolic or diastolic blood pressure at baseline, at 30 to 60 minutes, or at 24 hours after the procedure. No difference was found in the biochemical or hematologic analysis at baseline or at 24-hour follow-up. No difference between the contrast media groups in terms of the quality of the left ventriculogram or the quality of the coronary arteriography was noted. CONCLUSION: Compared to the other nonionic agents, iopromide showed no statistically significant differences in terms of safety or efficacy.
Contrast Media↗
Effect of salmeterol on human nasal epithelial cell ciliary beating: inhibition of the ciliotoxin, pyocyanin.
1. Patients with airway infection by Pseudomonas aeruginosa have impaired mucociliary clearance. Pyocyanin is a phenazine pigment produced by P. aeruginosa which is present in the sputum of colonized patients, slows human ciliary beat frequency (CBF) in vitro and slows mucociliary transport in vivo in the guinea-pig. 2. We have investigated the effect of salmeterol, a long-acting beta 2-adrenoceptor agonist, on pyocyanin-induced slowing of human CBF in vitro. Salmeterol (2 x 10(-7) M) was found to reduce pyocycanin (20 micrograms ml-1)-induced slowing of CBF by 53% and the fall in intracellular adenosine 3':5'-cyclic monophosphate (cyclic AMP) by 26% and ATP by 29%. 3. Another beta 2-adrenoceptor agonist, isoprenaline (2 x 10(-7) M), also inhibited pyocyanin-induced slowing of CBF by 39%. 4. The effects of salmeterol (30 min preincubation) persisted after washing the cells. 5. Propranolol (10(-7) M) and the beta 2-specific antagonist, ICI 118551 (10(-6) M) blocked the protective effects of salmeterol completely, but atenolol (10(-6) M) was less effective. These results suggested that the effects of salmeterol on pyocyanin-induced effects were mediated primarily via the stimulation of beta 2-adrenoceptors. 6. Pyocyanin-induced ciliary slowing is associated with a substantial fall in intracellular cyclic AMP and ATP. Salmeterol reversed the effects of pyocyanin on cyclic AMP and ATP. 7. Mucociliary clearance is an important defence mechanism of the airways against bacterial infection. Salmeterol may benefit patients colonized by P. aeruginosa, not only by its bronchodilator action, but also by protecting epithelial cells from pyocyanin-induced slowing of CBF.
Adenosine Triphosphate↗
Effect of tracheal cytotoxin from Bordetella pertussis on human neutrophil function in vitro.
The infiltration of neutrophils which phagocytose and kill microorganisms is an important defense mechanism against infections of the airways. Bordetella pertussis is a human respiratory pathogen which colonizes ciliated epithelium, causing whooping cough. We have investigated the effects of the peptidoglycan fragment tracheal cytotoxin (TCT) of B. pertussis on human neutrophil function in vitro. TCT (10(-6) to 10(-8) M) was toxic for human neutrophils, as measured by lactate dehydrogenase release and levels of intracellular ATP. TCT (10(-9) to 10(-15) M) did not stimulate neutrophil migration or chemiluminescence and did not affect neutrophil phagocytosis. Incubation of neutrophils for 20 min with TCT (10(-9) to 10(-11) M) significantly inhibited (P < 0.05) their subsequent migration toward the chemotactic factor N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 10(-9) M). Incubation of neutrophils for 20 min with TCT (10(-9) to 10(-15) M) significantly inhibited (P < 0.05) chemiluminescence stimulated by FMLP (10(-5) M). TCT (10(-6) to 10(-12) M) did not stimulate interleukin-1 alpha production by neutrophils or serum complement activation by the alternate pathway. We conclude that TCT at concentrations of < 10(-8) M affects important neutrophil functions and at higher concentrations is toxic. TCT may therefore contribute to the survival of B. pertussis within the airways in vivo.
Bordetella pertussis↗
Measurement issues in research on social support and health.
STUDY OBJECTIVE: The aims were: (1) to identify methodological problems that may explain the inconsistencies and contradictions in the research evidence on social support and health, and (2) to validate a frequently used measure of social support in order to determine whether or not it could be used in multivariate analyses of population data in research on social support and health. DESIGN AND METHODS: Secondary analysis of data collected in a cross sectional survey of a multistage cluster sample of the population of the United States, designed to study relationships in behavioural, social support and health variables. Statistical models based on item response theory and graph theory were used to validate the measure of social support to be used in subsequent analyses. PARTICIPANTS: Data on 1755 men and women aged 20 to 64 years were available for the scale validation. RESULTS: Massive evidence of item bias was found for all items of a group membership subscale. The most serious problems were found in relationship to an item measuring membership in work related groups. Using that item in the social network scale in multivariate analyses would distort findings on the statistical effects of education, employment status, and household income. Evidence of item bias was also found for a sociability subscale. When marital status was included to create what is called an intimate contacts subscale, the confounding grew worse. CONCLUSIONS: The composite measure of social network is not valid and would seriously distort the findings of analyses attempting to study relationships between the index and other variables. The findings show that valid measurement is a methodological issue that must be addressed in scientific research on population health.
Adult↗
X-linked adrenoleukodystrophy with non-diagnostic plasma very long chain fatty acids.
Measurement of plasma very long chain fatty acids is widely recognised as a sensitive screening test for X-linked adrenoleukodystrophy (X-ALD). This test has particular importance because of the highly variable clinical expression of X-ALD. In this affected family the progressive childhood form of X-ALD was accompanied by "non-diagnostic" concentrations of plasma very long chain fatty acids. The implications for diagnosis of X-ALD are discussed.
Adrenoleukodystrophy↗