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Biomedical subjects

H Quan

Publications and source records attributed to H Quan.

At least 55 records · Page 3Linked to original sources
PubMed1999

Elderly suicide in Alberta: difference by gender.

OBJECTIVE: To determine differences by gender among elderly persons who commit suicide on demographic characteristics, place of suicide, suicide method, previous suicide behaviour, and precipitant stressor. METHOD: This study included completed suicides of individuals aged 55 years and over during 1984-1995 in Alberta (n = 920). Information was abstracted from suicide records of medical examiners. RESULTS: Relative to elderly female suicides, elderly males who commit suicide characteristically use guns to commit suicide (43.8%), are single (12.5%), live in rural areas (46.7%), and have a lower frequency of previous suicide attempts (16.5%). Physical illness and financial difficulty as precipitant stressors of suicide are significantly more frequent among males (40.3% and 8.7% respectively) than females (29.9% and 1.8% respectively). Mental illness as a precipitant stressor is more common among females, 35.8% for women and 15.3% for men. CONCLUSIONS: Lethal methods of suicide and physical illness and financial difficulty as precipitant stressors of suicide are more common among elderly males than females who commit suicide.

Aged↗
PubMed1999

Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids.

Conventional nonsteroidal anti-inflammatory drugs inhibit both cyclooxygenase (Cox) isoforms (Cox-1 and Cox-2) and may be associated with nephrotoxicity. The present study was undertaken to assess the renal effects of the specific Cox-2 inhibitor, MK-966. Healthy older adults (n = 36) were admitted to a clinical research unit, placed on a fixed sodium intake, and randomized under double-blind conditions to receive the specific Cox-2 inhibitor, MK-966 (50 mg every day), a nonspecific Cox-1/Cox-2 inhibitor, indomethacin (50 mg t.i.d.), or placebo for 2 weeks. All treatments were well tolerated. Both active regimens were associated with a transient but significant decline in urinary sodium excretion during the first 72 h of treatment. Blood pressure and body weight did not change significantly in any group. The glomerular filtration rate (GFR) was decreased by indomethacin but was not changed significantly by MK-966 treatment. Thromboxane biosynthesis by platelets was inhibited by indomethacin only. The urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto prostaglandin F1alpha was decreased by both MK-966 and indomethacin and was unchanged by placebo. Cox-2 may play a role in the systemic biosynthesis of prostacyclin in healthy humans. Selective inhibition of Cox-2 by MK-966 caused a clinically insignificant and transient retention of sodium, but no depression of GFR. Inhibition of both Cox isoforms by indomethacin caused transient sodium retention and a decline in GFR. Our data suggest that acute sodium retention by nonsteroidal anti-inflammatory drugs in healthy elderly subjects is mediated by the inhibition of Cox-2, whereas depression of GFR is due to inhibition of Cox-1.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Coronary artery bypass grafting in Canada: hospital mortality rates, 1992-1995.

BACKGROUND: Rates of in-hospital death after coronary artery bypass grafting (CABG) have been studied in many regions of Canada as possible indicators of hospital-specific quality of care. This nationwide study examined observed and risk-adjusted death rates for 23 Canadian hospitals performing CABG. METHODS: Hospital discharge data were obtained from the Canadian Institute for Health Information and were used to identify all CABG procedures performed in Canadian hospitals in fiscal years 1992/93 through 1995/96. Cases from Quebec hospitals were not studied because hospitals in that province do not report to the institute. Observed death rates were evaluated, and a logistic regression model was used to calculate a risk-adjusted death rate for each hospital for the 4-year period studied. Changes over time in hospital-specific death rates were also examined. RESULTS: A total of 50,357 CABG cases were studied, with an overall death rate of 3.6%. Interhospital comparisons showed that average severity of illness varied considerably across hospitals. Despite risk adjustment accounting for this variable severity, there was considerable variation in adjusted death rates across the 23 hospitals, from 1.95% to 5.76% (p < 0.001 for difference across hospitals). For some hospitals, death rates decreased between 1992/93 and 1995/96, whereas for others the rates were stable or increased. INTERPRETATION: Risk-adjusted rates of in-hospital death after CABG vary widely across Canadian hospitals. There may be differences in quality of care across hospitals, and focused quality-improvement initiatives may be necessary in some institutions.

Adult↗
PubMed1998

Coronary artery bypass grafting in Canada: national and provincial mortality trends, 1992-1995.

BACKGROUND: Despite a body of research on outcomes of coronary artery bypass grafting (CABG) in Canada, little is known about Canada-wide outcome trends and interregional differences in outcome. The objectives of this study were to examine Canadian trends in rates of in-hospital death after CABG and to compare provincial risk-adjusted death rates. METHODS: Hospital discharge data were obtained from the Canadian Institute for Health Information and were used to identify complete cohorts of patients who underwent CABG in 8 provinces in fiscal years 1992/93 through 1995/96. Data from Quebec hospitals were not available. A logistic regression model was used to calculate risk-adjusted death rates by year, province, and province and year. RESULTS: A total of 50,357 CABG cases were studied, with an overall death rate of 3.6%. A national trend of decreasing mortality was found, with a risk-adjusted death rate of 3.8% in 1992/93 versus 3.2% in 1995/96 (relative decrease of 17%) (p < 0.001 for difference across years). Some provinces (e.g., Alberta, Manitoba and Ontario) achieved overall declines in death rates over the study period, whereas others (e.g., British Columbia and Saskatchewan) did not. The average severity of illness of patients who underwent CABG differed considerably across provinces. Despite risk adjustment for these differences, provincial death rates varied significantly (p < 0.001). INTERPRETATION: Rates of death after CABG in Canada decreased significantly in a relatively short period. Despite this encouraging finding, there were interprovincial differences in severity of illness and risk-adjusted death rates. This finding raises the possibility of unequal access to CABG and variable quality of care for patients undergoing the surgery across Canadian provinces.

Age Factors↗
PubMed1998

Stratified testing for treatment effects with missing data.

Dawson and Lagakos (1993, Biometrics 49,1022-1032) proposed a stratified test for repeated measures data that contain missing observations. They recommended stratification based on missing data patterns and considered sufficient conditions under which the size of the test is properly retained. In this paper, we point out some practical problems with these conditions and illustrate them with their CD4 count example as well as a stimulation study. We give a less stringent condition and delineate its merit. We also discuss what to do when none of the conditions are met.

Biometry↗
PubMed1997

Dependence of the anti-chaperone activity of protein disulphide isomerase on its chaperone activity.

Protein disulphide isomerase (PDI) shows chaperone and anti-chaperone activities in assisting refolding of denatured and reduced lysozyme in redox Hepes buffer, but only chaperone activity in phosphate buffer and redox Hepes buffer containing 0.1 M NaCl. In non-redox Hepes buffer its anti-chaperone activity is very weak. PDI displays its anti-chaperone activity only for those substrates showing relatively low aggregation during refolding, and is strongly dependent on refolding conditions, of which ionic strength appears to be an important factor. The S-methylated PDI, fully active as a chaperone but devoid of isomerase activity, by itself shows only anti-chaperone activity, but reinforces rather than suppresses the chaperone activity of native PDI in the refolding of lysozyme. A fragment of PDI with the C-terminal peptide-binding sequence removed and devoid of chaperone activity does not show anti-chaperone activity in lysozyme refolding. It appears that the anti-chaperone activity of PDI is dependent on its chaperone activity.

Animals↗
PubMed1997

Testing for treatment differences with dropouts present in clinical trials--a composite approach.

A major problem in the analysis of clinical trials is missing data from patients who drop out of the study before the predetermined schedule. In this paper we consider the situation where the outcome measure is a continuous variable and the final outcome at the end of the study is the main interest. We argue that the hypothetical complete-data marginal mean averaged over the dropout patterns is not as relevant clinically as the conditional mean of the completers together with the probability of completion or dropping out of the trial. We first take the pattern-mixture modelling approach to factoring the likelihood function, then direct the analysis to the multiple testings of a composite of hypotheses that involves the probability of dropouts and the conditional mean of the completers. We review three types of closed step-down multiple-testing procedures for this application. Data from several clinical trials are used to illustrate the proposed approach.

Bias↗
PubMed1997

Mutant human protein disulfide isomerase assists protein folding in a chaperone-like fashion.

Human protein disulfide isomerase with an extra 10 amino acid residues of AEITRIDPAM at the N-terminal was expressed in E. coli as a soluble protein comprising 20% of total cell proteins, and was purified to near homogeneity through one step of DEAE-Sephacel chromatography. The mutant enzyme, which had the same CD spectrum and comparable disulfide isomerase and thiol-protein oxidoreductase activities with that of the wild type human and bovine protein disulfide isomerases, also showed chaperone-like activity in stimulating the refolding of proteins containing no disulfide bond. The overall yield of the active product is about 20 mg 1-1 culture.

Amino Acid Sequence↗
PubMed1997

Does DsbA have chaperone-like activity?

DsbA showed chaperone-like activity similar to but weaker than that of protein disulfide isomerase in increasing reactivation and decreasing aggregation during the refolding of guanidine hydrochloride-denatured D-glyceraldehyde-3-phosphate dehydrogenase and rhodanese. The fact that both enzymes are devoid of disulfide bonds indicates the independence of the chaperone-like activity of DsbA from its thiol-protein oxidoreductase activity. The increased reactivation of D-glyceraldehyde-3-phosphate dehydrogenase by DsbA can be suppressed with increasing concentrations of a peptide of 21 amino acid residues, suggesting that the peptide binding ability of DsbA is responsible for its chaperone-like activity.

Glyceraldehyde-3-Phosphate Dehydrogenases↗
PubMed1997

Some statistical methods for multiple endpoints in clinical trials.

This paper summarizes, defines, and discusses multiple endpoints comparison procedures, concepts, and methodologies for applications to clinical trials. We address the more widely used methods of alpha-level, p-value, and critical value adjustments. We examine global assessment measures such as O'Brien's test and Simes' procedure and contrast them with the alpha-adjustment procedures of Bonferroni and Holm. We propose a global assessment procedure based on categorization of the individual endpoints to form an overall composite endpoint. Additionally, we discuss a new weighting scheme for Holm's sequentially rejective alpha-adjustment procedure. Investigation of the correlation between endpoints is examined in relation to adjustment of the alpha-level. In the context of a clinical trial, the above multiplicity procedures are applied and compared. Finally, some comments concerning ease of use and relevance are summarized for the above methods.

Asthma↗
PubMed1996

Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity.

Helicobacter pylori is involved in gastritis, gastric and duodenal ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Earlier studies already suggested a role for autoimmune phenomena in H. pylori-linked disease. We now report that lipopolysaccharides (LPS) of H. pylori express Lewis y, Lewis x, and H type I blood group structures similar to those commonly occurring in gastric mucosa. Immunization of mice and rabbits with H. pylori cells or purified LPS induced an anti-Lewis x or y or anti-H type I response, yielding antibodies that bound human and murine gastric glandular tissue, granulocytes, adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma cells. Experimental oral infections in mice or natural infection in humans yielded anti-Lewis antibodies also. The beta chain of gastric (H+,K+)-ATPase, the parietal cell proton pump involved in acid secretion, contained Lewis y epitopes; gastric mucin contained Lewis x and y antigenic determinants. Growth in mice of a hybridoma that secretes H. pylori-induced anti-Lewis y monoclonal antibodies resulted in histopathological evidence of gastritis, which indicates a direct pathogenic role for anti-Lewis antibodies. In conclusion, our observations demonstrate that molecular mimicry between H. pylori LPS and the host, based on Lewis antigens, and provide understanding of an autoimmune mechanism for H. pylori-associated type B gastritis.

Animals↗
PubMed1996

Intra-atrial myxomas, clinical-pathologic correlation based on two case studies including historical review.

The two cases of left-sided myxomas are reported with both patients having had uneventful cardiac surgery. One patient had an uneventful recovery and is doing well, whereas the second patient (female) had a complicating cerebrovascular accident. This patient was thought to have myxoma embolization; however, histopathologic verification could not be obtained. This latter patient had of course a higher risk of developing thromboembolization, due to the concomitant valve surgery procedure. The clinical, operative and pathologic studies confirm the lesions as primary myxomas and support and amplify the diagnostic concept of those lesions being of neoplastic nature, and countermand the previously commonly held concept of the thrombotic nature of myxomas. The nature of the myxoma is the primitive mesenchymal vasoformative cells of the atrial subendocardium, which is equivalent to the subendocardial cushion cell.

Female↗
PubMed1996

Assessing reproducibility by the within-subject coefficient of variation with random effects models.

In this paper we consider the use of within-subject coefficient of variation (WCV) for assessing the reproducibility or reliability of a measurement. Application to assessing reproducibility of biochemical markers for measuring bone turnover is described and the comparison with intraclass correlation is discussed. Both maximum likelihood and moment confidence intervals of WCV are obtained through their corresponding asymptotic distributions. Normal and log-normal cases are considered. In general, WCV is preferred when the measurement scale bears intrinsic meaning and is not subject to arbitrary shifting. The intraclass correlation may be preferred when a fixed population of subjects can be well identified.

Aged↗
PubMed1995

Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group.

BACKGROUND: Postmenopausal osteoporosis is a serious health problem, and additional treatments are needed. METHODS: We studied the effects of oral alendronate, an aminobisphosphonate, on bone mineral density and the incidence of fractures and height loss in 994 women with postmenopausal osteoporosis. The women were treated with placebo or alendronate (5 or 10 mg daily for three years, or 20 mg for two years followed by 5 mg for one year); all the women received 500 mg of calcium daily. Bone mineral density was measured by dual-energy x-ray absorptiometry. The occurrence of new vertebral fractures and the progression of vertebral deformities were determined by an analysis of digitized radiographs, and loss of height was determined by sequential height measurements. RESULTS: The women receiving alendronate had significant, progressive increases in bone mineral density at all skeletal sites, whereas those receiving placebo had decreases in bone mineral density. At three years, the mean (+/- SE) differences in bone mineral density between the women receiving 10 mg of alendronate daily and those receiving placebo were 8.8 +/- 0.4 percent in the spine, 5.9 +/- 0.5 percent in the femoral neck, 7.8 +/- 0.6 percent in the trochanter, and 2.5 +/- 0.3 percent in the total body (P < 0.001 for all comparisons). The 5-mg dose was less effective than the 10-mg dose, and the regimen of 20 mg followed by 5 mg was similar in efficacy to the 10-mg dose. Overall, treatment with alendronate was associated with a 48 percent reduction in the proportion of women with new vertebral fractures (3.2 percent, vs. 6.2 percent in the placebo group; P = 0.03), a decreased progression of vertebral deformities (33 percent, vs. 41 percent in the placebo group; P = 0.028), and a reduced loss of height (P = 0.005) and was well tolerated. CONCLUSIONS: Daily treatment with alendronate progressively increases the bone mass in the spine, hip, and total body and reduces the incidence of vertebral fractures, the progression of vertebral deformities, and height loss in postmenopausal women with osteoporosis.

Aged↗
PubMed1995

Independence of the chaperone activity of protein disulfide isomerase from its thioredoxin-like active site.

Protein disulfide isomerase (PDI) alkylated at thiols of the thioredoxin-like -CHC- active sites is devoid of isomerase activity, but its chaperone-like activity to increase the reactivation yield and prevent the aggregation of guanidine hydrochloride-denatured D-glyceraldehyde-3-phosphate dehydrogenase upon dilution is unimpaired. A peptide of 28 amino acids markedly inhibits both the enzyme and the chaperone activities of PDI. The above results indicate that the -CGHC- active site is necessary for the isomerase activity but not required for the chaperone activity of PDI, whereas the peptide binding site is essential for both activities.

Alkylation↗
PubMed1995

Studies of the oral bioavailability of alendronate.

Clinical studies were performed to examine the oral bioavailability of alendronate (4-amino-1-hydroxy-butylidene-1,1-bisphosphonate monosodium). All studies, with the exception of one performed in men, involved postmenopausal women. Short-term (24 to 36 hours) urinary recovery of alendronate after an intravenous dose of 125 to 250 micrograms averaged about 40% in both men and women. In women, oral bioavailability of alendronate was independent of dose (5 to 80 mg) and averaged (90% confidence interval) 0.76% (0.58, 0.98) when taken with water in the fasting state, followed by a meal 2 hours later. Bioavailability was similar in men [0.59%, (0.43, 0.81)]. Taking alendronate either 60 or 30 minutes before a standardized breakfast reduced bioavailability by 40% relative to the 2-hour wait. Taking alendronate either concurrently with or 2 hours after breakfast drastically (> 85%) impaired availability. Black coffee or orange juice alone, when taken with the drug, also reduced bioavailability (approximately 60%). Increasing gastric pH, by infusion of ranitidine, was associated with a doubling of alendronate bioavailability. A practical dosing recommendation, derived from these findings and reflective of the long-term nature of therapy for a disease such as osteoporosis, is that patients take the drug with water after an overnight fast and at least 30 minutes before any other food or beverage.

Achlorhydria↗
PubMed1994

Monitoring bone resorption in early postmenopausal women by an immunoassay for cross-linked collagen peptides in urine.

A new immunoassay using an ELISA approach for measuring urinary excretion of cross-linked N-telopeptides of type 1 collagen was evaluated as a specific measure of bone resorption. The assay was applied to 65 early postmenopausal women who participated in a placebo-controlled trial of the aminobisphosphonate, alendronate sodium. Eight blood and urine samples were collected over a 9 month interval. Baseline cross-linked peptide excretion varied from 26 to 216 pmol BCE (bone collagen/mumol Cr. Within-subject variability (CV) for cross-linked peptide excretion was 20.2% over the 9 months in placebo-treated subjects, substantially less than that observed for other biochemical markers of bone resorption: 45, 53, and 63% for fasting urinary calcium and hydroxyproline and 24 h urinary lysylpyridinoline (HPLC assay), respectively. Baseline cross-linked peptide excretion correlated significantly (p < 0.001) with baseline total urine lysylpyridinoline and serum osteocalcin, but not with the other biochemical markers. Initial peptide excretion also correlated inversely with lumbar spine bone mineral density at entry (r = -0.26, p < 0.05). Treatment for 6 weeks with alendronate produced a dose-dependent suppression of cross-linked peptide excretion (0 +/- 8, 29 +/- 6, 56 +/- 5, and 64 +/- 3% for 0, 5, 20, and 40 mg, respectively, p < 0.01 versus placebo for treatment effect), with a return toward pretreatment values during follow-up. Measurement of the urinary cross-linked N-telopeptides of type I collagen by this new ELISA approach appears promising as a simple and reliable method to assess overall bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Alendronate↗