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N L Young

Publications and source records attributed to N L Young.

At least 19 recordsLinked to original sources

A comparison of different indices of responsiveness.

The first purpose of this study was to determine if different indices of responsiveness provided similar rank orderings of scales in terms of responsiveness. The second purpose was to compare the responsiveness of patient-specific, disease-specific, and generic health status measures for patients undergoing total hip arthroplasty. All patients of one surgeon at a single institution were eligible for the study. Patients who did not speak English or did not return for post-operative evaluations were excluded. Patients completed two disease-specific scales (the Harris Hip Scale and the Western Ontario and McMaster osteoarthritis scale or WOMAC), one generic health status scale (the SF-36), and two patient-specific scales (the McMaster-Toronto Arthritis questionnaire or MACTAR and the Patient Specific Index or PASI). All scales were administered on two occasions: before and 6 months after total hip arthroplasty. Responsiveness was measured using: (1) the responsiveness statistic; (2) standardized response mean; (3) relative efficiency statistic; (4) effect size; and also by (5) correlating each scale's change score with the change in patients' global ratings of their "hip function." Seventy-eight sequential patients completed the study. The mean age was 62 years (range 25-87), 55% were male, and 71% had osteoarthritis. Test-retest reliability of the scales ranged from 0.31 to 0.93. The correlation among scales was consistent with a priori hypotheses confirming construct validity of the scales. Although the disease-specific scales were generally rated as the most responsive scales, the different indices provided different rank orderings by up to 5 levels (p = 0.04). In conclusion, disease-specific scales are the most responsive scales. However, choosing among scales based on responsiveness must be done with caution because different indices of responsiveness provide different rank ordering.

Adult

Antimicrobial susceptibilities of strains of Neisseria gonorrhoeae in Bangkok, Thailand: 1994-1995.

BACKGROUND AND OBJECTIVES: Failure of uncomplicated gonococcal infections acquired in the Far East to respond to doses of ciprofloxacin and ofloxacin recommended by the Centers for Disease Control and Prevention have been identified in Australia, the United Kingdom, and the United States. In the Republic of the Philippines, 54.3% of strains exhibited decreased susceptibility to fluoroquinolones; 12% of strains were resistant to ciprofloxacin. This study was undertaken to compare the antimicrobial susceptibilities of gonococcal isolates in Bangkok, Thailand, with those in the Republic of the Philippines. GOAL: To determine the frequency and diversity of antimicrobial resistance, particularly to fluoroquinolones, in gonococcal strains in Bangkok, Thailand. STUDY DESIGN: Strains of Neisseria gonorrhoeae isolated from 101 patients with uncomplicated gonorrhea in Bangkok, Thailand, in July, 1994 (46 strains) and November, 1994 to July, 1995 (55 strains), were characterized by auxotype/serovar class, antimicrobial susceptibilities, and plasmid profile. Susceptibilities were determined to penicillin G, tetracycline, ceftriaxone, cefixime, cefoxitin, ciprofloxacin, ofloxacin, norfloxacin, erythromycin, kanamycin, and thiamphenicol. RESULTS: Of 101 strains, 89.1% (90/101) were resistant to penicillin or tetracycline. Plasmid-mediated resistance to penicillin or tetracycline was identified in 33.7% (34/101) of the isolates: penicillinase-producing Neisseria gonorrhoeae (17.8%; 18/101), tetracycline-resistant Neisseria gonorrhoeae (7.9%; 8/101), and penicillinase-producing/tetracycline-resistant Neisseria gonorrhoeae (7.9%; 8/101). Most penicillinase-producing strains (96.2%; 25/26) possessed the 4.4-megadalton (Md) beta-lactamase plasmid; one strain possessed the 3.2-Md beta-lactamase plasmid. Chromosomally mediated resistance to penicillin and tetracycline was exhibited by 51.5% (52/101) of strains, and 4.0% (4/101) were tetracycline resistant. All strains were susceptible to spectinomycin. Of 21.8% (22/101) strains exhibiting decreased susceptibility to ciprofloxacin (minimal inhibitory concentration [MIC] > or = 0.125 microgram/ml), one strain (ciprofloxacin MIC, 0.5 microgram/ml; ciprofloxacin inhibition zone diameter of 23 mm) had MICs of 2.0 and 8.0 micrograms/ml for ofloxacin and norfloxacin, respectively, indicating resistance to these agents. Decreased susceptibility to ciprofloxacin was identified in strains with chromosomally mediated resistance to penicillin or tetracycline and in penicillinase-producing strains. CONCLUSIONS: In Bangkok, Thailand, gonococcal isolates exhibit resistance to penicillin, tetracycline, kanamycin, and thiamphenicol. Decreased susceptibility to fluoroquinolones is emerging in a variety of strains of N. gonorrhoeae. Thus, all gonococcal infections should be treated with antimicrobial therapies known to be active against all gonococcal strains to reduce the spread of strains exhibiting decreased susceptibilities to fluoroquinolones.

Anti-Bacterial Agents

The context of measuring disability: does it matter whether capability or performance is measured?

This study assesses the differences between two methods of conceptually framing physical disability questions, using two scenarios (capability and performance). The relationship between capability and performance was explored on the basis of the literature and empirically tested by administering two versions of the Activities Scale for Kids (ASK) to 28 physically disabled children. The capability version asked children what they "could do," whereas the performance version asked what they "did do." Capability was found to exceed performance (p < 0.001) by approximately 18%. The difference may relate to a difference in environmental contexts between the two versions, with performance reflecting abilities in usual (or real life) circumstances and capability reflecting abilities in a defined situation apart from real life. Researchers must, therefore, consider carefully the environmental circumstances in which they wish to evaluate outcomes, and use this information to decide whether to measure capability, performance, or both.

Activities of Daily Living

HIV-1 subtypes and male-to-female transmission in Thailand.

We examined the risk factors for heterosexual transmission of HIV in a case-control study of couples in Thailand. 90 HIV-positive men and their regular sex partners were enrolled at the immune clinic, Chulalongkorn Hospital, where 92% of male index cases had HIV-1 serotype A (subtype E). Most index cases had acquired HIV through sexual intercourse. 95 couples were enrolled at 15 detoxification clinics, where 79% of them had HIV-1 serotype B (subtype B). Most men had acquired HIV through injecting drug use (IDU).

Case-Control Studies

Reported use of strategies by surgeons to prevent transmission of bloodborne diseases.

OBJECTIVE: To determine how often surgeons use strategies to prevent the transmission of bloodborne diseases and what factors are associated with the use of these strategies. DESIGN: Cross-sectional mail survey. SETTING: Secondary and tertiary care teaching hospitals affiliated with the University of Toronto. PARTICIPANTS: Of 539 active surgical staff and residents who were eligible, 503 (93.3%) responded. OUTCOME MEASURES: Current preventive practices, attitudes toward transmission of bloodborne diseases, perceived risk of infection and willingness to adopt preventive strategies. RESULTS: On average, surgeons reported using double- or triple-gloving in 32.2% of procedures, facial protection (including regular corrective eyewear) in 74.2% and goggles or face shields in 19.4%. Use of strategies to prevent sharp injuries, in addition to barrier precautions, was reported by 259 (51.5%) of the respondents. Factors associated with greater use of preventive strategies included resident position, subspecialty, greater number of years in surgical practice and a high perceived risk. Most of the respondents thought that patients should be routinely screened for HIV antibodies before surgery (68.2% [343/503]), that there was too little research into ways to reduce the risk of transmission of bloodborne diseases (55.3% [278/503]) and that there was too little effort on the part of organizations to reduce the risk of transmission (58.8% [296/503]). The perceived lifetime risk was reported to be moderate or high by 191 (38.0%) of the respondents and low or insignificant by 308 (61.2%). In all, 463 (92.0%) indicated a willingness to change the way they performed surgery to prevent transmission of bloodborne diseases. CONCLUSION: Surgeons expressed varying degrees of concern about the transmission of bloodborne diseases and reported infrequent use of preventive strategies. Efforts to reduce the risk of transmission between patients and surgeons will need to include informing surgeons of their personal risk and the availability of preventive strategies, improving the comfort of barrier precautions and minimizing how preventive strategies interfere with surgery.

Adult

The role of children in reporting their physical disability.

OBJECTIVE: To explore the contributions of children during the development of a disability scale, and their competence using the new scale. DESIGN: A new self-report measure of pediatric physical performance, the Activities Scale for Kids (ASK), was developed based on interviews and pilot testing with children. The ASK was then filled out by children on two occasions 2 weeks apart to assess the reliability of child self-report. Validity was assessed by comparison of interview data and ASK scores from children with similar data collected from their parents, and to clinician and family global ratings of disability. SETTING: The study was conducted at a pediatric tertiary care hospital and its affiliated rehabilitation center. PATIENTS: All subjects, 5 to 15 years of age, experienced activity limitations because of musculoskeletal disorders and were free of cognitive impairment. Thirty children (mean age, 11.5 years) participated in the development of the ASK, and 28 children (mean age, 11.4 years) participated in testing of reliability and validity. RESULTS: Children generated items similar to those generated by parents (85% agreement) and identified 10 items not obtained from parents or the literature. Children demonstrated excellent test-retest reliability (intraclass correlation coefficient [ICC] = .97) using the ASK, and their scores were highly concordant with parent-reported ASK scores (ICC = .96). Validity was ascertained by comparison of ASK scores across different levels of disability based on global ratings of families and clinicians (p = .0023). CONCLUSION: Children are able to play an important role in pediatric physical disability evaluation.

Adolescent

Determination of HIV-1 subtypes in injecting drug users in Bangkok, Thailand, using peptide-binding enzyme immunoassay and heteroduplex mobility assay: evidence of increasing infection with HIV-1 subtype E.

OBJECTIVES: To evaluate the sensitivity and specificity of peptide-binding enzyme immunoassay (PEIA) and heteroduplex mobility assay (HMA) for the determination of HIV-1 subtypes B and E; to determine the proportions of infections due to subtypes B and E over time; and to generate data on DNA sequences of the C2-V3 region of the env genes. METHODS: HIV-1 subtyping was conducted by PEIA and HMA on blood specimens obtained from 97 injecting drug users (IDU) infected with HIV between 1988 and 1993. Genetic sequencing was performed on 84 specimens. RESULTS: Both laboratory methods were highly sensitive and specific for the determination of HIV-1 subtypes B and E. The two tests were complementary; samples which could not be typed by HMA were correctly typed by PEIA and vice versa. While subtype B accounted for 80.4% (78 out of 97) of infections overall, the proportion of new infections due to subtype E increased from 2.6% (one out of 38) in 1988-1989 to 25.6% (11 out of 43) in 1990-1991, and to 43.8% (seven out of 16) in 1992-1993 (chi 2 for linear trend, P < 0.001). CONCLUSIONS: HMA and PEIA are practical, sensitive and specific laboratory methods for the determination of HIV-1 subtypes in Thailand, and may be useful in other geographic areas to define the molecular epidemiology of the global HIV-1 pandemic. Data suggest that the proportion subtype E infections have increased among Bangkok IDU from 1988 through 1993.

Adult

Independent introduction of two major HIV-1 genotypes into distinct high-risk populations in Thailand.

To investigate the genetic heterogeneity and epidemiological distribution of human immunodeficiency virus type 1 (HIV-1) in Thailand, we determined proviral sequences for 63 HIV-1-infected patients in various risk groups from all over the country between April and July, 1991. Two distinct genotypes of HIV-1, A and B, were found to segregate by mode of transmission. Of 29 sexually infected patients, 25 (86%) had HIV-1 of genotype A and 4 (14%) had genotype B. Among 29 injecting drug users, probably parenterally infected, only 7 (24%) had genotype A and 22 (76%) had genotype B. This segregation is unlikely to have arisen by chance (p < 0.001). No patient was found to have dual infection. Nucleotide divergence averaged 3.4% among genotype-A-infected patients and 3.5% among genotype-B-infected patients, but 22.0% between the genotypes. 37 of 40 isolates (both genotypes) had the GPGQ tetrapeptide at the tip of the V3 loop, which is common in African HIV-1 strains but rare in North American and European strains, where the GPGR motif predominates. These findings suggest that the waves of HIV-1 infection in injecting drug users and in sexually infected patients in Thailand may not be epidemiologically linked. The nucleotide divergence data point to the separate introductions of the two genotypes in Thailand. Further studies in Thailand and neighbouring countries will be useful in the design and selection of candidate HIV vaccines.

Amino Acid Sequence

The effects of norepinephrine and nutritional status on resting metabolic rates in the LA/N-cp rat.

1. The effects of diet and norepinephrine (NE) on resting metabolic rate (RMR) were determined using indirect calorimetry in 6-month-old lean and corpulent LA/N-cp rats. RMRs of lean rats were greater than the corpulent. 2. Ingestion of carbohydrate (CHO) in the unfasted and fasted states increased the RMR of both groups, especially in the lean phenotype when compared to oil. 3. Serum T3 and glucose concentrations were similar in both phenotypes. 4. The effects of NE on RMR were maximal after a 200 micrograms NE/kg body weight injections.

Animals

Contributions of absorbed dietary cholesterol and cholesterol synthesized in small intestine to hypercholesterolemia in diabetic rats.

To determine how insulin deficiency leads to hypercholesterolemia, we examined cholesterol absorption, synthesis, and utilization in streptozocin-induced diabetic rats fed a grain-based diet ad libitum. Absorbed dietary cholesterol was determined from measurement of dietary cholesterol intake and previous data for cholesterol fractional absorption. Daily rates of cholesterol synthesis in the small intestine, liver, and periphery were calculated from recovery of labeled sterols after injection of 3H2O at six times during 24 h. Utilization of cholesterol for growth, fecal excretion, and bile acid synthesis were also determined. Absorbed dietary cholesterol in diabetic rats was double that in control rats. The contribution of absorbed cholesterol to total cholesterol production (sum of absorbed dietary cholesterol) and endogenous cholesterol synthesis) in control rats was 24% compared to 48% in diabetic rats. The increase in diabetic rats was due to overeating and, to a lesser extent, to increased fractional absorption. Overeating also induced intestinal hypertrophy and a twofold increase in cholesterol synthesis by the small intestine to 24% of whole-body production in diabetic rats. Consequently, the small intestine accounted for 72% of daily cholesterol input in diabetic rats compared to 37% in control rats, with diet accounting for two-thirds of the cholesterol input via the small intestine in both groups. In response to this increased input from the intestine, cholesterol synthesis in the periphery was 39% of whole-body production in control rats compared to 22% in diabetic rats, and synthesis in the liver was 26 and 6% of total cholesterol production in control and diabetic rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Plasma very low density lipoproteins contain a single molecule of apolipoprotein B.

Rat and human very low density lipoproteins (VLDL) were fractionated by zonal ultracentrifugation, yielding sharply defined fractions with narrow sedimentation limits. Sedimentation coefficients for the individual fractions were determined at two densities with the analytical ultracentrifuge, and the results were analyzed to yield buoyant densities and molecular weights for the particles in each fraction. For the rat lipoproteins, the weight concentrations of triglycerides, cholesterol, phospholipid, and protein were determined for each fraction, and their molar concentrations of apolipoprotein B were measured with a radioimmunoassay. For the human lipoproteins the corresponding values were taken from Patsch et al. (Patsch, W., J. R. Patsch, G. M. Kostner, S. Sailer, and H. Braunsteiner. 1978. Isolation of subfractions of human very low density lipoproteins by zonal ultracentrifugation. J. Biol. Chem. 253:4911-4915). From these data, a ratio of the number of apoB peptides to the number of lipoprotein particles was calculated for each fraction. This ratio was close to 1 for all VLDL fractions, ranging in particle diameter from about 40 to 80 mm and 30 to 50 mm, respectively, for rat and human VLDL. The majority rat VLDL contain B-48 rather than B-100 as their (single) apoB peptide. Based on these data, we proposed that only a single copy of B-48 is required for VLDL assembly in rat liver, unless nascent hepatic VLDL contain additional apoB peptides which are uniformly lost from the plasma VLDL particles when they are analyzed.

Amino Acids

Radioimmunoassay of rat apolipoprotein B peptides in lipoproteins and tissues.

Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) separates rat apolipoprotein B (apoB) into one lower and two higher molecular weight components. Of the latter, peptide I (PI) corresponds to human B-100, while the slightly faster-migrating peptide II (PII) lacks a human counterpart; the smaller species peptide III (PIII) corresponds to human B-48. We describe here a competitive radioimmunoassay which separately measures the amounts of total (i.e., PI + PII + PIII) and larger (i.e., PI + PII) rat apoB peptides, with the amounts of PIII obtained by difference. Standard rat PIII and combined PI + PII (PI,II) were isolated by high-pressure gel filtration liquid chromatography in the presence of SDS, and the PI,II was used as an immunogen to raise rabbit antisera which were capable of binding all three forms of rat apoB. However, Scatchard analysis showed this binding to represent two distinct types of antibodies: one high-affinity class which bound only PI,II and a second class which bound all apoB peptides with equal but lower affinity. Thus, since 125I-labeled PIII was displaced equally effectively by PI,II and PIII, but 125I-labeled PI,II was displaced only by PI,II, the unabsorbed antiserum could be used to measure either total apoB or PI,II alone, depending on the choice of labeled ligand. The validity of the assay for apoB peptides in very-low-density and low-density lipoproteins and in liver microsomes was verified by comparison with peptide determinations by SDS-PAGE.

Animals

Regulation of indices of cholesterol synthesis in human mononuclear leukocytes by dietary cholesterol and fat saturation.

The responses of 2 indices of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-CoA reductase activity and incorporation of [14C]acetate into sterols, in mononuclear leukocytes freshly isolated from peripheral blood to variation in the ratio of saturated to unsaturated fat (S:U) and the amount of cholesterol absorbed from the diet were examined in 24 free-living men. Increasing S:U was associated with increasing plasma cholesterol level (r = 0.27, P = 0.03) and increasing reductase activity in leukocytes (r = 0.60, p less than 0.001). This finding is consistent with the hypothesis that saturated fat decreases the flux of cholesterol from plasma into cells thereby releasing reductase from product feedback inhibition. Reductase activity, after controlling for the effect of S:U, was negatively correlated with absorbed cholesterol from sources other than eggs (r = 0.42, P = 0.02). Surprisingly, change in reductase activity was positively correlated with change in absorbed cholesterol upon eating eggs (r = 0.49, P = 0.008). Sterol labeling was negatively correlated with absorbed cholesterol from all sources including eggs (r = -0.64, P less than 0.001) and was uncorrelated with S:U. Reductase activity and sterol labeling responded in parallel to cholesterol in foods other than eggs but not to egg feeding nor to S:U, thus it is unclear which test best reflects endogenous sterol synthesis in these cells.

Cholesterol

Evaluation of the contribution of dietary cholesterol to hypercholesterolemia in diabetic rats and of sitosterol as a recovery standard for cholesterol absorption.

The contribution of dietary cholesterol to hypercholesterolemia in diabetic rats fed chow ad libitum was evaluated. Diabetes was induced with streptozotocin, and the intake, absorption, and subsequent tissue distribution of dietary cholesterol were measured. Absorption was measured as the difference between [3H]cholesterol intake and fecal 3H-labeled neutral sterol excretion, using both [14C]sitosterol (added to diet) and [14C]cholesterol (added to feces) as recovery markers. [3H]Cholesterol absorption was underestimated by 1-3% using [14C]sitosterol as a recovery standard, due to the 7-8% absorption of sitosterol. After 3 weeks of diabetes, rats were hyperphagic, thereby increasing dietary cholesterol intake 2-fold. [3H]Cholesterol absorption was significantly increased from 69% in controls to 78% in diabetics, whereas [14C]sitosterol absorption was unaffected. With increased dietary cholesterol intake and decreased whole body cholesterol synthesis (Diabetes. 1983. 32: 811-819), influx from diet equaled for exceeded influx from synthesis. The amounts of 3H-labeled neutral sterol recovered from the small intestine, periphery, and plasma were increased 3- to 4-fold in the diabetic rats. Furthermore, the degree of hypercholesterolemia in diabetic rats was directly related to the fraction of plasma cholesterol derived from the diet. We conclude that the 2.3-fold increase in absorbed dietary cholesterol resulting from hyperphagia and, to a lesser extent, from increased fractional absorption, contributes to the hypercholesterolemia of diabetic rats fed chow ad libitum.

Animals

Hyperphagia alters cholesterol dynamics in diabetic rats.

Rats with streptozotocin-induced diabetes stop growing and start eating more chow. These two events elicit an interacting series of changes in cholesterol dynamics. Hyperphagia increases dietary cholesterol intake and cholesterol synthesis by the small intestine. These increases are balanced by a decrease in cholesterol synthesis in the rest of the body so that total cholesterol input is normal. With growth failure, utilization of cholesterol for formation of new tissue ceases. This decrease is balanced by an increase in bile acid synthesis by the liver. The bile acid pool in the contents of the small intestine is enlarged by hyperphagia. Despite these changes, fecal sterol excretion and total utilization of cholesterol are normal. During the course of changes in growth and food intake and the attendant changes in cholesterol flux, the total tissue cholesterol pool does not change. Therefore influx equals efflux and the systems regulating cholesterol and bile acid synthesis are responding appropriately and are themselves unperturbed by insulin deficiency. However, plasma cholesterol level increases threefold. This elevation is due to increased influx of cholesterol from the small intestine and decreased synthesis in the rest of the body, so that a larger portion of total body cholesterol influx passes through the blood.

Animals