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Biomedical subjects

S R Smith

Publications and source records attributed to S R Smith.

At least 91 records · Page 5Linked to original sources

Low-dose T(3) improves the bed rest model of simulated weightlessness in men and women.

This study tested the hypothesis that low-dose 3,5, 3'-triiodothyronine (T(3)) administration during prolonged bed rest improves the ground-based model of spaceflight. Nine men (36.4 +/- 1. 3 yr) and five women (34.2 +/- 2.1 yr) were studied. After a 5-day inpatient baseline period, subjects were placed at total bed rest with 6 degrees head-down tilt for 28 days followed by 5-day recovery. Fifty micrograms per day of T(3) (n = 8) or placebo (n = 6) were given during bed rest. Serum T(3) concentrations increased twofold, whereas thyroid-stimulating hormone was suppressed in treated subjects. T(3)-treated subjects showed significantly greater negative nitrogen balance and lost more weight (P = 0.02) and lean mass (P < 0.0001) than placebo subjects. Protein breakdown (whole body [(13)C]leucine kinetics) increased 31% in the T(3) group but only 8% in the placebo group. T(3)-treated women experienced greater changes in leucine turnover than men, despite equivalent weight loss. Insulin sensitivity fell by 50% during bed rest in all subjects (P = 0.005), but growth hormone release and insulin release were largely unaffected. In conclusion, addition of low-dose T(3) to the bed rest model of muscle unloading improves the ground-based simulation of spaceflight and unmasks several important gender differences.

Adult↗

Testosterone administration preserves protein balance but not muscle strength during 28 days of bed rest.

Decrements in muscle strength as a result of prolonged bed rest are well defined, but little is known about potential countermeasures for preventing loss of strength under this condition. The purpose of this study was to determine whether testosterone administration would preserve protein balance and muscle strength during prolonged bed rest. Ten healthy men (age, 36 +/- 2 yr; height, 177.2 +/- 3.4 cm; weight, 80.5 +/- 3.9 kg; mean +/- SE) were admitted to our in-patient metabolic unit. After a 1-week ambulatory run-in period, each subject was confined to bed for 28 days at 6 degree head-down tilt while receiving a daily oral dose of T3 (50 microg/day). During the bed rest/T3 period, six of the men were randomized to receive testosterone enanthate by i.m. injection (T; 200 mg/week) while four received placebo in a double blind fashion. Nitrogen balance was determined throughout, and whole body [13C]leucine kinetics were assessed at baseline and on day 26 of bed rest. Before bed rest and on the third day of reambulation, the muscle strength of the knee extensors and flexors and shoulder extensors and flexors was determined at 60 degrees/s on a Cybex isokinetic dynamometer. Despite improved [13C]leucine kinetics and maintenance of nitrogen balance and lean body mass in T-treated subjects, little preservation of muscle strength, particularly in the knee extensors, was noted. Muscle strength [reported as the best work repetition in foot-pounds (FtLb)] for right knee extensors declined (P = 0.011) similarly in both groups; from 165 +/- 15 to 126 +/- 18 FtLb in T-treated men and from 179 +/- 22 to 149 +/- 13 FtLb in placebo-treated men. Overall, there was less of a decline in extension and flexion strength of the shoulder compared to the knee, with no benefit from T. These results suggest that in the absence of daily ambulatory activity, T administration will not increase or, in the case of this bed rest model, preserve muscle strength.

Adult↗

Nonprescription and alternative medication use by individuals with HIV disease.

OBJECTIVE: To examine the strength of the associations between predisposing, enabling, and need-for-care variables and the self-treatment of HIV disease; and to compare sociodemographic and illness-related factors associated with the use of vitamins, nonprescription medications, herbs, and recreational substances among HIV-infected individuals. METHODS: Data were derived from 7887 interviews conducted as part of the AIDS Cost and Services Utilization Survey. The conceptual framework was the Andersen Behavioral Model of Health Services Use. Factors associated with nonprescription and alternative medication use were assessed using logistic regression. Generalized estimating equations were applied to adjust variance estimates for within-person correlations of drug use over time. RESULTS: After adjusting for perceived health status, T cell count, and stage of disease, the results indicated that African-Americans were less likely to use nonprescription drugs (odds ratio [OR] 0.65, 95% CI 0.52 to 0.81), vitamins (OR 0.59, 95% CI 0.48 to 0.73), and herbs (OR 0.41, 95% CI 0.22 to 0.76), compared with non-Hispanic whites. Similarly, Hispanics were less likely to report use of herbs (OR 0.58, 95% CI 0.34 to 0.98) or recreational drugs (OR 0.34, 95% CI 0.15 to 0.76) than were non-Hispanic whites. Oppositely, individuals who had a college education were more likely to use vitamins (OR 1.26, 95% CI 1.05 to 1.50) and herbs (OR 2.47, 95% CI 1.56 to 3.91). Enabling variables such as insurance status and income were generally associated only with use of recreational drugs. Need-for-care variables were generally associated only with use of nonprescription drugs and vitamins. CONCLUSIONS: Predisposing, enabling, and need-for-care variables from the Andersen Behavioral Model were significantly associated with the use of four categories of drugs to self-treat HIV disease. However, there was not a consistent pattern across the drug categories.

Adolescent↗

The clinical utility of the MMPI-2 Antisocial Practices Content Scale.

This study explored the ability of the MMPI-2 Antisocial Practices Content Scale (ASP) to correctly classify DSM-IV Antisocial Personality Disorder (APD). ASP scores and scores on the MMPI-2 Psychopathic Deviate (Pd) scale were compared in an APD group (n = 10), a Borderline Personality Disorder group (n = 16), a Narcissistic Personality Disorder group (n = 9), an Other Personality Disorder group (representing personality disorders from Clusters A and C; n = 14), and a nonclinical population (NC; n = 67). The ASP exhibited an ability to differentiate APD from other personality disorders and was significantly correlated to DSM-IV diagnostic criteria for APD while the Pd was not. Diagnostic efficiency statistics (sensitivity, specificity, positive predictive power, negative predictive power, overall correct classification rate, and kappa) were calculated under four different conditions in a clinically relevant manner (Kessel & Zimmerman, 1993. Psychological Assessment, 53, 395-399). The results of this study illustrate the usefulness of the ASP as a tool for the assessment of antisocial attitudes, beliefs, and behaviors in individuals suspected of having APD. This information may be valuable to clinicians who are planning treatment or assessing treatment outcome for clients with APD.

Adult↗

Access and use of medications in HIV disease.

OBJECTIVE: To examine if measures of access to medical care are associated with outpatient use of antiretroviral and Pneumocystis carinii pneumonia (PCP) medications among a cohort of individuals with HIV disease. DATA SOURCES: Adults who participated in a series of up to six interviews as part of the AIDS Costs and Services Utilization Survey (ACSUS). ACSUS, a panel survey of persons with HIV disease, was undertaken from 1991 through 1992. STUDY DESIGN: The Andersen Behavioral Model of Health Services Use provided the conceptual framework for the study. Logistic regression analyses with generalized estimating equations were conducted to determine the effects of predisposing, enabling, and need-for-care factors on the odds of antiretroviral or PCP medication use. The analytic sample consisted of 1,586 respondents whose 7,652 interviews provided the data. PRINCIPAL FINDINGS: The multivariate analysis showed that being female (OR = 0.76; 95% C.I. = 0.60-0.95), ages 15 to 24 years (OR = 0.64; 95% C.I. = 0.44-0.92), and having a hospitalization (OR = 0.73; 95% C.I. = 0.63-0.84) were associated with lower odds of using antiretrovirals. African American race (OR = 1.30; 95% C.I. = 1.04-1.62), having both public and private insurance (OR = 2.11; 95% C.I. = 1.47-3.03), attending counseling (OR = 1.17; 95% C.I. = 1.02-1.34), having a usual source of care (OR = 1.70; 95% C.I. = 1.38-2.11), and clinical trials participation (OR = 1.52; 95% C.I. = 1.23-1.87) were associated with a higher odds of use. Similar results were obtained for analyses of PCP medication use. CONCLUSIONS: Sociodemographic differences exist in access and use of prescription drugs within the ACSUS cohort. The results suggest that women and those ages 15 to 24 years have poor access to some medications that improve survival in HIV disease.

Adolescent↗

Plasma myostatin-immunoreactive protein is increased after prolonged bed rest with low-dose T3 administration.

It has been hypothesized that myostatin, a newly identified member of the transforming growth factor-beta (TGF-beta) family of proteins, acts as a negative regulator of skeletal muscle growth. Because bed rest induced muscle atrophy results from a decreased rate of muscle protein synthesis, we hypothesized that circulating levels of myostatin would be increased following prolonged bed rest. Twelve men (age, 35.8 +/- 4.6 yr; height, 175.7 +/- 2.3 cm; weight, 74.8 +/- 3.5 kg; mean +/- SE) were confined to bed for 25 days at 6 degrees head-down tilt while receiving triiodothyronine (T3; 50 micrograms/day) to accelerate protein loss. Total lean body and appendicular skeletal muscle mass were determined by dual energy x-ray absorptiometry (DEXA) before and after the bed rest period. Plasma myostatin-immunoreactive protein was measured in blood samples obtained after an overnight fast 5 days prior to, and on the 25th day of bed rest. Lean body mass decreased an average 2.2 kg (p < 0.0001). Appendicular skeletal muscle accounted for a majority of the lean body mass loss. On day 25 of bed rest, plasma myostatin-immunoreactive protein was 12% higher (p = 0.01) than measured at baseline. These data support the idea that myostatin regulates muscle growth in humans and that it may be a novel target for interventions aiming to reduce space flight induced muscle atrophy.

Adult↗

Interleukin-10 dose-dependent regulation of CD4+ and CD8+ T cell-mediated graft-versus-host disease.

BACKGROUND: Endogenous interleukin (IL)-10 production has been associated with the lack of graft-versus-host disease (GVHD) in human recipients of MHC-disparate donor grafts. Paradoxically, we have shown that the exogenous administration of high doses (30 microg/dose) of IL-10 to murine recipients of MHC-disparate grafts accelerates GVHD lethality. METHODS: The effects of IL-10 on GVHD mediated by either CD4+ or CD8+ T cells was examined in studies involving exogenous IL-10 administration or the infusion of T cells from IL-10-deficient (-/-) donor mice. The role of interferon (IFN)-gamma on IL-10-induced GVHD acceleration was studied using IFN-gamma-deficient (-/-) donor mice or neutralizing monoclonal antibody. RESULTS: IL-10 was found to have a dose-dependent effect on the GVHD lethality mediated by either CD4+ or CD8+ T cells. High doses of exogenous IL-10 accelerated GVHD lethality. IFN-gamma release was not responsible for the IL-10 facilitation of GVHD lethality. Paradoxically, low doses of IL-10 protected mice against GVHD lethality. The GVHD protective effect of the bioavailability of small amounts of IL-10 was confirmed by demonstrating that the infusion of T cells from IL-10 -/- donors accelerated GVHD lethality. CONCLUSIONS: The results suggest that IL-10 has a dose-dependent effect on the GVHD lethality mediated by CD4+ or CD8+ T cells, such that high doses accelerate lethality, while low amounts of bioavailable IL-10 are protective.

Animals↗

Reliability and validity of a macronutrient self-selection paradigm and a food preference questionnaire.

Our laboratory has developed a macronutrient self-selection paradigm (MSSP) designed to vary fat content significantly and systematically with sugar, complex carbohydrates, and protein content in a battery of foods in which fat is commonly consumed in the American diet. We have also developed a food preference questionnaire (FPQ) according to an identical design but using a list of foods mutually exclusive of those presented for selection and intake in the MSSP. Men were tested twice on both instruments, with a 4-week interval between tests. It was determined that the MSSP has strong test-retest reliability for overall fat (r = 0.91) and other macronutrient intake and total caloric intake. In addition, hunger and fullness ratings were reproducible, and fat preferences (r = 0.99) and hedonic responses to foods listed on the FPQ were highly consistent across trials. This study also demonstrated that the MSSP is a valid instrument with respect to the men's reports of habitual intake of fat (r = 0.80) and total carbohydrates on the Block food questionnaire (FQ). In addition, men's fat preferences on the FPQ were validated with respect to overall fat (r = 0.86) and total caloric intake in the MSSP and fat intake (r = 0.83) reported on the Block FQ. The MSSP also has the capability to detect a wide range of fat intake (3.06-50.35% among the present subjects), indicating that this instrument can identify individuals who differ markedly in fat intake or could detect changes in fat preference within subjects. In addition, this paradigm detected a large range of sugar and total caloric intake. It is anticipated that the use of these laboratory tools can enhance our understanding of the relationship between dietary fat intake and obesity.

Adult↗

Effect of undergraduate college major on performance in medical school.

PURPOSE: To determine whether choice of college major has any effect on performance in medical school. METHOD: The author analyzed data for 406 students enrolled in a combined baccalaureate-MD program at Brown University School of Medicine who had matriculated in medical school from 1989 to 1997, determining their undergraduate majors and their medical education performances (as measured by course grades, USMLE, scores and residency program evaluation). RESULTS: Slightly over half of the students had majored in science or mathematics, about a third had majored in the humanities or social sciences, and about a tenth had had double majors or had been independent concentrators. The author found no statistically significant difference between the medical school performances of students who had majored in the sciences or mathematics and those who had majored in the humanities or the social sciences. CONCLUSION: Although preselection bias may influence medical school performance, this study affirms previous findings that choice of undergraduate major has little, if any, statistically significant effect.

Education, Medical↗

Tumescent anesthesia in ambulatory phlebectomy.

BACKGROUND: Ambulatory phlebectomy is an elegant outpatient procedure for the removal of varicose veins. One of the keys to its success is the ability to perform the procedure under local anesthesia. A new form of anesthesia, tumescent anesthesia, has been developed for liposuction surgery and is now being expanded for use in other surgical disciplines. OBJECTIVE: To determine the efficacy and safety as well as review the use and advantages of tumescent anesthesia in ambulatory phlebectomy. METHODS: A retrospective review of phlebectomy cases performed in our offices under tumescent anesthesia. RESULTS: The reported level of intraoperative and postoperative pain was very low. The complication rate was consistent with other reports except for a higher number of hematomas (3.4%). CONCLUSIONS: Tumescent anesthesia provides a very safe, comfortable method of anesthetizing patients for ambulatory phlebectomy. Epinephrine, in appropriate concentrations, should be a part of all tumescent anesthetic solutions used for phlebectomy as it may decrease the incidence of hematoma.

Ambulatory Surgical Procedures↗

Carbon monoxide mass exposure in a pediatric population.

OBJECTIVES: To describe the outcomes of a mass carbon monoxide (CO) intoxication, and to calculate the CO half-life in a pediatric school-aged population. METHODS: A retrospective chart review was performed based on Regional Poison Center database information, hospital laboratory data, and medical records of the pediatric patients who sought care at one of 3 St. Louis area hospitals, after exposure to high levels of CO. Exposures occurred on January 5, 1996, after evidence of a CO leak was discovered at an area elementary school. Charts were reviewed for major demographics, symptoms reported, carboxyhemoglobin (COHb) levels and times, and level of effect. RESULTS: Information about 177 (35%) of the 504 children in attendance at school that day was available. Mean age was 8.7 +/- 1.8 years (range 4-12 years). Symptoms were present in 155 (88%) of the 177 children for whom data were available. Initial COHb levels were obtained for 147 (83.1%) of the 177 children. First mean COHb level was 7.0% (95% CI = 6.6-7.5%). Second COHb level was obtained for 26 children with a mean of 2.7% (95% CI = 2.2-3.2%). Calculated half-life of COHb, on 100% O2 at 1 atm, was 44.0 minutes (95% CI = 39.6-48.2 minutes). CONCLUSION: Some children had symptoms at COHb levels that traditionally have been considered nontoxic. The elimination of COHb was found to be more rapid in this population of children than reported in other studies.

Carbon Dioxide↗

Identifying and defining the dimensions of community capacity to provide a basis for measurement.

Although community capacity is a central concern of community development experts, the concept requires clarification. Because of the potential importance of community capacity to health promotion, the Division of Chronic Disease Control and Community Intervention, Centers for Disease Control and Prevention (CDC), convened a symposium in December 1995 with the hope that a consensus might emerge regarding the dimensions that are integral to community capacity. This article describes the dimensions that the symposium participants suggested as central to the construct, including participation and leadership, skills, resources, social and interorganizational networks, sense of community, understanding of community history, community power, community values, and critical reflection. The dimensions are not exhaustive but may serve as a point of departure to extend and refine the construct and to operationalize ways to assess capacity in communities.

Communicable Disease Control↗

A leptin dose-response study in obese (ob/ob) and lean (+/?) mice.

This experiment determined the amount of leptin required to correct different abnormalities in leptin-deficient ob/ob mice. Baseline food intakes and body weights of lean (+/?) and obese (ob/ob) C57B1/6J mice were recorded for 7 days. An Alzet miniosmotic pump was placed in the peritoneal cavity of each mouse and delivered 0, 1, 2, 5, 10, or 42 microg/day human leptin for 7 days. In ob/ob mice, 2 microg leptin/day reduced food intake and body weight, and increased hypothalamic and brain stem serotonin concentrations. All fat pads were reduced 35-40% by 10 microg leptin/day, and liver weight, lipid, and glycogen decreased. Serum insulin and glucose were reduced in all leptin-treated ob/ob mice, and levels were normalized by 10 microg/day leptin. Low rectal temperatures of ob/ob mice were corrected by 10 and 42 microg/day leptin. These doses also increased brown adipose tissue uncoupling protein expression. The only responses in lean mice were a transient reduction in food intake and weight loss with 10 or 42 microg/day leptin. This study shows enhanced leptin sensitivity in ob/ob mice and suggests that increased temperature and sympathetic activity are indirect responses to high concentrations of protein.

Animals↗

Retention, antimicrobial activity, and clinical outcomes following use of a bioerodible tetracycline gel in moderate-to-deep periodontal pockets.

This randomized, examiner masked, split mouth study evaluated a new model to test periodontal therapy involving a novel bioerodible copolymer gel containing tetracycline hydrochloride. Responses to the tetracycline gel and untreated control were compared for product tolerance and 3 different measures of effectiveness (drug retention, changes in microbial levels, and clinical status). The test gel was administered by syringe into the periodontal pockets of 18 systemically healthy adult volunteers, each of whom presented with 3 or more sites with 6 mm probing depths. Gingival crevicular fluid samples were used to monitor daily drug levels over 7 days, while clinical responses were assessed at day 30. Overall, the test gel was well-tolerated by all patients. For the 3 effectiveness measures, tetracycline was released throughout the observation period and mean levels exceeded 100 microg/mL over 6 days, statistically significant reductions in selected periodontal pathogens were evident at day 7 but not at day 30, and mean probing depth reductions at test sites were 1.12 mm at 30 days versus 0.36 mm at untreated control sites (P=0.012). The safety profile, longer-term drug retention, antimicrobial activity, and clinical response in this Phase I study suggest that this tetracycline-containing copolymer gel platform may represent a safe and effective bioerodible therapy for periodontitis. The experimental model also shows merit for early phase clinical testing of novel therapeutic agents.

Administration, Topical↗