Biomedical subjects

S Hunsberger

Publications and source records attributed to S Hunsberger.

At least 19 recordsLinked to original sources

PubMed2001

Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex.

The true prevalence of pulmonary lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex (TSC) is unknown. The prevalence of LAM, radiological features, and lung function in patients with TSC was measured. The presence of LAM, as defined by the presence of cysts by high-resolution chest computed tomography (HRCT) scan, was determined in patients with TSC without prior pulmonary disease (Group 1). To determine the significance of early detection, severity of disease in screened patients (Group 1) was compared with that in patients with TSC with a prior diagnosis of LAM (Group 2). Forty-eight patients with TSC and no prior history of LAM were screened. Of the 38 females, 13 (34%) had LAM; LAM was absent in males. Lung function was preserved in patients with TSC who were found to have LAM by screening. In patients previously known to have LAM, FEV(1) and DL(CO) correlated inversely with severity of disease as assessed by CT scan. The prevalence of LAM in women with TSC was 34%, approximately 10-fold that previously reported, consistent with a large hitherto unrecognized subclinical population of patients at risk for pulmonary complications.

Adult↗

PubMed2001

Imputation strategies for missing data in a school-based multi-centre study: the Pathways study.

Pathways is a multi-centre school-based trial sponsored by the National Heart, Lung, and Blood Institute testing the efficacy of an obesity prevention intervention in American Indian children. During the study's protocol development, we prepared an analysis plan that accounted for missing data. In this paper, we present a case study of the process we used to decide upon the final analysis plan. The primary endpoint of the Pathways study is a comparison of per cent body fat between treatment and usual care groups at the end of a three-year intervention. Other studies on children and Native Americans have had moderate to large amounts of missing data. As a result we were concerned that missing data in Pathways would affect the type I error rate and power of the test of our primary endpoint. We present results from our evaluation of three alternative procedures in this paper. The first is a multiple imputation procedure in which we replace missing values with resampled values from the observed data. The second is based on the Wilcoxon rank sum test; missing data in the intervention group receive the worst ranks. In the third, we use a multiple imputation procedure and replace missing values with predicted values from a regression equation with the coefficients estimated from observed follow-up data and baseline values. We found that the multiple imputation procedure that replaces missing values with predicted values had the best properties of the procedures we considered. The results from our simulation study showed that, for missing data patterns that are relevant to the Pathways study, this procedure has high power and maintains the type I error rate. Published in 2001 by John Wiley & Sons, Ltd.

Analysis of Variance↗

PubMed2001

Testing for treatment and interaction effects in semi-parametric analysis of covariance.

Semi-parametric regression models assume that the effects of covariates on the mean response are additive. We propose a test of additivity when there is one continuous covariate and a group indicator. At p fixed points, the differences of the within-group kernel estimates of the means are calculated, and the likelihood ratio test that the p differences have a constant mean is formed. The kernel bandwidth and the location of the p fixed points are chosen to give the test good power. Performance of the proposed test is compared with parametric and non-parametric tests of additivity. Published in 2001 by John Wiley & Sons, Ltd.

Blood Pressure↗

PubMed2000

Estimation of body fat from anthropometry and bioelectrical impedance in Native American children.

OBJECTIVE: Obesity, as measured by body mass index, is highly prevalent in Native American children, yet there are no valid equations to estimate total body fatness for this population. This study was designed to develop equations to estimate percentage body fat from anthropometry and bioelectrical impedance as a critical part of Pathways, a multi-site study of primary prevention of obesity in Native American children. DESIGN: Percentage fat was estimated from deuterium oxide dilution in 98 Native American children (Pima/Maricopa, Tohono O'odham and White Mountain Apache tribes) between 8 and 11 y of age. The mean fat content (38.4%+/-8. 1%) was calculated assuming the water content of the fat-free body was 76%. Initial independent variables were height, weight, waist circumference, six skinfolds and whole-body resistance and reactance from bioelectrical impedance (BIA). RESULTS: Using all-possible-subsets regressions with the Mallows C (p) criterion, and with age and sex included in each regression model, waist circumference, calf and biceps skinfolds contributed least to the multiple regression analysis. The combination of weight, two skinfolds (any two out of the four best: triceps, suprailiac, subscapular and abdomen) and bioelectrical impedance variables provided excellent predictability. Equations without BIA variables yielded r2 almost as high as those with BIA variables. The recommended equation predicts percentage fat with a root mean square error=3.2% fat and an adjusted r2=0.840. CONCLUSION: The combination of anthropometry and BIA variables can be used to estimate total body fat in field studies of Native American children. The derived equation yields considerably higher percentage fat values than other skinfold equations in children.

Adipose Tissue↗

PubMed2000

Incidence, predictive factors, and prognostic significance of supraventricular tachyarrhythmias in congestive heart failure.

BACKGROUND: The incidence, predictive factors, morbidity, and mortality associated with the development of supraventricular tachyarrhythmias (SVTs) in patients with congestive heart failure (CHF) are poorly defined. METHODS: In the Digitalis Investigation Group trial, patients with CHF who were in sinus rhythm were randomly assigned to digoxin (n = 3,889) or placebo (n = 3,899) and followed up for a mean of 37 months. Baseline factors that predicted the occurrence of SVT and the effects of SVT on total mortality, stroke, and hospitalization for worsening CHF were determined. RESULTS: Eight hundred sixty-six patients (11.1%) had SVT during the study period. Older age (odds ratio [OR], 1.029 for each year increase in age; p = 0.0001), male sex (OR, 1.270; p = 0.0075), increasing duration of CHF (OR, 1.003 for each month increase in duration of CHF; p = 0.0021), and a cardiothoracic ratio of > 0.50 (OR, 1.403; p = 0.0001) predicted an increased risk of experiencing SVT. Left ventricular ejection fraction, New York Heart Association functional class, and treatment with digoxin vs placebo were not related to the occurrence of SVT. After adjustment for other risk factors, development of SVT predicted a greater risk of subsequent total mortality (risk ratio [RR] = 2.451; p = 0.0001), stroke (RR = 2.352; p = 0.0001), and hospitalization for worsening CHF (RR = 3. 004; p = 0.0001). CONCLUSION: In CHF patients in sinus rhythm, older age, male sex, longer duration of CHF, and increased cardiothoracic ratio predict an increased risk for experiencing SVT. Development of SVT is a strong independent predictor of mortality, stroke, and hospitalization for CHF in this population. Prevention of SVT may prolong survival and reduce morbidity in CHF patients.

Age Factors↗

PubMed1999

Behavioral and pharmacologic interventions: the Raynaud's Treatment Study.

The Raynaud's Treatment Study (RTS) exemplified clinical trials with treatments that differ qualitatively both in their modes and in their methods of delivery. The RTS compared finger-temperature biofeedback to slow-release nifedipine, a calcium channel blocker, in patients with primary Raynaud's disease. Factors influencing the study design were the nature of the interventions and control measures of the protocol, the possibility of perceived differences by the patients between the treatments once the final protocol was developed, and concern on the part of the investigators over the fact that the primary endpoint was self-reported. This paper presents the final statistical model: a double parallel design with both a placebo group and a nonspecific behavioral control group.

Biofeedback, Psychology↗

PubMed1999

Design and statistical analysis for the Pathways study.

We report the design, rationale, and statistical procedures used in Pathways, a randomized, school-based intervention for the primary prevention of obesity in American Indian children. The intervention, which is now being implemented in 7 American Indian communities around the country, includes a health-promotion curriculum, a physical education program, a school meal program, and a family involvement component. Forty-one schools serving American Indian children were randomly assigned to be either intervention or control groups. The intervention will begin in the third grade and continue through the end of the fifth grade. Efficacy of intervention will be assessed by differences in mean percentage body fat, calculated by a prediction equation, between intervention and control schools at the end of the fifth grade. Power computations indicate that the study has power to detect a mean difference of 2.8% in body fat. Data analysis will use intention-to-treat concepts and the mixed linear model. The study will be completed in 2000.

Analysis of Variance↗

PubMed1999

Body composition assessment in American Indian children.

Although the high prevalence of obesity in American Indian children was documented in several surveys that used body mass index (BMI, in kg/m2) as the measure, there is limited information on more direct measurements of body adiposity in this population. The present study evaluated body composition in 81 boys (aged 11.2+/-0.6 y) and 75 girls (aged 11.0+/-0.4 y) attending public schools in 6 American Indian communities: White Mountain Apache, Pima, and Tohono O'Odham in Arizona; Oglala Lakota and Sicangu Lakota in South Dakota; and Navajo in New Mexico and Arizona. These communities were participating in the feasibility phase of Pathways, a multicenter intervention for the primary prevention of obesity. Body composition was estimated by using a combination of skinfold thickness and bioelectrical impedance measurements, with a prediction equation validated previously in this same population. The mean BMI was 20.4+/-4.2 for boys and 21.1+/-5.0 for girls. The sum of the triceps plus subscapular skinfold thicknesses averaged 28.6+/-7.0 mm in boys and 34.0+/-8.0 mm in girls. Mean percentage body fat was 35.6+/-6.9 in boys and 38.8+/-8.5 in girls. The results from this study confirmed the high prevalence of excess body fatness in school-age American Indian children and permitted the development of procedures, training, and quality control for measurement of the main outcome variable in the full-scale Pathways study.

Adipose Tissue↗

PubMed1999

Physical activity assessment in American Indian schoolchildren in the Pathways study.

The objective of the Pathways physical activity feasibility study was to develop methods for comparing type and amount of activity between intervention and control schools participating in a school-based obesity prevention program. Two methods proved feasible: 1) a specially designed 24-h physical activity recall questionnaire for assessing the frequency and type of activities and 2) use of a triaxial accelerometer for assessing amount of activity. Results from pilot studies supporting the use of these methods are described. Analyses of activity during different segments of the day showed that children were most active after school. The activities reported most frequently (e.g., basketball and mixed walking and running) were also the ones found to be most popular in the study population on the basis of formative assessment surveys. Both the physical activity recall questionnaire and the triaxial accelerometer methods will be used to assess the effects of the full-scale intervention on physical activity.

Asian People↗

PubMed1997

Effects of diet and sexual maturation on low-density lipoprotein cholesterol during puberty: the Dietary Intervention Study in Children (DISC).

BACKGROUND: The Dietary Intervention Study in Children (DISC) is a multicenter, randomized, controlled clinical trial designed to examine the efficacy and safety of a dietary intervention to reduce serum LDL cholesterol (LDL-C) in children with elevated LDL-C. METHODS AND RESULTS: The effects of dietary intake of fat and cholesterol and of sexual maturation and body mass index (BMI) on LDL-C were examined in a 3-year longitudinal study of 663 boys and girls (age 8 to 10 years at baseline) with elevated LDL-C levels. Multiple linear regression was used to predict LDL-C at 3 years. For boys, LDL-C decreased by 0.018 mmol/L for each 10 mg/4.2 MJ decrease in dietary cholesterol (P<.05). For girls, no single nutrient was significant in the model, but a treatment group effect was evident (P<.05). In both sexes, BMI at 3 years and LDL-C at baseline were significant and positive predictors of LDL-C levels. In boys, the average LDL-C level was 0.603 mmol/L lower at Tanner stage 4+ than at Tanner stage 1 (P<.01). In girls, the average LDL-C level was 0.274 mmol/L lower at Tanner stage 4+ than at Tanner stage 1 (P<.05). CONCLUSIONS: In pubertal children, sexual maturation, BMI, dietary intervention (in girls), and dietary cholesterol (in boys) were significant in determining LDL-C. Sexual maturation was the factor associated with the greatest difference in LDL-C. Clinicians screening for dyslipidemia or following dyslipidemic children should be aware of the powerful effects of pubertal change on measurements of lipoproteins.

Body Mass Index↗

PubMed1997

Do children eat what they say? Validity of intended food choices among Native American school children.

OBJECTIVE: To examine the agreement between school children's intended food choices and observed food choices. DESIGN: Native American students in the second through fifth grade completed a questionnaire that asked them to select from 10 paired food choices for a given meal or snack. Three weeks later students chose among foods identical to those on the questionnaire as part of their usual school lunch or breakfast over three consecutive days; afternoon snacks were also offered. RESULTS: Agreement between students' intended food choices and observed food choices was examined across 10 food pairs. The composite kappa coefficient between intended and observed food choices was 0.09 (95% confidence interval 0.06, 0.012), including virtually no agreement above that expected by chance. There were no differences in agreement by sex or grade. CONCLUSIONS: Intended food choices were not significantly associated with observed food choices. It is unclear whether intended food choices reflect nutrition knowledge, socially desirable responses, food preferences, or some other dimension of eating behavior. Although responsive to school-based nutrition interventions, the interpretation of changes in intended food choices must be clarified in future research.

Child↗

PubMed1996

Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury.

BACKGROUND: We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for > or = 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell-specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo. METHODS AND RESULTS: Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n = 9), VEGF 0.72 mg (n = 9), or saline (n = 10) as a daily left atrial bolus (days 10 to 16). Additional dogs were randomized to VEGF 0.72 mg (n = 6) or saline (n = 5); however, treatment was delayed by 1 week. Coincident with the institution of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased maximal collateral flow but did not exacerbate neointimal accumulation. VEGF had no discernible effect on maximal collateral flow, but it exacerbated neointimal thickening after vascular injury. CONCLUSIONS: Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation at sites of vascular injury. Although VEGF did not increase collateral development as administered in this study, it significantly exacerbated neointimal accumulation. These data provide support for the clinical investigation of bFGF in selected patients with ischemic heart disease.

Animals↗

PubMed1995

Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart.

BACKGROUND: Recently we reported that intracoronary administration of basic fibroblast growth factor (bFGF), a potent angiogenic peptide, increases collateral blood flow in dogs subjected to progressive left circumflex coronary artery (LCx) occlusion. The aim of the present study was to examine the effect of systemically administered bFGF on collateral blood flow and to assess its pharmacokinetics and potential side effects. METHODS AND RESULTS: Forty-seven dogs were subjected to progressive ameroid-induced occlusion of the LCx, an intervention known to induce the development of collateral vessels. In phase I of the investigation, dogs were randomized to receive bFGF 1.74 mg/d (n = 10) or saline (n = 9) as a left atrial injection for 4 weeks. Relative collateral blood flow was assessed serially with radiolabeled microspheres in the conscious state during maximal coronary vasodilatation. Initiation of bFGF treatment was temporally associated with a marked acceleration of collateral development; however, collateral flow in control dogs improved toward the end of the study, approaching that of bFGF-treated dogs at the 38-day end point. Phase II of the investigation was a three-armed study of extended duration to determine whether bFGF caused a sustained increase in collateral function. Dogs were randomized to receive bFGF 1.74 mg/d for 9 weeks (n = 7), bFGF 1.74 mg/d for 5 weeks followed by placebo for 4 weeks (n = 11), or placebo for 9 weeks (n = 10). Relative and absolute collateral blood flow were assessed serially with microspheres during maximal coronary vasodilatation. Between the 10th and 17th days after ameroid placement, bFGF-treated dogs exhibited marked improvement in collateral flow such that maximal collateral conductance exceeded that of controls by 24% at the 5-week crossover point. Final collateral conductance was similar in dogs receiving bFGF for 5 and 9 weeks despite withdrawal of treatment in the former group. bFGF administration was associated with a 21% increase in final collateral conductance as well as a 49% increase in collateral zone vascular density. Prolonged bFGF administration was also associated with a decrease in arterial pressure, moderate thrombocytopenia, and moderate, reversible anemia. CONCLUSIONS: Systemic administration of bFGF enhanced collateral conductance in dogs with progressive single-vessel coronary occlusion. The beneficial effect of bFGF occurred primarily between the 7th and 14th days of therapy, and regression of collateral development was not noted after withdrawal of treatment. The present investigation provides impetus to the concept that collateral development can be enhanced pharmacologically-specifically by bFGF-raising the possibility that such an intervention might eventually be applied clinically.

Animals↗

PubMed1992

Pharmacokinetics of ANF and urodilatin during cANF receptor blockade and neutral endopeptidase inhibition.

Urodilatin is a new member of the family of natriuretic peptides. It is of renal origin. Previous reports indicate that urodilatin is natriuretic in lower doses than atrial natriuretic factor (ANF)-(99-126) and that it might be more effective than ANF in the treatment of cardiovascular edema. The present study was designed to compare the pharmacokinetics of the hydrolysis and clearance of 125I-labeled urodilatin and 125I-ANF. In control rats, the volume of distribution (Vss), metabolic clearance rate (MCR), and distribution half-life (distribution t1/2) of urodilatin in plasma were not significantly different from those of ANF. Infusion of clearance (c)ANF-(4-23), a specific ligand for receptors that clear ANF in excess amounts (i.e., a bolus injection of 100 micrograms/kg followed by a continuous infusion of 10 micrograms.kg-1 x min-1), increased the amount of intact peptide in the plasma to the same extent for both urodilatin and ANF. In addition, cANF-(4-23) decreased the Vss and the MCR and increased the distribution t1/2 of both peptides to about the same degree. Prior treatment of rats with SQ-28,603, a specific neutral endopeptidase (NEP; EN 3.4.24.11) inhibitor, was without significant effect on the metabolic clearance of urodilatin, whereas it decreased the clearance of ANF by 65%. Furthermore, an infusion of SQ-28,603 suppressed the appearance of the hydrolytic products of ANF in blood but not of urodilatin. Moreover, the inhibitor increased the total amount of ANF recovered in the kidneys to five times the control values, whereas it did not alter the renal uptake of urodilatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

PubMed1990

Clinical predictors of infection of central venous catheters used for total parenteral nutrition.

To identify predictors of infection in catheters used for total parenteral nutrition (TPN), clinical and microbiological data were prospectively collected on 169 catheter systems (88 patients). Based on semiquantitative catheter cultures, infection was associated with a positive insertion site skin culture taken close to the time of catheter removal (relative risk [RR] = 4.50), especially one yielding greater than or equal to 50 colonies of an organism other than coagulase-negative staphylococci. Infection was also associated with erythema at the insertion site greater than 4 mm in diameter (RR = 2.93). In a subset of 67 catheters for which blood cultures were obtained, infection was also associated with a positive peripheral venous blood culture (RR = 5.90) and a positive central venous blood culture obtained through the catheter (RR = 5.44). Based on a logistic regression model, periodic cultures of the insertion site should be useful in evaluating subsequent fever in stable patients with indwelling central venous catheters. Another source of fever is likely if inflammation is absent and there is either no colonization or there is colonization by less than 50 colonies of coagulase-negative staphylococci at the insertion site. Conversely, the catheter should be removed and cultured semiquantitatively if the site is colonized by an organism other than coagulase-negative staphylococci. We suggest that blood culture results add little to the risk estimate in these situations.

Adult↗

PubMed1989

A physiologically based model of 1-nitropyrene metabolism after inhalation or ingestion.

The nitrogen-containing polycyclic aromatic hydrocarbon 1-nitropyrene (NP), a bacterial mutagen and mammalian carcinogen, is a ubiquitous environmental pollutant. A physiologically based toxicokinetic model was developed describing the disposition of NP after oral administration (ingestion) or after inhalation. The model incorporated the following compartments: blood, upper respiratory tract, lung, liver, kidney, gastrointestinal (GI) tract, and a general tissue compartment. First-order rate constants for absorption of NP from the GI tract (2 h-1), metabolism by the liver (30 h-1), excretion of metabolites in bile and urine (2 and 4 h-1, respectively), and covalent binding of NP metabolites to tissue macromolecules (0.05, 0.05, 0.1, and 0.001 h-1 for lung, liver, kidney, and general tissue compartment, respectively) determined from model simulations were used to describe absorption, biotransformation, and excretion of NP. Physiological parameters such as alveolar ventilation, cardiac output, blood flow to organs volume, and tissue/blood partition coefficients described movement of NP and metabolites among compartments. Model predictions for concentrations of NP and metabolites in tissues were compared to experimentally determined data obtained in rats after inhalation of NP. Model predictions for concentrations of NP metabolites covalently bound to tissue macromolecules agreed with experimentally determined data in rats. Levels of bound material in lung and liver were about one-tenth that found in kidney. Results indicated that NP movement among tissue compartments could be described to a large extent by blood flow and organ volume alone (e.g., tissue/blood partition coefficients = 1). The use of physiologically realistic parameters will enable scaling of the model developed using animal studies to predict disposition of NP in humans.

Administration, Inhalation↗

PubMed1988

Lung, liver, and kidney as potential target organs after exposure to 1-nitropyrene, as determined by the time course of covalently bound material.

Previous studies in which rats were exposed to [14C]-1-nitropyrene by inhalation indicated that lung, liver, and kidney consistently accumulated the highest concentrations of 14C after exposure. The purpose of the study described here was to determine the extent to which this 14C was covalently bound to macromolecules. Male F344/N rats were exposed to 360 ng [14C]-1-nitropyrene/l air for 1 h resulting in an average of 2.2 micrograms 1-nitropyrene deposited per rat. An additional group of rats was given 4.2 micrograms [14C]-1-nitropyrene by gavage. Total 14C in 23 tissues was determined for up to 96 h after inhalation exposure and up to 30 d after gavage. Lung, liver, and kidney contained the highest concentrations of 14C. Samples of these tissues were exhaustively extracted to determine the amount of radioactivity covalently bound to macromolecules. Regardless of the route of administration, the kidneys had the highest concentrations of covalently bound 14C. At 96 h after exposure kidneys had overall mean concentrations of 2.7 pmol bound/g tissue.micrograms nitropyrene administered. The overall mean concentration in liver was 0.18 pmol bound/g.microgram and the overall mean concentration in lung was 0.06 pmol/g.microgram at 96 h after exposure. Covalently bound material persisted in kidneys for the duration of the study (30 d postexposure). The calculated half-time for removal of bound 14C from kidneys was 150 d. These data suggest that kidney should be considered as one of the organs at risk after exposure to nitropyrene by inhalation or ingestion.

Administration, Inhalation↗

PubMedDate not supplied

Testing for differences in changes in the presence of censoring: parametric and non-parametric methods.

Some commonly used parametric and non-parametric methods for analysing repeated measures with incomplete observations are briefly reviewed. The performances of these methods in the presence of completely random, as well as informative censoring are compared in simulated experiments generated under the linear random effects model with parameter values derived from realistic examples. The effects of some moderate model deviations are also compared. The results indicate that in the presence of informative censoring, the usual parametric and nonparametric methods derived under the assumption of random censoring could either suffer severe loss of power or provide false positive results. The conditional linear model for informative censoring when used in conjunction with the bootstrap variance estimation procedure performed well under both random and informative censoring mechanisms. The non-parametric procedure obtained by ranking the individual summary statistics, although not as efficient as the conditional linear model with robust variance, also performed relatively well in most situations. Therefore, in situations in which informative censoring is likely to occur it is important to select the proper method of analysis to test for the informativeness of censoring and to account for its effects.

Bias↗