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Biomedical subjects

J R Landis

Publications and source records attributed to J R Landis.

At least 19 recordsLinked to original sources

31P-NMR evaluation of postischemia renal ATP and pH levels after ATP-MgCl2 treatment in rabbits.

Phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy was used to measure adenosine triphosphate (ATP) concentration and pH in vivo in rabbits subjected to a 40-minute period of unilateral renal ischemia to determine the effect of infusing ATP-magnesium chloride (MgCl2, 100 mumol/kg) versus saline at the initiation of reperfusion. Data were compared initially by analysis of variance and then analyzed further using a general linear model with covariate adjustment. ATP-MgCl2-treated animals did not have higher ATP levels during recovery but did have significantly higher renal blood flow (p less than 0.05), a significantly decreased rate of recovery from acidosis (p less than 0.05), and significantly higher urinary output (p less than 0.01) than saline-treated animals during the recovery period. Therefore, treatment with ATP-MgCl2 improves postischemic functional parameters in this model of moderate injury without functioning as a direct source of ATP or its precursors. These data add support to the emerging concept that intracellular acidosis protects cells from reperfusion injury.

Adenosine Triphosphate

Prediction of malignant hyperthermia susceptibility in low-risk subjects. An epidemiologic investigation of caffeine halothane contracture responses. The North American Malignant Hyperthermia Registry.

The most commonly used laboratory test for predicting malignant hyperthermia susceptibility is the caffeine halothane contracture test. However, the specificity and sensitivity of proposed North American diagnostic guidelines for this test have never been evaluated in a large, human study population. Therefore, the authors conducted a multiinstitutional, prospective study of skeletal muscle contracture responses in a subject population at low risk for malignant hyperthermia susceptibility to help determine the specificity of the proposed guidelines. Subjects were selected arbitrarily from a population of patients undergoing surgery unrelated to performance of a diagnostic muscle biopsy. Subjects were admitted to this study and were presumed nonsusceptible if there was no evidence of any of the following malignant hyperthermia risk factors: prior abnormal response to triggering anesthetic agents, myopathy, or family history of malignant hyperthermia susceptibility. The authors suggested rejection of the proposed diagnostic guidelines if an 85% specificity estimate among subjects could not be obtained. The authors analyzed the responses of 1,022 muscle fascicles, derived from 176 subjects, to the following: 1) separate administration of 3% halothane or incremental caffeine concentrations, or 2) the joint administration of 1% halothane and incremental caffeine concentrations. The following contracture results were obtained. First, for individual fascicles, 9.2% exceeded a greater than 0.7 g threshold for 3% halothane, 15.2% exceeded a greater than or equal to 0.2 g threshold for 2 mM caffeine, 32.4% exceeded a 1-g increase for less than 4 mM caffeine, 2.6% had a greater than 7% maximal increase in tension at 2 mM caffeine, and 63.5% had a "halothane caffeine-specific concentration" at less than or equal to 1 mM caffeine. Second, the percentages of subjects with 1 or more fascicles exceeding the proposed threshold were as follows: 45.8% for the four-component, 28.8% for the three-component, and 32.7% for the two-component contracture test. Third, the percentages of subjects with 1 or more fascicles exceeding the proposed threshold for both halothane and caffeine were as follows: 9.5% for 3% halothane and 2 mM caffeine, 2.0% for 3% halothane and 7% maximal increase in tension at 2 mM caffeine, and 11.0% for 1% halothane and 2 mM caffeine. Fourth, center-to-center differences were the major source of variation in the rate that subjects exceeded proposed thresholds. These data demonstrate that proposed diagnostic guidelines must be modified to improve specificity estimates before adoption by diagnostic centers.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Determinants of bone density in young women. I. Relationships among pubertal development, total body bone mass, and total body bone density in premenarchal females.

Bone mass accretion during puberty appears to be critical in the development of peak bone mass, which, in turn, is believed to be a major determinant of osteoporosis risk. Although genetics may be the primary determinant of peak bone mass, modifiable secondary factors, such as nutrition and hormone exposure, may significantly affect bone mass accretion during the second decade of life. As part of a longitudinal study of major determinants of bone development during puberty, we obtained cross-sectional measurements from 112 premenarchal caucasian females (mean +/- SD age, 11.9 +/- 0.49 yr at study entry). Total body bone mineral density (TBBMD) and total body bone mineral content (TBBMC) were measured by dual energy x-ray absorptiometry and compared to anthropometric, pubertal development, urinary steroid and gonadotropin levels, and nutrient intake. An integrated estrogen exposure index was developed and used to evaluate the cumulative effect of circulating estrogen levels on both development. Compared to normative reference data for adults, our subjects possessed 90% of adult height, 68% of adult weight, 83% of adult TBBMD, and 53% of TBBMC. The strongest combined predictors of prepubertal TBBMD and TBBMC were body weight, followed by height and pubertal development. Urinary estradiol levels were positively correlated with dietary intake of iron and vitamin B6.

Adolescent

Elastase as an indicator of periodontal disease progression.

THIS STUDY SOUGHT TO EVALUATE the ability of gingival crevicular fluid (GCF) elastase to predict attachment and bone loss in human periodontitis. Thirty subjects who were medically healthy and had a history of progressive periodontitis were studied with an automated probe. Five sites in each patient were monitored bi-monthly for a 6-month period for attachment loss. Subtraction radiography was utilized at the beginning and end of the study to monitor bone loss. GCF elastase was measured at 0 month and then bi-monthly by collecting GCF on paper strips impregnated with PMN leukocyte elastase substrate inserted into the gingival crevice for 15 seconds. After 8 minutes of reaction time, the strips were scored relative to fluorescent standards in an ultraviolet view box. Strips were then eluted in methanol and total elastase measured by spectrofluorometry. Total elastase was significantly higher in sites demonstrating progressive attachment loss than in inactive sites (2.81 +/- .29 versus 2.03 +/- .07, P less than 0.0005) and sites demonstrating bone loss (2.32 +/- .17 versus 2.01 +/- .08 P less than 0.05). When considering the joint presence of bone loss and attachment loss of 1.0 mm or greater in the 6-month period following a visual elastase kit score of 2 or greater, the test kit shows a sensitivity and specificity of 82% and 66%, respectively. This study demonstrated that GCF elastase levels are significantly higher in sites demonstrating progressive periodontal attachment and bone loss assessed 6 months later and may serve as a predictor of future bone and attachment loss.

Adult

The prevalence of asymptomatic gallstones in the general population.

The gallbladder and biliary system were scanned by real-time ultrasound in 2274 patients undergoing diagnostic ultrasound for other than gallbladder disease. Patients (212) with previous gallbladder symptoms or with nonvisualization of their gallbladder were excluded from the study. Obesity is the most important risk factor for the development of asymptomatic gallstones in women (P less than .01), although it is not a significant factor in men. Increasing age is an important risk factor for both sexes, and the only significant risk factor in men (P less than .01). While few men have asymptomatic gallstones before the age of 40, 5% of women aged 20-29 and 9% aged 30-39 do. In the 40 and over age group, men (14%) and women (11%) had insignificantly different prevalences. In women, the number of previous pregnancies is a significant risk factor (chi-square = 5.4, P = .02). For instance, there is a 3%, 8%, and 17% overall frequency of gallstones in women with 0, 3, and 6 or more previous pregnancies, respectively. A stepwise logistic regression analysis, after adjusting for age, body mass index, and for women, number of pregnancies, found no significant increased risk related to race (P = .40), high blood pressure (P = .43), heart disease (P = .47), or diabetes (P = .46). After age adjustment, there is no significant gender effect (P = .25). Asymptomatic gallstones are a relatively common occurrence in men over 40 and women over 30. While age is the only significant risk factor in men, obesity, parity, and to a lesser extent age were significant risk factors in women.

Adult

Diagnostic radiology peer review: a method inclusive of all interpreters of radiographic examinations regardless of specialty.

A proposed method of assessing the quality of diagnostic radiographic examinations includes peer review designed to evaluate physicians, including nonradiologists, involved in the performance and interpretation of such examinations. A pilot project evaluated this system with randomly selected Pennsylvania Blue Shield data files of 10 providers billing for chest radiography interpretations during the second quarter of 1989. Of the 98 chest radiographs reviewed blindly, all inadequately marked radiographs and incomplete written reports were produced by nonradiologists. Technical quality of images obtained by radiologists did not significantly differ from that of images obtained by nonradiologists (P = .189). All five interpretive errors that could have seriously affected the patient's health care were produced by nonradiologists (P = .019). Four of these serious errors were made by providers billing for fewer than 25 radiographs. While administrative and time cost limitations are obvious, this method of peer review encompasses all physicians billing for a particular radiographic service, irrespective of specialty.

Blue Cross Blue Shield Insurance Plans

Generalized variance component models for clustered categorical response variables.

A generalized variance component model is proposed for the analysis of a categorical response variable with extra-multinomial variation. Categorical data obtained from research designs such as randomized multicenter clinical trials or complex sample surveys with clustering frequently exhibit extra-variation resulting from intracluster correlation. General correlation patterns are accounted for by utilizing a mixed-effects modelling approach, estimating the cluster variance components through the method of moments and modelling functions of the observed proportions through the use of estimating equations. A flexible set of assumptions characterizing the underlying covariance structure for the proportions can be accommodated. The importance of accounting for extra-variation when performing hypothesis tests is highlighted with an application to data from a multi-investigator clinical trial.

Analysis of Variance

Effect of empiric antiarrhythmic therapy in resuscitated out-of-hospital cardiac arrest victims with coronary artery disease.

The effect of empiric antiarrhythmic therapy with quinidine and procainamide on long-term mortality was examined in 209 patients with coronary artery disease resuscitated after out-of-hospital cardiac arrest. The antiarrhythmic agent used was determined by the patient's private physician without knowledge of the study ambulatory electrocardiogram. Of the 209 patients, procainamide was prescribed in 45 (22%), quinidine in 48 (23%) and no antiarrhythmic therapy in 116 (55%). Digoxin therapy was initiated in 101 patients. The 2-year total survival rate for the quinidine, procainamide and nontreated patients was 61, 57 and 71% (p less than 0.05), and for sudden death was 69, 69 and 89% (p less than 0.01), respectively. These observations suggest that empiric antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest did not affect total mortality and was associated with an increased frequency of sudden death.

Aged

Efficacy of automated biopsy guns versus conventional biopsy needles in the pygmy pig.

Debate over which biopsy needle is the best has intensified recently with the introduction of automated biopsy guns including the 18-gauge long-throw and short-throw Biopty, the 18-gauge Cook, and the 14- and 18-gauge Klear Kut. To evaluate the efficacy of these mechanized biopsy guns versus that of conventional manual biopsy needles in the acquisition of adequate tissue for histopathologic evaluation, open hepatic and renal biopsies were performed in 15 pygmy pigs. The specimens were evaluated separately in a double-blind fashion by two histopathologists using graded criteria. Overall, the best results were obtained with the manual 14-gauge Tru-Cut needle, the long-throw 18-gauge Biopty gun, and the 18-gauge Cook biopsy gun. By comparison, the aspiration-type needles did not perform as well when considered as a group. Several other needles scored well in the biopsy of either the liver or kidney, but not in both. Disappointing results were obtained with the Klear Kut guns (both 14- and 18-gauge) and the Vacu Cut and PercuCut needles.

Animals

Alterations in adipocyte adenylate cyclase activity in morbidly obese and formerly morbidly obese humans.

Studies examining animal models of genetic obesity have identified defects in adipocyte hormone-stimulated lipolysis that involve the adenylate cyclase transmembrane signaling system, specifically those components that decrease adenylate cyclase activity. To determine whether obese people demonstrate alterations in adenylate cyclase activity that could contribute to the maintenance of obesity by inhibiting lipolysis, we examined human adipocytes from patients who were lean, obese, or formerly obese. Fat samples were obtained from the lower abdomen of 14 women who were morbidly obese (obese group), from 10 women who were formerly morbidly obese and had lost weight after gastric stapling (postobese group), and from 10 similarly aged women of normal weight (controls). Adipocyte adenylate cyclase activity was determined under ligand-free (no stimulatory or inhibitory influences present), hormone-stimulated (isoproterenol, 10(-6) mmol/L), and maximal (cells stimulated with 10 mumol/L forskolin) conditions by measuring cyclic adenosine monophosphate (cAMP) levels by radioimmunoassay. The activity of adenylate cyclase was significantly different (p less than 0.01) in the three groups. Adipocytes from obese women had lower levels of cyclase activity under both ligand-free (5% vs 16% of maximal) and hormone-stimulated conditions (76% vs 100% of maximal) than adipocytes from normal women. Postobese women had levels of hormone-stimulated cAMP identical to those of normal women but still had abnormal ligand-free levels (under 5%). These results suggest the presence of an alteration in adipocyte adenylate cyclase regulation in morbidly obese women that is not entirely corrected when weight is lost after food intake is reduced by gastric stapling. This alteration in ligand-free cAMP activity may contribute to the development and maintenance of obesity.

Adenylyl Cyclases

Lipoprotein lipids in women with androgen excess: independent associations with increased insulin and androgen.

Concentrations of triglycerides are increased and concentrations of high-density lipoprotein (HDL) cholesterol are low in women with hyperandrogenism. These alterations could be related to excessive androgen or estrogen, to hyperinsulinism, or to a combination of these abnormalities. We examined their independent influences on lipids in 21 women with hyperandrogenism, subgrouped according to apparent source of androgen excess. Results for lipid, androgen, and insulin did not differ among subgroups, so these data were pooled. Free plus albumin-bound testosterone (uT) was correlated with triglycerides (r = 0.69, P less than 0.01) and HDL cholesterol (r = -0.56, P less than 0.01). Both triglycerides (r = 0.66, P less than 0.01) and HDL cholesterol (r = -0.48, P less than 0.05) were also correlated with insulin measured during fasting. Partial correlation revealed that, after adjusting for insulin, lipids were associated with uT. This suggests that androgen excess is independently related to lipid excess. Insulin also was correlated with lipids when adjusted for uT. Free plus albumin-bound estradiol was not associated with any of the lipids. We conclude that altered lipids in women with hyperandrogenism result from the independent effects of androgen and insulin.

Adult

Origins of cerebral palsy.

Analyses were undertaken to determine the causes of cerebral palsy in a prospective study of 43,437 full-term children. Presumed causes were found for about 71% of the 34 quadriplegic and 40% of the 116 nonquadriplegic patients with cerebral palsy. Risk estimates based on predictive models, adjusted for multiple factors, suggest that 53% of the quadriplegic patients with cerebral palsy could be attributed to congenital disorders, 14% to birth asphyxia, and 8% to other identified disorders. Thirty-five percent of the nonquadriplegic patients with cerebral palsy could be attributed to congenital disorders and 6% to other disorders. In the victims of cerebral palsy, characteristic consequences of birth asphyxia were more often the result of nonasphyxial disorders. These included meconium in the amniotic fluid, low 10-minute Apgar scores, neonatal apnea spells, seizures, persisting neurologic abnormalities, and slow head growth after birth.

Aged

A log-linear model for ordinal data to characterize differential change among treatments.

We propose a family of log-linear models for ordinal data that contain parameters reflecting change patterns to compare treatments relative to change from baseline. Under the most general model, rates of change can depend not only upon the direction of change, but also upon the level of the baseline classification. We describe methods for selection of a parsimonious model and for tests of hypotheses concerning treatment differences. Interpretation of treatment differences in the follow-up response profiles, within baseline strata, employs the concept of stochastic ordering. Data from two clinical trials illustrate the proposed procedure.

Analysis of Variance

Summary attributable risk estimation from unmatched case-control data.

We propose an alternative method to obtain summary estimators, variances and confidence intervals for attributable risk measures. This method combines weighted exposure prevalences for cases and controls across strata formed by the cross-classification of relevant covariates to form estimates of attributable risk among the exposed and attributable risk in the target population. The major benefit of this approach over those previously proposed in the literature is that it operates on data summed across strata rather than on estimation of statistics within each stratum. This alternative method for attributable risk measures utilizes the Mantel-Haenszel estimate of an average odds ratio, and can be implemented using the matrix procedure in SAS. This method is appropriate even when the within-stratum sample sizes are too small for other methods to be valid. Simulation results indicate that this method is superior to others with respect to bias and coverage probability for confidence intervals.

Alcohol Drinking

Secular trends in body mass index and skinfold thickness with socioeconomic factors in young adult women.

Secular trends in the relationship of body mass index (BMI) and skinfold thickness to educational and income levels were examined for white and black women aged 18-34 y over the period 1960-80 with data from three successive national surveys: NHES Cycle I, NHANES I, and NHANES II. Statistical models were fitted to assess the variability in mean BMI over time within levels of education or income. Mean BMI and skinfold thickness were negatively associated with both education and income. Over the 20-y period mean BMI increased for both white and black women at all levels of income and education. Because the increase in mean BMI was greater at lower educational levels, the differentiation of BMI by educational level increased over time, yielding a stronger negative association. In contrast differentiation of BMI by income category decreased over time. Black-white differences in mean BMI at comparable educational and income levels persisted over this period.

Adult

Secular trends in body mass index and skinfold thickness with socioeconomic factors in young adult men.

Secular trends in the relationship of body mass index (BMI) and skinfold thickness to educational and income levels were examined for white and black men aged 18-34 y over the period 1960-80 with data from three successive national surveys: NHES Cycle I, NHANES I, and NHANES II. Statistical models were fitted to assess the variability in mean BMI over time within levels of education or income. There were few secular changes in mean BMI. In both white and black men a secular change from a slight positive association between mean BMI and education to a negative association was characterized chiefly by an increase in mean BMI at the lowest educational level. A slight positive association between income level and mean BMI persisted almost unchanged over this period. Mean BMI was similar for black and white men. These findings are compared and contrasted with those from a similar study for young women.

Adult

Secular trends in body mass in the United States, 1960-1980.

Data from four National Health Examination Surveys conducted of the US population from 1960 to 1980 were analyzed to determine secular trends in obesity for white and for black adolescents and young adults of both sexes. Body mass index was categorized into four levels using cut points determined by the 50th, 75th, and 85th percentiles at the first survey in 1960-1962. The weighted proportions of persons in these body mass categories were determined, and statistical models were developed to describe secular trend and race effects. No consistent secular trends were found for white or black youths aged 12-17 years. No significant secular trends in obesity were found for white or black young males aged 18-34 years. Both for white and for black adult females, there were significant secular increases in the proportion of adult females in each of the successively heavier categories of body mass index. These increases were identical for white and for black adult females on the log-odds scale, but black adult females were already significantly heavier at the first survey. This race effect persisted throughout the entire time interval.

Adolescent

Predictive value of ventricular arrhythmias in resuscitated out-of-hospital cardiac arrest victims.

Twenty-four hour ambulatory electrocardiograms recorded in 103 survivors of out-of-hospital cardiac arrest were analyzed to find those characteristics of the ventricular premature complex (VPC) which provide the best combination of sensitivity, specificity, and predictive accuracy for subsequent mortality. VPC characteristics were grouped as: (1) frequent (greater than or equal to 25 h-1), (2)bigeminal, (3) multiform, (4) early coupled, (5) pairing, (6) repetitive greater than or equal to 2, (7) repetitive greater than or equal to 3, (8) repetitive greater than or equal to 6, (9) the combination of frequent and repetitive, or (10) complex defined as any multiform, early, bigeminal or repetitive VPC. In an average follow-up period of 43 months, 42 deaths occurred, 17 of which were classified as sudden. Each characteristic was a significant predictor for all causes of subsequent death except early coupled VPCs and repetitive VPCs greater than 6. None of the characteristics reached significance as predictors for sudden death. The number of repetitive VPCs when stratified to none, greater than or equal to 2 and greater than or equal to 3 successive VPCs correlated with mortality in an incremental fashion. The combination of frequent VPCs and repetitive VPCs provided the best combination of sensitivity, specificity and predictive accuracy for death from all causes within five years.

Arrhythmias, Cardiac