Search PubMed⌕ Search

Biomedical subjects

R J McCarter

Publications and source records attributed to R J McCarter.

At least 73 records · Page 4Linked to original sources

Transient reduction of metabolic rate by food restriction.

It is widely held that restriction of food intake leads to a decrease in metabolic rate, and this effect has been implicated as the mechanism by which food restriction retards aging in laboratory rodents. Data on which this belief is based were obtained mostly from studies of basal metabolic rate after acute rather than chronic food restriction. In contrast we previously reported no effect of chronic food restriction on metabolic rate measured under usual living conditions. The present study examines changes in metabolic rate immediately after restriction of food so as to include the initial response to decreased intake of food. Two groups of specific pathogen-free Fischer 344 rats were housed under barrier conditions from 6 to 24 wk of age. Restricted rats were fed 60% of food consumed by rats eating ad libitum. Metabolic rate was measured indirectly by gas analysis with rats under normal daily living conditions (24MR) and basal metabolic rate (BMR) was also measured. Both 24MR and BMR decreased after food restriction, but this decrease was transient, so that within a few weeks metabolic rate of restricted rats was the same as that of rats fed ad libitum.

Aging↗

Metabolic effects of aminophylline in rats.

Whole body metabolic rate is elevated after administration of methylxanthines, but the mechanism by which this occurs is not clear. We have investigated the hypothesis that this increase in metabolic rate is in part due to increased physical activity. Metabolic rate and spontaneous cage activity of Fischer 344 rats were measured over a 24-h period before and during aminophylline treatment. Weight, food, and water consumption were also measured. Our results show an increase in metabolic rate with a simultaneous increase in spontaneous activity over the 24-h period. These results are consistent with the hypothesis that increased physical activity is in part responsible for the increase in cellular metabolism that follows administration of aminophylline.

Aminophylline↗

Integrated Academic Information Management Systems (IAIMS). Part II. Planning and implementing integrated information services. The management of change: lessons learned from the IAIMS experience.

The critical elements of the change process were designed into the strategic planning process and the pilot project for the Integrated Academic Information Management System (IAIMS) at the University of Maryland. These elements were: Support by the institutional leadership; a critical mass of interested participants from diverse groups across the organization, committed to the project and with ownership of the plan; a motivating level of dissatisfaction with the status quo; the construction of a scenario describing the desired future and an assessment of needs to achieve it; technical and consulting help; a pilot project with replicable features to demonstrate the concept and feasibility of the approach; and participation of opinion leaders initially with later identification of additional opinion leaders who would become part of the pattern of acceptance of the innovation and diffusion of the technology across the campus.

Academic Medical Centers↗

Familial risks of congenital heart defect assessed in a population-based epidemiologic study.

Congenital heart defects (CHD) represent a heterogeneous group of disorders caused by chromosome abnormalities, mendelian disorders, teratogenic exposures, and unknown etiologic mechanisms. A large group of various isolated defects is presumably multifactorial in origin. Previous studies of familial risks for specific anatomic defects obtained from clinical series may include significant biases and obscured pathogenic relationships. In this population-based study we analyzed all cases of CHD in infants and a control birth cohort in the Baltimore-Washington area. The rates of CHD were defined for first-degree relatives of cases with isolated defects, grouped by a pathogenic classification scheme. Precurrence risks were found to vary among the groups, and risks for flow lesions were higher than previously reported. The sibling precurrence risk for hypoplastic left heart syndrome (13.5%) was not significantly different from that expected for an autosomal recessive mechanism; the risks for different types of ventricular septal defects (VSD) varied among mechanistic groups. The results indicate that the additive multifactorial model does not adequately account for the risks in all forms of isolated CHD of unknown etiology.

District of Columbia↗

Cardiac and noncardiac malformations: observations in a population-based study.

A regional case-control study of congenital cardiovascular malformations (CCVMs) searches for all live-born infants in the community in whom the cardiac diagnosis has been confirmed by echocardiography, cardiac catheterization, surgery, or autopsy. Their families are studied in comparison to those of a representative sample of resident live-born infants. Detailed descriptions of noncardiac abnormalities are obtained from physician reports and maternal interviews expanded by medical record and death certificate data. Among 1,494 cases and 1,572 controls, chromosomal abnormalities, syndromes, heritable disorders, and suspect syndromes occurred with an overwhelming excess in cases (chromosomes, P less than 10(-4); syndromes/heritable disorders, P less than .005). Abnormalities affecting chromosomes 13, 18, and 21 constituted 93% of the cytogenetic defects. Syndromes and heritable disorders were of 39 types. Nonsyndromic abnormalities were three times more frequent in cases than in controls (P less than .005). Case excesses occurred for central nervous system malformations, eye disorders, major abdominal wall defects, and abnormalities of the alimentary and urinary tracts. Severe anomalies frequent among cases were those which also occur in certain recognized syndromes, and it is suggested that paired combinations of cardiac and other midline anomalies may represent "formes frustes" of syndromes with similar though variable phenotypic expressions. Cleft lip and palate, inguinal hernia, and lower limb anomalies occurred with equal frequency, suggesting their association with CCVMs by chance alone.

Chromosome Aberrations↗

Is diabetes mellitus a teratogen or a coteratogen?

The risk of major and minor congenital malformations was compared in the offspring of diabetic (n = 2,639) and nondiabetic (n = 2,144) women who delivered at the Johns Hopkins Hospital in Baltimore, Maryland, between January 1, 1946 and December 31, 1970. In spite of ample power, there was little evidence of an increased malformation risk in offspring born prior to the onset of overt diabetes in the mother. In offspring born after onset, the overall malformation risk was not increased, but severe multi-organ birth defects occurred at approximately twice the control group rate. It is postulated, therefore, that diabetes may act as a coteratogen enhancing the teratogenic effect of other insults but may not itself cause malformations. That some of its effects may be specific is suggested by the especially high risk of vertebral, lower limb, and urogenital defects, a pattern similar to that reported for the caudal dysgenesis syndrome. To better understand the teratogenic effects associated with diabetes, it may be necessary to consider interactions with other factors and to explore the association between maternal diabetes and caudal dysgenesis.

Adult↗

Changes in alcohol, cigarette, and recreational drug use during pregnancy: implications for intervention.

From the Baltimore-Washington Infant Study, a regional epidemiologic study of congenital cardiovascular malformations, 1,336 mothers of infants selected as controls (a representative sample of the area birth cohort enrolled between April 1, 1981 and September 1, 1984) were studied with respect to alcohol, cigarette, and recreational drug use prior to and during pregnancy. Nearly half of the 1,336 women abstained from any substance use during pregnancy. Of the remainder, half restricted substance use to only alcohol or cigarettes. Only cigarette smokers showed a majority (68.5%) of women failing to successfully quit during pregnancy. Cigarette and recreational drug use during pregnancy was associated with lower socioeconomic status, while alcohol use was associated with higher social status. Cessation of cigarette and recreational drug use was more common among professionals and the college-educated, but these same characteristics, along with higher income, were associated with failure to quit drinking. Younger women were less likely to use alcohol and cigarettes and more likely to successfully quit these habits once adopted. Use of alcohol and tobacco was greater among whites, and recreational drug use was greater among black women, but race was not associated with quitting use of any substance. Length of time trying to become pregnant and the mother's perceived health were not found to be associated with substance use or quitting. This sociodemographic profile suggests subgroups which must be targeted for intervention by the prenatal care provider, as well as intervention strategies.

Adolescent↗

Contractile properties of the shortening rat diaphragm in vitro.

Diaphragmatic fatigue has been defined in terms of the failure of the muscle to continue to generate a given level of tension. Appropriate shortening of the diaphragm is, however, just as important for adequate ventilation. In this study we have examined in vitro the contractile properties of the rat diaphragm under afterloaded isotonic conditions and the effect of fatigue on the ability of the diaphragm to shorten. Shortening of the muscle strips was found to depend on size of afterload, frequency of stimulation, duration of stimulation, and initial length of the muscle. The afterloaded isotonic length-tension relationship coincided with the relationship between length and active isometric tension only for relatively small afterloads. Fatigue of the muscle strips, induced by isometric or afterloaded isotonic contractions, was associated with a decline in the extent of shortening as well as a decrease in active isometric tension. Ability to shorten and ability to develop isometric tension did not decrease to the same extent under all conditions. We conclude that active shortening, as well as active isometric tension, is decreased by muscular fatigue and that changes in these properties can be different depending on experimental conditions. The results suggest that the definition of diaphragmatic fatigue should be expanded to include the ability of the muscle to shorten by an appropriate amount. The results also suggest that measurement of isometric performance may not provide a complete estimate of the overall performance of the fatigued diaphragm.

Animals↗

Physician-patient communication. Understanding congenital heart disease.

Mothers' descriptions of their childrens' congenital heart disease were compared with cardiologists' diagnoses. Maternal understanding was examined with respect to 21 factors using bivariate contingency tables and multiple regression analyses. Of 285 mothers, 36% demonstrated poor comprehension. Maternal understanding was associated with sociodemographic variables but not with factors related to stress. All variables taken in concert that were predictive of understanding explained less than 13% of the variability in maternal knowledge. Distorted perceptions of congenital heart disease may cause unnecessary anxieties, inappropriate restrictions, and impairment of the child's self-perception. The bizarre nature of some of the mothers' incorrect descriptions and the accuracy of responses of mothers in biologic and health care occupations suggest that fundamental ignorance of the cardiovascular system may be of such importance as to minimize the impact of other variables.

Attitude to Health↗

Congenital heart disease: prevalence at livebirth. The Baltimore-Washington Infant Study.

The Baltimore-Washington Infant Study is a regional epidemiologic study of congenital heart disease. Among Infants born in the study area in 1981 and 1982, 664 had a diagnosis of congenital heart disease confirmed in the first year of life by echocardiography, cardiac catheterization, cardiac surgery, or autopsy. The prevalence rate was 3.7/1,000 livebirths for all cases and 2.4/1,000 livebirths for cases confirmed by invasive methods only. Diagnosis-specific prevalence rates of congenital heart disease are compared with those of eight previous case series. Changing diagnostic categorizations in the time span covered and methodological differences resulted in great variation of the data. However, the data of the New England Infant Cardiac Program which used the same case discovery methods showed similar occurrences of major morphologic abnormalities, suggesting that these are stable basic estimates in the eastern United States. For all case series, the rate of confirmed congenital heart disease was approximately 4/1,000 livebirths over the 40-year time span.

Cardiac Catheterization↗

The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals.

We examined changes in spontaneously secreted growth hormone with aging by studying the 24-h integrated concentration of GH (IC-GH) of 173 nonobese subjects (height, greater than or equal to 5%; 7-65 yr of age). There was no significant difference in IC-GH on repeat testing of 13 men or in 23 women studied in the follicular and again in the luteal phase of the menstrual cycle. The level of IC-GH was strongly effected by age; children had the highest mean IC-GH, and there was a decline in IC-GH with increasing age after the second decade of life. The correlation of IC-GH with age was highly significant (r = 0.73; P less than 0.0001). There was no difference in IC-GH between males and females when matched for age. The mean IC-GH at Tanner stage 5 of puberty (7.4 +/- 2.0 ng/ml) was higher than that at stages 2-4 (5.7 +/- 1.4; P less than 0.0005) or that in prepubertal children (5.8 +/- 1.4; P less than 0.001). Thus, age and pubertal status must be carefully considered when interpreting the IC-GH for patients suspected of having deficient or excessive secretion of GH.

Adolescent↗

Temporal changes after death in primate diaphragm muscle oxidative enzyme activity.

We have previously reported that muscle fibers in fresh samples of the diaphragm muscle of prenatal baboons have moderate to high oxidative capacity and are resistant to fatigue in vitro. These conclusions are in conflict with those of others on diaphragmatic muscle fibers studied in autopsy specimens from human infants. Reasons for these divergent interpretations could include species difference and the use of autopsy specimens rather than fresh tissue samples. We have, therefore, tested whether characteristics of human infant diaphragm muscle fibers differ from those of premature baboons, and whether the use of autopsy specimens alters interpretations of histochemical results. Samples obtained from premature, newborn, or adult baboons were quick-frozen immediately after death or after storage for as long as 24 h. Samples were obtained at autopsy from human infants at 4 to 24 h after death. Histochemical assay for NADH-TR activity was performed on cross sections. Samples from baboons at any age showed deterioration with storage, but the muscles from premature and newborn animals were considerably more susceptible to damage than those of adults. Fibers in human infant diaphragm obtained within 10 h of death looked remarkably similar to those of the infant baboons. However, samples obtained at later times after death showed deterioration and loss of oxidative enzyme activity. We conclude that diaphragmatic muscle fibers of humans and nonhuman primates are similar in enzymatic profile, but that elapsed time after death can reduce the intensity of mitochondrial enzyme assays. The decrement in tissue preservation with elapsed time after death is less pronounced in more mature muscles.

Animals↗

Hematologic disorders and congenital cardiovascular malformations: converging lines of research.

In a population-based study on congenital cardiovascular malformations (CCVM), the occurrence of heritable coagulopathies among case parents and not among controls raised the possibility of an etiologic association of CCVM with blood disorders. The literature was searched for evidence that such an association could be biologically plausible. Reported embryologic and clinical data provided confirmatory findings. The heart and blood arise from common angiogenic cells; endothelial cells, the first components of the primitive heart, synthesize coagulation factors; resultant osmotic alterations of embryonic fluids could alter early cardiac morphogenesis. Bleeding diatheses are common in cyanotic and acyanotic patients with CCVM and hemostatic disorders have been reported in some families. CCVM and blood disorders are joint components of several malformation syndromes. The hypothesis of an etiologic relationship between HBD and CCVM needs to be tested in multiple research areas. Future experimental studies should be based on current theories of cardiac morphogenesis to include investigations of embryonic blood in genetic blood disorders. Clinical studies should clarify hematologic alterations in CCVM probands and their families.

Anemia↗

Development of histochemical and functional properties of baboon respiratory muscles.

We assessed morphological, histochemical, and physiological characteristics of respiratory muscles of a non-human primate, Papio cynocephalus, from midgestation through adult life. Samples were taken of diaphragm muscles for histochemical analysis, electron microscopy, and assessment of contractile properties and fatigability. Histochemical analyses were also performed on samples of intercostal muscles. Initially, developing fibers are type IIc but differentiate into types I and IIa fibers by term. We observed no IIb fibers in respiratory muscles of premature baboons. Beginning late in gestation, muscle fibers grew rapidly. After term, IIb fibers were found, and fiber size ranked by increasing mean fiber area became types I, IIa, and IIb. After term, we rarely observed type IIc fibers. In electron micrographs we observed large numbers of interfibrillar mitochondria in all muscle fibers of premature baboons but not in all IIb fibers of adults. Histochemical observations were supported by contractile properties. Muscles of premature baboons had significantly longer contraction and relaxation times than adult muscles. Muscles from premature baboons were more resistant to fatigue than those of adult baboons. We conclude that the fibers of respiratory muscles are high in oxidative capacity and are resistant to fatigue during gestation. Fatigue of the respiratory muscle fibers secondary to low oxidative capacity is not a likely cause of respiratory distress in premature baboons.

Animals↗

Assessment of hospital performance by use of death rates. A recent case history.

This article discusses an analytical approach for integrating hospital death rates. A study of patient mortality in four hospitals in a large metropolitan areas demonstrates the principles underlying this approach. One hospital, which experienced an annual crude death rate almost twice that of the other three, was suspected of providing an inferior quality of care. Case-mix differences among the hospitals introduced a serious bias, however, and were later taken into account. The patients' primary diagnosis was found to be the most important case-mix variable, with a potential for biasing death rate comparisons. After readjustment for case mix, the maximum difference in death rates among the four hospitals was reduced from 19 to four deaths per 1,000 patients. Further analysis of diagnosis-specific mortality supported the thesis that the observed mortality excess was largely attributable to patient referral patterns in the community.

Adolescent↗

Rat muscle structure and metabolism in relation to age and food intake.

Age changes in oxygen consumption and the structural composition of the lateral omohyoideus muscle were studied in adult male rats. The rate were either fed ad libitum (group A) or 60% of the ad libitum intake (group R). An age-related loss in muscle mass did not occur even at advanced ages in group A or group R rats. Muscle fiber diameter decreased with age in both groups but a concomitant increase in the number of fibers prevented a change in muscle mass. The muscles of group R rats contained the same number of fibers as those of group A rats at all ages. The muscles of group A rats showed a progressive loss in rate of resting oxygen consumption until 18 mo of age. A similar but less marked loss in oxygen consumption occurred in the muscles of group R rats. These results provide further evidence that life-prolonging food restriction modulates physiological changes associated with the aging process.

Aging↗