Effects of a physical activity program on metabolic control and cardiovascular fitness in children with insulin-dependent diabetes mellitus.

The purpose of this investigation was to determine the effects of a regular vigorous physical activity program on children aged 5-11 yr with insulin-dependent diabetes mellitus (IDDM). The experimental group of children (N = 9) took part in a 30-min vigorous exercise program three times a week for 12 wk; the control group (N = 10) did not. Hemoglobin A1 (HbA1) and fasting blood glucose (FBG) were used to determine metabolic control. Oxygen consumption was evaluated by treadmill testing and analyses of expired air. The experimental group significantly (P less than 0.05) decreased their HbA1 and FBG while the control group showed no change. The experimental group significantly (P less than 0.05) increased their peak aerobic capacity (ml/kg . min) when compared with baseline values (47.14 +/- 1.94 versus 50.69 +/- 1.30). It was concluded that a carefully applied program of regular vigorous physical activity can beneficially influence metabolic control and cardiovascular fitness in young children with IDDM.

Bone mineral density and its change in pre-and perimenopausal white women: the Michigan Bone Health Study.

There is a need to better understand potential bone mineral density (BMD) loss during the menopausal transition since this period may include the initiation of interventions. The study purpose was to determine if there was BMD loss at the femoral neck, lumbar spine, or total body bone sites in a population-based study of women approaching or transitioning the midlife. The 583 enrollees were 25-45 years of age at the first of four annual measurements from 1992 through 1996. Bone mineral content and bone width were measured using dual-energy X-ray absorptiometry. Considering all enrollees collectively, there was a significant 3-year decline (1%) in BMD at the femoral neck over the 3-year period (p = 0.076). There was no significant annual change in the lumbar spine (p = 0.11), and a significant annual increase in the total body BMD (p = 0.0003). Within subgroups and cross-sectionally, BMD values of the femoral neck were 5% lower in women classified as perimenopausal compared with premenopausal enrollees; BMD was 3% and 1% lower at the lumbar spine and total body site, respectively. Longitudinally, among perimenopausal women, a double oophorectomy was associated with BMD loss in the spine (p = 0.0003), even though 75-85% of these women had a hormone replacement prescription at some time during the study period. In summary, the site with evidence of loss was the femoral neck, specifically among perimenopausal women. There was little evidence of substantial total body or lumbar spine BMD loss in premenopausal women with ovaries who maintained follicle-stimulating hormone levels < 20 mIU/l in the early follicular period. Double oophorectomy, even with hormone replacement, was associated with bone loss.

Plasma norepinephrine variations with dietary sodium intake.

Plasma catecholamine and renin activity levels were measured across a range of dietary sodium intakes (10--300 mEq/day) in 20 normal male volunteers. Supine plasma norepinephrine levels presented a triphasic pattern in relation to urine sodium, whereas epinephrine levels were not significantly altered by sodium intake, and renin showed the well-known hyperbolic relationship to urine sodium excretion. Highest supine norepinephrine values occurred at low salt intakes, the lowest when sodium excretion was between 100 and 180 mEq/day, and intermediate when sodium excretion was greater than 180 mEq/day. These findings show that sodium intake is an important consideration in the interpretation of plasma norepinephrine levels.

Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease.

BACKGROUND: Decreased hippocampal volume is observed in patients with Cushing's syndrome and other conditions associated with elevated cortisol levels, stress, or both. Reversibility of hippocampal neuronal atrophy resulting from stress occurs in animals. Our study investigated the potential for reversibility of human hippocampal atrophy. METHODS: The study included 22 patients with Cushing's disease. Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment. RESULTS: Following treatment, hippocampal formation volume (HFV) increased by up to 10%. The mean percent change (3.2 +/- 2.5) was significantly greater (p < .04) than that of the comparison structure, caudate head volume (1.5 +/- 3.4). Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol (r = -.61, p < .01). This relationship strengthened after adjustments for age, duration of disease, and months elapsed since surgery (r = -.70, p < .001). There was no significant correlation between caudate head volume change and magnitude of cortisol decrease. CONCLUSIONS: Changes in human HFV associated with sustained hypercortisolemia are reversible, at least in part, once cortisol levels decrease. While many brain regions are likely affected by hypercortisolemia, the human hippocampus exhibits increased sensitivity to cortisol, affecting both volume loss and recovery.

Role of calciotrophic hormones in calcium mobilization of lactation.

The postpartum period can be a time when profound changes in calcium metabolism and bone mineral density (BMD) occur, particularly in association with lactation. We investigated the hypothesis that calciotrophic hormones [1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone (PTH)] are different by lactation practice or hormone status [PTH-related peptide (PTHrP), estradiol, and prolactin] and have a potential role in the bone loss and recovery associated with lactation. 1,25-Dihydroxyvitamin D, 25-hydroxyvitamin D, PTH, femoral BMD, PTHrP, prolactin, estradiol, and bone turnover markers were measured at 2 wk and at 2, 4, 6, 12, and 18 mo postparturition in 115 postpartum women aged 20-40 y (parity: 0-1). Lumbar spine BMD was measured at 2 wk and at 6, 12, and 18 mo during the postpartum period. PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D concentrations were nonlinear across the 18-mo postpartum period. Between baseline and 18 mo postparturition, PTH and 1,25-dihydroxyvitamin D concentrations did not decline, while there was a substantial decline in 25-hydroxyvitamin D concentrations. PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D concentrations did not differ by lactation practice or by PTHrP, estradiol, or prolactin status. These classic calciotrophic hormones were not associated with concentrations of bone turnover markers or changes in BMD in lactating women. In summary, patterns of change in calciotrophic hormones (PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D) in the 18-mo postpartum period appeared to be independent of PTHrP, estradiol, prolactin, or lactation status and were not associated with bone turnover markers. These data do not support the hypothesis that these three calciotrophic hormones are a central part of the calcium mobilization associated with the bone loss of lactation.

Blood pressure and blood group markers: association with the MN locus.

The relationship of blood pressure levels to 12 blood, salivary and serum protein polymorphisms is reported for a sample of 4000+ adult Caucasians from Tecumseh, Michigan. Males with the MN phenotype had significantly higher unadjusted systolic and diastolic blood pressures than those who were homozygous MM or NN. When blood pressure was adjusted for age and weight, males who were Duffy (a-) had higher diastolic pressures than those who were Duffy (a+), and females who were Kidd (b-) had higher diastolic pressures than females who were Kidd (b+). A review of studies reporting on MN- blood pressure associations indicates that six of the eight presented significant findings. These findings, and others from the literature, present evidence that the MN locus (and possibly the Jk locus) actively participates in controlling the response to environmental/dietary stimuli affecting differences in blood pressure. We suggest that the MN blood group be investigated further, particularly vis-à-vis physiological parameters known to be related to blood pressure.

The role of the primary care physician in the care of children with serious heart disease.

OBJECTIVE: To determine the roles of primary care physicians and specialists in the medical care of children with serious heart disease. SETTING: Pediatric Cardiology Division; Tertiary Care Children's Hospital. SUBJECTS: Convenience sample of parents, primary care physicians, and pediatric cardiologists of 92 children with serious heart disease. DESIGN: Questionnaire study; questionnaires based on 16 medical care needs, encompassing basic primary care services, care specific to the child's heart disease and general issues related to chronic illness. RESULTS: All children had a primary care physician (PCP), and both they and the parents (P) reported high utilization of PCP for basic primary care services. However, there was little involvement of PCP in providing care for virtually any aspect of the child's heart disease. Parents expressed a low level of confidence in the ability of PCP in general or their child's own PCP to meet many of their child's medical care needs. Both PCP and pediatric cardiologists (PC) were significantly more likely than parents to see a role for PCP in providing for care specific to the heart disease as well as more general issues related to chronic illness. PC and PCP generally agreed about the role PCP should play, although PC saw a bigger role for PCP in providing advice about the child's activity than PCP themselves did. PC were less likely to see the PCP as able to follow the child for long term complications than PCP did. PC were more likely than PCP to believe that PCP were too busy or were inadequately reimbursed to care for children with serious heart disease. Only about one-third of parents reported discussing psychosocial, family, economic, or genetic issues with any provider, and PCP were rarely involved in these aspects of chronic illness. CONCLUSIONS: Primary care physicians do not take an active role in managing either the condition-specific or the more general aspects of this serious chronic childhood illness. With appropriate information and support from their specialist colleagues primary care physicians could provide much of the care for this group of children. Generalists and specialists are both responsible for educating and influencing parents about the role primary care physicians can play in caring for children with serious chronic illness.

The effect of bronchopulmonary dysplasia on growth at school age.

OBJECTIVE: To determine the effect of bronchopulmonary dysplasia (BPD) on growth at school age. DESIGN: A prospective cohort study. METHODS: The sample included 406 children selected from a reconstructed cohort of infants of very low birth weight previously enrolled in a multisite, randomized, controlled clinical trial. The children were contacted at 8 to 10 years of age. Height, weight, and head circumference (HC) were measured. Possible confounders including sociodemographic data, and neonatal factors were also recorded. RESULTS: The children in the BPD group were significantly smaller in weight (z score, -0.50 +/- 1.19 SD vs -0.06 +/- 1.30 SD) and HC (z score, -1.41 +/- 1.32 SD vs -0.63 +/- 1.62 SD) than those without BPD. However, after controlling for cofounders (using analysis of covariance), no significant differences were demonstrated between the two groups. Power analyses showed that a difference of at least 0.43 z score units could have been detected. The previously documented associations between BPD and suspected confounders were reconfirmed. CONCLUSIONS: Significant differences were noted between children with and without BPD for weight and HC but not height. When possible confounders were taken into account, the differences were no longer appreciated. Thus, the previously reported poor growth in children with BPD may have been related to other factors and not necessarily to BPD.

Intraaortic balloon pumping 1967 through 1982: analysis of complications in 733 patients.

Between June 1967 and December 1982, 872 attempts at intraaortic balloon pumping (IABP) were made in 733 patients. Nearly 75% of the patients were men; the proportion of women has increased in recent years. The principal indication for IABP support initially was cardiogenic shock, but over the years, preoperative support, weaning from cardiopulmonary bypass and unstable angina have become the primary indications. Complications of IABP were classified and distributed by severity (minor: I [15%] and II [26%]; major: III [3%] and IV [1%]) and type ([vascular [22%], infectious [22%], and bleeding [7%]). Vascular complication rates were higher in women (32 vs 18%; p = 0.0001), in diabetic patients (32 vs 20%, p = 0.003), and in hypertensive patients (27 vs 20%, p = 0.02). These did not vary with the duration of IABP support (range of duration 0 to 76 days). The rate of infectious complications was related to location where IABP was performed (coronary care unit 26%, operating room 12%). The rate of fever and bacteremia increased significantly with duration of IABP support, but the rate of local wound infection did not. In conclusion, most IABP complications are minor, resolve after balloon removal, are related to vascular status of the patient and, with the exception of bacteremia, are independent of IABP duration.

Risks associated with intraaortic balloon pumping in patients with and without diabetes mellitus.

Between 1967 and 1982, intraaortic balloon pumping (IABP) was attempted in 733 patients. Of these, 132 were diabetic: 51 patients were managed with diet alone, 46 patients took oral hypoglycemic agents and 35 patients required insulin. Vascular complications associated with IABP occurred in 34% of the insulin-dependent diabetics, in 18% of other diabetics and in 14% of nondiabetic patients. Infectious complications were 37, 22 and 25%, respectively. Seventy-five diabetic patients (57%) were discharged alive from the hospital after balloon pumping, essentially the same proportion as among nondiabetic patients (58%). It is concluded that although diabetics incur a higher complication rate, IABP is not contraindicated.

Discordant changes in plasma ACTH and beta-lipotropin/beta-endorphin levels in Cushing's disease patients with depression.

Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and beta-lipotropin/beta-endorphin (beta-LPH/beta-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean [+/- SD] depressed mood score = 0.17 +/- 0.4; modified Hamilton Depression scale score = 7.6 +/- 4.5) and five as severely depressed (mean depressed mood score = 2.4 +/- 0.5; modified Hamilton Depression scale score = 15 +/- 5.6) (p < 0.05). ACTH and beta-LPH/beta-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and beta-LPH/beta-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed = 90.0 +/- 16.7; severely depressed = 34.6 +/- 8.7 (p < 0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0 mg dexamethasone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term and long-term outcomes after bilateral lung volume reduction surgery : prediction by quantitative CT.

OBJECTIVES: To evaluate selection criteria and duration of benefit for patients undergoing lung volume reduction surgery (LVRS). METHODS: Eighty-nine consecutive patients with severe emphysema who underwent bilateral LVRS were prospectively followed up for up to 3 years. Patients underwent preoperative pulmonary function testing, 6-min walk, chest CT, and answered a baseline dyspnea questionnaire. CT scans in 65 patients were analyzed for emphysema extent and distribution using the percentage of emphysema in the lung, percentage of normal lower lung, and the CT emphysema ratio (CTR, an index of the craniocaudal distribution of emphysema). All patients underwent at least 6 weeks of pulmonary rehabilitation prior to surgery. Outcome measures were FEV(1), 6-min walk distance, and transitional dyspnea index (TDI). RESULTS: Compared to baseline, FEV(1) was significantly increased at 3, 6, 12, 18, 24, and 36 months after surgery (p < or = 0.008). The 6-min walk distance increased from 871 feet (baseline) to 1,110 feet (3 months), 1,214 feet (6 months), 1,326 feet (12 months), 1,342 feet (18 months), 1,371 feet (24 months), and 1,390 feet (36 months) after surgery. Despite a decline in FEV(1) over time, 6-min walk distance was preserved. Dyspnea as measured by TDI improved at 3, 6, 12, 18, 24, and 36 months after surgery. A high CTR was the best predictor of a 12% increase over baseline and an absolute increase of 200 mL in FEV(1), although with a low area under the receiver operating characteristic curve. In addition, the sensitivity and negative predictive value of the CTR were limited. No radiographic or physiologic predictor was able to consistently predict a successful increase in walk distance or TDI. CONCLUSION: LVRS improves pulmonary function, decreases dyspnea, and enhances exercise capacity in many patients with severe emphysema, although improvement wanes 36 months after surgery.

Sources of variability in quantitative levels of alcohol use in a total community: sociodemographic and psychosocial correlates.

This article describes the transformation of reported alcohol consumption into a quantitative variable, Standardized Alcohol Intake (SAI), which is used to investigate various sociodemographic and psychosocial factors as correlates of alcohol use in a total community sample (N = 1672), in Tecumseh, Michigan. Statistically significant relations were obtained between alcohol usage and marital status, education, smoking status, and church attendance with the latter accounting for the 15% of the variability in drinking. On measures of personality, SAI was positively and significantly associated with level of activity, sociability, impulsivity, and extraversion. For drinkers, their attitudes toward drinking and changes in mood varied significantly in relation to the amount consumed. These findings are important and necessary for the appropriate control of these correlates in the future study of familial aggregation of SAI in the Tecumseh community.

Some statistical implications of rounding in the College of American Pathologists Survey.

Quantitative measurements of constituent concentrations of Survey specimens are generally recorded to the nearest integer or to the nearest tenth. Questions have arisen as to whether this degree of rounding of measurements is appropriate when available laboratory equipment can determine results more precisely. Statisticians have studied the effects of rounding off on an variety of standard statistical procedures. In this report biases that may result for estimates of the mean and variance from several typical data sets obtained in the 1975 College of American Pathologists (CAP) Survey are examined. The study indicates that the amount of bias in the sample mean and variance is generally minimal.

The distribution of selected hematology measurements in the CAP survey.

Investigation of the 1978 CAP Hematology Survey results for hemoglobin, hematocrit, erythrocyte count, leukocyte count, prothrombin time, and partial thromboplastin time with respect to the assumption of normality and the method for detecting outliers was performed. The findings indicate that the assumption of normality, while not exactly valid, is reasonable for the purposes of the Survey, but that the method of determining outliers may be too stringent in the case of hemoglobin, hematocrit, erythrocyte count, and leukocyte count, and not appropriate for prothrombin time and partial thromboplastin time. These findings are similar to those reported earlier for selected chemistry and immunology constituents in the CAP Survey.

Normality and other statistical considerations as they relate to selected quantitative measures in the CAP survey.

Investigation of the CAP statistical reports for quantitative tests with respect to the assumption of normality and the method for detecting outliers was performed. Specifically, laboratory measurements of several constituents from the Comprehensive Survey for 1975 were examined. The findings indicate that the assumption of normality, while not exactly valid, is reasonable and not deleterious to the purpose of the Survey, but that the method of determining outliers may be too stringent. A less strict, simpler outlier procedure is suggested as an alternative. It is also observed that other evaluation procedures would be available if more significant digits were reported for the laboratory measurements.

An evaluation of statistical procedures designed to detect outliers resulting from a light degree of contamination in random samples of moderate size.

The literature on statistical outlier procedures applicable to the CAP Survey program is briefly reviewed. Limited Monte Carlo evaluations of selected procedures were performed. For a light degree of contamination in random samples of moderate size, it is shown that the application of these procedures has little effect on estimates of measures of central tendency and spread. Moreover, in this situation these procedures detect a very small percentage of the outliners.

Combined vs. single-drug studies of susceptibilities of Mycobacterium kansasii to isoniazid, streptomycin, and ethambutol.

The effects of combined drugs were compared uith the effects of single drugs in vitro against Mycobacterium kansasii. The single drugs isoniazid 1.0 microgram/ml, streptomycin 2.0 microgram/ml, and ethambutol 5.0 microgram/ml and the combinations of 1.0 microgram/ml isoniazid and 2.0 microgram/ml streptomycin, 1.0 microgram/ml isoniazid and 5.0 ethambutal and 1.0 microgram/ml isoniazid, 2.0 microgram/ml streptomycin and 5.0 microgram/ml ethambutol were evaluated as to their effects on M. kansasii organisms from 22 patients with pulmonary mycobacterial disease. These drugs were incorporated into Middlebrook 7H11 medium. Colonial growth was then observed and assigned numerical values for statistical analysis. The results showed that isoniazid was not significantly better than ethambutol. Streptomycin, however, was significantly better than both isoniazid and ethambutol alone. The double combinations were better than the single drugs, with isoniazid--streptomycin being better than isoniazid--ethambutol. The combination isoniazid--ethambutol was not significantly better than streptomycin alone. However, the triple combination of isoniazid--streptomycin--ethambutol was markedly better than all single drugs, better than isoniazid--ethambutol, but not better than isoniazid--streptomycin. Combined-drug testing thus showed a pattern of susceptibility not demonstrated by single-drug testing.

Longitudinal influence of age, menopause, hormone replacement therapy, and other medications on parotid flow rates in healthy women.

BACKGROUND: Recent investigations have demonstrated that parotid salivary dysfunction is not a normal process of aging, but may be the consequence of systemic conditions and their treatment, including medications and menopause. The purpose of this study was to assess longitudinally the influence of age, menopausal status, hormone replacement therapy, and other medications on stimulated parotid flow rates (SPFRs) in healthy women. METHODS: Medical diagnoses, menopausal status, medication utilization, and 2% citric acid stimulated parotid salivas were collected from 396 women, aged 21 to 96 years, from the Baltimore Longitudinal Study of Aging (National Institute on Aging, National Institutes of Health) over a 17-year span by three investigators. RESULTS: There was no overall longitudinal effect of time on SPFR. Age at first visit was a significant predictor of a decrease in SPFR when adjusted for time and xerostomic medications. However, the deleterious effect of taking one xerostomic medication was equivalent to approximately 14 years of aging. Menopausal status and hormone replacement therapy were not consistently associated with diminished SPFR. CONCLUSIONS: These results suggest that menopause and hormone replacement therapy are not associated with parotid salivary dysfunction. Aging may have a statistically significant yet small deleterious influence on SPFR; however, the adverse influence of xerostomic medications is much larger.

Intravenous ritodrine therapy: a comparison between twin and singleton gestations.

The purpose of this study was to determine whether or not guidelines for intravenous ritodrine therapy for singleton pregnancies in premature labor also apply for twin gestations. Between January 1982 and March 1985, 43 (18%) of 239 women admitted in premature labor had twin fetuses. Intravenous ritodrine therapy was used for four or more hours in 23 of these pregnancies. Compared with a matched group of 23 singleton pregnancies, increases in maternal and fetal heart rates and decreases in maternal diastolic blood pressures were not significantly different. Undesired cardiovascular effects were no more common and usually occurred during the initial infusion period when the dose was increased most rapidly. The averaged doses, duration of therapy, and delays in delivery were also similar between the twin and singleton groups.