Impaired growth hormone secretion in the adult population: relation to age and adiposity.

Growth hormone (GH) release was studied in adults of normal stature, ages 21-86 yr. The subjects were 85-115% of ideal body weight, between the 5th and 95th percentiles in height, and free of active or progressive disease. 9 to 12 individuals in each decade from thirds to ninth were evaluated. The following criteria of GH status were measured: serum GH concentration, analyzed by radioimmunoassay at half-hour intervals for 4 h after onset of sleep, and at 1-h intervals from 8 a.m. to 4 p.m. in 52 subjects; daily retention of N, P, and K in response to 0.168 U human (h)GH/kg body wt3/4/day in 18 subjects; and plasma somatomedin C (SmC) level before and during exogenous hGH treatment in 18 subjects. All 10 individuals, 20-29 yr old, released substantial amounts of endogenous GH during both day and night (average peak serum GH obtained during day and night was 7.3 and 20.3 ng/ml, respectively); average plasma SmC was 1.43 U/ml (95% tolerance limits, 0.64-2.22 U/ml). There was no significant effect of exogenous hGH on elemental balances or on plasma SmC. In contrast, 6 of 12 individuals 60-79 yr old showed the following evidences of impaired GH release; peak waking and sleeping serum GH less than 4 ng/ml; plasma SmC less than 0.38 U/ml; a significant retention in N, P, and K; and a significant rise in plasma SmC, in response to exogenous hGH. Plasma SmC, serum GH during sleep, serum GH during the day, retentions of N, P, and K in response to exogenous hGH, and rise in plasma SmC in response to hGH were all intercorrelated (P less than 0.05). Plasma SmC less than 0.38 U/ml corresponded to peak nocturnal serum GH less than 4 ng/ml. The prevalence of plasma SmC less than 0.38 U/ml increased progressively from age 20 to 90: third decade, 0%; fourth, 11%; fifth, 20%; sixth, 22%; seventh, 42%; eight, 55%; and ninth, 55%. Within each decade, plasma SmC was inversely related to adiposity.

Predictors of progression from impaired glucose tolerance to NIDDM: an analysis of six prospective studies.

Risk factors associated with the progression from impaired glucose tolerance (IGT) to NIDDM were examined in data from six prospective studies. IGT and NIDDM were defined in all studies by World Health Organization (WHO) criteria, and baseline risk factors were measured at the time of first recognition of IGT. The studies varied in size from 177 to 693 participants with IGT, and included men and women followed from 2 to 27 years after the recognition of IGT. Across the six studies, the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years. Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence, incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels, but increased linearly with increasing 2-h postchallenge glucose quartiles. Incidence rates were higher among the Hispanic, Mexican-American, Pima, and Nauruan populations than among Caucasians. The effect of baseline age on NIDDM incidence rates differed among the studies; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies. In all studies, estimates of obesity (including BMI, waist-to-hip ratio, and waist circumference) were positively associated with NIDDM incidence. BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately, but not in the three studies with the highest NIDDM incidence rates. Sex and family history of diabetes were generally not related to NIDDM progression. This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements. The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention.

Vertex-corrected blood pressure in black girls. Relation to obesity, glucose, and cations.

Correlates of resting blood pressure (BP) were explored among 32 inner-city, black girls, ages 11.7 to 13.9 years, a sample drawn from the second and fourth quartiles of the BP distribution in an earlier school survey. Customary BP measurements in the seated position were corrected for the height of the arterial column extending from the BP cuff to the top (vertex) of each girl's head. This vertex correction procedure has previously been shown to eliminate the childhood association between mean arterial pressure and age. Vertex-corrected systolic BP was correlated individually (p less than 0.03) with serum fasting glucose, ionized calcium, sodium, and calculated osmolality. The BP association with serum glucose did not persist after an oral sucrose challenge. Vertex-corrected diastolic BP was correlated individually (p less than 0.02) with serum ionized calcium and four indices of obesity, the best correlated of which was the subscapular skinfold (r = 0.66, p = 0.0001). Vertex-corrected BPs generally provided stronger correlations than customary (uncorrected) BPs with the variables of interest. Correlations with seated BPs were generally stronger than those with supine BPs. By multiple regression analysis, seated vertex-corrected systolic BP was related directly to serum fasting glucose and ionized calcium and inversely to pulse rate (R2 = 0.53). Seated vertex-corrected diastolic BP was related directly to subscapular skinfold and calculated osmolality (R2 = 0.54). Vertex correction may facilitate clinical or epidemiological studies of early hypertension.

Blood pressure, plasma volume, and catecholamine levels during enalapril therapy in blacks with hypertension.

The effect of enalapril, an antihypertensive inhibitor of angiotensin-converting enzyme, on plasma catecholamine levels and plasma volume (PV) has not been well established. In a randomized, double-blind study, 29 subjects (28 blacks and one white) received one of the following dosing regimens: hydrochlorothiazide (HCTZ), 25 mg twice a day (group 1; n = 12); enalapril, 10 mg twice a day (group 2; n = 12); or enalapril, 10 mg twice a day, with HCTZ, 25 mg twice a day (group 3; n = 5). Dosages were doubled after 4 wk if diastolic blood pressure was greater than or equal to 90 mm Hg. After 8 wk of therapy, supine blood pressure decreased by 24.1/16.0 mm Hg (systolic/diastolic) in group 1, by 10.8/4.0 mm Hg in group 2, and by 48.0/27.8 mm Hg in group 3. Mean values of supine plasma levels of norepinephrine, epinephrine, and dopamine did not change with therapy. PV fell 7.9% in group 1, 1.3% in group 2, and 5.0% in group 3. There were no correlations between changes in PV and blood pressure, but a decrease in PV correlated with an increase in plasma norepinephrine levels in the group treated with HCTZ alone (r = -0.65) and in all 29 subjects combined (r = -0.45). Enalapril alone was not very effective in lowering blood pressure in these subjects, but the combination of enalapril with HCTZ was very effective. There was no evidence of a direct effect of enalapril on the sympathetic nervous system or on PV.

Report of a National Institutes of Health--Centers for Disease Control and Prevention workshop on the feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons.

A workshop was convened in 1997 by the National Institutes of Health and the Centers for Disease Control and Prevention to consider the need for and feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons. Although the benefits of weight loss in obese individuals may seem obvious, little information is available showing that intentional weight loss improves long-term health outcomes. Observational studies may be unable to provide convincing answers about the magnitude and direction of the health effects of intentional weight loss. Workshop participants agreed that a well-designed randomized clinical trial could answer several questions necessary for developing a rational clinical and public health policy for treating obesity. Such information will ultimately provide needed guidance on the risks and benefits of weight loss to health care providers and payers, as well as to millions of obese Americans.

A method of screening for growth hormone deficiency using anthropometrics.

Among children less than 3rd percentile in height, less than 1% are deficient in endogenous growth hormone, while 80% have no recognizable organic cause for short stature, and are termed normal variants. This study investigated whether anthropometric evaluation can distinguish growth hormone-deficient from normal variant children. Height, weight, midarm circumference and 10 skinfold thicknesses were measured in 24 growth hormone-deficient and 26 normal variant children; indices of linear growth, adiposity, and lean body mass were derived from these. All these variables were analyzed statistically by discriminant analysis. This led to a screening formula, here called a "Z-function," based only on height and five skinfolds (abdomen, back, chest, knee, and calf). The Z-function classified correctly all but two growth hormone-deficients and two normal variants. Because of the small and possibly inhomogeneous sample, the particular formula developed here is not recommended for general use, but these preliminary findings show that a simple anthropometric screening test is indeed feasible, and could be useful in pediatric practice.

Remission of nephrotic syndrome in type 1 diabetes: long-term follow-up of patients in the Captopril Study.

In 1994, we reported a 3.4 +/- 0.8 year follow-up of the eight patients who experienced remission of nephrotic syndrome during the Collaborative Study Group-sponsored, multicenter trial of captopril therapy in patients with type 1 diabetes with nephropathy (Captopril Study). Of the 409 patients randomized to treatment on the Captopril Study, 108 had nephrotic syndrome (24-hour proteinuria >/= 3.5 g of protein) at baseline. Of these 108 patients, 8 experienced remission of nephrotic syndrome (proteinuria

Determinants of preterm delivery in low-risk pregnancies. The RADIUS Study Group.

From 14,948 low-risk singleton pregnancies, we calculated incidence, risk ratios, and attributable risks for characteristics associated with spontaneous and medically induced preterm delivery. There were 754 women who gave birth prior to 37 weeks of gestation (50.4/1000 deliveries). The greatest fraction of the incidence of prematurity among low-risk pregnancies was due to unknown factors associated with carrying a first live birth, regardless of preterm delivery mechanism (i.e., spontaneous labor, PROM, medical intervention), with population-attributable risk percents (PAR%) ranging from 16.0 to 30.5%. Other than nulliparity, male sex of the fetus accounted for the greatest fraction of spontaneous labor-induced prematurity incidence (PAR% = 13.6%), and maternal age greater than 30 years or a positive urine culture accounted for the greatest fraction of PROM-induced prematurity incidence (PAR% = 7.9 and 6.7, respectively). All other risk factors for either preterm labor or PROM accounted for less than 5% of the incidence. Three characteristics explained a large fraction of medically induced prematurity: women over 150 pounds at the onset of pregnancy (PAR% = 23.8), a > or = 2+ prenatal urine protein (PAR% = 18.7%), and cigarette smoking during the first trimester (PAR% = 8.6). Our results suggest known risk factors may explain only a small fraction of spontaneous preterm delivery incidence in low-risk pregnancies.

Suppurative mediastinitis after open heart surgery. A case control study of risk factors.

Suppurative mediastinitis occurred in 68 of 9,965 patients (0.7 percent) who underwent median sternotomy at Emory University Hospital from 1973 through 1982. Case-control methodology was used to identify preoperative, intraoperative, and postoperative risk factors for the development of poststernotomy mediastinitis. The following 12 individually significant risk factors were identified by univariate analysis: preoperative factors: history of chronic obstructive pulmonary disease (COPD), history of prior sternotomy, pyuria, low ejection fraction, and high left ventricular end-diastolic pressure; intraoperative factors: valvular or aortic aneurysm surgery, prolonged bypass pump time, repeat placement on bypass, duration of surgery; and postoperative factors: surgical reexploration due to postoperative hemorrhage, cardiopulmonary resuscitation in the immediate postoperative period, prolonged time (greater than 48 hours) on mechanical ventilation. By logistic regression analysis, three of these factors were found to be associated independently with increased odds of developing mediastinitis: duration of surgery, history of COPD, and prolonged postoperative mechanical ventilation.

Presence of the "Beaumont" protein in serum of oral contraceptive users.

The level of the "Beaumont" protein present in serum was measured by a population of 223 black and 76 Caucasian women with different exposures to oral contraceptives (OCs). No differences were found in the values in nonusers, past users, current users, or new users of OCs. The values were higher in black nonusers and users than in comparable Caucasian groups, suggesting a racial difference. A group of 55 thrombotic women were subclassified by type of thrombosis and exposure to OC therapy. No significant difference was seen between the values in thrombotic women exposed or not exposed to OCs. A similar result was obtained when the types of thrombosis (arterial or venous) were compared. These results do not confirm Beaumont's hypothesis that antibodies are induced by contraceptive steroids in a subgroup of women on OC therapy.

Prolactin and blood pressure responses to perphenazine in human subjects: comparison of the oral and intramuscular routes.

Although several phenothiazines are known to stimulate prolactin (PRL) secretion, only chlorpromazine is in general use for this purpose in humans. However, chlorpromazine has severe sedative and hypotensive effects. Therefore, the effects of perphenazine on human PRL release and on blood pressure were evaluated. Perphenazine was administered orally (8mg) and intramuscularly (5mg and 2mg) to determine the optimal route and dose for evaluating PRL release. The postural hypotensive effect of perphenazine was evaluated with the 2mg intramuscular (IM) dose. The mean time of peak PRL response (hr +/- SD) was significantly shorter (p less than 0.05) for the 5mg IM (1.7 +/- 0.4) than the oral (4.5 +/- 0.6) route. Also, the mean ratio of peak/baseline PRL was significantly greater for the 5mg IM (8.87 +/- 5.69) than the oral (5.12 +/- 2.90) route. The major side-effect produced by perphenazine was drowsiness, which was moderate to severe with the 5mg IM dose. A lower IM dose (2 mg) retained PRL releasing activity, reduced drowsiness, and did not produce hypotension. For clinical testing, intramuscular perphenazine is preferred over oral perphenazine because of the shorter latency period and the higher PRL levels. Intramuscular perphenazine (2 mg) is preferred to chlorpromazine since it did not produce a clinically significant hypotensive effect. This is the first report on the dynamic responses of PRL and blood pressure to intramuscular perphenazine in humans.

Prediction of children's blood lead levels on the basis of household-specific soil lead levels.

To help guide policy decisions about removing lead-contaminated soils, the authors estimated a regression model for predicting a child's blood lead level on the basis of his or her household-specific soil lead level. The data analyzed were blood lead levels (1-45 micrograms/dl) and household-specific soil lead levels (53-20,700 ppm) of 596 children aged 1-5 years who lived in the Helena Valley of Montana and the Silver Valley of Idaho during August 1983. A non-threshold, multiple linear regression model indicated that the estimated mean natural log transformed blood lead level increased by 0.231 micrograms/dl for each unit increase in natural log transformed soil lead level (ppm), after adjusting for the average number of daily outdoor play hours and whether someone in the household smoked. The model predicted that, at a soil lead level of 1,000 ppm, a child who does not play outside and who does not live in a household where someone smokes would be at low risk of lead toxicity (blood lead level between 4 and 24 micrograms/dl).

IgG subclasses in nonallergic children with chronic chest symptoms.

Immunoglobulin and IgG subclass measurements were made on sera from 37 children thought to have asthma whose chronic chest symptoms were unexplained by allergy. There was a higher proportion of low or low-normal levels of IgG subclasses 1, 2, and 4 in these children than in normal children. Those who had low serum IgG values on initial measurement had a higher proportion of low or low-normal levels of IgG1, IgG2, and IgG4; those who had normal IgG values had a higher proportion of low or low-normal levels of IgG2 and IgG4. Thus a normal serum concentration of IgG did not exclude the possibility of an abnormal level of IgG2 or IgG4. Our experience suggests that abnormal levels of IgG subclasses might play an etiologic role in the chronic chest symptoms in some of these children.

Racial differences in survival of women with endometrial cancer.

The hypothesis that white women with endometrial cancer survive longer than black women with this disease was evaluated in a retrospective analysis of a population-based, prospective cohort study. All female residents of metropolitan Atlanta with a first diagnosis of primary endometrial cancer from 1978 through 1982 were eligible for inclusion. The 628 white and 105 black women were followed up through June 1984 to determine survivorship. Race was evaluated as a prognostic factor with univariate, multivariate, and excess death rate analyses. Overall, an estimated 89.2% of whites and 61.6% of blacks survived 3 years from the time of diagnosis. Although black women tended to have more advanced disease at the time of diagnosis and a higher proportion of undifferentiated malignancies, the racial difference in survival persisted after adjustment for these factors. When initial therapy was considered, race remained a significant prognostic determinant among women who did not receive radiation therapy.

First-order clearance of plasma galactose: the effect of liver disease.

Galactose clearance kinetics at plasma concentrations of 0.01-0.1 mg/ml were studied during continuous infusion of 25-100 mg D-galactose per minute. In 10 subjects, plasma galactose vs. time curves during 140-min infusion, and 60 min thereafter, showed the data to fit a single-compartment model and attain 95% of plasma steady state by 80 min. Doubling the infusion rate in 14 subjects resulted in an 8% reduction in clearance at the higher rate. Hepatic extraction in normal subjects was 94%, while in cirrhotics it was 79%. Day-to-day reproducibility in 11 subjects gave a coefficient of variation of 4.5%. Extrahepatic clearance showed 2% of the total to occur in the urine, and 2.3% to occur by erythrocyte metabolism. The overall mean (+/-SD) clearance in the normal subjects of 1378 +/- 218 ml/min was significantly (p less than 0.05) greater than for the stable cirrhotics at 918 +/- 279 ml/min, but not significantly different from patients with acute hepatocellular damage at 1186 +/- 300 ml/min. This index gives flow-dependent hepatic clearance, and provides a noninvasive measure of effective liver blood flow.

Relationship between serum IgG2 concentrations and antibody responses to pneumococcal polysaccharides in children with chronic chest symptoms.

We measured IgG-class antibodies to 12 pneumococcal antigens pre- and post-immunization with polyvalent pneumococcal vaccine in 31 children who had experienced chronic chest symptoms. The purpose of the study was to determine the relation of IgG subclasses, especially IgG2, to the subjects' antibody responses to bacterial polysaccharide antigens, to see if measuring IgG subclasses would predict these responses. Twenty-nine children (90%) had low or low-normal levels of one or more IgG subclasses, including 20 out of 31 (65%) with low or low-normal levels of IgG2. Children studied had a relatively poor increase in levels of antibody to 10 of the 12 pneumococcal vaccine antigens investigated. Both pre- and post-immunization antibody levels were related to pre-immune serum concentrations of IgG2. Pre-immunization antibody levels were strongly related to post-immunization levels; when post-immunization antibody levels were adjusted for pre-immunization levels by partial correlation, the correlation between anticapsular antibody level post-immunization and IgG2 was no longer significant. Thus, in children with chronic chest symptoms, levels of antibody measured at a random interval after natural exposure to these bacterial polysaccharide antigens are related to levels of IgG2 subclass, but antibody increases after vaccination appear to be affected more by other factors.

Interpretation of children's blood pressure using a physiologic height correction.

In a cross-sectional survey of 1834 black, Atlanta schoolchildren we corrected the customary blood pressure (BP) observations for the height of the arterial column extending from the BP cuff to the top (vertex) of the subject's head. Each cuff-to-vertex height was converted to its pressure equivalent in mmHg; then this pressure was subtracted from the observed BP to compute vertex-corrected BP values. The vertex-corrected mean arterial pressure (VMAP) ranged from 22.3 to 83.2 mmHg, but there was no estimated linear association between VMAP and age. For males, mean VMAP was 49.4 mmHg for ages 6-13 and 46.0 mmHg for ages 14-17. For females, mean VMAP was 50.2 mmHg for ages 6-17. Since VMAP appears to be independent of age in most of childhood, its use may simplify the development of pediatric BP reference values. VMAP can also serve as a non-invasive approximation of cerebral perfusion pressure. Investigators of primary hypertension may wish to use VMAP for comparing average BP levels between childhood groups which differ by potentially etiologic characteristics.