Yersinia enterocolitica infections associated with improperly pasteurized milk products: southwest Pennsylvania, March-August, 2011.

In July 2011, a cluster of Yersinia enterocolitica infections was detected in southwestern Pennsylvania, USA. We investigated the outbreak's source and scope in order to prevent further transmission. Twenty-two persons were diagnosed with yersiniosis; 16 of whom reported consuming pasteurized dairy products from dairy A. Pasteurized milk and food samples were collected from this dairy. Y. enterocolitica was isolated from two products. Isolates from both food samples and available clinical isolates from nine dairy A consumers were indistinguishable by pulsed-field gel electrophoresis. Environmental and microbiological investigations were performed at dairy A and pasteurization deficiencies were noted. Because consumption of pasteurized milk is common and outbreaks have the potential to become large, public health interventions such as consumer advisories or closure of the dairy must be implemented quickly to prevent additional cases if epidemiological or laboratory evidence implicates pasteurized milk as the outbreak source.

Laboratory constraints on chameleon dark energy and power-law fields.

We report results from a search for chameleon particles created via photon-chameleon oscillations within a magnetic field. This experiment is sensitive to a wide class of unexplored chameleon power-law and dark energy models. These results exclude 5 orders of magnitude in the coupling of chameleons to photons covering a range of 4 orders of magnitude in chameleon effective mass and, for individual models, exclude between 4 and 12 orders of magnitude in chameleon couplings to matter.

Gonadal effects of vasectomy and vasoligation.

During a 28-week study, vasectomy and vasoligation of immature male Wistar rats revealed that there was a significant decrease in urinary 17-ketosteroid in the vasectomized group at week 15; at week 28 there were significant decreases in the weights of the testes of the test groups, as compared to those receiving sham operations, with maximum alterations in the vasectomized rats. Small, soft discolored testes with cysts in the cauda epididymis and vas deferens regions occurred frequently in the test groups. The output of 17-ketosteroid in the urine and the findings in the testes indicate significant alterations in the morphology and function of the testes and suggest the need for caution and extensive investigations in man before recommending vasectomy as a simple, innocuous, "physiologic" means to ensure conception control.

Self-limited febrile syndromes temporally associated with the use of propofol for sedation in gastrointestinal endoscopic procedures.

PURPOSE: To investigate cases of febrile illnesses in patients who received propofol for sedation during gastrointestinal endoscopy. METHODS: Active case finding for patients who underwent endoscopy between 1 April and 30 May 2007 and suffered unexplained fever, chills, or myalgia within 48 hour after the procedure. We reviewed medications and clinical practices to find factors associated with the reactions. RESULTS: Seventy-four cases at eight facilities in five states were identified yielding a rate of 36 reactions per 1000 procedures, compared with a baseline rate of 0.6 per 1000. The majority of patients experienced self-limited fever (89.2%), chills (73.0%), or myalgia (63.5%). Blood samples from five patients were collected for culture; no organisms grew. All health care facilities that reported cases and fully participated in the investigation (n = 7) had received a common lot of propofol just before recognition of the first case. Bacterial endotoxin and sterility testing on unopened vials from this lot of propofol showed no abnormalities. Cases terminated after facilities stopped using the associated lot of propofol. CONCLUSIONS: We found a temporal association between a particular lot of propofol and an outbreak of febrile illnesses at several healthcare facilities performing endoscopy. When propofol is used to sedate patients for endoscopy, fever is a rare outcome and healthcare professionals should investigate clusters of these reactions. Post-procedure surveillance is important to identify possible medication reactions.

Post-combat adaptation: improving social support and reaching constructive growth.

BACKGROUND AND OBJECTIVES: Posttraumatic stress disorder, a commonly researched mental health outcome associated with trauma, does not develop in the majority of survivors. More common trajectories of adaptation include resilience, and posttraumatic growth (PTG). The objectives of the current study were to: (1) describe posttrauma adaptation profiles in a sample of Israeli male military veterans (N = 448); and (2) to explore the protective factors that promote constructive PTG within two profiles of posttrauma adaptation. METHODS: The study used secondary data to estimate latent profile mixture models and a series of logistic regression analyses. RESULTS: Demographic controls, combat related variables, endorsement of coping strategies, and reports of improvement in social support were not significant predictors of constructive growth in the resilient class. However, those in the struggling growth subset of the sample who reported improvement in perceived social support increased the odds of reaching constructive growth. CONCLUSION: These findings highlight the importance of tailored clinical interventions that account for more complex profiles of posttrauma adaptation; and further, provide evidence that adaptation takes place over time. Finally, these findings call for future research to continue to explore the quality of PTG and the contexts in which protective factors promote positive adaptation.

Physical deconditioning is the common denominator in both obese and overweight subjects with nonalcoholic steatohepatitis.

BACKGROUND: Obesity and decreased physical activity mirror increasing prevalence of nonalcoholic fatty liver disease (NAFLD). AIM: We aimed to investigate associations between aerobic fitness, anthropometrics and disease parameters in patients with nonalcoholic steatohepatitis (NASH). We hypothesised that NASH subjects have lower aerobic power and capacity than untrained, sedentary, normal subjects. METHODS: Forty subjects (60% obese, 40% overweight) with biopsy-confirmed NASH and NAFLD activity score (NAS) ≥4 were enrolled in a clinical trial where anthropometrics, laboratories, liver fat content by MRI, activity, and aerobic fitness by cycle ergometry data were obtained. RESULTS: NASH subjects were significantly deconditioned compared to 148 untrained, sedentary, healthy subjects from our laboratory in aerobic power (VO2peak) (NASH 16.8 ± 6.6 vs control 28.4 ± 10.6 mL/kg/min, P < 0.0001) and capacity (VO2 at lactate threshold [LT]) (NASH 8.3 ± 2.5 vs control 14.1 ± 5.9 mL/kg/min, P < 0.0001). NASH subjects' fitness was comparable to the "least fit" tertile of controls: VO2peak [NASH 16.8 ± 6.6 vs "least fit" 17.3 ± 3.3, P = 0.64]) and VO2 at LT (NASH 8.3 ± 2.5 vs "least fit" 9.3 ± 2.1, P = 0.31). Fitness was similar in obese compared to overweight subjects (adjusted for gender) and was not correlated with visceral adiposity or NAS. Engaging in dedicated cardiovascular activity correlated with higher VO2peak and VO2peak at LT. CONCLUSIONS: Aerobic deconditioning was universally present in NASH subjects. NASH subjects' fitness was similar to our laboratory's "least fit" untrained, sedentary control subjects. Further research investigating NASH patients' ability to improve low baseline aerobic fitness is warranted.

Tuberculosis susceptibility patterns, predictors of multidrug resistance, and implications for initial therapeutic regimens at a New York City hospital.

BACKGROUND: Multidrug resistance has complicated tuberculosis therapy. We studied antibiotic susceptibilities of Mycobacterium tuberculosis and predictors of multidrug resistance to assist in determining initial drug regimens. METHODS: We conducted a case-control study based on chart review of patients with and without multidrug-resistant tuberculosis, including outpatients and inpatients with culture-proved tuberculosis seen at a large New York, NY, hospital during 1991 and 1992. Patient characteristics studied included serologic findings for human immunodeficiency virus and the presence of the acquired immunodeficiency syndrome. Descriptive analysis considered potential initial drug regimens. A theoretically effective regimen was assumed to contain at least two drugs to which an isolate was susceptible. RESULTS: For 172 patients, 28.5% of isolates were resistant to isoniazid, at least 20.9% to rifampin, 15.7% to ethambutol, 8.1% to pyrazinamide, 18.6% to streptomycin, 9.9% to ethionamide, 8.1% to kanamycin, and none to capreomycin, cycloserine, and ciprofloxacin; 18.6% were resistant to both isoniazid and rifampin. Chart review of 159 patients showed that acquired immunodeficiency syndrome, human immunodeficiency virus seropositivity, female gender, residence in the Bronx, and race were associated with multidrug resistance. The four-drug regimen of isoniazid, rifampin, ethambutol, and pyrazinamide was theoretically effective for 81% to 85% of patients. No subset of patients would have a markedly better theoretical benefit from that regimen. Only five- or six-drug regimens that used the combinations of capreomycin plus ciprofloxacin, capreomycin plus cycloserine, ciprofloxacin plus cycloserine, or all three drugs together theoretically offered significantly higher effectiveness. CONCLUSIONS: Tuberculosis isolates at our hospital have a high frequency of multidrug resistance. Only five- or six-drug regimens are theoretically adequate as initial therapy for our patients.

E2 supplementation selectively relieves GH's autonegative feedback on GH-releasing peptide-2-stimulated GH secretion.

Female gender confers resistance to GH autonegative feedback in the adult rat, thereby suggesting gonadal or estrogenic modulation of autoregulation of the somatotropic axis. Here we test the clinical hypothesis that short-term E2 replacement in ovariprival women reduces GH's repression of spontaneous, GHRH-, and GH-releasing peptide (GHRP)-stimulated GH secretion. To this end, we appraised GH autoinhibition in nine healthy postmenopausal volunteers during a prospective, randomly ordered supplementation with placebo vs. E [1 mg micronized 17 beta-E2 orally twice daily for 6-23 d]. The GH autofeedback paradigm consisted of a 6-min pulsed i.v. infusion of recombinant human GH (10 microg/kg square-wave injection) or saline (control) followed by i.v. bolus GHRH (1 microg/kg), GHRP-2 (1 microg/kg), or saline 2 h later. Blood was sampled every 10 min and serum GH concentrations were measured by chemiluminescence. Poststimulus GH release was quantitated by multiparameter deconvolution analysis using published biexponential kinetics and by the incremental peak serum GH concentration response (maximal poststimulus value minus prepeak nadir). Outcomes were analyzed on the logarithmic scale by mixed-effects ANOVA at a multiple-comparison type I error rate of 0.05. E2 supplementation increased the (mean +/- SEM) serum E2 concentration from 43 +/- 1.8 (control) to 121 +/- 4 pg/ml (E2) (158 +/- 6.6 to 440 +/- 15 pmol/liter; P < 0.001), lowered the 0800 h (preinfusion) serum IGF-I concentration from 127 +/- 7.7 to 73 +/- 3.6 microg/liter (P < 0.01), and amplified spontaneous pulsatile GH production from 7.5 +/- 1.1 to 13 +/- 2.3 microg/liter per 6 h (P = 0.020). In the absence of exogenously imposed GH autofeedback, E2 replacement enhanced the stimulatory effect of GHRP-2 on incremental peak GH release by 1.58-fold [95% confidence interval, 1.2- to 2.1-fold] (P = 0.0034) but did not alter the action of GHRH (0.83-fold [0.62- to 1.1-fold]). In the E2-deficient state, bolus GH infusion significantly inhibited subsequent spontaneous, GHRH-, and GHRP-induced incremental peak GH responses by, respectively, 33% (1-55%; P = 0.044 vs. saline), 79% (68-86%; P < 0.0001), and 54% (32-69%; P = 0.0002). E2 repletion failed to influence GH autofeedback on either spontaneous or GHRH-stimulated incremental peak GH output. In contrast, E2 replenishment augmented the GHRP-2-stimulated incremental peak GH response in the face of GH autoinhibition by 1.7-fold (1.2- to 2.5-fold; P = 0.009). Mechanistically, the latter effect of E2 mirrored its enhancement of GH-repressed/GHRP-2-stimulated GH secretory pulse mass, which rose by 1.5-fold (0.95- to 2.5-fold over placebo; P = 0.078). In summary, the present clinical investigation documents the ability of short-term oral E2 supplementation in postmenopausal women to selectively rescue GHRP-2 (but not spontaneous or GHRH)-stimulated GH secretion from autonegative feedback. The secretagogue specificity of E's relief of GH autoinhibition suggests that this sex steroid may enhance activity of the hypothalamopituitary GHRP-receptor/effector pathway.

Cortisol and growth hormone responses to exercise at different times of day.

Exercise of appropriate intensity is a potent stimulus for GH and cortisol secretion. Circadian and diurnal rhythms may modulate the GH and cortisol responses to exercise, but nutrition, sleep, prior exercise patterns, and body composition are potentially confounding factors. To determine the influence of the time of day on the GH and cortisol response to acute exercise, we studied 10 moderately trained young men (24.1 +/- 1.1 yr old; maximal oxygen consumption, 47.9 +/- 1.4 mL/kg.min; percent body fat, 13.2 +/- 0.6%). After a supervised night of sleep and a standard meal 12 h before exercise, subjects exercised at a constant velocity (to elicit an initial blood lactate concentration of approximately 2.5 mmol/L) on a treadmill for 30 min on 3 separate occasions, starting at 0700, 1900, and 2400 h. Blood samples were obtained at 5-min intervals for 1 h before and 5 h after the start of exercise; subjects were not allowed to sleep during this period. Subjects were also studied on 3 control days under identical conditions without exercise. There were no significant differences with time of day in the mean blood lactate and submaximal oxygen consumption values during exercise. The differences over time in serum GH and cortisol concentrations between the exercise day and the control day were determined with 95% confidence limits for each time of day. Exercise stimulated a significant increase in serum GH concentrations over control day values for approximately 105--145 min (P < 0.05) with no significant difference in the magnitude of this response by time of day. The increase in serum GH concentrations with exercise was followed by a transient suppression of GH release (for approximately 55--90 min; P < 0.05) after exercise at 0700 and 1900 h, but not at 2400 h. Although the duration of the increase in serum cortisol concentrations after exercise was similar (approximately 150--155 min; P < 0.05) at 0700, 1900, and 2400 h, the magnitude of this increase over control day levels was greatest at 2400 h. This difference was significant for approximately 130 min and approximately 40 min compared to exercise at 1900 and 0700 h, respectively (P < 0.05). The cortisol response to exercise at 0700 h was significantly greater than that at 1900 h for about 55 min (P < 0.05). A rebound suppression of cortisol release for about 50 min (P < 0.05) was observed after exercise at 2400 h, but not 0700 or 1900 h. Both baseline (before exercise) and peak cortisol concentrations were significantly higher at 0700 h than at 1900 or 2400 h (P < 0.01). We conclude that time of day does not alter the GH response to exercise; however, the exercise-induced cortisol response is modulated by time of day.

Short-term modulation of the androgen milieu alters pulsatile, but not exercise- or growth hormone (GH)-releasing hormone-stimulated GH secretion in healthy men: impact of gonadal steroid and GH secretory changes on metabolic outcomes.

Gonadal steroids are known to alter GH secretion as well as tissue metabolism. The present study was designed to examine the effects of short term (2- to 3-week) alterations in gonadal steroids on basal pulsatile (nonstimulated) and exercise- and GH-releasing hormone-stimulated GH secretion, urinary nitrogen excretion, and basal and exercise-stimulated oxygen consumption. Two protocols were conducted, which reflect a total of 18 separate studies. In the first paradigm, 5 healthy young men were each studied in a double blind, randomized manner during 3 different gonadal hormone manipulations, in which serum testosterone was varied from hypogonadal (induced by leuprolide) to eugonadal (saline injections) to high levels (testosterone enanthate, 3 mg/kg.week, i.m.). There was a washout period of 8 weeks between treatments. In the second protocol, 3 of the original subjects were studied after 2 weeks of treatment with stanozolol (0.1 mg/kg.day). Two to 3 weeks after the desired changes in serum testosterone, each subject was admitted to the General Clinical Research Center for study. The hypogonadal state (serum testosterone, 33 ng/dL) increased urinary nitrogen loss (by 34%; P < 0.005) and decreased basal metabolic rate (by 12%; P < 0.02) compared with the eugonadal state (testosterone, 796 ng/dL). High dose testosterone (1609 ng/dL) further decreased urinary nitrogen loss over the eugonadal state (by 16%; P < 0.05). Stanozolol yielded the lowest urinary nitrogen excretion of all (P < 0.03). Like urinary nitrogen, the basal metabolic rate showed the greatest change between the hypogonadal and eugonadal states (12%; P < 0.02), with a lesser change during high dose testosterone treatment (4%). Analogously, end-exercise oxygen consumption rose by 11% between the hypogonadal and eugonadal states (P < 0.05). Between the hypogonadal and eugonadal states, no significant changes in pulsatile (nonstimulated), exercise-stimulated, or GRF-stimulated GH secretion or serum insulin-like growth factor I concentrations were observed. Raising testosterone to supraphysiological levels increased pulsatile GH secretion by 62% over that with leuprolide and by 22% over that with saline (P < 0.05). High dose testosterone treatment also increased serum insulin-like growth factor I concentrations by 21% and 34% over those during the eugonadal and hypogonadal states, respectively (P < 0.01). Testosterone did not affect either exercise- or GRF-stimulated GH secretion. In protocol 2, stanozolol did not affect any parameter of GH secretion. To examine the interaction between GH secretion and testosterone on urinary nitrogen excretion and basal metabolic rate, a one-way analysis of covariance was undertaken. Statistical examination of GH production as the covariate and testosterone (by tertile) as the interactive factor demonstrated significant relationships between serum testosterone levels and either urinary nitrogen (P < 0.02) or basal metabolic rate (P < 0.01), but not GH secretion (P = NS). In summary, these results demonstrate that short term modulation of the androgen milieu affects metabolic outcome without necessitating changes in GH secretion. These results have significance for both normal physiology and for the treatment of hypogonadal GH-deficient patients.

Reliability of estimates of pulsatile characteristics of luteinizing hormone and growth hormone release in women.

The test-retest reliability of estimates of pulsatile LH and GH release was evaluated in 23 eumenorrheic women during the early follicular phase of the menstrual cycle. Each subject was studied during two successive or near-successive menstrual cycles by repetitive blood sampling every 10 min for 24 h. Pulsatile parameters for LH and GH release were identified and characterized using the Cluster pulse detection algorithm. For LH, no significant differences existed in any parameter mean between the two 24-h admissions. Correlation coefficients for consecutive 24-h studies ranged from r = 0.22 (P less than 0.32) for number of LH peaks to r = 0.79 (P less than 0.0001) for 24-h integrated LH values (area under the concentration vs. time curve). No significant mean differences in any parameter were observed for consecutive 24-h GH evaluations. Correlation coefficients for 24-h GH ranged from r = 0.25 (P less than 0.34) for nadir to r = 0.71 (P less than 0.002) for incremental peak increase. Cosinor analysis was used to determine significant 24-h variations in LH and GH concentrations. Statistically significant differences existed between admissions for the amplitude of the nyctohemeral LH rhythm and its acrophase (time at which maximal hormone value was attained), but no mean differences were found for mesor (mean concentration). Correlation coefficients for LH were r = 0.10 (P less than 0.65), r = 0.43 (P less than 0.08), and r = 0.78 (P less than 0.0001) for phase, amplitude, and mesor, respectively. No significant mean differences existed for any parameter of nyctohemeral GH rhythms. Correlation coefficients were r = -0.18 (P less than 0.52), r = 0.49 (P less than 0.72), and r = 0.14 (P less than 0.80) for 24-h GH amplitude, phase, and mesor, respectively. We conclude that comparisons of mean and integrated LH and GH concentrations over a 24-h interval in the early follicular phase of the menstrual cycle are reliable; however, certain pulsatile properties responsible for the achievement of the mean daily concentrations of LH and GH may be nonuniform from menstrual cycle to menstrual cycle. In addition, nonuniformities may exist in the nyctohemeral rhythms of serum concentrations of LH and GH in the adult woman between cycles when a single 24-h time series is the basis for the analysis.

Relationship between age, percentage body fat, fitness, and 24-hour growth hormone release in healthy young adults: effects of gender.

We investigated whether gender affects the physiological relationships between the release of GH and age, body composition, and levels of physical fitness in humans. We studied 32 eumenorrheic females (age = 31 +/- 5 yr) and 12 males (age = 27 +/- 5 yr). Significant gender differences were found for peak oxygen consumption [VO2 peak = 40.5 +/- 6.9 (females) vs. 50.1 +/- 11.6 (males) ml/kg.min-1, P < 0.05] and body composition [hydrostatic weighing, percentage body fat = 28.7 +/- 5.4 (females) vs. 18.1 +/- 9.8 (males), P < 0.05] but not for body mass index [BMI = 23.7 +/- 3.1 (females) vs. 24.0 +/- 3.3 (males)]. Blood samples were drawn every 10 min for 24 h from 0800 h to determine integrated serum GH concentration [2350 +/- 1260 (females) vs. 3110 +/- 1760 (males) microgram/L x min]; females were studied during the early follicular phase (days 4-5) of the menstrual cycle. In females, a significant relationship existed between 24-h integrated serum GH concentration and age (r = -0.35, P = 0.05) but not BMI (r = -0.19, P = 0.29); the relationship between 24-h integrated serum GH concentration and VO2 peak (r = 0.31, P = 0.08) and percentage body fat (r = 0.29, P = 0.11) approached significance. In males, significant relationships existed between 24-h integrated serum GH concentration and age (r = -0.79, P = 0.002), percentage body fat (r = -0.75, P = 0.005), and VO2 peak (r = 0.58, P = 0.05) but not between 24-h integrated serum GH concentration and BMI (r = -0.53, P = 0.08). Standardized regression coefficients revealed that for each SD change in age, BMI, percentage body fat, or VO2 peak the associated change in 24-h integrated serum GH concentration was 1.9-2.6 times greater in males than in females. We conclude that age, percentage body fat (but not BMI), and fitness are related to 24-h GH release in young adults and that these relationships are considerably stronger in males than females.

Alterations in growth and body composition during puberty: III. Influence of maturation, gender, body composition, fat distribution, aerobic fitness, and energy expenditure on nocturnal growth hormone release.

We examined the relationships among gender, sexual maturation, four-compartment model estimates of body composition, body fat distribution (magnetic resonance imaging for abdominal visceral fat and anthropometrics), aerobic fitness, basal and total energy expenditure, and overnight GH release in an ultrasensitive chemiluminescence assay in healthy prepubertal and pubertal boys (n = 18 and 11, respectively) and girls (n = 12 and 18, respectively). Blood samples were withdrawn every 10 min from 1800-0600 h to determine the area under the serum GH-time curve (AUC), sum of the GH peak heights (sigma GH peak heights), and the mean nadir GH concentration. GH release was greater in the pubertal than prepubertal subjects due to an increase in sigma GH peak heights (43.8 +/- 3.6 vs. 24.1 +/- 3.5 ng.mL-1, P = 0.0002) and mean nadir (1.7 +/- 0.2 vs. 0.7 +/- 0.2 ng.mL-1, P = 0.0002), but not peak number (4.3 +/- 0.2 vs. 4.5 +/- 0.2). The girls had a greater sigma GH peak heights (39.0 +/- 3.5 vs. 28.8 +/- 3.6 ng.mL-1, P = 0.05) and mean nadir concentration (1.4 +/- 0.2 vs. 0.9 +/- 0.2 ng.mL-1, P = 0.05) than the boys. Significant inverse relationships existed between sigma GH peak heights (r = -0.35, P = 0.06) or mean nadir (r = -0.39, P = 0.04) and four-compartment percent body fat for all boys but not for all girls or when combining all subjects. For all girls, significant inverse relationships existed between sigma GH peak heights (r = -0.39, P = 0.03) or mean nadir (r = -0.37, P = 0.04) and waist/hip ratio. Similar inverse relationships in all boys or all subjects were not significant. Forward stepwise regression analysis determined that bone age (i.e. maturation, primary factor) and gender were the significant predictors of AUC, sigma GH peak heights, and mean nadir. The influence of maturation reflects rising sex steroid concentrations, and the gender differences appear to be because of differences in estradiol concentrations rather than to body composition or body fat distribution.

Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay.

A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in men. However, how age, sex steroid hormones, and obesity singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 microgram/L) and high sensitivity and specificity (> or = 90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese men, whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum insulin-like growth factor I (IGF-I), IGF-I-binding protein-1 (IGFBP-1), and IGFBP-3 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 micrograms/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = -0.610; P < 0.01). In contrast, testosterone was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum testosterone concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum testosterone (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum estradiol (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum estradiol (r = -0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex steroids. The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum IGF-I concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = -0.611; P = 0.009).(ABSTRACT TRUNCATED AT 400 WORDS)

Abdominal visceral fat and fasting insulin are important predictors of 24-hour GH release independent of age, gender, and other physiological factors.

Numerous physiological factors modulate GH secretion, but these variables are not independent of one another. We studied 40 younger (20-29 yr.; 21 men and 19 women) and 62 older (57-80 yr.; 35 men and 27 women) adults to determine the contributions of several demographic and physiological factors to the variability in integrated 24-h GH concentrations. Serum GH was measured every 10 min for 24 h in an enhanced sensitivity chemiluminescence assay. The predictor variables included: age group (young or old), gender, abdominal visceral fat (by computed tomography), total body fat mass and percentage body fat by dual-energy x-ray absorptiometry, serum IGF-I, fasting serum insulin, 24-h mean estradiol and testosterone, and peak oxygen uptake by graded exercise (treadmill) testing. Multiple ordinary least squares regression analysis was used to quantitatively assess the individual contribution that each predictive measure made to explain the variability among values of integrated 24-h GH concentrations while in the presence of the remaining predictors. The model explained 65% of the variance in integrated 24-h GH concentrations. Abdominal visceral fat (P < 0.002) and fasting insulin (P < 0.008) were consistently important predictors of integrated 24-h GH concentrations independent of age group, gender, and all other predictor variables. Although serum IGF-I was an important overall predictor of integrated 24-h GH concentrations (P = 0.002), this relationship was present only in the young subjects and was modulated by gender. The remaining variables failed to contribute significantly to the model. We conclude that abdominal visceral fat and fasting insulin are important predictors of integrated 24-h GH concentrations in healthy adults, independent of age and gender. Serum IGF-I is an important predictor of integrated 24-h GH concentrations in young but not older subjects. Bidirectional feedback between each of these three factors and GH secretion may account for the strong relationships observed.

Accurate assessment of body composition in obese females.

Although several generalized regression equations exist for body composition assessment the accuracy of these equations for special populations is uncertain. This study examined the ability to predict body composition variables from girth measurements in obese women. Girth measurements were taken on 156 obese women at abdomen 1 and abdomen 2 (mean value of the two was used), buttocks, and right thigh. Stepwise multiple-regression analysis generated on 110 randomly assigned subjects yielded the following equations: density (g/cc) = -0.00020(mean abdomen) - 0.00032(wt) + 0.00039(ht) + 0.97783 (R = 0.76, SEE = +/- 0.00061); % fat = 0.11077(mean abdomen) - 0.17666(ht) + 0.14354(wt) + 51.03301 (R = 0.76, SEE = +/- 2.9); fat wt (kg) = 0.62039(wt) - 0.17844(ht) + 0.09495(mean abdomen) + 5.88874 (R = 0.96, SEE = +/- 2.9); and lean body wt (kg) = 0.37939(wt) + 0.17898(ht) - 0.09494(mean abdomen) - 6.00423 (R = 0.89, SEE = +/- 3.0). Data from the remaining 46 women were used for cross-validation. These equations were valid, with validity coefficients for fat weight and lean body weight of r = 0.92 (SE = +/- 3.3 kg) and r = 0.86 (SE = +/- 3.3 kg), respectively, with no significant mean differences between actual and predicted values. The use of girth measurements is a simple and practical method of estimating fat weight and lean body weight in obese women.

Dietary patterns, eating behaviors, and bone mineral density in women runners.

Although reduced gonadal steroid hormone concentrations appear to play a major role in lower trabecular bone mineral density (BMD) in women with athletic amenorrhea, dietary deficiencies and eating behaviors may also affect BMD in women runners. To investigate this possibility, dietary patterns (7-d records), eating-disorders inventory (EDI), and BMD were examined in nine nonrunning eumenorrheic control (Contl) and 32 women runners classified as eumenorrheic (n = 19, Eumen) and oligo/amenorrheic (a group in which some were oligomenorrheic and some were amenorrheic; Ol/Am, n = 13). Runner groups had similar cardiorespiratory fitness, body composition, and training characteristics. Lumbar spine BMD was lower in the Ol/Am runners (-12%, P less than 0.05) but proximal femur BMD did not differ. Dietary intake and EDI subscale scores were similar among the groups. However, there was an inverse trend between EDI subscale scores for bulimia and ineffectiveness and femoral BMD in the Ol/Am runners (r = -0.62 to -0.71, P less than 0.05). These results suggest that self-reported dietary intake and/or eating behaviors do not predict reproductive-function alterations in women runners, but eating behaviors may be associated with lower BMD in Ol/Am runners.

Alterations in growth and body composition during puberty. IV. Energy intake estimated by the youth-adolescent food-frequency questionnaire: validation by the doubly labeled water method.

BACKGROUND: Estimates of energy intake are required for an understanding of growth and disease; however, few methods of energy intake in children have been validated. OBJECTIVE: Our objective was to validate energy intake estimated by the Youth-Adolescent Food-Frequency Questionnaire (YAQ) against the criterion total energy expenditure (TEE) by doubly labeled water (DLW). DESIGN: Twenty-three boys and 27 girls (8.6-16.2 y of age) completed the YAQ and TEE measurements in 1 y. RESULTS: Energy intake by the YAQ (10. 03 +/- 3.12 MJ) and energy expenditure by DLW (9.84 +/- 1.79 MJ) were similar (P: = 0.91) with large lower (-6.30 MJ) and upper (6.67 MJ) +/-2 SD limits of agreement. When within-subject CVs of repeated measures of the DLW and YAQ methods were used, 25 of the 50 subjects were deemed to have misreported their energy intake. The discrepancy in energy intake (YAQ - TEE) was related to body weight (r = -0.25, P: = 0.077) and percentage body fat (r = -0.24, P: = 0.09) but not to age (r = -0.07, P: = 0.63) or the time between measures. From logistic regression, fatter boys were more likely to underreport energy intake than were fatter girls. CONCLUSION: The YAQ provides an accurate estimation of mean energy intake for a group but not for an individual.

Long-term endurance training alters the hypothalamic-pituitary axes for gonadotropins and growth hormone.

In a prospective fashion we have studied the impact of chronic exercise of two intensities on the hypothalamic-pituitary-end organ axes for gonadotropins and GH in gynecologically mature, previously sedentary women. Physiologic alterations are evident in both axes with a doubling of 24-hour mean serum GH concentrations at 1 year and smaller, transient changes in pulsatile LH release during the first four menstrual cycles. The latter period of physiologic adaptation should be studied more intensively with more frequent exercise evaluation. Perhaps more significant "adaptation to stress" would be quantitated. We also emphasize that gynecologically less mature women were not studied and only the early follicular phase was evaluated. Adaptive changes of greater magnitude (including amenorrhea) might have been produced if a different group of women, a markedly different training regimen, or a different phase of the menstrual cycle were studied. Finally, whether or not they participate in physical training, younger amenorrheic women are at increased risk for diminished lumbar spine bone mineral content and skeletal fractures.

Unequal impact of age, percentage body fat, and serum testosterone concentrations on the somatotrophic, IGF-I, and IGF-binding protein responses to a three-day intravenous growth hormone-releasing hormone pulsatile infusion in men.

We here investigate the potential rescue of the relative hyposomatotropism of aging and obesity by 3-day pulsatile GHRH infusions (i.v. bolus 0.33 microg/kg every 90 min) in 19 healthy men of varying ages (18 to 66 years) and body compositions (12 to 37% total body fat). Baseline (control) and GHRH-driven pulsatile GH secretion (in randomly ordered sessions) were quantitated by deconvolution analysis of 24-h (10-min sampling) serum GH concentration profiles measured in an ultrasensitive (threshold 0.005 microg/l) chemiluminescence assay. GHRH infusion significantly increased the mean (24-h) serum GH concentration (0.3 +/- 0.1 basal vs 2.4 +/- 0.4 microg/l treatment; P = 0.0001), total daily pulsatile GH production rate (21 +/- 9.5 vs 97 +/- 17 microg/l/day; P = 0.01), GH secretory burst frequency (11 +/- 0.5 vs 17 +/- 0.3 events/day; P = <0.01), and mass of GH released per burst (1.1 +/- 0.4 vs 5.9 1 microg/l; P < 0.01), as well as serum IGF-I (261 +/- 33 vs 436 +/- 37 microg/l; P = 0.005), insulin (45 +/- 13 vs 79 +/- 17 mU/l; P = 0.0002), and IGF binding protein (IGFBP)-3 (3320 +/- 107 vs 4320 +/- 114 microg/l; P = 0.001) concentrations, while decreasing IGFBP-1 levels (16 +/- 1.2 vs 14 +/- 0.09 microg/l; P = 0.02). Serum total testosterone and estradiol concentrations did not change. GHRH treatment also reduced the half-duration of GH secretory bursts, and increased the GH half-life. GHRH-stimulated 24-h serum GH concentrations and the mass of GH secreted per burst were correlated negatively with age (R[value]:P[value] = -0.67:0.002 and -0.58:0.009 respectively), and percentage body fat (R:P = -0.80:0.0001 and -0.65:0.0005 respectively), but positively with serum testosterone concentrations (R:P = +0.55:0.016 and +0.53:0.019 respectively). GHRH-stimulated plasma IGF-I increments correlated negatively with age and body mass index, and positively with serum testosterone, but not with percentage body fat. Cosinor analysis disclosed persistent nyctohemeral rhythmicity of GH secretory burst mass (with significantly increased 24-h amplitude and mesor values) but unchanged acrophase during fixed pulsatile GHRH infusions, which suggests that both GHRH- and non-GHRH-dependent mechanisms can modulate the magnitude (but only non-GHRH mechanisms can modulate the timing) of somatotrope secretory activity differentially over a 24-h period. In summary, diminished GHRH action and/or non-GHRH-dependent mechanisms (e.g. somatostatin excess, putative endogenous growth hormone-releasing peptide deficiency etc.) probably underlie the hyposomatotropism of aging, (relative) obesity, and/or hypoandrogenemia. Preserved or increased tissue IGF-I responses to GHRH-stimulated GH secretion (albeit absolutely reduced, suggesting GHRH insensitivity in obesity) may distinguish the pathophysiology of adiposity-associated hyposomatotropism from that of healthy aging.