Effect of growth hormone treatment on adult height of children with idiopathic short stature. Genentech Collaborative Group.
BACKGROUND: Short-term administration of growth hormone to children with idiopathic short stature results in increases in growth rate and standard-deviation scores for height. However, the effect of long-term growth hormone therapy on adult height in these children is unknown. METHODS: We studied 121 children with idiopathic short stature, all of whom had an initial height below the third percentile, low growth rates, and maximal stimulated serum concentrations of growth hormone of at least 10 microg per liter. The children were treated with growth hormone (0.3 mg per kilogram of body weight per week) for 2 to 10 years. Eighty of these children have reached adult height, with a bone age of at least 16 years in the boys and at least 14 years in the girls, and pubertal stage 4 or 5. The difference between the predicted adult height before treatment and achieved adult height was compared with the corresponding difference in three untreated normal or short-statured control groups. RESULTS: In the 80 children who have reached adult height, growth hormone treatment increased the mean standard-deviation score for height (number of standard deviations from the mean height for chronologic age) from -2.7 to -1.4. The mean (+/-SD) difference between predicted adult height before treatment and achieved adult height was +5.0+/-5.1 cm for boys and +5.9+/-5.2 cm for girls. The difference between predicted and achieved adult height among treated boys was 9.2 cm greater than the corresponding difference among untreated boys with initial standard-deviation scores of less than -2, and the difference among treated girls was 5.7 cm greater than the difference among untreated girls. CONCLUSION: Long-term administration of growth hormone to children with idiopathic short stature can increase adult height to a level above the predicted adult height and above the adult height of untreated historical control children. (+info)
Capture-recapture models including covariate effects.
Capture-recapture methods are used to estimate the incidence of a disease, using a multiple-source registry. Usually, log-linear methods are used to estimate population size, assuming that not all sources of notification are dependent. Where there are categorical covariates, a stratified analysis can be performed. The multinomial logit model has occasionally been used. In this paper, the authors compare log-linear and logit models with and without covariates, and use simulated data to compare estimates from different models. The crude estimate of population size is biased when the sources are not independent. Analyses adjusting for covariates produce less biased estimates. In the absence of covariates, or where all covariates are categorical, the log-linear model and the logit model are equivalent. The log-linear model cannot include continuous variables. To minimize potential bias in estimating incidence, covariates should be included in the design and analysis of multiple-source disease registries. (+info)
The impact of a multidisciplinary approach on caring for ventilator-dependent patients.
OBJECTIVE: To determine the clinical and financial outcomes of a highly structured multidisciplinary care model for patients in an intensive care unit (ICU) who require prolonged mechanical ventilation. The structured model outcomes (protocol group) are compared with the preprotocol outcomes. DESIGN: Descriptive study with financial analysis. SETTING: A twelve-bed medical-surgical ICU in a non-teaching tertiary referral center in Ogden, Utah. STUDY PARTICIPANTS: During a 54 month period, 469 consecutive intensive care patients requiring mechanical ventilation for longer than 72 hours who did not meet exclusion criteria were studied. INTERVENTIONS: A multidisciplinary team was formed to coordinate the care of ventilator-dependent patients. Care was integrated by daily collaborative bedside rounds, monthly meetings, and implementation of numerous guidelines and protocols. Patients were followed from the time of ICU admission until the day of hospital discharge. MAIN OUTCOME MEASURES: Patients were assigned APACHE II scores on admission to the ICU, and were divided into eight diagnostic categories. ICU length of stay, hospital length of stay, costs, charges, reimbursement, and in-hospital mortality were measured. RESULTS: Mortality in the preprotocol and protocol group, after adjustment for APACHE II scores, remained statistically unchanged (21-23%). After we implemented the new care model, we demonstrated significant decreases in the mean survivor's ICU length of stay (19.8 days to 14.7 days, P= 0.001), hospital length of stay (34.6 days to 25.9 days, P=0.001), charges (US$102500 to US$78500, P=0.001), and costs (US$71900 to US$58000, P=0.001). CONCLUSIONS: Implementation of a structured multidisciplinary care model to care for a heterogeneous population of ventilator-dependent ICU patients was associated with significant reductions in ICU and hospital lengths of stay, charges, and costs. Mortality rates were unaffected. (+info)
Nonlinear tension summation of different combinations of motor units in the anesthetized cat peroneus longus muscle.
The purpose of this study was to examine the linearity of summation of the forces produced by the stimulation of different combinations of type identified motor units (MUs) in the cat peroneus longus muscle (PL) under isometric conditions. The muscle was fixed at its twitch optimal length, and the tension produced by the single MU was recorded during 24- and 72-Hz stimulation. The summation analysis was first carried out for MUs belonging to the same functional group, and then different combinations of fast fatigable (FF) MUs were added to the nonfatigable slow (S) and fatigue resistant (FR) group. The tension resulting from the combined stimulation of increasing numbers of MUs (measured tension) was evaluated and compared with the linearly predicted value, calculated by adding algebraically the tension produced by the individual MUs assembled in the combination (calculated tension). Tension summation displayed deviations from linearity. S and FR MUs mainly showed marked more than linear summation; FF MUs yielded either more or less than linear summation; and, when the FF units were recruited after the S and FR MUs, less than linear summation always occurred. The magnitude of the nonlinear summation appeared stimulus frequency dependent for the fatigable FF and FI group. The relationship between measured tension and calculated tension for each MU combination was examined, and linear regression lines were fitted to each set of data. The high correlation coefficients and the different slope values for the different MU-type combinations suggested that the nonlinear summation was MU-type specific. The mechanisms of nonlinear summations are discussed by considering the consequences of internal shortening and thus the mechanical interactions among MUs and shifts in muscle fiber length to a more or less advantageous portion of single MU length-tension curves. (+info)
Short-latency vergence eye movements induced by radial optic flow in humans: dependence on ambient vergence level.
Radial patterns of optic flow, such as those experienced by moving observers who look in the direction of heading, evoke vergence eye movements at short latency. We have investigated the dependence of these responses on the ambient vergence level. Human subjects faced a large tangent screen onto which two identical random-dot patterns were back-projected. A system of crossed polarizers ensured that each eye saw only one of the patterns, with mirror galvanometers to control the horizontal positions of the images and hence the vergence angle between the two eyes. After converging the subject's eyes at one of several distances ranging from 16.7 cm to infinity, both patterns were replaced with new ones (using a system of shutters and two additional projectors) so as to simulate the radial flow associated with a sudden 4% change in viewing distance with the focus of expansion/contraction imaged in or very near both foveas. Radial-flow steps induced transient vergence at latencies of 80-100 ms, expansions causing increases in convergence and contractions the converse. Based on the change in vergence 90-140 ms after the onset of the steps, responses were proportional to the preexisting vergence angle (and hence would be expected to be inversely proportional to viewing distance under normal conditions). We suggest that this property assists the observer who wants to fixate ahead while passing through a visually cluttered area (e.g., a forest) and so wants to avoid making vergence responses to the optic flow created by the nearby objects in the periphery. (+info)
Survival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers.
BACKGROUND: Studies of survival following breast and ovarian cancers in BRCA1 and/or BRCA2 mutation carriers have yielded conflicting results. We undertook an analysis of a community-based study of Ashkenazi Jews to investigate the effect of three founder mutations in BRCA1 and BRCA2 on survival among patients with breast or ovarian cancer. METHODS: We collected blood samples and questionnaire data from 5318 Ashkenazi Jewish volunteers. The blood samples were tested for 185delAG (two nucleotide deletion) and 5382insC (single nucleotide insertion) mutations in BRCA1 and the 6174delT (single nucleotide deletion) mutation in BRCA2. To estimate survival differences in the affected relatives according to their BRCA1 and/or BRCA2 mutation carrier status, we devised and applied a novel extension of the kin-cohort method. RESULTS: Fifty mutation carriers reported that 58 of their first-degree relatives had been diagnosed with breast cancer and 10 with ovarian cancer; 907 noncarriers reported 979 first-degree relatives with breast cancer and 116 with ovarian cancer. Kaplan-Meier estimates of median survival after breast cancer were 16 years (95% confidence interval [CI] = 11-40) in the relatives of carriers and 18 years (95% CI = 15-22) in the relatives of noncarriers, a difference that was not statistically significant (two-sided P = .87). There was also no difference in survival times among the 126 first-degree relatives with ovarian cancer. We found no survival difference between patients with breast or ovarian cancer who were inferred carriers of BRCA1 and/or BRCA2 mutations and noncarriers. CONCLUSIONS: Carriers of BRCA1 and BRCA2 mutations appeared to have neither better nor worse survival prognosis. (+info)
Long-term results of GH therapy in GH-deficient children treated before 1 year of age.
OBJECTIVES: To evaluate the long-term effects of GH therapy in early diagnosed GH-deficient patients treated before 1 year of age. STUDY DESIGN: We studied all 59 patients (33 males) recorded by Association France-Hypophyse and treated with GH (0.50+/-0.15 IU/kg (S.D.) per week) before 1 year of age. Clinical presentation and growth parameters under GH treatment were analyzed. RESULTS: Neonatal manifestations of hypopituitarism were frequent: hypoglycemia (n=50), jaundice (n=25) and micropenis (n=17/33). Although birth length was moderately reduced (-0.9+/-1.4), growth retardation at diagnosis (5.8+/-3.8 months) was severe (-3.5+/-1.9 standard deviation scores (SDS)). Fifty patients (85%) had thyrotropin and/or corticotropin deficiency. After a mean duration of GH therapy of 8.0+/-3.6 years, change in height SDS was +3.11+/-2.06 S.D., exceeding 4 SDS in 19 patients. Only 9 patients (15%) did not reach a height of -2 S.D. for chronological age and 20 patients (34%) exceeded their target height. Pretreatment height SDS was independently associated with total catch-up growth. CONCLUSION: Conventional doses of GH allow normalization of height in patients with early GH deficiency and treatment. (+info)
Changes in body composition and leptin levels during growth hormone (GH) treatment in short children with various GH secretory capacities.
OBJECTIVE: The aim of this study was to follow changes in body composition, estimated by dual-energy X-ray absorptiometry (DXA), in relation to changes in leptin during the first year of GH therapy in order to test the hypothesis that leptin is a metabolic signal involved in the regulation of GH secretion in children. DESIGN AND METHODS: In total, 33 prepubertal children were investigated. Their mean (S.D.) chronological age at the start of GH treatment was 11.5 (1.6) years, and their mean height was -2.33 (0.38) S.D. scores (SDS). GH was administered subcutaneously at a daily dose of 0.1 (n=26) or 0.2 (n=7) IU/kg body weight. Ten children were in the Swedish National Registry for children with GH deficiency, and twenty-three children were involved in trials of GH treatment for idiopathic short stature. Spontaneous 24-h GH secretion was studied in 32 of the children. In the 24-h GH profiles, the maximum level of GH was determined and the secretion rate estimated by deconvolution analysis (GHt). Serum leptin levels were measured at the start of GH treatment and after 10 and 30 days and 3, 6 and 12 months of treatment. Body composition measurements, by DXA, were performed at baseline and 12 months after the onset of GH treatment. RESULTS: After 12 months of GH treatment, mean height increased from -2.33 to -1.73 SDS and total body fat decreased significantly by 3.0 (3.3)%. Serum leptin levels were decreased significantly at all time points studied compared with baseline. There was a significant correlation between the change in total body fat and the change in serum leptin levels during the 12 months of GH treatment, whereas the leptin concentration per unit fat mass did not change. In a multiple stepwise linear regression analysis with 12 month change in leptin levels as the dependent variable, the percentage change in fat over 12 months, the baseline fat mass (%) of body mass and GHt accounted for 24.0%, 11.5% and 12.2% of the variability respectively. CONCLUSIONS: There are significant correlations between changes in leptin and fat and endogenous GH secretion in short children with various GH secretory capacities. Leptin may be the messenger by which the adipose tissue affects hypothalamic regulation of GH secretion. (+info)