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Biomedical subjects

D L Waters

Publications and source records attributed to D L Waters.

At least 19 recordsLinked to original sources

Increased pulsatility, process irregularity, and nocturnal trough concentrations of growth hormone in amenorrheic compared to eumenorrheic athletes.

Amenorrheic athletes exhibit a spectrum of neuroendocrine disturbances, including alterations in the GH-insulin-like growth factor I (IGF-I) axis. Whether these changes are due to exercise or amenorrhea is incompletely characterized. The present study investigates spontaneous (overnight) and exercise-stimulated GH secretion and associated IGF-binding proteins (IGFBPs) in amenorrheic (AA; n = 5), and eumenorrheic athletes ( n = 5) matched for age, percent body fat (dual energy x-ray absorptiometry), training history, and maximal oxygen consumption. Each volunteer participated in two hospital admissions consisting of a 50-min submaximal exercise bout (70% maximal oxygen consumption) and an 8-h nocturnal sampling period. Deconvolution analysis of serum GH concentration time series revealed increases in the half-life of GH (60%) and the number of secretory bursts (85%) as well as a decrease in their half-duration (50%) and the mass of GH secreted per pulse (300%) in the AA cohort. Time occupancy at elevated trough GH concentrations was significantly increased, and GH pulsatility (approximate entropy) was more irregular in the AA group. During exercise, AA exhibited a reversal of the normal relationship between IGF-I and GH, and a 4- to 5-fold blunting of stimulated peak and integrated GH secretion. Fasting levels of plasma IGF-I, IGFBP-3, and IGFBP-1 appeared to be unaffected by menstrual status. In ensemble, this phenotype of GH release in amenorrheic athletes suggests disrupted neuroregulation of episodic GH secretion, possibly reflecting decreased somatostinergic inhibition basally, and reduced GHRH output in response to exercise compared with eumenorrheic athletes. Accordingly, we postulate that the amenorrheic state, beyond the exercise experience per se, alters the neuroendocrine control of GH output in amenorrheic athletes.

Adult↗

Sarcopenia: current perspectives.

The development of sarcopenia is a complex multi-factorial process which begins in mid-life and accelerates after the age of 75 years. Although exercise, nutritional supplementation, hormone replacement and pro-inflammatory cytokine therapy may improve health status and reduce mortality, a better understanding of the complex interactions between these factors are needed. This review will focus on current information regarding the roles that physical activity, hormonal changes, energy intake, oxidative stress, and inflammatory processes play on the development and progression of sarcopenia.

Adult↗

Predictors of skeletal muscle mass in elderly men and women.

BACKGROUND: Elderly men and women lose muscle mass and strength with increasing age. Decreased physical activity, hormones, malnutrition and chronic disease have been identified as factors contributing to this loss. There are few data, however, for their multivariate associations with muscle mass and strength. This study analyzes these associations in a cross-sectional sample of elderly people from the New Mexico Aging Process Study. METHODS: Data collected in 1994 for 121 male and 180 female volunteers aged 65-97 years of age enrolled in The New Mexico Aging Process Study were analyzed. Body composition was measured using dual energy X-ray absorptiometry; dietary intake from 3 day food records; usual physical activity by questionnaire; health status from annual physical examinations; and serum testosterone, estrone, sex-hormone binding globulin (SHBG), and insulin-like growth factor (IGF1) from radioimmunoassays of fasting blood samples. Statistical analyses included partial correlation and stepwise multiple regression. RESULTS: The muscle mass and strength (adjusted for knee height) decreased with increasing age in both sexes. The muscle mass was significantly associated with serum free-testosterone, physical activity, cardiovascular disease, and IGF1 in the men. In the women, the muscle mass was significantly associated with total fat mass and physical activity. Age was not associated significantly with muscle mass after controlling for these variables. Grip strength was associated with age independent of muscle mass in both sexes. Estrogen (endogenous and exogenous) was not associated with muscle mass or strength in women. CONCLUSIONS: Age-related loss of muscle mass and strength occurs in relatively healthy, well-nourished elderly men and women and has a multifactorial basis. Sex hormone status is an important factor in men but not in women. Physical activity is an important predictor of muscle mass in both sexes.

Aged↗

Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes.

OBJECTIVE: There are few data for associations of serum leptin with body fat, fat distribution, sex hormones, or fasting insulin in elderly adults. We hypothesized that the sex difference in serum leptin concentrations would disappear after adjustment for subcutaneous, but not visceral body fat. Serum leptin would not be associated with sex hormone concentrations or serum fasting insulin after adjusting for body fat and fat distribution. RESEARCH METHODS AND PROCEDURES: Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured using magnetic resonance imaging in a cross-sectional sample of 56 nondiabetic, elderly men and women aged 64 years to 94 years. Serum leptin, sex hormones (testosterone and estrone), sex hormone-binding globulin, and fasting insulin were also measured. Nine women were taking hormone replacement, and five men were clinically hypogonadal. RESULTS: Leptin was significantly associated with both SAT and VAT in each sex. Adjustment for SAT reduced the sex difference in leptin by 56%, but adjustment for VAT increased the difference by 25%. Leptin was not associated with serum estrone or hormone replacement therapy in the women, but had a significant, negative association with testosterone in the men that was independent of SAT, but not VAT. Leptin was significantly associated with fasting insulin in both sexes independent of age, sex hormones, sex hormone-binding globulin, VAT and SAT. DISCUSSION: Sex difference in serum leptin is partly explained by different amounts of SAT. Studies including both men and women should adjust for SAT rather than total body fat that includes VAT. The sex difference in serum leptin is not due to estrogen, but may be partly explained by testosterone. Testosterone is negatively associated with leptin in men, but the association is confounded with VAT. Leptin is associated with fasting insulin in nondiabetic elderly men and women independent of body fat, fat distribution, or sex hormones.

Adipose Tissue↗

Age-related changes in sex hormones affect the sex difference in serum leptin independently of changes in body fat.

Serum leptin concentrations are highly correlated with body fatness, but there is considerable variability among individuals after adjusting for differences in body fatness. Theoretically, sex hormone levels may influence serum leptin, since the levels are higher in women than in men independently of body fat. Increasing old age is associated with decreases in serum sex hormone concentrations and changes in body fatness that may independently alter serum leptin concentrations. In a cross-sectional sample of 106 men and 166 women aged 62 to 98 years, serum leptin adjusted for total body fat had a significant positive association with age in men and a nonsignificant negative association with age in women. Serum testosterone had a significant negative association with serum leptin in men after adjusting for total body fat, the fasting insulin resistance index (FIRI), and sex hormone-binding globulin (SHBG). In a longitudinal sample of 22 elderly men and 52 women, serum leptin levels increased significantly over a 14-year period in men, but not in women. Increases in serum leptin were significantly associated with decreases in serum testosterone but not with changes in the body mass index (BMI) in men. In contrast, changes in leptin were associated with changes in the BMI but not with changes in serum estrone in women. These results suggest that differences among men and changes with age in serum leptin are associated with circulating levels of testosterone. Elderly men become progressively "hyperleptinemic" with age regardless of changes in body fatness, possibly due to decreasing testosterone levels.

Adipose Tissue↗

Clinical outcomes of newborn screening for cystic fibrosis.

AIM: To determine how early diagnosis of cystic fibrosis, using neonatal screening, affects long term clinical outcome. METHODS: Fifty seven children with cystic fibrosis born before neonatal screening was introduced (1978 to mid 1981) and a further 60 children born during the first three years of the programme (mid 1981 to 1984), were followed up to the age of 10. The cohorts were compared on measures of clinical outcome, including height, weight, lung function tests, chest x-ray picture and Shwachman score. RESULTS: Age and sex adjusted standard deviation scores (SDS) for height and weight were consistently higher in children screened for cystic fibrosis than in those born before screening. At 10 years of age, average differences in SDS between groups were 0.4 (95% CI -0.1, 0.8) for weight and 0.3 (95% CI -0.1, 0.7) for height. This translates to an average difference of about 2.7 cm in height and 1.7 kg in weight. Mean FEV1 and FVC (as percentage predicted) were significantly higher in the screened cohort at 5 and 10 years of age, with an average difference of 9.4% FEV1 (95% CI 0.8, 17.9) and 8.4% FVC (95% CI 1.8, 15.0) at 10 years. Chest x-ray scores were not different between the groups at any age, but by 10 years screened patients scored an average 5.3 (95% CI 1.2, 9.4) points higher on the Shwachman score. CONCLUSION: Although not a randomised trial, this long term observational study indicates that early treatment made possible by neonatal screening may be important in determining subsequent clinical outcomes for children with cystic fibrosis. For countries contemplating the introduction of neonatal screening for cystic fibrosis, its introduction to some areas in a cluster randomised design will permit validation of studies performed to date.

Anti-Bacterial Agents↗

Effects of estradiol on substrate turnover during exercise in amenorrheic females.

The purpose of this investigation was to determine the effects of transdermal estradiol (E2) replacement on substrate utilization during exercise. Amenorrheic females (N = 6) performed three exercise trials following 72 h of placebo (C 72) and 72 and 144 h of medicated transdermal estradiol (E2) treatment (E2 72 and E2 144). Exercise involved 90 min of treadmill running at 65% VO2max followed by timed exercise to exhaustion at 85% VO2max. Resting blood samples were obtained for glucose, insulin, free fatty acids (FFA), and E2. Exercise blood samples were obtained for E2, lactate, epinephrine, and norepinephrine. Rates of appearance and disposal were calculated for glucose and glycerol using a primed, continuous infusion of [6,6-2H] glucose and [2H5] glycerol. Medicated transdermal placement increased E2 significantly at rest, before exercise (35.03 +/- 12.3, 69.5 +/- 20.1, and 73.1 +/- 31.6 pg.mL-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). Resting FFA increased significantly following E2 treatment (0.28 +/- 0.16, 0.41 +/- 0.27, and 0.40 +/- 0.21 mmol.L-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). Glucose Ra was significantly decreased during exercise as a result of E2 replacement (21.9 +/- 7.7, 18.9 +/- 6.2, and 18.9 +/- 5.6 mumol.kg-1.min-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). Average glucose Rd also decreased during exercise as a result of E2 replacement (21.3 +/- 7.8, 18.5 +/- 6.4, and 18.6 +/- 5.8 mumol.kg-1.min-1 for the C 72, E2 72, and E2 144 trials, respectively, P < 0.05). However, the estimated relative contribution of plasma glucose and muscle glycogen to total carbohydrate oxidation was similar among the trials. Epinephrine values were significantly lower late in exercise during the E2 72 and E2 144 trials, compared with the C 72 trial (P < 0.05). These results indicate that elevated E2 levels can alter glucose metabolism at rest and during moderate intensity exercise as a result of decreased gluconeogenesis, epinephrine secretion, and/or glucose transport.

Administration, Cutaneous↗

Prolonged efficacy of short acting insulin Lispro in combination with human ultralente in insulin-dependent diabetes mellitus.

Insulin Lispro is a newly FDA approved analog of human insulin that exhibits rapid absorption and a short duration of action after sc injection. Although Lispro insulin improves immediate postprandial glycemia compared to Regular insulin, long term trials of Lispro insulin have not shown improvement in overall glycemic control, as determined by glycosylated hemoglobin. We hypothesize that this lack of improvement is attributable to the development of late postprandial hyperglycemia secondary to a waning of Lispro insulin's effect in conjunction with continued meal absorption. This study was designed to evaluate the duration of Lispro-induced reductions in plasma glucose after a standardized meal when Lispro insulin is incorporated into a regimen typically employed in insulin-dependent diabetes mellitus. After establishment of euglycemia overnight, 12 healthy IDDM patients received human Ultralente insulin (0.2 U/kg) alone and in combination with each of the following treatments in random sequence immediately before ingesting a 750-Cal American Diabetes Association breakfast: 1) 0.15 U/kg human Regular insulin (Regular 0.15 group), 2) 0.15 U/kg Lispro insulin (Lispro 0.15 group), 3) 0.1 U/kg Lispro insulin (Lispro 0.1 group), and 4) an equimolar (1:1) mixture of Lispro and Regular insulins (0.15 U/kg; 1:1 Mix group). Glucose and hormonal parameters were assessed for 8 h after the meal. Peak postprandial glucose was increased in the Regular insulin group compared to that in all groups that incorporated Lispro insulin (P < 0.001). Glucose area under the curve (AUC) was decreased in the Lispro 0.15 group compared to that in the Lispro 0.1 group, and glucose AUC was decreased in the Lispro 0.15 and 1:1 Mix groups compared to that in the group given Regular insulin (P < 0.001). Mean plasma glucose concentrations during the final hour of study were increased in the Ultralente group compared with those in all other treatment groups and were increased in the Lispro 0.1 group compared with those in the Regular, Lispro 0.15, and 1:1 Mix groups (P < 0.05). Insulin AUC was significantly reduced in the Lispro 0.1 group compared to those in all other short acting insulin groups (P < 0.001), and time to peak insulin was more rapid in the two Lispro groups than those in all other treatment groups (P < 0.01). The glucagon response was significantly greater in the Ultralente group compared to those with all other treatments. There was no difference in the development of hypoglycemia between the groups. This study demonstrates that the reductions in plasma glucose effected by Lispro insulin are consistent and stable for 8 h after meal ingestion when Lispro insulin is used in combination with human Ultralente insulin. These findings suggest that improvement in overall glycemia, as assessed by glycosylated hemoglobin, may be achievable with Lispro insulin if adequate doses are administered.

Adult↗

Body protein in prepubertal children with phenylketonuria.

OBJECTIVE: To assess body protein and protein deposition in prepubertal children with phenylketonuria (PKU). DESIGN: Cross-sectional study with nested longitudinal cohort. SETTING: A tertiary referral paediatric hospital. SUBJECTS: 37 PKU patients (3.9-11.0 years) and 27 unselected healthy controls (4.0-11.5 years) of whom 29 PKU patients and 17 controls were followed longitudinally. INTERVENTIONS: All had measurements of height, weight, body fat and total body nitrogen (TBN) by neutron capture analysis; PKU patients and their unaffected siblings (n = 16) also had measurements of four day weighed food record and plasma amino acids by HPLC. RESULTS: The children with PKU compared with the controls were significantly shorter (height SD score -0.42 +/- 0.89 vs 0.17 +/- 0.94, respectively, P < 0.02) and had a lower TBN (575 +/- 200 vs 710 +/- 215g, respectively, P < 0.02). TBN in the controls was significantly correlated with lean body mass (LBM), weight, height and age (r = 0.97, 0.95, 0.95, 0.88, respectively, P < 0.001). The children with PKU had significantly lower TBN when predicted from LBM, weight and age (93%, 92%, 92% of predicted, respectively), but normal TBN predicted from height (102% of expected). The annual accretion of nitrogen was similar for the PKU and controls (86 +/- 45 and 77 +/- 58 g/y, respectively). There was no difference between the two groups in protein intake or plasma amino acids except for phenylalanine. CONCLUSION: The children with PKU had a deficit in height and body protein despite a normal to higher accretion of protein. If the deficit occurs early in life, amino acid supplementation and other nutritional practices used at this time need to be reviewed.

Amino Acids↗

Resting energy expenditure in children with phenylketonuria.

Reports have suggested that children with phenylketonuria (PKU) weigh more compared with reference data. We found lower body protein and bone mineral density in children with PKU. These children may have a predisposition becoming overweight because of an alteration in body composition, which may lower resting energy expenditure (REE). REE was measured in 30 (15 males, 15 females) children with PKU (aged 9.6 +/- 2.9 y) and in 65 (23 males, 42 females) control children (aged 11.2 +/- 3.1 y). There was a comparable range in body fat within each group (control group: 11-34%; PKU group: 10-34%). The mean REE was similar between the male and female children with PKU (5300 +/- 757 and 4703 +/- 1024 kJ/24 h, respectively) and the control subjects (5306 +/- 969 and 5164 +/- 701 kJ/24 h, respectively). The children with PKU had an REE similar to that predicted from control data (males 102.1 +/- 7.8% of predicted and females 100.2 +/- 8.5% of predicted). This study found no evidence of a reduced REE or of increased weight in children with PKU.

Adolescent↗

Hepatobiliary disease in cystic fibrosis patients with pancreatic sufficiency.

Focal and multilobular biliary cirrhosis are considered pathognomonic of cystic fibrosis (CF) and almost invariably have been reported in patients with steatorrhea. In contrast, patients with pancreatic sufficiency and normal absorption are considered less likely to develop liver or biliary tract problems. The authors report three patients with CF and pancreatic sufficiency, presenting with recurrent abdominal pain (unrelated to pancreatitis). All had common bile duct disease, one with multilobular cirrhosis and portal hypertension. Pancreatic sufficiency was proven by quantitative pancreatic stimulation tests, 3-day fecal fat analyses, and serum pancreatic isoamylases. All three patients had mild lung disease. Two were homozygous for the common delta F508 mutation, and the other, a delta F508 compound heterozygote. Hepatobiliary structure and function were determined by serial hepatobiliary scintigraphy, percutaneous transhepatic cholecystography, and biochemical liver function tests. Patients 1 and 3 had mild hepatomegaly, normal liver biochemistry, and distal common bile duct strictures. Patient 2 had a firm nodular liver with splenomegaly, abnormal liver biochemistry, and a cholangiographic appearance of sclerosing cholangitis. All have undergone operative treatment for persistent abdominal pain. These cases confirm the occurrence of common bile duct pathology and liver disease in patients with CF and pancreatic sufficiency. They demonstrate that liver and biliary tract disease can occur independently of the underlying disease severity and the presence of steatorrhea. Further, they suggest that obstruction of the biliary tract may be an additional factor in the evolution of liver disease in CF.

Biliary Tract Diseases↗

Decreased bone mineral density in children with phenylketonuria.

Previous studies have suggested that children with phenylketonuria (PKU) have a reduction in bone mineralization compared with control subjects. To investigate this, bone mineral density (BMD) of the total body (TBMD) was measured in 32 prepubertal children with PKU and in 95 age-matched control subjects. Spine bone mineral density (SBMD) was also recorded in a subset, 24 with PKU and 55 control subjects. The effect of dietary intake on bone mass was assessed in 30 of the children with PKU and in 12 control subjects. In the children with PKU, TBMD and SBMD were significantly lower than in the control subjects after adjustment for height and weight (P = 0.03 and P = 0.003, respectively). The children with PKU had a higher intake of calcium (P < 0.0001), phosphorus (P = -0.0002), and magnesium (P < 0.0001), suggesting that their lower BMD occurred despite an adequate diet based on current recommendations. Further study is needed to establish the cause of this deficit in bone mass and the benefit of additional nutritional support to reverse this problem.

Absorptiometry, Photon↗

Nitrogen deposition in malnourished children with cystic fibrosis.

To determine the protein nutritional status of 21 malnourished children with cystic fibrosis (CF), total body nitrogen (TBN) was measured and the results were compared with 21 control subjects. CF patients demonstrated a lower TBN (P less than 0.001). When matched for height (n = 10) or bone age (n = 13), the CF patients still had a depressed TBN/height or TBN/lean body mass (P less than 0.05). To assess nitrogen deposition during nutritional rehabilitation, repeat TBN measurements were performed on the 21 CF patients. Nitrogen deposition ranged from -230 to 550 g/y and correlated with weight velocity (r = 0.78, P less than 0.001). Increased nitrogen deposition (greater than 150 g/y) was generally associated with normal height gain (height velocity SD score greater than -2.00) and weight gain (greater than 2.0 kg/y). Decreased nitrogen deposition was associated with poor weight gain but did not preclude normal linear growth. These data suggest an important role for TBN estimations in defining protein nutritional status in children and indicate that skeletal growth can continue in the presence of minimal nitrogen deposition.

Adolescent↗

Pancreatic function in infants identified as having cystic fibrosis in a neonatal screening program.

The use of the dried-blood immunoreactive-trypsin assay for the detection of cystic fibrosis in newborns has been questioned on the grounds that it may fail to identify patients with enough pancreatic function to have normal fat absorption. To investigate this possibility, we assessed pancreatic function in 78 patients identified in a neonatal screening program as having cystic fibrosis. The diagnosis of cystic fibrosis was confirmed by abnormal results on a sweat chloride test. The results of measurements of fecal fat excretion, pancreatic-stimulation tests, and estimations of the serum level of pancreatic isoamylase indicated that 29 of the 78 children (37 percent) had substantial preservation of pancreatic function. These children (median age, four years) had growth that was close to normal and comparable to growth in children with severe pancreatic insufficiency who received oral enzyme therapy. Pancreatic insufficiency subsequently developed in 6 of the 29 patients, at 3 to 36 months of age. We conclude that the serum immunoreactive-trypsin assay used in neonatal screening programs identifies patients with cystic fibrosis who have sufficient pancreatic function to have normal fat absorption and that a substantial proportion of infants identified as having cystic fibrosis are in this category.

Child, Preschool↗