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Failure to thrive.

Reviewing the chronological evolution of our understanding of why some children fail to thrive without obvious organic cause permits us to develop a rational contemporary approach to diagnosis and management. Originally recognized as a phenomenon of children living in institutions, it later became clear that it could occur in children living with their families. While emotional deprivation was at first emphasized as the principal determinant of growth failure, it is now apparent that the major mediating mechanism is insufficient caloric intake. Thus prior to nutritional recovery it may be difficult to segregate whether emotional symptoms in the child reflect the causes or effects of malnutrition. With rare exceptions, an etiologic diagnosis can be suspected on the basis of history, physical examination, and family assessment. Nonspecific investigative screening of such children has proved to be without value. Successful management depends on recognition of the supernormal caloric intake required to induce rapid catch-up growth. Aggressive hyperalimentation combined with intensive emotional stimulation and often with active family participation offer the best chances of a successful outcome.

Aftercare↗

Depressive symptoms and the risk of type 2 diabetes: the Atherosclerosis Risk in Communities study.

OBJECTIVE: The goal of this study was to determine whether depressive symptoms predict type 2 diabetes. RESEARCH DESIGN AND METHODS: We analyzed data on depressive symptoms (including recent fatigue, sleep disturbance, feelings of hopelessness, loss of libido, and increased irritability) in a longitudinal, biracial cohort study of 11,615 initially nondiabetic adults aged 48-67 years, who were subsequently followed for 6 years for the development of type 2 diabetes. RESULTS: At baseline, depressive symptoms were positively associated with BMI, fasting insulin, systolic blood pressure, caloric intake, physical inactivity, and current smoking (all P < 0.05). In prospective analyses, after adjusting for age, race, sex, and education, individuals in the highest quartile of depressive symptoms had a 63% increased risk of developing diabetes compared with those in the lowest quartile (relative hazard [RH] 1.63, 95% CI 1.31-2.02). This relation persisted after adjustment for stress-associated lifestyle factors (smoking, physical activity, caloric intake, and adiposity) (1.28, 1.02-1.60) and metabolic covariates (fasting insulin and glucose, lipids, blood pressure, and adiposity) (1.38, 1.10-1.73). CONCLUSIONS: In this cohort, depressive symptoms predicted incident type 2 diabetes. This relation is only partially explained by demographic, metabolic, and lifestyle factors. Possible neuroendocrine mediators of the stress-obesity-diabetes relationship require further evaluation in prospective cohort studies that use an established tool to assess depression and incorporate neurohormonal measurements.

Arteriosclerosis↗

Dehydroepiandrosterone and macronutrient selection by obese Zucker rats (fa/fa).

The effect of dehydroepiandrosterone (DHEA) on the macronutrient preference and total energy intake of lean and obese female Zucker rats was studied. Introduction of DHEA led to a rapid decrease in the consumption of fat, protein and total calories by the obese rat. DHEA treatment of the lean rat caused a change neither in its total energy consumption nor in its fat consumption, but did cause a distinct expression of preference for carbohydrate over protein. Both lean and obese animals gained weight rapidly during the steroid-free weeks and lost weight while consuming the DHEA-supplemented diet. The difference in weight changes seen with the obese rats between the DHEA-free and DHEA-supplemented periods could be accounted for by differences in caloric intake. Lean rats, however, did not change their total energy intake during DHEA-treatment periods; therefore, DHEA caused weight loss in the lean rat probably by altering energy metabolism. It is concluded that in the obese, young, female Zucker rat, DHEA alters macronutrient preference as well as caloric intake. In the lean rat, DHEA has a more subtle effect on relative macronutrient preference and not on total energy consumption.

Animals↗

Identification of intranasal oxytocin plasma proteome signatures.

BACKGROUND: The hypothalamic peptide oxytocin regulates a range of central and peripheral activities, ranging from uterine contractions to energy homeostasis. Oxytocin-based therapeutics are under investigation for neuropsychiatric and metabolic disease, including obesity. The mechanisms underlying oxytocin effects are poorly understood. This study profiles 4725 serum proteins in 19 healthy men across the adiposity spectrum (9 normal-weight, BMI&#x2009;<&#x2009;25&#x2009;kg/m2; 10 overweight/obese, BMI &#x2265; kg/m2) following exogenous, intranasal oxytocin administration to identify markers of pharmacodynamic effect. METHODS: In a double-blind, randomized controlled crossover design, 25 men were exposed to a single dose of 24 IU intranasal oxytocin vs. placebo. Fasting blood was drawn immediately prior and at 15, 30, and 55 min after oxytocin/placebo administration for proteomic analysis (SOMA Scan, Soma Logic, Inc.). RESULTS: As previously reported in the parent study, intranasal oxytocin reduced caloric intake at the test meal; here, we examined proteomic predictors of this behavioral effect. Proteomic data was available for 19 men. We identified 198 differentially expressed proteins in response to intranasal oxytocin in fasting men across the adiposity spectrum. The pathways identified are involved in intracellular signaling pathways, as well as immune regulation and inflammation. Oxytocin modulated a cluster of proteins that was associated with subsequent caloric intake at the test meal. CONCLUSIONS: These data provide insights into mechanisms underlying pharmacologic oxytocin effects on human physiology and a framework for future investigations.

Humans↗

Percutaneous endoscopic gastrostomy in children--a 5-year experience.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) has been performed on children since 1979. The indications for a PEG are wide ranging and while there are well-established benefits, it remains a procedure with recognised complications. GOALS AND OBJECTIVES: The goal of this study was to review our experience with this procedure at a South African paediatric tertiary referral hospital over a 5-year period. The objectives were to review PEGs with regard to patient characteristics, indications, anaesthesia time required and complications. METHODS: The study was a retrospective case record review. RESULTS: A total of 70 PEGs were performed. Patients had a mean age of 4 years and 3 months, and a mean weight of 12.2 kg at the time of performing the procedure. The mean anaesthetic time required for performing a PEG was 27 minutes. Fifty-four PEGs (77%) were performed for inability to swallow, 15 (21%) to improve caloric intake, and 1 (1%) for continuous enteral feeding. There were no deaths, 5 patients had major complications (6%), and 12 patients (17%) needed antireflux surgery subsequent to the placement of a PEG. DISCUSSION: There is an increasing demand for PEGs at our institution. The indications for a PEG in this series are similar to those reported in other series, although we may be underutilising PEGs to improve caloric intake. Our complication rates compare favourably with those reported in other series. We have, however, identified post-PEG gastrooesophageal reflux disease as a complication we would like to reduce, and suggest a practical approach to do so.

Adolescent↗

Effect of dietary carbohydrates during hypocaloric treatment of obesity on peripheral thyroid hormone metabolism.

The effect of different hypocaloric carbohydrate (CHO) intakes was evaluated in 8 groups of obese patients in order to assess the role of the CHO and the other dietary sources in modulating the peripheral thyroid hormone metabolism. These changes were independent of those of bw. Serum T3 concentrations appear to be more easily affected than those of reverse T3 by dietary manipulation and CHO content of the diet. A fall in T3 levels during the entire period of study with respect to the basal levels occurred only when the CHO of the diet was 120 g/day or less, independent of caloric intake (360, 645 or 1200 calories). Moreover, reverse T3 concentrations were found increased during the entire period of study when total CHO were very low (40 to 50 g/day) while they demonstrated only a transient increase when CHO were at least 105 g/day (with 645 or more total calories). Indeed, our data indicate that a threshold may exist in dietary CHO, independent of caloric intake, below which modifications occur in thyroid hormone concentrations. From these results it appears that the CHO content of the diet is more important than non-CHO sources in modulating peripheral thyroid hormone metabolism and that the influence of total calories is perhaps as pronounced as that of CHO when a "permissive" amount of CHO is ingested.

Adult↗

Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity-related hypertension (or, how insulin affects blood pressure, and why).

Thus, the evidence summarized here supports an important role for insulin and the sympathetic nervous system in the pathogenesis of obesity-related hypertension. Is it possible that insulin-mediated sympathetic stimulation contributes a pro-hypertensive effect in non-obese as well? It seems possible in young borderline hypertensives where sympathetically mediated thermogenic mechanisms are potent enough to compensate for the increased caloric intake, thereby enabling these young hypertensives to avoid obesity. This is consistent with an observation made in the original Framingham cohort that not only did obesity predict the eventual development of hypertension, but hypertension, as well, predicted the eventual development of obesity. A reasonable interpretation of these data suggests that as subjects age and the effectiveness of thermogenic mechanisms wanes, obesity might develop as a consequence of increased caloric intake no longer effectively buffered by the increased SNS activity. It is important to note that the mechanisms described here exert a pro-hypertensive effect and cannot properly be considered to 'cause' hypertension. Hypertension is rarely the consequence of a single mechanism. It is also true, as pointed out convincingly by Julius and his colleagues, that enhanced sympathetic activity, as a primary factor, can be associated with both hypertension, insulin resistance and, possibly, obesity [39]. And, finally, it should be noted that the mechanism described here is not the only mechanism linking obesity and hypertension. A rapidly emerging body of evidence indicates that leptin, the polypeptide product of the ob/ob gene secreted from adipose tissue, exerts potent central neural effects on both appetite and sympathetic activity. Leptin levels, elevated in obese humans, have the potential to increase both sympathetic activity and blood pressure [40-43]. A more comprehensive summary of the relationships between hypertension and obesity may, therefore, involve insulin and leptin, as well as the SNS, as represented in the schema presented in Figure 7. Both leptin and insulin may, therefore, be considered as compensatory mechanisms recruited to restore energy balance, with the SNS as one of the effector arms. Viewed in this way, obesity-related hypertension is inextricably linked to the metabolic economy of the obese.

Animals↗

Disuse atrophy alterations in normal and low temperature environments during hindlimb unloading in Syrian hamsters.

This study examined whether a hypothermic environment reduces experimentally-induced atrophy of skeletal muscle, as judged by histochemical findings. The hind limbs of hamsters in a hypothermic group were suspended and flexed into plantar positions at the ankle joint, and housed for one week at 8 to 12 degree celsius in a temperature-controlled room, while the normothermic group was housed at 23 to 25 degree celsius. Hypothermia did not significantly alter the average caloric intake, and the animals from the hypothermic group lost a significant amount of body weight when compared with the normothermic group. The hypothermic group retained more muscle wet-weight and myofibers cross-sectional area in the soleus and gastrocnemius muscles compared with the normothermic group. Our results indicate that a hypothermic environment inhibits short-term muscle atrophy. This inhibition may be caused by the increased caloric intake combined with a state similar to hibernation in low-temperature environments.

Animals↗

Improved growth of three uremic children by nocturnal nasogastric feedings.

Three children with high-output renal insufficiency (estimated creatinine clearance, 20 to 25 mL/min/1.73 sq m) and linear and ponderal growth retardation were administered nocturnal nasogastric (NG) feedings at home by trained parents. The NG feedings were initiated at 50 kcal/kg/night and increased as needed to establish and maintain weight gain. Nocturnal feedings were continued for 13.5, 16, and 11 months, respectively. Improved caloric intake reestablished the velocity of weight gain from less than 5% to greater than 95% in each patient. Linear growth velocity improved from less than 5% in two patients and 40% in one patient to greater than 95% in two patients and 80% in the third patient. No change was observed in serum creatinine, electrolyte, calcium, or phosphorus levels. The serum urea nitrogen level remained below 100 mg/dl. Ensuring adequate caloric intake by nocturnal NG feedings, in addition to standard therapy, improved both ponderal and linear growth velocity.

Enteral Nutrition↗

Energy expenditure, energy intake and prevalence of obesity after therapy for acute lymphoblastic leukemia during childhood.

OBJECTIVES: To investigate the prevalence and potential risk factors of obesity after therapy for childhood acute lymphoblastic leukemia (ALL). STUDY DESIGN: 39 ALL patients (age 10.7-20.5 years) who were in first remission for 3.4-14.6 years after standardized treatment with chemotherapy plus cranial irradiation (n = 25) or with chemotherapy alone (n = 14) were examined. After fasting overnight, the following parameters were investigated: body mass index (BMI) of patients and their parents; patients' BMI before ALL therapy; serum free thyroxin, growth hormone-dependent factors, estradiol, testosterone, cortisol, leptin and c-peptide; fat-free mass (bioelectrical impedance); resting metabolic rate (RMR, indirect calorimetry); caloric intake (24-hour recall); and physical activity (questionnaire). RMR data were applied to the fat-free mass and compared with 83 controls. RESULTS: The prevalence of obesity (criterion: BMI > 2 SDS) was significantly (p < 0.05) higher after ALL therapy (38%; irradiated patients 48%, non-irradiated patients 21%) than before therapy (3%). Compared to non-irradiated patients, irradiated patients had significantly lower RMRs (-1.07 +/- 0.24 vs. -0.32 +/- 0.21 SDS; p < 0.05), reduced physical activity levels (1.41 +/- 0.03 vs. 1.52 +/- 0.03; p < 0.05), and lower concentrations of insulin-like growth factor-binding protein-3 (-0.65 +/- 0.17 vs. 0.25 +/- 0.33 SDS; p < 0.05) and of free thyroxin (1.17 +/- 0.06 vs. 1.38 +/- 0.08 ng/dl; p < 0.05). Caloric intake was adequate. CONCLUSIONS: After ALL during childhood, patients face a higher risk of obesity. In the cranially irradiated patients, the likely causes are low physical activity, RMRs and hormonal insufficiency.

Adolescent↗

Effect of sucrose overfeeding on Na,K-ATPase-mediated 86Rb uptake in normal and ob/ob mice.

When normal mice have their usual chow diets supplemented by free access to a solution of 10% sucrose, their caloric intake increases by about 30%. We have used this model to explore the effects of sucrose overfeeding on Na,K-ATPase-mediated cation transport. After 5 days of sucrose supplementation, Na,K-ATPase mediated K uptake is increased by 88% in liver slices and 26% in intact soleus muscles of these animals. Ob/ob mice are hyperphagic on an ad libitum chow diet, and they display even greater increments in caloric intake than do thin controls when similarly allowed access to sucrose. Despite hyperphagia while on a chow diet, Na,K-ATPase-mediated K uptake by liver slices of ob/ob mice is not significantly different from that of their thin littermates. In addition, Na,K-ATPase-mediated K uptake into liver slices of ob/ob mice does not significantly increase while on sucrose supplements. These findings demonstrate the influence of dietary factors on Na,K-ATPase-mediated ion transport in liver and muscle of normal mice, and suggest that ob/ob mice may have an impairment in such dietary control. These observations suggest an important role for nutritional factors in the overall regulation of monovalent cation transport, and may also have relevance for our understanding of the cellular mechanisms of dietary thermogenesis.

Animals↗

Dietary ethanol does not accelerate bone loss in ovariectomized rats.

The abuse of alcohol is a behavior that can significantly compromise skeletal health. Because postmenopausal women are already at risk for low bone mass and osteoporotic fracture, this investigation sought to determine whether high concentrations of dietary ethanol exacerbate the bone loss associated with ovariectomy in rats, an animal model of human postmenopause. Six-month-old Sprague-Dawley rats were ovariectomized or sham-operated and randomly divided into groups fed a modified Lieber-DeCarli liquid diet isocalorically supplemented with 0%, 13%, or 35% ethanol (by daily caloric intake), for a period of 2 months. All animals were injected with fluorochromes at the start, 2 weeks, and 2 days before sacrifice to label mineralizing bone surfaces. At sacrifice, blood, uterus, and tibiae were harvested. No differences in serum calcium or cholesterol were found. Serum creatinine was also found to be unvaried, indicating this level of alcohol consumption did not compromise liver function. Dietary alcohol consumption at 35% of daily caloric intake was determined to increase tibial cortical medullary area and endocortical perimeter, while not affecting cortical area and periosteal perimeter. Ovariectomy significantly increased indices of bone turnover and resulted in cancellous bone loss, whereas alcohol consumption had no additional detrimental effects. This was a consistent pattern for other indices of proximal tibial architecture. In summary, this investigation has found that chronic ingestion of high concentrations of alcohol does not accentuate bone loss in ovarian hormone-deficient adult female rats.

Adult↗

Differential effects of amphetamine and fenfluramine on dietary self-selection in rats.

Daily caloric intakes and dietary self-selection of the three macronutrients, protein, fat and carbohydrate were examined in female rats following administration of d-amphetamine sulfate (0.0, 0.5, 1.0 and 2.0 mg/kg, IP) or fenfluramine hydrochloride (0.0, 1.5, 3.0 and 6.0 mg/kg, IP). Animals were maintained on ground Purina Chow or one of two self-selection regimes, one with a high-caloric fat ration (7.85 kcal/g) and the other with a fat ration isocaloric to the carbohydrate and protein rations (3.76 kcal/g). Animals received drug injections at the beginning of a daily 8-hour feeding period with nutrient intakes measured at 2, 4 and 8 hrs following injections. While both amphetamine and fenfluramine lef to dose-related decreases in total caloric intakes, the two drugs resulted in different temporal patterns of feeding. Amphetamine produced its greatest effect on caloric intake during the first 2 hours of the feeding period, whereas fenfluramine suppressed caloric intake equivalently across the 8-hour feeding period. The two anorectic drugs also led to different patterns of nutrient choice. When animals were given the high-caloric fat ration, amphetamine selectively decreased fat intake while fenfluramine produced decreases in both protein and fat intakes, sparing carbohydrate intake. In contrast, when animals were given the isocaloric fat ration, amphetamine resulted in a general suppression of nutrient intakes while fenfluramine led to a sustained decrease in fat intake with a relative sparing of protein and carbohydrate consumption.

Amphetamine↗

Correction of anemia in patients with congestive heart failure increases resting energy expenditure.

BACKGROUND & AIM: Congestive heart failure (CHF) and anemia were reported to affect resting energy expenditure (REE). The aim of this study was to evaluate the effect of the correction of anemia on REE in subjects with CHF. PATIENTS AND METHODS: Nine anemic patients with compensated CHF and CRF were studied before and after correction of anemia. REE was studied by an open circuit indirect calorimeter, body composition by dual-energy-X-ray absorption and total body and extracellular water by multi-frequency bioelectrical impedence. Four anemic and 5 non-anemic CHF patients who did not receive any new treatment served as controls. RESULTS: After the correction of their anemia patients tended to increase weight (P<0.06), but no significant changes were observed in body composition. Daily caloric intake increased significantly (P<0.02). Ejection fraction increased (P<0.05) and pulse rate decreased significantly (P<0.001). REE and REEPP were in the normal range before correction but increased significantly afterwards (1402+/-256 vs. 1496+/-206 kcal/d, and 101+/-9 vs. 109+/-8, P<0.023 and P<0.006, respectively). CONCLUSION: Correction of anemia in patients with CHF increases their REE. This can be related either to improved tissue oxygenation and/or to increased caloric intake.

Aged↗

Physiological aspects and clinical sequelae of energy deficiency and hypoestrogenism in exercising women.

Amenorrhoea associated with reduced caloric intake and strenuous exercise leads to hypoestrogenism and is associated with clinical manifestations that include disordered eating, stress fractures, osteoporosis, and, as recently reported, a potential increase in the risk of premature cardiovascular disease. Disordered eating, menstrual irregularities and bone loss comprise the clinical condition known as the 'female athlete triad'. The aetiology of the triad is linked to a high prevalence of disordered eating and cognitive restraint. This results in inadequate caloric intake for high exercise energy expenditures that leads to energy deficiency. This in turn stimulates compensatory mechanisms, such as weight loss or energy conservation, subsequently causing a central suppression of reproductive function and concomitant hypoestrogenism. Because the aetiology of menstrual disturbances and the female athlete triad is causally linked to energy deficiency, there is no justification for fears that exercise itself is unhealthy for women. However, improved detection, monitoring, and treatment of all components of the triad in exercising women should be emphasized. This paper critically reviews the physiological aspects and clinical sequelae of energy deficiency and hypoestrogenism associated with the female athlete triad in exercising women.

Amenorrhea↗

Dietary-induced severe obesity: a rat model.

In this study, dietary intervention before and after weaning was used to produce body fatness in adult rats ranging from severe obesity (61% body fat) to the lean condition (18% body fat). To produce severe obesity, rats were programmed for a high caloric intake during suckling. After weaning, they were provided unrestricted access to a diet in which approximately 40% of the calories were derived from fat (high-fat diet). The high-fat diet appeared to cause hyperphagia such that appetites were highly stimulated between 29 and 58 wk of age. Body weight in these rats stabilized at 1,213 +/- 62 g. Severe obesity was also observed in rats programmed for a low caloric intake if, after weaning, they ate the high-fat diet (59% body fat). These results provide evidence that the fat content of the diet may play a regulatory role in the development of severe obesity.

Adipose Tissue↗

Effects of diet and body fat content on cold-induced anestrus in Syrian hamsters.

Mammalian reproduction is inhibited by food shortages, increased foraging requirements, and other factors that decrease the energy available for biological processes. Cold-induced inhibition of reproduction may result from a depletion of available metabolic energy due to the increased requirements for thermogenesis or, alternatively, from mechanisms unrelated to energy expenditure. We examined the relationship between energy availability (in the diet and the body fat stores) and cold-induced anestrus in Syrian hamsters. In experiment 1, hamsters were housed in the cold (5 degrees C) and fed diets that differed in the amount of effort required to ingest them. The number of consecutive estrous cycles was positively correlated with caloric intake and negatively correlated with body weight loss in the cold. In experiment 2, hamsters were fed these diets for several weeks, so that they differed dramatically in body weight and fat content before cold exposure. Half of each group retained the same diet during cold exposure, whereas the other half were fed a regular chow diet. The effects of body weight before cold exposure were less pronounced than the effects of caloric intake during cold exposure. In experiment 3, females were fed different diets before cold exposure, then, during cold exposure, all were fed in a manner that decreased food intake and increased the effort required to obtain food. This energetic challenge exaggerated the effect of prior body weight on the latency to cold-induced anestrus. Thus the latency to cold-induced anestrus in Syrian hamsters is primarily a function of the availability of metabolic energy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Ethanol inhibition of pituitary-thyroid axis: an effect secondary to nutritional deficiency.

Ethanol as either 20% or 36% of total calories in a Lieber diet was administered to male rats. At these concentrations, ethanol consumption relative to body weight did not differ. Pair-fed controls were restricted to the amount of calories consumed by rats given ethanol. Under these conditions, a direct effect of ethanol on the hypothalamic-hypophyseal-thyroid axis could not be demonstrated. There were no differences between pair-fed control and ethanol treated rats in serum or pituitary TSH, TSH response to TRH, or T4 and T3 levels. On the other hand, in rats given ethanol as 36% of total calories ("36%" ethanol-treated), and in their pair-fed controls, a marked decrease in serum T4 levels occurred (25% and 30%), relative to the corresponding "20%" groups. The decreased T4 in the "36%" groups was associated with a pronounced fall in caloric intake, decreased serum TSH, and declines in adenohypophyseal and body weights -- all of which were of similar magnitude in experimental and control rats. Thus, inanition was probably the primary cause of reduced thyroid function in the "36%" groups. An interesting aspect of this change was the finding of no difference in serum T3 levels between pair-fed control and ethanol treated rats in the 36% and 20% groups despite the reduced T4 and caloric intake in 36% animals; the lack of decrease in T3 concentration in 36% animals may reflect augmented peripheral conversion of T4 to T3 or reduced T3 clearance.

Animals↗