Clinical presentation of hypernatremic dehydration in exclusively breast-fed neonates.

OBJECTIVE: To identify the clinical presentation of dehydration related to failure of lactation in exclusively breast-fed term infants. METHOD: A prospective study was performed between January 2000 and June 2003 in Al Qassimi Hospital in the Emirate of Sharjah. Enrollment criteria included term neonates whose birth weight of > 2000 g with no underlying organic illness causing poor feeding admitted for clinical manifestations of dehydration with weight loss of > 10% during the first 2 weeks of life. The control group, a non-randomized sample included healthy full term neonates, seen in Sharjah maternal and child health care center at 4-7 days old for their routine Guthrie screening test. For each dehydrated neonate we took two neonates as controls. Mother's age, parity, length of pregnancy, any pathologic conditions, breastfeeding history and her level of knowledge of lactation was recorded. Neonatal information included mode of delivery, percentage of weight loss, clinical examination, and stool and urine output the previous day. Data was analyzed with Student 't' test and chi-square test. RESULTS: Out of 17208 live births, 29 neonates between the ages of 2-13 days were admitted with weight loss of between 12 and 29% (dehydrated group). 27 patients had hypernatremic dehydration with serum sodium level ranging from 150 to 195 mmol/l. Mean age of admission was 4.9 days. Reasons for admission were: signs of dehydration (55%); hyperthermia (55%); hypoglycemia (27%) and jaundice (59%). The control group included 58 healthy neonates. Their birth weight and age were comparable to those in the dehydrated group. In comparison with the control group, delivery by cesarean section (P< 0.0001), lower level of maternal breastfeeding knowledge (P=0.03), transient inadequate breast milk quantity (P=0.005) and nipple anomalies (P=0.001) was significantly more common in the dehydrated group. Fewer voidings of urine (< 6 times /day) and stool (< 3 times/day) in the previous 24 hours before admission was more frequently observed in the dehydrated group (P < 0.0001). CONCLUSION: Low level of maternal knowledge in lactation, cesarean section and failure of early postnatal follow up was associated with the neonatal dehydration. Decreased urine and stool frequency might be considered as a warning for failure of lactation.

Weight Loss in patients with diabetes treated with a metformin-sulfonylurea combination in comparison with twice-daily mixed insulin.

OBJECTIVE: To investigate whether patients previously treated with insulin or sulfonylureas alone can be transferred to a combination of sulfonylureas and metformin therapy and realize a prolonged weight loss. METHODS: We conducted a retrospective review of medical records to identify three groups of patients with type 2 diabetes: group 1, those requiring insulin who had remained on a daily regimen of two injections of mixed insulin; group 2, patients whose regimen had been changed from sulfonylureas alone to a combination of a sulfonylurea and metformin; and group 3, patients whose regimen had been converted from twice-daily mixed insulin alone to a sulfonylurea-metformin combination. Results relative to loss of weight in these three groups were analyzed. RESULTS: For a 12-month period, no significant weight loss was noted in group 1, and group 2 showed a small nonsignificant weight loss in 6 months. Only group 3 had a significant weight loss at 3, 6, 9, and 12 months, maximizing at a mean weight loss of 22 lb (10 kg) at 12 months. In addition, in those patients in whom data were available, a significant weight loss was found at 18 and 21 months. At 21 months, however, weight began to increase. Percentage weight loss followed a pattern similar to that seen with total weight loss. The proportion of patients losing weight did not differ significantly in groups 1 and 2; however, in group 3, after 3 and 12 months a significant proportion of patients (79% and 86%, respectively) had lost weight. Race, gender, or baseline body weight had no effect on weight loss. CONCLUSION: From this retrospective study of patients with type 2 diabetes, we conclude that conversion from insulin to combination oral therapy with sulfonylureas and metformin results in a significant weight loss for up to 21 months.

Addition of various carbohydrates to beef burgers affects the formation of heterocyclic amines during frying.

The influence of the addition of carbohydrates with different physicochemical properties on weight loss and formation of heterocyclic amines (HAs) during the frying of beef burgers was examined. Furthermore, the capability of carbohydrates to bind HAs was tested. Beef burgers containing 1.5% NaCl and 0.3% tripolyphosphate (reference), with the addition of 1.5% carbohydrate, were fried for 5 min at 200 degrees C in a double-sided pan fryer. The beef burgers were analyzed for HAs with solid phase extraction and liquid chromatography/mass spectrometry. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), and 9H-pyrido[3,4-b]indole (Norharman) were detected in all of the beef burgers. The addition of carbohydrates affected both the weight loss and the formation of HAs during cooking. The formation of HAs could be correlated to depend on both the weight loss and the type of the added carbohydrate. Of the 11 different carbohydrates tested, raw potato starch was most capable of inhibiting the formation of HAs, while potato fiber gave the lowest weight loss and a comparably low amount of PhIP. Wheat bran and potato fiber were found to reversibly bind HAs. It is concluded that adding small amounts of certain carbohydrates may be a simple and effective way of reducing the amount of HAs and can easily be applied in households and commercial preparations of beef burgers.

Skeletal muscle enzymes as predictors of 24-h energy metabolism in reduced-obese persons.

BACKGROUND: Little is known about the effects of weight loss on the relation between skeletal muscle enzymes and energy metabolism. OBJECTIVE: This study was performed retrospectively to investigate the relation between skeletal muscle enzymes and 24-h energy metabolism in obese persons before and after weight loss. DESIGN: Ten women and 9 men [with body mass indexes (in kg/m(2)) > 30] underwent a 15-wk weight-loss program (-700 kcal/d). Body weight and composition, 24-h energy metabolism (whole-body indirect calorimetry), and maximal activities of phosphofructokinase (EC 2.7.1.11), creatine kinase (CK; EC 2.7.3.2), citrate synthase (CS; EC 4.1.3.7), 3-hydroxyacyl-CoA dehydrogenase (HADH; EC 1.1.1.35), and cytochrome-c oxidase (COX; EC 1.9.3.1) were determined from biopsy samples of the vastus lateralis taken before and after weight loss. RESULTS: Before weight loss, fat-free mass (FFM) was the only predictor of 24-h energy expenditure (R(2) = 0.70, P < 0.001), whereas the cumulative variance in sleeping metabolic rate explained by FFM and fat mass (FM) was 83% (P < 0.001). After weight loss, CS (r = 0.45, P = 0.05) and COX (r = 0.65, P < 0.01) were significantly associated with 24-h energy expenditure, whereas CK (r = 0.53, P < 0.05), CS (r = 0.45, P < 0.05), COX (r = 0.64, P < 0.01), and HADH (r = 0.45, P = 0.05) were all significant correlates of sleeping metabolic rate. After weight loss, FFM, FM, and COX explained 84% (P < 0.01) of the variance in 24-h energy expenditure, whereas FFM, FM, and CK all contributed to the cumulative variance in sleeping metabolic rate explained by this model (R(2) = 0.82, P < 0.05). CONCLUSION: Maximal activities of key skeletal muscle enzymes contribute to the variability in 24-h energy metabolism in reduced-obese persons.

ASHP therapeutic position statement on the safe use of pharmacotherapy for obesity management in adults. Developed by the ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on April 23, 2001.

Obesity is a chronic disease that may require pharmacologic treatment in select patients at high risk in whom lifestyle modifications alone were unsuccessful. Although long-term therapy may be indicated in these patients, long-term safety and efficacy data for the current agents are not available. Patients should be informed of all known risks of therapy and, together with their health care providers, carefully consider the risks and benefits of treatment. Patients should be informed that pharmacotherapy has been proven to produce modest weight loss (10% weight loss) when used in conjunction with lifestyle modifications. The health benefits of modest weight loss should be stressed, and lifestyle changes should be continuously encouraged. Pharmacists can take an active role in the management of obesity by assisting in the selection of weight-loss agents and providing appropriate counseling and monitoring to ensure safe and effective drug therapy outcomes for patients using prescription and nonprescription products. Further evaluation of current and future therapies will be necessary to determine the role of long-term pharmacotherapy for the management of obesity.

Weight reduction and pharmacologic treatment in obese hypertensives.

This study was conducted to evaluate the mechanisms of weight loss-induced blood pressure (BP) reduction focusing, in particular, on the contributions of sympathetic nervous system activity, fasting plasma insulin, and leptin to BP levels, and to delineate the additional influence of antihypertensive drug therapy. Each of five groups of obese hypertensives were treated with the long-acting calcium channel blocker (CCB) amlodipine, the angiotensin converting enzyme (ACE) inhibitor enalapril with or without a weight reduction program, or a weight reduction program alone. The goal BP was less than 140/90 mm Hg for the pharmacologic treatment groups. The weight reduction program groups with or without pharmacologic treatment were divided into two groups; weight loss groups who succeeded in weight reduction (> or = 10%) and nonweight loss groups who failed in weight reduction (<10%) in the first 6 months. The final dose of CCB and ACE inhibitor were less in the combined pharmacologic and weight loss groups than in the pharmacologic treatment alone groups or in the pharmacologic and nonweight loss groups. In the weight reduction groups regardless of pharmacologic treatment, the percent reductions from baseline in plasma insulin, leptin, and norepinephrine (NE) were greater in the weight loss groups (> or = 10%) than in the nonweight loss groups (<10%). The reductions in plasma NE, insulin, and leptin were significantly greater and earlier in combined pharmacologic and weight loss groups than in the pharmacologic treatment alone groups. In ACE inhibitor groups, the reductions in plasma NE, in insulin, and especially in leptin were greater than the other groups. In the CCB alone group, reductions in insulin and leptin occurred, but there was no change in plasma NE. Reductions in insulin and leptin in CCB groups were less and occurred later than in the ACE inhibitor groups or the weight reduction alone group. These results show that weight loss associated with favorable metabolic improvements and these improvements are amplified when combined with pharmacologic treatment. Therefore, weight loss should be regarded as an essential component of any treatment program for obesity-related hypertension. A novel finding from this study is that ACE inhibition had a striking effect to lower plasma leptin. Suppression of sympathetic activity, insulinemia, and leptinemia appeared to play a role in the BP reduction accompanying weight loss.

Weight Loss in rats exposed to repeated acute restraint stress is independent of energy or leptin status.

Acute release of corticotropin-releasing factor (CRF) during repeated restraint (3-h restraint on each of 3 days) causes temporary hypophagia but chronic suppression of body weight in rats. Here we demonstrated that a second bout of repeated restraint caused additional weight loss, but continuing restraint daily for 10 days did not increase weight loss because the rats adapted to the stress. In these two studies serum leptin, which suppresses the endocrine response to stress, was reduced in restrained rats. Peripheral infusion of leptin before and during restraint did not prevent stress-induced weight loss, although stress-induced corticosterone release was suppressed. Restrained rats were hyperthermic during restraint, but there was no evidence that fever or elevated free interleukin-6 caused the sustained reduction in weight. Restraining food-restricted rats caused a small but significant weight loss. Food-restricted rats fed ad libitum after the end of restraint showed a blunted hyperphagia and slower rate of weight regain than their controls. These results indicate that repeated acute stress induces a chronic change in weight independent of stress-induced hypophagia and may represent a change in homeostasis initiated by repeated acute activation of the central CRF system.

Activation of the hypothalamic arcuate nucleus predicts the anorectic actions of ciliary neurotrophic factor and leptin in intact and gold thioglucose-lesioned mice.

Similar to leptin, ciliary neurotrophic factor (CNTF) suppresses appetite and selectively reduces body fat in leptin-deficient ob/ob mice. To assess the relative importance of specific regions of the hypothalamus in mediating these effects, we administered a CNTF analogue (CNTFAx15) or leptin to mice made obese by administration of gold thioglucose (GTG), which destroys a well-defined portion of the medial basal hypothalamus. CNTFAx15 treatment reduced appetite and body weight in obese GTG-lesioned C57BL/6 mice, whereas leptin failed to effect similar changes regardless of whether treatment was initiated before or after the lesioned mice had become obese. Because leptin does not reduce food intake or body weight in most forms of obesity (a condition termed 'leptin resistance'), we also investigated the actions of leptin in GTG-lesioned leptin-deficient (ob/ob) mice. By contrast to C57BL/6 mice, leptin treatment reduced food intake and body weight in GTG-lesioned ob/ob mice, although the effect was attenuated. To further compare the neural substrates mediating the anorectic actions of leptin and CNTF, we determined the patterns of neurone activation induced by these proteins in the hypothalamus of intact and GTG-lesioned mice by staining for phosphorylated signal transducer and activator of transcription 3 (pSTAT3). CNTFAx15 stimulated robust pSTAT3 signalling in neurones of the medial arcuate nucleus in both intact and lesioned C57BL/6 and ob/ob mice. Leptin administration stimulated pSTAT3 signalling in only a few neurones of the medial arcuate nucleus in intact or lesioned C57BL/6 mice, but elicited a robust response in intact or lesioned ob/ob mice. By contrast to CNTFAx15, leptin treatment also resulted in prominent activation of STAT3 in several areas of the hypothalamus outside the medial arcuate nucleus. This leptin-induced pSTAT3 signal was at least as prominent in intact and GTG-lesioned C57BL/6 mice as it was in ob/ob mice, and thus was not correlated with appetite suppression or weight loss. These results indicate that the medial arcuate nucleus is a key mediator of appetite suppression and weight loss produced by CNTF and leptin, whereas GTG-vulnerable regions play a role only in leptin-induced weight loss. Other regions of hypothalamus in which pSTAT3 signal is induced by leptin may regulate energy metabolism through mechanisms other than appetite reduction.