Physical activity intensity and type 2 diabetes risk in overweight youth: a randomized trial.

BACKGROUND: The chronic effects of high-intensity endurance training on metabolic health outcomes in overweight adolescents remains poorly understood. OBJECTIVE: To test the hypothesis that high-intensity endurance training (ET) is superior to moderate-intensity ET for improving risk factors for type 2 diabetes in overweight adolescents. DESIGN AND METHODS: In this randomized trial, 106 overweight and obese adolescents (15.2 years; 76% female; 62% Caucasian) were randomly assigned to high-intensity ET (70-85% of heart rate reserve, n=38), moderate-intensity ET (40-55% heart rate reserve; n=32) or control for 6 months (n=36). The primary and secondary outcome measures were insulin sensitivity assessed using a frequently sampled intravenous glucose tolerance test and hepatic triglyceride content with magnetic resonance spectroscopy. Exploratory outcomes were cardiorespiratory fitness, physical activity and MRI and dual x-ray absorptiometry-derived measures of adiposity. RESULTS: The study had 96% retention and attendance was 61±21% and 55±24% in the high- and moderate-intensity ET arms. Intention-to-treat analyses revealed that, at follow-up, insulin sensitivity was not different between high-intensity (-1.0 mU kg(-1) min(-1); 95% confidence interval (CI): -1.6, +1.4 mU kg(-1) min(-1)) and moderate-intensity (+0.26 mU kg(-1) min(-1); 95% CI: -1.3, +1.8 mU kg(-1) min(-1)) ET arms compared with controls (interaction, P=0.97). Similarly, hepatic triglyceride at follow-up was not different in high-intensity (-1.7% fat/water (F/W); 95% CI: -7.0, +3.6% F/W) and moderate-intensity (-0.40% FW; 95% CI: -6.0, +5.3% F/W) ET compared with controls. Both high intensity (+4.4 ml per kg-FFM (fat-free mass) per minute; 95% CI: 1.7, 7.1 ml kg-FFM(-1) min(-1)) and moderate intensity (+4.4 ml kg-FFM(-1) min(-1); 95% CI: 1.6, 7.3 ml kg-FFM(-1) min(-1)) increased cardiorespiratory fitness, relative to controls (interaction P<0.001). CONCLUSIONS: ET improves cardiorespiratory fitness among obese adolescents; however, owing to lack of compliance, the influence of exercise intensity on insulin sensitivity and hepatic triglycerides remains unclear.

Risk factors of postoperative vomiting in children receiving continuous intravenous morphine.

BACKGROUND: Risk factors of postoperative vomiting (POV) have been less extensively explored in children compared to adults. We analyzed the risk factors of POV in children receiving continuous intravenous (i.v.) morphine in a standardized manner without POV prophylaxis after major surgery. METHODS: This observational retrospective study included 235 children aged from 2 to 216 months (91 F:144 M, 11.5% <6 months, 31.5% 6-11 months). The primary end point was the occurrence of at least one episode of POV recorded on the nursing chart. The independent predictors of POV were determined by univariate analysis followed by a multivariate analysis by logistic regression. The data are presented as either medians (25th-75th percentile) or as values with a 95% confidence interval. RESULTS: Continuous i.v. morphine was administered over 42 (22-60) h with an initial infusion rate of 20 µg x kg(-1) x h(-1) in 63% of cases, which was increased in 31.5% of cases and was accompanied by an additional bolus in 39.2% of children. At least one episode of POV occurred in 22.6% of children. The following three independent factors were associated with POV: female gender (OR 3.324 [1.695-6.519], P=0.0005), urological surgery (OR 5.605 [1.291-24.340], P=0.0214) and age (OR 1.012 [1.006-1.018], P<0.0001). The discriminating characteristics of the model were good with an ROC curve AUC of 0.778, sensitivity of 71.7% and specificity of 71.4% for a 0.22 cut-off value of POV incidence. The positive predictive value was 42.2%, and the negative predictive value was 89.6%. CONCLUSION: Female gender, which is usually considered a risk factor after puberty, should be taken into account independent of age to guide the POV prophylaxis in children receiving a postoperative continuous i.v. morphine infusion.

CYP2D7-2D6 hybrid tandems: identification of novel CYP2D6 duplication arrangements and implications for phenotype prediction.

AIMS: Allelic variants of cytochrome P450 CYP2D6 (CYP2D6), such as gene deletion, duplication, multiplication and conversion, contribute to the wide range of CYP2D6 activity. Novel gene arrangements were discovered and characterized. MATERIALS & METHODS: DNA from 32 Caucasian and 59 African-American duplication-positive subjects were analyzed by long-range PCR and genotyping to detect CYP2D7-2D6 hybrid tandem alleles. Novel allelic variants were sequenced and a strategy for the detection and analysis of hybrid genes was refined. RESULTS: CYP2D7-2D6 hybrid tandem alleles were identified in one African-American and four Caucasian subjects. Three novel hybrid genes were found on CYP2D6*1 and CYP2D6*2 duplication backgrounds and designated CYP2D6*76, *77 and *78. CYP2D7 to 2D6 conversion occurred in introns 1 and 4, and exon 9. All carried a T-insertion in exon 1 abolishing activity. In Caucasians, four out of 33 (12%) of the duplication-positive alleles were hybrid tandems, three CYP2D6*77 + *2 and one CYP2D6*78 + *2. By contrast, in African-Americans only one of 60 duplication-positive alleles was identified as a hybrid tandem. This allele was designated CYP2D6*76 + *1. CONCLUSION: Hybrid tandem alleles occur infrequently (<0.25%) in Caucasians, but may explain why not every subject with a CYP2D6 duplication presents with an ultrarapid metabolizer phenotype.

[Body mass index and albuminemia in patients under mechanical circulatory assistance before cardiac transplantation]. / Indice de masse corporelle et albuminémie péri-implantatoires de patients sous assistance circulatoire mécanique (ACM) en attente d'une transplantation cardiaque.

OBJECTIVE: To evaluate the prognostic influence of peri-implantation nutritional status of patients under mechanical circulatory assist (MCA) prior to cardiac transplantation (CT). STUDY DESIGN: Retrospective analysis of patients with cardiogenic shock included from June 1997 to December 2002. PATIENTS AND METHODS: Evaluation at MCA's implantation, at day (D) 30 and at CT or patient's death (D) of body mass index (BMI=body weight (kg)/size (m(2)), albuminemia (Alb g/l), expressed as median values (med) and range (min-max). Odds ratio (OR) and CI 95%) were calculated. A multivariate analysis was performed to determine variables related to D or CT success. RESULTS: Thirty-four patients (30 men), median age 40.5 years (10-63), were included. MCA types were cardiac pumps (N=3); pneumatic (N=18) or electric (N=5) ventricular assist devices and artificial heart (N=8). Global mortality was 56% (19 over 34 patients) and at implantation in the global population (N=34) BMI was 19.4 (9.3-28.1) and Alb 24.6 g/l (15-37.5). At MCA's implantation and D30 respectively, 38 and 42% of the patients had a severe hypoAlb (Alb<30 g/l) and a BMI<19 attesting of a seriously deteriorated nutritional status. No significant statistical difference was observed on median BMI of transplanted patients T (N=15) and expired patients D (N=19). Alb was significantly different (p<10(-4)) between T and D patients: median Alb: 30 g/l (20-37.5) in T patients, 20 g/l (15-31) in D patients. HypoAlb<21 g/l was an independent prognostic factor of death (p=0.004; OR: 0.541; IC95% : 0.36-0.82) and Alb>33 g/l an independent prognostic factor of CT success (p=0.003; OR:1.38; IC95% : 1.12-1.71). CONCLUSION: These results seem to demonstrate that at MCA implantation, a seriously deteriorated albuminemia level (<30 g/l) negatively impacts patients overall survival after CT.

Facilitating access to glucometer reagents increases blood glucose self-monitoring frequency and improves glycaemic control: a prospective study in insulin-treated diabetic patients.

AIMS: To investigate whether availability of glucometer reagents increases the frequency of self-blood glucose monitoring (SBGM) and improves glycaemic control in diabetic patients. METHODS: Sixty-two insulin-treated diabetic patients were randomized to two groups, matched for age, gender, education, income, type and duration of diabetes, years of insulin treatment, number of daily insulin injections, and haemoglobin (Hb)A1c. All patients were given a glucometer, but one group (no cost, NC) was provided glucometer test strips free of charge. The other group (control, C) had to purchase strips as they found it necessary. Both groups of patients were followed longitudinally at 2-monthly intervals for 12 months with measurement of blood glucose and HbA1c, and the frequency of SBGM was determined by downloading the glucometer memory. RESULTS: The SBGM frequency was significantly higher in the NC group vs. the C group during the first 4 months (2.0 +/- 0.2 tests/day vs. 1.4 +/- 0.1 tests/day, P<0.025). Mean HbA1c remained stable over the 12 months in the NC group, whereas an increase with time was observed in the C group. The difference in HbA1c between the two groups was significant (P<0.002) after 6 months. Random blood glucose measured at each visit and average glucose recorded by the glucometer were also lower in the NC group vs. the C group (P<0.005). There was a negative correlation between HbA1c and SBGM frequency, and HbA1c in patients testing at least twice a day was lower than in those testing less than twice a day (8.8 +/- 0.2% vs. 9.6 +/- 0.2%, P<0.001). CONCLUSIONS: In this prospective study, having easy access to glucometer strips provided free of charge to patients increased SBGM frequency. The relationship between HbA1c and SBGM frequency supports the view that SBGM is an essential tool in diabetes management.

Postoperative epidural analgesia with bupivacaine and fentanyl: hourly pain assessment in 348 paediatric cases.

BACKGROUND: The objective of this prospective study was the evaluation of the analgesia provided by an epidural infusion of bupivacaine and fentanyl after different types of surgery in children. METHODS: Data were collected from 348 epidural analgesia in 87 children below 2 years of age, in 80 children between 2 and 6 years and 181 above 6 years of age, for a median duration of 43 postoperative hours. Bupivacaine (mean concentration 0.185%) and fentanyl (5 microg.kg-1.day-1) were administered on the surgical ward. RESULTS: Pain control was considered excellent in 86% of the 11 072 pain hourly assessments. Analgesia was found to be better for children older than 2 years, and the overall quality of their night's sleep was better than that of older children. Higher pain scores were noted for Nissen fundoplication surgery and club foot repairs. Early discontinuation rarely occurred, and only because of technical problems with the epidural catheter (4%) or insufficient analgesia (6%). Complications were minor (nausea/vomiting 14%, pruritus 0.6%, urinary retention 17%) and easily reversed. CONCLUSIONS: This combination of bupivacaine-fentanyl provides safe analgesia after major surgery in children with frequent clinical monitoring. Regular pain assessments of intensity and duration are useful to improve the quality of postoperative analgesia.

Relationship between serum leptin and the insulin-like growth factor-I system in humans.

The growth hormone (GH)/insulin-like growth factor-I (IGF-I) system and leptin both play an important role in the regulation of body composition. Although the regulation of these two hormonal systems by insulin has been under intense investigation, the physiologic interactions between leptin and the GH/IGF-I system remain unknown. In this study, we examined the relationships among circulating leptin and key elements of the IGF-I system in 60 subjects (27 nondiabetic lean, 21 nondiabetic obese, and 12 type 1 diabetic subjects) with a wide range of insulin secretory capacity. Leptin, glucose, insulin, free IGF-I, total IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured in the basal state after an overnight fast, and the acute insulin response to glucose (AIRG) was determined after intravenous glucose injection. AIRG was significantly higher (P < .01) in the obese (3,365+/-562 pmol/L x min) versus lean subjects (1,624+/-155 pmol/L x min). In simple regression analysis, the serum leptin concentration was positively correlated with the body mass index ([BMI] men, r = .51, P = .005; women, r = .71, P < .001), IGFBP-3 (men, r = .20, P = nonsignificant; women, r = .41, P < .025), and AIRG (men, r = .73, P < .001; women, r = .62, P < .01). There was a nonlinear correlation between leptin and IGFBP-1, but there was no correlation between leptin and free or total IGF-I. In multiple regression analysis with leptin as the dependent variable, gender, BMI, and IGFBP-3 entered the equations at a statistically significant level. The correlation of leptin with IGFBP-3 was independent of obesity and persisted after correction for AIRG, suggesting a link between leptin and GH action.

Free insulin-like growth factor I (IGF-I) in healthy subjects: relationship with IGF-binding proteins and insulin sensitivity.

The majority of insulin-like growth factor I (IGF-I) circulates in blood bound to a family of IGF-binding proteins (IGFBPs). Only a small fraction of IGF-I is unbound or free, and one of the postulated roles of the IGFBPs is regulation of this free component, thereby increasing IGF-I bioavailability. Whether free IGF-I plays a physiological role in glucose homeostasis, however, is not clear. In this study, we examined the effects of acute changes in serum insulin on free IGF-I, total IGF-I, IGFBP-1, and IGFBP-3 in 11 healthy subjects. Glucose (0.3 g/kg) and insulin (0.05 U/kg) were injected iv at 0 and 20 min, respectively. Blood samples were drawn at defined intervals for 3 h, and insulin sensitivity (SI) was computed by Bergman's minimal model. Serum insulin reached a first peak after glucose injection and a second, higher peak after exogenous insulin administration. Although the total IGF-I level remained constant for the duration of the experiment, free IGF-I decreased by 20% 20 min after the first insulin peak and by 35% 20 min after the second peak. IGFBP-1 first declined to 20% below basal, then rose to 3-fold the basal level. IGFBP-3 increased linearly to 20% above basal by the end of the experiment, and this increase mirrored the decline of free IGF-I. In the fasting state, free IGF-I was positively correlated with SI (r = 0.52; P < 0.005) and inversely correlated with glucose (r = -0.51; P < 0.005) and IGFBP-1 (r = -0.65; P < 0.001). In conclusion, free IGF-I is acutely regulated by insulin and correlates with SI, suggesting that it may play a physiological role in glucose homeostasis.

Absence of serologic evidence for hepatitis C virus infection in patients with Hashimoto's thyroiditis.

BACKGROUND/AIMS: This paper explores the reported association between Hashimoto's thyroiditis and hepatitis C virus (HCV) infections. MATERIALS AND METHODS: The results of serologic testing for anti-HCV antibody levels were documented in 28 patients (19 female, 9 male) with Hashimoto's thyroiditis and 23 age and gender matched controls with non-Hashimoto's thyroid disorders. RESULTS: The anti-HCV results were negative in both groups. CONCLUSIONS: These findings suggest that despite a reported high prevalence of Hashimoto's thyroiditis in patients with chronic HCV infections, the reverse is not true and hence routine anti-HCV screening cannot be advocated for patients with Hashimoto's thyroiditis.

Constitutive expression of a somatic heat-inducible hsp70 gene during amphibian oogenesis.

We isolated and characterized a sequence coding for heat-shock protein 70 (HSP70) of the amphibian Pleurodeles waltl. Results from S1 nuclease protection assays led us to conclude that an hsp70 gene, strictly inducible in somatic cells during heat shock, is constitutively active during oogenesis. By quantitative northern and western blot analysis, we showed that both hsp70 mRNA and HSP70-related protein levels increased in oocytes from stage II to stage VI under physiological conditions. Furthermore, by in situ hybridization to the nascent transcripts of lampbrush chromosome loops, we provided evidence for a clear-cut relationship between this increase in hsp70 mRNA and transcriptional activity during the lampbrush stage of oogenesis. These results strongly suggest that hsp70 genes are actively transcribed throughout oogenesis. HSP70-related proteins localized in the cytoplasm of young oocytes are progressively transferred to the nucleus in the course of oogenesis and preferentially accumulated in the nuclei of some stage VI oocytes.

Evolution de la situation nutritionnelle dans un contexte d'ajustement structurel en milieu urbain au Congo

Cette enquete nutritionnelle a ete realisee a Brazzaville. Les resultats preliminaires de l'enquete mettent en evidence une evolution contrastee de la situation nutritionnelle depuis 1986 selon l'indicateur considere. On observe en effet peu de variation au niveau du retard de taille a l'exception des classes d'age comprises entre 18 et 24 mois. Durant cette periode; une nette regression a ete relevee. Par contre; la prevalence de maigreur s'est accentuee pour les classes allant jusqu'a 24 mois. Cette aggravation se retrouve au niveau des poids de naissance inferieurs a 2500g; leur frequence s'est accentuee. D'autre part; la valeur du poids moyen a la naissance a diminue. Parallelement a cette evolution; l'etat nutritionnel des meres s'est modifie. Les prevalences de maigreur et d'obesite ont augmente traduisant une degradation sensible de la situation depuis 1986 qui a pu jouer sur l'etat de sante des jeunes enfants