Pituitary responsiveness to GH-releasing hormone, GH-releasing peptide-2 and thyrotrophin-releasing hormone in critical illness

OBJECTIVE Protein hypercatabolism and preservation of fat depots are hallmarks of critical illness, which is associated with blunted pulsatile GH secretion and low circulating IGF-I, TSH, T4 and T3. Repetitive TRH administration is known to reactivate the pituitary-thyroid axis and to evoke paradoxical GH release in critical illness. We further explored the hypothalamic-pituitary function in critical illness by examining the effects of GH-releasing hormone (GHRH) and/or GH-releasing peptide-2 (GHRP-2) and TRH administration. PATIENTS AND DESIGN Critically ill adults (n=40; mean age 55 years) received two i.v. boluses with a 6-hour interval (0900 and 1500 h) within a cross-over design. Patients were randomized to receive consecutively placebo and GHRP-2 (n=10), GHRH and GHRP-2 (n=10), GHRP-2 and GHRH+GHRP-2 (n=10), GHRH+GHRP-2 and GHRH+GHRP-2+TRH (n=10). The GHRH and GHRP-2 doses were 1μg/kg and the TRH dose was 200μg. Blood samples were obtained before and 20, 40, 60 and 120 minutes after each injection. MEASUREMENTS Serum concentrations of GH, T4, T3, rT3, thyroid hormone binding globulin (TBG), IGF-I, insulin and cortisol were measured by RIA; PRL and TSH concentrations were determined by IRMA. RESULTS Critically ill patients presented a striking GH response to GHRP-2 (mean±SEM peak GH 51±9 μg/l in older patients and 102±2μg/l in younger patients; P=0.005 vs placebo). The mean GH response to GHRP-2 was more than fourfold higher than to GHRH (P=0.007). In turn, the mean GH response to GHRH+GHRP-2 was 2.5-fold higher than to GHRP-2 alone (P=0.01), indicating synergism. Adding TRH to the GHRH+GHRP-2 combination slightly blunted this mean response by 18% (P=0.01). GHRP-2 had no effect on serum TSH concentrations whereas both GHRH and GHRH+GHRP-2 evoked an increase in peak TSH levels of 53 and 32% respectively. The addition of TRH further increased this TSH response < ninefold (P=0.005), elicited a 60% rise in serum T3 (P=0.01) and an 18% increase in T4 (P=0.005) levels, without altering rT3 or TBG levels. GHRH and/or GHRP-2 induced a small increase in serum PRL levels. The addition of TRH magnified the PRL response 2.4-fold (P=0.007). GHRP-2 increased basal serum cortisol levels (531±29nmol/l) by 35% (P=0.02); GHRH provoked no additional response, but adding TRH further increased the cortisol response by 20% (P=0.05). CONCLUSIONS The specific character of hypothalamic-pituitary function in critical illness is herewith extended to the responsiveness to GHRH and/or GHRP-2 and TRH. The observation of striking bursts of GH secretion elicited by GHRP-2 and particularly by GHRH+GHRP-2 in patients with low spontaneous GH peaks opens the possibility of therapeutic perspectives for GH secretagogues in critical care medicine.     

Decreased diet-induced thermogenesis in gluteal-femoral obesity

Resting metabolic rate (RMR) and diet-induced thermogenesis (DIT), induced by 100 g glucose given orally, were measured in two groups of obese women, characterized by the abdominal or gluteal-femoral type of obesity. No difference in RMR was found between the two groups. Obese women with an abdominal fat mass distribution have a higher and more prolonged DIT in comparison with gluteal-femoral obese women. This finding may help explain why women with upper body obesity are more able to lose weight than women with lower body obesity.     

Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme

BACKGROUND: Data on the effect of elective single embryo transfer (eSET) on the total and multiple pregnancy rates of an IVF/ICSI programme are reported. METHODS AND RESULTS: A retrospective cohort analysis of eSET was carried out over a 4 year period. A total of 1559 cycles resulted in 1464 transfers; 299 transfers of one top quality embryo (20.4%) and 86 of one non-top quality embryo (5.9%) yielded 149 conceptions (49.8%) with 105 ongoing pregnancies (35.1%) and 26 conceptions (30.2%) with 19 ongoing implantations (22.1%) respectively; 1079 transfers of two (n = 853; 58.3%) or more than two (n = 226; 15.4%) embryos yielded 366 ongoing pregnancies (33.9%). The ongoing pregnancy rates for the years between 1998 and 2001 were 35.9, 27.9, 31.9 and 31.0% per oocyte retrieval and 38.5, 29.4, 34.1 and 33.2% per transfer. There were no differences in pregnancy rates between any of the years. The average ongoing pregnancy rate (>12 weeks) over the 4 years was 31.5% per started cycle and 33.5% per transfer; the average number of embryos transferred decreased from 2.26 (1998) to 1.79 (2001); the multiple pregnancy and twinning rates dropped from 33.6 and 29.5% (1998) to 18.6 and 16.3% (2001) respectively. CONCLUSIONS: Judicious application of eSET can halve the twinning rate while maintaining the overall pregnancy rate.     

Cross-Sectional Associations between Mothers and Children’s Breakfast Routine—The Feel4Diabetes-Study

Positive influences of family members have been associated with a high probability of children’s daily breakfast consumption. Therefore, the aim of this study was to scrutinize the association of breakfast routines between mothers and their children. The baseline data of the Feel4Diabetes-study was obtained in 9760 children (49.05% boys)–mother pairs in six European countries. A parental self-reported questionnaire gauging the frequency of breakfast consumption and of breakfast´ foods and beverages consumption was used. Agreement in routines of mothers and their children’s breakfast consumption was analyzed in sex-specific crosstabs. The relationship of breakfast routine and food groups’ consumption between mothers and their children was assessed with analysis of covariance. The highest proportion of children who always consumed breakfast were those whose mothers always consumed it. Children consuming breakfast regularly had a higher intake of milk or unsweetened dairy products and all kind of cereal products (low fiber and whole-grain) than occasional breakfast consumers (p < 0.05). The strong similarity between mothers and children suggests a transfer of breakfast routine from mothers to their children, as a high proportion of children who usually consume breakfast were from mothers also consuming breakfast. All breakfast foods and beverages consumption frequencies were similar between children and their mothers.     

Magnesium and obesity: influence of gender, glucose tolerance, and body fat distribution on circulating magnesium concentrations.

Obesity is characterized by a high risk for glucose intolerance and cardiovascular disease. Since magnesium deficiency or depletion have often been associated with both pathologies, is of interest to study magnesium status in severely obese subjects before any form of treatment. Negative magnesium balances have been described in overweight persons submitted to total starvation, hypocaloric diets, and obesity surgery. For this reason 80 non-diabetic obese men and 118 age-matched obese women were studied. Serum and erythrocyte magnesium concentrations were significantly higher in the male population but the mean values were not suggestive of a magnesium deficit before any form of treatment was started. Since metabolic abnormalities and cardiovascular risk are greater in patients with upper body fat distribution (UBFD) both sexes were subdivided according to "waist-to-hip" circumference ratio. No difference could be shown in the obese men but in women, UBFD subjects showed higher basal insulin levels and increased erythrocyte magnesium concentration as compared to those with classical gynoid fat distribution. A 75 g oral glucose tolerance test enabled the subjects to be subdivided into those with normal or impaired glucose tolerance (IGT). The IGT group in both sexes was older and more obese. Mean values of serum magnesium and erythrocyte magnesium were not decreased despite the more pronounced insulin resistance in the IGT group. However a significant negative correlation was found between fasting blood sugar/insulinaemia and erythrocyte magnesium, showing that this middle-aged obese population can maintain normal circulating levels of magnesium, in contrast to type II diabetics or older subjects where for other reasons (urinary losses or decreased intake) magnesium status is interfered with.     

Surgical management of malignant melanoma using dynamic lymphoscintigraphy and gamma probe-guided sentinel lymph node biopsy: the Emory experience

Sentinel lymph node (SLN) biopsy is revolutionizing the surgical management of primary malignant melanoma. It allows accurate nodal staging which targets patients who may benefit from regional lymphadenectomy and systemic therapy. This is a retrospective review of patients treated at Emory University for stage I and II malignant melanoma with gamma probe-guided SLN biopsy from 1/1/94 to 6/30/98. Three hundred sixty patients (males 228, females 132) were identified. Primary melanoma sites included: head and neck 58, trunk 148, and extremities 154 (upper 71, lower 83). Primary tumor staging was T1 9, T2 134, T3 153, and T4 64. SLNs were successfully identified in 99.7 per cent of patients and 98.9 per cent of nodal basins mapped. In 275 (76.6%) cases a single draining nodal basin was identified. In 84 (23.3%) cases there were multiple draining nodal basins. Positive SLNs were identified in 63 patients (17.5%). SLN positivity by tumor staging was T1 0 per cent, T2 9.0 per cent, T3 22.2 per cent, and T4 26.6 per cent. The overall recurrence rate was 11.9 per cent. Recurrences by SLN status were SLN+, 27 per cent, and SLN-, 8.8 per cent. Regional recurrence occurred in 7 (2.4%) of the 297 with negative SLN biopsies and 7 (11.1%) of the 63 with positive SLN biopsies. Dynamic lymphoscintigraphy and gamma probe-guided SLN localization was successful in more than 98 per cent of cases. Patients with negative SLN biopsies have a low risk of recurrence.     

Validation of a finite element model of a unilateral external fixator in a rabbit tibia defect model

In case of large segmental defects in load-bearing bones, an external fixator is used to provide mechanical stability to the defect site. The overall stiffness of the bone–fixator system is determined not only by the fixator design but also by the way the fixator is mounted to the bone. This stiffness is an important factor as it will influence the biomechanical environment to which tissue engineering scaffolds and regenerating tissues are exposed. A finite element (FE) model can be used to predict the system stiffness. The goal of this study is to develop and validate a 3D anatomical FE model of a bone–fixator system which includes a previously developed unilateral external fixator for a large segmental defect model in the rabbit tibia. It was hypothesized that the contact interfaces between bone and fixator screws play a major role for the prediction of the stiffness. In vitro mechanical testing was performed in order to measure the axial stiffness of cortical bone from mid-shaft rabbit tibiae and of the tibia–fixator system, as well as the bending stiffness of individual fixator screws, inserted in bone. μCT-based case-specific FE models of cortical bone and SCREW–BONE specimens were created to simulate the corresponding mechanical test set-ups. The Young's modulus of rabbit cortical bone as well as appropriate screw–bone contact settings were derived from those FE models. We then used the derived settings in an FE model of the tibia–fixator system. The difference between the FE predicted and measured axial stiffness of the tibia–fixator system was reduced from 117.93% to 7.85% by applying appropriate screw–bone contact settings. In conclusion, this study shows the importance of screw–bone contact settings for an accurate fixator stiffness prediction. The validated FE model can further be used as a tool for virtual mechanical testing in the design phase of new tissue engineering scaffolds and/or novel patient-specific external fixation devices.