Adult height and health-related quality of life after growth hormone therapy in small for gestational age subjects.

OBJECTIVE: To estimate health-related quality of life (HRQoL) in non-growth hormone deficient (GHD) small for gestational age (SGA) children before and after growth hormone (GH) treatment to adult height (AH). METHODS: This was a multicentre, two-arm trial. Following an initial 2-year double-blind study period, patients entered a 2-year extension period followed by treatment to AH. At baseline patients were randomised to GH (0.033 or 0.067 mg/kg/day) and continued treatment at that dose until AH. Height was assessed at baseline and 3-monthly intervals to AH (height velocity <2 cm/year). Height standard deviation score (SDS) before and after GH therapy was mapped onto estimated HRQoL scores up to AH. RESULTS: Of the 79 children randomised into the study 53 were non-GHD (defined as peak GH >20 mU/L [peak 24-h GH value and peak arginine tolerance test]). At baseline these children had a mean (mean [+/-SD]) height SDS of -3.2 (0.7), height velocity SDS -0.6 (1.2) and age, 8.1 (1.9) years. Estimated HRQoL scores were significantly (p < 0.001) increased from baseline at AH (ΔHRQoL, 95% CI) (0.033 mg/kg/day, 0.112 [0.092, 0.132]; 0.067 mg/kg/day, 0.115 [0.094, 0.136]). HRQoL was not different between treatment groups. A significant gain in AH, relative to an SGA reference population, was reported in GH-treated patients. Mean (95% CI) ΔAH SDS (0.033 mg/kg/day, +1.4 [1.1, 1.6]. 0.067 mg/kg/day, +1.7[1.4, 2.0]). LIMITATIONS: The analysis assumes HRQoL can be mapped onto height SDS. CONCLUSIONS: GH treatment in short children born SGA without signs of persistent catch-up growth was associated with significant improvement in HRQoL and normalisation of AH.

Effects of a 3-day fast on regional lipid and glucose metabolism in human skeletal muscle and adipose tissue.

AIM: Fasting is characterized by increased whole body lipolysis and lipid oxidation, decreased glucose oxidation and insulin resistance. To identify the regional sources and underlying mechanisms, we studied 10 healthy male volunteers post-absorptively and after 72 h of fasting. METHODS: Each study comprised a 3-h basal period and a 3-h hyperinsulinaemic euglycaemic clamp and we used a combination of leg and forearm arteriovenous techniques, upper and lower body microdialysis and glucose and palmitate tracers. RESULTS: In the basal state, plasma levels, fluxes and oxidation rates of free fatty acids all roughly doubled after fasting. Palmitate fluxes across the forearm and leg also increased by two to threefold and interstitial leg muscle glycerol concentrations doubled. Subcutaneous femoral glycerol concentrations and blood flows were unaltered, but abdominal subcutaneous blood flow increased by 50% in the presence of unchanged glycerol concentrations, indicating stimulated abdominal lipolysis. During the clamp, we observed whole body insulin resistance and glucose uptake across the leg and forearm decreased by 60%. CONCLUSION: Our data show that fasting induces insulin resistance in upper and lower body muscles and suggest that increased lipolysis, is primarily due to the activation of lipolysis in muscle-associated fat (in the leg) and in upper body subcutaneous fat, whereas peripheral subcutaneous fat is spared.

An evaluation of the relationship between adult height and health-related quality of life in the general UK population.

OBJECTIVE: Short stature has previously been shown to influence several social factors during childhood and adult life. However, limited data exist to determine the influence of short stature on health-related quality of life (HRQoL) because of underpowered studies and the fact that children find questionnaires very difficult to complete. The objective of this study was to examine the influence of height on HRQoL for the general adult population in the UK. DESIGN: The 2003 Health Survey for England (HSE03), commissioned by the Department of Health, provides a random general population sample for the population living in private households in England. Observations for 14 416 adults (aged > 18 years) were included in the analysis. MEASUREMENTS: The survey involved a questionnaire-based interview and a nurse visit, where measurements and blood samples were taken. HRQoL was measured using the EQ-5D questionnaire. Social class (I-V) was derived according to definitions from UK National Statistics. Height was converted from centimetres to height standard deviation scores (HSDS). RESULTS: Mean EQ-5D scores were lower in subjects with greater height deficit than in taller subjects. Three significantly different subgroups were identified using an analysis of variance (anova). The first subgroup 'HSDS HSDS 0'. Multivariate linear regression analysis showed significant correlations between height and HRQoL, such that an increase in height of 1 HSDS predicts an improvement in EQ-5D score of 6.1% for subjects shorter than -2.0 HSDS. Social class was a significant predictor of HRQoL in taller, but not in shorter, subjects. CONCLUSION: The results of this study demonstrate that height in adult life is correlated with HRQoL and that short stature in adult life may be associated with a significant reduction in HRQoL.

Additive effects of cortisol and growth hormone on regional and systemic lipolysis in humans.

Growth hormone (GH) and cortisol are important to ensure energy supplies during fasting and stress. In vitro experiments have raised the question whether GH and cortisol mutually potentiate lipolysis. In the present study, combined in vivo effects of GH and cortisol on adipose and muscle tissue were explored. Seven lean males were examined four times over 510 min. Microdialysis catheters were inserted in the vastus lateralis muscle and in the subcutaneous adipose tissue of the thigh and abdomen. A pancreatic-pituitary clamp was maintained with somatostatin infusion and replacement of GH, insulin, and glucagon at baseline levels. At t = 150 min, administration was performed of NaCl (I), a 2 microg.kg(-1).min(-1) hydrocortisone infusion (II), a 200-microg bolus of GH (III), or a combination of II and III (IV). Systemic free fatty acid (FFA) turnover was estimated by [9,10-3H]palmitate appearance. Circulating levels of glucose, insulin, and glucagon were comparable in I-IV. GH levels were similar in I and II (0.50 +/- 0.08 microg/l, mean +/- SE). Peak levels during III and IV were approximately 9 microg/l. Cortisol levels rose to approximately 900 nmol/l in II and IV. Systemic (i.e., palmitate fluxes, s-FFA, s-glycerol) and regional (interstitial adipose tissue and skeletal muscle) markers of lipolysis increased in response to both II and III. In IV, they were higher and equal to the isolated additive effects of the two hormones. In conclusion, we find that GH and cortisol stimulate systemic and regional lipolysis independently and in an additive manner when coadministered. On the basis of previous studies, we speculate that the mode of action is mediated though different pathways.

Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans.

Cortisol's effects on lipid metabolism are controversial and may involve stimulation of both lipolysis and lipogenesis. This study was undertaken to define the role of physiological hypercortisolemia on systemic and regional lipolysis in humans. We investigated seven healthy young male volunteers after an overnight fast on two occasions by means of microdialysis and palmitate turnover in a placebo-controlled manner with a pancreatic pituitary clamp involving inhibition with somatostatin and substitution of growth hormone, glucagon, and insulin at basal levels. Hydrocortisone infusion increased circulating concentrations of cortisol (888 +/- 12 vs. 245 +/- 7 nmol/l). Interstitial glycerol concentrations rose in parallel in abdominal (327 +/- 35 vs. 156 +/- 30 micromol/l; P = 0.05) and femoral (178 +/- 28 vs. 91 +/- 22 micromol/l; P = 0.02) adipose tissue. Systemic [(3)H]palmitate turnover increased (165 +/- 17 vs. 92 +/- 24 micromol/min; P = 0.01). Levels of insulin, glucagon, and growth hormone were comparable. In conclusion, the present study unmistakably shows that cortisol in physiological concentrations is a potent stimulus of lipolysis and that this effect prevails equally in both femoral and abdominal adipose tissue.

Motion correction for the quantification of mitral regurgitation using the control volume method.

Quantifying mitral regurgitation is difficult because of the complexity of the flow, geometry and motion of the mitral valve. In this paper a MRI compatible phantom was built incorporating a left ventricle and mitral valve motion. Valve motion was obtained using a pneumatic piston. The mitral valve was made regurgitant and the regurgitant volume quantified using a modified control volume method. The modification to the method was the addition of mitral motion correction. This was attained by moving the control volume in unison with the mitral valve and by correcting for this motion in the integration of velocity. This correction was found to be simple, in that it represented the volume swept out by the moving control surface. The measured regurgitant volume was compared to a second MR measurement using a single slice technique, made possible by the tubular construction of the phantom's left atrium. Regression analysis between these two methods produced a regression line of y = 0 + 1.02 x; R = 0.97; standard error of the estimate = 3.47 ml.

High-resolution assessment of velocity fields and shear stresses distal to prosthetic heart valves using high-field magnetic resonance imaging.

BACKGROUND AND AIM OF THE STUDY: Complications after replacement of diseased heart valves with mechanical prostheses have been shown to be related to the hemodynamics distal to the valve. For this reason, the velocity patterns have been disclosed in vitro with a variety of different techniques. This study introduces a magnetic resonance imaging (MRI) -based technique, which entails easy acquisition of fluid velocity field data with a high accuracy and spatial resolution. METHODS: A high-field magnetic resonance scanner equipped with short echo time phase-contrast velocity measurement software was applied in a detailed mapping of the axial velocity profile across the entire vessel area at two positions downstream of a bileaflet valve prosthesis inserted in a pulsatile flow system in vitro. The laminar shear forces were calculated from the fluid velocity field data. RESULTS: The velocity profiles very close to the valve reflected the bileaflet design as also shown in previous studies, but the extent and velocities of the jet emanating from the slit between the leaflets were clearly better visualized. However, one diameter downstream of the valve the central jet was completely dispersed and the hemodynamic complexity was significantly reduced. Recirculation and retrograde flow regions that might be relevant for understanding typical long-term complications after implantation were observed close to the valve. CONCLUSIONS: In one scan experiment the presented method provides information on flow characteristics that previously required application of different types of experiment. Thus, the method seems promising as a new technique for detailed and extensive mapping of the velocities and laminar shear stresses downstream of prosthetic heart valves in vitro.

In vivo analysis of dynamic tensile stresses at arterial end-to-end anastomoses. Influence of suture-line and graft on anastomotic biomechanics.

OBJECTIVE: to determine the influence of an anastomotic suture line and a graft on dynamic tensile stresses of vascular end-to-end anastomoses in vivo. MATERIAL AND METHODS: the abdominal aorta of twelve 35-kg pigs was used as an experimental model. Simultaneous recordings of internal arterial diameter and pressure were performed on each pig at 3 successive stages: (1) The genuine artery (REF), (2) artery-artery (A-A) and (3) graft-artery (G-A) anastomosis at 1-mm increments in the immediate perianastomotic area. Thereby, RD (relative distension), CC (compliance coefficient), E(p)(dynamic pressure-strain elastic modulus) and hysteresis loop areas could be calculated for every measuring point. RESULTS: the graft was significantly stiffer than REF. A-A and G-A anastomoses were significantly less compliant than REF. Maximum E(p), minimum CC and hysteresis loop areas were found at the anastomotic line due to minimum anastomotic RD. Downstream of the G-A anastomosis, the RD, CC, E(p)and loop areas were significantly different from REF, but significantly different from A-A. CONCLUSION: an animal model for acute studies of mechanical properties of vascular end-to-end anastomoses was developed. The main determinant for anastomotic biomechanics was the suture-line itself.

Endoscopic sclerotherapy in porcine esophagus changes luminal cross-sectional area and wall distensibility dose- and time-dependently.

The dose- and time-dependent effects of endoscopic sclerotherapy on luminal cross-sectional area and wall distensibility were studied in pigs at 5 and 12 cm proximal to the gastroesophageal junction by means of impedance planimetry. Sixteen healthy animals underwent two sessions of endoscopic sclerotherapy two weeks apart with injections of either 5 or 10 ml of 1% Polidocanol in the distal 7 cm of the esophagus each time. The animals were investigated before sclerotherapy, two weeks after each session, and finally six weeks after the last session. Six healthy animals were studied as controls. Endoscopic sclerotherapy caused luminal narrowing in the sclerosed zone followed by normalization six weeks after the last treatment (P < 0.05 in both groups). Wall distensibility decreased in the sclerosed zone after treatment with 10 ml sclerosant (P < 0.05) followed by partial normalization, while no effect was found after 5 ml sclerosant (P > 0.2). Progressive dilations were observed in the proximal esophagus in both groups and were most pronounced in the 10 ml group (P < 0.05). Wall distensibility did not change proximal to the site of sclerotherapy in either group (P > 0.1).

Arteriovenous fistulas aggravate the hemodynamic effect of vein bypass stenoses: an in vitro study.

PURPOSE: The purpose of this study was to assess the impact of arteriovenous fistulas combined with varying degrees of stenosis on distal bypass hemodynamics and Doppler spectral parameters. METHODS: In an in vitro flow model bypass stenoses causing 30%, 55%, and 70% diameter reduction were induced 10 cm upstream of a fistula with low outflow resistance. Flow and intraluminal pressure were measured proximal to the stenosis and downstream of the fistula. The waveform parameters peak systolic velocity, end-diastolic velocity, pulsatility index, and pulse rise time were determined from midstream Doppler spectra obtained 10 cm downstream of the fistula. All measurements were carried out with open and clamped fistula. RESULTS: At 30% diameter reducing stenosis opening of the fistula induced a 12% systolic pressure drop across the stenosis but had no adverse effect on the Doppler waveform parameters. At 55% stenosis the pressure drop increased from 16% to 31% after fistula opening. This increased pressure drop was associated with a further reduction in peak systolic velocity, a decrease in pulsatility index, and an enhanced pulse rise time prolongation. Fistula opening at 70% stenosis increased the systolic pressure drop from 31% to 48% and had significant impact on all waveform parameters. CONCLUSIONS: Distal arteriovenous fistulas enhance pressure loss across stenoses and affect downstream velocity waveform configuration. The presence of a combined fistula and a stenosis mimics the distal hemodynamic conditions of a more severe stenosis. Assessment of the hemodynamic impact of fistulas must be undertaken in the evaluation of in situ vein bypass stenoses.

Monitoring thrombin generation with prothrombin fragment 1.2 assay during cardiopulmonary bypass surgery.

UNLABELLED: Despite high plasma levels of heparin during cardiopulmonary bypass surgery, activation of the coagulation system has been reported. We hypothesize that the coagulation system activity most appropriately could be assessed by molecular markers of thrombin generation. The aim of the present study was to describe the changes in thrombin generation during CPB, using prothrombin fragment F1 + 2 (F1.2) as an indicator and evaluate different blood sampling regimens for interpretation of the F1.2 measurements. Twenty patients, operated under extracorporeal circulation with coronary artery bypass grafting (CABG), comprised the study material. The heparin levels were maintained above 2.5 IU/ml throughout the bypass procedure and the functional AT-III level was kept above 0.5 U/ml. Despite of this anticipated inactivation of the coagulation system, the concentrations of F1.2 and FpA increased throughout CPB, particularly after release of the aortic crossclamp. F1.2 and FpA correlated significantly (R = 0.69). No statistically significant correlation was found between F1.2 formation rate and age, bodyweight, baseline ACT, ACT after 200 IU heparin/kg, average heparin concentration during CPB or average AT-III level during CPB. CONCLUSIONS: Thrombin formation seems to be a continuous process during CPB despite adequate heparinization. The pattern of thrombin generation can be assessed most appropriately in terms of F1.2 generation rate. Extraordinary high levels of F1.2 were seen after release of the aortic crossclamp, indicating that the periods before and after aortic crossclamping should be evaluated separately.