Two cases of "stone heart" with fatal outcome.

The "stone heart" syndrome is a rare but often fatal complication of cardiac surgery associated with hypertrophy of the myocardium. The mechanisms behind the syndrome are not fully understood. In this case report, we describe two cases of stone heart in newborn girls. Both girls were born with congenital heart abnormalities including ventricular septum defects (VSD), hypertrophy of the myocardium and patent arterial duct (PDA), which was prenatally diagnosed. In each of the two cases, the stone heart became evident immediately after initiating cardiopulmonary bypass, and ended fatally.

Family-centred care and traumatic symptoms in parents of children admitted to PICU.

BACKGROUND: Studies show that traumatic stress symptoms are common in parents of children admitted to the pediatric intensive care unit (PICU). Family-centred care (FCC) has shown promising potential in reducing levels of traumatic stress in this group of parents. OBJECTIVES: To investigate the association between parents' experience of nursing care and levels of traumatisation, to identify potential gender differences within this group, and to examine the possible relationships among the severity of a child's illness, the parents' fear of losing their child, and the parents' experience of support and development of acute stress disorder (ASD) symptoms. ETHICAL ISSUES/APPROVAL: This study was approved by The Central Denmark Regional Committee on Health Research Ethics and by the Danish Data Agency (#1-16-02-87-11) and data were stored, protected and destroyed according to their regulations. METHODOLOGY/DESIGN: This cross-sectional study involved 90 parents of children admitted to PICU at the University Hospital of Aarhus from August 2011 to August 2012. The parents filled out a self-report questionnaire package at the time of their child's discharge from the hospital. RESULTS: The experience of support from the nurses was high in both parents and was associated with ASD. About one-third of the parents had ASD or subclinical ASD. No significant gender differences existed when symptoms were measured dimensionally. When measured categorically, 17% of the mothers and 7% of the fathers had ASD. Mothers with very young children had higher levels of acute stress; fathers whose children had high illness severity scores exhibited more acute stress. STUDY LIMITATIONS: Limitations have been identified in relation to the sample size of the study, the cross-sectional design and the short amount of time the families were in contact with PICU. CONCLUSION: The fathers and mothers were very pleased with the perceived care at the unit. The experienced care was positively associated with acute stress, but not with illness severity, or fear of losing the child. More research is needed to understand the dynamics of family-centred care.

Face validity and inter-rater reliability of the Danish version of the modified Yale Preoperative Anxiety Scale.

INTRODUCTION: Preoperative anxiety is common in children and it is associated with an adverse post-operative outcome. The modified Yale Preoperative Anxiety Scale (m-YPAS) was developed to assess preoperative anxiety in children. The purpose of this study was to translate and adapt the m-YPAS to Danish cultural and linguistic conditions and to test its face validity and inter-rater reliability in a clinical setting. MATERIAL AND METHODS: Translation was done in accordance with the WHO guidelines. Face validity and linguistic challenges were resolved in a focus group with five nurse anaesthetists. Inter-rater reliability for the subscales in the m-YPAS was determined at two different time points by using weighted kappa (κw) statistics, whereas agreement on the overall weighted scores was calculated using the intraclass correlation coefficient (ICC). The inter-rater reliability test was done by a paediatric anaesthesiologist consultant, a psychiatrist and the first author. RESULTS: The Danish version of the m-YPAS was considered suitable and its face validity was satisfactory. Inter-rater reliability analysis revealed that inter-observer agreement among three independent raters was good (induction 1: κw: 0.63-0.98, ICC = 0.92; induction 2: κw: 0.72-0.96, ICC = 0.92). CONCLUSION: Standardised and validated assessment tools are needed to evaluate interventions to reduce preoperative anxiety in children. A Danish version of the m-YPAS now exists, and preliminary testing has demonstrated a satisfactory face validity and inter-rater reliability. FUNDING: The study was supported by grants from TrygFonden (Grant number: j.no.7-11-1292). TRIAL REGISTRATION: The Danish Data Protection Agency, the Central Denmark Region, has approved the study (j.no.: 2007-58-0010).

Muscle GLUT4 in cirrhosis.

BACKGROUND/AIMS: The insulin-dependent glucose transporter GLUT4 mediates 50-80% of whole body glucose uptake, but its relation to the frequent glucose intolerance in patients with liver cirrhosis is unknown. METHODS: Thirty patients and seven healthy controls underwent a 2-h oral glucose tolerance test and later a muscle biopsy. Levels of GLUT4 total protein and mRNA content were determined in muscle biopsies by polyclonal antibody labelling and RT-PCR, respectively. RESULTS: GLUT4 protein content in the cirrhosis group was not different from that of the controls, but at variance with the control subjects it correlated closely with measures of glucose tolerance (R(2)=0.45; p=0.003). GLUT4 mRNA of the patients with cirrhosis was reduced to 56% of control value (95% ci: 27-86%; p=0.015) and was inversely related to the level of basal hyper-insulinemia (R(2)=0.39; p=0.004). CONCLUSIONS: In cirrhosis GLUT4 protein content was quantitatively intact, while limiting glucose tolerance. This indicates loss of redundancy of the major glucose transport system, possibly related to the markedly decreased expression of its gene. Hyper-insulinemia may be a primary event. Our findings implicate the muscular GLUT4 system in the glucose intolerance of liver cirrhosis by a mechanism different from that in diabetes.

No effect of growth hormone administration on substrate oxidation during exercise in young, lean men.

The purpose of this study was to examine the effects of increased fat availability induced by growth hormone (GH) administration on the oxidative metabolism during exercise. Seven well-trained males (age 25 +/- 2 years (mean +/- S.E.M.); peak oxygen consumption : 62 +/- 1 ml min(-1) kg(-1) (completed four randomised trials: 120 min bicycling at 55% 4 h after receiving either 7.5 IU (2.5 mg) GH or placebo (Plc), and during rest after receiving either GH or Plc. In all studies a standardized meal was given 2 h after GH or Plc injection. GH administration resulted in an approximately 60-fold increase in serum GH concentration at rest (P < 0.0001) and during exercise (P < 0.0001). The increase in serum GH was followed by an increase in circulating glycerol at rest (8%, P < 0.0001). When combined with exercise the increase in plasma glycerol was more pronounced (GH: 716% of baseline versus Plc: 328%, P < 0.0001). However, this increase in fat mobilization did not increase fat oxidation during exercise (indirect calorimetry). In conclusion, GH administration combined with aerobic exercise increased lipolytic parameters substantially more than exercise alone, but did not further augment whole body fat oxidation.

Toward the development of a test for growth hormone (GH) abuse: a study of extreme physiological ranges of GH-dependent markers in 813 elite athletes in the postcompetition setting.

There is a need to develop a test to detect GH abuse by elite athletes. Measured levels of GH in blood or urine, however, provide little information on the GH-IGF-I axis. Previous studies have identified a series of indirect markers of GH action that are markedly altered by the administration of GH, but to a lesser degree by acute exercise. This study was undertaken to determine the physiological range of these GH-dependent variables in elite athletes after a competitive event to determine whether such values differ from resting values in normal and athletic subjects and to establish whether any adjustments to this range are required on the basis of age, gender, demographic characteristics, or the nature of the exercise performed. Serum samples were collected from 813 elite athletes (537 males and 276 females; age range, 17-64 yr) from 15 sporting disciplines within 2 h of completion of a major competitive event. IGF-I, IGF-binding protein 2 (IGFBP-2), IGFBP-3, acid-labile subunit, and the bone and soft tissue markers, osteocalcin, carboxyl-terminal propeptide of type I procollagen, carboxyl-terminal cross-linked telopeptide of type I collagen, and procollagen type III were measured. Sporting category, gender, age, height, weight, body mass index (BMI), and racial group of the athlete were documented, and results were compared both to normative data and to values obtained from elite athletes under resting conditions. Forty-one percent of IGF-I values in male athletes and 41% of values in female athletes were above the upper limits of 99% reference ranges derived from resting values in a normal population. Postcompetition levels of all variables except carboxyl-terminal propeptide of type I procollagen and carboxyl-terminal cross-linked telopeptide of type I collagen differed from resting values. There was a consistent age-dependent fall in measured levels of all variables (P < 0.0001) with the exception of IGFBP-2, which increased with age (P < 0.0001). BMI, but not height, exerted a small, but significant, influence on several variables. After adjustment for age, there were no significant differences in the levels of any of the measured variables between sporting categories. IGFBP-2 and IGFBP-3 were lower in 35 black athletes compared with those in 35 white athletes matched for age, gender, height, BMI, and sporting category. We have demonstrated that there are predictable age-dependent levels of GH-dependent markers in elite athletes that are consistent even at the extremes of physical exertion and that these are independent of sporting category. Normative data applicable to white athletes are provided. This provides important groundwork for the development of a test for GH abuse, although these values may be specific for the reagents and assays used.

Growth hormone increases vascular cell adhesion molecule 1 expression: in vivo and in vitro evidence.

We investigated the impact of GH administration on endothelial adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, in vivo and in vitro. Soluble VCAM-1, E-selectin, and C-reactive protein concentrations were measured before and after treatment in 25 healthy subjects and 25 adult GH-deficient (GHD) patients randomized to GH treatment or placebo. Furthermore, we studied the direct effect of GH and IGF-I and serum from GH-treated subjects on basal and TNF alpha-stimulated expression of VCAM-1 and E-selectin on cultured human umbilical vein endothelial cells. Baseline levels of VCAM-1, but not E-selectin, were significantly lower in GHD patients than in healthy subjects (362 +/- 15 microg/liter vs. 516 +/- 21 microg/liter, P < 0.001) and increased in GHD patients during GH treatment, compared with placebo [net difference between groups 151.8 microg/liter (95% confidence interval: 95.0-208.7 microg/liter); P < 0.0001]. In human umbilical vein endothelial cells, there was no direct stimulatory effect of either GH or IGF-I on the expression of VCAM-1 and E-selectin, but serum from GH-treated healthy subjects significantly increased the expression of VCAM-1 (P < 0.01). Our findings are compatible with the notion that GH may stimulate the expression of VCAM-1 indirectly through modulation of circulating factors. VCAM-1-mediated leukocyte extravasation is implicated in several illnesses including atherosclerosis and multiple-organ failure in sepsis, and we hypothesize that enhanced expression of VCAM-1 may contribute to the detrimental effects of GH in critically ill patients.

Acute exposure to GH during exercise stimulates the turnover of free fatty acids in GH-deficient men.

The secretion of growth hormone (GH) increases acutely during exercise, but whether this is associated with the concomitant alterations in substrate metabolism has not previously been studied. We examined the effects of acute GH administration on palmitate, glucose, and protein metabolism before, during, and after 45 min of moderate-intensity aerobic exercise in eight GH-deficient men (mean age = 40.8 +/- 2.9 yr) on two occasions, with (+GH; 0.4 IU GH) and without GH administered (-GH). A group of healthy controls (n = 8, mean age = 40.4 +/- 4.2 yr) were studied without GH. The GH replacement during exercise on the +GH study mimicked the endogenous GH profile seen in healthy controls. No significant difference in resting free fatty acid (FFA) flux was found between study days, but during exercise a greater FFA flux was found when GH was administered (211 +/- 26 vs. 168 +/- 28 micromol/min, P < 0.05) and remained elevated throughout recovery (P < 0.05). With GH administered, the exercise FFA flux was not significantly different from that observed in control subjects (188 +/- 14 micromol/min), but the recovery flux was greater on the +GH day than in the controls (169 +/- 17 vs. 119 +/- 11 micromol/min, respectively, P < 0.01). A significant time effect (P < 0.01) for glucose rate of appearance from rest to exercise and recovery occurred in the GH-deficient adults and the controls, whereas there were no differences in glucose rate of disappearance. No significant effect across time was found for protein muscle balance. In conclusion, 1) acute exposure to GH during exercise stimulates the FFA release and turnover in GH-deficient adults, 2) GH does not significantly impact glucose or protein metabolism during exercise, and 3) the exercise-induced secretion of GH plays a significant role in the regulation of fatty acid metabolism.

Acute growth hormone administration causes exaggerated increases in plasma lactate and glycerol during moderate to high intensity bicycling in trained young men.

We studied the acute effects of a single, sc GH dose on exercise performance and metabolism during bicycling. Seven highly trained men [age, 26 +/- 1 yr (mean +/- SEM); weight, 77 +/- 3 kg; maximal oxygen uptake, 65 +/- 1 ml O(2).min(-1).kg(-1)] performed 90 min of bicycling 4 h after receiving 7.5 IU (2.5 mg) GH or placebo in a randomized, double-blinded, cross-over design trial. A standardized pre-exercise meal was given 2 h before exercise. Blood was sampled at rest and during exercise and analyzed for GH, IGF-I, glucose, lactate, insulin, glycerol, and nonesterified fatty acids (NEFA). In the placebo trial, all subjects completed the exercise protocol without any difficulties. In contrast, two subjects were not able to complete the exercise protocol in the GH trial, and one subject barely managed to complete the protocol. In addition, GH administration resulted in exaggerated increases in plasma lactate concentrations during exercise (P < 0.0001). The combined lipolytic effect of GH and exercise, evidenced by increased plasma glycerol and serum NEFA concentrations, was 3-fold greater than the effect of exercise alone (P < 0.0001), but this increased substrate availability did not result in increased whole body fat oxidation (indirect calorimetry). Plasma glucose was, on average, 9% higher during exercise after GH administration compared with placebo (P < 0.0001). We conclude that a single, relevant GH dose causes exaggerated increases in plasma lactate and glycerol as well as serum NEFA during 90 min of subsequent bicycling at moderate to high intensity. The exaggerated increase in plasma lactate may be associated with substantially decreased exercise performance.

Preferential stimulation of abdominal subcutaneous lipolysis after prednisolone exposure in humans.

OBJECTIVE: The role of cortisol in the regulation of lipolysis is not clear. This study was undertaken to explore whether a standard dose of prednisolone for 1 week would influence lipolysis in abdominal and femoral tissue. RESEARCH METHODS AND PROCEDURES: We used the microdialysis technique, the forearm technique, and indirect calorimetry, in the fasting state, after 1 week of treatment with prednisolone (30 mg daily) or placebo. Eight healthy young men (age: 25 +/- 3 years; height: 181 +/- 1 cm; body mass index [BMI]: 23.3 +/- 0.7 kg/m(2)) were studied. RESULTS: Treatment with prednisolone induced insulin resistance (Homeostasis Model Assessment index: placebo vs. prednisolone: 7.15 +/- 1.63 vs. 17.00 +/- 14.26, p = 0.03), hyperinsulinemia (p = 0.01), and hyperglucagonemia (p = 0.001), whereas growth hormone concentrations were unaffected. Abdominal adipose tissue interstitial glycerol was increased during treatment with prednisolone in the face of significant hyperinsulinemia, although it barely reached statistical significance (p = 0.06). At the femoral adipose tissue depot, no difference in lipolysis was found. Arterial and venous free fatty acids (FFA) were comparable in the two situations, whereas the arteriovenous difference across the forearm was significantly decreased during treatment with prednisolone, indicating increased uptake, or decreased release of FFA. Energy expenditure (p = 0.3), respiratory quotient (p = 0.9), glucose oxidation (p = 0.9), lipid oxidation (p = 1.0), and protein oxidation (p = 0.1) were unaltered on the 2 study days. DISCUSSION: Short-term treatment with a standard dose of corticosteroids induces increased abdominal adipose tissue lipolysis, as well as hyperinsulinemia, hyperglucagonemia, and insulin resistance.

Plasma ghrelin levels during exercise in healthy subjects and in growth hormone-deficient patients.

OBJECTIVE: To characterise plasma levels of the recently identified endogenous ligand for the GH secretagogue receptor (ghrelin) during submaximal aerobic exercise in healthy adults and in GH-deficient adults. DESIGN: Eight healthy males (mean+/-s.e. age, 40.8+/-2.9 years) and eight hypopituitary males with verified GH deficiency (mean+/-s.e. age, 40.8+/-4.7 years) underwent a baseline test of their peak aerobic capacity (VO(2) peak) and lactate threshold (LT) on a cycle ergometer, as well as an evaluation of body composition. The patients were then studied on two occasions in random order when they exercised for 45 min at their LT. On one occasion, GH replacement had been discontinued from the evening before, whereas on the other occasion they received their evening GH in addition to an intravenous infusion of GH (0.4 IU) during exercise the following day. The healthy subjects exercised at their LT on one occasion without GH. RESULTS: The patients were significantly more obese and had lower VO(2) max (corrected for body weight) and LT as compared with the control subjects. Exercise induced a peak in serum GH concentrations after 45 min in the control group (11.43+/-3.61 microg/l). Infusion of GH in the patients resulted in a peak level after 45 min, whereas no increase was detected when exercising without GH (9.77+/-2.40 (GH) vs 0.11+/-0.07 microg/l (no GH)). Plasma ghrelin levels did not change significantly with time in either study, and no correlations were detected between ghrelin levels and parameters such as GH and IGF-I levels, age or body composition. Plasma ghrelin levels were significantly lower during the study period with GH as compared with the study with no GH. CONCLUSIONS: Submaximal aerobic exercise of an intensity sufficient to stimulate GH release was not associated with significant alterations in plasma ghrelin concentrations, which indicated that systemic ghrelin is not involved in the exercise-induced stimulation of GH secretion. The observation that ghrelin levels were lower during GH replacement suggests that GH may feedback-inhibit systemic ghrelin release.

Weight loss increases circulating levels of ghrelin in human obesity.

OBJECTIVE: Ghrelin, a novel endogenous ligand for the GH secretagogue receptor, has been reported to have adipogenic actions and induce weight gain in addition to its GH-releasing properties. Interestingly, recent data indicate that ghrelin is downregulated in human obesity, which is also known to be accompanied by reduced GH levels. PATIENTS AND METHODS: To investigate the influence of weight loss on circulating levels of ghrelin we recruited eight obese women among patients attending a 6-month weight-loss course organized by The Danish Heart Association. We measured body composition including computerized tomography as well as fasting plasma ghrelin concentrations before and after weight loss. RESULTS: Plasma ghrelin concentrations increased by 12% following weight loss (P < 0.01), and the increase in ghrelin levels was positively correlated with the extent of weight loss (r = 0.68, P < 0.05). Exposure to exogenous GH intravenously did not influence fasting ghrelin levels either before or after weight loss. Our data further suggest the existence of hyperghrelinaemia in a single subject with long-standing obesity but no signs of GH excess. CONCLUSIONS: This study provides evidence of a reversible suppression of ghrelin associated with obesity. The feasibility of measuring ghrelin in the circulation provides a new tool for the investigation of the complex hormonal regulation of appetite and energy balance.