Increase of serum lipoprotein (a) levels during growth hormone therapy in normal short children

We studied the effect of growth hormone (GH) therapy on serum lipoprotein levels and the atherogenic index in short children without GH deficiency. Fasting blood samples were collected from ten (eight males) normal, short, prepubertal children, aged 6–12 years, before, during a 1-year course of GH therapy (0.1 IU/Kg/day), and 3 months after the cessation of GH administration. An increase in serum lipoprotein(a) [Lp(a)] levels of (mean% ± SEM) 43 ± 14, 58 ± 18, 61 ± 17 above the baseline levels was noted at 3 months (P<0.05), 6 months (P<0.01), and 1-year (P<0.01) respectively after the beginning of GH administration. (ANOVA, P<0.01). An inverse relationship between baseline serum Lp(a) concentrations and the percentage increment in Lp(a) after 9 months of GH therapy (r=−0.65,P<0.05) was observed. GH therapy over a period of 1 year had no effect on plasma cholesterol, triglycerides, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein cholesterol [HDL-C] concentrations and the atherogenic index. Three months after the cessation of GH therapy, serum Lp(a) levels were not significantly different from the pre-treatment values. Conclusions Serum Lp(a) concentrations remained above pretreatment values during a 1-year period of GH treatment in short children without GH deficiency and declined shortly after cessation of therapy. Since GH therapy for short children without GH deficiency usually continues for several years, we suggest that serum Lp(a) levels should be determined and followed regularly in such children under prolonged GH therapy. Received: 11 February 1997 and in revised form: 10 June 1997 / Accepted: 6 July 1997     

Cardiovascular risk factors improve during 3 years of growth hormone therapy in Prader-Willi syndrome

Cardiovascular risk factors in Prader-Willi syndrome (PWS, OMIM 176270) may be independently caused by overweight or hypothalamic growth hormone (GH) deficiency. The present observational study in 23 children with PWS, aged 0.3–14.6 years, focuses on the specific pattern, age-dependency and interrelation of cardiovascular risk factors, namely percentage fat mass and regional fat distribution, triglycerides (TG), lipoprotein cholesterols (LDL-C, HDL-C), lipoprotein (a) (Lp(a)), apolipoproteins A-I (Apo A-I) and B (Apo B), as well as on the longer-term effects of GH therapy (ca. 0.037 mg/kg per day for 3 years on average). We report that in children above 4 years, percentage body fat was increased in all and waist-to-hip-ratio (WHR) in 35%. Abnormal levels of LDL-C, Apo B, HDL-C and TG were found in 6, 7, 6 and 3 children, respectively. Lp(a) was above 300 mg/l in 5 patients and remained unchanged during GH therapy. However, percentage fat mass dropped to the upper normal range and WHR became normal in all patients receiving GH therapy, as did the ratio of LDL-C to HDL-C, subsequent to decreasing LDL-C and increasing HDL-C. Nevertheless, we could not find any significant correlation between parameters of total fat mass or fat distribution and serum lipid parameters, except for abdominal fat distribution (trunk-/leg-fat ratio) to TG before therapy. Conclusion Several cardiovascular risk factors are already present in prepubertal children with Prader-Willi-syndrome and they are improved by growth hormone treatment, acting both on body composition and lipid metabolism. Received: 25 January 2000 / Accepted: 9 May 2000     

Use of permissive hypercapnia in the ventilation of infants with respiratory syncytial virus infection

We wished to retrospectively evaluate the effects of permissive hypercapnia (PHY) on barotrauma, mortality and length of stay when applied to ventilated infants with respiratory syncytial virus (RSV) bronchiolitis. Nineteen control infants with RSV induced respiratory failure were treated with conventional ventilation (April 1991–January 1994), after which time PHY was adopted as unit policy. A further 28 infants were then treated with PHY (January 1994–April 1996). Demographic and physiological data were collected from admission, and outcome variables including length of stay, barotrauma and mortality were recorded. The PHY group showed a significantly higher mean pCO₂ (7.6 vs 5.2 kPa), a lower mean pH (7.34 vs 7.40), and a reduction in maximal peak inspiratory pressures (25 vs 30 cmH₂O). Mortality, barotrauma, use of neuromuscular blockade and nosocomial infection did not differ between groups. There was a trend towards increased length of ventilation in the PHY group (median 7 vs 5 days). Conclusion Based on this retrospective data we can show no benefit for the use of permissive hypercapnia as a ventilatory strategy in this patient group. A prospective randomised controlled trial is warranted to accurately assess the outcome variables and cost implications of this strategy. Received: 22 June 1998 / Accepted in revised form: 25 August 1998     

Low insulin, IGF-I and IGFBP-3 levels in children with Prader-Labhart-Willi syndrome

It is well established that insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and insulin are low in growth hormone deficiency, but due to their dependence on nutrition, they are elevated in healthy obese children. As the presence of growth hormone deficiency in Prader-Labhart-Willi syndrome (PWS) is still controversial, we studied insulin, IGF-I and IGFBP-3 levels in 19 children with PWS (age range 0.5–14.6 years). Serum concentrations of insulin (SDS: −0.7±0.9, P=0.01) and IGF-I (SDS: −0.7±0.8,P=0.002) were low, but IGFBP-3 (SDS: −0.3±1.2, P=0.2) was normal compared to normal weight age-matched children. Since children with PWS are typically obese, insulin, IGF-I and IGFBP-3 levels should be compared to normal obese children who present increased levels of these hormones. In comparison to data of healthy obese children reported in the literature, not only IGF-I, but also IGFBP-3 levels are low and fasting insulin levels even very low, suggesting a growth hormone deficiency. Received: 19 November 1997 / Accepted in revised form: 2 March 1998     

Effect of growth hormone therapy on bone metabolism of growth hormone deficient children

The effects of human growth hormone (hGH) therapy on biochemical markers of bone metabolism were studied in 17 children (10 boys and 7girls, aged 3.7–13.1 years old) with idiopathic GH deficiency, before and 1 and 6 months after GH therapy (0.5–0.7 IU/kg weekly, SC). Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, parathyroid hormone, 1,25 dihydroxyvitamin D, insulin-like growth factor I (IGF-I) and renal phosphate per 100 ml glomerular filtrate (TPO₄/GFR) were assessed. During therapy with hGH, a significant decrease of serum calcium levels and increases of phosphate, osteocalcin, parathyroid hormone 1,25 dihydroxyvitamin D and IGF-I were observed. TPO₄/GFR was also significantly increased. Growth response (increment in HV) was positively related with changes in alkaline phosphatase and IGF-I levels after 6 months of hGH therapy. There was also a significant positive correlation between increment in HV and increment in TPO₄/GFR after 1 month of GH therapy, whereas no correlation between HV and changes in osteocalcin levels was found. Conclusion GH treatment significantly influences mineral metabolism and the measurement of TPO₄/GFR after 1 month of GH therapy may serve as a useful predictor of growth response to hGH therapy in GH-deficient children. Received: 16 August 1996 / Accepted: 5 February 1997     

Abnormal ventilatory responses in patients with Prader-Willi syndrome

Abnormal ventilatory control in patients with Prader-Willi syndrome when awake and sleeping include abnormal responses to hyperoxia, hypoxia and hypercarbia. Lindgren et al., report similar results regarding response to hypoxia; however, they have demonstrated significant minute ventilation and carbon dioxide responses in their patients treated with growth hormone irrespective of body mass index. It is possible that the explanation for the abnormal respiratory control in this syndrome is located in central rather than peripheral structures. The hypothalamus stands out as the possible location that links their abnormal ventilatory control with the other features. Further investigations to correlate this finding are warranted. Received: 20 April 1999 / Accepted: 21 April 1999     

The influence of growth hormone monotherapy and growth hormone in combination with oxandrolone or testosterone on thyroxid hormone parameters and thyrxine binding globulin in patients with Ullrich- Turner syndrome

 Administration of human growth hormone (GH) has yielded conflicting results concerning its role on thyroid function in patients with Ullrich-Turner syndrome. Therefore, we investigated the course of thyroid hormone parameters and thyroxin binding globulin in relation to GH therapy, IGF-I and additional oxandrolone-(Ox) or testosterone (T) treatment in 20 patients with Ullrich-Turner syndrome. During the 1st year the patients received only GH. There was no change in T4, fT4, and TSH levels, T3 increased significantly (P <  0.01) after 6 and 12 months, resulting in a higher T3/T4 ratio. TBG (P < 0.05) and IGF-I (P < 0.01) increased after 6 months and remained elevated at 12 months. A significant positive correlation was found between the change of T4 and TBG after 6 months (r = 0.47, P < 0.05) and after 12 months (r = 0.69, P < 0.005). Thirteen patients were further investigated after addition of an anabolic compound; 7 received Ox (0.0625 mg/kg/day po) and 6 low dose T (5 mg i.m. every 14 days). Chronological age was comparable in these groups (10.7 ±  2.7 vs 10.7  ± 3.6 years). After 6 months of combination therapy with Ox, T4, T3 and TSH decreased. As T4 and T3 showed a parallel decrease the T3/T4 ratio remained elevated. TBG declined after 6 and 12 months (P < 0.05), while IGF-I showed a further increment (P < 0.05). There was no correlation between the changes in T4 and IGF-I, TSH and TBG, respectively. In the T-treated group only IGF-I increased (P < 0.05) to the same extent as in the Ox-treated patients, whereas the thyroid parameters did not change. Conclusion The observed changes in thyroid hormone and TBG levels in the Ox group were not mediated by GH or IGF-I. The Ox-induced TBG decrease might be linked to altered pancreatic functions regulating carbo-hydrate metabolism. Received: 22 April 1996 / Accepted: 1 August 1996     

Growth hormone secretion, puberty and adult height after cranial irradiation with 18 Gy for leukaemia

The dose of prophylactic cranial irradiation given to patients for acute lymphoblastic leukaemia has been decreased from 24 to 18 Gy, but the beneficial effect of this decrease on growth is controversial. This study compares the growth hormone (GH) secretion and growth of 35 patients (20 boys) given 18 Gy at 3.7 ± 0.3 (SE) years, and routinely evaluated 5.4 ± 0.4 years after irradiation to define the indications for GH treatment in these patients. Of these, 63% had a low GH peak (<10 μg/l) after one (22 cases) or two (17 cases) stimulation tests. The plasma concentrations of insulin-like growth factor I and its GH-dependent binding protein were normal for age in all but two cases. The height changes between irradiation and evaluation were correlated with the GH peaks (P < 0.03) and were concordant, except in patients with early puberty. This occurred in 16 patients including all 12 girls irradiated before 4 years of age. A significant (P < 0.03) reduction in height (SD) between irradiation and adult height occurred in untreated GH-deficient patients (−1 ± 0.3, n = 6), but not in GH-deficient patients given GH (−0.6 ± 0.3, n = 8) or in those with normal GH peak (−0.4 ± 0.3, n = 7). Conclusion In children irradiated for acute lymphoblastic leukaemia, GH deficiency is frequent after 18 Gy but its impact on adult height is smaller than after higher doses. We suggest that the indications for gonadotropin releasing hormone analogue therapy should be broad in patients with early or rapidly progressing puberty and those for GH therapy in those patients with a below average constitutional height before irradiation. Received: 17 November 1997 / Accepted: 9 February 1998     

Magnetic resonance images of 91 children with different causes of short stature: pituitary size reflects growth hormone secretion

In order to validate an association between pituitary size and severity of growth hormone deficiency (GHD) we evaluated the magnetic resonance images (MRI) of 107 children with different causes of short stature. Ninety-one MRIs were evaluable (64 male, 27 female; age: 9.1 ± 3.9 years). The levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), and tests of GH stimulation and spontaneous secretion, led to the following sub-groups: severe isolated GHD (SIGHD) (GH < 7 ng/ml) (n = 21); partial, isolated GHD (GH 7–10 ng/ml) (n = 22); multiple pituitary hormone deficiency (MPHD) (n = 13); neurosecretory dysfunction (n = 10); non-classifiable diagnosis (NC) (n = 13); idiopathic short stature (n = 9); and intra-uterine growth retardation (n = 3). Pituitary height (PHT) was measured and hypoplasia was assumed when PHT was <−2 SDS. An ectopic posterior pituitary with missing stalk and a hypoplastic anterior pituitary was present in 12 (57%) SIGHD cases, 12 (92%) MPHD cases and 1 patient from the NC group. An isolated hypoplastic anterior pituitary was observed in 15%−33% of the other groups. PHT (mm; mean, SD) in MPHD (1.7 ± 0.5) was lower than in SIGHD (2.7 ± 1.0, P < 0.05), with PHT of both groups being lower than in all the other groups (3.8 ± 0.9, P < 0.0001). PHT SDS correlates with IGF-I SDS (r = 0.48, P < 0.0001), IGFBP-3 SDS (r = 0.46, P < 0.0001) and the highest peaks in tests of GH stimulation and GH spontaneous secretion (r = 0.36, P < 0.0001). In contrast to all the other groups, no correlation with age was observed in MPHD and SIGHD. Breech delivery was recorded in up to 26% of patients in all seven groups. Surprisingly, only 1 out of 23 patients with an ectopic posterior pituitary was born by breech delivery, suggesting that ectopia of the posterior lobe is not necessarily related to breech delivery. Conclusion PHT is significantly correlated with GH secretion in several types of short stature. Patients with␣ectopic posterior pituitary, missing stalk and hypoplastic␣anterior pituitary either suffer from SIGHD or MPHD, and this anatomical defect is not necessarily related to breech delivery. Received: 1 December 1996 and in revised form: 8 February 1997 / Accepted: 18 February 1997     

Appropriate positive end expiratory pressure level in surfactant-treated preterm infants

Positive end expiratory pressure (PEEP) is routinely used when ventilating preterm infants, and high levels are recommended in those with severe respiratory distress syndrome (RDS). Elevation of PEEP increases lung volume, as does surfactant administration. We postulated that in surfactant-treated infants even modest PEEP levels could result in overdistension and (CO₂) retention. To test that hypothesis, lung volume, compliance and arterial blood gases were measured in eight preterm infants (median gestational age 28 weeks, range 26–35 weeks) at three PEEP levels. The infants, all with RDS, were studied at a median time of 18 h, (range 12–68 h) after their last dose of surfactant. Infants were routinely nursed at 3 cmH₂O of PEEP, the PEEP level was then raised to 6 cmH₂O or lowered to 0 cmH₂O in random order. The new setting was maintained for 20 min; the PEEP level was then changed to the third level (0 or 6 cmH₂O) again for 20 min. At the end of each 20-min period, lung volume, compliance and blood gases were measured. Lung volume was assessed by measuring functional residual capacity (FRC) using a helium dilution technique. Compliance was measured by relating the volume change from a positive pressure inflation maintained until no further volume change occurred to the pressure drop (peak inflating pressure PEEP). Increasing PEEP from 0 to 3 cmH₂O and particularly to 6 cmH₂O resulted in increases in FRC (P < 0.05), oxygenation (ns) and paCO₂ (P < 0.02). Specific compliance (compliance/FRC) (P < 0.05) and pH (P < 0.02) fell. Conclusion Following surfactant treatment, relatively low levels of positive end expiratory pressure (≤3 cmH₂O) may be appropriate. Received: 20 April 1999 / Accepted: 26 May 1999     

The effects of synthetic and natural surfactant on fluid balance in acute respiratory distress syndrome

To evaluate the effect of different surfactants on fluid balance in respiratory distress syndrome, we studied 24 premature infants who were randomised to receive either natural or synthetic surfactant. Data were collected on ventilatory parameters, daily urine output, daily weight, fluid intake and serum electrolytes. Ventilatory requirements decreased more rapidly in babies receiving natural surfactant, with significantly greater reductions in mean airway pressure from 1 to 48 h and oxygenation index from 1–18 h (P < 0.05). There were no differences in fluid intake and serum electrolytes. Mean daily urine output was higher in the group receiving natural surfactant (87 ml versus 61 ml, P < 0.05). This group also had a greater weight loss from birth weight (−146 g versus −65 g, P < 0.05). Conclusion Natural surfactant produces an earlier reduction in ventilatory requirements with an earlier diuresis. This should influence fluid management in respiratory distress syndrome. Received: 10 February 2000 / Accepted: 24 April 2000     

Managing respiratory problems in Prader–Willi syndrome

Children with Prader Willi syndrome (PWS) are at risk of developing both central and obstructive sleep apnoea in the context of dysfunctional respiratory control, a small upper airway and obesity. Growth hormone (GH) promotes body composition, psychosocial development and quality of life. Despite evidence of its stimulatory effect on the ventilatory drive, GH has been associated with unexpected nocturnal deaths in high risk patient groups such as the obese and those with pre existing respiratory problems. Using a case study, the present article explores issues around respiratory investigations, the safe use of GH and non invasive ventilation in children with PWS.     

Growth, puberty and hypothalamic-pituitary function in children with suprasellar arachnoid cyst

A suprasellar arachnoid cyst may cause disorders of growth, puberty and hypothalamic-pituitary function, due to the proximity of the cyst to the hypothalamic-pituitary area. A total of 30 patients (17 boys) with cyst diagnosed at 4.3 ± 1 years were routinely evaluated at 5.4 ± 1 years; 24 of them had one or multiple cyst derivations. Some 23 cases had an abnormal height, weight or puberty: short (<−2SD, 5 cases) or tall (>2SD, 10 cases) stature, overweight (body mass index, BMI, >2SD, 6 cases), central precocious puberty (10 cases) and/or no progression of pubertal development (3 cases). The growth hormone (GH) peaks after pharmacological stimulation test were low (<10 μg/l) in 16 patients, confirmed by a second evaluation in 8/11 of them. The plasma free thyroxine was low in five patients, prolactin was high in two and the cortisol and concomitant plasma and urinary osmolalities were normal. BMI was correlated negatively with the GH peaks (r=−0.37, P < 0.01) and positively with the plasma leptin concentrations (r=0.55, P < 0.01). The plasma fasting insulin concentrations were also correlated negatively with the GH peaks (r=−0.55, P < 0.02) and positively with the plasma insulin-like growth factor I concentrations (r=0.64, P < 0.002). The adult height (12 cases) was at 4SD in 1 and <−2SD in 4 patients, two of whom had precocious puberty untreated with gonadotropin releasing hormone (GnRH) analogue, and two had untreated GH deficiency. The adult height of those treated was normal. One girl had primary amenorrhoea and two boys had low plasma testosterone, despite a normal gonadotropin response to a GnRH test. Conclusion Suprasellar arachnoid cysts may cause deficiencies of growth hormone and thyrotropin, stimulation of the hypothalamic-pituitary-gonadal axis, tall stature and/or overweight. These last two disorders may be due to hyperinsulinism, itself due to suprasellar arachnoid cyst. Received: 5 May 1999 / Accepted: 28 October 1999     

Mannose-binding lectin polymorphisms and recurrent respiratory tract infection in Chinese children

In order to establish the reference value of mannose-binding lectin (MBL) serum level in children and to investigate the correlation between the polymorphisms of MBL2 gene and serum MBL level in healthy Chinese of Han ethnic group and in children of Chinese Han ethnic group with recurrent respiratory tract infections (RRTI), the concentration of oligomerized MBL was measured by enzyme-linked immunosorbent assay, and MBL2 gene polymorphisms were analyzed by restriction fragment length polymorphism of polymerase chain reaction and polymerase chain reaction-sequence specific primer. The median MBL levels in the 470 normal children were 2536 ng/ml, and the P_2.5–P_97.5 was 161–5,070 ng/ml. Our research showed that two promoter polymorphisms at −550, −221 of start codon and coding variants at codon 54 of MBL2 gene affected the protein level significantly and the most frequent genotype in Hans is HYPA/HYPA. Our results also showed that serum MBL level was significantly lower in recurrent respiratory tract infections patients compared with healthy controls (Z, −3.04, P = 0.002). The frequency of the promoter LXP haplotype and the B allele was significantly higher in RRTI patients than in controls (χ ² 4.05, P < 0.05; OR 1.63, 95%CI 1.01∼2.62; χ ² 4.27, P < 0.05; OR 1.94, 95%CI 1.02∼3.68). Conclusion: We have established that the reference value of serum MBL level in Chinese aged between 0 and 6 years (161–5,070 ng/ml), and we found that LXP and the B are risk factors for RRTI.     

The effect of growth hormone on sleep-related cardio-respiratory control in Prader-Willi syndrome

Aim: To evaluate the effects of growth hormone (GH) treatment on control of breathing, heart rate and blood pressure during sleep in Prader–Willi Syndrome (PWS). Study design: in a prospective clinical case series study, sixteen consecutive PWS patients (median age 16 months at enrolment) were followed‐up 6 months (2–32 months) after commencing GH treatment. We compared heart rate (HR), Pulse Transit Time (PTT; an index of blood pressure, BP) and ventilatory responses to standard chemostimuli (4% CO₂ and 100% O₂) during quiet sleep prior to and after commencing GH treatment. Results: Growth hormone treatment increased arterial oxygenation during sleep but did not significantly improve breathing stability (apnoea‐hypopnoea index remained unchanged). GH treatment did not alter ventilatory, HR and PTT chemoreceptor‐mediated responsiveness (p = 0.23–0.97) but did significantly improve the coupling between and HR and PTT, indicating that HR and BP rose (or fell) in parallel after but not before GH therapy (p = 0.01). Conclusion: Growth hormone treatment improves arterial oxygenation and cardiovascular function during sleep; these changes are not owing to improved (stronger) chemoreflex‐mediated autonomic drive.     

Sustained benefit after 2 years of growth hormone on body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome

BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition resembling a growth hormone (GH)-deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. Although recent studies have demonstrated short-term benefits of treatment with GH, a critical question is whether beneficial changes persist or wane with prolonged therapy. OBJECTIVES AND METHODS: Effects of 24 months of GH treatment (1 mg/m(2)/d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure, and fat utilization were assessed in 35 children with PWS. Percent body fat, lean muscle mass, and bone mineral density were measured by dual-energy x-ray absorptiometry. Indirect calorimetry was used to determine resting energy expenditure and to calculate the respiratory quotient. RESULTS: Compared with baseline evaluations, increased height velocity (SD score -1.1 +/- 2.5 to 2.2 +/- 2.3; P <. 001), reduced percent body fat (46.4% +/- 8.4% to 40.3% +/- 10.0%, P <.001), and improved respiratory muscle function and physical strength and agility (sit-ups, weight-lifts, running speed, and broad jump; P <.01) were observed after 24 months of GH treatment. A decline in respiratory quotient (0.81 +/- 0.07 to 0.75 +/- 0.06; P <. 01) and a trend toward increased resting energy expenditure were also observed. Changes in response to GH occurred predominantly during the initial 12 months of GH therapy. CONCLUSIONS: Children with PWS had sustained increases in lean body mass, decreases in percent body fat, improvements in physical strength and agility, and increased fat oxidation after 24 months of GH therapy. However, between 12 and 24 months, the growth rate slowed. Consequently, encouraging initial results require even more prolonged study to draw conclusions regarding the long-term value of GH therapy in changing body composition in children with PWS.     

Precision of continuous neonatal ventilator respiratory mechanics is improved with selected optimal respiratory cycles

Given their high apparent variability, bedside continuous respiratory mechanics (RM) parameters [excepting tidal volume (V _T)] remain infrequently used for adjustment of neonatal ventilatory settings. RM parameters provided by ventilator (VRC) from ten recordings of newborns [10 min in synchronised intermittent mandatory ventilation and 10 min in assist/control (A/C)] were compared to those computed from visually selected assisted leak-free optimal respiratory cycles (SRC). Mean values, variability and ability to distinguish patients were compared between VRC and SRC. Dynamic resistances were more correlated (r ² = 0.95) than compliances (r ² = 0.42). V _Ts were correlated only in A/C (r ² = 0.78). C20/C was significantly higher in VRC (1.81 ± 0.67) than in SRC (1.23 ± 0.36) and frequently out of neonatal reference range. In A/C ventilation, V _T was higher in VRC (5.6 ± 1.8 ml/kg) than in SRC (4.8 ± 1.0 ml/kg) (p < 0.05). Displayed V _Ts do not reflect those found in optimal assisted breaths and therefore have incomplete value in assessing adequacy of ventilator settings. The variability of RM parameters provided by the ventilator is large, and coefficients of variation were significantly lower with optimal respiratory cycles (for resistance, compliance, V _T and C20/C; 27%, 26%, 18%, 24% in SRC and 36%, 35%, 40% and 33% in VRC). Selecting optimal cycles yields RM with two to three times higher discriminating power between patients. Conclusion: Current ventilator’s RM parameters have limited clinical use. Using optimal breaths to calculate RM parameters improves precision and discriminating power. For integration to ventilatory care, automation of this selection must be implemented first.     

Growth hormone treatment enhances bone mineralisation in children with chronic renal failure

Dual energy X-ray absorptiometry of the whole body and the lumbar spine was performed to study bone mineralisation before and after 1 year of recombinant human growth hormone (rhGH) treatment in ten children with chronic renal failure. At the start, median age was 7.3 years (range 2.0–8.8 years) and median glomerular filtration rate 15 ml/min per 1.73 m² (range 7–41 ml/min per 1.73 m²). Total body mineral content (TBMC), lumbar spine mineral content (LBMC), total body bone mineral density (TBMD) and lumbar spine mineral density (LBMD) improved significantly (P < 0.05) after 1 year of treatment. Bone mineral data before and after treatment were compared with two groups of controls, i.e. ten healthy children matched for age and ten healthy children matched for height. Patients' TBMC, LBMC, TBMD and LBMD data before treatment were no different from those of height-matched controls; the same was true after 1 year of treatment except for the patients' significantly better LBMD (P < 0.05). When compared with age-matched controls, patients had significantly lower baseline TBMC and LBMC levels before treatment; after treatment LBMC was no longer different. However, there were no differences in TBMD or LBMD between patients and age-matched controls at baseline or after rhGH. Conclusion Recombinant human growth hormone treatment for 1 year results in a significant increase in both growth velocity and bone mineralisation. Comparison with height-matched controls shows a similar bone mineralisation at baseline and a better bone mineral density after treatment. Received: 10 August 2000 and in revised form 10 November 2000 and 5 January 2001 /  Accepted: 8 January 2001     

Disease-related response to inhaled nitric oxide in newborns with severe hypoxaemic respiratory failure

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10–80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51 ± 21 vs 23 ± 17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45 ± 20 vs 20 ± 17, P < .0001), `idiopathic' PPHN (39 ± 14 vs 14 ± 9, P < .0001), and sepsis (55 ± 25 vs 26 ± 20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI = 41 ± 16 vs 28 ± 18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI = 58 ± 25 vs 46 ± 32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age ≥34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants. Received: 24 April 1997 / Accepted in revised form 3 January 1998     

In vitro release of eosinophil cationic protein from peripheral eosinophils reflects disease activity in childhood Crohn disease and ulcerative colitis

The aim of this study was to compare in vitro release of eosinophil cationic protein (ECP) from peripheral blood eosinophils during active phases of childhood Crohn disease (CD) and ulcerative colitis with phases of remission. Ten children with CD and nine children with ulcerative colitis were investigated during 55 and 56 clinical visits, respectively. Each patient was investigated during at least one phase of clinically active disease and one phase of remission. Disease activity was assessed by means of the Paediatric Crohn Disease Activity Index (PCDAI) in Crohn disease and according to the clinical activity index of Rachmilewitz in ulcerative colitis. On an intra-individual basis, in vitro ECP release was significantly higher (P < 0.001) during active phases of CD and ulcerative colitis than in phases of remission (CD:median: 24.5 μg/l, range 16.0–61.2 versus median: 5.7 μg/l, range 2.0–16.7; ulcerative colitis: 14.8 μg/l, 8.3–39.8 versus 4.9 μg/l, 2.0–9.9). On an inter-individual basis, in CD and ulcerative colitis a strong and highly significant correlation was observed between disease activity indices and in vitro release of ECP from peripheral eosinophils (r = 0.89, P < 0.0001 and r = 0.82, P < 0.0001, respectively). Conclusion These results show that in vitro ECP release from peripheral eosinophils reflects disease activity in both CD and ulcerative colitis and therefore can be used as a new appropriate laboratory parameter for assessment of disease activity in chronic inflammatory bowel disease. Received: 26 October 1996 and in revised form: 8 April 1997 / Accepted: 15 April 1997