Low birth weight due to intrauterine growth restriction is associated with various diseases in adulthood, such as hypertension, cardiovascular disease, insulin resistance and end-stage renal disease. ...The purpose of this review is to describe the effects of intrauterine growth restriction on the kidney. Nephrogenesis requires a fine balance of many factors that can be disturbed by intrauterine growth restriction, leading to a low nephron endowment. The compensatory hyperfiltration in the remaining nephrons results in glomerular and systemic hypertension. Hyperfiltration is attributed to several factors, including the renin-angiotensin system (RAS), insulin-like growth factor (IGF-I) and nitric oxide. Data from human and animal studies are presented, and suggest a faltering IGF-I and an inhibited RAS in intrauterine growth restriction. Hyperfiltration makes the kidney more vulnerable during additional kidney disease, and is associated with glomerular damage and kidney failure in the long run. Animal studies have provided a possible therapy with blockage of the RAS at an early stage in order to prevent the compensatory glomerular hyperfiltration, but this is far from being applicable to humans. Research is needed to further unravel the effect of intrauterine growth restriction on the kidney.
Metabolic bone disease and growth retardation are common complications of chronic renal failure (CRF). We evaluated bone mineral density (BMD), bone metabolism, body composition and growth in ...children with CRF, and the effect of growth hormone treatment (GHRx) on these variables. Thirty-three prepubertal patients with CRF were enrolled including 18 children with growth retardation, who were treated with growth hormone for 2 years. Every 6 months, BMD of lumbar spine and total body, and body composition were measured by dual-energy X-ray absorptiometry. Biochemical parameters of bone turnover were assessed. Mean BMD of children with CRF did not differ from normal. During GHRx, BMD and bone mineral apparent density of lumbar spine and height SDS increased, whereas BMD of total body did not change. Lean body mass increased in the GH group. Alkaline phosphatase increased significantly in the GH group only. The other biochemical parameters of bone turnover increased in both groups, none of them correlated with the changes in BMD. No serious adverse effects of GHRx were reported. In conclusion, BMD of children with CRF did not differ from healthy children. Adequate treatment with alpha-calcidiol or the short duration of renal failure may have attributed to the absence of osteopenia in our patients. BMD of the axial skeleton and growth improved with GHRx.
OBJECTIVE
Osteopenia has been reported in adult patients with chronic renal failure (CRF). Only a few studies have been performed in children. The objective of this study was to evaluate bone mineral ...density (BMD), bone turnover, body composition in children with CRF and to study the effect of GH on these variables.
DESIGN
Two groups were identified: patients with growth retardation who received GH (GH‐group) and patients most of whom were not growth retarded who did not receive GH (no‐GH‐group). After an observation period of 6 months, the patients in the GH‐group started GH treatment. Patients were studied every 6 months during 18 months.
PATIENTS
Thirty‐six prepubertal patients (27 boys and 9 girls), mean age 7.9 years, with CRF participated in the study. The GH‐group consisted of 17 patients of whom 14 completed one year treatment. The no‐GH‐group consisted of 19 patients, of whom 16 were followed for 6 months, 14 for 12 months and 13 for 18 months.
MEASUREMENTS
Lumbar spine BMD, total body BMD and body composition were assessed by dual energy X‐ray absorptiometry, compared to age‐and sex‐matched reference values of the same population and expressed as standard deviation scores (SDS). BMD of appendicular bone was measured by quantitative microdensitometry (QMD). Blood samples were obtained to assess bone metabolism and growth factors.
RESULTS
Baseline mean lumbar spine and total body BMD SDS of all patients were not significantly different from normal. Mean lumbar spine and total body BMD SDS did not change significantly in the GH‐group during GH treatment. The change of QMD at the midshaft during the first 6 months of GH treatment was significantly smaller than during the observation period (P < 0.01). Height SDS and biochemical markers of both bone formation and bone resorption increased significantly during GH treatment; 1,25‐dihydroxyvitamin D remained stable. Lean tissue mass increased (P < 0.001) and percentage body fat decreased (P < 0.01) during GH treatment. BMD, the biochemical markers of bone turnover which are independent of renal function, and body composition remained stable in the no‐GH‐group.
CONCLUSIONS
Mean lumbar spine and total body BMD of children with chronic renal failure did not differ from healthy controls. The lack of a GH‐induced increase in 1,25‐dihydroxyvitamin D levels, probably due to treatment with alpha‐calcidol, might be linked to the absence of a response in BMD during GH treatment in children with chronic renal failure.
This article examines whether the involvement of stakeholders in the design of corporate codes of conduct leads to a higher implementation likelihood of the code. The empirical focus is on ...Occupational Safety and Health (OSH). The article compares the inclusion of OSH issues in the codes of conduct of 30 companies involved in International Framework Agreements (IFAs), agreed upon by trade unions and multinational enterprises, with those of a benchmark sample of 38 leading Multinational Enterprises in comparable industries. It is found that codes of the IFA group have a higher implementation likelihood in OSH than the codes of the benchmark group. Further, European firms, culturally more used to stakeholder involvement, score higher than their US and Japanese competitors, and hence are more capable of addressing the safety and health issues in international supply chains. The implementation likelihood of codes seems closely related to the type of corporate CSR approach.
The hemodynamic and pharmacokinetic effects of the novel class 1c antiarrhythmic drug restacorin were investigated in two groups of patients. Group I consisted of 5 patients with normal left ...ventricular (LV) function, and group II consisted of 10 patients with mild heart failure New York Heart Association (NYHA) II; mean LV ejection fraction 33 +/- 6%. The study had an open label, baseline-controlled, single-dose design. Restacorin was infused in a total dosage of 1.2 mg/kg. In group I, the only significant change as compared with baseline findings was a 25% increase in right atrial pressure. In group II; cardiac output (CO), dP/dt, and stroke work index (SWI) decreased significantly (-18, -11, and -24%, respectively). In addition, a significant 32% increase was noted in pulmonary artery wedge pressure (PAWP), and a 27% increase occurred in systemic vascular resistance (SVR). No changes were observed in heart rate (HR) or mean arterial blood pressure (MAP). CO and SVR at baseline correlated with the average plasma concentrations (r = -0.65 and p = 0.009 and r = 0.56 and p = 0.028 respectively). Creatinine clearance was inversely correlated to the restacorin plasma concentration (r = -0.51, p = 0.05). The half-life (t1/2) elimination time of restacorin was 2.60 h for group I, and 4.06 h for group II. Clearance was 51.4 and 32.2 L.h-1, respectively. Restacorin appears to be well tolerated in patients with normal LV function. The drug is not recommended for use in patients with reduced LV function because of its moderate negative inotropic effect.
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