T. Stijnen

J-shaped relation between change in diastolic blood pressure and progression of aortic atherosclerosis

The J-shaped relation between diastolic blood pressure and mortality from coronary heart disease continues to provoke controversy. We examined the association between diastolic blood pressure and progression of aortic atherosclerosis in a population-based cohort of 855 women, aged 45-64 years at baseline. The women were examined radiographically for calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. After 9 years of follow-up, slight progression of atherosclerosis was noted in 19% of women and substantial progression in 16%. The age-adjusted relative risk of substantial atherosclerotic progression in women with a decrease in diastolic pressure of 10 mm Hg or more was 2.5 (95% CI 1.3-5.6), compared with the reference group of women who had a smaller decrease or no change. The excess risk in this group was confined to women whose increase in pulse pressure was above the median (3.9 [1.5-9.9] vs 1.1 [0.3-4.2] in women with an increase in pulse pressure below the median). The relative risks for women with rises in diastolic pressure of 1-9 mm Hg and 10 mm Hg or more were 2.2 (1.1-4.3) and 3.5 (1.6-8.0), respectively. These findings suggest that a decline in diastolic blood pressure indicates vessel wall stiffening associated with atherosclerotic progression. They support the hypothesis that in low-risk subjects progression of atherosclerosis may be accompanied by a decrease in diastolic blood pressure rather than the opposing idea that low diastolic blood pressure precipitates the occurrence of atherosclerotic events.

Endogenous and stimulated GH secretion, urinary GH excretion, and plasma IGF‐I and IGF‐II levels in prepubertal children with short stature after intrauterine growth retardation

OBJECTIVE The pathophysiological mechanisms underlying the failure of catch up‐growth in children with short stature after Intrauterine growth retardation (IUGR) remain obscure. Since GH secretion disturbances might play a role in the growth retardation of these children we have Investigated various aspects of the GH/IGF axis.

Cigarette smoking and the development and progression of aortic atherosclerosis. A 9-year population-based follow-up study in women.

BackgroundCigarette smoking has been recognized as an important risk factor for cardiovascular disease in men and women. Whether the increased risk results from an atherogenic effect of smoking is still debated. We examined the relation between cigarette smoking and atherosclerotic changes in the abdominal aorta. Methods and ResultsThe association between cigarette smoking and atherosclerotic changes in the abdominal aorta was examined in a population-based cohort of 758 women, initially aged 45 to 64 years. All women were examined radiographically for calcified deposits in the abdominal aorta, which have been shown to represent intimal atherosclerosis. After 9 years of follow-up, atherosclerotic changes, indicating development or progression of plaques, could be demonstrated in 37% of women. A direct association was found between atherosclerotic change and number of cigarettes smoked per day. Compared with women who had never smoked, the relative risks of those who smoked 1 to 9, 10 to 19, and 20 or more cigarettes per day were 1.4 (95% confidence interval, 1.0 to 2.0), 2.0 (1.6 to 2.5), and 2.3 (1.8 to 3.0), respectively, after adjustment for age and other cardiovascular risk factors. Associations of atherosclerotic change with inhaling habit and duration of smoking were borderline significant after number of cigarettes smoked per day was taken into account. Among former smokers, the risk decreased with increasing duration of stopping but a significant excess risk was still observed after 5 to 10 years since quitting (relative risk, 1.6; 95% confidence interval, 1.1 to 2.2). ConclusionsThese follow-up data support the evidence for an effect of cigarette smoking on atherosclerosis. The findings suggest that the rate of atherosclerotic change may be reduced by cessation of smoking, but a residual effect appears to be present for at least 10 years.

Final Height and Its Predictive Factors after Renal Transplantation in Childhood

ABSTRACT: A retrospective study is reported assessing final height (FH) and its predictive factors in 52 patients (31 male, 21 female) who underwent renal transplantation (RTx) before the age of 15 y. They received prednisone daily or on alternate days as well as azathioprine. The study period covered 20 y. FH remained below the third height percentile [height standard deviation score for chronologic age (hSDSCA) < −1.88] for most of these patients (77% males, 71% females). Median (range) FH was 165.0 (143.0–176.8) cm in males and 153.0 (135.0–168.4) cm in females. Median difference between FH and target height was 15.0 and 15.4 cm for males and females, respectively. For both sexes, the median hSDSCA was already below −1.88 at the start of the first hemodialysis, after which it decreased significantly until the first RTx. After RTx, there was no significant improvement of hSDSCA. The predictive factors for FH were determined by evaluating various factors simultaneously in a multiple regression analysis. This analysis provided a regression equation for predicting FH. A higher hSDSCA at the time of the first RTx and alternate-day versus daily prednisone therapy both had a significantly positive influence on FH, whereas a longer duration of reduced GFR (<50 mL/min/1.73 m2) had a significantly negative effect on FH. Other factors such as age or bone age at first RTx, primary renal disease, duration of initial dialysis, repeat RTx, and the cumulative dose of prednisone did not influence FH significantly. In conclusion, 71–77% of patients that received their first renal transplant before the age of 15 ended up with severely short adult stature. Optimization of the hSDSCA at first RTx appears very important. Long-term administration of prednisone on alternate days would then result in optimal FH, particularly if the GFR remains above 50 mL/min/1.73 m2.

Long-Term Effects of Treatment for Acute Lymphoblastic Leukemia with and without Cranial Irradiation on Growth and Puberty: A Comparative Study

ABSTRACT: We investigated the comparative effect on long-term growth of CNS prophylactic treatment for acute lymphoblastic leukemia (ALL) with either 25-Gy cranial irradiation or moderate-dose i.v. methotrexate. In 80 children with complete continuous first remission, data on growth and pubertal development were investigated up to 11 y from ALL diagnosis. Forty patients had 25-Gy cranial irradiation, 16 of them with high-risk factors and 24 without. Another 40 non-high-risk ALL patients had moderate-dose methotrexate. Chemotherapy lasted 31/4 y for high-risk ALL patients and 21/4 y for those not at high risk. Pubertal development and final height were assessed separately for girls diagnosed before or after age 7 and for boys before or after age 9. All patients had a similar decline in height SD score during the first 6 mo of treatment, which persisted in irradiated children only. The nonirra-diated group had no further decline. Catch-up growth only started when chemotherapy ended for irradiated and non-irradiated patients alike. Five y after cessation of treatment, changes in height SD score for nonirradiated children remained within the range for healthy children against a significant decline in height SD scores for irradiated children. Pubertal development in irradiated girls diagnosed before age 7 was within normal range, but their final height was disappointing due to a blunted growth spurt. In contrast, irradiated girls diagnosed later had a delayed onset of puberty but satisfactory final height. Comparable results were found in boys. In summary, 25-Gy cranial irradiation in the treatment of ALL causes long-term growth retardation, whereas moderate-dose i.v. methotrexate seems to have only a temporary effect on growth.

Apolipoprotein E genotype and progression of Alzheimer’s disease: the Rotterdam Study

Abstract The APOE*4 allele of the apolipoprotein E gene increases the risk of Alzheimer’s disease (AD), but whether it also affects the course of the disease is controversial. However, all studies on this issue until now have been based on patients at various stages of disease. In the present population-based study, 97 patients were included at a similar stage, i.e., before the onset of symptoms, and followed for up to 5 years. We found that the APOE*4 allele is not a strong determinant of survival in AD. As change in cognitive function and severity of dementia are similar for AD patients with and without APOE*4, our study suggests that progression of AD is not related to the APOE*4 allele.

Standards for total body fat and fat-free mass in infants.

Data on body composition in conjunction with reference centiles are helpful in identifying the severity of growth and nutritional disorders in infancy and for evaluating the adequacy of treatment given during this important period of rapid growth. Total body fat (TBF) and fat-free mass (FFM) were estimated from total body electrical conductivity (TBEC) measurements in 423 healthy term Caucasian infants, aged 14-379 days. Cross sectional age, weight, and length related centile standards are presented for TBF and FFM. Centiles were calculated using Altmans method, based on polynomial regression and modelling of the residual variation. The TBF percentage steeply increased during the first half year of life, and slowly declined beyond this age. Various simple TBEC derived anthropometric prediction equations for TBF and FFM are available to be used in conjunction with these standards. Regression equations for the P50 and the residual SD, depending on age, weight, or length, are provided for constructing centile charts and calculating standard deviation scores.

Conventional and controlled release valproate in children with epilepsy: a cross-over study comparing plasma levels and cognitive performances

We studied plasma levels and behavioural effects of a newly developed controlled release formulation of valproate (VPA-CR) in children with epilepsy. Valproate plasma levels and performances in attention and vigilance tasks were monitored during a 12-h period (daytime), both during monotherapy of conventional valproate (VPA) and 4 weeks after switching to a similar dosage of VPA-CR taken once daily. There was no significant difference between the two formulations with respect to mean diurnal trough and peak valproate plasma levels, and to mean fluctuation. The significantly higher Cmax/Cmin ratio during VPA-CR seems mainly due to low valproate plasma levels early in the morning. Neuropsychological assessment showed no significant differences, either between patients and controls, or within patients and controls when comparing the results obtained on the VPA and VPA-CR day. During both VPA and VPA-CR treatment, no correlation was found between cognitive performance and valproate plasma levels. The advantage of VPA-CR is that the once daily regimen may increase compliance and is more convenient for schoolchildren.

Effect of growth hormone administration frequency on 24‐hour growth hormone profiles and levels of other growth related parameters in girls with Turner's syndrome

OBJECTIVE The optimal dose and frequency of GH administration in Turners syndrome is unknown. There is some evidence that a schedule which mimics normal pulsatile GH secretion may be more effective than a single dally dose. We therefore wished to study the influence of the frequency of GH administration on 24‐hour GH profiles and levels of other growth‐related factors in Turners syndrome.

A regression method including chronological and bone age for predicting final height in Turner's syndrome, with a comparison of existing methods

A total of 235 measurement points of 57 Dutch women with Turners syndrome (TS), including women with spontaneous menarche and oestrogen treatment, served to develop a new Turner‐specific final height (FH) prediction method (PTS). Analogous to the Tanner and Whitehouse mark 2 method (TW) for normal children, smoothed regression coefficients are tabulated for PTS for height (H), chronological age (CA) and bone age (BA), both TW RUS and Greulich and Pyle (GP). Comparison between all methods on 40 measurement points of 21 Danish TS women showed small mean prediction errors (predicted minus observed FH) and corresponding standard deviation (ESD) of both PTSRUS and PTSGP, in particular at the “younger” ages. Comparison between existing methods on the Dutch data indicated a tendency to overpredict FH. Before the CA of 9 years the mean prediction errors of the Bayley and Pinneau and TW methods were markedly higher compared with the other methods. Overall, the simplest methods—projected height (PAH) and its modification (mPAH)—were remarkably good at most ages. Although the validity of PTSRUS and PTSGP remains to be tested below the age of 6 years, both gave small mean prediction errors and a high accuracy. FH prediction in TS is important in the consideration of growth‐promoting therapy or in the evaluation of its effects.