A novel mutation in ABCD1 unveils different clinical phenotypes in a family with adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. The disease is the consequence of mutations in the ABCD1 gene that encodes the peroxisomal membrane protein ALDP which is involved in the transmembrane transport of very long-chain fatty acids. We describe a family with six members carrying a novel heterozygous mutation IVS4+2T>A (c.1393+2T>A) of the ABCD1 gene, highlighting the wide range of phenotypic manifestations of ALD and the importance of genetic screening before any pregnancy in asymptomatic women whose carrier status is unknown.

[Prognosis and treatment of Vernal keratoconjunctivitis in pediatric age: pilot study on 197 patients]. / Prognosi e trattamento della cheratocongiuntivite Vernal in età pediatricia: studio pilota su 197 pazienti.

AIM: Corticosteroids and high-concentrated cyclosporine eyedrops have been used for treatment of severe vernal keratoconjunctivitis (VKC) cases. The purpose of our study was to verify the efficacy of 1% topical cyclosporine in improving severe form of VKC in childhood and investigate for factors affecting the response to therapy. METHODS: We conducted an open trial involving 197 children with severe VKC, who received topical cyclosporine 1% for four months. Ocular subjective symptoms and objective signs were scored in all children at entry, two weeks and four months. Skin prick tests and microscope endothelial cells evaluation were also performed; serum IgE and cyclosporine levels were assessed. RESULTS: The mean score values for severity of subjective symptoms and objective signs were significantly decreased after 2 weeks, and 4 months, compared with those at entry (P<0.001) in all children. Cyclosporine serum levels were not detectable at the end of therapy, nor were endothelial corneal cells damaged. Patients who started the therapy at the beginning of the disease and/or received long-term regimen of treatment with cyclosporine had a faster improvement of ocular signs and symptoms, compared to all other patients. CONCLUSION: Our findings suggest that 1% cyclosporine concentration administrated topically at the beginning of the disease and for a long-term period might be the most effective treatment to control symptoms and local inflammation in severe forms of VKC in childhood.

Faster top running speeds are achieved with greater ground forces not more rapid leg movements.

We twice tested the hypothesis that top running speeds are determined by the amount of force applied to the ground rather than how rapidly limbs are repositioned in the air. First, we compared the mechanics of 33 subjects of different sprinting abilities running at their top speeds on a level treadmill. Second, we compared the mechanics of declined (-6 degrees ) and inclined (+9 degrees ) top-speed treadmill running in five subjects. For both tests, we used a treadmill-mounted force plate to measure the time between stance periods of the same foot (swing time, t(sw)) and the force applied to the running surface at top speed. To obtain the force relevant for speed, the force applied normal to the ground was divided by the weight of the body (W(b)) and averaged over the period of foot-ground contact (F(avge)/W(b)). The top speeds of the 33 subjects who completed the level treadmill protocol spanned a 1.8-fold range from 6.2 to 11.1 m/s. Among these subjects, the regression of F(avge)/W(b) on top speed indicated that this force was 1.26 times greater for a runner with a top speed of 11.1 vs. 6.2 m/s. In contrast, the time taken to swing the limb into position for the next step (t(sw)) did not vary (P = 0.18). Declined and inclined top speeds differed by 1.4-fold (9.96+/-0.3 vs. 7.10+/-0.3 m/s, respectively), with the faster declined top speeds being achieved with mass-specific support forces that were 1.3 times greater (2.30+/- 0.06 vs. 1.76+/-0.04 F(avge)/ W(b)) and minimum t(sw) that were similar (+8%). We conclude that human runners reach faster top speeds not by repositioning their limbs more rapidly in the air, but by applying greater support forces to the ground.

Establishing a standard definition for child overweight and obesity worldwide: international survey.

OBJECTIVE: To develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, the reference population, and the age and sex specific cut off points. DESIGN: International survey of six large nationally representative cross sectional growth studies. SETTING: Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the United States. SUBJECTS: 97 876 males and 94 851 females from birth to 25 years of age. MAIN OUTCOME MEASURE: Body mass index (weight/height(2)). RESULTS: For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut off points of 25 and 30 kg/m(2) for adult overweight and obesity. The resulting curves were averaged to provide age and sex specific cut off points from 2-18 years. CONCLUSIONS: The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.

PIP: This study aimed to develop an internationally acceptable definition of child overweight and obesity, specifying the measurement, reference population, and age and sex specific cut off points. Data on body mass index (weight/height) were obtained from 6 large nationally representative cross sectional surveys on growth from Brazil, Great Britain, Hong Kong, the Netherlands, Singapore, and the US. The study included 97,876 males and 94,851 females from birth to 25 years of age. For each of the surveys, centile curves were drawn that at age 18 years passed through the widely used cut-off points of 25 and 30 kg/sq. m for adult weight and obesity. The resulting curves were averaged to provide age- and sex-specific cut-off points from 2 to 18 years. The proposed cut off points, which are less arbitrary and more internationally based than current alternatives, should help to provide internationally comparable prevalence rates of overweight and obesity in children.

Workshop on childhood obesity: summary of the discussion.

Childhood obesity is rapidly emerging as a global epidemic that will have profound public health consequences as overweight children become overweight adults. To address this problem, action is needed at national and international levels. However, well-documented evidence of the trends in and global prevalence of obesity in children and adolescents is required to develop sound public health policies. There is no internationally acceptable index to assess childhood obesity nor is there an established cutoff point to define overweight in children. The purpose of the workshop was to establish a reasonable index with which to assess adiposity (overweight) in children and adolescents worldwide. We present here a summary of the discussion on the establishment of an index. The participants concluded that although body mass index (BMI; in kg/m2) is not a perfect measure in children because it covaries with height, it has been validated against measurements of body density. Because a consistent and pragmatic definition for overweight in children and adolescents is required, BMI may therefore be appropriate. However, other alternatives may be considered in the future. The group suggested a scheme for cutoff points for children and adolescents based on internationally accepted BMI cutoff points for adult morbidity of 25 and 30 to identify grade 1 and grade 2 overweight, respectively. Use of these cutoff points would provide a new approach to identifying childhood obesity and make the definition for children and adolescents consistent with that for adults.

Introduction: the use of body mass index to assess obesity in children.

The International Obesity Task Force (IOTF) was established in 1994 to address the increase in the worldwide prevalence of obesity. The goals of the IOTF are to 1) raise awareness in the population and among governments that obesity is a serious medical condition, 2) develop policy recommendations for a coherent and effective global approach to the management and prevention of obesity, and 3) implement appropriate strategies to manage and prevent obesity on a population basis worldwide. To assess the global prevalence of obesity in children and adolescents, the IOTF convened a workshop on childhood obesity to determine the most appropriate measurement to assess obesity in populations of and adolescents around the world. At the workshop, a variety of issues related to this problem were considered--including the best measure of fatness, the effect of application of a variety of existing standards on the prevalence of obesity in the same population, and the role of factors such as visceral adiposity and natural history in the definition of obesity. This article and those that follow represent the information presented at the workshop. The workshop concluded that the body mass index (BMI; in kg/m2) offered a reasonable measure with which to assess fatness in children and adolescents and that the standards used to identify overweight and obesity in children and adolescents should agree with the standards used to identify grade 1 and grade 2 overweight (BMI of 25 and 30, respectively) in adults.

High-speed running performance is largely unaffected by hypoxic reductions in aerobic power.

We tested the importance of aerobic metabolism to human running speed directly by altering inspired oxygen concentrations and comparing the maximal speeds attained at different rates of oxygen uptake. Under both normoxic (20.93% O2) and hypoxic (13.00% O2) conditions, four fit adult men completed 15 all-out sprints lasting from 15 to 180 s as well as progressive, discontinuous treadmill tests to determine maximal oxygen uptake and the metabolic cost of steady-state running. Maximal aerobic power was lower by 30% (1.00 +/- 0.15 vs. 0.77 +/- 0.12 ml O2. kg-1. s-1) and sprinting rates of oxygen uptake by 12-25% under hypoxic vs. normoxic conditions while the metabolic cost of submaximal running was the same. Despite reductions in the aerobic energy available for sprinting under hypoxic conditions, our subjects were able to run just as fast for sprints of up to 60 s and nearly as fast for sprints of up to 120 s. This was possible because rates of anaerobic energy release, estimated from oxygen deficits, increased by as much as 18%, and thus compensated for the reductions in aerobic power. We conclude that maximal metabolic power outputs during sprinting are not limited by rates of anaerobic metabolism and that human speed is largely independent of aerobic power during all-out runs of 60 s or less.

Effects of antioxidants on vascular health.

Substantial in vitro and animal model evidence implicates the free radical-mediated oxidation of low density lipoprotein and its subsequent preferential uptake by macrophages in the arterial intima as an important factor in the development of vascular disease. In addition, antioxidants which prevent the oxidation of LDL in vitro also reduce the severity of vascular disease in animal models. Although some epidemiological studies also suggest that inadequate antioxidant status is related to the development of vascular disease, particularly cardiovascular disease, results from intervention trials have been contradictory. Whereas vitamin E may have a role in reducing the incidence of vascular disease, evidence is less strong for vitamin C, flavonoids and beta-carotene. Additionally, supplementation with some antioxidants such as beta-carotene may increase the incidence of cancer in high risk groups. Although increasing antioxidant intake is generally beneficial for health, this should perhaps be achieved by an increased dietary intake of antioxidant-rich foods rather than by use of supplements.

Does the application of ground force set the energetic cost of cross-country skiing?

We tested whether the rate at which force is applied to the ground sets metabolic rates during classical-style roller skiing in four ways: 1) by increasing speed (from 2.5 to 4.5 m/s) during skiing with arms only, 2) by increasing speed (from 2.5 to 4.5 m/s) during skiing with legs only, 3) by changing stride rate (from 25 to 75 strides/min) at each of three speeds (3.0, 3.5, and 4.0 m/s) during skiing with legs only, and 4) by skiing with arms and legs together at three speeds (2.0-3.2 m/s, 1.5 degrees incline). We determined net metabolic rates from rates of O2 consumption (gross O2 consumption - standing O2 consumption) and rates of force application from the inverse period of pole-ground contact [1/tp(arms)] for the arms and the inverse period of propulsion [1/tp(legs)] for the legs. During arm-and-leg skiing at different speeds, metabolic rates changed in direct proportion to rates of force application, while the net ground force to counteract friction and gravity (F) was constant. Consequently, metabolic rates were described by a simple equation (metab = F . 1/tp . C, where metab is metabolic rates) with cost coefficients (C) of 8.2 and 0.16 J/N for arms and legs, respectively. Metabolic rates predicted from net ground forces and rates of force application during combined arm-and-leg skiing agreed with measured metabolic rates within +/-3. 5%. We conclude that rates of ground force application to support the weight of the body and overcome friction set the energetic cost of skiing and that the rate at which muscles expend metabolic energy during weight-bearing locomotion depends on the time course of their activation.

Oxidative DNA damage measured in human lymphocytes: large differences between sexes and between countries, and correlations with heart disease mortality rates.

The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids, and other antioxidants occurring in fruit and vegetables afford protection against heart disease and cancer by preventing oxidative damage to lipids and to DNA, respectively. To test elements of this hypothesis, we have measured blood levels of dietary antioxidants, and 8-oxodeoxyguanosine (8-oxo-dG) concentrations in lymphocyte DNA, in healthy men and women from five European countries: France, Ireland, The Netherlands, Spain, and the U.K. Volunteers, aged 25 45, all nonsmokers, gave blood samples before and after a 12-wk carotenoid supplementation regime. Vitamin C was measured in plasma and vitamin E and carotenoids were measured in serum by high-performance liquid chromatography (HPLC). 8-oxo-dG was assayed by HPLC (with coulometric detection) in DNA isolated from lymphocytes from the same blood samples. Mean values were calculated for groups of volunteers at each sampling time according to country, sex, and supplementation (between 9 and 24 individual samples contributing to each mean). We found that 8-oxo-dG levels in lymphocyte DNA vary significantly according to sex and country. A low mean 8-oxo-dG concentration is seen in DNA of women from all five countries, and of men from France and Spain. 8-oxo-dG is significantly higher (up to about threefold) in lymphocyte DNA from men in Ireland and the U.K. Oxidative DNA damage is not significantly affected by carotenoid supplementation; nor is there any association with mean baseline levels of antioxidants, which are generally similar in the five countries. The five countries sampled lie on an axis from northern to southern Europe with a steep gradient in terms of premature heart disease. There is a strong association between premature coronary heart disease mortality in men and the mean levels of 8-oxo-dG for the five countries (r = 0.95, P < 0.01). Women have low coronary heart disease mortality rates, which do not correlate with 8-oxo-dG. In terms of cancer deaths, only colorectal cancer in men shows a significant positive correlation (r = 0.91, P < 0.05), and stomach cancer in women is negatively correlated with DNA oxidation (r = -0.92, P = 0.01).

alpha-Tocopherol binding activity of red blood cells in smokers.

Despite high plasma levels of vitamin E, red blood cell membranes contain relatively low levels of vitamin E. This suggests the existence of a selective vitamin E uptake/regeneration system in human red blood cell membranes. alpha-Tocopherol binding sites on human red blood cells are thought to be involved in the uptake of alpha-tocopherol from the plasma. To understand the role of the uptake system we have compared the alpha-tocopherol content and binding activity of red blood cells from smokers and non-smokers. The specific binding of [3H] alpha-tocopherol to pure red blood cell preparations from smokers (n = 7, 28.4 +/- 2.8 years) was 30.6 +/- 3.2 fmoles per 3 x 10(8) red blood cells and for non-smokers (n = 17, 27.9 +/- 1.3 years) was 41.7 +/- 3.7 fmoles per 3 x 10(8) red blood cells. Thus alpha-tocopherol uptake activity was significantly lower in smokers (P = 0.05). Red blood cells from smokers contained less (1.8 +/- 0.4 micrograms/gHb) alpha-tocopherol than non-smokers (2.8 +/- 0.3 micrograms/gHb), (P < 0.05), despite plasma levels of alpha-tocopherol being similar: 12.9 +/- 0.8 microM in non-smokers vs. 12.7 +/- 0.5 microM in smokers. However, adjusting plasma alpha-tocopherol for total plasma cholesterol plus triacylglycerols showed alpha-tocopherol levels were higher (P < 0.01) in non-smokers (2.84 +/- 0.10 mumol alpha-tocopherol/ mmol [cholesterol+triacylglycerol]) than in smokers (2.36 +/- 0.11 mumol alpha-tocopherol/mmol [cholesterol+triacylglycerol]). The reduced alpha-tocopherol levels in red blood cells from smokers may be due to impairment of alpha-tocopherol uptake activity. The reduced levels of alpha-tocopherol in smokers red blood cells was not associated with any changes in cell membrane fluidity. At present it is not known whether supplementation of smokers with vitamin E would normalise the alpha-tocopherol uptake activity of red blood cells.

High D-glucose does not affect binding of alpha-tocopherol to human erythrocytes.

The role of alpha-tocopherol uptake system in human erythrocyte in the uptake of plasma alpha-tocopherol has been suggested. However no information is available on alpha-tocopherol uptake activity of human erythrocytes in the presence of high levels of D-glucose which is known to lead to pathological alterations in different cells including human erythrocytes. Therefore, in order to examine the effect of D-glucose on the binding of alpha-tocopherol to human erythrocytes, the binding characteristics of alpha-tocopherol to these cells were established first. Binding of [3H]alpha-tocopherol to human erythrocytes was both saturable and specific. Scatchard analysis of alpha-tocopherol binding to these cells showed the presence of two independent classes of binding sites with widely different affinities. The high affinity binding sites had a dissociation constant (Kd1) of 90 nM with a binding capacity (n1) of 900 sites per cell, whereas the low affinity binding sites had a dissociation constant (Kd2) of 5.2 microM and a binding capacity (n2) of 105,400 sites per cell. Trypsin treatment abolished all the alpha-tocopherol binding activity. Competition for the binding of alpha-tocopherol to human erythrocytes was effective with other homologues of alpha-tocopherol (beta-tocopherol, gamma-tocopherol and delta-tocopherol) and their potency was almost equal to alpha-tocopherol itself. The order of preference was alpha-tocopherol > beta-tocopherol > or = gamma-tocopherol > or = delta-tocopherol. Incubation of human erythrocytes with various concentrations of D-glucose did not affect alpha-tocopherol uptake activity. Our data demonstrate the presence of an alpha-tocopherol uptake system in human erythrocytes and that the alpha-tocopherol uptake activity is not modulated by the presence of D-glucose.

Vitamin E and coronary heart disease: the European paradox.

OBJECTIVE: To relate premature mortality from coronary heart disease (CHD) to national food and nutrient supplies. DESIGN: Descriptive correlational study. SETTING: Nineteen western European and five non-European countries. METHODS: Premature mortality from CHD in men below 65 years was related to recalculated Food and Agriculture Organization (FAO) food, antioxidant vitamins and other nutrient supply data in 24 developed countries for 1985-87. Longitudinal analyses of death rates from CHD and supplies between 1970 and 1987 were carried out for all the countries. Correlational analyses of supplies that preceded mortality by up to 10 years were also undertaken. RESULTS: In 17 western European countries the inter-country association of dairy product supply with CHD was of moderate strength (r = 0.5) and the principal saturated fatty acids derived from dairy products: butyric, caproic and myristic acids (C4:0, C6:0 and C14:0) were the most strongly related with CHD (r = 0.5, 0.5 and 0.4 respectively). The phenolic-antioxidant-rich foods, e.g. wine, vegetables and vegetable oils, were inversely related to CHD (r = -0.8, -0.7 and -0.6 respectively). Of the antioxidant vitamins, the alpha-tocopherol component of vitamin E was strongly related to CHD across Europe (r = -0.8). The major determinant of alpha-tocopherol supply was usually sunflowerseed oil. Vitamin C and beta-carotene gave moderate correlations (r = -0.6 and -0.5 respectively). Latency periods of 5 and 10 years between supplies and mortality rates did not markedly change the correlations. Longitudinal analyses of nutrient supplies and death rates within each country from 1970 to 1987 also showed that for the majority of countries there was an inverse association between supply of alpha-tocopherol and CHD. CONCLUSIONS: Dietary alpha-tocopherol may provide at least as good an explanation as does wine for the paradoxically low rates of CHD in several European countries which have a relatively high saturated fatty acid intake.

[Short-term comparison of the treatment of precocious puberty with 2 different LHRH antagonists (buserelin and long-acting triptorelin). An endocrinologic and echographic study]. / Confronto a breve termine del trattamento della pubertà precoce con due diversi antagonisti dell'LHRH (Buserelin e Triptorelina a cessione protratta). Studio endocrinologico ed ecografico.

To compare the short term effects of a short (Buserelin, 1800 micrograms/day as nasal spray) and a long acting (Triptorelin Depot, 3.75 mg/every 4 weeks i.m.) LHRH agonist, LH and FSH (LHRH test and 2 hours spontaneous rhythm during the morning and during the evening), estradiol and pelvic ultrasonography were evaluated in 12 children (1 boy, mean age 8.24 +/- 1.39 years, mean bone age 9.39 +/- 1.76 years) with early puberty before and after 1 and 2 months of treatment. Informed consent was obtained in all the cases. 6 patients started with Buserelin and 6 with Triptorelin. The therapeutic regimen was crossed over after 2 months of treatment and 2 more months of treatment withdrawal. The results indicate that while in both groups FSH values decreased significantly already from the last month of treatment, patients treated with Triptorelin showed a later LH decrease (significant only after 2 months of treatment). A decrease of pelvic structures volume was however evident only in patients treated with Triptorelin. After 2 months of treatment estradiol levels lowered (but not significantly) in both group. In conclusion despite a later LH decrement, patients treated with the long acting analogue showed however a more evident reduction of pelvic organs volume.

Nutrition policy development and implementation in Malta.

The paper highlights experiences in the development and implementation of the food and nutrition policy in Malta. As one could expect there has been tangible progress in certain areas but less so in others. Some background information on the food and health status of the Maltese population is given first as this was the reason for the establishment of the policy in Malta in the first place.