Adenylosuccinate lyase deficiency in the United Kingdom pediatric population: first three cases.

Adenylosuccinate lyase deficiency is an autosomal recessive disorder of purine metabolism resulting from mutations in the ADSL gene on chromosome subband 22q13.1 and associated with a wide range of clinical manifestations. Although there is currently no effective treatment of ADSL deficiency, recognition of the condition is important, because prenatal genetic diagnosis can be offered to affected families. Reported here are the cases of the only three children diagnosed to date in the United Kingdom with adenylosuccinate lyase deficiency, to further delineate the clinical phenotype and to raise awareness of this disorder.

Extracranial internal carotid arterial disease in children with sickle cell anemia.

BACKGROUND: Sickle cell anemia is one of the commonest causes of stroke in children. It is usually, but not always, associated with intracranial vasculopathy. We have assessed the value of ultrasound screening for extracranial internal carotid artery disease. DESIGN AND METHODS: Using Doppler ultrasound scanning, we assessed peak systolic blood velocity, tortuosity and stenosis in the extracranial internal carotid arteries of 236 children with sickle cell anemia. Seventeen of the children had previously had a stroke. All measurements were performed as part of routine clinical care. RESULTS: The median extracranial internal carotid artery velocity was 148cm/s (5(th) centile 84, 95(th) centile 236). Higher velocities were significantly correlated with younger age, higher white blood cell counts and higher rates of hemolysis. Fourteen (5.9%) had tortuous extracranial internal carotid arteries and 13 (5.4%) had stenosis or occlusion. None of the children with tortuous vessels but 8 of those with stenosis had previously had a stroke; the presence of stenosis was strongly associated with overt clinical stroke (OR 35.9, 95% C.I. 9.77-132, P<0.001). In 6 children, extracranial stenosis was part of extensive intracranial vasculopathy, but in 2 there was no evidence of intracranial disease. Stenosis seemed to be more common in older children. CONCLUSIONS: Extracranial internal carotid artery stenosis is strongly associated with stroke in children with sickle cell anemia, and may explain some cases of stroke without overt intracranial vasculopathy. Doppler ultrasound scanning of extracranial internal carotid arteries is non-invasive and fairly quick to perform and may identify children at increased risk of stroke who would otherwise be missed. The value of extracranial internal carotid artery scanning should be studied prospectively.

A simple index using age, hemoglobin, and aspartate transaminase predicts increased intracerebral blood velocity as measured by transcranial Doppler scanning in children with sickle cell anemia.

OBJECTIVE: Increased intracerebral blood velocity measured by transcranial Doppler scanning identifies children with sickle cell anemia who are at increased risk of stroke. We have tried to develop an index based on routine clinical measurements that also predicts increased intracerebral blood flow. METHOD: Routinely collected clinical and laboratory data were correlated with transcranial Doppler measurements on children with sickle cell anemia seen in a single institution in 2006. The index produced was validated on a second independent data set from children with sickle cell anemia. RESULTS: The time-averaged mean of the maximum velocity in centimeters per second in the middle cerebral artery circulation correlated significantly with age, hemoglobin, lactate dehydrogenase, and aspartate transaminase levels, white blood cell count, and creatinine level. On multiple regression, hemoglobin and aspartate transaminase levels maintained their significance, whereas age had borderline significance, and an index was developed linked to a time-averaged mean of the maximum velocity of 220 - (8 x hemoglobin) - (1.4 x age) + (0.4 x aspartate transaminase). This detected a time-averaged mean of the maximum velocity of >170 cm/second with 100% sensitivity and 58% specificity. The index was validated on the second data set and again showed 100% sensitivity with 73% specificity. CONCLUSION: This simple index has the potential to identify children who are at higher risk of cerebrovascular disease to allow them to be prioritized for transcranial Doppler scanning and other intracerebral imaging.

Transcranial Doppler scanning and the assessment of stroke risk in children with HbSC [corrected] disease.

OBJECTIVE: To assess the role of transcranial Doppler (TCD) scanning in assessing the risk of stroke in children with haemoglobin SC (HbSC) disease. TCD scanning has an established role in primary stroke prevention in sickle cell anaemia but its value in HbSC is unknown. DESIGN: A retrospective audit of routinely performed TCD scans and routinely collected clinical data. SETTING: A paediatric sickle cell clinic in a teaching hospital in south London, UK. PATIENTS: 46 children with HbSC disease who have undergone routinely performed TCD scans and steady-state blood tests. MAIN OUTCOME MEASURES: The time-averaged mean of the maximum velocity (TAMMV) in the middle cerebral artery circulation correlated with clinical and laboratory data. RESULTS: The mean TAMMV was 94 cm/s, with a 98(th) centile of 128 cm/s. This is significantly less than the published ranges for HbSS, with a mean reading of 129 cm/s. One child had a stroke at the age of 5 years, when her TAMMV was measured at 146 cm/s. CONCLUSIONS: Further studies are needed to assess stroke risk in HbSC disease, but we suggest that TCD measurements are potentially useful in this condition, and that readings greater than 128 cm/s are abnormally high and warrant further investigation.

Hyperthermia increases exercise-induced oxidative stress.

The purpose of this investigation was to examine oxidative markers after exercise in a hyperthermic environment (35 degrees C, 70 % RH) (Hot) versus a neutral environment (25 degrees C, 40 % RH) (Con). Hyperthermia may exacerbate oxidative stress by uncoupling the mitochondrial respiratory chain or by inhibiting antioxidant defense mechanisms, but this has not been assessed in vivo. Six male subjects performed low-intensity exercise (50 % VO(2max)) on a treadmill in Hot until a core temperature of 39.5 degrees C was reached, and for an equivalent time in Con. Blood samples were drawn before and immediately after exercise and at 8 min and 15 min following exercise. Samples were analyzed for F2 isoprostanes (FIP), lipid hydroperoxides (LPO), and lactate. A 2 x 4 repeated measures ANOVA was used to test for treatment, time, and interaction effects for FIP, LPO, and lactate. Differences in VO(2) were tested with Student's t-test. Significance was set at p < 0.05. Oxygen consumption was not significantly different between Hot and Con. The pattern of change of FIP and lactate in Hot was significant versus exercise in Con. LPO was significantly elevated over time in both Hot and Con, but the pattern of change was not significantly different. Ending core temperatures and heart rates were significantly elevated in Hot versus Con. These data indicate that hyperthermia increases oxidative stress and selectively affects specific lipid markers, independent of oxygen consumption.

Nutritional status and lipid profiles of trained steroid-using bodybuilders.

Fourteen trained male anabolic steroid-using bodybuilders (SBBs) (19-41 years) were recruited for the study. Three-day diet records were obtained from SBBs and analyzed. A resting venous blood sample was drawn, and serum/plasma was subsequently analyzed for various nutritionally related factors. Results showed that mean dietary energy (4,469 +/- 1,406 kcal), protein 252 +/- 109 g), and vitamin and mineral intakes of SBBs greatly exceeded U.S. Recommended Dietary Allowances. Dietary cholesterol intake was 2.8 times the recommended levels. Mean serum/plasma nutrient concentrations of SBBs were within normal range. However, individual SBBs had a number of serum/plasma values outside of the normal or recommended range, the most notable of which was hypercalcemia, which was present in 42% of SBBs. Serum/plasma lipids were such as to increase the risk of cardiovascular disease in these subjects.

Iron status in women aerobic dance instructors.

This investigation evaluated the iron and nutritional status of 12 highly trained aerobic dance instructors who did not take iron supplements (ANS) and 8 who did (AS). A control group (C) consisted of 10 age matched controls. The aerobic instructors had exercised for approximately 3.8 days/wk, 56 min/session for the past 7 yrs. There were no significant differences among groups for energy intake, carbohydrate, protein, fat, nonheme iron, heme iron, or total iron intake (excluding supplemental iron). But both exercise groups had lower ferritin values than the control group. There was also a significant difference in mean cell volume (MCV), with both exercise groups having greater values than the control group. There were no differences among groups for serum iron, total iron binding capacity, transferrin saturation, hematocrit, or hemoglobin. One in three aerobic dance instructors had serum ferritin values below 12 micrograms.L-1. Results indicate that women exercise leaders have iron profiles that are similar to other groups of female athletes. The increased MCV values suggest runners' macrocytosis or an exercise induced macrocytosis.

Efficacy of chromium supplementation in athletes: emphasis on anabolism.

As the biologically active component of glucose tolerance factor (GTF), the essential trace mineral chromium is now being marked to athletes. GTF potentiates insulin activity and is responsible for normal insulin function. Thus, insulin's effects on carbohydrate, fat, and protein metabolism are dependent upon the maintenance of adequate chromium stores. Due to excessive chromium loss and marginal chromium intake, athletes may have an increased requirement for chromium. Therefore, in some circumstances the dietary supplementation of a chromium compound may be efficacious. The restoration and maintenance of chromium stores via supplementation would promote optimal insulin efficiency, necessary for high-level athletic performance. However, potential anabolic effects of enhanced insulin function would likely be marginal, and reports of short-term anabolic increases from the supplementation of an organic chromium compound need to be confirmed.

Neuropsychologic and postural sway improvement after Ca(++)-EDTA chelation for mild lead intoxication.

Neuropsychologic and postural sway test performance improved following Ca(++)-EDTA chelation in a bridge worker with persistent central nervous system (CNS) symptoms 2 years after an episode of subacute lead intoxication. This case highlights the value of these tests in verifying symptoms and documenting response to therapy. Persistent disabling CNS symptoms with objective neuropsychologic deficits was unexpected, given the borderline total body lead burden.

Calcium supplementation on normotensive and hypertensive pregnant women.

Normotensive and hypertensive pregnant women participated in a study to determine the effects of calcium supplementation on blood pressure. Subjects were randomly assigned to control or supplemented groups (1000 mg Ca/d). Blood pressure and serum total and ionic calcium were measured during the 20-wk supplementation period. Calcium supplementation had a significant lowering effect on diastolic blood pressure over the course of the study in the hypertensive group only. The hypertensive control subjects' mean serum ionic calcium value decreased significantly (P less than 0.05) over the course of the experiment. A significant (P less than 0.05) inverse relationship was observed between dietary calcium intake and blood pressure (r = -0.386 for systolic pressure and -0.359 for diastolic pressure).

The effect of diet, exercise and 7,12-dimethylbenz(a)anthracene on food intake, body composition and carcass energy levels in virgin female BALB/c mice.

This study investigated the effect of diet, exercise and , 7,12-dimethylbenz(a)anthracene (DMBA), a mammary-tumor carcinogen, on food intake, energy consumption, body weight and body composition in virgin female BALB/c mice. Interactions were examined among three diet conditions (standard AIN-76A, restricted AIN-76A and high fat AIN-76A diet), two exercise conditions (with and without treadmill exercise) and two treatment conditions (carcinogen or corn oil sham). Mice were randomized to one of 12 groups at 6 wk of age; beginning at 8 wk of age, all mice received either 7,12-dimethylbenz(a)anthracene (1 mg/0.2 mL corn oil) or 0.2 mL of corn oil via gastric tube once each week for six consecutive weeks. Exercise in a rotating-drum treadmill was initiated at 10 wk of age and was increased to a final rate of 6 m/min for 60 min, 5 d/wk. Mice were killed at 24 wk of age, confirmed to be tumor-free and analyzed for protein and fat content, from which body energy was calculated. Energy consumption was highest in the standard diet-fed groups followed by the high fat diet-fed groups and the restricted diet-fed groups. The groups fed the standard diet and restricted diet had similar body weight and carcass energy. Exercise or DMBA treatment generally reduced food consumption, energy intake, body weight and carcass energy. In summary, diet, exercise and DMBA all had pronounced effects on energy consumption, which in turn affected body composition. These treatments may influence expression of breast cancer via their effects on body composition.

Reduced energy intake and moderate exercise reduce mammary tumor incidence in virgin female BALB/c mice treated with 7,12-dimethylbenz(a)anthracene.

This study evaluated the concurrent effects of diet (standard AIN-76A, restricted AIN-76A and high-fat diet) and moderate rotating-drum treadmill exercise on the incidence of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in virgin female BALB/cMed mice free of murine mammary tumor virus. Exercise significantly reduced food consumption in the groups fed the standard diet and high fat diet. Although food consumption varied widely, final body weight was similar in all groups. Exercise had no effect on mammary tumor incidence in the standard diet-fed groups (without exercise, 47%; with exercise, 45%); however, exercise reduced mammary tumor incidence in the other groups as follows: restricted diet/no exercise, 28%; restricted diet/with exercise, 13%; high fat diet/no exercise, 31%; high fat diet/with exercise, 19%. Restricting food intake reduced mammary tumor incidence, but had no effect on body weight. Although energy intake was related to mammary tumor incidence, neither body weight nor dietary fat predicted tumor incidence.

Alterations in dietary carbohydrate, protein, and fat intake and mood state in trained female cyclists.

Seven highly trained female cyclists (age 22 +/- 5 yr, height 165 +/- 6 cm, weight 60 +/- 5 kg, VO2max 55 +/- 6 ml.min-1.kg-1, mean +/- SD) consumed, for 1 wk each, isocaloric diets containing varying levels of carbohydrate, protein, and fat designated as low carbohydrate (LCHO), moderate carbohydrate (MCHO), and high carbohydrate (HCHO). Diets were administered in random order, and each subject consumed all three diet treatments. At the end of each weekly diet treatment, subjects rode on a cycle ergometer at 80% VO2max until fatigued. Cyclists continued light training during the diet treatments. Following each diet treatment and immediately prior to the fatiguing cycle ergometer ride, cyclists completed a Profile of Mood States (POMS) questionnaire. The POMS yields measures of tension (T), depression (D), anger (A), vigor (V), fatigue (F), and confusion (C), as well as providing a total mood score (TMS). Results indicated that subjects on LCHO had significantly (P less than or equal to 0.05) greater T, D, A, and TMS and less V compared with MCHO and HCHO. There were no significant differences between MCHO and HCHO. In the present study, LCHO in conjunction with training and exercise adversely affected the mood state of trained female cyclists as compared with MCHO and HCHO diets.

Dietary status of trained female cyclists.

Dietary status was evaluated in eight highly trained female cyclists. Each cyclist kept a 3-day weighed food record. Diets were analyzed for nutrient content using a computerized software package. Blood was also obtained and evaluated for hemoglobin, hematocrit, and albumin. For an athletic group, the cyclists' diets were found to be low in energy (85% RDA) and carbohydrate (4.4 gm/kg body weight per day). Mean daily dietary intakes were well below the RDAs for folacin (76% RDA), magnesium (81%), iron (59%), and zinc (48%). In addition, more than one-third of the cyclists failed to consume 67% of the RDA for the following micronutrients: pyridoxine, folacin, cobalamin, vitamin E, magnesium, iron, and zinc. Hemoglobin (135 gm/L), hematocrit (0.39), and albumin (45 gm/L) values were all normal, although most hemoglobin values were in the lower 50% of normal range. Foods such as meats, poultry, fish, beans, peas, and nuts were low or absent from the diets of most athletes. Dietary quality in this group of female cyclists could have been greatly improved with the addition of more of those foods. These athletes could benefit from nutrition education and diet counseling.

Ascorbic acid status of smoking and nonsmoking adolescent females.

The nutritional status of a group of smoking (N = 11) and nonsmoking (N = 26) adolescent females, ages 14 to 17 years, was evaluated with respect to vitamin C. Dietary intakes of ascorbic acid (AA) were determined from two separate 24-hour food recalls. Plasma AA was determined via the 2,4-dinitrophenylhydrazine method. Significant differences were found between smokers and nonsmokers for vitamin C intake and plasma AA. Smokers had lower dietary intakes (27 +/- 11 mg/day) and plasma AA levels (0.32 +/- 0.19 mg/dl) than did nonsmokers (73 +/- 47 mg/day; 1.46 +/- 0.69 mg/dl). When plasma vitamin C values were adjusted for vitamin C intake, smokers still exhibited a significantly lower plasma AA concentration (0.48 mg/dl vs 1.38 mg/dl for nonsmokers). Cigarette smoking was associated with a significantly decreased AA status in the present group of adolescent females.

Lung function and treadmill performance of smoking and nonsmoking males receiving ascorbic acid supplements.

Twelve cigarette smoking and 10 nonsmoking healthy human volunteers, 25 to 38 yr of age, performed lung function and treadmill performance tests over two periods of 3 wk duration while taking either ascorbic acid (300 mg daily) or placebo tablets in a cross-over design. The two exercise periods were separated by a one-month inactive phase. Tablets were administered in a random, double-blind manner. Plasma vitamin C levels were significantly increased after 3 wk of ascorbic acid supplementation in both smokers and nonsmokers as compared to initial levels in the same subjects. No differences between ascorbic acid and placebo treatments of smokers and nonsmokers were observed for 1-s forced expiratory volume, forced vital capacity, 1-s forced expiratory percent, resting heart rate, resting and postexercise systolic and diastolic blood pressures, treadmill workload, postexercise blood lactic acid, and ventilation measurements. The postexercise systolic blood pressure values of the nonsmokers were lower, although not quite significantly, after the ascorbic acid treatment than after the placebo. The 300-mg ascorbic acid supplement appeared to have little effect on the lung function and physical performance of healthy smoking and nonsmoking males.

Nutritional status of white college students in Virginia.

The nutritional status of the fifty men, fifty-three women, and forty-seven women taking oral contraceptives--all white--between the ages of seventeen and twenty-two years--as reflected by height-weight measurements, hemoglobin-hematocrit values, and dietary records, was similar or slightly better than reported by other investigators. Low hemoglobin values were observed in 2 to 4 per cent of these students, and low hematocrits, in 8 to 17 per cent. Similar hemoglobin and hematocrit values were observed in all women, regardless of whether they were taking oral contraceptives. Exercise patterns; use of vitamin-mineral supplements, "pot," alcoholic beverages, special diets; whether subjects ate alone; where subjects ate; snacking; number of meals consumed daily; whether subjects had ever been diagnosed as being anemic; and what subjects thought of their food habits did not affect hemoglobin or hematocrit. Iron intakes of many of the women students were below the allowance.