Interindividual and intraindividual variability in acetylation: characterization with caffeine

The degree of interindividual and intraindividual variability in acetylator activity was investigated with caffeine used as a probe of enzyme activity. Acetylator phenotype and relative N-acetyltransferase activity were estimated in 46 subjects by measuring the urinary ratio of two metabolites, AFMU/1-MX, after a single 300 mg oral dose of caffeine on five separate occasions. Thirty homozygous slow (rr) and 15 heterozygous rapid (Rr) acetylators were identified. The degree of interindividual variability in acetylator activity was observed to be a mean of 32% (range 27% to 36%) and 20% (range 11% to 29%) in the rr and Rr groups, respectively. The mean intraindividual variation on repetitive measurement was 19% (range 6% to 49%) in the rr and 14% (range 7% to 24%) in the Rr acetylator group. Four subjects had apparent changes in acetylator activity with time such that they were unable to be assigned to any one acetylator group. Two of these four subjects exhibited apparent homozygous rapid acetylator activity intermittently during the 5-week trial. This variability may explain, in part, some of the high degree of patient variability observed in the toxicity, efficacy, and drug-related disease associated with acetylated drugs and environmental toxins.     

Down's syndrome

We discuss the ethical, psychosocial, economic, and medical dimensions of the treatment and management of a child with Down's syndrome and a congenital heart defect.     

Lecithin: cholesterol acyltransferase in Down's syndrome

Based on earlier reports indicating that Down's syndrome may represent an atheroma-free human model, two groups of institutionalized subjects were compared with respect to various parameters of their plasma lipid transport system. One group of subjects was comprised of Down's syndrome subjects and the second, a group of mentally retarded individuals. Parameters measured included plasma cholesterol, triglyceride, HDL-cholesterol, apolipoprotein levels (A-I, B, C-III, and E), lecithin:cholesterol acyltransferase (LCAT) activity, body mass and blood pressure. Statistical analyses indicated no significant differences between the two groups except for the lower fractional rate of cholesterol esterification (% cholesterol esterified per hour, p = 0.0049) in the Down's syndrome subjects. Adjustment for the effects of body mass and age revealed no other significant differences between the two groups except for a lower molar rate of esterification (nmol cholesterol esterified X h-1 X ml-1, p less than 0.0063) in the Down's syndrome subjects. Additional differences between the two groups were revealed by partial correlational analyses of LCAT activity with the measured parameters or ratios of these parameters which suggests that the composition and/or metabolism of lipoproteins may differ between these two groups. Whether the lower LCAT activity and the other differences reflected by the correlational analyses contribute to the decreased incidence of atherosclerotic lesions in Down's syndrome remains to be elucidated.     

Down's syndrome: current screening techniques

Antenatal screening for Down's syndrome traditionally relied upon performing amniocentesis for karyotype on pregnant women aged 35 years and older. This method detects approximately 20% of all Down's syndrome pregnancies, with a false-positive rate of 4.3%. By incorporating maternal serum alpha-fetoprotein values as an additional screening parameter to maternal age, 28% of all Down's syndrome pregnancies may be diagnosed, with a 35% reduction in false-positive results. Other screening parameters such as maternal serum unconjugated estriol and human chorionic gonadotropin may eventually make it possible to detect more than 65% of pregnancies with chromosomally abnormal fetuses, without compromise in false-positive rates.     

Down's syndrome: a biopsychosocial perspective

This article examines the biological, psychological and social effects of Down's syndrome and disability on children who have this condition, and on their families or carers.     

Postrotary nystagmus response in children with Down's syndrome

The purpose of this study was to investigate the nystagmus response in school-age children with Down's syndrome. The 35 subjects were between 5 and 9 years of age and were enrolled in public school programs for the educable and trainable mentally retarded in the northern metropolitan areas of Utah. The Southern California Postrotary Nystagmus Test (SCPNT) was administered with slightly modified verbal instructions. Durations of nystagmus for the subjects with Down's syndrome were compared with Ayres' normative data from the SCPNT using a t-test for two independent means. Results indicated there was a significant reduction in the duration of nystagmus in the children with Down's syndrome when compared to Ayres' sample of normal children; however, there was no significant difference between males and females with Down's syndrome in duration of postrotary nystagmus.     

Swedish parents of children with Down's syndrome

Becoming parents of a child with Down's syndrome (DS) challenges the adjustment ability in parenthood. Individuals with higher sense of coherence (SOC) are supposed to manage stressors better than those with lower SOC. The aims of this study were to investigate parental self-perceived stress, SOC, frequency of gainful employment and amount of time spent on child care in Swedish DS parents (165 parents; 86 mothers, 79 fathers) and to compare those with control parents of healthy children (169 parents; 87 mothers, 82 fathers). The mean age of the children was 4.7 years. Parents responded to questionnaires separately including Hymovich's Parent Perception Inventory as stress measurement and Antonovsky's short version of the Orientation to Life. No differences concerning total employment rate were observed, but the DS mothers were more often employed part-time than control mothers. The DS parents did not spend more time on child care than the control parents and they did not differ in mean SOC score, but the DS parents perceived greater stress. The differences in stress, particularly between the DS and control mothers, were related to time-demanding areas. Parents with high SOC scores experienced significantly less self-perceived stress.     

Acute effects of caffeine on heart rate variability in habitual caffeine consumers

During the last years, heart rate variability (HRV) has become a promising risk factor for cardiovascular events. However, the effect of caffeine on HRV in habitual caffeine consumers has barely been investigated. Therefore, we treated 30 male habitual caffeine users in a randomized double-blinded crossover study design with either placebo, 100 or 200 mg caffeine orally and determined parameters of HRV under resting conditions and metronomic breathing. As result, we could not detect significant differences in HRV parameters up to 90 min after drug ingestion. We conclude that modest amounts of caffeine do not reveal negative nor positive effects on HRV within the first 90 min after drug ingestion in young and healthy habitual caffeine consumers. However, further research is necessary to determine the effects of caffeine on HRV in habitual caffeine users, healthy as well as suffering from diabetes, hypertension and postmyocardial infarction.     

Age of seizure onset in adults with Down's syndrome

In a cohort of 68 adults (35 males and 33 females) with Down's syndrome aged 29-83 years, a history of seizures was found in 26.5%. The overall mean age of onset of seizures was 37 years, males (22 years) being significantly younger than females (51 years). The age of onset was bimodally distributed, with the first peak occurring in the first two decades, and a late-onset peak occurring in the fifth and sixth decades. A strong association between Alzheimer's disease and seizures was confirmed. Of those with a history of seizures, those aged over 45 years were significantly more likely to develop Alzheimer's disease than those younger than 45. It is suggested that late-onset epilepsy in Down's syndrome is associated with Alzheimer's disease, while early-onset epilepsy is associated with an absence of dementia.