Commentary: Fetal origins of social situations? Medicalization of social life?
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Adult↗
Biomedical subjects
Yin Bun Cheung
Publications and source records attributed to Yin Bun Cheung.
A longitudinal study of pediatric body mass index values predicted health in middle age.
BACKGROUND AND OBJECTIVE: To characterize the use of pediatric body mass index (BMI) to predict obesity, overweight, and diseases in middle age. METHODS: A longitudinal study of people born in a week in 1958 (n=12,327). The main outcome measures are obesity (BMI > or = 30) and overweight (BMI > or = 25) at age 33 and disease history self-reported at age 42. Receiver operating characteristic (ROC) analysis was performed using BMI measured at ages 7, 11, and 16 years as predictors. RESULTS: BMI values measured at age 11 could predict obesity at age 33 with areas under ROC curve (AUC) of 0.78 for males and 0.80 for females (each P < .001). BMI values at age 11 predicted overweight with slightly smaller AUC (each P < .001). They could also predict history of diabetes and hypertension (AUC=0.60 and 0.56, respectively, each P < .01), both sexes pooled. Prediction based on BMI at age 7 was less satisfactory; that at 16 gave limited improvement. Cutoff points based on ROC curves, the international reference, and the 85th and 95th percentiles gave very different profiles of diagnostic features. CONCLUSION: Pediatric BMI may predict adult obesity and overweight with a reasonable profile of sensitivity and specificity.
Adolescent↗
CYP3A5*3 and *6 single nucleotide polymorphisms in three distinct Asian populations.
OBJECTIVE: To determine the frequencies of two functional single nucleotide polymorphisms, CYP3A5*3 and CYP3A5*6, in the CYP3A5 gene in three distinct Asian ethnic groups, namely, the Chinese, Malays and Indians. METHODS: Single nucleotide polymorphism analyses of CYP3A5*1, *3 and *6 were performed in 296 healthy subjects (108 Chinese, 98 Malays and 90 Indians) using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The *1 allele frequency was 25% in Chinese compared with 40% in Malays and Indians ( P=0.001). The *3 allele frequency was also higher in the Chinese population, being 76% versus 60% in the Malays and Indians ( P=0.001). The Malays and Indians also had allele frequencies significantly different from Caucasian, Japanese and African-American populations (each P<or=0.001) previously published in the literature. The *6 allele was not detected in any the three Asian ethnic groups analysed. CONCLUSION: These results seem to suggest that genetic polymorphisms in CYP3A5 in Asians, in particular Malays and Indians but also Chinese although to a lesser extent, may be an important genetic contributor to interindividual as well as interethnic differences in clearance of CYP3A substrates.
Asian People↗
Age at diagnosis and the choice of survival analysis methods in cancer epidemiology.
A young age at diagnosis of cancer is often seen as an indicator of the aggressiveness of the tumor. However, empirical studies have shown conflicting results on the association between age at diagnosis and survival. There are two choices of time scale for a Cox regression model: time since diagnosis, and age. The regression analysis of relative survival rates is an alternative to the Cox model. Using breast cancer data from a population-based cancer registry, we illustrate the features of Cox models using the two time scales and compare them with the relative survival approach. Using a Cox model with time since diagnosis as the time scale, a younger age at diagnosis is associated with a lower mortality; using age as the time scale gives the opposite result. The relative survival approach agrees with the Cox model with age as the time scale. We maintain that a careful clarification of research purpose and a careful choice of methods are necessary.
Adult↗
Growth in early life and its relation to pubertal growth.
BACKGROUND: The timing and magnitude of pubertal growth in relation to fetal, infancy and childhood growth have not been explored. METHODS: We used data from a longitudinal growth study of 3650 full-term healthy children who were born in Gothenburg, Sweden in 1973-1975. This analysis included 2738 children with height and weight measurements available both in early life and during adolescence. RESULTS: We found that faster linear growth during infancy and childhood was associated with earlier peak height velocity during adolescence. In contrast, greater height and body mass index (BMI) at birth were associated with later peak height velocity in adolescence. Children with faster linear growth and greater BMI in infancy and childhood had less height gain between ages 8 and 18. However, greater height and BMI at birth were associated with more height gain between ages 8 and 18 after adjusting for height and BMI in childhood. CONCLUSIONS: Both length and BMI (at birth, in infancy and during childhood) are associated with the timing and magnitude of pubertal growth. Being small at birth is associated with early puberty and a reduced height gain during adolescence.
Adolescent↗
Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients.
Intestinal cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) both play a vital role in the metabolism of oral cyclosporine (CsA). We investigated the genetic polymorphisms in CYP3A4(promoter region and exons 5, 7 and 9) and MDR1 (exons 12, 21 and 26) genes and the impact of these polymorphisms on the pharmacokinetics of oral CsA in stable heart transplant patients (n = 14). CYP3A4 polymorphisms were rare in the Asian population and transplant patients. Haplotype analysis revealed 12 haplotypes in the Chinese, eight in the Malays and 10 in the Indians. T-T-T was the most common haplotype in all ethnic groups. The frequency of the homozygous mutant genotype at all three loci (TT-TT-TT) was highest in the Indians (31%) compared to 19% and 15% in the Chinese and Malays, respectively. In heart transplant patients, CsA exposure (AUC(0-4 h), AUC(0-12 h) and C(max)) was high in patients with the T-T-T haplotypes compared to those with C-G-C haplotypes. These findings suggest that haplotypes rather than genotypes influence CsA disposition in transplant patients.
Administration, Oral↗
A confirmatory factor analysis of the 12-item General Health Questionnaire among older people.
BACKGROUND: the 12-item General Health Questionnaire (GHQ) is useful in measuring psychiatric morbidity in older people. Previous studies of its factor structure were often based on samples of young persons and on exploratory factor analysis techniques. The results varied from suggesting one to three factors. METHODS: this study involved 2123 participants aged over 60 and 7490 younger adults in a population-based survey in Britain. It compared the relative plausibility of several factor structures proposed by previous researchers, as indicated by the Akaike's Information Criterion and the Non-Normed Fit Index. Correlation between factors and internal consistency were examined. Mean subscale scores by demographic characteristics were analysed by ANOVA for the best-fit model. RESULTS: the 3-factor structure proposed by Graetz gave the best fit in both older and younger people. The properties of this model in older people were examined in details. The patterns of internal consistency and between-factor correlation were found satisfactory. Differences and similarities in subscale scores between demographic groups e.g. marital status, were presented. CONCLUSION: the 12-item General Health Questionnaire may measure three aspects of mental health, namely Anxiety and Depression, Social Dysfunction, and Loss of Confidence.
Aged↗
Early origins and adult correlates of psychosomatic distress.
Previous studies have demonstrated associations between fetal insults and psychological and developmental outcomes in children and adolescents. It is not clear whether psychosomatic problems in adults also have early origins. This study involved full-term live-born singletons free of congenital anomaly in the 1970 British Birth Cohort Study. Birthweight, gestational age, maternal smoking, parental social class and birth order were recorded around the time of birth. Psychological and somatic distresses were measured by the Malaise Inventory at age 26. A number of socio-behavioural covariates were also measured at this time. Multiple (least square) regression analysis showed that birthweight standardised for gestational age had a "reverse J" relation with psychological distress (p < 0.05); gestational age was inversely related to psychological distress (each p < 0.05); levels of maternal smoking were positively related to both psychological distress and somatic distress (each p < 0.01). Logistic regression analyses of high levels of psychological distress and somatic distress gave similar results. The findings were not strongly affected by adjustment for various adult correlates. In supplementary analyses multiple imputation was used to handle loss to follow-up and missing values at age 26. Approximately, the same patterns of associations were found. The results support the hypothesis of a biological link between perinatal factors and psychological distress in adults. The strengths of the associations were compared with those between the outcome and adult correlates.
Adult↗
A limited sampling strategy for the estimation of 12-hour Neoral systemic drug exposure in heart transplant recipients.
BACKGROUND: Therapeutic drug monitoring of cyclosporine in heart transplant patients is used to monitor therapy and prevent rejection. Of the various methods available for performing therapeutic drug monitoring of cyclosporine, the method of limited sampling strategy for area under the concentration-time curve profiling has been used most widely recently. The process of identifying sparse data points to predict area under the concentration-time curve is essentially a variable selection problem, with the variables being the drug concentrations at the various timepoints. Although fitting more variables into a model will typically allow for a better prediction of area under the concentration-time curve, improving the prediction has to be traded-off against the desirability of using as few timepoints as possible. The objective of this study was thus to formulate a model that would provide a good prediction of area under the concentration-time curve based on a limited number of sampling points. METHODS: We studied 15 stable heart transplant patients (11 Chinese and 4 Indians). All patients were receiving Neoral-based immunosuppression. Whole blood samples for area under the concentration-time curve analysis were obtained at the following timepoints: pre-dose (C(0h)) and at 1, 2, 3, 4, 6 and 12 hours (C(1h), C(2h), C(3h), C(4h), C(6h), C(12h), respectively) post-dose during the first dosing interval. The linear trapezoidal rule was used to calculate the area under the concentration-time curve (AUC) from time 0 h to 12 h. Various limited sampling strategies, as well as Keown's formula, which was derived in renal transplant patients and used C(0h) and C(2h), were compared based on their capacity for reducing total error squared. RESULTS: C(4h) was found to be the single most predictive timepoint and explained 95.3% of AUC(0-12) variation. C(0h) and C(12h) explained 60% and 75.7% of the variation in AUC(0-12), respectively. The best 2-variable model identified by stepwise selection procedures included C(1h) and C(4h) as predictors, explaining 97.3% of the variation in total area under the concentration-time curve from time 0 h to 12 h. Using Keown's algorithm, the R(2) was only 80.9%. CONCLUSION: We recommend using C(1h) and C(4h) as surrogate markers of area under the concentration-time curve from time 0 h to 12 h in our heart transplant patients. Because C(1h) and C(4h) represent timepoints within the zone of highest variability for Neoral's absorption phase, a model incorporating these timepoints would be able to explain a greater degree of variability associated with the Neoral absorption profile.
Adult↗
Influence of multiple dose activated charcoal on the disposition kinetics of irinotecan in rats.
INTRODUCTION: The main clinical adverse effect of irinotecan (CPT-11) therapy is diarrhoea. Using a rat model, we attempted to study the effects of activated charcoal on the prevention of diarrhoea after a bolus dose of CPT-11, and also investigated the disposition kinetics of CPT-11 and its metabolite, SN-38, as well as SN-38 glucuronide (SN-38G) in the presence and absence of charcoal. MATERIALS AND METHODS: Male Sprague-Dawley rats were given a daily oral dose of activated charcoal (Ultracarbon, 2.5 g/kg daily for 5 days) 10 min before an i.v. bolus injection of CPT-11 (60 mg/kg daily for 5 days; total dose 300 mg/kg); the control group was given CPT-11 alone. The pharmacokinetics of CPT-11, SN-38 and SN-38G were determined in both groups of rats on day 1. The incidence of diarrhoea was monitored throughout the course of the study. RESULTS: There were no differences in the mean (+/- SD) C, (15.8 +/- 7.5 vs 12.1 +/- 3.3 microg/ml), t1/2 (2.2 +/- 0.7 vs 2.2 +/- 0.5 h), CL (5.7 +/- 2.1 vs 6.8 +/- 1.2 l/h/kg), Vd (1798 +/- 958 vs 2280 +/- 731 l/kg) or AUC0-infinity (11.8 +/- 3.9 vs 9.1 +/- 1.7 microg x h/ml) of CPT-11 after dosing with or without activated charcoal. Similarly, charcoal treatment had no effect on the disposition kinetics of SN-38 and SN-38G. A higher frequency of grade 3 diarrhoea was observed in the control group compared to the charcoal treatment group (log OR: -1.06; 95% CI: -2.25, 0.13) but this was only marginally statistically significant (p = 0.08). CONCLUSION: These results suggest that multiple oral doses of activated charcoal do not modulate the clearance of CPT-11 and SN-38 in rats. The implication is that activated charcoal alone may not be very effective in preventing CPT-11-induced diarrhoea.
Administration, Oral↗
Cheung et al. Respond to "Are Appearances Deceiving?"
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Journal Article↗
The modulation of irinotecan-induced diarrhoea and pharmacokinetics by three different classes of pharmacologic agents.
Diarrhoea is the major dose-limiting toxicity of irinotecan hydrochloride (CPT-11) in the clinical setting. This study was designed to evaluate the effects of different pharmacological agents in the modulation of CPT-11 induced diarrhoea in Sprague-Dawley rats. We studied the effects of intravenous valproic acid (VPA), ceftriaxone (CTX) and oral charcoal in the modulation of CPT-11 induced diarrhoea. Male Sprague-Dawley rats (n=7 per group) were given CPT-11 60 mg/kg as intravenous injection from day 1 to 5 (total dose 300 mg/kg) in all treatment groups. Group 1 (G1) rats only received CPT-11, group 2 to 6 (G2 to G6) rats received in addition to IV CPT-11 60 mg/kg, IV valproic acid (VPA) 200 mg/kg (G2), IV VPA 200 mg/kg + IV ceftriaxone (CTX) 100 mg/kg (G3), IV VPA 200 mg/kg + oral activated charcoal 250 mg administered twice daily (G4), IV CTX 100 mg/kg (G5) and oral charcoal 250 mg every 12 hourly (G6). We compared the pharmacokinetics of total CPT-11 and its metabolites and the frequency and grade of diarrhoea in each group of rats. There were no significant differences in the pharmacokinetic parameters of total CPT-11 between treatment groups (p>0.05). Cotreatment with CTX and charcoal resulted in a lower total SN-38G AUC0- infinity (p<0.05 and p<0.01, respectively). Cotreatment with CTX also resulted in a lower Cmax for total SN-38G compared to other groups (p<0.01). A higher frequency of grade 3 diarrhoea was observed in G1 rats compared to other groups. Co-treatment with VPA (log OR: -1.13; 95% CI: -1.85, -0.41) or CTX (log OR: -1.66; 95% CI: -2.43, -0.88) were found to be associated with a lower odds of grade 3 diarrhoea compared to control or charcoal treated groups. Our findings indicate that CPT-11 treated rats given VPA and CTX, either alone or in combination has similar effects in preventing high grade diarrhoea. Activated charcoal was not found to be effective in the prevention of high grade diarrhoea.
Administration, Oral↗