Hossein Yarandi

Influence of coagulation factor, vitamin K epoxide reductase complex subunit 1, and cytochrome P450 2C9 gene polymorphisms on warfarin dose requirements

The primary objective of this study was to determine whether variability in warfarin dose requirements is determined by common polymorphisms in genes whose products are involved in the pharmacodynamics and pharmacokinetics of warfarin, namely, the coagulation factors, vitamin K epoxide reductase complex subunit 1 (VKORC1), and cytochrome P450 (CYP) 2C9.

β1‐Adrenergic Receptor Polymorphisms and Antihypertensive Response to Metoprolol

Marked interpatient variability exists in blood pressure response to β‐blocker monotherapy. We tested the hypothesis that 2 common polymorphisms in the gene for β1‐adrenergic receptor are associated with antihypertensive response to metoprolol in patients with uncomplicated hypertension.

Beta1-adrenergic receptor polymorphisms and left ventricular remodeling changes in response to beta-blocker therapy.

OBJECTIVE Large variability exists in the improvement in left ventricular (LV) function from beta-blocker treatment. We hypothesized that polymorphisms at codon 389 (Arg389Gly) and 49 (Ser49Gly) in the beta1-adrenergic receptor (AR) gene were associated with LV reverse remodeling changes in response to beta-blocker therapy among heart failure patients. METHODS We prospectively enrolled 61 beta-blocker naive patients with systolic heart failure. Patients underwent baseline echocardiography followed by metoprolol CR/XL. The dose was doubled on a biweekly basis up to 200 mg/day or attainment of maximum tolerated dose. Echocardiography was repeated after the patient received the target or highest tolerated dose for 3 months. RESULTS Among patients with the Arg389Arg genotype, ejection fraction (EF) increased from 23+/-5 to 29+/-10 (P=0.008). Gly389 carriers did not demonstrate any significant change in EF (22+/-9 to 23+/-11; P=0.45). There was a significant between-group difference in EF by genotype (P=0.04). The Arg389Arg genotype was also associated with significantly greater reductions in LV end-diastolic and end-systolic diameters compared to Gly389 carriers. Patients with the Gly49 variant also had a significantly greater reduction in LV end-diastolic diameter compared to Ser49 homozygotes. Multiple regression analysis modeling revealed that the codon 389 polymorphism was a significant predictor of an improvement in EF and both codon 49 and 389 polymorphisms were significant predictors of final LV end-diastolic diameter. CONCLUSIONS Heart failure patients with the Arg389Arg genotype and Gly49 carriers had greater improvements in LV remodeling from beta-blocker treatment.

β‐adrenergic Receptor Polymorphisms and Responses during Titration of Metoprolol Controlled Release/extended Release in Heart Failure

β‐Blockers require careful initiation and titration when used in patients with heart failure. Some patients tolerate β‐blocker therapy initiation without difficulty, whereas in other patients this period presents clinical challenges. We tested the hypothesis that polymorphisms at codons 389 (Arg389Gly) and 49 (Ser49Gly) of the β1‐adrenergic receptor would be associated with differences in initial tolerability of β‐blocker therapy in patients with heart failure. We also tested whether polymorphisms in the β2‐adrenergic receptor, G‐protein αs subunit (Gsα), and cytochrome P450 (CYP) 2D6 genes or S‐metoprolol plasma concentrations were associated with β‐blocker tolerability.

The Digital Divide and urban older adults.

Computers and the Internet offer older adults opportunities and resources for independent living. However, many urban older adults do not use computers. This study examined the demographic, health, and social activities of urban older adults to determine variables that might predict the use and nonuse of computers in this population. A secondary data analysis was performed using the 2001 Detroit City-Wide Needs Assessment of Older Adults (n = 1410) data set. Logistic regression was used to explore potential differences in predictor variables between computer users and nonusers. Overall, computer users were younger (27%), had a higher level of education, were more likely to be employed, had an annual income greater than

Depression among southern rural African American women: A factor analysis of the Beck Depression Inventory-II

20 000, and were healthier and more active than nonusers. They also were more likely to have memberships in community organizations and do volunteer work. Preferred computer activities included conducting Internet searches, playing games, writing, and communicating with family members and friends. The results suggest significant differences in demographic and health-related characteristics between computer users and nonusers among urban older adults. Although about a quarter of participants in this study used computers, the Digital Divide continues to exist in urban settings for scores of others.

Evaluating in-home training for fathers of children with autism using single-subject experimentation and group analysis methods

Background:This is the first reported study involving a factor analysis of the Beck Depression Inventory-II, which was administered to a sample of southern rural African American women. Objective:To determine the factor structure of the Beck Depression Inventory-II using data collected from southern rural African American women. Methods:Using a correlational, descriptive design, 206 southern rural African American women were invited to participate in a face-to-face interview that occurred in a variety of community-based settings. Results:The factor analysis of the Beck Depression Inventory-II resulted in a two-factor solution. Symptoms such as pessimism and worthlessness loaded high on the first factor (cognitive). The second factor explained somatic-affective symptoms of depression, with factor loadings high on tiredness and fatigue and loss of energy. Conclusions:The application of the Beck Depression Inventory-II among African American people would generate needed information about how depressive symptoms may be expressed among them. Knowledge gained from this study promises to be useful for developing appropriate research studies and population-specific treatment approaches for this group of women.

Changes in Circulating Satiety Hormones in Obese Children: A Randomized Controlled Physical Activity-Based Intervention Study

BackgroundAutism, or the broader category of autistic spectrum disorder, is a complex developmental disability with uncertain etiologies that appears to be increasing in prevalence. Researchers have stated that training programs for children with autism are most effective when they are individualized, address communicative intent of child behaviors, and promote social reciprocity between children and individuals with whom they have regular contact. Yet, to date, most of what is known comes solely from studying mothers, who have traditionally been the most accessible parent. ObjectivesIn this study the mother–child in-home training program was modified and evaluated for its effects on the acquisition of training skills by fathers and on precommunication skills by the autistic children. MethodsFrequency counts of skills taught to fathers and targeted child behaviors were obtained from videotaped father–child play sessions. These data were analyzed for each father–child dyad by using graphs and visual analyses, which are integral parts of single-participant experimentation. This procedure was replicated across all of the father–child dyads. Data were then grouped and analyzed using the more traditional repeated measures analysis of variance. ResultsThe most significant findings were increases in father use of imitating with animation (p < .0001) and child initiating following training (p < .0004). Also noteworthy were significant increases in father responding (p < .0005) and child vocalizations (p < .05). DiscussionResults of the study indicate that the in-home training for fathers of children with autism was effective and valued by the participating families.

Association of CYP3A5 polymorphisms with hypertension and antihypertensive response to verapamil.

The aims of this study are to examine in children: (i) obesity‐related alterations in satiety factors such as leptin, ghrelin, and obestatin; (ii) the link between satiety factors and cardiometabolic risk factors; and (iii) the impact of a physical activity‐based lifestyle intervention on the levels of these satiety factors in the obese. We studied a total of 21 adolescents (BMI percentile, 99.0 ± 0.6 for 15 obese and 56.2 ± 1.1 for 6 lean). The obese subjects underwent a 3‐month randomized controlled physical activity‐based lifestyle intervention. Leptin, soluble leptin receptor (sOB‐R), ghrelin, and obestatin levels were determined as the primary outcome measures. Other markers of cardiometabolic disease such as inflammation and insulin resistance were also determined. Body composition was measured by dual‐energy X‐ray absorptiometry. The concentrations of ghrelin, obestatin, and sOB‐R were significantly lower in the obese children compared to the lean controls, whereas that of leptin was higher (all P < 0.05). Although intervention led to a net increase in obestatin (P < 0.01) and no change in ghrelin levels, the balance between ghrelin and obestatin (ratio of ghrelin to obestatin, G/O) decreased (P < 0.02). Intervention reduced leptin and increased sOB‐R (P < 0.01 for both). Significant associations between satiety factors and other cardiometabolic risk factors were also observed. Taken together, alterations in the levels of satiety factors are evident early in the clinical course of obesity, but physical activity‐based lifestyle intervention either prevented their continued increase or normalized their levels. These beneficial effects appear to aid in the maintenance of body weight and reduction in cardiovascular risk.

The Impact of Dyadic Social Support on Self-Efficacy and Depression After Radical Prostatectomy

In the CYP3A5 gene, the A>G (*3) and G>A (*6) polymorphisms result in severely decreased expression of CYP3A5 enzyme relative to a normal functional allele (*1). We sought to determine if the CYP3A5 genetic polymorphisms were associated with level of blood pressure (BP), risk of hypertension (HTN), and the antihypertensive response to verapamil. A total of 676 normotensive and hypertensive participants (mean age 49±8.2 years) from the Hypertension Genes study and 722 patients (mean age 66±9 years) from the International Verapamil/Trandolapril Study Genetic Substudy (INVEST‐GENES) were genotyped for CYP3A5 to test for associations with BP, HTN, and in the latter cohort, antihypertensive response to verapamil. CYP3A5 haplotypes were determined using PHASE 2, with any allele containing either (*3) or (*6) designated as non functional. In the HTN genes population, there were no significant differences based on the number of functional CYP3A5 alleles, in systolic blood pressure (SBP) or diastolic blood pressure (DBP) among the normotensive whites or blacks (all P⩾0.70) or in allele frequency between normotensives and hypertensives. In INVEST‐GENES, when controlled for baseline BP, race, age, and gender, untreated BP in carriers versus non carriers of a CYP3A5 functional allele was 158.2±13.7 and 154.8±13.7 (P=0.061), respectively. CYP3A5 functional allele status was marginally associated with the SBP response to verapamil in blacks (P=0.075) and Hispanics (P=0.056), but not in whites (P=0.40), with the effect being largely driven by higher SBP in the carriers of two functional alleles. There was no association with DBP response and CYP3A5 allele status. CYP3A5 genotype does not contribute importantly to BP or risk of HTN, but may influence response to calcium channel blockers in populations in which carrier status of two functional alleles is common.