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Biomedical subjects

H Vora

Publications and source records attributed to H Vora.

12 recordsLinked to original sources

Combined linkage and association analysis in pedigrees.

We applied a combined linkage and association model for quantitative traits in pedigrees to identify possible functional polymorphisms and to test for association resulting from population stratification and admixture. Functional polymorphisms are identified as variants that are significantly associated with a trait (high chi 2 value) and showing no residual evidence of linkage (low lod score). Applying our model to the simulated data in the population isolate (replicate 1) we correctly identified the polymorphism in gene 6 (MG1) that affects Q1. Without modeling association the lod score for Q1 was 5.4. At the site of the functional variant (5782 bp) the association chi 2 was 88.1 on 1 df (p < 0.001) and the lod score was 0.003. We estimated a 3.7-unit increase in the average Q1 for each extra copy of the polymorphism (95% CI = 2.95-4.41) and there was no evidence of population stratification or admixture (chi 2 = 0.08 on 2 df). For Q5 and gene 2, modeling the sequence variants at 11 loci simultaneously identified multiple functional variants. Including the main effect of 11 marker genotypes reduced the lod score at gene 2 from 8.7 to 0.9. Again, no evidence of population stratification or admixture was found (all chi 2 < 4.9 on 2 df; p > 0.05).

Adult↗

Maternal smoking during pregnancy, environmental tobacco smoke exposure and childhood lung function.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) during childhood and in utero exposure to maternal smoking are associated with adverse effects on lung growth and development. METHODS: A study was undertaken of the associations between maternal smoking during pregnancy, exposure to ETS, and pulmonary function in 3357 school children residing in 12 Southern California communities. Current and past exposure to household ETS and exposure to maternal smoking in utero were assessed by a self-administered questionnaire completed by parents of 4th, 7th, and 10th grade students in 1993. Standard linear regression techniques were used to estimate the effects of in utero and ETS exposure on lung function, adjusting for age, sex, race, Hispanic ethnicity, height, weight, asthma, personal smoking, and selected household characteristics. RESULTS: In utero exposure to maternal smoking was associated with reduced peak expiratory flow rate (PEFR) (-3.0%, 95% CI -4.4 to -1.4), mean mid expiratory flow (MMEF) (-4.6%, 95% CI -7.0 to -2.3), and forced expiratory flow (FEF(75)) (-6.2%, 95% CI -9.1 to -3.1), but not forced expiratory volume in one second (FEV(1)). Adjusting for household ETS exposure did not substantially change these estimates. The reductions in flows associated with in utero exposure did not significantly vary with sex, race, grade, income, parental education, or personal smoking. Exposure to two or more current household smokers was associated with reduced MMEF (-4.1%, 95% CI -7.6 to -0. 4) and FEF(75) (-4.4%, 95% CI -9.0 to 0.4). Current or past maternal smoking was associated with reductions in PEFR and MMEF; however, after adjustment for in utero exposure, deficits in MMEF and FEF(75) associated with all measurements of ETS were substantially reduced and were not statistically significant. CONCLUSIONS: In utero exposure to maternal smoking is independently associated with decreased lung function in children of school age, especially for small airway flows.

Adolescent↗

Association between air pollution and lung function growth in southern California children.

Average growth of lung function over a 4-yr period, in three cohorts of southern California children who were in the fourth, seventh, or tenth grade in 1993, was modeled as a function of average exposure to ambient air pollutants. In the fourth-grade cohort, significant deficits in growth of lung function (FEV(1), FVC, maximal midexpiratory flow [MMEF], and FEF(75)) were associated with exposure to particles with aerodynamic diameter less than 10 micrometer (PM(10)), PM(2.5), PM(10)-PM(2.5), NO(2), and inorganic acid vapor (p < 0.05). No significant associations were observed with ozone. The estimated growth rate for children in the most polluted of the communities as compared with the least polluted was predicted to result in a cumulative reduction of 3.4% in FEV(1) and 5.0% in MMEF over the 4-yr study period. The estimated deficits were generally larger for children spending more time outdoors. In the seventh- and tenth-grade cohorts, the estimated pollutant effects were also negative for most lung function measures, but sample sizes were lower in these groups and none achieved statistical significance. The results suggest that significant negative effects on lung function growth in children occur at current ambient concentrations of particles, NO(2), and inorganic acid vapor.

Adolescent↗

A study of twelve Southern California communities with differing levels and types of air pollution. II. Effects on pulmonary function.

To study the possible chronic respiratory effects of air pollutants, we designed and initiated a 10-yr prospective study of Southern California public schoolchildren living in 12 communities with different levels and profiles of air pollution. The design of the study, exposure assessment methods, and survey methods and results related to respiratory symptoms and conditions are described in the accompanying paper. Pulmonary function tests were completed on 3,293 subjects. We evaluated cross-sectionally the effects of air pollution exposures based on data collected in 1986-1990 by existing monitoring stations and data collected by our study team in 1994. Expected relationships were seen between demographic, physical, and other environmental factors and pulmonary function values. When the data were stratified by sex, an association was seen between pollution levels and lower pulmonary function in female subjects, with the associations being stronger for the 1994 exposure data than the 1986-1990 data. After adjustment, PM10, PM2.5, and NO2 were each significantly associated with lower FVC, FEV1, and maximal midexpiratory flow (MMEF); acid vapor with lower FVC, FEV1, peak expiratory flow rate (PEFR), and MMEF; and O3 with lower PEFR and MMEF. Effects were generally larger in those girls spending more time outdoors. Stepwise regression of adjusted pulmonary function values for girls in the 12 communities showed that NO2 was most strongly associated with lower FVC (r = -0.74, p < 0.01), PM2.5 with FEV1 (r = -0.72, p < 0.01), O3 with PEFR (r = -0.75, p < 0.005), and PM2.5 with MMEF (r = -0.80, p < 0.005). There was a statistically significant association between ozone exposure and decreased FVC and FEV1 in girls with asthma. For boys, significant associations were seen between peak O3 exposures and lower FVC and FEV1, but only in those spending more time outdoors. These findings underline the importance of follow-up of this cohort.

Acids↗

Air pollution and bronchitic symptoms in Southern California children with asthma.

The association of air pollution with the prevalence of chronic lower respiratory tract symptoms among children with a history of asthma or related symptoms was examined in a cross-sectional study. Parents of a total of 3,676 fourth, seventh, and tenth graders from classrooms in 12 communities in Southern California completed questionnaires that characterized the children's histories of respiratory illness and associated risk factors. The prevalences of bronchitis, chronic phlegm, and chronic cough were investigated among children with a history of asthma, wheeze without diagnosed asthma, and neither wheeze nor asthma. Average ambient annual exposure to ozone, particulate matter (PM(10) and PM(2.5); [less than/equal to] 10 microm and < 2.5 microm in aerodynamic diameter, respectively), acid vapor, and nitrogen dioxide (NO(2)) was estimated from monitoring stations in each community. Positive associations between air pollution and bronchitis and phlegm were observed only among children with asthma. As PM(10) increased across communities, there was a corresponding increase in the risk per interquartile range of bronchitis [odds ratio (OR) 1.4/19 microg/m(3); 95% confidence interval (CI), 1.1-1.8). Increased prevalence of phlegm was significantly associated with increasing exposure to all ambient pollutants except ozone. The strongest association was for NO(2), based on relative risk per interquartile range in the 12 communities (OR 2.7/24 ppb; CI, 1.4-5.3). The results suggest that children with a prior diagnosis of asthma are more likely to develop persistent lower respiratory tract symptoms when exposed to air pollution in Southern California.

Adolescent↗

Factors influencing the identification of major genes in a complex disease genome scan.

A two-stage linkage strategy was employed to identify major genes for a simulated complex disease via a genome scan. The importance of several approaches for improving the ability to locate major genes has been illustrated. These approaches are: adjusting for covariates, ascertaining through multiple affected family members, increasing the sample size, and using multipoint linkage analysis.

Chromosome Mapping↗

Interrelationship of prolactin and its receptor in carcinoma of colon and rectum: a preliminary report.

The prolactin receptors (PRLR) were correlated with circulating prolactin and various clinicopathologic parameters to investigate its prognostic value in patients with colorectal cancer. The prolactin (by radioimmunoassay) and its receptors (by radioligand method) were estimated in a total of 71 male patients with colorectal cancer enrolled at the Gujarat Cancer and Research Institute, Ahmedabad. The patients were followed for a period of 3 years. We have observed that 51% colorectal tumors were PRLR+. Significant correlation was not observed between presence/absence of PRLR and clinicopathologic variables. Dukes' D patients were lost to follow-up after 2-3 months; therefore, the results of prognostic significance were analysed only in patients with Dukes' A, B, and C (N = 64). Statistically significant difference in overall survival was not observed when the patients were subgrouped according to the presence/absence of PRLR and according to the cutoff level (i.e., 2%). PRLR+ hyperprolactinemic (Prolactin > 20.0 ng/ml plasma) patients had better overall survival than that of patients with PRLR- hyperprolactinemia, although the difference was statistically nonsignificant. However, PRLR- hyperprolactinemia patients had a more unfavourable prognosis than that of their counterparts. A similar trend was observed in patients with Dukes' B and C disease. Our preliminary study suggests an unequivocal finding, that PRLR- with concomitant hyperprolactinemia probably characterises a subgroup of patients with aggressive colorectal cancer.

Adult↗

No effect of gender on lung mucociliary clearance in young healthy adults.

Lung mucociliary clearance (LMC) depends on age and it is adversely affected by cigarette smoking. When using the radioaerosol technique for measuring LMC the initial site of deposition of the radioaerosol within the lungs affects its rate of removal. Whether there is a difference in gender for LMC is still an open question. Forty-one (20 female, 21 male) healthy, non-smoking subjects had their lung mucociliary clearance measured using an objective, non-invasive radioaerosol technique. The male and female groups were closely matched for initial distribution of the radioaerosol. There was no statistical significant difference between males and females in the rate of clearance of inhaled radioaerosol over a 6 h observation period. When comparing the LMC of two groups although it is important to match them for age, smoking habits and initial topographical distribution of the tracer radioaerosol it does not seem essential to also match the two groups for gender.

Adult↗

Patients who consult with tiredness: frequency of consultation, perceived causes of tiredness and its association with psychological distress.

BACKGROUND: Few prospective studies have been carried out in primary care on patients presenting with tiredness. AIM: A study was undertaken to describe patients whose main complaint was fatigue or of being "tired all the time'. METHOD: Over one year, doctors in four practices in Lancashire, Mid-Glamorgan, Suffolk and Surrey recruited 220 patients aged 16 years or more presenting with fatigue, and matched them with a comparison group from their lists. The general health questionnaire, a fatigue questionnaire and an attribution questionnaire were used to measure outcomes over six months. General practice records of consultations were also examined. RESULTS: Patients consulting for tiredness attended the doctor significantly more frequently than the comparison group both in the six months before and after entering the study. The frequency of attending could not be related to the duration or severity of fatigue alone. The majority consulting with tiredness scored highly on the general health questionnaire but so also did patients with equivalent fatigue scores in the comparison group. The correlation between fatigue and general health questionnaire scores was close for those patients who still had high fatigue scores six months later than it was for patients on entry to the study. Six months following study entry 61% of patients perceived the cause of the tiredness to be physical, while 57% of doctors viewed the problem as psychological. A small number of patients changed their views during the six months follow up from physical to psychological attributions. CONCLUSION: Patients consulting for tiredness are likely to report symptoms of psychological distress and attend more frequently than other patients. They tend to view the problem as physical while their doctors view the problem as psychological. Having established that there is no physical problem, doctors may need to focus more on sharing ideas and explanations when patients complain of being "tired all the time'.

Adolescent↗

Patients with fatigue in general practice: a prospective study.

OBJECTIVE: To describe the characteristics of patients attending their general practitioners and complaining of fatigue or being "tired all the time." DESIGN: Prospective study of cohort aged 16 years and older with follow up at two weeks and by questionnaires at two and six months. SUBJECTS: 220 patients (164 women) with mean age 43 years and an age-sex matched comparison group. SETTINGS: Doctors and patients in four practices in Lancashire, Mid Glamorgan, Suffolk, and Surrey. MAIN OUTCOME MEASURES: General clinical data, results from standard group of laboratory tests, fatigue questionnaire, and 12 item general health questionnaire. RESULTS: Over twice as many patients with fatigue had high scores on the health questionnaire compared with the comparison group (156 (75%) v 69 (34%)). Results of laboratory tests were abnormal and contributed to the diagnosis in 19 patients. 59 out of 102 patients who responded had high fatigue scores six months later. Patients with persistent fatigue were more likely to have a history of anxiety or depression and to have had fatigue for more than three months on entry to the study. CONCLUSIONS: Women are particularly at risk of fatigue. The outcome is better if patients have had symptoms for three months or less or there is no history of emotional illness.

Adolescent↗

Effect of oral bronchodilators on lung mucociliary clearance during sleep in patients with asthma.

BACKGROUND: Lung mucociliary clearance rates are reduced during sleep in patients with asthma. Methylxanthines and beta 2 agonists have been shown to enhance rates of lung mucociliary clearance. This study examined whether oral slow release bronchodilators may also have an effect on this clearance mechanism during sleep in patients with asthma. METHODS: Nine patients with asthma with a mean(SE) age of 65(5) years and percentage predicted forced expiratory volume in one second (FEV1 of 61(9)% participated in a double blind, placebo controlled, within subject crossover study to assess the effect of two weeks of treatment with salbutamol (Volmax; 8 mg twice daily) or theophylline (Phyllocontin; 350 mg twice daily) on lung mucociliary clearance during sleep. Lung mucociliary clearance rates were measured by a radioaerosol technique. RESULTS: The observation period for radioaerosol clearance was approximately 0.3 hours before sleep, 6.0 hours during sleep and 0.6 hours after sleep. Mean mucociliary clearance rates for theophylline, placebo and salbutamol before sleep were: 39, 39, and 32%/hour respectively; during sleep: 11, 10, and 9%/hour respectively; and after sleep: 39, 32, and 35%/hour respectively. CONCLUSION: During sleep lung mucociliary clearance in stable asthma was reduced, which is in agreement with the group's previous findings. Treatment with controlled/slow release oral bronchodilators had no effect on this reduced rate of clearance associated with sleep.

Aged↗

Tracheobronchial clearance in patients with bilateral diaphragmatic weakness.

Tracheobronchial clearance was measured in seven patients with bilateral diaphragmatic weakness using a noninvasive objective radioaerosol technique. The data were compared with those from seven healthy nonsmoking control subjects matched for physical characteristics and studied under the same experimental conditions; the control subjects were drawn from a data bank of healthy subjects and were matched to the patients for age, sex, and the initial distribution of their radioaerosol deposition. Pulmonary function indices (FEV1, FVC, PEFR, and MMFR25-75) for the patients were all significantly (p less than 0.01) reduced compared with those for the control subjects. The initial topographic distribution of the radioaerosol within the lungs of the patients and control groups was similar: alveolar deposition [mean (SD)] was 36.4 (6.7) versus 41.0 (4.0)%, and penetration index was 0.56 (0.08) versus 0.56 (0.03), respectively. Tracheobronchial clearance of deposited radioaerosol over a 6-h observation period after inhalation showed a marked reduction (p less than 0.02) in the patients: area under the clearance curve (between zero and 6 h) was 262 (80)% h for the patients and 142 (41)% h for the healthy control subjects. These data suggest that in patients with bilateral diaphragmatic weakness, mucociliary clearance is depressed, or that reduced mechanical movement of the lungs can itself impair clearance of secretions from the lungs. Impaired clearance from either cause may contribute to an increased incidence of chest infections in severe respiratory muscle weakness.

Adult↗