The influence of maternal and infant nutrition on cardiometabolic traits: novel findings and future research directions from four Canadian birth cohort studies.

A mother's nutritional choices while pregnant may have a great influence on her baby's development in the womb and during infancy. There is evidence that what a mother eats during pregnancy interacts with her genes to affect her child's susceptibility to poor health outcomes including childhood obesity, pre-diabetes, allergy and asthma. Furthermore, after what an infant eats can change his or her intestinal bacteria, which can further influence the development of these poor outcomes. In the present paper, we review the importance of birth cohorts, the formation and early findings from a multi-ethnic birth cohort alliance in Canada and summarise our future research directions for this birth cohort alliance. We summarise a method for harmonising collection and analysis of self-reported dietary data across multiple cohorts and provide examples of how this birth cohort alliance has contributed to our understanding of gestational diabetes risk; ethnic and diet-influences differences in the healthy infant microbiome; and the interplay between diet, ethnicity and birth weight. Ongoing work in this birth cohort alliance will focus on the use of metabolomic profiling to measure dietary intake, discovery of unique diet-gene and diet-epigenome interactions, and qualitative interviews with families of children at risk of metabolic syndrome. Our findings to-date and future areas of research will advance the evidence base that informs dietary guidelines in pregnancy, infancy and childhood, and will be relevant to diverse and high-risk populations of Canada and other high-income countries.

Parental and child genetic contributions to obesity traits in early life based on 83 loci validated in adults: the FAMILY study.

BACKGROUND: The genetic influence on child obesity has not been fully elucidated. OBJECTIVE: This study investigated the parental and child contributions of 83 adult body mass index (BMI)-associated single-nucleotide polymorphisms (SNPs) to obesity-related traits in children from birth to 5 years old. METHODS: A total of 1402 individuals were genotyped for 83 SNPs. An unweighted genetic risk score (GRS) was generated by the sum of BMI-increasing alleles. Repeated weight and length/height were measured at birth, 1, 2, 3 and 5 years of age, and age-specific and sex-specific weight and BMI Z-scores were computed. RESULTS: The GRS was significantly associated with birthweight Z-score (P = 0.03). It was also associated with weight/BMI Z-score gain between birth and 5 years old (P = 0.02 and 6.77 × 10-3 , respectively). In longitudinal analyses, the GRS was associated with weight and BMI Z-score from birth to 5 years (P = 5.91 × 10-3 and 5.08 × 10-3 , respectively). The maternal effects of rs3736485 in DMXL2 on weight and BMI variation from birth to 5 years were significantly greater compared with the paternal effects by Z test (P = 1.53 × 10-6 and 3.75 × 10-5 , respectively). CONCLUSIONS: SNPs contributing to adult BMI exert their effect at birth and in early childhood. Parent-of-origin effects may occur in a limited subset of obesity predisposing SNPs.

Prenatal and early-life predictors of atopy and allergic disease in Canadian children: results of the Family Atherosclerosis Monitoring In earLY life (FAMILY) Study.

Prenatal and early-life environmental exposures play a key role in the development of atopy and allergic disease. The Family Atherosclerosis Monitoring In earLY life Study is a general, population-based Canadian birth cohort that prospectively evaluated prenatal and early-life traits and their association with atopy and/or allergic disease. The study population included 901 babies, 857 mothers and 530 fathers. Prenatal and postnatal risk factors were evaluated through questionnaires collected during the antenatal period and at 1 year. The end points of atopy and allergic diseases in infants were evaluated through questionnaires and skin prick testing. Key outcomes included atopy (24.5%), food allergy (17.5%), cow's milk allergy (4.8%), wheezing (18.6%) and eczema (16%). The association between infant antibiotic exposure [odds ratio (OR): 2.04, 95% confidence interval (CI): 1.45-2.88] and increased atopy was noted in the multivariate analysis, whereas prenatal maternal exposure to dogs (OR: 0.60, 95% CI: 0.42-0.84) and acetaminophen (OR: 0.68, 95% CI: 0.51-0.92) was associated with decreased atopy. This population-based birth cohort in Canada demonstrated high rates of atopy, food allergy, wheezing and eczema. Several previously reported and some novel prenatal and postnatal exposures were associated with atopy and allergic diseases at 1 year of age.

Empirical evaluation of the Q-Genie tool: a protocol for assessment of effectiveness.

INTRODUCTION: Meta-analyses of genetic association studies are affected by biases and quality shortcomings of the individual studies. We previously developed and validated a risk of bias tool for use in systematic reviews of genetic association studies. The present study describes a larger empirical evaluation of the Q-Genie tool. METHODS AND ANALYSIS: MEDLINE, Embase, Global Health and the Human Genome Epidemiology Network will be searched for published meta-analyses of genetic association studies. Twelve reviewers in pairs will apply the Q-Genie tool to all studies in included meta-analyses. The Q-Genie will then be evaluated on its ability to (i) increase precision after exclusion of low quality studies, (ii) decrease heterogeneity after exclusion of low quality studies and (iii) good agreement with experts on quality rating by Q-Genie. A qualitative assessment of the tool will also be conducted using structured questionnaires. DISCUSSION: This systematic review will quantitatively and qualitatively assess the Q-Genie's ability to identify poor quality genetic association studies. This information will inform the selection of studies for inclusion in meta-analyses, conduct sensitivity analyses and perform metaregression. Results of this study will strengthen our confidence in estimates of the effect of a gene on an outcome from meta-analyses, ultimately bringing us closer to deliver on the promise of personalised medicine. ETHICS AND DISSEMINATION: An updated Q-Genie tool will be made available from the Population Genomics Program website and the results will be submitted for a peer-reviewed publication.

What accounts for ethnic differences in newborn skinfold thickness comparing South Asians and White Caucasians? Findings from the START and FAMILY Birth Cohorts.

OBJECTIVE: South Asians are a high-risk group for type 2 diabetes and coronary heart disease. We sought to determine ethnic differences in newborn adiposity comparing South Asians (SA) to White Caucasians (Whites). METHODS: Seven hundred ninety pregnant women (401 SA, 389 Whites) and their full-term offspring from two birth cohorts in Canada were analyzed. Pregnant women completed a health assessment including a 75-g oral glucose tolerance test to assess for dysglycemia. Birthweight, length, waist and hip circumference, and triceps and subscapular skinfold thickness (a surrogate measure of body adiposity) were measured in all newborns. Multivariate regression was used to identify maternal factors associated with newborn skinfold measurements. RESULTS: South Asian women were younger (30.1 vs 31.8 years, P<0.001), their prepregnancy body mass index was lower (23.7 vs 26.2, P<0.0001) and gestational diabetes was substantially higher (21% vs 13%, P=0.005) compared with Whites. Among full-term newborns, South Asians had lower birthweight (3283 vs 3517 g, P=0.0001), had greater skinfold thickness (11.7 vs 10.6 mm; P=0.0001) and higher waist circumference (31.1 vs 29.9 cm, P=0.0001) compared with Whites. Risk factors for newborn skinfold thickness included South Asian ethnicity (standardized estimate (s.e.): 0.24; P<0.0001), maternal glucose (s.e.: 0.079; P=0.04) and maternal body fat (s.e.: 0.14; P=0.0002). CONCLUSIONS: South Asian newborns are lower birthweight and have greater skinfold thickness, compared with White newborns, and this is influenced by maternal body fat and glucose. Interventions aimed at reducing body fat prior to pregnancy and gestational diabetes during pregnancy in South Asians may favorably alter newborn body composition and require evaluation.

Lack of association between type 2 diabetes and major depression: epidemiologic and genetic evidence in a multiethnic population.

The positive association between depression and type 2 diabetes (T2D) has been controversial, and little is known about the molecular determinants linking these disorders. Here we investigated the association between T2D and depression at the clinical and genetic level in a multiethnic cohort. We studied 17,404 individuals from EpiDREAM (3209 depression cases and 14,195 controls) who were at risk for T2D and had both phenotypic and genotypic information available at baseline. The glycemic status was determined using the 2003 American Diabetes Association criteria and an oral glucose tolerance test. Major depressive episode during the previous 12 months was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria. Twenty single-nucleotide polymorphisms (SNPs) previously associated with T2D were genotyped using the cardiovascular gene-centric 50-K SNP array and were analyzed separately and in combination using an unweighted genotype score (GS). Multivariate logistic regression models adjusted for age, sex, ethnicity and body mass index were performed. Newly diagnosed impaired fasting glucose (IFG)/impaired glucose tolerance (IGT), T2D and dysglycemia status were not associated with major depression (0.30 ⩽ P ⩽ 0.65). Twelve out of twenty SNPs and the GS were associated with IFG/IGT, T2D and/or dysglycemia status (6.0 × 10(-35) ⩽ P ⩽ 0.048). In contrast, the 20 SNPs and GS were not associated with depression (P ⩾ 0.09). Our cross-sectional data do not support an association between T2D and depression at the clinical and genetic level in a multiethnic population at risk for T2D.

Impact of rosiglitazone on body composition, hepatic fat, fatty acids, adipokines and glucose in persons with impaired fasting glucose or impaired glucose tolerance: a sub-study of the DREAM trial.

AIMS: Thiazolidinediones reduce ectopic fat, increase adiponectin and reduce inflammatory adipokines, fatty acids and glucose in people with Type 2 diabetes. We aimed to measure these effects in people with impaired fasting glucose and/or impaired glucose tolerance. METHODS: After approximately 3.5 years of exposure to rosiglitazone 8 mg (n = 88) or placebo (n = 102), 190 DREAM trial participants underwent abdominal computed tomography and dual-energy X-ray absorptiometry scans. Visceral and subcutaneous adipose tissue areas, estimated hepatic fat content, total fat and lean mass were calculated and changes in levels of fasting adipokines, free fatty acids, glucose and post-load glucose were assessed. RESULTS: Compared with the placebo, participants on rosiglitazone had no difference in lean mass, had 4.1 kg more body fat (P < 0.0001) and 31 cm(2) more subcutaneous abdominal adipose tissue area (P = 0.007). Only after adjusting for total fat, participants on rosiglitazone had 23 cm² less visceral adipose tissue area (P = 0.01) and an 0.08-unit higher liver:spleen attenuation ratio (i.e. less hepatic fat; P = 0.02) than those on the placebo. Adiponectin increased by 15.0 µg/ml with rosiglitazone and by 0.4 µg/ml with placebo (P < 0.0001). Rosiglitazone's effect on fat distribution was not independent of changes in adiponectin. Rosiglitazone's effects on fasting (-0.36 mmol/l; P = 0.0004) and 2-h post-load glucose (-1.21 mmol/l; P = 0.0008) were not affected by adjustment for fat distribution or changes in adiponectin or free fatty acids. CONCLUSIONS: In people with impaired fasting glucose/impaired glucose tolerance, rosiglitazone is associated with relatively less hepatic and visceral fat, increased subcutaneous fat and increased adiponectin levels. These effects do not appear to explain the glucose-lowering effect of rosiglitazone.

An emerging double burden of disease: the prevalence of individuals with cardiovascular disease and cancer.

OBJECTIVE: Cardiovascular disease (CVD) and cancer are the two leading causes of death in the United States; at the same time, the number of survivors is increasing as therapies continue to improve. The primary objective of this study is to determine the prevalence and characteristics of individuals affected by both CVD and cancer. DESIGN AND SETTING: We conducted a prevalence study using the 2009 and 2010 national Behavioural Risk Factor Surveillance System population survey. Data from a random sample of individuals (aged 25-99 years) from all states were collected. All participants provided information regarding their CVD and cancer status. Multivariable regression identified associations between participants' characteristics and the prevalence of double disease burden. RESULTS: Amongst 442,964 study participants, the overall prevalence rates were 11% for CVD and 15% for cancer; 3% of participants reported being survivors of both CVD and cancer. The prevalence of CVD+cancer increased twofold by 65 years of age (odds ratio [OR] 2.4, 95% confidence interval [CI] 2.3-2.5) and doubled again at ≥75 years (OR 4.9, 95% CI 4.6-5.1) and was higher amongst men (OR 1.6, 95% CI 1.6-1.7), multiracial individuals (OR 1.8, 95% CI 1.5-2.0) and those without a high school diploma (OR 1.3, 95% CI 1.2-1.4). Amongst individuals with CVD, 25% also reported having cancer, whilst 19% of all cancer survivors reported having CVD. CONCLUSIONS: The prevalence of the double burden of disease increased with age; this is particularly important as the 'baby boomers' reach this high-risk age group. Future studies should explore potential common upstream or downstream mechanisms of CVD and cancer as well as public health strategies to cope with the double burden of disease.

Measures of body fat in South Asian adults.

BACKGROUND: South Asian people who originate from the Indian subcontinent have greater percent body fat (%BF) for the same body mass index (BMI) compared with white Caucasians. This has been implicated in their increased risk of type 2 diabetes and cardiovascular disease. There is limited information comparing different measures of body fat in this ethnic group. OBJECTIVES: The objectives of this study were: (1) to investigate the correlation of %BF measured by a foot-to-foot bioelectrical impedance analysis (FF-BIA) against the BOD POD, a method of air-displacement plethysmography, and (2) to determine the correlations of simple anthropometric measures, (that is, BMI, body adiposity index (BAI), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR)) against the BOD POD measure of body fat. METHODS: Eighty apparently healthy South Asian men and women were recruited from the community, and measurements of height, weight, WC, HC and body composition using Tanita FF-BIA and BOD POD were taken. RESULTS: The mean±s.d. age of participants was 27.78±10.49 years, 42.5% were women, and the mean BMI was 22.68±3.51 kg m(-2). The mean body fat (%BF) calculated by FF-BIA and BOD POD was 21.94±7.88% and 26.20±8.47%, respectively. The %BF calculated by FF-BIA was highly correlated with the BOD POD (Pearson's r=0.83, P<0.001), however, FF-BIA underestimated %BF by 4.3%. When anthropometric measures were compared with % BF by BOD POD, the BAI showed the strongest correlation (r=0.74) and the WHR showed the weakest (r=0.33). BAI generally underestimated %BF by 2.6% in comparison with %BF by BOD POD. The correlations of BOD POD with other measures of %BF were much stronger in subjects with a BMI >21 kg m(-2) than those with a BMI 21 kg m(-2). CONCLUSION: The FF-BIA and BAI estimates of %BF are highly correlated with that of BOD POD among people of South Asian origin, although both methods somewhat underestimate % BF. Furthermore, their correlations with % BF from BOD POD are significantly weakened among men and women with a BMI 21 kg m(-2).

Increased cardiovascular risk after pre-eclampsia in women with dysglycaemia.

AIMS: Compared with women with uncomplicated pregnancies, women with a history of pre-eclampsia have two to five times the risk of cardiovascular disease. It is not known whether this risk is related to albuminuria, a known cardiovascular risk factor that is part of the definition of pre-eclampsia and that often persists after delivery. Our objective was to determine if the high risk of cardiovascular disease in women with pre-eclampsia is accounted for by known cardiovascular risk factors including albuminuria. METHODS: We performed a cross-sectional analysis of 4080 dysglycaemic women enrolled in a large randomized controlled trial who provided an obstetric history and had at least one delivery. Blood pressure, height, weight, waist circumference and hip circumference were measured. An oral glucose tolerance test, lipids, an electrocardiogram and an albumin/creatinine ratio from a first morning urine sample were obtained. RESULTS: There were 3613 women with no history of pre-eclampsia during their pregnancies, 108 with severe pre-eclampsia and 359 with non-severe pre-eclampsia. Women with a history of severe pre-eclampsia had higher rates of previous cardiovascular disease than women with non-severe pre-eclampsia or women without pre-eclampsia (87, 72 and 72%, P = 0.0019). The high risk of previous cardiovascular disease in women with a history of severe pre-eclampsia (odds ratio 2.67, 95% CI 1.52-4.70) persisted after adjustment for albuminuria (odds ratio 2.74, 95% CI 1.55-4.83) and also after adjusting for other covariates including albuminuria (odds ratio 3.03, 95% CI 1.69-5.44). CONCLUSION: Even after accounting for cardiovascular risk factors including albuminuria, a history of severe pre-eclampsia is independently associated with a threefold higher risk of cardiovascular disease.

The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression.

Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21,932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case-control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 × 10(-4)) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity (I(2)=0%, P=0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (ß 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression.

Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study.

AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death. METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22). CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.

Glucose levels are associated with cardiovascular disease and death in an international cohort of normal glycaemic and dysglycaemic men and women: the EpiDREAM cohort study

AIMS: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death.METHODS AND RESULTS: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22).CONCLUSIONS: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.

Anthropometric measures and glucose levels in a large multi-ethnic cohort of individuals at risk of developing type 2 diabetes.

AIMS/HYPOTHESES: We determined: (1) which of BMI, waist circumference, hip circumference and WHR has the strongest association and explanatory power for newly diagnosed type 2 diabetes and glucose status; and (2) the impact of considering two measures simultaneously. We also explored variation in anthropometric associations by sex and ethnicity. METHODS: We performed cross-sectional analysis of 22,293 men and women who were from five ethnic groups and 21 countries, and at risk of developing type 2 diabetes. Standardised anthropometric associations with type 2 diabetes and AUC of glucose status from OGTT (AUC(OGTT)) were determined using multiple regression. Explanatory power was assessed using the c-statistic and adjusted r (2). RESULTS: An increase in BMI, waist circumference or WHR had similar positive associations with type 2 diabetes, AUC(OGTT) and explanatory power after adjustment for age, sex, smoking and ethnicity (p < 0.01). However, using BMI and WHR together resulted in greater explanatory power than with other models (p < 0.01). Associations were strongest when waist circumference and hip circumference were used together, a combination that had greater explanatory power than other models except for BMI and WHR together (p < 0.01). Results were directionally similar according to sex and ethnicity; however, significant variations in associations were observed among these subgroups. CONCLUSIONS/INTERPRETATION: The combination of BMI and WHR, or of waist circumference and hip circumference has the best explanatory power for type 2 diabetes and glucose status compared with a single anthropometric measure. Measurement of waist circumference and hip circumference is required to optimally identify people at risk of type 2 diabetes and people with elevated glucose levels.

Identifying women with severe angiographic coronary disease.

OBJECTIVES: To determine sex/gender differences in the distribution of risk factors according to age and identify factors associated with the presence of severe coronary artery disease (CAD). DESIGN: We analysed 23,771 consecutive patients referred for coronary angiography from 2000 to 2006. SUBJECTS: Patients did not have previously diagnosed CAD and were referred for first diagnostic angiography. OUTCOME MEASURES: Patients were classified according to angiographic disease severity. Severe CAD was defined as left main stenosis > or = 50%, three-vessel disease with > or = 70% stenosis or two-vessel disease including proximal left anterior descending stenosis of > or = 70%. Univariate and multivariate logistic regression was used to assess the association between risk factors and angina symptoms with severe CAD. RESULTS: Women were less likely to have severe CAD (22.3% vs. 36.5%) compared with men. Women were also significantly older (69.8 +/- 10.6 vs. 66.3 +/- 10.7 years), had higher rates of diabetes (35.0% vs. 26.6%), hypertension (74.8% vs. 63.3%) and Canadian Cardiovascular Society (CCS) class IV angina symptoms (56.7% vs. 47.8%). Men were more likely to be smokers (56.9% vs. 37.9%). Factors independently associated with severe CAD included age (OR = 1.05; 95% CI 1.05-1.05, P < 0.01), male sex (OR = 2.43; CI 2.26-2.62, P < 0.01), diabetes (OR = 2.00; CI 1.86-2.18, P < 0.01), hyperlipidaemia (OR = 1.50; CI 1.39-1.61, P < 0.01), smoking (OR = 1.10; CI 1.03-1.18, P = 0.06) and CCS class IV symptoms (OR = 1.43; CI 1.34-1.53, P < 0.01). CCS Class IV angina was a stronger predictor of severe CAD amongst women compared with men (women OR = 1.82; CI 1.61-2.04 vs. men OR = 1.28; CI 1.18-1.39, P < 0.01). CONCLUSIONS: Women referred for first diagnostic angiography have lower rates of severe CAD compared with men across all ages. Whilst conventional risk factors, age, sex, diabetes, smoking and hyperlipidaemia are primary determinants of CAD amongst women and men, CCS Class IV angina is more likely to be associated with severe CAD in women than men.

Clinical Applications of PET and PET-CT.

Positron emission tomography (PET) and PET/ computed tomography (CT) are emerging as important imaging techniques and their popularity is growing within the medical fraternity. Though PET has been a useful research tool for many decades its real growth into clinical applications has occurred in the last one decade or so. Currently its major use is in oncologic imaging. However it has a multitude of clinical applications in cardiology, neurology and psychiatry as well. In oncologic imaging, a major advantage of PET is that a single whole-body examination can provide accurate assessment of disease activity and spread. PET/CT amalgamates the functional information of PET with the structural details of the CT scan, thus greatly aiding in accurate staging, therapy response assessment and early detection of recurrent disease.

Retrospective Analysis of Thyroid Cancer Patients.

BACKGROUND: Thyroid cancer is a spectrum of neoplasms and manifests in varied forms. The issues related to presentation, management and outcome of patients with thyroid malignancy are highlighted. METHODS: Retrospective analysis of 70 patients and survival analysis for event free survival was done. RESULT: Papillary carcinomas constituted 88 percent followed by follicular cancers at nine percent of all cancers. Females were affected more than males in the ratio of 2.2: 1. Mean age of presentation for papillary cancer was 39 years and for follicular 50 years. Sixteen percent patients had regional and 10 percent distant metastases. Seventeen percent showed raised serum thyroglobulin and 29 percent had an abnormal whole body scan during the follow up. Relapse rate were similar in those receiving 30 mCi of radioiodine and in those receiving more than 30 mCi. CONCLUSION: The study shows that tumour marker thyroglobulin has higher negative predictive value. Overall prognosis for differentiated thyroid cancers is good.

Hepato-biliary Scintigraphy in diagnosis of Biliary Atresia.

BACKGROUND: Biliary Atresia and Neonatal Hepatitis are the two major causes of Persistent Neonatal Jaundice. Differentiation is done by biochemical and radiological tests. Radiological investigations use intra-or extra-hepatic biliary dilation for diagnosing biliary atresia but this is not always reliable. METHODS: 14 neonates with persistent conjugated hyperbilirubinemia who had undergone hepato-biliary scintigraphy were retrospectively evaluated and those having Extrahepatic Biliary Atresia were analyzed with reference to operative findings. RESULTS: 11 out of 14 had Extrahepatic Biliary Atresia during operation whereas 3 proved to be false positive. CONCLUSION: Mebrofenin hepato - biliary scintigraphy is a simple, safe, accurate and cost effective investigation for diagnosis of biliary atresia.