A chronological expression profile of gene activity during embryonic mouse brain development.

The brain is a functionally complex organ, the patterning and development of which are key to adult health. To help elucidate the genetic networks underlying mammalian brain patterning, we conducted detailed transcriptional profiling during embryonic development of the mouse brain. A total of 2,400 genes were identified as showing differential expression between three developmental stages. Analysis of the data identified nine gene clusters to demonstrate analogous expression profiles. A significant group of novel genes of as yet undiscovered biological function were detected as being potentially relevant to brain development and function, in addition to genes that have previously identified roles in the brain. Furthermore, analysis for genes that display asymmetric expression between the left and right brain hemispheres during development revealed 35 genes as putatively asymmetric from a combined data set. Our data constitute a valuable new resource for neuroscience and neurodevelopment, exposing possible functional associations between genes, including novel loci, and encouraging their further investigation in human neurological and behavioural disorders.

Circulating thrombotic and haemostatic components in patients with coronary artery disease.

The study aimed to analyze the circulating levels of thrombotic and haemostatic components; tissue factor, tissue factor pathway inhibitor, tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with acute myocardial infarction at presentation (Group 1, n=49), unstable angina and Non-ST elevated MI after treatment (Group 2, n=22), stable angina (Group 3, n=18) and healthy individuals (Group 4, n=31). Significant finding was increase in tissue factor not only in Group 1 (2.0 fold, P=0.001), Group 2 (2.2 fold, P=0.015) but also in Group 3 (1.8 fold, P=0.018) as compared to controls. In Group 1 Plasminogen activator inhibitor-1 increased significantly (35.8%, P=0.02). Tissue factor pathway inhibitor and tissue plasminogen activator demonstrated increase in Group 1 of age<40 years while insignificant changes in elder patients. Increased thrombotic and decreased fibrinolytic conditions in acute myocardial infarction patients were observed. Increase TF in stable angina demonstrates procoagulant status in these patients as well.

Matrix metalloproteinase-3 (MMP-3) -1612 5A/6A promoter polymorphism in coronary artery disease in Indian population.

Matrix metalloproteinases (MMPs) play important role in the pathogenesis of coronary artery disease (CAD). 5A allele of -1612 5A/6A polymorphism of MMP-3 is associated with two fold higher activity than 6A allele. Present study was designed to analyse the association of this polymorphism with CAD in Indian population. Subjects included in the study were patients with stable angina (n=35), unstable angina (n=53), patients with recent event of myocardial infarction (MI) (MI Group-1, n=56) and patients at presentation of the acute MI (MI Group-2, n=49). Controls were healthy individuals (n=99). Genotyping of MMP-3 5A/6A polymorphism was carried out by PCR-based restriction digestion method. The genotype distribution of patient groups did not deviate from controls. Serum MMP-3 levels were significantly elevated at presentation of the acute MI by 36.8% (P=0.031) as compared to controls and more associated with 6A genotype suggesting discrepancy between in vitro transfection experiment and peripheral MMP-3 levels.

Insulin sensitivity as a risk factor for common carotid intima media thickness (IMT): its relation to atherosclerosis.

INTRODUCTION: The relationship between insulin resistance and atherosclerosis (ATH) in non-diabetic hypertensive patients from the Asian Indian population remains poorly understood. To resolve this issue, the present study was designed to analyze whether insulin sensitivity in a non-diabetic individual is related to the development of ATH.(by using IMT as an index) and whether this relationship is dependent on the presence of other cardiovascular disease (CVD) risk factors such as dyslipidemia and hypertension. METHODOLOGY: This study included 68 healthy controls with no diabetes and hypertension and 41 hypertensive patients who underwent four-point oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). A biochemical profile, beta mode ultrasonography for intima media thickness of carotid artery, and ECG determination was carried out. RESULTS: Hypertensive patients in our study exhibited significantly increased abdominal obesity. Blood pressure, fasting and 2 hr plasma glucose (4.62 +/- 0.08 and 5.55 +/- 0.17 mmol/l), and triglyceride (1.47 +/- 0.067 mmol/l) levels were compared to those of control subjects (p < 0.05). The fasting insulin levels and HOMA-IR were also significantly increased and Composite Insulin Sensitivity Index (CISI) reduced compared to controls with p < 0.01. Intima media thickness of the left (0.08 +/- 0.01) and right (0.069 +/- 0.008) CA were both significantly increased in hypertensives (p < 0.01). Correlation analysis showed that IMT of the left carotid artery was significantly associated with triglyceride levels (r = 0.813, p < 0.05) but not with insulin measures such as HOMA-IR and CISI. CONCLUSION: Hyperinsulinemia was observed in our non-diabetic hypertensive patients, but no association was found between IMT and insulin resistance. That IMT of hypertensives was associated with triglyceride levels suggests that high levels of insulin may be related to the development of ATH indirectly through its effects on lipid metabolism in our population.

Hypertension in the elderly.

OBJECTIVES: To study the clinical profile of hypertension in the elderly, development of end organ complications and the effect of hypertension with other risk factors in producing these complications. METHODS: One hundred and thirty six elderly patients attending the Hypertension Clinic were included in the study. A detailed history was taken that included presenting illness, family history of hypertension, diabetes, coronary artery disease, dyslipidaemia and history of addictions. Physical examination included systemic examination with measurement of waist to hip ratio and fundoscopy for retinopathy. Renal and liver function tests (RFT, LFT), blood sugar, lipid profile, X-ray chest, electrocardiography (ECG), 2-D echocardiography, abdominal ultrasound and computed tomography (CT) scan head (if indicated) were other important investigations done. RESULTS: Seventy-nine patients were in the age group of 60-65 years, of which 42 (30.9%) were males. Headache was the commonest chief complaint in 77.9% patients; whereas 24 patients were asymptomatic. Obesity, diabetes, alcohol, dyslipidaemia and family history were important determinants of hypertension. Lipid profile was abnormal in 55.9% patients. Isolated systolic hypertension (ISH) was found in 56.6% patients. Grade II hypertensive retinopathy was observed in 29.4% patients with uncontrolled blood pressure. Left ventricular hypertrophy (LVH) was the commonest ECG manifestation seen in 36.8% patients of which 26.5% had uncontrolled blood pressure. LVH could be diagnosed in 46.4% patients by 2-D echo. Patients with uncontrolled blood pressure and ISH had increased incidence of cardiovascular and cerebrovascular complications. Cardiovascular complications were seen in 19.1% patients having dyslipidaemia and hypertension. Cerebrovascular complications were seen in 15.4% patients having hypertension with LVH. Treatment included calcium channel blockers and/or other drugs. CONCLUSIONS: The elderly hypertensive patients tend to have ISH. Family history of hypertension is an important determinant of hypertension. Uncontrolled hypertension, ISH, LVH and other associated risk factors are responsible for cardiovascular and cerebrovascular morbidity.

Identification of persons at high risk of coronary heart disease--a mathematical formula based on biochemical, anthropometric and clinical markers.

A reliable method for identification of the subset of population predisposed to coronary heart disease (CHD) would aid a targetted implementation of intervention strategies. To this end, a mathematical formula was developed based on stepwise linear discriminant analysis. Age, body mass index, the number of associated coronary risk factors and a large number of biochemical markers were analysed by computerised discriminant analysis on a test sample of 203 subjects. Unstandardised canonical discriminant coefficients of statistically significant independent variables were used to derive the total discriminant score or the 'risk score'. The 'low-risk' persons not in need of immediate preventive measures of CHD could be distinguished from the 'high-risk' individuals with an almost 90% correctness. As compared with the existing methods such as clinical evaluation and cardiac stress test, the risk scores derived by the new method, and based chiefly on blood markers besides clinical and anthropometric variables, appeared to correctly predict the future coronary episodes in members of the test sample selected at random. The risk scores were also tested on a new sample of 50 subjects; while low scores were not associated with CHD, high scores in some patients were associated with myocardial ischemia. It appears that the preventive measures of CHD may be directed at people who have no clinical manifestations of CHD, but whose risk scores are greater than 0.1. On the other hand, if the score is less than -1.0, immediate preventive measures may not be necessary. If the score is between -1.0 and 0.1 (borderline), no immediate action may be taken but the score may be determined after six months, and action taken accordingly.

Triglyceride and coronary heart disease.

The predictive association of triglyceride (TG) in coronary heart disease (CHD). In patients without CHD levels were elevated in those coronary risk factors, as compared to those without the risk factor the elevation of TG may occur in asymptomatic subjects before the onset of clinical manifestation of CHD. The high-risk, asymptomatic subjects with high levels of TG may be on the "threshold" of the sysptomatic phase of CHD. The levels had a positive correlation with body mass index and increased with increasing number of coronary risk factors.

The coelomic cavity: an important site of materno-fetal nutrient exchange in the first trimester of pregnancy.

OBJECTIVE: To measure levels of folate and vitamin B12 in matched samples of amniotic fluid and extra-embryonic coelomic fluid from 9 to 12 weeks' gestation. DESIGN: Prospective observational study. SETTING: Homerton Hospital, London. SUBJECTS: Twenty-two women with ultrasonographically normal pregnancies before surgical termination. METHODS: Transvaginal ultrasound-guided needle aspiration of amniotic fluid and extra-embryonic coelomic fluid was performed. Pure samples of amniotic fluid and extra-embryonic coelomic fluid were obtained from each pregnancy, and folate and vitamin B12 were measured using microbiological assays. RESULTS: Levels of folate and vitamin B12 were higher in extra-embryonic coelomic fluid than in amniotic fluid and maternal serum. Amniotic fluid folate levels were lower than in maternal serum whereas vitamin B12 levels in amniotic fluid were higher than in maternal serum. All differences in concentration were significant (P < 0.0005; paired t-test). Positive correlations were found between the concentrations of folate and vitamin B12 in each fluid. There was a linear correlation between gestational age and amniotic fluid folate levels (r = 0.648; P = 0.001). CONCLUSIONS: High concentrations of folate and vitamin B12 in coelomic fluid suggest that the coelomic cavity plays an important role in the materno-fetal exchange of these nutrients.

Hypokalemic paralysis.

A case of Hypokalemic paralysis is reported which had an atypical onset and clinical features. The paralysis totally recovered on replacement of potassium.

Total anomalous pulmonary venous connection: asymptomatic survival for 50 years without surgical intervention.

Total anomalous pulmonary venous connection (TAPVC) is an uncommon cyanotic heart disease and survival beyond infancy is rare. We report a patient of TAPVC of the supracardiac variety who has survived till the age of 50 years without surgery.

Primary plasma cell leukaemia.

A rare form of plasma cell dyscrasia, primary plasma cell leukemia is presented. The clinical picture resembled an acute leukaemia with a fulminant course and a rapidly fatal outcome.