Interdistrict variations in child health status and health services utilization: lessons for health sector priority setting and planning from a cross-sectional survey in rural India.

BACKGROUND: There are limited data on interdistrict variations in child health status and health services utilization within the states of India. We conducted this study to identify and understand district-wise variations in child morbidity, mortality, healthcare seeking, and the status of health facilities in India. METHODS: A cross-sectional population-based cluster survey was conducted from April to July 2007 in 16 districts of eight states in India. Two districts with similar demographic profile and health criteria were selected from each study state. RESULTS: A total of 216 794 households and 24 812 under-5 children were surveyed. There were wide interdistrict variations in the health status of children within the same state and between different states across India. Interdistrict difference of >5 points/1000 live-births was found for infant mortality rate and under-5 mortality rate in all eight study states, while in six out of eight states this difference was >10 points/1000 live-births. Four states had a difference of >10 points/1000 live-births between respective districts for neonatal mortality rate. The interdistrict differences were also noted in childhood morbidity and health-seeking behaviour. Analysis of proportion of health facilities conforming to Indian public health standards revealed that the difference was m10% for availability of vaccines in five states, emergency services in three, laboratory services and logistics in four each, and referral facility in three of the eight study states. CONCLUSION: This study underscores an important information gap in the country where planners seem to rely heavily on a few selected national-level databases that may not be adequate at the micro level. The current process of sporadic health surveys also appears inadequate and inappropriate. There is a need for district-specific data for planning, improving quality of service and generating demand for health service utilization to improve child survival in India. The findings of this study may prove useful for child health programme planning in India.

Noncultured extracted hair follicle outer root sheath cell suspension for transplantation in vitiligo.

BACKGROUND: Current noncultured cell-based transplantation therapies for vitiligo largely involve shave skin biopsy for preparation of noncultured melanocyte suspension. As the overall proportion of melanocytes is low in the epidermis, these techniques require basal cell layer enrichment, which adds additional steps. We tried follicular unit extraction (FUE) to harvest hair follicles as a source of melanocytes. OBJECTIVES: To evaluate the efficacy of a novel surgical method for vitiligo: noncultured extracted hair follicular outer root sheath (ORS) cell suspension transplantation. METHODS: Fourteen patients with vitiligo, stable for at least 3 months, were included in this prospective study. Fifteen to 25 hair follicles were extracted from occipital scalp using the FUE method. Hair follicles were incubated with trypsin-ethylenediamine tetraacetic acid solution at 37°C for 90 min to separate ORS cells. The cell suspension was filtered through a 70-µm cell strainer, then centrifuged for 5 min at 1000 r.p.m. to obtain a cell pellet. The pellet was resuspended and applied to the dermabraded recipient area and dressed. RESULTS: The mean ± SD repigmentation was 65·7 ± 36·7%. Overall, nine of 14 patients achieved > 75% repigmentation. Mean percentage repigmentation was significantly higher in patients with ≥ 1 year stability than those with < 1 year stability (P = 0·02). CONCLUSIONS: Extracted hair follicular ORS cell suspension can be a useful simplified transplantation method for vitiligo. The transplantation procedure should be reserved for patients with vitiligo stable for at least 1 year. A larger study is needed for further evaluation.

Subcutaneous zygomycosis: report of 10 cases from two institutions in North India.

BACKGROUND: Subcutaneous zygomycosis is an uncommon condition observed in tropics. Few series have been published, particularly from the northern regions of India. OBJECTIVES: The aim of this study was to describe clinical, investigative and therapeutic details in subcutaneous zygomycosis observed in two teaching hospitals in Delhi. PATIENTS AND METHODS: Ten patients seen over a period of 10 years (1999-2009) form the material for this report. RESULTS: There were four children and six adults. In four children, the presentation was a subcutaneous localized mass or gradually spreading plaque. In the others, it was observed over nasal region of face, spreading inward into mucosal sites and paranasal sinuses, and outward to the contiguous areas. Regional lymphadenopathy was present in two with facial lesions. Majority showed a granulomatous infiltrate with admixture of other cells, mainly eosinophils. Aseptate or poorly septate hyphae were observed in seven. In one patient in whom no hyphae were observed, there was dense perivascular inflammation. Organisms were cultured from four patients, Basidiobolus ranarum in two and Syncephalastrum racemosum in two. The main therapy used was a saturated solution of potassium iodide (KI). Four received only KI of which two attained cure after 3 months and 9 months respectively, and the other two showed signs of regression. In one boy subsidence was associated with reduced circumference of thigh. Ketoconazole or itraconazole was given with KI to hasten regression when response was slow or there were side-effects to KI. CONCLUSION: Awareness and early recognition will prevent disfigurement produced by advanced disease, misdiagnosis and unnecessary surgical intervention.

Does cardiologist- or radiographer-operated fluoroscopy and image acquisition influence optimization of patient radiation exposure during routine coronary angiography?

The operator of radiation exposure during coronary angiography varies between different centres. The purpose of this study was to explore whether radiation dose was lower during cardiologist- or radiographer-controlled radiation exposure and to determine if the grade of cardiologist performing angiography influenced radiation dose. Patients were randomly allocated either to cardiologist- or radiographer-controlled radiation exposure during coronary angiography. Screening time and radiation dose during fluoroscopy and image acquisition, measured by dose-area product meter, were recorded. Mean radiation dose during cardiologist-controlled radiation exposure (n=176) of 15.6 Gy cm(2) (95% confidence interval (CI), 14.4-16.8) was significantly lower than that produced by the radiographer-controlled group (n=192) of 17.3 Gy cm(2) (95% CI, 16.2-18.6) (p<0.044). There was no significant difference in screening times produced by the two groups of radiation exposure operators. The difference in radiation dose produced by the two operator groups was principally owing to exposure produced at image acquisition. Irrespective of radiation exposure operator, consultant cardiologists produced significantly lower screening times and radiation doses compared with registrars. During routine coronary angiography, radiographer-controlled radiation exposure does not reduce screening time or radiation dose. Senior cardiologists produce the lowest radiation doses during coronary angiography when they are responsible for radiation exposure.

Sequential proton MRS study of brain metabolite changes monitored during a complete pathological cycle of demyelination and remyelination in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model.

Metabolite changes in rat brain internal capsule (ic) area were monitored using volume localized in vivo proton MR spectroscopy (MRS) in a lysophosphatidyl choline (LPC)-induced experimental demyelinating lesion model of multiple sclerosis (MS), during the early phase (pre-acute) as well as during the complete pathological cycle of de- and re-myelination processes. The N-acetyl aspartate (NAA) peak showed reduction during the early phase of the lesion progression (demyelination) until day 10 and increased thereafter during remyelination. However, choline (Cho) and lipid resonances showed increased signal intensity during the early phase and decreased during remyelination. A progressive reduction of the NAA/Cr metabolite ratio in lesioned rats was observed during demyelination (up to day 10) compared with before lesion (control), and the value increased thereafter during remyelination (from day 15). During this period, however, the Cho/Cr ratio was a higher until day 10 and subsequently declined and was close to that calculated before lesion creation. The changes in NAA/Cr and Cho/Cr metabolite ratios correspond to changes in the individual metabolite peaks such as NAA and Cho. The increase in the intensity of the choline resonance during the early phase is indicative of the onset of an inflammatory demyelination process, and its rapid decrease thereafter is due to reduction in the inflammatory process associated with remyelination. Similarly, the increase in the intensity of lipids during the pre-acute stage of the lesion is attributed to active demyelination, which significantly decreased during remyelination. These MR results correlate well with the histology data obtained.

Distinct changes in intranuclear lamin A/C organization during myoblast differentiation.

Intranuclear lamin foci or speckles have been observed in various cell types. In order to explore the possibility of changes in internal lamin organization during muscle differentiation, we have examined the appearance of A-type lamin speckles that associate with RNA splicing factor speckles in C2C12 myoblasts and myotubes. Lamin speckles were observed in dividing myoblasts but disappeared early during the course of differentiation in postmitotic myocytes, and were absent in myotubes and muscle fibers. However, no changes were seen in the typical peripheral organization of lamins A/C or B1 or in RNA splicing factor speckles. Lamin speckles were also absent in quiescent myoblasts but reappeared as cells were reactivated to enter the cell cycle. These changes were not observed in other quiescent cell types. Immunoblot analysis indicated that the abundance and migration of lamins A and C was not altered in differentiated myoblasts. When myotube or quiescent myoblast nuclei were extracted with nucleases and detergent, a uniformly stained internal lamina was revealed, indicating that lamins A/C were antigenically masked in these cells, probably owing to structural reorganization of the lamina during differentiation or quiescence. Our results suggest that muscle cell differentiation is accompanied by regulated rearrangements in the organization of the A-type lamins.

New-onset palpitations in general practice: assessing the discriminant value of items within the clinical history.

BACKGROUND: Palpitations are non-specific, with less than half of patients experiencing palpitations having a cardiac arrhythmia. Currently it seems that there is little evidence available to assist GPs in discriminating between patients complaining of palpitations who have significant cardiac arrhythmias and those who do not. OBJECTIVES: Our aim was to estimate discriminant functions for specific items of clinical information in relation to the categorization of a patient (aged over 18 years) with a symptom of new-onset palpitations presenting to primary care. METHODS: A network of 62 GPs spread amongst 36 practices agreed to recruit patients with new-onset palpitations over the course of a 9-month study period. Patients consenting to be involved in the study were asked a number of questions, focusing particularly on the medical history, and were requested to complete a Hospital Anxiety and Depression Scale. Each patient was also provided with a RhythmCard cardiac event recorder for up to 2 weeks and was asked to record their heart rhythm if they experienced palpitations. Odds ratios (adjusted for age and sex) were used to compare the clinical information obtained from patients with the final diagnosis. RESULTS: Of the 139 patients with palpitations presenting to GPs, it would appear that males [odds ratio = 2.1 (1.0-4.5)], those with regular palpitations [odds ratio = 2.5 (1.0-5.8)], those experiencing palpitations at work [odds ratio = 3.0 (1.3-7.2)] and those experiencing palpitations affected by sleeping (odds ratio = 3.3 (1.4-7.7)] were more likely to have a cardiac cause for their palpitations. Similar findings were made in an analysis focusing solely on the 81 patients with a RhythmCard result. Furthermore, amongst this group, it is interesting to note that patients with regular palpitations were more than twice as likely to have a 'significant' cardiac arrhythmia as a cause for their palpitations. There were suggestions of dose-response effects between the rate of the palpitation, the duration of the palpitation and the likelihood of it being a 'significant' arrhythmia. CONCLUSIONS: This study provides some information on the characteristics of patients reporting palpitations to GPs who may have 'significant' cardiac arrhythmias. Based on this work, we believe that a larger community-based study would be worthwhile and would provide useful and useable clinical discriminant information for GPs in the settings where they work and amongst the types of patients they encounter.

What is the optimal medical management of ischaemic heart failure?

Ischaemic heart disease is probably the most important cause of heart failure. All patients with heart failure may benefit from treatment designed to retard progressive ventricular dysfunction and arrhythmias. Patients with heart failure due to ischaemic heart disease may also, theoretically, benefit from treatments designed to relieve ischaemia and prevent coronary occlusion and from revascularisation. However, there is little evidence to show that effective treatments, such as angiotensin converting enzyme (ACE) inhibitors and beta-blockers, exert different effects in patients with heart failure with or without coronary disease. Moreover, there is no evidence that treatment directed specifically at myocardial ischaemia, whether or not symptomatic, or coronary disease alters outcome in patients with heart failure. Some agents, such as aspirin, designed to reduce the risk of coronary occlusion appear ineffective or harmful in patients with heart failure. There is no evidence, yet, that revascularisation improves prognosis in patients with heart failure, even in patients who are demonstrated to have extensive myocardial hibernation. On current evidence, revascularisation should be reserved for the relief of angina. Large-scale, randomised controlled trials are currently underway investigating the role of specific treatments targeted at coronary syndromes in patients who have heart failure. The CHRISTMAS study is investigating the effects of carvedilol in a large cohort of patients with and without hibernating myocardium. The WATCH study is comparing the efficacy of aspirin, clopidogrel and warfarin. The HEART-UK study is assessing the effect of revascularisation on mortality in patients with heart failure and myocardial hibernation. Smaller scale studies are currently assessing the safety and efficacy of statin therapy in patients with heart failure. Only when the results of these and other studies are known will it be possible to come to firm conclusions about whether patients with heart failure and coronary disease should be treated differently from other patients with heart failure due to left ventricular systolic dysfunction.

Changes in magnetic resonance imaging and sex behavior after 6-OHDA injection in the medial preoptic area.

Magnetic resonance imaging (MRI) of the brains of male rats was done before and after destroying the catecholamine (CA) fibers by local application of 6-hydroxydopamine (6-OHDA) in the medial preoptic area (mPOA). The male sexual behavior was also assessed before and after injection of this toxic drug. The administration of 6-OHDA (8 microg) resulted in highly variable lesions, as shown by MRI and confirmed by histological examination. A hyperintense area was visible either on one or on both sides, about 1-3 h after the administration of the drug. Postmortem histofluorescence showed destruction of CA fibers in the mPOA on those sides that showed hyperintense areas in the MRI. No CA fiber destruction was seen in those rats that had shown no change in MRI after 6-OHDA injection. There was a transient reduction in sex drive score in all the 6-OHDA-treated rats. The present findings point out a correlation between the MRI changes and CA fiber destruction, whereas the transient reduction in the sexual behavior was not related to these changes. It is suggested that some biochemical events related to 6-OHDA destruction of CA fibers may have been responsible for the hyperintensity seen in the MRI.

Evidence of oxidative stress in mdx mouse muscle: studies of the pre-necrotic state.

Considerable evidence indicates that free radical injury may underlie the pathologic changes in muscular dystrophies from mammalian and avian species. We have investigated the role of oxidative injury in muscle necrosis in mice with a muscular dystrophy due to a defect in the dystrophin gene (the mdx strain). In order to avoid secondary consequences of muscle necrosis, all experiments were done on muscle prior to the onset of the degenerative process (i.e. during the 'pre-necrotic' phase) which lasted up to 20 days of age in the muscles examined. In pre-necrotic mdx muscle, there was an induction of expression of genes encoding antioxidant enzymes, indicative of a cellular response to oxidative stress. In addition, the levels of lipid peroxidation were greater in mdx muscle than in the control. Since the free radical nitric oxide (NO*) has been shown to mediate oxidative injury in various disease states, and because dystrophin has been shown to form a complex with the enzyme nitric oxide synthase, we examined pre-necrotic mdx muscle for evidence of NO*-mediated injury by measuring cellular nitrotyrosine formation. By both immunohistochemical and electrochemical analyses, no evidence of increased nitrotyrosine levels in mdx muscle was detected. Therefore, although no relationship with NO*-mediated toxicity was found, we found evidence of increased oxidative stress preceding the onset of muscle cell death in dystrophin-deficient mice. These results lend support to the hypothesis that free radical-mediated injury may contribute to the pathogenesis of muscular dystrophies.

Role of medial preoptic area beta adrenoceptors in the regulation of sleep-wakefulness.

The role of the medial preoptic area (mPOA) beta adrenergic receptors in the regulation of sleep-wakefulness (S-W) was investigated in this study. S-W was assessed on the basis of polygraphic recording of EEG, EMG and EOG in free moving rats. Intracerebral microinjection of beta agonist, isoproterenol, into the mPOA produced arousal. The study was also conducted on another set of rats in which noradrenergic (NE) innervation to the mPOA was destroyed by injecting 6-hydroxydopamine into the ventral noradrenergic bundle, in the brain stem. Local application of isoproterenol, into the mPOA, in these animals, did not produce any significant change in S-W. Thus, the increase in awake period obtained on isoproterenol administration was the result of its action on the presynaptic NE terminals. Possible involvement of other responses in the isoproterenol induced increase in wakefulness, is discussed.

Asian Indians, coronary artery disease, and physical exercise.

OBJECTIVE: To evaluate the relation of physical activity to different clinical and biochemical risk factors for coronary artery disease among people from different ethnic groups with angiographically proven coronary artery disease. SUBJECTS: British Asians, Indian Asians, and white people suffering from coronary artery disease, and their respective controls. INTERVENTIONS: History, physical examination, coronary angiography (at baseline), laboratory investigations. MAIN OUTCOME MEASURES: Relation of physical activity level to serum insulin, glucose, cholesterol, triglycerides, and high density lipoproteins, systolic and diastolic blood pressures, and body mass index in patients and controls. RESULTS: 391 male patients were studied, of whom 260 (66.5%) were classified as sedentary. Mean serum insulin at 0, 1, and 2 hours after 75 g oral glucose was higher among the sedentary population (17.1 v 11.6, 88.2 v 62.1, and 57.9 v 36.2 microU/ml, respectively (all p < 0.0001). Mean body mass index was also higher among the sedentary population (25.53 v 23.95, p < 0.0001), as were mean serum triglycerides (1.85 v 1.60 mmol/l, p < 0.01) and systolic and diastolic blood pressures (133.9 v 129.4, p < 0.05, and 81.1 v 79.0, p < 0.01). There was no difference in the mean serum cholesterol and high density lipoprotein between the two groups. British Asians were the most sedentary and Indian Asians the most physically active. CONCLUSIONS: There are marked differences in the level of physical activity among the various ethnic groups in the United Kingdom. In each ethnic group, physical activity reduced mean serum insulin, body mass index, and serum triglycerides and had a favourable effect on systolic and diastolic blood pressures. Promotion of physical activity could be of value for the Asian community in the United Kingdom.

Myoblast-mediated expression of colony stimulating factor-1 (CSF-1) in the cytokine-deficient op/op mouse.

The osteopetrotic (op/op) mouse lacks colony stimulating factor-1 (CSF-1) due to an inactivating mutation in the CSF-1 gene. Intramuscular transplantation of engineered myoblasts was used to introduce CSF-1 into the circulation of op/op mice. The CSF-1 cDNA was introduced into C2C12 mouse myoblasts in culture using retroviral mediated gene transfer. Upon transplantation into the skeletal muscle of mutant mice, physiological levels of the cytokine were achieved systemically and elicited a biological response: circulating monocytes were induced. Howvever, both circulating CSF-1 levels and the induction of monocytes were transient. Analysis of the site of cell transplantation revealed local changes that may account for the transience of serum cytokine levels. Macrophage markers were induced in muscle tissue implanted with CSF-1 expressing myoblasts: c-fms, the CSF-1 receptor as well as the lineage-restricted antigen F4/80. We propose that in addition to CSF-1 clearance by Kupffer cells of the liver, macrophages that accumulated at the site of cell transplantation bound the CSF-1 produced by the muscle cell transplants, precluding the sustained release of this cytokine into the systemic circulation. Our studies also revealed that damage to muscle caused during cell transplantation or by freeze injury resulted in the accumulation of macrophages in op/op mouse muscle tissue. Indeed, op/op mice were fully capable of regenerating injured muscle suggesting the presence of as yet unidentified CSF-1-independent factors capable of generating macrophages that presumably participate in tissue remodeling in this cytokine-deficient mouse.

Coronary heart disease risks in Asian Indians.

An increased prevalence of coronary heart disease in Asian Indian both from the native country and the immigrant population has been known for some time. With around 15,000,000 Asian Indians living outside India including 1,500,000 in the UK and 1,000,000 in the US, various pathogenic factors have attracted great interest in the recent past. Prevention strategies have been recommended based on these findings. Insulin resistance, central obesity and lipid abnormalities such as high triglyceride levels, low HDL levels and high lipoprotein(a) levels have been documented. This predisposition to accelerated atherosclerosis is genetically determined but is being enhanced by change in lifestyle, or 'westernization'. An increased prevalence of coronary heart disease because of these changes in lifestyle is seen in India itself, where differences are found between urban and rural populations. This tendency seems to be noticed early in life, and hence the need for early prevention strategies are discussed.

Anchorage-dependent control of muscle-specific gene expression in C2C12 mouse myoblasts.

Our previous studies have demonstrated that expression of growth-associated genes is regulated by the adhesive state of the cell. To understand the role of cell adhesion in regulating the switch from growth to differentiation, we are studying the differentiation of mouse myoblasts into multinucleated contractile myotubes. In this report, we describe a novel means of culturing C2C12 myoblasts that permits an analysis of the role of cell adhesion in regulating the sequential induction of muscle-specific genes that control myogenesis. Suspension of an asynchronous, proliferating population of myoblasts in a viscous gel of methylcellulose dissolved in medium containing 20% serum induces growth arrest in G0 phase of the cell cycle without a concomitant induction of muscle-specific genes. Reattachment to a solid substratum in 20% serum, 0.5 nM bFGF, or 10 nM IGF-1 rapidly activates entry of the quiescent cells into G1 followed by a synchronous progression of the cell population through into S phase. bFGF or IGF-1 added separately facilitate only one passage through the cell cycle, whereas 20% serum or the two growth factors added together support multiple cell divisions. Adhesion of suspended cells in DMEM alone or with 3 nM IGF-1 induces myogenesis as evidenced by the synthesis of myogenin and myosin heavy chain (MHC) proteins followed by fusion into myotubes. bFGF completely inhibits this differentiation process even in the presence of myogenic doses of IGF-1. Addition of 3 nM IGF-1 to quiescent myoblasts maintained in suspension culture in serum-free conditions does not induce myogenin or MHC expression. Thus, adhesion is a requirement for the induction of muscle gene expression in mouse myoblasts. The development of a muscle cell culture environment in which proliferating myoblasts can be growth arrested in G0 without activating muscle-specific gene expression provides a means of analyzing the synchronous activation of either the myogenic or growth programs and how adhesion affects each process, respectively.

Tetracycline-regulated gene expression following direct gene transfer into mouse skeletal muscle.

For most experimental and therapeutic applications of gene transfer, regulation of the timing and level of gene expression is preferable to constitutive gene expression. Among the systems that have been developed for pharmacologically controlled gene expression in mammalian cells, the bacterial tetracycline (tet)-responsive system has the advantage that it is dependent on a drug (tet) that is both highly specific and non-toxic. The tet-responsive system has been previously used to modulate expression of cell cycle regulatory proteins in cultured cells, reporter genes in plants and transgenic mice and reporter genes directly injected into the heart. Here we show that orally or parenterally administered tet regulates expression of tet-responsive plasmids injected directly into mouse skeletal muscle. Reporter gene expression was suppressed by two orders of magnitude in the presence of tet, and that suppression was reversed when tet was withdrawn. These data show that skeletal muscle offers an accessible and well characterized target tissue for tet-controlled expression of genes in vivo, suggesting applications to developmental studies and gene therapy.

Are Asian coronary arteries smaller than Caucasian? A study on angiographic coronary artery size estimation during life.

Asian immigrants to the UK have a higher mortality from coronary artery disease (CAD) than native Caucasians. There is a clinical impression that Asians have smaller coronary arteries than Caucasians. In the present study, consecutive series of 72 male Caucasian and 70 male Asian patients undergoing diagnostic coronary angiography were recruited. Measurements of proximal disease-free segments of the three major coronary arteries were made using the catheter tip as the calibrating object. Electronic callipers were used for all measurements. Total coronary artery diameter was derived by adding the diameters of right, left anterior descending and circumflex arteries. Asians had significantly smaller total vessel diameter compared to Caucasians. They also had smaller body surface areas. This observation has important therapeutic implications regarding coronary intervention in this ethnic group already suffering excess mortality from CAD.

Insulin resistance, high prevalence of diabetes, and cardiovascular risk in immigrant Asians. Genetic or environmental effect?

OBJECTIVES: To compare the prevalence of diabetes, hyperinsulinaemia, and associated metabolic abnormalities in immigrant Asians, Asians in India, and native white British men. DESIGN: Case control study. SETTING: Wythenshawe Hospital, Manchester, United Kingdom, and Maulana Azad Medical School, New Delhi, India. SUBJECTS: Men with angiographically proved coronary artery disease; 83 British Asians, 87 white men, and 30 Indian Asians with age matched controls. INTERVENTIONS: Fasting lipid concentrations, serum glucose, and total insulin concentrations were measured in the fasting state and one and two hours after a 75 g glucose load by mouth. All subjects had a physical examination by the same observer. RESULTS: Asians in the United Kingdom and in India had a higher prevalence of diabetes and impaired glucose tolerance than the white British men. Patients in all three ethnic groups had higher total insulin concentrations than their controls in the fasting state and after the glucose load. British Asian and Indian Asian patients and controls had higher total insulin concentrations than the white men in the fasting state and after the glucose load. Total insulin concentrations were similar in British and Indian Asians, though fasting concentrations were higher in British Asians than Indian Asians. White men had similar cholesterol, lower triglyceride, and higher high density lipoprotein cholesterol concentrations than Asians in the United Kingdom and in India. British Asian patients had higher cholesterol concentrations and British Asian controls had higher triglyceride concentrations than the Indian Asian groups. Asian patients and controls were more active. British and Indian Asian patients had higher waist to hip ratios than controls. The waist to hip ratio was positively correlated with insulin and triglyceride concentrations and negatively correlated with the high density lipoprotein cholesterol concentration. Fasting insulin and high density lipoprotein concentrations were independent predictors of coronary artery disease in white men, whereas in British Asians the waist to hip ratio was the strongest independent predictor. In Indian Asians the waist to hip ratio and high density lipoprotein concentration were independent predictors of coronary artery disease. CONCLUSIONS: Central obesity in the subgroups of Asians studied showed a close association with hyperinsulinaemia and the risk of coronary artery disease. A predisposition to insulin resistance and its metabolic abnormalities in this group of Asians seems to be genetically determined, environmental changes after migration having only a small additional effect.