Temporal drivers of tryptophan-like fluorescent dissolved organic matter along a river continuum.

Tryptophan-like fluorescence (TLF) is used to indicate anthropogenic inputs of dissolved organic matter (DOM), typically from wastewater, in rivers. We hypothesised that other sources of DOM, such as groundwater and planktonic microbial biomass can also be important drivers of riverine TLF dynamics. We sampled 19 contrasting sites of the River Thames, UK, and its tributaries. Multivariate mixed linear models were developed for each site using 15 months of weekly water quality observations and with predictor variables selected according to the statistical significance of their linear relationship with TLF following a stepwise procedure. The variables considered for inclusion in the models were potassium (wastewater indicator), nitrate (groundwater indicator), chlorophyll-a (phytoplankton biomass), and Total bacterial Cells Counts (TCC) by flow cytometry. The wastewater indicator was included in the model of TLF at 89 % of sites. Groundwater was included in 53 % of models, particularly those with higher baseflow indices (0.50-0.86). At these sites, groundwater acted as a negative control on TLF, diluting other potential sources. Additionally, TCC was included positively in the models of six (32 %) sites. The models on the Thames itself using TCC were more rural sites with lower sewage inputs. Phytoplankton biomass (Chlorophyll-a) was only used in two (11 %) site models, despite the seasonal phytoplankton blooms. It is also notable that, the wastewater indicator did not always have the strongest evidence for inclusion in the models. For example, there was stronger evidence for the inclusion of groundwater and TCC than wastewater in 32 % and 5 % of catchments, respectively. Our study underscores the complex interplay of wastewater, groundwater, and planktonic microbes, driving riverine TLF dynamics, with their influence determined by site characteristics.

A survey of topsoil arsenic and mercury concentrations across France.

Even at low concentrations, the presence of arsenic and mercury in soils can lead to ecological and health impacts. The recent European-wide LUCAS Topsoil Survey found that the arsenic concentration of a large proportion of French soils exceeded a threshold which indicated that further investigation was required. A much smaller proportion of soils exceeded the corresponding threshold for mercury but the impacts of mining and industrial activities on mercury concentrations are not well understood. We use samples from the French national soil monitoring network (RMQS: Réseau de Mesures de la Qualité des Sols) to explore the variation of topsoil arsenic and mercury concentrations across mainland France at a finer spatial resolution than was reported by LUCAS Topsoil. We use geostatistical methods to map the expected concentrations of these elements in the topsoil and the probabilities that the legislative thresholds are exceeded. We find that, with the exception of some areas where the geogenic concentrations and soil adsorption capacities are very low, arsenic concentrations are generally larger than the threshold which indicates that further assessment of the area is required. The lower of two other guideline values indicating risks to ecology or health is exceeded in fewer than 5% of RMQS samples. These exceedances occur in localised hot-spots primarily associated with mining and mineralization. The probabilities of mercury concentrations exceeding the further assessment threshold value are everywhere less than 0.01 and none of the RMQS samples exceed either of the ecological and health risk thresholds. However, there are some regions with elevated concentrations which can be related to volcanic material, natural mineralizations and industrial contamination. These regions are more diffuse than the hot-spots of arsenic reflecting the greater volatility of mercury and therefore the greater ease with which it can be transported and redeposited. The maps provide a baseline against which future phases of the RMQS can be compared and highlight regions where the threat of soil contamination and its impacts should be more closely monitored.

Are sanitation interventions a threat to drinking water supplies in rural India? An application of tryptophan-like fluorescence.

Open defecation is practised by over 600 million people in India and there is a strong political drive to eliminate this through the provision of on-site sanitation in rural areas. However, there are concerns that the subsequent leaching of excreta from subsurface storage could be adversely impacting underlying groundwater resources upon which rural populations are almost completely dependent for domestic water supply. We investigated this link in four villages undergoing sanitary interventions in Bihar State, India. A total of 150 supplies were sampled for thermotolerant (faecal) coliforms (TTC) and tryptophan-like fluorescence (TLF): an emerging real-time indicator of faecal contamination. Sanitary risk inspections were also performed at all sites, including whether a supply was located within 10 m of a toilet, the recommended minimum separation. Overall, 18% of water supplies contained TTCs, 91% of which were located within 10 m of a toilet, 58% had TLF above detection limit, and sanitary risk scores were high. Statistical analysis demonstrated TLF was an effective indicator of TTC presence-absence, with a possibility of TTCs only where TLF exceeded 0.4 µg/L dissolved tryptophan. Analysis also indicated proximity to a toilet was the only significant sanitary risk factor predicting TTC presence-absence and the most significant predictor of TLF. Faecal contamination was considered a result of individual water supply vulnerability rather than indicative of widespread leaching into the aquifer. Therefore, increasing faecal contamination of groundwater-derived potable supplies is inevitable across the country as uptake of on-site sanitation intensifies. Communities need to be aware of this link and implement suitable decentralised low-cost treatment of water prior to consumption and improve the construction and protection of new supplies.

In-situ tryptophan-like fluorescence: A real-time indicator of faecal contamination in drinking water supplies.

Enteric pathogens are typically inferred from the presence of surrogate indicator organisms such as thermotolerant (faecal) coliforms (TTCs). The analysis of TTCs requires time-consuming incubation in suitable laboratories, which can limit sampling resolution, particularly during critical pollution events. Here, we demonstrate the use of in-situ fluorimeters targeting tryptophan-like compounds as a rapid, reagentless indicator of TTCs in groundwater-derived potable water supplies in Africa. A range of other common indicators of TTCs were also determined including nitrate, turbidity, and sanitary risk survey scores. Sampling was conducted during both the dry and wet seasons to investigate seasonality. Tryptophan-like fluorescence was the most effective predictor of both presence/absence and number of TTCs during both seasons. Seasonal changes in tryptophan-like fluorescence in deeper supplies suggest it is transported more efficiently through the aquifer than TTCs. Moreover, the perennial elevated concentrations in some wells suggest it is more resilient than TTCs in groundwater. Therefore tryptophan-like fluorescence could also be a better indicator of some smaller, more easily transported, and long-lived, pathogenic enteric viruses. These sensors have the potential to be included in real-time pollution alert systems for drinking water supplies throughout the world, as well as for mapping enteric pathogen risks in developing regions.

Model-based drug development: a rational approach to efficiently accelerate drug development.

The pharmaceutical industry continues to face significant challenges. Very few compounds that enter development reach the marketplace, and the investment required for each success can surpass $1.8 billion. Despite attempts to improve efficiency and increase productivity, total investment continues to rise whereas the output of new medicines declines. With costs increasing exponentially through each development phase, it is failure in phase II and phase III that is most wasteful. In today's development paradigm, late-stage failure is principally a result of insufficient efficacy. This is manifested as either a failure to differentiate sufficiently from placebo (shown for both novel and precedented mechanisms) or a failure to demonstrate sufficient differentiation from existing compounds. Set in this context, this article will discuss the role model-based drug development (MBDD) approaches can and do play in accelerating and optimizing compound development strategies through a series of illustrative examples.

Spatial distribution of Lindane concentration in topsoil across France.

Lindane [γ-hexachlorocyclohexane (γ-HCH)] is an organochlorine pesticide with toxic effects on humans. It is bioaccumulative and can remain in soils for long periods, and although its use for crop spraying was banned in France in 1998, it is possible that residues from before this time remain in the soil. The RMQS soil monitoring network consists of soil samples from 2200 sites on a 16 km regular grid across France, collected between 2002 and 2009. We use 726 measurements of the Lindane concentration in these samples to (i) investigate the main explanatory factors for its spatial distribution across France, and (ii) map this distribution. Geostatistics provides an appropriate framework to analyze our spatial dataset, though two issues regarding the data are worth special consideration: first, the harmonization of two subsets of the data (which were analyzed using different measurement processes), and second, the large proportion of data from one of these subsets that fell below a limit of quantification. We deal with these issues using recent methodological developments in geostatistics. Results demonstrate the importance of land use and rainfall for explaining part of the variability of Lindane across France: land use due to the past direct input of Lindane on cropland and its subsequent persistence in the soil, and rainfall due to the re-deposition of volatilized Lindane. Maps show the concentrations to be generally largest in the north and northwest of France, areas of more intensive agricultural land. We also compare levels to some contamination thresholds taken from the literature, and present maps showing the probability of Lindane concentrations exceeding these thresholds across France. These maps could be used as guidelines for deciding which areas require further sampling before some possible remediation strategy could be applied.

Spatial sampling to detect an invasive pathogen outside of an eradication zone.

Invasive pathogens are known to cause major damage to the environments they invade. Effective control of such invasive pathogens depends on early detection. In this paper we focus on sampling with the aim of detecting an invasive pathogen. To that end, we introduce the concept of optimized spatial sampling, using spatial simulated annealing, to plant pathology. It has been mathematically proven (15) that this optimization method converges to the optimum allocation of sampling points that give the largest detection probability. We show the benefits of the method to plant pathology by (i) first illustrating that optimized spatial sampling can easily be applied for disease detection, and then we show that (ii) combining it with a spatially explicit epidemic model, we can develop optimum sample schemes, i.e., optimum locations to sample that maximize the probability of detecting an invasive pathogen. This method is then used as baseline against which other sampling methods can be tested for their accuracy. For the specific example case of this paper, we test (i) random sampling, (ii) stratified sampling as well as (iii) sampling based on the output of the simulation model (using the most frequently infected hosts as sample points), and (iv) sampling the hosts closest to the outbreak point.

Factors affecting return of symptoms 1 year after treatment in a 62-week controlled study of fluoxetine in major depression.

BACKGROUND: In spite of impressive results in acute studies, the long-term treatment of major depression remains problematic. To explore the return of depressive symptoms and their interaction with social factors on long-term outcome, we assessed 55 patients whose depression had been treated during a 62-week, fluoxetine maintenance study, 1 year after the study's termination. METHOD: During the year following the study termination, patients were free to select treatment options. Assessments at the 1-year follow-up included measures of depressive symptoms (using the Hamilton Rating Scale for Depression [HAM-D]), social and marital impairment (using the Weissman Social Adjustment Scale [SAS]), personal stressors (using the Holmes Social Readjustment Rating Scale), and history of treatment during the past year. RESULTS: At the time of the naturalistic follow-up, 53% of patients sustained their improvement in mood. Factors associated with return of depressive symptoms included personal stresses, marital maladjustment, personal decision to discontinue antidepressants, and medication failure. Psychosocial variables were associated with poor outcome in over 90% of impaired subjects. Development of subsyndromal symptoms during the 50-week double-blind phase was predictive of poorer outcome at the long-term follow-up. CONCLUSION: The study demonstrates that no matter how effective initial pharmacologic therapy may be, without ongoing clinical monitoring and support, particularly in dealing with issues such as marriage and handling significant life stresses, and compliance with medications, it will not be successful in the long-term treatment for a significant portion of patients with depression.

Screening of a HUVEC cDNA library with transplant-associated coronary artery disease sera identifies RPL7 as a candidate autoantigen associated with this disease.

A HUVEC cDNA library was screened with sera from two patients who had developed transplant-associated coronary artery disease (TxCAD) following cardiac transplantation. A total of six positive clones were isolated from a primary screen of 40 000 genes. Subsequent DNA sequence analysis identified these to be lysyl tRNA synthetase, ribosomal protein L7, ribosomal protein L9, beta transducin and TANK. Another gene whose product could not be identified showed homology to a human cDNA clone (DKFZp566M063) derived from fetal kidney. Full-length constructs of selected genes were expressed as his-tag recombinant fusion proteins and used to screen a wider patient base by ELISA to determine prevalence and association with TxCAD. Of these ribosomal protein L7 showed the highest prevalence (55.6%) with TxCAD sera compared to 10% non-CAD.

Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with reduced left ventricular function: a Danish investigations of arrhythmia and mortality on dofetilide (diamond) substudy.

BACKGROUND: In patients with left ventricular dysfunction, atrial fibrillation and flutter (AF and AFl, respectively) are common arrhythmias associated with increased morbidity and mortality. The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm, which might reduce mortality and hospitalizations. METHODS AND RESULTS: In the Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies, 506 patients were in AF-AFl at baseline. Over the course of study, cardioversion occurred in 148 (59%) dofetilide- and 86 (34%) placebo-treated patients. In these patients, the probability of maintaining sinus rhythm for 1 year was 79% with dofetilide versus 42% with placebo (P<0.001). Dofetilide had no effect on all-cause mortality, but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality (risk ratio [RR], 0.44; 95% CI, 0.30 to 0.64; P<0.0001). In addition, dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause (RR, 0.70; 95% CI, 0.56 to 0.89; P

TGF-beta3 in the treatment of pressure ulcers: a preliminary report.

OBJECTIVE: To determine the safety, tolerability, and efficacy of TGF-beta3 in the treatment of chronic, nonhealing pressure ulcers. DESIGN: A subset analysis of data from a randomized, blind, parallel, placebo-controlled trial involving 270 patients. SETTING: University of Michigan Wound Care Center. PATIENTS: A total of 14 patients (6 women and 8 men aged > or = 18 years) with pressure ulcers were randomly assigned to 1 of 3 groups to receive once daily topical application of recombinant TGF-beta3 or placebo gel for a period of no more than 16 weeks. Group 1 (n=4) received 1.0 microg/cm2 of TGF-beta3, Group 2 (n=5) received 2.5 microg/cm2 of TGF-beta3, and Group 3 (n=5) received placebo gel. All subjects received standardized wound care as well. Weekly evaluations were performed for efficacy, determined by relative wound surface areas and volumes, and were compared with initial baseline values and safety parameters. MAIN OUTCOME MEASURE: Reduction in pressure ulcer area and volume. MAIN RESULTS: Group 2 had a significantly increased rate of wound healing at the fourth visit (P<.05). No significant difference was observed in the healing rate among the groups at the termination of the study. Treatment with TGF-beta3 was well tolerated and there were no significant adverse reactions. CONCLUSION: The findings of this study indicate that the topical application of TGF-beta3 is safe and useful in the treatment of pressure ulcers and is most effective at the earliest stages of therapy.

Analysis of the physician variable in pain management.

BACKGROUND: The role of physician variability in pain management is unknown. OBJECTIVE: To assess the role of physician variability in the management of pain and provide quantitative data regarding the status of pain management in Michigan. DESIGN: A multi-item mail survey was used to determine the physician's perceived knowledge of pain management modalities, goals, satisfaction, and confidence with pain treatment. Participants. The focus of this report was a group of 368 licensed Michigan physicians who provide clinical care. RESULTS: Overall, 30% of the study group reported no formal education in pain management, although younger physicians reported more education (correlation coefficient = -0.252, P <.001). The physicians reported greater confidence in their knowledge of meperidine than other Schedule II opioids (P <.001 ). In regards to the opinion that prescribing strong opioids would attract a medical review, the physician responses ranged from 1 (strongly disagree) to 5 (strongly agree). The median score for this scale was 4, accounting for 46% of the responses. The study group expressed less satisfaction with their treatment of chronic pain as well as lower goals for relief (mean: 3.8; 95% confidence interval: 3.7-3.9). CONCLUSIONS: Lower expectations for relief and less satisfaction in its management may contribute to the undertreatment of chronic pain. Perceptions of regulatory scrutiny may contribute to suboptimal pain management. These preliminary data highlight physician variability in pain decision making while providing insights into educational needs.

Osteomyelitis related to pressure ulcers: the cost of neglect.

Twelve patients with documented chronic osteomyelitis of the pelvis resulting from truncal pressure ulcers were examined retrospectively to identify the cost of treatment for this significant health care problem. The retrospective review of each case spanned an 18-month period--6 months prior to the initial positive bone biopsy to 1 year following bone biopsy. The financial charges associated with treatment of osteomyelitis were identified using the University of Michigan Health System's databases for hospital charges, professional charges, and pharmacy charges. Prior treatment of these patients included surgical debridement of the pressure ulcer, pelvic bone biopsy, and culture-specific antibiotic therapy. The total charges for this group of 12 patients was $715,204, or an average charge of $59,600 per patient. Each patient was hospitalized, with hospitalization charges of $587,212, or an average of $48,934 per patient. Pharmacy charges for culture-specific antibiotics totaled $85,217 for the 12 patients. Six of 8 flap repairs achieved successful surgical closure of the pressure ulcer (75%) postantibiotic therapy. Surgery charges are not included in the totals.

Role of platelet-derived growth factor as an adjunct to surgery in the management of pressure ulcers.

Management options for pressure ulcers include local wound care, surgical repair, and, more recently, topical application of platelet-derived growth factor (PDGF). PDGF is a glycoprotein that is mitogenic for mesenchymal cells and has been studied extensively for applicability in promoting the healing of chronic human wounds. Using data obtained from a multicenter clinical trial for the treatment of full-thickness pressure ulcers, a subset analysis was performed to investigate the outcome of salvage surgery for pressure ulcers, after incomplete closure occurred with the topical use of either recombinant human PDGF-BB (rhPDGF-BB) or placebo gel. At the University of Michigan Wound Care Center, subset data from a randomized, double-blind, placebo-controlled, parallel group clinical trial were reviewed to compare the effects of three concentrations of rhPDGF-BB on full-thickness pressure ulcers of the trunk with those of the placebo. Twenty-eight patients were enrolled and 27 completed the trial. An intent-to-treat analysis was used to evaluate data. If the ulcer did not heal by the end of the 16-week trial period, the surgeon, still blinded to the treatment group, offered salvage surgical repair of the pressure ulcer. Eleven patients underwent salvage surgical repair using myocutaneous flaps, primary closure, or skin grafts. Of three patients who received placebo followed by surgery, none progressed to full healing within 1 year. Of 12 patients in the treatment group who received rhPDGF-BB and salvage surgery, 11 (92 percent) ultimately healed the ulcers within 1 year after the start of the clinical trial. These findings suggest that treatment with rhPDGF-BB before surgery enhances the ability to achieve a closed wound over surgery alone. It must yet be determined to what degree rhPDGF-BB contributed to the excellent results seen in the rhPDGF-BB/surgery group. It is possible that rhPDGF-BB "primes" the local wound milieu to make it more responsive to complete closure following surgical treatment.

Autonomic dysfunction is related to impaired pancreatic beta cell function in patients with coronary artery disease.

OBJECTIVE: To assess the role of beta cell failure in the development of autonomic dysfunction in patients with coronary artery disease. DESIGN: Autonomic function was measured by standard clinical methods and by heart rate variability in 24 type II diabetic and 24 non-diabetic subjects with coronary artery disease. Quantitative estimates of pancreatic beta cell function (%beta) and insulin resistance were made from basal plasma glucose and insulin concentrations using a computer solved model. Fasting proinsulin levels provided an independent measure of beta cell function. RESULTS: The circadian rhythm of sympathovagal balance (ratio of low to high frequency spectral components of heart rate variability) was significantly attenuated in patients with below median (%beta

Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial.

BACKGROUND: Arrhythmias cause much morbidity and mortality after myocardial infarction, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide, a new class III agent, was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infarction. METHODS: In 37 Danish coronary-care units, 1510 patients with severe left-ventricular dysfunction (wall motion index < or = 1.2, corresponding to ejection fraction < or = 0.35) were enrolled in a randomised, double-blind study comparing dofetilide (n=749) with placebo (n=761). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths. Analyses were by intention to treat. FINDINGS: No significant differences were found between the dofetilide and placebo groups in all-cause mortality (230 [31%] vs 243 [32%]), cardiac mortality (191 [26%] vs 212 [28%]), or total arrhythmic deaths (129 [17%] vs 140 [18%]). Atrial fibrillation or flutter was present in 8% of the patients at study entry. In these patients, dofetilide was significantly better than placebo at restoring sinus rhythm (25 of 59 vs seven of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group. INTERPRETATION: In patients with severe left-ventricular dysfunction and recent myocardial infarction, treatment with dofetilide did not affect all-cause mortality, cardiac mortality, or total arrhythmic deaths. Dofetilide was effective in treating atrial fibrillation or flutter in this population.

Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.

BACKGROUND: Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization. Sinus rhythm may be maintained with antiarrhythmic drugs, but some of these drugs increase the risk of death. METHODS: We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals. We randomly assigned 762 patients to receive dofetilide, a novel class III antiarrhythmic agent, and 756 to receive placebo in a double-blind study. Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment. The primary end point was death from any cause. RESULTS: During a median follow-up of 18 months, 311 patients in the dofetilide group (41 percent) and 317 patients in the placebo group (42 percent) died (hazard ratio, 0.95; 95 percent confidence interval, 0.81 to 1.11). Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure (risk ratio, 0.75; 95 percent confidence interval, 0.63 to 0.89). Dofetilide was effective in converting atrial fibrillation to sinus rhythm. After one month, 22 of 190 patients with atrial fibrillation at base line (12 percent) had sinus rhythm restored with dofetilide, as compared with only 3 of 201 patients (1 percent) given placebo. Once sinus rhythm was restored, dofetilide was significantly more effective than placebo in maintaining sinus rhythm (hazard ratio for the recurrence of atrial fibrillation, 0.35; 95 percent confidence interval, 0.22 to 0.57; P<0.001). There were 25 cases of torsade de pointes in the dofetilide group (3.3 percent) as compared with none in the placebo group. CONCLUSIONS: In patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality.

Attenuation or absence of circadian and seasonal rhythms of acute myocardial infarction.

OBJECTIVES: To examine the circadian, seasonal, and weekly rhythms of acute myocardial infarction, and to identify subgroups in whom the rhythms are attenuated or absent to provide further information about the mechanisms of the rhythms and the processes responsible for triggering plaque events. DESIGN AND SETTING: Prospective, observational study in a general hospital. PATIENTS AND METHODS: 1225 consecutive patients admitted to a coronary care unit with acute myocardial infarction were studied. Admission rates were calculated according to the hour of the day (circadian rhythm), day of the week (weekly rhythm), and month of year (seasonal rhythm). The data were analysed for variations within the whole group and within subgroups. RESULTS: A weekly rhythm of acute myocardial infarction could not be demonstrated but there was a trend towards higher admission rates at the beginning of the week. However, the time of onset of symptoms showed significant circadian variation for the group as a whole, peaking in the morning (P = 0.006), against an otherwise fairly constant background rate. Subgroup analysis showed complete absence of the circadian rhythm in patients who were diabetic, South Asian, or taking beta blockers or aspirin on admission. Significant seasonal variation in admission rates was also demonstrated for the group as a whole with a winter peak and a summer trough (P = 0.009). Again, no seasonal rhythm could be demonstrated in patients who were diabetic, South Asian, or taking beta blockers or aspirin on admission. CONCLUSIONS: The absence of circadian and seasonal rhythms of acute myocardial infarction in almost identical subgroups suggests that common mechanisms are involved in driving these rhythms. The autonomic nervous system is a likely candidate because the rhythms were absent in patients taking beta blockers as well as in patients in whom derangement of autonomic function commonly occurs.

Comparison of case fatality in south Asian and white patients after acute myocardial infarction: observational study.

OBJECTIVE: To compare mortality in south Asian (Indian, Pakistani, and Bangladeshi) and white patients in the six months after hospital admission for acute myocardial infarction. DESIGN: Observational study. SETTING: District general hospital in east London. PATIENTS: 149 south Asian and 313 white patients aged < 65 years admitted to the coronary care unit with acute myocardial infarction from 1 December 1988 to 31 December 1992. MAIN OUTCOME MEASURE: All cause mortality in the first six months after myocardial infarction. RESULTS: The admission rate in the south Asians was estimated to be 2.04 times that in the white patients. Most aspects of treatment were similar in the two groups, except that a higher proportion of the south Asians received thrombolytic drugs (81.2% v 73.8%). After adjustment for age, sex, previous myocardial infarction, and treatment with thrombolysis or aspirin, or both, the south Asians had a poorer survival over the six months from myocardial infarction (hazard ratio 2.02 (95% confidence interval 1.14 to 3.56), P = 0.018), but a substantially higher proportion were diabetic (38% v 11%, P < 0.001), and additional adjustment for diabetes removed much of their excess risk (adjusted hazard ratio 1.26 (0.68 to 2.33), P = 0.47). CONCLUSION: South Asian patients had a higher risk of admission with myocardial infarction and a higher risk of death over the ensuing six months than the white patients. The higher case fatality among the south Asians, largely attributable to diabetes, may contribute to the increased risk of death from coronary heart disease in south Asians living in Britain.