On-the-Fly Fluorescence Lifetime Determination with Total Emission Detection in HPLC.

The entire fluorescence decay profile during HPLC elution has been directly measured on-the-fly in HPLC at higher sensitivity than in previous literature reports. The fluorescence is excited with the fourth harmonic (266 nm) of a pulsed Nd:YAG laser system and detected broadband with a photomultiplier tube and a digital storage oscilloscope. Detection limits in the range 1-10 ppb are found for several individual polycyclic aromatic hydrocarbons (PAHs) when the total time-integrated fluorescence is analyzed. The chromatograms of PAH mixtures containing 8-10 species were lifetime analyzed with a simple phase plane analysis, in which a single lifetime is determined from the fluorescence decay profile for each point on the chromatogram. The determination of lifetimes under coelution conditions is also illustrated and discussed.

Raised concentrations of glucose and adrenaline and increased in vivo platelet activation after myocardial infarction.

Plasma concentration of beta thromboglobulin was used as an index of in vivo platelet activation in 36 patients after acute myocardial infarction. Twelve patients had diabetes, seven had pulmonary oedema or cardiogenic shock (pump failure) or both, and 17 had uncomplicated infarcts. On the first day of admission, concentrations of beta thromboglobulin were higher in the patients with diabetes and those with pump failure than in those with uncomplicated infarcts. Concentrations of beta thromboglobulin in the non-diabetic patients were studied by multiple regression analysis and were significantly associated with plasma concentrations of adrenaline, pump failure, and glucose but not with noradrenaline or infarct size. When all subjects were considered together, glucose, adrenaline, and pump failure were associated with the beta thromboglobulin concentration but diabetes was without significant effect. Hyperglycaemia and raised plasma adrenaline concentration after myocardial infarction may activate platelets, and this could contribute to poor outcome in such patients.

Increased mean platelet volume after acute myocardial infarction relates to diabetes and to cardiac failure.

Mean platelet volume, platelet count and an estimate of platelet volume distribution were studied following acute myocardial infarction in 59 diabetics and 88 non-diabetics and were compared with values in 100 non-diabetic and 50 diabetic non-infarct subjects. In the non-diabetics mean platelet volume and platelet distribution width were similar in the non-infarcted patients and in the infarcted patients without severe cardiac failure. All diabetics with myocardial infarction had larger mean platelet volumes and platelet distribution width than the diabetic non-infarct controls. All myocardial infarction patients with severe cardiac failure had larger platelet volumes than patients with mild or no failure. Increased mean platelet volume may reflect either increased platelet activation or increased numbers of large, hyperaggregable platelets. Abnormalities of platelet function may contribute to the relatively poor prognosis of myocardial infarction in patients with diabetes.

The relationship of hospital admission and fatality from myocardial infarction to glycohaemoglobin levels.

We have performed a study to assess the relative contributions of increased hospital admission rates with acute myocardial infarction and increased hospital case fatality to the excess mortality of subjects with elevated levels of glycohaemoglobin from myocardial infarction. Glycohaemoglobin levels were estimated by isoelectric focussing in 397 subjects without known diabetes mellitus admitted with myocardial infarction and compared with a control population reconstructed from a community sample of 1084 subjects without known diabetes mellitus screened in general practice. In the case-control comparison, glycohaemoglobin levels above the 90th centile were associated with relative risks of 3.1 (95% confidence interval 1.4-6.8) for admission with myocardial infarction and 5.3 (95% confidence interval 2.1-13.4) for death in hospital. Elevated glycohaemoglobin on admission was a predictor of both death and cardiac pump failure among those admitted with myocardial infarction, as was the presence of known diabetes. In those over 40 years of age, the top 1% of the glycohaemoglobin distribution contribute 4.3% of admissions and 9.6% of hospital deaths with myocardial infarction.

Determinants of hospital admission and case fatality in diabetic patients with myocardial infarction.

We compare the clinical features and hospital outcomes in 83 diabetic patients admitted with acute myocardial infarction and 380 nondiabetic patients with levels of glycosylated hemoglobin (HbA1c) low enough to exclude undiagnosed diabetes. The hospital mortality was 42.2% in diabetic and 24.7% in nondiabetic patients, an odds ratio of 2.22 (CI 1.37-3.60, P less than .002). The excess mortality was due to cardiogenic shock and left ventricular failure (pump failure). There was no difference in peak levels of aspartate transaminase between the groups. Among the diabetic patients, the admission levels of plasma glucose and peak levels of aspartate transaminase were higher among those who developed pump failure or died, but there was no relationship between outcome and gender, disease duration, or treatment. Prior blood glucose control, as judged by levels of HbA1c, was not related to hospital outcome (P greater than .5). In a further study, the 83 diabetic patients were compared with 249 age- and sex-matched diabetic subjects without myocardial infarction for treatment, disease duration, and control. There was an increased risk of admission with myocardial infarction of 2.35 (CI 1.41-3.92, P less than .005) within the first 5 yr of diagnosis of diabetes. Infarct patients had significantly lower levels of HbA1c than control subjects (P less than .005), but treatment did not differ between groups. Neither incidence nor case fatality of myocardial infarction in diabetic patients is positively associated with cumulative glycemic exposure.

A within patient cross over trial of 4 insulin regimens in antibody-negative, C-peptide negative patients.

12 patients entered a within patient cross over trial of 4 insulin regimens:--twice daily semi-synthetic human soluble and insulin zinc suspension (Actrapid/Monotard HM), twice daily porcine soluble and insulin zinc suspension (Actrapid/Monotard), twice daily porcine soluble and isophane insulin (Velosulin/Insulatard), and thrice daily porcine soluble insulin (Actrapid) supplementing once daily bovine ultralente insulin (Ultratard). Each insulin regimen lasted 10 weeks, the order of allocation being determined on a random basis. Patients were encouraged to improve glycaemic control throughout the study by self adjustment of insulin dosage guided by standard algorithms. Metabolic control was assessed by capillary blood glucose series, M-values, HbA1c, and fasting lipids. No significant differences in M-values, mean HbA1c or fasting lipids were found at the end of any of the regimens. Patients achieved significantly (p less than 0.01) lower pre-lunch blood glucose on Velosulin/Insulatard than on any other regimen, but severe hypoglycaemic events were more common (p less than 0.05) on this regimen. A significant fall in HbA1c values from that at recruitment could be demonstrated only by analysing treatment periods in chronological order. Thus at the end of the second study period, mean HbA1c was significantly less than that at recruitment (p less than 0.01), but by the end of the 4 treatment periods of our study, had returned to levels similar to those at recruitment. Similar control is achieved on semi-synthetic human insulin as on other conventional regimens. Day-to-day variability of blood glucose, expressed as a standard deviation, is approximately twice the maximum difference between any 2 regimens at any time point.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in pulmonary venous pressure and albumin concentration during treatment of severe diabetic decompensation.

Pulmonary capillary wedge pressure (PCWP), serum albumin concentrations, and arterial oxygenation (PaO2) were monitored during crystalloid loading in 10 patients with severe decompensated diabetic states (SDDS). Rapid infusion of crystalloid induced marked rises in PCWP (median 6 mmHg, range 1-21 mmHg) and falls in albumin concentrations (median 5 g/l, range 0.8-15 g/l) over the first few hours of treatment. PaO2 was significantly related (r(s) = -0.25, p less than 0.05) to the calculated hydrostatic forces across the pulmonary capillary bed. However, hypoxaemia was found at initiation of therapy in 2 patients where calculated COP greatly exceeded PCWP. Hypoxaemia developing during crystalloid loading for SDDS may imply the formation of sub-clinical pulmonary oedema and the subsequent fluid replacement regimen should then be appropriately reviewed.

Hyperglycaemia following acute myocardial infarction: the contribution of undiagnosed diabetes.

We studied 397 patients admitted to hospital with acute myocardial infarction (AMI) to validate an admission level of haemoglobin A1c (HbA1c) diagnostic for previously unknown diabetes mellitus by assessing glucose tolerance after 3 months. In 38% of survivors clearly abnormal HbA1c level (greater than 7.8) was 100% sensitive and 99% specific for diabetes with fasting hyperglycaemia, although the sensitivity fell to 67% when three diabetic subjects without fasting hyperglycaemia were included. Admission hyperglycaemia (plasma glucose greater than or equal to 11 mmol/l) was present in 20% of patients with AMI, of whom only one in five had levels of HbA1c indicating prior diabetes. Glycosylated haemoglobin is a more sensitive and specific test for diabetes in patients with AMI than admission hyperglycaemia. Undiagnosed diabetes was found in 4.3% of subjects with AMI who contributed 9.6% of hospital mortality.

The extent of coronary artery disease in diabetic patients with myocardial infarction: an ECG study.

In 91 non-diabetics (age 63 +/- 12, mean +/- SD, years range 31-94 years) and 85 patients with known diabetes or clearly abnormal levels of HbA1c (age 66 +/- 10 years, range 36-87 years) electrocardiograms were analysed sequentially after acute myocardial infarction (AMI). There was no significant difference in infarct site between the two groups. Generalized ischaemic change without ST elevation was seen in 33% of diabetics and 22% of non-diabetics (p greater than 0.1). In patients with transmural AMI, cardiogenic shock (CGS) was significantly commoner in diabetics (relative risk 3.1, CL 1.2-8.1) but there was no difference in the frequency of reciprocal change between the two groups. In both diabetic and non-diabetic patients the development of cardiogenic shock was more frequently associated with the presence of reciprocal change, the difference reaching significance in the diabetic group (chi 2 = 4.4, p less than 0.05). Thus cardiogenic shock in both diabetic and non-diabetic patients with AMI may be associated with the presence of extensive coronary artery disease, but differences in the prevalence of extensive disease do not explain the predisposition of diabetic patients to CGS.

Determinants and importance of stress hyperglycaemia in non-diabetic patients with myocardial infarction.

Determinants of plasma glucose concentrations were studied in patients on admission to hospital with confirmed acute myocardial infarction but without previous glucose intolerance as evidenced by raised concentrations of glycosylated haemoglobin (HbAlc). Mortality in hospital increased significantly with increasing plasma concentrations of glucose in patients with both normal (p less than 0.0001, n = 311) and borderline (p less than 0.02, n = 70) concentrations of HbAlc. There was a weak relation between plasma glucose concentrations and infarct size as estimated by peak aspartate transaminase activity in both HbAlc groups (rs = 0.26, n = 101 and rs = 0.41, n = 35 respectively). A correlation was found between adrenaline and plasma glucose concentrations (r = 0.47, n = 27) and cortisol and plasma glucose concentrations (r = 0.75, n = 19), but the relation of plasma noradrenaline and plasma glucose suggested a threshold effect. Concentrations of adrenaline, but not those of noradrenaline or cortisol, correlated with infarct size as measured both by peak aspartate transaminase activity and cumulative release of creatine kinase MB isoenzyme. Multiple regression analysis showed that concentrations of cortisol, adrenaline, and noradrenaline (but not the concentration of HbAlc, infarct size, or age) are the main determinants of plasma glucose concentration measured in non-diabetic patients when admitted to hospital after acute myocardial infarction.

Prevalence and risks of hyperglycaemia and undiagnosed diabetes in patients with acute myocardial infarction.

Two studies were undertaken to assess the prevalence of undiagnosed diabetes mellitus in patients admitted with acute myocardial infarction (AMI), and the effect of diabetes mellitus and admission hyperglycaemia on outcome. In the retrospective study, admission levels of plasma glucose (APG) were higher (p less than 0.02) in patients dying from cardiogenic shock than in survivors, but they were not related to infarct size. In the prospective study APG was related (p less than 0.01) to concurrent levels of glycosylated haemoglobin (HbA1c), which were in turn related to outcome--the mortality rate was 23% for those with normal HbA1c (less than 7.5%), 33% for those with borderline abnormal HbA1c (7.5-8.5%), and 63% for those with clearly abnormal HbA1c (greater than 8.5%). Cardiogenic shock was commoner in the groups with higher HbA1c levels. In addition, admission hyperglycaemia was associated (p less than 0.01) with the incidence of cardiogenic shock even after correcting for the effects of HbA1c. All of the survivors from the clearly abnormal HbA1c group, but none of those from other groups, were diabetic at follow up, suggesting an overall prevalence of undiagnosed diabetes mellitus of 5.3%. The contribution of undiagnosed diabetes mellitus to total mortality following AMI seems at present to be underestimated.