Gender differences in the prevalence of metabolic syndrome in 50-year-old Swedish men and women with hypertension born in 1953.

To investigate potential gender differences in the role of hypertension as a risk factor for metabolic syndrome (MetS) we used a random population sample of 50-year-old men (n=595) and women (n=667; all born in 1953) who were examined in 2003-2004. Systolic (SBP) and diastolic (DBP) blood pressure values were dichotomized at ≥ 140 mm Hg and ≥ 90 mm Hg, respectively. MetS was defined using NCEP (National Cholesterol Education Programme) and IDF (International Diabetes Federation) criteria. MetS was more prevalent in men than in women (NCEP 16% versus 10%, P=0.003; IDF 26% versus 16%, P=0.000) and systolic hypertension was more common in men than in women (high SBP 24% versus 18%, P=0.003; high DBP 29% versus 24%, P=0.074). Women with high SBP had about a seven-fold increased NCEP risk compared with normotensive women (odds ratio (OR) 6.91, confidence interval (CI) 2.90-16.42), whereas high SBP in men was associated with about a three-fold increased NCEP risk (OR 2.72, CI 1.69-4.38). A similar pattern was observed for the IDF criterion of MetS. All interaction terms (sex × hypertension) were significant at P<0.01. At middle age, despite that fewer women had hypertension or MetS than men, hypertension carries a relatively greater risk for MetS in women than in men.

Factors associated with reaching 90 years of age: a study of men born in 1913 in Gothenburg, Sweden.

OBJECTIVES: Increasing numbers of people reach old age. We wanted to identify variables of importance for reaching 90 years old and determine how the predictive ability of these variables might change over time. SETTING AND SUBJECTS: All men in the city of Gothenburg born in 1913 on dates divisible by 3, which is on the 3rd, 6th, 9th etc., were included in the study. Thus, 973 men were invited, and 855 were examined in 1963 at age 50. Further examinations were made at age 54, 60 and 67. Anthropometric data, lifestyle and parental factors, blood pressure, lung function, X-ray of heart and lungs and maximum work performance were recorded. The area under the receiver operating characteristic curve was used to analyse the predictive capacity of a variable. RESULTS: A total of 111 men (13%) reached 90 years of age, men who reached 90 years were more likely at age 50 to be nonsmokers, consume less coffee, have higher socio-economic status and have low serum cholesterol levels than those who did not reach this age; however, at age 50 or 62, parents' survival was of no prognostic importance. Variables of greatest importance at higher ages were low blood pressure and measures related to good cardiorespiratory function. In multivariable analysis, including all examinations, being a nonsmoker, consuming small amounts of coffee, having high housing costs at age 50, good maximum working capacity and low serum cholesterol were related to a better chance of survival to age 90. CONCLUSIONS: Low levels of cardiovascular risk factors, high socio-economic status and good functional capacity, irrespective of parents' survival, characterize men destined to reach the age of 90.

Obesity, smoking and secular trends in cardiovascular risk factors in middle-aged women: data from population studies in Göteborg from 1980 to 2003.

BACKGROUND: To study the trends in cardiovascular risk factors in middle-aged city-dwelling Swedish women from 1980 to 2003. METHODS: Using cross-sectional population-based surveys, five random population samples of a total of 1915 women aged between 45 and 54 years, participating in the BEDA study in 1980, WHO MONICA studies in 1985, 1990 and 1995, and a study of 50-year-old women in 2003 were measured for the following parameters: anthropometry, serum cholesterol and triglyceride levels, smoking habits, blood pressure, physical activity and stress. RESULTS: Over almost 25 years, middle-aged women gained on average 4.4 kg in weight, with a net increase in body mass index (BMI) from 24.7 to 25.6 kg m⁻². The proportion of participants classified as obese (≥30 kg m⁻²) increased by 50% from 10.4% to 15.1%. Women who were smokers in 2003 did not have lower BMI values than nonsmokers. Mean serum cholesterol concentrations decreased markedly, whereas smoking habits did not significantly change. The prevalence of hypertension decreased by 8%, whereas that of diabetes remained stable at around 2%. Optimal risk factor status - no smoking, normotension and serum cholesterol <5 mmol l⁻¹ - was present in less than one in six women in 2003, and similar across BMI categories. CONCLUSION: The favourable decline in cholesterol levels and hypertension and the increase in leisure time physical activity were offset by an increase in obesity, triglyceride levels and experience of stress, with only a minority of participants (less than one in six) having an optimal level of risk factors with respect to smoking, serum cholesterol and hypertension in 2003. This applied also to overweight and obese women. In earlier cohorts, subjects with low BMI values were more often smokers, whereas the opposite is observed in recent cohorts. Thus, women who smoke no longer have the advantage of lower weight.

Obesity and trends in cardiovascular risk factors over 40 years in Swedish men aged 50.

OBJECTIVE: To study trends over 40 years in cardiovascular risk factors in normal weight, overweight and obese men, all aged 50 when examined. Design. Cross-sectional studies of five successive cohorts of men aged 50. SETTING: City of Göteborg, Sweden. SUBJECTS: Random population samples of altogether 3251 urban Swedish men born in 1913, 1923, 1933, 1943 and 1953. MAIN OUTCOME MEASURES: Anthropometry, cardiovascular risk factors, rates of nonsmoking, normotension and serum cholesterol <5 mmol L(-1) over four decades. RESULTS: Over 40 years, there was a net increase in body mass index (BMI) from 24.8 (SD = 3.2) to 26.4 (3.7) kg m(-2) (P < 0.0001), with an increase in the prevalence of obesity (BMI >or= 30 kg m(-2)) from 6.0% in 1963 to 13.8% in 2003. Favourable trends with respect to smoking, blood pressure and serum cholesterol were observed similarly amongst normal weight, overweight and obese men. In 1963, 24% of obese men were normotensive compared to 45% in 2003, and 6% had serum cholesterol <5 mmol L(-1) compared to 34% in 2003. Compared with obese men in 1963, men who were obese in 2003 had an odds ratio (OR) of 3.39 being a nonsmoker [95% confidence interval (CI): 1.56 to 7.36], 2.67 of being normotensive (1.23 to 5.83) and having serum cholesterol <5 mmol L(-1) of 8.30 (2.37 to 29.0). However, optimal risk factor status - no smoking, normotension and total serum cholesterol <5 mmol L(-1)- was still present in less than one in six men in 2003, similar across BMI categories. CONCLUSIONS: Obese Swedish men who are now in their fifties have much lower levels of other risk factors compared with obese men 40 years ago. This could contribute to explain why coronary heart disease death rates still are falling despite increasing rates of obesity.

Secular changes in cardiovascular risk factors and attack rate of myocardial infarction among men aged 50 in Gothenburg, Sweden. Accurate prediction using risk models.

AIMS: Coronary risk factor changes were related to attack rate of acute myocardial infarction (AMI). METHODS AND RESULTS: Cross-sectional population samples of 50-year-old men were examined every 10th year from 1963 to 2003. Attack rates of AMI were recorded from 1975 to 2004. Prevalence of smoking decreased from 56% in 1963 to 22% in 2003. Leisure time physical activity decreased (n.s.), while psychological stress remained the same. Diabetes prevalence increased from 3.6% to 6.6%. Body mass index (BMI) increased from 24.8 to 26.4 kg m(-2). Blood pressures decreased from 138.2/90.6 to 134.7/84.9 mmHg (P = 0.00001). Serum total cholesterol decreased from 6.42 to 5.50 mmol L(-1) (P = 0.0001), but serum triglycerides increased from 1.26 to 1.71 mmol L(-1) (P = 0.0001). The multivariable risk according to total cholesterol, blood pressure and smoking for AMI decreased from the set value 1.0 in 1963 to 0.418. From 1975-1979 to 2000-2004 attack rates for AMI for the age groups 35-44, 45-54 and 55-64 declined to 45%, 46% and 45%, respectively. The 28-day case fatality declined from 30%, 38% and 46% to 12%, 16% and 20%. CONCLUSION: The more than 50% decline in attack rate of AMI during 30 years was comparable with the decline in risk factors.

Serum lipids in fathers and sons at middle age: the study of sons to men born in 1913.

OBJECTIVE: To relate lipid levels in middle-aged men to that of their fathers at 50 years of age measured 30 years earlier. DESIGN AND SUBJECTS: In 1963, 855 men born in 1913 took part in a cardiovascular risk factor survey when they were at 50 years of age. In 1993, 475 sons to these men, aged 44-56, were invited to another examination; 263 of these men were examined (response rate: 56%) and compared with their 217 fathers when they were examined at 50 years of age in 1963. In the 1993 survey, 798 men aged 50, were also examined, from a general population sample of men born in 1943 (response rate: 55%). SETTING: City of Göteborg, Sweden. MAIN OUTCOME MEASURES: Serum lipids in sons as a function of lipids in their fathers. RESULTS: Compared with the men born in 1913, both sons and men born in 1943 had lower mean serum cholesterol, but higher body mass index (BMI) and serum triglycerides. There was a significant relation between serum cholesterol in sons and their fathers (r = 0.25; P < 0.0001). Amongst sons to fathers in the highest cholesterol quartile (>6.9 mmol x L(-1)), 37% had serum cholesterol above 6.5 mmol x L(-1), compared with 16% amongst sons to fathers in the lowest quartile (<5.7 mmol x L(-1)) [adjusted odds ratio 3.73 (1.52-9.12)]. Sons to fathers with the highest serum cholesterol levels had slightly lower BMI; otherwise there was no relation between serum cholesterol in the father and any other lifestyle or biological risk factor in the sons. Serum triglyceride concentration in the father was unrelated to any variable in the son. CONCLUSIONS: There was a moderately strong association between serum cholesterol concentration in fathers and sons at middle age. However, secular trends were also important in determining serum cholesterol concentrations in those born at a later period, indicating a major role of environmental factors.

A randomized, controlled, dose-guiding study of the oral direct thrombin inhibitor ximelagatran compared with standard therapy for the treatment of acute deep vein thrombosis: THRIVE I.

This randomized, controlled, multicentre study evaluated the efficacy and tolerability of the oral direct thrombin inhibitor ximelagatran, compared with a low-molecular-weight heparin (dalteparin) followed by warfarin, in the treatment of deep vein thrombosis (DVT) of the lower extremity. Patients with acute DVT received oral ximelagatran (24, 36, 48 or 60 mg twice daily) or dalteparin and warfarin for 2 weeks. Evaluation of paired venograms from 295 of 350 patients showed regression of the thrombus in 69% of patients treated with ximelagatran and 69% of patients treated with dalteparin and warfarin. Progression was observed in 8% and 3% of patients, respectively. Changes in thrombus size according to the Marder score were similar in all groups. Treatment discontinuation due to bleeding occurred in two patients receiving ximelagatran (24- and 36-mg groups) and in two patients receiving dalteparin and warfarin. Reduction in pain, edema and circumference of the affected leg was similar in all groups. Oral ximelagatran appears to be a promising alternative to current anticoagulant therapy to limit the progression of acute DVT, and it seems to possess a wide therapeutic window.

Secular changes in cardiovascular risk factors over 30 years in Swedish men aged 50: the study of men born in 1913, 1923, 1933 and 1943.

OBJECTIVES: To study secular trends in cardiovascular risk factors in men aged 50 over a period of 30 years. DESIGN: Cross-sectional studies of successive cohorts of men from 1963 to 1993. SETTING: City of Göteborg, Sweden. SUBJECTS: Four random population samples of men born in 1913, 1923, 1933 and 1943, aged 50 when they were examined in 1963, 1973, 1983, and 1993 (n = 855, 226, 776, and 798, respectively). MAIN OUTCOME MEASURES: Anthropometric measurements, blood pressure, serum cholesterol and triglycerides and smoking habits over three decades. RESULTS: Over 30 years, men increased in weight from a mean (SD) of 75.9 (11.0) kg to 82.8 (12.1) kg and gained 3.4 cm in height, with a net increase in body mass index from 24.8 (3.2) to 26.0 (3.4) kg m-2 (P < 0.0001), and a concomitant increase in waist circumference. The proportion of men who were overweight but not obese (BMI = 25-30 kg m-2) increased from 38 to 47%, whereas the prevalence of frank obesity (more than 30 kg m-2) increased from 6% in 1963 to 11% in 1993. Despite the increase in weight, mean systolic blood pressure fell by almost 10 mmHg (P < 0.0001). Mean serum cholesterol concentration decreased from 6.42 (1.12) to 5.88 (1.04) (P < 0.0001). Serum triglycerides increased from 1.26 (0.77) to 1.69 (1.04) mmol L-1 (P = 0.001). The proportion of men who smoked decreased from 56% in 1963 to 30% in 1993 (P < 0.0001). This was due more to an increase in smoking cessation rates than to an increase in the proportion of men who had never smoked. In particular, smokers and former smokers are now more obese than the corresponding categories 30 years ago and smokers are no longer leaner than men who have never smoked. CONCLUSIONS: Over a period of 30 years, serum cholesterol as well as systolic blood pressure and the prevalence of smoking decreased. This favourable decline in coronary risk factors was offset by an appreciable increase in body mass index and waist circumference.

Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: "the study of men born in 1913".

BACKGROUND: Risk factors for deep vein thrombosis and pulmonary embolism are mostly derived from case-control studies of hospitalized patients, and there are few long-term population-based studies. OBJECTIVE: To study the long-term risk factors for deep vein thrombosis and pulmonary embolism among middle-aged men. DESIGN: A prospective cohort study. SETTING: General community, "The Study of Men Born in 1913." SUBJECTS: A random population sample of 855 men, all aged 50 years at baseline. MAIN OUTCOME MEASURES: Eight-hundred fifty-five men participated in a screening examination in 1963 at the age of 50 years, and 792 of these men were reexamined in 1967 at the age of 54. All the men were followed up with periodic examinations until the age of 80. Objective methods were used to ascertain a diagnosis of deep vein thrombosis or pulmonary embolism. RESULTS: Waist circumference (P=.004) and smoking (P = .02) predicted a venous thromboembolic event in multivariate survival analysis. Men in the highest decile of waist circumference (> or =100 cm) had an adjusted relative risk of 3.92 (95% confidence interval, 2.10-7.29; P<.001) compared with men with a waist circumference of less than 100 cm. For men who smoked 15 g of tobacco (15 cigarettes) a day or more, the adjusted relative risk was 2.82 (95% confidence interval, 1.30-6.13; P= .009) compared with nonsmokers. CONCLUSIONS: Smoking and abdominal obesity were independent risk factors for venous thromboembolic events during follow-up. In addition to the prevention of smoking and obesity, a more aggressive strategy regarding the use of prophylactic agents among smokers and obese patients, in various risk situations, may be justified.

Prevalence of APC resistance and its relationship to arterial and venous thromboembolism in a general population sample of elderly Swedish men: The Study of Men Born in 1913.

BACKGROUND: Most studies of hereditary resistance to activated protein C (APC resistance) as a risk factor for venous thromboembolism are derived from case-control studies of hospitalized patients, whilst the importance of this condition in the general population has been only sparsely investigated. OBJECTIVE: To study the prevalence of APC resistance and its relationship to morbidity and mortality in a general population sample of elderly men. DESIGN: Cross-sectional and prospective follow-up study. SETTING: General community: The Study of Men Born in 1913. SUBJECTS: A random population sample of 404 men, all 75 years of age. MAIN OUTCOME MEASURES: Four hundred and four men participated in a screening examination in 1988. The APC ratio was analysed in 382 of them. All the men were followed up for 5 years. Medical records were reviewed for all the men with a history of deep vein thrombosis, pulmonary embolism, myocardial infarction or stroke. RESULTS: Twenty-five men (6.5%) were found to have APC resistance. The incidence of venous thromboembolism, myocardial infarction or stroke did not differ between men with or without APC resistance, either retrospectively or during follow-up. Only two men experienced a deep vein thrombosis before the age of 80 and there was no case of pulmonary embolism. Mortality during 5 years of follow-up did not differ between men with and without APC resistance. CONCLUSION: The prevalence of APC resistance was 6.5% in this study of Swedish men. Although the size of the population sample is somewhat small, the study shows that, amongst elderly men, the association between APC resistance and venous thromboembolic disease was weak and men with this hereditary condition did not have any increase in morbidity or mortality compared with men without APC resistance.

Falls risk factors in an acute-care setting: a retrospective study.

Research findings have been contradictory regarding risk factors for falls in the acute-care setting. Identification of factors that place individuals at risk of falling in this setting are a priority because falls result in high morbidity and mortality and thus increased healthcare costs. The purpose of this study was to extend knowledge beyond the known risk factors of age and medical diagnosis by comparing the characteristics of 301 adults who fell while hospitalized with a matched sample of adults who did not fall while hospitalized. A descriptive, retrospective, comparative design was used. The fall and non-fall group were matched on age and primary medical diagnosis at the time of discharge. Data were collected from hospital incident reports and medical records. Logistic regression for matched groups identified 5 risk factors, as follows. Incontinence. The odds of falling were 11.3 (CI = 3.85, 33.05) times greater for those who were incontinent than for those who were not incontinent. Long hospital stay. The odds of falling were 9.9 (CI = 4.89, 19.88) times greater for those hospitalized 19 days or longer than for those hospitalized less than 19 days. Dependency for ambulation. The odds of falling were 6 (CI = 2.83, 12.84) times greater for those who were dependent for ambulation than for those who were independent. Independency for hygiene. The odds of falling were 2.5 (CI = 1.23, 4.88) times greater for those who were independent for hygiene than for those who were dependent. Lack of regular exercise. The odds of falling were twice as high (CI = 1.00, 3.82) for those who did not exercise regularly as for those who exercised regularly. These findings suggest that ongoing assessment may be more important than the admission assessment in identifying risk factors for falls in the acute-care setting. No 2 studies have found exactly the same set of risk factors, although some findings are consistent across studies. This suggests that those risk factors that are consistent across studies may identify persons who are at the greatest risk for falls and that other risk factors for falls are specific to a patient population.

Deep vein thrombosis and pulmonary embolism in the general population. 'The Study of Men Born in 1913'.

BACKGROUND: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common public health problems. Still, little is known about the epidemiology and the natural history of venous thromboembolism. METHODS: In the Study of Men Born in 1913, 855 men were followed up prospectively from the age of 50 years to the age of 80 years. Several cross-sectional samples, also of men born in 1913, were studied at the ages of 50, 54, 60, 67, 75, and 80 years. Objective methods were used to ascertain a diagnosis of DVT or PE, and all were confirmed by hospital records or autopsy reports. The follow-up rate in the longitudinal study was 98.2%. RESULTS: In the longitudinal study, the incidence of DVT was 182 per 100,000 observation-years. Corresponding incidence rates were 98 for nonfatal PE, 107 for fatal PE, and 387 for all thromboembolic events. The cumulative probability for a venous thromboembolic event at different ages was estimated to be 0.5% by the age of 50 years and 10.7% by the age of 80 years. In the cross-sectional studies, a history of confirmed venous thromboembolism was found in 0.5% of the men at age 50 years, 0.9% at age 54 years, 1.3% at age 60 years, 2.0% at age 67 years, 4.5% at age 75 years, and 3.8% at age 80 years. CONCLUSIONS: The results indicate a high incidence of DVT and PE in the general population. The incidence of thromboembolic events increases with age. The rate of fatal PE seems to be higher than estimated before, and PE constitutes almost 5% of all deaths during follow-up.

Overview of the safety of felodipine based on clinical trials in patients with hypertension.

All clinical studies of at least 1 week's duration with felodipine in patients with hypertension were included in a safety analysis. The major finding was that felodipine does not increase mortality or the incidence of major cardiovascular events and that the data indicate a favorable effect.

Mental impairment and utilization of community services: a study of the elderly in a parish of Stockholm.

Before the implementation of the health care reform of 1992 (The Adel Reform), a study of the frequency of mental impairment of people in different residential and care services was conducted in a parish of Stockholm. All residents, 65 years or older, registered with Primary Care Centres, Geriatric Hospitals and other institutions were assessed with respect to cognitive function according to the seven stage "Global Deterioration Scale" (GDS). The age-specific frequencies of mental impairment were similar to prevalences reported in earlier studies. The frequency of cognitive dysfunction of non-institutionalized and institutionalized elderly was 42% and 52%, respectively, and higher for women than for men. There was considerable variation in the prevalence of cognitive dysfunction among subjects in different types of accommodation. For the different stages of mental impairment the average age was about the same. With increasing need and demand for services, and limited resources, these variations in cognitive dysfunction have important implications for structuring appropriate support systems in a population with a rapidly rising proportion of elderly people.

Foot pathology and risk factors for diabetic foot disease in elderly men.

We examined 3 groups of elderly men; men with diabetes and previous or present foot ulcers, men with diabetes, and men without diabetes. In the foot diseased group, diabetes duration was longer (18 +/- 11 vs 8 +/- 7 years), insulin treatment was more common (86% vs 7%), fasting blood glucose and HbA1c were significantly higher (10.5 +/- 4.0 mmol/1, 8.4% +/- 1.6%) than in the diabetic control group (8.3 +/- 3.4 mmol/l, 7.4 +/- 1.7%). Men in the foot diseased group were taller than men in the diabetic group and non-diabetic men (1.79 vs 1.74 m) but not more obese (BMI 26-27 kg/m2 in all three groups). Current or previous alcoholic problems were more common in the foot diseased group (32%) compared to the control diabetic group (9%) and the non-diabetic group (10%). Diabetic patients with known foot disease had more often callosities, absent hair growth, dry skin and redness, compared to the other groups. Psychosocial problems (alcohol and divorce), long standing diabetes duration and poor metabolic control seem to be of importance for the development of diabetic foot ulcers.

New antiinflammatory compounds that inhibit tumor necrosis factor production: probable interaction with protein kinase C activation.

We have previously described a family of benzamide derivatives that showed antiinflammatory activity in vivo on carragenin-induced paw edema and experimental cerebral edema. Those compounds inhibited eicosanoids production from activated macrophages (M phi) without inhibiting cyclooxygenase. To further investigate their antiinflammatory activity and compare it to that of classical cyclooxygenase inhibitors, we analyzed their effect on the production of a major proinflammatory cytokine, tumor necrosis factor (TNF-alpha), by in vitro-activated peritoneal macrophages. We show that, in marked contrast with ibuprofen, flurbiprofen and indomethacin which all significantly enhanced TNF production, the two benzamide derivatives tested, JM34 and JM42, significantly inhibited TNF-alpha production by zymosan or lipopolysaccharide-activated M phi. Those compounds did not interfere with the calcium-dependent pathway because they did not affect TNF production of either mice peritoneal M phi or human T cell clones induced by the calcium ionophore A23187 alone. More likely, these benzamide derivatives acted mainly at the level of the protein kinase C (PKC) pathway because: 1) After treatment of M phi with PKC inhibitors which significantly inhibited TNF production, our compounds showed no additional inhibition. 2) Our compounds significantly inhibited TNF production of M phi stimulated with the phorbol ester phorbol di-butyrate alone or in combination with A23187. 3) After depletion of PKC by prolonged phorbol di-butyrate treatment of M phi, inhibition of TNF production by our compounds was markedly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

The value of prostate specific antigen in early diagnosis of prostate cancer: the study of men born in 1913.

PURPOSE: We attempt to elucidate the performance of serum prostate specific antigen (PSA) as a screening test for prostate cancer. MATERIALS AND METHODS: We analyzed sera stored since 1980 in a nested case-control study. RESULTS: The 36 patients with prostate cancer had a markedly greater mean serum PSA level than did 68 subjects without cancer (22.71 versus 2.67, respectively, p < 0.0001). Among the controls 24% had a serum PSA of greater than 4.0 micrograms/l. A serum PSA value exceeding 4.0 micrograms/l. in 1980 was associated with a 20-fold excess risk of cancer between 1981 and 1986, and an 8-fold risk between 1987 and 1991. CONCLUSIONS: Diagnosis of clinically significant prostate cancer can be advanced substantially by serum PSA testing. However, the large number of high serum PSA values in men who remained free of clinical disease emphasizes the need for a more specific screening test.

Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year.

OBJECTIVES: We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. BACKGROUND: Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. METHODS: A total of 620 patients were studied: 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for > or = 3 months and 314 to conventional therapy. RESULTS: The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 +/- 4.1 to 9.6 +/- 3.3 mmol/liter (mean +/- SD) in the infusion group during the 1st 24 h, and from 15.7 +/- 4.2 to 11.7 +/- 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046]; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). CONCLUSIONS: Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.

Antiinflammatory mechanism of cordiachromene A action.

The mechanism of antiinflammatory action of cordiachromene A, isolated from the chloromethylenic extract of the ascidian Aplidium antillense or chemically synthesized, was studied using different in vivo and in vitro inhibition tests on enzymes of the cyclooxygenase cascade. Cordiachromene A inhibits prostacyclin synthesis and arachidonic acid metabolism but not phospholipase A2 and peroxidase. The mechanism of action, already known to be stereospecific, operates by cyclooxygenase inhibition.

Influence of alkyl chain lengths in dialkylglycerophosphocholines towards phospholipase A2 inhibition in macrophages.

Rat peritoneal macrophages were cultured with a specific and potent phospholipase A2 activator A 23187, with 1-stearoyl-2-[3H]arachidonoyl-sn-GPC as source of [3H] arachidonic acid, and with a dialkyl-GPC, at 2, 10 or 20 microM. Four dialkyl-GPCs were prepared by chemical synthesis. Position 2 of rac-glycerol was alkylated with an alkane chain of 8 carbons and position 1 was alkylated with various alkane chains (8, 10, 12, or 16 carbons). [3H] arachidonic acid was split, then recovered with cell nonesterified fatty acids and nonphosphorous glycerolipids after endocellular phospholipase A2 activity. It was also recovered with fatty acids and eicosanoids isolated from culture medium. Inhibition of fatty acid release and eicosanoid synthesis depended on mixed chain dialkyl-GPC structures. The highest inhibitory effect on arachidonic acid release was reached with 1-decyl-2octyl-GPC and was practically as high in culture medium (IC50 at 5 microM) as in cells (IC50 at 4 microM). 1,2-di-octyl-GPC and 1-dodecyl-2-octyl-GPC had weaker inhibitory effects (but higher in culture medium than in cells). The asymmetrical 1-hexadecyl-2-octyl-GPC poorly affected enzyme activity.