The association of fasting plasma sulfur-containing compounds with BMI, serum lipids and apolipoproteins.

BACKGROUND AND AIM: Sulfur amino acids are recognized as potent modulators of lipid metabolism. Plasma total cysteine (tCys) is associated with fat mass, obesity and serum LDL-cholesterol and apolipoprotein (Apo)-B in large population studies. It is not known how fasting plasma concentrations of cysteine precursors and products relate to these associations in humans, given that sulfur-containing compounds (SCC) influence rodent weight gain and serum lipids. METHODS AND RESULTS: We investigated the cross-sectional associations of fasting plasma SCC (methionine, total homocysteine, cystathionine, tCys, taurine and total glutathione) with BMI and fasting serum lipids and apolipoproteins in 854 men and women with and without cardiovascular disease (CVD). In multiple linear regression analysis adjusted for age, gender, CVD and other SCC, neither methionine, taurine, nor total glutathione was associated with BMI. Plasma taurine was, however, inversely related to HDL-cholesterol (partial r = -0.12, p = 0.004) and its associated apoA1 (partial r = -0.18, p < 0.001). Plasma cystathionine correlated positively with triglycerides and BMI, while tCys positively correlated with total cholesterol, LDL-cholesterol (partial r = 0.20, p < 0.001) and its associated apoB. The associations of SCC with serum lipids were independent of BMI. tCys was also independently associated with BMI (partial r = 0.20, p < 0.001) after adjustment for other SCC, glucose, lipids and apolipoproteins. CONCLUSIONS: Fasting tCys is associated with BMI independently of metabolically related SCC. Elevation of plasma SCC is generally associated with an unfavorable lipid profile. The negative relations of plasma taurine with HDL-C and apoA1 deserve further investigation.

Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.

CONTEXT: Elevated plasma homocysteine is a known risk factor for atherosclerotic vascular disease, but the strength of the relationship and the interaction of plasma homocysteine with other risk factors are unclear. OBJECTIVE: To establish the magnitude of the vascular disease risk associated with an increased plasma homocysteine level and to examine interaction effects between elevated plasma homocysteine level and conventional risk factors. DESIGN: Case-control study. SETTING: Nineteen centers in 9 European countries. PATIENTS: A total of 750 cases of atherosclerotic vascular disease (cardiac, cerebral, and peripheral) and 800 controls of both sexes younger than 60 years. MEASUREMENTS: Plasma total homocysteine was measured while subjects were fasting and after a standardized methionine-loading test, which involves the administration of 100 mg of methionine per kilogram and stresses the metabolic pathway responsible for the irreversible degradation of homocysteine. Plasma cobalamin, pyridoxal 5'-phosphate, red blood cell folate, serum cholesterol, smoking, and blood pressure were also measured. RESULTS: The relative risk for vascular disease in the top fifth compared with the bottom four fifths of the control fasting total homocysteine distribution was 2.2 (95% confidence interval, 1.6-2.9). Methionine loading identified an additional 27% of at-risk cases. A dose-response effect was noted between total homocysteine level and risk. The risk was similar to and independent of that of other risk factors, but interaction effects were noted between homocysteine and these risk factors; for both sexes combined, an increased fasting homocysteine level showed a more than multiplicative effect on risk in smokers and in hypertensive subjects. Red blood cell folate, cobalamin, and pyridoxal phosphate, all of which modulate homocysteine metabolism, were inversely related to total homocysteine levels. Compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk of vascular disease, a proportion of which was attributable to lower plasma homocysteine levels. CONCLUSIONS: An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia. It powerfully increases the risk associated with smoking and hypertension. It is time to undertake randomized controlled trials of the effect of vitamins that reduce plasma homocysteine levels on vascular disease risk.

[Hemodynamic effects of captopril in acute infarct of the anterior myocardium]. / Efeitos hemodinâmicos do captopril no enfarte agudo do miocárdio anterior.

OBJECTIVE: Evaluation of haemodynamic effects after sublingual administration of 25 mg of captopril in patients with Acute Anterior Myocardial Infarction within the first 48 hours. DESIGN: Determination of basal parameters and 30 minutes after 25 mg of captopril. SETTING: Patients admitted in the ICU with Anterior Myocardial Infarction diagnosis. PATIENTS: 41 consecutive patients; 22 patients submitted to thrombolysis with streptokinase; 19 patients submitted to conventional therapy. RESULTS: A) In the whole group: No significant change in the HR, PAP, CI, SI, MAP, SVR, PR. RA and CWP were reduced. B) In thrombolysed patients: No significant change in HR, RA, PAP, CWP, MAP, SVR, PR. CI and SI were significantly increased. C) In non-thrombolysed patients: No significant change in HR, PAP, CI, SI, SVR, PR. RA, CWP and MAP were reduced. CONCLUSION: 1. We found no significant hypotension with sublingual captopril in Acute Myocardial Infarction. 2. Non-thrombolysed patients showed a greater reduction of arterial pressure. 3. Thrombolysed patients had significant increases in systolic function indices.

Primary chemotherapy with mitoxantrone and prednisone in advanced breast carcinoma. A phase II study.

Thirty-seven evaluable patients with progressive disseminated breast carcinoma were treated with a combination of mitoxantrone 14 mg/m2 i.v. every 3 weeks plus prednisone 20 mg/m2 p.o. daily with a reducing dose over several weeks. Thirteen of 37 patients (35%) achieved an objective response with two complete regressions. The median duration of response was 7 months and the median duration of survival 14 months. The cardiac function of all patients was monitored by serial left ventricular ejection fraction, at rest and after stress, and 3-monthly thereafter. Ten patients showed a deterioration in the ejection fraction after a minimum cumulative dose of 86 mg/m2 (six cycles), but only four developed clinical cardiac failure which was easily reversible after stopping mitoxantrone. Leucopenia was the dose-limiting toxicity. Nausea and/or vomiting were generally mild and transient. Alopecia was minimal. These results confirmed that this combination is effective and well tolerated in the treatment of disseminated breast carcinoma, and cardiotoxicity can be avoided with adequate monitoring of the left ventricular ejection fraction after six cycles of therapy (86 mg/m2).

A comparison of two doses of adriamycin in the primary chemotherapy of disseminated breast carcinoma.

Forty-eight patients with advanced breast carcinoma who had not received prior chemotherapy (minimum follow up 21 months) were randomised to receive either adriamycin 70 mg m-2 i.v. 3-weekly for 8 cycles (Regimen A) or adriamycin 35 mg m-2 i.v. 3-weekly for 16 courses (Regimen B). Objective responses were seen in 14/24 (58%) patients with regimen A (4 complete) and 6/24 (25%) with regimen B (1 complete) (P less than 0.02). The median duration of response was 14 months with regimen A and 6.5 months with regimen B. The median duration of survival was 20 months and 8 months respectively (P less than 0.01). The toxicity was similar with each regimen. There was no evidence of deterioration in left ventricular ejection fraction nor congestive heart failure in any patient. It is concluded that when given at 3-weekly intervals adriamycin is a more effective treatment for advanced breast cancer at higher rather than lower dosage.