Multimodal therapy with intravenous biweekly leucovorin, 5-fluorouracil and irinotecan combined with hepatic arterial infusion pirarubicin in non-resectable hepatic metastases from colorectal cancer (a European Association for Research in Oncology trial).

BACKGROUND: The purpose of this study was to evaluate the tolerance and efficacy of combining i.v. irinotecan, 5-fluorouracil (5-FU) and leucovorin (LV) with hepatic arterial infusion (HAI) of pirarubicin in non-resectable liver metastases from colorectal cancer. PATIENTS AND METHODS: Thirty-one patients were included in a phase II trial with i.v. irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks. In most cases HAI was administered via a percutaneous catheter. RESULTS: The main grade 3/4 toxicity was neutropenia, encountered in 78% of the patients. When all patients were considered in the analysis, tumour response rate was 15 out of 31 [48%; 95% confidence interval (CI) 32% to 65%]. Liver resection was made possible in 11 patients (35%; 95% CI 21% to 53%). There were no toxic death. Median overall survival was 20.5 months, and median progression-free survival was 9.1 months. In patients with completely resected metastases, median overall survival was not reached and median progression-free survival was 20.2 months. CONCLUSION: The multimodality approach used in the present study was well-tolerated and yielded dramatic responses. An aggressive approach combining i.v. and HAI chemotherapy deserves further investigation.

Moderate intake of n-3 fatty acids is associated with stable erythrocyte resistance to oxidative stress in hypertriglyceridemic subjects.

BACKGROUND: The important triacylglycerol-lowering capacity of n-3 fatty acids is counterbalanced by their inherent sensitivity to oxidation. Inconsistent results about the latter have been reported in hypertriglyceridemic individuals. After incorporation into cell membranes, n-3 fatty acids may alter membrane-related functions. In view of the distinct composition of hypertriglyceridemic membranes and the prooxidant status in this condition, it can be surmised that cell enrichment with the oxidizable n-3 fatty acids will be associated with an increased hemolytic process. OBJECTIVE: We sought to evaluate the effect of fish oil consumption on n-3 fatty acid incorporation into erythrocyte membranes and subsequent ex vivo oxidative-stress-induced hemolysis in normotriglyceridemic and hypertriglyceridemic subjects. DESIGN: Sixteen normotriglyceridemic and 12 hypertriglyceridemic subjects were given 6 g fish oil/d for 8 wk. Blood samples were collected before and 4 and 8 wk after treatment. Resistance to 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced hemolysis was assayed in fresh erythrocyte suspensions, and erythrocyte samples were stored at -70 degrees C for later analysis of cholesterol, hemoglobin, fatty acids, vitamin E, and glutathione peroxidase activity. RESULTS: Fish oil supplementation induced n-3 fatty acid incorporation in normotriglyceridemic and hypertriglyceridemic erythrocyte membranes without decreasing their resistance to AAPH. n-3 Fatty acids significantly protected normotriglyceridemic but not hypertriglyceridemic erythrocytes against hemolysis. In normotriglyceridemic subjects only, the higher resistance to hemolysis correlated with changes in cell vitamin E. CONCLUSION: Although they exhibit a high susceptibility to oxidation, n-3 fatty acids may preserve membrane integrity and represent an added benefit in the treatment of hypertriglyceridemic patients.

Plasma total homocysteine in healthy subjects: sex-specific relation with biological traits.

Fasting plasma total homocysteine (tHcy) concentration was measured in 380 men and 204 women selected for health on the basis of clinical history, physical examination, and normal results of a biochemical profile. We sought to define tHcy reference values in healthy individuals and to determine relations between tHcy and plasma folic acid, vitamin B-12, and pyridoxal phosphate (vitamin B-6) concentrations. Men had significantly higher plasma tHcy than women (9.7 +/- 4.9 compared with 7.6 +/- 4.1 mumol/L, x +/- SD) and lower folate concentrations (8.6 +/- 5.2 compared with 9.8 +/- 6.6 nmol/L, P < 0.05). Significant correlations were found between tHcy and uric acid, creatinine, albumin, folate, and vitamin B-12 concentrations. There was no correlation with age, body mass index, blood pressure, glucose, and total and lipoprotein lipids. When divided in quartiles of vitamin concentrations, subjects with the lowest vitamin B-12 and folate values had significantly higher tHcy concentrations than those in the other three quartiles. Interestingly, after exclusion of subjects in the lowest quartiles of folate and vitamin B-12 concentration, correlations between tHcy and vitamin concentrations were no longer observed, except for vitamin B-12 in men. Stepwise-multiple-regression analyses showed that the sex-specific influence of biological variables on tHcy concentrations was twice as important in healthy women than in healthy men. This study emphasizes the significance of sex-associated differences in the biology of homocysteine and underlines the importance of considering these in the determination of threshold values.

Prevention of recurrent acute pancreatitis in patients with severe hypertriglyceridemia: value of regular plasmapheresis.

The association between acute pancreatitis and severe hypertriglyceridemia has long been recognized. We report two cases of severe primary hypertriglyceridemia (types 1 and V) with recurrent acute pancreatitis. In both patients, observance of appropriate diet and drug therapy was insufficient. Recurrent episodes of pancreatitis were precipitated by dietary fat or alcohol abuse. A plasmapheresis was performed every 4 weeks to decrease the incidence of pancreatitis. It appears that plasmapheresis is a safe and highly effective method for quickly removing serum triglycerides. Moreover, plasma-pheresis may be useful for preventing acute pancreatitis.

[Homocysteine: relations to ischemic cardiovascular diseases]. / L'homocystéine: ses liens avec les maladies cardiovasculaires ischémiques.

Homocysteine, a sulfur-containing amino acid, is an intermediate metabolite of methionine. Patients with homocystinuria and severe hyperhomocysteinemia develop premature arteriosclerosis and arterial thrombotic events, and venous thromboembolism. Studies suggest that moderate hyperhomocysteinemia can be considered as an independent risk factor in the development of premature cardiovascular disease. In vitro, homocysteine has toxic effects on endothelial cells. Homocysteine can promote lipid peroxidation and damage vascular endothelial cells. Moreover, homocysteine interferes with the natural anticoagulant system and the fibrinolytic system. Homocysteinemia should be known in patients with premature vascular diseases, especially in subjects with no risk factors. Folic acid, vitamin B6 can lower homocysteine levels.

Postprandial lipoprotein clearance in type 2 diabetes: fenofibrate effects.

Lipoprotein abnormalities [mainly high levels of very-low-density lipoprotein triglycerides (TG) and low levels of high-density lipoprotein cholesterol] increase the risk of cardiovascular disease in Type 2 diabetic patients. Moreover, only fasting TG and central obesity appear to independently predict mortality from CAD in glucose-intolerant and diabetic subjects. It is noteworthy that fasting lipid levels in these patients are often relatively unaffected, and that plasma TG may remain < 2 g/l, the cutoff point currently considered to define moderate hypertriglyceridemia. Our study of postprandial lipaemia shows that lipid intolerance (a greater increase of postprandial TG and a slower return towards basal levels) was almost always present in these patients, enabling us to detect atherogenic changes in plasma lipoproteins. Preliminary results indicate that fenofibrate treatment in Type 2 diabetes under optimised metabolic control improves not only fasting lipid levels but also postprandial lipaemia and associated abnormalities in lipoprotein levels and composition.

[Lipoprotein (a)]. / Lipoprotéine (a).

Lipoprotein(a) or Lp(a) is similar to low density lipoproteins (LDL), but also contains a large glycoprotein molecule called apo-lipoprotein(a) or apo(a). The lipid composition of Lp(a) is nearly identical to that of LDL. The structure of apo(a) is similar to that of plasminogen. Several genetic polymorphisms have been described for apo(a). The increasing interest in Lp(a) is due to the positive correlation which exists between the plasma level of Lp(a) and the incidence of ischaemic heart disease. Plasma Lp(a) level varies greatly from one individual to another and is basically dependent on genetic factors, especially for the isoforms of apo(a). A level above 30 mg.dl is associated with increased risk of atherosclerosis-related diseases. There are few treatments which are effective in significantly reducing raised levels of Lp(a).

[Effect of the captopril-hydrochlorothiazide combination on blood lipids. Study in a population of hypertensive hyperlipidemic patients]. / Influence de l'association captopril-hydrochlorothiazide sur les lipides sanguins. Etude sur une population d'hypertendus hyperlipidémiques.

In this placebo-controlled, randomized double-blind, parallel study the effects of the fixed captopril 50 mg + hydrochlorothiazide (HCTZ) 25 mg combination on plasma lipids were assessed in 42 hypertensive, type IIa or IIb hyperlipidaemic patients on diets. Some patients received oral hypolipidaemic treatment and some did not. Blood pressure and plasma lipids levels were measured before and after 1, 2 and 3 months of treatment. From the first month onward blood pressure decreased more in the treated group than in the placebo group (P < 0.05). Neither the combination nor the placebo altered the following parameters of lipid metabolism: total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein A1 and apolipoprotein B. The combination was well tolerated; 2 patients in each group had one or several adverse events. The results of this study show that treatment with the captopril-HCTZ combination in hypertensive, hyperlipidaemic patients has no influence on the normolipidaemic effects of diet and lipid-lowering treatment.

[Initial and mid-term results of coronary angioplasty in early post-infarction unstable angina]. / Résultats initiaux et à moyen terme de l'angioplastie coronaire dans l'angor instable précoce post-infarctus.

The aim of this study was to assess the immediate efficacy and the medium-term risks and results of percutaneous transluminal coronary angioplasty (PTCA) in early post-infarction unstable angina. Thirty-six patients were included for a series of 248 consecutive PTCA procedures performed between December 1985 and January 1989. The average age was 56 years (range 35 to 84 years). The initial infarct was anterior (N = 16), inferior (N = 15), lateral (N = 5), without a Q wave (N = 22), transmural (N = 14) and treated by thrombolysis in 42 p. 100 of cases. The interval between initial infarction and PTCA was 16 +/- 3 days. A primary success was obtained in 33 cases (92%). One patient died of electromechanical dissociation at the beginning of the procedure. Two infarcts occurred due to acute coronary occlusions. None of the patients required emergency coronary bypass surgery. The specific risk of PTCA in early post-infarction unstable angina is acute coronary occlusion. This complication was observed in 9 patients (25%) and it required immediate repeat PTCA, associated with thrombolytic therapy in four cases. Coronary occlusion was more common in patients with transmural infarcts than in those without Q-waves (43% vs 14%; p less than 0.01) and in patients treated initially by thrombolysis compared with those not treated by thrombolysis (40% vs 15%; p less than 0.05). No fatalities or reinfarctions occurred during follow-up (average 9 +/- 8 months, range 2 to 35 months). A good clinical result was maintained in 71 per cent of patients treated by PTCA alone. Seven repeat PTCA procedures and 3 coronary bypass operations were performed during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)