Frequency of family history of acute myocardial infarction in patients with acute myocardial infarction. Argentine FRICAS (Factores de Riesgo Coronario en America del Sur) Investigators.

The relation between family history of acute myocardial infarction (AMI) and the risk of AMI was analyzed using data of a case-control study conducted in Argentina between 1992 and 1994. Case patients were 1,060 subjects with AMI admitted to 35 coronary care units, and controls were 1,071 subjects admitted to the same network of hospitals where cases had been identified, for a wide spectrum of acute conditions unrelated to known or likely risk factors for AMI: 31% of cases versus 15% of controls reported > or = 1 first-degree relative with history of AMI. Compared with subjects without family history of AMI, the odds ratio (OR) of AMI, after allowance for age, sex, cholesterolemia, smoking, diabetes, hypertension, body mass index, education, social class, and physical exercise, was 2.18 (95% confidence interval [CI] 1.74 to 2.74) for those with family history of AMI. The OR was 2.04 (95% CI 1.60 to 2.60) for subjects with 1 relative, and 3.18 (95% C 1.86 to 5.44) for those reporting > or = 2 relatives with AMI. In women the OR for any family history of AMI was 2.83, and in men 2.01. The association was of similar magnitude if the mother (OR 1.98), the father (OR 2.13), or a sibling (OR 2.48) had had an AMI. The association with family history was stronger at a younger age because the OR for subjects reporting > or = 2 more relatives with a history of AMI was 4.42 for subjects aged < 55 years, and 3.00 for those aged > or = 55 years. The association between AMI and family history of AMI was consistent across separate strata of education, social class, smoking, and serum cholesterol, but was less strong in subjects with history of diabetes and hypertension. When the interaction of known risk factors with family history of AMI was analyzed, hypercholesterolemia, hypertension, and smoking had approximately multiplicative effects on the relative risk. The OR was 4.50 for subjects with family history and cholesterol > or = 240 ml/dl, 4.52 for those with hypertension, and 5.77 for current smokers with family history of AMI. Thus, this study confirms that a family history of AMI is a strong and independent risk factor for AMI. In this population from Argentina, family history accounted for 14% of all cases of AMI in men and 26% in women.

Systemic leakage and side effects of tumor necrosis factor alpha administered via isolated limb perfusion can be manipulated by flow rate adjustment.

BACKGROUND: The tolerated systemic dose of recombinant tumor necrosis factor alpha (rTNF-alpha) is very limited, since its administration leads to a severe septic shock-like condition. Its implementation in isolated limb perfusion (ILP) for metastatic melanoma or advanced soft-tissue sarcoma confined to the limb facilitates doses of rTNF-alpha 10 times higher than the systemic tolerated dose. However, with the traditional high flow rate used in ILP, systemic leakage and side effects are not eliminated. OBJECTIVE: To determine if a lower perfusion flow rate would reduce leakage and consequently toxic effects. METHODS: Isolated limb perfusion was performed for melanoma and soft-tissue sarcoma confined to the limb using a flow rate of 869 +/- 122 mL/min in nine patients (group 1) and a lower rate of 286 +/- 62 mL/min in six patients (group 2). RESULTS: The systemic leakage rate was 12.5% +/- 2.9% in group 1, compared with 2.3% +/- 1.0% in group 2 (P = .003). Peak TNF-alpha levels were 29,000 +/- 2700 pg/mL in group 1, higher than 1580 +/- 1355 pg/mL in group 2 (P = .02). The tachycardia, hypotension, increased cardiac output, decreased systemic vascular resistance, bilirubinemia, elevation of liver enzyme levels, hypocholestrolemia, thrombocytopenia, and prolongation of prothrombin and partial thromboplastin times all observed in group 1 were significantly attenuated or eliminated in group 2. The limb PO2, PCO2, pH, and viability remained similar in both groups. Also, the tumor response rate remained high and was unaffected by the decrease in flow rate. CONCLUSIONS: Decreasing perfusion flow rate during ILP results in diminished leakage of TNF-alpha. Consequently, the systemic hemodynamic, metabolic, and hematologic toxic effects are virtually abolished.