Cigarette smoking is associated with increases in plasma triglycerides and decreases in plasma high density-lipoprotein-cholesterol concentration. These changes not only increase risk of coronary heart disease but also are secondary to resistance to insulin-stimulated glucose uptake or hyperinsulinaemia. To see whether there is a relation between cigarette smoking and insulin-mediated glucose uptake we measured plasma lipid and lipoprotein concentrations, plasma glucose and insulin response to an oral glucose challenge, and insulin-mediated glucose uptake in 40 matched healthy volunteers (20 non-smokers, 20 smokers). Smokers had significantly higher mean (SEM) very-low-density-lipoprotein triglycerides (0.66 [0.10] vs 0.39 [0.03] mmol/l, p less than 0.02) and cholesterol (0.45 [0.06] vs 0.23 [0.04] mmol/l, p less than 0.005) concentrations and lower high-density-lipoprotein cholesterol concentrations (1.16 [0.05] vs 1.51 [0.08] mmol/l, p less than 0.001). Although plasma glucose concentrations in response to the oral glucose load were similar in the two groups, plasma insulin response of the smokers was significantly higher (p less than 0.001). Finally, smokers had higher steady-state plasma glucose concentrations in response to a continuous infusion of glucose, insulin, and somatostatin (8.4 [0.2] vs 5.0 [0.3] mmol/l, p less than 0.001), despite similar steady-state plasma insulin concentrations. The findings show that chronic cigarette smokers are insulin resistant, hyperinsulinaemic, and dyslipidaemic compared with a matched group of non-smokers, and may help to explain why smoking increases risk of coronary heart disease.

The effect of breastfeeding on fertility is well known; however, its use as a method of family planning was, until recently, untested. In 1988, the Bellagio Consensus Conference proposed guidelines that became the basis for a method of family planning called the lactational amenorrhoea method (LAM). The principle of LAM is that a woman who continues to fully or nearly fully breastfeed her infant and who remains amenorrhoeic during the first 6 months postpartum is protected from pregnancy during that time. We have assessed this method in the context of a breastfeeding support intervention study of 422 middle-class women in urban Santiago, Chile. The cumulative 6-month life-table pregnancy rate was 0.45% among women who relied on LAM as their only family planning method (1 woman pregnant in month 6). The findings indicate that LAM, with its high acceptance and efficacy, is a viable method of family planning and can safely serve as an introductory method for breastfeeding women.

Oxidative modification of LDL renders it immunogenic and autoantibodies to epitopes of oxidised LDL, such as malondialdehyde (MDA)-lysine, are found in serum and recognise material in atheromatous tissue. However, there has been no prospective study to assess the importance of oxidised LDL among patients with vascular disease. We compared the titre of autoantibodies to MDA-modified LDL and native LDL in baseline serum samples of 30 eastern Finnish men with accelerated two-year progression of carotid atherosclerosis and 30 age-matched controls without progression. Neither group had specific antibody binding to native LDL. A titre was defined as a ratio of antibody binding to MDA-LDL/binding to native LDL. Cases had a significantly higher titre to MDA-LDL (2.67 vs 2.06, p = 0.003). Cases also had a greater proportion of smokers (37% vs 3%), higher LDL cholesterol (4.2 mmol/l vs 3.6 mmol/l), and higher serum copper concentration (1.14 mg/l vs 1.04 mg/l). Even after adjusting for these variables and the severity of baseline atherosclerosis, the difference in antibody titre remained significant in a multifactorial logistic model (p = 0.031). Thus, the titre of autoantibodies to MDA-LDL was an independent predictor of the progression of carotid atherosclerosis in these Finnish men. Our data provide further support for a role of oxidatively modified LDL in atherogenesis.

Most epidemiological and intervention studies in patients with coronary artery disease have focused on men, the assumption being that such data can be extrapolated to women. However, there is little evidence to support this belief. We have completed a fifteen-year follow-up of 15,399 adults, including 8262 women, who lived in Renfrew and Paisley and were aged 45-64 years when screened between 1972 and 1976. We identified 490 deaths from coronary heart disease (CHD) in women and 878 in men. Women were more likely to have high cholesterol, to be obese, and to come from lower social classes than men, but they smoked less and had similar blood pressures. The relative risk--top to bottom quintile (95% Cl)--of cholesterol for coronary death after adjustment for all other risk markers was slightly greater in women (1.77 [1.45,2.16]) than in men (1.56 [1.32, 1.85]), but absolute and attributable risk were lower. Thus, women in the top quintile for cholesterol had lower coronary mortality (6.1 deaths per thousand patient years) than men in the bottom quintile (6.8 deaths per thousand patient years). Moreover, it was estimated that there would have been only 103 (21%) fewer CHD deaths in women, yet 211 (24%) fewer in men, if mortality had been the same for women and men in the lowest quintiles of cholesterol. Trends showing similar relative risks in these women, but lower absolute and attributable risks than in men, were present for smoking, diastolic blood pressure, and social class. There was no relation between obesity and coronary death after adjustment for other risks. Our results suggest that some other factors protect women against CHD. The potential for women to reduce their risk of CHD by changes in lifestyle may be less than for men.

Prevalence of lymphoproliferative disorders is increased in populations with various chemical exposures, including organophosphorus compounds. Lymphomas are also more common in individuals with a substantially decreased monocyte esterase activity. Organophosphorus compounds inhibit esterases associated with monocytes, natural killer (NK) cells, lymphokine-activated killer (LAK) cells, and cytotoxic T lymphocytes, and these inhibitory effects impair immune surveillance and cytotoxic functions mediated by such cells. Lymphoma development is also associated with Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6) infections, which are regulated by cytotoxic immune responses mediated by monocytes, T cells, and NK cells. My hypothesis is that lymphomagenesis is a multistep process, and the absence or inhibition of monocyte esterase and perhaps other immune cell esterases alters esterase-dependent detoxification of a factor critical for the early steps of oncogenesis. Also, such an enzyme deficit might impair the processes that regulate the dissemination and limit the total burden of pathogens such as the lymphoma-associated herpesviruses. An added risk to any viral-mediated lymphoproliferation might be an organophosphorus-induced oncogenic genetic change.

In the USA, Kaposi's sarcoma associated with the acquired immunodeficiency syndrome (AIDS-KS) is ten times more common in homosexual or bisexual men than in heterosexual men with AIDS. One explanation for this finding is that AIDS-KS may be caused by an infectious agent. Because there is a high incidence of human papillomavirus (HPV) infection, especially HPV-16, in homosexual men, we have sought HPV DNA sequences in Kaposi's sarcoma. We used the polymerase chain reaction with a primer pair specific for the highly conserved E6 region of HPV-16 to detect HPV-16 homologous DNA fragments in tumour tissues from 97 patients with KS and in KS-derived cell cultures. HPV DNA sequences were found in 11 of 69 KS skin tumours from homosexual men with AIDS-KS, in 3 of 11 KS biopsy specimens from homosexual men who had no clinical or laboratory evidence of HIV-infection, and in 5 of 17 KS skin lesions from HIV-1-negative elderly men and women with classic KS. The same primer pair amplified HPV-16 homologous fragments from two different continuous cell cultures derived from pleural effusion fluid of patients with pulmonary AIDS-KS and two continuous cell cultures derived from KS skin lesions. The findings suggest that HPV-16-related DNA sequences are associated with different forms of KS and may have a role in the pathogenesis of this neoplasm.