We examined the relations between bronchial reactivity, baseline FEV,, and annual decline of height corrected FEV, (A FEV,/ht3) over 7-5 years in 227 men (117 smokers, 71 ex-smokers, and 39 non-smokers). Men with a clinical diagnosis of asthma or receiving bronchodilator treatment were excluded. Bronchial reactivity was determined as the provocation concentration (PC20) of inhaled histamine sufficient to reduce FEV, by 20%; subjects were divided into reactors (PC2, -16 mg/ml) and non-reactors (PC2, >16 mg/ml). Thirty per cent of smokers, 24% of ex-smokers, and 5% of non-smokers were reactors. When smokers who were reactors were compared with non-reactors, the reactors showed a lower baseline FEV, as percentage predicted in 1981-2 (85% v 108%), and a faster AFEV,/ht3 (14.1 v 9-2 ml/y/m3). Baseline FEV, correlated with PC20 in both smokers (rs = 0-51) and ex-smokers (r, = 0.61), and all 15 subjects with an FEV, under 80% of the predicted value were reactors. In ex-smokers AFEV,/ht3 was similar in reactors and non-reactors (m 9-0 v 7-4 mL/y/m3), despite significant differences in baseline FEV,. When analysis was confined to men with a baseline FEV, over 80% predicted, the prevalence of reactors was significantly increased among smokers and slightly increased among ex-smokers compared with non-smokers, though the mean FEV, was higher in the non-smokers. Bronchial reactivity was not increased in smokers aged 35 years or less. In smokers AFEV,/ht3 was faster in those with a personal history of allergy (usually allergic rhinitis), but was not related to a family history of allergic disease, total serum immunoglobulin E level, absolute blood eosinophil count, or skinprick test score. AFEV,/ht3 was also faster in all subjects taking beta blocker drugs. Thus increased bronchial reactivity was associated with accelerated decline of FEV, in smokers. Although the association could be a consequence of a lower baseline FEV,, a trend towards increased reactivity was found in smokers with normal baseline FEV, and AFEV,/ ht3 was dissociated from increased reactivity in ex-smokers. These findings are compatible with the " Dutch hypothesis," but the association between allergic features and accelerated AFEV,/ht3 was relatively weak, and increased reactivity may follow rather than precede the onset of smoking.An overall relationship between cigarette smoking and the development of chronic airflow obstruction has been established.' Nevertheless, there is a very wide range of susceptibility to progressive airflow obstruction among smokers, the cause of which is unknown. More than 20 years ago Dutch research workers2 proposed that smokers with chronic and largely irreversible airflow obstruction shared with

SUMMARYEffective primary prevention of congenital toxoplasmosis requires up to date information on locally relevant risk factors for infection in pregnant women. In Naples, risk factors for toxoplasma infection were compared in recently infected women (as assessed by detection of specific IgM in serum) and susceptible, IgG negative women. Recent infection was strongly associated with frequency of consumption of cured pork and raw meat. Eating cured pork or raw meat at least once a month increased the risk of toxoplasma infection threefold.This simple study design for determining locally relevant sources of toxoplasma infection is the first report of cured pork as a risk factor for infection. Further research is required to determine cyst viability in cured pork products. Our findings suggest that in southern Italy, cured pork and raw meat should be avoided by susceptible pregnant women.

We conducted a multicenter, prospective study of the risk factors, natural history, and outcome of fluconazole-refractory mucosal candidiasis (FRMC) in 832 persons with advanced human immunodeficiency virus (HIV) infection (median CD4 cell count, 14/mm3) during 1994-1996. FRMC was defined as mucosal candidiasis that failed to resolve despite 14 days of therapy with daily doses (> or =200 mg) of fluconazole. Thirty-six persons (4.3%) had FRMC (35, oral; 1, esophageal), for an incidence of 4.2 per 100 person-years (859.7 total years of follow-up). In a multivariate model, the use of trimethoprim-sulfamethoxazole within 6 months of enrollment (relative risk [RR], 2.39; P=.04) and the use of fluconazole daily or every other day (RR, 5.64; P=.004) were significantly associated with the development of FRMC. The median survival after the development of FRMC was 32.6 weeks. In conclusion, the annual incidence of FRMC was <5%. Refractory candidiasis was a poor prognostic indicator. Daily or every-other-day use of fluconazole was associated with the development of refractory infection.

Cytomegalovirus (CMV) disease is a common complication of advanced human immunodeficiency virus (HIV) infection. Administration of oral valaciclovir, a valine ester of acyclovir, achieves sufficient plasma acyclovir levels to inhibit many clinical isolates. Acyclovir has been associated with enhanced survival in AIDS but not with CMV disease prevention. CMV-seropositive patients (1227) with CD4 cell counts <100/mm3 were enrolled in a randomized, double-blind trial. Valaciclovir, 8 g/day, was compared with acyclovir, 3.2 or 0.8 g/day, for CMV prevention; all three arms were compared for survival. The confirmed CMV disease rate was 11.7% among valaciclovir recipients and 17.5% in the pooled acyclovir arms, a 33% reduction in risk. Time to confirmed CMV disease was significantly longer for the valaciclovir group (P = .03). A trend toward earlier mortality for valaciclovir recipients was seen (P = .06). Toxicity and earlier medication discontinuation were more common in this group. Valaciclovir significantly reduces the risk of CMV disease. Further exploration of a better-tolerated dose is warranted.