Sputum cytological atypia as a predictor of incident lung cancer in a cohort of heavy smokers with airflow obstruction.

Individuals with cytological atypia in sputum may be at increased risk for lung cancer. We conducted a longitudinal analysis of the association between lung cancer incidence and cytological atypia in sputum samples collected prospectively from an ongoing cohort of adults at high risk for lung cancer. Cohort members had a smoking history of > or = 30 pack-years and chronic obstructive pulmonary disease documented by pulmonary airflow testing. Sputum samples collected at baseline and periodically thereafter were examined by standard cytological methods. From the cohort of 2,006 people, there were 83 incident lung cancers over 4,469 person-years of observation. At baseline, the association between personal and behavioral characteristics, and sputum cytological atypia was assessed by multiple logistic regression. The association between sputum cytological atypia and incident lung cancer was then assessed by hazard ratios using proportional hazards regression analysis, adjusting for potential confounding factors. Cytological atypia graded as moderate or worse was associated with continuing cigarette smoking (adjusted odds ratio, 2.5; 95% confidence interval, 1.5-4.1), and with lower levels of intake of fruits and vegetables (P for trend = 0.04). Atypia was not associated with several other factors, including the degree of airflow obstruction, the use of vitamin supplements, nonsteroidal anti-inflammatory drugs, or metered-dose steroid inhalers. Incident lung cancer was increased among those with moderate or worse cytological atypia (adjusted hazards ratio, 2.8; 95% confidence interval, 1.4-5.5). This association was not confounded by other risk factors. We conclude that in this high-risk cohort, cytological atypia is associated with continuing smoking and low intake of fruits and vegetables, but that independent of these and other factors, the risk of incident lung cancer is increased among those with moderate or worse grades of cytological atypia in their sputum.     

Clinical Classification as a Guide to Treatment of Sinusitis in Children

Evaluation of all 153 children undergoing CT scan of the paranasal sinuses for recalcitrant sinusitis symptoms between January 1988 and July 1992 was performed. Clinical categorization into groups of patients presenting with chronic sinusitis (CS) and recurrent acute sinusitis (RAS) was based upon pattern of disease and presentation. Clinical symptoms and signs, radiological examination, treatment, and outcome were compared between these distinct clinical groups. Eighty-two (55%) children were categorized as RAS and 68 (45%) as CS. Children with CS presented more frequently with a persistent cough, purulent nasal discharge, immune deficiency, and more severe mucosal disease on CT than children with RAS. Medical therapy successfully controlled the symptoms of sinusitis in 79 (96%) with RAS versus 27 (40%) with CS. Surgery was performed in 44 children: 3 (3.6%) with RAS versus 41 (60%) with CS, p<0.01. At a mean follow-up of 2.0 years, >80% of all the children were either asymptomatic or improved regardless of treatment modality. These data support the use of clinical classification as a guide to medical versus surgical therapy in children with sinusitis.     

The association between women’s health information use and health care visits

OBJECTIVE: To determine the effect of the type of information sources used on health services use. METHODS: Population-based random-digit dialing survey of 498 women, between December 1999 and January 2000, on use of health information sources and health visits. RESULTS: After adjustment for sociodemographic and medical factors, use of print health media and computer-based resources was associated with 1.9 and 1.6 more visits, respectively compared to non-use (Regression coefficients 1.9; [95% confidence interval {CI} 0.1, 3.7] and 1.6; [95% CI 0.3, 3.0]). CONCLUSIONS: Print health media and computer-based sources are associated with a higher number of health care visits.     

Prenatal disruption of neocortical development alters prefrontal cortical neuron responses to dopamine in adult rats.

A growing body of evidence suggests that structural changes in the cortex may disrupt dopaminergic transmission in circuits involving the prefrontal cortex (PFC) and may contribute to the etiology of schizophrenia. In this study, we utilize a rodent model of neonatal disruption of cortical development using prenatal administration of the mitotoxin methylazoxymethanol acetate (MAM). Using intracellular recordings in vivo, we compare the physiology of prefrontal cortical neurons and their responses to topical administration of dopamine (DA) in intact animals and adult rats treated prenatally with MAM. Topical administration of DA hyperpolarized the membrane potential (MP) and decreased the firing rate of neurons recorded in deep layers of the PFC in intact animals. Furthermore, electrical stimulation of the VTA evoked fast onset epsps or long-lasting depolarizations in PFC neurons. In comparison, PFC neurons recorded in MAM-treated animals had significantly faster baseline firing rates. Moreover, topical administration of DA did not affect the MP or firing rate of the neurons in MAM-treated animals. However, MAM-treated animals exhibited an increase in the percentage of neurons responding with long-lasting depolarizations to stimulation of the VTA. The results of this study indicate that PFC neurons in the MAM-treated rats are not responsive to DA administered superficially, while at the same time exhibit greater responsiveness to VTA stimulation. These results are consistent with a rewiring of the corticolimbic system in response to neurodevelopmental insults.     

Adult ovary transfer counteracts the callosal enlargement resulting from prepubertal ovariectomy

The rat corpus callosum (CC) is larger in males than females, and is sensitive to hormone manipulations during development. Previous research found that, in rats, CC sensitivity to testosterone ended by postnatal day 8 (P8). In contrast, more recent findings demonstrated that CC responsivity to ovarian hormones continued at least through P70. The current experiment extends these findings by showing that the female callosum is still sensitive to ovarian hormones as late as P130, well into adulthood.     

Polymorphisms and circulating levels in the insulin-like growth factor system and risk of breast cancer: a systematic review.

We reviewed all English-language articles on associations among circulating levels of the insulin-like growth factors (IGF) and their binding proteins (IGFBP), polymorphisms in their genes, and breast cancer risk. In premenopausal women, five of eight IGF-I studies and four of six IGFBP-3 studies of circulating levels found that women in the highest quantile had more than twice the risk of developing breast cancer of those in the lowest, although in some this effect was only apparent at young ages. In postmenopausal women, however, there was no consistent effect. A simple sequence length polymorphism 1 kb 5' to IGF-I was examined in relation to circulating levels of IGF-I (12 studies) or breast cancer risk (4 studies), but there was no convincing evidence of any effect. For an A/C polymorphism 5' to IGFBP-3, all three studies were consistent with a modest effect on circulating levels, but no evidence of a direct effect on breast cancer risk was seen in the only relevant study. Variation within the reference range of IGF-I and IGFBP-3 may confer only modest increases in breast cancer risk, and any single polymorphism may only account for a small proportion of that variation. Nevertheless, population attributable fractions for high circulating levels of IGF-I and IGFBP-3 and for common genetic variants could be substantial. Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely.     

Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International Lymphoma Epidemiology Consortium (interlymph).

BACKGROUND: The International Lymphoma Epidemiology Consortium (InterLymph) provides an opportunity to analyze the relationship between cigarette smoking and non-Hodgkin lymphoma with sufficient statistical power to consider non-Hodgkin lymphoma subtype. The results from previous studies of this relationship have been inconsistent, likely due to the small sample sizes that arose from stratification by disease subtype. To clarify the role of cigarette smoking in the etiology of non-Hodgkin lymphoma, we conducted a pooled analysis of original patient data from nine case-control studies of non-Hodgkin lymphoma conducted in the United States, Europe, and Australia. METHODS: Original data were obtained from each study and uniformly coded. Risk estimates from fixed-effects and two-stage random-effects models were compared to determine the impact of interstudy heterogeneity. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from unconditional logistic regression models, controlling for study center, age, sex, and race. RESULTS: In our pooled study population of 6,594 cases and 8,892 controls, smoking was associated with slightly increased risk estimates (OR, 1.07; 95% CI, 1.00-1.15). Stratification by non-Hodgkin lymphoma subtype revealed that the most consistent association between cigarette smoking and non-Hodgkin lymphoma was observed among follicular lymphomas (n = 1452). Compared with nonsmokers, current smokers had a higher OR for follicular lymphoma (1.31; 95% CI, 1.12-1.52) than former smokers (1.06; 95% CI, 0.93-1.22). Current heavy smoking (> or = 36 pack-years) was associated with a 45% increased OR for follicular lymphoma (1.45; 95% CI, 1.15-1.82) compared with nonsmokers. CONCLUSIONS: Cigarette smoking may increase the risk of developing follicular lymphoma but does not seem to affect risk of the other non-Hodgkin lymphoma subtypes we examined. Future research is needed to determine the biological mechanism responsible for our subtype-specific results.     

Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area.

Pancreatic cancer is one of the most devastating and rapidly fatal cancers, yet little is known about the primary cause and prevention of this disease. We conducted a population-based case-control study to investigate the association between vegetables and fruits and pancreatic cancer. Between 1995 and 1999, 532 cases and 1,701 age- and sex-matched controls completed direct interviews using a semiquantitative food-frequency questionnaire. No proxy interviews were conducted. We observed inverse associations between consumption of total and specific vegetables and fruits and the risk of pancreatic cancer. The odds ratio and 95% confidence interval for the highest versus the lowest quartile of total vegetable intake was 0.45 (0.32-0.62), trend P < 0.0001; and for total fruits and fruit juice was 0.72 (0.54-0.98), trend P = 0.06. Odds ratios and 95% confidence intervals for the highest versus the lowest quartile of specific vegetables and fruits were: 0.63 (0.47-0.83) for dark leafy vegetables, 0.76 (0.56-1.0) for cruciferous vegetables, 0.59 (0.43-0.81) for yellow vegetables, 0.56 (0.41-0.76) for carrots, 0.51 (0.38-0.70) for beans, 0.46 (0.33-0.63) for onions and garlic, and 0.78 (0.58-1.0) for citrus fruits and juice. Compared with less than five servings per day of total vegetables and fruits combined, the risk of pancreatic cancer was 0.49 (0.36-0.68) for more than nine servings per day. These results suggest that increasing vegetable and fruit consumption, already recommended for the prevention of several other chronic diseases, may impart some protection against developing pancreatic cancer.