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The NMC analyses were used to study medium-scale waves during three Southern Hemisphere (SH) summers. The SH summer medium-scale waves are observed to exhibit remarkably regular eastward phase progression, and wave maxima can often be traced continuously around the globe. Frequent downstream development of existing wave patterns is observed. The medium-scale waves at times appear to be longitudinally localized features; at other times they resemble truly global-scale models. The time-mean wave structure is found to be consistent with basic-state propagation characteristics and the conservation of wave activity. There is a tendency for background wind structure to restrict wave propagation. From energetics studies it is found that wave-zonal-mean exchange is a valid concept for describing the SH summer circulation, and that the flow vacillated between periods of highly perturbed and zonally symmetric states. The medium-scale waves result from nonlinear baroclinic instabilities, and exhibit a well-defined life cycle of baroclinic growth, maturity, and barotropic decay.

Allergy, auto immunity and cancer are becoming more prevalent in the developed world. One explanation might be that the immune system required to protect us from such problems is being inadequately trained, perhaps due to our increased separation from the environment which has shaped our mutating genes since we emerged from the primaeval ooze. Those infections which were the essential primers of our immunity are being prevented and action is needed to refocus the immune response without exposing us to the diseases of the past. In this paper we assess our place in relation to the environment and consider ways in which the situation can be redressed. There are considerable similarities between the immune system and human consciousness. Both enter the world in considerable ignorance of the events awaiting them, yet with the genetic ability, endowed by millennia of selection and evolution, to experience the world, to interpret and act on the experiences and to retain memory of the experiences. In both systems, maternal influences and early environmental encounters have profound effects on determining the patterns of subsequent responses. Ideally the ‘learned’ responses will benefit or protect the individual but inappropriate responses may lead to self damage. As the environment has altered irrevocably, attention must be paid to regulating the balance of immunological responsiveness to that expected of the normal immunological learning process. This should be possible by novel vaccination strategies.

This study compares the horizontal resolution of solar backscatter ultraviolet 2 (SBUV2) total ozone (Ω) fields with those from the new NASA earth probe (EP) and Advanced Earth Observing Satellite (ADEOS) total ozone mapping spectrometer (TOMS) side-scanning photometers. The latter instruments provide high resolution, easily resolving the medium-scale waves (4–7 wavelengths around the Earth at a fixed latitude) that dominate day-to-day midlatitude Ω fluctuations. In contrast, SBUV2 instruments do not, since these devices measure only at nadir (straight downward), yielding ∼14 measurements daily at a given latitude. This method has consequences not only for global monitoring of Ω and ultraviolet B (UVB, 290–320 nm), but also for short-timescale Ω and UVB predictions in summer because timescales of a few days are coupled to medium horizontal scales (several thousand kilometers) by baroclinic waves that typically force the observed Ω variations. We use a simple Ω prediction model to test the use of Ω fields from TOMS and SBUV instruments and show that the higher zonal resolution from side-scanning TOMS instruments results in sizeable reductions in Ω prediction errors, whereas predictions using SBUV2 Ω are no better than persistence (where tomorrow's Ω is taken to be today's) in the biologically important summer months. Daily variabilities (equivalent to errors in 24-hour persistence forecasting of Ω) in high-resolution TOMS midlatitude ozone during summer are shown to sometimes exceed 50 Dobson units, producing daily changes of 20% or greater in computed ground-level clear-sky UV index. This study demonstrates that even these large daily changes in measured or predicted clear-sky UV are usually smaller than daily UV changes associated with transient clouds. While surface UVB variability is dominated by local cloudiness variations, Ω forecasts can enhance UVB prediction in relatively cloud free regions such as the U.S. desert southwest and in stagnant high-pressure regimes that can persist for 1–2 weeks in summer. Furthermore, as weather forecast models increase in accuracy of forecasted cloudiness, accurate predictions will allow more accurate UVB forecasts for cloud free regions, the locations where they are most needed. Results from the present paper show, however, that high-resolution TOMS-like side-scanning Ω measurements are required for ozone and UVB monitoring and prediction, rather than SBUV-type nadir observations.

A series of segmented polyurethanes containing 60 wt° of hard segments (HS) was prepared from MDI (4,4′-diphenylmethane diisocyanate) ethylene glycol and mixtures of a polyoxyethylene end-capped polyoxypropylene triol and a polyoxyethylene end-capped polyoxypropylene diol. The effects of the content of polyether diol in polyether polyols on phase separation and properties was investigated by dynamic mechanical analysis (DMA), differential scanning calorimetry (DSC) and investigation of tensile properties. The DSC and DMA results indicate that the polyurethane derived from only polyether triol exhibits obvious phase separation and that the HS is immiscible with the SS, but that the HS is compatible with the HS for the polyurethane derived from polyether diol. As the content of polyether diol increases, the compatibility between HS and SS increases. As the content of polyether diol increases, the tensile strength. elongation. toughness and tear resistance of the polyurethanes increases. but their moduli decrease. The modulus-temperature dependence in the temperature region of −30 to 65 °C increases as the polyether diol content increases.

Objective To investigate whether, in the absence of galactosemia, relatively high intestinal lactase activity or low activity of an enzyme involved in galactose catabolism reduces fertility, as it does in the presence of galactosemia. Design Retrospective cohort study. Setting Healthy women selected from the community. Patients Fifty-three married women. Intervention Urinary galactose after an oral lactose challenge (a measure of intestinal lactase activity), erythrocyte galactose-1-phosphate uridyltransferase (transferase) activity, and transferase polymorphisms by isoelectric focusing. Main Outcome Measure Pregnancy rate (number of pregnancies divided by number of months at risk) in the 12months after stopping use of birth control to become pregnant. Results Relatively high urinary galactose was not related to a decreased rate of pregnancy during the first 12months (≥24.6 compared with ≤14.3mg: relative risk [RR] = 1.9; 95% confidence interval [CI] = 0.86 to 4.0). Relatively high transferase activity was not related to an increased rate of pregnancy (≥19.5 compared with ≤17.2 μ mol/h per g hemoglobin: RR=1.1; 95% CI=0.56 to 2.4). Low-activity transferase polymorphisms were not related to a decreased rate (RR = 1.2; 95% CI=0.58 to 2.5). Conclusion Our study does not support the hypothesis that the biologic variation in galactose metabolism that exists in the general population influences infertility.

BACKGROUND: T cell response to mycobacterial antigens may be directed against those antigens common to all mycobacteria (group i), those restricted to slow (group ii) or fast growers (group iii), or those which are species- or subspecies-specific (group iv). These responses were assessed by skin testing patients infected with the human immunodeficiency virus (HIV) and healthy controls with reagents derived from different strains of mycobacteria. METHODS: Skin test responses to new tuberculins prepared from Mycobacterium tuberculosis, M avium serotypes 4 and 8, and either M intracellulare or M flavescens antigens were evaluated prospectively in 51 HIV infected patients and 67 healthy controls. RESULTS: Assessment of induration at 72 hours showed absence of skin test response to common mycobacterial antigens in all 27 HIV positive patients with CD4 counts of > or = 400/mm3 (range 400-1594, median 540) compared with 27% reactivity in controls; complete anergy was demonstrated in 24 patients with CD4 counts of < 400/mm3. By contrast, no difference in species or subspecies-specific responses was found between healthy controls and HIV positive patients with CD4 counts of > or = 400/mm3. CONCLUSIONS: Subsets of CD4+ T helper cells are instrumental in determining the balance between cell-mediated and humoral immunity. One T helper subset (TH1) produces cytokines that increase cellular immunity and is stimulated by group i common mycobacterial antigens. Lack of this response, but preservation of responses to species-specific antigens while CD4 counts are near normal, may indicate an early failing of TH1 immunity and explain the increased susceptibility of HIV positive patients to mycobacterial infection early on in the evolution of their HIV infection.

Peripheral blood mononuclear cells taken from 32 patients with Rheumatoid Arthritis (RA) receiving neither steroids nor methotrexate and 34 healthy controls were examined for lymphoproliferation in the presence of ultrasonic extracts of 14 different mycobacterial species or serotypes, of an extract of Candida albicans and of 2 mitogens. Additionally, cells were incubated for 96 hours alone, or with Mycobacterium tuberculosis (M.tb) sonicate or Concanavalin-A (Con-A), and supernatants were tested for a range of cytokines. Lymphocytes of rheumatoid patients were less reactive than controls to all the mycobacterial preparations, but no different in their responses to mitogens. Stimulation of patients' cells with M.tb sonicate induced significantly less interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) but more transforming growth factor- beta (TGF-beta) than controls. Even stimulation with Con-A induced much less IFN-gamma in patient's cells than in those of controls. The combination of reduced responses to the mycobacterial reagents and reduced stimulation of type 1 cytokines by the sonicate of M.tb, suggests reduced responsiveness to group i, common mycobacterial antigens. Such findings need not indicate involvement of mycobacteria specifically in the disease aetiology, but provide novel information on the immunopathological abnormalities, which may explain the reported increased susceptibility to mycobacteria of RA patients.

Summary Background Through its powerful immunoregulatory effects, infection with atypical mycobacteria may exert a protective effect on the development of childhood allergic disease. Objective To examine the relationship between childhood atopy or allergic disease and previous infection with four species of atypical mycobacteria. Methods Eight hundred and six children aged 8–18 years and living in rural Crete – most of whom had had previous BCG immunization – underwent skin prick testing with 10 aeroallergens; their parents completed a standardized questionnaire relating to allergic disease. No less than 8 weeks later each child underwent intradermal skin tests with 0.1 mL solutions of four selected mycobacterial reagents (Aviumin C, Gordonin, Chelonin and Ranin I). Results Twenty-three percent of children were atopic on skin prick testing; far fewer had symptoms of asthma (5%) or hayfever in conjunction with a positive prick test to pollens (2%). Eighty percent of children had positive skin responses to one or more mycobacterial species. Among all children – and those with a BCG scar – there was no association between atopy or allergic symptoms and mycobacterial skin responses; among the few children without a BCG scar however those with positive mycobacterial responses were less likely to be atopic or to report allergic symptoms; these differences were not statistically significant. Conclusions Our findings, in a population of BCG-immunized children, do not lend support to the suggestion that infection with atypical mycobacteria is protective against childhood allergic disease.

Conversion of partial- to full-thickness injuries, even after the burning has stopped, remains a significant clinical problem. We developed a rat model with a wide range of burn depths to study this phenomenon by microvascular assessment. Fifty-four male Sprague-Dawley rats weighing 460 g on average were studied. Real-time tissue monitoring of pH, paCO2, and paO2 was achieved by placement of a continuous blood gas monitor transducer in the aorta. Ten, 2-cm x 2-cm burns were created on each animal with milled aluminum templates (100 degrees C) with varying contact times. Conversion of burn depth in these wounds was documented by serial laser Doppler imager scanning over a 5-hour period. Animals received Ringer's lactate resuscitation at 0, 2, 4, 6, and 8 ml/kg/%burn. Serial laser Doppler scanning directly demonstrated progressive loss of perfusion to partial-thickness burns dependent upon the amount of fluid resuscitation. Conversion of partial- to full-thickness burns in this rat model (documented by laser Doppler microvascular assessment) was dependent upon how the animals were resuscitated.

Incidence rates for adenocarcinoma of the esophagus and gastric cardia have been rising rapidly. We examined nutrient intake as a risk factor for esophageal and gastric cancers in a population-based case-control study in Connecticut, New Jersey, and western Washington state. Interviews were completed for cases with histologically confirmed esophageal adenocarcinoma (n = 282), adenocarcinoma of the gastric cardia (n = 255), esophageal squamous cell carcinoma (n = 206), and noncardia gastric adenocarcinoma (n = 352), along with population controls (n = 687). Associations between nutrient intake and risk of cancer were estimated by adjusted odds ratios (ORs), comparing the 75th versus the 25th percentile of intake. The following nutrients were significantly inversely associated with risk of all four tumor types: fiber, beta-carotene, folate, and vitamins C and B6. In contrast, dietary cholesterol, animal protein, and vitamin B12 were significantly positively associated with risk of all four tumor types. Dietary fat [OR, 2.18; 95% confidence interval (CI), 1.27-3.76] was significantly associated with risk of esophageal adenocarcinoma only. Dietary nitrite (OR, 1.65; 95% CI, 1.26-2.16) was associated with noncardia gastric cancer only. Vitamin C supplement use was associated with a significantly lower risk for noncardia gastric cancer (OR, 0.60; 95% CI, 0.41-0.88). Higher intake of nutrients found primarily in plant-based foods was associated with a reduced risk of adenocarcinomas of the esophagus and gastric cardia, whereas higher intake of nutrients found primarily in foods of animal origin was associated with an increased risk.

Hereditary prostate cancer is an etiologically heterogeneous disease with six susceptibility loci mapped to date. We aimed to describe a collection of high-risk prostate cancer families and assess linkage to multiple markers at four loci: HPC1 (1q24-25), PCaP (1q42.2-43), HPCX (Xq27-28), and CAPB (1p36).Medical record data on 505 affected men in 149 multiply-affected prostate cancer families were reviewed, and correlations of clinical traits within each family were calculated. Logarithm of odds (LOD) score and nonparametric (NPL) linkage analyses were performed; white families were stratified by age of diagnosis, grade and stage of disease, and evidence of linkage to the other loci to increase genetic homogeneity.Age at diagnosis was the most correlated clinical trait within families. A maximum NPL score of 2.61 (P = 0.007) appeared to confirm HPC1 linkage for families that had a prevalence of high-grade or advanced-stage prostate cancer and which were not likely to be linked to PCaP, HPCX, or CAPB. Because the NPL scores improved when families more likely to be linked to the other loci were excluded, HPC1 may act independently of the other loci. The relationship of HPC1 and aggressive disease was strongest in families with median age at diagnosisor =65 years (NPL, 3.48; P = 0.0008).The current results suggest that HPC1 linkage may be most common among families with more severe prostate cancer. Stratification by clinical characteristics may be a useful tool in prostate cancer linkage analyses and may increase our understanding of hereditary prostate cancer.

To conduct timely epidemiologic investigations of molecular/genetic markers that may contribute to the development of prostate, lung, colorectal, or other cancers within the Selenium and Vitamin E Cancer Prevention Trial (SELECT), and to evaluate interactions between these markers and the study interventions.The epidemiologic studies within SELECT will be based on 32,400 men aged 55 years or older (age 50 or older for the African-American men) enrolled into an intergroup, randomized, placebo-controlled, double-blind, phase III prevention trial of supplemental selenium and vitamin E developed and funded by the National Cancer Institute, and coordinated by the Southwest Oncology Group. During the 12-year study period approximately 1500-2000 cases of prostate cancer, 800 lung cancers, and 500 colon cancers are estimated to be diagnosed, based on data from the ongoing Prostate Cancer Prevention Trial of finasteride. A modified fasting blood sample will be processed to collect plasma for analysis of micronutrients, hormones, cytokines, and other proteins. Buffy-coat derived white blood cells collected at baseline will be used for isolation of DNA and establishment of immortalized cell lines. Red blood cells will be stored for analysis of hemoglobin adducts and other components.Specific results anticipated from these molecular studies will provide information on factors hypothesized to contribute to prostate cancer risk and that may modify the efficacy of either trial supplement, including: steroid sex hormones and several polymorphic genes that encode proteins affecting androgenic stimulation of the prostate, including the androgen receptor, steroid 5alpha-reductase type II, CYP17, and beta-hydroxysteroid dehydrogenase; polymorphisms of DNA repair genes and carcinogen metabolism genes, including those involved in the activation of chemical carcinogens to reactive intermediates (e.g., CYP1A1) or the detoxification of reactive intermediates (e.g., glutathione S-transferase M1); DNA and protein adducts; and insulin-like growth factors and leptin.SELECT offers an excellent opportunity to conduct molecular epidemiologic investigations to assess gene-environment interactions and their role in prostate, lung, and colon carcinogenesis.

Parallel to its established causal association with both infectious mononucleosis (IM) and young adulthood Hodgkin disease (YAHD), we propose a hypothesis that "delayed" primary EBV infection (i.e., primary infection occurring during adolescence or adulthood) is associated with elevated breast cancer risk. We evaluated this hypothesis with two investigations, one descriptive and the other analytic. The descriptive study used international/United States cancer registry data to assess the association between incidence rates of breast cancer and those of YAHD. The incidence rates of the seemingly unrelated neoplasms were strongly correlated (correlation coefficients of 0.74 and 0.88 for international and United States data, respectively; these were higher than the correlation coefficients of YAHD with two other cancers that we considered). Populations with higher incidence rates corresponded to those with higher likelihood of delayed primary EBV infection. The analytical study was based on a population-based case-control study of breast cancer in middle-aged women. Age-adjusted odds ratios of breast cancer in women who reported a history of IM, relative to women who did not, increased monotonically from 0.55 [95% confidence interval (CI), 0.05-6.17] for women with 0-9 years of age at IM onset to 2.67 (CI, 1.04-6.89) for women withor =25 years of age at IM onset (P = 0.016). An older age at tonsillectomy, another surrogate of delayed EBV exposure, was also associated with increased risk of breast cancer: odds ratios, 0.92 (CI, 0.57-1.48) and 1.76 (CI, 1.15-2.69) for women with tonsillectomy at 0-4 years of age andor =15 years of age, respectively (P = 0.018). Adjusting for additional potential confounders did not modify the associations appreciably. The implications of the findings and a potential biological mechanism are presented.

To investigate Mycobacterium vaccae immunotherapy in the treatment of human tuberculosis and to assess longer-term outcomes following treatment for tuberculosis patients, a double-blind placebo-controlled Phase-2 clinical trial was set up in the Mseleni and Manguzi health wards in north-eastern KwaZulu, South Africa. In 1991-93, 204 patients admitted with clinical tuberculosis to the 2 hospitals were allocated to receive single intradermal doses of 0.1 mL M. vaccae NCTC 11659 or 0.1 mL tetanus toxoid alongside standard 6-months chemotherapy with rifampicin, isoniazid, pyrazinamide and ethambutol. The main outcome measures were sputum bacteriology culture conversion to negativity, clinical assessment, weight gain, erythrocyte sedimentation rate and chest radiography. Patients were followed-up after 4 years to determine their health status. M. vaccae cases gained weight more quickly during the first 8 weeks compared with 'placebo' patients. Regression analysis found a synergistic relationship between BCG positive scar status and M. vaccae-induced weight gain. No further difference was found between treatment groups. The bacterial conversion rate to negativity at 2 months was much lower than expected (44.8% active, 38.8% placebo). Mortality was considerably higher than expected after treatment (7.1% each group) and after 4 years (25.8% active, 21.0% placebo; death from tuberculosis 14.5% and 16.1%, respectively). Immune sensitization to environmental mycobacteria may explain the geographical variability of M. vaccae efficacy, as occurs with BCG vaccination and occurred with Koch's tuberculins of the late 19th century. Multiple doses of M. vaccae may be more effective. Further work is required to link the ability of M. vaccae to modulate protective cytokine profiles to favourable outcome in clinical studies. The high mortality found in this study suggests urgent reviews of chemotherapy and monitoring of patients are necessary in KwaZulu.

More than 36000 individuals living in rural Malawi were skin tested with antigens derived from 12 different species of environmental mycobacteria. Most were simultaneously tested with RT23 tuberculin, and all were followed up for both tuberculosis and leprosy incidence. Skin test results indicated widespread sensitivity to the environmental antigens, in particular to Mycobacterium scrofulaceum, M. intracellulare and one strain of M. fortuitum. Individuals with evidence of exposure to ‘fast growers’ (i.e. with induration to antigens from fast growers which exceeded their sensitivity to tuberculin), but not those exposed to ‘slow growers’, were at reduced risk of contracting both tuberculosis and leprosy, compared to individuals whose indurations to the environmental antigen were less than that to tuberculin. This evidence for cross protection from natural exposure to certain environmental mycobacteria may explain geographic distributions of mycobacterial disease and has important implications for the mechanisms and measurement of protection by mycobacterial vaccines.

The incidence of esophageal adenocarcinoma has risen rapidly in the past two decades, for unknown reasons. The goal of this analysis was to determine whether gastroesophageal reflux disease (GERD) or the medications used to treat it are associated with an increased risk of esophageal or gastric cancer, using data from a large population-based case-control study.Cases were aged 30-79 years, newly diagnosed with esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261), or non-cardia gastric adenocarcinoma (n = 368) in three areas with population-based tumor registries. Controls (n = 695) were chosen by random digit dialing and from Health Care Financing Administration rosters. Data were collected using an in-person structured interview.History of gastric ulcer was associated with an increased risk of non-cardia gastric adenocarcinoma (OR 2.1, 95% CI 1.4-3.2). Risk of esophageal adenocarcinoma increased with frequency of GERD symptoms; the odds ratio in those reporting daily symptoms was 5.5 (95% CI 3.2-9.3). Ever having used H2 blockers was unassociated with esophageal adenocarcinoma risk (OR 0.9, 95% CI 0.5-1.5). The odds ratio was 1.3 (95% CI 0.6-2.8) in long-term (4 or more years) users, but increased to 2.1 (95% CI 0.8-5.6) when use in the 5 years prior to the interview was disregarded. Risk was also modestly increased among users of antacids. Neither GERD symptoms nor use of H2 blockers or antacids was associated with risk of the other three tumor types.Individuals with long-standing GERD are at increased risk of esophageal adenocarcinoma, whether or not the symptoms are treated with H2 blockers or antacids.

We determine the positive yield of imaging studies performed on men with newly diagnosed prostate cancer.A prospective, population based survey was conducted on 3,690 men with prostate cancer diagnosed between October 1, 1994 and October 31, 1995. Cases were identified by the rapid case ascertainment systems used in 6 geographic regions participating in the Surveillance, Epidemiology and End Results Program. Based on information captured in primary medical record reviews we estimated the positive yield of bone scans, computerized tomography (CT) and magnetic resonance imaging.The positive yield of bone scan and CT was less than 5% and 12%, respectively, for all men with prostate specific antigen (PSA) 4 to 20 ng./ml., and less than 2% and 9%, respectively, for those who also had a Gleason score of 6 or less. Only men with PSA greater than 50 ng./ml. and those with Gleason scores 8 to 10 and PSA greater than 20 ng./ml. had positive yields greater than 10% and 20% for bone scan and CT, respectively.Imaging studies designed to identify metastases and/or extracapsular extension in men with newly diagnosed prostate cancer frequently have a low positive yield. Wide variations exist in the use of imaging studies and are associated with tumor factors, such as Gleason score and serum PSA, and nontumor factors, such as state of residence. More extensive cost-effectiveness analyses are needed to define appropriate guidelines for ordering imaging studies to optimize the positive yield among men with newly diagnosed prostate cancer.

Confirmation of linkage and estimation of the proportion of families who are linked in large independent datasets is essential to understanding the significance of cancer susceptibility genes. We report here on an analysis of 150 high-risk prostate cancer families (2,176 individuals) for potential linkage to the HPC1 prostate cancer susceptibility locus at 1q24-25. This dataset includes 640 affected men with an average age at prostate cancer diagnosis of 66. 8 years (range, 39-94), representing the largest collection of high-risk families analyzed for linkage in this region to date. Linkage to multiple 1q24-25 markers was strongly rejected for the sample as a whole (lod scores at theta = 0 ranged from -30.83 to -18. 42). Assuming heterogeneity, the estimated proportion of families linked (alpha) at HPC1 in the entire dataset was 2.6%, using multipoint analysis. Because locus heterogeneity may lead to false rejection of linkage, data were stratified based on homogeneous subsets. When restricted to 21 Caucasian families with five or more affected family members and mean age at diagnosis= 65 years, the lod scores at theta = 0 remained less than -4.0. These results indicate that the overall portion of hereditary prostate cancer families whose disease is due to inherited variation in HPC1 may be less than originally estimated.

Most studies do not support an association between vasectomy and prostate cancer, but a few have suggested a link. Vasectomy is a common birth control method, and prostate cancer is the most frequently diagnosed solid tumor in men, making this a major public health question. This study was specifically designed to determine whether or not vasectomy is associated with risk of prostate cancer. To examine this issue, we conducted a population-based case-control study in King County, Washington. Interviews were completed with men ages 40-64 years newly diagnosed with prostate cancer between January 1993 and December 1996 who were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry (n = 753) and with comparison men without prostate cancer identified from the same general population (n = 703). The odds ratio (OR) for prostate cancer in relation to vasectomy was assessed. The prevalence of vasectomy was similar in cases (39.4%) and controls (37.7%), resulting in no association (adjusted OR, 1.10; 95% confidence interval, 0.9-1.4). There was no consistent evidence that risk varied by the age at which vasectomy was performed, the time since vasectomy, or the calendar period when the vasectomy was performed. The OR in relation to vasectomy was higher in men with less aggressive prostate cancer. Risk estimates did not differ according to age, race, or family history of prostate cancer. This study suggests that vasectomy is not associated with the risk of developing prostate cancer. It also provides evidence that vasectomized men may be more likely to present with earlier-stage, lower-grade prostate tumors.

This population-based, case-control study in King County, Washington examined supplement use in 697 incident prostate cancer cases (ages 40-64) identified from the Puget Sound Surveillance, Epidemiology and End Results program registry and 666 controls recruited from the same overall population using random-digit dialing sampling. Participants reported their frequency of use of three types of multivitamins and single supplements of vitamins A, C, and E, calcium, iron, and zinc over the 2 years before diagnosis. Logistic regression analyses controlled for age, race, education, family history of prostate cancer, body mass index, number of prostate-specific antigen tests in the previous 5 years, and dietary fat intake. Adjusted odds ratios (95% confidence limits) for the contrast ofor =7/week versus no use were as follows: multivitamins, 0.96 (0.73, 1.26); vitamin A, 0.59 (0.32, 1.06); vitamin C, 0.77 (0.57, 1.04); vitamin E, 0.76 (0.54, 1.08); calcium, 1.04 (0.61, 1.78); iron, 0.50 (0.13, 1.76); and zinc, 0.55 (0.30, 1.00). Odds ratios differed little when cases were stratified by stage of disease at diagnosis or by histopathological grade. There were significant dose-response effects for zinc and ordered dose-response trends for vitamins C and E. Overall, these results suggest that multivitamin use is not associated with prostate cancer risk, but use of individual supplements of zinc, vitamin C, and vitamin E may be protective. Further study is needed to investigate the direct role of these dietary supplements, as well as the role of lifestyle variables associated with supplement use, on prostate cancer risk.

We investigated whether clinical information routinely available in community practice could predict extracapsular extension of clinically localized prostate cancer in men undergoing radical prostatectomy.We examined prostate cancer outcomes in a population based sample of 3,826 patients with primary prostate cancer in 6 regions of the United States covered by the Surveillance, Epidemiology, and End Results program. Stratified and weighted logistic regression was used to identify predictors of and probabilities for extracapsular extension of clinically localized tumors treated with radical prostatectomy.Nearly 47% of men undergoing radical prostatectomy had extraprostatic extension. The strongest predictors were elevated prostate specific antigen (PSA) greater than 20 versus less than 4 ng./ml. (odds ratio 5.88, 95% confidence interval 2.90 to 11.15), Gleason score greater than 8 versus less than 6 (1.73, 1.04 to 2.87) and age greater than 70 versus less than 50 years (1.91, 0.98 to 3.70). Ethnicity and region were not associated with increased risk of extraprostatic extension. A nomogram developed from our model predicts extracapsular extension ranging from 24% in men younger than 50 years with PSA less than 4 ng./ml. and a Gleason score of less than 7 to 85% in those 70 years old or older with PSA greater than 20 ng./ml. and a Gleason score of 8 or more. If prostatectomy were limited to patients with less than 60% probability of extraprostatic extension based on the nomogram, 95% of those with organ confined cancers would undergo definitive surgery and 18% of those with extracapsular extension would be spared the morbidity of surgery.In a population based analysis of prostate cancer practice patterns PSA, Gleason score and age are clinically useful predictors of extracapsular extension. Although extracapsular extension may be an imperfect predictor of cancer outcomes, our nomogram provides more realistic probabilities for extracapsular extension than those based on institutional series.

To evaluate whether heavy cigarette smoking as a teenager or long-term smoking increases breast cancer risk or, alternatively, whether smoking acts as an anti-estrogen and reduces risk.Data from a multi-center, population-based, case-control study among women under age 55 were analyzed.Among women under age 45, there was a modest inverse relation with current (OR = 0.82, 95% CI = 0.67, 1.01) but not past (OR = 0.99, 95% CI = 0.81, 1.21) smoking. Odds ratios were decreased for current smokers who began at an early age (0.59 foror = 15, 95% CI = 0.41, 0.85) or continued for long periods of time (0.70 for21 years, 95% CI = 0.52, 0.94). In subgroup analyses, reduced odds ratios were observed among current smokers who were ever users of oral contraceptives (0.79, 95% CI = 0.63, 0.98), were in the lowest quartile of adult body size (0.53, 95% CI = 0.34, 0.81), or never or infrequently drank alcohol (0.68, 95% CI = 0.47, 0.98). Among women ages 45-54, there was little evidence for an association with smoking.These results suggest that breast cancer risk among women under age 45 may be reduced among current smokers who began smoking at an early age, or long-term smokers, but require confirmation from other studies.

Using data from a case-control study conducted in Group Health Cooperative (GHC) of Puget Sound, we examined the relation between the use of electric blankets or heated water beds and the risk of prostate cancer. Cases were 175 prostate cancer patients ages 40-69 years. Controls were 258 male GHC members frequency matched to cases. The odds ratio (OR) for prostate cancer associated with the use of an electric blanket or heated water bed was 1.4 (95% confidence interval (CI) 0.9-2.2). The risk, however, did not tend to be higher with increasing months per year or years of use. This study did not provide clear evidence on the hypothesized association.

To assess effects on breast cancer risk of exposure to both oral contraceptives and menopausal hormones, an increasingly common exposure.A case-control study of breast cancer among women under the age of 55 years in Atlanta, GA involving 1,031 cases and 919 population controls was conducted.Ever use of oral contraceptives was associated with a relative risk of 1.1 (95% 0.9-1.4), whereas the relative risk for hormone replacement therapy was 0.9 (95% CI 0.7-1.2). Seventeen percent of the cases versus 19% of the population controls reported exposure to both agents, resulting in a relative risk of 1.0 (95% CI 0.7-1.4) relative to those unexposed to either preparation. Although there was little variation in risk associated with joint effects by either age or race, there were statistically nonsignificant elevations in risk for this exposure among women who had experienced a natural menopause (relative risk = 2.0, 95% CI 0.7-5.6), were relatively thin (relative risk = 1.5, 0.8-3.0), or who had a first degree relative with breast cancer (relative risk = 2.0, 0.6-7.0). When joint effects of longer term use of both agents were considered, subjects who reported use of oral contraceptives for 10 or more years and hormone replacement for 3 or more years had a relative risk of 3.2 (95% CI 1.4-7.4) compared with nonusers of either preparation.Although our results must be cautiously interpreted given small numbers within subgroups, they raise concern and emphasize the need for further evaluation on breast cancer risk of the increasingly common exposure to both oral contraceptives and hormone replacement therapy.

A cohort study was conducted to estimate the risk of breast cancer recurrence among women diagnosed with ductal carcinoma in situ (DCIS) and to identify tumor or patient characteristics that influence that risk. A population-based cancer registry was used to identify a cohort of 709 female residents of western Washington who were diagnosed with DCIS between January 1980 and June 1992 and were treated with breast-conserving surgery. Information about breast cancer recurrences, treatment, and several patient characteristics and exposures was obtained from postal questionnaires. Recurrences were confirmed using information from the cancer registry or hospital pathology reports. Approximately 15% of women experienced a recurrence within the first 5 years after diagnosis [95% confidence interval (CI), 12-18%]; 31% had a recurrence within 10 years (95% CI, 24-38%). There was a suggestion that risk was slightly elevated for women with larger tumors (or =1.5 cm) and tumors of comedo subtype. Relative risks (RRs) were elevated for women who were premenopausal at diagnosis of DCIS (RR = 2.3; 95% CI, 1.1-5.0). Women in the upper decile of body mass index were at twice the risk of a recurrence as those women in the lower four deciles (RR = 2.3; 95% CI, 1.1-4.8). There was also a suggestion that women who used menopausal hormones for at least 2 years after their diagnosis of DCIS were at increased risk of recurrence compared to nonusers of menopausal hormones (RR = 1.8; 95% CI, 0.7-5.0). Our results suggest that the risk of recurrence may be related to some tumor characteristics as well as the hormonal milieu of the patient at or after her diagnosis of DCIS. However, larger studies are needed to more clearly document predictors of disease recurrence after DCIS.

To evaluate the prevalence of recreational physical activity in middle-aged women and to identify characteristics predisposing women to an active or sedentary lifestyle.In this population-based survey study of 492 women aged 50-64 years, women were interviewed between 1988 and 1993 regarding their recreational exercise habits, other health habits, and medical history. Women were selected from the general population of western Washington State through random-digit-dialing of telephones. Physical activities in a recent 2-year period were recorded, including specific types, frequency, and duration of each activity.Fewer than half of the women reported doing any regular physical activity and only 27% engaged in any high intensity exercise. Obesity, current cigarette smoking, low income, low education, and some dietary factors were associated with a sedentary lifestyle.These results suggest that only about half of middle-aged women engage in any regular recreational exercise, and that less than 25% follow the National Institutes of Health recommended guidelines for light to moderate exercise for at least 30 min per day, 6 days per week.

Modern vaccinations, fear of germs and obsession with hygiene are depriving the immune system of the information input upon which it is dependent. This fails to maintain the correct cytokine balance and fine-tune T-cell regulation, and may lead to increased incidences of allergies and autoimmune diseases. If humans continue to deprive their immune systems of the input to which evolution has adapted it, it may be necessary to devise ways of replacing it artificially.

Gastric colonization with Helicobacter pylori, especially cagA+ strains, is a risk factor for noncardia gastric adenocarcinoma, but its relationship with gastric cardia adenocarcinoma is unclear. Although incidence rates for noncardia gastric adenocarcinoma have declined steadily, paralleling a decline in H. pylori prevalence, rates for adenocarcinomas of esophagus and gastric cardia have sharply increased in industrialized countries in recent decades. To clarify the role of H. pylori infection in these tumors with divergent incidence trends, we analyzed serum IgG antibodies to H. pylori and to a recombinant fragment of CagA by antigen-specific ELISA among 129 patients newly diagnosed with esophageal/gastric cardia adenocarcinoma, 67 patients with noncardia gastric adenocarcinoma, and 224 population controls. Cancer risks were estimated by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Infection with cagA+ strains was not significantly related to risk for noncardia gastric cancers (OR, 1.4; CI, 0.7-2.8) but was significantly associated with a reduced risk for esophageal/cardia cancers (OR, 0.4; CI, 0.2-0.8). However, there was little association with cagA- strains of H. pylori for either cancer site (OR, 1.0 and 1.1, respectively). These findings suggest that the effects of H. pylori strains on tumor development vary by anatomical site. Further studies are needed to confirm these results and to assess whether the decreasing prevalence of H. pylori, especially cagA+ strains, may be associated with the rising incidence of esophageal/gastric cardia adenocarcinomas in industrialized countries.

Methodologic investigations have addressed selection and recall bias in case-control studies of diet and breast cancer, whereas the effect of disease progression and medical treatment on estimates of dietary intake has been largely overlooked. In a multicenter, population-based case-control study of breast cancer in the United States, 1,588 newly diagnosed cases and 1,451 controls completed a self-administered food-frequency questionnaire. Initial evaluation suggested increased risk related to high intakes of calories, carbohydrates, fat, and protein. All nutrient associations were diminished after adjustment for calories. Evaluation by stage of disease revealed no relation of calories to risk among women with in situ disease, but elevated risks among women with localized (odds ratio [OR] = 1.33, 95 percent confidence interval [CI] = 1.0-1.7 highest cflowest quartile) or regional and distant disease (OR = 1.79, CI = 1.3-2.4). Further evaluation showed that the increased risk associated with calories was restricted to cases who reported having been treated with chemotherapy (OR = 1.66, CI = 1.3-2.1). A gradient of increasing risk with time interval from diagnosis to interview suggested the chemotherapy regimen itself and not necessarily characteristics of tumors requiring this treatment was responsible for the observed increased risk. These results indicate that epidemiologic studies of diet and breast cancer, particularly among young women, should evaluate possible bias related to post-diagnosis influences.

To compare selected characteristics of women with and without augmentation mammaplasty to identify differences between these 2 groups of women.White women identified as controls in previously conducted population-based, case-control studies formed the study population for the present cross-sectional analysis (N=3570).Interview information on selected characteristics was compared between women who had received augmentation mammaplasty (n=80) and other women (n=3490) using the prevalence odds ratio (pOR) as the measure of association.Women with breast implants were more likely to drink a greater average number of alcoholic drinks per week (foror =7 drinks vs 0 drinks: pOR=2.9, 95% confidence interval [CI]=1.5-5.5), be younger at first pregnancy (for age20 years vs age 20-29 years: pOR=1.6, 95% CI=1.0-2.7), be younger at first birth (for age20 years vs age 20-29 years: pOR=1.9, 95% C1=1.1-3.3), have a history of terminated pregnancies (foror =1 termination vs 0 terminations: pOR=2.0, 95% CI=1.2-3.4), have ever used oral contraceptives (pOR=2.2, 95% CI=1.0-4.7), have ever used hair dyes (pOR=4.5, 95% CI=1.3-15.4), and have had a greater lifetime number of sexual partners (foror =14 partners vsor =4 partners: pOR=8.9, 95% CI=3.1-25.5) than other women. A history of smoking, lactation, high blood pressure, or thyroid disorders, as well as the number of pregnancies, full-term births, or miscarriages, differed little between women with and without implants. Women with breast augmentation were much less likely to be heavy than other women (foror =74 kg vs56 kg: pOR=0.1, 95% CI=0.03-0.3).The differences we found between women with and without breast implants suggest that consideration and evaluation of confounding factors in future studies will help to clarify some of the long-term health consequences of having breast implants.

We analyzed the polymorphic (CAG)n and (GGN)n regions within the androgen receptor gene from participants in a population-based case-control study of prostate cancer in middle-aged (40-64 years) Caucasian men. The associations between repeat lengths and risk of prostate cancer and the effects of confounding and modifying factors, such as age, family history of prostate cancer, and body mass index, were evaluated. DNA was available for 301 cases and 277 controls. The overall age-adjusted relative odds of prostate cancer associated with the number of (CAG) repeats as a continuous variable was 0.97 [95% confidence interval (CI), 0.92-1.03], suggesting a 3% decrease in risk of prostate cancer for each additional (CAG) repeat. Further analyses identified several subgroups at increased risk. These were men with less than the median number of CAG repeats (22) that were younger [60 years; relative odds (RO), 1.47; 95% CI, 0.96-2.25], had an affected first-degree relative (RO, 1.59; 95% CI, 0.62-4.14), or were relatively thin (Quetelet index24.4; RO, 2.21; 95% CI, 1.07-4.69). Although only the latter result was statistically significant, these results are provocative and support the hypothesis that (CAG)n array length is a predictor of risk for prostate cancer. Similar analyses of (GGN)n showed that with the exception of men with a family history of prostate cancer and those in the highest quartile of body mass index, men withor = 16 repeats had higher risk estimates than did men with16 repeats. Overall, those men who hador = 16 repeats had a significant elevation in risk (RO, 1.60; 95% CI, 1.07-2.41). When both repeat lengths were considered jointly, the subgroup with two short repeats (CAG,22; GGN,or = 16) had a 2-fold elevation in odds (RO, 2.05; 95% CI, 1.09-3.84) relative to those with two long repeats (CAG,or = 22; GGN,16). These data suggest that determination of both androgen receptor repeats within germ-line DNA may be useful in assessing an individual's risk of developing prostate cancer.

To investigate whether, in the absence of galactosemia, relatively high intestinal lactase activity or low activity of an enzyme involved in galactose catabolism reduces fertility, as it does in the presence of galactosemia.Retrospective cohort study.Healthy women selected from the community.Fifty-three married women.Urinary galactose after an oral lactose challenge (a measure of intestinal lactase activity), erythrocyte galactose-1-phosphate uridyltransferase (transferase) activity, and transferase polymorphisms by isoelectric focusing.Pregnancy rate (number of pregnancies divided by number of months at risk) in the 12 months after stopping use of birth control to become pregnant.Relatively high urinary galactose was not related to a decreased rate of pregnancy during the first 12 months (or = 24.6 compared withor = 14.3 mg: relative risk [RR] = 1.9; 95% confidence interval [CI] = 0.86 to 4.0). Relatively high transferase activity was not related to an increased rate of pregnancy (or = 19.5 compared withor = 17.2 mumol/h per g hemoglobin: RR = 1.1; 95% CI = 0.56 to 2.4). Low-activity transferase polymorphisms were not related to a decreased rate (RR = 1.2; 95% CI = 0.58 to 2.5).Our study does not support the hypothesis that the biologic variation in galactose metabolism that exists in the general population influences infertility.

SUMMARY: IgA and IgG antibodies to cytoplasmic and secreted antigens of serotypes 4 and 8 of Mycobacterium avium and the percentage of agalactosyl immunoglobulin (%Gal[0]) were measured by ELISA in groups of blood donors, HIV seronegative persons, HIV seropositive persons with CD4+ cell counts>300/mm3 and AIDS patients co-infected with M. avium. No differences were found between the control groups, but HIV seropositive persons were distinguished by their increased %Gal[0] (p < 0.001) and increased IgA titre (p < 0.05) to secreted antigens of both serotypes of M. avium. Patients going on to develop aviumosis differed from other HIV-positive individuals, having more IgA to secreted antigens of serotype 8 (p < 0.03) and more IgG to secreted antigens of both serotypes (p < 0.001). After developing M. avium infection there was a further increase in %Gal[0] (p < 0.0001), IgA titres fell to both types of antigen from serotype 4 (p < 0.01) and sonicate antigen of serotype 8 (p < 0.001) and IgG fell to the secreted antigens of serotype 4 (p < 0.03). One interpretation of these observations is that antibody profiles to M. avium might be used to identify healthy persons at special risk of developing HIV seropositivity, and to identify persons with early AIDS who are likely to develop aviumosis.

To determine the risk of breast cancer in relation to the use of combined estrogen and progestin hormone replacement therapy (HRT).A population-based case-control study.The general female population of King County in western Washington State.Middle-aged (50 to 64 years) women, including 537 patients with incident primary breast cancer diagnosed between January 1, 1988, and June 30, 1990, who were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry and 492 randomly selected control women without a history of breast cancer.Breast cancer risk in relation to use of menopausal hormones.Menopausal hormones of some type had been used by 57.6% of breast cancer cases and 61.0% of comparison women. The women who had ever taken combined estrogen-progestin HRT, representing 21.5% of cases and 21.3% of controls, were not at increased risk of breast cancer (relative odds [RO] = 0.9; 95% confidence interval [CI], 0.7 to 1.3). Compared with nonusers of menopausal hormones, those who used estrogen-progestin HRT for 8 or more years had, if anything, a reduced risk of breast cancer (RO = 0.4; 95% CI, 0.2 to 1.0).On the whole, the use of estrogen with progestin HRT does not appear to be associated with an increased risk of breast cancer in middle-aged women. Nonetheless, since the use of combined estrogen-progestin HRT has only recently become prevalent, future investigations must assess whether breast cancer incidence is altered many years after estrogen-progestin HRT has been initiated, particularly among long-term users.

In this study of leprosy patients apparently cured by dapsone monotherapy, the polymerase chain reaction (PCR), one of the most reliable and sensitive DNA-based assays, was used for the specific detection of Mycobacterium leprae DNA. Sputum and slit-skin samples from 44 such patients at Baba Baghi Leprosy Sanatorium in Iran were examined. Primers for a 530-base-pair fragment of the gene encoding the 36-kDa antigen of M. leprae were used for the study. The PCR results were compared with microscopy for acid-fast bacilli. Of the 44 sputum samples, 2 were positive by PCR (4.5%) and of the 44 slit-skin swabs taken from the same patients, 10 were PCR positive (22.7%). Only one patient was PCR positive for both sputum and slit-skin specimens (2.3%). No positive results were found by acid-fast microscopy. In total, 11 of 44 (25%) patients in this study were found to be PCR positive for M. leprae, and it was thought probable that this indicated the presence of live organisms. Particularly interesting was the statistically significant association of positive results from slit-skin swabs with paucibacillary rather than multibacillary leprosy. It is suggested that whereas relapse or immunological reaction in paucibacillary disease may result from surviving organisms, in multibacillary leprosy this may be due to re-infection.

As the end of the twentieth century approaches new methods are needed for the treatment and control of tuberculosis. Vaccination needs to be rethought, and BCG either improved or replaced. Chemotherapy is no longer enough to meet the needs of impoverished countries, non-compliant patients, and increasingly drug-resistant organisms. The next major step forward should logically come from immunology. Following the clear differentiation of two pathways of cellular immune response to mycobacterial challenge, and the recent description of two functional types of helper T cells, ideas of what controls them have allowed the logical development of a potential new vaccine and a new immunotherapy. These are based on a killed environmental organism, Mycobacterium vaccae NCTC 11659. With this simple preparation together with chemotherapy we may be armed as never before to face the inevitable challenge that tuberculosis will present to the twenty first century. Parallels recognised between cell death in tuberculosis and infection with the human immunodeficiency virus open the possibility that the progress made in immunotherapy in tuberculosis might be applicable to HIV. If this proves the case then we may also have control over the latest, and worst, risk factor for tuberculosis at the time we need it most.

The effect of alcohol intake on mammographic densities and the possible interaction between these two factors in regard to the risk of breast cancer were assessed using information from the Breast Cancer Detection and Demonstration Project.Mammograms taken during the first year of screening for patients whose breast cancer was detected in the 5th year of follow-up (n = 266) and their matched controls (n = 301) were blindly assessed for the percent of mammographic densities, which were measured by planimetry.Among controls, alcohol intake was weakly, positively associated with the percent of mammographic densities (Spearman rank correlation coefficient, 0.09), although the association may have been the result of chance (P = 0.12). After adjustment for confounding factors, the lifetime alcohol intake did not appear to modify the effect of the percent mammographic densities on the risk of breast cancer (P for the interaction, 0.09).Longitudinal studies and larger case-control studies should be conducted to assess the relationship between diet and changes in mammographic densities further.