Calcium, vitamin D, and dairy foods and the occurrence of colon cancer in men

To examine the associations between intakes of calcium, Vitamin D, and dairy foods and the risk of colon cancer, the authors analyzed data from a prospective study of 47,935 US male professionals, 40-75 years of age and free of cancer in 1986. Within this cohort, 203 new cases of colon cancer were documented between 1986 and 1992. After adjusting for age and total energy intake, the authors found that the intake of calcium from foods and supplements was inversely associated with colon cancer risk (relative risk (RR) = 0.58, 95% confidence interval (CI) 0.39-087 between high and low intakes of calcium). However, after adjusting for confounding variables, they found that the trend was no longer statistically significant (p = 0.22), and the relative risk for the highest quintile group of intake was attenuated: 0.75 (95% CI 0.48-1.15). Similar results were observed for total vitamin D intake; the age- and energy-adjusted relative risk was 0.54% (95% CI 0/34-0/85) for the highest versus lowest quintile group, and this was attenuated in the multivariate model (RR = 0.66, 95% CI 0.42-1.05). The inverse association was weaker for dietary vitamin D (RR highest vs. lowest quintile = 0.88. 95% CI 0.54-1.42) and strongest for vitamin D arising from vitamin supplements (RR = 0.48, 95% CI 0.22-1.02). Thus, it is possible that other components of multivitamin use rather than vitamin D accounted for the reduction in risk. Consumption of milk and fermented dairy products was not significantly associated with the risk of colon cancer; individuals consuming two or more glasses of "whole" or skim milk per day had a relative risk of 1.09 (95% CI 0.69-1.72), compared with those who consumed "whole or skim milk less than once a month. These prospective data do not support the hypothesis that calcium intake is strongly protective against colon cancer risk, although a modest association cannot be excluded.     

Lowered risks of hypertension and cerebrovascular disease after vitamin/mineral supplementation: the Linxian Nutrition Intervention Trial

A total of 3,318 men and women from a region in rural China were randomized to receive daily either a multiple vitamin/mineral supplement or a placebo. Deaths that occurred in the participants were ascertained and classified according to cause over the 6-year period from 1985 to 1991. At the end of supplementation, blood pressure readings were taken, and the prevalence of hypertension was determined. There was a slight reduction in overall mortality in the supplement group (relative risk (RR) = 0.93, 95 percent confidence interval (CI) 0.75-1.16), with the decreased relative risk most pronounced for cerebrovascular disease deaths (RR = 0.63, 95 percent CI 0.37-1.07). This benefit was greater for men (RR = 0.42, 95 percent CI 0.19-0.93) than for women (RR = 0.93, 95 percent CI 0.44-1.98). Among the survivors, the presence of elevations in both systolic and diastolic blood pressures was less common in those who received the supplement (RR for men = 0.43, 95% CI 0.28-0.65; RR for women = 0.92, 95 percent CI 0.68-1.24). This study indicates that supplementation with a multivitamin/mineral combination may have reduced mortality from cerebrovascular disease and the prevalence of hypertension in this rural population with a micronutrient-poor diet.     

Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

The relation of intakes of specific fatty acids and the risk of coronary heart disease was examined in a cohort of 21,930 smoking men aged 50-69 years who were initially free of diagnosed cardiovascular disease. All men participated in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and completed a detailed and validated dietary questionnaire at baseline. After 6.1 years of follow-up from 1985-1988, the authors documented 1,399 major coronary events and 635 coronary deaths. After controlling for age, supplement group, several coronary risk factors, total energy, and fiber intake, the authors observed a significant positive association between the intake of trans-fatty acids and the risk of coronary death. For men in the top quintile of trans-fatty acid intake (median = 6.2 g/day), the multivariate relative risk of coronary death was 1.39 (95% confidence interval (CI) 1.09-1.78) (p for trend = 0.004) as compared with men in the lowest quintile of intake (median = 1.3 g/day). The intake of omega-3 fatty acids from fish was also directly related to the risk of coronary death in the multivariate model adjusting also for trans-saturated and cis-monounsaturated fatty acids (relative risk (RR) = 1.30, 95% CI 1.01-1.67) (p for trend = 0.06 for men in the highest quintile of intake compared with the lowest). There was no association between intakes of saturated or cis-monounsaturated fatty acids, linoleic or linolenic acid, or dietary cholesterol and the risk of coronary deaths. All the associations were similar but somewhat weaker for all major coronary events.     

The effect of varying molar ratios of potassium-magnesium citrate on thiazide-induced hypokalemia and magnesium loss

The host immune response to human papillomaviruses (HPVs) is believed to be an important determinant of progression of HPV-associated cervical neoplasia. Human leukocyte antigens (HLAs) are important in the presentation of foreign antigens to the immune system. Previous studies have suggested a possible association between HLA and cervical neoplasia, but the specific alleles found to be associated with disease have varied between studies. To further evaluate this issue, we conducted a nested case-control study within a 24,000-woman cohort study in the United States. A total of 711 women were selected for the study: 141 women diagnosed with high-grade squamous intraepithelial lesions (HSILs) of the cervix; 202 women diagnosed with low-grade SILs (LSILs); 166 women with no history of cervical neoplasia, but evidence of HPV-16 infection; and 202 women with no history of cervical abnormalities and who were HPV negative during follow-up as part of our cohort. Cervicovaginal lavage samples collected from participants were used for HPV testing by L1 consensus primer PCR and the Hybrid Capture tube test methods. DNA extracted from these same lavage samples were used for PCR-based HLA genotyping. Our results suggest a positive association between HLA B7 and HLA DQB1*0302 and disease. A negative association with disease was observed for HLA DRB1*1501-DQB1*0602 and DRB1*13. Associations were strongest when analyses were restricted to HPV-16-positive cases as follows. Compared with women who were cytologically normal and HPV negative, HLA B7 was associated with a 1.5-fold increased risk of HPV/LSIL [95% confidence interval (CI) = 0.95-2.5] and a 2.5-fold increased risk of HSIL (95% CI = 1.2-5.1). HLA DQB1*0302 was associated with a 1.5-fold increased risk of HPV/LSIL (95% CI = 0.94-2.4) and a 1.7-fold increased risk of HSIL (95% CI = 0.84-3.5). HLA DRB1*1501-DQB1*0602 was associated with a decreased risk of HSIL [relative risk (RR) = 0.21; 95% CI = 0.07-0.62]. HLA DRB1*13 was associated with a decreased risk of HPV/LSIL (RR = 0.78; 95% CI = 0.51-1.2) and HSIL (RR = 0.63; 95% CI = 0.30-1.3). Individuals who were either homozygous for DQB1*0302 or carriers of both B7 and DQB1*0302 were found to be at highest risk of disease (RR = 4.5, 95% CI = 1.5-14 for HPV/LSIL; and RR = 9.0, 95% CI = 2.4-34 for HSIL). No synergistic effect was observed for the alleles found to be associated with reduced risk of cervical neoplasia. Our findings support previous studies that have found HLA B7 and DQB1*0302 to be positively associated with cervical neoplasia and are consistent with those that have suggested that DRB1*13 is negatively associated with disease, but do not confirm previous assertions that DRB1*1501-DQB1*0602 increases the risk of cervical disease.     

erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer

BACKGROUND: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. METHODS: In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil (PF) or a combination of L-phenylalanine mustard, 5-fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided. RESULTS: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P=.02), lack of estrogen receptors (P=.008), and the number of positive lymph nodes (P=.0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors--DFS: relative risk of failure (RR)=0.60 (95% confidence interval [CI]=0.44-0.83), P=.001; survival: RR=0.66 (95% CI=0.47-0.92), P =.01; RFS: RR=0.58 (95% CI=0.42-0.82), P=.002; DDFS: RR=0.61 (95% CI=0.44-0.85), P=.003. However, it was not significant for patients with erbB-2-negative tumors-DFS: RR=0.96 (95% CI=0.75-1.23), P=.74; survival: RR =0.90 (95% CI=0.69-1.19), P=.47; RFS: RR=0.88 (95% CI=0.67-1.16), P=.37; DDFS: RR=1.03 (95% CI=0.79-1.35), P=.84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P=.02) and DDFS (P=.02) but not for survival (P= .15) or RFS (P=.06). CONCLUSIONS: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer.     

Risk of emergency care, hospitalization, and ICU stays for acute asthma among recipients of salmeterol

We used automated health insurance claims records of a New England insurer to assess the relation between salmeterol and severe nonfatal asthma. We identified 61,712 members who received a beta-agonist from January 1, 1993 to August 31, 1995, including 2, 708 recipients of salmeterol. Compared with recipients of other beta-agonists, future salmeterol recipients had higher rates of asthma hospitalization and dispensings of asthma medications during the year before they received salmeterol. We selected as a comparison group 3,825 recipients of sustained-release theophylline. We defined a baseline period as the year before the start of the follow-up period, and we characterized patients according to age, sex, calendar period, presence of baseline hospitalizations for asthma, presence of chronic obstructive pulmonary disease (COPD), and baseline dispensings of asthma medications. After adjusting for baseline factors, incidence rates of severe asthma in the salmeterol group were not elevated for emergency care (rate ratio estimate [RR] = 0.69, 95% confidence intervals [CI] = 0.42, 1.11), hospitalization (RR = 1.09, 95% CI = 0.60, 1.98), or intensive care unit (ICU) stays (RR = 0.81, 95% CI = 0.25, 2.62). We conclude that salmeterol was prescribed preferentially to high-risk patients and, after adjusting for baseline risk, salmeterol recipients did not have a greater risk than theophylline recipients of severe nonfatal asthma.     

Augmentation of natural killer cell activity in mice by oral administration of transforming growth factor-beta

OBJECTIVE: To analyze the effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis (AS). METHODS: Three hundred sixty-three white British AS patients were studied; 149 were carefully assessed for a range of clinical manifestations, and disease severity was assessed using a structured questionnaire. Limited HLA class I typing and complete HLA-DR typing were performed using DNA-based methods. HLA data from 13,634 healthy white British bone marrow donors were used for comparison. RESULTS: A significant association between DR1 and AS was found, independent of HLA-B27 (overall odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1-1.8, P = 0.02; relative risk [RR] 2.7, 95% CI 1.5-4.8, P = 6 x 10(-4) among homozygotes; RR 2.1, 95% CI 1.5-2.8, P = 5 x 10(-6) among heterozygotes). A large but weakly significant association between DR8 and AS was noted, particularly among DR8 homozygotes (RR 6.8, 95% CI 1.6-29.2, P = 0.01 among homozygotes; RR 1.6, 95% CI 1.0-2.7, P = 0.07 among heterozygotes). A negative association with DR12 (OR 0.22, 95% CI 0.09-0.5, P = 0.001) was noted. HLA-DR7 was associated with younger age at onset of disease (mean age at onset 18 years for DR7-positive patients and 23 years for DR7-negative patients; Z score 3.21, P = 0.001). No other HLA class I or class II associations with disease severity or with different clinical manifestations of AS were found. CONCLUSION: The results of this study suggest that HLA-DR genes may have a weak effect on susceptibility to AS independent of HLA-B27, but do not support suggestions that they affect disease severity or different clinical manifestations.     

Risk indicators for inflammatory bowel disease

We investigated the association between different risk indicators and inflammatory bowel disease in a case-control study based on the population of Stockholm County during 1980-1984. Information on physical activity, oral contraceptives, some previous diseases and childhood characteristics was collected using a postal questionnaire for 152 cases of Crohn's disease, 145 cases of ulcerative colitis, and 305 controls. The relative risk (RR) of Crohn's disease was inversely related to regular physical activity and estimated at 0.6 (95% CI: 0.4-0.9) and 0.5 (95% CI: 0.3-0.9) for weekly and daily exercise, respectively. Having psoriasis prior to the inflammatory bowel disease was associated with an increased relative risk of Crohn's disease (RR = 2.9, 95% CI: 1.1-7.9). Use of oral contraceptives was associated with an increased RR of 1.7 for both Crohn's disease and ulcerative colitis. Crohn's disease confined to the colon and total ulcerative colitis at diagnosis were most strongly associated with oral contraceptives.     

Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance

BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.     

Gastric carcinosarcoma (sarcomatoid carcinoma) with rhabdomyoblastic and osteoblastic differentiation

Using data from the Health Professionals Follow-Up Study, we prospectively examined the relationships between height, body mass index, waist and hip circumferences, and risk of total and advanced (extraprostatic and metastatic) prostate cancer. In addition, we assessed adiposity during childhood, adolescence, and early, middle, and late adulthood using pictograms in relation to prostate cancer risk. Between 1986 and 1994, 1,369 cases of prostate cancer (excluding stage A1) were confirmed in 47,781 men. Adult body mass index and waist and hip circumferences were not appreciably related to risk of total prostate cancer or advanced prostate cancer. In contrast, preadult (age 10) obesity assessed in 33,336 men in 1988 was prospectively related to lower risk of advanced [relative risk (RR) = 0.72 with 95% confidence interval (CI) = 0.47-1.10, between high and low quintiles; P(trend) = 0.06] and metastatic prostate cancer (RR = 0.38 with 95% CI = 0.19-0.77; P(trend) = 0.004). For the advanced lesions, an association was observed with height (RR = 1.68 with 95% CI = 1.16-2.43 for men 74 inches or taller, relative to men 68 inches or shorter; P(trend) = 0.01). In an analysis limited to particularly aggressive forms of prostate cancer, i.e., cases found to be metastatic at time of diagnosis between 1988 and 1994 after a negative digital rectal examination in 1988, we found that obesity at ages 5 and 10 had a strong inverse association (RR = 0.16 with 95% CI = 0.05-0.54, between high and low quintiles at age 10) and that tallness had a strong direct association with risk of metastatic disease (RR = 2.29 with 95% CI = 1.04-5.05, for height > or = 74 inches versus < or = 68 inches). Our findings suggest that the preadult hormonal milieu, as reflected in attained height and childhood obesity, may have a strong influence on prostate carcinogenesis.     

Impact of major cardiovascular disease risk factors, particularly in combination, on 22-year mortality in women and men

BACKGROUND: The appropriateness of current cardiovascular disease (CVD) risk factor guidelines in women continues to be debated. OBJECTIVE: To present new data on the appropriateness of current CVD risk factor guidelines, for women and men, from long-term follow-up of a large population sample. METHODS: Cardiovascular disease risk factor status according to current clinical guidelines and long-term impact on mortality were determined in 8686 women and 10503 men aged 40 to 64 years at baseline from the Chicago Heart Association Detection Project in Industry; average follow-up was 22 years. RESULTS: At baseline, only 6.6% of women and 4.8% of men had desirable levels for all 3 major risk factors (cholesterol level, <5.20 mmol/L [<200 mg/dL]; systolic and diastolic blood pressure, <120 and <80 mm Hg, respectively; and nonsmoking). With control for age, race, and other risk factors, each major risk factor considered separately was associated with increased risk of death for women and men. In analyses of combinations of major risk factors, risk increased with number of risk factors. Relative risks (RRs) associated with any 2 or all 3 risk factors were similar: for coronary heart disease mortality in women, RR= 5.72 (95% confidence interval [CI], 2.35-13.93), and in men, RR = 5.51 (95% CI, 3.10-9.77); for CVD mortality in women, RR = 4.54 (95% CI, 2.33-8.84), and in men, RR = 4.12 (95% CI, 2.56-6.37); and for all-cause mortality in women, RR = 2.34 (95% CI, 1.73-3.15), and in men, RR = 3.20 (95% CI, 2.47-4.14). Absolute excess risks were high in women and men with any 2 or all 3 major risk factors. CONCLUSIONS: Combinations of major CVD risk factors place women and men at high relative, absolute, and absolute excess risk of coronary heart disease, CVD, and all-cause mortality. These findings support the value of (1) measurement of major CVD risk factors, especially in combination, for assessing long-term mortality risk and (2) current advice to match treatment intensity to the level of CVD risk in both women and men.     

Genetic susceptibility and head injury as risk factors for Alzheimer's disease among community-dwelling elderly persons and their first-degree relatives

We performed a community-based study to investigate the relationship of genetic susceptibility and head injury to Alzheimer's disease (AD) in 138 patients with AD and 193 healthy elderly control subjects. Data concerning presence or absence of dementia and certain exposures were also obtained from 799 first-degree relatives of the patients and 1,238 first-degree relatives of the control subjects. Adjusting for age, gender, and other risk factors, the odds ratio for AD associated with head injury was 3.7 (95% confidence interval [CI], 1.4-9.7). The association was highest for head injuries that occurred after age 70. The risk of AD was higher in first-degree relatives of patients with onset prior to age 70 than in relatives of control subjects (risk ratio [RR] = 2.5; 95% CI, 1.1-5.6). The risk was not increased for relatives of patients with onset of AD at age 70 or older. Compared with relatives without head injury, the risk of AD was increased among both head-injured relatives of patients (RR = 5.9; 95% CI, 2.3-14.8) and head-injured relatives of control subjects (RR = 6.9; 95% CI, 2.5-18.9). Our results are consistent with the hypothesis that severe head injury and genetic susceptibility are associated with AD. Both associations concur with current concepts regarding the role of amyloid in AD. Although we regard head injury, like genetic susceptibility, to be a putative risk factor for AD, the temporal relationship between head injury and AD warrants further investigation.     

Physical activity and risk of colorectal cancer in men and women

We examined the association between self-reported occupational and recreational physical activity and the subsequent risk of colorectal cancer in a population-based cohort in Norway. During a mean follow-up time of 16.3 years for males and 15.5 years for females, 236 and 99 colon cancers and 170 and 58 rectal cancers were observed in males and females, respectively, among 53,242 males and 28,274 females who attended the screening between 1972 and 1978. Physical activity at a level equivalent to walking or bicycling for at least four hours a week during leisure-time was associated with decreased risk of colon cancer among females when compared with the sedentary group (RR = 0.62, 95% CI 0.40-0.97). Reduced risk of colon cancer was particularly marked in the proximal colon (RR = 0.51, 95% CI 0.28-0.93). This effect was not observed for occupational physical activity alone, probably due to a narrow range of self-reported physical activity at work among females. However, by combining occupational and recreational physical activity we observed an inverse dose-response effect as increasing total activity significantly reduced colon cancer risk (P for trend = 0.04). Among males 45 years or older at entry to the study, an inverse dose-response effect was observed between total physical activity and colon cancer risk (P for trend = 0.04). We also found in males a stronger preventive effect for physical activity in the proximal as compared to distal colon. In addition, we found a borderline significant decrease in colon cancer risk for occupational physical activity in males 45 years or older when compared to the sedentary group (RR = 0.74, 95% CI 0.53-1.04). All results were adjusted for age, body mass index, serum cholesterol and geographic region. No association between physical activity and rectal cancer was observed in males or females. The protective effect of physical activity on colon cancer risk is discussed in regard to energy balance, dietary factors, age, social class, body mass index and gastrointestinal transit time.     

Does psychological distress predict disability?

STUDY OBJECTIVE: To evaluate psychological distress as a predictor of disability due to common chronic disorders. STUDY POPULATION AND METHODS: A 10-year follow-up study was carried out among a representative cohort (N = 8655) of 18-64 year old Finnish farmers, who had participated in a health survey in 1979 and were able to work at baseline. A record linkage with the nationwide register of the Social Insurance Institution was made to identify disability pensions granted between 1980 and 1990 in the cohort. The medical certificates of 1004 (11.6%) prematurely retired farmers were reviewed to confirm and classify disabling conditions. A sum score based on self-reports of 11 symptoms at the baseline was used as a measure of psychological distress. RESULTS: After adjustment for age, sex, smoking and body mass index, the cause-specific relative risks (RR) (95% confidence intervals [CI]) of disability in the highest quartile of the psychological distress score as compared with the lowest quartile were for myocardial infarction 2.34 (95% CI: 1.17-4.69), for depression 2.50 (95% CI: 1.09-5.72), for neck-shoulder disorders 1.98 (95% CI: 1.26-3.11), for unspecified low-back disorders 1.76 (95% CI: 1.24-2.49), for knee osteoarthritis 1.55 (95% CI: 0.91-2.63) and for trip osteoarthritis 0.89 (95% CI: 0.42-1.85). The corresponding RR for overall disability was 1.76 (95% CI: 1.44-2.14) in the highest quartile of psychological distress score as compared with the lowest quartile. CONCLUSIONS: Psychological distress is an independent risk factor for disability. Its predictive significance varies between disorders leading to functional deterioration. The association mechanisms are likely to vary from one disorder to another.     

The association of calcium and vitamin D, and colon and rectal cancer in Wisconsin women

BACKGROUND: Calcium and vitamin D have been hypothesized to reduce colorectal cancer risk. Epidemiological evidence, however, is mixed. METHODS: To explore those relationships, data were collected as part of a population-based, case-control study of colorectal cancer in Wisconsin women (678 controls, 348 colon and 164 rectal cancer cases). A semi-quantitative food frequency questionnaire was used to ascertain food and dietary supplement intake 2 years prior to interview. Logistic regression models were used to calculate odds ratios (OR). RESULTS: Higher levels of calcium intake were associated with reduced colon and rectal cancer risk. The following adjusted OR and 95% confidence intervals (CI) were observed, comparing the fifth quintile (based on control intake) with the first: colon cancer: OR = 0.6, 95% CI: 0.4-1.0, P-trend: 0.03; rectal cancer: OR = 0.6, 95% CI: 0.3-1.1, P-trend: 0.07. Similar relationships were observed for vitamin D intake, although OR were closer to the null value and did not always behave in a step-wise fashion (fifth quintile versus the first--colon cancer: OR = 0.7, 95% CI: 0.4-1.1, P-trend: 0.05; rectal cancer: OR = 0.8, 95% CI: 0.5-1.5, P-trend: 0.42). CONCLUSION: These data support a protective association of calcium on colon and rectal cancer risk.     

Protein kinases A and C phosphorylate purified Ca2+-ATPase from rat cortex, cerebellum and hippocampus

Previous knowledge on risk factors for oral, pharyngeal, laryngeal, and esophageal cancer has been based mainly on case-control studies. In the present study, the impact of alcohol consumption, tobacco smoking, and dietary factors on upper aerogastric tract cancer risk was studied in a cohort of 10,960 Norwegian men followed from 1968 through 1992, in which period a total of 71 upper aerogastric tract cancers occurred. The relative risk (RR) of cancer was 3.9 (95 percent confidence interval [CI] = 2.1-7.1) for the highest consumption group of alcohol and 4.7 (CI = 1.7-13.2) for the highest smoking level, compared with the respective reference groups. Among the dietary items, high consumption of oranges was associated with reduced cancer risk (RR = 0.5, CI = 0.3-1.0), as was high consumption of bread (RR = 0.2, CI = 0.1-0.5). Frequent consumption of beef and bacon increased relative cancer risk bordering on significance. The present results are largely in accordance with previous studies. The decreased risk associated with a high intake of bread deserves further investigation.     

Presence of soluble amyloid beta-peptide precedes amyloid plaque formation in Down''s syndrome

We studied the association between the operative course of transurethral resection of the prostate (TURP) and the morbidity of acute myocardial infarction (AMI) in a cohort comprising 846 patients who underwent this operation between 1983 and 1992. Up to the end of 1993, a total of 69 patients had developed AMI, of which 10 patients had a reinfarction. The relative risk associated with absorption of 500 ml or more of the irrigating medium during surgery was 1.6 [95% confidence interval (CI) = 0.9-3.0] for a first-time AMI after TURP, 6.1 (95% CI = 1.8-20.7) for a reinfarction, and 2.2 (95% CI = 1.3-3.9) for a first-time or a reinfarction combined. A blood loss of 275 ml or more was associated with a decreased relative risk (RR = 0.4; 95% CI = 0.2-0.8) of a first-time AMI after TURP. Patients who lost less than 275 ml of blood and absorbed 500 ml or more of irrigating fluid during surgery had 4.4 times the risk of having an acute myocardial infarction (RR = 4.4; 95% CI = 1.7-11.8). These results appear to indicate that the operative course of TURP is important to the development of AMI over an extended period of time.     

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-->T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-->carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.     

Histochemical and laser scanning microscopy characterization of the hydroxyapatite-bone interface: an experimental study in rabbits

OBJECTIVES: To assess the relationship between haematocrit and risk of stroke. DESIGN: Prospective study of a cohort of men followed up for 9.5 years. SETTING: General practices in 24 towns in England, Scotland and Wales (British Regional Heart Study). SUBJECTS: A total of 7735 men aged 40-59 years at screening, selected at random from one general practice in each of 24 towns. MAIN OUTCOME MEASURES: Fatal and non-fatal strokes. RESULTS: During a follow-up period of 9.5 years for all men there were 123 stroke events (33 fatal) in the 7346 men in whom the haematocrit level had been determined. In the cohort as a whole, risk of stroke was significantly raised at haematocrit levels > or = 51% (relative risk [RR] = 2.5; 95% confidence intervals [CI] 1.2-5.0) after adjustment for age, social class, smoking, body mass index, physical activity, presence of diabetes and pre-existing ischaemic heart disease. Further adjustment for systolic blood pressure did not attenuate this association (RR = 2.4; 95% CI 1.2-4.9). A raised haematocrit was associated with an increase of stroke only in men with hypertension (systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 90 mmHg or on regular antihypertensive treatment). No increased risk of stroke was seen at the higher haematocrit level (> or = 51%) in normotensive men. At haematocrit levels below 51%, hypertension was associated with a three-fold increase in risk of stroke compared with normotension (RR = 3.4, 95% CI 2.3, 5.1). At haematocrit levels > or = 51%, hypertension was associated with a nine-fold increase in risk of stroke compared with normotension (RR = 9.3; 95% CI 4.2, 21.0). Exclusion of men receiving regular antihypertensive therapy did not alter the strong associations seen. CONCLUSION: The data suggest that an elevated haematocrit is an independent risk factor for stroke and that it interacts synergistically with elevated blood pressure.     

Towards the predictability of drug-lipid membrane interactions: the pH-dependent affinity of propanolol to phosphatidylinositol containing liposomes

AIMS: The purpose of the study was to assess whether fluoxetine would enhance retention in a naltrexone (NTX) treatment programme. DESIGN: Randomized clinical trial. SETTING: The clinical trial was conducted in two Drug Dependence Centres (DCs) of the Basque Country, Spain over a 1-year period. These DCs routinely used naltrexone as part of their treatment. PARTICIPANTS: A total of 112 heroin addicts included in a naltrexone treatment programme were randomly allocated to two groups of 56 patients each. INTERVENTION: One group received 20 mg/24 h of fluoxetine for the first 6 months, while the remaining 56 patients were used as controls. No placebo was used. MEASUREMENTS: Retention rates and hazard functions were estimated. The risk difference and relative risk were also calculated at 6 and 12 months. FINDINGS: The survival functions showed significantly higher retention rates in the fluoxetine group than among the controls. The risk difference at both 6 months (RD6 = 0.23, CI 95% = 0.06-0.42) and 12 months (RD12 = 0.21, CI 95% = 0.09-0.39) favoured the fluoxetine group, with a greater dropout risk at both times among the controls (RR6 = 1.81, CI 95% = 1.11-2.94; RR12 = 1.46, CI 95% = 1.04-2.04). CONCLUSIONS: The study showed that the combination of fluoxetine and naltrexone produced significantly greater retention than in patients given only naltrexone. Placebo-controlled trials are warranted to assess how far this reflects a specific pharmacological effect.