Association of malignant brain tumors and cancers of other sites

PURPOSE: We conducted an exploratory study of brain tumors that occurred as a second primary malignancy to identify potential risk factors for brain tumors. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated the sex-specific standardized incidence ratio (SIR), adjusted to age and time period, as an estimate of the relative risk (RR) of developing a second primary brain tumor following other cancers. RESULTS: We found an elevated RR of brain tumors after bladder cancer in both men (RR, 1.7; 95% confidence interval [CI], 1.2 to 2.3) and women (RR, 1.7; 95% CI, 0.8 to 3.2); this effect was present for both astrocytoma and glioblastoma multiforme. Elevated RRs of brain tumors were also found after sarcoma (RR, 4.4; 95% CI, 1.8 to 9.0) and leukemia (RR, 2.9; 95% CI, 1.6 to 4.8) in men, and after colorectal cancer (RR, 1.8; 95% CI, 1.3 to 2.4) and endometrial cancer (RR, 1.4; 95% CI, 1.0 to 1.9) in women. The highest RR observed in this study was for CNS lymphoma following any first primary malignancy in men (RR, 7.9; 95% CI, 5.5 to 11.0). CONCLUSION: The associations of brain tumors with bladder, colorectal, and endometrial cancers in women, and an increased occurrence of CNS lymphoma as a second malignancy in men, are new findings that have not been described previously.     

Epilepsy--a time for change?

OBJECTIVE: To examine the association between postmenopausal hormone use and cholecystectomy. METHODS: A prospective cohort study was performed, with follow-up every 2 years. Participants were 54,845 postmenopausal United States nurses, who reported both hormone use and cholecystectomy on mailed questionnaires. RESULTS: Cholecystectomy was reported by 1750 women during 8 years of follow-up. After adjusting for confounding factors, women currently using postmenopausal hormones were at an increased risk of cholecystectomy (relative risk [RR] 2.1, 95% confidence interval [CI] 1.9-2.4) compared to never-users. For current users, the risk of cholecystectomy increased with increasing duration of hormone use (RR 2.6, 95% CI 2.2-3.1 for 10 years or more) and higher doses of estrogen (RR 2.4, 95% CI 2.0-2.9 for users of 1.25 mg or more). Although the risk for past hormone users decreased substantially in women who had discontinued use 1-2.9 years ago (RR 1.6, 95% CI 1.2-2.0), a small risk persisted for women who had stopped taking hormones 5 or more years previously (RR 1.3, 95% CI 1.1-1.6). However, after controlling for time since last use, duration of past use had little or no effect on the risk of cholecystectomy (RR 1.4 and RR 1.7 for past users of less than 2 years and 10 or more years' duration, respectively). CONCLUSION: Women using postmenopausal hormones are at an increased risk of cholecystectomy. Women and their physicians should consider the spectrum of risks and benefits when deciding whether to take hormones.     

Herpes zoster, immunological deterioration and disease progression in HIV-1 infection

OBJECTIVE: To study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. DESIGN AND METHODS: A total of 966 homosexual participants in The Amsterdam Cohort Study were studied. Herpes zoster was defined by its characteristic clinical presentation. Incidence was calculated using Poisson regression, cumulative incidence by the Kaplan-Meier product-limit method and the prognostic value was evaluated using Cox proportional hazards model. RESULTS: The incidence of first episodes of herpes zoster was 3.31 per 1000 person-years (PY) in HIV-seronegatives and 51.51 per 1000 PY in HIV-1-seropositive individuals. Recurrences only occurred in HIV-1-positive patients (25.6%). Cumulative incidences of first episodes increased linearly with the duration of follow-up. In HIV-1-seropositives the incidence was 31.2 per 1000 PY at CD4+ cells > or = 500 x 10(6)/l, 47.2 per 1000 PY [relative risk (RR), 1.51; 95% confidence interval (CI), 0.78-2.94] at CD4+ cells 200-499 x 10(6)/l and 97.5 per 1000 PY (RR, 3.13; 95% CI, 1.54-6.32) at CD4+ cells < 200 x 10(6)/l. Besides CD4+ cell counts, CD3 monoclonal antibodies and phytohaemagglutinin-induced T-cell reactivity were independent predictors for herpes zoster. The hazard ratio for AIDS after herpes zoster was 1.6 (95% CI, 1.1-2.4) and for death 1.7 (95% CI, 1.1-2.5), but these were not independent from CD4+ cell counts. CONCLUSION: In HIV-1 infection the incidence of herpes zoster increases with the decrease of CD4+ cell counts and T-cell reactivity, but herpes zoster is not an independent predictor for disease progression.     

Cuticle chirality and body handedness in Caenorhabditis elegans

BACKGROUND AND PURPOSE: Norway has the highest reported incidence of hip fractures in western Europe. Little is known about the epidemiology of falls in Norway where the winter season is long and dark. The objective of this work was to study reported falls and their consequences among elderly Norwegians living at home. METHODS: A cross-sectional design was used for the study. Interviews were performed in the homes of 431 subjects, aged 67-97 years, living at home. Information on falling was gathered through six questions: whether the subject had fallen during the last six months, and if so, how many falls they had, where the last fall occurred, its perceived reason, the activity the subject had been engaged in when the fall occurred, and the resulting injury. RESULTS: In all, 24.1% of subjects reported falling during the last six months, and 9.5% had suffered more than one fall. Falls were most frequently linked to external events (63.1%). Outdoor falls were more frequent (59.0%; 95% CI = 51.2-82.0) than indoor falls. Older subjects were associated with more frequent indoor falls (p < 0.05), but gender was not significant. Fifty-one per cent of subjects had fallen while walking and 53% had suffered an injury from the last fall. In 13.4% of the women and 16.2% of the men, the last fall had resulted in a fracture. CONCLUSIONS: Compared to the results of other studies from industrialized Western countries, a similar crude fall rate, similar frequency and similar type of injury were found. However, in contrast to other studies, no gender difference was observed with regard to falling, place of falling and fracture rate.     

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.     

Intake of beer, wine, and spirits and risk of stroke : the copenhagen city heart study

BACKGROUND and PURPOSE: Alcohol consumption has been associated with a protective effect on risk of ischemic stroke. There may, however, be differences in the effect of beer, wine, and spirits due to properties other than ethanol, a topic that has gained only little attention in stroke research. METHODS: Our analysis was a prospective cohort study of 13 329 eligible men and women, aged 45 to 84 years, participating in the Copenhagen City Heart Study. Information on alcohol habits and a number of socioeconomic and health-related factors was obtained at baseline. During 16 years of follow-up, 833 first-ever strokes occurred. Data were analyzed by means of multiple Poisson regression. RESULTS: We found indications of a U-shaped relation between intake of alcohol and risk of stroke. In analyses adjusted for age, sex, and smoking, intake of wine on a monthly, weekly, or daily basis was associated with a lower risk of stroke compared with no wine intake (monthly: relative risk [RR], 0. 83; 95% CI, 0.69 to 0.98; weekly: RR, 0.59; 95% CI, 0.45 to 0.77; daily: RR, 0.70; 95% CI, 0.46 to 1.00). This effect of wine intake remained after complete adjustment for confounding variables (monthly: RR, 0.84; 95% CI, 0.70 to 1.02; weekly: RR, 0.66; 95% CI, 0.50 to 0.88; daily: RR, 0.68; 95% CI, 0.45 to 1.02). There was no association between intake of beer or spirits on risk of stroke. CONCLUSIONS: The differences in the effects of beer, wine, and spirits on the risk of stroke suggest that compounds in the wine in addition to ethanol are responsible for the protective effect on risk of stroke.     

Can sonographic signs predict conversion of laparoscopic to open cholecystectomy?

BACKGROUND: The aim of this study was to determine whether sonographic signs can predict the risk for conversion of laparoscopic (LC) to open cholecystectomy (OC). METHODS: All 346 patients who underwent LC at our institution between January 1, 1993, and March 1, 1996, were studied retrospectively. Patients who had no sonographic examination during 6 months prior to surgery and patients treated by inexperienced surgeons were excluded from the study. Patient characteristics and sonographic parameters were evaluated by univariate and multivariate analysis, using conversion to OC as a dependent variable. RESULTS: In 23 of 134 patients (17.2%), LC was converted to OC. In the univariate analysis, gallbladder distention (>4.5 cm; relative risk [RR] 3.5; 95% confidence intervals [CI] 1.7-5.3), stone impaction (RR 2.4; 95% CI 1.1-5.1), thickened gallbladder wall (RR 2.4; 95% CI 1.2-5.1), and acute cholecystitis (RR 2.6; 95% CI 1.1-6.7) were able to predict the need for conversion. Logistic regression defined only the sonographic sign of distention of the gallbladder as a predictor of conversion. CONCLUSIONS: Gallbladder distention as a sonographic sign is associated with a high relative risk for conversion. The predictive value of sonographic signs for conversion requires further assessment in a prospective study.     

Risk factors for subarachnoid hemorrhage: a systematic review

BACKGROUND AND PURPOSE: Knowledge of modifiable risk factors for subarachnoid hemorrhage (SAH) is important in terms of prevention. We therefore conducted a systematic review of studies on risk factors for SAH, with emphasis on sufficiently precise criteria for the diagnosis of SAH. METHODS: To identify studies we performed a Medline search from 1966 to 1994 and searched the reference lists of all relevant publications. Studies were included only if they fulfilled predefined methodological criteria. Case-control studies were included if the diagnosis of SAH was proved by CT, angiography, or autopsy in at least 70% of patients. Longitudinal studies were included if the criteria for SAH were based on a review of the medical records. RESULTS: Nine longitudinal studies and 11 case-control studies were included. Significant risk factors were as follows: (1) smoking (relative risk [RR] for longitudinal studies, 1.9; 95% confidence interval [CI], 1.5 to 2.3; odds ratio [OR] for case-control studies, 3.5; 95% CI, 2.9 to 4.3); (2) hypertension (RR, 2.8; 95% CI, 2.1 to 3.6; OR, 2.9; 95% CI, 2.4 to 3.7) and (3) drinking 150 g or more of alcohol per week (RR, 4.7; 95% CI, 2.1 to 10.5; OR, 1.5; 95% CI, 1.1 to 1.9). Use of oral contraceptives, hormone replacement therapy, hypercholesterolemia, and physical activity were not significantly related to the risk of SAH. CONCLUSIONS: We conclude that smoking, hypertension, and alcohol abuse are important risk factors for SAH. Reduction of exposure to these risk factors might result in a decreased incidence of SAH.     

Health status of persons with acute radiation sickness caused by Chernobyl AES accident

Chemical prophylaxis is known to reduce the venographic prevalence of deep-vein thrombosis (DVT) after total knee replacement (TKR), but it is uncertain whether this affects the incidence of symptoms. Further analysis depends on the basic epidemiology of thromboembolic symptoms. We therefore studied the pattern of such symptoms in a consecutive series of 1000 patients with primary TKR, with particular reference to risk factors and prophylaxis. We reviewed all the clinical records and contacted all the patients individually, noting risk factors, prophylaxis, symptomatic pulmonary embolus (PE) or DVT and its timing, death and its causes, and all complications. All the patients wore antiembolism stockings, 83% had regional anaesthesia and 33.9% had chemical prophylaxis. One patient died from PE on the day of surgery, having had no prophylaxis giving a rate of 0.1% (95% CI 0.003% to 0.56%). Symptomatic, radiologically confirmed thromboembolism (VTE) was common with a rate of 10.6% (95% CI 8.7% to 12.5%). There was a similar incidence of VTE in those with and without chemical prophylaxis (10.1% v 10.5%, RR 0.96, NS). VTE was more common in patients with risk factors (15.1% v 9.5%, RR 1.59, p = 0.02) and tended to occur earlier in this group (median day of onset 5 v 7, p = 0.01). Chemical prophylaxis did not reduce the frequency of symptomatic thromboembolism in either those with risk factors (RR 0.81, p = 0.5) or those without them (RR 0.94, p = 0.8). Haematoma or wound dehiscence was more common in those having chemical prophylaxis (11.9% v 6.9%; RR 1.73 95% CI 1.16 to 2.60). Readmission for symptomatic, radio-logically confirmed thromboembolism involved 1.1% of patients (95% CI 0.55% to 2.1%). Four patients were readmitted with proven non-fatal PE and six with proven DVT (the latest on day 40). Our results show that the main risk factor for thromboembolism was TKR itself; chemical prophylaxis did not reduce the incidence of symptomatic thromboembolism but gave an increased perception of side-effects. New prophylactic methods or combinations of methods are needed, with their efficacy compared by randomised controlled studies of both the clinical and the radiological effect.     

Transesophageal echocardiography to assess embolic risk in patients with atrial fibrillation. ELAT Study Group. Embolism in Left Atrial Thrombi

BACKGROUND: Transesophageal echocardiography visualizes the left atrium and its appendage, thrombi, and spontaneous echocardiographic contrast. OBJECTIVE: To assess the association of transesophageal echocardiographic characteristics with stroke or embolism in atrial fibrillation. DESIGN: Multicenter observational follow-up study. SETTING: Hospitals in Austria and Slovakia. PATIENTS: 409 outpatients with nonrheumatic atrial fibrillation and without recent stroke. INTERVENTION: Patients with thrombi received anticoagulation, and patients without thrombi received aspirin. MEASUREMENTS: Primary events were stroke or embolism. Secondary events were death not caused by stroke or embolism and need for anticoagulation. RESULTS: In the left atrium or left atrial appendage, 10 patients (2.5%) had thrombi and 47 (12%) had spontaneous echocardiographic contrast. The appendage had a mean (+/- SD) length of 44+/-10 mm, a mean width of 23+/-6 mm, and a mean area of 5.8+/-2.5 cm2. Follow-up ranged from 1 to 74 months (mean, 58 months). Fifty patients had stroke or embolism, 53 died of a cause other than stroke or embolism, and 38 required anticoagulation. On univariate analysis, thrombi (risk ratio, 3.9 [95% CI, 1.4 to 10.1]; P = 0.009), length of the left atrial appendage (risk ratio, 1.6 [CI, 1.05 to 2.5]; P = 0.03), and width of the left atrial appendage (risk ratio, 2.4 [CI, 1.2 to 4.81; P = 0.01) were associated with stroke or embolism. Multivariate analysis identified hypertension (risk ratio, 3.6 [CI, 1.8 to 8.4]; P = 0.001), previous stroke (risk ratio, 3.7 [CI, 1.5 to 7.5]; P = 0.002), and age (risk ratio, 1.1 [CI, 1.0 to 1.11; P < 0.001) as risk factors for stroke or embolism and provided evidence of an association between thrombi and stroke or embolism (risk ratio, 2.4 [CI, 0.9 to 6.9]; P = 0.09). CONCLUSIONS: In outpatients with atrial fibrillation and without recent stroke, thrombi of the left atrium or left atrial appendage and length and width of the left atrial appendage were associated with stroke or embolism in univariate analysis. In a multivariate analysis, age, hypertension, and previous stroke were risk factors for stroke or embolism, and thrombi of the left atrium or left atrial appendage were possible risk factors. In these patients, history may be more useful than transesophageal echocardiography for the assessment of embolic risk.     

Colorectal cancer incidence and survival among Alaska Natives, 1969-1993

BACKGROUND: Although colorectal cancer rates are low among most groups of Native Americans in North America, rates for Alaska Natives have been substantially elevated compared with US rates for all races combined. METHODS: To better describe the epidemiology of colorectal cancer incidence and survival among Alaska Natives, stratified by gender and tribal/ethnic affiliation, we examined data collected by the Alaska Native Cancer Registry 1969-1993. We calculated age-adjusted and age-specific incidence as well as actuarial survival rates, and examined histological type, site, stage at diagnosis, and treatment. We compared these data to colorectal cancer data from whites living in western Washington. RESULTS: In all, 587 colorectal cancer cases were identified among Alaska Natives over the 25-year period, for an age-adjusted annual incidence rate of 71.4/100000 in women, and 69.3/100000 in men. Compared to Alaska Indians, colon cancer rates were significantly higher in Aleuts (relative risk [RR] = 1.6, 95% CI: 1.2-2.2) and in Eskimos (RR = 1.5, 95% CI: 1.2-1.8), while rectal cancer rates did not differ by race/ethnicity. Alaska Natives experienced a 50% higher incidence rate of colorectal cancer overall compared to western Washington whites (RR = 1.5, 95% CI: 1.3-1.6), although rectal cancer rates were similar in the two populations. The highest RR were seen among Alaska Native women; Aleuts and Eskimos had colon cancer rates more than twice that of western Washington white women. No unusual qualitative features were found in the cancers occurring in Alaska Natives. Actuarial colorectal cancer survival rates for Alaska Natives overall were 74% at one year and 42% at 5 years; these rates were very similar to those observed for the western Washington population. Both one and 5-year survival rates showed a significant trend towards improvement over time. CONCLUSIONS: Alaska Natives had substantially higher colorectal cancer incidence rates compared to western Washington whites. Rates were particularly high for Aleut and Eskimo women. These data suggest a need for intensified secondary prevention strategies for this high-risk population, while further research is needed to identify modifiable risk factors.     

Reversible regulation of SHP-1 tyrosine phosphatase activity by oxidation

BACKGROUND AND PURPOSE: Randomized clinical trials testing aspirin in relatively low-risk, middle-aged people have consistently shown small increases in stroke associated with aspirin use. We analyzed the relationship between the regular use of aspirin and incident ischemic and hemorrhagic stroke among people aged 65 years or older participating in the Cardiovascular Health Study. METHODS: We conducted a multivariate analysis of incident stroke rates in a prospectively assessed, observational cohort of 5011 elderly people followed for a mean of 4.2 years. RESULTS: Participants had a mean age of 72 years, and 58% were women. Twenty-three percent used aspirin frequently, and 17% used aspirin infrequently at study entry. Frequent aspirin use was associated with an increased rate of ischemic stroke compared with nonusers (relative risk= 1.6; 95% confidence interval [CI], 1.2 to 2.2; P=0.001). After adjustment for other stroke risk factors, women who used aspirin frequently or infrequently at study entry had a 1.8-fold (95% CI, 1.2 to 2.8) and 1.6-fold (95% CI, 0.9 to 3.0) increased risk of ischemic stroke, respectively (P<0.01, test for trend), compared with nonusers. In men, aspirin use was not statistically significantly associated with stroke risk. Findings were similar when aspirin use in the years before the incident stroke was used in the modeling. Aspirin use at entry was also associated with a 4-fold (95% CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both infrequent and frequent users of aspirin (P=0.003). CONCLUSIONS: Aspirin use was associated with increased risks of ischemic stroke in women and hemorrhagic stroke overall in this elderly cohort, after adjustment for other stroke predictors. The possibility exists of confounding by reasons for aspirin use rather than cause and effect. Whether regular aspirin use increases stroke risk for elderly people without cardiovascular disease can only be determined by randomized clinical trials.     

No increased risk of malignancies and mortality in cyclosporin A-treated patients with rheumatoid arthritis

OBJECTIVE: To evaluate the cyclosporin A (CSA)-attributed risk of developing malignancies in general and malignant lymphoproliferative diseases (LPDs) and skin cancers in particular, as well as the CSA-attributed incidence of mortality in patients with rheumatoid arthritis (RA). METHODS: In a retrospective, controlled cohort study, the incidence of malignancies and mortality was evaluated in 208 CSA-treated patients with RA compared with 415 matched control patients with RA between 1984 and 1995. Patients were followed up for a median of 5.0 years (range 1.4-12.0). RESULTS: Forty-eight cases of malignancy (8 in the CSA group and 40 in the control group; relative risk [RR] 0.40, 95% confidence interval [95% CI] 0.19-0.84) were identified, of which 8 were malignant LPDs (2 CSA versus 6 control; RR 0.67, 95% CI 0.14-3.27) and 14 were skin cancers (2 CSA versus 12 control; RR 0.33, 95% CI 0.08-1.47). Seventy-three patients died (16 CSA versus 57 control; RR 0.56, 95% CI 0.33-0.95) due primarily to cardiovascular diseases (4 CSA versus 22 control; RR 0.36, 95% CI 0.13-1.04) or a malignancy (3 CSA versus 8 control; RR 0.67, 95% CI 0.18-2.43). Proportional hazards regression analysis with correction for potential confounding factors did not significantly change the results. CONCLUSION: The study findings suggest that CSA treatment in RA patients does not increase the risk of malignancies in general or the risk of malignant LPDs or skin cancers in particular. Moreover, the incidence of mortality in CSA-treated RA patients was comparable to that in matched control RA patients.     

Survival and incidence of myocardial infarction in men with ambulatory ECG-detected frequent and complex ventricular arrhythmias. 10 year follow-up of the 'Men born 1914' study in Malm?, Sweden

AIM: To assess to what extent do frequent or complex ventricular arrhythmias, detected during 24 h ambulatory electrocardiographic recording (ECG), influence prognosis with regard to survival and incidence of ischaemic heart disease. METHODS AND RESULTS: The study subjects were the 456 randomly selected men born in 1914, the population-based cohort study of 1982-83, in Malm?, Sweden. The main outcome measures were total mortality and incidence of cardiac event (myocardial infarction and death from ischaemic heart disease). Frequent or complex ventricular arrhythmias (Lown classes 2-5) were detected in 49% of the men with (n = 77), and in 35% of those without, a history of myocardial infarction or angina pectoris at baseline, P = 0.019. Independent of clinically evident coronary artery disease at baseline, and after adjustment for traditional atherosclerotic risk factors and use of digitalis or beta-blocker therapy, frequent or complex ventricular arrhythmias were associated with an increased mortality from ischaemic heart disease (relative risk (RR), 2.1; 95% confidence interval (CI), 1.2-3.9) and an increased cardiac event rate (RR, 1.6; 95% CI, 1.0-2.5)). Men free from both ischaemic-type ST depression and frequent or complex ventricular arrhythmias (used as the control group) had the lowest ischaemic heart disease death rate, 5.9 per 1000 person-years. The combination of ST depression and frequent or complex ventricular arrhythmias was associated with an ischaemic heart disease death rate of 20.9 per 1000 person-years. The cardiac event rate in these two groups was 15.6 and 76.1 per 1000 person-years, respectively (adjusted RR, 2.3; CI, 1.1-4.6). CONCLUSIONS: In elderly men without a history of myocardial infarction and angina pectoris, frequent or complex ventricular arrhythmias during ambulatory ECG recording is associated with an increased incidence of myocardial infarction and mortality. Men who, during ambulatory ECG recording, also demonstrate ST-segment depression have an even less favourable prognosis.     

Relation between the incidence of invasive cervical cancer and the screening interval: is a five year interval too long?

OBJECTIVE: To examine the incidence of invasive cervical cancer per 100,000 women years at risk and relative risk according to screening history among eligible women aged 25-69 in Southampton and South West Hampshire during the three years after completion of the first round of comprehensive screening. RESULTS: There was a significantly higher incidence of invasive cervical cancer in women who had not been screened during the preceding 0.5-5.5 years than in those who had been screened (relative risk (RR) 2.6; 95% confidence interval (CI) 1.6 to 4.3). Among the latter group of women (with interval cancers) there was a significantly higher incidence in those with a long interval of 3.5-5.5 years since their most recent smear than in those with a short interval of 0.5-3.5 years (RR 2.2; 95% CI 1.3 to 3.8). Among women with non-interval cancers, there was a significantly higher incidence among those who had no cytology record than among those who had been screened but were overdue for a smear (RR 3.0; 95% CI 1.2 to 7.3). When screen detected cancers were excluded from the figures the relative risks for all the comparative groups described above were greater, though the 95% confidence limits were wider because the numbers were smaller. The most pronounced difference in incidence was between symptomatic cancers in women with a short screening interval (5.8 per 100,000 women years at risk) and in women with no cytology record (71.3 per 100,000 years at risk). Most cancers were interval cancers (76%) because of the high screening coverage: 89.2% of eligible women aged 25-69 had been screened during the preceding 0.5-5.5 years. The overall incidence per 100000 women years at risk approached that of interval cancers, and was nearer to that observed in the short than the long interval because 74.7% of women had been screened within 3.5 years. CONCLUSION: The results confirm the effectiveness of screening but suggest that a five year screening interval may be too long, at least during the early rounds of screening.     

Pancreas cancer as a second primary malignancy. A population-based study

BACKGROUND: The study of second primary malignancies may give clues to the etiology of various cancers. Little is known about risk factors for pancreatic carcinoma; therefore, its occurrence as a second primary malignancy was investigated. METHODS: Data from the Surveillance, Epidemiology, and End-Results (SEER) program were used for the period from January 1, 1973 through December 31, 1990. Person-years of follow-up for various cancer sites were calculated, excluding the initial 6 months after diagnosis, and were multiplied times the age- and sex-specific incidence rates for pancreas cancer to calculate the expected number of second primary pancreas cancer cases. The observed number of cases was divided by the expected number to estimate the relative risk (RR) of pancreas cancer as a second primary cancer, and 95% confidence limits were calculated. RESULTS: The risk of second primary cancer was elevated after lung cancer for men (RR 1.3, 95% CI 1.0-1.6) and women (RR 2.5, 95% CI 1.9-3.2). An elevation in risk also was found after head and neck cancer in women (RR 1.8, 95% CI 1.2-2.5) and bladder cancer in women (RR 1.5, 95% CI 1.1-2.0), but not in men. Other significant elevations were found after prostate cancer (RR 1.2, 95% CI 1.1-1.3), and a decreased risk was found after lymphoma in men (RR 0.2, 95% CI 0.0-0.8). CONCLUSIONS: Second primary pancreas cancer is increased after tobacco-related malignancies, particularly in females, supporting the role of cigarette smoking as a risk factor for pancreas cancer and suggesting a stronger effect of cigarette smoking for women. The elevation in risk after prostate cancer and the decreased risk after lymphoma in males need to be confirmed in other data sets.     

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.     

Risk factors for early recurrence after ischemic stroke: the role of stroke syndrome and subtype

BACKGROUND and PURPOSE: Information regarding risk factors for early recurrence is limited. Our aim was to identify the clinical predictors of early recurrence after ischemic stroke. METHODS: We prospectively examined 297 patients (mean age, 72.0+/-8.4 years) hospitalized with ischemic stroke to identify recurrent strokes occurring within 90 days of the index stroke. Survival free of recurrence was estimated using Kaplan-Meier analysis stratified by demographic variables; vascular risk factors; stroke syndrome, subtype, vascular territory, and severity; scores on the Barthel Index and Mini-Mental State Examination during hospitalization; blood pressure on admission; and selected laboratory data. We estimated the relative risk (RR) of early recurrence associated with those variables using proportional hazards analysis. RESULTS: We identified 22 recurrent events in the first 90 days after the index stroke, resulting in an early stroke recurrence rate of 7.4%, and death occurred immediately after recurrence in 6 of the 22 patients. A major hemispheric stroke syndrome (RR=2.9; 95% confidence interval [CI]=1.2 to 7.1), atherothrombotic stroke mechanism (RR=3.3; CI=1.3 to 8.3), and atrial fibrillation (RR=2.2; CI=0.8 to 6.1) were independent predictors of early recurrence, after adjustment for demographic variables. Conclusions-Early recurrence was frequent and resulted in increased mortality. Attention to the clinical features of the index stroke, including the presenting syndrome and the ischemic mechanism, and the recognition of atrial fibrillation may help in the selection of patients for the initiation of targeted interventions to prevent early recurrence and subsequent mortality.     

Urbanization and childhood leukaemia in Taiwan

BACKGROUND: In the 1980s socioeconomic development was dramatically rapid in the urbanized municipalities of Taiwan due to a prospering economy. This study addressed the question: Could differences in the incidence of childhood leukaemia (age <15) be demonstrated between urban and rural communities in Taiwan between 1981 and 1990? METHODS: The log-linear regression model was used to assess the effects of age, level of urbanization, and calendar year on the variation of childhood leukaemia incidence rates between 1981 and 1990. RESULTS: Between 1981 and 1990, the overall incidence rate of childhood leukaemia increased by 20% (rate ratio (RR) = 1.2, 95% CI: 1.0-1.5). As compared to rural areas, metropolitan regions showed a significantly higher incidence rate during the study period (RR = 1.3, 95% CI: 1.1-1.6). This urban-rural difference was particularly notable among children <5 years old (RR = 1.5, 95% CI: 1.2-1.9). Dose-response analysis further indicated that risk of childhood leukaemia was monotonically associated with levels of urbanization. The significant gradient in the risk of childhood leukaemia with urbanization was contributed solely by children in the 0-4 years age group. CONCLUSIONS: We noticed a relationship between urbanization and risk of leukaemia in children. Because of a dramatic influx of people into metropolitan areas during the 1980s, our findings may have provided support for the putative association between 'population mixing' or 'population density' and risk of childhood leukaemia. Whether such association can be attributable to virus infection or other aetiologically related leukemogens warrants further investigations.     

Dilation and translation for incomplete sigma-pi neural networks of Hopfield-type--a case study

BACKGROUND: Prior studies evaluating pre-cutting the major papilla to access the bile duct when standard cannulation falls have usually used the needle-knife papillotome. We conducted a prospective study to evaluate the efficacy and safety of an Erlangen-type pre-cut papillotome for pre-cutting. PATIENTS AND METHODS: Three hundred twenty-seven patients (114 men, mean age 67 years) who underwent first-time sphincterotomy at our institution were included. Pre-cutting was performed if free and wire-guided cannulation of the bile duct failed according to an algorithm. RESULTS: Pre-cutting was performed in 123 patients (38%) and selective cannulation was successful in all. Post-ERCP serum pancreatic enzyme levels were more frequently elevated in the pre-cut group (50%) than the non-pre-cut group (27%, p < 0.001); however, there was no difference in the incidence of post-ERCP pancreatitis (pre-cut = 2.7%, 95% CI: 0.66% to 7.6%; non-pre-cut = 1.6%, 95% CI: 0.3% to 4.7%). The incidence of bleeding was similar (pre-cut, 2.4%, non-pre-cut, 3.9%; p > 0.05). CONCLUSION: Pre-cutting the major papilla for biliary access using the Erlangen-type pre-cut papillotome is an effective and reasonably safe procedure when performed by endoscopists with extensive experience in pancreatobiliary endoscopy.