Hospital Control Subjects Research Articles

Risk Factors for Epithelial Ovarian Tumours of Borderline Malignancy

A case-control study was conducted on 91 cases with histologically-confirmed borderline ovarian tumours and 237 control subjects in hospital for acute non-gynaecological, hormonal or neoplastic disease. Women reporting three or more births, compared to nulliparae, had a relative risk (RR) estimate of 0.6, but this finding was not statistically significant (95% confidence interval (CI): 0.2-1.4). The risk of borderline tumours increased, although not significantly, with later age at first birth: compared to women reporting first birth at age 24 or before, the RRs were 1.3 and 1.7 in those reporting respectively their first birth at age 25-29 and 30 years or more. No significant relationship emerged between borderline ovarian cancer and age at menarche, menopausal status and lifelong menstrual pattern. Cases tended to report a later age at menopause than controls, but the trend in risk was not statistically significant. Nine cases (9.9%) and 68 controls (24.9%) reported oral contraceptive use: compared with never users the multivariate RR for ever users was 0.3, and the risk dropped with duration of use to 0.2 in users for two years or more (chi 2 (1) trend = 12.70, p less than 0.001). This study provides epidemiological evidence of a pathogenetic continuum between borderline and invasive ovarian tumours.

Role of alcohol in recurrences of atrial fibrillation in persons

The role of alcohol in recurrences of atrial fibrillation (AF) was assessed in a consecutive series of 98 patients (75 men) aged <65 years. In addition to etiologic assessment using clinical and laboratory methods and echocardiography, the patients' drinking habits were evaluated by recording the amount of alcohol used during the week preceding AF, by responses to the CAGE (Cut, Annoying, Guilt, Eye; see below) questionnaire (a screening test for alcohol abuse) and by selected laboratory tests. Two groups of control subjects were studied: 98 sex- and age-matched patients admitted to the emergency ward for acute illnesses, and SO subjects selected randomly from the local out-of-hospital population. The mean alcohol consumption among men during the study week was 186 g (median 45 g; range 0 to 2,100 g) among patients, whereas among male hospital and population control subjects it was 86 g (30 g; 0 to 1,050 g) and 94 g (35 g; 0 to 630 g), respectively. When the weekly alcohol consumption was analyzed in 3 categories (0; 1 to 210 g; >210 g), there was a significant difference between AF cases and hospital control patients (p = 0.03), but not between AF cases and population control subjects. Multivariate analysis of data of AF cases and population control subjects showed that alcohol intake and a positive response to 1 or more of the CAGE questions were independently related to AF in men. Other independent risk factors were the presence of heart disease, low serum potassium and lack of sleep or experience of excess psychologic stress, or both. These results indicate that alcohol consumption is an independent risk factor for recurrences of AF in men of working age.

Type of cigarettes and cancers of the upper digestive and respiratory tract

The relationship between type of cigarettes smoked and the risk of cancer of upper digestive and respiratory sites was investigated in a case-control study conducted in Northern Italy on 291 males with cancer of the oral cavity or pharynx, 288 with cancer of the esophagus, 162 with cancer of the larynx, and 1,272 control subjects in hospital for acute conditions unrelated to tobacco or alcohol consumption. Using a distinction based on tar-yield or the brand smoked for the longest time (less than 22 mg, low to medium tar; greater than or equal to 22 mg, high tar), the multivariate relative risks among ever-smokers were 8.5 for low/medium and 16.4 for high tar cigarettes for oral and pharyngeal neoplasms, 3.3 and 7.8 for esophageal, and 4.8 and 7.1 for laryngeal cancers. The differences according to type of cigarettes were similar in proportional terms, and hence larger in absolute terms, when analysis was restricted to current smokers only. Thus, these data provide further quantitative evidence on the importance of type of cigarette smoked on the risk of upper-digestive and respiratory tract cancers and have important public health implications.

Reproductive factors and the risk of invasive and intraepithelial cervical neoplasia.

The relation between reproductive factors and cervical neoplasia was evaluated in a case-control study of 528 cases of invasive cancer compared with 456 control subjects in hospital for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer, and of 335 cases of cervical intraepithelial neoplasia compared with 262 outpatient controls. The risk of invasive cervical cancer increased with number of livebirths, the estimated multivariate relative risk (RR) being 4.39 in women with five or more births compared with nulliparous women. There was also an inverse relation with age at first livebirth (RR = 0.42 for greater than or equal to 30 vs. less than 20 years) which, however, disappeared after inclusion of parity in multiple logistic regression analysis. Likewise, cases of invasive cervical cancer tended more frequently to report induced abortions. However, this association was not statistically significant after allowance for confounding factors, including parity. No relation emerged with number of spontaneous abortion and age at last pregnancy. When the interaction between parity and sexual habits was analysed, the relative risk increased in subsequent strata of parity with increasing number of sexual partners or decreasing age at first intercourse, thus suggesting an independent effect of sexual and reproductive factors, and hence multiplicative on the relative risk of invasive cervical cancer. No consistent association emerged between the risk of intraepithelial cervical neoplasm and parity, number of abortions and age at first or last birth.

Hydralazine use in relation to cancers of the lung, colon, and rectum.

It has been suggested, based on animal experiments and limited human data, that the anti-hypertensive drug hydralazine might be carcinogenic, and among the sites of concern are the lung and colon. To assess the possible relationship between the use of hydralazine and lung and colorectal cancers in humans, we compared 1006 cases of lung cancer with 3531 hospital control subjects, and 972 cases of colorectal cancer with 3276 controls. Data were collected by interview in hospitals in the United States and Canada. Overall, 1.1% of the lung cancer cases, 1.6% of the colorectal cancer cases, and 1.5% of the controls had used hydralazine. Compared with those who had never used hydralazine, the relative risk estimate of lung cancer for those who first took the drug at least 18 months before hospital admission was 1.1 (95% confidence interval 0.4-2.9). The estimate for use for at least 1 year was 1.4 (0.5-3.8) and for use for at least 5 years the estimate was 0.9 (0.2-4.3). The corresponding relative risk estimates for colorectal cancer were 1.2 (0.5-2.5) for any use, 1.7 (0.8-3.7) for use for at least one year, and 2.4 (0.8-6.9) for five or more years of use. Other antihypertensive treatments and risk factors, including cigarette smoking in the analysis of lung cancer, were taken into account in these estimates. Although the effect of use after long latent intervals could not be evaluated, the results provide no support for the hypothesis that hydralazine use increases the risk of lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors in lacunar syndromes: a case-control study.

The association between some hypothetical risk factors (previous TIA, hypertension, ECG ischemic abnormalities, diabetes, cigarette smoking, atrial fibrillation, hypercholesterolemia, hypertriglyceridemia, high hematocrit) and lacunar syndromes has been evaluated by a matched sample case-control study involving 108 consecutive, incident cases with lacunar syndrome and 216 hospital control subjects, matched for sex and age. A significant increase of Relative Risk (RR) has been shown for: 1. Previous history of TIA; 2. Hypertension; 3. Smoking; 4. Diabetes. No relevance was shown for: 1. Atrial fibrillation; 2. Hypercholesterolemia; 3. Hypertriglyceridemia; 4. High hematocrit. The analysis of the triplets of subjects (1 case + 2 controls) without hypertension showed a significant RR increase for: 1. Previous history of TIA; 2. Ischemic cardiac abnormalities; 3. Atrial fibrillation. Such findings support the hypothesis that, in a minority of cases with lacunar syndrome, the pathogenetic mechanism could be different from occlusion of penetrating arteries in hypertensive patients.

A case-control study of diet and gastric cancer in northern Italy.

Dietary factors in the aetiology of stomach cancer were investigated using data from a case-control study conducted in Northern Italy on 206 histologically confirmed carcinomas and 474 control subjects in hospital for acute, non-digestive conditions, unrelated to any of the potential risk factors for gastric cancer. Dietary histories concerned the frequency of consumption per week of 29 selected food items (including the major sources of starches, proteins, fats, fibres, vitamins A and C, nitrates and nitrites in the Italian diet) and subjective scores for condiments and salt intake. Pasta and rice (the major sources of starch), polenta (a porridge made of maize) and ham were positively related with gastric cancer risk, whereas green vegetables and fresh fruit as a whole (and specifically citrus fruit) and selected fibre-rich aliments (such as whole-grain bread or pasta) showed protective effects on gastric cancer risk. Allowance for major identified potential distorting factors (chiefly indicators of socio-economic status) reduced the positive association with pasta or rice consumption, but did not appreciably modify any of the other risk estimates. When a single logistic model was fitted including all food items significant in univariate analysis, the 3 items remaining statistically significant were green vegetables (relative risk, RR = 0.27 for upper vs. lower tertile), polenta (RR = 2.32) and ham (RR = 1.60). Indices of beta-carotene and ascorbate intake were negatively and strongly related with gastric cancer risk, but the association with these micronutrients was no longer evident after simultaneous allowance for various food items. An approximately 7-fold difference in risk was found between extreme quintiles of a scale measuring major positive and negative associations.

Nonspecific inflammatory bowel disease and smoking.

The authors assessed the relation between cigarette smoking and nonspecific inflammatory bowel disease in a case-control study of 124 cases of ulcerative colitis, 109 cases of Crohn's disease, and 250 age- and sex-matched control subjects in hospital for acute nongastric or intestinal conditions unrelated to smoking. For ulcerative colitis, the risk for current smoking compared with never smoking was 0.5, with a 95% confidence interval (Cl) of 0.3-1.0. They observed decreasing risk with increasing number of cigarettes smoked. The risk for ex-smokers, however, was greater than that for never smokers (relative risk = 2.7; 95% Cl = 1.5-4.9). The elevated risk of ulcerative colitis in ex-smoking in the presence of an overall lack of association with ever-smoking may plausibly be attributed to either 1) brief induction time of a protective effect of smoking on ulcerative colitis or 2) selective cessation of smoking due perhaps to very early symptoms of the disease. If time at first onset of bowel symptoms, instead of clinical diagnosis, is considered as the index date, the negative association between ulcerative colitis and current smoking would have weakened in men and disappeared in the overall series. There was clear evidence of a positive association between cigarette smoking and Crohn's disease (relative risk for ever smokers vs. never smokers = 4.0; 95% Cl = 2.2-7.3). The risk estimates increased with the number of cigarettes smoked per day and duration of habit. The association between current smoking and Crohn's disease was even stronger when age at first onset of bowel symptoms was considered as the index date, but the risk for ex-smokers fell below unity.

Hydralazine and Breast Cancer2

Hydralazine (CAS: 86-54-4; 1-hydrazinonaphthalazine) is a well-established antihypertensive agent. There are no conclusive data on the drug as a human carcinogen, but one of its metabolites, hydrazine (CAS: 302-01-2), has been shown to be carcinogenic in rats and mice. To assess the relationship of hydralazine to human breast cancer, 3,419 women with breast cancer and 3,219 hospital control subjects were studied. Data were obtained by interview in hospitals in the United States and Canada. A total of 1.4% of the cases and 1.2% of the controls had used hydralazine. Compared with never use, the relative risk (RR) estimate for hydralazine that was first used at least 18 months before admission was 0.9 [95% confidence interval (CI), 0.5-1.7] after risk factors for breast cancer and the use of other antihypertensive drugs and diuretics were taken into account by multivariate analysis. The RR estimate for hydralazine use lasting at least 1 year was 0.9 (95% CI, 0.5-1.7). RR estimates for longer durations of use (up to 5 or more yr), and for use within strata of risk factors for breast cancer, were close to 1.0. The results suggest that hydralazine does not increase the risk of breast cancer in humans in the short term. Whether the risk is increased after latent intervals of many years could not be evaluated.

Sexual factors, venereal diseases, and the risk of intraepithelial and invasive cervical neoplasia.

The relation between major indicators of sexual habits (age at first intercourse and total number of sexual partners), history of selected venereal diseases, and cervical neoplasia was investigated using data from a case-control study of 206 cases of cervical intraepithelial neoplasia compared with 206 age-matched outpatient controls, and of 327 cases of invasive cancer compared with 327 control subjects in hospital for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer. The relative risks increased with decreasing age at first intercourse and increasing number of sexual partners both for intraepithelial and for invasive cancers. The effects of these two variables were independent, since they were only marginally affected by reciprocal adjustment, or by allowance for several other identified potential distorting factors. The negative association with age at first intercourse was particularly strong in the case of invasive cancers, with risk estimates over five-fold elevated for women reporting their first intercourse before age 18 compared with those aged over 22 years. This relation might be discussed in terms of multistage models of carcinogenesis, which predict that the incidence of epithelial carcinomas is a function of duration of exposure. In fact, when age was allowed for, the relative risks of cervical neoplasia were positively and strongly related with the total duration of the interval between age at diagnosis/interview and age at first intercourse. Clinical histories of several sexually transmitted diseases were positively associated with the risk of intraepithelial neoplasia. In particular, genital warts were reported by nine cases but no control subject. No such association, however, emerged for invasive carcinomas. Thus, the current findings confirm that, although intraepithelial neoplasia and invasive cervical cancer appear to share several important epidemiological features, the specific (infectious) agents implicated in dysplastic lesions probably differ to some extent from those causing invasive cancer.

Limitations of 24-hour intraesophageal pH monitoring in the hospital setting

Prolonged intraesophageal pH monitoring is considered by some to be the most sensitive and specific test of gastroesophageal reflux. We prospectively examined the ability of the test to discriminate 64 hospitalized patients with typical reflux symptoms from 20 age-matched hospitalized control subjects. Patients were subdivided based on endoscopic findings into two groups: group 1, normal endoscopy (n = 30); group 2, erosive esophagitis (n = 34). Six different individual reflux variables and a scoring system were evaluated. Total esophageal acid exposure time and the number of reflux episodes requiring longer than 5 min to clear were each found to have greater discriminatory power than other variables and the scoring system. Although the 64 patients had significantly more acid reflux than controls, only 48% had abnormal results (defined as 2 SD from the control mean). Group 1 patients had significantly more reflux than controls, though only 21% had abnormal results. Group 2 patients were significantly different than both controls and group 1, but 29% had normal studies. Ninety-three percent of the group 1 patients with normal studies responded to antireflux therapy, and only 1 patient had another explanation for the symptoms. The finding that 24-h pH monitoring was normal in half of the individuals presenting with reflux symptoms and in 29% of the patients with erosive esophagitis indicates that negative test results must be interpreted with caution. The insensitivity of the test may relate to the manner in which the study has traditionally been performed in the hospital, and outpatient ambulatory monitoring may improve its reliability.

Memory for recent U.S. presidents in patients with cerebral disease.

Four tasks were developed to assess memory for recent U.S. presidents: free recall of presidents' names, naming their photographs, and temporal ordering of their printed names and photographs. The tasks were standardized on a sample of 250 hospital control subjects and administered to 55 patients with cerebral disease. Recall of the presidents' names, a task frequently advocated for mental status examination, was relatively difficult for hospital control patients and was least sensitive to brain disease. None of the brain-damaged patients manifested an isolated retrieval defect. Generalized memory impairment for recent presidents was not found with focal lesions. In the context of a diffuse or bilateral disease, generalized memory impairment for recent presidents was a frequent concomitant of substantial intellectual loss. This brief, multi-task assessment of memory for recent presidents may prove a more useful adjunct to neurobehavioral evaluation than testing simple recall of presidents' names.

"PAP" SMEAR AND THE RISK OF CERVICAL NEOPLASIA: QUANTITATIVE ESTIMATES FROM A CASE-CONTROL STUDY

The relation between Papanicolau ("Pap") smear and the risk of cervical neoplasia was evaluated in a case-control study in which 145 women with cervical intra-epithelial neoplasia (CIN) were compared with 145 age-matched outpatient controls, and 191 cases of invasive cervical cancer were compared with 191 control subjects in hospital for acute conditions unrelated to any of the established or suspected risk factors for cervical cancer. Compared with women with no previous screening smear, the relative risk (RR) estimate for invasive cancer was 0·44 (with 95% confidence interval [CI]=0·24-0·80) for those who had had one smear and 0·20 (95% CI= 0·13-0·32) for those who had had two or more smears. The corresponding estimates for CIN were 0·27 (95% CI=0·10-0·71) and 0·12 (95% CI = 0·06-0·25), respectively. The risk estimates for intervals of more than 5, 3-5, and less than 3 years were 0·36, 0·18, and 0·10 for invasive cancer, and 0·45, 0·31, and 0·07 for CIN. These results were not materially modified by adjustment for the major risk factors for cervical cancer, such as indicators of socioeconomic status and sexual habits. According to the estimates of this study, 64% of invasive cervical cancers could be prevented by screening at intervals of more than 5 years, an additional 18% by reducing the interval to 3-5 years, and a further 8% to less than 3 years.

Estrogen use and breast cancer interaction with body mass

With few exceptions, most epidemiologic studies do not show an excess relative risk of breast cancer associated with menopausal estrogen therapy. Other studies show a relationship of breast cancer to obesity, which is characterized by increased endogenous estrogen production. This study explored the possibility of an interaction between ponderosity and exogenous estrogen use in a case-control study of 113 postmenopausal breast cancer patients and pair-matched hospital control subjects. In this series, neither menopausal estrogen use nor relative weight were significantly associated with breast cancer risk. However, among estrogen users, the relative risk of breast cancer was strikingly influenced by the ponderosity of the subjects; the relative risk was 0.41 for women whose relative weight was less than the median, compared with 1.29 for those whose relative weight exceeded the median. The mean age was also examined at diagnosis in order to explore the potential of exogenous estrogen as a tumor promotor. The mean age at breast cancer diagnosis in estrogen users, 58.1 years, was significantly lower than in nonusers, 63 years. A significant linear relationship was found between age at diagnosis and body weight among estrogen users. Estrogen-treated women in the lowest tertile of body weight had the diagnosis of breast cancer made seven years earlier than those in the highest tertile of weight. There was no significant difference in the distribution of clinical stages at diagnosis between estrogen users and nonusers. These data suggest that relative body weight is an important modifier of the effect of exogenous estrogens on breast cancer biology.

Breast cancer and estrogen replacement therapy

Concern over the possible effect of estrogen replacement therapy on the subsequent development of breast cancer prompted us to compare 199 postmenopausal breast cancer patients with 451 hospital control subjects and 852 community control subjects on their prior use of estrogens. Estrogen use did not increase the breast cancer risk for women with a surgical menopause. Among women with a natural menopause, estrogens administered by all routes were associated with breast cancer risks of 1.7 or 1.8. There was no coherent pattern of changing risks with varying durations of use, different daily dosages, years since first use of estrogen, or years since most recent use. When women who usually received estrogen by injector were excluded, the risk estimates for oral estrogens were 1.3 (case subjects compared to community control subjects) and 1.2 (case subjects compared to hospital control subjects). These increases were not statistically significant. Use of injectable estrogens produced a fourfold increase in breast cancer risk among naturally postmenopausal women.

Noncontraceptive Estrogens and Myocardial Infarction in Young Women

The effect of noncontraceptive estrogens on the risk of myocardial infarction (MI) in women aged 30 to 49 years was investigated in 477 women with first infarctions and in 1,832 hospital control subjects. There was little evidence of an effect: overall, the estimated relative risk of acute MI for women who had used noncontraceptive estrogens in the preceding month, after allowance for potential confounding factors, was 1.0 (95% confidence intervals, 0.6 to 1.7); the corresponding estimate for women who had discontinued use more than one month previously was 1.2 (0.8 to 1.8). There was also no apparent association in various subgroups, including women who smoked heavily and those who had no identified predisposition.

Noncontraceptive estrogens and myocardial infarction in young women

The effect of noncontraceptive estrogens on the risk of myocardial infarction (MI) in women aged 30 to 49 years was investigated in 477 women with first infarctions and in 1,832 hospital control subjects. There was little evidence of an effect: overall, the estimated relative risk of acute MI for women who had used noncontraceptive estrogens in the preceding month, after allowance for potential confounding factors, was 1.0 (95% confidence interval, 0.6 to 1.7); the corresponding estimate for women who had discontinued use more than one month previously was 1.2 (0.8 to 1.8). There was also no apparent association in various subgroups, including women who smoked heavily and those who had no identified predisposition. (<i>JAMA</i>244:339-342, 1980)

Suppressor Cells in Immunodepressed Bladder and Prostate Cancer Patients

Peripheral blood lymphocytes from 23 patients with bladder and prostate cancer were tested for their ability to respond in vitro to phytohemagglutinin, concanavalin A and allogeneic cells. The lymphocyte response was depressed in 15 patients (65 per cent), 13 with advanced disease, compared to peripheral blood lymphocytes from age-matched hospitalized control subjects tested on the same day. Furthermore, the hyporesponsive lymphocytes from 11 of the 15 cancer patients (73 per cent) inhibited the phytohemagglutinin, concanavalin A and mixed lymphocyte culture reactivity of normal lymphocytes in co-cultures (16 to 78 per cent suppression). In contrast, lymphocytes from control donors caused no suppression. Incubation of the patients’ unseparated peripheral blood lymphocytes on plastic to remove adherent cells restored lymphocyte responsiveness and eliminated their suppressor activity. Returning the adherent cells to cultures with patients’ autologous separated and normal lymphocytes recaptured the suppressive effect. Pre-incubation of the patients’ lymphocytes with concanavalin A markedly enhanced their ability to suppress and induced moderate suppressor activity by normal lymphocytes. These data suggested that 1 mechanism for the depression of cell-mediated immunity seen in patients with advanced urological cancer may be owing to non-specific suppressor cells, possibly monocytes.

Intrauterine contraceptive device use and pelvic inflammatory disease

We examined the relationship between use of IUD's and PID, based on 44 women who were admitted to hospitals with first episodes of PID and 259 hospital control subjects. All the women used either IUD's or oral contraceptives. The age-adjusted relative risk for those using IUD's at the time of admission was 6.5 (95% confidence interval, 3.2 to 13.0). The association remained when several variables, and particularly parity, were taken into account. There was a suggestion that users who had had an IUD in place for at least 5 years had a higher risk of PID than did users of shorter duration. The data also suggest that copper-containing IUD's may be safer than other devices.

Plasma catecholamines, stress and aggression in maximum security patients

Investigations into the stress response of patients committed to a special hospital for criminally deviant offences have identified a group of sympathetically hypoactive patients who excrete more noradrenaline and less adrenaline in the urine than either the remaining hospital population or control subjects, during conditions of stresser anticipation. Further investigation of these patients has shown that similar differences in plasma catecholamines exist, and that the group of patients characterised by this imbalance tend to have been committed for the most physically violent crimes.