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Biomedical subjects

A Gentile

Publications and source records attributed to A Gentile.

At least 19 recordsLinked to original sources

Effect of amiodarone therapy on mortality in patients with left ventricular dysfunction and asymptomatic complex ventricular arrhythmias: Argentine Pilot Study of Sudden Death and Amiodarone (EPAMSA).

The efficiency of prophylactic antiarrhythmic treatment with amiodarone in reducing 1-year mortality in patients with reduced left ventricular ejection fraction ( < 35%) and asymptomatic ventricular arrhythmias (Lown classes 2 and 4) was investigated in a prospective, multicenter, randomized, controlled study. Among 127 patients who entered the study, 61 were assigned to no antiarrhythmic therapy (control group [CG] and 66 to amiodarone treatment (amiodarone group [AG]). Amiodarone was administered at a dosage of 800 mg/day for 2 weeks followed by 400 mg/day thereafter. A 12-month follow-up was completed for 106 patients (57 in the AG and 49 in the CG). Amiodarone reduced the overall mortality rate, which was 10.5% in the AG versus 28.6% in the CG (odds ratio [OR] 0.29; 95% confidence interval [CI] 0.10 to 0.84; log-rank test 0.02) and sudden death rate, which was 7.0% in the AG versus 20.4% in the CG (OR 0.29; 95% CI 0.08 to 1.00; log-rank test 0.04). Side effects were rare, and in only three patients did amiodarone treatment have to be discontinued.

Aged

[Prognostic value of urokinase-type plasminogen activator and 2 inhibitors PAI-1 and PAI-2 in breast cancer].

It is now clearly established that proteolytic enzymes, and in particular plasminogen activator (uPA), play an important role in breaking down the extracellular matrix, which is considered to be a step in metastasis formation. Plasminogen activators are controlled at various levels. Two inhibitors, PAI-1 and PAI-2, have been identified, the latter being more specific for uPA. In attempts to determine their prognostic value, it is essential to investigate the relative importance of these parameters and their interactions. We used an immunoenzymatic method to assay uPA, PAI-1 and PAI-2 antigens in cytosols prepared from 314 primary breast tumors. The patients were followed up for a minimum of six years and all relevant clinical and laboratory findings had been recorded. Univariate analysis confirmed the poor outcome of patients whose tumors contained large amounts of uPA and PAI-1. In addition, low levels of PAI-2 correlated with shorter disease-free survival in the overall population (P = 0.02), post-menopausal women (P = 0.02) and women without lymph node involvement (P = 0.02). Multivariate analysis using the "Main Effects" Cox model identified node involvement, macroscopic tumor size and PAI-2 as significant variables. The "interactive" Cox model, taking into account interactions between uPA and its two inhibitors, identified a first subgroup with a very poor prognosis associating either high levels of PAI-1 with low levels of PAI-2 in the overall population as well as following stratification for axillary node negative disease, or high levels of uPA with low levels of PAI-2 in the group of menopausal women. We conclude that PAI-1 provides the same prognostic informations as uPA, and does not appear to play its role as an inhibitor. In contrast, PAI-2 increased the prognostic value of both uPA, particularly in post-menopausal women, as well as PAI-1 in a subgroup of axillary node negative patients.

Adult

[Local recurrence after conservative therapy of breast cancer: risk factors, site of recurrence, evolution].

The identification of factors associated with breast recurrence as first event (62 cases, 10%) following conservative surgery and radiation therapy are drawn out from a series++ of 618 mammary carcinomas of clinical size less than 40 mm, stage I and II (UICC), with a median follow up of 8 years. The most powerful predictive characteristic associated with the likelihood of breast recurrence is multiple foci of invasion (42.9% vs 8.9, P = 0.0001, relative risk [RR]: 6). After this rarely cited feature, young age, less than 40 years (20% vs 7.3%, P = 0.0001, RR: 2.8), extensive in situ carcinoma more than 25% (19.2% vs 8.7%, P = 0.003, RR: 2.5) were found also persistent in the Cox model, but not histologic size more than 25 mm (18.9% vs 9.1%, P = 0.01, RR: 2.3). The site of recurrence was studied on the 54 salvage mastectomy done. A high rate of recurrence at distance of the initial site was found: 37% whose more than half, 22%, were multicentric. No significant difference in the mean delay of appearance was noted between recurrence near or at distance of the initial cancer (mean delay 52 months vs 64 months). From the recurrence the evolution is not very favourable: excluding simultaneous metastases found at the preoperative investigation, ten cases, mammary recurrence is followed by a metastatic syndrome in 36% of cases against 17% without it (P = 0.01, RR: 1.9). Metastatic evolution is not significantly linked with the time, early or late, of the mammary recurrence (54.5% before 5 years vs 39% after) but with the association of a controlateral cancer (P = 0.03). Locally ten of the 54 mastectomy presented a thoracic recurrence, often in case of multicentric breast recurrence (P = 0.05) and not significantly when skin or areola were invaded by carcinoma.

Adenocarcinoma

Keratins 6, 13 and 19. Differential expression in squamous cell carcinoma of the head and neck.

One hundred forty-one head and neck squamous cell carcinomas were analyzed for keratin (K) 6, 13 and 19. Staining was evaluated by light microscopy (with or without grading) and image analyzer and expressed as a percentage of positive versus all tumor surface (PSA). Both techniques rendered strongly correlated results. Strong expression was noted in 108 carcinomas (76.1%) for K6, in 18 (12.7%) for K19 and in 21 (14.8%) for K13 (P = .001). One hundred thirty-six (96%) tumors were positive for K6, and their PSA ranged from 0.6% to 48.8%; K19, 48 cases (0.2-44%); K13, 59 (0.2-38.1%). Expression of K6 was related to differentiation. K19 was expressed mainly in moderately and poorly differentiated tumors, and K13 was manifest more in well-differentiated carcinomas or in keratinized areas of less-differentiated ones. Nineteen (13.38%) tumors were positive for both K13 and K19. K19 thus was related to tumor progression and K13 to differentiation. There was no correlation with tumor site or TNM category.

Adult

Family history and the risk of stomach and colorectal cancer.

BACKGROUND: The role of a family history of selected neoplasms in first-degree relatives in the risk of gastrointestinal cancers has been investigated, but requires further quantification. METHODS: A case-control study was conducted in northern Italy on 628 histologically confirmed incident cases of stomach cancer, 766 cases of colon cancer, 456 cases of rectal cancer, and 1766 controls admitted to hospital for acute, nonneoplastic, non-digestive tract disorders. RESULTS: Significant associations were observed between a family history of gastric cancer and stomach cancer risk (relative risk [RR], 2.6), and between a family history of intestinal cancer and colon (RR, 2.4) and rectal cancer (RR, 1.7). There was a tendency for the risks to be above unity for a family history of stomach cancer and for a number of other cancer sites (including esophagus, intestines, liver, pancreas, gallbladder, and lung), and the RR were of borderline statistical significance for cancer of the liver and intestines. The RR for a family history of lung cancer was 1.5 for stomach, 1.2 for colon, and 1.3 for rectal cancer, with none of the estimates being significant. There was no consistent pattern of risk with reference to the type of first-degree relationship; the RR was similar for stomach cancer with reference to parents and siblings, and for colon and rectal cancer, it was only moderately higher with reference to siblings. Significant trends in risk with the number of first-degree relatives were observed for all three cancer sites investigated. CONCLUSIONS: In terms of population attributable risk, approximately 8% of stomach cancers and 3% of colorectal cancers would be related to this familial component.

Aged

Alcohol and epithelial ovarian cancer.

The relationship between alcohol consumption and the risk of epithelial ovarian cancer was analysed using data from a case-control study of 801 histologically confirmed epithelial ovarian cancers and 2114 controls in hospital for acute, non-neoplastic, gynecological, or hormone-related conditions, admitted to a network of teaching and general hospitals in the greater Milan area, northern Italy, i.e. a region with comparatively frequent alcohol consumption by women. Compared to alcohol abstainers, the multivariate relative risks (RRs) were 1.0 [95% confidence interval (CI), 0.7 to 1.4] for less than one, 1.1. (95% CI 0.9 to 1.6) for one to two, 1.2 (95% CI 1.0 to 1.5) for two to three and 1.3 (95% CI 0.9 to 1.8) for three or more drinks per day. A significant direct trend in risk with dose emerged. This finding chiefly derived from an association between ovarian cancer risk and consumption of wine (which accounts for over 90% of alcohol intake in this female population). Although no significant interaction between the effect of alcohol consumption and various women's characteristics emerged, there was a hint that the adverse influence of alcohol consumption is more marked in middle-age and less educated women. Thus, the results of this study suggest that relatively elevated alcohol intake (of the order of 40 g per day or more) may cause a modest increase of epithelial ovarian cancer risk.

Adult

Oral contraceptives and non-contraceptive oestrogens in the risk of gallstone disease requiring surgery.

STUDY OBJECTIVE: The aim was to investigate the relationship between oral contraceptives, non-contraceptive oestrogens, and the risk of gallstone disease requiring surgery. DESIGN: This was a hospital based case-control study carried out between 1987 and 1990. Main outcome measures were frequency of consumption of oral contraceptives and non-contraceptive oestrogens, and the corresponding multivariate relative risk estimates and 95% confidence intervals (CI) in relation to various measures of use of the preparations. SETTING: A network including major teaching and general hospitals in the greater Milan area, northern Italy. SUBJECTS: Subjects were 235 women with gallstones requiring surgery and 538 controls admitted for acute diseases, other than digestive or hormonal diseases or those potentially influencing the use of female hormone preparations. MAIN RESULTS: For oral contraceptives, the relative risk for ever use was 0.8 with 95% CI 0.4 to 1.5. With reference to duration of use, the multivariate relative risk was 1.0 for less than two and 0.5 for two or more years of use. The relative risk was 1.7 (95% CI 0.6 to 4.7) in women who had last used the pill less than five years before diagnosis, but declined to 0.4 (95% CI 0.2 to 1.0) in those who had stopped more than five years before. With reference to oestrogen replacement treatment, the relative risk for ever use was 1.9 (95% CI 1.0 to 3.1). The relative risk, however, was not related to duration of use, since it was 1.8 for less than two and 1.5 for two or more years of use. Relative risk was higher for women who had last used non-contraceptive oestrogens 10 or more years before diagnosis (2.4) than for shorter periods since last use (1.3). CONCLUSIONS: On a clinical and public health scale, oral contraceptives and non-contraceptive oestrogens are unlikely to have an important influence in the aetiology of gallbladder disease.

Adult

Anthropometric indicators of endometrial cancer risk.

The relation between selected anthropometric indicators and the risk of endometrial cancer was evaluated using data from a case-control study conducted in Northern Italy on 562 cases and 1780 controls in hospital for acute, non-neoplastic or hormone-related disease. There was no appreciable association between height and endometrial cancer: compared with the lowest quintile, the multivariate relative risks (RR) were 0.9, 0.9, 0.7 and 0.8 for each subsequent quintile. Weight was directly associated with risk (RR = 2.7 for top vs. bottom quintile), and the positive association was even stronger when indices of body mass which make allowance for height were considered: the relative risks for extreme quintiles were 3.4 for W/H2 (Quetelet's index, weight and height), 3.8 for W/H1.5 and 3.5 for W0.33/H. Surface area, which was positively correlated both with height and weight, showed a weaker direct association (RR = 2.4 between extreme quintiles). The relations with measures of body weight were apparently stronger in postmenopause, but the point estimates for the upper quintile were also around 2 in premenopausal women. Although the major findings of this study are not new, they provide more detailed information that was hitherto available on the relation between various anthropometric indicators and endometrial cancer risk. In relation to height, with the sample size of this study it was possible to exclude, at the conventional 95% probability, relative risks above 1.0 for the fourth and above 1.1 for the fifth as compared with the lowest quintile. This provides indirect evidence against the hypothesis that nutritional status early in life is related to the subsequent development of endometrial cancer.

Adult

Relationship between cathepsin D, urokinase, and plasminogen activator inhibitors in malignant vs benign breast tumours.

The concentrations of cathepsin D (Cath D), urokinase (uPA) and two plasminogen activator inhibitors (PAI-1 and PAI-2) were analysed in the cytosols of 130 human mammary tumours (43 benign tumours and 87 primary and unilateral breast carcinomas). uPA, PAI-1 and PAI-2 levels were measured by antigenic immunoassays and Cath D by immunoradiometric assay. The median levels of the four parameters were significantly higher in the malignant tumours than in the benign ones. Cath D and uPA increases were 4-fold and 5-fold respectively. PAI-1 and PAI-2 increases were much more important, 74-fold and 29-fold respectively. In malignant tumours, median levels of Cath D and uPA did not vary according to classical prognostic factors (histologic grade, presence or absence of axillary lymph nodes, steroid receptors, UICC stage, tumour size, age, and menopausal status). However, PAI-1 decreased in ER+ and PR+ tumours and PAI-2 increased in menopausal women's tumours. When Cath D, uPA, PAI-1 and PAI-2 levels in malignant tumours were compared, positive correlations were found for all combinations. The implication of plasminogen activator inhibitors in the phenomenon was surprising and merits further investigation using tools other than global antigen measurements in tumours.

Breast Diseases

Steroid myopathy: clinical and immunohistochemical study of a case.

A 42 year old woman with foot process disease, was treated with corticosteroids for 6 years. She had been suffering, for about 3 years from progressive muscle weakness of the limbs, accompanied by general paresthesia, cramps of the calves and burning muscle pain both at rest and an effort. The clinical, neurophysiological and histochemical examination indicated noninflammatory myopathic damage. The progressive reduction of corticosteroid dosage led rapidly to a distinct improvement, but not to a remission, of symptoms. Clinical and laboratory findings were consistent with those observed in most cases of steroid myopathy described in literature. We discuss the possible pathogenetic role of corticosteroids in this affection.

Adult

Association between certain foods and risk of acute myocardial infarction in women.

STUDY OBJECTIVE: To examine the relation between selected foods and acute myocardial infarction in women. DESIGN: Case-control study conducted over five years. SETTING: 30 Hospitals with coronary care units in northern Italy. SUBJECTS: 287 Women who had had an acute myocardial infarction (median age 49, range 22-69 years) and 649 controls with acute disorders unrelated to ischaemic heart disease (median age 50, range 21-69 years) admitted to hospital during 1983-9. MAIN OUTCOME MEASURES: Frequency of consumption of various foods and odds ratios of risks associated with these foods. RESULTS: The risk of acute myocardial infarction was directly associated with frequency of consumption of meat (odds ratio 1.5 for upper v lower thirds of consumption), ham and salami (1.4), butter (2.3), total fat added to food (1.6), and coffee (2.8). Significant inverse relations were observed for fish (0.6), carrots (0.4), green vegetables (0.6), and fresh fruit (0.4). The risk was below one for moderate alcohol consumption (0.7) and above one for heavier intake (1.2). Allowance for major non-dietary covariates, including years of education, smoking, hyperlipidaemia, diabetes, hypertension, and body mass index, did not appreciably alter the estimates of risk for most of the foods; for coffee, however, the odds ratio fell to 1.8 on account of its high correlation with smoking. CONCLUSIONS: The frequency of consumption of a few simple foods may provide useful indicators of the risk of myocardial infarction. Furthermore, specific foods such as fish, alcohol, or vegetables and fruits may have an independent protective role in the risk of cardiovascular diseases.

Adult

Height and cancer risk in a network of case-control studies from northern Italy.

The relationship between self-reported height and cancer risk was investigated in an integrated series of case-control studies including 273 cases of cancer of the oesophagus, 474 of the stomach, 558 of the colon, 352 of the rectum, 227 of the liver, 267 of the pancreas, 110 of the larynx, 2,388 of the breast, 545 of the cervix uteri, 563 of the endometrium, 688 of the ovary, 80 of the prostate, 263 of the bladder, 105 of the kidney, 43 Hodgkin's disease, 152 non-Hodgkin's lymphomas, 109 multiple myelomas, and a total of 5,574 controls admitted to hospital for acute, non-neoplastic conditions. No significant positive trend in risk was observed for any of the cancer sites considered, and some suggestion of elevated risks for the upper quintile of height was observed only for prostate (relative risk, RR = 1.4), kidney (RR = 2.7) and colon (RR = 1.2) in males (but not in females). For breast cancer, all the RRs for subsequent quintiles of height were close to unity. Four neoplasms showed significant inverse trends with height: oesophagus (RR = 0.7 for highest vs. lowest quintile), cervix (RR = 0.4), endometrium (RR = 0.7) and ovary (RR = 0.6). For oesophagus and cervix the trends could be explained, at least in part, in terms of social class correlates (multivariate RR 0.8 and 0.5, respectively), while for endometrium they could possibly be related to an inverse correlation between height and body mass (multivariate RR 0.9). Thus, our study did not support the hypothesis that nutrition in childhood and adolescence (which in this population is a determinant of adult height) is directly related to the subsequent risk of cancer at several major cancer sites. A number of inverse associations emerged, which may be either spurious and incidental, or suggest that poorer nutrition early in life may be an unfavourable indicator of the subsequent risk of selected neoplasms.

Adult

A computerized respiratory sinus arrhythmia program for the non-invasive assessment of parasympathetic activity.

The availability of sophisticated signal analysis methods based on the use of micro-computers allows an accurate non-invasive assessment of parasympathetic activity, through the measurement of the respiratory sinus arrhythmia. The program described herein is in Quickbasic and consists of 5 programs. At termination of the computer analysis the results are printed which include the average heart rate for inspiration and expiration, the averaged standard deviation of the R-R intervals for inspiration and expiration, and the R-R interval in milliseconds averaged for all inspiratory and expiratory cycles. Significant correlations were obtained when comparing the analyses of the computerized program with a manual method.

Analog-Digital Conversion

Salt preference and the risk of gastrointestinal cancers.

The relationship between the consumption of salt and the risk of gastrointestinal cancer was examined using data from a case-control study conducted in northern Italy. The study was conducted on 526 incident cases of gastric cancer, 621 of colon cancers, 382 of rectal cancers, and 1,223 controls admitted to hospital for acute, nonneoplastic, nondigestive tract disorders. Compared with those for people with low salt intakes, the relative risks (and 95% confidence intervals) for those with intermediate and high salt intakes were 1.3 (1.0-1.8) and 1.2 (0.8-1.7) for stomach, 1.0 (0.8-1.3) and 1.1 (0.8-1.5) for colon, and 1.2 (0.9-1.6) and 0.9 (0.6-1.3) for rectum. None of the trends in risk were statistically significant, and the risk estimates were not materially modified by allowance for major identified potential confounding factors. Thus, this study gives little support to the existence of any strong association between salt intake and gastrointestinal cancers. However, in view of the results obtained and of the uncertainties of salt intake measurement, the possibility exists of a real, although moderate, association of salt intake with gastric cancer.

Adult

Gastrointestinal activities of a new pirenzepine-analog, nuvenzepine, in the cat.

Nuvenzepine, a new pirenzepine-analog, administered intraduodenally, displayed a long-lasting and dose-dependent inhibition of neostigmine-induced intestinal motility in anaesthetized cats. On ileal motor activity, the compound showed a potency 10 times greater than that of pirenzepine, and, although to a lesser extent, it was also active, unlike pirenzepine, on colonic stimulated motility. Furthermore, in conscious cats, nuvenzepine inhibited pentagastrin-stimulated gastric acid secretion resulting 25-30 times more potent than pirenzepine. The observed differences between antisecretory and antispastic activities displayed by nuvenzepine and pirenzepine suggest that the new pirenzepine-analog may act on gastrointestinal functions through an additional non-anticholinergic mechanism.

Animals

Reproductive and menstrual factors and risk of colorectal cancer.

The relation between reproductive and menstrual factors and the risk of colorectal cancer was investigated in a case-control study conducted in Northern Italy on 279 women with colon cancer, 153 with rectal cancer and 386 controls admitted to hospital for a wide spectrum of acute, nonneoplastic, nondigestive disorders. Compared with nulliparous women, the relative risks (RR) of colon cancer were 1.1 for one and two births, 1.3 for three or four, and 1.1 for five or more. Corresponding values for rectal cancer were 0.9 for one, 1.1 for two, 1.4 for three or four, and 0.8 for five or more births. No significant association emerged with number of abortions, and no consistent pattern of trends for both colon and rectum cancer was observed in relation to age at first or last birth. Women whose menarche occurred at age 15 or over were at significantly lower risk of colon cancer (RR 0.5, 95% confidence interval = 0.3-0.9), and the point estimate was below unity, though nonsignificantly, for rectal cancer too (RR = 0.7). There was no relation between age at menopause, duration of menstrual cycles, and cancers of the colon and rectum. The present study produced no evidence that reproductive factors are related to colorectal cancer in this population. With this sample size, it was possible to exclude relative risks below 0.8 for colon and 0.7 for rectal cancer among multiparous women versus nulliparous ones. These findings are thus inconsistent with the epidemiological evidence on reproductive and menstrual factors and breast cancer in this and other populations, with the sole potential exception of the reduced risk of colorectal cancer among women whose menarche occurred at age 15 or over.

Adult

Relation between primary tumor shape and biological behavior in breast cancer.

The aim of this study was to investigate the biological significance of tumor shape in breast cancer by considering the shape not as a casual event but as an expression of the behavior and natural history of the tumor. The shape was studied by an analytical morphometry procedure and was related to axillary metastases, which up to now are the most meaningful prognostic factors in this disease. Fifty cases of infiltrating breast carcinoma (25 N+ and 25 N-) were investigated. The shape, studied on subgross sections of the tumor, was considered as the result of two components: the subtle contour irregularities and the main distortions of the figure. The procedures used allowed us to distinguish and to parametrize these two components in order to submit them to univariate analysis (Student's t test), a principal components analysis and, finally, a multivariate discriminant analysis (Hotelling test). The utilized analytical procedures by work-station S.A.M. (S.A.M. work station is a product of "Metamorphosis") consisted of three steps: 1) Extraction of tumor function curve obtained by Kth order polynominals which gives a smoothing effect to the original curve; 2) Evaluation of contour irregularities by Fourier harmonic analysis; 3) Evaluation of shape asymmetry by SAE (shape asymmetry evaluator). We considered also the roundness factors of the original and function curves and finally the maximum tumor diameter. Three parameters relating to contour irregularities (sum and mean value of Fourier harmonic amplitude and percentage of superimposed points) and parameters relating to main distortions of the figure (mean value of SAE) were highly significant (p less than 0.001). The roundness factor of the original curve was more significant (p less than 0.001) than that of the function curve (p less than 0.01) whereas maximum tumor diameter was not significant when tested by Student's t test. Multivariate discriminant analysis allowed 20% of error to be reached by using 3 parameters relating to the shape analysis and the two roundness factors. By using 8 parameters, including maximum tumor diameter, the percentage error was 16%. The results obtained, while they stress the usefulness of the employed procedure, reveal that shape of the tumor, together with its dimensions, is an important expression of the biological behavior relating to metastatic spread.

Analysis of Variance