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Biomedical subjects

L Garfinkel

Publications and source records attributed to L Garfinkel.

At least 19 recordsLinked to original sources

Mortality hazard associated with prescription hypnotics.

BACKGROUND: The American Cancer Society's Cancer Prevention Study II was a large survey designed primarily to examine cancer risks such as cigarette smoking. From the same survey and methods, data on usage of "prescription sleeping pills" in 1982 were examined. METHODS: Standardized mortality ratios were computed. Because sleeping pill use could be a proxy for other risk factors, cox proportional hazards models were computed to control for possible confounding factors as extensively as the data permitted. RESULTS: Men and women who reported taking prescription sleeping pills 30+ times in the past month had standardized mortality ratios of 3.18 and 2.82, respectively; controlling for 10-year age groups (p < 0.001). The standardized mortality ratios for usage 1-29 times/month were 1.8 and 1.48, respectively (p < 0.001). In proportional hazards models that controlled for 30 other risk factors and comorbidities simultaneously, the excess mortality risk associated with usage 30+ times per month remained significant, but hazard ratios were reduced to 1.35 for men and 1.22 for women. CONCLUSIONS: Use of hypnotics was associated with excess mortality. This methodology could not determine if hypnotic compounds caused the risks associated with their use, nor could the risks of individual compounds be determined. Since millions of Americans are currently taking hypnotics, long-term controlled trials are urgently needed to further guide both patients and physicians.

Adult

Breast cancer and Women & Health.

Breast cancer is the most common type of cancer in women. Until recently, most breast cancer research was published in clinical and other specialized medical journals. The recent emergence of effective communication networks and influential advocacy organizations has led to increases in funding for breast cancer research, with the result that research fronts in social as well as medical aspects of breast cancer are rapidly expanding. The five breast cancer articles in this issue of Women & Health cover the broad areas of communications, screening, and policy, highlighting the importance of early detection and treatment and illustrating the dynamics of involvement of women's groups and individual women toward solving problems of education, attitudes, and advocacy.

Breast Neoplasms

Platelet adhesion at high shear rates: the roles of von Willebrand factor/GPIb and the beta 1 integrin alpha 2 beta 1.

We have previously described a monomeric rvWf fragment, Leu504-Lys728 that contains one disulfide bond linking Cys509-Cys695. This fragment, VCL, has previously been shown to inhibit vWf-ristocetin, asialo-vWf, and botrocetin-induced vWf binding and aggregation of platelets. VCL inhibited 50% of vWf binding to heparin, but it did not inhibit vWf binding to type I collagen. At a high shear force (2600-1 sec), VCL inhibited platelet adhesion to the subendothelial surface of human umbilical arteries. The maximum inhibition of platelet adhesion was 83 +/- 4% at a VCL concentration of 7.6 mumol/L. Various monoclonal anti-Very Late Activation antigens (VLA) antibodies were added to the VCL and tested for their ability to enhance the inhibition of platelet adhesion at high shear forces. Of all of the VLA antibodies tested, only the anti-VLA-2 antibody (176D7) inhibited platelet aggregation in the absence of VCL and enhanced the inhibition of platelet adhesion in the presence of VCL. The VLA-2 antibody and VCL together inhibited 96 +/- 4% of platelet adhesion at high shear forces.

Adult

Occupation and the risk of malignant melanoma.

BACKGROUND: The incidence of malignant melanoma is increasing rapidly. The risk for development of malignant melanoma has been reported to be higher in persons of higher socioeconomic status. METHODS: This case-control study explores the relation between occupation and malignant melanoma relative risk through analysis of data collected by the American Cancer Society. A total of 1.2 million people were enrolled in a study of lifestyles and environmental factors in relation to mortality from cancer and other diseases. A total of 2780 persons had a history of malignant melanoma when the study began or developed malignant melanoma during the 6-year study follow-up period. The controls were matched for age, sex, race, and geographic location on an approximately 1:3 basis to persons selected from the remaining people enrolled. RESULTS: In men, malignant melanoma risk was significantly higher in high-paying versus low-paying occupations (odds ratio [OR], = 1.58; P < 0.001) and in white-collar versus blue-collar occupations (OR = 1.33; P < 0.001). No significant conclusions could be drawn for women. No significant difference in risk was noted between those with indoor versus outdoor occupations. Among specific occupational exposures, only exposure to X-rays significantly raised malignant melanoma risk (OR = 1.37; P = 0.002). CONCLUSION: Upper pay scale and white-collar occupations significantly increase the risk for development of malignant melanoma.

Case-Control Studies

Changing trends. An overview of breast cancer incidence and mortality.

The incidence of breast cancer rose about 1% per year between 1940 and 1980 according to data in the Connecticut Tumor Registry. A sharp increase of 32% was reported between 1980 and 1987 in the Surveillance, Epidemiology and End Results Program of the National Cancer Institute. Data from this program shows that the increase in incidence was due to localized cases and cancers of less than 2 cm in greatest dimension. In addition, a sharp increase in carcinoma in situ was observed. The increase in breast cancer incidence coincides with an increased use of mammography in asymptomatic women in the 1980s. Mortality from breast cancer has changed little since the 1930s, but the increases in localized and small-size tumors and decreases in the rate of tumors of 3 cm or larger at diagnosis indicates that breast cancer mortality may start to decrease. Evidence from provisional breast cancer monthly mortality data suggests that there was a 3-6% drop in 1991 compared to 1990.

Adult

Tobacco smoking, alcohol drinking, and cancer of the oral cavity and oropharynx among U.S. veterans.

BACKGROUND: Independent carcinogenic effects of alcohol drinking and tobacco smoking as well as their interaction can be usefully studied in a population of heavy drinkers and smokers. METHODS: A hospital-based case-control study was conducted during 1972 to 1983 in a large Veterans hospital in East Orange, New Jersey. A total of 359 oral cavity-oropharynx cancer cases and 2280 controls were interviewed according to tobacco smoking, use of smokeless tobacco, alcoholic beverage, coffee and tea drinking, race, family origin, religion, and occupation as bartender. RESULTS: Odds ratio of oral cancer increased up to the level of 35 cigarettes per day and 21 whiskey equivalents per day: no further increase was found for higher level of exposure to either factor. A protective effect of quitting smoking was found, but the number of former smokers was small. No difference occurred in oral cancer risk according to type of alcoholic beverage drunk. An interaction effect compatible with a multiplicative model was found between the two exposures. Blacks were at lower risk than whites, and, in the latter group, individuals of Italian origin were at lower risk than individuals from northern or central European countries. CONCLUSIONS: Alcohol drinking and tobacco smoking were responsible for the majority of oral cancer cases in this population of US Veterans.

Adult

Carcinogenic effect of tobacco smoking and alcohol drinking on anatomic sites of the oral cavity and oropharynx.

A series of 359 male patients with 424 cancer lesions of the oral cavity and oropharynx identified at a US Department of Veterans Affairs Medical Center were divided according to site of origin of the lesion and compared with 2,280 controls from the same hospital with respect to exposure to tobacco smoking and alcohol drinking. Sites of origin were: floor of the mouth (153), oral tongue (50), anterior tonsillar pillar (49), soft palate (44), lingual aspect of retromolar trigone (11), alveolar ridge (5), buccal mucosa (4), and hard palate (2). Forty-one patients had cancers in multiple sites. Tobacco smoking was more strongly associated with soft-palate lesions than with lesions in more anterior sites. Patients with cancer of floor of the mouth and oral tongue had higher odds ratios for alcohol drinking than subjects with cancers of other sites. This study supports the hypothesis of the carcinogenic effect of tobacco smoke and alcoholic beverages on the oral mucosa through direct contact.

Adult

Risk factors for fatal colon cancer in a large prospective study.

BACKGROUND: Diet, physical activity, obesity, aspirin use, and family history may all modify the risk of colon cancer, but few epidemiologic studies are large enough to examine these factors simultaneously. PURPOSE: We prospectively assessed the relationship of diet and other factors to risk of fatal colon cancer. METHODS: Using data from Cancer Prevention Study II--an ongoing prospective mortality study--we studied 764,343 adults who, in 1982, completed a questionnaire on diet and other risk factors and did not report cancer or other major illness. We assessed mortality through August 1988 and identified 1150 deaths from colon cancer (611 men and 539 women). Multivariate analyses were used to compare these case patients with 5746 matched control subjects drawn from the cohort. RESULTS: Risk of fatal colon cancer decreased with more frequent consumption of vegetables and high-fiber grains (P for trend = .031 in men and .0012 in women). The relative risk (RR) for the highest versus lowest quintile of vegetable intake was 0.76 in men (95% confidence interval [CI] = 0.57-1.02) and 0.62 in women (95% CI = 0.45-0.86). Dietary consumption of vegetables and grains and regular use of aspirin were the only factors having an independent and statistically significant association with fatal colon cancer. Participants who consumed the least vegetables and grains and no aspirin had a higher risk compared with those who consumed the most vegetables and used aspirin 16 or more times per month. For men in the former category, the RR was 2.4 (95% CI = 1.1-5.3); for women, it was 2.9 (95% CI = 1.3-6.7). Weaker associations were seen for physical inactivity, obesity, total dietary fat, and family history. No associations were seen with consumption of red meat or total or saturated fat in either sex, but this finding must be interpreted cautiously. CONCLUSIONS: These findings support recommendations that increased consumption of vegetables and grains may reduce the risk of fatal colon cancer. Regular use of low doses of aspirin may prove to be an important supplemental measure.

Adult

Level of education and the risk of malignant melanoma.

BACKGROUND: The risk for the development of malignant melanoma has been reported to be higher in persons with more formal education than in individuals with less. OBJECTIVE: To study whether those with more formal education are indeed at more risk for malignant melanoma than those with less formal education. METHODS: This case-control study explores the relation between education and melanoma risk by analyzing data collected by the American Cancer Society. A total of 1.2 million people were surveyed for a history of cancer and followed up for 6 years for the development of any cancer. In total, 2780 white persons had a history of malignant melanoma or developed malignant melanoma during the study period. The controls were age-, sex-, and geographically matched white persons selected from the remaining people enrolled. RESULTS: Both men and women were shown to have a statistically significant increase in the relative risk for malignant melanoma with increasing education level (p less than 0.001 and p = 0.001, respectively). This relation was more striking in men when the relative risk with 95% confidence interval was calculated by sex for each education level. CONCLUSION: Americans with more formal education are at greater risk for malignant melanoma than those with less education.

Educational Status

Cigarette smoking and body weight in the Cancer Prevention Study I.

To investigate the generality of the association of heavy cigarette smoking with increased body weight, the relation of number of cigarettes smoked per day to relative body weight was examined in baseline data for 891,589 participants in a prospective study initiated in 1959. Although the relative weight of cigarette smokers was consistently lower than that of never and exsmokers, men and women smoking two or more packs of cigarettes per day were more likely to be categorized as moderately or severely overweight and less likely to be categorized as underweight than those smoking 10-20 cigarettes per day, despite somewhat greater educational attainment by heavier smokers. These analyses offer support for the temporal generality of the relation between heavier cigarette smoking and greater body weight, and suggest that this phenomenon cannot be explained by historic trends in the socioeconomic stratification of smoking prevalence or smoking dose.

Adult

The changing pattern of lung carcinoma.

In a study of 505 cases of lung carcinoma from a period in which there was a significant change in tobacco-smoking habits, a dramatic shift in the histologic type and location of the lung tumors was observed. Peripheral tumors, found in 30.7% of the carcinomas occurring before 1978, were found in 42% of the carcinomas from 1986 to 1989. The corresponding decrease in the centrally originating bronchial carcinoma was from 69.3% to 57.3%. The greatest change in histologic cancer type was that the incidence of bronchioloalveolar carcinoma more than doubled from 9.3% in the earlier period to 20.3% percent in the 1986-to-1989 period. Corresponding to the decreasing incidence of lung carcinoma, there is a decrease in cancers related to cigarette smoking. A study of cases of lung carcinoma among nonsmokers and former smokers showed a decreased incidence of the bronchogenic cancers and an increase of cancer occurring in the peripheral lung parenchyma. This finding should be validated in other population-based studies, and if confirmed, new studies should be undertaken in an attempt to discover the factors that play a role in the development of such cancers. As an example, viral oncogenes may be a possibility. Viruses were suggested in the past as being related to the development of some of these tumor types.

Adenocarcinoma

A computer model of pancreatic islet glycolysis.

We have modeled an experiment with perifused pancreatic islet cells using our BIOSSIM language. The experiment and the resulting model are concerned with glucose uptake and glycolysis by the beta-cells of pancreatic islets. Although glycolysis appears to be involved in insulin release, we do not have enough information to represent insulin release in detail. The rapid entry of glucose into the beta-cell is promoted by a carrier having a very high tissue capacity. Phosphorylation of glucose by the low affinity enzyme glucokinase appears to be limiting for glycolysis. The effects of several hexose diphosphate activators of phosphofructokinase are modeled. Model behavior is described. The kinetic parameters of the enzyme submodels are given. Because of the difficulties of preparing large amounts of experimental material, information on pancreatic islet metabolism is limited. This model is a plausible explanation of the experimental results. Recent work on the genetically engineered glucose transporter and glucokinase is discussed.

Animals

Association between smoking and leukemia in two American Cancer Society prospective studies.

The association between smoking and leukemia in men and women was analyzed from the data of two prospective studies. Myeloid leukemia was positively associated with smoking in men in both studies (standardized mortality ratios [SMR], 2.44 and 1.32; P less than 0.05), but not with smoking in women. Lymphatic leukemia showed no elevation in risk in men and women in both studies. Animal studies suggest a real biologic difference in leukemogenic effect between the sexes, but further analyses are needed to characterize the smoking effect of leukemia in women.

Adult

Alcohol drinking and mortality among men enrolled in an American Cancer Society prospective study.

We studied whether moderate alcohol drinkers have a lower total and coronary heart disease (CHD) mortality than nondrinkers. Among 276,802 U.S. men aged 40-59 enrolled in 1959 in an American Cancer Society prospective study, 42,756 deaths, 18,771 from CHD, occurred during the following 12 years (3% of the cohort was lost to follow-up). Using nondrinkers (55.3% of the cohort) as a reference category, age- and smoking-stratified relative risks (RR) of total mortality were 0.88 for occasional drinkers, 0.84 for those drinking 1 drink per day, 0.93, 1.02, 1.08, 1.22, and 1.38 for those drinking 2, 3, 4, 5, and 6 or more drinks per day, respectively. RRs of CHD mortality were 0.86, 0.79, 0.80, 0.83, 0.74, 0.85, and 0.92, respectively. Multivariate analysis failed to identify other confounders. No changes in RRs were introduced by excluding subjects with poor health or history of chronic disease at enrollment (32.8% of the cohort) or excluding subjects who died during the first 6 years of follow-up. These data indicate an apparent protective effect of moderate alcohol intake on CHD mortality that cannot be attributed to the inclusion of subjects with CHD or related diseases into the nondrinker category.

Adult