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Biomedical subjects

S H Olson

Publications and source records attributed to S H Olson.

16 recordsLinked to original sources
PubMed2004

Genetic variants in SOD2, MPO, and NQO1, and risk of ovarian cancer.

OBJECTIVE: One way in which parity and use of oral contraceptives may protect against ovarian cancer is by preventing inflammation and oxidative stress associated with ovulation. Since the genes superoxide dismutase (SOD2), myeloperoxidase (MPO), and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress, we investigated whether variants of these genes are associated with risk of ovarian cancer. METHODS: In a hospital-based case-control study, we compared 125 cases and 193 controls with respect to prevalence of (1) the T-->C (val-->ala) substitution at the -9 position in the signal sequence of SOD2; (2) the G-->A substitution at the -463 position in the promoter region of MPO; and (3) the C-->T (pro-->ser) change in exon 6 of NQO1. Genotyping was done using PCR and gel electrophoresis for MPO and NQO1 and using MALDI-TOF mass spectrometry for SOD2. RESULTS: For SOD2, women with the TC (val/ala) or CC (ala/ala) genotypes were at increased risk [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1-4.0]. Results for MPO and NQO1 were in the hypothesized directions but were not statistically significant. For MPO, there was a small inverse association among women with GA or AA genotypes (OR = 0.72, 95% CI 0.43-1.2). For NQO1, the TT (ser/ser) genotype was associated with somewhat increased risk (OR = 2.3, 95% CI 0.69-7.6). CONCLUSIONS: While these results need to be confirmed in other studies, they point to a possible role for genes involved in oxidative stress in the development of ovarian cancer.

Adult↗
PubMed2001

Reported participation in case-control studies: changes over time.

There is concern that participation in case-control studies has declined. To address this question, the author and colleagues reviewed data from 82 US and Canadian case-control studies published in epidemiologic journals during two periods: 1988-1990 and 1997-January 1999. The median year of data collection, which ranged from 1972 to 1996, was the primary independent variable. Reported response among both cases and controls remained constant over this time period. The regression coefficients (beta) were small: For each year, there was a change of 0.15 percentage points for cases (p = 0.56) and -0.16 percentage points for controls (p = 0.54). Possible confounders included the location where the study had been conducted and, for cases, the disease under study (cancer vs. others). After adjustment for these factors in case groups, there was still no association between year of data collection and response: For each year, there was a change of -0.20 percentage points (p = 0.43). After adjustment of results for study location among controls, there was a moderate decline over time: For each year, there was a change of -0.44 percentage points (p = 0.12). Overall, reported response in more recent studies was similar to that in earlier studies; for control groups, this may reflect changes in locations where the studies were conducted.

Bias↗
PubMed2001

Succinic acids as potent inhibitors of plasmid-borne IMP-1 metallo-beta-lactamase.

IMP-1 metallo-beta-lactamase (class B) is a plasmid-borne zinc metalloenzyme that efficiently hydrolyzes beta-lactam antibiotics, including carbapenems, rendering them ineffective. Because IMP-1 has been found in several clinically important carbapenem-resistant pathogens, there is a need for inhibitors of this enzyme that could protect broad spectrum antibiotics such as imipenem from hydrolysis and thus extend their utility. We have identified a series of 2,3-(S,S)-disubstituted succinic acids that are potent inhibitors of IMP-1. Determination of high resolution crystal structures and molecular modeling of succinic acid inhibitor complexes with IMP-1 has allowed an understanding of the potency, stereochemistry, and structure-activity relationships of these inhibitors.

Crystallography, X-Ray↗
PubMed2001

Symptoms of ovarian cancer.

OBJECTIVE: To examine the symptoms of ovarian cancer in patients compared with symptoms experienced by healthy women using a case-control design. METHODS: Cases (n = 168) were women with ovarian cancer diagnosed at two hospitals in New York between 1994 and 1997 who were interviewed shortly after diagnosis. They were compared with healthy women (n = 251 controls) from the community. Women were asked about the prevalence, duration, and constancy of eight symptoms and about use of three types of medications in the 6 to 12 months before diagnosis (cases) or interview (controls). RESULTS: Nearly all the cases (93%) reported at least one symptom, compared with 42% of controls. The most common symptoms among cases were: unusual bloating, fullness, and pressure in the abdomen (71%); unusual abdominal pain or lower back pain (52%); and lack of energy (43%). The proportions of controls reporting these symptoms were 9, 15, and 16%, respectively, resulting in odds ratios and 95% confidence intervals of 25.3 (15.6, 40.9), 6.2 (4.0, 9.6), and 3.9 (2.5, 6.1), respectively, for these symptoms. Bloating, fullness, and pressure was of more recent onset among cases than controls (4.9 months compared with 7.6 months, P =.01). There were only minor differences in reported symptoms between cases with early and later stage disease. CONCLUSION: Unusual bloating, fullness, and pressure, abdominal or back pain, and lack of energy are prominent symptoms in women with ovarian cancer and distinguish them from controls. Information on symptoms may make women and physicians more aware of changes associated with ovarian cancer.

Adult↗
PubMed2001

Dietary antioxidants, supplements, and risk of epithelial ovarian cancer.

Several studies of dietary and serum antioxidant micronutrients (vitamins A, C, and E and beta-carotene) suggest that higher levels may be protective for ovarian cancer. None of these has examined supplements. We used a food frequency questionnaire and additional questions on supplements to study 168 histologically confirmed epithelial ovarian cancer cases, 159 community controls, and 92 hospital-based controls. Antioxidant consumption from diet or supplements was calculated in milligrams or international units per day. In multivariate analyses using only community controls, the highest levels of intake of vitamins C and E from supplements were protective: odds ratio (OR) = 0.40 [95% confidence interval (CI) = 0.21-0.78] and OR = 0.33 (95% CI = 0.18-0.60), respectively. Consumption of antioxidants from diet was unrelated to risk. In analyses combining antioxidant intake from diet and supplements, vitamins C (> 363 mg/day) and E (> 75 mg/day) were associated with reduced risks: OR = 0.45 (95% CI = 0.22-0.91) and OR = 0.44 (95% CI = 0.21-0.94), respectively. Results were similar, with some attenuation toward the null, in analyses combining both control groups. The levels of vitamins C and E associated with the protective effect were well above the current US Recommended Dietary Allowances. These findings support the hypothesis that antioxidant vitamins C and E from supplements are related to a reduced risk of ovarian cancer.

Adult↗
PubMed2000

Selection of control groups by using a commercial database and random digit dialing.

Identifying a control group when cases come from a specialized hospital is a challenge for epidemiologists. The authors compared controls recruited by using a commercial database with those recruited by random digit dialing in the context of a hospital-based case-control study of ovarian cancer. This part of the study was conducted in 1997-1998 among women aged 18 years or older who resided in the New York metropolitan area. A mailing list owner grouped cases into "lifestyle" clusters based on US zip+4 postal code microneighborhoods and generated a random sample of potential controls with the same distribution across the clusters. Controls recruited from the commercial database (n = 82) and from random digit dialing (n = 90) were similar in age and race. Women from the commercial database had somewhat more education and higher incomes and were more similar to the cases on these measures. The control groups resembled each other closely in terms of oral contraceptive use, nulliparity, and religion and differed from the cases on these measures. Response rates were similar for the two groups. Only 28% of the cases were included on the mailing list, indicating that it did not reflect the source population of the cases. Use of a commercial database provided a control group whose socioeconomic factors were similar to those of cases at a lower cost than when random digit dialing was used but did not result in a higher response rate.

Adult↗
PubMed1998

Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of Bacteroides fragilis metallo-beta-lactamase.

BACKGROUND: High level resistance to carbapenem antibiotics in gram negative bacteria such as Bacteroides fragilis is caused, in part, by expression of a wide-spectrum metallo-beta-lactamase that hydrolyzes the drug to an inactive form. Co-administration of metallo-beta-lactamase inhibitors to resistant bacteria is expected to restore the antibacterial activity of carbapenems. RESULTS: Biphenyl tetrazoles (BPTs) are a structural class of potent competitive inhibitors of metallo-beta-lactamase identified through screening and predicted using molecular modeling of the enzyme structure. The X-ray crystal structure of the enzyme bound to the BPT L-159,061 shows that the tetrazole moiety of the inhibitor interacts directly with one of the two zinc atoms in the active site, replacing a metal-bound water molecule. Inhibition of metallo-beta-lactamase by BPTs in vitro correlates well with antibiotic sensitization of resistant B. fragilis. CONCLUSIONS: BPT inhibitors can sensitize a resistant B. fragilis clinical isolate expressing metallo-beta-lactamase to the antibiotics imipenem or penicillin G but not to rifampicin.

Bacteroides fragilis↗
PubMed1998

Relation of time since last birth and parity to survival of young women with breast cancer.

We investigated whether survival was related to recent childbirth or parity in a cohort of 540 women diagnosed with breast cancer before the age of 45 years who were followed for up to 14 years. Women who had given birth within 2 years before their diagnosis of breast cancer were at increased risk of dying, compared with nulliparous women, with an adjusted relative risk of 3.1 (95% confidence interval = 1.8-5.4). There was a moderate association of parity with mortality, with an adjusted relative risk of 1.8 (95% confidence interval = 1.2-2.9) for women with three or more births, compared with nulliparous women.

Adult↗
PubMed1997

Exercise, occupational activity, and risk of endometrial cancer.

We conducted a case-control study in western New York state among 232 women with newly-diagnosed endometrial cancer and 631 controls selected from the community. Physical activity was measured by participation in vigorous exercise and walking at four time periods: at age 16, and at 20, 10, and 2 years before the interview and by occupational activity based on a detailed lifetime history. Women who did a moderate amount of vigorous exercise at age 16 and at 20 years before the interview were at reduced risk as compared with those who reported no activity, with odds ratios (OR) (95% confidence intervals) of 0.51 (0.31-0.83) and 0.50 (0.29-0.89), respectively. However, there was no evidence of declining risk with greater amount of activity. At later times, 10 years and 2 years before the interview, being in the highest group with regard to vigorous activity was associated with a slightly but nor significant lower risk as compared with women who reported no activity; the adjusted OR were 0.72 (0.43-1.19) and 0.67 (0.42-1.09), respectively. Being in the highest category of miles walked at age 16 (i.e., > or = 15 miles per week) was associated with a slightly reduced risk as compared with not walking at all (OR 0.64 (0.26-1.16)), whereas the number of miles walked at other times was not related to reduced risk. Occupational physical activity was not related to the risk of endometrial cancer. Overall, these results indicate that physical activity at levels prevalent in this population has at most a modest relationship to reduced risk of endometrial cancer.

Adolescent↗
PubMed1997

A case-case analysis of factors related to overexpression of p53 in endometrial cancer following breast cancer.

We studied 54 patients diagnosed with endometrial cancer between 1981 and 1994 following a diagnosis of breast cancer. We used a case-case analysis, comparing tumors with and without overexpression of the p53 gene product to evaluate the association of putative p53 mutations with tamoxifen use and other risk factors for endometrial cancer. Twenty-four % of the tumors showed strong positive staining for the p53 gene product. Tumors in a more advanced stage (stage 2, 3, or 4, compared to stage 1) were more likely to overexpress p53 [odds ratio (OR) = 4.2; 95% confidence interval (CI), 1.1-16.2], as were tumors with serous or clear cell, compared to endometrioid, histology (OR = 5.8; 95% CI, 1.3-26.5). There was a small association between p53 overexpression and treatment with tamoxifen for breast cancer (OR = 2.6; 95% CI, 0.69-9.8). There was a strong relationship between overexpression of p53 and having a first-degree relative with breast cancer (OR = 12.3; 95% CI, 2.6-57.4) and between overexpression of p53 and having an additional cancer, i.e., at sites other than breast or endometrium (OR = 7.9; 95% CI, 1.6-40.1). In this group of women, genetic predisposition to cancer, as reflected in family history of breast cancer and personal history of an additional primary cancer, was strongly associated with overexpression of p53 in endometrial tumors. The results suggest that use of tamoxifen may be associated with an increase in tumors that overexpress p53, although the results could be due to chance.

Adult↗
PubMed1995

Body mass index, weight gain, and risk of endometrial cancer.

Excess weight near the time of diagnosis is a well-established risk factor for endometrial cancer; less is known about the influence of weight at earlier periods of a woman's life or weight gain in adulthood. In a case-control study in western New York State, interviews were conducted with 232 incident endometrial cancer cases, diagnosed between 1986 and 1991, and 631 community controls. Body mass index at 16 years of age and 20, 10, and 2 years before interview and changes in body mass index between these time periods were examined. While being relatively heavy at 16 years of age was associated with slightly increased risk [adjusted odds ratio (OR) = 1.28, 95% confidence interval (CI) = 0.84-1.96], large gains over the entire period from 16 years of age to 2 years ago (OR = 3.45, CI = 2.13-5.57) and high body mass index close to the time of diagnosis (OR = 3.21, CI = 2.01-5.15) were associated with greater risk. Differences in mean body mass index between cases and controls increased over time.

Adult↗
PubMed1994

Characteristics of a hypothetical group of hospital controls for a case-control study.

In case-control studies in which cases are ascertained from hospitals, controls are frequently chosen from among patients with other diseases at the same hospitals. This study was undertaken to examine the extent to which a hospital control group is representative of the population to which inferences are made. A hypothetical hospital control group was assembled consisting of 233 men and women aged 40-74 years who were surgical inpatients at the two hospitals in Otsego County, New York, in 1990. The characteristics of this group were compared with the characteristics of 15,563 men and women aged 40-74 years who participated in a privately conducted health census in the same county in 1989 with the use of health-related data collected in the census. In this rural setting, only small differences were found between the hospital control group and the census population on most of the measures considered, including demographic characteristics, certain health behaviors, and the prevalence of common conditions. However, the female hospital controls were more likely to be overweight than the females enumerated in the census, and the men were more likely to have ever smoked cigarettes. These differences were large enough to lead to different interpretations about the strength of the associations between these variables and case-control status.

Adult↗
PubMed1992

Evaluation of random digit dialing as a method of control selection in case-control studies.

Control groups selected by random digit dialing are frequently used in case-control studies. Concern about the potential for bias in these control groups has been expressed, primarily because of low response rates. This study compares the characteristics of a hypothetical control group consisting of 341 men and women aged 40-74 years, selected by random digit dialing and participating in an interview in 1990, with the characteristics of 15,563 men and women aged 40-74 years who participated in a privately conducted census in the same upstate New York county in 1989. For most measures, no differences were seen between the random digit dialing sample and the census population. However, the hypothetical control group was more likely to have had their cholesterol checked in the past 2 years and was somewhat more likely to have had other screening tests as well. In addition, the hypothetical control group was somewhat better educated. The results suggest that, at least in this setting, control groups selected by random digit dialing are representative of the general population in most respects; however, caution should be used when studying the relation between screening tests and disease occurrence by means of case-control studies using controls selected by random digit dialing.

Adult↗
PubMed1983

Responses to questions frequently asked by medical students about family practice.

During their medical school years medical students are frequently exposed to misinformation about family practice from faculty members in other specialties. Responses to 26 questions frequently asked by medical students about family practice are presented with a review of recent literature. These responses may assist medical students and their advisors when considering careers in family practice.

Attitude↗
PubMedDate not supplied

Climate change and health: global to local influences on disease risk.

The World Health Organization has concluded that the climatic changes that have occurred since the mid 1970s could already be causing annually over 150,000 deaths and five million disability-adjusted life-years (DALY), mainly in developing countries. The less developed countries are, ironically, those least responsible for causing global warming. Many health outcomes and diseases are sensitive to climate, including: heat-related mortality or morbidity; air pollution-related illnesses; infectious diseases, particularly those transmitted, indirectly, via water or by insect or rodent vectors; and refugee health issues linked to forced population migration. Yet, changing landscapes can significantly affect local weather more acutely than long-term climate change. Land-cover change can influence micro-climatic conditions, including temperature, evapo-transpiration and surface run-off, that are key determinants in the emergence of many infectious diseases. To improve risk assessment and risk management of these synergistic processes (climate and land-use change), more collaborative efforts in research, training and policy-decision support, across the fields of health, environment, sociology and economics, are required.

Communicable Diseases↗