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Biomedical subjects

L Bernstein

Publications and source records attributed to L Bernstein.

At least 37 records · Page 2Linked to original sources
PubMed2000

Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies.

We evaluated whether our previous reports of increased postmenopausal breast cancer risk with higher body mass index (BMI) or of reduced premenopausal and postmenopausal breast cancer risk with higher physical activity levels varied according to the tumor's estrogen receptor (ER) and progesterone receptor (PR) status. Participants enrolled in either of two population-based case-control studies in Los Angeles County, California: one of premenopausal women (ages < or = 40 years), and one of postmenopausal women (ages 55-64 years). Case participants were diagnosed for the first time with in situ or invasive breast cancer from 7/1/83 through 12/31/88 (premenopausal women) or from 3/1/87 through 12/31/89 (postmenopausal women). Joint ER/PR status was collected for 424 premenopausal and 760 postmenopausal case participants. The analysis included 714 premenopausal and 1091 postmenopausal age-matched, race-matched (white or Hispanic), parity-matched (premenopausal women only), and residential neighborhood-matched control participants. Among the postmenopausal women, obesity was associated with an increased odds of ER+/PR+ breast cancer (odds ratio, 2.45 for women in the highest versus the lowest body mass index quartile; 95% confidence interval, 1.73-3.47). Body mass index was associated with neither ER-/PR- tumors among the postmenopausal women nor with any ER/PR subgroup among the premenopausal women. For both premenopausal and postmenopausal women, higher recreational physical activity levels (> or = 17.6 MET-hours/week versus no activity) were associated with a 30-60% reduction in risk of nearly all ER/PR subtypes, although the associations were generally of borderline statistical significance. Examining these potentially modifiable breast cancer risk factors by tumor ER and PR status may provide us with greater insight into breast cancer etiology and the mechanisms underlying the risk factor associations.

Adult↗
PubMed1999

Tamoxifen therapy for breast cancer and endometrial cancer risk.

BACKGROUND: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. METHODS: We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. RESULTS: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1. 07-2.17). Risk increased with duration of tamoxifen use (P for trend =.0002). Women with more than 5 years of exposure to tamoxifen had 4. 06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P =.10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. CONCLUSIONS: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.

Aged↗
PubMed1999

Lack of association between hepatitis C infection and development of AIDS-related lymphoma.

Hepatitis C virus (HCV) has been associated with various lymphoproliferative disorders, and a high prevalence (9%-32%) of chronic HCV infection has been demonstrated among patients with lymphoma. Dual coinfection by HIV and HCV has been demonstrated in approximately 40% of certain populations of HIV-infected individuals. Because of this high prevalence of coinfection by HIV and HCV, the known relations between HCV and lymphoproliferative disorders, and the association of HIV and B cell lymphoma, the potential association between chronic HCV and the development of AIDS-related lymphoma was examined. The prevalence of HCV infection in HIV-infected patients with lymphoma was compared with that in patients with AIDS, diagnosed on the basis of an illness other than lymphoma. Risk factors for HCV infection, overall, were also evaluated. Evidence of HCV infection was ascertained by assessing anti-HCV antibodies, and HCV RNA in serum. The study consisted of 99 homosexual/bisexual men with AIDS-related lymphoma, and 43 other AIDS patients. HCV infection was detected in 11 of 99 (11.1 %) men with lymphoma, and in 5 of 43 (11.6%) other AIDS patients. Further, in patients with AIDS-related lymphoma, no relation was found between HCV infection and lymphoma histology or site. History of use of injected illicit drugs was associated with a significantly elevated risk of HCV infection in the combined group of lymphoma and other AIDS patients. The current study demonstrates no relation between dual infection by HIV and HCV and subsequent increased risk of lymphoma.

AIDS-Related Opportunistic Infections↗
PubMed1999

The Goldman algorithm revisited: prospective evaluation of a computer-derived algorithm versus unaided physician judgment in suspected acute myocardial infarction.

BACKGROUND: It has been nearly a decade since Goldman's computer-driven algorithm to predict myocardial infarction was validated. Despite the potential to avoid admission of patients without acute myocardial infarction (AMI) to the coronary care unit (CCU), the routine use of computer-generated protocols has not been widely adopted. METHODS: Two hundred consecutive patients admitted to a university-affiliated community hospital with the suspected diagnosis of AMI as determined by physicians without the aid of the Goldman protocol underwent a blinded prospective evaluation to assess the performance of the Goldman algorithm in predicting the presence of AMI. Over the same time period, the Goldman algorithm was applied by retrospective chart review in 762 patients with non-AMI admitting diagnoses. Prospective history, physical examination, and electrocardiographic data were obtained within 24 hours of admission to the CCU by a physician blinded to each patient's clinical course. Retrospective chart reviews were conducted for 762 patients with chest pain given with non-AMI diagnoses. RESULTS: The diagnosis of AMI was confirmed in 68.5% (137/200) of patients with suspected AMI admitted to the CCU. In prospective parallel evaluations the Goldman algorithm predicted the presence of AMI in 167 (83.5%) of these 200 patients. All 137 confirmed patients with AMI were correctly identified by the Goldman algorithm. All major in-hospital complications occurred in the 137 patients who were diagnosed as having AMI. Of the 762 patients with chest pain with non-AMI diagnoses, only 27 (3.5%) sustained an AMI. The Goldman algorithm predicted the presence of AMI in 85% (23/27) of these patients. Adherence to the use of Goldman's algorithm in the triage of chest pain could have prevented 16.5% of CCU admissions for AMI. CONCLUSIONS: Routine adherence to the Goldman algorithm for the evaluation of patients with acute chest pain could have decreased the number of CCU admissions for suspected AMI by 16. 5%. Because major in-hospital complications occurred only in patients with AMI, this strategy would result in significant cost savings to our health care system without jeopardizing patient safety.

Algorithms↗
PubMed1999

The stressful condition as a nutritionally dependent adaptive dichotomy.

The injured body manifests a cascade of cytokine-induced metabolic events aimed at developing defense mechanisms and tissue repair. Rising concentrations of counterregulatory hormones work in concert with cytokines to generate overall insulin and insulin-like growth factor 1 (IGF-1), postreceptor resistance and energy requirements grounded on lipid dependency. Salient features are self-sustained hypercortisolemia persisting as long as cytokines are oversecreted and down-regulation of the hypothalamo-pituitary-thyroid axis stabilized at low basal levels. Inhibition of thyroxine 5'-deiodinating activity (5'-DA) accounts for the depressed T3 values associated with the sparing of both N and energy-consuming processes. Both the liver and damaged territories adapt to stressful signals along up-regulated pathways disconnected from the central and peripheral control systems. Cytokines stimulate liver 5'-DA and suppress the synthesis of transthyretin (TTR), causing the drop of retinol-binding protein (RBP) and the leakage of increased amounts of T4 and retinol in free form. TTR and RBP thus work as prohormonal reservoirs of precursor molecules which need to be converted into bioactive derivatives (T3 and retinoic acids) to reach transcriptional efficiency. The converting steps (5'-DA and cellular retinol-binding protein-I) are activated by T4 and retinol, themselves operating as limiting factors of positive feedback loops. Healthy adults with normal macrophage functioning and liver parenchymal integrity, who submitted to a stress of medium severity, are characterized by TTR-RBP plasma levels reduced by half and an estimated ten-fold increase in free ligand disposal to target cells during the days ensuing injury. This transient hyperthyroid and hyperretinoid climate creates a second defense line strengthening and fine-tuning the effects primarily initiated by cytokines. The suicidal behavior of thyroxine-binding globulin (TBG), corticosteroid-binding globulin (CBG), and IGFBP-3 allows the occurrence of peak endocrine and mitogenic influences at the site of inflammation. The production rate of TTR by the liver is the main determinant of both the hepatic release and blood transport of holoRBP, which explains why poor nutritional status concomitantly impairs thyroid- and retinoid-dependent acute-phase responses, hindering the stressed body to appropriately face the survival crisis. The prognostic significance of low TT4 blood levels may be assigned to the exhaustion of extrathyroidal hormonal pools normally stored in liver and plasma but markedly shrunken in protein-depleted states. These data offer new insights into the mechanisms whereby preexisting malnutrition and stressful complications are interrelated, emphasizing the pivotal role played by TTR in that context.

Adaptation, Physiological↗
PubMed1999

The five-year evolution of a malnutrition treatment program in a community hospital.

BACKGROUND: Studies suggest that 30%-55% of hospitalized patients are at risk for malnutrition, an avoidable comorbidity contributing to increases in hospitalization and readmission, length of stay, complications, and mortality. Yet a variety of issues have impeded many hospitals' implementation of effective nutrition intervention programs. BENCHMARKING STUDY: St Francis Hospital (SFH), a 395-bed community acute care facility in Wilmington, Delaware, participated in a nationwide benchmark study in fall 1993. In comparison with the 12-hospital means, data for SFH showed both delays in initiating a nutrition care plan for acutely ill patients and a significantly higher risk for malnutrition. NUTRITION SCREENING PILOT: A pilot study was implemented in 1994 to identify nutrition needs within 48 hours of admission as a first step in the improvement process. Although interventions occurred earlier for a greater number of high-risk patients, nutrition intervention was not being provided in a uniform and timely manner. THE MALNUTRITION CLINICAL PATHWAY: A free-standing hospital committee, the Nutrition Care Committee (NCC), with guidance from the care management department, began developing a malnutrition pathway that would serve as an integrated plan for providing nutrition care to high-risk patients. The original pathway was organized into four stages that outlined the progression and timing of care--identification of the patient at high risk for malnutrition, nutrition care decisions, treatment in progress (the remainder of the patient's hospitalization), and discharge planning. OUTCOME STUDIES: Outcome studies were conducted in 1996 and again in 1998 to assess the malnutrition treatment pathway's impact on patient health outcomes and the cost of care. The 1996 outcome study indicated significant improvements in the identification of high-risk patients (from 25.9% to 86%) and the timeliness of nutrition intervention (from 6.9 days to 2.4 days). A second outcome study was conducted in 1998, following revision of the pathway. Comparison of the 1996 after-pathway patient population with a matched study group in 1998 indicated reductions in average length of stay from 10.8 to 8.1 days; the incidence of major complications from 75.3% to 17.5%; and 30-day readmission rates from 16.5% to 7.1%. DISCUSSION: The performance improvement project described in this article began with SHF's voluntary participation in an interdisciplinary benchmarking study and continued when it was apparent that SFH had an opportunity for performance improvement. Forming an NCC at SFH was the first step in a process that gained the administrative support necessary to fully develop the program. SUMMARY AND CONCLUSIONS: SFH has developed and implemented a malnutrition treatment program that is integrated into the care plan of all acute care patients and is included in the discharge planning process. Outcome studies have demonstrated the effect of the malnutrition treatment program on patient recovery and cost of care.

Algorithms↗
PubMed1999

Alcohol consumption and breast cancer oestrogen and progesterone receptor status.

We examined the role of alcohol on the risk of breast cancer by the joint oestrogen receptor (ER) and progesterone receptor (PR) status of the tumour using data from two case-control studies conducted in Los Angeles County, USA. Eligible premenopausal patients were 733 women aged < or =40 years and first diagnosed from 1 July 1983 to 1 January 1989. Eligible postmenopausal patients were 1169 women aged 55-64 years and first diagnosed from 1 March 1987 to 31 December 89. Patients were identified by the University of Southern California Cancer Surveillance Program. Neighbourhood controls were individually matched to patients by parity (premenopausal patients) and birth date (+/-3 years). ER and PR status were obtained from medical records for 424 premenopausal and 760 postmenopausal patients. The analyses included 714 premenopausal and 1091 postmenopausal control subjects. Alcohol use was generally not associated with premenopausal risk of breast cancer, regardless of hormone-receptor status. Among the postmenopausal women, those who consumed, on average, > or =27 g of alcohol/d experienced an odds ratio (OR) of 1.76 [95% confidence interval (CI) 1.14-2.71] for ER-positive/PR-positive breast cancer relative to women who reported no alcohol consumption. Alcohol use was less clearly associated with risk of other receptor types among postmenopausal women. These data suggest that alcohol may preferentially increase risk of ER-positive/PR-positive breast cancer in postmenopausal women.

Adult↗
PubMed1999

Diet, body size and menarche in a multiethnic cohort.

A multiethnic cohort of 1378 Southern California school girls aged 8-13 years was followed for 4 years to evaluate factors predicting age at menarche, a risk factor for breast cancer. Height and weight were measured and dietary intake was assessed using a semi-quantitative food frequency questionnaire. Of 939 girls providing data on menarcheal status, 767 were premenarcheal at the start of the study; 679 girls provided acceptable dietary data and were included in the analyses. Cox proportional hazards models were used to assess the relationship between diet, body size, ethnicity and age at menarche. Hispanic, Asian/Pacific Island and African-American girls were more likely to experience early menarche than non-Hispanic white girls. Tall (> 148.6 cm) versus short (< 135.9 cm) girls experienced earlier menarche (relative hazard (RH) = 2.9, 95% confidence interval (CI) 2.1-4.1) as did those with high Quetelet's index (QI, kg m(-2)) (> 20.7) versus low QI (< 16.1) (RH = 2.2, 95% CI 1.7-2.9). Of all the dietary variables analysed, only energy intake was related to age at menarche. High versus low energy intake (> 12,013 kJ vs < 7004 kJ) was associated with a delay in menarche (RH = 0.7, 95% CI 0.5-0.9); this finding was limited to a subset of heavy Hispanic girls who appeared to underreport their dietary intake.

Adolescent↗
PubMed1999

Lifetime exercise activity and breast cancer risk among post-menopausal women.

Lifetime exercise activity has been linked to breast cancer risk among young women. However, no study has specifically evaluated whether lifetime exercise activity is related to the breast cancer risk of post-menopausal women. We conducted a population-based case-control study of post-menopausal white women (1123 newly diagnosed cases and 904 healthy controls) aged 55-64 who lived in Los Angeles County, California, USA to evaluate this relationship. Although neither exercise activity from menarche to age 40 years, nor exercise after age 40 separately predicted breast cancer risk, risk was lower among women who had exercised each week for at least 17.6 MET-hours (metabolic equivalent of energy expenditure multiplied by hours of activity) since menarche than among inactive women (odds ratio (OR) = 0.55; 95% confidence interval (CI) 0.37-0.83). Exercise activity was not protective for women who gained considerable (> 17%) weight during adulthood. However, among women with more stable weight, breast cancer risk was substantially reduced for those who consistently exercised at high levels throughout their lifetime (OR = 0.42; 95% CI 0.24-0.75), those who exercised more than 4 h per week for at least 12 years (OR = 0.59; 95% CI 0.40-0.88), and those who exercised vigorously (24.5 MET-hours per week) during the most recent 10 years (OR = 0.52; 95% CI 0.32-0.85). Strenuous exercise appears to reduce breast cancer risk among post-menopausal women who do not gain sizable amounts of weight during adulthood.

Adult↗
PubMed1999

The risk of angiosarcoma following primary breast cancer.

Lymphangiosarcoma of the upper extremity is a rare and aggressive tumour reported to occur following post-mastectomy lymphoedema (Stewart-Treves syndrome). Haemangiosarcoma, a related rare tumour, has occasionally been reported to occur in the breast following irradiation. We conducted a case-control study using the University of Southern California-Cancer Surveillance Program, the population-based cancer registry for Los Angeles County, to evaluate the relationship between invasive female breast cancer and subsequent upper extremity or chest lymphangiosarcoma and haemangiosarcoma together referred to as angiosarcoma. Cases were females diagnosed between 1972 and 1995 with angiosarcoma of the upper extremity (n = 20) or chest (n = 48) who were 25 years of age or older and residing in Los Angeles County when diagnosed. Other sarcomas at the same anatomic sites were also studied. Controls were females diagnosed with cancers other than sarcoma during the same time period (n = 266,444). Cases and controls were then compared with respect to history of a prior invasive epithelial breast cancer. A history of breast cancer increased the risk of upper extremity angiosarcoma by more than 59-fold (odds ratio [OR] = 59.3, 95% confidence interval [95% CI] = 21.9-152.8). A strong increase in risk after breast cancer was also observed for angiosarcoma of the chest and breast (OR = 11.6, 95% CI = 4.3-26.1) and for other sarcomas of the chest and breast (OR = 3.3, 95% CI = 1.1-1.7).

Adult↗
PubMed1999

p53 mutations and expression in ovarian cancers: correlation with overall survival.

The p53 gene is altered in approximately 50% of all human malignancies. p53 overexpression, identified by immunohistochemistry, and p53 mutations, identified by single-strand conformational polymorphism (SSCP) and DNA sequencing, have been described in ovarian cancers. p53 overexpression has been correlated with poor outcome for women with ovarian cancer in some studies. With only limited data, the assumption has been made that p53 overexpression corresponds to p53 mutations. The purpose of this investigation was to assess p53 alterations in ovarian cancer to determine if p53 overexpression corresponds with mutations in the p53 gene, and to assess whether either predicts clinical outcome in ovarian carcinoma. Frozen ovarian carcinoma tumor specimens from 105 patients were analyzed by immunohistochemical staining for p53 expression. SSCP was used to screen for mutations and DNA sequencing was used to confirm the specific mutation in exons 2 to 11, encompassing the entire p53 open reading frame. Those ovarian carcinomas identified as wild-type p53 by SSCP were subjected to automated DNA sequence analysis of the entire open reading frame. Relative to DNA sequence analysis, the sensitivity of SSCP was 85% and the specificity was 98%. Immunohistochemical staining demonstrated that 72 of the 105 (69%) cases had positive immunostaining. SSCP and DNA sequencing identified and confirmed mutations in 60 of the 105 carcinomas (57%). Although there was a statistically significant association between p53 immunostaining and p53 mutations (p = 0.0002), false-negative and -positive results were identified. Tumor grade (p = 0.03), stage (p = 0.08), and overall survival (p = 0.15) were moderately associated with positive p53 immunostaining. Patients with p53 mutations and overexpression had shorter overall patient survival (p = 0.02). The findings demonstrated that, individually, p53 mutations and p53 overexpression were each related to shorter patient survival, but the strongest predictor of outcome was a combination of both mutations and overexpression. Comparisons of overall survival for women with mutations in loop 2, loop 3, and the loop-sheet-helix domains together showed a statistically significant difference in survival compared to survival of women whose ovarian cancers had other mutations (p = 0.046).

Adult↗
PubMed1999

Reproductive and hormonal risk factors for thyroid cancer in Los Angeles County females.

We conducted an individually matched case-control study (292 pairs) of female thyroid cancer patients to examine the role of reproductive history and exogenous hormones in this disease. Radiation treatment to the head or neck [28 cases and 2 controls exposed; odds ratio (OR), 14.0; 95% confidence interval (CI), 3.5-121.3] and certain benign thyroid diseases (including adolescent thyroid enlargement, goiter, and nodules or tumors) were strongly associated with thyroid cancer. Irregular menstruation increased risk (OR, 1.8; 95% CI, 0.9-3.7). Age at menarche and pregnancy history were not related to disease. Women with natural menopause and hysterectomized women without oophorectomy had no increase in risk, but disease risk was elevated in women with bilateral oophorectomy (OR, 6.5; 95% CI, 1.1-38.1). In general, use of oral contraceptives and other exogenous estrogens was not associated with thyroid cancer. However, risk increased with number of pregnancies in women using lactation suppressants (P = 0.03) and decreased with duration of breastfeeding (P = 0.04). These data provide only limited support for the hypothesis that reproductive and hormonal exposures are responsible for the marked excess of thyroid cancer risk in adult females.

Adenocarcinoma, Follicular↗
PubMed1998

Randomised controlled trial of prophylactic antibiotics before insertion of intrauterine devices. IUD Study Group.

BACKGROUND: The value of antibiotic prophylaxis before insertion of an intrauterine device (IUD) remains uncertain. We undertook a triple-masked, randomised, placebo-controlled trial to find out whether such prophylaxis reduces the rate of IUD removal within 90 days. METHODS: 11 clinic sites in southern California enrolled women who requested IUD insertion and were at low risk of sexually transmitted infection according to self-reported medical history. We randomly assigned 1985 participants either 500 mg azithromycin or placebo capsules of identical appearance taken about 1 h before insertion of a Copper T 380A IUD. 118 women did not have an IUD inserted. We followed up 1833 of the remaining 1867 (98%) participants for at least 90 days after insertion. FINDINGS: The rate of IUD removal for any reason other than partial expulsion was 3.8% (35/918) in the antibiotic group and 3.4% (31/915) in the placebo group (relative risk 1.1 [95% CI 0.7-1.8]). The two treatment groups sought medical attention with equal frequency (mean 38 visits per 100 women). During the 90 days after IUD insertion, only one woman from each assignment group had salpingitis, as defined by established criteria. INTERPRETATION: Prophylaxis with azithromycin did not affect the likelihood that a woman would retain her IUD at 90 days or the frequency of postinsertion medical attention. In appropriately screened women, the risk of upper-genital-tract infection is negligible after IUD insertion, with or without the administration of prophylactic antibiotics.

Adult↗
PubMed1998

Delayed appearance of distal coronary perforation following stent implantation.

Coronary perforations are usually apparent immediately after the occurrence. We report a case of a 67-year-old woman where coronary perforation presented 16 hours after the procedure. This case illustrates the need for extra vigilance and careful evaluation of distal vasculature while using stiff coronary guidewires.

Aged↗