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L Steele

Publications and source records attributed to L Steele.

At least 19 recordsLinked to original sources
PubMed1998

Response to radiation therapy and prognosis in breast cancer patients with BRCA1 and BRCA2 mutations.

BACKGROUND AND PURPOSE: The purpose of this study is to evaluate overall survival in BRCA1 or BRCA2 breast cancer patients, describe presenting stage, review histologic findings and evaluate response to radiotherapy. MATERIALS AND METHODS: A retrospective study was performed evaluating breast cancer patients with known mutations of BRCA1 or BRCA2. Patients from 12 different pedigrees were cross-referenced with the Utah Cancer Registry (UCR), histologic findings were verified and radiotherapy records were reviewed for acute response to treatment. Actuarial survival calculations were performed and patients were matched for age, date of diagnosis and tumor size. RESULTS: Thirty breast cancer patients with BRCA1 mutations were found to have 34 breast cancers (four had bilateral metachronous lesions) and 20 breast cancer patients with BRCA2 mutations were found to have 22 breast cancers (two had bilateral metachronous disease). The median age at diagnosis was 49 years (range 21-77 years) and 42 years (range 23-83 years), respectively, for BRCA1 and BRCA2 patients. Unusual histologic types of breast cancers were represented with 7% (4/56) medullary and 5% (3/56) lobular carcinomas. Complete staging was possible for 63% (35/56) of cancers. Stages I, II, III and IV represented 26, 63, 6 and 6% of cancers, respectively. The most severe radiation reaction was moist desquamation which was self-limiting and developed in 29% (6/21) of irradiated patients. The mean follow-up was 9.8 and 7.5 years for BRCA1 and BRCA2 cancers, respectively. Kaplan-Meier survival analysis demonstrated 5-year survival values of 75% for BRCA1 patients, 73% for BRCA2 patients, 70% for matched controls and 69% for UCR controls. No statistically significant differences were evident between the groups at 5 or 10 years. CONCLUSIONS: Despite their younger age at presentation, breast cancer patients harboring BRCAI or BRCA2 mutations present at a similar stage, display a normal acute reaction to radiotherapy and have a similar prognosis when compared with sporadic breast cancer patients.

Adult↗
PubMed1998

Emerging infectious diseases: can we meet the challenge?

Demonstration of quality health care includes documentation of outcomes of care. Surveillance is a comprehensive method of measuring outcomes and related processes of care, analyzing the data, and providing information to members of the health care team to assist in improving those outcomes. Surveillance is an essential component of effective clinical programs designed to reduce the frequency of adverse events such as infection or injury.

Communicable Disease Control↗
PubMed1998

Recommended practices for surveillance. Association for Professionals in Infection Control and Epidemiology, Inc. Surveillance Initiative working Group.

Demonstration of quality health care includes documentation of outcomes of care. Surveillance is a comprehensive method of measuring outcomes and related processes of care, analyzing the data, and providing information to members of the health care team to assist in improving those outcomes. Surveillance is an essential component of effective clinical programs designed to reduce the frequency of adverse events such as infection or injury. Although there is no single or "right" method of surveillance design or implementation, sound epidemiologic principles must form the foundation of effective systems and must be understood by key participants in the surveillance program and supported by senior management. Teamwork and collaboration across the health care spectrum are important for the development of surveillance plans. Each health care organization must tailor its surveillance systems to maximize resources by focusing on population characteristics, outcome priorities, and organizational objectives. To ensure quality of surveillance, the following elements must be incorporated: A written plan should serve as the foundation of any surveillance program. The plan should outline important objectives and elements of the surveillance process so that resources can be targeted appropriately. Thoroughness or intensity of surveillance for an area of interest must be maintained at the same level over time. Fluctuations of a surveillance rate have no meaning unless the same level of data collection is maintained. External rate comparisons are meaningless unless the systems used have comparable intensity. All the elements of surveillance should be used with consistency over time. This includes application of surveillance definitions and rate calculation methods. Personnel resources need to be appropriate for the type of surveillance being performed. This includes trained professionals who understand epidemiology and who have access to continuing professional education opportunities. Other resources essential to surveillance include computer support, information and technology services, clerical services, and administrative understanding and support to maintain a quality program. As a means of quality control and to ensure accuracy, the data and process of surveillance should undergo periodic evaluation and validation. This document is intended to assist professionals who plan and conduct surveillance programs as well as those who assure that there is appropriate organizational support to accomplish appropriate surveillance. While design of surveillance systems must be unique for each organization, incorporation of these seven core Recommended Practices for Surveillance provides a scientific framework to approach surveillance programs.

Cross Infection↗
PubMed1997

BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing.

CONTEXT: A mutation in the BRCA1 gene may confer substantial risk for breast and/or ovarian cancer. However, knowledge regarding all possible mutations and the relationship between risk factors and mutations is incomplete. OBJECTIVES: To identify BRCA1 mutations and to determine factors that best predict presence of a deleterious BRCA1 mutation in patients with breast and/or ovarian cancer. DESIGN: A complete sequence analysis of the BRCA1 coding sequence and flanking intronic regions was performed in 798 women in a collaborative effort involving institutions from the United States, Italy, Germany, Finland, and Switzerland. PARTICIPANTS: Institutions selected 798 persons representing families (1 person for each family) thought to be at elevated a priori risk of BRCA1 mutation due to potential risk factors, such as multiple cases of breast cancer, early age of breast cancer diagnosis, and cases of ovarian cancer. No participant was from a family in which genetic markers showed linkage to the BRCA1 locus. MAJOR OUTCOME MEASURES: Sequence variants detected in this sample are presented along with analyses designed to determine predictive characteristics of those testing positive for BRCA1 mutations. RESULTS: In 102 women (12.8%), clearly deleterious mutations were detected. Fifty new genetic alterations were found including 24 deleterious mutations, 24 variants of unknown significance, and 2 rare polymorphisms. In a subset of 71 Ashkenazi Jewish women, only 2 distinct deleterious mutations were found: 185delAG in 17 cases and 5382insC in 7 cases. A bias in prior reports for mutations in exon 11 was revealed. Characteristics of a patient's specific diagnosis (unilateral or bilateral breast cancer, with or without ovarian cancer), early age at diagnosis, Ashkenazi Jewish ethnicity, and family history of cancer were positively associated with the probability of her carrying a deleterious BRCA1 mutation. CONCLUSIONS: Using logistic regression analysis, we provide a method for evaluating the probability of a woman's carrying a deleterious BRCA1 mutation for a wide range of cases, which can be an important tool for clinicians as they incorporate genetic susceptibility testing into their medical practice.

Breast Neoplasms↗
PubMed1997

Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13.

The penetrance of the BRCA2 gene on chromosome 13q12-13 has been estimated in two large, systematically ascertained, linked families, by use of a maximum-likelihood method to incorporate both cancer-incidence data and 13q marker typings in the families. The cumulative risk of breast cancer in female gene carriers was estimated to be 59.8% by age 50 years (95% confidence interval [95% CI] 25.9%-78.5%) and 79.5% by age 70 years (95% CI 28.9%-97.5%). The cumulative risk of breast cancer in male carriers was estimated to be 6.3% (95% CI 1.4%-25.6%) by age 70 years. There was no evidence of any risk difference between the two families. These results indicate that the lifetime breast cancer risk in BRCA2 carriers, for at least a subset of mutations, is comparable to that for BRCA1. A significant excess of ovarian cancer in gene carriers was observed (relative risk 17.69, based on three cases), but the absolute risk of ovarian cancer was less than that reported for BRCA1. Significant excesses of laryngeal cancer (relative risk 7.67, based on two possible carriers) and prostate cancer (relative risk 2.89, based on five possible carriers) were also observed. One case of ocular melanoma, as well as a second eye cancer of unspecified histology, occurred in obligate gene carriers.

BRCA2 Protein↗
PubMed1997

Immune responses associated with chronic fatigue syndrome: a case-control study.

An exploratory case-control study was conducted to assess whether the many reported differences in the immune function of chronic fatigue syndrome (CFS) patients are detectable in rigorously defined cases of CFS. Although many studies have reported differences between cases and controls in various measures of immune function, none of these differences were found in all studies. In this study, no differences were found in white blood cell numbers; immune complex, complement, or serum immunoglobulin levels; delayed type hypersensitivity and allergic responses; NK cell function; and proliferative responses to mitogens and antigens. Marginal differences were detected in cytokine responses and in cell surface markers in the total CFS population. However, when the patients were subgrouped by type of disease onset (gradual or sudden) or by how well they were feeling on the day of testing, more pronounced differences were seen.

Adolescent↗
PubMed1997

Quantitative methods in research on complementary and alternative medicine. A methodological manifesto. NIH Office of Alternative Medicine.

OBJECTIVES: This article summarizes the deliberations of the Quantitative Methods Working Group convened by the National Institutes of Health (NIH) in support of the NIH Office of Alternative Medicine. METHODS: The working group was charged with identifying methods of study design and data analysis that can be applied to empirical research on complementary and alternative medicine. This charge was broad and inclusive and addressed the evaluation of alternative therapies, the investigation of the basic science of complementary medical systems, studies of health promotion and disease prevention, and health services research. RESULTS: The working group produced a "methodological manifesto," a summary list of seven recommended methodological guidelines for research on alternative medicine. These recommendations emphasize the robustness of existing research methods and analytic procedures despite the substantive unconventionality of alternative medicine. CONCLUSIONS: Contrary to the assertions of many researchers and alternative practitioners, established methodologies (eg, experimental trials, observational epidemiology, social survey research) and data-analytic procedures (eg, analysis of variance, logistic regression, multivariate modeling techniques) are quite satisfactory for addressing the majority of study questions related to alternative medicine, from clinical research on therapeutic efficacy to basic science research on mechanisms of pathogenesis and recovery.

Clinical Trials as Topic↗
PubMed1996

Paying for PREP.

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Education, Nursing, Continuing↗
PubMed1996

Wish you were here?

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Education, Nursing, Baccalaureate↗
PubMed1996

Stress busters.

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Burnout, Professional↗
PubMed1996

Sphingomyelin-derived lipids differentially regulate the extracellular signal-regulated kinase 2 (ERK-2) and c-Jun N-terminal kinase (JNK) signal cascades in airway smooth muscle.

In ASM cells platelet-derived growth factor stimulates rapid transient sphingosine phosphate formation, the activation of extracellular signal-regulated kinase 2 (ERK-2), the phosphorylation of p70(56K), and a ninefold increase in DNA synthesis. In contrast, this growth factor fails to activate c-Jun N-terminal kinase (JNK). Based upon these findings, we have tested whether the sphingomyelin-derived sphingolipids play a role in growth factor signalling by assessing their effect on ERK-2, JNK, and p70(56K). We demonstrate that sphingosine phosphate induces the activation of ERK-2, is ineffective against JNK, and fails to induce the phosphorylation of p70(56K). The latter may explain why it is a poor mitogen when added directly to ASM cells. In contrast, sphingosine and cell-permeable ceramides elicit the prominent tyrosyl phosphorylation and activation of JNK, are poor stimulators of ERK-2, and do not induce the phosphorylation of p70(56K). Therefore, the specificity of signalling through either ERK-2 or JNK cascades may be determined by the rapid agonist-dependent interconversion of these sphingomyelin-derived lipids. This may also provide a dynamic mechanism that enables growth factors and cytokines to elicit pleiotropic cell responses, such as proliferation and cell survival. For instance, both ceramide and sphingosine will elicit growth arrest via activation of JNK, whereas sphingosine phosphate will potentiate growth-factor-stimulated DNA synthesis, a consequence of the activation of ERK-2, Furthermore, under certain conditions, sphingosine and ceramide stimulate cAMP formation, a negative modulator of cell growth, whereas sphingosine phosphate depresses cAMP, thereby enhancing its own growth-promoting properties. From these studies, it is evident that sphingosine phosphate displays a signalling profile that is consistent with it mediating part of the action of platelet-derived growth factor.

Animals↗