Biomedical subjects

R J Winn

Publications and source records attributed to R J Winn.

At least 19 recordsLinked to original sources

PubMed1999

Clinical practice guidelines in the management of gynecologic malignancies.

The need for guidelines in managing gynecologic cancer is addressed in the first part of this article. Second, the guideline development process that enables the practitioner to judge the validity and usefulness of proffered guidelines is detailed. An important element in this discussion is an exploration of the shortcomings, either real or perceived, of the process. The last section focuses on issues relating to the implementation of guidelines and some of the obstacles that one may encounter as the programs evolve.

Female↗

PubMed1998

Benzo[a]pyrene diol epoxide and bleomycin sensitivity and susceptibility to cancer of upper aerodigestive tract.

BACKGROUND: Tobacco smoking is an established risk factor for cancers of the upper aerodigestive tract, and measurement of chromosomal aberrations, i.e., chromatid breaks, induced in lymphocytes in vitro by bleomycin has been shown to be a predictor of risk for these cancers. In a case-control study, we recruited case subjects who were previously treated with surgery and/or radiotherapy for stage I or stage II squamous cell carcinoma of the head and neck to test the hypothesis that lymphocytic chromatid breaks induced by benzo[a]pyrene diol epoxide (BPDE), a tobacco mutagen, may also be associated with risk of developing cancers of the upper aerodigestive tract. METHODS: Case subjects were matched to control subjects on the basis of age, sex, ethnicity, and smoking status. Primary lymphocytes from 67 case subjects and 81 control subjects were treated with 2 microM BPDE for 24 hours, and the frequency of induced chromatid breaks was determined. All statistical tests were two-sided. RESULTS: Lymphocytes from case subjects compared with lymphocytes from control subjects showed significantly more breaks per cell induced by BPDE (mean+/-standard deviation, 0.77+/-0.38 versus 0.49+/-0.25; P<.001). Lymphocytes from 64.2% of case subjects were sensitive to BPDE (using a cutoff value of > or =0.60 break per cell). Subjects in the highest quartile of chromatid breaks had an approximately 20-fold increased risk of cancer compared with those in the lowest quartile after adjustment for age, sex, ethnicity, and smoking status. The association between BPDE sensitivity and cancer risk was higher in former smokers than in current smokers and higher in younger patients than in older patients. Subjects with sensitivity to both BPDE and bleomycin were at a 19.2-fold increased risk of cancer compared with those who were not sensitive to either agent. CONCLUSIONS: Mutagen sensitivity assays may aid in identifying individuals at risk of cancer, and use of parallel assays with two mutagens may improve risk predictability.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1998

Information sources and barriers to cancer treatment by racial/ethnic minority status of patients.

BACKGROUND: This study examined the sources used by cancer patients to obtain helpful information regarding their treatment options and side effects and the major predictors that facilitated usage of information. METHODS: The survey was administered to a representative sample of cancer patients in Texas. The cancer treatment facilities from which the patients were sampled were part of the University of Texas M. D. Anderson Cancer Center's Texas Community Oncology Network. A total of 593 patients (65%) out of 910 contacted responded to the survey. RESULTS: The patients reported that providers such as physicians and nurses were the most helpful sources of information. White patients tended to use books and reference materials more heavily to gather additional information regarding their treatment, while black patients relied on pamphlets and television. Educational level appeared to have a major influence on the black patient's use of printed materials. CONCLUSIONS: The results document the important role that providers play in influencing patients' treatment decisions. Effective ways to communicate with cancer patients are different for patients with different racial backgrounds. Implications for the future development of patient education materials and cancer prevention initiatives targeting ethnic minorities are addressed.

Adult↗

PubMed1998

The NCCN guideline program--1998.

In 1995, the National Comprehensive Cancer Network (NCCN) embarked on an ambitious project to develop comprehensive diagnostic and treatment algorithms for the broad spectrum of oncologic diseases and support modalities. To date, 28 NCCN guideline panels have developed guidelines covering an estimated 93% of tumors, and an additional 9 panels have guidelines under development. This article reviews the NCCN guideline infrastructure and development process. The process relies on the expertise of the 17 NCCN member institutions and follows a formal procedure for guideline development to ensure that the recommendations offer the cancer patient the best chance for a successful outcome.

Humans↗

PubMed1998

Guidelines and disease management.

The four NCCN Guidelines that follow represent the initial deliberations of an institutionally diverse, multidisciplinary panel comprised of internationally recognized experts. These experts have attempted to address the broad range of clinical decisions that oncologists face as they attempt to manage a patient with a particular tumor. The goal of the NCCN guidelines program is to publish comprehensive pathways that will serve as a foundation for all cancer care providers to develop superior disease management programs.

Disease Management↗

PubMed1997

Characterization and phylogenetic significance of rhinoceros luteinizing hormone beta (LHbeta) subunit messenger RNA structure, complementary DNA sequence and gene copy number.

The luteinizing hormone (LH) beta subunit gene is expressed in the pituitary glands of all mammals, whereas the closely related chorionic gonadotropin (CG) beta subunit genes have been identified only in primates and equids, and are expressed in placenta. In the case of horses, there is a single-copy equine (e) luteinizing hormone/chorionic gonadotropin hormone beta subunit gene (eLH/CGbeta) that (1) is expressed in both pituitary gland and placenta, (2) encodes a characteristic carboxyl terminal peptide (CTP) extension, and (3) transcribes an atypically elongated 5'-untranslated region (UTR) in both pituitary and placenta. However, it is not known whether similar expression patterns and gene locus characteristics may be exhibited by other members of the order Perissodactyla (equid, rhinoceros and tapir species). To begin to investigate these possibilities, we undertook analysis of the rhinoceros (rn or rhino) LH/(CG?)beta gene locus and the rnLHbeta cDNA. Total RNA isolated from the pituitary gland of a female white rhino was used as template for amplifying rnLHbeta cDNA by reverse transcription-polymerase chain reaction. Following cloning of the amplified cDNA, nucleotide (nt) and deduced amino acid sequences were determined. The first in-frame stop codon occurred at codon position +122, suggesting that the rnLHbeta subunit does not contain a CTP. To assess gene copy number, Southern blot analysis of Indian rhino genomic DNA was performed. The resulting simple hybridization pattern indicated that, as in the horse and donkey, there is a single-copy gene at the rnLH/(CG?)beta gene locus. Primer extension mapping of the pituitary transcriptional start site of the rnLHbeta subunit gene revealed an 8 nt 5'-UTR which is similar to that reported for the majority of mammalian LHbeta transcripts. Northern analysis was consistent with the transcriptional start site findings. We postulate from these data that rhinos diverged from equids prior to the occurrence of the mutations causing CTP expression and adoption of a non-consensus 5'-UTR/proximal promoter region. However, these findings do not rule out the possibility of expression of a placental CGbeta subunit lacking a CTP in rhinos.

Amino Acid Sequence↗

PubMed1997

Evidence that endogenous relaxin promotes growth of the vagina and uterus during pregnancy in gilts.

Recently, it was demonstrated that endogenous relaxin promotes growth of the vagina during the second half of pregnancy in rats and that administration of porcine relaxin promotes growth of the uterus in nonpregnant or early pregnant gilts. This study examined the effects of circulating relaxin on growth of both the vagina and uterus during the last two thirds of the 114-day gestation period in gilts. Furthermore, this study employed an in vitro immunohistochemical localization technique to determine whether the vagina and uterus in pigs have specific relaxin-binding sites. Three groups of pregnant gilts were used: sham-ovariectomized controls (group C; n = 8), ovariectomized progesterone-treated (group OP; n = 6), and ovariectomized progesterone- plus relaxin-treated (group OPR; n = 7). Gilts were either sham ovariectomized or ovariectomized on day 40 of gestation. Hormone replacement therapy with progesterone (group OP), progesterone plus relaxin (group OPR), or hormone vehicles (group C) began on day 38 (progesterone) or day 40 (relaxin) and continued until day 110. On day 110, the vagina and uterus were collected, and wet weight, dry weight, and percent hydration were determined. Small pieces (2-3 cm3) of the vagina and uterus from groups C and OP were frozen and cryosectioned for the immunohistochemical localization of relaxin-binding sites. Relaxin promoted growth of both the vagina and uterus. The wet weights of both the vagina and uterus in relaxin-deficient gilts (group OP) were lower (P < 0.05) than those in controls (group C), and relaxin replacement therapy (group OPR) restored the wet weights of both tissues to values that did not differ from those in controls. The mean dry weights and percent hydrations in the vagina and uterus did not differ among treatments. Immunohistochemical localization studies in the vagina and uterus demonstrated that specific and saturable binding of relaxin was localized in the same cell types of both tissues, namely epithelial cells (luminal in vagina, and both luminal and glandular in uterus), smooth muscle cells (both circular and longitudinal in vagina, and myometrial in uterus), and cells associated with blood vessels. In conclusion, this study provides evidence that circulating relaxin promotes growth of both the vagina and uterus during pregnancy in the pig. Furthermore, this study provides evidence that both the vagina and uterus contain specific and saturable relaxin-binding sites in epithelial cells, smooth muscle cells, and cells associated with blood vessels. We conclude that these cells probably initiate relaxin's effects on the vagina and uterus of the pregnant pig.

Animals↗

PubMed1997

The NCCN Guideline Program: a conceptual framework.

The goal of the National Comprehensive Cancer Network (NCCN) in developing clinical practice guidelines is to provide oncologists with guidance in making difficult clinical decisions. Since the data to make evidence-based decisions are often unavailable, the NCCN method attempts to integrate expert opinion into the process, striving to use that opinion in the most unbiased and reasonable manner through the diversity of its panels and the use of reiterative feedback loops. The development of oncology guidelines is a dynamic process. Each year the NCCN anticipates that the expert opinion elements of the guidelines will either be validated by clinical trial evidence or replaced by newer, sounder approaches.

Decision Making↗

PubMed1997

Baseline institutional compliance with NCCN guidelines: non-small-cell lung cancer.

To assess current physician practice patterns and whether they comply with guidelines published by the National Comprehensive Cancer Network (NCCN), we performed a retrospective review of 107 consecutive patients who underwent pulmonary resections for non-small-cell lung cancer at M. D. Anderson Cancer Center. Compliance with the guidelines was examined at four points in the patient's care: (1) preoperative work-up and evaluation, (2) operation performed and pathologic review, (3) postoperative adjuvant care, (4) routine follow-up and surveillance. Deviations from the guidelines were most marked in the preoperative evaluation phase. Excessive screening for metastases was performed in nearly 50% of the patients. Mediastinoscopy was appropriately utilized (according to the NCCN guidelines) in 93% of the patients, and appropriate anatomic resections and mediastinal nodal dissections were performed in 96% of the thoracotomies. Adjuvant care followed the NCCN recommendations in all patients. Excessive radiographic testing in asymptomatic patients was again seen in the postoperative surveillance program. Based on these findings, as well as the results of a previous evaluation of the cost-effectiveness of follow-up care in patients with resected lung cancers, we conclude that more widespread adherence to the radiographic recommendations in the NCCN guidelines would result in significant institutional and national health-care savings.

Carcinoma, Non-Small-Cell Lung↗

PubMed1996

Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers.

Introduction of tumor markers into routine clinical practice has been poorly controlled, with few criteria or guidelines as to how such markers should be used. We propose a Tumor Marker Utility Grading System (TMUGS) to evaluate the clinical utility of tumor markers and to establish an investigational agenda for evaluation of new tumor markers. A Tumor Marker Utility Grading Worksheet has been designed. The initial portion of this worksheet is used to clarify the precise characteristics of the marker in question. These characteristics include the marker designation, the molecule and/or substance and the relevant alteration from normalcy, the assay format and reagents, the specimen type, and the neoplastic disease for which the marker is being evaluated. To determine the clinical utility of each marker, one of several potential uses must be designated, including risk assessment, screening, differential diagnosis, prognosis, and monitoring clinical course. For each of these uses, associations between marker assay results and expected biologic process and end points must be determined. However, knowledge of tumor marker data should contribute to a decision in practice that results in a more favorable clinical outcome for the patient, including increased overall survival, increased disease-free survival, improvement in quality of life, or reduction in cost of care. Semiquantitative utility scales have been developed for each end point. The only markers recommended for use in routine clinical practice are those that are assigned utility scores of "++" or " " on a 6-point scale (ranging from 0 to ) in the categories relative to more favorable clinical outcomes. Each utility score assignment should be supported by documentation of the level of evidence used to evaluate the marker. TMUGS will establish a standardized analytic technique to evaluate clinical utility of known and future tumor markers. It should result in improved patient outcomes and more cost-efficient investigation and application of tumor markers.

Biomarkers, Tumor↗

PubMed1996

Participants' perceptions of a phase I colon cancer chemoprevention trial.

To assess participants' perceptions of a phase I colon cancer chemoprevention trial using a calcium intervention, questionnaires were mailed to trial participants at the conclusion of the study. Responses to questionnaire items reported here include (1) perceived benefits and barriers of participation, (2) interest in participating in future trials, (3) willingness to pay trial expenses out of pocket, and (4) posttrial continuation of the calcium regimen. The study found that the most highly rated trial benefit was the perception of potential colon cancer prevention; the trial barrier reported to be the most troublesome was inappropriate or mistaken billing for study visits. Three fourths of the subjects expressed an interest in future trials of the same duration. For trials of longer duration, this percentage decreased to 66%. Approximately half did not object to participation in future trials involving placebos, and just over one third indicated that they would either definitely (8%) or probably (27%) have joined the calcium trial even if they had to pay some study expenses out of pocket. Over 90% indicated they would continue taking the calcium pills if calcium is shown to be effective. The level of perceived benefits was positively associated with reported interest in participating in future trials of the same and longer durations, and the level of reported difficulty with trial pills and procedures was inversely related to interest in future placebo-controlled trials. The results of this study, in conjunction with results of prospective studies of trial participation, may be applied in future chemoprevention trials to facilitate recruitment, reduce attrition, and promote positive trial experiences for participants by emphasizing frequently reported benefits and minimizing frequently reported barriers.

Adenocarcinoma↗

PubMed1996

Prenatal alcohol and stress interact to attenuate ejaculatory behavior, but not serum testosterone or LH in adult male rats.

Restraint stress reduced blood alcohol levels in pregnant rats given a liquid alcohol diet. The male offspring prenatally exposed to both stress and alcohol failed to ejaculate spontaneously, although they copulated normally following exogenous testosterone (T) administration. Males prenatally exposed only to alcohol or only to stress showed no behavioral deficits. Adult serum T and luteinizing hormone levels were normal in both of the fetal alcohol exposed male groups. It appears that the androgen threshold for ejaculatory behavior is elevated in males prenatally exposed to alcohol plus stress and cannot be realized with normal testosterone titers, but it can be attained with exogenous hormone administration. Presumably the alcohol and stress combination interfered with ontogenetic patterns of T needed to fully masculinize the fetal nervous system.

Animals↗

PubMed1996

Calcium supplementation modifies the relative amounts of bile acids in bile and affects key aspects of human colon physiology.

Use of calcium supplements has increased dramatically in recent years yet little is known about the effect of calcium supplementation on colon physiology. We supplemented 22 individuals with a history of resected adenocarcinoma of the colon, but currently free of cancer, with 2000 or 3000 mg calcium for 16 wk. The effects of supplementation on duodenal bile acids and important fecal characteristics including total fecal output, wet and dry weight, pH, bile acids (in solids and in fecal water), and concentrations and total excretion of calcium, magnesium, phosphates (organic and inorganic), unesterified fatty acids and total fat were determined. Calcium supplementation significantly decreased the proportion of water in the stool (P = 0.03), doubled fecal excretion of calcium (P = 0.006), and increased excretion of organic phosphate (P = 0.035) but not magnesium. Calcium supplementation significantly decreased the proportion of chenodeoxycholic acid in bile (P = 0.007) and decreased the ratio of lithocholate to deoxycholate in feces (P = 0.06). The concentration of primary bile acids in fecal water decreased after 16 wk Ca supplementation. Together with other reports of a "healthier" bile acid profile with respect to colon cancer when changes such as those observed in this study were achieved, these results suggest a protective effect of calcium supplementation against this disease.

Adenocarcinoma↗

PubMed1996

Effects of relaxin on lactational performance in ovariectomized gilts.

In gilts, mammary lobulo-alveolar growth begins on about Day 80 of gestation and continues progressively until term. Relaxin in concert with estrogen plays a major role in promoting this mammary gland growth. The present study was conducted to determine the importance for lactational performance of prepartum relaxin-dependent growth of the mammary glands in ovariectomized gilts given progesterone to maintain pregnancy. Twenty-four gilts were either sham ovariectomized or bilaterally ovariectomized and assigned to four treatment groups: sham-ovariectomized control, ovariectomized progesterone-treated, ovariectomized progesterone- and (starting at Day 80) relaxin-treated, and ovariectomized progesterone- and (starting at Day 100) relaxin-treated. Piglets were delivered by cesarian section, and gilts were given uniform colostrum-replete foster litters (born of untreated mothers) to nurse from Day 1 to Day 28 of lactation. Prepartum mammary development appeared by visual examination to be greatly reduced in relaxin-deficient gilts. Stimulus of the mammary nipples by the nursing piglets, however, appeared to overcome relaxin-dependent differences in mammary development among treatments. There was no effect of treatment on the time piglets spent at the udder, piglet mortality, piglet weight at Day 21 of lactation, milk composition, mammary cross-sectional area, or sow weight change during lactation. We conclude that gilts devoid of circulating luteal relaxin can display normal lactational performance when given colostrum-replete foster litters.

Animals↗

PubMed1996

Use of hematopoietic colony-stimulating factors: the American Society of Clinical Oncology survey. The Health Services Research Committee of the American Society of Clinical Oncology.

PURPOSE: Dissemination of use of the hematopoietic colony-stimulating factors (CSFs) is unprecedented in oncology, with almost all physicians having experience with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) shortly after the drugs received Food and Drug Administration (FDA) approval in 1991. The American Society of Clinical Oncology (ASCO) Health Services Research Committee sought to assess patterns of use of CSFs before dissemination of its first-ever publication of ASCO guidelines. METHODS: A questionnaire describing clinical scenarios was mailed to American oncologists and hematologists who practice medical oncology. In each scenario, the physician was asked whether he would prefer to use a CSF to prevent or treat neutropenia. RESULTS: The response rate to the mailed survey was 49% (N = 475). Most physicians preferred to use CSFs for secondary prophylaxis in patients receiving chemotherapy at rates of 44% to 85%, rather than reduce doses. Patterns of use did not differ for palliative, curative, or adjuvant chemotherapy. While the majority of CSF patterns of care were similar to those recommended in the ASCO guidelines, more than half of the physicians chose to use CSFs in the treatment of febrile neutropenia, an area not supported in the subsequent guidelines. In general, physicians at academic medical centers and in Health Maintenance Organization (HMO) practices were more likely to prefer dose-reduction strategies over addition of CSFs, while fee-for-service physicians preferred the opposite strategies. CONCLUSION: Variations in CSF preferences for use were related to differences in clinical characteristics (history of afebrile v febrile neutropenia), drug characteristics (G-CSF or GM-CSF), and physician practice characteristics (HMO or fee-for-service setting). However, before dissemination of the guidelines, the majority of American oncologists preferred strategies that were subsequently included in the ASCO CSF guidelines. CSF guidelines would be most likely to reduce CSF use for treatment of afebrile and uncomplicated febrile neutropenia.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Barriers to cancer treatment: a review of published research.

PURPOSE/OBJECTIVES: To review published research on barriers to cancer treatment to provide a foundation for subsequent research and program and policy development directed at diminishing these barriers. DATA SOURCES: Relevant literature from medical and behavioral science data bases published between 1964 and 1994. Researchers reviewed 752 abstracts; they identified 160 articles that related directly to research on barriers to cancer treatment. Of these 160 articles, researchers chose 61 for a subsequent review using criteria to evaluate the strength of the study design and sampling procedures. DATA SYNTHESIS: The major barriers consistently documented to influence whether or not patients with cancer sought or continued treatment included communication problems between patients and providers, lack of information on side effects, cost of treatment, difficulties in obtaining and maintaining insurance coverage, and absence of social support networks. Access barriers generally were greater for older women, members of minority groups, and patients of lower socioeconomic status. The vast majority of the studies were conceptual or descriptive in nature and were based on nonprobability clinic-based samples. CONCLUSIONS: The limitations of existing research point to the need for studies on barriers to cancer treatment based on analytic population-based study designs that examine the relative importance of factors derived from multivariate explanatory models. This information may be used to develop programs and policies to ameliorate treatment barriers for patients with cancer. IMPLICATIONS FOR NURSING PRACTICE: The research priorities set forth by the Oncology Nursing Society also indicate a need for this type of research because quality of life, cost containment, and outcomes assessment all are directly or indirectly affected by the timely diagnosis of cancer. Treatment barriers have the potential to significantly affect an individual's ability to seek care and ultimately to increase the cost of care associated with adverse outcomes that may result from delays in seeking treatment.

Female↗

PubMed1996

The NCCN Guidelines Development Program.

The National Comprehensive Cancer Network (NCCN) has begun a program for the development of comprehensive clinical practice guidelines for the management of the most common tumors. The NCCN guidelines reflect a process of consensus that relies on evaluation of the evidence and structured feedback. The guidelines are designed to reflect clinical decision-making, and attempt to deal with the complexity of managing cancer. The initial guidelines effort has yielded eight guidelines for adult cancers and three for pediatric cancers. The guidelines are set up in algorithm format. The NCCN members believe that clinical trials are always an appropriate form of patient management, and that the inclusion of a patient in a clinical trial is preferred at every decision point in the algorithm.

Clinical Trials as Topic↗

PubMed1996

Evaluation of preliminary NCCN guidelines by external review.

The National Comprehensive Cancer Network (NCCN) guidelines development process is based on a system of iterative review. In addition to review of the preliminary guidelines by member institutions, we surveyed attendees at the NCCN's First Annual Conference about the appropriateness of the guidelines recommendations. After each presentation session, a broad range of health-care professionals, including non-NCCN academic and community oncologists and corporate and third-party representatives, completed a survey instrument. In this article, we summarize and comment on the results of these surveys.

Humans↗