Biomedical subjects

R J Winn

Publications and source records attributed to R J Winn.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1995

Randomized phase III study of 5-fluorouracil plus high dose folinic acid versus 5-fluorouracil plus folinic acid plus methyl-lomustine for patients with advanced colorectal cancer.

BACKGROUND: Metastatic colorectal cancer is generally incurable. The most active regimen available, 5-fluorouracil (5-FU) and folinic acid (Leucovorin), produces response rates of approximately 25% to 30%. Methyl-lomustine is a nitrosourea with modest activity against colorectal cancer. A randomized trial was undertaken to evaluate the impact the addition of methyl-lomustine would have on response, duration of survival, and survival rates in patients with advanced colorectal cancer. METHODS: The methyl-lomustine/5-FU/Leucovorin (MFL) regimen consisted of methyl-lomustine (110 mg/m2), administered on Day 1 of each 8-week cycle with six weekly boluses of 5-FU (600 mg/m2), and Leucovorin (500 mg/m2). The FL treatment arm consisted of the administration of 5-FU and Leucovorin as described above. Patients were evaluated for response and toxicity after each 8-week cycle. RESULTS: Of 319 patients included in this trial, 297 (93.1%) had disease evaluable for response and toxicity: 145 received MFL, and 152 received FL. In this trial, 526 courses of MFL and 529 courses of FL were administered. Methyl-lomustine/5-FU/Leucovorin treatment resulted in 4 complete and 30 partial responses (response rate, 21.9%), and FL treatment resulted in 9 complete and 33 partial responses (response rate, 26.4%). There was no significant difference in median survival duration between patients in the two arms (MFL = 48 weeks, FL = 51 weeks). However, MFL was significantly more toxic with greater myelosuppression than was FL (Grade 3-4 neutropenia: MFL = 56 patients, FL = 27 patients, P < 0.001; Grade 3-4 thrombocytopenia: MFL = 49 patients, FL = 2 patients, P < 0.001; Grade 3-4 anemia: MFL = 15 patients, FL = 6 patients, P < 0.001; and more prolonged median duration of granulocytopenia: MFL = 9 days, FL = 7 days, P < 0.001; and thrombocytopenia: MFL = 14 days, FL = 7.5 days, P < 0.001). CONCLUSION: Because the addition of methyl-lomustine in the MFL schedule markedly increased the toxicity of the regimen and because the FL regimen was as effective as MFL, the authors recommend that Leucovorin and 5-FU remain the treatment choice for treating patients with metastatic colorectal cancer.

Adult↗

PubMed1995

Phase II study of carboplatin and continuous infusion bleomycin followed by cisplatin and 5-fluorouracil in recurrent head and neck cancer.

BACKGROUND: Recurrent squamous cell carcinoma of the head and neck is poorly responsive to most chemotherapy regimens. Carboplatin and bleomycin are effective single agents with non-overlapping toxicity; therefore, we sought to explore the efficacy of this regimen in a phase II study. In the second stage of the study, patients who did not respond to carboplatin and bleomycin were given treatment with cisplatin and 5-fluorouracil (5-FU). PATIENTS AND METHODS: Patients with recurrent squamous cell carcinoma of the head and neck were treated with carboplatin 400 mg/m2 followed by bleomycin 15 units intravenously as a continuous infusion for 4 days. Patients with no tumor response after 3 cycles of carboplatin and bleomycin were crossed-over to receive cisplatin 100 mg/m2 and 5-FU 1000 mg/m2/day continuous infusion for 5 days. RESULTS: Among the 20 carboplatin-bleomycin patients evaluable for toxicity, no cases of grade 4 granulocytopenia were reported and grade 3 or 4 thrombocytopenia developed in only three patients. Three partial responses occurred among the 19 patients (16%) [95% C.I. 0% to 32%] evaluable for response to carboplatin-bleomycin. None of the 11 patients crossed-over to cisplatin and 5-FU had a major response. CONCLUSION: The combination of carboplatin and bleomycin is well tolerated in patients with recurrent head and neck cancer, but the activity does not appear to be superior to the activity of either agent alone. Patients who did not respond to carboplatin and bleomycin were also resistant to the cisplatin and 5-FU regimen.

Adult↗

PubMed1995

Effects of relaxin administration in early gestation or prior to mating on uterine length and fetal survival in gilts.

The objective of this research was to determine the effect of administration of porcine relaxin to gilts during early gestation, or during the follicular phase of the estrous cycle immediately preceding mating, on the length of the uterus and consequently the number of surviving fetuses. Experiment 1 determined the individual and combined effects of 10 days of administration of relaxin (0.5 mg, 4 times daily), estradiol benzoate (1 mg, 2 times daily), and progesterone (50 mg, 2 times daily) on uterine wet weight and length in 58 ovariectomized 8-mo-old pubertal gilts. Relaxin alone had no effect on either uterine length or wet weight. Estrogen increased uterine wet weight, and this effect was augmented by relaxin. Progesterone increased uterine length, and this effect was augmented by estrogen. Combined treatment with progesterone, estrogen, and relaxin increased both uterine length and wet weight maximally. Experiment 2 determined the effects of relaxin administration in early gestation or prior to mating on uterine length and fetal survival in 75 unilaterally ovariectomized-hysterectomized gilts. Relaxin (0.5 mg, 4 times daily) was administered during three treatment periods, and uteri were collected on Day 40 of gestation. In this study, relaxin administration from Days 11 to 20 of gestation reduced the number of live fetuses (p = 0.01) and percentage survival (p = 0.01) and resulted in shorter uterine length (p = 0.01) and lower uterine wet weight (p = 0.03) than in controls, but did not affect length of uterus or uterine dry weight. Relaxin administration from Days 22 to 31 of gestation did not influence fetal survival, uterine length, uterine length per fetus, uterine wet weight, or uterine dry weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

A comparison of factors affecting aesthetic outcomes of TRAM flap breast reconstructions.

The aesthetic results of TRAM flap breast reconstructions were assessed in 237 consecutive breast cancer patients. Nine independent judges, none of whom were plastic surgeons or members of the reconstructive team, assigned an aesthetic score to each patient after viewing postoperative photographs. We found that bilateral reconstructions were aesthetically superior to unilateral reconstructions (p = 0.0013), that immediate reconstructions were aesthetically superior to delayed reconstructions (p = 0.0001), and that previous irradiation of the chest wall reduced the mean aesthetic score (p = 0.0010). We also found that the mean aesthetic score assigned to patients who had reconstructions with free TRAM flaps was superior to that assigned to those who had reconstructions with conventional TRAM flaps, but when tested by multiple regression analysis, this trend was not statistically significant (p = 0.2972).

Breast↗

PubMed1995

The role of oncology clinical practice guidelines in the managed care era.

The development of clinical practice guidelines in oncology presents unique problems and challenges due to the heterogeneity of disease presentations and the complexity of therapeutic decisions. Guidelines should incorporate not only standard outcomes measures such as survival but, if feasible, quality of life measures, patient preferences, and cost-effectiveness analyses. Although clinical guidelines are being promulgated as a means of assisting physicians in making therapeutic decisions, another purpose of guidelines implementation reflects the goals of managed care, ie, to promote practice conformity and reduce the cost of care. Methods to monitor physicians' adherence to guidelines are expected to increase as a means of ensuring compliance. This article reviews the process of developing two common types of guidelines used in oncology: path guidelines (using stage II breast cancer as a paradigm) and boundary guidelines (such as the ASCO growth factor guidelines).

Humans↗

PubMed1995

Current status of practice guidelines in oncology.

A large number of organizations are currently developing practice guidelines in oncology. These include federal agencies; medical societies and groups, including both oncologic and nononcologic specialty societies; and informal and formal groups of oncologists at the national, regional, and local level. Despite this marked increase in guideline activity, the science of guideline development must still be considered embryonic. Several general principles appear to be important for the generation of sound practice guidelines: (1) selection of suitable topics; (2) appropriate composition of the panel; (3) objectivity of the process used to arrive at recommendations; and (4) specific provisions for review and revision. Like the science of guideline development, the science of guideline implementation is still in its infancy. The factors facilitating physician acceptance of guideline recommendations have yet to be identified. Also, systematic evaluation of the effectiveness of different implementation strategies is needed.

Government Agencies↗

PubMed1994

Phase II trial of piroxantrone in metastatic gastric adenocarcinoma.

Piroxantrone, a synthetic intercalating agent, was studied in patients with advanced, measurable gastric adenocarcinoma who had not received prior chemotherapy. The starting piroxantrone dose was 150 mg/m2 given intravenously over 1 hour on day 1 and repeated every 21 days. Response and toxicity could be evaluated in 15 patients. No complete, partial, or minor responses were observed. Toxic effects included granulocytopenia, anemia, vomiting, nausea, anorexia, fatigue, stomatitis, alopecia, hyperbilirubinemia, and increased alkaline phosphatase levels. At the stated dose and schedule, piroxantrone does not possess significant activity against advanced gastric cancer.

Adenocarcinoma↗

PubMed1994

Male and female sexual behavior potential of male rats prenatally exposed to the influence of alcohol, stress, or both factors.

Adult sexual behaviors were characterized in male rats prenatally exposed to ethanol, stress, or ethanol combined with stress; 60% to 75% of each group exhibited female-typical lordosis. A substantial proportion of males subjected to alcohol (44%) or to alcohol with stress (54%) failed to ejaculate. The adult genitalia and testicular size appeared normal in all groups. Either alcohol or stress can suppress fetal plasma testosterone. Thus, exposing pregnant dams to alcohol, particularly in association with stress, may alter the hormonal milieu of their male fetuses sufficiently to block full masculinization and defeminization of sexually dimorphic copulatory behavior potentials, but not anatomy. It appears that certain pharmacological and stressful factors can interact during fetal ontogeny to influence the process of sexual behavior differentiation.

Animals↗

PubMed1994

Phase II trial of edatrexate in patients with advanced pancreatic adenocarcinoma.

BACKGROUND: The methotrexate analogue 10-ethyl-10-deazaaminopterin (10-EdAM, or edatrexate) has shown antitumor activity in preclinical testing and clinical studies of patients with breast, lung and head and neck carcinomas. A phase II study was conducted in patients with advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Forty patients were enrolled on the clinical trial. Edatrexate was administered intravenously at a dose of 80 mg/m2 weekly for 5 weeks. The treatment course was repeated every 6 weeks. RESULTS: Two partial responses were observed. Both of these patients had partial responses which lasted 2 and 3.5 months. The median survival for all patients was 3.5 months. Serious (grade 3 or 4) toxic effects were primarily mucosal, hematologic, and dermatologic. Two patients experienced severe pulmonary toxic reactions. CONCLUSION: At the dose and schedule used, edatrexate was poorly tolerated and did not demonstrate significant antitumor activity.

Adenocarcinoma↗

PubMed1994

Phase II trial of edatrexate in patients with advanced hepatocellular carcinoma.

BACKGROUND: The methotrexate analogue edatrexate (10-ethyl-10-deaza-aminopterin, or 10-EDAM) has demonstrated greater activity than methotrexate has against murine tumors and human tumor xenografts. Phase II trials of edatrexate have already demonstrated its activity against breast, lung, and head and neck carcinomas. A phase II trial of edatrexate was conducted in patients with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Seventeen patients with previously untreated unresectable hepatocellular carcinoma were enrolled on the study. Edatrexate, 80 mg/m2 weekly for 5 weeks, was administered intravenously. The treatment course was repeated every 6 weeks. Tumor response was evaluated by computerized tomographic scan after 2 courses. RESULTS: No complete or partial responses were observed in this trial. Two minor responses, each lasting less than 12 weeks, were observed. Twelve patients had elevated serum alpha-fetoprotein (AFP) levels at entry into the study; 4 of the 12 patients experienced a > or = 25% decrease in the level of this tumor marker; 3 of the 4 had a > 50% reduction in AFP level. Grade 3 and 4 toxic effects were granulocytopenia, thrombocytopenia, anemia, oral mucositis, skin reactions, fatigue, anorexia, and diarrhea. CONCLUSIONS: Edatrexate administered at this dose and schedule appears to have little therapeutic efficacy against advanced hepatocellular carcinoma.

Adult↗

PubMed1994

Individual and combined effects of relaxin, estrogen, and progesterone in ovariectomized gilts. I. Effects on the growth, softening, and histological properties of the cervix.

Marked growth and softening of the uterine portion of the cervix occur during the last third of the 115-day gestation period in the gilt. These changes in the cervix are temporally correlated with elevated blood levels of relaxin, estrogen, and progesterone. We recently demonstrated that relaxin plays a major role in promoting both the growth and softening of the cervix that occur in pregnant gilts. The roles of estrogen and progesterone in these cervical changes remain poorly understood. Accordingly, this study determined the influence of relaxin, estrogen, and progesterone, individually and in combination, on cervical growth and softening in gilts. Fifteen days after ovariectomy, six to nine nonpregnant, sexually mature gilts were assigned to one of the following eight treatment groups: ovariectomized controls, relaxin treated, estrogen treated, progesterone treated, estrogen plus relaxin treated, progesterone plus relaxin treated, estrogen plus progesterone treated, and progesterone plus estrogen plus relaxin treated. Treatment was given for 10 days, with doses of relaxin (0.5 mg, four times daily), estradiol benzoate (1 mg, twice daily), and progesterone (50 mg, twice daily) selected to provide blood levels resembling those between days 100-110 of gestation. The growth, softening, and histological characteristics of the cervices were determined. Treatment with relaxin significantly increased the growth and softening and altered the histological characteristics of the uterine portion of the cervix in the absence of steroid treatment. Estrogen treatment alone increased cervical growth, but when given in combination with relaxin, estrogen did not augment relaxin's ability to increase either cervical growth or softening. Progesterone alone had little or no effect on the growth or softening of the uterine portion of the cervix. Unexpectedly, when given in combination with relaxin, progesterone augmented markedly relaxin's effects on softening and alteration of the histological characteristics of the cervix. In conclusion, this study is consistent with recent reports that relaxin promotes both the growth and softening of the cervix in the pig. Additionally, this study provides evidence that estrogen and relaxin act independently to promote the growth of the cervix in gilts, whereas progesterone acts in concert with relaxin to promote softening of the cervix and a reduction in the organization and density of cervical collagen fibers. This study provides evidence that relaxin, estrogen, and progesterone all very likely play important roles in the modifications of the cervix that occur during late pregnancy in the gilt.

Animals↗