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Biomedical subjects

R Courtney

Publications and source records attributed to R Courtney.

15 recordsLinked to original sources
PubMed2006

Plasminogen activator inhibitor-1 promoter polymorphism is not associated with the aggressiveness of disease in prostate cancer.

AIMS: PAI-1 (plasminogen activator inhibitors-1) regulates plasminogen activation, and is related to tumour development. This study aims to test whether the promoter polymorphism in the PAI-1 gene is related to the aggressiveness of disease in prostate cancer. MATERIALS AND METHODS: In the present study, Taqman SNP genotyping assay was used to detect PAI-1 4G/5G polymorphism in DNA from paraffin-embedded tissues of 98 Caucasian patients with prostate cancer. RESULTS: The distribution of the genotypes is in Hardy-Weinberg equilibrium. The genotype had no statistically significant relationship with other prognostic factors. Similar risks for recurrence were seen in individuals with the 4G/4G and 4G/5G genotypes compared to those with 5G/5G genotype (odds ratio [OR] 2.65, 95% CI: 0.41-16.94, P = 0.30; OR = 2.19, 95% CI: 0.38-12.49, P = 0.38). CONCLUSION: We concluded that PAI-1 promoter polymorphism is not associated with the aggressiveness of disease in prostate cancer.

Aged↗
PubMed2006

Pharmacokinetics, safety, and efficacy of posaconazole in patients with persistent febrile neutropenia or refractory invasive fungal infection.

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (P = 0.0004) and 182% (P < 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (n = 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure.

Adult↗
PubMed2005

Posaconazole pharmacokinetics, safety, and tolerability in subjects with varying degrees of chronic renal disease.

Posaconazole is a triazole antifungal in development for the treatment of invasive fungal infections. The authors evaluated the pharmacokinetics and safety of posaconazole in healthy subjects and in those with mild (CL(CR) = 50-80 mL/min), moderate (CL(CR) = 20-49 mL/min), and severe chronic renal disease (CL(CR) <20 mL/min; receiving outpatient hemodialysis) (n = 6/group). Subjects received one 400-mg dose of posaconazole oral suspension with a standardized high-fat breakfast. For hemodialysis-dependent subjects, this dose was given on a nonhemodialysis day, and a second 400-mg dose was given 6 hours before hemodialysis. Blood samples were collected before dose and up to 120 hours postdose. For hemodialysis-dependent subjects following the second dose, additional samples (predialyzed and postdialyzed) were collected before, during, and after dialysis. There was no correlation between posaconazole pharmacokinetics and mild to moderate renal disease; the slopes of the linear regressions for creatinine clearance versus posaconazole AUC, C(max), CL/F, and t1/2 values were not significantly different from zero (P > .130). Mean CL/F values before and during hemodialysis were comparable. Furthermore, the difference in the predialyzed and postdialyzed posaconazole concentrations was only approximately 3%, supporting that posaconazole was not removed by hemodialysis. Protein binding was similar in all groups (approximately 98%) and was unaffected by hemodialysis. Posaconazole was generally well tolerated. One patient had elevated liver function test results that were not present at baseline and were thought to be possibly related to posaconazole. Results of this single-dose study indicate that dosage adjustments for patients with varying degrees of renal disease are not required.

Administration, Oral↗
PubMed2004

Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study.

Posaconazole is an antifungal with a wide-spectrum of activity against common and emerging fungal pathogens. In this randomised, open-label, two-way crossover study, the potential for drug interactions with posaconazole via the cytochrome P450 (CYP450) enzyme pathway was evaluated. Thirteen subjects received posaconazole tablets (2 x 100 mg) once daily for 10 days or no treatment; following a 14-day washout period, subjects were crossed over to the alternate treatment. The inhibition spectra of posaconazole were examined using a cocktail of the following probe substrates: caffeine (CYP1A2), tolbutamide (CYP2C8/9), dextromethorphan (CYP2D6 and total CYP3A4), chlorzoxazone (CYP2E1), and midazolam (hepatic CYP3A4). Except for midazolam, which was intravenously infused on Day 10, the cocktail probes were administered simultaneously on Day 9 during both treatment periods. Blood and urine samples were collected at specified times to quantitate probe substrates and/or metabolites. Based on insignificant differences in mean probe ratios, posaconazole did not inhibit CYP1A2, 2C8/9, 2D6, or 2E1. However, the midazolam AUC((tf)) was higher in the posaconazole than no-treatment group (93.4 n gh/ml versus 51.4 ng h/ml, P<0.01), indicating inhibition of hepatic CYP3A4. Drug interactions mediated by various CYP450 are common with the currently available triazole antifungals, however these results suggest that posaconazole may have an improved and more narrow drug interaction profile (CYP3A4 only) compared with other triazoles.

Adult↗
PubMed1999

Monitoring cytomegalovirus retinitis prevalence in an HIV-seropositive cohort: the assessment of improvements observed following the introduction of highly active antiretroviral triple therapy.

This paper concerns the ophthalmic assessment of patients with acquired immunodeficiency syndrome (AIDS) for a number of eye conditions and in particular cytomegalovirus (CMV) retinitis. CMV has been the most common opportunistic infection associated with AIDS and the leading cause of blindness among AIDS patients. There have been early indications of a widespread fall in CMV prevalence internationally following the introduction of a new highly active antiretroviral triple (HAART) therapy. Our study sought to assess the position for Ireland. Our cohort was the entire population of stage IV AIDS patients attending the country's leading referral centre. The total number of patients examined was 167 and the period of examination was 1 May 1995 to 30 April 1997. HAART was introduced in March 1996, so the data permitted a 'before and after' comparison of various clinical findings. The incidence of new CMV cases was found to be 4 among the 102 patients examined in the first 12-month period and one among 107 patients examined in the second 12-month period. There were accompanying declines in HIV-related noninfectious retinal vasculopathy (HIVR), keratitis and other conditions. The findings are promising, but we argue that caution is needed in assessing long-term trends. In the paper we discuss a number of methodological issues in the collection and analysis of the clinical data and in the interpretation of results.

AIDS-Related Opportunistic Infections↗
PubMed1998

Increasing cultural competence with the Latino community.

There is growing recognition among health professionals that being familiar with the culture of a particular group and developing effective partnerships to involve group members in the production of their own health are essential strategies to promote health. Moreover, it is increasingly recognized that providing health care services that are culturally sensitive can result in improved health status for clients. This article describes selected Latino cultural customs that can enhance a nurse's ability to work sensitively and effectively with this ethnic group. Creative strategies to increase the cultural competence of nurses involved in primary care settings are also presented.

Community Health Nursing↗
PubMed1997

Investigation of nurse practitioner-patient interactions: using the Nurse Practitioner Rating Form.

Primary care has become a major focus of health care reform. To create the most effective delivery of primary care services by nurse practitioners (NPs), researchers, clinicians, and administrators must continue to develop knowledge about the structure, process, and outcomes of NP primary care patient encounters. Few measures of NP-patient care encounters exist. This exploratory study examines a method of investigating NP practice and a description of the process of NP primary care. The Nurse Practitioner Rating Form (NPRF) was used to analyze 20 videotaped NP visits with Latino clients in a primary care setting. Major findings are that NPs spent visit time engaged in assessment (61%), management (29%), and charting, consultation, and other (10%). The content or focus of the majority of NP time during visits (90%) was directed to existing physical problems. NPs received high scores for communication style and degree of client participation. Problems with using the NPRF are noted and key recommendations are made to enhance NP care and improve investigation of primary care practice.

Adolescent↗
PubMed1996

Localization of proliferating cell nuclear antigen in the developing and mature rat heart cell.

BACKGROUND: The cardiac muscle cell ceases to divide shortly after birth; this cessation is followed by a limited period when DNA synthesis and karyokinesis occur without cytokinesis. The regulation of this process is not known. The purpose of this study is to explore the possible events that could lead to the cessation of cardiac muscle cell division. One protein requisite for DNA synthesis is proliferating cell nuclear antigen (PCNA). This protein is the auxiliary protein of DNA polymerase delta. METHODS: Rats of fetal age day 18 or days 0, 4, 8, 12, and 16 after birth were obtained. In addition, adult hearts were used for this study. Hearts from the fetal day-18 rats and the day-0 neonatal rats were digested. Cardiac myocytes were isolated and placed in culture for an analysis of DNA synthesis by using tridiated thymidine. Ventricular muscle tissue was isolated from hearts of all ages and frozen in liquid nitrogen for Northern and Western blot analyses. RESULTS: Tridiated thymidine analysis revealed that, although serum stimulation significantly increased the number of labeled fetal cardiac muscle cells, it did not have that effect on neonatal cardiac muscle cells in culture. Northern blot analysis revealed that the steady state levels of mRNA for PCNA remained constant from fetal day 18 through day 4 after birth. Steady state levels declined during the second postnatal week and then reached basal levels by day 16. PCNA message was still present in adult heart tissue. By using indirect immunofluorescence and Western blotting, PCNA protein could be located in the nucleus of cardiac muscle cells during the first 2 weeks after birth. At 16 days after birth, the protein was found in the cytoplasm in very low amounts but was not found in the nucleus. The protein was barely detectable by Western blotting in the cytoplasmic fraction from the adult myocardium. CONCLUSIONS: The results of this study suggest that the PCNA message and protein product declined after birth, but both were present at low levels in the adult myocardium. However, the PCNA protein was not translocated to the nucleus in adult myocardial cells. The events involving PCNA correlated closely with the time period when cell division and then DNA synthesis ceased in these cells.

Aging↗
PubMed1996

The partnership model: working with individuals, families, and communities toward a new vision of health.

Increasingly, health professionals must learn to work in new partnership relationships with clients and community to promote health effectively. A partnership requires a transformation of the professional role from chief actor to partner, and the client role from passive recipient to partner. A partnership approach has particular merit in a reformed health care system that increasingly emphasizes active involvement and self-care actions of individuals and families to maintain health and prevent disease. A partnership approach is also important to professionals working with underserved, vulnerable, and/or minority populations. For too long professionals and policymakers have relegated these groups to passive roles in health decision making and action. This article will provide a description of the partnership process as it has been developed and implemented by nurse practitioners in an urban Hispanic community with emphasis on a community partnership. A partnership model is described and compared to the more traditional professional model. A definition and essential criteria for partnership are presented. Finally, a specific example of how the partnership process was implemented at the community level is discussed.

Community Health Nursing↗
PubMed1995

Community partnership primary care: a new paradigm for primary care.

Primary care has become the focal point of health care reform. For too long primary care has been narrowly conceptualized as office-based care for common problems of individuals. In this article, a nurse practitioner describes a new model for primary care, community partnership primary care (CPPC), which moves beyond typical primary care practice to create what may be a new paradigm for primary care. This proposed new paradigm moves beyond older models of primary care into new dimensions of practice. The CPPC model emphasizes new roles for clinicians and a unique goal to foster the empowerment of individuals, families, and community. Innovative features of the CPPC model include blending a clinical role with a new area of practice called community practice. CPPC emphasizes new, innovative roles for nurse practitioners and nurses in community development and community empowerment activities. A 4-year funded project permitted the development and implementation of the CPPC model in an urban Hispanic community. This article provides an overview of the CPPC model and the initial steps of model implementation.

Community Health Services↗
PubMed1995

Using an encounter form to develop a clinical database for documenting nurse practitioner primary care.

A clinical database will enable nurse practitioners to document and improve characteristics of their practices. This information is vital if nurse practitioners expect to achieve success in the changing U.S. health care system. This article describes the process of creating an encounter form and a related clinical database. Changes made in a family practice clinic that were derived from using a clinical database are presented. Additional uses for a clinical database, such as quality assurance, clinical evaluation, and clinical research, are discussed.

Database Management Systems↗
PubMed1994

An immunohistochemical study of p53 and proliferating cell nuclear antigen expression in progressive multifocal leukoencephalopathy.

Nuclear p53 immunoreactivity is demonstrated in infected oligodendroglia, as well as in a proportion of reactive and bizarre astrocytes, in seven progressive multifocal leukoencephalopathy (PML) biopsies. This likely represents binding to, and prolongation of the half-life of, wild-type p53 protein by JC virus T-antigen. Other possible mechanisms are considered. The same cells show proliferating cell nuclear antigen (PCNA) positivity, as do a proportion of morphologically normal oligodendroglia and astrocytes, reflecting proliferating populations of these glial sub-types. It is possible that functional inactivation of p53 in nonlytically infected astrocytes may allow neoplastic astrocyte clones to emerge. However, p53 and PCNA immunoreactivity per se cannot be regarded as indicative of neoplasia in PML, and caution must be exercised in the interpretation of such nuclear staining profiles.

Adult↗