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C Nolan

Publications and source records attributed to C Nolan.

At least 19 recordsLinked to original sources
PubMed2006

Assessing procedural skills in context: Exploring the feasibility of an Integrated Procedural Performance Instrument (IPPI).

BACKGROUND: The assessment of clinical procedural skills has traditionally focused on technical elements alone. However, in real practice, clinicians are expected to be able to integrate technical with communication and other professional skills. We describe an integrated procedural performance instrument (IPPI), where clinicians are assessed on 12 clinical procedures in a simulated clinical setting which combines simulated patients (SPs) with inanimate models or items of medical equipment. Candidates are observed remotely by assessors whose data are fed back to the clinician within 24 hours of the assessment. This paper describes the feasibility of IPPI. RESULTS: A full-scale IPPI and 2 pilot studies with trainee and qualified health care professionals has yielded an extensive data set including 585 scenario evaluations from candidates, 60 from clinical assessors and 31 from simulated patients (SPs). Interview and questionnaire data showed that for the majority of candidates IPPI provided a powerful and valuable learning experience. Realism was rated highly. Remote and real-time assessment worked effectively, although for some procedures limited camera resolution affected observation of fine details. DISCUSSION: IPPI offers an innovative approach to assessing clinical procedural skills. Although resource-intensive, it has the potential to provide insight into individual's performance over a spectrum of clinical scenarios and at no risk to the safety of patients. Additional benefits of IPPI include assessment in real time from experts (allowing remote rating by external examiners) as well as provision of feedback from simulated patients.

Clinical Competence↗
PubMed2005

Elevated G2 chromosomal radiosensitivity in Irish breast cancer patients: a comparison with other studies.

Previous studies have shown that a significant proportion of breast cancer patients exhibit elevated G2 chromosomal radiosensitivity in contrast to controls (approximately 40%). In this study, the G2 assay was applied to a small number of Irish breast cancer patients who were recorded as sporadic cases and they were compared with a control group to compare and contrast with the previous documented studies. Lymphocyte cultures were set up on whole blood samples and stimulated with phytohaemagglutinin. The cultures were irradiated 74 h later with 0.5 Gy gamma-radiation and cells were arrested in metaphase by treating the cultures with colcemid. The chromosomes were harvested and the aberrations scored per 100 metaphases to assign a G2 score. The assay was first carried out on four donor controls to estimate intra-individual variation and then ten controls for inter-individual variation to measure assay reproducibility. The G2 assay was then applied to 27 breast cancer patients. Good intrinsic assay reproducibility was observed in the coefficient of variation (CV) data in three out of four controls. Intra-individual variation was similar in three out of four of the donors (4.6 - 5.1%) with one donor showing a higher CV compared with the others (22.9%). Inter-individual variation was calculated at 30.5% for all controls. No significant difference was observed between intra- and inter-individual variation using the variance ratio F-test. A G2 radiosensitivity cut-off of 110 aberrations/100 metaphases was calculated from the controls, and from this 70.4% of breast cancer patients and 7.7% of controls were calculated as G2 radiosensitive. This proportion of G2-sensitive breast cancer patients is the highest recorded in studies to date. It is thought that the G2 radiosensitivity assay is a biomarker of breast cancer predisposition genes of low penetrance, suggesting the presence of these genes in the Irish breast cancer patients used in this study who were recorded as sporadic cases. A larger number of Irish patients would be required to consolidate these findings and be representative of the Irish breast cancer population.

Adult↗
PubMed2003

Predictive testing for BRCA1 and 2 mutations: a male contribution.

BACKGROUND: Management strategies for women carrying BRCA1 and 2 mutations are becoming clearer and predictive testing for a known family mutation is commonly undertaken. Implications for men are not as clear and they participate less frequently. PATIENTS AND METHODS: Twenty-six men from 10 extended families underwent predictive testing. Their motivation, reaction and outcome were studied. Subjects had appropriate pre- and post-test counselling. Informed consent was obtained before predictive testing for known deleterious mutations. DNA analysis followed standard procedures. RESULTS: Eighteen tested positive and eight negative. Four had adverse psychological reactions and three reneged on their commitments to impart results. The spouse of another man had an adverse psychological reaction to the disclosure of his positive result. Two, already suffering from prostate cancer, were phenocopies and paternal lineage transmission was unexpectedly determined in another. Risk was removed from 33 offspring and confirmed for 56. CONCLUSIONS: Complex themes associated with genetic testing are confirmed and the spectrum extended. Men appear to understand the importance of participating in this process. Methods of avoiding adverse reactions merit further study along with other aspects of the process.

Adult↗
PubMed2001

Serum hormone levels in humans with low serum concentrations of 2,3,7,8-TCDD.

We measured current serum hormone and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in 37 men who sprayed 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in the State of Victoria, Australia. TCDD levels were consistently significantly inversely related to prolactin levels in all analyses. In correlation analyses, TCDD levels were also inversely related to triiodothyronine (T3), thyroid-stimulating hormone (TSH), and testosterone levels, and positively associated with glucagon levels. The mean serum TCDD concentration in these sprayers was between 2.6 and 8.1 parts per trillion (ppt). Since such TCDD levels are commonly found in the general population in countries such as the US, the results could suggest that background levels of TCDD in the general population could have an effect on hormone levels. The findings are preliminary and need to be replicated in order to evaluate their full public health significance.

Adult↗
PubMed1999

Comparable specificity of 2 commercial tuberculin reagents in persons at low risk for tuberculous infection.

CONTEXT: One or both commercial tuberculin skin test reagents (Aplisol and Tubersol) may have a high rate of false-positive reactions. OBJECTIVE: To compare the reaction size and specificity of skin testing with Aplisol, Tubersol, and the standard purified protein derivative (PPD-S1). DESIGN: Double-blind trial, conducted between May 14, 1997, and October28, 1997, in which each individual received 4 tuberculin skin reagents at sites assigned at random. SETTING: Health departments and universities in 6 US cities. PARTICIPANTS: A total of 1555 persons at low risk of latent tuberculosis infection. INTERVENTION: Simultaneous skin tests with Aplisol, Tubersol, PPD-S1, and either a second PPD-S1 or PPD-S2 (a proposed new standard). MAIN OUTCOME MEASURE: Reaction size at each injection site measured by 2 investigators blinded to type of reagent. RESULTS: Aplisol produced slightly larger reactions than Tubersol, but this difference did not significantly change skin test interpretation. The mean +/- SD reaction sizes were 3.4+/-4.2 mm with Aplisol, 2.1+/-3.2 mm with Tubersol, and 2.5+/-3.6 mm with PPD-S1. Assuming that all participants were uninfected and using a 10-mm cutoff, the specificities of the tests were high: Aplisol, 98.2%; Tubersol, 99.2%; and PPD-S1, 98.9%. Significant variability was not detected in interobserver, host, and lot-to-lot reagent comparisons. CONCLUSION: Using a cutoff of at least 10 mm, testing with 3 different PPD reagents resulted in similar numbers of uninfected persons being correctly classified.

Adult↗
PubMed1999

Decreased immunoexpression of prostate inhibin peptide in prostatic carcinoma: a study with monoclonal antibody.

Prostate inhibin peptide (PIP) is a follicle-stimulating hormone (FSH) regulating peptide produced by the prostate. The mechanism of its endocrine role in regulating prostate growth is believed to be androgen-independent but FSH-dependent. Previous studies using polyclonal antibody proposed PIP as a prostatic-specific marker in cancer diagnosis. However, the recently available monoclonal antibody has not yet been evaluated. Paraffin sections of 72 prostatectomy specimens for prostate cancer with or without hormonal blockage therapy and 10 nonneoplastic prostate tissues from autopsy were stained by using PIP monoclonal antibody (clone: 4A6A6) with the avidin-biotin complex method. PIP reactivity was semiquantitatively estimated in prostatic carcinoma (PCA), prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal tissue in each case when ever present. Statistical analyses were performed accordingly. PIP expression is predominantly cytoplasmic. Urothelium, seminal vesicles, inflamed prostatic glands, basal cells, and squamous metaplasia were negative for PIP. Average percentage of cells expressing PIP was significantly decreased in PIN (40%) and PCA (14%) when compared with BPH (81%) and normal tissue (68%). There was no correlation of tumor PIP level with patient's age, tumor size, Gleason score, tumor stage, or the usage of preoperative hormonal blockage therapy. PIP monoclonal antibody should be used with caution as a prostate-specific marker in surgical pathology. The mechanism for this alteration and the effect of PIP on prostatic tumor growth, particularly in patients under a variety of hormonal therapies, needs further study.

Adult↗
PubMed1999

An exploration of the preceptor role: preceptors' perceptions of benefits, rewards, supports and commitment to the preceptor role.

This Australian study, a replication of Canadian research by Dibert & Goldenberg, was undertaken to explore the relationship between preceptors' perceptions of benefits, rewards and support, and their commitment to the preceptor role. A convenience sample of 134 nurse preceptors involved in an undergraduate nursing course were invited to complete a four-part questionnaire consisting of the Preceptor's Perception of Benefits and Rewards Scale, the Preceptor's Perception of Support Scale, the Commitment to the Preceptor Role Scale, and demographic details. The results, in the main, parallel those of the original research, with differences reflecting the distinct nature and the more recent use of preceptorship in Australia. The results indicate a clear commitment to the preceptor role and a perception that both material and non-material benefits are derived from acting in the role. Additionally, support from the institution and coworkers was considered vital for participation in the role. This not only has implications for nursing educators, administrators and potential preceptors, but also for those being preceptored.

Adult↗
PubMed1997

Mycophenolate mofetil decreases rejection in simultaneous pancreas-kidney transplantation when combined with tacrolimus or cyclosporine.

BACKGROUND: Historically, the acute rejection rates in simultaneous pancreas-kidney (SPK) recipients have been extremely high (50-80%), with many second and third rejection episodes despite the use of quadruple immunosuppression (antibody induction and cyclosporine [CsA]-azathioprine [AZA]-based maintenance immunosuppression). Although this acute rejection has rarely led to graft loss, it has been a great cause of morbidity and of significantly increased cost. In an attempt to decrease the acute rejection rate and related morbidity in SPK transplant recipients, we compared two "state-of-the-art" immunosuppression regimens in a prospective, randomized, single-center study. METHODS: Patients who received SPK transplants were randomized to receive either tacrolimus (TAC) and mycophenolate mofetil (MMF, n=18) or CsA (Neoral formulation) and MMF (n=18). All patients received OKT3 induction and prednisone, which was tapered to 5 mg/day by 6 months after transplantation. All rejection episodes were biopsy proven. In addition, metabolic control (HgbA1C, hypertension, serum cholesterol), drug toxicity, and infection also were measured. Data were compared with that of a historical group (n=18) who received conventional CsA (Sandimmune formulation) and AZA-based immunosuppression. RESULTS: The incidence of biopsy-proven acute rejection was 11% in both the TAC-MMF and CsA-MMF groups with only two patients in each group experiencing a rejection episode. This rejection rate was significantly decreased from that of the CsA-AZA historical group (77%, P<0.01). There were no significant differences in infection rates, including cytomegalovirus, or in metabolic control (HgbA1C, hypertension, and cholesterol levels). All patients remained on their initial immunosuppression regimen for the first 3 months after transplantation. Between 3 and 6 months after transplantation, three patients were switched from TAC to CsA for recurrent migraine headaches, posttransplant diabetes, and chronic cytomegalovirus infection. Two patients in the CsA-MMF group died of nonimmunologic causes (aspiration pneumonia and arrhythmia) between 3 and 6 months after transplantation. CONCLUSIONS: The data from this study show that MMF treatment significantly decreases the incidence of biopsy-proven acute rejection in SPK transplant recipients compared with AZA-treated historical controls. In addition, we conclude that TAC and CsA (Neoral), when combined with MMF, yield similar, low acute rejection rates with similar graft function and metabolic control.

Adult↗
PubMed1997

Impact of HIV infection on the development, clinical presentation, and outcome of tuberculosis among children in Abidjan, Côte d'Ivoire.

OBJECTIVE: To assess the impact of HIV infection upon the development, clinical presentation, and outcome of tuberculosis (TB) among children. DESIGN: Case-control study and prospective cohort study. METHODS: From March 1994 to November 1995, children aged 0-9 years with newly diagnosed TB were enrolled at the two outpatient TB centers and the two principal university hospitals in Abidjan, Côte d'Ivoire. Children were examined, blood samples were collected for HIV serology and lymphocyte phenotyping, chest radiography was performed, and gastric aspirates and sputum samples were collected for acid-fast bacilli smear and culture. Children were then followed every 2 months during a standard 6-month course of anti-TB therapy. To examine risk factors for TB, age- and sex-matched healthy control children were enrolled from among the siblings of children referred for TB skin testing. RESULTS: Overall, 161 children with TB were enrolled, including 39 (24%) with culture-confirmed pulmonary TB, 80 (50%) with clinically diagnosed pulmonary TB, and 42 (26%) with extrapulmonary TB. Children with TB were significantly more likely than 161 control children to be HIV-seropositive (19 versus 0%), to have a past TB contact (55 versus 16%) and to live in very low socioeconomic status housing (24 versus 6%). No significant differences between HIV-seropositive and seronegative children were found in the distribution of radiologic abnormalities for pulmonary TB or in the site of extrapulmonary TB. The mortality rate in HIV-seropositive children was significantly higher than in seronegative children (23 versus 4%; relative risk, 3.6; 95% confidence interval, 2.0-6.6), and all deaths in HIV-seropositive children with available lymphocyte subtyping results occurred in those with a CD4 percentage of < 10%. CONCLUSIONS: This study documents the importance of HIV infection as an independent risk factor for the development of TB in children, and demonstrates that HIV-related immunosuppression is a critical risk factor for mortality in this population.

AIDS-Related Opportunistic Infections↗
PubMed1995

EC/US workshop report: assessment of genetic risks associated with exposure to ethylene oxide, acrylamide, 1,3-butadiene and cyclophosphamide.

The EC/US Workshop on Risk Assessment: 'Human Genetic Risks from Exposure to Chemicals, Focusing on the Feasibility of a Parallelogram Approach' had as its main objective the identification of the methodology, data requirements and mechanistic research to understand the human health impact of germ cell mutagens. Specifically, it represented an evaluation of current knowledge and the identification of future research needs for a more precise assessment of human genetic risks from exposure to mutagenic chemicals. Four chemicals were selected for review at the Workshop and in this Special Issue: ethylene oxide, 1,3-butadiene, acrylamide, and cyclophosphamide. The first three are important industrial chemicals with substantial use worldwide and, therefore, considerable potential for human exposure. The fourth, cyclophosphamide, is a commonly used cancer chemotherapeutic agent. This Special Issue contains the major scientific reports from the workshop. These include four Introductory Papers (on the parallelogram concept, alternative genetic risk assessment approaches, regulatory data needs, and the research background for risk assessment of ethylene oxide), four Working Group Reports on the specific compounds mentioned above and, finally, three Crosscutting Papers pertinent to the issue of germ-line mutagenesis and genetic risk estimation.

Acrylamide↗
PubMed1995

The effects of oophorectomy and female sex steroids on glucose kinetics in the rat.

In order to clarify the roles played by female sex steroids on glucose metabolism, basal glucose kinetics were studied in control sham operated (C), oophorectomised (O), 17-beta-oestradiol treated oophorectomised (1.5 micrograms/day) (E) and progesterone treated oophorectomised (1.5 mg/day) (P) female rats. Hormone (or vehicle only) delivery was via osmotic pumps which were inserted at the time of oophorectomy (or sham operation) 7 days prior to metabolic testing. In fasted anaesthetised rats, hepatic glucose production (HGP), plasma glucose metabolic clearance rate (MCR) and glucose uptake indices (GUI) of selected peripheral tissues were measured using radioactive tracer methodology. Following surgery, the O rats significantly gained and the E rats significantly lost weight compared to the C rats. Plasma insulin and glucose were not different between groups. HGP and MCR were increased by 24-29% (P < 0.005) and 19-28% (P < 0.001), respectively, in the O compared to the C, E and P rats. The GUI of brown adipose tissue was significantly reduced in the P compared to the C rats (3 +/- 1 vs 25 +/- 10 micromol/100 g/min). In conclusion, female sex steroid hormones significantly influence rat body weight, hepatic glucose metabolism and the metabolism of brown adipose tissue.

Animals↗
PubMed1995

The role of the renin-angiotensin system in cisplatin nephrotoxicity.

The role of the renin-angiotensin system (RAS) in the pathogenesis of cisplatin nephrotoxicity was evaluated in an experimental rat model using a specific, nonpeptide angiotensin II(AII) receptor blocker, losartan. Rats were treated with a single dose of losartan (at 10 mg/kg and 30 mg/kg, i.p.) or saline, 2 h prior to cisplatin administration (5 mg/kg, i.p.). Renal function was assessed 3 and 7 days after cisplatin treatment. A second group of rats received losartan (10 mg/kg, i.p.) or saline, 2 h prior to cisplatin administration (5 mg/kg, i.p.), and losartan (10 mg/kg, i.p.) or saline daily for 6 days after cisplatin treatment. Renal function was assessed on day 7. Neither high- nor low-dose losartan pretreatment prevented development of cisplatin-induced nephrotoxicity. Blood urea nitrogen (BUN) and plasma creatinine values at 7 days were similar to those of animals receiving cisplatin alone (BUN: 17.12 +/- 1.1 and 22.17 +/- 2.2 vs. 20.58 +/- 2.4 mg/dL; creatinine: 1.04 +/- 0.05 and 0.82 +/- 0.09 vs. 0.84 +/- 0.06 mg/dL). A significant reduction in creatinine clearance with cisplatin treatment was seen 3 days after therapy, which was not prevented by pretreatment with losartan (GFR in controls: 2.1 +/- 0.16 mL/min; cisplatin: 0.24 +/- 0.05; cisplatin plus low-dose losartan: 0.05 +/- 0.03 and cisplatin plus high-dose losartan: 0.37 +/- 0.05). All groups of cisplatin-treated rats displayed systemic signs of cisplatin toxicity: reduced food intake and body weight. Rats receiving chronic losartan treatment had more rapid weight gain and lower BUN and plasma creatinine levels on day 7 than rats receiving cisplatin alone (BUN: 24.0 +/- 2.64 vs. 36.4 +/- 0.91 mg/dL; p < 0.05; plasma creatinine: 0.86 +/- 0.06 vs. 1.15 +/- 0.07 mg/dL; p < 0.05). Acute blockade of the AII receptor with losartan does not alter the onset or severity of cisplatin nephrotoxicity. Chronic blockade of the AII receptor may improve the rate of recovery of renal function in cisplatin-treated rats.

Angiotensin II↗