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Biomedical subjects

T O'Connor

Publications and source records attributed to T O'Connor.

At least 19 recordsLinked to original sources

Registered nurses' experiences with an evidence-based home care pathway for myocardial infarction clients.

OBJECTIVES: To obtain home health nurses' comments on an evidence-based care pathway for post myocardial infarction. DESIGN: A qualitative design was used. SETTING: Culturally diverse, lower income area of a large city. PARTICIPANTS: All home health nurses from one nursing agency who participated in a comparative study on the impact of the evidence-based care pathway. RESULTS: The largest number of comments made by the nurses were related to the beneficial impact of the pathway on the provision of quality nursing care and on increased job satisfaction. The home health nurses reported that the pathway increased clients' knowledge of medications and diet. In addition, they commented that they were able to use the pathway effectively because of the training they received from the inpatient cardiac nurses. CONCLUSIONS: This qualitative study demonstrates the benefits of investing in the implementation of best practice guidelines by home health nurses. However, nursing associations, such as the Canadian Community Health Nurses Initiatives Group, will need to continue to champion for additional funds to support the additional expenses incurred.

Aged↗

Hepatitis A vaccination--a prison-based solution for a community-based outbreak?

In December 2001, an increase in cases of hepatitis A was observed in South Yorkshire. Cases were predominantly young males who reported injecting drug use. A community-based vaccination programme was introduced in November 2002, but new cases continued to occur. In March 2003, a vaccination campaign was implemented in the local prison for a four-week period. One thousand two hundred and thirty-six (91%) prisoners were vaccinated. Two thirds (895/1,363) of the prisoners came from the area affected by the outbreak and 52% (465/895) reported injecting drugs. The median age of injectors was 25 years. Notifications of cases of hepatitis A from South Yorkshire ceased in August 2003. Although on this occasion the prison vaccination campaign was probably implemented too late to have had a significant impact on the local outbreak, a large number of young male injectors from the local area were successfully vaccinated. This suggests that a prison-based intervention offers a potentially effective way of immunising the IDU population and interrupting a community-based outbreak.

Adolescent↗

'Chemical condoms' for the prevention of HIV infection: evaluation of novel agents against SHIV(89.6PD) in vitro and in vivo.

BACKGROUND: Vaginal agents which are antiviral and/or inhibit the entry of HIV into the cell could prevent heterosexual transmission of HIV, and protect women who cannot negotiate condom use. METHODS: Four agents have been investigated for activity in vitro and in vivo against SHIV(89.6PD): two anionic polymers, dextrin-2-sulphate (D2S) and PRO 2000 (P2K), and two virucidal agents; a non-ionic detergent, nonoxynol-9 (N9) and a cyclic peptide ionophore, gramicidin-D (GD). All four agents were investigated in rhesus macaques, using an intra-vaginal challenge of two inoculations of 1 x 104 50% tissue culture infectious doses (TCID)50 of SHIV(89.6PD). RESULTS: D2S, P2K, GD and N9 all inhibited SHIV(89.6PD) in vitro. In vivo, three out of four control macaques were infected as judged by viral culture, seroconversion, DNA and RNA PCR; infection was confirmed in four out of eight macaques pre-treated with P2K, two out of four pre-treated with D2S, one out of four pre-treated with N9, two out of four pre-treated with GD and four out of four pre-treated with D2S + GD, a combination additive in vitro. INTERPRETATION: D2S and PRO-2000, novel inhibitors of HIV entry, showed evidence of protection in vivo, comparable to that seen with the virucide, N9. These data, together with the results of phase I and phase II studies in healthy women which have shown minimal toxicity, support plans for a phase III efficacy trial of chemically simple inhibitors of HIV entry with low toxicity, for the prevention of HIV infection in women.

Administration, Intravaginal↗

High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes.

Nrf2, which belongs to the basic leucine zipper (bZip) transcription factor family, has been implicated as a key molecule involved in antioxidant-responsive element (ARE)-mediated gene expression. In order to examine the role of Nrf2 in protection against xenobiotic toxicity, the sensitivity of nrf2 knockout mice to acetaminophen (N-acetyl-4-aminophenol (APAP)) was analyzed. The saturation of detoxification pathways after high levels of exposure to APAP is known to induce hepatotoxicity. Two factors important in its detoxification are UDP-glucuronosyltransferase (UDP-GT), an ARE-regulated phase-II drug-metabolizing enzyme, and glutathione (GSH), an antioxidant molecule whose synthesis depends on ARE-regulated gamma-glutamylcysteine synthetase (gammaGCS). Two- to 4-month-old male mice were orally administered a single dose of APAP at 0, 150, 300, or 600 mg/kg. Doses of 300 mg/kg APAP or greater caused death in the homozygous knockout mice only, and those that survived showed a greater severity in hepatic damage than the wild-type mice, as demonstrated by increased plasma alanine aminotransferase activity, decreased hepatic non-protein sulfhydryl (NPSH) content, and centrilobular hepatocellular necrosis. The high sensitivity of Nrf2-deficient mice was confirmed from observations made at 0, 2, 8, and 24 h after dosing with 300 mg/kg APAP; increased anti-APAP immunoreactivity was also noted in their livers at 2 h. Untreated homozygous knockout mice showed both a lower UDP-GT activity and NPSH content, which corresponded to decreased mRNA levels of UDP-GT (Ugt1a6) and the heavy chain of gammaGCS, respectively. These results show that Nrf2 plays a protective role against APAP hepatotoxicity by regulating both drug metabolizing enzymes and antioxidant genes through the ARE.

Acetaminophen↗

Microsatellite instability and the clinicopathological features of sporadic colorectal cancer.

BACKGROUND AND AIMS: In this study, we prospectively examined the clinical significance of the microsatellite instability (MSI) phenotype in sporadic colorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice. METHODS: DNA was extracted from 310 tumours collected from 302 consecutive individuals undergoing curative surgery for sporadic colorectal cancer. Microsatellite status was determined by polymerase chain reaction amplification using standard markers, while immunostaining was used to examine expression of MLH1, MSH2, and p53. RESULTS: Eleven per cent of tumours showed high level instability (MSI-H), 6.8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological grade, have a mucinous phenotype, and to harbour increased numbers of intraepithelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) tumours showed loss of staining for MLH1 and a further three tumours showed absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%. CONCLUSIONS: We conclude that the MSI-H phenotype constitutes a pathologically and clinically distinct subtype of sporadic colorectal cancer. Immunohistochemical staining for MLH1 and MSH2 represents an inexpensive and accurate means of identifying such tumours.

Adult↗