PubMed Health⌕ Search

Biomedical subjects

M O'Leary

Publications and source records attributed to M O'Leary.

At least 19 recordsLinked to original sources
PubMed2006

A phase I clinical and pharmacokinetic study of the multi-drug resistance protein-1 (MRP-1) inhibitor sulindac, in combination with epirubicin in patients with advanced cancer.

PURPOSE: Multi-drug resistance mediated by ATP-binding cassette trans-membrane protein pumps is an important cause of cancer treatment failure. Sulindac has been shown to be a competitive substrate for the clinically important resistance protein, multi-drug resistance protein-1 (MRP-1), and thus might enhance the anti-cancer activity of substrate chemotherapeutic agents, e.g. anthracyclines. METHODS: We conducted a dose-escalating, single arm, prospective, open label, non-randomised phase I trial of epirubicin (75 mg/m(2)) in combination with escalating oral doses of sulindac (0-800 mg) in patients with advanced cancer to identify an appropriate dose of sulindac to use in future resistance studies. Anthracycline and sulindac pharmacokinetics were studied in cycles 1 and 3. RESULTS: Seventeen patients (8 breast, 3 lung, 2 bowel, 1 melanoma, 1 renal, 1 ovarian and 1 of unknown primary origin, 16/17 having had prior chemotherapy) were enrolled. Eight patients received a full six cycles of treatment; 14 patients received three or more cycles. Dose-limiting toxicity was observed in two patients at 800 mg sulindac (1 renal impairment, 1 fatal haemoptysis in a patient with advanced lung cancer), and sulindac 600 mg was deemed to be the maximum tolerated dose. Sulindac had no effect on epirubicin pharmacokinetics. Among 15 patients with evaluable tumour, two partial responses were seen (malignant melanoma and breast cancer). Four others had prolonged stable disease. CONCLUSION: Epirubicin 75 mg/m(2) and sulindac 600 mg are the recommended doses for phase II studies for these agents in combination.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Cervical screening history in patients with early stage carcinoma of the cervix.

This study aimed to examine whether a decade of heightened publicity on issues relating to cervical screening has changed the screening profile of women presenting with cervical cancer at the National Maternity Hospital. The screening history of 100 women diagnosed with early/surgically treated cervical cancer between 1998 and 2002 was compared with a similar study conducted in 1982 /1990. The percentage of women never screened was similar - 24 %( 2002) and 23% (1990). The interval between last recorded smear and diagnosis of disease was greater than 5 years in 45.6% and 41.7% respectively. Overall 60% of women in the recent period had either failed to avail of screening or were not screened within 5 years of diagnosis compared with 64% in 1990. Multiparous women comprised 90% of the study group and 50% of those inadequately screened were attending their general practitioner on a regular basis - therefore affording a potential for opportunistic screening The current method of screening has failed in this group and has not improved in 10 years despite of increased population awareness and greater opportunities for screening than ever before and would support an argument for a National Screening Program.

Adenocarcinoma↗
PubMed2005

Haemolytic uraemic syndrome associated with interfamilial spread of E. coli O26:H11.

In September 2000, haemolytic uraemic syndrome (HUS) was diagnosed in a 10-month-old child with a prodromal history of vomiting and diarrhoea (non-bloody). Investigation revealed that a self-limiting gastrointestinal illness (mean duration 48 h) had occurred among immediate and extended family in the 2 weeks prior to the child's admission. The epidemiology of the illness suggested person-to-person spread. Five children (close family contacts) had E. coli O26 verocytotoxin (VT1 and VT2) isolated from stools. Stool culture and serology from the index case were negative for shiga toxin-producing E. coli (STEC) organisms. Control measures in accordance with the Public Health Laboratory Service (PHLS), verocytotoxogenic organisms (VTEC) guidelines were applied to prevent further spread among the extended family and contacts. Despite detailed food and environmental exposure histories, the source of the illness was not identified. This incident highlights the importance of investigation of cases of post-diarrhoeal HUS, for potential shiga toxin E. coli aetiology.

Diarrhea↗
PubMed2005

Risk factors for disease progression in patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH): a systematic analysis of expert opinion.

Disease progression has become an important issue for the management of lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). Although several risk factors have been identified, no specific patient risk profiles have been established that can be useful in the day-to-day management of LUTS/BPH. In this study, an international panel of urologists developed a risk classification based on the attribution of a risk score to 243 unique patient profiles. From the perspective of clinical decision making, it was concluded that postvoid residual, symptom severity and maximum flow rate are the most relevant determinants of the risk of disease progression.

Disease Progression↗
PubMed2005

Integrating risk profiles for disease progression in the treatment choice for patients with lower urinary tract symptoms/benign prostatic hyperplasia: a combined analysis of external evidence and clinical expertise.

The RAND appropriateness method was used to explore the relevance of risk factors for disease progression in the treatment choice for patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). A total of, 12 international experts assessed the appropriateness of various treatments for 243 risk profiles. Highest appropriateness rates were found for alpha1-adrenoceptor antagonists (68% of profiles) and combination therapy (46%). A large prostate volume was the dominant argument in favour of 5alpha-reductase inhibitors and combination therapy, but was irrelevant for the choice of surgery. Considerable postvoid residual, severe symptoms and poor maximum flow rate were the most important factors in favour of surgery.

Disease Progression↗
PubMed2004

The North Dublin randomized controlled trial of structured diabetes shared care.

BACKGROUND: A new diabetes shared care service was introduced in North Dublin. It was designed as a randomized controlled trial with a complex intervention comprising education of participating practitioners, the introduction of a community-based diabetes nurse specialist, local agreement on clinical protocols and structured communication across the primary-secondary care interface. OBJECTIVES: Our aim was to assess the feasibility and effectiveness of a structured diabetes shared care service in a mixed health care system and to analyse the impact on total patient care. METHODS: A Cluster randomized controlled trial lasting 18 months was carried out in 183 patients with type 2 diabetes from 30 general practices in North Dublin. Biophysical outcomes (HbA1c, blood pressure, body mass index), psychosocial measures (smoking status and Diabetes Clinic Treatment Satisfaction and Diabetes Well-being scores) and process outcomes were collected. RESULTS: There were significant improvements in diabetes care delivery and in psychosocial outcomes, but no significant improvements in biomedical outcomes. Process data collection revealed a significant increase in diabetes care-related activity for participating patients with an increase in structured annual reviews and fewer patients defaulting from care. There were also significant improvements in information exchange between primary and secondary care. CONCLUSION: Structured diabetes shared care, in a mixed health care system, can produce significant improvements in diabetes care delivery and in psychosocial outcomes for patients, with improved information exchange across the primary-secondary care interface.

Adult↗
PubMed2004

Prevalence of sexually transmitted diseases and human immunodeficiency virus among women attending prenatal services in Apia, Samoa.

There is no routine prenatal screening for sexually transmitted diseases (STDs) and human immunodeficiency virus (HIV) in pregnancy in Samoa. Testing for chlamydial infection is not available. To gather information on pregnant women, a prevalence survey was conducted in Apia, Samoa, utilizing two prenatal hospital clinics. Pregnant (n=427) women were tested for Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis using polymerase chain reaction (PCR), and for syphilis (n=441) by rapid plasmid reagin (RPR) and HIV (n=441) by enzyme-linked immunosorbent assay (ELISA). Results were: chlamydia 30.9% (132); trichomoniasis 20.8%; gonorrhoea 3.3%; syphilis 0.5%; and HIV 0%. Overall 42.7% had at least 1 STD. Young women aged <25 years were three times more likely to have a STD than older women (odds ratio=3.0, 95% confidence intervals 2.0, 4.5). The lack of inexpensive, reliable field diagnostics remain a barrier to sustainable STD control programmes for pregnant women living in developing countries.

Adolescent↗
PubMed2004

Folic acid supplements to prevent neural tube defects: trends in East of Ireland 1996-2002.

Promotion of folic acid to prevent neural Tube Defects (NTD) has been ongoing for ten years in Ireland, without a concomitant reduction in the total birth prevalence of NTD. The effectiveness of folic acid promotion as the sole means of primary prevention of NTD is therefore questionable. We examined trends in folic acid knowledge and peri-conceptional use from 1996-2002 with the aim of assessing the value of this approach. From 1996-2002, 300 women attending ante-natal clinics in Dublin hospitals annually were surveyed regarding their knowledge and use of folic acid. During the period the proportion who had heard of folic acid rose from 54% to 94% between 1996 and 2002 (c2 test for trend: p<0.001). Knowledge that folic acid can prevent NTD also rose from 21% to 66% (c2 test for trend: p<0.001). Although the proportion who took folic acid during pregnancy increased from 14% to 83% from 1996 to 2002 (c2 test for trend: p<0.001), peri-conceptional intake did not rise above 24% in any year. There is a high awareness of folic acid and its relation to NTD, which is not matched by peri-conceptional uptake. The main barrier to peri-conceptional uptake is the lack of pregnancy planning. To date promotional campaigns appear to have been ineffective in reducing the prevalence of NTD in Ireland. Consequently, fortification of staple foodstuffs is the only practical and reliable means of primary prevention of NTD.

Adult↗
PubMed2003

A qualitative investigation of the views and health beliefs of patients with Type 2 diabetes following the introduction of a diabetes shared care service.

AIMS: A qualitative research approach was adopted in order to explore the views and health beliefs of patients with Type 2 diabetes who had experienced a new structured diabetes shared care service. METHODS: Patients from 15 general practices were randomly selected and invited to attend three focus groups. Two independent researchers adopted the "Framework" technique to analyse the transcribed data and identify key themes expressed by patients. RESULTS: Themes relating to diabetes included frustration, victimization and powerlessness in relation to living with diabetes, controlling blood sugar, medication and economic barriers to care. Differences in emphases between patients and healthcare providers emerged. Patients were generally positive about shared care and largely identified it with the nurses involved. CONCLUSION: This research highlights the importance of an in-depth exploration of patients' views during changes in diabetes care delivery to identify service delivery failures and gaps in patient knowledge such as lack of awareness of the extent of macrovascular risk.

Adaptation, Psychological↗
PubMed2003

Does neostigmine increase gastric emptying in the critically ill?--results of a pilot study.

OBJECTIVE: Based on the successful use of neostigmine for the treatment of acute colonic pseudo-obstruction, we hypothesised that neostigmine would increase gastric emptying and improve tolerance to enteral feeding in the critically ill patient. METHODS: Eleven patients intolerant of enteral feeds due to high gastric aspirates, were randomised to receive a 'study infusion' consisting of either neostigmine (0.4 mg/hr) or 0.9% saline. If, after 12 hours the patient was deemed intolerant of the nasogastric feed, the rate of the 'study infusion' was doubled. Those who remained intolerant after 24 hours of the 'study infusion' were 'crossed-over' and continued on the other infusion for a further 24 hours. Gastric emptying was assessed in each group before and after the infusion by measuring the hourly rates of feed "absorption" [(delivery rate + returned aspirates) - total aspirates] and paracetamol absorption using the area under a time-concentration curve at 120 minutes (AUC120). Differences within and between groups were analysed using Students t test and one-way analysis of variance. RESULTS: Six patients received neostigmine first and 5 received the placebo first. Four of the 6 patients receiving the neostigmine first compared with all of those receiving placebo first required to be 'crossed-over' to the other infusion. While the hourly rates of feed "absorption" were greater for patients receiving neostigmine than for placebo, these differences did not achieve statistical significance. The mean paracetamol AUC120 for all patients who received neostigmine was 3996 mg/min/L while that for placebo was 1929 mg/min/L (p = 0.21). CONCLUSIONS: These data suggest that while neostigmine may have a positive effect on gastric emptying and enteral feed absorption in critically ill patients, the results did not reach statistical significance and an adequately powered study will be required to confirm this effect.

Journal Article↗
PubMed2002

Botulinum toxin urethral sphincter injection resolves urinary retention after pubovaginal sling operation.

The management of prolonged urinary retention following pubovaginal sling surgery typically involves transvaginal urethrolysis for anatomical urethral obstruction. Brubaker recently reported on urethral sphincter abnormalities as a cause of postoperative urinary retention following either Burch suspension or a pubovaginal sling procedure. We report a case of functional urethral obstruction and detrusor acontractility following pubovaginal sling surgery that was successfully treated by botulinum A toxin urethral sphincter injection.

Aged↗
PubMed2002

Botulinum toxin urethral sphincter injection resolves urinary retention after pubovaginal sling operation.

The management of prolonged urinary retention following pubovaginal sling surgery typically involves transvaginal urethrolysis for anatomical urethral obstruction. Brubaker [1] recently reported on urethral sphincter abnormalities as a cause of postoperative urinary retention following either Burch suspension or pubovaginal sling procedure. We report a case of functional urethral obstruction and detrusor acontractility following pubovaginal sling surgery that was successfully treated by botulinum A toxin urethral sphincter injection.

Aged↗
PubMed2002

Cytogenetic and molecular heterogeneity of 7q36/12p13 rearrangements in childhood AML.

The t(7;12)(q36;p13) is a recurrent abnormality in acute myeloid leukemia (AML) of childhood. The involved gene on chromosome 12 is TEL; the 7q36 partner gene has not been identified. We describe morphologic, molecular and cytogenetic characterization of two cases of 7q36/12p13-associated AML that provide important insights regarding the consequences of this rearrangement. First, the molecular organization of the breakpoint regions differ significantly: one case is a reciprocal 7;12 translocation (RTR); the other has an insertion of 7q into 12p (INS). While 12p13 breakpoints in both patients interrupt TEL intron 1, the centromere to telomere orientation of the 7q36 sequences relative to the TEL sequences are inverted in INS compared to RTR. This difference makes it difficult to postulate a mechanism whereby both patients could produce a common fusion transcript. Further, no evidence was obtained for any TEL-containing fusion transcripts. Finally, we report the first cloning of a 7;12 genomic breakpoint (from RTR) and find that it maps to a site 30 kbp proximal to the HLXB9 gene in 7q36. Together, these data suggest that, unlike most leukemia-associated chromosomal rearrangements, the important consequence of the t(7;12) is likely not the generation of a novel fusion transcript, but instead the inactivation of TEL and/or a gene at 7q36.

Base Sequence↗