Biomedical subjects

A O'Neill

Publications and source records attributed to A O'Neill.

At least 19 recordsLinked to original sources

PubMed1998

No linkage or linkage disequilibrium between brain-derived neurotrophic factor (BDNF) dinucleotide repeat polymorphism and schizophrenia in Irish families.

There is increasing evidence that a neurodevelopmental process is accountable for at least a proportion of schizophrenic cases. Brain-derived neurotrophic factor (BDNF), a member of a group of proteins that includes neurotrophin-3/4/5 and nerve growth factor (NGF), is an attractive candidate gene. We have performed a case control association study using the BDNF dinucleotide repeat polymorphism in a sample of familial schizophrenic individuals and in healthy, ethnically matched control subjects. We also performed a linkage analysis on 265 multiplex families using the same marker. We found no differences in allele frequencies between the patient and control groups nor any evidence for transmission disequilibrium or linkage with the multiply affected families. We conclude that DNA variation at or near the BDNF gene is unlikely to contribute to the genetic predisposition to schizophrenia.

Alleles↗

PubMed1998

Screening patients in general practice with COPD for long-term domiciliary oxygen requirement using pulse oximetry.

Epidemiological data suggest long-term oxygen therapy (LTOT) delivered by oxygen concentrators in patients with severe hypoxic chronic obstructive pulmonary disease (COPD) is under-prescribed by General Practitioners (GPs) in England and Wales. One reason for this may be the unavailability to GPs of a measure of arterial oxygenation needed to fulfil the defined prescription criteria. Provision of a non-invasive measure of oxygenation may improve detection of hypoxic subjects and increase appropriate prescribing. This study aimed to evaluate pulse oximetry in a general practice setting and to screen for severe undetected hypoxaemia fulfilling the LTOT prescription criteria in patients with COPD. All COPD patients attending surgery in two practices were screened with oximeters for hypoxaemia. Those with an oxygen saturation of < or = 92% were referred to hospital for formal arterial blood gas analysis and an oxygen concentrator assessment. GPs were asked to evaluate their experience in the ease of use and application of oximetry. The number of patients receiving oxygen by concentrator before the study was compared with the national rate and the number after the study with the estimated need suggested by epidemiological studies. Over a 12-month period a total of 114 patients were screened in the two practices with a combined list size of 15,742. Thirteen patients had saturations of < or = 92%. Two refused and 11 underwent formal arterial gas analysis. Three had PaO2 < 7.3 kPa and new prescriptions for oxygen concentrators were made in these previously unsuspected severely hypoxaemic subjects as a result. One other hypoxaemic subject was referred and found to have another treatable medical condition. The initial prevalence of concentrator prescription (0.013% CI 0.003, 0.047) was similar to the national rate (0.024%) and the prevalence observed after screening (0.031%, CI 0.013, 0.073) fell within the lower suggested prescription need of previous epidemiological data (0.02-0.10%). All practitioners found the oximeters simple to use and helpful in assisting with assessment of the severity of their patient's condition. Oximetry provides a readily usable non-invasive method of screening and when applied to all COPD patients seen in general practice can reveal those fulfilling the criteria for long term oxygen who would otherwise not be identified as needing this treatment.

Aged↗

PubMed1998

Prognostic impact of amenorrhoea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: results of the International Breast Cancer Study Group (IBCSG) Trial VI.

Adjuvant chemotherapy-induced amenorrhoea has been shown to be associated with reduced relapses and improved survival for premenopausal breast cancer patients. Amenorrhoea was, therefore, studied to define features of chemotherapy (i.e. duration and timing) and disease-related factors which are associated with its treatment effects. We reviewed data from IBCSG Trial VI, in which accrual was between July 1986 and April 1993. 1196 of the 1475 eligible patients (81%) were evaluable for this analysis. The median follow-up was 60 months. Women who experienced amenorrhoea had a significantly better disease-free survival (DFS) than those who did not (P = 0.0004), although the magnitude of the effect was reduced when adjusted for other prognostic factors (P = 0.09). The largest treatment effect associated with amenorrhoea was seen in patients assigned to receive only three initial CMF courses (5-yr DFS: 67% versus 49%, no amenorrhoea; hazard ratio, 0.55; 95% confidence interval, 0.38 to 0.81; P = 0.002). DFS differences between amenorrhoea categories were larger for patients with ER/PR positive tumours (hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80; P = 0.0001). Furthermore, patients whose menses returned after brief amenorrhoea had a DFS similar to those whose menses ceased and did not recover (hazard ratio, 1.10; 95% confidence interval, 0.75 to 1.62; P = 0.63). The effects associated with a permanent or temporary chemotherapy-induced amenorrhoea are especially significant for node-positive breast cancer patients who receive a suboptimal duration of CMF chemotherapy. Cessation of menses, even for a limited time period after diagnosis of breast cancer, might be beneficial and should be prospectively investigated, especially in patients with oestrogen receptor-positive primaries.

Adult↗

PubMed1998

Examination of new and reported data of the DRD3/MscI polymorphism: no support for the proposed association with schizophrenia.

The dopamine D3 (DRD3) receptor gene has been implicated in the aetiology of schizophrenia as a candidate gene since it combines both the dopamine receptor and limbic hypotheses of the disease. Previous association studies of a DRD3/MscI polymorphism suggested an increased frequency of homozygosity at the DRD3 receptor gene in schizophrenia. Homozygosity appeared to be particularly frequent in male patients, individuals with family history of the disease and in good responders to neuroleptic treatment. Many studies have since examined this polymorphism and have altered or extended the original homozygosity hypothesis. In this study, we have investigated the distribution of the DRD3/MscI polymorphism in 198 Irish schizophrenic patients and 235 ethnically matched controls. Patients and controls showed-similar allele and genotype frequencies. Furthermore, linkage analysis using two microsatellite markers flanking the DRD3 gene was performed on 265 Irish schizophrenic families, with substantially negative results. Our findings, in combination with a review of previous studies do not support a role for the DRD3/MscI polymorphism in the pathogenesis of schizophrenia.

Alleles↗

PubMed1998

The vitronectin receptor associates with clathrin-coated membrane domains via the cytoplasmic domain of its beta5 subunit.

Rat myotubes cultured in fetal calf serum adhere to vitronectin-coated substrates through two distinct structures, focal contacts and clathrin-coated membrane domains. We studied the integrins in myotubes to learn how they associate with these two domains. Double label immunofluorescence studies with antibodies specific for clathrin, vinculin and several forms of integrin showed that focal contacts and clathrin-coated membrane domains contain both vitronectin receptors (VnR, containing beta-3 and beta-5integrins) and fibronectin receptors (FnR, containing beta1-integrin). VnR but not FnR associates tightly with the substrate in both domains, as the VnR alone remains attached to the coverslip when the lipid bilayer and other membrane proteins are removed by detergent. Ultrastructural studies confirmed the localization of the beta5 subunit of the VnR at both domains. We used intracellular injection and affinity chromatography to test the possibility that clathrin at coated membrane domains associates with the cytoplasmic sequence of the beta5 subunit of the VnR. Injection of a synthetic peptide containing the NPXY motif from the cytoplasmic domain of the human beta5 subunit, SRARYEMASNPLYRKPIST, depleted clathrin from coated membrane domains without affecting clathrin in perinuclear structures or vinculin at focal contacts. Injection of the homologous beta1 peptide, MNAKWDTGENPIYKSAVITT, also containing an NPXY motif, had no significant effect on any of these structures. Affinity matrices containing the beta5 but not the beta1 peptide selectively retained clathrin from myotube extract, and bound clathrin could be selectively eluted by soluble forms of the beta5 but not the beta1 peptide. Thus, a sequence including the NPXY motif in the integrin beta5 subunit is involved in the specific anchoring of the VnR, but not the FnR, to clathrin-coated membrane.

Amino Acid Sequence↗

PubMed1997

No association or linkage between the 5-HT2a/T102C polymorphism and schizophrenia in Irish families.

Recent findings of an association between schizophrenia and a T102C polymorphism at the 5-HT2a receptor gene (particularly with genotype 1-2 and 2-2 and allele 2) prompted us to investigate this marker in familial Irish schizophrenic patients, their relatives, and ethnically matched unrelated controls; 247 probands and 249 controls were included in this study. In contrast to some studies, we found no evidence of significant differences either in the frequency of the genotypes 1-2 and 2-2 or allele 2 between the schizophrenic patients and the controls. A transmission disequilibrium test, run on the full set of 265 families yielded no evidence to support linkage disequilibrium. Linkage analysis with both parametric and non-parametric methods yielded strongly negative results. Our findings are consistent with other recent association studies which argue against the involvement of the 5-HT2a/T102C polymorphism in predisposition to schizophrenia. The positive findings reported to date might have occurred by chance or the apparent conflict may be due to genetic heterogeneity between samples.

Disease Susceptibility↗

PubMed1997

Pervasive occult gastrointestinal bleeding in an Alaska native population with prevalent iron deficiency. Role of Helicobacter pylori gastritis.

OBJECTIVE: To confirm prevalent iron deficiency among Yupik Eskimos living in Alaska and to explore the frequency of and potential lesions accounting for occult gastrointestinal bleeding. DESIGN: Descriptive survey. SETTING: Rural Arctic community. SUBJECTS: A total of 140 adult volunteers from 3 villages in the Yukon-Kuskokwim Delta region of western Alaska. MAIN OUTCOME MEASURES: Daily iron intake, hematologic and biochemical indexes of iron status, fecal hemoglobin levels, stool parasites, and endoscopic findings. RESULTS: While dietary iron intake by Yupiks was similar to that of a reference population, iron deficiency prevalence was increased 13-fold in Yupik men and 4-fold in Yupik women. Fecal hemoglobin levels were elevated in 90% of subjects contrasted with only 4% of a reference group; median levels were 5.9 and 0.5 mg of hemoglobin per gram of stool, respectively. Among 70 Yupik subjects with elevated fecal hemoglobin levels who had endoscopy performed, 68 (97%) had an abnormal gastric appearance consisting of erythema, mucosal thickening, diffuse mucosal hemorrhages, erosions, or ulcerations. Gastric biopsies revealed chronic active gastritis with associated Helicobacter pylori in 68 (99%) of 69. No other hemorrhagic gastrointestinal disease was detected. CONCLUSIONS: Based on this study sample, occult gastrointestinal bleeding appears to be pervasive in the Yupik population and likely underlies the prevalent iron deficiency. An atypical hemorrhagic gastritis associated with H pylori infection is present almost universally and may represent the bleeding source.

Adult↗

PubMed1997

Menstrual cycle and timing of breast surgery in premenopausal node-positive breast cancer: results of the International Breast Cancer Study Group (IBCSG) Trial VI.

PURPOSE: It has been postulated that breast cancer surgery performed during the follicular phase of the menstrual cycle is associated with poorer outcome. PATIENTS AND METHODS: We tested this hypothesis by evaluating disease-free survival (DFS) for 1033 premenopausal patients who received definitive surgery either during the follicular phase (n = 358) or the luteal phase (n = 675). All patients were enrolled in a randomized trial conducted between July 1986 and April 1993. All had node positive breast cancer and randomization was stratified by estrogen receptor (ER) status. All patients received at least three cycles of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months. RESULTS: Patients who underwent definitive surgery for breast cancer in the follicular phase had a slightly worse disease-free survival than those operated on during the luteal phase (five-year DFS percentage: 53% versus 58%; hazard ratio, 1.13; 95% confidence interval (CI), 0.94-1.38; P = 0.20). The effect was significantly greater for the subpopulation of 300 patients with ER-negative primaries (P = 0.02 interaction effect; five-year DFS percentages 42% vs. 59%; hazard ratio 1.60; 95% CI, 1.12-2.25; P = 0.008). The effect of timing of surgery diminished for analyses based on lesser surgical procedures, e.g., excisional biopsies. In particular, no effect of timing was observed for fine needle aspiration procedures. CONCLUSIONS: Surgical procedures which are more extensive than a fine needle aspiration biopsy might be associated with worse prognosis if conducted during the follicular phase of the menstrual cycle. This phenomenon was seen predominantly for high risk breast cancer with low levels or no estrogen receptors in the primary tumor.

Breast Neoplasms↗

PubMed1997

The cholesteryl ester transfer protein (CETP) locus as a candidate gene in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a relatively common disease of the elderly presenting as progressive dilatation of the abdominal aorta. The condition shows a pronounced tendency to cluster in families, indicating a genetic component in the disease aetiology. We have screened the cholesteryl ester transfer protein (CETP) gene, which has been proposed as a candidate gene in AAA, by means of SSCP, DNA sequencing and restriction analysis in a cohort of patients with AAA and a matching control group drawn from the Irish population. The analysis has demonstrated sequence variation at four sites in the CETP gene: an A-T transversion in exon 9 (producing a Lys309-Stop codon substitution), a G-A transition in exon 14 (producing a conservative Val421-Ile substitution), a C-T transition in intron 12 and a G-A transition in intron 15. None of the last three sites corresponded with sites of functional significance in the protein, suggesting that this reflects neutral polymorphism at the CETP locus. Furthermore, the frequencies of these four polymorphisms in the AAA patient and control groups were not significantly different. These data therefore suggest that CETP may be excluded as a candidate gene in abdominal aortic aneurysm.

Aortic Aneurysm, Abdominal↗

PubMed1997

Prediction of response to antiestrogen therapy in advanced breast cancer patients by pretreatment circulating levels of extracellular domain of the HER-2/c-neu protein.

PURPOSE: Overexpression of the HER-2/c-neu/c-erbB2 proto-oncogene is associated with a worse prognosis in patients with breast cancer, perhaps due to an association of the HER-2 proto-oncogene protein with resistance to hormone and/or chemotherapy. Circulating levels of the extracellular domain (ECD) of the HER-2/c-neu-related protein (NRP) are elevated in 20% to 40% of patients with metastatic breast cancer. We investigated whether pretreatment levels of NRP predict response to hormone therapy (HT). MATERIALS AND METHODS: Circulating NRP levels were determined in 94 patients who participated in a randomized trial of three different doses of the antiestrogen, droloxifene (DRO), as first-line HT for metastatic breast cancer. RESULTS: NRP levels were elevated (> or = 5,000 U/mL) in 32 of 94 patients (34%). Only three of 32 patients (9%) with elevated NRP levels responded to DRO, compared with 35 of 62 (56%) with nonelevated NRP levels (P = .00001). Low pretreatment NRP level was the most powerful predictor of response to DRO (odds ratio of response, 22.4; P = .0001). Elevated pretreatment NRP levels were also associated with a shorter time to progression (TTP) and survival duration. CONCLUSION: Pretreatment circulating NRP levels predict a low likelihood of benefit from HT, specifically DRO, in patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive or receptor-unknown metastatic breast cancer, even when adjusted for other known predictive factors, such as ER and/or PgR levels, site of disease, disease-free interval from primary treatment to recurrence, and prior adjuvant chemotherapy. These data suggest that pretreatment NRP levels may be useful in deciding whether to treat a patient who otherwise appears to be likely to respond to HT.

Aged↗

PubMed1997

Experiences with sedation and restraint during dental treatment in Romania.

In August, 1995 dental treatment was provided in an orphanage in Romania. This treatment took place over three weeks using three different dentists. Two dental nurses served for full the duration. For the last two weeks the team was joined by a dental health educator. All have given accounts of their time in Romania. The patients had various degrees of handicap but generally co-operation for treatment was poor. Most patients needed pre-operative sedation of oral valium. A papoose board was used for restraint. All the contributors agree that this was extremely helpful in controlling the patients. Dental treatment was mostly-restricted to extractions. A parallel preventive programme was run by the dental health educator. The team encountered bureaucratic problems which were overcome. All 220 children in the orphanage were screened and treated. Local children and adults were also given dental treatment when time allowed. The team wish to express gratitude to all who helped and supported them. They plan a future mission in 1997. In 1994, a dental team had previously travelled to Romania and carried out treatment of handicapped children using sedation & restraint. The principal difference between 1994 and 1995 was the introduction of the papoose board as the method of restraint. The papoose board is a temporary restraint device for use during medical or dental procedures. It is a set of canvas flaps with velcro fasteners on a board. A head strap and wrist straps are important accessories. Pre-operative sedation was given to the children 2-3 hours in advance of dental treatment. This usually was 10-20 mg oral valium. The child was then led into the dental surgery by hand and placed on the papoose board, which was already situated on the reclined dental chair. Before the child realised what was happening the wrist straps and leg straps were in place. Within seconds the other straps were closed and the child was totally restrained and ready for dental treatment. Dental treatment was then carried out using local anaesthesia. Care has to be taken that the restraint does not impair the patient's breathing, circulation, cause over-heating or positional injuries. A dental health education programme was run in parallel with the treatment service. The individual accounts of experiences follow. Firstly, the joint account of Dental Nurses Catherine Treacey and Karen Vaughan from the Dublin Dental Hospital, who were working for the full three weeks. Then follow the accounts of the dentists. On week 1 by Anne O'Neill, who works with the Eastern Health Board in the Dun Laoghaire area, week 2 by Robert Gorby, a dentist in private practice in Carlow, and week 3 by Brendan Fanning who works part-time for the Eastern Health Board, in Wicklow and part-time in practice in Ashford, Co. Wicklow. The final account is of the dental health education programme by Miriam Henshaw, Health Educator who works for the Eastern Health Board in the Wicklow area.

Adolescent↗

PubMed1997

A phase I trial of a new recombinant human beta-interferon (BG9015) for the treatment of patients with recurrent gliomas.

Primary brain tumors represent an important cause of cancer-related morbidity and mortality in the United States. Despite advances in neurosurgery and radiotherapy, the median survival of patients with malignant gliomas remains less than 1 year. A contributing factor to the poor prognoses of these patients is the diffuse, infiltrative nature of these tumors, which limits the effectiveness of focal therapies (i.e., surgery and radiation). Unfortunately, standard chemotherapy has been of limited benefit in the treatment of malignant gliomas, underlying the necessity for new drugs with novel mechanisms of action. On the basis of promising in vitro and clinical data demonstrating significant antiglioma activity of purified IFN-beta and a synthetic IFN-beta (Betaseron), we conducted a Phase I trial of a new, nonmutated, glycosylated recombinant human IFN-beta (BG9015) in patients with recurrent, high-grade astrocytomas. In this trial, we demonstrate that the maximally tolerated dose of BG9015 is 6 million units/m2 delivered by intramuscular injection three times per week. Dose-limiting neurotoxicity was seen in both patients treated at 8 million units/m2. Additionally, we demonstrate that high BG9015 serum levels are associated with a fall in natural killer cell number, radiographic response, and prolonged survival. We conclude that BG9015 has activity in patients with malignant gliomas, although the therapeutic index may be narrow. Future studies will be needed to confirm the observation that natural killer cell number and activity as well as BG9015 serum levels are important markers of antitumor activity.

Adult↗

PubMed1996

Health status response of rheumatoid arthritis to treatment with DAB486IL-2.

OBJECTIVE: To examine and compare health status and disease activity changes in patients with rheumatoid arthritis (RA) in a clinical trial of the biologic agent DAB486IL-2. METHODS: Data on 45 patients with RA who were enrolled in a multicourse, double-blind trial, consisting of a first, placebo-controlled, course followed by open-label treatment with the active agent to a total of 3 active courses, were examined for evidence of improvement in health status (measured using the 5 components of the Arthritis Impact Measurement Scales 2 [AIMS2]) and disease activity (measured using standard clinical measures and erythrocyte sedimentation rate). RESULTS: Over a single course of treatment, DAB486IL-2-treated patients showed significant improvement relative to placebo-treated patients on the symptom and social components of AIMS2 and in patient's assessment of disease activity. With subsequent open-label courses of treatment with DAB486IL-2, all 5 AIMS2 health status components and the disease activity measures of tender and swollen joint counts, grip strength, and the observer and patient assessments showed steady and generally parallel improvement. CONCLUSION: Short-term health status effects of this biologic agent were detected using the AIMS2.

Activities of Daily Living↗

PubMed1996

Objectively assessing nursing practices: a curricular development.

In preparation for the changing needs of undergraduate nursing students undertaking a Project 2000 degree, it was necessary to rethink the nursing skills programme. After studying the literature a nursing skills laboratory was designed which provided both an institutional and a domestic setting. A progressive programme was developed, to help the students learn nursing practices, which was based on the Objective Structured Clinical Evaluation (OSCE). A small pilot study was set up using second and third-year students from the traditional nursing studies degree. A number of stations were set up comprising various nursing scenarios. The students who were being assessed rotated through these. Other students acted as patients, examiners and some volunteered to be novices being taught by the more senior students. A set of marking criteria was drawn up for each station to enable each student to be assessed objectively. One of the stations was filmed to provide the students with personal feedback. By the end of the session the students had rotated through each of the stations and received the marked criteria as feedback. At the end of the session a focused group interview took place with all the students and the two lecturers involved in setting up the project. Students were positive and felt the process had potential for future development as a means of integration and consolidation of skills prior to clinical experience. The early introduction of filming to the programme was though to be of benefit by reducing stress levels through regular use. Students felt that the role of teaching the 'novice' helped them focus on their knowledge and performance. This process is resource intensive in human and non-human terms but enables small groups of students to learn in a realistic but safe, non-threatening environment and encourages them to take responsibility for their own learning.

Clinical Competence↗

PubMed1995

Apoptotic and mitotic indices in malignant melanoma and basal cell carcinoma.

AIMS: To assess the relative frequency of mitotic and apoptotic cells in malignant melanoma and basal cell carcinoma. METHODS: Retrospective evaluation of haematoxylin and eosin stained slides from 10 basal cell carcinomas, 10 nodular melanomas, and 10 superficial spreading melanomas, with counting of apoptotic and mitotic cells per 1000 cells. Selected cases were studied with in situ end-labelling. RESULTS: The ratio of apoptotic to mitotic cells was higher in basal cell carcinoma than in either form of melanoma because of the presence of a greater number of apoptotic cells in basal cell carcinoma. CONCLUSION: The differing growth rates and biological behaviour of these two tumours is reflected in the apoptotic:mitotic ratio. Further assessment of this ratio is warranted, both between tumour types and between individual tumours of one type, to determine its value as an indicator of biological potential.

Apoptosis↗

PubMed1994

Danger and safety in medicines.

Convictions about established medical safety and the danger of alternative remedies and practitioners are discussed in this article. While most alternative medicines continue to be denounced as unscientific and unsafe, government reviews have concluded that chiropractic and osteopathy and (more recently) acupuncture should be registered occupations and that qualifying courses of tertiary education should be instituted in Australia. This paradoxical result follows the widespread adoption of acupuncture and spinal manipulation by established practitioners of medicine and physiotherapy. The practices become intrinsically dangerous as their efficacy is accepted. Consequently, the argument is that only established practitioners are safe enough to use them. But alternative groups can use the established announcement of danger to represent the desirability of official action to protect the public. The article concludes with a review of the idea that therapies become dangerous as they are introduced.

Acupuncture Therapy↗

PubMed1994

Chiropractic and the politics of health care.

Musculoskeletal disorders remain a common disability suffered by Australians, but the question of who should treat them remains a contentious issue as the first centenary of the original chiropractic adjustment approaches. This paper, part of a longitudinal study of the role of chiropractic in the Australian health system, analyses this ongoing debate. Recent events are analysed here in this commentary on the politics of health care in this field. These include meta-analysis to evaluate the effectiveness of spinal manipulation for the treatment of lower back pain, recent legal action in the United States, and the recent epistle against Australian chiropractors published by the Australian Medical Association.

American Medical Association↗

PubMed1994

A national survey of asthma prevalence, severity, and treatment in Great Britain.

Parents of 5472 children aged 5-17 years from 3209 families were interviewed in a nationwide household survey. In the past year, 15.0% of children had wheezed, 2.2% had more than 12 attacks, and 2.3% had experienced a speech limiting attack. Altogether 4.3% were woken more than once a week by wheezing, 13.1% had doctor diagnosed asthma, and 13.6% had been prescribed antiasthmatic drugs in the past year. With increasing age, morbidity related to wheezing declined to a greater extent than annual period prevalence. The prevalence of wheeze varied little by socioeconomic group, but there were marked trends in all three indices of severity towards increased morbidity in poorer families. Diagnostic labelling and drug treatment of wheezy children did not differ substantially with socioeconomic status. Thus, a degree of socioeconomic equality exists in the process of medical care for childhood asthma in Britain. This does not appear to have resulted in equality of outcome.

Adolescent↗