Routine histological examination of the mastectomy scar at the time of breast reconstruction.
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Breast Neoplasms↗
Biomedical subjects
M O'Brien
Publications and source records attributed to M O'Brien.
Vinflunine -- an active chemotherapy for treatment of advanced non-small-cell lung cancer previously treated with a platinum-based regimen: results of a phase II study.
A multicentre, single-arm, phase II trial designed to determine the efficacy of single-agent vinflunine in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with a platinum-based regimen. The objectives were to assess efficacy in terms of tumour response rate (primary end point), duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients with advanced NSCLC with progressive disease having failed prior platinum-based first-line treatment for advanced disease. Five responses out of the 63 treated patients were documented by WHO criteria and validated by an independent panel review (IRP), yielding a response rate of 7.9% (95% CI: 2.6-17.6) in the intent-to-treat analysis and 8.3% (95% CI: 2.8-18.4) in the evaluable population. Disease control was achieved in 35 out of 60 evaluable patients (58.3%). The median duration of response (complete response+partial response), according to modified WHO criteria was 7.8 months (95% CI: 4.6-NR). Median PFS was 2.6 months (95% CI: 1.4-3.8), and the median survival was 7.0 months (95% CI: 5.8-9.2). Grades 3-4 neutropenia was reported in 50% of patients; febrile neutropenia was observed in two patients (3.2%); grades 3-4 myalgia and grade 3 constipation were experienced by 10 (15.9%) and six (9.5%) of patients, respectively. Constipation was manageable, non-cumulative and could be prevented with laxative prophylaxis. The encouraging results from this phase II study with vinflunine warrant further investigations in phase III trials as second- or first-line treatment of advanced non-small-cell lung carcinoma, as a single agent or in combination with other active drugs.
Adult↗
Reference models for mitral valve tissue engineering based on valve cell phenotype and extracellular matrix analysis.
The advance of mitral valve repair techniques through tissue engineering is impeded by the lack of information regarding the cellular and extracellular components of the mitral valve. The present study aims to expand our understanding of the mitral valve structure by analysing the synthesis of extracellular matrix (ECM) proteins and the expression of nitric oxide synthase (NOS). Valvular endothelial cells (VECs) and valvular interstitial cells (VICs) were isolated from porcine mitral valves. Immunochemical staining of ECM components, including type I, II, III, IV and V collagen, laminin, fibronectin, elastin and chondroitin sulphate (CS), was performed on both mitral valve tissue and cell cultures. Reverse transcription polymerase chain reaction and immunochemistry were used to analyse NOS expression in native valve and in culture. Both VECs and VICs synthesised the basement membrane components, laminin and type IV collagen both in vivo and in vitro, amongst other fibrous ECM proteins. Synthesis of type I collagen and CS was absent in VEC cultures. Each cell type had a characteristic profile of NOS expression. VECs synthesised endothelial NOS both in vivo and in vitro, with a minority of VICs expressing neuronal NOS in vitro. The present study reports newly recognised aspects of the mitral valve structure and the in vitro behaviour of mitral valve cell populations based on ECM synthesis and NOS expression. The presented profiles can be used as base tools for the generation of data necessary for the selection of ideal cell sources and for the design of appropriate scaffolds for the development of effective tissue-engineered mitral valves.
Actins↗
A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1).
BACKGROUND: Phase III studies suggest that non-small-cell lung cancer (NSCLC) patients treated with cisplatin-docetaxel may have higher response rates and better survival compared with other platinum-based regimens. We report the final results of a randomised phase III study of docetaxel and carboplatin versus MIC or MVP in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with biopsy proven stage III-IV NSCLC not suitable for curative surgery or radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75 mg/m(2), carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2) and cisplatin 50 mg/m(2) or mitomycin 6 mg/m(2), vinblastine 6 mg/m(2) and cisplatin 50 mg/m(2), respectively), 3 weekly. The primary end point was survival, secondary end points included response rates, toxicity and quality of life. RESULTS: The median follow-up was 17.4 months. Overall response rate was 32% for both arms (partial response = 31%, complete response = 1%); 32% of MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and 35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms. Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P = 0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and global health status whereas the DCb arm showed no significant change. CONCLUSIONS: The combination of DCb had similar efficacy to MIC/MVP but quality of life was better maintained.
Adult↗
Endoscopic band ligation of bleeding dieulafoy lesions: the best therapeutic strategy.
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Adolescent↗
What are children's trusts? Early findings from a national survey.
BACKGROUND: The Children Act 2004 and National Service Framework for Children, Young People and Maternity Services require fuller integration of health, education and social services for children and young people in England and Wales. The UK government supported the establishment of 35 experimental children's trust pathfinders (henceforth called children's trusts) in England. METHODS: A questionnaire was completed by managers in all 35 children's trusts a year after their start. Children's trust documents were examined. Census and performance indicators were compared between children's trust areas and the rest of England. RESULTS: Children's trust areas had demographic and social characteristics typical of England. All children's trusts aimed to improve health, education and social services by greater managerial and service integration. All had boards representing the three sectors; other agencies' representation varied. Two-thirds of children's trusts had moved towards pooling budgets in at least some service areas. At this stage in their development, some had prioritized joint procurement or provision of services, with formal managerial structures, while others favoured an informal strategic planning, co-ordination and information sharing approach. The commonest priorities for services development were for disabled children (16 children's trusts), followed by early intervention (11) and mental health services (8). CONCLUSIONS: The diverse strategies adopted by these 35 children's trusts during their first year is due to their own characteristics and to the way government strategy developed during this period. Whilst some prioritized organizational development, joint financing and commissioning, and information sharing, others laid more emphasis on mechanisms for bringing front-line professionals closer together. Their experiences are of value to others deciding how best to integrate children's services.
Adolescent↗
Prevalence of environmental Aeromonas in South East Queensland, Australia: a study of their interactions with human monolayer Caco-2 cells.
AIMS: To investigate the prevalence of Aeromonas in a major waterway in South East Queensland, Australia, and their interactions with a gut epithelial model using Caco-2 cells. METHODS AND RESULTS: A total of 81 Aeromonas isolates, collected from a major waterway in South East Queensland, Australia, were typed using a metabolic fingerprinting method, and tested for their adhesion to HEp-2 and Caco-2 cells and for cytotoxin production on Vero cells and Caco-2 cells. Aeromonas hydrophila had the highest (43%) and Aeromonas veronii biovar sobria had the lowest (25%) prevalence. Four patterns of adhesion were observed on both HEp-2 and Caco-2 cell lines. Representative isolates having different phenopathotypes (nine strains) together with two clinical isolates were tested for their translocation ability and for the presence of virulence genes associated with pathogenic Escherichia coli. The rate and degree of translocation across Caco-2 monolayers varied among strains and was more pronounced with LogA pattern. Translocation was associated with the adherence of strains to Caco-2 cells microvilli, followed by internalization into Caco-2 cells. Two Aer. veronii biovar sobria strains were positive for the presence of heat-labile toxin genes, with one strain also positive for Shiga-like toxin gene. CONCLUSIONS: Pathogenic strains of Aeromonas carrying one or more virulence characteristics are highly prevalent in the waterways studied and are capable of translocating across a human enterocyte cell model. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicates that Aeromonas strains carrying one or more virulence properties are prevalent in local waterways and are capable of translocating in a human enterocyte cell culture model. However, their importance in human gastrointestinal disease has yet to be verified under competitive conditions of the gut.
Aeromonas↗
Exploring the views of second-year Foundation Programme doctors and their educational supervisors during a deanery-wide pilot Foundation Programme.
AIM: To explore the views of second-year Foundation Programme doctors (F2s) and their educational supervisors taking part in a deanery-wide pilot Foundation Programme, in order to gain an understanding of their perceptions of the available learning experiences, support and supervision. METHODS: 20 semi-structured interviews were undertaken with randomly selected F2 doctors and educational supervisors participating in the deanery-wide pilot Foundation Programme. RESULTS: F2 trainees received appropriate and sufficient support and supervision from a variety of sources during their placements; however, it was believed that additional training of educational supervisors was required. Trainees reported some problems with the perception of the role of an F2; further understanding of the purpose and role of the F2 programme is required at trust level. The portfolio was viewed positively as a record and a learning tool, but was thought to be too bureaucratic. Trainees believed that it was more beneficial to their careers to take part in a foundation programme as opposed to a traditional senior house officer post, but both trainees and educational supervisors expressed some concerns about the generic nature of some skills F2s were expected to acquire. CONCLUSIONS: This evaluation has highlighted successful aspects of the Foundation Programme, particularly with regard to the level of support and range of experiences provided for trainees. Issues of concern to both trainees and educational supervisors have been identified, which require additional understanding.
Attitude of Health Personnel↗
Tolerance of high-dose (3,000 mg/day) coenzyme Q10 in ALS.
An open-label dose-escalation trial was performed to assess the safety and tolerability of high doses of coenzyme Q10 (CoQ10) in ALS. CoQ10, a cofactor in mitochondrial electron transfer, may improve the mitochondrial dysfunction in ALS. In this study, CoQ10 was safe and well tolerated in 31 subjects treated with doses as high as 3,000 mg/day for 8 months.
Amyotrophic Lateral Sclerosis↗
Seasonality of vitamin D status and bone turnover in patients with Crohn's disease.
BACKGROUND: While winter-time vitamin D deficiency has been well-documented in Crohn's disease patients, less is known about vitamin D status during summertime and whether a seasonal variation exists in bone turnover. AIMS: To compare vitamin D status and bone turnover markers in Crohn's disease patients with age- and sex-matched controls during late-summer and late-winter. SUBJECTS: Crohn's disease patients (n = 44; mean age 36.9 years, currently in remission) and matched controls (n = 44) were recruited from Cork University Hospital and Cork City area, respectively. METHODS: Bloods were analysed for 25-hydroxyvitamin D, parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin and urine analysed for N-telopeptides of type 1 collagen. RESULTS: Serum 25-hydroxyvitamin D concentrations were significantly (P < 0.003) lower in Crohn's disease patients than in control subjects during both seasons. In Crohn's disease patients, serum 25-hydroxyvitamin D concentrations were lower (P < 0.0001) whereas serum parathyroid hormone, osteocalcin and bone-specific alkaline phosphatase and urinary N-telopeptides of type 1 collagen levels were higher (P < 0.001) during late-winter than late-summer. CONCLUSION: There were notable seasonal variations in vitamin D status and bone turnover markers in Crohn's disease patients. The impact of winter decline in vitamin D status and increase in bone turnover on long-term risk of osteopenia/osteoporosis in Crohn's disease patients is unclear.
Adult↗
The infrapatellar fat pad: anatomy and clinical correlations.
This study examined the anatomy of the infrapatellar fat pad (IFP) in relation to knee pathology and surgical approaches. Eight embalmed knees were dissected via semicircular parapatellar incisions and each IFP was examined. Their volume, shape and constituent features were recorded. They were found in all knees and were constant in shape, consisting of a central body with medial and lateral extensions. The ligamentum mucosum was found inferior to the central body in all eight knees, while a fat tag was located superior to the central body in seven cases. Two clefts were consistently found on the posterior aspect of the IFP, a horizontal cleft below the ligamentum mucosum in six knees and a vertical cleft above, in seven cases. Our study found that the IFP is a constant structure in the knee joint, which may play a number of roles in knee joint function and pathology. Its significance in knee surgery is discussed.
Adipose Tissue↗
Intensity and direction of competitive anxiety as a function of goal attainment expectation and competition goal generation.
Jones's control model was adopted to investigate differences in the labelling of symptoms associated with pre-competition anxiety and self-confidence as a function of goal attainment expectation and competition goal generation. Team sport performers (N = 96) were divided into outcome, performance and process goal groups. Anxiety intensity and direction, and self-confidence were then examined as a function of goal expectancy (positive or negative) and perceived input into goal production (input or no input). MANOVA and follow-up ANOVA supported the study predictions. Specifically, participants who reported positive expectations of goal achievement and indicated some input into the goal generation process experienced the most facilitative interpretations of cognitive symptoms and greater self-confidence. The results highlight the need to consider how goals are generated when attempting to foster a sense of control and help athletes cope with the psychological demands of competition.
Adaptation, Psychological↗
Vitamin D intake and status in Irish postmenopausal women.
OBJECTIVE: The objective of this study was to assess vitamin D status during late-summer and late-winter/early-spring in postmenopausal Irish women, and whether it was influenced by vitamin D-containing supplement use. DESIGN: A longitudinal observational study. SETTING: Cork City, Ireland (51 degrees north). SUBJECTS: A total of 59 apparently healthy, free-living, postmenopausal women aged between 51 and 69 y were sampled during February/March 2002. Of these, 48 and 47 returned during August/September 2002 and February/March 2003, respectively. None of the women were suffering from any medical condition likely to affect vitamin D status. Fasting serums were collected and analysed for 25-hydroxyvitamin D (25 (OH) D) and parathyroid hormone (PTH) by enzyme immunoassays. RESULTS: Mean daily intake of vitamin D was 3.2 microg from food sources alone and 5.8 microg when vitamin D-containing supplements were included (P<0.01). Serum 25 (OH) D was significantly lower (P<0.001) during February/March 2002 than both August/September 2002 and February/March 2003. Serum 25 (OH) D was also significantly higher (P < or = 0.05) in women who were vitamin D-containing supplement users than nonusers during all three sampling points. Between 17 and 36% of women had inadequate vitamin D status (defined as serum 25 (OH) D <40 nmol/l) during late-winter, but only 4% had inadequate vitamin D status during late-summer. Serum 25 (OH) D was inversely related to serum PTH (r = -0.33; P = 0.028). CONCLUSION: Suboptimal vitamin D status is common in postmenopausal Irish women during winter. Vitamin D supplementation is associated with improved vitamin D status, even during summertime.
Aged↗
Test of radiation detectors used in homeland security applications.
This work was performed as part of the National Institute of Standards and Technology (NIST) program to support the development of the new American National Standards Institute (ANSI) standards N42.32-2003 and N42.33-2003 for hand-held detectors, and personal electronic dosimeters, as well as to support the Office of Law Enforcement Standards (OLES) and the Department of Homeland Security (DHS) in testing these types of detectors for their use by first responders. These instruments are required to operate over a photon energy range of 60 keV to 1.33 MeV and over a wide range of air-kerma rates. The performance and response of various radiation detectors, purchased by the NIST, was recorded when placed in 60Co, 137Cs, and x-ray beams at different air-kerma rates. The measurements described in this report were performed at the NIST x-ray and gamma-ray radiation calibration facilities. The instruments' response (exposure or dose rate readings) shows strong energy dependence but almost no dependence to different air-kerma rates. The data here reported provide a benchmark in support of current protocols that are being developed for radiation detection instrumentation used in homeland security applications. A future plan is to test these devices, plus other commercially available detectors, against ANSI standards N42.32-2003 and N42.33-2003.
Benchmarking↗
Spontaneous Clostridium septicum septic arthritis of the shoulder and gas gangrene. a case report.
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Aged↗
Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia.
BACKGROUND: High rates of osteoporosis in schizophrenia may result from the prolactin-raising effects of some antipsychotic medication. Aims To examine bone mineral density in relation to relevant endocrine variables in patients with schizophrenia taking prolactin-raising antipsychotics. METHOD: Fifty-five patients who had been receiving prolactin-raising antipsychotic medication for >10 years underwent dual-energy X-ray absorptiometry of their lumbar and hip bones. Among the endocrine variables assessed were plasma prolactin and sex hormones. RESULTS: Age-related reduced bone mineral density measures were found in 17 (57%) of the male and 8 (32%) of the female patients. Higher doses of the female patients. Higher doses of medication were associated with increased rates of both hyperprolactinaemia and bone mineral density loss. Bone loss for the whole group was correlated with medication dose, and for men was inversely correlated with testosterone values. CONCLUSIONS: These results suggest that patients with schizophrenia on long-term prolactin-raising antipsychotic medication are at high risk of developing reduced bone mineral density as a consequence of hyperprolactinaemia-induced hypogonadism.
Adult↗
Regional (spinal, epidural, caudal) versus general anaesthesia in preterm infants undergoing inguinal herniorrhaphy in early infancy.
BACKGROUND: With improvements in neonatal intensive care, more premature infants are surviving the neonatal period. With this increase, more are presenting for surgery in early infancy. Of predominance in this period is the repair of inguinal herniae, appearing in 38% of infants whose birth weight is between 751g and 1000g. Most postoperative studies show that approximately 20% to 30% of otherwise healthy former preterm infants having inguinal herniorrhaphy under general anaesthesia have one or more apnoeas in the postoperative period. Regional anaesthesia might reduce postoperative apnoea in this population. OBJECTIVES: To determine if regional anaesthesia, in preterm infants undergoing inguinal herniorrhaphy, reduces post-operative apnoea, bradycardia, and the use of assisted ventilation, in comparison to those infants undergoing inguinal herniorrhaphy with general anaesthesia. SEARCH STRATEGY: Randomised controlled trials were identified by searching MEDLINE (1966-Nov 2002), EMBASE (1982-Nov 2002), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2002), reference lists of published trials and abstracts published in Pediatric Research. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of spinal versus general anaesthesia in preterm infants undergoing inguinal herniorrhaphy in early infancy. DATA COLLECTION AND ANALYSIS: Data were extracted and the analyses performed independently by two reviewers. Authors of each eligible study were contacted for missing data. Studies were analysed for methodologic quality using the criteria of the Cochrane Neonatal Review Group. All data were analysed using RevMan 4.1. When possible meta-analysis was performed to calculate typical relative risk, typical risk difference, along with their 95% confidence intervals (CI). MAIN RESULTS: Four small trials comparing spinal with general anaesthesia in the repair of inguinal hernia were identified. One trial was excluded due to inadequate information. There was no statistically significant difference in the proportions of infants having postoperative apnoea/bradycardia, typical RR 0.69 (0.40, 1.21) or postoperative oxygen desaturations, RR 0.91 (0.61, 1.37). If infants having preoperative sedatives were excluded, then the meta-analysis supported a reduction in postoperative apnoea in the spinal anaesthetic group, typical RR 0.39 (0.19, 0.81). There was a reduction of borderline statistical significance in the use of postoperative assisted ventilation with spinal anaesthesia. There was an increase of borderline statistical significance in anaesthetic placement failure when spinal anaesthesia was attempted. REVIEWER'S CONCLUSIONS: There is no reliable evidence from the trials reviewed concerning the effect of spinal as compared to general anaesthesia on the incidence of post-operative apnoea, bradycardia, or oxygen desaturation in ex-preterm infants undergoing herniorrhaphy. The estimates of effect in this review are based on a total population of only 108 patients or fewer.A large well designed randomised controlled trial is needed to determine if spinal anaesthesia reduces post-operative apnoea in ex-preterm infants not pretreated with sedatives. Adequate blinding, follow up and intention to treat analysis are required.
Anesthesia, Conduction↗
A phase II study of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer.
AIM: The aim of this study was to evaluate the activity of the combination of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer (SCLC). Patients with good prognosis disease were included who were not medically fit to tolerate conventional chemotherapy. Activity was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Fifty-eight patients, 37 men and 21 women, with histologically or cytologically confirmed SCLC, who had bi-dimensionally measurable disease, with ECOG performance status > or = 2, with adequate haematological, hepatic and renal function received first-line chemotherapy with carboplatin (AUC x 5) day 1 and vinorelbine (30 mg/m2) days 1 and 8 of a 28-day cycle. Response was assessed after every two cycles of chemotherapy, with patients receiving a maximum of six cycles of treatment. RESULTS: The combination of carboplatin and vinorelbine is an active regimen in the treatment of SCLC, with an overall intention-to-treat response rate of 55% [95% confidence interval (CI): 42-68%] with six (10%) of patients having a complete response. Median time to progression was 18 weeks (95% CI: 15-21 weeks). Median overall survival was 26 weeks (95% CI: 21-31 weeks). Ten patients failed to complete two cycles of treatment, and were not evaluable for response for the following reasons: septic death (1 neutropaenic, 1 no myelotoxicity), non-toxic death (1 tumour eroded through the pulmonary artery, 1 ischaemic heart disease) ischaemic heart disease (1) and patient decision (5). There were a total of three toxic deaths all sepsis-complicating neutropaenia. Forty-four (76%) patients experienced grade 3 or 4 neutropaenia, six (11%) grade 3 or 4 thrombocytopaenia, 10 (13%) grade 3 lethargy, three (5%) grade 3 nausea and two (3%) grade 3 diarrhoea. CONCLUSIONS: The combination of carboplatin and vinorelbine is active against SCLC but the toxicity profile in this group of patients suggests that further evaluation is not appropriate.
Antineoplastic Combined Chemotherapy Protocols↗