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Biomedical subjects

M McCarthy

Publications and source records attributed to M McCarthy.

At least 73 records · Page 4Linked to original sources
PubMed2001

Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene.

Female BALB/c mice are unusually radiosensitive and more susceptible than C57BL/6 and other tested inbred mice to ionizing radiation (IR)-induced mammary tumors. This breast cancer susceptibility is correlated with elevated susceptibility for mammary cell transformation and genomic instability following irradiation. In this study, we report the identification of two BALB/c strain-specific polymorphisms in the coding region of Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit, which is known to be involved in DNA double-stranded break repair and post-IR signal transduction. First, we identified an A --> G transition at base 11530 resulting in a Met --> Val conversion at codon 3844 (M3844V) in the phosphatidylinositol 3-kinase domain upstream of the scid mutation (Y4046X). Second, we identified a C --> T transition at base 6418 resulting in an Arg --> Cys conversion at codon 2140 (R2140C) downstream of the putative leucine zipper domain. This unique PrkdcBALB variant gene is shown to be associated with decreased DNA-dependent protein kinase catalytic subunit activity and with increased susceptibility to IR-induced genomic instability in primary mammary epithelial cells. The data provide the first evidence that naturally arising allelic variation in a mouse DNA damage response gene may associate with IR response and breast cancer risk.

Amino Acid Sequence↗
PubMed2001

Radial glial cell line C6-R integrates preferentially in adult white matter and facilitates migration of coimplanted neurons in vivo.

C6-R is a cell line derived from C6 glioma cells that exhibits key properties of radial glia including the ability to support neuronal migration in culture. To explore its potential use in promoting neuronal migration in vivo, we analyzed the behavior of C6-R cells in the intact and injured adult rat CNS. At 6-11 days postimplantation at the splenium of the corpus callosum, green fluorescent protein-labeled C6-R cells were observed primarily in either the corpus callosum or the hippocampus in the brain, and in the spinal cord they migrated more extensively in the white matter than in the grey matter. To determine whether C6-R cells retain their ability to promote neuronal migration in vivo, they were coinjected with labeled neurons into adult brain. When rat embryonic neurons were coimplanted with C6-R cells, the neurons and C6-R cells comigrated through a much larger volume than neurons alone or neurons coimplanted with fibroblasts. In brains preinjured with ibotenic acid, C6-R cells as well as coimplanted neurons distributed widely within the lesion site and migrated into adjacent brain tissue, while transplants with neurons alone were restricted primarily to the lesion site. The results suggest that radial glial cell lines can serve as a scaffold for neuronal migration that may facilitate development of experimental models for neural transplantation and regeneration.

Animals↗
PubMed2001

Changes in health-related quality of life following coronary artery bypass graft surgery.

BACKGROUND: There are limited data to help clinicians identify patients likely to have an improvement in quality of life following CABG surgery. We evaluated the relationship between preoperative health status and changes in quality of life following CABG surgery. METHODS: We evaluated 1,744 patients enrolled in the VA Cooperative Processes, Structures, and Outcomes in Cardiac Surgery study who completed preoperative and 6-month postoperative Short Form-36 (SF-36) surveys. The primary outcome was change in the Mental Component Summary (MCS) and Physical Component Summary (PCS) scores from the SF-36. RESULTS: On average, physical and mental health status improved following the operation. Preoperative health status was the major determinant of change in quality of life following surgery, independent of anginal burden and other clinical characteristics. Patients with MCS scores less than 44 or PCS scores less than 38 were most likely to have an improvement in quality of life. Patients with higher preoperative scores were unlikely to have an improvement in quality of life. CONCLUSIONS: Patients with preoperative health status deficits are likely to have an improvement in their quality of life following CABG surgery. Alternatively, patients with relatively good preoperative health status are unlikely to have a quality of life benefit from surgery and the operation should primarily be performed to improve survival.

Activities of Daily Living↗
PubMed2001

Cervical spine instability: clearance using dynamic fluoroscopy.

Cle aring the cervical spine in a multiply injured trauma patient is a dilemma because clinical examination for ligamentous instability cannot be performed, and the standard cervical spine series can miss isolated ligamentous injury. Static flexion/extension views are unsafe, as the obtunded patient has no protective reflexes and cannot complain of pain during the exam. This results in a need for prolonged spinal immobilization and its attendant complications. Dynamic fluoroscopy may be useful in the detection of otherwise occult injuries.We performed a prospective study of a cervical spine clearance algorithm incorporating dynamic fluoroscopy with flexion/extension views. Inpatient records over a 3-year period were reviewed. Patient demographic data, results of cervical spine films and fluoroscopic exams, interventions based on positive results, and missed injuries were recorded.One hundred ten patients with normal spine plain films underwent dynamic fluoroscopy with flexion and extension views of the cervical spine. The average Glasgow Coma Score was 9.2 and the average revised Trauma Score was 9.5. Nine patients had evidence of cervical instability on exam. Six of these were deemed stable by the orthopedic or neurosurgical spine consultants, and these patients had their hard collars removed. One patient with positive findings had cervical immobilization with hard collar continued, a second had halo placement, and a third underwent spinal fusion for atlanto-occipital disassociation. No patients undergoing dynamic fluoroscopy were subsequently found to have missed cervical spine injury.With our protocol, 3 patients had significant cervical instability that would have been missed without dynamic fluoroscopy. Given the significant medical and legal ramifications of missed cervical spine injury and the benefits of early removal of cervical collars, more widespread use of dynamic fluoroscopy of the cervical spine is warranted.

Journal Article↗
PubMed2001

User focus groups and Best Value in services for people with learning disabilities.

This paper examines the problems and potentials of employing user focus groups as part of an approach to defining and reviewing Best Value in local authority and jointly commissioned services for people with learning disabilities. Drawing on experience from three local authority initiatives and wider experience with Best Value, the paper describes the development of user focus groups for helping review adult placement, outreach and day services for people with learning disabilities. The key methodological considerations for consulting with service users with learning disabilities through focus groups are identified and the interpretation of outcomes considered. The paper concludes with pointers for the effective operation of user focus groups in local authority Best Value reviews of services for people with learning disabilities, of use to practitioners, service managers and commissioners.

Adult↗
PubMed2001

Contribution of age and gender to outcome of blunt splenic injury in adults: multicenter study of the eastern association for the surgery of trauma.

BACKGROUND: The purpose of this study was to examine the contribution of age and gender to outcome after treatment of blunt splenic injury in adults. METHODS: Through the Multi-Institutional Trials Committee of the Eastern Association for the Surgery of Trauma (EAST), 1488 adult patients from 27 trauma centers who suffered blunt splenic injury in 1997 were examined retrospectively. RESULTS: Fifteen percent of patients were 55 years of age or older. A similar proportion of patients > or = 55 went directly to the operating room compared with patients < 55 (41% vs. 38%) but the mortality for patients > or = 55 was significantly greater than patients < 55 (43% vs. 23%). Patients > or = 55 failed nonoperative management (NOM) more frequently than patients < 55 (19% vs. 10%) and had increased mortality for both successful NOM (8% vs. 4%, p < 0.05) and failed NOM (29% vs. 12%, p = 0.054). There were no differences in immediate operative treatment, successful NOM, and failed NOM between men and women. However, women > or = 55 failed NOM more frequently than women < 55 (20% vs. 7%) and this was associated with increased mortality (36% vs. 5%) (both p < 0.05). CONCLUSION: Patients > or = 55 had a greater mortality for all forms of treatment of their blunt splenic injury and failed NOM more frequently than patients < 55. Women > or = 55 had significantly greater mortality and failure of NOM than women < 55.

Adult↗