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Biomedical subjects

P Reilly

Publications and source records attributed to P Reilly.

At least 37 records · Page 2Linked to original sources

Diffuse neuronal perikaryon amyloid precursor protein immunoreactivity in a focal head impact model.

Amyloid precursor protein (APP) has been shown to accumulate in traumatically injured axons as early as 1 hour after injury. This accumulation may be due to interruption of fast axoplasmic transport and/or upregulation of APP synthesis. The aim of this study was to examine the neuronal cell body response to head impact using APP immunostaining in a focal non-missile head impact model. Ten anaesthetised and ventilated 2 year old Merino ewes were subjected to graded impact in the left temporal region by captive bolt. 2 hours after impact the brain was perfused fixed with formaldehyde. The tissue was mounted in paraffin, sectioned and stained with a monoclonal antibody to APP and standard H&E stain. APP positivity was semi-quantitated using a modification of our previously described sector scoring system [1]. Widespread neuronal APP positivity was found in the cerebral hemispheres and brain stem distant from the site of focal injury in all 10 animals. The most prominent APP positivity was found in the nerve cell bodies of the impacted left cerebral hemisphere. APP positive neurons were also found within regions which were structurally normal when stained with H&E. These results demonstrate diffuse neuronal perikaryon APP immunoreactivity following a focal head impact injury. The expression of APP within the neuronal cell body may be due to upregulation of APP synthesis or alterations in the availability of epitopes of APP. Further studies are in progress to address these hypotheses.

Amyloid beta-Protein Precursor↗

Long-term in vivo cochlear transgene expression mediated by recombinant adeno-associated virus.

Adeno-associated virus (AAV) integrated transgene expression within guinea pig cochlea has been previously documented. This article extends these studies by characterizing the AAV-mediated gene transfer for duration of transgene expression within the cochlea and its effect upon cochlear cytoarchitecture over a period of 6 months. All animals infused with AAV expressed the transgene product, bacterial beta-galactosidase (beta-gal) enzyme, in the spiral limbus, spiral ligament, spiral ganglion cells and the organ of Corti at 2-24 weeks after infusion. However, the level of beta-gal expression, as determined from intensity of immunoreactivity, was relatively lower at 24 weeks as compared with 2 weeks. The cellular and tissue architecture within the AAV-beta-gal perfused cochleae, harvested 2-8 weeks after AAV infusion, was generally intact, ie free from inflammation and cellular degeneration. However, cellular degeneration and degradation was apparent in the cochleae of some but not all animals harvested at 12 and 24 weeks after AAV infusion.

Animals↗

Teenage mothers and their peers: a research challenge.

Recent reports have highlighted the adverse health experience of teenage mothers. The question of how these mothers' perceptions of their own health status and social networks differ from those of their nulliparous peers is explored in this pilot study, which highlights some practical problems associated with research in this important field.

Adolescent↗

A clinical trial of a financial incentive to go to the tuberculosis clinic for isoniazid after release from jail.

SETTING: Screening for active tuberculosis (TB) and providing isoniazid (INH) preventive therapy in jails are important control measures. In San Francisco, however, historical data showed that 62% of inmates were released before completing preventive therapy, and of those only 3% attended the TB Clinic for follow-up. OBJECTIVE AND DESIGN: A randomized clinical trial to compare a $5 cash incentive plus standardized TB education with standardized TB education alone in encouraging released inmates to make a first visit to the clinic. RESULTS: Of 79 persons enrolled in the trial, 77.2% were released before INH completion. Rates of first visit were not significantly different for those receiving +5 plus standardized education (25.8%) versus standardized education alone (23.3%), but were higher than rates seen in historical data for inmates not receiving standardized education. Age was an important predictor of completion of a first visit (odds ratio 1.09, 95% confidence interval 1.02-1.16, P = 0.017). Other variables predicting adherence included intent to adhere, more previous time in jail, stable housing, and being partnered versus alone, although these were not statistically significant. CONCLUSION: Standardized education may be important in improving follow-up after release. Further work on the role of a financial incentive in this population is needed.

Adult↗

A software architecture to support a large-scale, multi-tier clinical information system.

A robust software architecture is necessary to support a large-scale multi-tier clinical information system. This paper describes our mechanism for enterprise distribution of applications and support files, the consolidation of data-access functions and system utilities stored on the data access tier, and an application framework which implements a coherent clinical computing environment. The software architecture and systems described in this paper have been robust through pilot testing of our applications at Massachusetts General Hospital.

Computer Security↗

Pediatric nonpowder firearm injuries: outcomes in an urban pediatric setting.

BACKGROUND: Approximately 32 000 nonpowder firearm injuries are reported annually with more than 60% occurring in the pediatric population. Case reports of serious and fatal injuries have been described; however, no large inclusive series have been published. We reviewed an 11-year experience of an urban pediatric emergency department to evaluate the circumstances, spectrum of injuries, and outcomes attributable to nonpowder firearms. METHODS: A retrospective, descriptive case series of all children 18 years of age or younger evaluated at an urban children's hospital from January 1983 through December 1994 were eligible for study. Patients were identified using a computerized database, the National Electronic Injury Surveillance System, and the trauma registry in the department of surgery. Medical records were reviewed to collect demographic information, circumstances of injury, anatomic site and type of injury, treatment, and outcomes for nonpowder firearm injuries. RESULTS: One hundred eighty patients were identified, and a complete data set was available for 166 (92%). The mean age was 12 +/- 3.7 years, 24% of children were <10 years old, and 71% of the children were male. Three patients returned with a second nonpowder firearm injury during the study period. Forty-nine percent of injuries were intentional and 44% of all injuries occurred during the summer and early fall months. The most common sites of injury were the extremity/buttocks (39%), head and neck (33%), thorax (13%), and eye (8%). Serious injuries included intracranial hemorrhage, cardiac right ventricle laceration, hyphema, and abdominal visceral injury (liver laceration, pancreatic laceration, intestinal perforation). The majority of wounds required local wound care, and the children (74%) were discharged from the emergency department. Of the patients admitted to the hospital (27%), 45% required operative intervention. There were no deaths. Seven percent (12/166) of patients sustained some functional deficit with 42% (5/12) the result of an ocular injury. CONCLUSION: The majority of nonpowder firearm injuries are minor; however, the potential for serious injury should not be underestimated. Minor injuries can be treated with local wound care and tetanus prophylaxis, and patients can be discharged from the emergency department. Education of parents and children to the potential risks associated with these weapons is essential. Stricter regulations regarding ownership of nonpowder firearms and mandatory safety instruction should be considered.

Adolescent↗

Mice lacking the myotonic dystrophy protein kinase develop a late onset progressive myopathy.

Myotonic dystrophy (DM) is an autosomal dominant disorder resulting from the expansion of a CTG repeat in the 3' untranslated region of a putative protein kinase (DMPK). To elucidate the role of DMPK in DM pathogenesis we have developed Dmpk deficient (Dmpk-/-) mice. Dmpk-/-mice develop a late-onset, progressive skeletal myopathy that shares some pathological features with DM. Muscles from mature mice show variation in fibre size, increased fibre degeneration and fibrosis. Adult Dmpk-/-mice show ultrastructural changes in muscle and a 50% decrease in force generation compared to young mice. Our results indicate that DMPK may be necessary for the maintenance of skeletal muscle structure and function and suggest that a decrease in DMPK levels may contribute to DM pathology.

Animals↗

General practice data retrieval: the Northern Ireland project.

OBJECTIVE: To develop an epidemiological database of morbidity in the community as presented to general practitioners and to support epidemiological research in general practice. DESIGN: The project is a sentinel network of 23 general practices in Northern Ireland that report the incidence of a list of selected diseases to a central unit for analysis. RESULTS: Results are presented for depression, diabetes, and myocardial infarction. The age--sex distributions of diabetes and myocardial infarction are comparable with other published data but the incidence of depression is under estimated. CONCLUSIONS: The importance of complete accuracy of data reported within sentinel networks depends on the purposes for which information is to be used. For some diagnoses, such as diabetes and acute myocardial infarction, the accuracy of the reported incidence is high while for other diseases, such as depression, where diagnostic behaviour varies more between doctors, the figures are much less reliable.

Adolescent↗

Physician responsibility in conducting genetic testing.

The rapid growth of DNA-based tests raises complex questions about how to integrate them efficiently into clinical medicine and about the medicolegal consequences of rapidly shifting standards of practice. Standards of practice change in response to many factors; the most important are guidelines promulgated by professional bodies or published comments by opinion leaders, malpractice litigation, and legislation. Recently, human geneticists have successfully shaped the clinical use of tests for Huntington's disease and carrier screening for cystic fibrosis. Clinical geneticists, oncologists, and others should work together now to develop practice standards for the use of new DNA-based predictive tests for breast, colon, and other cancers.

Ethics, Medical↗

The hemostatic effects of desmopressin on patients who had total joint arthroplasty. A double-blind randomized trial.

The effects of desmopressin on postoperative bleeding and postoperative transfusion requirements were studied in ninety-two hemostatically normal patients who had had an elective primary total hip or total knee arthroplasty. The patients were randomized into either a placebo or a desmopressin group in a double-blind prospective clinical trial. During closure of the wound, desmopressin (0.03 microgram per kilogram of body mass) or the placebo was infused into a peripheral vein over a twenty-minute period. Compared with the placebo, desmopressin did not significantly decrease blood loss or transfusion requirements, and it did not affect the postoperative platelet or fibrinogen levels or the bleeding time. The results were no different even when the treatment and control groups were matched according to surgeon, use of cement for the femoral and knee components, preoperative use of non-steroidal anti-inflammatory agents, or performance of a lateral release for total knee arthroplasty. We concluded that desmopressin does not reduce blood loss or transfusion requirements after total joint arthroplasty.

Aged↗

Mutation analysis and haplotype correlation for 139 cystic fibrosis patients from the Nebraska Regional Cystic Fibrosis Center.

Cystic fibrosis (CF) is the most common autosomal recessive disorder in Caucasian populations with an approximate frequency of one in 2,500 live births and a carrier frequency of one in 25. We studied 400 individuals seen at The Nebraska Regional Cystic Fibrosis Center that included 139 CF patients, 206 parents, and 55 unaffected siblings to determine the frequency of the delta F508, R117H, G542X, S549R/N, G551D, R553X, R560T, and W1282X mutations. In addition, we determined haplotypes on each of these individual's chromosomes using four markers that included XV-2c, KM-19, pMP6d.9, and G2. Results from this study showed that the delta F508 mutation was present in 70% of CF chromosomes. Of the 139 CF patients 74 (53%) were homozygous for the delta F508 deletion, 47 (34%) were heterozygous for the delta F508 deletion and an unknown mutation, and 18 (13%) carried two unknown mutations. Four additional mutations were also found in our population and included G542X (6%), G551D (5%), R553X (4%), and R560T (1%). One patient was documented to be a compound heterozygote for G542X/G551D. A polymorphism, F508C, that has previously been reported in several families was also present in our study. The most common haplotype associated with the delta F508 deletion in our CF patients was the E haplotype (CF Consortium B) while other mutations were associated with a variety of haplotypes.

Base Sequence↗

Immunogold localization of the DnaK heat shock protein in Escherichia coli cells.

Previously reported cell fractionation experiments have yielded conflicting information on the cellular localization of the DnaK heat shock protein of Escherichia coli. Here we used immunogold labelling of ultra-thin sections to determine the localization of DnaK in unstressed cells at 30 degrees C as well as in heat-shocked cells. In cells grown at 30 degrees C, gold particles were found predominantly in the cytoplasm, indicating that the majority of the DnaK molecules are cytoplasmic; however, a fraction of the gold particles was located in proximity to the membranes, raising the possibility that a subpopulation of DnaK proteins is membrane-associated. Heat shock of the cells did not induce detectable relocalization of DnaK.

Antibodies, Bacterial↗

Immunocytochemical analysis of poly-beta-hydroxybutyrate (PHB) synthase in Alcaligenes eutrophus H16: localization of the synthase enzyme at the surface of PHB granules.

Antibodies raised against the Alcaligenes eutrophus poly-beta-hydroxybutyrate (PHB) synthase polypeptide were used for immunocytochemical localization of the synthase enzyme in whole cells and purified PHB granules. The data presented demonstrate for the first time that the synthase enzyme is located on the surface of the PHB granule rather than being incorporated inside the granule during its formation. From these basic observations and data from the recent literature, a model of granule assembly is proposed.

Acyltransferases↗

Malignant astrocytoma in South Australia: treatment and case survival.

Kernohan grade III and IV astrocytomas are usually fetal and in the past have had a case survival rate of only about 10% two years from diagnosis. Data on 285 cases registered at the Royal Adelaide Hospital in 1977-1986 showed a median survival of approximately six months. The survival rate was 25% at one year and 15% at two years. Survival reduced markedly with increase in age at diagnosis from a two-year rate of 53% for patients under 40 years of age to 5% for patients aged 70 years or more. This may have been due in part to the more frequent treatment of younger patients by decompression and radiotherapy. Apart from age and treatment mode, factors related to extended survival included a longer duration of symptoms before diagnosis and location of the tumour in the frontal lobes. Notwithstanding prospects for an increase in short-term survival from the use of radiotherapy as an adjunct to surgery, long-term outcomes for these neoplasms are still very poor.

Adult↗