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Biomedical subjects

Brian Sweeney

Publications and source records attributed to Brian Sweeney.

6 recordsLinked to original sources
PubMed2006

The novel Tau mutation G335S: clinical, neuropathological and molecular characterization.

Mutations in Tau cause the inherited neurodegenerative disease, frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known coding region mutations cluster in the microtubule-binding region, where they alter the ability of tau to promote microtubule assembly. Depending on the tau isoforms, this region consists of three or four imperfect repeats of 31 or 32 amino acids, each of which contains a characteristic and invariant PGGG motif. Here, we report the novel G335S mutation, which changes the PGGG motif of the third tau repeat to PGGS, in an individual who developed social withdrawal, emotional bluntness and stereotypic behavior at age 22, followed by disinhibition, hyperorality and ideomotor apraxia. Abundant tau-positive inclusions were present in neurons and glia in the frontotemporal cortex, hippocampus and brainstem. Sarkosyl-insoluble tau showed paired helical and straight filaments, as well as more irregular rope-like filaments. The pattern of pathological tau bands was like that of Alzheimer disease. Experimentally, the G335S mutation resulted in a greatly reduced ability of tau to promote microtubule assembly, while having no significant effect on heparin-induced assembly of recombinant tau into filaments.

Adult↗
PubMed2005

Modulation of immune cell function by polyunsaturated fatty acids.

The n-3 and n-6 polyunsaturated fatty acids (PUFAs) are essential dietary constituents. They are important as a source of energy, as structural components of cell membranes, and as signalling molecules. They have been demonstrated to be potent modulators of the immune response, and research has endeavoured to optimise the ratio of n-3 to n-6 PUFAs in the lipid component of total parenteral nutrition (TPN) to optimise their beneficial effects in the clinical setting. Critically ill neonates on TPN have an increased incidence of sepsis, and additional studies have determined that lipid emulsions depress various elements of cellular immune responses in monocytes, lymphocytes, and neutrophils. It has been proposed that PUFAs may mediate their manifold effects through the modification of eicosanoid production and by directly or indirectly modifying intracellular signal transduction pathways, including the alteration of gene transcription, in various tissues. They are susceptible to lipid peroxidation, and there is evidence that the products of this process may result in cell death by apoptosis, a nonphlogistic homeostatic process of cell deletion. PUFAs have been shown to induce apoptosis in primary lymphocytes, colonic mucosal cells, and various cell lines. Additionally, our laboratory has shown them to be potent inducers of apoptosis in neonatal monocytes. This may represent a novel mechanism whereby PUFAs may modify the immune response.

Animals↗
PubMed2005

Preparedness of hospitals to respond to a radiological terrorism event as assessed by a full-scale exercise.

Hospitals and healthcare workers face the challenge of being prepared to manage victims of acts of terrorism that involve chemical, biological, and radiological agents that they do not commonly encounter. One example that is often cited as a potential terrorism scenario is the use of a conventional explosive that is mixed with radioactive material. On November 10, 2004, we conducted a regional multihospital full-scale exercise involving 11 hospitals and 358 victim-observers to evaluate hospital preparedness for such an event. Our results demonstrate that hospitals are not adequately prepared to manage mass casualties with associated radiological contamination.

Disaster Planning↗
PubMed2003

Effect of cocaine use on bone marrow-mediated erythropoiesis.

OBJECTIVES: Cocaine-mediated erythrocytosis is one of several effects that cocaine may have on hematologic indices; however, the precise mechanism by which cocaine induces peripheral erythrocytosis is not fully understood. The objective of this study was to examine the contribution of the bone marrow to cocaine-mediated erythrocytosis. METHODS: Differences in mean hemoglobin concentration, hematocrit, and reticulocyte counts were measured in consecutive cocaine-exposed and cocaine-unexposed patients who presented to the emergency department (ED) with chest pain. Acute cocaine exposure (<3 hours) was confirmed by history and toxicologic analysis of the urine on all patients. Means were compared using independent-samples t-test and covariates were examined using multiple regression. RESULTS: Seventy-nine patients met enrollment criteria. Hemoglobin and hematocrit levels were significantly elevated in the cocaine-using subjects (13.5/39.8) compared with controls (12.6/37.7; p < 0.02). However, no corresponding elevation in reticulocyte count (p = 0.2) was observed. Multivariate logistic regression revealed that male chest pain patients were significantly more likely to be exposed to cocaine (OR 5.15 [95% CI = 1.77 to 15.3]) than females (p = 0.001), and all relative increases in hemoglobin concentration in the cocaine-exposed group were attributable to gender. Cocaine exposure was not significantly associated with reticulocyte count. Multivariate linear regression revealed that of demographic, medical, and substance use covariates, only a history of diabetes mellitus was significantly associated with an elevated reticulocyte count (p = 0.009). CONCLUSIONS: Acute cocaine exposure is not associated with erythrocytosis in younger ED patients with chest pain. The lack of an elevated reticulocyte count suggests that bone marrow does not contribute to any transient erythrocytosis that may occur.

Adolescent↗
PubMedDate not supplied

Large-scale urban disaster drill involving an explosion: lessons learned by an academic medical center.

Disaster drills are an effective way to test a hospital's preparedness for real-life disasters, but an extensive amount of coordination and time is necessary to host a successful drill with a large number of victims. The lessons learned in this drill include a number of planning, education, orientation, and follow-up issues. It is not realistic to believe that a drill can be perfectly planned and practiced; therefore each drill provides another opportunity to improve on past experience.

Academic Medical Centers↗