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Biomedical subjects

Matthew Sullivan

Publications and source records attributed to Matthew Sullivan.

4 recordsLinked to original sources

Cellular prion protein is increased in the plasma and peri-infarcted brain tissue after acute stroke.

The physiologic properties of the normal cellular prion protein (PrP(C)) have not been established fully, although recent evidence showed its upregulation in cerebral ischaemia. Using patients, animal models, and in vitro studies we aimed to identify in detail the expression and localization of PrP(C) in ischemic stroke. Patients in acute phase of ischaemic stroke had increased plasma levels of circulating PrP(C) as compared to healthy age- and gender-matched controls (3.1 +/- 1.4 vs. 1.9 +/- 0.7 ng/ml, P = 0.002). Immunohistochemistry showed increased expression of PrP(C) in the soma of peri-infarcted neurones as well as in the endothelial cells (EC) of micro-vessels and inflammatory cells in peri-infarcted brain tissue from patients who survived for 2-34 days after an initial stroke. The same pattern was repeated 1-48 hr after MCAO. RT-PCR showed increased gene expression of PrP(C) by human foetal neurons (HFN) after 12 hr of oxygen glucose deprivation (OGD), which remained increased after 24 hr reperfusion. Western blotting confirmed that protein expression was similarly upregulated, and fluorescent labeling showed a notable increase in peri-nuclear and axonal PrP(C) staining intensity. Increased plasma PrP(C) seems to reflect endogenous expression in acute stroke-affected brain tissue. Increased cellular expression in peri-infarcted regions may influence hypoxia-induced cell damage, although the effects on EC survival and angiogenesis remain to be elucidated.

Acute Disease↗

Enhancing the continuum are for substance abusers.

BACKGROUND: In 2001, Pikes Peak Mental Health Center (Colorado Springs, Colorado) spearheaded a community collaboration to increase service capacity for substance abusers and reduce recidivism. In 2003, a Substance Abuse Advisory Council generated community support through substance abuse education activities and fund raising. It developed a program that entailed a recovery home and shelter for clients, intensive case management, and outpatient programs. METHODS: A task force was initiated to develop community solutions. Each stakeholder evaluated the issue of substance abuse as it related to his or her agency's perspective and collaborated to develop solutions within a broader community context. The project's goals were to (1) establish community awareness regarding the discrepancies between quality in care and the complex interactions of substance abuse variables, (2) eliminate the fragmentation between care providers, and (3) produce an enhanced continuum of care. RESULTS: Improvements were evident in all six performance measures (p < .05)--detoxification access, services, and continuum of care. For example, overall reduction in the recidivism rate has shown a 23% decrease since the project's inception. Capacity increased by 42% from 2004 to 2005. Since 2003, self-referrals to the detoxification unit have increased by 44%. DISCUSSION: On the basis of the outcomes, Pikes Peak Mental Health Center's Detoxification/Acute Unit has obtained funding to continue and expand existing services to target the indigent behavioral health community.

Awards and Prizes↗

Improving services by holding hands, not pointing fingers.

Imagine a community with a social detox center decreasing its number of beds, along with facing gaps in linkages from detox to outpatient treatment because of funding cuts. This results in overcrowded and misused emergency rooms filled with intoxicated people, and patients leave before being seen. Law-enforcement needs increase to respond to inebriatedpeople on the streets. Community agencies become increasingly frustrated and mistrustful of each other. The community essentially is in crisis because of substance abuse issues.

Colorado↗

Randomized trial of FX high flux vs standard high flux dialysis for homocysteine clearance.

BACKGROUND: Cardiovascular disease is the major cause of death in the end-stage renal disease population. Novel risk factors such as homocysteine (Hcy) are of considerable interest in this group as hyperhomocysteinaemia is highly prevalent in the setting of renal impairment. Folic acid-vitamin B group therapies are only partially effective treatments. Hcy is highly protein-bound and thus poorly dialysed. Dialyzers with albumin-leaking properties have been shown to result in lowering of plasma Hcy. As the FX-class (Advanced Fresenius Polysulfone dialyzer) has greater clearance of larger molecular weight substances but is non-albumin-leaking, we explored the capacity of this new technology membrane to reduce plasma Hcy levels. METHODS: A prospective randomized cross-over trial in 35 prevalent haemodialysis patients, one group receiving 12 weeks dialysis using FX dialyzer then 12 weeks with standard high flux dialysis (SHF) and the other group SHF followed by FX dialyzer. All patients received vitamin B(6) 25 mg and folic acid 5 mg daily throughout the study. RESULTS: The primary outcome was plasma Hcy pre-dialysis at week 12. FX vs SHF showed no significant difference, 25+/-6.6 vs 25.9+/-5.8 microg/l, Delta95% CI = -2.77 to 4.59, P = 0.31. There was a non-significant trend toward a decrease in Hcy in both groups (27.43+/-7.68 to 25.91+/-5.78 micromol/l for SHF, P = 0.23 and 26.0+/-4.58 to 25.0+/-6.61 micromol/l for FX, P = 0.28). Analysis by repeated measures method demonstrated a statistically significantly lower Hcy with FX vs SHF dialyzer (adjusted beta = -1.30, 95% CI = -2.41 to -0.19, P = 0.022). K(t)/V(urea) was higher in FX vs SHF (1.35+/-0.18 vs 1.22+/-0.2; P = 0.013). Folate and B(6) levels did not change. CONCLUSIONS: The primary outcome analysis did not show any significant difference in pre-Hcy comparing FX and SHF membranes. Although our secondary analysis demonstrated a statistically significant difference between membranes, the magnitude of the difference (1.3 mumol/l) is not clinically significant. Thus the use of the FX dialyzer did not result in a clinically significant benefit in relation to improving pre-dialysis Hcy compared with standard high-flux dialysis.

Adult↗