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Biomedical subjects

S O'Grady

Publications and source records attributed to S O'Grady.

9 recordsLinked to original sources

Utility of zanamivir for chemoprophylaxis of concomitant influenza A and B in a complex continuing care population.

OBJECTIVE: To describe compliance with and the safety and prophylactic efficacy of zanamivir among patients at risk of developing influenza-related complications after exposure to both influenza A and B viruses. DESIGN: Nonrandomized trial using both historical and contemporaneous controls from ward populations within the same facility. SETTING: A 547-bed urban hospital providing complex continuing care and rehabiltation. PATIENTS: Fifty patients on a single ward concomitantly exposed to both influenza A and B during an influenza outbreak. INTERVENTIONS: All patients were screened for symptoms of influenza and nasopharyngeal swabs were sent for viral culture prior to treatment (two oral inhalations [2 x 5 mg] twice daily for 5 days) or prophylaxis (two oral inhalations [2 x 5 mg] once daily for 14 days) with zanamivir. Patient symptoms, compliance, and drug tolerance were monitored daily. Demographic data, comorbidities, vaccination status, and functional status (Katz score) were collected for all patients. RESULTS: The mean age of the patients was 70.6 years (standard deviation, +/- 16.4 years). Ninety-four percent had two or more comorbidities, 71% were dependent in two or more activities of daily living, 63% had been vaccinated for influenza, and 82% had received amantadine. Zanamivir was well tolerated, with 93% of the patients completing their course. The efficacy for preventing symptomatic infection was 82% and 91% (95% confidence interval, 62% to 98%) based on historical and contemporaneous controls, respectively. CONCLUSION: These data suggest that zanamivir can be used safely and effectively as a prophylactic agent in the management of influenza outbreaks in a complex continuing care population with multiple comorbidities.

Aged↗

The utility of polysporin ointment in the eradication of methicillin-resistant Staphylococcus aureus colonization: a pilot study.

We evaluated the efficacy of an ointment containing bacitracin, polymyxin B, and gramicidin for the eradication of colonization by methicillin-resistant Staphylococcus aureus in 11 medical patients, 10 (91%) of whom had previously failed a 1-week course of topical mupirocin. Mupirocin resistance was documented in 5 (45%) of 11 patients. Successful decolonization was achieved in 9 (82%) of 11 patients (based on 2 months of follow-up).

Aged↗

C3a is made by proximal tubular HK-2 cells and activates them via the C3a receptor.

BACKGROUND: Some individual components of complement are synthesized by the kidney. However, it is not known whether these form functional pathways that are able to mediate more fundamental cellular events. We examined the ability of HK-2 tubular cells to produce an intact alternative pathway of complement and to respond to the C3a fragment thus produced through the C3a receptor. METHODS: The production of mRNA for alternative pathway components was detected by reverse transcription-polymerase chain reaction, whereas protein synthesis was investigated by probing Western blots of concentrated culture supernatants with polyclonal antisera. Levels of C3a and inositol phosphate produced by HK-2 cells were determined by radioimmunoassay, whereas those of transforming growth factor-beta1 (TGF-beta1) were measured by ELISA. Intracellular tyrosine phosphorylation in response to C3a was evaluated by Western blotting and chemiluminescence. RESULTS: HK-2 cells produce the complement polypeptides C3a, C3, and factors B and H. They also contain mRNA for all components of the alternative pathway and the C3a receptor. mRNA levels were up-regulated by interleukin-1alpha, interleukin-1beta, and tumor necrosis factor-alpha. Incubation of HK-2 cells with C3a led to an increase in intracellular inositol phosphate and to tyrosine phosphorylation of at least two proteins in a pertussis-toxin-sensitive fashion. C3a and C3a desarg also up-regulated the secretion of TGF-beta1 by these cells. CONCLUSION: HK-2 cells produce an intact alternative pathway of complement. In addition, both locally produced and urinary C3a have the potential to activate these cells, resulting in inflammatory events such as TGF-beta1 production.

Cells, Cultured↗

The influence of oral lipid loads on acylation stimulating protein (ASP) in healthy volunteers.

OBJECTIVES: To examine the hypothesis that a sustained rise in plasma acylation stimulating protein (ASP, C3a desarg) accompanies the elevation in triacylglycerol that follows the ingestion of an oral fat load. DESIGN: Following an overnight fast, blood samples were obtained from healthy volunteers while fasting and 15 min, 1, 2, 4, 6 and 8 h following ingestion of: (i) a liquid meal, rich in dairy fat (eight subjects) and (ii) a semi-liquid meal, with higher total fat content and rich in polyunsaturated fat (six subjects). SUBJECTS AND METHODS: Four male and four female volunteers (age range: 22-51 y; body mass index (BMI): 17.9-26.9 kg/m2) received the first meal. Six subjects (age range: 32-60 y; BMI: 18.0-28.4 kg/m2), including three from the first study, received the second meal using the same protocol. ASP and C5a were measured by radioimmunoassay (RIA) and the complement proteins C3, factor B and C5 by radial immunodiffusion or nephelometry. Tumour necrosis factor (TNF)-alpha was measured by enhanced ELISA, and plasma cholesterol and triacylglycerol by an automated enzymatic method. The presence of chylomicrons was assessed in post-prandial plasma samples taken after the second meal. RESULTS: There was no significant change in mean ASP concentration in either group at any time point, following ingestion of either meal. However, there was a significant positive linear trend in ASP following the second fat challenge (ANOVA; P < 0.05). There was also no change in complement proteins, plasma cholesterol or TNF-alpha. Plasma triacylglycerol rose significantly after the first and second meals (P < 0.05 and P < 0.001 at 2 h post-prandially); the mean maximum rise above the fasting level was 58 +/- 41% and 89 +/- 38% respectively (mean +/- s.d.). Chylomicrons were detected in samples taken from each subject after the second meal. Analysis of individual ASP data showed a sustained rise in one subject after the first meal and two subjects after the second meal. Substantial variation in ASP concentration was observed in samples taken in the first 2 h post-prandially. CONCLUSION: There was no significant change in ASP nor other complement proteins for either group of subjects following ingestion of the lipid loads. Individual data showed substantial variation in post-prandial ASP, but multiple plasma sampling did not define the basis for this variation.

Adult↗

Detection and quantification of the control proteins of the alternative pathway of complement in 3T3-L1 adipocytes.

The complement peptide C3a desarg is identical to acylation-stimulating protein (ASP), a human plasma protein that potently stimulates adipocyte triacylglycerol synthesis and glucose transport. Both human and murine adipocytes express mRNA and/or protein for the complement components C3 and factors B and D (adipsin) required to generate ASP. However, the regulatory mechanisms controlling this process are unknown. We have established a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique to demonstrate the presence in mouse 3T3-L1 adipocytes of mRNA for all components of the alternative pathway, including the control proteins factors I and H, CR1 and properdin. On differentiation, mRNA for C3 (fivefold) and factor D (> 50-fold) increased, whereas stimulation with tumour necrosis factor (TNF)-alpha and interleukin (IL) 1 beta led to eightfold increases in factor B mRNA. Metabolic labelling followed by immunoprecipitation showed that factor B protein is normally present in small quantities, and is greatly increased by cytokine stimulation. The larger quantities of C3 and H proteins present were little affected, whereas levels of C3a increased on cytokine stimulation. These results suggest that the rate-limiting step in the cytokine-induced production of ASP in adipocytes is factor B synthesis.

3T3 Cells↗

Matching needs to services: the quick response. Case study: St George Hospital and Community Health Services Best Practice Project.

A Quick Response Program (QRP) was developed and implemented at St George Hospital during 1995 and 1996. The program sought to improve the service provided to elderly people presenting to the emergency department by offering a new rapid response service pathway to community-based care. Emergency department discharge planning and crisis intervention evolved as important QRP functions during the program's life. Evaluation findings indicated that QRP penetration into the elderly sub-acute emergency department patient population was high, and that hospital admissions were avoided without affecting emergency department process times. Health outcomes were not compromised by the program, and patient and general practitioner satisfaction were high. The program grappled with the inherent conflict of interest between the aims of the hospital (acute care services) and those of the community service (support and maintenance). The program sought to bridge the gap between these service parameters in the name of meeting patient needs.

Aftercare↗

AIDS classification and the military.

In 1985 the U.S. Department of Defense took action to establish regulations for the protection of national defense personnel against the AIDS epidemic. Since that time specific procedures have been carried out in each military unit to effectively handle soldiers infected with the AIDS virus. A unique six-stage classification system for monitoring disease progression of AIDS is currently used in military medical facilities around the world, and military medicine remains active in the fight against AIDS.

Acquired Immunodeficiency Syndrome↗