Biomedical subjects

L Macgregor

Publications and source records attributed to L Macgregor.

3 recordsLinked to original sources

PubMed2006

Donor methylenetetrahydrofolate reductase genotype is associated with graft-versus-host disease in hematopoietic stem cell transplant patients treated with methotrexate.

Methotrexate (MTX), used as a graft-versus-host disease (GvHD) prophylactic agent in hematopoietic stem cell transplantation (HSCT), exerts its effect via folate cycle inhibition. A critical enzyme involved in folate metabolism is 5,10-methylenetetrahydrofolate reductase (MTHFR). We examined the association of a single nucleotide polymorphism (SNP) at position 677 in the MTHFR gene on GvHD outcomes in allogeneic HSCT patients administered MTX. MTHFR genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 193 HSCT patients and donors. A total of 140 patients were transplanted with an HLA-matched related donor and 53 with an unrelated donor. GvHD outcomes were compared between genotypes by univariate and multivariate analysis. The combined donor 677CT and TT genotypes were associated with a decreased incidence of GvHD (acute and chronic combined) in HSCT recipients with an HLA-matched related donor (75% at 1 year in the CT and TT group compared with 91% in the wild type CC group, P=0.01), increased time to onset of first GvHD (P=0.001) and time to first GvHD treated with systemic therapy (P=0.022). Unrelated donor MTHFR genotype was not associated with outcome parameters and no associations of recipient genotype in either related or unrelated donor cohorts were observed.

Adolescent↗

PubMed2005

Clinical practice guidelines: barriers to durability after effective early implementation.

BACKGROUND: Clinical practice guidelines in general (General-CPG) may reduce variation in clinician performance and improve patient outcomes. Short-term evaluation is now routine, but demonstration of early successful implementation does not necessarily ensure longer-term effectiveness. AIM: To assess adherence to chronic obstructive pulmonary disease (COPD)-CPG recommendations at the Royal Melbourne Hospital (RMH), 2 years after successful implementation. To identify barriers to sustained success of General-CPG. METHODS: A multi-faceted evaluation was performed to document: (i) current adherence to COPD management recommendations (medical record audit); (ii) awareness of attitudes towards and barriers for the use of COPD-CPG and General-CPG (staff survey, focus groups and key informant interviews) and (iii) access to and quality of available General-CPG (internet review and random sample General-CPG evaluation. RESULTS: Adherence to COPD-CPG recommendations was highly variable. Adherence was higher in the Emergency Department than the general wards and for specific therapeutic recommendations. It was lower for non-pharmacological therapy and for recommendations relating to processes of care. Most health professionals were in favour of General-CPG. Barriers to use of General-CPG were in keeping with previous literature reports. Organizational issues including high levels of staff turnover and lack of integration of General-CPG into hospital quality frameworks were highlighted as major barriers. Hospital intranet access and presentation of General-CPG identified lack of consistency in terminology and presentation. CONCLUSION: Short-term effectiveness of COPD-CPG implementation did not ensure sustained success. Departmental organizational behaviours and organizational system barriers are major factors influencing durability.

Aged↗

PubMed1996

Failure of allopurinol to improve left ventricular stroke work after cardiopulmonary bypass surgery.

OBJECTIVE: This study examined the effects of allopurinol on global left ventricular function after coronary artery bypass surgery. DESIGN: A randomized prospective partially blinded study in 52 patients undergoing elective coronary artery bypass surgery. SETTING: Conducted in a university-affiliated tertiary care facility. INTERVENTIONS: Participants received 400 mg of allopurinol 18 hours and 400 mg of allopurinol orally 3 hours before surgery or no allopurinol. Patients then received a standard anesthetic technique consisting of target-controlled opiate infusion and inhalation anesthesia. Coronary artery bypass was performed using moderate hypothermia and oxygenated crystalloid cardioplegia. MEASUREMENTS AND MAIN RESULTS: Global left ventricular function was assessed by means of left ventricular stroke work index (LVSWI) calculated before and after induction of anesthesia and after cardiopulmonary bypass at 15 minutes, 6, 12 and 24 hours. There was no difference in the LVSWI before or after surgery when the two groups were compared. CONCLUSIONS: In this population sample, the use of preoperative allopurinol did not result in improved left ventricular stroke work after coronary artery bypass surgery.

Adult↗