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David Fitchett

Publications and source records attributed to David Fitchett.

20 records · Page 2Linked to original sources

Preventing thrombosis: update of first-line therapy in the management of non-ST segment elevation acute coronary syndromes.

Non-ST segment elevation acute coronary syndrome (NSTE ACS) has a high rate of recurrence. Both antithrombotic and antiplatelet agents in association with coronary revascularization play an important role in the prevention of an adverse outcome. Acetylsalicylic acid, heparin and low molecular weight heparin (especially enoxaparin), and the intravenous small-molecule glycoprotein IIb/IIIa inhibitors, are of proven value. Recently, clopidogrel has been shown to reduce recurrent ischemic events, both early and during the first year after the index ACS. Furthermore, two recent trials have shown that an early invasive strategy is preferable to a conservative approach in the higher risk patient. As yet, no study has shown either the efficacy or the safety of combining all these treatment modalities in the management of the NSTE ACS patient. The initial choice of antithrombotic and antiplatelet agents and a strategy for early revascularization is made after considering the risk of recurrent acute ischemic events. For patients destined to have an early invasive strategy, it is desirable to choose an anti-thrombotic/antiplatelet combination that will reduce events before revascularization, enhance the revascularization procedure and not be associated with excessive bleeding. A risk-determined algorithm is presented, which applies observations made at the time of presentation to decide the optimal management for the individual patient.

Acute Disease↗

DNA integrity and transgene expression after passage through the NOGA needle catheter used for therapeutic myocardial angiogenesis.

BACKGROUND: The NOGA (Biosense Webster, Markham, ON, Canada) injection catheter is an innovative navigational device that provides an ideal platform for intra-myocardial injection material. However, injection through a long (1.91 m), narrow (27G) nitinol needle could result in deterioration in the integrity and functionality of DNA. METHODS: To test this possibility, DNA in plasmid form (pcDNA3.1) containing the Lac Z transgene (250 micro l) was passed through the NOGA needle using a hand-held 1 cc syringe at a gentle hand injection pressure (43 +/- 3 PSI, 3.0 +/- 0.2 kg/cm(2)) or at maximal manual pressure (90 +/- 6 PSI, 6.3 +/- 0.4 kg/cm(2)), either once or 20 times. This DNA, compared to DNA not passed through the NOGA needle (control), was then used to transfect primary cultures of rat skin fibroblasts (FB) from Fisher 344 rats and the cells were subsequently stained for beta galactosidase (betagal). RESULTS: Transfection efficiency was significantly reduced by passing the DNA through the needle at both 43 +/- 3 PSI (78 +/- 4% of control, n = 10, P < 0.05 versus control) and 90 +/- 6 PSI (66 +/- 4 % of control, n = 10, P < 0.01 versus control, P < 0.02 versus 43 +/- 3 PSI). Passage of the DNA through the NOGA needle 20 times resulted in a transfection efficiency of only 5 +/- 1% of control (n = 20, P < 0.1 x 10(-11) versus control). Capillary Electrophoresis revealed that the reduction in transfection efficiency was due to a conformational change in the DNA from predominantly supercoiled to nicked and linearized DNA. Transfection efficiency as compared with control decreased as the concentration of the DNA solution which was passed through the needle was increased from 0.3 micro g/ micro l to 2.4 micro g/ micro l. Recovery experiments confirmed that the reduction in transfection efficiency was not due to loss of DNA by binding to the NOGA needle. CONCLUSION: These results suggest that DNA is susceptible to shear forces when injected through the NOGA needle even at nominal clinical injection pressures, suggesting that careful and controlled injections will be required to achieve optimal gene integrity and expression.

Journal Article↗