Biomedical subjects

David McCollum

Publications and source records attributed to David McCollum.

5 recordsLinked to original sources

PubMed2006

COMPARE: comparison of the effects of carvedilol CR and carvedilol IR on left ventricular ejection fraction in patients with heart failure.

Left ventricular ejection fraction (LVEF) is an important measure of ventricular function in the evaluation of heart failure. Immediate-release (IR) carvedilol twice daily has been shown to improve LVEF in subjects with ischemic and nonischemic chronic heart failure. A once-daily formulation, controlled-release (CR) carvedilol, is expected to improve quality of care through improved adherence as a result of the reduced frequency of dosing. This multicenter, randomized, double-blind study in subjects with stable chronic heart failure will compare the change in LVEF in patients receiving carvedilol IR with those receiving carvedilol CR. LVEF will be measured by 2-dimensional echocardiography at 6 months after entry into the maintenance period of the study drug. The secondary objectives of this study are to assess changes in left ventricular remodeling and function, to evaluate changes in brain natriuretic peptide levels, and to determine the incidence of all-cause and heart failure-related hospitalizations and all-cause mortality after treatment with carvedilol CR or carvedilol IR.

Administration, Oral↗

PubMed2006

Argatroban therapy in heparin-induced thrombocytopenia with hepatic dysfunction.

STUDY OBJECTIVES: We evaluated the dosing requirements in argatroban-treated patients with heparin-induced thrombocytopenia (HIT) and hepatic dysfunction, and compared efficacy and safety outcomes with historical control patients. DESIGN: Retrospective analysis. SETTING: Inpatient setting. PATIENTS: Patients with hepatic dysfunction, defined as total bilirubin > 25.5 micromol/L (1.5 mg/dL), aspartate aminotransferase >100 IU/L, and/or alanine aminotransferase >100 IU/L, were identified from previous multicenter, historical-controlled studies of argatroban therapy in HIT. INTERVENTIONS: Argatroban, adjusted to maintain activated partial thromboplastin times (aPTTs) 1.5 to 3 times baseline in the experimental group, vs no direct thrombin inhibition in the historical control patients. MEASUREMENTS AND RESULTS: The analysis population included 82 argatroban patients and 34 historical control patients with hepatic impairment, of whom approximately 50% in each group had renal dysfunction (defined as a serum creatinine level > 1.3 mg/dL). The argatroban dosage was 1.6 +/- 1.1 microg/kg/min (mean +/- SD) over a mean 5-day course of therapy. Significantly lower doses were used in patients with elevated vs normal total bilirubin levels (0.8 +/- 0.6 microg/kg/min vs 1.7 +/- 0.8 microg/kg/min, p = 0.0063) and in patients with hepatic/renal dysfunction vs hepatic dysfunction alone (1.2 +/- 1.1 microg/kg/min vs 2.0 +/- 1.1 microg/kg/min, p < 0.001). The aPTT 24 h after argatroban initiation was 69 +/- 22 s, with 80% of patients having a therapeutic level of anticoagulation. Thirty-four argatroban-treated patients (41.5%) and 17 control patients (50.0%) experienced the 37-day composite end point of death, amputation, or new thrombosis (p = 0.32). Argatroban significantly reduced new thrombosis (8.5% vs 26.5%, p = 0.012). Major bleeding was similar between treatment groups (4.9% vs 2.9%, p = 0.684). CONCLUSIONS: Hepatic dysfunction affects argatroban dosing, with reduced doses required particularly in patients with serum total bilirubin levels > 25.5 micromol/L (1.5 mg/dL) or combined hepatic/renal dysfunction. Individual mean aPTT-adjusted doses typically remain > or = 0.5 microg/kg/min, supporting the recommendation of 0.5 microg/kg/min as a conservative initial dose for most patients with hepatic impairment. Argatroban, with proper initial dosing and monitoring, can provide safe and effective antithrombotic therapy in patients with HIT and hepatic impairment.

Aged↗

PubMed2006

How frequently is venous thromboembolism in heparin-treated patients associated with heparin-induced thrombocytopenia?

BACKGROUND: Patients receiving heparin for thromboprophylaxis or treatment may have new or recurrent venous thromboembolism (VTE) if immune-mediated heparin-induced thrombocytopenia (HIT) occurs or for other reasons, eg, if anticoagulation fails. We estimated from the literature how frequently a patient presenting with VTE during or following heparin therapy has HIT-associated VTE. METHODS: A comprehensive, systematic literature search was conducted to identify studies using unfractionated or low-molecular-weight heparin (LMWH) for thromboprophylaxis or treatment in which new or recurrent VTE and serologically confirmed HIT were reported. From extracted study data, the proportion of patients with HIT-associated VTE relative to any VTE was calculated by heparin type and mode of administration. RESULTS: We identified 10 studies, some with multiple arms, that used unfractionated heparin (IV administration, 5 studies; subcutaneous administration, 3 studies) or subcutaneous LMWH (5 studies) and met analysis criteria. Across these studies, 386 of 6,219 heparin-treated patients had VTE, including 32 patients who also had HIT. The frequency of HIT-associated VTE among heparin-treated patients with VTE was comparable between IV and subcutaneous unfractionated heparin therapy (13.2% [17 of 129 patients] vs 12.4% [14 of 113 patients]; odds ratio, 1.07; 95% confidence interval, 0.50 to 2.3; p > 0.99) yet significantly different between unfractionated heparin and LMWH therapy (12.8% [31 of 242 patients] vs 0.7% [1 of 144 patients]; odds ratio, 21.0; 95% confidence interval, 2.8 to 156; p < 0.001). CONCLUSIONS: VTE is associated with HIT infrequently (< 1%) in LMWH-treated patients, yet often (approximately one in eight cases) in unfractionated heparin-treated patients. Physicians should suspect the possibility of HIT if VTE develops during or soon after unfractionated heparin use; if thrombocytopenia is present, alternative anticoagulation should be used until HIT is excluded.

Anticoagulants↗

PubMed2006

Child maltreatment and brain development.

A growing body of research has linked childhood experiences of maltreatment with a host of physical conditions that manifest in adulthood. In addition, newer neuroimaging techniques have documented structural changes that occur in the brains of individuals who suffer early maltreatment. This article briefly reviews the literature on these topics and outlines the connection between abuse in childhood and health problems in adulthood.

Adolescent↗

PubMed2002

Methylene blue restores spatial memory retention impaired by an inhibitor of cytochrome oxidase in rats.

Cytochrome oxidase is the mitochondrial enzyme that catalyzes the utilization of oxygen for the electron transport chain during cellular respiration. Chronic subcutaneous infusion of sodium azide, an inhibitor of cytochrome oxidase, produced a spatial memory retention deficit in rats in a holeboard maze. Methylene blue, which has been shown to increase oxygen consumption in vitro, was used to restore mitochondrial electron transport in order to facilitate memory consolidation. Administration of 1 mg/kg methylene blue after training, during the memory consolidation period, completely restored the memory retention impaired by the inhibitor of cytochrome oxidase. This suggests that methylene blue may compensate for impaired mitochondrial respiration and improve spatial memory retention. Memory retention deficits found in some neurodegenerative diseases may be improved by drugs targeting impaired mitochondrial respiration.

Analysis of Variance↗