Showing papers by "Atlantic Health System published in 2004"

Bench-to-bedside review: Fundamental principles of acid-base physiology

Abstract: Complex acid–base disorders arise frequently in critically ill patients, especially in those with multiorgan failure. In order to diagnose and treat these disorders better, some intensivists have abandoned traditional theories in favor of revisionist models of acid–base balance. With claimed superiority over the traditional approach, the new methods have rekindled debate over the fundmental principles of acid–base physiology. In order to shed light on this controversy, we review the derivation and application of new models of acid–base balance.

Long-term rhythm control of drug-refractory atrial fibrillation with "hybrid therapy" incorporating dual-site right atrial pacing, antiarrhythmic drugs, and right atrial ablation.

Abstract: We evaluated the long-term efficacy, safety, and applicability of a "hybrid" therapy strategy for rhythm control in atrial fibrillation (AF), incorporating dual-site right atrial pacing, antiarrhythmic drugs, and right atrial ablation. One hundred thirteen patients (paroxysmal AF [n = 70], persistent/permanent AF [n = 43]) with refractory symptomatic AF were treated with this strategy and followed for 1 to 81 months (mean 30 +/- 23). All-cause mortality, AF recurrences, and progression to permanent AF were monitored and recorded by implanted device data logs. There was no procedural mortality. Rhythm control was achieved in 90% of all patients at 3 and 5 years, with comparable efficacy in subpopulations with paroxysmal (98%), persistent, or permanent AF (87%, p >2). Overall survival was 84% at 3 years and 80% at 5 years, and was higher in patients with paroxysmal AF than in patients with persistent or permanent AF (86% vs 67% at 4 years, p <0.001). Patients with persistent or permanent AF had a greater need for cardioversion (p <0.004) and right atrial ablation (p <0.04) than patients with paroxysmal AF to achieve comparable rhythm control. A hybrid therapy strategy can provide safe and effective long-term rhythm control in patients with drug-refractory AF, and can be implemented in subpopulations presenting with paroxysmal, persistent, or permanent AF.

Gene expression after crush injury of human saphenous vein: using microarrays to define the transcriptional profile.

Abstract: Background Vein graft stenosis is believed to be the pathophysiologic response of vascular tissue to injury and is the major cause of vein graft failure. Therapeutic interventions might improve with knowledge of the physiologic pathways involved in the hyperplastic response to vascular injury. In this study, our purpose was to identify induced, early pathways that might be important in the human response to vascular injury. Study design Human saphenous vein from 7 patients was organ cultured or crush injured and cultured for 48 or 72 hours after harvest. Gene expression was determined for syngeneic veins at harvest and at the experimental time points and compared to determine which genes were induced or repressed. Expressed genes (the transcriptional profile) were then assigned to functional physiologic classes. Results At 72 hours, in both organ-cultured and crush-injured vein, the gene for the Wnt ligand protein ( WNT5A ) was induced. At 48 hours in the organ-cultured vein only, the gene for the Frizzled protein ( FZD2 ), a subunit of the Wnt receptor complex, was repressed. At 72 hours in injured vein only, the gene for the product of Wnt signaling ( WISP1 ) was induced; the gene for the Wnt-binding, soluble Frizzled-related protein ( FRZB ) was repressed; and the gene for Dickkopf ( DKK1 ) protein, which binds to the low density lipoprotein receptor-related protein subunit of the Wnt receptor complex, was induced. Conclusions Early induction of WNT5A , coupled with the coordinated induction and repression of genes that modulate the Wnt signaling pathway, led to the early, selective induction of WISP1 and no other Wnt-inducible genes. This early, selective expression of a limited gene set might characterize the human vascular response to injury, and could enable development of therapies to treat the clinical sequelae of this response.

Cystic fibrosis presenting as new onset diabetes mellitus in adolescent twins

Abstract: We describe identical adolescent twin girls who presented with symptoms consistent with type 1 diabetes. Medical work up for evaluation of gastrointestinal symptoms led to a diagnosis of cystic fibrosis (CF) in both. These cases suggest that diabetes can be a presenting symptom of CF in the absence of pulmonary symptomatology.

Comparative chemotactic properties of WISP-1 and PlGF on human venous smooth muscle cells

Abstract: Introduction: Wnt-Inducible Secreted Protein-1 (WISP-1) and Placental Growth Factor (PlGF) were found to be induced within 72 hours in organ-cultured human saphenous vein. While both are members of the PDGF superfamily, WISP-1 is closely related to Connective Tissue Growth Factor and PlGF is closely related to VEGF. During vascular wound repair, WISP-1 may recruit vascular smooth muscle cells (VSMCs) and PlGF may recruit endothelial cells because of their respective similarities to previously characterized growth factors. We hypothesized that WISP-1 may be more effective at inducing migration of human VSMCs than PlGF. Methods: Lyophilized recombinant proteins (R&D Systems, Minneapolis, MN) were reconstituted in RPMI1640. Passage 4 VSMCs, all derived from a single saphenous vein for a single experiment, were used at 10,000 cells/well in 48-well chemotaxis chambers (Neuroprobe, Gaithersburg, MD). Each experiment was repeated 4 times using cells from a different saphenous vein for each experiment. Results: Both WISP-1 and PlGF induced a chemotactic response from the VSMCs. WISP-1 was maximally chemotactic at 1 ng/mL (approximately 0.026 nM) while the PlGF maximum was 10 ng/mL (approximately 0.36 nM). Further studies will define their differential chemotactic effect on endothelial cells. Conclusions: WISP-1 was 13.8 times more effective, on a molar basis, than PlGF at inducing VSMC chemotaxis. While both growth factors probably play a role in vascular wound repair, their performance in chemotaxis assays of VSMCs suggests that WISP-1 activity is directed toward VSMCs.