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Andrew Klein

Publications and source records attributed to Andrew Klein.

7 recordsLinked to original sources
PubMed2006

Long-term mortality, cause of death, and temporal trends in complications after percutaneous aortic balloon valvuloplasty for calcific aortic stenosis.

We sought to assess survival, predictors of adverse outcomes, and complication rates in a more recent series of adults undergoing percutaneous aortic balloon valvuloplasty (PABV) for symptomatic calcific aortic stenosis. While aortic valve replacement is the treatment of choice for adults with symptomatic calcific aortic stenosis, PABV has been used in selected patients who are not good surgical candidates. Registries of patients who underwent PABV over 15 years ago have shown poor long-term survival and high procedural complication rates. This single-center cohort study enrolled consecutive adults undergoing PABV between 1989 and 2005 for calcific aortic stenosis. Demographic, hemodynamic, and procedural data, as well as vital status, were collected by chart review and query of the National Death Index. The study included 78 patients: mean age 78 +/- 11 years, 51% female, 90% heart failure, 61% coronary disease, and 8% end-stage renal disease. While 22% had a major procedural complication, this rate tended to decrease over time (P=0.068). In the cohort, 87% died with a median survival of 6.6 months. According to NDI records, the primary cause of death was cardiac in 54% of deaths. Survival was significantly higher in patients <or=70 years and those bridged to aortic valve replacement. PABV in patients who are elderly and not candidates for bridge to aortic valve replacement is associated with poor long-term survival. The decrease in the complication rate over the past 15 years has important implications regarding the morbidity associated with percutaneous aortic valve replacement techniques.

Adult↗
PubMed2005

The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix.

In a previous investigation, we demonstrated that mesenchymal stem cells (MSCs) actively migrated to cardiac allografts and contributed to graft fibrosis and, to a lesser extent, to myocardial regeneration. The cellular/molecular mechanism responsible for MSC migration, however, is poorly understood. This paper examines the role of CD44-hyaluronan interaction in MSC migration, using a rat MSC line Ap8c3 and mouse CD44-/- or CD44+/+ bone marrow stromal cells (BMSCs). Platelet-derived growth factor (PDGF) stimulation of MSC Ap8c3 cells significantly increased the levels of cell surface CD44 detected by flow cytometry. The CD44 standard isoform was predominantly expressed by Ap8c3 cells, accounting for 90% of the CD44 mRNA determined by quantitative real-time polymerase chain reaction. Mouse CD44-/- BMSCs bonded inefficiently to hyaluronic acid (HA), whereas CD44+/+ BMSC and MSC Ap8c3 adhered strongly to HA. Adhesions of MSC Ap8c3 cells to HA were suppressed by anti-CD44 antibody and by CD44 small interfering RNA (siRNA). HA coating of the migration chamber significantly promoted passage of CD44+/+ BMSC or Ap8c3 cells, but not CD44-/- BMSCs, through the insert membranes (p < .01). Migration of MSC Ap8c3 was significantly inhibited by anti-CD44 antibodies (p < .01) and to a lesser extent by CD44 siRNA (p = .05). The data indicate that MSC Ap8c3 cells, in response to PDGF stimulation, express high levels of CD44 standard (CD44s) isoform, which facilitates cell migration through interaction with extracellular HA. Such a migratory mechanism could be critical for recruitment of MSCs into wound sites for the proposition of tissue regeneration, as well as for migration of fibroblast progenitors to allografts in the development of graft fibrosis.

Animals↗
PubMed2003

Effects of intravenous nesiritide on human coronary vasomotor regulation and myocardial oxygen uptake.

BACKGROUND: Nesiritide, recombinant human B-type natriuretic peptide, has been shown to be efficacious in the treatment of decompensated heart failure. The effects of intravenous nesiritide on the human coronary vasculature have not been studied. METHODS AND RESULTS: Ten patients underwent right and left heart catheterization. Baseline coronary blood flow was determined using quantitative coronary angiography (QCA) and an intracoronary Doppler-tipped guidewire. Myocardial oxygen uptake was measured using a coronary sinus catheter. Patients then received an intravenous infusion of nesiritide (2 microg/kg bolus followed by 0.01 microg/kg per min infusion) for 30 minutes. Right atrial pressure decreased 52% (P=0.012), pulmonary artery mean pressure decreased 19% (P=0.03), pulmonary capillary wedge pressure decreased 46% (P=0.002), and mean arterial pressure decreased 11% (P=0.007). QCA demonstrated a 15% increase in coronary artery diameter from a baseline of 2.6+/-0.8 to 3.0+/-0.8 mm at 30 minutes (P=0.007). The coronary velocity measure of average peak velocity increased 14% from 20.8+/-6.4 at baseline to 23.8+/-7.2 cm/s at 5 minutes (P=0.015) and then returned to baseline for the remainder of the infusion. Coronary blood flow increased 35% (P=0.007), whereas coronary resistance decreased 23% at 15 and 30 minutes (P=0.036). Myocardial oxygen uptake decreased 8% during the nesiritide infusion (P=0.043). CONCLUSIONS: Nesiritide exerts coronary vasodilator effects on both the coronary conductance and resistance arteries. Despite a decrease in coronary perfusion pressure, coronary artery blood flow is increased, coronary resistance is decreased, and myocardial oxygen uptake is decreased.

Adult↗
PubMed2002

Interleukin-12-induced cytotoxicity against syngeneic B cell lymphomas of SJL/J mice.

The B cell lymphomas (RCS) that develop spontaneously in 90% of aging SJL/J mice stimulate syngeneic CD4+ Vbeta16+ Th2 cells to produce cytokines, such as IL-4 and IL-5, which promote lymphoma growth. Although RCS cells express a unique superantigen (vSAg) encoded by an endogenous MMTV (Mtv-29) provirus that also elicits IFN-gamma production from naïve syngeneic lymphoid cells, there is no development of RCS-specific cytotoxicity. However, addition of IL-12 to co-cultures of SJL spleen and irradiated (gamma-)RCS cells resulted in the appearance of effector cells that killed RCS and NK-susceptible target cells. Antibody depletion studies revealed at least two types of RCS/IL-12-induced cytotoxic cells: (1) NK cells (Asialo GM1+) and (2) CD8+ CTL. Despite high titers of IFN-gamma in the SN of co-culture of SJL spleen and gamma-RCS cells, cytotoxicity only developed if IL-12 was also included in the co-cultures. The results of RNAse protection assays and multi-parameter FACS analysis demonstrated an upregulation of IFN-gamma and decrease in IL-4 by activated Th cells in co-cultures with IL-12. These results indicate that inclusion of IL-12 in primary co-cultures of SJL spleen and gamma-RCS cells influences the qualitative nature of the response to favor use of RCS-responsive Th1 rather than Th2 cells to facilitate the production of cytotoxic effector cells. Results of in vivo experiments support this hypothesis, as judged by tumor growth assays and FACS analysis of the tumor cell content of lymphoid tissues. Inhibition of lymphoma growth was observed in mice given gamma-RCS/IL-12-induced effector cells prior to injection of viable RCS cells. These results demonstrate that IL-12 can be used to alter the host immune response leading to induction of cytotoxic effector cells that inhibit the development and/or progressive growth of otherwise resistant B cell lymphomas in SJL/J mice.

Animals↗