Outcomes research in amyotrophic lateral sclerosis: lessons learned from the amyotrophic lateral sclerosis clinical assessment, research, and education database.

Objective: To examine the care of patients with ALS following the publication of the standardized recommendations for the management of patients with amyotrophic lateral sclerosis (ALS) published in 1999 by the American Academy of Neurology.

Methods: Specific aspects of ALS patient management have been evaluated serially using a national Amyotrophic Lateral Sclerosis Clinical Assessment, Research, and Education (ALS CARE) database to encourage compliance with these recommendations and to assure continuing quality improvement.

Results: The most recent analysis of 5,600 patients shows interesting epidemiological observations and treatment trends.

Responses of fathead minnows (Pimephales promelas) during life-cycle exposures to pulp mill effluents at four long-term receiving water study sites.

We exposed fathead minnows (Pimephales promelas to 7 concentrations of effluents from pulp mills at 4 Long-Term Receiving Water Study (LTRWS) sites. The primary objective of these investigations was to determine the potential for toxicity, particularly on fish reproduction, of the pulp mill effluents using laboratory tests. These tests were performed as LTRWS fish community assessments were being completed, thus results of the laboratory fish reproduction tests could be compared to in-stream fish community measurements.

Patient clinical factors influencing use of hysterectomy in New York, 2001-2005.

Objective: To determine the effect of patient clinical factors on the utilization of hysterectomy and alternatives of hysterectomy.

Study Design: The database of Empire Blue Cross Blue Shield was abstracted for all claims relating to a hysterectomy procedure or a hysterectomy-associated diagnosis during the 48 consecutive months of May 2001-April 2005. Two hundred ninety-five thousand one hundred forty-eight claim lines were abstracted and analyzed by CPT and diagnostic grouping codes.

Allelic methylation bias of the RARB2 tumor suppressor gene promoter in cancer.

Retinoic acid receptor B2 (RARB2) is frequently inactivated in cancer. Methylation in the 5'-untranslated region and first exon is known to play a role; however, few studies have analyzed the detailed methylation pattern of the promoter region. We show that hypo- and hypermethylated alleles coexist in 5/11 cell lines in which RARB2 is inactivated.

Effect of physician gender and specialty on utilization of hysterectomy in New York, 2001-2005.

Objective: The purpose of this study was to determine the effect of physician gender and specialty on the utilization of hysterectomy and alternatives to hysterectomy.

Study Design: The database of Empire Blue Cross Blue Shield was abstracted for all claims relating to a hysterectomy procedure or a hysterectomy-associated diagnosis during the 48 consecutive months May 2001-April 2005. Two hundred ninety-five thousand, one hundred forty-eight claim lines were abstracted and analyzed by CPT and diagnostic grouping codes.

HIV-1-Associated Neuropathies.

Peripheral neuropathy associated with human immunodeficiency virus type 1 (HIV-1) infection is a major cause of morbidity in this patient population. Due to the associated chronic pain, its management has come within the purview of neuropsychiatrists. This paper will focus on the primary pathogenic aspects of HIV-1-associated peripheral neuropathies.

c-kit is required for cardiomyocyte terminal differentiation.

c-kit, the transmembrane tyrosine kinase receptor for stem cell factor, is required for melanocyte and mast cell development, hematopoiesis, and differentiation of spermatogonial stem cells. We show here that in the heart, c-kit is expressed not only by cardiac stem cells but also by cardiomyocytes, commencing immediately after birth and terminating a few days later, coincident with the onset of cardiomyocyte terminal differentiation. To examine the function of c-kit in cardiomyocyte terminal differentiation, we used compound heterozygous mice carrying the W (null) and W(v) (dominant negative) mutations of c-kit.

Paraneoplastic cerebellar degeneration in ovarian carcinoma: case report with review of immune modulation.

Paraneoplastic cerebellar degeneration (PCD) is a rare nonmetastatic complication of a carcinoma. It is typically mediated by antibodies generated against tumor antigens. These antigens are the same proteins as expressed on Purkinje cells within the cerebellum; immune activation in the central nervous system (CNS) results in the syndrome.

New techniques in radical hysterectomy.

Purpose Of Review: To review the recent literature regarding modifications of abdominal radical hysterectomy as well as development of new approaches including laparoscopic, vaginal, and robotic radical hysterectomy.

Recent Findings: Nerve-sparing radical hysterectomy technique allows for significant reduction in postoperative bladder morbidity. Radical vaginal hysterectomy with laparoscopic lymph node dissection is a well-recognized technique that offers excellent cure rates with absence of abdominal entry as well as reduced postoperative febrile and gastrointestinal morbidity.

Endometrial carcinoma expresses an increased cathepsin B/D ratio.

Objectives: Cathepsins B and D belong to a family of proteases involved in tumor invasion and metastasis. As such they may function as biomarkers for the aggressiveness of a given tumor. We examined the enzymatic activity of these proteins as well as the cellular and extracellular distribution of cathepsins B and D.

Inhibition of Rho via Arg and p190RhoGAP in the postnatal mouse hippocampus regulates dendritic spine maturation, synapse and dendrite stability, and behavior.

The RhoA (Rho) GTPase is a master regulator of dendrite morphogenesis. Rho activation in developing neurons slows dendrite branch dynamics, yielding smaller, less branched dendrite arbors. Constitutive activation of Rho in mature neurons causes dendritic spine loss and dendritic regression, indicating that Rho can affect dendritic structure and function even after dendrites have developed.

Genome-wide association study for Crohn's disease in the Quebec Founder Population identifies multiple validated disease loci.

Genome-wide association (GWA) studies offer a powerful unbiased method for the identification of multiple susceptibility genes for complex diseases. Here we report the results of a GWA study for Crohn's disease (CD) using family trios from the Quebec Founder Population (QFP). Haplotype-based association analyses identified multiple regions associated with the disease that met the criteria for genome-wide significance, with many containing a gene whose function appears relevant to CD.

Phase II/III randomized trial of TCH346 in patients with ALS.

Background: TCH346 exerts antiapoptotic effects by binding to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and blocking the apoptotic pathway in which GAPDH is involved. Apoptosis is considered to be a key pathogenic mechanism in neurodegenerative diseases including ALS.

Methods: Patients were randomly assigned in a double-blind fashion to receive either placebo or one of four doses of TCH346 (1.

The Abl-related gene tyrosine kinase acts through p190RhoGAP to inhibit actomyosin contractility and regulate focal adhesion dynamics upon adhesion to fibronectin.

In migrating cells, actin polymerization promotes protrusion of the leading edge, whereas actomyosin contractility powers net cell body translocation. Although they promote F-actin-dependent protrusions of the cell periphery upon adhesion to fibronectin (FN), Abl family kinases inhibit cell migration on FN. We provide evidence here that the Abl-related gene (Arg/Abl2) kinase inhibits fibroblast migration by attenuating actomyosin contractility and regulating focal adhesion dynamics.