Evaluation of a New Closed-System Automated RT-qPCR Assay for the Rapid Detection and Monitoring of Common Nucleophosmin Mutations in Patients with Acute Myeloid Leukemia.

Quantitative assessment of nucleophosmin 1 () mutation status is integral to evaluating measurable residual disease (MRD) in -mutated acute myeloid leukemia (AML) patients. In a retrospective study, leftover peripheral blood (PB) specimens (n = 40) which were collected for routine clinical diagnostic evaluations of AML disease burden were tested by both a novel automated RT-qPCR quantitative NPM1 assay (Xpert NPM1 mutation assay) and the NPM1 mutA, mutB&D MutaQuant kit. Based on a Deming regression analysis, there was a high correlation (slope = 0.

Use of rhodamine B as a biomarker in a simulated oral vaccine deployment against bovine tuberculosis in white-tailed deer.

Introduction: Free-ranging white-tailed deer () in northeastern lower Michigan, (United States) are a self-sustaining reservoir for bovine tuberculosis (bTB). Farm mitigation practices, baiting bans, and antlerless deer harvests have been ineffective in eliminating bTB in white-tailed deer and risks to cattle. The apparent prevalence has remained relatively constant in deer, prompting interest among wildlife researchers, managers, and veterinarians for an effective means of vaccinating deer against bTB.

Heteroresistance to cefiderocol in carbapenem-resistant in the CREDIBLE-CR study was not linked to clinical outcomes: a analysis.

The population analysis profiling (PAP) test is considered the "gold standard" method to detect heteroresistance. It exposes bacteria to increasing concentrations of antibiotics at high cell densities to detect any minority resistant subpopulations that might be missed by the low inoculums used for reference susceptibility tests. However, its clinical relevance has not been well established.

New boronate drugs and evolving NDM-mediated beta-lactam resistance.

Taniborbactam and xeruborbactam are dual serine-/metallo-beta-lactamase inhibitors (BLIs) based on a cyclic boronic acid pharmacophore that undergo clinical development. Recent report demonstrated that New Delhi metallo-beta-lactamase (NDM)-9 (differs from NDM-1 by a single amino acid substitution, E152K, evolved to overcome Zn (II) deprivation) is resistant to inhibition by taniborbactam constituting pre-existing taniborbactam resistance mechanism. Using microbiological and biochemical experiments, we show that xeruborbactam is capable of inhibiting NDM-9 and propose the structural basis for differences between two BLIs.

Determination of Disk Diffusion and MIC Quality Control Ranges for Nafithromycin (WCK 4873), a New Lactone-Ketolide.

Disk diffusion and MIC quality control (QC) ranges were determined for nafithromycin, a new lactone-ketolide, following the completion of a nine-laboratory, Clinical and Laboratory Standards Institute (CLSI) document M23-defined tier 2 study. Five QC strains consistent with the spectrum of activity of nafithromycin were tested: ATCC 25923 (disk only), ATCC 29213 (broth only), ATCC 29212 (broth only), ATCC 49619 (disk and broth), and ATCC 49247 (disk and broth). Nafithromycin disk diffusion QC ranges were determined to be 25 to 31 mm for ATCC 25923, 25 to 31 mm for ATCC 49619, and 16 to 20 mm for ATCC 49247.

Successful eculizumab treatment of recurrent postpartum atypical hemolytic uremic syndrome after kidney transplantation.

Postpartum atypical hemolytic uremic syndrome (aHUS) is a rare disorder associated with poor maternal and fetal outcomes. We describe a case of severe postpartum aHUS with recurrence in a kidney allograft after a second pregnancy. The patient had initially presented age 28 years with aHUS that developed after her first delivery.

A randomized prospective trial of the utility of rapid on-site evaluation of transbronchial needle aspirate specimens.

Background: Previous studies have suggested an increased diagnostic yield for flexible bronchoscopic transbronchial needle aspirate (TBNA) specimens from lymph nodes when using rapid on-site evaluation by cytopathology but were limited by a lack of randomization, suggesting that selection bias may have contributed to its higher reported yield with TBNA.

Objectives: The purpose of our study was to determine the effect of rapid on-site evaluation (ROSE) on the diagnostic power of TBNA.

Methods: The study is a prospective randomized controlled trial.

Primary extragastrointestinal stromal tumor of the pleura: report of a unique case with genetic confirmation.

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal neoplasms of the tubular gastrointestinal tract, usually originate in the wall of the stomach or small intestine. Most GISTs harbor oncogenic mutations in either the KIT or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinase receptor genes and show differentiation along the lines of the interstitial cells of Cajal. Rarely, GISTs arise primarily in the omentum, mesentery, or retroperitoneum, at which sites they are referred to as "extragastrointestinal stromal tumors" (EGISTs).

Purinergic modulation of synaptic input to Purkinje neurons in rat cerebellar brain slices.

Adenosine triphosphate (ATP) is a cotransmitter and an extracellular neuromodulator in nervous systems, and it influences neural circuits and synaptic strength. We have studied a stimulating effect of ATP (100 micro m) on the synaptic input of Purkinje neurons in acute cerebellar brain slices of juvenile rats (p14-19). Bath application of ATP increased the frequency of spontaneous postsynaptic currents (sPSCs) almost twofold, and increased their amplitude.

Busulfan induces activin A expression in vitro and in vivo: a possible link to venous occlusive disease.

Purpose: Hepatic venous occlusive disease is a severe side effect after administration of busulfan before hematopoietic stem cell transplantation. The syndrome is characterized by liver enlargement, fluid retention, jaundice, and weight gain. Endothelial injury has been described as the precipitating factor.

Overexpression of glutathione S-transferase A1-1 in ECV 304 cells protects against busulfan mediated G2-arrest and induces tissue factor expression.

1. The antineoplastic drug busulfan is frequently used in preconditioning regimens for bone marrow transplantation. Pharmacokinetics vary tremendously between patients due to extensive metabolism in the liver via conjugation to glutathione catalysed by glutathione S-transferase (GST) A1-1.

Cathepsin S activity is detectable in human keratinocytes and is selectively upregulated upon stimulation with interferon-gamma.

Keratinocytes are an integral component of the skin immune system and function as nonprofessional antigen-presenting cells in pathophysiologic conditions when they express major histocompatibility complex class II molecules, e.g., in psoriasis.

Synergistic effect of gentamicin plus ampicillin on enterococci with differing sensitivity to gentamicin: a phenotypic assessment of NCCLS guidelines.

Between December 1, 1993, and December 1, 1996, we tested 4,411 isolates of Enterococcus sp. at gentamicin concentrations of 500 micrograms/mL and 2000 micrograms/mL using agar dilution to phenotypically categorize them into 3 groups: those with a MIC < or = 500 micrograms/mL (n = 3,132; 71%); a MIC > 500, but < or = 2000 micrograms/mL (n = 441; 10%); and those with a MIC > 2000 micrograms/mL (n = 838; 19%). Ten unique strains of each phenotype were tested to determine which gentamicin concentration was the best in vitro predictor of synergy with ampicillin.

Highly reproducible bactericidal activity test results by using a modified National Committee for Clinical Laboratory Standards broth macrodilution technique.

Bactericidal testing historically has exhibited variable reproducibility, even when prior standardized methods were employed. Several modifications to the National Committee for Clinical Laboratory Standards (NCCLS) broth macrodilution method are proposed to improve reproducibility. Recommended changes from the approved NCCLS guidelines (M21-A and M26-A) include omitting serum supplementation of Mueller-Hinton broth, incubating tubes at 35 degrees C for 24 h with no agitation until they are sampled, running all tests in duplicate with six dilutions instead of nine, reincubating the test for an additional 24 h to resolve discrepant bactericidal activity test results, using a single 0.

Evolving clinical problems with Streptococcus pneumoniae: increasing resistance to antimicrobial agents, and failure of traditional optochin identification in Chicago, Illinois, between 1993 and 1996.

Infections due to multidrug-resistant pneumococci are a growing concern. Through December 1995, over 85% of isolates recovered from our patients in Chicago, Illinois, were fully susceptible to penicillin, and only a rare resistant strain was recovered from blood or cerebrospinal fluid (CSF). In December 1995, we began to observe bloodstream infections due to Streptococcus pneumoniae with penicillin MICs that represented either intermediate or full resistance to penicillin.

Alopecia areata but not androgenetic alopecia is characterized by a restricted and oligoclonal T-cell receptor-repertoire among infiltrating lymphocytes.

Although the etiology of alopecia areata is still unknown, evidence has accumulated to support an autoimmune pathogenesis for this disease. To evaluate the role of T cells in alopecia areata the T-cell receptor VB-repertoire was investigated in lesional skin and blood of 5 patients by means of a semiquantitative technique based on the reverse transcriptase polymerase chain reaction. Three patients with androgenetic alopecia served as controls.

Induction of psoriasiform inflammation by a bacterial superantigen in the SCID-hu xenogeneic transplantation model.

Psoriasis is a chronic skin disease affecting about 2% of the Caucasian population, characterized by co-existing inflammation and epidermal hyperproliferation. A T-lymphocyte-mediated autoimmune reaction induced by bacterial superantigens might be central in its pathogenesis. To model psoriasiform inflammation, we transplanted clinically uninvolved skin from psoriatic patients onto SCID mice.

Optimizing detection of microbial sepsis: a comparison of culture systems using packaged sets with directions for blood collection.

Detection of microbial sepsis is an important aspect of medical practice. To facilitate the recovery of bacteria and fungi we evaluated 10,933 complete blood culture sets integrating the automated ESP system (Difco) with a manual system using the Isolator (Wampole) and Thiol broth bottle (Difco). To improve compliance with the recommended procedure for submitting specimens, we packaged the three components as a unit that included brief instructional material.

T-cell-receptor repertoire in chronic plaque-stage psoriasis is restricted and lacks enrichment of superantigen-associated V beta regions.

Preferential usage of certain T-cell receptors by the lymphocytic infiltrate in psoriasis might indicate the involvement of an antigen in the pathogenesis of this disease. However, to date there are no data on the complete T-cell-receptor V alpha and V beta repertoire in psoriatic patients. We therefore compared the usage of T-cell-receptor variable regions in blood and skin of 10 patients with chronic plaque-stage psoriasis by means of semiquantitative polymerase chain reaction.

Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils.

The ability of cultured human fibroblasts to reorganize and contract three dimensional collagen I gels is regarded as an in vitro model for the reorganization of connective tissue during wound healing. We investigated whether adhesion receptors of the integrin family are involved. It was found that synthesis and transcription of the alpha 2 beta 1 integrin (but not of alpha 1 beta 1 or alpha 3 beta 1) is selectively upregulated when fibroblasts are seeded into type I collagen gels.

Predicting outcome following pulmonary resection in cystic fibrosis patients.

A small subset of cystic fibrosis (CF) patients develop pulmonary disease primarily limited to one lobe or lung segment requiring prolonged recurrent hospitalizations with intensive medical therapy. Although surgery has been advocated for patients who do not respond to medical therapy, very little is known about criteria for selection of patients who might benefit from resection of the involved parenchyma. In an attempt to further define criteria for pulmonary resection in these patients, we retrospectively reviewed our experience at Tulane Medical Center over the past 10 years.

Surgical management of children and young adults with Marfan syndrome and pectus excavatum.

Significant chest wall deformities occur in two thirds of children with Marfan syndrome (MS). The symptoms, physical findings, and surgical outcome of 11 patients with MS and severe pectus excavatum who required operative repair were reviewed. The diagnosis of MS was made before the pectus repair in six patients, at the time of evaluation of pectus in two patients, and after the repair in three patients.

Efficacy of differential mucin staining for predicting synchronous and metachronous colorectal carcinomas.

Despite the controversy regarding the significance and usefulness of histochemically differential mucin staining as a marker for colorectal neoplasms, some investigators have used this technique to help define those persons at risk for development of recurrent colorectal carcinoma. To further evaluate the efficacy of this method, we reviewed 85 surgical specimens of the colon and rectum using a high iron diamine-alcian blue staining technique. The group studied included 73 patients with synchronous or metachronous carcinomas and adenomas and 12 patients with no recurrence for more than 5 years who had undergone adequate follow-up, including physical examination; evaluation of serum chemistry findings; and colonoscopy, barium enema, or both.