Diagnostic laboratory standardization and validation of platelet transmission electron microscopy.

Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessing distinct ultrastructural abnormalities in inherited platelet disorders (IPDs). Nevertheless, PTEM remains mainly a research tool due to the lack of standardized procedures, a validated dense granule (DG) count reference range, and standardized image interpretation criteria. The aim of this study was to standardize and validate PTEM as a clinical laboratory test.

Comprehensive Platelet Phenotypic Laboratory Testing and Bleeding History Scoring for Diagnosis of Suspected Hereditary Platelet Disorders: A Single-Institution Experience.

Objectives: Patients with hereditary/congenital platelet disorders (HPDs) have a broad range of clinical manifestations and laboratory phenotypes. We assessed the performance characteristics of the International Society on Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT) and clinically validated platelet laboratory tests for diagnosis of HPDs.

Methods: The records of 61 patients with suspected HPDs were reviewed and ISTH-BAT scores calculated.

Practice patterns in the diagnosis of inherited platelet disorders within a single institution.

: The diagnosis of inherited platelet disorders (IPDs) is challenging with variable diagnostic practices existing between institutions. To determine patterns and utility of diagnostic testing practices for IPDs within a single institution, a retrospective cohort study was performed. Records of 50 patients (50% women), median age 32 years (1 day to 81 years) were analyzed.

Role of the cochaperone Tpr2 in Hsp90 chaperoning.

The molecular chaperones Hsp90 and Hsp70 are highly regulated by various cochaperones that participate in the activation of steroid receptors. Here we study Tpr2 (also called DjC7), a TPR domain-containing type III J protein implicated in steroid receptor chaperoning. We propose that Tpr2 plays a role in the Hsp90-dependent chaperoning of the progesterone receptor (PR).

Reactive oxygen species and human platelet GP IIb/IIIa receptor activation.

This study concerned reactive oxygen species for their potential to activate human platelet GP IIb/IIIa receptors. All cells produce reactive oxygen species - radicals that can abstract electrons and hydrogen atoms from biological molecules to alter cell function. In many cells, radicals contribute to cellular signaling.

A phase II study of ABT-510 (thrombospondin-1 analog) for the treatment of metastatic melanoma.

Objectives: Thrombospondins are natural inhibitors of angiogenesis, tumor metastases, and tumor growth (melanoma). ABT-510 is a synthetic analog of thrombospondin-1, well tolerated in phase I studies. We conducted a phase II trial evaluating the clinical efficacy of ABT-510 and its effects on biomarkers of angiogenesis and immunity in patients with metastatic melanoma (MM).

Mitochondrial injury and caspase activation by the local anesthetic lidocaine.

Background: Lidocaine, a local anesthetic, can be neurotoxic. However, the cellular mechanisms of its neurotoxicity at concentrations encountered during spinal anesthesia remain unclear.

Methods: The authors examined the mechanisms of lidocaine neurotoxicity in the ND7 cell line derived from rat dorsal root ganglion.

Effect of local anesthetic on neuronal cytoplasmic calcium and plasma membrane lysis (necrosis) in a cell culture model.

Background: To investigate the mechanism by which rare cases of spinal local anesthetic (LA) neurotoxicity occur, we have tested the hypotheses that LAs elevate cytoplasmic calcium (Ca2+(cyt)), that this is associated with a neurotoxic effect, and that lidocaine and bupivacaine differ in their neurotoxicity.

Methods: Neurons of the ND7 cell culture line, derived from dorsal root ganglion, were loaded with fura-2 and analyzed by digitized video fluorescence microscopy during 60 min LA exposure, allowing determination of Ca2+(cyt) and time of necrotic cell death (plasma membrane lysis) at the single neuron level.

Results: Lidocaine 0.