The three-substituted indolinone cyclin-dependent kinase 2 inhibitor 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516) kills human leukemia cells via down-regulation of Mcl-1 through a transcriptional mechanism.

Mechanisms of lethality of the three-substituted indolinone and putatively selective cyclin-dependent kinase (CDK)2 inhibitor 3-[1-(3H-imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516) were examined in human leukemia cells. Exposure of U937 and other leukemia cells to SU9516 concentrations > or =5 microM rapidly (i.e.

Thrombin generation time is a novel parameter for monitoring enoxaparin therapy in patients with end-stage renal disease.

Background: Patients with end-stage renal disease (ESRD) who receive enoxaparin are at increased risk for adverse bleeding episodes. This phenomenon appears to occur despite judicious monitoring of antifactor Xa (aFXa) activity. Better monitoring parameters are needed to quantify the anticoagulant effects of enoxaparin in the ESRD population.

Potentiation of the lethality of the histone deacetylase inhibitor LAQ824 by the cyclin-dependent kinase inhibitor roscovitine in human leukemia cells.

Interactions between the novel histone deacetylase inhibitor LAQ824 and the cyclin-dependent kinase inhibitor roscovitine were examined in human leukemia cells. Pretreatment (24 hours) with a subtoxic concentration of LAQ824 (30 nmol/L) followed by a minimally toxic concentration of roscovitine (10 micromol/L; 24 hours) resulted in greater than additive effects on apoptosis in U937, Jurkat, and HL-60 human leukemia cells and blasts from three patients with acute myelogenous leukemia. These events were associated with enhanced conformational changes in Bax; mitochondrial release of cytochrome c, Smac/DIABLO, and apoptosis-inducing factor; and a marked increase in caspase activation.

Scapular muscle tests in subjects with shoulder pain and functional loss: reliability and construct validity.

Background And Purpose: Scapular muscle performance evaluated with a handheld dynamometer (HHD) has been investigated only in people without shoulder dysfunction for test-retest reliability of data obtained with a single scapular muscle test. The purpose of this study was to assess the reliability, error, and validity of data obtained with an HHD for 4 scapular muscle tests in subjects with shoulder pain and functional loss.

Subjects And Methods: Subjects (N=40) with shoulder pain and functional loss were tested by measuring the kilograms applied with an HHD during 3 trials for muscle tests for the lower trapezius, upper trapezius, middle trapezius, and serratus anterior muscles.

Abdominal imaging features of HELLP syndrome: a 10-year retrospective review.

Objective: The purpose of this study was to describe the abdominal imaging features associated with HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, a complication of pregnancy.

Conclusion: The abdominal imaging features of HELLP syndrome include intraparenchymal and perihepatic hematomas and hemoperitoneum as noted on sonography, CT, and angiography.

Darbepoetin alfa therapeutic interchange protocol for anemia in dialysis.

Background: Erythropoiesis-stimulating proteins, such as erythropoietin alfa and darbepoetin alfa, have positively impacted anemia management. These medications improve patient outcomes and quality of life. Their costs, however, remain a major barrier for health systems.

Synergistic antileukemic interactions between 2-medroxyestradiol (2-ME) and histone deacetylase inhibitors involve Akt down-regulation and oxidative stress.

Interactions between the endogenous estradiol metabolite 2-medroxyestradiol (2-ME) and histone deacetylase inhibitors (HDACIs) have been investigated in human leukemia cells. Coadministration of subtoxic or marginally toxic concentrations of 2-ME and SAHA or sodium butyrate in diverse human leukemia-cell types resulted in a marked increase in oxidative damage (eg, generation of reactive oxygen species [ROSs]), mitochondrial injury (eg, cytochrome c release and Bax translocation), caspase activation, and apoptosis. These interactions were also noted in primary human leukemia cells but not in normal bone marrow CD34+ cells.

Laparoscopic adjustable gastric banding: evolving clinical experience.

Laparoscopic adjustable gastric banding (LAGB) was first introduced in the early 1990s as a potentially safe, controllable, and reversible method for achieving significant weight loss in the severely obese. It is timely to review the existing data on this procedure derived from European, Australian, and American studies and compare and contrast their results. Special emphasis is placed on clinical outcomes and reported complications of LAGB.

The farnesyltransferase inhibitor L744832 potentiates UCN-01-induced apoptosis in human multiple myeloma cells.

Purpose: The purpose of this study was to characterize interactions between the farnesyltransferase inhibitor L744832 and the checkpoint abrogator UCN-01 in drug-sensitive and drug-resistant human myeloma cell lines and primary CD138+ multiple myeloma cells.

Experimental Design: Wild-type and drug-resistant myeloma cell lines were exposed to UCN-01 +/- L744832 for 24 hours, after which mitochondrial injury, caspase activation, apoptosis, and various perturbations in signaling and survival pathways were monitored.

Results: Simultaneous exposure of myeloma cells to marginally toxic concentrations of L744832 and UCN-01 resulted in a synergistic induction of mitochondrial damage, caspase activation, and apoptosis, associated with activation of p34cdc2 and c-Jun-NH2-kinase and inactivation of extracellular signal-regulated kinase, Akt, GSK-3, p70(S6K), and signal transducers and activators of transcription 3 (STAT3).

A hypothesis-generating study to evaluate platelet activity in diabetics with chronic kidney disease.

BACKGROUND: It is well described that diabetes mellitus is a hypercoagulable state. It is also known that patients with renal dysfunction have impaired platelet aggregation and function. It is not well described how renal dysfunction affects the hypercoagulability associated with diabetes.

2-Methoxyestradiol-induced apoptosis in human leukemia cells proceeds through a reactive oxygen species and Akt-dependent process.

The effects of 2-Methoxyestradiol (2ME)-induced apoptosis was examined in human leukemia cells (U937 and Jurkat) in relation to mitochondrial injury, oxidative damage, and perturbations in signaling pathways. 2ME induced apoptosis in these cells in a dose-dependent manner associated with release of mitochondrial proteins (cytochrome c, AIF), generation of reactive oxygen species (ROS), downregulation of Mcl-1 and XIAP, and inactivation (dephosphorylation) of Akt accompanied by activation of JNK. In these cells, enforced activation of Akt by a constitutively active myristolated Akt construct prevented 2ME-mediated mitochondrial injury, XIAP and Mcl-1 downregulation, JNK activation, and apoptosis, but not ROS generation.

Intramuscular angiomatous tumors associated with periosteal changes and pain.

This case report discusses two cases in which patients present with the uncommon triad of extremity pain, focal periosteal reaction on imaging studies, and intramuscular hemangioma on pathologic examination. Both patients presented in this article were older than those previously reported in the literature. Neither patient reported complete resolution of pain following excision, although there was marked improvement.

The small-molecule Bcl-2 inhibitor HA14-1 interacts synergistically with flavopiridol to induce mitochondrial injury and apoptosis in human myeloma cells through a free radical-dependent and Jun NH2-terminal kinase-dependent mechanism.

Interactions between the cyclin-dependent kinase inhibitor flavopiridol and the small-molecule Bcl-2 antagonist HA14-1 were examined in human multiple myeloma cells. Whereas individual treatment of U266 myeloma cells with 10 micromol/L HA14-1 or 100 nmol/L flavopiridol had little effect, exposure of cells to flavopiridol (6 hours) followed by HA14-1 (18 hours) resulted in a striking increase in mitochondrial dysfunction (cytochrome c and Smac/DIABLO release; loss of mitochondrial membrane potential), activation of the caspase cascade, apoptosis, and diminished clonogenic survival. Similar findings were noted in other myeloma cell lines (e.

Farnesyltransferase inhibitors interact synergistically with the Chk1 inhibitor UCN-01 to induce apoptosis in human leukemia cells through interruption of both Akt and MEK/ERK pathways and activation of SEK1/JNK.

Interactions between the Chk1 inhibitor UCN-01 and the farnesyltransferase inhibitor L744832 were examined in human leukemia cells. Combined exposure of U937 cells to subtoxic concentrations of UCN-01 and L744832 resulted in a dramatic increase in mitochondrial dysfunction, apoptosis, and loss of clonogenicity. Similar interactions were noted in other leukemia cells (HL-60, Raji, Jurkat) and primary acute myeloid leukemia (AML) blasts.

Fiberoptic assessment of laryngeal mask airway placement: blind insertion versus direct visual epiglottoscopy.

Purpose: The study aims to compare the frequency of ideal anatomic placement of the laryngeal mask airway (LMA) using the traditional blind insertion approach with one where placement was facilitated by the use of a laryngoscope (epiglottoscopy).

Patients And Methods: A prospective comparison of 132 patients divided into 2 groups (38 with the blind technique and 94 with the direct technique) were evaluated with 2 airway assessment methods, Wilson and Mallampati. We also considered whether there was a relationship between these criteria and the successful placement into an ideal position.

The adolescent varicocele: to treat or not to treat.

Whether to treat adolescents with varicocele is controversial because over 80% of adult varicoceles are not associated with infertility. Most physicians agree that treating all adolescents with varicocele and subjecting boys to unnecessary surgery is inappropriate,costly, and not without ethical considerations. Waiting until patients present as adults with potentially irreversible infertility, however, is equally unacceptable.

Platelet transfusions during coronary artery bypass graft surgery are associated with serious adverse outcomes.

Background: Platelet (PLT) transfusions are administered in cardiac surgery to prevent or treat bleeding, despite appreciation of the risks of blood component transfusion. The current analysis investigates the hypothesis that PLT transfusion is associated with adverse outcomes associated with coronary artery bypass graft surgery (CABG).

Study Design And Methods: Data originally collected during double-blind placebo-controlled phase III trials for licensure of Trasylol (aprotinin injection) were retrospectively analyzed.

Enhanced anticoagulant activity of enoxaparin in patients with ESRD as measured by thrombin generation time.

Background: Patients with renal dysfunction who undergo systemic anticoagulation with enoxaparin are at increased risk for bleeding. Although there is decreased renal clearance of enoxaparin in this population, the clinical utility of monitoring antifactor Xa activity is controversial because it is weakly correlated to bleeding. The goal of this study was to investigate the role of other novel anticoagulation markers, such as thrombin generation time, platelet contractile force, and clot elastic modulus, while controlling for antifactor Xa activity in patients with and without renal dysfunction.

Bryostatin 1/ionomycin (B/I) ex vivo stimulation preferentially activates L-selectinlow tumor-sensitized lymphocytes.

We have shown that tumor vaccine-sensitized draining lymph node (vDLN) cells activated ex vivo with bryostatin and ionomycin (B/I) were capable of inducing antigen-specific regression of a murine mammary tumor, 4T07. vDLN cells not activated with B/I were ineffective. We hypothesized that B/I selectively activates tumor-sensitized (CD62Llow) lymphocytes, to account for the highly potent and tumor-specific activity.

Contribution of disruption of the nuclear factor-kappaB pathway to induction of apoptosis in human leukemia cells by histone deacetylase inhibitors and flavopiridol.

Interactions between the cyclin-dependent kinase inhibitor flavopiridol and the histone deacetylase inhibitors (HDACIs) sodium butyrate (NaB) and suberoylanilide hydroxamic acid (SAHA) have been examined in human leukemia cells in relation to effects on nuclear factor kappaB (NF-kappaB) activation. Exposure (24 h) of U937 human leukemia cells to NaB (1 mM) or SAHA (1.5 microM) resulted in a marked increase in NF-kappaB DNA binding, effects that were essentially abrogated by coadministration of flavopiridol (100 nM).

Neuropsychologists diagnose traumatic brain injury.

The case of John versus Im (2002) stands for the proposition that clinical neuropsychologists are not qualified to diagnose traumatic brain injury. This ruling by the Supreme Court of Virginia prohibits neuropsychologists from testifying about these professional conclusions in the courtroom. However, in clinical practice neuropsychologists are often asked to disentangle the relative contribution of brain dysfunction and psychological factors to presenting symptomology.

A Bcr/Abl-independent, Lyn-dependent form of imatinib mesylate (STI-571) resistance is associated with altered expression of Bcl-2.

The relationship between the Src kinase Lyn and Bcl-2 expression was examined in chronic myelogenous leukemia cells (K562 and LAMA84) displaying a Bcr/Abl-independent form of imatinib mesylate resistance. K562-R and LAMA-R cells that were markedly resistant to induction of mitochondrial dysfunction (e.g.