Citations

Recently the World Health Organization (WHO), in collaboration with the European Association for Haematopathology and the Society for Hematopathology, published a revised and updated edition of the WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissues. The 4th edition of the WHO classification incorporates new information that has emerged from scientific and clinical studies in the interval since the publication of the 3rd edition in 2001, and includes new criteria for the recognition of some previously described neoplasms as well as clarification and refinement of the defining criteria for others. It also adds entities—some defined principally by genetic features—that have only recently been characterized. In this paper, the classification of myeloid neoplasms and acute leukemia is highlighted with the aim of familiarizing hematologists, clinical scientists, and hematopathologists not only with the major changes in the classification but also with the rationale for those changes.

Membranes flex with changes in transmembrane potential as a result of changes in interfacial tension, the Lippman effect. We studied the membrane electromotility of Shaker K + -transfected HEK-293 cells in real time by using combined patch-clamp atomic force microscopy. In the voltage range where the channels were closed, Shaker expression had little effect on electromotility relative to wild-type cells. Depolarization between −120 and −40 mV resulted in a linear upward cantilever deflection equivalent to an increase in membrane tension. However, when depolarized sufficiently for channel opening, the electromotility saturated and only recovered over 10 s of milliseconds. This remarkable loss of motility was associated with channel opening, not ionic flux or movement of the voltage sensors. The IL mutant of Shaker , in which the voltage dependence of channel opening but not sensor movement is shifted to more positive potentials, caused the loss of electromotility saturation also to shift to more positive potentials. The temporary loss of electromotility associated with channel opening is probably caused by local buckling of the bilayer as the inner half of the channel expands as expected from X-ray structural data.

The molecular mechanism of autocrine regulation of vascular endothelial growth factor (VEGF) in chronic lymphocytic leukemia (CLL) B cells is unknown. Here, we report that CLL B cells express constitutive levels of HIF-1α under normoxia. We have examined the status of the von Hippel-Lindau gene product (pVHL) that is responsible for HIF-1α degradation and found it to be at a notably low level in CLL B cells compared with normal B cells. We demonstrate that the microRNA, miR-92-1, overexpressed in CLL B cells, can target the VHL transcript to repress its expression. We found that the stabilized HIF-1α can form an active complex with the transcriptional coactivator p300 and phosphorylated-STAT3 at the VEGF promoter and recruit RNA polymerase II. This is initial evidence that pVHL, without any genetic alteration, can be regulated by microRNA and explains the aberrant autocrine VEGF secretion in CLL.

Background and Purpose— Epidemiological studies have found strong correlations between elevated plasma fibrinogen levels and both ischemic stroke incidence and stroke mortality. Little is known about the influence of fibrinogen levels on functional stroke outcome. Methods— Placebo data from the Stroke Treatment with Ancrod Trial (STAT) and European Stroke Treatment with Ancrod Trial (ESTAT) were analyzed. Fibrinogen levels were determined within 3 hours (STAT) or 6 hours (ESTAT) of stroke onset and at preset intervals throughout 5 days of intravenous infusions. Barthel Index scores at 90 days quantified functional outcomes. The association between initial fibrinogen levels and functional outcomes was evaluated using a multiple logistic regression analysis. Results— Fibrinogen levels increased gradually over the first 24 hours from a pretreatment median value of 340 mg/dL to a 24-hour median value of 376 mg/dL. In a univariate analysis, the proportion of patients with good functional outcome decreased with increasing quartiles of initial fibrinogen levels in both STAT (36.0% to 26.2%) and ESTAT (53.8% to 24.8%). In a multifactorial analysis, the same trend was observed. Patients with initial fibrinogen levels <450 mg/dL had better outcomes in both studies; the difference (42.0% versus 21.6%) was significant in ESTAT ( P =0.0006), even when corrected for age and initial stroke severity. Conclusion— The independent association of higher initial fibrinogen levels with poor outcome needs to be verified using a larger acute stroke dataset. Even in the present small populations, the apparent association of these 2 variables suggests that treatments designed to reduce fibrinogen levels could potentially be important in treating acute ischemic stroke.

Background— The incidence and significance of gasping after cardiac arrest in humans are controversial. Methods and Results— Two approaches were used. The first was a retrospective analysis of consecutive confirmed out-of-hospital cardiac arrests from the Phoenix Fire Department Regional Dispatch Center text files to determine the presence of gasping soon after collapse. The second was a retrospective analysis of 1218 patients with out-of-hospital cardiac arrests in Arizona documented by emergency medical system (EMS) first-care reports to determine the incidence of gasping after arrest in relation to the various EMS arrival times. The primary outcome measure was survival to hospital discharge. An analysis of the Phoenix Fire Department Regional Dispatch Center records of witnessed and unwitnessed out-of-hospital cardiac arrests with attempted resuscitation found that 44 of 113 (39%) of all arrested patients had gasping. An analysis of 1218 EMS-attended, witnessed, out-of-hospital cardiac arrests demonstrated that the presence or absence of gasping correlated with EMS arrival time. Gasping was present in 39 of 119 patients (33%) who arrested after EMS arrival, in 73 of 363 (20%) when EMS arrival was <7 minutes, in 50 of 360 (14%) when EMS arrival time was 7 to 9 minutes, and in 25 of 338 (7%) when EMS arrival time was >9 minutes. Survival to hospital discharge occurred in 54 of 191 patients (28%) who gasped and in 80 of 1027 (8%) who did not (adjusted odds ratio, 3.4; 95% confidence interval, 2.2 to 5.2). Among the 481 patients who received bystander cardiopulmonary resuscitation, survival to hospital discharge occurred among 30 of 77 patients who gasped (39%) versus only 38 of 404 among those who did not gasp (9%) (adjusted odds ratio, 5.1; 95% confidence interval, 2.7 to 9.4). Conclusions— Gasping or abnormal breathing is common after cardiac arrest but decreases rapidly with time. Gasping is associated with increased survival. These results suggest that the recognition and importance of gasping should be taught to bystanders and emergency medical dispatchers so as not to dissuade them from initiating prompt resuscitation efforts when appropriate.

This cross-sectional study examines the relationship between parenting stress and concerns identified by developmental screening and their effects on parents' decisions to seek medical care for their children. A total of 182 parents completed both the Parenting Stress Index (PSI) and the Parents' Evaluation of Developmental Status (PEDS) when their children were admitted to a sick child care program that provides parents the option of requesting medical evaluations for their children with mild acute illnesses. Although 31.6% of parents (N = 62) requested medical evaluations, neither PSI nor PEDS scores were associated with these requests. However, PEDS scores indicating significant parental concerns about their child's development or behavior predicted clinically significant levels of parenting stress on the PSI (odds ratio 4.9; 95% confidence interval, 1.5-15.9; P = .007). Primary pediatric health care providers who routinely perform developmental screening need to consider this relationship when interpreting developmental screening results and offer supportive and referral services to families as needed.