Down-modulation of neutrophil production by erythropoietin in human hematopoietic clones

In clonogenic assays of hematopoietic progenitors, high concentrations (4 U/mL) of erythropoietin (epo) reduced the formation of granulocyte- macrophage (GM) colonies and diminished the number of granulocytes formed per culture plate. Fetal progenitors were more sensitive to these effects of epo than were progenitors from adults, displaying these reductions at greater than or equal to 1 U epo/mL. The mechanism was investigated by growing fetal progenitors stimulated by recombinant GM-CSF, in the absence of epo, and when eight-cell clones first appeared, mapping their location, then adding epo, and assessing its effect on the subsequent differentiation of the clones. In the absence of epo, the clones developed exclusively into GM colonies. However, if developing clones were presented with epo, 85% matured into GM colonies, but 15% became multilineage or normoblast colonies. In addition, developing clones that were presented with epo produced colonies that contained fewer neutrophils. These effects of epo on neutrophil generation were observed with each of three varieties of recombinant epo, and also with purified human epo, but were not observed using epo that had been neutralized with rabbit anti-epo antiserum.     

Changes in serum serotonin levels in patients with acute coronary syndrome and stable angina undergoing percutaneous coronary intervention

ObjectiveActivated platelets release serotonin, causing platelet aggregation and vasoconstriction. Serotonin levels were investigated in patients with acute coronary syndrome (ACS) and chronic stable angina (CSA) treated with percutaneous coronary intervention (PCI).MethodsConsecutive patients undergoing PCI for either ACS or CSA were enrolled between July 2009 and April 2010. Patients were pre-treated with dual antiplatelet agents (aspirin and clopidogrel) before PCI. Serum serotonin levels, measured at baseline, pre- and post-PCI, and at 90 min, and 6, 12, 24 and 48 h following PCI, were compared between ACS and CSA groups.ResultsSixty-three patients with ACS and 60 with CSA were included. Overall baseline characteristics were similar between the two groups. Serotonin levels at post-PCI (55.2 ± 120.0 versus 20.1 ± 24.0) and at peak (regardless of timepoint; 94.0 ± 170.9 versus 38.8 ± 72.3) were significantly higher in the ACS versus CSA group. At 90 min and 6, 24 and 48 h post-PCI, serum serotonin was numerically, but not significantly, higher in patients with ACS. Serotonin levels fluctuated in both groups, showing an initial rise and fall, rebound at 24 h and drop at 48 h post-PCI.ConclusionsIn patients undergoing PCI, serum serotonin was more elevated in patients with ACS than those with CSA, suggesting the need for more potent and sustained platelet inhibition, particularly in patients with ACS.     

Health‐related quality of life among migrant workers: The impact of health‐promoting behaviors

Health‐related quality of life is an important aspect of migrant workers' overall well‐being and adaptation. The aims of this study were to develop a structural model and test the health‐related quality of life among migrant workers. A cross‐sectional study design was used, and data were collected from 228 migrant workers from China who are currently living in Korea and using the services of free clinics for health issues. The structured questionnaire disseminated for the study was designed to measure health‐related quality of life, health‐promotion behaviors, barriers, resources, and perceptual factors. Structural equation modeling was used to test the hypotheses. Health‐promotion behaviors and self‐efficacy have significant positive direct effects on health‐related quality of life, and acculturative stress has a significant negative direct effect on health‐related quality of life. These findings suggest that certain strategies are needed for developing health‐promotion programs aimed at the betterment of migrant workers' health‐related quality of life. Specifically, health‐promotion behaviors and self‐efficacy among migrant workers should be encouraged, and strategies for decreasing their acculturative stress should be formulated.     

Multiple sclerosis: serial study of gadolinium-enhanced MR imaging

Thirteen patients with definite multiple sclerosis (MS), studied 16-24 months previously with magnetic resonance (MR) imaging with and without enhancement by intravenously administered gadolinium diethylenetriaminepentaacetic acid (DTPA) dimeglumine, were reexamined with a similar protocol. Assessment of enhancement and clinical activity in both studies revealed that enhancement was observed in 13 of 14 cases in which clinical activity had changed within 4 weeks of the study and thus appeared more sensitive than clinical examination in determining active disease. The 3-minute postinjection, short repetition time image (TR) was the most efficient for depicting enhancement. Enhancing lesions (active plaques) arose from previously hyper- or isointense regions on long TR images. Previously active lesions reverted to areas of iso- or hyperintensity on long TR images. Serial comparison of long TR images in this population reveals a decrease in high-intensity lesions on long TR images in some cases and an increase in others. The findings of high-intensity regions on long TR images and previously enhancing lesions both becoming isointense suggests that transient inflammatory changes with concomitant edema without demyelination and/or with significant remyelination may occur in some MS lesions. MS lesions are dynamic; both active and inactive lesions may show dramatic change on longitudinal MR imaging studies.     

Contrasting effects of recombinant human granulocyte-macrophage colony- stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia

Recombinant human granulocyte colony-stimulating factor (G-CSF) treatment has been shown to increase average neutrophil counts substantially in patients with childhood-onset cyclic neutropenia (or "cyclic hematopoiesis"), but not to eliminate the cyclic oscillations of neutrophil counts or those of other blood elements (monocytes, platelets, eosinophils, and reticulocytes) that are characteristic of this hematopoietic disorder. Indeed, oscillations of neutrophil counts are amplified during G-CSF treatment. We have compared the effects of recombinant granulocyte-macrophage-CSF (GM-CSF) with those of G-CSF in three patients with this disease (2 men and 1 woman, 17, 30, and 32 years of age). These patients were treated with GM-CSF (2.1 micrograms/kg/day, subcutaneously) for 6 weeks, preceded and followed by 6 to 13 weeks of detailed observation to document changes in the cyclic oscillations of blood neutrophils and other blood elements; two of the patients were subsequently treated with G-CSF (5.0 micrograms/kg/d, subcutaneously) and observed for comparable periods of time. Unlike G-CSF treatment, which increased average neutrophil counts more than 20-fold, GM-CSF increased neutrophil counts only modestly, from 1.6- to 3.9-fold, although eosinophilia of varying prominence was induced in each patient. However, at the same time, GM-CSF treatment dampened or eliminated the multilineage oscillations of circulating blood elements (neutrophils, monocytes, platelets, and/or reticulocytes) in each of the patients. In contrast, G-CSF treatment of the same patients markedly amplified the oscillations of neutrophil counts and caused the cycling of other blood elements (monocytes in particular) to become more distinct. These findings support the conclusion that the distinctive cycling of blood cell production in childhood-onset cyclic neutropenia results from abnormalities in the coordinate regulation of both GM-CSF-responsive, multipotential progenitor cells and G-CSF-responsive, lineage-restricted, neutrophil progenitors.     

Defects in neurofibromatosis 2 protein function can arise at multiple levels

Neurofibromatosis 2 (NF2) is an inherited cancer syndrome resulting from mutations in the NF2 tumor suppressor gene. Analysis of NF2 mutations has revealed some general genotype-phenotype correlations. Severe disease has been associated with mutations that produce a premature termination while more mild disease has been associated with missense mutations. Here, we provide experimental proof for these genotype-phenotype correlations by demonstrating that nonsense mutations fail to produce stable merlin protein while missense mutations result in the generation of merlin proteins defective in negative growth regulation. This inability to suppress cell growth may result from defects in the function of merlin at several levels, including failure to form an intramolecular complex. Based on these findings, we propose a model for merlin growth suppression that provides a framework for analyzing NF2 patient mutations and merlin function.      

Limitation of Conventional Audiometry in Identifying Hidden Hearing Loss in Acute Noise Exposure

PurposeThe concept of hidden hearing loss can explain the discrepancy between a listener''s perception of hearing ability and hearing evaluation using pure tone audiograms. This study investigated the utility of the suprathreshold auditory brainstem response (ABR) for the evaluation of hidden hearing loss in noise-exposed ear with normal audiograms.Materials and MethodsA total of 15 patients (24 ears) with normal auditory thresholds and normal distortion product otoacoustic emissions were included in a retrospective analysis of medical records of 80 patients presenting with histories of acute noise exposure. The control group included 12 subjects (24 ears) with normal audiograms and no history of noise exposure. Pure tone audiometry and suprathreshold ABR testing at 90 dB peSPL were performed. The amplitudes and latencies of ABR waves I and V were compared between the noise-exposed and control groups.ResultsWe found no significant difference in the wave I or V amplitude, or the wave I/V ratio, between the two groups. The latencies of ABR wave I, V, and I-V interpeak interval were compared, and no significant intergroup difference was observed.ConclusionThe results suggest that either hidden hearing loss may not be significant in this cohort of patients with acute noise exposure history, or the possible damage by noise exposure is not reflected in the ABRs. Further studies are needed to inquire about the role of ABR in identification of hidden hearing loss.