Modulation of P2 auditory-evoked responses by the spectral complexity of musical sounds

We investigated whether N1 and P2 auditory-evoked responses are modulated by the spectral complexity of musical sounds in pianists and non-musicians. Study participants were presented with three variants of a C4 piano tone equated for temporal envelope but differing in the number of harmonics contained in the stimulus. A fourth tone was a pure tone matched to the fundamental frequency of the piano tones. A simultaneous electroencephalographic/magnetoencephalographic recording was made. P2 amplitude was larger in musicians and increased with spectral complexity preferentially in this group, but N1 did not. The results suggest that P2 reflects the specific features of acoustic stimuli experienced during musical practice and point to functional differences in P2 and N1 that relate to their underlying mechanisms.     

p130Rb2 and p27kip1 cooperate to control mobilization of angiogenic progenitors from the bone marrow

Neoangiogenesis involves both bone marrow-derived myelomonocytic and endothelial progenitor cells as well as endothelial cells coopted from surrounding vessels. Cytokines induce these cells to proliferate, migrate, and exit the cell cycle to establish the vasculature; however, which cell cycle regulators play a role in these processes is largely unknown. Here, we report that mice lacking the cell cycle inhibitors p130 and p27 show defects in tumor neoangiogenesis, both in xenografts and spontaneously arising tumors. This defect is associated with impaired mobilization of endothelial and myelomonocytic angiogenic progenitors from the bone marrow. This article documents the role of these molecules in angiogenesis and further suggests that cell expansion and mobilization from the bone marrow of angiogenic precursors are separable events.     

Treatment of hemorrhagic lymphatic malformation of the tongue with a pulsed-dye laser

Hemorrhagic lymphatic malformation (formerly called hemolymphangioma) of the tongue is an uncommon malformation that may pose both functional and cosmetic problems for the patient. The challenge has been to find a conservative treatment with low morbidity and better results than those achieved with surgical excision, which has been the mainstay of therapy. We report a case of successful treatment of a hemorrhagic lymphatic malformation of the tongue with a variable-pulse 595-nm pulsed-dye laser (Vbeam; Candela Corp, Wayland, Mass). In this patient, pulsed-dye laser treatment of the hemorrhagic lymphatic malformation achieved satisfactory functional and cosmetic outcomes. Its use in superficial vascular lesions of the mucosa should be considered.     

Developing a maternity unit visiting policy

Southern Derbyshire Acute Hospitals NHS Trust has a policy of open visiting for people who wish to visit ward-based patients. The maternity unit, however, has adopted a slightly different approach, in which the visiting policy loosely consists of set hours with a degree of flexibility for mothers and visitors who wish to have extended visiting or want visitors outside the set hours. This article describes research undertaken to formulate a policy within the trust.     

Tumor necrosis factor alpha-stimulated endothelium: an inducer of dendritic cell development from hematopoietic progenitors and myeloid leukemic cells

Especially when exposed to inflammatory stimuli, endothelial cells (EC) have been shown to promote the maturation of monocytes into dendritic cells (DC) and the long-term proliferation of CD34+ cells by constitutive cytokine production and direct cellular contact. We therefore hypothesized that cytokine-stimulated EC would induce hematopoietic progenitor cells to develop into mature dendritic cells. To test this theory, human CD34+ cells derived from cord blood or leukapheresis products were cultured with a monolayer of either interleukin (IL)-1beta, IL-4, or tumor necrosis factor (TNF)-alpha-stimulated human umbilical cord EC. The cells in suspension were analyzed weekly over a period of 6 weeks. IL-1beta supported cell expansion, whereas IL-4 had no effect on cell expansion or DC differentiation. Only TNF-alpha-stimulated EC induced the development of mature, allostimulatory DC with a high expression of CD83, HLA-DR, CD1a, and costimulatory molecules like CD80 and CD86. Acute myeloid leukemia cells from the cell line Kasumi-1 also developed DC-like features when cocultured with TNF-alpha-stimulated EC. Direct contact between endothelial and progenitor cells increased the number of developing DC. Cell cycle analysis and apoptosis studies demonstrated a reduced G2M fraction, an increased S fraction, and a decrease in TNF-alpha-dependent apoptosis of DC developing in the presence of endothelial cells. As shown by electron and confocal microscopic studies, intimate interactions between EC and DC occurred, resulting in the internalization of the developing DC within the EC monolayer and a bidirectional exchange of proteins. We conclude that, via the action of TNF-alpha, inflamed human endothelium can induce CD34+ and leukemic cells to differentiate into dendritic cells.     

Patterns of uveitis in a tertiary eye care center in Iran

PURPOSE: To identify the distribution and characteristics of new uveitis referrals to a tertiary eye care center in Tehran. METHODS: A three-year prospective study was carried out to obtain information on 544 new patients referred with uveitis. A complete ophthalmologic examination was performed in all cases; a routine set of tests and an additional battery of directed workup were conducted when indicated. RESULTS: Mean age was 32.3 years. There was no significant sex predominance. The most common forms of uveitis were anterior (38.4%) vs. other anatomical forms, chronic (62.1%) vs. acute (28.3%), nongranulomatous (85.5%) vs. granulomatous (14.5%), and noninfectious (83.5%) vs. infectious (16.5%). With regard to etiology, 45.5% were idiopathic, 19.9% were due to specific ocular disease, and 37.3% were associated with systemic disorders. Behcet's disease was the most common noninfectious disease and toxoplasmosis the most common infectious entity. The most prevalent causes were idiopathic, Fuchs' heterochromic iridocylitis, and seronegative spondyloarthropathies in anterior uveitis; toxoplasmosis, Eales disease, and toxocariasis in posterior uveitis; idiopathic, sarcoidosis, and multiple sclerosis in intermediate uveitis; and, finally, Behcet's disease, idiopathic, and Vogt-Koyanagi-Harada syndrome in panuveitis. The most frequent cause in patients under 16 years of age was pars planitis. Over 80% of the patients belonged to middle-to-upper socioeconomic classes. Uveitis significantly affected patients' lives in 63.1% of the cases. CONCLUSION: Although the current study was performed at a referral center, it may reflect to some extent the different distribution of uveitis in Iran and probably other Middle Eastern countries. Some entities such as presumed ocular histoplasmosis were not found, cytomegalovirus retinitis and birdshot chorioretinopathy were extremely rare, and HLA-B27-associated iridocyclitis was less commonly observed. In contrast, Behcet's disease, Fuchs' heterochromic iridocyclitis, Eales disease, and toxocariasis were among the more prevalent entities.     

s-thalidomide has a greater effect on apoptosis than angiogenesis in a multiple myeloma cell line

s-Thalidomide has proven efficacy in multiple myeloma. Although it has both antiangiogenic and pro-apoptotic effects, its primary mode of therapeutic action remains unclear. We have investigated the changes to the expression of genes involved with these cellular processes following culture with s-thalidomide in the U266 MM cell line. Cells were cultured with s-thalidomide (0-1000 microM), and cell parameters, including apoptosis, were assessed on day 3. RNA was extracted from cells cultured for 24 h at the IC(50) concentration of s-thalidomide, and changes to gene expression were investigated by microarray methodologies. A reduction in cell viability was observed in U266 cells cultured with s-thalidomide (IC(50): 362 microM), which were mirrored by significant increases in apoptosis (for example, 200 microM on day 3: 40.3+/-3.1% vs. 3.2+/-0.4% on day 0; P<0.001). There were changes in the expression profile of genes involved in angiogenesis and apoptosis, but the changes were most dramatic in the apoptotic genes. In particular, the expression of I-kappaB kinase was decreased by two-fold, which was associated with a four-fold decrease in NF-kappaB expression. These data correlated with immunoblotting analyses, which showed significant increases in I-kappaB protein levels and decreased NF-kappaB activity. Additionally, the Bax : Bcl-2 ratio was significantly increased. Our data suggest that both angiogenic and apoptotic genes and proteins are affected by s-thalidomide. Additionally, a dramatic decrease in Bcl-2 expression with s-thalidomide suggests a possible enhancement of cytotoxic effect if combined with other cytotoxic agents.