Live/real time three-dimensional transthoracic echocardiographic visualization of Chiari network

We report the usefulness of live/real time three-dimensional transthoracic echocardiography in the visualization of Chiari network.     

Phonotactic patterns in the speech of children with Down syndrome

Phonotactic patterns of seven 11-15-year-old Kannada speaking children with Down syndrome (DS), mental age matched children with mental retardation (MR) without DS and six 4-5-year-old typically developing (TD) children were investigated. Conversational speech analyses and target analyses of conversational speech were carried out in all three groups of participants. Imitated speech samples from both groups of children with disorders were also analysed with respect to phonotactic patterns. Both conversational and imitated speech analyses revealed that children with DS showed a higher percentage of occurrences of simpler phonotactic patterns than the later acquired complex ones. Target analyses revealed certain similarities in all three groups indicating that while persons with Down syndrome attempted certain complex phonotactic shapes, errors such as consonant deletions, syllable deletions and cluster reductions led to the use of simpler phonotactic patterns. Based on these analyses, the study explores the possible presence of Childhood Apraxia of Speech (CAS) in children with DS and stresses the importance of assessing phonotactic deficits in these children.     

Daboia russelli venom hyaluronidase: purification, characterization and inhibition by β-3-(3-hydroxy-4-oxopyridyl) α-amino-propionic Acid

The present study describes the purification and characterization of a hyaluronidase (DRHyal-II) from Daboia/Vipera russelli venom and its inhibition by β-3-(3-hydroxy-4-oxopyridyl) α-amino-propionic acid, the mimosine. Gel permeation and ion exchange chromatography were employed to isolate DRHyal-II. The molecular mass by MALDITOF mass spectrometry was found to be 28.3 kDa. Single band in reduced SDS-PAGE suggested the monomeric nature. It was optimally active at pH 5.5 and at 37C and require 150 mM NaCl in the reaction mixture. It was specific to hyaluronan substrate and belongs to class-I or the neutral active enzymes. DRHyal-II was non-toxic by itself but, it potentiated the myotoxicity of VRV-PL-VIII myotoxin and hemorrhagic activity of hemorrhagic complex (HC). In in vitro experiments, mimosine inhibited the activity of DRHyal-II and the hyaluronidase activity of whole venom dose dependently. In in vivo experiments, mimosine inhibited the DRHyal-II potentiated myotoxicity of VRV-PL-VIII myotoxin and hemorrhagic activity of HC. The inhibition was due to the formation of DRHyal-II-mimosine inhibitory complex that resulted in significant structural changes at secondary and tertiary levels as evidenced by fluorescence emission and CD spectral studies. Hence, in this study an attempt was made to establish the possible role of hyaluronidase activity in the pathology of Daboia/Vipera russelli venom and the beneficial effects of its inhibition with special emphasis on the management of local toxicity.     

Treatment of midline cleft of the mandible-A 2-stage approach

Midline clefts of the lower lip and mandible are rare congenital anomalies. They may present as complete or incomplete in nature along with associated bifid tongue and ankyloglossia. Some may present with cleft of lower lip, cleft of mandible, fissured tongue, absent hyoid bone, cleft of manubrium sterni, or an extremely rare anomaly known as Tessier cleft no. 30. We present this unique case of midline cleft of the lower lip (incomplete) and mandible (complete) with initial soft-tissue surgery for the lower lip. The hard-tissue surgery for this case is deferred at a later date, and the reasons are discussed.     

Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation

The mechanisms driving bone marrow stem cell mobilization are poorly understood. A recent murine study found that circulating bone marrow-derived osteoprogenitor cells (MOPCs) were recruited to the site of recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone formation. Stromal cell-derived factor-1α (SDF-1α) and its cellular receptor CXCR4 have been shown to mediate the homing of stem cells to injured tissues. We hypothesized that chemokines, such as SDF-1, are also involved with mobilization of bone marrow cells. The CD45(-) fraction is a major source of MOPCs. In this report we determined that the addition of BMP-2 or SDF-1 to collagen implants increased the number of MOPCs in the peripheral blood. BMP-2-induced mobilization was blocked by CXCR4 antibody, confirming the role of SDF-1 in mobilization. We determined for the first time that addition of SDF-1 to implants containing BMP-2 enhances mobilization, homing of MOPCs to the implant, and ectopic bone formation induced by suboptimal BMP-2 doses. These results suggest that SDF-1 increases the number of osteoprogenitor cells that are mobilized from the bone marrow and then home to the implant. Thus, addition of SDF-1 to BMP-2 may improve the efficiency of BMPs in vivo, making their routine use for orthopaedic applications more affordable and available to more patients.     

Clinical and pharmacologic evaluation of two dose levels of intetumumab (CNTO 95) in patients with melanoma or angiosarcoma

Purpose In this Phase 1, multicenter, open-label study, intetumumab (CNTO 95), a fully human anti-αv integrin monoclonal antibody was evaluated for safety, pharmacokinetics, and pharmacodynamic activity in patients with melanoma or angiosarcoma. Patients and methods Patients with histologically-confirmed inoperable melanoma or angiosarcoma refractory to standard treatment were allocated to treatment with 10 mg/kg or 20 mg/kg intetumumab, administered once every 3 weeks for up to four cycles unless unacceptable toxicity or disease progression occurred. Extended dosing was available for patients who responded with stable disease or better. Results Eight patients received 10 mg/kg and 11 received 20 mg/kg intetumumab. Baseline patient characteristics were comparable between treatment groups; 18 patients had metastatic malignant melanoma and one had angiosarcoma. No dose-limiting toxicities were observed. Headache was the most common adverse event across both dose groups. Vomiting, nausea and chills were more common, and uveitic reactions lasted longer, in patients treated with 20 mg/kg compared with 10 mg/kg intetumumab. No patient developed antibodies to intetumumab. Intetumumab drug exposure as assessed by area under the curve and maximum serum concentration appeared to increase approximately dose-proportionally from 10 to 20 mg/kg, while volume of distribution remained constant for both doses. Stable disease was observed in two patients with metastatic malignant melanoma (one in each dose group) for at least 6 weeks. Conclusions In patients with metastatic malignant melanoma and angiosarcoma in this study, intetumumab demonstrated manageable toxicity, was well tolerated, and presented approximately dose-proportional pharmacokinetics for the 10 mg/kg and 20 mg/kg doses.