The effect of vascular endothelial growth factor on the healing of ischaemic skin wounds.

The effect of exogenous vascular endothelium growth factor (VEGF) on wound healing in an ischaemic skin flap model was evaluated in this study. Seventy-two Sprague-Dawley rats were used. Normal incisional wound and H-shaped double flaps were used as the wound models. The study was divided into two parts. In Part I, VEGF protein levels were determined from the incisional and H-shaped ischaemic wounds at 12 and 24 h, postoperatively. In Part II, tensile strength and immunohistochemical stains were examined to determine the level of microvessel density (MVD) at 1 and 2 weeks, postoperatively in simple incisional wounds, ischaemic wounds, and ischaemic wounds following 1 ml (1 microg/ml) exogenous VEGF injections into the subcutaneous tissue. The results showed a significantly higher level of VEGF protein in the ischaemic wounds than the incisional wounds. Tensile strength was statistically higher in the incisional wound group and in the ischaemic flap wounds with VEGF treatment compared to the ischaemic flaps with no treatment at 1 week, postoperatively (p>0.05). MVD data indicated that ischaemic wound repair with VEGF treatment had significantly higher MVD than the normal incisional wounds and ischaemic wounds without treatment. We conclude that exogenous application of VEGF can increase early angiogenesis and tensile strength in the ischaemic wound.     

Dyschromatopsia in subjects occupationally exposed to organic solvents

Chromatic discrimination loss was evaluated with the Lanthony D-15 desaturated Panel among 89 workers professionally exposed to organic solvents and 114 non-exposed workers. Quantitative and qualitative analysis of the results reveal the following: among the non-exposed workers, the prevalence of tritanomalies and the mean colour confusion index increase with age; among the exposed workers, the prevalence of dyschromatopsia and the mean colour confusion index increase with age and with exposure level; for 4% of the moderately exposed workers and 26% of the highly exposed workers, protanomaly, deuteranomaly or scotopic loss were observed with the tritanomaly. Chromatic discrimination impairment may be an important indicator of neuro-ophthalmologic changes associated with professional exposure to organic solvents.     

Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Genetic testing for inherited eye conditions in over 6,000 individuals through the eyeGENE network

Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE®, the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish a phenotype:genotype database, biorepository, and patient registry. Data and samples are available for research use, and participants are provided results of clinical genetic testing. eyeGENE utilized a unique, distributed clinical trial design to enroll 6,403 participants from 5,385 families diagnosed with over 30 different inherited eye conditions. The most common diagnoses given for participants were retinitis pigmentosa (RP), Stargardt disease, and choroideremia. Pathogenic variants were most frequently reported in ABCA4 (37%), USH2A (7%), RPGR (6%), CHM (5%), and PRPH2 (3%). Among the 5,552 participants with genetic testing, at least one pathogenic or likely pathogenic variant was observed in 3,448 participants (62.1%), and variants of uncertain significance in 1,712 participants (30.8%). Ten genes represent 68% of all pathogenic and likely pathogenic variants in eyeGENE. Cross‐referencing current gene therapy clinical trials, over a thousand participants may be eligible, based on pathogenic variants in genes targeted by those therapies. This article is the first summary of genetic testing from thousands of participants tested through eyeGENE, including reports from 5,552 individuals. eyeGENE provides a launching point for inherited eye research, connects researchers with potential future study participants, and provides a valuable resource to the vision community.