Posterior uveal melanomas have recurrent alterations of chromosomes 1, 3, 6 and 8. In particular, changes of chromosomes 3 and 8 occur in association, appear to characterize those tumours with a ciliary body component, and have been shown to be of prognostic significance. The relevance of other chromosome alterations is less certain. We have performed cytogenetic analysis on 42 previously untreated primary posterior uveal melanomas. Of interest was the observation that as tumour size increased the involvement of specific chromosome changes, and the amount of chromosome abnormalities likewise increased. Loss, or partial deletions, of the short arm of chromosome 1 were found to associate with larger ciliary body melanomas; typically, loss of the short arm resulted from unbalanced translocations, the partners of which varied. Trisomy of chromosome 21 occurred more often in ciliary body melanomas, whilst rearrangements of chromosomes 6 and 11 were primarily related to choroidal melanomas. Our results imply that alterations of chromosome 1 are important in the progression of some uveal melanomas, and that other chromosome abnormalities, besides those of chromosomes 3 and 8, are associated with ocular tumours of particular locations. © 2000 Cancer Research Campaign
Summary Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by a polyglutamine expansion in the androgen receptor (AR) and is associated with misfolding and aggregation of the mutant AR. We investigated the role of an interdomain interaction between the amino (N)-terminal FxxLF motif and carboxyl (C)-terminal AF-2 domain in a mouse model of SBMA. Male transgenic mice expressing polyQ-expanded AR with a mutation in the FxxLF motif (F23A) to prevent the N/C interaction displayed substantially improved motor function, compared to N/C-intact AR-expressing mice, and showed reduced pathological features of SBMA. Serine 16 phosphorylation was substantially enhanced by the F23A mutation; moreover, the protective effect of AR F23A was dependent on this phosphorylation. These results reveal an important role for the N/C interaction on disease onset in mice, and suggest that targeting AR conformation could be a therapeutic strategy for patients with SBMA.
A single intramuscular application of the live but not UV-inactivated recombinant rabies virus (RABV) variant TriGAS in mice induces the robust and sustained production of RABV-neutralizing antibodies that correlate with long-term protection against challenge with an otherwise lethal dose of the wild-type RABV. To obtain insight into the mechanism by which live TriGAS induces long-lasting protective immunity, quantitative PCR (qPCR) analysis of muscle tissue, draining lymph nodes, spleen, spinal cord, and brain at different times after TriGAS inoculation revealed the presence of significant copy numbers of RABV-specific RNA in muscle, lymph node, and to a lesser extent, spleen for several days postinfection. Notably, no significant amounts of RABV RNA were detected in brain or spinal cord at any time after TriGAS inoculation. Differential qPCR analysis revealed that the RABV-specific RNA detected in muscle is predominantly genomic RNA, whereas RABV RNA detected in draining lymph nodes is predominantly mRNA. Comparison of genomic RNA and mRNA obtained from isolated lymph node cells showed the highest mRNA-to-genomic-RNA ratios in B cells and dendritic cells (DCs), suggesting that these cells represent the major cell population that is infected in the lymph node. Since RABV RNA declined to undetectable levels by 14 days postinoculation of TriGAS, we speculate that a transient infection of DCs with TriGAS may be highly immunostimulatory through mechanisms that enhance antigen presentation. Our results support the superior efficacy and safety of TriGAS and advocate for its utility as a vaccine. Rabies is a zoonotic disease that continues to be an important public health problem causing an estimated 55,000 human deaths each year globally, the majority of which occur in Africa and Asia (1). In Asia, parts of America, and large parts of Africa, canines remain the principal host of rabies virus (RABV), and more than 95% of all human rabies cases are caused by exposure to infected dogs (2, 3). The most effective means to protect humans and livestock against rabies is by prophylactic immunization with an RABV vaccine. Although inactivated tissue culture RABV vaccines are safe, they induce protective immunity only when administered in multiple doses and generally require repeat booster doses to provide long-lasting protection. Repeated prophylactic immunization is cost-prohibitive and operationally unrealistic for both people and animals in developing countries. A single-dose RABV vaccine capable of inducing robust, enduring immunity would be highly advantageous in controlling rabies in dogs, livestock, and humans worldwide.A hallmark of wild-type RABV is its neuroinvasiveness-a unique ability to invade the central nervous system (CNS) from peripheral sites of inoculation (4, 5). Important aspects of this property include the capacity to preserve the integrity of the neuronal network and the ability to evade host immunity (6, 7). One of the important mechanisms that contribute to both of these features of rabies pathogenes...
BackgroundThe transradial approach (TRA) reduces mortality, morbidity, access site complications, hospital cost, and length of stay while maximizing patient satisfaction. We aimed to assess the technical success and safety of TRA for elderly patients (aged ≥75 years).MethodsA retrospective chart review and comparative analysis was performed for elderly patients undergoing a diagnostic cerebral angiogram performed via TRA versus transfemoral approach (TFA). Also, a second comparative analysis was performed among the TRA cohort between elderly patients and their younger counterparts.ResultsComparative analysis in the elderly (TRA vs TFA) showed no significant differences for contrast dose per vessel (43.7 vs 34.6 mL, P=0.106), fluoroscopy time per vessel (5.7 vs 5.2 min, P=0.849), procedure duration (59.8 vs 65.2 min, P=0.057), conversion rate (5.8% vs 2.9%, P=0.650), and access site complications (2.3% vs 2.9%, P=1.00). Radiation exposure per vessel (18.9 vs 51.9 Gy cm2, P=0.001) was significantly lower in the elderly TRA group.The second comparison (TRA in elderly vs TRA in the young) showed no significant differences for contrast dose per vessel (43.7 vs 37.8 mL, P=0.185), radiation exposure per vessel (18.9 vs 16.5 Gy cm2, P=0.507), procedure duration (59.8 vs 58.3 min, P=0.788), access site complication (2.3% vs 1.7%, P=0.55), and conversation rate (5.8% vs 1.8%, P=0.092). A trend for prolonged fluoroscopy time per vessel (5.7 vs 4.7 min, P=0.050) was observed in the elderly TRA group.ConclusionsTRA is a technically feasible and safe option for diagnostic neurointerventional procedures in the elderly. Our small elderly cohort was not powered enough to show a significant difference in terms of access site complications between TRA and TFA.
BACKGROUND The radial approach has been gaining more widespread use by neurointerventionalists fueled by data from the cardiology literature showing better safety and overall reduced morbidity. OBJECTIVE To present our institution's experience with the radial approach for neuroendovascular interventions in 614 consecutive patients who underwent a cumulative of 760 procedures. METHODS A retrospective analysis was performed and identified neuroendovascular procedures performed via the upper extremity vasculature access site. RESULTS Amongst 760 procedures, 34.2% (260) were therapeutic, and 65.7% (500) were nontherapeutic angiograms. Access sites were 71.5% (544) via a conventional radial artery, 27.8% (211) via a distal radial artery, 0.5% (4) via an ulnar artery, and 0.1% (1) via the brachial artery. Most of the procedures (96.9%) were performed via the right-sided (737), 2.9% (22) via the left-sided, and 0.1% (1) via a bilateral approach. Major access site complications occurred at a rate of 0.9% (7). The rate of transfemoral conversion was 4.7% (36). There was a statistically higher incidence of transfemoral conversion when repeat procedures were performed using the same access site. Also, there was no significant difference between nontherapeutic procedures performed using the right and left radial access, and conventional versus distal radial access. Procedural metrics improved after completion of 14 procedures, indicating a learning curve that should be surpassed by operators to reach optimal outcomes. CONCLUSION Radial artery catheterization is a safe and effective means of carrying out a wide range of neuroendovascular procedures associated with excellent clinical outcomes and an overall low rate of periprocedural complications.
A microcomputer-based teleradiology system was tested over a six-month period by linking a medical center with four distant clinics. Data from more than 4,000 diagnostic x-ray examinations were digitized and transmitted from the clinics to the center, where they were displayed on video terminals and interpreted by 30 military and civilian radiologists. The original radiographs were interpreted independently and the video and film reports compared to determine the feasibility of the teleradiology system. Evaluation of the clinical effectiveness of the system indicated that the quality of the video images resulted in diagnostic findings and impressions that were somewhat less accurate than those reported from comparable film images.
BACKGROUND Distal transradial catheterization in the anatomic snuffbox is an alternate route of access that has started to gain consideration for neuroendovascular procedures. OBJECTIVE To assess the feasibility and outcomes and present our institution's experience in performing neuroendovascular procedures via distal transradial access (dTRA). METHODS We conducted a retrospective analysis and identified 120 patients who underwent consecutive neuroendovascular procedures via dTRA in the anatomic snuffbox. Data collection was performed on indication for procedure, sheath size, number of vessels selectively catheterized, fluoroscopy time, procedure duration, radiation exposure, conversion to femoral approach, access site complication, and procedure success. RESULTS Of 120 patients with an average age of 54.7 yr ± 14.7, 73 (60.8%) underwent diagnostic angiograms, 38 (31.7%) underwent follow-up angiograms, and 9 (7.5%) underwent therapeutic procedures. The overall mean number of vessels catheterized was 2.5 ± 0.1 per procedure, the mean procedure time was 68.3 min ± 43.4, the mean fluoroscopy time was 10.8 min ± 7.6, the mean contrast dose was 70.6 mL ± 39.1, and the mean radiation exposure was 27 672.2 mGycm2 ± 42 728.4. Successfully completed therapeutic procedures included aneurysm 1 (0.8%), arteriovenous malformation (AVM)/arteriovenous fistula/carotid cavernous fistula 7 (5.8%), and 1 (0.8%) other treatment. Three patients (2.5%) required adjunct transfemoral endovenous access for AVM embolization. Two minor complications (1.67%) were a local wrist hematoma and a radial artery vasospasm without any sequelae. CONCLUSION Distal radial artery catheterization in the anatomic snuffbox is a safe and effective access site to perform neuroendovascular procedures. Complications and conversion rate are low making it a safe alternative.
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