SummaryV(D)J recombination of immunoglobulin loci is dependent on the immune cell-specific Rag1 and Rag2 proteins as well as a number of ubiquitously expressed cellular DNA repair proteins that catalyze non-homologous end-joining of DNA double-strand breaks. The evolutionarily conserved Rad50/Mre11/Nibrin protein complex plays a role in DNA double-strand break-repair, suggesting that these proteins, too, may participate in V(D)J recombination. Recent findings demonstrating that Rad50 function is defective in cells from patients afflicted with Fanconi anemia provide a possible mechanistic explanation for previous findings that lymphoblasts derived from these patients exhibit subtle defects in V(D)J recombination of extrachromosomal plasmid molecules. Herein we describe a series of findings that provide convincing evidence for a role of the Rad50 protein complex in V (D)J recombination. We found that the fidelity of V(D)J signal joint recombination in fibroblasts from patients afflicted with Fanconi anemia was reduced by nearly 10-fold, compared to that observed in fibroblasts from normal donors. Second, we observed that antibody-mediated inhibition of the Rad50, Mre11, or Nibrin proteins significantly reduced the fidelity of signal joint recombination in wild-type cells. The latter finding was somewhat unexpected because signal joint rejoining in cells from patients with Nijmegen breakage syndrome, which results from mutations in the Nibrin gene, occurs with normal fidelity. However, introduction of anti-Nibrin antibodies into these cells dramatically reduced the fidelity of signal joint recombination. These data reveal a heretofore unreported role for the Rad50 complex in V(D)J recombination, and demonstrate that the protein product of the disease-causing allele responsible for Nijmegen breakage syndrome encodes a protein with residual DNA double-strand break repair activity.
Case Presentation: We report the case of a 35-year-old female, recently diagnosed with neurofibromatosis type 1 (NF-1) during early prenatal visits who acutely presented with rapidly progressing right upper extremity swelling and pain and numbness of the fingers but intact sensorimotor exam. While upon presentation the patient was hemodynamically stable, shortly after discovery of a large psuedoaneurysm by bedside Doppler, the patient developed soft systolic pressures. With concern for rupture of the pseudoaneurysm, the patient was immediately taken into the vascular surgery operating room. Technique: A large right upper extremity subcutaneous hematoma was discovered. The soft tissues were friable, and the brachial artery and its accompanying veins were brittle. Obtaining hemostasis was challenging but achieved with gentle handling of the tissues, further sutures, hemoclips, topical thrombin (Gelfoam), Arista, and Surgicels. The ruptured right brachial artery pseudoaneurysm was repaired using a composite polytetrafluoroethylene graft and great saphenous vein graft from the right axillary artery to the right brachial artery. In addition, the patient had interposition graft vein repair from the right brachial vein to the right axillary vein. Her postoperative course was significant for brachial fascial compartment syndrome, but, due to the friability of the tissue, was not reoperated. On the seventh postoperative day, computed tomography angiography confirmed that the patient's right brachial artery reconstruction was patent. Discussion: Vascular complications in the setting of neurofibromatosis are rare, but often serious and may be fatal. Few patients with NF-1 and a ruptured brachial artery aneurysm have been reported, with one successful case of reconstruction of the ruptured brachial artery. One case of brachial artery rupture in a peripartum patient with NF-1 has been reported; following an unsuccessful reconstruction attempt, amputation was necessary. Surgery in NF-1 patients with peripheral extremity pseudoaneurysm rupture is challenging and risky due to tissue friability and potential for significant intraoperative bleeding.
Patient demographics, presenting complaints, operative details, and complications were analyzed. Postoperative patency was assessed by comparison of ankle-brachial index values and qualitative patient improvement. Data was analyzed by way of paired Student t-test and c 2 values with significance defined as a P value of <.05. Results: A total of 39 limbs were intervened upon in 32 patients. In 19 limbs (49% of patient cohort), the procedure was performed for critical limb ischemia (n ¼ 8, rest pain; n ¼ 11, tissue loss/gangrene). Twenty-five limbs (64%) received an external iliac artery stent with procedure. The median external iliac artery stent diameter was 10 mm (range, 8-16 mm). The preintervention ankle-brachial index was 0.45 6 0.24 (n ¼ 32 limbs) and significantly improved to 0.74 6 0.27 (n ¼ 28 limbs; P < .001). In addition, preintervention toe pressure of 34 6 28 (n ¼ 27 limbs) improved to 58 6 26 (n ¼ 22 limbs; P < .001). Average follow-up postintervention was 13 6 14.6 months. One limb (3%) required an additional outflow bypass. At last follow-up, no patient needed subsequent primary assisted patency or additional infrainguinal revascularization. Conclusions: Hybrid-based external iliac and femoral endarterectomy provides a robust, less invasive approach to severe external iliac stenosis or occlusion compared to aortofemoral bypass. Dramatic inflow improvement was observed in our series, and the need for additional outflow revascularization was virtually eliminated. The procedure was deemed technically feasible and safe, with a low number of adverse sequela and excellent primary patency achieved more than 1 year postintervention.
there is limited data regarding the outcomes of patients undergoing cardiac revascularization to achieve transplant candidacy, particularly in patients receiving percutaneous coronary intervention (PCI). We investigated the outcomes of potential transplant candidates who underwent PCI and assessed their post-intervention outcomes.
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