Circulating Anti-neutrophil Cytoplasmic Autoantibodies in Subglottic Stenosis: a Useful Aid in Diagnosing Vasculitis in This Condition?

Five patients with subglottic stenosis, occurring either asa presenting symptom or as a manifestation in the course ofa systemic disease, are described. Indirect immunofluorescencerevealed the presence of circulating autoantibodies againstboth cytoplasmic and perinuclear constituents of neutrophilsin all five. Antibodies directed against a 29 kDa antigen ofthe azurophilic granules (two patients), against myeloperoxidase(one patient), and against both the 29 kDa antigen and myeloperoxidase(one patient) were found by enzyme-linked immunosorbent assay.These autoantibodies have previously been found in patientswith Wegener's granulomatosis, microscopic polyarteritis, (idiopathic)glomerulonephritis and Churg-Strauss syndrome. However, onlyone of these five patients fulfilled the criteria for theseconditions. Since these autoantibodies are seldom observed inother conditions, and other diseases had been excluded by carefulevaluation, we suggest that their presence places subglotticstenosis within the spectrum of necrotizing (granulomatous)vasculitis. Whether immunosuppressive therapy is always warrantedin patients with subglottic stenosis and circulating anti-neutrophilcytoplasmic antibodies is a matter of debate.     

Integration of adeno-associated virus vectors in CD34+ human hematopoietic progenitor cells after transduction

Gene transfer vectors based on adeno-associated virus (AAV) appear promising because of their high transduction frequencies regardless of cell cycle status and ability to integrate into chromosomal DNA. We tested AAV-mediated gene transfer into a panel of human bone marrow or umbilical cord-derived CD34+ hematopoietic progenitor cells, using vectors encoding several transgenes under the control of viral and cellular promoters. Gene transfer was evaluated by (1) chromosomal integration of vector sequences and (2) analysis of transgene expression. Southern hybridization and fluorescence in situ hybridization analysis of transduced CD34 genomic DNA showed the presence of integrated vector sequences in chromosomal DNA in a portion of transduced cells and showed that integrated vector sequences were replicated along with cellular DNA during mitosis. Transgene expression in transduced CD34 cells in suspension cultures and in myeloid colonies differentiating in vitro from transduced CD34 cells approximated that predicted by the multiplicity of transduction. This was true in CD34 cells from different donors, regardless of the transgene or selective pressure. Comparisons of CD34 cell transduction either before or after cytokine stimulation showed similar gene transfer frequencies. Our findings suggest that AAV transduction of CD34+ hematopoietic progenitor cells is efficient, can lead to stable integration in a population of transduced cells, and may therefore provide the basis for safe and efficient ex vivo gene therapy of the hematopoietic system.     

Noninfiltrating angiolipoma of the mediastinum

A case of mediastinal angiolipoma in a 63-year-old man is described. A computed tomographic scan of the thorax demonstrated a large encapsulated mass with fatty and soft-tissue components near the esophagus. This appearance was considered suggestive of a liposarcoma. However, at surgery a benign noninfiltrating angiolipoma was found and removed. To the authors' knowledge, angiolipomas have not previously been reported to occur within the mediastinum.     

Pseudoaneurysms complicating pancreatitis: detection by CT

Complications of pancreatitis such as pseudocyst formation and abscess are well known to radiologists. Secondary formation of pseudoaneurysms has not been emphasized in the radiologic literature. The great morbidity and mortality associated with pseudoaneurysms emphasize the importance of early detection. Three patients are described whose angiographically proved pseudoaneurysms were demonstrated on contrast material-enhanced abdominal CT scans obtained for evaluation of pancreatitis. A homogeneously enhancing structure within or adjacent to a pancreatic pseudocyst or contiguous with a vascular structure should be considered highly suspicious for an associated pseudoaneurysm.     

Regulation of endoplasmic reticulum Ca2+ dynamics by proapoptotic BCL-2 family members

Uncontrolled cytosolic Ca(2+) overload is a common cause of cell death in several pathological conditions. Recent evidences reveal a more regulated role for intracellular Ca(2+) stores in controlling cell death. Proteins of the BCL-2 family include anti- and proapoptotic members that control the mitochondrial amplification loop of apoptosis. The antiapoptotic protein BCL-2 prevents this mitochondrial loop, while the "multidomain" proapoptotic proteins BAX and BAK are crucial to initiate it. BCL-2, BAX and BAK localize also to the endoplasmic reticulum (ER), the main intracellular Ca(2+) store. Overexpression of BCL-2 reduces resting ER Ca(2+) and death in response to apoptotic stimuli that mobilize Ca(2+). Our recent data indicate that multidomain proapoptotics also influence Ca(2+) metabolism. Cells deficient for Bax, Bak (DKO) display lowered steady state ER Ca(2+) concentrations ([Ca(2+)](er)) and secondarily decreased mitochondrial Ca(2+) uptake. Genetic and pharmacologic correction of [Ca(2+)](er) indicates that it controls death in response to Ca(2+)-dependent, mitochondria utilizing signals such as oxidative stress and lipid mediators; and that it participates in the regulation of the apoptotic response to most intrinsic stimuli, such as staurosporine. Thus, BAX and BAK control apoptosis not only at the mitochondria, but also at the ER, an obligate checkpoint for Ca(2+)-dependent apoptotic stimuli.     

A prospective,randomised trial of preoperative rectal diclofenac: Are we closing the gate after the horse has gone?

Background Diclofenac sodium is a non-steroidal anti-inflammatory agent commonly used to provide analgesia postsurgery. It is common clinical practice to administer a diclofenac suppository at induction to contribute to pre-emptive analgesia (PEA). Diclofenac takes up to 30 minutes to attain maximal plasma level after rectal administration. Aim To compare post-operative analgesia in patients who received diclofenac 30–45 minutes preoperatively, or at induction of anaesthesia. Methods A prospective, randomised, double-blind controlled trial in 157 patients undergoing varicose vein surgery. Group A (control) received a rectal placebo 30–45 minutes preoperatively, group B received diclofenac 100mg 30–45 minutes preoperatively and group C received placebo 30–45 minutes preoperatively and diclofenac 100mg at induction. Outcome measures were Visual Analogue Scores (VAS) and requirement for rescue analgesia. Results Patients in group A had significantly poorer analgesia than patients in groups B and C. There were no significant differences in VAS values and requirements for rescue analgesia between groups B and C 3–4 hours and 18–22 hours postoperatively. Conclusion For patients undergoing varicose vein surgery preoperative administration of rectal diclofenac significantly improves post-operative analgesia and this effect is independent of whether it is given at induction or 30– 45 minutes preoperatively.