Aortic dissection: percutaneous management of ischemic complications with endovascular stents and balloon fenestration

PURPOSE: The purpose of this study was to evaluate endovascular stenting (EVS) and balloon fenestration (BF) of intimal flaps for the management of lower extremity, renal, and visceral ischemia in acute or chronic aortic dissection. METHODS: Twenty-two patients (16 male, 6 female) with a median age of 53 years (range 35 to 77 years) underwent percutaneous treatment for peripheral ischemic complications of 12 type A (five acute, seven chronic) and 10 type B (nine acute, one chronic) aortic dissections. RESULTS: Ten patients had leg ischemia, 13 had renal ischemia, and 6 had visceral ischemia. Sixteen patients were treated with EVS including 11 with renal, 6 with lower extremity, 2 with superior mesenteric artery, and 2 with aortic stents. Three patients had BF of the intimal flap, and three had BF in combination with EVS. Revascularization with clinical success was achieved in all 22 patients. Two patients died 3 days and 13.4 months after the procedure was performed, respectively. Of the remaining 20 patients, 1 is lost to follow-up, and 19 have persistent relief of clinical symptoms. Mean follow-up time is 13.7 months (range 1.1 to 46.5 months). One case was complicated by guidewire-induced perinephric hematoma. CONCLUSION: EVS and BF provide a safe and effective percutaneous method for managing peripheral ischemic complications of aortic dissection.     

Capacitative Ca2+ entry and the regulation of smooth muscle tone

In many non-excitable cells, activation of phospholipase C-linked receptors results in a biphasic increase in the cytosolic Ca2+ concentration; an initial transient increase, owing to the release of Ca2+ from the endoplasmic/sarcoplasmic reticulum (ER/SR), is followed by a much smaller but sustained elevation, which often involves capacitative Ca2+ entry, where depletion of Ca2+ within the ER signals the opening of store-operated Ca2+ channels in the plasma membrane. However, in excitable cells such as smooth muscle, the role of capacitative Ca2+ entry is less clear and the main Ca2+ entry mechanisms responsible for sustained cellular activation have been considered to be either voltage-operated or receptor-operated Ca2+ channels. Although store-regulated Ca2+ entry was known to occur following agonist activation of smooth muscle, it was believed to be important only for the re-filling of the depleted SR and not as a source of activator Ca2+ for the contractile mechanisms. Here, Alan Gibson, Ian McFadzean, Pat Wallace and Christopher Wayman review recent evidence that capacitative Ca2+ entry might indeed be important for the regulation of smooth muscle tone, and that it might provide an important for pharmacological intervention.     

TNK-tissue plasminogen activator compared with front-loaded alteplase in acute myocardial infarction: results of the TIMI 10B trial. Thrombolysis in Myocardial Infarction (TIMI) 10B Investigators

BACKGROUND: Bolus thrombolytic therapy is a simplified means of administering thrombolysis that facilitates rapid time to treatment. TNK-tissue plasminogen activator (TNK-tPA) is a highly fibrin-specific single-bolus thrombolytic agent. METHODS AND RESULTS: In TIMI 10B, 886 patients with acute ST-elevation myocardial infarction presenting within 12 hours were randomized to receive either a single bolus of 30 or 50 mg TNK-tPA or front-loaded tPA and underwent immediate coronary angiography. The 50-mg dose was discontinued early because of increased intracranial hemorrhage and was replaced by a 40-mg dose, and heparin doses were decreased. TNK-tPA 40 mg and tPA produced similar rates of TIMI grade 3 flow at 90 minutes (62.8% versus 62.7%, respectively, P=NS); the rate for the 30-mg dose was significantly lower (54.3%, P=0.035) and was 65. 8% for the 50-mg dose (P=NS). A prespecified analysis of weight-based TNK-tPA dosing using median TIMI frame count demonstrated a dose response (P=0.001). Similar dose responses were observed for serious bleeding and intracranial hemorrhage, but significantly lower rates were observed for both TNK-tPA and tPA after the heparin doses were lowered and titration of the heparin was started at 6 hours. CONCLUSIONS: TNK-tPA, given as a single 40-mg bolus, achieved rates of TIMI grade 3 flow similar to those of the 90-minute bolus and infusion of tPA. Weight-adjusting TNK-tPA appears to be important in achieving optimal reperfusion; reduced heparin dosing appears to improve safety for both agents. Together with the safety results from the parallel Assessment of the Safety of a New Thrombolytic: TNK-tPA (ASSENT I) trial, an appropriate dose of this single-bolus thrombolytic agent has been identified for phase III testing.     

Immunolocalization of interstitial collagenase (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in radicular cysts

To investigate the mechanisms involved in expansion of radicular cysts, monoclonal antibodies against interstitial collagenase (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were used to localize the sites of MMP-1 and TIMP-1 expression in 30 radicular cysts. Positive MMP-1 staining was detected in the lining epithelium and subepithelial fibroblasts, macrophages, endothelial cells and osteoblasts/osteocytes in all specimens. Positive TIMP-1 staining was identified in osteoblasts/osteocytes and endothelial cells of all specimens, and in the lining epithelium and subepithelial fibrous connective tissue wall of five radicular cysts with an intense inflammatory cell infiltrate. The number and distribution of positive cells for MMP-1 or TIMP-1 varied widely among individual specimens, but strong immunostaining was constantly detected at sites with prominent subepithelial inflammation. Results here support the hypothesis that MMP-1 may play an important role in the expansion of radicular cysts. The absence of TIMP-1 expression in lining epithelium and subepithelial fibroblasts and macrophages in most cases studied indicated that an imbalance between MMP-1 and TIMP-1 production may lead to radicular cyst expansion.     

p53 antibodies in patients with various types of cancer: assay, identification, and characterization

Alteration of the p53 gene is the most frequent genetic alteration in human cancer and leads to the accumulation of mutant p53 in the nucleus of tumor cells. In addition, it has been shown that patients with various types of neoplasia have p53 antibodies in their sera which could be used as an indirect diagnostic procedure for p53 alteration. Using a new ELISA, we have analyzed the sera from more than 1000 patients with various types of cancer and from healthy blood donors. We demonstrate that p53 antibodies are detected mainly in cancer patients and are strictly proportional to the occurrence of p53 mutations. Using various immunological approaches, these antibodies were unambiguously demonstrated to be directed toward the human p53 protein. Isotyping analysis of these antibodies strongly suggested that they correspond to a humoral response to the p53 protein which accumulates in the tumor cell. This finding suggests that serological analysis, combined with histochemistry, is suitable for assessing the integrity of the p53 gene in cancer patients.     

Comparison of an extraconal block with a retrobulbar-facial block combination for ocular surgery. A safe alternative technique to the combination of retrobulbar block and facial nerve block

Four hundred and eight consecutive patients scheduled for cataract surgery under local anaesthesia were randomly allocated to one of two types of regional anaesthesia. One group was given the standard retrobulbar block combined with a facial nerve block of the O'Brien type, and the second group was given a modified peribulbar block. Results indicate that it is possible to achieve a high degree of reliability, within a relatively short time, from the modified peribulbar block without the major complications associated with retrobulbar block.