Intracranial circulation: pulse-sequence considerations in three- dimensional (volume) MR angiography

The technique and feasibility of magnetic resonance (MR) angiography of intracranial vessels were studied in 35 healthy volunteers. Variations in image orientation, repetition time (TR), and flip angle were evaluated to determine their effects on flow-related enhancement. Gradient modifications--including echo time (TE), motion compensation, bandwidth, and field of view--were also studied in an effort to reduce motion-induced phase shifts. Results indicated that a FISP (fast imaging with steady precession) sequence with a TR of 50 msec, TE of 15 msec, velocity compensation in the read and section-select directions, acceleration compensation in the read direction, anisotropic volume, and a 1.25-mm partition thickness produced three-dimensional angiographic MR images that were accurate and reproducible in the depiction of the major intracranial vessels. Difficulties with field of view, persistent signal void secondary to higher-order motion, and spatial resolution remain major problems requiring additional study.     

Prognosis in chronic lymphocytic leukemia: a retrospective multicentric study from the GIMEMA group

Clinical and biological data were evaluated using Desu univariate analyses or Cox multivariate analyses in a series of 1,777 chronic lymphocytic leukemia (CLL) patients from an Italian Cooperative Group. In univariate analyses, age and sex of patients, presence of bone marrow (BM; greater than or equal to 50%), and peripheral blood (PB; greater than or equal to 60,000/microL) lymphocytosis, anemia (hemoglobin [Hb] less than 11 g/dL), thrombocytopenia (less than 100,000/microL), direct Coombs' test positivity, hepatomegaly, splenomegaly, and extent of lymph node involvement were shown to be of significant prognostic value. Multivariate analyses, through a stepwise procedure, showed that the most important prognostic variables are Hb, hepatomegaly, lymph node involvement, PB lymphocytosis, and age and sex of patients. Further covariates would produce an improvement having a nonsignificant P value. Based on the results of multivariate analyses, a four-step staging using the significant variables of the Cox model is proposed.     

AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

Elective laparoscopic-assisted colectomy for sigmoid diverticulitis.

OBJECTIVES: The aim of this study was to evaluate the safety and effectiveness of laparoscopic-assisted sigmoid colectomy for diverticulitis and to assess its postoperative advantages. METHODS: From 1999 to 2001, 5 patients were selectively operated on with a laparoscopic-assisted procedure for uncomplicated sigmoid diverticulitis. In the preceding period (September 1997 through December 1998), 4 patients underwent open procedures for the same pathology. The surgical indication with the same criteria was restrictive: at least 2 acute episodes had occurred that were treated with hospital admission and that were separated by an adequate period (2 months) of medical therapy. RESULTS: No conversions of laparoscopy to an open procedure were necessary. Age, sex, weight, morbidity, and mortality were similar between the 2 groups. Operative time was 180 minutes for laparoscopy and 120 minutes for laparotomy. Postoperative resumption of peristalsis was 24 hours versus 4 days, resumption of alimentation was on the second postoperative day versus the fifth postoperative day, and hospital stay was 7 days versus 12 days for laparoscopy and laparotomy, respectively. CONCLUSION: This study shows the feasibility and the advantages of elective laparoscopic-assisted colonic resection for uncomplicated sigmoid diverticulitis. The advantages of the laparoscopic approach are the lower need for analgesics and the more precocious ambulation, canalization, resumption of alimentation, and the shorter hospital stay.     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

Human antibody against C domain of tenascin-C visualizes murine atherosclerotic plaques ex vivo.

Targeting proteins that are overexpressed in atherosclerotic plaques may open novel diagnostic applications. The C domain of tenascin-C is absent from normal adult tissues but can be inserted during tumor progression or tissue repair into the molecule by alternative splicing. We tested the ability of the human antibody G11, specific to this antigen, to reveal murine atherosclerotic plaques ex vivo. The antibody directed against the extra domain B of fibronectin (L19) was used as a reference. METHODS: We intravenously injected (125)I-labeled G11 or L19 antibodies into apolipoprotein E-deficient (ApoE(-/-)) mice and harvested the aortae 4 or 24 h later. En face analyses of distal aortae and longitudinal sections of the aortic arch were performed to compare antibody uptake using autoradiography with plaque staining using oil red O. Plaque macrophages were detected by immunohistochemistry (anti-CD68 staining). Biodistribution of injected antibodies was investigated in aortae and blood at 4 and 24 h. RESULTS: En face analyses revealed a significant correlation between radiolabeled G11 and fat-stained areas, increasing from 4 to 24 h, with a correlation coefficient of 0.92 (P < 0.0001) and an average signal-to-noise ratio of 104:1 at 24 h. Plaque imaging using L19 showed similar results (r = 0.86; P < 0.0001; signal-to-noise ratio, 72:1 at 24 h). Uptake of radiolabeled antibodies in histologic sections colocalized with fat staining and activated macrophages in aortic plaques. Biodistribution analyses confirmed specific accumulation in aortic plaques as well as rapid blood pool clearance of the antibodies 24 h after injection. Immunofluorescence analyses revealed increased expression of tenascin and fibronectin isoforms in macrophage-rich plaques. CONCLUSION: The antibody G11, specific to the C domain of tenascin-C, visualizes murine atherosclerotic plaques ex vivo. In conjunction with the increased expression of the C domain of tenascin-C in macrophage-rich plaques, the colocalization of G11 uptake with activated macrophages, and the favorable target-to-blood ratio at 24 h, this antibody may be useful for molecular imaging of advanced atherosclerotic plaques in the intact organism.     

Limited role of aortic size in the genesis of acute type A aortic dissection

Objective: Increased dimension of the aortic root and proximal aorta is considered a significant risk factor for catastrophic events that involve the ascending aorta. The objective of this study was to determine the possible correlation between pre-dissection aortic diameter and the occurrence of Stanford type A aortic dissection. Methods: Samples of dissected ascending aortas were obtained from 220 patients at the time of their operation. Two groups were identified: patients with connective tissue disorders (Group 1, n = 94) and those without (Group 2, n = 126). Measurements of the true (intimal) lumen were conducted and extrapolated as reliable approximation of pre-dissection aortic diameter. The possible association of intimal diameter with anthropometric and demographic data was analyzed. Results: Median aortic diameter was, respectively, 41.8 and 41.3 mm for patients with and without connective tissue disorders (41.4 mm for the entire cohort). Data analysis indicated that 57% of patients had aortic diameter above 40 mm, while patients with frank aneurysm accounted only for 10%; this proportion was higher in Group 1 compared to Group 2 (17.2% vs 4.7%). Poor or no correlation was demonstrated between aortic size and any of the anthropometric or demographic variables essayed. Significant subgroup differences were found among patients with a history of cigarette smoking, hypertension, diabetes, chronic renal insufficiency, and bicuspid aortic valve. Conclusion: Although aortic diameter remains a strong indication for preventive surgery in patients with inherited connective tissue disorders, acute aortic dissection occurs rarely in the setting of true ascending aortic aneurysms, and despite normal or near-normal aortic size in more than one-third of subjects. Dissection superimposing on small aortic diameters can be regarded as an expression of substantial functional tissue susceptibility to aortic catastrophic events.     

Analysis of ischemia-reperfusion injury in a microcirculatory model of pressure ulcers

The aim of this study was to establish a pressure ulcer model that visualizes the microcirculation, and to examine the participation of ischemia-reperfusion injury in the pathophysiology of pressure ulcers. An original system composed of a new skin fold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia-reperfusion injury, animals were divided into two groups: the compression-release group (n = 8), in which the animals received four cycles of compression-release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group (n = 8) in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day 1 (35 hours) after the first evaluation. The cyclic compression-release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia-reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. This finding supports the significant contribution of ischemia-reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.     

Analysis of alterations of oncogenes and tumor suppressor genes in chronic lymphocytic leukemia.

B cell chronic lymphocytic leukemia (B-CLL) represents the most frequent adult leukemia in the Western world. The molecular pathogenesis of B-CLL is largely unknown. Although initial reports on small panels of cases had suggested a role for Bcl-1 and Bcl-2 oncogene activation in B-CLL, later investigations failed to confirm these data. Among tumor suppressor genes, p53 mutations have been reported in a fraction of cases. In this study, we have attempted a conclusive definition of the involvement of dominantly acting oncogenes (Bcl-1 and Bcl-2) and tumor suppressor loci (p53, 6q-) in 100 cases of B-CLL selected for their CD5 positivity and Rai's stage (0 to IV). Rearrangements of Bcl-1 and Bcl-2 and deletions of 6q and 17p were analyzed by Southern blot using multiple probes. Mutational analysis (single strand conformation polymorphism and polymerase chain reaction direct sequencing) was used to assay p53 inactivation. No alterations of Bcl-1 or Bcl-2 were detected in the 100 cases tested. Mutations of p53 were found in 10/100 cases without any significant association with clinical stage. Deletions of 6q were present in 4/100 cases. Overall, our data indicate that: 1) contrary to previous reports, Bcl-1 and Bcl-2 rearrangements are not involved in CD5+ B-CLL pathogenesis and 2) p53 mutations are present in 10% of cases at all stages of the disease.