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.     

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.     

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).     

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.     

A newborn with multiple fractures as first presentation of infantile myofibromatosis.

Pathological fractures occur in infancy from a variety of causes, but are a rare condition during neonatal period. We describe the case of a male newborn with a metaphyseal fracture of femur and multiple lytic lesions, diagnosed as infantile myofibromatosis.     

Expression of p170 protein in multiple myeloma: a clinical study.

The expression of the p170 multidrug resistance protein by bone marrow plasma cells (BMPC) was assessed at clinical presentation in 53 patients with multiple myeloma (MM) using the C219 monoclonal antibody. Twenty-two of the 53 (41 per cent) patients had variable aliquots (1-60 per cent, median = 6 per cent) of p170+ BMPC by immunocytochemistry. Five of 10 patients studied using bivariate flow cytometry had both diploid and hyperdiploid (DNA index ranged from 1.2 to 1.5) BMPC with hyperdiploid clones having significantly greater p170 expression than diploid ones. Of the 37 patients evaluated for a response, 20 (54 per cent) had responded to induction chemotherapy. The presence of p170+ BMPC was a negative indicator for achieving response. The response rate was 75 per cent for p170- and 25 per cent for p170+ cases (p < 0.01), with no difference on the basis of treatment schedule (melphalan and prednisone, 24 patients; peptichemio, vincristine and prednisone, 13 patients). No difference in response and survival duration was found between p170+ and p170- patients. In six of nine patients studied both at diagnosis and following induction chemotherapy the p170+ BMPC% increased irrespective of the type of treatment or outcome.     

Treatment of neuroblastoma with 131I-metaiodobenzylguanidine

Seven patients with neuroblastoma (six children and one adult) were treated with therapeutic doses of high specific activity 131I-metaiodobenzylguanidine (131I-MIBG). Six patients were in stage IV and unresponsive to conventional treatment. One patient, in stage III, was treated at diagnosis, an approach never previously reported. Single doses of 131I-MIBG varying from 70 to 184 mCi split into two parts were administered by slow i.v. infusion (4 to 8 hours) at 2- to 4-day intervals. The following results were obtained in the six evaluable patients: two patients showed transient stabilization of the disease; three had an objective response, with shrinking of the primary tumor and/or regression of the metastatic lesions. Of these three patients, two suffered relapses at 2 and 7 months, respectively, from the first course of MIBG. The third patient, in whom the residual disease almost completely disappeared following MIBG therapy, is still alive in complete remission after autologous bone marrow transplantation with a follow-up of 14 months. The single patient treated at diagnosis showed a dramatic response to a relatively low dosage of MIBG, with histologically proved disappearance of the tumor mass. Our data indicate that MIBG may be useful in the treatment of neuroblastoma unresponsive to conventional chemotherapy. The complete response observed in the patient treated at diagnosis suggests that the full potentiality of MIBG therapy should be explored in untreated patients.     

Natural killer (NK) cell generation in bone marrow cultures: role of IL-1 alpha.

Previous studies have demonstrated that IL-2 is able to induce the development of NK cells from bone marrow (BM) cultures, and that other cytokines acted synergistically with IL-2 in determining an increase of NK cells development. The addition of TNF alpha greatly enhanced the IL-2-mediated induction of NK effector. However, the effect of IL-2 and TNF alpha could be due to direct stimulation of NK progenitors, or to the endogenous production of other factors, which are then responsible of the development of NK cells. As results show that the mRNA specific for IL-1 alpha could be detected in BM cells cultured with IL-2, but not in that supplemented with IL-2 + TNF alpha, it would seem that this lymphokine plays a role only in IL-2-dependent development of NK cells. Studies with Ab anti-IL-1 alpha, showed that the antibody abrograted the IL-2-driven generation of NK cells, but did not affect the NK differentiation induced by IL-2 + TNF alpha. The cytotoxic cells generated by IL-2 or by IL-2 + TNF alpha had the phenotype of mature NK cells including expression of NK 1.1, asialo GM1, Lyt-5, LFA-1, and Thy-1. These data suggest that in spite of phenotypical and morphological similarity of the cells generated with IL-2 or IL-2 + TNF alpha, the endogenous production of IL-1 alpha, appears functionally important only for the differentiation of NK cells induced by IL-2 alone.