Post-transplant Lymphoproliferative Disorders: Implications for Acquired Immunodeficiency Syndrome-Associated Malignancies

Post-transplant lymphoproliferative disorders (PTLDs) comprisea histologic spectrum, ranging from hyperplastic-appearing lesionsto frank non-Hodgkin's lymphoma or multiple myeloma histology.Multiple clones may coexist, each representing a discrete lymphomagenicevent, a situation that is unique to immunodeficiency states.The incidence varies from 1% in renal recipients to 5% in heartrecipients, but can be markedly increased by the use of anti-T-celltherapies or by T-cell depletion in bone marrow transplantation.PTLD continues to arise, even many years after transplantation,and late T-cell lymphomas have recently been recognized. PretransplantEpstein-Barr virus (EBV) seronegativity increases risk to ashigh as 30%–50%. PTLD has a highly variable clinical picture;certain patterns are, however, seen. Reversibility of PTLD withreduction in immunosuppressives has long been recognized. Predictingreversibility has been difficult. The presence or absence ofbcl-6 mutations has recently been identified as being of predictivevalue. Surgical resection can be curative. Cytotoxics, althoughproblematic, can also be curative. Long-term remission has beenachieved with anti CD21 and CD24 antibodies; efficacy has beenreported for interferon alfa and for rituximab. In vitro expandedEBV-specific T cells have been effective as treatment and asprophylaxis in the setting of bone marrow transplantation. EBVviral load measured in blood appears to associate with the emergenceof PTLD and may facilitate prophylactic studies. PTLD is a modelof immunodeficiency-related EBV lymphomagenesis. Pathogenetic,therapeutic, and prophylactic insights gained from the studyof PTLD are likely to be applicable to the acquired immunodeficiencysyndrome setting.     

Myeloablative chemotherapy for recurrent aggressive oligodendroglioma

The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving aggressively at recurrence were eligible for this study. Only complete responders or major partial responders (75 % reduction in tumor size) to induction chemotherapy--either intensive-dose procarbazine, lomustine, and vincristine or cisplatin plus etoposide-could receive high-dose thiotepa (300 mg/m2/day for 3 days) followed by hematopoietic reconstitution using either bone marrow or peripheral blood stem cells. Thirty-eight patients began induction chemotherapy and 20 (10 men, 10 women; median age 46 years; median Karnofsky score 80) received high-dose thiotepa. For the high-dose group, the median event-free, progression-free, and overall survival times from recurrence were 17, 20, and 49 months, respectively. Tumor control in excess of 2 years was observed in 6 patients (30%). Four patients (20%) are alive and tumor free 27 to 77 months (median, 42 months) from the start of induction therapy; however, fatal treatment-related toxicities also occurred in 4 patients (20%). Three patients died as a result of a progressive encephalopathy which, in 2 instances, was accompanied by a wasting syndrome; 1 patient died as a consequence of an intracerebral (intratumoral) hemorrhage. Fatal toxicities occurred in patients with pretreatment Karnofsky scores of 60 or 70. High-dose thiotepa to consolidate response was a disappointing treatment strategy for patients with recurrent aggressive oligodendroglial neoplasms, although several patients had durable responses. Moreover, as prescribed, high-dose thiotepa had significant toxic effects in previously irradiated patients, especially those with poorer performance status.     

Long-term reendothelialization of excimer laser-assisted nonocclusive anastomoses compared with conventionally sutured anastomoses in pigs

OBJECT: In contrast to conventional anastomosis methods, the excimer laser-assisted nonocclusive anastomosis (ELANA) technique involves a platinum ring and intima-adventitia apposition with a rim of medial and adventitial layers exposed to the bloodstream. The authors assessed the reendothelialization of porcine carotid arteries through ELANA compared with conventional anastomosis by using scanning electron microscopy. METHODS: In 28 pigs a bypass with one ELANA and one conventional anastomosis was made on the left common carotid artery. All patent anastomoses were evaluated intraoperatively with the aid of an ultrasonographic flowmeter and postoperatively by using scanning electron microscopy at 2 weeks, 2 months, 3 months, and 6 months thereafter. Twenty-four of 28 bypasses (48 of 56 end-to-side anastomoses) were fully patent at the time of evaluation. On scanning electron microscopic evaluation of the bypasses, all 48 patent anastomoses showed complete reendothelialization, including all 24 ELANAs in which the endothelium covered the rim and the laser-ablated edge completely. No endothelial difference was observed between conventional anastomoses and ELANAs, aside from the obvious anatomical differences like the platinum ring, which had been completely covered with endothelium. At 6 months postsurgery, remodeling of the ELANA was observed, leaving the ring covered with a layer of endothelium as the most narrow part of the anastomosis. CONCLUSIONS: In long-term experiments, ELANA allows reendothelialization comparable to that achieved with conventional anastomosis. Considering its nonocclusive and high-flow characteristics, the ELANA technique is preferable in cerebral revascularization procedures.     

Pathological internal mammary lymph nodes in secondary and tertiary deep inferior epigastric perforator flap breast reconstructions

Use of internal mammary vessels during breast reconstruction provides information on part of the internal mammary chain lymph nodes (LNs). It was evaluated whether our current practice of screening should be changed to identify those delayed breast reconstruction patients with tumor-positive internal mammary nodes (IMNs) and whether breast reconstruction should be continued, in case suspicious IMNs were found intraoperatively. From February 2002 to December 2004, 81 patients had received 98 deep inferior epigastric perforator flaps for delayed breast reconstruction. Prospectively collected data for suspicious internal mammary LNs were evaluated. In 13 patients (16%) who had received a delayed breast reconstruction, macroscopically suspicious LNs were detected in the course of the internal mammary chain. Three patients (4%) had a pathologic diagnosis of malignancy, which was found to match their primary tumor. No relationship between positive internal mammary chain LNs and location of the primary tumor, TNM-stage, or previously administered adjuvant therapy was found. Suspicious internal mammary chain LNs found during recipient vessel dissection for breast reconstruction can have important consequences for treatment of malignant disease in individual patients. Presented data do not support changing the current perioperative approach of delayed breast reconstruction.     

Spatial interference during bimanual coordination: differential brain networks associated with control of movement amplitude and direction

Bimanual interference emerges when spatial features, such as movement direction or amplitude, differ between limbs, as indicated by a mutual bias of limb trajectories. Although first insights into the neural basis of directional interference have been revealed recently, little is known about the neural network associated with amplitude interference. We investigated whether amplitude versus directional interference activates differential networks. Functional magnetic resonance imaging (fMRI) was applied while subjects performed cyclical, bimanual joystick movements with either the same vs. different amplitudes, directions, or both. The kinematic analysis confirmed that subjects experienced amplitude interference when they moved with different as compared to the same amplitude, and directional interference when they moved along different as compared to the same direction. On the brain level, amplitude and directional interference both resulted in activation of a bilateral superior parietal-premotor network, which is known to contribute to sensorimotor transformations during goal-directed movements. Interestingly, amplitude but not directional interference exclusively activated a bilateral network containing the dorsolateral prefrontal cortex, anterior cingulate, and supramarginal gyrus, which was shown previously to contribute to executive functions. Even though the encoding of amplitude and directional information converged and activated the same neural substrate, our data thus show that additional and partly independent mechanisms are involved in bimanual amplitude as compared to that in directional control.     

The role of directional compatibility in assembling coordination patterns involving the upper and lower limb girdles and the head

The role of directional compatibility was investigated during the production of in-phase and anti-phase coordination patterns involving the four limbs as well as the head. Our first aim was to compare the quality of interlimb coordination between concordant and discordant coordination patterns across girdles at different cycling frequencies. Concordant implied adoption of either the in-phase or anti-phase coordination mode across both girdles whereas discordant implied a combination of both modes. The second aim was to study the effect of periodic head movements upon the assembling of a coordinative synergy among the limbs. Findings revealed that concordant coordination modes were produced with higher accuracy and consistency than discordant coordination modes and this effect was more distinct at higher cycling frequencies. Inclusion of head movements was found to destabilize in-phase coordination but stabilize anti-phase coordination patterns, particularly during discordant conditions at higher cycling frequencies. This observation contrasts with previous findings in which anti-phase modes have invariably been shown to be more vulnerable to experimental perturbations than in-phase modes. The findings are discussed within the context of the coalition of egocentric and allocentric constraints during multilimb coordination and the role of direction as an organizing principle in movement control.     

Parieto-premotor areas mediate directional interference during bimanual movements

In bimanual movements, interference emerges when limbs are moved simultaneously along incompatible directions. The neural substrate and mechanisms underlying this phenomenon are largely unknown. We used functional magnetic resonance imaging to compare brain activation during directional incompatible versus compatible bimanual movements. Our main results were that directional interference emerges primarily within superior parietal, intraparietal and dorsal premotor areas of the right hemisphere. The same areas were also activated when the unimanual subtasks were executed in isolation. In light of previous findings in monkeys and humans, we conclude that directional interference activates a parieto-premotor circuit that is involved in the control of goal-directed movements under somatosensory guidance. Moreover, our data suggest that the parietal cortex might represent an important locus for integrating spatial aspects of the limbs' movements into a common action. It is hypothesized to be the candidate structure from where interference arises when directionally incompatible movements are performed. We discuss the possibility that interference emerges when computational resources in these parietal areas are insufficient to code two incompatible movement directions independently from each other.     

Exercise programs for older men: mode and intensity to induce the highest possible health-related benefits

BACKGROUND: Although health-related benefits of fitness training in older men are well established, it is not clear yet which mode and intensity of a exercise program is most effective. This study addresses whether the combination of endurance (ED) and resistance training in older men have supplementary health-related benefits in addition to profits attained through endurance training alone. Additionally, effects of moderate- and low-intensity resistance training are compared. METHODS: Men, 55-75 years of age, were randomly assigned to a control group (N = 13) or one of three exercise groups (20 weeks, two to three times per week): endurance plus moderate resistance (MR) training (N = 22), endurance plus low resistance (LR) training (N = 22) and endurance training only (N = 22). Cardiovascular (CV) risk factors, muscular fitness and postural control were assessed before and after training. RESULTS: All exercise groups revealed significant (P < 0.05) improvements in resting heart rate, work capacity and recovery, waist girth, insulin response and knee-extensor strength with no differences among groups. Body composition, resting metabolic rate (RMR), VO2peak and postural control did not change in exercise groups. CONCLUSION: In older men, a fitness program consisting of 20 weeks endurance training combined with resistance training is equally effective as endurance training alone. Moderate vs. low resistance training added to endurance training yields similar health-related benefits.