Simultaneous Doppelgänger and limb amputation impression in right frontal opercular stroke.

A case is described of a patient who presented almost simultaneously the impression that his left arm was amputated and the feeling of the presence of his invisible Doppelgänger. While these body scheme disorders have both been described after (right) parietal lesions, a right frontal opercular ischaemic stroke was found in the neurological work up. Diffusion tensor imaging showed that the stroke involved the ventral bundle of the superior longitudinal fasciculus that connects the parietal to the frontal lobe. The unusual clinical presentation of this frontal lesion may have been due to a 'diaschisis'-like phenomenon via the superior longitudinal fasciculus.

A dystroglycan mutation associated with limb-girdle muscular dystrophy.

Dystroglycan, which serves as a major extracellular matrix receptor in muscle and the central nervous system, requires extensive O-glycosylation to function. We identified a dystroglycan missense mutation (Thr192→Met) in a woman with limb-girdle muscular dystrophy and cognitive impairment. A mouse model harboring this mutation recapitulates the immunohistochemical and neuromuscular abnormalities observed in the patient. In vitro and in vivo studies showed that the mutation impairs the receptor function of dystroglycan in skeletal muscle and brain by inhibiting the post-translational modification, mediated by the glycosyltransferase LARGE, of the phosphorylated O-mannosyl glycans on α-dystroglycan that is required for high-affinity binding to laminin.

A new way of quantifying dominant upper-limb mobility in healthy and painful shoulders

Introduction: Quantification of daily upper-limb activity is determinant in the evaluation of shoulder surgery. For a number of shoulder diseases, roblems in performing daily activities have been expressed in terms of upper-limb usage. Althought many instruments measure upper-limb movements, there is no accepted standard or widely used objective measure and no device to differenciate left or right shoulder usage. We present an objective method to measure the mobility and quantify the usage of dominant and healthy or painfull shoulder movement during daily life. Methods: 12 patients with unilateral pathological shoulder (rotator cuff disease) are compared to 18 control subjects (10 right and 8 left handed). Both SST and DASH questionnaires were completed by each one. Three inertial miniature modules including triaxial gyroscopes and accelerometers were fixed on the dorsal side of both humerus, and on the thorax. An ambulatory datalogger have recorded the signals during one day. Results: We observed that right handed healthy subjects used 18% and 26% more their dominant shoulder during respectively stand and sit postures while left handed subjects used 8% and 18% more their left side. In walking periods, shoulder mobility was quite alike for both sides. Patients affected on their dominant arm (PD group) mostly used their non-dominant side (respectively 5% and 9% during stand and sit). For the patients affected on their non-dominant shoulder (PND group), this difference is respectively 28% and 26%. Moreover, we can note that, during walking periods, a difference can be observed (on the contrary to controls). Patients used 13% and 15% more their nonpathologic side respectively for PD and PND groups. Conclusion: Inertial sensors, during long-term ambulatory monitoring of upper limbs, can quantify the difference between dominant and nondominant sides. Patients used more their non affected shoulder during daily life. For the PD group, the difference with control can be shown during walking. These results are very encouraging for future evaluation of patients with shoulder injuries since it can provide an objective evaluation of the shoulder mobility and of the treatment outcome during daily life.

Isolated limb perfusion with tumor necrosis factor and melphalan for non-resectable soft tissue sarcomas : long-term results on efficacy and limb salvage in a selected group of patients

Rapport de synthèse : Introduction : La perfusion isolée de membre (isolated limb perfusion, ou ILP) par TNF-alpha et melphalan, utilisés en association, est une stratégie de prise en charge chirurgicale des sarcomes non opérables des extrémités. Elle a été en partie développée au CHUV dans les années 1990, sous l'impulsion du Professeur F. Lejeune, ancien Chef du Service d'oncologie médicale (CePO). Les résultats des 31 premiers patients ont été publiés en 2000 dans l'European Journal of Surgical Oncology. Les données dans la littérature manquant sur les résultats à long terme, nous avons revu tous les patients traités au CHUV depuis 1992 pour tenter des de déterminer ces résultats à long terme, en se focalisant sur l'efficacité du traitement, symbolisée par le taux de sauvetage de membres, autrement condamnés à l'amputation ou à une chirurgie mutilante. Matériel et méthode : Etude rétrospective. De 1992 à mars 2006, 51 patients ont été traités par ILP dans notre institution, certains à deux reprises (58 ILP au total). Quatre-vingt-huit pour cent présentaient un sarcome de haut grade de malignité, et 84% une tumeur localement avancée (T2b NO Mo ou plus). Résultats : Le follow-up moyen est de 38.9 mois (4-159, médiane 22 mois), on note 21 % de complications immédiates et 23% de complications tardives ou chroniques. Une réponse complète (nécrose totale ou disparition de la tumeur) a été observée dans 25% des cas, une réponse partielle (>50% de nécrose ou de diminution de taille tumorale) dans 42%, une stabilité de la maladie dans 14% et une progression tumorale dans 14%. Un traitement adjuvant a été entrepris dans 31 % des cas, une résection des résidus tumoraux a pu être effectuée chez 65% des patients. On note un taux de récidive locale de 35% (après 20,3 mois en moyenne) et un taux de récidive à distance de 45% (après 13,4 mois en moyenne). Le disease-free survival est de 14,9 mois et la survie à 5 ans de 43,5%. Le taux d'amputation s'élève à 24%. Conclusion : La perfusion isolée de membre est un traitement grevé d'un taux élevé de complications, mais il peut étre entrepris dans les sarcomes les plus sévères avec un succès significatif. Ainsi, dans notre série, une chirurgie mutilante (en général l'amputation) a pu être épargnée à 76% des patients.

Can a Halo CME from the limb be geoeffective?

The probability for a halo coronal mass ejection (CME) to be geoeffective is assumed to be higher the closer the CME launch site is located to the solar central meridian. However, events far from the central meridian may produce severe geomagnetic storms, like the case in April 2000. In this work, we study the possible geoeffectiveness of full halo CMEs with the source region situated at solar limb. For this task, we select all limb full halo (LFH) CMEs that occurred during solar cycle 23, and we search for signatures of geoeffectiveness between 1 and 5 days after the first appearance of each CME in the LASCO C2 field of view. When signatures of geomagnetic activity are observed in the selected time window, interplanetary data are carefully analyzed in order to look for the cause of the geomagnetic disturbance. Finally, a possible association between geoeffective interplanetary signatures and every LFH CME in solar cycle 23 is checked in order to decide on the CME's geoeffectiveness. After a detailed analysis of solar, interplanetary, and geomagnetic data, we conclude that of the 25 investigated events, there are only four geoeffective LFH CMEs, all coming from the west limb. The geoeffectiveness of these events seems to be moderate, turning to intense in two of them as a result of cumulative effects from previous mass ejections. We conclude that ejections from solar locations close to the west limb should be considered in space weather, at least as sources of moderate disturbances.

Resuming motor vehicle driving following orthopaedic surgery or limb trauma.

Following elective orthopaedic surgery or the treatment of a fracture, patients are temporarily unable to drive. This loss of independence may have serious social and economic consequences for the patient. It is therefore essential to know when it is safe to permit such patients to return to driving. This article, based upon a review of the current literature, proposes recommendations of the time period after which patients may safely return to driving. Practical decisions are made based upon the type of surgical intervention or fracture. Swiss legislation is equally approached so as to better define the decision.

The αVβ3/αVβ5 integrin inhibitor cilengitide augments tumor response to melphalan isolated limb perfusion in a sarcoma model.

Isolated limb perfusion (ILP) with melphalan and tumor necrosis factor (TNF)-α is used to treat bulky, locally advanced melanoma and sarcoma. However, TNF toxicity suggests a need for better-tolerated drugs. Cilengitide (EMD 121974), a novel cyclic inhibitor of alpha-V integrins, has both anti-angiogenic and direct anti-tumor effects and is a possible alternative to TNF in ILP. In this study, rats bearing a hind limb soft tissue sarcoma underwent ILP using different combinations of melphalan, TNF and cilengitide in the perfusate. Further groups had intra-peritoneal (i.p.) injections of cilengitide or saline 2 hr before and 3 hr after ILP. A 77% response rate (RR) was seen in animals treated i.p. with cilengitide and perfused with melphalan plus cilengitide. The RR was 85% in animals treated i.p. with cilengitide and ILP using melphalan plus both TNF and cilengitide. Both RRs were significantly greater than those seen with melphalan or cilengitide alone. Histopathology showed that high RRs were accompanied by disruption of tumor vascular endothelium and tumor necrosis. Compared with ILP using melphalan alone, the addition of cilengitide resulted in a three to sevenfold increase in melphalan concentration in tumor but not in muscle in the perfused limb. Supportive in vitro studies indicate that cilengitide both inhibits tumor cell attachment and increases endothelial permeability. Since cilengitide has low toxicity, these data suggest the agent is a good alternative to TNF in the ILP setting.

Isolated limb perfusion: distinct tourniquet and tumor necrosis factor effects on the early hemodynamic response.

HYPOTHESIS: Recent evidence indicates that tumor response rates after isolated limb perfusion (ILP) are improved when tumor necrosis factor (TNF) is added to the locoregional perfusion of high doses of chemotherapy. Other factors, related to the patient or the ILP procedure, may interfere with the specific role of TNF in the early hemodynamic response after ILP with TNF and high-dose chemotherapy. DESIGN: Case-control study. SETTING: Tertiary care university hospital. PATIENTS: Thirty-eight patients with a locoregionally advanced tumor of a limb treated by ILP with TNF and high-dose chemotherapy (TNF group) were compared with 31 similar patients treated by ILP with high-dose chemotherapy alone (non-TNF group). INTERVENTIONS: Swan-Ganz catheter hemodynamic recordings, patients' treatment data collection, and TNF and interleukin 6 plasma level measurements at regular intervals during the first 36 hours following ILP. MAIN OUTCOME MEASURES: Hemodynamic profile and total fluid and catecholamine administration. RESULTS: In the TNF group, significant changes were observed (P<.006): the mean arterial pressure and the systemic vascular resistance index decreased, and the temperature, heart rate, and cardiac index increased. These hemodynamic alterations started when the ILP tourniquet was released (ie, when or shortly after the systemic TNF levels were the highest). The minimal mean arterial pressure, the minimal systemic vascular resistance index, the maximal cardiac index, the intensive care unit stay, and the interleukin 6 maximal systemic levels were significantly (P<.001 for all) correlated to the log(10) of the systemic TNF level. In the non-TNF group, only a brief decrease in the blood pressure following tourniquet release and an increase in the temperature and in the heart rate were statistically significant (P<.006). Despite significantly more fluid and catecholamine administration in the TNF group, the mean arterial pressure and the systemic vascular resistance index were significantly (P<.001) lower than in the non-TNF group. CONCLUSIONS: Release of the tourniquet induces a blood pressure decrease that lasts less than 1 hour in the absence of TNF and that is distinct from the septic shock-like hemodynamic profile following TNF administration. The systemic TNF levels are correlated to this hemodynamic response, which can be observed even at low TNF levels.

Foot skin blood flow following infrainguinal revascularization for critical lower limb ischemia.

INTRODUCTION: The aim of this study was to assess the blood flow in the feet before and after lower limb revascularization using laser Doppler imaging (LDI). METHODS: Ten patients with critical lower limb ischemia were prospectively enrolled from June to October 2004. All patients underwent successful unilateral surgical interventions including above-knee bypass, distal bypass and endarterectomy. Skin blood flow (SBF) over the plantar surface of both forefeet and heels was measured by LDI 24h before and 10 days after revascularization, expressed in perfusion units (PU), and reported as mean+/-SD. RESULTS: Measurements in the forefoot and heel were similar. Before revascularization mean SBF was significantly lower in the ischemic foot (130+/-71 PU) compared to the contralateral foot (212+/-68 PU), p<0.05. After revascularization a significant increase of the SBF in the forefoot (from 135+/-67 to 202+/-86 PU, p=0.001) and hindfoot (from 148+/-58 to 203+/-83, p=0.001) was observed on the treatment side. However, a large decrease of the SBF was seen in forefoot and hindfoot on the untreated side (from 250+/-123 PU to 176+/-83 and from 208+/-116 to 133+/-40, p=0.001, respectively). CONCLUSION: This study confirms the benefits of revascularization in patients with nonhealing foot lesions due to critical limb ischemia. A significant increase of the SBF was observed on the treatment side. However, an unexpected decrease was observed on the untreated side.

Isolated limb perfusion with tumor necrosis factor and melphalan for non-resectable soft tissue sarcomas: long-term results on efficacy and limb salvage in a selected group of patients

Background And Objectives: Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a limb salvage therapy for non-resectable soft tissue sarcomas (STS) of the extremities. It is indicated for patients for whom amputation or debilitating surgery is the only alternative. It can be used either as an exclusive therapy (in palliation) or as a neo-adjuvant treatment, followed by marginal resection of tumor remnants with minimal functional impairment. Methods: Between February 1992 and March 2006, 57 TM-ILPs were performed on 51 patients with 88% high grade and 84% advanced stage tumors. Results: Mean follow-up is 38.9 months (4-159, median 22 months). Twenty-one percent patients had significant early complications, with 3 major re-operations, and 23% suffered long-lasting complications. Complete response was observed in 25%, partial response in 42%, stable disease in 14% and progressive disease in 14%. Resection of the tumor remnants was possible in 65%. A complementary treatment was necessary in 31%, mostly radiation therapy. A local recurrence was observed in 35%, after a mean of 20.3 months (2-78), and distant relapse was seen in 45%, after a mean of 13.4 months (5-196). Mean Disease-free survival was 14.9 months, and overall 5-year-survival 43.5%. Amputation rate at 5 years was 24%. Conclusions: TM-ILP is a conservative treatment with a high complications rate, but it can be successful even for the most severe STS of extremities. As a consequence the limb can be spared from amputation or debilitating surgery on the long term in about 75% of patients

p53 status correlates with histopathological response in patients with soft tissue sarcomas treated using isolated limb perfusion with TNF-alpha and melphalan.

BACKGROUND: Recombinant tumor necrosis factor-alpha (TNF-alpha) combined to melphalan is clinically administered through isolated limb perfusion (ILP) for regionally advanced soft tissue sarcomas of the limbs. In preclinical studies, wild-type p53 gene is involved in the regulation of cytotoxic action of TNF-alpha and loss of p53 function contributes to the resistance of tumour cells to TNF-alpha. The relationship between p53 status and response to TNF-alpha and melphalan in patients undergoing ILP is unknown. PATIENTS AND METHODS: We studied 110 cases of unresectable limbs sarcomas treated by ILP. Immunohistochemistry was carried out using DO7mAb, which reacts with an antigenic determinant from the N-terminal region of both the wild-type and mutant forms of the p53 protein, and PAb1620mAb, which reacts with the 1620 epitope characteristic of the wild-type native conformation of the p53 protein. The immunohistochemistry data were then correlated with various clinical parameters. RESULTS: P53DO7 was found expressed at high levels in 28 patients, whereas PAb1620 was negative in 20. The tumours with poor histological response to ILP with TNF-alpha and melphalan showed significantly higher levels of p53-mutated protein. CONCLUSIONS: Our results might be a clue to a role of p53 protein status in TNF-alpha and melphalan response in clinical use.

A downstream mediator in the growth repression limb of the jasmonate pathway.

Wounding plant tissues initiates large-scale changes in transcription coupled to growth arrest, allowing resource diversion for defense. These processes are mediated in large part by the potent lipid regulator jasmonic acid (JA). Genes selected from a list of wound-inducible transcripts regulated by the jasmonate pathway were overexpressed in Arabidopsis thaliana, and the transgenic plants were then assayed for sensitivity to methyl jasmonate (MeJA). When grown in the presence of MeJA, the roots of plants overexpressing a gene of unknown function were longer than those of wild-type plants. When transcript levels for this gene, which we named JASMONATE-ASSOCIATED1 (JAS1), were reduced by RNA interference, the plants showed increased sensitivity to MeJA and growth was inhibited. These gain- and loss-of-function assays suggest that this gene acts as a repressor of JA-inhibited growth. An alternative transcript from the gene encoding a second protein isoform with a longer C terminus failed to repress jasmonate sensitivity. This identified a conserved C-terminal sequence in JAS1 and related genes, all of which also contain Zim motifs and many of which are jasmonate-regulated. Both forms of JAS1 were found to localize to the nucleus in transient expression assays. Physiological tests of growth responses after wounding were consistent with the fact that JAS1 is a repressor of JA-regulated growth retardation.