Spinal cord stimulation in non-reconstructable critical limb ischemia: a retrospective study of 71 cases.

BACKGROUND: Spinal cord stimulation (SCS) is a therapeutic option for patients with a peripheral arterial disease with critical limb ischemia (CLI) and consequent ischemic rest pain. Neuromodulation is chosen when vascular reconstruction is not possible or failed. Data about the effect of SCS over limb salvage rates are dissonant. METHOD: We report on a retrospective cohort of CLI patients who were implanted with SCS systems between July 2010 and December 2013 in a single center. Major amputation, postoperative complications, and death were recorded. RESULTS: Seventy-two CLI patients underwent SCS implantation, with 35 of them classified as non-reconstructable and 37 with previous but failed or only partially successful vascular procedures. A total of 21 subjects were at Fontaine's stage III (29.2%), and the remaining 51 were at stage IV (70.8%). In total, 26.4% of the patients had diabetes (n = 19), two of them at Fontaine's stage III. The mean follow-up was 17.1 ± 10.5 months. At the last follow-up, 59.2% of all patients (42/71), 85.7% of Fontaine's stage III (18/21), 48.0% of Fontaine's stage IV (24/50), and 52.6% of diabetic patients (10/19) were alive without major amputation. The probability of limb survival at 12 months was 72% for all patients, 94% for Fontaine's stage III, 62% for Fontaine's stage IV, and 61% for diabetic patients. The probability of survival at 12 months for patients who underwent major limb amputation (n = 25) was 86% with a mean survival time of 31.03 ± 4.63 months. CONCLUSIONS: Non-reconstructable CLI patients treated with SCS can achieve meaningful clinical outcomes with few procedure-related complications. The therapy may be more beneficial in patients classified as Fontaine's Stage III.

Measuring Topological Invariants in a Polaritonic Analog of Graphene.

Topological materials rely on engineering global properties of their bulk energy bands called topological invariants. These invariants, usually defined over the entire Brillouin zone, are related to the existence of protected edge states. However, for an important class of Hamiltonians corresponding to 2D lattices with time-reversal and chiral symmetry (e.g., graphene), the existence of edge states is linked to invariants that are not defined over the full 2D Brillouin zone, but on reduced 1D subspaces. Here, we demonstrate a novel scheme based on a combined real- and momentum-space measurement to directly access these 1D topological invariants in lattices of semiconductor microcavities confining exciton polaritons. We extract these invariants in arrays emulating the physics of regular and critically compressed graphene where Dirac cones have merged. Our scheme provides a direct evidence of the bulk-edge correspondence in these systems and opens the door to the exploration of more complex topological effects, e.g., involving disorder and interactions.

Dynamical Solitons and Boson Fractionalization in Cold-Atom Topological Insulators.

We study the Z_{2} Bose-Hubbard model, a chain of interacting bosons the tunneling of which is dressed by a dynamical Z_{2} field. The interplay between spontaneous symmetry breaking (SSB) and topological symmetry protection gives rise to interesting fractional topological phenomena when the system is doped to certain incommensurate fillings. In particular, we hereby show how topological defects in the Z_{2} field can appear in the ground state, connecting different SSB sectors. These defects are dynamical and can travel through the lattice carrying both a topological charge and a fractional particle number. In the hardcore limit, this phenomenon can be understood through a bulk-defect correspondence. Using a pumping argument, we show that it survives also for finite interactions, demonstrating how boson fractionalization induced by topological defects can occur in strongly correlated bosonic systems. Our results indicate the possibility of observing this phenomenon, which appears for fermionic matter in solid-state and high-energy physics, using ultracold atomic systems.

Tip enhanced Raman spectroscopy imaging of opaque samples in organic liquid.

Implementation of Tip Enhanced Raman Spectroscopy in liquid is still a challenge. We demonstrate herein its feasibility in an upright illumination/collection configuration. Through a thin layer of organic solvent covering the sample, laser focussing on the tip is possible, enabling TERS imaging in liquid.

Role of the lean body mass and of pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of sunitinib in cancer patients.

INTRODUCTION: Sunitinib is a multikinase inhibitor active in various cancers types including renal cancers and endocrine tumors. The study analyzed the influence of the lean body mass (LBM) and of pharmacogenetic variants on the exposure to sunitinib and its active metabolite, SU12662, and on sunitinib toxicity and clinical activity. MATERIALS AND METHODS: Exposure to sunitinib and SU12662 was assessed on days 10 and 21 during the first treatment cycle. Acute toxicity was graded using the NCI 4.0 CTCAE ver. 4.0. The LBM and 14 common single nucleotide polymorphisms in the CYP3A4/3A5, NR1I2, NR1I3, ABCB1, and ABCG2 genes were analyzed according to the drug exposure at day 10. Determinants (including sunitinib exposure and pharmacogenetic variants) for toxicities were assessed, as well as the relationship between drug exposure and survival in renal cancer patients. RESULTS: Ninety-two patients (60 % with renal cancer) were assessable for pharmacokinetics, toxicity and survival, and 66 for genetic analysis. The LBM (p < 0.0001) and a polymorphism in the ABCG2 transporter (421C>A) (p = 0.014) were two independent parameters accounting for the variability of composite (sunitinib + SU12662) exposure. Advanced age (OR = 1.47 [1.01-2.15], p = 0.048) and high sunitinib exposure (OR = 1.16 [1.05-1.28], p = 0.005) were independently associated with any grade ≥ 3 acute toxicity, and high SU12662 exposure was associated with grade ≥ 2 thrombocytopenia (OR = 1.27 [1.03-1.57], p = 0.028). A high composite area under the curve (AUC) >1,973 ng/mL∙h at day 21 was associated with a doubled survival (35.2 vs 16.7 months; log-rank p = 0.0051) in renal cancer patients. CONCLUSIONS: This study indicates that LBM and drug monitoring may be helpful in the management of sunitinib-treated patients.

HrpZ harpins from different Pseudomonas syringae pathovars differ in molecular interactions and in induction of anion channel responses in Arabidopsis thaliana suspension cells.

HrpZ, a type three secretion system helper protein from the plant-pathogen Pseudomonas syringae, can be recognized by many plants as a defence elicitor. Responses of Arabidopsis thaliana suspension cells to different HrpZ variants were studied by electrophysiological methods and cell death assay. Purified HrpZ originating from a compatible pathogen P. syringae pv. tomato DC3000 (HrpZ(Pto)) and incompatible P. syringae pv. phaseolicola (HrpZ(Pph)) both promoted Arabidopsis cell death. As an early response, both HrpZ variants induced an increase in time dependent K(+) outward rectifying current. In contrast, the effects of HrpZ proteins on anion currents were different: HrpZ(Pph) had no effect, and HrpZ(Pto) induced an anion current increase. This suggests that the observed responses of the K(+) channels and anion channels resulted from different and separable interactions and that the interaction implied in anion current modulation is host-specific. HrpZ(Pto) and HrpZ(Pph) also had a different sequence preference in phage display screen for peptide-binding. These peptides presumably represent a part of a putative target protein in the host, and HrpZ proteins of different P. syringae pathovars might have different binding specificities to match the allelic variation between plant species. Supporting the idea that the peptide-binding region of HrpZ is important for interactions with host cell components, we found that a mutation in that region changed the anion channel response of Arabidopsis cells.

Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice.

Sorafenib, a new oral multikinase inhibitor with antiangiogenic properties, has demonstrated preclinical and clinical activity against several tumor types. The aims of this study were to validate a method for the measurement of sorafenib in plasma from cancer patients, then to test this method in clinical practice. Following liquid-liquid extraction, the compounds were separated with gradient elution (on a C18 ultrasphere ODS column using a mobile phase of acetonitrile/20 mM ammonium acetate), then detected at 255 nm. The calibration was linear in the range 0.5-20 mg/L. Intra- and inter-assay precision was lower than 7 and 10%, respectively, at 0.5, 3 and 20 mg/L. Plasma sorafenib concentrations were measured in 22 cancer patients (99 samples). The mean trough sorafenib concentration (C(min)) and concentration at peak were 4.3+/-2.5 mg/L (n=68, CV=57.5%) and 6.2+/-3.0 mg/L (n=31, CV=47.5%), respectively. Mean sorafenib C(min) in eight patients who experienced grade 3 drug-related adverse events was approximately 1.5-fold greater than that observed in the remaining patients (7.7+/-3.6 mg/L vs. 4.4+/-2.4 mg/L, P=0.0083). In conclusion, the method was successfully used in routine practice to monitor plasma concentrations of sorafenib in cancer patients. Finally, large interindividual variability and higher exposure in patients experiencing severe toxicity support the need for therapeutic drug monitoring to ensure an optimal exposure to sorafenib.

An early Ca2+ influx is a prerequisite to thaxtomin A-induced cell death in Arabidopsis thaliana cells.

The pathogenicity of various Streptomyces scabies isolates involved in potato scab disease was correlated with the production of thaxtomin A. Since calcium is known as an essential second messenger associated with pathogen-induced plant responses and cell death, it was investigated whether thaxtomin A could induce a Ca2+ influx related to cell death and to other putative plant responses using Arabidopsis thaliana suspension cells, which is a convenient model to study plant-microbe interactions. A. thaliana cells were treated with micromolar concentrations of thaxtomin A. Cell death was quantified and ion flux variations were analysed from electrophysiological measurements with the apoaequorin Ca2+ reporter protein and by external pH measurement. Involvement of anion and calcium channels in signal transduction leading to programmed cell death was determined by using specific inhibitors. These data suggest that this toxin induces a rapid Ca2+ influx and cell death in A. thaliana cell suspensions. Moreover, these data provide strong evidence that the Ca2+ influx induced by thaxtomin A is necessary to achieve this cell death and is a prerequisite to early thaxtomin A-induced responses: anion current increase, alkalization of the external medium, and the expression of PAL1 coding for a key enzyme of the phenylpropanoid pathway.

[Short- and midterm effectiveness of a back school. Retrospective cohort study on 328 patients with chronic low back pain from 1997 to 2004]. / Efficacité à court- et moyen terme d'un programme d'école du dos. Etude de cohorte rétrospective réalisée sur 328 lombalgiques chroniques de 1997 à 2004.

OBJECTIVES: To assess the short- and midterm effects of a back school programme on patients with chronic low back pain. To determine positive factors to the effectiveness of back school. METHODS: A retrospective cohort study about 328 chronic low back pain patients who participated to back school from 1997 to 2004. One hundred and thirty-two patients had comparative study at six months. The descriptive study used the "before and after" method. Logistic regression analysis was performed to evaluate factors statistically associated with improvement of pain and functional, social and occupational status. RESULTS: The six months results showed effectiveness of back school on pain and functional status. The impact on quality of life was low. It made reduction of the period of sick leave but not recurrence of them. Predictors to effectiveness of back school were identified: to be young and to have regular physical activity. To be anxious, overweight and to receive worker's compensation were devafourable factors to effectiveness of back school. CONCLUSION: Even if the number of lost to follow up is high, these results are encouraging. A long-term follow-up is necessary to confirm the initial benefits of back school. We although have to assess the role of physical activity in mid-term effectiveness of this back school.

Fungal hypaphorine reduces growth and induces cytosolic calcium increase in root hairs of Eucalyptus globulus.

Root hairs are tubular cells resulting from a tip-localized growth in which calcium ions play a key role. Hypaphorine, an indole alkaloid secreted by the fungus Pisolithus microcarpus during the formation of ectomycorrhizae with the host plant Eucalyptus globulus, inhibits root hair tip growth. Hypaphorine-induced inhibition is linked to a transient depolarization of the plasma membrane and a reorganization of the actin and microtubule cytoskeletons. Here we investigated the activity of hypaphorine on calcium distribution in E. globulus root hairs with the ratiometric fluorochrome calcium indicator Indo-1. In 85% of actively growing root hairs, a significant but modest calcium gradient between the apex and the base was observed due to an elevated cytoplasmic calcium concentration at the apical tip. Following exposure to 1 mM hypaphorine, the apical and basal cytoplasmic Ca(2+) concentration increased in 70 and 77% of the hairs, respectively, 10 min after treatment. This led to a reduced calcium gradient in 81% of the cells. The hypothetical links between calcium concentration elevation, regulation of actin cytoskeleton dynamics, and root hair growth inhibition in response to hypaphorine treatment are discussed.

Mutations in the SPG3A gene encoding the GTPase atlastin interfere with vesicle trafficking in the ER/Golgi interface and Golgi morphogenesis.

Mutations in SPG3A causing autosomal dominant pure spastic paraplegia led to identification of atlastin, a new dynamin-like large GTPase. Atlastin is localized in the endoplasmic reticulum, the Golgi, neurites and growth cones and has been implicated in neurite outgrowth. To investigate whether it exerts its activity in the early secretory system, we expressed normal and mutant atlastin in cell culture. Pathogenic mutations in the GTPase domain interfered with the maturation of Golgi complexes by preventing the budding of vesicles from the endoplasmic reticulum, whereas mutations in other regions of the protein disrupted fission of endoplasmic reticulum-derived vesicles or their migration to their Golgi target. Atlastin, therefore, plays a role in vesicle trafficking in the ER/Golgi interface. Furthermore, atlastin partially co-localized with proteins of the p24/emp/gp25L family that regulate vesicle budding and trafficking in the early secretory pathway, and co-immunoprecipitated p24, suggesting a functional relationship that should be further explored.

A specific clinical pattern of camptocormia in Parkinson's disease.

BACKGROUND: Camptocormia, characterised by extreme forward flexion of the thoracolumbar spine and severe stooping in the supine position, seems to be prevalent in Parkinson's disease. OBJECTIVE: The aim of this study was to identify features of parkinsonian camptocormia and to describe the main clinical characteristics of patients with Parkinson's disease who develop the condition. METHODS: An extensive range of clinical, biochemical and imaging data were gathered for 23 patients with Parkinson's disease with camptocormia, notably including magnetic resonance imaging (MRI) of the brain and spine, electromyographic recordings of the paravertebral muscles and muscle biopsies. RESULTS: Camptocormia occurred in severe Parkinson's disease with axial predominance, motor fluctuations and dysautonomic symptoms. The condition was often associated with spondyloarthritic changes and pain. MRI showed paraspinal muscle signal abnormalities in five patients and fatty involution in seven patients. The seven patients had motor unit reductions on the spinal erector electromyogram. The MRI results for the girdle muscles were normal. Cranial MRI showed signal abnormalities for the basal ganglia in three patients. DISCUSSION: Various mechanisms may contribute to the development of parkinsonian camptocormia: dopaminergic depletion in Parkinson's disease induces functional changes in the organisation of the corticospinal and reticulospinal tracts, where dysfunction could contribute to axial rigidity. Furthermore, rigidity of the spinal flexion muscles could lead to under-use of the spinal extension muscles, which become progressively atrophic. Rigidity may also induce spinal deformations, leading to a neurogenic syndrome via compression of the spinal nerves. CONCLUSION: The screening and early management of camptocormia in Parkinson's disease is likely to be important for preventing axial disorders and spinal deformations.

Actin organization during eucalyptus root hair development and its response to fungal hypaphorine.

The fungus Pisolithus microcarpus establishes an ectomycorrhiza with Eucalyptus globulus. This symbiosis involves a fungal synthesis and secretion of hypaphorine, an indolic compound. Previous studies have shown that hypaphorine induces an alteration in the actin cytoskeleton of elongating root hairs and inhibits hair elongation. Using an alternative approved method, we analyzed the effects of hypaphorine on the E. globulus root hair cyto-architecture and actin configuration in more detail and provide new results. One mM hypaphorine stops root hair elongation within 20 min, and changes the hair cyto-architecture. Semi-quantitative analysis of the actin cytoskeleton before and after treatment with hypaphorine shows that hypaphorine induces a shift from fine F-actin to F-actin bundles in the sub-apex of the hair, which occurs first in the mid-plane of the cell. This creates a sub-apical cell centre free of filamentous actin, an actin configuration that differs from that during developmental growth arrest. The mechanism of action of hypaphorine is discussed.

[Parkinson's disease, progressive lumbar kyphosis and focal paraspinal myositis]. / Maladie de Parkinson, camptocormie et myosite focale paraspinale.

INTRODUCTION: The camptocormia (bent spine) is characterized by a severe forward flexion of the thoracolumbar spine which disappears in the supine position. Clinical case. We describe a typical case observed in a parkinsonian patient. The MRI, electromyogram and biopsy of the paraspinal muscles revealed a typical myositis pattern. DISCUSSION: This case, the sixth published to our knowledge, confirms that focal myositis is associated with the camptocormia in Parkinson's disease. Typically it is observed in male subjects, appearing 4 to 6 years after the onset of Parkinson's disease, in fluctuating patients treated by an association of L-Dopa and agonist. It appears quickly and becomes the most important symptom. Antiparkinsonian drugs are useless. CONCLUSION: This exceptional picture raises original pathophysiological and therapeutic questions. Systematic studies should be performed in order to detail the pathophysiological link between these 3 entities: Parkinson's disease, focal myositis and camptocormia.

[Treatment of ejaculation disorders by midodrine (Gutron) per os. Retrospective study of about 16 subjects]. / Prise en charge des troubles de l'éjaculation par chlorhydrate de midodrine (Gutron) per os. Etude rétrospective chez 16 sujets.

PURPOSE: We evaluate the efficiency and side effects of midodrine in the treatment of sperm transport disturbances. MATERIALS AND METHODS: This retrospective study concerned patients addressed in Andrologia Department between 1995 and 2002 for treatment of sperm transport disturbances by administration of Midodrine per os (from 2.5 to 20 mg). Anterograde and retrogrades ejaculates (in urine sample) were examined. RESULTS: Sixteen patients (middle age of 36 years) were included: 12 neurologic lesions (central or peripheral, with 3 diabetes), four post-surgical (urologic and digestive) ejaculatory incompetence. One patient obtained anterior and retrograde ejaculation, two patients obtained anterior ejaculation and six retrograde ejaculations by midodrine per os. This treatment was inefficient in eight subjects. Side effects were exceptional. DISCUSSION: We obtained anterior or retrograde ejaculation in half of our population. The success was more important in patients with central neurologic injuries, diabetes or post-surgical troubles. In peripheral neurologic injuries, midodrine per os (maximal dose of 20 mg) was ineffective. CONCLUSION: Our study demonstrates the efficiency and good tolerance of midodrine per os for treatment of sperm transport disturbances.

Intravenous iron administration does not significantly increase the risk of bacteremia in chronic hemodialysis patients.

BACKGROUND: Correction of iron deficiency is critical in chronic hemodialysis patients, and intravenous administration is superior to the oral route in this goal. Recently, concern was raised that intravenous iron administration might promote infection in dialysis patients. METHODS: We reviewed the data from a recent prospective study of 985 patients in which no link between iron therapy and bacteremia had been found. We tested the potential role of the administration route of the iron (intravenous vs. oral), the weekly amount of iron administered and the administration rate on the risk for bacteremia in these patients. RESULTS: were 4-fold: in multivariate analysis, neither intravenous iron administration in the whole population nor the weekly amount of iron in the subgroup of i.v. iron-treated patients were significant risk factors for bacteremia; iron was not given more frequently intravenously in bacteremic than in non-bacteremic patients; among patients treated with intravenous iron, the frequency and the amount of iron administered were significantly higher in those who developed bacteremia than in those who did not; and in patients receiving i.v. iron, there was an increased risk of bacteremia associated with concurrent administration of erythropoietin, which was not observed in patients receiving iron orally. CONCLUSION: This study failed to demonstrate a significant association between intravenous iron administration and the risk of bacteremia in dialysis patients. However, there might be a slightly increased risk of bacteremia in patients given high-frequency, high-dose intravenous iron.

[Effect of spasticity on functional capacity in spinal cord injuries: value of visual analogue scale (preliminary study)]. / Effet de la spasticité sur les capacités fonctionnelles des patients atteints de lésion médullaire : intérêt de l'évaluation par échelle visuelle analogique (étude préliminaire).

OBJECTIVES: Assessment of the influence of spasticity on activities of daily living in spinal cord injuries. MATERIAL AND METHODS: Fifteen patients with spinal cord injuries have been submitted to a clinical examination and functional assessment by FIM. They answer to a questionnaire on the influence of spasticity on 11 activities of daily living (response by visual analogic scale). RESULTS: The impact of spasticity in daily life is weak (evaluation of difficulties less than 3 on 10 for 7 of the 11 activities of daily living), except for transfers and precision motions when it is on superior limbs. Spasticity has never been considered as useful by patients (VAS less than 3 for 13 persons). DISCUSSION: This study discusses about the real functional influence of spasticity in daily life. It shows the insufficiency of currently used scales and their lack of sensibility to detect the effects of spasticity in daily life's activities. CONCLUSION: Further outcome studies are required to assess the functional role of spasticity in neurologic patients and the real interest of treatments.

[Characteristics of a cohort of 4,000 French patients with angina. The ELAN study]. / Caractéristiques d'une cohorte française de 4,000 patients angineux. L'étude ELAN.

The ELAN (Etude Longitudinale dans l'ANgor) study was carried out to evaluate factors influencing the occurrence of death, myocardial infarction and revascularization procedures in patients with known angina pectoris. Analysis of baseline data collected in January 1997 involves 4,035 patients throughout France, which were recruited by 613 cardiologists practising on a private, hospital or mixed basis. The study population comprised 75% of men with a mean age of 65 years and 25% of women with a mean age of 70 years. Eighty eight percent of the patients had at least one cardiovascular risk factor, and nearly half of them had two or more factors; hypercholesterolemia and hypertension were the two most frequent ones. Reported cardiovascular past events included myocardial infarction in 47% of patients, PTCA in 33% and aorto-coronary bypass in 24%. Angina pectoris had been diagnosed within the previous year in 39% of patients. Exertional angina was the most common type (66%), with grade I/II angina being most frequently found (more than 70% of all cases). Management strategies are especially described for angina patients diagnosed within the previous year. More than half of the patients had undergone exercise testing within the previous 12 months, while scanning and coronary arteriography had been performed in 15% and 72%, respectively. Ninety five percent of patients were under antianginal drug therapy, with combined therapies being used in 58% of them. The most frequently prescribed drugs were betablockers (63%) and nitrates (53%). In 74% of patients, aspirin was given in addition to conventional antianginal agents. These data will be reviewed in a one-year cohort analysis as potential predictive factors for the occurrence of cardiovascular events.