Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

Investigation into Red Emission and Its Applications: Solvatochromic N-Doped Red Emissive Carbon Dots with Solvent Polarity Sensing and Solid-State Fluorescent Nanocomposite Thin Films.

In this work, a NIR emitting dye, p-toluenesulfonate (IR-813) was explored as a model precursor to develop red emissive carbon dots (813-CD) with solvatochromic behavior with a red-shift observed with increasing solvent polarity. The 813-CDs produced had emission peaks at 610 and 698 nm, respectively, in water with blue shifts of emission as solvent polarity decreased. Subsequently, 813-CD was synthesized with increasing nitrogen content with polyethyleneimine (PEI) to elucidate the change in band gap energy. With increased nitrogen content, the CDs produced emissions as far as 776 nm. Additionally, a CD nanocomposite polyvinylpyrrolidone (PVP) film was synthesized to assess the phenomenon of solid-state fluorescence. Furthermore, the CDs were found to have electrochemical properties to be used as an additive doping agent for PVP film coatings.

Novel CAPN3 variant associated with an autosomal dominant calpainopathy.

AIMS: The most common autosomal recessive limb girdle muscular dystrophy is associated with the CAPN3 gene. The exclusively recessive inheritance of this disorder has been recently challenged by the description of the recurrent variants, c.643_663del21 [p.(Ser215_Gly221del)] and c.598_612del15 [p.(Phe200_Leu204del)], associated with autosomal dominant inheritance. Our objective was to confirm the existence of autosomal dominant calpainopathies. METHODS: Through our activity as one of the reference centres for genetic diagnosis of calpainopathies in France and the resulting collaborations through the French National Network for Rare Neuromuscular Diseases (FILNEMUS), we identified four families harbouring the same CAPN3 heterozygous variant with supposedly autosomal dominant inheritance. RESULTS: We identified a novel dominantly inherited CAPN3 variant, c.1333G>A [p.(Gly445Arg)] in 14 affected patients from four unrelated families. The complementary phenotypic, functional and genetic findings correlate with an autosomal dominant inheritance in these families, emphasizing the existence of this novel transmission mode for calpainopathies. The mild phenotype associated with these autosomal dominant cases widens the phenotypic spectrum of calpainopathies and should therefore be considered in clinical practice. CONCLUSIONS: We confirm the existence of autosomal dominant calpainopathies as an entity beyond the cases related to the in-frame deletions c.643_663del21 and c.598_612del15, with the identification of a novel dominantly inherited and well-documented CAPN3 missense variant, c.1333G>A [p.(Gly445Arg)]. In addition to the consequences for genetic counselling, the confirmation of an autosomal dominant transmission mode for calpainopathies underlines the importance of re-assessing other myopathies for which the inheritance is considered as strictly autosomal recessive.

Popliteal Artery Entrapment Syndrome in Children: Experience With Four Cases of Acute Ischaemia and Review of the Literature.

OBJECTIVE: Popliteal artery entrapment syndrome (PAES) is an uncommon anatomical anomaly, frequently described in adults. The most common symptom is claudication. Acute limb ischaemia (ALI) in children is rare, but it may evolve and lead to limb loss or lifelong complications. Clinical and surgical experience of PAES in children is reported. Data from the literature are analysed in order to assess the severity of this disease and to identify the factors characterising the diagnosis and the outcome of treatment in paediatric patients. METHODS: Four children (aged 7-16 years) were referred with ALI due to PAES. Among the 439 articles reporting cases of PAES, 55 patients under 18 years of age were the focus. The PAES cases were classified according to the Love and Whelan classification modified by Rich. RESULTS: Data from 79 children (106 limbs, 27 bilateral PAES) were collected and analysed. Type I PAES was present in 41 (39%), Type II in 23 (22%), Type III in 24 (23%), Type IV in 12 (11%), and Type V in two (2%) limbs. A functional PAES was present in one patient bilaterally. In two cases, the type of PAES was not reported. Claudication occurred in 68 cases (64%), and ALI in 19 (18%). In 60 cases (57%), revascularisation with or without myotomy was required; myotomy alone was performed in 41 cases (39%). CONCLUSIONS: Symptomatic PAES in children should be considered a severe condition requiring urgent investigation in order to avoid any delays in the treatment. Early diagnosis and treatment are essential to prevent serious complications. The long-term outcomes of surgical treatment with the correction of the anatomical anomaly and vascular reconstruction are satisfactory with a low complication rate.

Amplatzer Plug to Occlude the Internal Iliac Artery During Endovascular Aortic Aneurysm Repair: A Large Multicenter Study.

OBJECTIVE: During endovascular repair of abdominal aortic aneurysms (EVAR), in the absence of a distal iliac landing zone, the Amplatzer plug is increasingly being used to replace other internal iliac artery (IIA) embolization techniques. This study aimed at assessing the technical success, complication occurrence, and durability of the Amplatzer plug for IIA embolization. METHOD: From January 1, 2007 to December 31, 2013, all consecutive patients who underwent internal iliac embolization with an Amplatzer plug during EVAR were included in the study. There were 169 patients, (160 men, 9 women, mean 75 ± 9 years), treated by unilateral (158 cases, 93%) or bilateral (11 cases, 7%) embolization of the IIA, performed either separately prior to (65 cases, 38.5%) or during EVAR (104 cases, 61.5%). Follow up CT scan and/or US scan were performed 1 month after treatment and yearly thereafter. The inclusions were done retrospectively but the series was continuous and consecutive. Data were collected and analyzed using acquisition REDCap software. RESULTS: The technical success rate was 97.6%. Failures were device migration (n = 1), navigation failure (n = 2), and release outside the target zone (n = 1). On average, 1.43 plugs were required to achieve the embolization. The average amount of contrast agent for the embolization procedure was 111 ± 51 mL and the radiation dose was 127,777 ± 89,528 mGy/cm(2). The total fluoroscopy time was 854 ± 538 seconds. No re-canalization of the IIA trunk was observed during follow up. Complications were buttock claudication (n = 41, 24.3%), which resolved in 24 cases (58.5%, 24/41) at the first follow up, and intestinal ischemia requiring limited bowel resection in two cases. CONCLUSION: This multicenter study is the largest published to date. It demonstrates the efficacy and reliability of the Amplatzer plug to embolize the IIA during EVAR, with few side effects.

Clinical massively parallel sequencing for the diagnosis of myopathies.

Massively parallel sequencing, otherwise known as high-throughput or next-generation sequencing, is rapidly gaining wide use in clinical practice due to possibility of simultaneous exploration of multiple genomic regions. More than 300 genes have been implicated in neuromuscular disorders, meaning that many genes need to be considered in a differential diagnosis for a patient affected with myopathy. By providing sequencing information for numerous genes at the same time, massively parallel sequencing greatly accelerates the diagnostic processes of myopathies compared to the classical "gene-after-gene" approach by Sanger sequencing. In this review, we describe multiple advantages of this powerful sequencing method for applications in myopathy diagnosis. We also outline recent studies that used this approach to discover new myopathy-causing genes and to diagnose cohorts of patients with muscular disorders. Finally, we highlight the key aspects and limitations of massively parallel sequencing that a neurologist considering this test needs to know in order to interpret the results of the test and to deal with other issues concerning the test.

Are sputum eosinophil cationic protein and eosinophils differently associated with clinical and functional findings of asthma?

BACKGROUND: Sputum eosinophil counts and eosinophil cationic protein (ECP) levels are usually increased in asthmatic patients. The correlation between sputum eosinophils or ECP and clinical findings of asthma has been previously investigated but many of these studies have been performed on small samples of asthmatic patients, considering only few clinical indices and often including patients on oral or inhaled corticosteroids, which might be confounding when interpreting the relationship between disease activity and airway inflammation. OBJECTIVE: To assess whether sputum eosinophils and ECP were differently related to functional and clinical parameters of asthma in a large number of steroid-naïve asthmatic patients, taking into account several potential determinants of activity and chronicity of asthma. METHODS: One hundred and twenty-nine patients with mild-moderate asthma were studied. Sputum was induced by hypertonic saline inhalation and processed using the whole sample method. RESULTS: Sputum eosinophils and ECP significantly correlated with each other (r = 0.41, P < 0.001). When patients were grouped on the basis of high/low sputum eosinophils and high/low sputum ECP levels, significant differences were observed among groups, with patients with high sputum eosinophils and ECP showing the greatest asthma severity. In the overall sample, disease duration inversely correlated with sputum eosinophils, whereas FEV1 and peak expiratory flow (PEF) inversely correlated with sputum ECP. Rescue ß2 -agonist use and total symptom score positively correlated with both eosinophil counts and sputum ECP. Stepwise regression analysis showed that symptom score and disease duration accounted for 17.6% of sputum eosinophil variance, whereas symptom score and FEV1 accounted for 14.7% of sputum ECP variance. CONCLUSIONS AND CLINICAL RELEVANCE: Both sputum eosinophils and ECP are weakly related to clinical markers of asthma severity. However, ECP was more closely related to lung function parameters than eosinophil counts.

The art of simplicity: Water-soluble porphyrin-like carbon dots self-assemble into mesmerizing red glow.

In this new study, we present an intriguing development in the field of theranostics: the simplistic self-assembly of red-emissive amphiphilic porphyrin-like carbon dots (P-CDs). By harnessing their exceptional photophysical properties, we have revealed a strong candidate as the ideal photosensitizer (PS) for applications, particularly in the realm of imaging. Spanning a remarkable size average between 1-4 nm, these particles exhibit both highly stable and unparalleled emission characteristics between 650 and 715 nm in water in comparison to current carbon dots (CDs) available. Lastly, these CDs were fairly non-toxic when tested against normal human cell lines as well as were found to have favorable imaging capabilities in zebrafish embryo.

Advancing glioblastoma imaging: Exploring the potential of organic fluorophore-based red emissive carbon dots.

Over time, the interest in developing stable photosensitizers (PS) which both absorb and emit light in the red region (650 and 950 nm) has gained noticeable interest. Recently, carbon dots (CDs) have become the material of focus to act as a PS due to their high extinction coefficient, low cytotoxicity, and both high photo and thermal stability. In this work, a Federal and Drug Association (FDA) approved Near Infra-Red (NIR) organic fluorophore used for photo-imaging, indocyanine green (ICG), has been explored as a precursor to develop water-soluble red emissive CDs which possess red emission at 697 nm. Furthermore, our material was found to yield favorable red-imaging capabilities of glioblastoma stem-like cells (GSCs) meanwhile boasting low toxicity. Additionally with post modifications, our CDs have been found to have selectivity towards tumors over healthy tissue as well as crossing the blood-brain barrier (BBB) in zebrafish models.

May the reduction of exposure to specific sensitizers be an alternative to work cessation in occupational asthma? Results from a follow-up study.

BACKGROUND: Few data are reported on the effects of a reduction of exposure to specific sensitizers in occupational asthma (OA). The objective of this study was to evaluate the clinical outcome of subjects with OA, comparing the effect of a reduction with that of the persistence or cessation of occupational exposure to the specific sensitizer. SUBJECTS AND METHODS: Forty-one subjects with OA due to different sensitizers were diagnosed via a specific inhalation challenge. After a follow-up interval of 3.5 years, subjects were reexamined by clinical assessment, bronchial hyperresponsiveness (BH) and induced sputum. RESULTS: At follow-up, subjects who had reduced occupational exposure (n = 22) showed a significant improvement in BH and a nonsignificant improvement in sputum eosinophilia (from 5.3 to 1.1%, n.s.), while subjects still exposed (n = 10) showed a significant decrease in FEV(1). Subjects who ceased work (n = 9) showed a trend of improvement in BH and sputum eosinophilia. Logistic analysis showed that the major determinant of improvement in BH at follow-up was the severity of BH at diagnosis, with a minimal contribution from the duration of exposure and treatment with inhaled corticosteroids during follow-up; reduction of work exposure did not enter into any model. CONCLUSION: The reduction of occupational exposure could not be considered to be as effective as work cessation, which remained the best treatment for OA. However, it was not associated with a deterioration of FEV(1) as observed in subjects with persistent exposure.

In vivo assessment of murine elastase-induced abdominal aortic aneurysm with high resolution magnetic resonance imaging.

OBJECTIVES: There are, to date, no published non-invasive or longitudinal studies performed in mice to measure aortic diameter and wall thickness in an elastase-induced abdominal aortic aneurysm. This MRI study at 11.75 T aimed at evaluating the reliability of longitudinal in vivo aortic diameter and wall thickness measurements in this particular model. METHODS: Adult male C57BL/6 mice underwent transient elastase or heat-inactivated elastase perfusion (controls). Aortic dilatation was measured before, during and immediately after elastase perfusion, and again 14 days after, with a calibrated ocular grid. MRI was performed just before initial surgery and at day 14 before harvest using an 11.75 T MR microscopy imager. RESULTS: Aortic diameter was significantly greater in elastase-perfused mice compared to controls as measured by optic grid (1.150 ± 0.153 mm vs 0.939 ± 0.07 mm, P = 0.038) and according to MRI measurement of the outer diameter on spin echo images (1.203 ± 0.105 mm vs 1070 ± 0.048 mm, P = 0.0067). Aortic wall thickness was found to be significantly increased in elastase-perfused mice at day 14. CONCLUSIONS: This study demonstrates in the mouse elastase-induced aneurysm model that characterization of aneurysm development by its inner and outer vessel diameter and vessel wall thickness can be carried out longitudinally using high resolution MRI without significant mortality.

Circulating lipoprotein-associated phospholipase A2 in high-grade carotid stenosis: a new biomarker for predicting unstable plaque.

OBJECTIVE: To test plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with high-grade carotid stenosis according to plaque histology. METHODS: This cross-sectional single-centre study included patients with ≥70% North American Symptomatic Carotid Endarterectomy Trial (NASCET) carotid stenosis, who were treated surgically. Serum Lp-PLA2 and high-sensitivity C-reactive protein (hs-CRP) were determined on the day of surgery. Histopathological analysis classified carotid plaque as stable or unstable, according to AHA classification. RESULTS: Of the 42 patients (mean age 70.4 ± 10.5 years; 67% men), neurological symptoms were present in 16 (38%). Unstable plaques were found in 23 (55%). Median plasma level of Lp-PLA2 was significantly higher in patients with unstable plaque compared to those with stable plaque (222.4 (174.9-437.5) interquartile range (IQR) 63.5 vs. 211.1 (174.9-270.6) IQR 37.2 ng ml(-1); p = 0.02). Moreover, median Lp-PLA2 level were higher in asymptomatic patients with unstable plaque (226.8 ng ml(-1) (174.9-437.5) IQR 76.8) vs. stable plaque (206.9 ng ml(-1) (174.9-270.6) IQR 33.7; p = 0.16). Logistic regression showed that only the neurological symptoms (OR = 30.9 (3.7-244.6); p < 0.001) and the plasma Lp-PLA2 level (OR = 1.7 (1.1-12.3); p = 0.03) were independently associated with unstable carotid plaque as defined by histology. CONCLUSIONS: This study showed that circulating Lp-PLA2 was increased in patients with high-grade carotid stenosis and unstable plaque. Lp-PLA2 may be a relevant biomarker to guide for invasive therapy in asymptomatic patients with carotid artery disease.

Endovascular approaches to acute aortic type A dissection: a CT-based feasibility study.

BACKGROUND: Open graft replacement of the ascending aorta is the current treatment of choice for Stanford acute type A dissections. However, approximately 20% of patients are deemed unfit for open surgery. To determine if an endovascular option exists for this latter group of patients, we performed a computed tomography (CT)-based feasibility study. METHODS: A cohort of consecutive patients presenting to the cardiovascular care unit (CVCU) for an acute Stanford type A aortic dissection between 2006 and 2009 was retrospectively analysed. Inclusion criterion was a high-quality preoperative angio-CT scan that could be analysed on a three-dimensional (3D) workstation. Numerous anatomical parameters of the dissection were studied, including the location and the length of the primary proximal entry tear. Finally, we determined which of the patients would have been potential candidates for an endovascular repair (stentgraft implantation). RESULTS: A total of 102 patients were included in our study. The median distance of the primary entry tear to the closest coronary artery was 23 mm (range 0-128). The median true lumen and true + false lumen (total) diameters at the level of the entry tear was 38 mm (range 22-78) and 46 mm (range 28-93), respectively. The median length of the ascending aorta was 84 mm (range 40-130). An endovascular repair with a tubular stentgraft was deemed feasible in 37 patients. An additional eight patients were also candidates for a tubular endovascular repair but would have required a carotidecarotid cross over bypass. Finally, an arch-branched stentgraft could have been used in 13 patients to exclude an entry tear located in the arch. CONCLUSION: Open repair of acute type A dissection is and remains the 'gold standard' of care. Our study demonstrates that approximately half the patients undergoing an open repair could potentially benefit from an endovascular repair. This new treatment option has not been evaluated to date.

Malondialdehyde in exhaled breath condensate as a marker of oxidative stress in different pulmonary diseases.

BACKGROUND: Oxidative stress plays a role in the pathogenesis of many chronic inflammatory lung diseases. Exhaled breath condensate (EBC) collection is a noninvasive method to investigate pulmonary oxidative stress biomarkers such as malondialdehyde (MDA). SUBJECTS AND METHODS: We measured MDA levels in EBC in a large number of patients (N = 194) with respiratory diseases: asthma (N = 64), bronchiectasis (BE, N = 19), chronic obstructive pulmonary disease (COPD, N = 73), idiopathic pulmonary fibrosis (IPF, N = 38). Fourteen healthy nonsmoking subjects were included as controls. RESULTS: Excluding IPF subjects, MDA levels were significantly higher in all disease groups than in control group. MDA was significantly higher in COPD than asthmatic and BE subjects. Among asthmatics, corticosteroids-treated subjects had lower MDA levels than untreated subjects. COPD subjects showed an inverse correlation between MDA concentrations and FEV(1)% (rho: -0.24, P < .05). CONCLUSIONS: EBC-MDA is increased in subjects with chronic airway disorders, particularly in COPD, and it is related to FEV(1) reduction.

Ultrasound arterial anomalies in patients exposed to nilotinib therapy for chronic myeloid leukemia.

INTRODUCTION: Patients exposed to nilotinib for chronic myeloid leukemia (CML) appear to be at risk of arterial complication. The prevalence and aspect of ultrasound asymptomatic arterial lesions are unknown. OBJECTIVE: To describe prevalence and characteristics of ultrasound arterial anomalies in patients treated with nilotinib for CML. METHODS: Patients treated with nilotinib from 2006 to 2015 in the department of the Paoli-Calmettes Institute, Marseille, were included retrospectively. A vascular ultrasound screening was carried out from 2010. The arterial lesions at the first examination were described: plaque and its echogenicity, stenosis or occlusion. A vascular arterial anomaly (VAA) was defined by the presence of a clinical and/or ultrasound anomaly. Patients with or without VAA at initial vascular examination were compared using bivariate and multivariate analysis. RESULTS: 74 patients were included (51.4% men, mean age 54.5 years); 25 patients had ultrasound arterial anomalies (33.8%). Carotid bulb was the most involved territory (44%). Arterial anomalies were: 88% plaques, 44%>50% stenosis and 12% occlusion. 72.7% plaques were echolucent or hypoechogenic. A VAA was present in 25 patients with initial vascular evaluation (33.8%). Patients with VAA at baseline were significantly older (64.9 vs 49.3, P<0.001), older at nilotinib initiation (60.8 vs 46.5, P<0.001), with more arterial hypertension (40% vs 12.2%, P=0.01), with more cardiovascular risk factors (P=0.03). In patient with no cardiovascular risk factor 12.5% had VAA (n=24). CONCLUSION: Nilotinib seems to be associated to arterial lesions of unstable lipid-like appearance. The most involved arterial territory was the carotid bulb and the most common lesion was echolucent or hypoechogenic plaque. VAA can occur in patients without cardiovascular risk factors. This result encourages us to systematically screen and follow all patients exposed to nilotinib even those without cardiovascular risk factors.

In situ revascularization with rifampicin-soaked silver polyester graft for aortic infection: Results of a retrospective monocentric series of 18 cases.

OBJECTIVE: To evaluate the short and long-term results of in situ prosthetic graft treatment using rifampicin-soaked silver polyester graft in patients with aortic infection. MATERIAL AND METHOD: All the patients surgically managed in our center for an aortic infection were retrospectively analyzed. The primary endpoint was the intra-hospital mortality, secondary outcomes were limb salvage, persistent or recurrent infection, prosthetic graft patency, and long-term survival. RESULTS: From January 2004 to December 2015, 18 consecutive patients (12 men and 6 women) were operated on for aortic infection. Six mycotic aneurysms and 12 prosthetic infections, including 8 para-entero-prosthetic fistulas, were treated. In 5 cases, surgery was performed in emergency. During the early postoperative period, we performed one major amputation and two aortic infections were persistent. Intra-hospital mortality was 27.7%. The median follow-up among the 13 surviving patients was 26 months. During follow-up, none of the 13 patients presented reinfection or bypass thrombosis. CONCLUSION: This series shows that in situ revascularization with rifampicin-soaked silver polyester graft for aortic infection have results in agreement with the literature in terms of intra-hospital mortality with a low reinfection rate.

Vascular endothelial growth factor in eye disease.

Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the US, for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

A novel calmodulin-binding protein, belonging to the WD-repeat family, is localized in dendrites of a subset of CNS neurons.

A rat brain synaptosomal protein of 110,000 M(r) present in a fraction highly enriched in adenylyl cyclase activity was microsequenced (Castets, F., G. Baillat, S. Mirzoeva, K. Mabrouk, J. Garin, J. d'Alayer, and A. Monneron. 1994. Biochemistry. 33:5063-5069). Peptide sequences were used to clone a cDNA encoding a novel, 780-amino acid protein named striatin. Striatin is a member of the WD-repeat family (Neer, E.J., C.J. Schmidt, R. Nambudripad, and T.F. Smith. 1994. Nature (Lond.). 371:297-300), the first one known to bind calmodulin (CaM) in the presence of Ca++. Subcellular fractionation shows that striatin is a membrane-associated, Lubrol-soluble protein. As analyzed by Northern blots, in situ hybridization, and immunocytochemistry, striatin is localized in the central nervous system, where it is confined to a subset of neurons, many of which are associated with the motor system. In particular, striatin is conspicuous in the dorsal part of the striatum, as well as in motoneurons. Furthermore, striatin is essentially found in dendrites, but not in axons, and is most abundant in dendritic spines. We propose that striatin interacts, through its WD-repeat domain and in a CaM/Ca(++)-dependent manner, with one or several members of a surrounding cluster of molecules engaged in a Ca(++)-signaling pathway specific to excitatory synapses.

The haemodynamics of the distal arterial Y-shaped autograft bypass-flap in a porcine experimental model.

BACKGROUND: The haemodynamic effects of revascularisation with combined bypass and free-muscle flap remain controversial. In a porcine experimental model, we investigated the transplantation-induced changes in the haemodynamics of a Y-shaped combined arterial autograft bypass-muscle flap (AABF). METHODS: Anatomy of AABF was identified in eight dissections in four porcine cadavers. In five animals, AABF served as a superficial femoral artery (SFA) defect replacement. Modelled, triggered pulsatile pressure (P) and flow (Q) waves delivered mean haemodynamics and PQ hysteresis loops before and after transplantation at days 0 and 10. RESULTS: Anatomically, AABF combined subscapular and circumflex-scapular arteries, and thoracodorsal artery as latissimus dorsi flap pedicle. Surgical feasibility and AABF patency were confirmed in each case. At day 0, the proximal flow was increased in the grafted Y-shaped AABF, which also adopted the specific SFA pulsatile haemodynamics. Regulatory mechanisms of AABF vasomotricity were preserved and AABF-flow-dependence amplified the flow in the distal segment, which otherwise preserved its own flow dependence. At 10 days, the AABF flow was unchanged in the distal segment, and remained elevated in the proximal and pedicle segments. CONCLUSIONS: Combined AABF, as a single one-piece arterial autograft, was shown highly adaptive to the receiving arteries. The transplantation-induced changes in AABF pulsatile flow profile and vascular reactivity improve the overall graft flow, and strongly advocate for beneficial effects on the blood propelling capacity of the grafted circulation.

Early carotid endarterectomy after intravenous thrombolysis for acute ischaemic stroke.

UNLABELLED: After intravenous thrombolysis (IVT) for acute ischaemic stroke (AIS), a severe cervical internal carotid artery (ICA) stenosis may remain and increase the risk of recurrent stroke. Carotid endarterectomy (CEA) has been shown to be effective in reducing the risk of stroke. However, it is not well known whether CEA can be performed safely after thrombolysis, and, if so, when. We report a prospective study of CEA for residual high-grade cervical ICA stenosis performed within 15 days after IVT for AIS. METHODS: All the patients had a brain magnetic resonance imaging (MRI) within 3h of the stroke onset. One day after IVT in neurovascular unit, computed tomography (CT) angiography was performed to assess the brain and the patency of cervical arteries. CEA was performed on neurologically stable patients after full cerebral artery re-canalisation. Blood pressure was controlled with particular caution before and after CEA. RESULTS: Between January 2005 and January 2008, we operated consecutively on 12 patients. Their median National Institutes of Health Stroke Scale (NIHSS) score was 12 (range: 5-21). Combined intracranial (ICA)-middle cerebral artery (MCA) occlusion was present in 58.3% of the patients. The median time between onset of symptoms until CEA was 8 days (range: 1-16 days). Stroke and death rate at 30 days was 8.3% (one nonfatal haemorrhagic stroke). At 90 days, nine patients had a Rankin score of 0-1, one had a score of 2 and two had a score of 3. CONCLUSION: In patients with residual cervical ICA stenosis after IVT, we achieved full patency of the occluded artery and good functional prognosis at 3 months in all cases. We advocate for an extremely close monitoring of the blood pressure in the pre-, peri- and post-operative course and a close collaboration between neurologist and surgeon to determine the best timing for CEA.