Phenotypic spectrum of Charcot-Marie-Tooth disease due to LITAF/SIMPLE mutations: a study of 18 patients.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth (CMT) 1C due to mutations in LITAF/SIMPLE is a rare subtype amongst the autosomal dominant demyelinating forms of CMT. Our objective was to report the clinical and electrophysiological characteristics of 18 CMT1C patients and compare them to 20 patients with PMP22 mutations: 10 CMT1A patients and 10 patients with hereditary neuropathy with liability to pressure palsies (HNPP). METHODS: Charcot-Marie-Tooth 1C patients were followed-up in referral centres for neuromuscular diseases or were identified by familial survey. All CMT1A and HNPP patients were recruited at the referral centre for neuromuscular diseases of Pitié-Salpêtrière Hospital. RESULTS: Two phenotypes were identified amongst 18 CMT1C patients: the classical CMT form ('CMT-like', 11 cases) and a predominantly sensory form ('sensory form', seven cases). The mean CMT neuropathy score was 4.45 in CMT1C patients. Motor nerve conduction velocities in the upper limbs were significantly more reduced in CMT1A than in CMT1C patients. On the other hand, the motor nerve conduction velocity of the median nerve was significantly lower in CMT1C compared to the HNPP group. Distal motor latency was significantly more prolonged in CMT1A patients compared to the CMT1C and HNPP groups, the latter two groups having similar distal motor latency values. Molecular analysis revealed five new LITAF/SIMPLE mutations (Ala111Thr, Gly112Ala, Trp116Arg, Pro135Leu, Arg160Cys). CONCLUSIONS: Our study delineates CMT1C as mostly a mild form of neuropathy, and gives clinical and electrophysiological clues differentiating CMT1C from CMT1A and HNPP. Delineating phenotypes in CMT subtypes is important to orient molecular diagnosis and to help to interpret complex molecular findings.

Impact of perioperative immunosuppressive medication on surgical outcome in Crohn's Disease (CD).

INTRODUCTION: Patients with Crohn's disease [CD] carry an 80 - 90 % lifetime risk of undergoing surgery. Many of these patients are on immunosuppressive medication at the time of surgery. The aim of this study was to evaluate the effect of immunosuppression on the surgical outcome in CD patients. METHODS: We retrospectively analyzed 484 consecutive abdominal operations for CD from 1995 to 2008 for surgical complications. RESULTS: A total of 241 operations (= 49.8 %) were performed under perioperative immunosuppression (corticoids and thiopurine). The overall complication rate was 18.6 %, the major complication rate was 8.7 % and the anastomotic leakage rate was 3.3 %. No differences were observed between patients without immunosuppression compared to those with immunosuppression. Patients with colo-rectal resections showed a higher complication rate than patients with small bowel resection independently of immunosuppression. CONCLUSION: Nearly 50 % of the patients undergoing abdominal surgery for CD are receiving immunosuppressive medication during surgery. However, perioperative immunosuppression with corticoids, thiopurine or the combination of both does not significantly alter the surgical complication rate. Therefore the decision of a required surgery should not be delayed due to the fact that the patient is under immunosuppressive medication.

Combined anatomical and functional imaging using coronary CT angiography and myocardial perfusion SPECT in symptomatic adults with abnormal origin of a coronary artery.

There has been a lack of standardized workup guidelines for patients with congenital abnormal origin of a coronary artery from the opposite sinus (ACAOS). We aimed to evaluate the use of cardiac hybrid imaging using multi-detector row CT (MDCT) for coronary CT angiography (Coronary CTA) and stress-rest myocardial perfusion SPECT (MPS) for comprehensive diagnosis of symptomatic adult patients with ACAOS. Seventeen symptomatic patients (12 men; 54 ± 13 years) presenting with ACAOS underwent coronary CTA and MPS. Imaging data were analyzed by conventional means, and with additional use of 3D image fusion to allocate stress induced perfusion defects (PD) to their supplying coronary arteries. An anomalous RCA arose from the left anterior sinus in eight patients, an abnormal origin from the right sinus was detected in nine patients (5 left coronary arteries, LCA and 4 LCx). Five of the 17 patients (29%) demonstrated a reversible PD in MPS. There was no correlation between the anatomical variants of ACAOS and the presence of myocardial ischemia. Image fusion enabled the allocation of reversible PD to the anomalous vessel in three patients (two cases in the RCA and the other in the LCA territory); PD in two patients were allocated to the territory of artery giving rise to the anomalies, rather than the anomalies themselves. In a small cohort of adult symptomatic patients with ACAOS anomaly there was no relation found between the specific anatomical variant and the appearance of stress induced myocardial ischemia using cardiac hybrid imaging.

[Telemedicine and fibrinolysis in Franche-Comté]. / Télémédecine et fibrinolyse de l'ischémie cérébrale en Franche-Comté

INTRODUCTION: The aim of our study was to compare the efficacy and safety of intravenous thrombolysis of cerebral ischemia as it has been established in a distant hospital (DH) through telemedicine tools or in neurovascular unit of the University Hospital of Besançon. METHOD: Our work was conducted retrospectively at the University Hospital of Besançon from 1 January 2003 to December 31, 2009. RESULTS: Fibrinolysis was introduced at the university hospital in 98/161 patients (61%) and a DH in remote 63/161 patients (39%). A favorable neurological outcome (Rankin 0/1) was observed in 27/98 patients (27.5%) treated at University Hospital and in 25/63 (39.5%) patients in a DH. There was no significant difference between the two subgroups. Symptomatic hemorrhagic transformation occurred in 5/98 (5%) patients treated at University Hospital and in 1/63 (1.5%) patients treated in DH. There was no significant difference between the two subgroups. CONCLUSION: Our study shows that fibrinolysis remotely using the tools of telemedicine has, from 2003 to 2009, in Franche-Comté deal effectively and without risk of a significant proportion of patients.

Cardiac involvement is frequent in patients with the m.8344A>G mutation of mitochondrial DNA.

BACKGROUND: Cardiac complications, such as myocardial disease and arrhythmias, are frequent and may be severe in patients with mitochondrial disease. We sought to determine the prevalence and the prognostic value of cardiac abnormalities in a series of patients carrying the m.8344 A>G mutation. METHODS: We retrospectively collected data concerning a cohort of patients carrying the m.8344A>G mutation. Patients systematically underwent neurologic examination, muscular biopsy, measurement of forced vital capacity, and cardiac evaluation including electrocardiogram, echocardiography, and 24-hour ambulatory electrocardiogram at diagnosis. Neurologic and cardiac evaluations were repeated during follow-up at least every 2 years. RESULTS: Eighteen patients (mean age 39.3 +/- 17.3 years, 10 women) from 8 families were investigated. Mean follow-up duration was 5.0 +/- 2.7 years. Cardiac abnormalities were identified at diagnosis in 8 patients (44.4%, age 39.1 +/- 17.7 years), including dilated cardiomyopathy in 4, Wolff-Parkinson-White syndrome in 3, incomplete left bundle branch block in 1, and ventricular premature beats in 1. Two additional patients developed left ventricular dysfunction during follow-up and 2 patients died due to heart failure. Subgroup analyses identified early age at disease onset as the only factor significantly associated with myocardial dysfunction. CONCLUSIONS: We identified a high prevalence of ventricular dysfunction and Wolff-Parkinson-White syndrome. Myocardial involvement was associated with an increased risk of cardiac death due to heart failure, suggesting that cardiac investigations should be systematically considered in patients carrying the m.8344A>G mutation.

First observation of a tetra-anionic metal cluster, Al(n)(4-).

The production of aluminum cluster tetra-anions, and thus the first observation of a tetra-anionic metal cluster in the gas-phase, is reported. The aluminum cluster polyanions were generated by use of the "electron-bath technique." The smallest tetra-anion observed was Al(215) (4-), containing 14% fewer atoms than expected from classical estimates of the tetra-anion appearance size.

Combined use of 64-slice computed tomography angiography and gated myocardial perfusion SPECT for the detection of functionally relevant coronary artery stenoses. First results in a clinical setting concerning patients with stable angina.

AIM: In patients with stable angina pectoris both morphological and functional information about the coronary artery tree should be present before revascularization therapy is performed. High accuracy was shown for spiral computed tomography (MDCT) angiography acquired with a 64-slice CT scanner compared to invasive coronary angiography (ICA) in detecting "obstructive" coronary artery disease (CAD). Gated myocardial SPECT (MPI) is an established method for the noninvasive assessment of functional significance of coronary stenoses. Aim of the study was to evaluate the combination of 64-slice CT angiography plus MPI in comparison to ICA plus MPI in the detection of hemodynamically relevant coronary artery stenoses in a clinical setting. PATIENTS, METHODS: 30 patients (63 +/- 10.8 years, 23 men) with stable angina (21 with suspected, 9 with known CAD) were investigated. MPI, 64-slice CT angiography and ICA were performed, reversible and fixed perfusion defects were allocated to determining lesions separately for MDCT angiography and ICA. The combination of MDCT angiography plus MPI was compared to the results of ICA plus MPI. RESULTS: Sensitivity, specificity, negative and positive predictive value for the combination of MDCT angiography plus MPI was 85%, 97%, 98% and 79%, respectively, on a vessel-based and 93%, 87%, 93% and 88%, respectively, on a patient-based level. 19 coronary arteries with stenoses > or =50% in both ICA and MDCT angiography showed no ischemia in MPI. CONCLUSION: The combination of 64-slice CT angiography and gated myocardial SPECT enabled a comprehensive non-invasive view of the anatomical and functional status of the coronary artery tree.

[Detection and characterization of atherosclerotic coronary plaques with multislice spiral computed tomography]. / Kardiale Risikostratifizierung: Den atherosklerotischen Plaque im Blick.

Provided that adequate image quality is achieved, contrast-enhanced multislice spiral computed tomography enables the identification and characterisation of calcified and non-calcified coronary plaques. This is a major advance in the non-invasive assessment of coronary atherosclerosis that promises to open up new opportunities for a better understanding and risk stratification of this condition, with visualization of non-calcified hypodense lesions in particular appearing to be of prognostic importance. Current limitations of the technique relating mainly to temporal and spatial resolution may be eliminated by the introduction of a new generation of scanners enabling 64 slices and more.

Sorption mechanisms of zinc to calcium silicate hydrate: X-ray absorption fine structure (XAFS) investigation.

In this study, X-ray absorption fine structure (XAFS) spectroscopy has been used to further elucidate the binding mechanisms of Zn(II) to calcium silicate hydrate (C-S-H), the quantitatively most important cement mineral. Such knowledge is essential for the assessment of the longterm behavior of cement-stabilized waste materials. XAFS spectra of the Zn(II) equilibrated with C-S-H(I) for up to 28 days are best modeled by tetrahedral coordination of Zn(II) by four O atoms in the first atomic shell. Beyond the first coordination shell, data analysis of more highly concentrated samples suggests the presence of two distinct Zn distances and possibly the presence of an Si shell. On the basis of the comparison with a set of reference compounds, this coordination environment can be reasonably related to the structure of hemimorphite, a naturally occurring zinc silicate, and/or the presence of gamma-Zn(OH)2. At the lowest Zn uptake, the above fitting approach failed and data could be described best with a Zn-Si and a Zn-Ca shell. Previous work has been able to show that Zn(II) diffuses into the C-S-H(I) particles and does not form discrete precipitates, so the findings appear to confirm the incorporation of Zn(II) in the interlayer of C-S-H(I).

Should a single centre for the assay of biochemical markers of nutritional status be mandatory in multicentric trials?

Clinical trials to identify patients at risk and to assess new therapeutic agents in the nutritional field are often single-site. The principal advantage of mounting a multicentric trial is that patient accrual is much quicker. Albumin, transthyretin, and C-reactive protein are frequently used biochemical markers of nutritional and inflammation status. However, the different techniques, reagents, and calibrators used to measure these markers introduce wide variations in values among laboratories. This study was carried out as part of a prospective multicentric study in chronic respiratory disease patients to evaluate variability and comparability of results among laboratories for these biochemical markers, and to determine whether centralization is necessary. Thirty enrolled laboratories provided their own range of reference values for those proteins a nd were then requested to process two control samples C1 and C2 blind. The results showed a broad dispersion of values for albumin and transthyretin. In 7% of laboratories, results of albumin for C2 (mean, all techniques: 39.1+/-3 g/l) were <35 g/l, the threshold value indicating a potential risk of malnutrition. When only laboratories using immunonephelemetry were considered, the results were satisfactory (CV<10% for all proteins). Given the possible incorrect classification of patients at risk, measurement should be made per site only if all participants use an immunonephelometric method. Otherwise, a centralizing assay of these biological markers should be considered.

Sorption mechanisms of zinc to calcium silicate hydrate: sorption and microscopic investigations.

Knowledge of the binding mechanisms of heavy metals to cement minerals is essential for the prediction of the long-term leachability of secondary building materials and cement-stabilized wastes containing heavy metals. In this study, the sorption of Zn(II) to calcium silicate hydrate (C-S-H(I)) in pre-equilibrated aqueous suspensions has been investigated as a function of time (up to 87 d), pH (11.7, 12.48, and 12.78) and Zn(II) concentration (4.8-4800 microM). Electron probe microanalysis (EPMA) was performed in order to determine where Zn(II) was bound. At high Zn(II) concentrations (>1000 microM), the precipitation of beta2-Zn-(OH)2 (< pH 12) and calcium zincate (Zn2Ca(OH)6 x 2H2O, > pH 12) was observed. Surface precipitation could not be discerned. At lower concentrations, it was found that the sorption process was initially very rapid with over 50% sorbed within 30 min but that the sorption continued more slowly to at least 87 d. The data could be interpreted in terms of the Freundlich isotherm up to a Si:Zn(II)sorbed atomic ratio of approximately 6:1. Zinc was observed by EPMA to incorporate into the C-S-H(I) particles but did not appear to substitute for Ca or Si. The incorporation of Zn(ll) in the interlayer of C-S-H(I) or sorption to internal surfaces of crystalline appear to be the most probable mechanisms for the observed Zn(II) sorption to C-S-H(I).

Formation of 9,10-unsaturation in the mitomycins: facile fragmentation of beta-alkyl-beta-aryl-alpha-oxo-gamma-butyrolactones.

A facile fragmentation of beta-alkyl-beta-aryl-alpha-oxo-gamma-butyrolactones is reported. A study to assist in the elucidation of the mechanism of the reaction is also revealed.

[Cavernous sinus lymphoma mimicking Tolosa-Hunt syndrome]. / Lymphome du sinus caverneux mimant un syndrome de Tolosa-Hunt.

INTRODUCTION: Tolosa-Hunt syndrome is characterized by painful ophthalmoplegia due to idiopathic granulomatous inflammation of the cavernous sinus. Steroid therapy dramatically reverses the symptoms and clinical signs. Because they also may respond to steroids, tumors such as lymphoma and meningioma and orbital tumors can make differential diagnosis difficult. EXEGESIS: We report the case of a 78-year-old male patient in whom systemic lymphoma associated with inflammation of the cavernous sinus was uncovered by painful, gradually progressing, ophthalmoplegia mimicking Tolosa-Hunt syndrome. CONCLUSION: When faced with a clinical picture suggestive of the existence of Tolosa-Hunt syndrome clinical workup is mandatory and should lead to diagnosis of exclusion.

[Progressive multifocal leukoencephalopathy an chronic lymphocytic leukemia]. / Leucoencéphalopathie multifocale progressive et leucémie lymphoïde chronique.

INTRODUCTION: Progressive multifocal leukoencephalopathy is a demyelinating disease resulting from an opportunistic infection of the central nervous system by JC papovavirus. It mostly occurs in patients with an underlying immunosuppressive disorder. In the era of acquired immunodeficiency syndrome it is observed with increasing frequency. EXEGESIS: We report the case of a non-HIV-infected patient who presented chronic lymphocytic leukemia with progressive multifocal leukoencephalopathy uncovered by both imaging and the presence of JC virus in the cerebrospinal fluid. CONCLUSION: Due to the lack of specific treatment, the disease is still rapidly progressive and fatal.

[Ischemic cerebral vascular accident and zoster infection]. / Accident vasculaire cérébral ischémique et infection zostérienne.

Herpes zoster is uncommonly followed by cerebral infarction. The pathophysiological mechanism remains uncertain. Outcome is favorable after early specific treatment. We report the case of a 70-year-old woman who developed right hemiparesis with aphasia 15 days after thoracic herpes zoster. The herpes zoster induced cerebral vasculitis was hypothesized as no other etiology could be identified after detailed assessment of the cerebral infarction including brain MRI and cerebrospinal fluid study, and as the clinical course responded to antiviral therapy.

["MELAS" (A3243G) mutation of mitochondrial DNA: a study of the relationships between the clinical phenotype in 19 patients and morphological and molecular data]. / Mutation <> (A3243G) de l'ADN mitochondrial: étude chez 19 patients des relations entre le phénotype clinique, les données morphologiques et moléculaires.

Nineteen patients were found to harbor the mitochondrial DNA A3243G mutation associated with MELAS syndrome (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes). Eight of them had presented with stroke-like episodes and therefore had a clinical diagnosis of MELAS syndrome. The other 11 patients had no strokes and presented with generally less severe multisystemic disease. In the two groups, we compared muscle morphology, biochemical activities of muscle respiratory chain, and genetic characteristics: proportion and tissue distribution of the mutation, sequence of the 22 transfer RNA genes of the mitochondrial DNA. The proportion of mutant mtDNA in muscle was always greater than in blood. The number of patients in the two groups was too low to reach significant values. However, the patients with a MELAS syndrome presented with more severe respiratory chain abnormalities and with a proportion of the A3243G mutation that was both higher and more uniformly distributed among tissues. For symptoms others than stroke-like episodes, we did not observe any correlation with the level of mutant mtDNA in muscle. The analysis of the 22 tRNA sequences did not show differences between the two groups, and no co-inherited modifying tRNA genes could explain the variability of severity in our patients.