Structural Connectivity and Cortical Thickness Alterations in Transient Global Amnesia.

BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is a sudden onset of anterograde and retrograde amnesia. We aimed to assess differences in terms of cortical thickness and structural brain connectome between patients with TGA (at acute and delayed postrecovery stages) and matched controls. MATERIALS AND METHODS: We report on 18 consecutive patients with TGA who underwent 3T MR imaging, including DTI and MPRAGE sequences, at the acute (mean delay postonset: 44 hours) and delayed post-recovery (mean delay: 35 days) stages. Structural connectome was assessed in patients with TGA and in 18 age- and sex-matched controls by using probabilistic fiber- tracking and segmentation of 164 cortical/subcortical structures ("nodes"). Connectivity graphs were computed and global network metrics were calculated. Network-based statistical analysis (NBS) was applied to compare patients with TGA at each stage with controls. We also compared cortical thickness between patients with TGA and healthy controls. RESULTS: Global network metrics were not altered in patients with TGA. NBS-analysis showed structural connectome alterations in patients with TGA compared with controls, in core regions involving the limbic network, with 113 nodes and 114 connections (33 left intrahemispheric, 31 right intrahemispheric, and 50 interhemispheric connections) showing significantly decreased structural connectivity (P < .05 NBS corrected, t-values ranging from 3.03 to 8.73). Lower cortical thickness compared with controls was associated with these structural alterations in patients with TGA, involving the orbitofrontal, cingulate, and inferior temporal cortices. All the abnormalities were visible at both acute and delayed postrecovery stages. CONCLUSIONS: Our preliminary study suggests there are structural abnormalities of the limbic network in patients with TGA compared with controls, including decreased structural connectivity and cortical thickness.

MRI of the cervical spinal cord predicts respiratory dysfunction in ALS.

For patients with amyotrophic lateral sclerosis (ALS), the primary therapeutic goal is to minimize morbidity. Non-invasive ventilation improves survival. We aim to assess whether Magnetic Resonance Imaging (MRI) of the cervical spinal cord predicts the progression of respiratory disorders in ALS. Brain and spinal MRI was repeatedly performed in the SOD1G86R mouse model, in 40 patients and in healthy controls. Atrophy, iron overload, white matter diffusivity and neuronal loss were assessed. In Superoxide Dismutase-1 (SOD1) mice, iron accumulation appeared in the cervical spinal cord at symptom onset but disappeared with disease progression (after the onset of atrophy). In ALS patients, the volumes of the motor cortex and the medulla oblongata were already abnormally low at the time of diagnosis. Baseline diffusivity in the internal capsule was predictive of functional handicap. The decrease in cervical spinal cord volume from diagnosis to 3 months was predictive of the change in slow vital capacity at 12 months. MRI revealed marked abnormalities at the time of ALS diagnosis. Early atrophy of the cervical spinal cord may predict the progression of respiratory disorders, and so may be of value in patient care and as a primary endpoint in pilot neuroprotection studies.

Spectrally-resolved measurement of concentrated light distributions for Fresnel lens concentrators.

A test method that measures spectrally resolved irradiance distribution for a concentrator photovoltaic (CPV) optical system is presented. In conjunction with electrical I-V curves, it is a means to visualize and characterize the effects of chromatic aberration and nonuniform flux profiles under controllable testing conditions. The indoor characterization test bench, METHOD (Measurement of Electrical, Thermal and Optical Devices), decouples the temperatures of the primary optical element (POE) and the cell allowing their respective effects on optical and electrical performance to be analysed. In varying the temperature of the POE, the effects on electrical efficiency, focal distance, spectral sensitivity, acceptance angle and multi-junction current matching profiles can be quantified. This work presents the calibration procedures to accurately image the spectral irradiance distribution of a CPV system and a study of system behavior over lens temperature.

The value of novel MRI techniques in Parkinson-plus syndromes: diffusion tensor imaging and anatomical connectivity studies.

Conventional MRI is a well-described, highly useful tool for the differential diagnosis of degenerative parkinsonian syndromes. Nevertheless, the observed abnormalities may only appear in late-stage disease. Diffusion tensor imaging (DTI) can identify microstructural changes in brain tissue integrity and connectivity. The technique has proven value in the differential diagnosis of multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and Parkinson's disease (PD). Here, we performed a systematic review of the literature on the main corticosubcortical DTI abnormalities identified to date in the context of the diagnosis of MSA and PSP with diffusion-weighted imaging, diffusion tensor imaging and anatomical connectivity studies. In good agreement with the histological data, increased diffusivity in the putamen (in MSA and PSP), in the middle cerebellar peduncles (in MSA) and in the upper cerebellar peduncles (in PSP) has been reported. Motor pathway involvement is characterized by low fraction anisotropy (FA) in the primary motor cortex in MSA-P and PSP, a high apparent diffusion coefficient (ADC) and low FA in the supplementary motor area in PSP. We then outline the value of these techniques in differential diagnosis (especially with respect to PD). Anatomical connectivity studies have revealed a lower number of fibers in the corticospinal tract in MSA and PSP (relative to PD and controls) and fewer tracked cortical projection fibers in patients with PSP or late-stage MSA (relative to patients with early MSA or PD and controls). Lastly, we report the main literature data concerning the value of DTI parameters in monitoring disease progression. The observed correlations between DTI parameters on one hand and clinical scores and/or disease duration on the other constitute strong evidence of the value of DTI in monitoring disease progression. In MSA, the ataxia score was correlated with ADC values in the pons and the upper cerebellar peduncles, whereas both the motor score and the disease duration were correlated with putaminal ADC values. In conclusion, DTI and connectivity studies constitute promising tools for differentiating between "Parkinson-plus" syndromes.

Pulse-triggered DTI sequence with reduced FOV and coronal acquisition at 3T for the assessment of the cervical spinal cord in patients with myelitis.

BACKGROUND AND PURPOSE: DTI is a promising technique for imaging of the spinal cord, but the technique has susceptibility-induced artifacts. We evaluated a pulse-triggered DTI sequence with an rFOV technique and coronal acquisition for the assessment of the cervical spinal cord in patients with myelitis at 3T. MATERIALS AND METHODS: A rFOV acquisition was established by a noncoplanar application of the excitation and the refocusing pulse in conjunction with outer volume suppression. The DTI sequence was performed in the coronal plane in 12 healthy volunteers and 40 consecutive patients with myelitis. Probabilistic tractography of the posterior and lateral funiculi was performed from the C1 to C7 levels. FA, MD, aD, rD, and ratios of aD and rD were measured. RESULTS: In healthy volunteers, mean DTI indices within the whole-fiber pathways were the following: FA = 0.61, MD = 1.17 × 10(-3) mm(2)/s, aD = 1.96 × 10(-3) mm(2)/s, rD = 0.77 × 10(-3) mm(2)/s, and ratios of aD and rD = 2.5. Comparison of healthy controls and patients with myelitis identified statistically significant differences for all DTI parameters. Different patterns of myelitis, including spinal cord atrophy and active inflammatory lesions, were recognized. There was a significant correlation between clinical severity and DTI parameters. CONCLUSIONS: The present work introduces a new approach for DTI of the cervical spinal cord at 3T, enabling a quantitative follow-up of patients with myelitis.

The SK3/K(Ca)2.3 potassium channel is a new cellular target for edelfosine.

BACKGROUND AND PURPOSE: The 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (edelfosine) is an ether-linked phospholipid with promising anti-cancer properties but some side effects that preclude its full clinical therapeutic exploitation. We hypothesized that this lipid could interact with plasma membrane ion channels and modulate their function. EXPERIMENTAL APPROACH: Using cell migration-proliferation assays, patch clamp, spectrofluorimetry and ¹²5I-Apamin binding experiments, we studied the effects of edelfosine on the migration of breast cancer MDA-MB-435s cells, mediated by the small conductance Ca²(+) -activated K(+) channel, SK3/K(Ca)2.3. KEY RESULTS: Edelfosine (1 µM) caused plasma membrane depolarization by substantially inhibiting activity of SK3/K(Ca)2.3 channels, which we had previously demonstrated to play an important role in cancer cell migration. Edelfosine did not inhibit ¹²5I-Apamin binding to this SK(Ca) channel; rather, it reduced the calcium sensitivity of SK3/K(Ca)2.3 channel and dramatically decreased intracellular Ca²(+) concentration, probably by insertion in the plasma membrane, as suggested by proteinase K experiments. Edelfosine reduced cell migration to the same extent as known SK(Ca) channel blockers. In contrast, K+ channel openers prevented edelfosine-induced anti-migratory effects. SK3 protein knockdown decreased cell migration and totally abolished the effect of edelfosine on MDA-MB-435s cell migration. In contrast, transient expression of SK3/K(Ca)2.3 protein in a SK3/K(Ca)2.3-deficient cell line increased cell migration and made these cells responsive to edelfosine. CONCLUSIONS AND IMPLICATIONS: Our data clearly establish edelfosine as an inhibitor of cancer cell migration by acting on SK3/K(Ca)2.3 channels and provide insights into the future development of a new class of migration-targeted, anti-cancer agents.

Na(V)1.5 enhances breast cancer cell invasiveness by increasing NHE1-dependent H(+) efflux in caveolae.

Na(V)1.5 sodium channels enhance the invasiveness of breast cancer cells through the acidic-dependent activation of cysteine cathepsins. Here, we showed that the Na(+)/H(+) exchanger type 1 (NHE1) was an important regulator of H(+) efflux in breast cancer cells MDA-MB-231 and that its activity was increased by Na(V)1.5. Na(V)1.5 and NHE1 were colocalized in membrane rafts containing caveolin-1. The inhibition of Na(V)1.5 or NHE1 induced a similar reduction in cell invasiveness and extracellular matrix degradation; no additive effect was observed when they were simultaneously inhibited. Our study suggests that Na(V)1.5 and NHE1 are functionally coupled and enhance the invasiveness of cancer cells by increasing H(+) efflux.

Cardioprotection by omega-3 fatty acids: involvement of PKCs?

It has been known since the 1970s that an increased consumption of n-3 long chain polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid has cardioprotective effects. Epidemiological studies have reported that this effect is due to the prevention of the arrhythmias responsible for sudden cardiac death. Mechanistically, different hypotheses have been put forward to give an explanation. Among them, there are a direct effect of the polyunsaturated fatty acids on ion channels and/or a modification of the regulation of ion channels by protein kinase C's.

[Value of MRI in symptomatic patients treated with tamoxifen]. / Apport de l'IRM chez les patientes symptomatiques traitées par tamoxifène.

PURPOSE: To assess the MR imaging (MRI) findings in symptomatic tamoxifen treated-women with abnormal transvaginal sonography. PATIENTS AND METHODS: From january 1997 to june 2000, 32 consecutive symptomatic tamoxifen treated-women with abnormal transvaginal sonography were prospectively studied by MRI. T1-weighted, T2-weighted, post-contrast T1-weighted and dynamic gradient-echo T1-weighted sequences were used. All patients underwent uterine sampling within one month of MRI. RESULTS: Endometrial thickness at sonography ranged from 5 to 48 mm (mean thickness 19 mm), and on T2-weighted imaging ranged from 3 to 50 mm (mean=25 mm). Three MRI patterns were found. Pattern 1 (13 patients) was defined as homogeneous high signal intensity of the endometrium on T2W images, and signal void in the lumen on gadolinium-enhanced images. Pattern 2 (8 patients) was defined as heterogeneous endometrial signal on T2W images, and latticelike enhancement traversing the endometrial canal on gadolinium-enhanced images. Pattern 3 (11 patients) was defined as heterogeneous signal on T2W images with masses or nodules which were better seen on dynamic gadolinium-enhanced images. In pattern 1 we found 13 atrophic endometrium, in addition there were 4 polypoid glandulo-cystic proliferation (PGCP), and 1 adenomyosis. In pattern 2 we found 3 PGCP, 4 atrophy and 1 polyp without hyperplasia. The 2 carcinomas and the polyps with hyperplasia were found in pattern 3 (11 patients). CONCLUSION: In our experience MRI allows differentiation of lesions which may require surgery from other lesions in which noninvasive follow-up is possible.

[Predictive value of abdominopelvic scan for optimal surgery of ovarian carcinoma]. / Travail original présenté lors de la Société Françaiseurgie d'oncologie Gynécologique des 5 et 6 novembre 1999. Valeur prédictive du scanner abdomino-pelvien pour la chirurgie optimale des carcinomes de l'ovaire.

BACKGROUND: Some patients undergo laparoscopy without optimal debulking surgery as initial treatment for advanced ovarian carcinoma. The amount of residual tumor following primary surgery is an important prognosis factor. Neoadjuvant chemotherapy is a new therapeutic approach. Secondary, optimal surgery could be done in better conditions. PURPOSE: To access the ability of preoperative abdominopelvic CT to predict success of debulking surgery for ovarian carcinoma: less than 1cm of residual tumor size after initial surgery. MATERIALS AND METHODS: We reviewed 39 patients (two stage Ic, 1 stage IIc, 22 stage III and 14 stage IV) operated on for ovarian carcinoma between January 1992 and December 1997. Surgical criteria of inability to perform optimal surgical cytoreduction were compared with abdominopelvic CT done the month before. CT scans were prospectively assessed by radiologist A and retrospectively (3 months to 6 years delay) reviewed separately by radiologists A and B without surgical data. RESULTS: Nineteen patients underwent optimal debulking surgery: 13 no residual tumor and 6 with residual lesions under 1cm. The interreader (0.73) and intrareader (0.9) agreement, worked out by Kappa coefficient, was judged good to very good. The sensitivity of CT was 91% with a specificity of 95%. CONCLUSION: These results allowed us to determine which CT criteria were accurate and reproducible to be a helpful for therapeutic choice and to avoid laparotomy without optimal surgery.

[Predictive value of preoperative abdominopelvic CT for optimal cytoreduction surgery in ovarian carcinoma]. / Valeur prédictive du scanner abdomino-pelvin pour la chirurgie optimale des carcinomes de l'ovaire.

Some patients underwent laparoscopy without optimal debulking surgery as initial treatment for advanced ovarian carcinoma. The amount of residual tumor following primary surgery was an important prognosis factor. Neoadjuvant chemotherapy is a new therapeutic approach. Secondary, optimal surgery could be done in better conditions. The purpose was to access the ability of preoperative abdominopelvic CT to predict success of debulking surgery for ovarian carcinoma: less than 1 cm of residual tumor size after initial surgery. We reviewed 39 patients (2 stages Ic, 1 stage IIc, 22 stages III and 14 stages IV) operated on for ovarian carcinoma between January 1992 and December 1997. Surgical criteria of inability to perform optimal surgical cytoreduction were compared with abdominopelvic CT done the month before. CT scans were prospectively assessed by radiologist A and retrospectively (3 months to 6 years delay) rewiewed separately by radiologists A and B without surgical data. Nineteen patients underwent optimal debulking surgery: 13 no residual tumor and 6 with residual lesions under 1 cm. The interreader (0.73) and intrareader (0.9) agreement, worked out by Kappa coefficient, was juged good to very good. The sensitivity of CT was 91% with a specificity of 95%. These results allowed us to determine wich CT criteria were accurate and reproducible to be a helpfull for therapeutic choice and to avoid laparotomy without optimal surgery.

[Computed tomography-guided transthoracic biopsy after negative fiber-optic endoscopy; apropos of 134 patients]. / Biopsies transthoraciques sous contrôle tomodensitométrique après fibroscopie négative; à propos de 134 patients.

PURPOSE: To evaluate the diagnostic accuracy of transthoracic needle biopsy (TNB) in patients being treated for cancer in order to compare results from small and large pulmonary nodules and to study the efficiency of pathology versus cytology analysis. PATIENTS AND METHODS: 141 consecutive CT-guided TNBs were performed in 134 patients. Cancer had been diagnosed in all cases. From the CT images, nodules were classified as small (< or = 15 mm) (n = 63; 47%) or large (> 15 mm) (n = 71; 53%). RESULTS: There were 16 benign and 118 malignant lesions (92 metastasis, 18 primary, 8 unspecified). There was no statistically significant difference for sensitivity and for prevalence of pneumothorax between small or large nodules. For the 107 true-positive and 16 true-negative results, the cytology examination was positive alone in 41 cases (33.3%), the pathology examination in 24 cases (19.5%) and both in 58 cases (47.2%). CONCLUSION: The diagnostic efficiency of CT-guided transthoracic needle biopsy is as good for small pulmonary nodules (> or = 15 mm) as for larger lesions. This technique is particularly useful in the diagnosis of secondary lesions and does not increase the risk of complications, even in case of small nodules. Ordering both pathology and cytology examinations improves the efficacy of TNB.

Multi-parameter observation of environmental asbestos pollution at the Institut de Physique du Globe de Paris (Jussieu Campus, France).

An original multi-parameter system has been used to study the nature of dust in the ambient air, particularly the total fibers and asbestos fibers, in eight areas of the Institut de Physique de Globe de Paris (France). These analyses provide a detailed case study of environmental pollution by asbestos fibers at low levels. The levels of total fibers with a length greater than 3 microns, measured with a real time fiber analyser monitor (FAM), give a baseline of 2.5 fibers per l., throughout the duration of sampling. The same levels, calculated during periods of effective presence of staff, are smaller than 10 fb per l. During these periods, the instantaneous value can show high peaks, reaching a maximum of 60 fb per l., but more often of about 5 to 10 fb per l. A direct cause and effect relationship exists between fiber concentrations and the presence of people, and indirectly with the variation of the other environmental parameters (temperature, humidity, air velocity). The baseline concentration of asbestos fibers, determined by analytical transmission electron microscopy (ATEM), is about 10(-1) fb per l., with a mean value during the presence of people always less than 1.5 fb per l. The low levels of asbestos fibers do not allow us to establish a precise correlation between the concentration of total fibers and the asbestos concentration, but a rough estimate suggests that asbestos could represent 10-20% of the airborne fibers monitored with the FAM. The statistical study of fiber sizes shows that 70 and 55% of analyzed chrysotile and amosite fibers respectively are smaller than 5 microns. These numbers are 40 and 35% for fibers smaller than 3 microns, which are undetected by the FAM. Amosite, which characterizes most of the asbestos-containing materials (ACM) in the analyzed areas, is detected in the ambient air in quantities ten times less important than chrysotile. The low asbestos levels and the difference between the nature of building asbestos and airborne fibers, show that the mean measured asbestos contents in the ambient air represent the geochemical background of chrysotile asbestos fibers in the Parisian air.

[Comparative study of tumor evaluation with computerized tomography and surgery in ovarian cancer]. / Etude comparative de l'évaluation tumorale par TDM et par chirurgie dans le cancer de l'ovaire.

PURPOSE: To evaluate the results of an abdomino-pelvic scan in cancers of the ovary in comparison with surgery. MATERIAL AND METHODS: We reviewed the observations concerning patients operated on for malignant tumors of the ovary between January 1992 and April 1995 in our anti-cancer center. We selected 32 patients who had had both a complete surgical abdominal exploration (laparotomy or laparoscopy) and an abdominal pelvic scan in the preceding months. We divided the abdomen into 33 areas and compared the scan of each with the surgical findings. Two cancer radiologists, including one gynecology specialist, studied the imaging separately. Neither knew the results of the surgical observations. RESULTS: Imaging findings varied with localization tumor size and presence or not of ascites radiologists. For certain localization, detection of lesions was difficult for both readers (pancreas, spleen, stomach), for others, recognition improved with experience (bowel, diaphragm, colon). CONCLUSION: The clinician must be aware of the variability of ovarian cancer assessment by CT scan, particularly if imaging alone is being used to guide treatment.

Regulation of Na+/H+ exchanger gene expression: mitogenic stimulation increases NHE1 promoter activity.

We examined factors important in regulation of expression of the Na+/H+ exchanger gene in NIH/3T3 cells. A stable fibroblast cell line was generated that contained a 1.1-kb proximal fragment of the mouse NHE1 promoter. The addition of serum to serum-starved cells resulted in an increase in activity of the NHE1 promoter. The mitogenic agonists insulin, thrombin, and epidermal growth factor also increased transcription from the NHE1 promoter. Phorbol esters also increased NHE1 promoter-directed transcription, whereas the serine/threonine protein kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine inhibited this stimulation. The protein kinase inhibitors GF-109203X, PD-98059, and genistein all stimulated promoter activity. Promoter deletion analysis and gel mobility shift assays showed that a region between 0.9 and 1.1 kb from the start site was involved in mediating the effect of mitogenic stimulation. The results show that a variety of mitogenic factors can activate the NHE1 promoter during cell growth and proliferation.

Long-term supplementation of culture medium with essential fatty acids alters alpha-linolenic acid uptake in Caco-2 clone TC7.

We investigated the influence of four different culture media: 20% fetal bovine serum (FBS), 5% FBS, 5% FBS supplemented with 10 mg x L(-1) linoleic acid (18:2(n-6)) or alpha-linolenic acid (18:3(n-3)) on alpha-linolenic acid apical uptake in clone TC7 of human intestinal Caco-2 cell line. Neither cellular viability nor cell monolayer integrity and permeability were altered by the four culture conditions. Our results show that the different culture media led to changes in alpha-linolenic acid maximal rate of uptake (Vmax) but did not alter the apparent transport constant (Km). Reducing FBS concentration from 20% to 5% increased significantly the rate of alpha-linolenic acid uptake, which was further increased by supplementation of the medium with 18:2(n-6) or 18:3(n-3). Supplementation with essential fatty acids led to a marked enrichment of brush-border membrane phospholipids in polyunsaturated fatty acids of the corresponding series and decreased significantly the levels of monounsaturated fatty acids. Saturated fatty acids, unsaturation index, and cholesterol/fatty acid ratios were unchanged. No clear relation could be established between the changes in membrane lipid composition and the alterations of alpha-linolenic acid uptake. These results indicate a weak influence of membrane lipid composition in the modulation of the uptake. Therefore, the increase of uptake following long-term supplementation of TC7 cells with essential fatty acids could be attributed to an increase of the expression of membrane protein(s) involved in the apical uptake of long-chain fatty acids. This remains to be established.

Use of the Modified Mini-Mental State Examination with children.

The validity and reliability of the modified version of the Mini-Mental State Examination with children was examined. The Modified Mini-Mental State Examination was administered to 99 children between 4 and 12 years of age (45 males and 54 females) to assess expected scores for nonclinical children and with a clinical sample. Concurrent validity was assessed through correlations of Modified Mini-Mental State Examination scores with Wechsler Intelligence scores and Child Behavior Checklist scores. The Modified Mini-Mental State Examination was administered to 26 children on two occasions to determine test-retest reliability. Means and standard deviations of scores are reported by age and grade level. Test-retest reliability coefficients were positively significant. For the nonclinical sample, Modified Mini-Mental State Examination scores were significantly and positively correlated with Verbal IQ and Child Behavior Checklist scores. Modified Mini-Mental State Examination scores were significantly correlated with Verbal IQ scores in the total and clinical samples.

Supplementation of MCF-7 cells with essential fatty acids induces the activation of protein kinase C in response to IGF-1.

The effects of changing the composition of membrane lipids on protein kinase C (PKC) activation were studied in MCF-7 human breast cancer cells. The supply of linoleate or alpha-linolenate to MCF-7 cells altered cell membranes fatty acid composition but did not affect PKC activity. When the cells were additionally exposed to IGF-1, the same fatty acids caused a dramatic increase in membrane-bound PKC activity. We also found that the mitogenic response induced by IGF-1 was not enhanced in those conditions when PKC becomes activated by linoleate and alpha-linolenate. These data show that these fatty acids elicit a distinct route for the transmission of IGF-1 signal by inducing the PKC pathway. They suggest that linoleate and alpha-linolenate could control the biological response of MCF-7 cells to IGF-1.