Effects of web-based adapted physical activity on hippocampal plasticity, cardiorespiratory fitness, symptoms, and cardiometabolic markers in patients with schizophrenia: a randomized, controlled study.

Among the lifestyle interventions, the physical activity (PA) has emerged as an adjuvant non-pharmacological treatment improving mental and physical health in patients with schizophrenia (SZPs) and increasing the hippocampus (HCP) volume. Previously investigated PA programs have been face-to-face, and not necessary adapted to patients' physiological fitness. We propose an innovative 16-week adapted PA program delivered by real-time videoconferencing (e-APA), allowing SZPs to interact with a coach and to manage their physical condition. The primary goal was to demonstrate a greater increase of total HCP volumes in SZPs receiving e-APA compared to that observed in a controlled group. The secondary objectives were to demonstrate the greater effects of e-APA compared to a controlled group on HCP subfields, cardiorespiratory fitness, clinical symptoms, cognitive functions, and lipidic profile. Thirty-five SZPs were randomized to either e-APA or a controlled group receiving a health education program under the same conditions (e-HE). Variables were assessed at pre- and post-intervention time-points. The dropout rate was 11.4%. Compared to the e-HE group, the e-APA group did not have any effect on the HCP total volumes but increased the left subiculum volume. Also, the e-APA group significantly increased cardiorespiratory fitness (VO2max), improved lipidic profile and negative symptoms but not cognitive functions. This study demonstrated the high feasibility and multiple benefits of a remote e-APA program for SZPs. e-APA may increase brain plasticity and improve health outcomes in SZPs, supporting that PA should be an add-on therapeutic intervention. ClinicalTrial.gov on 25 august 2017 (NCT03261817).

GeodesicSlicer: a Slicer Toolbox for Targeting Brain Stimulation.

NonInvasive Brain Stimulation (NIBS) is a potential therapeutic tool with growing interest, but neuronavigation-guided software and tools available for the target determination are mostly either expensive or closed proprietary applications. To address these limitations, we propose GeodesicSlicer, a customizable, free, and open-source NIBS therapy research toolkit. GeodesicSlicer is implemented as an extension for the widely used 3D Slicer medical image visualization and analysis application platform. GeodesicSlicer uses cortical stimulation target from either functional or anatomical images to provide functionality specifically designed for NIBS therapy research. The provided algorithms are tested and they are accessible through a convenient graphical user interface. Modules have been created for NIBS target determination according to the position of the electrodes in the 10-20 system electroencephalogram and calculating correction factors to adjust the repetitive Transcranial Magnetic Stimulation (rTMS) dose for the treatment. Two illustrative examples are processing with the module. This new open-source software has been developed for NIBS therapy: GeodesicSlicer is an alternative for laboratories that do not have access to neuronavigation system. The triangulation-based MRI-guided method presented here provides a reproducible and inexpensive way to position the TMS coil that may be used without the use of a neuronavigation system.

Social cognition in schizophrenia: Validation of an ecological fMRI task.

Neuroimaging studies have revealed brain regions involved in social cognition, which reportedly show functional alterations in schizophrenia. However, the social neural network has not been investigated with regards to language perception and social interactions in daily life. Here we developed and validated an integrative fMRI task to explore the neural basis of social cognition with regards to language perception in schizophrenia. The task comprised listening to film extracts and inferring mental states to characters. We first identified the functional network activated during the task in 28 healthy controls (HC). Next, we evaluated the reproducibility of Blood-Oxygen-Level Dependent (BOLD) variations in 14 HC participants. Finally, we investigated network impairment in 20 patients with schizophrenia (SZ) compared to HC. The HC group exhibited bilateral activation in the superior and middle temporal gyri (including the poles and the temporo-parietal junction). Overall, our novel integrative task induced activation of a functional network with good reproducibility and involved in language conveying social information. Compared to the HC group, the SZ group showed decreased recruitment of the right temporo-parietal junction. These findings may be useful for testing the impact of remediation on the brain, particularly on the network of language conveying social information.

Abnormalities of fronto-subcortical pathways in schizophrenia and the differential impacts of antipsychotic treatment: a DTI-based tractography study.

The fronto-striato-thalamic circuitry is a key network in patients with schizophrenia (SZPs). We use diffusion tensor imaging (DTI) to investigate the integrity of white matter (WM) pathways involved in this network in SZPs relative to healthy controls (HCs). We also evaluate the differential impact of chronic exposure to clozapine as well as other atypical and typical antipsychotics. 63 HCs and 41 SZPs were included. Of the SZPs, 16 were treated with clozapine (SZPsC), 17 with atypical antipsychotics (SZPsA), and 8 with typical antipsychotics (SZPsT). Three tracts were reconstructed in the left hemisphere using tractography: one fronto-subcortical tract, one prefronto-subcortical tract, and one prefronto-frontal tract. Diffusion parameters were individually extracted in each tract. SZPs exhibited lower integrity in both the fronto-subcortical and prefronto-subcortical tracts relative to HCs, and SZPsT showed altered integrity compared to SZPsC. There were no WM integrity differences in the prefronto-frontal tract between SZP groups or between SZPs and HCs. SZPs exhibit structural connectivity abnormalities in the prefronto-fronto-subcortical network that are specifically and differentially impacted by the type of antipsychotic treatment. Additional studies are needed to separate the contributions of clozapine-mediated neuroprotection, neurotoxicity related to typical antipsychotics, and the illness itself to observed differences.

Medical table: A major tool for antimicrobial stewardship policy.

Infectious diseases are unpredictable, with heterogeneous clinical presentations, diverse pathogens, and various susceptibility rates to anti-infective agents. These features lead to a wide variety of clinical practices, which in turn strongly limits their evaluation. We have been using a medical table since 2005 to monitor the medical activity in our department. The observation of heterogeneous therapeutic practices led to drafting up our own antibiotic guidelines and to implementing a continuous evaluation of their observance and impact on morbidity and mortality associated with infectious diseases, including adverse effects of antibiotics, duration of hospital stay, use of intensive care, and deaths. The 10-year analysis of medical practices using the medical table is based on more than 10,000 hospitalizations. It shows simplified antibiotic therapies and a reduction in infection-related morbidity and mortality. The medical table is a major tool for antimicrobial stewardship, leading to constant benefits for patients.

Impact of rTMS on functional connectivity within the language network in schizophrenia patients with auditory hallucinations.

This exploratory study investigated the functional connectivity (FC) in the language network in schizophrenia patients (SZ) with auditory verbal hallucinations (AVHs), and the therapeutic efficacy of rTMS on it. Eleven SZ with AVHs and 10 healthy controls (HC) underwent two fMRI sessions using a speech listening paradigm. SZ received 20Hz rTMS following the first fMRI session. Compared to HC, SZ showed a reduced FC in the language network. While AVHs improved after 12days, no changes in FC were observed. This suggests the efficacy of high-frequency rTMS on AVH without any impact for rTMS on FC within the language network.

Sphenoid fungus balls: clinical presentation and long-term follow-up in 24 patients.

Fungus balls are a non-invasive form of fungal infection involving the maxillary sinus in most cases. Sphenoid sinus fungus balls (SSFB) are rare and their clinical presentation is not well described. We intended to define the clinical presentation of sphenoid fungus balls, and retrospectively reviewed 24 cases of SSFB seen at our institution over a 10-year period, identified through pathological reports. Presenting symptoms were separated into three groups: headache, rhinological and asymptomatic. Headaches were subdivided into acute and chronic, unilateral and diffuse. Radiological clues leading to diagnosis were reviewed. Prognosis was determined from medical files or by phone calls. Sixty-seven per cent of patients were female. The mean age at presentation was 65 years. Sixty-two per cent presented with headache, 36% unilateral, mainly in the first trigeminal branch territory. Rhinological symptoms were seen in 21%. In 16% of patients the SSFB was asymptomatic and found during routine tests. SSFB, even if non-invasive, did lead to recurrent bacterial infections and central nervous system complications in three patients. Of 15 patients presenting with headache, 10 were significantly improved post surgery. The prognosis is good, with no recurrence of fungal infection after a main follow-up of 2.3 years. Our study underlines that SSFB present with headaches, often unilateral and in the fronto-orbital region. Proper imaging of the sphenoid sinus is useful in patients with unexplained headache. The neurologist has to be aware of radiological clues suggesting fungal sinus infection, since surgery is the main treatment, with good prognosis and frequent resolution of headaches.

Long term effects of azithromycin in patients with cystic fibrosis: A double blind, placebo controlled trial.

BACKGROUND: Macrolides display immunomodulatory effects that may be beneficial in chronic inflammatory pulmonary diseases. The aim of the study was to document whether long term use of azithromycin may be associated with respiratory benefits in young patients with cystic fibrosis. METHODS: A multicentre, randomised, double blind, placebo controlled trial was conducted from October 2001 to June 2003. The criteria for enrollment were age older than 6 years and forced expiratory volume in 1 second (FEV1) of 40% or more. The active group received either 250 mg or 500 mg (body weight < or > or =40 kg) of oral azithromycin three times a week for 12 months. The primary end point was change in FEV1. RESULTS: Eighty two patients of mean (SD) age 11.0 (3.3) years and mean (SD) FEV1 85 (22)% predicted were randomised: 40 in the azithromycin group and 42 in the placebo group. Nineteen patients were infected with Pseudomonas aeruginosa. The relative change in FEV1 at month 12 did not differ significantly between the two groups. The number of pulmonary exacerbations (count ratio 0.50 (95% CI 0.32 to 0.79), p < 0.005), the time elapsed before the first pulmonary exacerbation (hazard ratio 0.37 (95% CI 0.22 to 0.63), p < 0.0001), and the number of additional courses of oral antibiotics were significantly reduced in the azithromycin group regardless of the infectious status (count ratio 0.55 (95% CI 0.36 to 0.85), p < 0.01). No severe adverse events were reported. CONCLUSION: Long term use of low dose azithromycin in young patients with cystic fibrosis has a beneficial effect on lung disease expression, even before infection with Pseudomonas aeruginosa.

[Prospective epidemiological study on cutaneous melanomas in the Vendée area]. / Etude épidémiologique prospective des mélanomes cutanés en Vendée.

INTRODUCTION: The aim of this prospective study was to evaluate the incidence of melanoma in the Vendée area, coastal region of Eastern France, in 1997. PATIENTS AND METHODS: The 16 dermatologists in the Vendée area in 1997, grouped together in a local association, completed a sheet for each patient in whom a new melanoma had been diagnosed. During the same period, the hospital and private pathologists of the Vendée and surrounding areas reported their new cases of melanoma in patients residing at least six months of the year in the area. The data concerning the local population was supplied by the INSEE (French national institute of economic and statistical information) and the CPAM (French health authority) supplied data on the practitioners' activity. The raw and standardized incidence was calculated by the epidemiologist and the statistician of the local Vendée Cancer registry. RESULTS: One hundred fifteen new melanomas were diagnosed in Vendée in 1997, 97 by a dermatologist and 18 declared by a pathologist. There were 36 in situ and 79 invasive melanomas discovered in 68 women and 47 men (sex ratio: 1.46). The standardized rate of incidence according to the world model was of 98/100,000 for women and 7.8/100,000 for men. The frequency curve revealed two peaks: the first at 40-50 years of age and the second at 70-75. The mean Breslow index of the 79 invasive cancers was of 1.62 mm (range: 0.10-12.5 mm). The only statistically significant difference between the melanomas of the men and the women concerned the topography; there were more melanomas on the trunk in men and more melanomas on the lower limbs in the women. Forty-seven Dubreuilh melanomas were reported: 28 in situ and 19 invasive. DISCUSSION: This prospective study determined the incidence of melanoma in Vendée in 1997. The figures have been compared with those of the Vendée cancer registry, founded in April 1997, and with those of various published studies. The comparison was difficult because of the difference in study methodology. The only figures obtained in the same conditions are those of the cancer registry and we compared them with those of the Haut-Rhin, area of Eastern France: the incidence was similar for the women in the two areas and greater for the men in the Haut-Rhin with regard to the invasive melanomas. Conversely, 44 in situ melanomas were declared in the Haut-Rhin over a 3 year period versus 37 in Vendée over a period of 1 year. The increase in the incidence of melanoma in Vendée in the years to come should permit the evaluation of the impact of the various preventive campaigns.

[Prospective clinical study on new cutaneous melanomas in the Vendée area]. / Etude clinique prospective des nouveaux mélanomes en Vendée.

INTRODUCTION: In parallel to an epidemiological study on the new cases of melanoma reported in the Vendée area in 1997, private dermatologists conducted a clinical analysis of the characteristics of melanomas (including Dubreuilh's melanoma) and of the population concerned. PATIENTS AND METHODS: For each patient in whom a melanoma had been diagnosed, the dermatologists completed a standardized sheet that included the identification, phototype (comparing the distribution with that of the local population, studied in all the consultants during a randomly selected week), the personal and family history of melanoma, the existence of severe sunburn and exposure to artificial ultra-violet rays, the screening method, the time lapse before treatment, the impact of information campaigns, the number of nevi, atypical or not, and the characteristics of the tumor. The exeresis method and the histological characteristics (type, Clark's score and Breslow's index) were also noted. RESULTS: In 1997, the 16 local dermatologists diagnosed 97 melanomas in 55 women and 42 men with a mean age of 64 years. There was no statistically significant difference between the melanomas of the men and those of the women, other than their localization. Photoype II was significantly more frequent in the population exhibiting a melanoma. Sun exposure was moderate or intensive for three thirds of the patients. Past history of severe sunburn was twofold more frequent in the patients exhibiting a melanoma on the trunk. The association of many nevi was noted in a little more than half of the patients, and with atypical nevi in 5.2 p.cent. The elements that alerted the patients were recorded. The time lapse before diagnosis was calculated in months for nodular and in years for superficial melanomas. Clark's score and Breslow's index are presented in a table. DISCUSSION: Our study underlines several interesting features: the fairly high mean age on discovery, a high rate of invasive melanomas, and patients less well informed than in the Ile de France area. These results should open the debate on the best way to educate the population concerned so as to reduce the incidence of this malignant tumor.

Febrile and acute hyperthermia enhance TNF-induced necrosis of murine L929 fibrosarcoma cells via caspase-regulated production of reactive oxygen intermediates.

Previous studies have demonstrated the essential role of TNF-induced reactive oxygen intermediates (ROI) in the necrosis of L929 cells. We investigated the molecular basis for the interaction of hyperthermia and TNF in these cells. Hyperthermia, both febrile (40.0-40.5 degrees C) and acute (41.5-41.8 degrees C), strongly potentiated TNF killing, and sensistization was significantly quenched by the antioxidant, BHA. The broad-spectrum caspase inhibitor, Z-VAD, has been shown to markedly increase the TNF sensitivity of L929 cells at 37 degrees C; we observed that hyperthermia would also enhance the sensitivity of L929 cells to TNF + Z- VAD and that BHA could significantly quench the response, as well. The basis for hyperthermic potentiation was unlikely thermally-increased sensitivity to ROI, as treatment with hydrogen peroxide for 24 h killed L929 cells essentially equivalently, whether incubated continuously at 37 degrees C or at 40.0-40.5 degrees C, or for 2 h at 41.5-41.8 degrees C. However, febrile and acute hyperthermia markedly increased TNF-induced production of ROI, with or without Z-VAD. Hyperthermia dramatically accelerated the onset of this production, as well as the onset of necrotic death, as determined by oxidation of dihydro-rhodamine and propidium iodide staining, respectively, both of which were significantly quenchable with BHA. We conclude that hyperthermia potentiates TNF-mediated killing in this cell model primarily by increasing the afferent, and not the efferent, phase of TNF-induced necrosis.

Characterization of cytotoxicity induced by sphingolipids in multidrug-resistant leukemia cells.

Certain sphingolipids (SLs) exert fundamental roles in differentiative, growth-inhibitory and apoptotic pathways induced by a number of agents in leukemia cells. Multidrug-resistance (MDR) is a major cause of therapeutic failure in leukemia. SLs are among the diverse substrates for the MDR p-170 glycoprotein drug-efflux pump. We tested the hypothesis that expression of MDR would thereby block the cytotoxicity induced by the SLs sphingosine, sphinganine and N-hexanoyl-sphingosine. An MDR-expressing subline of murine P388 leukemia cells demonstrated an ED50 value > or = 2 log10 higher than the parental line in response to doxorubicin. In contrast, the ED50 values for each of the SLs were only approximately 1.5 to two-fold higher in the MDR line than in the parental; induction of DNA damage by SLs was comparable or actually greater in MDR compared to parental cells. Therefore, expression of MDR does not significantly affect the cytotoxic function of these SLs, nor do these SLs likely contribute to MDR.

[MRI and CT of parotid diseases in HIV-positive patients]. / IRM-et TDM de la pathologie parotidienne chez le patient VIH positif.

We report five cases of HIV patients with parotid pathology during a period of one year. All patients (4 men and 1 woman between the ages of 32 and 47 years) had a MRI or a CT confirmation of the parotid gland lesion. Three patients exhibited parotid gland cysts, one a nonspecific chronic inflammation and one an enlargement of the parotid gland with some benign lymphoepithelial lesions. Two patients underwent ultrasound-guided fine-needle aspiration biopsy. The cytology examination confirmed the benignity of the lesions. Finally, we expose the clinical management of parotid enlargements in HIV-positive patients.

Enhanced sensitivity of human colon tumor cell lines in vitro in response to thermochemoimmunotherapy.

We have investigated the cytotoxic responses in vitro of three human colon tumor cell lines with epithelial-like morphology, DLD-1, HCT-15, and HT-29, to thermochemoimmunotherapy with hyperthermia (42 degrees C for 2 h), carboplatin, and recombinant human tumor necrosis factor (TNF). Dose ranges of carboplatin and recombinant human TNF were administered essentially simultaneously and were followed 1 h later by hyperthermia. A two-tiered approach was used to evaluate cytotoxicity. In the first tier, a 5-day microcytotoxicity assay using vital dye staining was done; the effect on surviving fraction of simultaneously varying carboplatin and recombinant human TNF doses was evaluated by response surface methodology. From this analysis doses were selected for use in the second-tier clonogenic survival assays. A similar treatment protocol was used in clonogenic assays. Both assays revealed significant interline treatment response heterogeneity. Only the HCT-15 cells were sensitive to TNF alone; carboplatin activity against all three tumor cell lines was enhanced by TNF. Hyperthermia had minimal effect as a sole agent but enhanced the effects of carboplatin and TNF in DLD-1 and HCT-15 cells. Triple modality treatment resulted in 3-4-log decreased survival and could reduce cytotoxic resistance expressed against single- or dual-modality treatments by some of these cells.

Differential effects of glucocorticoids on the proliferation of a murine helper and a cytolytic T cell clone in response to IL-2 and IL-4.

The proliferation of murine T cell clones can be supported by IL-2 or by IL-4. We present here evidence that glucocorticosteroids differentially affect these two pathways of proliferation. Dexamethasone (DEX) and other corticosteroids were observed to induce autocrine proliferation of the D10.G4.1 Th cell clone (D10) in the presence of the anti-clonotypic antibody 3D3. This effect was inhibited by the anti-murine IL-4 antibody 11B11, indicating that it is mediated by IL-4. Furthermore, on this cell line, representative of the Th2 group of helper cells, DEX had little effect on the proliferation induced by exogenous IL-4 but completely inhibited the growth-promoting effects of IL-2. In contrast, the effects of DEX on the proliferation of the cytotoxic IL-2-dependent CTLL-2 cell line are completely opposite. DEX blocked the IL-4-driven proliferation of CTLL-2 cells, while leaving unaffected their response to IL-2. It is also shown in this study that the effects of glucocorticoids in this system are totally antagonized by the high affinity anti-glucocorticosteroid RU 38486, indicating that they are mediated through the described intracellular glucocorticoid receptor. These data suggest that the growth effects of IL-2 and IL-4 may be mediated by distinct pathways that are strikingly different in their sensitivity to glucocorticoids. In addition, the regulation of lymphokine-dependent proliferation and the response to glucocorticoids appeared very different in helper and cytotoxic cells.

[Hashimoto's thyroiditis and monoclonal gammapathy (two cases) (author's transl)]. / Thyroïdite d'Hashimoto et gammapathie monoclonale. Deux observations.

The authors describe two cases of Hashimoto's thyroiditis with a monoclonal dysproteinemia (IgG lambda in one case and IgG kappa in the other). They show that the antithyroid activity (anti-microsomial in the first case, anti thyroglobulin in the second case) is not carried by the abnormal gammaglobulin. The two diseases, therefore, appear to be separate but can both be considered as the consequence of a particular immunological state.