Altered B lymphocyte homeostasis and functions in systemic sclerosis

Beyond the production of autoantibodies, B-cells are thought to play a role in systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B-cells are a heterogeneous population with different subsets distinguished by their phenotypes and cytokine production. Data about B-cell subsets, cytokine production and intracellular pathways leading to this production are scarce in SSc. The aim of our study was to describe B-cell homeostasis, activation, proliferation, cytokine production in B-cells and serum and B-cell intracellular signaling pathways in SSc. We hypothezided that B-cell homeostasis and cytokine production were altered in SSc and could be explained by serum cytokine as well as by intracellular signaling pathway abnormalities.Forty SSc patients and 20 healthy controls (HC) were prospectively included. B-cell subsets were determined by flow cytometry using CD19, CD21, CD24, CD38, CD27, IgM and IgD. CD25, CD80, CD95, HLA-DR were used to assess B-cell activation. Intracellular production of IL-10 and IL-6 were assessed by flow cytometry after TLR9 and CD40 stimulation. IL-6, IL-10, Ki67, Bcl2 mRNA were quantified in B-cells. Cytokine production was also assessed in sera and supernatants of B-cell culture, using a multiplex approach. Signaling pathways were studied through phosphorylation of mTOR, ERK, STAT3, STAT5 using a flow cytometry approach.We found that SSc patients exhibited an altered peripheral blood B-cell subset distribution, with decreased memory B-cells but increased proportion of naive and CD21^LoCD38^Lo B-cell subsets. We observed an increased expression of activation markers (CD80, CD95, HLA-DR) on some B-cell subsets, mainly the memory B-cells. Secretion of IL-6, BAFF and CXCL13 were increased in SSc sera. There was no correlation between the peripheral blood B-cell subsets and the serum concentrations of these cytokines. After stimulation, we observed a lower proportion of IL-10 and IL-6 producing B–cells in SSc. Finally, we observed a significant decrease of mTOR phosphorylation in SSc patient B-cells.In conclusion, we observed an altered B-cell homeostasis in SSc patients compared to HC. Memory B-cells were both decreased and activated in patients. IL-10 producing B-cells were decreased in SSc. This decrease was associated with an alteration of mTOR phosphorylation in B-cells. Conversely, there was no correlation between serum cytokine profile and B-cell homeostasis alterations.     

A web-based Delphi study on the indications of chest radiographs for patients in ICUs

BACKGROUND: Strategies for ordering bedside chest radiographs (CXRs) have substantial logistic and financial consequences in the ICU. Many of the indications for CXRs in the ICU are controversial, such as the ordering of daily routine CXRs for intubated patients. The opinions of intensivists about ordering CXRs have not been reported. Comparing these opinions to established guidelines and identifying situations where opinions diverge in the absence of guidelines are of considerable interest. METHODS: We asked 190 intensivists from 34 ICUs in the area of Paris, France, to anonymously complete a 29-item questionnaire about their opinions regarding the ordering of CXRs; each item described a clinical scenario. Of the 29 scenarios, 10 dealt with the placement of medical devices, 8 with the presence of medical devices, and 11 with other clinical situations. The study was based on a Delphi process deployed over the Internet through an original software application. Three Delphi rounds were run between January and March 2006, using the same questionnaire. Detailed feedback for the answers given during the previous round was supplied to each intensivist solicited for updating his answers. RESULTS: Eighty-two intensivists from 32 ICUs completed the study. A consensus emerged that routine CXRs were necessary for eight scenarios and unnecessary for two scenarios. The study also shed light on items without a consensus. In particular, 75% of intensivists (58% on the first round) did not support obtaining daily routine CXRs in intubated patients. CONCLUSION: The study underlines situations in which intensivists do not support the guidelines and outlines recommendations likely to be followed in clinical practice.     

Intensity dependence of auditory evoked potentials during light interference in migraine

Abnormal decision-making (DM) performance has been reported in several neurobehavioral disorders such as schizophrenia, addiction, and obsessive compulsive disorders. The exploration of DM correlates in terms of symptom formation may add more knowledge about the meanings of DM performance in schizophrenia. We examined the Iowa Gambling Task (IGT) and its relationship with clinical symptoms, evaluated by Positive and Negative Symptom Scale (PANSS), in 40 schizophrenic patients and 20 controls. Schizophrenic patients did worse on IGT performance with a significant difference between the two groups in Net Score. PANSS positive symptoms were negatively correlated with Net Score and advantageous choices and directly with disadvantageous choices. Results suggest that persons with schizophrenia display a pattern of compromised DM related to positive symptoms.     

The circumventricular organs: an atlas of comparative anatomy and vascularization

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.     

Duration-dependent cytoprotective versus inflammatory effects of lung epithelial fibroblast growth factor-7 expression

Fibroblast growth factor-7 (FGF7) is a lung epithelial cell mitogen that is cytoprotective during injury. Transgenic mice that conditionally expressed FGF7 were used to dissect the mechanisms of FGF7 protection during lung injury. FGF7 improved survival when induced 3 days prior to acute lung injury. In contrast, FGF7 caused pulmonary inflammation and lung injury after 7 days or longer. Gene expression analysis of mouse lung mRNA identified mRNAs that contribute to the protective effects of FGF7. FGF7 improved survival during acute lung injury in adult mouse lung after short-term expression, but paradoxically induced inflammation and injury after persistent expression.     

Prevalence and characteristics of moderate to severe pulmonary hypertension in systemic sclerosis with and without interstitial lung disease

OBJECTIVE: To determine the prevalence and characteristics of moderate to severe pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) with and without interstitial lung disease (ILD). METHODS: We retrospectively studied clinical and functional characteristics of 197 consecutive patients with SSc who had undergone a screening echocardiography to detect PH. RESULTS: Moderate to severe PH was suspected in 36 patients (18.3%) and confirmed in 32 who underwent right heart catheterization. The prevalence of PH did not differ between patients with limited and patients with diffuse cutaneous SSc. PH was detected in 12/67 (17.9%) patients without ILD vs 24/110 (21.8%) patients with ILD (p not significant). In patients with ILD, a lower PaO2 appeared as the unique independent factor significantly associated with PH, regardless of the extent of fibrosis. In 3 patients out of 9 (33.3%) with ILD and significantly restrictive disease, PH was out of proportion to the degree of fibrosis. In patients with no ILD, a higher grade of dyspnea appeared as the unique independent factor associated with PH. In patients with no ILD, altered DLCO was the sole indicator of the pulmonary function tests associated with PH (best cutoff value 72%). DLCO correlated with systolic pulmonary arterial pressure only in patients with no ILD. CONCLUSION: Prevalence of moderate to severe PH was similar in SSc patients with and those without ILD. In patients with ILD, a lower PaO2 was the unique independent indicator associated with PH. In some patients with severe ILD, PH was out of proportion to the degree of fibrosis. A linear correlation between DLCO and systolic pulmonary arterial pressure was observed only in patients without ILD. All these indicators should assist identification of patients with or without ILD requiring diagnostic procedures for PH before annual screening.     

Aortic embolism of cement: a rare complication of lumbar percutaneous vertebroplasty

An aortic embolus of cement occurred in a 72-year-old woman after lumbar percutaneous vertebroplasty for breast cancer metastasis. A CT scan during the procedure revealed cement migration into the aorta via the lumbar artery. The cement embolus in the aorta, along with the hook-shaped cement fragment in the lumbar artery, was asymptomatic. Thereafter, a CT scan 4 months later still showed the presence of cement in the aorta and the lumbar artery at the level of the vertebroplasty. The patient is free of complaints after 4 months without anticoagulant treatment. This rare complication occurred because the collateral arterial supplies to the breast metastasis and the retrograde migration of cement during the vertebroplasty were not recognized. Proper techniques can minimize the risk of arterial embolism caused by cement during the procedure.     

Accuracy of 16-detector multislice spiral computed tomography in the initial evaluation of dilated cardiomyopathy

BACKGROUND: Multislice Computed Tomography (MSCT) recently proved its accuracy in the detection of coronary artery disease (CAD). It can also give information about left ventricular function and venous network anatomy. We here sought to validate a MSCT-based strategy in the initial evaluation of patients with dilated cardiomyopathy (DCM). METHODS: 36 patients with DCM underwent cardiac MSCT before conventional coronary angiography with ventriculography. We analysed arterial calcium score (Agatston score equivalent: ASE), coronary stenosis, left ventricular parameters and venous network. RESULTS: The sensitivity of a MSCT-based strategy in detecting significant CAD was 100% and the specificity 80%. The positive and negative predictive values were respectively 67% and 100%. For ASE <1.000 (75% of patients), MSCT detected all non-CAD patients without one (motion artifacts), enabling conventional angiography to be avoided in 21/27 patients (77.7%). For ASE > or =1000, MSCT enabled conventional angiography to be avoided in only 2/9 patients (22.2%). The ventricle was assessable in 83.4% (30 patients) on MSCT. Correlation coefficient Rs with ventriculography were 0.78 (p<0.0001), 0.77 (p<0.0001) and 0.82 (p<0.0001) respectively for end-diastolic volume, end-systolic volume and EF. The venous network was assessable in all patients both on MSCT and angiography. CONCLUSION: In patients undergoing an initial evaluation of DCM, MSCT appears to be an effective alternative to conventional angiography. The following attitude may be proposed: when ASE >1.000, conventional coronary angiography is mandatory due to MSCT's poor interest in such cases; when ASE <1.000, a contrast-enhanced MSCT may, when normal, replace coronary angiography.