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91.
92.
Tamara Sauri àngel Izquierdo LLuis Ramió-Torrentà àngel Sanchez-Monta?ez Joaquim Bosch-Barrera Rut Porta 《JOURNAL OF CLINICAL NEUROLOGY》2015,11(1):87-91
Background
Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, symptoms of hypothalamic dysfunction, and seizures. It commonly precedes the diagnosis of cancer. Small-cell lung cancer is the neoplasm that is most frequently reported as the etiology underlying PLE.Case Report
This report describes a male patient who presented with neurologic symptoms consistent with anterograde amnesia, apathy, and disorientation. MRI revealed diffuse hyperintensities located predominantly in the medial bitemporal lobes, basal ganglia, frontal lobes, and leptomeninges on fluid attenuated inversion recovery images, suggesting PLE. Study of the primary tumor revealed squamous cell carcinoma of the lung. The patient was treated with neoadjuvant chemotherapy followed by surgery and adjuvant chemoradiotherapy, which resulted in his neurologic symptoms gradually improving.Conclusions
PLE might be a rare debut of squamous cell carcinoma of the lung. Treatment of the primary tumor may improve the neurologic symptoms. 相似文献93.
Siragusa S Anastasio R Porta C Falaschi F Pirrelli S Palmieri P Gamba G Granzow K Malato A Minardi V Tatoni P Bressan MA Mariani G 《Archives of internal medicine》2004,164(22):2477-2482
BACKGROUND: Treatment of patients with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) is problematic if diagnostic imaging is not immediately available. Pretest clinical probability (PCP) and D-dimer assessment can be used to identify patients for whom empirical protective anticoagulation is indicated. To evaluate whether PCP and D-dimer assessment, together with the use of low-molecular-weight heparins (LMWHs), allow objective appraisal of DVT and PE to be deferred for up to 72 hours, patients with suspected DVT and PE were prospectively examined. METHODS: Patients identified with a high PCP or a moderate PCP with positive D-dimer test results received a protective full-dose treatment of LMWH; the remaining patients were discharged without anticoagulant administration. However, all patients were scheduled to undergo objective tests for DVT or PE within 72 hours. Standard antithrombotic therapy was administered when deferred diagnostic tests confirmed venous thromboembolism. RESULTS: In total, 409 consecutive patients with suspected DVT and 124 with suspected PE were included in this study. A total of 23.8% (95% confidence interval [CI], 20.3%-27.3%) of patients had confirmed venous thromboembolism. At the short-term follow-up (72 hours), only a single thromboembolic event (0.2%; upper 95% CI, 0.6%) had occurred, whereas at the 3-month follow-up, 5 events (1.2%; 95% CI, 0.2%-2.1%) had occurred in patients in whom diagnosis of DVT or PE had previously been ruled out. None of the patients had major bleeding events. Ninety percent of patients were treated as outpatients. CONCLUSION: Our study demonstrates that this approach allows the safe deferral of diagnostic procedures for DVT and PE for up to 72 hours. 相似文献
94.
Anneline S. J. M. te Riele Cynthia A. James Brittney Murray Crystal Tichnell Nuria Amat-Alarcon Kathleen Burks Harikrishna Tandri Hugh Calkins Michael Polydefkis Daniel P. Judge 《Journal of cardiovascular translational research》2016,9(1):87-89
Prior reports have identified associations between SCN10A and cardiac disorders, such as atrial fibrillation and Brugada syndrome. We evaluated SCN10A in 151 probands with ARVD/C. In this cohort, 10 putatively pathogenic SCN10A variants were identified, including a novel frameshift insertion. Despite a known role for the encoded protein in peripheral nerve function, the proband with the frameshift variant had no discernible neurological abnormalities. Arrhythmic phenotypes were not different between those with a rare variant in SCN10A and those without. The prevalence of rare variants in SCN10A was similar among ARVD/C probands with and without a desmosome mutation and similar among healthy Caucasian controls. These results indicate the absence of a primary role for SCN10A mutations in ARVD/C. 相似文献
95.
G. Maconi E. Colombo P. Zerbi G.M. Sampietro P. Fociani M. Bosani A. Cassinotti V. Casini A. Russo S. Ardizzone M. Porta G. Bianchi Porro 《Digestive and liver disease》2005,37(6):418-423
OBJECTIVE: To determine the prevalence of cytomegalovirus infection in patients with steroid-refractory ulcerative colitis who required colonic resection, and to assess its possible association with the use of immunosuppressive and steroid treatment and outcome after colectomy. PATIENTS AND METHODS: The study included surgical specimens and related pre-operative endoscopic biopsy specimens of 77 consecutive ulcerative colitis patients (34 females) who underwent colectomy because of intractable steroid-refractory ulcerative colitis (55 patients), toxic megacolon (6 patients), dysplasia or cancer (7 patients) or loss of function of the colon (9 patients). Clinical features and current and past treatments were analysed. Haematoxylin and eosin and specific immunohistochemical staining for cytomegalovirus were used to detect inclusion bodies in all specimens. RESULTS: Cytomegalovirus infection was found in 15 of 55 steroid-refractory ulcerative colitis patients (27.3%) and in 2 of 22 non-refractory patients (9.1%) (p=0.123). Only six patients had positive staining for cytomegalovirus in pre-operative endoscopic biopsy specimens. Detection of cytomegalovirus inclusion in biopsy specimens was not related to the number of biopsies or to time that had elapsed since colonoscopy and index surgery. Cytomegalovirus-positive patients were more likely to be on systemic corticosteroids (p=0.03). In contrast, current use and duration of immunosuppressive treatment, number of steroid cycles since diagnosis and in the last year, as well as chronic use of steroid in the last year were not significantly related to cytomegalovirus infection. Cytomegalovirus-positive patients did not receive antiviral therapy following proctocolectomy but did not show endoscopic or histological cytomegalovirus reactivation in the ileo-anal pouch and in the remaining bowel. CONCLUSIONS: Cytomegalovirus infection is frequently found in surgical specimens of patients with steroid-refractory ulcerative colitis and is more likely in patients on corticosteroid treatment. Cytomegalovirus infection is frequently unrecognised in pre-operative biopsy specimens, thus raising concerns about the accuracy of the available diagnostic tools. Unrecognised and untreated cytomegalovirus infection does not affect the outcome of ulcerative colitis patients following proctocolectomy. 相似文献
96.
Biological and clinical relevance of matrix metalloproteinases 2 and 9 in acute myeloid leukaemias and myelodysplastic syndromes 总被引:1,自引:0,他引:1
Travaglino E Benatti C Malcovati L Della Porta MG Gallì A Bonetti E Rosti V Cazzola M Invernizzi R 《European journal of haematology》2008,80(3):216-226
We analysed by immunocytochemistry metalloproteinase (MMP)-2 and MMP-9 expression in bone marrow cells from 54 acute myeloid leukaemia (AML) patients, 153 myelodysplastic syndrome (MDS) patients, and 52 non-haemopathic subjects, in order to evaluate whether MMP expression abnormalities were associated with relevant laboratory or clinical findings. In normal samples MMP-2 was detected in rare myeloid cells, MMP-9 in most maturing myeloid cells. In MDS MMP-2 myeloid levels were higher than in controls (P < 0.0001); MMP-2 and MMP-9 were often co-expressed. Also many erythroblasts expressed MMP-2. There was a positive correlation between MMP-2 erythroblast expression and erythroid dysplasia (P = 0.002) and an inverse correlation between MMP-2 or MMP-9 myeloid expression and blast cell percentage (P = 0.05 and P = 0.04 respectively). High MMP levels in myeloid cells were associated with longer overall survival (P = 0.03) and evolution-free survival (P = 0.04). In AML MMP-2 levels were lower than in MDS (P < 0.0001) and MMP-9 levels lower than in MDS and controls (P < 0.0001). MMP levels did not predict response to therapy. The release of active MMPs was detected by colorimetric analysis in cell cultures from representative MDS and AML cases. In conclusion, we have demonstrated an abnormal MMP expression in AML as well as in MDS. The production and release of these enzymes may influence haematopoietic cell behaviour. In MDS, the detection of MMP deregulated expression may be important also from the clinical point of view: it may provide a useful tool for diagnosis, prognosis and a possible target for experimental treatments. 相似文献
97.
Alicia Calvo-Fernández Andrea Izquierdo Isaac Subirana Nuria Farré Joan Vila Xavier Durán Marcos García-Guimaraes Sandra Valdivielso Paula Cabero Cristina Soler Cora García-Ribas Clara Rodríguez Marc Llagostera Diana Mojón Miren Vicente Eduard Solé-González Andrea Sánchez-Carpintero Cristina Tevar Beatriz Vaquerizo 《Revista espa?ola de cardiología》2021,74(7):576-583
Introduction and objectivesCOVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19.MethodsWe included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT > 14 ng/L, the upper 99th percentile. Levels of NT-proBNP > 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV).ResultsCardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87).ConclusionsMyocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT. 相似文献
98.
Winck JC Vitacca M Morais A Barbano L Porta R Teixeira-Pinto A Ambrosino N 《Chest》2004,126(2):382-388
STUDY OBJECTIVES: To compare the tolerance and physiologic effects of a 5-night treatment with either nasal proportional assist ventilation (PAV) or pressure support ventilation (PSV) in patients with chronic ventilatory failure. DESIGN: Cross-over, randomized, controlled study. SETTING: Rehabilitation units of pneumology department. PATIENTS OR PARTICIPANTS: Four patients with COPD and 10 patients with restrictive thoracic diseases with chronic hypercapnia (median baseline Paco(2), 55.1 mm Hg) were studied. INTERVENTIONS: In a cross-over study, nasal PAV and PSV set at the patient's comfort were randomly applied during 5 consecutive nights (with a 2-night washout period). MEASUREMENTS AND RESULTS: Continuous nocturnal pulse oximetric saturation (Spo(2)) and arterial blood gas results at wake-up were evaluated at baseline during spontaneous breathing and on the fifth day of ventilatory support. Dyspnea, sleep quality, adaptation, and comfort at inspiration and expiration by visual analog scale (VAS) were evaluated every day as well as a side effects score. On the fifth day, there were no significant differences in daytime Paco(2) (median PAV, 53.3 mm Hg; median PSV, 50.2; p = 0.168). Mean nocturnal Spo(2) improved significantly with both PAV and PSV without any significant differences between modes (baseline median, 92%; PAV median, 94.5%; PSV median, 95%). The percentage of the study night spent < 90% Spo(2) (T90) was slightly but significantly higher with PAV than with PSV (median PAV T90, 4%; median PSV T90, 2%; p = 0.049). The VAS symptom score was similar at day 5 between modes; however, nasal and oral dryness were lower (p = 0.05) and alarm noise was higher (p = 0.037) with PAV. CONCLUSIONS: After 5 days of treatment, both modes had similar tolerance, and were equally effective in reducing daytime hypercapnia and improving nocturnal saturation and symptoms. However, PAV induced less nasal and oral dryness but was associated with higher alarm noise. 相似文献
99.
100.
Marianne Burbage Selina J. Keppler Francesca Gasparrini Nuria Martínez-Martín Mauro Gaya Christoph Feest Marie-Charlotte Domart Cord Brakebusch Lucy Collinson Andreas Bruckbauer Facundo D. Batista 《The Journal of experimental medicine》2015,212(1):53-72
The small Rho GTPase Cdc42, known to interact with Wiskott–Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization. Such severe immune deficiency is caused by multiple and profound B cell abnormalities, including early blocks during B cell development; impaired antigen-driven BCR signaling and actin remodeling; defective antigen presentation and in vivo interaction with T cells; and a severe B cell–intrinsic block in plasma cell differentiation. Thus, our study presents a new perspective on Cdc42 as key regulator of B cell physiology.B cells provide a critical line of defense from pathogenic infections through the production of highly specific antibodies. The initial stages of B cell development occur in the bone marrow, where hematopoietic stem cells undergo stepwise rearrangements of the genes encoding the B cell receptor (BCR) and changes in the expression of cell surface receptors (Hardy et al., 1991). Immature B cells egress the bone marrow and migrate to the spleen to complete their development, going through transitional stages. Mature follicular B cells then recirculate throughout the body in search for cognate antigen, continually entering secondary lymphoid organs, including the LNs and spleen. Specific recognition of antigen by the BCR provides the first signal required for B cell activation. Typically, a second signal is required for maximal activation and is provided by CD4+ helper T cells after the presentation of processed antigen on the B cell surface. These two signals in combination trigger the proliferation and differentiation of B cells, which go on to form antibody-secreting plasma cells and to establish germinal center responses for affinity maturation (Rajewsky, 1996).B cell activation in vivo is predominantly triggered by antigen on the surface of a presenting cell (Batista and Harwood, 2009). The prevalence of this mode of activation has brought about a reevaluation of the importance of the cytoskeleton, given that the recognition of tethered antigen requires considerable alteration in B cell morphology (Fleire et al., 2006). Antigen-induced BCR signaling leads to radical reorganization of the actin cytoskeleton resulting in the modification of the BCR dynamics at the cell surface (Hao and August, 2005; Treanor et al., 2010; Treanor et al., 2011). Moreover the binding of membrane-bound antigen to cognate BCR triggers a cascade of intracellular signaling events that induces actin-dependent spreading of the B cell across the antigen-containing surface (Weber et al., 2008; Sohn et al., 2008; Depoil et al., 2008). However the mediators that link BCR signaling with reorganization of the actin cytoskeleton are currently not well defined.Among actin regulators, the RhoGTPases are a highly conserved family that function as molecular switches by cycling between inactive GDP (guanosine diphosphate) and active GTP (guanosine triphosphate) bound states (Tybulewicz and Henderson, 2009). RhoGTPase activity is modulated by G-nucleotide exchange factors (GEF) that promote the formation of the GTP-bound state and binding to various effectors involved in actin reorganization. Conversely, GTPase-activating proteins (GAP) catalyze the hydrolysis of GTP and thereby switch off RhoGTPase activity. The importance of the RhoGTPases as a whole in the regulation of B cell responses is highlighted by the far-reaching consequences that impaired activity of several GEFs, such as Vav and DOCK8, has on humoral immune responses (Doody et al., 2001; Fujikawa et al., 2003; Randall et al., 2009; Zhang et al., 2009).The importance of Rho GTPases in B cell physiology has been well established. For example, RhoA has been shown to regulate BCR signaling by influencing inositol-3 phosphate synthesis and calcium signaling (Saci and Carpenter, 2005). Moreover, B cell–specific inactivation of both Rac1 and Rac2 leads to virtually complete absence of B cells (Walmsley et al., 2003), and inactivation of Rac1 results in defects in spreading in transitional cells (Brezski and Monroe, 2007). However, although the inactivation of Rac2 leads to defects in B cell adhesion and synapse formation, it is unclear whether these proteins are involved in actin-dependent spreading in mature B cells (Arana et al., 2008).Cdc42 has been little characterized in B cells, in spite of its proven chief role as an essential regulator of cell cycle (Johnson and Pringle, 1990), cell polarity (Etienne-Manneville, 2004), and actin cytoskeleton in other cellular systems. This is likely due, at least in part, to the reported mild phenotype of mice lacking Cdc42 in B cells (Guo et al., 2009) compared with the severe deficiencies observed in animals lacking Rac family members (Walmsley et al., 2003). However, the mild phenotype is somehow surprising given that Cdc42 directly or indirectly associates with Wiskott–Aldrich Syndrome Protein (WASp) and in complex with Arp2/3 regulates cytoskeleton remodeling (Symons et al., 1996; Aspenström et al., 1996; Kolluri et al., 1996). Importantly, mutations in WAS gene lead to a X-linked, recessive disease characterized by recurrent infections, abnormal lymphocyte function, as well as an increased risk for systemic autoimmunity (Derry et al., 1994; Sullivan et al., 1994). WASp deficient B cells play a primary role in driving autoimmunity (Becker-Herman et al., 2011). The Cdc42 effectors WASp and N-WASp have both been implicated the regulation of actin reorganization in response to BCR antigen engagement (Westerberg et al., 2012; Liu et al., 2013). Besides, expression of a dominant negative form of Cdc42 in B cells leads to alterations of the actin cytoskeleton (Westerberg et al., 2001). In addition, Cdc42 has been shown to play a role in the polarization and secretion of lysosomal protein involved in antigen extraction (Yuseff et al., 2011).Here, we used a strategy harnessing the mb1 promoter to generate mice with a selective and very effective deletion of Cdc42 in early B cell progenitors (Hobeika et al., 2006). Using this model, we demonstrated that Cdc42 plays an essential role in many aspects of B cell biology, including the formation of mature B cells and the establishment of antibody responses. We went on to dissect the underlying cause of the severe immunodeficiency of these mice and found that Cdc42-deficient B cells exhibit defects in BCR signaling and presentation of internalized antigen, leading to reduced B–T cell interactions and the absence of germinal center responses in vivo. Moreover, Cdc42-deficient B cells can normally proliferate and class switch when stimulated with CD40 or LPS, but they are completely impaired in their ability to differentiate into plasma cells. Together, these attributes render Cdc42-deficient mice unable to mount antibody responses after immunization with model antigen or viral infection, and highlight a fundamental role for this RhoGTPase in the regulation of B cell responses. 相似文献