RESUMO
Giant inflammatory pseudopolyps are begnin lesions that have been described usually in patients with inflammatory bowel disease. Rarely, they have been reported in patient without any colonic disease. We report the case of a 40-old woman, without previous colonic pathology, who presented with rectal giant inflammatory pseudopolyps revealed by rectal bleeding.
Les pseudo-polypes inflammatoires géants sont des tumeurs bénignes du tube digestif. Ils ont principalement été décrits chez les malades atteints de maladie inflammatoire chronique de l'intestin. Exceptionnellement, ils ont été rapportés chez des patients n'ayant aucune pathologie digestive. Nous rapportons l'observation d'une patiente de 40 ans, présentant de multiples pseudo-polypes inflammatoires géants du rectum, en l'absence de toute autre pathologie colorectale, révélés par des rectorragies.
Assuntos
Hemorragia Gastrointestinal/etiologia , Pólipos Intestinais/complicações , Pólipos Intestinais/diagnóstico , Feminino , Hemorragia Gastrointestinal/diagnóstico , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/patologia , Pólipos Intestinais/patologia , Pessoa de Meia-Idade , Doenças Retais/complicações , Doenças Retais/diagnósticoRESUMO
BACKGROUND AND PURPOSE: Studies of the effects of nicotine on motor symptoms in Parkinson's disease (PD) brought out discordant results. The aim of the present study was to evaluate the efficacy and safety of high doses of transdermal nicotine on motor symptoms in PD. METHODS: Forty PD patients were randomly assigned to a treated and untreated arm in an open-label study. Treated patients received increasing doses of nicotine to reach 90 mg/day by 11 weeks. This dosage was maintained for 28 weeks (W39) and then reduced over 6 weeks. Final evaluation was performed 6 weeks after washout. The main outcome measure was the OFF-DOPA Unified Parkinson's Disease Rating Scale (UPDRS) motor score measured on video recordings by raters blinded to the medication status of the patients. RESULTS: There was no significant difference in OFF-DOPA UPDRS motor scores between the nicotine-treated and non-treated groups, neither at W39 (19.4 ± 9.3 vs. 21.5 ± 14.2) nor considering W39 differences from baseline (-1.5 ± 12.1 vs. +0.9 ± 12.1). The 39-item Parkinson's disease questionnaire scores decreased in nicotine-treated patients and increased in non-treated patients, but the difference was not significant. Overall tolerability was acceptable, and 12/20 treated patients reached the maximal dosage. CONCLUSIONS: High doses of transdermal nicotine were tolerated, but our study failed to demonstrate significant improvement in UPDRS motor scores. Improvement in unblinded secondary outcomes (UPDRS-II, UPDRS-IV, doses of l-DOPA equivalents) suggest a possible benefit for patients treated with nicotine, which should be confirmed in larger double blind, placebo-controlled studies.
Assuntos
Nicotina/administração & dosagem , Nicotina/uso terapêutico , Agonistas Nicotínicos/administração & dosagem , Agonistas Nicotínicos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Idoso , Antiparkinsonianos/uso terapêutico , Quimioterapia Combinada , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Inquéritos e Questionários , Adesivo Transdérmico , Resultado do TratamentoRESUMO
PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.
Assuntos
Prova Pericial , Controle de Infecções/normas , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/terapia , Guias de Prática Clínica como Assunto , Adolescente , Adulto , França , Humanos , Hospedeiro Imunocomprometido , Controle de Infecções/métodos , Infecções/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Literatura de Revisão como Assunto , Vacinação/normas , Adulto JovemRESUMO
Although renal transplantation using expanded criteria donors has become a common practice, immune responses related to immunosenescence in those kidney allografts have not been studied yet in humans. We performed a retrospective molecular analysis of the T cell immune response in 43 kidney biopsies from patients with acute T cell-mediated rejection including 25 from recipients engrafted with a kidney from expanded criteria donor and 18 from recipients grafted with optimal kidney allograft. The clinical, transplant and acute T cell-mediated rejection characteristics of both groups were similar at baseline. The expression of RORγt, Il-17 and T-bet mRNA was significantly higher in the elderly than in the optimal group (p = 0.02, p = 0.036, and p = 0.01, respectively). Foxp3 mRNA levels were significantly higher in elderly patients experiencing successful acute T cell-mediated rejection reversal (p = 0.03). The presence of IL-17 mRNA was strongly associated with nonsuccessful reversal in elderly patients (p = 0.008). Patients with mRNA IL17 expression detection and low mRNA Foxp3 expression experienced significantly more treatment failure (87.5%) than patients with no mRNA IL17 expression and/or high mRNA Foxp3 expression (26.7%; p = 0.017). Our study suggests that the Th17 pathway is involved in pathogenesis and prognosis of acute T cell-mediated rejection in recipients of expanded criteria allograft.
Assuntos
Aloenxertos/imunologia , Seleção do Doador , Rejeição de Enxerto/imunologia , Transplante de Rim , Células Th17/imunologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aloenxertos/metabolismo , Aloenxertos/patologia , Biomarcadores/metabolismo , Biópsia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Humanos , Interleucina-17/metabolismo , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Th17/metabolismo , Transplante HomólogoRESUMO
PURPOSE: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). METHODS: Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. CONCLUSION: These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.
Assuntos
Doenças Cardiovasculares/etiologia , Lúpus Eritematoso Sistêmico/complicações , Programas de Rastreamento/métodos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Medicina Baseada em Evidências , Prova Pericial , Guias como Assunto , Humanos , Fatores de Risco , Prevenção SecundáriaRESUMO
The clinical use of biotherapies in Parkinson disease already has 30 years' history. The transplantation of dopamine fetal cells in the striatum of advanced patients has proved to be relevant in some patients but randomized efficacy trials in the US have provided disappointing results. However, cell therapies might come back on stage with the use of stem cells in the future. Gene therapy is a more recent strategy relying on viral vectors able to transduce genes coding either for the enzymes that can increase neurotransmitters production or genes for trophic factors. Several approaches have been developed in PD and have been experimented in patients. Although, some of the studies have evidenced insufficient clinical benefit, other programs, such as those using dopamine replacement techniques are promising. We find fresh hope in this field that might be the future of PD treatment. It remains however that advanced PD might not be the ideal condition to properly benefit from biotherapies and there is a need of studies at earlier stages of the disease, a time where major change in the disease course might be expected.
Assuntos
Terapia Biológica/métodos , Doença de Parkinson/terapia , Animais , Transplante de Células/métodos , Dopamina/biossíntese , Terapia Genética/métodos , Humanos , Imunoterapia/métodos , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêuticoRESUMO
OBJECTIVES: To investigate differences between open and laparoscopic aortobifemoral bypass surgery for aorto-iliac occlusive disease on postoperative morbidity and mortality. DESIGN: A multicentre randomised controlled trial. METHODS: Between January 2007 and November 2009, 28 patients with severe aorto-iliac occlusive disease (TASC II C or D) were randomised between laparoscopic and open approach at one community hospital and one university hospital (TASC = Trans-Atlantic Inter-Society Consensus on the Management of Peripheral Arterial Disease). RESULTS: The operation time was longer for the laparoscopic approach (mean 4 h 19 min (2 h 00 min to 6 h 20 min) vs. 3 h 30 min (1 h 42 min to 5 h 11 min); p = 0.101)). Nevertheless, postoperative recovery and in-hospital stay were significantly shorter after laparoscopic surgery. Also oral intake could be restarted earlier (mean 20 h 34 min (6 h 00 min to 26 h 55 min) vs. 43 h 43 min (19 h 40 min to 77 h 30 min); p = 0.00014)) as well as postoperative mobilisation (walking) (mean 46 h 15 min (16 h 07 min to 112 h 40 min) vs. mean 94 h 14 min (66 h 10 min to 127 h 23 min); p = 0.00016)). Length of hospitalisation was shorter (mean 5.5 days (2.5-15) vs. mean 13.0 days (7-45); p = 0.0095)). Visual pain scores and visual discomfort scores were both lower after laparoscopic surgery. Also return to normal daily activities was achieved earlier. There were no major complications in both groups. CONCLUSION: Laparoscopic aortobifemoral bypass surgery for aorto-iliac occlusive disease is a safe procedure with a significant decrease in postoperative morbidity and in-hospital stay and earlier recovery.
Assuntos
Doenças da Aorta/cirurgia , Arteriopatias Oclusivas/cirurgia , Implante de Prótese Vascular , Artéria Ilíaca/cirurgia , Laparoscopia , Atividades Cotidianas , Idoso , Doenças da Aorta/mortalidade , Arteriopatias Oclusivas/mortalidade , Bélgica , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Constrição Patológica , Feminino , Hospitais Comunitários , Hospitais Universitários , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/mortalidade , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
Anatomical and biomechanical studies have shown that the anterior cruciate ligament (ACL) consists of two distinct bundles, the anteromedial (AM) and posterolateral. Each bundle has its specific role during the motion of the knee. ACL reconstruction techniques have focused on the restauration of the anteroposterior stability by substituting the more isometric AM bundle. Although these ligamentoplasties provide overall good results, in the last ten years double-bundle ACL reconstruction techniques have been developed, to better replicate the ligament anatomy. Despite the growing number of published studies, including randomized controlled trials comparing single bundle and double bundle reconstructions, there is still a lack of evidence of any superiority of the double-bundle technique. Furthermore, many series are criticized for their poor assessement of rotational stability, using most of the time subjective pivot shift clinical testing. Among the methods available to measure tibial rotation, 3-D optoelectronic evaluation is an attractive tool and has been used in some studies reporting rotational mesurements after ACL single-bundle reconstruction. Our Department of Orthopaedics and Traumatology has been using double-bundle techniques for a few years. We conducted a preliminary prospective randomized study, in order to compare single and double-bundle techniques by clinical and optoelectronic evaluations.
Assuntos
Ligamento Cruzado Anterior/cirurgia , Humanos , Procedimentos Ortopédicos/métodos , Estudos ProspectivosRESUMO
In the last years, several experimental biotherapies have been developed to treat Parkinson's disease. Initially, fetal dopaminergic transplants were proposed. Although a proof of concept and encouraging results have been provided, limitations of this treatment emerged over the years and the failure of controlled trials have conducted to a pause in the development of strategies based on fetal cells. Alternative approaches such as the use of retinal pigmented cells recently provided disappointing results in patients and much hope has now been reported on other sources of dopaminergic neurons such as those originating from stem cells. This strategy is however not yet ready for clinical trials in patients. Eventually, gene therapy is a new original experimental technique which has elicited several trials in the last few years some of them being promising.
Assuntos
Terapia Biológica/métodos , Doença de Parkinson/terapia , Transplante de Células/métodos , Dopamina/biossíntese , Células-Tronco Embrionárias , Terapia Genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Humanos , Doença de Parkinson/genética , Doença de Parkinson/cirurgia , Transplante de Células-TroncoRESUMO
Simultaneous cardiac and renal involvement is associated with a particularly poor prognosis in patients with AL amyloidosis (AL-A). We report the first case of a successful long-term outcome of combined heart and kidney transplantation not followed by autologous stem cell transplantation in a patient with systemic AL-A. The recipient was a 46-year-old man with end-stage renal failure associated with serious cardiac involvement in the context of AL-A. Before transplantation, two courses of oral melphalan plus prednisone induced partial hematologic remission, as shown by the decrease in circulating free light chain with no improvement of renal or heart function. The patient underwent combined heart and kidney transplantation as a rescue treatment. During the follow-up period (36 months), plasma cell dyscrasia remains in complete remission, with normal free lambda light chain levels and no recurrence of amyloid deposition on heart and kidney grafts. This case report demonstrates that combined heart and kidney transplantation not systematically associated with stem cell transplantation may be considered an additional therapeutic option in AL-A patients with severe organ dysfunction and partial hematologic remission.
Assuntos
Amiloidose/cirurgia , Transplante de Coração , Transplante de Rim , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
Minimal change nephrotic syndrome (MCNS) is described as a paraneoplastic manifestation of classical Hodgkin's lymphoma (cHL). We reassessed the pathophysiological and clinical significance of this association. A retrospective study was performed to evaluate a cohort of adult patients who developed MCNS and cHL. Twenty-one patients recruited in 15 French centers were analyzed. cHL was associated with inflammatory and general symptoms in most cases. The morphological subtype was predominantly nodular sclerosis (71.4%). MCNS appeared before the diagnosis of lymphoma in eight patients (38.1%) and in this case, it was characterized by a nephrotic syndrome (NS) frequently resistant (50%) or dependent (12.5%) to steroid treatment. Interestingly, diagnosis (3-120 months after MCNS) and effective treatment of the hemopathy were associated with the disappearance of the MCNS. cHL was diagnosed before MCNS in nine patients (42.9%), and in this case, glomerulopathy was associated with cHL relapse in 55.5% of cases. In four patients (19%), the two diseases occurred simultaneously. Extensive immunohistochemical study of lymph nodes was performed in eight patients and did not reveal particular features. In conclusion, MCNS associated with cHL is frequently dependent or resistant to steroid regimen, but remission of NS is obtained with the cure of lymphoma.
Assuntos
Doença de Hodgkin/patologia , Nefrose Lipoide/fisiopatologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Comorbidade , Citocinas/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , NF-kappa B/fisiologia , Nefrose Lipoide/tratamento farmacológico , Nefrose Lipoide/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Linfócitos T/patologia , Fatores de TempoRESUMO
OBJECTIVE: To assess the tolerance and efficacy of rituximab in patients with various autoimmune diseases seen in daily rheumatological practice. METHODS: 866 rheumatology and internal medicine practitioners were contacted by e-mail to obtain the files of patients treated with rituximab for systemic autoimmune diseases. Patients with lymphoma were analysed if the evolution of the autoimmune disease could be evaluated. RESULTS: In all, 43 of 49 cases could be analysed, including 14 with rheumatoid arthritis (RA), 13 with systemic lupus erythematosus (SLE), six with primary Sjogren's syndrome (pSS), five with systemic vasculitis, and five with other autoimmune diseases. Rituximab was prescribed for lymphoma in two patients with RA and two with pSS. In the 39 other cases, rituximab was given because of the refractory character of the autoimmune disease. The mean follow up period was 8.3 months (range 2 to 26). There were 11 adverse events in 10 patients and treatment had to be discontinued in six. Efficacy was observed in 30 patients (70%): RA 11, SLE 9, pSS 5, vasculitis 2, antisynthetase syndromes 2, sarcoidosis 1. The mean decrease in corticosteroid intake was 9.5 mg/d (range 0 to 50) in responders. Seven patients experienced relapse after mean 8.1 months (5 to 15). Three patients died because of refractory autoimmune disease. CONCLUSIONS: Despite absence of marketing authorisation, rituximab is used to treat various refractory autoimmune diseases in daily rheumatological practice. This study showed good tolerance and short term clinical efficacy, with marked corticosteroid reduction in patients with SLE, pSS, vasculitis, and polymyositis.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Síndrome de Sjogren/tratamento farmacológico , Resultado do Tratamento , Vasculite/tratamento farmacológicoRESUMO
Huntington's disease (HD) is a monogenic neurodegenerative disease that affects the efferent neurons of the striatum. The protracted evolution of the pathology over 15 to 20 years, after clinical onset in adulthood, underscores the potential of therapeutic tools that would aim at protecting striatal neurons. Proteins with neuroprotective effects in the adult brain have been identified, among them ciliary neurotrophic factor (CNTF), which protected striatal neurons in animal models of HD. Accordingly, we have carried out a phase I study evaluating the safety of intracerebral administration of this protein in subjects with HD, using a device formed by a semipermeable membrane encapsulating a BHK cell line engineered to synthesize CNTF. Six subjects with stage 1 or 2 HD had one capsule implanted into the right lateral ventricle; the capsule was retrieved and exchanged for a new one every 6 months, over a total period of 2 years. No sign of CNTF-induced toxicity was observed; however, depression occurred in three subjects after removal of the last capsule, which may have correlated with the lack of any future therapeutic option. All retrieved capsules were intact but contained variable numbers of surviving cells, and CNTF release was low in 13 of 24 cases. Improvements in electrophysiological results were observed, and were correlated with capsules releasing the largest amount of CNTF. This phase I study shows the safety, feasibility, and tolerability of this gene therapy procedure. Heterogeneous cell survival, however, stresses the need for improving the technique.
Assuntos
Terapia Genética/métodos , Doença de Huntington/genética , Doença de Huntington/terapia , Fármacos Neuroprotetores/farmacologia , Animais , Encéfalo/metabolismo , Linhagem Celular , Sobrevivência Celular , Fator Neurotrófico Ciliar/química , Fator Neurotrófico Ciliar/genética , Códon , Cricetinae , Eletrofisiologia , Feminino , Técnicas de Transferência de Genes , Humanos , Masculino , Neurônios/metabolismo , Polímeros/química , Retroviridae/genética , Fatores de TempoRESUMO
Since a few years, vascular surgeons are becoming interested in laparoscopic vascular techniques. After initial experience with the hand-assisted laparoscopic technique, we now adopt the totally laparoscopic approach for aortoiliac surgery. Our first case with this second technique is presented.
Assuntos
Implante de Prótese Vascular/métodos , Laparoscopia/métodos , Síndrome de Leriche/cirurgia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
In cirrhotic patients, esophageal and esophagogastric varices are the most common sites of bleeding, often responsible for hypovolemic shock. Hepatocellular carcinoma, blunt abdominal trauma and postprocedural complications are classical causes of hemoperitoneum in hepatic cirrhosis. Rupture of omental varices is another and rarely reported cause of shock in cirrhosis. We report a case of hypovolemic shock caused by ruptured omental varices. Selective review of literature regarding presentation, diagnosis and management of ruptured intraabdominal varices is also part of presentation.
Assuntos
Hemoperitônio/complicações , Cirrose Hepática/complicações , Omento/irrigação sanguínea , Omento/lesões , Choque/etiologia , Varizes/complicações , Hemoperitônio/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Omento/diagnóstico por imagem , Ruptura Espontânea/complicações , Tomografia Computadorizada por Raios X , Varizes/diagnóstico por imagemRESUMO
Fli and erg are two members of the ETS gene family that encodes transcription factors related to the c-ets-1 proto-oncogene. The products of the ETS genes act as transcriptional effectors in cell proliferation, differentiation, and oncogenic transformation. FLI and ERG, two closely-related proteins, bind, as do all the ETS proteins characterized so far, to DNA sequences with an invariable central GGA core flanked by preferred nucleotides. Nevertheless, promoter-specific responses to FLI or ERG may be driven by mechanisms involving multicomponent complexes. Using a yeast two-hybrid screen, we have identified several proteins that physically interact with either FLI or ERG proteins used as bait. The Xenopus developmentally implicated Xvent-2 and Xvent-2B proteins, and the Xenopus splicing factor RNP-C/U1C physically interact with Xl-FLI and Xl-ERG, both in the yeast two-hybrid system and in vitro. We also report the potential interaction of FLI and ERG with Sox-D, a stabilizing protein that may modulate their transcriptional activity. Furthermore, the possible involvement of the transcriptional effectors FLI and ERG in mRNA processing, hematopoiesis or in the control of angiogenesis is suggested through possible interactions with, respectively, RNA binding proteins and hnRNPs, a repressor of the hematopoietic pathway (SAP18), and the HAF protein.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas Proto-Oncogênicas , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Ligação Proteica , Proteína Proto-Oncogênica c-fli-1 , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Ribonucleoproteínas Nucleares Pequenas/genética , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Saccharomyces cerevisiae/genética , Transativadores/genética , Fatores de Transcrição/genética , Técnicas do Sistema de Duplo-Híbrido , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevisRESUMO
Spontaneous hemomediastinum is a rare event, occurring in association with bleeding disorders, intratumoral bleeding, or following an abrupt increase in intrathoracic pressure. We report the case of a patient with systemic lupus erythematosus, nephrotic syndrome, and renal failure, in whom mediastinal lipomatosis (ML) developed following increased corticosteroid therapy. Anticoagulant therapy likely precipitated a massive spontaneous hemomediastinum secondary to diffuse hemorrhage of mediastinal fat, which required emergency decompressive surgery. Steroid-induced ML is common and usually well tolerated, but clinicians should be aware of its potential risk of bleeding when associated with anticoagulant therapy. This case further emphasizes the bleeding complications of treatment with low-molecular-weight heparin in patients with renal failure.
Assuntos
Anticoagulantes/efeitos adversos , Glucocorticoides/efeitos adversos , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/efeitos adversos , Lipomatose/induzido quimicamente , Doenças do Mediastino/induzido quimicamente , Prednisona/efeitos adversos , Adulto , Feminino , HumanosRESUMO
BACKGROUND: A new Biopsy Index containing the Glomerular Activity (GAI), Tubulointerstitial Activity (TIAI), Chronic Lesion (CLI), and Immunofluorescence (IFI) indices was developed, showing better correlations with clinical and outcome parameters than the National Institutes of Health Activity and Chronicity Indices (AI and CI) in lupus nephritis. This report examines the ability of these indices and individual morphologic variables to predict doubling of serum creatinine (SCr; CRX2). METHODS: Renal biopsies from 71 patients with lupus nephritis with an initial biopsy (Bx1) and systematic control biopsy (Bx2) after six months of therapy were studied. Kaplan-Meier survival curves were developed for each index and morphologic variable at each biopsy. A subset of 30 biopsies was stained with the macrophage marker PGM1. RESULTS: At Bx1, only the TIAI and the quantity of C3 and vascular staining on IF were predictive of CRX2. At Bx2, particularly predictive of CRX2 were the GAI, IFI, Biopsy Index, and BxInfl, a composite variable comprised of all of the inflammatory variables. Among individual variables, glomerular and tubular macrophages correlated the best with clinical and outcome parameters. Crescents and karyorrhexis/fibrinoid necrosis also correlated with outcome. Neither the NIH CI or our CLI, nor the TIAI correlated with outcome. In 30 biopsies stained with PGM1, PGM1+ cells correlated well with glomerular and tubular macrophages identified on routine stains and showed even better correlations with SCr, proteinuria, and progression to renal insufficiency than the latter. A diffuse membranoproliferative (MPGN) pattern was seen in seven patients at Bx1. In four of the seven patients, MPGN disappeared with therapy, and all finished with normal renal function. However, among the three patients in whom MPGN persisted and eight patients in whom MPGN, focal or diffuse, appeared under therapy, six reached end-stage renal disease, and a seventh died with marked renal insufficiency. CONCLUSIONS: The biopsy index and its components correlate modestly with CRX2 at Bx1, but strongly at Bx2, particularly IFI, BxInfl, and glomerular and tubular macrophages. Stains for macrophage markers form a valuable adjunct in interpretation of renal biopsies in systemic lupus erythematosus (SLE). MPGN features do not have an ominous significance at Bx1, but their persistence or appearance under therapy are associated with poor outcome.
Assuntos
Rim/patologia , Nefrite Lúpica/patologia , Macrófagos/patologia , Adulto , Biópsia , Creatinina/sangue , Feminino , Glomerulonefrite Membranoproliferativa/sangue , Glomerulonefrite Membranoproliferativa/patologia , Humanos , Imuno-Histoquímica , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Valor Preditivo dos Testes , ReoperaçãoRESUMO
In the Xenopus laevis embryo, the overexpression of the Xl-FLI protein, a transcription factor of the ETS family, provokes severe developmental anomalies, which affect anteroposterior and dorsoventral polarities, optic cup formation, head cartilage morphogenesis, and erythrocyte differentiation. It has been proposed that these effects could be correlated to modifications of cell adhesion properties and/or to an increased engagement of cells in the apoptotic pathway during early development (Remy et al., Int. J. Dev. Biol. 40, 577-589, 1996). To address these questions, we have first analyzed the behavior of cells overexpressing the protein in both aggregation and adhesion assays. We observe perturbations of cell-cell interactions as well as perturbations of cell adhesion and spreading on fibronectin and extracellular matrix (ECM). Second, we have analyzed apoptosis of cells overexpressing the Xl-FLI protein, by testing DNA fragmentation, caspase-3 activity and by performing TUNEL assay. We show that Xl-Fli overexpression results in the appearance of hallmarks of apoptosis, including exclusion of cells from the interior of the embryo, internucleosomal fragmentation of DNA and dose-dependent induction of caspase-3, resulting in the hydrolysis of poly(ADP-ribose) polymerase. In addition, a dominant-negative mutation of BMPs receptors decreases the effects of Xl-Fli overexpression, suggesting that a modification of the BMP signalling could be responsible for increased apoptosis. The latter appears to affect predominantly ventral and ventrolateral regions of the embryo.
Assuntos
Apoptose , Proteínas de Ligação a DNA/biossíntese , Proteínas Proto-Oncogênicas , Transdução de Sinais , Transativadores/biossíntese , Animais , Caspase 3 , Caspases/biossíntese , Adesão Celular , Agregação Celular , Fragmentação do DNA , Proteínas de Ligação a DNA/genética , Indução Enzimática , Matriz Extracelular/metabolismo , Expressão Gênica , Marcação In Situ das Extremidades Cortadas , Nucleossomos , Proteína Proto-Oncogênica c-fli-1 , Transativadores/genética , Xenopus laevis/embriologiaRESUMO
BACKGROUND: Various morphologic indices for the evaluation of renal biopsies in lupus nephritis have been developed, of which the most successful have been the NIH Activity Index (AI) and Chronicity Index (CI). We wished to develop a biopsy index from standard light and immunofluorescence (IF) material that would correlate yet more closely with clinical and outcome parameters than the current indices, and be applicable to both treated and untreated cases. METHODS: A cohort of 71 patients with lupus nephritis who had initial renal biopsies (Bx1) with systematic second biopsies (Bx2) at six months after induction therapy was studied, with a large number of light microscopic and IF variables evaluated. These were examined statistically to choose the combinations of variables with the highest overall correlations with clinical and outcome parameters. RESULTS: The adopted biopsy index comprised four elements: Glomerular Activity Index (GAI), a modification of the standard AI with the addition of glomerular monocytes and elimination of interstitial inflammation; Tubulointerstitial Activity Index (TIAI), evaluating several tubular epithelial and inflammatory components, including interstitial inflammation, but excluding tubular atrophy; Chronic Lesions Index, a modification of the standard CI, with the addition of glomerular scars; IF Index (IFI), a semiquantitative index of IF staining for six standard antisera for glomerular capillary, mesangial, tubulointerstitial, and vascular elements. The Biopsy Index showed a statistically higher correlation with clinical and outcome parameters than the NIH AI (P = 0.0170), the NIH CI (P = 0.0009), or their combination (P = 0.0444). At Bx1, comparisons between correlation coefficients for the appropriate AI or CI value and for the Biopsy Index, were: anti-DNA antibodies (0.30 vs. 045), serum creatinine (SCr; 0.33 vs. 0.48), proteinuria (0.22 vs. 0.36), hemoglobin (-0.21 vs. -0.45), and final renal function (0.22 vs. 0.40). Spearman rank correlations showed similar superiority for outcome parameters: doubling of SCr (0.1810 vs. 0.3018) and end-stage renal disease (0.0529 vs. 0.1925). The same improvement of correlations was seen at Bx2 for most parameters, particularly doubling of SCr (0.2716 vs. 0.4753). CONCLUSIONS: The Biopsy Index and/or its components show better correlations with clinical and outcome parameters than the standard AI and CI and other similar indices.