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1.
J Visc Surg ; 156(3): 229-237, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31080117

RESUMO

Retrorectal tumors (RRT), whether benign or malignant in nature, are rare in adults and often asymptomatic. While diagnosis is based on clinical findings, differential diagnosis depends mainly on magnetic resonance imaging (MRI). MRI provides guidance for surgical management, the first-line treatment of choice. Four surgical approaches are described: abdominal, perineal, posterior and abdomino-sacral.. This review of major reported series has made it possible to specify the indications for each surgical approach, as well as the advantages, disadvantages and complications of each one. The choice of surgical approach is determined by the nature of the RRT, its anatomical position relative to the middle of the third sacral vertebra (S3) and the presence or absence of invasion of the neighboring organs, the pelvis or sacral vertebrae. The abdominal route is chosen for tumors situated above the middle of S3, whether benign or malignant, but without invasion of neighboring organs. The perineal route is indicated for benign RRT situated below the middle of S3. The posterior route is chosen for tumors located below the middle of S3, and allows an associated resection of sacral segments in case of tumor invasion. The combined abdomino-sacral route is indicated for RRT above the middle of S3, when there is an invasion of a pelvic organ or a sacral vertebra. Intra- and post-operative complications are mainly hemorrhagic, neurological and infectious. The long-term prognosis is usually favorable, but varies according to the nature of the RRT and its management.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Gerenciamento Clínico , Neoplasias Retais/cirurgia , Adulto , Biópsia , Diagnóstico Diferencial , Endossonografia , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Retais/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
2.
J Robot Surg ; 13(5): 643-647, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30953270

RESUMO

The objective of this article is to present our experience with the 3-mm instruments using the Senhance surgical robotic system in gynecological and abdominal surgery from July to December 2017 by a retrospective observational study. All patients who underwent a robot-assisted 3-mm laparoscopic procedure with the Senhance surgical robotic system were enrolled. Two separate populations were involved: nine female gynecological patients and five digestive surgery patients. Five cholecystectomies, three annexectomies, four ovarian cystectomies, one myomectomy and one endometriotic nodule resection were performed. For the gynecological cases, the median time spent at the console was 37 min (12-77), while the total duration of the intervention was 81.33 min. All the interventions were performed on an outpatient basis. There were no postoperative complications. The average visual analog scale for pain (VAS) was 2.11 (± 1.91) on D0. For the abdominal surgery cases, the median time was 39 min (21-64). The average total duration of the intervention was 87.4 min (± 36.82). One of the five interventions was performed on an outpatient basis. There was one laparoscopy conversion. No postoperative complications in the 2 weeks following the operation. There are few 3-mm instruments available with the Senhance surgical robotic system, which limits the number of interventions. However, it is possible to perform gynecological interventions with 3-mm instruments on an outpatient basis in complete safety. It is possible to perform cholecystectomies by pairing the use of 3-mm and 5-mm instruments. The recent arrival of new 3-mm instruments will enable a wider range of surgical indications.


Assuntos
Doenças do Sistema Digestório/cirurgia , Doenças dos Genitais Femininos/cirurgia , Procedimentos Cirúrgicos em Ginecologia/instrumentação , Procedimentos Cirúrgicos Robóticos/instrumentação , Colecistectomia/instrumentação , Colecistectomia/métodos , Feminino , França , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Masculino , Estudos Observacionais como Assunto , Duração da Cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Segurança
3.
J Telemed Telecare ; 23(2): 292-300, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26945913

RESUMO

Introduction In this paper, we evaluated patients' perspectives on the use of a system for home tele-rehabilitation, designed for subjects with low computer literacy suffering hand impairment due to rheumatic diseases. Methods After a clinical trial assessing device effectiveness, the Psychosocial Impact of Assistive Devices Scale (PIADS), Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) and Individually Prioritised Problem Assessment (IPPA) questionnaires were administered to evaluate the system's impact on each patient's life, and the results were correlated with clinical indices. Patients were asked to continue self-administered rehabilitation with common objects. One year later, a semi-structured telephone interview gathered data on their experience. Results The system received a positive QUEST score (4.5 ± 0.3) and a modest PIADS score (0.84 ± 0.8) due to the small impact on adaptability and self-esteem. The IPPA (3.7 ± 3.4) revealed improvement in the ability to perform tasks considered important, which was significantly correlated ( r = 0.60; p < 0.02) with the clinical Health Assessment Questionnaire (HAQ) index improvement. The interviews revealed a positive engagement effect, enhanced by the need to develop skills to be able to use the device (technological challenge) and by the perception of more attention by the medical staff. This may explain the significant dropout rate (80%) from the post-trial rehabilitation of the patients who used the device. Discussion The system was largely accepted by the patients. The results suggest that the need for information on their rehabilitation progress and the technological challenge deserves further study to make patients more autonomous in cases of continuous rehabilitation.


Assuntos
Satisfação do Paciente , Doenças Reumáticas/reabilitação , Telerreabilitação/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Telerreabilitação/instrumentação
5.
J Visc Surg ; 153(6): 403-417, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27618702

RESUMO

STUDY AIM: To describe the main technical characteristics of biologic prostheses used for parietal reinforcement and to present the state of the art on their risk/benefit ratio. METHODS: We conducted a technical analysis of manufacturer specifications of the biologic prostheses that are currently available in France accompanied by a literature review by selecting meta-analyses and systematic reviews, randomized controlled trials and publications of health technology rating agencies. RESULTS: Biological implants for parietal reinforcement are mainly intended for use in a contaminated environment where the use of synthetic prostheses is contra-indicated. We identified fourteen systematic reviews and meta-analyses and one randomized controlled trial. Six ongoing clinical trials were identified as well as two clinical trials that had been interrupted. In the current state of knowledge, there are no high-level evidence data on the therapeutic contribution of biologic prostheses that allow prioritization of the various biologic prostheses according to their characteristics or their different manufacturing processes. CONCLUSION: Pending the results of current randomized controlled trials to validate the indications and an eventual specific reimbursement, indications for the use of biologic parietal reinforcement prostheses seems to be limited to rare clinical situations and only after collegial discussion.


Assuntos
Parede Abdominal/cirurgia , Bioprótese , Colágeno , Procedimentos Cirúrgicos do Sistema Digestório/instrumentação , Telas Cirúrgicas , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Humanos
6.
Eur J Surg Oncol ; 42(12): 1931-1937, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27378159

RESUMO

PURPOSES: This study assesses the value of using Intraoperative Near Infrared Fluorescence Imaging and Indocyanine green to detect colorectal carcinomatosis during oncological surgery. In colorectal carcinomatosis cancer, two of the most important prognostic factors are completeness of staging and completeness of cytoreductive surgery. Presently, intraoperative assessment of tumoral margins relies on palpation and visual inspection. The recent introduction of Near Infrared fluorescence image guidance provides new opportunities for surgical roles, particularly in cancer surgery. METHODS: The study was a non-randomized, monocentric, pilot "ex vivo" blinded clinical trial validated by the ethical committee of University Hospital of Saint Etienne. Ten patients with colorectal carcinomatosis cancer scheduled for cytoreductive surgery were included. Patients received 0.25 mg/kg of Indocyanine green intravenously 24 h before surgery. A Near Infrared camera was used to detect "ex-vivo" fluorescent lesions. RESULTS: There was no surgical mortality. Each analysis was done blindly. In a total of 88 lesions analyzed, 58 were classified by a pathologist as cancerous and 30 as non-cancerous. Among the 58 cancerous lesions, 42 were correctly classified by the Intraoperative Near-Infrared camera (sensitivity of 72.4%). Among the 30 non-cancerous lesions, 18 were correctly classified by the Intraoperative Near-Infrared camera (specificity of 60.0%). CONCLUSIONS: Near Infrared fluorescence imaging is a promising technique for intraoperative tumor identification. It could help the surgeon to determine resection margins and reduce the risk of locoregional recurrence.


Assuntos
Carcinoma/diagnóstico por imagem , Neoplasias Colorretais/patologia , Corantes , Verde de Indocianina , Imagem Óptica/métodos , Neoplasias Peritoneais/diagnóstico por imagem , Peritônio/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma/terapia , Cetuximab/uso terapêutico , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Feminino , Humanos , Hipertermia Induzida , Infusões Parenterais , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Peritoneais/terapia , Peritônio/cirurgia , Projetos Piloto
9.
Transplant Proc ; 41(4): 1378-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19460564

RESUMO

Torque Teno Virus (TTV), a nonenveloped human virus of the Circoviridae family, is hepatotropic, causing liver damage, cirrhosis, and, rarely, fulminant hepatitis. It prevails in 10% to 75% of blood donors due to environmental differences, independent of chronic hepatitis B virus (HBV)/HCV hepatitis, cryptogenic cirrhosis, alcoholic cirrhosis, and in fulminant hepatitis non-A-G. Reports about the efficacy of clinical alpha interferon are rare. In July 2007, a 65-year-old man who was serologically negative for A-E viruses presented with acute liver failure due to a ruptured hepatic artery aneurysm and underwent orthotopic liver transplantation (OLT). Immunosuppression was based on cyclosporine and steroids. At postoperative day 20, there was persistent hypertransaminasemia with otherwise normal liver function. A percutaneous hepatic biopsy documented pattern suggestive of a viral etiology. Multiple tests for hepatotropic viruses in the donor and the recipient from the pre- and post-OLT periods remained negative. Only the TTV qualitative test, assessed by polymerase chain reaction (PCR) on patient sera, was positive. Immunosuppressive therapy was not changed; no antiviral therapy was undertaken. At 6 months posttransplantation, transaminase levels spontaneously normalized and the clinical situation was unchanged. No complications were observed; the patient is in good clinical condition. No graft rejection was observed. In histologically proven non-A-E viral hepatitis, it is important to consider TTV as an incidental pathogenic agent. It may be useful to extend virological tests to TTV among transplant recipients and donors and to gain further knowledge about this virus.


Assuntos
Infecções por Vírus de DNA/complicações , Transplante de Fígado/efeitos adversos , Torque teno virus/isolamento & purificação , Idoso , Infecções por Vírus de DNA/virologia , Genes Virais , Humanos , Masculino , Reação em Cadeia da Polimerase , Torque teno virus/genética
10.
J Orthop Res ; 26(9): 1250-5, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18404656

RESUMO

Mesenchymal stem cells (MSCs) express an osteoblastic phenotype when treated with BMP-2, and BMP-2 is used clinically to induce bone formation although high doses are required. Pulsed electromagnetic fields (PEMF) also promote osteogenesis in vivo, in part through direct action on osteoblasts. We tested the hypothesis that PEMF enhances osteogenesis of MSCs in the presence of an inductive stimulus like BMP-2. Confluent cultures of human MSCs were grown on calcium phosphate disks and were treated with osteogenic media (OM), OM containing 40 ng/mL rhBMP-2, OM + PEMF (8 h/day), or OM + BMP-2 + PEMF. MSCs demonstrated minor increases in alkaline phosphatase (ALP) during 24 days in culture and no change in osteocalcin. OM increased ALP and osteocalcin by day 6, but PEMF had no additional effect at any time. BMP-2 was stimulatory over OM, and PEMF + BMP-2 synergistically increased ALP and osteocalcin. PEMF also enhanced the effects of BMP-2 on PGE2, latent and active TGF-beta1, and osteoprotegerin. Effects of PEMF on BMP-2-treated cells were greatest at days 12 to 20. These results demonstrate that PEMF enhances osteogenic effects of BMP-2 on MSCs cultured on calcium phosphate substrates, suggesting that PEMF will improve MSC response to BMP-2 in vivo in a bone environment.


Assuntos
Proteínas Morfogenéticas Ósseas/farmacologia , Campos Eletromagnéticos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Fosfatase Alcalina/metabolismo , Proteína Morfogenética Óssea 2 , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Dinoprostona/metabolismo , Sinergismo Farmacológico , Humanos , Osteocalcina/metabolismo , Osteogênese/fisiologia , Osteoprotegerina/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
11.
Ann Ital Chir ; 75(6): 635-41; discussion 641-2, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15960357

RESUMO

PURPOSE: We describe our experience in the multimodal treatment of HCC patients both using the PRFTA and IRFTA treatment associated or not with hepatic resection, valuating the feasibility, the complication, length of hospital stay and survival rate of selected HCC patients. MATERIALS AND METHODS: Between March 1998 and January 2004, 53 HCC patients undergoing PRFTA and IRFTA treatment. We describe 41 patients with monofocal disease and 12 patients with multifocal disease: in this last group 7 patients had unilobar involvement while 5 patients had multilobar tumour. RESULTS: We reported patients underwent RFTA because not candidates to surgical procedures and patients underwent liver resection and open radiofrequency treatment associated. We successfully used percutaneous and intraoperative approach being the last one significantly advantageous in lesions greater than 5 cm, multiple bilobar tumours and tumours close to the hilum and major vessels: the laparotomic approach permitted the temporary occlusion of the vascular inflow allowing Pringle manoeuvre. DISCUSSION: Hepatocarcinoma still represent one of the major causes of cancer related death worldwide. Systemic therapeutic agents and locoregional agents are rarely correlated to complete response and usually associated to high toxicities: the potentially curative or palliative benefit of RFTA in non surgical candidates improve overall patients survival significally better then the chemotherapy regimens. CONCLUSION: RFTA appears to have several advantages, which also include a reducing in morbidity, a shortening of the hospital stay and good response to patients requirement in term of enduring pain.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Neoplasias Hepáticas/cirurgia , Ablação por Cateter/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
12.
J Clin Apher ; 16(1): 37-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11309832

RESUMO

Vascular involvement is presently considered a "common pathway" in a number of diseases that is mediated by circulating immune complexes (CIC). CIC are found in the circulation when the disease is active and in single patients their level may parallel disease activity. Lepromatous leprosis is characterized by the presence of CIC and deposits of immunoglobulins and complement in vascular lesions of the different organs and an Arthus-like mechanism is considered as the basis for the clinical picture. The same mechanism is considered to play an essential pathophysiologic role in Lucio's phenomenon, which is characterized by lymphohistiocytic vascular infiltrates with or without thrombosis and secondary cutaneous infarction. Lepromatous vascular involvement is mediated by CIC whose antigen composition is known, the same as it is with HCV mediated cryoglobulinemia, HBV positive panarteritis nodosa, rheumatoid vasculitis, or Wagner's granulomatosis, which are usually treated by PE [1-3]. PE has been employed for lepromatous vasculitis since 1979 [4] and other cases have been successfully treated afterwards [5,6]. We report on another patient successfully treated by plasma exchange.


Assuntos
Hanseníase Virchowiana/complicações , Hanseníase Virchowiana/terapia , Troca Plasmática , Vasculite/etiologia , Vasculite/terapia , Humanos , Hanseníase Virchowiana/imunologia , Pessoa de Meia-Idade , Vasculite/imunologia
13.
14.
Blood ; 95(4): 1293-300, 2000 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-10666202

RESUMO

Phospholipid asymmetry is well maintained in erythrocyte (RBC) membranes with phosphatidylserine (PS) exclusively present in the inner leaflet. The appearance of PS on the surface of the cell can have major physiologic consequences, including increased cell-cell interactions. Because increased adherence of PS-exposing RBCs to endothelial cells (ECs) may be pathologically important in hemoglobinopathies such as sickle cell disease and thalassemia, we studied the role of PS exposure in calcium ionophore-treated normal RBC adherence to human umbilical vein endothelial cell (HUVEC) monolayers. When HUVEC monolayers were incubated with these PS-exposing RBCs, the ECs retracted and the RBCs adhered primarily in the gaps opened between the ECs. A linear correlation was found between the number of PS-exposing RBCs in the population and the number of adhering RBCs to the monolayer. Pretreatment of RBCs with annexin V significantly decreased adherence by shielding PS on the RBCs. Similarly, PS-containing lipid vesicles decreased RBC binding by competing for the PS binding sites in the monolayer. PS-exposing RBCs and PS-containing lipid vesicles adhered to immobilized thrombospondin (TSP) and matrix TSP, respectively, and adherence of PS-exposing RBCs to EC monolayers was reduced by antibodies to TSP and to its EC receptor, alpha(v)beta(3). Together, these results indicate a role for PS and matrix TSP in the adherence of PS-exposing RBCs to EC monolayers, and suggest an important contribution of PS-exposing RBCs in pathologies with reported vascular damage, such as sickle cell anemia. (Blood. 2000;95:1293-1300)


Assuntos
Anemia Falciforme/sangue , Adesão Celular/fisiologia , Endotélio Vascular/fisiologia , Eritrócitos/fisiologia , Fosfatidilserinas/farmacologia , Trombospondinas/fisiologia , Proteína 1 de Troca de Ânion do Eritrócito/fisiologia , Antígenos CD/sangue , Antígenos CD36/sangue , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Criança , Endotélio Vascular/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Matriz Extracelular/fisiologia , Histamina/farmacologia , Humanos , Técnicas In Vitro , Valores de Referência , Veias Umbilicais
15.
Proc Natl Acad Sci U S A ; 96(5): 2350-5, 1999 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-10051645

RESUMO

Efficient and safe heparin anticoagulation has remained a problem for continuous renal replacement therapies and intermittent hemodialysis for patients with acute renal failure. To make heparin therapy safer for the patient with acute renal failure at high risk of bleeding, we have proposed regional heparinization of the circuit via an immobilized heparinase I filter. This study tested a device based on Taylor-Couette flow and simultaneous separation/reaction for efficacy and safety of heparin removal in a sheep model. Heparinase I was immobilized onto agarose beads via cyanogen bromide activation. The device, referred to as a vortex flow plasmapheretic reactor, consisted of two concentric cylinders, a priming volume of 45 ml, a microporous membrane for plasma separation, and an outer compartment where the immobilized heparinase I was fluidized separately from the blood cells. Manual white cell and platelet counts, hematocrit, total protein, and fibrinogen assays were performed. Heparin levels were indirectly measured via whole-blood recalcification times (WBRTs). The vortex flow plasmapheretic reactor maintained significantly higher heparin levels in the extracorporeal circuit than in the sheep (device inlet WBRTs were 1. 5 times the device outlet WBRTs) with no hemolysis. The reactor treatment did not effect any physiologically significant changes in complete blood cell counts, platelets, and protein levels for up to 2 hr of operation. Furthermore, gross necropsy and histopathology did not show any significant abnormalities in the kidney, liver, heart, brain, and spleen.


Assuntos
Enzimas Imobilizadas , Heparina Liase , Heparina/efeitos adversos , Plasmaferese/instrumentação , Injúria Renal Aguda/terapia , Animais , Anticoagulantes/efeitos adversos , Desenho de Equipamento , Heparina/metabolismo , Humanos , Plasmaferese/métodos , Diálise Renal , Terapia de Substituição Renal , Ovinos
16.
Blood ; 93(4): 1422-9, 1999 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-9949187

RESUMO

The abnormal adherence of sickle red blood cells (SS RBC) to vascular endothelium may play an important role in vasoocclusion in sickle cell anemia. Thrombospondin (TSP), unusually large molecular weight forms of von Willebrand factor, and laminin are known to enhance adhesion of SS RBC. Also, these endothelial proteins bind to sulfated glycolipids and this binding is inhibited by anionic polysaccharides. Reversible sickling may expose normally cryptic membrane sulfatides that could mediate this adhesive interaction. In this study, we have investigated the effect of anionic polysaccharides, in the presence or absence of TSP, on SS RBC adhesion to the endothelium, using cultured human umbilical vein endothelial cells (HUVEC) (for the adhesion assay) and the ex vivo mesocecum of the rat (for hemodynamic evaluation). The baseline adhesion (ie, without added TSP) of SS RBC to HUVEC was most effectively inhibited by high molecular weight dextran sulfate (HDS), whereas low molecular weight dextran sulfate (LDS) and the glycosaminoglycan chondroitin sulfate A (CSA) also had significant inhibitory effects. Heparin was mildly effective whereas other glycosaminoglycans (chondroitin sulfates B and C, heparan sulfate, and fucoidan) were ineffective. Similarly, HDS and CSA resulted in an improved hemodynamic behavior of SS RBC. Soluble TSP caused significant increases in SS RBC adhesion and in the peripheral resistance. Both HDS and CSA prevented TSP-enhanced adhesion and hemodynamic abnormalities. Thus, anionic polysaccharides can inhibit SS RBC-endothelium interaction in the presence or absence of soluble TSP. These agents may interact with RBC membrane component(s) and prevent TSP-mediated adhesion of SS RBC to the endothelium.


Assuntos
Anemia Falciforme/patologia , Endotélio Vascular/patologia , Eritrócitos/patologia , Hemodinâmica/efeitos dos fármacos , Polissacarídeos/farmacologia , Trombospondinas/farmacologia , Adulto , Anemia Falciforme/sangue , Animais , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Ratos
17.
Arch Ital Urol Androl ; 71(5): 287-92, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10673792

RESUMO

An investigative trial including 72 patients who underwent open surgery for benign prostatic hypertrophy (BPH) induced urinary symptoms was carried out with the purpose to obtain a deeper insight in the pathophysiology of this clinical picture. Prostate weight, stroma to parenchyma ratio, bladder wall fibrosis, I-PSS score, residual urine and uroflow obtained from these patients were processed by statistical multivariate analysis. The results point out the pivotal impact of prostate and bladder wall fibrosis in conditioning biological and chronological ageing of the lower urinary tract and relative symptoms.


Assuntos
Próstata/patologia , Próstata/fisiopatologia , Hiperplasia Prostática/patologia , Hiperplasia Prostática/fisiopatologia , Bexiga Urinária/patologia , Bexiga Urinária/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Urodinâmica
18.
Blood ; 89(7): 2560-7, 1997 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-9116303

RESUMO

Sickle red blood cell (RBC) adhesion to the blood vessel wall is hypothesized to be the initiating event in the periodic vaso-occlusive episodes that characterize sickle cell disease (SCD). Thrombospondin-1 (TSP) and von Willebrand factor (vWF) have each been implicated in the adhesion of sickle RBC to vascular endothelial cells (EC) and subendothelial matrices. To better understand the contributions of each of these adhesive glycoproteins, we examined the adhesion of sickle RBC to immobilized TSP and vWF using a parallel plate flow chamber. Under postcapillary venular shear stress (1 dyne/cm2), sickle RBC adhered preferentially to TSP. To explore potential interactive effects of vWF and TSP, we examined sickle RBC adhesion to mixtures of these proteins. Whether the proteins were first combined in solution or sequentially applied to the slide, the presence of vWF inhibited the binding of sickle RBC to TSP. The inhibition of adhesion by vWF was shown to be the result of specific and saturable binding of vWF to TSP. Furthermore, vWF in solution at normal plasma levels also inhibited RBC adhesion to immobilized TSP. These data indicate that sickle RBC adhesion in vivo may be significantly influenced by the relative concentrations of TSP and vWF in the vascular wall.


Assuntos
Anemia Falciforme/patologia , Glicoproteínas de Membrana/metabolismo , Fator de von Willebrand/farmacologia , Anemia Falciforme/sangue , Adesão Celular/efeitos dos fármacos , Endotélio Vascular/patologia , Hemorreologia , Humanos , Ligação Proteica/efeitos dos fármacos , Estresse Mecânico , Trombospondinas
19.
Blood ; 88(12): 4701-10, 1996 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-8977264

RESUMO

During 24 weeks of hydroxyurea treatment, we monitored red blood cell (RBC) parameters in three patients with sickle cell disease, including F-cell and F-reticulocyte profiles, distributions of delay times for intracellular polymerization, sickle erythrocyte adherence to human umbilical vein endothelial cells in a laminar flow chamber, RBC phthalate density profiles, mean corpuscular hemoglobin concentration and cation content, reticulocyte mean corpuscular hemoglobin concentration, 1H-nuclear magnetic resonance transverse relaxation rates of packed RBCs, and plasma membrane lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea increases the fraction of cells with sufficiently long delay times to escape the microcirculation before polymerization begins. Furthermore, high pretreatment adherence to human umbilical vein endothelial cells of sickle RBCs decreased to normal after only 2 weeks of hydroxyurea treatment, preceding the increase in fetal hemoglobin levels. The lower adhesion of sickle RBCs to endothelium would facilitate escape from the microcirculation before polymerization begins. Hydroxyurea shifted several biochemical and biophysical parameters of sickle erythrocytes toward values observed with hemoglobin SC disease, suggesting that hydroxyurea moderates sickle cell disease toward the milder, but still clinically significant, hemoglobin SC disease. The 50% reduction in sickle crises documented in the Multicenter Study of Hydroxyurea in Sickle Cell Disease is consistent with this degree of erythrocyte improvement.


Assuntos
Eritrócitos/efeitos dos fármacos , Doença da Hemoglobina SC/sangue , Doença da Hemoglobina SC/tratamento farmacológico , Hidroxiureia/uso terapêutico , Adulto , Proteína 1 de Troca de Ânion do Eritrócito/fisiologia , Adesão Celular/efeitos dos fármacos , Cloretos/metabolismo , Endotélio Vascular/citologia , Agregação Eritrocítica/tratamento farmacológico , Eritrócitos/química , Eritrócitos/citologia , Feminino , Hemoglobina Fetal/análise , Humanos , Transporte de Íons/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Masculino , Potássio/metabolismo
20.
Blood ; 87(2): 771-80, 1996 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-8555502

RESUMO

The pathophysiology of vaso-occlusive crisis in sickle cell disease involves interactions among blood cells, plasma proteins, and vessel wall components. The initial goal of this work was to quantify the adhesion of sickle red blood cells (RBCs) to fibronectin immobilized on glass under both static and dynamic shear stress conditions. High-power microscopic inspection of static assay plates showed striking numbers of adherent neutrophils as well as RBCs. Sickle neutrophils and RBCs were significantly more adherent to fibronectin than the corresponding normal cells in static adhesion assays. Adhesion of both sickle neutrophils and sickle RBCs in dynamic adhesion assays was promoted by a period of static incubation preceding initiation of shear stress conditions. Adherent neutrophils remained attached at shear stresses up to 51 dyne/cm2; most adherent RBCs were attached at shear stresses up to 13 dyne/cm2, but detached at a shear stress of 20 dyne/cm2. Sickle neutrophil adhesion was enhanced significantly by autologous plasma. Elevated levels of plasma interleukin-6 (IL-6; but not IL-1 or IL-8) were found in 6 of 9 sickle cell disease samples examined, and elevated levels of tumor necrosis factor were found in 2 of 9 samples. Plasma IL-6 levels correlated positively with both the number of sickle neutrophils adherent to fibronectin and the ability of sickle plasma to enhance adhesion of normal neutrophils to fibronectin. These data suggest possible roles for neutrophil activation and for fibronectin in mediating sickle neutrophil and RBC adhesion.


Assuntos
Eritrócitos Anormais/fisiologia , Fibronectinas/metabolismo , Neutrófilos/fisiologia , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/fisiopatologia , Adesão Celular , Vidro , Hemorreologia , Humanos , Interleucina-6/sangue , Microcirculação , Plasma , Estresse Mecânico
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