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The clinical and pathological presentation of thyroid nodules among younger and adult patients was compared in an iodine-deficient (ID) region. Data of 3,010 consecutive patients younger than 20 years and 3,010 patients older than 20 years were compared. The proportion of nodular goiters (22.8% versus 39.3%), the ratio of surgically treated nodules (33.2% versus 15.2%), and the proportion of malignant nodules (4.3% versus 2.1%) among diseased patients differed significantly between the two groups (younger versus adult). Nine papillary and 1 medullary carcinoma were found among children, while 15 papillary, 2 follicular, 1 insular, 1 anaplastic, and 1 medullary carcinomas occurred among adults. The ratio of follicular adenoma to hyperplastic nodules (3 : 1 to 1 : 1.67), the proportion of follicular variant (77.8% versus 26.7%), T4 tumors (77.8% versus 33.3%), and tumors with lymph node metastasis (88.9% versus 66.7%) were significantly higher among younger papillary carcinoma patients. No malignancies occurred among spongiform and central type cysts. Similarly to iodine-sufficient regions, more nodules are malignant and carcinomas have a clinically more aggressive presentation in children in comparison with adult patients in ID. Taking the significantly greater proportion of adenomas and the lack of follicular carcinoma into account, a conservative approach has to be considered in follicular tumors among children.
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BACKGROUND: The appropriate surgical procedure for benign multinodular goiters is debated. We report our clinical experience of performing total thyroidectomy for multinodular goiters, focusing on the outcome and complications to evaluate the efficacy and safety. MATERIAL AND METHODS: The medical records of 264 patients who underwent total thyroidectomy for multinodular goiter between 2000 and 2006 were reviewed retrospectively. We examined the indications for operation, average hospital stay, early and late postoperative complications, the results of the final pathology in particular the frequency of incidental thyroid cancers and the recurrence rates after an average 6.2 years follow-up. The results were compared to literature data. RESULTS: The indications for surgery were compression and/or dislocation of the trachea in 174 (65.9%) patients, hyperthyreodism in 74 (28%) and cosmetic problems in others. The mean hospital stay was 4 days. Thirty-one patients (11.7%) had transient hypocalcaemia, but only 1 (0.3%) was symptomatic, and only 4 (1.5%) had permanent hypocalcaemia. Other complications included hematoma 4 (1.5%), temporary unilateral recurrent laryngeal nerve palsy 7 (2.6%), permanent unilateral laryngeal nerve palsy 2 (0.75%), and seroma in 8 (3%) cases. Incidental thyroid carcinomas were found on hystology in 9 (3.5%) patients. No recurrence was observed during the follow-up. CONCLUSION: Total thyroidectomy may be the procedure of choice for the surgical management of benign multinodular goiter.
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Bocio Nodular/cirugía , Hallazgos Incidentales , Neoplasias de la Tiroides/cirugía , Tiroidectomía/efectos adversos , Tiroidectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Constricción Patológica/etiología , Constricción Patológica/cirugía , Femenino , Bocio Nodular/complicaciones , Humanos , Hipertiroidismo/etiología , Hipertiroidismo/cirugía , Hipocalcemia/etiología , Tiempo de Internación , Masculino , Registros Médicos , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Seguridad , Seroma/etiología , Neoplasias de la Tiroides/complicaciones , Factores de Tiempo , Tráquea/patología , Resultado del Tratamiento , Parálisis de los Pliegues Vocales/etiologíaRESUMEN
Background. There is a current debate in the medical literature about plasma calcitonin screening in patients with nodular goiter (NG). We decided on analyzing our 20-year experience with patients in an iodine-deficient region (ID). Patients and Methods. 22,857 consecutive patients with NG underwent ultrasonography and aspiration cytology (FNAC). If FNAC raised suspicion of medullary cancer (MTC), the serum calcitonin was measured. Results. 4,601 patients underwent surgery; there were 23 patients among them who had MTC (0.1% prevalence). Significantly more MTC cases were diagnosed cytologically in the second decade than in the first: 11/12 and 6/11, respectively. The frozen section was of help in 2 cases out of 3. Two patients suffered from a 3-year delay in proper therapy, and reoperation was necessary in 1 case. FNAC raised the suspicion of MTC in 20 cases that were later histologically verified and did not present MTC. The diagnostic accuracy of FNAC in diagnosing MTC was 99.2%. Two false-positive serum calcitonin tests (one of them in a hemodialyzed patient) and one false-negative serum calcitonin test occurred in 40 cases. Conclusion. Regarding the low prevalence of MTC in ID regions, calcitonin screening of all NG patients does not only appear superfluously but may have more disadvantages than advantages.
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INTRODUCTION: The Natural Orifice Transluminal Endoscopic Surgery (NOTES) is the newest trend in minimally invasive surgery. Based on clinical experiences, transvaginal cholecystectomy causes less pain and operative stress, requires shorter hospitalization and allows patients to return quicker to normal activity. MATERIALS AND METHODS: A transvaginal cholecystectomy was carried out using hybrid technique in animal model first time in Hungary. A 5 mm umbilical trocar was used for preparation of cystic artery and duct, clip application and gallbladder dissection. A transvaginally inserted 10 mm trocar was used for laparoscopic camera to follow the procedure. Gallbladder was fixed and secured with a special curved instrument inserted also transvaginally during the procedure. At the end of procedure the gallbladder was removed transvaginally. RESULTS: Six transvaginal cholecystectomies was performed on pigs. The mean time of operations was 78 min (40-145 minutes). During the operations and the follow up period (3 months) no complications and mortality was detected. CONCLUSIONS: According to our experiences both procedures can be safely carried out on animal model, but further refinement of devices is necessary.
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Colecistectomía Laparoscópica/métodos , Endoscopía/métodos , Vagina , Animales , Colecistectomía Laparoscópica/efectos adversos , Endoscopía/efectos adversos , Femenino , Hungría , Modelos Animales , Sus scrofaRESUMEN
CD44, the leukocyte adhesion receptor for hyaluronan, has been considered a therapeutic target on the basis of the robust anti-inflammatory effect of CD44-specific antibodies in animal models of immune-mediated diseases. However, CD44 deficiency does not provide substantial protection against inflammation. Using intravital video microscopy in a murine model of rheumatoid arthritis, we show that CD44 deficiency and anti-CD44 antibody treatment exert disparate effects on leukocyte recruitment in inflamed joints. Leukocyte rolling, which is increased in CD44-deficient mice, is promptly abrogated in anti-CD44-treated wild-type mice. CD44-specific antibodies also trigger platelet deposition on granulocytes and subsequent depletion of this leukocyte subset in the circulation. These in vivo effects require CD44 cross-linking and are reproducible with an antibody against Gr-1, a molecule that, like CD44, is highly expressed on granulocytes. Anticoagulant pretreatment, which prevents platelet deposition, mitigates both granulocyte depletion and the suppressive effect of CD44-specific antibody on joint swelling. Our observations suggest that cross-linking of prominent cell surface molecules, such as CD44 or Gr-1, can initiate a rapid self-elimination program in granulocytes through engagement of the coagulation system. We conclude that the robust anti-inflammatory effect of CD44-specific antibodies in arthritis is primarily the result of their ability to trigger granulocyte depletion.
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Anticuerpos Monoclonales/farmacología , Artritis/tratamiento farmacológico , Quimiotaxis de Leucocito/efectos de los fármacos , Granulocitos/efectos de los fármacos , Receptores de Hialuranos/inmunología , Rodamiento de Leucocito/efectos de los fármacos , Receptores de Quimiocina/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Artritis/patología , Plaquetas , Adhesión Celular , Modelos Animales de Enfermedad , Femenino , Inflamación/tratamiento farmacológico , Leucocitos , Ratones , Ratones Endogámicos BALB CRESUMEN
Rheumatoid arthritis, in common with other systemic autoimmune diseases, can involve several other organs presenting with complex immunological manifestations. Immune thrombocytopenic purpura caused by an autoimmune reaction against platelets is an infrequent haematological complications. A female patient with rheumatoid arthritis rapidly developed extremely severe immune thrombocytopenic purpura upon suspending oral corticosteroid therapy. Besides the involvement of the mucosa of the coecum, ascending colon and the gastric antrum, the situation was further complicated by bleeding of a gastric polyp, at the nadir of the thrombocytopenic crisis. The bleeding was managed by endoscopic intervention and platelet count recovered upon high dose corticosteroid treatment within a couple of days.
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Artritis Reumatoide/complicaciones , Hemorragia Gastrointestinal/etiología , Púrpura Trombocitopénica Idiopática/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Femenino , Hemorragia Gastrointestinal/terapia , Humanos , Persona de Mediana Edad , Pólipos/complicaciones , Gastropatías/complicacionesRESUMEN
BACKGROUND: Since the first description of the minimally invasive totally gasless video-assisted thyroidectomy (MIVAT) technique in 1998, relatively few studies have evaluated the outcome of this procedure. The authors review their experiences based on a prospective randomized trial comparing the potential advantages of MIVAT over conventional thyroidectomy. METHODS: Patients undergoing surgery for either thyroid nodule or diffuse thyroid disease with hyperthyroidism were randomly selected for either MIVAT or conventional thyroidectomy. The exclusion criteria specified nodules larger than 35 mm, thyroid lobe volume greater than 20 ml, thyroiditis, and previous neck irradiation or surgery. Operative time, postoperative complications, and cosmetic results were evaluated using both a verbal response scale and a numeric scale. RESULTS: Both the MIVAT group and the conventional thyroidectomy group included 15 patients. No significant differences were noted between the two groups in terms of age, sex, or indication for operation. The mean operative times were 65.5 +/- 18 min. for MIVAT and 43.3 +/- 14 min. for conventional thyroidectomy (P = 0.001). No postoperative complications were detected in either group. The cosmetic results, evaluated by both verbal response and numeric scales, were respectively as follows: MIVAT (3.7 +/- 0.2 and 7.9 +/- 1.2) and conventional thyroidectomy (2.3 +/- 0.7 and 4.9 +/- 1.3). The differences significantly favored MIVAT (P = 0.028 and P = 0.015, respectively) despite the small number of patients enrolled in this study, and consequently, its limited statistical power. CONCLUSION: Although the complications are comparable between the two approaches, conventional thyroidectomy involves less operative time. However, MIVAT offers distinct advantages to selected patients in terms of very good to exellent cosmetic results and reduced postoperative distress.
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Hipertiroidismo/cirugía , Tiroidectomía/métodos , Cirugía Asistida por Video/métodos , Adulto , Anciano , Estética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Complicaciones Posoperatorias , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Stromal tumors of the gastrointestinal tract are rare mesenchymal neoplasms. The majority of them are appearing in the stomach: their quite common first manifestation is bleeding. The authors report a case of polypoid gastric GIST causing severe bleeding which needed urgent surgical intervention and partial resection of the stomach. Although histological analysis of the tumor revealed low proliferation rate, the urgent operation did not result in a complete eradication of the neoplasm, thereby our patient needs further follow-up and treatment.
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Hemorragia Gastrointestinal/etiología , Tumores del Estroma Gastrointestinal/complicaciones , Neoplasias Gástricas/complicaciones , Anciano , Proliferación Celular , Úlcera Duodenal/complicaciones , Femenino , Gastrectomía/métodos , Arteria Gastroepiploica , Tumores del Estroma Gastrointestinal/patología , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugíaRESUMEN
OBJECTIVES: The use of self-expandable plastic stents has offered a reasonable alternative of self-expandable metal stents in palliative treatment of esophageal malignancies, in the recent years. Studies and clinical data on the use of self-expandable plastic stents in esophageal cancer are, however, available in a very limited number. Here, we present the results of our 3-year study designed to evaluate the efficacy of self-expandable plastic stents in palliation of advanced esophageal carcinoma. PATIENTS AND METHODS: Between January 2001 and February 2004, 69 patients with advanced nonoperable esophageal cancer were enrolled in the study and followed up until their death, after insertion of Polyflex self-expandable plastic stents. Dysphagia scores, Karnofsky indices and body weights were determined and compared in order to evaluate the effect of the stent insertion on general status and well-being of the patients. RESULTS: Insertion of Polyflex self-expandable plastic stents and covered self-expandable metal stents was performed in 66 cases and in eight cases, respectively; in certain patients, owing to complications, more than one stent had to be inserted. In all cases, the insertion of stents has been performed without major complication and it has led to an instant improvement in swallowing and dysphagia scores. The rates of tumoral overgrowth and of stent migration were low. The mean follow-up time of our patients was 129 days (10-312 days). CONCLUSION: In concordance with previous studies, according to our results, the use of self-expandable plastic stents in palliation of esophageal cancer seems to be safe and effective in improving the quality of life of these patients.
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Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Cuidados Paliativos/métodos , Stents , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Cateterismo , Trastornos de Deglución/terapia , Diseño de Equipo , Neoplasias Esofágicas/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: This study was undertaken to investigate how fibroblasts respond to stimulation with particulate wear debris and/or conditioned media obtained from pathologic tissue, and whether these activated fibroblasts express compounds that are involved in bone resorption. METHODS: Conditioned media from explant cultures of synovial tissue, periprosthetic soft tissue (interface membranes), titanium particles, and proinflammatory cytokines were used to stimulate fibroblasts. RNase protection assay was used to measure altered gene expression, and enzyme-linked immunosorbent assay, Western blot hybridization, and flow cytometry were used to determine fibroblast protein expression. Tartrate-resistant acid phosphatase staining was used to identify multinucleated osteoclast-like cells. RESULTS: The most dominant compounds measured in the conditioned media from interface membranes were tumor necrosis factor alpha (TNFalpha), monocyte chemoattractant protein 1 (MCP-1), interleukin-1beta (IL-1beta), IL-6, IL-8, and vascular endothelial growth factor. Fibroblasts phagocytosed particulate wear debris and responded to cytokine/chemokine stimulation. The most prominent up-regulated genes and proteins secreted by fibroblasts in response to stimulation were matrix metalloproteinase 1, MCP-1, IL-1beta, IL-6, IL-8, cyclooxygenase 1 (COX-1), COX-2, leukemia inhibitory factor 1, transforming growth factor beta1 (TGFbeta1), and TGFbeta receptor type I. In addition, interface membrane fibroblasts expressed RANKL and osteoprotegerin in response to stimulation with conditioned media, TNFalpha, or IL-1beta. Stimulated fibroblasts cocultured with bone marrow cells in the presence of macrophage colony-stimulating factor induced osteoclastogenesis. CONCLUSION: Interface membrane fibroblasts respond directly to particulate wear debris, possibly via phagocytosis, expressing proinflammatory cytokines and RANKL. Thus, these cells may be actively involved in osteoclastogenesis and pathologic (periprosthetic) bone resorption.
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Artroplastia de Reemplazo de Rodilla/efectos adversos , Citocinas/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Prótesis de la Rodilla/efectos adversos , Osteólisis/etiología , Osteólisis/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Resorción Ósea/genética , Resorción Ósea/metabolismo , Resorción Ósea/patología , Resorción Ósea/fisiopatología , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Citocinas/genética , Femenino , Fibroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Humanos , Factor Estimulante de Colonias de Macrófagos/genética , Factor Estimulante de Colonias de Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Osteoclastos/efectos de los fármacos , Osteoclastos/patología , Osteólisis/patología , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Fagocitosis , Ligando RANK/genética , Ligando RANK/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Titanio/farmacología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The pathogenesis of inflammatory bowel disease (IBD) is only partially understood. Various environmental and host (e.g. genetic-, epithelial-, immune and non-immune) factors are involved. It is a multifactorial polygenic disease with probable genetic heterogeneity. Some genes are associated with IBD itself, while others increase the risk of ulcerative colitis (UC) or Crohn's disease (CD) or are associated with disease location and/or behaviour. This review addresses recent advances in the genetics of IBD. The article discusses the current information on the crosstalk between microbial and genetic factors (e.g. NOD2/CARD15, SLC22A46A5 and DLG5). The genetic data acquired in recent years help in understanding the pathogenesis of IBD and can identify a number of potential targets for therapeutic intervention. In the future, genetics may help more accurately diagnose and predict disease course in IBD.
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Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/microbiología , Mucosa Intestinal/fisiopatología , Receptores Toll-Like/fisiología , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/fisiología , Clostridioides difficile/fisiología , Citocinas/genética , Citocinas/fisiología , Escherichia coli/fisiología , Regulación de la Expresión Génica , Antígenos HLA/genética , Antígenos HLA/fisiología , Humanos , Enfermedades Inflamatorias del Intestino/fisiopatología , Mucosa Intestinal/microbiología , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/fisiología , Lactobacillus/fisiología , Receptores de Lipopolisacáridos/genética , Receptores de Lipopolisacáridos/fisiología , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Mycobacterium avium subsp. paratuberculosis/fisiología , Proteína Adaptadora de Señalización NOD1 , Proteína Adaptadora de Señalización NOD2 , Proteínas de Transporte de Catión Orgánico/genética , Proteínas de Transporte de Catión Orgánico/fisiología , Receptor Cross-Talk , Miembro 5 de la Familia 22 de Transportadores de Solutos , Simportadores , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/fisiología , Receptores Toll-Like/genética , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/fisiologíaRESUMEN
Minimally invasive video-assisted thyroidectomy (MIVAT) was published in 1998. In this paper authors describe their initial experiences with this new technique, which is the first publication in their country on this topic based on authors knowledge. Ten patients were selected for MIVAT. Selection criteria were nodule size less than 30 mm, thyroid lobe volume less than 20 ml, no thyroiditis, no previous neck surgery or irradiation. The procedure was carried out through a 20-25 mm central incision above the sternal notch. Dissection was performed under endoscopic vision, using endoscopic, some special and conventional instruments. Authors performed 1 total thyroidectomy, 6 lobectomies, 2 lobectomies with subtotal resection on the opposite side, and 1 resection of thyroid isthmus. Mean operative time was 77 minutes. No conversion to open procedure was performed. No recurrent laryngeal nerve palsy or postoperative hypocalcemia were observed postoperatively. The mean hospital stay was 2 days. The cosmetic result and the postoperative distress were considered very good by the patients. The authors conclude that MIVAT is a safe and feasible procedure. The indications are limited, but in this small group of patients offer excellent cosmetic results with less postoperative distress.
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Tiroidectomía/métodos , Cirugía Asistida por Video/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estudios Retrospectivos , Tiroidectomía/efectos adversosRESUMEN
AIMS: The stricture of the anastomosis is one of the most common complications of the subtotal esophageal resections. The authors present indications, technics and results of the endoscopic dilatation. PATIENTS AND METHODS: In a 10 year period 26 patients (22 male, 4 female, mean age of 53.7 years) with stricture of anastomosis between the esophagus and the neo-esophagus after subtotal esophageal resection were dilated endoscopically 82 times. The indication of the resection was tumour in 23 (88.5%) cases, congenital atresia in 2 (7.7%) cases and corrosive disease in one (3.8%) case. In 7 (31.8%) cases the stricture developed after anastomosis leakage. The mean time between the operation and the dilatation was 7.8 months. The cause of the stricture was cancer recurrency in 4 (15.4%) cases. RESULTS: There were no complications related to the dilatation. The mean number of the dilatation was 3.2 (1-9). There was no significant difference between the number of dilatation in patients with or without previously anastomotic leakage. The success rate of the dilatation for benign strictures was 95.5%. In only one patient (4.5%) was needed operative intervention. In the 4 patients with tumour recurrency a stent was also implanted in the stenosis. CONCLUSIONS: The endoscopic dilatation for the treatment of the cervical anastomosis stricture after subtotal esophageal resection is a successful method with a low rate of complications. In cases of tumour recurrency a stent implantation is suggested.
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Cateterismo , Esofagectomía/efectos adversos , Adolescente , Adulto , Anciano , Anastomosis Quirúrgica/efectos adversos , Niño , Preescolar , Constricción Patológica/etiología , Constricción Patológica/terapia , Esofagectomía/métodos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Of patients with malignant esophageal tumors, more than the half has incurable disease at the time of diagnosis. In such cases, quality of life and ability to swallow should be improved or restored by palliating the process e.g. by inserting esophageal stents. In the recent years, use of covered self-expandable metal stents (SEMS) has led to an increased success rate in the palliative treatment of--mainly malignant--strictures of the esophagus. High occurrence of complications (perforation, bleeding) associated with the use of rigid plastic esophageal stents necessitated the development of flexible stents. First generation self-expandable stents were made of special metal alloys, such as nickel-titanium. In the recent years, self-expandable plastic stents are available, too, offering new alternatives in the palliative treatment of esophageal diseases. In our present review article, we discuss the most important aspects about the use of self-expanding esophageal stents, based on recent clinical observations and data.
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Enfermedades del Esófago/cirugía , Stents , Animales , Deglución , Enfermedades del Esófago/fisiopatología , Neoplasias Esofágicas/cirugía , Humanos , Diseño de Prótesis , Calidad de Vida , Stents/efectos adversosRESUMEN
INTRODUCTION: Since its recent introduction, capsule endoscopy has revolutionized the diagnostics of diseases of the small bowel. The number of studies on the use of this method is constantly increasing. Along with this, our knowledge about the usability and diagnostic power of capsule endoscopy is growing and the indications for this technique are getting progressively more accurate. AIMS: To study the usability of capsule endoscopy in suspected Crohn's disease, in gastrointestinal bleeding of small bowel origin, and in undetermined abdominal complains. METHOD: Capsule endoscopy was performed in 20, previously examined, carefully selected patients. RESULTS: Positive findings were recorded in all patients with gastrointestinal bleeding and in 3/4 of patients with suspected Crohn's disease. However, in patients with indeterminate abdominal complains, the capsule endoscopy proved to be inefficient. CONCLUSION: In the study below, based on their own experience, the authors try to provide an overall picture of capsule endoscopy by reviewing contemporary medical literature. The usability of the capsule endoscopy in suspected Crohn's disease and gastrointestinal bleeding of small bowel origin is suggested by the results of the study.
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Enfermedad de Crohn/diagnóstico , Endoscopios Gastrointestinales , Endoscopía Gastrointestinal , Hemorragia Gastrointestinal/etiología , Adolescente , Adulto , Anciano , Niño , Enfermedad de Crohn/complicaciones , Endoscopía Gastrointestinal/métodos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To describe the kinetics of leukocyte migration into a distal joint during the development of chronic inflammation in a murine model of rheumatoid arthritis (RA), to identify leukocyte subpopulations recruited in the synovial vessels, and to test in real time the effects of an antiinflammatory compound on leukocyte-endothelial cell interactions in the arthritic joint. METHODS: We used intravital video microscopy (IVM), which was adapted to the microcirculation of the mouse ankle, to monitor the kinetics of leukocyte-endothelium interactions (rolling and firm adhesion) during the onset and progression of proteoglycan-induced arthritis (PGIA), a chronic autoimmune model of RA. Subpopulations of rolling and adherent leukocytes were identified by in vivo immunostaining. Leukocyte extravasation into the ankle joint was verified histologically. RESULTS: Between the onset of arthritis and the beginning of the destructive phase of PGIA, we found a steady increase in the number of leukocytes that exhibited firm adherence to the endothelium of synovial vessels, which clearly underscores the chronic, self-perpetuating character of joint inflammation in this autoimmune model. We showed, however, that granulocytes, and not T cells, constituted the major cell population that was continuously recruited to the inflamed ankle. Using IVM, we could detect instant changes in leukocyte adhesion behavior in the synovial vessels of the arthritic joint upon administration of a compound that antagonizes leukocyte rolling. CONCLUSION: IVM of the microcirculation of the mouse ankle could become an essential tool for investigating the mechanisms that regulate leukocyte migration to the joint in systemic models of RA as well as for preclinical testing of antiinflammatory therapies.
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Articulación del Tobillo/patología , Artritis Reumatoide/patología , Movimiento Celular/inmunología , Leucocitos/patología , Microscopía por Video/métodos , Animales , Articulación del Tobillo/inmunología , Antineoplásicos/farmacología , Artritis Reumatoide/inmunología , Modelos Animales de Enfermedad , Femenino , Cinética , Rodamiento de Leucocito/efectos de los fármacos , Rodamiento de Leucocito/inmunología , Ratones , Ratones Endogámicos BALB C , Microscopía por Video/instrumentación , Polisacáridos/farmacologíaRESUMEN
CD44 and l-selectin (CD62L) are major adhesion receptors that mediate leucocyte recruitment at inflammatory sites and lymph nodes, by supporting cell rolling under blood flow. Both CD44 and CD62L have been implicated in inflammatory skin disorders, but their specific involvement in an immediate-type allergic reaction remains uncertain. We used mice deficient in CD44 or CED62L or both in order to determine whether one or both of these molecules were required for leucocyte extravasation in an atopic dermatitis-like allergic response. Wild-type (WT) mice and mice deficient in CD44, CD62L or both were immunized with ovalbumin (OVA). Inflammatory reaction in the ear was elicited once by means of intradermal injection of OVA. Effective sensitization of CD62L knockout (KO) mice required intraperitoneal antigen injection; however, OVA-specific T helper 2 (Th2)-type immune responses and IgE production in mice lacking CD44, CD62L or both were comparable to those in WT mice following intraperitoneal immunization. We employed intravital videomicroscopy to monitor the recruitment of fluorescence-labelled leucocytes to the ear tissue following challenge with OVA. The number of adherent leucocytes was significantly reduced in CD44 KO and CD44/CD62L double KO mice, indicating that CD44 was involved in firm adhesion, the committed step of leucocyte extravasation. Histology of the OVA-challenged ears showed a diminished leucocyte infiltration in the ears of CD44 KO and double KO mice. The results of our study demonstrate that CD44, but not CD62L, is required for leucocyte extravasation during a Th2-type inflammatory response.
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Dermatitis Alérgica por Contacto/patología , Receptores de Hialuranos/fisiología , Selectina L/fisiología , Leucocitos/metabolismo , Piel/metabolismo , Animales , Movimiento Celular , Dermatitis Alérgica por Contacto/metabolismo , Modelos Animales de Enfermedad , Genotipo , Inmunoglobulina E/química , Inmunoglobulina E/metabolismo , Inmunoglobulina G/metabolismo , Inmunohistoquímica , Inflamación , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Cinética , Linfocitos/metabolismo , Ratones , Ratones Noqueados , Ovalbúmina/metabolismo , Piel/citología , Células Th2 , Factores de TiempoRESUMEN
According to literature data autotransplantation of thyroid tissue for postoperative hypothyroidism remain controversial in the clinical praxis. The aim of this study was to examine the possibility of autotransplantation of cryopreserved (196 degrees C) thyroid tissue pieces in the sternocleidomastoid muscles and in the "apron" formed by the flaps of the greater omentum, and to evaluate their function postoperatively in dogs. Twelve adult mongrel dogs were used in the study. Total thyroidectomy was carried out in all animals. The removed thyroid lobes were cut into 3-4 mm pieces and cryopreserved to -196 degrees C. The cryopreserved thyroid tissue pieces were inserted in the sternocleidomastoid muscle and into the greater omentum. Determination of T3 and T4 levels was carried out pre- and postoperatively. Before sacrificing the surviving animals, total body scans were performed using J131 isotope to assess the function and position of autotransplants. The isotope activity of transplants from the sacrificed animals was evaluated quantitatively and their structures studied histologically. The starting values of T3 and T4 levels of animals were between 0.5 and 0.62 mmol/l and between 10.4 and 14.3 mmol/l respectively. On the 4-6th postoperative days the T3 and T4 levels of all surviving animals decreased close to zero, but from the 7-8th days they gradually increased and in weeks 3-4 reached their starting values. Isotope scans of both the sternocleidomastoid region and the greater omentum showed a significant rise in activity, which was highly different from that of surrounding tissues. Quantitative data obtained by the ROI technique correlated with values obtained after removal of the labelled tissues. The presence of thyroid tissue in the labelled ones was histologically justified. The results show that is possible to preserve the function of cryopreserved thyroid segments from totally thyroidectomized dogs by autotransplanting the segments into the muscles of the neck or into the omentum.
Asunto(s)
Criopreservación , Glándula Tiroides/trasplante , Tiroidectomía , Tiroxina/sangre , Triyodotironina/sangre , Animales , Perros , Epiplón/cirugía , Factores de Tiempo , Trasplante AutólogoRESUMEN
Cbl-b negatively regulates CD28-dependent T cell activation. In this report, we tested the hypothesis that CD28 and CTLA-4 have opposite roles in tuning T cell activation threshold by controlling the levels of Cbl-b protein expression. We demonstrate that CD28 costimulation potentiates TCR-induced Cbl-b degradation, whereas CTLA-4-B7 interaction is required for Cbl-b re-expression. In support of this finding, Cbl-b expression in CTLA-4 knockout (KO) T cells is significantly reduced, and treating CTLA-4KO mice with human CTLA-4Ig to block CD28-B7 interaction restores Cbl-b expression on T cells. Furthermore, CD28 and CTLA-4 costimulatory effects are compromised in Cbl-bKO T cells. These observations indicate that CD28 and CTLA-4 tightly regulate Cbl-b expression which is critical for establishing the threshold for T cell activation.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/fisiología , Antígenos de Diferenciación/fisiología , Antígenos CD28/fisiología , Activación de Linfocitos/inmunología , Subgrupos de Linfocitos T/inmunología , Ubiquitina-Proteína Ligasas/fisiología , Abatacept , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Proteínas Adaptadoras Transductoras de Señales/genética , Adyuvantes Inmunológicos/farmacología , Animales , Antígenos CD , Antígenos de Diferenciación/genética , Antígeno B7-1/metabolismo , Antígeno B7-1/farmacología , Antígenos CD28/genética , Antígeno CTLA-4 , Proliferación Celular , Células Cultivadas , Sinergismo Farmacológico , Femenino , Inhibidores de Crecimiento/farmacología , Humanos , Inmunoconjugados/farmacología , Activación de Linfocitos/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Proto-Oncogénicas c-cbl , Subgrupos de Linfocitos T/citología , Subgrupos de Linfocitos T/metabolismo , Ubiquitina-Proteína Ligasas/biosíntesis , Ubiquitina-Proteína Ligasas/deficiencia , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
OBJECTIVE: To gain insight into the mechanisms of the antiinflammatory effect of tumor necrosis factor alpha (TNFalpha)-induced protein 6 (Tnfip6) in arthritis, using Tnfip6-deficient animals. METHODS: TNFalpha-stimulated gene 6 (TSG-6) coding for Tnfip6 was disrupted. Tnfip6-deficient mice were backcrossed into proteoglycan-induced arthritis (PGIA)-susceptible BALB/c mice, and arthritis was induced by systemic immunization with cartilage proteoglycan (PG). Thioglycollate-induced sterile peritonitis was also assessed, to monitor the early events of neutrophil extravasation in wild-type and Tnfip6-deficient mice in the presence or absence of treatment with recombinant murine Tnfip6. RESULTS: The onset of PGIA was similar, but progression and severity were significantly greater, in Tnfip6-deficient mice compared with wild-type BALB/c mice. However, this was not associated with enhanced T or B cell responses to cartilage PGs, but rather, an early and more extensive infiltration of the synovium with neutrophil leukocytes was the most prominent histopathologic feature of PGIA in Tnfip6-deficient mice. This was accompanied by elevated serum levels of interleukin-6 and amyloid A, and significantly increased activities of the enzymes plasmin, myeloperoxidase, and neutrophil elastase in the inflamed paw joints of Tnfip6-null mice, when compared with that of the wild-type littermates. Loss of control over several components of inflammation resulted in extensive and rapid cartilage degradation, bone erosion, joint ankylosis, and deformities in Tnfip6-null animals. In support of the antiinflammatory effect of Tnfip6 via the inhibition of polymorphonuclear (PMN) cell efflux, neutrophil invasion during thioglycollate-induced peritonitis was 2-fold higher in Tnfip6-deficient animals than in wild-type animals, but was dramatically suppressed by intravenous injection of recombinant murine Tnfip6. CONCLUSION: Tnfip6 is a multifunctional antiinflammatory protein that is produced at the site of inflammation and can be retained by the hyaluronan-rich extracellular matrix. A major effect of Tnfip6 is the inhibition of the extravasation of PMN cells, predominantly neutrophils, into the site of inflammation, most likely via a CD44/hyaluronan/Tnfip6-mediated blocking mechanism.