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1.
J Helminthol ; 96: e45, 2022 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-35762233

RESUMEN

The alveolar hydatid disease, also known as alveolar echinococcosis, of humans is certainly one of the most dangerous zoonoses worldwide. The disease is caused by Echinococcus multilocularis - the fox tapeworm. Red foxes (Vulpes vulpes) are currently counted as the most important carriers (reservoirs) of E. multilocularis in the Northern Hemisphere. The possible routes of infection of E. multilocularis to humans are complex and still require research. Until now, it has been unknown whether E. multilocularis eggs can be moved by wind at all. This analysis shows, based on calculations, that E. multilocularis eggs can be transported by wind. Using a mathematical model, flight distances depending on wind speed and take-off heights are calculated for dense and less dense (coniferous) forest areas. The results - differentiated for seasons and as overall average - are based on mean values of wind speeds which were measured over a ten-year period in an experimental forest stand in the Solling (Germany). Due to their rate of descent, wind-related spreading of E. multilocularis eggs is possible. The average flight distance covered by E. multilocularis eggs in forest areas, depending on their starting altitude and wind speed, is between approximately 1.3 m and approximately 17 m. From the mathematical point of view, the wind factor can definitely be seen as one of the multiple vectors associated with environmental contamination by E. multilocularis eggs. Consequently, the possible wind-borne spread of E. multilocularis eggs poses an infection risk to humans that should be considered and requires further research.


Asunto(s)
Equinococosis , Echinococcus multilocularis , Animales , Equinococosis/veterinaria , Zorros , Humanos , Viento
2.
Brain Stimul ; 12(5): 1111-1120, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31031208

RESUMEN

BACKGROUND: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. METHODS: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (<4 weeks), postoperative (4 weeks < 6 months) and long term AEs (>6 months). RESULTS: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ±â€¯4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ±â€¯4.1 years (range 3 months-15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7-9 years beyond 6 months after implantation. DISCUSSION: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. CONCLUSION: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.


Asunto(s)
Estimulación Encefálica Profunda/efectos adversos , Trastornos Distónicos/epidemiología , Trastornos Distónicos/terapia , Electrodos Implantados/efectos adversos , Adolescente , Niño , Trastornos Distónicos/diagnóstico , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Masculino , Infección de la Herida Quirúrgica/diagnóstico , Infección de la Herida Quirúrgica/epidemiología
3.
Eur J Clin Nutr ; 71(8): 995-1001, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28378853

RESUMEN

BACKGROUND/OBJECTIVES: Fatty liver disease (FLD) is an important intermediate trait along the cardiometabolic disease spectrum and strongly associates with type 2 diabetes. Knowledge of biological pathways implicated in FLD is limited. An untargeted metabolomic approach might unravel novel pathways related to FLD. SUBJECTS/METHODS: In a population-based sample (n=555) from Northern Germany, liver fat content was quantified as liver signal intensity using magnetic resonance imaging. Serum metabolites were determined using a non-targeted approach. Partial least squares regression was applied to derive a metabolomic score, explaining variation in serum metabolites and liver signal intensity. Associations of the metabolomic score with liver signal intensity and FLD were investigated in multivariable-adjusted robust linear and logistic regression models, respectively. Metabolites with a variable importance in the projection >1 were entered in in silico overrepresentation and pathway analyses. RESULTS: In univariate analysis, the metabolomics score explained 23.9% variation in liver signal intensity. A 1-unit increment in the metabolomic score was positively associated with FLD (n=219; odds ratio: 1.36; 95% confidence interval: 1.27-1.45) adjusting for age, sex, education, smoking and physical activity. A simplified score based on the 15 metabolites with highest variable importance in the projection statistic showed similar associations. Overrepresentation and pathway analyses highlighted branched-chain amino acids and derived gamma-glutamyl dipeptides as significant correlates of FLD. CONCLUSIONS: A serum metabolomic profile was associated with FLD and liver fat content. We identified a simplified metabolomics score, which should be evaluated in prospective studies.


Asunto(s)
Hígado Graso Alcohólico/sangre , Metabolismo de los Lípidos , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/sangre , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Bancos de Muestras Biológicas , Biomarcadores/sangre , Estudios de Cohortes , Biología Computacional , Estudios Transversales , Dipéptidos/sangre , Sistemas Especialistas , Hígado Graso Alcohólico/diagnóstico por imagen , Hígado Graso Alcohólico/metabolismo , Hígado Graso Alcohólico/fisiopatología , Femenino , Ácido Glutámico/análogos & derivados , Ácido Glutámico/sangre , Humanos , Hígado/diagnóstico por imagen , Hígado/fisiopatología , Imagen por Resonancia Magnética , Masculino , Metabolómica/métodos , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Autoinforme , Índice de Severidad de la Enfermedad
4.
Eur J Gynaecol Oncol ; 37(6): 820-826, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-29943929

RESUMEN

OBJECTIVE: This study aimed to identify indicators for an increased frequency of recurrent or metastatic disease in women with mammary carcinoma staged negative for nodal involvement. MATERIALS AND METHODS: 202/270 patients (age: mean 57.5, range 24-83 years) with histologically confirmed early stage mammary carcinoma negative for metastasis to the sentinel lymph nodes (SLN) were observed with respect to their clinical course for a mean period of 3.6 years following SLN extirpation. RESULTS: Forty of 202 patients with negative SLN underwent chemotherapy (38/188 in the recurrence-free group vs. 2/14 in the group with progressive disease) and 79% of both subcollectives did not undergo chemotherapy. Seven of 188 of patients in the recurrence-free group received immunotherapy and none of the patients in the group with disease progression were treated with this modality. One hundred sixty-two of 202 patients with negative SLN underwent hormone therapy, 157/188 in the recurrence-free group and 5/14 in the group with disease progression. One hundred sixty-four of 202 patients with negative nodal status received adjuvant radiation therapy of the affected breast, 156/188 in the recurrence-free group and 8/14 in the group with disease progression. CONCLUSIONS: When assessing the risk profile for disease recurrence or the occurrence of metastatic disease, statistically significant differences with respect to disease progression were identified for the parameters chemo-, antibody, hormone, and radiation therapy. The preliminary observations of this study show that even those patients in an early disease stage and with negative SLNs profit from these adjuvant non-surgical therapy options.


Asunto(s)
Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/epidemiología , Ganglio Linfático Centinela/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia
5.
Eur J Surg Oncol ; 40(1): 96-102, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24139636

RESUMEN

PURPOSE: Evaluation if cryoablation of small renal tumours (RT) would facilitate the technique of laparoscopic partial nephrectomy (LPN) in a prospective study. PATIENTS AND METHODS: In a prospective non-randomised study between April 2007 and October 2009, 16 patients with a mean age of 68 years (48-80 years) and a peripherally located RT were candidates for nephron-sparing surgery (5 open partial nephrectomy (OPN), 11 LPN). Cryoablation of RT was followed in the same session by open (K-OPN) and laparoscopic (K-LPN) partial nephrectomy. Perioperative and follow-up parameters were estimated. A matched-pair cohort of 41 patients (20 OPN, 21 LPN) who underwent standard operations due to the same indication has been selected for retrospective comparison (controls). RESULTS: Mean age for K-OPN was 74 years (69-83) with mean blood loss 140 ml (50-200); for K-LPN: 66.6 years (48-80) with 100 ml (50-700). All procedures were completed successfully without conversions (K-LPN), transfusions or intra-operative complications. Compared to OPN/LPN, K-OPN and K-LPN were associated with a longer operative time (P < 0.05) and a comparable postoperative hospital stay. There were no early postoperative complications. Cryoablation has not affected the histopathological evaluation of tumours or resection margins. Histopathology showed cytologic changes suggesting fresh coagulative necrosis, glomerular vascular congestion and interstitial haemorrhages following cryotherapy. One patient (K-LPN) developed a pararenal abscess necessitating puncture after 7 weeks. The follow-up (9-42 months) was uneventful. CONCLUSIONS: The current study shows that K-LPN is feasible without increasing procedure morbidity or compromising surgical and oncological outcomes. It adds no advantage to tumour excision. Pathological findings document early cryoablation effects but viable tissue.


Asunto(s)
Carcinoma de Células Renales/cirugía , Criocirugía , Neoplasias Renales/cirugía , Nefrectomía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Nefrectomía/métodos , Tempo Operativo , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
6.
Nuklearmedizin ; 52(1): 14-20, 2013.
Artículo en Alemán | MEDLINE | ID: mdl-23389730

RESUMEN

UNLABELLED: The sentinel lymph node (SLN) is of considerable prognostic relevance, because extended lymph node dissection may not be performed in patients presenting with histologically negative SLN. The aim of this study was to prove the prognostic value of the SLN-concept in these patients in long term follow-up. PATIENTS, METHODS: The clinical follow-up of 202 women with histologically proven breast cancer and metastatically uninvolved (negative) SLN, as determined using Tc-99m-nanocolloid, was observed for a mean period of 43.4 months. Histological examination included standard methods (HE-Test) and special histochemical techniques (antibodies against cytokeratin). All patients underwent clinical examinations and mamography according a standardised schema; other procedures like ultrasound examination, routine blood tests, and chest X-ray scans were performed in patients considered doubtful after clinical examination or mamography. RESULTS: Despite of negative SLN-findings in 14/202 patients (6.9%) metastases were found after a mean time period of 35.9 months. 4 patients showed local re-lapses, 3 patients presented with regional lymph node recurrences in the previously mapped (negative) SLN-basin, and 7 Patients developed distant metastases outside the primary lymphatic basin. CONCLUSION: In patients negative on SLN-biopsy the axillary lymph-node-recurrence-rate was low; in 3/202 patients (1.5%) a progression in the SLN-basin could be assessed, being real concept failures. Our results underline that there is no evidence to question this concept in patients presented with clinically metastatically uninvolved early stage of breast cancer.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Carcinoma/diagnóstico , Carcinoma/secundario , Biopsia del Ganglio Linfático Centinela/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/epidemiología , Reacciones Falso Negativas , Femenino , Alemania/epidemiología , Humanos , Metástasis Linfática , Persona de Mediana Edad , Prevalencia , Medición de Riesgo
7.
Digestion ; 86(4): 338-48, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23207185

RESUMEN

PURPOSE: To evaluate the efficiency of a multimodality approach consisting of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) as bridging therapy for patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT) and to evaluate the histopathological response in explant specimens. MATERIALS AND METHODS: Between April 2001 and November 2011, 36 patients with 50 HCC nodules (1.4-5.0 cm, median 2.8 cm) on the waiting list for liver transplantation were treated by TACE and RFA. The drop-out rate during the follow-up period was recorded. The local efficacy was evaluated by histopathological examination of the explanted livers. RESULTS: During a median follow-up time of 29 (4.0-95.3) months the cumulative drop-out rate for the patients on the waiting list was 0, 2.8, 5.5, 11.0, 13.9 and 16.7% at 3, 6, 12, 24, 36 and 48 months, respectively. 16 patients (with 26 HCC lesions) out of 36 (44.4%) were transplanted by the end of study with a median waiting list time of 13.7 (2.5-37.8) months. The histopathological examination of the explanted specimens revealed a complete necrosis in 20 of 26 HCCs (76.9%), whereas 6 (23.1%) nodules showed viable residual tumor tissue. All transplanted patients are alive at a median time of 29.9 months. Imaging correlation showed 100% specificity and 66.7% sensitivity for the depiction of residual or recurrent tumor. CONCLUSION: We conclude that TACE combined with RFA could provide an effective treatment to decrease the drop-out rate from the OLT waiting list for HCC patients. Furthermore, this combination therapy results in high rates of complete tumor necrosis as evaluated in the histopathological analysis of the explanted livers. Further randomized trials are needed to demonstrate if there is a benefit in comparison with a single-treatment approach.


Asunto(s)
Carcinoma Hepatocelular/terapia , Ablación por Catéter , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Recurrencia Local de Neoplasia/diagnóstico , Adulto , Anciano , Carcinoma Hepatocelular/patología , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasia Residual , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Tiempo , Listas de Espera
8.
Urologe A ; 50(9): 1106-9, 2011 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-21735267

RESUMEN

BACKGROUND: According to the recently published German-language S3 guidelines, various treatment options such as surgical management or radiation therapy are available to patients with locally advanced prostate cancer. METHODS: Particularly the establishment of minimally invasive endoscopic surgical techniques, which provide better optical images, has made it possible to visualize tissue layers that are usually difficult to identify with the open surgical technique. This contribution describes a pilot study on the establishment of open intrafascial radical prostatectomy. AIM: The goal of the study is to critically analyze both the functional and especially the oncological results, which should not be compromised by the nerve-sparing approach.


Asunto(s)
Fasciotomía , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Selección de Paciente , Neoplasias de la Próstata/patología
10.
Bone Marrow Transplant ; 45(7): 1181-8, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19915632

RESUMEN

There is growing evidence that GVHD affects the central nervous system (CNS). In this study, we describe the long-term follow-up of four allogeneic BM recipients who developed cerebral angiitis-like disease probably due to GVHD. The patients developed focal neurological signs, cognitive deficits and/or coma in association with GVHD, 2-18 years after transplantation, following reduction of immunosuppressive therapy. Magnetic resonance imaging was variable, showing generalized brain atrophy, ischemic lesions or leukoencephalopathy. Diagnosis of cerebral angiitis was confirmed by histopathological analysis of bioptic brain tissue and response to immunosuppressive therapy. By means of immunohistochemistry and immunofluorescence, perivascular lymphomononuclear cerebral infiltrates were shown to express the adhesion receptor, CD11a, and the chemokine receptor, CCR5. Our findings imply that GVHD should be considered in the differential diagnosis of noninfectious angiitis-like disease of the CNS in long-term survivors after allogeneic BMT. Infiltrating cells, in analogy to typical target organs of GVHD such as skin or liver, expressed CD11a and CCR5. These findings could be of etiopathological, diagnostic and therapeutic relevance.


Asunto(s)
Enfermedad Injerto contra Huésped/complicaciones , Inmunosupresores/farmacología , Vasculitis del Sistema Nervioso Central/diagnóstico , Vasculitis del Sistema Nervioso Central/etiología , Adulto , Trasplante de Médula Ósea/efectos adversos , Antígeno CD11a/análisis , Movimiento Celular/inmunología , Enfermedad Crónica , Diagnóstico Diferencial , Femenino , Enfermedad Injerto contra Huésped/diagnóstico , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Receptores CCR5/análisis , Sobrevivientes , Trasplante Homólogo , Vasculitis del Sistema Nervioso Central/patología , Adulto Joven
11.
Urologe A ; 49(4): 540-2, 2010 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-19943029
12.
Eur J Med Res ; 14(6): 272-6, 2009 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-19541588

RESUMEN

Dysplasia epiphysealis hemimelica (DEH) or Trevor's Disease is a very rare disease with an estimated incidence of one in 1.000.000. The majority of cases reported affect the lower limb and only 25 case reports of 33 cases with affection of the upper limb have been published. Here we present a case of DEH affecting the distal ulnar epiphysis and the lunate in an eleven-year-old girl, a DEH location described extremely rarely before. We firstly do not only present clinical and radiological findings (plane radiographs, CT, MRI), but also the surgical approach and the histopathological results of DEH in this uncommon location. Although extremely rare, DEH should be considered also in non-typical locations.


Asunto(s)
Neoplasias Óseas/patología , Osteocondrodisplasias/patología , Osteocondroma/patología , Cúbito/patología , Neoplasias Óseas/cirugía , Niño , Epífisis/patología , Femenino , Humanos , Osteocondrodisplasias/fisiopatología , Osteocondrodisplasias/cirugía , Osteocondroma/cirugía , Radiografía , Rango del Movimiento Articular , Resultado del Tratamiento , Cúbito/diagnóstico por imagen
13.
Lancet ; 357(9252): 282-3, 2001 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-11214135

RESUMEN

A case of colonoscopy-induced hyponatraemic encephalopathy led us to study the risk of hyponatraemia after gastrointestinal endoscopy. We assessed 40 patients before and after colonoscopy. 20 gastroscopy patients served as controls. Our findings show a high incidence (7.5%) of hyponatraemia after colonoscopy, in association with raised serum concentrations of arginine vasopressin. Physicians should be aware of this complication, since it may contribute to psychological and neurological symptoms after colonoscopy.


Asunto(s)
Colonoscopía/efectos adversos , Hiponatremia/etiología , Arginina Vasopresina/sangre , Encefalopatías/etiología , Femenino , Gastroscopía/efectos adversos , Humanos , Persona de Mediana Edad , Estudios Prospectivos
14.
Ann Rheum Dis ; 60(1): 36-42, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11114280

RESUMEN

OBJECTIVE: To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon gamma (IFNgamma), interleukin 4 (IL4), tumour necrosis factor alpha (TNFalpha), and IL10 at the single cell level in patients with AS in comparison with healthy HLA-B27 negative and HLA-B27 positive controls. METHODS: Peripheral blood mononuclear cells from 65 subjects (25 HLA-B27 positive patients with active AS, 18 healthy HLA-B27 positive controls, and 22 healthy HLA-B27 negative controls) were stimulated with phorbol myristate acetate/ionomycin for six hours, surface stained for CD3 and CD8, intracellularly stained for the cytokines IFNgamma, TNFalpha, IL4, and IL10, and analysed by flow cytometry. TNFalpha production was related to the genotype of the TNFalpha promoter at the -308 and -238 polymorphisms. RESULTS: In peripheral blood the percentage of TNFalpha+ T cells was significantly lower in HLA-B27 positive patients with AS (median 5.1% for CD4+ T cells) than in healthy HLA-B27 negative controls (median 9.5%; p=0.008). Surprisingly, the percentage of TNFalpha+ T cells was also significantly lower in healthy HLA-B27 positive controls (median 7.48%) than in healthy HLA-B27 negative controls (p=0.034). Furthermore, the percentage of IFNgamma+ T cells was lower in patients with AS and in healthy HLA-B27 positive controls than in healthy HLA-B27 negative controls (p=0.005 and p=0.003, respectively). The percentage of IL10+/CD8+ T cells was higher in patients with AS than in both control groups. In HLA-B27 positive subjects, TNF1/2 heterozygosity at -308 (n=6) was associated with a higher percentage of TNFalpha+ T cells than TNF1/1 homozygosity (n=25; median 9.97% v 5.11% for CD4+ T cells; p=0.017). In contrast, in HLA-B27 negative controls (n=18) there was no such genotype/phenotype correlation (median 9.4% v 10.6%). CONCLUSIONS: The lower T cell production of TNFalpha and IFNgamma shown at the single cell level in HLA-B27 positive patients with AS and healthy HLA-B27 positive controls may contribute to the increased susceptibility of HLA-B27 positive subjects to develop AS. Preliminary genotype-phenotype correlations suggest that in HLA-B27 positive subjects TNF2 at -308 or a linked gene results in higher TNFalpha production and, therefore, might be a marker for a protective haplotype.


Asunto(s)
Antígeno HLA-B27/análisis , Interferón gamma/biosíntesis , Espondilitis Anquilosante/inmunología , Subgrupos de Linfocitos T/inmunología , Factor de Necrosis Tumoral alfa/biosíntesis , Adulto , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Interleucina-10/biosíntesis , Masculino , Polimorfismo Genético , Regiones Promotoras Genéticas , Espondilitis Anquilosante/genética , Factor de Necrosis Tumoral alfa/genética
16.
Ann Rheum Dis ; 59(4): 311-4, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10733482

RESUMEN

OBJECTIVE: This study was performed to assess whether there is any change in the T cell cytokine pattern in early rheumatoid arthritis (RA) patients treated with methotrexate (MTX) and whether the lymphocytic cytokine pattern correlates with disease activity. METHODS: Eight patients with RA (disease duration < six months) were studied serially before, after three, and after six to nine months of treatment with MTX for the cytokines tumour necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), interleukin 4 (IL4) and interleukin 10 (IL10) by intracellular staining of T cells derived from peripheral blood. Response to treatment was assessed by the modified disease activitiy score. RESULTS: The clincial response was accompanied by a significant decrease of TNFalpha positive CD4(+) T cells from a median of 8.53% (interquartile range 5.83-10.91%) before treatment to 6.17% (2.15-6.81%) after six to nine months of treatment (p=0.021). Inversely, IL10 positive T cells increased from a median of 0.65% (interquartile range 0.6-0.93%) to a median of 1. 3% (1.22%-1.58%) after six to nine months of treatment (p=0.009). No significant change in the percentage of INFgamma positive T cells and a small decrease of IL4 positive T cells during treatment were observed. The percentage of IL4 positive CD4(+) T cells before treatment correlated with disease activity after six to nine months (r= -0.7066; p=0.05). CONCLUSIONS: During treatment of RA with MTX the percentage of TNFalpha producing T cells decreases whereas that of IL10 producing T cells increases. This may affect macrophage activation and, therefore, may represent a regulatory mechanism relevant to disease remission. Furthermore, the percentage of IL4 positive CD4(+) T cells at disease onset may be a useful prognostic marker.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Citocinas/metabolismo , Metotrexato/uso terapéutico , Subgrupos de Linfocitos T/inmunología , Artritis Reumatoide/inmunología , Biomarcadores/análisis , Linfocitos T CD4-Positivos/inmunología , Citometría de Flujo , Humanos , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Pronóstico , Estudios Prospectivos , Factor de Necrosis Tumoral alfa/metabolismo
17.
Rheumatology (Oxford) ; 38(11): 1058-67, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10556256

RESUMEN

OBJECTIVES: To quantify the T-helper type (Th) 1 cytokine interferon gamma (IFN-gamma)-positive and the Th2 cytokine interleukin (IL)-4-positive cells in synovial fluid (SF) and synovial membrane (SM) at the single-cell level in rheumatoid arthritis (RA) in comparison to reactive arthritis (ReA), and to manipulate the cytokine pattern of RA patients in vitro. METHODS: Eighteen patients with RA and 17 with ReA were studied. For intracellular staining of cytokines, SF mononuclear cells (MNC) from seven patients with RA, in comparison to eight patients with ReA, were triple stained with anti-IFN-gamma, IL-4 and anti-CD4 or anti-CD8 monoclonal antibodies (mAb) and analysed by flow cytometry. Furthermore, in 13 patients with RA, immunohistology of SM was performed and compared with seven ReA patients. In addition, in six of the RA patients, synovial T cells were grown over 3 weeks in the presence of various cytokines and intracellular cytokine staining analysed by flow cytometry weekly. RESULTS: In SF, the mean percentage of IFN-gamma+/CD4+ T cells in RA was almost 4-fold higher than the number of IL-4+/CD4+ T cells (11.3+/-5 vs 3.02+/-1.04; P=0.0012), while the ratio of IFN-gamma/IL-4+ CD4+ T cells was only 1.59 in ReA (P=0.047 for the ratio difference). A similar result was obtained for SM: the ratio of IFN-gamma/IL-4+ cells in RA was 4.3 (P<0.0001 for the IFN-gamma/IL-4 difference), but only 1.2 for ReA (P=0.02 for the ratio difference). Of the CD3+ cells in SM, 2.8% were positive for IFN-gamma and 0.4% for IL-4 in three RA patients. A decrease in the number of IFN-gamma-positive SF T cells and an increase in the number of IL-4-positive SF T cells could be achieved in vitro through IL-4, but not by IL-10 or transforming growth factor beta. CONCLUSIONS: The Th1 pattern in the joint of RA patients demonstrated at the single-cell level may be important for the pathogenesis of RA and may provide a target for future immunotherapy. Our data suggest a therapeutic role for IL-4.


Asunto(s)
Artritis Reumatoide/inmunología , Linfocitos T CD4-Positivos/inmunología , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Líquido Sinovial/inmunología , Membrana Sinovial/inmunología , Adolescente , Adulto , Anciano , Artritis Reactiva/inmunología , Artritis Reactiva/patología , Artritis Reumatoide/patología , Niño , Femenino , Humanos , Técnicas In Vitro , Interleucina-10/farmacología , Interleucina-12/metabolismo , Interleucina-4/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Prohibitinas , Membrana Sinovial/patología , Células TH1/efectos de los fármacos , Células TH1/inmunología , Factor de Crecimiento Transformador beta/farmacología , Factor de Necrosis Tumoral alfa/metabolismo
18.
Arthritis Rheum ; 42(10): 2039-44, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10524674

RESUMEN

OBJECTIVE: To determine Th1 and Th2 cytokine production in patients with reactive arthritis (ReA) in relation to disease outcome and in comparison with rheumatoid arthritis (RA). METHODS: Secretion of tumor necrosis factor alpha (TNFalpha), interferon-gamma, interleukin-10 (IL-10), and IL-4 by peripheral blood mononuclear cells (PBMC) from 53 patients with early ReA (disease duration <8 weeks, 64% HLA-B27 positive) and 30 patients with early, untreated RA (disease duration <6 months) was determined by enzyme-linked immunosorbent assay (ELISA) after ex vivo stimulation. Intracellular cytokine staining with quantification of positive T cells by fluorescence-activated cell sorting (FACS) was performed in 12 ReA patients and 12 RA patients. In 27 ReA patients, cytokine secretion was measured again after 3 months. Patients were followed up for 1 year, and cytokine patterns were correlated with disease duration. RESULTS: TNFalpha secreted by whole PBMC and by T cells was significantly lower, by ELISA and by FACS, in ReA patients than in RA patients, while no significant differences were detected for the other cytokines. ReA patients with a disease duration of > or =6 months showed significantly lower TNFalpha secretion than patients with a disease duration of <6 months (mean +/- SD 385 +/- 207 pg/ml versus 684 +/- 277 pg/ml; P = 0.003). Furthermore, low TNFalpha secretion after 3 months also correlated significantly with a more chronic course of disease. HLA-B27 positive patients secreted less TNFalpha than did those who were B27 negative (338 +/- 214 pg/ml versus 512 +/- 207 pg/ml; P = 0.05), and patients with a more chronic course had a higher frequency of B27 positivity (47% versus 80%; P = 0.01). Among the 27 HLA-B27 positive patients, TNFalpha secretion in those with a disease duration of > or = 6 months was lower than that in the 7 with a disease duration of <6 months (308 +/- 167 pg/ml versus 562 +/- 308 pg/ml; P = 0.04). CONCLUSION: Low TNFalpha secretion and HLA-B27 status correlate with longer disease duration in ReA patients, possibly with an additive effect. The diminished TNFalpha production might reflect a state of relative immunodeficiency contributing to bacterial persistence in ReA.


Asunto(s)
Artritis Reactiva/inmunología , Monocitos/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Artritis Reactiva/sangre , Artritis Reactiva/fisiopatología , Biomarcadores , Enfermedad Crónica , Citocinas/inmunología , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prohibitinas , Células TH1/inmunología , Células Th2/inmunología , Factor de Necrosis Tumoral alfa/inmunología
19.
Lab Invest ; 76(5): 661-70, 1997 May.
Artículo en Inglés | MEDLINE | ID: mdl-9166285

RESUMEN

Extending our previous efforts to characterize ovarian neoplasms by interphase cytogenetics, we analyzed a series of 32 mucinous tumors by nonisotopic in situ hybridization with seven different centromere-specific probes as well as by flow and image DNA cytometry; we then compared the data with results of p53 and Ki67 immunohistochemistry and MYC DNA-PCR analysis and of the clinical follow-ups. Of the tumors studied, 11 of 14 (78.6%) mucinous carcinomas, 7 of 7 (100%) mucinous tumors of low malignant potential (LMP), and 7 of 11 (63.6%) mucinous cystadenomas demonstrated chromosomal aberrations. The mean number of chromosomal aberrations (+/- SD) was slightly higher in DNA cytometrically nondiploid cases than in diploid cases (2.0 +/- 1.6 versus 1.6 +/- 1.2, not significant) but did not differ significantly among the study groups (carcinomas: 1.7 +/- 1.4; tumors of LMP; 1.9 +/- 0.7; adenomas: 1.4 +/- 1.4). Aberrations affected chromosomes 1 (14 of 27 cases) and 6 (12 of 31) most frequently, followed by chromosomes 17 (7 of 28), 7 (6 of 29), and X (6 of 28). Signal gain for centromere 1, which was the most prevalent finding (13 of 27), was observed in 3 of 10 mucinous cystadenomas, 2 of 4 mucinous tumors of LMP, and 8 of 13 mucinous carcinomas. All six moderately and poorly differentiated carcinomas demonstrated this aberration. Signal gain of centromere 6 (3 of 13) and centromere 7 (4 of 13) were found only in carcinomas (p < 0.05 and p < 0.025, respectively). The interphase cytogenetic results correlated neither with proliferative activity, immunohistochemical p53 accumulation, MYC DNA amplification, nor postoperative outcome. Compared with serous ovarian neoplasms (Lab Invest 1996, 75:473-485), mucinous tumors demonstrated signal gain for chromosome 1 (p < 0.0001) and signal loss for chromosomes 6 (p < 0.001) and X (p < 0.01) significantly more often. Loss of centromere 17 was more characteristic for serous than for mucinous carcinomas (p < 0.05). Our observations show that chromosomal aberrations in mucinous ovarian neoplasms are apparently not random. These results support the notion that the molecular genetic changes in mucinous neoplasms differ from those in serous tumors.


Asunto(s)
Adenocarcinoma Mucinoso/genética , Cistoadenoma Mucinoso/genética , Citogenética/métodos , Interfase/genética , Neoplasias Ováricas/genética , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , División Celular/genética , Aberraciones Cromosómicas/genética , Cistoadenoma Mucinoso/patología , ADN de Neoplasias/análisis , Femenino , Humanos , Hibridación in Situ , Antígeno Ki-67/genética , Persona de Mediana Edad , Neoplasias Ováricas/patología , Ploidias
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