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1.
Neth J Med ; 77(5): 183-185, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31264583
3.
Clin Exp Immunol ; 174(2): 256-64, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23901889

RESUMO

Graves' disease (GD) is an autoimmune disease that involves aberrant B and T lymphocyte responses. Detailed knowledge about lymphocyte subpopulation composition will therefore enhance our understanding of the pathogenesis of GD and might support the development of new immunomodulatory treatment approaches. The aim of this study was to gain detailed insight into the composition of the peripheral blood lymphocyte compartment in GD before and during anti-thyroid drug therapy. Major B and T lymphocyte subpopulations were investigated by flow cytometry in peripheral blood from newly diagnosed GD patients (n = 5), GD patients treated with anti-thyroid drugs (n = 4), patients with recurrent GD (n = 7) and healthy controls (HC; n = 10). In GD patients, numbers of activated T lymphocytes [human leucocyte antigen D-related (HLA-DR)⁺ and CD25⁺] were increased. The B lymphocyte compartment in GD was characterized by significantly higher numbers of transitional (CD38(high) CD27⁻, P < 0.03) and pre-naive mature (CD38(low) CD27⁻ IgD⁺ CD5⁺, P < 0.04) B lymphocytes, while memory populations were slightly decreased. The increased numbers of CD5⁺, transitional and pre-naive mature B lymphocytes correlated positively with fT4 plasma levels. GD is associated with increased numbers of activated T lymphocytes and transitional and pre-naive mature CD5⁺ B lymphocytes within the peripheral blood. The increase in CD5⁺ B lymphocytes was due mainly to an increase in transitional and pre-naive mature B lymphocytes. Increased fT4 plasma levels might be associated with this increase in transitional and pre-naive mature CD5⁺ B lymphocytes.


Assuntos
Circulação Sanguínea/imunologia , Doença de Graves/imunologia , Subpopulações de Linfócitos/imunologia , Células Progenitoras Linfoides/imunologia , Linfócitos T/imunologia , Adulto , Antígenos CD/metabolismo , Diferenciação Celular , Proliferação de Células , Feminino , Antígenos HLA-DR/metabolismo , Humanos , Memória Imunológica , Imunofenotipagem , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Thyroid ; 14(4): 271-5, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15142360

RESUMO

Studies in hypothyroid rats show that, when infused with a combination of thyroxine (T4) plus triiodothyronine (T3) to normalize thyrotropin (TSH), euthyroidism in all organs is only ensured when T(4) and T(3) are administered in a ratio as normally secreted by the rat thyroid. As substitution with T(4)-only results in an abnormal serum T(4)/T(3) ratio, it is also possible that in humans, euthyroidism does not exist at the tissue level in many organs, considering that iodothyronine metabolism in the human and the rat share many similar mechanisms. Recent reports in which cognitive function and well-being are compared in patients with primary hypothyroidism substituted with T(4)-only versus substitution with T(4) plus T(3) result in controversial findings in that either positive or no effects were found. In all these studies T(3) was used in the plain form that results in nonphysiologic serum T(3) peaks. In these studies it is suggested that substitution with T(3 )should preferably be performed with a preparation that slowly releases T(3) to avoid these peaks. In the study reported here we show that treatment of hypothyroid subjects with a combination of T(4) plus slow-release T(3) leads to a considerable improvement of serum T(4) and T(3) values, the T(4)/T(3) ratio and serum TSH as compared to treatment with T(4)- only. Serum T(3) administration with slow-release T(3) did not show serum peaks, in contrast to plain T(3).


Assuntos
Hipotireoidismo/tratamento farmacológico , Tiroxina/uso terapêutico , Tri-Iodotironina/uso terapêutico , Área Sob a Curva , Estudos Cross-Over , Preparações de Ação Retardada , Quimioterapia Combinada , Feminino , Humanos , Masculino , Tiroxina/sangue , Tiroxina/farmacocinética , Tri-Iodotironina/sangue , Tri-Iodotironina/farmacocinética
5.
Eur J Nucl Med ; 23(11): 1508-13, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8854850

RESUMO

Substance P, an 11-amino acid neuropeptide, has an important role in modulating pain transmission through neurokinin 1 and 2 receptors. Substance P and other tachykinins may also play a role in the pathogenesis of inflammatory diseases. In this study we present the results concerning the metabolism of the substance P analogue [111In-DTPA-Arg1]-substance P in man, as well as the visualization of the thymus in patients with immune-mediated diseases. Twelve selected patients were investigated, comprising five with inflammatory bowel disease, one with ophthalmic Graves' disease, one with sclerosing cholangitis, one with Sjögren's syndrome, one with rheumatoid arthritis, one with systemic lupus erythematosus and two with myasthenia gravis. During and after intravenous administration of 150-250 MBq (2.5-5.0 microg) [111In-DTPA-Arg1]-substance P, blood pressure, heart rate and oxygen saturation were monitored. Radioactivity was measured in blood, urine and faeces during the 48 h after injection. Planar and single-photon emission tomographic images were obtained 4 and 24 h after injection. After administration of [111In-DTPA-Arg1]-substance P, a transient flush was observed in all patients. Degradation of [111In-DTPA-Arg1]-substance P started in the first minutes after administration, resulting in a half-life of 10 min for the total plasma radioactivity, and of 4 min for the intact radiopharmaceutical, as identified with high-performance liquid chromatography. Urinary excretion accounted for >95% of the radioactivity within 24 h post injection, and up to 0.05% was found in the faeces up to 60 h. In all patients uptake of radioactivity was found in the areolae mammae (in women), liver, spleen, kidneys and urinary bladder. In eight patients a high uptake of [111In-DTPA-Arg1]-substance P was observed in the thymus. We conclude that, despite its short half-life, [111In-DTPA-Arg1]-substance P, a new radiopharmaceutical, can be used to visualize the thymus. This may contribute to the investigation of the role of thymus in immune-mediated diseases. In addition, inflammatory sites in various diseases could be visualized.


Assuntos
Doenças Autoimunes/diagnóstico por imagem , Radioisótopos de Índio , Ácido Pentético/análogos & derivados , Receptores da Neurocinina-1/metabolismo , Substância P/análogos & derivados , Substância P/metabolismo , Timo/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cintilografia , Timo/imunologia , Timo/metabolismo
6.
Diabetes Care ; 19(10): 1122-5, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8886560

RESUMO

OBJECTIVE: The mechanisms by which diabetes leads to rapidly progressive atherosclerosis are not fully understood. Adherence of monocytes to the arterial wall is an early event in the development of atherosclerotic lesions. RESEARCH DESIGN AND METHODS: The binding of freshly isolated monocytes from patients with NIDDM, IDDM, and healthy control subjects to a monolayer of endothelial cells obtained from human umbilical vein was investigated. RESULTS: Endothelial adherence of monocytes from normolipidemic patients with IDDM (15.8 +/- 4.5%) or NIDDM (16.9 +/- 4.6%) was comparable to that of monocytes from a control population (15.3 +/- 3.5%). In patients with NIDDM with a serum triglyceride concentration > 2.5 mmol/l, the percentage of cells that adhere to endothelial cells in vitro was significantly increased (23.3 +/- 3.1%). Glycemic control did not correlate with monocyte adherence. The presence of symptomatic atherosclerotic disease, age, or sex was not associated with a change in monocyte binding in vitro. CONCLUSIONS: The results suggest that in NIDDM hypertriglyceridemia should be treated to reduce the high risk for atherosclerosis.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Endotélio Vascular/fisiologia , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Monócitos/fisiologia , Adulto , Adesão Celular , Células Cultivadas , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Valores de Referência , Triglicerídeos/sangue , Veias Umbilicais
7.
Eur J Gastroenterol Hepatol ; 8(9): 929-31, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8889464

RESUMO

A 40-year-old Turkish man on busulphan treatment for chronic myeloid leukaemia was hospitalized with steroid resistant (up to 100 mg prednisolone/24 h for over 4 weeks) colitis. On the basis of concomitant orogenital ulceration and unusual, deep punched out ulcers in the colon and smaller ulcers in the terminal ileum, Behçet's disease of the bowel, manifesting as ileocolitis, was diagnosed. Leukaemic infiltration, Crohn's colitis, neutropenic colitis and infectious colitis were excluded by histology and cultures. Treatment with colchicine 2 mg/day improved the orogenital ulcers but with only minor improvement of the colitis. Thalidomide treatment (400 mg/day), however, dramatically improved the colitis within 7 days: fever and diarrhoea disappearing. Colonoscopy after 4 weeks of treatment revealed previously giant ulcers practically healed.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Colite/etiologia , Imunossupressores/uso terapêutico , Talidomida/uso terapêutico , Adulto , Síndrome de Behçet/complicações , Colite/tratamento farmacológico , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Masculino
9.
Eur J Endocrinol ; 134(6): 737-40, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8766945

RESUMO

Pituitary apoplexy as a complication of cerebral angiography has been described in only a few case reports. Some studies have reported the clinical resolution of active acromegaly after pituitary apoplexy. We present a patient with active acromegaly due to a growth hormone (GH)-secreting pituitary macroadenoma, who developed anterior and posterior pituitary insufficiency following cerebral angiography. Furthermore, a significant reduction in tumour size was accompanied by normalization of mean 24 h in GH insulin-like growth factor I (IGF-I) and IGF binding protein 3 levels.


Assuntos
Acromegalia/fisiopatologia , Angiografia Cerebral/efeitos adversos , Transtornos Cerebrovasculares/etiologia , Doenças da Hipófise/etiologia , Acromegalia/diagnóstico , Adulto , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças da Hipófise/diagnóstico
10.
Digestion ; 57 Suppl 1: 36-7, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8813465

RESUMO

8 patients with papillary cancer (4 with metastases, 4 in remission), 7 follicular cancer patients (6 with metastases), 2 patients with anaplastic thyroid cancer and 4 other non-medullary thyroid cancer patients all received an intravenous bolus injection of 220 MBq [111In-DTPA-D-Phe1]octreotide. Planar anterior and posterior gamma camera images of head-neck, chest and abdomen were obtained 24 and 48 h after injection. All primary cancers showed [111In-DTPA-D-Phe1] octreotide uptake; none occurred in patients in remission. The results were compared with conventional radio-iodine scintigraphy in patients with metastasised, differentiated thyroid cancer.


Assuntos
Carcinoma Papilar, Variante Folicular/diagnóstico por imagem , Carcinoma Papilar, Variante Folicular/metabolismo , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/metabolismo , Receptores de Somatostatina/metabolismo , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/metabolismo , Humanos , Radioisótopos de Índio , Metástase Neoplásica/diagnóstico , Octreotida/análogos & derivados , Ácido Pentético/análogos & derivados , Cintilografia , Térbio
11.
Digestion ; 57 Suppl 1: 57-61, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8813472

RESUMO

Peptide receptor scintigraphy is more sensitive at the biological than anatomical level, in contrast to conventional imaging, which it complements. Neuroendocrine tumours have the most somatostatin receptors in vitro and their metastases are somatostatin receptor positive in vitro, so that [111In-DTPA-D-Phe1]octreotide (OCT) can be used to image them. OCT was compared with conventional imaging techniques (CON) in a European Multicentre Trial. In 350 evaluable patients, CON detected 88%, and OCT 80% (glucagonomas 100%, VIPomas 88%, carcinoids 87%, non-functioning islet cell tumours 82%, insulinomas 46%) of tumour sites but there was no systematic use of abdominal single-photon-emission computerised tomography. OCT demonstrated multiple tumour sites in 62 of 178 patients in whom CON had found only 1 lesion, with 60% confirmed. 12/16 lesions detected by OCT in 11 patients with no lesions according to CON were also confirmed. The impact of OCT on management was evaluated in 235 patients and affected 40%: it determined 29 surgical decisions, led to octreotide therapy in 47, and modified octreotide dose in 18. Six end-stage patients with neuroendocrine tumours were treated with OCT radionuclide therapy (up to a cumulative dose of 53 GBq per patient) in a phase I trial. There were no major side-effects after up to 2 years treatment, with impressive effects on hormone production and a likely anti-proliferative effect.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/radioterapia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/radioterapia , Receptores de Somatostatina/metabolismo , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/radioterapia , Humanos , Radioisótopos de Índio , Octreotida/análogos & derivados , Ácido Pentético/análogos & derivados , Cintilografia
13.
J Clin Endocrinol Metab ; 79(6): 1845-51, 1994 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7989493

RESUMO

Visualization of malignant lymphomas and granulomatous disease is possible by [111In-DTPA-D-Phe1]octreotide scintigraphy through binding of the radioligand to somatostatin receptors on activated leukocytes. Because thyroidal and orbital tissues are infiltrated by activated leukocytes in Graves' disease, a cross-sectional study to visualize disease activity with [111In-DTPA-D-Phe1]octreotide scintigraphy was performed. A correlation between thyroidal [111In-DTPA-D-Phe1]octreotide accumulation and free T4 (disease expression) and thyroid binding-inhibiting immunoglobulins (disease activity) is present in untreated hyperthyroid Graves' disease. There is also a correlation between orbital [111In-DTPA-D-Phe1]octreotide uptake and the clinical activity score (disease activity) and total eye score (disease expression), respectively, in Graves' orbitopathy. Visualization of thyroidal and orbital Graves' disease is feasible, but further investigation is necessary to establish the role of [111In-DTPA-D-Phe1]octreotide scintigraphy in representing disease activity and expression and in predicting therapeutical outcome.


Assuntos
Oftalmopatias/diagnóstico por imagem , Olho/diagnóstico por imagem , Doença de Graves/diagnóstico por imagem , Radioisótopos de Índio , Octreotida/análogos & derivados , Ácido Pentético/análogos & derivados , Glândula Tireoide/diagnóstico por imagem , Olho/metabolismo , Oftalmopatias/etiologia , Oftalmopatias/terapia , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Humanos , Metimazol/uso terapêutico , Octreotida/farmacocinética , Ácido Pentético/farmacocinética , Cintilografia , Glândula Tireoide/metabolismo , Tiroxina/uso terapêutico
15.
Eur J Nucl Med ; 20(8): 716-31, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8404961

RESUMO

Various tumours, classically specified as either neuroendocrine or non-neuroendocrine, contain high numbers of somatostatin receptors, which enable in vivo localization of the primary tumour and its metastases by scintigraphy with the radiolabelled somatostatin analogue octreotide. In addition granulomas and autoimmune processes can be visualized because of local accumulation of somatostatin receptor-positive activated mononuclear leucocytes. In many instances a positive scintigram predicts a favourable response to treatment with octreotide. It is tempting to speculate that octreotide labelled with an appropriate radionuclide might be used in cancer therapy. The successful application of radiolabelled octreotide in scintigraphy indicates the possible usefulness of other radiolabelled peptides, either native peptides or derivatives of these, in, for example, nuclear oncology. The small size of these peptides, e.g. bombesin and substance P, is of the utmost importance for a relatively fast blood clearance, thus leading to low background radioactivity. In this way peptides are powerful alternatives to (fragments of) monoclonal antibodies, the application of which to scintigraphic localization of specific cell surface antigen-bearing tumours is plagued by slow blood clearance and, hence, high background levels.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Octreotida/análogos & derivados , Ácido Pentético/análogos & derivados , Receptores de Somatostatina/fisiologia , Humanos , Radioisótopos de Índio , Radioisótopos do Iodo , Países Baixos , Cintilografia
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