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1.
An Bras Dermatol ; 87(5): 767-71, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23044573

RESUMO

Mucormycosis is an uncommon fungal infection caused by Mucorales. It frequently occurs in patients with neutropenia, diabetes, malignancy and on corticoid therapy. However, it is rare in patients with AIDS. Clinical disease can be manifested in several forms. The case reported illustrates the rare occurrence of chromoblastomycosis and mucormycosis in an immunosuppressed patient with multibacillary leprosy, under prolonged corticosteroid and thalidomide therapy to control leprosy type 2 reaction. Neutrophil dysfunction, thalidomide therapy and work activities are some of the risk factors in this case. Chromoblastomycosis was treated by surgical excision and mucormycosis with amphotericin B. Although the prognosis of mucormycosis is generally poor, in the reported case the patient recovered successfully. This case should alert dermatologists to possible opportunistic infections in immunosuppressed patients.


Assuntos
Cromoblastomicose/imunologia , Hospedeiro Imunocomprometido/imunologia , Hanseníase Multibacilar/tratamento farmacológico , Mucormicose/imunologia , Adulto , Cromoblastomicose/patologia , Glucocorticoides/administração & dosagem , Glucocorticoides/imunologia , Humanos , Hansenostáticos/administração & dosagem , Hansenostáticos/imunologia , Masculino , Mucormicose/patologia , Prednisona/administração & dosagem , Prednisona/imunologia , Talidomida/administração & dosagem , Talidomida/imunologia
2.
An. bras. dermatol ; 87(5): 767-771, Sept-Oct. 2012. ilus
Artigo em Inglês | LILACS | ID: lil-651573

RESUMO

Mucormycosis is an uncommon fungal infection caused by Mucorales. It frequently occurs in patients with neutropenia, diabetes, malignancy and on corticoid therapy. However, it is rare in patients with AIDS. Clinical disease can be manifested in several forms. The case reported illustrates the rare occurrence of chromoblastomycosis and mucormycosis in an immunosuppressed patient with multibacillary leprosy, under prolonged corticosteroid and thalidomide therapy to control leprosy type 2 reaction. Neutrophil dysfunction, thalidomide therapy and work activities are some of the risk factors in this case. Chromoblastomycosis was treated by surgical excision and mucormycosis with amphotericin B. Although the prognosis of mucormycosis is generally poor, in the reported case the patient recovered successfully. This case should alert dermatologists to possible opportunistic infections in immunosuppressed patients.


Mucormicose é uma infecção fúngica incomum causada por Mucorales. Ocorre frequentemente em pacientes com neutropenia, diabetes, corticoterapia e condições malignas. Porém, é rara em pacientes com AIDS. A doença pode apresentar-se em diferentes formas. Este caso ilustra a rara ocorrência de mucormicose e cromoblastomicose em um paciente com hanseníase multibacilar, que estava sendo tratado com prednisona e talidomida devido a eritema nodoso (reação hansênica tipo II). Disfunção de neutrófilos, uso de talidomida e atividades profissionais são alguns fatores de risco neste caso. A cromoblastomicose foi tratada por excisão cirúrgica e a mucormicose com anfotericina B. Embora o prognóstico da mucormicose seja ruim, neste caso o tratamento foi bem sucedido. Este caso alerta dermatologistas para a possibilidade de infecções oportunistas em pacientes imunossuprimidos.


Assuntos
Adulto , Humanos , Masculino , Cromoblastomicose/imunologia , Hospedeiro Imunocomprometido/imunologia , Hanseníase Multibacilar/tratamento farmacológico , Mucormicose/imunologia , Cromoblastomicose/patologia , Glucocorticoides/administração & dosagem , Glucocorticoides/imunologia , Hansenostáticos/administração & dosagem , Hansenostáticos/imunologia , Mucormicose/patologia , Prednisona/administração & dosagem , Prednisona/imunologia , Talidomida/administração & dosagem , Talidomida/imunologia
3.
Clin Immunol ; 102(3): 225-36, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11890709

RESUMO

Sarcoidosis, a chronic granulomatous disease of unknown etiology, is treated with immune suppressive drugs such as corticosteroids. Sarcoidosis patients have been reported to benefit clinically from treatment with thalidomide. We administered thalidomide for 16 weeks to eight patients with chronic skin sarcoidosis and evaluated the drug's effects before and with treatment. After thalidomide treatment, all skin biopsies showed decreases in granuloma size and reduction in epidermal thickness. We also observed extensive T cell recruitment into the granulomas, the appearance of multinucleated giant cells, and increased numbers of dermal Langerhans cells (CD1a(+)) and mature dendritic cells (CD83(+) or DC-LAMP(+)). Plasma IL-12 levels increased and remained elevated during the treatment period. We noted increased HLA-DR expression on peripheral blood lymphocytes and a corresponding drop in the naive T cell marker CD45RA. Our data suggest that thalidomide treatment of sarcoidosis results in granuloma differentiation to a Th1-type cellular immune response usually associated with protective immunity to tuberculosis and tuberculoid leprosy.


Assuntos
Fármacos Dermatológicos/imunologia , Fármacos Dermatológicos/uso terapêutico , Imunossupressores/uso terapêutico , Sarcoidose/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Talidomida/imunologia , Talidomida/uso terapêutico , Adulto , Antígenos CD/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Feminino , Citometria de Fluxo , Antígenos HLA-DR/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Interleucina-12/sangue , Interleucina-2/sangue , Células de Langerhans/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Sarcoidose/imunologia , Sarcoidose/patologia , Dermatopatias/imunologia , Dermatopatias/patologia , Linfócitos T/efeitos dos fármacos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/efeitos dos fármacos
4.
Crit Rev Immunol ; 22(5-6): 425-37, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12803319

RESUMO

Thalidomide has recently shown considerable promise in the treatment of a number of conditions, such as leprosy and cancer. Its effectiveness in the clinic has been ascribed to wide-ranging properties, including anti-TNF-alpha, T-cell costimulatory and antiangiogenic activity. Novel compounds with improved immunomodulatory activity and side effect profiles are also being evaluated. These include selective cytokine inhibitory drugs (SelCIDs), with greatly improved TNF-alpha inhibitory activity, and immunomodulatory drugs (IMiDs) that are structural analogs of thalidomide, with improved properties. A third group recently identified within the SelCID group, with phosphodiesterase type 4-independent activity, is in the process of being characterized in laboratory studies. This review describes the emerging immunological properties of thalidomide, from a historical context to present-day clinical applications, most notably in multiple myeloma but also in other cancers, inflammatory disease, and HIV. We also describe the laboratory studies that have led to the characterization and development of SelCIDs and IMiDs into potentially clinically relevant drugs. Early trial data suggest that these novel immunomodulatory compounds may supercede thalidomide to become established therapies, particularly in certain cancers. Further evidence is required, however, to correlate the clinical efficacy of these compounds with their known immunomodulatory, antiangiogenic, and antitumor properties.


Assuntos
Adjuvantes Imunológicos , Inibidores da Angiogênese , Antivirais , Sistema Imunitário/efeitos dos fármacos , Talidomida , Adjuvantes Imunológicos/farmacologia , Inibidores da Angiogênese/imunologia , Inibidores da Angiogênese/farmacologia , Antivirais/imunologia , Antivirais/farmacologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Talidomida/análogos & derivados , Talidomida/imunologia , Talidomida/farmacologia
5.
s.l; s.n; 2002. 13 p. ilus, tab.
Não convencional em Inglês | SES-SP, HANSEN, SESSP-ILSLACERVO, SES-SP | ID: biblio-1241152

RESUMO

Thalidomide has recently shown considerable promise in the treatment of a number of conditions, such as leprosy and cancer. Its effectiveness in the clinic has been ascribed to wide-ranging properties, including anti-TNF-alpha, T-cell costimulatory and antiangiogenic activity. Novel compounds with improved immunomodulatory activity and side effect profiles are also being evaluated. These include selective cytokine inhibitory drugs (SelCIDs), with greatly improved TNF-alpha inhibitory activity, and immunomodulatory drugs (IMiDs) that are structural analogs of thalidomide, with improved properties. A third group recently identified within the SelCID group, with phosphodiesterase type 4-independent activity, is in the process of being characterized in laboratory studies. This review describes the emerging immunological properties of thalidomide, from a historical context to present-day clinical applications, most notably in multiple myeloma but also in other cancers, inflammatory disease, and HIV. We also describe the laboratory studies that have led to the characterization and development of SelCIDs and IMiDs into potentially clinically relevant drugs. Early trial data suggest that these novel immunomodulatory compounds may supercede thalidomide to become established therapies, particularly in certain cancers. Further evidence is required, however, to correlate the clinical efficacy of these compounds with their known immunomodulatory, antiangiogenic, and antitumor properties.


Assuntos
Humanos , Adjuvantes Imunológicos/farmacologia , Antivirais/farmacologia , Antivirais/imunologia , Infecções por HIV/imunologia , Infecções por HIV/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/imunologia , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Sistema Imunitário , Talidomida/análogos & derivados , Talidomida/farmacologia , Talidomida/imunologia
7.
Saúde Soc ; 10(1): 55-64, jan.-jun. 2001.
Artigo em Português | LILACS | ID: lil-291217

RESUMO

A pesquisa teve por objetivo, compreender e avaliar os estados reacionais de pacientes portadores de hanseníase e o tratamento das reações. O método de abordagem do estudo foi indutivo, tendo como base o referencial bibliográfico, tomou-se como fonte de dados os prontuários dos portadores de hanseníase, disponíveis no Programa de Controle de Hanseníase da Secretaria Municipal de Saúde de Itajaí. Através do trabalho com os 78 pacientes inscritos no programa, observou-se que: 60,3 por cento tem de 15-49 anos; 65,4 por cento são do sexo masculino; 70,5 por cento manifestam a forma Virchowiana da doença; 60,3 por cento apresentaram estados reacionais durante tratamento; metade destes aproximadamente apresentaram quadro clínico de neurite, tendo sido tratados com prednisona. Também foram observados outros sintomas clínicos como o eritema nodoso hansênico, e o tratamento de escolha, sempre que possível foi a talidomida. A avaliação dos estados reacionais indica que, mais da metade dos portadores em tratamento, apresentam esta manifestação imunológica. É julgada pela literatura como consequência da doença e possível reação ao esquema poliquimioterápico


Assuntos
Humanos , Masculino , Feminino , Criança , Adulto , Hanseníase/tratamento farmacológico , Avaliação de Processos e Resultados em Cuidados de Saúde , Programas Médicos Regionais , Resultado do Tratamento , Anticorpos Antibacterianos , Clofazimina/imunologia , Dapsona/imunologia , Relação Dose-Resposta Imunológica , Registros Médicos , Mycobacterium leprae/imunologia , Rifampina/imunologia , Talidomida/imunologia
8.
Joint Bone Spine ; 68(6): 582-7, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11809002

RESUMO

Thalidomide, which was developed as a nonbarbiturate sedative agent, was taken off the market in 1961 after it was linked to a spate of major birth defects. Gradually, thalidomide was reintroduced for the treatment of a few skin diseases including leprous erythema nodosum, severe mucosal ulcers (e.g., associated with HIV infection or Behçet's disease), lymphocytic skin infiltrations, cutaneous lupus erythematosus, and chronic graft-versus-host disease. Recent reports of original pharmacological properties including modulation of cytokine production (mainly reduced TNF-alpha production) and inhibition of angiogenesis have led to the suggestion that thalidomide may be useful in some inflammatory and neoplastic conditions. Several open-label studies and case reports have described the effects of thalidomide in Crohn's disease, rheumatoid arthritis, ankylosing spondylarthritis, systemic sclerosis, and a few other systemic disorders. In these indications, minor but dose-limiting side effects were apparently common. Thalidomide analogs with better acceptability profiles are under evaluation. The anti-angiogenic effects of thalidomide may make this compound valuable as single-drug therapy or as an adjunct to chemotherapy in patients with cancer, particularly those with metastases or multiple myeloma. This possibility requires further evaluation.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização Patológica/tratamento farmacológico , Talidomida/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Inibidores da Angiogênese/imunologia , Humanos , Mieloma Múltiplo/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Neovascularização Patológica/imunologia , Talidomida/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo
10.
Am J Med ; 108(6): 487-95, 2000 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-10781782

RESUMO

More than three decades after its withdrawal from the world marketplace, thalidomide is attracting growing interest because of its reported immunomodulatory and anti-inflammatory properties. Current evidence indicates that thalidomide reduces the activity of the inflammatory cytokine tumor necrosis factor (TNF)-alpha by accelerating the degradation of its messenger RNA. Thalidomide also inhibits angiogenesis. Recently, the drug was approved for sale in the United States for the treatment of erythema nodosum leprosum, an inflammatory complication of Hansen's disease. However, it has long been used successfully in several other dermatologic disorders, including aphthous stomatitis, Behçet's syndrome, chronic cutaneous systemic lupus erythematosus, and graft-versus-host disease, the apparent shared characteristic of which is immune dysregulation. Many recent studies have evaluated thalidomide in patients with human immunodeficiency virus (HIV) infection; the drug is efficacious against oral aphthous ulcers, HIV-associated wasting syndrome, HIV-related diarrhea, and Kaposi's sarcoma. To prevent teratogenicity, a comprehensive program has been established to control access to the drug, including registration of prescribing physicians, dispensing pharmacies, and patients; mandatory informed consent and education procedures; and limitation of the quantity of drug dispensed. Clinical and, in some patients, electrophysiologic monitoring for peripheral neuropathy is indicated with thalidomide therapy. Other adverse effects include sedation and constipation. With appropriate safeguards, thalidomide may benefit patients with a broad variety of disorders for which existing treatments are inadequate.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Imunossupressores/uso terapêutico , Talidomida/uso terapêutico , Inibidores da Angiogênese/imunologia , Inibidores da Angiogênese/farmacologia , Fármacos Anti-HIV/imunologia , Fármacos Anti-HIV/farmacologia , Artrite Reumatoide/tratamento farmacológico , Síndrome de Behçet/tratamento farmacológico , Fármacos Dermatológicos/imunologia , Fármacos Dermatológicos/farmacologia , Ectromelia/induzido quimicamente , Eritema Nodoso/tratamento farmacológico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Humanos , Imunossupressores/imunologia , Imunossupressores/farmacologia , Hansenostáticos/imunologia , Hansenostáticos/farmacologia , Hansenostáticos/uso terapêutico , Hanseníase Virchowiana/tratamento farmacológico , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Neoplasias/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estomatite Aftosa/tratamento farmacológico , Teratógenos , Talidomida/imunologia , Talidomida/farmacologia
12.
Scand J Immunol ; 48(4): 397-402, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9790310

RESUMO

Thalidomide is reported to have immunomodulatory and anti-inflammatory effects, which have led to its use in the treatment of a number of immune-mediated disorders, including leprosy, discoid lupus and Behcet's disease, and to prevent immunological rejection phenomena following skin and bone marrow grafts. Experimental autoimmune neuritis (EAN) is a CD4+ T-cell-mediated demyelinating autoimmune disease, which represents an animal model for the study of the immunopathogenesis and immunotherapy of Guillain-Barré syndrome (GBS) in humans. We examined the effect of thalidomide in Lewis rats with EAN, which was induced by immunization with bovine peripheral nerve myelin (BPM) and complete Freund's adjuvant (CFA). Thalidomide prolonged clinical EAN when given at a dose of 200 mg/kg/day by gavage. This clinical effect was associated with increased numbers of inflammatory cells in sciatic nerve sections and elevated numbers of interferon-gamma (IFN-gamma) mRNA-expressing cells among lymph node mononuclear cells from thalidomide-treated EAN rats on day 17 postimmunization, i.e. at the peak of clinical EAN. The finding that thalidomide prolongs clinical EAN is in agreement with the clinical polyneuropathy reported in patients receiving treatment with thalidomide and limits its clinical usefulness.


Assuntos
Imunossupressores/imunologia , Imunossupressores/farmacologia , Neurite Autoimune Experimental/imunologia , Talidomida/imunologia , Talidomida/farmacologia , Animais , Bovinos , Interferon gama/imunologia , Bainha de Mielina/imunologia , Neurite Autoimune Experimental/induzido quimicamente , Ratos , Ratos Endogâmicos Lew
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