RESUMO
Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is a rare cause of lymphadenopathy in children. This benign disease can mimic lymphoma and misleads doctors. It was first described in Asia, where it occurred especially in young women. Recent publications show that it can also affect teenagers and young adults in Caucasian populations. The pathophysiology remains unknown. Three hypotheses have been raised for this disease: the role of viruses (in particular HHV-8), genetic predisposition (two alleles in HLA class II genes were found more frequently in patients with Kikuchi disease), and an autoimmune cause because of the correlation with lupus erythematosus. Few cases have been reported in Europe so far. In this article, we report three cases of Kikuchi disease observed in less than 2 months in a single hospital in France. All three patients were teenagers who presented with lymphadenopathy, either isolated or combined with fever, weakness, and weight loss. In all of them, the hypermetabolic activity of the lymph node on the PET scanner misled us to suspect lymphoma. The diagnosis of Kikuchi disease was finally made, for all patients, after 2 weeks in the hospital based on lymph node biopsy. Based on this report, we highlight that early biopsy in presence of lymphadenopathy can avoid unnecessary extensive investigations. Moreover, in this rare disease, it is very surprising to come across three cases that are not family-related, in such a short period of time. This strengthens the hypothesis of the possible implication of an environmental factor in the pathophysiology of Kikuchi disease.
Assuntos
Linfadenite Histiocítica Necrosante/diagnóstico , Linfoma/diagnóstico , Adolescente , Biópsia , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Linfadenite Histiocítica Necrosante/patologia , Humanos , Linfonodos/patologia , Linfadenopatia/etiologia , Linfadenopatia/patologia , Linfoma/patologia , Masculino , Tomografia por Emissão de PósitronsAssuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco de Sangue Periférico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Aloenxertos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare the efficacy of monthly administrations of the luteinizing hormone-releasing hormone agonists triptorelin pamoate and leuprolide acetate to induce and maintain castrate levels of serum testosterone in men with advanced prostate cancer. PATIENTS AND METHODS: Men with advanced prostate cancer were randomly assigned to receive triptorelin 3.75 mg or leuprolide 7.5 mg. The agent was injected intramuscularly every 28 days for nine injections. Primary endpoints were the percentages of men whose serum testosterone concentrations declined to and were maintained at or below castrate levels (= 1.735 nmol/L or = 500 ng/L) during 9 months (253 days) of treatment. Secondary endpoints were luteinizing hormone levels, bone pain, prostate specific antigen levels, quality of life, testosterone pharmacodynamics, survival, and safety variables. RESULTS: In all, 284 men received either triptorelin (140) or leuprolide (144). The percentage of men with castrate levels of serum testosterone was lower at 29 days for triptorelin than for leuprolide (91.2% vs 99.3%; point estimate - 8.0, 95% confidence interval - 16.9% to - 1.4%), but equivalent at 57 days (97.7% vs 97.1%). The mean (98.8% vs 97.3%) and cumulative (96.2% vs 91.2%) castration maintenance rates between 29 and 253 days were equivalent between the treatment groups. Secondary endpoints were equivalent between treatment groups except for the 9-month survival rate, which was significantly higher for triptorelin than for leuprolide (97.0% vs 90.5%; P = 0.033). Both treatments were well tolerated. CONCLUSION: Triptorelin reduced testosterone concentrations less rapidly, but maintained castration as effectively as leuprolide. There was no evidence that the slower onset of castration caused deleterious effects.
Assuntos
Antineoplásicos Hormonais/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Leuprolida/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Testosterona/sangue , Pamoato de Triptorrelina/análogos & derivados , Pamoato de Triptorrelina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Analgésicos/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Castração/métodos , Humanos , Leuprolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/sangue , Análise de Sobrevida , Resultado do Tratamento , Pamoato de Triptorrelina/efeitos adversosRESUMO
The activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to inhibit the production and the effects of proinflammatory cytokines. Since interleukin-1beta (IL-1beta) directly mediates cartilage degradation in osteoarthritis, we investigated the capability of PPARgamma ligands to modulate IL-1beta effects on human chondrocytes. RT-PCR and Western blot analysis revealed that PPARgamma expression was decreased by IL-1beta. 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), in contrast to troglitazone, was highly potent to counteract IL-1beta-induced cyclooxygenase-2 and inductible nitric oxide synthase expression, NO production and the decrease in proteoglycan synthesis. Western blot and gel-shift analyses demonstrated that 15d-PGJ2 inhibited NF-kappaB activation, while troglitazone was ineffective. Although 15d-PGJ2 attenuated activator protein-1 binding on the DNA, it potentiated c-jun migration in the nucleus. The absence or the low effect of troglitazone suggests that 15d-PGJ2 action in human chondrocytes is mainly PPARgamma-independent.
Assuntos
Condrócitos/efeitos dos fármacos , Cromanos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1/farmacologia , NF-kappa B/metabolismo , Prostaglandina D2/farmacologia , Tiazóis/farmacologia , Tiazolidinedionas , Fator de Transcrição AP-1/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Western Blotting , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Ciclo-Oxigenase 2 , DNA/genética , DNA/metabolismo , Indução Enzimática/efeitos dos fármacos , Humanos , Interleucina-1/antagonistas & inibidores , Isoenzimas/genética , Ligantes , Proteínas de Membrana , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , Prostaglandina D2/análogos & derivados , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandinas/biossíntese , Ligação Proteica/efeitos dos fármacos , Proteoglicanas/biossíntese , Proteínas Proto-Oncogênicas c-jun/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , TroglitazonaRESUMO
Despite a relatively low incidence of serious side effects, fluoroquinolones and the fluoroquinolone pefloxacin have been reported to occasionally promote tendinopathy that might result in the complication of spontaneous rupture of tendons. In the present study, we investigated in rodents the intrinsic deleterious effect of pefloxacin (400 mg/kg of body weight) on Achilles tendon proteoglycans and collagen. Proteoglycan synthesis was determined by measurement of in vivo and ex vivo radiosulfate incorporation in mice. Collagen oxidative modifications were measured by carbonyl derivative detection by Western blotting. An experimental model of tendinous ischemia (2 h) and reperfusion (3 days) was achieved in rats. Biphasic changes in proteoglycan synthesis were observed after a single administration of pefloxacin, consisting of an early inhibition followed by a repair-like phase. The depletion phase was accompanied by a marked decrease in the endogenous serum sulfate level and a concomitant increase in the level of sulfate excretion in urine. Studies of ex vivo proteoglycan synthesis confirmed the in vivo results that were obtained. The decrease in proteoglycan anabolism seemed to be a direct effect of pefloxacin on tissue metabolism rather than a consequence of the low concentration of sulfate. Pefloxacin treatment for several days induced oxidative damage of type I collagen, with the alterations being identical to those observed in the experimental tendinous ischemia and reperfusion model. Oxidative damage was prevented by coadministration of N-acetylcysteine (150 mg/kg) to the mice. These results provide the first experimental evidence of a pefloxacin-induced oxidative stress in the Achilles tendon that altered proteoglycan anabolism and oxidized collagen.