RESUMO
OBJECTIVE: Neuromyelitis optica (NMO) is a very severe autoimmune disorder of the central nervous system. It affects young subjects and has a poor prognosis both on a functional and vital level. Therefore, it is imperative to reduce the frequency of relapses. The purpose of this study was to evaluate the clinical and neuroradiological effectiveness of rituximab (RTX) on active forms of NMO. METHODS: We conducted a 2-year open prospective multicenter study that included 32 patients treated with RTX at a dose of 375 mg/m2/week for 1 month. When the number of circulating CD19+ B cells reached 1%, a maintenance therapy was started, consisting of two infusions of 1 g of RTX, administered at a 15-day interval. The primary objective was to reduce the annual relapse rate (ARR), in comparison to that observed in the 2 years before treatment onset. RESULTS: Rituximab administration reduced the ARR from 1.34 to 0.56 (p = 0.0005). The average Expanded Disability Status Scale (EDSS) score significantly improved by 1.1 point, from 5.9 (2-9) to 4.8 (0-9) after 2 years (p = 0.03). Anti-aquaporin-4 antibodies' level predicted treatment failure (p = 0.03). Frequency of Gad+ lesions in spinal cord decreased from 23.3 to 14.2%. RTX treatment did not prevent the death of three patients (treatment failure in two patients and acute myeloid leukemia in a patient previously treated with mitoxantrone). CONCLUSION: Rituximab is clinically effective in active forms of NMO, although few patients are resistant to the treatment.
Assuntos
Fatores Imunológicos/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Rituximab/uso terapêutico , Resultado do Tratamento , Adolescente , Adulto , Anticorpos/sangue , Aquaporina 4/genética , Aquaporina 4/imunologia , Avaliação da Deficiência , Feminino , Gadolínio/farmacocinética , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/sangue , Neuromielite Óptica/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: The severity of envenoming from Bothrops lanceolatus is determined by the development of cerebral, myocardial or pulmonary infarctions, and occasionnaly by serious local envenoming. Introduction of specific antivenom has resulted in a dramatic improvement in the prognosis of this envenoming. Against this background, we report 3 recent cases of patients bitten by B. lanceolatus who developed cerebral infarctions despite early administration of antivenom. METHODS: In 1991 a protocol was designed to apply the same evaluation and treatment to all envenomed patients. The clinical results have been continuously monitored. RESULTS: Between April 1993 and July 2003, 128 envenomed patients (age 6-83 (mean 45) years) were treated. No coagulopathy, thrombotic complication or death occurred in patients who were given early antivenom therapy--up to 6h following the bite--and 126 patients recovered. Between August 2003 and October 2004, 10 additional patients (18-66 (mean 46) years) were given antivenom at the time of admission at hospital. Of these, 3 developed cerebral infarctions within 24h. Effectiveness of antivenom was tested on mouse, and found to be lower than specified by the manufacturer. DISCUSSION: Our data shows that recently the antivenom may have lost some of its efficacy. Possible mechanisms include variability in venom composition or loss of activity of the antibodies produced more than 15 years ago. The question is whether we should attempt to produce improved antivenom. This could include activity against the venom of Bothrops caribbaeus from the neighbouring island of St Lucia, which shares a monophyletic group with B. lanceolatus and whose venom produces a similar thrombotic syndrome. CONCLUSION: Prevention of systemic vessels thrombosis remains the main therapeutic challenge of B. lanceolatus envenoming in Martinique.
Assuntos
Bothrops , Trombose Intracraniana/etiologia , Mordeduras de Serpentes/complicações , Acidente Vascular Cerebral/etiologia , Adolescente , Adulto , Idoso , Animais , Antivenenos/uso terapêutico , Criança , Humanos , Pessoa de Meia-Idade , Mordeduras de Serpentes/terapiaRESUMO
A registry of hematological malignancies is held in the unit of cytology of the University Hospital of Martinique. Human T cell lymphotropic virus type-1 (HTLV1) is endemic in this island. We determined the incidence and epidemiological features of hematological malignancies from the 715 new cases diagnosed between 1990 and 1998 among the adult population. Incidence rates per year were steady during this period. The most frequent hematological malignancies were multiple myeloma (MM) (34%), followed by non-Hodgkin's lymphoma (NHL) (23%). Among the cases of NHL with an immunohistological study, 57% had a T cell phenotype. Among these 61% were adult T cell leukemia/lymphoma. Epidemiological data on hematological malignancies in the West Indies has not been previously reported. There are two striking differences with other population-based registries: a high incidence of MM (5/100000) and a high proportion of T cell NHL among NHL (57%). The high proportion of T cell NHL is probably due to the high incidence of ATL. A low incidence of B cell NHL might also contribute to this effect. The increased incidence of MM in West Indies had not been previously reported. A similar high incidence of MM has been reported among Afro-Americans in the USA.
Assuntos
Leucemia-Linfoma de Células T do Adulto/epidemiologia , Linfoma não Hodgkin/epidemiologia , Mieloma Múltiplo/epidemiologia , Adulto , Idoso , População Negra , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Índias Ocidentais/epidemiologiaRESUMO
A clinicopathologic study was conducted to assess the implication of HTLV-I infection, Strongyloides stercoralis (Ss) infection, and P53 overexpression in the development, response to treatment, and evolution of non-Hodgkin's lymphoma (NHL) in Martinique, French West Indies. Two groups of patients, with 22 and 41 participants with B-cell and T-cell lymphoma, respectively, were analyzed. HTLV-I antibodies were detected in 24 (59%) patients with T-cell lymphoma of whom 19 (46%) fulfilled diagnostic criteria of adult T-cell leukemia/lymphoma (ATLL). By comparison with other T-cell lymphomas, patients with ATLL were significantly younger (52 versus 63 years; p = .03), had a significantly higher incidence of hypercalcemia (60% versus 0%; p = .0001), a trend for higher incidence of digestive tract localization (21% versus 4%; p = .1) and significantly shorter median survival (6 versus 17 months; p = .03). Similar results were observed when all 24 HTLV-I-infected patients with T-cell lymphoma were compared with the 17 seronegative patients. Strongyloidiasis was diagnosed in 11 of 34 patients tested for Ss infection. All 4 Ss-infected (Ss-positive) ATLL patients treated with combination chemotherapy achieved complete remission (CR) versus only 2 of 7 Ss-negative ATLL patients (p = .04). In addition, survival of Ss-positive patients with ATLL was better than that of the uninfected patients: 27 versus 5 months, p = .04, respectively). P53 expression was assessed by immunohistochemistry on lymph node biopsies from 37 patients including 18 B-cell lymphomas, 14 ATLL, and 5 other T-cell lymphomas. P53 overexpression (P53-positive) was observed in 6 samples that corresponded in all 6 patients with ATLL. All P53-positive ATLL patients had stage IV disease with elevated lactate dehydrogenase (LDH) levels. By comparison with other ATLL patients studied for p53 expression, P53-positive ATLL were characterized by a lower response rate to combination chemotherapy (CR: 0 of 6 versus 4 of 6; p = .04) and a shorter survival (2 versus 9 months, p = .04). Our results suggest that ATLL represents almost 50% of T-cell lymphomas in Martinique; Ss infection during ATLL seems to be linked with a high response rate to chemotherapy and prolonged survival; and P53 overexpression is observed in almost 50% of aggressive ATLL from Martinique and, even in advanced clinical subtypes, is associated with resistance to chemotherapy and short-term survival.
Assuntos
Doenças Endêmicas , Infecções por HTLV-I/complicações , Linfoma não Hodgkin/complicações , Strongyloides stercoralis , Estrongiloidíase/complicações , Proteína Supressora de Tumor p53/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Humanos , Leucemia-Linfoma de Células T do Adulto , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/terapia , Masculino , Martinica/epidemiologia , Pessoa de Meia-IdadeRESUMO
The correlation between clinical grading of patients bitten by Bothrops lanceolatus and the subsequent development of their envenoming was examined. Severity of envenoming was graded using a 1-4 scale (minor to major). Patients were classified into 2 groups according to the time elapsed between bite and treatment with a specific purified equine F(ab')2 antivenom. The late/no treatment group (n = 33) was characterized by a systemic thrombotic complication rate of 14/33 (42.4%) leading to 4 deaths, which increased with the maximum severity assessed on the first day following the bite (P = 0.003). However, infarctions could develop in patients who presented initially with signs of moderate envenoming, normal blood clotting and low serum levels of venom antigens. No such complication of fatality occurred in the early (0.5-6 h) treatment group (n = 70). Multiple regression analysis showed that duration of stay in hospital in this group increased with the length of the snake (P = 0.017), venom antigenaemia (P = 0.016), initial grading (P < 0.001), and with the need for surgical debridement (n = 10/70, P < 0.001). Outcome was correlated with initial severity of envenoming. However, the only factor with a positive prognostic significance for the individual envenomed patient was the early infusion of specific antivenom, which led to 100% recovery in our series.
Assuntos
Bothrops , Venenos de Crotalídeos/intoxicação , Mordeduras de Serpentes/classificação , Analgésicos/uso terapêutico , Animais , Antivenenos/uso terapêutico , Seguimentos , Humanos , Tempo de Internação , Martinica , Penicilinas/uso terapêutico , Prognóstico , Índice de Gravidade de Doença , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/terapia , Antitoxina Tetânica/uso terapêuticoRESUMO
Onset of adult T-cell leukemia (ATL) usually follows a long period of viral latency. Strongyloides stercoralis infection has been considered a cofactor of leukemogenesis. Hypereosinophilia (HE) is also observed and could be associated with either the presence of parasites or the leukemic process. In non-Hodgkin's lymphoma, eosinophilia may or may not affect prognosis. To determine whether infection with S stercoralis and therefore eosinophilia has a significant effect on the development of ATL, we studied two variables in 38 patients: age at onset and median survival rate. Infected (Ss+) patients (n = 19) were younger (P = .0002) and survived longer (P = .0006) than uninfected (Ss-) patients (n = 19) (median age, 39 vs 70 years; median survival, 167 vs 30 days). Mean survival of patients with hypereosinophilia (HE+) was not significantly different from that of patients without hypereosinophilia (HE-) (P = .57). However, overall survival was longer for Ss + HE + patients than for Ss-HE-patients (P = .01; 180 vs 30 days) or Ss-HE + patients (P = .03; 180 vs 45 days). Among patients with mean survival more than 180 days, Ss + HE + patients survived longer (P = .028). Our data confirm that cofactors related to the environment, such as S stercoralis and hypereosinophilia associated with S stercoralis or human T-cell leukemia virus, type 1 (HTLV-1) might be important in HTLV-1-associated leukemogenesis and suggest that hypereosinophilia affects the prognosis of HTLV-1-associated leukemia.
Assuntos
Eosinofilia/parasitologia , Leucemia-Linfoma de Células T do Adulto/parasitologia , Strongyloides stercoralis , Estrongiloidíase/etiologia , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Animais , Eosinofilia/mortalidade , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/mortalidade , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Prognóstico , Estrongiloidíase/mortalidade , Taxa de SobrevidaRESUMO
The mechanisms of chronic infestation by Strongyloides stercoralis (Ss) are unknown. Immunodepression is classically evoked to explain the proliferation of the parasite that is sometimes massive and overwhelming. We present here two retrospective studies of 13 cases of strongyloidiasis (three disseminated strongyloidiasis) out of 26 patients with adult T-cell leukemia/lymphoma (ATL) and of ten cases of strongyloidiasis out of 98 patients with AIDS. Ten patients out of 98 were dually infected with both HIV and HTLV-1: 2/10 also infected by Ss. The frequency of Ss infection appears higher in ATL patients when compared with AIDS patients (P < 0.001). Ss-infected ATL patients were younger than those uninfected (P < 0.01). Ss-infected AIDS patients were older than the ones uninfected (p < 0.03). No significative difference was found between ATL and AIDS patients who were over 40 years-old. These data suggest that 1) the particular type of immunodepression produced early by HTLV-1 is more favorable to the development of Ss infection than the one associated with HIV, 2) the latency of expression of HTLV-1, prior to the development of leukemia, is reduced in Ss-infected patients, 3) Ss infection may slow down VIH pathogenic activity.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Leucemia-Linfoma de Células T do Adulto/complicações , Strongyloides stercoralis , Estrongiloidíase/etiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Infecções Oportunistas Relacionadas com a AIDS/fisiopatologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Portador Sadio , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Leucemia-Linfoma de Células T do Adulto/fisiopatologia , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Estrongiloidíase/epidemiologia , Estrongiloidíase/fisiopatologiaRESUMO
Envenomation by the Bothrops lanceolatus, a snake found only in Martinique, leads to swelling and pain, and occasionally to systemic signs and/or coagulopathy. Severe thromboses at some distance from the site of the bite may appear within 48 hr. Uncertainties as to the actual development of thrombotic complications in patients appearing to be suffering from moderate poisoning and as to the availability and the toxicity of a monospecific antivenom (AVS) initially led us to reserve antivenom for the most severe cases, and to use anticoagulants to prevent thromboses in all patients. This approach was modified after we observed serious thromboses in patients with moderate poisoning. Of 50 adult snake bite cases hospitalized between June 1991 and August 1994, 11 developed serious thrombotic complications at 36 /+- 27 hr (mean +/- SD) (range 12-96) following envenomation, despite early preventive anticoagulant therapy. Those included pulmonary embolism (two cases), cerebral infarction (six cases), myocardial infarction (one case), and cerebral and myocardial infarctions (two cases). Sixteen patients were not treated with AVS: 10 of these recovered without complications and six developed systemic thrombosis causing permanent disability in three cases. Thirty were treated with an intravenous infusion of 2-6 vials of AVS given 2-48 hr after the bite. Of these, three died of cerebral infarction that developed before the initiation of serotherapy. All others recovered. Among patients treated with AVS, three presented with mild anaphylactic reactions, while one developed serum sickness that responded to steroids. These data indicate that preventive anticoagulant therapy is of limited efficacy in Martinique.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Antivenenos/uso terapêutico , Bothrops , Nadroparina/uso terapêutico , Mordeduras de Serpentes/terapia , Trombose/prevenção & controle , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Coagulação Sanguínea , Quimioterapia Combinada , Feminino , Humanos , Masculino , Martinica , Pessoa de Meia-Idade , Mordeduras de Serpentes/complicaçõesRESUMO
Twenty-six cases of adult T-cell leukemia/lymphoma (ATLL) were identified between 1983 and 1991 in Martinique (French West Indies). There were 14 men and 12 women, all of mixed racial descent and born in Martinique. Their ages ranged from 23 to 95 years. The main clinical and laboratory features at initial presentation were peripheral lymphadenopathy (22 cases), hepatomegaly (11 cases), splenomegaly (10 cases), cutaneous lesions (12 cases), hypercalcemia (16 cases), refractory infection by Strongyloides stercoralis (12 cases), and pre-existing autoimmune disorders (4 cases). All patients had absolute lymphocytosis with circulating pleomorphic abnormal lymphocytes. The prognosis was poor, with most patients (20 cases) surviving for less than 6 months. Although the overall clinicopathologic features of ATLL in this series are similar to those described in previous reports, we observed three additional points of interest: a high association with Strongyloides infection, an increased incidence of tropical spastic paresis/HTLV-1 associated myelopathy (TSP/HAM) among the relatives of the patients (5 cases), and the presence of prior collagen vascular diseases.