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OBJECTIVE: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). METHODS: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. RESULTS: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2 ± 0.5 vs 1.7 ± 2.4 before the use of anti-TNF, p < 0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p < 0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR = 0.33 [0.12-0.89]; p = 0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. CONCLUSION: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).
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Anticorpos Monoclonais/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/metabolismo , Síndrome de Behçet/mortalidade , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Recidiva , Retratamento , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
PCR detection of Toxoplasma gondii in blood has been suggested as a possibly efficient method for the diagnosis of ocular toxoplasmosis (OT) and furthermore for genotyping the strain involved in the disease. To assess this hypothesis, we performed PCR with 121 peripheral blood samples from 104 patients showing clinical and/or biological evidence of ocular toxoplasmosis and from 284 (258 patients) controls. We tested 2 different extraction protocols, using either 200 µl (small volume) or 2 ml (large volume) of whole blood. Sensitivity was poor, i.e., 4.1% and 25% for the small- and large-volume extractions, respectively. In comparison, PCR with ocular samples yielded 35.9% sensitivity, while immunoblotting and calculation of the Goldmann-Witmer coefficient yielded 47.6% and 72.3% sensitivities, respectively. Performing these three methods together provided 89.4% sensitivity. Whatever the origin of the sample (ocular or blood), PCR provided higher sensitivity for immunocompromised patients than for their immunocompetent counterparts. Consequently, PCR detection of Toxoplasma gondii in blood samples cannot currently be considered a sufficient tool for the diagnosis of OT, and ocular sampling remains necessary for the biological diagnosis of OT.
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Sangue/parasitologia , DNA de Protozoário/isolamento & purificação , Olho/parasitologia , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Toxoplasma/isolamento & purificação , Toxoplasmose Ocular/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA de Protozoário/genética , Feminino , Humanos , Immunoblotting/métodos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Toxoplasma/genética , Adulto JovemRESUMO
BACKGROUND: Hypertension and oxidative stress are involved in the pathophysiological mechanism of stroke. We aimed to investigate the modification impact of the pro-oxidant-anti-oxidant balance (PAB) on the association between hypertension and stroke recurrence (SR). METHODS: A cross-sectional design was conducted from December 2019 to December 2020 in 951 stroke patients in six hospitals across Vietnam. Hypertension was defined using antihypertensive medication or systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. PAB was estimated using weighting methods based on smoking, drinking, and overweight/obesity with pro-oxidant capacity, diet quality, fruit intake, vegetable intake, and physical activity with antioxidant capacity. The higher PAB scores indicated a beneficial balance shifting toward antioxidant dominance. SR was diagnosed by neurologists. Moreover, sociodemographic and health conditions were included as covariates. Multiple logistic regression analyses were used to explore the associations and interactions. RESULTS: The hypertension and SR proportions were 72.8% and 17.5%, respectively. hypertension was associated with an increased SR likelihood (odds ratio (OR) = 1.93; p = 0.004), whereas a higher PAB score was associated with a lowered SR likelihood (OR = 0.87; p = 0.003). Moreover, hypertension interacting with every one-point increment of PAB was associated with a lowered SR likelihood (OR = 0.83; p = 0.022). CONCLUSIONS: The harmful impact of hypertension on SR could be alleviated by PAB. The interplay of health behaviors should be highlighted in the intervention strategies for stroke prevention.
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Hipertensão , Acidente Vascular Cerebral , Humanos , Antioxidantes , Espécies Reativas de Oxigênio , Estudos Transversais , Hipertensão/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Pressão SanguíneaRESUMO
Background: Comorbidity, along with aging, affects stroke-induced health-related quality of life (HRQoL). We examined the potential role of diet quality in modifying the association between comorbidity and HRQoL in patients with stroke. Methods: A cross-sectional study was conducted on 951 patients with stroke from December 2019 to December 2020 across Vietnam. Comorbidity was assessed using the Charlson Comorbidity Index (CCI) items and classified into two groups (none vs. one or more). Diet quality was evaluated using the Dietary Approaches to Stop Hypertension Quality (DASH-Q) questionnaire, and HRQoL was measured using the RAND-36, with a higher score indicating better diet quality or HRQoL, respectively. Besides, socio-demographics, health-related behaviors (e.g., physical activity, smoking, and drinking), disability (using WHODAS 2.0), and health literacy were also assessed. Linear regression analysis was utilized to explore the associations and interactions. Results: The proportion of patients with stroke aged ≥65 years and having comorbidity were 53.7 and 49.9%, respectively. The HRQoL scores were 44.4 ± 17.4. The diet quality was associated with higher HRQoL score (regression coefficient, B, 0.14; (95% confidence interval, 95% CI, 0.04, 0.23; p = 0.004), whereas comorbidity was associated with lower HRQoL score (B, -7.36; 95% CI, -9.50, -5.23; p < 0.001). In interaction analysis, compared to patients without comorbidity and having the lowest DASH-Q score, those with comorbidity and higher DASH-Q score had a higher HRQoL score (B, 0.21; 95% CI, 0.03, 0.39; p = 0.021). Conclusion: The findings showed that good diet quality could modify the adverse impact of comorbidity on HRQoL in patients with stroke. Diet quality should be considered as a strategic intervention to improve the HRQoL of patients with stroke, especially those with comorbidity, and to promote healthier aging.
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We report the direct genotyping analysis of Toxoplasma gondii in ocular samples collected from 20 patients, as well as associated clinical and epidemiological data. This work was aimed at better understanding the impact of genotypes of Toxoplasma gondii strains on toxoplasmic retinochoroiditis. For this purpose, we studied the aqueous humor (AH) or vitreous humor (VH) of 20 patients presenting with ocular toxoplasmosis (OT) in 2 hospitals in France. Genetic characterization was obtained with microsatellite markers in a multiplex PCR assay. In contrast to the results of previous studies, we found no association between atypical Toxoplasma gondii genotypes and the occurrence of OT. Considering the local epidemiological data, our OT patients seemed to be infected more frequently by ordinary type II strains found in the environment. In conclusion, direct genotyping of Toxoplasma gondii strains from aqueous or vitreous humor showed a predominance of the type II genotype in ocular toxoplasmosis; this may be due to a high exposure rate of this genotype in humans.
Assuntos
Humor Aquoso/parasitologia , Toxoplasma/classificação , Toxoplasma/genética , Toxoplasmose Ocular/parasitologia , Corpo Vítreo/parasitologia , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA de Protozoário/genética , Feminino , França/epidemiologia , Genótipo , Humanos , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Epidemiologia Molecular , Reação em Cadeia da Polimerase , Toxoplasma/isolamento & purificação , Adulto JovemRESUMO
BACKGROUND: Comorbidity is common and causes poor stroke outcomes. We aimed to examine the modifying impacts of physical activity (PA) and diet quality on the association between comorbidity and disability in stroke patients. METHODS: A cross-sectional study was conducted on 951 stable stroke patients in Vietnam from December 2019 to December 2020. The survey questionnaires were administered to assess patients' characteristics, clinical parameters (e.g., Charlson Comorbidity Index items), health-related behaviors (e.g., PA using the International Physical Activity Questionnaire- short version), health literacy, diet quality (using the Dietary Approaches to Stop Hypertension Quality (DASH-Q) questionnaire), and disability (using the World Health Organization Disability Assessment Schedule II (WHODAS II)). Linear regression models were used to analyze the associations and interactions. RESULTS: The proportion of comorbidity was 49.9% (475/951). The scores of DASH-Q and WHODAS II were 29.2 ± 11.8, 32.3 ± 13.5, respectively. Patients with comorbidity had a higher score of disability (regression coefficient, B, 8.24; 95% confidence interval, 95%CI, 6.66, 9.83; p < 0.001) as compared with those without comorbidity. Patients with comorbidity and higher tertiles of PA (B, -4.65 to -5.48; p < 0.05), and a higher DASH-Q score (B, -0.32; p < 0.001) had a lower disability score, as compared with those without comorbidity and the lowest tertile of PA, and the lowest score of DASH-Q, respectively. CONCLUSIONS: Physical activity and diet quality significantly modified the negative impact of comorbidity on disability in stroke patients. Strategic approaches are required to promote physical activity and healthy diet which further improve stroke rehabilitation outcomes.
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Dieta Saudável , Pessoas com Deficiência , Exercício Físico , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Letramento em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular Cerebral , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
We compared three biological methods for the diagnosis of ocular toxoplasmosis (OT). Paired aqueous humor and serum samples from 34 patients with OT and from 76 patients with other ocular disorders were analyzed by three methods: immunoblotting or Western blotting (WB), the calculation of the Goldmann-Witmer coefficient (GWC), and PCR. WB and GWC each revealed the intraocular production of specific anti-Toxoplasma immunoglobulin G in 81% of samples (30 of 37). PCR detected toxoplasmic DNA in 38% of samples (13 of 34). Nine of the 13 PCR-positive patients were immunocompetent. Combining the techniques significantly improved the diagnostic sensitivity, to 92% for the GWC-WB combination, 90% for the WB-PCR combination, and 93% for the GWC-PCR combination. The combination of all three techniques improved the sensitivity to 97%.
Assuntos
Humor Aquoso/imunologia , Humor Aquoso/parasitologia , Immunoblotting/métodos , Reação em Cadeia da Polimerase/métodos , Toxoplasmose Ocular/diagnóstico , Animais , Anticorpos Antiprotozoários/análise , Anticorpos Antiprotozoários/sangue , Especificidade de Anticorpos , DNA de Protozoário/análise , Humanos , Imunoglobulina G/análise , Imunoglobulina G/sangue , Sensibilidade e Especificidade , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasma/isolamento & purificação , Toxoplasmose Ocular/parasitologiaRESUMO
Immune-related adverse events (IRAEs) are rare but serious adverse events that may be associated with inhibitors of few immune control points. The purpose here is to report the case of an inflammatory ocular disease, potentially linked to the immunity and use of nivolumab, a new immunological agent used for the treatment of a solid tumor. In spite of the involvement of this treatment in the onset of inflammation, we must always seek another cause. It is possible to continue this treatment by considering the benefit/risk balance for each patient. Close collaboration between oncologists and ophthalmologists is necessary in the diagnosis and rapid management of these IRAE ocular related to these new emerging therapies.
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Antineoplásicos/efeitos adversos , Nivolumabe/efeitos adversos , Uveíte/induzido quimicamente , Carcinoma Broncogênico/tratamento farmacológico , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Uveíte/diagnósticoRESUMO
New anticancer therapies, immune pathway inhibitors, may cause immune-related adverse events (IRAE). Immune-related ocular toxicities are rare but are potentially serious adverse events. The purpose of this article is to report a case of ocular inflammatory involvement potentially related to the immune response and the use of nivolumab, a new immunologic agent used for the treatment of a solid tumor. Despite the implication of this therapy in the occurrence of inflammation, other causes must always be ruled out. It is possible to continue this therapy in consideration of the risk/benefit ratio for each patient. Close collaboration between oncologists and ophthalmologists is necessary in the diagnosis and timely management of IRAE related to these new emerging therapies.
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Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Imunossupressores/efeitos adversos , Uveíte Anterior/induzido quimicamente , Adenocarcinoma/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Infecções Oculares Virais/diagnóstico , Feminino , Granuloma/induzido quimicamente , Granuloma/tratamento farmacológico , Granuloma/imunologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Nivolumabe , Receptor de Morte Celular Programada 1/efeitos dos fármacos , Receptor de Morte Celular Programada 1/imunologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Uveíte Anterior/tratamento farmacológico , Uveíte Anterior/imunologiaRESUMO
PURPOSE: To compare the efficacy and safety of diclofenac sodium 0.1% eyedrops packaged in an Abak multidose container without preservative (Dicloabak) with the reference product, sodium merthiolate-preserved diclofenac sodium 0.1% eyedrops, in controlling postoperative inflammation after cataract surgery. METHODS: The multicenter, controlled, randomized, single-masked study included 194 patients (Dicloabak 96, preserved diclofenac 98) scheduled to have cataract surgery by phacoemulsification with foldable intraocular lens. All were evaluated preoperatively and postoperatively after 1, 7, and 28 days. Postoperative inflammation was measured by the total score of anterior chamber cells and flare. Ocular plin, conjunctival hyperemia and ciliary flush were also assessed. Postoperative patient assessments also included visual acuity, objective tolerance by slit-lamp, fluorescein test, and subjective evaluation of local tolerance. RESULTS: There was no statistically significant difference between the groups in the total score of flare and cells or the degree of conjunctival hyperemia and ciliary flush at any study visit. Dicloabak was demonstrated to be not inferior to preserved diclofenac at all assessment times. The overall assessment of local tolerance was similar for both study medications. CONCLUSIONS: Preservative suppression did not alter diclofenac efficacy. Results support the good safety profile of both formulations when dosed three times daily for 4 weeks in absence of concomitant use of drugs potentially toxic for cornea. Preservative-free formulations like Dicloabak should be preferred to generic diclofenac formulations including other ingredients and may improve the safety profile of this topical nonsteroid anti-inflammatory drug.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Diclofenaco/administração & dosagem , Facoemulsificação , Complicações Pós-Operatórias/prevenção & controle , Uveíte Anterior/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Câmara Anterior/patologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Diclofenaco/efeitos adversos , Feminino , Humanos , Inflamação/etiologia , Inflamação/patologia , Inflamação/prevenção & controle , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/efeitos adversos , Conservantes Farmacêuticos/administração & dosagem , Conservantes Farmacêuticos/efeitos adversos , Timerosal/administração & dosagem , Timerosal/efeitos adversos , Resultado do Tratamento , Uveíte Anterior/etiologia , Uveíte Anterior/patologia , Acuidade VisualRESUMO
PURPOSE: This study was designed to evaluate and compare the efficacy of early treatment of CRVO with either hemodilution by erythrocytopheresis or intravitreal (IVT) ranibizumab, or both. MATERIAL AND METHODS: A multicentric prospective randomized study including patients with CRVO for less than 1 month was designed. Patients were randomized into 3 treatment groups: hemodilution (HD group), 3 monthly intravitreal injections of ranibizumab followed by PRN treatment (IVT group), or combined treatment (IVT+HD group). A monthly evaluation during a 6-month follow-up included best-corrected visual acuity (BCVA) and macular thickness measurements with OCT. Fluorescein angiography was performed at baseline, month 2 and month 6. Local and systemic tolerability of the different treatments were also compared. RESULTS: Forty-four CRVO patients were included between February 2010 and June 2013: 20 in the IVT group, 13 in the HD group and 11 in the HD+IVT group. The mean duration of CRVO at baseline was 10 days and 16 days at the time of treatment without any significant difference between groups. Retinal ischemia was present at baseline in 40% of eyes in each group. After a 6-month follow-up, no difference between the 3 groups was observed in BCVA (10.5 ETDRS letters, 14.6 and 14.1 in the IVT group, HD group and IVT+HD group respectively, P=0.726) or in macular thickness (398 µ, 440 µ and 379 µ respectively, P=0.465). The time until treatment from CRVO onset, ranging from 1 to 35 days, was not correlated to final outcomes. No significant difference in the mean number of IVT (3.2 in the IVT+HD group vs 3.7 in the IVT group) was observed at 6 months. CONCLUSION: No difference in BCVA nor in macular thickness was seen at M6 between the study groups. The duration of CRVO at the time of the initiation of the treatment was not correlated to better visual outcomes. Therefore, etiologic treatment with HD can still be proposed as a first-line treatment in young patients, which allows delaying or avoiding the IVT treatment and its potential side effects. Anti-VEGF IVT still remains an effective option in every case and can be started one month after the beginning of the CRVO.
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Inibidores da Angiogênese/uso terapêutico , Hemodiluição , Ranibizumab/uso terapêutico , Oclusão da Veia Retiniana/terapia , Idoso , Terapia Combinada , Intervenção Médica Precoce , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
The systemic effect of three beta-blocking eyedrops was compared in a placebo-controlled, double-blind trial in 12 healthy male volunteers. Each subject received successively each treatment in random order at weekly intervals. The eyedrops administered were as follows: 0.5% timolol, 2% carteolol, 0.6% metipranolol, and placebo. We evaluated the intraocular pressure and systemic beta-blockade 3 hours after a single administration of one eyedrop in each eye. The systemic beta-blocking effect was evaluated by the isoproterenol sensitivity test, that is the dose of isoproterenol required to increase resting heart rate by 25 bpm (I25). Each beta-blocking eyedrop antagonized the chronotropic effect of isoproterenol. I25 for placebo was 3.1 +/- 0.5 micrograms, for metipranolol 5.2 +/- 0.9 micrograms (P less than 0.005), for timolol 10.9 +/- 1.9 micrograms (P less than 0.001), and for carteolol 39.6 +/- 5.4 micrograms (P less than 0.0005). Each treatment significantly decreased the intraocular pressure: metipranolol 3.6 +/- 0.4 mm Hg (P less than 0.001), timolol 2.44 +/- 0.4 mm Hg (P less than 0.01), and carteolol 2.38 +/- 0.48 mm Hg (P less than 0.01) compared with placebo. The resting heart rate and blood pressure were not influenced by the treatments. Even though the results might be different in the case of an earlier or a later time of evaluation or chronic administration, we believe that the isoproterenol sensitivity test may be used to evaluate the systemic effect of beta-blocking eyedrops.
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Antagonistas Adrenérgicos beta/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Isoproterenol/antagonistas & inibidores , Adulto , Pressão Sanguínea/efeitos dos fármacos , Carteolol/farmacologia , Método Duplo-Cego , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Metipranolol/farmacologia , Soluções Oftálmicas , Distribuição Aleatória , Timolol/farmacologiaRESUMO
A functional alteration of the retina is present in patients suffering from uveitis. Because of the relation between the pineal gland and the retina we documented possible modifications of melatonin secretion in patients with uveitis. Plasma melatonin was assayed in 19 patients and 16 age-matched controls. Blood samples were drawn at the known high and low points of the circadian rhythm of the hormone, i.e. 02.00 and 11.00 h, respectively. We found that the nocturnal peak of plasma melatonin was greatly decreased (45%) in patients with uveitis. These data cannot be related to the impairment of retinal melatonin synthesis alone. The possibility exists that the decline of the nocturnal peak of melatonin we have reported is due to a pineal inflammation in patients with uveitis, as observed in the experimental autoimmune uveitis induced in rats by retinal S-antigen.
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Melatonina/sangue , Retina/fisiopatologia , Uveíte/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Pineal/fisiopatologia , Radioimunoensaio , Uveíte/sangue , Uveíte/etiologiaRESUMO
A familial association between juvenile macular dystrophy and congenital hypotrichosis is described in two siblings aged 25 and 23 years. We put forward arguments for locating the retinal alteration at the level of the retinal pigment epithelium and suggest that the hair disorder could be a Marie-Unna type hypotrichosis. This association is transmitted as an autosomal recessive condition.
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Cabelo/anormalidades , Hipotricose/congênito , Hipotricose/genética , Degeneração Macular/genética , Adulto , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Linhagem , Retina/patologiaRESUMO
OBJECTIVE: To study the long term effects of monthly intravenous cyclophosphamide therapy in Wegener's granulomatosis. METHODS: Fourteen consecutive patients with active Wegener's granulomatos treated with a first-line combination of high-dose prednisone and monthly intravenous pulse cyclophosphamide were retrospectively studied. RESULTS: One patient died from septicemia complicating severe leukopenia after the first pulse. At 8 months after instituting intravenous pulse cyclophosphamide therapy, failure was observed in 6 other patients. Between month 16 and 18, 2 other patients relapsed when the time between 2 pulses was lengthened. Five patients developed cyclophosphamide-related side-effects: infection (n = 2), amenorrhea (n = 1), alopecia (n = 2) and vomiting (n = 2). Except for one fatal infection, no major side-effect of intravenous cyclophosphamide therapy was observed. At the end of the study, all patients were off intravenous cyclophosphamide therapy with more than 6 months of followup. The 6 responders were in remission on low-dose prednisone or without treatment. CONCLUSION: A combination of high-dose prednisone and intravenous cyclophosphamide may achieve long-term remission in 42% of patients with Wegener's granulomatosis. Responders to intravenous cyclophosphamide therapy had less extensive disease than non-responders.
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Ciclofosfamida/administração & dosagem , Glucocorticoides/administração & dosagem , Granulomatose com Poliangiite/tratamento farmacológico , Imunossupressores/administração & dosagem , Prednisona/administração & dosagem , Adolescente , Adulto , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos RetrospectivosRESUMO
Foscarnet (FC) is a new antiviral agent which has been recently proposed for the treatment of severe cytomegalovirus (CMV) infections in immunocompromised patients. When used intravenously (i.v.), main adverse effects of FC are a fall in hemoglobin, and an increase in liver enzymes and serum calcium. Although increased serum creatinine have been noted in several patients, deterioration of renal function is often accounted for by the concomitant use of other nephrotoxic drugs, the severity of underlying disease or the presence of graft rejection. Consequently FC is often considered as a non or poorly nephrotoxic drug. We report 4 cases of acute renal failure (ARF) which can be exclusively attributed to FC. FC was used for CMV chorioretinitis in 3 AIDS patients and in one non-immunocompromised patient. ARF was diagnosed between the 6th and 15th day of treatment, with oligoanuria in two patients (one of whom required two hemodialysis periods). ARF was most likely secondary to acute toxic tubulopathy. Three patients did not receive any other nephrotoxic drug. The fourth patient received concomitantly sulfadiazine but renal function returned to baseline value after FC completion although sulfadiazine was continued. In conclusion, our 4 observations suggest that FC may be responsible for acute tubulopathy. We suggest that in these patients renal function should be carefully monitored and dehydration promptly corrected to limit the risk of nephrotoxicity.
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Síndrome da Imunodeficiência Adquirida/complicações , Injúria Renal Aguda/induzido quimicamente , Antivirais/efeitos adversos , Compostos Organofosforados/efeitos adversos , Ácido Fosfonoacéticos/efeitos adversos , Adulto , Antivirais/uso terapêutico , Coriorretinite/tratamento farmacológico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Feminino , Foscarnet , Humanos , Tolerância Imunológica , Masculino , Pessoa de Meia-Idade , Ácido Fosfonoacéticos/análogos & derivados , Ácido Fosfonoacéticos/uso terapêuticoRESUMO
Hemolytic uremic syndrome (HUS) has been reported in patients treated with cyclosporin A (CsA) following bone, hepatic and kidney transplantation. We report two patients with Behçet's disease (BD) under CsA treatment because of severe uveitis, who developed HUS several months after the initiation of treatment. Renal biopsies showed lesions consistent with the diagnosis of the arterial form of thrombotic microangiopathy: vascular thrombosis with extensive glomerular ischemia. Renal failure persisted after withdrawal of CsA: one patient is in chronic renal failure (CRF) with a 4-year follow-up; the other died after refusal of chronic hemodialysis. In our two patients, excessive doses of CsA with high trough levels are likely to have contributed to the development of HUS. A rapid adjustment of CsA doses and an early detection of signs of the microangiopathic process might have prevented this severe complication of CsA treatment.
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Síndrome de Behçet/tratamento farmacológico , Ciclosporinas/efeitos adversos , Síndrome Hemolítico-Urêmica/induzido quimicamente , Adulto , Membrana Basal/ultraestrutura , Síndrome Hemolítico-Urêmica/patologia , Humanos , Rim/irrigação sanguínea , Rim/patologia , Glomérulos Renais/ultraestrutura , Masculino , Organelas/ultraestrutura , Artéria Renal/ultraestruturaRESUMO
Concomitant renal and ocular lesions have been described in a few systemic diseases. The association of acute interstitial nephritis (AIN) and anterior uveitis without determined cause was first described in children. Recently, the same clinical association has been reported in adults. We report 3 cases of this association and present a review of the literature. Including our 3 patients, 7 cases of this association have been reported in adults. All patients were females aged 27-74 years. Initial symptoms were either ocular, or pseudoviral (fever, myalgia and fatigue). Histological renal studies revealed acute interstitial nephritis with tubular lesions. Immunofluorescence and electron microscopy were not contributive. Ocular prognosis was always good. In 5 patients, the evolution of renal function was excellent with complete resolution of acute renal failure within a few weeks. Chronic renal failure developed in two of the four patients who did not receive systemic steroid therapy (with evolution towards terminal renal failure in one patient). Three of the patients received 60 mg per day of prednisone and none of them developed chronic renal failure. Despite the small number of patients reported and the possibility of spontaneous regression, these data suggest a beneficial effect of systemic steroid therapy to prevent or reduce interstitial inflammation and subsequent fibrosis.
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Nefrite Intersticial/complicações , Uveíte Anterior/complicações , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Microscopia Eletrônica , Pessoa de Meia-Idade , Nefrite Intersticial/patologiaRESUMO
Ten patients with birdshot retinochoroidopathy, six with isolated retinal vasculitis and eight with Behçet's disease were treated with cyclosporine for one to three years. Autoantibodies to several retinal proteins, circulating lymphocyte subsets and cellular reactivity to S-antigen were evaluated repeatedly during this period. Autoantibody titers were similar in patients and in controls. However the serum content of antibodies to IRBP or S-antigen was lessened during inflammatory periods in some patients. In some sera, antibodies reacted with enzyme digested S-antigen preparations by immunoblot, whereas the same sera were negative for the native protein. A decrease of the CD4+ subpopulation of peripheral blood lymphocytes was associated with relapses of ocular inflammation in birdshot retinochoroidopathy. In this disease and in idiopathic retinal vasculitis, the positive lymphocyte stimulation test and basophil degranulation test with S-antigen were significantly most frequent in the period preceding a relapse of ocular inflammation. These tests could therefore be of predictive value for relapses occurring within the next few months.
Assuntos
Formação de Anticorpos/imunologia , Antígenos/imunologia , Doenças da Coroide/imunologia , Proteínas do Olho/imunologia , Imunidade Celular/imunologia , Doenças Retinianas/imunologia , Adulto , Complexo Antígeno-Anticorpo/sangue , Arrestina , Autoanticorpos/imunologia , Basófilos/imunologia , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/imunologia , Doenças da Coroide/tratamento farmacológico , Ciclosporinas/uso terapêutico , Feminino , Humanos , Testes Imunológicos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recidiva , Doenças Retinianas/tratamento farmacológico , Proteínas de Ligação ao Retinol/imunologia , Linfócitos T/imunologia , Vasculite/tratamento farmacológico , Vasculite/imunologiaRESUMO
The purpose of this study was to confirm that ophthalmological features seen in patients in Martinique, French West Indies, could be linked to infection by HTLV-I. The authors studied 93 HTLV-I infected patients divided into 70 patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 23 asymptomatic HTLV-I carriers. They did a complete ophthalmological examination with an assessment of lacrymal secretion by means of three tests: Shirmer 1, break-up time and rose Bengal. Some patients had a biopsy of secondary salivary glands. When possible, detection of HTLV-I antibodies was carried out in the aqueous humor. In 45 of the 93 patients (48.4%) the presence of dry keratoconjunctivitis was recorded. In 22 of these 45 cases, a biopsy of the secondary salivary glands showed the presence of lymphoplasmocytoid infiltrations comparable to the glandular changes that occur with Gougerot-Sjögren syndrome. Among the 93 patients, 15 cases of uveitis were noted (16.1%) with 13 cases of anterior uveitis and 11 cases of vitritis. The inflammation was bilateral in 9 cases (9/15 = 60%). Two cases of cotton wool spots, 3 cases of abnormalities in the distribution of the retinal pigment and 7 cases of corneal lesions were also noted. Higher levels of anti-HTLV-I antibodies were detected in the aqueous humor of 3 patients with uveitis. The coexistence of dry eye (keratoconjunctivitis), uveitis and retinal microangiopathy in patients who are suffering from HAM/TSP could suggest the involvement of an autoimmune or immunological mechanism in the physiopathology of the illness.