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1.
Adv Clin Exp Med ; 28(10): 1393-1401, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31518496

RESUMO

BACKGROUND: Cyclosporine-A (CsA) is widely used for immunosuppressive therapy in renal transplantation. Nephrotoxicity is the main dose-limiting undesirable consequence of CsA. Urotensin II (U-II), a novel peptide with a powerful influence on vascular biology, has been added to the list of potential renal vascular regulators. Upregulation of the urotensin receptors and elevation of plasma U-II levels are thought to possibly play a role in the etiology of renal failure. OBJECTIVES: The present study examines this hypothesis by evaluating renal function and histology with regard to the potential role of U-II and its antagonist, palosuran, in the pathogenesis of CsA-induced nephrotoxicity in rats. MATERIAL AND METHODS: Male Sprague-Dawley rats were treated with CsA (15 mg/kg, for 21 days, intraperitoneally) or CsA + palosuran (300 mg/kg, for 21 days). Renal function was measured and histopathology, U-II immunostaining and protein detection with western blotting of the kidneys were performed. RESULTS: Cyclosporine-A administration caused a marked decline in creatinine clearance (Ccr). Fractional sodium excretion (FENa) tended to increase in the CsA-treated rats. Plasma U-II levels decreased in the CsA-treated rats. Cyclosporine-A treatment resulted in a marked deterioration in renal histology and an increase in the expression of U-II protein in the kidneys. Palosuran's improvement of renal function manifested as a significant decrease in serum creatinine levels and a significant increase in urine creatinine levels, resulting in a marked increase in Ccr. Palosuran produced a significant normalization of kidney histology and prevented an increase in U-II expression. CONCLUSIONS: Cyclosporine-A-induced renal impairment was accompanied by an increase in U-II expression in kidneys and a contrary decrease in systemic U-II levels. Palosuran improved the condition of rats suffering from renal dysfunction by preventing the decrease in renal U-II expression without affecting the systemic levels of U-II. The protective effect of palosuran in CsA nephrotoxicity is possibly independent of its U-II receptor antagonism.


Assuntos
Ciclosporina/toxicidade , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Urotensinas/antagonistas & inibidores , Animais , Creatinina/sangue , Creatinina/urina , Ciclosporina/efeitos adversos , Imunossupressores , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Masculino , Modelos Animais , Quinolinas , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Ureia/análogos & derivados
2.
J Vet Intern Med ; 33(5): 2046-2056, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31393054

RESUMO

BACKGROUND: The etiology of idiopathic chronic hepatitis (ICH) in dogs is poorly understood, but evidence supports an immune-mediated pathogenesis in some dogs. OBJECTIVES: To describe a case series of dogs with presumed ICH treated with cyclosporine (CsA) with or without concurrent medications and to document the incidence of biochemical remission and factors associated with failure to attain remission. ANIMALS: Forty-eight client-owned dogs diagnosed with presumed ICH, treatment of which included CsA. METHODS: Two-institution, retrospective case series of dogs between 2010 and 2017. All dogs were treated with CsA with or without concurrent medications for ≥2 weeks. Data were collected from medical records. RESULTS: Biochemical remission (<1.1 times the upper limit of normal for alanine aminotransferase activity) was attained in 79% of dogs (38/48). Median dose of CsA at remission was 7.9 mg/kg/d (range, 2.5-12.7 mg/kg/d) and median time to remission was 2.5 months (range, 0.75-18 months). Concurrent hepatoprotectant treatment was not associated with likelihood of remission. Clinical score, ascites, hypoalbuminemia, hyperbilirubinemia, prolonged coagulation times, dose, and duration of treatment were not associated with the probability of remission or time to remission. Common adverse effects of CsA were gastrointestinal signs in 38% (18/48) and gingival hyperplasia in 25% (12/48) of treated dogs. CONCLUSION AND CLINICAL IMPORTANCE: A treatment regimen including CsA and frequent hepatoprotectant use resulted in biochemical remission of ICH in most dogs. None of the evaluated factors, including hepatoprotectant use, were significantly associated with likelihood of remission. Future prospective studies are indicated to evaluate CsA monotherapy in ICH dogs.


Assuntos
Ciclosporina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Hepatite Crônica/veterinária , Imunossupressores/uso terapêutico , Alanina Transaminase/sangue , Animais , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Doenças do Cão/patologia , Cães , Feminino , Hepatite Crônica/tratamento farmacológico , Hepatite Crônica/patologia , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/efeitos adversos , Substâncias Protetoras/uso terapêutico , Indução de Remissão , Estudos Retrospectivos
3.
Drug Des Devel Ther ; 13: 2305-2330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371924

RESUMO

Introduction: The efficacy of cyclosporine A (CsA) in the treatment of idiopathic membranous nephropathy (IMN) is unclear. This meta-analysis was conducted to assess the efficacy and the safety of CsA in the treatment of IMN in Asians. Methods: We searched the Pubmed, China Biomedical Database, CNKI, Wanfang Data, VIP, and EMBASE (November 30, 2018) systematically to identify the appropriate randomized controlled trials (RCTs) reporting the efficacy and the safety of CsA and glucocorticoid (GC) treatment vs other immunosuppressants and GC on patients with IMN in Asian populations. Results: The CsA treated group entered complete remission (CR) faster (3 months) than a cyclophosphamide (CTX) group. While the CsA group lower inefficacy rates and higher total remission (TR, CR, or partial remission) than the CTX group in the total treatment (3 months, 6 months, and 12 months), it had a higher relapse rate. As for the CsA group vs the tacrolimus (TAC) group, the TAC had a significant effect in increasing the CR and the TR, with decreased no remission. With the therapeutic regimens of CsA+GC vs CTX+GC, the CsA exhibited better efficacy in lowering the proteinuria levels only at 12 months, not at 3 months or 6 months. Severe events like leucopenia, hemorrhagic cystitis, and alopecia were observed in the CTX group. Gingival hyperplasia, hirsutism, and elevated blood pressure were reported only in the CsA group. Gastrointestinal syndrome, liver function lesion, happened more frequently in the CTX group, and elevated uric acid was more common in the CsA group. Conclusions: In brief, the CsA has better efficacy than the CTX group in the Asian population, with mild adverse effects but higher relapse rates in short-term treatment.


Assuntos
Grupo com Ancestrais do Continente Asiático , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Feminino , Humanos , Masculino
4.
Eur J Haematol ; 103(4): 433-441, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31381187

RESUMO

OBJECTIVES: This study aimed to identify the natural course of cytomegalovirus (CMV)/Epstein-Barr virus (EBV) after rabbit antithymocyte globulin and cyclosporine (rATG-CsA) for aplastic anemia (AA). METHODS: In 113 prospectively observed AA patients treated with rATG-CsA, the CMV/EBV cohort was classified into two groups by baseline viremic status: no viremia (CMV-G1, n = 112; EBV-G1, n = 98) and the presence of viremia (CMV-G2, n = 1; EBV-G2, n = 13). RESULTS: In CMV-G1, the mean CMV load increased up to 3 months but was completely resolved from 6 months. The mean EBV load of EBV-G1 showed a peak at 1 month and then gradually decreased over time but remained detectable throughout the observation period. EBV-G2 showed fluctuating EBV dynamics. With reactivation rates of 38.4% in CMV-G1 and 62.2% in EBV-G1, a longer time to rATG-CsA from diagnosis and a lower absolute lymphocyte count at 1 month from rATG-CsA were significantly associated with CMV and EBV reactivation, respectively. The mean peak CMV and EBV loads of patients with CMV-related (3.5%) and EBV-related (0.9%) diseases were evidently higher than those of the remaining patients without CMV and EBV diseases in the respective cohort. CONCLUSION: Considering frequent reactivation and distinct courses of CMV/EBV, virologic surveillance is recommended after rATG-CsA for AA.


Assuntos
Anemia Aplástica/complicações , Soro Antilinfocitário/efeitos adversos , Ciclosporina/efeitos adversos , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/virologia , Citomegalovirus , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4 , Ativação Viral , Adolescente , Adulto , Idoso , Anemia Aplástica/tratamento farmacológico , Soro Antilinfocitário/uso terapêutico , Ciclosporina/uso terapêutico , Infecções por Citomegalovirus/diagnóstico , Infecções por Vírus Epstein-Barr/diagnóstico , Feminino , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Carga Viral , Adulto Jovem
6.
Transplant Proc ; 51(7): 2339-2342, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31402251

RESUMO

PURPOSE: In comparison to cyclosporine (CsA), tacrolimus (Tac) seems to be more diabetogenic in renal transplant recipients, and post-transplant diabetes mellitus is more common in patients using Tac, especially during the first year after transplantation. However, at maintenance doses, there are no comparative data of insulin resistance (IR) in patients using Tac or CsA. The purpose of this study was to investigate the IR indexes in patients on maintenance doses of CsA or Tac. METHODS: Forty-five nondiabetic and nonobese renal transplant recipients participated in the study (M:F, 30:15; age, 36 ± 9 years); 27 patients were on CsA, and 18 were on Tac. All had stable graft function, were transplanted at least 6 months previously, and were receiving maintenance doses of steroids (5.0 mg/d), azathioprine or mycophenolate mofetil, and calcineurin inhibitors (CsA [2.14 ± 0.46 mg/kg/d] or Tac [0.06 ± 0.03 mg/kg/d]). IR was evaluated by the homeostasis model assessment (HOMA) index and composite body insulin sensitivity index. RESULTS: We did not determine any significant difference in the HOMA and composite body insulin sensitivity index levels among patients using CsA or Tac (1.5 ± 1.3 vs 1.5 ± 1.1, P > .05, and 9.9 ± 5.8 vs 14.6 ± 11.7, P > .05, respectively). There was a significant correlation between creatinine and HOMA values. CONCLUSION: There was no difference in IR indexes in renal transplant recipients receiving maintenance doses of either CsA or Tac.


Assuntos
Ciclosporina/efeitos adversos , Diabetes Mellitus/epidemiologia , Imunossupressores/efeitos adversos , Resistência à Insulina , Transplante de Rim , Tacrolimo/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplantados , Transplante Homólogo
7.
Transplant Proc ; 51(6): 1848-1852, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256869

RESUMO

The incidence rate of breast fibroadenomas is higher among female kidney transplant (KT) patients treated using cyclosporine (CsA) for immunosuppression than in the general population. As such, there is an effort to convert immunosuppression from CsA or tacrolimus to sirolimus. Our aim was to assess the reversibility of a breast fibroadenoma after conversion in a small cohort of female KT recipients. This was an open-label, single-arm study including 128 female KT recipients, with a positive finding of a breast fibroadenoma in 15. Lesions were classified according to the Breast Imaging Reporting and Data System (BIRADS). Among these 15, a total of 7 converted from tacrolimus to sirolimus and 8 converted from CsA. We measured the change in BIRADS category and hormone and cytokine levels from baseline to 12 months after conversion. The primary outcome was progression or reversal of existing fibroadenomas at 12 months after conversion. Secondary outcomes were differences in hormone and cytokine levels. Conversion from CsA or tacrolimus to sirolimus had no significant effect on the BIRADS classification. However, conversion to sirolimus did produce a significant decrease in the level of transforming growth factor ß cytokine, this level being closely associated with fibroadenomas. Conversion from a calcineurin inhibitor to sirolimus can block the progression of fibroadenomas. Further research is needed to confirm our results.


Assuntos
Neoplasias da Mama/induzido quimicamente , Inibidores de Calcineurina/efeitos adversos , Fibroadenoma/induzido quimicamente , Imunossupressores/administração & dosagem , Complicações Pós-Operatórias/induzido quimicamente , Sirolimo/administração & dosagem , Adulto , Neoplasias da Mama/epidemiologia , Ciclosporina/efeitos adversos , Substituição de Medicamentos/métodos , Feminino , Fibroadenoma/epidemiologia , Rejeição de Enxerto , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Imunossupressores/efeitos adversos , Incidência , Transplante de Rim/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Tacrolimo/efeitos adversos
9.
Curr Drug Metab ; 20(8): 656-664, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296157

RESUMO

BACKGROUND: Drug-induced Acute Kidney Injury (AKI) develops in 10-15% of patients who receive nephrotoxic medications. Urinary biomarkers of renal tubular dysfunction may detect nephrotoxicity early and predict AKI. METHODS: We prospectively studied patients who received aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors, and collected their serial urine while on therapy. Patients who developed drug-induced AKI (fulfilling KDIGO criteria) were matched with non-AKI controls in a 1:2 ratio. Their urine samples were batch-analyzed at time-intervals leading up to AKI onset; the latter benchmarked against the final day of nephrotoxic therapy in non- AKI controls. Biomarkers examined include clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor- 3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin; biomarkers were normalized with corresponding urine creatinine. RESULTS: Nine of 84 (11%) patients developed drug-induced AKI. Biomarkers from 7 AKI cases with pre-AKI samples were compared with those from 14 non-AKI controls. Corresponding mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2 (all p=NS). Most biomarker levels peaked before the onset of AKI. Median levels of 5 biomarkers were significantly higher in AKI cases than controls at 1-3 days before AKI onset (all µg/mmol): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)], all p<0.05; their AUROC for AKI prediction were >0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation. CONCLUSION: Serial surveillance of these biomarkers could improve the lead time for nephrotoxicity detection by days.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/urina , Adulto , Idoso , Aminoglicosídeos/efeitos adversos , Anfotericina B/efeitos adversos , Biomarcadores/urina , Inibidores de Calcineurina/efeitos adversos , Quimiocina CCL2/urina , Clusterina/urina , Ciclosporina/efeitos adversos , Cistatina C/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Masculino , Pessoa de Meia-Idade , Tacrolimo/efeitos adversos , Vancomicina/efeitos adversos , Microglobulina beta-2/urina
10.
N Engl J Med ; 381(1): 36-46, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31269364

RESUMO

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).


Assuntos
Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclosporina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Indução de Remissão , Rituximab/efeitos adversos , Falha de Tratamento , Adulto Jovem
11.
BMJ Case Rep ; 12(7)2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308187

RESUMO

Behçet's disease (BD) is a variable-vessel vasculitis which commonly presents with recurrent orogenital ulceration, skin lesions, visual disturbances and neurodeficits. Arterial involvement is seen variably in 8%-18% cases of BD, with common affliction of the carotid, pulmonary, aortic and iliofemoral arteries. Cardiac involvement in the form of myocarditis, myocardial infarction, pericarditis, cardiac dysrhythmias or valvular disease is also known in BD, although rarely. Sudden-onset chest pain in BD is a medical emergency, with acute coronary syndrome, pulmonary thromboembolism and rupture of aortic or pulmonary artery aneurysms being the commonly implicated causes. Here, we report a rare case of BD who presented with sudden-onset severe chest pain, the cause of which remained elusive despite extensive evaluation for the abovementioned causes. To the best of our knowledge, this is the first reported case of cyclosporine-induced pericarditis in BD in available literature and should be considered in patients on cyclosporine presenting with chest pain.


Assuntos
Síndrome de Behçet/tratamento farmacológico , Dor no Peito/induzido quimicamente , Ciclosporina/efeitos adversos , Imunossupressores/efeitos adversos , Pericardite/induzido quimicamente , Adolescente , Síndrome de Behçet/complicações , Diagnóstico Diferencial , Substituição de Medicamentos , Humanos , Masculino , Pericardite/diagnóstico
12.
Clin Nephrol ; 92(3): 131-140, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31232271

RESUMO

BACKGROUND: A few clinical trials in IgA nephropathy (IgAN) have shown that cyclosporine A (CyA) had therapeutic efficacy in reducing proteinuria. MATERIALS AND METHODS: This is a retrospective study, and all cases were selected based on kidney biopsy-proven IgAN. We reviewed the data of IgAN patients in the glomerulonephritis registry at Kyung Hee University Medical center and collected data on 86 patients with urinary protein/Cr ratio (PCR; g/g) > 0.5 and estimated GFR (eGFR) of > 50 mL/min/1.73m2 who were treated with combination therapy of low-dose CyA plus low-dose steroid (C+P; n = 37) and high-dose steroid single therapy (P; n = 49). RESULTS: In the C+P group, the mean duration of therapy was 14.5 ± 13.1 months, and the mean duration of follow-up 66.2 ± 36.3 months. In the C+P group, the urine PCR levels significantly declined after treatment (< 0.05). After 6 months of treatment, 12 (32%) patients were in complete remission and 7 (19%) in partial remission in the C+P group, compared with 21 (42%) and 11 (22%) in the P group, respectively. Urine PCR levels were also significantly reduced in 12 patients in the C+P group who had initial urine PCR between 0.5 and 1.0. The degree of hematuria was significantly reduced after treatment in the C+P group. These effects of C+P therapy on proteinuria and hematuria were very comparable to high-dose P therapy. After 2 years, a decline in renal function, > 25% decrease in eGFR from baseline levels, developed in 3 (8.1%) in the C+P group, compared with 4 (8.2%) in the P group. The rate of decline in renal function during follow-up was -0.14 ± 0.40 mL/min/1.73m2/month in the C+P group compared with -0.12 ± 0.22 mL/min/1.73m2/month in the P group. There were no changes of mean eGFR during the first 24 months, but the eGFR significantly decreased at last follow-up in both groups. When patients in the C+P group were divided into progressive (n = 9) and nonprogressive (n = 28) groups, a significant reduction in the amount of proteinuria after treatment was observed in the nonprogressive group, in contrast to the progressive group. In the C+P group, there were no severe adverse effects, especially no acute renal impairment, requiring discontinuation of CyA in this study. The incidence of infection was much lower in the C+P group than that in the P group. The limitation is that CyA acts to nonspecifically reduce proteinuria, so it requires long-term follow-up off CyA therapy for more than 2 years to determine. CONCLUSION: Our retrospective uncontrolled study provides only weak evidence that combination therapy of low-dose C+P could be an alternative to high-dose P therapy and be safe in adult IgAN patients with relatively normal renal function and proteinuria of > 0.5 g/g. Development of safe and effective therapy is still a major challenge requiring well-controlled prospective studies with this or other combination therapies.


Assuntos
Ciclosporina/administração & dosagem , Glomerulonefrite por IGA/tratamento farmacológico , Glucocorticoides/administração & dosagem , Imunossupressores/administração & dosagem , Adulto , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Glomerulonefrite por IGA/fisiopatologia , Glucocorticoides/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Proteinúria/prevenção & controle , Estudos Retrospectivos
13.
Artigo em Inglês | MEDLINE | ID: mdl-31152638

RESUMO

Posterior reversible encephalopathy syndrome (PRES) is one of the most serious complication after allogeneic stem cell transplantation in paediatric setting. It is most commonly reported as adverse event of immunosuppressive strategies during transplantation. We present a case of a 7 years old girl with myelodysplastic syndrome (MDS) treated with allogeneic stem cell transplantation (ASCT) at our department. Diagnosis of PRES was confirmed by imaging techniques during the first month after transplant and it was very likely connected with cyclosporine neurotoxicity. The aim of this article is to present our first experience in diagnosing and treating PRES in paediatric stem cell transplantation. Our experience showed that PRES is one of the reasons for higher transplant related mortality in children. Early prediction of factors contributing to PRES and closely monitoring of patient's vital signs, especially blood pressure, neurological status and vision are the main contributors for challenging the patient with another immunosuppressive agent that has less neurological toxicity. Still studies have to be initiated to confirm the influence of PRES on transplant outcome.


Assuntos
Ciclosporina/efeitos adversos , Imunossupressores/efeitos adversos , Síndromes Mielodisplásicas/terapia , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Criança , Ciclosporina/uso terapêutico , Evolução Fatal , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Síndromes Neurotóxicas/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/tratamento farmacológico , Transplante de Células-Tronco/métodos , Transplante Homólogo/métodos
14.
Artigo em Inglês | MEDLINE | ID: mdl-31152642

RESUMO

We describe the clinical course of a patient who developed high-grade lymphoma during immunosuppression treatment with cyclosporine A, following liver transplantation. After anti-neoplastic polychemotherapy treatment, the remission of lymphoma was confirmed and maintained for over four years. The patient, a 27 year old female had liver transplantation at the age of 17, due to acute liver failure, caused by non-diagnosed Wilson disease. Nearly seven years post-transplantation, the patient was diagnosed with non-Hodgkin B-cell lymphoma (NHBCL), potentially induced by Cephalosporin A therapy. After the treatment with rituximab and CHOP therapy (r-CHOP protocol), remission was determined using computer tomography. Remission is maintained to date. A review of reported cases of post-transplant lymphoproliferative disorders (PTLDs) in liver transplanted (LT) patients showed that the onset of PTLDs is the highest in the first year after transplantation. In addition, remission rates of NHBCL in LT patients are not much elaborated in the literature. It is our opinion that the presented case is rare, both from the aspect of timeline of occurrence of the PTLD and the achieved remission, using r-CHOP protocol.


Assuntos
Ciclosporina/efeitos adversos , Imunossupressores/efeitos adversos , Transplante de Fígado/efeitos adversos , Linfoma não Hodgkin/induzido quimicamente , Adulto , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Transtornos Linfoproliferativos/induzido quimicamente , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Indução de Remissão , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Vincristina/administração & dosagem , Vincristina/uso terapêutico
15.
Medicentro (Villa Clara) ; 23(2): 145-150, abr.-jun. 2019. graf
Artigo em Espanhol | LILACS | ID: biblio-1002576

RESUMO

Resumen El agrandamiento gingival medicamentoso se describe como un aumento de volumen anormal, exagerado y deformante de las encías, provocado por la ingesta de algunos medicamentos. Entre los más comunes se encuentran: fármacos anticonvulsivantes, antihipertensivos, particularmente los antagonistas del calcio e inmunosupresores. Se presentó el caso de un paciente del sexo masculino, de 44 años de edad, con antecedentes de hipertensión arterial e insuficiencia renal crónica, durante 10 y tres años respectivamente. Después de 22 meses de haber recibido un trasplante renal y tratamiento con ciclosporina, acude a consulta por aumento del volumen de las encías en ambos maxilares, clínicamente compatible con agrandamiento gingival medicamentoso generalizado y grave.


ABSTRACT Drug-induced gingival enlargement is described as an abnormal, exaggerated, and deforming growth of the gingiva caused by the ingestion of some medications. Anticonvulsants, antihypertensive calcium channel blockers and immunosuppressants are among the most common drugs. We present a 44-year-old male patient with a history of arterial hypertension and chronic renal failure, for 10 and three years, respectively. Twenty-two months after receiving a kidney transplant and treatment with cyclosporine, he visited the clinic due to an increase in the volume of the gums in both jaws, clinically compatible with a generalized and severe gingival enlargement.


Assuntos
Ciclosporina/efeitos adversos , Crescimento Excessivo da Gengiva/induzido quimicamente
16.
BMJ Case Rep ; 12(5)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31142490

RESUMO

Drug-induced gingival overgrowth is a condition caused by side effects of treatment with one of three types of drugs: phenytoin (used in epilepsy treatment), cyclosporine A (used in transplantology after allogenic organ transplants) and calcium channel blockers (used in the treatment of hypertension). Gingival overgrowth leads to inflammation within the gums and periodontium and can amplify the existing periodontal disease leading to tooth loss. Patients who have undergone kidney transplant are given immunosuppressants to prevent transplant rejection and mostly it is accompanied with calcium channel blockers to treat hypertension associated with kidney transplant. This article reports a case of recent gingival enlargement associated with cyclosporine A and amlodipine given to a kidney transplant patient from the past 11 years.


Assuntos
Anlodipino/efeitos adversos , Ciclosporina/efeitos adversos , Crescimento Excessivo da Gengiva/induzido quimicamente , Imunossupressores/efeitos adversos , Transplante de Rim , Adulto , Anlodipino/administração & dosagem , Quimioterapia Combinada , Humanos , Masculino , Ácido Micofenólico/efeitos adversos
17.
Acta Derm Venereol ; 99(10): 851-857, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31099402

RESUMO

Dupilumab is approved for uncontrolled moderate-to-severe atopic dermatitis (AD); cyclosporine is approved for severe AD for ≤ 1 year. The efficacy/effectiveness of these treat-ments was compared indirectly. Regression models used pooled patient-level data to estimate response (Eczema Area and Severity Index (EASI) EASI-50/EASI-75 at weeks 12-16 and 24-30) to dupilumab 300 mg every 2 weeks (CHRONOS [NCT02260986]) or cyclosporine (University Medical Center). Models were adjusted for sex, baseline EASI, and thymus and activation-regulated chemokine level. A total of 106 patients received dupilumab (+ topical cortico-steroids; + TCS), and 57 received cyclosporine (+ TCS). Among University Medical Center patients, estimated EASI-50 responders were, dupilumab vs. cyclosporine, 91% vs. 77% (p = 0.038; weeks 12-16), and 96% vs. 67% (p < 0.0001; weeks 24-30); EASI-75 responders were 78% vs. 56% (p = 0.016; weeks 12-16) and 80% vs. 47% (p <0.001; weeks 24-30). Among CHRONOS patients, estimated EASI-50 responders were 90% vs. 74% (p <0.038; weeks 12-16) and 92% vs. 53% (p < 0.0001; weeks 24-30); EASI-75 responders were 75% vs. 52% (p = 0.016; weeks 12-16) and 74% vs. 40% (p <0.001; weeks 24-30), respectively. These results suggest a higher relative efficacy of dupilumab vs. cyclosporine.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Ciclosporina/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Imunossupressores/uso terapêutico , Pele/efeitos dos fármacos , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Ensaios Clínicos como Assunto , Ciclosporina/efeitos adversos , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Fármacos Dermatológicos/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Pele/imunologia , Pele/patologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Rev Assoc Med Bras (1992) ; 65(4): 530-534, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31066805

RESUMO

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Imunossupressores/administração & dosagem , Psoríase/tratamento farmacológico , Acitretina/administração & dosagem , Acitretina/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Brasil , Tomada de Decisão Clínica , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Psoríase/patologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
19.
J Am Acad Dermatol ; 81(3): 694-701, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31048013

RESUMO

BACKGROUND: Despite widespread use of steroid-sparing agents, particularly cyclosporine, for treatment of alopecia areata (AA), there are no clinical trials investigating the efficacy of these agents. OBJECTIVE: To evaluate the efficacy of cyclosporine compared with placebo at 3 months in patients aged 18 to 65 years with moderate-to-severe AA. METHODS: A double-blind, randomized, placebo-controlled trial was conducted. Adults aged 18 to 65 years of age with moderate-to-severe AA were randomized in a 1:1 ratio to receive 3 months of cyclosporine (4 mg/kg/d) or matching placebo. Blinded assessments included physical examination, blood biochemistry, photography, quality of life measurements, and efficacy evaluation using Severity of Alopecia Tool score and eyelash and eyebrow assessment scales. RESULTS: The results obtained for 32 participants (16 who received cyclosporine and 16 who received placebo) were analyzed. Compared with the placebo group, the cyclosporine group had a greater proportion of participants achieving at least a 50% reduction in Severity of Alopecia Tool score (31.3% vs 6.3% [P = .07]) and greater proportion of participants achieving a 1-grade improvement in eyelash (18.8% vs 0% [P = .07]) and eyebrow (31.3% vs 0% [P = .02]) scale score. LIMITATIONS: Small sample size and single-institution trial may limit interpretation and generalizability of these results. CONCLUSION: Response approached but did not reach a statistically significant difference between cyclosporine and placebo.


Assuntos
Alopecia em Áreas/tratamento farmacológico , Ciclosporina/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Administração Tópica , Adolescente , Adulto , Idoso , Alopecia em Áreas/diagnóstico , Ciclosporina/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Placebos/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
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