931 resultados para DOSE IMMUNOSUPPRESSIVE THERAPY
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Objective. To assess the efficacy and safety of pandemic 2009 influenza A (H1N1) in SLE under different therapeutic regimens. Methods. A total of 555 SLE patients and 170 healthy controls were vaccinated with a single dose of a non-adjuvanted preparation. According to current therapy, patients were initially classified as SLE No Therapy (n = 75) and SLE with Therapy (n = 480). Subsequent evaluations included groups under monotherapy: chloroquine (CQ) (n = 105), prednisone (PRED) epsilon 20 mg (n = 76), immunosuppressor (IS) (n = 95) and those with a combination of these drugs. Anti-H1N1 titres and seroconversion (SC) rate were evaluated at entry and 21 days post-vaccination. Results. The SLE with Therapy group had lower SC compared with healthy controls (59.0 vs 80.0%; P < 0.0001), whereas the SLE No Therapy group had equivalent SC (72 vs 80.0%; P = 0.18) compared with healthy controls. Further comparison revealed that the SC of SLE No Therapy (72%) was similar to the CQ group (69.5%; P = 0.75), but it was significantly reduced in PRED epsilon 20 mg (53.9%; P = 0.028), IS (55.7%; P = 0.035) and PRED epsilon 20 mg + IS (45.4%; P = 0.038). The concomitant use of CQ in each of these later regimens was associated with SC responses comparable with SLE No Therapy group (72%): PRED epsilon 20 mg + CQ (71.4%; P = 1.00), IS + CQ (65.2%; P = 0.54) and PRED epsilon 20 mg + IS + CQ (57.4%; P = 0.09). Conclusion. Pandemic influenza A H1N1/2009 vaccine response is diminished in SLE under immunosuppressive therapy and antimalarials seems to restore this immunogenicity.
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Objectives The aim of the present paper is to assess the influence of demographic, muscle enzymes, JDM scores and treatment on non-adjuvanted influenza A H1N1/2009 vaccine immunogenicity in juvenile dermatomyositis (JDM) patients. Methods Thirty JDM patients and 81 healthy age-matched controls were vaccinated. All participants were evaluated pre- and 21 days post-vaccination and serology for anti-HI NI was performed by haemagglutination inhibition assay. Muscle enzymes, JDM scores and treatment were evaluated before and after vaccination. Adverse events were reported. Results After immunisation seroconversion rates were significantly lower in JDM patients compared to age-matched controls (86.7 vs. 97.5%, p=0.044), whereas seropmtection (p=0.121), geometric mean titres (GMT) (p=0.992) and factor increase (FI) in GMT (p=0.827) were similar in both groups. Clinical and labomtorial evaluations revealed that JDM scores and muscle enzymes remained stable throughout the study (p>0.05). A higher frequency of chronic course was observed in non-seroconverted compared to seroconverted (100% vs. 27%, p=0.012). Regarding treatment, a lower rate of seroconversion was observed in patients under prednisone>20mg/day (50% vs. 4%, p=0.039), and in those treated with a combination of prednisone, methotrexate and cyclosporine (50% vs. 4%, p=0.039). Local and systemic vaccine adverse events were mild and similar in patients and controls (p>0.05). Conclusion This study identified that chronic course and immunosuppressive therapy are the major factors hampering seroconversion was JDM, suggesting that a specific protocol may be required for this subgroup of patients. In spite of that, a single dose of non-adjuvanted influenza A/H1N1 2009 vaccine was generally seroprotective in this disease with no evident deleterious effect in disease itself (ClinicalTrials.gov, no. NCT01151644).
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BACKGROUNDS: Cyclophosphamide and high-dose steroids have been used as limited induction therapy in progressive IgA nephropathy (IgAN) to reduce the loss of renal function and proteinuria. We evaluated the effect of cyclophosphamide pulses (CyP) and mycophenolic acid (MPA) as sequential therapy on renal function in patients with progressive IgAN. METHODS: Twenty patients with progressive IgAN and advanced renal failure (median GFR 22 ml/min per 1.73 m2) and further disease activity (triangle downGFR -0.8 ml/min per month) after cyclophosphamide (CyP; n = 18) or steroid pulse therapy (n = 2) were treated with mycophenolate mofetil 1 g per day for a median of 27 months. RESULTS: The monthly loss of renal function was significantly reduced in linear regression analysis from -2.4 ml/min before CyP to -0.12 ml/min with CyP/MPA (p = 0.0009). Estimated renal survival time was significantly prolonged by a median of 65 months (p = 0.0014). Proteinuria decreased significantly from 1.7 to 0.4 g/l during MPA treatment (p = 0.015). In Cox regression analysis, only proteinuria >1.0 g/l was an independent risk factor for doubling of creatinine during CyP/MPA treatment (p = 0.03). CONCLUSION: A sequential therapy with CyP/MPA may arrest or slow down the loss of renal function and reduces proteinuria even in patients who passed the so called 'point of no return' with progressive IgAN.
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The toxicity of long-term immunosuppressive therapy has become a major concern in long-term follow-up of heart transplant recipients. In this respect the quality of renal function is undoubtedly linked to cyclosporin A (CsA) drug levels. In cardiac transplantation, specific CsA trough levels have historically been maintained between 250 and 350 micrograms/L in many centers without direct evidence for the necessity of such high levels while using triple-drug immunosuppression. This retrospective analysis compares the incidence of acute and chronic graft rejection as well as overall mortality between groups of patients with high (250 to 350 micrograms/L) and low (150 to 250 micrograms/L) specific CsA trough levels. A total of 332 patients who underwent heart transplantation between October 1985 and October 1992 with a minimum follow-up of 30 days were included in this study (46 women and 276 men; aged, 44 +/- 12 years; mean follow-up, 1,122 +/- 777 days). Standard triple-drug immunosuppression included first-year specific CsA target trough levels of 250 to 300 micrograms/L. Patients were grouped according to their average creatinine level in the first postoperative year (group I, < 130 mumol/L, n = 234; group II, > or = 130 mumol/L, n = 98). The overall 5-year survival excluding the early 30-day mortality was 92% (group I, 216/232) and 91% (group II, 89/98) with 75% of the mortality due to chronic rejection. The rate of rejection for the entire follow-up period was similar in both groups (first year: group I, 3.2 +/- 2.6 rejection/patient/year; group II, 3.6 +/- 2.7 rejection/patient/year; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)
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The possible carcinogenic risk of immunosuppressive therapies is an important issue in everyday clinical practise. Carcinogenesis is a slow multi step procedure, thus a long latency period is needed before cancer develops. PUVA therapy is used for many skin diseases including psoriasis, early stage cutaneous T cell lymphoma, atopic dermatitis, palmoplantar pustulosis and chronic eczema. There has been concern about the increased melanoma risk associated to PUVA therapy, which has previously been associated with an increased risk on non-melanoma skin cancer, especially squamous cell carcinoma. The increased risk of basal cell carcinoma (BCC) is also documented but it is modest compared to squamous cell carcinoma (SCC). This thesis evaluated melanoma and noncutaneous cancer risk associated to PUVA, and the persistence of nonmelanoma cancer risk after the cessation of PUVA treatment. Also, the influence of photochemotherapy to the development of secondary cancers in cutaneous T cell lymphoma and the role of short term cyclosporine in later cancer development in inflammatory skin diseases were evaluated. The first three studies were performed on psoriasis patients. The risk of melanoma started to increase 15 years after the first treatment with PUVA. The risk was highest among persons who had received over 250 treatments compared to those under 250 treatments. In noncutaneous cancer, the overall risk was not increased (RR=1.08,95% CI=0.93-1.24), but significant increases in risk were found in thyroid cancer, breast cancer and in central nervous system neoplasms. These cancers were not associated to PUVA. The increased risk of SCC was associated to high cumulative UVA exposure in the PUVA regimen. The patients with high risk had no substantial exposure to other carcinogens. In BCC there was a similar but more modest tendency. In the two other studies, the risk of all secondary cancers (SIR) in CTCL patients was 1.4 (95% CI=1.0-1.9). In separate sites, the risk of lung cancer, Hodgkin and non-Hodgkin lymphomas were increased. PUVA seemed not to contribute to any extent to the appearance of these cancers. The carcinogenity of short-term cyclosporine was evaluated in inflammatory skin diseases. No increased risk for any type of cancer including the skin cancers was detected. To conclude, our studies confirm the increased skin cancer risk related to PUVA treatment in psoriasis patients. In clinical practice, this has led to a close and permanent follow-up of patients treated with PUVA. In CTCL patients, PUVA treatment did not contribute to the development of secondary cancers. We could not detect any increase in the risk of cancer in patients treated with short term cyclosporine, unlike in organ transplant patients under such long-term therapy.
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Importance of the field: Type 2 diabetes is typically associated with insulin resistance and dysfunction of insulin-secreting pancreatic beta-cells. Addressing these defects often requires therapy with a combination of differently acting antidiabetic agents. A potential novel combination in development brings together the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin with the thiazolidinedione pioglitazone into a fixed-dose single-tablet combination. The former component acts mainly to increase prandial insulin secretion; the latter improves insulin sensitivity.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Malakoplakia is a rare chronic granulomatous disease of unknown cause. It is thought to be caused by an acquired bactericidal defect of macrophages. Malakoplakia is associated with chronic infections and immunosuppression. Although it occurs mainly in the urinary tract, it has already been reported in almost every organ system. The isolation of bacteria, especially Escherichia coli, is common in malakoplakia patients. Here, we present a case of primary cutaneous malakoplakia in a kidney transplant recipient who had been taking prednisone, tacrolimus, and mycophenolate. Culture of a lesion grew Burkholderia cepacia complex. Treatment with high doses of trimethoprim-sulfamethoxazole was successful. We also present a systematic review of the literature, identifying 4 previously reported cases of malakoplakia after renal transplantation under similar immunosuppressive therapy, most occurring in the urinary tract or perineum and following benign courses to cure. Data in the literature suggest that malakoplakia has become even rarer since changes were made in the immunosuppressive therapy employed after kidney transplantation.
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We describe a 61-year-old patient with clinical evidence of limbic encephalitis who improved with anticonvulsant treatment only, that is, without the use of immunosuppressive agents. Three years following occurrence of anosmia, increasing memory deficits, and emotional disturbances, he presented with new-onset temporal lobe epilepsy, with antibodies binding to neuronal voltage-gated potassium channels and bitemporal hypometabolism on FDG-PET scan; the MRI scan was normal. This is most likely a case of spontaneous remission, illustrating that immunosuppressive therapy might be suspended in milder courses of limbic encephalitis. It remains open whether treatment with anticonvulsant drugs played an additional beneficiary role through the direct suppression of seizures or, additionally, through indirect immunomodulatory side effects.