PubMed · 9217855
Rhinosinusitis, inflammation of the lining of the nose and paranasal sinuses, has a range of different causes. This article considers the classification, diagnosis and treatment of rhinosinusitis.
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V J Lund. Rhinosinusitis.. https://pubmed.ncbi.nlm.nih.gov/9217855/
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BACKGROUND: Exposure, safety, and efficacy data from the two everolimus randomized, double-blind phase 3 trials were evaluated to identify a therapeutic concentration range applicable in de novo kidney transplantation. METHODS: A total of 695 evaluable everolimus-treated patients received either 0.75 or 1.5 mg bid in addition to corticosteroids and cyclosporine (troughs 150-400 ng/ml in month 1 and 100-300 ng/ml thereafter). A total of 3355 everolimus trough levels (Cmin) were obtained in weeks 1 and 2 and months 1, 2, 3, and 6 after transplantation. Each patient's average Cmin was calculated and the values were divided into quintiles: 1.0-3.4, 3.5-4.5, 4.6-5.7, 5.8-7.7, 7.8-15.0 ng/ml (139 patients per quintile). Efficacy was freedom from biopsy-confirmed acute rejection. Safety measures were maximum total cholesterol and triglyceride levels and minimum leukocyte and platelet counts. A sigmoid exposure-response model was used to test the significance of these Cmin-efficacy and Cmin-safety relationships. RESULTS: Freedom from acute rejection was significantly related to Cmin with an incidence of 68% at 1.0-3.4 ng/ml, 81-86% at 3.5-7.7 ng/ml, and 91% at 7.8-15.0 ng/ml (P=0.03). The incidence of hypercholesterolemia, defined as >6.5 mmol/liter, ranged from 76 to 87% over the exposure range without a significant relation to Cmin (P=0.37). The incidence of hypertriglyceridemia, defined as >2.9 mmol/liter, rose from 59 to 77% across the exposure groups (P=0.02). Leukocytopenia, defined as <4x10(9)/liter, occurred in 11-19% of patients across the exposure quintiles showing no relationship to Cmin (P=0.76). The incidence of thrombocytopenia, defined as <100x10(9)/liter, occurred in </=10% of patients in the first 3 Cmin quintiles and was 14 and 17% in Cmin quintiles 4 and 5 (P=0.21). CONCLUSIONS: A significantly increased risk of acute rejection was observed at everolimus trough levels <3 ng/ml. This is a lower therapeutic concentration limit when everolimus is used with conventionally dosed cyclosporine. Because hyperlipidemias responded to counter-measure therapies and thrombocytopenia had an overall low incidence of 12%, everolimus-related adverse events were manageable up to the highest troughs observed in this population of 15 ng/ml. An upper therapeutic concentration limit is likely more than 15 ng/ml but a precise value could not be derived from these data.
BACKGROUND: Administration of corticosteroids to kidney recipients has hampered the complete clinical success of kidney transplantation. Because most organ transplantation in Japan is living-related, we had the experience of performing kidney transplantation (KT) after liver transplantation (LT) from the same donor in four patients and successfully withdrew corticosteroid administration. METHODS: Three pediatric and one adult patient received kidney allografts from 3 to 10 months after LT from the same donor. The immunosuppressive regimen consisted of a corticosteroid and tacrolimus. The steroid was withdrawn after KT in all four patients. After complete withdrawal of the steroid, DNA was extracted from two recipients and examined by polymerase chain reaction to detect microchimerism. A mixed lymphocyte reaction (MLR) and cell-mediated lymphocytotoxicity assay (CML) were performed to test for donor-specific hyporesponsiveness. RESULTS: Steroid withdrawal was successfully accomplished after KT in every patient. No steroid-withdrawal-associated complications were observed. In the three pediatric patients, remarkable catch-up growth was observed after steroid withdrawal. In the two patients tested, donor DNA was not detected by polymerase chain reaction, suggesting the absence of microchimerism. MLR and CML showed that recipient lymphocytes reacted against donor lymphocytes at the same level as against the third-party lymphocytes. CONCLUSION: Steroid withdrawal was successfully achieved in four kidney recipients who had received a liver allograft from the same donor. The MLR and CML findings indicated the absence of donor-specific hyporesponsiveness in vitro. Although the precise mechanism is not yet clear, KT after LT from the same donor should be considered as a method that allows steroids to be withdrawn from the immunosuppressive regimen of KT.
BACKGROUND: Outbreaks of eosinophilic meningitis caused by the roundworm Angiostrongylus cantonensis are rarely reported, even in regions of endemic infection such as Southeast Asia and the Pacific Basin. We report an outbreak of A. cantonensis meningitis among travelers returning from the Caribbean. METHODS: We conducted a retrospective cohort study among 23 young adults who had traveled to Jamaica. We used a clinical definition of eosinophilic meningitis that included headache that began within 35 days after the trip plus at least one of the following: neck pain, nuchal rigidity, altered cutaneous sensations, photophobia, or visual disturbances. RESULTS: Twelve travelers met the case definition for eosinophilic meningitis. The symptoms began a median of 11 days (range, 6 to 31) after their return to the United States. Eosinophilia was eventually documented in all nine patients who were hospitalized, although on initial evaluation, it was present in the peripheral blood of only four of the nine (44 percent) and in the cerebrospinal fluid of five (56 percent). Repeated lumbar punctures and corticosteroid therapy led to improvement in symptoms in two of three patients with severe headache, and intracranial pressure decreased during corticosteroid therapy in all three. Consumption of one meal (P=0.001) and of a Caesar salad at that meal (P=0.007) were strongly associated with eosinophilic meningitis. Antibodies against an A. cantonensis--specific 31-kD antigen were detected in convalescent-phase serum samples from 11 patients. CONCLUSIONS: Among travelers at risk, the presence of headache, elevated intracranial pressure, and pleocytosis, with or without eosinophilia, particularly in association with paresthesias or hyperesthesias, should alert clinicians to the possibility of A. cantonensis infection.