A study of the pathogenesis and prevention of central pontine myelinolysis in a rat model.

The development of central pontine myelinolysis was studied in rats. Severe hyponatraemia was induced using vasopressin tannate and 2.5% dextrose in water and then rapidly corrected with hypertonic saline alone, hypertonic saline and dexamethasone simultaneously, or hypertonic saline plus dexamethasone 24 h later. The permeability of the blood-brain barrier was evaluated using the extravasation of Evans blue dye and the expression of inducible nitric oxide synthase (iNOS) in the brain was examined using Western blot analysis. Histological sections were examined for demyelinating lesions. In rats receiving hypertonic saline alone, Evans blue dye content and expression of iNOS began to increase 6 and 3 h, respectively, after rapid correction of hyponatraemia and demyelinating lesions were seen. When dexamethasone was given simultaneously with hypertonic saline, these increases were inhibited and demyelinating lesions were absent. These effects were lost if dexamethasone injection was delayed. Disruption of the blood-brain barrier and increased iNOS expression may be involved in the pathogenesis of central pontine myelinolysis, and early treatment with dexamethasone may help prevent the development of central pontine myelinolysis.

Concurrent IMRT and weekly cisplatin followed by GDP chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell lymphoma.

On the basis of the benefits of frontline radiation in early-stage, extranodal natural killer (NK)/T-cell lymphoma (ENKTL), we conducted the trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of gemcitabine, dexamethasone and cisplatin (GDP). Thirty-two patients with newly diagnosed, stage IE to IIE, nasal ENKTL received CCRT (that is, all patients received intensity-modulated radiotherapy 56 Gy and cisplatin 30 mg/m(2) weekly, 3-5 weeks). Three cycles of GDP (gemcitabine 1000 mg/m(2) intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1-4 and cisplatin 75 mg/m(2) i.v. on day 1 (GDP), every 21 days as an outpatient were scheduled after CCRT. All patients completed CCRT, which resulted in 100% response that included 24 complete responses (CRs) and eight partial responses. The CR rate after CCRT was 75.0% (that is, 24 of 32 responses). Twenty-eight of the 32 patients completed the planned three cycles of GDP, whereas four patients did not because they withdrew (n = 1) or because they had an infection (n = 3). The overall response rate and the CR rate were 90.6% (that is, 29 of 32 responses) and 84.4% (that is, 27 of 32 responses), respectively. Only two patient experienced grade 3 toxicity during CCRT (nausea), whereas 13 of the 30 patients experienced grade 4 neutropenia. The estimated 3-year overall survival and progression-free rates were 87.50% and 84.38%, respectively. In conclusion, CCRT followed by GDP chemotherapy can be a feasible and effective treatment strategy for stage IE to IIE nasal ENKTL.