Renal tubular acidosis associated with zonisamide therapy

PURPOSE: We sought to report a previously undescribed adverse effect, renal tubular acidosis associated with zonisamide (ZNS) therapy. METHODS: Ammonium chloride, bicarbonate, and furosemide loading tests were performed in an epileptic patient with metabolic acidosis and episodic hypokalemia who was treated with ZNS. RESULTS: Distal renal tubular acidosis was diagnosed. On reexamination 7 weeks after ZNS had been replaced with phenytoin, the renal tubular acidosis disappeared. CONCLUSIONS: This case indicates, for the first time, that ZNS might be a potential cause of renal tubular acidosis. Blood gases and serum electrolytes should be measured in patients undergoing ZNS therapy.     

Cytotoxic T cell activity against the peptide, AYRARALEL, from Yo protein of patients with the HLA A24 or B27 supertype and paraneoplastic cerebellar degeneration

OBJECTIVE: To determine a peptide that reacts with cytotoxic T cells (CTL) of patients with paraneoplastic cerebellar degeneration and anti-Yo antibodies with either HLA A24 or B27 supertype. METHOD: We studied CTL activity of four patients, three were HLA A24-positive and one did not have HLA A24 but had B27 supertype. After an incubation of mononuclear cells with or without peptide and IL-2, CD8-rich fraction was prepared by treatment with Magnetic Cell Sorting system (MACS) twice. CTL activity was calculated by 51Cr release from transfectant, C1RA*2402 as target cells. The peptide-binding assay was examined by flow cytometry. RESULTS: Two of three HLA A 24-positive patients demonstrated CTL activity against the Yo peptide, AYRARALEL. CTL activity was found to be 19.5% and 11.7% at the effector/target (E/T) ratio of 23:1 and 11:1, respectively. A patient who did not have HLA A24 but had A2 and B27 supertype possessed a CTL activity of 19.4% with 15:1 as E/T ratio. The peptide could bind to HLA A*2402 molecules but not to A*0201. CONCLUSIONS: We showed CTL activity in two of three Japanese patients with HLA A24 by using HLA A*2402 transfectant cells as the target. In addition, we identified the first Japanese patient who had B27 supertype, and suggested that the same peptide, AYRARALEL, could be recognized by CTL in this patient.     

Mapping therapeutic response in a patient with malignant glioma

Short-interval scanning of patients offers a detailed understanding of the natural progression of tumor tissue, as revealed through imaging markers such as contrast enhancement and edema, prior to therapy. Following treatment, short-interval scanning can also provide evidence of attenuation of growth rates. We present a longitudinal imaging study of a patient with glioblastoma multiforme (GBM) scanned 15 times in 104 days on a 3 T MR scanner. Images were analyzed independently by two automated algorithms capable of creating detailed maps of tumor changes as well as volumetric analysis. The algorithms, a nearest-neighbor-based tissue segmentation and a surface-modeling algorithm, tracked the patient's response to temozolomide, showing an attenuation of growth. The need for surrogate imaging end-points, of which growth rates are an example, is discussed. Further, the strengths of these algorithms, the insight gained by short-interval scanning, and the need for a better understanding of imaging markers are also described.     

Quantitative renography with the organ volume method and interporative background subtraction technique

When quantification of renal activity is performed by planar imaging, many correction factors must be considered. To obtain quantitative renal images and renogram, we have examined our proposed method by using the organ volume for scatter, attenuation, and background activity, and the interporative background subtraction (IBS) technique in phantom and clinical studies. A renal phantom study was performed by varying the renal depth from 3 to 11 cm and the kidney-to-background activity concentration ratio from 5 to 80. Planar images were properly corrected for scatter, attenuation and background activity by our method and the corrected images were compared with the images obtained by the conventional method for the estimation of true renal activity. Clinical Tc-99m DTPA dynamic data for both a good and a poor renal function were also corrected by our method and volume-corrected renograms were obtained. For the phantom study, depth-independent images were obtained and these images gave a good estimation of the true count rate. In the clinical study, the conventional renogram was especially modified to allow for oversubtraction of background counts in the early phase (0–4 min). In conclusion, our proposed correction method can assess renal function qualitatively and quantitatively in both static and dynamic planar renal imaging.     

Relationship between the HLA Associated Specificities 4a and 4b and the Lymphocyte C3 Receptor

Contrary to previous reports, we have obtained no evidence that 4a and 4b antisera specifically inhibit C3 rosette formation by human lymphocytes. Pretreatment of lymphocytes with various whole 4a and 4b antisera resulted in partial inhibition which was often nonsepcific. Ultracentrifugation of the sera to remove immune complexes removed C3 rosette inhibitory activity although specific cytotoxic activity remained. It is probable that immune complexes in antisera will have fixed C3 which will have been converted to C3d and so be able to block the C3d receptor. This is the receptor mainly measured in these and in the previous experiments.