A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome

BACKGROUND: The use of corticosteroids or cytotoxic/immunosuppressive agents such as cyclophosphamide, chlorambucil, and cyclosporine for the treatment of frequently relapsing nephrotic syndrome (FRNS) is limited because of their adverse effects. This study was conducted to evaluate the efficacy and safety of mizoribine, a relatively new immunosuppressive drug developed in Japan, in children with FRNS. METHODS: A double-blind, placebo-controlled, multicenter trial was carried out in children, from 2 to 19 years old, with FRNS. At relapse, patients were treated with prednisolone. According to a dynamic allocation, mizoribine or a placebo was concurrently administered to each patient. Prednisolone was gradually tapered and discontinued within 12 weeks. The test drug was maintained for 48 weeks. The primary end point was the relapse rate (the total number of relapses/the total treatment days for all patients). Analyses were performed according to the intention-to-treat principle. RESULTS: The primary analysis was conducted on 99 mizoribine- and 98 placebo-treated patients. The relapse rate was lower in the mizoribine group than in the placebo group (0.0055 vs. 0.0067; ratio 0.81, 95% CI, 0.61 to 1.05, P = 0.12). The hazard ratio of the cumulative remission rate between the two groups was 0.79 (95% CI, 0. 57 to 1.08). In the subgroups consisting of patients 10 years old or younger, the relapse rate ratio between the mizoribine subgroup (54 patients) and the placebo subgroup (57 patients) was 0.66 (95% CI, 0. 44 to 0.94, P = 0.017). The hazard ratio of the cumulative remission rate between the two subgroups was 0.56 (95% CI, 0.37 to 0.85, P = 0. 007). Hyperuricemia was the most common adverse event with mizoribine (16%), but was transient. CONCLUSIONS: Compared with the placebo, mizoribine significantly decreased the relapse rate and prolonged the remission period in the subgroup consisting of patients 10 years old or younger. This drug may be useful in young children with FRNS who generally relapse more frequently than older children.     

Diagnosis of chest wall invasion by lung cancer: useful criteria for exclusion of the possibility of chest wall invasion with MR imaging

PURPOSE: To compare the accuracy of thin-section CT, conventional static MR imaging (conventional MRI), and breathing dynamic echo planar magnetic resonance imaging (BDEPI) in evaluating lung cancer invasion to the chest wall. MATERIALS AND METHODS: Thin-section CT, conventional MRI, and BDEPI were performed preoperatively in 20 patients suspected of having primary lung cancers adjacent to the chest wall on conventional CT. The results of imaging findings were compared with those of surgical and histopathological findings. RESULTS: All patients were confirmed to have no chest wall invasion after surgery. By thin-section CT, 10 of 20 patients were correctly diagnosed as having no chest wall invasion (50% specificity). Two of the 20 patients were incorrectly diagnosed as having chest wall invasion by conventional MRI and BDEPI (90% specificity). CONCLUSION: When chest wall invasion is suspected on CT scans, static and breathing dynamic MRI are recommended to avoid false positive interpretations.     

Male mice lacking the gastrin-releasing peptide receptor (GRP-R) display elevated preference for conspecific odors and increased social investigatory behaviors

Previously, we generated gastrin-releasing peptide receptor null mutant mice (GRP-R-deficient mice), and found that these animals displayed increased non-aggressive social responses in an ordinary social interaction test using a resident-intruder method. In the present study, we examined in more detail the social behaviors of GRP-R-deficient male mice. In social interaction tests, GRP-R-deficient mice showed more social responses, such as sniffing and nosing, relative to wild-type mice, and similar results were obtained whether GRP-R-deficient mice served as intruders or residents. In the same way, they showed more contact behaviors toward an anesthetized conspecific, and less locomotor activity than wild-type mice in a social investigation test toward an anesthetized male mouse. Since olfactory systems play important roles in the social behavior of rodents, olfactory preference tests were conducted in order to evaluate the olfactory properties of GRP-R-deficient mice. The results suggest that no differences exist between wild-type mice and GRP-R-deficient mice in the preference between a novel sawdust odor and their own odor, or that of other male mice. However, GRP-R-deficient mice preferred the odor of other male mice to their own, in contrast to wild-type mice. Furthermore, the preferences of GRP-R-deficient and wild-type mice were not disrupted by intraperitoneal infusion of diazepam (1.5 mg/kg). These results indicate that neither the motion, nor the behavior of conspecifics, nor reduced anxiety lead to the increased non-aggressive social responses and/or social investigatory behaviors in GRP-R-deficient mice. Rather, these latter behaviors may be a consequence of altered cognition of conspecific odors in the mutant mice.     

A Case of Subcortical Meningioma

Subcortical meningioma, which has been reported as meningioma without dural attachment, a cerebral subcortical lesion, is extremely rare. Very few findings of radiological examination of subcortical meningioma have been described. Pre-operative differentiation of this lesion is generally difficult. We characterize the peritum oural oedema adjacent to the meningioma in this region, and we suggest that radiological findings of peritum oural oedema contribute to differential diagnosis of subcortical meningiomas.     

The effect of propofol anesthesia on striatal dopamine of awake freely moving and anesthetized rats examined by in vivo microdialysis study

We investigated the effect of propofol anesthesia on the level of interstitial dopamine in vivo awake free moving and anesthetized rats brain striatum using microdialysis techniques. Rats were implanted a microdialysis probe to right striatum of the brain and administered intravenously 20 mg.kg-1 of propofol for induction and followed by continuous infusion at 12.5, 25 and 50 mg.kg-1.hr-1 up to 1 hour. The microdialysis probe was perfused with artificial cerebrospinal fluid and dialysates from the probe were determined every 20 minutes by high performance liquid chromatography and electrochemical detection. Propofol anesthesia reduced the amount of dopamine derived from dialysate, but no prolonged increases of dopamine metabolites were observed, as we demonstrated in previous investigation for halothane, isoflurane or sevoflurane anesthesia. We hypothesize that the characteristics of propofol anesthesia for dopamine and its metabolites might contribute to low incidence of postoperative nausea and vomiting in its clinical use.     

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score–matched analysis

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score–matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.