High-dose intravenous immunoglobulin in the treatment of sensory ataxic neuropathy with Sj?gren's syndrome: a case report]

We report herein a case of sensory ataxic neuropathy with Sj?gren's syndrome (SS-SAN) who became dramatically improved in response to high-dose intravenous immunoglobulin treatment (IVIg). An 81-year-old man began to feel numbness in his hands and feet in August 2002. Because he became unsteady and could not do skillfull movement, he was admitted to our hospital in May 2003. On neurological examination, all tendon reflexes were absent. His vibratory and position senses were severely impaired to knees and elbows. Touch, temperature, and pinprick sensations were mildly disturbed in a glove-stocking distribution. Coordination was clumsy in all limbs because of sensory loss. He had gait ataxia with Romberg sign. Nerve conduction study revealed that sensory nerve action potentials were absent. He was diagnosed as having SS-SAN because Schirmer test, Saxon test and both SS-A and SS-B antibodies were positive. Thereafter, Mg, 400 mg/kg daily for 5 days, was administered. His sensory impairment began to improve 2 days after Mg. Subsequently, he could walk steadily without ataxia. It is considered that IVIg may be an effective treatment for SS-SAN.     

Prediction of ftorafur disposition in rats and man by a physiologically based pharmacokinetic model

A physiologically based pharmacokinetic model including fourteen compartments (artery, vein, and twelve tissues) was used to predict plasma and tissue ftorafur concentrations in rats after a 100 $\text{mg}\text{kg}$ i.v. dose. Fairly good agreement was obtained between the predicted and observed time courses of ftorafur concentrations in plasma and tissues. This model was also used to predict plasma ftorafur concentrations for man. Fairly good agreement was again obtained between the predicted and observed plasma ftorafur concentrations. Additionally, it was ascertained that the ratio of body weight (kg) to distribution volume (liter) of ftorafur was approximately 1:1 in man, rat, monkey, dog and rabbit, and the ratio of body weight (kg) to total body clearance ($\text{ml}\text{min}$) was the same in all cases except rabbit.     

One stage repair for an oesophageal fistula after pneumonectomy using an omental pedicle flap.

A 67 year old man developed an oesophageal fistula after a pneumonectomy that was complicated by an empyema. An omental pedicle flap was brought through the diaphragm to repair the fistula and to fill the empyema space. The outcome was successful.     

Use of Rokitamycin dry syrup in cases of upper deep cervical lymphadenitis and otitis media with exudatives

Dry syrup of Rokitamycin (RKM.DS), a new macrolide antibiotic with 16-membered ring developed by Toyo Jozo Co., Ltd., was used on cases of upper deep cervical lymphadenitis (UDCL) and of otitis media with exudatives (OME) likely caused by chlamydia infections, and its clinical effects were investigated. 1) In four cases of UDCL (C. psittaci infections), daily doses of 20.0-28.6 mg/kg were administered for 10-42 consecutive days and good efficacies were observed with two cases of excellent results and two cases of good results. 2) In one case of OME (C. trachomatis infection) a daily dose of 30.0 mg/kg was administered for 15 consecutive days and good effectiveness was observed. 3) No side effect was observed in any of the cases. From the above results, it became clear that RKM.DS could effectively used as a therapeutic agent for UDCL and OME in children.     

A case of tracheoesophageal fistula in Beh?et's disease repaired with pericardial patch and gastric roll

A 23-year-old man suffering from Beh?et's disease developed a tracheoesophageal fistula. Subtotal esophagus was stripped and replaced with a gastric tube along greater curvature. The defect of membranous portion of the trachea (2 X 1 cm) was closed with a pedicled pericardial patch and covered with omentum. Transient postoperative recurrent nerve palsy was recovered in about 2 months. He is going well without any significant complaints. He received steroid hormone administration and platelets transfusion because of complicated ITP (Idiopathic Thrombocytopenic Purpura).     

TRAIL-induced cell death cooperates with IFN-gamma activation in the graft-versus-tumor effect against colon tumors

The graft-versus-tumor (GVT) effect that occurs following allogeneic bone marrow transplantation (BMT) and donor lymphocyte infusion (DLI) is currently being subjected to intensive investigation because of clinical evidence for GVT efficacy against leukemia. In this report, we investigate the efficacy and molecular mechanisms of GVT against solid tumors, using a modification of the mouse parent-to-F1 BMT model. Mouse Colon26 cells in which tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptor expression was stably knocked down were transplanted to investigate the role of the TRAIL-TRAIL receptor system in the GVT effect. In addition, Fas ligand-(FasL) deficient mice on a C57BL6 (B6) background were used as donors, to determine the significance of the Fas-FasL system for the antitumor effect. The group that received B6 DLI followed by preconditioning with 950 rad irradiation underwent tumor reduction associated with the induction of IFN-gamma, TRAIL and tumor-cell apoptosis. In vitro cultured Colon26 cells were resistant to TRAIL but susceptible to the combination of IFN-gamma and TRAIL in a TRAIL-dose-dependent manner. The infusion of lymphocytes from FasL-defective donors reduced the tumor progression, although efficacy was decreased in the TRAIL receptor knockdown tumors but not in wild-type ones, compared with infusion of B6-derived lymphocytes. The findings indicate that GVT activity against subcutaneous colon tumors is efficiently induced by preconditioning with irradiation and allogeneic DLI, and that TRAIL and IFN-gamma act cooperatively in the antitumor effect.     

Functional analysis of PIK3CA gene mutations in human colorectal cancer

Mutations in the PIK3CA gene, which encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been reported in human cancers, including colorectal cancer. Most of the mutations cluster at hotspots within the helical and kinase domains. Whereas H1047R, one of the hotspot mutants, is reported to have elevated lipid kinase activity, the functional consequences of other mutations have not been examined. In this study, we examined the effects of colon cancer-associated PIK3CA mutations on the lipid kinase activity in vitro, activation of the downstream targets Akt and p70S6K in vivo and NIH 3T3-transforming ability. Of eight mutations examined, all showed increased lipid kinase activity compared with wild-type p110alpha. All the mutants strongly activated Akt and p70S6K compared with wild-type p110alpha as determined by immunoblotting using phospho-specific antibodies. These mutants also induced morphologic changes, loss of contact inhibition, and anchorage-independent growth of NIH 3T3 cells. The hotspot mutations examined in this study, E542K, E545K, and H1047R, all had high enzymatic and transforming activities. These results show that almost all the colon cancer-associated PIK3CA mutations are functionally active so that they are likely to be involved in carcinogenesis.