Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans.

We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.     

Measures of Explained Variation for a Regression Model Used in Survival Analysis

This paper describes a measure of explained variation (MEV) of survival times for a given regression model used in survival analysis. It quantifies the predictive power of a set of prognostic factors in the model, and therefore provides useful information for more precise prediction of patient prognosis, and for designing randomized clinical trials with the capability of determining treatment effects. The MEV defined in this article is asymptotically derived from the squared product-moment correlation; it can be interpreted as an adaptation of the multiple correlation coefficient for the normal linear model to the survival time regression model. Monte-Carlo simulations are performed to investigate the statistical behavior of the proposed MEV. The MEV is applied to estimate the predictive power of several sets of prognostic factors for gastric cancer in Japan using data from a large clinical trial.     

A case of recurrent gastric cancer successfully treated with a combination of cisplatin and carmofur

A 51-year-old man with recurrent gastric cancer was treated by combined administration of Cisplatin and Carmofur. The target sites were the abdominal lymph nodes and the area of invasion to the stomach. Cisplatin (50 mg/body/day) was given for 3 days, while Carmofur (400-800 mg/body/day) was administered daily in 1 course. After 1 course of administration, the target tumor was reduced in size and the therapy was continued. A complete response was confirmed by upper gastrointestinal roentgenography, endoscopy and echography after 8 courses of Cisplatin administration. The patient has survived for 2 years 6 months in a state of CR. This case suggests that a combination therapy of Cisplatin and Fluoropyrimidine derivatives might be effective for gastric cancer.     

Long-term results of open reduction for residual subluxation in congenital dislocation of the hip: A new open reduction method involving 360° circumferential capsulotomy

We report satisfactory results with a new operative treatment, conducted via an extensive anterolateral approach, involving 360 degree circumferential capsulotomy, for residual subluxation in congenital dislocation of the hip (CDH). Long-term radiographic results of this procedure (group A) were compared retrospectively with the results of partial capsulotomy (group B), which preserved the posteroinferior joint capsule. The mean center edge angle in group A (22.5°) was greater than that in group B (16.0°). Satisfactory results were achieved in 11 of 15 hips (73%) (Severin class I or II) in group A, and in 5 of 12 hips (42%) in group B. These results suggest that whole circumferential capsulotomy can remove obstacles to complete reduction, and that acetabular development can be expected in hips reduced by the procedure, without the performance of innominate osteotomy. We believe that our technique is a useful alternative for the treatment of residual subluxation in CDH.     

An analysis of subretinal fluid in bullous retinal detachment

A patient with bilateral bullous retinal detachment underwent drainage of the subretinal fluid. The analysis of the subretinal fluid revealed a high protein concentration--17.4 g/dl OD, 27.5 g/dl OS--which was 3-5 times higher than that of the patient's serum. The protein fractionations of the subretinal fluid were almost the same as those of the serum. These findings may well explain the shifting fluid and support the theory that bullous retinal detachment is caused by the breakdown of retinal pigment epithelial function as a barrier between the choroid and retina.     

Fecal stream is essential for adaptive induction of glucose-coupled sodium transport in the remnant ileum after total proctocolectomy

Our previous studies demonstrated that sodium glucose cotransporter 1 (SGLT-1) was induced in the remnant ileum of total colectomized rats via the action of factors other than hyperaldosteronism. The aim of the present study was to clarify whether fecal stream is required for the enhancement of SGLT-1-mediated sodium transport. Twenty-seven pairs of ileal tissues were obtained from the proximal and distal side, respectively, of loop ileostomy after total proctocolectomy. Mucosae were mounted in an Ussing chamber to evaluate glucose-coupled sodium transport. Levels of SGLT-1 mRNA in proximal and distal mucosae were compared by Northern blotting. Villous height and crypt depth were measured to test for correlations between mucosal structure and SGLT-1-mediated sodium transport or mRNA expression levels. Both glucose-coupled sodium transport and expression of SGLT-1 mRNA were significantly lower in distal mucosae relative to proximal mucosae. In distal mucosae, villous height, but not crypt depth, was significantly lower than in proximal mucosae, demonstrating a positive correlation between villous height and SGLT-1 function and expression. Comparative studies of proximal and distal mucosae demonstrated that in addition to hormonal changes, fecal stream is required for full induction of the sodium transport system (which includes SGLT-1-mediated transport) in the remnant ileum following total proctocolectomy. Presented in part at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–19, 2005 (poster presentation). This work was supported by Grants-in-Aid for Scientific Research 10557118 and 14657295 from the Ministry of Education, Science and Culture of Japan to K. Fukushima, and by Kanae Foundation to K. Fukushima.