齋藤 信也

A retrospective study was carried out in 110 cadaveric kidney transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (AZP) and steroids (triple-drug therapy) with those of higher doses of steroids plus AZP (conventional immunosuppression). Graft survival rate in the triple-drug therapy was 77%, 69%, and 69% at 1, 3, and 5 years, respectively. This was significantly better than 48%, 34%, and 29% in conventional immunosuppression. The incidence of acute rejection episodes was significantly lower in the triple-drug therapy than in conventional immunosuppression (25% vs 58%). In conclusion, our study shows that triple-drug therapy using low-dose cyclosporine is the safest of the immunosuppressive regimens and provides a beneficial effect on the long-term survival of cadaveric kidney transplants.

One-hundred-nine HLA-haploidentical living related renal transplants have been retrospectively analysed to compare the effect of donor-specific blood transfusion (DST) and different immunosuppressive regimens on graft survival and acute rejection. The recipients were divided into four groups according to the immunosuppressive therapy. Group 1 (n = 44): conventional therapy with posttransplant azathioprine (AZP) + methylprednisolone (MP). Group 2 (n = 25): pretransplant DST + posttransplant AZP + MP. Group 3 (n = 12): triple-drug therapy with posttransplant AZP + MP + cyclosporine (CS). Group 4 (n = 25): pretransplant DST + posttransplant AZP + MP + CS. The five-year actuarial survival rates for groups 1, 2, 3 and 4 were 48%, 73%, 79%, and 89%, respectively. The graft survival rate in group 3 was significantly (p less than 0.01) better than that in group 1. The transfusion effect was reduced, and appears as a 10% improvement in the graft survival in the cyclosporin era compared with a 25% improvement at pre-cyclosporin era. Furthermore, the incidence of the first rejection episode was decreased in recipients that received DST. The present study revealed that DST, as pretransplant conditioning has a definite impact on rejection-free long-term graft survival in HLA-haploidentical living-related kidney recipients and the most favorable outcome in such patients could be achieved by DST pretreatment in conjunction with posttransplant triple-drug therapy including cyclosporine.

An artificial liver support system for plasma exchange and plasma perfusion through BR-601 resin using a membrane separator was applied to 5 patients with postoperative liver failure. Percent absorption of total and direct bilirubin, and of bile acids were 77.1 +/- 6.4, 78.4 +/- 6.1, and 93.4 +/- 3.6%, respectively, when 250 ml of plasma was treated. Percent reductions in total and direct bilirubin, and in bile acids were 24.5 +/- 5.8, 25.5 +/- 5.8 and 30.9 +/- 8.5%, respectively. In contrast, percent reductions in total and direct bilirubin, and in bile acids by plasma exchange were 30.9 +/- 13.3, 34.5 +/- 12.5 and 24.2 +/- 8.5%, respectively. The coma grade was improved in 4 out of 5 cases, but unfortunately the patients did not recover. In conclusion, plasma perfusion through BR-601 resin is expected to play a promising role in artificial liver support systems because of its capacity to absorb bilirubin and bile acids.

Three cases of successful pregnancies in renal transplant recipients who had undergone transplantation in the Okayama University Medical School Hospital are reported. Two of the women had received an organ from a living relative and one woman received a cadaveric organ graft. These patients, aged 28-37 at the time of the delivery, had received their transplants 2-5 years prior to their conception. The periods of gestation ranged between 35 and 40 weeks. The weight of the babies at birth ranged from 2,380g to 2,500g and the apgar score at 1 min was 8 or 9. None of the infants showed any congenital abnormalities. Lower-segment cesarean section was performed in all of three cases. Serum creatinine levels, an indicator of renal graft function, did not deteriorate during the pregnancy or after delivery. Although further work is needed to solve problems regarding pregnancy in renal transplant recipients, these results encouraged us to meet their hope for a baby.

POSSUM, a Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity, is a scoring system which assesses perioperative surgical risks (Copeland GP et al.: Br J Surg, 1991, Vol 78, 356-360). The POSSUM scoring system consists of two categories of assessment to assess the risk of surgery. A 12-factor (age, cardiac status, pulse rate, systolic blood pressure, respiratory status, Glasgow Coma Score, serum concentration of urea, potassium and sodium, hemoglobin concentration, white cell count and findings on electrocardiography) and 4-grade physiological score (PS) were developed. This was combined with a 6-factor (type of surgical procedure, number of procedures, blood loss, peritoneal soiling, presence of malignancy and mode of surgery) and 4-grade operative severity score (OSS). The present paper attempts to validate it retrospectively. Postoperative hospitalization period and duration of antibiotics administration were both significantly correlated with OSS, but not with PS. These results suggest that the POSSUM scoring system is useful for predicting the postoperative clinical course.

The antidonor immune response was examined in a one haplotype-mismatched renal transplant recipient with an allograft that had been well-functioning for more than 10 years. Although the relative response of the mixed lymphocyte reaction (MLR) was (45.8)% and the MLR responder cells stimulated by donor cells produced measurable amounts of interleukin-2 (IL-2) (11.6 U/ml), the cytotoxic T lymphocytes (CTL) could not be generated against donor cells, even with exogenous IL-2. These results indicate that antidonor CTL precursors were either deleted or inactivated in this recipient.

Activation of inflammatory response during cardiopulmonary bypass (CPB) may lead to considerable post-operative mortality. Recently, pentoxifylline (PTX), a methylxanthine derivative, has been reported to be effective in inhibiting proinflammatory cytokine production. This study aimed to determine whether or not PTX prevented CPB-induced systemic inflammatory response syndrome (SIRS) in patients undergoing cardiovascular surgery. Thirty adult patients were randomly separated into 2 experimental groups and 1 control group of 10 patients each. The experimental group received peroral PTX administration (Group 1: 600 mg/day, Group 2: 900 mg/day), while the control group did not. In Group 1 and Group 2, PTX administration was started on preoperative day 5 and continued for 5 days. Serum levels of PTX and IL-6 were measured just before and at 4 h after CPB using HPLC and ELISA, respectively. Respiratory index (RI) before and at 4 h after CPB was calculated, and serum levels of C-reactive protein (CRP) and fibrinogen on postoperative day 1 were also determined. There were no significant differences in age, body weight, sex, surgical procedures, CPB time, haemodynamics or risk factors among the 3 groups. Serum IL-6 level and RI index after CPB in Group 2 were significantly decreased compared with those in Group 1 and the control group. These results, therefore, suggested that preoperative daily administration of 900 mg/day PTX contributed to the attenuation of CPB-induced SIRS and had a beneficial effect on the postoperative course after cardiovascular surgery.

Plasma 5-hydroxytryptamine (serotonin), tryptophan, neopterin and cortisol levels were measured in patients with depressive cancer cachexia and in healthy controls during the same time period. Patients with advanced cancers had significantly raised neopterin, a marker of endogenous gamma-interferon (IFN-γ) production, and cortisol values, but decreased serotonin and tryptophan levels. Much work has been done to elucidate the possible role of serotonin in depressive states. IFN-γ induces a high level of indoleamine dioxygenase (IDO), a tryptophan degrading enzyme, and high cortisol levels induce high tryptophan oxygenase activity, which in turn increases metabolism along the tryptophannicotinic acid pathway. These results suggest that persistent immune activation and intense adrenal activity occur in patients with cancer cachexia, resulting in disorders involving tryptophan metabolism followed by depression in cancer cahexia.