Clinical utility of monitoring sialyl Lewis(X) (CD15S) antigen on peripheral lymphocytes for the diagnosis and treatment of rejection after renal transplantation

BACKGROUND: In organ transplantation, the grafts must be carefully monitored, but it is often difficult to make a quick and accurate diagnosis of unusual changes. Extensive research has failed to identify a useful marker for rejection. We investigated the clinical utility of sialyl Lewis(X) (CD15s) monitoring in 17 renal transplant patients with acute rejection. METHODS: The expression of CD15s on peripheral lymphocytes was examined using flow cytometry in renal transplant recipients with rejection (n=17), without rejection (n=23), recipients infected with cytomegalovirus (n=7), recipients with other diseases (n=7), and healthy volunteers (n=18). CD15s expression was compared with histological findings, and was also examined before and after steroid pulse therapy to investigate the effects of steroids on CD15s antigen expression on the surface of the peripheral lymphocytes. RESULTS: CD15s was strongly expressed in all patients with rejection, but was not expressed in any of the patients without rejection or in any healthy volunteers. Histologically, cell infiltration into the rejected graft was moderate or severe in all patients with strong expression of CD15s. In contrast, no or only mild infiltration was observed in patients with weak expression of CD15s. In addition, 14 of 17 patients (14/17, 82%) with strong CD15s expression improved upon administration of steroid pulse therapy, although there was no benefit from steroids in any of the patients with weak expression of CD15s. CONCLUSIONS: The CD15s antigen is expressed strongly on the peripheral lymphocytes at the time of rejection. It is interesting that the efficacy of steroid therapy in the patients with elevated creatinine could be predicted by CD15s expression on the peripheral lymphocytes before graft biopsy. There have been only few reports showing the relationship between CD markers and the efficacy of the treatment in patients with elevated creatinine. We report that the detection of CD15s on the peripheral lymphocytes by flow cytometry was an easy, helpful, and noninvasive means for the diagnosis and treatment of patients with elevated creatinine after renal transplantation.     

Early increased chemokine expression and production in murine allogeneic skin grafts is mediated by natural killer cells

BACKGROUND: Increased expression of chemokine mRNA is observed in allogeneic but not syngeneic skin grafts 3-4 days after transplantation. The recipient cells mediating this early inflammatory response in allografts remain unidentified. METHODS: Isogeneic and allogeneic skin grafts were transplanted to euthymic and athymic nude mice. mRNA expression and protein production of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and the murine homolog of Gro(alpha), i.e. KC, from graft homogenates retrieved 3-4 days posttransplantation was tested by Northern blot hybridization and ELISA. To deplete NK cells, recipients were treated with antiasialo GM1 (ASGM1) antisera or with anti-NK1.1 mAb before transplantation. RESULTS: Expression of KC, MIP-1alpha, and MIP-1beta mRNA was equivalent in C57BL/6 allogeneic skin grafts and BALB/c isografts at day 2 posttransplant. At day 3 posttransplant, chemokine mRNA levels decreased in isografts but were maintained at high levels in the allografts. Increased early chemokine mRNA was also observed in C57BL/6, but not BALB/c++ grafts on BALB/c athymi(nu/nu) recipients. Treatment of allograft recipients with ASGM1 or with anti-NK1.1 antibody eliminated NK cells from the spleen and allograft infiltrating cell populations and decreased early chemokine mRNA levels in allografts 60-70%. Analyses of allograft homogenates indicated increased levels of KC, MIP-1alpha, and MIP-1beta protein at day 4 posttransplant that were decreased in recipients depleted of NK cells. Early chemokine mRNA levels were equivalent in isogeneic and semiallogeneic F1 grafts. CONCLUSIONS: Early chemokine mRNA expression and protein production in allogeneic skin grafts is amplified by recipient natural killer (NK) cells. These results indicate a novel function for infiltrating NK cells in mediating early increased intra-allograft chemokine production and inflammation during the initiation of acute rejection.     

Phase II study of continuous-infusion high-dose ifosfamide in advanced and/or metastatic pretreated soft tissue sarcomas

Background: Ifosfamide has important activity in pretreated soft tissue sarcomas (STS), and recent data support a clinically significant dose-response relationship for this agent. Administration by continuous infusion and hematopoietic support have rendered dose intensification regimens possible by reducing both hematologic and non-hematologic toxicities. The optimal dose and schedule of ifosfamide when given at high doses remain to be defined. In a previous phase I study, we demonstrated the feasibility of a continuous infusion (c.i.) high-dose ifosfamide (HDI) regimen in the ambulatory setting for patients with advanced solid tumors. The objective of the present phase II study was to assess the antitumor activity and toxicity of such a schedule in patients with advanced pretreated STS.Patients and methods: Thirty-eight patients with advanced and/or metastatic STS, all pretreated with an anthracycline with or without standard-dose ifosfamide, were treated. Ifosfamide was given by c.i. at a dose of 3.5 g/m²/day over four consecutive days, with equidose mesna uroprotection over five days. G-CSF was added at a dose of 200 µg/m²/day subcutaneously from day 6 to day 12. Cycles were repeated every three weeks in the outpatient setting.Results: A total of 159 cycles of therapy were given (median 4 per patient, range 3–6). Treatment compliance was generally satisfactory. The major toxicity was hematologic, with six febrile neutropenic episodes requiring hospitalisation and parenteral antibiotics. Acute renal failure occurred in one patient after three cycles of therapy; central nervous system toxicity was mild. An overall response rate of 39% was observed (95% confidence interval, 26% to 55%), with one complete and 14 partial remissions. All but one of the responder patients had previously received standard-dose ifosfamide. The median response duration was nine months (range 5–21+ months), and the overall median survival ranged from 6–30+ months (median 13 months).Conclusions: High-dose ifosfamide is an active regimen in anthracycline- pretreated STS. Future clinical trials should be aimed at evaluating the impact of different administration schedules on clinical response and outcome. The potential role of HDI as front-line chemotherapy as well as in the adjuvant treatment of STS needs to be investigated in randomized trials.     

Endoscopic stapled diverticulotomy: a real advance in the treatment of hypopharyngeal diverticulum

Between November 1993 and May 1996, 51 patients with a hypopharyngeal diverticulum were treated by endoscopic stapled diverticulotomy. Normal swallowing was resumed within 36 h of surgery in 73%, and in 93% by 72 h. Two patients required nasogastric feeding for 5–7 days. There were no operative deaths or serious operative morbidity, and there have been no recorded cases of clinical recurrence of pouches to date (maximum follow-up 562 days: 46 cases over 12 months). The low morbidity, short hospital stay and early return to normal feeding, combined with a relative absence of complications or pouch recurrence, make endoscopic stapled diverticulotomy the treatment of choice for the majority of patients.     

Supramolecular chemistry and technology

Supramolecular chemistry deals with the association of several chemical species, in an organized way and according to well defined purposes. Based on a molecular engineering approach, supramolecular structures can be designed from pre-formed building blocks, providing a promising route from chemistry to molecular nanotechnology. New supramolecular systems have been assembled in our laboratory with the use of bridging unities such as tetrapyridylporphyrins, porphyrazines and polypyrazines, connecting transition metal complexes and clusters. These systems display a very exciting electrochemical and catalytic behavior, and interact with DNA, generating 1O2 and leading to efficient oxidative clivage for photodynamic terapy applications. Molecular interfaces have been developed, exhibiting photocurrent response in the presence of visible-UV light, and rectifying properties in the presence of electroactive species. Successful applications of the supramolecular species in chemical and bio-sensors have been developed.     

A case of emphysematous pyelonephritis improved with conservative therapy--indication for conservative therapy

A 51-year-old female patient was hospitalized in our department with high fever and left flank pain. Laboratory examination showed leukocytosis, increase of C-reactive protein (CRP), hyperglycemia and renal insufficiency. Enterobacter aerogenes grew out of the cultured urine. The radiograph and computerized tomographic (CT) scan revealed streaky gas in the destroyed left renal parenchyma with perirenal gas. She was diagnosed with left emphysematous pyelonephritis. Antibiotics therapy, treatment for sepsis and disseminated intravesicular coagulation was initiated resulting in mitigation of inflammation. High blood glucose initially required insulin therapy, but finally returned to normal levels through administration of oral antidiabetics. Although leukocytosis and low grade fever continued, the patient was discharged on day 53 with a negative CRP. CT scan indicated that the emphysematous change was localized after three months and almost resolved after four months. Renal scintigram indicated the residual function of the affected kidney. Because of the possibility of residual renal function and the cure by conservative therapy alone, the conservative therapy is preferred when the initial treatment is effective.