Interstitial and vascular pancreas rejection in relation to graft survival

To examine the incidence of interstitial and vascular rejection in pancreas allografts and its impact on graft survival, we studied 36 percutaneous pancreas biopsies and 10 pancreas transplantectomy specimens from 32 patients who had undergone simultaneous pancreas-kidney transplantation. Interstitial rejection (IR) was predominantly found in the biopsies, while vascular rejection (VR) was most prominent in the transplantectomies. Pancreas graft survival was significantly decreased for pancreas grafts that had suffered from vascular rejection when compared to those with only interstitial rejection. Potential rejection markers, i. e., serum amylase, glucose, creatinine, and urinary amylase, did not correlate with histological signs of rejection, although increased levels of serum amylase were, in all but one case, associated with rejection.We conclude that a percutaneous pancreas biopsy remains the most reliable method to determine pancreas rejection, and that by distinguishing between IR andVR, a pancreas biopsy may provide important diagnostic as well as prognostic information. Received: 6 March 1997 Received after revision: 5 June 1997 Accepted: 30 June 1997     

Patient survival after renal transplantation; more than 25 years follow-up

Background: The determinators of patient survival after renal transplantation are incompletely known, and conflicting results hae been reported. This may have been influenced by time-related changes in patients selection, post-transplantation management and immunosuppressive regimens. This study was performed to evaluate in recipients of a first renal transplant the effect of patient characteristics, transplantation era, and the immunosuppressive regimen on patient survival. Method: We studied data from the Leiden Renal Transplant Database of all first renal transplantations performed between 1966 and 1994 in Leiden, the Netherlands. The effect of the following parameters on mortality was investigated: era of transplantation, sex, age at transplantation, cause of renal failure, immunosuppressive regimen, type and duration of pretransplantation dialysis, hypertension, diabetes mellitus, and smoking. In addition we analysed the causes of death. Results were expressed as crude mortality rates, relative risks of mortality, and standardized mortality ratios as compared with death rates in the Dutch population. Results: The analysis comprised 86 living donor transplant recipients and 916 cadaver transplant recipients. After adjustment for age and sex, the relative risk of morality for living donor transplant recipients compared with cadaver transplant recipients was 0.5 (95% CI 0.2 to 10.3, P=0.06). In the first cadaver kidney transplant recipients the risk of first-year mortality improved significantly with time, which coincided with the introduction of cyclosporin. The risk of mortality after the first year was higher in patients aged over 40 years at transplantation, men, smokers, and in the presence of hypertension or diabetes, but the effect of individual factors on mortality was small. We found no effect of the type of pretransplantation dialysis or the duration of pretransplantation haemodialysis on post-transplantation mortality. The standardized mortality ratio for recipients of first renal transplants was 14 times the population average in the first year after transplantation and was still four times in the remaining years. Conclusion: In the present study, time-related changes in patient management were responsible for improved patient survival in the first year after transplantation during the study period. Many individual factors contributed moderately to the risk of mortality after the first year. Compared to the general population the mortality rate of renal transplant recipients was significantly higher during the whole follow-up period.     

Magnetic resonance relaxation times of normal tissue in the course of chemotherapy: a study in patients with bone sarcoma

To study the effect of chemotherapy on normal fat, skeletal muscle, and bone marrow, T1 and T2 relaxation times were measured in 15 patients with bone sarcoma before and after each cycle of preoperative chemotherapy. A section plane containing the tumor and if possible the nonaffected extremity was imaged with combined multiecho spin echo and inversion recovery pulse sequences. T1 and T2 relaxation times were calculated in the normal-appearing tissues. Although some variation was found in the values in the individual patient and between patients, no systematic changes of relaxation times of fat, muscle, or bone marrow occurred in the course of treatment. We conclude that the chemotherapy used in bone sarcoma has no effect on relaxation times of normal fat, muscle, and bone marrow, and that therefore these tissues may serve as a reference for the signal intensity of tumor.     

The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity.

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly reduced in CHO+NQO1 cells compared to wild-type CHO cells, validating the NQO1-overexpression in the CHO+NQO1 transfectant. Quercetin inhibited the proliferation of wild-type CHO and CHO+NQO1 cells to a similar extent without affecting cell viability, indicating that NQO1 enrichment of CHO cells did not provide increased protection. On the other hand, inhibition of NQO1 in both types of cells by dicoumarol significantly potentiated the inhibitory effect of quercetin on cell proliferation, revealing the role of NQO1 in cellular protection against quercetin. Altogether, these results can be explained by the hypothesis that both wild-type CHO and CHO+NQO1 cells contain sufficient NQO1 activity for optimal protection against the pro-oxidant effect of quercetin on cell proliferation. The results also point at a cellular NQO1 threshold for optimal protection against quercetin. This NQO1 threshold seems to be in the range of NQO1 activities already present in various tissues.     

Taking anti-neutrophil cytoplasmic antibody (ANCA) testing beyond the limits.

The application of anti-neutrophil cytoplasmic antibody (ANCA)testing has received much interest since ANCA were discovered[1] and since they were reported to be useful in both the diagnosisand monitoring of disease activity in Wegener's granulomatosis(WG) [2]. Although there is little doubt that the recognitionof the association between the presence of ANCA and active vasculitishas had a very positive influence on research on the pathogenesisand treatment of ANCA-associated diseases (reviewed by Savage[3]), there are reasons to worry about the application of thisrecently gained knowledge in clinical practice. In this commentthe problems with the clinical application of ANCA tests arecategorized for the sake of clarity as (i) standardization problems,(ii) difficulties with application of the test in the appropriate     

Production of fimbrial adhesins K99 and F41 by enterotoxigenic Escherichia coli as a function of growth-rate domain.

The production of fimbrial adhesins K99 and F41 by enterotoxigenic Escherichia coli has been measured in steady-state chemostat experiments at various specific growth rates (microseconds) and in a recycling fermentor across a range of mu values falling to less than 0.004 h-1. It has been demonstrated that the production of K99 and F41 fimbriae is correlated with mu both in aerobic and anaerobic chemostat experiments. A significant production of fimbriae was only detected at mu values higher than 0.2 h-1. This behavior was further examined by culturing the bacteria in a recycling fermentor with complete biomass retention. It could be shown that the production of K99 and F41 fimbriae only occurred during balanced growth, with a high biomass yield at mu values higher than 0.04 h-1 corresponding to mass doubling times (td) of less than 17 h. The production of both fimbriae halted during balanced growth with a lower biomass yield (at mu values between 0.012 and 0.04 h-1 corresponding to td values between 17 and 58 h) and unbalanced stringent growth (at mu values lower than 0.012 h-1 or td values higher than 58 h). The external pH of the medium greatly influenced the production of both K99 and F41 fimbriae. At pH values lower than 7, the production of fimbriae was strongly inhibited. Also, at pH values higher than 7, a decrease in production was observed. The consequences of the observed phenomena for the pathogenic behavior of this E. coli strain are discussed.     

Reticuloendothelial Fc receptor function in SLE patients. I. Primary HLA linked defect or acquired dysfunction secondary to disease activity?

Reticuloendothelial system (RES) Fc receptor-mediated immune clearance was measured in 18 patients with systemic lupus erythematosus (SLE). Only two patients, with major disease activity, had a prolonged T 1/2 of the blood disappearance curve of injected IgG coated red cells in comparison to 22 healthy controls. Circulating immune complexes (CIC) were studied with three methods: PEG precipitation, C1q-ELISA and the indirect granulocyte phagocytosis test (IGFT). The T 1/2 of the blood disappearance curve related significantly to the IGFT (r = 0.55, P less than 0.05) and not to the PEG and C1q-ELISA test. Although HLA-DR3 phenotype frequency was significantly increased in our SLE population (P less than 0.05), it was not related to Fc receptor function. Similarly, HLA-DR2 phenotype was not related to RES Fc receptor function. These data do not support the concept that a genetic HLA linked defect in reticuloendothelial Fc receptor function is a primary cause of SLE, predisposing the inflicted individual to immune complex deposition. However, Fc receptor-mediated immune clearance seems to be related to disease activity itself and to levels of CIC.     

Optimum cycle frequencies in hand-rim wheelchair propulsion

Summary To study the effect of different cycle frequencies on cardio-respiratory responses and propulsion technique in hand-rim wheelchair propulsion, experienced wheelchair sportsmen (WS group; n=6) and non-wheel chair users (NW group; n=6) performed wheelchair exercise tests on a motor-driven treadmill. The WS group wheeled at velocities of 0.55, 0.83, 1.11 and 1.39 m · s^–1 and a slope of 2°. The NW group wheeled at 0.83, 1.11 and 1.39 m · s^–1 and a 1° slope. In each test, a 3-min period at a freely chosen cycle frequency (FCF: 100%) was followed by four 3-min blocks of paced cycle frequencies at 60%, 80%, 120% and 140% FCF. Effects of both cycle frequency and velocity on physiological and propulsion technique parameters were studied.Analysis of variance showed a significant effect (p<0.05) of cycle frequency on oxygen cost and gross mechanical efficiency in both the WS and NW group. This indicated the existence of an optimum cycle frequency which is close to the FCF at any given velocity. The optimum cycle frequency increased with velocity from 0.67 to 1.03 cps over the range studied (p< 0.05). Oxygen cost was 10% less at 100% FCF than at 60% or 140% FCF. Gross mechanical efficiency for the WS group at 100% FCF was 8.5%, 9.7%, 10.4% and 10.1%, respectively, at the four velocities. The similarity in the trend of oxygen cost and gross mechanical efficiency data in both the WS and NW groups suggests that an optimum cycle frequency is not merely a consequence of practice alone, but also reflects a physiologically determined optimum, dependent on muscle mechanics, e.g. velocity of contraction and power output of the muscles used.