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1.
H. Isoniemi J. Ahonen B. Eklund K. Höckerstedt K. Salmela E. von Willebrand P. Häyry 《Transplant international》1990,3(2):92-97
We have investigated the impact of triple drug immunosuppression on the occurrence of early inflammatory episodes, as detected by fine needle aspiration biopsy, and of episodes of clinical rejection during the immediate postoperative period. The prospective component of this study includes 128 consecutive first cadaveric renal transplant recipients receiving triple drug treatment consisting of azathioprine (Aza), cyclosporin (CyA) and methylprednisolone (MP). For controls we have used three historical groups: one immunosuppressed with Aza and MP (group A), another with CyA monotherapy (group B), and the third with CyA together with MP (group C) in equivalent drug dosages. On the average, 0.8 episodes of inflammation per patient were recorded during the immediate postoperative period of 30 days with triple drug treatment. This was significantly less than the 1.3 episodes in patients receiving Aza and MP (P<0.01), the 1.7 episodes in patients on CyA monotherapy (P<0.001), or the 1.6 episodes in patients receiving CyA together with MP (P<0.001). Although the first episode of inflammation commenced concurrently in each group and the peak intensity of inflammation was the same, the mean duration of inflammation was significantly shorter-2.7 days-under triple drug treatment than the 7.8–11.7 days for controls (P<0.001). The frequency of rejection episodes under triple treatment was also significantly lower-0.2 per patient-than the 0.8 per patient in controls (P<0.001). The first rejection episode occurred later in the triple drug treatment group-on the average, on day 15.2-than in the historical controls (on days 7.7–11.7). There was, however, no difference in the duration of rejection. There were no differences in patient survival between the four groups. Graft survival was 97% at 10 weeks for triple drug-treated recipients and 79%, 68%, and 87% for first grafts in groups A, B, and C, respectively. Disregarding a minor demographic bias for the triple drugtreated group with respect to preformed antibodies and preoperative dialysis treatment, the study suggests that the triple drug protocol, in the short run, is superior to any conceivable double drug combination or CyA monotherapy. 相似文献
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At our center, since 1982, a body mass index (BMI) of less than 30 has been a prerequisite for placing a patient on the waiting
list for renal transplantation. This decision was made because obese transplant recipients seemed to have a less than favorable
post-transplant outcome. The aim of this study was to evaluate whether this requirement is still justified. Forty-six patients
with a BMI above 30 underwent primary cadaveric renal transplantation between 1972 and 1993. For each of these obese patients,
five consecutive non-obese (BMI 20–25) control patients were selected. Patient and graft survival, causes of graft loss, and
acute rejection rate were evaluated for the two patient groups before and after the year 1982. Within the first 30 post-transplant
days, one patient (2 %) and 11 grafts (24 %) were lost in the group of obese patients whereas seven patients (3 %) and 36
grafts (16 %) were lost in the control group. Among the obese patients, renal circulatory complications were a major cause
of graft loss. In the period 1973–1981, the 1-year patient survival rate was 65 % among obese patients versus 75 % among controls
from 1982 to 1993, this was 90 % versus 93 %. From 1973 to 1981, the 1-year graft survival rate was 25 % among obese patients
versus 53 % among controls (P < 0.05); from 1982 to 1993, it was 68 % versus 84 % (P = NS). Multivariate analysis showed that the immunosuppressive regimen,
age of the patient, BMI, and cold ischemia time of the graft had a significant influence on graft survival. The acute rejection
rate within the first 30 days was 28 % among obese patients and 35 % among controls (P = NS). We conclude that a BMI below
or equal to 30 is still justified as a prerequisite for placement on the waiting list for renal transplantation, for despite
an overall improvement, the outcome of renal transplantation in obese patients remains worse than that in non-obese patients.
Received: 3 February 1997 Received after revision: 4 April 1997 Accepted: 8 April 1997 相似文献
5.
H. Isoniemi J. Ahonen B. Eklund K. Höckerstedt K. Salmela E. von Willebrand P. Häyry 《Transplant international》1990,3(1):121-127
Abstract. A prospective randomized study was conducted to evaluate the impact of four different conversion protocols on graft outcome in long-term follow-up. Between January 1986 and May 1987, 128 patients with first cadaveric kidney allografts were randomized at the time of transplantation to four treatment groups of 32 patients each, to be assigned 10 weeks post-transplantation. During the first 10 weeks, all patients received triple therapy with low-dose azathioprine (Aza), cyclosporin (CyA), and methylprednisolone (MP). After 10 weeks, one group continued with triple therapy (group A) while the three other groups received different combinations of two drugs, namely, Aza and CyA (group B), Aza and MP (group C), or CyA and MP (group D). Withdrawal of MP (group B) or especially of CyA (group C) was associated with 4/29 (14%) and 10/28 (36%) acute rejection episodes, respectively, for 60 days after conversion. All rejections were mild and reversible. There were no rejections after Aza withdrawal or in the group that continued on triple therapy during the corresponding time period. The most common reason for dropping out after withdrawal, for those patients who could not continue on the originally randomized medication, was azathioprine intolerance (n= 12). Five patients were switched back to triple therapy after CyA withdrawal due to rejection. Steroid intolerance was rare and CyA in low doses was very well tolerated. At 1 year there were no statistically significant differences in graft survival between groups A, B, C, and D-81 %, 88%, 88%, and 88%, respectively-or in patient survival-88%, 88%, 88%, and 97%, respectively. For those patients continuing with the originally randomized treatment protocol, there were no differences in patient or graft survival either, the means being 91% and 89%, respectively. The most common cause of death after withdrawal was cardiovascular in nature, and there were no more fatal infections under triple drug treatment than with double drug regimens. There were no statistically significant differences in mean serum creatinine values at 1 year. The median serum creatinine values for groups A, B, C, and D were 112, 132, 133, and 133 μmol/l, respectively. At 1 year the mean CyA dose in the groups that continued with CyA was 3. 5–4. 2 mg/kg per day and CyA concentrations were equal. 相似文献
6.
Characterization of nephropathy induced by immunization with high molecular weight dextran 总被引:1,自引:0,他引:1
Pasi A; Dendorfer U; Holthofer H; Nelson P; Tazzari S; Armelloni S; Fornasieri A; D'Amico G; Schlondorff D 《Nephrology, dialysis, transplantation》1997,12(9):1849-1855
Background. Injection of DEAE dextran into Lewis rats
can produce proteinuria and has been reported as a model of IgA
nephropathy. Methods. Cationic diethyl aminoethyl
(DEAE) dextran of molecular weight 500 KDa was injected into male Lewis
rats. After a pre-immunization period of 3 weeks, the animals were divided
into two groups: group 1 (n=14) received daily i.v. injections of 3.5 mg of
antigen, group 2 (n=14) was injected with 1.5 mg three times per week for a
total period of 6 weeks. I.v. treatment was initiated with gradually
increasing doses of DEAE dextran in both groups for 1 week, after which the
maintenance dose was reached. Results. We observed the
appearance of proteinuria in a nephrotic range after 5 weeks of i.v.
injections in group 1 (urinary excretion: 332±83 mg/24 h,
controls: 53±14 mg/24 h). In group 2, the proteinuria was almost
equal to protein excretion of healthy rats of the same weight
(67±20 mg/24 h). The serum and urine creatinine were normal. By
light microscopy of kidney biopsies, the presence of focal and segmental
proliferation of mesangial cells after 6 weeks of i.v. injections was
identified. Immunohistochemistry revealed no deposition of IgA, IgM, IgG,
or C3. Using anti-ED1 antibodies, there was no evidence of interstitial
infiltration of monocytes/macrophages after 6 weeks of i.v. injections.
Staining for proliferating cell nuclear antigen (PCNA) did not show the
presence of proliferating cells either in glomeruli or in the interstitium.
Staining with FITC-WGA lectin revealed focal and segmental loss of the
negative charge in the capillary wall. By electron microscopy there was
deposition of dextran in the basal membrane and segmental and focal damage
of the podocyte foot processes. As the chemokine RANTES may be involved in
glomerular injury, we examined the kidneys of proteinuric and
non-proteinuric rats for the presence of RANTES. By indirect
immunofluorescence only the proteinuric rats showed RANTES deposition in
mesangium. Conclusions. Injection of rats with DEAE
dextran leads to dose-dependent proteinuria without deposition of immune
complexes but with podocyte damage. This is associated with local
expression of the chemokine RANTES which may play a role in proteinuria of
glomerular disease. 相似文献
7.
Neill Booth Antti Jula Pasi Aronen Minna Kaila Timo Klaukka Katriina Kukkonen-Harjula Antti Reunanen Pekka Rissanen Harri Sintonen Marjukka Mäkelä 《BMC health services research》2007,7(1):172
Background
Hypertension is one of the major causes of disease burden affecting the Finnish population. Over the last decade, evidence-based care has emerged to complement other approaches to antihypertensive care, often without health economic assessment of its costs and effects. This study looks at the extent to which changes proposed by the 2002 Finnish evidence-based Current Care Guidelines concerning the prevention, diagnosis, and treatment of hypertension (the ACCG scenario) can be considered cost-effective when compared to modelled prior clinical practice (the PCP scenario). 相似文献8.
Arto J. Turunen José A. Fernández Leena Lindgren Kaija T. Salmela Lauri E. Kyllönen Heikki Mäkisalo John H. Griffin Sanna M. Siitonen Jari Petäjä Eero J. Pesonen 《American journal of transplantation》2005,5(9):2204-2212
We studied the role of endogenous activated protein C (APC), the major physiological anti-coagulant with concomitant anti-inflammatory properties, on ischemia/reperfusion (I/R) in 45 patients participating in a larger trial comparing three immunosuppressive protocols in cadaveric renal transplantation: perioperative anti-thymocyte globulin (ATG, Fresenius AG, Bad Homburg, Germany), perioperative basiliximab and conventional triple therapy. Blood samples for assessing plasma APC, protein C, and lactoferrin concentrations, neutrophil CD11b and L-selectin expressions and blood leukocyte differential counts were obtained preoperatively and before reperfusion from central venous cannula, complemented with simultaneous samples from iliac artery and graft vein for calculation of transrenal differences (Delta) of study parameters at 1 and 5 min after reperfusion. Unlike basiliximab or conventional therapy groups, ATG infusion induced a substantial increase in plasma APC concentration (119 [88-144]% before infusion vs. 232 [85-1246]% after infusion, p<0.001), resulting in renal graft sequestration of APC at 1 min after reperfusion (Delta=-72 [-567 to 12]%, p<0.001). Graft APC consumption was associated with transrenal reduction of neutrophil activation markers (L-selectin r=0.7, p=0.01; lactoferrin r=-0.6, p=0.02; CD11b r=-0.8, p=0.001), and with both warm (r=0.6, p=0.01) and cold ischemia time (r=0.6, p=0.02) and donor age (r=0.6, p=0.01). These findings suggest that APC has an anti-inflammatory role in I/R injury in clinical renal transplantation. 相似文献
9.
Acute IP injection of benzyl alcohol but not benzaldehyde (0.5 g/kg) caused aversion to voluntary drinking of 5% ethanol solution by male rats with preference to ethanol. Benzyl alcohol noncompetitively inhibited hepatic alcohol dehydrogenase of rats maintained for a short term on 5% ethanol compared to control. The results suggest an adverse interaction between benzyl alcohol and ethanol underlying the observed aversion to ethanol. 相似文献
10.