Decreased risk of suicide in renal transplant patients on cyclosporin.
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Biomedical subjects
Publications and source records attributed to A Montandon.
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The survival of transplanted cadaver kidneys was compared in a group of 33 first-transplant patients treated with antazoline (Antistine) in addition to conventional immunosuppressive therapy (group A) and a group of 36 patients receiving immunosuppressive therapy only (group B). After 1 year, the transplant survival rate was 79% in group A as compared to 56% in group B (P less than 0.05). The difference which was still present after 2 and 5 years could not be attributed to any other factors that might have influenced the survival rate. Antazoline appears above all to diminish the intensity of moderately severe rejection episodes, which often lead to graft loss inducing a chronic type of rejection reaction. However, the frequency of rejection crises during the first 4 months and the percentages of patients without rejection or with primary irreversible rejection crises were practically the same in the two groups. The mechanism of action underlying this potentially important immunosuppressive effect of antazoline is as yet not clarified.
A multi-centre, randomized double-blind parallel study was carried out to compare the efficacy and tolerance of a single daily dose of controlled-release (CR) capsules of diazepam (10 mg and 15 mg) with placebo under conditions close to those of general practice. All patients between 16 and 60 years of age, presenting an anxiety syndrome as a result of neurotic disturbance, for whom benzodiazepine treatment was indicated for at least 3 weeks, were accepted for the study. The results from 231 patients (119 on placebo, 55 on 10 mg and 57 on 15 mg diazepam) were analyzed after 1 and 3 weeks of treatment. Complaints were found to have improved after 1 week and 3 weeks in the controlled-release diazepam groups whereas the corresponding results with placebo were clearly less favourable. After 1 week, and even more strikingly after 3 weeks, evaluation of the general effects of treatment showed better results with diazepam than with placebo. The obviously higher rate of drop-outs on placebo confirmed its less reliable effect. The controlled-release capsules were well tolerated and notably better than placebo. The most frequent side-effect reported on diazepam was fatigue, and this was probably due to a relative overdosage from use of a standardized dose throughout treatment. Other reported side-effects could not definitely be ascribed to the drug. At the end of a week, successful results were achieved in 48.2% of the patients on controlled-release diazepam compared with only 14.3% of those on placebo. After 3 weeks, these figures were 73.2% and 30.3%, respectively.
The ability of three hollow-fiber dialyzers (Cuprophane [CU], polymethylmethacrylate [PMMA], and polyacrylonitrile [PAN]) to activate complement and to induce leukopenia was studied prospectively in six patients on long-term hemodialysis. CU membranes caused the most intense complement activation with C3a, C3d, and C5a levels peaking 15 min after beginning dialysis. Total white blood cell (WBC) counts dropped simultaneously by 76%, and the decrease in leukocytes was inversely correlated with the levels of C3a and C5a. In contrast, PMMA membranes led only to slight complement activation with an associated fall in WBC counts of 29%, and PAN membranes induced very little complement activation without leukopenia. In vitro studies involving incubation of normal human plasma with each of the three membranes corroborated these findings. The results suggest that the biocompatibility of PMMA and PAN dialyzers is superior to CU.
The present study including 136 cadaver kidney transplants in 119 recipients has shown that the long term function and survival of kidney grafts are closely related to the early immunological reactions of the recipients. Under conventional immunosuppression the most important period for the outcome of the grafts extends to the first 4 months. Not only the number but especially the severity of the early rejection episodes are of prognostic value. Two groups can be distinguished using a classification of severity of early rejection episodes: the first one is characterized by an excellent graft survival and late function (87% one year graft survival) and includes those kidneys with zero or only 1-2 slight early rejection crisis (type 1 and/or 2). In the second group with more than two slight crisis or more severe forms of rejections (type 3 or 4) the one year graft survival is significantly reduced (52%: p less than 0.01). In this group compensatory hypertrophy is usually absent. This is in opposition to the functional improvement of 14 ml/min of GFR after 12 months observed in the patients with good immunological tolerance.
Transient renal glycosuria was observed in eight renal transplant patients during the recovery phase from initial tubular necrosis or acute rejection. In these subjects and three homograft recipients without glycosuria we performed glucose titration experiments. Three patients were found to have type A glycosuria, two had type B and three type C. The titration curve was normal in the three patients without glycosuria. In addition, most subjects presented with hypophosphataemia and hyperphosphaturia. Apart from a direct correlation between the point of splay of the glucose titration curves and the fractional clearance of phosphate, there was no clear-cut relationship between the handling of glucose and phosphorus. Mild hyperchloraemic acidosis was observed in six subjects, but this was unrelated to the type and grade of glycosuria. It is concluded that in homograft recipients the tubular alterations have a patchy and unpredictable distribution and may cause a variety of symptoms which do not necessarily occur in close association.
Since pretransplant blood transfusions have been shown to prolong the survival of kidney grafts, a new transfusion policy has been started in the frame of Swisstransplant. Before surgery all patients receive at least two and, if possible, five transfusions (whole blood or packed red blood cells). The present study includes 101 recipients of primary cadaver grafts. Of these, 41 were transfused regularly according to the new protocol, 46 had irregular transfusions because of therapeutic necessity, and 14 had no transfusion before grafting. The 1-year survival rate in pretransfused patients was over 70% as compared to 45% in the nontransfused group. There was no significant association with the number of transfusions, but a slight improvement in graft survival was seen in patients deliberately transfused when compared with those transfused because of severe anaemia. A delay of more than 3 months between the last transfusion and transplantation significantly decreased graft survival at 6 months (84 versus 58%; P less than 0.02). The occurrence of cytotoxic antibodies, both antiperipheral blood lymphocytes (PBL) and anti-B cell antibodies, was investigated in relation to the number of transfusions received. Broad-spectrum anti-PBL antibodies (greater than 50% of random panel) were found in 5 of 74 patients transfused according to the protocol (7%) and in 15 of 93 patients transfused for severe anaemia (16% P, not significant). Of 71 recipients followed up for 6 months, 15 (21%) produced anti-PBL antibodies with limited specificity (less than 50%), and 4 (6%) produced broad-spectrum antibodies. Anti-B cell antibodies (less than 50%) were produced in 21 of 64 patients (33%). Six patients (9%) had broad-spectrum activity. The occurrence of these antibodies was not associated with the number of transfusions received and did not significantly influence the graft survival at 6 months. The change in transfusion policy seems to have improved graft survival without producing strong presensitization in a prohibitive proportion of the patients on hemodialysis.
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87 patients with end-stage renal failure on long-term hemodialysis, 25 not on dialysis and 37 with renal transplants have been studied. Serum ferritin was measured by immunoradiometric and radioimmuno-assay. The correlation between the two methods was excellent (p less than 0.001). In 25 patients on long-term hemodialysis a good correlation was found between serum ferritin levels and stainable iron (p less than 0.001). All patients with adequate iron stores had serum ferritin levels above 60 ng/ml, whereas only one out of 10 with decreased or absent iron stores had a higher leve (118 ng/ml). According to these criteria the iron stores were decreased in 59% of our patients on long-term hemodialysis, decreased or adequate in 14% and adequate or increased in 27%. There was no correlation between serum ferritin levels and serum iron and total iron binding capacity. The distribution pattern of the serum ferritin levels was log normal and did not significantly differ in the three groups studied, although the patients with renal transplants had nearly normal hemoglobin and creatinine levels. Elevated serum ferritin levels in patients (21%) on hemodialysis could only partly be explained by repeated transfusions or chronic infections.
Early acute rejection with oligo-anuria was observed in 9 cases among 103 cadaver kidney allografts transplanted between January 1969 and May 1977. According to our experience this type of rejection crisis occurs between the 6th and 9th day after transplantation. It is characterized by a typical clinical course. The beginning is acute with high fever and swelling of the graft, followed by oligo-anuria demanding treatment with hemodialysis. In all cases except one there was total restoration of graft function after an oligo-anuric period of 4--16 days. The late prognosis was good in 5 cases. The other 4 patients lost their grafts during the first 4 months after transplantation as a consequence of a second irreversible rejection reaction. The pathogenesis of this early acute and reversible failure of the transplant is discussed, together with the histologic findings in one case.
We have investigated 16 serum proteins in 20 patients with stable renal function after renal transplantation. Our investigations have shown the following substantial findings: a regular increase of prealbumin, alpha1-glycoprotein, haptoglobin, hemopexin and beta2-glycoprotein, as well as a rather frequent increase of alpha 2-macroglobulin. As far as variations of the serum protein levels are concerned there was no correlation with kidney disease, accompanying illnesses, therapy or interval since transplantation.
By means of a photon densitometer utilizing a 125I-source, bone mineral content was measured in 15 chronic renal failure patients on conservative management, 46 patients on maintenance hemodialysis and 20 patients after renal transplantation. The determinations were made at 4 sites in both radius and tibia. In patients with chronic renal failure on conservative treatment the bone mineral content did not differ significantly from that in normals. Patients on hemodialysis showed a low bone mineral content in 61 percent of females and 53 percent of males. Especially low values were obtained from 5 females who had undergone bilateral nephrectomy. After renal transplantation all female patients showed low values, whereas 50 percent of male patients showed decreased values. No correlations were found between bone mineral content and serum parameters (calcium, phosphate, alkaline phosphatase, creatinine), duration of renal failure, hemodialysis treatment or steroid medication.
In this study of 17 renal transplant recipients with hyperuricemia the effects of allopurinol vs. benzbromarone were compared. Both drugs effectively lowered serum uric acid concentrations by 19 vs. 35% of pretreatment values. Adverse reaction to allopurinol consisted in augmenting of azathioprin toxicity for bone marrow, with occurrence of an isolated fall in the hematocrit in several patients. With benzbromarone no drug interactions were observed. However, one patient exhibited uric acid stone formation in the damaged kidney.
Lipids have been investigated in three groups of patients with chronic renal insufficiency. 19 patients were on conservative treatment (no dialysis), 52 patients were on regular hemodialysis, and 27 patients had been transplanted. The results were compared with those obtained from control subjects of the same age and sex. Hyperlipoproteinemia was found in 25% of the uremic patients, 55% of hemodialysis patients, and 85% of transplant recipients. The predominant lipid abnormalities were hyperlipoproteinemia of Type IV in both uremic (5 out of 19) and hemodialysis patients (17 ou of 52). Hyperlipoproteinemia of Type II was mainly observed after transplantation (IIb: 13, IIa: 5 out of 27).
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