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Biomedical subjects

D Fries

Publications and source records attributed to D Fries.

At least 37 records · Page 2Linked to original sources
PubMed1992

How to deal with the hyperimmunized potential recipients.

End-stage renal disease (ESRD) patients with high levels of anti-HLA panel reactive antibodies (PRA) represent an increasing group in which sensitization, induced by pregnancies, previous transplants, and blood transfusions, considerably delay the opportunity to receive a graft. Currently, more than 50% of the 4700 patients awaiting transplantation in France are sensitized, of which 33% are defined as hyperimmunized (PRA greater than = 80%), and only 9.5% of the total number of transplants have been done in highly sensitized recipients. The magnitude of this problem, similar in Europe and North America, explains why more active strategies for managing hyperimmunized patients have been introduced during the past decade. Clearly, the simplest is finding of a well-matched organ that does not carry the HLA antigens against which the recipient has generated antibody, but that is limited by the number of shared grafts. The second is the development of a new cross-matching technique prior to transplantation. Attempts at immunoregulation of secreting B cell clones have been carried out using either hypertransfusions or injection of polyclonal Ig. Finally, removal and prevention of the resynthesis of HLA antibodies is a most attractive approach using immunoadsorption (IA) system with sepharose-bound protein-A columns. In our unit, fifteen ESRD patients with high levels of PRA were treated with IA. Infectious complications were not observed after IA and transplantation, and the procedure was well tolerated. In spite of the use of adjunctive immunosuppressive treatment with cyclophosphamide and prednisolone, this method produced only variable effects in lowering PRA levels, and was hampered by high de novo resynthesis of anti-HLA antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1991

[Treatment of cytomegalovirus infections with ganciclovir in kidney transplant recipients. Clinical and pharmacokinetic study].

Ganciclovir (DHPG) was used in 32 renal transplant recipients with proven cytomegalovirus (CMV) disease. Mean time of CMV occurrence from grafting was 49 days. CMV disease was recognized on the combination of both clinical signs and histological or virological findings. DHPG treatment, adapted to renal function was given for 14 days and a pharmacokinetic study was performed at days 1, 7 and 14. Twenty nine patients, 10 of whom has severe to moderate disease, were improved by treatment. Three patients died, 2 of them with severe pulmonary and hepatic diseases. Few adverse effects were observed (leucopenia: n = 7, thrombopenia: n = 2, abdominal pain: n = 1). CMV was no longer found in virological samples in 80 percent of the patients. Maximal plasma concentration of DHPG (9.3 +/- 0.3 micrograms/ml, m +/- SEM) was reached at the end of the one hour infusion and decreased according to a biexponential model. The half life of elimination was 3.35 +/- 0.32 hours, the metabolic clearance 128 +/- 7 ml/min and the distribution volume about 50 percent body weight (0.48 +/- 0.02 l/kg). The clearance of DHPG was greater than creatinine clearance, and was linearly correlated with it, suggesting that renal elimination was important, both by glomerular filtration and tubular secretion. These results indicate that DHPG is effective and well tolerated for the treatment of CMV disease in renal transplant recipients. Renal elimination of the drug requires dosage adjustment to renal function.

Adult↗
PubMed1991

[Acute clinical syndrome associated with OKT3 administration. Prevention by single injection of an anti-human TNF monoclonal antibody].

This study analyzed the capacity of an anti-human tumour necrosis factor (TNF) monoclonal antibody, CB006 (murine IgG1, Celltech), to prevent the OKT3-induced acute clinical syndrome. Fourteen renal allograft recipients undergoing prophylactic OKT3 therapy were included. CB006 was administered as a single i.v. injection, 0.4 mg/kg (Group I, 7 patients) and 2 mg/kg (Group II, 7 patients), one hour prior to the first OKT3 administration. Nineteen consecutive patients that were part of a randomized multicenter trial constituted the historical control group. In all patients CB006 was perfectly well tolerated and significantly decreased the frequency of the common OKT3-associated acute symptoms. None of the CB006 pretreated patients showed severe life threatening symptoms (hypotension, respiratory distress or neurotoxicity), observed in 10 per cent of historical controls. At variance with controls, in CB006 treated patients gastrointestinal symptoms (vomiting, diarrhea) and pyrexia (body temperature greater than or equal to 39 degrees C) appeared in low frequency, were mild and short lasting, never promoting major prostration of the patients due to electrolytes and fluid loss. Importantly, the presence in some patients of these mild symptoms, correlated with detectable bioactive TNF in the circulation thus reflecting incomplete blockade by CB006 of OKT3-induced TNF. CB006 pharmacokinetics data further stressed the need for adequate dosage adaptation. CB006 did not affect the biological or clinical effectiveness of OKT3. None of the patients showed evidence of anti-CB006 xeno-sensitization.

Antibodies, Monoclonal↗
PubMed1991

[Treatment with Lo-Tact-1, a monoclonal antibody to the interleukin-2 receptor, in kidney transplantation].

From May to August 1989 15 cadaver-donor renal transplant recipients were treated for 14 days with LO-Tact-1 (10 mg i.v. per day) in combination with cyclosporin (8 mg/kg/day from day-1), low-dose steroids (1/2 mg/kg/day from day 1, then reduced to 0.25 mg/kg at day 26 and 10 mg/day at day 45), and azathioprine (1 mg/kg/day) started at day 45. LO-Tact-1 is a rat monoclonal antibody which is directed to the interleukin-2 receptor. The control group consisted of 20 patients receiving cyclosporin, high-dose steroids (2 mg/day at day 1) and a 14-day course of polyclonal horse antilymphocyte globulins (ALG). Seven patients experienced 9 rejections during the first 3 months post-transplant between day 10 and day 67 (mean 0.6 per patient), comparable to the incidence of rejections in the control group: 8 rejections in 7 patients (mean 0.4 per patient). All rejections were reversed by steroid boluses and ATG. To date, all study patients have functioning grafts, and at 1-year post-transplant, the mean blood creatinine level is 161.2 mumol/l. In the control group, one patient died of CMV infection, and 2 other grafts failed due to rejection. No adverse effect of antibody administration was observed, and hematological changes remained of minor importance. Viral infections were not observed, except one case of herpes simplex. Comparatively, clinical CMV infections occurred in 3 patients receiving ALG (15 percent). Our data suggest that a combination anti-IL-2 monoclonal antibody, cyclosporin and low-dose steroids can safely be administered to allograft recipients, avoid severe viral infections, and, in our early experience, is as potent as the powerful combination ALG, cyclosporin and high-doses steroids in preventing allograft rejection.

Adult↗
PubMed1991

[Arterial stenosis in the renal graft. Indication for endoluminal dilatation].

One hundred and thirty eight patients with renal transplant artery stenosis were reported in a series of 1200 renal transplants. These cases included 47 patients in whom hypertension was well controlled by means of hypotensive drugs, 39 patients treated by surgical repair (SR) and 49 treated by percutaneous angioplasty (PTA). The long-term success rate was 81.5 percent in the SR group compared with 40.8 percent in the PTA group. PTA morbidity was greater than that of SR, and we believe that after the initial optimism, the results of this technique should be reevaluated according to the anatomical pattern of the renal artery stenosis.

Adolescent↗
PubMed1991

[Arterial stenosis in the renal graft. Spontaneous evolution in 40 cases].

From January 1976 to June 1989, 138 renal artery stenoses (RAS) occurred in a population of 1,200 renal transplantations in a single center (11.5 percent). An interventional procedure was performed in 89 patients: surgery in 39 and transluminal angioplasty in 50. Six other patients were excluded from the study because of complications and RAS spontaneously disappeared in 3 patients. Finally, 40 patients were treated medically with a mean follow-up of 57.6 months (range 12 to 116 months). In this group, the actuarial graft survival rate did not significantly differ from that of the 2 other groups. One patient only lost his graft from renal artery thrombosis. The mean serum creatinine level at the time of RAS diagnosis (140 +/- 8.6 mumol/l) was not significantly different from the mean serum creatinine level at the last follow-up (146 +/- 14.6 mumol/l). The degree of hypertension, graded on the number of anti-hypertensive drugs, was not different at the time of diagnosis and at the end of follow-up. In conclusion, in our experience, the spontaneous course of RAS does not result in an increased rate of graft failure or impaired long-term renal function.

Adult↗
PubMed1991

EBV cell-lines (LCL) and E- cells as stimulator cells for limiting dilution analysis (LDA) of alloreactive IL-2-secreting cells (IL-2-SC) and cytotoxic precursors (CTLp). Comparison of their stimulator capacity and ability to generate specific alloreactivity.

The choice of stimulator cells is crucial in determining the frequency of alloreactive cells by limiting dilution analysis (LDA). In humans, E- cells or EBV-lymphoblastoid cell lines (LCL) are available for this purpose. The E- cells have been mostly used until now, but they appear to stimulate much less than LCL in other models. Consequently, we undertook a systematic comparison of the efficiency of both types of cell for the LDA of alloreactive IL-2-secreting cells (IL-2-SC) and cytotoxic precursors (CTLp). We show that LCL are stronger stimulator cells both for IL-2 secretion and for cytotoxicity induction. However, high levels of non-allogeneic reactivity were also induced. Therefore, to measure the frequency of specific alloreactive IL-2-SC and CTLp, T cells were depleted of such irrelevant reactive cells by a suicide technique: culture with autologous LCL in the presence of BUDR and use of the remaining live cells as responding effectors in LDA. Using this methodology, no non-allogeneic reactive T cells remain in the responding cells: after restimulation by autologous LCL, no IL-2-SC could be seen and no cytotoxic activity could be observed against autologous, irrelevant or LAK sensitive targets. In contrast, the number of IL-2-SC and CTLp against allogeneic targets was preserved. Therefore with this methodology, the strong stimulator capacity of LCL could be used whereas non-specific activation could be avoided in order to assess the frequency of allo-specific IL-2-SC and CTLp.

Bromodeoxyuridine↗
PubMed1991

Decrease in renal vascular resistance in University of Wisconsin solution preserved kidney transplants.

Renal vascular resistance was compared in 2 groups of renal grafts: group 1-16 kidneys perfused with University of Wisconsin solution and group 2-16 kidneys perfused with Euro-Collins solution. Both groups had comparable donors and recipient criteria. Renal blood flow was measured by a miniaturized pulsed Doppler probe fixed on the graft renal artery. Renal vascular resistance was calculated either according to the formula: renal vascular resistance (mm. Hg/ml. per second) = systemic arterial pressure (P)/renal blood flow or through the renal vascular resistive index (RVRI): RVRI = systolic flow velocity - diastolic flow velocity/systolic flow velocity = (S-D)/S. Renal vascular resistance estimation seems to be more contributory than renal blood flow in assessment of renal graft reperfusion disorders. Our results show that University of Wisconsin solution seems to preserve intrarenal arterial caliber better with a decrease in intrarenal vascular resistance, thus, allowing for a higher arterial graft perfusion flow.

Adenosine↗
PubMed1991

Acute renal thrombosis induced by angiotensin-converting enzyme inhibitors in patients with renovascular hypertension.

Acute reversible renal failure is a widely recognized potential complication of angiotensin-converting enzyme inhibitor (ACEI) administration in renovascular hypertension, particularly in bilateral artery stenosis or stenosis involving a solitary kidney. We report herein 2 cases of a rare but severe complication, i.e., acute renal artery thrombosis. Whereas marked hypotension does not seem to be necessary to trigger acute renal failure following ACE inhibition, by contrast, the fall in blood pressure could play an important role in our patients. Since single-dose ACEI has been advocated in order to improve the predictive value of renal scintigraphy or plasma renin activity measurements in the diagnosis of renovascular hypertension, the potential risk of this approach should be stressed.

Acute Disease↗
PubMed1990

Persistence of donor-specific IL-2-secreting cells and cytotoxic T lymphocyte precursors in human kidney transplant recipients evidenced by limiting dilution analysis.

The low reactivity to donor alloantigens reported in PBL from kidney transplant recipients might be related to clonal deletion and/or suppression of donor-specific alloreactive cells. To discriminate between these two hypotheses, we quantified the number of IL-2 secreting cells (IL-2-SC) and of cytotoxic precursors (CTLp) in the T cells from tolerant recipients when stimulated with either donor specific or nonrelated third-party LCL. To eliminate the irrelevant reactivity, we used as responding cells high-density T cells that had been depleted of such reactivity by 4 days preculture with autologous lymphoblastoid cell line in the presence of bromodeoxyuridine. Thus, frequencies of IL-2-SC and CTLp specifically directed at alloantigens could be measured. In 11 recipients, there was no strong decrease in the frequency of donor-reactive T cells when compared to the frequency of those directed at a third-party lymphoblastoid cell line, either for IL-2-SC (tested in 11 patients) or for CTLp (tested in 6 patients). In three cases of seven, a suppression was observed only when T cells were stimulated by donor cells. These data suggest that donor-reactive cells are still present in PBL of kidney-transplant recipients tested from 6 mo to 4 y posttransplantation. Moreover, suppression of donor-specific cells can be demonstrated in peripheral T cells of some recipients, which may account in part for the absence of rejection.

Histocompatibility↗
PubMed1990

Transplant renal artery stenosis: experience and comparative results between surgery and angioplasty.

One hundred thirty-eight patients with transplant renal artery stenosis (TRAS) were identified among 1200 patients undergoing renal transplantation in our university hospital. Severe systemic hypertension was the main symptom leading to a diagnosis of TRAS. Only 88 TRAS patients were given interventional treatment consisting of percutaneous angioplasty (PTA; n = 49) or surgical repair (SR; n = 39). The immediate success rate was 92.1% for SR and 69% for PTA. The long-term success rate was 81.5% for SR and 40.8% for PTA, with a follow-up period of 56.7 +/- 22.4 months (SR group) and 32 +/- 28.1 months (PTA group). PTA morbidity reached 28%, compared to 7.6% in the SR group. In spite of these results, we still favor PTA as a first line interventional treatment when TRAS is recent, linear, and distal and primary SR in cases of kinking and proximal TRAS.

Adolescent↗
PubMed1990

Decreased lymphokine-activated killer cells in kidney transplant recipients. Correlation with a diminished number of CD3-/NKH1+ cells.

The activity of lymphokine-activated killer cells, measured either by a clonal or polyclonal technique, was assessed in 30 kidney transplant recipients (TX), in 13 hemodialyzed patients (HD-CRI), and in 18 normal (N) controls. A highly significant decrease of the LAK activity in TX in comparison with HD-CRI or N (P = 0.0001) was observed. Moreover, the percentage of CD3-/NKH1+ cells was decreased in TX in comparison with N (P = 0.01). LAK activity was strongly correlated (r = 0.72; P = 0.0001) with the percentage of CD3-/NKH1+ cells and not with that of double-positive CD3+/NKH1+ cells. Multivariate analysis showed that the sole independent variable that determined the LAK activity was the percentage of CD3-/NKH1+ cells: the pathological status (TX, HD-CRI, and N) variable was statistically not significant. On the other hand, two T cell-specific functions (IL-2 secretion and specific cytotoxic activity) were, on the whole, preserved in TX. Altogether, these results suggest that TX are LAK deficient predominantly because they have a decreased number of CD3-/NKH1+ cells. The normality of T cell functions suggests that the high rate of malignancies seen in TX is related to this LAK deficiency. Moreover, our study indicates that, in vivo, CD3+ cells do not significantly contribute to the LAK precursors.

Antigens, CD↗