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Biomedical subjects

D Fries

Publications and source records attributed to D Fries.

At least 19 recordsLinked to original sources
PubMed1992

Immunoadsorption of anti-HLA antibodies for highly sensitized patients awaiting renal transplantation.

Fifteen end-stage renal disease patients with high titres of panel reactive (PRA) antibodies were treated with immunoadsorption (IA) on sepharose-bound protein A columns in order to remove anti-HLA antibodies and facilitate transplantation. 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 panel reaction antibodies, and was hampered by high de novo resynthesis of anti-HLA antibodies. Patients whose pre-IA antibody titre was greater than or equal to 1:64 clearly did not benefit from the procedure, but other immunological criteria were not predictive of efficacy. Twelve patients were transplanted on the basis of a negative cross-match with current serum, historical sera being retrospectively tested. Surprisingly, seven patients received a well-matched graft with both pre- and post-IA negative cross-matching. Graft survival was 86% in this group. Conversely, in the group of five transplants which were performed in recipients having a positive historical cross-match with the donor, graft survival was only 40%. One patient died with a functional graft, and two grafts failed due to hyperacute humoral rejection. Humoral rejection in a third patient was successfully treated by a second IA course and administration of polyclonal IgG. We conclude that IA is a safe procedure for managing hyperimmunized transplant candidates. However, its efficacy remains variable, and a better definition of patients who should benefit from IA needs to be found.

Adsorption↗
PubMed1992

[Liddle syndrome (or pseudo-hyperaldosteronism). Long-term development and erythrocyte potassium flow study in 4 cases].

BACKGROUND: Liddle's syndrome (or pseudoprimary aldosteronism) is a rare hereditary disease; only 18 cases have been reported since 1963. Its cause remains unclear, but one of its features is increased cell membrane permeability to ions. PATIENTS AND METHODS: A diagnosis of Liddle's syndrome was made in 4 new cases, all female, two of them sisters (cases n0 3 and 4), at the ages of 2, 12, 5 and 4 years. The first manifestations were dehydratation with hypokalemia at 6 months (case n0 1), hypertension at 2 years (case n0 2), polydipsia with poor weight and height gain at 5 and 4 years of age (cases n0 3 and 4). At diagnosis, all the patients had severe hypertension, metabolic alkalosis, hypokalemia and hyperkaliuria, low plasma renin activity and serum aldosterone levels. Administration of antihypertensive agents was without effect, but the hypertension was reduced when triamterene and low-sodium diet were used. Hypercalciuria was observed in 2 cases and nephrocalcinosis in 2 (case n0 1 had both hypercalciuria and nephrocalcinosis). The 2 oldest patients (n0 3 and 4) developed progressive kidney failure, possibly due to reno-vascular disease secondary to hypertension. Patient n0 3 underwent kidney transplantation 18 years after the first symptoms of the disease. This resulted in the complete disappearance of her hypokalemia and hypertension. The red blood cell membrane permeability to K+ and Cl- was studied in all 4 cases before triamterene treatment. The passive permeability to K+ and (K+/Cl-) cotransport were both elevated. A second study, 3 years (cases n0 2 and 3) and 8 years (cases n0 1 and 4) later, of patients treated with triamterene showed low values for passive K+ permeability and (K+/Cl-)-cotransport. CONCLUSIONS: The 4 new cases of Liddle's syndrome had the classic features of the disease, except for hypercalciuria and nephrocalcinosis in 2 of them. The cell membrane permeability data are difficult to interpret. Hypokalemia and hypertension were immediately corrected after kidney transplantation in one case and remained so for 4 years, suggesting that this disease is tubular in origin.

Aldosterone↗
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↗