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J M Dubernard

Publications and source records attributed to J M Dubernard.

At least 55 records · Page 3Linked to original sources

Antibody-induced modulation of the leukocyte CD11b integrin prevents mild but not major renal ischaemic injury.

BACKGROUND: CD11/CD18 beta(2) integrins are involved in leukocyte adhesion to the activated endothelium, and therefore represent a possible therapeutic target in the prevention of ischaemic acute renal failure (ARF). METHODS: To assess the effect of an anti-CD11b monoclonal antibody (mAb) in ischaemic ARF, uninephrectomized Fischer rats were subjected to 45 or 60 min of warm renal ischaemia, then received 1 mg of anti-CD11b mAb 5 min before reperfusion. RESULTS: After 45 min of ischaemia, renal function tests at 24 and 48 h were less altered in mAb-treated than in control rats, but after 60 min of ischaemia the same level of renal insufficiency was observed in the two groups. In parallel, milder tubular necrosis and less leukocyte infiltration were observed in the treated group after 45 min of ischaemia, but no difference was seen after 60 min compared to the control group. The mAb was detected on blood neutrophils up to 48 h after infusion and a marked down-regulation of CD11b expression on neutrophil surfaces was documented by flow cytometry. CONCLUSION: These results indicate that anti-CD11b mAb administered prior to reperfusion decreases moderate ischaemic ARF but fails to prevent renal injury secondary to prolonged ischaemia in this model.

Animals↗

Evidence of recurrent type I diabetes following HLA-mismatched pancreas transplantation.

Type 1 diabetes mellitus is considered as an autoimmune disease against beta cells. Diabetes recurrence after pancreas transplantation is well known in HLA-identical twins while it is rarely reported in recipients of cadaveric pancreatic grafts. In the present case report, diabetes recurrence occurred in a recipient who underwent cadaveric combined pancreas kidney transplantation. Seven years after transplantation the patient exhibited progressive hyperglycemia needing insulin therapy while the renal graft was well functioning. The diagnosis of recurrent disease was obtained on the histological features such as selective loss of beta cells without clear signs of insulitis and on the presence of markers (GAD 65 and IA-2) for humoral autoimmunity. It is intriguing that, at the time of recurrence of type 1 diabetes, the patient had stopped steroids and azathioprine, while only cyclosporine was maintained as immunosuppressive treatment. Our case report underlines the relevance of studying the humoral autoimmune response directed to islet autoantigens in cadaveric pancreas allograft recipients. Furthermore, it suggests that an efficient immunosuppressive treatment after transplantation may be able to reduce the autoimmune response against the pancreatic allograft.

Adolescent↗

Human hand allograft: report on first 6 months.

BACKGROUND: Long-term survival of animal limb allografts with new immunosuppressant combinations and encouraging results of autologous limb replantations led us to believe that clinical application of hand transplantation in human beings was viable. METHODS: On Sept 23, 1998, we transplanted the right distal forearm and hand of a brain-dead man aged 41 years on to a man aged 48 years who had had traumatic amputation of the distal third of his right forearm. The donor's arm was irrigated with UW organ preservation solution at 4 degrees C, amputated 5 cm above the elbow, and transported in a cool container. We dissected the donor limb and the recipient's arm simultaneously to identify anatomical structures. Appropriate lengths of viable structures were matched. Transplantation involved bone fixation, arterial and venous anastomoses (ischaemic time 12.5 h), nerve sutures, joining of muscles and tendons, and skin closure. Immunosuppression included antithymocyte globulins, tacrolimus, mycophenolic acid, and prednisone. Maintenance therapy included tacrolimus, mycophenolic acid, and prednisone. Follow-up included routine post-transplant laboratory tests, skin biopsies, intensive physiotherapy, and psychological support. FINDINGS: The initial postoperative course was uneventful. No surgical complications were seen. Immunosuppression was well tolerated. Mild clinical and histological signs of cutaneous rejection were seen at weeks 8-9 after surgery. These signs disappeared after prednisone dose was increased (from 20 mg/day to 40 mg/day) and topical application of immunosuppressive creams (tacrolimus, clobetasol). Intensive physiotherapy led to satisfactory progress of motor function. Sensory progress (Tinel's sign) was excellent and reached the wrist crease (20 cm) on day 100 for the median and ulnar nerves, and at least 24 cm to the palm by 6 months when deep pressure, but not light touch sensation, could be felt at the mid palm. INTERPRETATION: Hand allotransplantation is technically feasible. Currently available immunosuppression seems to prevent acute rejection. If no further episode of rejection occurs, the functional prognosis of this graft should be similar to if not better than that reported in large series of autoreconstruction.

Adenosine↗

In vivo effects of monoclonal antibodies against rat beta(2) integrins on kidney ischemia-reperfusion injury.

BACKGROUND: Ischemia-reperfusion (IR) involves adhesion of leukocytes to the activated endothelium, leading to tissue damage. CD11/CD18 beta(2) integrins interact with their ligands on endothelial cells and may therefore represent a therapeutic target for the prevention of IR. We investigated the effects of three monoclonal antibodies (mAbs) that recognize epitopes of heavy or light chain of the beta(2) integrins on IR in kidneys. METHODS: Uninephrectomized Fischer rats were subjected to 45 or 60 min of renal ischemia, treated with intravenously anti-beta(2) integrin monoclonal antibodies (anti-CD11a, anti-CD11b, and anti-CD18) 5 min prior to reperfusion, and compared to a nontreated group. Serum creatinine, blood urea nitrogen (BUN), and kidney histopathological damages were assessed at 1, 2, and 7 days after ischemia. RESULTS: After 45 and 60 min of ischemia, serum creatinine and BUN were significantly higher in the control than in animals treated with anti-CD11a and anti-CD18 at 24 and 48 h. Administration of anti-CD11b had a beneficial effect on renal function after 45 min but not after 60 min of ischemia. Histologic and immunostaining studies demonstrated mild tubular necrosis and less leukocyte infiltration in the anti-CD11a- and anti-CD18-treated groups compared to the control group. CONCLUSION: These results indicate that selected antibodies to CD11a/CD18 may decrease kidney IR injury when administered prior to reperfusion.

Animals↗

[The first transplantation of a hand in humans. Early results].

The first hand allograft was performed on September 23, 1998. The right distal forearm and hand of a brain dead donor was transplanted to a 48 year old recipient who had undergone a traumatic amputation of the distal third of his right forearm. The donor's arm was irrigated with organ preservation solution (UW) and transported to Lyon in a cool container. Two teams simultaneously dissected the donor's limb and the recipient's stump to identify anatomical structures. Transplantation involved bone fixation, arterial and venous anastomoses, nerve sutures, joining of the muscles and tendons, and skin closure. Immunosuppression consisted of anti-lymphocyte, polyclonal and monoclonal antibodies, tacrolimus, mycophenolic acid, and prednisone. Mild clinical and histological signs of rejection occurred at week 9 after surgery. They disappeared with adjustments of the immunosuppressant doses. Seven months after surgery the patient was in good general condition. Intensive physiotherapy led to satisfactory progress of motor function. Sensory progress is excellent, reaching the fingertips. A longer follow-up is necessary to appreciate the final result. In the absence of further rejection, the functional prognosis of the graft should be similar to that reported after successful autoreconstruction.

Adenosine↗

Effect of the surgical technique on long-term outcome of pancreas transplantation.

To date there is no general consensus as to the best surgical technique for pancreas transplantation. Patients with a pancreas transplant functioning for 3 years or more were retrospectively investigated to compare three surgical techniques: segmental graft with duct obstruction (DO), whole graft with bladder drainage (BD), and whole graft with enteric drainage (ED). Several parameters were studied: patient and graft survival, rejection, long-term surgical and medical complications, and endocrine function. The best results in terms of graft survival and quality of metabolic control were obtained in the group that underwent whole graft transplantation with ED. At 3 years, overall pancreas graft survival was 65% for ED, 60% for BD, and 47% for DO. This surgical method has become the preferred technique in our unit.

Adult↗

[Preliminary results of the treatment of 44 patients with localized cancer of the prostate using transrectal focused ultrasound].

OBJECTIVE: To evaluate the efficacy and morbidity of treatment of localized prostatic cancer using transrectal high-intensity focused ultrasound. MATERIAL AND METHODS: 44 patients (mean age: 72 years) with clinical stage T1 (20) or T2 (24) prostatic cancer, not eligible for radical prostatectomy, were treated by two different prototypes of the Ablatherm (Technomed Medical System). The second prototype includes several safety devices designed to reduce morbidity. 99 sessions were performed, i.e. an average of 2.25 sessions per patient: the prostate was treated in one session (5 patients), 2 sessions (26 patients), 3 sessions (10 patients), or 4 sessions (3 patients), usually under spinal anaesthesia. The mean PSA was 9.92 ng/ml and the mean prostatic weight was 37 g. RESULTS: Complications occurred in 10 (50%) of the first 20 patients treated (1993-1995): 2 recto-urethral fistulas, 2 asymptomatic rectal burns, 2 cases of stable urinary retention, 1 case of severe incontinence, 3 cases of bladder neck sclerosis, and 1 febrile urinary tract infection. In the 24 patients treated subsequently (1995-1997), complications occurred in only 4 patients (16%): 1 case of stable urinary retention, 1 febrile urinary tract infection, 1 case of bladder neck sclerosis, 1 case of stress incontinence. A complete response (repeated negative follow-up biopsies) was obtained in 27 patients (61%). The mean post-treatment PSA level in patients of this group was 1.09 +/- 1.06 and remained stable (mean follow-up: 346 days; range: 60-1250). A residual cancer was detected in 17 patients (39%). 8 patients were considered to be failures (mean post-treatment PSA: 4.8 ng/ml) and received adjuvant treatment (hormonal: 3; external radiotherapy: 5). Complementary treatment by focused ultrasound will be performed in another 9 patients, if their PSA rises above 3 ng/ml (patients of this group are symptomatic with a mean post-treatment PSA of 1.6 ng/ml). CONCLUSION: The morbidity of treatment by transrectal focused ultrasound has now been reduced. These results suggest that this new treatment can constitute a useful option for certain patients with localized cancer, not suitable for radical prostatectomy.

Adenocarcinoma↗

[Hazards of lumbar ureteroscopy: apropos of 4 cases of avulsion of the ureter].

Ureteroscopy is frequently indicated in the treatment of stones of the pelvic ureter. Access to the lumbar ureter is associated with a higher complication rate: wounds, ureteric rupture, haemorrhage, or more serious lesions such as avulsions of the ureter. We present 4 cases of avulsion of the ureter seen in our department, corresponding to 4 men with stones of the lumbar ureter treated by ureteroscopy, 2 of them after failure of in situ extracorporeal lithotripsy (ESWL) and an attempt to "flush" the stone and the other two because ESWL was not available. The ureteric lesion was related to a Dormia catheter in 2 cases and the ureteroscope in 2 cases. The lesion was diagnosed and treated immediately in 2 patients and after a delay in the other 2 cases. Repair consisted of ureteric reimplantation on a Boari flap (1 case), implantation onto a psoas bladder (1 case), ureteroileoplasty (1 case) and autologous transplantation (1 case). Ureteric lesions prevented uretero-ureterostomy. Ureteric reimplantation on psoas bladder and/or Boari flap appears to be the simplest method, but it cannot always be performed. In the case of avulsion of the ureteropelvic junction with a large defect, autologous transplantation is a method of choice in young subjects. Ureteroileoplasty appears to be reserved for elderly patients.

Adult↗

Pancreas transplantation: results and indications.

Pancreatic transplantation is the best method of replacing the endocrine function of the gland in Type 1 insulin-dependent diabetic patients. At the end of 1996, 9,000 pancreas transplants had been reported to the international Pancreas Transplant Registry. For 1994-1996, one-year pancreas survival rates were 81% for simultaneous pancreas and kidney transplantation (n = 1,516), 71% for pancreas after kidney (n = 141) and 64% for pancreas alone (n = 64). In patients with a functional graft, glycosylated haemoglobin, fasting blood sugar, and 24-h metabolic profiles are normal. The effect of pancreatic transplantation on secondary complications often appears after several years of normal pancreatic function. Successful transplantation is associated with an improvement in different aspects of the quality of life. The decision to perform pancreatic transplantation depends on the balance between the risks of transplantation, mainly surgical or related to immunosuppression, and those of diabetes development. The advantages and drawbacks of pancreatic transplantation and insulin therapy need to be honestly and carefully analysed for specific populations of diabetic patients as well as for each individual. At present, simultaneous pancreaticorenal transplantation is the best treatment for diabetic patients with chronic renal failure. Transplantation of the pancreas alone in non-uraemic patients may also be considered in carefully selected subjects.

Diabetes Mellitus, Type 1↗