Primary therapy with OKT3 for biopsy-proven acute renal allograft rejection

Our patient underwent right anteromesial temporal resection at 17 years of age for intractable complex partial seizures due to hippocampal sclerosis, and then developed juvenile myoclonic epilepsy after a change in medication. Postoperative seizures ceased after a change to valproate monotherapy. Our patient reminds us to remain aware that generalized and focal epilepsy may coexist as an unusual cause for surgical failure. We feel that these patients may still be favorable candidates for epileptic surgery, as long as the focal epileptogenic zone is amenable to resection and the generalized epilepsy appears to be readily controllable.     

Tacrolimus therapy for persistent or recurrent acute rejection after lung transplantation

Purified native F1 antigen from Yersinia pestis was used to assess controlled-release vaccine delivery systems in poly(lactide-co-glycolide) (PLG) microparticles and liposomes. Antigen encapsulated in PLG microparticles induced high serum titres when injected i.p. in mice: mucosal IgA was also detected. Mice immunized with F1 in Alhydrogel or PLGs were protected against subcutaneous challenge with Y. pestis. F1 antigen surface-labelled onto liposome vesicles stimulated high serum titres in Balb/c mice and also induced a mucosal response: F1-labelled liposomes protected mice against challenge with up to 1 x 10(5) organisms. These findings indicate that a significant immune response is induced by immunizing with F1 formulated in PLGs and liposomes and that protection was achieved after only one dose.     

Prophylaxis of acute renal allograft rejection using FTY720 in combination with subtherapeutic doses of cyclosporine

BACKGROUND: In rodent transplant models, FTY720 exerts a synergistic affect with cyclosporine (CsA) to prolong allograft survival. The present experiments sought to test this combination in subhuman primates. METHODS: Cynomolgus monkeys were transplanted with kidney allografts that were incompatible in mixed lymphocyte culture reactions. The animals were treated with daily intramuscular injections of CsA using doses selected to maintain whole blood trough concentrations at therapeutic values between 40 and 200 ng/ml. The 4 experimental groups included CsA without or with 0.1, 0.3, or 1 mg/kg/day FTY720 delivered daily by intravenous bolus injection. Therapeutic effects were suggested both by the graft histology of biopsy within the first 10 posttransplant days and by the length of host survival. RESULTS: Whereas recipients treated with CsA alone rejected kidney allografts at a median survival time of 8.5 days (n=4), those treated with either 0.1 or 0.3 mg/kg/day FTY720 in addition to CsA showed significant prolongation of kidney allograft survival to 71 days (n=3; P<0.04) or 63 days (n=5; P<0.05), respectively. The hosts in the 1.0 mg/kg/day FTY720 group survived 48 days, with 2 of 5 recipients succumbing at 9 or 17 days postgraft, suggesting possible complications caused by overimmunosuppression. Biopsies of the 0.1 mg/kg/day FTY720 group on posttransplant day 7 documented mild to moderate rejection (grade I), indicated by multiple focal areas of tubular destruction. The histology results of transplants in the 0.3 or 1 mg/kg/day FTY720 group showed only minimal interstitial inflammatory infiltrates (borderline grade), with no evidence of tubular or arterial damage. Serum creatinine values among the animals in the 0.1 mg/kg/day FTY720 group showed increases in 2 of 3 recipients by day 20 and in the third by day 41 postgraft. Among the 0.3 mg/kg/day FTY720 group, 3 of 5 recipients maintained baseline creatinine values to 45 days postgraft; 1 recipient had stable kidney function for 120 days postgraft. CONCLUSIONS: Addition of FTY720 therapy to a subtherapeutic CsA immunosuppressive regimen delays the rejection of renal allografts in subhuman primates.     

Percutaneous renal biopsy in children: a 27-year experience

BACKGROUND: The introduction of automated biopsy devices and the localization of the kidney by ultrasound were aimed at optimizing efficacy and safety of the percutaneous renal biopsy procedure. We evaluated these technological advances in our renal biopsies performed in children. METHODS: We sequentially used the Silverman needle (1969-1974), the TruCut needle (1974-1990), and the automated Biopty device (1990-1996). Fluoroscopy was used to localize the kidney until 1985, ultrasound examination prior to biopsy from 1985 to 1992, and direct ultrasound guidance since 1992. A total of 962 native kidney biopsies and 119 allograft biopsies were performed. RESULTS: In the native kidney biopsies, the introduction of the Biopty device and ultrasound guidance were independently associated with fewer passes required to obtain adequate tissue and more glomeruli per specimen. The rate of biopsies yielding more than 9 glomeruli increased from 69 to 92% (p < 0.05). The number of glomeruli harvested per centimeter core length was inversely related to patient age (p < 0.01). More appropriate cortical tissue was retrieved in renal allograft biopsy specimens with the application of the new techniques. The occurrence of macroscopic hematuria (9. 6%) in the native kidney biopsies was not affected by the puncture or localization technique applied, but subcapsular hematomas were documented more often with the Biopty device (42%) than with the TruCut needle (16%), probably due to improved ultrasound equipment. In the whole series 2 patients died, and 3 others required renal surgery and 4 blood transfusions. CONCLUSIONS: The automated ultrasound-guided procedure is a feasible and reliable technique for percutaneous renal biopsy in children. It gives a greater yield of diagnostic tissue without increasing the rate of clinical complications.     

Successful induction and consolidation therapy of acute myeloid leukaemia in a renal allograft recipient

Immunosuppressed organ transplant recipients have a markedly increased risk of neoplasia. Among these malignancies acute myeloid leukaemia (AML) is rare. However, until now no case of successful chemotherapy has been reported. We present a 39-year-old male patient who developed AML (FAB M4 Eo) 4 years after renal transplantation and achieved a stable complete remission after induction therapy with standard dose cytarabine and daunorubicin. Remission duration is now 11 months. At present the transplant is functioning well after two additional courses of consolidation chemotherapy with high-dose cytarabine combined with mitoxantrone and idarubicine respectively. Cyclosporin A was given during all cycles of chemotherapy. We conclude that intensive chemotherapy in patients with AML following renal transplantation in good performance status is feasible.     

Post transplant diabetes mellitus in live related renal allograft recipients: a single centre experience

The incidence of post-transplant diabetes mellitus (PTDM) was evaluated in 250 patients who underwent live-related renal transplantation at our hospital between 1978 and 1992. Twelve (4.8%) patients developed PTDM requiring drug therapy. PTDM occurred in 4 of 197 (2%) patients on conventional prednisolone-azathioprine immunosuppression as compared to 8 of 53 (15.1%) patients receiving cyclosporine in addition (triple-therapy). Three patients (25%) developed PTDM during or immediately following anti-rejection therapy with intravenous methylprednisolone. Eight patients (66.6%) developed PTDM within six months of transplantation. Majority of our patients (66.6%) could be managed successfully with oral hypoglycemic agents. Two patients (16.6%) showed spontaneous resolution of hyperglycemia within six months of onset of PTDM. Eleven patients (91.6%) were symptomatic for their hyperglycemia with two patients presenting as 'pseudorejection' and one with diabetic ketoacidosis. Females were more predisposed to develop PTDM in our study (10% vs. 4.1%). HLA-B15 and DR 3 were the commonest phenotypes in our PTDM patients. No other known predisposing or triggering factors associated with PTDM were found in our patients. The current study suggests, that addition of cyclosporine to the conventional immunosuppression in live-related renal allograft recipients has contributed to an increased incidence of post-transplant diabetes mellitus. Close and regular blood sugar monitoring is thus recommended in post-transplant patients especially those on triple drug immunosuppression.     

Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group

BACKGROUND: Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30% to 50% of these patients. In the phase III study described here we assessed the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal antibody, to prevent acute-rejection episodes in renal allograft recipients. METHODS: 380 adult recipients of a primary cadaveric kidney transplant were randomly allocated, in this double-blind trial, to receive a 20 mg infusion of basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study. The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation. Safety and tolerability were monitored over the 12 months of the study. FINDINGS: 376 patients were eligible for intention-to-treat analysis (basiliximab, n=190; placebo, n=186). No significant differences in patient characteristics were apparent. The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73 (44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan-Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At weeks 2 and 4 post-transplantation, the mean daily dose of steroids was significantly higher in the placebo group (p<0.001 with one-way analysis of variance). The incidence of graft loss at 12 months post-transplantation was 23 (12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and other adverse events was similar in the two treatment groups. The acute tolerability of basiliximab was excellent, with no evidence of cytokine-release syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%], p=0.293) occurred during the 12-month study and a further three deaths (basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One post-transplantation lymphoproliferative disorder was recorded in each group. INTERPRETATION: Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly, with no clinically relevant safety or tolerability concerns.     

The treatment of acute traumatic rupture of the aorta: a 10-year experience

Forty-three patients with aortic rupture secondardy to blunt trauma have been treated at the University of Micigan within the past 10 years with an overall salvage rate of 70%. The diagnosis should be suspected in anyone who has sustained a high speed decelerating injury, if the chest roentgenogram shows media-stinal widening, whether or not there is hypertension of the upper extremities; systolic murmur, or external evidence of chest injury. Aortography should be employed to confirm the diagnosis and to determine the site or sites of rupture. Repair of the lesion should be undertaken as soon as possible and takes priority in most instances over associated injuries. Repair in almost all cases can be accomplished safely and quickly using a bypass shunt without the aid of extracorporeal circulation.     

Diagnosis and therapy of aortic prosthetic fistulas: trends over a 30-year experience

A retrospective study was carried out of patients from a single institution over a 30-year period. Thirty-one patients presented with 33 fistulas, four non-enteric and 27 enteric. In 25 of 27 patients with a prosthesis-related enteric fistula gastrointestinal bleeding was present. Angiography revealed the fistula in five patients endoscopy in three, and barium studies, echography and computed tomography each revealed one fistula. Six patients died before and five died during operation. In 20 patients various techniques were used for treatment. In-hospital mortality decreased from six of eight patients before 1970, to seven of ten between 1971 and 1980, and to four of 13 after 1981. In the long term, patients treated with an extra-anatomic reconstruction had a poorer prognosis than those treated by in situ reconstruction. This experience shows that diagnostic tests often fail to reveal a prosthesis-related fistula and that mortality can be substantially reduced by early exploration in patients with negative diagnostic studies.