Impact of a sirolimus/tacrolimus-based immunosuppressive regimen on kidney function after islet transplantation.

AIM: Islet transplantation is gaining recognition as a therapeutic option for selected diabetic patients. The immunosuppressive regimen based on sirolimus/low-dose tacrolimus is considered a major breakthrough that allowed considerable improvement in graft survival. A high incidence of side effects associated with such a regimen has been reported in the literature, but this immunosuppressive protocol is generally considered safe or even protective to the kidney. Herein, we analyze the impact of the sirolimus/low-dose tacrolimus-based protocol on kidney function. PATIENTS AND METHODS: Five islet-after-kidney and 5 islet-transplant-alone patients were enrolled and followed up. Renal function was assessed by the periodic measurement of serum creatinine and by the presence of albuminuria. Metabolic control markers and graft function were followed, as well as immunosuppressive whole blood trough levels. RESULTS: Kidney function significantly decreased in 6 of 10 patients. Neither metabolic markers nor immunosuppressive drugs levels were significantly associated with the decreased kidney function. CONCLUSION: Although a specific etiology was not identified, subsets of patients presented a higher risk for decrease of kidney function. The presence of low creatinine clearance, albuminuria, and long-established kidney graft were associated with poorer outcomes.

Retransplantation of discordant xenogeneic islets with costimulatory blockade.

BACKGROUND: The aim of the study was to analyze the possibility of xenogeneic islet retransplantation using costimulatory blockade. METHODS: Streptozotocin-induced diabetic mice were transplanted under the kidney capsule with human islets. Mice were nephrectomized and retransplanted with 1000 human islets under the contralateral kidney capsule 14 days later. Four groups were performed group I, first and second Tx without MR1; group II, first Tx without MR1, second Tx with MR1; group III, first Tx with MR1, second Tx without MR1; group IV, first and second Tx with MR1. A control group was transplanted only once without MR1 with human islets. After second Tx, cross-matches between recipient, serum and human lymphocyte were done for detection of antidonor antibodies. RESULTS: In the control group, mean graft survival was 13 (+/-7) days. In group I, mean graft survival was 5 +/- 3 days. In group II, mean graft survival was 16 +/- 13 days. In group III, mean graft survival was 81 +/- 22 days. In group IV, no rejection were recorded and all graft survived more than 120 days. Pretransplant cross-matches were negative. In groups I and II all cross-matches were positive, while none were positive in group IV. CONCLUSION: Retransplantation of xenogeneic islets was associated with accelerated rejection. After presensitization, MR1 was unable to induce tolerance to a second Tx. MR1 given at the first Tx only allowed prolonged survival of the second Tx, but rejection still occurred. MR1 given at first and second Tx allowed long-term survival of retransplanted xenoislets and prevented occurrence of antidonor antibodies.

Pregnancy induces a modulation of the cAMP phosphodiesterase 4-conformers ratio in human myometrium: consequences for the utero-relaxant effect of PDE4-selective inhibitors.

The inhibitory impacts of RP 73401, a phosphodiesterase type 4 (PDE4) selective inhibitor of the second generation, versus rolipram, the prototypal PDE4 inhibitor, were evaluated and compared on cAMP phosphodiesterase (PDE) activity and contractility of the myometrium in nonpregnant and pregnant women. In enzymatic studies, RP 73401 and rolipram inhibited the cAMP PDE activity with significantly greater maximal efficiency in the myometrium of pregnant compared with nonpregnant women (75 versus 55%; P <.05). Although myometrial PDE4 presented a single class of interaction with RP 73401 [pD(2) (-log [IC(50)]) = -8.2], it exhibited at least two classes of interaction with rolipram (pD(2) = -8.2 and -5.6). In the myometrium of pregnant versus nonpregnant women, rolipram is significantly more efficacious in the concentration range >0.01 to 100 microM (P <.01), whereas no difference was observed for the concentration range <0.01 microM. In contractility studies, RP 73401 was equally effective in relaxing myometrial strips from both nonpregnant and pregnant women (pD(2) = -8.8). Conversely, the ability of rolipram to inhibit contractions of the myometrium in pregnant women was significantly lower (pD(2) = -7.2) compared with that in nonpregnant women (pD(2) = -8.2; P <.01). Concomitantly, in the myometrium of pregnant women, a rise in immunoreactive PDE4B2 signal was detected, whereas the PDE4D3 signal was less intense. These results demonstrate that parallel to an accumulation of PDE4B2 isoform, a modification in the ratio of PDE4 conformers HPDE4 and LPDE4 (conformer that binds rolipram with high and low affinity, respectively) occurs in the myometrium of near-term pregnant women with an increase of LPDE4 functionally implicated in the contractile process. Such modifications provide a strong rationale to propose LPDE4 as potential pharmacologic targets for the design of new tocolytic treatments.

Acquired hemophilia secondary to factor VIII inhibitors after pregnancy.

We report the case of a 26 year-old woman who developed acquired hemophilia secondary to factor VIII inhibitors, two months after a normal pregnancy. The initial hemorrhagic event was a spontaneous deep muscular hematoma mimicking a deep venous thrombosis. This observation was marqued by the apparition of antibodies against porcin factor VIII under treatment by porcin factor VIII. Intravenous immunoglobulin was ineffective, then cyclophosphamide was necessary to control the disease.

[Celioscopic ovariectomy. Retrospective study of 56 ovariectomies]. / Ovariectomie coelioscopique. Série rétrospective de 56 ovariectomies.

OBJECTIVE: To describe a technique of laparoscopic oophorectomy, and evaluate its feasibility, limits and complications. DESIGN: We performed a retrospective study of 34 patients who underwent laparoscopic oophorectomy, from 1 December 1992 to 28 February 1995. SETTING: Centre Hospitalier Intercommunal, Créteil, and Institut Gustave Roussy, Villejuif. SUBJECTS: Mean age was 58 years (range: 42 to 74 years). In post-menopausal patients with ovarian cyst, a systematic oophorectomy was performed (33 patients). Among post-menopausal women, a systematic contro-lateral oophorectomy was done in 77% of cases. Castration was preconized in one woman with previous breast carcinoma. TECHNIC: Removal of the ovary was performed by dessication and division of the utero-ovarian junction and of the mesovarium. RESULTS: Among the 34 women, 32 (94%) had an exclusive laparoscopic procedure, 2 had laparo-conversion. The reasons of laparo-conversion were the presence of adhesions in one case and presumption of ovarian malignancy (Border-line ovarian tumor) in the other case. For the 32 women with laparoscopic treatment, 22 (65%) had bilateral oophorectomy. Per-operative complication rate was 6.2% (an epigastric vessel injury in one case and an hemorrhage during laparoscopic adhesiolysis in an other case). The post-operative time was uneventful. CONCLUSION: This technique of laparoscopic oophorectomy is simple, rapid and has a low rate of per and post-operative complications. In addition, this technique has the advantage to prevent the risk of ureteral injury.