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J P Squifflet

Publications and source records attributed to J P Squifflet.

At least 19 recordsLinked to original sources
PubMed2002

Adult porcine islet transplantation in baboons treated with conventional immunosuppression or a non-myeloablative regimen and CD154 blockade.

The aim of the present study was to assess the survival of adult porcine islets transplanted into baboons receiving either (I) conventional triple drug immunosuppressive therapy or (2) a non-myeloablative regimen and an anti-CD154 monoclonal antibody (mAb) aimed at tolerance-induction. Group 1 baboons (n = 3) were pancreatectomized prior to intraportal injection of 10,000 porcine islet equivalents (IE)/kg and immunosuppressed with anti-thymocyte globulin (ATG), cyclosporine and azathioprine. In Group 2 (n = 2), non-pancreatectomized baboons underwent induction therapy with whole body and thymic irradiation, and ATG. Extracorporeal immunoadsorption (EIA) of anti-Galalpha1,3Gal (Gal) antibody was carried out. Maintenance therapy was with cobra venom factor, cyclosporine. mycophenolate mofetil, methylprednisolone and anti-CD154 mAb. Porcine islets were injected intraportally (14,000 and 32,000 IE/kg, respectively) and high-dose pig mobilized peripheral blood progenitor cells (3 x 10(10) cells/kg) were infused into a systemic vein. Porcine islets were also implanted in the sternomastoid muscle to facilitate subsequent biopsies. In both groups. porcine C-peptide was measured, and histological examination of liver or sternomastoid muscle biopsies was performed at regular intervals. In Group 1, total pancreatectomy reduccd human C-peptide to < 0.1 ng/ml and induced insulin-requiring diabetes. The transplantation of porcine islets was followed by normalization of glycemia for 15-24 h. Porcine C-peptide was detected only transiently immediately after porcine islet injection (maximum 0.12 ng/ml). Histological examination of liver biopsies taken between days 2 and 19 did not reveal viable islets, but necrotic cell structures with mononuclear cell infiltrates were identified in portal venules. In Group 2, injection of porcine islets into non-pancreatectomized recipients induced a transient hypoglycemia (2-4 h) requiring concentrated intravenous dextrose administration. Porcine C-peptide was detectable for 5 and 3 days (maximum 2.8 and 1.0 ng/ml), respectively. Baboon #4 died on day 12 from small bowel intussusception. Liver and sternomastoid muscle biopsies showed well-preserved porcine islets, staining positive for insulin and glucacon, without signs of rejection. In baboon #5, viable islets were detected in the sternomastoid muscle biopsy on day 14, but not on day 28 or thereafter. A progressive mononuclear cell and macrophage infiltration was seen in the biopsies. In conclusion, conventional immunosuppression allowed survival of porcine islets in baboons for < 24 h. The non-myeloablative regimen prolonged survival of porcine islets for > 14 days. However, despite depletion of T cells, anti-Gal antibody and complement, and CD154-hlockade, porcine islets were rejected by day 28. These results suggest that powerful innate immune responses are involved in rejection of discordant xenogencic islets.

Animals↗
PubMed2001

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Adult↗
PubMed2001

Dose optimization of mycophenolate mofetil when administered with a low dose of tacrolimus in cadaveric renal transplant recipients.

BACKGROUND: Supplementation of immunosuppressive therapy with mycophenolate mofetil (MMF) has been found to reduce the rate of acute rejection in renal transplantation. We report a dose-finding study for MMF when administered in combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric renal transplant recipients. METHODS: Two hundred thirty-two patients at 16 centers were enrolled in this randomized, parallel-group study. The three treatment groups were tacrolimus and corticosteroids (MMF-0 group, n=82); tacrolimus, corticosteroids, and 1 g of MMF daily (MMF-1 g group, n=79); and tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71). Study duration was 6 months, and patients were followed up for patient and graft survival for 12 months. RESULTS: At 6 months posttransplantation, daily doses of 1 g and 2 g of MMF were associated with significantly lower rates of acute rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%, 24.9%, and 22.9%, respectively, for the three treatment groups when acute rejection was determined by clinical criteria (P=0.007). At month 12, patient survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%, 92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group, respectively. Gastrointestinal adverse events and leukopenia were higher in the MMF groups, especially in the MMF-2 g group (P<0.05). CONCLUSIONS: Low-dose tacrolimus combined with a MMF dose of 1 g daily and corticosteroids provided an optimized efficacy and safety profile. A higher dose of MMF (2 g) was associated with greater toxicity without a significant improvement in efficacy.

Adrenal Cortex Hormones↗
PubMed2001

Video-assisted neck exploration for primary and secondary hyperparathyroidism: initial experience.

BACKGROUND: Minimally invasive surgery (MIS) for primary hyperparathyroidism includes unilateral neck exploration, access via a totally endoscopic approach, and access via a video-assisted procedure. We report herein our initial experience with the video-assisted neck exploration procedure for primary (PHPT) and secondary hyperparathyroidism (SHPT). METHODS: Between June 1999 and May 2000, 35 patients were selected for PHPT (n = 25) and SHPT (n = 10). In all cases, video-assisted neck exploration was performed under general anesthesia, leading to selective adenoma removal in PHPT or subtotal parathyroid resection in SHPT. Patient selection was based on the preoperative localization studies (ultrasonography and sestamibi scintigraphy). RESULTS: Five of the 25 patients operated on for PHPT (20%) and three of the 10 patients who underwent surgery for SHPT (30 %) were converted to a conventional surgical technique. The mean operative times in PHPT and SHPT were 48.9 +/- 18.7 min and 136.8 +/- 18.7 min, respectively. The recurrent laryngeal nerve was identified in 45% of the patients. The median size and weight of the resected parathyroid glands were 1.8 cm (range, 0.9-2.5) and 1 g (range, 0.5-7), respectively. The length of skin incision was 24 +/- 1.2 mm. All but one patient are currently cured, with a median follow-up of 6 months (range, 2-13). Postoperative complications included hematoma and transient hoarseness in one patient each (2.85%). The median pain intensity, based on the visual analogue scale (VAS) method, as measured at postoperative day 1 was 0.5 (range, 0-3.6). In the PHPT group, the postoperative hospital stay was

Adult↗
PubMed2001

Minimally invasive video-assisted approach for partial and total thyroidectomy: initial experience.

BACKGROUND: We report our initial experience with partial and total thyroidectomy using a video-assisted approach. The feasibility, safety, and potential benefits of this technique are examined. METHODS: Between January and May 2000, 28 patients were select to undergo a thyroid lobectomy (n = 17) or total thyroidectomy (n = 11) by a video-assisted cervical approach. Patient selection was based on clinical examination and preoperative ultrasonography. The surgical procedures were conducted under general anesthesia through a minimal substernal skin incision. Frozen sections were examined peroperatively in all cases. RESULTS: The initial diagnosis was solitary nodule in 19 patients and multinodular goiter in 8 patients. One patient was treated for hyperthyroidism. The mean cranio-caudal axis and transverse diameter of the resected specimen were 4.9 +/- 0.9 and 2.7 +/- 0.5 cm, respectively, and the mean total lobar weight was 11.9 +/- 5.5 g. Conversion to conventional surgery was required in three patients (10.7%), due to local bleeding in all cases. The mean operative times were 150 +/- 8.2 and 102.5 +/- 17 min for total and partial thyroidectomy, respectively. The laryngeal nerve was identified in 94.8% of cases. The mean length of skin incision was 25.4 +/- 2 mm. There was one case of postoperative hypocalcemia and one case of postoperative hoarseness. One patient had a transient vocal cord palsy. The postoperative hospital stay was 1 day for 66.7% of patients. The pain intensity evaluation, performed on postoperative day 1 using the visual analogue scale (VAS) method, was 1.9 +/- 1.4. CONCLUSION: Video-assisted thyroidectomy is feasible, safe, and effective in selected cases. Benefits for the patients in terms of postoperative pain, hospital stay, and cosmesis still need to be assessed in a prospective trial comparing standard open and video-assisted approaches.

Adult↗
PubMed2001

Increase of physical activity level after successful renal transplantation: a 5 year follow-up study.

BACKGROUND: Physical activity (PA) level of end-stage renal disease (ESRD) patients after renal transplantation (TP) is a largely unexplored field, although it is an important component of quality of life. METHODS: Using the Baecke self-administered and the Five-City Project 7-day PA recall questionnaires, PA level was estimated in 32 consecutive ESRD patients (12 males, 20 females; mean age 45.9+/-13.1 years; mean dialysis duration 23.5+/-21.8 months) admitted for renal TP and to whom no exercise programme of any kind was proposed. PA were recorded 1, 3, 6, 12 and 60 months after TP. RESULTS: Immediate pre-TP PA level of renal transplant candidates was between 18 and 35% less than that of age-matched healthy subjects (P < 0.05), depending on gender and questionnaire. After an immediate decrease in PA level 1 month post-TP, mean PA level increased and reached a plateau 1 year after TP. This gain in PA capacity reached 30%, as compared with pre-TP values (P = 0.06 to P < 0.01). During the fifth year after TP, the mean level of PA was unchanged. A more qualitative analysis, allowed by the sub-score comparisons, showed that although the occupational status of the patients remained the same, they participated significantly more in moderate and even high intensity PA (leisure, sports, household chores) after TP. CONCLUSIONS: Most renal graft recipients are spontaneously more active after TP, an observation consistent with a better quality of life. Therefore, they should be advised precisely about how to resume more strenuous activities such as sports in order to avoid cardiac or musculoskeletal disorders in relation to their weakened pre-TP condition.

Adult↗
PubMed2001

Outcome of cadaver kidney transplantation in 23 patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (DM) is a growing cause of end-stage renal failure worldwide. Yet, only a minority of type 2 diabetics are considered today for kidney transplantation (KT). The scarcity of data on the outcome of such patients after KT prompted us to review our experience. METHODS: Between 1 January 1983 and 30 June 1996, 23 patients with type 2 DM received a first cadaver KT at a mean age of 57+/-9 (41-73) years, after a dialysis period ranging from 5 to 72 (mean 25+/-18) months. Only nine patients had a history of coronary and/or peripheral vascular disease before KT. All were given cyclosporin- or tacrolimus-based immunosuppression. Post-KT follow-up ranged from 4 to 181 (mean 70+/-38) months. Outcome analysis focused on the impact of cardiovascular complications. RESULTS: Patient survival at 1, 5 and 8 years was 91, 83 and 76% respectively. Death was due to infection in three patients and to a cardiovascular event in two. The actuarial risk of coronary, cerebrovascular, peripheral vascular, and any cardiovascular event after KT was 14, 13, 9 and 30% at 1 year, 20, 13, 50 and 58% at 5 years, and 20, 46, 66 and 72% at 8 years respectively. Post-KT hospital readmissions averaged 10 days/patient-year and were mostly related to the management of peripheral vascular disease. CONCLUSION: KT is an excellent therapeutic option for selected patients with type 2 DM. Peripheral vascular disease is the leading cause of morbidity following KT. KT should be considered in type 2 diabetics with a low/medium cardiovascular risk.

Adult↗
PubMed2001

Correlation of mycophenolic acid pharmacokinetic parameters with side effects in kidney transplant patients treated with mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil (MMF) is widely used in organ transplantation to prevent acute rejection. Because MMF can produce hematologic and/or gastrointestinal toxicity, therapeutic monitoring is becoming mandatory. This study was designed to investigate the relationship between the clinical events and the pharmacokinetics of mycophenolic acid (MPA) in adult renal transplantation. METHODS: Thirty-one adult kidney recipients were prospectively included in the study. MPA pharmacokinetic profiles (blood sampling at 0, 0.5, 1, 2, 4, 6, and 12 h after MMF oral dose) were obtained after transplantation (desired creatinine clearance, 40 mL/min), at 3 months after grafting, and at every clinical event (e.g., side effect or rejection). All patients received a 10-day course of anti-thymocyte globulin, cyclosporine, MMF (1 g twice daily), and steroids. RESULTS: We divided the 31 patients into two groups (groups 1 and 2). Ten patients (32%; group 1) had uneventful outcomes, and 21 patients (68%; group 2) presented with MPA-related side effects. For groups 1 and 2, the MPA trough concentrations (C(min)) were 1.63 +/- 1.07 and 2.29 +/- 1.16 mg/L, respectively (P = 0.06), and the areas under the curve (AUCs) for MPA from t(0) to t(12 h) (MPA-AUC(0-12h)) were 39.80 +/- 15.29 and 62.10 +/- 21.07 mg. h/L, respectively (P = 0.0005, two-sample t-test). Three patients experienced acute graft rejection after the oral MMF dose was reduced because of side effects. In this group, the MPA-C(min) and MPA-AUC were significantly lower by the time acute rejection occurred (1.00 +/- 0.45 mg/L and 25.00 +/- 6.20 mg. h/L, respectively). At a fixed dose (1 g twice per day), we compared the pharmacokinetic parameters of MPA [C(min), the MPA concentration 30 min after the oral dose of MMF (C(30)), and AUC] according to the presence or absence of side effects in the two groups. C:(min) and AUC did not differ between the two groups [C(min) = 2.22 +/- 1.13 vs 2.17 +/- 1.13 mg/L (P = 0.9); AUC = 66.82 +/- 29.87 vs 55.70 +/- 11.74 mg. h/L (P = 0.11)]; and C(30) was significantly higher in group 2 than in group 1 (C(30) = 32.99 +/- 12.59 vs 7.45 +/- 5.40 mg/L; P <0.0001). CONCLUSIONS: Our results demonstrate a pharmacokinetic/pharmacodynamic relationship between MPA and clinical events. At a fixed dose of 2 g/day, a high C(30) is associated with increased risk for side effects. This study suggests that dividing the MMF daily oral dose into more than two divided doses might prevent early MPA toxicity.

Adolescent↗
PubMed2001

Pharmacokinetic basis for the efficient and safe use of low-dose mycophenolate mofetil in combination with tacrolimus in kidney transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) is an effective posttransplantation immunosuppressive agent used in combination with cyclosporin A (CsA) or tacrolimus (Tc). An increase in plasma mycophenolic acid (MPA) has been shown in patients receiving Tc-MMF combination therapy compared with CsA-MMF combination therapy at the same dose of MMF. The aim of this prospective study was to assess the pharmacokinetic/pharmacodynamic (PK/PD) relationship for MPA in kidney transplant patients receiving low-dose MMF (500 mg twice a day) in combination with Tc. METHODS: Adult kidney transplant recipients (n = 51) were included. MPA-PK profiles (blood sampling at 0, 0.5, 1, 2, 4, 6, and 12 h after MMF oral dose) were obtained within the first 2 weeks after transplantation, 3 months after grafting, and at every adverse clinical event [side effect or acute rejection (AR)]. All patients received Tc, MMF (500 mg twice a day), and steroids. RESULTS: Thirty patients (59%) had uneventful outcomes, and 21 patients had 33 episodes of MPA-related side effects; only 3 patients had AR. A total of 78 MPA-PK profiles were obtained. The following PK parameters were increased in the side-effects group compared with the non-side effects group: mean MPA c(min), 2.63 +/- 1.58 vs 1.75 +/- 0.82 mg/L (P = 0.016); mean c(30), 10.47 +/- 6.27 vs 7.66 +/- 8.95 mg/L (P = 0.009); mean c(60), 9.67 +/- 5.42 vs 5.83 +/- 2.6 mg/L (P = 0.0002); mean area under the MPA time-concentration curve from 0 to 12 h [MPA-AUC((0-12))], 48.38 +/- 18.5 vs 36.04 +/- 10.82 mg. h/L (P = 0.0006); mean dose-normalized MPA-AUC, 0.16 +/- 0.05 vs 0.12 +/- 0.04 (mg. h/L)/(mg/m(2)) (P = 0.0015). For the three AR patients, MPA concentrations obtained at the time of AR revealed MPA c(min) values of 1.86, 1.76, and 3.83 mg/L, respectively, and MPA-AUC((0-12)) values of 37.7, 24.9, and 104.9 mg. h/L. The threshold of toxicity was 3 mg/L (sensitivity, 38.7%; specificity, 91.5%) for c(min), 8.09 mg/L for maximum MPA concentration during the first hour (sensitivity, 77.8%; specificity, 67.4%), and 37.6 mg. h/L for MPA-AUC((0-12)) (sensitivity, 83.3%; specificity, 59.6%). CONCLUSIONS: These results demonstrate the relationship between plasma MPA concentrations and toxicity. High c(min), c(30), and c(60) values as well as AUC((0-12)) are associated with increased risk for side effects. These values may have an importance in a routine monitoring program.

Adult↗
PubMed2000

Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients.

INTRODUCTION: A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) in a triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of acute rejection was similar (approximately 40%) with a trend for better renal function with sirolimus. METHODS: In 14 European centers, first cadaveric renal allograft recipients were randomized to receive sirolimus (n = 40) or CsA (n = 38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of mycophenolic acid and prednisolone were also measured. RESULTS: At 12 months, graft survival (92.5% sirolimus vs. 89.5% CsA), patient survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-proven acute rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients received bolus steroid therapy (20 vs. 11, P = 0.068). From month 2 onward, the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients. The adverse events reported more frequently with sirolimus were thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA group, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytomegalovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed significantly more often. DISCUSSION: Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA, whereas safety profiles were different. These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection.

Acute Disease↗
PubMed2000

The experimental (in vitro) and clinical (in vivo) immunosuppressive effects of a rat IgG2b anti-human CD2 mAb, LO-CD2a/BTI-322.

BACKGROUND: CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells, working as a cell adhesion and costimulatory molecule. The aim of this paper is to analyze the mechanism of action of a rat IgG2b anti-human CD2 monoclonal antibody (mAb) (LO-CD2a/BTI-322 mAb), which is a potent immunosuppressive agent and inducer of cell death. In vivo, this mAb is able to prevent or treat kidney allograft rejection. METHODS: The mechanisms by which the LO-CD2a/BTI-322 mAb is able to induce inhibition of cell activation and cell death were analyzed by mixed lymphocyte reactions and by flow cytometry. After in vivo treatment, levels of circulating mAb were measured by ELISA as well as anti-rat immunization and cytokine release. RESULTS: We show that the inhibition of cell activation induced by LO-CD2a/BTI-322 mAb after allogeneic or OKT3 stimulation is due to an Fcgamma receptor-dependent CD2 down-modulation and to T-cell depletion through an antibody-dependent cell-mediated cytotoxicity mechanism mediated by NK cells or activated monocytes. Peripheral T- and NK-cell depletion was observed after in vivo treatment with LO-CD2a/BTI322. Cytokine release (TNFalpha) was correlated with some side effects, but only after the first injection, and the effects were never severe or life threatening. CONCLUSION: The correlation between the in vitro and in vivo data suggests that T-cell depletion, especially of activated cells, and inhibition of cell activation after CD2 down-modulation are the main mechanisms of action of the LO-CD2a/BTI-322 mAb.

Animals↗
PubMed2000

Laparoscopic and open live donor nephrectomy: a cost/benefit study.

Recently, laparoscopic liver-donor nephrectomy has been developed in order to increase organ donation. In this study we compare and review the records of 10 donors operated by open extraperitoneal approach and of 10 donors operated by a laparoscopic transperitoneal approach (LSC). Results show less use of postoperative parenteral narcotics in the LSC group (109 mg vs 272 mg; P < 0.0005) than in the extraperitoneal group. Morbidity was similar in both groups. There was no difference in postoperative stay. Allograft kidney function was similar in both groups until 6 months after donation. The use of disposable laparoscopic material bears an extra cost of 900 US$. We can thus conclude that laparoscopic live-donor nephrectomy is a safe procedure that significantly reduces postoperative pain, and is not detrimental to the allograft. The total cost of the laparoscopic procedure will be lower than that of the open approach if the length of postoperative stay is cut by 3 days.

Adult↗