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Biomedical subjects

P Morel

Publications and source records attributed to P Morel.

At least 37 records · Page 2Linked to original sources
PubMed2006

Sequential kidney/islet transplantation: efficacy and safety assessment of a steroid-free immunosuppression protocol.

The aim of this study was to assess the efficiency and safety of the Edmonton immunosuppression protocol in recipients of islet-after-kidney (IAK) grafts. Fifteen islet infusions were administered to 8 patients with type 1 diabetes and a functioning kidney graft. Immunosuppression was switched on the day of transplantation to a regimen associating sirolimus-tacrolimus-daclizumab. Insulin-independence was achieved in all patients for at least 3 months, with an actual rate of 71% at 1 year after transplantation (5 of 7 patients). After 24-month mean follow-up, five have ongoing insulin independence, 11-34 months after transplantation, with normal HbA1c, fructosamine and mean amplitude of glycemic excursions (MAGE) values. Results of arginine-stimulation tests improved over time, mostly after the second islet infusion. Severe adverse events included bleeding after percutaneous portal access (n=2), severe pneumonia attributed to sirolimus toxicity (n=1), kidney graft loss after immunosuppression discontinuation (n=1), reversible humoral kidney rejection (n=1) and fever of unknown origin (n=1). These data indicate that the Edmonton approach can be successfully applied to the IAK setting. This procedure is associated with significant side effects and only patients with stable function of the kidney graft should be considered. The net harm versus benefit has not yet been established and will require further studies with larger numbers of enrolled subjects.

Adrenal Cortex Hormones↗
PubMed2006

Hepatopulmonary syndrome increases the postoperative mortality rate following liver transplantation: a prospective study in 90 patients.

Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of patients with end-stage liver diseases. HPS is diagnosed by hypoxemia and pulmonary vascular dilatation and is an independent risk factor of mortality. Orthotopic liver transplantation (OLT) is the only factor that modifies the natural course of HPS. Once patients with HPS have been transplanted, their long-term survival rate is similar to transplanted patients without HPS. Consequently, HPS is an indication of OLT whatever the severity of hypoxemia. However, besides the favorable long-term survival of HPS patients with OLT, a high postoperative mortality (mostly within 6 months) has been suggested. The aim of our study was to analyze the incidence of HPS and postoperative outcome after OLT in 90 consecutive patients. All patients were prospectively included and had blood gas analysis to detect HPS. Patients with hypoxemia had contrast echocardiography to confirm HPS. Nine patients had HPS with a 50 </= PaO(2)</= 70 mmHg. Among them 3 (33%) died while the mortality rate was 9.2% in the group without HPS (7 over 76 patients). In the HPS patients who survived, the syndrome completely recovered within 6 months. In conclusion, our study shows a high postoperative mortality rate following OLT even though the preoperative PaO(2) was >50 mmHg in all HPS patients transplanted.

Adult↗
PubMed2006

Detection of insulin mRNA in the peripheral blood after human islet transplantion predicts deterioration of metabolic control.

Recent updates of the Edmonton trial have shown that insulin independence is progressively lost in approximately 90% of islet transplant recipients over the first 5 years. Early prediction of islet graft injury could prompt the implementation of strategies attempting to salvage the transplanted islets. We hypothesize that islet damage is associated with the release and detection of insulin mRNA in the circulating blood. Whole blood samples were prospectively taken from 19 patients with type 1 diabetes receiving 31 islet transplants, immediately prior to transplantation and at regular time-points thereafter. After RNA extraction, levels of insulin mRNA were determined by quantitative reverse tran-scriptase-polymerase chain reaction. All patients exhibited a primary peak of insulin mRNA immediately after transplantation, without correlation of duration and amplitude with graft size or outcome. Twenty-five subsequent peaks were observed during the follow-up of 17 transplantations. Fourteen secondary peaks (56%) were closely followed by events related to islet graft function. Duration and amplitude of peaks were higher when they heralded occurrence of an adverse event. Peaks of insulin mRNA can be detected and are often associated with alterations of islet graft function. These data suggest that insulin mRNA detection in the peripheral blood is a promising method for the prediction of islet graft damage.

Adult↗
PubMed2006

Virological, serological and epidemiological study of 255 consecutive cases of genital herpes in a sexually transmitted disease clinic of Paris (France): a prospective study.

Some studies (mostly retrospective) have pointed to an increasing frequency (up to 60%) of herpes simplex virus type 1 (HSV-1) in genital herpes (GH), but they were biased towards severe or atypical cases. We wished to evaluate the frequency of HSV-1 in patients attending our clinic for both first and recurrent episodes of GH. All patients (men and women) with genital lesions compatible with GH were included in a prospective study between May 1999 and April 2002. For all patients a standardized questionnaire, clinical examination, MRC5 culture (Dade Behring), polymerase chain reaction (PCR)-herpes consensus (Argène Biosoft) in case of negative culture and type-specific herpes serology HSV-1 and HSV-2 (Elisa Eurobio) were obtained. Predictive factors associated with HSV-1 and HSV-2 GH were studied by uni- and multivariable analyses. In all, 255 patients had a positive culture (n = 216) or PCR (n = 39). A total of 248 patients had typable herpes (148 men and 100 women). Median age was 33 (27-43); 20% had anal herpes; 48% had clinically recurrent lesions; 21% were HIV +; 20% of men were homosexual; 77% practised oral sex. In all, 36 were HSV-1 (14.5%): more in women, 25/100 (25%), than in men, 11/148 (7.5%) (odds ratio [OR]: 4 [1.8-9.1], P = 0.008). HSV-1 accounted for 23% of cases of first clinical episodes (women: 31.5%; men: 14.7%) (P = 0.02) and 6% of clinically recurrent episodes (women: 15%; men: 1.2%) (OR: 3.8 [1.6-9.1], P = 0.0033). Serological study was done in 239: primary infection was disclosed in 33 (HSV-1: 61%), HSV-2 non-primary first episode in 22 and recurrence in 184 (HSV-1: 8%). In all, 37% of recurrent episodes presented as a first clinical episode. HSV-1 was linked in men with homosexuality (P<0.01) and anilingus (P<0.01), in women with younger age (P<0.01), more sexual intercourses (P<0.0001) and more oral sex (P<0.001). Although HSV-1 is frequent in first clinical (23%) and primary (61%) episodes of GH, recurrent GH remains mostly due to HSV-2 (94%).

Adult↗
PubMed2006

Preoperative work-up in asymptomatic patients undergoing Roux-en-Y gastric bypass: is endoscopy mandatory?

BACKGROUND: We aimed to determine before Roux-en-Y gastric bypass (RYGBP) in asymptomatic morbidly obese patients: 1) the prevalence of abnormal findings at upper gastrointestinal (UGI) endoscopy; 2) Helicobacter pylori (HP) status; 3) clinical consequences of these findings; and 4) associated costs. METHODS: We retrospectively reviewed 468 consecutive patients, excluded those with UGI symptoms, drug intake or previous UGI endoscopy/surgery, and analyzed findings in the 319 remaining patients (68%). RESULTS: There were abnormal findings in 147 patients (46%), including 54 hiatal hernias and 146 parietal (i.e. mucosal or submucosal) lesions. The most significant were 7 ulcers and 2 gastric polyposis. HP was detected (using CLO-test) in 124 patients (39%). Histopathological examination of biopsies was abnormal in 109/161 patients (68%), and disclosed mainly chronic gastritis (n=98). Abnormal findings were more frequent in HP-positive compared to HP-negative patients (94 vs 51%, P<0.001). Findings had clinical implications in only 4% of patients: delayed surgery (7 ulcers), prophylactic gastrectomy (2 gastric polyposis), unnecessary work-up (3 irrelevant/false-positive diagnoses), and inclusion in a screening program (1 Barrett's esophagus). Mean cost of complete UGI work-up was 389 euro/patient. CONCLUSION: Asymptomatic morbidly obese patients frequently harbour UGI lesions warranting UGI work-up before RYGBP. However, routine endoscopy presents drawbacks. We propose a less invasive strategy which reduces costs and limits false-positive results and the subsequent investigations that they require. In our series, it would have missed two gastric polyposis only, for which no formal recommendation has yet been issued. This strategy could be a valuable alternative to routine UGI endoscopy before RYGBP in asymptomatic patients.

Adult↗
PubMed2005

Impact of chronic oral anticoagulation on management and outcomes of patients with acute myocardial infarction: data from the RICO survey.

OBJECTIVE: To determine the prevalence of chronic oral anticoagulant drug treatment (COA) among patients with acute myocardial infarction (AMI) and its impact on management and outcome. METHODS: All patients with ST segment elevation AMI on the RICO (a French regional survey for AMI) database were included in this analysis. COA was defined as continuous use >or= 48 hours before AMI. RESULTS: Among the 2112 patients with ST elevation myocardial infarction (STEMI), 93 (4%) patients were receiving COA. These patients were older and more likely to have a history of hypertension, diabetes and prior myocardial infarction than patients without COA. In addition, fewer patients who received COA underwent reperfusion therapy or received an antiplatelet agent (aspirin/thienopyridines). Moreover, patients receiving COA experienced a higher incidence of in-hospital major adverse events (death, recurrent myocardial infarction or major bleeding, p = 0.005). Multivariate analysis showed that only ejection fraction, current smoking and multiple vessel disease, but not COA, were independent predictive factors for major adverse events. In contrast, COA was an independent predictive factor for heart failure when adjusted for age, diabetes, creatinine clearance, reperfusion, heparin and glycoprotein IIb/IIIa inhibitors (odds ratio 2.06, CI 95% 1.23 to 3.43, p = 0.005). CONCLUSION: In this population based registry, patients with STEMI with prior use of COA constituted a fairly large group (4%) with an overall higher baseline risk profile than that of patients without COA. Fewer in the COA group received reperfusion therapy or aggressive antithrombotic treatment and they experienced more adverse in-hospital outcomes. Thus, further studies are warranted to develop specific management strategies for this high risk group.

Administration, Oral↗
PubMed2005

Low-dose oral microemulsion ciclosporin for severe, refractory ulcerative colitis.

BACKGROUND: The optimal modalities of treatment with oral microemulsion ciclosporin in patients with severe, steroid-refractory ulcerative colitis are uncertain. AIM: To assess the applicability, in terms of efficacy and tolerability, of a standard oral microemulsion ciclosporin treatment protocol targeting relatively low blood ciclosporin concentrations, in patients with severe, steroid-resistant ulcerative colitis. PATIENTS AND METHODS: Patients with a severe attack of ulcerative colitis and no satisfactory response to intravenous corticosteroids were started on oral microemulsion ciclosporin. Dosages were adapted according to a standard protocol, targeting a blood predose ciclosporin concentration (C0) of 100-200 ng/mL. Patients without a clinical response on day 8 were scheduled for colectomy. RESULTS: Sixteen patients were enrolled. A clinical response was observed in 14/16 (88%). The mean clinical activity index scores and concentrations of C-reactive protein on days 0, 4 and 8 were 11.8, 6.7 and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0-8) was 149 pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min. One patient had an acute elevation of transaminases that resulted in discontinuing ciclosporin. CONCLUSIONS: Even when dosed for a target C0 of 100-200 ng/mL, oral microemulsion ciclosporin for severe, steroid-refractory ulcerative colitis achieves an efficacy similar to that attained with higher, potentially more toxic levels. The oral route should replace intravenous treatment in this clinical setting.

Administration, Oral↗
PubMed2005

The effect of insulin on cardiac autonomic balance predicts weight reduction after gastric bypass.

AIMS/HYPOTHESIS: The aim of this study was to assess the predictive role of autonomic reactivity in body weight loss induced by gastric bypass. METHODS: A group of 22 morbidly obese subjects, who were due to undergo a gastric bypass, were submitted, before surgery, to a euglycaemic-hyperinsulinaemic clamp, during which a continuous recording of the ECG was performed. The effect of insulin on cardiac autonomic balance was evaluated by performing power spectral analysis of heart rate variability. The low-to-high frequency ratio was calculated before and during the clamp and its modifications were expressed as % delta low-to-high frequency ratio (%Delta L: H). RESULTS: Preoperative %Delta L: H showed a significant (p=0.0009, r2=0.43), positive relationship to the reduction of body weight, measured 1 year after surgery and expressed as % excess weight loss (% EWL). Preoperative BMI was also significantly (p=0.0009, r2=0.43) negatively related to the 12-month % EWL. In a multiple regression analysis, %Delta L: H remained a significant (p=0.003), independent predictor of body weight loss, even when preoperative BMI or age, % fat mass, insulinaemia and glucose disposal were taken into account. CONCLUSIONS/INTERPRETATION: The best correction of excess body weight was achieved by those obese subjects who had a preserved capacity to shift their cardiac autonomic balance towards a sympathetic prevalence in response to an euglycaemic-hyperinsulinaemic clamp. Further studies are needed to elucidate the mechanisms through which the autonomic nervous system influences weight reduction.

Adult↗
PubMed2005

Randomized clinical trial of mechanical bowel preparation versus no preparation before elective left-sided colorectal surgery.

BACKGROUND: Mechanical bowel preparation (MBP) is performed routinely before colorectal surgery to reduce the risk of postoperative infectious complications. The aim of this randomized clinical trial was to compare the outcome of patients who underwent elective left-sided colorectal surgery with or without MBP. METHODS: Patients scheduled for elective left-sided colorectal resection with primary anastomosis were randomized to preoperative MBP (3 litres of polyethylene glycol) (group 1) or surgery without MBP (group 2). Postoperative abdominal infectious complications and extra-abdominal morbidity were recorded prospectively. RESULTS: One hundred and fifty-three patients were included in the study, 78 in group 1 and 75 in group 2. Demographic, clinical and treatment characteristics did not differ significantly between the two groups. The overall rate of abdominal infectious complications (anastomotic leak, intra-abdominal abscess, peritonitis and wound infection) was 22 per cent in group 1 and 8 per cent in group 2 (P = 0.028). Anastomotic leak occurred in five patients (6 per cent) in group 1 and one (1 per cent) in group 2 (P = 0.210) [corrected] Extra-abdominal morbidity rates were 24 and 11 per cent respectively (P = 0.034). Hospital stay was longer for patients who had MBP (mean(s.d.) 14.9(13.1) versus 9.9(3.8) days; P = 0.024). CONCLUSION: Elective left-sided colorectal surgery without MBP is safe and is associated with reduced postoperative morbidity.

Adult↗
PubMed2005

[Bacterial detection leading to pathogen inactivation].

Bacterial contamination of blood components remains the highest infectious risk in blood transfusion, the risk is particularly high when it affects platelet concentrates (PC). In France, the residual risk of transfusion reaction due to bacterial contamination of PC has been decreasing slowly since 1994 but for all severity 1 case occurs with about 25,000 distributed PC and one death occurs with 200,000 distributed units. This reduction of the risk may be due to the measures which were implemented during the last 10 years in order to prevent contamination during donation. Improving strategies for reducing the risks of bacterial contamination is one of the priorities of the French National Blood Transfusion Service (l'Etablissement Français du sang - EFS). The main target remains PC. Bacterial detection or pathogens inactivation are now available and are able to reduce (for detection) or prevent (for inactivation) the occurrence of reaction due to bacterial contamination of PC. Up to now, the choice is in favour of bacterial detection. A national study was carried out in seven regional EFS at the end of 2004. It aims at confirming the feasibility of a systematic bacterial screening of PC before their delivery. The first conclusions show that this screening can be implemented with acceptable modifications in term of platelets availability. We can expect in a next future that new pathogens reduction technique and/or new detection systems will be available, certainly more efficient to prevent reaction due to bacterial contamination. Implementation of actual detection methods is probably a temporary solution.

Bacteriological Techniques↗
PubMed2005

[Towards bacterial detection in labile blood products].

Bacterial contamination of blood components represents today the highest infectious risk in blood transfusion, the risk is particularly high when it affects platelet concentrates. The prevention methods developed over the past ten years (donor selection, phlebotomy site preparation, first 30 ml diversion, systematic leuko-reduction...) which aimed at limiting the introduction of bacteria in donations and bacterial proliferation, has reduced the risk of transfusion reaction due to the bacterial contamination. Improving strategies for reducing the risks of bacterial contamination is one of the priorities of the French National Blood Transfusion Service (l'Etablissement français du sang - EFS). It is essential to improve existent prevention methods and develop the implication of all the actors (from donation to transfusion) involved in the prevention of this risk. Bacterial detection or pathogens inactivation are now available and are able to reduce (for detection) or prevent (for inactivation) the occurrence of reaction due to bacterial contamination of PC. Up to now, the choice is in favour of bacterial detection. Three methods (BacT/Alert, BioMerieux; eBDS, Pall; ScanSystem, Hemosystem) of detection of bacterial contamination in PC can be generalised now. Adaptations, need for their implementation are acceptable, especially concerning PC availability.

Automation↗
PubMed2005

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.

Creatinine↗
PubMed2005

Fludarabine plus cyclophosphamide in Waldenström's macroglobulinemia: results in 49 patients.

Fludarabine (FDR) therapy gives a response rate of about 30% in previously treated patients with Waldenström's macroglobulinemia (WM). The combination of FDR and cyclophosphamide (Cy) has been shown to be effective in chronic lymphoproliferative disorders. We administered the combination of FDR (30 mg/m2 i.v. D1-D3) and Cy (300 mg/m2 i.v. D1-D3) to 49 patients. Median age was 64 years. The median hemoglobin, albumin, beta 2 microglobulin and immunoglobulin M (IgM) levels were 9.9 g/100 ml, 39.6 g/l, 3 mg/l and 24.7 g/l, respectively. In all, 14 patients (29%) had not previously been treated. FDR/Cy was administered every 4 weeks for a median of four cycles. In all, 38 patients (77.6%) had partial responses, nine had stable disease and two had progressive disease. After a median of follow-up of 25 months, six patients relapsed and two patients developed large-cell lymphoma. The median time to treatment failure was 27 months. The main toxicity was hematological. In all, 12 patients died, four from progression, one from large-cell lymphoma, three from infection and four from a second malignancy. Two factors negatively influenced overall and event-free survival, age >65 years and IgM <40 g/l. The FDR/Cy combination, therefore, gives a high response rate in WM, even in previously treated patients with factors of poor prognosis.

Aged↗
PubMed2004

Waldenström's macroglobulinemia: prognostic factors and recent therapeutic advances.

Waldenström's macroglobulinemia is a rare B cell malignancy. All prognostic studies have identified the adverse prognostic effect of advanced age and low hemoglobin level for survival, whereas the prognostic value of a high level of monoclonal component remains controversial. Response to treatment is probably a favorable prognostic factor for overall survival. Conventional treatment is based on alkylating agents, and especially chlorambucil. Purine analogues, used initially for salvage treatment, are increasingly employed as front-line therapy. Purine analogues have not been compared with alkylating agents as first-line therapy in randomized trials, and it is unclear whether purine analogues extend survival. An anti-CD20 monoclonal antibody has given a response rate in about 30% of patients. Autologous and allogeneic stem cell transplantation may be considered for patients with refractory or relapsing disease.

Combined Modality Therapy↗
PubMed2004

Immunosuppression for pancreatic islet transplantation.

Protocols for islet transplantation have to take into account the diabetogenicity/islet toxicity of the immunosuppressive agents, namely corticosteroids and calcineurin inhibitors, most notably tacrolimus. The development by the Edmonton group of a sirolimus-based, steroid-free, low-tacrolimus regimen was a significant breakthrough that allowed the rate of insulin independence after islet transplantation to increase from 13% to 80% at 1 year. Drawbacks include the side effects of sirolimus and the reduction in insulin independence to 50% at 3 years, the latter being attributed to prolonged tacrolimus exposure. Currently explored alternatives to tacrolimus include cyclosporine, mycophenolate mofetil, and the novel agent FTY 720. Perspectives for the near future involve the achievement of "prope tolerance" by strategies using lymphocyte-depleting antibodies (anti-thymocyte globulin, campath-1H, hOKT3gamma1 [ala,ala]), or costimulatory blockade (anti-CD154 mAbs, CTLA4-Ig).

Cyclosporine↗
PubMed2004

Five-year follow-up after pediatric living related small bowel transplantation between two monozygotic twins.

Two 13-year-old monozygotic twins were used for living related small bowel transplantation (SBTx). The recipient presented with short gut syndrome secondary to complicated abdominal surgery. The indication for SBTx was based on a failure to thrive and a poor tolerance of TPN. The donor was an identical twin, as demonstrated by skin graft acceptance, which allowed performance of SBTx without immunosuppression. Growth charts were used to follow intestinal absorption functions and body composition. The donor was used as a control for the recipient. The recipient, who was transplanted with 160 cm of donor ileum, was discharged on postoperative day 62 on a regular diet. Before SBTx the recipient was 10 kg lighter in body weight than the donor, a gap that was progressively reduced over the follow-up period. A height deficit of 3 cm reversed within 1 year after SBTx. A 10-kg deficit in fat-free body mass was completely extinguished within 18 months. By 18 months posttransplant, recipient serum albumin and prealbumin were normal and comparable to donor values. d-Xylose absorption in the recipient remained lower than that in the donor. Within 6 months fecal fat excretion normalized in the recipient. d-Xylose absorption and fecal fat excretion were always within a normal range in the donor.

Adolescent↗