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P Feugier

Publications and source records attributed to P Feugier.

At least 19 recordsLinked to original sources
PubMed2006

Human umbilical vein endothelial cells increase ex vivo expansion of human CD34(+) PBPC through IL-6 secretion.

BACKGROUND: Ex vivo expansion of hematopoietic stem cells (HSC) can help reduce cytopenia following transplantation, especially in NHL patients whose BM is deficient because of extensive chemotherapy. We have previously reported that human umbilical vein endothelial cells (HUVEC) can contribute to improved PBPC expansion when used in co-culture with CD34(+) cells. METHODS: We evaluated the roles of direct HUVEC CD34(+) contact and HUVEC-produced soluble factors. We cultured CD34(+) PBPC harvested from NHL patients in four different conditions: (1) liquid culture without HUVEC; (2) co-culture in contact with HUVEC; (3) co-culture with HUVEC but without direct contact; (4) liquid culture with HUVEC-conditioned medium (CM). Thrombopoietin (Tpo), Flk2Flt3 ligand (FL) and c-kit ligand (KL) with or without rhIL-6 were added to these four culture conditions. RESULTS AND DISCUSSION: Our results showed that HUVEC co-culture or addition of HUVEC-CM to Tpo, FL and KL (TFK) improved CD34(+) PBPC expansion compared with liquid culture, as determined by total viable nucleated cells (TNC), colony-forming cell assay (CFC) and week-6 cobblestone area-forming cells (Wk-6 CAFC) expansions. Non-contact culture led to similar PBPC expansion as contact co-culture; moreover, HUVEC-CM improved PBPC expansion. However, when rhIL-6 was added to HUVEC-CM with TFK, no significant difference was observed. Finally, high quantities of IL-6 were detected in HUVEC-CM and addition of anti-IL-6 Ab inhibited the positive effect of HUVEC on PBPC expansion. Our results thus suggest that HUVEC may improve PBPC expansion, at least through IL-6 secretion.

Antigens, CD34↗
PubMed2005

Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: To analyze the long-term outcome of patients included in the Lymphome Non Hodgkinien study 98-5 (LNH98-5) comparing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) in elderly patients with diffuse large B-cell lymphoma. PATIENTS AND METHODS: LNH98-5 was a randomized study that included 399 previously untreated patients, age 60 to 80 years, with diffuse large B-cell lymphoma. Patients received eight cycles of classical CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.4 mg/m(2), and prednisone 40 mg/m(2) for 5 days) every 3 weeks. In R-CHOP, rituximab 375 mg/m(2) was administered the same day as CHOP. Survivals were analyzed using the intent-to-treat principle. RESULTS: Median follow-up is 5 years at present. Event-free survival, progression-free survival, disease-free survival, and overall survival remain statistically significant in favor of the combination of R-CHOP (P = .00002, P < .00001, P < .00031, and P < .0073, respectively, in the log-rank test). Patients with low-risk or high-risk lymphoma according to the age-adjusted International Prognostic Index have longer survivals if treated with the combination. No long-term toxicity appeared to be associated with the R-CHOP combination. CONCLUSION: Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma, with significant survival benefit maintained during a 5-year follow-up. This combination should become the standard for treating these patients.

Aged↗
PubMed2005

Attachment, morphology and adherence of human endothelial cells to vascular prosthesis materials under the action of shear stress.

In an effort to improve the long-term patency of vascular prostheses several groups now advocate seeding autologous endothelial cells (ECs) onto the lumen of the vessel prior to implantation, a procedure that involves pre-treating the prosthesis material with fibrin, collagen and/or other matrix molecules to promote cell attachment and retention. In this study, we examined the degree to which human umbilical venous endothelial cells (HUVECs) adhered to three materials commonly used polymeric vascular prosthesis that had been coated with the same commercial extra cellular matrix proteins, and after exposure to fluid shear stresses representative of femoro-distal bypass in a cone-and-plate shearing device. We quantified cell number, area of coverage and degree of cell spreading using image analysis techniques. The response of cells that adhered to the surface of each material, and following exposure to fluid shear stress, depended on surface treatment, topology and cell type. Whereas collagen coating improved primary cellular adhesion and coverage significantly, the degree of spreading depended on the underlying surface structure and on the application of the shear stress. In some cases, fewer than 30% of cells remained on the surface after only 1-h exposure to physiological levels of shear stress. The proportion of the surface that was covered by cells also decreased, despite an increase in the degree to which individual cells spread on exposure to shear stress. Moreover, the behaviour of HUVECs was distinct from that of fibroblasts, in that the human ECs were able to adapt to their environment by spreading to a much greater extent in response to shear. The quality of HUVEC attachment, as measured by extent of cell coverage and resistance to fluid shear stress, was greatest on expanded polytetrafluoroethylene samples that had been impregnated with Type I/III collagen.

Blood Vessel Prosthesis↗
PubMed2004

Prognostic factors in patients with aggressive non-Hodgkin's lymphoma treated by front-line autotransplantation after complete remission: a cohort study by the Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: Improved survival has been observed in aggressive non-Hodgkin's lymphoma (NHL) patients with adverse prognostic factors when autotransplantation (ASCT) was performed after complete remission. However, there is no agreement on the prognostic factors for patients treated with ASCT. We aimed to estimate the prognostic effect of clinical and biologic variables on relapse and survival rates by pooling the data from two trials. PATIENTS AND METHODS: Of the patients treated in the LNH87 and LNH93 trials, 330 under age 60 years achieved complete remission after high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone, and received consolidative ASCT; 16% of patients had T-cell NHL. The International Prognostic Index (IPI) score was 0 for 11%, 1 for 23%, 2 for 51%, and 3 for 15%. Univariate and Cox multivariate survival analyses were retrospectively performed on this population. RESULTS: Overall survival was 75 +/- 5% at 5 years and disease-free survival (DFS) 67 +/- 5%. For T-cell NHL, these scores were 54% and 44%, respectively. The IPI score had no prognostic value and only the following parameters adversely affected overall survival and DFS (P <.05): marrow involvement; more than one extranodal site; histology (nonanaplastic T-cell v others); and type of anthracycline (mitoxantrone v doxorubicin, for DFS only). CONCLUSION: These results suggest that ASCT can prevent relapse in patients with adverse IPI factors. However, patients presenting with a nonanaplastic T-cell phenotype, more than one extranodal site, or marrow involvement still have a higher risk of relapse. These factors should be taken into account when designing post-ASCT maintenance studies.

Adolescent↗
PubMed2004

[Ischaemia of the lower limbs: anaesthesia and intensive care].

OBJECTIVES: To appreciate the severity of a patient with acute limb ischaemia, to know how to manage these patients during the perioperative period. DATA SOURCES: References were obtained from PubMed data bank (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) using the following keywords: acute limb, ischaemia, prognosis, complications, rhabdomyolysis, hyperkalaemia, compartment syndrome, fasciotomy. DATA SYNTHESIS: Ischaemia of the lower limbs is a medico-surgical emergency. The ischaemia implies a decrease of cellular energetic stocks and an increase in intracellular calcium. During reperfusion, the calcium paradox is exacerbated and ROS formation produces membrane damage. Tissue oedema and a local and general inflammatory syndrome occur. Clinical symptoms of acute ischaemia include pallor, pulselessness, decrease of temperature and pain. Occurrence of neurological symptoms is a sign of severity. Prognosis of patients relates directly to preexisting collateral circulation, aetiology of the occlusion (thrombosis vs embolus), duration of ischaemia, topography of the occlusion (severity of proximal occlusions as the acute aortic occlusion), and co-morbidity (renal failure, heart failure). The temperature of the ischaemic limb, quality of the downstream circulation, extension of the thrombus, arterial pressure and association to a venous thrombosis are other prognostic factors of lower limb ischaemia. The first treatment to be initiated is high doses of heparin. Once the diagnosis is made, the number of preoperative tests will be as small as possible because of the urgency of revascularization. Arteriography will be performed only when really needed and when its realization will not delay revascularization and will not alter the patient's prognosis. Where general anesthesia is required, the choice of anaesthetic agents will be based on their haemodynamic stability. During severe acute limb ischaemia, monitoring of invasive pressure is recommended, as well as regular dosages of potassium, arterial gases and CPK. Preoperatively in case of severe ischaemia, (proximal occlusion lasting more than 6 hours), preventive treatment, including controlled reperfusion with heparinized serum is indicated. Surveillance and prevention of a rhabdomyolysis and renal failure are imperative. Immediately after reperfusion, a dosage of potassium must be performed; moreover that hyperkalaemia is favoured by acidosis or renal failure. Postoperative haemodialysis is performed in case of hyperkalaemia or renal failure. Occurrence of compartment syndrome has to be checked and fasciotomy must be performed in case of a doubt on the microcirculation integrity.

Acute Disease↗
PubMed2004

Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab.

BACKGROUND: The incidence of secondary central nervous system (CNS) occurrences in diffuse large-B-cell lymphoma is not sufficiently high to warrant the use of CNS prophylaxis in all patients. The addition of rituximab increases the complete response rate and prolongs event-free and overall survival in elderly patients with such lymphoma. PATIENTS AND METHODS: We analyzed a cohort of 399 elderly patients with lymphoma prospectively treated with eight cycles of CHOP with or without rituximab in order to assess if rituximab decreases the risk of CNS localization. Prophylaxis of CNS disease was not part of the treatment protocol. RESULTS: We observed 20 CNS occurrences: 12 on therapy, four after partial remission and four following complete remission. In three patients, the CNS was the only site of relapse. In a multivariate analysis, increased age-adjusted International Prognostic Index (IPI) was the only independent predictive factor of CNS recurrence. Only three of 20 patients are alive with a follow-up of 24 months. CONCLUSIONS: Rituximab did not influence the risk of CNS occurrence, possibly because of low rituximab diffusion. Direct intrathecal administration of rituximab could overcome this problem. We also confirmed that CNS occurrence is related to IPI as well as very poor prognosis of relapses occurring on therapy.

Aged↗
PubMed2004

All aggressive lymphoma subtypes do not share similar outcome after front-line autotransplantation: a matched-control analysis by the Groupe d'Etude des Lymphomes de l'Adulte (GELA).

BACKGROUND: Data are still conflicting on the indication of front-line autologous stem-cell transplantation (ASCT) as consolidation for aggressive lymphoma. To assess the therapeutic effect of ASCT among different aggressive lymphoma subtypes, we conducted a matched-control analysis by pooling the data from two Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. PATIENTS AND METHODS: Between October 1987 and September 1998, 330 patients received ASCT after achieving complete remission with the ACBVP induction regimen. The histological slides showed: B aggressive non-Hodgkin's lymphoma (B-NHL) in 249 patients (75%), T-NHL in 52 patients (15%) (including 23 T anaplastic) and non-classified NHL in 29 patients. The age-adjusted International Prognostic Index (aaIPI) was 2 or 3 in 66%. Patients were matched with controls from the same GELA database but treated with chemotherapy only. RESULTS: ASCT did not benefit non-anaplastic T-NHL patients [5-year overall survival (OS) 44% (chemotherapy) versus 49% (ASCT), P=0.87; disease-free survival (DFS) 38% versus 45%, P=0.89] in comparison with B-NHL [5-year OS 77% (chemotherapy) versus 79% (ASCT), P=0.64; DFS 67% versus 72%, P=0.13]. However, for B-NHL patients with aaIPI score 2 or 3, the benefit of ASCT was significant. CONCLUSIONS: This cohort study confirms the high efficacy of front-line ASCT in responding aggressive B-NHL patients with adverse prognostic factors.

Adolescent↗
PubMed2003

Complete recovery from Cryptosporidium parvum infection with gastroenteritis and sclerosing cholangitis after successful bone marrow transplantation in two brothers with X-linked hyper-IgM syndrome.

We describe two brothers who suffered from hyper-IgM syndrome (HIGM1) with similar clinical features: recurrent infections, especially cryptosporidium gastroenteritis with cholangitis. Their activated T cells did not express CD40L. Nucleotide sequencing revealed a mutation in both boys with respect to intron 4 and exon 5 boundaries of the CD40L gene in Xq26. They underwent successful bone marrow transplantation (BMT) from HLA-geno-identical siblings. The Cryptosporidium infection and cholangitis resolved thereafter. At 6 months after BMT, expression of CD40L on activated T lymphocytes was normal. After 1 year, both boys are well, and immune reconstitution has improved. Based on these two successful experiences, BMT with a genoidentical sibling seems a reasonable therapeutic approach for HIGM1, if Cryptosporidium infection occurs.

Animals↗
PubMed2003

CD34+ cells homing: quantitative expression of adhesion molecules and adhesion of CD34+ cells to endothelial cells exposed to shear stress.

To investigate the function of the main adhesion receptors (CD62L, CD49d, CD49e, CD11b and CD18) on CD34+ cells during homing, their expression was quantified by flow cytometry using calibration beads. CD34+ cells were isolated from bone-marrow (BM), cord blood (CB) or peripheral blood (PB) from patients with myeloma. As this process might mimic the mature leukocyte migration, we also observed the effect of exposing endothelial cells to shear stress (7 dyn/cm(2)) on the adhesion of CB CD34+ cells. The proportion of CD34+/CD62L+ cells was greater in PB than in BM (p<0.05). Likewise, we found a significantly greater expression of CD62L receptor on PB cells compared to BM cells (p<0.05) and on BM cells compared to CB cells (p<0.05). The proportions of CD34+/CD49d+ cells and CD34+/CD49e+ cells were significantly higher in the BM and CB than in PB. However, no significant difference in CD49d or CD49e antigen densities was observed. The beta_2 integrins (CD11b and CD18) receptors are also implicated in CD34+ cells homing to BM. No significant variation in CD34+/CD11b+ and CD34+/CD18+ cells frequency was noted. However quantitative analysis revealed that CD18 was more strongly expressed on BM cells than on PB and CB cells. The adhesion assay showed that fluid flow may favour a firm adhesion of CB CD34+ cells to endothelial cells whereas static conditions just allowed CD34+ cells sedimentation. In conclusion, quantitative expression of the main receptors on CD34+ cells indicates that the three main sources of CD34+ cells currently used for transplantation have neither the same phenotype nor the same number of antigenic sites for a receptor. So, we hypothesize that migrational capacity of these cells might be different. Moreover, it seems that shear stress could favor adhesion of CD34+ cells to endothelial cells.

Antigens, CD34↗
PubMed2002

[Granulocyte sarcoma of the pancreas without extra-pancreatic location].

INTRODUCTION: Granulocyte sarcoma (GS), also known as chloroma, is a localized malignant tumor composed of myeloid cells, the diagnosis of which is difficult. The pancreatic location and recurrence, aside from any context of malignant hemopathy, are exceptional. OBSERVATION: A 31-year-old woman developed an isolated and recurrent granulocyte sarcoma of the pancreas, without any context of a malignant hemopathy. The diagnosis retained on extemporaneous examination was an adenocarcinoma of the pancreas, because of the non-specific necrotic nature of the tumor. The immuno-histochemical exploration corrected the diagnosis. Despite local surgery, an isolated tumor recurred 6 months later. This relapse was treated with radiotherapy followed by heavy chemotherapy, identical to that applied in acute myeloblastic leukemia (AML). Ten months later, remission was stable and complete. COMMENTS: Isolated granulocyte sarcomas located in the pancreas are exceptional and have often led to initial erroneous diagnosis. Immuno-histochemical methods are essential in order to obtain correct diagnosis. Despite the localized nature of the tumor, intensive AML-type chemotherapy is necessary.

Adenocarcinoma↗
PubMed2001

Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients.

To comparatively assess first-line treatment with fludarabine and 2 anthracycline-containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone) and ChOP (cyclophosphamide, vincristine, prednisone plus doxorubicin), in advanced stages of chronic lymphocytic leukemia (CLL), previously untreated patients with stage B or C CLL were randomly allocated to receive 6 monthly courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet stages. End points were overall survival, treatment response, and tolerance. From June 1, 1990 to April 15, 1998, 938 patients (651 stage B and 287 stage C) were randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall remission rates (58.2%; ChOP, 71.5%; FAMP; 71.1%; P <.0001 for each), including lower clinical remission rates (CAP, 15.2%; ChOP, 29.6%; FAMP, 40.1%; P =.003). By contrast, median survival time did not differ significantly according to randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups, respectively). Incidences of infections (< 5%) and autoimmune hemolytic anemia (< 2%) during the 6 courses were similar in the randomized groups, whereas fludarabine induced, compared to ChOP and CAP, more frequent protracted thrombocytopenia (P =.003) and less frequent nausea-vomiting (P =.003) and hair loss (P <.0001). For patients with stage B and C CLL first-line fludarabine and ChOP regimens both provided similar overall survival and close response rates, and better results than CAP. However, there was an increase in clinical remission rate and a trend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL.

Aged↗
PubMed2001

Long-term results of venous revascularization for Paget-Schroetter syndrome in athletes.

The indications for surgical management of primary subclavian vein thrombosis are not agreed upon. This report describes our experience in the treatment of exertional thrombosis causing Paget-Schroetter syndrome in 10 athletes between 18 and 45 years of age. In seven patients urokinase was injected and this resulted in complete revascularization in three cases (42.9%). The remaining three patients were treated by anticoagulation using heparin with adjuvant Coumadin after resolution of thrombosis. Duplex ultrasonography and dynamic phlebography were performed to assess the results of drug treatment. Decompression of the thoracic outlet was performed secondarily using various techniques, including first-rib resection in 10 cases, scalenectomy in 9, and resection of a clavicular callus in 1 case. In six patients, persistent debilitating venous stasis required revascularization by axillojugular bypass in three cases, thrombectomy in two, and axillojugular anastomosis in one case. All patients were reexamined. Mean follow-up was 45 months. Symptomatic relief and vein patency was achieved in all cases. All patients were able to resume sports activity. In agreement with previous studies, our findings confirm the efficacy of immediate anticoagulation, thrombolysis, and complete decompression of the thoracic outlet. Should this approach fail to reestablish patency, axillosubclavian vein revascularization can provide good mid-term results.

Adolescent↗
PubMed2001

Spontaneous dissection of the celiac artery.

Spontaneous dissection of the celiac artery (CA) is uncommon, considering the number of isolated lesions without associated aortic dissection and exclusive of abdominal trauma. We have treated five cases of isolated spontaneous dissection of the CA or its branches. There were three men and two women with a mean age of 54 years. The presenting manifestation was acute epigastralgia in three cases and chronic abdominal pain in one. In the remaining case, dissecting CA was a coincidental finding. All patients underwent abdominal Doppler ultrasound and CT scan imaging, which demonstrated aneurysm in three cases and dissection in two. Work-up also included arteriography in three cases and magnetic resonance (MR) angiography in one. Management consisted of emergency surgical repair in three cases and close surveillance in two. The repair procedure was resection-anastomosis in one case and prosthetic bypass to the hepatic artery in two cases. Postoperative recovery was uneventful in all three cases and patients were symptom-free at 6, 8, and 18 months. Both patients under surveillance were symptom-free at 1 and 2 years. Because of the risk of ischemic and hemorrhagic complications, surgery should be considered for any patient with CA dissection. However, some patients with uncomplicated asymptomatic lesions may be eligible for medical treatment with regular surveillance.

Adult↗
PubMed2001

[Hepatic artery aneurysms].

AIM OF THE STUDY: The aim of this retrospective study was to report a series of nine aneurysms of the hepatic arteries, including real aneurysms (n = 4), pseudoaneurysms (n = 3) and false aneurysms (n = 2) observed from 1987 to 1999. PATIENTS: There were 7 men and 2 women (mean age: 58 years). In 3 cases, the aneurysm was asymptomatic and detected by sonography; in 4 cases it was revealed by rupture with a severe hemorrhage and in 2 cases by cholestasis. The aneurysm was located on right (n = 3), proper and common (n = 3), proper (n = 2), and common (n = 1) hepatic arteries. The aneurysm was associated with hepatocellular carcinoma (n = 1), carcinoma of the head of the pancreas (n = 1) and liver metastases (n = 1). METHODS AND RESULTS: Eight patients were operated and one of them was operated three times. Hepatic arterial blood supply was restored in 6 patients with simple suture (n = 1), Goretex graft (n = 2), allograft (n = 2) and autologous vein (n = 1), with one failure which required liver retransplantation. Only one of the three attempts of embolization was successful. One patient with surgical contraindications died from hemobilia after embolization failure. During follow-up, there was one thrombosis of the common hepatic artery which had been excluded and two late deaths: one from rupture of a false aneurysm after bypass with an allograft and one by terminal progression of the cancer. The other 6 patients were alive at the time of this study. CONCLUSION: Clinical characteristics and therapeutic indications of hepatic arterial aneurysm are variable. Management is usually surgical, while embolization is reserved for special circumstances. Restoration of the hepatic arterial blood supply is necessary in aneurysms located on the proper hepatic artery.

Adult↗
PubMed2001

[Quantitative expression of the adhesion receptors VLA-4, VLA-5, L-selectin, MAC-1, and ICAM-1 on the surface of CD34+ cells].

The aim of this work was to quantify by flow cytometry the main adhesion receptors on CD34+ cells. These cells were isolated from bone marrow (BM) or mobilized peripheral blood (PB). The proportions of CD34+/CD49d+ and CD34+/CD49e+ are weaker on PB cells, without quantitative expression variation. This phenotypic variation may induce CD34+ cells exist from BM into circulation, promoting the mobilization. The homing to the BM implicate the CD62L receptor, which expression was found more frequently and stronger on PB cells than on BM. The CD11b, CD18 and CD54 receptors are implicated in CD34+ cells adhesion to BM micro-environment. No significant variation in CD34+/CD11b+ and CD34+/CD18+ cells frequency was noted. Moreover, CD54 receptor was more frequently expressed on PB cells. Quantitative analysis revealed that CD18 was more strongly expressed on BM than on PB cells. This quantitative variation could promote progenitor adhesion by interacting with stromal cells. Finally, quantitative expression of the main receptors on CD34+ cells provides an original option for studying CD34+ cells during the mobilization, the homing or the adhesion to BM micro-environment.

Antigens, CD↗