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P Morel

Publications and source records attributed to P Morel.

At least 109 records · Page 6Linked to original sources

Successful treatment in two cases of steroid-dependent cutaneous polyarteritis nodosa with low-dose methotrexate.

To the best of our knowledge, only 3 cases of cutaneous polyarteritis nodosa (PAN) treated successfully with methotrexate (MTX) have been reported in the medical literature. We report 2 further cases of steroid-dependent cutaneous PAN treated successfully with low-dose weekly MTX therapy. The clinical and biological tolerance of MTX was excellent. The cutaneous lesions started to regress within 3 weeks. One of the patients reported full recovery which lasted 2 years after stopping the therapy. So, MTX seems to be an interesting therapy in the treatment of PAN because of its relatively low toxicity, its simple use, its quick action and prolonged results after MTX has been stopped.

Adrenal Cortex Hormones↗

Ig-binding receptors on human NK cells as effector and regulatory surface molecules.

The receptors on human natural killer 9NK cells which can specifically bind the Fc portion of immunoglobulin molecules (Fc receptors) have been extensively studied. The best known and studied Fc receptor on human NK cells is FcgammaRIIIa. Interactions of NK cells with IgG antibodies via this receptor are well known to induce a signal transduction cascade and lead to antibody-dependent cell-mediated cytotoxicity (ADCC) as well as release of various cytokines. In addition, interactions with monomeric IgG and FcgammaRIIIa have been demonstrated, which result in negative regulation of NK activity and other immunomodulatory effects. Over the past several years, it has also become increasingly appreciated that human NK cells express a variety of other Fc receptors, including FcmuR, which also can mediate effector and immunoregulatory functions. Also, a novel form of FcgammaR has been demonstrated on human NK cells, termed FcgammaRIIc. Recent molecular studies have shown considerable polymorphism in the genes for FcgammaIIc and the functional consequences are being dissected. This appears to include cross-talk between FcgammaRIIIa and at least some forms of FcgammaRIIc, which may have important functional consequences.

Animals↗

[Black tumor].

Explore the source record for details and available documents.

Adult↗

Alloimmunization and erythrocyte autoimmunization in transfusion-dependent thalassemia patients of predominantly asian descent.

The development of hemolytic alloantibodies and erythrocyte autoantibodies complicates transfusion therapy in thalassemia patients. The frequency, causes, and prevention of this phenomena among 64 transfused thalassemia patients (75% Asian) were evaluated. The effect of red blood cell (RBC) phenotypic differences between donors (mostly white) and Asian recipients on the frequency of alloimmunization was determined. Additional transfusion and patient immune factors were examined. 14 (22%) of 64 patients (75% Asian) became alloimmunized. A mismatched RBC phenotype between the white population, comprising the majority of the donor pool, and that of the Asian recipients, was found for K, c, S, and Fyb antigens, which accounts for 38% of the alloantibodies among Asian patients. Patients who had a splenectomy had a higher rate of alloimmunization than patients who did not have a splenectomy (36% vs 12.8%; P =.06). Erythrocyte autoantibodies, as determined by a positive Coombs test, developed in 25% or 16 of the 64 patients, thereby causing severe hemolytic anemia in 3 of 16 patients. Of these 16, 11 antibodies were typed immunoglobulin G [IgG], and 5 were typed IgM. Autoimmunization was associated with alloimmunization and with the absence of spleen (44% and 56%, respectively). Transfused RBCs had abnormal deformability profiles, more prominent in the patients without a spleen, which possibly stimulated antibody production. Transfusion of phenotypically matched blood for the Rh and Kell (leukodepleted in 92%) systems compared to blood phenotypically matched for the standard ABO-D system (leukodepleted in 60%) proved to be effective in preventing alloimmunization (2.8% vs 33%; P =.0005). Alloimmunization and autoimmunization are common, serious complications in Asian thalassemia patients, who are affected by donor-recipient RBC antigen mismatch and immunological factors.

Adolescent↗

Prognostic significance of survivin expression in diffuse large B-cell lymphomas.

Survivin is an inhibitor of apoptosis overexpressed in various human cancers but undetectable in normal differentiated tissues. A potential expression and prognostic significance of survivin was studied in 222 patients with diffuse large B-cell lymphomas (centroblastic, 96%; immunoblastic, 4%). All patients were enrolled between 1987 and 1993 (median follow-up, 7 years) in the LNH87 protocol of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA) and treated either with the reference ACVBP arm (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone)[AU3A] (n = 79) or other experimental anthracycline-containing regimens (n = 143). The characteristics of these patients were median age of 56 years; serum lactate dehydrogenase (LDH) greater than 1N, 60%; stage III-IV, 55%; performance status, according to the Eastern Cooperative Oncology Group (ECOG) scale, more than 1, 23%; extranodal sites more than 1, 29%; mass more than 10 cm, 44%; bone marrow involvement, 15%. Of the 222 patients studied, 134 (60%) revealed survivin expression in virtually all tumor cells by immunohistochemistry. The overall 5-year survival rate was significantly lower in patients with survivin expression than in those without (40% vs 54%, P =.02). Multivariate analysis incorporating prognostic factors from the International Prognostic Index (IPI) identified survivin expression as an independent predictive parameter on survival (P =.03, relative risk [RR] = 1.6) in addition to LDH (P =.02, RR = 1.6), stage (P =.03, RR = 1.7), and ECOG scale (P =.05, RR = 1.6). A second analysis incorporating IPI as a unique parameter demonstrated that survivin expression (P =.02, RR = 1.6) remained a prognostic factor for survival independently of IPI (P =.001, RR = 1.5). Survivin expression may be considered a new unfavorable prognostic factor of diffuse large B-cell lymphoma. (Blood. 2000;96:1921-1925)

Adolescent↗

[Start of an adult living donor liver transplantation program in Switzerland].

The shortage of cadaver organs has prompted transplant centres to seek new sources of grafts. While living-donor left lobe transplantation (segments II and III) is an established procedure for children, living donor right liver transplantation (segments V, VI, VII, VIII), which can provide adequate liver mass for an average-sized adult patient, is technically more demanding and potentially associated with higher risks for the donor. In view of the permanent shortage of organs in Switzerland, we started an adult living donor liver transplantation programme in 1999 with the approval of the Clinical Ethics Committee of Geneva University Hospitals. Donor evaluation was performed only after the recipient had been officially registered for transplantation in the national waiting list. Preoperative evaluation consisted of a preliminary information phase with blood tests and Doppler ultrasonography, a second phase with radiological non invasive investigations (CT scan with volume measurements, magnetic resonance cholangiography) and a third phase including liver biopsy and angiography. A formal psychiatric evaluation was performed in all cases and detailed consent was required. Eight potential donors were investigated, 5 were not retained because of too small right liver or steatosis, and 3 were accepted (wife, son, sister). Living-donor hepatectomy was performed without interrupting the vascular blood flow. The liver graft was perfused ex-situ with University of Wisconsin solution. The grafts were anastomosed to the preserved vena cava of the recipient and the portal and arterial anastomoses were performed without interposition grafts, with short cold ischaemic times in the 3 cases. The graft-to-recipient weight ratio ranged from 1.04 to 1.12%. The grafts worked immediately; the post-operative course in the 3 recipients was unremarkable and no rejection episode occurred. Significant complications were observed in one donor (percutaneously drained bilioma and spontaneously resolved popliteal sensory palsy). Living-donor right liver transplantation is a potentially valuable solution to the increasing shortage of donor organs. The procedure can be performed safely provided stringent criteria for donor selection, for donor-recipient coupling (> 1% graft to body weight ratio) and for centre selection (experience in liver surgery, reduced and split liver transplantation) are applied.

Adenosine↗

patients with the description of a new scoring system and its validation on 253 other patients.

Using Cox models, we established a new prognostic system based on simple clinical parameters in a training series of 232 patients whose diagnoses were made before 1989. Adverse prognostic factors for survival (P <.01) were age 65 years or older, male gender, albumin level lower than 40 g/L, hemoglobin level lower than 12 g/dL, platelet count less than 150 x 10(9)/L, white blood cell count less than 4 x 10(9)/L, high number of cytopenias, and hepatomegaly. Taking age (age 65 years or older, 1 point; younger than 65 years, 0 points), albumin (less than 40 g/L, 1 point; 40 g/L or more, 0 points), and total number of cytopenias (no cytopenia, 0 points; 1 cytopenia, 1 point; 2 or 3 cytopenias, 2 points) into account, we separated the 232 patients into 3 groups with low (score 0 or 1), intermediate (score 2), or high (score 3 or 4) risk, associated with 5-year survival rates at 87%, 62%, and 25%, respectively (P <.0001). Only the presence of 2 or 3 cytopenias was an independent prognostic factor among patients younger than 65 years (P <.0001). Albumin level lower than 40 g/L and the presence of 1 or more cytopenia defined a prognostic system for patients 65 years and older. Patients at low risk, intermediate risk, and high risk had 5-year survival rates at 92%, 63%, and 27%, respectively (P <.0001). The 3 prognostic systems separated the 167 patients of a test series in groups with significantly different survival rates. The overall scoring system retained a significant prognostic value in 86 additional patients treated between 1990 and 1996. We conclude that the combination of age, albumin level, and blood cell counts might help to select patients with Waldenström macroglobulinemia for treatment and to evaluate therapeutic results.

Adult↗

Quality of life-adjusted survival analysis of high-dose therapy with autologous bone marrow transplantation versus sequential chemotherapy for patients with aggressive lymphoma in first complete remission. Groupe d'Etude les Lymphomes de l'Adulte (GELA).

Evaluating high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in term of both duration and quality of life (QOL) presents major interests for patients with non-Hodgkin lymphoma. The quality-adjusted time without symptom and toxicity (Q-TWiST) methodology was applied to the LNH87-2 trial comparing HDT with ASCT versus sequential chemotherapy in 541 patients in first complete remission (CR). Overall survival (OS) and disease-free survival (DFS) curves were used to estimate duration of 4 health states: acute short-term toxicity (Tox1), secondary toxicity (Tox2), time without symptom and toxicity (TWiST), and relapse (Rel). Areas under survival curves (AUC) were retrospectively weighted according to QOL coefficients. HDT increased, but not significantly, TWiST (+2. 4 months in AUC, P =.17) and decreased Rel (-3 months, P <.01). Survival estimates did not differ between the 2 treatments (AUC 47.7 months for OS, 39.7 months for DFS). High-risk patients treated by HDT versus chemotherapy had a significant benefit in DFS (AUC 28.8 versus 24.9 months, P <.01) but not in OS (AUC 37.3 versus 36 months, P =.27). Sensitivity analysis, performed by varying QOL coefficients, demonstrated significant quality-adjusted survival gain in high-risk patients treated by HDT. In low-risk patients, a diagram provided an aid to clinical decision-making. This analysis supports the use of HDT in these patients with adverse prognostic factors in the first CR, even after adjusting for QOL using the Q-TWiST method. (Blood. 2000;95:3687-3692)

Adult↗

Human islet transplantation: lessons from 13 autologous and 13 allogeneic transplantations.

BACKGROUND: A series of 13 islet autotransplantations and 13 islet allotransplantations performed between 1992 and 1999 at the University Hospital of Geneva are presented. Factors affecting the outcome are analyzed. METHODS: Islet autotransplantation has been performed in seven patients with chronic pancreatitis and in six patients with benign tumors undergoing extensive pancreatectomy. Islet allografts were performed in C-peptide-negative patients simultaneously or after a kidney or lung transplantation. Each recipient received islets from one to four donors. Panel-reactive antibodies were monitored by microlymphocytotoxicity test. RESULTS: Eleven of 13 patients who underwent autotransplantation maintained insulin independence for 6 months to 5 years. Two years after autologous islet transplantation, five of nine patients were insulin independent with an glycosylated hemoglobin of 5.9%. Three late islet failures occurred in patients with chronic pancreatitis. Islet yield was significantly lower in patients with chronic pancreatitis than in patients with benign tumors (2044 equivalent islet number/gram resected pancreas versus 5184 equivalent islet number/gram; P=0.037). In islet allotransplantation, no early graft loss was found. All 13 patients who underwent allotransplantation had basal C-peptide levels above 0.3 nmol/L for 3 months to 5 years. Mean glycosylated hemoglobin decreased from 9.1% before transplantation to 5.5% at month 3. Insulin independence was achieved in two type I diabetic patients. In four of six patients with graft failure, the graft had induced panel-reactive antibodies. CONCLUSIONS: In islet autotransplantation, the reduced number of islets that can be isolated from fibrotic pancreata may be the major limiting factor. In islet allotransplantation, early graft function can now be consistently achieved. Islet allografts seem to be highly immunogenic, and chronic islet failure cannot be prevented consistently by conventional immunosuppression.

Autoimmunity↗

Long-term metabolic results after pancreatic resection for severe chronic pancreatitis.

HYPOTHESIS: Type and extent of pancreatic resection have little effect on long-term development of diabetes in patients with chronic pancreatitis (CP) considering the distinctive relentless progression of the disease. DESIGN: A case series of consecutive patients included over a 10-year period. Median duration of follow-up was 6.3 years. Follow-up of survivors was at least 5 years (median, 7.7 years). SETTING: A referral center in a university hospital. PATIENTS: All 68 patients (57 men and 11 women) who underwent pancreatic resection for CP during the study period were included. Median age of patients was 44 years. Complete follow-up was obtained for all patients. INTERVENTIONS: Resection procedures included 35 proximal pancreatoduodenectomies (51%), 31 distal pancreatectomies (46%), and 2 total pancreatoduodenectomies (3%). Four patients (6%) received autologous intraportal islet transplants. MAIN OUTCOME MEASURES: Time from surgery to introduction of insulin therapy or death, perioperative morbidity and mortality, and pain control. RESULTS: Fifty-one patients (75%) had experienced acute episodes of CP 5 months to 13 years before resection. Perioperative mortality and morbidity were 1.5% and 21.0%, respectively. Satisfactory long-term pain control was achieved in 61 patients (90%). Actuarial survival was 54% at 10 years and was significantly worse for patients with alcoholic CP (48% vs 78%; P =.04). Diabetes-free survival was 26% at 10 years, with no difference according to type or extent of pancreatic resection. CONCLUSIONS: Pancreatic resection for severe CP is safe and has good long-term results on pain control but is performed late in the course of disease. Earlier resection and islet of Langerhans autotransplantation should be considered for patients who are inexorably heading toward diabetes, regardless of type and extent of resection performed.

Adult↗

Reversible immortalization of human primary cells by lentivector-mediated transfer of specific genes.

We exploited the ability of lentiviral vectors to govern the stable transduction of cells irrespective of their cycling status to induce the reversible immortalization of human primary cells. First, bicistronic HIV-derived lentiviral vectors expressing GFP- and the HSV1 thymidine kinase and containing the LoxP sequence in their LTR (HLox) were used to transduce HeLa cells. Cre expression led to efficient proviral deletion, and unexcised cells could be eliminated by ganciclovir treatment. A human liver biopsy was then exposed to a combination of HLox vectors that harbored either the SV40 large T (TAg) or the human telomerase (hTERT) DNAs in place of GFP. This led to the isolation of liver sinusoidal endothelial cell (LSEC) clones that exhibited an immortalized phenotype while retaining most of the features of primary hLSEC. Complete growth arrest of these cells was observed in 2 days of Cre expression, and the resulting stationary culture could be kept for at least 2 weeks. Transduction of human adult pancreatic islets with HLox vectors coding for Tag and Bmi-1 also induced the proliferation of insulin-positive cells. These results indicate that lentivectors can be used to mediate the reversible immortalization of primary nondividing cells and should allow for the production of large supplies of a wide variety of human cells for both therapeutic and research purposes.

Animals↗

Acute left colonic diverticulitis--compared performance of computed tomography and water-soluble contrast enema: prospective evaluation of 420 patients.

PURPOSE: The most valuable radiologic examination to be done initially when acute left colonic diverticulitis is suspected is still a matter of controversy. This study compares the performance between water-soluble contrast enema and computed tomography. METHODS: From 1986 to 1997, all patients admitted in our emergency center with clinically suspected left-colonic diverticulitis had a contrast enema and a computed tomography within 72 hours of their admission, unless clinical findings required immediate laparotomy. They were prospectively included in the study if one or both radiologic examinations showed signs of acute diverticulitis or diverticulitis was surgically removed and histologically proven or both. Diverticulitis was considered moderate when computed tomography showed localized thickening of the colonic wall (5 mm or more) and inflammation of pericolic fat and contrast enema showed segmental lumen narrowing and tethered mucosa; it was considered severe when abscess or extraluminal air or contrast or all three were observed on computed tomography and when one or both of the last two signs were seen on contrast enema. Of 542 patients, 420 who had both computed tomography and contrast enema entered the study. RESULTS: The performance of computed tomography was significantly superior to contrast enema in terms of sensitivity (98 vs. 92 percent; P = 0.01), which was calculated from patients who had their colon removed and whose diverticulitis was histologically proven, and in the evaluation of the severity of the inflammation (26 vs. 9 percent; P = 0.02). Moreover, of 69 patients who had an associated abscess seen on computed tomography, only 20 (29 percent) had indirect signs of this complication on contrast enema. CONCLUSIONS: In the diagnostic evaluation of acute left-colonic diverticulitis, computed tomography should be preferred to contrast enema as the initial radiologic examination because of its statistically significant superiority in sensitivity and for its significantly better performance in the detection of severe infection, especially when an abscess is associated with the disease.

Abscess↗

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↗

Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator.

BACKGROUND: Multimodal therapy is used increasingly in advanced gastrointestinal tumors. Potential benefits of using an intraoperative adjuvant therapy during laparoscopy for cancer have been documented in animal studies. The aim of this study was to develop a device that could deliver such an intraoperative drug therapy. METHODS: We developed a micropump suitable for minimally invasive surgery procedures that allowed microdroplets of therapeutic substance to be distributed into the pneumoperitoneum (CO2), creating a "therapeutic pneumoperitoneum." A closed-loop control system regulates drug delivery according to the gas flow. In vitro, the micropump is able to aerosolize various aqueous and ethanol solutions, including cytostatic and bacteriostatic drugs and adhesion-modulating agents. The size of the microdroplets has been optimized to prevent visual artifacts. RESULTS: The micropump was tested in an animal model (pig). The system was inserted into a 5-mm trocar. After insufflation of a 12-mm CO2 pneumoperitoneum, laparoscopic sigmoid colon resections could be performed with no special difficulties. No fog developed, and no system-related complication was observed. At autopsy, the active principle was distributed to all exposed peritoneal surfaces. CONCLUSIONS: As opposed to conventional peritoneal washing, therapeutic pneumoperitoneum reaches the entire peritoneal surface, allowing an optimal drug distribution. Drug diffusion into the tissues is enhanced by the intraperitoneal pressure. Precise determination of the instantaneous and total drug quantity is possible. Therefore, this drug delivery system has several advantages over conventional irrigation. Its potential domains of application are locoregional cancer therapy, prevention of port-site recurrences, immunomodulation, analgesia, peritonitis, and prevention of postoperative adhesions.

Abdominal Neoplasms↗

Recurrent cholestatic jaundice associated with generalized pustular psoriasis: evidence for a neutrophilic cholangitis.

Generalized pustular psoriasis can result in systemic complications. We report the case of a woman with relapsing generalized pustular psoriasis and recurring episodes of cholestatic jaundice. Liver biopsy performed during an attack showed a neutrophilic infiltrate surrounding and invading portal triad bile ducts. Ultrasonographic exams and retrograde cholangiography ruled out biliary tract disease. This observation suggests that recurring cholestatic jaundice in pustular psoriasis is related to a neutrophilic cholangitis.

Adult↗