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Biomedical subjects

P Morel

Publications and source records attributed to P Morel.

At least 145 records · Page 8Linked to original sources

Autologous bone marrow transplantation for recurrent malignant lymphoma after liver transplantation.

BACKGROUND: Cancer chemotherapy in chronic carriers of hepatitis B virus is known to promote viral replication, and, when immunosuppressive treatment is stopped, the return of immune competence can be followed by a fulminant hepatitis. Liver transplantation may be required and has been successfully performed for this condition. However, malignancy recurrence after transplantation has not been reported yet. METHODS AND RESULTS: We here report the case of an asymptomatic hepatitis B surface antigen carrier who developed a malignant lymphoma, which was treated by chemotherapy. After cessation of chemotherapy, he developed a fulminant hepatitis, requiring liver transplantation. Three years later, he developed a recurrent malignant lymphoma, which was treated successfully by autologous bone marrow transplantation. In order to prevent viral replication, lamivudine and intermittent administration of fresh-frozen plasma highly concentrated in anti-HBs immunoglobulin was initiated before the bone marrow transplantation. The patient remains well 12 and 56 months after autologous bone marrow and liver transplantation, respectively. CONCLUSIONS: This experience suggests that all hepatitis B surface antigen-positive patients for whom chemotherapy is indicated would benefit from prophylactic antiviral hepatitis B virus therapy. Furthermore, successful autologous bone marrow transplantation is possible after liver transplantation.

Bone Marrow Transplantation↗

Traumatic neuroma with biliary duct obstruction after orthotopic liver transplantation.

BACKGROUND: Traumatic neuromas may develop after injury to nerve fibers encased in Schwann cells. The incidence of symptomatic neural tumors appears to be low after orthotopic liver transplantation (OLT). Only two cases of biliary stricture caused by infiltrating traumatic neuroma have been described previously. METHODS: We report two new cases of biliary tract obstruction after OLT that failed to respond to percutaneous balloon dilatation and were corrected by a resection of the bile duct stricture followed by biliary reconstruction with a Roux-en-Y jejunal loop. RESULTS: The first patient (17 months after OLT) had a traumatic neuroma appearing as a distinct mass with nerve bundles confirmed histologically; the traumatic neuroma in the second patient (5 months after OLT) was a nerve stump with infiltration of nervous elements in the bile duct. Both patients recovered without complications. CONCLUSIONS: Traumatic neuromas should be considered in the differential diagnosis of late biliary stricture after OLT, in particular when not responding to percutaneous dilatation or stenting.

Anastomosis, Roux-en-Y↗

Leg ulcers and hydroxyurea: forty-one cases.

BACKGROUND: Hydroxyurea is an antitumor agent used to treat chronic myeloproliferative disorders. Leg ulcerations have been reported in patients undergoing long-term hydroxyurea therapy for myeloproliferative diseases. To better define this dermatological adverse effect of hydroxyurea therapy and to try to understand the pathophysiological process of this disease, we collected medical information for such patients in a multicenter retrospective study. OBSERVATIONS: Forty-one patients (mean age, 67 years) developed leg ulcerations while undergoing hydroxyurea therapy (mean therapy duration, 5 years). The sex ratio was 1, and there was no underlying vascular disease. Hematologic abnormalities were identified. Complete recovery from the ulcerations occurred quickly after withdrawal of treatment in 33 (80%) of the cases. CONCLUSIONS: This longest-reported series of patients confirms the role of hydroxyurea therapy in the onset of leg ulcerations. Healing or improvement requires cessation of treatment. Cutaneous atrophy and impaired wound healing may explain the relationship between hydroxyurea and leg ulcers. In addition, the megaloblastic erythrocytes resulting from the presence of hydroxyurea may circulate poorly through the capillary network. A prospective study in hematologic centers would be valuable.

Adult↗

Low dose T-cell lymphocyte infusion combined with marrow T-cell depletion as prophylaxis of acute graft vs host disease for HLA identical sibling bone marrow transplantation.

T-cell depletion (TCD) of the bone marrow graft remains the most effective method to prevent severe graft versus host disease after allogeneic bone marrow transplantation. Early studies of HLA-identical sibling transplants showed that although T-cell depletion decreased GVHD, T-cell depleted transplants had higher risks of graft failure and leukemia relapse, leukemia free survival (LFS) was not improved compared to non-T-cell depleted transplants. In order to avoid graft failure and increased risk of relapse associated with this approach, we initiated a pilot study of T-cell depletion of the marrow graft combined with reinfusion of a fixed quantity of CD2+ peripheral blood T-cells. Depletion technique consisted in negative purging using CD2 and CD7 monoclonal antibodies (MoAbs) followed by rabbit complement cytolysis. This approach was associated with an intensified conditioning regimen using total body irradiation, high-dose cytosine arabinoside and melphalan (TAM) for all but one patient. Twenty-one patients were included with a mean age of 40 years. Only one acute severe Graft Versus Host Disease (GVHD) was observed and all patients engrafted. At 63 months, probability of survival is 42.86% with a relapse risk of 19.89%, two patients died from B-cell lymphoproliferative disease, seven other died from the procedure partially because of the use of the TAM as pretransplant regimen. This approach is being pursued by a gene therapy trial using herpes-simplex - 1 thymidine kinase gene expressing peripheral donor T-cells.

Adult↗

Improvement of the effect of hepatocyte isograft in the Gunn rat by cotransplantation of islets of Langerhans.

PURPOSE: Hepatocyte transplantation (HcTX) has been investigated for many years as an alternative therapy to orthotopic liver transplantation to treat hepatic congenital enzymatic deficiency disease. The animal model most used is the Gunn rat, which presents a hyperbilirubinemia caused by the lack of uridine-diphosphate-glucuronyl-transferase. Some investigators have clearly described a hepatotrophic effect mediated by islets of Langerhans (IL) when transplanted with hepatocytes (Hc). In this study, the functional effect of cotransplanted IL on hepatocytes (co-HcTX) in Gunn rats in an isograft model is assessed. METHODS: Two groups are compared: group 1 (n = 6), HcTX to group 2 (n = 6), co-HcTX. Cells isolated by enzymatic digestion are transplanted directly into the splenic parenchyma. Blood samples are taken regularly until day 100 to measure the unconjugated bilirubin (UB). Histological examination of the spleen is performed at the end of the experiment. RESULTS: Both groups show a significant decrease of the UB: group 1, 47%; group 2, 65%. The decrease is statistically more pronounced with co-HcTX. The histological analysis shows a trophic effect of the IL on the grafted hepatocytes in the co-HcTX group. CONCLUSIONS: The HcTX and the co-HcTX correct partially the hyperbilirubinemia of the Gunn rat. A functional assessment has been performed to evaluate the effect of cotransplanted IL on HcTX.

Analysis of Variance↗

Meropenem (1.5 g/day) is as effective as imipenem/cilastatin (2 g/day) for the treatment of moderately severe intra-abdominal infections.

This multicentre, open-label, randomised trial compared meropenem (0.5 g/8 h) and imipenem/cilastatin (at the commonly used dosage of 0.5 g/6 h) in monotherapy in patients with moderately severe intra-abdominal infections (IAIs). In total, 161 patients were randomised (82 meropenem, 79 imipenem/cilastatin). The mean APACHE II scores in the two groups were 5.8 and 6.4, respectively. At the end of therapy, 65/71 (91.6%) evaluable meropenem recipients were clinically cured or improved, compared to 60/64 (93.8%) imipenem/cilastatin recipients. This difference and that in an intention-to-treat analysis (82.1 vs 86.1%, respectively), were not statistically significant. Both drugs were generally well tolerated. Thus, meropenem 0.5 g/8 h is as clinically effective and well tolerated as imipenem/cilastatin 0.5 g/6 h in moderately severe IAIs.

APACHE↗

Successful treatment of a pseudoaneurysm of the cystic artery with microcoil embolization.

Pseudoaneurysms of visceral arteries are uncommon but well-characterized vascular abnormalities, usually provoked by intraabdominal inflammatory processes such as pancreatitis or cholecystitis, or by surgical trauma. However, pseudoaneurysms of the cystic artery are rare. They complicate cholecystitis or cholecystectomy, and manifest as hemobilia as they rupture into the biliary tree. The advent of transcatheter embolization techniques has begun to allow minimally invasive treatment of these life-threatening complications. Transcatheter embolization can be performed using several types of material, such as synthetic occlusive emulsions, gelatin sponges or other particles, or metallic microcoils. Microcoils are small metallic helical particles, made of stainless-steel, platinum, or tungsten. Super-selective catheterization of an artery and release of microcoils causes the vessel to thrombose and allows control of bleeding.

Adult↗

[Primary surgical care of pelvic fractures associated with perineal laceration].

Unstable fractures of the pelvic ring, associated to perineal lacerations are severe injuries occurring during high-energy trauma. High rates of septic complications and mortality have been reported with these injuries. Current treatment guidelines, while dealing with open pelvic fractures or dislocations are discussed, based on a current review of the literature and on our local experience. At our institution, 55 unstable type B or C fractures of the pelvic ring were treated by osteosynthesis between 1991 and 1997. Of these, 11 patients presented with an associated perineal laceration (20%). Simultaneously to the immediate pelvic ring fixation, a diversion colostomy was performed in all these patients. Repeated wound debridements and wide spectrum antibioprophylaxis were associated. Of these 11 patients presenting an open pelvic fracture, only one died of pelvic sepsis at three weeks. 10 patients survived (91%) and went on to bony union, without any local infectious complications. Aggressive multidisciplinary initial surgical management is a rule when dealing with this type of injuries, immediate colostomy and careful wound debridement must be associated to the initial osteosynthesis.

Adult↗

Management of focal nodular hyperplasia and hepatocellular adenoma.

Hepatocellular adenoma and focal nodular hyperplasia are two benign hepatic tumors which are mainly detected in healthy young women. Hepatocellular adenoma is an indication for surgery due to the risk of haemorrhage and malignant transformation. By contrast, focal nodular hyperplasia should be managed conservatively. However, precise diagnosis of these benign liver tumors remains difficult and sometimes impossible, despite new imaging techniques. Because of the risk of diagnostic error, resection or large biopsies of presumed liver tumors should be performed in young women (and a fortiori in men and older patients in whom focal nodular hyperplasia is less prevalent) when the diagnosis of focal nodular hyperplasia is not firmly established. The risk of liver surgery in young patients with normal liver parenchyma is, in the opinion of the authors, lower than the risk of a mistaken diagnosis.

Adenoma, Liver Cell↗

The VIM3-AraC regimen followed by autologous stem cell transplantation in refractory or relapsing aggressive non-Hodgkin's lymphoma. A prospective study of 71 consecutive cases.

We evaluated with an intent-to-treat analysis the response rate, the disease-free survival (DFS), and the overall survival after a multidrug salvage regimen (VIM3ARAC), followed by stem-cell transplantation (SCT) in case of response, in patients with aggressive non-Hodgkin's lymphoma (NHL) who progressed on or after the first-line therapy. Seventy-one patients (refractory: 15; relapse 'on therapy': 36; and relapse 'off therapy': 20) received two courses of VIM3ARAC (teniposide, ifosfamide, mitoxantrone, mitoguazone, high-dose methotrexate, high-dose cytarabine, prednisolone). SCT was performed only in patients with minimal disease after the second course. The response rate was 72%. It was not influenced by response to first-line therapy. Forty-eight patients (68%), including 32 complete responders, fulfilled response criteria for SCT. Thirty-six patients underwent SCT (allogeneic: 3; autologous: 33). The 4-year DFS rate of the 48 responding patients was 39%. The actuarial survival at 4 years was 34% for all patients. Relapse off therapy and a performance status <2 at relapse were the only two independent favorable prognostic factors for survival. In conclusion, VIM3AraC is associated with a high response rate in relapsing and refractory aggressive NHL. Up to half of the patients could receive SCT. This chemotherapy, followed by SCT could durably salvage 34% of these patients.

Adolescent↗

No evidence for a role of human herpesvirus type 8 in sarcoidosis: molecular and serological analysis.

The aim of this study was to analyse the association between human herpesvirus type 8 (HHV8) and sarcoidosis. Using nested polymerase chain reaction (PCR), we tested the presence of HHV8 DNA sequences in 13 skin specimens and peripheral blood mononuclear cells from eight patients suffering from sarcoidosis. We also looked for the presence of HHV8 antibodies in the sera of 28 patients with sarcoidosis using three techniques: two indirect immunofluorescence assays and an enzyme-linked immunosorbent assay with recombinant capsid protein fragment encoded by open-reading frame 65. HHV8 PCR analysis was negative while HHV8 serological studies showed an overall prevalence of 18% among patients suffering from sarcoidosis: 43% in patients from sub-Saharan Africa, 17% in patients from Northern Africa, 12.5% in patients from the French West Indies and 0% in French patients. In conclusion, our results do not indicate an association between HHV8 and sarcoidosis but reflect the seroepidemiology of this virus in different geographical regions.

Adult↗

Management of bleeding pseudoaneurysms in patients with pancreatitis.

BACKGROUND: Bleeding pseudoaneurysm is a rare but frequently fatal complication in patients with pancreatitis. METHOD: The medical records of ten patients who presented to this institution with a bleeding pseudoaneurysm between 1978 and 1997 were reviewed retrospectively. Six patients had chronic pancreatitis and four had acute pancreatitis. The splenic artery was involved in six cases, a pancreaticoduodenal artery in two, the gastroduodenal artery in one and the cystic artery in one. RESULTS: Computed tomography (CT) revealed the bleeding pseudoaneurysm in all patients (n = 6) with chronic pancreatitis but in only one of three with acute pancreatitis. Arteriography always gave the correct diagnosis. Seven patients underwent pancreatic resection as an emergency (n = 3) or within 48 h (n = 4), and survived. Three patients presenting with acute pancreatitis and massive bleeding underwent transcatheter arterial embolization. Two of them had a favourable outcome and one died from a recurrent haemorrhage 7 days later. Overall, two patients suffered significant perioperative complications and one died. CONCLUSION: CT is accurate in the diagnosis of pseudoaneurysms complicating pseudocysts. Primary resection of the pseudoaneurysm, which frequently requires pancreatic resection, is the treatment of choice. Angiography followed by transcatheter embolization is effective, but should be rapidly followed by operation.

Abdominal Pain↗

Clinical efficacy and safety of a topical combination of retinaldehyde 0.1% with erythromycin 4% in acne vulgaris.

The objective of this randomized, controlled, multicentre study was to assess the efficacy and safety of a topically applied retinaldehyde 0.1% gel in combination with a topical erythromycin 4% lotion for the treatment of acne vulgaris. Treatment consisted of applying either retinaldehyde or its vehicle every morning and erythromycin every evening for 8 weeks. Efficacy parameters were sequential lesion counts for papules and pustules, and a 6-point semiquantitative scale for comedones and microcysts. Safety parameters were local tolerance and adverse events. Of 74 recruited patients, 73 were appraisable for efficacy and safety. In both treatment groups, papules and pustules were reduced significantly at the end of treatment (P < 0.001), and no statistical difference was observed between the groups. Comedones and microcysts were significantly improved with retinaldehyde combined with erythromycin (P = 0.005), but not with erythromycin alone. However, no statistical difference between the groups could be demonstrated (test power, 50%). Local tolerance of the combined treatment group was very satisfactory, as only a few patients experienced local irritation. In conclusion, retinaldehyde combined with erythromycin appears to be a valuable topical therapy in polymorphic acne.

Acne Vulgaris↗

Decomplementation with cobra venom factor prolongs survival of xenografted islets in a rat to mouse model.

Although the involvement of complement in hyperacute rejection of xenotransplants is well recognized, its role in rejection of devascularized xenografts, such as pancreatic islets, is not completely understood. In this study, we investigated whether complement participates in the immunopathology of xeno-islet transplantation in a concordant rat to mouse model. Rat pancreatic islets were implanted under the kidney capsule of normal and cobra venom factor (CVF)-decomplementized diabetic C57BL/6 mice. Graft survival was monitored by blood glucose levels. Deposition of IgM and C3 on grafted islets in vivo or on isolated islets in vitro (after incubation with normal and decomplementized mouse serum), as well as CD4- and CD8-positive leucocyte infiltration of grafts, was checked by immunohistochemistry. In addition, complement-mediated cytotoxicity on rat islet cells was evaluated by a 3-(4, 5-dimethythiazolyl)-2.5-diphenyl-2H-tetrazolium-bromide (MTT) assay. A significant C3 deposition was found on grafted islets from the first day after transplantation in vivo, as well as on isolated islets after incubation with mouse serum in vitro. By MTT assay, complement-mediated cytotoxicity for islet cells was found. Decomplementation by CVF decreased C3 deposition on either isolated or grafted islets, delayed CD4- and CD8-positive leucocyte infiltration, led to significant inhibition of complement-mediated cytotoxicity for islet cells, and prolonged graft survival (mean survival time 21.3 versus 8.5 days; P<0.01). Our results indicate that decomplementation can prolong the survival time of devascularized xenografts across concordant species. The deposition of complement on transplanted islets may contribute to xenograft rejection by direct cytotoxicity and by promoting leucocyte infiltration.

Animals↗

Erythropoietin and preoperative autologous blood donation in the prevention of hepatitis C infection: necessity or luxury?

BACKGROUND: Prevention of exposure to allogeneic blood transfusion during surgery is an important financial issue when recombinant human erythropoietin (rHuEPO) is used in addition to preoperative blood donation. STUDY DESIGN AND METHODS: The aim of this study was to carry out a cost-effectiveness analysis of the use of rHuEPO in preoperative blood donation in orthopedic surgery. The study, based on a decision tree analysis of the use of rHuEPO, was conducted from the perspective of the French health care system. The efficacy criterion was the number of hepatitis C infections prevented. The decision tree analysis was constructed as follows: the residual risk of hepatitis C infection was 8.26 per million units transfused, and the chance node was defined according to the number of units transfused. RESULTS: With the use of rHuEPO in preoperative blood donation, 0.30562 cases of hepatitis C infection per 100,000 patients were prevented. The incremental cost of one prevented hepatitis C infection amounted to $888,000,000 (US). CONCLUSION: Despite the limitations of our model, the cost-effectiveness ratio was so large that variations only slightly modified the size of the result. From the societal perspective, it was not cost-effective to add rHuEPO to preoperative blood donation.

Blood Donors↗