Search PubMed⌕ Search

Biomedical subjects

P Morel

Publications and source records attributed to P Morel.

At least 55 records · Page 3Linked to original sources
PubMed2004

Short-term immunosuppression reduces fibrotic cellular infiltration around barium-M-alginate microbeads injected intraportally.

INTRODUCTION: One of the major barriers affecting the viability of encapsulated islets is pericapsular fibrotic infiltration (PFI). This study aimed to design strategies to reduce PFI around intraportally injected alginate microbeads. METHODS: Empty, highly purified, barium-M-alginate microbeads (400 microm) were injected intraportally into Lewis rats (3000 beads/rat). Rats (n = 9/group) were treated daily with either rapamycine (RAPA; 1 mg/kg/d p.o.), tacrolimus (TAC; 2 mg/kg/d p.o.), a combination of both, or gadolinium-chloride (GdC13, 20 mg/kg/d i.v., at day -1 and day +4). Treatment was discontinued at 10 days. Three rats/group were sacrificed at 3, 7, and 42 days after transplantation. Cellular composition of PFI was evaluated by immunohistochemistry. Severity of the reaction to the beads was determined by measuring the thickness of PFI on histology. RESULTS: The main cellular components of PFI in the liver were macrophages and myofibroblasts. There was a significant (P <.05) reduction in the thickness of PFI in all treated groups, even 6 weeks after transplantation. Encapsulated rat islets showed excellent insulin response to glucose in vitro, with a stimulation index of 3.6 +/- 2.0. CONCLUSION: Combination of highly purified alginate with short-term immunosuppression reduces fibrotic overgrowth around microbeads injected intraportally.

Alginates↗
PubMed2004

Optimization of neutral protease to collagenase activity ratio for islet of Langerhans isolation.

AIM: The optimal neutral protease to collagenase activity ratio has not been determined for islet isolation. We evaluated a new highly purified collagenase that can be blended with predetermined amounts of neutral protease (NP). METHODS: Islets were isolated from 7 groups of Sprague-Dawley rats. In group I, collagenase type XI (Sigma) at 2 mg/mL, and, in group II, Liberase at 0.6 mg/mL (2.4 PZ- U/mL; Roche) were used as controls. In groups III to VII, collagenase NB1 0.6 mg/mL (2.4 PZ-U/mL; Serva Electrophoresis) was used with increasing amounts of added NP. The NP to collagenase activity ratio (DMC-U/PZ-U) increased from 0.5% in group III to 2.0% in group VII. RESULTS: Mean islet equivalent (IE) yields per rat were 1367, 1755, 597, 895, 1712, 1043, and 905 in groups I to VII. IE yields were maximal at DMC-U/PZ-U = 1.2%. Islet morphology was influenced by NP concentration with decreasing numbers of trapped islets and increasing numbers of fragmented islets as NP contents increased. Cytokine release, islet cell apoptosis, and in vitro function were significantly better in groups III to VII as compared with groups I and II. CONCLUSION: NP is a crucial additive to collagenase for islet isolation. Optimization of the NP to collagenase activity ratio (1.2% in this model) improves yields and morphology after islet isolation.

Animals↗
PubMed2004

Microbial surveillance during human pancreatic islet isolation.

OBJECTIVES: The study aim was to investigate the microbiological safety of islet isolation and transplantation. MATERIALS AND METHODS: Between 1996 and 2002, prospective microbiological screening was performed on all pancreata procured for islet transplantation. Pancreas transport media and postpurification preparations were screened for microbiological contamination. Prior to isolation, pancreata were washed with either Hanks solution (group I, n = 170) or decontaminated with antiseptic and antimicrobial drugs (group II, n = 45). RESULTS: Microbiological contamination of the pancreas preservation media was shown in 62%. Analysis of the contaminants showed 74% gram-positive, 21% gram-negative organisms, and 5% fungi. The donor condition or procurement center did not influence the contamination rate. Longer pancreas transport duration was significantly associated with bacterial contamination (P <.05). In group I, 16 (9.4%) of 170 islet preparations presented microbial contamination at the end of the isolation procedures. Gram-positive organisms were present in 10 (6%), gram-negative organisms in 4 (2.4%), and fungi in 2 (1.2%) preparations. Four islet preparations (2.4%) from pancreata with noninfected transport medium were positive on postpurification cultures, all with gram-positive organisms. In group II, only 2 of 45 islet preparations (4.4%) presented microbial contamination at the end of the isolation process. CONCLUSIONS: The rate of microbial contamination during pancreas procurement and transport is high. Significant contaminants present when beginning islet isolation become undetectable by the conclusion of isolation. Diminishing the bio-burden by pancreas decontamination reduces the risk of contamination of the final islet preparation.

Animals↗
PubMed2004

Islet autotransplantation for the prevention of surgical diabetes after extended pancreatectomy for the resection of benign tumors of the pancreas.

OBJECTIVE: The objective of this article is to report a single-center experience with islet autotransplantation after extensive pancreatic resection for benign tumors of the pancreas. MATERIALS AND METHODS: Seven patients underwent extensive left pancreatectomy for benign lesions located at the neck of the pancreas. Once an unequivocal diagnosis of a benign nature was ascertained, the rest of the specimen was processed and the unpurified pancreatic digest was infused into the portal vein. The results were compared with those of 8 autotransplantations performed for chronic pancreatitis over the same period. RESULTS: Tumors were 4 cystadenomas, 2 insulinomas and 1 neuroendocrine tumor. Mean islet yields were 275,000 islet equivalents (IEQ) versus 129,000 in chronic pancreatitis (P =.04) or 6700 IEQ/g of tissue versus 1900 (P =.002), resulting in transplantation of 4200 IEQ/kg body weight vs 2150 in chronic pancreatitis (P =.03), respectively at 4-month to 7.5-year follow-up, all patients are alive and 6 of 7 are off insulin. All patients off insulin after at least 1 year currently have a normal IVGTT, with K values ranging between -1.19 and -2.36 (normal < -1.00). All patients, including 1 on insulin, display positive basal and glucagon-stimulated C-peptide levels. CONCLUSIONS: Compared with chronic pancreatitis tissue resected for benign tumors is more likely to achieve good islet yields, and thus insulin independence after autotransplantation. Islet autotransplantation should be considered when extensive pancreatectomy is required for resection of a benign tumor, and only if the benign nature of the lesion is demonstrated unequivocally.

Aged↗
PubMed2004

Islet of Langerhans allogeneic transplantation at the University of Geneva in the steroid free era in islet after kidney and simultaneous islet-kidney transplantations.

AIMS: We report a single-center experience of islet allogeneic transplantation in islet after kidney (IAK) and simultaneous islet-kidney (SIK) type 1 diabetic recipients using a steroid-free immunosuppressive regimen. METHODS: Eight patients received 12 islet infusions in 5 IAK and 3 SIK procedures. Median age was 51 years (range, 30-58 years) with a male:female ratio of 2:6. IAK was considered only for patients with a stable kidney function and a creatinine clearance level >60 mL/min. SIK was considered for patients with a counterindication for simultaneous kidney-pancreas transplantation. Immunosuppression was based on sirolimus/tacrolimus combined with daclizumab induction. Two consecutive infusions of >5000 islet equivalents (IEQ)/kg were planned. RESULTS: Five patients completed the transplantation course, whereas 3 patients received only 1 islet infusion. All patients have functional grafts (C-peptide >166 pmol/L) at 6-month median follow-up. Of 5 patients who completed their transplantation course 4 became insulin independent. HbA1c and fructosamine decreased over time, showing improved metabolic control. Severe adverse events were observed in 4 patients. One SIK patient died after OKT-3 treatment of severe kidney rejection. CONCLUSIONS: The Edmonton immunosuppressive protocol can be applied for patients undergoing either IAK or SIK procedures, with a high rate of graft function and insulin independence. Morbidity is higher than among patients undergoing solitary islet transplantation for type 1 brittle diabetes.

Adult↗
PubMed2004

Successful islet after kidney transplantations in a distance over 1000 kilometres: Preliminary results of the Budapest-Geneva collaboration.

To overcome critical islet processing and to ensure patient safety and quality care, we have established an international collaboration between two geographically distant transplant centers for islet transplantation. Four pancreata were harvested and immediately preserved by the two-layer method (oxygenated perfluorocarbon+University of Wisconsin) and subsequently transported for the automated method isolation to Geneva. After purification, the islets were cultured overnight and transported the next day back to Budapest. Three consecutive kidney transplant patients with type 1 diabetes mellitus underwent islet transplantation via percutaneous transhepatic portal embolization using the bag-method. The immunosuppression consisted of daclizumab, sirolimus, and low-dose tacrolimus. Mean donor age was 43.7 years, mean body mass index: 26.5. The islet isolation process began within 8 hours from the donor aorta cross-clamp in all cases. The isolation success rate was 80% (4 of 5). In Budapest, the islets were assessed for viability. No complications occurred during the transplantation, and the portal pressure remained within the normal range. The first patient received 12,000 IU/BW from two donors and the insulin requirement decreased from 40 U/d to 10 U/d. The second patient received 7200 IU/BW from a single donor and became immediately insulin free. The third patient was given 7100 IU/BW; the insulin requirement decreased from 39 U/d to 14 U/d. Posttransplant follow-up for the three patients are 7 months, 4 months, and 2 weeks, respectively. All patients achieved metabolic stability. These preliminary results demonstrate the feasibility of an international collaborative islet transplantation program at a distance over 1000 km.

Adult↗
PubMed2004

[Discoid lupus erythematosus involving the eyelids: 4 cases].

BACKGROUND: Discoid lupus erythematosus is a chronic skin disease frequently involving the face, scalp and ears. Palpebral lesions are rare. We report 4 cases of this uncommon localization. In one case, palpebral lesions were the sole manifestation of the discoid lupus erythematosus. CASE REPORTS: Four patients aged between 26 and 45 Years had lesions of the lower eyelid as erythematous, infiltrated and scaly plaques. One patient, without diagnosis despite 2 skin biopsies of lesion, presented with a 2-Year history of blepharitis in the absence of any other cutaneous abnormality. In one case, chronic blepharitis has been present for 4 Years and associated with inflammatory arthralgia. Alopecia occurred 4 Years after the onset of blepharitis and led to the diagnosis of discoid lupus erythematosus. In 2 cases, blepharitis was associated with typical cutaneous lesions of discoid lupus erythematosus. Antimalaria drugs were very effective in 3 cases. In one patient the antimalaria drug failed, but thalidomide was effective. DISCUSSION: The location of lesions on the eyelids in the absence of any other cutaneous abnormality is rare and can easily lead to the misdiagnosis of discoid lupus erythematosus. Most Authors mention a predilection of the lesions to the inferior portion of the eyelid, more specifically to the external third. The involvement of the eyelids with permanent scarring and severe eye impairment is explained by the long duration of the disease without diagnostic and appropriate treatment. Clinical examination is highly consistent with discoid lupus erythematosus: the lesions typically present as well-circumscribed, erythematous plaques with telangiectasia and scales and atrophy in long-standing disease. Antimalaria drugs are remarkably effective.

Adult↗
PubMed2004

[Photochemotherapy for pityriasis lichenoides: 3 cases].

BACKGROUND: Pityriasis lichenoides is a rare cutaneous disorder of unknown origin that mainly affects children and young people. The disease consists of two variants: pityriasis lichenoides et varioliformis acuta, characterized by papular lesions evolving into necrosis and pityriasis lichenoides chronica characterized by scaly papules that may last from several months to several years. Various types of therapy have been proposed for pityriasis lichenoides, to our knockledge, photochemotherapy has never been used. We report the first 3 cases of pityriasis lichenoides treated by photochemotherapy. CASE REPORTS: Three patients, 6, 15 and 18 years old, presented respectively with a 1 month, 2 years and 3 months history of numerous, papular and necrotic lesions or squally papular lesions. Clinical appearance and histopathologic examination of biopsy were consistent with pityriasis lichenoides et varioliformis acuta (patients 1 and 3) and with pityriasis lichenoides chronica (patient 2). They had received different treatments without significant effect: topical corticosteroids, antibiotic, UVB therapy and dapsone. Acitretin associated with PUVA were dramatically effective within few weeks. DISCUSSION: Pityriasis lichenoides can be a severe scarring disease with significant social, psychological and physical consequences. In our opinion, photochemotherapy, which has never been used in pityriasis lichenoides, is effective. Therapeutic modalities have to be define.

Acitretin↗
PubMed2004

High-dose therapy and autologous stem cell transplantation in relapsing cutaneous lymphoma.

Treatment of cutaneous T-cell and B-cell lymphomas is difficult and relapses are frequent. To evaluate the efficiency of high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) on relapsing cutaneous lymphomas, we conducted a retrospective study of 14 patients. We investigated the clinical and histological parameters of the lymphoma, previous treatments to ASCT, short-term complications of ASCT, and occurrence of a relapse. There were 11 males and three females, with a median age of 42 years. Most often, the skin disease was disseminated without extracutaneous involvement. Four patients had a B-cell lymphoma and 10 a T-cell lymphoma. CD30 was negative in 8/10 T-cell lymphomas. Before ASCT, 13 patients had chemosensitive disease; one had refractory disease. The conditioning regimen included TBI in nine cases. No toxic death occurred. Relapse of the lymphoma occurred in eight cases (T-cell lymphoma in seven cases), within 4 months after ASCT in six cases. Relapses were treated with local treatment, interferon or classical chemotherapy. At the end of the study, 11 patients were alive and three patients had died. HDT and ASCT do not benefit patients with T-cell lymphomas. For patients with disseminated relapsing cutaneous B-cell lymphomas, this procedure should be considered.

Adult↗
PubMed2004

Relationship between sympathetic reactivity and body weight loss in morbidly obese subjects.

OBJECTIVE: To investigate the possible role of peripheral sympathetic activity in gastric bypass-induced body weight loss. SUBJECTS AND METHODS: In 42 morbidly obese patients (sex: 36 f/6 m; BMI: 46.0+/-0.7 kg/m(2)) undergoing a gastric bypass, the skin vasoconstrictor reflex in answer to a deep inspiration was measured by laser Doppler fluximetry. The extent of vasoconstriction, measured at the second finger of the left hand, was expressed as percent reduction of the basal blood flux (% vasoconstriction). Insulin sensitivity was assessed before surgery in a subset of patients (n=11), by the method of euglycemic, hyperinsulinemic clamp. Body weight and composition were evaluated before, and 3, 6 and 12 months after surgery. At the same time points, energy intake (kJ/day) was evaluated by means of both food record diary and alimentary anamnesis. RESULTS: The % vasoconstriction, which was significantly (P=0.01) greater in normoglycemic subjects than in diabetic ones, was also significantly (P=0.03) related to the extent of insulin sensitivity measured during the euglycemic clamp. The % vasoconstriction showed a significant (P>0.0001), positive correlation with weight reduction obtained between the 6th and 12th months following surgery; as a consequence, % vasoconstriction was significantly (P=0.0004) related to the overall body weight loss achieved during the year following the operation. These correlations remained significant in multiple regression analysis with adjustment for age, initial body weight, plasma glucose and insulin (P=0.0007 and 0.006, respectively). The % vasoconstriction was also significantly (P=0.0006), negatively related to energy intake measured 12 months after surgery. CONCLUSIONS: In conditions of stable body weight, the sympathetic nervous system (SNS) reactivity is influenced by the degree of insulin resistance. A high capacity to activate the SNS, measured before surgery, is associated with both a larger gastric bypass-induced weight loss and a lower energy intake, at the phase of weight stabilization.

Adult↗
PubMed2004

Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer.

BACKGROUND: In advanced metastatic colorectal adenocarcinoma, the addition of a neo-adjuvant systemic treatment to surgery might translate into a survival advantage, although this is yet to be confirmed by ongoing randomized trials. The objective of this study was to assess the effects of preoperative systemic chemotherapy on the morphology of non-tumoral liver. PATIENTS AND METHODS: A large series of surgically resected liver metastases (n=153) was selected. Light microscopy, electron microscopy, and immunohistochemistry using antibodies against endothelial cells (CD31) and hepatic stellate cells (alpha-SM actin, CRBP-1) were performed to identify sinusoidal wall integrity. RESULTS: We found that 44 (51%) of the 87 post-chemotherapic liver resection specimens had sinusoidal dilatation and hemorrhage, related to rupture of the sinusoidal barrier. In contrast, the 66 livers treated by surgery alone remained normal. In 21 out of the 44 post-chemotherapy patients (48%), perisinusoidal and veno-occlusive fibrosis also developed. Sinusoidal injury persisted several months after end of chemotherapy, and fibrosis may progress. Development of lesions was strongly correlated to the use of oxaliplatin; 34 out of 43 patients (78%) treated with this drug showed striking sinusoidal alterations. CONCLUSIONS: Systemic neo-adjuvant chemotherapy in metastatic colorectal cancer frequently causes morphological lesions involving hepatic microvasculature. Sinusoidal obstruction, complicated by perisinusoidal fibrosis and veno-occlusive lesion of the non-tumoral liver revealed by this study, should be included in the list of the adverse side-effects of colorectal systemic chemotherapy, in particular related to the use of oxaliplatin.

Adenocarcinoma↗
PubMed2004

Idiopathic systemic capillary leak syndrome: cutaneous involvement can be misleading.

BACKGROUND: Systemic capillary leak syndrome (SCLS) is a severe disorder characterized by unexplained rapid transfer of considerable volumes of plasma from the intravascular to the extravascular compartment. For some cases of SCLS, no aetiology is evident and these cases are reported as idiopathic (ISCLS). OBJECTIVES: To describe the cutaneous findings in 3 patients with ISCLS. RESULTS: Cutaneous involvement consisted in sclerosis, livedo, purpura and photodistributed maculopapular erythematous rash. Dermal mucinosis was proven by biopsy in 1 patient. No underlying disease was diagnosed during follow-up. CONCLUSION: The above-mentioned cutaneous findings can be present during acute attacks of ISCLS. They seem specifically related to the ISCLS and not indicative of an underlying disease.

Aged↗
PubMed2003

Human herpesvirus 8-associated hemophagocytic lymphohistiocytosis in human immunodeficiency virus-infected patients.

We retrospectively reviewed 5 cases of hemophagocytic lymphohistiocytosis (HL) associated with human herpesvirus 8 (HHV-8) reactivation in human immunodeficiency virus (HIV)-infected patients. All patients had clinical and biological features characteristic of HL. Pulmonary symptoms were present in all patients and were frequently life threatening. The mean number of HL episodes was 6. Four patients had HL-associated Kaposi sarcoma, and 3 had multicentric Castleman disease. The mean CD4 cell count was 200 cells/mm(3). HIV loads were stable in all patients. All patients had high levels of HHV-8 in peripheral blood mononuclear cells during attacks, and a significant increase in this parameter before the attacks was seen in 3 patients. Although 2 patients died of HL, 3 are still alive and receiving etoposide therapy (mean follow-up, 3 years). HHV-8-related HL is associated with life-threatening symptoms and biological HHV-8 reactivation, and it may be controlled in the long term by etoposide therapy combined with highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed2003

[Transfusion-transmitted bacterial infection: residual risk and perspectives of prevention].

Bacterial contamination of blood components represents today the highest infectious risk of blood transfusion, the risk is particularly high when it affects platelet concentrates. The residual risk of transfusion reaction due to bacterial contamination of platelets concentrates remains stable. For all severity 1 case occurs with 25,000 distributed platelets concentrates and 1 death occurs with 200,000 distributed units. In France, efforts have focused on the prevention of contamination during donation--involving measures such as rejecting the first few millilitres of donated blood and improving skin disinfection--and the prevention of bacterial proliferation in platelets concentrates--notably by removing leukocytes and ensuring high-quality storage of donated blood. 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). There is currently considerable debate about the relative importance of bacterial screening methods and methods for inactivating pathogens present in PC. Automated culture (Biomérieux) and the ScanSystem (Hemosystem) and BDS (Pall) method are the most advanced detection systems available, to our knowledge. In term of pathogen inactivation system for platelets, Intercept (Baxter) is nearing the commercial market. These new prevention have logistic and/or functional consequences that will require close scrutiny methods. A national study group is currently considering the consequences of each of these methods and should give its opinion at the end of the first half of 2003.

Bacterial Infections↗
PubMed2003

A tale of two colons and two cancers. Distinct carcinogenesis and clinical outcome according to location proximal or distal to the splenic flexure.

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.

Cell Transformation, Neoplastic↗
PubMed2003

Adult lymphoblastic lymphoma: a retrospective analysis of 92 patients under 61 years included in the LNH87/93 trials.

Since 1987, the GELA has initiated multicenter prospective trials for aggressive non-Hodgkin's lymphomas (NHL). Lymphoblastic lymphomas (LBL) were included in those studies until 1997, and 92 LBL patients under 61 years were identified after histological review. The protocols prescribed high-dose anthracycline regimens, four cycles given every 15 days as induction and lasted for </=6 months. A total of 23 patients underwent high-dose therapy consolidation followed by autologous stem-cell transplantation and 69 received standard chemotherapy regimens. Clinical characteristics showed a male predominance (66%) with a median age of 31 years, bone marrow (BM) involvement (22%), mediastinal involvement (66%) and elevated LDH (62%). At the end of treatment, it was seen that 71% of the patients achieved complete remission; four (4%) patients died during induction; 43 patients relapsed at a median time of 10 months. With a median follow-up of 34 months, the 5-year overall survival (OS) and event-free survival (EFS) rates were 32 and 22%, respectively. The only favorable factor significantly associated with survival was young age. These results are poorer than those obtained in other aggressive lymphomas treated with the same regimens and suggest that adult LBL patients should be treated with acute lymphoblastic leukemia protocols.

Adolescent↗