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Biomedical subjects

P Morel

Publications and source records attributed to P Morel.

At least 19 recordsLinked to original sources

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↗

[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↗

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↗

Neoadjuvant radiochemotherapy for locally advanced gastric cancer: a phase I-II study.

BACKGROUND: To study in a phase I-II trial the maximum tolerated dose, the toxicity, and the tolerance of adding radiotherapy to systemic chemotherapy administered preoperatively in patients with locoregionally advanced gastric adenocarcinoma. PATIENTS AND METHODS: Patients with adenocarcinoma of the stomach (T(3)(-)(4)N(any) or T(any)N+), performance status </=1, normal hematological, hepatic and renal functions received two cycles of cisplatin 100 mg/m(2) on day 1, 5-FU 800 mg/m(2) on days 1 to 4 and leucovorin 60 mg b.i.d. on days 1 to 4 q3w, concomitantly with radiation therapy escalated in three dose tiers (31.2, 38.4 and 45.6 Gy). RESULTS: Nineteen patients were accrued and 18 completed neoadjuvant therapy. Major toxicity consisted of grade 3/4 leucopenia and mucositis in 89% and 36% of the patients, respectively. Only one episode of febrile neutropenia was recorded. Dose level number 2 (38.4 Gy) with the chemotherapy given q4w is the recommended dose level. All patients were subsequently operated and no fatalities occurred. Pathological assessment showed one complete and eight partial responses. Two- and 3-year relapse-free survival rates were 57% and 50%, respectively. Only one patient relapsed locally. The peritoneum was the most frequent site of relapse. CONCLUSIONS: This neoadjuvant therapeutic program is relatively well tolerated, does not seem to increase the operative risk, and might increase the locoregional control of the disease. The frequency of peritoneal involvement in relapsing patients underscores the need for a more effective systemic treatment.

Adenocarcinoma↗

Four year nutritional follow up after living related small bowel transplantation between monozygotic twins.

While small bowel transplantation (SBTX) may allow parenteral nutrition independence in the case of short bowel syndrome, its effects on body composition and growth are unclear. For the first time, a paediatric living related SBTX was performed between monozygotic twins. This case report describes their four year nutritional follow up. The 13 year old recipient and his healthy brother underwent measurements of body composition by 50 kHz bioimpedance analysis and bone mineral density of the femoral neck and total femur by dual energy x ray absorptiometry. Xylose tests and measurements of faecal fat evaluated gut absorption. All tests were performed before and after SBTX. Body weight increased from 34.7 to 51.9 kg in the recipient and from 45.0 to 53.2 kg in the donor within four years. The recipient caught up with the height and fat free mass of his brother within two years. Fat mass, and total femur and femoral neck densities are still lower in the recipient than in the donor four years after SBTX (-1.2 kg, -0.087 g/cm(2), -0.035 g/cm(2)). The xylose test of the recipient was still abnormally low after four years (1.37 mmol/l) and faecal fat was high until two years after SBTX (March 2001: 12 g/24 h). The donor always showed normal xylose tests and faecal fat, except for one episode of high faecal fatty acids about 10 months after SBTX. SBTX improved the nutritional state and growth of the graft recipient although body composition, femoral bone mineral densities, and intestinal absorption had not completely normalised after four years.

Adolescent↗

Impact of integrin-matrix matching and inhibition of apoptosis on the survival of purified human beta-cells in vitro.

AIMS/HYPOTHESIS: Human islet cells survive poorly in culture and are overgrown by non-endocrine cells. The aims of this study were to sort human beta cells and to develop approaches for their improved survival in culture. METHODS: Human islets were infected with recombinant adenovirus expressing green fluorescent protein (GFP) under the control of the rat insulin promoter such that only beta cells expressed GFP. GFP-positive beta cells were sorted by flow cytometry, and expression of select integrins evaluated by RT-PCR. Beta cells were cultured on different extracellular matrices for up to 15 days. Apoptosis was measured by annexin V binding and ELISA. Insulin secretion was measured by ELISA. RESULTS: Sorted beta cells survived less well in culture than unsorted islet cells. This did not appear to be due to adenoviral infection and/or GFP expression. Purified beta cells expressed the integrins alpha 3, alpha 5, alpha 6, alpha V, beta1, but not beta 4. Of the various matrices tested, sorted beta cells attached and spread best on a lawn of lysed human bladder carcinoma cells (5637 cells). However, survival remained poor. Cell death was decreased but not prevented by continued presence of 10 mmol/l nicotinamide and apoptosis decreased by 24 h incubation with 20 micromol/l Z-VAD. Insulin secretion was maintained over 6 days following treatment with both agents. CONCLUSIONS/INTERPRETATION: Purification of human beta cells induces marked apoptosis limiting their function and survival in vitro. This was improved by matching the extracellular matrix to the specific expression of integrins and by addition of nicotinamide and Z-VAD.

Adult↗

Topical use of cidofovir induced acute renal failure.

BACKGROUND: Cidofovir has antiviral activity against a wide spectrum of DNA viruses. Several small studies have focused on the efficacy of topical cidofovir in various viral-induced diseases. We report a systemic complication of such therapy. CASE REPORT: A bone marrow transplant recipient with chronic renal failure developed genital condylomas resistant to standard therapy. After topical cidofovir application (1% once daily for 5 days, then 4% for 12 days), the lesions improved while local erosions appeared. Acute renal failure with features of tubular acidosis occurred at day 19. Spontaneous recovery was observed after cidofovir withdrawal. CONCLUSION: We describe for the first time acute renal failure after topical cidofovir in an immunosuppressed patient with prior renal insufficiency. This method of administration should be avoided on abraded skin and should be carefully monitored.

Acute Kidney Injury↗

[Detection of bacterial contamination in platelet concentrates: perspectives].

Bacterial contamination of blood components represents today the highest infectious risk of blood transfusion, the risk is particularly high when it affects platelet concentrates. In France the prevention methods developed over the past six years (donor selection, phlebotomy site preparation, first 30 ml diversion, systematic leuko-reduction...) aimed at limiting the introduction of bacteria in blood and bacterial proliferation. Several methods have been tested for the detection of bacterial contamination in platelet concentrates but none have been generalised. Difficulties were met, due to the necessity of 1) detecting only the platelet concentrates presenting a real infectious risk, when the presence of bacteria is observed in 2.2% (2-4%) of donated blood and 2) guaranteeing the availability of platelet concentrates. New methods have been developed which seem able to bring responses to these difficulties. Several processes are being (or will be) assessed, including automated blood culture, bacterial genomic detection with or without amplification, flow cytometric methods. In parallel, an indirect method able to detect the presence of bacteria, based on oxygen consumption, will also be evaluated. One (or several) of these processes should allow, in the short-term, to detect platelet concentrates presenting an infectious risk. In the future, the interest of bio-chips for bacterial detection in biological fluids must be investigated.

Bacteria↗

Melanoma progression and serum L-dopa/L-tyrosine ratio: a comparison with S100B.

The challenge to find a reliable tumour marker for the management of melanoma patients still remains. In this study, the serum L-dopa/L-tyrosine ratio was compared with serum S100B as a reference marker. A total of 89 melanoma patients were sampled and staged according to the American Joint Committee on Cancer (AJCC) classification. Of these, 19 stage III and 28 stage IV patients were evaluated for disease progression at 1.5 years and 6 months post-sampling, respectively. Serum L-dopa and L-tyrosine were measured by high performance liquid chromatography (HPLC) (normal value for ratio < 16 x 10(-5)) and S100B using the LIA-mat Sangtec 100 assay (normal value < 0.10 microg/l). Non-parametric tests (Kruskal-Wallis analysis of variance, Dunn's and Spearman) were used for the statistical analysis. The median serum L-dopa/L-tyrosine ratio was 16.0 x 10(-5) (range 2.7-545.1 x 10-5 and the median S100B level was 0.15 microg/l (range < 0.10-13.8 microg/l), with a sensitivity of 51% for the ratio and 66% for S100B. There was a 47% discordance and no correlation between the two markers (r = 0.149). The ratio was higher in stage IV than in other stages (P < 0.05), as was the S100B level (P < 0.0001). Both markers were higher in patients with evolutive disease (n = 23) than in stable patients (n = 24), with values of 20.8 x 10(-5) versus 13.1 x 10(-5) for the ratio (P < 0.05) and 0.89 microg/l versus 0.16 microg/l for S100B (P < 0.001); for the ratio, this difference was more pronounced in stage III than in stage IV patients. The overall sensitivity and specificity of the markers to predict disease progression were 78% and 67%, respectively, for the ratio, and 74% and 83%, respectively, for S100B (using an ROC cut-off of 0.38 microg/l). In conclusion, the serum L-dopa/L-tyrosine ratio correlates with melanoma progression and has predictive value, especially in stage III patients. This tumour marker, like S100B, could serve as an additional tool in the management of melanoma.

Adult↗

[Abstract quality assessment of articles from the Annales de Dermatologie].

INTRODUCTION: Article's abstracts are an important part of the publication, widely available in electronic databases. We assessed the quality of abstracts in the Annales de Dermatologie. The main objective was to compare abstract quality in 3 periods in the past decade. In this Journal, structured abstracts are required since 1993. The secondary objective was to compare structured and non structured abstract quality. MATERIAL AND METHODS: Three periods were assessed: 1991-92, 1996 and 2000. We selected the abstracts of original studies, excluding non focused descriptive case series. We used a criteria scale elaborated by Narine et al. Thirty criteria were assessed for each abstract, divided into 8 categories: purpose, research design, setting, subjects, intervention, outcome measurement, results and conclusion. If applicable to the study, a criterion was rated 1 (present) or 0 (absent). The final score for each abstract was defined as the ratio of positive answers among rated criteria. Mean scores for each period were compared using analysis of variance (mean +/- standard deviation). The temporal trend was calculated by simple linear regression. The mean scores of structured and unstructured abstracts were also evaluated and then compared. RESULTS: For each period, chronologically, 8, 17 and 18 (total 43) abstracts were evaluated. Mean scores for each period were 0.72 +/- 0.20 (1991-92); 0.69 +/- 0.12 (1996) and 0.83 +/- 0.08 (2000). These 3 scores were significantly different (P=0.006), with a trend toward increasing (Regression coefficient R(2)=0.136; P=0.015). Research setting obtained the lowest score (0.4). Structured (0.72 +/- 0.20; n=35) and non structured abstracts (0.76 +/- 0.12; n=8) were not significantly different. DISCUSSION: Abstracts of articles published in the Annales de Dermatologie contained on average 3/4 of the required informative items. The trend toward better scores may be explained by an increased attention of the editorial board as well as authors and reviewers. The quality could be improved by systematically mentioning the research setting.

Abstracting and Indexing↗