Search PubMed⌕ Search

Biomedical subjects

D Morel

Publications and source records attributed to D Morel.

At least 19 recordsLinked to original sources
PubMed2006

Identification of circulating CD10 positive T cells in angioimmunoblastic T-cell lymphoma.

In most cases of lymphomas with blood dissemination, the careful cytological analysis of peripheral blood smears provides a rapid orientation to diagnosis, even if the final subtyping is achieved by histology and eventually other techniques. Here, we evaluated if the analysis of blood smears may suggest the blood dissemination of angioimmunoblastic T-cell lymphoma (AITL) and if CD10 expression on neoplastic T cells, as recently reported on AITL, may contribute to the diagnosis. In all, 11 lymph nodes and six peripheral blood samples from 12 patients with AITL were studied using four-colour flow cytometry associated to histological, cytological and molecular data. According to previous results, a fraction of T cells expressed CD10 in 10/11 lymph nodes. Interestingly, all blood smears showed atypical lymphoid cells and a fraction of T cells expressed CD10 with a mean percentage of 18.75% (range 5.00-47.00%), regardless of lymphocytosis level and of rate of CD10 T cells in corresponding lymph node. In contrast, in all control samples (100), none CD10-positive T cell was identified. This is to our knowledge the first description of circulating CD10 neoplastic T cells in AITL. Therefore, they ought to be explored in further studies when aggressive lymphoma, in particular with lymphopenia and circulating atypical cells, is suspected.

Adult↗
PubMed2005

Cytogenetic analysis delineates a spectrum of chromosomal changes that can distinguish non-MALT marginal zone B-cell lymphomas among mature B-cell entities: a description of 103 cases.

The purpose of this study was to document the frequency and distribution of karyotypic changes present at diagnosis in 103 non-MALT marginal zone cell lymphoma (MZL) patients. This cytogenetic analysis of a large cohort extends previous observations and allows the identification of new cytogenetic features. Abnormalities identified in more than 15% of patients included +3/+3q (37%), 7q deletions (31%), +18/+18q (28%), 6q deletions (19%), +12/+12q (15%) and 8p deletions (15%). Trisomy 3/3q, 7q deletions, +18 and +12 were seen in different combinations in more than 30% of patients in comparison to 2% in lymphocytic lymphomas/chronic lymphocytic leukemias, 1% in mantle cell lymphomas and 7% in follicular lymphomas. The marked propensity of these abnormalities to be recurrently associated with the same tumoral clone of individual karyotypes allowed the delineation of a cytogenetic profile that may help to distinguish non-MALT MZL among other mature B-cell neoplasms. If +3/3q, +12/+12q, and 6q, 7q and 8p deletions were significantly associated with clinical prognostic factors previously reported to influence survival and time to progression, patients displaying these abnormalities did not experience a significantly shorter time to progression.

Adult↗
PubMed2004

An unusual endocarditis-induced crescentic glomerulonephritis treated by plasmapheresis.

A 58-year-old man presented with fever and a rapidly progressive glomerulonephritis. An infective endocarditis due to Streptococcus parasanguis was diagnosed. A renal biopsy revealed type III pauci-immune crescentic glomerulonephritis. As first-line therapy, antibiotics were administered alone. Faced to the unsuccessful anti-infective approach, corticosteroid therapy was added as a second-line therapy. Finally, plasmapheresis introduced as the third-line therapy, significantly improved renal function. This case is an original type III rapidly progressive glomerulonephritis, since ANCA were repeatedly found negative. In very few cases, plasmapheresis was successfully used for the treatment of infective endocarditis-induced crescentic glomerulonephritis. The pathophysiology and the potential efficiency of plasmapheresis are discussed.

Endocarditis, Bacterial↗
PubMed2002

[Efficacy of C1-C2 block with posterior parasagittal approach in the treatment of Arnold neuralgia in 24 patients].

UNLABELLED: The purpose of the study is to evaluate the efficacy of C1-C2 block from a posterior parasagittal approach to treat Arnold neuralgia. MATERIALS AND METHODS: 24 patients have been interviewed after 33 blocks were performed. The mean delay was 22 months. The posterior approach had always been performed using fluoroscopy. 27 blocks were performed with Hydrocortancyl((R)), 6 with Altim((R)). RESULTS: 71% of patients were symptomatically improved after one month, 62% after 3 months and more than 50% after one year. Using a visual analogue scale, pain was reduced of 5.8, i.e. 70% of patients were improved. An important reduction of pain killer requirements was noted for improved patients, patients with pain recurrence asked for a new infiltration. No significant side effect was noted. CONCLUSION: Our method seems to be an efficient alternative to blocks performed on the origin of the nerve and to surgical treatment.

Adult↗
PubMed2002

[Pain management with nerve root block under ct and neurostimulator guidance].

PURPOSE: To evaluate the efficacy of nerve roots block under CT and neurostimulator guidance for the management of pain. MATERIAL: and method. Nerve root blocks were performed in 27 patients (pudendal nerve, intercostal nerve, ilio-hypogastric nerve, thoracic and lumbar sympatholysis). These were performed with corticosteroids (Altim((R))) (20 patients) or phenol (7 patients). RESULTS: Seventeen patients (63%) had pain reduction during at least 15 days. The pain relief was longer with phenol. Complications appeared in the 3 lumbar sympatholysis (inguinal pain) and one of the thoracic sympatholysis (Claude Bernard Horner syndrome). CONCLUSION: The nerve root blocks seem to have some efficacy and a further evaluation is necessary to assess their impact on the ability of patients to return to work and their need for pain medication. When performing these procedures, one must be careful to avoid potential complications and verify that the procedure is needed.

Adult↗
PubMed2001

[mTOR and FTY 720 inhibitors].

SIROLIMUS: The leading member of the mTOR inhibitor family, sirolimus or rapamycin, has dose-dependent side effects that can generally be well controlled. Sirolimus can be combined with tacrolimus at therapeutic doses; likewise for the sirolimus-cyclosporine combination at moderate dosage. Effective plasma concentrations of sirolimus vary from 5 to 20 ng/ml depending on the combination of immunosuppressant agents used. Sirolimus has been shown to inhibit metastatic diffusion of renal adenocarcinoma in the mouse. Its complex side effects on angiogenesis, fibrosis processes and chronic rejection are still being investigated. EVEROLIMUS: Everolimus, or RAD, has a very short half-life, but induces fewer hematologic effects. The therapeutic dose must reach at least 3 ng/ml to prevent rejection. Doses above 15 ng/ml increase the risk of thrombocytopenia. FTY 720: A new immunosuppressant agent, FTY 720, does not belong to any known family. It has a totally different mechanism of action compared with currently available immunosuppressants. FTY 720 increases the expression of chemokine receptors on the surface of T cells making them unavailable for the rejection reaction. FTY 720 has a very long half-life (108 hours). Due to its particular liver metabolism, there is a very low risk of drug interactions.

Cyclosporine↗
PubMed2001

A proliferation control network model: the simulation of two-dimensional epithelial homeostasis.

Despite the recent progress in the description of the molecular mechanisms of proliferation and differentiation controls in vitro, the regulation of the homeostasis of normal stratified epithelia remains unclear in vivo. Computer simulation represents a powerful tool to investigate the complex field of cell proliferation regulation networks. It provides huge computation capabilities to test, in a dynamic in silico context, hypotheses about the many pathways and feedback loops involved in cell growth and proliferation controls. Our approach combines a model of cell proliferation and a spatial representation of cells in 2D using the Voronoi graph. The cell proliferation model includes intracellular (cyclins, Cyclin Dependent Kinases - CDKs. Retinoblastoma protein - Rb, CDK inhibitors) and extracellular controls (growth and differentiation factors, integrins). The Voronoi graph associates a polygon with every cell and the set of these polygons defines the tissue architecture. Thus, the model provides a quantitative model of extracellular signals and cell motility as a function of the neighborhood during time dependent simulations. The 2D simulations illustrate the influence of the microenvironment on cell proliferation in basal layers of stratified epithelia and of differential adherence in keratinocytes differentiation and related upward migration. Our results particularly show the role of CDK inhibitors (mainly the protein p27) in the Rb dependent control pathway of the transition from the G1 to S phase of the cell cycle.

Cell Cycle↗
PubMed2001

Long-term (> or =20 yr) status of 14 cadaveric kidney-transplant recipients.

The aim of this study was to analyze the status of patients with a successful long-term (> or =20 yr) kidney graft. Nineteen (8.1%) of the 234 recipients who received a cadaveric kidney transplant between 1968 and 1978 in our center are still alive 21.7+/-1.6 yr (mean+/-standard error of the mean) later with a functioning allograft. Function, including measurement of the renal functional reserve (RFR), histological status, and morbidity were evaluated. Fourteen patients agreed to participate in this study. Their current immunosuppressive regimens combined prednisone (P)+azathioprine (AZA) (n=9), P+AZA+cyclosporine (CsA) (n=3) or P+CsA (n=2). Although they described their quality of life as good, 10 patients had mild hypertension, 5 developed 10 malignancies (9 cutaneous), 5 had replicative hepatitis, 8 had osteopenia, and 6 had cataracts, but none had diabetes mellitus. Proteinuria was detected in 6 patients, but was always less than 1 g/d. Mean serum creatinine was 1.28+/-0.28 mg/dL and glomerular filtration rate was 54.5+/-5.3 mL/min/1.73 m2. RFR was present for 4 patients with a mean value of +14.8+/-1.9 mL/min. Their functional status was not correlated with the histological lesions observed in concomitant transplant biopsies. Kidney grafts are able to function well even more than 20 yr post-transplantation, with some having a RFR whose significance remains unknown. Morbidity is of minor clinical severity, but could be further reduced with optimized management. Moreover, transplantation is much less costly than hemodialysis.

Adult↗
PubMed2000

Type IV phosphodiesterase inhibitor is effective in prevention and treatment of experimental crescentic glomerulonephritis.

BACKGROUND: Tumour necrosis factor alpha (TNF-alpha) has an important role in acute glomerular inflammation. Rolipram, a type IV phosphodiesterase inhibitor, has multiple anti-inflammatory effects including inhibition of TNF-alpha synthesis. METHODS: We investigated the effects of rolipram in prevention and delayed treatment of crescentic glomerulonephritis in Wistar Kyoto rats. Glomerulonephritis was induced by injection of nephrotoxic serum. RESULTS: In the preventive study, rolipram (6.25 mg/kg i.p. twice daily) was started 2.5 h before injection of nephrotoxic serum. Rolipram reduced the expression of TNF-alpha in glomeruli and renal tubules and abrogated glomerular injury on day 4 (99.7% reduction in albuminuria and 96.4% reduction in fibrin deposition). In the delayed-treatment experiment, rolipram was started 4 days after injection of nephrotoxic serum. Rolipram reduced renal excretion of TNF-alpha by 63% on day 7. TNF-alpha was not detected in the sera of treated or control rats. Delayed treatment was effective in crescentic glomerulonephritis, as shown by reduction in albuminuria by 38.1%, fibrin deposition by 60.8%, and crescent formation by 67% on day 7. CONCLUSIONS: Rolipram is effective both in prevention and treatment of experimental crescentic glomerulonephritis. This was associated with a reduction of renal production of TNF-alpha.

Animals↗
PubMed1999

Distinct chromosome 3 abnormalities in persistent polyclonal B-cell lymphocytosis.

Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare entity of unknown etiology characterized by a polyclonal expansion of B-lymphocytes with typical bilobulated forms, elevated serum IgM, and an additional isochromosome for the long arm of chromosome 3 as the sole change. In the present study, we investigated four cases of PPBL by means of conventional cytogenetic analysis and FISH. In all patients, the polyclonality of the lymphoproliferation was demonstrated by immunophenotypic studies, and PCR analysis failed to demonstrate clonal IGH rearrangements in three evaluated cases. In two patients, in addition to +i(3)(q10), banding techniques identified unrelated clones with trisomy 3. FISH studies using a chromosome 3 long arm-specific probe provided evidence that all cases had both +i(3)(q10) and +3. To determine more precisely the distribution of the chromosomal abnormalities within the peripheral lymphocyte population, we investigated two of these cases using a technique of simultaneous fluorescence immunophenotyping and interphase cytogenetics (FICTION). We demonstrated that both abnormalities were randomly distributed among the B-lymphocytes, independently of the kappa or lambda light chain isotype and the nuclear aspect. These data lead us to conclude that trisomy 3 represents, in addition to +i(3)(q10), another recurrent cytogenetic change in PPBL, suggesting that this lymphoproliferative disorder is associated with an increased frequency of chromosome 3 instability.

Adult↗
PubMed1999

Laboratory data in healthy volunteers: reference values, reference changes, screening and laboratory adverse event limits in Phase I clinical trials.

OBJECTIVE: Laboratory data are key evaluation procedures for Phase I clinical pharmacology for two reasons. Firstly, laboratory data are used within the screening process to exclude subjects with asymptomatic diseases, which could result in increased danger to themselves or confuse interpretation of the study results. Secondly, during study implementation, safety evaluation and in particular maximum tolerated dose determination have to be done by a case-by-case analysis, sometimes using laboratory adverse events (LAEs). Thus, relevant limits are needed to discriminate between a usual common variation and a significant abnormality, which is considered to be a LAE. This report presents laboratory data distribution, reference values and reference changes and, based on previously published new methods, suggests inclusion limits at screening and laboratory adverse event limits for analysis during study implementation. SUBJECTS AND METHODS: Nine hundred and twenty-seven young healthy male volunteers were recruited in one centre (Association de Recherche Thérapeutique). A standard screening process was carried out. Protocols were approved by the local ethics committee. Blood sampling was performed in the same conditions. Reference values (at screening and at baseline) were determined by a non-parametric procedure selecting 2.5% and 97.5% of the distribution of data. Reference changes were also defined as the 2.5-97.5% interval of distribution of the variations between the end of treatment and baseline. Inclusion limit and LAE limit methods of determination used had been specified in previous articles. RESULTS: Detailed results of laboratory data distribution, reference values at screening and at baseline, reference changes, inclusion limits and LAE limits are presented in tables with number of subjects, mean, median, standard deviation, minimal and maximal values and the 2.5-97.5% interval for each laboratory parameter. CONCLUSION: The key aims of this paper are to provide clinical pharmacologists with data, reference values or changes obtained in the real conditions of Phase I study implementation, and to propose relevant limits, either for screening as inclusion limits, or during studies as LAE limits. Thus, these data, reference values and specific limits improve the capacity to screen healthy volunteers and to analyse LAEs during Phase I studies.

Adult↗
PubMed1999

Translocations involving the short arm of chromosome 17 in chronic B-lymphoid disorders: frequent occurrence of dicentric rearrangements and possible association with adverse outcome.

Unbalanced translocations involving chromosome arm 17p, where the TP53 tumor suppressor gene localizes, are rarely described in chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL), but recent use of molecular cytogenetic techniques have indicated a significant incidence of TP53 deletions, suggesting the involvement of chromosome 17p in these disorders. By conventional karyotype, we have identified unbalanced translocations involving 17p in 14 out of 123 (11%) CLL/SLL patients with clonal abnormalities. Cases were characterized by resistance to chemotherapy and a poor clinical outcome. The karyotypes presented a high incidence of complex rearrangements and 17p translocations were characterized by various partners. In 10 cases a centric fusion was assessed by fluorescent in situ hybridization (FISH) experiments using specific centromeric probes. The incidence of dicentric translocations in these series is therefore significantly higher than usually described, arising in up to 71% (10 out of 14 cases). In all cases, translocations led to a monosomy 17p and to a TP53 monoallelic deletion. The adverse clinical outcome confirms that structural abnormalities involving chromosome 17p are associated with disease progression in patients with chronic lymphoproliferative disorders.

Antineoplastic Agents↗
PubMed1999

Reduced parathyroid functional mass after successful kidney transplantation.

BACKGROUND: Chronic uremia is responsible for secondary hyperparathyroidism (HPT II). Parathyroid secretion usually tends to normalize after kidney transplantation (KT), but the parameters of the reversibility of HPT II remain poorly defined, particularly the intrinsic mechanisms underlying the improvement of parathyroid function. METHODS: The kinetic functional parameters of the ionized calcium (iCa)/parathormone (PTH) relationship curve were studied in 11 patients with mild to moderate HPT II one and six months after successful KT. Hypercalcemia and hypocalcemia were induced, respectively, by CaCl2 and Na2-ethylenediaminetetraacetic acid (Na2-EDTA) infusions. RESULTS: The mean glomerular filtration rate remained stable during follow-up. Basal PTH decreased from 195 +/- 54 pg/ml before KT to 70 +/- 12 pg/ml six months later (P < 0. 005). During the tests, mean PTH levels decreased significantly between the two measured times for all iCa levels, indicating an improved parathyroid function. An analysis of the kinetic parameters of the curves showed significant decreases of the mean maximal and minimal PTH levels, respectively, from 340 +/- 91 to 220 +/- 30 pg/ml (P = 0.03) and from 25 +/- 6 to 15 +/- 5 pg/ml (P = 0.005). On the other hand, no change was noted in the parathyroid-cell calcium-sensitivity parameters (slope, set point) assessed using two different approaches, either the entire curve or the limited calcium-mediated suppression curve. CONCLUSION: Improvement of the parathyroid function between the first and sixth months post-KT seems mainly attributable to a reduction of the parathyroid functional mass.

Adult↗
PubMed1999

Development of scarring and renal failure in a rat model of crescentic glomerulonephritis.

BACKGROUND: The aim of this study was to develop and characterize a rat model of crescentic glomerulonephritis which progresses to glomerulosclerosis and renal failure. METHODS: Glomerulonephritis was induced in Wistar Kyoto rats by a single injection of rabbit anti-glomerular basement membrane antiserum. Albuminuria and serum creatinine were monitored. Kidneys were examined, from 2.5 h to 44 days, using light-microscopy and immunohistochemistry. To characterize the glomerular inflammatory infiltrate, glomeruli were digested to single cells and analysed by fluorescence-activated cell sorter (FACS) and by immunohistochemistry on cytospins. RESULTS: Rats developed albuminuria by 4 days and increased serum creatinine by day 18. Histology showed glomerular fibrinoid necrosis by day 4 and cellular crescents in a mean of 63% of glomeruli by day 11. By 6 weeks, rats had developed renal failure (mean creatinine >300 micromol/l) with 94% of the glomeruli showing glomerulosclerosis. The kidneys were also affected by severe interstitial nephritis and tubular loss. The glomeruli were infiltrated by monocytes/ macrophages (ED1+) and CD8+ (OX8+) cells. FACS analysis showed that CD8+ cells did not express T-cell markers (CD3, TCRalphabeta or TCRgammadelta) or the NK-cell marker (NKR-P1). FACS analysis of peripheral blood mononuclear cells demonstrated a population of monocytes reactive with OX8, and double-labelling of cytospin preparations of glomerular digests showed that a proportion of the CD8+ cells were a subset of ED1+ monocyte/macrophages. CONCLUSIONS: We have characterized a reproducible model of crescentic glomerulonephritis which rapidly progresses to chronic renal failure with glomerulosclerosis and tubulo-interstitial scarring. This model will be useful for testing new therapeutic approaches in crescentic glomerulonephritis.

Animals↗
PubMed1999

Value of captopril renal scintigraphy in hypertensive patients with renal failure.

UNLABELLED: The aims of this study were to show the value of captopril renal scintigraphy for detecting a renovascular cause in hypertensive patients with renal failure and to assess the ability to predict the beneficial effect of revascularization on renal function. METHODS: Thirty-eight patients with renal failure (mean glomerular filtration rate = 35 mL/min) underwent renal scintigraphy after injection of 99mTc-mercaptoacetyltriglycine. Baseline scintigraphy was performed, and the test was repeated 24 h later after oral administration of 50 mg captopril given 60 min before the test. RESULTS: In 5 of 6 patients with a renovascular cause for renal failure, and 2 of 3 patients with a probable arterial pathology, scintigraphy had a high probability. The result was indeterminate in the other 2 patients. In 5 of 11 patients with negative arteriography and 14 of 18 patients with probable absence of renovascular pathology, we found a low probability of functional renal artery stenosis. Six revascularization procedures were performed and were predictive of a beneficial effect in 5 patients. Time of peak activity was an effective predictor in each case. CONCLUSION: In hypertensive patients with renal failure, captopril renal scintigraphy can detect hemodynamic dysfunction downstream from a renal artery stenosis and can predict the beneficial effect of revascularization in some cases.

Adult↗