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P Moreau

Publications and source records attributed to P Moreau.

At least 145 records · Page 8Linked to original sources
PubMed1996

Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery.

Aging is an important determinant of vascular disease. Endothelium-derived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function. This study was designed to directly measure effects of prolonged aging on endotheliai NO release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used. Blood pressure and plasma estradiol-17beta (E2) remained unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 micromol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor. In vessels suspended in organ chambers isometric tension was recorded. In the aorta, the initial rate of NO release and peak NO concentration were reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6). Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10(-10) - 10(-5) mol/liter) were also reduced in aortas from old as compared with young rats (n = 6, P < 0.05). The initial rate of NO release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r - 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, however, the initial rate of NO release as well as peak NO concentration did not decrease with age (n = 6 for each age group, NS). In both blood vessels, the NO release was unaffected by superoxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than in the pulmonary artery may be the cause. This appears important as NO plays a protective role by preventing vasoconstriction, thrombosis and atherosclerosis.

Aging↗
PubMed1996

Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study.

A phase III prospective randomized multicenter study was performed to determine whether quinine could improve the response rate of poor-risk acute leukemias (ALs) to standard chemotherapy including a multidrug resistance (MDR)-related cytotoxic agent. The rationale of the study was based on the negative prognostic value of MDR phenotype in ALs and the ability of quinine to reverse this phenotype both in vitro and ex vivo. Three hundred fifteen patients (median age, 49 years; range, 16 to 65) with relapsed (n = 108) or refractory (n = 32) acute myeloblastic leukemia (AML), relapsed (n = 27) or refractory (n = 9) acute lymphoblastic leukemia (ALL), secondary AL (n = 22) or blastic transformation of myelodysplastic syndrome ([MDS] n = 74) or myeloproliferative syndrome ([MPS] n = 43) were randomly assigned to receive mitoxantrone ([MXN] 12 mg/m2/d, days 2 to 5) and cytarabine ([Ara-C] 1 g/m2/12 h, days 1 to 5) alone or in combination with quinine (30 mg/kg/d, days 1 to 5; continuous intravenous infusion beginning 24 hours before MXN infusion). Side effects of quinine were observed in 56 of 161 quinine-treated patients and disappeared in all but four cases after one or two 20% dose decreases. Sera from quinine-treated patients showed increased MXN uptake in an MDR-positive cell line compared with matched sera obtained before quinine infusion. Quinine induced a significant increase in the incidence of nausea, vomiting, mucositis, and cardiac toxicity. A complete response (CR) was observed in 85 of 161 patients (52.8%) from the quinine-treated group versus 70 of 154 patients (45.5%) in the control group (P = .19). The most important differences between quinine and control group CR rates were observed in patients with refractory AMLs and blastic transformation of MDS and MPS. The CR rate was higher in P-glycoprotein-positive cases, although the difference was not significant. Failure of the regimen due to blastic persistence or blast number increase was higher in the control group (61 of 154 patients) than in the quinine group (45 of 161, P = .04). Early death was observed in eight cases (four in each arm) and death in aplasia in 27 cases (20 in quinine group v seven in control group, P = .01). The significant increase of toxicity in the quinine arm could have masked the clinical benefit of MDR reversion in poor-risk ALs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[Fusaria infection in patients with neutropenia: apropos of 3 cases].

The authors report three cases of fusarial infection in neutropenic patients with hematologic malignancies. The first patient was affected by a cutaneous extensive fusariosis. The second patient developed a fusarial lung infection during a multiple organ failure following allogenic bone marrow transplantation. The third patient who presented with refractory acute myelogenous leukemia, developed fusarial skin lesions, and died from pulmonary failure. The treatment of fusarial infection is disappointing and requires amphotericin B, in association with hematopoietic growth factors. The role of new agents, or combination chemotherapy remains to be determinated. The recovery of adequate neutrophil levels is the most important factor in the resolution of fusarial infection.

Adult↗
PubMed1996

[Primary granulocytic sarcoma of the pancreas: efficacy of early treatment with intensive chemotherapy].

In the absence of systemic chemotherapy after the diagnosis of primary granulocytic sarcoma (PGS), all patients will subsequently develop acute myelogenous leukemia (AML). The authors describe a case of PGS of the head of the pancreas found at laparotomy in a 32-year-old man. The patient received early after surgery, two courses of high-dose chemotherapy and, with a follow-up of 2 years, never developed AML. This rare observation illustrates the necessity of further early systemic chemotherapy after surgical excision of PGS.

Adult↗
PubMed1996

G-CSF alone mobilizes sufficient peripheral blood CD34+ cells for positive selection in newly diagnosed patients with myeloma.

We have evaluated CD34+ cell positive selection from granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) in 26 patients with either multiple myeloma (MM, n = 18) or follicular non-Hodgkin's lymphoma (NHL, n = 8). 26 PBPC were collected with two leukaphereses: 16 contained sufficient numbers of CD34+ cells and were elected. The absolute number of CD34+ cells in the leukapheresis products was found to be significantly related to the duration of underlying disease and exposure to prior treatment. CD34+ cell positive selection allowed recovery of a median of 35% of CD34+ cells, the selected fraction containing a median number of 1.43 x 10(6)/kg CD34+ cells/kg (range 0.48-41.5). 10 patients were transplanted and received a median dose of 1.51 x 10(6) CD34+ cells (range 0.48-4.2). The median time to granulocyte ( > 0.5 x 10(9)/l) and platelet ( > 20 x 10(9)/l) engraftment was 12 and 13 d respectively (ranges 10-13 and 0-95). Lymphoma cells were found by a sensitive polymerase chain reaction technique in four out of five CD34+ cell fractions tested.

Adult↗
PubMed1996

A pilot study of 220 mg/m2 melphalan followed by autologous stem cell transplantation in patients with advanced haematological malignancies: pharmacokinetics and toxicity.

We studied the pharmacokinetics and toxicity of 220 mg/m2 melphalan (HDM 220) followed by autologous stem cell transplantation in 16 patients with advanced haematological malignancies. Pharmacokinetic parameters (mean values of steady-state volume of distribution 14.6 l/m2, total body clearance 313 ml/min/m2, elimination half-life 46 min) were the same as those of 140 or 200 mg/m2 melphalan in previous reports. HDM 220 was feasible. Extramedullary toxicity was mainly W.H.O. grade 4 mucositis (13/16 patients). The median duration of 41 d (10, not reached) of thrombocytopenia < 25 x 10(9)/l was long. In multiple myeloma the response rate was 89% in heavily pretreated patients, suggesting that HDM 220 could be considered earlier in the course of the disease as an alternative consolidation therapy.

Adolescent↗
PubMed1996

Effect of endothelin antagonists on the responses to prostanoid endothelium-derived contracting factor.

1. The effect of endothelin antagonists on endothelium-dependent contractions was studied in conditions of stimulated endothelium-derived contracting factor (EDCF) release and with exogenous activation of thromboxane A2-endoperoxide receptors in the rat aorta. 2. The incubation of aortic rings with N omega-nitro-L-arginine methyl ester (L-NAME) led to EDCF-mediated contraction upon stimulation with acetylcholine (24 +/- 3% of KCl contraction). When vessels were preincubated with bosentan, an endothelinA- and endothelinB-receptor antagonist, in addition to L-NAME, acetylcholine-induced contraction was reduced to 8 +/- 2% (P < 0.01) of KCl contractions. PD147953, a selective endothelinA-receptor antagonist, reduced the contraction to 14 +/- 4% (P < 0.05) of KCl contractions. 3. Bosentan preincubation produced a significant parallel rightward shift of the contractions to U46619, a selective thromboxane A2 receptor agonist. In contrast, PD147953 failed to exhibit any inhibitory effect on U46619 contractions. 4. These results suggest that endothelin antagonists inhibit EDCF-mediated contractions by blocking endothelinA receptors and that, in addition, bosentan antagonizes the direct stimulation of thromboxane A2 receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Antihypertensive therapy prevents endothelial dysfunction in chronic nitric oxide deficiency. Effect of verapamil and trandolapril.

The objective of this study was to examine the effects of long-term antihypertensive therapy on blood pressure and vascular responses of resistance arteries during prolonged inhibition of nitric oxide synthesis. Four groups of 6-week-old Wistar-Kyoto rats were treated with either placebo as controls or N omega-nitro-L-arginine methyl ester (L-NAME) alone or in combination with verapamil or with trandolapril. Drugs were given orally for 6 weeks or short-term in vitro to vessels obtained from untreated rats. Endothelium-dependent and -independent relaxations as well as contractions were studied in isolated perfused mesenteric and renal arteries with an arteriograph. Kidney nitric oxide synthase activity was also evaluated. Verapamil and trandolapril prevented the increase in systolic blood pressure and the blunted acetylcholine-induced relaxations that occurred with L-NAME treatment without improving the nitric oxide synthase activity. Both antihypertensive regimens also normalized sensitivity to sodium nitroprusside, which was enhanced by L-NAME. In contrast, short-term in vitro preincubation with verapamil or trandolaprilat in the presence of L-NAME did not improve the impaired relaxations to acetylcholine. Long-term but not short-term therapy with a calcium antagonist or angiotensin-converting enzyme inhibitor improved the blunted endothelium-dependent relaxations in nitric oxide-deficient hypertension. These findings strongly suggest that the role of other vasodilator systems, which normally do not regulate vascular tone, is enhanced with long-term but not short-term treatment with these drugs. These observations emphasize the potential importance of these treatments in the management of hypertension in which nitric oxide production is diminished.

Animals↗
PubMed1996

Infradiaphragmatic Hodgkin's disease: long term results of combined modality therapy.

Hodgkin's disease (HD) confined below the diaphragm accounts for less than 5% of all patients with HD. Although the major characteristics of this presentation appear established, optimal modalities of treatment still remain difficult to define. From April 1972 to October 1988, 28 patients with newly diagnosed infra-diaphragmatic HD, clinical stages I or II have been treated with 3 successive prospective protocols combining initial chemotherapy and radiotherapy (40 gy). This series of patients accounted for 4,3% of patients with HD limited to clinical stages (CS) I and II. Overall survival and freedom from relapse at 15 years were 74,4% and 73% respectively, without significant differences between clinical stages I and II, presence or absence of B symptoms or histologic subtype. There is only a trend (p < 0,10) in favour of patients younger than 40 years. In all 7 clinically staged IA patients no relapses were seen and combined treatment does not appear to be better than inverted Y irradiation alone. On the other hand initial chemotherapy seems necessary in patients with CS II A and B since 15 of our 21 patients are alive in first CR whereas the crude rate of transdiaphragmatic nodal relapses may reach up to 53% following radiotherapy alone.

Adolescent↗
PubMed1996

[Post-transplantation of Hodgkin's disease. Clinico-pathologic study of 3 cases].

As a frequent complication of immunosuppression, lymphoproliferative disorders affect approximately 2 % of allorgan transplant recipients. Most of them are EBV-associated-B-cell-lymphoproliferations. Other types of non Hodgkin's lymphomas and Hodgkin's disease, as observed in general population, have only rarely been reported in this group of patients. We report three cases of Hodgkin's disease, which were diagnosed in two renal transplant recipients and one heart transplant patient. They were associated with Epstein-Barr virus, as demonstrated by immunohistochemistry and in situ hybridization. EBV is frequently associated with Hodgkin's disease in the general population, and always implicated in AIDS-related Hodgkin's disease. However in transplant patients the rarity of Hodgkin's disease argues against a direct oncogenic role of this virus.

Adult↗
PubMed1996

Successful allogeneic bone marrow transplantation for early relapse after autologous bone marrow transplantation in two cases of aggressive high-grade non-Hodgkin's lymphoma.

Two patients with high-grade disseminated non-Hodgkin's lymphoma relapsed 3 and 7 months respectively after high-dose chemotherapy and autologous BMT performed in first complete remission. Both patients had an HLA-identical sibling and received an allogeneic BMT 5 and 10 months after autologous BMT, after conditioning with fractionated 12 Gy total body irradiation plus cyclophosphamide. They both are alive and well, with a Karnofsky score of 100%, 15 and 27 months after allogeneic BMT. For selected patients with HLA-identical siblings and good performance status who relapse after autologous transplantation for high-grade non-Hodgkin's lymphoma, allogeneic BMT may be an option.

Adolescent↗
PubMed1996

[The Staca nail-plate in the treatment of trochanteric fractures].

PURPOSE OF THE STUDY: The Staca nail-plate (SNP) is 32 years old. This implant was created by Descamp and Kerner from Nice in 1964. This study evaluates the experience with the SNP in two Orthopaedic Departments from Metz and Nancy Regional Hospitals, between January 1989 and July 1991. MATERIAL AND METHODS: This is a clinical and radiological retrospective study. Out of the 175 patients, 152 were reviewed at 3 months and 127 at more than 9 months. The radiological assessment was made by measuring the post-operative cervical angle, the position of the nail within the femoral neck, the inter-fragmentary distance and the distance between nail and femoral head cartilage. 175 trochanteric fractures (119 women and 56 men) had osteosynthesis with the SNP. The mean age was 79 years (range: 36 to 96 years). Only 29 patients were free of general associated pathology. The fracture was always traumatic. The right femur was involved in 97 cases. Following the Ender classification there were 87 stable and 88 unstable fractures (59 complex pertrochanteric, 19 inter and sub-trochanteric and trochantero-diaphyseal). RESULTS: Post-operative reduction was anatomical in 66 per cent and satisfactory in 89 per cent of cases. In three cases there was an acetabular protrusion of the nail, in two cases there was a varus reduction and fixation and in six cases the plate was not fitting correctly the diaphysis. The average per-operative blood-loss was 300 cc. There was one per-operative death and eight early post-operative deaths. Sitting was allowed 24 hrs, after surgery in 94 per cent of patients. 68 per cent of patients started walking within the first 15 days after surgery. There were 37 per cent general complications, mainly respiratory and urinary infections, but also 2 deep-vein phlebitis, with pulmonary embolism and death. 17 post-operative hematoma were noted, out of which two required surgery. The general mortality reached 15 per cent in three months and 22 per cent in nine months. 70 per cent of the patients were free of pain at 3 months and 78 per cent at 9 months, 65 per cent being able to walk without crutches. Nail acetabular protrusion was observed in 16 cases (3 in early post-operative period, 8 within three months and 2 between the third and the ninth month). The protrusion was related to the nail positioning in 11 out of the 16 cases. This complication required SNP removal in 7 cases, replacement of the SNP in 3 cases and total hip arthroplasty in two cases. Correct nail length assessment is the important step in order to avoid protrusion and has to take into account the interfragmentary distance after reduction (if any). A good per-operative nail impaction is mandatory. CONCLUSION: Compared to other implants (THS, DHS, Gamma-nail, Ender), the SNP gives comparable results and a stable fixation. The SNP is a reliable implant. The most common complication in our series is protrusion which required reintervention in 6.8 per cent of the cases. Currently we avoid this complication by a good per-operative nail impaction.

Adult↗
PubMed1996

The time window of apoptosis: a new component in the therapeutic strategy for cardiovascular remodeling.

APOPTOSIS AND EXPERIMENTAL HYPERTROPHY: Apoptosis (programmed cell death) is a physiological counterpart of cell replication with shared as well as specific pathways. Our initial studies have demonstrated increased apoptosis in the heart, kidney and brain of spontaneously hypertensive rats (SHR) and mice, persisting in cultured vascular smooth muscle cells. In these target organs of hypertension, programmed cell death paralleled the well known hypertrophy/hyperplasia. We also observed that the two processes can be dissociated in time, as in experimental hypertrophy of the heart induced by pressure overload. In this context, only a short-lived apoptotic window precedes the overt development of cardiac hypertrophy. EFFECTS IN HYPERTENSION: We now propose that a more prolonged apoptotic window is present in hypertension. Apoptosis seems to be significantly reduced during the first weeks of life in SHR, possibly contributing to the early cardiac hyperplasia. However, increased apoptosis is clearly evident thereafter throughout the development of hypertension and fades below the levels observed in normotensive animals after the age of 24 weeks. ANTIHYPERTENSIVE THERAPY AND APOPTOSIS: In addition to the apoptotic windows that suggest a dynamic regulation of this process in disease states, antihypertensive therapy with angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists and calcium channel blockers can also modify the contribution of apoptosis, independently of the blood pressure fall. We propose that the presence of apoptotic windows and the involvement of this biological process as a primary or secondary event in cardiovascular remodeling should be taken into account when designing innovative therapeutic approaches.

Animals↗
PubMed1995

Viridans streptococcal bacteraemia in patients with neutropenia.

Viridans streptococcal bacteraemia is frequent in neutropenic patients. 25 neutropenic patients with viridans streptococcal bacteraemia were compared with 64 control patients. Exposure to repeated chemotherapy or cytarabine were independent risk-factors for streptococcal bacteraemia. The use of carboxyureidopenicillins and a stay in laminar-airflow rooms were protective. In a further cohort study of 49 patients, oral streptococci with the same ribotype as blood isolates were recovered from all 7 bacteraemic patients. The oral cavity is a portal of entry for viridans streptococci bacteraemia in neutropenic patients, especially after oral mucosal damage induced by repeated chemotherapy.

Anti-Bacterial Agents↗