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Biomedical subjects

P Herve

Publications and source records attributed to P Herve.

At least 19 recordsLinked to original sources
PubMed2001

Pathobiology of pulmonary hypertension. The role of platelets and thrombosis.

With the rare exceptions of PAH associated with antiphospholipid antibodies, genetic platelet dysfunction, or inherited deficiencies of antithrombotic pathways, the thrombotic lesions are secondary, but frequently occurring, in most cases of primary or secondary PAH. Pulmonary arterial hypertension is associated with thrombotic lesions and persistent vasoconstriction and structural remodeling of PA. Activated platelets interact with the PA wall and may contribute to the functional and structural alterations of pulmonary vessels by releasing vasoactive factors and mitogenic mediators.

Animals↗
PubMed2001

Fetal vascular response to maternal deep-vein thrombosis and subsequent heparin therapy.

The fetal umbilical and cerebral Doppler changes were recorded in a 27-year-old primigravida referred at 38 weeks for the treatment of an iliofemoral vein thrombosis. On admission and in comparison to a previous Doppler assessment systematically performed during growth scan at 37 weeks, the umbilical resistance index (URI) demonstrated an increase of 19%, the cerebral resistance index (CRI) a reduction of 15% and the cerebral-umbilical (C/U) ratio a decrease of 29% reaching the lowest value of 1.05. Under intravenous heparin therapy, Doppler normalisation was observed within 1 week and the mother delivered a healthy, non-hypoxemic baby by caesarean section at 39 weeks and 2 days. This observation suggests that deep-vein thrombosis (DVT) may, in some cases, be responsible for transient fetal hypoxia. Moreover, treatment with intravenous heparin had a direct beneficial effect on the fetus as it improved placental hemodynamics and fetal oxygenation.

Cesarean Section↗
PubMed2000

Ganciclovir-sensitive acute graft-versus-host disease in mice receiving herpes simplex virus-thymidine kinase-expressing donor T cells in a bone marrow transplantation setting.

BACKGROUND: The use of donor T cells expressing the herpes simplex thymidine kinase (HSV-TK) gene followed by ganciclovir (GCV) treatment could allow for specific modulation of the alloreactivity occurring after bone marrow transplantation. We are presently exploring such an approach in a phase I clinical trial. METHODS: To examine the beneficial effect of administrating HSV-TK-expressing donor T lymphocytes +/- GCV treatment on acute graft-versus-host disease (aGVHD) control, irradiated Balb/c or C57BL/6 mice underwent transplantation with allogeneic bone marrow cells in conjunction with CD3+ allogeneic splenocytes from transgenic mice expressing an HSV-TK transgene. GCV treatment was initiated upon the occurrence of severe aGVHD. RESULTS: GCV treatment resulted in a 40-60% long-term survival rate of GVHD-free recipients having received HSV-TK-expressing T cells, whereas only 0-6% of mice survived without GCV treatment. Lethal aGVHD occurred in all the control animals having received non-HSV-TK-expressing T cells, irrespective of GCV treatment. CONCLUSION: Our results demonstrate that the administration of donor HSV-TK-expressing T cells to hematopoietic stem cell graft recipients followed by GCV treatment at the onset of severe aGVHD significantly reduces aGVHD-induced mortality and results in GVHD-free surviving recipients.

Animals↗
PubMed2000

The supply of blood products in 10 different systems or countries.

Countries vary greatly in their ability to produce their own blood products including albumin and IVIgG. Part of this variability depends on the supply of plasma within the country. As has been seen most recently in the UK, the quality of the plasma and its acceptability for plasma fractionation must also be considered. Therefore concerns regarding the quality of the plasma have been added to those regarding the quantity.Only a few countries are nationally self sufficient in plasma. This has a marked effect on blood product availability and therefore the ability to treat patients. Unlike most pharmaceuticals, the plasma fractionation industry must rely, for its raw products, on plasma obtained from blood donors. As such this puts it in a potentially compromised situation since neither the supply nor the quality of the raw material can be assured and both of those will vary with time. This paper reviews the processes through which blood products are made available in 10 different systems including: Canada, England, France, Italy, Norway Scotland, Sweden, Switzerland, South Africa and USA. A series of specific questions were posed and the responses received from the various coauthors and other respondents provide comparative data on blood product availability in different areas of the world.

Blood Banks↗
PubMed2000

Cost-effectiveness of CD34+ dose in peripheral blood progenitor cell transplantation for non-Hodgkin's lymphoma patients: a single centre study.

Intensive high-dose chemotherapy with peripheral blood progenitor cell (PBPC) transplantation is a common strategy for aggressive non-Hodgkin's lymphomas (NHL). A retrospective cost-effectiveness analysis of CD34+ cell dose was carried out. Between 1994 and 1998, 28 patients were included. Efficacy was measured by the length of aplasia. Data collection concerned the period from graft day until discharge from hospital, and the post-graft period until graft day +100. Patients transplanted using a cell dose greater than 5 x 106/kg were found to have a faster hematological recovery. Average length of post-graft hospitalization was shorter and fewer blood products were required for patients with more than 5 x 106/kg CD34+ cells transplanted. Hospitalization was the major cost driver. A large reduction in procedure cost was obtained with a CD34+ cell count higher than 5 x 106/kg (-US$2740, -11%). This difference was directly related to hospitalization (-US$860) and platelet units transfused (-US$1,340). A sensitivity analysis showed the robustness of results. Our findings indicated that a CD34+ cell dose higher than 5 x 106/kg was more cost-effective than a lower dose in NHL patients. The collection of 5 x 106/kg CD34+ cells appeared necessary to optimize the PBPC procedure.

Adult↗
PubMed2000

Endothelial nitric oxide synthase function in pig lung after chronic pulmonary artery obstruction.

Because long-term pulmonary artery (PA) obstruction is associated with expansion of the systemic blood supply to the lung, chronic ischemia may not occur, and endothelium nitric oxide synthase (eNOS) function may be preserved in postobstructive pulmonary arteries. To test this hypothesis, we studied piglets 2 d or 5 wk after left PA ligation or a sham operation. We measured left lung ATP and lactate lung concentrations; calcium-dependent and calcium-independent NOS activities and eNOS protein; and left PA relaxations in response to acetylcholine, calcium ionophore, and sodium nitroprusside. Decreases in ATP and increases in lactate concentrations were significantly attenuated after 5 wk PA occlusion (p < 0.05 versus sham and 2-d ligation). Compared with sham and 2-d PA occlusion, calcium-dependent NOS activity and eNOS protein were lower in the long-term PA occlusion group. Calcium-independent NOS activity was unchanged. Acetylcholine and calcium ionophore relaxations were impaired after 5 wk, whereas only acetylcholine relaxation was impaired after 2-d PA occlusion. Relaxation to sodium nitroprusside remained unchanged. In conclusion, despite relative conservation of lung energy metabolism, prolonged PA occlusion decreased eNOS function and protein in postobstructive pulmonary arteries.

Adenosine Triphosphate↗
PubMed1999

Pulmonary thromboendarterectomy for chronic thromboembolic obstruction of the pulmonary artery in piglets.

OBJECTIVE: The 2 main causes of death after thromboendarterectomy for chronic pulmonary thromboembolism are incomplete repermeabilization responsible for persistent pulmonary hypertension and acute high-permeability pulmonary edema. We wish to establish an experimental model of chronic pulmonary thromboembolism to replicate the conditions encountered during and after pulmonary thromboendarterectomy. METHODS: Multiple-curled coils and tissue adhesive were embolized in 6 piglets to induce complete obstruction of the left pulmonary artery, documented by angiography. After 5 weeks, the main pulmonary artery was repermeabilized by thromboendarterectomy during circulatory arrest. The left lung was reperfused ex vivo with autologous blood at constant flow, and patency of the pulmonary artery was evaluated on a barium angiogram. The endarterectomy-reperfusion procedure was also done in 6 nonembolized piglets that served as the controls. The severity of lung injury induced by 60 minutes of reperfusion was assessed on the basis of measurements of the lung filtration coefficient and of lung myeloperoxidase activity. RESULTS: Marked hypertrophy of the bronchial circulation was seen in the chronic pulmonary thromboembolism group. Thromboendarterectomy removed the organized obstructing thrombus that was incorporated into the arterial wall and restored patency of the pulmonary artery. Acute lung inflammation and high-permeability edema occurred after reperfusion, as indicated by a 1.5-fold increases in both lung filtration coefficient and lung myeloperoxidase values in the chronic pulmonary thromboembolism group; these 2 variables being correlated. CONCLUSIONS: Our model replicated the perioperative conditions of pulmonary thromboendarterectomy, suggesting that it may prove useful for improving the repermeabilization technique and for investigating the mechanisms and prevention of reperfusion injury.

Animals↗
PubMed1999

Vascular smooth muscle differentiation of murine stroma: a sequential model.

Previous studies by our group showed that stromal cells from human long-term marrow cultures were mesenchymal cells following a vascular smooth muscle pathway. The present study using 58 immortalized stromal lines from different hematopoietic sites was conducted to verify whether this hypothesis also held true for murine stroma. Principal components analysis performed using cytoskeletal and extracellular matrix proteins allowed the segregation of five factors explaining more than 70% of the variance. Factor I, including osteopontin and vimentin, and factor II, laminins and fibronectins, were representative of the mesenchyme. The remaining three factors were representative of vascular smooth muscle: factor III, including alphaSM actin, SM alpha actinin, SM22alpha, EDa+ fibronectin, and thrombospondin-1; factor IV, metavinculin and h-caldesmon; and factor V, smooth muscle myosin SM1 and desmin. All lines expressed factors I and II; 53 lines expressed factor III, 35 lines expressed factor IV; and 11 lines expressed factor V. A second principal components analysis including membrane antigens indicated the cosegregration of vascular cell adhesion molecule-1 with osteopontin and that of Ly6A/E with vimentin, whereas CD34 and Thy-1 appeared to be independent factors. The heterogeneity of vascular smooth muscle markers expression suggests that harmonious maintenance of hematopoiesis depends on the cooperation between different stromal cell clones.

Animals↗
PubMed1998

Prolonged remission and autologous recovery in two patients with chronic myelogenous leukemia after graft failure of allogeneic bone marrow transplantation.

Two patients with Philadelphia-positive chronic myelogenous leukemia underwent allogeneic bone marrow transplantation from a related HLA mismatched donor (patient 1) or from an unrelated HLA-identical donor (patient 2). Following bone marrow transplantation partial engraftment (patient 1) or graft failure (patient 2) occurred followed by autologous Philadelphia negative hematopoietic recovery either spontaneously (patient 1) or after infusion of autologous bone marrow rescue (patient 2). Neither Philadelphia chromosome, nor bcr-abl rearrangement was detectable by PCR analysis up to 7 years (patient 1) and 9 years (patient 2) post-transplantation. These two observations indicate that sustained engraftment of allogeneic bone marrow stem cells following a myeloablative regimen is not necessary to cure chronic myelogenous leukemia. It is hypothesized that the proliferative advantage of Philadelphia-negative progenitors and the anti-leukemic effect of lymphocytes in the graft have resulted in prolonged remission of the patients.

Adult↗
PubMed1998

Impaired renal graft survival after a positive B-cell flow-cytometry crossmatch.

BACKGROUND: The clinical and immunological relevance of a positive B-cell flow-cytometry (B-FCXM) crossmatch in renal transplantation is still controversial. METHODS: We retrospectively analysed 145 consecutive cadaveric renal transplantations performed from May 1991 to September 1995 in our institution. All grafts were transplanted following a negative IgG T-cell complement-dependent cytotoxicity crossmatch (T-CDCXM). Concomitantly to CDCXM, B-cell and T-cell FCXM were performed and results were expressed as a mean fluorescence index (FI). Two groups were compared: 116 recipients grafted with a negative B-FCXM vs a group of 19 patients grafted with a positive B-FCXM. RESULTS: The two groups were similar for length of cold ischaemia, donor and recipient's age and degree of HLA mismatching. The proportion of patients with pre-transplant anti-HLA class I antibodies or a retransplantation was significantly increased in the positive B-FCXM group vs the negative B-FCXM group. Recipient survival at 48 months was not significantly different in the two groups. However, graft survival at 12 and 48 months was significantly poorer in the positive B-FCXM than in negative B-FCXM (68% vs 90% at 12 months: P = 0.007, and 57% vs 79% at 48 months: P = 0.02). Within the positive B-FCXM group, no differences were found in pre-transplant anti-HLA class I or II alloimmunization as well as retransplantation frequency between the patients who lost their graft and the patients who did not. CONCLUSION: Our results suggest that a pretransplant positive B-FCXM is associated with an impaired long-term graft survival in renal allotransplantation.

Antibodies↗
PubMed1998

Lung reperfusion injury after chronic or acute unilateral pulmonary artery occlusion.

Because the lungs receive their blood supply from both the pulmonary and bronchial systems, chronic pulmonary artery obstruction does not necessarily result in severe ischemia. Ischemia-reperfusion (IR) lung injury may therefore be attenuated after long-term pulmonary artery obstruction. To test this hypothesis, isolated left lungs of pigs were reperfused two days (acute IR group) or 5 wk (chronic IR group) after left pulmonary artery ligation and compared to those of sham-operated animals. The severity of IR-lung injury after 60 min ex vivo reperfusion of the left lung was assessed based on lung histology and measurements of filtration coefficient (Kfc), pulmonary arterial resistance (Rpa), and lung myeloperoxidase (MPO) activity. Marked bronchial circulation hypertrophy was seen in the chronic IR group. Hemorrhagic alveolar edema was found in all acute IR lungs but not in sham or chronic IR lungs. Compared with the sham-operated controls, Kfc and Rpa increased two-fold and threefold, and MPO 1.5-fold and twofold in the chronic and acute IR groups, respectively. In conclusion, IR-induced lung injury was markedly reduced when it occurred 5 wk after pulmonary artery ligation, probably because the systemic blood supply to the lung had time to develop, limiting ischemia.

Animals↗
PubMed1998

Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension.

In a subset of patients with primary pulmonary hypertension (PPH), high doses of oral calcium-channel blockers (CCB) produce a sustained clinical and haemodynamic improvement. However, significant side-effects have been reported during acute testing with CCB. Therefore, to identify accurately patients who may benefit from long-term CCB therapy, there is a need for a safe, potent and short-acting vasodilator. The aim of this study was to compare the acute response to inhaled nitric oxide (NO) and oral high doses of CCB in 33 consecutive patients with PPH. A significant acute vasodilator response was defined by a fall in both mean pulmonary artery pressure and total pulmonary resistance by >20%. Ten patients responded acutely to NO, nine of whom responded acutely to CCB, without any complications. The 23 other patients failed to respond to NO and CCB. In these nonresponders, nine serious adverse events were observed with CCB (38%). There was no clinical or baseline haemodynamic feature predicting acute vasodilator response. Long-term oral treatment with CCB was restricted to the nine acute responders and a sustained clinical and haemodynamic improvement was observed in only six patients. In primary pulmonary hypertension, the acute response rate to high doses of calcium-channel blockers is low (27%). Serious adverse reactions to high doses of calcium-channel blockers during acute testing are frequently observed in nonresponders. It is concluded that nitric oxide may be used as a screening agent for safely identifying patients with primary pulmonary hypertension who respond acutely to calcium-channel blockers and may benefit from long-term treatment with these agents.

Administration, Inhalation↗
PubMed1997

Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM).

Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.

Acute Disease↗
PubMed1997

The broad spectrum of cytokine gene expression by myoid cells from the human marrow microenvironment.

Nontransformed stromal colony-derived cell lines (CDCLs) consist of a pure stromal cell population that differentiates following a vascular smooth muscle cell repertoire, and whose in vivo counterpart is that of myoid cells found in adult and fetal human bone marrow cords. We studied the cytokine expression by reverse-transcriptase polymerase chain reaction (RT-PCR) from pooled fast-growing clones from 10 different bone marrow samples. RT-PCR indicated that 30 cytokines (out of 42 studied) were expressed by CDCLs (20 after medium renewal and hydrocortisone renewal, three after addition of interleukin I beta (IL-1 beta) and seven in only part of the CDCL layers examined). The cytokines expressed comprised mediators known to be involved in the maintenance of early and late hematopoiesis (IL-1 alpha and IL-beta, IL-6, IL-7, IL-8, IL-11 and IL-13; colony-stimulating factors, thrombopoietin, erythropoietin, stem cell factor, fit 3-ligand, hepatocyte cell growth factor, tumor necrosis factor alpha, leukemia inhibitory factor, transforming growth factors beta 1 and beta 3; and macrophage inflammatory protein 1 alpha), angiogenic factors (fibroblast growth factors 1 and 2, vascular endothelial growth factor) and mediators whose usual target (and source) is the connective tissue-forming cells (platelet-derived growth factor A, epidermal growth factor, transforming growth factors alpha and beta 2, oncostatin M and insulin-like growth factor 1), or neuronal cells (nerve growth factor). The cytokines not expressed were lymphokines (IL-2, IL-3, IL-4, IL-5, IL-9, IL-10, and IL-12 and interferon gamma) or mediators synthesized by macrophages (inhibin, activin, platelet-derived growth factor B, and IL-1 receptor antagonist). This study complements the description of the phenotype of the myoid cells, confirming that these cells are the marrow connective tissue-forming cells; moreover, this work suggests that stromal control of hematopoiesis is multifactorial and that myoid cells are involved in the control of marrow angiogenesis and innervation.

Blotting, Western↗
PubMed1997

Fortuitous detection of uniparental isodisomy of chromosome 6.

Uniparental isodisomy is defined as the inheritance of two copies of the same parental chromosome and can result in defects when it produces homozygosity for a recessive mutation or in the presence of imprinting. We describe the detection of a chromosome 6 uniparental isodisomy in a 9 year old girl, discovered during a search for an HLA identical sib. HLA typing, erythrocyte phenotyping, and genotypes of microsatellite polymorphisms were compatible with a paternal isodisomy of chromosome 6, with normal biparental origin of the other chromosomes. Paternal cells were not responsive to the patient's cells in mixed lymphocyte cultures. This fortuitous detection of a chromosome 6 isodisomy suggests that cases of chromosome 6 UPD may not be deleterious and may therefore go undetected.

Cells, Cultured↗
PubMed1997

Production and consumption of the tetrapeptide AcSDKP, a negative regulator of hematopoietic stem cells, by hematopoietic microenvironmental cells.

This study was performed to evaluate the role of human microenvironmental cells in the metabolism of AcSDKP, a physiological inhibitor of hematopoietic stem cells. Using long-term marrow cultures (LTMCs), whose medium already contained a baseline value of AcSDKP, we found after 2 weeks a net output in the culture supernatant indicating that release by cells from the adherent layer was superior to consumption of the peptide. Since human microenvironmental cells consist of macrophages and vascular smooth-muscle-like stromal cells we generated pure populations of macrophages (by culturing cord blood cells in the presence of granulomonocytic colony-stimulating factor) and of stromal cells (generated by stromal colonies). We found in supernatants of macrophage cultures a significantly (p < 0.01) increased level of AcSDKP (compared with value in medium) while in supernatants of stromal cell cultures the level was decreased. Cell content of angiotensin-converting enzyme (ACE) in stromal cells was higher than in macrophages, which suggests a degradation of AcSDKP by stromal cells because of their higher amount of ACE. Finally, we analyzed the content of AcSDKP in adherent layers of LTMCs (with or without extracellular matrix [ECM] components), macrophages, and stromal cells. We found levels of AcSDKP of 1.5 pMol per 106 cells in extracts from macrophages or from stromal cells. On the contrary, extracts from primary layers of LTMCs contained 3 times more AcSDKP; however, after treatment of primary layers by collagenase, AcSDKP level fell to 1 pMol per 10(6) cells. Immunofluorescence using an anti-AcSDKP monoclonal antibody showed an extracellular network in certain areas of LTMCs. This study shows that 1) macrophages synthesize and release in the supernatant AcSDKP, 2) stromal cells probably degrade the peptide via ACE, and 3) components of the ECM from LTMCs serve as a reservoir for the peptide. These results are reminiscent of what has been described for growth factors, produced by microenvironmental cells, and stored in the ECM in close vicinity to hematopoietic precursors.

Adipose Tissue↗
PubMed1996

Evidence that a transient enhancement of endogenous hematopoiesis contributes significantly to the favorable outcome following interleukin 1 pretreatment and allogeneic bone marrow transplantation.

The administration of IL-1, a potent radioprotective cytokine, before allogeneic BMT is associated with an early transient increase of circulating granulocytes, successful engraftment, and accelerated multilineage hematopoietic recovery. We have examined the effects of IL-1 alpha pretreatment on the engraftment of an allogeneic BMT unable to sustain survival by itself after a lethal irradiation: (1) transplantation of a limited amount of marrow cells and (2) transplantation several days after irradiation. IL-1 was unable to allow the engraftment of an early quantitatively inadequate BMT. However, delayed BMT with limited amounts of marrow cells was associated with engraftment in IL-1 pretreated recipients. Engraftment of a late (day 12) BMT in these IL-1-pretreated mice was comparable to the engraftment of a similar day 12 allogeneic BMT in non-IL-1-pretreated mice rescued from the lethal irradiation by an early (day 1) syngeneic graft. These findings demonstrate that IL-1 pretreatment can result in a dissociation between BMT-induced survival and engraftment and suggest that the favorable effects of IL-1 pretreatment in an allogeneic BMT setting are mainly mediated through a transient enhancement of endogenous hematopoiesis and not through a direct effect on the allogeneic stem cells present in the marrow graft.

Animals↗