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Biomedical subjects

D Farge

Publications and source records attributed to D Farge.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of transplantation on the renin angiotensin system (RAS).

Hypertension in organ transplant recipients is associated with several functional modifications of the renin angiotensin system (RAS), which varies according to the type of transplanted organs (kidney, heart, liver or bone marrow) and the immunosuppressive regimen. Before transplantation, chronic organ failure is associated with direct and indirect stimulation of both systemic and local RASs. After transplantation, cyclosporin per se is the major determinant of hypertension. It induces stimulation of both systemic and local RAS via direct and indirect effects within the kidney and peripheral vessels. In kidney transplant recipients, ischaemia from the native kidneys and from the graft, due to acute or chronic rejection, also contributes to RAS stimulation. In cardiac transplant recipients, several haemodynamic parameters, abnormal cardiorenal neuroendocrine reflex mechanism and other hormonal systems (ANF, AVP, catecholamines) stimulate the RAS.

Humans↗
PubMed1997

Preclinical studies for cell transplantation: isolation of primate fetal hepatocytes, their cryopreservation, and efficient retroviral transduction.

Fetal hepatocytes are an attractive target for in utero cellular transplantation. Their use could provide a very efficient way for implanting normal or transduced cells into the livers of affected fetuses. Marking cells with recombinant retroviruses is a powerful tool for evaluating the chimerism of grafted animals. The technique relies on the ex vivo transduction efficiency of the engrafted cells. We have isolated fetal primary hepatocytes from nonhuman primates. The cells were cultured and transduced with a retroviral vector carrying the Escherichia coli beta-galactosidase gene. Optimal gene transfer efficiency was obtained 48-60 hr after plating and was as high as 90%. Cryopreservation had little effect on cell viability and infectivity: The viability of thawed hepatocytes remained high (75-85%) and the infection efficiency was identical to that of freshly isolated cells. Efficient ex vivo retroviral gene transfer into fetal hepatocytes provides an appropriate system for testing allogenic grafting and for modifying immunogenicity of engrafted cells. These results open up new perspectives for cell transplantation through cell banking.

Animals↗
PubMed1997

Osteopontin is associated with bioprosthetic heart valve calcification in humans.

Calcification of non-osseous tissues such as heart valves or vessels is a major concern in clinical practice. The exact mechanism is still unknown. Numerous studies have shown that mineral deposits of crystalline hydroxyapatite within these tissues were associated with increased non-collagenous protein content. More recently osteopontin was found to be associated with calcification in living tissues such as vessels and native human aortic valves. The aim of this study was to determine whether or not non-collagenous proteins can also be found in non-living tissues such as glutaraldehyde-pretreated porcine valves after implantation in humans. Thirty-eight glutaraldehyde pretreated porcine bioprostheses were studied: 16 not implanted and 22 after 11 years of implantation in the aortic and mitral valve position in humans. In areas of calcification vizualized by Von Kossa staining and microradiography, immunostaining using polyclonal antibodies against calcium-binding proteins showed osteopontin positive staining and no staining for osteocalcin, bone sialoprotein or osteonectin. In uncalcified areas and in non-implanted values, staining for osteopontin or other calcium-binding proteins was negative. Western blot analysis of macroscopically calcified and uncalcified areas showed that several proteins were adsorbed in implanted values and confirmed the presence of osteopontin in the calcified areas, while no immunolabelling was found in non-calcified areas, in uncalcified valves and in non-implanted valves. Thus the presence of osteopontin in the calcified areas of bioprosthetic heart valves implanted in human indicates that this protein is associated with bioprosthetic valvular calcification. Since these values are made of non-living connective tissue, and no cell immunostained for osteopontin was found around the calcified area, this suggests that a non-cellular mediated mechanism involving protein adsorption may play a role in bioprosthetic valvular calcification.

Bioprosthesis↗
PubMed1996

[Pregnancy after organ transplantation].

In the past twenty years, the increased number of organ transplant recipients and better immunosuppressive regims have enhanced transplant survival, and several transplant recipients may conceive pregnancy or paternity after the graft. There is no French registry of posttransplant pregnancies, but analysis of the international literature reports 2300 pregnancies after kidney transplantation, 100 pregnancies after heart and 3 after heart-lung transplantation, 90 pregnancies after liver transplantation. Paternity after the graft may occur with no increased incidence of malformations, nor teratogenic and immunosuppressive effects due to the therapeutic regimen. All pregnancies after transplantation have to be considered at high risk, underlying the need for simultaneous follow-up by the gyneco-obstetrical team for the baby and the pregnancy and by the transplant team for the graft and the mother. Outcome is generally excellent for the mother and the baby. However, transplant recipients with either high blood pressure, diabetes, serum creatinine above 160 mumol/l or within less than 1 year after the graft should be considered at too high risk to conceive a pregnancy with no deleterious effect on the mother and/or on the foetus.

Embryonic and Fetal Development↗
PubMed1996

[New and resurgent infectious diseases associated with poverty].

The economic crisis has led to the onset of resurgence of several infectious diseases among patients with social deprivation. Health access being difficult for these patients, delay between onset of symptoms and time of diagnosis is increased and therapeutic adherence is impaired. Such conditions favour the transmission of infectious agents via either direct human interaction (sexual and blood transmission) or arthropode-borne agents. Tuberculosis remains the most frequent infection observed in this population and appears as a major public health problem. Such diseases underline the need for global approach of the patient, including a search for infected contact of sufficient duration, treatments and prevention of recurrence.

Communicable Diseases↗
PubMed1996

Hepatocyte growth factor expressed by a retrovirus-producing cell line enhances retroviral transduction of primary hepatocytes: implications for in vivo gene transfer.

Hepatocyte Growth Factor (HGF) is the more potent mitogen of mature hepatocytes. We have examined the effect of human HGF expression by a recombinant retroviral cell line (MFG-LacZ) on retroviral transduction of primary mouse and human hepatocytes. The HGF in the supernatant of MFG-LacZ cell line was correctly processed and biologically active. Transduction of mouse and human hepatocytes with the supernatant of transfected cells was increased 5-fold, as determined by beta-galactosidase activity. The production of HGF was stable and did not interfere with the viral titers of the producer cells. This study provides evidence that expression of HGF within a retrovirus-producer cell line increases the transduction rate of primary hepatocytes. Since the number of corrected cells is a limiting step for phenotypic correction of liver deficiencies, our approach should improve hepatic gene therapy efficiency. Furthermore this cell line should be useful for in vivo liver gene therapy.

Animals↗
PubMed1996

[Classical anticoagulant treatment of venous thromboembolic disease in cancer patients. Apropos of a retrospective study of 71 patients].

In order to evaluate the efficiency of classical anticoagulant therapy for venous thromboembolic disease in cancer patients, we retrospectively analysed 71 patients treated with intravenous heparin first and then with antivitamin K. After a mean follow-up of 185 +/- 25 days, 23 patients (33%) were dead; nine patients (12%) had suffered from major haemorrhagic complications, which were not fatal, four of which were due to heparin overdosage; 17 patients (24%) showed recurrent venous thromboembolic disease. According to univariate statistical analysis, risk of major bleeding was not associated with the presence of either thrombocytopenia, abnormal blood coagulation, metastases and/or any other hemorrhagic risk factors; recurrence of venous thromboembolic disease was not associated with the presence of other risk factors for venous thromboembolic disease, nor with the presence or absence of metastases and/or of ongoing chemotherapy. Such results suggest that classical anticoagulant therapy for venous thromboembolic disease in cancer patients is neither effective nor safe. The present retrospective study underlines needs for further prospective analyses in order to evaluate potential benefit from other therapeutic strategies, such as use of low molecular weight heparins and/or vena cava filter placement.

4-Hydroxycoumarins↗
PubMed1996

Colonic ischemia reveals thromboangiitis obliterans (Buerger's disease).

Two years before the appearance of distal peripheral manifestations of thromboangiitis obliterans (Buerger's disease), a young man had acute peritonitis attributable to an ischemic perforation of the sigmoid colon. Only the histological examination of excised tissue was able to differentially diagnose this entity unambiguously.

Adult↗
PubMed1996

Proteins and bioprosthetic calcification in the rat model.

BACKGROUND AND AIM OF THE STUDY: The mechanism of valvular bioprostheses calcification is still unknown, but early studies showed increased Gla-protein content in calcified valves. Using an experimental model, which reproduces the clinical process, we therefore analyzed the role of minerals and proteins in bioprosthetic valvular calcification. METHODS: Glutaraldehyde pretreated porcine valves were studied before and after implantation in rats by X-ray, calcium (Ca) and phosphorus (P) measurement, Fourier Transform Infrared (FTIR) spectroscopy, SDS-PAGE and 45Ca ligand blotting of the extracted proteins. RESULTS: Before implantation, there was no X-ray calcification with very little Ca and P content. After implantation, X-ray calcifications appeared on day seven with increased Ca and P up to day 35 (p < 0.05, ANOVA). FTIR revealed structural proteins alone before implantation, plus minor proportions of lipids on day two, which always preceded Ca and P appearance. Ca and P increased up to day 35, first as amorphous and changed in carbapatite over time. SDS-PAGE before implantation revealed two proteins (66-kD and 54-kD) alone, which were sustained up to day 35. The 66-kD had 45Ca affinity. On day two, many other proteins appeared on SDS-PAGE, four of which (52, 45, 14 and below 14-kD) with 45Ca affinity. Protein pattern did not change from day two to 35. CONCLUSIONS: Valvular bioprosthesis calcification is associated with progressive increase in Ca and P content and at least five calcium-binding proteins: one intrinsic valvular protein, pre-existing to implantation, plus four other, extrinsic valvular proteins adsorbed within the tissue after implantation.

Animals↗
PubMed1996

Raynaud's phenomenon and digital necrosis induced by interferon-alpha.

We report two patients treated with interferon-alpha who developed Raynaud's phenomenon followed by multiple digital necrosis. Arteriography of the legs revealed diffuse distal narrowing. Histological examination of the resected tissue showed ischaemic necrosis within the dermis and subcutaneous tissue without vasculitis. Resolution of the symptoms was observed when interferon-alpha was withdrawn. Since other causes of Raynaud's phenomenon and digital necrosis were ruled out, a drug cause is likely. Raynaud's phenomenon should be looked for in patients treated with interferon-alpha. If present, immediate withdrawal of the drug is required.

Antineoplastic Agents↗
PubMed1995

Interactions between hemodynamic and hormonal modifications during PEEP-induced antidiuresis and antinatriuresis.

The interactions between hemodynamic and hormonal modifications during antidiuresis and antinatriuresis induced by positive end-expiratory pressure (PEEP) were studied in six patients under 15 cm H2O PEEP before PEEP and after the addition of lower body positive pressure (LBPP) to PEEP (PEEP+LBPP). We measured or calculated the following: cardiac index, systemic arterial, right atrial, pulmonary arterial, and pulmonary artery occlusive pressures; indexed renal blood flow (iodohippurate 131 sodium clearance); total blood volume (chromium 51 radiolabeled RBCs); glomerular filtration rate; urinary output; fractional excretion of sodium (FE Na+); plasma concentrations of antidiuretic hormone (ADH), plasma renin activity (PRA), norepinephrine and epinephrine; urinary concentration of PGE2 (PGE2u). Although LBPP application corrected PEEP deleterious effects on systemic and renal hemodynamics, sustained fall in Vu and in FE Na+ were observed. Antidiuresis was not due to ADH release. Sympathetic activation and high PRA appeared the main determinants of renal function alterations in PEEP ventilation.

Adult↗
PubMed1995

Activation of Moloney murine leukemia virus LTR enhances the titer of recombinant retrovirus in psi CRIP packaging cells.

The critical physiological function of the long terminal repeat in Moloney murine leukemia virus (MoMLV) gene expression has been thoroughly explored and shown to include binding sites for ubiquitous and tissue-specific transcription factors, such as the glucocorticoid responsive element (GRE) and the LVb sequence recognized by phorbol 12-myristate 13-acetate (TPA)-induced factors. The present study was undertaken to determine the effect of different activators, known to enhance expression of MoMLV, on their ability to modulate retroviral transcripts in psi CRIP producing cell lines. Improvement of recombinant retrovirus production by two psi CRIP producer cells was tested by using dexamethasone, TPA and sodium butyrate (Na-But) alone or in combination. We demonstrate that 5 mM Na-But, or 5 mM Na-But plus 1 microM dexamethasone significantly enhanced viral production. These compounds could induce a 10-fold increase in viral production. There was also a good correlation between the increased viral production and the titer measured after transduction of NIH 3T3. This improvement is of general interest, since a major goal for gene therapy is the production of high retroviral titer for increased transduction efficiency.

3T3 Cells↗
PubMed1995

[Chemotherapy and cardiotoxicity].

Among the various anticancer drugs, used alone or in combination during courses of chemotherapy, anthracyclines (leader: doxorubicin) are responsible for direct myocardial toxicity, which can exceptionally be acute, but more often chronic with a delayed onset. This cardiotoxicity is directly proportional to the cumulative dose administered and the recommended total dose for doxorubicin is 550 mg/m2. The risk factors able to potentiate cardiotoxicity must be analysed before starting chemotherapy and follow-up by ultrasonography and/or isotope ejection fraction must be repeated before each course. The treatment of anthracycline-induced heart failure consists of digitalis alkaloids combined with angiotensin converting enzyme inhibitors. The cardiac toxicity of 5FU is currently explained by the theory of coronary spasm, based on clinical findings such as chest pain associated with ischaemic electrical modifications. The incidence of this toxicity is low, but it can be fatal. Exceptional examples include the cardiotoxicity induced by high-dose cyclophosphamide responsible for acute haemorrhagic myocarditis, potentiation of the cardiotoxic effect of anthracyclines by dacarbazine and plicamycin, and serious ventricular and supraventricular arrhythmias induced by amsacrine. Among the various cytokines used in oncology, interferon is responsible for heart failure, reversible after stopping treatment, but also for ventricular arrhythmias, or even sudden death, the pathophysiology of which still remains unclear.

Antibiotics, Antineoplastic↗