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D Farge

Publications and source records attributed to D Farge.

At least 19 recordsLinked to original sources
PubMed2001

Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease.

BACKGROUND: Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. METHODS: Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being <70% of the predicted value in 18/36 (50%). Pulmonary hypertension was described in 7/37 (19%) patients and renal disease in 5/37 (14%). The Scl-70 antibody was positive in 18/32 (56%) and the anticentromere antibody in 10% of evaluable patients. Peripheral blood stem cell mobilisation was performed with cyclophosphamide or granulocyte colony stimulating factor, alone or in combination. Thirty eight patients had ex vivo CD34 stem cell selection, with additional T cell depletion in seven. Seven conditioning regimens were used, but six of these used haemoimmunoablative doses of cyclophosphamide +/- anti-thymocyte globulin +/- total body irradiation. The median duration of follow up was 12 months (3-55). RESULTS: An improvement in skin score of >25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. CONCLUSION: Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.

Adolescent↗
PubMed2001

Diagnostic value of a nested polymerase chain reaction assay on peripheral blood mononuclear cells from patients with pulmonary and extra-pulmonary tuberculosis.

SETTING: Saint Louis Hospital, Paris, France. OBJECTIVE: To determine the clinical relevance of detection of Mycobacterium tuberculosis DNA by nested polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMCs) in the rapid diagnosis of tuberculosis. DESIGN: Single-centre prospective case study of 90 hospitalised patients and 50 healthy subjects or blood donors from 1 January to 30 June 1998. RESULTS: Twenty-three patients were diagnosed with tuberculosis (26.7%); 20 tuberculosis patients were culture-positive, with seven smear-positive for acid-fast bacilli. Sensitivity of smear, culture and nested PCR was 30.4 (7/23), 87 (20/23) and 30.4% (7/23), respectively. The specificity of smear and culture was 100%, and the specificity of the nested PCR was 96% in the healthy subjects. However, the specificity decreased to 83.6% in the hospitalised patients, with 11 nested PCR-positive patients without a diagnosis of tuberculosis. The sensitivity of the nested PCR was low in pulmonary tuberculosis (22.2%), but increased in pulmonary/extra-pulmonary tuberculosis (50%), extra-pulmonary tuberculosis (33%), and disseminated tuberculosis (33%). CONCLUSION: The use of a nested PCR assay on PBMC may pose problems for the rapid diagnosis of tuberculosis with regard to low sensitivity and specificity. However, further studies are needed to confirm this technique as an alternative test for the diagnosis of paucibacillary forms of tuberculosis.

Adult↗
PubMed2000

[Histoplasmosis due to Histoplasma capsulatum capsulatum and HIV infection].

PURPOSE: Histoplasmosis due to Histoplasma capsulatum is a granulomatous fungic infection which appears opportunistic and disseminated in immunocompromised patients, especially among HIV patients in whom it can lead to death. Histoplasmosis is endemic in numerous areas worldwide, but in Europe most of the cases reported are imported. We describe the clinical features and the available diagnosis methods issued from our experience in French Guyana. METHODS: Contamination occurs by inhalation of spores contained in dust. Most endemic areas are located on the American continent, including the French West Indies, where the incidence of histoplasmosis among HIV patients in French Guyana varies from 1.2 to 2.2% per year. In non-immunocompromised patients, histoplasmosis is asymptomatic most of the time. In HIV patients, the disseminated form is common and may occur many years after exposure to the fungus. RESULTS: Non-specific symptoms, similar to those of either tuberculosis or other opportunistic infections, may reveal disseminated histoplasmosis in patients with AIDS. Early treatment (amphotericin B or itraconazole) is effective; however, it should be followed by a lifelong antifungic treatment (itraconazole) to prevent relapse. CONCLUSION: The infection should be suspected in any febrile HIV-infected patient with CD4 blood cell count < 200/mm3, if he/she ever travelled in an endemic zone. Direct examination of smear relating to clinical symptoms help guide diagnosis, while culture will confirm it after at least 4 weeks. Efficient serologic techniques for HIV-infected patients are not available in Europe.

AIDS-Related Opportunistic Infections↗
PubMed1999

[Bone marrow transplantation in the treatment of autoimmune diseases. ISAMAIR Group].

EXPERIMENTAL BASIS AND CLINICAL OBSERVATIONS: Remission of an autoimmune disease has been observed in certain patients after bone marrow allograft from a healthy donor. Autoimmune disease in the donor can also be transmitted to an unaffected recipient. These phenomena would be hematopoietic-dependent. BONE MARROW ALLOGRAFTS: Indications for the treatment of refractory autoimmune diseases are exceptional due to the related mortality even in patients without malignant hematologic disease. A NEW THERAPEUTIC CONCEPT: Therapeutic intensification, followed with autologous peripheral stem cell grafts, a procedure with a mortality below 3% in 1997, constitutes a therapeutic alternative in these difficult indication concerning severe refractory autoimmune diseases including: sclerodermia, vasculitis, lupus, inflammatory myositis, autoimmune cyopenia.

Autoimmune Diseases↗
PubMed1999

Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Groupe Cooperatif de Transplantation d' Ile de France (GCIF).

BACKGROUND: The exact reasons for the high incidence of Kaposi's sarcoma (KS) after kidney transplantation are still unknown. Immunosuppression is classically considered as the main risk factor, but the relative risk contributed by the patient's geographic origin and by human herpes virus (HHV)-8 infection still has to be determined. METHODS: We carried out a retrospective and a prospective study among kidney transplant recipients (TP) to identify the risk factors for posttransplantation KS. Each of 30 KS patients was matched with two controls to investigate the association with geographic origin, immunosuppressive regimen, HHV-8 antibodies before and after transplantation, and other infections. Among TP with new onset of KS, we prospectively evaluated HHV-8 serology and viremia in response to decreased immunosuppression. RESULTS: African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/mm3 at the time of diagnosis and initial use of polyclonal antilymphocyte sera were risk factors for KS. After multivariate analysis, origin in Africa or Middle East and use of antilymphocyte sera for induction remained as independent risk factors. Sixty-eight percent (17/25) of TP with HHV-8 antibodies before or after transplantation developed KS compared with 3% (1/33) of seronegative TP (P<0.00001). HHV-8 DNA was detectable in seven of nine peripheral blood mononuclear cells (PBMC) and in six of six KS lesions at diagnosis; it became negative in PBMC in three of five patients in parallel with tumor regression. CONCLUSION: African and Middle East geographic origins, HHV-8 infection before and after kidney transplantation, and initial use of polyclonal antilymphocyte sera were independent risk factors for KS. The presence of HHV-8 antibodies before or after transplantation was highly predictive of the emergence of posttransplantation KS and conferred a 28-fold increased risk of KS (odds ratio=28.4; 95% confidence interval: 4.9-279). Detection of HHV-8 DNA within PBMC and KS lesions seems related to tumor burden and evolution.

Adult↗
PubMed1999

[Mitral papillary fibroelastoma in a HIV infected patient].

BACKGROUND: Papillary fibroelastoma of the endocardium is a benign cardiac tumor which may cause embolic events. CASE REPORT: We report the first case, to our knowledge, of cardiac papillary fibroelastoma which was revealed by cerebral ischemic events in a patient infected by the human immunodeficiency virus. The initial diagnosis was mitral endocarditis complicated by cerebral embolic events. DISCUSSION: This case demonstrates that fibroelastomas should be added to other valvular diseases described in HIV infected patients. We recall the embolic potential of cardiac papillary fibroelastomas which warrant surgical treatment.

Adult↗
PubMed1999

No evidence for a role of human herpesvirus type 8 in sarcoidosis: molecular and serological analysis.

The aim of this study was to analyse the association between human herpesvirus type 8 (HHV8) and sarcoidosis. Using nested polymerase chain reaction (PCR), we tested the presence of HHV8 DNA sequences in 13 skin specimens and peripheral blood mononuclear cells from eight patients suffering from sarcoidosis. We also looked for the presence of HHV8 antibodies in the sera of 28 patients with sarcoidosis using three techniques: two indirect immunofluorescence assays and an enzyme-linked immunosorbent assay with recombinant capsid protein fragment encoded by open-reading frame 65. HHV8 PCR analysis was negative while HHV8 serological studies showed an overall prevalence of 18% among patients suffering from sarcoidosis: 43% in patients from sub-Saharan Africa, 17% in patients from Northern Africa, 12.5% in patients from the French West Indies and 0% in French patients. In conclusion, our results do not indicate an association between HHV8 and sarcoidosis but reflect the seroepidemiology of this virus in different geographical regions.

Adult↗
PubMed1999

[Dermatologic consultation in a precarious situation: a prospective medical and social study at the Hôpital Saint-Louis in Paris].

INTRODUCTION: The aim of our study was to evaluate the outcomes and the cost of the dermatological consultation for poor and destitute patients, in Saint-Louis Hospital. PATIENTS AND METHODS: We carried out a prospective study from May to October 1996. One hundred and eighty-nine patients (237 consultations) who had no social welfare, were examined. RESULTS: They revealed that 82 p. 100 were male, 63.7 p. 100 were French, 13.9 p. 100 came from Maghreb, 9.7 p. 100 from Sub-Saharan Africa, 73 p. 100 were homeless and 25.7 p. 100 were alcoholic. The average age was around 37.6. The main medical disorders: scabies (56.5 p. 100), lice (22.4 p. 100) and cutaneous infections (7.2 p. 100) were related to the patients' living conditions and their social and economic situation. The other diseases observed were identical to the ones detected in regular health care centers. Complementary laboratories were necessary in 9.3 p. 100 consultations. Only 2 p. 100 of patients were admitted in Hospital. Local treatment was applied by nurses in 67 p. 100 of cases. Drugs were delivered free of charge by the Hospital's pharmacy in 64 p. 100 of cases. The cost of drugs was 83 FF per patient. The mean of duration of treatment was 10.5 days. DISCUSSION: Social workers are a key element in helping the patients to recover their social rights (49 p. 100 of patients have recovered social rights after 6 months). The frequency of skin diseases is higher in this population than in general population, especially in homeless persons. Access to health care is a problem of public health.

Adult↗
PubMed1998

Amphotropic retroviral vectors displaying hepatocyte growth factor-envelope fusion proteins improve transduction efficiency of primary hepatocytes.

The development of retroviral vectors with cell-specific targeting capabilities will be an important step toward successful in vitro gene therapy. This article describes the generation of a retroviral vector with enhanced binding abilities for cells bearing the c-Met receptor: the Madin-Darby canine kidney (MDCK) cell line and primary hepatocytes. The human hepatocyte growth factor (HGF) was displayed on murine amphotropic retroviral vectors by fusion to the viral transmembrane envelope glycoprotein (TM). The resulting chimeric envelope HGF-TM was expressed in an amphotropic packaging cell line producing viral particles that display both HGF-TM and the wild-type envelope. These modified viral particles had a titer equivalent to that of unmodified particles. Modified particles infected MDCK cells more efficiently than did unmodified amphotropic retrovirus. Adding anti-HGF antibodies to the viral vector particle supernatant prior to infection confirmed that the increased infection was mediated by the HGF moiety. The chimeric viruses also infected primary mouse and nonhuman primate fetal hepatocytes more effectively. Furthermore, these cells could be induced to proliferate by the modified HGF-TM viruses. Since exogenous HGF is primarily taken up by the liver, these results may have implications for retroviral vector design for liver-directed human gene therapy.

3T3 Cells↗
PubMed1998

Infrared spectroscopy in the evaluation of the process of calcification of valvular bioprostheses.

BACKGROUND: The methods currently used to analyze the process of calcification of bioprostheses give only global information on calcium deposition. We investigated the potential advantage of infrared spectroscopy, which makes it possible to analyze the various components of the calcification process, ie, lipids, proteins, and calcium deposits. METHODS: Sixty porcine aortic leaflets were fixed in 0.6% glutaraldehyde and then subsequently implanted in 10-day-old Wistar rats. The valve leaflets were removed 2, 7, 14, 21, 35, and 56 days after implantation. RESULTS: Before implantation infrared spectroscopic analysis revealed the presence of proteins only. On day 2 after implantation, all valves showed minor lipid deposits. On day 7, amorphous calcium phosphate was detected. Between days 7 and 14, crystalline forms of calcium phosphate appeared and amorphous calcium phosphate progressively changed into carbapatite over the 56-day period. CONCLUSIONS: Infrared spectroscopy yields valuable additional information on the nature and kinetics of the various components of glutaraldehyde-treated tissues after implantation. It may prove to be important in the evaluation of new techniques of calcium mitigation.

Animals↗
PubMed1998

[Re-emergence of tuberculosis and socioeconomic uncertainty].

INTRODUCTION: Infectious diseases are the main cause of morbidity and mortality among socially deprived patients. In 1988-89 the secular decrease in tuberculosis stopped in France as in other industrial countries, and new emergence of the disease has been observed since then, especially among socially deprived patients. CURRENT KNOWLEDGE AND KEY POINTS: Clinical characteristics of tuberculosis remain classical among these patients, but advanced, even historical forms of the disease, are often observed, with frequent extra-pulmonary localizations. Diagnostic and therapeutical procedures must be adapted to the patients' living conditions, including their education and social support. Directly observed therapy is rarely used in France, but the development of adequate strategies for effective primary care management with adapted cost/efficiency ratios in the respect of human rights is essential. FUTURE PROSPECTS AND PROJECTS: Early tracking down of patients lost from follow-up and detailed evaluation of treatment results and social care remain priorities.

Educational Status↗
PubMed1998

CD28 expression in T cell aging and human longevity.

Functional decrements of the immune system have a major contribution to aging and age-related diseases. Here, we further characterize the decline in proportion of CD28-positive T cells previously identified in centenarians. Cohorts of 97 centenarians, 40 subjects aged 70-90 (ELD group), and 40 young adults (under age 40) were phenotyped for T cell surface expression of CD28, CD4, and CD8 antigens. The significant decline in T cells expressing CD28 (p < 10(-4) for comparisons between adults and either ELD or centenarians) affects preferentially the CD8+ subset of T cells. This decline accounts largely for the age-related diminution of T cell responsiveness to mitogenic signals. CD28 expression is modulated in T cell cultures in a growth-related fashion and this modulation is dampened in cultures from centenarians. We propose that the decrease in CD28 expression reflects a compensatory adaptation of the immune system during aging in the face of chronic stimulation.

Adult↗
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↗