[Valganciclovir maintenance therapy in AIDS: treatment failure due to the development of cytomegalovirus resistance to ganciclovir].
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Biomedical subjects
Publications and source records attributed to M Merad.
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The diagnostic of invasive fungal infection is often difficult because of the low sensitivity of fungal culture from infected tissues. Here we have assessed the ability of a panfungal PCR targeted on the DNA region encoding the RNA genes followed by sequencing of the amplification products to detect and identify fungi from tissue biopsies. This assay allowed us to identify the microorganism responsible for an invasive fungal infection in three of our patients. In two cases, hepatosplenic candidiasis was suspected and Candida albicans DNA was detected from liver biopsies. The third patient was cared for a thymome and developed a manubrium osteitis caused by Scedosporium apiospermum.
The prognosis of HIV infection has been modified by antiretroviral therapy. However, the morbidity and the mortality of HCV co-infection increase and may be a major problem of health service. Up to now co-infected patients are excluded of transplantation due to complexity, the ethical aspects, the immunodeficiency and the co-infection. This study tries to estimate the feasibility in this population. Between December 1999 and March 2002, seven patients were transplanted. The average of CD4 was 332/ml; the viral load was <50 copies/ml. Before transplantation, no patient had experienced opportunist infection and all patients received antiretroviral therapy adapted to their history. The average follow-up is of 14 months: one patient died 3 months after transplantation, the other one presented a candida in oesophagus, the average of CD4 was 280/ml, and viral load was <50 copies/ml in five patients. A relapse of HVC was observed in all patients. Interferon/rivabirine therapy was proposed for four patients. Every patient received tacrolimus and corticoids. HAART were modified four times for toxicity and one time for virological failure. We observed two cases of transient renal insufficiency, two cases of diabetes, two cases of pancreatitis, and abnormalities of the respiratory mitochondrial chain in four patients. Finally, liver transplantation in HIV-HCV co-infected patients seems to be feasible when strict criteria of selection are taken into account. This still experimental strategy requires a multidisciplinary partnership.
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Giant cell tumour (GCT) is usually considered a benign entity. A small fraction of these tumours become malignant with time, and an extremely rare fraction may be malignant at onset. We report herein an unusual case of primary malignant GCT of the bone that relapsed locally with the same histology 14 years after a simple surgical curettage.
Dendritic cells (DCs) are professional antigen-presenting cells which both initiate adaptive immune responses and control tolerance to self-antigens. It has been suggested that these different effects on responder cells depend on subsets of DCs arising from either myeloid or lymphoid hematopoietic origins. In this model, CD8 alpha+ Mac-1- DCs are supposed to be of lymphoid while CD8 alpha- Mac-1+ DCs are supposed to be of myeloid origin. Here we summarize our findings that both CD8 alpha+ and CD8 alpha- DCs can arise from clonogenic common myeloid progenitors (CMPs) in both thymus and spleen. Therefore CD8 alpha expression DCs does not indicate a lymphoid origin and differences among CD8 alpha+ and CD8 alpha- DCs might rather reflect maturation status than ontogeny. On the basis of transplantation studies, it seems likely that most of the DCs in secondary lymphoid organs and a substantial fraction of thymic DCs are myeloid-derived.
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Dendritic cells (DCs) are critical in both initiating adaptive immune responses and maintaining tolerance to self antigens. These apparently contradictory roles have been suggested to depend on different subsets of DCs that arise from either myeloid or lymphoid hematopoietic origins, respectively. Although DC expression of CD8alpha is attributed to a lymphoid origin, here we show that both CD8alpha+ and CD8alpha- DCs can arise from clonogenic common myeloid progenitors in both thymus and spleen. Thus, expression of CD8alpha is not indicative of a lymphoid origin, and phenotypic and functional differences among DC subsets are likely to reflect maturation status rather than ontogeny.
Bone marrow-derived dendritic cells (DC) represent a family of antigen-presenting cells (APC) with varying phenotypes. For example, in mice, CD8alpha(+) and CD8alpha(-) DC are thought to represent cells of lymphoid and myeloid origin, respectively. Langerhans cells (LC) of the epidermis are typical myeloid DC; they do not express CD8alpha, but they do express high levels of myeloid antigens such as CD11b and FcgammaR. By contrast, thymic DC, which derive from a lymphoid-related progenitor, express CD8alpha but only low levels of myeloid antigens. CD8alpha(+) DC are also found in the spleen and lymph nodes (LN), but the origin of these cells has not been determined. By activating and labeling CD8alpha(-) epidermal LC in vivo, it was found that these cells expressed CD8alpha on migration to the draining LN. Similarly, CD8alpha(-) LC generated in vitro from a CD8 wild-type mouse and injected into the skin of a CD8alphaKO mouse expressed CD8alpha when they reached the draining LN. The results also show that CD8alpha(+) LC are potent APC. After migration from skin, they localized in the T-cell areas of LN, secreted high levels of interleukin-12, interferon-gamma, and chemokine-attracting T cells, and they induced antigen-specific T-cell activation. These results demonstrate that myeloid DC in the periphery can express CD8alpha when they migrate to the draining LN. CD8alpha expression on these DC appears to reflect a state of activation, mobilization, or both, rather than lineage. (Blood. 2000;96:1865-1872)
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Both nature and prognosis of cardiac complications occurring in patients infected by the Human Immunodeficiency Virus-1 (HIV-1) have changed considerably since the introduction of highly acive and anti-retroviral triple therapy ("HART"). Opportunist cardiac infections have thus been displaced and side effects of drugs now occupy the primary aetiological role. Torsades de pointe may be exceptionally triggered by anti-infectious agents such as pentacarinat or trimethoprime-sulfamethoxazole, as are those induced by the association of ketoconazole and terfenadine or cisapride, the dangers of which are well known and the prevention more effective, especially with the association with HIV antiproteases which inhibit the cytochrome P450. The diagnosis of iatrogenic myocardial dysfunction is more difficult, except when it occurs acutely as with phosphonoformate (Foscarnet), or interleukine-2. Progressive cardiomyopathy caused by -interferon and dideoxynucleosides (zidovudine, didanosine and zalcitabine), reversible on withdrawal of the drug responsible in half the cases, should be distinguished from those due to the HIV itself (therapeutic relay) or to another associated cause (alcohol, coronary artery disease). The coronary complications of diseases treated by antiproteases usually occur in smokers whose cholesterol and triglyceride levels are rapidly increased with HAART. In a series of 9 patients (amongst 700 treated with the antiproteases), after the acute phase of myocardial infarction during which the interventional approach is often preferred, the medium-term prognosis is relatively good, on condition that the patients correct the hyperlipidaemia and give up smoking.
An anomalous origin of the left coronary artery arising from the pulmonary artery is a congenital malformation rarely described in adults. We report the case of a 65-year-old patient with this anomaly. Clinical presentation, imaging identification (coronary angiogram, MRI and electron-beam CT), surgical treatment and angiographic long-term follow-up are described.
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We report the case of a female patient who developed a second contralateral small cell lung carcinoma (SCLC) five years after a right upper lobe SCLC treated by sequential chemotherapy and chest radiation therapy. This second primary neoplasia was revealed by an isolated and symptomatic syndrome of inappropriate antidiuretic hormone secretion. Specific evolution of long-term survivors after SCLC are discussed, including consequences of combined radiochemotherapy and poor prognosis associated with persistence of tobacco smoking exposure.
The combination of interferon-alpha (IFN-alpha) plus interleukin (IL-2) has been accepted in the treatment of metastatic renal cell carcinoma (MRCC), whereas vaccines based on IL-12 or dendritic cells (DCs) are still being investigated. Here the authors analyzed 1) the feasibility to generate functional monocyte-derived DCs (MDDCs) from patients treated with biological response modifiers (BRMs) who have MRCC, 2) the phenotypic modulations of these MDDCs during BRM treatment. Eight and 13 MRCC patients received IL-2 plus IFN-alpha or IL-12 immunotherapy, respectively. The adherent fraction of mononuclear cells from patients' blood drawn before, during, and after immunotherapy was incubated in clinically approved culture medium supplemented with 5% autologous serum, rhu granulocyte macrophage colony-stimulating factor, and rhuIL-4 for a week. At day 7 or 8 of culture, floating cells were examined in flow cytometric and functional assays (alloreactivity, proliferation assays in the presence of tetanus toxoid or tumor peptides, IL-12 secretion). In all patients except two, MDDCs could be generated but at a lower rate compared with healthy volunteers. Morphologic and phenotypical analyses revealed immature DCs with low levels of CD1a or CD83 expression throughout therapy with BRMs. Capacities in mixed leukocyte reactions were similar to those of healthy volunteers and stable during immunotherapy, whereas presentation of major histocompatibility complex class II tetanus toxoid peptide complexes was slightly enhanced during and after IL-12 therapy. IL-12 expression levels under IFN-gamma and CD40L stimulation were significantly lower in MDDC cultures from patients with MRCC compared with healthy volunteers. Overall, peripheral blood mononuclear cells from a cohort of 21 patients with metastatic disease who were treated with BRMs maintained their ability to differentiate into functional MDDCs with no selective quantitative or qualitative advantage.
With the advent of helical CT, the capability of noninvasive imaging of the thoracic aorta has been enhanced considerably. In this article, we describe the potential of helical CT using dual-slice technology to evaluate thoracic aortic diseases such dissection, aneurysm, trauma, infection, inflammation, thromboembolic disease, and postoperative complications. Technical considerations for optimal CT imaging as well as limitations of helical CT are highlighted.
Radiation therapy is used to treat many intrathoracic and chest wall malignancies. A variety of changes may occur after radiation therapy to the thorax. Radiation therapy produces dramatic effects in the lung. Pulmonary necrosis is an uncommon, severe, late complication of adjuvant postoperative radiation therapy. Bronchiolitis obliterans with organizing pneumonia is a distinct clinicopathologic entity characterized by patchy, migratory, peripheral air-space infiltrates. Radiation therapy can also cause spontaneous pneumothorax, mesothelioma, and lung cancer. In the mediastinum, radiation therapy may cause thymic cysts, calcified lymph nodes, and esophageal injuries. Cardiovascular complications of radiation therapy are often delayed and insidious. Premature coronary artery stenosis occurs after radiation therapy to the mediastinum. Radiation therapy may also give rise to calcifications of the ascending aorta, pericardial disease, valvular injuries, and conduction abnormalities. Women who undergo thoracic irradiation before the age of 30 years have a high risk of developing a second breast cancer. Radiation-induced sarcomas are an infrequent but well-recognized complication of radiation therapy. Other chest wall injuries due to radiation therapy are osteochondroma and rib or clavicle fractures. Knowledge of the imaging features of injuries caused by radiation therapy can prevent misinterpretation as recurrent tumor and may facilitate further treatment.