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Biomedical subjects

J Cadranel

Publications and source records attributed to J Cadranel.

At least 73 records · Page 4Linked to original sources

[HIV replication and pulmonary opportunistic infections].

The lung is a privileged target of opportunistic pathogens during HIV infection, due to the dramatic immunodeficiency which characterizes the disease. Proviral forms of the virus are frequently detected in the lung, particularly in macrophages, which constitute an important viral reservoir, and in T lymphocytes. The frequency of these proviral forms increases in the lung with the progression of the HIV disease. Some opportunistic pathogens themselves, or the mediators produced during immune responses toward these pathogens, are able to activate in vitro the HIV replication. An important increase of viral load is observed in the lung during P. carinii pneumonia and during tuberculosis. It has been shown that tuberculosis generated a microenvironment able to activate T lymphocytes present at the site of the disease and to increase their productive infection by HIV. TNF alpha and IL6, among other cytokines, could be involved in this phenomenon. The massive replication of HIV during pulmonary infections could influence the general prognosis of the disease through the increase of the systemic viral load. In this context, new therapeutic strategies might have to be defined, including not only a wider prophylaxis but also antiretroviral treatments at the time of infectious episodes.

AIDS-Related Opportunistic Infections↗

[Intramedullary metastases of bronchogenic carcinoma. Two cases].

Intramedullary metastases are uncommon. We report two cases in patients with small cell bronchogenic cancer. The clinical diagnosis was supported by T1 magnetic resonance imaging after gadolinium injection. A unique medullary metastasis associated with other metastatic localizations was observed in the first patient and multiple intramedullary metastases alone in the second. These secondary intramedullary localizations were highly sensitive to chemotherapy after the first monthly cure in the first patient and after the third in the second patient. We emphasize the importance of chemotherapy in such cases, usually associated with focal radiotherapy.

Aged↗

[Acute respiratory insufficiency in patients with bronchopulmonary cancer].

Acute respiratory failure is relatively frequent in patients with bronchogenic cancer. The respiratory disorder may be related to tumor extension itself or opportunistic infection above or below the tumoral stenosis. Radiotherapy and chemotherapy can also be causal. The condition is particularly serious in patients with one lung. We discuss the different complications, their frequency and conditions of occurrence.

Acute Disease↗

[Pulmonary crytosporidium in a patient with AIDS].

Compared to digestive disorders, respiratory disease linked to cryptosporidium has not been very well documented in AIDS. We report a case of a patient suffering from AIDS who presented with chronic bronchial symptoms which became more and more incapacitating. Different respiratory specimens (broncho-alveolar lavage, expectoration and bronchial biopsy) revealed the presence of cryptosporidium species. The patient died in a few weeks from respiratory insufficiency without the parasite being eradicated from the bronchi. Although the autopsy confirmed the presence of cryptosporidium species, it was difficult to confirm its responsibility due to the fact that other pathogens were present in the bronchial tree.

AIDS-Related Opportunistic Infections↗

Tuberculosis generates a microenvironment enhancing the productive infection of local lymphocytes by HIV.

Tuberculosis (TB) contributes to the progression of HIV disease but, so far, the mechanism involved is not clear. Several cytokines accumulating in vivo at the site of mycobacterial infection up-regulate HIV expression in vitro. In this study, we assessed the role of pleural fluids recovered from seronegative patients with TB on HIV replication in acutely infected blast cells. Pleural fluids from subjects with congestive heart failure served as controls. In all cases, TB pleural fluids stimulated HIV replication in vitro. TNF-alpha, IL-6, IFN-gamma, and granulocyte/macrophage (GM)-CSF, as well as very low levels of IL-2, were detected in TB pleural fluids. An anti-IL-2 Ab preincubated with TB pleural fluids exhibited no blocking effect on HIV replication similarly to anti-IFN-gamma and anti-GM-CSF Abs. In contrast, anti-TNF-alpha and anti-IL-6 Abs decreased HIV replication by 60 and 90%, respectively. Recombinant TNF-alpha and IL-6 stimulated HIV replication, while IFN-gamma and GM-CSF had a more ambiguous role. The capacity of pleural fluids to stimulate HIV replication was specific for TB, since the capacity of control fluids was significantly lower. Finally, in contrast to PBL, which require in vitro activation for their productive infection by HIV, unstimulated tuberculous pleural lymphocytes were productively infectable by HIV. Taken together, our data suggest that the microenvironment generated by TB might increase the HIV burden in infected subjects, partly through cytokines other than IL-2, namely TNF-alpha and IL-6.

Bronchoalveolar Lavage Fluid↗

Fulminant Pneumocystis carinii pneumonia in 4 patients with dermatomyositis.

Between 1989 and 1996, 4 cases of Pneumocystis carinii pneumonia (PCP) were observed in patients seronegative for the human immunodeficiency virus who were receiving corticosteroid therapy for dermatomyositis in our institution. These cases were considered unusual in light of the short delay of their onset after initiation of immunosuppressive therapy and their fulminant course: 3 of these patients died of PCP occurring during the first month of treatment with prednisone. In all 4 patients lymphopenia was observed before the initiation of corticosteroid treatment and low CD4 and CD8 cell counts were evident at the time of PCP. These observations support the view of an increase in both the severity and incidence of PCP in patients without human immunodeficiency virus infection and question the need for a primary prophylaxis in patients with connective tissue diseases receiving high-dose corticosteroid therapy.

Adult↗

Diagnosis of smear-negative pulmonary tuberculosis using sequence capture polymerase chain reaction.

Techniques based on the polymerase chain reaction (PCR) can be used to rapidly identify DNA from Mycobacterium tuberculosis in clinical samples from patients with tuberculosis, but prior studies evaluating this approach in the diagnosis of paucibacillary forms of pulmonary tuberculosis have reported poor sensitivity and/or specificity. We have developed a procedure in which mycobacterial DNA in crude samples is specifically captured prior to amplification, thereby concentrating the target sequences and removing irrelevant DNA and other inhibitors of the amplification reaction (sequence capture PCR). To evaluate the usefulness of this approach in the diagnosis of paucibacillary forms of pulmonary tuberculosis, sequence capture PCR was performed prospectively on samples of bronchoalveolar lavage fluid from consecutive patients suspected of having pulmonary tuberculosis but for whom three consecutive samples of respiratory secretions were smear negative. Of the 27 patients evaluated, active tuberculosis was diagnosed in nine; sequence capture PCR was positive for all of these patients, including the three for whom all specimens submitted for culture were negative. No positive results were obtained for lavage fluid from the 18 patients for whom the diagnosis of active tuberculosis was subsequently excluded or 25 additional patients undergoing bronchoalveolar lavage for evaluation of other pulmonary problems, even though many of these patients had a history of prior tuberculosis or radiographic evidence of prior tuberculous infection. Paucibacillary forms of pulmonary tuberculosis can be rapidly identified with high sensitivity and specificity using sequence capture PCR performed on samples obtained by bronchoalveolar lavage.

Adult↗

Insulin-like growth factors and their binding proteins in pleural fluid.

We investigated the expression and potential regulatory role of insulin-like growth factors (IGFs) and their specific binding proteins (BPs) in tuberculous and nontuberculous pleuritis. By using a radioimmunoassay after acid gel filtration chromatography, we found that mean concentrations of IGF-I were 211.9 +/- 20.2 microg/l and 203.2 +/- 31.1 microg/l in pleural fluid of 14 patients with tuberculous pleuritis and 9 patients with malignant pleuritis respectively. These values were near those in serum of the same patients (221.3 +/- 19.5 microg/l and 204.6 +/- 21.0 microg/l respectively). By using a specific protein-binding assay, we found that mean concentrations of IGF-II were 345.3 +/- 61.0 microg/l and 167.6 +/- 22.7 microg/l in tuberculous and malignant pleural effusions respectively. These values were significantly lower than those in serum of the same patients (628.3 +/- 79.0 microg/l, P<0.025 and 532.0 +/- 85.9 microg/l, P<0.025 respectively). Because bioavailability and bioactivity of IGFs may be regulated by their binding to IGFBPs, we studied IGFBP patterns in the pleural fluid of 6 patients with tuberculous pleuritis. As assessed by Western ligand blotting the levels of IGFBP-1 and IGFBP-2 were increased whereas those of IGFBP-3 were decreased in pleural fluid in comparison with serum. The decrease in IGFPB-3 levels reflected increased proteolysis, as assessed by Western immunoblotting. In spite of this presence of IGFBPs, IGFs could be responsible for the local biosynthesis of 1.25-dihydroxyvitamin D (1,25-(OH)2D) since pleural fluid levels of both IGF-I and IGF-II significantly correlated with those of 1,25-(OH)2D. These results indicate that IGFs are detectable in pleural fluid and may contribute to control the activity of 25-hydroxyvitamin D-1alpha hydroxylase in tuberculous pleuritis.

Adult↗

[Primary pulmonary lymphoma].

There are three distinct clinico-anatomical entities today covered by the definition of a primary clonal pulmonary lymphoid proliferation. These are pulmonary lymphomas of B cell phenotype, of low grade malignancy, B cell lymphomas of high grade malignancy and finally lymphomatoid granulomatosis whose clonal characteristic is sometimes difficult to confirm. This general review aims to specify the pathophysiological, diagnostic, prognostic and therapeutic aspects of these different types. Low grade B cell lymphoma is the most common pulmonary lymphoma. Their development depends on mucosa associated lymphoid tissue. They are most often indolent and present as a chronic alveolar opacity. Their prognosis is excellent and the modalities of treatment are discussed (no therapy, surgery or monochemotherapy). High grade B cell pulmonary lymphomas are much rarer and may result from the transformation of a low grade lymphoma or arise in a particular situation such as imunodepression. Their prognosis is poor and the therapeutic possibilities depend most often on the underlying disease. The presence of lymphomatoid granulomatosis in this group of pulmonary lymphomas is debatable. The demonstration of a clonal character of this proliferation is practically never obtained and there is often extra pulmonary disease. The prognosis of this type of illness is extremely variable because certain studies have shown a cure using corticosteroids and cyclophosphamide whilst others have found that the disease is always fatal in spite of using strong polychemotherapy.

Humans↗

[Multicentric Castleman's disease with mediastinal involvement in a patient with HIV infection].

Castleman's disease is most often seen by a thoracic physician as a mediastinal tumour which is discovered fortuitously and whose surgical excision leads to a cure. We report a case of a patient of 30 who was seropositive for HIV and was suffering from Castleman's disease initially localised to the mediastinum. The disease was associated with a cutaneous and bronchial Kaposi sarcoma. The mediastinal disease, associated with cutaneous and bronchial Kaposi sarcoma, was marked by evolving in a multicentric manner. We review the histological definition and recent data concerning the pathophysiology and the diagnostic and therapeutic management of this disorder and the very varied clinical expression.

Adult↗

[Pulmonary mucormycosis in a leukemia patient. Diagnostic and therapeutic difficulties].

The observation of pulmonary mucormycosis occurring in a patient presenting with aplasia induced therapeutically during treatment for acute myeloblastic leukaemia, has led to a review of the characteristics of this rare opportunistic fungal infection: it occurs in a particular condition; the clinical manifestations are characterised by the thrombotic character and the rapidly necrosing nature of the histological lesions; the diagnosis is usually very difficult to make and is linked to the rarity of the pathology and the frequently negative mycological specimens apart from tissue biopsies; the value of a medicosurgical therapeutic strategy on which the prognosis of the infection depends.

Amphotericin B↗

[From pseudolymphomas to primary pulmonary lymphomas of MALT type].

Primary lung lymphomas are uncommon and the use of immunohistochemical and molecular biological techniques have widely contributed to their understanding. Generally, they are of low grade malignancy and most develop from mucosa-associated lumphoid tissue (MALT). Cellular analyses of samples obtained routinely by endoscopy (transbronchial biopsy or bronchoalveolar lavage) will probably enable the clinician to avoid invasive diagnostic procedures, such as surgical lung biopsy. Treatment of limited forms is usually surgical. As to bilateral forms or those with lesions of other mucosae e.g. gut, the best therapeutic strategy remains to be defined.

Diagnosis, Differential↗

Cytomegalovirus-induced alveolar hemorrhage in patients with AIDS: a new clinical entity?

We report five cases of alveolar hemorrhage associated with intravascular hemolysis in patients with AIDS. Cytomegalovirus was the only pathogen recovered from the lungs of these patients. There was evidence of multivisceral spread of the virus in all patients, and all had viremia. All had clinical, biological, and pathological features of pulmonary vasculitis, and the conditions of four improved with specific anti-cytomegalovirus therapy.

AIDS-Related Opportunistic Infections↗

Sequence capture-PCR improves detection of mycobacterial DNA in clinical specimens.

The rapid identification of mycobacterial DNA in clinical samples by PCR can be useful in the diagnosis of tuberculous infections, but several large studies have found that the sensitivity of this approach is not better than that of culture. In order to improve the sensitivity of detection of mycobacterial DNA in clinical specimens from patients with paucibacillary forms of tuberculosis, we have developed a procedure permitting the specific capture of mycobacterial DNA in crude samples prior to amplification, thereby concentrating the target sequences and removing irrelevant DNA and other potential inhibitors of the amplification reaction (sequence capture-PCR). By using this approach to capture and amplify two different sequences specific for organisms of the Mycobacterium tuberculosis complex (IS6110 and the direct repeat region), it was possible to detect as little as one genome of mycobacterial DNA in samples containing up to 750 micrograms of total DNA, representing a 10- to 100-fold increase in sensitivity compared with that obtained by purifying total DNA prior to amplification. Detection of the IS6110 sequence in pleural fluid samples from patients with tuberculous pleurisy by sequence capture-PCR gave positive results in 13 of 17 cases, including 3 of 3 culture-positive samples and 10 of 14 culture-negative samples. In contrast, when total DNA was purified from these samples by adsorption to a silica matrix prior to amplification, only the three culture-positive samples were positive by PCR. The sensitivity of detection of the direct repeat sequence in these samples by sequence capture-PCR was similar to that of IS6110 and, in addition, permitted immediate typing of the strains from some patients. We conclude that sequence capture-PCR improves the sensitivity of detection of mycobacterial DNA in paucibacillary samples. This approach should be useful in detecting rare target sequences from organisms implicated in other pathologic processes.

Adult↗