Hepatitis and solid organ transplantation.
Explore the source record for details and available documents.
Antiviral Agents↗
Biomedical subjects
J Cadranel
Publications and source records attributed to J Cadranel.
Computed tomographic diagnosis of bronchogenic carcinoma in HIV-infected patients.
PURPOSE: To describe the features of bronchogenic carcinoma (BC) on plain radiography and computed tomography (CT) in human immunodeficiency virus (HIV)-infected patients; to evaluate percutaneous transthoracic needle biopsy (PTNB) in this setting; and to assess outcome. PATIENTS AND METHODS: We reviewed the medical charts, radiographs and chest CT scans in 15 AIDS patients with histologically proven BC. All but one of the patients were young men (mean age 48 years) with a long history of smoking (mean 40 pack-years). Adenocarcinoma was the predominant cell type (46.6%). The stage of the malignancy did not correlate with the CD4 cell count (mean 189 per mm(3)). The diagnosis was obtained by means of PTNB (n=7), bronchoscopy (n=4), thoracotomy (n=2), pleural biopsy (n=1) or extrathoracic biopsy (n=1). RESULTS: Parenchymal masses and nodules were the most common features (66.6%) on chest radiographs and CT. BC was peripheral in 11 cases (73%) and was located in the upper lobe in ten cases (66.6%). Enlarged lymph nodes were present in 60% of patients and metastases in 30%. PTNB was diagnostic in seven of the eight patients who underwent the procedure; complications included two pneumothoraces and one secondary implantation of tumor cells along the needle tract. Three lobectomies and one pneumonectomy were performed for stage I disease. The mean survival time among the patients who underwent surgery was 14 months. These survivals are more encouraging than some of those previously reported in the literature, furthermore, patients die of competing illnesses. CONCLUSION: BC in HIV-infected patients is similar to that in the general population. Early diagnosis can be achieved by means of PTNB. Surgical resection, when feasible, significantly improves survival.
Adult↗
Microscopic polyangiitis with alveolar hemorrhage. A study of 29 cases and review of the literature. Groupe d'Etudes et de Recherche sur les Maladies "Orphelines" Pulmonaires (GERM"O"P).
Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis primarily associated with necrotizing glomerulonephritis and pulmonary capillaritis. In this retrospective study of 29 patients with MPA and alveolar hemorrhage (AH), we characterized the pulmonary manifestations at presentation and assessed the short- and long-term outcome. AH was diagnosed when bronchoalveolar lavage was macroscopically bloody, or contained hemosiderin-laden macrophages, in the absence of lung infection or pulmonary edema. MPA was diagnosed when AH was associated with focal segmental necrotizing glomerulonephritis at kidney biopsy or pathologically proved small-vessel vasculitis. There were 17 women and 12 men, with a mean age of 55.8 +/- 16.7 years. The onset was rapidly progressive, but in 8 (28%) patients, symptoms preceded the diagnosis for more than 1 year. The most constant systemic findings associated with AH were glomerulonephritis in 28 (97%) patients; fever (62%); myalgia and arthralgia (52%); weight loss (45%); ear, nose, and throat symptoms (31%); and skin involvement (17%). Lung opacities were bilateral in 26 (90%) patients, most frequently involving the lower part of the lungs. Bronchoalveolar lavage, performed in 27 patients, was hemorrhagic in 25 (93%), and contained numerous siderophages in others. Most patients were severely anemic (mean hemoglobin, 8.1 +/- 1.8 g/dL). ANCA, present in 27 (93%) patients, gave a perinuclear (14), cytoplasmic (11), or mixed (1) pattern. Mean serum creatinine level was 407 +/- 415 mumol/L. Renal biopsy confirmed the presence of necrotizing glomerulonephritis in 27 patients. Patients were treated with corticosteroids (100%), cyclophosphamide (79%), plasmapheresis (24%), dialysis (28%), and mechanical ventilation (10%). The overall mortality rate was 31% (9 patients). Deaths were related to vasculitis (5 patients) or side effects of treatment (4). Deaths were more frequent in aged or mechanically ventilated patients. The 5-year survival rate was 68%. The recovery of respiratory function among survivors was clinically considered complete in 20 (69%) patients. However, 7 patients (24%) had persistent alterations on pulmonary function tests. Of the 11 patients who had relapses, 2 died from AH.
Adult↗
A persistent challenge: the diagnosis of respiratory disease in the non-AIDS immunocompromised host.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Organizing pneumonia related to common variable immunodeficiency. case report and literature review.
A 68-year-old woman suffering from common variable immunodeficiency (CVI) developed a typical picture of organizing pneumonia. Causative factors other than CVI were eliminated. Several antibiotic regimens failed to improve the patient's condition, while the clinical manifestations rapidly disappeared under steroid therapy, with complete radiological recovery, but relapsed after steroid withdrawal. Finally, organizing pneumonia was definitely demonstrated by pathological findings obtained by open lung biopsy. Interestingly, pathological examination exhibited two other well-known CVI-associated lesions, i.e. benign lymphoid hyperplasia and noncaseating granuloma. In view of reports in the literature, we speculate that these different histological patterns could have resulted in a spectrum of symptomatic CVI-associated pulmonary disorders that improved under steroid therapy.
Aged↗
Virological and molecular characterisation of a new B lymphoid cell line, established from an AIDS patient with primary effusion lymphoma, harbouring both KSHV/HHV8 and EBV viruses.
We report here a new case of primary effusion lymphoma (PEL), occurring in a French homosexual HIV-1 infected male with a pericardial, pleural and mesenteric tumour dissemination, and the establishment from his pleural effusion of a new cell line, Cra-BCBL, dually infected by EBV and KSHV/HHV8. Cra-BCBL cells are of B-cell origin as judged by their clonal immunoglobulin heavy chain (IgH) gene rearrangement, identical to that of the parental tumour. Both the cell line and the lymphoma cells expressed CD38 and CD45 antigens but no classical B-cell or T-cell lineage-restricted antigens. Cra-BCBL harbours a type I EBV virus, expressing a latency type II. Expression of KSHV/HHV8 ORF72 and ORF75 was detected by RT/PCR. In addition, KSHV lytic replication could be induced by treatment by n-butyrate. An equivalent and high copy number of KSHV genomes (20 to 200 copies by cell) was detected both in the primary tumour cells and in the cell line. Southern blot (SB) analysis of EBV terminal repeats (TR) displayed the same unique band in the cell line DNA and in the original tumour cells, consistent with a monoclonal infection of EBV. Furthermore, SB analysis of KSHV/HHV8 TR revealed the same hybridisation pattern between Cra-BCBL and the effusion cells, with a common band at around 30-40 kb corresponding to the fused termini of the viral episomes and a 5 Kb rearranged fragment. The new cell line characterised here could be a useful model to study interactions between two human herpes viruses and their contribution to lymphomagenesis.
Adult↗
[Intrapulmonary solitary or multiple round opacities: diagnostic trends].
Explore the source record for details and available documents.
Adult↗
Reduction of tumour necrosis factor alpha expression and signalling in peripheral blood mononuclear cells from patients with thalassaemia or sickle cell anaemia upon treatment with desferrioxamine.
Recent evidence indicates that the rate of progression of the HIV-1 disease is significantly reduced in thalassaemia major patients upon treatment with high doses of desferrioxamine (DFX). The authors have previously demonstrated that in vitro exposure of mononuclear cells to DFX decreases the bioavailability of tumour necrosis factor alpha (TNF-alpha) which has a stimulatory effect on HIV-1 replication. In this study, therefore, TNF-alpha bioavailability from mononuclear cells isolated from 10 patients with thalassaemia or sickle cell anaemia given DFX as compared to 10 untreated subjects has been evaluated. Evidence is presented showing that DFX treatment reduces TNF-alpha bioavailability (P<0.05) by inhibiting its steady state (P<0.05) and by enhancing its inactivation through binding to soluble TNF-alpha receptor type II (P<0.05). We also show that DFX treatment limits the in vivo activation of NF-kappaB, a transcription factor involved in both TNF-alpha gene transcription and TNF-alpha signalling (P<0.005). We conclude that TNF-alpha bioavailability and signalling are impaired in patients upon DFX treatment. This mechanism may contribute to delayed progression of the HIV-1 infection in vivo.
Adolescent↗
Lymphoma of pulmonary mucosa-associated lymphoid tissue: CT scan findings and pathological correlations.
The aim of this study was to describe the lesions of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma observed by means of computed tomography (CT) and to determine the value of CT in the management of this disease. Sixty six CT scans were performed in 13 consecutive cases of histologically proven pulmonary MALT lymphoma at the time of diagnosis (n=13) or periodically (n=53). They were reviewed separately with chest radiographs by consensus between two observers. Pulmonary abnormalities were described and compared to histopathological findings on surgical specimens from seven patients. At the time of diagnosis, elementary lesions observed by means of CT consisted of nodular areas of attenuation (12 of 13), linear areas of attenuation (eight of 13) and consolidations (six of 13). All these lesions were centred on airways that appeared dilated in seven cases and were more often bilateral and multiple on CT than on the chest radiographs. CT abnormalities correlated with gross pathological appearance and were related to a lymphomatous infiltration with a peribronchovascular distribution. Pathological examination also confirmed the presence of dilated airways within lymphomatous lesions and showed that the bronchial wall was respected. During follow-up, in patients on chemotherapy, response, relapse or progression were easily identified by means of plain radiography. In the initial evaluation, computed tomography contributed to the choice of therapeutic strategy, avoiding unnecessary surgical resection in one-third of patients. By contrast, it is unclear whether computed tomography is useful for post-treatment follow-up of mucosa-associated lymphoid tissue.
Adult↗
Tuberculosis in AIDS: past or new problems?
Explore the source record for details and available documents.
AIDS-Related Opportunistic Infections↗
Pulmonary malignancies in the immunocompromised patient.
Clinicians should be familiar with immunodeficiency-related malignancies, as their incidence is expected to increase further with the rise in the number and survival of immunocompromised patients. The most common malignancies affecting the lungs in those patients are Kaposi's sarcoma, non-Hodgkin's lymphoma and, to a far less extent, Hodgkin's disease and bronchogenic carcinoma. However, their relative frequency depends on the types of immune deficiency, including those due to congenital disorders, AIDS and drug treatments. This review will summarize epidemiological data on the frequency of immmunodeficiency-related malignancies, recent advances on their pathogenesis and current approaches to their diagnosis and treatment in the various immunosuppressed groups.
Acquired Immunodeficiency Syndrome↗
Sarcoid-like pulmonary disorder in human immunodeficiency virus-infected patients receiving antiretroviral therapy.
We report two cases of HIV-infected patients who presented with diffuse interstitial micronodular lesions on chest X-ray after institution of protease inhibitor-containing highly active antiretroviral therapy (HAART). Granulomatous pulmonary disorder mimicking sarcoidosis was diagnosed on histopathological studies revealing noncaseating granuloma and bronchoalveolar lavage analysis showing an intense CD4(+) lymphocyte alveolitis. Causative agents such as infectious organisms and environmental compounds were excluded. The relationship between sarcoid-like reaction and immune reconstitution under HAART is discussed.
Anti-HIV Agents↗
AIDS-related Pneumocystis carinii pneumonia in the era of adjunctive steroids: implication of BAL neutrophilia.
Factors predictive of mortality in patients with AIDS and Pneumocystis carinii pneumonia (PCP) were identified before the introduction of adjunctive steroids, but they have not been reevaluated since. Because PCP still occurs in AIDS, remaining fatal in some cases, we conducted a multivariate analysis of factors predicting mortality in patients with HIV-positive PCP managed from 1990 to 1995, i.e., after the consensus conference on the use of adjunctive steroids. The predictive value of clinical, laboratory, and bronchoalveolar lavage (BAL) data at admission and during the course of PCP was studied retrospectively using multivariate methods, in 144 patients with AIDS. Overall mortality was 21.5%. The univariate analysis identified seven factors predictive of 90-d mortality: Pa(O(2)) on room air < 60 mm Hg, lactate dehydrogenase > 1,000 IU, albuminemia < 30 g/L, BAL neutrophilia > 10%, nosocomial infection, pneumothorax, and a need for mechanical ventilation. Four of these factors were independently associated with 90-d mortality in the multivariate analysis; among them, two were evaluable at admission, namely, Pa(O(2)) < 60 mm Hg on room air and BAL neutrophilia > 10%, and two during hospitalization, namely, the development of pneumothorax and a need for mechanical ventilation. Moreover, BAL neutrophilia was correlated to occurrence of pneumothorax and a need for mechanical ventilation. In the era of adjunctive steroid use, AIDS-related PCP remains fairly common. Two independent factors evaluable at admission, Pa(O(2)) on room air and BAL neutrophilia, are predictive of death.
AIDS-Related Opportunistic Infections↗
Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms.
Transforming growth factor (TGF)-beta1 is a growth factor involved in the mechanisms of lung repair and fibrosis that follow inflammatory processes. We sought to examine the link between the generation of reactive oxygen intermediates (ROI) or reactive nitrogen intermediates (RNI) by inflammatory cells and the expression of TGF-beta1 by alveolar epithelial cells. Exposure of the A549 lung epithelial cell line to either an ROI generating system (xanthine and xanthine oxidase) or an RNI donor (S-nitroso-N-acetyl-penicillamine [SNAP]) promoted a time- and dose-dependent increase in TGF-beta1 release, as measured by a specific enzyme-linked immunosorbent assay. At the peak, the levels of TGF-beta1 were twice the control values. The induction of TGF-beta1 release by ROI was blunted by catalase and unaffected by superoxide dismutase, indicating the involvement of hydrogen peroxide. The response was also blunted by 5, 6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), a specific RNA polymerase II inhibitor, and accompanied by a corresponding increase in TGF-beta1 messenger RNA, as measured by quantitative/competitive reverse transcription polymerase chain reaction, suggesting the involvement of transcriptional mechanisms and possibly other downstream mechanisms. In contrast, RNI-induced TGF-beta1 release was unaffected by DRB and blunted by the protein synthesis inhibitor cycloheximide, suggesting the involvement of translational and post-translational mechanisms. This response required cyclic guanosine monophosphate (cGMP)- mediated processes because (1) immunoreactive cGMP accumulated in the culture medium of SNAP-treated cells; (2) SNAP-induced TGF-beta1 release was blunted by KT 5823, an inhibitor of cGMP-dependent protein kinase; and (3) similar increase in TGF-beta1 release was obtained by cell exposure to membrane-permeable dibutyryl-cGMP or to atrial natriuretic factor, a known agonist of particulate guanylate cyclase. These data suggest that in vitro exposure of human alveolar epithelial cells to ROI and RNI enhances TGF-beta1 release through different mechanisms. In vivo, this control may constitute a molecular link between inflammatory and fibrotic processes.
Arginine↗
Primary pulmonary AIDS-related lymphoma: radiographic and CT findings.
STUDY OBJECTIVES: To describe the radiographic and CT findings of primary AIDS-related lymphoma (ARL) of the lung (ARLL), and to evaluate percutaneous transthoracic needle biopsy (PTNB) in the diagnosis of primary ARLL. MATERIALS AND METHODS: Seven chest radiographs and seven CT scans of HIV-infected patients with histologically proved primary pulmonary non-Hodgkin's lymphoma (PPL) were reviewed at our institution. All of the patients had fibroscopy with BAL. The diagnosis of PPL was established histologically by means of PTNB (n = 4), open-lung biopsy (n = 2), or autopsy (n = 1). RESULTS: All but one patient had multiple peripheral well-defined nodules of various sizes on the chest X-ray film and CT scan. One patient had a subpleural parenchymal infiltrate and another had a main peripheral mass with spontaneous cavitation. Hilar/mediastinal adenopathies and pericardial/pleural effusion were never associated with the parenchymal abnormalities. Fibroscopy with BAL was always negative. PTNB, done in six cases, was diagnostic in four cases and suggested primary ARLL in two cases. No complications occurred during these procedures. CONCLUSION: After excluding infectious causes, multiple peripheral nodules and/or masses without hilar or mediastinal adenopathies and without pleural effusion are suggestive of primary pulmonary ARL. A specific diagnosis can be obtained by means of PTNB.
AIDS-Related Opportunistic Infections↗
[Diffuse interstitial pneumopathy. Etiology and diagnosis].
Explore the source record for details and available documents.
Acute Disease↗
AIDS-related primary pulmonary lymphoma.
We describe 12 cases of AIDS-related primary pulmonary lymphoma occurring between 1986 and 1996 in a large French cohort of HIV-infected patients. Diagnostic criteria were: (1) histologically proven lymphomatous pulmonary involvement; (2) absence of mediastinal and/or hilar adenopathy on chest radiography; (3) absence of extrathoracic lymphoma extension. All patients were severely immunodeficient at the time of diagnosis. All but one patient presented with B and/or nonspecific respiratory symptoms. Chest radiography showed one or more marginated nodule(s) or large mass. CT scan showed a cavitary lesion in five patients. No lymph node enlargement or specific pleural effusion was detected. Transthoracic needle biopsies were performed in 10 patients and avoided open-lung biopsy for the diagnosis of lymphoma in five patients. All but one of the primary pulmonary lymphoma were high-grade B-cell non-Hodgkin's lymphomas. Using antilatent membrane protein-1 antibodies and an Epstein-Barr-Virus-encoded RNA transcript-specific probe, latent EBV infection of tumor cells was demonstrated in every case. All but one of the patients received chemotherapy. The median survival time was 4 mo, and no patient was still alive at the cut-off date for this analysis. Progessive pulmonary lymphoma was the main cause of death, but infections were also frequent.
AIDS-Related Opportunistic Infections↗
Neutrophil alveolitis in bronchioloalveolar carcinoma: induction by tumor-derived interleukin-8 and relation to clinical outcome.
Tumor infiltrate, predominantly constituted by lymphocytes, may represent an important prognostic factor in bronchioloalveolar carcinoma (BAC), in addition to tumor extension and histological type. In the present study, we determined the presence, the origin, and the prognostic importance of neutrophils that also participate in leukocyte infiltrates of BAC. Neutrophil alveolitis was determined immunohistochemically in both lung biopsies and bronchoalveolar lavage (BAL) fluid samples from 29 patients with histologically proved BAC. The local expression of interleukin (IL)-8 was determined by immunohistochemical and immunoenzymatic techniques. Neutrophil counts were analyzed in relation to the clinical outcome of patients by the Kaplan-Meier method and Cox's univariate and stepwise multivariate models. Lymphocytes and neutrophils dominated the inflammatory cell population in the lower respiratory tract of patients with BAC. Neutrophils were located mainly in the alveolar lumen and seldom in alveolar wall whereas lymphocytes were exclusively present in alveolar wall. A relationship was observed between the number of neutrophils and the level of IL-8 in BAL fluid suggesting the involvement of that chemokine in neutrophil recruitment. The tumor cells were the predominant cells that appeared to express IL-8 by immunolocalization. The presence of increased numbers of neutrophils was significantly associated with a poorer outcome in patients with BAC (P = 0.02). In a multivariate analysis, the neutrophil percentage in BAL fluid was an independent predictor of clinical outcome. The risk of death was increased substantially (rate ratio, 5.2; 95% confidence interval, 1.1 to 24.7) among patients with BAL neutrophil percentage of > or = 39% (median of the distribution) as compared with the others. In BAC, neutrophils accumulate in the alveolar lumen. Elaboration of IL-8 by tumor cells may be responsible for this event, which is associated with a significantly higher risk of death.
Adenocarcinoma, Bronchiolo-Alveolar↗