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J Cadranel

Publications and source records attributed to J Cadranel.

At least 37 records · Page 2Linked to original sources
PubMed2003

Splice mutations in the p53 gene: case report and review of the literature.

Splice mutations in the p53 gene (TP53) are described as rare events that occur at a frequency of less than 1%. Using a functional assay based on the transcriptional activity of p53 and using RNA as starting material, we describe here a p53 splice mutation that could not be detected by genomic sequencing. This lack of detection is due to a deletion of the region complementary to primers commonly used for amplification. Reviewing the literature, we show that p53 splice mutations have been certainly underestimated and that careful strategy should be used for a complete mutational analysis of the p53 gene. Furthermore, some p53 gene mutations described as "neutral" due to the absence of any amino-acid change are truly deleterious, as they affect gene splicing.

Alternative Splicing↗
PubMed2003

Interstitial lung disease in amyopathic dermatomyositis, dermatomyositis and polymyositis.

This study investigated interstitial pneumonia associated with amyopathic dermatomyositis, dermatomyositis and polymyositis, paying particular attention to muscular and/or cutaneous manifestations and their chronology relative to lung involvement. Patients included four males and 13 females, aged 51.7+/-10.8 yrs, who had surgical lung biopsy. Diagnoses included dermatomyositis (10 patients), polymyositis (four patients) and amyopathic dermatomyositis (three patients). Solitary respiratory manifestations preceded the onset of any skin or muscle disease in four cases (24%). Reticular and ground glass opacities were the most frequent computed tomography (CT) findings. Pathological review showed nonspecific interstitial pneumonia (eleven, 65%; cellular, two; cellular and fibrotic, five; fibrotic, four), usual interstitial pneumonia (two), organising pneumonia (two), lymphocytic interstitial pneumonia (one), and unclassifiable interstitial pneumonia (one). Nonspecific interstitial pneumonia was the most common histological pattern of interstitial pneumonia in patients with amyopathic dermatomyositis (three of three) and in patients with respiratory symptoms as the initial clinical manifestation of the connective tissue disease (three of four). Survival at 5 yrs was 50%. This study shows the clinician should remain alert to potential muscular or cutaneous manifestations whenever a pathological diagnosis of nonspecific interstitial pneumonia is made.

Adult↗
PubMed2003

[Respiratory manifestations of common variable immunodeficiency in adults].

INTRODUCTION: Sporadic common variable immunodeficiency (CVID) is the most frequent cause of primary humoral immunodeficiency observed in adults. Respiratory complications occur frequently. STATE OF ART: Recurrent bacterial pneumonia and bronchial suppuration are the most frequent complications whilst reactive interstitial pneumonitis (lymphoid interstitial pneumonia and sarcoid-like granulomatosis) and pulmonary lymphoma involvement are rarer. Treatment is based on replacement infusions of gamma globulin (Ig-IV). Although treatment has been shown to reduce the frequency of pulmonary infections, respiratory complications are still responsible for one third of late mortality in CVID. PERSPECTIVES: Type and frequency of respiratory survey has to be defined, as well as the indication for other treatments than Ig-IV. CONCLUSIONS: Protein electrophoresis must be done in a young adult with recurrent low respiratory tract infections and/or diffuse bronchectasis. Hypogammaglobulinemia should result in immunological and hematological investigations which may help to the diagnosis of CVID and to the beginning of the adequate treatment.

Adolescent↗
PubMed2002

Pyogenic bacterial lower respiratory tract infection in human immunodeficiency virus-infected patients.

In human immunodeficiency virus (HIV)-infected patients, bacterial lower respiratory tract infections are the most frequent respiratory diseases. They are frequently the first clinical manifestation of HIV infection. The incidence and severity of bacterial lower respiratory tract infections increase with the degree of immunosuppression. At the acquired immune deficiency syndrome (AIDS) stage, the responsible bacteria and clinical presentation may be atypical. Bacterial pneumonia may be fatal, particularly in AIDS patients, and its occurrence is predictive of a reduced survival time. Pneumococcal vaccine is recommended in patients with a CD4 T-lymphocyte count of > 200 cells mm(-3) and cotrimoxazole (trimethoprim/sulfamethoxazole) in patients with a CD4 T-lymphocyte count of < 200 cells x mm(-3). Unfortunately, such prophylaxis remains insufficiently prescribed and its protective effect is limited. Highly active antiretroviral treatment has dramatically reduced the incidence of lower respiratory tract infection due to Pseudomonas aeruginosa and opportunistic bacteria. In contrast, successful highly active antiretroviral therapy slightly decreased the risk of bacterial pneumonia due to usual bacteria, even in patients on successful highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed2002

Primary pulmonary lymphoma.

Three distinct entities are now covered by the definition of primary pulmonary clonal lymphoid proliferation. The aim of this review is to describe the pathophysiological, diagnostic, prognostic and therapeutic aspects of these three entities. Low-grade pulmonary B-cell lymphoma is the most frequent form of primary pulmonary clonal lymphoid proliferation. It arises from mucosa-associated lymphoid tissue. It is usually indolent and appears in the form of a chronic alveolar opacity. The prognosis is excellent, but treatment is controversial (simple monitoring, surgery or single-agent chemotherapy). High-grade pulmonary B-cell lymphoma is far rarer and usually occurs in individuals with an underlying disorder (e.g. immunodeficiency). The prognosis is poor and therapeutic options depend on the underlying disorder. The inclusion of lymphomatoid granulomatosis in the definition of primary pulmonary lymphomas is controversial. The clonal nature of the proliferation is very rarely demonstrated and extrapulmonary involvement is frequent (upper airways, skin, kidneys, central nervous system, etc.). The prognosis is extremely variable, with some authors reporting complete remission with steroids and cyclophosphamide and others reporting failure of combination chemotherapy.

Humans↗
PubMed2001

Spectrum of CD4 to CD8 T-cell ratios in lymphocytic alveolitis associated with methotrexate-induced pneumonitis.

The present study was conducted to confirm the presence of severe lymphocytic alveolitis and to determine the factors responsible for the very different alveolar CD4 to CD8 T-cell ratios (CD4/ CD8) described in methotrexate-induced pneumonitis (MTX-pneumonitis). Clinical and radiologic findings, as well as bronchoalveolar lavage (BAL) data, including CD4 and CD8 subset analysis, were retrospectively reviewed for patients hospitalized between 1985 and 2000 for MTX-pneumonitis. BAL cell counts from patients with MTX-pneumonitis (cases) were compared with those from patients receiving MTX but who did not have evidence of MTX toxicity (MTX-exposed patients) and those from healthy subjects (control subjects). Nineteen BAL were performed in 14 consecutive cases of MTX-pneumonitis. MTX was given for various underlying diseases. All cases presented a subacute diffuse interstitial pneumonitis that recovered, with MTX discontinuation and/or initiation of adjunctive steroid therapy. At the time of diagnosis, BAL cell counts in MTX-pneumonitis indicated severe lymphocytic alveolitis when compared with MTX-exposed patients and control subjects and moderate neutrophil alveolitis compared with control subjects. The lymphocytic alveolitis resulted from an increase in both CD4 and CD8 lymphocyte cell counts. Nevertheless, alveolar CD4/ CD8 T-cell ratios ranged from 0.4 to 9.6. CD4/CD8 values correlated positively with lymphocyte counts but negatively with time elapsed between last MTX administration and BAL and with steroid cumulative dose received by the patients. Severe lymphocytic alveolitis was confirmed in our series of MTX-pneumonitis. The between-patient variation in CD4/CD8 T-cell ratios may reflect the large range of time intervals between last MTX administration and BAL evaluation and the use of adjunctive steroid therapy.

Adolescent↗
PubMed2001

Acute respiratory failure following HAART introduction in patients treated for Pneumocystis carinii pneumonia.

Cases of paradoxical worsening of opportunistic infections shortly after the beginning of highly active antiretroviral therapy (HAART) prompted questions on the optimal timing of introduction of HAART in patients with inaugural AIDS-related opportunistic infections. We describe three cases of acute respiratory failure after early introduction of HAART in patients treated for Pneumocystis carinii pneumonia (PCP). The three patients had severe PCP that initially improved with anti-PCP and adjunctive steroid therapy. HAART was introduced 1 to 16 d after diagnosis of PCP, and steroids were stopped on Day 15. Seven to 17 d after HAART introduction, the three patients developed a second episode of severe acute respiratory failure with high-grade fever and patchy alveolar opacities on the chest roentgenogram. PCP resistant to cotrimoxazole, pulmonary superinfection, and drug-related pneumonitis were suspected but subsequently ruled out. Bronchoalveolar lavage and lung pathologic findings showed severe nonspecific pulmonary inflammatory foci surrounding a few persistent P. carinii cysts. All three patients recovered after HAART interruption or steroid reintroduction. We conclude that acute respiratory failure can recur after initiation of antiretroviral therapy in patients being treated for severe PCP. This phenomenon could result from rapid pulmonary recruitment of fully competent immune and inflammatory cells responding to a few persistent P. carinii cysts. A short course of steroid therapy may suppress this reaction.

AIDS-Related Opportunistic Infections↗
PubMed2001

The use of tetracyclines for the treatment of sarcoidosis.

BACKGROUND: To evaluate the safety and efficacy of minocycline in the treatment of sarcoidosis, a nonrandomized, open study was performed in patients with cutaneous sarcoidosis. OBSERVATIONS: Twelve patients with cutaneous sarcoidosis were treated with minocycline, 200 mg/d, for a median duration of 12 months. Three patients had extracutaneous lesions at the time of the study. The median follow-up was 26 months. A clinical response was observed in 10 patients, consisting of complete responses in 8 patients and partial responses in 2 patients. A progression of skin lesions was observed in 1 patient, and lesions remained stable in another patient. Adverse effects were minimal, except in 1 patient, who developed hypersensitivity syndrome. A slight hyperpigmentation occurred in 2 patients at the site of previous lesions, which completely disappeared after minocycline use was discontinued. A relapse of skin symptoms occurred after minocycline withdrawal in 3 patients, who further received doxycycline, 200 mg/d, allowing a complete remission of lesions. CONCLUSIONS: These results support that minocycline and doxycycline may be beneficial for the treatment of cutaneous sarcoidosis. Randomized controlled studies are warranted for the evaluation of the true efficacy of tetracyclines in these patients.

Adolescent↗
PubMed2001

Tumor-derived granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor prolong the survival of neutrophils infiltrating bronchoalveolar subtype pulmonary adenocarcinoma.

We evaluated the role of the tumor environment in the regulation of apoptosis of tumor-infiltrating neutrophils, the number of which correlates negatively with outcome, in patients with adenocarcinoma of the bronchioloalveolar (BAC) subtype. We examined three different parameters of apoptosis, namely morphological aspect, annexin-V expression, and DNA fragmentation. Bronchoalveolar lavage fluid (BALF) supernatants from patients with BAC significantly inhibited the 24-hour spontaneous apoptosis of normal peripheral blood neutrophils in vitro compared to BALF supernatants from control patients (64 +/- 4% versus 90 +/- 2% measured by annexin-V flow cytometry, P = 0.04). The alveolar neutrophil count correlated positively with the granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations in the patient's BALF. Furthermore, neutralizing antibodies (Abs) against GM-CSF and G-CSF significantly inhibited BALF anti-apoptotic activity (15 to 40% and 34 to 63% inhibition, respectively), whereas neutralizing Abs against interleukin (IL)-8, IL-6, IL-1beta and tumor necrosis factor-alpha had no significant effect. In an attempt to identify the cell origin of anti-apoptotic cytokines, we tested in vitro the effect of BAC cells (A549 cell line and primary culture derived from a patient's BAC tumor) on the apoptosis of peripheral blood neutrophils. Cell-free supernatants from tumor cells did not inhibit neutrophil apoptosis. In contrast, cell-free supernatants from tumor cells previously exposed to conditioned media from peripheral blood mononuclear cells and alveolar macrophages significantly inhibited spontaneous neutrophil apoptosis. This inhibition was partially lifted when conditioned media from mononuclear cells were previously treated with Abs against IL-1beta and tumor necrosis factor-alpha. As in vivo, neutralizing Abs against GM-CSF significantly inhibited the anti-apoptotic activity of cell culture supernatants, and combination with Abs against G-CSF had an additive effect. In vivo, GM-CSF and G-CSF were strongly expressed by tumor cells and moderately or not expressed by the normal epithelium, as assessed by immunohistochemical studies. These findings demonstrate that the tumor environment generates local conditions that prolong alveolar neutrophil survival through the production of soluble factors, thereby contributing to the persistence of the neutrophil alveolitis observed in BAC.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Bilateral phrenic paralysis in a patient with systemic lupus erythematosus.

Respiratory manifestations of systemic lupus erythematosus (SLE) are frequent. They include respiratory muscle abnormalities, which have been implicated in the pathogenesis of the "shrinking lung syndrome" (SLS). We report the case of a patient with this syndrome, in whom diaphragmatic paralysis due to demyelinating phrenic lesions was diagnosed at the same time as SLE. Follow-up studies showed a favorable clinical and diaphragmatic outcome with corticosteroid therapy, but little change in spirometry. It is concluded that severe diaphragm palsy is possibly due to phrenic nerve lesions in SLE, and that the link between diaphragm dysfunction and the SLS is probably not a straightforward one.

Adult↗
PubMed2001

AIDS-related alveolar hemorrhage: a prospective study of 273 BAL procedures.

STUDY OBJECTIVES: To evaluate the frequency and diagnostic significance of alveolar hemorrhage (AH) in HIV-infected patients. DESIGN: A 3-year prospective cohort study. SETTING: A university hospital in Paris, France. PATIENTS: Two hundred forty-three HIV-infected patients undergoing 273 BAL procedures during the study period. METHODS: AH was assessed by using the Golde score. Data on the patients treated and observed in our institution were collected, as well as on their survival rate 12 months after undergoing BAL. Risk factors for AH were sought by comparing patients with AH (cases) and those without AH (control subjects). RESULTS: AH frequently occurred but usually was subclinical and cytologically mild. AH did not alter the 12-month survival rate. AH always was associated with at least one specific AIDS-related pulmonary disorder, and the following four independent risk factors were identified in a stepwise forward logistic regression model: pulmonary Kaposi's sarcoma (KS; odds ratio [OR], 5.3; 95% confidence interval [CI], 1.8 to 16.7; p = 0.003), cytomegalovirus (CMV) pneumonia (OR, 9.8; 95% CI, 1 to 100; p = 0.05), hydrostatic pulmonary edema (OR, 16.4; 95% CI, 1.8 to 142; p = 0.01), and platelet count < 60,000 cells/microL (OR, 5.6; 95% CI, 1.5 to 20; p = 0.009). CONCLUSIONS: AH is frequently diagnosed during BAL in HIV-infected patients. Its presence may point to an underlying cause, such as pulmonary KS, CMV pneumonia, or hydrostatic pulmonary edema, or to triggering factors such as thrombocytopenia.

AIDS-Related Opportunistic Infections↗
PubMed2000

[Diagnostic approach in diffuse infiltrative lung diseases].

Infiltrative lung diseases (ILD) include more than 130 diseases. Chronic and acute forms of ILD must be differentiated. In each group, cases with a known cause or with an unknown cause have to be individualized. For the physician, the distinctive sign of ILD is the evidence of diffuse pulmonary opacities on chest X rays or a suggestive pattern on pulmonary function tests. The diagnosis of chronic ILD depends on epidemiologic data ("a priori" probabilities), anamnestic informations, clinical and radiological (radiography and tomodensitometry) findings which make possible to consider a diagnosis of high probability in at least 60% of cases and reduce the gamut of hypothesis in the others. Other investigations (blood, endoscopy, broncho-alveolar lavage and sometimes surgical lung biopsy) lead to the final diagnosis. Most frequent chronic ILD are sarcoidosis, idiopathic pulmonary fibrosis and connective disease associated ILD. In case of acute ILD, diagnostic procedures depend on the severity of the disease and symptomatic treatment is urgent. The main lung lesion is either oedema or alveolitis. Main acute ILD are respectively cardiogenic oedema, lesional oedema, intra-alveolar hemorrhage, infectious ILD and acute eosinophilic pneumonia. The diagnostic approach depends on the presence of an initial orientation. Sometimes, several causes are associated.

Acute Disease↗
PubMed2000

[Diffuse infiltrative lung diseases of infectious and neoplastic origin].

Among the causes of chronic diffuse infiltrative lung diseases, infection and neoplasia have to be suspected in priority because of their frequency and their therapeutic specificities. Diffuse infiltrative lung diseases related to infection, often acute and feverish, are due to Pneumocystis carinii pneumonia, miliary tuberculosis, or virus and atypical pneumonia. Strategy for microbiological diagnosis depends on the pathogen suspected and the pulmonary disease severity. By contrast, diffuse infiltrative lung diseases due to neoplasia, mostly chronic diseases, include lymphangitic carcinomatosis and more rarely diffuse bronchoalveolar carcinoma and lymphoproliferative diseases.

Adenocarcinoma, Bronchiolo-Alveolar↗