Isotretinoin-related eosinophilic pleural effusion.
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Biomedical subjects
Publications and source records attributed to G M Akoun.
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BACKGROUND: The aim of this study was to report the effects of a three-drug chemotherapy regimen in patients with symptomatic AIDS-related pulmonary Kaposi's sarcoma and to analyse prognostic factors for survival. METHODS: Thirty consecutive HIV seropositive patients with respiratory symptoms and proven pulmonary Kaposi's sarcoma were treated with the same therapeutic regimen comprising adriamycin (30 mg/m2), bleomycin (10 mg/m2), and vincristine (2 mg) administered intravenously once every four weeks. RESULTS: Two patients died during the first course of chemotherapy. In the other 28 cases dyspnoea improved and Pao2 rose despite minimal (n = 17) or no (n = 11) improvement in the chest radiographic appearance. The median survival from the beginning of chemotherapy was 6.5 months. Poor prognostic factors for survival were: (1) absence of cutaneous Kaposi's sarcoma; (2) previous opportunistic infection; (3) CD4 cell count < 100/microliters; (4) leucocytes < 3500/microliters; (5) haemoglobin < 10 g/dl; and (6) absence of radiological response. Of the 28 patients 24 experienced at least one episode of neutropenia which was associated with bacterial infection in 16 cases. CONCLUSIONS: Chemotherapy may improve respiratory impairment in patients with extensive pulmonary Kaposi's sarcoma but the outcome remains poor. The efficacy of chemotherapy may be limited by neutropenia.
Since chest X-ray and CT scan features of Kaposi's sarcoma (KS) are nonspecific, we wanted to test the hypothesis that the histological components of this tumour and/or the associated haemorrhagic component, may result in a characteristic signal pattern on magnetic resonance imaging (MRI). Thoracic MRI was performed in a prospective manner in ten patients with acquired immune deficiency syndrome (AIDS) and pulmonary KS. MRI examinations (1.5 Tesla) included Spin-echo T1 (SE-T1), before and after gadolinium injection, as well as T2-weighted sequences (SE-T2). For each sequence the signal intensity of lesions was measured and compared with each other as well as with the signal intensity of muscle. Results were compared to the hemosiderin content of macrophages in the bronchoalveolar lavage (BAL) in all patients and with histological findings in three. The results were compared to values obtained in a control group of seven patients with pneumocystis carinii pneumonia. SE-T1 showed focally increased signal intensity in the pulmonary parenchyma (n = 5). Signal enhancement in parenchymal lesions (n = 10) and along peribronchovascular trees (n = 5) was observed after gadolinium injection. The second echo of SE-T2 showed a markedly reduced signal intensity in pathologic areas (n = 10). This last finding was not observed in the control group. In conclusion, we have identified a pattern of MRI signal abnormalities suggestive of Kaposi's sarcoma. The MRI signal intensity of KS lesions may be related to the angiomatous and fibrous components of the tumour.(ABSTRACT TRUNCATED AT 250 WORDS)
STUDY OBJECTIVE: This prospective study was performed in an attempt to evaluate (1) the rate of magnetic resonance imaging (MRI) demonstrating bone marrow (BM) abnormalities, (2) the correlation of these abnormalities with a pathologic malignant BM involvement, and (3) the possible modification of patients' usual disease staging in the light of these abnormalities. METHODS: After extensive staging investigations, patients' diseases were classified as limited or extensive. Dorsal and lumbar spine MRI was performed for second staging. RESULTS: Thirty-two patients were eligible for this study. In ten patients (31.2 percent), MRI showed abnormalities; in four of them, the BM sample from the posterior iliac crest was free from malignancy. Three of these four patients had extensive disease. The last patient, because he had limited disease, had biopsy at the site of MRI abnormalities; the biopsy specimen revealed a malignant involvement and therefore this patient, initially classified as having limited disease, was classified in the extensive disease group. In only 1 of 32 patients, BM-MRI data modified initial staging. CONCLUSIONS: The metastases disclosure yield of the MRI in the detection of medullar involvement is higher than BM biopsy but especially in patients with extensive disease. Therefore, MRI should not be considered in routine practice, in particular in patients with extensive disease.
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Over the past ten years, there has been an impressively growing number of reports about drug-induced pneumonitis (DIP) due to more than one hundred different drugs. The most troublesome question is how to establish with certainty the diagnosis. Usually, five criteria are necessary. 1) The administration of a drug on a more or less long term basis. 2) Newly occurrence of an interstitial pneumonitis (defined on symptomatology, radiological features, pulmonary function test results). 3) Elimination of all other causes of pneumonitis (haemodynamic, infectious, systemic, environmental diseases). 4) Broncho-alveolar lavage (BAL) cell data showing in most cases a lymphocyte alveolitis with an inverted CD4/CD8 ratio. In a certain number of ambiguous circumstances, coupling a provocation test with a sequentially performed BAL could firmly establish the diagnosis. 5) Rapid resolution within a few days or months of the pneumonitis as early as the incriminated drug administration is stopped. Nevertheless sometimes one or more of these criteria are not met, mainly when the pneumonitis is a fibrosis directly induced by a fibrosing toxic mechanism.
A 20-yr-old woman with chronic liver disease and angioimmunoblastic lymphadenopathy presented with marked hypoxemia caused by intrapulmonary shunt. Her respiratory tract showed her to be free of angioimmunoblastic lymphadenopathy manifestations. After 12 months of treatment with cyclophosphamide and corticosteroid, the immunologic disease disappeared. Unexpectedly, hypoxia-associated intrapulmonary shunt was no longer present either. To the best of our knowledge, this is the first case of dramatic improvement, with medical therapy, of severe hypoxemia related to noncirrhotic liver disease. However, the mechanism by which this treatment caused the regression of intrapulmonary shunt is unknown.
Broncho-alveolar lavage was performed to assess the degree of pulmonary lymphocytic alveolitis in 32 asymptomatic patients who were infected with the Human Immunodeficiency Virus (VIH). The patients were stages II and III of the CDC classification and the aim of the study was to determine the frequency, nature and prognostic role of the findings. 62.5% of the subjects (20/32) presented with a lymphocytic alveolitis which consisted predominantly of CD8 lymphocyte (64.3 +/- 3.5%), in the absence of an opportunistic infection or broncho-pulmonary tumours. Two sub-populations of alveolar CD8 were shown at comparable levels, a) sub-population CD8+D44+ (22.1 +/- 5%), in whom we showed the possession of cytotoxic activity in particular specific for VIH; b) sub-population CD8+CD57+ (19.6 +/- 3%) which we have shown to be capable in vitro of inhibiting the effector phase of cytotoxic activity of CD8+D44+ alveolar cells specific for VIH. In this group of 32 patients the occurrence of an alveolitis was not correlated with the usual prognostic factors of infection by VIH measured simultaneously with broncho-alveolar lavage (the level of CD4+ blood lymphocytes, and the beta 2-plasma microglobulins and the presence of p24 antigenaemia). In addition the level of CD4 lymphocytes supperior to 400/mm3 and of beta 2-microglobulins less then 3 mg/l whether a lymphocytic alveolitis was there or not confirmed the relatively poorly developed state of the VIH infection in these asymptomatic patients. Also the occurrence of a lymphocytic alveolitis did not seem to be linked to progression of the disease in the group of patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)
The leukocyte migration inhibition test (LMIT) was performed in 8 cases of presumed drug-induced pneumonitis. The drugs involved were amiodarone in 3 cases, methotrexate in 2 cases, and fenofibrate, nadolol, and gold salt, each in one case. The agarose microdroplet technique for photoelectric readings of leukocyte migration inhibition was applied in the presence of a wide range of drug concentrations. LMIT was found to be positive in 6 of the 8 cases (75%). The presence of a positive LMIT indicates the elaboration of leukocyte migration inhibitory factor. These results suggest that cell-mediated immunity may play a role in the pathogenesis of drug-induced pneumonitis and that LMIT may be useful for the detection of causative drugs in patients with this condition.
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In bronchoalveolar lavage fluid (BAL) from nine patients with alveolar proteinosis (AP), total and differential cell count and T-lymphocyte phenotyping were done and compared with those in 12 healthy volunteers comparable as to age and tobacco consumption. Although total cell count was not significantly different from that in control subjects, the most prominent feature in patients was an increase in the number of CD4 and CD8 T-lymphocytes within the alveoli. Conversely, the macrophage population was significantly reduced. The ratio of CD4/CD8 T-lymphocytes tended to be high, but this increase did not reach statistical significance. The pathophysiologic mechanism and the meaning of these alveolar cell changes in AP remain to be elucidated.
We examined bronchoalveolar lavage (BAL) cell data from 19 patients with a lung disorder presenting clinical, radiologic, functional, and course characteristics of drug-associated interstitial pneumonitis. In each of them, one of 13 different drugs was incriminated and no other cause was found. In one case due to bleomycin, a neutrophil and eosinophil alveolitis was present. In the other 18, the common denominator was a lymphocyte alveolitis, either pure (n = 6) or associated with neutrophilia (n = 5), eosinophilia (n = 3), or neutrophilia and eosinophilia (n = 4). In addition, in all patients, an inverted CD4/CD8 lymphocyte ratio was observed. In eight patients who underwent another BAL, lymphocyte alveolitis decreased but was persistent in two of them two to four months after cessation of treatment with the drug incriminated, whereas interstitial pneumonitis had resolved clinically. In five patients, after resolution of pneumonitis and after an almost normal BAL cell profile was obtained, resumption of treatment with the suspected drug for two to four weeks induced a rise in lymphocyte population in a third BAL. In conclusion, apart from one case of bleomycin lung, the most striking feature of drug-associated alveolitis in this series was expansion of lymphocyte population and imbalance in lymphocyte subsets. When a provocation test was performed, variations in alveolar lymphocyte levels paralleled withdrawal and readministration of the drug responsible for alveolitis. These data could be of value in diagnosing and understanding drug-induced lung disorders.
To assess the value of bronchoalveolar lavage (BAL) for diagnosis, understanding, and treatment of amiodarone-associated pneumonitis, we examined the results of BAL total and differential cell counts and phenotyping of lymphocytes in 22 patients with this lung disorder and in 33 normal subjects. Overall, the total cell count was found to be almost the same as that seen in control subjects; the macrophage population was significantly reduced, and the lymphocyte, neutrophil, and eosinophil populations were increased in absolute number and percentage. When results were analyzed individually, BAL data appeared to be distributed according to two patterns. In the first pattern, there was no abnormal lymphocytosis. In the second pattern a lymphocyte alveolitis was found in percentage and in absolute number. This lymphocyte alveolitis was present either alone or associated with neutrophil alveolitis or with eosinophil alveolitis. In the first pattern, despite the normal level of the lymphocyte population, the percentage of CD4 T-lymphocytes and the CD4:CD8 T-lymphocyte ratio were significantly lowered. In the second pattern the CD8 T-lymphocyte count was increased in absolute number and percentage, with a low CD4:CD8 ratio. In six patients relavaged two to four months after amiodarone withdrawal, there was a significant fall in alveolar lymphocytosis, but the progressive increase in the neutrophil population over time seemed to be associated with the seriousness and progression of the disease. Finally, these findings closely resembled those obtained in patients with hypersensitivity pneumonitis due to inhalation of organic dust and suggest that an underlying immunologic cell-mediated mechanism may play a role in this iatrogenic pulmonary disease.
Mycobacterium szulgai is a newly recognised species of mycobacteria whose pathogenicity in man can only be confirmed following certain criteria. We report a new observation comprising three points of interest. M. szulgai appears to be directly responsible for pulmonary infection and the clinical and radiological progress is very rapid. The human disease probably comes from infected water in aquaria. We have reviewed other cases of M. szulgai in the literature and for two out of three amongst these there is pulmonary involvement resembling tuberculosis; in the other cases cutaneous disease, synovial disease and bone disease have been described.
In an attempt to evaluate the diagnostic help of bronchoalveolar lavage cell data in drug-induced pneumonitis (D.I.P.), we collected through the world literature 167 cases of D.I.P. In 122 cases, data were available for individual analysis (68 associated with amiodarone prescription and 54 with other drugs). 28 drugs were incriminated. Apart from 13 cases with normal BAL cell profile, the most prominent feature in the other 109 was a lymphocyte alveolitis either pure or associated with neutrophil and/or eosinophil alveolitis along with an imbalance in T-lymphocyte phenotype. These characteristics closely resembled those observed in hypersensitivity pneumonitis due to inhalation of organic dust. Nonetheless, about one third or more of cases displayed no lymphocytosis but neutrophil and/or eosinophil alveolitis. Taken together, these findings are in no way specific for D.I.P. but could be of interest to help diagnosis and understanding of iatrogenic alveolitis, especially when a provocation test coupled with sequential BAL is performed.
About 20 cases of beta blocker-associated pneumonitis have been published in the mid-70s, and a case of interstitial pneumonitis has been attributed to propranolol. The pathogenesis of these cases of pneumonitis with or without pleural effusion is not clear. A 59-year-old man developed pneumonitis which showed all the characteristics of a drug-associated pneumonitis due to propranolol: BAL demonstrated a lymphocytosis, the variations of which closely correlated with a provocation test. The LIF appeared to be released by the patient's peripheral blood lymphocytes when cultured with optimal doses of propranolol. Production of LIF by the patients' lymphocytes suggests the existence of a drug-specific cellular immune response in propranolol-associated pneumonitis.
A 79-year-old man was given a cumulative dose of 16.5 g of nilutamide for treatment of prostate cancer. He then presented with a respiratory illness having clinical, radiologic and functional characteristics of interstitial pneumonitis. No other cause of pneumonitis was found. Bronchoalveolar lavage showed a lymphocytic alveolitis with an inverted lymphocyte subset ratio. After an 11-week period of drug withdrawal, clinical, radiologic and functional improvement was observed along with a normal alveolar lymphocytosis. Nilutamide therapy was then resumed for five weeks and induced the recurrence of clinical, functional and alveolar abnormalities. Nilutamide treatment was finally stopped and two months later, clinical and functional abnormalities resolved. This observation seems to exemplify the possible diagnostic value of coupling provocation test with BAL cell data in hypersensitivity pneumonitis induced by drugs. In addition, these data support the role of a cell-mediated immunologic mechanism in the pathogenesis of nilutamide-induced pneumonitis.
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