Biomedical subjects

G Ferretti

Publications and source records attributed to G Ferretti.

At least 307 records · Page 17Linked to original sources

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Cisplatin and vinorelbine as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) resistant to taxol plus gemcitabine.

The aim of the study was to evaluate the activity of cisplatin (CDDP) plus vinorelbine (VNR) in patients with advanced non-small cell lung cancer (NSCLC) progressing after paclitaxel plus gemcitabine. Treatment consisted of CDDP 80 mg/m(2) administered on day 1 and VNR 25 mg/m(2) administered on day 1 and 8, repeated every 3 weeks. Nine patients who relapsed after partial response and eight patients refractory to prior CT received a minimum of two treatment cycles: three patients achieved a PR (18%; 95% CI: 4-43%), four had stable disease and 10 had disease progression. All responses were observed among the nine patients responsive to prior treatment. Median survival was 35 weeks. No patients required dose-reduction, treatment discontinuation or delay because of toxicity. Our results indicate a reasonable antitumor efficacy and no relevant toxicity of a second-line CDDP-based chemotherapy in patients with advanced NSCLC. We recommend the use of this regimen for patients not refractory to primary treatment.

Adult↗

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[Systemic air embolism after CT-guided transthoracic biopsy using a cutting needle].

The authors report a case of systemic air embolism after CT-guided transthoracic needle biopsy using an 18G cutting needle. CT performed immediately after the occurrence of neurological signs showed air within the left ventricle but no air within the cerebral arteries. Radiologists must be aware of this extremely rare but potentially severe complication to provide accurate diagnosis and treatment.

Biopsy, Needle↗

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Dramatic regression of multiple brain metastases from breast cancer with Capecitabine: another arrow at the bow?

Several chemotherapic agents, which are active against breast cancer, penetrate poorly into the central nervous system. Despite its limited brain penetration, 5-fluorouracil has been a component of effective regimens for brain metastases. Capecitabine is a recently developed oral prodrug that is converted into 5-fluorouracil by sequential enzymatic steps. Thymidine phosphorylase (TP) is the final enzyme responsible for Capecitabine activation. Studies have demonstrated that high intratumoral levels of TP and low levels of its catabolite dihydropyrimidine-dehydrogenase are correlated with the capecitabine response. The penetration of Capecitabine across the brain-blood barrier remains unknown; we report the case of and discuss a breast cancer patient who had an interesting response of brain metastases with Capecitabine in monochemotherapy before brain irradiation.

Adult↗

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Plasma membrane fluidity in isolated rat hepatocytes: comparative study using DPH and TMA-DPH as fluorescent probes.

The study of membrane fluidity is a rapidly expanding field of research and its interest in hepatology has been stressed recently. The present study is the first report concerned with the determination of membrane fluidity of isolated rat hepatocytes. The data have been compared with those obtained in plasma membrane fractions and subfractions (basolateral or canalicular) derived from homogenates. The fluorescent probes used to measure the fluidity were diphenylhexatriene (DPH) a 'classical' probe, and its derivative trimethylammoniodiphenylhexatriene (TMA-DPH) at 25 degrees C and at 37 degrees C. The values obtained with DPH were lower than those with TMA-DPH, probably due to the localization of the probes in different regions of the phospholipid bilayer. In addition, DPH revealed significant differences in the fluorescence polarization values obtained in isolated hepatocytes compared with membrane fractions, which was in contrast to TMA-DPH, where the respective values were of the same order of magnitude. This behaviour is probably due to the mobility of DPH in the membrane core and its rapid internalization into the cell, whereas TMA-DPH remains anchored for a long time on the cell surface. These findings suggest that TMA-DPH is a better probe than DPH for measuring the fluorescence polarization of whole isolated hepatocytes and that the use of different probes might be of help in exploring different zones of the membrane bilayer.

Animals↗

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Azelastine in the prophylactic treatment of bronchial asthma: an Italian multicentre comparison with ketotifen.

The prophylactic effectiveness of the phthalazinone derivative, azelastine was compared with ketotifen. A total of 111 patients, aged 18-65 years, from 10 centres was entered into this randomized, double-blind study. All patients had reversible asthma. After 1 week on placebo, patients were allocated to either 8 mg/day azelastine once or twice daily, or to 1 mg ketotifen, twice daily, for a further 12 weeks. Azelastine was more effective in improving respiratory function (forced expiratory flow in 1 s and peak expiratory flow rate) when given in the once daily regimen, whereas clinical measures (number of weekly asthma attacks) were most improved by twice daily dosing. There was no significant difference between the effectiveness of azelastine and that of ketotifen. Treatments were equally well tolerated and a low incidence of side-effects was reported. In conclusion, 8 mg/day azelastine, in either a single or twice daily dosage regimen may be regarded as providing effective prophylaxis against bronchial asthma.

Adult↗

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Effect of Ca2+ on structure and fluidity of microvillus membranes of human placenta.

This investigation shows the effect of a Ca2+ addition on the structural and physiochemical properties of microvillus plasma membranes obtained from human placenta. Ca2+ addition induces an increase in microviscosity, as shown by the increase of order parameter and rotational correlation time of 5- and 16-doxylsterate derivatives and by the increase of fluorescence polarization of diphenylhexatriene. All the effects were obtained in a wide temperature range. The morphometric analysis of the ultrastructural images shows that the vesicle profiles of syncytiotrophoblast membranes decrease both area and form factor (FF) in the presence of Ca2+ with respect to the controls. The freeze-fracture results also show that Ca2+ induces an enhanced tendency to IMP clusterization. The Ca2+-induced changes were observed in both E and P faces. Our results underline the important role of Ca2+ in the cell membrane structure per se and in modulating interactions between cytoplasmic and extracellular microenvironments. The results of morphometric analysis of the ultrastructural images agree with biochemical data showing an increased stability induced by calcium on plasma membranes.

Calcium↗

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Properties of a phosphatidylcholine derivative of diphenyl hexatriene (DPH-PC) in lymphocyte membranes. A comparison with DPH and the cationic derivative TMA-DPH using static and dynamic fluorescence.

Using static and dynamic fluorescence we studied the fluorescence properties of a phosphatidylcholine analog of 1,6-diphenyl-1,3,5-hexatriene (DPH-PC) incorporated in lymphocyte plasma membranes with respect to DPH and its cationic derivative 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), in order to study if phospholipid derivatives of DPH may be used to investigate structural and physicochemical properties of specific membrane lipid domains. DPH-PC and TMA-DPH showed similar fluorescence polarization values that were significantly higher with respect to DPH, suggesting a localization of the fluorescent portion of DPH-PC in a more ordered region of the membrane which was probably due to the elecrostatic interactions between phospholipid head-groups. The localization of the fluorescent moiety of DPH-PC near the membrane surface was also supported by the study of the fluorescence decay of the three probes using frequency-domain fluorometry. The main lifetime component of DPH-PC was rather similar to that of TMA-DPH (6.74 versus 6.24, ns) but considerably lower with respect to DPH (10.52 ns), in agreement with data obtained from exponential analysis. In lymphocyte membranes obtained from concanavalin A treated cells, a significant decrease of fluorescence polarization has been shown with DPH and its phosphatidylcholine derivative, but not with TMA-DPH. In liposomes obtained from total lipids extracted from lymphocyte membranes, a decrease of fluorescence polarization has been observed only with DPH. Our results suggest that DPH-PC localizes the fluorescent portion of its molecule in membrane microenvironments of different properties with respect to those probed by DPH and TMA-DPH. The use of DPH-phospholipid derivatives and other DPH-probes may represent an useful tool to study plasma membrane heterogeneity in biological membranes.

Animals↗

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Analysis of 4-ABP-DNA adducts and p53 alterations in urinary bladder carcinoma.

BACKGROUND: Activated intermediates of 4-aminobiphenyl (4-ABP) are able to covalently interact with DNA to form adducts. There is a large body of evidence indicating that carcinogen-DNA adduct formation can be one of the cancer initiating mechanisms. MATERIALS AND METHODS: (4-ABP)-induced DNA damage in association with p53 overexpression and mutations were evaluated in specimens of urothelial bladder cancers from 106 patients. RESULTS: 4-ABP-DNA adduct levels resulted higher in smokers compared to non smokers, with a borderline statistical value. p53 nuclear overexpression was related to tumor grading, while no significant correlation with stage, 4-ABP-DNA adducts, smoking habit, and disease recurrence could be observed. Concerning molecular analysis, p53 point mutations were found in 17 of 106 cases (16%) and mutational pattern was significantly associated both with higher grade and stage, but no correlation was found with disease recurrence. CONCLUSIONS: These results suggest that other sources, in addition to tobacco smoke, may contribute to 4-ABP-DNA adducts formation in bladder tissue and that p53 expression/mutation cannot be considered a prognostic factor in bladder cancer.

Aminobiphenyl Compounds↗

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[An occult pancreatic insulinoma: radio-guided surgery with 111-In-octreotide. A case report and review of the literature on pre- and intraoperative diagnosis].

INTRODUCTION: Pancreatic insulinoma is a small, rare neoplasm; its radical therapy is surgical enucleation or resection. Although clinical diagnosis is simple, instrumental and radiological localization is still difficult (occult insulinoma: 10-20%). MATERIAL AND METHODS: The authors present the case of a 71-year-old patient suffering from relapsing vertigo syndrome, derangement and transient lypothymia after strong physical activity. ECG, encephalic and abdominal C.T., eco-color-Doppler of epiaortic vessels failed to identify any pathological features. Laboratory tests only revealed that basal glycemia was always lower than normal. Insulinoma was strongly suspected following the outcome of dosages of insulin and C-peptide in the serum and was confirmed after a supervised fast test (72 h). Once the biochemical diagnosis had been reached an abdominal eco, C.T., a selective and superselective angiography and echo-endoscopy were carried out to locate the tumor site but results were negative. Only somatostatin-receptor scintigraphy with 111 In-octreotide detected a catchment area (diameter: 3 cm) to the right of the hypochondrium, anterior to the kidney and caudal to the left hepatic lobe. RESULTS: During laparotomy a hand-held gamma detecting probe (C-Trak) was used to detect in situ tumour binding of the radiolabelled octreotide and a neoplasm was identified and enucleated from the pancreatic head (diameter: 7 mm), undistinguishable from the surrounding parenchyma. Postoperative signal checks of the surgical field and of the neoplasm revealed, in the first, the absence of captation and, in the second, maximal captation. Histological findings confirmed the nature of the neoplasm: an insulinoma with a ring pattern. Two years after surgery the patient is in good health, with no signs of relapse. CONCLUSIONS: Radio-guided surgery with labelled octreotide makes it possible to pinpoint small insulinomas, locate occult neoplasm, verify the completeness of surgical excision in the field and in the surgical piece, by comparing the different captation of labelled octreotide and check neoplasm multicentricity and any metastases.

Aged↗

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Effect of tamoxifen on GH and IGF-1 serum level in stage I-II breast cancer patients.

OBJECTIVE: Tamoxifen suppresses insulin-like growth factor-1 (IGF-1) plasma levels in early and advanced breast cancer patients. Relationships between tamoxifen (GH) and IGF-1 are complex and not completely described yet. The present investigation was performed to evaluate the effect of acute and chronic tamoxifen administration on GH response to growth hormone-releasing hormone (GHRH), as well as on IGF-1 serum levels. MATERIALS AND METHODS: Evaluation of GH after administration of GHRH was performed (a) at baseline, (b) 3 hours after 20 mg oral administration of tamoxifen and (c) after 12 weeks of 20 mg a day oral tamoxifen treatment, in fifteen postmenopausal stage I-II breast cancer patients. IGF-I was measured at baseline and after chronic tamoxifen administration. RESULTS: The GH response to GHRH was significantly reduced after 12 weeks of tamoxifen 10 mg administered twice a day orally (mean peak 3.2 +/- 0.2 micrograms/l, mean AUC 261.3 +/- 18.2 micrograms/minute p < 0.01 versus basal AUC). A concomitant significant reduction of IGF-1 was observed after 3 months of tamoxifen treatment. Basal pretreatment levels of 113.2 +/- 15.5 micrograms/l were suppressed to 70 +/- 7.9 micrograms/l (p < 0.01). CONCLUSION: Our study confirm the inhibitory effect of tamoxifen on IGF-I and suggested, as shown in previous in vitro data, that its suppression could be directly related to GH reduction in response to GHRH stimulation.

Aged↗

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Sestamibi scintimammography in pT1 breast cancer: alternative or complementary to X-ray mammography?

The aim of this study was to compare the results obtained using X-ray mammography (MG) and 99mTc-sestamibi scintimammography (SSM) in patients with breast lesions < or = 2 cm. One hundred and thirty-four women (median age 52 years, range 32-78), who had already been selected for open breast biopsy, underwent both MG and SSM prior to surgery. Final pathology showed 27 (20.1%) benign breast lesions and 107 (79.9%) breast cancers (pT1a=5 [4.7%], pT1b=50 [46.7%], pT1c=52 [48.6%]). The sensitivity, positive predictive value, negative predictive value and accuracy were 81.3%, 97.6%, 55.6% and 83.6% for SSM and 83.2%, 89.9%, 48.6% and 79.1% for MG, respectively. The results were similar (p=NS), but patients with breast cancer (BC) undetected by MG were significantly (p<0.05) younger than those in which the tumor was correctly diagnosed, while the age did not affect SSM sensitivity. SSM was more (p<0.05) specific than MG in BC detection both in the overall group of patients (92.6% vs 63.0%) and in those with < or = 10 mm breast lesions (94.7% vs 63.2%). In conclusion, in patients with suspected BC sized < or = 2 cm, SSM may help in surgical planning because of its high specificity, and should be considered complementary to MG, especially in younger women.

Adult↗

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Diagnosis of T1 bladder transitional cell carcinoma by denaturing gradient gel electrophoresis urinalysis.

OBJECTIVE: The diagnosis and follow-up of patients with T1 bladder cancer relies invasive procedures. We developed a non-invasive method for detection of T1 bladder cancer based on a feasible non-radioactive molecular approach. MATERIALS AND METHODS: Urine DNA samples were collected from 24 patients with T1 transitional cell carcinoma (TCC) of the bladder and were processed by denaturing gradient gel electrophoresis (DGGE) analysis. Urine samples obtained from 10 individuals with no clinical evidence of genitourinary malignancy were used as controls. RESULTS: Ten patients out of 24 (41%) had p53 mutations in their tumor samples. Seven of these presented the same mutation in matched urine samples. The p53 mutation pattern found in urine was always identical to that identified in the primary tumor. Decision diagnostic criteria showed that molecular screening by DGGE of amplified DNA from urine sediment had 69.2 % sensitivity, 100% specificity, 95.8 % accuracy, 100% prediction of positive result and 95.4 % prediction of negative result, respectively. No p53 mutation was found in the urine from control subjects. CONCLUSION: DGGE analysis of urine samples could be a useful tool for the early detection of T1 bladder cancer or its recurrence, potentially leading to a reduction in the frequency of invasive procedures used for the management of this disease.

Aged↗

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Huge response to letrozole in inoperable T4 breast cancer: a case report.

A 73 years-old woman presented with locally advanced breast cancer (cT4b cN1 M0, stage IIIB) and atrial flutter. Because of the arrhythmia, chemotherapy or tamoxifen, although malignancy was hormone-sensitive, were discarded. Letrozole was started. Two months later, the breast nodule and skin ulceration cleared up. Surgery was performed. Nowadays, 24 months later, patient does fine, continuing letrozole as adjuvant treatment.

Aged↗

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GSTM1, P53 and K-ras molecular detection in resectable non-small cell lung cancer by denaturing gradient gel electrophoresis-bronchoalveolar lavage fluid analysis.

BACKGROUND: Understanding molecular abnormalities could potentially lead to novel investigational approaches in the molecular epidemiology of lung cancer. These might include the identification of patients at high risk for primary NSCLC and the surveillance of patients with known NSCLC who are being treated using lung-sparing surgical strategies. MATERIALS AND METHODS: The PCR-Denaturing Gradient Gel Electrophoresis (DGGE) strategy was used for primary tumors and corresponding bronchalveolare lavage (BAL) samples. RESULTS: We recruited 36 consecutive patients with NSCLC, 28 (77.7%) males and 8 females (22.3%). DGGE showed a good rate of accuracy in the genetic screening of K-ras and p53 mutations in BAL specimens. Specific mutations were more often detected in BAL fluid from patients with not peripheral tumors than parenchymal or peripheral tumors (p53: 85.7%, p=0.0004; K-ras: 75%, p=0.001). p53 mutations were more frequent in BAL fluid from squamous cell carcinomas (22%) than from adenocarcinomas (15%). A significant correlation was observed between null GST-Ml genotype and p53 overall mutations (p=0.0003), K-ras mutations (p=0.02), non peripheral tumors (p=0.04) and smoking habits (p=0.002). CONCLUSIONS: We observed that null GSTMl genotype is strongly related to p53 mutations. Individuals at high risk for primary NSCLC, such as heavy smokers or individuals exposed to occupational carcinogens, could be screened by BAL-analysis for cancer biomarkers of susceptibility like GSTM-1 in large scale molecular epidemiology studies.

Aged↗

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Chemotherapy with vinorelbine, cisplatin and continuous infusion of 5-fluorouracil in locally advanced breast cancer: a promising low-toxic regimen.

Primary chemotherapy for locally advanced breast cancer, usually an anthracycline-containing regimen, improves local disease control allowing for an initially inoperable tumour to be resected. The feasibility and efficacy of a regimen containing vinorelbine (V), cisplatin (P) and 5-fluorouracil (5-Fu) as continuous infusion (ViFuP regimen) for patients with locally advanced breast cancer were evaluated. Twenty-six patients with a T4 breast cancer presentation (eight also had synchronous distant metastases) were treated with V (20 mg total dose i.v. on day 1 and day 3), P (60 mg/m2 i.v. on day 1) and 5-Fu (200 mg/m2/d as continuous infusion) all given every 3 weeks for a maximum of 6 courses. Eleven patients had an inflammatory breast lesion, 4 had a T4a and 11 a T4b presentation. Among those with metastases, 6 had one site and 2 had two sites of disease. After chemotherapy all tumors except one became operable. Objective response was observed in 19 out of the 26 evaluable patients (73%; 95% CI: 52-88%): fourteen had a partial response (54%); 5 had a clinically complete response (19%) and 5 had complete pathological response (20%; 95% CI: 7-41%). Seven patients had stable disease (27%) while no disease progression under treatment occurred. Mild or moderate side-effects included neutropenia (G1-G2 in 58% and G3 in 31% of patients), anemia (G1 in 19%), nausea and/or vomiting (G1-G2 in 92% of patients), mucositis (G1-G2 in 23%), diarrhea (G1 in 19%), plantar-palmar erythema (G1 in 12%) and alopecia G1 in 27% of patients. We conclude that the ViFuP regimen is well-tolerated and its use results in a high response rate. Thus ViFuP may be considered a relevant alternative to more toxic regimens, with an acceptable response rate. Despite the lack of a formal demonstration of equal efficacy with more toxic regimens commonly applied in locally advanced breast cancer, testing new modalities or drugs might provide a more fruitful strategy for relevant therapeutic progress.

Adult↗

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Iatrogenic gastroduodenal ulcers during hepatic intra-arterial chemotherapy.

BACKGROUND/AIMS: Various percentages of iatrogenic gastroduodenal ulcers during hepatic intra-arterial chemotherapy have been reported in the literature. The aim of this study was to analyze a homogeneous cohort of patients in order to evaluate the evolution and management of this complication. METHODOLOGY: We retrospectively reviewed the clinical charts of 80 patients with primary or metastatic liver tumors who received 186 hepatic arterial infusion chemotherapy courses of 5-fluorouracil, cisplatin and mitomycin-C. All of the patients complaining of upper gastrointestinal symptoms during or after hepatic arterial infusion underwent esophagogastroduodenoscopy. RESULTS: Esophagogastroduodenoscopy was performed in 14 patients, all of whom had gastroduodenal ulcers. Two of ten investigated patients were Helicobacter pylori positive. All of the patients were treated with a proton pump inhibitor and five also received major analgesics. All of the ulcers healed without complications. Six patients did not continue with hepatic arterial infusion for reasons other than ulcers. Eight patients received a subsequent hepatic intra-arterial chemotherapy course, five despite the persistence of an active ulcer. CONCLUSIONS: Iatrogenic gastroduodenal ulcers are probably due to ischemia and the direct toxicity of the anticancer agents. They are Helicobacter pylori independent and do not represent an absolute contraindication for the continuation of hepatic intra-arterial chemotherapy.

Aged↗

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Hepatic intra-arterial chemotherapy using a percutaneous catheter in pretreated patients with metastatic colorectal carcinoma.

BACKGROUND: Hepatic intra-arterial chemotherapy (HIAC) leads to a higher response rate than systemic administration in untreated patients with liver metastases from colorectal cancer (CRC). The aim of this study was to evaluate the activity and safety of giving HIAC through a percutaneous catheter in pre-treated patients. PATIENTS AND METHODS: Forty-five CRC patients with liver-only or liver-dominant metastases, resistant or refractory to previous systemic therapy, were treated using a temporary trans-subclavian catheter. A 3-day chemotherapy regimen of daily 5-fluorouracil (5-FU) 1000 mg/m2/day + heparin 5000 IU/day given as a 24-hour continuous infusion, and twice daily bolus injections of cisplatin (CDDP) 10 mg/m2 and mitomycin C (MMC) 2 mg/m2, was administered every six weeks. RESULTS: One hundred and seventeen courses were administered to 45 patients (a median of three per patient: range 1-5). Of the 44 patients evaluable for response, 16 (35%) had a partial response, 15 (33%) stable disease and 12 (26%) progressive disease. Eleven of the 16 responding patients had been refractory to a previous 5-FU-based systemic therapy. The most relevant grade 3-4 toxicities included neutropenia (22%) and thrombocytopenia (15%). Gastro-duodenal ulcers occurred in nine patients. Catheter displacement was recorded during 22 out of 117 (18%) courses. CONCLUSION: HIAC with 5-FU, CDDP and MMC given through a temporary percutaneous catheter is safe and active in pretreated patients with metastatic CRC. Iatrogenic gastroduodenal ulcers are a serious but manageable complication.

Adult↗

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[Pleural fibrosis in asbestosis and ventilatory function: a study of 50 cases].

The importance of non-malignant pleural fibrosis in asbestosis in relation to respiratory function is still open to debate because of the differing results obtained in studies of different population groups. In the present study we selected 50 subjects with occupational exposure to asbestos presenting mono- or bilateral pleural fibrosis at X-ray but without lung impairment. Each subject underwent bronchial lavage and ventilatory function tests. The subjects were divided into 4 groups on the basis of the degree of pleural alterations according to the ILO Classification of Pneumoconioses. The results revealed that the mean values of CV and FEV1 in each group were within physiological limits. Moreover, analysis of the type of lung function showed a normal situation in 64% and restricted function in 28% of the cases. The prevalence of the latter finding was not correlated to the severity of pleural fibrosis in the various groups. Also, comparison between severity of pleural fibrosis and number of asbestos bodies/ml of BAL liquid on the one hand and frequency of alveolitis on the other did not reveal any relationship. Therefore, the onset of pleural fibrosis appears to be independent of the quantity of inhaled asbestos fibres and due to different mechanisms from those leading to lung fibrosis. In practice, a correct interpretation of the presence of pleural fibrosis from a clinical and prognostic viewpoint also requires other investigations such as BAL and a complete respiratory function study.

Adult↗