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Biomedical subjects

B Melloni

Publications and source records attributed to B Melloni.

42 records · Page 3Linked to original sources

[Pneumopathy caused by amiodarone. An often unrecognized iatrogenic entity].

Three cases of interstitial pneumopathy secondary to amiodarone are reported, in addition to almost 200 cases previously published in the literature. The main clinical, radiological, biological and evolutive characteristics are reminded in emphasizing the advantages of bronchioalveolar irrigation. Some factors seem to be predisposing, without any definite proof however. They are: high daily dosage, long term treatment, high cumulative dose, concomitant ingestion of another anti-arrhythmic medication, especially in elderly patients, and in patients who, before any treatment, presented a decreased total pulmonary capacity and a CO transfer capacity lower than 80 p. cent of the theoretical values. Discontinuation of amiodarone and administration of steroids usually produce a rapid regression of the clinical and radiological symptoms.

Aged↗

Is there a role of platelet-activating factor in human lung cancer?

Platelet-activating factor (PAF) is a lipid mediator that stimulates the in vitro growth of various human tumour cell lines and that enhances the effect of vascular endothelial growth factor that plays a key role during angiogenesis of human cancer. In this study, we assessed the levels of PAF and of the acetylhydrolase activity (AHA, the PAF degrading enzyme) in patients with lung cancer. Results indicated no significant differences between blood PAF amounts of lung cancer patients (91+/-33 pg/ml, n=31) and a control group of patients with chronic obstructive pulmonary disease (COPD) induced by habitual smoking (117+/-28 pg/ml, n=10). Similarly, their serum AHA levels were not different (67.9+/-3.0 nmol/min/ml as compared to 68.3+/-5.2 nmol/min/ml for lung cancer patients and controls, respectively). In contrast, PAF amounts were markedly (P=0.01, t-test for paired data) reduced in the lung tumour tissues (77+/-29 pg/g, n=10) as compared to the non-tumour tissues (208+/-67 pg/g, n=10). These low levels of PAF were not related to a lower amounts of the lyso-PAF precursor but to an elevated (P=0.01, t-test for paired data) AHA in the tumour tissues (37.0+/-4.9 nmol/min/g, n=10) as compared to the non-tumour tissues (24.6+/-2.6 nmol/min/ml, n=10). Reverse transcriptase polymerase chain reaction experiments showed the presence of the PAF receptor (PAF-R) transcript 1 but not transcript 2 in blood mononuclear cells of lung cancer patients and COPD patients. Flow cytometry experiments did not highlight differences in the number and the distribution of PAF-R on their circulating leukocytes. In conclusion, this clinical study highlights no evidence for a potential important role of PAF during human lung cancer.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Eyelid hyperlaxity and obstructive sleep apnea (O.S.A.) syndrome.

PURPOSE: An association between the floppy eyelid syndrome and the obstructive sleep apnea syndrome (O.S.A.) has been reported. We studied eyelid tissue elasticity and other ophthalmologic findings in a large number of patients with sleep disorders. MATERIAL AND METHODS: Sixty-nine patients with sleep disorders were evaluated. Two thirds were found to have O.S.A., and one third was treated at night by nasal continuous positive airway pressure (nasal C.P.A.P.). Slit lamp examination, eyelid measurements and Schirmer test were performed. RESULTS: Eyelid hyperlaxity was increased in patients with O.S.A. The floppy eyelid syndrome (associated papillary conjunctivitis), however, was rare. Associated corneal lesions were rare, and most patients were asymptomatic. In some cases, ocular irritation was due to air leaks from nasal C.P.A.P. A significant proportion of patients required treatment for primary open angle glaucoma. CONCLUSIONS: Our study of 69 patients found an association between O.S.A. and eyelid hyperlaxity.

Adult↗

Silica exposure induces cytotoxicity and proliferative activity of type II pneumocytes.

The contribution of the type II pneumocyte to the pathogenesis of silicosis is largely unknown. Prominent features of silicosis are hyperplasia and hypertrophy of type II epithelial cells, often accompanied by phospholipid accumulation in the lung. The biologic regulation of these events is poorly understood. This study addresses the question of a direct effect of silica on type II pneumocytes, since direct contact of the inhaled silica dust can occur in vivo. Type II cells were isolated from fetal rat lungs and their epithelial specificity was verified. Experiments were performed on 2nd passage monolayers in 2% serum. Repair, replication, and growth activity was evaluated by the incorporation of [3H]thymidine. Cytotoxicity was measured by quantitating the release of [14C]adenine and expressed as a cytotoxicity index (CI). Type II cell proliferation and cytotoxicity were evaluated for the mineral dusts silica (SiO2), aluminum-treated silica (SiO2AlK), and titanium (TiO2). Of these mineral dusts, only low concentrations of silica increased type II cell [3H]thymidine incorporation (silica 2.5 micrograms/mL: 52% above control, P less than .05; silica 20 micrograms/mL: 57% above control, P less than .02). In addition, silica increased the cell number significantly, although to a lesser degree. Exposure of the type II epithelial cells to silica dust for 24 h resulted in dose-dependent cytotoxicity (silica 10 micrograms/mL, CI = 9.1%, P less than .0002; 250 micrograms/mL, CI = 45.1%, P less than .0001). SiO2Al completely suppressed these proliferation and cytotoxicity effects, which were then similar to those of the inert dust, TiO2. These data suggest that direct exposure and contact of the type II pneumocytes to low-dose silica dust initiated repair, replication, and growth activity, while exposure to higher silica concentrations resulted in marked cytotoxicity. Both the repair, replication, and growth and the cytotoxic responses of the type II epithelial cells to silica exposure are related to the surface properties of silica.

Animals↗

Silica-exposed lung fluids have a proliferative activity for type II epithelial cells: a study on human and sheep alveolar fluids.

The type II pneumocyte changes in silicosis are characterized by hyperplasic and hypertrophic epithelial cells, and increased surfactant phospholipids in the bronchoalveolar lavage fluids (BALF). To assess the proliferative activity of alveolar lining fluids, BALF were applied on type II cell cultures. The growth-promoting activity was studied by tritiated thymidine incorporation for 24 h, and the cell number was measured by an electronic counting after a 48-h exposure time. Human BALF from 3 subsets of workers exposed to silica, staged according to ILO classification (silica exposed-workers without disease: hSWD n = 6; workers with simple silicosis: hSS n = 7; workers with confluent silicosis: hCS n = 5), were compared to healthy volunteers (hC n = 6). Sheep BALF from our model of silicosis and control animals (sS and sC) were studied at months 0, 6, and 24 of exposure. A clear enhancement was found in type II cell DNA synthesis under the effect of either normal and silicotic human or sheep BALF, in comparison to the negative control (p less than .05). In addition hSWD and hSS BALF as sS BALF at 20% dilution (peak activity) were significantly more stimulating than the normal alveolar fluids from the same species (p less than .05). The highest sheep BALF stimulatory activity was found at month 6 (170% of increase vs control, p less than .05) and clearly correlated with the high cellularity of BALF. The thymidine incorporation was supported by changes in cell counts. Sheep silicotic BALF run through G50 columns identified at least 3 molecular weight (MW) areas of mitogenic activity between 30 and 5 kDa. Biochemical characteristics of growth factors in the above MW range (PDGF, FGF, TGF alpha, EGF) were tested. Increased mitogenic activity of type II cells eluted from heparin sepharose columns loaded with silicotic sheep BALF, at 0.5 and 1 M NaCl, corresponded to the removal areas of PDGF- and acidic FGF-like heparin-binding molecules. The high proliferative activity on type II cells of the latter two molecules, alone or in combination with other growth factors, was demonstrated in vitro (greater than 9 x control). In conclusion, a stimulatory activity for type II cell growth was found in the normal human and sheep alveolar lining fluid. This activity was clearly enhanced in the early stages of human and sheep silicosis. The BALF type II cell growth factors had biochemical characteristics consistent with the PDGF- and FGF-like molecules.

Animals↗

Comparison between late onset and childhood asthma.

BACKGROUND: The onset of asthma frequently occurs after the age of 50 yr and the severity and causes of this late onset disease are poorly known. METHODS: 25 chronic asthmatics (65.7 +/- 6.5 yr) whose asthma started after the age of 50 yr were compared with 23 chronic asthmatic children (11.6 +/- 2.8 yr) and 24 COPD patients (61.6 +/- 3.4 yr). Both asthmatic groups had a similar apparent duration of asthma. None of the asthmatics was a smoker. All COPD were smokers. The severity of asthma was defined according to the Aas score. FVC, FEV1, MMEFR, Raw were tested and reversibility of bronchial obstruction was determined on Raw after salbutamol inhalation. Allergy was assessed by skin prick tests, RAST and total serum IgE (PRIST). RESULTS: Patients with childhood asthma had: 1) a significantly lower clinical severity of asthma; 2) a significantly less severe bronchial obstruction, and 3) a significantly greater reversibility than old age asthmatics. There was no significant difference between pulmonary function tests pre- and post-bronchodilators between COPD and old-age asthmatics. All asthmatic children and 40% of older patients were allergic. CONCLUSIONS: The occurrence of asthma in old age patients leads to a more severe course of the disease and allergy appears to play a role in many old age patients.

Adolescent↗