Biological markers as indicators of exposure and pneumoconiotic risk: Prospective study

This research is designed to evaluate a number of biological markers to estimate harmful exposure on coal miners from different mining regions in France and to relate the outcome to differences in prevalence of coal worker pneumoconiosis (CWP) between these regions. Eight epidemiological groups of active and ex-miners (smokers and non-smokers) have been selected in the French collieries (North, Lorraine and Provence) according to their occupational and pneumoconiotic status. The following biomarkers have been evaluated: cellularity of sputum, elementary analysis of particles in TEM/EDAX, plasma neutral metalloendo peptidase elastase type (NMEP), leucocyte elastase (HLE), fibronectin (FN) and elastin peptides. Pulmonary alveolitis, expressed by sputum cellularity, is different between active workers groups but not related to the general background of pneumoconiosis prevalence in the French collieries. In the plasma parameters, fibronectin, HLE and NMEP significantly increased in all groups of coal mine workers as compared to the control group, except for fibronectin parameter in Lorraine collierie. The degree of increase of these parameters allow us to discriminate the different groups and suggest that plasma FN, HLE and NMEP may be considered as biological markers of chronic inhalation of coal mine dust particles. The decrease of elastin peptides level in the Lorraine group alone suggests a specific alteration of elastin metabolism. These parameters were not related to the development of pneumoconiosis and its degree of severity.     

Myofibroblasts and the progression of diabetic nephropathy

Background. The cellular mediators of progressive renal fibrosis in diabetic nephropathy remain unknown. Myofibroblasts have been implicated in the pathogenesis of experimental and clinical renal fibrosis. Their role in the progression of diabetic nephropathy is the subject of this study.Subjects and methods. We have studied by immunohistochemistry the expression of cytoskeletal proteins associated with the activation of myofibroblasts; &agr;-smooth-muscle actin (&agr;-SMA), vimentin (Vi) and desmin (D), in the kidneys of 25 patients with diabetic nephropathy (5 patients with diabetic nephropathy (5 patients had a superimposed glomerulonephritis). Comparisons were made with normal tissue for three kidneys removed for renal-cell carcinoma. Correlations were studied between clinical and biochemical parameters with the expression renal cytoskeletal proteins. Results. In normal kidneys, cells expressing &agr;-SMA were confined to the vascular media and adventia while immunoreactive Vi was detected in glomerular epithelial cells. In diabetic kidneys, cells expressing &agr;-SMA were detected primarily in the renal interstitium and to a lesser extent in some glomeruli in association with mesangial proliferation. Vimentin immunostain decreased in glomeruli displaying diabetic hyalinosis and sclerosis. By contrast, strong Vi immunoreactivity was noted in atrophic diabetic tubules and to a lesser extent in the interstitium. Desmin was not detected in either normal or diabetic kidneys. Close correlations were observed between the expression of renal cytoskeletal proteins and the progression of renal insufficiency. Interstitial &agr;-SMA proved to be a predictor of progressive diabetic nephropathy (R² for 1/serum Cr slope=0.608, P=0.00001). This predictive parameters; tubular atrophy (R²=0.477, P=0.00004) and interstitial fibrosis (R²=0.28, P=0.001). Conclusion. We have demonstrated in this study the neoexpression of cytoskeletal proteins within diabetic kidneys. This has allowed the identification of new predicting histological markers for the progression of diabetic nephropathy.     

Prostaglandin synthesis by squamous carcinoma cells of head and neck, and its inhibition by non-steroidal anti-inflammatory drugs

The purpose of this study was to determine the nature and amounts of prostaglandins (PGs) produced by squamous carcinoma cells (SCC) and the sensitivity of these cells to non-steroidal anti-inflammatory drugs. SCC of four lines of the tongue and one line of facial epidermis of humans were incubated in phosphate buffer solution with ¹⁴C-arachidonic acid (AA). Radioactive metabolites in aqueous methanol were chromatographed on Sep-Pack CIS cartridges, separated and quantitated by means of TLC, autoradiography, and liquid scintillation counting. The results showed that cyclooxygenase products, PGs, were the major products formed by all cell lines, and PGE₂ was predominant among the PGs detected. Two radioactive bands corresponding to PGF_2α and three unseparated standards of PGA₂, 15-keto-PGE₂, and 13,14-dihydro-15-keto-PGE₂were detected in lesser amounts. Very small amounts of the lipoxygenase products 12-and 15-HETE were found. The concentrations of indomethacin, ibuprofen and aspirin required to inhibit 50% of PGE₂ synthesis (IC₅₀) by SCC lines were .008- .080, .080–6.4 and 32–88 μM, respectively.     

Non-Hodgkin's lymphoma with protein S deficiency]

Venous thrombosis is rare in children. It can be either acquired or of constitutional origin. Thrombosis during non-Hodgkin lymphoma remains exceptional and is usually locally associated to the tumoral process, raising the issue of its tumoral or cruoric nature. The treatment is based on anticoagulation concomitantly to chemotherapy. We report on a 4-year-old boy admitted for mediastinal non-Hodgkin lymphoma, who developed a thrombosis of the superior vena cava associated to protein S-deficiency. The mechanism of thrombosis may have been multifactorial: associated protein S-deficiency, vascular compression, tumoral process and chemotherapy.     

Recombinant activated factor VII for intractable bleeding post splenectomy in a patient with myeloproliferative disorder.

Recombinant activated factor VII has been Food and Drug Administration approved to treat hemorrhages in hemophiliac patients with inhibitors and in acquired hemophilia patients. Recombinant activated factor VII use has also been considered for the management of uncontrolled bleeding in a number of congenital and acquired hemostatic abnormalities. The myeloproliferative disorders are a group of clonal hematologic diseases where, frequently, abnormal platelet function is considered a hallmark. This is the first case report addressing the clinical benefit of off-label use of recombinant activated factor VII in an attempt to control intractable bleeding in a patient with a myeloproliferative disorder after splenectomy.