Role of size and composition of traffic and agricultural aerosols in the molecular responses triggered in airway epithelial cells

The increased levels of fine particles in the atmosphere are suspected of aggravating cardiopulmonary diseases, but the determinants of particle toxicity are poorly understood. This work aims at studying the role of composition and size in the toxicity of size-segregated particulate matter (PM) collected at different sites on human bronchial epithelial cells. PM were sampled at a traffic urban site (Urb S) and a rural site (Rur S) during the pesticide-spreading period. Ultrafine (UF), fine (F), and coarse (C) PM were characterized by their shape and chemical composition. Whatever the site, the finest PM (UF and F) induced the mRNA expression of CYP1A1, a biomarker of polyaromatic hydrocarbons (PAH) exposure, NQO-1 and heme HO-1, two antioxidant responsive element-driven genes; and two effect biomarkers, GM-CSF, a proinflammatory cytokine and amphiregulin (AR), a growth factor. C PM have a low or no effect. Interestingly, AR is more strongly induced by rural PM at the same mass exposure. These discrepancies suggest involvement of PM chemical composition: rural PM bearing the characteristics of aged aerosols with a high content of water-soluble components, and PM at urban kerbside sites containing mainly water-insoluble components. To conclude, we provide evidence that the finest PM fractions, whatever their origin, are more prone to induce exposure and effect biomarkers. The AR differential expression suggests a source-dependent effect requiring further investigation because of the role of this growth factor in airway remodeling, a characteristic feature of chronic lung respiratory diseases exacerbated by particulate pollution.     

Synthesis and cytotoxicity against tumor cells of pincer N-heterocyclic ligands and their transition metal complexes

The complexes: [CoL₂](ClO₄)₂ (1), [FeL₂](ClO₄)₂ (2), [NiL₂](ClO₄)₂ (3) and [MnLCl₂] (4), with L = diethyl-1,1′-(pyridine-2,6-diyl)bis(5-methyl-1H-pyrazole-3-carboxylate), were synthesized and fully characterized. Structural analysis revealed two distinct patterns influenced by the counter ions where L acts as a tridentate chelating ligand. The in vitro antitumor activity of L and L′ (diethyl 2,2′-(pyridine-2,6-diylbis(5-methyl-1H-pyrazole-3,1-diyl)) diacetate) as well as their metal complexes, was tested by the measurement of their cytostatic and cytotoxic properties towards the blood cancer mastocytoma cell line P815. We have also investigated their interactions with the antioxidant enzyme system. As a result, [MnL′Cl₂] (1′) exhibited the strongest activity compared to reference cis-platin with no cytotoxicity towards normal cells PBMCs (Peripheral Blood Mononuclear Cells). On the other hand, the antioxidant enzyme activity showed that the efficiency of metal complex 1′ against P815 tumor cells was via the rise in the SOD activity and inhibition of CAT enzyme activity. This proof of concept study allows disclosure of a new class of molecules in cancer therapeutics.

The complexes: [CoL₂](ClO₄)₂ (1), [FeL₂](ClO₄)₂ (2), [NiL₂](ClO₄)₂ (3) and [MnLCl₂] (4), with L = diethyl-1,1′-(pyridine-2,6-diyl)bis(5-methyl-1H-pyrazole-3-carboxylate), were synthesized and fully characterized.     

Bone Mineral Density of the Spine and Femur in Healthy Moroccan Women

Bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA) are widely used to diagnose osteoporosis and assess its severity. Previous studies show the necessity to establish reference data for bone mass measurements for each particular population. Such data are lacking for the Moroccan population. The aim of this study was to determine spine and femur BMD reference values for the Moroccan female population and to compare them with values from western and other Arab countries. A cross-sectional study of 569 Moroccan women, (randomly selected in the area of Rabat, the capital of Morocco, aged between 20 and 79 yr) was carried out to establish reference values of BMD. Measurements were taken at the lumbar spine and proximal femurs using DXA (Lunar Prodigy Vision, GE). The data were compared with published normative data taken by United States (U.S.), European, Kuwaiti, Lebanese, and Saudi women over 6 decades of age. The percentage of osteoporosis in postmenopausal women using our reference curve was compared to that observed when the other curves (US, European and Arab) implemented in the Lunar machine was used. Our results showed that the Moroccan women showed the expected decline in BMD at both sites with age after peaking at 20–29 years of age. Moroccan females have lower BMD at the spine than U.S., Europeans, and Kuwaitis (approximately 10–12% for patients older than 50 yr). The BMD values of the total femur in Moroccan females were close to western (European and American), and Kuwaitis, but higher than Lebanese and Saudis. Using our reference database, 37.9% of postmenopausal women had spine osteoporosis vs. 39.6% and 23.4% using US/European and Arabic Lunar reference values respectively. At the femurs, 6.7% had osteoporosis vs. 2.5% using the Arabic Lunar reference values. In conclusion, our study emphasizes the importance of using population-specific reference values for BMD measurements to avoid over or underdiagnosis of osteoporosis.     

Idiopathic chondrolysis of the hip

Idiopathic chondrolysis of the hip is a rare disease in which gradual necrosis of the hyaline cartilage covering the femoral head and acetabulum leads to joint space narrowing and motion restriction. Pain, motion range limitation, and radiographic joint space narrowing are the main manifestations. We report 2 cases in 15-year-old girls, one black and the other Caucasian. Unexplained pain and motion restriction in the left hip were the presenting manifestations. Narrowing of the hip joint space was noted on standard radiographs. Magnetic resonance imaging showed a joint effusion in 1 patient and unevenness of the femoral head contour in the other. Laboratory tests including microbiological studies were normal or negative. Nonspecific synovitis was found in biopsy specimens. Immobilization and traction were the main components of the treatment strategy.     

Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group

Background

There is currently no international consensus for first-line treatment (prior to autologous stem cell transplantation) in mantle cell lymphoma patients. Here, we investigated the efficacy and tolerance of VAD associated with chlorambucil (VAD+C) and rituximab or not before autologous stem cell transplantation.

Design and Methods

Between 1996 and 2005, 113 previously untreated mantle cell lymphoma patients were enrolled in two consecutive prospective phase II studies. Responses and response factors to the (R)VAD+C regimen were evaluated. The survival prognostic value of the MIPI score and Ki67 were also analyzed.

Results

The induction phase of 4 courses of (R)VAD+C showed very low hematologic and extra-hematologic toxicity (grade 3–4 thrombopenia and neutropenia, 9% and 2.7%, respectively and grade 3–4 extra-hematologic toxicities, 1.6%). Overall and complete response rates were 73% and 46%, respectively, and rose to 83% and 51% for the 70% of patients with less than two independent response factors (LDH, B symptoms and lymphocytosis). At the end of treatment, 65% of patients were in complete remission. Progression free and overall survival were significantly better in the transplanted population. The MIPI score was confirmed as a predictor of survival. Ki67, serum LDH, Performance Status (PS) and B symptoms were identified as independent prognostic factors of survival. A prognostic scoring system could stratify patients into three risk groups with markedly different median overall survival of 112, 44 and 11 months, respectively.

Conclusions

The (R)VAD+C is an effective regimen with very low toxicity. In addition to the MIPI score, Ki67 expression provides additional independent prognostic information for the prediction of overall survival (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00285389","term_id":"NCT00285389"}}NCT00285389).     

Prevalence and risk factors of osteoporosis in patients with Parkinson’s disease

Parkinson's disease (PD) is the most common cause of disability in the elderly. It is currently recognized as a cause of secondary osteoporosis. To evaluate the prevalence of osteoporosis in PD and detect its risk factors, 52 patients with PD (36 men/16 women) and 52 controls paired for age and sex were recruited. Clinical data including demography, disease duration and disease severity were collected. All subjects had bone mineral density (BMD) measured by dual energy X-ray absorptiometry, dorsal and lumbar spine X-ray, and biological exams (osteocalcin, CTX, parathormon). The mean age of the patients was 60.0 +/- 9.25 years [30-77], and the mean disease duration was 4.9 +/- 4.5 years [0.2-17]. Nine patients (17.3%) were osteoporotic and 28 (53.8%) osteopenic. BMD at the lumbar spine and the hip was lower among patients than controls (spine: 1.031 vs. 1.175 g/cm(2); P < 0.001; hip: 0.968 vs. 1.054; P = 0.02). PD patients with low BMD presented a more severe disease and an insufficient sun exposure and calcium intake. There was a positive statistically significant correlation between patients BMD and body mass index and negative correlation with age, severity of PD, and osteocalcin levels. The prevalence of osteoporosis/osteopenia is high in PD patients and seems related to the severity of the disease, an insufficient sun exposure and calcium intake. This osteoporosis constitutes with falls the major risk factors of fracture in PD patients.     

Reproducibility of bone mineral density measurements using dual X-ray absorptiometry in daily clinical practice

Bone mineral density (BMD) measurements are frequently performed repeatedly for each patient. Subsequent BMD measurements allow reproducibility to be assessed. Previous studies have suggested that reproducibility may be influenced by age and clinical status. The purpose of the study was to examine the reproducibility of BMD by dual energy X-ray absorptiometry (DXA) and to investigate the practical value of different measures of reproducibility in three distinct groups of subjects: healthy young volunteers, postmenopausal women and patients with chronic rheumatic diseases. Two hundred twenty-two subjects underwent two subsequent BMD measurements of the spine and hip. There were 60 young healthy subjects, 102 postmenopausal women and 60 patients with chronic rheumatic diseases (33 rheumatoid arthritis, 10 ankylosing spondylitis and 10 other systemic diseases). Forty-five patients (75%) among the third group were receiving corticosteroids. Reproducibility was expressed as the smallest detectable difference (SDD), coefficient of variation (CV), least significant change (LSC) and intraclass correlation coefficient (ICC). Sources of variation were investigated by linear regression analysis. The median interval between measurements was 0 days (range 0–7). The mean difference (SD) between the measurements (g/cm²) was –0.0001 (±0.003) and –0.0004 (±0.002) at L1-L4 and the total hip, respectively. At L1-L4 and the total hip, SDD (g/cm²) was ±0.04 and ±0.02, CV (%) was 2.02 and 1.29, and LSC (%) 5.60 and 3.56, respectively. The ICC at the spine and hip was 0.99 and 0.99, respectively. Only a minimal difference existed between the groups. Reproducibility in the three groups studied was good. In a repeated DXA scan, a BMD change, the least significant change (LSC) or the SDD should be regarded as significant. Use of the SDD is preferable to use of the CV and LSC because of its independence from BMD and its expression in absolute units. Expressed as SDD, a BMD change of at least ±0.04 g/cm² at L1-L4 and ±0.02 g/cm² at the total hip should be considered significant. This reproducibility seems independent from age and clinical status and improved in the hips by measuring the dual femur.     

Lumboscopic treatment of simple renal cysts

AIM: To assess feasibility and efficiency of lumboscopy in the treatment of simple renal cysts. METHODS: We report 12 cases of patients presenting symptomatic simple renal cysts treated by lumboscopy from January 2000 to December 2004. The mean age was 57 years (43-72). They were 11 women and one man. The main revealing sign was pain in each case. A mass was found in 2 cases (16 %). Ultrasonography was realized in all cases. Computed Tomography was realized in 4 cases (33 %). It was a unique cyst in 9 cases (75 %), a double cysts in 2 cases (17 %) and 4 cysts in 1 case (8 %). The mean size of the cysts was 7.7 cm (5-16). A parapyelic cyst was found in one case. All the patients were operated through a retroperitoneal approach. Excision of cyst dome was made. RESULTS: The mean operating time was 80 min (50-160). No intraoperative complication was noted. The mean hospital stay was 3 days (1-4). All the cysts were found to be benign histologically. No recurrence is noted with a mean follow-up of 21 months (5-31). CONCLUSION: Lumboscopy is a safe and effective technique in the treatment of the symptomatic simple renal cysts with a low rate of complications and recurrence.