A case-control study of lung cancer in Casablanca,Morocco

Objective: To evaluate etiologic risk factors for lung cancer in Casablanca, Morocco. Methods: We conducted a hospital-based case–control study that included 118 incident lung cancer cases and 235 age-, sex- and residence-matched controls. We analyzed the data using matched univariate and matched and unmatched multivariate logistic regression analyses. Results: Active tobacco smoking and history of chronic bronchitis were the strongest risk factors for lung cancer in the matched logistic regression model. Multivariate odds ratio (OR) and 95% confidence intervals varied from 1.79 (0.47–6.79) for former light smokers to 26.07 (6.58–103.27) for current heavy tobacco smokers at the time of disease occurrence. Combined use of hashish/kiff and snuff had an OR of 6.67 (1.65–26.90), whereas the OR for hashish/kiff (without snuff) was 1.93 (0.57–6.58). History of chronic bronchitis had an OR of 4.16 (1.76–9.85). Other slightly increased risks of lung cancer were found for exposure to passive smoking (1.36; 0.71–2.62), occupational exposures (1.75; 0.84–3.63), use of candles for lighting (1.44; 0.42–5.01), and poor ventilation of the kitchen (1.22; 0.57–2.58). Conclusions: This study confirms known risk factors for lung cancer and uncovers potential new etiologic ones such as the role of hashish/kiff.     

CT and MRI features of spinal hydatidosis. A report of 8 cases

PURPOSE: Hydatidosis affects the bone in 0.5 to 2% of cases, with 44% of these cases involving the spine. We report 8 cases of vertebral involvement evaluated by CT and/or MRI. Materials and Methods. This retrospective study from January 1996 to August 2000 included seven patients (5 men and 3 women) aged between 28 and 65 years old. The mean age was 45 years old. Five patients underwent CT scan (one by CT-myelography). MRI was available in 4 cases. RESULTS: Imaging showed multicystic bony lesions. Thoracic involvement was present in 4 cases, lumbar involvement in 2 cases, and sacral involvement in 2 cases. The process involved 2 adjacent vertebrae in 4 cases at the thoracic and lumbar levels and the entire sacrum in the other cases. Only one case of vertebral collapse was noted, but extension into the spinal canal was noted in all cases. Other sites of involvement were also noted, especially in adjacent soft tissues, liver and spleen. CONCLUSION: The presence of multicystic vertebral lesions with involvement of adjacent soft tissues and/or distant organs should raise the possibility of spinal hydatidosis in endemic countries.     

Preoperative Prediction of Small Bowel Length Using CT Scan and Tridimensional Reconstructions: a New Tool in Bariatric Surgery?

Purpose

During Roux-en-Y-gastric Bypass, the limb lengths are preoperatively determined regardless of individual small bowel length (SBL), which presents a great variability. Few studies highlighted anthropometric factors associated with SBL, and none attempted to predict SBL preoperatively.

Objective

The aim of this study is to evaluate factors correlated to SBL (anthropometric and radiologic) and to establish a preoperative SBL prediction.

Material and Methods

In this single-center prospective study, 30 adult patients who underwent laparotomy with a preoperative CT scan were included. Intraoperative SBL measurement was performed with an umbilical tape. Anthropometric parameters were age, gender, height, and BMI. 2D radiological measurements consisted of subcutaneous thickness, abdominal diameters, waist circumference, and mesenteric root length. 3D radiological volumetric reconstructions consisted of whole small bowel and mesentery (WSBM), lean small bowel and mesentery (LSBM), and fat small bowel and mesentery (FSBM).

Results

Mean intraoperative measurement of SBL was 531 ±?105 cm. Among the clinical and radiological measurements, the FSBM volume presented the greatest dispersion. Height (p?<?0.02) and LSBM volume (p?<?0.01) were significantly correlated to the SBL in univariate analysis. LSBM volume was the only measurement significantly associated with SBL in multivariate analysis (p?<?0.006). From the multivariate model, a formula was created to predict SBL. The mean percentage difference between predicted and intraoperative SBL measurements for all patients was 13.7%, and 8.4% for obese patients.

Conclusion

LSBM volume is significantly correlated to the SBL. A preoperative SBL prediction with low percentage error could be performed with LSBM volume.

     

Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesis

Neural stem cells (NSCs) are slowly dividing astrocytes that are intimately associated with capillary endothelial cells in the subventricular zone (SVZ) of the brain. Functionally, members of the vascular endothelial growth factor (VEGF) family can stimulate neurogenesis as well as angiogenesis, but it has been unclear whether they act directly via VEGF receptors (VEGFRs) expressed by neural cells, or indirectly via the release of growth factors from angiogenic capillaries. Here, we show that VEGFR-3, a receptor required for lymphangiogenesis, is expressed by NSCs and is directly required for neurogenesis. Vegfr3:YFP reporter mice show VEGFR-3 expression in multipotent NSCs, which are capable of self-renewal and are activated by the VEGFR-3 ligand VEGF-C in vitro. Overexpression of VEGF-C stimulates VEGFR-3-expressing NSCs and neurogenesis in the SVZ without affecting angiogenesis. Conversely, conditional deletion of Vegfr3 in neural cells, inducible deletion in subventricular astrocytes, and blocking of VEGFR-3 signaling with antibodies reduce SVZ neurogenesis. Therefore, VEGF-C/VEGFR-3 signaling acts directly on NSCs and regulates adult neurogenesis, opening potential approaches for treatment of neurodegenerative diseases.     

Arsthinol nanosuspensions: pharmacokinetics and anti‐leukaemic activity on NB4 promyelocytic leukaemia cells

Objectives The organoarsenical arsthinol was used in the 1950s in the treatment of amoebiasis and yaws and was considered as ‘highly tolerated’. The aim of this work was to study its anti‐leukaemic activity and to develop nanosuspensions of the drug, thereby limiting brain concentrations and the risk of encephalopathy. Methods Arsthinol nanosuspensions were produced by high‐pressure homogenization. The anti‐leukaemic activity was assessed on NB4 acute promyelocytic leukaemia cells (vs solutions of arsthinol, As₂O₃ and melarsoprol). In addition, a pharmacokinetics study was performed to compare the nanosuspensions and the solution of arsthinol. Key findings Arsthinol induced growth inhibition of NB4 cells at lower concentration (IC50 (concentration inhibiting growth by 50%) = 0.78 ± 0.08 μmol/l after 24 h) than As₂O₃ (IC50 = 1.60 ± 0.23 μmol/l after 24 h) or melarsoprol (IC50 = 1.44 ± 0.08 μmol/l after 24 h). When formulated as nanosuspension, arsthinol remained cytotoxic (IC50 = 1.33 ± 0.30 μmol/l after 24 h). This formulation also reduced the drug's access to the brain (C_max = 0.03 μmol/g) whereas bone marrow concentrations remained very high (C_max = 2 μmol/g). Conclusions Nanosuspensions of arsthinol could be proposed for further studies in the treatment of acute promyelocytic leukaemia.     

Push-and-pull regulation of the fusion pore by synaptotagmin-7

In chromaffin cells, Ca(2+) binding to synaptotagmin-1 and -7 triggers exocytosis by promoting fusion pore opening and fusion pore expansion. Synaptotagmins contain two C2 domains that both bind Ca(2+) and contribute to exocytosis; however, it remains unknown whether the C2 domains act similarly or differentially to promote opening and expansion of fusion pores. Here, we use patch amperometry measurements in WT and synaptotagmin-7-mutant chromaffin cells to analyze the role of Ca(2+) binding to the two synaptotagmin-7 C2 domains in exocytosis. We show that, surprisingly, Ca(2+) binding to the C2A domain suffices to trigger fusion pore opening but that the resulting fusion pores are unstable and collapse, causing a dramatic increase in kiss-and-run fusion events. Thus, synaptotagmin-7 controls fusion pore dynamics during exocytosis via a push-and-pull mechanism in which Ca(2+) binding to both C2 domains promotes fusion pore opening, but the C2B domain is selectively essential for continuous expansion of an otherwise unstable fusion pore.