Prediction of the Deposition of Dry Powder Aerosols

The trajectory, mass fluxes, and deposition of aerosolized particles in a complex tubular system have been predicted. A procedure based on Lagrangian stochastic modeling is proposed to enable the anticipation of such phenomena, taking advantage of experimental results to characterize the air flow. The predictions have been obtained for pharmaceutical aerosols delivered by dry powder inhalers. A critical assessment of the dispersion model has been carried out using data available in the literature. The procedure assumes a low volume fraction of particles in the simulation of turbulent dispersion, but deposition is physically based on the interaction between the particles and both solid and liquid surfaces. The results were confirmed by experimental tests of powder deposition, run according to the European Pharmacopoeia. A parametric study was also carried out with the aim of providing a more complete evaluation of the model’s performance. The comparison between predictions and experimental results has shown that the model properly describes the deposition of aerosolized particles.     

Risk factors for decreased total body and regional bone mineral density in hemodialysis patients with severe secondary hyperparathyroidism.

Hyperparathyroidism contributes significantly to decreased bone mineral density (BMD) in end-stage renal disease patients, but this negative influence is not homogeneous throughout the skeleton. We studied the BMD by dual-energy X-ray absorptiometry on total body and on different regions of the skeleton in 42 patients with severe hyperparathyroidism on hemodialysis. We also evaluated the relationship between different risk factors and BMD found on the regions examined in these patients. The legs and other sites where cortical bone predominate were mostly affected, whereas trabecular bone was relatively preserved. This is probably the result of the different effects of hyperparathyroidism on cortical and trabecular bone, but we cannot rule out the interference of ectopic calcifications and sclerotic lesions of vertebral end-plates falsely increasing lumbar spine BMD. The main determinants of low total-body BMD were, in order of importance, immobility, high intact parathyroid hormone levels, low body mass index, and low albumin. Eleven patients presented with pathologic fractures, mainly in the legs, and BMD was lower in this group than in patients without fractures. In conclusion, our study makes clear that hyperparathyroidism is a great threat to bone density in hemodialysis patients, mainly in the legs, the site mostly affected by fragility fractures in our patients. Physicians must worry not only with high parathyroid hormone levels, but also with the nutritional state of these patients.     

Comment on the 'pilot' GRACIA-2 randomized trial: reply

We thank Dr Villata et al. for their thought-provoking comments.Their concern about the suitableness to choose combined endpointsin clinical trials deserves some comment.     

Pseudotumor associated with polytetrafluoroethylene sleeves

We report the case of a patient who was operated on in February 2001. We performed a wedge resection of the upper right lobe. The pathologic examination demonstrated a lung adenocarcinoma (pT2N0M0, R0). We used staple line reinforcement material (ePTFE) during the operation because the patient had an important emphysema. We re-operated in January 2005 because during follow-up we observed a suspicious image that suggested a tumoral relapse. Histopathological study showed extrinsic material compatible with the one used in the original resection.     

El cultivo celular en la investigación básica del cáncer de mama

Resumen La técnica del cultivo celular es la que ha permitido conocer el comportamientoin vitro de las células cancerosas. En esta revisión pretendemos introducir las peculiaridades básicas del cultivo celular, referido especialmente a líneas cancerosas mamarias, relacionar el origen de las líneas celulares más utilizadas en la investigación de este cáncer, mencionar las técnicas de laboratorio que pueden aplicarse sobre estos cultivos y ejemplificar la utilidad de las mismas, tomando como modelo diversos trabajos que estudian los efectos del factor de crecimiento epidérmico sobre líneas celulares hormonoindependientes de cáncer de mama.      

Resolution of peripheral artery catheter-induced ischemic injury following prolonged treatment with topical nitroglycerin ointment in a newborn: a case report.

Tissue ischemia, necrosis, and gangrene are uncommon but well-described complications of arterial catheterization in the neonate. Treatment options for progressive tissue necrosis following arterial embolization and/or vasospasm are limited in these patients secondary to unpredictable pharmacokinetics and risks associated with systemic anticoagulation or vasodilatation in newborns. We report a case of a multidose regimen of topical 2% nitroglycerin ointment for reversing severe tissue ischemia following peripheral arterial line placement. The favorable response in this infant suggests that topical nitroglycerin therapy should be considered as potential therapy to ameliorate the effects of vascular compromise following arterial line placement in neonates.     

Ischemic stroke complicating cardiac catherization: case report.

Ischemic stroke occurs in 0.2-0.4% of patients undergoing left heart catheterization, and is responsible for 5-10% of the mortality associated with the procedure. The main predisposing factors for this complication are female gender, complex atherosclerotic plaques in the ascending aorta, and peripheral arterial disease. The possibility of timely intervention with reperfusion therapy supports close clinical monitoring during the immediate post-catheterization period. The cardiologist should be familiar with the various types of stroke reperfusion therapy and its indications according to the time interval between catheterization and the stroke. The decision should be discussed with neurology and neuroradiology.     

Benefits and risks of simvastatin in patients with familial hypercholesterolaemia.

Familial hypercholesterolaemia is a frequent, inherited, monogenic disorder, associated with accelerated development of atherosclerotic disease leading to coronary artery disease. Life expectancy of patients with familial hypercholesterolaemia is reduced by 15-30 years unless they are adequately treated with lipid-lowering therapy. Given the chronic nature of this disease, the selection of a therapeutic approach should be strongly based on its long-term safety and tolerability. The introduction of HMG-CoA reductase inhibitors has revolutionised the treatment of familial hypercholesterolaemia.Simvastatin 40-80 mg/day effectively reduces serum low density lipoprotein (LDL)-cholesterol levels. Furthermore, simvastatin reduces triglycerides and mildly raises high density lipoprotein-cholesterol levels. In addition to the hypolipidaemic effect, other potentially important effects, such as improvement of endothelial function and reduction of LDL oxidation and vascular inflammation, have been associated with HMG-CoA reductase inhibitor therapy. Simvastatin has also been shown to abolish the progression, and even facilitate the regression, of existing human atherosclerotic lesions.The good safety and tolerability profile of simvastatin is clearly highlighted by the low rate of therapy discontinuation observed in several population-based clinical trials. The most common adverse events leading to the discontinuation of therapy are gastrointestinal upset and headache. Asymptomatic elevations in liver transaminase levels and myopathy are uncommon.The overwhelming clinical evidence regarding the long-term use of HMG-CoA reductase inhibitor therapy in patients with familial hypercholesterolaemia together with the long-term safety data (particularly relating to simvastatin) provide support for the use of this drug as a first-line agent when pharmacological treatment is indicated. Early intervention with simvastatin treatment can be successfully implemented with favourable economic benefits.