Intravenous self-administration of metallic mercury in attempted suicide. Report of a case with serial roentgenographic and physiologic studies over an 18-month period

This report describes a 23-year-old white man who injected metallic mercury from a thermometer into his antecubital vein in an attempt at suicide. Despite the persistence of mercury throughout both pulmonary fields on chest x-ray films over an 18-month period of observation, no clinical or physiologic derangement of pulmonary function has developed. In addition, no clinical or biochemical evidence of acute or chronic mercury poisoning in any other organ has appeared during these 18 months, even though metallic mercury is seen in the abdominal viscera on roentgenographic examination. The literature on suicidal and accidental poisoning with metallic mercury is reviewed.     

PET and SPECT in the management of lung cancer

Lung cancer is the leading cause of cancer deaths in men and women. Most recently in 2001, the Health Care Financing Administration has expanded Medicare coverage for positron emission tomography (PET) to include the diagnosis, staging, and restaging of lung cancer. This review discusses the current metabolic imaging techniques, including the role of PET, single-photon emission computed tomography (SPECT), and the new hybrid PET in the diagnosis, staging, and treatment of lung cancer. The technological advantages, disadvantages, and benefits are compared. PET has the highest detection efficiency than gamma camera based devices. PET when merged with computed tomography (CT) forms the powerful hybrid PET-CT system, capable both of metabolic and anatomic imaging. Clinical imaging pathways based on these newer modalities for the management of lung cancer are proposed. Technological advances in metabolic imaging linked with therapy driven protocols and outcomes may further provide cutting edge modalities that positively impact on dismal lung cancer mortality statistics.     

Positive airway pressure in patients receiving intermittent mandatory ventilation at zero rate. The role in weaning in chronic obstructive pulmonary disease

Over a 20-month period, we treated 180 mechanically ventilated patients in our respiratory intensive care unit. Among these patients, we observed an interesting previously unreported phenomenon in 20 patients with severe chronic obstructive disease. During the weaning from mechanical ventilators of these 20 patients, there was a marked clinical deterioration when the mode of ventilation was changed from intermittent mandatory ventilation (IMV) at zero rate to that of a T-tube setup. To explain this previously unreported observation, we studied and compared nine different intubated patients for possible differences in airway pressure between IMV set up at zero rate and a T tube. We observed that peak airway pressures were greater on IMV at zero rate compared to the peak airway pressures on the T piece in all nine patients. At the end of expiration, seven out of the nine patients had higher airway pressures on IMV at zero rate compared to the T tube. These differences in the peak airway pressures and end-expiratory pressures were statistically significant in both groups. In spite of the obvious limitation of extrapolating the experimental results obtained in one group of patients to explain the clinical observations made in another group of patients, we believe that the higher airway pressures on the IMV system (even without any mechanical ventilation) prevent early collapse of the airways, and this may be of significant importance in successfully weaning patients with COPD.     

Efficacy of gemcitabine conjugated and miRNA-205 complexed micelles for treatment of advanced pancreatic cancer

Clinical effectiveness of gemcitabine in pancreatic cancer is hindered due to its rapid plasma metabolism and development of chemo-resistance. We have previously delineated the significant role of miRNAs in mediating the growth and proliferation of cancer stem cells (CSCs) which in turn result in chemo-resistance, invasion and metastasis. Here, we designed self-assembling, gemcitabine conjugated cationic copolymers for co-delivery of a tumor suppressor miRNA-205 (miR-205) and evaluated their in vivo efficacy in a pancreatic cancer ectopic tumor model developed using gemcitabine resistant MIA PaCa-2^R cells. Combination formulations showed mean a particle size of <100 nm and gemcitabine payload of >10% w/w, exhibited miRNA complexation at N/P ratio of 4/1, sustained release of gemcitabine for >10 days, transfection efficiency of >90%, extended miRNA and drug stability in serum. Functional assays in gemcitabine resistant MIA PaCa-2^R and CAPAN-1^R pancreatic cancer cells revealed that the combination formulations effectively reversed chemo-resistance, invasion and migration. In pancreatic tumor model, the combination formulation treated group showed significant inhibition of tumor growth. Immuno-hiostochemical analysis revealed decreased tumor cell proliferation with increased apoptosis in the animals treated with miR-205 and gemcitabine combination.     

Self-assembling lisofylline-fatty acid conjugate for effective treatment of diabetes mellitus

Lisofylline is an anti-inflammatory agent with proven anti-diabetic activity. Its high solubility and rapid metabolism results in poor bioavailability and short half-life, limiting its clinical utility. We have synthesized Lisofylline-Linoleic acid (LSF-LA) conjugate which self-assembled into micelles (156.9 nm; PDI 0.187; CMC 1 μg/mL; aggregation number 54) without any surfactant and showed enhanced cellular uptake. It protected MIN6 insulinoma cells from cytokine induced cell death and enhanced insulin production under inflammatory conditions. It also suppressed the proliferation of activated peripheral blood mononuclear cells and reduced the production of inflammatory cytokines, IFN-γ and TNF-α. LSF-LA micelles exhibited reduced protein binding, significantly higher half-life (5.7-fold) and higher apparent volume of distribution (5.3-fold) than free LSF. In T1D animals, reduced blood glucose levels were observed at a reduced dose (~15 mg/kg, once daily of LSF-LA micelles vs. 25 mg/kg, twice daily of free LSF) that was further confirmed by immunohistochemical analysis.