Triptans reduce the inflammatory response in bacterial meningitis.

Severe headache and meningism provide clear evidence for the activation of trigeminal neurotransmission in meningitis. The authors assessed the antiinflammatory potential of 5HT1B/D/F receptor agonists (triptans), which inhibit the release of proinflammatory neuropeptides from perivascular nerve fibers. In a 6-hour rat model of pneumococcal meningitis, zolmitriptan and naratriptan reduced the influx of leukocytes into the cerebrospinal fluid, and attenuated the increase of regional cerebral blood flow. Elevated intracranial pressure as well as the brain water content at 6 hours was reduced by triptans. These effects were partially reversed by a specific 5HT1D as well as by a specific 5HT1B receptor antagonist. Meningitis caused a depletion of calcitonin gene-related peptide (CGRP) and substance P from meningeal nerve fibers, which was prevented by zolmitriptan and naratriptan. In line with these findings, patients with bacterial meningitis had significantly elevated CGRP levels in the cerebrospinal fluid. In a mouse model of pneumococcal meningitis, survival and clinical score at 24 hours were significantly improved by triptan treatment. The findings suggest that, besides mediating meningeal nociception, meningeal nerve fibers contribute to the inflammatory cascade in the early phase of bacterial meningitis. Adjunctive treatment with triptans may open a new therapeutic approach in the acute phase of bacterial meningitis.     

Statistical process control for hospitals: methodology, user education, and challenges

The health care industry is slowly embracing the use of statistical process control (SPC) to monitor and study causes of variation in health care processes. While the statistics and principles underlying the use of SPC are relatively straightforward, there is a need to be cognizant of the perils that await the user who is not well versed in the key concepts of SPC. This article introduces the theory behind SPC methodology, describes successful tactics for educating users, and discusses the challenges associated with encouraging adoption of SPC among health care professionals. To illustrate these benefits and challenges, this article references the National Hospital Quality Measures, presents critical elements of SPC curricula, and draws examples from hospitals that have successfully embedded SPC into their overall approach to performance assessment and improvement.     

The Antitumorigenic Function of EGFR in Metastatic Breast Cancer is Regulated by Expression of Mig6

Numerous studies by our lab and others demonstrate that epidermal growth factor receptor (EGFR) plays critical roles in primary breast cancer (BC) initiation, growth and dissemination. However, clinical trials targeting EGFR function in BC have lead to disappointing results. In the current study we sought to identify the mechanisms responsible for this disparity by investigating the function of EGFR across the continuum of the metastatic cascade. We previously established that overexpression of EGFR is sufficient for formation of in situ primary tumors by otherwise nontransformed murine mammary gland cells. Induction of epithelial-mesenchymal transition (EMT) is sufficient to drive the metastasis of these EGFR-transformed tumors. Examining growth factor receptor expression across this and other models revealed a potent downregulation of EGFR through metastatic progression. Consistent with diminution of EGFR following EMT and metastasis EGF stimulation changes from a proliferative to an apoptotic response in in situ versus metastatic tumor cells, respectively. Furthermore, overexpression of EGFR in metastatic MDA-MB-231 BC cells promoted their antitumorigenic response to EGF in three dimensional (3D) metastatic outgrowth assays. In line with the paradoxical function of EGFR through EMT and metastasis we demonstrate that the EGFR inhibitory molecule, Mitogen Induced Gene-6 (Mig6), is tumor suppressive in in situ tumor cells. However, Mig6 expression is absolutely required for prevention of apoptosis and ultimate metastasis of MDA-MB-231 cells. Further understanding of the paradoxical function of EGFR between primary and metastatic tumors will be essential for application of its targeted molecular therapies in BC.Abbreviations: Mig6, mitogen-induced gene-6; BC, breast cancer; EGFR, epidermal growth factor receptor; Mig6-EBR, EGFR binding region of Mig6; TGF-β, transforming growth factor-β; WT, wild type; NMuMG, normal murine mammary gland cells; NME, NMuMG cells transformed by EGFR overexpression; CCLE, Cell Line Encyclopedia; MET, mesenchymal-epithelial transition     

Treatment of acute pulmonary embolism: local effects of three hydrodynamic thrombectomy devices in an ex vivo porcine model.

PURPOSE: To report an ex vivo study on the local effects of hydrodynamic thrombectomy for the treatment of acute pulmonary embolism (off-label use). METHODS: Three devices (6-F AngioJet Xpeedior and 6-F and 8-F Oasis) were used for hydrodynamic thrombectomy inside the arteries of 24 inflated and perfused porcine lung explants. Each system was used at multiple positions inside 4 intact and 4 embolized lungs in vessels measuring 2 to 4 mm, 4 to 6 mm, 6 to 8 mm, and 8 to 10 mm. Angiograms prior to, during, and after catheter positioning and system operation were used to detect arterial wall trauma and to measure local clot removal per 30-second cycle. A total of 21 vessel wall samples were subjected to scanning electron microscopy (SEM) to evaluate non-perforating lesions. RESULTS: All systems were able to remove clot material. The average recanalized vessel length normalized to 30 seconds for vessel diameters of 2 to 4 and 8 to 10 mm, respectively, was 1.17 and 1.75 cm (AngioJet), 0.97 and 0.25 cm (6-F Oasis), and 2.2 and 1.05 cm (8-F Oasis). Perforations occurred during positioning of the 6-F Oasis (4/78 maneuvers) and 8-F Oasis (13/60), but not the AngioJet (0/89); perforations were also seen during system operation (AngioJet: 21/89 activations, 6-F Oasis: 4/78, and 8-F Oasis: 9/60; all lesions inside vessels <6 mm in diameter). SEM showed 35 lesions, 14 with perforation (contrast extravasation) and 21 without perforation (induced by the tip of the guidewire). CONCLUSION: The AngioJet was most efficient in clot removal, followed by the 8-F Oasis. The 6-F Oasis was least efficient, but had fewest complications. According to these experiments, the tested hydrodynamic thrombectomy devices may cause perforations in vessels <6 mm in diameter. Changes in catheter design to reduce system-specific complication rates or to improve the efficacy of clot removal are warranted.     

Closed-chest microdialysis to measure antibiotic penetration into human lung tissue.

The majority of bacterial lung infections are localized to the interstitial space fluid, which is therefore an important target site for antimicrobial chemotherapy. Direct measurement of interstitial concentrations of antimicrobial agents in human lung tissue would allow for a more informed approach to appropriate dosing of antimicrobial agents, but until now this was beyond technical reach. In this exploratory pharmacokinetic study, we measured the time versus concentration profile of cefpirome after a single intravenous dose administration of 2 g in the lung interstitial fluid by flexible microdialysis catheters, which were implanted during lung surgery for pulmonary tumors in five patients. Cefpirome concentrations in lung interstitial fluid were 66% of corresponding plasma values within the first 240 min, and exceeded minimal inhibitory concentrations of most relevant bacteria. The experimental procedure was well tolerated by the patients and no adverse events were observed. The present study provides evidence for the first time that closed chest microdialysis of the human lung is a feasible and safe method to measure lung concentrations in patients in vivo. The present data also corroborate the use of cefpirome as a valuable agent in the treatment of lung infections with most extracellular bacteria.     

Post-synthetically modified metal–porphyrin framework GaTCPP for carbon dioxide adsorption and energy storage in Li–S batteries

Lithium–sulphur batteries attract increasing interest due to their high theoretical specific capacity, advantageous economy, and “eco-friendliness”. In this study, a metal–organic framework (MOF) GaTCPP containing a porphyrinic base ligand was used as a conductive additive for sulphur. GaTCPP was synthesized, characterized, and post-synthetically modified by the transition metal ions (Co²⁺/Ni²⁺). The doping of GaTCPP ensured an increase in the carbon dioxide adsorption capacities, which were measured under different conditions. Post-synthetic modification of GaTCPP with Co²⁺/Ni²⁺ ions has been shown to increase carbon dioxide storage capacity from 22.8 wt% for unmodified material to 23.1 wt% and 26.5 wt% at 0 °C and 1 bar for Co²⁺ and Ni²⁺-doped analogues, respectively. As a conductive part of cathode material, MOFs displayed successful sulphur capture and encapsulation proven by stable charge/discharge cycle performances, high-capacity retention, and coulombic efficiency. The electrodes with pristine GaTCPP showed a discharge capacity of 699 mA h g⁻¹ at 0.2C in the fiftieth cycle. However, the doping of GaTCPP by Ni²⁺ has a positive impact on the electrochemical properties, the capacity increased to 778 mA h g⁻¹ in the fiftieth cycle at 0.2C.

Metal–porphyrin framework GaTCPP was used for carbon dioxide adsorption and as a host for preparation of a Li–S battery cathode material.     

Dermal psoriasis involving an oral split-skin graft. case report

Psoriasis is a chronic inflammatory skin disease which very rarely affects the oral cavity. It has many forms of expression on cutaneous and mucosal surfaces. This paper describes an unusual case of psoriasis with oral involvement affecting the skin graft used to reconstruct an oral mucosal defect. Diagnosis was based on clinical and microscopic findings and confirmed by the concurrent cutaneous disease.