Coagulopathy may be defined as the loss of balance between hemostatic and fibrinolytic processes resulting in excessive bleeding, intravascular thrombosis or abnormalities in coagulation testing. It is frequently encountered across a wide range of conditions seen in the neurocritical care unit and can contribute to poor outcomes. Early recognition and appropriate management are key, with traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage presenting unique challenges to the neurointensivist. We will discuss techniques to assess coagulopathies as well as treatment strategies for the brain injured patient.
Anticoagulants ; Blood Coagulation Disorders ; Brain ; Brain Injuries ; Cerebral Hemorrhage ; Hemorrhage ; Humans ; Platelet Aggregation Inhibitors ; Stroke ; Subarachnoid Hemorrhage ; Thrombosis

Inflammation is a common link in the pathophysiology of many neurological illnesses, including Alzheimer’s disease. Activated glial cells contribute to neuroinflammation by producing pro-inflammatory mediators. Naproxen and ibuprofen are nonsteroidal anti-inflammatory drugs with 2-aryl(s) propionic acid as a common pharmacophore. Here we designed a small series of naproxen and ibuprofen amide dimers and tested their effects on the expression of inducible nitric oxide synthase (iNOS), a neuroinflammatory enzyme in lipopolysaccharide (LPS)-stimulated BV2 mouse microglial cells. Of note, treatment with CNU 019, 020, 021, 023, 024, and 027 at 10 M markedly inhibited the LPS-induced iNOS expression in BV2 cells. CNU 024 was tested further at different concentrations to regulate the LPS-induced iNOS expression in BV2 cells. Treatment with CNU 024 at 5, 10, or 20 M dose-dependently suppressed the LPS-induced iNOS protein and mRNA expression levels in BV2 cells, in which maximal inhibition was seen at 20 M. CNU 024 treatment at doses tested further led to a concentration-dependent inhibition of the LPS-induced phosphorylation (activation) of p38 mitogen-activated protein kinase (MAPK) without influencing its total protein expression in BV2 cells, but it did not affect the LPS-induced activation of c-jun N-terminal kinase-1/2 and extracellular signal-regulated kinases-1/2 in these cells. In summary, our results demonstrate that CNU 024 inhibits the LPS-induced iNOS expression in BV2 cells, partly mediated by the inhibition of p38 MAPK. This work shows that CNU 024 could be a valuable ligand for further development as a potential drug candidate for treating neuroinflammatory pathologies.

INTRODUCTION: Stereotactic radiation therapy (SRT) can deliver highly focused radiation to a small and spherical target lesion with very high degree of mechanical accuracy. For non-spherical and large lesions, however, inclusion of the neighboring normal structures within the high dose radiation volume is inevitable in SRT. This is to report the beam shaping using the partial closure of the independent jaw in SRT and the verification of dose calculation and the dose display using a home-made soft ware. MATERIALS & METHODS: Authors adopted the idea to partially close one or more independent collimator jaw(s) in addition to the circular collimator cones to shield the neighboring normal structures while keeping the target lesion within the radiation beam field at all angles along the arc trajectory. The output factors (OF's) and the tissue-maximum ratios (TMR's) were measured using the micro ion chamber in the water phantom dosimetry system, and were compared with the theoretical calculations. A film dosimetry procedure was performed to obtain the depth dose profiles at 5 cm, and they were also compared with the theoretical calculations, where the radiation dose would depend on the actual area of irradiation. Authors incorporated this algorithm into the home-made SRT software for the isodose calculation and display, and was tried on an example case with single brain metastasis. The dose-volume histograms (DVH's) of the planning target volume (PTV) and the normal brain derived by the control plan were reciprocally compared with those derived by the plan using the same arc arrangement plus the independent collimator jaw closure. RESULTS: When using 5.0 cm diameter collimator, the measurements of the OF's and the TMR's with one independent jaw set at 30 mm (unblocked), 15.5 mm, 8.6 mm, and 0 mm from the central beam axis showed good correlation to the theoretical calculation within 0.5% and 0.3% error range. The dose profiles at 5 cm depth obtained by the film dosimetry also showed very good correlation to the theoretical calculations. The isodose profiles obtained on the home-made software demonstrated a slightly more conformal dose distribution around the target lesion by using the independent jaw closure, where the DVH's of the PTV were almost equivalent on the two plans, while the DVH's for the normal brain showed that less volume of the normal brain receiving high radiation dose by using this modification than the control plan employing the circular collimator cone only. CONCLUSION: With the beam shaping modification using the independent jaw closure, authors have realized wider clinical application of SRT with more conformal dose planning. Authors believe that SRT, with beam shaping ideas and efforts, should no longer be limited to the small spherical lesions, but be more widely applied to rather irregularly shaped tumors in the intracranial and the head and neck regions.
Axis, Cervical Vertebra ; Brain ; Film Dosimetry ; Head ; Jaw* ; Neck ; Neoplasm Metastasis ; Radiotherapy* ; Water

Conventional coronary angiography (CAG) has limitations in evaluating lesions producing ischemia. Three dimensional quantitative coronary angiography (3D-QCA) shows reconstructed images of CAG using computer based algorithm, the Cardio-op B system (Paieon Medical, Rosh Ha'ayin, Israel). The aim of this study was to evaluate whether 3D-QCA can reliably predict ischemia assessed by myocardial fractional flow reserve (FFR) < 0.80. 3D-QCA images were reconstructed from CAG which also were evaluated with FFR to assess ischemia. Minimal luminal diameter (MLD), percent diameter stenosis (%DS), minimal luminal area (MLA), and percent area stenosis (%AS) were obtained. The results of 3D-QCA and FFR were compared. A total of 266 patients was enrolled for the present study. FFR for all lesions ranged from 0.57 to 1.00 (0.85 +/- 0.09). Measurement of MLD, %DS, MLA, and %AS all were significantly correlated with FFR (r = 0.569, 0609, 0.569, 0.670, respectively, all P < 0.001). In lesions with MLA < 4.0 mm2, %AS of more than 65.5% had a 80% sensitivity and a 83% specificity to predict FFR < 0.80 (area under curve, AUC was 0.878). 3D-QCA can reliably predict coronary lesions producing ischemia and may be used to guide therapeutic approach for coronary artery disease.
Aged ; Coronary Angiography/*methods ; Coronary Circulation ; Coronary Stenosis/etiology/*physiopathology/*radiography ; Female ; *Fractional Flow Reserve, Myocardial ; Humans ; Imaging, Three-Dimensional/*methods ; Male ; Myocardial Ischemia/complications/physiopathology/*radiography ; Radiographic Image Enhancement/methods ; Radiographic Image Interpretation, Computer-Assisted/methods ; Reproducibility of Results ; Sensitivity and Specificity

PURPOSE: To improve the management of a medical linear accelerator, the records of operational failures of a Varian CL2100C over a ten year period were retrospectively analyzed. MATERIALS AND METHODS: The failures were classified according to the involved functional subunits, with each class rated into one of three levels depending on the operational conditions. The relationships between the failure rate and working ratio and between the failure rate and outside temperature were investigated. In addition, the average life time of the main part and the operating efficiency over the last 4 years were analyzed. RESULTS: Among the recorded failures (total 587 failures), the most frequent failure was observed in the parts related with the collimation system, including the monitor chamber, which accounted for 20% of all failures. With regard to the operational conditions, 2nd level of failures, which temporally interrupted treatments, were the most frequent. Third level of failures, which interrupted treatment for more than several hours, were mostly caused by the accelerating subunit. The number of failures was increased with number of treatments and operating time. The average life-times of the Klystron and Thyratron became shorter as the working ratio increased, and were 42 and 83% of the expected values, respectively. The operating efficiency was maintained at 95% or higher, but this value slightly decreased. There was no significant correlation between the number of failures and the outside temperature. CONCLUSION: The maintenance of detailed equipment problems and failures records over a long period of time can provide good knowledge of equipment function as well as the capability of predicting future failure. More rigorous equipment maintenance is required for old medical linear accelerators for the advanced avoidance of serious failure and to improve the quality of patient treatment.
Humans ; Particle Accelerators* ; Retrospective Studies

PURPOSE: To improve the management of a medical linear accelerator, the records of operational failures of a Varian CL2100C over a ten year period were retrospectively analyzed. MATERIALS AND METHODS: The failures were classified according to the involved functional subunits, with each class rated into one of three levels depending on the operational conditions. The relationships between the failure rate and working ratio and between the failure rate and outside temperature were investigated. In addition, the average life time of the main part and the operating efficiency over the last 4 years were analyzed. RESULTS: Among the recorded failures (total 587 failures), the most frequent failure was observed in the parts related with the collimation system, including the monitor chamber, which accounted for 20% of all failures. With regard to the operational conditions, 2nd level of failures, which temporally interrupted treatments, were the most frequent. Third level of failures, which interrupted treatment for more than several hours, were mostly caused by the accelerating subunit. The number of failures was increased with number of treatments and operating time. The average life-times of the Klystron and Thyratron became shorter as the working ratio increased, and were 42 and 83% of the expected values, respectively. The operating efficiency was maintained at 95% or higher, but this value slightly decreased. There was no significant correlation between the number of failures and the outside temperature. CONCLUSION: The maintenance of detailed equipment problems and failures records over a long period of time can provide good knowledge of equipment function as well as the capability of predicting future failure. More rigorous equipment maintenance is required for old medical linear accelerators for the advanced avoidance of serious failure and to improve the quality of patient treatment.
Humans ; Particle Accelerators* ; Retrospective Studies