Deposition of elafin in the involved vascular wall of neutrophil-mediated cutaneous vasculitis.

BACKGROUND: Neutrophil elastase plays an important role in skin inflammation induced by neutrophil infiltration. Elafin is an inducible elastase inhibitor expressed by keratinocytes, and is known to be involved in pathogenesis of neutrophilic skin disorders such as psoriasis. METHODS: Immunohistochemical studies of elafin expression in the cases of vasculitis were performed. Induction of elafin expression in cultured vascular cells and its effect on neutrophil migration were studied in vitro. RESULTS: A positive immunoreactivity was detected in polyarteritis nodosa, giant cell arteritis and Schönlein-Henoch purpura, but no immunoreactivity was found in Churg-Strauss syndrome. Elafin expression in cultured venous endothelial cells and arterial smooth muscle cells was undetectable, but induced by interleukin-1ß (IL-1ß) and IL-8. Elafin inhibited the elastin peptide-induced neutrophil chemotaxis at the concentration of 10(-8) -10(-5) mol/L. CONCLUSION: Elafin deposition induced by cytokines (IL-1ß or IL-8) will be an important regulator for the progress of leucocytoclastic vasculitis by functioning as an inhibitor for neutrophil chemotaxis as well as for vascular elastin degradation.

Coupled afterslip and transient mantle flow after the 2011 Tohoku earthquake.

Modeling of postseismic deformation following great earthquakes has revealed the viscous structure of the mantle and the frictional properties of the fault interface. However, for giant megathrust events, viscoelastic flow and afterslip mechanically interplay with each other during the postseismic period. We explore the role of afterslip and viscoelastic relaxation and their interaction in the aftermath of the 2011 M w (moment magnitude) 9.0 Tohoku earthquake based on a detailed model analysis of the postseismic deformation with laterally varying, experimentally constrained, rock rheology. Mechanical coupling between viscoelastic relaxation and afterslip notably modifies both the afterslip distribution and surface deformation. Thus, we highlight the importance of addressing mechanical coupling for long-term studies of postseismic relaxation, especially in the context of the geodynamics of the Japan trench across the seismic cycle.

Direct electrical bipolar electrostimulation for functional cortical and subcortical cerebral mapping in awake craniotomy. Practical considerations.

INTRODUCTION: The aim of brain glioma surgery is to maximize the quality of resection, while minimizing the risk of sequelae. Due to the frequent location of gliomas near or within eloquent areas, owing to their infiltrative feature, and because of major interindividual variability, the anatomofunctional organization and connectivity must be studied individually. Therefore, to optimize the benefit-to-risk ratio of surgery, intraoperative functional mapping is extensively used. MATERIAL AND METHODS: This article aims at describing the rationale, indications and practical aspects of intraoperative direct electrical bipolar electrostimulation for cortical and subcortical mapping under awake conditions using the asleep-awake asleep anaesthetic protocol in the setting of cerebral gliomas. We will address the operative approach, including patient positioning, functional mapping resection strategy, anaesthetic conditions, as well as tips and pitfalls. RESULTS: The intraoperative direct electrical bipolar electrostimulation enables: (i) to study the real-time individual cortical functional organization; (ii) to study the anatomofunctional subcortical connectivity along the resection; (iii) to tailor the resection according to individual corticosubcortical functional boundaries. This is an easy, accurate, reliable, well-tolerated and safe detection technique of both cortical and subcortical functionally essential structures during resection. It should be performed in the context of a standardized protocol involving members of both anaesthesiology and neurosurgery teams at neurosurgical centers specialized in surgical neuro-oncology. CONCLUSION: Intraoperative direct electrical bipolar electrostimulation for cortical and subcortical mapping under awake conditions is currently considered the "gold standard" clinical tool for brain mapping during cerebral resection in neuro-oncology.

A first look at duloxetine (Cymbalta) in a postmortem laboratory.

Duloxetine (Cymbalta) is manufactured by Eli Lilly and Company and is the newest antidepressant to be approved by the Food and Drug Administration (FDA). Duloxetine is a potent serotonin and norepinephrine reuptake inhibitor that is also used for the management of pain associated with diabetic peripheral neuropathy. With the introduction of any new drug, toxicology laboratories around the nation experience the same problems: lack of information about the chemical and physical properties of the new drug, detection methodologies from biological specimens, and interpretation of quantitative values. Since its FDA approval in 2002, the Los Angeles County Department of Coroner Toxicology Laboratory has detected and quantitated duloxetine in 12 postmortem cases. The isolation of duloxetine from postmortem specimens consisted of a basic, liquid-liquid (n-butylchloride) extraction procedure. Duloxetine was detected in our general, pharmaceutical, basic drugs screen that utilizes gas chromatography-nitrogen-phosphorus detection (GC-NPD) and GC-mass spectrometry (MS), and the quantitation was specifically by GC-MS. Linearity was achieved from 0.05 to 3.0 mg/L with the limit of detection at 0.03 mg/L. Presented are the case histories, demographics, cause/manner of death, and the postmortem tissue distribution ranges of duloxetine: central blood, not detected (ND)-0.59 mg/L (12 cases); femoral blood, ND-0.26 mg/L (9 cases); vitreous humor, ND-0.23 mg/L (4 cases); liver, 0.28-22 mg/kg (8 cases); gastric contents, 0.08-86 mg total (6 cases); bile, 0.57-3.1 mg/L (7 cases); and urine, 0.07-0.47 mg/L (6 cases). The detection and quantitation of duloxetine in these 12 case studies are considered the first to be reported in the literature; all are designed to aid the forensic toxicologist with the interpretation of his/her own casework.

Technical nuances of commonly used vascularised flaps for skull base reconstruction.

BACKGROUND AND METHODS: Reconstruction with a vascularised flap provides the most reliable outcome, with post-operative cerebrospinal fluid leak rates of less than 5 per cent. This article aims to review and summarise the critical technical aspects of the vascularised flaps most commonly used for skull base reconstruction. RESULTS: Vascularised flaps are classified as intranasal or extranasal. The intranasal group includes the Hadad-Bassagaisteguy nasoseptal flap, the Caicedo reverse nasoseptal flap, the nasoseptal rescue flap, the posteriorly or anteriorly based lateral wall flaps, and the middle turbinate flap. Extranasal flaps include the transfrontal pericranial and transpterygoid temporoparietal flaps. CONCLUSION: The Hadad-Bassagaisteguy nasoseptal flap is overwhelmingly favoured for reconstructing extensive defects of anterior, middle and posterior cranial base. Its pertinent technical features are described. However, it is essential to master the skills required for the various extranasal or regional vascularised flaps because each can offer a reconstructive alternative for specific patients, especially when open approaches are needed and/or intranasal vascularised flaps are not feasible.

Drugs of abuse found in fatally injured drivers in Los Angeles County.

Blood or urine specimens from nearly 600 fatally injured drivers in two Los Angeles County studies were analyzed for the presence of alcohol and other drugs of abuse, including PCP, cocaine, opiates and marijuana. The results of the preliminary study indicate that 65 out of 102 fatally injured drivers had used alcohol and/or another drug of abuse - 34 had used alcohol only, 12 had used one or more other drug(s) of abuse, and 19 had used alcohol in combination with another drug of abuse. The results of the larger follow-up study, begun a year later, indicate a continued high level of both alcohol use (41.5%) and marijuana use (19%) with moderate cocaine usage (8%) and low levels (less than 2%) of barbiturate and PCP usage.

Duragesic transdermal patch: postmortem tissue distribution of fentanyl in 25 cases.

Fentanyl is a potent, short-acting narcotic analgesic widely used as a surgical anesthetic and for the control of pain when administered in the form of a transdermal patch. The success of the patch can be attributed to fentanyl's low molecular weight and its highly lipophilic nature, which enables it to be readily absorbed through the skin and subsequently distributed throughout the body. Over the past three years, the Los Angeles County Coroner's Toxicology Laboratory has encountered 25 cases involving Duragesic patches (fentanyl), and their postmortem tissue distributions are presented here. The analysis of fentanyl from postmortem specimens (3-mL or g sample size) consisted of an n-butyl chloride basic extraction followed by identification and quantitation on a gas chromatograph-mass spectrometer using the selected ion monitoring (SIM) mode. The fentanyl ions monitored were m/z 245, 146, and 189 and the internal standard, fentanyl-d5 ions, were m/z 250, 151, and 194 (quantitation ion underlined). The linear range of the assay was 1.67 microg/L to 500 microg/L with the limit of quantitation and detection of 1.67 microg/L. The postmortem tissue distribution ranges of fentanyl in the 25 fatalities were as follows: heart blood, 1.8-139 microg/L (23 cases); femoral blood, 3.1-43 microg/L (13 cases); vitreous, +<2.0-20 microg/L (4 cases); liver, 5.8-613 microg/kg (22 cases); bile, 3.5-262 microg/L (15 cases); urine, 2.9-895 microg/L (19 cases); gastric, 0-1200 microg total (17 cases); spleen, 7.8-79 microg/kg (3 cases); kidney, 11 microg/kg (1 case); and lung, 31 microg/kg (1 case). The age of the decedents in this study ranged from 19 to 84, with an average age of 46. The modes of death included 15 accidental, 5 natural, 3 suicidal, and 2 undetermined. The main objectives of this paper are to show the prevalence of fentanyl patches in our community and to aid the forensic toxicologist with the interpretation of postmortem fentanyl levels in casework.

Whole blood deproteinization for drug screening using automatic pipettors.

Automating the initial screening of postmortem blood and other tissues for drugs of abuse requires a pipetting procedure that is compatible with immunoassay screening tests. The deproteinization procedure uses a zinc sulfate-5-sulfosalicylic acid reagent to precipitate blood proteins. This procedure for deproteinization of whole blood and tissue homogenates is compatible with coated tube radioimmunoassays (RIA) and can therefore be used in automating the initial screening step.

Distribution of mirtazapine (Remeron) in thirteen postmortem cases.

Mirtazapine is a new antidepressant agent that entered the United States market in April 1996. To date, the literature provides limited information about therapeutic blood concentrations and virtually no information about postmortem levels. The Los Angeles County Coroner's Toxicology Laboratory has encountered 13 cases where postmortem tissue distributions of mirtazapine were determined. The analysis of mirtazapine from postmortem specimens (2-mL sample size) consisted of an n-butylchloride basic extraction procedure with identification and quantitation on a gas chromatograph-nitrogen-phosphorus detector. Linearity was achieved from 0.025 mg/L to 3.0 mg/L with a limit of quantitation of 0.025 mg/L. Confirmation of mirtazapine was performed on a gas chromatograph-mass spectrometer by comparison with a pure analytical standard. The tissue distribution of mirtazapine are in the following concentration ranges: heart blood 0.03-0.57 mg/L (13 cases), femoral blood 0.04-0.24 mg/L (9 cases), vitreous 0.06-0.10 mg/L (3 cases), liver 0.32-2.1 mg/kg (12 cases), bile 0.40-6.6 mg/L (7 cases), urine 0.12-2.5 mg/L (11 cases), kidney 0.23 mg/kg (1 case), spleen 0.17 mg/kg (1 case), and gastric 0.001-2.7 mg total (9 cases). Mirtazapine was not implicated in the cause of death in any of the 13 cases studied. These cases are being presented to aid the forensic toxicologist in the evaluation of postmortem mirtazapine levels.

Findings in newborns of cocaine-abusing mothers.

Cocaine has recently been shown to affect the outcome of pregnancy when taken by pregnant women. The authors measured fetal concentrations of cocaine and benzoylecgonine and reviewed autopsy and historical data for 62 successive infants who died at less than two days of age and were seen at the Los Angeles County Office of the Chief Medical Examiner-Coroner. Of 43 infants without an obvious cause of death at autopsy, cocaine or benzoylecgonine or both were present in 40%. None of the parameters studied predicted which infants would show cocaine or benzoylecgonine. We conclude that cocaine and benzoylecgonine concentrations should be measured on all infants who die at less than two days of age when the cause of death is not evident at gross autopsy.

Dermoid cyst of the auricle: report of two cases.

Dermoid cyst of the auricle is a very rare lesion in Japan. The cysts studied for this report demonstrated a benign clinical course with a tendency to become larger. The clinical and pathological characteristics of these cysts are reviewed.

[EEG analysis of high-dose fentanyl anesthesia--a comparison of rapid sequence anesthesia and the conventional method].

Twenty-one patients who underwent cardiac surgery were assigned to receive high-dose fentanyl rapid sequence anesthesia or conventional high-dose fentanyl anesthesia. In conventional method group, power of delta wave decreased with respect to time. But in rapid sequence group, no decrease was seen until the end of operation. Good maintenance of delta wave in rapid sequence group may be achieved by higher plasma fentanyl concentration and the absence of acute tolerance. In conclusion, high-dose fentanyl rapid sequence anesthesia is a useful method for cardiac surgery.

[The importance of pain control with morphine for terminally ill patient care for at home].

From April 1987 to June 1994, 81 patients of terminally ill had been care at home. In these home care, 38 patients received pain control with morphine. In 29 patients, pain control had been started before home care but in 9 patients pain control had been started under home care. Routes of morphine administration were oral in 24 cases and rectal in 14 cases. In cases of oral routes, finally 2 cases converted to rectal routes and 2 cases converted to subcutaneous routes. Duration of treatment were from 2 days to 741 days (average 72 days). Dosage of morphine were 7.5 mg to 480 mg (average 116 mg). Two patients lived but 24 patients died at home and 12 patients died at hospital. We concluded that palliative care especially pain control with morphine was very important care for patients of terminally ill who wanted care at home and ultimately die at home. We had to make ourself master of method pain control with morphine.

[Silicon of the medium in the postoperative maxillary cyst].

As part of a study on chronic inflammatory disease of the mucous membrane, silicon of the medium in postoperative maxillary cysts and in other cysts was measured, and following results were obtained. Silicon concentrations of the medium in the postoperative maxillary cysts and in the postoperative ethmoidal cysts were 34.5 ppm and 42.9 ppm (geometrical mean) respectively, and they were higher than in other primary cysts such as frontal cyst, nasal vestibular cyst, and dental cyst. The silicon content of the medium in the postoperative maxillary cyst varied with the water content of the medium; the lower the water content the higher was the silicon content and the relationship was expressed by the following equation. log S = 7.43 + 7.14 log d-6.14 log w, where S = Si (mcg), d = dry weight (g.) and w = wet weight (g.). The high concentration of silicon in the postoperative cyst was considered to be due to the large amount of silicon transudate from the surrounding fibrous tissue through a highly damaged or missing epithelial wall of the cyst.