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Sample records for post-mortem clinical pharmacology

  1. Dutch guideline for clinical foetal-neonatal and paediatric post-mortem radiology, including a review of literature.

    Science.gov (United States)

    Sonnemans, L J P; Vester, M E M; Kolsteren, E E M; Erwich, J J H M; Nikkels, P G J; Kint, P A M; van Rijn, R R; Klein, W M

    2018-06-01

    Clinical post-mortem radiology is a relatively new field of expertise and not common practice in most hospitals yet. With the declining numbers of autopsies and increasing demand for quality control of clinical care, post-mortem radiology can offer a solution, or at least be complementary. A working group consisting of radiologists, pathologists and other clinical medical specialists reviewed and evaluated the literature on the diagnostic value of post-mortem conventional radiography (CR), ultrasonography, computed tomography (PMCT), magnetic resonance imaging (PMMRI), and minimally invasive autopsy (MIA). Evidence tables were built and subsequently a Dutch national evidence-based guideline for post-mortem radiology was developed. We present this evaluation of the radiological modalities in a clinical post-mortem setting, including MIA, as well as the recently published Dutch guidelines for post-mortem radiology in foetuses, neonates, and children. In general, for post-mortem radiology modalities, PMMRI is the modality of choice in foetuses, neonates, and infants, whereas PMCT is advised in older children. There is a limited role for post-mortem CR and ultrasonography. In most cases, conventional autopsy will remain the diagnostic method of choice. Based on a literature review and clinical expertise, an evidence-based guideline was developed for post-mortem radiology of foetal, neonatal, and paediatric patients. What is Known: • Post-mortem investigations serve as a quality check for the provided health care and are important for reliable epidemiological registration. • Post-mortem radiology, sometimes combined with minimally invasive techniques, is considered as an adjunct or alternative to autopsy. What is New: • We present the Dutch guidelines for post-mortem radiology in foetuses, neonates and children. • Autopsy remains the reference standard, however minimal invasive autopsy with a skeletal survey, post-mortem computed tomography, or post-mortem

  2. [Post-mortem microbiology analysis].

    Science.gov (United States)

    Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

    2013-12-01

    Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population. Crown Copyright © 2012. Published by Elsevier Espana. All rights reserved.

  3. Prevalence and concordance between the clinical and the post-mortem diagnosis of dementia in a psychogeriatric clinic.

    Science.gov (United States)

    Grandal Leiros, B; Pérez Méndez, L I; Zelaya Huerta, M V; Moreno Eguinoa, L; García-Bragado, F; Tuñón Álvarez, T; Roldán Larreta, J J

    The aim of our study is to describe the types of dementia found in a series of patients and to estimate the level of agreement between the clinical diagnosis and post-mortem diagnosis. We conducted a descriptive analysis of the prevalence of the types of dementia found in our series and we established the level of concordance between the clinical and the post-mortem diagnoses. The diagnosis was made based on current diagnostic criteria. 114 cases were included. The most common clinical diagnoses both at a clinical and autopsy level were Alzheimer disease and mixed dementia but the prevalence was quite different. While at a clinical level, prevalence was 39% for Alzheimer disease and 18% for mixed dementia, in the autopsy level, prevalence was 22% and 34%, respectively. The agreement between the clinical and the autopsy diagnoses was 62% (95% CI 53-72%). Almost a third of our patients were not correctly diagnosed in vivo. The most common mistake was the underdiagnosis of cerebrovascular pathology. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Clinical and post mortem analysis of combat neck injury used to inform a novel coverage of armour tool.

    Science.gov (United States)

    Breeze, J; Fryer, R; Hare, J; Delaney, R; Hunt, N C; Lewis, E A; Clasper, J C

    2015-04-01

    There is a requirement in the Ministry of Defence for an objective method of comparing the area of coverage of different body armour designs for future applications. Existing comparisons derived from surface wound mapping are limited in that they can only demonstrate the skin entry wound location. The Coverage of Armour Tool (COAT) is a novel three-dimensional model capable of comparing the coverage provided by body armour designs, but limited information exists as to which anatomical structures require inclusion. The aim of this study was to assess the utility of COAT, in the assessment of neck protection, using clinically relevant injury data. Hospital notes and post mortem records of all UK soldiers injured by an explosive fragment to the neck between 01 Jan 2006 and 31 December 2012 from Iraq and Afghanistan were analysed to determine which anatomical structures were responsible for death or functional disability at one year post injury. Using COAT a comparison of three ballistic neck collar designs was undertaken with reference to the percentage of these anatomical structures left exposed. 13/81 (16%) survivors demonstrated complications at one year, most commonly upper limb weakness from brachial plexus injury or a weak voice from laryngeal trauma. In 14/94 (15%) soldiers the neck wound was believed to have been the sole cause of death, primarily from carotid artery damage, spinal cord transection or rupture of the larynx. COAT objectively demonstrated that despite the larger OSPREY collar having almost double the surface area than the two-piece prototype collar, the percentage area of vulnerable cervical structures left exposed only reduced from 16.3% to 14.4%. COAT demonstrated its ability to objectively quantify the potential effectiveness of different body armour designs in providing coverage of vulnerable anatomical structures from different shot line orientations. To improve its utility, it is recommended that COAT be further developed to enable weapon

  5. An evaluation of the DRI-ETG EIA method for the determination of ethyl glucuronide concentrations in clinical and post-mortem urine.

    Science.gov (United States)

    Turfus, Sophie C; Vo, Tu; Niehaus, Nadia; Gerostamoulos, Dimitri; Beyer, Jochen

    2013-06-01

    A commercial enzyme immunoassay for the qualitative and semi-quantitative measurement of ethyl glucuronide (EtG) in urine was evaluated. Post-mortem (n=800), and clinical urine (n=200) samples were assayed using a Hitachi 902 analyzer. The determined concentrations were compared with those obtained using a previously published liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of EtG and ethyl sulfate. Using a cut-off of 0.5 µg/ml and LC-MS/MS limit of reporting of 0.1 µg/ml, there was a sensitivity of 60.8% and a specificity of 100% for clinical samples. For post-mortem samples, sensitivity and specificity were 82.4% and 97.1%, respectively. When reducing the cut-off to 0.1 µg/ml, the sensitivity and specificity were 83.3% and 100% for clinical samples whereas for post-mortem samples the sensitivity and specificity were 90.3 % and 88.3 %, respectively. The best trade-offs between sensitivity and specificity for LC-MS/MS limits of reporting of 0.5 and 0.1 µg/ml were achieved when using immunoassay cut-offs of 0.3 and 0.092 µg/ml, respectively. There was good correlation between quantitative results obtained by both methods but analysis of samples by LC-MS/MS gave higher concentrations than by enzyme immunoassay (EIA), with a statistically significant proportional bias (P<0.0001, Deming regression) for both sample types. The immunoassay is reliable for the qualitative and semi-quantitative presumptive detection of ethyl glucuronide in urine. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Post-mortem MRI as an alternative to non-forensic autopsy in foetuses and children: from research into clinical practice

    Science.gov (United States)

    Addison, S; Arthurs, O J

    2014-01-01

    Although post-mortem MRI (PMMR) was proposed as an alternative to conventional autopsy more than a decade ago, the lack of systematic validation has limited its clinical uptake. Minimally invasive autopsy (MIA) using PMMR together with ancillary investigations has now been shown to be as accurate as conventional autopsy in foetuses, newborns and infants and is particularly useful for cerebral, cardiac and genitourinary imaging. Unlike conventional autopsy, PMMR provides a permanent three-dimensional auditable record, with accurate estimation of internal organ volumes. MIA is becoming highly acceptable to parents and professionals, and there is widespread political support and public interest in its clinical implementation in the UK. In the short to medium term, it is desirable that a supraregional network of specialist centres should be established to provide this service within the current National Health Service framework. PMID:24288400

  7. Post-mortem CT evaluation of atlanto-occipital dissociation.

    Science.gov (United States)

    Madadin, Mohammed; Samaranayake, Ravindra Priyalal; O'Donnell, Chris; Cordner, Stephen

    2017-02-01

    Atlanto-occipital dissociation injury is an important injury in forensic pathology practice. Radiological diagnosis of atlanto-occipital dissociation clinically is assessed by direct measurement of occipito-vertebral skeletal relationships. Different measurements may be used to diagnose atlanto-occipital dissociation, including the basion-dens interval (BDI) and basion-axial interval (BAI). It is not known whether the normal ante-mortem measurements of BDI and BAI described in the literature are applicable to post-mortem CT images of the occipito-cervical junction (OCJ) or whether these measurements could be affected by early post-mortem changes. This study aims to compare post-mortem BDI and BAI measurements with ante-mortem values. Post-mortem CT scans of the cervical spines of 100 deceased adults were reviewed, and the BDI and BAI were measured. Different parameters were recorded in each case. The results from this study suggest that there are no effects of post-mortem changes on the measurement of BAI as relied upon clinically. There appear to be some effects of fully established rigor mortis on BDI measurement, shortening it. This may have consequences for the post mortem diagnosis of atlanto-occipital dissociation. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  8. Quality of coroner's post-mortems in a UK hospital.

    Science.gov (United States)

    Al Mahdy, Husayn

    2014-01-01

    The aim of this paper was, principally, to look at the coroner's post-mortem report quality regarding adult medical patients admitted to an English hospital; and to compare results with Royal College of Pathologists guidelines. Hospital clinical notes of adult medical patients dying in 2011 and who were referred to the coroner's office to determine the cause of death were scrutinised. Their clinical care was also reviewed. There needs to be a comprehensive approach to coroner's post-mortems such as routinely taking histological and microbiological specimens. Acute adult medical patient care needs to improve. Steps should be taken to ensure that comprehensive coroner's post-mortems are performed throughout the UK, including with routine histological and microbiological specimens examination. Additionally, closer collaboration between clinicians and pathologists needs to occur to improve emergency adult medical patient clinical care. The study highlights inadequacies in coroner's pathology services.

  9. Differences in sampling techniques on total post-mortem tryptase.

    Science.gov (United States)

    Tse, R; Garland, J; Kesha, K; Elstub, H; Cala, A D; Ahn, Y; Stables, S; Palmiere, C

    2017-11-20

    The measurement of mast cell tryptase is commonly used to support the diagnosis of anaphylaxis. In the post-mortem setting, the literature recommends sampling from peripheral blood sources (femoral blood) but does not specify the exact sampling technique. Sampling techniques vary between pathologists, and it is unclear whether different sampling techniques have any impact on post-mortem tryptase levels. The aim of this study is to compare the difference in femoral total post-mortem tryptase levels between two sampling techniques. A 6-month retrospective study comparing femoral total post-mortem tryptase levels between (1) aspirating femoral vessels with a needle and syringe prior to evisceration and (2) femoral vein cut down during evisceration. Twenty cases were identified, with three cases excluded from analysis. There was a statistically significant difference (paired t test, p sampling methods. The clinical significance of this finding and what factors may contribute to it are unclear. When requesting post-mortem tryptase, the pathologist should consider documenting the exact blood collection site and method used for collection. In addition, blood samples acquired by different techniques should not be mixed together and should be analyzed separately if possible.

  10. Post-mortem radiology-a new sub-speciality?

    International Nuclear Information System (INIS)

    O'Donnell, C.; Woodford, N.

    2008-01-01

    Computed tomography (CT) and magnetic resonance imaging (MRI) examinations of deceased individuals are increasingly being utilized in the field of forensic pathology. However, there are differences in the interpretation of post-mortem and clinical imaging. Radiologists with only occasional experience in post-mortem imaging are at risk of misinterpreting the findings if they rely solely on clinical experience. Radiological specialists working in a co-operative environment with pathologists are pivotal in the understanding of post-mortem CT and MRI, and its appropriate integration into the autopsy. This has spawned a novel subspecialty called post-mortem radiology or necro-radiology (radiology of the deceased). In the future it is likely that whole-body CT will be incorporated into the routine forensic autopsy due its ability to accurately detect and localise abnormalities commonly seen in forensic practice, such as haematoma, abnormal gas collections, fractures, and metallic foreign bodies. In the next 5-10 years most forensic institutes will seek regular access to such CT facilities or install machines into their own mortuaries. MRI is technically more problematic in the deceased but the improved tissue contrast over CT means that it is also very useful for investigation of pathology in the cranial, thoracic, and abdominal cavities, as well as the detection of haematoma in soft tissue. In order for radiologists to be an integral part of this important development in forensic investigation, radiological organizations must recognize the subspecialty of post-mortem radiology and provide a forum for radiologists to advance scientific knowledge in the field

  11. Relationship between clinical and postmortem evaluation in repeat breeder beef cows Relação entre características clínicas e post-mortem em vacas de corte repetidoras de serviço

    Directory of Open Access Journals (Sweden)

    Rogério Ferreira

    2008-08-01

    Full Text Available The objective of this study was to investigate the causes of the repeat breeder syndrome comparing clinical signs and postmortem findings in beef cows. The identification of factors affecting the reproductive tract can support decisions as to whether treatment of repeat breeder cows is justifiable than culling. Since all animals were submitted to clinical examination before being slaughtered, this study has a differential approach when compared with others, where genital tracts from abattoir were examined. In this study, 130 crossbred cows and heifers that have failed to conceive after three or more services were identified, submitted to a clinical examination and blood collection for karyotyping and sent to an abattoir. postmortem examinations included macroscopic evaluation of the genital tracts, bacteriology and histopathology of the uterus. Uterine alterations were predominant followed by oviduct and ovarian pathologies. Histopathological examination was more sensitive as a diagnostic tool than clinical examination. Repeat breeder cows had a predominance of uterine abnormalities (95%, such as inflammatory (42.9% and degenerative (59.7% conditions. Oviduct abnormalities were found in 29.8 % of animals. Furthermore, 1 out 10 karyotyped cows showed aneuploidy. Thus, this study stressed the importance of laboratory exams in the diagnosis of the causes of infertility of repeat breeder cows.O objetivo deste estudo foi avaliar as causas de infertilidade em vacas de corte repetidoras de serviço, relacionando sinais clínicos com características laboratoriais post-mortem. A identificação dos fatores que afetam o desempenho reprodutivo pode fornecer uma fundamentação científica para auxiliar na decisão quanto ao destino de vacas repetidoras de serviço; tratamento ou descarte. Este estudo tem abordagem diferencial dos trabalhos que contemplam somente a ocorrência de alterações post-mortem do trato genital. A correlação das altera

  12. Application of contrast media in post-mortem imaging (CT and MRI).

    Science.gov (United States)

    Grabherr, Silke; Grimm, Jochen; Baumann, Pia; Mangin, Patrice

    2015-09-01

    The application of contrast media in post-mortem radiology differs from clinical approaches in living patients. Post-mortem changes in the vascular system and the absence of blood flow lead to specific problems that have to be considered for the performance of post-mortem angiography. In addition, interpreting the images is challenging due to technique-related and post-mortem artefacts that have to be known and that are specific for each applied technique. Although the idea of injecting contrast media is old, classic methods are not simply transferable to modern radiological techniques in forensic medicine, as they are mostly dedicated to single-organ studies or applicable only shortly after death. With the introduction of modern imaging techniques, such as post-mortem computed tomography (PMCT) and post-mortem magnetic resonance (PMMR), to forensic death investigations, intensive research started to explore their advantages and limitations compared to conventional autopsy. PMCT has already become a routine investigation in several centres, and different techniques have been developed to better visualise the vascular system and organ parenchyma in PMCT. In contrast, the use of PMMR is still limited due to practical issues, and research is now starting in the field of PMMR angiography. This article gives an overview of the problems in post-mortem contrast media application, the various classic and modern techniques, and the issues to consider by using different media.

  13. Post-mortem CT-coronary angiography

    DEFF Research Database (Denmark)

    Pøhlsgaard, Camilla; Leth, Peter Mygind

    2007-01-01

    post-mortem coronary angiography and computerized tomography.  We describe how to prepare and inject the contrast medium, and how to establish a CT-protocol that optimizes spatial resolution, low contrast resolution and noise level. Testing of the method on 6 hearts, showed that the lumen...

  14. Reviviendo la consulta post-mortem.

    OpenAIRE

    Armando Cortés

    2009-01-01

    Por estos días se inaugura el “Centro de consulta post-mortem del Hospital Universitario del Valle”, una denominación más apropiada para la autopsia «ver por sí mismo» o cualquiera de sus sinónimos necropsia, examen post-mortem, necroscopia, o tanatopsia; todos ellos no aceptados y condicionados por factores culturales, sociales o religiosos. Estos términos han alcanzado una connotación claramente negativa en el ambiente médico y en el público general. Quizás, el mejor término sea «consulta p...

  15. Post mortem examination report concerning Nadim Nuwwara

    DEFF Research Database (Denmark)

    Leth, Peter Mygind

    2014-01-01

    Post mortem examination report concerning Nadim Nuwawara, 17-years old, who was killed may 15 2014 in Beitunia near Rahmallah, Palestine. The examination was performed by an international team consisting of dr. Saber Al-Aloul, director of the Medico Legal Institute at Quds University, dr. Marc A....... Krouse, Deputy Chief Medical Examiner, Office of Chief Medical Examiner, Fort Worth, Texas, USA, dr. Chen Kugel, Chief Forensic Pathologist, Abu Kabir Institute of Forensic Medicine, Tel Aviv, dr. Ricardo Pablo Nachman, forensic expert at Abu Kabir Institute of Forensic Medicine, Tel Aviv and dr. Peter...

  16. Isolation of primary microglia from the human post-mortem brain: effects of ante- and post-mortem variables.

    Science.gov (United States)

    Mizee, Mark R; Miedema, Suzanne S M; van der Poel, Marlijn; Adelia; Schuurman, Karianne G; van Strien, Miriam E; Melief, Jeroen; Smolders, Joost; Hendrickx, Debbie A; Heutinck, Kirstin M; Hamann, Jörg; Huitinga, Inge

    2017-02-17

    Microglia are key players in the central nervous system in health and disease. Much pioneering research on microglia function has been carried out in vivo with the use of genetic animal models. However, to fully understand the role of microglia in neurological and psychiatric disorders, it is crucial to study primary human microglia from brain donors. We have developed a rapid procedure for the isolation of pure human microglia from autopsy tissue using density gradient centrifugation followed by CD11b-specific cell selection. The protocol can be completed in 4 h, with an average yield of 450,000 and 145,000 viable cells per gram of white and grey matter tissue respectively. This method allows for the immediate phenotyping of microglia in relation to brain donor clinical variables, and shows the microglia population to be distinguishable from autologous choroid plexus macrophages. This protocol has been applied to samples from over 100 brain donors from the Netherlands Brain Bank, providing a robust dataset to analyze the effects of age, post-mortem delay, brain acidity, and neurological diagnosis on microglia yield and phenotype. Our data show that cerebrospinal fluid pH is positively correlated to microglial cell yield, but donor age and post-mortem delay do not negatively affect viable microglia yield. Analysis of CD45 and CD11b expression showed that changes in microglia phenotype can be attributed to a neurological diagnosis, and are not influenced by variation in ante- and post-mortem parameters. Cryogenic storage of primary microglia was shown to be possible, albeit with variable levels of recovery and effects on phenotype and RNA quality. Microglial gene expression substantially changed due to culture, including the loss of the microglia-specific markers, showing the importance of immediate microglia phenotyping. We conclude that primary microglia can be isolated effectively and rapidly from human post-mortem brain tissue, allowing for the study of the

  17. Delayed Post Mortem Predation in Lightning Strike Carcasses ...

    African Journals Online (AJOL)

    Campbell Murn

    An adult giraffe was struck dead by lightning on a game farm outside. Phalaborwa, South Africa in March 2014. Interestingly, delayed post-mortem predation occurred on the carcass, which according to the farm owners was an atypical phenomenon for the region. Delayed post-mortem scavenging on lightning strike ...

  18. Effects of post mortem temperature on rigor tension, shortening and ...

    African Journals Online (AJOL)

    Fully developed rigor mortis in muscle is characterised by maximum loss of extensibility. The course of post mortem changes in ostrich muscle was studied by following isometric tension, shortening and change in pH during the first 24 h post mortem within muscle strips from the muscularis gastrocnemius, pars interna at ...

  19. Blast furnace hearth lining: post mortem analysis

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Bruno Vidal de; Vernilli Junior, Fernando, E-mail: bva@usp.br [Universidade de Sao Paulo (USP), Lorena, SP (Brazil). Escola de Engenharia; Neves; Elton Silva; Silva, Sidiney Nascimento [Companhia Siderugica Nacional (CSN), Rio de Janeiro, RJ (Brazil)

    2017-05-15

    The main refractory lining of blast furnace hearth is composed by carbon blocks that operates in continuous contact with hot gases, liquid slag and hot metal, in temperatures above 1550 deg C for 24 hours a day. To fully understand the wear mechanism that acts in this refractory layer system it was performed a Post Mortem study during the last partial repair of this furnace. The samples were collected from different parts of the hearth lining and characterized using the following techniques: Bulk Density and Apparent Porosity, X-Ray Fluorescence, X-ray Diffraction, Scanning Electron Microscopy with Energy-dispersive X-Ray Spectroscopy. The results showed that the carbon blocks located at the opposite side of the blast furnace tap hole kept its main physicochemical characteristics preserved even after the production of 20x10{sup 6} ton of hot metal. However, the carbon blocks around the Tap Hole showed infiltration by hot metal and slag and it presents a severe deposition of zinc and sulfur over its carbon flakes. The presence of these elements is undesired because it reduces the physic-chemical stability of this refractory system. This deposition found in the carbon refractory is associated with impurities present in the both coke and the sinter feed used in this blast furnace in the last few years. (author)

  20. Blast furnace hearth lining: post mortem analysis

    International Nuclear Information System (INIS)

    Almeida, Bruno Vidal de; Vernilli Junior, Fernando

    2017-01-01

    The main refractory lining of blast furnace hearth is composed by carbon blocks that operates in continuous contact with hot gases, liquid slag and hot metal, in temperatures above 1550 deg C for 24 hours a day. To fully understand the wear mechanism that acts in this refractory layer system it was performed a Post Mortem study during the last partial repair of this furnace. The samples were collected from different parts of the hearth lining and characterized using the following techniques: Bulk Density and Apparent Porosity, X-Ray Fluorescence, X-ray Diffraction, Scanning Electron Microscopy with Energy-dispersive X-Ray Spectroscopy. The results showed that the carbon blocks located at the opposite side of the blast furnace tap hole kept its main physicochemical characteristics preserved even after the production of 20x10"6 ton of hot metal. However, the carbon blocks around the Tap Hole showed infiltration by hot metal and slag and it presents a severe deposition of zinc and sulfur over its carbon flakes. The presence of these elements is undesired because it reduces the physic-chemical stability of this refractory system. This deposition found in the carbon refractory is associated with impurities present in the both coke and the sinter feed used in this blast furnace in the last few years. (author)

  1. Histopathological features of post-mortem pituitaries: A retrospective analysis

    Directory of Open Access Journals (Sweden)

    Francisco José Tortosa Vallecillos

    Full Text Available SUMMARY Objective: As a result of the use of neuroimaging techniques, silent pituitary lesions are diagnosed more and more frequently; however, there are few published post-mortem studies about this gland. Incidence data of pituitary lesions are rare and in Portugal they are outdated or even non-existent. The aim of this study is to determine the prevalence of normal patterns and incidental post-mortem pituitary pathology at Centro Hospitalar Lisboa Norte, analyzing the associations with clinical data and assessing the clinical relevance of the findings. Method: We reviewed retrospectively and histologically 167 pituitaries of a consecutive series of autopsies from the Department of Pathology of this centre. They were done between 2012 and 2014, and in all cases medical records were reviewed. The morphological patterns observed, were classified into three major groups: 1 Normal histological patterns and variants; 2 Infectious-inflammatory pathology, metabolic and vascular disorders; 3 Incidental primary proliferation and secondary to systemic diseases. Results: The subjects included in this study were of all age groups (from 1 day to 91 years old, 71 were female and 96 male. Fifty-seven of these glands didn’t show any alteration; 51 showed colloid cysts arising from Rathke cleft; 44 presented hyperplasia in adenohypophysis and we identified 20 adenomas in 19 glands (immunohistochemically, eight PRL-producing and five ACTH-producing tumors, ten of which associated with obesity, 11 to hypertension and six to diabetes mellitus. There were two cases with metastasis. Conclusion: Subclinical pathology in our country is similar to that seen in other parts of the world, but at older ages.

  2. [Legal aspects of post-mortem radiology in the Netherlands].

    Science.gov (United States)

    Venderink, W; Dute, J C J

    2016-01-01

    In the Netherlands, the application of post-mortem radiology (virtual autopsy) is on the rise. Contrary to conventional autopsy, with post-mortem radiology the body remains intact. There is uncertainty concerning the legal admissibility of post-mortem radiology, since the Dutch Corpse Disposal Act does not contain any specific regulations for this technique. Autopsy and post-mortem radiology differ significantly from a technical aspect, but these differences do not have far-reaching legal consequences from a legal perspective. Even though the body remains intact during post-mortem radiology, the bodily integrity of a deceased person is breached if it would be applied without previously obtained consent. This permission can only be obtained after the relatives are fully informed about the proposed activity. In this respect, it is not relevant which technique is used, be it post-mortem radiology or autopsy. Therefore, the other legal conditions for post-mortem radiology are essentially identical to those for autopsy.

  3. Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome

    NARCIS (Netherlands)

    Lahrouchi, Najim; Raju, Hariharan; Lodder, Elisabeth M.; Papatheodorou, Efstathios; Ware, James S.; Papadakis, Michael; Tadros, Rafik; Cole, Della; Skinner, Jonathan R.; Crawford, Jackie; Love, Donald R.; Pua, Chee J.; Soh, Bee Y.; Bhalshankar, Jaydutt D.; Govind, Risha; Tfelt-Hansen, Jacob; Winkel, Bo G.; van der Werf, Christian; Wijeyeratne, Yanushi D.; Mellor, Greg; Till, Jan; Cohen, Marta C.; Tome-Esteban, Maria; Sharma, Sanjay; Wilde, Arthur A. M.; Cook, Stuart A.; Bezzina, Connie R.; Sheppard, Mary N.; Behr, Elijah R.

    2017-01-01

    Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and

  4. Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome

    DEFF Research Database (Denmark)

    Lahrouchi, Najim; Raju, Hariharan; Lodder, Elisabeth M

    2017-01-01

    BACKGROUND: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. OBJECTIVES: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy...

  5. 42 CFR 35.16 - Autopsies and other post-mortem operations.

    Science.gov (United States)

    2010-10-01

    ... AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem... to in writing by a person authorized under the law of the State in which the station or hospital is... made a part of the clinical record. [25 FR 6331, July 6, 1960] ...

  6. Quantification of maceration changes using post mortem MRI in fetuses

    International Nuclear Information System (INIS)

    Montaldo, P.; Addison, S.; Oliveira, V.; Lally, P. J.; Taylor, A. M.; Sebire, N. J.; Thayyil, S.; Arthurs, O. J.

    2016-01-01

    Post mortem imaging is playing an increasingly important role in perinatal autopsy, and correct interpretation of imaging changes is paramount. This is particularly important following intra-uterine fetal death, where there may be fetal maceration. The aim of this study was to investigate whether any changes seen on a whole body fetal post mortem magnetic resonance imaging (PMMR) correspond to maceration at conventional autopsy. We performed pre-autopsy PMMR in 75 fetuses using a 1.5 Tesla Siemens Avanto MR scanner (Erlangen, Germany). PMMR images were reported blinded to the clinical history and autopsy data using a numerical severity scale (0 = no maceration changes to 2 = severe maceration changes) for 6 different visceral organs (total 12). The degree of maceration at autopsy was categorized according to severity on a numerical scale (1 = no maceration to 4 = severe maceration). We also generated quantitative maps to measure the liver and lung T 2 . The mean PMMR maceration score correlated well with the autopsy maceration score (R 2 = 0.93). A PMMR score of ≥4.5 had a sensitivity of 91 %, specificity of 64 %, for detecting moderate or severe maceration at autopsy. Liver and lung T 2 were increased in fetuses with maceration scores of 3–4 in comparison to those with 1–2 (liver p = 0.03, lung p = 0.02). There was a good correlation between PMMR maceration score and the extent of maceration seen at conventional autopsy. This score may be useful in interpretation of fetal PMMR

  7. Current status of paediatric post-mortem imaging: an ESPR questionnaire-based survey

    Energy Technology Data Exchange (ETDEWEB)

    Arthurs, Owen J. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Radiology, London (United Kingdom); University College London, Institute of Child Health, London (United Kingdom); Rijn, Rick R. van [Academic Medical Centre, Department of Radiology, Amsterdam (Netherlands); Sebire, Neil J. [Great Ormond Street Hospital for Children, Department of Pathology, London (United Kingdom); University College London, Institute of Child Health, London (United Kingdom)

    2014-03-15

    The use of post-mortem imaging, including skeletal radiography, CT and MRI, is increasing, providing a minimally invasive alternative to conventional autopsy techniques. The development of clinical guidelines and national standards is being encouraged, particularly for cross-sectional techniques. To outline the current practice of post-mortem imaging amongst members of the European Society of Paediatric Radiology (ESPR). We e-mailed an online questionnaire of current post-mortem service provisions to members of the ESPR in January 2013. The survey included direct questions about what services were offered, the population imaged, current techniques used, imaging protocols, reporting experience and intended future involvement. Seventy-one percent (47/66) of centres from which surveys were returned reported performing some form of post-mortem imaging in children, of which 81 % perform radiographs, 51% CT and 38% MRI. Eighty-seven percent of the imaging is performed within the radiology or imaging departments, usually by radiographers (75%), and 89% is reported by radiologists, of which 64% is reported by paediatric radiologists. Overall, 72% of positive respondents have a standardised protocol for radiographs, but only 32% have such a protocol for CT and 27% for MRI. Sixty-one percent of respondents wrote that this is an important area that needs to be developed. Overall, the majority of centres provide some post-mortem imaging service, most of which is performed within an imaging department and reported by a paediatric radiologist. However, the populations imaged as well as the details of the services offered are highly variable among institutions and lack standardisation. We have identified people who would be interested in taking this work forwards. (orig.)

  8. Diagnostic accuracy of post-mortem magnetic resonance imaging in fetuses, children and adults: A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Thayyil, Sudhin, E-mail: s.thayyil@ucl.ac.u [Centre for Cardiovascular Imaging, UCL Institute of Child Health, London (United Kingdom); UCL Institute for Women' s Health, London (United Kingdom); Chandrasekaran, Manigandan [UCL Institute for Women' s Health, London (United Kingdom); Chitty, Lyn S. [UCL Institute for Women' s Health, London (United Kingdom); Clinical Molecular Genetics Unit, UCL Institute of Child Health, London (United Kingdom); Wade, Angie [Medical Statistics, UCL Institute of Child Health (United Kingdom); Skordis-Worrall, Jolene [Centre for International Health and Development, UCL Institute of Child Health (United Kingdom); Bennett-Britton, Ian [Centre for International Health and Development, UCL Institute of Child Health (United Kingdom); Health Economics and Financing Program, London School of Hygiene and Tropical Medicine, London (United Kingdom); Cohen, Marta [Department of Histopathology, Sheffield Children' s Hospital, Sheffield (United Kingdom); Withby, Elspeth [Department of Academic Radiology, Sheffield Children' s Hospital, Sheffield (United Kingdom); Sebire, Neil J. [Department of Histopathology, UCL Institute of Child Health and Great Ormond Street Hospital for Children, London (United Kingdom); Robertson, Nicola J. [UCL Institute for Women' s Health, London (United Kingdom); Taylor, Andrew M. [Centre for Cardiovascular Imaging, UCL Institute of Child Health, London (United Kingdom)

    2010-07-15

    To determine, in a systematic review, the diagnostic accuracy, acceptability and cost-effectiveness of less invasive autopsy by post-mortem MR imaging, in fetuses, children and adults. We searched Medline, Embase, the Cochrane library and reference lists to identify all studies comparing post-mortem MR imaging with conventional autopsy, published between January 1990 and March 2009. 539 abstracts were identified; 15 papers met the inclusion criteria; data from 9 studies were extracted (total: 146 fetuses, 11 children and 24 adults). In accurately identifying the final cause of death or most clinically significant abnormality, post-mortem MR imaging had a sensitivity and specificity of 69% (95% CI-56%, 80%) and 95% (95% CI-88%, 98%) in fetuses, and 28% (95% CI-13%, 47%) and 64% (95% CI-23%, 94%) in children and adults, respectively; however the published data is limited to small, heterogenous and poorly designed studies. Insufficient data is available on acceptability and economic evaluation of post-mortem MR imaging. Well designed, large, prospective studies are required to evaluate the accuracy of post-mortem MR imaging, before it can be offered as a clinical tool.

  9. Diagnostic accuracy of post-mortem magnetic resonance imaging in fetuses, children and adults: A systematic review

    International Nuclear Information System (INIS)

    Thayyil, Sudhin; Chandrasekaran, Manigandan; Chitty, Lyn S.; Wade, Angie; Skordis-Worrall, Jolene; Bennett-Britton, Ian; Cohen, Marta; Withby, Elspeth; Sebire, Neil J.; Robertson, Nicola J.; Taylor, Andrew M.

    2010-01-01

    To determine, in a systematic review, the diagnostic accuracy, acceptability and cost-effectiveness of less invasive autopsy by post-mortem MR imaging, in fetuses, children and adults. We searched Medline, Embase, the Cochrane library and reference lists to identify all studies comparing post-mortem MR imaging with conventional autopsy, published between January 1990 and March 2009. 539 abstracts were identified; 15 papers met the inclusion criteria; data from 9 studies were extracted (total: 146 fetuses, 11 children and 24 adults). In accurately identifying the final cause of death or most clinically significant abnormality, post-mortem MR imaging had a sensitivity and specificity of 69% (95% CI-56%, 80%) and 95% (95% CI-88%, 98%) in fetuses, and 28% (95% CI-13%, 47%) and 64% (95% CI-23%, 94%) in children and adults, respectively; however the published data is limited to small, heterogenous and poorly designed studies. Insufficient data is available on acceptability and economic evaluation of post-mortem MR imaging. Well designed, large, prospective studies are required to evaluate the accuracy of post-mortem MR imaging, before it can be offered as a clinical tool.

  10. Herpetic brainstem encephalitis: report of a post-mortem case studied electron microscopically and immunohisiochemically

    Directory of Open Access Journals (Sweden)

    José Eymard Homem Pitella

    1987-03-01

    Full Text Available A post-mortem examined case of herpetic brainstem encephalitis is presented. Clinically, the patient had cephalea followed by ataxia, drowsiness and multiple palsies of some cranial nerves, developing into death in eight days. The pathologic examination of the brain showed necrotizing encephalitis in multiple foci limited to the brainstem, more distinctly in the pons and medula oblongata. The technique of immunoperoxidase revealed rare glial cells with intranuclear immunoreactivity for herpes antigen. Rare viral particles with the morphological characteristics of the herpesvirus were identified in the nuclei of neurons in 10% formol fixed material. This is the second reported case of herpetic brainstem encephalitis confirmed by post-mortem examination. The pathway used by the virus to reach the central nervous system and its posterior dissemination to the oral cavity, the orbitofrontal region and the temporal lobes as well as to the brainstem, after a period of latency and reactivation, are discussed.

  11. Drowning - post-mortem imaging findings by computed tomography

    International Nuclear Information System (INIS)

    Christe, Andreas; Aghayev, Emin; Jackowski, Christian; Thali, Michael J.; Vock, Peter

    2008-01-01

    The aim of this study was to identify the classic autopsy signs of drowning in post-mortem multislice computed tomography (MSCT). Therefore, the post-mortem pre-autopsy MSCT- findings of ten drowning cases were correlated with autopsy and statistically compared with the post-mortem MSCT of 20 non-drowning cases. Fluid in the airways was present in all drowning cases. Central aspiration in either the trachea or the main bronchi was usually observed. Consecutive bronchospasm caused emphysema aquosum. Sixty percent of drowning cases showed a mosaic pattern of the lung parenchyma due to regions of hypo- and hyperperfused lung areas of aspiration. The resorption of fresh water in the lung resulted in hypodensity of the blood representing haemodilution and possible heart failure. Swallowed water distended the stomach and duodenum; and inflow of water filled the paranasal sinuses (100%). All the typical findings of drowning, except Paltau's spots, were detected using post-mortem MSCT, and a good correlation of MSCT and autopsy was found. The advantage of MSCT was the direct detection of bronchospasm, haemodilution and water in the paranasal sinus, which is rather complicated or impossible at the classical autopsy. (orig.)

  12. Post-mortem examination and sampling of African flamingos ...

    African Journals Online (AJOL)

    Recent largely unexplained deaths in African flamingos have prompted the need for standard, reproducible methods for the post-mortem examination of these birds, for the taking of samples and for the recording of findings. Here we describe suitable techniques and present three distinct protocols for field-based ...

  13. Stomach: ultrasonography evaluation and post mortem inspection in adult horses

    Directory of Open Access Journals (Sweden)

    Cristiano Chaves Pessoa da Veiga

    2014-06-01

    Full Text Available ABSTRACT. Veiga C.C.P., Cascon C.M., Souza B.G., Braga L.S.M., Souza V.C., Ferreira A.M.R. & Leite J.S. [Stomach: ultrasonography evaluation and post mortem inspection in adult horses.] Avaliação ultrassonográfica e anatomopatológica macroscópica do estômago de equinos destinados ao abate comercial. Revista Brasileira de Medicina Veterinária, 36(2:125-130, 2014. Instituto de Veterinária, Universidade Federal Rural do Rio de Janeiro, BR 465, km 7, Seropédica, 23890-000, RJ, Brasil. E-mail: radiovet@ufrrj.br The equine gastric ulcer syndrome (EGUS includes all symptomatic or asymptomatic cases of erosions, ulcers, gastritis, gastric emptying disorders, duodenitis, duodenal ulcers and complications of these disorders. Occupies a prominent place in the equine clinic where you can go for the death of the animal. Ultrasonography of the stomach is indicated when the animals showed clinical signs of gastric disease. The aim of this study was to describe the sonographic evaluation and macroscopic pathological findings of the stomach of adult horses intended for commercial slaughter. To this 39 intended for commercial slaughter horses were evaluated. Sonographic evaluation before slaughter transabdominal via the left side of abdomen for evaluation of the stomach was performed. After the slaughter of these animals their stomachs were collected, evaluated and photographed. The study concluded that ultrasonography identified the stomach in all animals evaluated, but did not allow a careful evaluation of the entire length of the viscera, especially the aglandular region and pleated border. All animals evaluated had injury to the gastric mucosa in different degrees. In animals evaluated, the stomach region was most affected by injuries glandular region, although the most severe lesions have been found in the ruffled border adjacent to aglandular region.

  14. CLINICAL PHARMACOLOGY OF DIURETICS

    Directory of Open Access Journals (Sweden)

    I. V. Soldatenko

    2014-06-01

    Full Text Available Clinical pharmacology of diuretics in the international system of ATC (anatomic-therapeutic-chemical is presented. Classification of this group by the action mechanism and caused effects is provided. Pharmacokinetics and pharmacodynamics features, indications and principles of diuretics usage in clinics are considered. Contraindications, side effects and interaction with other drugs of this group are discussed in detail.

  15. Optimisation of post mortem cardiac computed tomography compared to optical coherence tomography and histopathology - Technical note

    DEFF Research Database (Denmark)

    Falk, Erling

    2014-01-01

    . Here, a new method for optimising cardiac coronary CT with optical coherence tomography (OCT) and histopathology is presented. Materials and methods: Twenty human hearts obtained from autopsies were used. A contrast agent that solidifies after cooling was injected into the coronary arteries. CT...... of the images was also developed. Results: We have succeeded in developing a new method for post-mortem coronary CT angiography in which an autopsy heart is placed in a chest phantom to simulate clinical CT. Conclusion: The new method permits comparison of CT with OCT and histopathology. This method can also...

  16. Preliminary study of post mortem identification using lip prints.

    Science.gov (United States)

    Utsuno, Hajime; Kanoh, Takashi; Tadokoro, Osamu; Inoue, Katsuhiro

    2005-05-10

    Identification using lip prints was first performed in the 1950s and was the subject of much research in the 1960s and 70s, leading to the acceptance of this technique as evidence in the criminal justice system. Previous research has focused on identifying lip print types or on methods of obtaining hidden lip prints left at the crime scene. The present study aimed to clarify characteristics of lip prints from cadavers with various causes of death (including drowning and hanging) and to determine the effects of fixation on post mortem changes in lip impressions.

  17. Making post-mortem implantable cardioverter defibrillator explantation safe

    DEFF Research Database (Denmark)

    Räder, Sune B E W; Zeijlemaker, Volkert; Pehrson, Steen

    2009-01-01

    that the resting voltage over the operating person would not exceed 50 V. CONCLUSION: The use of intact medical gloves made of latex, neoprene, or plastic eliminates the potential electrical risk during explantation of an ICD. Two gloves on each hand offer sufficient protection. We will recommend the use......AIMS: The aim of this study is to investigate whether protection with rubber or plastic gloves during post-mortem explantation of an implantable cardioverter defibrillator (ICD) offers enough protection for the explanting operator during a worst-case scenario (i.e. ICD shock). METHODS AND RESULTS...

  18. Diagnostic accuracy of post-mortem CT with targeted coronary angiography versus autopsy for coroner-requested post-mortem investigations: a prospective, masked, comparison study.

    Science.gov (United States)

    Rutty, Guy N; Morgan, Bruno; Robinson, Claire; Raj, Vimal; Pakkal, Mini; Amoroso, Jasmin; Visser, Theresa; Saunders, Sarah; Biggs, Mike; Hollingbury, Frances; McGregor, Angus; West, Kevin; Richards, Cathy; Brown, Laurence; Harrison, Rebecca; Hew, Roger

    2017-07-08

    England and Wales have one of the highest frequencies of autopsy in the world. Implementation of post-mortem CT (PMCT), enhanced with targeted coronary angiography (PMCTA), in adults to avoid invasive autopsy would have cultural, religious, and potential economic benefits. We aimed to assess the diagnostic accuracy of PMCTA as a first-line technique in post-mortem investigations. In this single-centre (Leicester, UK), prospective, controlled study, we selected cases of natural and non-suspicious unnatural death referred to Her Majesty's (HM) Coroners. We excluded cases younger than 18 years, known to have had a transmittable disease, or who weighed more than 125 kg. Each case was assessed by PMCTA, followed by autopsy. Pathologists were masked to the PMCTA findings, unless a potential risk was shown. The primary endpoint was the accuracy of the cause of death diagnosis from PMCTA against a gold standard of autopsy findings, modified by PMCTA findings only if additional substantially incontrovertible findings were identified. Between Jan 20, 2010, and Sept 13, 2012, we selected 241 cases, for which PMCTA was successful in 204 (85%). Seven cases were excluded from the analysis because of procedural unmasking or no autopsy data, as were 24 cases with a clear diagnosis of traumatic death before investigation; 210 cases were included. In 40 (19%) cases, predictable toxicology or histology testing accessible by PMCT informed the result. PMCTA provided a cause of death in 193 (92%) cases. A major discrepancy with the gold standard was noted in 12 (6%) cases identified by PMCTA, and in nine (5%) cases identified by autopsy (because of specific findings on PMCTA). The frequency of autopsy and PMCTA discrepancies were not significantly different (p=0·65 for major discrepancies and p=0·21 for minor discrepancies). Cause of death given by PMCTA did not overlook clinically significant trauma, occupational lung disease, or reportable disease, and did not significantly affect

  19. Method for modeling post-mortem biometric 3D fingerprints

    Science.gov (United States)

    Rajeev, Srijith; Shreyas, Kamath K. M.; Agaian, Sos S.

    2016-05-01

    Despite the advancements of fingerprint recognition in 2-D and 3-D domain, authenticating deformed/post-mortem fingerprints continue to be an important challenge. Prior cleansing and reconditioning of the deceased finger is required before acquisition of the fingerprint. The victim's finger needs to be precisely and carefully operated by a medium to record the fingerprint impression. This process may damage the structure of the finger, which subsequently leads to higher false rejection rates. This paper proposes a non-invasive method to perform 3-D deformed/post-mortem finger modeling, which produces a 2-D rolled equivalent fingerprint for automated verification. The presented novel modeling method involves masking, filtering, and unrolling. Computer simulations were conducted on finger models with different depth variations obtained from Flashscan3D LLC. Results illustrate that the modeling scheme provides a viable 2-D fingerprint of deformed models for automated verification. The quality and adaptability of the obtained unrolled 2-D fingerprints were analyzed using NIST fingerprint software. Eventually, the presented method could be extended to other biometric traits such as palm, foot, tongue etc. for security and administrative applications.

  20. Post-mortem MRI of the foetal spine and spinal cord

    International Nuclear Information System (INIS)

    Widjaja, E.; Whitby, E.H.; Cohen, M.; Paley, M.N.J.; Griffiths, P.D.

    2006-01-01

    Aims: To compare the findings of post-mortem magnetic resonance imaging (MRI) of the foetal spine with autopsy with a view to using post-mortem MRI as an alternative or adjunct to autopsy, particularly in foetal and neonatal cases. Materials and Methods: The brains and spines of 41 foetuses, with a gestational age range of 14-41 weeks, underwent post-mortem MRI before autopsy. Post-mortem MRI of the brain consisted of T2-weighted sequences in three orthogonal planes and MRI of the spine consisted of T2-weighted sequence in the sagittal and axial planes in all cases and coronal planes in selected cases. Results: Thirty of 41 (78%) foetal spines were found to be normal at autopsy and on post-mortem MRI. Eleven of 41 (22%) foetal spines were abnormal: eight foetuses had myelomeningocoeles and Chiari 2 deformities, one foetus had limited dorsal myeloschisis, one foetus had caudal regression syndrome, and one had diastematomyelia. The post-mortem MRI findings concurred with the autopsy findings in 10/11 of the abnormal cases, the disagreement being the case of diastematomyelia that was shown on post-mortem MRI but was not diagnosed at autopsy. Conclusions: In this series, post-mortem MRI findings agreed with the autopsy findings in 40/41(98%) cases and in one case the post-mortem MRI demonstrated an abnormality not demonstrated at autopsy

  1. Multimodal imaging and in vivo/post mortem co-registration in rodents and non human primates

    International Nuclear Information System (INIS)

    Delzescaux, T.

    2006-01-01

    Within the framework of neuro-degenerative disease studies, animal models still remain essential for the improvement of our understanding of underlying pathological mechanisms and for the discovery and development of potential novel therapeutic approaches. The pre-clinical research especially requires the use of non-human primates models because of the similarities between their brain and Human's, whereas fundamental investigations in many areas of biology and medicine more widely involve the use of rodent models.The recent developments of in vivo imaging systems dedicated to small animals (μ-CT, μ-MRI and μ-PET) have made possible the study of brain anatomic alterations as well as the longitudinal follow-up of metabolism and neurotransmission impairments, which can be involved in neuro-degenerative diseases. In particular, μ-PET is becoming increasingly relevant to assess the efficiency of a potential candidate in the field of drug discovery and development and disease diagnosis. However, until today a few laboratories are equipped with them. Moreover, their limited spatial resolution and the lack of specific biological markers are still major limitations. As a consequence, the scientific community still needs comparative anatomical and/or functional analyses, in particular for studies concerning rodent brain. Hence, post mortem biological imaging remains the powerful, reference and predominantly technology used for small animal imaging and for the validation of in vivo imaging systems. Generally, anatomical and complementary functional information are, respectively, provided by histological staining and autoradiography of corresponding brain sections. The large variety of histological dyes (cresyl violet for Nissl bodies Congo red for amyloid plaques) and radioactive compounds ([ 14 C]Deoxyglucose for cerebral glucose metabolism, [ 14 C]leucine for cerebral protein synthesis [ 14 C]iodoantipyrine for cerebral blood flow), as well as the microscopic range of

  2. Multimodal imaging and in vivo/post mortem co-registration in rodents and non human primates

    Energy Technology Data Exchange (ETDEWEB)

    Delzescaux, T. [Service Hospitalier Frederic Joliot, Isotopic Imaging, 91 - Orsay (France)

    2006-07-01

    Within the framework of neuro-degenerative disease studies, animal models still remain essential for the improvement of our understanding of underlying pathological mechanisms and for the discovery and development of potential novel therapeutic approaches. The pre-clinical research especially requires the use of non-human primates models because of the similarities between their brain and Human's, whereas fundamental investigations in many areas of biology and medicine more widely involve the use of rodent models.The recent developments of in vivo imaging systems dedicated to small animals ({mu}-CT, {mu}-MRI and {mu}-PET) have made possible the study of brain anatomic alterations as well as the longitudinal follow-up of metabolism and neurotransmission impairments, which can be involved in neuro-degenerative diseases. In particular, {mu}-PET is becoming increasingly relevant to assess the efficiency of a potential candidate in the field of drug discovery and development and disease diagnosis. However, until today a few laboratories are equipped with them. Moreover, their limited spatial resolution and the lack of specific biological markers are still major limitations. As a consequence, the scientific community still needs comparative anatomical and/or functional analyses, in particular for studies concerning rodent brain. Hence, post mortem biological imaging remains the powerful, reference and predominantly technology used for small animal imaging and for the validation of in vivo imaging systems. Generally, anatomical and complementary functional information are, respectively, provided by histological staining and autoradiography of corresponding brain sections. The large variety of histological dyes (cresyl violet for Nissl bodies Congo red for amyloid plaques) and radioactive compounds ([{sup 14}C]Deoxyglucose for cerebral glucose metabolism, [{sup 14}C]leucine for cerebral protein synthesis [{sup 14}C]iodoantipyrine for cerebral blood flow), as well as

  3. Optimising imaging parameters for post mortem MR imaging of the human brain

    Energy Technology Data Exchange (ETDEWEB)

    Blamire, A.M.; Rowe, J.G.; Styles, P. [MRC Magnetic Resonance Spectroscopy Unit, Dept. of Biochemistry, Univ. of Oxford (United Kingdom); McDonald, B. [MRC Schizophrenia Research Group, Dept. of Neuropathology, Radcliffe Infirmary, Oxford (United Kingdom)

    1999-11-01

    Purpose: MR imaging of post mortem brains has the potential to yield volumetric information and define the extent of structural changes prior to pathological examination. Although standard T2-weighted clinical imaging sequences have been used for the examination of formalin-fixed brains, these protocols may not yield optimum contrast. We examined the effect of varying durations of formalin fixation on the transverse relaxation time (T2) and the tissue spin density. Material and Methods: Three post mortem brains were examined weekly during formalin fixation from the unfixed state to 35 days fixation. Standard MR spin-echo imaging was used at 5 echo times (20-100 ms) to calculate transverse relaxation time (T2) and spin density. Results: T2 decreased significantly (ANOVA, p<0.001) in both grey and white matter by 7 days fixation and there was a further (but non-significant) trend towards lower values between7 and 35 days. Grey and white matter T2 times converged with fixation. Conversely, the grey to white matter spin density ratio increased from 1.19{+-}0.01 to 1.54{+-}0.06 over five weeks of fixation. Conclusion: Our results suggest that spin density-weighted imaging sequences would provide improved grey to white matter contrast over T2-weighted sequences. (orig.)

  4. Note sulla concezione del post mortem presso gli Ittiti

    DEFF Research Database (Denmark)

    Vigo, Matteo; Bellucci, Benedetta

    significato escatologico della morte; 2) la definizione dello status ultraterreno dei defunti (i.e. il diverso trattamento del defunto, ad esempio dal punto di vista cultuale, sulla base della sua condizione sociale); 3) il delineamento dei caratteri e delle funzioni delle divinità ultra-terrene; 4) la......Oggetto d’analisi di questo paper è la concezione della sfera del post-mortem presso la civiltà degli Ittiti. Lo studio delle tematiche che riguardano la concezione dell’“aldilà” nel mondo ittita, sia in senso fisico che metafisico, riveste una larga importanza nella letteratura ittitologica ed è...... stato, pertanto, diffusamente trattato. Nel presente contributo si è scelto quindi di approfondire solo alcuni aspetti della concezione dell’oltretomba, inteso come dimensione metafisica in cui il corpo del defunto giace, staziona o transita dopo la morte. I temi approfonditi saranno quindi: 1) il...

  5. Post-mortem virtual estimation of free abdominal blood volume

    International Nuclear Information System (INIS)

    Ampanozi, Garyfalia; Hatch, Gary M.; Ruder, Thomas D.; Flach, Patricia M.; Germerott, Tanja; Thali, Michael J.; Ebert, Lars C.

    2012-01-01

    Purpose: The purpose of this retrospective study was to examine the reliability of virtually estimated abdominal blood volume using segmentation from postmortem computed tomography (PMCT) data. Materials and methods: Twenty-one cases with free abdominal blood were investigated by PMCT and autopsy. The volume of the blood was estimated using a manual segmentation technique (Amira, Visage Imaging, Germany) and the results were compared to autopsy data. Six of 21 cases had undergone additional post-mortem computed tomographic angiography (PMCTA). Results: The virtually estimated abdominal blood volumes did not differ significantly from those measured at autopsy. Additional PMCTA did not bias data significantly. Conclusion: Virtual estimation of abdominal blood volume is a reliable technique. The virtual blood volume estimation is a useful tool to deliver additional information in cases where autopsy is not performed or in cases where a postmortem angiography is performed

  6. The Elusive Universal Post-Mortem Interval Formula

    Energy Technology Data Exchange (ETDEWEB)

    Vass, Arpad Alexander [ORNL

    2011-01-01

    The following manuscript details our initial attempt at developing universal post-mortem interval formulas describing human decomposition. These formulas are empirically derived from data collected over the last 20 years from the University of Tennessee's Anthropology Research Facility, in Knoxville, Tennessee, USA. Two formulas were developed (surface decomposition and burial decomposition) based on temperature, moisture, and the partial pressure of oxygen, as being three of the four primary drivers for human decomposition. It is hoped that worldwide application of these formulas to environments and situations not readily studied in Tennessee will result in interdisciplinary cooperation between scientists and law enforcement personnel that will allow for future refinements of these models leading to increased accuracy.

  7. Post-mortem toxicology in young sudden cardiac death victims

    DEFF Research Database (Denmark)

    Bjune, Thea; Risgaard, Bjarke; Kruckow, Line

    2017-01-01

    Aims: Several drugs increase the risk of ventricular fibrillation and sudden cardiac death (SCD). We aimed to investigate in detail the toxicological findings of all young SCD throughout Denmark. Methods and results: Deaths in persons aged 1-49 years were included over a 10-year period. Death...... certificates and autopsy reports were retrieved and read to identify cases of sudden death and establish cause of death. All medico-legal autopsied SCD were included and toxicological reports collected. Positive toxicology was defined as the presence of any substance (licit and/or illicit). All toxicological...... findings had previously been evaluated not to have caused the death (i.e. lethal concentrations were excluded). We identified 620 medico-legal autopsied cases of SCD, of which 77% (n = 477) were toxicologically investigated post-mortem, and 57% (n = 270) had a positive toxicology profile. Sudden cardiac...

  8. Essentials of forensic post-mortem MR imaging in adults

    Science.gov (United States)

    Ruder, T D; Thali, M J; Hatch, G M

    2014-01-01

    Post-mortem MR (PMMR) imaging is a powerful diagnostic tool with a wide scope in forensic radiology. In the past 20 years, PMMR has been used as both an adjunct and an alternative to autopsy. The role of PMMR in forensic death investigations largely depends on the rules and habits of local jurisdictions, availability of experts, financial resources, and individual case circumstances. PMMR images are affected by post-mortem changes, including position-dependent sedimentation, variable body temperature and decomposition. Investigators must be familiar with the appearance of normal findings on PMMR to distinguish them from disease or injury. Coronal whole-body images provide a comprehensive overview. Notably, short tau inversion–recovery (STIR) images enable investigators to screen for pathological fluid accumulation, to which we refer as “forensic sentinel sign”. If scan time is short, subsequent PMMR imaging may be focussed on regions with a positive forensic sentinel sign. PMMR offers excellent anatomical detail and is especially useful to visualize pathologies of the brain, heart, subcutaneous fat tissue and abdominal organs. PMMR may also be used to document skeletal injury. Cardiovascular imaging is a core area of PMMR imaging and growing evidence indicates that PMMR is able to detect ischaemic injury at an earlier stage than traditional autopsy and routine histology. The aim of this review is to present an overview of normal findings on forensic PMMR, provide general advice on the application of PMMR and summarise the current literature on PMMR imaging of the head and neck, cardiovascular system, abdomen and musculoskeletal system. PMID:24191122

  9. Post mortem magnetic resonance imaging in the fetus, infant and child: A comparative study with conventional autopsy (MaRIAS Protocol

    Directory of Open Access Journals (Sweden)

    Thayyil Sudhin

    2011-12-01

    Full Text Available Abstract Background Minimally invasive autopsy by post mortem magnetic resonance (MR imaging has been suggested as an alternative for conventional autopsy in view of the declining consented autopsy rates. However, large prospective studies rigorously evaluating the accuracy of such an approach are lacking. We intend to compare the accuracy of a minimally invasive autopsy approach using post mortem MR imaging with that of conventional autopsy in fetuses, newborns and children for detection of the major pathological abnormalities and/or determination of the cause of death. Methods/Design We recruited 400 consecutive fetuses, newborns and children referred for conventional autopsy to one of the two participating hospitals over a three-year period. We acquired whole body post mortem MR imaging using a 1.5 T MR scanner (Avanto, Siemens Medical Solutions, Enlargen, Germany prior to autopsy. The total scan time varied between 90 to 120 minutes. Each MR image was reported by a team of four specialist radiologists (paediatric neuroradiology, paediatric cardiology, paediatric chest & abdominal imaging and musculoskeletal imaging, blinded to the autopsy data. Conventional autopsy was performed according to the guidelines set down by the Royal College of Pathologists (UK by experienced paediatric or perinatal pathologists, blinded to the MR data. The MR and autopsy data were recorded using predefined categorical variables by an independent person. Discussion Using conventional post mortem as the gold standard comparator, the MR images will be assessed for accuracy of the anatomical morphology, associated lesions, clinical usefulness of information and determination of the cause of death. The sensitivities, specificities and predictive values of post mortem MR alone and MR imaging along with other minimally invasive post mortem investigations will be presented for the final diagnosis, broad diagnostic categories and for specific diagnosis of each system

  10. Usefulness of post-mortem ophthalmological endoscopy during forensic autopsy: a case report.

    Science.gov (United States)

    Tsujinaka, Masatake; Akaza, Kayoko; Nagai, Atsushi; Nakamura, Isao; Bunai, Yasuo

    2005-01-01

    Post-mortem intraocular findings in two autopsy cases with traumatic intracranial haemorrhage were obtained using an ophthalmological endoscope. The endoscopy results clearly revealed the presence of intraocular haemorrhages and papilledema caused by intracranial haemorrhage. Post-mortem ophthalmological endoscopy offers several benefits. First, post-mortem intraocular findings can be directly observed in corpses with post-mortem clouding of the cornea. Secondly, the endoscopy only requires a 0.9 mm incision in the sclera and does not require the removal of the eye from the corpse, a procedure that should be avoided for ethical and cosmetic reasons. Thus, post-mortem opthalmological endoscopy is a useful method for obtaining intraocular findings in autopsies.

  11. Small vessel disease, neurovascular regulation and cognitive impairment: post-mortem studies reveal a complex relationship, still poorly understood.

    Science.gov (United States)

    Love, Seth; Miners, J Scott

    2017-07-15

    The contribution of vascular disease to cognitive impairment is under-recognized and the pathogenesis is poorly understood. This information gap has multiple causes, including a lack of post-mortem validation of clinical diagnoses of vascular cognitive impairment (VCI) or vascular dementia (VaD), the exclusion of cases with concomitant neurodegenerative disease when diagnosing VCI/VaD, and a lack of standardization of neuropathological assessment protocols for vascular disease. Other contributors include a focus on end-stage destructive lesions to the exclusion of more subtle types of diffuse brain injury, on structural abnormalities of arteries and arterioles to the exclusion of non-structural abnormalities and capillary damage, and the use of post-mortem sampling strategies that are biased towards the identification of neurodegenerative pathologies. Recent studies have demonstrated the value of detailed neuropathology in characterizing vascular contributions to cognitive impairment (e.g. in diabetes), and highlight the importance of diffuse white matter changes, capillary damage and vasoregulatory abnormalities in VCI/VaD. The use of standardized, evidence-based post-mortem assessment protocols and the inclusion of biochemical as well as morphological methods in neuropathological studies should improve the accuracy of determination of the contribution of vascular disease to cognitive impairment and clarify the relative contribution of different pathogenic processes to the tissue damage. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  12. Post-mortem diagnostics in cases of sepsis. Part 1. Aetiology, epidemiology and microbiological tests

    Directory of Open Access Journals (Sweden)

    Marta Rorat

    2015-03-01

    Full Text Available Clinical practice has an effective methodology of diagnostic procedures to be followed in cases of sepsis. However, there are as yet no corresponding standards of action in post-mortem diagnostics. The scope of examinations is limited to an autopsy and histopathological tests. This situation may lead to errors in medico-legal opinions on the cause of death and in the assessment of appropriateness of medical procedures. In cases of suspected sepsis, medico-legal investigations require obtaining detailed information about the circumstances of death (including symptoms and results of intravital examinations before autopsy is performed, as well as sterile collection of specimens for microbiological tests and interpretation of their results on the basis of knowledge of epidemiology, pathophysiology and clinical progression of sepsis.

  13. Lipoma of the midbrain: post-mortem finding in a patient with breast cancer

    Directory of Open Access Journals (Sweden)

    Verônica Maia Gouvea

    1989-09-01

    Full Text Available Intracranial lipomas are rare, usually do not have clinical expression and are located mare frequently in the corpus callosum. Other locations include the spinal cord, midbrain tectum, superior vermis, tuber cinereum, infundibulum and more rarely cerebellopontine angle, hypothalamus, superior medullary velum and insula. We report the case of a lipoma of the left inferior colliculus which was a post-mortem finding in a woman who died of breast cancer. Although there are reports of intracranial lipomas in patients with malignant tumors there is no explanation for the co-existence of the two tumors. The present tumor also includes a segment of a nerve which is not uncommon, but a less common finding was the presence of nests of Schwann cells within it, shown by immunohistochemistry.

  14. Post-mortem cytogenomic investigations in patients with congenital malformations.

    Science.gov (United States)

    Dias, Alexandre Torchio; Zanardo, Évelin Aline; Dutra, Roberta Lelis; Piazzon, Flavia Balbo; Novo-Filho, Gil Monteiro; Montenegro, Marilia Moreira; Nascimento, Amom Mendes; Rocha, Mariana; Madia, Fabricia Andreia Rosa; Costa, Thais Virgínia Moura Machado; Milani, Cintia; Schultz, Regina; Gonçalves, Fernanda Toledo; Fridman, Cintia; Yamamoto, Guilherme Lopes; Bertola, Débora Romeo; Kim, Chong Ae; Kulikowski, Leslie Domenici

    2016-08-01

    Congenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), microsatellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin-embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p11.32); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C>G (c.746C>G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. O líquido cefalorraqueano no post-mortem

    Directory of Open Access Journals (Sweden)

    A. Spina-França

    1969-12-01

    Full Text Available Foi estudado o LCR de 45 cadáveres, sendo os resultados considerados em função do tempo decorrido entre o momento da morte e a colheita do LCR (TOC. Obedecendo a esse critério os casos foram assim grupados: 1 aqueles com TOC até 4 horas; 2 aqueles com TOC de 4 a 8 horas; 3 aqueles com TOC de 8 horas ou mais. Com o aumento do TOC a presença de hemácias no LCR de cadáveres se torna mais freqüente e mais intensa. A mistura de sangue ao LCR prejudica a avaliação das modificações cadavéricas de outros componentes do LCR, conforme foi demonstrado para as concentrações de cloretos glicose e proteínas totais, para o perfil protêico e para a atividade de transaminases. Assim sendo, para avaliar as modificações da composição do LCR próprias ao post-mortem devem ser considerados apenas os casos com menos de 1000 hemácias/mm³. O número normal de leucócitos foi proporcionalmente mais comum nas amostras provenientes de cadáveres cujo TOC era igual ou superior a 8 horas. A pleocitose foi observada com mais freqüência que o número normal de leucócitos, sendo mais comumente ligeira ou discreta. Quantidades superiores a 50 leucócitos/mm³ foram observadas geralmente em casos relativos a pacientes que faleceram na vigência de processos infecciosos agudos. As concentrações de cloretos e de glicose no LCR tendem a cair no postmortem e as diminuições mostraram-se, em média, tanto mais intensas quanto maior o TOC. A hipoglicorraquia foi, em média mais acentuada nos casos com pleoeitose mais intensa. A concentração de uréia tende a elevar-se de modo precoce, não tendo sido encontradas médias significativamente diversas em função do TOC. A atividade de TGO tende a elevar-se no post-mortem sendo esta elevação, em média, mais nítida a partir do grupo de casos com TOC de 4 até 8 horas. Ocorre também tendência a aumento da atividade de TGP; esta se mostrou menos intensa que a de TGO e, em média, foi mais nítida a

  16. Clarke's Isolation and identification of drugs in pharmaceuticals, body fluids, and post-mortem material

    National Research Council Canada - National Science Library

    Clarke, E. G. C; Moffat, A. C; Jackson, J. V

    1986-01-01

    This book is intended for scientists faced with the difficult problem of identifying an unknown drug in a pharmaceutical product, in a sample of tissue or body fluid from a living patient, or in post-mortem material...

  17. Post-mortem whole-body magnetic resonance imaging of human fetuses: a comparison of 3-T vs. 1.5-T MR imaging with classical autopsy

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Xin; Bevilacqua, Elisa; Cos Sanchez, Teresa; Jani, Jacques C. [University Hospital Brugmann, Universite Libre de Bruxelles, Department of Obstetrics and Gynecology, Fetal Medicine Unit, Brussels (Belgium); Cannie, Mieke M. [University Hospital Brugmann, Universite Libre de Bruxelles, Department of Radiology, Brussels (Belgium); Vrije Universiteit Brussel, Department of Radiology, UZ Brussel, Brussels (Belgium); Arthurs, Owen J.; Sebire, Neil J. [Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); UCL Institute of Child Health, London (United Kingdom); Segers, Valerie; Fourneau, Catherine [University Hospital Brugmann, Universite Libre de Bruxelles, Department of Fetopathology, Brussels (Belgium)

    2017-08-15

    To prospectively compare diagnostic accuracy of fetal post-mortem whole-body MRI at 3-T vs. 1.5-T. Between 2012 and 2015, post-mortem MRI at 1.5-T and 3-T was performed in fetuses after miscarriage/stillbirth or termination. Clinical MRI diagnoses were assessed using a confidence diagnostic score and compared with classical autopsy to derive a diagnostic error score. The relation of diagnostic error for each organ group with gestational age was calculated and 1.5-T with 3-T was compared with accuracy analysis. 135 fetuses at 12-41 weeks underwent post-mortem MRI (followed by conventional autopsy in 92 fetuses). For all organ groups except the brain, and for both modalities, the diagnostic error decreased with gestation (P < 0.0001). 3-T MRI diagnostic error was significantly lower than that of 1.5-T for all anatomic structures and organ groups, except the orbits and brain. This difference was maintained for fetuses <20 weeks gestation. Moreover, 3-T was associated with fewer non-diagnostic scans and greater concordance with classical autopsy than 1.5-T MRI, especially for the thorax, heart and abdomen in fetuses <20 weeks. Post-mortem fetal 3-T MRI improves confidence scores and overall accuracy compared with 1.5-T, mainly for the thorax, heart and abdomen of fetuses <20 weeks of gestation. (orig.)

  18. Post-Mortem Projections: Medieval Mystical Resurrection and the Return of Tupac Shakur

    OpenAIRE

    Spencer-Hall, Alicia

    2012-01-01

    Medieval hagiographies abound with tales of post-mortem visits and miracles by saints. The saint was a powerful religious individual both in life and in death, a conduit of divine grace and lightning rod for Christian fervour. With her post-mortem presence, the presumptive boundary between living and dead, spirit and flesh, is rent apart: showing the reality of the hereafter and shattering the fantasies of the mortal world. The phenomenon of a glorified individual returning to a worshipful co...

  19. Post-Mortem Projections: Medieval Mystical Resurrection and the Return of Tupac Shakur

    OpenAIRE

    Spencer-Hall, A.

    2012-01-01

    Medieval hagiographies abound with tales of post-mortem visits and miracles by saints. The saint was a powerful religious individual both in life and in death, a conduit of divine grace and lightning rod for Christian fervour. With her post-mortem presence, the presumptive boundary between living and dead, spirit and flesh, is rent apart: showing the reality of the hereafter and shattering the fantasies of the mortal world. The phenomenon of a glorified individual returning to ...

  20. O líquido cefalorraqueano no post-mortem The cerebrospinal fluid in the post-mortem

    Directory of Open Access Journals (Sweden)

    A. Spina-França

    1969-12-01

    Full Text Available Foi estudado o LCR de 45 cadáveres, sendo os resultados considerados em função do tempo decorrido entre o momento da morte e a colheita do LCR (TOC. Obedecendo a esse critério os casos foram assim grupados: 1 aqueles com TOC até 4 horas; 2 aqueles com TOC de 4 a 8 horas; 3 aqueles com TOC de 8 horas ou mais. Com o aumento do TOC a presença de hemácias no LCR de cadáveres se torna mais freqüente e mais intensa. A mistura de sangue ao LCR prejudica a avaliação das modificações cadavéricas de outros componentes do LCR, conforme foi demonstrado para as concentrações de cloretos glicose e proteínas totais, para o perfil protêico e para a atividade de transaminases. Assim sendo, para avaliar as modificações da composição do LCR próprias ao post-mortem devem ser considerados apenas os casos com menos de 1000 hemácias/mm³. O número normal de leucócitos foi proporcionalmente mais comum nas amostras provenientes de cadáveres cujo TOC era igual ou superior a 8 horas. A pleocitose foi observada com mais freqüência que o número normal de leucócitos, sendo mais comumente ligeira ou discreta. Quantidades superiores a 50 leucócitos/mm³ foram observadas geralmente em casos relativos a pacientes que faleceram na vigência de processos infecciosos agudos. As concentrações de cloretos e de glicose no LCR tendem a cair no postmortem e as diminuições mostraram-se, em média, tanto mais intensas quanto maior o TOC. A hipoglicorraquia foi, em média mais acentuada nos casos com pleoeitose mais intensa. A concentração de uréia tende a elevar-se de modo precoce, não tendo sido encontradas médias significativamente diversas em função do TOC. A atividade de TGO tende a elevar-se no post-mortem sendo esta elevação, em média, mais nítida a partir do grupo de casos com TOC de 4 até 8 horas. Ocorre também tendência a aumento da atividade de TGP; esta se mostrou menos intensa que a de TGO e, em média, foi mais nítida a

  1. Post-mortem imaging compared with autopsy in trauma victims--A systematic review.

    Science.gov (United States)

    Jalalzadeh, Hamid; Giannakopoulos, Georgios F; Berger, Ferco H; Fronczek, Judith; van de Goot, Frank R W; Reijnders, Udo J; Zuidema, Wietse P

    2015-12-01

    Post-mortem imaging or virtual autopsy is a rapidly advancing field of post-mortem investigations of trauma victims. In this review we evaluate the feasibility of complementation or replacement of conventional autopsy by post-mortem imaging in trauma victims. A systematic review was performed in compliance with the PRISMA guidelines. MEDLINE, Embase and Cochrane databases were systematically searched for studies published between January 2008 and January 2014, in which post-mortem imaging was compared to conventional autopsy in trauma victims. Studies were included when two or more trauma victims were investigated. Twenty-six studies were included, with a total number of 563 trauma victims. Post-mortem computer tomography (PMCT) was performed in 22 studies, post-mortem magnetic resonance imaging (PMMRI) in five studies and conventional radiography in two studies. PMCT and PMMRI both demonstrate moderate to high-grade injuries and cause of death accurately. PMCT is more sensitive than conventional autopsy or PMMRI in detecting skeletal injuries. For detecting minor organ and soft tissue injuries, autopsy remains superior to imaging. Aortic injuries are missed frequently by PMCT and PMMRI and form their main limitation. PMCT should be considered as an essential supplement to conventional autopsy in trauma victims since it detects many additional injuries. Despite some major limitations, PMCT could be used as an alternative for conventional autopsy in situations where conventional autopsy is rejected or unavailable. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Forensic radiology: The role of cross-sectional imaging in virtual post-mortem examinations

    International Nuclear Information System (INIS)

    Higginbotham-Jones, Joshua; Ward, Anthony

    2014-01-01

    Aim: The aim of this review is to assess the benefits and limitations of using Multi Slice Computed Tomography and Magnetic Resonance as non-invasive post-mortem imaging methods. Method: The author utilised SciVerse (Science Direct), Scopus, PubMed and Discover to search for relevant articles. The following search terms were used: virtopsy, minimally invasive post-mortem imaging, autopsy, Multi Slice Computed Tomography, Magnetic Resonance. Articles which discussed the use of non-invasive imaging techniques for post-mortem examinations were included in the review. Any articles published before 2003 were excluded with a few exceptions. Findings: The decline in use of the conventional post-mortem method has led to the need for an alternative method of investigation which increases both sensitivity and specificity, and also is more acceptable to the family of the deceased. Discussion/conclusion: There are numerous factors affecting the usability of these non-invasive post-mortem options including cost and availability. With the price of non-invasive post-mortem examinations often rising above £1000, it is considered to be less economically viable than the conventional method. Therefore, further research into this method and its implementation in hospitals has been delayed

  3. Causes of Stillbirth and Time of Death in Swedish Holstein Calves Examined Post Mortem

    Directory of Open Access Journals (Sweden)

    Elvander M

    2003-09-01

    Full Text Available This study was initiated due to the observation of increasing and rather high levels of stillbirths, especially in first-calving Swedish Holstein cows (10.3%, 2002. Seventy-six Swedish Holstein calves born to heifers at 41 different farms were post mortem examined in order to investigate possible reasons for stillbirth and at what time in relation to full-term gestation they had occurred. The definition of a stillborn calf was dead at birth or within 24 h after birth after at least 260 days of gestation. Eight calves were considered as having died already in uterus. Slightly less than half of the examined calves (46.1% were classified as having died due to a difficult calving. Four calves (5.3% had different kinds of malformations (heart defects, enlarged thymus, urine bladder defect. Approximately one third of the calves (31.6% were clinically normal at full-term with no signs of malformation and born with no indication of difficulties at parturition or any other reason that could explain the stillbirth. The numbers of male and female calves were rather equally distributed within the groups. A wide variation in post mortem weights was seen in all groups, although a number of the calves in the group of clinically normal calves with unexplained reason of death were rather small and, compared with e.g. those calves categorised as having died due to a difficult calving, their average birth weight was 6 kg lower (39.9 ± 1.7 kg vs. 45.9 ± 1.5 kg, p ≤ 0.01. It was concluded that the cause of stillbirth with a non-infectious aetiology is likely to be multifactorial and difficult calving may explain only about half of the stillbirths. As much as one third of the calves seemed clinically normal with no obvious reason for death. This is a target group of calves that warrants a more thorough investigation in further studies.

  4. Clinical pharmacology of homoharringtonine

    International Nuclear Information System (INIS)

    Savaraj, N.; Lu, K.; Dimery, I.; Feun, L.G.; Burgess, M.; Keating, M.; Loo, T.L.

    1986-01-01

    Clinical pharmacokinetics of homoharringtonine (HHT) were studied in eight patients who received uniformly labeled HHT at 3-4 mg/m2 (150 mu Ci) by continuous 6-hour infusion. The drug and metabolites were quantified by radiochemical and high-performance liquid chromatographic techniques. Computerized nonlinear least-square regression and curve stripping were used to characterize HHT and total [ 3 H]HHT equivalent pharmacokinetics. Unchanged HHT in the plasma declined biphasically, with an alpha-half-life of 0.5 +/- 0.1 hours and a beta-half-life of 9.3 +/- 1.4 hours. The total clearance of HHT was 177.4 +/- 27.7 ml X hour-1 X kg-1, and the apparent volume of distribution, estimated from the area under the drug concentration versus time curve, was 2.4 +/- 0.4 L X kg-1. Correspondingly, the total [ 3 H]HHT equivalent disappeared from the plasma in a triphasic manner. Compared with the pharmacokinetic parameters of unchanged HHT, the terminal half-life of total 3 H was 67.5 +/- 7.5 hours, 7.4 times longer; the total clearance was 30.9 +/- 3.1 ml X hour-1 X kg-1, 5.5 times slower; but the volume of distribution by area was 2.7 +/- 0.1 L X kg-1, nearly the same. The 72-hour cumulative urinary excretion of total tritium was 28.2% of the administered dose and only 38.3% of this resided in unchanged HHT. Thus, urinary excretion was not a major route of elimination of HHT. Moreover, HHT underwent extensive metabolism; one major and two minor unidentified products were detected in both plasma and urine

  5. Late stillbirth post mortem examination in New Zealand: Maternal decision-making.

    Science.gov (United States)

    Cronin, Robin S; Li, Minglan; Wise, Michelle; Bradford, Billie; Culling, Vicki; Zuccollo, Jane; Thompson, John M D; Mitchell, Edwin A; McCowan, Lesley M E

    2018-03-05

    For parents who experience stillbirth, knowing the cause of their baby's death is important. A post mortem examination is the gold standard investigation, but little is known about what may influence parents' decisions to accept or decline. We aimed to identify factors influencing maternal decision-making about post mortem examination after late stillbirth. In the New Zealand Multicentre Stillbirth Study, 169 women with singleton pregnancies, no known abnormality at recruitment, and late stillbirth (≥28weeks gestation), from seven health regions were interviewed within six weeks of birth. The purpose of this paper was to explore factors related to post mortem examination decision-making and the reasons for declining. We asked women if they would make the same decision again. Maternal decision to decline a post mortem (70/169, 41.4%) was more common among women of Māori (adjusted odds ratio (aOR) 4.99 95% confidence interval (CI) 1.70-14.64) and Pacific (aOR 3.94 95% CI 1.47-10.54) ethnicity compared to European, and parity two or more (aOR 2.95 95% CI 1.14-7.62) compared to primiparous. The main reason for declining was that women 'did not want baby to be cut'. Ten percent (7/70) who declined said they would not make this decision again. No woman who consented regretted her decision. Ethnic differences observed in women's post mortem decision-making should be further explored in future studies. Providing information of the effect of post mortem on the baby's body and the possible emotional benefits of a post mortem may assist women faced with this decision in the future. © 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  6. Rigor mortis at the myocardium investigated by post-mortem magnetic resonance imaging.

    Science.gov (United States)

    Bonzon, Jérôme; Schön, Corinna A; Schwendener, Nicole; Zech, Wolf-Dieter; Kara, Levent; Persson, Anders; Jackowski, Christian

    2015-12-01

    Post-mortem cardiac MR exams present with different contraction appearances of the left ventricle in cardiac short axis images. It was hypothesized that the grade of post-mortem contraction may be related to the post-mortem interval (PMI) or cause of death and a phenomenon caused by internal rigor mortis that may give further insights in the circumstances of death. The cardiac contraction grade was investigated in 71 post-mortem cardiac MR exams (mean age at death 52 y, range 12-89 y; 48 males, 23 females). In cardiac short axis images the left ventricular lumen volume as well as the left ventricular myocardial volume were assessed by manual segmentation. The quotient of both (LVQ) represents the grade of myocardial contraction. LVQ was correlated to the PMI, sex, age, cardiac weight, body mass and height, cause of death and pericardial tamponade when present. In cardiac causes of death a separate correlation was investigated for acute myocardial infarction cases and arrhythmic deaths. LVQ values ranged from 1.99 (maximum dilatation) to 42.91 (maximum contraction) with a mean of 15.13. LVQ decreased slightly with increasing PMI, however without significant correlation. Pericardial tamponade positively correlated with higher LVQ values. Variables such as sex, age, body mass and height, cardiac weight and cause of death did not correlate with LVQ values. There was no difference in LVQ values for myocardial infarction without tamponade and arrhythmic deaths. Based on the observation in our investigated cases, the phenomenon of post-mortem myocardial contraction cannot be explained by the influence of the investigated variables, except for pericardial tamponade cases. Further research addressing post-mortem myocardial contraction has to focus on other, less obvious factors, which may influence the early post-mortem phase too. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Deuterium inventory in Tore Supra: reconciling particle balance and post-mortem analysis

    International Nuclear Information System (INIS)

    Tsitrone, E.; Brosset, C.; Pegourie, B.; Gauthier, E.; Bouvet, J.; Bucalossi, J.; Carpentier, S.; Corre, Y.; Delchambre, E.; Dittmar, T.; Douai, D.; Ekedahl, A.; Ghendrih, Ph.; Grisolia, C.; Grosman, A.; Gunn, J.; Hong, S.H.; Desgranges, L.; Escarguel, A.; Jacob, W.

    2009-01-01

    Fuel retention, a crucial issue for next step devices, is assessed in present-day tokamaks using two methods: particle balance performed during shots and post-mortem analysis carried out during shutdowns between experimental campaigns. Post-mortem analysis generally gives lower estimates of fuel retention than integrated particle balance. In order to understand the discrepancy between these two methods, a dedicated experimental campaign has been performed in Tore Supra to load the vessel walls with deuterium (D) and monitor the trapped D inventory through particle balance. The campaign was followed by an extensive post-mortem analysis phase of the Tore Supra limiter. This paper presents the status of the analysis phase, including the assessment of the D content in the castellated tile structure of the limiter. Indeed, using combined surface analysis techniques, it was possible to derive the relative contributions of different zones of interest on the limiter (erosion, thick deposits, thin deposits), showing that the post-mortem inventory is mainly due to codeposition (90% of the total), in particular due to gap deposits. However, deuterium was also evidenced deep into the material in erosion zones (10% of the total). At the present stage of the analysis, 50% of the inventory deduced from particle balance has been found through post-mortem analysis, a significant progress with respect to previous studies (factor 8-10 discrepancy). This shows that post-mortem analysis can be consistent with particle balance provided specific procedures are implemented (dedicated campaign followed by extensive post-mortem analysis). Both techniques are needed for a reliable assessment of fuel retention in tokamaks, giving complementary information on how much and where fuel is retained in the vessel walls.

  8. Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings.

    Science.gov (United States)

    Thom, Maria; Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W; Sisodiya, Sanjay M

    2016-08-01

    Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P detection of relevant pathology. Availability of full clinical epilepsy-related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. © 2015 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

  9. Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings

    Science.gov (United States)

    Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W.; Sisodiya, Sanjay M.

    2015-01-01

    Aims Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. Methods We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Results Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P epilepsy history and investigations. Conclusion Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy‐related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. PMID:26300477

  10. Post-mortem fetal MRI: What do we learn from it?

    International Nuclear Information System (INIS)

    Whitby, E.H.; Paley, M.N.J.; Cohen, M.; Griffiths, P.D.

    2006-01-01

    Post-mortem magnetic resonance (MR) imaging is of increasing interest not only as an alternative to autopsy but as a research tool to aid the interpretation and diagnosis of in utero MR images. The information from the post-mortem MR has allowed the development of imaging sequences applicable to in utero imaging and neonatal imaging. It has established brain development during gestation and has provided data on this to which in utero MR can be compared. The detail available from the post-mortem images is such that brain development can be studied in a non-invasive manner, a permanent record on the normal and abnormal areas is available and a greater understanding of developmental abnormalities is possible

  11. Value of systematic post mortem radiographic examinations of fetuses - 400 cases

    Energy Technology Data Exchange (ETDEWEB)

    Kalifa, G.; Sellier, N.; Barbet, J.P.; Labbe, F.; Houette, A.

    1989-01-01

    A retrospective study of 400 cases of fetal deaths has been carried out to assess the value of systematic post mortem radiological examination. Apart from general diagnosis purpose, special attention was given to the assessment of bone age and mineralization. The results were correlated with the clinical, U.S., chromosomal and pathological data. Computerized analysis of our information show the following results: (1) The radiological examination was valuable for the final diagnosis in 13.5% of cases. (2) It brings additional information in 34.5% of cases. (3) It had no diagnostic value in 52%. Furthermore several points deserve attention such as apparition of teeth (21 weeks), calcaneum (24 weeks). Major osteoporosis was always associated with a constitutional bone disease or an infectious process. An excessive length of the upper limbs (12) was seen in 11 cases of anencephaly. We suggest that a radiological examination should not be routinely performed, when the diagnosis is otherwise obvious, but should be considered in the presence of dwarfism, or other limb abnormalities and when the gestational age is uncertain. The films provide essential information especially for further genetic counselling.

  12. Value of systematic post mortem radiographic examinations of fetuses - 400 cases

    International Nuclear Information System (INIS)

    Kalifa, G.; Sellier, N.; Barbet, J.P.; Labbe, F.; Houette, A.

    1989-01-01

    A retrospective study of 400 cases of fetal deaths has been carried out to assess the value of systematic post mortem radiological examination. Apart from general diagnosis purpose, special attention was given to the assessment of bone age and mineralization. The results were correlated with the clinical, U.S., chromosomal and pathological data. Computerized analysis of our information show the following results: (1) The radiological examination was valuable for the final diagnosis in 13.5% of cases. (2) It brings additional information in 34.5% of cases. (3) It had no diagnostic value in 52%. Furthermore several points deserve attention such as apparition of teeth (21 weeks), calcaneum (24 weeks). Major osteoporosis was always associated with a constitutional bone disease or an infectious process. An excessive length of the upper limbs (12) was seen in 11 cases of anencephaly. We suggest that a radiological examination should not be routinely performed, when the diagnosis is otherwise obvious, but should be considered in the presence of dwarfism, or other limb abnormalities and when the gestational age is uncertain. The films provide essential information especially for further genetic counselling. (orig./MG)

  13. Characterisation of the metabolome of ocular tissues and post-mortem changes in the rat retina.

    Science.gov (United States)

    Tan, Shi Z; Mullard, Graham; Hollywood, Katherine A; Dunn, Warwick B; Bishop, Paul N

    2016-08-01

    Time-dependent post-mortem biochemical changes have been demonstrated in donor cornea and vitreous, but there have been no published studies to date that objectively measure post-mortem changes in the retinal metabolome over time. The aim of the study was firstly, to investigate post-mortem, time-dependent changes in the rat retinal metabolome and secondly, to compare the metabolite composition of healthy rat ocular tissues. To study post-mortem changes in the rat retinal metabolome, globes were enucleated and stored at 4 °C and sampled at 0, 2, 4, 8, 24 and 48 h post-mortem. To study the metabolite composition of rat ocular tissues, eyes were dissected immediately after culling to isolate the cornea, lens, vitreous and retina, prior to storing at -80 °C. Tissue extracts were subjected to Gas Chromatograph Mass Spectrometry (GC-MS) and Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS). Generally, the metabolic composition of the retina was stable for 8 h post-mortem when eyes were stored at 4 °C, but showed increasing changes thereafter. However, some more rapid changes were observed such as increases in TCA cycle metabolites after 2 h post-mortem, whereas some metabolites such as fatty acids only showed decreases in concentration from 24 h. A total of 42 metabolites were identified across the ocular tissues by GC-MS (MSI level 1) and 2782 metabolites were annotated by UHPLC-MS (MSI level 2) according to MSI reporting standards. Many of the metabolites detected were common to all of the tissues but some metabolites showed partitioning between different ocular structures with 655, 297, 93 and 13 metabolites being uniquely detected in the retina, lens, cornea and vitreous respectively. Only a small percentage (1.6%) of metabolites found in the vitreous were only detected in the retina and not other tissues. In conclusion, mass spectrometry-based techniques have been used for the first time to compare the metabolic composition of

  14. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

  15. Post-mortem cardiac diffusion tensor imaging: detection of myocardial infarction and remodeling of myofiber architecture.

    Science.gov (United States)

    Winklhofer, Sebastian; Stoeck, Christian T; Berger, Nicole; Thali, Michael; Manka, Robert; Kozerke, Sebastian; Alkadhi, Hatem; Stolzmann, Paul

    2014-11-01

    To investigate the accuracy of post-mortem diffusion tensor imaging (DTI) for the detection of myocardial infarction (MI) and to demonstrate the feasibility of helix angle (HA) calculation to study remodelling of myofibre architecture. Cardiac DTI was performed in 26 deceased subjects prior to autopsy for medicolegal reasons. Fractional anisotropy (FA) and mean diffusivity (MD) were determined. Accuracy was calculated on per-segment (AHA classification), per-territory, and per-patient basis, with pathology as reference standard. HAs were calculated and compared between healthy segments and those with MI. Autopsy demonstrated MI in 61/440 segments (13.9 %) in 12/26 deceased subjects. Healthy myocardial segments had significantly higher FA (p Analysis of HA distribution demonstrated remodelling of myofibre architecture, with significant differences between healthy segments and segments with chronic (p  0.05). Post-mortem cardiac DTI enables differentiation between healthy and infarcted myocardial segments by means of FA and MD. HA assessment allows for the demonstration of remodelling of myofibre architecture following chronic MI. • DTI enables post-mortem detection of myocardial infarction with good accuracy. • A decrease in right-handed helical fibre indicates myofibre remodelling following chronic myocardial infarction. • DTI allows for ruling out myocardial infarction by means of FA. • Post-mortem DTI may represent a valuable screening tool in forensic investigations.

  16. Experience with post-mortem computed tomography in Southern Denmark 2006-11

    DEFF Research Database (Denmark)

    Leth, Peter Mygind

    2013-01-01

    Objectives: (1) To explore the ability of post-mortem computed tomography (PMCT) to establish the cause of death. (2) To investigate the inter-method variation between autopsy and PMCT. (3) To investigate whether PMCT can select cases for autopsy. (4) To investigate the importance of histology...

  17. Routine perinatal and paediatric post-mortem radiography: detection rates and implications for practice

    Energy Technology Data Exchange (ETDEWEB)

    Arthurs, Owen J. [NHS Foundation Trust, Department of Radiology Great Ormond Street Hospital for Children, London (United Kingdom); University College London, Institute of Child Health, London (United Kingdom); Calder, Alistair D. [NHS Foundation Trust, Department of Radiology Great Ormond Street Hospital for Children, London (United Kingdom); Kiho, Liina [Camelia Botnar Laboratories Great Ormond Street Hospital for Children, Department of Paediatric Pathology, London (United Kingdom); Taylor, Andrew M. [Great Ormond Street Hospital for Children, Cardiorespiratory Unit, London (United Kingdom); UCL Institute of Cardiovascular Science, London (United Kingdom); University College London, Institute of Child Health, London (United Kingdom); Sebire, Neil J. [Camelia Botnar Laboratories Great Ormond Street Hospital for Children, Department of Paediatric Pathology, London (United Kingdom); University College London, Institute of Child Health, London (United Kingdom)

    2014-03-15

    Routine perinatal and paediatric post-mortem plain radiography allows for the diagnosis and assessment of skeletal dysplasias, fractures and other bony abnormalities. The aim of this study was to review the diagnostic yield of this practice. We identified 1,027 cases performed in a single institution over a 21/2-year period, including babygrams (whole-body examinations) and full skeletal surveys. Images were reported prior to autopsy in all cases. Radiology findings were cross-referenced with the autopsy findings using an autopsy database. We scored each case from 0 to 4 according to the level of diagnostic usefulness. The overall abnormality rate was 126/1,027 (12.3%). There was a significantly higher rate of abnormality when a skeletal survey was performed (18%) rather than a babygram (10%; P < 0.01); 90% (665/739) of babygrams were normal. Of the 74 abnormal babygrams, we found 33 incidental non-contributory cases, 19 contributory, 20 diagnostic, and 2 false-positive cases. There were only 2 cases out of 739 (0.27%) in whom routine post-mortem imaging identified potentially significant abnormalities that would not have been detected if only selected imaging had been performed. A policy of performing selected, rather than routine, foetal post-mortem radiography could result in a significant cost saving. Routine post-mortem paediatric radiography in foetuses and neonates is neither diagnostically useful nor cost-effective. A more evidence-based, selective protocol should yield significant cost savings. (orig.)

  18. Routine perinatal and paediatric post-mortem radiography: detection rates and implications for practice

    International Nuclear Information System (INIS)

    Arthurs, Owen J.; Calder, Alistair D.; Kiho, Liina; Taylor, Andrew M.; Sebire, Neil J.

    2014-01-01

    Routine perinatal and paediatric post-mortem plain radiography allows for the diagnosis and assessment of skeletal dysplasias, fractures and other bony abnormalities. The aim of this study was to review the diagnostic yield of this practice. We identified 1,027 cases performed in a single institution over a 21/2-year period, including babygrams (whole-body examinations) and full skeletal surveys. Images were reported prior to autopsy in all cases. Radiology findings were cross-referenced with the autopsy findings using an autopsy database. We scored each case from 0 to 4 according to the level of diagnostic usefulness. The overall abnormality rate was 126/1,027 (12.3%). There was a significantly higher rate of abnormality when a skeletal survey was performed (18%) rather than a babygram (10%; P < 0.01); 90% (665/739) of babygrams were normal. Of the 74 abnormal babygrams, we found 33 incidental non-contributory cases, 19 contributory, 20 diagnostic, and 2 false-positive cases. There were only 2 cases out of 739 (0.27%) in whom routine post-mortem imaging identified potentially significant abnormalities that would not have been detected if only selected imaging had been performed. A policy of performing selected, rather than routine, foetal post-mortem radiography could result in a significant cost saving. Routine post-mortem paediatric radiography in foetuses and neonates is neither diagnostically useful nor cost-effective. A more evidence-based, selective protocol should yield significant cost savings. (orig.)

  19. Post-mortem whole-body magnetic resonance imaging of human fetuses: a comparison of 3-T vs. 1.5-T MR imaging with classical autopsy.

    Science.gov (United States)

    Kang, Xin; Cannie, Mieke M; Arthurs, Owen J; Segers, Valerie; Fourneau, Catherine; Bevilacqua, Elisa; Cos Sanchez, Teresa; Sebire, Neil J; Jani, Jacques C

    2017-08-01

    To prospectively compare diagnostic accuracy of fetal post-mortem whole-body MRI at 3-T vs. 1.5-T. Between 2012 and 2015, post-mortem MRI at 1.5-T and 3-T was performed in fetuses after miscarriage/stillbirth or termination. Clinical MRI diagnoses were assessed using a confidence diagnostic score and compared with classical autopsy to derive a diagnostic error score. The relation of diagnostic error for each organ group with gestational age was calculated and 1.5-T with 3-T was compared with accuracy analysis. 135 fetuses at 12-41 weeks underwent post-mortem MRI (followed by conventional autopsy in 92 fetuses). For all organ groups except the brain, and for both modalities, the diagnostic error decreased with gestation (P autopsy than 1.5-T MRI, especially for the thorax, heart and abdomen in fetuses autopsy increases with 3-T. • PM-MRI using 3-T is particularly interesting for thoracic and abdominal organs. • PM-MRI using 3-T is particularly interesting for fetuses < 20 weeks' gestation.

  20. Diagnostic accuracy of post mortem MRI for abdominal abnormalities in foetuses and children

    International Nuclear Information System (INIS)

    Arthurs, Owen J.; Thayyil, Sudhin; Owens, Catherine M.; Olsen, Oystein E.; Wade, Angie; Addison, Shea; Jones, Rod; Norman, Wendy; Scott, Rosemary J.

    2015-01-01

    Highlights: •Postmortem MR imaging (PMMR) has high overall accuracy for abdominal pathology in foetuses, newborns and children. •PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. •In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities. -- Abstract: Background: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for abdominal pathology in foetuses and children, compared to conventional autopsy. Methods: Institutional ethics approval and parental consent was obtained. 400 unselected foetuses and children underwent PMMR using a 1.5 T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data respectively. Results: Abdominal abnormalities were found in 70/400 (12%) autopsies. Overall sensitivity and specificity (95% confidence interval) of PMMR for abdominal pathology was 72.5% (61.0, 81.6) and 90.8% (87.0, 93.6), with positive (PPV) and negative predictive values (NPV) of 64.1% (53.0, 73.9) and 93.6% (90.2, 95.8) respectively. PMMR was good at detecting renal abnormalities (sensitivity 80%), particularly in foetuses, and relatively poor at detecting intestinal abnormalities (sensitivity 50%). Overall accuracy was 87.4% (83.6, 90.4). Conclusions: PMMR has high overall accuracy for abdominal pathology in foetuses, newborns and children. PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities

  1. Diagnostic accuracy of post mortem MRI for abdominal abnormalities in foetuses and children

    Energy Technology Data Exchange (ETDEWEB)

    Arthurs, Owen J., E-mail: owen.arthurs@gosh.nhs.uk [Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Institute of Child Health, UCL, London (United Kingdom); Thayyil, Sudhin, E-mail: s.thayyil@imperial.ac.uk [Perinatal Neurology and Neonatology, Imperial College London, London (United Kingdom); Owens, Catherine M., E-mail: Catherine.owens@gosh.nhs.uk [Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London (United Kingdom); Cardiorespiratory Division, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Olsen, Oystein E., E-mail: oystein.olsen@gosh.nhs.uk [Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Institute of Child Health, UCL, London (United Kingdom); Wade, Angie, E-mail: a.wade@ucl.ac.uk [Clinical Epidemiology, Nutrition and Biostatistics Section, UCL Institute of Child health, London (United Kingdom); Addison, Shea, E-mail: shea.addison@imperial.ac.uk [Perinatal Neurology and Neonatology, Imperial College London, London (United Kingdom); Jones, Rod, E-mail: rod.jones@gosh.nhs.uk [Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London (United Kingdom); Cardiorespiratory Division, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Norman, Wendy, E-mail: wendy.norman@gosh.nhs.uk [Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London (United Kingdom); Cardiorespiratory Division, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Scott, Rosemary J., E-mail: rosemary.scott@uclh.nhs.uk [Department of Histopathology, University College London Hospital NHS Trust, London (United Kingdom); and others

    2015-03-15

    Highlights: •Postmortem MR imaging (PMMR) has high overall accuracy for abdominal pathology in foetuses, newborns and children. •PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. •In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities. -- Abstract: Background: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for abdominal pathology in foetuses and children, compared to conventional autopsy. Methods: Institutional ethics approval and parental consent was obtained. 400 unselected foetuses and children underwent PMMR using a 1.5 T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data respectively. Results: Abdominal abnormalities were found in 70/400 (12%) autopsies. Overall sensitivity and specificity (95% confidence interval) of PMMR for abdominal pathology was 72.5% (61.0, 81.6) and 90.8% (87.0, 93.6), with positive (PPV) and negative predictive values (NPV) of 64.1% (53.0, 73.9) and 93.6% (90.2, 95.8) respectively. PMMR was good at detecting renal abnormalities (sensitivity 80%), particularly in foetuses, and relatively poor at detecting intestinal abnormalities (sensitivity 50%). Overall accuracy was 87.4% (83.6, 90.4). Conclusions: PMMR has high overall accuracy for abdominal pathology in foetuses, newborns and children. PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities.

  2. Establishing post mortem criteria for the metabolic syndrome: an autopsy based cross-sectional study.

    Science.gov (United States)

    Christensen, Martin Roest; Bugge, Anne; Malik, Mariam Elmegaard; Thomsen, Jørgen Lange; Lynnerup, Niels; Rungby, Jørgen; Banner, Jytte

    2018-01-01

    Individuals who suffer from mental illness are more prone to obesity and related co-morbidities, including the metabolic syndrome. Autopsies provide an outstanding platform for the macroscopic, microscopic and molecular-biological investigation of diseases. Autopsy-based findings may assist in the investigation of the metabolic syndrome. To utilise the vast information that an autopsy encompasses to elucidate the pathophysiology behind the syndrome further, we aimed to both develop and evaluate a method for the post mortem definition of the metabolic syndrome. Based on the nationwide Danish SURVIVE study of deceased mentally ill, we established a set of post mortem criteria for each of the harmonized criteria of the metabolic syndrome. We based the post mortem (PM) evaluation on information from the police reports and the data collected at autopsy, such as anthropometric measurements and biochemical and toxicological analyses (PM information). We compared our PM evaluation with the data from the Danish health registries [ante mortem (AM) information, considered the gold standard] from each individual. The study included 443 deceased individuals (272 male and 171 female) with a mean age of 50.4 (± 15.5) years and a median (interquartile range) post mortem interval of 114 (84-156) hours. We found no significant difference when defining the metabolic syndrome from the PM information in comparison to the AM information ( P  = 0.175). The PM evaluation yielded a high specificity (0.93) and a moderate sensitivity (0.63) with a moderate level of agreement compared to the AM evaluation (Cohen's κ = 0.51). Neither age nor post mortem interval affected the final results. Our model of a PM definition of the metabolic syndrome proved reliable when compared to the AM information. We believe that an appropriate estimate of the prevalence of the metabolic syndrome can be established post mortem. However, while neither the PM nor the AM information is exhaustive in

  3. Pharmacology Portal: An Open Database for Clinical Pharmacologic Laboratory Services.

    Science.gov (United States)

    Karlsen Bjånes, Tormod; Mjåset Hjertø, Espen; Lønne, Lars; Aronsen, Lena; Andsnes Berg, Jon; Bergan, Stein; Otto Berg-Hansen, Grim; Bernard, Jean-Paul; Larsen Burns, Margrete; Toralf Fosen, Jan; Frost, Joachim; Hilberg, Thor; Krabseth, Hege-Merete; Kvan, Elena; Narum, Sigrid; Austgulen Westin, Andreas

    2016-01-01

    More than 50 Norwegian public and private laboratories provide one or more analyses for therapeutic drug monitoring or testing for drugs of abuse. Practices differ among laboratories, and analytical repertoires can change rapidly as new substances become available for analysis. The Pharmacology Portal was developed to provide an overview of these activities and to standardize the practices and terminology among laboratories. The Pharmacology Portal is a modern dynamic web database comprising all available analyses within therapeutic drug monitoring and testing for drugs of abuse in Norway. Content can be retrieved by using the search engine or by scrolling through substance lists. The core content is a substance registry updated by a national editorial board of experts within the field of clinical pharmacology. This ensures quality and consistency regarding substance terminologies and classification. All laboratories publish their own repertoires in a user-friendly workflow, adding laboratory-specific details to the core information in the substance registry. The user management system ensures that laboratories are restricted from editing content in the database core or in repertoires within other laboratory subpages. The portal is for nonprofit use, and has been fully funded by the Norwegian Medical Association, the Norwegian Society of Clinical Pharmacology, and the 8 largest pharmacologic institutions in Norway. The database server runs an open-source content management system that ensures flexibility with respect to further development projects, including the potential expansion of the Pharmacology Portal to other countries. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  4. Partitioning the proteome: phase separation for targeted analysis of membrane proteins in human post-mortem brain.

    Directory of Open Access Journals (Sweden)

    Jane A English

    Full Text Available Neuroproteomics is a powerful platform for targeted and hypothesis driven research, providing comprehensive insights into cellular and sub-cellular disease states, Gene × Environmental effects, and cellular response to medication effects in human, animal, and cell culture models. Analysis of sub-proteomes is becoming increasingly important in clinical proteomics, enriching for otherwise undetectable proteins that are possible markers for disease. Membrane proteins are one such sub-proteome class that merit in-depth targeted analysis, particularly in psychiatric disorders. As membrane proteins are notoriously difficult to analyse using traditional proteomics methods, we evaluate a paradigm to enrich for and study membrane proteins from human post-mortem brain tissue. This is the first study to extensively characterise the integral trans-membrane spanning proteins present in human brain. Using Triton X-114 phase separation and LC-MS/MS analysis, we enriched for and identified 494 membrane proteins, with 194 trans-membrane helices present, ranging from 1 to 21 helices per protein. Isolated proteins included glutamate receptors, G proteins, voltage gated and calcium channels, synaptic proteins, and myelin proteins, all of which warrant quantitative proteomic investigation in psychiatric and neurological disorders. Overall, our sub-proteome analysis reduced sample complexity and enriched for integral membrane proteins by 2.3 fold, thus allowing for more manageable, reproducible, and targeted proteomics in case vs. control biomarker studies. This study provides a valuable reference for future neuroproteomic investigations of membrane proteins, and validates the use Triton X-114 detergent phase extraction on human post mortem brain.

  5. Effect of gamma irradiation on the microstructure and post-mortem anaerobic metabolism of bovine muscle

    International Nuclear Information System (INIS)

    Yook, H.-S.; Lee, J.-W.; Lee, K.-H.; Kim, M.-K.; Song, C.-W.; Byun, M.-W.

    2001-01-01

    Experiments were performed to study the effect of gamma irradiation on morphological properties and post-mortem metabolism in bovine M. sternomandibularis with special reference to ultrastructure, shear force, pH and ATP breakdown. The shortening of sarcomere was not observed in gamma-irradiated muscle, however, the disappearance of M-line and of A- and I-bands was perceptible. During cold storage, the destruction of muscle bundles was faster in the gamma-irradiated muscle than in the non-irradiated with a dose-dependent manner. The same is true for the post mortem pH drop and ATP breakdown. So, experimental results confirmed that the anaerobic metabolism and morphological properties are noticeably affected by gamma irradiation in beef

  6. Diagnosis of drowning using post-mortem computed tomography - state of the art.

    Science.gov (United States)

    Raux, C; Saval, F; Rouge, D; Telmon, N; Dedouit, F

    Recent studies using post-mortem computed tomography (PMCT) have suggested this imaging modality is of value in the positive diagnosis of drowning. We summarize the data from the literature regarding the diagnostic value of CT in cases of drowning. We performed an all-language search of literature published from 1999 to 2013 with the key words "post-mortem CT scan", "drowning and CT scan", "near-drowning diagnosis", and "drowning diagnosis". Only 11 articles, whose data enabled complementary statistical analysis, were included. The presence of fluid and sediment in paranasal sinuses appear to be the determinants of the diagnosis of drowning. The presence of fluid in the sinuses had a sensitivity of 100%, and of 90% in the trachea and main bronchi. The results were completed by the high specificity of the presence of sediment in the paranasal sinuses, upper airways and stomach, which was 100% for all three. Haemodilution was present in cases of drowning (p drowning.

  7. Post-mortem cardiac diffusion tensor imaging: detection of myocardial infarction and remodeling of myofiber architecture

    International Nuclear Information System (INIS)

    Winklhofer, Sebastian; Berger, Nicole; Stolzmann, Paul; Stoeck, Christian T.; Kozerke, Sebastian; Thali, Michael; Manka, Robert; Alkadhi, Hatem

    2014-01-01

    To investigate the accuracy of post-mortem diffusion tensor imaging (DTI) for the detection of myocardial infarction (MI) and to demonstrate the feasibility of helix angle (HA) calculation to study remodelling of myofibre architecture. Cardiac DTI was performed in 26 deceased subjects prior to autopsy for medicolegal reasons. Fractional anisotropy (FA) and mean diffusivity (MD) were determined. Accuracy was calculated on per-segment (AHA classification), per-territory, and per-patient basis, with pathology as reference standard. HAs were calculated and compared between healthy segments and those with MI. Autopsy demonstrated MI in 61/440 segments (13.9 %) in 12/26 deceased subjects. Healthy myocardial segments had significantly higher FA (p 0.05). Post-mortem cardiac DTI enablesdifferentiation between healthy and infarcted myocardial segments by means of FA and MD. HA assessment allows for the demonstration of remodelling of myofibre architecture following chronic MI. (orig.)

  8. Various methods for the estimation of the post mortem interval from Calliphoridae: A review

    Directory of Open Access Journals (Sweden)

    Ruchi Sharma

    2015-03-01

    Forensic entomology is recognized in many countries as an important tool for legal investigations. Unfortunately, it has not received much attention in India as an important investigative tool. The maggots of the flies crawling on the dead bodies are widely considered to be just another disgusting element of decay and are not collected at the time of autopsy. They can aid in death investigations (time since death, manner of death, etc.. This paper reviews the various methods of post mortem interval estimation using Calliphoridae to make the investigators, law personnel and researchers aware of the importance of entomology in criminal investigations. The various problems confronted by forensic entomologists in estimating the time since death have also been discussed and there is a need for further research in the field as well as the laborator. Correct estimation of the post mortem interval is one of the most important aspects of legal medicine.

  9. Viability and infectivity of Ichthyophonus sp. in post-mortem Pacific herring, Clupea pallasii.

    Science.gov (United States)

    Kocan, Richard; Hart, Lucas; Lewandowski, Naomi; Hershberger, Paul

    2014-12-01

    Ichthyophonus-infected Pacific herring, Clupea pallasii , were allowed to decompose in ambient seawater then serially sampled for 29 days to evaluate parasite viability and infectivity for Pacific staghorn sculpin, Leptocottus armatus . Ichthyophonus sp. was viable in decomposing herring tissues for at least 29 days post-mortem and could be transmitted via ingestion to sculpin for up to 5 days. The parasite underwent morphologic changes during the first 48 hr following death of the host that were similar to those previously reported, but as host tissue decomposition progressed, several previously un-described forms of the parasite were observed. The significance of long-term survival and continued morphologic transformation in the post-mortem host is unknown, but it could represent a saprozoic phase of the parasite life cycle that has survival value for Ichthyophonus sp.

  10. Diagnosis of porcine enzootic pneumonia by post mortem sanitary inspection: comparison with other diagnostic methods

    OpenAIRE

    Kênia de Fátima Carrijo; Elmiro Rosendo do Nascimento; Virginia Léo de Almeida Pereira; Nelson Morés; Catia Silene Klein; Leonardo Muliterno Domingues; Rogerio Tortelly

    2014-01-01

    ABSTRACT. Carrijo K.F., Nascimento E.R., Pereira V.L.A., Morés N., Klein, C.S., Domingues L.M. & Tortelly R. [Diagnosis of porcine enzootic pneumonia by post mortem sanitary inspection: comparison with other diagnostic methods.] Diagnóstico da pneumonia enzoótica suína pela inspeção sanitária post mortem: comparação com outros métodos de diagnóstico. Revista Brasileira de Veterinária Brasileira 36(2):188-194, 2014. Faculdade de Medicina Veterinária, Universidade Federal de Uberlândia, Av. Par...

  11. [Inheritance rights fo the child born from post-mortem fertilization].

    Science.gov (United States)

    Iniesta Delgado, Juan José

    2008-01-01

    Spanish Law allows in the possibility of post mortem fertilization, recognizing the paternity of the deceased male. The most prominent legal effects of this fact have to do with the succession of his father. The way of fixing the child's portion in the forced succession and its protection, the question of determining his share in the inheritance and the necessity of defending his rights until the verification of the birth are some of the issues that are discussed in this article.

  12. Post-mortem changes in the physical meat quality characteristics of ...

    African Journals Online (AJOL)

    ... apparatus) of the muscle generally improved with time. The quadratic equation y = -0.0817x2 + 0.4468x + 10.477 best described (R2 = 0.32) this improvement in tenderness. The implications of this result is that fresh game meat producers can de-bone carcasses after 24 hours post mortem and leave the primal cuts to age ...

  13. Forensic aspects of incised wounds and bruises in pigs established post-mortem

    DEFF Research Database (Denmark)

    Barington, Kristiane; Jensen, Henrik Elvang

    2017-01-01

    Recognizing post-mortem (PM) changes is of crucial importance in veterinary forensic pathology. In porcine wounds established PM contradicting observations regarding infiltration of leukocytes have been described. In the present study, skin, subcutis and muscle tissue sampled from experimental pigs...... of sampling. Moreover, it was found that AM bruises free of leukocyte infiltration cannot be distinguished from PM bruises, an observation which is of crucial importance when timing bruises in forensic cases....

  14. Uses and social meanings of post-mortem photography in Colombia

    OpenAIRE

    Ana María Henao Albarracín

    2013-01-01

    This research is intended to understand the social uses and meanings of post-mortem or funeral photography between the late nineteenth and mid-twentieth century in Colombia. The article seeks to contribute to the analysis of the relationship between photography and society, and more particularly, between photography and a social representation of death, identifying the conventions and rules of this photographic practice that determine aesthetic behaviors around death.

  15. DNA methylation results depend on DNA integrity – role of post mortem interval

    Directory of Open Access Journals (Sweden)

    Mathias eRhein

    2015-05-01

    Full Text Available Major questions of neurological and psychiatric mechanisms involve the brain functions on a molecular level and cannot be easily addressed due to limitations in access to tissue samples. Post mortem studies are able to partly bridge the gap between brain tissue research retrieved from animal trials and the information derived from peripheral analysis (e.g. measurements in blood cells in patients. Here, we wanted to know how fast DNA degradation is progressing under controlled conditions in order to define thresholds for tissue quality to be used in respective trials. Our focus was on the applicability of partly degraded samples for bisulfite sequencing and the determination of simple means to define cut-off values.After opening the brain cavity, we kept two consecutive pig skulls at ambient temperature (19-21°C and removed cortex tissue up to a post mortem interval (PMI of 120h. We calculated the percentage of degradation on DNA gel electrophoresis of brain DNA to estimate quality and relate this estimation spectrum to the quality of human post-mortem control samples. Functional DNA quality was investigated by bisulfite sequencing of two functionally relevant genes for either the serotonin receptor 5 (SLC6A4 or aldehyde dehydrogenase 2 (ALDH2.Testing our approach in a heterogeneous collective of human blood and brain samples, we demonstrate integrity of measurement quality below the threshold of 72h PMI.While sequencing technically worked for all timepoints irrespective of conceivable DNA degradation, there is a good correlation between variance of methylation to degradation levels documented in the gel (R2=0.4311, p=0.0392 for advancing post mortem intervals (PMI. This otherwise elusive phenomenon is an important prerequisite for the interpretation and evaluation of samples prior to in-depth processing via an affordable and easy assay to estimate identical sample quality and thereby comparable methylation measurements.

  16. Uses and social meanings of post-mortem photography in Colombia

    Directory of Open Access Journals (Sweden)

    Ana María Henao Albarracín

    2013-06-01

    Full Text Available This research is intended to understand the social uses and meanings of post-mortem or funeral photography between the late nineteenth and mid-twentieth century in Colombia. The article seeks to contribute to the analysis of the relationship between photography and society, and more particularly, between photography and a social representation of death, identifying the conventions and rules of this photographic practice that determine aesthetic behaviors around death.

  17. The use of contrast-enhanced post Mortem CT in the detection of cardiovascular deaths.

    Directory of Open Access Journals (Sweden)

    Jonas Christoph Apitzsch

    Full Text Available OBJECTIVES: To evaluate the diagnostic value of contrast enhanced post mortem computed tomography (PMCT in comparison to non-enhanced post mortem CT in the detection of cardiovascular causes of death (COD. BACKGROUND: As autopsy rates decline, new methods to determine CODs are necessary. So contrast enhanced PMCT shall be evaluated in comparison to established non-enhanced PMCT in order to further improve the method. METHODS: In a prospective study, 20 corpses were examined using a 64-row multisclice CT (MSCT before and after intraarterial perfusion with a newly developed, barium-bearing contrast agent and ventilation of the lungs. The cause of death was determined in enhanced and unenhanced scans and a level of confidence (LOC was given by three experienced radiologists on a scale between 0 and 4. Results were compared to autopsy results as gold standard. Autopsy was performed blinded to PMCT-findings. RESULTS: The method allowed visualization of different types of cause of death. There was a significant improvement in LOC in enhanced scans compared to unenhanced scans as well as an improvement in the detection of COD. The cause of death could be determined in 19 out of 20 patients. CONCLUSIONS: PMCT is feasible and appears to be robust for diagnosing cardiovascular causes of death. When compared with unenhanced post-mortem CT intraarterial perfusion and pulmonary ventilation significantly improve visualization and diagnostic accuracy. These promising results warrant further studies.

  18. A Case Study in Support of Multiple Post Mortem Assessments (Invited Paper

    Directory of Open Access Journals (Sweden)

    Jill Pable

    2015-02-01

    Full Text Available Creative projects in various fields are often subjected to afterthe- fact 'post-mortem' assessments to better understand their successes and failures. Names for these include project retrospectives or post occupancy evaluations (POEs depending on their field of origin. This case study from the architecture field will show the utility of engaging in multiple rounds of post-mortem activities in order to assess the solution from multiple stakeholder perspectives and in doing so, more fully recognize its strengths and weaknesses. The design of a homeless shelter bedroom was subjected to two POE analyses: a 'demand side' focused study that analyzed user accommodation, and a 'supply side' study that addressed issues including budget and funding. The two POEs yielded both corroborative and contrasting findings that sometimes worked at cross purposes. Three evaluation tactics emerged that could be extended to other fields' post mortem assessment activities: 1 conduct two or more POEs; 2 vary the POE criteria so that one is deep and focused 'demand side' user analysis and the other is 'supply side' operational and installation issues; and 3 conduct the POEs over a broad time period.

  19. Assessment of coronary artery disease by post-mortem cardiac MR

    International Nuclear Information System (INIS)

    Ruder, Thomas D.; Bauer-Kreutz, Regula; Ampanozi, Garyfalia; Rosskopf, Andrea B.; Pilgrim, Thomas M.; Weber, Oliver M.; Thali, Michael J.; Hatch, Gary M.

    2012-01-01

    Objectives: Minimally invasive or virtual autopsies are being advocated as alternative to traditional autopsy, but have limited abilities to detect coronary artery disease. It was the objective of this study to assess if the occurrence of chemical shift artifacts (CSA) along the coronary arteries on non-contrast, post-mortem cardiac MR may be used to investigate coronary artery disease. Methods: We retrospectively compared autopsy and CT findings of 30 cases with significant (≥75%), insignificant (<75%), or absent coronary artery stenosis to post-mortem cardiac MR findings. The chi-square test was used to investigate if the occurrence of CSA depends on the presence or absence of stenosis. Sensitivity, specificity and predictive values were calculated for each finding. Results: CSA indicates the absence of (significant) stenosis (p < 0.001). The occurrence of paired dark bands in lieu of CSA on post-mortem cardiac MR suggests (significant) coronary arteries stenosis (p < 0.001). Both findings have a high specificity but low sensitivity. Conclusions: CSA is a marker of vessel patency. The presence of paired dark bands indicates stenosis. These criteria improve the ability of minimally invasive or virtual autopsy to detect coronary artery disease related deaths

  20. Post-mortem cardiac diffusion tensor imaging: detection of myocardial infarction and remodeling of myofiber architecture

    Energy Technology Data Exchange (ETDEWEB)

    Winklhofer, Sebastian; Berger, Nicole; Stolzmann, Paul [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); Stoeck, Christian T.; Kozerke, Sebastian [Institute for Biomedical Engineering University and ETH Zurich, Zurich (Switzerland); Thali, Michael [University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); Manka, Robert [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Institute for Biomedical Engineering University and ETH Zurich, Zurich (Switzerland); University Hospital Zurich, Clinic for Cardiology, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2014-11-15

    To investigate the accuracy of post-mortem diffusion tensor imaging (DTI) for the detection of myocardial infarction (MI) and to demonstrate the feasibility of helix angle (HA) calculation to study remodelling of myofibre architecture. Cardiac DTI was performed in 26 deceased subjects prior to autopsy for medicolegal reasons. Fractional anisotropy (FA) and mean diffusivity (MD) were determined. Accuracy was calculated on per-segment (AHA classification), per-territory, and per-patient basis, with pathology as reference standard. HAs were calculated and compared between healthy segments and those with MI. Autopsy demonstrated MI in 61/440 segments (13.9 %) in 12/26 deceased subjects. Healthy myocardial segments had significantly higher FA (p < 0.01) and lower MD (p < 0.001) compared to segments with MI. Multivariate logistic regression demonstrated that FA (p < 0.10) and MD (p = 0.01) with the covariate post-mortem time (p < 0.01) predicted MI with an accuracy of 0.73. Analysis of HA distribution demonstrated remodelling of myofibre architecture, with significant differences between healthy segments and segments with chronic (p < 0.001) but not with acute MI (p > 0.05). Post-mortem cardiac DTI enablesdifferentiation between healthy and infarcted myocardial segments by means of FA and MD. HA assessment allows for the demonstration of remodelling of myofibre architecture following chronic MI. (orig.)

  1. Effects of post mortem interval and gender in DNA base excision repair activities in rat brains

    Energy Technology Data Exchange (ETDEWEB)

    Soltys, Daniela Tathiana; Pereira, Carolina Parga Martins; Ishibe, Gabriela Naomi; Souza-Pinto, Nadja Cristhina de, E-mail: nadja@iq.usp.br

    2015-06-15

    Most human tissues used in research are of post mortem origin. This is the case for all brain samples, and due to the difficulty in obtaining a good number of samples, especially in the case of neurodegenerative diseases, male and female samples are often included in the same experimental group. However, the effects of post mortem interval (PMI) and gender differences in the endpoints being analyzed are not always fully understood, as is the case for DNA repair activities. To investigate these effects, in a controlled genetic background, base excision repair (BER) activities were measured in protein extracts obtained from Wistar rat brains from different genders and defined PMI up to 24 hours, using a novel fluorescent-based in vitro incision assay. Uracil and AP-site incision activity in nuclear and mitochondrial extracts were similar in all groups included in this study. Our results show that gender and PMI up to 24 hours have no influence in the activities of the BER proteins UDG and APE1 in rat brains. These findings demonstrate that these variables do not interfere on the BER activities included in these study, and provide a security window to work with UDG and APE1 proteins in samples of post mortem origin.

  2. Effects of post mortem interval and gender in DNA base excision repair activities in rat brains

    International Nuclear Information System (INIS)

    Soltys, Daniela Tathiana; Pereira, Carolina Parga Martins; Ishibe, Gabriela Naomi; Souza-Pinto, Nadja Cristhina de

    2015-01-01

    Most human tissues used in research are of post mortem origin. This is the case for all brain samples, and due to the difficulty in obtaining a good number of samples, especially in the case of neurodegenerative diseases, male and female samples are often included in the same experimental group. However, the effects of post mortem interval (PMI) and gender differences in the endpoints being analyzed are not always fully understood, as is the case for DNA repair activities. To investigate these effects, in a controlled genetic background, base excision repair (BER) activities were measured in protein extracts obtained from Wistar rat brains from different genders and defined PMI up to 24 hours, using a novel fluorescent-based in vitro incision assay. Uracil and AP-site incision activity in nuclear and mitochondrial extracts were similar in all groups included in this study. Our results show that gender and PMI up to 24 hours have no influence in the activities of the BER proteins UDG and APE1 in rat brains. These findings demonstrate that these variables do not interfere on the BER activities included in these study, and provide a security window to work with UDG and APE1 proteins in samples of post mortem origin

  3. The Dutch vision of clinical pharmacology

    NARCIS (Netherlands)

    Schellens, J H M; Grouls, R; Guchelaar, H J; Touw, D J; Rongen, G A; de Boer, A; Van Bortel, L M

    Recent position papers addressing the profession of clinical pharmacology have expressed concerns about the decline of interest in the field among clinicians and medical educators in the United Kingdom and other Western countries, whether clinical pharmacology is actually therapeutics, and whether

  4. [Research Progress of Carrion-breeding Phorid Flies for Post-mortem Interval Estimation in Forensic Medicine].

    Science.gov (United States)

    Li, L; Feng, D X; Wu, J

    2016-10-01

    It is a difficult problem of forensic medicine to accurately estimate the post-mortem interval. Entomological approach has been regarded as an effective way to estimate the post-mortem interval. The developmental biology of carrion-breeding flies has an important position at the post-mortem interval estimation. Phorid flies are tiny and occur as the main or even the only insect evidence in relatively enclosed environments. This paper reviews the research progress of carrion-breeding phorid flies for estimating post-mortem interval in forensic medicine which includes their roles, species identification and age determination of immatures. Copyright© by the Editorial Department of Journal of Forensic Medicine.

  5. Bioanalysis, metabolism & clinical pharmacology of antiretroviral drugs

    NARCIS (Netherlands)

    Heine, R. ter

    2009-01-01

    The aims of all studies described in this thesis were to develop new bioanalytical and more patient friendly methods for studying the clinical pharmacology of antiretroviral drugs and to ultimately improve antiretroviral treatment.

  6. Post-mortem detection of gasoline residues in lung tissue and heart blood of fire victims.

    Science.gov (United States)

    Pahor, Kevin; Olson, Greg; Forbes, Shari L

    2013-09-01

    The purpose of this study was to determine whether gasoline residues could be detected post-mortem in lung tissue and heart blood of fire victims. The lungs and heart blood were investigated to determine whether they were suitable samples for collection and could be collected without contamination during an autopsy. Three sets of test subjects (pig carcasses) were investigated under two different fire scenarios. Test subjects 1 were anaesthetized following animal ethics approval, inhaled gasoline vapours for a short period and then euthanized. The carcasses were clothed and placed in a house where additional gasoline was poured onto the carcass post-mortem in one fire, but not in the other. Test subjects 2 did not inhale gasoline, were clothed and placed in the house and had gasoline poured onto them in both fires. Test subjects 3 were clothed but had no exposure to gasoline either ante- or post-mortem. Following controlled burns and suppression with water, the carcasses were collected, and their lungs and heart blood were excised at a necropsy. The headspace from the samples was analysed using thermal desorption-gas chromatography-mass spectroscopy. Gasoline was identified in the lungs and heart blood from the subjects that were exposed to gasoline vapours prior to death (test subjects 1). All other samples were negative for gasoline residues. These results suggest that it is useful to analyse for volatile ignitable liquids in lung tissue and blood as it may help to determine whether a victim was alive and inhaling gases at the time of a fire.

  7. Characteristics of human infant primary fibroblast cultures from Achilles tendons removed post-mortem

    DEFF Research Database (Denmark)

    Rohde, Marianne Cathrine; Corydon, Thomas Juhl; Hansen, Jakob

    2014-01-01

    Primary cell cultures were investigated as a tool for molecular diagnostics in a forensic setting. Fibroblast cultures had been established from human Achilles tendon resected at autopsies, from cases of sudden infant death syndrome and control infants who died in traumatic events (n=41). After...... established from post-mortem tissue are renewable sources of biological material; they can be the foundation for genetic, metabolic and other functional studies and thus constitute a valuable tool for molecular and pathophysiological investigations in biomedical and forensic sciences....

  8. Microstructural analysis of geopolymer developed from wood fly ash, post-mortem doloma refractory and metakaolin

    International Nuclear Information System (INIS)

    Moura, Jailes de Santana; Mafra, Marcio Paulo de Araujo; Rabelo, Adriano Alves; Fagury, Renata Lilian Ribeiro Portugal; Fagury Neto, Elias

    2016-01-01

    Geopolymers are one of the widely discussed topics of materials science in recent times due to its vast potential as an alternative binder material to cement. This work aimed to evaluate the microstructure of geopolymers developed from wood fly ash, post-mortem doloma refractory and metakaolin. A preliminary study has been completed and achieved significant results compressive strength: the best formulation of geopolymer paste obtained approximately 25 MPa. Microstructural analysis by scanning electron microscopy, the geopolymer paste, allowed to verify the homogeneity, distribution of components, and providing evidence of raw materials that do not respond if there was crystalline phase, porosity and density of the structure. (author)

  9. Increased concentration of. cap alpha. - and. gamma. -endorphin in post mortem hypothalamic tissue of schizophrenic patients

    Energy Technology Data Exchange (ETDEWEB)

    Wiegant, V.M.; Verhoef, C.J.; Burbach, J.P.H.; de Wied, D.

    1988-01-01

    The concentrations of ..cap alpha..-, ..beta..- and ..gamma..-endorphin were determined by radioimmunoassay in HPLC fractionated extracts of post mortem hypothalamic tissue obtained from schizophrenic patients and controls. The hypothalamic concentration of ..cap alpha..- and ..gamma..-endorphin was significantly higher in patients than in controls. No difference was found in the concentration of ..beta..-endorphin, the putative precursor of ..cap alpha..- and ..gamma..-endorphins. These results suggest a deviant metabolism of ..beta..-endorphin in the brain of schizophrenic patients. Whether this phenomenon is related to the psychopathology, or is a consequence of ante mortem farmacotherapy, remains to be established.

  10. Intravital and post-mortem CT examinations of cerebral gunshot injuries

    International Nuclear Information System (INIS)

    Schumacher, M.; Oehmichen, M.; Koenig, H.G.; Einighammer, H.; Koeln Univ.; Tuebingen Univ.; Duesseldorf Univ.

    1983-01-01

    The value of CT was assessed in 24 patients who died of cerebral gun-shot injuries and in two patients with more recent injuries in order to reconstruct the mode of injury and for adding forensic information. The post-mortem and intravital appearances are described and are compared with ultrasound rotation compound scans of the isolated brains. CT showed good agreement with pathological findings. Ultrasound produced images with an accuracy between CT and photographs of the brain specimen. Both methods are regarded as valuable additions to the pathological and forensic information concerning gunshot injuries. (orig.) [de

  11. Usos y significados sociales de la fotografía post-mortem en Colombia

    OpenAIRE

    Henao Albarracín, Ana María; Universidad Paris Ouest Nanterre La Défense, Paris, Francia

    2013-01-01

    Esta investigación tiene como finalidad conocer los usos y significados sociales de la fotografía post-mortem o fúnebre entre finales del XIX y mediados del siglo XX en Colombia. De tal forma, busca contribuir al análisis de las relaciones entre fotografía y sociedad, y más particularmente, entre la fotografía y una representación social de la muerte, identificando las convenciones y reglas de esta práctica fotográfica que determinan comportamientos estéticos alrededor de la muerte. This r...

  12. Post-mortem re-cloning of a transgenic red fluorescent protein dog.

    Science.gov (United States)

    Hong, So Gun; Koo, Ok Jae; Oh, Hyun Ju; Park, Jung Eun; Kim, Minjung; Kim, Geon-A; Park, Eun Jung; Jang, Goo; Lee, Byeong-Chun

    2011-12-01

    Recently, the world's first transgenic dogs were produced by somatic cell nuclear transfer. However, cellular senescence is a major limiting factor for producing more advanced transgenic dogs. To overcome this obstacle, we rejuvenated transgenic cells using a re-cloning technique. Fibroblasts from post-mortem red fluorescent protein (RFP) dog were reconstructed with in vivo matured oocytes and transferred into 10 surrogate dogs. One puppy was produced and confirmed as a re-cloned dog. Although the puppy was lost during birth, we successfully established a rejuvenated fibroblast cell line from this animal. The cell line was found to stably express RFP and is ready for additional genetic modification.

  13. Post-mortem 3H-thymidine incorporation in human epidermis and oral mucosa

    International Nuclear Information System (INIS)

    Schellmann, B.

    1981-01-01

    Using the 3H-thymidine labelling method, the authors studied post-mortem incorporation activity in the epidermis and oral mucosa of corpses which were stored with their clothes on under conditions of normal room temperature (+20 0 ) and of cooling (+4 0 C). Samples were taken in the form of skin punches at 2 h or 4 h intervals, respec.. Using histo-autoradiograms, the incorporation of 3H-thymidine in dependence from the time interval between the points of time of death and sampling were determined in situe and given as the ratio of labelled cells of the germinative layer per 100 μm length of basement membrane. A linear drop of post-mortem thymidine incorporation rates in epidermis and oral mucosa was found in human corpse skin correlating with increasing temporal distance from the point of time of death. Incorporation rates in the oral mucosa were markedly higher (by a factor of 3 to 5) than those of the epidermis which agrees well with in vivo conditions. No labelling of cell nuclei, i.e. no synthetic activity of the germinative layer, could be detected in the epidermis 35-40 h after individual death at the latest (in the oral mucosa after 45-50 h). However, clear incorporation activities could be observed in the germinative layer of epidermis and oral mucosa after more than 4 d in the case of storage at +4 0 C. (orig./MG) [de

  14. Diagnosis of drowning using post-mortem computed tomography – state of the art

    Directory of Open Access Journals (Sweden)

    Catherine Raux

    2014-12-01

    Full Text Available Aim of the study: Recent studies using post-mortem computed tomography (PMCT have suggested this imaging modality is of value in the positive diagnosis of drowning. We summarize the data from the literature regarding the diagnostic value of CT in cases of drowning. Material and methods: We performed an all-language search of literature published from 1999 to 2013 with the key words “post-mortem CT scan”, “drowning and CT scan”, “near-drowning diagnosis”, and “drowning diagnosis”. Results : Only 11 articles, whose data enabled complementary statistical analysis, were included. The presence of fluid and sediment in paranasal sinuses appear to be the determinants of the diagnosis of drowning. The presence of fluid in the sinuses had a sensitivity of 100%, and of 90% in the trachea and main bronchi. The results were completed by the high specificity of the presence of sediment in the paranasal sinuses, upper airways and stomach, which was 100% for all three. Haemodilution was present in cases of drowning (p < 0.001. The values made it possible to formulate a decision algorithm for the diagnosis of drowning.

  15. Profiling of RNA degradation for estimation of post mortem [corrected] interval.

    Directory of Open Access Journals (Sweden)

    Fernanda Sampaio-Silva

    Full Text Available An estimation of the post mortem interval (PMI is frequently touted as the Holy Grail of forensic pathology. During the first hours after death, PMI estimation is dependent on the rate of physical observable modifications including algor, rigor and livor mortis. However, these assessment methods are still largely unreliable and inaccurate. Alternatively, RNA has been put forward as a valuable tool in forensic pathology, namely to identify body fluids, estimate the age of biological stains and to study the mechanism of death. Nevertheless, the attempts to find correlation between RNA degradation and PMI have been unsuccessful. The aim of this study was to characterize the RNA degradation in different post mortem tissues in order to develop a mathematical model that can be used as coadjuvant method for a more accurate PMI determination. For this purpose, we performed an eleven-hour kinetic analysis of total extracted RNA from murine's visceral and muscle tissues. The degradation profile of total RNA and the expression levels of several reference genes were analyzed by quantitative real-time PCR. A quantitative analysis of normalized transcript levels on the former tissues allowed the identification of four quadriceps muscle genes (Actb, Gapdh, Ppia and Srp72 that were found to significantly correlate with PMI. These results allowed us to develop a mathematical model with predictive value for estimation of the PMI (confidence interval of ±51 minutes at 95% that can become an important complementary tool for traditional methods.

  16. Burned bodies: post-mortem computed tomography, an essential tool for modern forensic medicine.

    Science.gov (United States)

    Coty, J-B; Nedelcu, C; Yahya, S; Dupont, V; Rougé-Maillart, C; Verschoore, M; Ridereau Zins, C; Aubé, C

    2018-06-07

    Currently, post-mortem computed tomography (PMCT) has become an accessible and contemporary tool for forensic investigations. In the case of burn victims, it provides specific semiologies requiring a prudent understanding to differentiate between the normal post-mortem changes from heat-related changes. The aim of this pictorial essay is to provide to the radiologist the keys to establish complete and focused reports in cases of PMCT of burn victims. Thus, the radiologist must discern all the contextual divergences with the forensic history, and must be able to report all the relevant elements to answer to the forensic pathologist the following questions: Are there tomographic features that could help to identify the victim? Is there evidence of remains of biological fluids in liquid form available for toxicological analysis and DNA sampling? Is there another obvious cause of death than heat-related lesions, especially metallic foreign bodies of ballistic origin? Finally, what are the characteristic burn-related injuries seen on the corpse that should be sought during the autopsy? • CT is highly useful to find features permitting the identification of a severely burned body. • PMCT is a major asset in gunshot injuries to depict ballistic foreign bodies in the burned cadavers. • CT is able to recognise accessible blood for tests versus heat clot (air-crescent sign). • Heat-related fractures are easily differentiated from traumatic fractures. • Epidural collections with a subdural appearance are typical heat-related head lesions.

  17. Comparison of diagnostic performance for perinatal and paediatric post-mortem imaging: CT versus MRI

    International Nuclear Information System (INIS)

    Arthurs, Owen J.; Jacques, Thomas S.; Sebire, Neil J.; Guy, Anna; Chong, W.K.; Gunny, Roxanna; Saunders, Dawn; Olsen, Oystein E.; Thayyil, Sudhin; Wade, Angie; Jones, Rod; Norman, Wendy; Taylor, Andrew M.; Scott, Rosemary; Robertson, Nicola J.; Owens, Catherine M.; Offiah, Amaka C.; Chitty, Lyn S.

    2016-01-01

    To compare the diagnostic yield of whole-body post-mortem computed tomography (PMCT) imaging to post-mortem magnetic resonance (PMMR) imaging in a prospective study of fetuses and children. We compared PMCT and PMMR to conventional autopsy as the gold standard for the detection of (a) major pathological abnormalities related to the cause of death and (b) all diagnostic findings in five different body organ systems. Eighty two cases (53 fetuses and 29 children) underwent PMCT and PMMR prior to autopsy, at which 55 major abnormalities were identified. Significantly more PMCT than PMMR examinations were non-diagnostic (18/82 vs. 4/82; 21.9 % vs. 4.9 %, diff 17.1 % (95 % CI 6.7, 27.6; p < 0.05)). PMMR gave an accurate diagnosis in 24/55 (43.64 %; 95 % CI 31.37, 56.73 %) compared to 18/55 PMCT (32.73 %; 95 % CI 21.81, 45.90). PMCT was particularly poor in fetuses <24 weeks, with 28.6 % (8.1, 46.4 %) more non-diagnostic scans. Where both PMCT and PMMR were diagnostic, PMMR gave slightly higher diagnostic accuracy than PMCT (62.8 % vs. 59.4 %). Unenhanced PMCT has limited value in detection of major pathology primarily because of poor-quality, non-diagnostic fetal images. On this basis, PMMR should be the modality of choice for non-invasive PM imaging in fetuses and children. (orig.)

  18. Diagnostic accuracy and limitations of post-mortem MRI for neurological abnormalities in fetuses and children

    International Nuclear Information System (INIS)

    Arthurs, O.J.; Thayyil, S.; Pauliah, S.S.; Jacques, T.S.; Chong, W.K.; Gunny, R.; Saunders, D.; Addison, S.; Lally, P.; Cady, E.; Jones, R.; Norman, W.; Scott, R.; Robertson, N.J.; Wade, A.; Chitty, L.; Taylor, A.M.

    2015-01-01

    Aim: To compare the diagnostic accuracy of non-invasive cerebral post-mortem magnetic resonance imaging (PMMRI) specifically for cerebral and neurological abnormalities in a series of fetuses and children, compared to conventional autopsy. Materials and methods: Institutional ethics approval and parental consent was obtained. Pre-autopsy cerebral PMMRI was performed in a sequential prospective cohort (n = 400) of fetuses (n = 277; 185 ≤ 24 weeks and 92 > 24 weeks gestation) and children <16 years (n = 123) of age. PMMRI and conventional autopsy findings were reported blinded and independently of each other. Results: Cerebral PMMRI had sensitivities and specificities (95% confidence interval) of 88.4% (75.5 to 94.9), and 95.2% (92.1 to 97.1), respectively, for cerebral malformations; 100% (83.9 to 100), and 99.1% (97.2 to 99.7) for major intracranial bleeds; and 87.5% (80.1 to 92.4) and 74.1% (68 to 79.4) for overall brain pathology. Formal neuropathological examination was non-diagnostic due to maceration/autolysis in 43/277 (16%) fetuses; of these, cerebral PMMRI imaging provided clinically important information in 23 (53%). The sensitivity of PMMRI for detecting significant ante-mortem ischaemic injury was only 68% (48.4 to 82.8) overall. Conclusions: PMMRI is an accurate investigational technique for identifying significant neuropathology in fetuses and children, and may provide important information even in cases where autolysis prevents formal neuropathological examination; however, PMMRI is less sensitive at detecting hypoxic–ischaemic brain injury, and may not detect rarer disorders not encountered in this study. -- Highlights: •Post mortem MRI (PMMRI) has a sensitivity of >87% for detecting cerebral malformations, intracranial bleeds and neurological cause of death. •PMMRI provides important diagnostic information in >50% of fetuses where conventional brain autopsy is non-diagnostic. •PMMRI is currently poor at reliably identifying

  19. The social life of the dead: The role of post-mortem examinations in medical student socialisation.

    Science.gov (United States)

    Goodwin, Dawn; Machin, Laura; Taylor, Adam

    2016-07-01

    Dissection has held a privileged position in medical education although the professional values it inculcates have been subject to intense debate. Claims vary from it generating a dehumanising level of emotional detachment, to promotion of rational and dispassionate decision-making, even to being a positive vehicle for ethical education. Social scientists have positioned dissection as a critical experience in the emotional socialisation of medical students. However, curricular revision has provoked debate about the style and quantity of anatomy teaching thus threatening this 'rite of passage' of medical students. Consequently, some UK medical schools do not employ dissection at all. In its place, observation of post-mortem examinations - a long established, if underutilised, practice - has re-emerged in an attempt to recoup aspects of anatomical knowledge that are arguably lost when dissection is omitted. Bodies for post-mortem examinations and bodies for dissection, however, have striking differences, meaning that post-mortem examinations and dissection cannot be considered comparable opportunities to learn anatomy. In this article, we explore the distinctions between dissection and post-mortem examinations. In particular, we focus on the absence of a discourse of consent, concerns about bodily integrity, how the body's shifting ontology, between object and person, disrupts students' attempts to distance themselves, and how the observation of post-mortem examinations features in the emotional socialisation of medical students. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The toxicological significance of post-mortem drug concentrations in bile.

    Science.gov (United States)

    Ferner, Robin E; Aronson, Jeffrey K

    2018-01-01

    Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value. To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature. We made a systematic search of EMBASE 1980-2016 using the search terms ("bile/" OR "exp drug bile level/concentration/") AND "drug blood level/concentration/", PubMed 1975-2017 for ("bile[tw]" OR "biliary[tw]") AND ("concentration[tw]" OR "concentrations[tw]" OR "level[tw]" OR "levels[tw]") AND "post-mortem[tw]" and also MEDLINE 1990-2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs. Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058-0.32) for dextromoramide to 520 (range 0.62-43,000) for buprenorphine. Median bile

  1. Gamma-hydroxybutyric acid endogenous production and post-mortem behaviour - the importance of different biological matrices, cut-off reference values, sample collection and storage conditions.

    Science.gov (United States)

    Castro, André L; Dias, Mário; Reis, Flávio; Teixeira, Helena M

    2014-10-01

    Gamma-Hydroxybutyric Acid (GHB) is an endogenous compound with a story of clinical use, since the 1960's. However, due to its secondary effects, it has become a controlled substance, entering the illicit market for recreational and "dance club scene" use, muscle enhancement purposes and drug-facilitated sexual assaults. Its endogenous context can bring some difficulties when interpreting, in a forensic context, the analytical values achieved in biological samples. This manuscript reviewed several crucial aspects related to GHB forensic toxicology evaluation, such as its post-mortem behaviour in biological samples; endogenous production values, whether in in vivo and in post-mortem samples; sampling and storage conditions (including stability tests); and cut-off reference values evaluation for different biological samples, such as whole blood, plasma, serum, urine, saliva, bile, vitreous humour and hair. This revision highlights the need of specific sampling care, storage conditions, and cut-off reference values interpretation in different biological samples, essential for proper practical application in forensic toxicology. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  2. Histological transformations of the dental pulp as possible indicator of post mortem interval: a pilot study.

    Science.gov (United States)

    Carrasco, Patricio A; Brizuela, Claudia I; Rodriguez, Ismael A; Muñoz, Samuel; Godoy, Marianela E; Inostroza, Carolina

    2017-10-01

    The correct estimation of the post mortem interval (PMI) can be crucial on the success of a forensic investigation. Diverse methods have been used to estimate PMI, considering physical changes that occur after death, such as mortis algor, livor mortis, among others. Degradation after death of dental pulp is a complex process that has not yet been studied thoroughly. It has been described that pulp RNA degradation could be an indicator of PMI, however this study is limited to 6 days. The tooth is the hardest organ of the human body, and within is confined dental pulp. The pulp morphology is defined as a lax conjunctive tissue with great sensory innervation, abundant microcirculation and great presence of groups of cell types. The aim of this study is to describe the potential use of pulp post mortem alterations to estimate PMI, using a new methodology that will allow obtainment of pulp tissue to be used for histomorphological analysis. The current study will identify potential histological indicators in dental pulp tissue to estimate PMI in time intervals of 24h, 1 month, 3 months and 6 months. This study used 26 teeth from individuals with known PMI of 24h, 1 month, 3 months or 6 months. All samples were manipulated with the new methodology (Carrasco, P. and Inostroza C. inventors; Universidad de los Andes, assignee. Forensic identification, post mortem interval estimation and cause of death determination by recovery of dental tissue. United State patent US 61/826,558 23.05.2013) to extract pulp tissue without the destruction of the tooth. The dental pulp tissues obtained were fixed in formalin for the subsequent generation of histological sections, stained with Hematoxylin Eosin and Masson's Trichrome. All sections were observed under an optical microscope using magnifications of 10× and 40×. The microscopic analysis of the samples showed a progressive transformation of the cellular components and fibers of dental pulp along PMI. These results allowed creating a

  3. Diagnosis of porcine enzootic pneumonia by post mortem sanitary inspection: comparison with other diagnostic methods

    Directory of Open Access Journals (Sweden)

    Kênia de Fátima Carrijo

    2014-06-01

    Full Text Available ABSTRACT. Carrijo K.F., Nascimento E.R., Pereira V.L.A., Morés N., Klein, C.S., Domingues L.M. & Tortelly R. [Diagnosis of porcine enzootic pneumonia by post mortem sanitary inspection: comparison with other diagnostic methods.] Diagnóstico da pneumonia enzoótica suína pela inspeção sanitária post mortem: comparação com outros métodos de diagnóstico. Revista Brasileira de Veterinária Brasileira 36(2:188-194, 2014. Faculdade de Medicina Veterinária, Universidade Federal de Uberlândia, Av. Pará, 1720, Bloco 2T, Jardim Umuarama, Uberlândia, MG 38400-902, Brasil. E-mail: keniacarrijo@ famev.ufu.br To compare the concordance of the diagnosis of porcine enzootic pneumonia (PEP by post-mortem Sanitary Inspection with other methods (histophatology and immunohistochemistry - IHC, were used lung tissue samples from 100 pigs slaughtered under sanitary inspection, and 50 of these had macroscopic lesions suggestive of PEP and 50 had no such lesions. These were fixed in 10% buffered formalin and processed by routine procedures for paraffin embedding and IHC technique for Mycoplasma hyopneumoniae using a monoespecific polyclonal antibody. The study demonstrating that there is concordance between the diagnosis of Sanitary Inspection with histophatology, between the diagnosis of Sanitary Inspection with IHC and histophatology with IHC. It can be conclude that when the lung has gross lesions of PEP, the probability the result is positive to M. hyopneumoniae by IHC and the presence of microscopic lesions increases. Thus, the microscopic diagnosis for PEP is feasible because it is associated to the other, so that the diagnosis given by the officials of Sanitary Inspection in slaughterhouses is not wrong; the macroscopic diagnosis is therefore a valid method for the diagnosis of PEP, it being understood this is not to say that the detection of M. hyopneumoniae.

  4. Post-mortem diagnosis of chronic Chagas's disease comparative evaluation of three serological tests on pericardial fluid.

    Science.gov (United States)

    Lopes, E R; Chapadeiro, E; Batista, S M; Cunha, J G; Rocha, A; Miziara, L; Ribeiro, J U; Patto, R J

    1978-01-01

    In an attempt to improve the post-mortem diagnosis of Chagas's disease the authors performed haemagglutination tests (HAT), fluorescent Trypanosoma cruzi antibody tests (FAT), and complement fixation tests (CFT) on the pericardial fluid obtained at autopsy of 50 individuals with Chagas's heart disease, and 93 patients in whom this disease was not thought to be present. The results demonstrate that all three tests are efficient for the post-mortem diagnosis of Chagas's disease but suggest that their combined use would detect more cases than would one isolated reaction only.

  5. Abnormal fetal cerebral laminar organization in cobblestone complex as seen on post-mortem MRI and DTI

    International Nuclear Information System (INIS)

    Widjaja, Elysa; Geibprasert, Sasikhan; Blaser, Susan; Rayner, Tammy; Shannon, Patrick

    2009-01-01

    We report a unique case of cobblestone complex using post-mortem MR and diffusion tensor imaging to assess the laminar organization of the fetal cerebrum. The imaging findings were correlated with autopsy findings. Abnormal cortical development in cobblestone complex resulted in disruption of normal laminar organization of the fetal brain, which was seen as interruption and nodularity of the high-signal T1 cortical band with increased anisotropy and medium diffusivity extending beyond the cortical band into the cerebral mantle on post-mortem MR and diffusion tensor imaging. (orig.)

  6. Abnormal fetal cerebral laminar organization in cobblestone complex as seen on post-mortem MRI and DTI

    Energy Technology Data Exchange (ETDEWEB)

    Widjaja, Elysa; Geibprasert, Sasikhan; Blaser, Susan; Rayner, Tammy [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto (Canada); Shannon, Patrick [University of Toronto, Department of Pathology, Mount Sinai Hospital, Toronto (Canada)

    2009-08-15

    We report a unique case of cobblestone complex using post-mortem MR and diffusion tensor imaging to assess the laminar organization of the fetal cerebrum. The imaging findings were correlated with autopsy findings. Abnormal cortical development in cobblestone complex resulted in disruption of normal laminar organization of the fetal brain, which was seen as interruption and nodularity of the high-signal T1 cortical band with increased anisotropy and medium diffusivity extending beyond the cortical band into the cerebral mantle on post-mortem MR and diffusion tensor imaging. (orig.)

  7. The effect of stress and exercise on post-mortem biochemistry of Atlantic salmon and rainbow trout

    DEFF Research Database (Denmark)

    Thomas, P.M.; Pankhurst, N.W.; Bremner, Allan

    1999-01-01

    Freshwater Atlantic salmon Salmo salar and rainbow trout Oncorhynchus mykiss responded similarly to increase in water flow (exercise), reduction in holding tank water level (stress), or 30 min chasing with water level reduction (stress and exercise). Stress generally resulted in elevated plasma c...... and exercise, results in mostly transient changes in post-mortem muscle biochemistry. These changes lead to an earlier onset and resolution of rigor, and lower post-mortem muscle pH in comparison to the control. (C) 1999 The Fisheries Society of the British Isles...

  8. [Acceptance of post-mortem organ donation in Germany : Representative cross-sectional study].

    Science.gov (United States)

    Tackmann, E; Dettmer, S

    2018-02-01

    The German post-mortem organ donation rate has dropped by one third since 2010. Furthermore, 958 patients died in 2015 in Germany while waiting for an organ. To decrease organ shortage, an amendment of the transplantation law was established in 2012. An information package including an organ donor card is sent to all German citizens via the postal service. A voluntary national transplantation register was introduced in 2016 to improve transparency in the organ donation process. The influence of several transplantation scandals starting in 2012 on organ donation rates is in question. Therefore, the objective of this article is to discuss approval and objections to post-mortem organ donation among the next of kin of potential donors and the general public in Germany. Binary logistic regression of data from the 2014 survey by the Federal Centre for Health Education on attitudes towards organ and tissue donation in Germany was conducted, aiming to identify influencing factors on the likelihood of organ donor card possession. Additionally, data of the German Organ Transplantation Foundation on post-mortem organ donations in Germany in 2014 were studied to highlight reasons for approval and objections by next of kin of potential and explanted post-mortem organ donors. Methods of documentation of the deceased's will according to data of the German Organ Transplantation Foundation were analyzed. Male gender and lack of knowledge about organ donation decrease the likelihood of having an organ donor card. Of the respondents in the survey of the Federal Centre for Health Education 71.0% would donate their own organs, whereas only one third possess an organ donor card. Health insurances and physicians are the most important providers of organ donor cards in Germany. An increase in the percentage of organ donor card possession following the amendment of the transplantation law could not be observed by 2016. Fear of organ trade and unjust organ allocation are the main reasons

  9. Fuel retention in JET ITER-Like Wall from post-mortem analysis

    Energy Technology Data Exchange (ETDEWEB)

    Heinola, K., E-mail: kalle.heinola@ccfe.ac.uk [Association EURATOM-TEKES, University of Helsinki, PO Box 64, 00560 Helsinki (Finland); EURATOM/CCFE Fusion Association, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Widdowson, A. [EURATOM/CCFE Fusion Association, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Likonen, J. [Association EURATOM-TEKES, VTT, PO Box 1000, 02044 VTT, Espoo (Finland); Alves, E. [Instituto Superior Tecnico, Instituto de Plasmas e Fusao Nuclear, Universidade de Lisboa, 1049-001 Lisboa (Portugal); Baron-Wiechec, A. [EURATOM/CCFE Fusion Association, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Barradas, N. [Instituto Superior Tecnico, Instituto de Plasmas e Fusao Nuclear, Universidade de Lisboa, 1049-001 Lisboa (Portugal); Brezinsek, S. [Forschungszentrum Julich GmbH, EURATOM Association, D-52425 Julich (Germany); Catarino, N. [Instituto Superior Tecnico, Instituto de Plasmas e Fusao Nuclear, Universidade de Lisboa, 1049-001 Lisboa (Portugal); Coad, P. [EURATOM/CCFE Fusion Association, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Koivuranta, S. [Association EURATOM-TEKES, VTT, PO Box 1000, 02044 VTT, Espoo (Finland); Matthews, G.F. [EURATOM/CCFE Fusion Association, Culham Science Centre, Abingdon OX14 3DB (United Kingdom); Mayer, M. [Max-Planck Institut fur Plasmaphysik, EURATOM Association, D-85748 Garching (Germany); Petersson, P. [Royal Institute of Technology, Association EURATOM-VR, SE-10044 Stockholm (Sweden)

    2015-08-15

    Selected Ion Beam Analysis techniques applicable for detecting deuterium and heavier impurities have been used in the post-mortem analyses of tiles removed after the first JET ITER-Like Wall (JET-ILW) campaign. Over half of the retained fuel was measured in the divertor region. The highest figures for fuel retention were obtained from regions with the thickest deposited layers, i.e. in the inner divertor on top of tile 1 and on the High Field Gap Closure tile, which resides deep in the plasma scrape-off layer. Least retention was found in the main chamber high erosion regions, i.e. in the mid-plane of Inner Wall Guard Limiter. The fuel retention values found typically varied with deposition layer thicknesses. The reported retention values support the observed decrease in fuel retention obtained with gas balance experiments of JET-ILW.

  10. Plug-in Based Analysis Framework for LHC Post-Mortem Analysis

    CERN Document Server

    Gorbonosov, R; Zerlauth, M; Baggiolini, V

    2014-01-01

    Plug-in based software architectures [1] are extensible, enforce modularity and allow several teams to work in parallel. But they have certain technical and organizational challenges, which we discuss in this paper. We gained our experience when developing the Post-Mortem Analysis (PMA) system, which is a mission critical system for the Large Hadron Collider (LHC). We used a plugin-based architecture with a general-purpose analysis engine, for which physicists and equipment experts code plugins containing the analysis algorithms. We have over 45 analysis plugins developed by a dozen of domain experts. This paper focuses on the design challenges we faced in order to mitigate the risks of executing third-party code: assurance that even a badly written plugin doesn't perturb the work of the overall application; plugin execution control which allows to detect plugin misbehaviour and react; robust communication mechanism between plugins, diagnostics facilitation in case of plugin failure; testing of the plugins be...

  11. Pregnant woman and road safety: experimental crash test with post mortem human subject.

    Science.gov (United States)

    Delotte, Jerome; Behr, Michel; Thollon, Lionel; Arnoux, Pierre-Jean; Baque, Patrick; Bongain, Andre; Brunet, Christian

    2008-05-01

    Trauma affect between 3 and 7% of all pregnancies in industrialized countries, and the leading cause of these traumas is car crashes. The difficulty to appreciate physiologic and anatomic changes occurring during pregnancy explain that majority of studies were not based on anatomical data. We present a protocol to create a realistic anatomical model of pregnant woman using a post mortem human subject (PMHS). We inserted a physical model of the gravid uterus into the pelvis of a PMHS. 3D acceleration sensors were placed on the subject to measure the acceleration on different body segments. We simulated three frontal impact situations at 20 km/h between two average European cars. Two main kinematics events were identified as possible causes of injuries: lap belt loading and backrest impact. Cadaver experiments provide one interesting complementary approach to study injury mechanisms related to road accidents involving pregnant women. This anatomical accuracy makes it possible to progress in the field of safety devices.

  12. Hypothermic death: Possibility of diagnosis by post-mortem computed tomography

    International Nuclear Information System (INIS)

    Kawasumi, Yusuke; Onozuka, Naoki; Kakizaki, Ayana; Usui, Akihito; Hosokai, Yoshiyuki; Sato, Miho; Saito, Haruo; Ishibashi, Tadashi; Hayashizaki, Yoshie; Funayama, Masato

    2013-01-01

    Referring to our experience with post-mortem computed tomography (CT), many hypothermic death cases presented a lack of increase in lung-field concentration, blood clotting in the heart, thoracic aorta or pulmonary artery, and urine retention in the bladder. Thus we evaluated the diagnostic performance of post-mortem CT on hypothermic death based on the above-mentioned three findings. Twenty-four hypothermic death subjects and 53 non-hypothermic death subjects were examined. Two radiologists assessed the presence or lack of an increase in lung-field concentration, blood clotting in the heart, thoracic aorta or pulmonary artery, and measured urine volume in the bladder. Pearson's chi-square test and Mann–Whitney U-test were used to assess the relationship between the three findings and hypothermic death. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the diagnosis were also calculated. Lack of an increase in lung-field concentration and blood clotting in the heart, thoracic aorta or pulmonary artery were significantly associated with hypothermic death (p = 0.0007, p < 0.0001, respectively). The hypothermic death cases had significantly more urine in the bladder than the non-hypothermic death cases (p = 0.0011). Regarding the diagnostic performance with all three findings, the sensitivity was 29.2% but the specificity was 100%. These three findings were more common in hypothermic death cases. Although the sensitivity was low, these findings will assist forensic physicians in diagnosing hypothermic death since the specificity was high

  13. The influence of body temperature on image contrast in post mortem MRI

    International Nuclear Information System (INIS)

    Ruder, Thomas D.; Hatch, Gary M.; Siegenthaler, Lea; Ampanozi, Garyfalia; Mathier, Sandra; Thali, Michael J.; Weber, Oliver M.

    2012-01-01

    Objective: To assess the temperature dependency of tissue contrast on post mortem magnetic resonance (PMMR) images both objectively and subjectively; and to visually demonstrate the changes of image contrast at various temperatures. Materials and methods: The study was approved by the responsible justice department and the ethics committee. The contrast of water, fat, and muscle was measured using regions of interest (ROI) in the orbit of 41 human corpses to assess how body temperature (range 2.1–39.8 °C) relates to image contrast of T1-weighted (T1W) and T2-weighted (T2W) sequences on PMMR. Regressions were calculated using the method of least squares. Three readers judged visible changes of image contrast subjectively by consensus. Results: There was a positive relationship between temperature and contrast on T1-weighted (T1W) images and between temperature and the contrast of fat/muscle on T2-weighted (T2W) images. There was a negative relationship between temperature and the contrast of water/fat and water/muscle on T2W images. Subjectively, the influence of temperature became visible below 20 °C on T2W images, and below 10 °C on T1W images. Conclusion: Image contrast on PMMR depends on the temperature of a corpse. Radiologists involved in post mortem imaging must be aware of temperature-related changes in MR image contrast. To preserve technical quality, scanning corpses below 10 °C should be avoided.

  14. Hypothermic death: possibility of diagnosis by post-mortem computed tomography.

    Science.gov (United States)

    Kawasumi, Yusuke; Onozuka, Naoki; Kakizaki, Ayana; Usui, Akihito; Hosokai, Yoshiyuki; Sato, Miho; Saito, Haruo; Ishibashi, Tadashi; Hayashizaki, Yoshie; Funayama, Masato

    2013-02-01

    Referring to our experience with post-mortem computed tomography (CT), many hypothermic death cases presented a lack of increase in lung-field concentration, blood clotting in the heart, thoracic aorta or pulmonary artery, and urine retention in the bladder. Thus we evaluated the diagnostic performance of post-mortem CT on hypothermic death based on the above-mentioned three findings. Twenty-four hypothermic death subjects and 53 non-hypothermic death subjects were examined. Two radiologists assessed the presence or lack of an increase in lung-field concentration, blood clotting in the heart, thoracic aorta or pulmonary artery, and measured urine volume in the bladder. Pearson's chi-square test and Mann-Whitney U-test were used to assess the relationship between the three findings and hypothermic death. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the diagnosis were also calculated. Lack of an increase in lung-field concentration and blood clotting in the heart, thoracic aorta or pulmonary artery were significantly associated with hypothermic death (p=0.0007, p<0.0001, respectively). The hypothermic death cases had significantly more urine in the bladder than the non-hypothermic death cases (p=0.0011). Regarding the diagnostic performance with all three findings, the sensitivity was 29.2% but the specificity was 100%. These three findings were more common in hypothermic death cases. Although the sensitivity was low, these findings will assist forensic physicians in diagnosing hypothermic death since the specificity was high. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Hypothermic death: Possibility of diagnosis by post-mortem computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kawasumi, Yusuke, E-mail: ssu@rad.med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Clinical Imaging, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 (Japan); Onozuka, Naoki; Kakizaki, Ayana [Tohoku University Graduate School of Medicine, Department of Clinical Imaging, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 (Japan); Usui, Akihito, E-mail: t7402r0506@med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Diagnostic Image Analysis, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 (Japan); Hosokai, Yoshiyuki, E-mail: hosokai@med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Diagnostic Image Analysis, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 (Japan); Sato, Miho, E-mail: meifan58@m.tains.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Clinical Imaging, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 (Japan); Saito, Haruo, E-mail: hsaito@med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Diagnostic Image Analysis, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 (Japan); Ishibashi, Tadashi, E-mail: tisibasi@med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Clinical Imaging, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 (Japan); Hayashizaki, Yoshie, E-mail: yoshie@forensic.med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Forensic Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 (Japan); Funayama, Masato, E-mail: funayama@forensic.med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Forensic Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 (Japan)

    2013-02-15

    Referring to our experience with post-mortem computed tomography (CT), many hypothermic death cases presented a lack of increase in lung-field concentration, blood clotting in the heart, thoracic aorta or pulmonary artery, and urine retention in the bladder. Thus we evaluated the diagnostic performance of post-mortem CT on hypothermic death based on the above-mentioned three findings. Twenty-four hypothermic death subjects and 53 non-hypothermic death subjects were examined. Two radiologists assessed the presence or lack of an increase in lung-field concentration, blood clotting in the heart, thoracic aorta or pulmonary artery, and measured urine volume in the bladder. Pearson's chi-square test and Mann–Whitney U-test were used to assess the relationship between the three findings and hypothermic death. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the diagnosis were also calculated. Lack of an increase in lung-field concentration and blood clotting in the heart, thoracic aorta or pulmonary artery were significantly associated with hypothermic death (p = 0.0007, p < 0.0001, respectively). The hypothermic death cases had significantly more urine in the bladder than the non-hypothermic death cases (p = 0.0011). Regarding the diagnostic performance with all three findings, the sensitivity was 29.2% but the specificity was 100%. These three findings were more common in hypothermic death cases. Although the sensitivity was low, these findings will assist forensic physicians in diagnosing hypothermic death since the specificity was high.

  16. Methods in Clinical Pharmacology Series

    Science.gov (United States)

    Beaumont, Claire; Young, Graeme C; Cavalier, Tom; Young, Malcolm A

    2014-01-01

    Human radiolabel studies are traditionally conducted to provide a definitive understanding of the human absorption, distribution, metabolism and excretion (ADME) properties of a drug. However, advances in technology over the past decade have allowed alternative methods to be employed to obtain both clinical ADME and pharmacokinetic (PK) information. These include microdose and microtracer approaches using accelerator mass spectrometry, and the identification and quantification of metabolites in samples from classical human PK studies using technologies suitable for non-radiolabelled drug molecules, namely liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. These recently developed approaches are described here together with relevant examples primarily from experiences gained in support of drug development projects at GlaxoSmithKline. The advantages of these study designs together with their limitations are described. We also discuss special considerations which should be made for a successful outcome to these new approaches and also to the more traditional human radiolabel study in order to maximize knowledge around the human ADME properties of drug molecules. PMID:25041729

  17. Electronic cigarettes and nicotine clinical pharmacology

    OpenAIRE

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abst...

  18. Post-mortem changes in chicken muscle : some key biochemical processes involved in the conversion of muscle to meat

    NARCIS (Netherlands)

    Schreurs, F.J.G.

    1999-01-01

    The post mortem changes taking place in poultry muscular tissue and the resulting meat quality, until the moment of consumption of the meat by the consumer are described. Modern broiler chickens grow 'at the edge of what is metabolically possible'. This hypothesis is derived from the fact

  19. Effect of cooling rate upon processing characteristics of pork meat of different glycolysis type during post mortem ageing.

    Science.gov (United States)

    Vada, M

    1977-10-01

    Rapid chilling was applied to porcine longissimus dorsi muscles at 1 h post mortem in order to observe its effect on the quality of canned products prepared from those of different pH(1) values. The muscle from one side of each animal was removed from the carcase 50 minutes post mortem and divided into two longitudinal strips. One was chilled immediately to 13-15°C (1 h post mortem): the other after a further hour (2 h post mortem) acted as control. After the centre temperature had reached 10°C the muscles were stored in a refrigerator at 3-5°C. Compared with the control samples (chilled at 2 h p.m.), rapid chilling from 1 h p.m. caused an improvement in the water-holding capacity and the texture of pork meat, which had higher pH(1) values and was processed at 2, 4 and 48 h p.m. There was minimum brine retention and texture score if samples-both rapidly chilled and control-were processed at 24 h p.m. Although brine retention of PSE pork meat could not be increased even by rapid chilling, the texture of heat treated PSE pork showed an improvement during storage, which was more pronounced after ageing for 48 h, if PSE samples were chilled at 1 h p.m. Copyright © 1977. Published by Elsevier Ltd.

  20. Identification of discrete vascular lesions in the extremities using post-mortem computed tomography angiography – Case reports

    NARCIS (Netherlands)

    Haakma, Wieke; Rohde, Marianne; Uhrenholt, Lars; Pedersen, Michael; Boel, Lene Warner Thorup

    2017-01-01

    In this case report, we introduced post-mortem computed tomography angiography (PMCTA) in three cases suffering from vascular lesions in the upper extremities. In each subject, the third part of the axillary arteries and veins were used to catheterize the arms. The vessels were filled with a barium

  1. Post-mortem computed tomography angiography utilizing barium sulfate to identify microvascular structures : a preliminary phantom model and case study

    NARCIS (Netherlands)

    Haakma, Wieke; Rohde, Marianne; Kuster, Lidy; Uhrenholt, Lars; Pedersen, Michael; Boel, Lene Warner Thorup

    2016-01-01

    We investigated the use of computer tomography angiography (CTA) to visualize microvascular structures in a vessel-mimicking phantom and post-mortem (PM) bodies. A contrast agent was used based on 22% barium sulfate, 20% polyethylene glycol and 58% distilled water. A vessel-mimicking phantom

  2. Corroboration of in utero MRI using post-mortem MRI and autopsy in foetuses with CNS abnormalities

    International Nuclear Information System (INIS)

    Whitby, E.H.; Variend, S.; Rutter, S.; Paley, M.N.J.; Wilkinson, I.D.; Davies, N.P.; Sparey, C.; Griffiths, P.D.

    2004-01-01

    AIMS: To corroborate the findings of in utero magnetic resonance imaging (MRI) with autopsy and post-mortem MRI in cases of known or suspected central nervous system (CNS) abnormalities on ultrasound and to compare the diagnostic accuracy of ante-natal ultrasound and in utero MRI. METHODS: Twelve pregnant women, whose foetuses had suspected central nervous system abnormalities underwent in utero MRI. The foetuses were imaged using MRi before autopsy. The data were used to evaluate the diagnostic accuracy of in utero MRI when compared with a reference standard of autopsy and post-mortem MRI in 10 cases and post-mortem MRI alone in two cases. RESULTS: The diagnostic accuracy of antenatal ultrasound and in utero MRI in correctly characterizing brain and spine abnormalities were 42 and 100%, respectively. CONCLUSION: In utero MRI provides a useful adjuvant to antenatal ultrasound when assessing CNS abnormalities by providing more accurate anatomical information. Post-mortem MRI assists the diagnosis of macroscopic structural abnormalities

  3. Variation in post mortem rate of glycolyis does not necessarily affect drip loss of non-stimulated veal

    NARCIS (Netherlands)

    Hertog-Meischke, den M.J.; Klont, R.E.; Smulders, F.J.M.; Logtestijn, van J.G.

    1997-01-01

    In this study the effect of the rate of post mortem pH fall on the water-holding capacity of meat from moderately chilled veal carcasses was investigated. Also the relationship between muscle protein denaturation and drip loss of veal was examined. Three groups of 10 Friesian Holstein male veal

  4. External foam and the post-mortem period in freshwater drowning; results from a retrospective study in Amsterdam, the Netherlands.

    Science.gov (United States)

    Reijnen, G; Buster, M C; Vos, P J E; Reijnders, U J L

    2017-11-01

    Determining the time of death of bodies recovered from water can be difficult. A feature of drowning is the presence of external foam. This study describes the presence of external foam in relation to the post-mortem period. The study utilizes a database of death reports dated between January 2011 and July 2016. For bodies recovered from fresh water, the presence or absence of external foam was noted. In this study, 112 death reports are included. Of these reports, 18 mentioned external foam, which account for 16.1% of the entire study population. In the population with a post-mortem period of less than 24 h, external foam was detected in 27.7% of cases. All 18 incidents with external foam had an estimated post-mortem period of less than 24 h. In our study, external foam was only present in freshwater drowning cases with a post-mortem period of less than 24 h. Based on this finding, the presence of external foam may be useful as an additional indicator when estimating the time of death in freshwater drowning. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  5. Can we infer post mortem interval on the basis of decomposition rate? A case from a Portuguese cemetery.

    Science.gov (United States)

    Ferreira, M Teresa; Cunha, Eugénia

    2013-03-10

    Post mortem interval estimation is crucial in forensic sciences for both positive identification and reconstruction of perimortem events. However, reliable dating of skeletonized remains poses a scientific challenge since human remains decomposition involves a set of complex and highly variable processes. Many of the difficulties in determining post mortem interval and/or the permanence of a body in a specific environment relates with the lack of systematic observations and research in human body decomposition modalities in different environments. In March 2006, in order to solve a problem of misidentification, a team of the South Branch of Portuguese National Institute of Legal Medicine carried out the exhumation of 25 identified individuals buried for almost five years in the same cemetery plot. Even though all individuals shared similar post mortem intervals, they presented different stages of decomposition. In order to analyze the post mortem factors associated with the different stages of decomposition displayed by the 25 exhumed individuals, the stages of decomposition were scored. Information regarding age at death and sex of the individuals were gathered and recorded as well as data in the cause of death and grave and coffin characteristics. Although the observed distinct decay stages may be explained by the burial conditions, namely by the micro taphonomic environments, individual endogenous factors also play an important role on differential decomposition as witnessed by the present case. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. Practical experience in post-mortem tissue donation in consideration of the European tissue law.

    Science.gov (United States)

    Karbe, Thomas; Braun, Christian; Wulff, Birgit; Schröder, Ann Sophie; Püschel, Klaus; Bratzke, Hansjürgen; Parzeller, Markus

    2010-03-01

    In consequence of the European guidelines of safety and quality standards for the donation, retrieval, storing and distribution of human tissues and cells the purpose of tissue transplantation was implemented into German legislation in May 2007. The law came into effect on August 1st 2007 considering of the European rules. The Institutes for Legal Medicine of the University of Frankfurt/Main and the University Medical Center Hamburg-Eppendorf developed a model for tissue retrieval. The Institute of Legal Medicine (I.f.R.) at the University Medical Center Hamburg cooperates with the German Institute of Cell and Tissue Replacement (Deutsches Institut für Zell--und Gewebeersatz DIZG). Potential post-mortem tissue donors (PMTD) among the deceased are selected by standardized sets of defined criteria. The procedure is guided by the intended exclusion criteria of the tissue regulation draft (German Transplant Law TPG GewV) in accordance with the European Guideline (2006/17/EC). Following the identification of the donor and subsequent removal of tissue, the retrieved samples were sent to the DIZG, a non-profit tissue bank according to the tissue regulation. Here the final processing into transplantable tissue grafts takes place, which then results in the allocation of tissue to hospitals in Germany and other European countries. The Center of Legal Medicine at the Johann Wolfgang Goethe-University Medical Center Frankfurt/Main cooperates since 2000 with Tutogen, a pharmaceutical company. Harvesting of musculoskeletal tissues follows corresponding regulations. To verify the outcome of PMTD at the I.f.R. Hamburg, two-statistic analysis over 12 and 4 months have been implemented. Our results have shown an increasing number of potential appropriate PMTD within the second inquiry interval but a relatively small and unvaryingly rate of successful post-mortem tissue retrievals similar to the first examination period. Thus, the aim of the model developed by the I.f.R. is to

  7. [18F]FDDNP PET in Tauopathies: Correlation to post mortem Pathology in a Case of Progressive Supranuclear Palsy (PSP)

    Science.gov (United States)

    Villegas, Brendon Josef

    This investigation of [18F]FDDNP was conducted in an effort to confirm the presence of disease in a patient with Progressive Supranuclear Palsy (PSP) and to correlate the ante mortem PET scan results to the post mortem pathology. The immunohistochemical and immunofluorescent staining of Paired Helical Filamentous (PHF) tau (AT8) and Amyloid Beta (6F/3D) misfolded proteins demonstrated a widespread deposition in the cortical and subcortical nuclei, the white matter, cerebellar white matter and the medulla oblongata. The in vitro autoradiography demonstrated a neocortical signal comprised of well-delineated amyloid beta in the nucleated layers I/II and hyperphosphorylated tau in the deeper layers III through VI. The autoradiography was well correlated with the immunohistochemical staining in adjacent tissue slides. The binding of the parametric [ 18F]FDDNP distribution volume ratio (DVR) correlated well (Spearman's rho = 0.962, p = .004) with the deposition of tau but not with the presence of amyloid beta (Spearman's rho = -0.829, p = .041). The [ 18F]FDDNP DVR signal appears to be primarily due to the large amount of bound hyperphosphorylated tau (p-tau) and the amyloid beta negligibly contributes to the total signal. Unlabeled FDDNP was shown to bind to tau in the form of globose tangles in the rostral ventromedial medulla as confirmed with both Thioflavin S and PHF-tau Immunofluorescence. The binding of [18F]FDDNP to the human neuroanatomy was investigated in two cohorts of distinct tauopathies and compared to the binding in two tau-negative cohorts against control patients. A cohort of PSP patients (n = 12) with a mean age of 63.8 years and a cohort of Chronic Traumatic Encephalopathy (CTE) patients (n = 14) with a mean age of 58.1 years are both characterized by the presence of various degrees of tau pathology in their brains. The cohort of Parkinson's Disease (PD) patients (n = 16) with a mean age of 63.2 years is initially characterized by clinical symptoms

  8. Measurements using 7.0 T post-mortem magnetic resonance imaging of the scalar dimensions of the fetal brain between 12 and 20 weeks gestational age.

    Science.gov (United States)

    Lin, Xiangtao; Zhang, Zhonghe; Teng, Gaojun; Meng, Haiwei; Yu, Taifei; Hou, Zhongyu; Fang, Fang; Zang, Fengchao; Liu, Shuwei

    2011-12-01

    In this study, scalar values for the fetal brain from 12 to 20 weeks gestational age were obtained. Fifty-two fetal specimens of 12-20 weeks gestational age with an anatomically normal and developmentally appropriate central nervous system (CNS) were scanned using a 7.0 T magnetic resonance imaging (MRI) scanner. The linear biometric measurements of the brain were then determined. All the measurements (except for the interhemispheric distance) were found to increase linearly with gestational age, although each increased at a different growth rates. The 95% confidence interval for each value was obtained. These data may be considered to be a valuable reference for the assessment of normal fetal brain development in clinical settings and as a supplement to post-mortem MRI or anatomical investigations. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

  9. Diagnostic accuracy of post-mortem MRI for thoracic abnormalities in fetuses and children

    International Nuclear Information System (INIS)

    Arthurs, Owen J.; Thayyil, Sudhin; Addison, Shea; Olsen, Oystein E.; Wade, Angie; Jones, Rod; Norman, Wendy; Taylor, Andrew M.; Scott, Rosemary J.; Robertson, Nicola J.; Chitty, Lyn S.; Sebire, Neil J.; Owens, Catherine M.

    2014-01-01

    To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for non-cardiac thoracic pathology in fetuses and children, compared with conventional autopsy. Institutional ethics approval and parental consent was obtained. A total of 400 unselected fetuses and children underwent PMMR before conventional autopsy, reported blinded to the other dataset. Of 400 non-cardiac thoracic abnormalities, 113 (28 %) were found at autopsy. Overall sensitivity and specificity (95 % confidence interval) of PMMR for any thoracic pathology was poor at 39.6 % (31.0, 48.9) and 85.5 % (80.7, 89.2) respectively, with positive predictive value (PPV) 53.7 % (42.9, 64.0) and negative predictive value (NPV) 77.0 % (71.8, 81.4). Overall agreement was 71.8 % (67.1, 76.2). PMMR was most sensitive at detecting anatomical abnormalities, including pleural effusions and lung or thoracic hypoplasia, but particularly poor at detecting infection. PMMR currently has relatively poor diagnostic detection rates for the commonest intra-thoracic pathologies identified at autopsy in fetuses and children, including respiratory tract infection and diffuse alveolar haemorrhage. The reasonable NPV suggests that normal thoracic appearances at PMMR exclude the majority of important thoracic lesions at autopsy, and so could be useful in the context of minimally invasive autopsy for detecting non-cardiac thoracic abnormalities. (orig.)

  10. Partial autolysis of μ/m-calpain during post mortem aging of chicken muscle.

    Science.gov (United States)

    Zhao, Liang; Jiang, Nanqi; Li, Miaozhen; Huang, Ming; Zhou, Guanghong

    2016-12-01

    The objective of this study was to investigate changes occurring in μ/m-calpain in post mortem chicken muscles and to determine the origin of the unknown bands found in calpain casein zymography. The unknown bands were reported with slightly greater mobility compared to conventional μ/m-calpain bands in casein zymography. Identification of these bands was accomplished using native polyacrylamide gel electrophoresis, liquid chromatography tandem mass spectrometry and with protein phosphatase treatment. Results showed that the unknown bands were corresponding to μ/m-calpain, and dephosphorylation by protein phosphatase did not change their appearance. The calpain samples were then incubated with various concentrations of Ca 2+ to determine the relationship between changes in μ/m-calpain and the appearance of the unknown bands. The products of μ/m-calpain partial autolysis were found to be consistent with the appearance of the unknown bands. Therefore, the appearance of these bands did not result from phosphorylation of μ/m-calpain as previously hypothesized, but from partial autolysis of μ/m-calpain. Also their presence suggests that μ/m-calpain undergoes partial autolysis during aging which may play certain roles in meat quality improvement. © 2016 Japanese Society of Animal Science.

  11. Re-establishment of rigor mortis: evidence for a considerably longer post-mortem time span.

    Science.gov (United States)

    Crostack, Chiara; Sehner, Susanne; Raupach, Tobias; Anders, Sven

    2017-07-01

    Re-establishment of rigor mortis following mechanical loosening is used as part of the complex method for the forensic estimation of the time since death in human bodies and has formerly been reported to occur up to 8-12 h post-mortem (hpm). We recently described our observation of the phenomenon in up to 19 hpm in cases with in-hospital death. Due to the case selection (preceding illness, immobilisation), transfer of these results to forensic cases might be limited. We therefore examined 67 out-of-hospital cases of sudden death with known time points of death. Re-establishment of rigor mortis was positive in 52.2% of cases and was observed up to 20 hpm. In contrast to the current doctrine that a recurrence of rigor mortis is always of a lesser degree than its first manifestation in a given patient, muscular rigidity at re-establishment equalled or even exceeded the degree observed before dissolving in 21 joints. Furthermore, this is the first study to describe that the phenomenon appears to be independent of body or ambient temperature.

  12. Diagnostic accuracy of post-mortem MRI for thoracic abnormalities in fetuses and children

    Energy Technology Data Exchange (ETDEWEB)

    Arthurs, Owen J. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Radiology, London (United Kingdom); UCL Institute of Child Health, London (United Kingdom); Thayyil, Sudhin; Addison, Shea [Imperial College London, Perinatal Neurology and Neonatology, London (United Kingdom); Olsen, Oystein E. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Radiology, London (United Kingdom); Wade, Angie [UCL Institute of Child Health, Paediatric Epidemiology and Biostatistics Unit, London (United Kingdom); Jones, Rod; Norman, Wendy; Taylor, Andrew M. [UCL Institute of Cardiovascular Science, Centre for Cardiovascular Imaging, London (United Kingdom); Great Ormond Street Hospital for Children NHS Foundation Trust, Cardiorespiratory Division, London (United Kingdom); Scott, Rosemary J. [University College London Hospital NHS Trust, Department of Histopathology, London (United Kingdom); Robertson, Nicola J. [UCL Institute for Women' s Health, Academic Neonatology, London (United Kingdom); Chitty, Lyn S. [UCL Institute of Child Health, Genetics and Genomic Medicine, London (United Kingdom); UCLH NHS Foundation Trusts, London (United Kingdom); Sebire, Neil J. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Histopathology, London (United Kingdom); UCL Institute of Child Health, London (United Kingdom); Owens, Catherine M. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Radiology, London (United Kingdom); UCL Institute of Cardiovascular Science, Centre for Cardiovascular Imaging, London (United Kingdom); Great Ormond Street Hospital for Children NHS Foundation Trust, Cardiorespiratory Division, London (United Kingdom); Collaboration: Magnetic Resonance Imaging Autopsy Study (MaRIAS) Collaborative Group

    2014-11-15

    To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for non-cardiac thoracic pathology in fetuses and children, compared with conventional autopsy. Institutional ethics approval and parental consent was obtained. A total of 400 unselected fetuses and children underwent PMMR before conventional autopsy, reported blinded to the other dataset. Of 400 non-cardiac thoracic abnormalities, 113 (28 %) were found at autopsy. Overall sensitivity and specificity (95 % confidence interval) of PMMR for any thoracic pathology was poor at 39.6 % (31.0, 48.9) and 85.5 % (80.7, 89.2) respectively, with positive predictive value (PPV) 53.7 % (42.9, 64.0) and negative predictive value (NPV) 77.0 % (71.8, 81.4). Overall agreement was 71.8 % (67.1, 76.2). PMMR was most sensitive at detecting anatomical abnormalities, including pleural effusions and lung or thoracic hypoplasia, but particularly poor at detecting infection. PMMR currently has relatively poor diagnostic detection rates for the commonest intra-thoracic pathologies identified at autopsy in fetuses and children, including respiratory tract infection and diffuse alveolar haemorrhage. The reasonable NPV suggests that normal thoracic appearances at PMMR exclude the majority of important thoracic lesions at autopsy, and so could be useful in the context of minimally invasive autopsy for detecting non-cardiac thoracic abnormalities. (orig.)

  13. Breast density quantification with cone-beam CT: a post-mortem study

    International Nuclear Information System (INIS)

    Johnson, Travis; Ding, Huanjun; Le, Huy Q; Ducote, Justin L; Molloi, Sabee

    2013-01-01

    Forty post-mortem breasts were imaged with a flat-panel based cone-beam x-ray CT system at 50 kVp. The feasibility of breast density quantification has been investigated using standard histogram thresholding and an automatic segmentation method based on the fuzzy c-means algorithm (FCM). The breasts were chemically decomposed into water, lipid, and protein immediately after image acquisition was completed. The per cent fibroglandular volume (%FGV) from chemical analysis was used as the gold standard for breast density comparison. Both image-based segmentation techniques showed good precision in breast density quantification with high linear coefficients between the right and left breast of each pair. When comparing with the gold standard using %FGV from chemical analysis, Pearson's r-values were estimated to be 0.983 and 0.968 for the FCM clustering and the histogram thresholding techniques, respectively. The standard error of the estimate was also reduced from 3.92% to 2.45% by applying the automatic clustering technique. The results of the postmortem study suggested that breast tissue can be characterized in terms of water, lipid and protein contents with high accuracy by using chemical analysis, which offers a gold standard for breast density studies comparing different techniques. In the investigated image segmentation techniques, the FCM algorithm had high precision and accuracy in breast density quantification. In comparison to conventional histogram thresholding, it was more efficient and reduced inter-observer variation. (paper)

  14. Cochlear neuropathy in human presbycusis: Confocal analysis of hidden hearing loss in post-mortem tissue.

    Science.gov (United States)

    Viana, Lucas M; O'Malley, Jennifer T; Burgess, Barbara J; Jones, Dianne D; Oliveira, Carlos A C P; Santos, Felipe; Merchant, Saumil N; Liberman, Leslie D; Liberman, M Charles

    2015-09-01

    Recent animal work has suggested that cochlear synapses are more vulnerable than hair cells in both noise-induced and age-related hearing loss. This synaptopathy is invisible in conventional histopathological analysis, because cochlear nerve cell bodies in the spiral ganglion survive for years, and synaptic analysis requires special immunostaining or serial-section electron microscopy. Here, we show that the same quadruple-immunostaining protocols that allow synaptic counts, hair cell counts, neuronal counts and differentiation of afferent and efferent fibers in mouse can be applied to human temporal bones, when harvested within 9 h post-mortem and prepared as dissected whole mounts of the sensory epithelium and osseous spiral lamina. Quantitative analysis of five "normal" ears, aged 54-89 yrs, without any history of otologic disease, suggests that cochlear synaptopathy and the degeneration of cochlear nerve peripheral axons, despite a near-normal hair cell population, may be an important component of human presbycusis. Although primary cochlear nerve degeneration is not expected to affect audiometric thresholds, it may be key to problems with hearing in noise that are characteristic of declining hearing abilities in the aging ear. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Intermittent fasting modulation of the diabetic syndrome in sand rats. III. Post-mortem investigations.

    Science.gov (United States)

    Belkacemi, Louiza; Selselet-Attou, Ghalem; Bulur, Nurdan; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J

    2011-01-01

    The present report concerns several post-mortem variables examined in sand rats that were either maintained on a vegetal diet (control animals) or exposed first during a 20-day transition period to a mixed diet consisting of a fixed amount of a hypercaloric food and decreasing amounts of the vegetal food and then to a 30-day experimental period of exposure to the hypercaloric food. During the latter period, all animals were either given free access to food or fasting daily for 15 h, i.e. from 5.00 p.m. to 8.00 a.m. The body weight, liver wet weight, pancreas wet weight, plasma glucose and haemoglobin A1c concentration, plasma insulin concentration, insulinogenic index, insulin resistance HOMA, plasma cholesterol and triglyceride concentration, liver triglyceride and phospholipid content were all measured. Pancreatic islet (insulin, GLUT2) and liver (lipid droplets) histology were also examined. The main findings consisted in a lower body weight of fasting than non-fasting animals, a higher liver weight in non-diabetic and diabetic rats than in control non-fasting (but not so in fasting) animals, a decrease of pancreas weight in non-diabetic and diabetic as distinct from control animals, a fasting-induced decrease in plasma glucose, plasma insulin and insulin resistance HOMA, plasma cholesterol and triglyceride concentration and triglyceride liver content.

  16. Unusually extensive head trauma in a hydraulic elevator accident: post-mortem MSCT findings, autopsy results and scene reconstruction.

    Science.gov (United States)

    Jacobsen, Christina; Schön, Corinna A; Kneubuehl, Beat; Thali, Michael J; Aghayev, Emin

    2008-10-01

    Accidental or intentional falls from a height are a form of blunt trauma and occur frequently in forensic medicine. Reports describing elevator accidents as a small subcategory of falls from heights are rare in the medical literature and no report on injury patterns or scene reconstruction of such an accident was found. A case of an accident in a hydraulic elevator with a man falling 3m was examined using post-mortem multi-slice computed tomography (MSCT) and autopsy. The man suffered an unusually extensive trauma and died at the scene. Post-mortem MSCT examination showed a comminute fracture of the skull, the right femur and the first lumbar vertebra. Severe lacerations of the brain with epidural, subdural and subarachnoidal haemorrhages over both hemispheres were diagnosed. Autopsy confirmed these findings. To reconstruct the accident we used radiological and autopsy results as well as findings at the scene.

  17. Experimental evaluation of rigor mortis. VII. Effect of ante- and post-mortem electrocution on the evolution of rigor mortis.

    Science.gov (United States)

    Krompecher, T; Bergerioux, C

    1988-01-01

    The influence of electrocution on the evolution of rigor mortis was studied on rats. Our experiments showed that: (1) Electrocution hastens the onset of rigor mortis. After an electrocution of 90 s, a complete rigor develops already 1 h post-mortem (p.m.) compared to 5 h p.m. for the controls. (2) Electrocution hastens the passing of rigor mortis. After an electrocution of 90 s, the first significant decrease occurs at 3 h p.m. (8 h p.m. in the controls). (3) These modifications in rigor mortis evolution are less pronounced in the limbs not directly touched by the electric current. (4) In case of post-mortem electrocution, the changes are slightly less pronounced, the resistance is higher and the absorbed energy is lower as compared with the ante-mortem electrocution cases. The results are completed by two practical observations on human electrocution cases.

  18. Electronic cigarettes and nicotine clinical pharmacology.

    Science.gov (United States)

    Schroeder, Megan J; Hoffman, Allison C

    2014-05-01

    To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products' ability to support and maintain nicotine dependence. Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products' impact on public health.

  19. Electronic cigarettes and nicotine clinical pharmacology

    Science.gov (United States)

    Schroeder, Megan J; Hoffman, Allison C

    2014-01-01

    Objective To review the available literature evaluating electronic cigarette (e-cigarette) nicotine clinical pharmacology in order to understand the potential impact of e-cigarettes on individual users, nicotine dependence and public health. Methods Literature searches were conducted between 1 October 2012 and 30 September 2013 using key terms in five electronic databases. Studies were included in the review if they were in English and publicly available; non-clinical studies, conference abstracts and studies exclusively measuring nicotine content in e-cigarette cartridges were excluded from the review. Results Nicotine yields from automated smoking machines suggest that e-cigarettes deliver less nicotine per puff than traditional cigarettes, and clinical studies indicate that e-cigarettes deliver only modest nicotine concentrations to the inexperienced e-cigarette user. However, current e-cigarette smokers are able to achieve systemic nicotine and/or cotinine concentrations similar to those produced from traditional cigarettes. Therefore, user experience is critically important for nicotine exposure, and may contribute to the products’ ability to support and maintain nicotine dependence. Conclusions Knowledge about e-cigarette nicotine pharmacology remains limited. Because a user's e-cigarette experience may significantly impact nicotine delivery, future nicotine pharmacokinetic and pharmacodynamic studies should be conducted in experienced users to accurately assess the products’ impact on public health. PMID:24732160

  20. Feather retention force in broilers ante-, peri-, and post-mortem as influenced by electrical and carbon dioxide stunning.

    Science.gov (United States)

    Buhr, R J; Cason, J A; Rowland, G N

    1997-11-01

    Stunning and slaughter trials were conducted to evaluate the influence of stunning method (electrical 50 V alternating current, CO2 gas: 0 to 40% for 90 s or 40 to 60% for 30 s) on feather retention force (FRF) in commercial broilers. Feathers from the pectoral, sternal, and femoral feather tracts were sampled with a force gauge before stunning (ante-mortem) and contralaterally either after stunning (peri-mortem from 0.5 to 4 min) or after stunning and bleeding (post-mortem from 2 to 6 min). Prior to stunning, ante-mortem FRF values varied among assigned stunning methods only for the pectoral (7%) feather tract. After stunning, peri-mortem FRF values were higher only for the sternal tract (11% for 40 to 60% CO2 for 30 s); whereas after stunning and bleeding, post-mortem FRF values were lower than ante- or peri-mortem only for the sternal tract (10% lower for 40 to 60% CO2 for 30 s). Peri- and post-mortem FRF values did not differ among stunning methods for the pectoral and femoral feather tracts. Small changes in FRF values occurred from ante-mortem to peri-mortem (-1 to +12%), and from ante-mortem to post-mortem (-2 to +8%) across stunning methods. A significant increase was determined for only the pectoral tract (7%) from ante- to peri-mortem across stunning methods. Electrically stunned broilers that were not bled gained weight in excess of the 36 feathers removed (0.16%), apparently due to body surface water pickup during the brine-stunning process, whereas CO2-stunned broilers lost weight due to excretion of cloacal contents (-0.31 to -0.98%). The change in body weight among stunning methods was significant (P defeathering efficiency may not differ after scalding.

  1. Influence of Post-Mortem Sperm Recovery Method and Extender on Unstored and Refrigerated Rooster Sperm Variables.

    Science.gov (United States)

    Villaverde-Morcillo, S; Esteso, M C; Castaño, C; Santiago-Moreno, J

    2016-02-01

    Many post-mortem sperm collection techniques have been described for mammalian species, but their use in birds is scarce. This paper compares the efficacy of two post-mortem sperm retrieval techniques - the flushing and float-out methods - in the collection of rooster sperm, in conjunction with the use of two extenders, i.e., L&R-84 medium and Lake 7.1 medium. To determine whether the protective effects of these extenders against refrigeration are different for post-mortem and ejaculated sperm, pooled ejaculated samples (procured via the massage technique) were also diluted in the above extenders. Post-mortem and ejaculated sperm variables were assessed immediately at room temperature (0 h), and after refrigeration at 5°C for 24 and 48 h. The flushing method retrieved more sperm than the float-out method (596.5 ± 75.4 million sperm vs 341.0 ± 87.6 million sperm; p < 0.05); indeed, the number retrieved by the former method was similar to that obtained by massage-induced ejaculation (630.3 ± 78.2 million sperm). For sperm collected by all methods, the L&R-84 medium provided an advantage in terms of sperm motility variables at 0 h. In the refrigerated sperm samples, however, the Lake 7.1 medium was associated with higher percentages of viable sperm, and had a greater protective effect (p < 0.05) with respect to most motility variables. In conclusion, the flushing method is recommended for collecting sperm from dead birds. If this sperm needs to be refrigerated at 5°C until analysis, Lake 7.1 medium is recommended as an extender. © 2015 Blackwell Verlag GmbH.

  2. Estimating the Post-Mortem Interval of skeletonized remains: The use of Infrared spectroscopy and Raman spectro-microscopy

    Science.gov (United States)

    Creagh, Dudley; Cameron, Alyce

    2017-08-01

    When skeletonized remains are found it becomes a police task to determine to identify the body and establish the cause of death. It assists investigators if the Post-Mortem Interval (PMI) can be established. Hitherto no reliable qualitative method of estimating the PMI has been found. A quantitative method has yet to be developed. This paper shows that IR spectroscopy and Raman microscopy have the potential to form the basis of a quantitative method.

  3. Quantification of ante-mortem hypoxic ischemic brain injury by post-mortem cerebral magnetic resonance imaging in neonatal encephalopathy.

    Science.gov (United States)

    Montaldo, Paolo; Chaban, Badr; Lally, Peter J; Sebire, Neil J; Taylor, Andrew M; Thayyil, Sudhin

    2015-11-01

    Post-mortem (PM) magnetic resonance imaging (MRI) is increasingly used as an alternative to conventional autopsy in babies dying from neonatal encephalopathy. However, the confounding effect of post-mortem changes on the detection of ante-mortem ischemic injury is unclear. We examined whether quantitative MR measurements can accurately distinguish ante-mortem ischemic brain injury from artifacts using post-mortem MRI. We compared PM brain MRI (1.5 T Siemens, Avanto) in 7 infants who died with neonatal encephalopathy (NE) of presumed hypoxic-ischemic origin with 7 newborn infants who had sudden unexplained neonatal death (SUND controls) without evidence of hypoxic-ischemic brain injury at autopsy. We measured apparent diffusion coefficients (ADCs), T1-weighted signal intensity ratios (SIRs) compared to vitreous humor and T2 relaxation times from 19 predefined brain areas typically involved in neonatal encephalopathy. There were no differences in mean ADC values, SIRs on T1-weighted images or T2 relaxation times in any of the 19 predefined brain areas between NE and SUND infants. All MRI images showed loss of cortical gray/white matter differentiation, loss of the normal high signal intensity (SI) in the posterior limb of the internal capsule on T1-weighted images, and high white matter SI on T2-weighted images. Normal post-mortem changes may be easily mistaken for ante-mortem ischemic injury, and current PM MRI quantitative assessment cannot reliably distinguish these. These findings may have important implications for appropriate interpretation of PM imaging findings, especially in medico-legal practice. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  4. Joint analysis of three-dimensional anatomical and functional data considering the cerebral post mortem imaging in rodents

    International Nuclear Information System (INIS)

    Dubois, Albertine

    2008-01-01

    The recent development of dedicated small animal anatomical (MRI) and functional (micro-PET) scanners has opened up the possibility of performing repeated functional in vivo studies in the same animal as the longitudinal follow-up of cerebral glucose metabolism. However, these systems still suffer technical limitations including a limited sensitivity and a reduced spatial resolution. Hence, autoradiography and histological studies remain the reference and widely used techniques for biological studies in small animals. The major disadvantage of these post mortem imaging techniques is that they require brain tissue sectioning, entailing the production of large numbers (up to several hundreds) of serial sections and the inherent loss of three-dimensional (3D) spatial consistency. The first step towards improving the analysis of this post mortem information was the development of reliable, automated procedures for the 3D reconstruction of the whole brain sections. We first developed an optimized data acquisition from large numbers of post mortem data (2D sections and block-face photographs). Then, we proposed different strategies of 3D reconstruction of the corresponding volumes. We also addressed the histological to autoradiographic sections and to block-face photographs co-registration problem (the photographic volume is intrinsically spatially consistent). These developments were essential for the 3D reconstruction but also enabled the evaluation of different methods of functional data analysis, from the most straightforward (manual delineation of regions of interest) to the most automated (Statistical Parametric Mapping-like approaches for group analysis). Two biological applications were carried out: visual stimulation in rats and cerebral metabolism in a transgenic mouse model of Alzheimer's disease. One perspective of this work is to match reconstructed post mortem data with in vivo images of the same animal. (author) [fr

  5. Towards muscle-specific meat color stability of Chinese Luxi yellow cattle: A proteomic insight into post-mortem storage.

    Science.gov (United States)

    Wu, Wei; Yu, Qian-Qian; Fu, Yu; Tian, Xiao-Jing; Jia, Fei; Li, Xing-Min; Dai, Rui-Tong

    2016-09-16

    Searching for potential predictors of meat color is a challenging task for the meat industry. In this study, the relationship between meat color parameters and the sarcoplasmic proteome of M. longissimuss lumborum (LL) and M. psoas major (PM) from Chinese Luxi yellow cattle during post-mortem storage (0, 5, 10 and 15days) were explored with the aid of the integrated proteomics and bioinformatics approaches. Meat color attributes revealed that LL displayed better color stability than PM during storage. Furthermore, sarcoplasmic proteins of these two muscles were compared between days 5, 10, 15 and day 0. Several proteins were closely correlated with meat color attributes and they were muscle-specific and responsible for the meat color stability at different storage periods. Glycerol-3-phosphate dehydrogenase, fructose-bisphosphate aldolase A isoform, glycogen phosphorylase, peroxiredoxin-2, phosphoglucomutase-1, superoxide dismutase [Cu-Zn], heat shock cognate protein (71kDa) might serve as the candidate predictors of meat color stability during post-mortem storage. In addition, bioinformatics analyses indicated that more proteins were involved in glycolytic metabolism of LL, which contributed to better meat color stability of LL than PM. The present results could provide a proteomic insight into muscle-specific meat color stability of Chinese Luxi yellow cattle during post-mortem storage. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Changes of microbial spoilage, lipid-protein oxidation and physicochemical properties during post mortem refrigerated storage of goat meat.

    Science.gov (United States)

    Sabow, Azad Behnan; Sazili, Awis Qurni; Aghwan, Zeiad Amjad; Zulkifli, Idrus; Goh, Yong Meng; Ab Kadir, Mohd Zainal Abidin; Nakyinsige, Khadijah; Kaka, Ubedullah; Adeyemi, Kazeem Dauda

    2016-06-01

    Examined was the effect of post mortem refrigerated storage on microbial spoilage, lipid-protein oxidation and physicochemical traits of goat meat. Seven Boer bucks were slaughtered, eviscerated and aged for 24 h. The Longissimus lumborum (LL) and Semitendinosus (ST) muscles were excised and subjected to 13 days post mortem refrigerated storage. The pH, lipid and protein oxidation, tenderness, color and drip loss were determined in LL while microbiological analysis was performed on ST. Bacterial counts generally increased with increasing aging time and the limit for fresh meat was reached at day 14 post mortem. Significant differences were observed in malondialdehyde (MDA) content at day 7 of storage. The thiol concentration significantly reduced as aging time increased. The band intensities of myosin heavy chain (MHC) and troponin-T significantly decreased as storage progressed, while actin remained relatively stable. After 14 days of aging, tenderness showed significant improvement while muscle pH and drip loss reduced with increase in storage time. Samples aged for 14 days had higher lightness (P goat meat. © 2016 Japanese Society of Animal Science.

  7. Usefulness of post mortem computed tomography versus conventional forensic autopsy of road accident victims (drivers and passengers).

    Science.gov (United States)

    Moskała, Artur; Woźniak, Krzysztof; Kluza, Piotr; Romaszko, Karol; Lopatin, Oleksiy

    2017-01-01

    Aim of the study: Deaths of in-vehicle victims (drivers and passengers) of road accidents represent a significant group of issues addressed by forensic medicine. Expressing opinions in this regard involves first of all the determination of the cause of death and the forensic pathologist's participation in the process of road accident reconstruction through defining the mechanism of bodily harm. The scope of the opinion as well as its accuracy and degree of detail largely depend on the scope of forensic autopsy. In this context, techniques that broaden the capabilities of standard autopsy are of particular importance. This paper compares the results of post mortem computed tomography (PMCT) of road accident victims (drivers and passengers) against the results of standard examination in order to determine the scope to which PMCT significantly enhances autopsy capabilities. Material and methods: The analysis covers 118 in-vehicle victims (drivers and passengers) examined from 2012 to 2014. In each case, post-mortem examination was preceded by PMCT examination using Somatom Emotion 16 (Siemens AG, Germany). Results: The results are presented in a tabular form. Conclusions: In most road accident victims (drivers and passengers), post mortem computed tomography significantly increases the results' degree of detail, particularly with regard to injuries of bones and gas collections.

  8. Laboratory experimental infection of sheep to Ornithobilharzia turkestanicum and its confirmation using post-mortem examination and histopathology

    Directory of Open Access Journals (Sweden)

    gholamreza karimi

    2014-11-01

    Full Text Available Ornithobilharzia turkestanicum from genus Ornithobilharzia genus and family Schistosomatidae is an important agent of parasitological infection in sheep. This parasite has been reported from Russia, China, Turkestan (Kazakhstan, Kyrgyzstan, Turkmenistan and Uzbekistan, Pakistan, Iraq, Turkey and Iran. Parasitological infection due to this agent could be one of the important factors of decreasing the production rate of livestock in Iran. The purpose of this study, was to experimentally infect sheep with this parasite and confirm the infection by post-mortem examination and Histopathology which was done successfully. Twenty five sheep were used in the study of which 10 sheep were experimentally infected by Ornithobilharzia turkestanikum using subcutaneous injection and 10 sheep by skin contact method and the other 5 sheep were kept as control. Result of post-mortem and Histopathology during a one year period confirmed that all of sheep were infected and adult worm, were seen in their mesentery. Mean number of cercaria used for inducing the infection was 6425 and 462 adult worms were collected post-mortem. There was no significant relationship between the number of cercaria and adult worms collected. Male sheep were more infected than female.

  9. The capability of high field MRI in demonstrating post-mortem fetal brains at different gestational age

    International Nuclear Information System (INIS)

    Zhang Zhonghe; Liu Shuwei; Lin Xiangtao; Gen Hequn; Teng Gaojun; Fang Fang; Zang Fengchao; Yu Taifei; Zhao Bin

    2009-01-01

    Objective: To study the capability of high field MRI in demonstrating the post-mortem fetal brains at different gestational age (GA). Methods: One hundred and eight post-mortem fetal brains of 14-40 weeks GA were evaluated by 3.0 T MRI. Eleven brains of 14 to 27 weeks GA with good 3.0 T MRI images were chosen and scanned by 7.0 T MRI. The developing sulci, layered structures of fetal cerebral cortex and basal nuclei were evaluated on MRI of different Tesla (3.0 T and 7.0 T) and their results analyzed. Results: On T 1 WI of 3.0 T MRI, the layered structures of fetal cerebral cortex were present at 14 weeks GA, the sulci were more accurately identified after 16 weeks GA. The basal nuclei were clearly distinguishable after 20 weeks CA, and these structures were better visualized as the GA increased. On T 2 WI of 7.0 T MRI, the sulci, layered structures of fetal cerebral cortex and basal nuclei were shown more clearly at the same GA when compared to 3.0 T, especially the sulci at the early developmental stages. Conclusions: T 1 WI of 3.0 T MRI could show the developing structures of post-mortem fetal brain well, but the T 2 WI of 7.0 T MRI were comparatively better. (authors)

  10. Automatic entry point planning for robotic post-mortem CT-based needle placement.

    Science.gov (United States)

    Ebert, Lars C; Fürst, Martin; Ptacek, Wolfgang; Ruder, Thomas D; Gascho, Dominic; Schweitzer, Wolf; Thali, Michael J; Flach, Patricia M

    2016-09-01

    Post-mortem computed tomography guided placement of co-axial introducer needles allows for the extraction of tissue and liquid samples for histological and toxicological analyses. Automation of this process can increase the accuracy and speed of the needle placement, thereby making it more feasible for routine examinations. To speed up the planning process and increase safety, we developed an algorithm that calculates an optimal entry point and end-effector orientation for a given target point, while taking constraints such as accessibility or bone collisions into account. The algorithm identifies the best entry point for needle trajectories in three steps. First, the source CT data is prepared and bone as well as surface data are extracted and optimized. All vertices of the generated surface polygon are considered to be potential entry points. Second, all surface points are tested for validity within the defined hard constraints (reachability, bone collision as well as collision with other needles) and removed if invalid. All remaining vertices are reachable entry points and are rated with respect to needle insertion angle. Third, the vertex with the highest rating is selected as the final entry point, and the best end-effector rotation is calculated to avoid collisions with the body and already set needles. In most cases, the algorithm is sufficiently fast with approximately 5-6 s per entry point. This is the case if there is no collision between the end-effector and the body. If the end-effector has to be rotated to avoid collision, calculation times can increase up to 24 s due to the inefficient collision detection used here. In conclusion, the algorithm allows for fast and facilitated trajectory planning in forensic imaging.

  11. Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study

    Science.gov (United States)

    Langkammer, Christian; Schweser, Ferdinand; Krebs, Nikolaus; Deistung, Andreas; Goessler, Walter; Scheurer, Eva; Sommer, Karsten; Reishofer, Gernot; Yen, Kathrin; Fazekas, Franz; Ropele, Stefan; Reichenbach, Jürgen R.

    2012-01-01

    Quantitative susceptibility mapping (QSM) is a novel technique which allows determining the bulk magnetic susceptibility distribution of tissue in vivo from gradient echo magnetic resonance phase images. It is commonly assumed that paramagnetic iron is the predominant source of susceptibility variations in gray matter as many studies have reported a reasonable correlation of magnetic susceptibility with brain iron concentrations in vivo. Instead of performing direct comparisons, however, all these studies used the putative iron concentrations reported in the hallmark study by Hallgren and Sourander (1958) for their analysis. Consequently, the extent to which QSM can serve to reliably assess brain iron levels is not yet fully clear. To provide such information we investigated the relation between bulk tissue magnetic susceptibility and brain iron concentration in unfixed (in situ) post mortem brains of 13 subjects using MRI and inductively coupled plasma mass spectrometry. A strong linear correlation between chemically determined iron concentration and bulk magnetic susceptibility was found in gray matter structures (r = 0.84, p < 0.001), whereas the correlation coefficient was much lower in white matter (r = 0.27, p < 0.001). The slope of the overall linear correlation was consistent with theoretical considerations of the magnetism of ferritin supporting that most of the iron in the brain is bound to ferritin proteins. In conclusion, iron is the dominant source of magnetic susceptibility in deep gray matter and can be assessed with QSM. In white matter regions the estimation of iron concentrations by QSM is less accurate and more complex because the counteracting contribution from diamagnetic myelinated neuronal fibers confounds the interpretation. PMID:22634862

  12. Performance of post-mortem CT compared to autopsy in children.

    Science.gov (United States)

    Krentz, Beatriz V; Alamo, Leonor; Grimm, Jochen; Dédouit, Fabrice; Bruguier, Christine; Chevallier, Christine; Egger, Coraline; Da Silva, Luiz F F; Grabherr, Silke

    2016-07-01

    Radiological techniques such as non-enhanced post-mortem computed tomography (PMCT) play an increasingly important role in death investigations, especially in cases of non-medicolegal context of death, where the consent of the next of kin is required to perform autopsy. Such consent is often difficult to obtain for deceased children, and radiological methods may be an acceptable alternative. The aim of our study was to evaluate the performance of PMCT explorations compared to medicolegal conventional autopsies in children and its potential usefulness in non-medicolegal situations. We retrospectively reviewed a group of 26 children aged 0-12 years who died of different causes, which were investigated by both conventional autopsy and PMCT. We compared the findings extracted from radiological and autopsy reports. All findings were grouped according to their importance with respect to cause of death and to the anatomical structure they covered: organs, vascular system, soft tissue, and skeletal system. A significantly larger number of findings were detected by autopsy compared to PMCT. Autopsy proved to be superior to PMCT, notably at detecting organ, soft tissue, and vascular findings, while PMCT was superior at detecting bone findings. However, no statistically significant differences were found between the methods concerning the essential findings used to define the cause of death. In children, PMCT was less sensitive than conventional autopsy for detecting general findings. However, most essential findings were detected by both methods. PMCT was superior to autopsy for the detection of bone lesions in children. Up to today, very rare literature exists concerning PMCT in children, especially in a forensic setting. This article investigates the advantages and limitations of PMCT compared to autopsy in a unique study group and discusses possibilities for future developments.

  13. SU-E-T-481: In Vivo and Post Mortem Animal Irradiation: Measured Vs. Calculated Doses

    Energy Technology Data Exchange (ETDEWEB)

    Heintz, P [Univ New Mexico Radiology Dept., Albuquerque, NM (United States); Heintz, B [Texas Oncology, PA, Southlake, TX (United States); Sandoval, D [University of New Mexico, Albuquerque, NM (United States); Weber, W; Melo, D; Guilmette, R [Lovelace Respiratory Research Institute, Albuquerque, NM (United States)

    2015-06-15

    Purpose: Computerized radiation therapy treatment planning is performed on almost all patients today. However it is seldom used for laboratory irradiations. The first objective is to assess whether modern radiation therapy treatment planning (RTP) systems accurately predict the subject dose by comparing in vivo and decedent dose measurements to calculated doses. The other objective is determine the importance of using a RTP system for laboratory irradiations. Methods: 5 MOSFET radiation dosimeters were placed enterically in each subject (2 sedated Rhesus Macaques) to measure the absorbed dose at 5 levels (carina, lung, heart, liver and rectum) during whole body irradiation. The subjects were treated with large opposed lateral fields and extended distances to cover the entire subject using a Varian 600C linac. CT simulation was performed ante-mortem (AM) and post-mortem (PM). To compare AM and PM doses, calculation points were placed at the location of each dosimeter in the treatment plan. The measured results were compared to the results using Varian Eclipse and Prowess Panther RTP systems. Results: The Varian and Prowess treatment planning system agreed to within in +1.5% for both subjects. However there were significant differences between the measured and calculated doses. For both animals the calculated central axis dose was higher than prescribed by 3–5%. This was caused in part by inaccurate measurement of animal thickness at the time of irradiation. For one subject the doses ranged from 4% to 7% high and the other subject the doses ranged 7% to 14% high when compared to the RTP doses. Conclusions: Our results suggest that using proper CT RTP system can more accurately deliver the prescribed dose to laboratory subjects. It also shows that there is significant dose variation in such subjects when inhomogeneities are not considered in the planning process.

  14. Skeletal abnormalities in fetuses with Down's syndrome: a radiographic post-mortem study

    International Nuclear Information System (INIS)

    Stempfle, N.; Brisse, H.; Huten, Y.; Fredouille, C.; Nessmann, C.

    1999-01-01

    Objective. To evaluate skeletal abnormalities on post-mortem radiographs of fetuses with Down's syndrome. Materials and methods. Biometrical and morphological criteria, which are used for US prenatal detection of trisomy 21, were assessed. Limb long bones, biparietal diameter (BPD)/occipito-frontal diameter (OFD) ratio, ossification of nasal bones and appearance of the middle phalanx of the fifth digit (P2) in 60 fetuses with Down's syndrome were analysed and compared with 82 normal fetuses matched for gestational age (GA) from 15 to 40 weeks' gestation (WG). Results. We observed reduced growth velocity of limb long bones during the third trimester in both groups, but the reduction was more pronounced in the trisomic group. Brachycephaly was found as early as 15 WG in Down's syndrome and continued throughout gestation (sensitivity 0.28, specificity 1). Ossification of the nasal bones, which can be detected in normal fetuses from 14 WG, was absent in one quarter of trisomic fetuses, regardless of GA. The middle phalanx of the fifth digit was evaluated by comparison with the distal phalanx (P3) of the same digit. We found that P2 was not ossified in 11/31 trisomic fetuses before 23 WG, and was either not ossified or hypoplastic in 17/29 cases after 24 WG (sensitivity 0.56, specificity 1). Conclusions. Three key skeletal signs were present in trisomic fetuses: brachycephaly, absence of nasal bone ossification, and hypoplasia of the middle phalanx of the fifth digit. All these signs are appropriate to prenatal US screening. When present, they fully justify determination of the fetal karyotype by amniocentesis. (orig.)

  15. Only connect: the merger of BMC Pharmacology and BMC Clinical Pharmacology.

    Science.gov (United States)

    Moylan, Elizabeth C; Morrey, Christopher; Appleford-Cook, Joanne M

    2012-08-13

    This editorial celebrates the launch of BMC Pharmacology and Toxicology within the BMC series of journals published by BioMed Central. The scope of the journal is interdisciplinary encompassing toxicology, experimental and clinical pharmacology including clinical trials. In this editorial we discuss the origins of this new journal and the ethos and policies under which it will operate.

  16. Radioimmunoassay in basic and clinical pharmacology

    International Nuclear Information System (INIS)

    Patrono, C.; Peskar, B.A.

    1987-01-01

    The subject of the book is the development, validation and application of radioimmunoassay (RIA) techniques for the measurement of a variety of substances in animal and human body fluids. The book discusses methodological and conceptual issues related to the main classes of mediators of drug action and to drugs themselves, as assayed by this particular analytical technique. A number of introductory chapters provide basic information concerning production and characterization of antibodies, labeling techniques, statistical aspects and validation criteria, insight into problems related to the development and validation of RIA for the newly discovered mediator(s). In the following chapters, the emphasis is placed on the technical details relevant to each class of compounds and on specific aspects of their applications to basic and/or clinical pharmacological studies. New developments in this area, such as monoclonal antibodies and non-radioactive labeling techniques, are also covered

  17. Clinical pharmacology of atovaquone and proguanil hydrochloride.

    Science.gov (United States)

    Beerahee, M

    1999-05-01

    Atovaquone and proguanil hydrochloride is a new antimalarial combination that is used for treatment and prophylaxis of malaria. The clinical pharmacology of atovaquone and proguanil was reviewed. Atovaquone is a highly lipophilic compound with low aqueous solubility, the absorption of which is limited by the rate and extent of dissolution. Dietary fat increases the rate and extent of atovaquone absorption, increasing AUC two- to threefold and C(max) fivefold over fasting. Proguanil is rapidly and extensively absorbed regardless of food intake. Atovaquone is highly protein bound (> 99%) but does not displace other highly protein bound drugs in vitro, indicating significant drug interactions arising from displacement are unlikely. Atovaquone is predominantly eliminated unchanged in feces, with negligible excretion in urine. Proguanil is partially metabolized and partially excreted unchanged in urine. Its principal metabolite, cycloguanil, is also excreted in urine. Metabolism of proguanil is mediated in the liver by the cytochrome P450 3A and 2C subfamilies. The elimination half-life of atovaquone is 2 to 3 days in adults and 1 to 2 days in children. The elimination half-lives of proguanil and cycloguanil are 12 to 15 hours in adults and children. Dosage adjustments based on body weight categories in children (1/4 dose for 11-20 kg, 1/2 dose for > 20-30 kg, 3/4 dose for > 30-40 kg, and full dose for > 40 kg) achieve plasma concentrations that are safe and effective during prophylaxis and treatment of malaria. No dose adjustments for race, proguanil metabolizer status, gender, or elderly patients are needed, or for patients with mild to moderately impaired renal or hepatic function. The clinical pharmacology of atovaquone and proguanil provides a rationale for the dosing regimens recommended for treatment and prophylaxis of malaria.

  18. Post mortem investigations of the NPP Greifswald WWER-440 reactor pressure vessels

    Energy Technology Data Exchange (ETDEWEB)

    Schuhknecht, Jan; Viehrig, Hans-Werner; Weiss, Frank-Peter; Rindelhardt, Udo [Forschungszentrum Dresden-Rossendorf e.V., Dresden (Germany). Inst. for Safety Research; Keller, Werner [Studsvik GmbH und Co. KG, Stutensee (Germany)

    2008-07-01

    The paper presents first results of the post mortem investigations performed at the reactor pressure vessels (RPV) of the Russian WWER-440 type reactors. Trepans were taken from the core weld SN0.1.4 and base metal of the unit 1 RPV. This RPV was annealed after 15 years of operation and operated for two more years. At first the trepan of the core welding seam was investigated by Master Curve (MC) testing. Specimens from 5 locations through the thickness of the welding seam were tested according to ASTM E1921-05. The reference temperature T{sub 0} was calculated with the measured fracture toughness values, K{sub Jc}, at brittle failure of the specimen. Generally the K{sub Jc} values measured on pre-cracked and side-grooved Charpy size SE(B) specimens of the investigated weld metal follow the course of the Master Curve. The K{sub Jc} values show a remarkable scatter. More values than expected lie below the 5% fractile. In addition the MC SINTAP procedure was applied to determine T{sub 0}{sup SINTAP} of the brittle fraction of the data set. There are remarkable differences between T{sub 0} and T{sub 0}{sup SINTAP} indicating macroscopic inhomogeneous weld metal. The highest T{sub 0} was about 50 C at a distance of 22 mm from the inner surface of the weld. It is 40 K higher compared with T{sub 0} at the inner surface. This is important for the assessment of ductile-to-brittle temperatures measured with sub size Charpy specimens made of weld metal from the inner RPV wall. This material may not represent the most conservative condition. The results presented in this paper show that the Master Curve approach as adopted in the test standard ASTM E1921-05 is applicable to the investigated WWER-440 multilayer weld metal. The results are of direct importance for an advanced WWER-440 RPV integrity assessment. On the other hand the data pool is broadened for a general introduction of the MC based RPV integrity assessment in the national codes. Furthermore general experiences in

  19. Compressive rib fracture: peri-mortem and post-mortem trauma patterns in a pig model.

    Science.gov (United States)

    Kieser, Jules A; Weller, Sarah; Swain, Michael V; Neil Waddell, J; Das, Raj

    2013-07-01

    Despite numerous studies on high impact fractures of ribs, little is known about compressive rib injuries. We studied rib fractures from a biomechanical and morphological perspective using 15, 5th ribs of domestic pigs Sus scrofa, divided into two groups, desiccated (representing post-mortem trauma) and fresh ribs with intact periosteum (representing peri-mortem trauma). Ribs were axially compressed and subjected to four-point bending in an Instron 3339 fitted with custom jigs. Morphoscopic analysis of resultant fractures consisted of standard optical methods, micro-CT (μCT) and scanning electron microscopy (SEM). During axial compression, fresh ribs had slightly higher strength because of energy absorption capabilities of their soft and fluidic components. In flexure tests, dry ribs showed typical elastic-brittle behaviour with long linear load-extension curves, followed by relatively short non-linear elastic (hyperelastic) behaviour and brittle fracture. Fresh ribs showed initial linear-elastic behaviour, followed by strain softening, visco-plastic responses. During the course of loading, dry bone showed minimal observable damage prior to the onset of unstable fracture. In contrast, fresh bone showed buckling-like damage features on the compressive surface and cracking parallel to the axis of the bone. Morphologically, all dry ribs fractured precipitously, whereas all but one of the fresh ribs showed incomplete fracture. The mode of fracture, however, was remarkably similar for both groups, with butterfly fractures predominating (7/15, 46.6% dry and wet). Our study highlights the fact that under controlled loading, despite seemingly similar butterfly fracture morphology, fresh ribs (representing perimortem trauma) show a non-catastrophic response. While extensive strain softening observed for the fresh bone does show some additional micro-cracking damage, it appears that the periosteum may play a key role in imparting the observed pseudo-ductility to the ribs

  20. Post mortem investigations of the NPP Greifswald WWER-440 reactor pressure vessels

    International Nuclear Information System (INIS)

    Schuhknecht, Jan; Viehrig, Hans-Werner; Weiss, Frank-Peter; Rindelhardt, Udo

    2008-01-01

    The paper presents first results of the post mortem investigations performed at the reactor pressure vessels (RPV) of the Russian WWER-440 type reactors. Trepans were taken from the core weld SN0.1.4 and base metal of the unit 1 RPV. This RPV was annealed after 15 years of operation and operated for two more years. At first the trepan of the core welding seam was investigated by Master Curve (MC) testing. Specimens from 5 locations through the thickness of the welding seam were tested according to ASTM E1921-05. The reference temperature T 0 was calculated with the measured fracture toughness values, K Jc , at brittle failure of the specimen. Generally the K Jc values measured on pre-cracked and side-grooved Charpy size SE(B) specimens of the investigated weld metal follow the course of the Master Curve. The K Jc values show a remarkable scatter. More values than expected lie below the 5% fractile. In addition the MC SINTAP procedure was applied to determine T 0 SINTAP of the brittle fraction of the data set. There are remarkable differences between T 0 and T 0 SINTAP indicating macroscopic inhomogeneous weld metal. The highest T 0 was about 50 C at a distance of 22 mm from the inner surface of the weld. It is 40 K higher compared with T 0 at the inner surface. This is important for the assessment of ductile-to-brittle temperatures measured with sub size Charpy specimens made of weld metal from the inner RPV wall. This material may not represent the most conservative condition. The results presented in this paper show that the Master Curve approach as adopted in the test standard ASTM E1921-05 is applicable to the investigated WWER-440 multilayer weld metal. The results are of direct importance for an advanced WWER-440 RPV integrity assessment. On the other hand the data pool is broadened for a general introduction of the MC based RPV integrity assessment in the national codes. Furthermore general experiences in the cutting of irradiated RPV steels are collected

  1. Comparing different post-mortem human samples as DNA sources for downstream genotyping and identification.

    Science.gov (United States)

    Calacal, Gayvelline C; Apaga, Dame Loveliness T; Salvador, Jazelyn M; Jimenez, Joseph Andrew D; Lagat, Ludivino J; Villacorta, Renato Pio F; Lim, Maria Cecilia F; Fortun, Raquel D R; Datar, Francisco A; De Ungria, Maria Corazon A

    2015-11-01

    The capability of DNA laboratories to perform genotyping procedures from post-mortem remains, including those that had undergone putrefaction, continues to be a challenge in the Philippines, a country characterized by very humid and warm conditions all year round. These environmental conditions accelerate the decomposition of human remains that were recovered after a disaster and those that were left abandoned after a crime. When considerable tissue decomposition of human remains has taken place, there is no other option but to extract DNA from bone and/or teeth samples. Routinely, femur shafts are obtained from recovered bodies for human identification because the calcium matrix protects the DNA contained in the osteocytes. In the Philippines, there is difficulty in collecting femur samples after natural disasters or even human-made disasters, because these events are usually characterized by a large number of fatalities. Identification of casualties is further delayed by limitation in human and material resources. Hence, it is imperative to test other types of biological samples that are easier to collect, transport, process and store. We analyzed DNA that were obtained from body fluid, bone marrow, muscle tissue, clavicle, femur, metatarsal, patella, rib and vertebral samples from five recently deceased untreated male cadavers and seven male human remains that were embalmed, buried for ∼ 1 month and then exhumed. The bodies had undergone different environmental conditions and were in various stages of putrefaction. A DNA extraction method utilizing a detergent-washing step followed by an organic procedure was used. The utility of bone marrow and vitreous fluid including bone marrow and vitreous fluid that was transferred on FTA(®) cards and subjected to autosomal STR and Y-STR DNA typing were also evaluated. DNA yield was measured and the presence or absence of PCR inhibitors in DNA extracts was assessed using Plexor(®)HY. All samples were amplified using

  2. Human decomposition and the reliability of a 'Universal' model for post mortem interval estimations.

    Science.gov (United States)

    Cockle, Diane L; Bell, Lynne S

    2015-08-01

    Human decomposition is a complex biological process driven by an array of variables which are not clearly understood. The medico-legal community have long been searching for a reliable method to establish the post-mortem interval (PMI) for those whose deaths have either been hidden, or gone un-noticed. To date, attempts to develop a PMI estimation method based on the state of the body either at the scene or at autopsy have been unsuccessful. One recent study has proposed that two simple formulae, based on the level of decomposition humidity and temperature, could be used to accurately calculate the PMI for bodies outside, on or under the surface worldwide. This study attempted to validate 'Formula I' [1] (for bodies on the surface) using 42 Canadian cases with known PMIs. The results indicated that bodies exposed to warm temperatures consistently overestimated the known PMI by a large and inconsistent margin for Formula I estimations. And for bodies exposed to cold and freezing temperatures (less than 4°C), then the PMI was dramatically under estimated. The ability of 'Formulae II' to estimate the PMI for buried bodies was also examined using a set of 22 known Canadian burial cases. As these cases used in this study are retrospective, some of the data needed for Formula II was not available. The 4.6 value used in Formula II to represent the standard ratio of time that burial decelerates the rate of decomposition was examined. The average time taken to achieve each stage of decomposition both on, and under the surface was compared for the 118 known cases. It was found that the rate of decomposition was not consistent throughout all stages of decomposition. The rates of autolysis above and below the ground were equivalent with the buried cases staying in a state of putrefaction for a prolonged period of time. It is suggested that differences in temperature extremes and humidity levels between geographic regions may make it impractical to apply formulas developed in

  3. Microstructural analysis of geopolymer developed from wood fly ash, post-mortem doloma refractory and metakaolin; Analise microestrutural de geopolimero desenvolvido a partir de cinza de olaria, tijolo refratario dolomitico post-mortem e metacaulim

    Energy Technology Data Exchange (ETDEWEB)

    Moura, Jailes de Santana; Mafra, Marcio Paulo de Araujo; Rabelo, Adriano Alves; Fagury, Renata Lilian Ribeiro Portugal; Fagury Neto, Elias, E-mail: jailesmoura@hotmail.com, E-mail: fagury@unifesspa.edu.br [Universidade Federal do Sul e Sudeste do Para (UNIFESSPA), PA (Brazil). Faculdade de Engenharia de Materiais

    2016-07-01

    Geopolymers are one of the widely discussed topics of materials science in recent times due to its vast potential as an alternative binder material to cement. This work aimed to evaluate the microstructure of geopolymers developed from wood fly ash, post-mortem doloma refractory and metakaolin. A preliminary study has been completed and achieved significant results compressive strength: the best formulation of geopolymer paste obtained approximately 25 MPa. Microstructural analysis by scanning electron microscopy, the geopolymer paste, allowed to verify the homogeneity, distribution of components, and providing evidence of raw materials that do not respond if there was crystalline phase, porosity and density of the structure. (author)

  4. Efeito do resfriamento sobre a textura post-mortem da carne do peixe matrinxã Brycon cephalus Chilling effect on the post-mortem texture of the matrinxã fish muscle Brycon cephalus

    Directory of Open Access Journals (Sweden)

    H. Suárez-Mahecha

    2007-08-01

    Full Text Available Os mecanismos que causam o amolecimento e a perda na textura post-mortem da carne de matrinxã foram determinados por meio das mudanças na microestrutura do músculo, imediatamente após a morte e depois de 12 horas de estocagem a -3°C. As observações na microestrutura, realizadas com microscópio eletrônico de transmissão, foram semelhantes aos resultados obtidos na força de ruptura do músculo medidos com o texturômetro. Os valores da força da ruptura foram menores para a carne após o resfriamento. Observou-se que as fibras do colágeno do tecido conectivo pericelular se desintegraram e que as do colágeno do tecido conectivo do miocommata conservaram sua arquitetura e integridade. Houve pouca degradação da linha Z. Isso sugere que o amolecimento post-mortem da carne de mantrinxã, durante a estocagem a -3°C, é causado pela degradação do tecido conectivo pericelular.In order to determine the mechanisms that cause the post mortem muscle softness of the matrinxã Brycon cephalus, changes in the micro structure of the muscle were observed immediately after death and after 12 hours of storage at -3º C, measuring the firmness of the flesh with test instruments. Observations by the transmission electron microscope were similar to the results obtained in the breaking strength of the muscle measured with a texturometer. The values of the breaking strength of the fish muscle were smaller after chilling. At the same time, it was observed that the collagen fibers of the pericellular connective tissue had disintegrated, while the collagen fibers of the miocommata connective tissue maintained their organization and integrity. No evident breakdown of Z-discs was observed. It is suggested that the post-mortem tenderization of the matrinxã muscle during chilled storage was due to the disintegration of the collagen fibers in the pericellular connective tissue and, in a smaller extent, to the weakening of Z-disk.

  5. Post-mortem magnetic resonance foetal imaging: a study of morphological correlation with conventional autopsy and histopathological findings.

    Science.gov (United States)

    Vullo, Annamaria; Panebianco, Valeria; Cannavale, Giuseppe; Aromatario, Mariarosaria; Cipolloni, Luigi; Frati, Paola; Santurro, Alessandro; Vullo, Francesco; Catalano, Carlo; Fineschi, Vittorio

    2016-11-01

    The aim of the present study is to offer our experience concerning post-mortem magnetic resonance (PMMR) in foetal death cases and an evaluation of the differences between the findings acquired by PMMR and by forensic autopsy. Fifteen foetuses were recruited from July 2014 to December 2015. These had suffered intrauterine death in women in the 21st to 38th week of gestation who were treated in the emergency department for non-perception of foetal movements. We performed a PMMR on foetuses, 3 ± 1 days on average from the time of death, and then a complete forensic autopsy was performed. All 15 foetuses were examined with a whole-body study protocol, starting from the skull, down to and including the lower limbs. The total time of examination ranged from 20 to 30 min in each case. The external evaluation and description of post-mortem phenomena (maceration), record of the weight and detection and the various measurements of foetal diameters were evaluated before performing autopsy. A complete histopathological study was performed in each case. Out of 15 cases examined, eight were negative for structural anatomical abnormalities and/or diseases, both in the preliminary radiological examination and the traditional autopsy. In the remaining seven cases, pathological findings were detected by PMMR with corresponding results at autopsy. PMMR can provide useful information on foetal medical conditions and result in improved diagnostic classification. It may enable the planning of a more suitable technique before proceeding to autopsy, including focusing on certain aspects of organ pathology otherwise not detectable. The association between PMMR, post-mortem examination and related histological study of the foetus-placenta unit could help reduce the percentage of cases in which the cause of foetal death remains unexplained. Lastly, it may allow a selective sampling of the organ in order to target histological investigations.

  6. Severe malaria - a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report

    Directory of Open Access Journals (Sweden)

    Adem Patricia

    2010-01-01

    Full Text Available Abstract Background Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here. Case presentation A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a post-mortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent. Conclusions The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further

  7. Differential Nuclear and Mitochondrial DNA Preservation in Post-Mortem Teeth with Implications for Forensic and Ancient DNA Studies

    Science.gov (United States)

    Higgins, Denice; Rohrlach, Adam B.; Kaidonis, John; Townsend, Grant; Austin, Jeremy J.

    2015-01-01

    Major advances in genetic analysis of skeletal remains have been made over the last decade, primarily due to improvements in post-DNA-extraction techniques. Despite this, a key challenge for DNA analysis of skeletal remains is the limited yield of DNA recovered from these poorly preserved samples. Enhanced DNA recovery by improved sampling and extraction techniques would allow further advancements. However, little is known about the post-mortem kinetics of DNA degradation and whether the rate of degradation varies between nuclear and mitochondrial DNA or across different skeletal tissues. This knowledge, along with information regarding ante-mortem DNA distribution within skeletal elements, would inform sampling protocols facilitating development of improved extraction processes. Here we present a combined genetic and histological examination of DNA content and rates of DNA degradation in the different tooth tissues of 150 human molars over short-medium post-mortem intervals. DNA was extracted from coronal dentine, root dentine, cementum and pulp of 114 teeth via a silica column method and the remaining 36 teeth were examined histologically. Real time quantification assays based on two nuclear DNA fragments (67 bp and 156 bp) and one mitochondrial DNA fragment (77 bp) showed nuclear and mitochondrial DNA degraded exponentially, but at different rates, depending on post-mortem interval and soil temperature. In contrast to previous studies, we identified differential survival of nuclear and mtDNA in different tooth tissues. Futhermore histological examination showed pulp and dentine were rapidly affected by loss of structural integrity, and pulp was completely destroyed in a relatively short time period. Conversely, cementum showed little structural change over the same time period. Finally, we confirm that targeted sampling of cementum from teeth buried for up to 16 months can provide a reliable source of nuclear DNA for STR-based genotyping using standard

  8. Prevalence of Atherosclerotic Coronary Stenosis in Asymptomatic North Indian Population: A Post-mortem Coronary Angiography Study.

    Science.gov (United States)

    Bansal, Yogender Singh; Mandal, Shatrugan Prasad; Kumar, Senthil; Setia, Puneet

    2015-09-01

    A preliminary study of coronaries using post-mortem angiography was undertaken to see the prevalence of atherosclerotic coronary stenosis in non-cardiac unnatural deaths. This study was conducted in a tertiary care centre located in Chandigarh. A total of 128 medico-legal cases were studied comprising 88 males and 40 females. Post-mortem examinations of these MLC cases were conducted in the Department of Forensic Medicine, PGIMER, Chandigarh. All hearts were visually screened by post-mortem coronary angiography first and then grossly examined using serial transverse incision technique in positive screening cases to find the degree of narrowing. Of the study group, 34% males and 20% females showed evidence of narrowing on angiography. Of the males showing coronary stenosis, 83% had single vessel disease and 13% had double vessel disease, while only one individual had triple vessel disease. In cases of female, all the cases of coronary stenosis were single vessel disease. Left anterior descending coronary artery (LAD) was the most common vessel involved, followed by right coronary artery (RCA) & Left circumflex artery (LCX) and in cases of double vessel disease, LAD in combination with LCX was responsible for 75% of the cases. Remarkably 23.6% of study population in the age group of less than 40 years showed appreciable narrowing in at least one of the coronaries. In general, the prevalence of CAD is on the rise, particularly in younger population owing to the changes in their lifestyle and food habits. This preliminary study revealed evidence of narrowing of at least one coronary in 34% male and 20% female population and 23.6% subjects were less than 40 years old. Further detailed studies are needed especially in younger age group and to support the need for preventive cardiology in the early years of life.

  9. Hippocampal Microbleed on a Post-Mortem T2*-Weighted Gradient-Echo 7.0-Tesla Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    J. De Reuck

    2011-09-01

    Full Text Available The present post-mortem study of a brain from an Alzheimer patient showed on a T2*-weighted gradient-echo 7.0-T MRI of a coronal brain section a hyposignal in the hippocampus, suggesting a microbleed. On the corresponding histological examination, only iron deposits around the granular cellular layer and in blood vessel walls of the hippocampus were observed without evidence of a bleeding. This case report illustrates that the detection of microbleeds on MRI has to be interpreted with caution.

  10. Post-mortem assessment of hypoperfusion of cerebral cortex in Alzheimer's disease and vascular dementia.

    Science.gov (United States)

    Thomas, Taya; Miners, Scott; Love, Seth

    2015-04-01

    Perfusion is reduced in the cerebral neocortex in Alzheimer's disease. We have explored some of the mechanisms, by measurement of perfusion-sensitive and disease-related proteins in post-mortem tissue from Alzheimer's disease, vascular dementia and age-matched control brains. To distinguish physiological from pathological reduction in perfusion (i.e. reduction exceeding the decline in metabolic demand), we measured the concentration of vascular endothelial growth factor (VEGF), a protein induced under conditions of tissue hypoxia through the actions of hypoxia-inducible factors, and the myelin associated glycoprotein to proteolipid protein 1 (MAG:PLP1) ratio, which declines in chronically hypoperfused brain tissue. To evaluate possible mechanisms of hypoperfusion, we also measured the levels of amyloid-β40, amyloid-β42, von Willebrand factor (VWF; a measure of microvascular density) and the potent vasoconstrictor endothelin 1 (EDN1); we assayed the activity of angiotensin I converting enzyme (ACE), which catalyses the production of another potent vasoconstrictor, angiotensin II; and we scored the severity of arteriolosclerotic small vessel disease and cerebral amyloid angiopathy, and determined the Braak tangle stage. VEGF was markedly increased in frontal and parahippocampal cortex in Alzheimer's disease but only slightly and not significantly in vascular dementia. In frontal cortex the MAG:PLP1 ratio was significantly reduced in Alzheimer's disease and even more so in vascular dementia. VEGF but not MAG:PLP1 increased with Alzheimer's disease severity, as measured by Braak tangle stage, and correlated with amyloid-β42 and amyloid-β42: amyloid-β40 but not amyloid-β40. Although MAG:PLP1 tended to be lowest in cortex from patients with severe small vessel disease or cerebral amyloid angiopathy, neither VEGF nor MAG:PLP1 correlated significantly with the severity of structural vascular pathology (small vessel disease, cerebral amyloid angiopathy or VWF

  11. Clinical pharmacology in Russia-historical development and current state.

    Science.gov (United States)

    Zagorodnikova Goryachkina, Ksenia; Burbello, Aleksandra; Sychev, Dmitry; Frolov, Maxim; Kukes, Vladimir; Petrov, Vladimir

    2015-02-01

    Clinical pharmacology in Russia has long history and is currently active, but rather unrecognized internationally. It is governmentally approved as a teaching/scientific specialty since 1983 and as a medical specialty since 1997. Courses of clinical pharmacology are included in the undergraduate curricula in the 5th and/or 6th year of education at all medical schools in the Russian Federation. Postgraduate education includes initial specialization in internal medicine with further residency in clinical pharmacology. Governmental legislation recommends that every healthcare institution has either a department or a single position of clinical pharmacologist. Major routine duties include information about and monitoring of medication use, consultations in difficult clinical situations, pharmacogenetic counseling, therapeutic drug monitoring, pharmacovigilance, and participation in drug and therapeutics (formulary) committees. There are official experts in clinical pharmacology in Russia responsible for coordinating relevant legislative issues. The chief expert clinical pharmacologist represents the discipline directly at the Ministry of Health. Research in clinical pharmacology in Russia is extensive and variable, but only some of it is published internationally. Russia is a participant of international societies of clinical pharmacology and therapeutics and collaboration is actively ongoing. There are still certain problems related to the development of the discipline in Russia-some healthcare institutions do not see the need for clinical pharmacology. However, the number of clinical pharmacologists in Russia is increasing as well as their role in physicians' education, national healthcare, and research.

  12. Post mortem rigor development in the Egyptian goose (Alopochen aegyptiacus) breast muscle (pectoralis): factors which may affect the tenderness.

    Science.gov (United States)

    Geldenhuys, Greta; Muller, Nina; Frylinck, Lorinda; Hoffman, Louwrens C

    2016-01-15

    Baseline research on the toughness of Egyptian goose meat is required. This study therefore investigates the post mortem pH and temperature decline (15 min-4 h 15 min post mortem) in the pectoralis muscle (breast portion) of this gamebird species. It also explores the enzyme activity of the Ca(2+)-dependent protease (calpain system) and the lysosomal cathepsins during the rigor mortis period. No differences were found for any of the variables between genders. The pH decline in the pectoralis muscle occurs quite rapidly (c = -0.806; ultimate pH ∼ 5.86) compared with other species and it is speculated that the high rigor temperature (>20 °C) may contribute to the increased toughness. No calpain I was found in Egyptian goose meat and the µ/m-calpain activity remained constant during the rigor period, while a decrease in calpastatin activity was observed. The cathepsin B, B & L and H activity increased over the rigor period. Further research into the connective tissue content and myofibrillar breakdown during aging is required in order to know if the proteolytic enzymes do in actual fact contribute to tenderisation. © 2015 Society of Chemical Industry.

  13. Ethical considerations in forensic genetics research on tissue samples collected post-mortem in Cape Town, South Africa.

    Science.gov (United States)

    Heathfield, Laura J; Maistry, Sairita; Martin, Lorna J; Ramesar, Raj; de Vries, Jantina

    2017-11-29

    The use of tissue collected at a forensic post-mortem for forensic genetics research purposes remains of ethical concern as the process involves obtaining informed consent from grieving family members. Two forensic genetics research studies using tissue collected from a forensic post-mortem were recently initiated at our institution and were the first of their kind to be conducted in Cape Town, South Africa. This article discusses some of the ethical challenges that were encountered in these research projects. Among these challenges was the adaptation of research workflows to fit in with an exceptionally busy service delivery that is operating with limited resources. Whilst seeking guidance from the literature regarding research on deceased populations, it was noted that next of kin of decedents are not formally recognised as a vulnerable group in the existing ethical and legal frameworks in South Africa. The authors recommend that research in the forensic mortuary setting is approached using guidance for vulnerable groups, and the benefit to risk standard needs to be strongly justified. Lastly, when planning forensic genetics research, consideration must be given to the potential of uncovering incidental findings, funding to validate these findings and the feedback of results to family members; the latter of which is recommended to occur through a genetic counsellor. It is hoped that these experiences will contribute towards a formal framework for conducting forensic genetic research in medico-legal mortuaries in South Africa.

  14. The importance of post-mortem computed tomography (PMCT) in confrontation with conventional forensic autopsy of victims of motorcycle accidents.

    Science.gov (United States)

    Moskała, Artur; Woźniak, Krzysztof; Kluza, Piotr; Romaszko, Karol; Lopatin, Oleksij

    2016-01-01

    Since traffic accidents are an important problem in forensic medicine, there is a constant search for new solutions to help with an investigation process in such cases. In recent years there was a rapid development of post-mortem imaging techniques, especially post-mortem computed tomography (PMCT). In our work we concentrated on a potential advantage of PMCT in cases of motorcycle accident fatalities. The results of forensic autopsy were compared with combined results of the autopsy and PMCT to check in which areas use of these two techniques gives statistically important increase in number of findings. The hypothesis was confirmed in case of pneumothorax and fractures of skull, spine, clavicle, scapula, lower leg bones. As for majority of other bone fractures locations and brain injures there were single cases with pathologies visible only in PMCT, but too few to reach expected level of p-value. In case of injuries of solid organs and soft tissues statistical analysis did not confirmed any advantage of unenhanced PMCT use. On the whole it has been shown that PMCT used as an adjunct to forensic autopsy can cause an increase in information about vitally important regions in case of motorcycle accident fatalities. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Post-mortem hemoparasite detection in free-living Brazilian brown brocket deer (Mazama gouazoubira, Fischer 1814).

    Science.gov (United States)

    Silveira, Júlia Angélica Gonçalves da; Rabelo, Elida Mara Leite; Lima, Paula Cristina Senra; Chaves, Bárbara Neves; Ribeiro, Múcio Flávio Barbosa

    2014-01-01

    Tick-borne infections can result in serious health problems for wild ruminants, and some of these infectious agents can be considered zoonosis. The aim of the present study was the post-mortem detection of hemoparasites in free-living Mazama gouazoubira from Minas Gerais state, Brazil. The deer samples consisted of free-living M. gouazoubira (n = 9) individuals that died after capture. Necropsy examinations of the carcasses were performed to search for macroscopic alterations. Organ samples were collected for subsequent imprint slides, and nested PCR assays were performed to detect hemoparasite species. Imprint slide assays from four deer showed erythrocytes infected with Piroplasmida small trophozoites, and A. marginale corpuscles were observed in erythrocytes from two animals. A. marginale and trophozoite co-infections occurred in two deer. A nested PCR analysis of the organs showed that six of the nine samples were positive for Theileria sp., five were positive for A. phagocytophilum and three were positive for A. marginale, with co-infection occurring in four deer. The results of the present study demonstrate that post-mortem diagnostics using imprint slides and molecular assays are an effective method for detecting hemoparasites in organs.

  16. Pharmacological Activity and Clinical Use of PDRN

    Directory of Open Access Journals (Sweden)

    Francesco Squadrito

    2017-04-01

    Full Text Available PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout or Oncorhynchus keta (Chum Salmon sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects.

  17. Pharmacological Activity and Clinical Use of PDRN

    Science.gov (United States)

    Squadrito, Francesco; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Minutoli, Letteria; Altavilla, Domenica

    2017-01-01

    PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects. PMID:28491036

  18. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  19. Back to the Future - Part 2. Post-mortem assessment and evolutionary role of the bio-medicolegal sciences.

    Science.gov (United States)

    Ferrara, Santo Davide; Cecchetto, Giovanni; Cecchi, Rossana; Favretto, Donata; Grabherr, Silke; Ishikawa, Takaki; Kondo, Toshikazu; Montisci, Massimo; Pfeiffer, Heidi; Bonati, Maurizio Rippa; Shokry, Dina; Vennemann, Marielle; Bajanowski, Thomas

    2017-07-01

    Part 2 of the review "Back to the Future" is dedicated to the evolutionary role of the bio-medicolegal sciences, reporting the historical profiles, the state of the art, and prospects for future development of the main related techniques and methods of the ancillary disciplines that have risen to the role of "autonomous" sciences, namely, Genetics and Genomics, Toxicology, Radiology, and Imaging, involved in historic synergy in the "post-mortem assessment," together with the mother discipline Legal Medicine, by way of its primary fundament, universally denominated as Forensic Pathology. The evolution of the scientific research and the increased accuracy of the various disciplines will be oriented towards the elaboration of an "algorithm," able to weigh the value of "evidence" placed at the disposal of the "justice system" as real truth and proof.

  20. Preliminary approach on early post mortem stress and quality indexes changes in large size bluefin tuna (Thunnus thynnus

    Directory of Open Access Journals (Sweden)

    R. Ugolini

    2010-01-01

    Full Text Available Bluefin tuna (Thunnus thynnus is very appreciated on Japan and USA market for the preparation of sushi and sahimi. The market price of the fresh product can vary from 8 to 33 Euro/kg (gate farm/producers prices according to size, shape, fat level, meat colour, consistency and freshness (absence of “hyake”, all parameters strictly connected to feeding quality and quantity, rearing and killing stress factors and refrigeration times and conditions after death. Excessive levels of stress during the slaughtering can affect meat quality, contributing to significantly decrease of tuna’s price. The present trial was carried out to evaluate the possible harvesting/slaughtering stress effect on reared bluefin tuna meat quality, starting from the examination of the most important stress and quality parameters changes during the early post mortem period.

  1. Rapid determination of quetiapine in blood by gas chromatography-mass spectrometry. Application to post-mortem cases.

    Science.gov (United States)

    López-Guarnido, Olga; Tabernero, María Jesús; Hernández, Antonio F; Rodrigo, Lourdes; Bermejo, Ana M

    2014-10-01

    A simple, fast and sensitive method for the determination of quetiapine in human blood has been developed and validated. The method involved a basic liquid-liquid extraction procedure and subsequent analysis by gas chromatography-mass spectrometry, previous derivatization with bis(trimethylsilyl)-trifluoro-acetamide and chorotrimethylsilane (99 : 1). The methods of validation included linearity with a correlation coefficient > 0.99 over the range 0.02-1 µg ml(-1), intra- and interday precision (always < 12%) and accuracy (mean relative error always < 12%) to meet the bioanalytical acceptance criteria. The limit of detection was 0.005 µg ml(-1). The procedure was further applied to post mortems from the Institute of Legal Medicine, University of Santiago de Compostela. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Overview of JET post-mortem results following the 2007-9 operational period, and comparisons with previous campaigns

    International Nuclear Information System (INIS)

    Coad, J P; Gruenhagen, S; Widdowson, A; Hole, D E; Hakola, A; Koivuranta, S; Likonen, J; Rubel, M

    2011-01-01

    In 2010, all the plasma-facing components were removed from JET so that the carbon-based surfaces could be replaced with beryllium (Be) or tungsten as part of the ITER-like wall (ILW) project. This gives unprecedented opportunities for post-mortem analyses of these plasma-facing surfaces; this paper reviews the data obtained so far and relates the information to studies of tiles removed during previous JET shutdowns. The general pattern of erosion/deposition at the JET divertor has been maintained, with deposition of impurities in the scrape-off layer (SOL) at the inner divertor and preferential removal of carbon and transport into the corner. However, the remaining films in the SOL contain very high Be/C ratios at the surface. The first measurements of erosion using a tile profiler have been completed, with up to 200 microns erosion being recorded at points on the inner wall guard limiters.

  3. Post mortem concentrations of endogenous gamma hydroxybutyric acid (GHB) and in vitro formation in stored blood and urine samples.

    Science.gov (United States)

    Busardò, Francesco Paolo; Bertol, Elisabetta; Vaiano, Fabio; Baglio, Giovanni; Montana, Angelo; Barbera, Nunziata; Zaami, Simona; Romano, Guido

    2014-10-01

    Gamma-hydroxybutyrate (GHB) is a central nervous system depressant, primarily used as a recreational drug of abuse with numerous names. It has also been involved in various instances of drug-facilitated sexual assault due to its potential incapacitating effects. The first aim of this paper is to measure the post-mortem concentration of endogenous GHB in whole blood and urine samples of 30 GHB free-users, who have been divided according to the post-mortem interval (PMI) in three groups (first group: 24-36h; second group: 37-72h; third group: 73-192h), trying to evaluate the role of PMI in affecting post mortem levels. Second, the Authors have evaluated the new formation of GHB in vitro in blood and urine samples of the three groups, which have been stored at -20°C, 4°C and 20°C over a period of one month. The concentrations were measured by GC-MS after liquid-liquid extraction according to the method validated and published by Elliot (For. Sci. Int., 2003). For urine samples, GHB concentrations were creatinine-normalized. In the first group the GHB mean concentration measured after autopsy was: 2.14mg/L (range 0.54-3.21mg/L) in blood and 3.90mg/g (range 0.60-4.81mg/g) in urine; in the second group it was: 5.13mg/L (range 1.11-9.60mg/L) in blood and 3.93mg/g (range 0.91-7.25mg/g) in urine; in the third group it was: 11.8mg/L (range 3.95-24.12mg/L) in blood and 9.83mg/g (range 3.67-21.90mg/g) in urine. The results obtained in blood and urine samples showed a statistically significant difference among groups (pblood and urine samples a mean difference at 20°C compared to -20°C not statistically significant at the 10% level. These findings allow us to affirm that the PMI strongly affects the post mortem production of GHB in blood and urine samples. Regarding the new formation of GHB in vitro both in blood and urine samples of the three groups, which have been stored at -20°C, 4°C and 20°C over a period of one month, although there was no significant increases of

  4. Post-Mortem Analysis after High-Power Operation of the TD24_R05 Tested in Xbox_1

    CERN Document Server

    Degiovanni, Alberto; Mouriz Irazabal, Nerea; Aicheler, Markus

    2016-01-01

    The CLIC prototype structure TD24_R05 has been high power tested in Xbox_1 in 2013. This report summarizes all examinations conducted after the high power test including bead-pull measurements, structure cutting, metrology and SEM observations. A synthesis of the various results is then made. The structure developed a hot cell progressively during operation and detuning was observed after the test was complete. The post mortem examination clearly showed a developed standing wave pattern which was explained by the physical deformation of one of the coupler iris. An elevated breakdown count through SEM imaging in the suspected hot cell however could not be confirmed. Neither any particular feature offering an explanation for the observed longitudinal breakdown distribution could be detected.

  5. Development of fetal brain of 20 weeks gestational age: Assessment with post-mortem Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Zhang Zhonghe; Liu Shuwei; Lin Xiangtao; Teng Gaojun; Yu Taifei; Fang Fang; Zang Fengchao

    2011-01-01

    Background: The 20th week gestational age (GA) is at mid-gestation and corresponds to the age at which the termination of pregnancy in several countries and the first Magnetic Resonance Imaging (MRI) can be performed, and at which the premature babies may survive. However, at present, very little is known about the exact anatomical character at this GA. Objective: To delineate the developing fetal brain of 20 weeks GA and obtain the three dimensional visualization model. Materials and methods: 20 fetal specimens were scanned by 3.0 T and 7.0 T post-mortem MRI, and the three dimensional visualization model was obtained with Amira 4.1. Results: Most of the sulci or their anlage, except the postcentral sulcus and intraparietal sulcus, were present. The laminar organization, described as layers with different signal intensities, was most clearly distinguished at the parieto-occipital lobe and peripheral regions of the hippocampus. The basal nuclei could be clearly visualized, and the brain stem and cerebellum had formed their common shape. On the visualization model, the shape and relative relationship of the structures could be appropriately delineated. The ranges of normal values of the brain structures were obtained, but no sexual dimorphisms or cerebral asymmetries were found. Conclusions: The developing fetal brain of 20 weeks GA can be clearly delineated on 3.0 T and 7.0 T post-mortem MRIs, and the three dimensional visualization model supplies great help in precise cognition of the immature brain. These results may have positive influences on the evaluation of the fetal brain in the uterus.

  6. Minimally invasive autopsy employing post-mortem CT and targeted coronary angiography: evaluation of its application to a routine Coronial service.

    Science.gov (United States)

    Roberts, Ian S D; Traill, Zoe C

    2014-01-01

    Post-mortem imaging is a potential alternative to traditional medicolegal autopsy. We investigate the reduction in number of invasive autopsies required by use of post-mortem CT ± coronary angiography. A total of 120 adult deaths referred to the Coroner were investigated by CT, with coronary angiography employed only for the second series of 60 cases, in order to determine the added value of angiography. The confidence of imaging cause of death was classified as definite (no autopsy), probable, possible or unascertained. Invasive autopsy was not required in 38% of cases without coronary angiography and 70% of cases with angiography. Full autopsy, including brain dissection, was required in only 9% of cases. There was complete agreement between autopsy and radiological causes of death in the cases with a 'probable' imaging cause of death, indicating that cases for which imaging provides an accurate cause of death without autopsy were identified correctly. In two patients, CT demonstrated unsuspected fractures, not detected at subsequent autopsy. A two-thirds reduction in the number of invasive coronial autopsies can be achieved by use of post-mortem CT plus coronary angiography. At the same time, use of post-mortem CT may improve accuracy of diagnosis, particularly for traumatic deaths. © 2013 John Wiley & Sons Ltd.

  7. Clinical Pharmacology and Pharmacokinetics of Levetiracetam

    Directory of Open Access Journals (Sweden)

    Chanin Clark Wright

    2013-12-01

    Full Text Available Status epilepticus and acute repetitive seizures still pose a management challenge despite the recent advances in the field of epilepsy. Parenteral formulations of old anticonvulsants are still a cornerstone in acute seizure management and are approved by the FDA. Intravenous levetiracetam, a second generation anticonvulsant, is approved by the FDA as an adjunctive treatment in patients 16 years or older when oral administration is not available. Data have shown that it has a unique mechanism of action, linear pharmacokinetics and no known drug interactions with other anticonvulsants. In this paper, we will review the current literature about the pharmacology and pharmacokinetics of intravenous levetiracetam and the safety profile of this new anticonvulsant in acute seizure management of both adults and children.

  8. Assessing various Infrared (IR) microscopic imaging techniques for post-mortem interval evaluation of human skeletal remains

    Science.gov (United States)

    Roider, Clemens; Ritsch-Marte, Monika; Pemberger, Nadin; Cemper-Kiesslich, Jan; Hatzer-Grubwieser, Petra; Parson, Walther; Pallua, Johannes Dominikus

    2017-01-01

    Due to the influence of many environmental processes, a precise determination of the post-mortem interval (PMI) of skeletal remains is known to be very complicated. Although methods for the investigation of the PMI exist, there still remains much room for improvement. In this study the applicability of infrared (IR) microscopic imaging techniques such as reflection-, ATR- and Raman- microscopic imaging for the estimation of the PMI of human skeletal remains was tested. PMI specific features were identified and visualized by overlaying IR imaging data with morphological tissue structures obtained using light microscopy to differentiate between forensic and archaeological bone samples. ATR and reflection spectra revealed that a more prominent peak at 1042 cm-1 (an indicator for bone mineralization) was observable in archeological bone material when compared with forensic samples. Moreover, in the case of the archaeological bone material, a reduction in the levels of phospholipids, proteins, nucleic acid sugars, complex carbohydrates as well as amorphous or fully hydrated sugars was detectable at (reciprocal wavelengths/energies) between 3000 cm-1 to 2800 cm-1. Raman spectra illustrated a similar picture with less ν2PO43−at 450 cm-1 and ν4PO43− from 590 cm-1 to 584 cm-1, amide III at 1272 cm-1 and protein CH2 deformation at 1446 cm-1 in archeological bone material/samples/sources. A semi-quantitative determination of various distributions of biomolecules by chemi-maps of reflection- and ATR- methods revealed that there were less carbohydrates and complex carbohydrates as well as amorphous or fully hydrated sugars in archaeological samples compared with forensic bone samples. Raman- microscopic imaging data showed a reduction in B-type carbonate and protein α-helices after a PMI of 3 years. The calculated mineral content ratio and the organic to mineral ratio displayed that the mineral content ratio increases, while the organic to mineral ratio decreases with

  9. Post-mortem computed tomography findings of the lungs: Retrospective review and comparison with autopsy results of 30 infant cases

    Energy Technology Data Exchange (ETDEWEB)

    Kawasumi, Yusuke, E-mail: ssu@rad.med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Clinical Imaging, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Usui, Akihito, E-mail: t7402r0506@med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Diagnostic Image Analysis, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Hosokai, Yoshiyuki, E-mail: hosokai@med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Diagnostic Image Analysis, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Igari, Yui, E-mail: igari@forensic.med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Forensic Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Hosoya, Tadashi [Tohoku University Graduate School of Medicine, Department of Forensic Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Hayashizaki, Yoshie, E-mail: yoshie@forensic.med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Forensic Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Saito, Haruo, E-mail: hsaito@med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Diagnostic Image Analysis, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Ishibashi, Tadashi, E-mail: tisibasi@med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Clinical Imaging, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan); Funayama, Masato, E-mail: funayama@forensic.med.tohoku.ac.jp [Tohoku University Graduate School of Medicine, Department of Forensic Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 (Japan)

    2015-04-15

    Highlights: •Infant cases frequently show a diffuse increase in the concentration of lung fields on post-mortem computed tomography (PMCT). •In this study, twenty-two of the thirty sudden infant death cases showed increasing concentration in the entire lung field. •Based on the autopsy results, the lungs simply collapsed and no other abnormal lung findings were identified. •The radiologist should not consider increasing concentration in all lung fields as simply a pulmonary disorder when diagnosing the cause of infant death using PMCT. -- Abstract: Objectives: Infant cases frequently show a diffuse increase in the concentration of lung fields on post-mortem computed tomography (PMCT). However, the lungs often show simply atelectasis at autopsy in the absence of any other abnormal changes. Thus, we retrospectively reviewed the PMCT findings of lungs following sudden infant death and correlated them with the autopsy results. Materials and methods: We retrospectively reviewed infant cases (0 year) who had undergone PMCT and a forensic autopsy at our institution between May 2009 and June 2013. Lung opacities were classified according to their type; consolidation, ground-glass opacity and mixed, as well as distribution; bilateral diffuse and areas of sparing. Statistical analysis was performed to assess the relationships among lung opacities, causes of death and resuscitation attempt. Results: Thirty infant cases were selected, which included 22 sudden and unexplained deaths and 8 other causes of death. Resuscitation was attempted in 22 of 30 cases. Bilateral diffuse opacities were observed in 21 of the 30 cases. Of the 21 cases, 18 were sudden and unexplained deaths. Areas of sparing were observed in 4 sudden and unexplained deaths and 5 other causes of death. Distribution of opacities was not significantly associated with causes of death or resuscitation attempt. The 21 cases with bilateral diffuse opacities included 6 consolidations (4 sudden and unexplained

  10. Assessing various Infrared (IR microscopic imaging techniques for post-mortem interval evaluation of human skeletal remains.

    Directory of Open Access Journals (Sweden)

    Claudia Woess

    Full Text Available Due to the influence of many environmental processes, a precise determination of the post-mortem interval (PMI of skeletal remains is known to be very complicated. Although methods for the investigation of the PMI exist, there still remains much room for improvement. In this study the applicability of infrared (IR microscopic imaging techniques such as reflection-, ATR- and Raman- microscopic imaging for the estimation of the PMI of human skeletal remains was tested. PMI specific features were identified and visualized by overlaying IR imaging data with morphological tissue structures obtained using light microscopy to differentiate between forensic and archaeological bone samples. ATR and reflection spectra revealed that a more prominent peak at 1042 cm-1 (an indicator for bone mineralization was observable in archeological bone material when compared with forensic samples. Moreover, in the case of the archaeological bone material, a reduction in the levels of phospholipids, proteins, nucleic acid sugars, complex carbohydrates as well as amorphous or fully hydrated sugars was detectable at (reciprocal wavelengths/energies between 3000 cm-1 to 2800 cm-1. Raman spectra illustrated a similar picture with less ν2PO43-at 450 cm-1 and ν4PO43- from 590 cm-1 to 584 cm-1, amide III at 1272 cm-1 and protein CH2 deformation at 1446 cm-1 in archeological bone material/samples/sources. A semi-quantitative determination of various distributions of biomolecules by chemi-maps of reflection- and ATR- methods revealed that there were less carbohydrates and complex carbohydrates as well as amorphous or fully hydrated sugars in archaeological samples compared with forensic bone samples. Raman- microscopic imaging data showed a reduction in B-type carbonate and protein α-helices after a PMI of 3 years. The calculated mineral content ratio and the organic to mineral ratio displayed that the mineral content ratio increases, while the organic to mineral ratio

  11. Assessing various Infrared (IR) microscopic imaging techniques for post-mortem interval evaluation of human skeletal remains.

    Science.gov (United States)

    Woess, Claudia; Unterberger, Seraphin Hubert; Roider, Clemens; Ritsch-Marte, Monika; Pemberger, Nadin; Cemper-Kiesslich, Jan; Hatzer-Grubwieser, Petra; Parson, Walther; Pallua, Johannes Dominikus

    2017-01-01

    Due to the influence of many environmental processes, a precise determination of the post-mortem interval (PMI) of skeletal remains is known to be very complicated. Although methods for the investigation of the PMI exist, there still remains much room for improvement. In this study the applicability of infrared (IR) microscopic imaging techniques such as reflection-, ATR- and Raman- microscopic imaging for the estimation of the PMI of human skeletal remains was tested. PMI specific features were identified and visualized by overlaying IR imaging data with morphological tissue structures obtained using light microscopy to differentiate between forensic and archaeological bone samples. ATR and reflection spectra revealed that a more prominent peak at 1042 cm-1 (an indicator for bone mineralization) was observable in archeological bone material when compared with forensic samples. Moreover, in the case of the archaeological bone material, a reduction in the levels of phospholipids, proteins, nucleic acid sugars, complex carbohydrates as well as amorphous or fully hydrated sugars was detectable at (reciprocal wavelengths/energies) between 3000 cm-1 to 2800 cm-1. Raman spectra illustrated a similar picture with less ν2PO43-at 450 cm-1 and ν4PO43- from 590 cm-1 to 584 cm-1, amide III at 1272 cm-1 and protein CH2 deformation at 1446 cm-1 in archeological bone material/samples/sources. A semi-quantitative determination of various distributions of biomolecules by chemi-maps of reflection- and ATR- methods revealed that there were less carbohydrates and complex carbohydrates as well as amorphous or fully hydrated sugars in archaeological samples compared with forensic bone samples. Raman- microscopic imaging data showed a reduction in B-type carbonate and protein α-helices after a PMI of 3 years. The calculated mineral content ratio and the organic to mineral ratio displayed that the mineral content ratio increases, while the organic to mineral ratio decreases with time

  12. Using bacterial and necrophagous insect dynamics for post-mortem interval estimation during cold season: Novel case study in Romania.

    Science.gov (United States)

    Iancu, Lavinia; Carter, David O; Junkins, Emily N; Purcarea, Cristina

    2015-09-01

    Considering the biogeographical characteristics of forensic entomology, and the recent development of forensic microbiology as a complementary approach for post-mortem interval estimation, the current study focused on characterizing the succession of necrophagous insect species and bacterial communities inhabiting the rectum and mouth cavities of swine (Sus scrofa domesticus) carcasses during a cold season outdoor experiment in an urban natural environment of Bucharest, Romania. We monitored the decomposition process of three swine carcasses during a 7 month period (November 2012-May 2013) corresponding to winter and spring periods of a temperate climate region. The carcasses, protected by wire cages, were placed on the ground in a park type environment, while the meteorological parameters were constantly recorded. The succession of necrophagous Diptera and Coleoptera taxa was monitored weekly, both the adult and larval stages, and the species were identified both by morphological and genetic characterization. The structure of bacterial communities from swine rectum and mouth tissues was characterized during the same time intervals by denaturing gradient gel electrophoresis (DGGE) and sequencing of 16S rRNA gene fragments. We observed a shift in the structure of both insect and bacterial communities, primarily due to seasonal effects and the depletion of the carcass. A total of 14 Diptera and 6 Coleoptera species were recorded on the swine carcasses, from which Calliphora vomitoria and C. vicina (Diptera: Calliphoridae), Necrobia violacea (Coleoptera: Cleridae) and Thanatophilus rugosus (Coleoptera: Silphidae) were observed as predominant species. The first colonizing wave, primarily Calliphoridae, was observed after 15 weeks when the temperature increased to 13°C. This was followed by Muscidae, Fanniidae, Anthomyiidae, Sepsidae and Piophilidae. Families belonging to Coleoptera Order were observed at week 18 when temperatures raised above 18°C, starting with

  13. Post-mortem computed tomography findings of the lungs: Retrospective review and comparison with autopsy results of 30 infant cases

    International Nuclear Information System (INIS)

    Kawasumi, Yusuke; Usui, Akihito; Hosokai, Yoshiyuki; Igari, Yui; Hosoya, Tadashi; Hayashizaki, Yoshie; Saito, Haruo; Ishibashi, Tadashi; Funayama, Masato

    2015-01-01

    Highlights: •Infant cases frequently show a diffuse increase in the concentration of lung fields on post-mortem computed tomography (PMCT). •In this study, twenty-two of the thirty sudden infant death cases showed increasing concentration in the entire lung field. •Based on the autopsy results, the lungs simply collapsed and no other abnormal lung findings were identified. •The radiologist should not consider increasing concentration in all lung fields as simply a pulmonary disorder when diagnosing the cause of infant death using PMCT. -- Abstract: Objectives: Infant cases frequently show a diffuse increase in the concentration of lung fields on post-mortem computed tomography (PMCT). However, the lungs often show simply atelectasis at autopsy in the absence of any other abnormal changes. Thus, we retrospectively reviewed the PMCT findings of lungs following sudden infant death and correlated them with the autopsy results. Materials and methods: We retrospectively reviewed infant cases (0 year) who had undergone PMCT and a forensic autopsy at our institution between May 2009 and June 2013. Lung opacities were classified according to their type; consolidation, ground-glass opacity and mixed, as well as distribution; bilateral diffuse and areas of sparing. Statistical analysis was performed to assess the relationships among lung opacities, causes of death and resuscitation attempt. Results: Thirty infant cases were selected, which included 22 sudden and unexplained deaths and 8 other causes of death. Resuscitation was attempted in 22 of 30 cases. Bilateral diffuse opacities were observed in 21 of the 30 cases. Of the 21 cases, 18 were sudden and unexplained deaths. Areas of sparing were observed in 4 sudden and unexplained deaths and 5 other causes of death. Distribution of opacities was not significantly associated with causes of death or resuscitation attempt. The 21 cases with bilateral diffuse opacities included 6 consolidations (4 sudden and unexplained

  14. DNA quality and quantity from up to 16 years old post-mortem blood stored on FTA cards.

    Science.gov (United States)

    Rahikainen, Anna-Liina; Palo, Jukka U; de Leeuw, Wiljo; Budowle, Bruce; Sajantila, Antti

    2016-04-01

    Blood samples preserved on FTA cards offer unique opportunities for genetic research. DNA recovered from these cards should be stable for long periods of time. However, it is not well established as how well the DNA stored on FTA card for substantial time periods meets the demands of forensic or genomic DNA analyses and especially so for from post-mortem (PM) samples in which the quality can vary upon initial collection. The aim of this study was to evaluate the time-dependent degradation on DNA quality and quantity extracted from up to 16 years old post-mortem bloodstained FTA cards. Four random FTA samples from eight time points spanning 1998 to 2013 (n=32) were collected and extracted in triplicate. The quantity and quality of the extracted DNA samples were determined with Quantifiler(®) Human Plus (HP) Quantification kit. Internal sample and sample-to-sample variation were evaluated by comparing recovered DNA yields. The DNA from the triplicate samplings were subsequently combined and normalized for further analysis. The practical effect of degradation on DNA quality was evaluated from normalized samples both with forensic and pharmacogenetic target markers. Our results suggest that (1) a PM change, e.g. blood clotting prior to sampling, affects the recovered DNA yield, creating both internal and sample-to-sample variation; (2) a negative correlation between the FTA card storage time and DNA quantity (r=-0.836 at the 0.01 level) was observed; (3) a positive correlation (r=0.738 at the level 0.01) was found between FTA card storage time and degradation levels. However, no inhibition was observed with the method used. The effect of degradation was manifested clearly with functional applications. Although complete STR-profiles were obtained for all samples, there was evidence of degradation manifested as decreased peak heights in the larger-sized amplicons. Lower amplification success was notable with the large 5.1 kb CYP2D6 gene fragment which strongly supports

  15. Cerebellar oxidative DNA damage and altered DNA methylation in the BTBR T+tf/J mouse model of autism and similarities with human post mortem cerebellum.

    Directory of Open Access Journals (Sweden)

    Svitlana Shpyleva

    Full Text Available The molecular pathogenesis of autism is complex and involves numerous genomic, epigenomic, proteomic, metabolic, and physiological alterations. Elucidating and understanding the molecular processes underlying the pathogenesis of autism is critical for effective clinical management and prevention of this disorder. The goal of this study is to investigate key molecular alterations postulated to play a role in autism and their role in the pathophysiology of autism. In this study we demonstrate that DNA isolated from the cerebellum of BTBR T+tf/J mice, a relevant mouse model of autism, and from human post-mortem cerebellum of individuals with autism, are both characterized by an increased levels of 8-oxo-7-hydrodeoxyguanosine (8-oxodG, 5-methylcytosine (5mC, and 5-hydroxymethylcytosine (5hmC. The increase in 8-oxodG and 5mC content was associated with a markedly reduced expression of the 8-oxoguanine DNA-glycosylase 1 (Ogg1 and increased expression of de novo DNA methyltransferases 3a and 3b (Dnmt3a and Dnmt3b. Interestingly, a rise in the level of 5hmC occurred without changes in the expression of ten-eleven translocation expression 1 (Tet1 and Tet2 genes, but significantly correlated with the presence of 8-oxodG in DNA. This finding and similar elevation in 8-oxodG in cerebellum of individuals with autism and in the BTBR T+tf/J mouse model warrant future large-scale studies to specifically address the role of OGG1 alterations in pathogenesis of autism.

  16. ORIGINAL ARTICLES Pharmacologically active: clinical trials and ...

    African Journals Online (AJOL)

    2008-01-22

    Jan 22, 2008 ... The US database, on the other hand, clearly identifies 172 ... operating within extended clinical trials R&D value chains. Companies often ... Source: CeSTII Survey Management and Results System internal database. Table III.

  17. Clinical Pharmacology of Chemotherapy Agents in Older People with Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoye He

    2011-01-01

    Full Text Available Populations around the world are aging, and the associated increase in cancer incidence has led to the recognition of the importance of geriatric oncology. Chronological age is a poor determinant of pharmacological response to cancer chemotherapy agents. Age-associated changes in physiology and organ function have a significant impact on the clinical pharmacology of cancer chemotherapy agents used in cancer treatment. Altered response to medicines in older people is a consequence of changes in body composition, organ function, concomitant pathophysiology, multiple medications, genetic determinants of drug response, and patient's clinical status. These issues highlight the need to individualize the management of cancer in the older people with consideration of age-related changes in the clinical pharmacology of cancer drugs, analgesics, and adjunctive therapies.

  18. The internet as a tool in clinical pharmacology

    Science.gov (United States)

    Castel, Josep-Maria; Figueras, Albert; Vigo, Joan-Miquel

    2006-01-01

    The invention of the internet and the world-wide web was a landmark that has affected many aspects of everyday life, but is so recent and dynamic that many of its potential uses are still being explored. Aside from its purely commercial use as a virtual pharmacy (e-commerce), the internet is useful in at least three aspects related to clinical pharmacology: communication, training and research. In this paper we briefly review several internet applications related to clinical pharmacology and describe, as an example, the logistics of a multicentre research collaboration related to the promotion of rational drug use in the prevention of postpartum haemorrhage. PMID:16722847

  19. A Clinical Pharmacology Course for Veterinary Students.

    Science.gov (United States)

    Paulsen, Lynn Mulcahy

    1983-01-01

    A one-semester, two-credit course is described that was developed cooperatively by the colleges of pharmacy and veterinary medicine at Washington State University to help resolve an acute shortage of clinical pharmacologists in veterinary medicine and veterinary medical education. Course procedures, content, and evaluation are outlined (MSE)

  20. ORIGINAL ARTICLES Pharmacologically active: clinical trials and ...

    African Journals Online (AJOL)

    2008-01-22

    Jan 22, 2008 ... companies to manufacture pharmaceuticals, 24 to carry out quality control and ... represents a 3% real growth from 2004/2005, it represents a slight decline from ... manufacturer for the pharmas, or can it leverage strengths in medical ... increased clinical trials activity, R&D investment is too low to make it a ...

  1. Post-mortem whole body computed tomography of opioid (heroin and methadone) fatalities: frequent findings and comparison to autopsy

    Energy Technology Data Exchange (ETDEWEB)

    Winklhofer, Sebastian; Stolzmann, Paul [University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Surer, Eddie; Ampanozi, Garyfalia; Thali, Michael; Schweitzer, Wolf [University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); Ruder, Thomas [University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); University Hospital Bern, Institute of Diagnostic, Interventional and Pediatric Radiology, Bern (Switzerland); Elliott, Marina [Simon Fraser University, Department of Archaeology, Burnaby, BC (Canada); Oestreich, Andrea; Kraemer, Thomas [University of Zurich, Department of Forensic Pharmacology and Toxicology, Institute of Forensic Medicine, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2014-06-15

    To investigate frequent findings in cases of fatal opioid intoxication in whole-body post-mortem computed tomography (PMCT). PMCT of 55 cases in which heroin and/or methadone had been found responsible for death were retrospectively evaluated (study group), and were compared with PMCT images of an age- and sex-matched control group. Imaging results were compared with conventional autopsy. The most common findings in the study group were: pulmonary oedema (95 %), aspiration (66 %), distended urinary bladder (42 %), cerebral oedema (49 %), pulmonary emphysema (38 %) and fatty liver disease (36 %). These PMCT findings occurred significantly more often in the study group than in the control group (p < 0.05). The combination of lung oedema, brain oedema and distended urinary bladder was seen in 26 % of the cases in the study group but never in the control group (0 %). This triad, as indicator of opioid-related deaths, had a specificity of 100 %, as confirmed by autopsy and toxicological analysis. Frequent findings in cases of fatal opioid intoxication were demonstrated. The triad of brain oedema, lung oedema and a distended urinary bladder on PMCT was highly specific for drug-associated cases of death. (orig.)

  2. The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression

    Directory of Open Access Journals (Sweden)

    Craig Ian W

    2006-02-01

    Full Text Available Abstract Background The COMT gene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression of COMT is altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val158Met polymorphism. Method In this study we examined the expression levels of COMT mRNA using quantitative RT-PCR in 60 post mortem cerebellum samples derived from individuals with schizophrenia, bipolar disorder, depression, and no history of psychopathology. Furthermore, we have examined the methylation status of two CpG sites in the promoter region of the gene. Results We found no evidence of altered COMT expression or methylation in any of the psychiatric diagnoses examined. We did, however, find evidence to suggest that genotype is related to COMT gene expression, replicating the findings of two previous studies. Specifically, val158met (rs165688; Val allele rs737865 (G allele and rs165599 (G allele all showed reduced expression (P COMT expression, with females exhibiting significantly greater levels of COMT mRNA. Conclusion The expression of COMT does not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gene.

  3. Properties of raw meat and meat curry from spent goat in relation with post-mortem handling conditions.

    Science.gov (United States)

    Narayan, Raj; Mendiratta, S K; Mane, B G

    2013-04-01

    The properties of raw meat and meat curry from spent goat meat in relation with post-mortem handling conditions were evaluated. The conditions evaluated were: cooking of meat within 1-2 h post-slaughter (condition 1); deboning meat storage at 25 ± 2 °C for 5-6 h and cooking (condition 2); post-slaughter storage of carcass at room temperature for 5-6 h, then deboning followed by storage of meat at refrigeration temperature for 5-6 h and cooking (condition 3); deboning and storage of meat at 25 ± 2 °C for 10-12 h and cooking (condition 4). Significant difference was observed in pH values in condition 1 (p meat as compared to the conditions 2, 3 and 4. However, the moisture content of cooked meat was significantly higher (p meat chunks, that is, the mean value was significantly higher (p < 0.01) for condition 2 and significantly lower for condition 1. Sensory scores were significantly higher in condition 1 and significantly lower in condition 2. However, sensory scores for condition 4 were almost similar to the condition 1.

  4. Distribution of 5HT2A receptors in the human brain: Comparison of data in vivo and post mortem

    International Nuclear Information System (INIS)

    Forutan, F.; Estalji, S.; Beu, M.; Nikolaus, S.; Vosberg, H.; Mueller-Gaertner, H.W.; Larisch, R.; Hamacher, K.; Coenen, H.H.

    2002-01-01

    Aim: The study presented here firstly compars the distribution of the binding potential of the serotonin-5HT 2A receptor as measured in vivo with data of receptor density taken from literature. Secondly, the sensitivity of the method to detect gradual differences in receptor densities is evaluated. Methods: Positron emission tomography (PET) studies were carried out in 6 healthy volunteers using the selective serotonin-5HT 2A ligand 18 F-altanserin. The binding potential was quantified in 12 regions using Logan's graphical method and the equilibrium method. These data were compared to the distribution of receptor density as taken from literature. Results: The binding data in vivo correlated to autoradiography data (post mortem) with r = 0.83 (Pearson regression coefficient; p 18 F-altanserin and PET in healthy volunteers and the true autoradiographically determined distribution of 5HT 2A receptors in human brains. The in vivo method seems to be sensitive enough to detect changes in receptor density of more than 18%. (orig.)

  5. Influence of carcass weight on meat quality of commercial feedlot steers with similar feedlot, slaughter and post-mortem management.

    Science.gov (United States)

    Agbeniga, Babatunde; Webb, Edward C

    2018-03-01

    The effects of beef carcass weight on muscle pH/temperature profile and selected meat quality attributes were evaluated. Twenty-six carcasses from light (≤260kg, n=15) and heavy (≥290kg, n=11) feedlot steers were randomly allocated and stimulated with low voltage electrical stimulation (LVES) for 30s at 7min post-mortem (pm). Quality evaluations were carried out on samples from the Longissimus et lumborum (LL) muscle from the left side of each carcass. Heavier carcasses showed faster pH decline and slower (P35°C) but there was no sign of sarcomere shortening in any carcass. Significantly lower (P0.05) drip loss at 3 and 14days pm as well as higher L* (meat lightness) (P<0.05) and C* (chroma) (P<0.05) values early (2days) pm. However, at 14days pm, there were no significant differences between the light and heavy carcasses in terms of L* and C*. No significant difference was observed between heavy and light carcasses in terms of H* at 2 and 14days pm. The study showed that heavier carcasses which favor slaughter house pricing can be produced and processed alongside lighter carcasses without significant detrimental effects on meat quality by using low voltage electrical stimulation (LVES). Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Distinction between saltwater drowning and freshwater drowning by assessment of sinus fluid on post-mortem computed tomography

    International Nuclear Information System (INIS)

    Kawasumi, Yusuke; Sato, Yuki; Sato, Yumi; Ishibashi, Tadashi; Usui, Akihito; Daigaku, Nami; Hosokai, Yoshiyuki; Hayashizaki, Yoshie; Funayama, Masato

    2016-01-01

    To evaluate the difference in sinus fluid volume and density between saltwater and freshwater drowning and diagnose saltwater drowning in distinction from freshwater drowning. Ninety-three drowning cases (22 saltwater and 71 freshwater) were retrospectively investigated; all had undergone post-mortem CT and forensic autopsy. Sinus fluid volume and density were calculated using a 3D-DICOM workstation, and differences were evaluated. Diagnostic performance of these indicators for saltwater drowning was evaluated using a cut-off value calculated by receiver operating characteristic (ROC) analysis. The median sinus fluid volume was 5.68 mL in cases of saltwater drowning (range 0.08 to 37.55) and 5.46 mL in cases of freshwater drowning (0.02 to 27.68), and the average densities were 47.28 (14.26 to 75.98) HU and 32.56 (-14.38 to 77.43) HU, respectively. While sinus volume did not differ significantly (p = 0.6000), sinus density was significantly higher in saltwater than freshwater drowning cases (p = 0.0002). ROC analysis for diagnosis of saltwater drowning determined the cut-off value as 37.77 HU, with a sensitivity of 77 %, specificity of 72 %, PPV of 46 % and NPV of 91 %. The average density of sinus fluid in cases of saltwater drowning was significantly higher than in freshwater drowning cases; there was no significant difference in the sinus fluid volume. (orig.)

  7. Post-mortem whole body computed tomography of opioid (heroin and methadone) fatalities: frequent findings and comparison to autopsy

    International Nuclear Information System (INIS)

    Winklhofer, Sebastian; Stolzmann, Paul; Surer, Eddie; Ampanozi, Garyfalia; Thali, Michael; Schweitzer, Wolf; Ruder, Thomas; Elliott, Marina; Oestreich, Andrea; Kraemer, Thomas; Alkadhi, Hatem

    2014-01-01

    To investigate frequent findings in cases of fatal opioid intoxication in whole-body post-mortem computed tomography (PMCT). PMCT of 55 cases in which heroin and/or methadone had been found responsible for death were retrospectively evaluated (study group), and were compared with PMCT images of an age- and sex-matched control group. Imaging results were compared with conventional autopsy. The most common findings in the study group were: pulmonary oedema (95 %), aspiration (66 %), distended urinary bladder (42 %), cerebral oedema (49 %), pulmonary emphysema (38 %) and fatty liver disease (36 %). These PMCT findings occurred significantly more often in the study group than in the control group (p < 0.05). The combination of lung oedema, brain oedema and distended urinary bladder was seen in 26 % of the cases in the study group but never in the control group (0 %). This triad, as indicator of opioid-related deaths, had a specificity of 100 %, as confirmed by autopsy and toxicological analysis. Frequent findings in cases of fatal opioid intoxication were demonstrated. The triad of brain oedema, lung oedema and a distended urinary bladder on PMCT was highly specific for drug-associated cases of death. (orig.)

  8. The benefits and pitfalls of post-mortem computed tomography in forensic external examination: A retrospective study of 145 cases.

    Science.gov (United States)

    Willaume, Thibault; Farrugia, Audrey; Kieffer, Estelle-Marie; Charton, Jeanne; Geraut, Annie; Berthelon, Laurent; Bierry, Guillaume; Raul, Jean-Sébastien

    2018-05-01

    Nowadays, post-mortem computed tomography (PMCT) has become an integral part of Forensic practice. The purpose of the study was to determine PMCT impact on diagnosis of the cause of death within the context of the external examination of the body, when autopsy has, at first, not been requested. We reviewed the records of 145 cases for which unenhanced PMCT was performed in addition to the external examination of the body from January 2014 to July 2015 at the Institute of Forensic medicine in Strasbourg (France). We confronted final reports from forensic pathologist to the corresponding PMCT reports. Data were collected in a contingency table and the impact of PMCT on the final conclusions of the forensic pathologist was evaluated via a Chi 2 test. PMCT results significantly impact the final conclusions of forensic pathologist (pforensic pathologist. In other cases (traumatic death), PMCT enables fast and exhaustive lesion assessment. Lastly, there are situations where PMCT may be ineffective (intoxication, hanging or some natural deaths). Performing PMCT within the context of the external examination of the body when autopsy has, at first, not been requested could bring significant benefits in diagnosing the cause of death. The impact of PMCT varies depending on the circumstances of death. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Distinction between saltwater drowning and freshwater drowning by assessment of sinus fluid on post-mortem computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kawasumi, Yusuke; Sato, Yuki; Sato, Yumi; Ishibashi, Tadashi [Tohoku University Graduate School of Medicine, Department of Clinical Imaging, Sendai, Miyagi (Japan); Usui, Akihito; Daigaku, Nami; Hosokai, Yoshiyuki [Tohoku University Graduate School of Medicine, Department of Diagnostic Image Analysis, Sendai, Miyagi (Japan); Hayashizaki, Yoshie; Funayama, Masato [Tohoku University Graduate School of Medicine, Department of Forensic Medicine, Sendai, Miyagi (Japan)

    2016-04-15

    To evaluate the difference in sinus fluid volume and density between saltwater and freshwater drowning and diagnose saltwater drowning in distinction from freshwater drowning. Ninety-three drowning cases (22 saltwater and 71 freshwater) were retrospectively investigated; all had undergone post-mortem CT and forensic autopsy. Sinus fluid volume and density were calculated using a 3D-DICOM workstation, and differences were evaluated. Diagnostic performance of these indicators for saltwater drowning was evaluated using a cut-off value calculated by receiver operating characteristic (ROC) analysis. The median sinus fluid volume was 5.68 mL in cases of saltwater drowning (range 0.08 to 37.55) and 5.46 mL in cases of freshwater drowning (0.02 to 27.68), and the average densities were 47.28 (14.26 to 75.98) HU and 32.56 (-14.38 to 77.43) HU, respectively. While sinus volume did not differ significantly (p = 0.6000), sinus density was significantly higher in saltwater than freshwater drowning cases (p = 0.0002). ROC analysis for diagnosis of saltwater drowning determined the cut-off value as 37.77 HU, with a sensitivity of 77 %, specificity of 72 %, PPV of 46 % and NPV of 91 %. The average density of sinus fluid in cases of saltwater drowning was significantly higher than in freshwater drowning cases; there was no significant difference in the sinus fluid volume. (orig.)

  10. [Post mortem temperature equilibration of the structures of the head. I. Thermometric techniques and principal investigations (author's transl)].

    Science.gov (United States)

    Brinkmann, B; May, D; Riemann, U

    1976-06-30

    Special thin and flexible thermometric probes showing a diameter of 1 mm and a sharp end were used for post mortem (p.m.) thermometric studies in several tissues. Brain temperatures were measured by inserting a double probe through the superior orbital fissura thus allowing to record the central and the peripheral brain regions separately. Another probe was inserted into the galea and a fourth into the liver. Temperature changes were recorded simultaneously. Many variables of the human head were measured. Sixteen corpses were investigated. The results were as follows: 1. Of all temperature curves registered those of the central brain regions showed the smallest variance. 2. The p.m. temperature curve of the brain shows a sigmoid shape with a rather short "plateau" in the beginning. 3. In the early p.m. phase there is an increasing difference of temperatures between central and peripheral brain regions amounting to 2-4, 6 degrees C in the time period between 78th and 128th minute. 4. The insertion of the thin probes does not cause visible damages. Thus it should be considered for use in forensic practice. 5. Some artificial "head models" were constructed and temperature decrease recorded after warming. The curves showed the same type of sigmoid shape as those obtained from the corpses. 6. Of the possible variables measured that could influence the temperature decrease only the density of the hair seems to be of interest.

  11. Virtual forensic entomology: improving estimates of minimum post-mortem interval with 3D micro-computed tomography.

    Science.gov (United States)

    Richards, Cameron S; Simonsen, Thomas J; Abel, Richard L; Hall, Martin J R; Schwyn, Daniel A; Wicklein, Martina

    2012-07-10

    We demonstrate how micro-computed tomography (micro-CT) can be a powerful tool for describing internal and external morphological changes in Calliphora vicina (Diptera: Calliphoridae) during metamorphosis. Pupae were sampled during the 1st, 2nd, 3rd and 4th quarter of development after the onset of pupariation at 23 °C, and placed directly into 80% ethanol for preservation. In order to find the optimal contrast, four batches of pupae were treated differently: batch one was stained in 0.5M aqueous iodine for 1 day; two for 7 days; three was tagged with a radiopaque dye; four was left unstained (control). Pupae stained for 7d in iodine resulted in the best contrast micro-CT scans. The scans were of sufficiently high spatial resolution (17.2 μm) to visualise the internal morphology of developing pharate adults at all four ages. A combination of external and internal morphological characters was shown to have the potential to estimate the age of blowfly pupae with a higher degree of accuracy and precision than using external morphological characters alone. Age specific developmental characters are described. The technique could be used as a measure to estimate a minimum post-mortem interval in cases of suspicious death where pupae are the oldest stages of insect evidence collected. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  12. Post-mortem prediction of primal and selected retail cut weights of New Zealand lamb from carcass and animal characteristics.

    Science.gov (United States)

    Ngo, L; Ho, H; Hunter, P; Quinn, K; Thomson, A; Pearson, G

    2016-02-01

    Post-mortem measurements (cold weight, grade and external carcass linear dimensions) as well as live animal data (age, breed, sex) were used to predict ovine primal and retail cut weights for 792 lamb carcases. Significant levels of variance could be explained using these predictors. The predictive power of those measurements on primal and retail cut weights was studied by using the results from principal component analysis and the absolute value of the t-statistics of the linear regression model. High prediction accuracy for primal cut weight was achieved (adjusted R(2) up to 0.95), as well as moderate accuracy for key retail cut weight: tenderloins (adj-R(2)=0.60), loin (adj-R(2)=0.62), French rack (adj-R(2)=0.76) and rump (adj-R(2)=0.75). The carcass cold weight had the best predictive power, with the accuracy increasing by around 10% after including the next three most significant variables. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Deuterium Inventory in Tore Supra (DITS): 2nd post-mortem analysis campaign and fuel retention in the gaps

    International Nuclear Information System (INIS)

    Dittmar, T.; Tsitrone, E.; Pegourie, B.; Cadez, I.; Pelicon, P.; Gauthier, E.; Languille, P.; Likonen, J.; Litnovsky, A.; Markelj, S.; Martin, C.; Mayer, M.; Pascal, J.-Y.; Pardanaud, C.; Philipps, V.; Roth, J.; Roubin, P.; Vavpetic, P.

    2011-01-01

    A dedicated study on fuel retention has been launched in Tore Supra, which includes a D wall-loading campaign and the dismantling of the main limiter (Deuterium Inventory in Tore Supra, DITS project). This paper presents new results from a second post-mortem analysis campaign on 40 tiles with special emphasis on the D retention in the gaps. SIMS analysis reveals that only 1/3 of the thickness of deposits in the plasma shadowed zones are due to the DITS wall-loading campaign. As pre-DITS deposits contain less D than DITS deposits, the contribution of DITS to the D inventory is about 30-50%. The new estimate for the total amount of D retained in the Tore Supra limiter is 1.7 x 10 24 atoms, close to the previous estimate, with the gap surfaces contributing about 33%. NRA measurements show a stepped decrease of D along the gap with strong asymmetries between different gap orientations.

  14. Outdoor post-mortem bite injuries by Tapinoma nigerrimum (Hymenoptera, Formicidae) on a human corpse: Case report.

    Science.gov (United States)

    Bonacci, Teresa; Vercillo, Vannio

    2015-07-01

    Ants are among the insects that colonize exposed human and animal corpses during the early stage of decomposition. In Calabria, Italy (as well as in other countries), Formicidae have been observed preying on immature stages of Diptera and other insects, as well as causing irregular scalloped areas of superficial skin loss on human corpses and animal carcasses. We present a case of injuries on a human corpse caused by ant feeding. The macroscopic appearance is described and the results of a histochemical investigation of the skin lesions caused by worker ants are reported for the first time. The investigation was carried out on the fresh corpse of a 53-year-old man discovered in a rural area of Cosenza province (Calabria, southern Italy). Numerous irregular areas of superficial skin loss caused by the ant Tapinoma nigerrimum (Nylander 1856) (Hymenoptera, Formicidae) were observed on the body surface, inflicted very early in the post-mortem period. Because the classification of lesions is of crucial importance for forensic investigations, the macroscopic appearance and distribution pattern of the lesions on the corpse are illustrated. The histochemical investigation of the damaged skin explains, for the first time, the mechanism of production of the lesions. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  15. Post-mortem hemoparasite detection in free-living Brazilian brown brocket deer (Mazama gouazoubira, Fischer 1814

    Directory of Open Access Journals (Sweden)

    Júlia Angélica Gonçalves da Silveira

    Full Text Available Tick-borne infections can result in serious health problems for wild ruminants, and some of these infectious agents can be considered zoonosis. The aim of the present study was the post-mortem detection of hemoparasites in free-living Mazama gouazoubira from Minas Gerais state, Brazil. The deer samples consisted of free-living M. gouazoubira (n = 9 individuals that died after capture. Necropsy examinations of the carcasses were performed to search for macroscopic alterations. Organ samples were collected for subsequent imprint slides, and nested PCR assays were performed to detect hemoparasite species. Imprint slide assays from four deer showed erythrocytes infected with Piroplasmida small trophozoites, and A. marginale corpuscles were observed in erythrocytes from two animals. A. marginale and trophozoite co-infections occurred in two deer. A nested PCR analysis of the organs showed that six of the nine samples were positive for Theileria sp., five were positive for A. phagocytophilum and three were positive for A. marginale, with co-infection occurring in four deer. The results of the present study demonstrate that post-mortemdiagnostics using imprint slides and molecular assays are an effective method for detecting hemoparasites in organs.

  16. Clinical Pharmacology Studies in Critically Ill Children

    Science.gov (United States)

    Thakkar, Nilay; Salerno, Sara; Hornik, Christoph P.; Gonzalez, Daniel

    2016-01-01

    Developmental and physiological changes in children contribute to variation in drug disposition with age. Additionally, critically ill children suffer from various life-threatening conditions that can lead to pathophysiological alterations that further affect pharmacokinetics (PK). Some factors that can alter PK in this patient population include variability in tissue distribution caused by protein binding changes and fluid shifts, altered drug elimination due to organ dysfunction, and use of medical interventions that can affect drug disposition (e.g., extracorporeal membrane oxygenation and continuous renal replacement therapy). Performing clinical studies in critically ill children is challenging because there is large inter-subject variability in the severity and time course of organ dysfunction; some critical illnesses are rare, which can affect subject enrollment; and critically ill children usually have multiple organ failure, necessitating careful selection of a study design. As a result, drug dosing in critically ill children is often based on extrapolations from adults or non-critically ill children. Dedicated clinical studies in critically ill children are urgently needed to identify optimal dosing of drugs in this population. This review will summarize the effect of critical illness on pediatric PK, the challenges associated with performing studies in this vulnerable subpopulation, and the clinical PK studies performed to date for commonly used drugs. PMID:27585904

  17. The Pharmacologic and Clinical Effects of Illicit Synthetic Cannabinoids.

    Science.gov (United States)

    White, C Michael

    2017-03-01

    This article presents information on illicitly used synthetic cannabinoids. Synthetic cannabinoids are structurally heterogeneous and commonly used drugs of abuse that act as full agonists of the cannabinoid type-1 receptor but have a variety of additional pharmacologic effects. There are numerous cases of patient harm and death in the United States, Europe, and Australia with many psychological, neurological, cardiovascular, pulmonary, and renal adverse events. Although most users prefer using cannabis, there are convenience, legal, and cost reasons driving the utilization of synthetic cannabinoids. Clinicians should be aware of pharmacologic and clinical similarities and differences between synthetic cannabinoid and cannabis use, the limited ability to detect synthetic cannabinoids in the urine or serum, and guidance to treat adverse events. © 2016, The American College of Clinical Pharmacology.

  18. Identification of post-mortem indicators of welfare of finishing pigs on the day of slaughter

    DEFF Research Database (Denmark)

    Brandt, Pia; Rousing, Tine; Herskin, Mette S

    2013-01-01

    potential welfare indicators for future documentation of welfare of finishing pigs at commercial abattoirs. Behavioural and clinical observations were carried out at unloading, in the lairage and in the race to the stunning chamber in the abattoir. During lairage, behavioural recordings were performed...... by direct observation, whereas at unloading and prior to stunning recordings were performed using video surveillance. Behavioural and handling measurements included: reluctance to move, turning back, slipping, falling and driving of the pigs at unloading, postures during lairage and slipping, falling...

  19. Potentially Treatable Disorder Diagnosed Post Mortem by Exome Analysis in a Boy with Respiratory Distress

    Directory of Open Access Journals (Sweden)

    Valentina Imperatore

    2016-02-01

    Full Text Available We highlight the importance of exome sequencing in solving a clinical case of a child who died at 14 months after a series of respiratory crises. He was the half-brother of a girl diagnosed at 7 years with the early-onset seizure variant of Rett syndrome due to CDKL5 mutation. We performed a test for CDKL5 in the boy, which came back negative. Driven by the mother’s compelling need for a diagnosis, we moved forward performing whole exome sequencing analysis. Surprisingly, two missense mutations in compound heterozygosity were identified in the RAPSN gene encoding a receptor-associated protein with a key role in clustering and anchoring nicotinic acetylcholine receptors at synaptic sites. This gene is responsible for a congenital form of myasthenic syndrome, a disease potentially treatable with cholinesterase inhibitors. Therefore, an earlier diagnosis in this boy would have led to a better clinical management and prognosis. Our study supports the key role of exome sequencing in achieving a definite diagnosis in severe perinatal diseases, an essential step especially when a specific therapy is available.

  20. Post-mortem radiography of the lungs: Experiments to compare various methods of examination and descriptions of their usefulness in actual practice

    International Nuclear Information System (INIS)

    Pankow, W.

    1986-01-01

    Described is the post-mortem examination of the isolated lung using radiologic-morphologic and histologic methods. Comparisons are made ragarding practical value of the conservation techniques chosen, which were the method of Markaria and Heitzmann that is based on fixing in alcohol and air drying and the nitrogen freezing method developed by Rau and colleagues. Both methods ensure adequate visualition of the pulmonary ultrastructure by X-rays, even though this observation should be qualified by the fact that pulmonary tissue fixed in alcohol tends to shrink and that intraalveolar edema are thus artificially reduced. Either of the methods under investigation permits angiographic and bronchographic examinations to be carried out without difficulty. In macroscopic evaluations better results are obtained for lungs fixed in alcohol. Freeze-dried samples offer advantages in the histological assessment of the pulmonary ultrastructure. Post-mortem radiography of the lungs is particularly valuable in the analysis of pathological changes in the pulmonary structure. (MBC) [de

  1. Studies on time of death estimation in the early post mortem period -- application of a method based on eyeball temperature measurement to human bodies.

    Science.gov (United States)

    Kaliszan, Michał

    2013-09-01

    This paper presents a verification of the thermodynamic model allowing an estimation of the time of death (TOD) by calculating the post mortem interval (PMI) based on a single eyeball temperature measurement at the death scene. The study was performed on 30 cases with known PMI, ranging from 1h 35min to 5h 15min, using pin probes connected to a high precision electronic thermometer (Dostmann-electronic). The measured eye temperatures ranged from 20.2 to 33.1°C. Rectal temperature was measured at the same time and ranged from 32.8 to 37.4°C. Ambient temperatures which ranged from -1 to 24°C, environmental conditions (still air to light wind) and the amount of hair on the head were also recorded every time. PMI was calculated using a formula based on Newton's law of cooling, previously derived and successfully tested in comprehensive studies on pigs and a few human cases. Thanks to both the significantly faster post mortem decrease of eye temperature and a residual or nonexistent plateau effect in the eye, as well as practically no influence of body mass, TOD in the human death cases could be estimated with good accuracy. The highest TOD estimation error during the post mortem intervals up to around 5h was 1h 16min, 1h 14min and 1h 03min, respectively in three cases among 30, while for the remaining 27 cases it was not more than 47min. The mean error for all 30 cases was ±31min. All that indicates that the proposed method is of quite good precision in the early post mortem period, with an accuracy of ±1h for a 95% confidence interval. On the basis of the presented method, TOD can be also calculated at the death scene with the use of a proposed portable electronic device (TOD-meter). Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Is survival improved by the use of NIV and PEG in amyotrophic lateral sclerosis (ALS)? A post-mortem study of 80 ALS patients

    OpenAIRE

    Burkhardt, Christian; Neuwirth, Christoph; Sommacal, Andreas; Andersen, Peter M.; Weber, Markus

    2017-01-01

    Background: Non-invasive ventilation (NIV) and percutaneous gastrostomy (PEG) are guideline-recommended interventions for symptom management in amyotrophic lateral sclerosis (ALS). Their effect on survival is controversial and the impact on causes of death is unknown. Objective: To investigate the effect of NIV and PEG on survival and causes of death in ALS patients. Methods: Eighty deceased ALS patients underwent a complete post mortem analysis for causes of death between 2003 and 2015. Fort...

  3. Myocardial contrast defect associated with thrombotic coronary occlusion: Pre-autopsy diagnosis of a cardiac death with post-mortem CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Heon; Cha, Jang Gyu [Dept. of Radiology, Soonchunhyang University Hospital, Bucheon (Korea, Republic of); Park, Hye Jin; Lee, Soo Kyoung; Yang, Kyung Moo [Dept. of Forensic Medicine, National Forensic Service, Wonju (Korea, Republic of)

    2015-10-15

    We report the case of a female who died of suspected acute myocardial infarction. Post-mortem CT angiography (PMCTA) was performed with intravascular contrast infusion before the standard autopsy, and it successfully demonstrated the complete thrombotic occlusion of a coronary artery and also a corresponding perfusion defect on myocardium. We herein describe the PMCTA findings of a cardiac death with special emphasis on the potential benefits of this novel CT technique in forensic practice.

  4. Human pharmacology for addiction medicine: From evidence to clinical recommendations.

    Science.gov (United States)

    Quednow, Boris B; Herdener, Marcus

    2016-01-01

    Substance use disorders (SUD) are complex and often chronic diseases with negative health outcomes and social consequences. Pharmacological treatment options for SUD can be separated in medications for (i) intoxication, (ii) withdrawal, and (iii) reduction of use together with relapse prevention. This chapter will focus on approved or clinically established pharmacological strategies suited to manage symptoms of withdrawal, and to reduce substance use or to promote abstinence. Hereby SUD involving alcohol, nicotine, stimulants, and opioids are primarily discussed as these substances are considered most harmful for both the individual and the society. Moreover, the pharmacotherapy of SUD related to the use of cannabis, benzodiazepines, and gamma-hydroxybutyrate is also briefly reviewed. Since most approved pharmacological treatment options show only moderate effect sizes especially in the long term, the development of new treatment strategies including new drugs, new combinations of available compounds, and biomarkers for response prediction is still warranted. © 2016 Elsevier B.V. All rights reserved.

  5. A comparison between rib fracture patterns in peri- and post-mortem compressive injury in a piglet model.

    Science.gov (United States)

    Bradley, Amanda L; Swain, Michael V; Neil Waddell, J; Das, Raj; Athens, Josie; Kieser, Jules A

    2014-05-01

    Forensic biomechanics is increasingly being used to explain how observed injuries occur. We studied infant rib fractures from a biomechanical and morphological perspective using a porcine model. We used 24, 6th ribs of one day old domestic pigs Sus scrofa, divided into three groups, desiccated (representing post-mortem trauma), fresh ribs with intact periosteum (representing peri-mortem trauma) and those stored at -20°C. Two experiments were designed to study their biomechanical behaviour fracture morphology: ribs were axially compressed and subjected to four-point bending in an Instron 3339 fitted with custom jigs. Morphoscopic analysis of resultant fractures consisted of standard optical methods, micro-CT (μCT) and Scanning Electron Microscopy (SEM). During axial compression fresh ribs did not fracture because of energy absorption capabilities of their soft and fluidic components. In flexure tests, dry ribs showed typical elastic-brittle behaviour with long linear load-extension curves, followed by short non-linear elastic (hyperelastic) behaviour and brittle fracture. Fresh ribs showed initial linear-elastic behaviour, followed by strain softening and visco-plastic responses. During the course of loading, dry bone showed minimal observable damage prior to the onset of unstable fracture. Frozen then thawed bone showed similar patterns to fresh bone. Morphologically, fresh ribs showed extensive periosteal damage to the tensile surface with areas of collagen fibre pull-out along the tensile surface. While all dry ribs fractured precipitously, with associated fibre pull-out, the latter feature was absent in thawed ribs. Our study highlights the fact that under controlled loading, fresh piglet ribs (representing perimortem trauma) did not fracture through bone, but was associated with periosteal tearing. These results suggest firstly, that complete lateral rib fracture in infants may in fact not result from pure compression as has been previously assumed; and

  6. Markers of microglia in post-mortem brain samples from patients with Alzheimer's disease: a systematic review.

    Science.gov (United States)

    Hopperton, K E; Mohammad, D; Trépanier, M O; Giuliano, V; Bazinet, R P

    2018-02-01

    Neuroinflammation is proposed as one of the mechanisms by which Alzheimer's disease pathology, including amyloid-β plaques, leads to neuronal death and dysfunction. Increases in the expression of markers of microglia, the main neuroinmmune cell, are widely reported in brains from patients with Alzheimer's disease, but the literature has not yet been systematically reviewed to determine whether this is a consistent pathological feature. A systematic search was conducted in Medline, Embase and PsychINFO for articles published up to 23 February 2017. Papers were included if they quantitatively compared microglia markers in post-mortem brain samples from patients with Alzheimer's disease and aged controls without neurological disease. A total of 113 relevant articles were identified. Consistent increases in markers related to activation, such as major histocompatibility complex II (36/43 studies) and cluster of differentiation 68 (17/21 studies), were identified relative to nonneurological aged controls, whereas other common markers that stain both resting and activated microglia, such as ionized calcium-binding adaptor molecule 1 (10/20 studies) and cluster of differentiation 11b (2/5 studies), were not consistently elevated. Studies of ionized calcium-binding adaptor molecule 1 that used cell counts almost uniformly identified no difference relative to control, indicating that increases in activation occurred without an expansion of the total number of microglia. White matter and cerebellum appeared to be more resistant to these increases than other brain regions. Nine studies were identified that included high pathology controls, patients who remained free of dementia despite Alzheimer's disease pathology. The majority (5/9) of these studies reported higher levels of microglial markers in Alzheimer's disease relative to controls, suggesting that these increases are not solely a consequence of Alzheimer's disease pathology. These results show that increased markers

  7. Layering of stomach contents in drowning cases in post-mortem computed tomography compared to forensic autopsy.

    Science.gov (United States)

    Gotsmy, Walther; Lombardo, Paolo; Jackowski, Christian; Brencicova, Eva; Zech, Wolf-Dieter

    2018-04-24

    In forensic autopsy, the analysis of stomach contents is important when investigating drowning cases. Three-layering of stomach contents may be interpreted as a diagnostic hint to drowning due to swallowing of larger amounts of water or other drowning media. The authors experienced frequent discrepancies of numbers of stomach content layering in drowning cases between post-mortem computed tomography (PMCT) and autopsy in forensic casework. Therefore, the goal of this study was to compare layering of stomach contents in drowning cases between PMCT and forensic autopsy. Drowning cases (n = 55; 40 male, 15 female, mean age 45.3 years; mean amount of stomach content 223 ml) that received PMCT prior to forensic autopsy were retrospectively analyzed by a forensic pathologist and a radiologist. Number of layers of stomach content in PMCT were compared to number of layers at forensic autopsy. In 28 of the 55 evaluated drowning cases, a discrepancy between layering of stomach contents at autopsy compared to PMCT was observed: 1 layer at autopsy (n = 28): 50% discrepancy to PMCT, 2 layers (n = 20): 45% discrepancy, and 3 layers (n = 7): 71.4% discrepancy. Sensitivity of correctly determining layering (as observed at forensic autopsy) in PMCT was 52% (positive predictive value 44.8%). Specificity was 46.6% (negative predictive value 53.8%). In a control group (n = 35) of non-drowning cases, three-layering of stomach contents was not observed. Discrepancies of observed numbers of stomach content layers between PMCT and forensic autopsy are a frequent finding possibly due to stomach content sampling technique at autopsy and movement of the corpse prior to PMCT and autopsy. Three-layering in PMCT, if indeed present, may be interpreted as a hint to drowning.

  8. GABAergic system impairment in the hippocampus and superior temporal gyrus of patients with paranoid schizophrenia: A post-mortem study.

    Science.gov (United States)

    Steiner, Johann; Brisch, Ralf; Schiltz, Kolja; Dobrowolny, Henrik; Mawrin, Christian; Krzyżanowska, Marta; Bernstein, Hans-Gert; Jankowski, Zbigniew; Braun, Katharina; Schmitt, Andrea; Bogerts, Bernhard; Gos, Tomasz

    2016-11-01

    Glutamic acid decarboxylase (GAD) is a key enzyme in GABA synthesis and alterations in GABAergic neurotransmission related to glial abnormalities are thought to play a crucial role in the pathophysiology of schizophrenia. This study aimed to identify potential differences regarding the neuropil expression of GAD between paranoid and residual schizophrenia. GAD65/67 immunostained histological sections were evaluated by quantitative densitometric analysis of GAD-immunoreactive (ir) neuropil. Regions of interest were the hippocampal formation (CA1 field and dentate gyrus [DG]), superior temporal gyrus (STG), and laterodorsal thalamic nucleus (LD). Data from 16 post-mortem schizophrenia patient samples (10 paranoid and 6 residual schizophrenia cases) were compared with those from 16 matched controls. Overall, schizophrenia patients showed a lower GAD-ir neuropil density (P=0.014), particularly in the right CA1 (P=0.033). However, the diagnostic subgroups differed significantly (Pparanoid versus residual patients (P=0.036) and controls (Pparanoid versus residual schizophrenia cases (P=0.042). GAD-ir neuropil density correlated positively with antipsychotic dosage, particularly in CA1 (right: r=0.850, P=0.004; left: r=0.800, P=0.010). Our finding of decreased relative density of GAD-ir neuropil suggests hypofunction of the GABAergic system, particularly in hippocampal CA1 field and STG layer V of patients with paranoid schizophrenia. The finding that antipsychotic medication seems to counterbalance GABAergic hypofunction in schizophrenia patients suggests the possibility of exploring new treatment avenues which target this system. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Quantitative evaluation of volatile hydrocarbons in post-mortem blood in forensic autopsy cases of fire-related deaths.

    Science.gov (United States)

    Yonemitsu, Kosei; Sasao, Ako; Oshima, Toru; Mimasaka, Sohtaro; Ohtsu, Yuki; Nishitani, Yoko

    2012-04-10

    Volatile hydrocarbons in post-mortem blood from victims of fires were analyzed quantitatively by headspace gas chromatography mass spectrometry. The benzene and styrene concentrations in the blood were positively correlated with the carboxyhemoglobin (CO-Hb) concentration, which is evidence that the deceased inhaled the hydrocarbons and carbon monoxide simultaneously. By contrast, the concentrations of toluene and CO-Hb in the blood were not significantly correlated. This lack of correlation could be explained by two different sources of toluene, with low blood concentrations of toluene arising when the deceased inhaled smoke and high blood concentrations of toluene arising when the deceased inhaled petroleum vapor or other unknown vapors. The quantity of soot deposited in the respiratory tract was classified into four grades (-, 1+, 2+, 3+). The mean CO-Hb concentration in the 1+ soot group was significantly lower than those in the 2+ (ptypes of smoke produced by different materials. For example, petroleum combustion with a limited supply of oxygen, like in a compartment fire, may produce a large volume of dense black smoke that contains a large quantity of soot. Soot deposits in the airways and the blood CO-Hb concentration are basic and essential autopsy findings that are used to investigate fire-related deaths. The quantitative GC-MS analysis of blood volatile hydrocarbons can provide additional useful information on the cause of the fire and the circumstances surrounding the death. In combination, these three findings are useful for the reconstruction of cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Phytochemistry, pharmacology, and clinical trials of Morus alba.

    Science.gov (United States)

    Chan, Eric Wei-Chiang; Lye, Phui-Yan; Wong, Siu-Kuin

    2016-01-01

    The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  11. Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in relation to traumatic brain injury and hippocampal sclerosis: a post-mortem study.

    Science.gov (United States)

    Thom, Maria; Liu, Joan Y W; Thompson, Pam; Phadke, Rahul; Narkiewicz, Marta; Martinian, Lillian; Marsdon, Derek; Koepp, Matthias; Caboclo, Luis; Catarino, Claudia B; Sisodiya, Sanjay M

    2011-10-01

    The long-term pathological effects of chronic epilepsy on normal brain ageing are unknown. Previous clinical and epidemiological studies show progressive cognitive decline in subsets of patients and an increased prevalence of Alzheimer's disease in epilepsy. In a post-mortem series of 138 patients with long-term, mainly drug-resistant epilepsy, we carried out Braak staging for Alzheimer's disease neurofibrillary pathology using tau protein immunohistochemistry. The stages were compared with clinicopathological factors, including seizure history and presence of old traumatic brain injury. Overall, 31% of cases were Braak Stage 0, 36% Stage I/II, 31% Stage III/IV and 2% Stage V/VI. The mean age at death was 56.5 years and correlated with Braak stage (P < 0.001). Analysis of Braak stages within age groups showed a significant increase in mid-Braak stages (III/IV), in middle age (40-65 years) compared with data from an ageing non-epilepsy series (P < 0.01). There was no clear relationship between seizure type (generalized or complex partial), seizure frequency, age of onset and duration of epilepsy with Braak stage although higher Braak stages were noted with focal more than with generalized epilepsy syndromes (P < 0.01). In 30% of patients, there was pathological evidence of traumatic brain injury that was significantly associated with higher Braak stages (P < 0.001). Cerebrovascular disease present in 40.3% and cortical malformations in 11.3% were not significantly associated with Braak stage. Astrocytic-tau protein correlated with the presence of both traumatic brain injury (P < 0.01) and high Braak stage (P < 0.001). Hippocampal sclerosis, identified in 40% (bilateral in 48%), was not associated with higher Braak stages, but asymmetrical patterns of tau protein accumulation within the sclerotic hippocampus were noted. In over half of patients with cognitive decline, the Braak stage was low indicating causes other than Alzheimer's disease pathology. In summary

  12. Analysis of death in major trauma: value of prompt post mortem computed tomography (pmCT) in comparison to office hour autopsy.

    Science.gov (United States)

    Schmitt-Sody, Markus; Kurz, Stefanie; Reiser, Maximilian; Kanz, Karl Georg; Kirchhoff, Chlodwig; Peschel, Oliver; Kirchhoff, Sonja

    2016-03-29

    To analyze diagnostic accuracy of prompt post mortem Computed Tomography (pmCT) in determining causes of death in patients who died during trauma room management and to compare the results to gold standard autopsy during office hours. Multiple injured patients who died during trauma room care were enrolled. PmCT was performed immediately followed by autopsy during office hours. PmCT and autopsy were analyzed primarily regarding pmCT ability to find causes of death and secondarily to define exact causes of death including accurate anatomic localizations. For the secondary analysis data was divided in group-I with equal results of pmCT and autopsy, group-II with autopsy providing superior results and group-III with pmCT providing superior information contributing to but not majorly causing death. Seventeen multiple trauma patients were enrolled. Since multiple trauma patients were enrolled more injuries than patients are provided. Eight patients sustained deadly head injuries (47.1%), 11 chest (64.7%), 4 skeletal system (23.5%) injuries and one patient drowned (5.8%). Primary analysis revealed in 16/17 patients (94.1%) causes of death in accordance with autopsy. Secondary analysis revealed in 9/17 cases (group-I) good agreement of autopsy and pmCT. In seven cases autopsy provided superior results (group-II) whereas in 1 case pmCT found more information (group-III). The presented work studied the diagnostic value of pmCT in defining causes of death in comparison to standard autopsy. Primary analysis revealed that in 94.1% of cases pmCT was able to define causes of death even if only indirect signs were present. Secondary analysis showed that pmCT and autopsy showed equal results regarding causes of death in 52.9%. PmCT is useful in traumatic death allowing for an immediate identification of causes of death and providing detailed information on bony lesions, brain injuries and gas formations. It is advisable to conduct pmCT especially in cases without consent to

  13. 76 FR 38668 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-07-01

    ...] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General.... In response to feedback during the April 13, 2010, Advisory Committee for Pharmaceutical Science and...

  14. 76 FR 38188 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-06-29

    ...] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General..., 2011, the committee will discuss current strategies for FDA's Office of Pharmaceutical Science...

  15. 75 FR 11551 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-03-11

    ...] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General... Pharmaceutical Science (OPS) on the regulatory challenges of drug-induced phospholipidosis (excessive...

  16. 78 FR 58315 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-09-23

    ...] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General... continuous manufacturing for pharmaceutical products. Speakers from the Agency, academia, and industry will...

  17. A Comparison of Sacroiliac and Pubic Rami Fracture Occurrences in Oblique Side Impact Tests on Nine Post Mortem Human Subjects.

    Science.gov (United States)

    Petit, Philippe; Trosseille, Xavier; Lebarbé, Mathieu; Baudrit, Pascal; Potier, Pascal; Compigne, Sabine; Masuda, Mitsutoshi; Yamaoka, Akira; Yasuki, Tsuyoshi; Douard, Richard

    2015-11-01

    The WorldSID dummy can be equipped with both a pubic and a sacroiliac joint (S-I joint) loadcell. Although a pubic force criterion and the associated injury risk curve are currently available and used in regulation (ECE95, FMVSS214), as of today injury mechanisms, injury criteria, and injury assessment reference values are not available for the sacroiliac joint itself. The aim of this study was to investigate the sacroiliac joint injury mechanism. Three configurations were identified from full-scale car crashes conducted with the WorldSID 50th percentile male where the force passing through the pubis in all three tests was approximately 1500 N while the sacroiliac Fy/Mx peak values were 4500 N/50 Nm, 2400 N/130 Nm, and 5300 N/150 Nm, respectively. These tests were reproduced using a 150 kg guided probe impacting Post Mortem Human Subjects (PMHS) at 8 m/s, 5.4 m/s and 7.5 m/s. The shape and the orientation of the impacting face of the probe were selected to match the WorldSID pubic Fy and sacroiliac Fy/Mx loads of the three vehicle test configurations. Three PMHS were tested in each of the three configurations (nine PMHS in total). In the first PMHS configuration, one specimen sustained an AIS 3 injury and one sustained an AIS 4 injury (an unstable pelvis with complete disruption of the posterior arch, a sacroiliac joint disruption associated with an iliac fracture, and a pubic symphysis separation). In the second configuration, all specimens sustained a fracture of the superior lateral iliac wing (AIS 2). In the third configuration, one specimen sustained a partial disruption of the anterior arch (AIS 2). Based on the data from strain gauges located on the pubic rami and near the sacroiliac joint, the pubic rami fractures were identified as occurring prior to the sacroiliac fractures. Out of nine impactor tests performed, the PMHS S-I joint injuries were observed to consistently be associated with pelvic anterior arch fractures. In addition, from the injury

  18. Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review

    Science.gov (United States)

    Hopperton, K E; Mohammad, D; Trépanier, M O; Giuliano, V; Bazinet, R P

    2018-01-01

    Neuroinflammation is proposed as one of the mechanisms by which Alzheimer’s disease pathology, including amyloid-β plaques, leads to neuronal death and dysfunction. Increases in the expression of markers of microglia, the main neuroinmmune cell, are widely reported in brains from patients with Alzheimer’s disease, but the literature has not yet been systematically reviewed to determine whether this is a consistent pathological feature. A systematic search was conducted in Medline, Embase and PsychINFO for articles published up to 23 February 2017. Papers were included if they quantitatively compared microglia markers in post-mortem brain samples from patients with Alzheimer’s disease and aged controls without neurological disease. A total of 113 relevant articles were identified. Consistent increases in markers related to activation, such as major histocompatibility complex II (36/43 studies) and cluster of differentiation 68 (17/21 studies), were identified relative to nonneurological aged controls, whereas other common markers that stain both resting and activated microglia, such as ionized calcium-binding adaptor molecule 1 (10/20 studies) and cluster of differentiation 11b (2/5 studies), were not consistently elevated. Studies of ionized calcium-binding adaptor molecule 1 that used cell counts almost uniformly identified no difference relative to control, indicating that increases in activation occurred without an expansion of the total number of microglia. White matter and cerebellum appeared to be more resistant to these increases than other brain regions. Nine studies were identified that included high pathology controls, patients who remained free of dementia despite Alzheimer’s disease pathology. The majority (5/9) of these studies reported higher levels of microglial markers in Alzheimer’s disease relative to controls, suggesting that these increases are not solely a consequence of Alzheimer’s disease pathology. These results show that

  19. Conductometric titration to determine total volatile basic nitrogen (TVB-N) for post-mortem interval (PMI).

    Science.gov (United States)

    Xia, Zhiyuan; Zhai, Xiandun; Liu, Beibei; Mo, Yaonan

    2016-11-01

    Precise measurement of cadaver decomposition rate is the basis to accurate post-mortem interval (PMI) estimation. There are many approaches explored in recent years, however, it is still unsolved completely. Total volatile basic nitrogen (TVB-N), which is an important index to predict meat freshness and shelf life in food science, could serve as an indicator for measuring PMI associated decomposition rate of cadavers. The aim of this work was to establish a practical method to determine TVB-N in cadaver soft tissues (mainly skeletal muscle) for measuring decomposition rate. Determination of TVB-N in the simulation and animal experiments was conducted by steam distillation and conductometric titration using Kjeldahl distillation unit and conductivity meter. In simulation, standard concentrations of ammonium were used as TVB analogies, TVB-N contents were determined and the recovery rates of nitrogen were calculated. In animal experiment, TVB-N in skeletal muscle of forty-two rats was determined at different PMIs for 312 h at 24 °C ± 1 °C. The relationship between PMI and TVB-N was investigated also. The method showed high precision with 99%-100% recovery rates. TVB-N in skeletal muscle changed significantly with PMI especially after 24 h, and the data fit well to y = 3.35 E -5 x 3 -2.17 E -2 x 2 +6.13x-85.82 (adj. R 2  = 0.985). EC i (initial electrical conductivity in the samples just before titration) had positive linear relationship to final measured TVB-N values, y = 1.98x+16.16 (adj. R 2  = 0.985). The overall results demonstrated that the method is accurate, rapid and flexible, which could be expected as a basic technique for measuring decomposition rate in later PMI-estimation researches. Further studies are needed to validate our findings. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  20. Clinical pharmacology profile of vorinostat, a histone deacetylase inhibitor.

    Science.gov (United States)

    Iwamoto, Marian; Friedman, Evan J; Sandhu, Punam; Agrawal, Nancy G B; Rubin, Eric H; Wagner, John A

    2013-09-01

    Vorinostat is a histone deacetylase inhibitor that has demonstrated preclinical activity in numerous cancer models. Clinical activity has been demonstrated in patients with a variety of malignancies. Vorinostat is presently indicated for the treatment of patients with advanced cutaneous T cell lymphoma (CTCL). Clinical investigation is ongoing for therapy of other solid tumors and hematological malignancies either as monotherapy or in combination with other chemotherapeutic agents. This review summarizes the pharmacokinetic properties of vorinostat. Monotherapy pharmacokinetic data across a number of pharmacokinetic studies were reviewed, and data are presented. In addition, literature review was performed to obtain published Phase I and II pharmacokinetic combination therapy data to identify and characterize potential drug interactions with vorinostat. Pharmacokinetic data in special populations were also reviewed. The clinical pharmacology profile of vorinostat is favorable, exhibiting dose-proportional pharmacokinetics and modest food effect. There appear to be no major differences in the pharmacokinetics of vorinostat in special populations, including varying demographics and hepatic dysfunction. Combination therapy pharmacokinetic data indicate that vorinostat has a low propensity for drug interactions. Vorinostat's favorable clinical pharmacology and drug interaction profile aid in the ease of administration of vorinostat for the treatment of advanced CTCL and will be beneficial in continued assessment for other oncologic indications. Although a number of studies have been conducted to elucidate the detailed pharmacokinetic profile of vorinostat, more rigorous assessment of vorinostat pharmacokinetics, including clinical drug interaction studies, will be informative.

  1. Clinical Pharmacology in Denmark in 2016 - 40 Years with the Danish Society of Clinical Pharmacology and 20 Years as a Medical Speciality

    DEFF Research Database (Denmark)

    Brøsen, Kim; Andersen, Stig Ejdrup; Borregaard, Jeanett

    2016-01-01

    new jobs and career opportunities for clinical pharmacologists. As of July 2016, the Danish Society of Clinical Pharmacology has 175 members, and 70 of these are specialists in clinical pharmacology corresponding to approximately 2.5 specialists per 1000 doctors (Denmark has in total 28,000 doctors...

  2. Phosphatidylcholine 36:1 concentration decreases along with demyelination in the cuprizone animal model and post-mortem of multiple sclerosis brain tissue.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Hildebrand, Kayla D; Nyamoya, Stella D; Amor, Sandra; Bazinet, Richard P; Kipp, Markus

    2018-03-25

    Multiple sclerosis (MS) is a demyelinating and inflammatory disease. Myelin is enriched in lipids, and more specifically, oleic acid. The goal of this study was to evaluate the concentration of oleic acid following demyelination and remyelination in the cuprizone model, test if these changes occurred in specific lipid species, and whether differences in the cuprizone model correlate with changes observed in post-mortem human brains. Eight-week-old C57Bl/6 mice were fed a 0.2% cuprizone diet for 5 weeks and some animals allowed to recover for 11 days. Demyelination, inflammation, and lipid concentrations were measured in the corpus callosum. Standard fatty acid techniques and liquid chromatography combined with tandem mass spectrometry were performed to measure concentrations of fatty acids in total brain lipids and a panel of lipid species within the phosphatidylcholine (PC). Similar measurements were conducted in post-mortem brain tissues of MS patients and were compared to healthy controls. Five weeks of cuprizone administration resulted in demyelination followed by significant remyelination after 11 days of recovery. Compared to control, oleic acid was decreased after 5 weeks of cuprizone treatment and increased during the recovery phase. This decrease in oleic acid was associated with a specific decrease in the PC 36:1 pool. Similar results were observed in human post-mortem brains. Decreases in myelin content in the cuprizone model was accompanied with decreases in oleic acid concentration and is associated with PC 36:1 suggesting that specific lipids could be a potential biomarker for myelin degeneration. The biological relevance of oleic acid for disease progression remains to be verified. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. Role of biogenic amines in the post-mortem migration of Anisakis pegreffii (Nematoda: Anisakidae Dujardin, 1845) larvae into fish fillets.

    Science.gov (United States)

    Šimat, Vida; Miletić, Jelena; Bogdanović, Tanja; Poljak, Vedran; Mladineo, Ivona

    2015-12-02

    Infective third-stage larvae (L3) of nematode Anisakis spp. have been recognized as one of the major food-borne threats in lightly processed fish products in Europe, particularly in the Mediterranean region. Therefore, the effect of different storage temperatures of fish on larval post-mortem migration from visceral cavity into fillets is an important parameter to take into account when evaluating the risk for consumer safety. The European anchovy (Engraulis encrasicolus) were caught during fishing season, a subsample of fillets was checked for the presence of Anisakis larvae at capture (mean abundance=0.07), and the rest was stored at four different temperatures (-18, 0, 4 and 22°C) in order to count migrating larvae and measure the production of biogenic amines over a period of time. Larvae were identified by morphological features and molecular tools. Post-mortem migration was observed in fillets stored at 0 and 4°C after three and five days, respectively, but not at 22 and -18°C. In case of storage at 22°C for two days, at the onset of putrefaction of the visceral organs, larvae migrated out of the visceral cavity towards the fish surface. Measured pH and biogenic amine profile during storage indicated that certain biochemical conditions trigger larval migration into fillets. Likewise, migration was observed at pH ~6.4 when sensory degradation of the fish was markedly visible. Although larval migration was delayed for approximately four days at a temperature of fillet was high and statistically significant at both 0 (r=0.998, p<0.01) and 4°C (r=0.946, p<0.05). Out of eight biogenic amines measured, cadaverine and putrescine levels correlated the most with the post-mortem migration at 4°C, while tyramine levels were significant at both temperatures. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Amphetamine, past and present--a pharmacological and clinical perspective.

    Science.gov (United States)

    Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-06-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine's diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine's distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.

  5. Amphetamine, past and present – a pharmacological and clinical perspective

    Science.gov (United States)

    Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-01-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine’s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed. PMID:23539642

  6. Tissues from equine cadaver ligaments up to 72 hours of post-mortem: a promising reservoir of stem cells.

    Science.gov (United States)

    Shikh Alsook, Mohamad Khir; Gabriel, Annick; Piret, Joëlle; Waroux, Olivier; Tonus, Céline; Connan, Delphine; Baise, Etienne; Antoine, Nadine

    2015-12-18

    Mesenchymal stem cells (MSCs) harvested from cadaveric tissues represent a promising approach for regenerative medicine. To date, no study has investigated whether viable MSCs could survive in cadaveric tissues from tendon or ligament up to 72 hours of post-mortem. The purpose of the present work was to find out if viable MSCs could survive in cadaveric tissues from adult equine ligaments up to 72 hours of post-mortem, and to assess their ability (i) to remain in an undifferentiated state and (ii) to divide and proliferate in the absence of any specific stimulus. MSCs were isolated from equine cadaver (EC) suspensory ligaments within 48-72 hours of post-mortem. They were evaluated for viability, proliferation, capacity for tri-lineage differentiation, expression of cell surface markers (CD90, CD105, CD73, CD45), pluripotent transcription factor (OCT-4), stage-specific embryonic antigen-1 (SSEA-1), neuron-specific class III beta-tubulin (TUJ-1), and glial fibrillary acidic protein (GFAP). As well, they were characterized by transmission electron microscope (TEM). EC-MSCs were successfully isolated and maintained for 20 passages with high cell viability and proliferation. Phase contrast microscopy revealed that cells with fibroblast-like appearance were predominant in the culture. Differentiation assays proved that EC-MSCs are able to differentiate towards mesodermal lineages (osteogenic, adipogenic, chondrogenic). Flow cytometry analysis demonstrated that EC-MSCs expressed CD90, CD105, and CD73, while being negative for the leukocyte common antigen CD45. Immunofluorescence analysis showed a high percentage of positive cells for OCT-4 and SSEA-1. Surprisingly, in absence of any stimuli, some adherent cells closely resembling neuronal and glial morphology were also observed. Interestingly, our results revealed that approximately 15 % of the cell populations were TUJ-1 positive, whereas GFAP expression was detected in only a few cells. Furthermore, TEM analysis

  7. An audit of the contribution to post-mortem examination diagnosis of individual analyte results obtained from biochemical analysis of the vitreous.

    Science.gov (United States)

    Mitchell, Rebecca; Charlwood, Cheryl; Thomas, Sunethra Devika; Bellis, Maria; Langlois, Neil E I

    2013-12-01

    Biochemical analysis of the vitreous humor from the eye is an accepted accessory test for post-mortem investigation of cause of death. Modern biochemical analyzers allow testing of a range of analytes from a sample. However, it is not clear which analytes should be requested in order to prevent unnecessary testing (and expense). The means and standard deviation of the values obtained from analysis of the vitreous humor for sodium, potassium, chloride, osmolality, glucose, ketones (β-hydroxybutyrate), creatinine, urea, calcium, lactate, and ammonia were calculated from which the contribution of each analyte was reviewed in the context of post-mortem findings and final cause of death. For sodium 32 cases were regarded as high (more than one standard deviation above the mean), from which 9 contributed to post-mortem diagnosis [drowning (4), heat related death (2), diabetic hyperglycemia (2), and dehydration (1)], but 25 low values (greater than one standard deviation below the mean) made no contribution. For chloride 29 high values contributed to 4 cases--3 drowning and 1 heat-related, but these were all previously identified by a high sodium level. There were 29 high and 35 low potassium values, none of which contributed to determining the final cause of death. Of 22 high values of creatinine, 12 contributed to a diagnosis of renal failure. From 32 high values of urea, 18 contributed to 16 cases of renal failure (2 associated with diabetic hyperglycemia), 1 heat-related death, and one case with dehydration. Osmolarity contributed to 12 cases (5 heat-related, 4 diabetes, 2 renal failure, and 1 dehydration) from 36 high values. There was no contribution from 32 high values and 19 low values of calcium and there was no contribution from 4 high and 2 low values of ammonia. There were 11 high values of glucose, which contributed to the diagnosis of 6 cases of diabetic hyperglycemia and 21 high ketone levels contributed to 8 cases: 4 diabetic ketosis, 3 hypothermia, 3

  8. Approach to pharmacological and clinical applications of Anisi aetheroleum

    Directory of Open Access Journals (Sweden)

    Khaled Mohamed Mohamed Koriem

    2015-01-01

    Full Text Available Anisi aetheroleum is the oil obtained from Pimpinella anisum L. (P. anisum by steam distillation. P. anisum seeds were air-dried, and then the dry seeds were crushed, pulverized, and weighed in sequence for anise oil preparation. P. anisum is one of the oldest medicinal plants that belong to family Apiaceae. The fruit of P. anisum is harvested in August and September. P. anisum is widespread in Asia, Africa and Europe. Local names of P. anisum include anise, anisoon, roomy, saunf, sweet cumin and yansoon. The anise oil odour is aromatic while the oil tastes sweet. The average daily dose of Anisi aetheroleum is 0.3 g. trans-Anethole is the major ingredient of the anise oil. Anisi aetheroleum also displays a protective action against neurotoxicity. In addition, Anisi aetheroleum increases glucose absorption and reduces urine output in the rat. The plant oil have pharmacological (antimicrobial, hepatoprotective, anticonvulsant, anti-inflammatory, antispasmodic, bronchodilator, estrogenic, expectorant and insecticidal effects and clinical effects on nausea, constipation, menopausal period, virus, diabetes, obesity and sedative action. Owing to the wide application of Anisi aetheroleum in pharmacological and clinical fields, it is recommended for more clinical trails to discover a new medication from the active constituents of the plant oil in the future to treat human diseases especially chronic ones.

  9. Pharmacological effect on pyeloureteric dynamics with a clinical perspective

    DEFF Research Database (Denmark)

    Jung, Helene U; Frimodt-Møller, Poul C; Osther, Palle J

    2006-01-01

    We searched to review experimental and clinical trials concerning the capabilities of impacting on the ureteric and pelvic activity by means of pharmacological stimulation. Ureteropyeloscopy may cause high renal pelvic pressure. The normal pressure is in the range of 5-15 mmHg whereas pressure...... an increased risk of several complications related to endourological procedures including bleeding, perforation and infection. In other words, means by which intrarenal pressure could be lowered during endourological procedures might be beneficial with respect to clinical outcomes. In vitro experiments support...... systemic side effects. In vivo human studies are necessary to clarify the exact dose-response relationship and the degree of urothelial absorption of a drug before clinical use may be adopted....

  10. Male and female WorldSID and post mortem human subject responses in full-scale vehicle tests.

    Science.gov (United States)

    Yoganandan, Narayan; Humm, John; Pintar, Frank; Rhule, Heather; Moorhouse, Kevin; Suntay, Brian; Stricklin, Jim; Rudd, Rodney; Craig, Matthew

    2017-05-29

    This study compares the responses of male and female WorldSID dummies with post mortem human subject (PMHS) responses in full-scale vehicle tests. Tests were conducted according to the FMVSS-214 protocols and using the U.S. Side Impact New Car Assessment Program change in velocity to match PMHS experiments, published earlier. Moving deformable barrier (MDB) tests were conducted with the male and female surrogates in the left front and left rear seats. Pole tests were performed with the male surrogate in the left front seat. Three-point belt restraints were used. Sedan-type vehicles were used from the same manufacturer with side airbags. The PMHS head was instrumented with a pyramid-shaped nine-axis accelerometer package, with angular velocity transducers on the head. Accelerometers and angular velocity transducers were secured to T1, T6, and T12 spinous processes and sacrum. Three chest bands were secured around the upper, middle, and lower thoraces. Dummy instrumentation included five infrared telescoping rods for assessment of chest compression (IR-TRACC) and a chest band at the first abdomen rib, head angular velocity transducer, and head, T1, T4, T12, and pelvis accelerometers. Morphological responses of the kinematics of the head, thoracic spine, and pelvis matched in both surrogates for each pair. The peak magnitudes of the torso accelerations were lower for the dummy than for the biological surrogate. The brain rotational injury criterion (BrIC) response was the highest in the male dummy for the MDB test and PMHS. The probability of AIS3+ injuries, based on the head injury criterion, ranged from 3% to 13% for the PMHS and from 3% to 21% for the dummy from all tests. The BrIC-based metrics ranged from 0 to 21% for the biological and 0 to 48% for the dummy surrogates. The deflection profiles from the IR-TRACC sensors were unimodal. The maximum deflections from the chest band placed on the first abdominal rib were 31.7 mm and 25.4 mm for the male and female

  11. Longitudinal assessment of short-term memory deterioration in a logopenic variant primary progressive aphasia with post-mortem confirmed Alzheimer's Disease pathology.

    Science.gov (United States)

    Tree, Jeremy; Kay, Janice

    2015-09-01

    In the field of dementia research, there are reports of neurodegenerative cases with a focal loss of language, termed primary progressive aphasia (PPA). Currently, this condition has been further sub-classified, with the most recent sub-type dubbed logopenic variant (PPA-LV). As yet, there remains somewhat limited evaluation of the characteristics of this condition, with no studies providing longitudinal assessment accompanied by post-mortem examination. Moreover, a key characteristic of the PPA-LV case is a deterioration of phonological short-term memory, but again little work has scrutinized the nature of this impairment over time. The current study seeks to redress these oversights and presents detailed longitudinal examination of language and memory function in a case of PPA-LV, with special focus on tests linked to components of phonological short-term memory function. Our findings are then considered with reference to a contemporary model of the neuropsychology of phonological short-term memory. Additionally, post-mortem examinations indicated Alzheimer's disease type pathology, providing further evidence that the PPA-LV presentation may reflect an atypical presentation of this condition. © 2014 The British Psychological Society.

  12. Reflexiones Acerca del Papel de la Mujer en la Reproducción Artificial Post Mortem (Analysis of the Role of Women in the Posthumous Reproduction

    Directory of Open Access Journals (Sweden)

    Alma Marìa Rodrìguez Guitián

    2017-03-01

    Full Text Available This contribution focuses on the analysis of the role of women in the posthumous reproduction. In the first place, it studies whether the woman's right to have children should be subject to limits and, if so, to which ones. Second, it explores if the posthumous reproduction extends to lesbian couples, married or not, and finally it focuses on the relevance of the mother's will to decide the deceased to be registered as the parent of the child. Este trabajo tiene por objeto el análisis del papel de la mujer en la hipótesis de la reproducción artificial post mortem. En primer lugar, aborda si el derecho a procrear de la mujer está sujeto a límites y, si es así, cuáles son. En segundo lugar, si la reproducción artificial post mortem se extiende desde el punto de vista subjetivo al matrimonio y parejas de mujeres y, por último, cuál es la relevancia de la voluntad de la madre gestante a la hora de decidir la determinación de la paternidad o maternidad de la persona fallecida. DOWNLOAD THIS PAPER FROM SSRN: https://ssrn.com/abstract=2921870

  13. Degradation of Kidney and Psoas Muscle Proteins as Indicators of Post-Mortem Interval in a Rat Model, with Use of Lateral Flow Technology.

    Directory of Open Access Journals (Sweden)

    Dong-Gi Lee

    Full Text Available We investigated potential protein markers of post-mortem interval (PMI using rat kidney and psoas muscle. Tissue samples were taken at 12 h intervals for up to 96 h after death by suffocation. Expression levels of eight soluble proteins were analyzed by Western blotting. Degradation patterns of selected proteins were clearly divided into three groups: short-term, mid-term, and long-term PMI markers based on the half maximum intensity of intact protein expression. In kidney, glycogen synthase (GS and glycogen synthase kinase-3β were degraded completely within 48 h making them short-term PMI markers. AMP-activated protein kinase α, caspase 3 and GS were short-term PMI markers in psoas muscle. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH was a mid-term PMI marker in both tissues. Expression levels of the typical long-term PMI markers, p53 and β-catenin, were constant for at least 96 h post-mortem in both tissues. The degradation patterns of GS and caspase-3 were verified by immunohistochemistry in both tissues. GAPDH was chosen as a test PMI protein to perform a lateral flow assay (LFA. The presence of recombinant GAPDH was clearly detected in LFA and quantified in a concentration-dependent manner. These results suggest that LFA might be used to estimate PMI at a crime scene.

  14. Ablation of fast-spiking interneurons in the dorsal striatum, recapitulating abnormalities seen post-mortem in Tourette syndrome, produces anxiety and elevated grooming.

    Science.gov (United States)

    Xu, M; Li, L; Pittenger, C

    2016-06-02

    Tic disorders, including Tourette syndrome (TS), are thought to involve pathology of cortico-basal ganglia loops, but their pathology is not well understood. Post-mortem studies have shown a reduced number of several populations of striatal interneurons, including the parvalbumin-expressing fast-spiking interneurons (FSIs), in individuals with severe, refractory TS. We tested the causal role of this interneuronal deficit by recapitulating it in an otherwise normal adult mouse using a combination transgenic-viral cell ablation approach. FSIs were reduced bilaterally by ∼40%, paralleling the deficit found post-mortem. This did not produce spontaneous stereotypies or tic-like movements, but there was increased stereotypic grooming after acute stress in two validated paradigms. Stereotypy after amphetamine, in contrast, was not elevated. FSI ablation also led to increased anxiety-like behavior in the elevated plus maze, but not to alterations in motor learning on the rotorod or to alterations in prepulse inhibition, a measure of sensorimotor gating. These findings indicate that a striatal FSI deficit can produce stress-triggered repetitive movements and anxiety. These repetitive movements may recapitulate aspects of the pathophysiology of tic disorders. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Dissecting the pathobiology of altered MRI signal in amyotrophic lateral sclerosis: A post mortem whole brain sampling strategy for the integration of ultra-high-field MRI and quantitative neuropathology.

    Science.gov (United States)

    Pallebage-Gamarallage, Menuka; Foxley, Sean; Menke, Ricarda A L; Huszar, Istvan N; Jenkinson, Mark; Tendler, Benjamin C; Wang, Chaoyue; Jbabdi, Saad; Turner, Martin R; Miller, Karla L; Ansorge, Olaf

    2018-03-13

    Amyotrophic lateral sclerosis (ALS) is a clinically and histopathologically heterogeneous neurodegenerative disorder, in which therapy is hindered by the rapid progression of disease and lack of biomarkers. Magnetic resonance imaging (MRI) has demonstrated its potential for detecting the pathological signature and tracking disease progression in ALS. However, the microstructural and molecular pathological substrate is poorly understood and generally defined histologically. One route to understanding and validating the pathophysiological correlates of MRI signal changes in ALS is to directly compare MRI to histology in post mortem human brains. The article delineates a universal whole brain sampling strategy of pathologically relevant grey matter (cortical and subcortical) and white matter tracts of interest suitable for histological evaluation and direct correlation with MRI. A standardised systematic sampling strategy that was compatible with co-registration of images across modalities was established for regions representing phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) patterns that were topographically recognisable with defined neuroanatomical landmarks. Moreover, tractography-guided sampling facilitated accurate delineation of white matter tracts of interest. A digital photography pipeline at various stages of sampling and histological processing was established to account for structural deformations that might impact alignment and registration of histological images to MRI volumes. Combined with quantitative digital histology image analysis, the proposed sampling strategy is suitable for routine implementation in a high-throughput manner for acquisition of large-scale histology datasets. Proof of concept was determined in the spinal cord of an ALS patient where multiple MRI modalities (T1, T2, FA and MD) demonstrated sensitivity to axonal degeneration and associated heightened inflammatory changes in the lateral corticospinal tract. Furthermore

  16. Drug repurposing: translational pharmacology, chemistry, computers and the clinic.

    Science.gov (United States)

    Issa, Naiem T; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2013-01-01

    The process of discovering a pharmacological compound that elicits a desired clinical effect with minimal side effects is a challenge. Prior to the advent of high-performance computing and large-scale screening technologies, drug discovery was largely a serendipitous endeavor, as in the case of thalidomide for erythema nodosum leprosum or cancer drugs in general derived from flora located in far-reaching geographic locations. More recently, de novo drug discovery has become a more rationalized process where drug-target-effect hypotheses are formulated on the basis of already known compounds/protein targets and their structures. Although this approach is hypothesis-driven, the actual success has been very low, contributing to the soaring costs of research and development as well as the diminished pharmaceutical pipeline in the United States. In this review, we discuss the evolution in computational pharmacology as the next generation of successful drug discovery and implementation in the clinic where high-performance computing (HPC) is used to generate and validate drug-target-effect hypotheses completely in silico. The use of HPC would decrease development time and errors while increasing productivity prior to in vitro, animal and human testing. We highlight approaches in chemoinformatics, bioinformatics as well as network biopharmacology to illustrate potential avenues from which to design clinically efficacious drugs. We further discuss the implications of combining these approaches into an integrative methodology for high-accuracy computational predictions within the context of drug repositioning for the efficient streamlining of currently approved drugs back into clinical trials for possible new indications.

  17. Clinical pharmacology profile of care in Hepatology clinic

    Directory of Open Access Journals (Sweden)

    Talita Rocha Passos

    Full Text Available Summary Since 2010, the Clinical Gastroenterology and Hepatology Division of the Central Institute of Hospital das Clínicas of the University of São Paulo Medical School (HC-FMUSP, in the Portuguese acronym has been developing specialized electives assistance activities in the Outpatient Specialty Clinic, Secondary Level, in São Paulo NGA-63 Várzea do Carmo. The objective of this study was to analyze the pharmacotherapeutic profile of patients. This is a cross-sectional and retrospective study in which patients were seen at the Hepatology sector and the results were submitted to descriptive statistics. During the study period, 492 patients were treated at the clinic, with a mean age of 58.9 years and frequency of 61.2% female and 74.8% living in São Paulo. This population was served by various other medical specialties (cardiology and endocrine among others and the major liver diagnoses were: chronic hepatitis B and C and fatty liver. Comorbidities were also identified, such as diabetes, hypertension and dyslipidemia. Most patients took their medication in the Basic Health Units. We found that 30% of patients use of more than five medications and the most prescribed were omeprazole 208 (42.3%, metformin 132 (26.8% and losartan 80 (16.3%. Because it is an adult/elderly population, with several comorbidities and polymedication, it is important to be aware of the rational use of medication. The multidisciplinary team is important in applying correct conducts for the safe use of medicines, to reduce the burden on health spending and improving the quality of life of patients.

  18. World Antimalarial Resistance Network (WARN IV: Clinical pharmacology

    Directory of Open Access Journals (Sweden)

    Gbotosho Grace O

    2007-09-01

    Full Text Available Abstract A World Antimalarial Resistance Network (WARN database has the potential to improve the treatment of malaria, through informing current drug selection and use and providing a prompt warning of when treatment policies need changing. This manuscript outlines the contribution and structure of the clinical pharmacology component of this database. The determinants of treatment response are multi-factorial, but clearly providing adequate blood concentrations is pivotal to curing malaria. The ability of available antimalarial pharmacokinetic data to inform optimal dosing is constrained by the small number of patients studied, with even fewer (if any studies conducted in the most vulnerable populations. There are even less data relating blood concentration data to the therapeutic response (pharmacodynamics. By pooling all available pharmacokinetic data, while paying careful attention to the analytical methodologies used, the limitations of small (and thus underpowered individual studies may be overcome and factors that contribute to inter-individual variability in pharmacokinetic parameters defined. Key variables for pharmacokinetic studies are defined in terms of patient (or study subject characteristics, the formulation and route of administration of the antimalarial studied, the sampling and assay methodology, and the approach taken to data analysis. Better defining these information needs and criteria of acceptability of pharmacokinetic-pharmacodynamic (PK-PD studies should contribute to improving the quantity, relevance and quality of these studies. A better understanding of the pharmacokinetic properties of antimalarials and a more clear definition of what constitutes "therapeutic drug levels" would allow more precise use of the term "antimalarial resistance", as it would indicate when treatment failure is not caused by intrinsic parasite resistance but is instead the result of inadequate drug levels. The clinical pharmacology component

  19. Clinical and practical considerations in the pharmacologic management of narcolepsy.

    Science.gov (United States)

    Thorpy, Michael J; Dauvilliers, Yves

    2015-01-01

    Despite published treatment recommendations and the availability of approved and off-label pharmacologic therapies for narcolepsy, the clinical management of this incurable, chronic neurologic disorder remains challenging. While treatment is generally symptomatically driven, decisions regarding which drug(s) to use need to take into account a variety of factors that may affect adherence, efficacy, and tolerability. Type 1 narcolepsy (predominantly excessive daytime sleepiness with cataplexy) or type 2 narcolepsy (excessive daytime sleepiness without cataplexy) may drive treatment decisions, with consideration given either to a single drug that targets multiple symptoms or to multiple drugs that each treat a specific symptom. Other drug-related characteristics that affect drug choice are dosing regimens, tolerability, and potential drug-drug interactions. Additionally, the patient should be an active participant in treatment decisions, and the main symptomatic complaints, treatment goals, psychosocial setting, and use of lifestyle substances (ie, alcohol, nicotine, caffeine, and cannabis) need to be discussed with respect to treatment decisions. Although there is a lack of narcolepsy-specific instruments for monitoring therapeutic effects, clinically relevant subjective and objective measures of daytime sleepiness (eg, Epworth Sleepiness Scale and Maintenance of Wakefulness Test) can be used to provide guidance on whether treatment goals are being met. These considerations are discussed with the objective of providing clinically relevant recommendations for making treatment decisions that can enhance the effective management of patients with narcolepsy. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Influence of supplemental maslinic acid (olive-derived triterpene) on the post-mortem muscle properties and quality traits of gilthead seabream

    DEFF Research Database (Denmark)

    Matos, E.; Silva, Tomé Santos; Wulff, Tune

    2013-01-01

    , enzymatic activities and protein expression in the muscle were assessed. Supplementing gilthead seabream diets with maslinic acid mainly resulted in hypertrophy of muscle fibres and inhibition of cathepsin B activity, with no observed differences in terms of glycogen and ATP content of the muscle, as well...... as glycogen phosphorylase activity. Proteomic analysis showed a low impact of maslinic acid supplementation on muscle metabolism, with most changes reflecting increased stress coping capacity and muscle hypertrophy in maslinic acid-fed fish. As a finishing strategy to improve the muscle's energetic status......Maslinic acid, a natural triterpene, was evaluated as a dietary supplement to modulate glycogen post-mortem mobilization in gilthead seabream muscle. For this purpose, a multidisciplinary trial was undertaken, where flesh quality criteria, as well as biochemical and histological parameters...

  1. Evaluation of hypostasis using a colorimeter measuring system and its application to assessment of the post-mortem interval (time of death).

    Science.gov (United States)

    Vanezis, P; Trujillo, O

    1996-03-05

    Hypostasis was measured in 93 cadavers using a tristimulus colorimeter in order to investigate its relationship with the time of death. The intensity (lightness) of the hypostasis in each case was measured over a period of 4 h and the rate of change in lightness derived. When examined against the time of death, it was found that there was a good correlation between the two. Namely, that the rate of change of lightness (and it can be inferred that this represents displaceability) decreases as the post-mortem period increases. The shift in hypostasis was particularly marked in the first 12 h and decreased thereafter. However, hypostasis could be useful for time of death estimation for up to 48 h. After this time, the degree of change was small or non-existent and by 72 h hypostasis had become fixed in the majority of cases, within our measuring period of 4 h.

  2. Time to address the problem of post-mortem procurement of organs for transplantation occurring without proper pre-mortem consent.

    Science.gov (United States)

    Garwood-Gowers, Austen

    2013-09-01

    Current cadaveric organ transplant systems allow individuals to be classified as donors after death where they registered wishes in favour of this prior to death. However, systems for registering wishes pertaining to donation fall woefully short of securing proper consent. Furthermore, even jurisdictions which technically require consent to be obtained in order to treat an individual as a donor, allow that consent to be given by next of kin after death in circumstances where there is no evidence of the individual having refused prior to death. This article explores these and related issues with current systems from the perspectives of health law norms, ethics and human rights. It concludes that proper pre-mortem consent ought to be a pre-requisite for post-mortem organ transplantation.

  3. Microstructural parcellation of the human cerebral cortex – from Brodmann's post-mortem map to in vivo mapping with high-field magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Stefan Geyer

    2011-02-01

    Full Text Available The year 2009 marked the 100th anniversary of the publication of the famous brain map of Korbinian Brodmann. Although a "classic" guide to microanatomical parcellation of the cerebral cortex, it is – from today's state-of-the-art neuroimaging perspective – problematic to use Brodmann's map as a structural guide to functional units in the cortex. In this article we discuss some of the reasons, especially the problematic compatibility of the "post-mortem world" of microstructural brain maps with the "in vivo world" of neuroimaging. We conclude with some prospects for the future of in vivo structural brain mapping: a new approach which has the enormous potential to make direct correlations between microstructure and function in living human brains: "in vivo Brodmann mapping" with high-field magnetic resonance imaging.

  4. PMICALC: an R code-based software for estimating post-mortem interval (PMI) compatible with Windows, Mac and Linux operating systems.

    Science.gov (United States)

    Muñoz-Barús, José I; Rodríguez-Calvo, María Sol; Suárez-Peñaranda, José M; Vieira, Duarte N; Cadarso-Suárez, Carmen; Febrero-Bande, Manuel

    2010-01-30

    In legal medicine the correct determination of the time of death is of utmost importance. Recent advances in estimating post-mortem interval (PMI) have made use of vitreous humour chemistry in conjunction with Linear Regression, but the results are questionable. In this paper we present PMICALC, an R code-based freeware package which estimates PMI in cadavers of recent death by measuring the concentrations of potassium ([K+]), hypoxanthine ([Hx]) and urea ([U]) in the vitreous humor using two different regression models: Additive Models (AM) and Support Vector Machine (SVM), which offer more flexibility than the previously used Linear Regression. The results from both models are better than those published to date and can give numerical expression of PMI with confidence intervals and graphic support within 20 min. The program also takes into account the cause of death. 2009 Elsevier Ireland Ltd. All rights reserved.

  5. Clinical pharmacology review of escitalopram for the treatment of depression.

    Science.gov (United States)

    Pastoor, Devin; Gobburu, Joga

    2014-01-01

    Depression is a serious and debilitating psychiatric condition with serious societal health and economic implications. Escitalopram , the S-enantiomer of racemic citalopram, is an effective treatment for major depressive disorder. This review covers the clinical pharmacology of escitalopram, with emphasis on regulatory approval. Its pharmacokinetics, pharmacodynamics and clinical efficacy for major depressive disorder are evaluated, along with data regarding safety and tolerability. Drug development of escitalopram was heavily guided by prior approval of citalopram. Select safety and efficacy studies for escitalopram in combination with supportive evidence from the results of prior citalopram studies allowed for regulatory approval for acute and maintenance claims in both adults and adolescents, while minimizing burden on the sponsor. Escitalopram has been shown to have better efficacy and safety profile than other selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor drugs, including racemic citalopram. The first generic escitalopram was approved in 2012, along with Abbreviated New Drug Applications. The associated cost savings have helped reduce the burden of weighing the benefits of escitalopram over less-expensive alternatives.

  6. Post mortem scientific sampling and the search for causes of death in intensive care: what information should be given and what consent should be obtained?

    Science.gov (United States)

    Rigaud, J P; Quenot, J P; Borel, M; Plu, I; Hervé, C; Moutel, G

    2011-03-01

    The search for cause of death is important to improve knowledge and provide answers for the relatives of the deceased. Medical autopsy following unexplained death in hospital is one way to identify cause of death but is difficult to carry out routinely. Post mortem sampling (PMS) of tissues via thin biopsy needle or 'mini incisions' in the skin may be a useful alternative. A study was undertaken to assess how this approach is perceived by intensive care doctors and also to evaluate how this practice is considered in ethical terms in France. A study of PMS practices immediately after death in 10 intensive care departments was performed. The medical director of each centre was interviewed by telephone and asked to describe practices in their unit and to outline the questions raised by this practice. PMS is routinely performed in 70% of the units which responded, without systematically obtaining formal consent and without precise rules for communicating results. Approaches to PMS differed between centres, but all physicians felt that PMS is useful for the scientific information it gives and also for the information it provides for relatives. All physicians regret the lack of standards to structure PMS practices. Information from post mortem examinations is important for society to inform about causes of death, for doctors to improve practices and for decision-makers responsible for organising care. Debate persists regarding the balance between individual rights and community interests. It is suggested that an approach for identifying cause of death could easily be integrated into the relationship between carers and relatives, provided full transparency is maintained.

  7. HIF1α protein and mRNA expression as a new marker for post mortem interval estimation in human gingival tissue.

    Science.gov (United States)

    Fais, Paolo; Mazzotti, Maria Carla; Teti, Gabriella; Boscolo-Berto, Rafael; Pelotti, Susi; Falconi, Mirella

    2018-06-01

    Estimating the post mortem interval (PMI) is still a crucial step in Forensic Pathology. Although several methods are available for assessing the PMI, a precise estimation is still quite unreliable and can be inaccurate. The present study aimed to investigate the immunohistochemical distribution and mRNA expression of hypoxia inducible factor (HIF-1α) in post mortem gingival tissues to establish a correlation between the presence of HIF-1α and the time since death, with the final goal of achieving a more accurate PMI estimation. Samples of gingival tissues were obtained from 10 cadavers at different PMIs (1-3 days, 4-5 days and 8-9 days), and were processed for immunohistochemistry and quantitative reverse transcription-polymerase chain reaction. The results showed a time-dependent correlation of HIF-1α protein and its mRNA with different times since death, which suggests that HIF-1α is a potential marker for PMI estimation. The results showed a high HIF-1α protein signal that was mainly localized in the stratum basale of the oral mucosa in samples collected at a short PMI (1-3 days). It gradually decreased in samples collected at a medium PMI (4-5 days), but it was not detected in samples collected at a long PMI (8-9 days). These results are in agreement with the mRNA data. These data indicate an interesting potential utility of Forensic Anatomy-based techniques, such as immunohistochemistry, as important complementary tools to be used in forensic investigations. © 2018 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

  8. A semi-automated method for non-invasive internal organ weight estimation by post-mortem magnetic resonance imaging in fetuses, newborns and children

    International Nuclear Information System (INIS)

    Thayyil, Sudhin; Schievano, Silvia; Robertson, Nicola J.; Jones, Rodney; Chitty, Lyn S.; Sebire, Neil J.; Taylor, Andrew M.

    2009-01-01

    Magnetic resonance (MR) imaging allows minimally invasive autopsy, especially when consent is declined for traditional autopsy. Estimation of individual visceral organ weights is an important component of traditional autopsy. Objective: To examine whether a semi-automated can be used for non-invasive internal organ weight measurement using post-mortem MR imaging in fetuses, newborns and children. Methods: Phase 1: In vitro scanning of 36 animal organs (heart, liver, kidneys) was performed to check the accuracy of volume reconstruction methodology. Real volumes were measured by water displacement method. Phase 2: Sixty-five whole body post-mortem MR scans were performed in fetuses (n = 30), newborns (n = 5) and children (n = 30) at 1.5 T using a 3D TSE T2-weighted sequence. These data were analysed offline using the image processing software Mimics 11.0. Results: Phase 1: Mean difference (S.D.) between estimated and actual volumes were -0.3 (1.5) ml for kidney, -0.7 (1.3) ml for heart, -1.7 (3.6) ml for liver in animal experiments. Phase 2: In fetuses, newborns and children mean differences between estimated and actual weights (S.D.) were -0.6 (4.9) g for liver, -5.1 (1.2) g for spleen, -0.3 (0.6) g for adrenals, 0.4 (1.6) g for thymus, 0.9 (2.5) g for heart, -0.7 (2.4) g for kidneys and 2.7 (14) g for lungs. Excellent co-correlation was noted for estimated and actual weights (r 2 = 0.99, p < 0.001). Accuracy was lower when fetuses were less than 20 weeks or less than 300 g. Conclusion: Rapid, accurate and reproducible estimation of solid internal organ weights is feasible using the semi-automated 3D volume reconstruction method.

  9. Detection and differentiation of early acute and following age stages of myocardial infarction with quantitative post-mortem cardiac 1.5T MR.

    Science.gov (United States)

    Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J; Schuster, Frederick; Riva, Fabiano; Zech, Wolf-Dieter

    2017-01-01

    Recently, quantitative MR sequences have started being used in post-mortem imaging. The goal of the present study was to evaluate if early acute and following age stages of myocardial infarction can be detected and discerned by quantitative 1.5T post-mortem cardiac magnetic resonance (PMCMR) based on quantitative T1, T2 and PD values. In 80 deceased individuals (25 female, 55 male), a cardiac MR quantification sequence was performed prior to cardiac dissection at autopsy in a prospective study. Focal myocardial signal alterations detected in synthetically generated MR images were MR quantified for their T1, T2 and PD values. The locations of signal alteration measurements in PMCMR were targeted at autopsy heart dissection and cardiac tissue specimens were taken for histologic examinations. Quantified signal alterations in PMCMR were correlated to their according histologic age stage of myocardial infarction. In PMCMR seventy-three focal myocardial signal alterations were detected in 49 of 80 investigated hearts. These signal alterations were diagnosed histologically as early acute (n=39), acute (n=14), subacute (n=10) and chronic (n=10) age stages of myocardial infarction. Statistical analysis revealed that based on their quantitative T1, T2 and PD values, a significant difference between all defined age groups of myocardial infarction can be determined. It can be concluded that quantitative 1.5T PMCMR quantification based on quantitative T1, T2 and PD values is feasible for characterization and differentiation of early acute and following age stages of myocardial infarction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. "What happens behind the curtains?" An exploration of ICU nurses' experiences of post mortem care on patients who have died in intensive care.

    Science.gov (United States)

    de Swardt, Carien; Fouché, Nicola

    2017-12-01

    The aim of this study was to explore the experiences of intensive care nurses performing post mortem care on patients who had died in an intensive care unit at a private hospital in Cape Town. The study further sets out to identify educational needs and to offer recommendations that may address these needs for this sample of nurses. A qualitative research design using a descriptive method was used to explore the experiences of a purposive heterogeneous sample of six nurses who were working in an intensive care unit in a private hospital in Cape Town. A semi-structured interview which was audio-taped and transcribed verbatim was employed to collect data. Colaizzi's (1978) seven step inductive method was used to formulate naïve themes. Following participant feedback, three main themes emerged: care of the dead body, detachment and thanatophobia. Safeguarding the integrity and physical appearance of the dead body was the major finding and of the utmost priority for the participants in this study. Regardless of how the nurses felt about death, providing professional and quality care to the dead body and the family was seen as significantly important. The nurses, whilst performing post mortem care, experienced detachment from various relationships. This comprised of the nurse detaching him/herself professionally and emotionally from the dead patient, the family and him/herself from the death experience. This 'unspoken' experience of thanatophobia became apparent when the nurses were confronted by the reality of their own deaths. In a technological society, where answers to many questions can be pursued through science, understanding the experience of death, as opposed to dying, may be logically incomprehensible. Death remains one of the most traumatic events experienced by the patient and their family, and in some instances nurses themselves. The study has drawn attention to the nurses' experiences and in doing so; the emotional and educational needs have been

  11. MR arthrography: pharmacology, efficacy and safety in clinical trials

    International Nuclear Information System (INIS)

    Schulte-Altedorneburg, G.; Gebhard, M.; Wohlgemuth, W.A.; Fischer, W.; Zentner, J.; Bohndorf, K.; Wegener, R.; Balzer, T.

    2003-01-01

    A meta-analysis was carried out of clinical trials published between 1987 and 2001 in respect of the clinical pharmacology and safety as well as the diagnostic efficacy of gadolinium-DTPA (Gd-DTPA) for direct intra-articular injection before MRI examination.Design. Scientific papers (clinical, postmortem and experimental studies) and information from the manufacturer regarding intra-articular injection of Gd-DTPA that addressed questions of mode of action, optimal concentration and dose, elimination and safety were reviewed. Clinical studies were classified according to their study design. The sensitivity, specificity and accuracy of MR arthrography (MRA) were compared with a ''gold standard'' (arthroscopy, arthrotomy) and other radiological evidence for different joints.Results. Fifty-two clinical studies of the overall 112 studies addressed aspects of diagnostic efficacy of MRA in patients or in healthy volunteers. The shoulder was the most assessed joint (29 of 52 studies). Good (>80%) or even excellent (90-100%) sensitivity, specificity and accuracy were found for MRA in most indications, especially for the shoulder and knee joints and induced extension of rotator cuff lesions, labrum abnormalities and postoperative meniscal tears. Two millimoles per liter has proven to be the best concentration for intra-articular administration of Gd-DTPA. After passive complete diffusion from the joint within 6-24 h, complete and rapid renal elimination takes place after intra-articular injection. Local safety proved to be excellent after intra-articular administration of Gd-DTPA. Regarding systemic tolerance almost no side effects have been reported, but the same safety considerations apply for intra-articular administration of Gd-DTPA as for intravenous injection.Conclusions. The diagnostic efficacy of intra-articular MRA in most clinical conditions affecting major joints is greater than that of plain MRI. In some diagnostic problems MRA achieves almost the same

  12. Clinical Pharmacology of Furosemide in Neonates: A Review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2013-09-01

    Full Text Available Furosemide is the diuretic most used in newborn infants. It blocks the Na+-K+-2Cl− symporter in the thick ascending limb of the loop of Henle increasing urinary excretion of Na+ and Cl−. This article aimed to review the published data on the clinical pharmacology of furosemide in neonates to provide a critical, comprehensive, authoritative and, updated survey on the metabolism, pharmacokinetics, pharmacodynamics and side-effects of furosemide in neonates. The bibliographic search was performed using PubMed and EMBASE databases as search engines; January 2013 was the cutoff point. Furosemide half-life (t1/2 is 6 to 20-fold longer, clearance (Cl is 1.2 to 14-fold smaller and volume of distribution (Vd is 1.3 to 6-fold larger than the adult values. t1/2 shortens and Cl increases as the neonatal maturation proceeds. Continuous intravenous infusion of furosemide yields more controlled diuresis than the intermittent intravenous infusion. Furosemide may be administered by inhalation to infants with chronic lung disease to improve pulmonary mechanics. Furosemide stimulates prostaglandin E2 synthesis, a potent dilator of the patent ductus arteriosus, and the administration of furosemide to any preterm infants should be carefully weighed against the risk of precipitation of a symptomatic patent ductus arteriosus. Infants with low birthweight treated with chronic furosemide are at risk for the development of intra-renal calcifications.

  13. Clinical Pharmacology of Fentanyl in Preterm Infants. A Review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2015-06-01

    Full Text Available Fentanyl is a synthetic opioid that is very important in anesthetic practice because of its relatively short time to peak analgesic effect and the rapid termination of action after small bolus doses. The objective of this survey is to review the clinical pharmacology of fentanyl in preterm infants. The bibliographic search was performed using PubMed and EMBASE databases as search engines. In addition, the books Neofax: A manual of drugs used in neonatal care and Neonatal formulary were consulted. Fentanyl is N-dealkylated by CYP3A4 into the inactive norfentanyl. Fentanyl may be administered as bolus doses or as a continuous infusion. In neonates, there is a remarkable interindividual variability in the kinetic parameters. In neonates, fentanyl half-life ranges from 317 minutes to 1266 minutes and in adults it is 222 minutes. Respiratory depression occurs when fentanyl doses are >5 μg/kg. Chest wall rigidity may occur in neonates and occasionally is associated with laryngospasm. Tolerance to fentanyl may develop after prolonged use of this drug. Significant withdrawal symptoms have been reported in infants treated with continuous infusion for 5 days or longer. Fentanyl is an extremely potent analgesic and is the opioid analgesic most frequently used in the neonatal intensive care unit.

  14. 21 CFR 320.28 - Correlation of bioavailability with an acute pharmacological effect or clinical evidence.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Correlation of bioavailability with an acute pharmacological effect or clinical evidence. 320.28 Section 320.28 Food and Drugs FOOD AND DRUG ADMINISTRATION... Correlation of bioavailability with an acute pharmacological effect or clinical evidence. Correlation of in...

  15. 75 FR 10488 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-03-08

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  16. 76 FR 3912 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2011-01-21

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  17. 78 FR 42966 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-07-18

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  18. 77 FR 41790 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-07-16

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  19. 77 FR 42746 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-07-20

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  20. 78 FR 58314 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2013-09-23

    ...] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General... session, the Office of Pharmaceutical Science and the Office of Compliance will discuss with the committee...

  1. 77 FR 1696 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2012-01-11

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  2. 75 FR 8368 - Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting

    Science.gov (United States)

    2010-02-24

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0067] Advisory Committee for Pharmaceutical Science and Clinical Pharmacology; Notice of Meeting AGENCY: Food and... of Committee: Advisory Committee for Pharmaceutical Science and Clinical Pharmacology. General...

  3. Post-stroke Movement Disorders: Clinical Manifestations and Pharmacological Management.

    Science.gov (United States)

    Siniscalchi, Antonio; Gallelli, Luca; Labate, Angelo; Malferrari, Giovanni; Palleria, Caterina; Sarro, Giovambattista De

    2012-09-01

    Involuntary abnormal movements have been reported after ischaemic and haemorrhagic stroke. Post stroke movement disorders can appear as acute or delayed sequel. At the moment, for many of these disorders the knowledge of pharmacological treatment is still inadequate. Dopaminergic and GABAergic systems may be mainly involved in post-stroke movement disorders. This article provides a review on drugs commonly used in post-stroke movement disorders, given that some post-stroke movement disorders have shown a partial benefit with pharmacological approach.

  4. Understanding Early Post-Mortem Biochemical Processes Underlying Meat Color and pH Decline in the Longissimus thoracis Muscle of Young Blond d'Aquitaine Bulls Using Protein Biomarkers.

    Science.gov (United States)

    Gagaoua, Mohammed; Terlouw, E M Claudia; Micol, Didier; Boudjellal, Abdelghani; Hocquette, Jean-François; Picard, Brigitte

    2015-08-05

    Many studies on color biochemistry and protein biomarkers were undertaken in post-mortem beef muscles after ≥24 hours. The present study was conducted on Longissimus thoracis muscles of 21 Blond d'Aquitaine young bulls to evaluate the relationships between protein biomarkers present during the early post-mortem and known to be related to tenderness and pH decline and color development. pH values at 45 min, 3 h, and 30 h post-mortem were correlated with three, seven, and six biomarkers, respectively. L*a*b* color coordinates 24 h post-mortem were correlated with nine, five, and eight protein biomarkers, respectively. Regression models included Hsp proteins and explained between 47 and 59% of the variability between individuals in pH and between 47 and 65% of the variability in L*a*b* color coordinates. Proteins correlated with pH and/or color coordinates were involved in apoptosis or had antioxidative or chaperone activities. The main results include the negative correlations between pH45 min, pH3 h, and pHu and Prdx6, which may be explained by the antioxidative and phospholipase activities of this biomarker. Similarly, inducible Hsp70-1A/B and μ-calpain were correlated with L*a*b* coordinates, due to the protective action of Hsp70-1A/B on the proteolytic activities of μ-calpain on structural proteins. Correlations existed further between MDH1, ENO3, and LDH-B and pH decline and color stability probably due to the involvement of these enzymes in the glycolytic pathway and, thus, the energy status of the cell. The present results show that research using protein indicators may increase the understanding of early post-mortem biological mechanisms involved in pH and beef color development.

  5. Mephedrone (4-methylmethcathinone; 'meow meow'): chemical, pharmacological and clinical issues.

    Science.gov (United States)

    Schifano, Fabrizio; Albanese, Antonio; Fergus, Suzanne; Stair, Jackie L; Deluca, Paolo; Corazza, Ornella; Davey, Zoe; Corkery, John; Siemann, Holger; Scherbaum, Norbert; Farre', Magi'; Torrens, Marta; Demetrovics, Zsolt; Ghodse, A Hamid

    2011-04-01

    Recently, those substances deriving from the active ingredient of the Khat plant, cathinone, have been rising in popularity. Indeed, 4-methylmethcathinone (mephedrone; 'meow meow' and others) has been seen by some as a cheaper alternative to other classified recreational drugs. We aimed here at providing a state-of-the-art review on mephedrone history and prevalence of misuse, chemistry, pharmacology, legal status, product market appearance, clinical/management and related fatalities. Because of the limited evidence, some of the information here presented has been obtained from user reports/drug user-orientated web sites. The most common routes for mephedrone recreational use include insufflation and oral ingestion. It elicits stimulant and empathogenic effects similar to amphetamine, methylamphetamine, cocaine and MDMA. Due to its sympathomimetic actions, mephedrone may be associated with a number of both physical and psychopathological side effects. Recent preliminary analysis of recent UK data carried out in 48 related cases have provided positive results for the presence of mephedrone at postmortem. Within the UK, diffusion of mephedrone may have been associated with an unprecedented combination of a particularly aggressive online marketing policy and a decreasing availability/purity of both ecstasy and cocaine. Mephedrone has been recently classified in both the UK and in a number of other countries as a measure to control its availability. Following this, a few other research psychoactives have recently entered the online market as yet unregulated substances that may substitute for mephedrone. Only international collaborative efforts may be able to tackle the phenomenon of the regular offer of novel psychoactive drugs.

  6. Influence of operational condition on lithium plating for commercial lithium-ion batteries – Electrochemical experiments and post-mortem-analysis

    International Nuclear Information System (INIS)

    Ecker, Madeleine; Shafiei Sabet, Pouyan; Sauer, Dirk Uwe

    2017-01-01

    Highlights: •Investigation of lithium plating to support reliable system integration. •Influence of operational conditions at low temperature on lithium plating. •Comparison of different lithium-ion battery technologies. •Large differences in low-temperature behaviour for different technologies. •Post-mortem analysis reveals inhomogeneous deposition of metallic lithium. -- Abstract: The lifetime and safety of lithium-ion batteries are key requirements for successful market introduction of electro mobility. Especially charging at low temperature and fast charging, known to provoke lithium plating, is an important issue for automotive engineers. Lithium plating, leading both to ageing as well as safety risks, is known to play a crucial role in system design of the application. To gain knowledge of different influence factors on lithium plating, low-temperature ageing tests are performed in this work. Commercial lithium-ion batteries of various types are tested under various operational conditions such as temperature, current, state of charge, charging strategy as well as state of health. To analyse the ageing behaviour, capacity fade and resistance increase are tracked over lifetime. The results of this large experimental survey on lithium plating provide support for the design of operation strategies for the implementation in battery management systems. To further investigate the underlying degradation mechanisms, differential voltage curves and impedance spectra are analysed and a post-mortem analysis of anode degradation is performed for a selected technology. The results confirm the deposition of metallic lithium or lithium compounds in the porous structure and suggest a strongly inhomogeneous deposition over the electrode thickness with a dense deposition layer close to the separator for the considered cell. It is shown that this inhomogeneous deposition can even lead to loss of active material. The plurality of the investigated technologies

  7. Axial osteitis of the proximal sesamoid bones and desmitis of the intersesamoidean ligament in the hindlimb of Friesian horses: review of 12 cases (2002-2012) and post-mortem analysis of the bone-ligament interface.

    Science.gov (United States)

    Brommer, Harold; Voermans, Margreet; Veraa, Stefanie; van den Belt, Antoon J M; van der Toorn, Annette; Ploeg, Margreet; Gröne, Andrea; Back, Willem

    2014-11-19

    Axial osteitis of the proximal sesamoid bones and desmitis of the intersesamoidean ligament has been described in Friesian horses as well as in other breeds. The objectives of this study were to review the outcome of clinical cases of this disease in Friesian horses and analyse the pathology of the bone-ligament interface. Case records of Friesian horses diagnosed with axial osteitis of the proximal sesamoid bones and desmitis of the intersesamoidean ligament in the period 2002-2012 were retrospectively evaluated. Post-mortem examination was performed on horses that were euthanized (n = 3) and included macroscopic necropsy (n = 3), high-field (9.4 Tesla) magnetic resonance imaging (n = 1) and histopathology (n = 2). Twelve horses were included, aged 6.8 ± 2.7 years. The hindlimb was involved in all cases. Lameness was acute in onset and severe, with a mean duration of 1.9 ± 1.0 months. Three horses were euthanized after diagnosis; 9 horses underwent treatment. Two horses (22%) became sound for light riding purposes, 2 horses (22%) became pasture sound (comfortable at pasture, but not suitable for riding), 5 horses (56%) remained lame. In addition to bone resorption at the proximo-axial margin of the proximal sesamoid bones, magnetic resonance imaging and histopathology showed osteoporosis of the peripheral compact bone and spongious bone of the proximal sesamoid bones and chronic inflammation of the intersesamoidean ligament. Axial osteitis of the proximal sesamoid bones and desmitis of the intersesamoidean ligament in the hindlimb of Friesian horses carries a poor prognosis. Pathological characterization (inflammation, proximo-axial bone resorption and remodelling of the peripheral compact bone and spongious bone of the proximal sesamoid bones) may help in unravelling the aetiology of this disease.

  8. An Endocrine Pharmacology Course for the Clinically-Oriented Pharmacy Curriculum

    Science.gov (United States)

    Rahwan, Ralf G.

    1976-01-01

    In view of trends in clinical pharmacy education, the role of the traditional basic sciences has to be reassessed. An endocrine pharmacology course comprised of 49 clock-hours and open for professional undergraduate and graduate credit is described that blends basic and applied pharmacology. (LBH)

  9. A review of the pharmacology and clinical efficacy of brivaracetam

    Directory of Open Access Journals (Sweden)

    Klein P

    2018-01-01

    Full Text Available Pavel Klein,1 Anyzeila Diaz,2 Teresa Gasalla,3 John Whitesides4 1Mid-Atlantic Epilepsy and Sleep Center, Bethesda, MD, USA; 2Neurology Patient Value Unit, UCB Pharma, Smyrna, GA, USA; 3Neurology Patient Value Unit, UCB Pharma, Monheim am Rhein, Germany; 4Asset Development, UCB Pharma, Raleigh, NC, USA Abstract: Brivaracetam (BRV; Briviact is a new antiepileptic drug (AED approved for adjunctive treatment of focal (partial-onset seizures in adults. BRV is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A with 15- to 30-fold higher affinity than levetiracetam, the first AED acting on SV2A. It has high lipid solubility and rapid brain penetration, with engagement of the target molecule, SV2A, within minutes of administration. BRV has potent broad-spectrum antiepileptic activity in animal models. Phase I studies indicated BRV was well tolerated and showed a favorable pharmacokinetic profile over a wide dose range following single (10–1,000 mg and multiple (200–800 mg/day oral dosing. Three pivotal Phase III studies have demonstrated promising efficacy and a good safety and tolerability profile across doses of 50–200 mg/day in the adjunctive treatment of refractory focal seizures. Long-term data indicate that the response to BRV is sustained, with good tolerability and retention rate. BRV is highly effective in patients experiencing secondarily generalized tonic–clonic seizures. Safety data to date suggest a favorable psychiatric adverse effect profile in controlled studies, although limited postmarketing data are available. BRV is easy to use, with no titration and little drug–drug interaction. It can be initiated at target dose with no titration. Efficacy is seen on day 1 of oral use in a significant percentage of patients. Intravenous administration in a 2-minute bolus and 15-minute infusion is well tolerated. Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV. Keywords: brivaracetam, efficacy

  10. Simple spectrophotometric methods for determination of fluoxetine and clomipramine hydrochlorides in dosage forms and in some post-mortem biological fluids samples

    Directory of Open Access Journals (Sweden)

    Emam A. Ali

    2016-12-01

    Full Text Available Sensitive, simple and rapid spectrophotometric methods for micro determination of fluoxetine hydrochloride (FLU and clomipramine hydrochloride (CLO. The methods are based on the reaction between the examined drugs and acid dyes, namely; bromocresol green (BCG, phenol red (PhR and metanil yellow (MY producing yellow ion-pair complexes followed by their extraction with methylene chloride and measured at 412, 407 and 409 nm for FLU with BCG, PhR and MY, respectively; whereas for CLO at 409, 406 and 407 nm, respectively. All variables that affect the performance of the proposed methods were carefully studied and optimized. Beer’s law was obeyed in the concentration ranges 0.86–24.32 μg/mL, 8.64–41.30 μg/mL, 0.86–34.76 μg/mL for FLU and 1.75–24.55 μg/mL, 7.0–50 μg/mL, 1.65–34.78 μg/mL for CLO using BCG, PhR and MY respectively. The methods were validated in terms of accuracy and precision. The proposed methods were successfully applied to the determination of fluoxetine hydrochloride and clomipramine hydrochloride in pure samples, pharmaceutical formulations, spiked post-mortem urine and blood samples.

  11. A morphometric study of measurements of heart in adults and its relation with age and height of the individual: A post-mortem study

    Directory of Open Access Journals (Sweden)

    Chandni Gupta

    2014-01-01

    Full Text Available Objective: Reconstructive and replacement operations of diseased cardiac valves are commonly practiced these days. It may be noted that the choice of proper reconstructive intervention and prosthetic replacement might require the normal morphometric measurements of heart in relation with general body parameters, like age and height. So, this study was undertaken to measure various measurements of heart and its relation with age and height of the individual. Materials and Methods: Sixty five normal post-mortem hearts of adults were taken from the mortuary of Department of Forensic Medicine. Age of the individual was noted. Length of the deceased was measured with a measuring tape from the level of vertex to the outer border of heel. Length (from apex to base, breadth (at broadest diameter and thickness of the heart were measured with slide callipers. Weight was measured with weighing machine. Results: The mean length, breadth, thickness of heart in males and females are 11.25, 8.78, 3.97 cm and 10.60, 8.31, 3.63 cm. The mean weight of heart in males and females was 323 and 276 gms. There was significant correlation with weight of individual and weight of heart in males. There was significant correlation with age of individual and length of heart in females. Conclusion: This study will be helpful for cardiothoracic surgeons while doing surgery on hearts.

  12. High resolution post-mortem MRI of non-fixed in situ foetal brain in the second trimester of gestation. Normal foetal brain development

    Energy Technology Data Exchange (ETDEWEB)

    Scola, Elisa; Palumbo, Giovanni; Avignone, Sabrina; Cinnante, Claudia Maria [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan (Italy); Conte, Giorgio [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan (Italy); Universita degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan (Italy); Boito, Simona; Persico, Nicola [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Department of Obstetrics and Gynaecology ' L. Mangiagalli' , Milan (Italy); Rizzuti, Tommaso [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Pathology Unit, Milan (Italy); Triulzi, Fabio [Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Neuroradiology Unit, Milan (Italy); Universita degli Studi di Milano, Department of Pathophysiology and Transplantation, Milan (Italy)

    2018-01-15

    To describe normal foetal brain development with high resolution post-mortem MRI (PMMRI) of non-fixed foetal brains. We retrospectively collected PMMRIs of foetuses without intracranial abnormalities and chromosomal aberrations studied after a termination of pregnancy due to extracranial abnormalities or after a spontaneous intrauterine death. PMMRIs were performed on a 3-T scanner without any fixation and without removing the brain from the skull. All PMMRIs were evaluated in consensus by two neuroradiologists. Our analysis included ten PMMRIs (median gestational age (GA): 21 weeks; range: 17-28 weeks). At 19 and 20 weeks of GA, the corticospinal tracts are recognisable in the medulla oblongata, becoming less visible from 21 weeks. Prior to 20 weeks the posterior limb of the internal capsule (PLIC) is more hypointense than surrounding deep grey nuclei; starting from 21 weeks the PLIC becomes isointense, and is hyperintense at 28 weeks. From 19-22 weeks, the cerebral hemispheres show transient layers: marginal zone, cortical plate, subplate, and intermediate, subventricular and germinal zones. PMMRI of non-fixed in situ foetal brains preserves the natural tissue contrast and skull integrity. We assessed foetal brain development in a small cohort of foetuses, focusing on 19-22 weeks of gestation. (orig.)

  13. Entomología forense: el ciclo de vida de la mosca verde Phaenicia eximia (Wiedemann (Diptera: Calliphoridae, como herramienta para estimar el intervalo post-mortem

    Directory of Open Access Journals (Sweden)

    Enio B. Cano

    2017-03-01

    Full Text Available Se estudió el ciclo de vida de la mosca verde Phaenicia eximia (Wiedemann en condiciones controladas de laboratorio a 26 o C, con una humedad relativa de 75% y un período de iluminación de 12 h de luz y 12 h de oscuridad. El tiempo promedio de desarrollo estimado desde la oviposición hasta la salida de los adultos fue de 306 h (una media de casi 13 días. Bajo estas condiciones de temperatura y humedad, los huevos duran cerca de 19 h (0.8 días, las larvas duran unas 170 h (7.1 días y las pupas unas 116 h (4.8 días. En los meses secos y fríos de noviembre y diciembre en condiciones naturales, el ciclo de vida empírico fue de 25 días, implicando que las bajas temperaturas ralentizan el crecimiento y las altas lo aceleran. Se discute acerca de la importancia del ciclo de vida en la estimación del intervalo post-mortem en casos de muertes violentas en Guatemala.

  14. Is survival improved by the use of NIV and PEG in amyotrophic lateral sclerosis (ALS)? A post-mortem study of 80 ALS patients.

    Science.gov (United States)

    Burkhardt, Christian; Neuwirth, Christoph; Sommacal, Andreas; Andersen, Peter M; Weber, Markus

    2017-01-01

    Non-invasive ventilation (NIV) and percutaneous gastrostomy (PEG) are guideline-recommended interventions for symptom management in amyotrophic lateral sclerosis (ALS). Their effect on survival is controversial and the impact on causes of death is unknown. To investigate the effect of NIV and PEG on survival and causes of death in ALS patients. Eighty deceased ALS patients underwent a complete post mortem analysis for causes of death between 2003 and 2015. Forty-two of these patients consented for genetic testing. Effects of NIV and PEG on survival and causes of death were analyzed in a multivariable Cox proportional hazard regression. Six patients, who requested assisted suicide causing drug-induced hypoxia, were excluded from final analysis. Respiratory failure was the main cause of death in 72 out of 74 patients. Fifteen out of 74 died of aspiration pneumonia 23/74 of bronchopneumonia and 8/74 of a combination of aspiration pneumonia and bronchopneumonia. Twenty died of hypoxia without concomitant infection, and six patients had pulmonary embolism alone or in combination with pneumonia. NIV (p = 0.01) and PEG (pNIV bronchopneumonia was significantly more frequent (p NIV patients. This effect was even more pronounced in limb onset patients (pNIV and PEG prolongs survival in ALS. This study supports current AAN and EFNS guidelines which recommend NIV and PEG as a treatment option in ALS. The risk of bronchopneumonia as cause of death may be increased by NIV.

  15. Metabolomic Profiling of Post-Mortem Brain Reveals Changes in Amino Acid and Glucose Metabolism in Mental Illness Compared with Controls

    Directory of Open Access Journals (Sweden)

    Rong Zhang

    2016-01-01

    Full Text Available Metabolomic profiling was carried out on 53 post-mortem brain samples from subjects diagnosed with schizophrenia, depression, bipolar disorder (SDB, diabetes, and controls. Chromatography on a ZICpHILIC column was used with detection by Orbitrap mass spectrometry. Data extraction was carried out with m/z Mine 2.14 with metabolite searching against an in-house database. There was no clear discrimination between the controls and the SDB samples on the basis of a principal components analysis (PCA model of 755 identified or putatively identified metabolites. Orthogonal partial least square discriminant analysis (OPLSDA produced clear separation between 17 of the controls and 19 of the SDB samples (R2CUM 0.976, Q2 0.671, p-value of the cross-validated ANOVA score 0.0024. The most important metabolites producing discrimination were the lipophilic amino acids leucine/isoleucine, proline, methionine, phenylalanine, and tyrosine; the neurotransmitters GABA and NAAG and sugar metabolites sorbitol, gluconic acid, xylitol, ribitol, arabinotol, and erythritol. Eight samples from diabetic brains were analysed, six of which grouped with the SDB samples without compromising the model (R2 CUM 0.850, Q2 CUM 0.534, p-value for cross-validated ANOVA score 0.00087. There appears on the basis of this small sample set to be some commonality between metabolic perturbations resulting from diabetes and from SDB.

  16. The potential of non-invasive pre- and post-mortem carcass measurements to predict the contribution of carcass components to slaughter yield of guinea pigs.

    Science.gov (United States)

    Barba, Lida; Sánchez-Macías, Davinia; Barba, Iván; Rodríguez, Nibaldo

    2018-06-01

    Guinea pig meat consumption is increasing exponentially worldwide. The evaluation of the contribution of carcass components to carcass quality potentially can allow for the estimation of the value added to food animal origin and make research in guinea pigs more practicable. The aim of this study was to propose a methodology for modelling the contribution of different carcass components to the overall carcass quality of guinea pigs by using non-invasive pre- and post mortem carcass measurements. The selection of predictors was developed through correlation analysis and statistical significance; whereas the prediction models were based on Multiple Linear Regression. The prediction results showed higher accuracy in the prediction of carcass component contribution expressed in grams, compared to when expressed as a percentage of carcass quality components. The proposed prediction models can be useful for the guinea pig meat industry and research institutions by using non-invasive and time- and cost-efficient carcass component measuring techniques. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Comparative analysis of bones, mites, soil chemistry, nematodes and soil micro-eukaryotes from a suspected homicide to estimate the post-mortem interval.

    Science.gov (United States)

    Szelecz, Ildikó; Lösch, Sandra; Seppey, Christophe V W; Lara, Enrique; Singer, David; Sorge, Franziska; Tschui, Joelle; Perotti, M Alejandra; Mitchell, Edward A D

    2018-01-08

    Criminal investigations of suspected murder cases require estimating the post-mortem interval (PMI, or time after death) which is challenging for long PMIs. Here we present the case of human remains found in a Swiss forest. We have used a multidisciplinary approach involving the analysis of bones and soil samples collected beneath the remains of the head, upper and lower body and "control" samples taken a few meters away. We analysed soil chemical characteristics, mites and nematodes (by microscopy) and micro-eukaryotes (by Illumina high throughput sequencing). The PMI estimate on hair 14 C-data via bomb peak radiocarbon dating gave a time range of 1 to 3 years before the discovery of the remains. Cluster analyses for soil chemical constituents, nematodes, mites and micro-eukaryotes revealed two clusters 1) head and upper body and 2) lower body and controls. From mite evidence, we conclude that the body was probably brought to the site after death. However, chemical analyses, nematode community analyses and the analyses of micro-eukaryotes indicate that decomposition took place at least partly on site. This study illustrates the usefulness of combining several lines of evidence for the study of homicide cases to better calibrate PMI inference tools.

  18. High resolution post-mortem MRI of non-fixed in situ foetal brain in the second trimester of gestation. Normal foetal brain development

    International Nuclear Information System (INIS)

    Scola, Elisa; Palumbo, Giovanni; Avignone, Sabrina; Cinnante, Claudia Maria; Conte, Giorgio; Boito, Simona; Persico, Nicola; Rizzuti, Tommaso; Triulzi, Fabio

    2018-01-01

    To describe normal foetal brain development with high resolution post-mortem MRI (PMMRI) of non-fixed foetal brains. We retrospectively collected PMMRIs of foetuses without intracranial abnormalities and chromosomal aberrations studied after a termination of pregnancy due to extracranial abnormalities or after a spontaneous intrauterine death. PMMRIs were performed on a 3-T scanner without any fixation and without removing the brain from the skull. All PMMRIs were evaluated in consensus by two neuroradiologists. Our analysis included ten PMMRIs (median gestational age (GA): 21 weeks; range: 17-28 weeks). At 19 and 20 weeks of GA, the corticospinal tracts are recognisable in the medulla oblongata, becoming less visible from 21 weeks. Prior to 20 weeks the posterior limb of the internal capsule (PLIC) is more hypointense than surrounding deep grey nuclei; starting from 21 weeks the PLIC becomes isointense, and is hyperintense at 28 weeks. From 19-22 weeks, the cerebral hemispheres show transient layers: marginal zone, cortical plate, subplate, and intermediate, subventricular and germinal zones. PMMRI of non-fixed in situ foetal brains preserves the natural tissue contrast and skull integrity. We assessed foetal brain development in a small cohort of foetuses, focusing on 19-22 weeks of gestation. (orig.)

  19. Post-mortem analysis on LiFePO4|Graphite cells describing the evolution & composition of covering layer on anode and their impact on cell performance

    Science.gov (United States)

    Lewerenz, Meinert; Warnecke, Alexander; Sauer, Dirk Uwe

    2017-11-01

    During cyclic aging of lithium-ion batteries the formation of a μm-thick covering layer on top of the anode facing the separator is found on top of the anode. In this work several post-mortem analyses of cyclic aged cylindrical LFP|Graphite cells are evaluated to give a detailed characterization of the covering layer and to find possible causes for the evolution of such a layer. The analyses of the layer with different methods return that it consists to high percentage of plated active lithium, deposited Fe and products of a solid electrolyte interphase (SEI). The deposition is located mainly in the center of the cell symmetrical to the coating direction. The origin of these depositions is assumed in locally overcharged particles, Fe deposition or inhomogeneous distribution of capacity density. As a secondary effect the deposition on one side increases the thickness locally; thereafter a pressure-induced overcharging due to charge agglomeration of the back side of the anode occurs. Finally a compact and dense covering layer in a late state of aging leads to deactivation of the covered parts of the anode and cathode due to suppressed lithium-ion conductivity. This leads to increasing slope of capacity fade and increase of internal resistance.

  20. Toward Identification of the Sexual Killer: A Comparison of Sexual Killers Engaging in Post-Mortem Sexual Interference and Non-Homicide Sexual Aggressors.

    Science.gov (United States)

    Higgs, Tamsin; Carter, Adam J; Stefanska, Ewa B; Glorney, Emily

    2017-08-01

    Establishing a model of sexual assault reflecting psychosocial and behavioral characteristics of perpetrators of sexual killing and rape is necessary for development in risk assessment and intervention. Methodological variations in defining sexual killing have amalgamated serial and non-serial offenders and perpetrators with direct and indirect associations between killing and sexual arousal. This study defined sexual killing specifying that killing should be directly linked to sexual arousal, and sampled 48 sexual killers, operationalized to include only those engaging in post-mortem sexual interference, with one or two known female victims (non-serial), from prison service national (England and Wales) databases. These sexual killers were compared with 48 non-homicide, life or indeterminately sentenced sexual aggressors on psychological and crime scene characteristics. Contrary to previous research, fatal outcomes were associated with neither stranger victims nor weapon presence; sexual killing was characterized by severity of violence less so than non-fatal assault. Sexual killers more often reported problems with emotional loneliness, empathic concern, and sexual entitlement than the sexual aggressors. Theoretical and applied implications are discussed.

  1. Post-stroke Movement Disorders: Clinical Manifestations and Pharmacological Management

    OpenAIRE

    Siniscalchi, Antonio; Gallelli, Luca; Labate, Angelo; Malferrari, Giovanni; Palleria, Caterina; Sarro, Giovambattista De

    2012-01-01

    Involuntary abnormal movements have been reported after ischaemic and haemorrhagic stroke. Post stroke movement disorders can appear as acute or delayed sequel. At the moment, for many of these disorders the knowledge of pharmacological treatment is still inadequate. Dopaminergic and GABAergic systems may be mainly involved in post-stroke movement disorders. This article provides a review on drugs commonly used in post-stroke movement disorders, given that some post-stroke movement disorders ...

  2. Clinical Pharmacology of Kinase Inhibitors in Oncology : Personalized and Optimzed Dosing

    NARCIS (Netherlands)

    Verheijen, Remy B.

    2017-01-01

    Kinase inhibitors are an important category of molecularly targeted therapies used for cancer. Verheijen’s doctoral thesis describes several clinical pharmacological studies to optimize and personalize the treatment of cancer with kinase inhibitors, using pharmacokinetics, molecular imaging and

  3. Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications.

    Science.gov (United States)

    Derendorf, H; Meltzer, E O

    2008-10-01

    Intranasal corticosteroids (INSs) are effective treatments for allergic rhinitis, rhinosinusitis, and nasal polyposis. In recent years, increased understanding of corticosteroid and glucocorticoid receptor pharmacology has enabled the development of molecules designed specifically to achieve potent, localized activity with minimal risk of systemic exposure. Pharmacologic potency studies using affinity and other assessments have produced similar rank orders of potency, with the most potent being mometasone furoate, fluticasone propionate, and its modification, fluticasone furoate. The furoate and propionate ester side chains render these agents highly lipophilic, which may facilitate their absorption through nasal mucosa and uptake across phospholipid cell membranes. These compounds demonstrate negligible systemic absorption. Systemic absorption rates are higher among the older corticosteroids (flunisolide, beclomethasone dipropionate, triamcinolone acetonide, and budesonide), which have bioavailabilities in the range of 34-49%. Studies, including 1-year studies with mometasone furoate, fluticasone propionate, and budesonide that evaluated potential systemic effects of INSs in children have generally found no adverse effects on hypothalamic-pituitary-adrenal axis function or growth. Clinical data suggest no significant differences in efficacy between the INSs. Theoretically, newer agents with lower systemic availability may be preferable, and may come closer to the pharmacokinetic/pharmacologic criteria for the ideal therapeutic choice.

  4. Value of monoenergetic dual-energy CT (DECT) for artefact reduction from metallic orthopedic implants in post-mortem studies.

    Science.gov (United States)

    Filograna, Laura; Magarelli, Nicola; Leone, Antonio; Guggenberger, Roman; Winklhofer, Sebastian; Thali, Michael John; Bonomo, Lorenzo

    2015-09-01

    The aim of this ex vivo study was to assess the performance of monoenergetic dual-energy CT (DECT) reconstructions to reduce metal artefacts in bodies with orthopedic devices in comparison with standard single-energy CT (SECT) examinations in forensic imaging. Forensic and clinical impacts of this study are also discussed. Thirty metallic implants in 20 consecutive cadavers with metallic implants underwent both SECT and DECT with a clinically suitable scanning protocol. Extrapolated monoenergetic DECT images at 64, 69, 88, 105, 120, and 130 keV and individually adjusted monoenergy for optimized image quality (OPTkeV) were generated. Image quality of the seven monoenergetic images and of the corresponding SECT image was assessed qualitatively and quantitatively by visual rating and measurements of attenuation changes induced by streak artefact. Qualitative and quantitative analyses showed statistically significant differences between monoenergetic DECT extrapolated images and SECT, with improvements in diagnostic assessment in monoenergetic DECT at higher monoenergies. The mean value of OPTkeV was 137.6 ± 4.9 with a range of 130 to 148 keV. This study demonstrates that monoenergetic DECT images extrapolated at high energy levels significantly reduce metallic artefacts from orthopedic implants and improve image quality compared to SECT examination in forensic imaging.

  5. Value of monoenergetic dual-energy CT (DECT) for artefact reduction from metallic orthopedic implants in post-mortem studies

    International Nuclear Information System (INIS)

    Filograna, Laura; Magarelli, Nicola; Leone, Antonio; Bonomo, Lorenzo; Guggenberger, Roman; Winklhofer, Sebastian; Thali, Michael John

    2015-01-01

    The aim of this ex vivo study was to assess the performance of monoenergetic dual-energy CT (DECT) reconstructions to reduce metal artefacts in bodies with orthopedic devices in comparison with standard single-energy CT (SECT) examinations in forensic imaging. Forensic and clinical impacts of this study are also discussed. Thirty metallic implants in 20 consecutive cadavers with metallic implants underwent both SECT and DECT with a clinically suitable scanning protocol. Extrapolated monoenergetic DECT images at 64, 69, 88, 105, 120, and 130 keV and individually adjusted monoenergy for optimized image quality (OPTkeV) were generated. Image quality of the seven monoenergetic images and of the corresponding SECT image was assessed qualitatively and quantitatively by visual rating and measurements of attenuation changes induced by streak artefact. Qualitative and quantitative analyses showed statistically significant differences between monoenergetic DECT extrapolated images and SECT, with improvements in diagnostic assessment in monoenergetic DECT at higher monoenergies. The mean value of OPTkeV was 137.6 ± 4.9 with a range of 130 to 148 keV. This study demonstrates that monoenergetic DECT images extrapolated at high energy levels significantly reduce metallic artefacts from orthopedic implants and improve image quality compared to SECT examination in forensic imaging. (orig.)

  6. Value of monoenergetic dual-energy CT (DECT) for artefact reduction from metallic orthopedic implants in post-mortem studies

    Energy Technology Data Exchange (ETDEWEB)

    Filograna, Laura [University of Zurich, Department of Forensic Medicine and Imaging, Institute of Forensic Medicine, Zurich (Switzerland); Catholic University of Rome, School of Medicine, University Hospital ' ' A. Gemelli' ' , Department of Radiological Sciences, Rome (Italy); Magarelli, Nicola; Leone, Antonio; Bonomo, Lorenzo [Catholic University of Rome, School of Medicine, University Hospital ' ' A. Gemelli' ' , Department of Radiological Sciences, Rome (Italy); Guggenberger, Roman; Winklhofer, Sebastian [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Thali, Michael John [University of Zurich, Department of Forensic Medicine and Imaging, Institute of Forensic Medicine, Zurich (Switzerland)

    2015-09-15

    The aim of this ex vivo study was to assess the performance of monoenergetic dual-energy CT (DECT) reconstructions to reduce metal artefacts in bodies with orthopedic devices in comparison with standard single-energy CT (SECT) examinations in forensic imaging. Forensic and clinical impacts of this study are also discussed. Thirty metallic implants in 20 consecutive cadavers with metallic implants underwent both SECT and DECT with a clinically suitable scanning protocol. Extrapolated monoenergetic DECT images at 64, 69, 88, 105, 120, and 130 keV and individually adjusted monoenergy for optimized image quality (OPTkeV) were generated. Image quality of the seven monoenergetic images and of the corresponding SECT image was assessed qualitatively and quantitatively by visual rating and measurements of attenuation changes induced by streak artefact. Qualitative and quantitative analyses showed statistically significant differences between monoenergetic DECT extrapolated images and SECT, with improvements in diagnostic assessment in monoenergetic DECT at higher monoenergies. The mean value of OPTkeV was 137.6 ± 4.9 with a range of 130 to 148 keV. This study demonstrates that monoenergetic DECT images extrapolated at high energy levels significantly reduce metallic artefacts from orthopedic implants and improve image quality compared to SECT examination in forensic imaging. (orig.)

  7. Investigations into the analysis of the rate of decay of the compound action potentials recorded from the rat sciatic nerve after death: significance for the prediction of the post-mortem period.

    Science.gov (United States)

    Nokes, L D; Daniel, D; Flint, T; Barasi, S

    1991-01-01

    There have been a number of papers that have reported the investigations of electrical stimulation of muscle groups in order to determine the post-mortem period. To the authors knowledge, no techniques have been described that analyse the compound action potentials (CAP) of various nerve fibre groups after death. This paper reports the monitoring of both the amplitude and latency changes of the CAP recorded from a stimulated rat sciatic nerve after death. Initial results suggest that the method my be useful in determining the early post-mortem period within 1 or 2 h after death. It may also be of use in measuring nerve conduction delay in various pathological conditions that can affect the neural network; for example diabetes.

  8. Association of Protein Distribution and Gene Expression Revealed by PET and Post-Mortem Quantification in the Serotonergic System of the Human Brain.

    Science.gov (United States)

    Komorowski, A; James, G M; Philippe, C; Gryglewski, G; Bauer, A; Hienert, M; Spies, M; Kautzky, A; Vanicek, T; Hahn, A; Traub-Weidinger, T; Winkler, D; Wadsak, W; Mitterhauser, M; Hacker, M; Kasper, S; Lanzenberger, R

    2017-01-01

    Regional differences in posttranscriptional mechanisms may influence in vivo protein densities. The association of positron emission tomography (PET) imaging data from 112 healthy controls and gene expression values from the Allen Human Brain Atlas, based on post-mortem brains, was investigated for key serotonergic proteins. PET binding values and gene expression intensities were correlated for the main inhibitory (5-HT1A) and excitatory (5-HT2A) serotonin receptor, the serotonin transporter (SERT) as well as monoamine oxidase-A (MAO-A), using Spearman's correlation coefficients (rs) in a voxel-wise and region-wise analysis. Correlations indicated a strong linear relationship between gene and protein expression for both the 5-HT1A (voxel-wise rs = 0.71; region-wise rs = 0.93) and the 5-HT2A receptor (rs = 0.66; 0.75), but only a weak association for MAO-A (rs = 0.26; 0.66) and no clear correlation for SERT (rs = 0.17; 0.29). Additionally, region-wise correlations were performed using mRNA expression from the HBT, yielding comparable results (5-HT1Ars = 0.82; 5-HT2Ars = 0.88; MAO-A rs = 0.50; SERT rs = -0.01). The SERT and MAO-A appear to be regulated in a region-specific manner across the whole brain. In contrast, the serotonin-1A and -2A receptors are presumably targeted by common posttranscriptional processes similar in all brain areas suggesting the applicability of mRNA expression as surrogate parameter for density of these proteins. © The Author 2016. Published by Oxford University Press.

  9. Impacts of post-mortem ageing prior to freezing on technological and oxidative properties of coarse ground lamb sausage in a model system.

    Science.gov (United States)

    Choe, Juhui; Kim, Hyun-Wook; Farouk, Mustafa M; Brad Kim, Yuan H

    2017-07-01

    The objective of this study was to evaluate the effects of ageing time of lamb loins prior to freezing on technological characteristics and oxidation stability of coarse ground lamb loin sausage using in a model system. Lamb loins ( M. longissimus lumborum , n = 25) were aged at -1.5°C for 0, 1, 2, 3, and 8 wk and then frozen for the remaining days (a total of 30 wk). The aged/frozen/thawed lamb loins were ground, and model sausages were formulated with 75% aged/frozen/thawed lamb loin, 25% water, 1.5% sodium chloride (NaCl) and 0.3% sodium tripolyphosphate. The pH and thaw/purge loss of aged/frozen/thawed lamb loins were evaluated, and protein functionality (protein solubility and emulsifying capacity), water-holding capacity and textural properties of model sausages were determined. Cooked model sausages were vacuum-packaged in a plastic bag and displayed under continuous fluorescent natural white light (3°C±1°C). Colour and lipid oxidation of the cooked model sausages were evaluated on 0 and 21 d of display storage. Ageing prior to freezing had no impact on pH and purge/thaw loss of lamb loins and the colour of cooked sausages (p>0.05) made from the loins. Lamb loins aged for at least 3 wk prior to freezing numerically improved total and myofibrillar protein solubilities (p>0.05) and emulsion activity index (p = 0.009) of meat batter, but decreased cooking loss (p = 0.003) and lipid oxidation (p<0.05) of model sausages. This study suggests that post-mortem ageing of raw meat prior to freezing could improve water-holding capacity and lipid oxidative stability of sausage made from the meat.

  10. The impact of body mass index in gene expression of reelin pathway mediators in individuals with schizophrenia and mood disorders: A post-mortem study.

    Science.gov (United States)

    Brietzke, Elisa; Trevizol, Alisson P; Fries, Gabriel R; Subramaniapillai, Mehala; Kapczinski, Flavio; McIntyre, Roger S; Mansur, Rodrigo B

    2018-04-13

    The objective of this study was to compare the expression of genes involved in the reelin pathway, in the post-mortem brain of individuals with schizophrenia (SZ) and mood disorders (MD) with a healthy control (HC) group; and to investigate the role f body mass index (BMI) as a potential mediator. The "Gene Expression in Postmortem dlPFC and Hippocampus from Schizophrenia and Mood Disorders" study holds microarray data on individuals with SZ, MD and HCs (from whom 849 specimens are from the dlPFC and 579 from the hippocampus). mRNA data was obtained using HumanHT-12 v4 BeadChip arrays (Illumina). Multivariate analysis of covariance were used to investigate the main effects of group and relevant covariates on RELNm, NOTCH1, GRIN1m, GRIN3A, CAMK2Gm, CAMK2A, CAMK2Bm, CAMK2N2, GRIN2Bm, GRIN2A, CREBBPm, APOE, LDLR and DAB1 gene expression. In the dlPFC, individuals with SZ had higher expression, relative to HCs, of APOE. Individuals with MD had higher expression, relative to HCs, of CAMK2A, CAMK2N2, and GRIN2Bm. Moreover, individuals with MD had higher expression, relative to SZ patients, of CAMK2N2. There were significant group by BMI effects for expression of RELN, CAMK2A, CAMK2N2, and GRIN2A. In the hippocampus, individuals with MD had lower expression, relative to HCs, of APOE. The results of this study suggest that the expression of genes related to the reelin pathway could be different between individuals with SZ and MD and healthy controls, with a greater vulnerability associated with greater BMI. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Metabolomics of Neurotransmitters and Related Metabolites in Post-Mortem Tissue from the Dorsal and Ventral Striatum of Alcoholic Human Brain.

    Science.gov (United States)

    Kashem, Mohammed Abul; Ahmed, Selina; Sultana, Nilufa; Ahmed, Eakhlas U; Pickford, Russell; Rae, Caroline; Šerý, Omar; McGregor, Iain S; Balcar, Vladimir J

    2016-02-01

    We report on changes in neurotransmitter metabolome and protein expression in the striatum of humans exposed to heavy long-term consumption of alcohol. Extracts from post mortem striatal tissue (dorsal striatum; DS comprising caudate nucleus; CN and putamen; P and ventral striatum; VS constituted by nucleus accumbens; NAc) were analysed by high performance liquid chromatography coupled with tandem mass spectrometry. Proteomics was studied in CN by two-dimensional gel electrophoresis followed by mass-spectrometry. Proteomics identified 25 unique molecules expressed differently by the alcohol-affected tissue. Two were dopamine-related proteins and one a GABA-synthesizing enzyme GAD65. Two proteins that are related to apoptosis and/or neuronal loss (BiD and amyloid-β A4 precursor protein-binding family B member 3) were increased. There were no differences in the levels of dopamine (DA), 3,4-dihydrophenylacetic acid (DOPAC), serotonin (5HT), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (HIAA), histamine, L-glutamate (Glu), γ-aminobutyric acid (GABA), tyrosine (Tyr) and tryptophan (Tryp) between the DS (CN and P) and VS (NAc) in control brains. Choline (Ch) and acetylcholine (Ach) were higher and norepinephrine (NE) lower, in the VS. Alcoholic striata had lower levels of neurotransmitters except for Glu (30 % higher in the alcoholic ventral striatum). Ratios of DOPAC/DA and HIAA/5HT were higher in alcoholic striatum indicating an increase in the DA and 5HT turnover. Glutathione was significantly reduced in all three regions of alcohol-affected striatum. We conclude that neurotransmitter systems in both the DS (CN and P) and the VS (NAc) were significantly influenced by long-term heavy alcohol intake associated with alcoholism.

  12. The Effect of Upper Body Mass and Initial Knee Flexion on the Injury Outcome of Post Mortem Human Subject Pedestrian Isolated Legs.

    Science.gov (United States)

    Petit, Philippe; Trosseille, Xavier; Dufaure, Nicolas; Dubois, Denis; Potier, Pascal; Vallancien, Guy

    2014-11-01

    In the ECE 127 Regulation on pedestrian leg protection, as well as in the Euro NCAP test protocol, a legform impactor hits the vehicle at the speed of 40 kph. In these tests, the knee is fully extended and the leg is not coupled to the upper body. However, the typical configuration of a pedestrian impact differs since the knee is flexed during most of the gait cycle and the hip joint applies an unknown force to the femur. This study aimed at investigating the influence of the inertia of the upper body (modelled using an upper body mass fixed at the proximal end of the femur) and the initial knee flexion angle on the lower limb injury outcome. In total, 18 tests were conducted on 18 legs from 9 Post Mortem Human Subjects (PMHS). The principle of these tests was to impact the leg at 40 kph using a sled equipped with 3 crushing steel tubes, the stiffness of which were representative of the front face of a European sedan (bonnet leading edge, bumper and spoiler). The mass of the equipped sled was 74.5 kg. The test matrix was designed to perform 4 tests in 4 configurations combining two upper body masses (either 0 or 3 kg) and two knee angles (0 or 20 degrees) at 40 kph (11 m/s) plus 2 tests at 9 m/s. Autopsies were performed on the lower limbs and an injury assessment was established. The findings of this study were first that the increase of the upper body mass resulted in more severe injuries, second that an initial flexion of the knee, corresponding to its natural position during the gait cycle, decreased the severity of the injuries, and third that based on the injury outcome, a test conducted with no upper body mass and the knee fully extended was as severe as a test conducted with a 3 kg upper body mass and an initial knee flexion of 20°.

  13. Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue

    Science.gov (United States)

    Love, Seth; Chalmers, Katy; Ince, Paul; Esiri, Margaret; Attems, Johannes; Jellinger, Kurt; Yamada, Masahito; McCarron, Mark; Minett, Thais; Matthews, Fiona; Greenberg, Steven; Mann, David; Kehoe, Patrick Gavin

    2014-01-01

    In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers. The scoring scheme and choice of staining methods were refined by open-forum discussion. The agreed protocol scored parenchymal and meningeal CAA on a 0-3 scale, capillary CAA as present/absent and vasculopathy on 0-2 scale, in the 4 cortical lobes that were scored separately. A further assessment involving three centres was then undertaken. Neuropathologists in three centres (Bristol, Oxford and Sheffield) independently scored sections from 75 cases (25 from each centre) and high inter-rater reliability was demonstrated. Stage two used the results of the three-centre assessment to validate the protocol by investigating previously described associations between APOE genotype (previously determined), and both CAA and vasculopathy. Association of capillary CAA with or without arteriolar CAA with APOE ε4 was confirmed. However APOE ε2 was also found to be a strong risk factor for the development of CAA, not only in AD but also in elderly non-demented controls. Further validation of this protocol and scoring scheme is encouraged, to aid its wider adoption to facilitate collaborative and replication studies of CAA. PMID:24754000

  14. Erratum: Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue.

    Science.gov (United States)

    Love, Seth; Chalmers, Katy; Ince, Paul; Esiri, Margaret; Attems, Johannes; Kalaria, Raj; Jellinger, Kurt; Yamada, Masahito; McCarron, Mark; Minett, Thais; Matthews, Fiona; Greenberg, Steven; Mann, David; Kehoe, Patrick Gavin

    2015-01-01

    In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers. The scoring scheme and choice of staining methods were refined by open-forum discussion. The agreed protocol scored parenchymal and meningeal CAA on a 0-3 scale, capillary CAA as present/absent and vasculopathy on 0-2 scale, in the 4 cortical lobes that were scored separately. A further assessment involving three centres was then undertaken. Neuropathologists in three centres (Bristol, Oxford and Sheffield) independently scored sections from 75 cases (25 from each centre) and high inter-rater reliability was demonstrated. Stage two used the results of the three-centre assessment to validate the protocol by investigating previously described associations between APOE genotype (previously determined), and both CAA and vasculopathy. Association of capillary CAA with or without arteriolar CAA with APOE ε4 was confirmed. However APOE ε2 was also found to be a strong risk factor for the development of CAA, not only in AD but also in elderly non-demented controls. Further validation of this protocol and scoring scheme is encouraged, to aid its wider adoption to facilitate collaborative and replication studies of CAA.[This corrects the article on p. 19 in vol. 3, PMID: 24754000.].

  15. Post-Mortem Evaluation of Pathological Lesions in European Bison (Bison Bonasus in the Białowieża Primeval Forest Between 2008 and 2013

    Directory of Open Access Journals (Sweden)

    K. Krzysiak Michał

    2014-10-01

    Full Text Available The study presents the analysis of the findings of 234 post-mortem examinations on free-ranging and captive European bison selectively culled or having fallen between 2008 and 2013 in Białowieża Primeval Forest. Pneumonia, emphysema, nephritis, bodily traumas, and intestinal lesions were observed in 106 (45.3%, 77 (32.9%, 82 (35.0%, 68 (29.1%, and 56 (23.9% animals respectively and were the most common pathological changes. Almost half of all males (66 out of 140; 47.1% tested showed some pathological changes of prepuce and penis, described as posthitis or balanoposthitis. Infection with liver fluke (Fasciola hepatica and lungworm (Dictyocaulus viviparus was observed macroscopically in 114 (48.7% and 80 (32.9% bison respectively. F. hepatica prevalence was associated with the emergence of other liver changes such as hepatitis and cirrhosis (P < 0.001. Similarly, the prevalence of D. viviparus coincided with pneumonia (P = 0.001, changes in the upper respiratory tract (P = 0.04, and emphysema (P < 0.001. Hepatitis, infection with F. hepatica, and pathological lesions in the male and female reproductive tracts were associated with the animals’ age. Mechanical injuries, caused by other bison or less commonly by traffic accidents, were the most common cause of death of bison below six months of age. Most pathological changes were significantly more frequent in the selectively culled animals in comparison with the ones having fallen, which confirms the desirability of elimination as a tool to improve the health and welfare of the bison population and limit the number of reservoirs of invasive and possibly infectious diseases.

  16. Impacts of post-mortem ageing prior to freezing on technological and oxidative properties of coarse ground lamb sausage in a model system

    Directory of Open Access Journals (Sweden)

    Juhui Choe

    2017-07-01

    Full Text Available Objective The objective of this study was to evaluate the effects of ageing time of lamb loins prior to freezing on technological characteristics and oxidation stability of coarse ground lamb loin sausage using in a model system. Methods Lamb loins (M. longissimus lumborum, n = 25 were aged at −1.5°C for 0, 1, 2, 3, and 8 wk and then frozen for the remaining days (a total of 30 wk. The aged/frozen/thawed lamb loins were ground, and model sausages were formulated with 75% aged/frozen/thawed lamb loin, 25% water, 1.5% sodium chloride (NaCl and 0.3% sodium tripolyphosphate. The pH and thaw/purge loss of aged/frozen/thawed lamb loins were evaluated, and protein functionality (protein solubility and emulsifying capacity, water-holding capacity and textural properties of model sausages were determined. Cooked model sausages were vacuum-packaged in a plastic bag and displayed under continuous fluorescent natural white light (3°C±1°C. Colour and lipid oxidation of the cooked model sausages were evaluated on 0 and 21 d of display storage. Results Ageing prior to freezing had no impact on pH and purge/thaw loss of lamb loins and the colour of cooked sausages (p>0.05 made from the loins. Lamb loins aged for at least 3 wk prior to freezing numerically improved total and myofibrillar protein solubilities (p>0.05 and emulsion activity index (p = 0.009 of meat batter, but decreased cooking loss (p = 0.003 and lipid oxidation (p<0.05 of model sausages. Conclusion This study suggests that post-mortem ageing of raw meat prior to freezing could improve water-holding capacity and lipid oxidative stability of sausage made from the meat.

  17. Dating Pupae of the Blow Fly Calliphora vicina Robineau–Desvoidy 1830 (Diptera: Calliphoridae for Post Mortem Interval—Estimation: Validation of Molecular Age Markers

    Directory of Open Access Journals (Sweden)

    Barbara K. Zajac

    2018-03-01

    Full Text Available Determining the age of juvenile blow flies is one of the key tasks of forensic entomology when providing evidence for the minimum post mortem interval. While the age determination of blow fly larvae is well established using morphological parameters, the current study focuses on molecular methods for estimating the age of blow flies during the metamorphosis in the pupal stage, which lasts about half the total juvenile development. It has already been demonstrated in several studies that the intraspecific variance in expression of so far used genes in blow flies is often too high to assign a certain expression level to a distinct age, leading to an inaccurate prediction. To overcome this problem, we previously identified new markers, which show a very sharp age dependent expression course during pupal development of the forensically-important blow fly Calliphora vicina Robineau–Desvoidy 1830 (Diptera: Calliphoridae by analyzing massive parallel sequencing (MPS generated transcriptome data. We initially designed and validated two quantitative polymerase chain reaction (qPCR assays for each of 15 defined pupal ages representing a daily progress during the total pupal development if grown at 17 °C. We also investigated whether the performance of these assays is affected by the ambient temperature, when rearing pupae of C. vicina at three different constant temperatures—namely 17 °C, 20 °C and 25 °C. A temperature dependency of the performance could not be observed, except for one marker. Hence, for each of the defined development landmarks, we can present gene expression profiles of one to two markers defining the mentioned progress in development.

  18. Is survival improved by the use of NIV and PEG in amyotrophic lateral sclerosis (ALS? A post-mortem study of 80 ALS patients.

    Directory of Open Access Journals (Sweden)

    Christian Burkhardt

    Full Text Available Non-invasive ventilation (NIV and percutaneous gastrostomy (PEG are guideline-recommended interventions for symptom management in amyotrophic lateral sclerosis (ALS. Their effect on survival is controversial and the impact on causes of death is unknown.To investigate the effect of NIV and PEG on survival and causes of death in ALS patients.Eighty deceased ALS patients underwent a complete post mortem analysis for causes of death between 2003 and 2015. Forty-two of these patients consented for genetic testing. Effects of NIV and PEG on survival and causes of death were analyzed in a multivariable Cox proportional hazard regression.Six patients, who requested assisted suicide causing drug-induced hypoxia, were excluded from final analysis. Respiratory failure was the main cause of death in 72 out of 74 patients. Fifteen out of 74 died of aspiration pneumonia 23/74 of bronchopneumonia and 8/74 of a combination of aspiration pneumonia and bronchopneumonia. Twenty died of hypoxia without concomitant infection, and six patients had pulmonary embolism alone or in combination with pneumonia. NIV (p = 0.01 and PEG (p<0.01 had a significant impact on survival. In patients using NIV bronchopneumonia was significantly more frequent (p <0.04 compared to non-NIV patients. This effect was even more pronounced in limb onset patients (p<0.002. Patients with C9orf72 hexanucleotide repeat expansions showed faster disease progression and shorter survival (p = 0.01.The use of NIV and PEG prolongs survival in ALS. This study supports current AAN and EFNS guidelines which recommend NIV and PEG as a treatment option in ALS. The risk of bronchopneumonia as cause of death may be increased by NIV.

  19. Trace elements distribution and post-mortem intake in human bones from Middle Age by total reflection X-ray fluorescence

    International Nuclear Information System (INIS)

    Carvalho, M.L.; Marques, A.F.; Lima, M.T.; Reus, U.

    2004-01-01

    The purpose of the present work is to investigate the suitability of TXRF technique to study the distribution of trace elements along human bones of the 13th century, to conclude about environmental conditions and dietary habits of old populations and to study the uptake of some elements from the surrounding soil. In this work, we used TXRF to quantify and to make profiles of the elements through long bones. Two femur bones, one from a man and another from a woman, buried in the same grave were cross-sectioned in four different points at a distance of 1 cm. Microsamples of each section were taken at a distance of 1 mm from each other. Quantitative analysis was performed for Ca, Mn, Fe, Cu, Zn, Sr, Ba and Pb. Very high concentrations of Mn and Fe were obtained in the whole analysed samples, reaching values higher than 2% in some samples of trabecular tissue, very much alike to the concentrations in the burial soil. A sharp decrease for both elements was observed in cortical tissue. Zn and Sr present steady concentration levels in both kinds of bone tissues. Pb and Cu show very low concentrations in the inner tissue of cortical bone. However, these concentrations increase in the regions in contact to trabecular tissue and external surface in contact with the soil, where high levels of both elements were found. We suggest that contamination from the surrounding soil exists for Mn and Fe in the whole bone tissue. Pb can be both from post-mortem and ante-mortem origin. Inner compact tissue might represent in vivo accumulation and trabecular one corresponds to uptake during burial. The steady levels of Sr and Zn together with soil concentration lower levels for these elements may allow us to conclude that they are originated from in vivo incorporation in the hydroxyapatite bone matrix

  20. The pharmacologic and clinical effects of medical cannabis.

    Science.gov (United States)

    Borgelt, Laura M; Franson, Kari L; Nussbaum, Abraham M; Wang, George S

    2013-02-01

    Cannabis, or marijuana, has been used for medicinal purposes for many years. Several types of cannabinoid medicines are available in the United States and Canada. Dronabinol (schedule III), nabilone (schedule II), and nabiximols (not U.S. Food and Drug Administration approved) are cannabis-derived pharmaceuticals. Medical cannabis or medical marijuana, a leafy plant cultivated for the production of its leaves and flowering tops, is a schedule I drug, but patients obtain it through cannabis dispensaries and statewide programs. The effect that cannabinoid compounds have on the cannabinoid receptors (CB(1) and CB(2) ) found in the brain can create varying pharmacologic responses based on formulation and patient characteristics. The cannabinoid Δ(9) -tetrahydrocannabinol has been determined to have the primary psychoactive effects; the effects of several other key cannabinoid compounds have yet to be fully elucidated. Dronabinol and nabilone are indicated for the treatment of nausea and vomiting associated with cancer chemotherapy and of anorexia associated with weight loss in patients with acquired immune deficiency syndrome. However, pain and muscle spasms are the most common reasons that medical cannabis is being recommended. Studies of medical cannabis show significant improvement in various types of pain and muscle spasticity. Reported adverse effects are typically not serious, with the most common being dizziness. Safety concerns regarding cannabis include the increased risk of developing schizophrenia with adolescent use, impairments in memory and cognition, accidental pediatric ingestions, and lack of safety packaging for medical cannabis formulations. This article will describe the pharmacology of cannabis, effects of various dosage formulations, therapeutics benefits and risks of cannabis for pain and muscle spasm, and safety concerns of medical cannabis use. © 2013 Pharmacotherapy Publications, Inc.

  1. Clinical pharmacology in leishmaniasis: treatment optimization of a neglected disease

    NARCIS (Netherlands)

    Dorlo, T.P.C.

    2013-01-01

    This thesis presents various novel applications of clinical pharmacokinetics and pharmacodynamics in the treatment of leishmaniasis, by which diverse clinically relevant issues, mainly related to the efficacy and safety of miltefosine, could be elucidated. Throughout this thesis, the added value of

  2. Development of a Clinical Pharmacology Graduate Program at the University of Kentucky.

    Science.gov (United States)

    Blouin, Robert A.; And Others

    1994-01-01

    The structure, components, and anticipated outcomes of a University of Kentucky doctoral program in pharmacology are described. The program is designed to develop pharmacy-trained specialists who are interested in rigorous, intensive clinical experience, state-of-the-art coursework, and integrated laboratory-based and clinical dissertation…

  3. Alterações bioquímicas post-mortem de matrinxã Brycon cephalus (Günther, 1869 procedente da piscicultura, mantido em gelo Post-mortem biochemical alterations in aquacultured matrinxã fish Brycon cephalus (Günther, 1869 when stored on ice

    Directory of Open Access Journals (Sweden)

    Gilvan Machado Batista

    2004-12-01

    Full Text Available No presente trabalho, foram estudadas as alterações bioquímicas post-mortem que ocorreram em matrinxã Brycon cephalus (Günther, 1869 procedente da piscicultura e mantido em gelo em Manaus - AM. Foi determinado o tempo de estocagem em gelo por meio das avaliações sensoriais físicas e gustativas, das análises de pH, Nitrogênio das Bases Voláteis Totais (N-BVT e bacteriológicas durante 29 dias. Foram determinados os índices de rigor-mortis, as concentrações de ATP e seus produtos de degradações e o valor K. De acordo com a composição química, o peixe foi classificado como "semi-gordo". Os peixes entraram em rigor-mortis aos 75 minutos após a morte por hipotermia, tendo permanecido durante 10 dias. As avaliações sensoriais (físicas e gustativas mostraram que os peixes apresentaram condição de consumo até 26 dias. As análises de ATP e de seus produtos de degradação mostraram que a referida espécie foi considerada formadora de inosina (HxR, nas condições de experimento. O valor K mostrou que os exemplares de matrinxãs permaneceram "muito frescos" até 16 dias de estocagem em gelo, concordante com a avaliação sensorial gustativa.Post-mortem biochemical alterations in aquacultured matrinxã fish Brycon cephalus (Günther, 1869 when stored on ice in Manaus-AM, were studied in this paper. The storage time on ice was determined through tasting and physical sensory evaluations, pH, total volatile bases nitrogen (TVB-N and bacteriological analyses during 29 days. Rigor-mortis index, ATP-related compounds and K value were also determined. Chemical composition demonstrated that fish was classified as "semi-fat". The specimens presented rigor-mortis 75 minutes after death caused by hypothermia and remained that way for 10 days. Shelf life time on ice was 26 days, according to sensory evaluations, pH, TVBN determinations and bacteriological analyses. ATP-related compounds pointed out that the referred species was considered to

  4. Comparison of whole-body post mortem 3D CT and autopsy evaluation in accidental blunt force traumatic death using the abbreviated injury scale classification.

    Science.gov (United States)

    Daly, Barry; Abboud, Samir; Ali, Zabiullah; Sliker, Clint; Fowler, David

    2013-02-10

    Although 3D CT imaging data are available on survivors of accidental blunt trauma, little similar data has been collected and classified on major injuries in victims of fatal injuries. This study compared the sensitivity of post mortem computed tomography (PMCT) with that of conventional autopsy for major trauma findings classified according to the trauma Abbreviated Injury Scale (AIS). Whole-body 3D PMCT imaging data and full autopsy findings were analyzed on 21 victims of accidental blunt force trauma death. All major injuries were classified on the AIS scale with ratings from 3 (serious) to 6 (unsurvivable). Agreement between sensitivity of autopsy and PMCT for major injuries was determined. A total of 195 major injuries were detected (mean per fatality, 9.3; range, 1-14). Skeletal injuries by AIS grade included 37 grade 3, 45 grade 4, 12 grade 5, and 2 grade 6 major findings. Soft tissue injuries included 10 grade 3, 68 grade 4, 16 grade 5, and 5 grade 6 major findings. Of these, PMCT detected 165 (88 skeletal, 77 soft tissue), and autopsy detected 127 (59 skeletal, 68 soft tissue). PMCT agreed with autopsy in 86% and 76% of skeletal and soft tissue injuries, respectively. PMCT detected an additional 37 skeletal and 31 soft tissue injuries that were not identified at autopsy. Autopsy detected 8 skeletal and 22 soft tissue injuries that were not detected by PMCT. PMCT was more sensitive for skeletal (P=0.05) and head and neck region injury (P=0.043) detection. PMCT showed a trend for greater sensitivity than autopsy, but this did not reach statistical significance (P=0.083). 3D PMCT detected significantly more skeletal injuries than autopsy and a similar number of soft tissue injuries to autopsy and promises to be a sensitive tool for detection and classification of skeletal injuries in fatal blunt force accidental trauma. Use of the AIS scale allows standardized categorization and quantification of injuries that contribute to death in such cases and allows more

  5. Regional correlations between [11C]PIB PET and post-mortem burden of amyloid-beta pathology in a diverse neuropathological cohort

    Directory of Open Access Journals (Sweden)

    Sang Won Seo

    2017-01-01

    Full Text Available Imaging-pathological correlation studies show that in vivo amyloid-β (Aβ positron emission tomography (PET strongly predicts the presence of significant Aβ pathology at autopsy. We sought to determine whether regional PiB-PET uptake would improve sensitivity for amyloid detection in comparison with global measures (experiment 1, and to estimate the relative contributions of different Aβ aggregates to in vivo PET signal (experiment 2. In experiment 1, 54 subjects with [11C] PiB-PET during life and postmortem neuropathologic examination (85.2% with dementia, interval from PET to autopsy 3.1 ± 1.9 years were included. We assessed Thal amyloid phase (N = 36 and CERAD score (N = 54 versus both global and regional PiB SUVRs. In experiment 2 (N = 42, PiB SUVR and post-mortem amyloid β burden was analyzed in five customized regions of interest matching regions sampled at autopsy. We assessed the relative contribution of neuritic plaques (NPs, diffuse plaques (DPs and cerebral amyloid angiopathy (CAA to regional PIB SUVR using multi-linear regression. In experiment 1, there were no differences in Area Under the Curve for amyloid phase ≥ A2 and CERAD score ≥ C2 between global and highest regional PiB SUVR (p = 0.186 and 0.230. In experiment 2, when NPs, DPs, and/or CAA were included in the same model, moderate to severe NPs were independently correlated with PiB SUVR in all regions except for the inferior temporal and calcarine ROI (β = 0.414–0.804, p < 0.05, whereas DPs were independently correlated with PiB SUVR in the angular gyrus ROI (β = 0.446, p = 0.010. CAA was also associated with PiB SUVR in the inferior temporal and calcarine ROI (β = 0.222–0.355, p < 0.05. In conclusion, global PiB-PET SUVR performed as well as regional values for amyloid detection in our cohort. The substrate-specific binding of PiB might differ among the brain specific regions.

  6. Paper-based microfluidic devices on the crime scene: A simple tool for rapid estimation of post-mortem interval using vitreous humour.

    Science.gov (United States)

    Garcia, Paulo T; Gabriel, Ellen F M; Pessôa, Gustavo S; Santos Júnior, Júlio C; Mollo Filho, Pedro C; Guidugli, Ruggero B F; Höehr, Nelci F; Arruda, Marco A Z; Coltro, Wendell K T

    2017-06-29

    This paper describes for the first time the use of paper-based analytical devices at crime scenes to estimate the post-mortem interval (PMI), based on the colorimetric determination of Fe 2+ in vitreous humour (VH) samples. Experimental parameters such as the paper substrate, the microzone diameter, the sample volume and the 1,10-phenanthroline (o-phen) concentration were optimised in order to ensure the best analytical performance. Grade 1 CHR paper, microzone with diameter of 5 mm, a sample volume of 4 μL and an o-phen concentration of 0.05 mol/L were chosen as the optimum experimental conditions. A good linear response was observed for a concentration range of Fe 2+ between 2 and 10 mg/L and the calculated values for the limit of detection (LOD) and limit of quantification (LOQ) were 0.3 and 0.9 mg/L, respectively. The specificity of the Fe 2+ colorimetric response was tested in the presence of the main interfering agents and no significant differences were found. After selecting the ideal experimental conditions, four HV samples were investigated on paper-based devices. The concentration levels of Fe 2+ achieved for samples #1, #2, #3 and #4 were 0.5 ± 0.1, 0.7 ± 0.1, 1.2 ± 0.1 and 15.1 ± 0.1 mg/L, respectively. These values are in good agreement with those calculated by ICP-MS. It important to note that the concentration levels measured using both techniques are proportional to the PMI. The limitation of the proposed analytical device is that it is restricted to a PMI greater than 1 day. The capability of providing an immediate answer about the PMI on the crime scene without any sophisticated instrumentation is a great achievement in modern instrumentation for forensic chemistry. The strategy proposed in this study could be helpful in many criminal investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Os conflitos do consentimento acerca da doação de órgãos post mortem no Brasil

    Directory of Open Access Journals (Sweden)

    MAYNARD, Lorena Oliveira Dantas

    2015-11-01

    Full Text Available Com o refinamento das técnicas de cirurgias e imunogenética pela medicina nas últimas décadas e com os avanços na farmacoterapia, o transplante de órgãos e tecidos tornou-se uma possibilidade real e uma alternativa essencial ao prolongamento e à qualidade da vida humana. Este estudo objetivou analisar o consentimento para remoção de órgãos e tecidos post mortem na legislação brasileira, na perspectiva da autorização da família. Adotou-se, para tanto, estratégia metodológica qualitativa através de revisão de literatura e revisão legislativa, que permitem um aprofundamento no universo dos significados, dos motivos, das aspirações, das crenças, dos valores e das atitudes em relação ao tema. Os resultados apontam que, na atual Lei de Transplantes, os direitos da personalidade e o princípio da autonomia da vontade são institutos pouco homenageados em função da predominância do monopólio da decisão familiar na hipótese de um confronto entre a vontade do doador e a vontade da família. Frente ao problema da escassez de órgãos no país, a solução mais consentânea com a justiça seria uma adequação entre os dispositivos de lei do Código Civil e a Lei de Transplantes. Oportuno partir do texto já existente do artigo 4º da Lei n. 9.434/1997, para incluir a manifestação da vontade do doador em vida, devidamente documentada. É igualmente importante a informação e a conscientização popular sobre a natureza humanitária da doação de órgãos como medidas direcionadas à discussão do princípio da solidariedade para uma política de doação de órgãos.

  8. Post-mortem analysis of suicide victims shows ABCB1 haplotype 1236T-2677T-3435T as a candidate predisposing factor behind adverse drug reactions in females.

    Science.gov (United States)

    Rahikainen, Anna-Liina; Palo, Jukka U; Haukka, Jari; Sajantila, Antti

    2018-04-01

    Genetic variation in efflux transporter, permeability glycoprotein (P-gp), has recently been associated with completed violent suicides and also violent suicide attempts. As depression is known to be a risk factor for suicide and many antidepressants are P-gp substrates, it has been speculated that inadequate antidepressant treatment response or adverse side effects could be involved. The aim of this study was to investigate whether there is an association between the P-gp coding ABCB1 gene and completed suicides in citalopram users. Also, the effect of sex and suicide method used (violent vs. non-violent) was evaluated. All cases included in the study population, 349 completed suicide victims and 284 controls, were shown to be positive for antidepressant citalopram in a post-mortem toxicological drug screen. ABCB1 1236C>T, 2677G>T/A and 3435C>T polymorphisms were determined by TaqMan genotyping assays. Haplotypes were constructed from genotype data using the PHASE software. The association between the manner of death and the ABCB1 haplotype was tested with logistic regression analysis. No statistically significant differences were observed in the ABCB1 allele or genotype frequencies between the suicide and control groups. However, the ABCB1 1236T-2677T-3435T haplotype was associated with completed suicides of female citalopram users (odds ratio: 2.23; 95% confidence interval: 1.22-4.07; P=0.009). After stratification by the method used for suicide, the association emerged in fatal intoxications (odds ratio: 2.51; 95% confidence interval: 1.29-4.87; P=0.007). In other groups, no statistically significant associations were observed. Our results suggest that female citalopram users with ABCB1 1236T-2677T-3435T are more vulnerable to adverse effects of the drugs as this haplotype was enriched in non-violent suicides of female citalopram users. Even though the biological mechanism behind this observation is unknown, the results provide another example of the importance

  9. In vivo quantitative imaging of point-like bioluminescent and fluorescent sources: Validation studies in phantoms and small animals post mortem

    Science.gov (United States)

    Comsa, Daria Craita

    2008-10-01

    source strength within 20 %. For sources 14mm deep, the inaccuracy in determining the relative source strength increased to 30 %. Measurements on small animals post mortem showed that the use of measured in situ optical properties to characterize heterogeneous tissue resulted in a superior estimation of the source strength and depth compared to when literature optical properties for organs or tissues were used. Moreover, it was found that regardless of the heterogeneity of the implant location or depth, our algorithm consistently showed an advantage over the simple assessment of the source strength based on the signal strength in the emission image. Our bioluminescence algorithm was generally able to predict the source strength within a factor of 2 of the true strength, but the performance varied with the implant location and depth. In fluorescence imaging a more complex technique is required, including knowledge of tissue optical properties at both the excitation and emission wavelengths. A theoretical study using simulated fluorescence data showed that, for example, for a source 5 mm deep in tissue, errors of up to 15 % in the optical properties would give rise to errors of +/-0.7 mm in the retrieved depth and the source strength would be over- or under-estimated by a factor ranging from 1.25 to 2. Fluorescent sources implanted in rats post mortem at the same depth were localized with an error just slightly higher than predicted theoretically: a root-mean-square value of 0.8 mm was obtained for all implants 5 mm deep. However, for this source depth, the source strength was assessed within a factor ranging from 1.3 to 4.2 from the value estimated in a controlled medium. Nonetheless, similarly to the bioluminescence study, the fluorescence quantification algorithm consistently showed an advantage over the simple assessment of the source strength based on the signal strength in the fluorescence image. Few studies have been reported in the literature that reconstruct known

  10. Clinical, molecular, and pharmacological aspects of FMR1 related disorders.

    Science.gov (United States)

    Pugin, A; Faundes, V; Santa María, L; Curotto, B; Aliaga, S; Salas, I; Soto, P; Bravo, P; Peña, M I; Alliende, M A

    2017-05-01

    Fragile X syndrome, the most common inherited cause of intellectual disability, is associated with a broad spectrum of disorders across different generations of a single family. This study reviews the clinical manifestations of fragile X-associated disorders as well as the spectrum of mutations of the fragile X mental retardation 1 gene (FMR1) and the neurobiology of the fragile X mental retardation protein (FMRP), and also provides an overview of the potential therapeutic targets and genetic counselling. This disorder is caused by expansion of the CGG repeat (>200 repeats) in the 5 prime untranslated region of FMR1, resulting in a deficit or absence of FMRP. FMRP is an RNA-binding protein that regulates the translation of several genes that are important in synaptic plasticity and dendritic maturation. It is believed that CGG repeat expansions in the premutation range (55 to 200 repeats) elicit an increase in mRNA levels of FMR1, which may cause neuronal toxicity. These changes manifest clinically as developmental problems such as autism and learning disabilities as well as neurodegenerative diseases including fragile X-associated tremor/ataxia syndrome (FXTAS). Advances in identifying the molecular basis of fragile X syndrome may help us understand the causes of neuropsychiatric disorders, and they will probably contribute to development of new and specific treatments. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Pharmacological basis and clinical evidence of dabigatran therapy

    Directory of Open Access Journals (Sweden)

    Redondo Santiago

    2011-12-01

    Full Text Available Abstract Dabigatran is an emerging oral anticoagulant which is a direct inhibitor of thrombin activity. It has been approved in the European Union and the United States of America for the prevention of thrombosis after major orthopedic surgery. It has also been approved by the American Food and Drug Administration and the European Medicines Agency for the prevention of stroke in chronic atrial fibrillation. Dabigatran provides a stable anticoagulation effect without any need to perform periodical laboratory controls. Of note, there is a growing amount of clinical evidence which shows its safety and efficacy. For these reasons, dabigatran may suppose a revolution in oral anticoagulation. However, two important limitations remain. First, it is contraindicated in patients with end-stage renal disease. Second, there is no evidence of the prevention of thrombosis in mechanical heart valves.

  12. Preliminary clinical pharmacological investigations of tylosin and tiamulin in chickens.

    Science.gov (United States)

    Ziv, G

    1980-10-15

    The minimal inhibitory concentrations (MIC) of tiamulin and tylosin for mycoplasma, Gram-positive, and Gram-negative micro-organisms isolated from chickens were determinated by the agar dilution method. Median MIC values for tiamulin against Mycoplasma gallisepticum (0.05 microgram/ml) and Mycoplasma synoviae (0.10 microgram/ml) were 2 to 4 times lower than the corresponding values for tylosin. Tiamulin was also slightly more effective in vitro in inhibiting Escherichia coli, Pasteurella multocida, and beta-haemolytic streptococci than was tylosin. Groups of chicken were offered tiamulin medicated drinking water at rates of 125 and 250 mg/litre for 48 hours. Average serum tiamulin concentrations were 0.38 and 0.78 microgram/ml, respectively. When tylosin tartrate was added to the drinking water at 500 and 700 mg/litre, average serum drug levels were 0.12 and 0.17 microgram/ml, respectively. Tiamulin was 45% bound in chicken serum, as against 30% serum protein binding for tylosin. Correlations were made between free (non protein bound) serum drug levels and the MIC values of the two drugs. Such comparisons suggest that when tiamulin is given in the drinking water at rates of 125 to 250 mg/litre, better antimycoplasmal activity is to be expected in vivo than by giving tylosin tartrate in the drinking water at 500 to 700 mg/litre. Based on these data, no clinical efficacy of these dose rates can be expected in flocks infected by gram-negative micro-organisms such as E. coli or P. multocida. The tylosin tartrate rate of 500 to 700 mg/litre, may be clinical ineffective the treatment of Staphylococcus aureus infections.

  13. Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications.

    Science.gov (United States)

    Wuttke, W; Jarry, H; Christoffel, V; Spengler, B; Seidlová-Wuttke, D

    2003-05-01

    Extracts of the fruits of chaste tree (Vitex agnus castus = AC) are widely used to treat premenstrual symptoms. Double-blind placebo-controlled studies indicate that one of the most common premenstrual symptoms, i.e. premenstrual mastodynia (mastalgia) is beneficially influenced by an AC extract. In addition, numerous less rigidly controlled studies indicate that AC extracts have also beneficial effects on other psychic and somatic symptoms of the PMS. Premenstrual mastodynia is most likely due to a latent hyperprolactinemia, i.e. patients release more than physiologic amounts of prolactin in response to stressful situations and during deep sleep phases which appear to stimulate the mammary gland. Premenstrually this unphysiological prolactin release is so high that the serum prolactin levels often approach heights which are misinterpreted as prolactinomas. Since AC extracts were shown to have beneficial effects on premenstrual mastodynia serum prolactin levels in such patients were also studied in one double-blind, placebo-controlled clinical study. Serum prolactin levels were indeed reduced in the patients treated with the extract. The search for the prolactin-suppressive principle(s) yielded a number of compounds with dopaminergic properties: they bound to recombinant DA2-receptor protein and suppressed prolactin release from cultivated lactotrophs as well as in animal experiments. The search for the chemical identity of the dopaminergic compounds resulted in isolation of a number of diterpenes of which some clerodadienols were most important for the prolactin-suppressive effects. They were almost identical in their prolactin-suppressive properties than dopamine itself. Hence, it is concluded that dopaminergic compounds present in Vitex agnus castus are clinically the important compounds which improve premenstrual mastodynia and possibly also other symptoms of the premenstrual syndrome.

  14. Genetic, clinical and pharmacological determinants of out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Blom, M T; van Hoeijen, D A; Bardai, A

    2014-01-01

    INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Recognising the complexity of the underlying causes of OHCA in the community, we aimed to establish the clinical, pharmacological, environmental and genetic factors and their interactions that may cause OHCA. ME......-reviewed journals and presented at relevant scientific symposia....

  15. Review of the pharmacology and clinical studies of micafungin

    Directory of Open Access Journals (Sweden)

    Alison M Bormann

    2009-12-01

    Full Text Available Alison M Bormann1, Vicki A Morrison21Division of Infectious Diseases, University of Minnesota, Minneapolis, MN, USA; 2Division of Hematology/Oncology and Infectious Disease, Minneapolis Veterans Affairs Medical Center, Minneapolis, MN, USAAbstract: Micafungin, like other members of the echinocandin class, has a unique mechanism of action that inhibits the synthesis of 1,3-β-D glucans in the fungal cell wall. It has been approved for treatment of esophageal candidiasis, invasive candidiasis including candidemia, and for prophylaxis of Candida infections in patients undergoing hematopoietic stem cell transplantation. Although efficacy and safety have also been demonstrated in pediatric populations, micafungin is approved for this indication in Europe and Japan, but not in the United States. It has demonstrated activity against Candida spp. including those that are azole-resistant as well as Aspergillus and a few other clinically important molds. It is administered intravenously as a once daily infusion and does not require dose adjustments for renal or moderate hepatic dysfunction. Its safety record, favorable tolerability profile, and few drug interactions make it an important agent for the treatment of invasive fungal infections.Keywords: micafungin, antifungal therapy, echinocandins, fungal infections, Candida, Aspergillus

  16. Clinical Pharmacology of Phenobarbital in Neonates: Effects, Metabolism and Pharmacokinetics.

    Science.gov (United States)

    Pacifici, Gian M

    2016-01-01

    Phenobarbital is an effective and safe anticonvulsant drug introduced in clinical use in 1904. Its mechanism of action is the synaptic inhibition through an action on GABAA. The loading dose of phenobarbital is 20 mg/kg intravenously and the maintenance dose is 3 to 4 mg/kg by mouth. The serum concentration of phenobarbital is up to 40 µg/ml. Nonresponders should receive additional doses of 5 to 10 mg/kg until seizures stop. Infants with refractory seizures may have a serum concentration of phenobarbital of 100 µg/ml. Phenobarbital is metabolized in the liver by CYP2C9 with minor metabolism by CYP2C19 and CYP2E1. A quarter of the dose of phenobarbital is excreted unchanged in the urine. In adults, the half-life of phenobarbital is 100 hours and in term and preterm infants is 103 and 141 hours, respectively. The half-life of phenobarbital decreases 4.6 hours per day and it is 67 hours in infants 4 week old.

  17. Estudio post-mortem de un hormigón refractario colocado en la línea de escorias de una cuchara de acería

    Directory of Open Access Journals (Sweden)

    de Aza, A. H.

    2003-12-01

    Full Text Available A high alumina concrete with synthetic spinel (MgAl2O4 addition, conformed as a brick, has been tested in the slag line of a secondary steel ladle. A post-mortem study allowed to establish the elements diffusion profile inside the refractory as well as its microstructural evolution. This study was carried out by means of X-ray diffraction, reflected optical light microscopy and scanning electron microscopy coupled with energy dispersive X-ray analysis. From the analysis of the obtained results, making use of the Al2O3-MgO-CaO-SiO2 quaternary system, it has been possible to establish the mechanism of corrosion, justifying, at the same time, the role that spinel and calcium hexaluminate (CaAl12O19 play. The spinel, that is the only stable solid phase in the slag - refractory interface, admits in its structure large amount of bivalent and trivalent elements (e.g. Mn2+, Fe2+, Fe3+, Cr3+.... Therefore, the slag becomes silica-rich and highly viscous, as CaAl12O19 is precipitated, decreasing the corrosion. The calcium hexaluminate grows from coarse and medium-sized grains of alumina to form a network of interlocked crystals that act as unions among the alumina grains. This microstructure together with that the CaAl12O19 also admits in solid solution large quantities of Fe2+ and Fe3+, provide a smaller, slower and more uniform wear of the refractory material.

    Se ha diseñado y preparado un hormigón de alta alúmina con espinela, el cual ha sido ensayado, en forma de piezas preconformadas, en la línea de escorias de una cuchara de acería secundaria. El estudio post-morten del material ha permitido establecer las reacciones químicas que tienen lugar durante el proceso de corrosión y determinar el mecanismo imperante durante este proceso haciendo uso del diagrama de equilibrio Al2O3-MgO-CaO-SiO2. Dicho estudio se ha llevado a cabo mediante difracción de rayos X, microscopía óptica de luz reflejada y microscopía electrónica de barrido con

  18. A review on Pharmacological and clinical aspects of Linum usitatissimum L.

    Science.gov (United States)

    Ansari, Ramin; Zarshenas, Mohammad Mehdi; Dadbakhsh, Amir Hossein

    2018-05-20

    Linum usitatissimum L., known as common Flax or linseed, from the family Linnaceae, has long been cultivated in different nations due to its applications in medicine and industry. The present study aims to collect nearly all available information about chemical constituents of Flax, as well as pharmacological properties and confirmed clinical usages of it. We searched through databases such as Scopus and PubMed for relevant literatures using the keywords: (Linum usitatissimum), (pharmacology) and (phytochemical) from the beginning to 13 Aug 2017. Nearly 60 relevant papers, relating to pharmacological and phytochemical constituent of L. usitatissimum were selected. According to our researches, various properties were attributed to L. usitatisimum including: antioxidant, immunomodulatory, anti-inflammatory, antimicrobial, Antiprotozoal, insecticidal, Analgesic, anti-hyperlipidemia, Anti-hyperglycemic, Anti-tumor, wound healing and Feticidal activities. There were also many reports to the disease preventive and healing properties of the flax. Diseases like: GI disorders, cardiovascular, urogenital, respiratory diseases and some neurological syndromes were mentioned to be treated by Flax. The application of Flax in drug formulations was also investigated. Despite so much animal studies that have been accomplished, there haven't been enough clinical trials done on pharmacological properties of L. usitatissimum. Therefore this study could be considered as a concise and up to date overview for further facile studies and clinical trials over the valuable plant, L. usitatissimum. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. [Note on the epistemology of clinical pharmacology: comparison with the approach of Karl Popper].

    Science.gov (United States)

    Boissel, J P

    1999-01-01

    Is clinical pharmacology a science or only an application of science? Karl Popper suggested a method to identify science and to sort it out from other logical activities such as metaphysics, whereby the falsification criterion he proposed can apply to the theory in such a way that the theory could be refuted. The clinical pharmacologist's approach requires the build-up of a therapeutic model on the basis of two other models: the physiopathologic and the pharmacological. The three-model construct is a theory. Is it scientific in the Popperian sense? From the therapeutic model, one can predict the efficacy of a drug, and the corresponding statement is tested by a clinical trial. Whatever the original statement, it is modified into a refutable one because of the use of the statistical approach in clinical trials. Furthermore, the predicate represents a hypothesis of the model validity, which will then be confronted with 'reality' through clinical experiment. As the therapeutic model is refutable, clinical pharmacology is a science in the Popperian sense.

  20. A Blended Learning Course Design in Clinical Pharmacology for Post-graduate Dental Students

    Science.gov (United States)

    Rosenbaum, Paul-Erik Lillholm; Mikalsen, Øyvind; Lygre, Henning; Solheim, Einar; Schjøtt, Jan

    2012-01-01

    Postgraduate courses in clinical pharmacology are important for dentists to be updated on drug therapy and information related to their clinical practice, as well as knowledge of relevant adverse effects and interactions. A traditional approach with classroom delivery as the only method to teaching and learning has shortcomings regarding flexibility, individual learning preferences, and problem based learning (PBL) activities compared to online environments. This study examines a five week postgraduate course in clinical pharmacology with 15 hours of lectures and online learning activities, i.e. blended course design. Six postgraduate dental students participated and at the end of the course they were interviewed. Our findings emphasize that a blended learning course design can be successfully used in postgraduate dental education. Key matters for discussion were time flexibility and location convenience, change in teacher’s role, rein-forced learning strategies towards professional needs, scarcity in online communication, and proposed future utilization of e-learning components. PMID:23248716

  1. Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

    Science.gov (United States)

    Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

    2015-01-01

    Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety. © 2014 American Society for Clinical Pharmacology and Therapeutics.

  2. Effect of pre-rigor stretch and various constant temperatures on the rate of post-mortem pH fall, rigor mortis and some quality traits of excised porcine biceps femoris muscle strips.

    Science.gov (United States)

    Vada-Kovács, M

    1996-01-01

    Porcine biceps femoris strips of 10 cm original length were stretched by 50% and fixed within 1 hr post mortem then subjected to temperatures of 4 °, 15 ° or 36 °C until they attained their ultimate pH. Unrestrained control muscle strips, which were left to shorten freely, were similarly treated. Post-mortem metabolism (pH, R-value) and shortening were recorded; thereafter ultimate meat quality traits (pH, lightness, extraction and swelling of myofibrils) were determined. The rate of pH fall at 36 °C, as well as ATP breakdown at 36 and 4 °C, were significantly reduced by pre-rigor stretch. The relationship between R-value and pH indicated cold shortening at 4 °C. Myofibrils isolated from pre-rigor stretched muscle strips kept at 36 °C showed the most severe reduction of hydration capacity, while paleness remained below extreme values. However, pre-rigor stretched myofibrils - when stored at 4 °C - proved to be superior to shortened ones in their extractability and swelling.

  3. A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study.

    Science.gov (United States)

    Sabater, Lidia; Gaig, Carles; Gelpi, Ellen; Bataller, Luis; Lewerenz, Jan; Torres-Vega, Estefanía; Contreras, Angeles; Giometto, Bruno; Compta, Yaroslau; Embid, Cristina; Vilaseca, Isabel; Iranzo, Alex; Santamaría, Joan; Dalmau, Josep; Graus, Francesc

    2014-06-01

    Autoimmunity might be associated with or implicated in sleep and neurodegenerative disorders. We aimed to describe the features of a novel neurological syndrome associated with prominent sleep dysfunction and antibodies to a neuronal antigen. In this observational study, we used clinical and video polysomnography to identify a novel sleep disorder in three patients referred to the Sleep Unit of Hospital Clinic, University of Barcelona, Spain, for abnormal sleep behaviours and obstructive sleep apnoea. These patients had antibodies against a neuronal surface antigen, which were also present in five additional patients referred to our laboratory for antibody studies. These five patients had been assessed with polysomnography, which was done in our sleep unit in one patient and the recording reviewed in a second patient. Two patients underwent post-mortem brain examination. Immunoprecipitation and mass spectrometry were used to characterise the antigen and develop an assay for antibody testing. Serum or CSF from 298 patients with neurodegenerative, sleep, or autoimmune disorders served as control samples. All eight patients (five women; median age at disease onset 59 years [range 52-76]) had abnormal sleep movements and behaviours and obstructive sleep apnoea, as confirmed by polysomnography. Six patients had chronic progression with a median duration from symptom onset to death or last visit of 5 years (range 2-12); in four the sleep disorder was the initial and most prominent feature, and in two it was preceded by gait instability followed by dysarthria, dysphagia, ataxia, or chorea. Two patients had a rapid progression with disequilibrium, dysarthria, dysphagia, and central hypoventilation, and died 2 months and 6 months, respectively, after symptom onset. In five of five patients, video polysomnography showed features of obstructive sleep apnoea, stridor, and abnormal sleep architecture (undifferentiated non-rapid-eye-movement [non-REM] sleep or poorly structured

  4. Non-clinical models: validation, study design and statistical consideration in safety pharmacology.

    Science.gov (United States)

    Pugsley, M K; Towart, R; Authier, S; Gallacher, D J; Curtis, M J

    2010-01-01

    The current issue of the Journal of Pharmacological and Toxicological Methods (JPTM) focuses exclusively on safety pharmacology methods. This is the 7th year the Journal has published on this topic. Methods and models that specifically relate to methods relating to the assessment of the safety profile of a new chemical entity (NCE) prior to first in human (FIH) studies are described. Since the Journal started publishing on this topic there has been a major effort by safety pharmacologists, toxicologists and regulatory scientists within Industry (both large and small Pharma as well as Biotechnology companies) and also from Contract Research Organizations (CRO) to publish the surgical details of the non-clinical methods utilized but also provide important details related to standard and non-standard (or integrated) study models and designs. These details from core battery and secondary (or ancillary) drug safety assessment methods used in drug development programs have been the focus of these special issues and have been an attempt to provide validation of methods. Similarly, the safety pharmacology issues of the Journal provide the most relevant forum for scientists to present novel and modified methods with direct applicability to determination of drug safety-directly to the safety pharmacology scientific community. The content of the manuscripts in this issue includes the introduction of additional important surgical methods, novel data capture and data analysis methods, improved study design and effects of positive control compounds with known activity in the model. Copyright 2010 Elsevier Inc. All rights reserved.

  5. Analysis of the Chemical, Pharmacological and Clinical Applications of Polygonum Cuspidatum

    Science.gov (United States)

    Guo, Chenyang; Bai, Ming; Miao, Mingsan; Miao, Yanyan

    2018-01-01

    Traditional Chinese medicine Polygonum cuspidatum widely used, the larger production, and in the clinical application of more, but the role played by the role of different roles are also different. By reviewing the relevant literatures in recent years, the chemical constituents and pharmacological effects of Polygonum cuspidatum were sorted and summarized, and the role of Polygonum cuspidatum was analyzed, and the function of Polygonum cuspidatum was explored to find out the role of Polygonum cuspidatum in compatibility. Application law. Which can not only study the medicinal mechanism of Polygonum cuspidatum, but also provide the theoretical basis for the medicinal development, clinical treatment and comprehensive utilization of Polygonum cuspidatum.

  6. Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use.

    Science.gov (United States)

    Taylor, Charles P; Traynelis, Stephen F; Siffert, Joao; Pope, Laura E; Matsumoto, Rae R

    2016-08-01

    Dextromethorphan (DM) has been used for more than 50years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-d-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential. DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide and quinidine sulfate (DM/Q), with subsequent approval by the US Food and Drug Administration for pseudobulbar affect, led to renewed interest in understanding DM pharmacology. This review summarizes the interactions of DM with brain receptors and transporters and also considers its metabolic and pharmacokinetic properties. To assess the potential clinical relevance of these interactions, we provide an analysis comparing DM activity from in vitro functional assays with the estimated free drug DM concentrations in the brain following oral DM/Q administration. The findings suggest that DM/Q likely inhibits serotonin and norepinephrine reuptake and also blocks NMDA receptors with rapid kinetics. Use of DM/Q may also antagonize nicotinic acetylcholine receptors, particularly those composed of α3β4 subunits, and cause agonist activity at sigma-1 receptors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. [Macroscopical estimation of the post mortem interval (PMI) and exclusion of the forensically relevant resting period--a comparison of data presented in the literature with recent osteological findings].

    Science.gov (United States)

    Holley, Stephanie; Fiedler, Sabine; Graw, Matthias

    2008-01-01

    The aim of the present study was to determine to what extent macroscopical parameters mentioned in the literature are suitable for the estimation of the post mortem interval (PMI) and particularly for the exclusion of the forensically relevant resting period for recent bone material. The macroscopical examination of recent bone material with a known PMI showed that only one published parameter (relics of adipocere in the cross section of the compacta) was consistent with our findings for this particular resting period (27-28 years). Other macroscopical parameters presented in the literature were contradictory to the results observed in this study. Among those are the rigidity of bones, the adhesion of soft tissue, the filling of the marrow cavity, and the permeation of the epiphyses with adipocere. Concerning the exclusion of the forensically relevant resting period, a similar result was observed. This study identified some diagnostic findings in bones with a resting period of less than 50 years which according to the literature should only be present after a resting period of more than 50 years. These features included the lack of macroscopical traces of adipocere, degradation of the compacta surface, detachment of the cortical substance, the ability of bone to be broken with bare hands, and superficial usures. Moreover, in one-third of our cases we identified some intra-individual differences not previously described in the literature. In addition to the other results, those intra-individual differences make an estimation of the PMI more difficult. However it should be noted that those published parameters were collected from bone material which was stored in a "relatively arid sand-grit-clay soil of the broken stone layer of Munich". The bones in the present study were stored in acidic and clayey-loamy soil, partly with lateral water flow. In conclusion, the present study demonstrates that one should use caution estimating the post mortem interval and excluding

  8. Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral sclerosis and in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.

    Science.gov (United States)

    De Reuck, Jacques; Devos, David; Moreau, Caroline; Auger, Florent; Durieux, Nicolas; Deramecourt, Vincent; Pasquier, Florence; Maurage, Claude-Alain; Cordonnier, Charlotte; Leys, Didier; Bordet, Regis

    2017-12-01

    Amyotrophic lateral sclerosis (ALS) is associated with frontotemporal lobar degeneration (FTLD) in 15% of the cases. A neuropathological continuity between ALS and FTLD-TDP is suspected. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) study compares the topographic distribution of iron (Fe) deposition and the incidence of small cerebrovascular lesions in ALS and in FTLD brains. Seventy-eight post-mortem brains underwent 7.0-tesla MRI. The patients consisted of 12 with ALS, 38 with FTLD, and 28 controls. Three ALS brains had minor FTLD features. Three coronal sections of a cerebral hemisphere were submitted to T2 and T2* MRI sequences. The amount of Fe deposition in the deep brain structures and the number of small cerebrovascular lesions was determined in ALS and the subtypes of FTLD compared to control brains, with neuropathological correlates. A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei. White matter changes were only significantly more severe in the FTLD compared to those in ALS and in controls brains. Cortical micro-bleeds were increased in the frontal and temporal lobes of FTLD as well as of ALS brains compared to controls. Cortical micro-infarcts were, on the other hand, more frequent in the control compared to the ALS and FTLD groups. The present study supports the assumption of a neuropathological continuity between ALS and FTLD and illustrates the favourable vascular risk profile in these diseases.

  9. [History of clinical pharmacology in France: adaptation, evaluation, defense and illustration of drug in France 1978-1981].

    Science.gov (United States)

    Montastruc, Paul

    2014-01-01

    This text illustrates some unknown aspects of the history and beginnings of clinical pharmacology in France in the late 1970s and early 1980s From the current situation, development and objectives of clinical pharmacology are recalled as well as obstacles necessary to overcome to change the paradigm in the field of drug evaluation and appropriate use in France. The text recalls this important moment where French medicine and medical pharmacology entered the modern era. © 2014 Société Française de Pharmacologie et de Thérapeutique.

  10. Overview of clinical efficacy and safety of pharmacologic strategies for blood conservation.

    Science.gov (United States)

    Levy, Jerrold H

    2005-09-15

    The pharmacologic management of hemostasis in patients undergoing surgery with cardiopulmonary bypass is discussed. Nearly 45 studies involving 7,000 patients have reported efficacy of aprotinin in blood conservation. Both in primary coronary artery bypass graft (CABG) surgeries and in repeat surgeries, aprotinin treatment significantly reduces the incidence of blood transfusions and the number of units of blood transfused. These effects have been observed for red blood cell, platelet, and other blood products. The safety of aprotinin treatment has been extensively evaluated in randomized clinical trials, in postmarketing databases, and in systematic reviews of the literature. Overall, data do not indicate that aprotinin treatment increases mortality, myocardial infarction, or renal failure. These findings are supported by the results of a recent meta-analysis of 35 studies in patients undergoing CABG surgery. In addition, the meta-analysis suggests that aprotinin treatment was associated with a reduced incidence of stroke and a trend toward a reduced incidence of atrial fibrillation. Although lysine analogs, desmopressin, and recombinant factor VIIa are sometimes used to reduce bleeding, only aprotinin is indicated for use during CABG surgery. The future of cardiac surgery will be marked by an increasingly complex, high-risk group of patients and a greater need for multiple pharmacologic options for reducing bleeding. Pharmacologic approaches that attenuate the activation of the hemostatic system and inflammation need to be employed to decrease coagulopathies and the need for allogeneic blood administration.

  11. Have the Findings from Clinical Risk Prediction and Trials Any Key Messages for Safety Pharmacology?

    Directory of Open Access Journals (Sweden)

    Jem D. Lane

    2017-11-01

    Full Text Available Anti-arrhythmic drugs are a mainstay in the management of symptoms related to arrhythmias, and are adjuncts in prevention and treatment of life-threatening ventricular arrhythmias. However, they also have the potential for pro-arrhythmia and thus the prediction of arrhythmia predisposition and drug response are critical issues. Clinical trials are the latter stages in the safety testing and efficacy process prior to market release, and as such serve as a critical safeguard. In this review, we look at some of the lessons to be learned from approaches to arrhythmia prediction in patients, clinical trials of drugs used in the treatment of arrhythmias, and the implications for the design of pre-clinical safety pharmacology testing.

  12. Clinical pharmacology quality assurance program: models for longitudinal analysis of antiretroviral proficiency testing for international laboratories.

    Science.gov (United States)

    DiFrancesco, Robin; Rosenkranz, Susan L; Taylor, Charlene R; Pande, Poonam G; Siminski, Suzanne M; Jenny, Richard W; Morse, Gene D

    2013-10-01

    Among National Institutes of Health HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals. Drug assay data are, in turn, entered into study-specific data sets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis, and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semiannual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1) assess the precision and accuracy of concentrations reported by individual CPLs and (2) determine factors associated with round-specific and long-term assay accuracy, precision, and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21) drug concentration results reported for clinical trial samples by multiple CPLs). Using the Clinical Laboratory Improvement Act acceptance of meeting criteria for ≥2/3 consecutive rounds, all 10 laboratories that participated in 3 or more rounds per analyte maintained Clinical Laboratory Improvement Act proficiency. Significant associations were present between magnitude of error and CPL (Kruskal-Wallis P Kruskal-Wallis P < 0.001).

  13. Differential clinical pharmacology of rolapitant in delayed chemotherapy-induced nausea and vomiting (CINV

    Directory of Open Access Journals (Sweden)

    Rashad N

    2017-03-01

    Full Text Available Noha Rashad,1 Omar Abdel-Rahman2 1Medical Oncology Department, Maadi Armed Forces Hospital, 2Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: Rolapitant is a highly selective neurokinin-1 receptor antagonist, orally administered for a single dose of 180 mg before chemotherapy with granisetron D1, dexamethasone 8 mg BID on day 2–4. It has a unique pharmacological characteristic of a long plasma half-life (between 163 and 183 hours; this long half-life makes a single use sufficient to cover the delayed emesis risk period. No major drug–drug interactions between rolapitant and dexamethasone or other cytochrome P450 inducers or inhibitors were observed. The clinical efficacy of rolapitant was studied in two phase III trials in highly emetogenic chemotherapy and in one clinical trial in moderately emetogenic chemotherapy. The primary endpoint was the proportion of patients achieving a complete response (defined as no emesis or use of rescue medication in the delayed phase (>24–120 hours after chemotherapy. In comparison to granisetron (10 µg/kg intravenously and dexamethasone (20 mg orally on day 1, and dexamethasone (8 mg orally twice daily on days 2–4 and placebo, rolapitant showed superior efficacy in the control of delayed and overall emesis. This review aims at revising the pharmacological characteristics of rolapitant, offering an updated review of the available clinical efficacy and safety data of rolapitant in different clinical settings, highlighting the place of rolapitant in the management of chemotherapy-induced nausea and vomiting (CINV among currently available guidelines, and exploring the future directions of CINV management. Keywords: nausea, vomiting, chemotherapy, rolapitant, CINV

  14. Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

    Science.gov (United States)

    Huard, J; Mu, X; Lu, A

    2016-08-01

    Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  15. The mollusks in zootherapy: traditional medicine and clinical-pharmacological importance

    Directory of Open Access Journals (Sweden)

    Eraldo Medeiros Costa Neto

    2006-09-01

    Full Text Available The use of animals as sources of medicines is a cross-cultural phenomenon that is historically ancient and geographically widespread. This article reviews the use of mollusks in traditional medicine and discusses the clinical and pharmacological importance of these invertebrates. The roles that mollusks play in folk practices related to the healing and/or prevention of illnesses have been recorded in different social-cultural contexts worldwide. The clinical and therapeutic use of compounds coming from different species of mollusks is recorded in the literature. The chemistry of natural products provided by oysters, mussels, clams, sluggards, and snails has been substantially investigated, but the majority of these studies have focused on the subclasses Opistobranchia and Prosobranchia. Research into the knowledge and practices of folk medicine makes possible a better understanding of the interaction between human beings and the environment, in addition to allowing the elaboration of suitable strategies for the conservation of natural resources.

  16. CLINICAL AND PHARMACOLOGICAL PECULIARITIES OF CETIRIZINE USE FOR THE THERAPY OF ALLERGIC DISEASES IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Yu. G. Levina

    2014-01-01

    Full Text Available The review is dedicated to treatment of allergic diseases in children, particularly to the use of the 2nd generation antihistamine. It demonstrates that mediator histamine has the crucial role in pathophysiology of the allergic reaction. Antihistamines block histamine action aimed at H1 receptors by way of competitive inhibition. The 2nd generation antihistamines are the drugs of choice for the treatment of allergic diseases due to the absence of sedative effect. The review presents clinical and pharmacological description of the selective 2nd generation antihistamine cetirizine, efficacy and safety of which have been appraised in numerous long-term clinical studies in children with allergic rhinitis, urticaria and atopic dermatitis. 

  17. Clinical pharmacology of CAR-T cells: Linking cellular pharmacodynamics to pharmacokinetics and antitumor effects.

    Science.gov (United States)

    Norelli, M; Casucci, M; Bonini, C; Bondanza, A

    2016-01-01

    Adoptive cell transfer of T cells genetically modified with tumor-reactive chimeric antigen receptors (CARs) is a rapidly emerging field in oncology, which in preliminary clinical trials has already shown striking antitumor efficacy. Despite these premises, there are still a number of open issues related to CAR-T cells, spanning from their exact mechanism of action (pharmacodynamics), to the factors associated with their in vivo persistence (pharmacokinetics), and, finally, to the relative contribution of each of the two in determining the antitumor effects and accompanying toxicities. In light of the unprecedented curative potential of CAR-T cells and of their predicted wide availability in the next few years, in this review we will summarize the current knowledge on the clinical pharmacology aspects of what is anticipated to be a brand new class of biopharmaceuticals to join the therapeutic armamentarium of cancer doctors. Copyright © 2015. Published by Elsevier B.V.

  18. Review of Clinical Pharmacology of Aloe vera L. in the Treatment of Psoriasis.

    Science.gov (United States)

    Miroddi, Marco; Navarra, Michele; Calapai, Fabrizio; Mancari, Ferdinando; Giofrè, Salvatore Vincenzo; Gangemi, Sebastiano; Calapai, Gioacchino

    2015-05-01

    Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune-mediated chronic inflammatory disease, involving mainly the skin, affects about the 2-3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Methamphetamine: An Update on Epidemiology, Pharmacology, Clinical Phenomenology, and Treatment Literature

    Science.gov (United States)

    Courtney, Kelly E.; Ray, Lara A.

    2014-01-01

    Background Despite initial reports of a decline in use in the early 2000s, methamphetamine remains a significant public health concern with known neurotoxic and neurocognitive effects to the user. The goal of this review is to update the literature on methamphetamine use and addiction since its assent to peak popularity in 1990s. Methods Specifically, we first review recent epidemiological reports with a focus on methamphetamine accessibility, changes in use and disorder prevalence rates over time, and accurate estimates of the associated burden of care to the individual and society. Second, we review methamphetamine pharmacology literature with emphasis on the structural and functional neurotoxic effects associated with repeated use of the drug. Third, we briefly outline the findings on methamphetamine-related neurocognitive deficits as assessed via behavioral and neuroimaging paradigms. Lastly, we review the clinical presentation of methamphetamine addiction and the evidence supporting the available psychosocial and pharmacological treatments within the context of an addiction biology framework. Conclusion Taken together, this review provides a broad-based update of the available literature covering methamphetamine research over the past two decades and concludes with recommendations for future research. PMID:25176528

  20. Carthami flos: a review of its ethnopharmacology, pharmacology and clinical applications

    Directory of Open Access Journals (Sweden)

    Yanhua Tu

    Full Text Available ABSTRACTCarthami flos, the dried floret of Carthamus tinctorius L., Asteraceae (safflower, has been widely used in traditional Chinese medicine to treat a broad range of ailments, such as coronary heart disease, angina pectoris, gynecologic disease, stroke, and hypertension. However, although several studies on Carthami flos have been done consecutively, the results are usually scattered across various documents. This review aims to provide up-to-date information on the traditional uses, pharmacology, clinical applications, and toxicology of Carthami flos in China and thereby to provide a basis for further investigation of its use to treat dissimilar diseases. Various ethnomedical uses of Carthami flos have been documented in many ancient Chinese books. Crude extracts and isolated compounds from Carthami flos show a broad range of pharmacological properties, such as protective effects on brain tissue, on osteoblasts, and in myocardial ischemia, as well as anti-inflammatory, antithrombotic, antitumor, and antidiabetic activities. To date, safflower and safflor yellow injections have been used to treat coronary heart disease, chronic pulmonary heart disease, cerebrovascular diseases, orthopedic diseases, and diabetes mellitus. Regarding the toxicology of Carthami flos, among the side effects that have been observed are allergic reaction, spermatogenetic failure, fatty liver, and nephrotoxicity.

  1. Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology.

    Science.gov (United States)

    Ferner, Robin E; Aronson, Jeffrey K

    2016-01-01

    We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration-effect curves, dose-response curves, and ligand-receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson-Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions. © 2015 The British Pharmacological Society.

  2. CLINICAL-PHARMACOLOGICAL VALUE OF TREATMENT EFFICIENCY OF BHP-PATIENTS BY ANTITHROMBOTIC THERAPY

    Directory of Open Access Journals (Sweden)

    A.A. Svistunov

    2007-09-01

    Full Text Available Patients with BHP need in pharmacological treatment of thrombosis the most often in the first 3 cases because has dysfunctions of platelets and coagulation. According to results of analysis of efficiency antithrombotic therapy in BHP-patients confirmed clinical and biochemical influence antithrombotic therapy by Ticlid 250 mg twice on the day in comparison with Aspirin 100 mg and Dipiridomol 25 mg on the basic therapy of the BHP by Permixon 160 mg. The received results have had statistically meant differences. Manifestation of BHP and value QOL and others urodynamic complications most often appear on the basic specific monotherapy of BHP and lost after antithrombotic therapy for 1-3 months. The important complications of antithrombotic therapy of BHP-patients did not observe.

  3. Clinical inertia in the pharmacological management of hypertension: A systematic review and meta-analysis.

    Science.gov (United States)

    Milman, Tal; Joundi, Raed A; Alotaibi, Naif M; Saposnik, Gustavo

    2018-06-01

    Clinical Inertia is defined as "failure of health care providers to initiate or intensify therapy according to current guidelines". This phenomenon is gaining increasing attention as a major cause of clinicians' failure to adequately manage hypertension, thus leading to an increased incidence of cardiovascular events. We performed a systematic review and meta-analysis of randomized controlled trials to determine whether interventions aimed at reducing clinical inertia in the pharmacological treatment of hypertension improve blood pressure (BP) control. MEDLINE, Embase, and Cochrane Database of Systematic Reviews were searched from the start of their database until October 3, 2017 for the MESH terms "Hypertension" or "Blood Pressure", their subheadings, and the keywords "Therapeutic Inertia" or "Clinical Inertia". Studies were included if they addressed pharmacologic hypertension management, clinical inertia, were randomized controlled trials, reported an outcome describing prescriber behavior, and were available in English. Data for the included studies was extracted by two independent observers. Quality of studies was analyzed using the Cochrane Risk of Bias Assessment. Data was pooled for statistical analysis using both fixed- and random-effects models. The primary study outcome was the percentage of patients achieving blood pressure control as defined by the Joint National Committee guidelines or study authors. Of 474 citations identified, ten met inclusion criteria comprising a total of 26,871 patients, and eight were selected for meta-analysis. Interventions included Physician Education, Physician Reminders, Patient Education, Patient Reminders, Ambulatory BP Monitoring, Digital Medication Offerings, Physician Peer Visits, and Pharmacist-led Counselling. Pooled event rates revealed more patients with controlled BP in the intervention group versus control (55%, 95% CI 46-63% versus 45%, 95% CI 37-53%) and interventions significantly improved the odds of BP

  4. Evaluation of the efficiency of nested q-PCR in the detection of Mycobacterium tuberculosis complex directly from tuberculosis-suspected lesions in post-mortem macroscopic inspections of bovine carcasses slaughtered in the state of Mato Grosso, Brazil.

    Science.gov (United States)

    Carvalho, Ricardo César Tavares; Furlanetto, Leone Vinícius; Maruyama, Fernanda Harumy; Araújo, Cristina Pires de; Barros, Sílvia Letícia Bomfim; Ramos, Carlos Alberto do Nascimento; Dutra, Valéria; Araújo, Flábio Ribeiro de; Paschoalin, Vânia Margaret Flosi; Nakazato, Luciano; Figueiredo, Eduardo Eustáquio de Souza

    2015-08-01

    Bovine tuberculosis (BTB) is a zoonotic disease caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTC). The quick and specific detection of this species is of extreme importance, since BTB may cause economic impacts, in addition to presenting imminent risks to human health. In the present study a nested real-time PCR test (nested q-PCR) was used in post-mortem evaluations to assess cattle carcasses with BTB-suspected lesions. A total of 41,193 cattle slaughtered in slaughterhouses located in the state of Mato Grosso, were examined. Of the examined animals, 198 (0.48%) showed BTB-suspected lesions. M. bovis was isolated in 1.5% (3/198) of the samples. Multiplex-PCR detected MTC in 7% (14/198) of the samples. The nested q-PCR test detected MTC in 28% (56/198) of the BTB-suspected lesions, demonstrating higher efficiency when compared to the multiplex-PCR and conventional microbiology. Nested q-PCR can therefore be used as a complementary test in the national program for control and eradication of bovine tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Hard x-ray micro-tomography of a human head post-mortem as a gold standard to compare X-ray modalities

    DEFF Research Database (Denmark)

    Dalstra, Michel; Schulz, Georg; Dagassan-Berndt, Dorothea

    2016-01-01

    in a larger study comparing the image quality of various cone beam CT systems currently used in dentistry. The image quality of the micro-CT scans was indeed better than the ones of the clinical imaging modalities, both with regard to noise and streak artifacts due to metal dental implants. Bony features...

  6. Clinically Relevant Pharmacological Strategies That Reverse MDMA-Induced Brain Hyperthermia Potentiated by Social Interaction.

    Science.gov (United States)

    Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin

    2016-01-01

    MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.

  7. Pharmacological profile of β3-adrenoceptor agonists in clinical development for the treatment of overactive bladder syndrome

    NARCIS (Netherlands)

    Igawa, Yasuhiko; Michel, Martin C.

    2013-01-01

    β(3)-Adrenoceptor agonists are an emerging drug class for the treatment of the overactive bladder syndrome, and clinical proof-of-concept data have been obtained for three representatives of this class, mirabegron, ritobegron, and solabegron. We review here the pharmacological profile of these three

  8. European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

    DEFF Research Database (Denmark)

    Roessner, Veit; Plessen, Kerstin J; Rothenberger, Aribert

    2011-01-01

    provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary...

  9. Guanidino-containing drugs in cancer chemotherapy: biochemical and clinical pharmacology.

    Science.gov (United States)

    Ekelund, S; Nygren, P; Larsson, R

    2001-05-15

    The pharmacology and clinical application of three guanidino-containing compounds are reviewed in this commentary with special focus on a new member of this group of drugs, CHS 828 [N-(6-(4-chlorophenoxy)hexyl)-N'-cyano-N"-4-pyridylguanidine]. m-Iodobenzylguanidine (MIBG) and methylglyoxal bis(guanylhydrazone) (MGBG) have been extensively studied, preclinically as well as clinically, and have established use as anticancer agents. MIBG has structural similarities to the neurotransmitter, norepinephrine, and MGBG is a structural analog of the natural polyamine spermidine. CHS 828 is a pyridyl cyanoguanidine newly recognized as having cytotoxic effects when screening antihypertensive compounds. Apart from having the guanidino groups in common, there are many differences between these drugs in both structure and their mechanisms of action. However, they all inhibit mitochondrial function, a seemingly unique feature among chemotherapeutic drugs. In vitro in various cell lines and primary cultures of patient tumor cells and in vivo in various tumor models, CHS 828 has cytotoxic properties unlike any of the standard cytotoxic drugs with which it has been compared. Among these are non-cross-resistance to standard drugs and pronounced activity in tumor models acknowledged to be highly drug-resistant. Similar to MIBG, CHS 828 induces an early increase in extracellular acidification, due to stimulation of the glycolytic flux. Furthermore, ATP levels decrease, and the syntheses of DNA and protein are shut off after approximately 30 hr of exposure, indicating active cell death. CHS 828 is now in early clinical trials, the results of which are eagerly awaited.

  10. Post-mortem inference of the human hippocampal connectivity and microstructure using ultra-high field diffusion MRI at 11.7 T.

    Science.gov (United States)

    Beaujoin, Justine; Palomero-Gallagher, Nicola; Boumezbeur, Fawzi; Axer, Markus; Bernard, Jeremy; Poupon, Fabrice; Schmitz, Daniel; Mangin, Jean-François; Poupon, Cyril

    2018-06-01

    The human hippocampus plays a key role in memory management and is one of the first structures affected by Alzheimer's disease. Ultra-high magnetic resonance imaging provides access to its inner structure in vivo. However, gradient limitations on clinical systems hinder access to its inner connectivity and microstructure. A major target of this paper is the demonstration of diffusion MRI potential, using ultra-high field (11.7 T) and strong gradients (750 mT/m), to reveal the extra- and intra-hippocampal connectivity in addition to its microstructure. To this purpose, a multiple-shell diffusion-weighted acquisition protocol was developed to reach an ultra-high spatio-angular resolution with a good signal-to-noise ratio. The MRI data set was analyzed using analytical Q-Ball Imaging, Diffusion Tensor Imaging (DTI), and Neurite Orientation Dispersion and Density Imaging models. High Angular Resolution Diffusion Imaging estimates allowed us to obtain an accurate tractography resolving more complex fiber architecture than DTI models, and subsequently provided a map of the cross-regional connectivity. The neurite density was akin to that found in the histological literature, revealing the three hippocampal layers. Moreover, a gradient of connectivity and neurite density was observed between the anterior and the posterior part of the hippocampus. These results demonstrate that ex vivo ultra-high field/ultra-high gradients diffusion-weighted MRI allows the mapping of the inner connectivity of the human hippocampus, its microstructure, and to accurately reconstruct elements of the polysynaptic intra-hippocampal pathway using fiber tractography techniques at very high spatial/angular resolutions.

  11. Differential pharmacology and clinical utility of rolapitant in chemotherapy-induced nausea and vomiting

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    Rapoport BL

    2017-02-01

    Full Text Available Bernardo Leon Rapoport The Medical Oncology Centre of Rosebank, Johannesburg, South Africa Abstract: Chemotherapy-induced nausea and vomiting (CINV is a debilitating side effect of many cytotoxic chemotherapy regimens. CINV typically manifests during two well-defined time periods (acute and delayed phases. The acute phase is the first 24 hours after chemotherapy and is largely managed with 5-hydroxytryptamine 3 receptor antagonists. The delayed phase, a 5-day at-risk period during which patients are not often in direct contact with their health care provider, remains a significant unmet medical need. Neurokinin-1 (NK-1 receptor antagonists have demonstrated protection against acute and delayed CINV in patients treated with highly emetogenic chemotherapy and moderately emetogenic chemotherapy when used in combination with a 5-hydroxytryptamine 3 receptor antagonist and dexamethasone. Furthermore, recent data indicate that this protection is maintained over multiple treatment cycles. Rolapitant, a selective and long-acting NK-1 receptor antagonist, is approved as oral formulation for the prevention of delayed CINV in adults. This review discusses the differential pharmacology and clinical utility of rolapitant in preventing CINV compared with other NK-1 receptor antagonists. Keywords: antiemetics, highly emetogenic chemotherapy, moderately emetogenic chemotherapy, delayed chemotherapy-induced nausea and vomiting, emesis, neurokinin-1 receptor antagonists

  12. [Clinical subtypes of essential tremor and their electrophysiological and pharmacological differences].

    Science.gov (United States)

    Koguchi, Y; Nakajima, M; Kawamura, M; Hirayama, K

    1995-02-01

    We divided 19 patients with essential tremor into two subtypes according to clinical characteristics of the tremor. Ten patients had pure postural tremor distributed in the hand(s), head, and face (group A). Nine patients had tremor extending to the voice or leg(s), associated with resting tremor and/or hyperkinesie volitionnelle of the hand(s) (group B). Their ages, the age of onset, and the duration of illness were not different between the two groups. Electrophysiologically, the tremor of group A patients had higher frequencies than that of group B patients, and had synchronized activities for antagonistic muscles. Four of group B patients had reciprocal antagonistic activities of the tremor. Inactive phase of tremor induced by an electrically-evoked muscle twitch was invariably within the range of the physiological silent period for group A patients, and prolonged beyond the range for four of group B patients. Pharmacologically, 78% of group A patients responded well to beta-blocker, which was effective for 25% of group B patients. Sixty per cent of beta-blocker-resistant group B patients responded well to phenobarbital. In conclusion, a peripheral mechanism, presumably beta-adrenergic drive, is important for the tremor in group A patients, while central pathogenic mechanisms are more important for the tremor of group B patients.

  13. Avanafil for erectile dysfunction in elderly and younger adults: differential pharmacology and clinical utility

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    Katz EG

    2014-08-01

    Full Text Available Eric G Katz,1 Ronny BW Tan,2 Daniel Rittenberg,1 Wayne J Hellstrom3 1Tulane University School of Medicine, New Orleans, LA, USA; 2Department of Urology, Tan Tock Seng Hospital, Singapore; 3Section of Andrology, Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA Abstract: The treatment modalities of erectile dysfunction range from oral pharmacotherapy to intracavernosal injections, intraurethral pellets, vacuum erectile devices, and the surgical option of penile prosthesis insertion. Oral phosphodiesterase 5 inhibitors still remain the preferred treatment for patients since they are the least invasive, not to mention that they can be prescribed by non-urologists. Due to these factors, there has been development of newer drugs with fewer side effects. This is a review of the second generation phosphodiesterase 5 inhibitor, avanafil, looking into its pharmacology as well as its clinical utility. Avanafil's faster onset and shorter duration of action has made it preferred as compared to other PDE5 inhibitors for patients with multiple comorbidities. Keywords: phosphodiesterase 5 inhibitors, impotence, sildenafil, sexual dysfunction, nitric oxide

  14. The retinoids. A review of their clinical pharmacology and therapeutic use.

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    Orfanos, C E; Ehlert, R; Gollnick, H

    1987-10-01

    With the introduction of the synthetic retinoids, oral therapy with an acceptable risk/benefit ratio became possible for a variety of skin diseases including severe acne, psoriasis and numerous genodermatoses. This article reviews the clinical pharmacology, mechanisms of action and therapeutic use of the retinoids, particularly isotretinoin (13-cis-retinoic acid) and etretinate. The free aromatic acid of etretinate, etretin, and the new polyaromatic retinoid compounds (arotinoids) are also discussed. Isotretinoin is used clinically for oral therapy of severe acne, but is also recommended for severe Gram-negative folliculitis and rosacea not responding to traditional therapy. The results of several studies have established that acne therapy should be started with 1.0 mg/kg/day for 2 to 3 months after which the daily dosage should be lowered to 0.2 to 0.5 mg/kg/day for another 2 to 3 months. This therapeutic regimen of isotretinoin has proven to be the most successful in preventing relapses. Etretinate is particularly useful for oral therapy of widespread plaque-like, pustular and erythrodermic psoriasis, and of generalised lichen planus, Darier's disease and severe congenital ichthyoses. Whereas pustular forms of psoriasis require a high daily dosage of 1.0 mg/kg/day, erythrodermic psoriasis should be treated with a lower dosage of 0.25 to 0.35 mg/kg/day. In chronic plaque-like psoriasis, a mean daily dosage of 0.5 mg/kg/day over several weeks to months, usually combined with photo(chemo)therapy, tar or dithranol, is recommended. Other indications for oral etretinate therapy are adequately treated with a moderate dosage of 0.4 to 0.75 mg/kg/day. Etretin differs from etretinate in having a much shorter elimination half-life of 2 to 3 days, in contrast to 80 to 100 days after long term administration of etretinate. Moreover, it has not been shown to increase serum cholesterol levels. However, its clinical efficacy is not yet clearly established. Among the arotinoids

  15. Isolation and determination of ivermectin in post-mortem and in vivo tissues of dung beetles using a continuous solid phase extraction method followed by LC-ESI+-MS/MS.

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    Antonio J Ortiz

    Full Text Available A new analytical method based on solvent extraction, followed by continuous solid-phase extraction (SPE clean-up using a polymeric sorbent, was demonstrated to be applicable for the detection of ivermectin in complex biological matrices of dung beetles (hemolymph, excreta or dry tissues using liquid chromatography combined with positive electrospray ionization tandem mass spectrometry (LC/ESI+-MS/MS. Using a signal-to-noise ratio of 3:1, the limit of detection (LOD in the insect matrices at trace levels was 0.01 ng g-1 and the limit of quantification (LOQ was 0.1 ng g-1. The proposed method was successfully used to quantitatively determine the levels of ivermectin in the analysis of small samples in in vivo and post mortem samples, demonstrating the usefulness for quantitative analyses that are focused on future pharmacokinetic and bioavailability studies in insects and the establishment of a new protocol to study the impact of ivermectin on non-target arthropods such as dung beetles and other insects that are related with the "dung community". Because satisfactory precision and accuracy values were obtained in both in vivo matrices, we suggest that the method can be consistently used for quantitative determinations that are focused on future pharmacokinetic and bioavailability studies in insects. Furthermore, this new analytical method was successfully applied to biological samples of dead dung beetles from the field suggesting that the method can be used to establish a new routine analysis of ivermectin residues in insect carcasses that is applied to complement typical mortality tests.

  16. Comparación de la técnica de Dennis con los hallazgos hepáticos post - mortem para el diagnóstico de la fasciolosis bovina

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    Alejandra Alvarez

    2009-10-01

    Full Text Available El presente estudio hace una comparación entre los resultados de la técnica de Dennis para diagnóstico de Fasciolosis bovina, frente a hallazgos post mortem, en hígados de bovinos faenados en la empresa Matadero de Tunja. Es un estudio experimental descriptivo, por cuanto expone los hallazgos en matadero frente a los arrojados por el método de Dennis. La población total de bovinos adultos fue de 2800, de los cuales se tomó una muestra de 139 animales. El muestreo se llevó a cabo durante el mes de febrero del año 2009. Los resultados indican que la técnica de Dennis no es lo suficientemente sensible para el diagnóstico de Fasciola hepática, por lo que se debe evaluar su uso rutinario.La técnica coprológica se fundamenta en el principio de sedimentación delos huevos, por lo tanto depende la salida de éstos en la materia fecal, lo que la hace poco efectiva para la detección del parásito. La razón de este estudiose sustenta en que la enfermedad se encuentra ampliamente distribuida en la región y en el país. Su diagnóstico se realiza rutinariamente mediante técnicas coprológicas aplicadas a los animales en los que se sospecha la enfermedad.

  17. SU-C-12A-04: Diagnostic Imaging Research Using Decedents as a Proxy for the Living: Are Radiation Dosimetry and Tissue Property Measurements Affected by Post-Mortem Changes?

    Energy Technology Data Exchange (ETDEWEB)

    Sandoval, D; Heintz, P [Department of Radiology University of New Mexico School of Medicine, Albuquerque, NM (United States); Weber, W; Melo, D [Lovelace Respiratory Research Institute, Albuquerque, New Mexico (United States); Adolphi, N; Hatch, P [Radiology-Pathology Center for Forensic Imaging, University of New Mexico School of Medicine, Albuquerque, New Mexico (United States)

    2014-06-01

    Purpose: Radiation dose (RD) from diagnostic imaging is a growing public health concern. Implanting dosimeters is a more accurate way to assess organ dose, relative to commonly used mathematical estimations. However, performing accurate dosimetry using live subjects is hindered by patient motion and safety considerations, which limit the RD and placement of implanted dosimeters. Performing multiple scans on the same subject would be the ideal way to assess the impact of dose reduction on image quality; however, performing multiple non-standard-of-care scans on live subjects for dosimetry and image quality measurements is generally prohibited by IRB committees. Our objective is to assess whether RD and tissue property (TP) measurements in post-mortem (PM) subjects are sufficiently similar to those in live subjects to justify the use of deceased subjects in future dosimetry and image quality studies. Methods: 4 MOSFET radiation dosimeters were placed enterically in each subject (2 sedated Rhesus Macaques) to measure the RD at 4 levels (carina, lung, heart, and liver) during CT scanning. The CT protocol was performed ante-mortem (AM) and 2 and 3 hours PM. For TP analysis, additional scans were taken at 24 hours PM. To compare AM and PM TP, regions-of-interest were drawn on selected organs and the average CT density with standard deviation (in units of HU) were taken; additionally, visual comparisons of images were made at each PM interval. Results: No significant difference was observed in 8 of 9 measurements comparing AM and PM RD. Only one measurement (liver of the first subject) showed a significant difference (7% lower on PM measurement), possibly due to subject re-positioning. Initial TP visual and quantitative analyses show little to no change PM. Conclusion: Our results suggest that realistic radiation dosimetry and image quality measurements based on tissue properties can be performed reliably on recently deceased subjects.

  18. Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals - a proof of concept study.

    Science.gov (United States)

    Sheldrick, A; Camara, S; Ilieva, M; Riederer, P; Michel, T M

    2017-10-01

    The neurotrophic factors (NTF) hypothesis of depression was postulated nearly a decade ago and is nowadays widely acknowledged. Previous reports suggest that cerebral concentrations of NTF may be reduced in suicide victims who received minimal or no antidepressant pharmacotherapy. Recent evidence suggests that antidepressant treatment may improve or normalise cerebral concentrations of neurotrophic factors. Therefore, we examined the concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in different brain regions (cortex, cingulate gyrus, thalamus, hippocampus, putamen and nucleus caudatus) of 21 individuals - 7 patients of which 4 patients with major depressive disorder (MDD) and overall age 86.8±5 years who received antidepressant pharmacotherapy (selective serotonin re-uptake inhibitors [SSRI]; tricyclic antidepressants [TCA]), 3 patients with MDD without antidepressant treatment and overall age 84.3±5 years versus 14 unaffected subjects at age 70.3±13.8. We detected significant elevation of BDNF (parietal cortex) and NT3 (parietal, temporal and occipital cortex, cingulate gyrus, thalamus, putamen and nucleus caudatus regions) in MDD patients who received antidepressant medication compared to MDD untreated patients and controls. Moreover, we detected a significant decrease of NT3 levels in the parietal cortex of patients suffering from MDD non-treated patients without treatment compared to healthy individuals. Although the limited statistical power due to the small sample size in this proof of concept study corroborates data from previous studies, which show that treatment with antidepressants mediates alterations in neuroplasticity via the action of NTF. However, more research using post-mortem brain tissue with larger samples needs to be carried out as well as longitudinal studies to further verify these results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Collagen degradation as a possibility to determine the post-mortem interval (PMI) of animal bones: a validation study referring to an original study of Boaks et al. (2014).

    Science.gov (United States)

    Jellinghaus, Katharina; Hachmann, Carolin; Hoeland, Katharina; Bohnert, Michael; Wittwer-Backofen, Ursula

    2018-05-01

    Estimation of the post-mortem interval (PMI) of unknown skeletal remains is a common forensic task. Boaks and colleagues demonstrated a new method for PMI estimation in showing a reduction of the collagen to non-collagen content (Co/NCo ratio) in porcine bones after a PMI of 12 months using the Sirius Red/Fast Green Collagen Staining Kit from Chondrex in 2014 (Boaks et al. Forensic Sci Int 240: 104-110, 2014). The aim of our study was to reproduce this method and to investigate if the method could be used for forensic issues. Sixteen fresh porcine bones were placed in prepared boxes where they were treated regularly with distilled water or with water from hay infusions. For determining the Co/NCo ratio, we used the Sirius Red/Fast Green Collagen Staining Kit from Chondrex, which stains collagenous (Co) proteins red and non-collagenous (NCo) proteins green Chondrex Inc. (2008). After a PMI of 1-3 months, an analysis of porcine bone thin sections was performed on the one hand with spectrophotometry, on the other hand with stereomicroscopy. Using spectrophotometry, we go low and partially negative Co/NCo ratios which were up to 100-fold lower than the results we expected to get. The data we got by stereomicroscopy and calculating the Co/NCo ratio from extracting the red and green content with the software MATLAB and so calculating the Co/NCo ratio showed a correlation between PMI and the Co/NCo ratio in the porcine bone samples. Regular addition of distilled water or water from a hay infusion did not produce any significant differences so that an increased presence of microorganisms had obviously no influence on collagen degradation.

  20. Non-pharmacological modification of endothelial function: An important lesson for clinical practice

    Directory of Open Access Journals (Sweden)

    Monika Szulińska

    2018-03-01

    The impact of endothelial function in the complex pathology of cardiovascular diseases reflects a number of scientific proofs showing favorable effects of non-pharmacological interventions in endothelial dysfunction treatment.

  1. Juridical aspects of post mortem adoption

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    Sergio Rodrigo Martinez

    2015-12-01

    Full Text Available The legislature, with the enactment of the Statute of Children and Adolescents, now provides the named posthumous adoption, allowing the death of the adopter, in the course of the procedure does not generate the extinction pleaded adoption. Has the purpose to show that, notwithstanding the absence of such law, the construction of new adopters and adopted by families are recognized, since permeated the socially demonstrated affection, even in passing the death of the person occurs before you have to start legal formalization of the adoption petition, thus characterizing the figure of posthumous adoption without prior judicial manifestation.

  2. Clinical benefit from pharmacological elevation of high-density lipoprotein cholesterol: meta-regression analysis.

    Science.gov (United States)

    Hourcade-Potelleret, F; Laporte, S; Lehnert, V; Delmar, P; Benghozi, Renée; Torriani, U; Koch, R; Mismetti, P

    2015-06-01

    Epidemiological evidence that the risk of coronary heart disease is inversely associated with the level of high-density lipoprotein cholesterol (HDL-C) has motivated several phase III programmes with cholesteryl ester transfer protein (CETP) inhibitors. To assess alternative methods to predict clinical response of CETP inhibitors. Meta-regression analysis on raising HDL-C drugs (statins, fibrates, niacin) in randomised controlled trials. 51 trials in secondary prevention with a total of 167,311 patients for a follow-up >1 year where HDL-C was measured at baseline and during treatment. The meta-regression analysis showed no significant association between change in HDL-C (treatment vs comparator) and log risk ratio (RR) of clinical endpoint (non-fatal myocardial infarction or cardiac death). CETP inhibitors data are consistent with this finding (RR: 1.03; P5-P95: 0.99-1.21). A prespecified sensitivity analysis by drug class suggested that the strength of relationship might differ between pharmacological groups. A significant association for both statins (p<0.02, log RR=-0.169-0.0499*HDL-C change, R(2)=0.21) and niacin (p=0.02, log RR=1.07-0.185*HDL-C change, R(2)=0.61) but not fibrates (p=0.18, log RR=-0.367+0.077*HDL-C change, R(2)=0.40) was shown. However, the association was no longer detectable after adjustment for low-density lipoprotein cholesterol for statins or exclusion of open trials for niacin. Meta-regression suggested that CETP inhibitors might not influence coronary risk. The relation between change in HDL-C level and clinical endpoint may be drug dependent, which limits the use of HDL-C as a surrogate marker of coronary events. Other markers of HDL function may be more relevant. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

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    Almeida A

    2011-08-01

    therapies, while after MDV surgery several patients showed important side effects. Data reinforce that, (1 TN patients should be carefully evaluated before choosing therapy for pain control, (2 different pharmacological approaches are available to initiate pain control at low costs, and (3 criteria for surgical interventions should be clearly defined due to important side effects, with the initial higher costs being strongly reduced with time.Keywords: trigeminal neuralgia, carbamazepine, gabapentin associated with ropivacaine, microvascular decompression, clinical outcomes, direct costs 

  4. A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia

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    Caccia S

    2013-08-01

    Full Text Available Silvio Caccia, Roberto William Invernizzi, Alessandro Nobili, Luca Pasina IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy Abstract: Cariprazine is a potential antipsychotic awaiting approval from the US Food and Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with higher affinity for D3 receptors, as opposed to the D2 antagonism of most older antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive hepatic metabolism by cytochrome P450 (CYP, mainly the highly variable 3A4, with the formation of active metabolites. However, the parent compound – particularly its active didesmethyl derivative – is cleared very slowly, with elimination half-lives in schizophrenic patients ranging from 2–5 days for cariprazine to 2–3 weeks for didesmethyl-cariprazine. Exposure to the latter was several times that for cariprazine, although didesmethyl-cariprazine did not reach steady state within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its therapeutic role comes from press releases and a few abstracts presented at scientific meetings. In short-term controlled trials, it was more effective than placebo in reducing positive and negative symptoms of schizophrenia, with an effective dose range of 1.5–12 mg/day. Although cariprazine was associated with a higher incidence of akathisia and extrapyramidal side effects than placebo, it did not cause weight gain, metabolic abnormalities, prolactin increase, or corrected QT prolongation. Similarly, cariprazine's efficacy and tolerability for the treatment of bipolar disorder (manic/mixed and depressive episodes was established in the dose range of 3–12 mg/day, although again no long-term data are available. Well-designed clinical trials, mainly direct "head-to-head" comparisons with other second-generation antipsychotic agents, are needed to define the therapeutic role and safety profile of cariprazine in schizophrenia and

  5. Bringing stability to the COPD patient: clinical and pharmacological considerations for frequent exacerbators

    Science.gov (United States)

    Gulati, Swati

    2017-01-01

    Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are critical events associated with accelerated loss of lung function, increased morbidity, and excess mortality. AECOPD are heterogeneous in nature and this may directly impact clinical decision making, specifically in patients with frequent exacerbations. A “frequent exacerbator” is a sub-phenotype of COPD that is defined as an individual who experiences ≥2 moderate to severe exacerbations per year. This distinct subgroup has higher mortality and account for more than half of COPD-related hospitalizations annually. Thus, it is imperative to identify individuals at risk for frequent exacerbations and choose optimal strategies to minimize risk for these events. New paradigms for utilizing combination inhalers and the introduction of novel oral compounds provide expanded treatment options to reduce the risk and frequency of exacerbations. The goals of managing frequent exacerbators or patients at risk for AECOPD are: 1) maximizing bronchodilation, 2) reducing inflammation, and 3) targeting specific molecular pathways implicated in COPD and AECOPD pathogenesis. Novel inhaler therapies include combination long acting muscarinic agents (LAMA) plus long acting beta agonists (LABA) show promising results compared to monotherapy or LABA inhaled corticosteroid (ICS) combination in reducing exacerbation risk among individuals at risk for exacerbations and among frequent exacerbators. Likewise, oral medications including macrolides and phosphodiesterase (PDE4) inhibitors reduce the risk for AECOPD in select groups of individuals at high risk for exacerbation. Future direction in COPD management is based on identification of various subtypes or “endotypes” and targeting therapies based on their pathophysiology. This review aims to describe the impact of AECOPD, challenges posed by frequent exacerbators, and explores the rationale for different pharmacologic approaches to preventing AECOPD in these

  6. Pharmacological and clinical dilemmas of prescribing in co-morbid adult attention-deficit/hyperactivity disorder and addiction

    Science.gov (United States)

    Pérez de los Cobos, José; Siñol, Núria; Pérez, Víctor; Trujols, Joan

    2014-01-01

    The present article reviews whether available efficacy and safety data support the pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD) in patients with concurrent substance use disorders (SUD). Arguments for and against treating adult ADHD with active SUD are discussed. Findings from 19 large open studies and controlled clinical trials show that the use of atomoxetine or extended-release methylphenidate formulations, together with psychological therapy, yield promising though inconclusive results about short term efficacy of these drugs in the treatment of adult ADHD in patients with SUD and no other severe mental disorders. However, the efficacy of these drugs is scant or lacking for treating concurrent SUD. No serious safety issues have been associated with these drugs in patients with co-morbid SUD-ADHD, given their low risk of abuse and favourable side effect and drug–drug interaction profile. The decision to treat adult ADHD in the context of active SUD depends on various factors, some directly related to SUD-ADHD co-morbidity (e.g. degree of diagnostic uncertainty for ADHD) and other factors related to the clinical expertise of the medical staff and availability of adequate resources (e.g. the means to monitor compliance with pharmacological treatment). Our recommendation is that clinical decisions be individualized and based on a careful analysis of the advantages and disadvantages of pharmacological treatment for ADHD on a case-by-case basis in the context of active SUD. PMID:23216449

  7. Placas de refratários aluminosos do sistema de válvula gaveta de panelas de aciaria: análise post mortem da degradação química

    Directory of Open Access Journals (Sweden)

    B. B. de Sousa

    Full Text Available Resumo Em uma aciaria, os recipientes que comportam o aço líquido, tais como o forno e a panela de aciaria, são revestidos com materiais refratários especiais para alta temperatura e elevada resistência ao desgaste. O custo desses materiais é alto e, portanto, almeja-se aumentar sua vida útil sem afetar seu desempenho. Este trabalho teve o objetivo de investigar as transformações que ocorrem no material refratário aluminoso de placas de válvula gaveta de panela de aciaria. Para tanto, a região das placas post mortem que entraram em contato com o material líquido a alta temperatura foi caracterizada por meio de análise visual e análises de composição e estrutura através das técnicas de fluorescência de raios X, difração de raios X e análise de microestrutura por microscopia eletrônica de varredura com espectroscopia por dispersão em energia. Como resultado, têm-se contribuições sobre o processo de corrosão química proporcionada pelo contato de escórias residuais com o canal das placas da válvula gaveta. Constatou-se a presença de materiais com alto teor de Ca e compostos por fases como mervinita e guelenita, características de escória, aderidos às placas. Ao mesmo tempo, foi possível estabelecer que a espessura de interação entre o material aderido e a superfície da placa variou entre 0,4 e 1,2 mm. Assim, quando associada à erosão pelo fluxo de aço, a corrosão química decorrente do contato com a escória tem o potencial de intensificar o desgaste da placa refratária.

  8. Interspecies somatic cell nuclear transfer in Asiatic cheetah using nuclei derived from post-mortem frozen tissue in absence of cryo-protectant and in vitro matured domestic cat oocytes.

    Science.gov (United States)

    Moulavi, F; Hosseini, S M; Tanhaie-Vash, N; Ostadhosseini, S; Hosseini, S H; Hajinasrollah, M; Asghari, M H; Gourabi, H; Shahverdi, A; Vosough, A D; Nasr-Esfahani, M H

    2017-03-01

    Recent accomplishments in the field of somatic cell nuclear transfer (SCNT) hold tremendous promise to prevent rapid loss of animal genetic resources using ex situ conservation technology. Most of SCNT studies use viable cells for nuclear transfer into recipient oocytes. However, preparation of live cells in extreme circumstances, in which post-mortem material of endangered/rare animals is improperly retained frozen, is difficult, if not impossible. This study investigated the possibility of interspecies-SCNT (iSCNT) in Asiatic cheetah (Acinonyx jubatus venaticus), a critically endangered subspecies, using nuclei derived from frozen tissue in absence of cryo-protectant at -20 °C and in vitro matured domestic cat oocytes. No cells growth was detected in primary culture of skin and tendon pieces or following culture of singled cells prepared by enzymatic digestion. Furthermore, no live cells were detected following differential viable staining and almost all cells had ruptured membrane. Therefore, direct injection of donor nuclei into enucleated cat oocytes matured in vitro was carried out for SCNT experiments. Early signs of nuclear remodeling were observed as early as 2 h post-iSCNT and significantly increased at 4 h post-iSCNT. The percentages of iSCNT reconstructs that cleaved and developed to 4-16 cell and morula stages were 32.3 ± 7.3, 18.2 ± 9.8 and 5.9 ± 4.3%, respectively. However, none of the iSCNT reconstructs developed to the blastocyst stage. When domestic cat somatic and oocytes were used for control SCNT and parthenogenetic activation, the respective percentages of oocytes that cleaved (51.3 ± 13.9 and 77.3 ± 4.0%) and further developed to the blastocyst stage (11.3 ± 3.3 and 16.8 ± 3.8%) were comparable. In summary, this study demonstrated that enucleated cat oocytes can partially remodel and reactivate non-viable nuclei of Asiatic cheetah and support its reprogramming back to the embryonic stage. To our knowledge, this is

  9. Clinical pharmacology of indomethacin in preterm infants: implications in patent ductus arteriosus closure.

    Science.gov (United States)

    Pacifici, Gian Maria

    2013-10-01

    Indomethacin is a non-steroidal anti-inflammatory drug that is a potent inhibitor of prostaglandin E(2) synthesis. After birth, the ductus arteriosus closes spontaneously within 2-4 days in term infants. The major factor closing the ductus arteriosus is the tension of oxygen, which increases significantly after birth. Prostaglandin E(2) has the opposite effect to that of oxygen; it relaxes smooth muscle and tends to inhibit the closure of the ductus arteriosus. In preterm infants with respiratory distress syndrome, the ductus arteriosus fails to close (patent ductus arteriosus [PDA]) because the concentration of prostaglandin E2 is relatively high. PDA occurs in more than 70 % of neonates weighing less than 1,500 g at birth. The aim of this article was to review the published data on the clinical pharmacology of indomethacin in preterm infants in order to provide a critical analysis of the literature and a useful tool for physicians. The bibliographic search was performed electronically using the PubMed and EMBASE databases as search engines and February 2012 was the cutoff point. A remarkable interindividual variability was observed for the half-life (t(½)), clearance (CL), and volume of distribution (V(d)) of indomethacin. Prophylactic indomethacin consists of a continuous infusion of low levels of indomethacin and may be useful in preterm infants. Extremely preterm infants are less likely to respond to indomethacin. Infants with a postnatal age of 2 months do not respond to treatment with indomethacin. Indomethacin has several adverse effects, the most common of which is renal failure. An increase in serum creatinine of ≥0.5 % mg/dL after indomethacin was observed in about 10-15 % of the patients and creatinine returns to a normal level about 1 week after cessation of therapy. Indomethacin should be administered intravenously by syringe pump for at least 30 min to minimize adverse effects on cerebral, gastrointestinal, and renal blood flow velocities. A

  10. Blended learning for reinforcing dental pharmacology in the clinical years: A qualitative analysis.

    Science.gov (United States)

    Eachempati, Prashanti; Kiran Kumar, K S; Sumanth, K N

    2016-10-01

    Blended learning has become the method of choice in educational institutions because of its systematic integration of traditional classroom teaching and online components. This study aims to analyze student's reflection regarding blended learning in dental pharmacology. A cross-sectional study was conducted in Faculty of Dentistry, Melaka-Manipal Medical College among 3 rd and 4 th year BDS students. A total of 145 dental students, who consented, participate in the study. Students were divided into 14 groups. Nine online sessions followed by nine face-to-face discussions were held. Each session addressed topics related to oral lesions and orofacial pain with pharmacological applications. After each week, students were asked to reflect on blended learning. On completion of 9 weeks, reflections were collected and analyzed. Qualitative analysis was done using thematic analysis model suggested by Braun and Clarke. The four main themes were identified, namely, merits of blended learning, skill in writing prescription for oral diseases, dosages of drugs, and identification of strengths and weakness. In general, the participants had a positive feedback regarding blended learning. Students felt more confident in drug selection and prescription writing. They could recollect the doses better after the online and face-to-face sessions. Most interestingly, the students reflected that they are able to identify their strength and weakness after the blended learning sessions. Blended learning module was successfully implemented for reinforcing dental pharmacology. The results obtained in this study enable us to plan future comparative studies to know the effectiveness of blended learning in dental pharmacology.

  11. Incretin-based therapies– review of the physiology, pharmacology and emerging clinical experience

    DEFF Research Database (Denmark)

    Martin, JH; Deacon, Carolyn F.; Gorrell, MD

    2011-01-01

    in type 2 diabetes, leading to development of strategies aimed at redressing this abnormality. These strategies include pharmacological inhibition of dipeptidyl peptidase-4, the enzyme responsible for the short half-life of endogenous incretins, and administration of long-acting dipeptidyl peptidase-4...

  12. Future clinical trials in DIPG: bringing epigenetics to the clinic

    Directory of Open Access Journals (Sweden)

    Andres E. Morales La Madrid

    2015-07-01

    Full Text Available In spite of major recent advances in DIPG molecular characterization, this body of knowledge has not yet translated into better treatments.To date,more than 250 clinical trials evaluating radiotherapy along with conventional cytotoxic chemotherapy as well as newer biologic agents,have failed to improve the dismal outcome when compared to palliative radiation alone.The biology of DIPG remained unknown until recently when the neurosurgical expertise along with the recognition by the scientific and clinical community of the importance of tissue sampling at diagnosis;ideally in the context of a clinical trial and by trained neurosurgical teams to maximize patient safety.These pre-treatment tumor samples,and others coming from tissue obtained post-mortem,have yielded new insights into DIPG molecular biology.We now know that DIPG comprises a heterogeneous disease with variable molecular phenotypes, different from adult high grade glioma,other non-pontine pediatric high grade gliomas and even between pontine gliomas.The discovery of histone H3.3 or H3.1 mutations has been an important step forward in understanding tumor formation,maintenance and progression.Pharmacologic reversal of DIPG histone demethylation therefore offers an important potential intervention strategy for the treatment of DIPG.To date,clinical trials of newly diagnosed or progressive DIPG with epigenetic modifiers have been unsuccessful.Whether this failure represents limited activity of the agents used,their CNS penetration,redundant pathways within the tumor,or the possibility that histone mutations are necessary only to initiate DIPGs but not maintain their growth,suggest that a great deal still needs to be elucidated in both the underlying biology of these pathways,and the drugs designed to target them.In this review, we discuss the role of both epigenetic and genetic mutations within DIPG and the development of treatment strategies directed against the unique abnormalities

  13. Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study Presença de receptores dopaminérgicos D4 em córtex cerebral humano: um estudo post-mortem

    Directory of Open Access Journals (Sweden)

    Donatella Marazziti

    2007-06-01

    Full Text Available OBJECTIVE: The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [³H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD: Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [³H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM was added to both assays in order to determine the nonspecific binding. RESULTS: Our experiments revealed the presence of specific and saturable binding of [³H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 ± 25 fmol/mg protein, and the dissociation constant was 0.8 ± 0.4 nM. DISCUSSION AND CONCLUSIONS: Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex.OBJETIVO: O objetivo deste estudo foi quantificar a presença e a distribuição de receptores dopaminérgicos do tipo 4 (D4 no córtex cerebral humano em amostras post-mortem através do bloqueio com ³H-YM-09151-2 - um antagonista com afinidade equivalente pelos receptores D2, D3 e D4 - e do desenvolvimento de um método para a detecção específica do componente D4. MÉTODO: Foram obtidas amostras de córtex cerebral de cinco cadáveres. Em um primeiro ensaio, os homogeneizados de tecido cerebral foram incubados em concentrações crescentes de ³H-YM-09151-2, enquanto que o L-745

  14. Treatment of post-partum depression: a review of clinical, psychological and pharmacological options

    Directory of Open Access Journals (Sweden)

    Elizabeth Fitelson

    2010-12-01

    Full Text Available Elizabeth Fitelson1, Sarah Kim4, Allison Scott Baker3, Kristin Leight21Director, 2Attending Psychiatrist, TheWomen's Program, 3Child and Adolescent Psychiatry Fellow, Division of Child Psychiatry, 4PGY-I Resident in Psychiatry, Department of Psychiatry, Columbia University Medical Center, New York, NY, USAAbstract: Postpartum depression (PPD is a common complication of childbearing, and has increasingly been identified as a major public health problem. Untreated maternal depression has multiple potential negative effects on maternal-infant attachment and child development. Screening for depression in the perinatal period is feasible in multiple primary care or obstetric settings, and can help identify depressed mothers earlier. However, there are multiple barriers to appropriate treatment, including concerns about medication effects in breastfeeding infants. This article reviews the literature and recommendations for the treatment of postpartum depression, with a focus on the range of pharmacological, psychotherapeutic, and other non-pharmacologic interventions. Keywords: postpartum depression, postnatal depression, lactation, antidepressant, hormone therapy, psychotherapy, bright light therapy, omega-3

  15. Experimental and Clinical Pharmacology of Andrographis paniculata and Its Major Bioactive Phytoconstituent Andrographolide

    Directory of Open Access Journals (Sweden)

    Thanasekaran Jayakumar

    2013-01-01

    Full Text Available Andrographis paniculata (Burm. F Nees, generally known as “king of bitters,” is an herbaceous plant in the family Acanthaceae. In China, India, Thailand, and Malaysia, this plant has been widely used for treating sore throat, flu, and upper respiratory tract infections. Andrographolide, a major bioactive chemical constituent of the plant, has shown anticancer potential in various investigations. Andrographolide and its derivatives have anti-inflammatory effects in experimental models asthma, stroke, and arthritis. In recent years, pharmaceutical chemists have synthesized numerous andrographolide derivatives, which exhibit essential pharmacological activities such as those that are anti-inflammatory, antibacterial, antitumor, antidiabetic, anti-HIV, antifeedant, and antiviral. However, what is noteworthy about this paper is summarizing the effects of andrographolide against cardiovascular disease, platelet activation, infertility, and NF-κB activation. Therefore, this paper is intended to provide evidence reported in relevant literature on qualitative research to assist scientists in isolating and characterizing bioactive compounds.

  16. Experimental and Clinical Pharmacology of Andrographis paniculata and Its Major Bioactive Phytoconstituent Andrographolide

    Science.gov (United States)

    Jayakumar, Thanasekaran; Hsieh, Cheng-Ying; Lee, Jie-Jen; Sheu, Joen-Rong

    2013-01-01

    Andrographis paniculata (Burm. F) Nees, generally known as “king of bitters,” is an herbaceous plant in the family Acanthaceae. In China, India, Thailand, and Malaysia, this plant has been widely used for treating sore throat, flu, and upper respiratory tract infections. Andrographolide, a major bioactive chemical constituent of the plant, has shown anticancer potential in various investigations. Andrographolide and its derivatives have anti-inflammatory effects in experimental models asthma, stroke, and arthritis. In recent years, pharmaceutical chemists have synthesized numerous andrographolide derivatives, which exhibit essential pharmacological activities such as those that are anti-inflammatory, antibacterial, antitumor, antidiabetic, anti-HIV, antifeedant, and antiviral. However, what is noteworthy about this paper is summarizing the effects of andrographolide against cardiovascular disease, platelet activation, infertility, and NF-κB activation. Therefore, this paper is intended to provide evidence reported in relevant literature on qualitative research to assist scientists in isolating and characterizing bioactive compounds. PMID:23634174

  17. A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia

    Directory of Open Access Journals (Sweden)

    Kim Lawson

    2017-05-01

    Full Text Available Fibromyalgia is a complex chronic condition characterized by pain, physical fatigue, sleep disorder and cognitive impairment. Evidence-based guidelines recommend antidepressants as treatments of fibromyalgia where tricyclics are often considered to have the greatest efficacy, with amitriptyline often being a first-line treatment. Amitriptyline evokes a preferential reduction in pain and fatigue of fibromyalgia, and in the Fibromyalgia Impact Questionnaire (FIQ score, which is a quality of life assessment. The multimodal profile of the mechanisms of action of amitriptyline include monoamine reuptake inhibition, receptor modulation and ion channel modulation. Several of the actions of amitriptyline on multiple nociceptive and sensory processes at central and peripheral locations have the potential to act cumulatively to suppress the characteristic symptoms of fibromyalgia. Greater understanding of the role of these mechanisms of action of amitriptyline could provide further clues to the pathophysiology of fibromyalgia and to a preferable pharmacological profile for future drug development.

  18. A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia

    Science.gov (United States)

    Lawson, Kim

    2017-01-01

    Fibromyalgia is a complex chronic condition characterized by pain, physical fatigue, sleep disorder and cognitive impairment. Evidence-based guidelines recommend antidepressants as treatments of fibromyalgia where tricyclics are often considered to have the greatest efficacy, with amitriptyline often being a first-line treatment. Amitriptyline evokes a preferential reduction in pain and fatigue of fibromyalgia, and in the Fibromyalgia Impact Questionnaire (FIQ) score, which is a quality of life assessment. The multimodal profile of the mechanisms of action of amitriptyline include monoamine reuptake inhibition, receptor modulation and ion channel modulation. Several of the actions of amitriptyline on multiple nociceptive and sensory processes at central and peripheral locations have the potential to act cumulatively to suppress the characteristic symptoms of fibromyalgia. Greater understanding of the role of these mechanisms of action of amitriptyline could provide further clues to the pathophysiology of fibromyalgia and to a preferable pharmacological profile for future drug development. PMID:28536367

  19. Trace Amines and the Trace Amine-Associated Receptor 1: Pharmacology, Neurochemistry and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Yue ePei

    2016-04-01

    Full Text Available Biogenic amines are a collection of endogenous molecules that play pivotal roles as neurotransmitters and hormones. In addition to the classical biogenic amines resulting from decarboxylation of aromatic acids, including dopamine (DA, norepinephrine, epinephrine, serotonin (5-HT and histamine, other biogenic amines, present at much lower concentrations in the central nervous system (CNS, and hence referred to as trace amines (TAs, are now recognized to play significant neurophysiological and behavioural functions. At the turn of the century, the discovery of the trace amine-associated receptor 1 (TAAR1, a phylogenetically conserved G protein-coupled receptor that is responsive to both TAs, such as β-phenylethylamine, octopamine and tyramine, and structurally-related amphetamines, unveiled mechanisms of action for TAs other than interference with aminergic pathways, laying the foundations for deciphering the functional significance of TAs and its mammalian CNS receptor, TAAR1. Although its molecular interactions and downstream targets have not been fully elucidated, TAAR1 activation triggers accumulation of intracellular cAMP, modulates PKA and PKC signalling and interferes with the β-arrestin2-dependent pathway via G protein-independent mechanisms. TAAR1 is uniquely positioned to exert direct control over DA and 5-HT neuronal firing and release, which has profound implications for understanding the pathophysiology of, and therefore designing more efficacious therapeutic interventions for, a range of neuropsychiatric disorders that involve aminergic dysregulation, including Parkinson’s disease, schizophrenia, mood disorders and addiction. Indeed, the recent development of novel pharmacological tools targeting TAAR1 has uncovered the remarkable potential of TAAR1-based medications as new generation pharmacotherapies in neuropsychiatry. This review summarizes recent developments in the study of TAs and TAAR1, their intricate neurochemistry and

  20. Evaluation of a filmed clinical scenario as a teaching resource for an introductory pharmacology unit for undergraduate health students: A pilot study.

    Science.gov (United States)

    East, Leah; Hutchinson, Marie

    2015-12-01

    Simulation is frequently being used as a learning and teaching resource for both undergraduate and postgraduate students, however reporting of the effectiveness of simulation particularly within the pharmacology context is scant. The aim of this pilot study was to evaluate a filmed simulated pharmacological clinical scenario as a teaching resource in an undergraduate pharmacological unit. Pilot cross-sectional quantitative survey. An Australian university. 32 undergraduate students completing a healthcare degree including nursing, midwifery, clinical science, health science, naturopathy, and osteopathy. As a part of an undergraduate online pharmacology unit, students were required to watch a filmed simulated pharmacological clinical scenario. To evaluate student learning, a measurement instrument developed from Bloom's cognitive domains (knowledge, comprehension, application, analysis, synthesis and evaluation) was employed to assess pharmacological knowledge conceptualisation and knowledge application within the following fields: medication errors; medication adverse effects; medication interactions; and, general pharmacology. The majority of participants were enrolled in an undergraduate nursing or midwifery programme (72%). Results demonstrated that the majority of nursing and midwifery students (56.52%) found the teaching resource complementary or more useful compared to a lecture although less so compared to a tutorial. Students' self-assessment of learning according to Bloom's cognitive domains indicated that the filmed scenario was a valuable learning tool. Analysis of variance indicated that health science students reported higher levels of learning compared to midwifery and nursing. Students' self-report of the learning benefits of a filmed simulated clinical scenario as a teaching resource suggest enhanced critical thinking skills and knowledge conceptualisation regarding pharmacology, in addition to being useful and complementary to other teaching and

  1. FDG PET in non-pharmacological therapy in Alzheimer's disease; cerebral metabolic increase correlates with clinical improvement after cognitive therapy

    International Nuclear Information System (INIS)

    Na, Hae Ri; Kim, Yu Kyeong; Park, Seong Min; Lee, Seung Hyun; Park, Eun Kyung; Lee, Jung Seok; Kim, Sang Yun; Kim, Sang Eun

    2007-01-01

    In management of AD, pharmacological treatment alone using acetylcholinesterase inhibitor (AChEI) is general consensus, and provides beneficial effect to prolong their progression. Combined non-pharmacological therapy, especially cognitive therapy is recently having attention with expectation of improvement in cognitive ability. This study examined the effect of combined cognitive therapy in AD patients who were maintaining AChEI using FDG PET. Four patients (689 yrs) who diagnosed as probable Alzheimer's disease based on the NINCDS-ADRDA criteria participated in this study. 12-week cognitive therapy comprised seven fields to enhance orientation, memory, recall, visuo-motor organization, categorization and behavior modification/sequencing. They received 45-minute sessions twice per week with maintaining their previous medication. Clinical improvement was assessed by comprehensive neuropsychological tests. Two FDG PET studies were performed before cognitive therapy and in the middle of the therapy, and compared to evaluate the effect of cognitive therapy to cerebral metabolism. Two of 4 patients whose initial cognitive impairment was milder had clinical improvement after 12 weeks, the rest who were more severely impaired failed to have clinical improvement. Regional cerebral hypometabolism on initial PET was correlated with their functional status. Follow up PET of two responders demonstrated the increases in regional metabolism in the temporal and/or frontal cortex, which was associated their functional improvement. Cerebral metabolism in poor responders were minimally increased or no changed. This preliminary data suggests that cognitive therapy is potentially useful to stabilize or improve cognitive and functional performance in AD patients with relatively mild cognitive dysfunction. And FDG PET could demonstrate possible candidates for cognitive therapy and the effect of the therapy

  2. A feasibility study of a new approach to clinical radiosensitisation: hypothermia and hyperbaric oxygen in combination with pharmacological vasodilatation

    International Nuclear Information System (INIS)

    Sealy, R.; Harrison, G.G.; Morrell, D.; Cape Town Univ.

    1986-01-01

    It is proposed that hyperbaric oxygen fails in the clinical situation due to a high proportion (greater than 33%) of hypoxic cells in human tumours. The means of overcoming this problem are reviewed. Additional to hyperbaric oxygenation, moderate hypothermia (30 0 C) to allow redistribution of oxygen in the tumour is proposed. A system of externally controlled intravenous anaesthesia has been developed for the single-subject hypervaric cylinder. Pharmacological vasodilatation is induced in the anaesthetised patient who is then fluid loaded and cooled. Initial single-sensitising treatments are advocated. Twenty-nine patients with advanced mouth cancer have completed a course of this treatment, of whom five of nine were free of disease after 2 years and 10 of 21 at 1 year, with three intercurrent deaths. Fifteen have experienced local failure. This approach would appear to be practical, safe and promising. (author)

  3. Prescribing knowledge in the light of undergraduate clinical pharmacology and therapeutics teaching in India: views of first-year postgraduate students

    Directory of Open Access Journals (Sweden)

    Upadhyaya P

    2012-06-01

    Full Text Available Prerna Upadhyaya,1 Vikas Seth,2 Monika Sharma,1 Mushtaq Ahmed,1 Vijay Vasant Moghe,1 Zafar Yab Khan,1 Vinay Kumar Gupta,1 Shipra Vikram Jain,1 Utkarsh Soni,1 Manohar Bhatia,1 Kumar Abhijit,1 Jaswant Goyal11Department of Pharmacology, Mahatma Gandhi Medical College, Jaipur, 2Department of Pharmacology, Hind Institute of Medical Sciences, Lucknow, IndiaObjectives: The study aimed to review the prescribing knowledge of first-year postgraduate doctors in a medical college in India, using the principles of good prescribing, to suggest strategies to improve rational prescribing, and to recommend what curriculum planners can do to accomplish this objective.Methods: Fifty first-year postgraduate doctors were asked to fill in a structured questionnaire that sought information regarding their undergraduate training in clinical pharmacology and therapeutics, prescribing habits, and commonly consulted drug information sources. Also, the questionnaire assessed any perceived deficiencies in their undergraduate clinical pharmacology teaching and sought feedback regarding improvement in the teaching.Results: Eighty-eight percent of residents said that they were taught prescription writing in undergraduate pharmacology teaching; 48% of residents rated their prescribing knowledge at graduation as average, 28% good, 4% excellent, 14% poor, and 4% very poor; 58% felt that their undergraduate training did not prepare them to prescribe safely, and 62% felt that their training did not prepare them to prescribe rationally. Fifty-eight percent of residents felt that they had some specific problems with writing a prescription during their internship training, while 92% thought that undergraduate teaching should be improved. Their suggestions for improving teaching methods were recorded.Conclusions: This study concludes that efforts are needed to develop a curriculum that encompasses important aspects of clinical pharmacology and therapeutics along with incorporation of

  4. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Jain S

    2017-03-01

    Full Text Available Sachin Jain,1 Ruolan Song,2 Jingwu Xie2 1Indiana University School of Medicine, 2Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indianapolis, IN, USA Abstract: The Hedgehog (Hh pathway is critical for cell differentiation, tissue polarity, and stem cell maintenance during embryonic development, but is silent in adult tissues under normal conditions. However, aberrant Hh signaling activation has been implicated in the development and promotion of certain types of cancer, including basal cell carcinoma (BCC, medulloblastoma, and gastrointestinal cancers. In 2015, the US Food and Drug Administration (FDA approved sonidegib, a smoothened (SMO antagonist, for treatment of advanced BCC (aBCC after a successful Phase II clinical trial. Sonidegib, also named Odomzo, is the second Hh signaling inhibitor approved by the FDA to treat BCCs following approval of the first SMO antagonist vismodegib in 2012. What are the major features of sonidegib (mechanism of action; metabolic profiles, clinical efficacy, safety, and tolerability profiles? Will the sonidegib experience help other clinical trials using Hh signaling inhibitors in the future? In this review, we will summarize current understanding of BCCs and Hh signaling. We will focus on sonidegib and its use in the clinic, and we will discuss ways to improve its clinical application in cancer therapeutics. Keywords: Hedgehog, smoothened, inhibitor, cancer, basal cell carcinoma, sonidegib

  5. [Clinical and pharmacological aspects of rifaximin, local antibiotic therapy in intestinal disorders].

    Science.gov (United States)

    Gasztonyi, Beáta; Hunyady, Béla

    2004-10-24

    The authors report pharmacokinetics and indications of rifaximin and the results of clinical studies. Rifaximin has a large antibacterial spectrum with a good therapeutic effect on both gram positive and gram negative aerob and anaerob bacteria. Practically there is no absorption (< 1%) following oral administration with a high concentration in gastrointestinal mucosa (8000 microg/g). No increase in absorption can be detected in intestinal damage caused by inflammatory bowel disease. The remarkable safety profile of rifaximin is due to its negligible quality of absorption. According to the clinical studies rifaximin could be an adequate therapeutic approach in all gastrointestinal diseases and interventions when antibacterial therapy is needed.

  6. Systematic review of clinical trials assessing pharmacological properties of Salvia species on memory, cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Miroddi, Marco; Navarra, Michele; Quattropani, Maria C; Calapai, Fabrizio; Gangemi, Sebastiano; Calapai, Gioacchino

    2014-06-01

    Salvia officinalis L. and Salvia lavandulaefolia L. have a longstanding use as traditional herbal remedies that can enhance memory and improve cognitive functions. Pharmacological actions of S. officinalis and S. lavandulaefolia on healthy subjects and on patients suffering of cognitive decline have been investigated. Aim of this review was to summarize published clinical trials assessing effectiveness and safety of S. officinalis and S. lavandulaefolia in the enhancement of cognitive performance in healthy subjects and neurodegenerative illnesses. Furthermore, to purchase a more complete view on safety of S. officinalis and S. lavandulaefolia, we collected and discussed articles regarding toxicity and adverse reactions. Eight clinical studies investigating on acute effects of S. officinalis on healthy subjects were included in the review. Six studies investigated on the effects of S. officinalis and S. lavandaeluaefolia on cognitive performance in healthy subjects. The two remaining were carried out to study the effects of sage on Azheimer's disease. Our review shows that S. officinalis and S. lavandulaefolia exert beneficial effects by enhancing cognitive performance both in healthy subjects and patients with dementia or cognitive impairment and is safe for this indication. Unfortunately, promising beneficial effects are debased by methodological issues, use of different herbal preparations (extracts, essential oil, use of raw material), lack of details on herbal products used. We believe that sage promising effects need further higher methodological standard clinical trials. © 2014 John Wiley & Sons Ltd.

  7. Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders

    Directory of Open Access Journals (Sweden)

    Jost WH

    2015-04-01

    Full Text Available Wolfgang H Jost,1 Reiner Benecke,2 Dieter Hauschke,3 Joseph Jankovic,4 Petr Kaňovský,5 Peter Roggenkämper,6 David M Simpson,7 Cynthia L Comella81Department of Neurology, University of Freiburg, Freiburg, Germany; 2Clinic and Policlinic for Neurology, University of Rostock, Rostock, Germany; 3Institute of Medical Biometry and Medical Informatics, University of Freiburg, Freiburg, Germany; 4Department of Neurology, Baylor College of Medicine, Houston, TX, USA; 5Department of Neurology, Palacky University Olomouc, Faculty of Medicine and Dentistry and University Hospital, Olomouc, Czech Republic; 6University Eye Clinic of Bonn, Bonn, Germany; 7Icahn School of Medicine at Mount Sinai, New York, NY, USA; 8Rush University Medical Center, Chicago, IL, USABackground: IncobotulinumtoxinA (Xeomin® is a purified botulinum neurotoxin type A formulation, free from complexing proteins, with proven efficacy and good tolerability for the treatment of neurological conditions such as blepharospasm, cervical dystonia (CD, and post-stroke spasticity of the upper limb. This article provides a comprehensive overview of incobotulinumtoxinA based on randomized controlled trials and prospective clinical studies.Summary: IncobotulinumtoxinA provides clinical efficacy in treating blepharospasm, CD, and upper-limb post-stroke spasticity based on randomized, double-blind, placebo-controlled trials with open-label extension periods (total study duration up to 89 weeks. Adverse events were generally mild or moderate. The most frequent adverse events, probably related to the injections, included eyelid ptosis and dry eye in the treatment of blepharospasm, dysphagia, neck pain, and muscular weakness in patients with CD, and injection site pain and muscular weakness when used for treating spasticity. In blepharospasm and CD, incobotulinumtoxinA was investigated in clinical trials permitting flexible intertreatment intervals based on the individual patient’s clinical need

  8. Thuja occidentalis (Arbor vitae): A Review of its Pharmaceutical, Pharmacological and Clinical Properties

    OpenAIRE

    Naser, Belal; Bodinet, Cornelia; Tegtmeier, Martin; Lindequist, Ulrike

    2005-01-01

    Arbor vitae (Thuja occidentalis L.) is a native European tree widely used in homeopathy and evidence-based phytotherapy. Many reviews and monographs have been published on the herbal substance's description, mode of action and clinical use. However, no comprehensive evidence-based review is available. Therefore, our aim was to search MEDLINE databases and survey manufacturers for further details or unpublished data. This review presents the botany, ethnobotany and phytochemistry, especial...

  9. Thuja occidentalis (Arbor vitae: A Review of its Pharmaceutical, Pharmacological and Clinical Properties

    Directory of Open Access Journals (Sweden)

    Belal Naser

    2005-01-01

    Full Text Available Arbor vitae (Thuja occidentalis L. is a native European tree widely used in homeopathy and evidence-based phytotherapy. Many reviews and monographs have been published on the herbal substance's description, mode of action and clinical use. However, no comprehensive evidence-based review is available. Therefore, our aim was to search MEDLINE databases and survey manufacturers for further details or unpublished data. This review presents the botany, ethnobotany and phytochemistry, especially the different contents of essential oil (Thujone in relation to different extraction procedures of this medicinal plant. Thuja's antiviral action and immunopharmacological potential, such as stimulatory and co-stimulatory effects on cytokine and antibody production and activation of macrophages and other immunocompetent cells, have been evaluated in numerous in vitro and in vivo investigations. Although no controlled trials have been conducted on Thuja occ alone, many clinical studies have been performed with a herbal medicinal product containing a special extract of Thuja occ and other immunostimulants, demonstrating its therapeutic efficacy and safety in respiratory tract infections.

  10. Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 1: Regulatory Context and Risk Management.

    Science.gov (United States)

    Sellers, Edward M

    2018-02-01

    This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance. The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk. The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system-active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development. If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.

  11. Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

    Directory of Open Access Journals (Sweden)

    Davis-Ajami ML

    2014-04-01

    Full Text Available Mary Lynn Davis-Ajami,1 Jun Wu,2 Katherine Downton,3 Emilie Ludeman,3 Virginia Noxon4 1Organizational Systems and Adult Health, University of Maryland School of Nursing, Baltimore, MD, USA; 2South Carolina College of Pharmacy, University of South Carolina, Greenville, SC, USA; 3Health Sciences and Human Services Library, University of Maryland, Baltimore, MD, USA; 4Department of Clinical Pharmacy and Outcomes Science, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC, USA Abstract: Epoetin zeta was granted marketing authorization in October 2007 by the European Medicines Agency as a recombinant human erythropoietin erythropoiesis-stimulating agent to treat symptomatic anemia of renal origin in adult and pediatric patients on hemodialysis and adults on peritoneal dialysis, as well as for symptomatic renal anemia in adult patients with renal insufficiency not yet on dialysis. Currently, epoetin zeta can be administered either subcutaneously or intravenously to correct for hemoglobin concentrations ≤10 g/dL (6.2 mmol/L or with dose adjustment to maintain hemoglobin levels at desired levels not in excess of 12 g/dL (7.5 mmol/L. This review article focuses on epoetin zeta indications in chronic kidney disease, its use in managing anemia of renal origin, and discusses its pharmacology and clinical utility. Keywords: biosimilar, chronic kidney disease, epoetin alfa, erythropoiesis, renal anemia, Retacrit®

  12. Trends in qualifying biomarkers in drug safety. Consensus of the 2011 meeting of the spanish society of clinical pharmacology.

    Science.gov (United States)

    Agúndez, José A G; Del Barrio, Jaime; Padró, Teresa; Stephens, Camilla; Farré, Magí; Andrade, Raúl J; Badimon, Lina; García-Martín, Elena; Vilahur, Gemma; Lucena, M Isabel

    2012-01-01

    In this paper we discuss the consensus view on the use of qualifying biomarkers in drug safety, raised within the frame of the XXIV meeting of the Spanish Society of Clinical Pharmacology held in Málaga (Spain) in October, 2011. The widespread use of biomarkers as surrogate endpoints is a goal that scientists have long been pursuing. Thirty years ago, when molecular pharmacogenomics evolved, we anticipated that these genetic biomarkers would soon obviate the routine use of drug therapies in a way that patients should adapt to the therapy rather than the opposite. This expected revolution in routine clinical practice never took place as quickly nor with the intensity as initially expected. The concerted action of operating multicenter networks holds great promise for future studies to identify biomarkers related to drug toxicity and to provide better insight into the underlying pathogenesis. Today some pharmacogenomic advances are already widely accepted, but pharmacogenomics still needs further development to elaborate more precise algorithms and many barriers to implementing individualized medicine exist. We briefly discuss our view about these barriers and we provide suggestions and areas of focus to advance in the field.

  13. Clinical evaluation of a nutraceutical diet as an adjuvant to pharmacological treatment in dogs affected by Keratoconjunctivitis sicca.

    Science.gov (United States)

    Destefanis, Simona; Giretto, Daniela; Muscolo, Maria Cristina; Di Cerbo, Alessandro; Guidetti, Gianandrea; Canello, Sergio; Giovazzino, Angela; Centenaro, Sara; Terrazzano, Giuseppe

    2016-09-22

    Canine keratoconjunctivitis sicca (cKCS) is an inflammatory eye condition related to a deficiency in the tear aqueous fraction. Etiopathogenesis of such disease is substantially multifactorial, combining the individual genetic background with environmental factors that contribute to the process of immunological tolerance disruption and, as a consequence, to the emergence of autoimmunity disease. In this occurrence, it is of relevance the role of the physiological immune-dysregulation that results in immune-mediated processes at the basis of cKCS. Current therapies for this ocular disease rely on immunosuppressive treatments. Clinical response to treatment frequently varies from poor to good, depending on the clinical-pathological status of eyes at diagnosis and on individual response to therapy. In the light of the variability of clinical response to therapies, we evaluated the use of an anti-inflammatory/antioxidant nutraceutical diet with potential immune-modulating activity as a therapeutical adjuvant in cKCS pharmacological treatment. Such combination was administered to a cohort of dogs affected by cKCS in which the only immunosuppressive treatment resulted poorly responsive or ineffective in controlling the ocular symptoms. Fifty dogs of different breeds affected by immune-mediated cKCS were equally distributed and randomly assigned to receive either a standard diet (control, n = 25) or the nutraceutical diet (treatment group, n = 25) both combined with standard immunosuppressive therapy over a 60 days period. An overall significant improvement of all clinical parameters (tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge) and the lack of food-related adverse reactions were observed in the treatment group (p metabolic changes could affect the immune response orchestration in a model of immune-mediated ocular disease, as represented by cKCS.

  14. Educational Paper: Aspects of clinical pharmacology in children--pharmacovigilance and safety.

    Science.gov (United States)

    Choonara, Imti

    2013-05-01

    Adverse drug reactions (ADRs) are a significant problem in children, affecting one in ten children in hospital. Within the community, one in 500 children will experience an adverse drug reaction each year. Pharmacovigilance has been useful in detecting suspected ADRs. However, most ADRs are unreported and often not suspected. Education of health professionals in relation to drug toxicity improves the reporting rate of suspected ADRs. Clinical trials are useful to evaluate the efficacy of drugs. They are, however, not the best way of looking at ADRs where surveillance following the widespread use of a drug is more appropriate. Alongside work by the regulatory agencies, independent investigators have helped collate data. This information has been useful in developing guidelines to prevent further cases of drug toxicity. Greater awareness and understanding of drug toxicity in children should result in more rational prescribing.

  15. [Pharmacology of local anesthetics and clinical aspects of segmental blocking. II. Spinal anesthesia].

    Science.gov (United States)

    Kozlov, S P; Svetlov, V A; Luk'ianov, M V

    1998-01-01

    Clinical picture of development of segmental blocking after subarachnoidal injection of hyperbaric solutions of 0.75% bupivacaine, 5% ultracaine, and isobaric 0.5% bupivacaine is studied. A total of 152 patients operated on the lower part of the body and the lower limbs were examined under conditions of single, prolonged subarachnoidal, and combined spinal epidural anesthesia. Ultracaine and bupivacaine in different concentrations with different barism provided anesthesia equivalent by the efficacy, depth, and dissemination of sensory block. Segmental blocking with 5% ultracaine was characterized by the shortest latent period (3.14 +/- 0.16 min, p anesthesia in comparison with a single injection, and combined spinal epidural anesthesia shortened the latent period of segmental blocking and ensured intraoperative anesthesia and postoperative analgesia at the expense of the epidural component.

  16. Verapamil for cluster headache. Clinical pharmacology and possible mode of action

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Tfelt-Hansen, Jacob

    2009-01-01

    is therefore limited. The clinical use of verapamil in cluster headache is reviewed and several relevant drug interactions are mentioned. Finally, its possible mode of action in cluster headache is discussed. The effect of verapamil in cluster headache most likely takes place in the hypothalamus......Verapamil is used mainly in cardiovascular diseases. High-dose verapamil (360-720 mg) is, however, currently the mainstay in the prophylactic treatment of cluster headache. The oral pharmacokinetics are variable. The pharmacodynamic effect of verapamil, the effect on blood pressure, also varies.......Verapamil is an L-type calcium channel blocker but it is also a blocker of other calcium channels (T-, P-, and possibly N- and Q-type Ca(2+) channels) and the human ether-a-go-go-related gene potassium channel. With so many different actions of verapamil, it is impossible at the present time to single out a certain...

  17. CLINICAL AND PHARMACOLOGICAL APPROACHES TO OPTIMIZE THE DOSING REGIMEN OF ANTIBACTERIAL DRUGS IN PEDIATRICS

    Directory of Open Access Journals (Sweden)

    Natal’ya B. Lazareva

    2018-01-01

    Full Text Available The rational use of antibacterial drugs in children implies an adequate choice of the necessary medication, its dosing regimen, and the duration of treatment in order to achieve maximum efficacy and minimize toxic effects. The knowledge of pharmacokinetic and pharmacodynamic profiles of the antibacterial drug plays a crucial role for optimizing the dosing regimen. The strategy of individual choice of the dosing regimen, taking into account the principles of pharmacokinetics and pharmacodynamics, can be especially effective in patients with the expectedly changed parameters of pharmacokinetics and in infections caused by bacteria strains with low sensitivity to antibiotics. The review presents a contemporary view of pharmacokinetic and pharmacodynamic profiles of antibacterial drugs most commonly used in pediatrics and their relationship to the clinical efficacy of the administered therapy.

  18. Genetic, clinical and pharmacological determinants of out-of-hospital cardiac arrest : rationale and outline of the AmsteRdam Resuscitation Studies (ARREST) registry

    NARCIS (Netherlands)

    Blom, M T; van Hoeijen, D A; Bardai, A; Berdowski, J; Souverein, P C; De Bruin, M L; Koster, R W; de Boer, A; Tan, H L

    2014-01-01

    INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a major public health problem. Recognising the complexity of the underlying causes of OHCA in the community, we aimed to establish the clinical, pharmacological, environmental and genetic factors and their interactions that may cause OHCA.

  19. Treatment outcomes of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis in daily clinical practice.

    NARCIS (Netherlands)

    Snijders, G.F.; Ende, C.H.M. van den; Bemt, B.J.F van den; Riel, P.L.C.M. van; Hoogen, F.H.J. van den; Broeder, A. den

    2012-01-01

    OBJECTIVES: To describe the results of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis (OA) in daily clinical practice. METHODS: In this observational cohort study, standardised conservative treatment was offered to patients

  20. Recent developments in the clinical pharmacology of rolapitant: subanalyses in specific populations

    Directory of Open Access Journals (Sweden)

    Rapoport BL

    2017-09-01

    Full Text Available Bernardo Leon Rapoport,1 Matti Aapro,2 Martin R Chasen,3 Karin Jordan,4 Rudolph M Navari,5 Ian Schnadig,6 Lee Schwartzberg7 1The Medical Oncology Centre of Rosebank, Johannesburg, South Africa; 2Breast Center, Genolier Cancer Center, Genolier, Switzerland; 3Palliative Care, William Osler Health Services, Brampton, ON, Canada; 4Department of Medicine V, University of Heidelberg, Heidelberg, Germany; 5Division of Hematology Oncology, University of Alabama School of Medicine, Birmingham, AL, USA; 6Compass Oncology, US Oncology Research, Tualatin, OR, USA; 7West Clinic, Memphis, TN, USA Abstract: Knowledge of the involvement of the neurokinin substance P in emesis has led to the development of the neurokinin-1 receptor antagonists (NK-1 RAs for control of chemotherapy-induced nausea and vomiting (CINV, in combination with serotonin type 3 receptor antagonists and corticosteroids. The NK-1 RA rolapitant, recently approved in oral formulation, has nanomolar affinity for the NK-1 receptor, as do the other commercially available NK-1 RAs, aprepitant and netupitant. Rolapitant is rapidly absorbed and has a long half-life in comparison to aprepitant and netupitant. All three NK-1 RAs undergo metabolism by cytochrome P450 (CYP 3A4, necessitating caution with the concomitant use of CYP3A4 inhibitors, but in contrast to aprepitant and netupitant, rolapitant does not inhibit or induce CYP3A4. However, rolapitant is a moderate inhibitor of CYP2D6, and concomitant use with CYP2D6 substrates with narrow therapeutic indices should be avoided. Aprepitant, netupitant, and rolapitant have all demonstrated efficacy in the control of delayed CINV in patients receiving moderately and highly emetogenic chemotherapy in randomized controlled trials, including over multiple cycles of chemotherapy. We reviewed recent post hoc analyses of clinical trial data demonstrating that rolapitant is efficacious in the control of CINV in patient populations with specific tumor types

  1. Behavioral and pharmacological treatment methods for pregnant smokers: issues for clinical practice.

    Science.gov (United States)

    Windsor, R; Oncken, C; Henningfield, J; Hartmann, K; Edwards, N

    2000-01-01

    Active and passive exposure to tobacco smoke are the most serious and preventable causes of poor maternal, fetal, and infant outcomes in the United States. Unfortunately, the majority of pregnant smokers do not quit smoking before or during pregnancy or after childbirth. We describe a standardized behavioral counseling model and discuss issues to consider in recommending the use of pharmacotherapy during pregnancy. Although the Food and Drug Administration no longer classifies nicotine replacement therapy (NRT) as contraindicated during pregnancy, precautions should be carefully considered for use in this population. This paper provides a synopsis of the risks of exposure to tobacco smoke during pregnancy and the postpartum; estimates the population at risk and the potential for increased cessation if effective health education methods during pregnancy were routinely provided; presents a meta-analysis of "best practice" patient education methods for pregnant smokers; and estimates the number of pregnant heavy smokers who might be eligible for NRT. We suggest five issues for the physician to consider before recommending NRT medications to pregnant patients who are heavy smokers. The judicious use of NRT medications may significantly reduce harm to the infants of heavy smokers. More evidence derived from large population-based research, however, is needed to provide guidance to the physician about NRT eligibility, dose, scheduling, and effectiveness in clinical practice.

  2. Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists.

    Science.gov (United States)

    Aghazadeh Tabrizi, Mojgan; Baraldi, Pier Giovanni; Baraldi, Stefania; Gessi, Stefania; Merighi, Stefania; Borea, Pier Andrea

    2017-07-01

    Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed on sensory neurons triggering an influx of cations. TRPV1 receptors function as homotetramers responsive to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Its phosphorylation increases sensitivity to both chemical and thermal stimuli, while desensitization involves a calcium-dependent mechanism resulting in receptor dephosphorylation. TRPV1 functions as a sensor of noxious stimuli and may represent a target to avoid pain and injury. TRPV1 activation has been associated to chronic inflammatory pain and peripheral neuropathy. Its expression is also detected in nonneuronal areas such as bladder, lungs, and cochlea where TRPV1 activation is responsible for pathology development of cystitis, asthma, and hearing loss. This review offers a comprehensive overview about TRPV1 receptor in the pathophysiology of chronic pain, epilepsy, cough, bladder disorders, diabetes, obesity, and hearing loss, highlighting how drug development targeting this channel could have a clinical therapeutic potential. Furthermore, it summarizes the advances of medicinal chemistry research leading to the identification of highly selective TRPV1 antagonists and their analysis of structure-activity relationships (SARs) focusing on new strategies to target this channel. © 2016 Wiley Periodicals, Inc.

  3. Clinical pharmacology of sibutramine hydrochloride (BTS 54524), a new antidepressant, in healthy volunteers.

    Science.gov (United States)

    King, D J; Devaney, N

    1988-01-01

    The cardiovascular, anticholinergic and central effects of single doses of 30, 45 and 60 mg of sibutramine hydrochloride (BTS 54524), a new potential antidepressant, were compared with amitriptyline (50 mg) and placebo given at weekly intervals in a randomised design to six healthy male volunteers. Sibutramine was associated with increases in both supine heart rate and systolic blood pressure at 1, 2 and 6 h after 60 mg (P less than 0.05). Amitriptyline caused a significant 50-60% decrease in salivation compared with placebo at 2 and 6 h but there were no changes with sibutramine. No significant changes in pupil size were detected with either drug. Visual analogue rating scales (VARS) revealed significant drowsiness with amitriptyline but neither sedative nor stimulant effects with sibutramine. Impairments of simple auditory and visual reaction times, visual two-choice reaction time, finger tapping and trail making, measured using an automated test battery, occurred with amitriptyline compared with sibutramine. If sibutramine proves to be an effective antidepressant it should be devoid of anticholinergic or central depressant effects. Chronic dosage studies are indicated to evaluate the clinical significance of its cardiovascular effects. PMID:3207566

  4. Delafloxacin: Place in Therapy and Review of Microbiologic, Clinical and Pharmacologic Properties.

    Science.gov (United States)

    Jorgensen, Sarah C J; Mercuro, Nicholas J; Davis, Susan L; Rybak, Michael J

    2018-03-31

    Delafloxacin (formerly WQ-3034, ABT492, RX-3341) is a novel fluoroquinolone chemically distinct from currently marketed fluoroquinolones with the absence of a protonatable substituent conferring a weakly acidic character to the molecule. This property results in increased intracellular penetration and enhanced bactericidal activity under acidic conditions that characterize the infectious milieu at a number of sites. The enhanced potency and penetration in low pH environments contrast what has been observed for other zwitterionic fluoroquinolones, which tend to lose antibacterial potency under acidic conditions, and may be particularly advantageous against methicillin-resistant Staphylococcus aureus, for which the significance of the intracellular mode of survival is increasingly being recognized. Delafloxacin is also unique in its balanced target enzyme inhibition, a property that likely explains the very low frequencies of spontaneous mutations in vitro. Delafloxacin recently received US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections and is currently being evaluated in a phase 3 trial among patients with community-acquired pneumonia. In the current era of a heightened awareness pertaining to collateral ecologic damage, safety issues and antimicrobial stewardship principles, it is critical to describe the unique properties of delafloxacin and define its potential role in therapy. The purpose of this article is to review available data pertaining to delafloxacin's biochemistry, pharmacokinetic/pharmacodynamics characteristics, in vitro activity and potential for resistance selection as well as current progress in clinical trials to ultimately assist clinicians in selecting patients who will benefit most from the distinctive properties of this agent.

  5. Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

    Science.gov (United States)

    Katzenschlager, R; Evans, A; Manson, A; Patsalos, P; Ratnaraj, N; Watt, H; Timmermann, L; Van der Giessen, R; Lees, A

    2004-01-01

    Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (L-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard L-dopa/carbidopa (LD/CD). Methods: Eight Parkinson's disease patients with a short duration L-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. L-Dopa pharmacokinetics were determined, and Unified Parkinson's Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. Results: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak L-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak L-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. Conclusions: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted. PMID:15548480

  6. Pharmacological and clinical evidence of nevirapine immediate- and extended-release formulations

    Directory of Open Access Journals (Sweden)

    Ena J

    2012-11-01

    extended release, efficacy, safety, resistance, clinical practice

  7. A HUMANIZED CLINICALLY CALIBRATED QUANTITATIVE SYSTEMS PHARMACOLOGY MODEL FOR HYPOKINETIC MOTOR SYMPTOMS IN PARKINSON’S DISEASE

    Directory of Open Access Journals (Sweden)

    Hugo eGeerts

    2016-02-01

    Full Text Available The current treatment of Parkinson’s disease with dopamine-centric approaches such as L-DOPA and dopamine agonists, although very succesfull, is in need of alternative treatment strategies, both in terms of disease modification and symptom management. Various non-dopaminergic treatment approaches did not result in a clear clinical benefit, despite showing a clear effect in preclinical animal models. In addition, polypharmacy is common, sometimes leading to unintended effects on non-motor symptoms such as in cognitive and psychiatric domains. To explore novel targets for symptomatic treatment and possible synergistic pharmacodynamic effects between different drugs, we developed a Quantitative Systems Pharmacology (QSP platform of the closed cortico-striatal-thalamic-cortical basal ganglia loop of the dorsal motor circuit. This mechanism-based simulation platform is based on the known neuro-anatomy and neurophysiology of the basal ganglia and explicitly incorporates domain expertise in a formalized way. The calculated beta/gamma power ratio of the local field potential in the subthalamic nucleus correlates well (R2=0.71 with clinically observed extra-pyramidal symptoms triggered by antipsychotics during schizophrenia treatment (43 drug-dose combinations. When incorporating Parkinsonian (PD pathology and reported compensatory changes, the computer model suggests a major increase in b/g ratio (corresponding to bradykinesia and rigidity from a dopamine depletion of 70% onwards. The correlation between the outcome of the QSP model and the reported changes in UPDRS III Motor Part for 22 placebo-normalized drug-dose combinations is R2=0.84. The model also correctly recapitulates the lack of clinical benefit for perampanel, MK-0567 and flupirtine and offers a hypothesis for the translational disconnect. Finally, using human PET imaging studies with placebo response, the computer model predicts well the placebo response for chronic treatment, but not

  8. Modafinil : A Review of its Pharmacology and Clinical Efficacy in the Management of Narcolepsy.

    Science.gov (United States)

    McClellan, K J; Spencer, C M

    1998-04-01

    Modafinil promotes wakefulness through an as yet unknown mechanism of action. It significantly increases daytime sleep latency and reduces excessive daytime sleepiness (EDS) compared with placebo in patients with narcolepsy. However, the drug does not suppress cataplexy. Although direct comparative data are lacking, modafinil offers advantages over amphetamines and methylphenidate in patients with narcolepsy because of its lack of rebound phenomena after treatment withdrawal and its low abuse potential. Clinical trials have shown modafinil to be well tolerated in patients with narcolepsy. Except for headache, which was reported with a significantly greater frequency in modafinil recipients, the tolerability profile of modafinil 200 to 400 mg/day was similar to that of placebo in patients treated for 9 weeks. Preliminary data suggest that the tolerability of modafinil is maintained long term (40 weeks). Thus, modafinil is effective in the treatment of EDS in patients with narcolepsy, although it is not effective against cataplexy. Preliminary findings indicate that, unlike other psychostimulants, the drug is unlikely to be abused and is not associated with withdrawal phenomena. Therefore, modafinil is likely to be an effective therapeutic option for the treatment of EDS in patients with narcolepsy. The mechanism of action of modafinil has not been clearly established. However, it may indirectly increase wakefulness, at least in part, through inhibition of cortical γ-aminobutyric acid (GABA) release via serotonergic mechanisms. Modafinil induces wakefulness and increases locomotor activity in a variety of animal species without causing stereotyped behaviour. In rhesus monkeys, the effects of oral modafinil were not associated with changes in blood pressure or heart rate. In contrast to dexamphetamine 20mg, single night-time doses of modafinil 100 or 200mg had no significant effects on objective sleep variables or sleep structure in young or elderly healthy

  9. Development of innovative teaching materials: clinical pharmacology problem-solving (CPPS) units: comparison with patient-oriented problem-solving units and problem-based learning--a 10-year review.

    Science.gov (United States)

    Lathers, Claire M; Smith, Cedric M

    2002-05-01

    The First Teaching Clinic in Clinical Pharmacology, sponsored by the American College of Clinical Pharmacology in September 1992, was designed for the preparation and development of new clinical pharmacology problem-solving (CPPS) units. CPPS units are case histories that illustrate pertinent principles in clinical pharmacology. Each unit consists of the following sections: introduction, learning objectives, pretest, four clinical pharmacology scenarios, posttest, answers to pre- and posttest questions, and selected references. The clinical pharmacology content of the CPPS units place greater emphasis on clinical information, drug selection, and risk/benefit analyses, and thus they complement the basic pharmacology presented in the patient-oriented problem-solving (POPS) units. In general, the CPPS units are intended for use by students more advanced in clinical pharmacology than first- and second-year medical students. The CPPS unit "Clinical Pharmacology of Antiepileptic Drug Use: Clinical Pearls about the Perils of Patty" was developed for use by third- and fourth-year medical students doing rotations in neurology or clinical pharmacology; advanced pharmacy students; residents in neurology, pediatrics, internal medicine, and family practice; fellows in clinical pharmacology, and those taking the board examination in clinical pharmacology. The CPPS unit titled "Geriatric Clinical Psychopharmacology" was written for third- and fourth-year medical students; residents in psychiatry, family practice, and internal medicine;fellows in clinical pharmacology; and those studying for boards in clinical pharmacology. The CPPS unit "Anisocoria and Glaucoma" was written for more advanced students of clinical pharmacology. The CPPS unit titled "Antiepileptic Drugs" was intended for second-year medical students. The second teaching clinic was held in November 1993 and focused on the development and editing of the CPPS units and their evaluations by faculty and students from

  10. Comparison of the pharmacologic and clinical profiles of new combined oral contraceptives containing estradiol

    Directory of Open Access Journals (Sweden)

    Jensen JT

    2013-11-01

    Full Text Available Jeffrey T Jensen,1 Johannes Bitzer,2 Marco Serrani3 1Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA; 2Department of Social Medicine and Psychosomatics, Women’s Hospital, University Hospital of Basel, Basel, Switzerland; 3Global Medical Affairs, Women’s Healthcare, Bayer HealthCare Pharmaceuticals, Berlin, Germany Abstract: Three estradiol (E2-containing oral contraceptives, estradiol valerate/cyproterone acetate (E2V/CPA, Femilar®, estradiol valerate/dienogest (E2V/DNG, Qlaira®/Natazia™, and estradiol/nomegestrol acetate (E2/NOMAC; Zoely®, have received approval for use in general practice. Only Finnish women currently have access to all three E2-based formulations. E2/NOMAC is currently approved only in Europe, while E2V/DNG is approved globally. To assist clinicians counseling women considering use of one of these formulations, we conducted a review of the published information about the current E2-containing oral contraceptives. A literature search was conducted using the Ovid interface and a combination of free search terms relevant to estradiol and oral contraception to identify suitable articles for inclusion in this review. The available data show that E2V/DNG, E2/NOMAC, and E2V/CPA are all effective oral contraceptives. While direct comparisons are lacking, indirect evidence suggests that E2V/DNG and E2/NOMAC may have better bleeding profiles than E2V/CPA. E2V/DNG is also approved for the treatment of heavy menstrual bleeding. Both E2V/DNG and E2/NOMAC have minimal influence on hemostatic, lipid, and carbohydrate metabolism parameters, or induce less change in these parameters relative to ethinylestradiol-based oral contraceptives. However, the predictive value of these surrogate parameters is a matter of debate, and whether these differences can be translated into meaningful clinical outcomes needs to be established in large-scale, post-marketing, prospective, Phase IV cohort

  11. Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacological Effect of Orally Administered CORT125134: An Adaptive, Double-Blind, Randomized, Placebo-Controlled Phase 1 Clinical Study.

    Science.gov (United States)

    Hunt, Hazel; Donaldson, Kirsteen; Strem, Mark; Zann, Vanessa; Leung, Pui; Sweet, Suzanne; Connor, Alyson; Combs, Dan; Belanoff, Joseph

    2018-05-01

    CORT125134 is an orally active, high-affinity, selective antagonist of the glucocorticoid receptor that is being developed for indications that may benefit from the modulation of cortisol activity. This first-in-human study was conducted to evaluate the dose-related safety, tolerability, pharmacokinetics and pharmacological effects of CORT125134 and its active metabolite CORT125201. Eighty-one healthy male or female subjects received a single dose of 5 to 500 mg CORT125134 or matching placebo across 9 cohorts; 1 cohort received 150 mg CORT125134 after a high-fat breakfast; and 46 subjects received 50 to 500 mg CORT125134 or matching placebo once daily for up to 14 days across 4 cohorts. CORT125134 was well tolerated at doses up to 250 mg per day for 14 days. CORT125134 was absorbed rapidly and eliminated with a mean half-life ranging from 11 to 19 hours. Steady state was achieved by day 7. Exposure increased in a greater than proportional manner, particularly at lower doses. Exposure to CORT125201 at steady state was less than 5% that of parent CORT125134. Evidence for the desired pharmacological effect (glucocorticoid receptor antagonism) was demonstrated by the ability of CORT125134 to prevent several effects of the glucocorticoid receptor agonist prednisone. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  12. Clinical management and gross pathological findings of a severe anaplamosis in a dairy cow

    Directory of Open Access Journals (Sweden)

    Yusuf Abba

    2016-06-01

    Results: The cow did not survive the infection as it eventually died of the disease. Post mortem examination showed gross evidence of splenomegaly, hepatomegaly, distended bile duct and generalized jaundice. Conclusion: Based on the consequence of this case report, preventive vector control, prompt and appropriate treatment and improved management practices are recommended in order to prevent clinical anaplasmosis cases among cattle. [J Adv Vet Anim Res 2016; 3(2.000: 195-199

  13. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline

    Science.gov (United States)

    Sateia, Michael J.; Buysse, Daniel J.; Krystal, Andrew D.; Neubauer, David N.; Heald, Jonathan L.

    2017-01-01

    Introduction: The purpose of this guideline is to establish clinical practice recommendations for the pharmacologic treatment of chronic insomnia in adults, when such treatment is clinically indicated. Unlike previous meta-analyses, which focused on broad classes of drugs, this guideline focuses on individual drugs commonly used to treat insomnia. It includes drugs that are FDA-approved for the treatment of insomnia, as well as several drugs commonly used to treat insomnia without an FDA indication for this condition. This guideline should be used in conjunction with other AASM guidelines on the evaluation and treatment of chronic insomnia in adults. Methods: The American Academy of Sleep Medicine commissioned a task force of four experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, and patient values and preferences. Literature reviews are provided for those pharmacologic agents for which sufficient evidence was available to establish recommendations. The AASM Board of Directors approved the final recommendations. Recommendations: The following recommendations are intended as a guideline for clinicians in choosing a specific pharmacological agent for treatment of chronic insomnia in adults, when such treatment is indicated. Under GRADE, a STRONG recommendation is one that clinicians should, under most circumstances, follow. A WEAK recommendation reflects a lower degree of certainty in the outcome and appropriateness of the patient-care strategy for all patients, but should not be construed as an indication of ineffectiveness. GRADE recommendation strengths do not refer to the magnitude of treatment effects in a particular patient, but rather, to the strength of

  14. Anesthetic pharmacology

    National Research Council Canada - National Science Library

    Evers, Alex S; Maze, M; Kharasch, Evan D

    2011-01-01

    ...: Section 1 introduces the principles of drug action, Section 2 presents the molecular, cellular and integrated physiology of the target organ/functional system and Section 3 reviews the pharmacology...

  15. The pharmacology of neuroplasticity induced by non-invasive brain stimulation: building models for the clinical use of CNS active drugs

    Science.gov (United States)

    Nitsche, Michael A; Müller-Dahlhaus, Florian; Paulus, Walter; Ziemann, Ulf

    2012-01-01

    The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non-invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS-induced plasticity can explore and potentially predict the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment. PMID:22869014

  16. Nem tudo que parece ser, é lesão: aspectos anatômicos, não lesões, artefatos, lesões sem significado clínico e alterações post mortem encontrados na necropsia de suínos domésticos e selvagens (Sus scrofa

    Directory of Open Access Journals (Sweden)

    Raquel R. Rech

    2013-10-01

    Full Text Available A interpretação das alterações encontradas na necropsia é uma etapa importante para o sucesso do diagnóstico final. Este trabalho tem como objetivo descrever e ilustrar os aspectos anatômicos, não lesões, artefatos, lesões sem significado clínico e alterações post mortem encontradas em suínos domésticos e selvagens. Além disso, também se recomenda técnicas de colheita de tecidos para o diagnóstico de doenças que acometem essa espécie. Os principais aspectos anatômicos e não lesões descritos são fímbrias linguais, quadrilátero esofágico, toro pilórico e demarcação do padrão lobular do fígado (sistema gastrintestinal; tonsilas do palato mole, tecido linfoide associado ao estômago, placas de Peyer do intestino delgado e dobras da margem do baço (sistema hematopoiético; mediastino proeminente do testículo e aréolas da placenta (sistema reprodutor; atelectasia pulmonar e apêndice decidual (feto; e glândulas carpais (sistema tegumentar. Os artefatos de eutanásia abordados são petéquias na superfície do pulmão e rim, falsa anemia por sangria, hemorragia subdural por concussão cerebral, pseudo-infartos do baço e aspecto cerebriforme do intestino delgado. As lesões de pouco significado clínico descritas são cistos renais, linfonodos com pigmento de ferro, papilomas e hemangiomas no escroto, ossos no mesentério e hiperemia da mucosa gástrica. As alterações post mortem comumente encontradas são livor mortis, músculos pálidos, pseudomelanose e líquido serosanguinolento nas cavidades torácica e abdominal em fetos.

  17. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline.

    Science.gov (United States)

    Sateia, Michael J; Buysse, Daniel J; Krystal, Andrew D; Neubauer, David N; Heald, Jonathan L

    2017-02-15

    The purpose of this guideline is to establish clinical practice recommendations for the pharmacologic treatment of chronic insomnia in adults, when such treatment is clinically indicated. Unlike previous meta-analyses, which focused on broad classes of drugs, this guideline focuses on individual drugs commonly used to treat insomnia. It includes drugs that are FDA-approved for the treatment of insomnia, as well as several drugs commonly used to treat insomnia without an FDA indication for this condition. This guideline should be used in conjunction with other AASM guidelines on the evaluation and treatment of chronic insomnia in adults. The American Academy of Sleep Medicine commissioned a task force of four experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, and patient values and preferences. Literature reviews are provided for those pharmacologic agents for which sufficient evidence was available to establish recommendations. The AASM Board of Directors approved the final recommendations. The following recommendations are intended as a guideline for clinicians in choosing a specific pharmacological agent for treatment of chronic insomnia in adults, when such treatment is indicated. Under GRADE, a STRONG recommendation is one that clinicians should, under most circumstances, follow. A WEAK recommendation reflects a lower degree of certainty in the outcome and appropriateness of the patient-care strategy for all patients, but should not be construed as an indication of ineffectiveness. GRADE recommendation strengths do not refer to the magnitude of treatment effects in a particular patient, but rather, to the strength of evidence in published data. Downgrading

  18. Lifestyle-oriented non-pharmacological treatments for fibromyalgia: a clinical overview and applications with home-based technologies

    Directory of Open Access Journals (Sweden)

    Friedberg F

    2012-10-01

    Full Text Available Fred Friedberg,1 David A Williams,2 William Collinge31Department of Psychiatry and Behavioral Science, Stony Brook University, Stony Brook, New York; 2Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, 3Collinge and Associates, Kittery, Maine, USAAbstract: Fibromyalgia (FM is a persistent and disabling widespread pain condition often accompanied by chronic fatigue, cognitive problems, sleep disturbance, depression, anxiety, and headache. To date, the most thoroughly studied non-pharmacological approaches to managing FM are those with a focus on changing patient activities and beliefs that affect the illness. These interventions are intended to facilitate enduring improvement in pain and functional status. Lifestyle-oriented treatments include patient education, aerobic or other physical exercise, and cognitive-behavioral therapy (CBT. These interventions in FM can be delivered in medical or behavioral health care settings by trained professionals, through patient-oriented treatment manuals, or via remote-access technologies. Non-pharmacological treatments, in particular exercise and CBT, have yielded effect sizes and cost–benefit ratios comparable to medications. This paper describes lifestyle-oriented non-pharmacological treatments for FM and highlights selected literature reviews of these interventions. In addition, behavioral and practical issues are addressed that may affect these non-pharmacological treatments, including patient expectations, participant burden, and treatment availability. Recommendations are made to facilitate these interventions and potentially improve outcomes. In particular, the increasing availability of convenient home-based mobile technologies to deliver these non-pharmacological treatments is described.Keywords: cognitive-behavior therapy, exercise, education, mobile technology

  19. Necrotizing fasciitis: case series and review of the literature on clinical and medico-legal diagnostic challenges.

    Science.gov (United States)

    Fais, Paolo; Viero, Alessia; Viel, Guido; Giordano, Renzo; Raniero, Dario; Kusstatscher, Stefano; Giraudo, Chiara; Cecchetto, Giovanni; Montisci, Massimo

    2018-04-07

    Necrotizing fasciitis (NF) is a life-threatening infection of soft tissues spreading along the fasciae to the surrounding musculature, subcutaneous fat and overlying skin areas that can rapidly lead to septic shock and death. Due to the pandemic increase of medical malpractice lawsuits, above all in Western countries, the forensic pathologist is frequently asked to investigate post-mortem cases of NF in order to determine the cause of death and to identify any related negligence and/or medical error. Herein, we review the medical literature dealing with cases of NF in a post-mortem setting, present a case series of seven NF fatalities and discuss the main ante-mortem and post-mortem diagnostic challenges of both clinical and forensic interests. In particular, we address the following issues: (1) origin of soft tissue infections, (2) micro-organisms involved, (3) time of progression of the infection to NF, (4) clinical and histological staging of NF and (5) pros and cons of clinical and laboratory scores, specific forensic issues related to the reconstruction of the ideal medical conduct and the evaluation of the causal value/link of any eventual medical error.

  20. Clinical Policy Recommendations from the VHA State-of-the-Art Conference on Non-Pharmacological Approaches to Chronic Musculoskeletal Pain.

    Science.gov (United States)

    Kligler, Benjamin; Bair, Matthew J; Banerjea, Ranjana; DeBar, Lynn; Ezeji-Okoye, Stephen; Lisi, Anthony; Murphy, Jennifer L; Sandbrink, Friedhelm; Cherkin, Daniel C

    2018-05-01

    As a large national healthcare system, Veterans Health Administration (VHA) is ideally suited to build on its work to date and develop a safe, evidence-based, and comprehensive approach to the care of chronic musculoskeletal pain conditions that de-emphasizes opioid use and emphasizes non-pharmacological strategies. The VHA Office of Health Services Research and Development (HSR&D) held a state-of-the-art (SOTA) conference titled "Non-pharmacological Approaches to Chronic Musculoskeletal Pain Management" in November 2016. Goals of the conference were (1) to establish consensus on the current state of evidence regarding non-pharmacological approaches to chronic musculoskeletal pain to inform VHA policy in this area and (2) to begin to identify priorities for the future VHA research agenda. Workgroups were established and asked to reach consensus recommendations on clinical and research priorities for the following treatment strategies: psychological/behavioral therapies, exercise/movement therapies, manual therapies, and models for delivering multimodal pain care. Participants in the SOTA identified nine non-pharmacological therapies with sufficient evidence to be implemented across the VHA system as part of pain care. Participants further recommended that effective integration of these non-pharmacological approaches across the VHA and especially into VHA primary care, pain care, and mental health settings should be a priority, and that these treatments should be offered early in the course of pain treatment and delivered in a team-based, multimodal treatment setting concurrently with active self-care and self-management approaches. In addition, we recommend that VHA leadership and policy makers systematically address the barriers to implementation of these approaches by expanding opportunities for clinician and veteran education on the effectiveness of these strategies; supporting and funding further research to determine optimal dosage, duration, sequencing

  1. Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

    Science.gov (United States)

    Wilt, Timothy J; MacDonald, Roderick; Brasure, Michelle; Olson, Carin M; Carlyle, Maureen; Fuchs, Erika; Khawaja, Imran S; Diem, Susan; Koffel, Erin; Ouellette, Jeannine; Butler, Mary; Kane, Robert L

    2016-07-19

    Pharmacologic interventions are often prescribed for insomnia disorder. To assess the benefits, harms, and comparative effectiveness of pharmacologic treatments for adults with insomnia disorder. Several electronic databases (2004-September 2015), reference lists, and U.S. Food and Drug Administration (FDA) documents. 35 randomized, controlled trials of at least 4 weeks' duration that evaluated pharmacotherapies available in the United States and that reported global or sleep outcomes; 11 long-term observational studies that reported harm information; FDA review data for nonbenzodiazepine hypnotics and orexin receptor antagonists; and product labels for all agents. Data extraction by single investigator confirmed by a second reviewer; dual-investigator assessment of risk of bias; consensus determination of strength of evidence. Eszopiclone, zolpidem, and suvorexant improved short-term global and sleep outcomes compared with placebo, although absolute effect sizes were small (low- to moderate-strength evidence). Evidence for benzodiazepine hypnotics, melatonin agonists, and antidepressants, and for most pharmacologic interventions in older adults, was insufficient or low strength. Evidence was also insufficient to compare efficacy within or across pharmacotherapy classes or versus behavioral therapy. Harms evidence reported in trials was judged insufficient or low strength; observational studies suggested that use of hypnotics for insomnia was associated with increased risk for dementia, fractures, and major injury. The FDA documents reported that most pharmacotherapies had risks for cognitive and behavioral changes, including driving impairment, and other adverse effects, and they advised dose reduction in women and in older adults. Most trials were small and short term and enrolled individuals meeting stringent criteria. Minimum important differences in outcomes were often not established or reported. Data were scant for many treatments. Eszopiclone, zolpidem, and

  2. Post mortem analysis of fatigue mechanisms in LiNi0.8Co0.15Al0.05O2 - LiNi0.5Co0.2Mn0.3O2 - LiMn2O4/graphite lithium ion batteries

    Science.gov (United States)

    Lang, Michael; Darma, Mariyam Susana Dewi; Kleiner, Karin; Riekehr, Lars; Mereacre, Liuda; Ávila Pérez, Marta; Liebau, Verena; Ehrenberg, Helmut

    2016-09-01

    The fatigue of commercial lithium ion batteries after long-term cycling at two different temperatures and cycling rates is investigated. The cells are opened after cycling and post-mortem analysis are conducted. Two main contributions to the capacity loss of the batteries are revealed. The loss of active lithium leads to a relative shift between anodes and cathodes potentials. A growth of the solid electrolyte interface (SEI) on the anode is determined as well as the formation of lithium fluoride species as an electrolyte decomposition product. Those effects are reinforced by increasing cycling rates from 1C/2C (charge/discharge) to 2C/3C as well as by increasing cycling temperatures from 25 °C to 40 °C. The other contribution to the capacity loss originates from a fatigue of the blended cathodes consisting of LiNi0.5Co0.2Mn0.3O2 (NCM), LiNi0.8Co0.15Al0.05O2 (NCA) and LiMn2O4 (LMO). Phase-specific capacity losses and fatigue mechanisms are identified. The layered oxides tend to form microcracks and reveal changes of the surface structure leading to a worsening of the lithium kinetics. The cathode exhibits a loss of manganese at 40 °C cycling temperature. Cycling at 40 °C instead of 25 °C has the major impact on cathodes capacity loss, while cycling at 2C/3C rates barely influences it.

  3. [Pharmacological treatment].

    Science.gov (United States)

    Arriola Manchola, Enrique; Álaba Trueba, Javier

    2016-06-01

    Alzheimer's disease (AD) is a chronic degenerative and inflammatory process leading to synapticdysfunction and neuronal death. A review about the pharmacological treatment alternatives is made: acetylcholinesterase inhibitors (AChEI), a nutritional supplement (Souvenaid) and Ginkgo biloba. A special emphasis on Ginkgo biloba due to the controversy about its use and the approval by the European Medicines Agency is made. Copyright © 2016 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Post-mortem findings in Irish culled hounds.

    Science.gov (United States)

    Jahns, H; Callanan, J J; McElroy, M C; Sammin, D J; Bassett, H F

    2011-07-01

    Little is known of the common diseases of hunting dogs or of the reasons why they are culled. To address these questions, necropsy examinations were conducted on 52 hounds aged 1.5-12 years (mean 6.5 ± 2.5 years) and culled from 10 Irish hunting kennels over a 3-year period. Progressive systemic disease was seen in six dogs only and encompassed individual cases of tuberculosis caused by Mycobacterium bovis, bronchioalveolar carcinoma with metastasis to regional lymph nodes, renal amyloidosis, suppurative pneumonia, extramedullary plasmacytoma in the atrial wall of the heart and foreign body-induced hepatitis with focal peritonitis. Single or multiple localized tumours were identified in five dogs and, apart from the aforementioned, included two cutaneous haemangiomas, a trichoepithelioma, a lipoma and a mammary ductal adenoma. Three dogs were culled for lameness; one of these dogs had torn musculature, another had cellulitis and the third had a healed fracture of the tibia and fibula. Chronic renal changes were present in 48% of the dogs and included focal proliferative, exudative or crescentic glomerulonephritis (33%) or low-grade interstitial inflammatory changes (50%). The most frequently diagnosed skin lesions reported in this study were mild healed decubitus ulcers (33%), scars (33%) and stereotypic dermatitis (13%). These findings indicate that hounds are likely to be culled for reasons other than the presence of disease in most cases. In addition, this survey highlights different disease patterns in hounds than are typically observed in pet dogs. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Post mortem analysis of a JET quartz microbalance system

    Energy Technology Data Exchange (ETDEWEB)

    Esser, H.G. [Association EURATOM-Forschungszentrum Juelich, IPP, D-52425, Juelich (Germany)]. E-mail: h.g.esser@fz-juelich.de; Philipps, V. [Association EURATOM-Forschungszentrum Juelich, IPP, D-52425, Juelich (Germany); Wienhold, P. [Association EURATOM-Forschungszentrum Juelich, IPP, D-52425, Juelich (Germany); Sugiyama, K. [Department of Nuclear Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan); Kreter, A. [Association EURATOM-Forschungszentrum Juelich, IPP, D-52425, Juelich (Germany); Coad, J.P. [UKAEA/EURATOM Fusion Association, Culham Science Centre, Abingdon (United Kingdom); Tanabe, T. [Department of Nuclear Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan)

    2007-06-15

    In the year 2001, a quartz microbalance system (QMB) was installed in the remote area of the inner JET divertor to investigate in situ material erosion and redeposition processes. When removed in 2004, the system was found to be coated all over with carbon deposits. The deposit on the quartz oscillator and the outer and inner housing was analysed by various methods, as SIMS (secondary ion mass spectroscopy), stylus depth profilometry, EPMA (electron probe microanalysis), TIPT (Tritium imaging plate technique) and colorimetry and compared to the frequency change of the quartz. The layer thickness was determined to 1.85 {+-} 0.1 {mu}m in average on an area of 0.95 cm{sup 2} which has to be related to the equivalent of 1.77 x 10{sup -4} g measured from the frequency change of 23 640 Hz. This corresponds to a carbon areal density of 9.3 x 10{sup 18} C atoms/cm{sup 2}. Significant deposition was found also on the surfaces inside the QMB housing which can only be understood if reflection and low sticking is assumed for a high fraction of particles.

  6. FEBEX Project Post-mortem Analysis: Corrosion Study

    International Nuclear Information System (INIS)

    Madina, V.; Azkarate, I.

    2004-01-01

    The partial dismantling of the FEBEX in situ test was carried out during de summer of 2002, following 5 years of continuous heating. The operation included the demolition of the concrete plug and the removal of the section of the test corresponding to the first heater. A large number of samples from all types of materials have been taken during the dismantling for subsequent analysis. Part of the samples collected were devoted to the analysis of the corrosion processes occurred during the first operational phase of the test. These samples comprised corrosion coupons from different metals installed for that purpose, sensors retrieved during the dismantling that were found severely corroded and bentonite in contact with those sensors. In addition, a corrosion study was performed on the heater extracted and on one section of liner surrounding it. All the analyses were carried out by the Fundacion INASMET (Spain). This report describes, in detail the studies carried out the different materials and the obtained results, as well as the drawn conclusions. (Author)

  7. FEBEX II Project Post-mortem analysis EDZ assessment

    International Nuclear Information System (INIS)

    Bazargan Sabet, B.; Shao, H.; Autio, J.; Elorza, F. J.

    2004-01-01

    Within the framework of the FEBEX II project a multidisciplinary team studied the mechanisms of creation of the potential damaged zone around the test drift. The research program includes laboratory and in situ investigations as well as the numerical modelling of the observed phenomena. Where laboratory investigations are concerned, the 14C-PMMA technique was applied to study the spatial distribution of porosity in the samples taken from the test drift wall. In addition complementary microscopy and scanning electron microscopy (SEM) studies were performed to make qualitative investigations on the pore apertures and minerals in porous regions. The results obtained with the PMMA method have not shown any clear increased porosity zone adjacent to the tunnel wall. The total porosity of the samples varied between 0.6-1.2%. The samples of unplugged region did not differ from the samples of plugged region. A clear increase in porosity to depths of 10-15 mm from the tunnel wall was detected in lamprophyre samples. According to the SEM/EDX analyses the excavation-disturbed zone in the granite matrix extended to depths of 1-3 mm from the wall surface. A few quartz grains were crushed and some micro fractures were found. Gas permeability tests were carried out on two hollow cylinder samples of about 1m long each taken on the granite wall perpendicular to the drift axis. The first sample was cored in the service area far from the heated zone and the second one at the level of the heater. The tests were performed at constant gas pressure by setting a steady state radial flow through a section of 1cm wide isolated by means of four mini-packers. The profile of the gas permeability according to the core length has been established. The results obtained for both considered samples have shown permeability ranging between 3.5 10-18 and 8.4 10-19m2, pointing out the absence of a marked damage. Acoustic investigations have been carried out with the objective of quantifying the variations in the propagation velocities of acoustic waves. A cylindrical block of granite 38.8 cm in diameter and 40 cm high has been analysed along 2D transversal sections in six radial directions. Different inverse tomographic strategies have been used to analyse the measured data, which shown no evidences of the existence of an EDZ in FEBEX gallery. However, a preferential direction in the wave propagation similar to the maximum compression direction of the stress tensor has appeared. As for in situ investigations, the hydraulic connectivity of the drift has been assessed at eleven locations in heated area, including granite matrix and lamprophyre dykes and at six locations in undisturbed zones. In the granite matrix area, pulse test using pressurised air with stepwise pressure increasing was conducted to determine gas entry pressure. In the fractured area, a gas constant flow rate injection test was conducted. Only two locations with higher permeability were detected; one in a natural fracture in the lamprophyre dyke and the other in the interface between lamprophyre and granite. Where numerical investigations are concerned, several analyses of the FEBEX in situ experiment were carried ou