TB research at UT-Houston--a review of cord factor: new approaches to drugs, vaccines and the pathogenesis of tuberculosis.

Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain unanswered. This paper reviews research dating back to the 1950's providing compelling evidence that cord factor (trehalose 6,6 dimycolate [TDM]) is essential for understanding tuberculosis. However, the original papers by Bloch and Noll were too far ahead of their time to have immediate impact. We can now recognize that the physical and biologic properties of cord factor are unprecedented in science, especially its ability to switch between two sets of biologic activities with changes in conformation. While TDM remains on organisms, it protects them from killing within macrophages, reduces antibiotic effectiveness and inhibits the stimulation of protective immune responses. If it comes off organisms and associates with lipid, TDM becomes a driver of tissue damage and necrosis. Studies emanating from cord factor research have produced (1) a rationale for improving vaccines, (2) an approach to new drugs that overcome natural resistance to antibiotics, (3) models of caseating granulomas that reproduce multiple manifestations of human tuberculosis. (4) evidence that TDM is a key T cell antigen in destructive lesions of tuberculosis, and (5) a new understanding of the pathology and pathogenesis of postprimary tuberculosis that can guide more informative studies of long standing mysteries of tuberculosis.

Development, implementation, and evaluation of a structured reporting web tool for abdominal aortic aneurysms

BACKGROUND The majority of radiological reports are lacking a standard structure. Even within a specialized area of radiology, each report has its individual structure with regards to details and order, often containing too much of non-relevant information the referring physician is not interested in. For gathering relevant clinical key parameters in an efficient way or to support long-term therapy monitoring, structured reporting might be advantageous. OBJECTIVE Despite of new technologies in medical information systems, medical reporting is still not dynamic. To improve the quality of communication in radiology reports, a new structured reporting system was developed for abdominal aortic aneurysms (AAA), intended to enhance professional communication by providing the pertinent clinical information in a predefined standard. METHODS Actual state analysis was performed within the departments of radiology and vascular surgery by developing a Technology Acceptance Model. The SWOT (strengths, weaknesses, opportunities, and threats) analysis focused on optimization of the radiology reporting of patients with AAA. Definition of clinical parameters was achieved by interviewing experienced clinicians in radiology and vascular surgery. For evaluation, a focus group (4 radiologists) looked at the reports of 16 patients. The usability and reliability of the method was validated in a real-world test environment in the field of radiology. RESULTS A Web-based application for radiological "structured reporting" (SR) was successfully standardized for AAA. Its organization comprises three main categories: characteristics of pathology and adjacent anatomy, measurements, and additional findings. Using different graphical widgets (eg, drop-down menus) in each category facilitate predefined data entries. Measurement parameters shown in a diagram can be defined for clinical monitoring and be adducted for quick adjudications. Figures for optional use to guide and standardize the reporting are embedded. Analysis of variance shows decreased average time required with SR to obtain a radiological report compared to free-text reporting (P=.0001). Questionnaire responses confirm a high acceptance rate by the user. CONCLUSIONS The new SR system may support efficient radiological reporting for initial diagnosis and follow-up for AAA. Perceived advantages of our SR platform are ease of use, which may lead to more accurate decision support. The new system is open to communicate not only with clinical partners but also with Radiology Information and Hospital Information Systems.

Multi-phase postmortem CT angiography: recognizing technique-related artefacts and pitfalls

BACKGROUND AND PURPOSE Multi-phase postmortem CT angiography (MPMCTA) is increasingly being recognized as a valuable adjunct medicolegal tool to explore the vascular system. Adequate interpretation, however, requires knowledge about the most common technique-related artefacts. The purpose of this study was to identify and index the possible artefacts related to MPMCTA. MATERIAL AND METHODS An experienced radiologist blinded to all clinical and forensic data retrospectively reviewed 49 MPMCTAs. Each angiographic phase, i.e. arterial, venous and dynamic, was analysed separately to identify phase-specific artefacts based on location and aspect. RESULTS Incomplete contrast filling of the cerebral venous system was the most commonly encountered artefact, followed by contrast agent layering in the lumen of the thoracic aorta. Enhancement or so-called oedematization of the digestive system mucosa was also frequently observed. CONCLUSION All MPMCTA artefacts observed and described here are reproducible and easily identifiable. Knowledge about these artefacts is important to avoid misinterpreting them as pathological findings.

ISVI-IUA consensus document - diagnostic guidelines on vascular anomalies: vascular malformations and hemangiomas.

The diagnostic approach to vascular anomalies should include the distinction between vascular tumors (i.e. hemangiomas) and congential vascular malformations (CVMs). This step is based more on history and clinical examination rather than on instrumental evaluation. In children Duplex ultrasound and histology can be helpful to separate hypervasularized tumors from CVMs. Appropriate record of objective measures as size or flow volume is required in order to evaluate the progress of the pathology and/or to assess the results of adopted therapeutic interventions. The anatomic, pathological and hemodynamic characteristics, the secondary effects on the surrounding tissues and the systemic manifestations should be defined. Basic diagnostic tools are Duplex sonography followed by MRI or CT scanning. The definition of the vascular anomaly should be according to the Hamburg classification and should separate vascular tumors from vacular malformations followed by separation of high flow from low flow CVMs. Diagnostic investigations are best undertaken at centers where subsequent therapeutic interventions will be performed.

Self-burning – A rare suicide method in switzerland and other industrialised nations – A review

News items reporting self-immolation by Tibetans have been on the increase in recent years. After examining the corpse of a Swiss man who had committed suicide by deliberate self-burning, we wondered how often this occurs in Switzerland. The Federal Statistics Office (FSO) does not register self-burning specifically so no official national data on this form of suicide are available. However, we had access to the data from a Swiss National Science Foundation (SNSF) project Suicides in Switzerland between 2000 and 2010, which collected information on all (4885) cases of suicide investigated by the various institutes of forensic medicine. From this data pool we extracted 50 cases (1.02%) of suicide by selfburning, in order to determine the details and to identify the possible reasons for choosing this method. To look at our results in the light of studies from other countries, we searched the literature for studies that had also retrospectively examined suicide by self-immolation based on forensic records. Our results showed that, on the whole, personal aspects of selfburning in Switzerland do not differ from those in other industrialised nations. Some data, including religious and sociocultural background, were unfortunately missing – not only from our study but also from the similar ones. In our opinion, the most important prevention strategy is to make healthcare professionals more aware of this rare method of suicide.

Detection and quantification of 56 new psychoactive substances in whole blood and urine by LC-MS/MS

BACKGROUND New psychoactive substances (NPS) have become increasingly prevalent and are sold in internet shops as 'bath salts' or 'research chemicals' and comprehensive bioanalytical methods are needed for their detection. METHODOLOGY We developed and validated a method using LC and MS/MS to quantify 56 NPS in blood and urine, including amphetamine derivatives, 2C compounds, aminoindanes, cathinones, piperazines, tryptamines, dissociatives and others. Instrumentation included a Synergi Polar-RP column (Phenomenex) and a 3200 QTrap mass spectrometer (AB Sciex). Run time was 20 min. CONCLUSION A novel method is presented for the unambiguous identification and quantification of 56 NPS in blood and urine samples in clinical and forensic cases, e.g., intoxications or driving under the influence of drugs.

Fatal steamer accident; blunt force injuries and drowning in post-mortem MSCT and MRI.

Steamer accidents, through contact with the bucket wheel, are very seldom today. No publication of such a kind of fatal accident could be found in literature. We present the case of a fatal steamer accident, in which the findings of a blunt traumatization of a person by the ship was completely documented by post-mortem combined multi-slice computed tomography (MSCT) and magnetic resonance imaging (MRI) examinations. A rupture of the aorta was detected using both radiological methods without use of radiopaque material. Radiological examination revealed a comminuted fracture of the thorax vertebrae at the same level as the aortic rupture. Injuries of the soft tissues of the back, caused by the bucket wheel of the steamer, were also diagnosed. In addition to the signs of blunt force trauma the findings of drowning such as an over inflation of the lungs, fluid in the stomach and duodenum were revealed. Furthermore, algological analysis detected diatoms in the lung tissue and blood from the left heart. Therefore, the cause of death was considered being a combination of fatal hemorrhage, caused by the aortic rupture, and drowning. We conclude that virtual autopsy using combined post-mortem MSCT and MRI is a useful tool for documentation, visualisation and analysis of the findings of blunt force trauma and drowning with a large potential in forensic medicine.

Postmortem diagnostics using MSCT and MRI of a lethal streptococcus group A infection at infancy: a case report.

Postmortem cross-sectional imaging using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) was considered as a base for a minimal invasive postmortem investigation in forensic medicine such as within the Virtopsy approach. We present the case of a 3-year-old girl with a lethal streptococcus group A infection and the findings of postmortem imaging in this kind of natural death. Postmortem MSCT and MRI revealed an edematous occlusion of the larynx at the level of the vocal cords, severe pneumonia with atelectatic parts of both upper lobes and complete atelectasis of both lower lobes, purulent fluid-filled right main bronchus, enlargement of cervical lymph nodes and pharyngeal tonsils, and additionally, a remaining glossopharyngeal cyst as well as an ureter fissus of the right kidney. All relevant autopsy findings could be obtained and visualized by postmortem imaging and confirmed by histological and microbiological investigations supporting the idea of a minimal invasive autopsy technique.

Virtopsy: postmortem imaging of the human heart in situ using MSCT and MRI.

The rapid further development of computed tomography (CT) and magnetic resonance imaging (MRI) induced the idea to use these techniques for postmortem documentation of forensic findings. Until now, only a few institutes of forensic medicine have acquired experience in postmortem cross-sectional imaging. Protocols, image interpretation and visualization have to be adapted to the postmortem conditions. Especially, postmortem alterations, such as putrefaction and livores, different temperature of the corpse and the loss of the circulation are a challenge for the imaging process and interpretation. Advantages of postmortem imaging are the higher exposure and resolution available in CT when there is no concern for biologic effects of ionizing radiation, and the lack of cardiac motion artifacts during scanning. CT and MRI may become useful tools for postmortem documentation in forensic medicine. In Bern, 80 human corpses underwent postmortem imaging by CT and MRI prior to traditional autopsy until the month of August 2003. Here, we describe the imaging appearance of postmortem alterations--internal livores, putrefaction, postmortem clotting--and distinguish them from the forensic findings of the heart, such as calcification, endocarditis, myocardial infarction, myocardial scarring, injury and other morphological alterations.

Usage of Complementary Medicine in Switzerland: Results of the Swiss Health Survey 2012 and Development Since 2007

Background Complementary medicine (CM) is popular in Switzerland. Several CM methods (traditional Chinese medicine/acupuncture, homeopathy, anthroposophic medicine, neural therapy, and herbal medicine) are currently covered by the mandatory basic health insurance when performed by a certified physician. Treatments by non-medical therapists are partially covered by a supplemental and optional health insurance. In this study, we investigated the frequency of CM use including the evolvement over time, the most popular methods, and the user profile. Methods Data of the Swiss Health Surveys 2007 and 2012 were used. In 2007 and 2012, a population of 14,432 and 18,357, respectively, aged 15 years or older answered the written questionnaire. A set of questions queried about the frequency of use of various CM methods within the last 12 months before the survey. Proportions of usage and 95% confidence intervals were calculated for these methods and CM in general. Users and non-users of CM were compared using logistic regression models. Results The most popular methods in 2012 were homeopathy, naturopathy, osteopathy, herbal medicine, and acupuncture. The average number of treatments within the 12 months preceding the survey ranged from 3 for homeopathy to 6 for acupuncture. 25.0% of the population at the age of 15 and older had used at least one CM method in the previous 12 months. People with a chronic illness or a poor self-perceived health status were more likely to use CM. Similar to other countries, women, people of middle age, and those with higher education were more likely to use CM. 59.9% of the adult population had a supplemental health insurance that partly covered CM treatments. Conclusions Usage of CM in Switzerland remained unchanged between 2007 and 2012. The user profile in Switzerland was similar to other countries, such as Germany, United Kingdom, United States or Australia.

The role of anti-VEGF agents in myopic choroidal neovascularization: Current standards and future outlook

Introduction The global prevalence of pathologic myopia is 0.9-3.1%, and visual impairment is found in 0.1-0.5% of European and 0.2-1.4% of Asian studies. Myopic choroidal neovascularization (mCNV) affects 5.2-11.3% of pathologic myopia patients and is a leading cause of vision impairment in the working-age population. Characteristic morphological changes and visual-acuity decrease are diagnostic features. Vascular-Endothelial-Growth-Factor (VEGF) has been identified as a trigger for pathologic neovascularization in these highly myopic patients. Areas Covered We cover the epidemiology, pathology and diagnostic aspects of mCNV. The history of therapeutic interventions is described, followed by an overview of current standard-of-care (SOC)-blocking VEGF using bevacizumab (off-label), ranibizumab or aflibercept and improving vision up to 13.5-14.4 letters. Despite good efficacy, an unmet medical need remains. We summarize ongoing and future developments of new drugs to treat or potentially cure mCNV. Expert Opinion mCNV is a major global health concern. Early detection and treatment is key for a satisfying outcome. The current SOC, VEGF inhibitors, affords good therapeutic efficacy and reasonable disease stabilization with few intravitreal treatments per year. However, the long-term prognosis is still unsatisfactory, and side-effects like chorioretinal atrophy development are of concern. Therefore, efforts should be intensified to develop more effective therapies.

Post mortem computed tomography and core needle biopsy in comparison to autopsy in eleven bernese mountain Dogs with histiocytic sarcoma

Background: Bernese mountain dogs are reported to have a shorter life expectancy than other breeds. A Major reason for this has been assigned to a high tumour prevalence, especially of histiocytic sarcoma. The efforts made by the breeding clubs to improve the longevity with the help of genetic tests and breeding value estimations are impeded by insufficiently reliable diagnoses regarding the cause of death. The current standard for post mortem examination in animals is performance of an autopsy. In human forensic medicine, imaging modalities, such as computed tomography and magnetic resonance imaging, are used with increasing frequency as a complement to autopsy. The present study investigates, whether post mortem computed tomography in combination with core needle biopsy is able to provide a definitive diagnosis of histiocytic sarcoma. For this purpose we have analysed the results of post mortem computed tomography and core needle biopsy in eleven Bernese mountain dogs. In the subsequent autopsy, every dog had a definitive diagnosis of histiocytic sarcoma, based on immunohistochemistry. Results: Computed tomography revealed space-occupying lesions in all dogs. Lesion detection by post mortem computed tomography was similar to lesion detection in autopsy for lung tissue (9 cases in computed tomography / 8 cases in autopsy), thoracic lymph nodes (9/8), spleen (6/7), kidney (2/2) and bone (3/3). Hepatic nodules, however, were difficult to detect with our scanning protocol (2/7). Histology of the core needle biopsies provided definitive diagnoses of histiocytic sarcoma in ten dogs, including confirmation by immunohistochemistry in six dogs. The biopsy samples of the remaining dog did not contain any identifiable neoplastic cells. Autolysis was the main reason for uncertain histological diagnoses. Conclusions: Post mortem computed tomography is a fast and effective method for the detection of lesions suspicious for histiocytic sarcoma in pulmonary, thoracic lymphatic, splenic, osseous and renal tissue. Optimization of the procedure regarding the scanning protocol and tissue sample size and number will improve the accuracy of the method. Keywords: Post mortem computed tomography, Core needle biopsy, Bernese mountain dog, Histiocytic sarcoma, Autopsy

Smaller but denser: postmortem changes alter the CT characteristics of subdural hematomas

PURPOSE The aim of this study was to investigate if (1) the volume of subdural hematomas (SDH), midline shift, and CT density of subdural hematomas are altered by postmortem changes and (2) if these changes are dependent on the postmortem interval (PMI). MATERIALS AND METHODS Ante mortem computed tomography (AMCT) of the head was compared to corresponding postmortem CT (PMCT) in 19 adults with SDH. SDH volume, midline shift, and hematoma density were measured on both AMCT and PMCT and their differences assessed using Wilcoxon-Signed Rank Test. Spearman's Rho Test was used to assess significant correlations between the PMI and the alterations of SDH volume, midline shift, and hematoma density. RESULTS Mean time between last AMCT and PMCT was 109 h, mean PMI was 35 h. On PMCT mean midline displacement was decreased by 57% (p < 0.001); mean SDH volume was decreased by 38% (p < 0.001); and mean hematoma density was increased by 18% (p < 0.001) in comparison to AMCT. There was no correlation between the PMI and the normalization of the midline shift (p = 0.706), the reduction of SDH volume (p = 0.366), or the increase of hematoma density (p = 0.140). CONCLUSIONS This study reveals that normal postmortem changes significantly affect the extent and imaging characteristics of subdural hematoma and may therefore affect the interpretation of these findings on PMCT. Radiologists and forensic pathologists who use PMCT must be aware of these phenomena in order to correctly interpret PMCT findings in cases of subdural hemorrhages.

Computer-assisted virtual autopsy using surgical navigation techniques

UNLABELLED OBJECTIVE; Virtual autopsy methods, such as postmortem CT and MRI, are increasingly being used in forensic medicine. Forensic investigators with little to no training in diagnostic radiology and medical laypeople such as state's attorneys often find it difficult to understand the anatomic orientation of axial postmortem CT images. We present a computer-assisted system that permits postmortem CT datasets to be quickly and intuitively resliced in real time at the body to narrow the gap between radiologic imaging and autopsy. CONCLUSION Our system is a potentially valuable tool for planning autopsies, showing findings to medical laypeople, and teaching CT anatomy, thus further closing the gap between radiology and forensic pathology.