Pharmacokinetics and clinical efficacy of cyclosporine treatment of dogs with steroid-refractory inflammatory bowel disease

The usual treatment of dogs with inflammatory bowel disease (IBD) consists of administration of immunosuppressive doses of steroids. However, some dogs are refractory to steroid treatment and pose a significant challenge to the veterinarian. Because cyclosporine A (cyA) has been shown to be effective in steroid-resistant IBD in humans, the purpose of this study was to investigate the pharmacokinetics and clinical efficacy of PO cyA treatment in dogs with steroid-refractory IBD (n = 14). All dogs were treated with cyA 5 mg/kg PO q24h for a period of 10 weeks. A clinical activity score was assigned to assess severity of clinical signs before and after treatment. The total number of infiltrating lymphocytes and T cells in duodenal biopsies were assessed before and after treatment in 9 dogs. In addition, serum concentration of cyA was measured in 8 dogs over a 24-hour period. Pharmacokinetic profiles in dogs with IBD were similar to those of healthy dogs. Improvement of clinical signs was observed in 12 of 14 dogs with IBD. Median clinical activity score after treatment with cyA was significantly reduced from a median score of 9 to a median score of 5 (P = 0.001). T cell numbers in duodenal biopsies were significantly decreased after treatment from a median +/- 95% range in the villous region of 28 (19-30) cells/10,000 microm2 before versus 7 (0-10)/10,000 microm2 after treatment, P = 0.01; and from a median +/- 95% range number in the crypt region of 15 (6-23) cells/10,000 microm2 before versus 4 (0-9)/10,000 microm2 after treatment, P = 0.02, implying T cell lysis as a possible mechanism of action. In conclusion, based on this small study, cyA appears to be an effective alternative drug in dogs with IBD that are refractory to immunosuppressive doses of steroids.

Post-mortem tissue sampling using computed tomography guidance

PURPOSE: Currently, in forensic medicine cross-sectional imaging gains recognition and a wide use as a non-invasive examination approach. Today, computed tomography (CT) or magnetic resonance imaging that are available for patients are unable to provide tissue information on the cellular level in a non-invasive manner and also diatom detection, DNA, bacteriological, chemical toxicological and other specific tissue analyses are impossible using radiology. We hypothesised that post-mortem minimally invasive tissue sampling using needle biopsies under CT guidance might significantly enhance the potential of virtual autopsy. The purpose of this study was to test the use of a clinically approved biopsy needle for minimally invasive post-mortem sampling of tissue specimens under CT guidance. MATERIAL AND METHODS: ACN III biopsy core needles 14 gauge x 160 mm with automatic pistol device were used on three bodies dedicated to research from the local anatomical institute. Tissue probes from the brain, heart, lung, liver, spleen, kidney and muscle tissue were obtained under CT fluoroscopy. RESULTS: CT fluoroscopy enabled accurate placement of the needle within the organs and tissues. The needles allowed for sampling of tissue probes with a mean width of 1.7 mm (range 1.2-2 mm) and the maximal length of 20 mm at all locations. The obtained tissue specimens were of sufficient size and adequate quality for histological analysis. CONCLUSION: Our results indicate that, similar to the clinical experience but in many more organs, the tissue specimens obtained using the clinically approved biopsy needle are of a sufficient size and adequate quality for a histological examination. We suggest that post-mortem biopsy using the ACN III needle under CT guidance may become a reliable method for targeted sampling of tissue probes of the body.

Postmortem radiology of fatal hemorrhage: measurements of cross-sectional areas of major blood vessels and volumes of aorta and spleen on MDCT and volumes of heart chambers on MRI

OBJECTIVE: Autopsy determination of fatal hemorrhage as the cause of death is often a difficult diagnosis in forensic medicine. No quantitative system for accurately measuring the blood volume in a corpse has been developed. MATERIALS AND METHODS: This article describes the measurement and evaluation of the cross-sectional areas of major blood vessels, of the diameter of the right pulmonary artery, of the volumes of thoracic aorta and spleen on MDCT, and of the volumes of heart chambers on MRI in 65 autopsy-verified cases of fatal hemorrhage or no fatal hemorrhage. RESULTS: Most cases with a cause of death of "fatal hemorrhage" had collapsed vessels. The finding of a collapsed superior vena cava, main pulmonary artery, or right pulmonary artery was 100% specific for fatal hemorrhage. The mean volumes of the thoracic aorta and of each of the heart chambers and the mean cross-sectional areas of all vessels except the inferior vena cava and abdominal aorta were significantly smaller in fatal hemorrhage than in no fatal hemorrhage. CONCLUSION: For the quantitative differentiation of fatal hemorrhage from other causes of death, we propose a three-step algorithm with measurements of the diameter of the right pulmonary artery, the cross-sectional area of the main pulmonary artery, and the volume of the right atrium (specificity, 100%; sensitivity, 95%). However, this algorithm must be corroborated in a prospective study, which would eliminate the limitations of this study. Quantitative postmortem cross-sectional imaging might become a reliable objective method to assess the question of fatal hemorrhage in forensic medicine.

Virtopsy hemorrhage of the posterior cricoarytenoid muscle by blunt force to the neck in postmortem multislice computed tomography and magnetic resonance imaging

In forensic autopsies, one of the most important and common signs of violence to the neck is hemorrhages of the soft tissues. The Institute of Forensic Medicine in Bern evaluates the usefulness of postmortem multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) of forensic cases prior to autopsy. The aim of this study was to prove the sensitivity of postmortem MSCT and MRI in the detection of hemorrhages of the neck muscles. A full body scan prior to and a detailed scan of the explanted larynx after autopsy were performed. MSCT detected multiple fractures of the larynx. Detailed MRI was able to demonstrate the hemorrhage of the left posterior cricoarytenoid muscle. The minor hemorrhage of the right posterior cricoarytenoid muscle could not be detected with certainty. Although more experience is required, we conclude that combined MRI and MSCT examination is a useful tool for documentation and examination of neck muscle hemorrhages in forensic cases.

The deadly broomstick: an unusual missile injury to the neck

A 51-year-old man was struck by the tip of a broomstick weighing 1000 g at the left side of the neck, upon which he collapsed. Intense but delayed cardiopulmonary resuscitation restored the circulation roughly 30 minutes after the incident. Upon admittance to a nearby hospital, an extensive hypoxic cerebral damage was diagnosed. Death due to the severe cerebral damage occurred 5 hours after the incident. An autopsy demonstrated a severe subcutaneous traumatization of the left side of the neck, with a hemorrhage compressing the carotid bifurcation. A prolonged excitation due to this ongoing compression of the baroreceptors in the carotid sinus was assumed to have led to a cardiac arrest. In this case report, the authors discuss the underlying pathophysiology of this potentially lethal and rare reflexogenic incident also known as the Hering reflex and discuss possible therapeutic measures.

Postmortem noninvasive virtual autopsy: extrapleural hemorrhage after blunt thoracic trauma

A 19-year-old man speeding recklessly along a highway caused a left-frontal crash with another car. After his vehicle came to a standstill, he climbed out of the wreck and crawled across the tarmac to the other side of the road, where he died several minutes after the accident and before the arrival of an ambulance. Postmortem multislice computed tomography (MSCT) demonstrated fractures of the first, second, and third ribs and scapula on the left, an extrapleural hemorrhage in the apical region of the left thorax, as well as a large amount of blood in the left thoracic cavity. These radiologic findings were indicative of a delayed rupture of a traumatic extrapleural hematoma into the pleural space. A traditional autopsy confirmed the very rare diagnosis of a traumatic extrapleural hemorrhage with a delayed rupture.

Post-mortem radiological CT identification based on classical ante-mortem X-ray examinations

Radiological identification is important in forensic medicine. Identification using comparison of individualising structures with ante- and post-mortem conventional radiographs has been known for a long time. New radiological procedures such as computed tomography (CT) and magnetic resonance imaging (MRI) are being increasingly used for identification. In this paper, a new comparative approach using various radiological methods is described and its application demonstrated. This new approach is the comparison of ante-mortem conventional radiographs with projected images calculated from post-mortem CT data. The identification procedure will be illustrated with reference to the frontal sinus and the pelvis.

Application of 3D documentation and geometric reconstruction methods in traffic accident analysis: with high resolution surface scanning, radiological MSCT/MRI scanning and real data based animation

The examination of traffic accidents is daily routine in forensic medicine. An important question in the analysis of the victims of traffic accidents, for example in collisions between motor vehicles and pedestrians or cyclists, is the situation of the impact. Apart from forensic medical examinations (external examination and autopsy), three-dimensional technologies and methods are gaining importance in forensic investigations. Besides the post-mortem multi-slice computed tomography (MSCT) and magnetic resonance imaging (MRI) for the documentation and analysis of internal findings, highly precise 3D surface scanning is employed for the documentation of the external body findings and of injury-inflicting instruments. The correlation of injuries of the body to the injury-inflicting object and the accident mechanism are of great importance. The applied methods include documentation of the external and internal body and the involved vehicles and inflicting tools as well as the analysis of the acquired data. The body surface and the accident vehicles with their damages were digitized by 3D surface scanning. For the internal findings of the body, post-mortem MSCT and MRI were used. The analysis included the processing of the obtained data to 3D models, determination of the driving direction of the vehicle, correlation of injuries to the vehicle damages, geometric determination of the impact situation and evaluation of further findings of the accident. In the following article, the benefits of the 3D documentation and computer-assisted, drawn-to-scale 3D comparisons of the relevant injuries with the damages to the vehicle in the analysis of the course of accidents, especially with regard to the impact situation, are shown on two examined cases.

Effects of genetic and environmental factors on chronic lower airway disease in horses

BACKGROUND: Environment and genetics influence the manifestation of recurrent airway obstruction (RAO), but the associations of specific factors with mild, moderate, and severe clinical signs are unknown. HYPOTHESIS: We hypothesized that sire, feed, bedding, time outdoors, sex, and age are associated with clinical manifestations of mild, moderate, and severe lower airway disease. ANIMALS: Direct offspring of 2 RAO-affected Warmblood stallions (F1S1, n = 172; F1S2, n = 135); maternal half-siblings of F1S1 (mHSS1, n = 66); and an age-matched, randomly chosen control group (CG, n = 33). METHODS: A standardized questionnaire was used to assess potential risk factors and to establish a horse owner assessed respiratory signs index (HOARSI 1-4, from healthy to severe) according to clinical signs of lower airway disease. RESULTS: More F1S1 and F1S2 horses showed moderate to severe clinical signs (HOARSI 3 and HOARSI 4 combined, 29.6 and 27.3%, respectively) compared with CG and mHSS1 horses (9.1 and 6.2%, respectively; contingency table overall test, P < .001). Sire, hay feeding, and age (in decreasing order of strength) were associated with more severe clinical signs (higher HOARSI), more frequent coughing, and nasal discharge. CONCLUSIONS AND CLINICAL RELEVANCE: There is a genetic predisposition and lesser but also marked effects of hay feeding and age on the manifestation of moderate to severe clinical signs, most markedly on coughing frequency. In contrast, mild clinical signs were not associated with sire or hay feeding in our populations.

Postmortem angiography: review of former and current methods

OBJECTIVE: Postmortem investigations are becoming more and more sophisticated. CT and MRI are already being used in pathology and forensic medicine. In this context, the impact of postmortem angiography increases because of the rapid evaluation of organ-specific vascular patterns, vascular alteration under pathologic and physiologic conditions, and tissue changes induced by artificial and unnatural causes. CONCLUSION: In this article, the advantages and disadvantages of former and current techniques and contrast agents are reviewed.

Nontraumatic intracranial epidural hematoma: a case report

An outwardly mummified and inwardly badly decomposed body was found in a garage. At autopsy, no injuries were detected. Apart from coronary heart disease, with an old myocardial scar and a hepatic steatosis, the most striking finding was a large intracranial epidural hemorrhage situated at the left frontal lobe. As a relevant traumatic genesis could be ruled out, we deemed this a nontraumatic epidural hematoma. This finding is extremely rare. Several underlying disorders have been discussed as causes of spontaneous epidural hematomas. In this presented case, the authors discuss possible etiological factors.

VIRTOPSY - the Swiss virtual autopsy approach

The aim of the VIRTOPSY project () is utilizing radiological scanning to push low-tech documentation and autopsy procedures in a world of high-tech medicine in order to improve scientific value, to increase significance and quality in the forensic field. The term VIRTOPSY was created from the terms virtual and autopsy: Virtual is derived from the Latin word 'virtus', which means 'useful, efficient and good'. Autopsy is a combination of the old Greek terms 'autos' (=self) and 'opsomei' (=I will see). Thus autopsy means 'to see with ones own eyes'. Because our goal was to eliminate the subjectivity of "autos", we merged the two terms virtual and autopsy - deleting "autos" - to create VIRTOPSY. Today the project VIRTOPSY combining the research topics under one scientific umbrella, is characterized by a trans-disciplinary research approach that combines Forensic Medicine, Pathology, Radiology, Image Processing, Physics, and Biomechanics to an international scientific network. The paper will give an overview of the Virtopsy change process in forensic medicine.

Asphyxial suicide by inhalation of helium inside a plastic bag

Asphyxial suicide by placing a plastic bag over the head, especially in combination with inhalation of gases, is a rarely described method of committing suicide. This article reports a case of suicidal asphyxiation by inhaling the inert gas helium inside a plastic bag. A 64-year-old man probably followed the instructions described in an article about committing suicide written by a medical practitioner from Zürich. This form of suicide is recommended by right-to-die groups and in the internet as a certain, fast, and painless suicide method. Additionally, it leaves only seldom externally visible marks or pathomorphological findings on the body. If the plastic bag and other auxiliary means are removed by another person, the forensic death investigation of cause and manner of death may be very difficult. Therefore, the death scene investigation and the inquiry ordered in the environment of the deceased are very important.

Inhalant deaths in South Australia: a 20-year retrospective autopsy study

A 20-year retrospective study of inhalant deaths in South Australia, autopsied at Forensic Science SA, was undertaken from January 1983 to December 2002. Thirty-nine cases were identified from an autopsy pool of 18,880 cases, with a male to female ratio of 12:1. Sixty-four percent of the victims (N = 25) died during voluntary inhalation of volatile substances and 28% (N = 11) committed suicide utilizing a volatile substance or gas. The remaining 3 cases involved a workplace accident (N = 1) and 2 cases of autoerotic death where inhalants were being used to augment solitary sexual activity. The mean age of the 28 victims of accidental inhalant death of 21 years (range, 13-45 years) was considerably less than that of the 11 suicide victims of 31.5 years (range, 17-48 years). No homicides were found. Approximately one quarter of the victims were Aboriginal (N = 11), 10 of whom had died as a result of gasoline inhalation ("petrol sniffing"). Other common substances of abuse were aliphatic hydrocarbons such as butane. The study has shown that those most at risk for accidental or suicidal inhalant deaths were young males, with 92% of victims overall being male, and with 77% of victims being under 31 years of age. Gasoline inhalation remains a significant problem in Aboriginal communities in South Australia.