Glucocorticoids protect renal mesangial cells from apoptosis by increasing cellular sphingosine-1-phosphate

Neutral ceramidase (NCDase) and sphingosine kinases (SphKs) are key enzymes regulating cellular sphingosine-1-phosphate (S1P) levels. In this study we found that stress factor-induced apoptosis of rat renal mesangial cells was significantly reduced by dexamethasone treatment. Concomitantly, dexamethasone increased cellular S1P levels, suggesting an activation of sphingolipid-metabolizing enzymes. The cell-protective effect of glucocorticoids was reversed by a SphK inhibitor, was completely absent in SphK1-deficient cells, and was associated with upregulated mRNA and protein expression of NCDase and SphK1. Additionally, in vivo experiments in mice showed that dexamethasone also upregulated SphK1 mRNA and activity, and NCDase protein expression in the kidney. Fragments (2285, 1724, and 1126 bp) of the rat NCDase promoter linked to a luciferase reporter were transfected into rat kidney fibroblasts and mesangial cells. There was enhanced NCDase promoter activity upon glucocorticoids treatment that was abolished by the glucocorticoid receptor antagonist RU-486. Single and double mutations of the two putative glucocorticoid response element sites within the promoter reduced the dexamethasone effect, suggesting that both glucocorticoid response elements are functionally active and required for induction. Our study shows that glucocorticoids exert a protective effect on stress-induced mesangial cell apoptosis in vitro and in vivo by upregulating NCDase and SphK1 expression and activity, resulting in enhanced levels of the protective lipid second messenger S1P.

Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer

Procalcitonin has been well established as an important marker of sepsis and systemic infection. The authors evaluated the diagnostic and predictive value of calcitonin and its prohormone procalcitonin in medullary thyroid cancer.

Virtopsy: CT and MR imaging of a fatal head injury caused by a hatchet: A case report

Hatchet blows to the human skull often cause fatal injuries. We present a case of homicide by hatchet blow that underwent CT, MRI, and autopsy examination. Skull fragmentation, fracture lines, and brain injuries were demonstrated prior to autopsy. Many of the hatchet-specific characteristics (flaking, crushing, shattering, and fracture lines) described in literature were observed in the post-mortem imaging of this case.

Suicidal knife wound to the heart: challenges in reconstructing wound channels with post mortem CT and CT-angiography

We present a case of an individual who stabbed himself through the heart with a large knife. Post mortem computed tomography (CT) and CT-angiography were used to assess the stab channel and to reconstruct the sequence of events. After penetrating injuries to the chest, both the intra-thoracic organs and the injury causing instrument may shift (e.g. from pnemothorax) and render forensic reconstructions more challenging. This case report illustrates the potentials and the pitfalls of CT for the reconstruction of penetrating injures to the chest.

A new approach in virtopsy: Postmortem ventilation in multislice computed tomography

Although postmortem imaging has gained prominence in the field of forensic medicine, evaluation of the postmortem lung remains problematic. Specifically, differentiation of normal postmortem changes and pathological pulmonary changes is challenging and at times impossible. In this study, five corpses were ventilated using a mechanical ventilator with a pressure of 40 mbar (40.8 cm H(2)O). The ventilation was performed via an endotracheal tube, a larynx mask or a continuous positive airway pressure mask. Postmortem computed tomographic images of the lungs before and with a ventilation of 40 mbar (40.8 cm H(2)O) were evaluated and the lung volumes were measured with segmentation software. Postmortem ventilation led to a clearly visible decrease of both the density in the dependant parts of the lungs and ground glass attenuation, whereas consolidated areas remained unchanged. Furthermore, a mean increase in the lung volume of 2.10 l was seen. Pathological changes such as septal thickening or pulmonary nodules in the lung parenchyma became more detectable with postmortem ventilation. Intracorporal postmortem mechanical ventilation of the lungs appears to be an effective method for enhancing detection of small pathologies of the lung parenchyma as well as for discriminating between consolidation, ground glass attenuation and position-dependent density.

Fatal thoracic impalement on postmortem imaging

In the present paper, the authors describe a case of fatal thoracic impalement in a victim of a road traffic accident, by penetration of a metal handrail. The driver lost control of his car while overtaking three cars. Due to the force of the vehicle collision with a metal railing, the upper cross bar penetrated the front of the car and subsequently the driver was pierced by the center-pillar in the car. Death occurred at the scene of the accident. Postmortem, computed tomography, computed tomography angiography and a magnetic resonance tomography were performed and revealed severe heart destruction and hemorrhage as cause of death. The present case report shows that postmortem imaging might have value as a screening method to decide whether arising forensic questions can be answered just by imaging like in the presented case or if further examinations such as conventional autopsy are required.

[Examination results and autopsy findings in assaults on elderly people]

As the percentage of elderly people in the population grows, violence against persons of advanced age constitutes an increasing social problem. The findings of the clinical forensic examinations (CE group) and autopsies performed on elderly violence victims (> or = 60 years) between 1999 and 2008 at the Institute of Legal Medicine of the Hanover Medical School were retrospectively analysed. In all, the study material comprised 55 victims of the CE group (35 females and 20 males, median age 73.5 years) and 55 autopsies (33 females and 22 males, median age 72.7 years). In most of the autopsy cases, the suspect was a family member or partner. In contrast, the alleged perpetrator was a stranger in most cases of the CE group. Blunt force injuries were most often found in the CE group victims (63.6%). Altogether, 38.2% (CE group) and 20.0% (autopsy cases) of the violent assaults were associated with robbery. In the majority of the CE cases, the victims suffered potentially or acute life-threatening injuries. In summary, the analysis shows that elderly people frequently become victims of robbery and blunt force injury. In most homicides of old people, the perpetrator is familiar to the victim. In surviving elderly violence victims, the assault is more likely to be reported to the police if the suspect is a stranger.

[Examination reports on survived strangulation cases]

Clinical-forensic examination of strangulation victims is an increasing part of the routine of many forensic pathology institutes. The cases examined between 2004 and 2008 at the Institute of Legal Medicine of the Hanover Medical School were retrospectively analysed. In total, the study material comprised 218 victims (175 females and 43 males). In 80.7 %, the clinical-forensic examination was performed within 24 hours after the incident. In the overwhelming number of cases, the alleged perpetrator was no stranger. 128 victims (58.7 %) had strangulation marks, 32 victims (14.7 %) ligature marks and 65 victims (29.8 %) nail marks. Four victims showed injuries of the laryngeal and pharyngeal structures (reddening, hematomas, swelling and in one case a fracture of the cricoid cartilage on both sides). Extensive petechiae were predominantly seen in the conjunctivae, the buccal mucosa and the skin of the face in cases where the victims suffered a loss of consciousness. 87 cases (39.9% were classified as potentially life-threatening and 30 cases (13.8 %) as acute life-threatening events. This classification is of legal relevance for the penalty. In addition, 60 victims experienced sexual violence. These results suggest that early clinical-forensic examination is crucial for documenting forensic evidence in support of police investigations and may deliver significant details relevant in court.

[Homicide by bow and arrow]

Since the invention of firearms, arrow wounds represent a rarity in the daily routine of forensic pathologists. In the present paper, we describe a homicide by a broadhead arrow shot from a compound bow in a domestic environment. Based on this homicide, we discuss the characteristics of the lesion caused by broadhead arrows and field-tip arrows. We look critically at the free saleability of this equipment mostly used for sport shooting in Germany.

Planned complex suicide: Self-strangulation and plaster ingestion

The literature contains many case reports of planned and complex suicides, which combine various methods to commit suicide. In this article, we present the anomalous suicide of an adult male by strangulation with a belt and simultaneous ingestion of plaster. The specific circumstances of the case are described and relevant literature is briefly reviewed. This case vignette illustrates one example of the wide ranging methods employed in suicides and may represent the first reported case of a fatal complex suicide involving self-strangulation and plaster ingestion. Knowledge of varied and sometimes unusual suicide methods is important to the forensic investigator to prevent unnecessary criminal investigation and to reliably and confidently establish manner and cause of death.

[Analysis of clinical forensic examination reports on sexually abused children]

Clinical forensic examinations of children suspected of having been sexually abused are increasingly part of the routine of medicolegal institutes. The findings collected from 2005 until 2007 at the Institute of Legal Medicine of the Hanover Medical School were analysed retrospectively. Altogether, 91 children (74 females, 17 males, mean age 8.7 years) were examined. In 87.9% of the cases, the examination had been ordered by the police. In 73.6%, the victim knew the suspected perpetrator well or he was a family member. 40.7% of the children were seen within 72 hours after the alleged abuse. 12.1% of the children had extragenital lesions. In 27% of the victims, marked anogenital injuries were found, which were characteristic of sexual abuse in 9%. In 18 cases (20.2%), swabs were taken for spermatozoa detection. 3 of 17 vaginal smears showed positive test results for sperm up to 21 hours after the incident. No spermatozoa could be detected in 4 anal and 2 oral swabs as well as in one swab taken from the skin of the victim's thigh. In summary, the evaluation shows that early clinical forensic examination of children suspected of having been sexually abused is crucial to document evidence that is highly significant for the investigation and court proceedings. Often suspected sexual child abuse cannot be proved by medical findings alone. Of course, the absence of anogenital injuries does nor rule out sexual abuse.

Analysis of clinical forensic examination reports on sexual assault

Medical-forensic examination of sexual assault victims and alleged offenders is a common task of many forensic institutes. In the current study, the results from samples taken at the Institute of Legal Medicine, Hanover Medical School, during a period from 2005 to 2007 were retrospectively evaluated. In total, 292 victims (283 females and nine males) and 88 suspects were examined. At the time of the assault, 41.8% of the victims and 43.2% of the alleged perpetrators were under the influence of alcohol. Injuries were found in 84.9% of the victims and 39.8% of the suspects. Thirty victims (10.3%) reported having been choked or strangled. Cytology was performed in 218 victims. In 81 cases (38.0%), sperm could be detected in vaginal swabs up to 3 days post-assault. In seven (18.9%) out of 37 anal samples, evidence of sperm could be found 24 h post-assault. None of 22 oral samples was positive for sperm. Out of 301 sexual assault cases, 171 could be proved by means of medical-forensic examination. In summary, our evaluation shows that an early medical-forensic examination of both victim and suspect can secure numerous medical findings. Furthermore, persons intoxicated by alcohol, handicapped persons and persons with psychiatric disorders are more vulnerable to become a sexual assault victim.

Blood aspiration as a vital sign detected by postmortem computed tomography imaging

Blood aspiration is a significant forensic finding. In this study, we examined the value of postmortem computed tomography (CT) imaging in evaluating findings of blood aspiration. We selected 37 cases with autopsy evidence of blood in the lungs and/or in the airways previously submitted to total-body CT scanning. The CT-images were retrospectively analyzed. In one case with pulmonary blood aspiration, biopsy specimens were obtained under CT guide for histological examination. In six cases, CT detected pulmonary abnormalities suggestive of blood aspiration, not mentioned in the autopsy reports. CT reconstructions provided additional data about the distribution and extent of aspiration. In one needle-biopsied case, the pulmonary specimens showed blood in the alveoli. We suggest the use of CT imaging as a tool complementary to traditional techniques in cases of blood aspiration to avoid misdiagnosis, to guide the investigation of lung tissue, and to allow for more evidence-based inferences on the cause of death.

Phylogenetic approach reveals that virus genotype largely determines HIV set-point viral load

HIV virulence, i.e. the time of progression to AIDS, varies greatly among patients. As for other rapidly evolving pathogens of humans, it is difficult to know if this variance is controlled by the genotype of the host or that of the virus because the transmission chain is usually unknown. We apply the phylogenetic comparative approach (PCA) to estimate the heritability of a trait from one infection to the next, which indicates the control of the virus genotype over this trait. The idea is to use viral RNA sequences obtained from patients infected by HIV-1 subtype B to build a phylogeny, which approximately reflects the transmission chain. Heritability is measured statistically as the propensity for patients close in the phylogeny to exhibit similar infection trait values. The approach reveals that up to half of the variance in set-point viral load, a trait associated with virulence, can be heritable. Our estimate is significant and robust to noise in the phylogeny. We also check for the consistency of our approach by showing that a trait related to drug resistance is almost entirely heritable. Finally, we show the importance of taking into account the transmission chain when estimating correlations between infection traits. The fact that HIV virulence is, at least partially, heritable from one infection to the next has clinical and epidemiological implications. The difference between earlier studies and ours comes from the quality of our dataset and from the power of the PCA, which can be applied to large datasets and accounts for within-host evolution. The PCA opens new perspectives for approaches linking clinical data and evolutionary biology because it can be extended to study other traits or other infectious diseases.