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Sudden cardiac death in a young woman: tumor of the atrioventricular (AV) node or citalopram intoxication?

Atrioventricular (AV) node tumor is a very rare lesion of the cardiac conduction system. Clinically, it is associated with complete AV block and sudden cardiac death, often in apparently healthy young people. We report a case of a 24-year-old woman who developed ventricular fibrillation during sexual intercourse and died before admittance to the hospital. The woman had a medical history of depression and was treated with citalopram.At first, no macroscopic or microscopic pathologic changes were found. Toxicologic analysis showed a toxic level of citalopram in the blood. Further microscopic examination of the cardiac conduction system disclosed a tumor of the AV node. Immunohistochemical staining confirmed endodermal origin in accordance with the latest hypothesis of the pathogenesis of this tumor. It was concluded that this young woman died of cardiac arrhythmia due to the AV tumor and not from citalopram intoxication, as first suspected. This case emphasizes the importance of a microscopic examination of the cardiac conduction system in cases of sudden unexpected death, even in cases with a plausible cause and manner of death at first glance.

Adult↗

Dehydration and heat-related death: sweat lodge syndrome.

A 37-year-old Caucasian male died of dehydration and heat exposure following a sweat lodge ceremony in outback Australia. The case demonstrates difficulties that may arise in the determination of the cause of death at autopsy due to nonspecific pathologic findings in hyperthermic deaths. There are also a number of features that characterize this particular "sweat lodge syndrome," including prolonged exposure to elevated temperatures in a relatively uncontrolled environment, failure to ensure adequate hydration, failure to appreciate the significance of loss of consciousness, use of ineffective alternative methods of treatment, and delay in seeking appropriate medical care. Unfortunately, the adoption of rituals and practice from other cultures may not be a completely safe undertaking. Participants in this type of activity must be cognizant of the types of medical problems that may arise. Individuals with significant cardiovascular disease, those who are taking certain medications that predispose to hyperthermia, or those who have had large amounts of alcohol should not enter sweat lodges.

Adult↗

Long-term intracerebral inflammatory response after traumatic brain injury.

Epidemiological and pathological studies suggest that head injury is a significant risk factor for subsequent neurodegeneration and cognitive decline in later life. The precise mechanisms for the development of post-traumatic neurodegenerative change are unclear but we hypothesize that persistence of inflammatory processes in the brain may play a key role and that some individuals are more susceptible to such changes based on their genetic make-up. In support of this hypothesis we present evidence of persistent elevated microglial activity in long-term survivors of head injury and the suggestion of an association between the extent of this activity and interleukin-1 genotype.

Adolescent↗

Pancreatic changes in cases of death due to hypothermia.

Several morphological alterations of the pancreatic tissue have been described as common findings in hypothermia (e.g. bleedings, pancreatitis, vacuoles). The frequency of these findings varies a lot. It was the aim of this study to clarify the kind and frequency of pancreatic changes in cases of death due to hypothermia. The autopsy reports of 143 cases of fatal hypothermia were, retrospectively, evaluated with regard to describe macroscopic findings in the pancreas. Additionally, microscopic investigations of tissue samples of the pancreas were carried out in 62 cases. As a control group, pancreatic samples of 25 autopsy cases without hypothermia and without alcoholism were collected. Additionally, pancreatic samples of 25 further autopsy cases with an alcoholic disease in the case history were investigated. In only 5 out of 143 cases of the study group, macroscopic bleedings in the pancreas were described. One case of acute and one of chronic pancreatitis was found in the autopsy reports. In 11 (17.7%) out of 62 cases, microscopic investigations yielded bleedings in the pancreatic tissue and in 24 (38.7%) out of 62 cases, optically empty vacuoles in the adenoid cells were found. In 15 out of 62 cases (24.2%), autolysis was too pronounced to gain utilisable results. In the control group without alcoholism, 12 out of 25 cases (48%) were diagnosed without pathological findings, five cases showed bleedings, one case an acute pancreatitis, one case a chronic pancreatitis and in six cases, the pancreatic tissue was autolytic. Vacuoles in the adenoid cells were not found. In the additional collective with alcoholism in the case history, 13 cases presented signs of an acute or a chronic pancreatitis. In 3 out of these 13 cases, vacuoles in the adenoid cells were found, but no case with vacuoles and without signs of a chronic pancreatitis was observed. The high frequency of pancreatic bleedings in cases of fatal hypothermia as described in the literature cannot be confirmed by our investigations. Only the vacuoles in the adenoid cells of the pancreas seem to be an additional sign of death due to hypothermia or associated with hypothermia.

Adenoids↗

High thyroglobulin (Tg) concentrations in fatal traumatic brain injuries.

It is well known that under physiological conditions, the Tg molecule is the substrate for the hormones triiodothyronine and thyroxine. Its function outside the thyroid gland is unknown. Under certain pathologic conditions, an increase in Tg concentrations in the blood can occur, a phenomenon that is used in the clinical diagnosis of certain thyroid disorders. However, fatal traumatic brain injuries (TBI) can also produce a raised Tg concentration in blood. In such cases, mean (n=151) Tg concentrations of 405.8+/-353.3 ng/mL have been observed, with the values in 57% of these cases exceeding 200 ng/mL. Since it was possible to rule out specifically any thyroid disorders in these cases, the raised values may be explained by the effect of TSH in the spectrum of the "hypothalamic-pituitary-thyroid axis." This assumption has been substantiated by immunohistochemical tests for TSH and Tg. Compared with the controls (sudden unnatural deaths: Tg 23.3+/-27.6 ng/mL), the raised Tg values in the TBI cases were usually accompanied by a reduction in the intensity of immunohistochemical reactions relating to TSH and Tg. The hypophysis showed evidence of significant damage with morphologic changes such as edema, hemorrhages, and focal necrosis in association with reduced TSH levels.

Adolescent↗

Comparison between computed tomography (CT) and autopsy findings in cases of abdominal injury and disease.

We report 10 autopsy cases involving fatal pathological changes in abdominal organs, for which findings of computed tomography (CT) on admission or after death were compared with autopsy findings. Two of the cases were death due to natural causes and eight were death due to traffic accidents. From the findings at autopsy, the causes of death were considered to be rupture of an aortic aneurysm in one case, gastrointestinal bleeding due to gastric cancer in one case, retroperitoneal bleeding in two cases, laceration of the liver in three cases, and traumatic rupture of the small intestine in three cases. CT findings revealed ascites or retroperitoneal bleeding in eight cases. However, in the cases of small-intestinal rupture, CT findings on admission revealed no free air. Therefore, ascites on CT should be regarded as a useful indicator of blunt abdominal trauma. Hepatic portal venous gas, known to be a post-mortem change, was significantly evident on post-mortem CT in cases of traumatic liver or intestinal injury, and was also seen in cases where the period between the accident and CT examination was long.

Accidents, Traffic↗

Immunohistochemical investigation of ubiquitin and myoglobin in the kidney in medicolegal autopsy cases.

We examined the immunohistochemical distributions of ubiquitin (Ub) and myoglobin (Mb) in human kidney tissues to assist the pathological assessment of death due to trauma. Medicolegal autopsy cases at our institute (n=138: 0-96 years of age, 105 males and 33 females) were examined. Causes of death were blunt injury (n=31), sharp injury (n=15), poisoning (n=11), drowning (n=10), fire fatalities (n=25), hypothermia (n=7), asphyxiation (n=14), hyperthermia (n=3), and natural diseases (n=22) for controls. Immunostaining of Ub and Mb was performed on the formalin-fixed paraffin-embedded kidney tissue sections. Quantitative analyses by estimating the proportion of Ub- and Mb-positive cells (%positivity) of renal tubule epithelial cells showed that the positivities for Ub and Mb were higher in subjects who died due to fire, blunt injury, sharp injury and fatal hypothermia than in other groups. The Ub-positivity correlated with the severity of airway thermal injury in fire deaths, survival time in blunt injury, and serum markers for renal failure in deaths due to sharp injury. Concomitant increases in the tubular Mb- and Ub-positivities were characteristic to deaths from injury and hypothermia. These findings suggest that Ub may serve as a sensitive indicator of the fatal influence of traumas.

Adolescent↗

Quantitative RT-PCR assays of hypoxia-inducible factor-1alpha, erythropoietin and vascular endothelial growth factor mRNA transcripts in the kidneys with regard to the cause of death in medicolegal autopsy.

Accumulating studies demonstrate that the expressions of hypoxia-inducible factor 1 (HIF-1), erythropoietin (EPO) and vascular endothelial growth factor (VEGF) depend on cellular oxygen tension, which is involved in the pathological process of tissue hypoxia and/or ischemia. The present study investigated hypoxia-inducible factor-1alpha (HIF-1alpha), EPO and VEGF mRNA expressions in the kidney with regard to the cause of death in medicolegal autopsy. Relative quantifications of HIF-1alpha, EPO and VEGF mRNAs, based on real-time TaqMan reverse transcription-polymerase chain reaction (RT-PCR), were performed on tissue specimens obtained from consistent sites of the bilateral renal cortices. The cases (total, n=245, 6-48h postmortem) included fatal blunt/sharp instrument injuries (n=53/31), asphyxia (n=28: aspiration, n=8; strangulation/hanging, n=20), drowning (n=27), fire fatality (n=62), acute myocardial infarction/ischemia (AMI, n=39), and gastrointestinal hemorrhage (n=5). Both HIF-1alpha and EPO mRNA levels were significantly lower in drowning cases. More characteristic findings were found for VEGF mRNA: it showed higher expression levels for AMI, acute blunt/sharp instrument injury, and aspiration, whereas it was lower for neck compression (strangulation/hanging), drowning, fire fatality with higher blood carboxyhemoglobin (COHb) levels (>60%), peracute blunt injury, and gastrointestinal hemorrhage. Quantitative assays of renal HIF-1alpha, EPO and VEGF mRNA transcripts are potentially useful for investigating the pathophysiology of death, and VEGF mRNA may be especially useful as an indication of acute circulatory failure.

Adolescent↗

Pathology of peliosis.

Peliosis is a pathological entity characterized by the gross appearance of multiple cyst-like, blood-filled cavities within parenchymatous organs. Peliosis has been related to several underlying debilitating illnesses such as tuberculosis, hematological malignancies, the acquired immunodeficiency syndrome (AIDS), and post-transplant immunodeficiency, as well as intravenous drug abuse, chronic alcoholism, and in conjunction with the intake of oral contraceptives or steroids. The classical pathoanatomical concept is based upon the opinion that peliosis exclusively develops in organs belonging to the mononuclear phagocytic system (liver, spleen, bone marrow, and lymph nodes). However, a paucity of studies indicates that other organs such as lungs, parathyroid glands, and kidneys may be affected too. Concerning the underlying pathogenetic mechanisms of onset and maintenance of peliosis, the morphological data obtained by different investigators suggest that there is more than one path of formal pathogenesis (e.g., congenital malformation of vessels manifesting under altered local intravascular pressure conditions, acquired vascular disorder triggered by toxic noxae, active proliferation of vessels corresponding to the benign end on the spectrum of neoplastic vascular lesions). In the liver, at gross inspection, the peliotic lesions give the cut sections a "swiss cheese" appearance. Microscopically, two different types of peliosis can be distinguished in the liver: (1) "parenchymal peliosis" consisting of irregular cavities that are neither lined by sinusoidal cells nor by fibrous tissue, and (2) "phlebectatic peliosis" characterized by regular, spherical cavities lined by endothelium and/or fibrosis. One of the differential diagnoses that most closely resembles peliosis hepatis is secondary hepatic congestion due to veno-occlusive disease or the Budd-Chiari syndrome. In the spleen, the peliotic lesions may be arranged sporadically, disseminated, or in clusters in an uneven distribution pattern. Histologically, the cavities show frequently well-demarcated margins that may appear focally lined by sinusoidal endothelium, or totally lack a clear cell lining. Differential diagnoses are hemangiomas and involvement of the spleen in hairy-cell leukaemia. Since the disease may culminate in spontaneous rupture of the affected organ and thus may mimic a violent death at autopsy, peliosis is far more than just another morphological curiosity. Awareness of peliosis at autopsy as well as an appreciation for the histopathological changes in less characteristic or advanced cases may become an important issue for both the forensic and clinical pathologist.

Bone Marrow Diseases↗

Quantitative morphometry of granular 'dot-like' ubiquitin-immunoreactivity in the crus cerebri in asphyxiation and fire fatalities.

In the central nervous system (CNS), a variety of ubiquitinated structures have been reported, usually as pathological alterations of the brain related to degenerative diseases or aging. However, previous studies showed an increase in the ubiquitin (Ub)-immunoreactive intranuclear inclusion of the pigmented neurons of the substantia nigra in the midbrain in asphyxiation and fire fatalities in the adult subjects. The aim of the present study was to examine granular 'dot-like' Ub-immunoreactivity in the crus cerebri (cortico-spinal tracts) in related fatalities (over 35 years of age, n=169), including fatal asphyxiation (n=27), drownings (n=14), fire fatalities (n=60), and control groups (n=68). Dot-like Ub-immunoreactivity was clearly observed in the descending tract of the crus cerebri. Morphometric analysis of the positive granular area (dot-like Ub-area) showed a higher value in strangulation and fire fatalities and a lower value in hemorrhagic and head injury deaths, as was observed for the inclusion-type neuronal Ub-positivity. However, there was a difference between those markers: a low value was seen for the inclusion-type neuronal Ub-positivity in hanging and drownings, and a difference in the dot-like Ub-area was detected between fire fatalities with lower and higher COHb levels. Our findings suggested the possible usefulness of these markers for examination of CNS stress responses in traumas, at least in middle-aged and elderly victims and a partial difference in stress reaction between the cortico-spinal tracts and dopaminergic neurons.

Adult↗

[The role of Pathology Department of the I.M. Sechenov Moscow Medical Academy in the development of forensic medicine].

The chair of pathology has greatly contributed to establishment and development of prosector's speciality: training of pathologists, initiation of first clinico-anatomical conferences and their upgrading, introduction of novel morphological techniques and other advanced methods, publication of books, guidelines, manuals. The chair, A. I. Abrikosov and I. V. Davydovsky especially, contributed much to transformation of the pathology service in Russia after 1917.

Forensic Medicine↗

Forensic visualization of foreign matter in human tissue by near-infrared spectral imaging: methodology and data mining strategies.

BACKGROUND: Rapidity of data acquisition, high image fidelity and large field of view are of tremendous value when looking for chemical contaminants or for the proverbial "needle in the haystack" - in this case foreign inclusions in histologic sections of biopsy or autopsy tissues. Near infrared chemical imaging is one of three chemical imaging techniques (NIR, MIR and Raman) based on vibrational spectroscopy, and provides distinct technical advantages for this application. METHODS: We have chosen to utilize and evaluate near infrared (NIR) imaging for studies of foreign materials in tissue because the experimental configuration is relatively simple, data collection is rapid, and large sample areas can be screened with high image fidelity and spatial resolution. RESULTS: We have shown that NIR imaging can readily find and identify silicone gel inclusions in biological tissue samples. Additionally, preliminary results indicate that spectral signatures in the data set are also potentially sensitive to structural changes in the surrounding tissue that may be induced by the foreign body. CONCLUSIONS: NIR chemical imaging is a powerful, non-destructive tool for localization and identifying foreign contaminants in biological tissue. Preliminary results indicate that NIR imaging is also sensitive enough to differentiate tissue types (perhaps based on collagen structural differences), and provide data on the spatial localization of these components.

Animals↗

Magnetic resonance imaging and mathematical modeling of progressive formalin fixation of the human brain.

The temporal magnetic resonance (MR) appearance of human brain tissue during formalin fixation was measured and modeled using a diffusion mathematical model of formalin fixation. Coronal MR images of three human brains before formalin fixation and at multiple time points thereafter were acquired. T1 relaxation, T2 relaxation, water apparent diffusion coefficient (ADC), and proton density (PD) maps were calculated. The size of a light "formalin band" region, visible in T1 weighted images, was compared to a mathematical model of diffusive mass transfer of formalin into the brain. T1 relaxation, T2 relaxation, and PD all decreased, in both gray and white matter, as formalin fixation progressed. The ADC remained more or less constant. The location of the inner boundary of the formalin band followed a time course consistent with the steepest formalin concentration gradient in the mathematical model. Based on the diffusion model, the brain is not completely saturated in formalin until after 14.8 weeks of formalin immersion and, based on the observed changes in T1, T2, and PD, fixation is not complete until after 5.4 weeks. During fixation, the ongoing attenuation of T1 relaxation, T2 relaxation, and PD must be taken into consideration when performing postmortem MRI studies.

Brain↗

An original technique for histological study of the human temporal bone.

An original technique for histological study of the human temporal bone is presented. It allows faster and better results than previous methods. It becomes obvious that the systematic study of the temporal bone may give important data in the field of pathology, foeto-pathology and forensic medicine.

Adult↗

Correlative analysis on the relationship between PMI and DNA degradation of cell nucleus in human different tissues.

To determining the postmortem interval (PMI) through quantitative analysis of the DNA degradation of cell nucleus in human brain and spleen by using image analysis technique (IAT). The brain and spleen tissues from 32 cadavers with known PMI were collected, subjected to cell smear every 1 h within the first 5-36 h after death, stained by Feulgen-Van's staining, Three indices reflecting DNA in brain cells (astrocytes) and splenic lymphocytes, including integral optical density (IOD), average optical density (AOD), average gray (AG) were measured by employing the mage analysis instrument. The results showed that IOD and AOD declined and AG increased with the prolongation of dead time within 5-36 h. A correlation between the PMI and gray parameters (IOD, AOD and AG) was identified and the corresponding regression equation was obtained. The parameters (IOD, AOD and AG) were proved to be effective quantitative indicators for accurate estimation of PMI within 5-36 h after death.

Cell Nucleus↗

Studies on mRNA expression of tissue-type plasminogen activator in bruises for wound age estimation.

We investigated mRNA expression of tissue-type plasminogen activator (tPA) and inflammatory cell dynamics for wound age estimation of bruises in mice. Neutrophils were detected from 1 h post-injury. Up to 8 h, they accumulated in subcutaneous tissue and the lower part of the dermis, and thereafter they extended to all the layers. Macrophages became detectable 3 h post-injury, and moderate infiltration of lymphocytes was seen from 144 h. In addition, epidermal thickening was also seen from 72 h. tPA mRNA expression peaked at 1 h, and increased slightly at 72 h post-injury. tPA mRNA was detected in epidermal cells, fibroblasts, and endothelial cells before and after injury, from 3 h in neutrophils and from 72 h in macrophages, respectively. This study presents the time-dependent expression of tPA mRNA in bruises in relation to temporal histologic characteristics during wound healing, which was considered to be useful for wound age estimation. Furthermore, it is suggested that tPA plays an important role in the first step of tissue remodeling.

Animals↗

Forensic application of VEGF expression to skin wound age determination.

An immunohistochemical study combined with morphometry was carried out to examine the time-dependent expression of vascular endothelial growth factor (VEGF) using 53 human skin wounds with different wound ages (groups I: 0-12 h, II: 1-4 days, III: 7-14 days and IV: 17-21 days). In the human wound specimens aged 4-12 h, neutrophils recruited at the wound showed no positive signals for VEGF. With an increase in wound ages of > or =7 days, granulation tissue and angiogenesis were observed, with the migration of macrophages and fibroblasts of which the cytoplasm expressed VEGF-positive reactions. Morphometrically, the average VEGF-positive ratio was highest in group III, followed by that of group IV. In groups III and IV, 13 out of 26 wound samples had VEGF-positive ratios of more than 50%. However, all of the wound samples in groups I and II showed VEGF-positive ratios of less than 50%. With regard to the practical applicability and forensic validity, these observations suggest that a VEGF-positive ratio of more than 50% possibly indicates a wound age of 7 days or more.

Adolescent↗

Cuts to the offender's own hand--unintentional self-infliction in the course of knife attacks.

In a knife attack the perpetrator can unintentionally injure his own hand, if the knife does not have an adequate handguard and the tip of the blade hits a solid, mostly bony structure while being violently thrust into the victim's body. The injuries occurring under these conditions are localized on the flexor side of the knife-holding hand and may include the index, middle, ring and little fingers. They are seen particularly often on the little finger at the level of the proximal phalanx and in the skin fold of the proximal interphalangeal joint. The majority of these cuts run transversely to the longitudinal axis of the fingers and can show a step-like arrangement with different distances to the metacarpophalangeal joints, often from ulnar-proximal to radial-distal. In the six cases presented the injuries were most pronounced on the ulnar side of the hand. When the flexor tendons of the fingers are also severed and the tendon stumps are strongly retracted this indicates that the fist was firmly closed at the time of the injury.

Adolescent↗