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M Tsokos

Publications and source records attributed to M Tsokos.

At least 19 recordsLinked to original sources
PubMed2006

Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia.

We identified four unrelated patients (three female, one male) aged 20 to 30 years with hypomyelination, pituitary hypogonadotropic hypogonadism, and hypodontia. Electron microscopy and myelin protein immunohistochemistry of sural nerves showed granular debris-lined clefts, expanded abaxonal space, outpocketing with vacuolar disruption, and loss of normal myelin periodicity. Reduced galactocerebroside, sphingomyelin, and GM1-N-acetylglucosamine and increased esterified cholesterol were found. This is a clinically homogeneous progressive hypomyelinating disorder. The term 4H syndrome is suggested.

Adult↗
PubMed2006

Evolution of VHL tumourigenesis in nerve root tissue.

Haemangioblastomas are the key central nervous system manifestation of von Hippel-Lindau (VHL) disease, which is caused by germline mutation of the VHL gene. We have recently shown that 'tumour-free' spinal cord from patients with VHL disease contains microscopic, poorly differentiated cellular aggregates in nerve root tissue, which we descriptively designated 'mesenchymal tumourlets'. Here we have investigated spinal cord tissue affected by multiple tumours. We show that a small subset of mesenchymal tumourlets extends beyond the nerve root to form proliferative VHL-deficient mesenchyme and frank haemangioblastoma. We thus demonstrate that tumourlets present potential, but true precursor material for haemangioblastoma. We further show that intraradicular tumourlets consist of scattered VHL-deficient cells with activation of HIF-2alpha and HIF-dependent target proteins including CAIX and VEGF, and are associated with an extensive angiogenic response. In contrast, activation of HIF-1alpha was only observed in the later stages of tumour progression. In addition, ultrastructural examination reveals gradual transition from poorly differentiated VHL-deficient cells into vacuolated cells with a 'stromal' cell phenotype. The evolution of frank haemangioblastoma seems to involve multiple steps from a large pool of precursor lesions.

Basic Helix-Loop-Helix Proteins↗
PubMed2006

[Atrial myocardial perforation due to catheter ablation of the cavotricuspid isthmus].

A 79-year-old man died 3.5 hours after catheter ablation of atrial fibrillation due to pericardial tamponade. Autopsy and consecutive microscopic examinations furnished evidence of electrothermical necroses topographically arranged regularly adjacent to the pulmonary veins in the left atrium and across the area of the isthmus in the right atrium with a rupture of the right atrial wall in the area of a coagulation spot. The post-mortem findings and pathogenetic considerations for the delayed pericardial tamponade are discussed.

Aged↗
PubMed2006

[Spontaneous ruptures of the urinary bladder in the routine forensic examination].

This article analyses three cases of death following a spontaneous rupture of the urinary bladder. One case is based on an extensive tamponade of the bladder eight days after a transurethral resection of the prostate gland. Two other cases of death by spontaneous rupture resulted from increased alcohol consumption. The paper presents an overview of pathomorphological findings such as the typical intraperitoneal rupture localisation at the posterior wall of the urinary bladder or bladder dome and the subsequent diagnosed causes of death. In addition predisposing (anamnestic) influencing factors such as chronic alcoholism are highlighted and their relevance for the clinical urologist and the forensic pathologist are discussed.

Adult↗
PubMed2005

Can post-mortem blood be used for DNA profiling after peri-mortem blood transfusion?

The question of whether blood transfusions can affect DNA profiling is still a contentious issue throughout the forensic community. It is hypothesised that donor leucocytes present in the administered blood will be detected upon examination of recipient blood. In order to resolve this issue, a selection of theoretical experiments were carried out to determine how much donor DNA must be present for its detection in blood components. Five casework examples of material collected from individuals after massive transfusion, including a case of whole organ transplantation, were also investigated. The results indicated that filtration processes used during blood production do not allow the passage of enough donor leucocytes for detection using current forensic profiling techniques. No evidence of secondary profile alleles were found in any case, indicating that peri-mortem blood transfusion does not affect DNA profiling.

Autopsy↗
PubMed2005

Immunohistochemical detection of hemoglobin in frost erythema.

Reddish discoloration of exposed skin areas, called frost erythema, is an important criterion for the diagnosis of fatal hypothermia. In the present study, we used immunohistochemistry in a prospective trial to show that on the molecular level, the correlate of frost erythema is hemoglobin without hemorrhage. Furthermore, we compared routine histological and immunohistochemical features of frost erythema, hematoma and livor mortis and established some criteria for their histological differentiation.

Aged↗
PubMed2005

Black oesophagus: a rare disorder with potentially fatal outcome. A forensic pathological approach based on five autopsy cases.

Black oesophagus is a rare pathological condition of unknown aetiology characterised by a full length, circumferential black discolouration of the entire oesophageal mucosa. The disease is sporadically encountered during upper gastrointestinal endoscopy. We used conventional histology, enzyme histochemistry and immunohistology to examine five autopsy cases (four males, one female; age range 43-86 years) of black oesophagus. On microscopical examination, the esophageal mucosa was entirely necrotic with demarcation by a leukocytic infiltrate in the upper submucosa. This infiltrate was dominated by neutrophilic granulocytes and scattered macrophages lacking haemosiderin deposits, placing the noxious mucosal injury in a time frame of approximately 24-72 h prior to death. Black oesophagus was established as the immediate cause of death in one case due to desanguination from the oesophagus and significantly contributed to the fatal outcome in a second case. Apart from a history of chronic alcohol consumption in four cases, no other pre-existing pathological or debilitating conditions could be established. The remarkably consistent pathomorphological picture of the disease seems to be the result of impaired microcirculation of the oesophageal mucosa due to prolonged hypotension of variable aetiology. The diagnosis of black oesophagus requires exclusion of other causes such as ingestion of caustic materials and should be based on histological examination.

Adult↗
PubMed2004

Fatal influenza A infection with Staphylococcus aureus superinfection in a 49-year-old woman presenting as sudden death.

A fatal case of influenza A infection with Staphylococcus aureus superinfection in a previously healthy 49-year-old woman presenting as sudden, unexpected death is reported. Autopsy revealed severe necrotizing tracheobronchitis and hemorrhagic pneumonia. Microscopic examination of the trachea and bronchi showed mucosal necrosis and a dense lympho-monocytic infiltration of all layers. The lungs showed focal hemorrhagic pneumonia. No pathological changes were detectable in the myocardium. Influenza A virus was detected in bronchi and lung samples obtained during autopsy by the polymerase chain reaction (PCR) and bacterial superinfection with Staphylococcus aureus was shown by culturing from tracheal, bronchial and pulmonary swabs obtained during autopsy. PCR assays for the detection of Panton-Valentine leukocidin performed from all samples were negative. This case demonstrates the need for an interdisciplinary approach towards an organism-specific diagnosis of potentially infection-related deaths undergoing a medico-legal autopsy. With improved diagnostic possibilities such as PCR and DNA sequencing, forensic pathologists can, in close association with the field of microbiology, make a significant contribution to the detection of highly infectious agents which must be notified to the authorities. This will increase particularly the knowledge about the influence of these agents on sudden, unexpected deaths in outpatients.

Death, Sudden↗
PubMed2004

Pathologic features of suicidal complete decapitations.

Despite high suicide rates all over the world, complete decapitation as a consequence of violent suicide methods is exceptionally rare and there is always a potential for confusion with homicide as well as with body dismemberment or mutilation. We analyzed the phenomenology and morphology of 10 cases (six male, four female; individual age 18-60 years) of suicidal complete decapitation that were subjected to medico-legal autopsies at the Institute of Legal Medicine, University of Hamburg, Germany, between 1995 and 2002. All decapitations occurred while the person was alive as proven by signs of vitality. Blood alcohol levels were positive in five cases and ranged between 28 and 202 mg/dl. The applied methods of suicide were running over by a train in eight cases and hanging in two cases. In suicidal hanging resulting in complete decapitation the wound margins were clear-cut with an adjacent sharply demarcated circumferential band-like abrasion zone showing a homogenous width, the latter determined by the thickness of the rope. In decapitations due to railway interference a broad spectrum of pathologic alterations such as the co-existence of irregular, ragged and sharp-edged wound margins, vascular and nervous pathways forming bridges in the depth of the wound and bruising could be observed. In such cases skin abrasion zones were generally not circumferential and showed a heterogenous width. Concerning hanging-related complete decapitations, our findings are well in line with those of other authors, namely that heavy body weight of the suicidal, fall from a great height and in some cases inelastic and/or thin rope material used for the noose are the determining factors decisive for complete decapitation.

Adolescent↗
PubMed2004

Planned complex suicide. Report of two autopsy cases of suicidal shot injury and subsequent self-immolation.

Two cases of planned complex suicide are presented. In both cases, the suicidal persons shot themselves after making sure that in the sequel their bodies would be burnt. In the first case, a 65-year-old man had shot himself in the mouth and consequently fell into a fire he had lighted before. In the second case, a 43-year-old man set fire to his flat and shot himself directly afterwards. On the basis of the reported cases, a short literature review on planned complex suicides is given.

Adult↗
PubMed2004

Features characteristic of homicide in cases of complete decapitation.

Four cases of complete decapitation connected to homicidal acts are presented. In 3 cases, decapitation was inflicted postmortem after killing the victim. The motives for decapitation were considered defensive, aggressive, and a possible combination of the 2 in one case each. In one case, decapitation was a vital injury and accounted for death. In this case, an offensive motive for mutilation was suspected. The combination of death scene findings and autopsy results will in most cases distinguish between homicidal and other modes of death.

Adult↗
PubMed2004

Blunt cardiac trauma caused by fatal falls from height: an autopsy-based assessment of the injury pattern.

BACKGROUND: Falls from height are contributing widely to population morbidity and mortality, especially in urban settings. The presence of blunt cardiac injuries can increase morbidity among these patients, leading even to death. Some clinical studies and case reports have been published on the subject, but a systematic autopsy-based approach to the subject is missing in the literature of recent decades. METHODS: This study reviewed 61 cases of fatal fall from height that were subjected to a full autopsy at the Institute of Legal Medicine, Hamburg, Germany, from 1998 to 2002. The autopsy protocols and available clinical information were evaluated for assessment of the cardiac injury pattern. RESULTS: Cardiac injuries were found in 33 cases (54%), all of which involved falls from heights exceeding 6 m. In 16 cases, the cardiac injuries were the cause of death or contributed to the fatal outcome. In five of these cases, the individuals possibly could have recovered from their trauma if their heart injury had been sufficiently diagnosed and adequately treated in time. The most frequent finding was pericardial tearing (45%). Tears caused by stretching of the epicardium in the area wherein the inferior vena cava leads into the right atrium and epicardial hematoma were present in 11 cases (33%). Endocardial tears of the atria were found in six cases (18%), and did not occur during falls from heights lower than 11 m. Transmural tears to the right atrium were present in 10 cases (39%), and to the left atrium in 6 cases (18%). These tears occurred with increasing frequency in relation to greater heights. When the heights were lower than 15 m, these tears were smaller than 1 cm in diameter, but when the heights exceeded 15 m, extensive irregular tears were observed. Sternal fractures were seen in 76% of all cases involving heart injuries. In 16% of these cases, the fractures were multiple. Only 18% of the cases without cardiac injuries had sternal fractures, and none of these was multiple. Thus, the presence of severe sternal fractures can be used as an indicator of possible cardiac trauma. CONCLUSIONS: A thorough cardiologic diagnosis should always be performed for patients who survive a fall from height. These patients should be transported to a unit capable of performing cardiopulmonary bypass, and explorative thoracotomy should be considered.

Accidental Falls↗
PubMed2004

A pleiomorphic GH pituitary adenoma from a Carney complex patient displays universal allelic loss at the protein kinase A regulatory subunit 1A (PRKARIA) locus.

Carney complex (CNC) is a familial multiple endocrine neoplasia syndrome associated with GH-producing pituitary tumours and transmitted as an autosomal dominant trait. Mutations of the PRKAR1A gene are responsible for approximately half the known CNC cases but have never found in sporadic pituitary tumours. Pituitary tissue was obtained from an acromegalic CNC patient heterozygote for a common (PRKARIA)i-inactivating mutation. Both immunohistochemistry and electron microscopy showed a highly pleiomorphic pituitary adenoma. The cell culture population appeared morphologically heterogeneous and remained so after more than 30 passages. The mixture was comprised of cells strongly immunostained for GH, spindle-shaped myofibroblast-like cells, and cuboid cells with large axonal projections (negative for GH). The population appeared to have both epithelial and mesenchymal cells. Both at baseline and at passage 30, cytogenetic analysis indicated the presence of normal 46, XY diploid karyotype, whereas losses of the PRKARIA(i) locus were demonstrated in more than 98% of the cells by fluorescent in situ hybridisation, supporting this gene's involvement in pituitary tumorigenesis. Allelic loss may have occurred in a single precursor cell type that differentiated and clonally expanded into several phenotypes. Epithelial-to-mesenchymal transition may also occur in CNC-associated pleiomorphic pituitary adenomas.

Adenoma↗
PubMed2003

Beta-platelet-derived growth factor receptor mediates motility and growth of Ewing's sarcoma cells.

The Ewing's sarcoma family of tumors (ESFT) contain a translocation, t(11;22), which results in the novel oncogenic fusion protein EWS/FLI1. Platelet-derived growth factors (PDGF) and their receptors (PDGFR) are involved in the induction and proliferation of numerous solid tumors and are the potential candidates for novel targeted antitumor therapy. Since a relation was reported between PDGF-C and EWS/FLI1, we sought to characterize the PDGF signaling pathway in ESFT. Eight out of nine ESFT cell lines were found to express significant levels of beta-PDGFR. Interestingly, none of the tested cell lines expressed alpha-PDGFR, which is the receptor isotype required for PDGF-C binding. By immunohistochemical staining 47 of 52 (90.4%) archival tumor samples from patients with ESFT were positive for beta-PDGFR. ESFT cell lines were treated with PDGF-AA or PDGF-BB ligands to evaluate downstream signaling. Autophosphorylation of beta-PDGFR and tyrosine phosphorylation of PLC-gamma, PI3Kp85 and Shc were detected only in PDGF-BB-stimulated cells that express beta-PDGFR. Receptor function was further evaluated using chemotaxis assays that showed TC-32 cell migration towards PDGF-BB. A specific PDGFR kinase inhibitor AG1295 blocked beta-PDGFR activation, downstream signaling, growth in cell culture and chemotaxis of TC-32 cells. AG1295 also delayed tumor formation and prolonged survival in an ESFT animal model. We conclude that ESFT express beta-PDGFR and that this is a functional and potentially crucial signaling pathway. Therefore, beta-PDGFRs may provide a novel therapeutic target in ESFT that can be utilized to design better treatment modalities.

Animals↗
PubMed2003

Pathologic features of suicidal deaths caused by explosives.

Suicidal explosions that lack a terrorist background are only rarely encountered in the field of forensic pathology. The investigation of explosion-related fatalities can be a substantial challenge in medicolegal casework. Determining whether the manner of death is suicide, homicide, or accident in such cases can present an especially difficult task to the forensic pathologist. This study considers the pathologic features of suicidal deaths caused by explosives without a terrorist background. The modus operandi of the decedents reflected familiarity and proficiency, or at least a degree of specialized knowledge, with the construction and use of explosive devices. All explosions were set off in confined spaces. The injury patterns consisted of a combination of primary blast injuries (e.g. decapitation, traumatic amputation of limbs, gross lacerations of the body surface, blast injuries of gas-containing and hollow organs), secondary blast injuries (e.g. splinter-induced penetrating trauma), tertiary blast injuries (e.g. abrasions and contusions), and burn injuries (mostly of the flash type). The previously described symmetric distribution pattern of injuries in suicidal explosions was apparent only to a certain degree in the present series. Our observation of superficially sharp-edged wound margins with bridging in the depths of the lesion in blast-induced lacerations of the skin should deserve further attention in forthcoming cases of explosion-related fatalities because this finding is a diagnostic possibility that may support the theory of an explosion-related fatality under special circumstances, e.g. when the body has been dumped away from the place of death. Because a terrorist attack may be initially suspected in each case of suicide involving explosives, the importance of a joint inquiry based on expertise from police investigators, bomb experts, and forensic pathologists is evident.

Adult↗
PubMed2002

Expression of pulmonary lactoferrin in sudden-onset and slow-onset asthma with fatal outcome.

The objective of this forensic autopsy study was to determine the immunohistochemical expression pattern of lactoferrin (LF) in pulmonary tissue sections deriving from fatal slow-onset asthma (time interval between onset of asthma attack and death >2.5 h) and fatal sudden-onset asthma (cases in which death occurred within 1 h of the onset of an asphyxic asthma attack) relative to controls (sudden death due to diseases other than respiratory disorders). LF was applied to paraffin sections using a standard peroxidase-labelled streptavidin-biotin technique. LF immunoreactivity was graded semi-quantitatively in relation to different histoanatomic distribution sites of LF on a five category ordinal scale (maximum score of 15). We found a statistically significant difference between an enhanced expression of LF in both asthma groups relative to the controls (P<0.004 and P<0.001, respectively). When comparing both asthma groups, there was a statistically significant difference in LF immunoreactivity between the slow-onset and sudden-onset asthma group (P<0.001). Since LF immunoreactivity was far less intense in the sudden-onset asthma group (mean expression +/-SD: 7.3+/-1.3) than in the slow-onset asthma group (12.5+/-1), and an absent or weak LF expression pattern was observed in the control group (1.4+/-1.3), we assume that our results permit the following cautious estimations: (1) pulmonary LF expression is enhanced in asthma attacks with fatal outcome relative to controls and (2) a different expression pattern of LF can be observed in fatal sudden-onset asthma compared to slow-onset asthma in so far as the pulmonary expression of LF seems to be positively correlated with the preceding period of time between the asphyxic asthma attack and death. Further clinicopathologic studies including in-patient asthma fatalities with a well-known medical history are required to scrutinize if the pulmonary expression of LF is in fact positively associated with the time span of the asthma attack, thus possibly providing further therapeutic opportunities to intervene in severe asphyxic asthma.

Acute Disease↗
PubMed2002

Maternal death in pregnancy from HELLP syndrome. A report of three medico-legal autopsy cases with special reference to distinctive histopathological alterations.

Maternal death from HELLP syndrome, a complication of (pre-) eclampsia during pregnancy or postpartum, is rarely encountered in forensic pathology. We report three cases of HELLP syndrome with fatal outcome putting the main focus on the histopathological features of the disease. We found an almost identical histopathological pattern in the liver (periportal coagulation necrosis, hepatic haemorrhages sharply demarcated by an extended fibrin network from the surrounding unaffected liver parenchyma, focal leukostasis in liver sinusoids and swelling of Kupffer's cells, absence of inflammatory cellular infiltrates in liver plates, lack of fatty transformation of hepatocytes) and kidneys (bloodless glomeruli with swollen and vacuolated intracapillary cells, cigar-shaped capillary loops, enlarged glomerular tufts with herniation of capillary loops into the proximal convoluted tubules, swelling of mesangial cells) in all three cases. The histopathological alterations in the liver and kidneys can be considered characteristic for the disease and their presence may enable the forensic pathologist to establish the definite post-mortem diagnosis of HELLP syndrome in questionable cases.

Adult↗