Biomedical subjects

Michael Tsokos

Publications and source records attributed to Michael Tsokos.

At least 19 recordsLinked to original sources

PubMed2006

Postmortem diagnosis of sepsis.

Human sepsis is a spectrum of pathophysiological changes in the host system resulting from a generalized activation and systemic expression of the host's inflammatory pathways in response to infection. Since autopsy findings and routine histology in cases of suspected fatal sepsis are most often unspecific and unconvincing, a number of studies has recently dealt with different methods and markers to better define criteria for the postmortem diagnosis of sepsis. Research carried out on specimens obtained postmortem from sepsis-associated fatalities is an important tool to improve our understanding of inflammatory organ changes and the associated underlying pathophysiological mechanisms. One pitfall the investigator has to be aware of is how to select appropriate case material that constitutes the basis for the setting-up of reference values that derive from such studies. Since no scientific studies have investigated the value of cardiac blood samples in the present context, autopsy blood samples for the determination of biochemical sepsis markers have to derive from the femoral vein. In both sepsis cases as well as controls, the time of death has to be well defined.

Biomarkers↗

PubMed2006

Haemolytic staining of the intima of the aortic root-- a useful pathological marker of freshwater drowning?

UNLABELLED: The significance of haemolytic staining of the aorta is unclear. While it has been associated with freshwater drowning, data are lacking. To study this phenomenon further a prospective study looking at the colour of the intima of the pulmonary trunk and aortic root was undertaken in 47 randomly selected coronial control cases and in 13 consecutive fresh drowning deaths. There were 16 putrefied control cases each of which showed haemolytic staining of both great vessels. Of the other 44 non-putrefied cases (31 controls, 9 saltwater drownings, and 4 freshwater drownings), only one (a freshwater drowning) showed marked staining of the aortic root with no staining of the intima of the pulmonary trunk. CONCLUSION: This study has demonstrated that haemolytic staining of the aorta at autopsy, in the absence of significant staining of the pulmonary trunk and putrefaction, may be a pathological feature that is supportive of freshwater drowning. It is not, however, present in all cases. Given the relatively small numbers in this study further work is required to clarify this issue.

Adolescent↗

PubMed2006

Drowning, haemodilution, haemolysis and staining of the intima of the aortic root-- preliminary observations.

In order to demonstrate that hyponatraemia due to haemodilution occurs within the left ventricle following freshwater drowning, and to determine whether lysed blood resulting from left ventricular haemodilution may cause staining of the aortic intima, the following studies were undertaken. Measurements of left ventricular sodium levels were performed in 74 consecutive coronial cases where death was attributed to drowning, consisting of 44 and 30 deceased who were believed to be victims of freshwater and saltwater drowning, respectively. Left ventricular sodium levels differed significantly between the two groups (p<0.001), with a range of 93-147 mmol/L in freshwater drowning (mean=117+/-14.2 mmol/L) and 123-183 in saltwater drowning (mean=153+/-14.4 mmol/L). In addition, the mean sodium level of 117 mmol/L in freshwater drowning was significantly lower than the standard range of 137-145 mmol/L. In a second study, portions of aorta and pulmonary trunk from a euthanised pig were soaked in lysed blood resulting in marked haemolytic staining of the intima of both vessels after 20 min. Water and a mixture of blood and water were then injected into the left ventricles in two further pig carcasses, respectively, resulting in haemolytic staining of the intima of the aortic roots, with no staining of the pulmonary trunks. These studies have confirmed that significant hyponatraemia secondary to haemodilution may occur within the left ventricle in freshwater drowning, and that haemolysed blood is capable of causing staining of the aortic root in an animal model. These results provide further data to support haemolytic staining of the aortic root intima as a possible manifestation of freshwater drowning.

Adolescent↗

PubMed2006

Over-expression of p53/BAK in aseptic loosening after total hip replacement.

Particle-induced osteolysis is a major cause of aseptic loosening after total joint replacement. The possible induction of apoptosis has not been addressed in great detail. Thus far, it has been shown that ceramic and polyethylene particles can induce apoptosis of macrophages in vitro. The purpose of this study was to test the hypothesis that wears debris generated from total hip arthroplasty could induce cellular damage and apoptosis in vivo. We therefore determined by immunohistochemical methods if increased expression of p53, an important transcription factor, and BAK and Bcl-2, two important regulators of apoptosis, can be found in interface membranes and capsules of hips with aseptically loose implants. Strongly positive immunohistochemical staining for p53 and BAK was found in peri-implant tissues from patients with aseptic hip implant loosening. Differentiation of various cell types showed that macrophages stained positive for p53 in all capsule and interface specimens. p53 was frequently detected in giant cells. Positive staining of BAK in macrophages and giant cells was seen in all specimens. Some positive reactions were observed in fibroblasts, only two of 19 cases stained for p53 and three cases for BAK within synovial cells. Positive macrophages and giant cells were localized around polyethylene particles. While T-lymphocytes showed a regular BAK-staining, the other leukocytes were negative. Statistical analyses showed significant positive correlations (p < 0.001) between the presence of polyethylene and metal debris and the expression of BAK and p53. Polyethylene particles were surrounded by more positive macrophages and giant cells than were metal particles, indicating that polyethylene debris may be a stronger inductor of cell cycle arrest and apoptosis than metal debris. In this study apoptosis of macrophages, giant cells and T-lymphocytes in capsules and interface membranes of patients with aseptic hip implant loosening has been demonstrated in vivo. It is possible that the apoptotic cascade could evolve as a novel therapeutic target to prevent particle-induced osteolysis.

Adult↗

PubMed2006

Prognostic value of mucins in the classification of ampullary carcinomas.

The ampulla of Vater is of high clinical relevance with regard to influx of chyme, ascending inflammation, intubation during diagnostic and therapeutic endoscopic investigation, therapeutic papillotomy, and especially to malignant transformation. Little is known about the distribution of mucins in the ampulla. In this study, we have investigated the mucin distribution in the normal ampulla of Vater and compared it to duodenal mucosa and Brunner glands. Expression of mucins in the ampulla of Vater and duodenum was monitored by reverse transcription-polymerase chain reaction and localization of the products by immunohistochemistry. The samples investigated originated from 30 autopsy cases. Mucins MUC1, MUC3, MUC4, MUC5AC, MUC5B, MUC6, MUC7, and MUC8 were expressed in the ampulla of Vater. Immunohistochemistry revealed production of MUC4, MUC5AC, MUC5B, and MUC6. The mucin composition varied in comparison with the duodenum referring to MUC2, MUC7, and MUC8. Detected mucins contribute to innate immunity, epithelial restitution, and protection against the aggressive secretions of the liver, gall bladder, and pancreas. By cross-linking, they influence the rheological properties of the secretions in the ampulla and facilitate unidirectional flow into the duodenum. Knowledge of their pattern of expression has prognostic value with regard to the detection of malignancy. The observed differences in the mucin distribution between the duodenum and the ampulla of Vater support the use of MUC2, MUC7, and MUC8 as useful tool in the classification of ampullary carcinomas.

Adult↗

PubMed2006

Ultrasound in the diagnosis of craniosynostosis.

Diagnosis of craniosynostosis is based on clinical aspects but may be difficult in some cases where characteristic features are missing and radiographic imaging is necessary. In this context near-field high-frequency ultrasound has been used to evaluate the sonographic characteristics of synostotic sutures and its potential confirming the correct diagnosis. Sutures of 26 infants, aged 2-7 months, were investigated by ultrasound (Siemens Elegra, 7.5 MHz linear scanner). Sonographic features of synostotic sutures were correlated to CT imaging and compared to the sonographic and histopathological findings of normal cranial sutures. Hyperechogenic bridging of sutures with or without ridging were the characteristic aspects of synostotic sutures. All 26 patients could be reliable diagnosed showing partial (n = 21) or total fusion (n = 5) of one or more sutures consisting with craniosynostosis. Length of synostosis was identified exactly by sonography and imaging found to enable a classification of ultrastructural details of bony and soft tissue next to the synostotic suture. Ultrasound is a less expensive, nonradiating and easy-to-handle tool ensuring the diagnosis of craniosynostosis. Sonography offers the potential to be a standard investigation for infants with head deformities suspecting a suture pathology and has been therefore integrated in our craniofacial outpatient clinic as a daily routine method.

Cranial Sutures↗

PubMed2006

Putrefaction and wound dehiscence: a potentially confusing postmortem phenomenon.

The decomposed body of a 49-year-old man was found at his home address. At autopsy, 3 incised wounds of the lower abdomen and groins were identified, raising the possibility of some form of inflicted injury. Further dissection revealed that the wounds were healing surgical incisions that had been forced open by putrefactive tissue breakdown, swelling, and gas formation. Death was due to ischemic heart disease. Putrefaction is a common problem encountered in forensic practice that may result in considerable distortion and modification of tissues. Unusual skin lesions caused by the disruption and dehiscence of healing surgical wounds may be created by decomposition. This possibility should be considered when symmetrical, cleanly incised wounds are identified.

Abdomen↗

PubMed2006

Histological and immunohistochemical study of Wischnewsky spots in fatal hypothermia.

Wischnewsky spots in the gastric mucosa are considered an important finding for the diagnosis of hypothermia-related deaths. In the present prospective histological and immunohistochemical investigation, 14 cases of fatal hypothermia presenting Wischnewsky spots at autopsy were studied. Macromorphologically, the lesions, varying in diameter from 0.1 to 0.4 cm, had a blackish-brownish color and appeared partly lofty, especially on the apex of gastric folds. Histologically, no erosions or ulcers were observed in the gastric mucosa. In some cases, hemorrhages in conjunction with infarctions of the mucosa were observed in the mucosal glands. Those regions, however, did not represent the lesions visible as Wischnewsky spots at the macroscopical level. Immunohistochemical stains were done with a specific antibody against hemoglobin (Dako, Glostrup, Denmark). Wischnewsky spots expressed immunopositivity with antihemoglobin. Concerning the pathogenesis and underlying pathophysiologic mechanisms contributing to the development of Wischnewsky spots, we hypothesize that cooling of the body in the setting of cold ambient temperatures primarily leads to circumscribed hemorrhages of the gastric glands in vivo or in the agonal period, respectively. Subsequently, due to autolysis, erythrocytes are destroyed and hemoglobin is released. Following exposure to gastric acid, hemoglobin is hematinized, leading to the typical blackish-brownish appearance of Wischnewsky spots seen at gross examination. Wischnewsky spots are not equivalent to erosions in terms of histopathological diagnosis but rather represent epiphenomena generated in vivo or in the agonal period of fatal hypothermia.

Adult↗

PubMed2006

Avulsion of the distal tibial shaft in aircraft crashes: a pathological feature of extreme decelerative injury.

A pilot and his passenger were killed on impact with the ground when their light aircraft crashed. Both deaths were caused by extensive injuries involving severe craniocerebral, skeletal, soft tissue, and organ trauma. In both victims, the legs were shortened, with stripping of muscle and soft tissues from the shafts of the lower limb long bones. In addition, fragments of distal tibial shaft had been forced through the soles of the victims' shoes. This sign indicated a fall from height and showed that the direction of the decelerative forces had been along the axis of the legs and that the force of impact was severe enough to cause fracturing of the lower limb bones, with subsequent extrusion of bone fragments downwards through the shoes. When present, this observation represents another feature at autopsy that can add to the understanding of the circumstances of a fatal air crash and the position of the victims immediately prior to impact.

Accidents↗

PubMed2005

Black thyroid: report of an autopsy case.

A distinctive but very rare side effect of exposure to minocycline is black pigmentation of the thyroid gland. Until 2002, not more than 30 cases of black thyroid had been reported in the English literature. We report on a 24-year-old woman with known antemortem ingestion of minocycline. The woman suffered from a depressive disorder with repeated suicide attempts and committed suicide by a gunshot to the head. At autopsy, the thyroid gland showed coal-black coloration. Upon histology, clumps of black-brown pigment were seen in the colloid, and a granular precipitate of this pigment was noted in the apical portions of the follicular epithelial cells. The diagnosis of minocycline-associated black thyroid was established. Forensic pathological significance of black thyroid may arise from the fact that hypothyroidism has been occasionally associated with minocycline-related black thyroid and that hypothyroidism may contribute to the development of depressive disorders (and thus, in given cases, may be responsible for suicide attempts). Under this assumption, the presence of black thyroid would represent more than just a morphological curiosity in specific cases.

Adult↗

PubMed2005

Trefoil factor family (TFF) peptides of normal human Vater's ampulla.

Vater's ampulla is of great clinical relevance with regard to the influx of chyme, ascending inflammation, intubation during diagnostic and therapeutic endoscopic maneuvers, therapeutic papillotomy and, especially, the formation of malignancies. Little is known about the distribution of trefoil factor family (TFF) peptides in the ampulla. We have therefore examined TFF peptide distribution in the normal ampulla of Vater and compared it with that in duodenal mucosa and Brunner's glands. Expression and synthesis of TFF peptides in Vater's ampulla and duodenum was investigated by reverse transcription-polymerase chain reaction, Western blot and immunohistochemistry. The samples studied originated from 30 autopsy cases with short postmortem intervals. TFF3 was expressed in the ampulla of Vater. mRNA expression of TFF1 was detected in only approximately 25% of the investigated samples. Western blot revealed the production of TFF3 and immunohistochemistry showed that TFF3 was the product of goblet cells. TFF peptide composition of Vater's ampulla varied in comparison with that in the duodenum regarding TFF2 expression. The ampulla of Vater thus has a unique profile of TFF peptide production, supporting the hypothesis that the ampulla is an autonomous organ. The observed differences in the TFF peptide distribution between the duodenum and Vater's ampulla favour the investigation of TFF peptides as prognostic markers in the classification of ampullary carcinomas.

Adult↗

PubMed2005

Sudden unexpected death due to undiagnosed glioblastoma: report of three cases and review of the literature.

Although glioblastomas are among the most common primary cerebral neoplasms, sudden death due to these tumors is an uncommon event. Due to the usual rapid increase in intracranial pressure, patients develop symptoms rather early, leading to medical attention in time. A search for cases of sudden unexpected death due to undiagnosed glioblastoma from a total of 14,482 cases from the archives of the Institute of Legal Medicine in Hamburg in the period of 1991-2003 revealed only one such case. Out of a total of 5,432 cases from the Institute of Neuropathology, Hamburg, during the same period, two further cases were found. A comprehensive literature review on cases of sudden death due to primary cerebral neoplasms published so far revealed a total of 83 cases with only ten cases of glioblastoma (12%), whereas 55 of these cases were due to histological benign tumors (66%).

Adult↗

PubMed2005

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↗

PubMed2005

Skin tension and cleavage lines (Langer's lines) causing distortion of ante- and postmortem wound morphology.

The assessment of individual wounds at autopsy may be complicated by the superimposition of a number of injuries or damage to tissues that occurred after death, either of which has the potential to distort the morphology of the initial injury. Additional factors that may change the shape of wounds are (1) the relationship of the wound to the so-called skin cleavage lines (Langer's lines) and (2) tension placed on the skin. Three autopsy cases are reported to demonstrate once more how wound morphology may be altered by such factors. In case 1, rectangular stab wounds to the base of the neck in a 53-year-old man, which suggested that a square or rectangular tool may have caused the injuries, were altered to more typical knife stab wounds once skin tension had been released at autopsy. The uppermost wounds, however, continued to gape due to the effects of skin cleavage lines. In case 2, slit-like wounds resembling stab wounds in the neck of a 54-year-old woman found in a river were shown to be circular once skin tension had been released. In case 3, the effects of either cleavage lines or skin tension could be demonstrated on excised wounds from a 43-year-old man whose body had also been found in a river; tensile forces easily changed circular into slit-like wounds. Tension and/or skin cleavage lines may transform round skin defects into slit-like wounds resembling knife stab wounds, round out genuine stab wounds and artefactually lengthen stab wounds. These factors must be taken into consideration carefully when wounds are assessed at the death scene prior to autopsy.

Adult↗

PubMed2005

Fatal hypernatremia after using salt as an emetic--report of three autopsy cases.

Although a plethora of reports on life-threatening complications of salt emesis has been published since the early 1960s, salt is still used to induce emesis in cases of intoxication in the clinical as well as in the domestic setting. We report three cases of fatal hypernatremia after salt was used as an emetic. All fatalities were subjected to medico-legal autopsy at the Institute of Legal Medicine in Hamburg, Germany. In all cases, symptoms of cerebral damage such as seizures, fever and somnolence developed within hours after salt ingestion. All individuals were admitted to hospital before their deaths. Here, severe hypernatremia (up to 245 mmol/l) was detected, and all patients died under the clinical picture of cerebral edema despite intensive medical treatment. At autopsy, unspecific signs of a central regulatory failure were present. Histology revealed crenated red blood cells and few venous microthrombi in internal organs. Neuropathological investigations yielded no specific results but confirmed fatal cerebral edema and excluded other cerebral causes of death. Viewing the results of clinical and post-mortem investigations together, death could clearly be attributed to excessive salt intake in all cases.

Adult↗

PubMed2005

Sudden, unexpected death due to splenic artery aneurysm rupture.

Splenic artery aneurysms are an uncommon form of vascular disease that have a significant potential for rupture, resulting in life-threatening intraperitoneal hemorrhage. We describe the case of a 33-year-old man who died suddenly and unexpectedly due to the rupture of a splenic artery aneurysm. At medicolegal autopsy, 3000 mL of fluid blood were recovered from the peritoneal cavity. The source of bleeding was a sack-like aneurysm of the splenic artery, measuring 2 cm in diameter. Histologic examination of the splenic artery aneurysm revealed fibromuscular dysplasia. No atherosclerotic lesions or any inflammatory changes were apparent within the wall of the splenic artery. Portal hypertension and pancreatitis, previously described as important factors promoting splenic artery aneurysm formation, were excluded by autopsy and histology. From the forensic pathologist's viewpoint, this rare case underlines the importance of splenic artery aneurysm rupture as a relevant differential diagnosis of intraperitoneal hemorrhage and sudden death, respectively, since such cases may be misinterpreted as a result of blunt-force trauma.

Adult↗

PubMed2005

Vehicle-assisted suicide resulting in complete decapitation.

A rare case of vehicle-assisted suicide in a 43-year-old man is presented. The man had tied a rope between a fence and his neck and, while seated on the driver's seat, accelerated the vehicle, which resulted in complete decapitation. Earlier that day, the man had tried to bleed himself to death by bottling his own blood in his flat, thus defining the case as secondary complex suicide.

Adult↗

PubMed2004

Serial monitoring of interleukin-1beta, soluble interleukin-2 receptor and lipopolysaccharide binding protein levels after death A comparative evaluation of potential postmortem markers of sepsis.

We prospectively monitored the postmortem course of interleukin-1beta (IL-1beta), soluble interleukin-2 receptor (sIL-2R) and lipopolysaccharide binding protein (LBP) in septic and non-septic fatalities to evaluate their potential as biochemical postmortem markers of sepsis. Serum concentrations were determined by chemiluminescent immunometric assays. In both the sepsis group and the control group a postmortem increase of IL-1beta levels with the progression of time after death was observed, in both groups mainly starting from the reference concentration of healthy individuals (5 pg/ml) and with no significant differences at later time points postmortem. SIL-2R (reference limit 1,000 U/ml) was highly elevated in all individuals included in the sepsis group at all time points postmortem with statistically significant differences between the sepsis and control groups (p<0.01). An excessive postmortem decrease of sIL-2R serum levels associated with progression of time after death was observed in all cases included in the sepsis group in contrast to just 1 out of 16 control cases. LBP (reference limit <10 g/ml) was elevated in all sepsis cases whereas in the control group LBP levels were below 10 microg/ml in 88%. The postmortem time course of LBP serum concentrations showed a continuous increase in both the sepsis and control groups. We conclude that sIL-2R and LBP seem to represent appropriate diagnostic tools for the postmortem diagnosis of sepsis in forensic autopsy practice. sIL-2R serum levels above 1,000 U/ml and LBP serum levels above 10 microg/ml in peripheral venous blood obtained in the early postmortem interval can be regarded as diagnostic hints for an underlying septic condition in a deceased person.

Acute-Phase Proteins↗