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Biomedical subjects

W Grellner

Publications and source records attributed to W Grellner.

At least 19 recordsLinked to original sources
PubMed2004

Transforming growth factors (TGF-alpha and TGF-beta1) in the determination of vitality and wound age: immunohistochemical study on human skin wounds.

In continuation of former investigations on proinflammatory cytokines, in the present study the relevance of the transforming growth factors TGF-alpha and TGF-beta1 was evaluated for the diagnosis of vitality and wound age. Paraffin sections from human skin wounds due to sharp force influence, which had been collected in operations and autopsies, were investigated using immunohistochemistry. The wound age varied from a few minutes to a maximum of 6 weeks with focus on the early post-traumatic interval up to 5h. Samples from uninjured skin were available as controls. TGF-alpha (n=74) was weakly expressed in normal skin and showed a marked increase in epidermal reactivity after a wound age of approximately 10 min. The maximum was between 30 and 60 min. TGF-beta1 (n=51) revealed constitutional expression only in connective tissue. An increase of immunohistochemical reaction was partially detected even in classical stab wounds (wound age of several minutes). The immunohistochemically detectable signal concerned--presumably due to an infiltration with TGF-beta-rich thrombocytes--large parts of the traumatized skin and also the epidermal layers (cellular and interstitial marking). TGF-beta1 peaked after a post-traumatic interval of 30-60 min. Both factors, especially TGF-beta1, remained detectable in elevated levels also in older wounds with an age of days to weeks (network in granulation tissue). TGF-alpha and TGF-beta1 can efficiently contribute to the estimation of vitality and wound age based on the evaluation of cytokine patterns. In particular, this applies to TGF-beta1 because of its easier evaluation and rapid up-regulation. Similar to other cytokines, the parallel investigation of control skin from the same individual must be recommended to eliminate variation in the basal expression.

Biomarkers↗
PubMed2004

Fatal and non-fatal injuries caused by crossbows.

Today in modern times, traumatic injuries caused by crossbows are a rarity. The largest collection of cases so far is presented in this study, consisting of four fatalities (two homicides and two suicides) and two non-fatal injuries (grievous bodily harm and an accident). All the victims were male having an age between 31 and 54. The weapons, which were used, were mainly high-performance precision crossbows with telescopic sights and hunting bolts. The parts of the body involved were the facial/head area in three of the cases and the thorax in three of them. There were either deep or total penetration injuries to the cranium and thorax with the bolt remaining in the wound in four out of six cases. The persons with non-fatal crossbow injuries exhibited comparatively few symptoms, despite the sometimes extensive involvement of the interior of the cranium (cerebrocranial penetration, in one instance). The two cases of suicide favoured the body areas often found with gun-users. The aetiological classification of crossbow injuries may be difficult after the removal of the bolt. The external morphology is strongly dependent on the type of tip used. Multiple-bladed hunting broadheads produce radiating incised wounds, whereas conical field tips produce circular to slitlike defects. Correspondingly, the external injuries can be reminiscent of the effects of a violent attack by sharp force or of a gunshot wound. The possibility, supported by clinical data, that the victim might have the ability to act or even to survive for a period of time, even with penetration of the brain, should be taken into account when the cause of death is being investigated.

Accidents↗
PubMed2000

Quantitative analysis of proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha) in human skin wounds.

Proinflammatory cytokines play an important role in the mediation of inflammation and trauma. They could be useful for the determination of vitality and wound age. In the present study, 144 human skin wounds due to sharp force were investigated. The material was collected during operations (N=96) and postmortem examinations (N=48). The wound age varied from several seconds or minutes to 9 days. Control skin was available in each individual. The tissue specimens were homogenized and extracted in a solution of PBS and protease inhibitors. Interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) were measured by quantitative ELISA analysis. Statistical evaluation was performed by the t-test using the quotients of levels (wound sample/control skin). In surgical specimens the cytokine levels revealed a clear tendency to increase with wound age. IL-1beta in early skin wounds (</=30 min) and TNF-alpha after a wound age of 1-2 h demonstrated statistically significant changes in comparison with control skin (P<0.05). In autopsy samples with severe traumatization excessive elevation of cytokine levels was observed: IL-1beta, IL-6 and TNF-alpha showed significant increases (P<0.001-0.05) in stab and incised wounds with very short survival times of less than 5 min, but not in possibly supravital injuries. Elevated IL-6 levels persisted in older wounds (>24 h, P<0.05). The quantitative analysis of proinflammatory cytokines in wound extracts can contribute to the determination of vitality and wound age, in particular in the very early post-traumatic interval (classic stab wounds).

Aged↗
PubMed2000

Fatal outcome in a case of pontocerebellar hypoplasia type 2.

Pontocerebellar hypoplasia (PCH) is a very rare congenital (autosomal recessive) condition with fetal onset. Only a few cases have been published on the basis of both clinical data (symptoms/neuroradiological imaging) and autopsy results. This paper reports on such a case involving a 1.5-year-old male infant. The child suffered from severe psychomotor delay, extrapyramidal dyskinesia and epileptic seizures, but did not exhibit signs of spinal muscular atrophy as related to PCH type 1. Magnetic resonance imaging (MRI) at the age of 6 months demonstrated olivo-pontine and bilateral cerebellar hypoplasia. The boy was unexpectedly found dead. Autopsy disclosed a severe aspiration of gastric contents as the final cause of death. The neuropathological examination confirmed PCH type 2 (according to Barth [Brain Dev., 15 (1993) 411-422]) with marked microcephaly and olivopontocerebellar hypoplasia. Histologically, decreased density of olivo-pontine neurons, reduction of granular and Purkinje's cell layers of the cerebellum, slight astroglial proliferation and fragmented appearance of the dentate nuclei were observed. The immunohistochemical expression pattern was determined using antibodies against glial fibrillary acidic protein, synaptophysin and neurofilament protein. Summarizing, typical features of PCH type 2 were present and proved by clinical course, MRI and autopsy. Despite severe symptoms due to a natural disease this rare neurogenetic entity can become of forensic interest, when sudden unexpected death occurs.

Autopsy↗
PubMed1999

Death during percutaneous transluminal coronary angioplasty (PTCA) and the medicolegal aspects.

Coronary embolisation is a very rare complication of the clinically widespread method of percutaneous transluminal coronary angioplasty (PTCA). The well-documented case of a 64-year-old male patient is presented comparing angiographic and morphological findings. The occluded left anterior descending artery (LAD) was successfully dilated during PTCA. Simultaneously the circumflex artery showed acute occlusion. The patient fell into cardiac shock and died after attempted resuscitation and agonal installation of extracorporeal circulation. The autopsy revealed severe residual stenosis of the proximal LAD by parietal thrombosis and occlusion of the proximal circumflex artery by an unattached intraluminal thrombus (0.8 x 0.3 x 0.2 cm) which had been dislocated during PTCA. Autopsy thus confirmed the clinical presumption of coronary embolism and, in addition, disclosed a previously unknown perforation of the femoral artery which had occurred during agonal installation of extracorporeal circulation and contributed to death via severe retroperitoneal hemorrhage. The case is discussed under the aspects of clinical quality control by forensic pathological investigations.

Angiocardiography↗
PubMed1998

Immunohistochemical detection of fibronectin in postmortem incised wounds of porcine skin.

Fibronectin plays an important role in tissue repair and wound healing. Previous literature reports indicated that fibronectin could be a marker of vitality for wounds with a survival time of more than a few minutes. In order to verify these findings were performed immunohistochemical investigations on the expression of fibronectin in incised wounds of porcine skin inflicted into various anatomical regions in the early postmortem interval (0-5 min after circulatory arrest). Tissue specimens were collected 12-14 h postmortem and investigated for fibronectin on paraffin sections (alkaline phosphatase and monoclonal anti-alkaline phosphatase procedure). A markedly positive expression of fibronectin (not only next to the wound margin and clearly stronger than in normal undamaged skin) could be demonstrated in eleven out of 36 samples. A moderately positive fibronectin reaction was detectable in seven further specimens. Muscular contraction bands were observed in nine out of 36 specimens. The various reaction patterns of fibronectin cannot be finally explained, but are probably due to a passive transudation of skin tissue by blood components from injured vessels. As a result of these investigations the specificity and validity of fibronectin as a parameter of vitality has to be questioned. Fibronectin immunohistochemistry again reveals that the validity of parameters as vital criteria decreases when their manifestation time is short; postmortem/supravital induction seems to be possible resembling vital reactions in these cases.

Animals↗
PubMed1998

Medico-legal aspects of doping.

Abuse of anabolic steroids is an increasing problem not only among athletes but also body-builders and teenagers. A fast-developing black market has been established since the opening of the borders to eastern Europe. Medico-legal aspects of doping are addressed with particular reference to toxicology and pathology. Constituents of anabolic steroids bought on the black market were identified using gas chromatography/mass spectrometry; the products did not contain the expected ingredients in 35% of cases. Long-term effects and fatalities because of anabolic steroid abuse are reported here based on our own case material and a literature review. In our own cases, severe cardiovascular side-effects developed after long-term abuse of Dianabol (methandrostenolone) and Oral-Turinabol (chlordehydromethyltestosterone), i.e. myocardial infarction, stroke, organomegaly and/or severe atherosclerosis. The pathogenesis of cardiovascular complications (cardiotoxic effect, risk of atherosclerosis, thrombogenic risk) is discussed based on the available literature reports following fatal outcome after the abuse of anabolic steroids.

Journal Article↗
PubMed1997

Assessment of postmortem blood alcohol concentrations by ethanol levels measured in fluids from putrefactive blisters.

It was the aim of the present study to investigate whether the postmortem blood alcohol concentration (BAC) can be assessed by means of ethanol values measured in fluids from putrefactive blisters. Fluids from one or two putrefactive blisters were collected in 45 putrefied corpses (postmortem interval: 3-23 days, graduation of the degree of decomposition into four stages) and compared with femoral vein blood or femoral muscle. Ethanol and so-called putrefactive alcohols were determined in all samples by double GC-measurements. The results were converted to the medium water content of blood of 80%. The investigations revealed a significant correlation between the ethanol values of femoral blood/muscle and putrefactive blister fluid (PBF) (r = 0.725, P < 0.001). With the exception of one case, PBF values of 0.11% or more (n = 11) corresponded to minimum blood/muscle concentrations of 0.085%; PBF values of more than 0.15% (n = 8) corresponded to blood/muscle levels of at least 0.159%. Regression analysis revealed the formula BAC (in %) = 0.785 X ethanol (PBF) +0.011. Relevant concentrations of putrefactive alcohols such as 1- and 2-propanol and l-butanol only occurred in cases with far advanced decomposition. Ethanol levels determined in fluids from different putrefactive blisters of the same body also demonstrated a significant correlation (r = 0.791, P < 0.001). Ethanol concentrations determined in PBF must be judged with caution, but PBF values > 0.15% point to corresponding blood levels with a high degree of probability, at least where advanced putrefaction is excluded.

Alcohol Drinking↗
PubMed1997

Exhumations: synopsis of morphological and toxicological findings in relation to the postmortem interval. Survey on a 20-year period and review of the literature.

Before an exhumation the question of its possible success usually arises. This paper aims to act as an aid by providing comprehensive lists ("expectation catalogues") of morphological and toxicological findings with their corresponding postmortem intervals. All organ systems are included. The results are based on the retrospective evaluation of 46 exhumations performed at the Cologne Institute of Forensic Medicine in a 20-year period (1974-1994) and a review of the literature. In our own material (34 males, 12 females, age range: 2 days-91 years) the postmortem interval varied from 6 days to 20.5 years. Exhumations were performed by order of criminal courts (n = 28), social insurances (n = 13) and private persons (n = 5). Main indications were problems of causality in social and civil law (n = 14), suspected intoxications (n = 10), possible medical malpractice (n = 7), criminal aspects of traffic accidents (n = 7) and identifications (n = 5). The expectation catalogues include the following remarkable items (with postmortem interval) from our own material: coronary thrombosis (3.5 months), granulation tissue in myocardial infarction (3.5 months), myocardial fibrosis (2.5 years), coronary sclerosis (7.5 years), femoral vein thrombosis and pulmonary embolism (3.75 months), pneumonia (3 months), pulmonary emphysema and chronic bronchitis (2.5 years); detection of strangulation marks (2 months); preservation of bone marrow histology (3 months), gastrointestinal tract in continuity (7.5 years), macroscopic and histological cerebral structures (17 years); toxicological detection of phenobarbital (6 weeks), CO-Hb (9.5 weeks), chlorprothixene (5.5 years), diazepam (7.5 years), furosemide (7.5 years) and parathion (E 605) (17 years). The cause of death could be clarified with sufficient certainty in 36/46 cases (78%). Exhumation problems could be answered completely in 39 cases and partly in seven further cases. On the whole this review again underlines the importance and value of this special kind of body examination even after long postmortem periods.

Academies and Institutes↗
PubMed1997

Combination of fatal digoxin poisoning with endocardial fibroelastosis.

This is the first report in the forensic literature of a combination of fatal digoxin poisoning with endocardial fibroelastosis (EFE). Typical morphological features of EFE as the cause of clinically diagnosed cardiomyopathy were present in the autopsy of a 3-year-old girl, including cardiac hypertrophy and marked thickening of the left-sided endocardium, consisting of numerous elastic and collagenic fibres. After exclusion of cardiac and cerebral causes of death, accidental digoxin intoxication was proved. Postmortem toxicological analyses by fluorescence polarization immunoassay (FPIA) disclosed digoxin levels of 71 micrograms/kg (femoral vein blood), 77 micrograms/kg (cardiac blood), 255 and 221 micrograms/kg (cardiac muscle of the right and left chamber), 163 micrograms/kg (psoas muscle), 91 micrograms/kg (lung), 222 micrograms/kg (liver) and 520 micrograms/kg (kidney). The results are compared with the antemortem digoxin concentration of 39 ng/ml serum. The case is discussed from its unusual morphological and toxicological aspects, with special consideration of possible medical malpractice.

Cardiotonic Agents↗
PubMed1997

The quantitative alteration of the DNA content in strangulation marks is an artefact.

UNLABELLED: It is frequently difficult to prove the vitality in cases of fatal hanging. Using impulse cytophotometry, Müller et al. (Krim. Forens. Wiss. 44, 1981) reported on possibly vital alterations of the DNA content in five strangulation marks (hypodiploidy). The objective of the present study was to perform a re-evaluation by means of current methods of quantitative DNA analysis. The investigation included 24 cases of hanging (typical, n = 11; atypical, n = 13). DNA was extracted by use of phenol/chloroform and quantitated photometrically in relation to the tissue weight. In addition, skin specimens were examined histologically and their water content was determined. The mean DNA content of strangulation marks was 3.2 micrograms DNA/mg tissue, that one of uninjured skin (control) 1.4 microgram DNA/mg tissue. The ratio of DNA content between strangulation grooves and control skin varied from 1.2 to 5.2 (average: 2.4) implicating apparently elevated DNA levels in strangulation marks. Histology revealed typical changes with absence of leukocyte infiltration suggesting mechanical compression of DNA containing layers. The additional determination of the water content emerged-in dependence on the macroscopic appearance, dried or non-dried-reduced values for strangulation marks (average: 42% vs. 66%). Statistical analysis demonstrated a significant correlation between elevated DNA content and reduced water content of strangulation marks. CONCLUSION: the markedly elevated DNA content of strangulation marks is interpreted as an artefact due to drying of the skin with a reduction of the water content (and weight) in the course of mechanical cutaneous alterations (compression). Therefore, quantitative changes in the local DNA content of the groove have no importance as a sign of vitality in fatal strangulations.

Artifacts↗
PubMed1996

Immunohistochemical characterization of alveolar macrophages and pulmonary giant cells in fatal asphyxia.

UNLABELLED: It is in dispute whether the occurrence of numerous alveolar macrophages and in particular pulmonary giant cells in cases of fatal asphyxia is associated with agonal activation and proliferation. The nature of these alveolar cells was investigated in selected fatalities with protracted final oxygen lack using immunohistochemistry (APAAP method) and a semi-quantitative graduation. The study included opiate-involved deaths (n = 22), fatal strangulations (n = 10) and a control group of sudden cardiovascular deaths (n = 10). Positive immunohistochemical reactions were observed with the monoclonal antibodies PG-M1 (general marker of macrophages, detection of nearly 100% of pulmonary macrophages and giant cells in all subgroups) and 25 F 9 (late stage inflammation marker, detection of pulmonary macrophages/giant cells in 70%/50% of opiate-involved fatalities, 70%/20% of strangulations and 40%/30% of control cases). The antibodies LN-4 (macrophages), 27 E 10 (early stage inflammation marker), AMH 152 (activated macrophages) and MIB 1 (proliferation marker) did not react with these cell populations. CONCLUSIONS: pulmonary giant cells and numerous alveolar macrophages are not restricted to asphyxia. Their appearance is not of pathognomonic value for this diagnosis. Both cell types seem to be of heterogeneous nature (different functional state) as only one marker was expressed by all cells. The results do not suggest prefinal immigration, mobilization or proliferation of alveolar cells, but rather point to a longer pre-existence of macrophages and giant cells in pulmonary tissue (25 F 9 as late stage inflammation marker positive).

Antibodies, Monoclonal↗
PubMed1996

Multiple cardiac rhabdomyoma with exclusively histological manifestation.

Rhabdomyomas of the heart are rare lesions and usually exhibit macroscopic tumour nodules at autopsy. The uncommon death of an apparently healthy 2 1/2-month-old female infant is described. Post-mortem examination revealed normal gross cardiac morphology and exclusively histological manifestation of multifocal rhabdomyoma. The microscopic and immunohistochemical features are demonstrated. Tuberous sclerosis, frequently associated with this type of hamartoma was not present. The case confirms again the importance of additional histological investigations in unexpected fatalities in infancy: beside the clarification of death, autopsy may obtain a prophylactic function in the detection of possibly genetically determined diseases such as cardiac rhabdomyoma.

Female↗
PubMed1996

Interleukin-1 alpha (IL-1 alpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) as potential inducers of supravital chemotaxis.

The phenomenon of artificially induced local leucocyte reactions during the supravital period could be of practical importance, but has not yet been comprehensively investigated. For a more detailed evaluation, experiments with the chemotactic agents interleukin-1 alpha (IL-1 alpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) were performed by subcutaneous injection into various anatomical regions (back, abdomen, limbs) of NMRI-mice (National Medical Research Institute) and pigs 0-5 min after circulatory arrest. Phosphate buffered saline (PBS) without effective components was administered to equivalent areas of the animals as a control. Tissue specimens were collected at 6 h postmortem (mice) and 12-14 h postmortem (pigs), cut into serial sections, stained with H & E and examined under the microscope. A leucocyte reaction did not develop in pigs (n = 10, 30 tissue samples) following injection of FMLP, however, dermal, subcutaneous and perivascular infiltration of leucocytes (in particular mononuclear cells and a few granulocytes) was found in 3 out of 30 tissue specimens in murine experiments. In addition intravascular cell accumulations were detected in 2 out of 30 samples. The injection of IL-1 alpha to mice gave similar results, i.e., aggregations of leucocytes and intravascular cell accumulations in 4 out of 30 and 3 out of 30 tissue samples, respectively. In negative controls no leucocyte reaction was detectable. This shows that potent chemotactic factors such as IL-1 alpha and FMLP administered in the early supravital period can induce moderate local leucocyte reactions in animal models in at least some cases. A clear morphological differentiation between vital and supravital chemotaxis does not seem to be possible. The supravitally stimulated accumulations of leucocytes are interpreted as an aggregation of resident macrophages in combination with a slight migration of blood leucocytes. Presumably, these alterations are restricted to the very early supravital period as long as sufficient energy reserves are available. It must be stated that the observed changes are reactions, not spontaneous actions, so that the general validity of the phenomenon of leucocyte infiltration as a vital parameter is not affected.

Animals↗
PubMed1996

Pulmonary histopathology and survival period in morphine-involved deaths.

For an evaluation of the survival period in morphine-involved deaths, changes of pulmonary histopathology were investigated in a total of 90 morphine-associated fatalities. Although pulmonary histopathology proved to be heterogeneous, several distinctive histological patterns emerged. While the subgroup with short courses of intoxication ( < 1 h, n = 15) was mostly characterized by slight/moderate alveolar edema (12/15), severe hemorrhages (12/15) and marked acute emphysema (9/15), the phenomena of massive edema (8/15), missing/slight hemorrhages (8/15) and absent/slight emphysema (11/15) dominated in the group with intermediate survival times (1-24 h, n = 15). Intravascular leukocyte accumulations (shock equivalent) occurred in the first group only once, but in the group with the longer survival time in 10 of 15 cases. Delayed deaths ( > 24 h, n = 4) were mainly characterized by purulent bronchitis/pneumonia. Those fatalities (n = 56) that could not be classified by anamnestic data were assessed by histological criteria. In comparison with the evaluation of the survival period by toxicological analyses, concordance was found in 46 cases. Pulmonary histopathology is not a tool for an exact graduation of survival time, but the combination of several key parameters can provide criteria for a differentiation between short ( < 1 h) and longer courses of intoxication.

Adult↗
PubMed1995

Multiple skeletal muscle metastases from malignant pleural mesothelioma.

A 54-year-old male patient (occupational asbestos exposure over 27 years) died 2 years and 4 months after the diagnosis of malignant pleural mesothelioma of the right side, despite twice undergoing pleurectomy and radiotherapy. The autopsy revealed a locally advanced pleural mesothelioma of both sides involving the pericardium, heart, right diaphragm, liver and peritoneum. Disseminated metastases in numerous lymph nodes and a hematogenous metastatic spread into both lungs, the thyroid gland, peritoneum and skeletal musculature were found. The left temporal muscle and proximal limb skeletal muscles of the right upper arm and both thighs exhibited multiple metastases measuring up to 7 cm in diameter. Microscopically, a biphasic type of mesothelioma was detected. To our knowledge this is the first extensive case report on muscle metastases in malignant mesothelioma. Reviewing the literature, it is thought that in the presented case the long survival time of the patient and his protracted preterminal immobility could have contributed to the unusual formation of multiple skeletal muscle metastases.

Asbestos↗
PubMed1995

[Fatal outcome of a congenital aneurysm of the right sinus valsalvae ruptured into the right atrium].

In a 24-year-old female patient with sudden collapse an acute tricuspid insufficiency was presumed by echocardiography after the exclusion of pulmonary embolism. Aortography, however, revealed an aneurysm of the right sinus of Valsalva which had ruptured into the right atrium. Despite emergency surgery the patient died in protracted cardiac shock. Biopsy and autopsy showed pathognomonic findings of a congenital aneurysm (medial degeneration, reduction of elastic lamellae). Aneurysms of the sinuses of Valsalva are mainly caused by a rare connatal defect of the aortic wall; the right aortic sinus is involved most frequently, the sudden rupture uncovers the lesion. The characteristics of the reported case are compared with the literature under special consideration of etiology and pathologic anatomy of this unusual entity.

Aortic Aneurysm↗