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I Pedal

Publications and source records attributed to I Pedal.

At least 19 recordsLinked to original sources

Medicolegal assessment of blood transfusion errors--an interdisciplinary challenge.

Given a current total incidence of erroneously administered blood transfusions of 1:12,000-1:36,000 (AB0 incompatible 1:38,000), the percentage of lethal outcomes ranges between 2 and 5%; i.e. the sole fact of an erroneous transfusion does not mandatorily result in a causal connection with lethal outcome, which can give rise to problems in the medicolegal assessment. We report on the conception and results of a novel interdisciplinary approach to assess the lethal significance of blood transfusion errors. Besides autopsy, histological investigation and immunohistochemical detection of AB0 incompatible foreign red blood cells in autopsy specimens, transfusion medicine investigations offer the opportunity to assess several immunohaematologic features. We assessed the immunohaematologic gel card ("microcolumn") technique for suitability in the forensic assessment of an AB0 incompatible transfusion incident in a septic patient, who had had no history of previous blood transfusions, with lethal outcome. After such an erroneous transfusion had been simulated in vitro, pre-transfusion and cadaver patient blood samples (p.m. interval: 3 days) were analysed. Amongst other things, IgG-loaded erythrocytes were detected in pre- and post-transfusion samples; the presence of irregular antibodies directed against blood group antigens and anti-A or anti-B isoagglutinins, respectively, especially in the pre-transfusion sample was ruled out. Besides the demonstration of AB0 incompatible red blood cells in the cadaver blood sample, blood group incompatibilities other than AB0 were excluded. With regard to the cause of death, in synopsis with autopsy findings and clinical symptoms, the results did not allow for a final discrimination between the impact of the pre-existing septic inflammatory response syndrome and sepsis, respectively, and potential lethal effects of a (haemolytic) transfusion reaction. Besides pre- and post-transfusion compatibility testing in clinical transfusion medicine as required by German National Guidelines, the reported immunohaematologic investigations offer an important supportive tool for the forensic assessment of lethal erroneous transfusions and investigation of blood samples of survivors of transfusion incidents as well. Besides established morphological techniques, they allow for a certain evaluation of the pathophysiological impact of transfusion incidents as well as a diversified assessment of immunohaematologic features beyond the AB0 system.

ABO Blood-Group System↗

Increase in nerve fibers and loss of mast cells in polycystic and postmenopausal ovaries.

OBJECTIVE: To quantify nerve fibers and mast cells in human ovaries at different functional stages. DESIGN: Retrospective study. SETTING: Research laboratory of the university. SPECIMEN(S): 8 human ovaries in the follicular (cyclic) phase, 7 polycystic ovaries, and postmenopausal ovaries with (n=5) or without (n=7) hyperthecosis. MAIN OUTCOME MEASURE(S): Single- and double immunohistology for the S100 antigen in glial cells of autonomic nerve fibers, for chymase and tryptase in mast cells, and for the common leukocyte antigen on leukocytes. Histometric evaluation was also performed. INTERVENTION(S): None. RESULT(S): Polycystic ovaries contained significantly more S100-positive nerve fibers in the corticomedullary region than did cyclic ovaries (mean +/- SD per 2-mm(2) area, 476 +/- 136 and 224 +/- 133; P<.01). Postmenopausal ovaries with or without hyperthecosis had the highest density of nerve fibers. In cyclic and polycystic ovaries, more tryptase-positive mast cells than chymase-positive mast cells were found in the interstitial cortex and the medulla. In cyclic ovaries, areas with a moderate density of nerve fibers contained many mast cells. Hence, with increasing nerve fiber density in polycystic ovaries, the number of mast cells decreased strikingly compared with cyclic ovaries (p<.001). Almost no mast cells were seen in postmenopausal ovaries with and without hyperthecosis. The number of leukocyte antigen-positive leukocytes was similar in all groups. CONCLUSION(S): The high density of nerve fibers in polycystic and postmenopausal ovaries, together with a conspicuous decrease in mast cells, indicates altered neuroimmune communication.

Aged↗

Long-term expression of heme oxygenase-1 (HO-1, HSP-32) following focal cerebral infarctions and traumatic brain injury in humans.

Extracellular heme derived from hemoglobin following hemorrhage or released from dying cells induces the expression of heme oxygenase-1 (HO-1, HSP-32) which metabolizes heme to the gaseous mediator carbon monoxide (CO), iron (Fe) and biliverdin. Biliverdin and its product bilirubin are powerful antioxidants. Thus, expression of HO-1 is considered to be a protective mechanism against oxidative stress and has been described in microglia, astrocytes and neurons following distinct experimental models of pathological alterations to the brain such as subarachnoidal hemorrhage, ischemia and traumatic brain injury (TBI) and in human neurodegenerative diseases. We have now analyzed the expression of HO-1 in human brains following TBI (n = 28; survival times: few minutes up to 6 months) and focal cerebral infarctions (FCI; n = 17; survival time: < 1 day up to months) by immunohistochemistry. Follwing TBI, accumulation of HO-1+ microglia/macrophages at the hemorrhagic lesion was detected as early as 6 h post trauma and was still pronounced after 6 months. In contrast, after FCI HO-1+ microglia/macrophages accumulated within focal hemorrhages only and were absent in non-hemorrhagic regions. Further, HO-1 was weakly expressed in astrocytes in the perifocal penumbra. In contrast to experimental data derived from rat focal ischemia, these results indicate a prolonged HO-1 expression in humans after brain injury.

Adolescent↗

Lesion-associated accumulation of uPAR/CD87- expressing infiltrating granulocytes, activated microglial cells/macrophages and upregulation by endothelial cells following TBI and FCI in humans.

Urokinase-type plasminogen activator receptor (uPAR/CD87) together with its ligand, urokinase-type plasminogen activator (uPA), constitutes a proteolytic system associated with tissue remodelling and leucocyte infiltration. uPAR is a member of the glycosyl phosphatidyl inositol (GPI) anchored protein family. The functional role of uPAR comprises fibrinolysis by conversion of plasminogen to plasmin. In addition, uPAR promotes cell adhesion, migration, proliferation, re-organization of the actin cytoskeleton, and angiogenesis. Furthermore, uPAR is involved in prevention of scar formation and is chemoattractant to macrophages and leucocytes. In order to investigate the pathophysiological role of uPAR following human CNS injury we examined necrotic brain lesions resulting from traumatic brain injury (TBI; n = 28) and focal cerebral infarctions (FCI; n = 17) by immunohistochemistry. Numbers of uPAR+ cells and uPAR+ blood vessels were counted. Following brain damage, uPAR+ cells increased significantly within 12 h, reached a maximum after 3-4 days and remained elevated until later stages. uPAR was expressed by infiltrating granulocytes, activated microglia/macrophages and endothelial cells. Numbers of uPAR+ vessels increased in parallel subsiding earlier following FCI than post TBI. The restricted, lesion-associated accumulation of uPAR+ cells in the brain parenchyma and upregulated expression by endothelial cells suggests a crucial role for the influx of inflammatory cells and blood-brain barrier (BBB) disturbance. Through a failure in BBB function, uPAR participates in formation of brain oedema and thus contributes to secondary brain damage. In conclusion, the study defines the localization, kinetic course and cellular source of uPAR as a potential pharmacological target following human TBI and FCI.

Adolescent↗

Pontine axonal injury after brain trauma and nontraumatic hypoxic-ischemic brain damage.

Experimental studies have shown that diffuse axonal injury is usually induced by positive or negative acceleration mechanisms. In order to determine the reliability of axonal injury (AI) as a marker of this type of traumatic insult, we compared cases of trauma-induced focal cortical hemorrhage without dural involvement (n = 67) with cases of trauma-induced subdural bleeding without cortical hemorrhage (n = 26). Both groups exhibited a wide range of post-traumatic survival times. The injuries in the first group were caused mainly by direct impact to the head, those in the second by acceleration/deceleration mechanisms. The investigations were based primarily on immunohistochemical demonstration of antibodies targeted to beta-amyloid precursor protein (beta-APP) in the pons as a marker of AI and the results were assessed semiquantitatively. No significant differences were found between the two groups. In both groups AI was detected in 80-100% of cases with survival times of more than 3 h and two thirds of all positive cases showed pronounced positivity. Additional comparison of cases of brain death due to mechanical trauma (n = 14) with cases of brain death due to non-mechanical trauma (n = 18) also disclosed no significant intergroup differences. Finally, investigations of the pons in cases of non-traumatic death due to cerebral hypoxia/ischemia (n = 51) demonstrated AI with the same frequency as in the other groups, although the expression tended to be less pronounced. Our results confirm that beta-APP expression in the pons is a reliable indicator of AI but does not discriminate between injuries caused by traumatic strain or shearing mechanisms and secondary damage due to cerebral hypoxia/ischemia or edema. In the large majority of cases with prolonged post-traumatic survival, it can therefore be assumed that AI in the pons is the consequence of primary and/or secondary events or a combination of both, as is common in non-missile head injury survived for more than 90-120 min. Therefore, positive differentiation of the type of biomechanical event based on this criterion alone is not possible.

Adolescent↗

Axonal injury--a diagnostic tool in forensic neuropathology? A review.

We used beta-amyloid precursor protein (beta-APP) to investigate our own forensic neuropathological case material (n = 252) in light of the current literature on the phenomenon "axonal injury" (AI) to determine the incidence, specificity and biomechanical significance of AI and its significance for determining vitality and survival time. The case material consisted of cases of fatal nonmissile closed-head injury (n = 119), gunshot injury (n = 30), fatal cerebral ischemia/hypoxia (n = 51), brain death caused by mechanical trauma (n = 14) or nonmechanical injury (n = 18), and acute hemorrhagic shock (n = 20). AI was observed in 65% to 100% of cases of closed-head injury, fatal cerebral ischemia/hypoxia, and brain death with a survival time of more than 3 h; AI could not be detected in the cases of acute hemorrhagic shock. A statistically significant difference between traumatically and nontraumatically induced (nondisruptive) AI was not found. There was no statistical evidence of a correlation between AI and the different types of external force, since AI could be demonstrated after both acceleration/deceleration injuries and traumatic impact. Therefore, biomechanical inferences for reconstruction purposes are not possible. On the other hand, beta-APP was found to be a definite marker of vitality. In our material, cases with a posttraumatic interval of under 180 min did not express beta-APP. Moreover, the literature shows that the posttraumatic interval can be determined by other methods for demonstration of AI such as by ubiquitin immunostaining (360 min), silver staining (15-18 h), hematoxylin and eosin staining (about 24 h), or by demonstration of a microglial reaction (about 4 to 10 days) or of a few remaining isolated bulbs, without accompanying fibers, which can be detected after a survival time of up to 17 months.

Adolescent↗

Insulin injection sites: morphology and immunohistochemistry.

In a case of insulin suicide in a nondiabetic woman, insulin was detected in routinely formalin fixed and paraffin embedded subcutaneous injection marks, in spite of a post-morterm interval of 24 days. Around birefringent crystalline material, probably zinc phosphate, immunohistochemistry revealed granular insulin depots as well as an insulin staining along the lipocyte membranes. A cellular reaction of granulocytic character was present, with an uptake of insulin by inflammatory cells.

Autopsy↗

ABH and Lewis immunohistochemistry of the human eye.

ABH and Lewis antigens are detected by immunohistochemistry exclusively in the anterior cornea epithelium and in the conjunctiva bulbi, but not in the ciliary body, in the retina, or in the vitreous body of the eye. The ABH antigens found in the vitreous humor by the absorption elution technique (Rordorf et al., Forensic Sci. Int. 41, 1989, 111-116) are probably glycosphingolipids, which are not detected by immunohistochemistry. They may come from the plasma of uveal blood vessels, or be produced by local cells.

ABO Blood-Group System↗

Characterization of bile ducts in primary biliary cirrhosis and other liver diseases by immunohistochemical demonstration of Lewis(a) or b antigen.

We investigated Lewis(a) and Lewis(b) expression of bile ducts in 68 specimens from various kinds of liver disease. In addition, the number of IgM and IgG synthesizing plasma cells in the hepatic inflammatory reactions were immunostained and counted. We found a statistically significant decrease in the number of bile ducts in PBC (primary biliary cirrhosis) in comparison with either chronic active or persistent hepatitis (CAH/CPH). Bile ducts could be detected easily and constantly by their Lewis antigen expression. Isolated bile duct epithelial cells not apparent in H&E sections could be identified by Lewis(a) and b immunostaining. The number of plasma cells in PBC was significantly different than in (CAH/CPH). A large number of IgM plasma cells was a characteristic feature of PBC. However, neither counting of Lewis(a) and b positive bile ducts nor counting of IgM plasma cells was of definite diagnostic significance in the individual clinical case, since no cut-off value could be determined above or below which a PBC was ruled out or proven.

Bile Ducts↗

[Sudden cardiac death in childhood due to and abnormal origin of the coronary arteries].

A seven-year-old girl suddenly collapsed during a sports session at school. An orthostatic syndrome was assumed. In the next two-and-a-half years she experienced four further attacks of weakness with vertigo and vomiting. Paediatric cardiological examination found her to be below the 3rd percentile for height, but the other physical findings and a thoracic radiogram were according to her age. The resting ECG showed increased T waves in V5 and V6, interpreted as signs of vagotonia. Echocardiography was normal, the results of the Schellong test suggested abnormal hypotonic circulatory regulation. Five months later the girl died suddenly after physical exertion. The post-mortem revealed anomalous origin of the left coronary artery (LCA) with a slit-like ostium from the right sinus of Valsalva. The very narrow initial part of the LCA passed tangentially through the wall of the aortic root and then took a leftward course between the aortic root and the pulmonary trunk.--It is assumed that the sudden cardiac death resulted from compression of the intramural segment of the LCA.

Autopsy↗

Cathepsin D as a vitality marker in human skin wounds.

This paper shows the results obtained by studying the lysosomal enzyme Cathepsin D as a potential marker for the vitality of wounds in human specimens. We have analyzed 53 samples using enzymological and histological techniques. Our results show the ability of Cathepsin D to establish the vital origin of wounds inflicted 5 minutes or less before death, where the specific activity of cathepsin D reached 0.055 units at the wound edge and 0.01 units in their respective controls (P < 0.001). As previously demonstrated in an experimental series, Cathepsin D seems to be a very useful marker of high forensic interest in especially difficult cases. Further studies are in progress to check the influence of different factors such as drugs intake and clinical conditions on Cathepsin D activity.

Adolescent↗

[Increased ethanol elimination after barium meal--human experimental study with parenteral alcohol administration].

The results of human experimental investigations of blood alcohol kinetics in intravenous alcohol administration published in recent years suggest that alterations both of the current ADH activity and of the rate of hepatic blood flow affect the excretion. The effects of a voluminous gastrointestinal load of 500 g of inert BaSO4 definitively free of calories on the elimination kinetics of ethanol are investigated in two groups each comprising five male subjects. The alcohol is administered exclusively parenterally. Peak blood alcohol values between 0.5 and 1.1 per thousand are attained. After a barium meal, the elimination is significantly raised (p less than 0.01; p less than 0.05) in both groups. The rate of increase up to 27 percent of the baseline value (beta 60 min. 0.108; beta 60 max. 0.15 g/kg) is attributed to the raised hepatic blood flow.

Administration, Oral↗

Diagnostic significance of myofibrillar degeneration of cardiocytes in forensic pathology.

The incidence of myofibrillar degeneration (MFD) was studied in the following different forensic-pathological diagnostic groups of 25 cases each: acute morphine intoxication, acute carbon monoxide intoxication, hanging, strangulation by hand/ligature, drowning, acute hemorrhagic shock, lethal acute brain injury, explainable death of babies or infants and sudden infant death syndrome, together with 18 cases of intoxication with various drugs. The MFD was demonstrated by the Luxol-fast-blue reaction, with two types of phenomena being differentiated, namely cross-band lesions and diffuse staining. All diagnostic groups included cases of MFD of differing degrees. Cross-band lesions were observed in practically all cases of hanging, strangulation and acute hemorrhagic shock. Diffuse stain was noted particularly in cases of drowning and acute brain injury. The diagnostic significance is discussed.

Acute Disease↗

[Myofibril degeneration of heart muscle: histologic picture and pathophysiologic significance].

Mechanical trauma to the heart induces a rhythmical transverse banding of adjacent myocytes. This finding is due to hypercontraction (true contraction bands) and it is different from the cross band type myofibrillar degeneration (MFD) which is characterized by disseminated foci of irregular transverse banding. This latter type is mainly found after temporary myocardial ischemia, in cases of reanimation using catecholamines and defibrillation as well as in severe brain trauma. Both types of cross banding can be identified in hematoxylin and eosin or in azan stains; a much better visualization is obtained using the PTAH or the Luxol Fast Blue (LBF) method. Moreover, LFB, giving a selective blue staining of the damaged cells, allows the identification of the recently described diffuse type MFD. Well developed contraction bands may indicate the vitality of a heart trauma, yet a supravital occurrence seems to be possible. MFD, diffuse or cross band type, clearly correlates with high blood catecholamine levels at the time of death.

Cardiomyopathies↗

[Myofibril degeneration of heart muscle: diagnostic value of selected forensic pathology case material].

Information on the incidence of myofibrillary degeneration (MFD) was obtained by investigating the hearts of seven groups of cases with different forensic diagnosis using luxol fast blue as a staining method. The following diagnostic groups were examined: acute morphine intoxication, acute carbon monoxide intoxication, hanging, strangling by hand and/or ligature, drowning, acute hemorrhagic shock and sudden infant death syndrome. MFD positive cases were found in all diagnostic groups, but the morphologic expression of MFD as well the number of cases per group differed: The phenomenon of cytoplasmatic banding could be observed in nearly all cases of hanging, strangling and acute hemorrhagic shock; the phenomenon of diffuse cytoplasmatic staining in most cases of drowning. The diagnostic importance is discussed.

Adult↗