Pharmacokinetic features in forensic medicine.

As a rule, the concentration curves of substances in various body volumes, in particular in plasma and blood volume, can be reproduced by a number of exponentional functions. A compartment system can be isomorphically assigned to such a representation in which a mass exchange takes place between the constituent volumes. In forensic medicine (toxicology), the "central compartment model" is used in which an exchange of substances between the blood space (central compartment) and the peripheral spaces (peripheral compartments) takes place. Characteristic parameters of the compartment models are their volumes and the intercompartmental mass flows or their rate constants. They can be determined from the mathematical representations of the concentration curves. It is possible to obtain knowledge on the properties (e.g. permeability) of the convectional/diffusional transcapillary transport on the basis of these parameters.

Iatrogenically-related, fatal methotrexate intoxication: a series of four cases.

Since the early eighties, the folic antagonist methotrexate (MTX) has been used in long-term treatment of rheumatoid arthritis. Because of the high toxic potential clinical and laboratory controls at regular intervals and patient education in order to avoid misadventure is of overriding importance. We present four cases of fatal MTX intoxication due to medical malpractice from the Tübingen Institute of Forensic Medicine autopsy material, which show the severe consequences of MTX overdose. It becomes evident that among non-rheumatologists there still is need for information about toxicity and dose limitation in MTX low-dose treatment.

Ninhydrin-dyed latent fingerprints as a DNA source in a murder case.

In this case report, we describe the possibility of using ninhydrin-dyed fingerprints as a DNA source for STR typing. Preliminary tests prove that ninhydrin-dyed material still can be useful for STR typing. The case material consisted of seven ninhydrin-labeled latent fingerprints found at a murder crime site, which could not be typed in a classical manner. We were able to swap DNA from the ninhydrin-treated areas and successfully use it for STR typing.

[Gunshot reconstructions based on individually parametrical 3-dimensional victim models]. / Schussrekonstruktionen anhand individuell parametrisierbarer dreidimensionaler Opfermodelle.

In cases of lethal firearm injuries computer enhanced anatomical feasibility studies can provide unambiguous clues concerning self-versus extraneous infliction. To this end individualized digital 3-dimensional geometrical models of the victim and the weapon are generated true to scale with the help of the CAD software (POSER Version 4, egi.sys AG). All anatomical data relevant to the motion apparatus and the range of movement as well as the injuries of the individual victim are carefully documented and serve as input parameters for the digital geometrical model. The bullet path is visualized as a cylinder between entrance and exit wound. A series of simulation sequences then can be carried out by the variation of anatomically possible shot positions and the virtual grasp of the weapon. An exact alignment of the firearm's barrel and the bullet path is a reliable statement for the feasibility of self-infliction. In addition to circumstantial evidence the digital reconstruction of the firearm shot admits of unambiguous conclusions about the course of the traumatic event.

Delimitation of the time of death by immunohistochemical detection of calcitonin.

To improve the possibilities of delimitating the time of death after longer laytime it was examined if this is possible by immunohistochemical detection of calcitonin. The results show that in our examination material the c-cells of the thyroid glands of up to 4-day-old corpses produce a positive immunoreaction towards calcitonin in all cases whereas none of the corpses older than 13 days show such a reaction. This means that in the case of a negative immunoreaction the time of death can be assumed to lie >4 days before the autopsy. The fact that a negative immunoreaction occurred consistently after 13 days leads to the conclusion that when calcitonin has been stained in a specimen, the death of the respective person must lie a maximum of 12 days earlier, whereby these time-limits may change in considerably different surrounding conditions.

Delimitation of the time of death by immunohistochemical detection of glucagon in pancreatic alpha-cells.

To improve the possibilities of delimitating the time of death after longer laytime it was examined if this is possible by immunohistochemical glucagon detection. The results show that in our examination material the pancreatic alpha-cells of up to 6-day-old corpses produce a positive immunoreaction towards glucagon in all cases whereas none of the corpses older than 14 days show such a reaction. This means that in the case of a negative immunoreaction the time of death can be assumed to lie more than 7 days before the autopsy. The fact that a negative immunoreaction occurs consistently after 14 days leads to the conclusion that when glucagon has been stained in a specimen, the death of the respective person must lie a maximum of 13 days earlier, whereby under markedly different conditions to the ones of the cases here examined, a negative immunoreaction could happen earlier and a positive immunoreaction even later.

Streifenlichttopometrie (SLT): a new method for the three-dimensional photorealistic forensic documentation in colour.

By means of the new method of Streifenlichttopometrie (SLT) it is possible to record the complete body surface of casualties in a practically photorealistic fashion, i.e. three-dimensionally and in colour. In comparison with the classic method of Photogrammetry Streifenlichttopometrie (SLT) is remarkably faster (10,000 points/s instead of 1 point/s) and in addition the colour of every point measured upon the corpse's surface is instantly recorded. Taking into consideration the resolution required and the qualities of the camera system the body surface is recorded in 'patches', i.e., areas of a defined extension (in the present case 500 mmx500 mmx200 mm) which are marked with a body fixed reference frame to grant the exact matching of the data after the recording process. Length, perimeter, square and volume of the body segments and injuries can be determined. Furthermore the natural colour of the wounds can be used for an immediate classification according to the intensity of the impact forces. In addition the 3-D coordinates of the body surface including the wounds can be transferred into an animated computer simulation for the reconstruction of the traumatic events.

Dynamics of microglial activation after human traumatic brain injury are revealed by delayed expression of macrophage-related proteins MRP8 and MRP14.

Human traumatic brain injury (TBI) is ideally suited for investigation of the kinetics of human microglial cell activation as the onset of lesion formation is precisely defined. The present study provides evidence of a distinct delay in macrophage/microglia response following TBI. Eighteen brains of patients who had survived TBI for 1 h to 6 months were analysed by immunohistology. Samples of contusional and non-contusional areas were studied using antibodies directed against antigens of microglia/ macrophages [major histocompatibility complex class II, CD4, interleukin (IL)-16, macrophage-related protein (MRP) 8 and MRP14]. IL-16, a natural ligand to CD4, was expressed constitutively by numerous microglial cells in all cases throughout the brain. CD4 could be detected regularly on perivascular cells. MRP8 and MRP14, which are only expressed on activated macrophages and microglial cells, could be detected only within brains with a survival time of more than 72 h post TBI. In addition, proliferation of microglia detected by MIB-1 was not present until 72 h. This delayed expression of the activation markers MRP8 and MRP14 and the proliferation marker MIB-1 is comparable to experimental closed head injuries but strictly different from acute activation found in ischemic brains.

Delimitation of the time of death by immunohistochemical detection of thyroglobulin.

To improve the possibilities to delimit the time of death after longer laytime it was examined if this is possible by immunohistochemical detection of thyroglobulin. The results show that in our examination material the colloid and the follicular cells of the thyroid glands of up to 5-day-old corpses produce a positive immunoreaction towards thyroglobulin in all cases whereas none of the corpses older than 13 days show such a reaction. This means that in case of a negative immunoreaction the time of death can be assumed to lie more than 6 days before the autopsy. The fact that a negative immunoreaction occurs consistently after 13 days leads to the conclusion that when thyroglobulin has been stained in a specimen, the death of the respective person must lie a maximum of 12 days earlier, whereby these time-limits may change in considerably different surrounding conditions.

Demonstration of morphine in ganglion cells of the hippocampus from victims of heroin overdose by means of anti-morphine antiserum.

To investigate the topography of morphine distribution in the human brain, a method has been developed to detect morphine immunohistochemically. In this study hippocampus tissue from victims of heroin overdose (blood morphine concentrations 220 ng/g-1500 ng/g; 6-MAM positive urine sample), known for its high concentration of mu-opiate receptors was used. The immunohistochemical staining was performed with an anti-morphine antiserum originally developed for radio-immunoassays. In comparison with control specimens from cases of sudden death without morphine exposition or a history of heroin abuse, the brains from victims of heroin overdose showed selectively stained ganglion cells, axons and dendrites, suggesting a massive concentration of morphine in the neuronal structures.

Frequent D-loop polymorphism in mtDNA enables genotyping of 1400-year-old human remains from Merowingian graves.

Improvements of DNA extraction and amplification techniques presently enable DNA analysis of ancient DNA (aDNA) from samples which range from several hundred years of age up to possibly 5000 years. Taking advantage of the abundance of mitochondrial DNA and its polymorphic D-loop sequence, ten individuals from multiple burial sites of the Merowingian culture (South Germany), estimated to be about 1400 years old, were genotyped to determine possible kinship. Moreover, gonosomal DNA markers from the X- and Y-chromosome were applied for sex determination of the remains. In all individuals investigated, deviations from the Anderson mtDNA consensus sequence were observed, all representing substitutions (7 transitions and 3 transversions). Although such mutations have been reported from recent populations, our study constitutes the first description of these mtDNA mutations from numerous aDNA samples recovered from multiple burial sites. The results obtained by molecular anthropology can aid in describing kinship relations and burial customs of ancient remains.

Percentile charts to determine the duration of child abuse by chronic malnutrition.

Longstanding quantitative or qualitative under-supply of nutrition leads to weight loss and, in children, to stagnation of growth and thus to stunted growth. A comparison of the expected growth, according to percentile growth curves, with the actual body size, gives an indication as to the period of time in which malnutrition took place. The moment in which the growth curve bends off and leaves the norm is to be interpreted as the earliest begin, the moment in which the attained growth would have been achieved as the latest begin of the nutritional impairment.

Delimitation of the time of death by immunohistochemical detection of insulin in pancreatic beta-cells.

To improve the possibilities to delimitate the time of death after longer laytime, it was examined if this is possible by immunohistochemical insulin detection. The results show that in our examination material, the pancreatic beta-cells of up to 12-day-old corpses produce a positive immunoreaction towards insulin in all cases, whereas none of the corpses older than 30 days show such a reaction. This means that in case of a negative immunoreaction, the time of death can be assumed to lie more than 12 days before the autopsy. The fact that a negative immunoreaction occurs consistently after 30 days leads to the conclusion that when insulin has been stained in a specimen, the death of the respective person must lie a maximum of 29 days earlier, whereby these time-limits may change in considerably different surrounding conditions.

Insulin- or morphine-injection? Immunohistochemical contribution to the elucidation of a case.

Two autopsy cases of an elderly couple who died on the same day will be used to underline the importance of immunohistochemistry of forensic practice. At first unexplainable injection marks on the upper arms of the corpses and the possibility of a closely related physician injecting insulin and certifying a natural death made it important, considering suspect insulin concentrations in the blood, to exclude insulin injections in these marks. Further, the statement that morphine had been injected for the analgesia of tumour pains, was reinforced by immunohistochemistry.

[Immunohistochemical insulin evidence at the injection site]. / Immunhistochemischer Insulinnachweis an der Injektionsstelle.

Under suspicion on an injection of high doses of insulin with suicidal or homicidal intention, the local detection of a vital injection of insulin is necessary for the critical examination. The submitted immunohistochemical method shows, that: the insulin-specific positive immunoreaction of the subcutaneous fatty tissue is assigned to an injection of insulin, although a missing staining does not exclude a premortal application of insulin, a widened immunopositive intercellular space between the subcutaneous lipocytes as expression of a local edema points to the intravitality of the injection of insulin.

[Ocular pathology of child abuse]. / Okuläre Pathologie der Kindesmisshandlung.

BACKGROUND: In spite of a growing awareness in the population most cases of child abuse remain probably undetected. Ocular changes in this syndrome are manifold. Sometimes ocular signs can help to substantiate the suspicion of child abuse. On the other hand the ophthalmologist may be the first physician to be contacted. Thus, he plays an important role in diagnosis. Though there are a couple of clinical descriptions morphological data are almost completely missing in the German literature. PATIENT: A two-year-old girl died two days after severe abuse because of widespread intracranial hemorrhages with brain stem insufficiency. At autopsy both eyes were enucleated and sent for histological investigation. RESULTS: The anterior segments were unremarkable. Multiple hemorrhages were found in the inner retina bilaterally. Moreover there were preretinal, intrachoroidal, intrascleral (area of the circle of Zinn-Haller) and subdural hemorrhages. One eye showed a circular, perimacular fold of the central retina and a hemorrhagic retinoschisis. CONCLUSIONS: Intraretinal hemorrhages alone are typical though not pathognomonic for the "battered-child syndrome". However, in combination with a crater-like appearance of the central retina, a hemorrhagic retinoschisis; and intrascleral hemorrhages in the area of the circle of Zinn-Haller they suggest child abuse almost with certainty. The pathogenic mechanisms leading to the observed fundus changes lack definite clarification. The date of violence which is essential for legal prosecution can be difficult to evaluate on morphological grounds alone.

[Concentration dependent ethanol metabolism in steady-state]. / Konzentrationsabhängigkeit der Ethanolumsatzraten im steady-state.

Ethanol infusion rates necessary to maintain steady-state ethanol concentrations are dependent on the actual ethanol concentration in a monotonous increasing manner.

Expression of microglial markers in the human CNS after closed head injury.

The loss of neurons after severe closed head injury is not only a consequence of the primary impact but also of secondary damage mechanisms. Among the cell population of the central nervous system microglia is surely a candidate to influence secondary damage mechanisms by releasing cytotoxic cytokines [1]. About microglial reaction in closed traumatic brain injury (TBI), however, no data are available. In contrast to experiments using stab wound injury the covering of the CNS in closed TBI are still intact. We have examined 17 patients who died because of TBI after various times post injury. We studied the expression of antigens which are either permanently present on microglial cells or those which are only facultatively found on activated microglia. Low numbers of microglial cells were shown to express MHC-class II antigens immediately after TBI which is also true for CD 68 and leukocyte common antigen (LCA). Surprisingly, however, antigens such as HAM 56 were expressed not earlier than 72 hours after TBI as well as the lectin ricinus communis agglutinin-1 (RCA-1). The results indicate a delayed activation of microglia in traumatic brain injury.

[Rate of ethanol clearance after oral and parenteral ethanol administration]. / Die Ethanol-Konzentrationsabfallraten nach oraler und nach parenteraler Ethanolapplikation.

A crossover investigation of the ethanol concentration decline after oral and parenteral administration of ethanol respectively was performed with direct intra- and interindividual comparison. No significant differences in relation to the kind of administration were noted. An influence of the circadian rhythm on the rate of decline could be excluded. The low beta 60 values derived (average: 0.111 g/kg/h) can be explained by the long period over which the probands were denied food.