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Biomedical subjects

R Mattern

Publications and source records attributed to R Mattern.

At least 19 recordsLinked to original sources

A preliminary study on the stability of benzodiazepines in blood and plasma stored at 4 degrees C.

An approach to determine the stability of benzodiazepines and some of their metabolites (n = 13) by means of a routinely applied gas chromatographic method using electron capture detection was made in this preliminary study. Validation data of the method are given. Spiked blood and plasma samples were stored at 4 degrees C and analysed at selected times up to 240 days. The concentrations of all analytes had decreased to at least 60% of the original levels at the end of the observation period. A clear pattern of breakdown could not be established. The data obtained suggest that results from long-term stored samples should be interpreted cautiously. Further investigations concerning the stability of drugs in blood and plasma samples, additional methods of identification and determination as well as the establishment of optimal storage conditions seem necessary.

Benzodiazepines

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

[Biomechanics of combined Kirschner wire osteosynthesis in the human model of unstable dorsal, distal radius fractures (Colles type)].

In an experimental study, the biomechanical qualities of the combined Kirschner wire osteosynthesis (KWO) in the unstable Colles' fracture were analyzed. This type of pin fixation is our preferred osteosynthesis in the treatment of unstable Colles' fracture because it allows immediate functional therapy. It represents a modification of Kapandji's dynamic KWO, compensating for the insufficient volar stability by means of the conventional static KWO. Clinical experience according to the anatomical and functional results, was very encouraging suggesting that a clinical concept based on the biomechanical principles of combined KWO and its single components should be constituted. Simulation of the unstable Colles' fracture was realized by dorsal wedge osteotomy of the distal end of the radius using cadaveric material. This fracture model was subsequently pinned using the different KWO types and tested by a standardized vector energy testing device regarding its stability in the four main loading directions. The combined KWO unifies the advantage of volar stability of the conventional KWO with the high dorsal stability of dynamic KWO. The main functional principle of dynamic KWO with regard to its axial stability consists in the repositioning of the dorsal bone fragmentation zone and hence the reconstitution of cortical load transmission. Besides its good stabilization, dynamic KWO also leads to optimal alignment of the distal metaphyseal fragment. Furthermore, the experiments yielded important information about technical aspects of the surgical procedure, which helps us to avoid anatomical and functional deficiencies. Based on these experimental findings, the surgical technique of combined KWO was standardized.

Biomechanical Phenomena

An in vitro experiment for postmortem vascular permeation. The passage of morphine and morphine glucuronides across a vascular wall.

A venous blood sample taken at autopsy cannot be considered to represent the antemortem blood concentration of a particular substance. Autolytic processes cause disintegration and increasing permeability of the physiological and anatomical barriers such as vascular walls and lead to changes in substance concentrations. In the present study, the experimental design represents an in vitro postmortem simulation of a drug substance crossing a venous wall. The postmortem behavior of morphine, morphine-3- and morphine-6-glucuronide was investigated. A Chien-Valia-diffusion chamber with a patch of inferior vena cava as diffusion barrier was used. For optimal simulation of postmortem events, vein sampling was restricted to selected autopsy cases. Parameters for the analysis of diffusion across the vascular tissue were dependence on time, temperature, and initial substance concentrations. The penetration behavior simulating venous efflux and influx of the substances was studied by different orientation of the venous wall in the experiments. Rhodamine B was used as a model substance to visualize the binding to the tissue and the passage across the venous wall. The permeation of morphine, morphine-3- and morphine-6-glucuronide across a vein tissue was found to be mainly dependent on the disintegration of the vascular wall and on the postmortem time period as well as on concentration gradients. From the data of this preliminary in vitro study, it can be concluded that a lag time for transvascular diffusion exists postmortem. However, it could be demonstrated, that adsorption to and penetration into the vascular tissue may alter intraluminal blood concentrations even at an early stage of the postmortem time period.

Biological Transport

Estimation of sex on the basis of radiographs of the calcaneus.

Lateral and anteroposterior radiographs of the ankles of 800 Central Europeans aged 20 to 79 were analyzed with regard to sexual dimorphism. All the distances, but not the angles, of the calcaneus were much larger in males than in females. Approximately 80% of the study sample could be sexed correctly by classifying all specimens greater than 86.0 mm in length as male and those less than 86.0 mm as female. The prevalence of os tibiale externum was 8.0 and 2.6% and the prevalence of plantar heel spur was 16.3 and 6.5% (increasing with age) for males and females, respectively, being significantly more frequent in females. On the other hand, the bone island frequencies were 9.1% in males and 4.8% in females. Our study suggests that radiographs of the ankle are a convenient, rapid, cheap and non-invasive means for estimating sex.

Adult

Postmortem distribution pattern of morphine and morphine glucuronides in heroin overdose.

The postmortem distribution of morphine and its metabolites was investigated in four cases of heroin overdose to evaluate some of the factors that influence intravasal blood concentrations. Variables included were the chemical stability of morphine conjugates, hemoconcentration, incomplete distribution of the drug and diffusion processes. Blood samples from different sampling sites including the aorta, the infra- and suprarenal portion of the inferior vena cava, the superior vena cava, the femoral and subclavian veins, and the right and left ventricles were examined for morphine, morphine-3-glucuronide and morphine-6-glucuronide, hematocrit and water content. Drug concentrations were determined by HPLC based on the native fluorescence of the analytes. Morphine glucuronides proved to be stable for a time period of 72 h. The water content ranged from 65 to 83% and hematocrit values from 25 to 75%, and were seen as contributory factors to the dramatic differences observed for drug concentrations from different sampling sites. The differences could neither be attributed to incomplete distribution during life-time nor to a diffusion process following the different distribution volumes of morphine and its conjugates. A definite relationship between the ratio of the molar concentrations of morphine and its glucuronides, as assessed in pharmacokinetical studies after morphine dosing, could not be established. For a better understanding more cases and changes over time and tissue concentrations should be analysed.

Adult

[The incidence, age dependence and sex distribution of the calcaneal spur. An analysis of its x-ray morphology in 1027 patients of the central European population].

In 1027 lateral radiograms of the ankle in a Caucasian population, 161 plantar and/or dorsal calcaneal spurs (15.7%) were diagnosed. Plantar spurs were more common than dorsal spurs (11.2 and 9.3% respectively). Prevalence of both spurs increases considerably with the rising age. Dorsal spurs appear slightly earlier than plantar spurs. The spur frequencies are similar in left and right feet. The plantar spurs were significantly (p < 0.0001) more common in women than in men in general, while dorsal spurs were more frequent in men than in women up to the age of 70. The previously reported higher frequencies of plantar and dorsal calcaneal spurs in women than in men are probably a result of a disproportionally higher number of women in higher age in the groups studied. In forensic medicine, calcaneal spurs provide evidence for identity and age of unknown corpses, and to certain extend their profession, physical activities and constitution during life.

Adolescent

[Congener analysis in a drinking trial with unusually high alcohol content].

The aforementioned case proves very convincingly that a very high dose of alcohol consumed within a short time span can be absorbed completely within 2 hours. Numerical models based on low to moderate alcohol consumption were lower than expected in cases of severe alcohol intake. The claim of alcohol consumption after an event can best be verified by means of a drinking experiment under intensive medical supervision.

Accidents, Traffic

[Life threatening complications in alternative medicine--problems in patient education].

The risk of treatment offered by nonmedical practitioners are demonstrated with six casuistic expertise reports. In four cases the treatment had a lethal outcome, because the underlying illnesses had been underestimated or had not been diagnosed. To the authors opinion a patient's consent in a treatment by nonmedical practitioners is inoperative, because a nonmedical practitioner is on principle unable to inform a patient regularly because of his lack of medical knowledge.

Adult

[Cell therapy and its risks].

Parenteral administration of fresh cells, frozen cells (snapfrozen cell suspensions) or lyophilized cells (sicca cells), is known as cellular or cell therapy. While the German Health Office (BGA) provisionally banned the use of dried cell preparations in 1987, injection of fresh cells is still allowed. There have been repeated reports of life-threatening, and even fatal, complications of this type of therapy. Since it involves the administration of heterologous biological material, most of the complications that have been observed have been of the allergic/hyperergic type resembling experimental allergic encephalomyelitis (EAE) and experimental allergic neuritis (EAN). When evaluating the risks of this form of alternative-medical treatment, the well-known risks of injection therapy must also be borne in mind. In the case of cell therapy, too, the hoped for effect must be weighed against the risks of the procedure, and our guiding principle must be: nil nocere.

Cell- and Tissue-Based Therapy

Diseases of the vertebral arteries.

Case reports and postmortem neuropathological findings of a wide spectrum of diseases affecting the vertebral arteries, in particular vasculitis, traumatic lesions, degenerative changes and congenital abnormalities, are discussed.

Adult

Quantitative and qualitative analysis of DNA extracted from postmortem muscle tissues.

DNA extracted from 33 postmortem muscle specimens was analyzed using MZ 1.3, a hypervariable minisatellite probe, as well as locus-specific minisatellite probes (g3, MS1 and MS43). After storage at -25 degrees C for 10 months, DNA from all the samples was partially (approximately 21% of total DNA) degraded even when autopsy was performed 1 day postmortem. However, more than 90% of DNA samples up to at least 3 days postmortem were suitable to obtain good restriction fragment length polymorphism (RFLP) patterns. When small strips of specimen were stored for 8 days at room temperature in moist chambers, approximately 42% of total DNA was degraded. Only 30% of these DNA samples still showed good RFLP patterns. However, no obvious relation between qualities of DNA analyzed by detection of RFLP and quantities of total and high-MW DNA became apparent. A case of familial relationship was ascertained by DNA fingerprints. Since DNA of good quality can be recovered from muscle tissues in large quantities, DNA extraction from muscle tissues and detection of RFLP patterns should be very useful for individual identification in autopsy cases.

Accidents, Aviation

[Expert systems in forensic medicine. Pilot project in the differential diagnosis of death caused by hanging].

The special field of legal medicine represents a very heterogeneous science, which makes it impossible, that a forensic pathologist could be an "expert" in all areas. The most recent achievements of computer-technology have opened up the possibility of being able to use a PC to produce an "expert system", for with large computer programs are needed. Therefore we wanted to test in a pilot project, if it was possible to establish an expert system, which was suitable for supporting forensic pathological diagnosis. We confined ourselves to the differential diagnosis of "death by hanging" where a clear line between vital and postmortal events, respectively suicide, homicide and accident was drawn. The discrepancy between the relatively scanty amount of statistically reliable data on the one hand and the complexity of the manifestation of death by hanging on the other hand proved to be the main problem. Although we are not yet able to make an expert system available which meets all our requirements, we are convinced, that in the future computer-aided diagnosis may be of great use for work in legal medicine.

Accidents

[Complications following cell therapy].

So far, the law in the Federal Republic of Germany still allows the injection of fresh-cell preparations from animals as a roborant to increase the vitality of the organism and to strengthen the body's immune defense system. The use of "sicca-cell" preparations was provisionally forbidden in 1987 by the Federal Health Organization (Bundesgesundheitsamt; BGA). Prohibition of fresh-cell injections would have exceeded the authority of this office, although the same serious reservations also applied in the case of this treatment method. Several publications that have appeared since 1955 have reported serious complications of this therapy, some life-threatening and some even lethal. Two further cases are now added: (1) A woman aged 69 had been receiving treatment with cell injections for 9 years. Immediately after an injection of sicca cells she collapsed and was hospitalized; 7 days thereafter she developed an ascending paralysis with increasing inability to swallow or breathe. She died 25 days after the injection as a consequence of central and peripheral respiratory failure. Autopsy revealed the alterations typical for acute Landry-Guillain-Barré-Strohl syndrome. (2) A 76-year-old healthy woman had been receiving treatment with fresh-cell preparations for several years. After an injection of cell suspensions a painful local swelling was observed. The symptoms were interpreted as the consequence of an iatrogenic local hematoma, and repeated punctures were performed to obtain blood. The patient was transferred to a surgical department for further therapy. Two days after the injection she suddenly died with signs of acute cardiovascular failure. Autopsy revealed the signs of a fulminating clostridial infection and also the characteristic signs of Landry-Guillain-Barré syndrome with involvement of the autonomic nervous system. In both cases the development of an inflammatory process in the peripheral nervous system could be interpreted as an immune-mediated allergic disease, related to the repeated injection of heterologous antigenic material containing nervous tissues. This hypothesis would also explain the two other cases already published and would be consistent with the observed perivenous leukoencephalopathy of the central nervous system. The human disease pictures correspond to the well-established animal models of EAEM (experimental allergic encephalomyelitis) and EAN (experimental allergic neuritis). The pathogenesis is discussed; the major role of the central and peripheral nervous system is stressed, with special reference to the risk of acute autonomic failure. The need for specific autopsy techniques for the investigation of the entire nervous system, including spinal cord, roots, spinal ganglia and peripheral nerves with sympathetic chains, is raised.

Adult

Possible association of sudden infant death with partial complement C4 deficiency revealed by post-mortem DNA typing of HLA class II and III genes.

Based on evidence of an increased rate of respiratory infections in sudden infant death (SID) infants as well as the observation of familial occurrence, we analysed in a retrospective study class II and class II genes of the major histocompatibility complex in 40 cases of SID by Southern blot analysis of DNA obtained post mortem from tissue samples. In 24 cases, the parents were interviewed and confirmatory human lymphocyte antigen (HLA) and DNA typing was carried out. Using HLA-DR beta and -DQ beta probes, no evidence of an abnormal HLA-DR frequency distribution in SID infants was detected (P = 0.97). Using DNA probes for the tandemly arranged complement C4 and steroid 21-hydroxylase genes, an increased number of C4B gene deletions in SID cases was found. The increase in C4 gene deletions was significant (P = 0.0125) in infants with recurrent infections. These data indicate a possible role of partial C4 deficiency as a genetically predisposing risk factor in SID.

Complement C4

[Rare medicinal mercury poisoning].

After an accidental injury of the bowel during a hysterectomy, the patients peritoneal cavity was irrigated for disinfection with a solution containing a mercury-compound. The patient died 40 days after this "peritoneal lavage" with a 0.2% solution of mercury-II-oxycanide. The disinfection with the toxic compound during operation can be judged as a medical mistreatment leading to death of the patient. The mercury concentration in blood (0.1 mg Hg per 100 g blood), taken during autopsy, exceeded normal values severalfold. The cause of death was diagnosed as a "multiorgan-failure", caused by an "iatrogenic mercury poisoning". The results of toxicological analysis, histological examination and the findings of autopsy are presented.

Adult

[Stress and kinematic analysis of the head and neck in frontal collision. A comparison of voluntary probands and postmortem human test cadavers].

Investigations comparing dynamics and kinematics in volunteers and postmortem human subjects (PMHS) under the same collision conditions are rare, although such results are of elementary importance in order to estimate the suitability of PMHS as injury indicators in crash tests. Under this aspect, a report on 12 experimental frontal collisions has been made where PMHS were loaded and restrained by a 80 mm broad double shoulder lap-step belt. The impact velocity amounted 60 km/h, the mean vehicle decelerations were at 11 g and 15 g. In the Naval Biodynamics Laboratory in New Orleans, the comparing collective of 9 volunteers in the age range of 18 to 22 years has been investigated by a mean deceleration of 11 g at otherwise comparable conditions. Optical targets have been fixed at the 1st thoracic vertebra, the occiput and the top of the head in the PMHS, the collision phase has been documented by a laterally to the sled mounted high-speed camera with a frame rate of 1000 p/s. The accelerations have been measured tri-axial at the top of the head, at the clivus and the 1st thoracic vertebra. For the simulation of the muscle tonus of the volunteers, formaldehyde has been injected into the neck muscles. In the PMHS as well as in the volunteers no thoracic- or abdominal injuries occurred during the above mentioned loads. However, the spinal column of the PMHS remained uninjured only in 3 cases, in 7 cases hemorrhages in the intervertebral disc, lacerations of the ligamentum flavum or hemorrhages in the vertebral joints were observed.

Acceleration