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Biomedical subjects

G Fechner

Publications and source records attributed to G Fechner.

At least 19 recordsLinked to original sources

Sudden death due to giant cell coronary arteritis.

An 89-year-old woman was found dead lying in her bed. Autopsy demonstrated a pronounced thickening of all coronary arteries except for the first 2-4 cm. Death was due to a recent myocardial infarction. Microscopically, the coronary arteries showed a substantial concentric thickening of all three layers with 90% narrowing. There was a dense transmural inflammatory infiltration with lymphocytes, macrophages, and numerous multinucleated giant cells. The CD68 positive giant cells were mostly located at the media-intima border in the vicinity of fragmented fibers of the lamina elastica interna. The aorta and its major branches including the carotid arteries, however, were free of inflammation and thickening. The findings were characteristic for giant cell arteritis, the equivalent of temporal Horton arteritis, but isolated involvement of the coronary arteries is exceptional.

Aged, 80 and over↗

Randomised phase II trial of gemcitabine and paclitaxel second-line chemotherapy in patients with transitional cell carcinoma (AUO Trial AB 20/99).

The objectives are to evaluate and compare the response and toxicity of a 3-weekly and a 2-weekly regimen of gemcitabine (Gem) and paclitaxel (Pac) second-line treatment in patients with transitional cell carcinoma (TCC). Between June 2000 and July 2001, 30 patients with progressive disease (PD) during first-line chemotherapy (n = 11) or relapse after adjuvant cisplatin-based chemotherapy of a metastatic or locally advanced TCC (n = 18) have been randomised to receive either six cycles (schedule A) of 3-weekly Gem (1000 mg/qm, days 1 and 8) and Pac (175 mg/qm, day 1) or 2-weekly treatment until disease progression (schedule B) with Gem (1250 mg/qm, day 1) and Pac (120 mg/qm, day 2). Restaging was performed after every 6 weeks by clinical imaging. Of 30 patients, one patient in schedule A and two patients in schedule B were not evaluable for response due to serious adverse events (SAEs) during the first cycle. The overall objective response (OR) was 44% (12 of 27) with eight complete remissions (CRs) and four partial remissions. Median time to progression (TTP) was 11 (3-41) months in schedule A and 6 (1-15+) months in schedule B. Median survival was 13 (5-46) months in schedule A and 9 (0-16) months in schedule B. Schedule A showed a significantly higher rate of CRs (7 vs. 1, p < 0.05). With a median number of six (1-6) cycles (A) and nine (1-23) cycles (B), TTP and survival were not significantly different. In schedule B, one patient had WHO grade IV anaemia and leucopenia. WHO grade III toxicities were seen in schedule A/B as follows: anaemia 3 (23%)/2 (16%) patients, leucopenia 5 (38%)/2 (16%), thrombocytopenia 0/2 (16%) and alopecia 10 (76%)/4 (32%). The combination of Gem and Pac is an effective second-line regimen in patients with mainly poor prognosis due to PD after cisplatin-based chemotherapy. Except for three SAEs (uncertainly therapy related), both regimens were tolerated well. The 3-weekly schedule with a nonsplit Pac dose showed a significantly higher complete response rate in our small study population and, thus, might be superior to the 2-weekly schedule.

Adult↗

Reducing recurrence and costs in superficial bladder cancer: preclinical evaluation of osmotic cytolysis by distilled water vs. mitomycin.

Transurethral resection followed by instillation of chemotherapeutic agents such as mitomycin is considered as standard therapy in recurrent superficial bladder cancer. However, incidence of bladder cancer is increasing, and contrariwise resources to finance the health care systems are decreasing. Therefore, effective alternatives to expensive chemotherapeutics are necessary. Recurrence of bladder cancer after transurethral resection is mostly promoted by reimplantation of dissolved tumour cells which are therapeutical purpose of any intravesically instillated agent. Monolayer cultures of human RT112, RT4, T24 and TCC SUP bladder cancer cells were incubated and exposed to mitomycin or distilled water. Cell survival was determined by microculture tetrazolium assay. Distilled water led to significant cytolysis in all tumour cells. This effect was comparable to exposition to mitomycin. Distilled water and mitomycin have comparable in vitro effects in bladder cancer cells. These findings have to be substantiated by an animal model emphasising the aspect of larger tumour cell compounds or possible damage to healthy bladder tissue.

Antibiotics, Antineoplastic↗

Backstabbing--a report of an unusual case.

A case of a 25-year-old male with a deep knife stab injury in the back is reported. The stab wound penetrated the left thorax and the left lung was injured, a thoracotomy was performed and the patient survived. The injured man could not remember what had happened, his bag was missing and the incident was therefore considered to be due to a robbery. Further results of the police investigations and the forensic pathology inspection revealed an extremely unusual accident constellation.

Accidents↗

Fatal hepatic haemorrhage in a child-peliosis hepatis versus maltreatment.

A 2.5-year-old boy with known myotubular myopathy (Spiro-Shy-Gonatas syndrome) and gonadorelin intake 9 months ante-mortem was found dead in his bed at home. At autopsy a ruptured subcapsular haematoma of the liver with resulting haemoperitoneum (600 ml) was found. Both lobes of the liver showed numerous circular blood foci <1 mm-2 cm in diameter. Signs of mechanical trauma such as bruising of the abdominal wall were absent. Histologically, the blood cysts were commonly connected to the sinusoids but did not have an endothelial lining and the reticular fibres showed ruptures. These pathomorphological findings are characteristic for peliosis hepatis and the cause of death was therefore determined to be exsanguination due to hepatic haemorrhage from peliosis hepatis instead of from mechanical trauma. To our knowledge this is the youngest casualty from peliosis reported so far.

Blood↗

Preclinical evaluation of a radiosensitizing effect of gemcitabine in p53 mutant and p53 wild type bladder cancer cells.

OBJECTIVES: Despite clinical use, the radiosensitizing effect of gemcitabine (2'2'-difluorodeoxycytidine) in human transitional cell carcinoma (TCC) has not been shown to date. We investigated gemcitabine as a radiosensitizer for human TCC cells. METHODS: Monolayer cultures of RT112 (G1, p53 wild type), RT4 (G1-G2, p53 wild type), T24 (G3, p53, mutant type), and SUP (G4, p53 mutant type) cells were incubated in medium with gemcitabine. Electron beam radiation was applied alone, simultaneous, or 3, 6, 12, and 24 hours after gemcitabine. Jurkat leukemia cells were used as controls for radiation toxicity. Cell survival was determined 6, 12, 24, 48, and 72 hours after radiation by microculture tetrazolium assay. DNA damage was evaluated by flow cytometric assessment of poly(ADP-ribose) polymerase, and apoptosis was determined by terminal-deoxynucleotidyltransferase-mediated dUTP nick-end labeling and flow cytometric assessment after annexin-V and propidium iodide labeling. RESULTS: In all TCC cell lines, radiation alone caused only little and insignificant growth inhibitory effects at 10 Gy. Gemcitabine alone had a dose-dependent cytotoxic and apoptosis inducing effect on all TCC cell lines independent of p53 status. Assays combining radiation with gemcitabine in different dose and time schedules demonstrated no radiosensitizing effect in TCC cells. CONCLUSIONS: Gemcitabine is effective in TCC cell lines independent of p53 status. A radiosensitizing effect could not be demonstrated. Again, p53 status was not predictive of the radioresponse in the bladder cancer cell lines. Clinical studies with gemcitabine and radiotherapy might nevertheless yield different results but should be performed with utmost caution.

Animals↗

Death due to intravenous application of enteral feed.

A 6-month-old male infant was treated with intravenous infusions and enteral feed via a naso-gastric tube. Accidentally, enteral feed containing pureed carrots diluted with water was injected intravenously and the child died immediately. Carrot material could be found in the pulmonary blood vessels and in various organs of the systemic circulation.

Blood Vessels↗

Mycotic cerebral vasculitis in a paediatric cardiac transplant patient excludes misadventure.

We present the case of a 10-year-old girl with cardiomyopathy who received a heart transplant. Due to organ rejection, the dosage of immunosuppressive agents was increased postoperatively. The patient complained of intermittent headaches in the following days and developed a haemorrhagic necrosis of the left thalamus. A week later, an oral dose of cyclosporin A was accidentally given intravenously, and 2 weeks later a recurrent subarachnoid haemorrhage of unknown origin was diagnosed. The clinical course was then characterised by progressive deterioration resulting in coma, fluctuating brain stem symptoms and the development of a massive cerebral oedema with subsequent brain death. A coroner's autopsy was instigated to investigate a claim of medical misadventure. Neuropathological investigations found a focal infiltration of fungal hyphae in the left posterior cerebral artery resulting in necrosis of the vascular wall and thus explaining the source of the recurrent subarachnoid haemorrhage which eventually resulted in the girl's death. Medical misadventure due to the administration of cyclosporin was not directly responsible for the death of this patient. This case illustrates that it is of paramount importance to copiously sample and investigate the basal cerebral arteries in cases of subarachnoid haemorrhage of unknown origin, in particular in a medico-legal context.

Aspergillosis↗

Fatal intoxication due to excessive dichloromethane inhalation.

A 22-year-old white male was found dead at his working place in a car lacquering company. He had removed lacquer residues by using a solvent containing dicloromethane (DCM) without using a gas mask. Pathology revealed signs of asphyxiation with obvious petechial bleedings and expressed microthrombosis of the pulmonary arteries. Toxicological analysis showed excessive concentrations of DCM which are inhaled due to exposure of extreme air concentrations.

Administration, Inhalation↗

Fatal neglect of the elderly.

Maltreatment of the elderly is a common problem that affects more than 3% of the elderly. We report on two cases of fatal neglect. Risk factors of victims and caregivers were analysed in the context of the social history. In both cases, the victims had a dominant personality and the abusers (the sons) had been strictly controlled and formed by the parent. The victims showed typical risk factors such as living together with the abuser, isolation, dependence on care, income and money administration. Initially, the victims declined help from outside and self-neglect occurred. The unemployed perpetrators lived in social isolation and depended financially and mentally on the victims. In both cases no mental illness was present but there was a decrease of social competence. Legal medicine is predominantly involved in fatal cases in connection with external post-mortem examinations and autopsies. Also in the living, the medico-legal expert can assist in the identification of findings in elderly persons in cases of suspected abuse.

Aged↗

Proof of a gunshot wound and its delayed effects 54 years post injury.

In 1945 a 6-year-old girl received a tangential gunshot injury to the left posterior inferior skull. After hospitalisation because of septicemia she was unable to walk for several months. Since 1967 she had been repeatedly applying for compensation because of pseudoneurasthenia and residual ataxia and many medical examinations were performed including X-ray, CT and MRI. Although certain objective findings (e. g. cerebellar atrophy) could be verified, a causal connection between the gunshot injury and the clinical findings could not be established. Therefore previous investigators concluded on a vascular origin of the disease. During the present re-examination of the patient, the authors found patch-like scars at the left posterior inferior skull base and behind the left ear, a cord-like scar formation in the subcutaneous tissue, connecting both skin scars, a gutter-like defect in the left occipital base of the skull and an indention of the left mastoid process, both again in line between the skin scars and a large defect of the left cerebellar hemisphere. It could be concluded with certainty that the anatomical findings and the clicinal symptoms were the direct result of a gunshot injury. Previous investigations had failed because of deficient investigations and techniques. In addition to an anatomical reconstruction, three dimensional reconstructions from CT scans proved most helpful.

Ataxia↗

Effect of ethanol on dynamic visual acuity during vertical body oscillation in healthy volunteers.

Visual orientation is the most important sensory input during locomotion (e.g. walking, driving a car, riding a bicycle). We investigated dynamic visual acuity (DVA) during vertical body-oscillations (amplitude 5 cm; frequency 1.5 Hz) in 12 healthy subjects before and twice after ethanol consumption. During oscillation, vertical eye movements were recorded under two test conditions: with eyes closed (EC) and during DVA testing. A significant increase in vertical eye-amplitude after ethanol ingestion occurred only during EC tests, as a possible sign of vestibular hyperreaction. During vestibular stimulation alone (EC), ethanol did not affect the phase shift between stimulus and eye movements. However, when the subjects were given an additional visual stimulus (DVA), the post-alcohol phase shift rose significantly. Surprisingly, the post-alcohol phase shift values for the two test conditions showed no significant differences. After ethanol ingestion we found no changes in static visual acuity but a significant loss of DVA. Volunteers with a change of DVA threshold (DVAT) showed significantly (P = 0.004) higher post-alcoholic changes in the phase shift. In summary, low doses of ethanol disturbed the visually guided oculomotor response during fixation of an earth-fixed target while the observer was subject to linear vertical acceleration. This effect led to an increasing delay between the beginning of body and eye movements. The consequence was an increasing phase shift and thus a decrease in DVA during whole-body oscillation which was comparable to movements during human locomotion.

Acceleration↗

Effects of alcohol on body-sway patterns in human subjects.

The vestibulospinal aspects of vestibular function are commonly neglected in the evaluation of alcohol-induced intoxication. Thus, in the present study the effect of an acute intoxication with a low or moderate quantity of alcohol was examined with respect to the equilibrium in 30 healthy subjects. The blood alcohol concentration (BAC) was measured 30 min after the ingestion of the last alcohol, ranging between 0.22 and 1.59 per thousand. Stability of stance was quantified by static platform posturography in Romberg-test conditions with eyes open and eyes closed. Among other parameters, the average body sway path (SP) and area of body sway (SA) were assessed. Posturography revealed a significant increase in body sway. There was a positive correlation between SA (or SP) and BAC both with eyes open and eyes closed. Multiple group comparisons revealed that the large-alcohol-dose group (BAC > or = 1.0 per thousand) could be clearly differentiated from test cases with BAC lower than 0.8 per thousand. Sway area was the most sensitive parameter for detecting increased body sway after alcohol ingestion. The area increase, present not only with eyes closed but with eyes open, revealed an inadequate compensation of the ethanol-induced ataxia by visual stabilization. The Romberg's quotient, which denotes eyes closed relative to eyes open, remained constant. The increase in sway path with eyes closed showed an omnidirectional sway. A comparison of the sway pattern of subjects after acute ethanol ingestion with the data of patients with permanent cerebellar lesions suggested that the acute effect of alcohol resembles that of a lesion of the spinocerebellum. This finding contrasts with earlier studies, which postulated an acute effect of ethanol resembling that in patients with an atrophy of the anterior lobe of the cerebellum due to chronic alcohol abuse. In seven cases of the lower dose group (BAC < or = 0.8 per thousand), a reduction in body sway after alcohol ingestion was observed. This finding may be consistent with a dose-related biphasic action of alcohol, which - besides its well-known depressant effects with high doses - also shows stimulatory action with small doses.

Adult↗

Detection and analysis of tracers in experimental drowning.

In animal experiments, studies on the mechanisms involved in drowning were carried out using latex and gold tracers of defined size and concentration. The tracers were detectable by fluorescence microscopy (latex tracers) and by electron microscopy (gold tracers) in the lungs, kidneys and lymph nodes and were analysed further by X-ray microanalysis using a transmission scanning electron microscope. Tracers with small diameters were shown to penetrate intercellular gaps of the alveolar epithelium and the larger tracers were incorporated into the epithelial and endothelial cells by active pinocytotic mechanisms thus passing through the air-blood barrier. The detection and analysis of tracers in organs of the systemic circulation originating from the immersion fluid can assist in understanding the pathophysiology of drowning and in some selected cases, in making a more definitive diagnosis.

Animals↗

Ketoacidosis and lactic acidosis--frequent causes of death in chronic alcoholics?

In clinical medicine, severe keto- or lactic acidosis associated with vomiting, nausea, abdominal pain, tachycardia or pathological respiration, has been described in chronic alcoholics. This study reports on fatalities of chronic alcoholics where the cause of death could not be determined by thorough autopsy, histology and toxicology including determination of alcohol concentration. In a first series, acetone was determined in the blood of such chronic alcoholics (n = 24), diabetics with metabolic decompensation (n = 7), cases of hypothermia (n = 7) and controls (n = 218). Among the 24 chronic alcoholics where the cause of death was unknown, 9 cases showed very high levels of acetone (74-400 mg/l). These comprised 6 cases without additional findings and 3 cases where a second patho-mechanism such as intoxication possibly contributed to the cause of death. In a second series, the sum values according to Traub (lactate/glucose) were determined in cerebrospinal liquor of chronic alcoholics with undetermined cause of death (n = 45), diabetics (n = 6) and controls (n = 39). Among the 45 alcoholics, 17 cases showed very high sum values (294-594 mg/dl) including 8 cases where non-lethal intoxications may have contributed to the final outcome. Other causes of a ketoacidosis or lactic acidosis (e.g. diabetes) were excluded in both groups of alcoholics. Consequently, ketoacidosis and lactic acidosis can be the cause of death of chronic alcoholics in a considerable number of cases where no pathomorphological or toxicological changes are present. A scheme for medical and laboratory examination is described.

Acetone↗

DNA-typing of cellular material on current conductors.

The examination of deaths due to electricity may require a comparison between current marks on the body and the electrodes suspected to have caused them. Normally the identification of the responsible electrode is carried out by analysing metal traces on the current marks. We however examined the conductor for traces of biological material after experimentally produced current marks. The surfaces of the conductors were investigated using a low-power macroscope and burnt tissue could always be recognised. Subsequently, all electrodes were carefully swabbed, extracted with chelex and typed for short tandem repeat polymorphisms using PCR. This procedure was successful in all cases. Therefore, DNA analysis can be a powerful tool to supplement conventional scene reconstruction in cases of deaths due to electricity.

Autopsy↗

The distinction between lacerations and cuts in ligaments and tendons.

In contrast to skin wounds the characteristic forensic features of lesions of ligaments and tendons have rarely been investigated. However, in a suspected homicide the question became crucial whether an isolated discontinuity of the posterior atlanto-occipital membrane was caused by a rupture mechanism or by a cut. In order to reevaluate the associated criteria experimental lesions were made in ligaments and tendons and examined histologically. From these experiments the following criteria could be established: Lacerations exhibit complete destruction of the tissue texture with microruptures and splitting of fibres in the adjacent region. Such would edges have an irregular structure and fibres near the rupture site exhibit variable thicknesses due to traction. Incisions exhibit smooth wound edges with no disturbance of the tissue texture. The thickness of fibres near the rupture site is regular. These results were obtained by light microscopical examination and confirmed using electron microscopy. Under controlled experimental conditions the forces necessary to rupture tendons with a diameter of 1 mm varied between 50-70 Newton (N). In the suspected homicide, the lesion of the posterior atlanto-occipital membrane was examined visually and histologically and was compared with the experimentally established criteria. Based on these criteria the lesion could be identified as an incision which had probably been caused accidentally while severing the medulla during the first autopsy and was therefore not connected with the cause of death.

Adult↗

[Pathophysiology of post-traumatic anosmia].

BACKGROUND: Head injury is one of the most common causes of olfactory disturbances. The incidence of posttraumatic anosmia depending from the severity of the injury lies between 5% and over 80%. METHODS: Clinical assessments were performed in 26 cases with posttraumatic anosmia using subjective olfactometric tests. Additionally, morphological studies were performed in 26 other patients, who died between 36 hours and six weeks after head injuries. RESULTS: Frontal basal injuries as well as minor occipital blows are capable of causing complete olfactory loss. About one-third of all patients were not aware of their chemosensory deficits, especially when associated neurological deficits occurred. Moreover, the studies show that: 1: The vulnerability of the fila olfactoria varies extremely and depends on unknown, highly individual parameters. 2: Trauma can induce local hemorrhage within the olfactory tracts and bulbs without any other intracranial lesions. 3: An intracerebral contusion is often misunderstood as the direct substrate of a posttraumatic anosmia. However, in a number of cases it is merely the sign of a strong injuring force, potentially capable of injuring the fila or the olfactory bulbus. CONCLUSIONS: The findings indicate that the pathophysiology and biomechanics of posttraumatic anosmia should be the subject of critical discussion.

Accidents, Traffic↗