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Time course of nigrostriatal degeneration in parkinson's disease. A detailed study of influential factors in human brain amine analysis.

It could be shown that the post mortem analysis of biogenic amines, precursors and metabolites in the human brain are influenced by various parameters. 1. The patient's medical history; long term observations of the course of the disease; age; sex. 2. Terminal illness; duration of terminal illness. 3. Previous treatment with drugs; last drugs. 4. Time interval between last drug treatment and death; time of day and date of last drug consumption. 5. Rapidity of death; time of death; duration of coma. 6. Changes occurring in tissues before death; patients' constitution during terminal illness. 7. Changes in concentration of the biogenic amines, precursors, and metabolites depending on the patient's age. 8. Time between death and necropsy. 9 Dissection of specimen. 10. Period of storage; temperature of storage. 11. Chronbiological rhythm of substances. 12. Methods of assayL 13. Homogeneity of all mentioned parameters in the control group and patient's group. For the first time it could be demonstrated that the time course of nigrostriatal degeneration, independent of the age of the parkinsonian at the beginning of the illness, is linear for the last stage and the denervation progressively increases as the duration of illness progresses.

Age Factors↗

Moral considerations in body donation for scientific research: a unique look at the University of Tennessee's anthropological research facility.

This paper discusses keys to the moral procurement, treatment and disposition of remains used for scientific research, specifically those donated to the University of Tennessee's Anthropological Research Facility (ARF). The ARF is an outdoor laboratory dedicated to better understanding the fate of human remains in forensic contexts, and focuses its research on decomposition, time since death estimates, body location and recovery techniques, and skeletal analysis. Historically, many donations were unclaimed bodies received from medical examiners (although it will be shown that this trend is changing), and it has been argued that the use of the unclaimed bodies for medical or scientific purposes is a violation of autonomy since no consent was given by the individual. It is argued here, however, that the domain of autonomous choice extends to one's own corpse only insofar as expressed wishes are made known prior to one's death, and that in the absence of expressed intent toward final disposition, it is acceptable for institutions to receive donations from medical examiners or family members. This paper also discusses other philosophical issues related to donation, consent and autonomy, and the forensic benefits of research conducted at the Anthropological Research Facility.

Cadaver↗

Pathological changes in the organ of Corti in presbyacusis as revealed by microslicing and staining.

A new technique of examining the organ of Corti in the perfused human cochlea is described. The fixed cochlea is microsliced and surface preparations are prepared and then stained for light microscopy. A method of assessing the distance/length ratio of samples is also described. Counts of inner and outer hair cells in such stained surface preparations were performed on elderly subjects and compared with those of infants. A marked loss of outer and a mild loss of inner hair cells was present in the elderly subjects. Complete atrophy of variable lengths of the terminal basal coil cells was also found in all elderly cochleas. Giant stereociliary degeneration takes place in hair cells (except basal coil outer hair cells) before they disappear.

Aged↗

Proteolytic and physicochemical mechanisms involved in meat texture development.

Development in meat texture is a complex process originating very likely from a softening of the structural elements, especially myofibrils. This process probably involves two sets of mechanisms: 1) an enzymatic mechanism involving at least two of the three proteolytic systems so far identified and present in this tissue, namely lysosomal (cathepsins) and calcium dependent (calpains) proteinases; 2) a physicochemical mechanism based on the important post mortem rise in muscle osmotic pressure which could be twice as high as in live animals. Despite the large progress in muscle enzymology, the nature of the proteinases responsible for the post mortem proteolysis associated with the development in meat texture is still not clearly established. In the present review, data obtained from two different approaches attempting to answer this question were analysed. The first one was based on the identification of a set of structural and biochemical changes associated with meat texture development and to examine which proteolytic system or proteinase would be able to reproduce them when incubated with either myofibrils or muscle fibres as substrate. The second tentatively relates the rate and the extent of the changes in meat texture to the proteolytic equipment of the tissue. The first approach led to the conclusion that changes in muscle proteins and structure can be only explained by considering a synergistic action of both lysosomal and calcium-dependent proteinases. From the second, it was concluded that the process of meat texture development did not depend on the proteinase levels but was related to their initial potential efficiency assessed by measurement of the enzyme/inhibitor ratio. With respect to the physicochemical mechanisms, the post mortem rise in muscle osmotic pressure was shown to be responsible for some biochemical changes occurring in myofibrils. This was further substantiated by the fact that the greatest osmotic pressure values were observed in muscles exhibiting highest tenderising rate. On the other hand we provide evidence suggesting that the substrate, namely myofibrils, might constitute an important limiting step of the efficiency of both types of mechanism. Taken together, the findings presented emphasize that improvement of our knowledge in this field will greatly depend on the development of basic research on these different topics notably: 1) the mechanisms by which proteinases activities are regulated in living and post mortem muscles; and 2) the myofibrillar structure, especially in slow-twitch or type I muscles.

Adenosine Triphosphatases↗

Novel methods for determining the vital reaction in injured skin.

The authors devised two new methods for determining the vital reaction of injured skin and tentatively termed them Method I and Method II. Method I is based on the determination of "fibrin-forming ability" of slices of injured skin in the presence of added fibrinogen. Method II is based on the measurement of the albumin content in the injured skin by rocket-immunoelectrophoresis. These methods have the following characteristics: Both are able to distinguish ante-mortem from post-mortem wounds, even in fresh vital wounds. The fibrin-forming ability in vital wounds undergoes a post-mortem change, and this can be used to distinguish ante-from post-mortem wounds for 2 days after death. On the other hand, the albumin content of wounds is virtually unchanged post-mortem until one week after death. Method II is therefore applicable even to slightly decomposed materials one week after death. It is not recommended that this method be used for the wound in the post-mortem hypostatic area. Regarding the technique, both methods are relatively easy. Both methods are able to estimate the wound age until about 2 days after injury (during wound healing). A more reliable estimate of wound age is possible by using Method I together with Method II.

Animals↗

Decomposition of buried corpses, with special reference to the formation of adipocere.

The unrestrained decomposition of a corpse involves the consecutive processes of autolysis, putrefaction and decay. Ideally, decomposition is completed within the regular resting time (15-25 years) and leads to the entire skeletalisation of the corpse. Adipocere, a greyish fatty substance formed during decomposition, is regarded as a spontaneous inhibition of post-mortem changes; it makes the corpse almost entirely resistant to decomposition and makes it impossible to use the same graves again. This creates problems for local governments with regard to the generally growing demand for burial ground. Apart from corpse-specific characteristics (e.g. sex, age, physique, cause of death), method of burial (e.g. material of the coffin, depth of grave, individual or mass grave, clothing) and time of burial, the conditions of the resting place (geology, topography, soil properties and frequency of use, air, water, and heat budget), in particular, have a special impact on adipocere formation. This study summarises the present knowledge on this phenomenon, combining results gained both in forensic medicine and in geosciences.

Cadaver↗

Comparative morphology of the airways in asthma and chronic obstructive pulmonary disease.

Asthma and chronic obstructive pulmonary disease (COPD) are complex conditions with imprecise definitions that make definitive morphological comparisons difficult. Asthma may be divided into extrinsic (allergic), intrinsic (late onset), and occupational forms. The airways in fatal asthma are occluded by markedly tenacious plugs of exudate and mucus; there is fragility of airway surface epithelium, thickening of the reticular basement membrane, and bronchial vessel dilatation, congestion, and edema. There is enlargement of bronchial smooth muscle and also of submucosal gland mass, particularly in medium-sized bronchi. There is increased inflammatory infiltrate comprising activated lymphocytes and eosinophils with release of granular content in the latter; the allergic inflammation is associated with gene expression for interleukins IL-4 and IL-5 (ie, TH2 phenotype) and also GMCSF and TNF alpha. Many of these changes are already present in mild forms of asthma. In comparison, three conditions contribute to COPD: (1) In chronic bronchitis there is inflammation associated with mucous hypersecretion, enlargement of tracheo-bronchial submucosal glands, and a disproportionate increase of acidic mucus. The reticular basement membrane is not consistently thickened. (2) In small (peripheral) airways disease there is a macrophage bronchiolitis, mucous metaplasia and hyperplasia, increased intraluminal mucus, increased wall muscle, fibrosis, and airway stenoses. Respiratory bronchiolitis and loss of alveolar wall attachments are important lesions. (3) Emphysema involves elastolytic destruction of the alveolar wall; its overall severity, rather than type, appears to be an important determinant of chronic irreversible deterioration of airflow in COPD.

Asthma↗

Dopamine receptors in the Parkinsonian brain.

Striatal dopamine receptors were studied in 44 patients with Parkinson disease by the radioligand-binding technique using 3H-spiroperidol. The specific binding of 3H-spiroperidol was either significantly increased or reduced in the caudate nucleus and putamen of parkinsonian patients without levodopa therapy. Scatchard analysis showed that there were corresponding changes in the receptor number, but no significant changes in the mean dissociation constant. The increased binding of 3H-spiroperidol in the basal ganglia was also found in parkinsonian patients suffering from psychotic episodes and treated with neuroleptic drugs. Normal and low binding of 3H-spiroperidol was found in patients treated with levodopa. Clinically, the patients with low binding were more disabled and had lost the beneficial response to levodopa. Thus in Parkinson disease in some patients a denervation supersensitivity seemed to develop and in some others a loss of postsynaptic dopamine receptor sites in the neostriatum. The latter alteration may contribute to the decreased response of parkinsonian patients to chronic levodopa therapy.

Aged↗

2. Haemorrhoids leading to post-mortem artefact: a case report.

Any change produced, or feature introduced, in a body after death which is accidentally or physiologically unrelated to the natural state of the body is termed as an artefact. Since artefacts may lead to misinterpretation of post-mortem findings, it is important to rule them out. Artefacts may be produced for a variety of reasons. We present a case report where a young male in his late twenties committed suicide by hanging. He was suffering from haemorrhoids. Because of his posture, there was post-mortem bleeding, which was interpreted by the police as bleeding due to the self-cutting of his veins. Hence, we felt the need to report this case.

Adult↗

Bodies found in the waterways of New York City.

We reviewed the case records for all decedents recovered from the waterways of New York City over a three year period (1997-2000). The epidemiological profile, circumstances, toxicology findings, putrefactive changes, date of recovery, length of immersion, and injuries were examined. There were 123 deaths: 52 suicides, 50 undetermined, 16 accidents, and five homicides. The causes of death included: 97 drownings, 13 undetermined, and 13 other. Of all the floating decedents, 27% were without putrefactive change. All found after two or more weeks of immersion were recovered from November to May. The detection of ethanol and illicit drugs was 53% in the accident, 41% in the suicide, and 33% in the undetermined groups. Detection of ethanol and/or drugs of abuse is not a reliable criterion to distinguish suicide from accident. The identification of the deceased is pivotal for determining the manner of these deaths. Therefore, a great reliance is placed upon the medical investigator and the police (including the missing persons bureau) to determine the circumstances and identification of the decedent.

Adolescent↗

[Changes in the UV spectrum of the vitreous body in relation to the time of death].

The UV spectrum of 40 samples of vitreous body was determined in different time periods after death. The vitreous body was diluted in the ratio 1:200 and 1:400 by means of redistilled water. It was found that the ratio of absorbance corresponding to the peaks of the curve is dependent on the time period after death. The regression analysis determined an exponential relation, making possible to estimate the time period after death in the dilution of the vitreous body in the ratio 1:200. For this kind of determination cases of deceased persons with damaged brain or cases with too high an absorbance did not prove suitable. In the dilution 1:400 the variance was too high and did not provide data that would be suitable for determining an estimate of the time elapsed from death.

Forensic Medicine↗

A histological study of post mortem changes in the skeletal muscle of the fowl (Gallus domesticus). I. The muscle fibres.

The changes in the histology of skeletal muscle post mortem have been studied with the light and electron microscopes in the pectoralis thoracica and iliotibialis muscles of the fowl (Gallus domesticus). The carcasses were stored at 40 degrees C and samples removed at various times post mortem. Kinking, contractures, transverse splitting and disintegration were seen in muscle fibres from post mortem muscle. The variation in time and frequency of occurrence of these was wide but no consistent difference between the pectoralis and iliotibialis muscles was found. An attempt was made to integrate the results from the light and electron microscopes to gain insight into the nature of the modifications occurring in the histology of post mortem muscle fibres.

Animals↗

Rectal temperature time of death nomogram: sudden change of ambient temperature.

Cooling experiments on dummies known as body-like cooling were performed with sudden decrease and increase of ambient temperature in the order of 15 degrees C. In the case of a sudden decrease of ambient temperature, a second 'temperature plateau' occurs which is shorter than the known plateau at the beginning of body cooling. The cooling curves can be described mathematically by a three-step procedure based on the two-exponential term of the 'nomogram method'. The second plateau at the beginning of the second cooling phase in sudden decreased ambient temperature requires a lower value of the constant A (1.15) compared with the known value (1.25) at the beginning of body cooling. In the case of a sudden increase of ambient temperature in the order of 15 degrees C no procedure could be found to model the cooling curves mathematically.

Air↗

Further studies on the therapy of organophosphorous anti-cholinesterase intoxication with veratrinic compounds; the role of calcium.

Experiments were carried out to investigate the role of calcium in the therapy of soman intoxication with 9-anthroic acid (ANCA), a compound with veratrine-like pharmacological properties. The effects of ANCA on the respiratory paralysis and on the calcium content of the blood and that of the hindleg muscles were determined in anaesthetized, atropinized rats injected with 4 times LD50 soman. The respiratory paralysis which in control animals occurs within a few min after the injection of soman can be delayed about 2.5 hr by treatment with ANCA. It was found that ANCA causes a small decrease of the blood calcium content, an effect which is potentiated by soman. A comparison was made between the calcium accumulation in the indirectly stimulated gastrocnemius-soleus muscles in these animals with that in the non-stimulated muscles on the other side. Whereas the injection of soman or ANCA alone caused no change, the combination of the two drugs induced a two-fold increase in the accumulation of calcium in the stimulated muscles. The non-stimulated muscles remained unaffected. The accumulation of calcium in the stimulated muscles induced by soman and ANCA could be partly antagonized by lowering the free calcium concentration of the blood by EDTA. Moreover, treatment with EDTA improved the therapeutic effects of ANCA. It is concluded that the therapy of soman poisoning with ANCA falls short in completely preventing respiratory failure since ANCA causes an accumulation of calcium in the stimulated muscles of soman-poisoned animals.

Animals↗

Brain ferritin iron may influence age- and gender-related risks of neurodegeneration.

BACKGROUND: Brain iron promotes oxidative damage and protein oligomerization that result in highly prevalent age-related proteinopathies such as Alzheimer's disease (AD), Parkinson's disease (PD), and Dementia with Lewy Bodies (DLB). Men are more likely to develop such diseases at earlier ages than women but brain iron levels increase with age in both genders. We hypothesized that brain iron may influence both the age- and gender-related risks of developing these diseases. METHODS: The amount of iron in ferritin molecules (ferritin iron) was measured in vivo with MRI by utilizing the field dependent relaxation rate increase (FDRI) method. Ferritin iron was measured in four subcortical nuclei [caudate (C), putamen (P), globus pallidus (G), thalamus (T)], three white matter regions [frontal lobe (Fwm), genu and splenium of the corpus callosum (Gwm, Swm)] and hippocampus (Hipp) in 165 healthy adults aged 19-82. RESULTS: There was a high correlation (r>0.99) between published post-mortem brain iron levels and FDRI. There were significant age-related changes in ferritin iron (increases in Hipp, C, P, G, and decreases in Fwm). Women had significantly lower ferritin iron than men in five regions (C, T, Fwm, Gwm, Swm). CONCLUSIONS: This is the first demonstration of gender differences in brain ferritin iron levels. It is possible that brain iron accumulation is a risk factor that can be modified. MRI provides the opportunity to assess brain iron levels in vivo and may be useful in targeting individuals or groups for preventive therapeutic interventions.

Adult↗

Foreign compound metabolism studies with human liver obtained as surgical waste. Relation to donor characteristics and effects of tissue storage.

An investigation has been conducted on the foreign compound-metabolizing activity of human liver collected fresh from surgery or at autopsy from cadavers 3 to 18 hr old, and the effects of low temperature storage on the foreign compound-metabolizing activity of fresh human liver. The enzyme activities studied were microsomal cytochrome P-450 content, biphenyl 4-hydroxylation, benzo-(a)pyrene metabolism, halothane reduction, and 4-hydroxybiphenyl UDP-glucuronosyl transferase, as well as cytosolic thiopurine methyltransferase, thermostable (TS) phenolsulfotransferase, thermolabile (TL) phenolsulfotransferase, and 5-fluorouracil dehydrogenase. Cadaver liver was a poor source of material for metabolism studies with the majority of the enzymes investigated. There was an 84% decrease in the yield of microsomal protein, a 64% decrease in cytochrome P-450 content per mg of microsomal protein, and a 36% decrease in the biphenyl 4-hydroxylase specific activity in human cadaver liver that was a few hours old. UDP-glucuronosyl transferase showed a 70% decrease, TS phenolsulfotransferase a 84% decrease, TL phenolsulfotransferase a 97% decrease, and thiopurine methyltransferase no significant change in specific activity. The loss of activity for many of these enzymes could be simulated by keeping fresh human liver at the temperature of the body after death. Surgical waste provided a good source of fresh, histologically normal, human liver for metabolism studies. Microsomal cytochrome P-450 content showed a significant increase with the age of the liver donor. Metabolism of benzo(a)pyrene to 3-hydroxybenzo(a)pyrene and benzo(a)pyrene-7,8- and -9,10-diols showed up to 136% higher rates in fresh liver microsomes from female donors.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Changes of pituitary hormones in brain death.

In six patients with clinical and electroencephalographic signs of brain death, pituitary hormones such as prolactin, human growth hormone (GH), luteinizing hormone (LH), and thyrotrophin (TSH) were measured in blood close to the demonstration of intracranial circulatory arrest by angiography. In addition, pituitary hormone releasing tests and an insulin test were carried out in two patients. The results showed that no patient had a general decrease in hormone levels, according to their biological half life times, which suggests there still was some function in the hypothalamus and pituitary. This was supported by the results of the stimulation tests. It is concluded that in brain death some basal parts of the brain may still be perfused despite the fact that angiography indicates circulatory arrest in these areas.

Adolescent↗

Estimating time of death from measurement of the electrical excitability of skeletal muscle.

Post-mortem contraction was measured using sensitive force transducers inserted into human muscle. The muscle was stimulated using rectangular impulses of 1 sec duration and known current intensity. After some time, a noticeable change of the muscular contraction occurred, from a two-peak to a one-peak shape. The maximum force of the muscular contraction using a stable current intensity decreased with time since death, but relaxation time increased. The decrease of the maximum force and the increase of the relaxation time were used as criteria for extrapolating the time since death in a random sample of 50 bodies. The calculated 95% limits of confidence were 2.85 h (decrease of the maximum force) and 2.7 h (increase of relaxation time) up to 13 hours post mortem. The calculated 95% limits of confidence were checked on an independent sample of 21 bodies and proved to be reliable.

Adolescent↗