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Clinical correlates of postmortem brain changes in schizophrenia: decreased brain weight and length correlate with indices of early impairment.

From a postmortem study of the brains of 56 patients with schizophrenia and 56 controls, 38 cases whose clinical state had been objectively documented in life were examined to determine whether relations existed between features of the illness and postmortem findings. Decreased brain weight was significantly related (p < 0.05) to poor premorbid global function and to poor academic record, and decreased brain length was related to poorer premorbid global function (p < 0.05) and more severe negative symptoms. These relations are consistent with the view that morphological changes in the brain occur early in the course of the disease--that is, they are in some sense "developmental." An excess of "focal damage" in the patient group relative to controls was unrelated to the presence of morphological change or to features of illness, but was more common in female schizophrenic patients and was also correlated with evidence of cerebrovascular disease. This may possibly be due to a discrepancy between the groups in mode and cause of death.

Brain↗

[Effect of environmental temperature on the course of spontaneous postmortem pupillary changes (studies of the rabbit eye)].

The diameter of the pupils was measured in the bodies of rabbits under different ambient temperatures (2-4 degrees C, 10-12 degrees C, 18-20 degrees C, 28-30 degrees C). It was found that the pupils changed in three phases: Initial miosis, which set in within minutes after death, was followed by a mydriatic phase, which lasted several hours and was approximately synchronous with the post-mortem rigidity of the skeletal muscles. In the third phase the pupils slowly contracted in the course of several days. The higher the ambient temperature, the more marked was the dilatation of the pupils in the second phase. In contrast to this the reaction of the pupils was characterized by less pronounced changes in size and a longer duration of secondary mydriasis, when temperatures were low.

Animals↗

Identification of high molecular weight proteins in squid muscle by Western blotting analysis and postmortem rheological changes.

The high molecular weight protein connectin (also called titin) in Japanese common squid (Todarodes pacificus) mantle muscle was identified by western blotting analysis with 3B9, the mouse anti-chicken skeletal muscle connectin monoclonal antibody. Similarly to vertebrate samples, there exists connectin in invertebrate squid mantle muscle, and the amino acid sequences are assumed to resemble those present in the A band of vertebrate connectin, judging by the specificity of 3B9. Moreover, the connectin in squid muscle migrated in this study as a closely spaced doublet of alpha and beta (titins 1 and 2). Between 5 and 7 h post-mortem, the SDS PAGE patterns of the squid sample indicated a change of the doublet bands into a single beta-connectin band. Simultaneously, the rheological properties of the squid muscle changed substantially. This degradation of alpha-connectin into beta-connectin in the muscle can explain the critical change that occurs during the post-mortem tenderization of squid muscle.

Animals↗

Lack of predictable site-dependent differences and time-dependent changes in postmortem concentrations of cocaine, benzoylecgonine, and cocaethylene in humans.

This study evaluated the stability of cocaine, benzoylecgonine, and cocaethylene in postmortem fluids in cases of cocaine-related death. Femoral and ventricular blood and cisternal cerebrospinal fluid were collected soon after death and again at the time of autopsy. In addition, iliac blood was collected at autopsy. There were no consistent patterns of site-specific differences for any of the analytes, and the central compartment showed both higher and lower concentrations than the peripheral. There was no consistent pattern of direction or magnitude of change in the concentrations with respect to time for any of the analytes. This is consistent with anecdotal reports from other workers and is believed to be a result of competing processes of tissue release and chemical and enzymatic degradation of the analytes. Postmortem cocaine and metabolite concentrations in blood are not necessarily reflective of the perimortem concentrations and should not be the primary consideration in determining the cause of death in suspected cocaine-related deaths.

Adult↗

Pathology and pathophysiology of Meniere's disease.

Histopathologic study of the human temporal bone entails microscopic examination and analysis of a series of histologic sections. This is currently the most effective method for observing the pathologic conditions of MD by examining the entire inner ear. Complete temporal bone histopathology cannot be replaced by either clinical pathologic study of small biopsy specimens obtained during surgery, or experimental animal studies that can create endolymphatic hydrops but not create MD. We believe that the histopathologic findings together with clinical information on MD is valuable in enhancing our understanding of the pathophysiology of the inner ear in MD. For example, a hypoplastic VA and ES in MD seem to indicate that there may be congenital predisposing factors in the development of MD. The exact pathologic findings characteristic of MD remains unclear, however. Many of the temporal bone specimens were obtained years after patients were diagnosed with MD and those specimens were involved with moderate postmortem changes. For these reasons, further collection of temporal bone specimens with fewer postmortem changes, obtained within a shorter premortem time period between occurrence of the disease and the time of the patients' death, and from patients with a well-characterized clinical history of MD, is imperative. Contemporary temporal bone studies now include in situ hybridization histochemistry or polymerase chain reaction (PCR) analysis for protein, enzymes, or viral antigens that can be directed at specimens from patients with MD [54,55]. It is hoped that in the near future such advanced research studies with human temporal bone histology sections will support and enhance the significant contribution of temporal bone histopathology to clinical otology.

Autopsy↗

Anitschkow nuclear changes in postmortem pericardial scrapings.

OBJECTIVE: To document the presence of Anitschkow nuclear changes (ANC) in pericardial mesothelium at autopsy after the incidental finding of ANC in pericardial scrapings from a fatal case of overwhelming sepsis. STUDY DESIGN: Fourteen, nonconsecutive autopsy cases were studied. Using the edge of a scalpel, the visceral pericardium from the left ventricle was scraped, and the sample was smeared onto glass slides, fixed in 95% ethanol, Papanicolaou stained and evaluated for the presence of ANC. Histologic correlation was also performed. RESULTS: ANC were observed in pericardial mesothelial cells in 6 of 14 cases. Sepsis was the cause of death in three. Fatal cardiac arrhythmia, T-cell lymphoma and fulminant hepatic necrosis were found in the remaining cases. While readily seen in cytologic preparations, ANC were found focally in only one case examined histologically. CONCLUSION: Postmortem cytologic evaluation provides information relevant to the autopsy. In this study, ANC were very clearly seen in six pericardial scrapings. Clinical correlation supports the current theory that ANC represent a nonspecific reactive cell change.

Adult↗

Estimation of postmortem metabolic changes in porcine brain tissue using 1H-MR spectroscopy--preliminary results.

To investigate the potential for estimating the time since death by monitoring the evolution of different metabolites in brain tissue by (1)H-MRS, an animal model using pig heads was established. The maximum examination interval was 3 weeks. Within this time interval spectra revealed different compositions of metabolites, including metabolites observed in the normal brain and as products of bacterial decomposition processes (N-acetyl-aspartate 0-130 h, creatine 0-170 h, bound trimethylammonium, e. g. choline compounds, during the whole time course with fluctuating intensities, lactate 0-200 h, alanine and acetate during the whole time course, succinate and free trimethylammonium after approx. 100 h postmortem). The proposed approach may offer a new method to estimate later postmortem intervals although these observations have to be confirmed by further studies.

Acetates↗

[The dynamics of postmortem cellular changes. Ultrastructural-histochemical research].

Lactate dehydrogenase (LDG), glucose-6-phosphate dehydrogenase (G-6-PDG), isocitrate dehydrogenase (ICDG) as well as acid phosphatase (AcPase) activities were assessed in the rat tracheal ciliated epithelial cells using cytophotometry, combined with ultrastructural AcPase demonstration within 1 to 5 hours after animal death. A moderate gradual reduction of LDG, G-6-PDG and AcPase, but not ICDG activities has been detected in the groups of initially unaffected and hypertensive rats. The activities of all dehydrogenases progressively decreased compared to the stable AcPase values in rats which died from acute renal failure. AcPase reaction products were found to be released from the Golgi apparatus and lysosomes into the adjacent cytoplasm and across the plasma membrane. Occasionally AcPase activity emerged in the cis- and intermediate lamellae of the Golgi apparatus. The perturbations in the membrane permeability evidenced by AcPase leakage can be considered as the most likely mechanism for the observed postmortem reduction of some enzymatic activities tested.

Acid Phosphatase↗

Postmortem functional changes in coronary and cerebral arteries from humans and monkeys.

Contractile responses to 30 mmol . litre-1 K+ of helical strips of coronary arteries from human cadavers did not change within 5 h after death; however, they were suppressed 8 h after death. In coronary arteries from monkey cadavers, the K+-induced contractions did not significantly differ within the first 5 h, but were suppressed 12 h after death. On the other hand, K+-induced contractions were retained without deterioration in cerebral artery strips from human cadavers 20 to 24 h after death and those from monkey cadavers 8 to 16 h. Acetylcholine caused contractions of human coronary arteries, but caused only a relaxation of monkey coronaries which was abolished by rubbing off the endothelium. These responses were attenuated by no more than K+-induced contractions up to 12 h after death. Maximum contractions induced by noradrenaline, histamine and serotonin remained the same in human coronary arteries for 3 to 5 h after death. Similar magnitudes of contraction were elicited by noradrenaline in human cerebral arteries up to 20 h after death. It appears that the reactivity of human coronary arteries to K+ and other vasoconstrictor agents used is normally retained for at least 6 h after death and that of human cerebral arteries up to 24 h.

Adolescent↗

[A study on the relationship between the degradation of protein and the postmortem interval].

OBJECTIVE: To observe the degradation of actin and tubulin in the liver tissue of rats after death and to find an objective indicator of the postmortem interval (PMI). METHODS: Female rats were killed under anesthesia by ether and incubated at 21 degrees C in a temperature controlled system to simulate postmortem changes for 18 days postmortem. Protein in the hepatic tissue was extracted, actin and tubulin were then examined by western blot. Thereafter, the semi-quantitative analysis of the image of western blot was performed. RESULTS: Actin in the liver tissue of rats could be detected at 8 days postmortem, but could not be examined after 10 days postmortem. beta-tubulin rather than alpha-tubulin could be examined after 2 days postmortem, and beta-tubulin could not be examined at 4 days postmortem. CONCLUSION: There is some difference in the degradation between actin and tubulin, their different preservation period postmortem may be used as a parameter for PMI estimation.

Actins↗

[Detection on morphine concentration changes of postmortem cardiac blood in rats by HPLC].

This study used HPLC to detect the concentration of morphine in cardiac blood of rats treated with intramuscular injection of therapeutic and toxic dose morphine. The results showed, in the group with therapeutic dose morphine, the cardiac blood concentration of morphine increased significantly within 96 h after death (P < 0.01), these increase of the cardiac blood morphine correlated well with time. In the group with toxic dose morphine, the cardiac blood concentration of morphine did not change obviously within 12 h after death, but increased gradually 24 h, 48 h, 96 h after death (P < 0.01), however, the morphine changes intensity is not more significant than the therapeutic dose. This study proved that the dose of morphine injected antemortem affects directly the postmortem cardiac blood morphine levels. It is analysed for the possible mechanism of the change.

Animals↗

Post-mortem changes in cytochemical localization and enzymological measurement of marker enzymes of the mitochondria, SDH and Mg-ATPase, of porcine muscle stored at 4 degrees C, -18 degrees C, or -80 degrees C.

As a series of studies on postmortem changes in the fine structure of porcine muscle, activity of two mitochondrial marker enzymes, succinate dehydrogenase (SDH) and magnesium dependent adenosine triphosphatase (Mg-ATPase), was measured and localized in cardiac, red and white muscles stored at 4 degrees C, -18 degrees C or -80 degrees C. The postmortem loss of SDH activity was most remarkable in cardiac muscle. The variation of SDH activity was proportional to the amount of absolute activity. The postmortem change of Mg-ATPase was more variable than SFH, though the activity was well preserved up to 15 weeks in all three types of porcine muscle stored at -80 degrees C. The loss of Mg-ATPase was most remarkable in red muscle stored at -18 degrees C or -80 degrees C. Cytochemical localization of SDH was between the outer and the inner mitochondrial membranes while that of Mg-ATPase was on the inner surface or matrix side of the inner membrane. Those localization was not altered by the difference in temperature and the duration of storage.

Animals↗

[3H]RX 821002 in human dorsolateral prefrontal cortex: no changes in postmortem tissue from subjects with schizophrenia.

One of the major differences between the atypical antipsychotic drugs clozapine and olanzapine is that clozapine has a two-fold higher affinity for the alpha(2)-adrenoreceptors. As clozapine can have therapeutic benefits in individuals that do not respond to other antipsychotic drugs, this raises the possibility that changes in the alpha(2)-adrenoreceptors could be a marker for a predisposition to treatment resistance. A methodology has been optimised to measure the binding of [3H]RX 821002 to alpha(2)-adrenoreceptors in human postmortem CNS and has shown that these receptors are not altered in Brodmann's area 9 from subjects with schizophrenia. These data add to those of one other study that showed the alpha(2)-adrenoreceptors were not altered in Brodmann's area 10 and the hippocampus from subjects with schizophrenia, and do not support the hypothesis that changes in alpha(2)-adrenoreceptors are a marker for treatment resistance in schizophrenia.

Adrenergic alpha-2 Receptor Antagonists↗

Essential tremor associated with pathologic changes in the cerebellum.

BACKGROUND: Although essential tremor (ET) is one of the most common neurologic disorders, there have been few postmortem studies. We recently reported postmortem changes (torpedoes and Bergmann gliosis) in the cerebellar cortex in a few ET cases. OBJECTIVE: To describe more extensive postmortem changes in the cerebellum in another ET case. DESIGN: Case report. RESULTS: A 90-year-old woman had a 30-year history of ET. At postmortem examination, there was segmental loss of Purkinje cells, presence of torpedoes, and Bergmann gliosis in the cerebellar cortex. Moreover, there were extensive changes in the dentate nucleus, in the form of neuronal loss, neuronal atrophy, microglial clusters, and reduction in the number of efferent fibers (ie, pallor of the hilum). CONCLUSIONS: The brain in the current case exhibited more marked cerebellar pathologic features than noted in previously reported ET cases and thereby extends the described cerebellar findings in this common, yet pathologically poorly characterized, neurologic disorder.

Aged, 80 and over↗

Cellular changes in the postmortem hippocampus in major depression.

BACKGROUND: Imaging studies report that hippocampal volume is decreased in major depressive disorder (MDD). A cellular basis for reduced hippocampal volume in MDD has not been identified. METHODS: Sections of right hippocampus were collected in 19 subjects with MDD and 21 normal control subjects. The density of pyramidal neurons, dentate granule cell neurons, glia, and the size of the neuronal somal area were measured in systematic, randomly placed three-dimensional optical disector counting boxes. RESULTS: In MDD, cryostat-cut hippocampal sections shrink in depth a significant 18% greater amount than in control subjects. The density of granule cells and glia in the dentate gyrus and pyramidal neurons and glia in all cornv ammonis (CA)/hippocampal subfields is significantly increased by 30%-35% in MDD. The average soma size of pyramidal neurons is significantly decreased in MDD. CONCLUSION: In MDD, the packing density of glia, pyramidal neurons, and granule cell neurons is significantly increased in all hippocampal subfields and the dentate gyrus, and pyramidal neuron soma size is significantly decreased as well. It is suggested that a significant reduction in neuropil in MDD may account for decreased hippocampal volume detected by neuroimaging. In addition, differential shrinkage of frozen sections of the hippocampus suggests differential water content in hippocampus in MDD.

Adult↗

Change in the postmortem formation of hypostasis in skin preparations 100 micrometers thick.

Twenty-three paired skin samples from 19 autopsies without putrefaction were taken from areas of livor mortis that (1). did not blanch with finger pressure and (2). blanched with strong pressure by tweezers. Three-dimensional microscopic viewing of 100-microm benzidine-stained skin sections demonstrated small blood vessels filled with red blood cells. The diameters of the clumps of red blood cells were greater in the sections from non-blanched areas than in the blanched areas, suggesting that fixation of hypostasis soon after death depends on sedimentation of intravascular red blood cells and passive dilatation of small vessels rather than on postmortem hemolysis.

Adolescent↗

Cytotoxic T lymphocyte activity and cytokine expression in calves vaccinated with formalin-inactivated bovine respiratory syncytial virus prior to challenge.

The development of effective, safe vaccines for human and bovine respiratory syncytial virus (RSV) has been problematic. Inactivated RSV vaccines are of variable efficacy; poor efficacy may be related to induction of ineffective cell-mediated immunity (CMI). To characterize CMI in calves vaccinated with formalin inactivated (FI) BRSV, 11 calves were vaccinated twice with FI-BRSV (n=5) or mock vaccine (n=6) at a 2 week interval and challenged 1 month later. Prior to challenge a cannula was placed in the efferent lymphatic of the caudal mediastinal lymph node of each calf; lymph derived lymphocytes (LDL) were collected for analysis of CMI. Cytotoxic T lymphocyte (CTL) activity by LDL and/or peripheral blood mononuclear cells (PBMC) was measured by 51Cr release on days 5, 7, 9, and 10 post-challenge. Messenger RNA for interferon gamma (IFN-gamma), interleukin 2 (IL-2) and IL-4 was measured on days 0-10 by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) of RNA of LDL. BRSV-specific IFN-gamma production by PBMC was measured on days 0 and 10 by ELISA. Clinical signs and postmortem changes following challenge were evaluated. There was no difference between groups in clinical signs, postmortem changes, CTL activity, cytokine message expression, or IFN-gamma production. For both groups, percentage lysis by CTL peaked on days 7-10 and ranged from 11 to 25%. Failure of vaccination to prevent disease following challenge was likely associated with failure to prime for improved CMI responses.

Animals↗

Does the sequence of onset of rigor mortis depend on the proportion of muscle fibre types and on intra-muscular glycogen content?

We examined the postmortem changes in the levels of ATP, glycogen and lactic acid in two masticatory muscles and three leg muscles of rats. The proportion of fibre types of the muscles was determined with NIH image software. The ATP levels in the white muscles did not decrease up to 1 h after death, and the ATP levels 1 and 2 h after death in the white muscles were higher than those in the red muscles with a single exception. The glycogen level at death and 1 h after death and the lactic acid level 1 h after death in masticatory muscles were lower than in the leg muscles. It is possible that the differences in the proportion of muscle fibre types and in glycogen level in muscles influences the postmortem change in ATP and lactic acid, which would accelerate or retard rigor mortis of the muscles.

Adenosine Triphosphate↗