Biomedical subjects

K Opeskin

Publications and source records attributed to K Opeskin.

At least 19 recordsLinked to original sources

PubMed1999

No change in the density of the serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex from subjects with schizophrenia.

Changes in serotonin receptors and the serotonin transporter have been reported in the dorsolateral prefrontal cortex from subjects with schizophrenia, an area of the brain thought to be important in the pathology of the illness. To further our understanding on how such changes could play a role in the pathology of the illness, in situ radioligand binding with autoradiography was used to measure the density of the serotonin1A receptor, the serotonin4 receptor and the serotonin transporter in the dorsolateral prefrontal cortex, obtained at autopsy, from 10 schizophrenic and 10 control subjects. The binding of [3H]8-OH-DPAT to serotonin1A receptor, [3H]GR113808 to the 5HT4 receptor and [3H]citalopram to serotonin transporter was not altered in subjects with schizophrenia. significantly, only in tissue from the control subjects was there a relationship between age and the density of the serotonin4 receptor in Brodmann's areas 8 (r = 0.71, P = 0.02) and 10 (r = -0.67, P = 0.03). Importantly, this confounding factor did not influence the comparison of the density of serotonin4 receptor in the tissue from the schizophrenic and control subjects. This study has failed to show a difference in the density of serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9 and 10) from subjects with schizophrenia. These data suggest that not all serotonergic markers are altered in the dorsolateral prefrontal cortex from schizophrenic subjects.

Carrier Proteins↗

PubMed1999

Changes in serotonin2A and GABA(A) receptors in schizophrenia: studies on the human dorsolateral prefrontal cortex.

Having shown a decrease in serotonin2A receptors in the dorsolateral prefrontal cortex (DLPFC) from schizophrenic subjects, we have now determined if this change was reflective of widespread changes in neurochemical markers in DLPFC in schizophrenia. In Brodmann's area (BA) 9 from 19 schizophrenic and 19 control subjects, we confirmed a decrease in the density of [3H]ketanserin binding to serotonin2A receptors in tissue from the schizophrenic subjects [39 +/- 3.3 vs. 60 +/- 3.6 fmol/mg estimated tissue equivalents (ETE); p < 0.005]. In addition, the density of [3H]muscimol binding to GABA(A) receptors was increased in the schizophrenic subjects (526 +/- 19 vs. 444 +/- 28 fmol/mg ETE; p < 0.02). [3H]YM-09151-2, N-[1-(2-thienyl)cyclohexyl]-3,4-[3H]piperidine, [3H]SCH 23390, [3H]mazindol, and N(G)-nitro-L-[3H]arginine binding to BA 9 did not differ between groups, and there was no specific binding of [3H]raclopride or 7-hydroxy-2-(di-n-[3H]propylamino)tetralin to BA 9 from either cohort of subjects. This suggests the density of dopamine D1-like and NMDA receptors, the dopamine transporter, and nitric oxide synthase activity are not altered in BA 9 from schizophrenic subjects. The selective nature of the changes in serotonin2A and GABA(A) receptors in DLPFC could indicate that these changes are involved in the pathology of schizophrenia.

Adult↗

PubMed1999

Adrenocortical insufficiency.

Primary adrenocortical insufficiency is a rare disease which may present with protean clinical symptoms and signs. At one end of the spectrum is the patient with a long clinical history with marked pigmentation and documented episodes of crises which may follow relatively minor viral illnesses. The other extreme is illustrated by patients with a rapid deterioration in health culminating in unexpected or unexplained death. In the latter instances, the forensic pathologist may well be involved, and the case will present a significant challenge to diagnosis. We report 5 cases of primary and secondary adrenocortical insufficiency seen at the Victorian Institute of Forensic Medicine in 1 year. One adult man presented as a case of sudden unexplained death. In 2 cases, the diagnosis of adrenocortical insufficiency was raised following postmortem examination and confirmed by the treating physician following further consultation. In the remaining 2 cases, the diagnosis was known prior to postmortem examination and the diagnosis confirmed.

Addison Disease↗

PubMed1999

Nontraumatic clostridial myonecrosis.

We describe three cases of nontraumatic clostridial myonecrosis seen at the Victorian Institute of Forensic Medicine. Nontraumatic clostridial myonecrosis is an uncommon and often fatal condition that requires immediate institution of appropriate medical and surgical therapy. It is most commonly caused by Clostridium perfringens and Clostridium septicum and is associated with gastrointestinal and hematologic malignancies, diabetes mellitus, and peripheral vascular disease. The clinical features include a rapidly evolving acute illness with severe pain, marked tachycardia, and brawny discoloration of the skin with bullae formation and crepitus, followed by hypotension and acute renal failure. Features at autopsy include reddish brown skin discoloration with bullae formation and necrotic skeletal muscle. Radiographs may be of use prior to the postmortem in detecting gas within the soft tissues. Gram stain and microbiologic culture are important in establishing a definitive diagnosis; although the major factors in suggesting the diagnosis are the recognition of the typical clinical history and macroscopic autopsy findings.

Abdominal Pain↗

PubMed1999

Irregular distribution of cytochrome c oxidase protein subunits in aging and Alzheimer's disease.

This study aims to investigate the cellular distribution of human cytochrome c oxidase (COX) subunit II (CII) and COX subunit IV (CIV) in Alzheimer's disease relative to control brains. The levels of CIV and CII proteins in the cerebellar Purkinje cells were reduced in age-matched controls relative to young controls and in the Alzheimer's disease group relative to both age-matched and young controls. Results suggest that these age-associated changes are more marked in Alzheimer's disease.

Aging↗

PubMed1998

The pathogenesis of Schmorl's nodes in relation to acute trauma. An autopsy study.

STUDY DESIGN: Seventy thoracolumbar spines from cadavers of individuals killed in motor vehicle accidents were examined pathologically and radiologically, particularly for the occurrence of acute Schmorl's nodes. OBJECTIVES: To document whether Schmorl's nodes occur acutely as a result of trauma. SUMMARY OF BACKGROUND DATA: Theories proposed to explain the pathogenesis of Schmorl's nodes include developmental, degenerative, traumatic, and disease influences. Few studies show a direct causal relation between a traumatic episode and acute Schmorl's node formation. METHODS: Thoracolumbar spines were removed at autopsy, underwent radiography in the anteroposterior and lateral planes, fixed, sagittally cut, and underwent radiography a second time. Pathologic and radiographic examinations were performed. RESULTS: Nine acute Schmorl's nodes were detected, most in association with other acute injuries to the spine. Most acute Schmorl's nodes were present in spines from individuals aged 11-30 years, with a male to female ratio of 9:1, and were localized to the T8-L1 region. Spines from motorcyclists showed the highest percentage of acute Schmorl's nodes. No acute Schmorl's nodes were detected radiologically. CONCLUSION: Schmorl's nodes do occur acutely as the result of a single traumatic episode, and are almost always associated with other acute spinal injury. The frequency and occurrence of acute Schmorl's nodes in motorcyclists suggest that axial loading is an important mechanism. Their predominance in the T8-L1 region suggests that this region is particularly susceptible to stress.

Acute Disease↗

PubMed1998

Disc herniations in the young and end-plate vascularity.

The objective of this study was to determine the nature of the persistence of remnants of the original nutritive vascular canals within the vertebral body and correlate their existence with end-plate "weak spots." The body-disc region of 20 lumbar vertebrae between the ages of birth and 22 years was examined histologically to study the vascularity of the end-plate cartilage and its fate at the end of vertebral growth. Observations indicate a regression of the vascular canals in the end-plate commencing in the first decade, with "scars" left by these canals visible as nodular areas. By the beginning of the third decade, herniation of the disc material into the weak spots was observed. It is apparent that these weak spots represent a route for the early formation of intrabody nuclear herniations at this age (Schmorl's nodes).

Adolescent↗

PubMed1998

Timing of early changes in brain trauma.

One hundred and fourteen fatal cases of brain trauma were examined prospectively; in 100 of these cases, death occurred within 48 hours of injury. The methods of injury included motor vehicle accidents (MVA), gunshot wounds, blunt instrument injuries, and falls. All cases showed subarachnoid and parenchymal hemorrhages. Paraffin sections were studied with hematoxylin and eosin (H&E) stain and also with special stains in selected slides. The cases were examined histologically before having exact clinical knowledge of the time of death. Eosinophilic neurons were noted in many cases surviving <1 hour after injury and increased in frequency and severity with time. These were most commonly seen in areas of contusion, the hippocampus, and the arterial boundary zones of the cerebral cortex. Neuronal incrustation was seen from 3 to 48 hours postinjury in areas of contusion. Axonal swelling and spheroids were seen in the white matter in areas of laceration and hemorrhage at 1 hour postinjury in many cases and continuing through all time periods. Glial swelling was seen in the subpial and subependymal regions and around hemorrhages from very early to 48 hours postinjury. Polymorphonuclear leukocytes (granulocytes) were present in the tissues at all time periods with increasing frequency over time. They were also found surrounding corpora amylacea in cases with <1 hour survival. Axonal swelling, eosinophilia of neurons, and incrustation of neurons were noted at earlier time periods than previously reported in the literature. Determining the time of injury based on histologic evidence is difficult. We believe that the data reported here will allow more accurate appreciation of timing of the early interval between brain trauma and death.

Adolescent↗

PubMed1998

Postmortem extravasation of blood potentially simulating antemortem bruising.

A case of florid postmortem extravasation of blood, potentially simulating antemortem bruising, is presented. A 98-year-old woman died in hospital, the cause of death being certified as congestive cardiac failure. After burial, it was apparent that the grave had been disturbed by crowbars and shovels. Exhumation was performed and autopsy revealed considerable apparent facial bruising as well as lacerations and fractures. There was no documentation by the medical or nursing staff of any injuries to the deceased preceding death. There was also no documentation of injury by the funeral directors. Subsequently, two men admitted to removing the body from the grave and mutilating it. Thus, what was apparently facial bruising was, in fact, postmortem extravasation of blood simulating antemortem bruising. The degree of extravasation was considered to be related to the severity of the injuries, loose subcutaneous tissues of the head and neck, and dependent position of the body upon return to the grave. This case demonstrates the degree of postmortem extravasation of blood that may occur in particular circumstances and may simulate antemortem bruising. In other circumstances, the postmortem extravasation of blood may well have led investigators to pursue inquiries regarding homicide.

Aged↗

PubMed1998

Vertebral artery trauma.

Vertebral artery trauma is not commonly seen by forensic pathologists. The experience of vertebral artery trauma at the Victorian Institute of Forensic Medicine (30 cases) is summarized and reviewed in the light of the literature. Causes of vertebral artery trauma are discussed. In case 1, the history and timing of the injury raise the question as to whether the vertebral artery dissection occurred before the episode of trauma, that is, was spontaneous or resulted from trauma. Moreover, underlying vertebral artery disease was present, raising the question as to how much trauma was needed to cause vertebral artery dissection. In case 2, despite the history of head/neck trauma, a neurosurgeon considered the subarachnoid hemorrhage was spontaneous, due most likely to ruptured saccular aneurysm or arteriovenous malformation. In case 3, the vertebral artery rupture was not diagnosed in the setting of multiple injuries. Case 4 is an example of prolonged survival with delayed onset of symptoms following vertebral artery trauma. Case 5 is an example of the not uncommon scenario of homicidal vertebral artery trauma accounting for basal subarachnoid hemorrhage, rapid collapse and death. Cases 1 and 4 indicate that relatively normal activity may be possible following vertebral artery trauma in some cases (at least for a time). Cases 1 and 4 are also examples of intracranial vertebral artery dissection.

Adult↗

PubMed1998

Confirmation of the diagnosis of schizophrenia after death using DSM-IV: a Victorian experience.

OBJECTIVE: This study examines the reliability of antemortem diagnoses of schizophrenia using DSM-IV criteria. METHOD: The case histories of 83 subjects with a provisional diagnosis of schizophrenia at autopsy were retrospectively reviewed using a semi-structured chart review and application of DSM-IV criteria. Agreement between antemortem and postmortem diagnoses of schizophrenia was examined, as well as the concordance between DSM-IV diagnoses and previously obtained diagnoses using DSM-III-R and ICD-10 criteria for schizophrenia. RESULTS: According to DSM-IV, 30.1% of cases did not have schizophrenia, compared to 36.1% using DSM-III-R criteria and 51.8% of cases using ICD-10 criteria. Concordance between DSM-IV and DSM-III-R diagnoses of schizophrenia was excellent (kappa = 0.81), but only fair between DSM-IV and ICD-10 (kappa = 0.57). Of the cases that did not meet the formal criteria for schizophrenia, the majority were reassigned diagnoses of schizoaffective disorder and affective disorder. CONCLUSIONS: The use of human brain tissue in postmortem studies of schizophrenia must be linked to standardised diagnostic assessment procedures. Diagnoses can be upgraded with the development of new criteria, providing sufficient clinical data is available in case histories.

Adult↗

PubMed1997

Changes in protein kinase C and adenylate cyclase in the temporal lobe from subjects with schizophrenia.

Changes in G-protein linked neurotransmitter receptors have been reported in a number of regions of the brain of schizophrenic subjects. These changes, if functional, could cause a change in proteins such as protein kinase C (PKC) and adenylate cyclase (AC) which are important components of the G-protein linked second messenger cascades. We therefore used autoradiography to measure the distribution and density of [3H]phorbol ester binding to PKC and [3H]forskolin binding to AC in tissue obtained at autopsy from schizophrenic and non-schizophrenic subjects (Controls). There were significant decreases in the density of PKC in the parahippocampal gyrus (687 +/- 60 vs. 885 +/- 51 fmol/mg TE; mean +/- SEM; p < 0.01) and in AC in the dentate gyrus (75 +/- 4.9 vs. 92 +/- 6.5, p < 0.05) from the schizophrenic subjects. These data could indicate that changes in neurotransmitter receptors in the hippocampus from subjects with schizophrenia could have resulted in a change in their associated second messenger systems.

Adenylyl Cyclases↗

PubMed1997

[3H]raclopride binding to brain tissue from subjects with schizophrenia: methodological aspects.

The binding of [3H]raclopride to particulate membrane and frozen sections (with quantitative autoradiography) from the caudate-putamen, obtained at autopsy from schizophrenic and non-schizophrenic subjects, was measured. The affinity of [3H]raclopride to particulate membrane was significantly decreased in the schizophrenic compared to non-schizophrenic subjects. The density of [3H]raclopride binding to tissue from subjects with schizophrenia was increased, unchanged or decreased depending on the methodology used. Finally, there was an age-dependent decrease in [3H]raclopride binding in the frozen sections from the caudate-putamen of the non-schizophrenic subjects. This age-dependent decrease was not apparent using particulate membrane from schizophrenic or non-schizophrenic subjects or tissue sections from the schizophrenic subjects. We conclude that the binding of [3H]raclopride is dependent on methodology and therefore data from in vitro and in vivo studies using this drug should be interpreted with caution.

Adult↗

PubMed1997

Traumatic carotid artery dissection.

Traumatic carotid artery dissection is rarely seen as a cause of death in the forensic setting. Three cases of traumatic carotid artery dissection that demonstrate many of the typical features are presented. There is usually a history of some violent trauma to the head or neck, motor vehicle accidents being the commonest cause. The carotid artery may be injured anywhere from the common carotid portion to the cavernous sinus, resulting in infarction of the corresponding cerebral hemisphere. Clinically, symptoms may include loss of consciousness, hemiparesis, aphasia, and Horner's syndrome, these typically occurring after an interval of hours to days. Carotid artery injury may not be associated with evidence of external injury and initially may go undetected or may be misinterpreted in the setting of associated neck or head trauma. The commonest mechanisms are thought to be blunt neck trauma and neck hyperextension. The cases presented highlight the importance of early diagnosis if surgery is to be possible to avoid a fatal outcome.

Accidents, Traffic↗

PubMed1996

Neither protein kinase C nor adenylate cyclase are altered in the striatum from subjects with schizophrenia.

Dopamine (DA) D2 receptors which act by modulating second messenger pathways that include protein kinase C (PKC) and adenylate cyclase (AC) have been repeatedly shown to be increased in striatum from subjects with schizophrenia. Therefore it seemed possible that chronic up-regulation of DA-D2 receptors in the schizophrenic brain could result in a change in either of these two proteins. Hence we measured PKC and AC in striatum from 20 schizophrenic subjects and 20 non-schizophrenic subjects by quantitative autoradiography and could show no difference in the density of either PKC (436 +/- 35 vs. 485 +/- 29 fmol/mg tissue equivalents (TE), mean +/- SEM) or AC (77 +/- 9 vs. 80 +/- 7 fmol/mg TE) in the tissue from schizophrenic compared to the non-schizophrenic subjects. Thus, these data do not support the hypothesis that PKC or AC are changed in the schizophrenic brain.

Adenylyl Cyclases↗

PubMed1996

Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine.

[3H]paroxetine binding to membrane from hippocampus, obtained at autopsy, from 24 schizophrenic and 24 non-schizophrenic subjects has been measured. The affinity of [3H]paroxetine binding to hippocampal membrane was decreased in subjects with schizophrenia (Kd = 0.50 +/- 0.04 vs. 0.24 +/- 0.02nM; mean +/- S.E.M. p < 0.001) but was not different in schizophrenic subjects who had or had not committed suicide (Kd = 0.50 +/- 0.07 vs. 0.50 +/- 0.04nM). The density of [3H]paroxetine binding sites did not differ between the schizophrenic and non-schizophrenic subjects. For the schizophrenic subjects, there was no relationship between ante-mortem neuroleptic drug treatment and [3H]paroxetine binding to the hippocampal membrane. Finally, this study has shown that neuroleptic drug treatment of rats does not alter [3H]paroxetine binding to the hippocampal membranes. Thus, it would seem that the changes in the affinity of [3H]paroxetine binding to the hippocampus of schizophrenic subjects are not likely to be due to neuroleptic drug treatment but may be involved in the pathology of the illness.

Adult↗

PubMed1996

Serotonin2 receptors and the serotonin transporter in the schizophrenic brain.

The binding of [3H]paroxetine and [3H]ketanserin to particulate membranes from frontal cortex of subjects who had or did not have schizophrenia was measured as was [3H]paroxetine binding to particulate membranes from the hippocampus and caudate nucleus. There was no change in either the affinity or density of [3H]ketanserin binding to membranes from the frontal cortex of subjects who had schizophrenia. Similarly, there was no difference in the density of [3H]paroxetine binding to membranes from subjects who had or did not have schizophrenia. The affinity of [3H]paroxetine binding in the frontal cortex and putamen did not differ in subjects who had schizophrenia. By contrast, there was a significant decrease in the affinity of [3H]paroxetine binding to the hippocampal membrane from subjects who had schizophrenia (0.40 +/- 0.06 nM vs 0.26 +/- 0.02 nM; p < 0.05). Furthermore, this difference was more apparent in the subjects who had schizophrenia and committed suicide (0.49 +/- 0.09 nM) than it was in those who had schizophrenia but did not commit suicide (0.32 +/- 0.09 nM). As [3H]ketanserin binds to the serotonin2 receptor our data suggest that this receptor is not changed in the Brodmann's area 9 of the frontal cortex. By contrast, [3H]paroxetine binds to the serotonin transporter and therefore our data suggest that the serotonin transporter is altered in the hippocampus of subjects with schizophrenia.

Adolescent↗

PubMed1996

Cerebral amyloid angiopathy. A review.

Cerebral amyloid angiopathy (CAA) is a condition characterized by amyloid deposition in cerebral blood vessels. It occurs most frequently in association with clinical Alzheimer's disease but also occurs in some nondemented elderly people. CAA is a cause of spontaneous cerebral hemorrhage and may therefore present as a sudden unexpected death in an elderly person. The amyloid is deposited in cortical blood vessels, and on hematoxylin-eosin sections takes the form of pink hyaline thickening of arteries and arterioles, often with narrowing of the lumina. For diagnosis apple-green birefringence after Congo red staining is the most widely practiced and reliable tool. CAA-related hemorrhage may also occur in any lobe of the cerebrum close to the external surface and may occur at multiple sites and at the same or different times. CAA-related hemorrhage may occur in the setting of trauma necessitating distinction between the two and raising the question of whether it precipitated trauma or vice versa. Usually CAA-related hemorrhage is infrequent in sites where traumatic hemorrhages occur, and traumatic hemorrhages are often associated with other hemorrhages in sites typical for trauma. Five cases demonstrating many of the clinical and pathological features of CAA-related hemorrhage are presented. In two of the five cases, the hemorrhage followed trauma, suggesting that trauma as a precipitating factor for CAA-related hemorrhage may be more common than is generally recognized. CAA-associated hemorrhage should be considered in the differential diagnosis of cerebral hemorrhage in the elderly whether or not dementia is present.

Aged↗