Biomedical subjects

K Opeskin

Publications and source records attributed to K Opeskin.

At least 19 recordsLinked to original sources

PubMed2000

Serotonin(2A) receptors are reduced in the planum temporale from subjects with schizophrenia.

[(3)H]ketanserin binding to 5HT(2A) receptors was measured in the left planum temporale (sensory speech cortex) from schizophrenic and non-schizophrenic (control) subjects using both particulate membranes and tissue sections. There was a significant decrease in the affinity of [(3)H]ketanserin binding to particulate membranes from schizophrenic subjects who were treated with phenothiazines up to death. Adding 2nM chlorpromazine to brain tissue from control subjects caused a similar decrease in the affinity of [(3)H]ketanserin binding to particulate membranes. This suggests that the decrease in affinity observed in the phenothiazine-treated subjects was due to residual drugs. In addition, there was a significant decrease in the density of [(3)H]ketanserin binding in both particulate membranes and tissue sections from schizophrenic subjects which did not appear to be due to residual antipsychotic drugs. Analysis of the laminar distribution of 5HT(2A) receptors showed that this decrease was greatest in cortical layer III. The decrease in the density of 5HT(2A) receptors was significant whether schizophrenic subjects were receiving phenothiazines or haloperidol at the time of death, and there was no correlation between the last recorded dose of antipsychotic drug and 5HT(2A) receptor density. These data suggest that a decrease in the density of 5HT(2A) receptors in the planum temporale may be associated with the pathology of schizophrenia.

Adolescent↗

PubMed2000

Does cardiac conduction pathology contribute to sudden unexpected death in epilepsy?

Heart weights have been reported to be increased in those dying suddenly and unexpectedly from epilepsy (SUDEP) and it has been suggested that cardiac pathology including cardiac conduction pathology and coronary artery atheroma may contribute to SUDEP. The purpose of this study was to perform a detailed controlled study of the microscopic pathology of the cardiac conduction system in SUDEP cases, in addition to assessing coronary artery atheroma and other cardiac pathology. The hearts of ten SUDEPs and ten control subjects (no history of epilepsy and a cause of death not primarily cardiac) were examined macroscopically and microscopically by two pathologists blinded to the patient group. Morphological abnormalities of the cardiac conduction system that could have possibly contributed to death were not increased in the SUDEP group (four cases showed such changes in the SUDEP group vs. six in the control). There was no significant difference between the maximal percentage coronary artery stenoses between the two groups and no increased prevalence of other cardiac pathology in the SUDEP group. However, since subtle abnormalities of the conduction system were identified in some of the epileptic deaths, it is still feasible that these may contribute to death by causing cardiac arrhythmia, when associated with apnoea, bradycardia or other cardiac arrhythmia related to an epileptic seizure.

Adolescent↗

PubMed2000

Muscarinic1 and 2 receptor mRNA in the human caudate-putamen: no change in m1 mRNA in schizophrenia.

Studies using tissue obtained at autopsy suggest that changes in cholinergic neurons could be important in the pathology of schizophrenia.1-4 We have previously reported a decrease in [3H]pirenzepine binding5 and [3H]AF-DX 384 binding6 to caudate-putamen (CP) from subjects who had schizophrenia. Under the conditions chosen, [3H]pirenzepine would predominately bind to muscarinic1 (M1) and muscarinic4 (M4) receptors,7whereas [3H]AF-DX 384 would mainly bind to muscarinic2 (M2) and M4 receptors.8 Given the relative concentrations of M1, M2 and M4 receptors in the human CP and the magnitude of the decreases in radioligand binding in schizophrenia, our results most likely reflected a change in the density of M1 and M2 receptors in the CP from the schizophrenic subjects. In situ hybridisation has now been used to determine levels of m1 and m2 mRNA in CP from 14 schizophrenic and 16 control subjects previously used for radioligand binding. m2 mRNA in the CP from the schizophrenic and control subjects was below the sensitivity of in situhybridisation. There was no difference in the levels of m1 mRNA in CP from schizophrenic and control subjects (mean +/- SEM: 103 +/- 16 vs106 +/- 17 fmol [35S]oligonucleotide probe g-1estimated tissue equivalents, P = 0.91). In conclusion, data from our radioligand binding studies show decreases in [3H]pirenzepine binding that are likely to reflect a decrease in the density of M1 receptors in CP from schizophrenic subjects. Our data in this study show the absence of a concomitant change in mRNA coding for that receptor.

Adult↗

PubMed2000

Sudden unexpected death in epilepsy in Victoria.

Sudden unexpected death in epilepsy (SUDEP) refers to sudden unexpected death in patients with epilepsy in whom autopsy fails to reveal an anatomic or toxicological cause of death. The purpose of this study was to examine associated factors and mechanisms relating to SUDEP in Victoria. The study was a retrospective study based on data from questionnaires completed by treating doctors and coronial files including police reports of death, autopsy and toxicology reports. The deaths were of people with epilepsy in Victoria that were referred to the coroner between 1991 and 1997. There were 15,751 coronial autopsies of which 357 had epilepsy and 50 (14%) were SUDEPs. The SUDEP rate was approximately 1 per 3000 epileptics per year. This study suggested the following associations: young age, tonic-clonic seizures, seizure frequency greater than 10/year, duration of epilepsy greater than 10 years, mental retardation, psychiatric disease and alcohol abuse. Antiepileptic drug (AED) compliance was rated by treating doctors as good in 24 cases. One or more postmortem AED drug levels was subtherapeutic in 30 of 50 cases. Only 5 were receiving psychotropic drugs; only 1 of these was receiving more than one of these drugs. A history of recent unusually stressful life event was present in only 4 cases. At least 11 showed evidence of terminal seizure, and the majority of events occurred in sleep. These observations support the hypothesis that seizures are the mechanism of many cases of SUDEP. The associations observed were largely in agreement with previous studies. However, seizure frequency was greater and duration of epilepsy greater than most previous studies. The role of factors such as AED compliance, psychotropic drug prescription and recent unusually stressful life event is less clear. This highlights the need for case-control studies of risk factors for SUDEP.

Adolescent↗

PubMed2000

Spontaneous rupture of the liver associated with a primary angiosarcoma: case report.

A case of fatal spontaneous rupture of the liver caused by primary angiosarcoma is described. Spontaneous rupture of the liver is a rare clinical and pathological entity associated with high morbidity and mortality rates. Possible causes include infections such as hydatid disease, infiltrating conditions such as amyloidosis, inflammatory disorders such as the vasculitides, malignant and benign tumors, and tumorlike conditions. As in the case presented, the finding of a ruptured liver raises the possibility of blunt abdominal trauma, and the circumstances and scene should be assessed. The possibility of terminal resuscitation attempts should also be considered as a possible cause.

Autopsy↗

PubMed2000

Prolactin levels in sudden unexpected death in epilepsy.

PURPOSE: To assess serum prolactin levels in sudden unexpected death in epilepsy (SUDEP) and control groups to test the hypothesis that if seizures occur routinely as a terminal event in SUDEP, then raised prolactin levels may be an indicator of terminal seizure. METHODS: Blood was taken for measurement of prolactin levels from subjects with SUDEP and three control groups. The control groups were those with epilepsy dying from causes other than epilepsy (e.g., ischemic heart disease or injuries), physiologically stressed individuals without epilepsy (they were admitted to the hospital after an acute illness and died after several hours to 3 days), and nonepileptic rapid deaths (these people collapsed suddenly and died at the scene). In the SUDEP group, evidence for terminal seizure was considered to be at least one of the following: body found half on, half off the bed, or urinary incontinence at the scene, or bitten lips or tongue at autopsy. RESULTS: There was evidence for terminal seizure at the scene or at autopsy in four of the 10 SUDEP cases. Serum prolactin levels were not significantly increased in the SUDEP group compared with the controls. None of the SUDEP subjects, including those with clinical evidence of a terminal seizure, had high prolactin levels characteristic of those observed after seizures in living subjects. CONCLUSIONS: Prolactin levels are not raised in SUDEP, even if there is evidence of terminal seizure. As prolactin takes 15-20 min to peak after a seizure in life, there may be insufficient time for a prolactin increase to occur in SUDEP. Thus prolactin levels cannot be used to determine if a deceased individual with epilepsy had a seizure or to answer the broad question whether SUDEP is always associated with a terminal seizure.

Adolescent↗

PubMed2000

Postmortem investigation of lamotrigine concentrations.

Lamotrigine is a relatively new anticonvulsant. Therapeutic plasma concentrations generally range from 1 to 4 mg/L, although several studies have shown that good control of epilepsy has been achieved with concentrations reaching 10 mg/L generally, with little toxicity. In overdose, however, the drug has been linked to ECG changes that may suggest a possible arrythmogenic effect and hence cardiac toxicity. Lamotrigine has also been shown to cause encephalopathy and thus neurotoxicity. There is no information concerning postmortem lamotrigine concentrations and their interpretation. We describe lamotrigine concentrations in postmortem specimens including blood, liver, bile, vitreous humour, and urine from eight cases. A high performance liquid chromatography (HPLC) method is described with extraction procedures for the various tissues. Two possible groups were identified. The first being the "broader therapeutic" group with blood concentrations ranging from 0.9 to 7.2 mg/L and corresponding liver concentrations ranging from 16 to 36 mg/kg. The second being a "supratherapeutic" group with blood concentrations ranging from 20 to 39 mg/L and corresponding liver concentrations ranging from 53 to 350 mg/kg. Although none of the eight cases described were attributed to overdose by lamotrigine alone, the cause of death for one of the three cases in the "supratherapeutic" group was given as mixed drug toxicity. Cause of death for the remaining two cases in this group was reported as epilepsy. However, both these cases showed elevated concentrations of lamotrigine and both were co-medicated with valproic acid. Such co-administration has been shown in the literature to lead to elevated lamotrigine concentrations and a reduction in lamotrigine dose has been recommended. With such data, we highlight the importance of monitoring lamotrigine concentrations in cases co-medicated, particularly with valproic acid.

Adult↗

PubMed1999

Mitochondrial respiratory chain activity in the human brain as a function of age.

Age-associated changes in mitochondrial respiratory chain activity were investigated in human brain tissue collected at autopsy. Four brain regions, the frontal cortex, superior temporal cortex, cerebellum and putamen, were studied to map any regional variation. A significant decrease in cytochrome c oxidase activity was seen in all regions studied with increasing age (P<0.05). Although a small decrease in succinate dehydrogenase-cytochrome c oxidoreductase and NADH: ubiquinone oxidoreductase activities was observed, this was not statistically significant. This study has shown that the age-related fall in cytochrome c oxidase activity affects the frontal cortex, superior temporal cortex, cerebellum and putamen. The variation in the extent of age-related oxidative phosphorylation decline was striking. We hypothesize that individuals with more severe age-related decline may be predisposed to neuronal dysfunction, whereas individuals with well preserved oxidative phosphorylation may enjoy some degree of neuronal protection.

Adult↗

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

Comparison of antiepileptic drug levels in sudden unexpected deaths in epilepsy with deaths from other causes.

PURPOSE: (a) To compare postmortem antiepileptic drug (AED) levels in patients with sudden unexpected death in epilepsy (SUDEP) with those in a control group of subjects with epilepsy. If SUDEP patients more frequently had undetectable or subtherapeutic AED levels, this would suggest that compliance with AED treatment is poorer in this group and that poor compliance is a risk factor for SUDEP. (b) To determine whether a particular AED was detected more commonly in the SUDEP group, suggesting that this AED is associated with a higher risk of SUDEP. METHODS: A retrospective study of coronial cases was performed. Postmortem AED levels in 44 SUDEP cases and 44 control cases were compared. The control group consisted of epileptics who died of causes other than epilepsy, including natural disease (e.g., ischemic heart disease, accidents, and suicide). The AEDs measured included carbamazepine (CBZ), phenytoin, (PHT), valproate (VPA), phenobarbitone (PB), lamotrigine (LTG), clonazepam (CZP), and clobazam (CLB). The number of SUDEP and control cases in which CBZ only was detected were compared, as were the number in which PHT only was detected. RESULTS: Compared with the controls, the SUDEP group showed no difference in the number with no detectable AEDs (13 vs. 11), the number with subtherapeutic AEDs (10 vs. 13), and the number with therapeutic levels (21 in both groups). CBZ only was detected in 11 SUDEPs and 11 controls, and PHT only in five SUDEPs and 10 controls. CONCLUSIONS: Our study suggests the SUDEP group were no less compliant with AED treatment than the control group. This study does not support the hypothesis that poor compliance with AED treatment is a risk factor for SUDEP. There was no evidence that PHT or CBZ is associated with a higher risk of SUDEP.

Adolescent↗

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↗