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E Perry

Publications and source records attributed to E Perry.

At least 19 recordsLinked to original sources
PubMed2001

Nicotinic receptor abnormalities in Alzheimer's disease.

Loss of cortical nicotinic acetylcholine receptors with high affinity for agonists (20-50%) in patients with Alzheimer's disease is a common finding. Recent immunochemical analyses indicate that this deficit is predominantly associated with the loss of alpha4 subunits (30-50%), although modest reductions of alpha3 may occur in some individuals (25-29%). No reduction of beta2 subunit protein expression or levels of alpha3 and alpha4 messenger RNA has been reported. Decline in cortical [(125)I]alpha-bungarotoxin binding and alpha7 protein expression does not appear to be as extensive or widespread as the loss of alpha4 (0-40%), with no reduction in messenger RNA expression. In the thalamus, there was a trend for reduced [(3)H]nicotine binding in the majority of nuclei (0-20%) in Alzheimer's disease; however, there was a significant decline in [(125)I]alpha-bungarotoxin binding in the reticular nucleus. In the striatum [(3)H]nicotine binding was reduced in Alzheimer's disease, and although neuroleptic medication accentuated this change, it occurred in those free of neuroleptics. Changes in nicotinic acetylcholine receptors in Alzheimer's disease are distinct from those in normal aging and are likely to contribute to clinical features and possibly neuropathology.

Aged↗
PubMed2000

Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases.

Human brain ageing is associated with reductions in a variety of nicotinic receptors subtypes, whereas changes in age-related disorders including Alzheimer's disease or Parkinson's disease are more selective. In Alzheimer's disease, in the cortex there is a selective loss of the alpha4 (but not alpha3 or 7) subunit immunoreactivity and of nicotine or epibatidine binding but not alpha-bungarotoxin binding. Epibatidine binding is inversely correlated with clinical dementia ratings and with the level of Abeta1-42, but not related to plaque or tangle densities. In contrast, alpha-bungarotoxin binding is positively correlated with plaque densities in the entorhinal cortex. In human temporal cortex loss of acetylcholinesterase catalytic activity is positively correlated with decreased epibatidine binding and in a transgenic mouse model over expressing acetylcholinesterase, epibatidine binding is elevated. In Parkinson's disease, loss of striatal nicotine binding appears to occur early but is not associated with a loss of alpha4 subunit immunoreactivity. Tobacco use in normal elderly individuals is associated with increased alpha4 immunoreactivity in the cortex and lower densities of amyloid-beta plaques, and with greater numbers of dopaminergic neurons in the substantia nigra pars compacta. These findings indicate an early involvement of the alpha4 subunit in beta-amyloidosis but not in nigro-striatal dopaminergic degeneration.

Acetylcholinesterase↗
PubMed2000

CNS acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory.

Certain Lamiaceous and Asteraceous plants have long histories of use as restoratives of lost or declining cognitive functions in western European systems of traditional medicine. Investigations were carried out to evaluate human CNS cholinergic receptor binding activity in extracts of those European medicinal plants reputed to enhance or restore mental functions including memory. Ethanolic extracts were prepared from accessions of these plants and a number of other species related by genus. Amongst the plant extracts screened for contents able to displace [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic receptors and muscarinic receptors, respectively in homogenates of human cerebral cortical cell membranes, the most potent extracts, prepared from one accession of Melissa officinalis, three Salvia species and Artemisia absinthium had IC50 concentrations of < 1 mg/ml. The displacement curves of some extracts were comparable with that of carbamylcholine chloride, a potent acetylcholine analogue. Choline, a weak nicotinic ligand (IC50 = 3 x 10(-4) M) was found in extracts of all plants studied at concentrations of 10(-6)-10(-5) M. These concentrations could not account for not more than 5% of the displacement activity observed. Some extracts displayed differential displacement at nicotinic and muscarinic acetylcholine receptors, with M. officinalis 0033 having the highest [3H]-(N)-nicotine displacement value and Salvia elegans with the highest [3H]-(N)-scopolamine displacement value. There was also considerable variation in cholinoreceptor interactions between different accessions of a single plant species. Although most plant extracts screened showed some nicotinic and muscarinic activity, only some showed dose-dependent receptor activity typical of materials with genuine cholinergic activity.

Asteraceae↗
PubMed2000

Nicotinic receptors in human brain: topography and pathology.

Brain nicotinic acetylcholine receptors (nAChR) are a class of ligand-gated channels composed of alpha and beta subunits with specific structural, functional and pharmacological properties. They participate in the physiological and behavioural effects of acetylcholine and mediate responses to nicotine. They are associated with numerous transmitter systems and their expression is altered during development and ageing as well as in diseases such as autism, schizophrenia, Alzheimer's disease, Parkinson's disease and Lewy body dementia. Nicotinic receptors containing a number of different subunits are highly expressed during early human development. Disorders believed to be associated with abnormal brain maturation involve deficits in both alpha4beta2, in the case of autism, and alpha7 possibly in addition to alpha4beta2 nAChRs in the case of schizophrenia. In ageing and age-related neurodegenerative disorders nAChR deficits are predominantly associated with alpha4-containing receptors, although some studies also indicate the involvement of alpha3 and alpha7 subunits. Whilst ageing appears to be associated with reductions in subunit mRNA as well as protein expression, in Alzheimer's disease only protein loss is apparent. Nicotinic therapy may be of benefit in a number of neurological conditions, however studies evaluating further both the distribution of specific subunit involvement and the correlation of nAChR deficits with clinical symptoms are required to inform therapeutic strategy.

Brain Chemistry↗
PubMed2000

Nicotinic receptors in dementia of Alzheimer, Lewy body and vascular types.

OBJECTIVES: Comparisons were made of nicotinic receptors in 3 major forms of dementia in old age. Although it is well established the involvement of nicotinic receptors in Alzheimer's disease (AD), their status in the other two main causes of dementia in old age-dementia with Lewy bodies (DLB) and vascular dementia (VaD) is not widely reported. METHODS: Temporal cortex was examined for epibatidine and alpha-bungarotoxin binding, and immunoreactivity of alpha4 and alpha7 nAChR subunits. RESULTS: There were selective abnormalities in nicotinic receptor subtypes in the disorders examined. In AD there is a loss of high affinity receptor binding, reflecting a selective loss of alpha4 subunit, but no change in alpha7 subunits. Similar abnormalities in ligand binding are also apparent in DLB. In the VaD series, there was no overall loss of epibatidine binding or immunoreactivity for alpha4 or alpha7 subunits. CONCLUSIONS: Loss of cortical receptor alpha4 subunit appears to be a characteristic feature of neurodegenerative dementia but not dementia of vascular origin. Since nicotinic receptors control cerebral vasodilation, the relative integrity of the receptors in VaD may auger well for nicotinic therapy in this disorder in which there is a cholinergic abnormality, to judge by the loss of the presynaptic enzyme.

Aged↗
PubMed2000

Delusions associated with elevated muscarinic binding in dementia with Lewy bodies.

The relation between disturbances of cholinergic neurotransmission and delusions (DELs) has not been investigated in degenerative dementias such as dementia with Lewy bodies (DLB). A cohort of dementia patients were assessed with standardized clinical evaluations (including the Columbia University Scale for Psychopathology in Alzheimer's Disease), which were repeated annually until death. DLB was confirmed neuropathologically in 21 patients. Neurochemical evaluation included M1 receptor autoradiography (pirenzepine binding), biochemical measurement of choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) histochemistry in brain regions hypothesized to be involved in the genesis of psychosis. Compared with 11 age-matched controls, CHAT and pirenzepine levels were most extensively reduced in the temporal and parietal neocortex of DLB patients. In Brodmann area 36, DELs were significantly associated with elevated pirenzepine binding (131.0 vs 93.5, t = 2.7), whereas visual hallucinations were associated with significant reductions in ChAT (1.7 vs 2.5, t = 2.5). There were no significant associations with other areas or with cholinesterase. Although DELs and visual hallucinations were both linked with disturbances in cholinergic neurotransmission, the nature of the associations was different. Upregulation of the postsynaptic muscarinic receptor may be central in the genesis of DELs, with important treatment implications.

Aged↗
PubMed1999

Dementia with Lewy bodies: choline acetyltransferase parallels nucleus basalis pathology.

The biological substrate underlying the reduced cortical choline acetyltransferase (ChAT) in dementia with Lewy bodies (DLB) is incompletely understood. We compared cortical ChAT levels with Lewy body densities and neuronal loss in the nucleus basalis of Meynert (nbM) and cerebral cortex in six DLB, seven Alzheimer's disease (AD), and six control cases. We found greater neuronal loss in the nbM in DLB compared to AD (U = 9.500, p = 0.049). Mean ChAT levels in the cortex were lower in dementia patients than controls (t = 17.500, p = 0.001), and DLB cases had slightly lower ChAT levels than AD cases, but this difference was not significant (t = -0.332, p = 0.746). Overall, cortical ChAT levels correlated inversely with neuronal loss in the nbM (Spearman rank correlation coefficient = -0.53). The correlation between ChAT level and the combined factor of nbM LBs and neuronal loss was -0.59. A similar correlation between ChAT level and the combined factor of nbM neurofibrillary tangles and neuronal loss was -0.72. The correlation between ChAT and the combined factor of nbM LBs and neuronal loss was -0.81 when AD cases were excluded from the analysis. Local cortical pathology was not related to ChAT level. We conclude that neuronal loss and Lewy body formation in the nbM may contribute to the reduction in cortical ChAT in DLB.

Aged↗
PubMed1999

Acetylcholine in mind: a neurotransmitter correlate of consciousness?

The cholinergic system is one of the most important modulatory neurotransmitter systems in the brain and controls activities that depend on selective attention, which are an essential component of conscious awareness. Psychopharmacological and pathological evidence supports the concept of a 'cholinergic component' of conscious awareness. Drugs that antagonize muscarinic receptors induce hallucinations and reduce the level of consciousness, while the nicotinic receptor is implicated as being involved in the mechanism of action of general (inhalational) anaesthetics. In degenerative diseases of the brain, alterations in consciousness are associated with regional deficits in the cholinergic system. In Alzheimer's disease (AD), there is a loss of explicit (more than implicit) memory and hypoactivity of cholinergic projections to the hippocampus and cortex, while the visual hallucinations experienced by subjects with Dementia with Lewy bodies (DLB) are associated with reductions in neocortical ACh-related activity. In Parkinson's disease, the additional loss of pedunculopontine cholinergic neurones, which control REM (rapid eye movement) sleep or dreaming, is likely to contribute to REM abnormalities, which also occur in DLB. Widespread basal-forebrain and rostral brainstem cholinergic pathways, which include converging projections to the thalamus, appear to be located strategically for generating and integrating conscious awareness. Alleviation of a range of cognitive and non-cognitive symptoms by drugs that modulate the cholinergic system, which are being developed for the treatment of AD and related disorders, could be caused by changes in consciousness.

Acetylcholine↗
PubMed1999

Reply to Holscher

Explore the source record for details and available documents.

Journal Article↗
PubMed1999

Neuronal nicotinic receptors in dementia with Lewy bodies and schizophrenia: alpha-bungarotoxin and nicotine binding in the thalamus.

Neuronal nicotinic receptors have been implicated in schizophrenia on the basis of the high incidence of tobacco smoking in patients, abnormalities in cytisine and alpha-bungarotoxin (alphaBGT) binding in the hippocampus, and linkage between auditory P50 deficits and the region of chromosome 15 coding the alpha7 subunit. In another disease associated with psychosis, dementia with Lewy bodies (DLB), in which visual hallucinations predominate, reductions in nicotine binding have been identified in various cortical and subcortical regions. We investigated both alphaBGT and nicotine binding autoradiographically in different thalamic nuclei in autopsy brain tissue from patients with schizophrenia and DLB. AlphaBGT binding in the reticular nucleus was moderately reduced (25%) in schizophrenia and more extensively reduced (50%) in DLB. There were no significant alterations in nicotine binding in schizophrenia, and in DLB, a trend towards moderate reductions in most nuclei reached significance in the lateral dorsal nucleus. It is concluded that widespread abnormalities of thalamic nicotine are not implicated in schizophrenia or DLB, but that reticular alphaBGT binding may be involved to a lesser and greater extent in the pathophysiology or psychopathology of both disorders.

Aged↗
PubMed1999

The relationship of rural persons' multidimensional health locus of control to knowledge of cancer, cancer myths, and cancer danger signs.

The purpose of the study was to determine if a relationship exists between multidimensional health locus of control and knowledge of breast cancer, prostate cancer, cancer myths, and danger signs. A descriptive correlational design was used. A convenience sample of 78 rural men and 79 rural women participated in the study. Participants completed three questionnaires: (a) the Cancer Danger Signs Questionnaire, (b) the Cancer Myths Questionnaire, (c) the Prostate Cancer Knowledge Test (completed by the men) and the Breast Cancer Knowledge Test (completed by the women). Results indicated that an internal score on the Multidimensional Health Locus of Control (MHLOC) scale did not predict knowledge of breast cancer in women, prostate cancer in men, cancer myths, or danger signs. Women who scored high on the Powerful Others subscale of the MHLOC had statistically significant high scores on knowledge of breast cancer, but not on cancer myths and danger signs. The MHLOC and its subscales did not predict knowledge of prostate cancer, cancer myths, or cancer danger signs for the male participants. The implications of these results for rural nursing practice and their relationship to previous research are discussed.

Adult↗
PubMed1999

Psychiatric morbidity in dementia with Lewy bodies: a prospective clinical and neuropathological comparative study with Alzheimer's disease.

OBJECTIVE: The literature reports considerable variation in the rates of psychiatric morbidity for patients with dementia with Lewy bodies. The authors intended to clarify the frequency of psychiatric morbidity in dementia with Lewy bodies and how it differs from probable Alzheimer's disease. METHOD: The study incorporated two groups--a clinical case register cohort (98 with dementia with Lewy bodies; 92 with Alzheimer's disease) and 80 (40 with dementia with Lewy bodies: 40 with Alzheimer's disease) prospectively studied, neuropathologically confirmed cases. Diagnoses were made by using the McKeith et al. consensus criteria for dementia with Lewy bodies and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Neuropathological diagnoses were made by using the consensus criteria for dementia with Lewy bodies and the Mirra et al. protocol for Alzheimer's disease. RESULTS: The occurrence of psychiatric symptoms was reported over 1 month. Hallucinations, depression, delusions, and delusional misidentification were all significantly higher for patients with dementia with Lewy bodies. The differences in frequency between dementia with Lewy bodies and Alzheimer's disease for auditory and visual hallucinations were especially pronounced for patients with mild cognitive impairment. The presence of psychiatric symptoms at presentation was a better discriminator between dementia with Lewy bodies and Alzheimer's disease than occurrence over the course of dementia. CONCLUSIONS: Delusional misidentification and hallucinations in the early stages of dementia may improve differentiation between patients with dementia with Lewy bodies and those with Alzheimer's disease and have important treatment implications.

Aged↗
PubMed1998

Therapeutic apheresis for babesiosis.

Infection with the tick-borne protozoa Babesia is becoming more common. Babesiosis is usually successfully treated with antibiotics but, in some cases, apheresis may also be indicated. We report two patients with babesiosis and hemolysis treated by apheresis and antibiotics. One case had traditional indications for red blood cell (RBC) exchange, and a second patient was treated with RBC exchange, and plasmapheresis for hemolysis, probably secondary to Babesia parasitemia. Case 1 involved a 44-year-old man with chronic relapsing pancreatitis who had become infected with Babesia from a unit of RBCs transfused during surgery. At 5 weeks after surgery, fever and severe hemolysis developed, along with a hemoglobin of 69 g/L; 30% of his RBCs were found to be infected with Babesia. This patient had several postoperative complications; the babesiosis was treated with clindamycin, quinine, and three RBC exchanges. Parasitemia fell to less then 1% of RBCs, but the patient died of pancreatitis. Case 2 was a 47-year-old man with a renal transplant who had been receiving immunosuppressive therapy for 8 years. He had a history of tick bites, fever, and hemolytic anemia. Analysis of a peripheral blood smear detected Babesia. He was initially treated with antibiotic therapy and two RBC exchanges. Hemolysis improved transiently but worsening parasitemia developed later, as well as an IgG RBC autoantibody. He was then treated by plasmapheresis and RBC exchange. Although his condition improved, he had a third hemolytic episode, which was treated with plasmapheresis and RBC exchange before the parasitemia and autoimmune hemolytic anemia disappeared. In conclusion, immunosuppressed or severely ill people who become infected with Babesia may benefit from RBC exchange or plasmapheresis, or both.

Adult↗
PubMed1998

Clinical neurochemistry: developments in dementia research based on brain bank material.

Brain tissue obtained at autopsy continues to provide unique opportunities in current dementia research. Not only is tissue analysis still essential for diagnosis, but investigation of neurochemical pathology, at a level of resolution beyond current in vivo imaging, continues to provide new insights into the involvement of neurotransmitter signalling systems. These are relevant to therapy which, with respect to symptoms such as cognitive impairment, psychosis and depression, is currently targeted to specific transmitter (cholinergic, dopaminergic and serotonergic) systems. This paper focuses on dopaminergic, cholinergic and histaminergic parameters in Alzheimer's disease (AD), Dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In the normal striatum the dopamine transporter and D2 receptor exhibit distinct rostral-caudal distributions and D2 binding is affected by genetic polymorphism at the Taq 1A locus. The transporter is reduced in both DLB and PD but not AD, correlating with severity of extrapyramidal dysfunction, and receptor abnormalities are apparent in DLB patients responding adversely to neuroleptics. Striatal nicotine receptors are lost in all 3 disorders, further reduced as a result of neuroleptic medication, and elevated as a result of tobacco use. In the thalamus there are selective reductions in presynaptic cholinergic activity in DLB in the reticular nucleus which relate to symptoms of hallucinations and fluctuating consciousness prevalent in this disorder. In the hippocampus coupling of muscarinic M1 receptors, relevant to response to cholinergic therapy, is impaired in areas most affected by beta-amyloid plaques and intact in less affected areas. Analysis of histamine H2 receptors indicates that, despite presynaptic histamine abnormalities in AD, receptor numbers are normal. Such clinically and therapeutically relevant observations on human brain neurochemistry provide a basis for improving therapeutic strategies and prospects of diagnostic in vivo chemical imaging.

Brain↗
PubMed1998

Advance directives in end-stage renal disease inherently involve family and staff.

Advance directives (ADs) have a pivotal role in the practice of clinical nephrology. The following discussion reviews our own viewpoint, drawing on the present literature and on many case anecdotes from our own practice. The review focuses on (1) the intrinsic value of ADs; (2) the impact of family and staff on clinical outcome in general; (3) family relationships and medical decision-making, especially in the area of ADs; (4) the importance of communication within families and between families and staff, as characterized in "family meetings"; and (5) the power of reconciliation when family members and staff "let go." In the final analysis, ADs present the opportunity for approaching medical decision making in a manner that can lessen the stress of making difficult decisions for the patient and even promote peace of mind for all concerned family and staff.

Advance Care Planning↗
PubMed1998

Breakdowns on the path of chronic illness: opportunities for learning.

An unusual case of calciphylaxis, presenting at the onset of end-stage renal disease and evolving into an extended and arduous hospital stay, is described. The medical approach to this case is addressed briefly, but the main focus of this paper is to describe, in the words of various participants, the events and interactions that occurred and to learn from this description how our management of such cases breaks down. When confronted by difficult circumstances, it is common for us to react emotionally in ways that are automatic and based on our own personal histories and behavior patterns. Such automatic reactions prevent us from seeing and understanding what we really need to know about a given situation and leave us vulnerable to discouragement and internal suffering when clinical events do not go well (A. Nierenberg, personal communication, April 1998). The result is often exasperation with patients and families, as well as emotionally laden interactions that do not forward problem solving. In retrospect, the appearance of such breakdowns is not only predictable in the course of chronic illness, but offers us the opportunity to observe our automatic reactions, to re-evaluate our approach, and to redesign our actions. We have written this review, not to find error or blame, but rather to emphasize that we are learning to view these breakdowns as signals first to step back from our automatic reactions and then to listen and communicate clearly as a means to navigating the best pathway through difficult and discouraging clinical challenges.

Calciphylaxis↗