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Philip D. Kanof

Bio: Philip D. Kanof is an academic researcher from Icahn School of Medicine at Mount Sinai. The author has contributed to research in topics: Nucleus basalis & Choline acetyltransferase. The author has an hindex of 18, co-authored 34 publications receiving 2331 citations. Previous affiliations of Philip D. Kanof include Veterans Health Administration & United States Department of Veterans Affairs.

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TL;DR: It is suggested that of all the neurochemical species quantified, the cholinergic indices may be unique in their association with dementia severity, and none of the amines, their metabolites, or the neuropeptides quantified related significantly to dementia severity in the AD cohort.
Abstract: Cholinergic markers, neuropeptides, and amines and their metabolites were sampled from identical specimens across 10 neocortical regions in a large sample of Alzheimer's disease (AD) cases and controls. Levels of choline acetyltransferase, acetylcholinesterase, somatostatin, corticotropin-releasing factor, serotonin, and 5-hydroxyindoleacetic acid were significantly reduced in AD versus controls. After data reduction, the most descriptive neurochemical indices were used to examine the relationship of neurochemical measures and dementia severity within the AD sample, controlling for age effects. Dementia severity ratings were based on antemortem assessments (46.9% of AD sample) and postmortem chart review (53.1% of the AD sample). Choline acetyltransferase activity was highly correlated with clinical dementia ratings across the neocortex of the AD cases. Somatostatin and corticotropin-releasing factor levels were correlated with dementia severity only when control cases were included in the analyses. None of the amines, their metabolites, or the neuropeptides quantified related significantly to dementia severity in the AD cohort. These data (a) confirm the strong association of cholinergic deficits with functional impairment in AD and show that this association is independent of age and (b) suggest that of all the neurochemical species quantified, the cholinergic indices may be unique in their association with dementia severity.

571 citations

Journal ArticleDOI
TL;DR: In this paper, two rating scales for measuring the signs and symptoms of opiate withdrawal are presented: Subjective Opiate Withdrawal Scale (SOWS) contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely).
Abstract: Two new rating scales for measuring the signs and symptoms of opiate withdrawal are presented. The Subjective Opiate Withdrawal Scale (SOWS) contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). The Objective Opiate Withdrawal Scale (OOWS) contains 13 physically observable signs, rated present or absent, based on a timed period of observation of the patient by a rater. Opiate abusers admitted to a detoxification ward had significantly higher scores on the SOWS and OOWS before receiving methadone as compared to after receiving methadone for 2 days. Opiate abusers seeking treatment were challenged either with placebo or with 0.4 mg naloxone. Postchallenge SOWS and OOWS scores were significantly higher than prechallenge scores in the naloxone but not the placebo group. We have demonstrated good interrater reliability for the OOWS and good intrasubject reliability over time for both scales in controls and in patients on a methadone maintenance program. These scales are demonstrated to be valid and reliable indicators of the severity of the opiate withdrawal syndrome over a wide range of common signs and symptoms.

467 citations

01 Jan 1987
TL;DR: Good interrater reliability for the OOWS and good intrasubject reliability over time for both scales are demonstrated to be valid and reliable indicators of the severity of the opiate withdrawal syndrome over a wide range of common signs and symptoms.
Abstract: Two new rating scales for measuring the signs and symptoms of opiate withdrawal are presented. The Subjective Opiate Withdrawal Scale (SOWS) contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). The Objective Opiate Withdrawal Scale (OOWS) contains 13 physically observable signs, rated present or absent, based on a timed period of observation of the patient by a rater. Opiate abusers admitted to a detoxification ward had significantly higher scores on the SOWS and OOWS before receiving methadone as compared to after receiving methadone for 2 days. Opiate abusers seeking treatment were challenged either with placebo or with 0.4 mg naloxone. Postchallenge SOWS and OOWS scores were significantly higher than prechallenge scores in the naloxone but not the placebo group. We have demonstrated good interrater reliability for the OOWS and good intrasubject reliability over time for both scales in controls and in patients on a methadone maintenance program. These scales are demonstrated to be valid and reliable indicators of the severity of the opiate withdrawal syndrome over a wide range of common signs and symptoms.

413 citations

Journal ArticleDOI
TL;DR: The hypothesis that central cholinergic systems are involved in the retention of learned responses in adult rats is supported, and the postacquisition administration of the acetylcholinesterase inhibitor, physostigmine, is suggested to be reversed.

121 citations

Journal ArticleDOI
TL;DR: Results suggest that combined cholinergic/noradrenergic therapy may be of value in the treatment of some Alzheimer's disease patients.

84 citations


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TL;DR: It is shown that emotional reactions to risky situations often diverge from cognitive assessments of those risks, and when such divergence occurs, emotional reactions often drive behavior.
Abstract: Virtually all current theories of choice under risk or uncertainty are cognitive and consequentialist. They assume that people assess the desirability and likelihood of possible outcomes of choice alternatives and integrate this information through some type of expectation-based calculus to arrive at decision. The authors propose an alternative theoretical perspective, the risk-as-feelings hypothesis, that highlights the role of affect experienced at the moment of decision making. Drawing on research from clinical, physiological, and other subfield of psychology, they show that emotional reactions to risky situations often drive behavior. The risk-as-feelings hypothesis is shown to explain a wide range of phenomena that have resisted interpretation in cognitive-consequentialist terms.

4,901 citations

Journal ArticleDOI
TL;DR: It is suggested that dysregulation of locus coeruleus-noradrenergic neurotransmission may contribute to cognitive and/or arousal dysfunction associated with a variety of psychiatric disorders, including attention-deficit hyperactivity disorder, sleep and arousal disorders, as well as certain affective Disorders, including post-traumatic stress disorder.

2,207 citations

Journal ArticleDOI
Paul Harrison1
01 Apr 1999-Brain
TL;DR: Functional imaging data indicate that the pathophysiology of schizophrenia reflects aberrant activity in, and integration of, the components of distributed circuits involving the prefrontal cortex, hippocampus and certain subcortical structures.
Abstract: Despite a hundred years' research, the neuropathology of schizophrenia remains obscure. However, neither can the null hypothesis be sustained--that it is a 'functional' psychosis, a disorder with no structural basis. A number of abnormalities have been identified and confirmed by meta-analysis, including ventricular enlargement and decreased cerebral (cortical and hippocampal) volume. These are characteristic of schizophrenia as a whole, rather than being restricted to a subtype, and are present in first-episode, unmedicated patients. There is considerable evidence for preferential involvement of the temporal lobe and moderate evidence for an alteration in normal cerebral asymmetries. There are several candidates for the histological and molecular correlates of the macroscopic features. The probable proximal explanation for decreased cortical volume is reduced neuropil and neuronal size, rather than a loss of neurons. These morphometric changes are in turn suggestive of alterations in synaptic, dendritic and axonal organization, a view supported by immunocytochemical and ultrastructural findings. Pathology in subcortical structures is not well established, apart from dorsal thalamic nuclei, which are smaller and contain fewer neurons. Other cytoarchitectural features of schizophrenia which are often discussed, notably entorhinal cortex heterotopias and hippocampal neuronal disarray, remain to be confirmed. The phenotype of the affected neuronal and synaptic populations is uncertain. A case can be made for impairment of hippocampal and corticocortical excitatory pathways, but in general the relationship between neurochemical findings (which centre upon dopamine, 5-hydroxytryptamine, glutamate and GABA systems) and the neuropathology of schizophrenia is unclear. Gliosis is not an intrinsic feature; its absence supports, but does not prove, the prevailing hypothesis that schizophrenia is a disorder of prenatal neurodevelopment. The cognitive impairment which frequently accompanies schizophrenia is not due to Alzheimer's disease or any other recognized neurodegenerative disorder. Its basis is unknown. Functional imaging data indicate that the pathophysiology of schizophrenia reflects aberrant activity in, and integration of, the components of distributed circuits involving the prefrontal cortex, hippocampus and certain subcortical structures. It is hypothesized that the neuropathological features represent the anatomical substrate of these functional abnormalities in neural connectivity. Investigation of this proposal is a goal of current neuropathological studies, which must also seek (i) to establish which of the recent histological findings are robust and cardinal, and (ii) to define the relationship of the pathological phenotype with the clinical syndrome, its neurochemistry and its pathogenesis.

1,648 citations

Journal ArticleDOI
22 Mar 2000-JAMA
TL;DR: An important role for Abeta in mediating initial pathogenic events in AD dementia is supported and treatment strategies targeting the formation, accumulation, or cytotoxic effects of Abeta should be pursued.
Abstract: ContextAlzheimer disease (AD) is characterized neuropathologically by the presence of amyloid β-peptide (Aβ)–containing plaques and neurofibrillary tangles composed of abnormal tau protein. Considerable controversy exists as to whether the extent of accumulation of Aβ correlates with dementia and whether Aβ alterations precede or follow changes in tau.ObjectivesTo determine whether accumulation of Aβ correlates with the earliest signs of cognitive deterioration and to define the relationship between Aβ accumulation and early tau changes.Design, Setting, and PatientsPostmortem cross-sectional study of 79 nursing home residents with Clinical Dementia Rating (CDR) scale scores of 0.0 to 5.0 who died between 1986 and 1997, comparing the levels of Aβ variants in the cortices of the subjects with no (CDR score, 0.0 [n = 16]), questionable (CDR score, 0.5 [n = 11]), mild (CDR score, 1.0 [n = 22]), moderate (CDR score, 2.0 [n = 15]), or severe (CDR score, 4.0 or 5.0 [n = 15]) dementia.Main Outcome MeasuresLevels of total Aβ peptides with intact or truncated amino termini and ending in either amino acid 40 (Aβx-40) or 42 (Aβx-42) in 5 neocortical brain regions as well as levels of tau protein undergoing early conformational changes in frontal cortex, as a function of CDR score.ResultsThe levels of both Aβx-40 and Aβx-42 were elevated even in cases classified as having questionable dementia (CDR score = 0.5), and increases of both peptides correlated with progression of dementia. Levels of the more fibril-prone Aβx-42 peptide were higher than those of Aβx-40 in nondemented cases and remained higher throughout progression of disease in all regions examined. Finally, increases in Aβx-40 and Aβx-42 precede significant tau pathology at least in the frontal cortex, an area chosen for examination because of the absence of neuritic changes in the absence of disease.ConclusionsIn this study, levels of total Aβx-40 and Aβx-42 were elevated early in dementia and levels of both peptides were strongly correlated with cognitive decline. Of particular interest, in the frontal cortex, Aβ was elevated before the occurrence of significant tau pathology. These results support an important role for Aβ in mediating initial pathogenic events in AD dementia and suggest that treatment strategies targeting the formation, accumulation, or cytotoxic effects of Aβ should be pursued.

1,308 citations