bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiation between Alzheimer's disease and multi‐infarct dementia: Spect vs MR imaging
Authors: Butler Robert E. , Costa Durval C. , Greco Alina , Ell Peter J. , Katona Cornelius L. E.
Published: December 2004

Single photon emission computed tomography (SPECT) and magnetic resonance (MR) imaging data were obtained in 11 patients with dementia of the Alzheimer type (DAT), 11 with multi‐infarct dementia (MID) and nine elderly, healthy controls. All patients with dementia tolerated a 15‐minute SPECT scan while six patients (27%) did not tolerate the MR examination due to the long acquisition times and/or claustrophobia. Blind qualitative rating of SPECT scans differentiated correctly between dementia and controls in 90% of cases (p < 0.0001; positive predicted value of 91%) and between clinically defined DAT and MID in 77% of cases (p < 0.01; positive predicted value of 80%). It correctly identified clinical group membership (control, DAT or MID) in 71% of cases (p <0.001; predicted positive value of 94%) but failed to differentiate between DAT and MID (positive predicted value of 50%). Overall, MR imaging correctly identified clinical group membership in 61% of cases (p < 0.01). Semiquantitative SPECT data demonstrated reduced regional cerebral blood flow (rCBF) in all regions of interest (ROI) except right frontal and right anterior parietal in both DAT and MID compared with controls (p < 0.05). There was no statistically significant difference between DAT and MID subjects in rCBF in any ROI. Several correlations between rCBF and cognitive variables were found in the MID but not the DAT group. Though the sample in this study is small, our findings suggest that Tc‐99m HMPAO SPECT is a useful and practical tool in the assessment of patients with dementia. It enables the differential diagnosis of dementia and by using semiquantitative data it helps to establish the severity of disease.
An audit of the use of chest radiography in the elderly mentally ill
Authors: Brown Martin
Published: December 2004

Chest X‐rays are widely used in the investigation of patients with both functional and organic mental illness. For patients with dementia their routine use has been recommended by many authorities. However, the existing evidence to support such use is not strong. A prospective audit was performed to ascertain the yield of chest X‐rays affecting patient management in a series of consecutive admissions covering all diagnoses. The yield of unexpected findings was substantial, but few of these led to a change in medical management and hence potentially to the course of illness. Apparently significant radiological findings did not always correlate with actual physical illness. The low yield of results affecting management does not support the routine use of chest radiography in elderly mentally ill, and its use should be limited to when functional illness is refractory to treatment or when demented patients suddenly deteriorate without obvious cause.
Capacity assessments for requests to restore legal competence
Authors: Silberfeld Michel , Corber Wendy , Madigan Kevin V. , Checkland David
Published: December 2004

We argue that acceptance of competence as decision‐specific, together with a resultant likely increase in limited guardianship orders, will lead to an increase in requests for restoration of legal competence by those under such orders. Six central issues facing the assessor of capacity/competence in the restoration of legal competence are discussed. Suggestions are made as to how these issues can be addressed in forming a clinical judgement. The profile of 17 cases where there was a request to restore legal competence is reviewed.
Antidepressants and the elderly: Double‐blind trials 1987‐1992
Authors: Anstey Kaarin , Brodaty Henry
Published: December 2004

We reviewed all double‐blind antidepressant trials reported between 1987 and 1992 in samples of people aged 55 years or more with a primary diagnosis of major or clinical depression. There was an increase in the annual rate of trials conducted compared with the period from 1964 to 1986. About 27% of patients commencing trials withdrew prior to completion. Of those who completed, there was a general reduction of about 55% in scores on the Hamilton Rating Scale for Depression. No differences in efficacy between drugs were found. Newer antidepressants, particularly selective serotonin reuptake inhibitors, appeared to have fewer side‐effects, but methodological shortcomings limited interpretation of the results. Recommendations for future research are proposed.
The contribution of hypercortisolaemia to the cognitive decline of geriatric depression
Authors: Mitchell Alexander J.
Published: December 2004

Cognitive impairment in depression is well recognized but poorly understood. A subset of depressed patients exhibit a syndrome of severe neuropsychological deficits which may be partially reversible upon episode resolution. This has been called depressive pseudodementia, the dementia syndrome of depression and depression induced cognitive impairment. The epidemiology, clinical features, natural history and prognosis of this condition support the notion of an underlying organic aetiology. The most plausible neurobiological candidate involved in the pathogenesis is hyperactivity of the hypothalamo‐pituitary‐adrenal (HPA) axis. The homeostatic regulation of the HPA axis becomes increasingly vulnerable to disruption in geriatric depression and perhaps particularly in depressive dementia. Hypercortisolaemia has been correlated with cognitive impairment in depression as well as in other related psychiatric conditions. The mechanism of this abnormality may involve hippocampal dysfunction. Further longitudinal studies are needed to clarify the role of the HPA axis in the cognitive decline of depressive illness.
Clinical and psychosocial variables associated with different types of behaviour problem in new nursing home admissions
Authors: Morriss Richard K. , Rovner Barry W. , German Pearl S.
Published: December 2004

The behaviour problems of 451 subjects at 2 weeks after admission to eight nursing homes were recorded on the Psychogeriatric Dependency Rating Scale. Factor analysis extracted four types of behaviour problem: antisocial behaviour, motor activity, communication problems and demands. Associations between the four types of behaviour problems and demographic, psychiatric, psychosocial and physical variables were examined. Multiple linear regression revealed that the four behaviour problem factors were associated with different clinical variables and possibly different aetiologies. However, only 20% or less of the variance in behaviour problems could be explained by variables examined in the study.
Partnership nursing home care for dementia: The glasgow experience—the first 12 weeks
Authors: Lyons Donald , Cohen Mark , Henderson Tom , Walker Nick
Published: December 2004

The outcome of the transfer of 60 elderly patients suffering from dementia from hospital to nursing home care under a partnership contract was studied at 6 and 12 weeks following transfer. Compared with patients remaining in hospital, there was no significant difference in mortality but the nursing home patients exhibited a greater decline in functional ability and a significant excess of pressure sores. Careful planning is required to ensure that such patients do not suffer as a result of transference of care.
The relationship between cognitive function and agitation in senior day care participants
Authors: Cohen‐Mansfield Jiska , Culpepper William J. , Werner Perla
Published: December 2004

The relationship between cognitive impairment and functional status with agitation was assessed in 200 participants of senior day care programs. Results revealed better than 85% agreement in measures of cognitive impairment (BCRS, MMSE, physician assessment of dementia). Regression analyses showed that physically non‐aggressive and verbally aggressive behaviors were related to level of cognitive impairment (BCRS, MMSE). These results showed that physically non‐aggressive behaviors were manifested at earlier stages of dementia than physically aggressive behaviors, which were not manifested until late stages of dementia. Verbally non‐aggressive behaviors increased with severity of dementia up to moderate‐severe levels of impairment and then diminished. In contrast, verbally aggressive behaviors tended to be manifested fairly consistently across levels of dementia with a small increase at the severest levels. Findings are discussed in relation to previous findings for nursing home residents.
Age and compulsory admission
Authors: Srikumar Siva , Orrell Martin W.
Published: December 2004

Compulsory admission is not just restricted to younger psychiatric patients. However, despite the differences in clinical presentation between younger and older adults, there has been very little research comparing different age groups. In this study, elderly and younger adult patients who had compulsory psychiatric admissions were compared according to a number of social and clinical variables. Elderly patients were less likely to have police involvement in an admission but more likely to be referred by their own GP and to live alone. The particular needs of the elderly could be reflected by better guidelines on the use of the Mental Health Act.
Convergent validity of measures of PTSD in an elderly population of former prisoners of war
Authors: Neal Leigh A. , Hill Nicholas , Hughes Julian , Middleton Aisla , Busuttil Walter
Published: December 2004

Thirty former World War II Far East prisoners of war were assessed with a structured clinical interview for PTSD based on DSM‐III‐R criteria and the results compared with the self‐report measures. Thirty per cent of the subjects fulfilled a DSM‐III‐R diagnosis of PTSD and 90% complained of at least one post traumatic intrusive or avoidant symptom. The Mississippi scale was the most accurate measure of PTSD severity (r = 0.81) and the MMPI‐PTSD subscale was the most efficient dichotomous measure of PTSD (sensitivity = 0.89 and specificity = 0.62). The avoidance subscale of the impact of event scale did not discriminate avoidant symptoms from those of intrusion. Self‐report scales for chronic PTSD used in the elderly should be interpreted with caution and require further evaluation of their validity.
Psychotic symptoms in patients with dementia
Authors: Ballard Clive , Oyebode Femi
Published: December 2004

The current article reviews the current state of knowledge pertaining to psychotic symptoms in patients with dementia, drawing on over 70 studies in this area. The majority of studies utilizing a purpose‐designed structured instrument have found a prevalence of psychotic symptoms in excess of 60%. The annual incidence and resolution rates are, however, considerably lower, in the region of 2%. There is little consensus about which factors are of aetiological importance, although it does seem that those with a dementia of moderate severity have the highest prevalence. Perhaps the lack of clarity in this aetiological research partly relates to the limited attention paid to phenomenology. Some suggestions about future research directions which might improve our phenomenological understanding of these conditions are made. Psychotic symptoms are associated with considerable secondary morbidity, including increased aggression, irritability and distress.
Attitudes of health care professionals towards care of the elderly
Authors: Saarela Tuula , Viukari Matti
Published: December 2004

The effect of a short psychogeriatrics training course for primary health care physicians, nurses and social workers on their attitudes towards care of the elderly was explored using the Snape Attitude Scale before and after the training. Participants' attitudes were not altered significantly. The most positive attitudes were found in a reference group formed by nurses specializing in psychiatry. The groups regarded physicians as having the least interest in geriatric care while social workers were felt to have the greatest willingness to care for the elderly.
Frontal lobe syndrome following herpes zoster
Authors: Tarbuck Andrew F. , Malhi Gurjhinder , Dening Thomas R.
Published: December 2004

The case of a 74‐year‐old woman who developed severe behavioural disturbance as part of a frontal lobe syndrome following herpes zoster is described. It is suggested that the frontal lobe deficits developed as a consequence of vascular complications of the infection.
The taps project. 21: Functional and organic comorbidity and the effect of cognitive and behavioural disability on the placement of elderly psychiatric inpatients—a whole‐hospital survey
Authors: Anderson Jeremy , Trieman Noam
Published: December 2004

This article reports a survey by the Team for the Assessment of Psychiatric Services (TAPS)

TheTeam for the assessment of Psychiatric Services (TAPS) is a research team established in 1985 to study the proposed closures of Friern and Claybury Hospitals in North London.

of all inpatients aged 70 years or more resident in Claybury Hospital, London, for more than 12 months. Age, sex, total length of inpatient stay and type of care received were recorded for each subject, and assessments using the Mini‐Mental State Examination (MMSE) and Modified Crighton Royal Behavioural Rating Scale (MCRBRS) were performed. Of 189 inpatients who completed the assessments, 142 (75%) showed unequivocal, severe cognitive disability (MMSE ≤ 17). Patients were assigned to ‘functional’, ‘organic’ or ‘mixed’ diagnosis groups by staff report and case note review. A staff report of ‘mixed’ diagnosis missed a large number of patients who had an original diagnosis of functional psychiatric disorder plus severe measured cognitive disability. Sixty‐five per cent of patients with an original diagnosis of functional psychiatric disorder fell into this category. AFter controlling for age, sex and total length of inpatient stay, patients with a severe degree of reported behavioural problems (MCRBRS ≥ 17) were almost 23 times (95% CI 6.6–79.4) more likely to receive specialized psychogeriatric care than other patients. Severe cognitive disability was not associated with type of care received. Issues related to measurement of cognitive disability across disparate diagnostic groups are discussed.
Use of the mini‐mental state examination to determine the usefulness of subsequent cognitive assessment in moderately to severely demented subjects
Authors: Pearsall Tonya S. , O'neill Desmond , Wilcock Gordon K.
Published: December 2004

This study was undertaken to investigate whether it was possible to identify a ‘cutoff’ score on the Mini‐Mental State Examination (MMSE) below which further cognitive assessment would be of little benefit for research or diagnostic purposes. Evaluation of cognitive assessments in 467 subjects, aged 31–92 (mean 71.4 years), in whom an MMSE score was also available revealed, for those patients scoring ≤5 out of 30, that the majority of a further battery of tasks testing amnesia, aphasia, visuospatial ability and intellectual processing were too difficult. Half of the subjects were too severely impaired to complete 16 of the 17 tasks. When the MMSE score was 8 out of 30 or less, there were eight tasks where a minimum of 50% of patients were untestable. In summary, subjects scoring 8 or less on the MMSE are unlikely to be able to cooperate meaningfully with further cognitive assessment, using psychometric test batteries such as that currently in use in our clinic, and similar batteries.
Pregnancy delusions in elderly depressed women: A clinical feature of Cotard's syndrome?
Authors: Camus Vincent , Schmitt Laurent , Foulon Christine , Lima C. A. DeMendonça , Wertheimer J.
Published: December 2004

Five cases of delusions of pregnancy occuring in women over the age of 64 who had major depressive episodes with mood‐congruent delusions are presented. The relation of such delusions to Cotard's syndrome is discussed.
Functional MRI mapping of stimulus rate effects across visual processing stages
Authors: Schneider Walter , Casey B. J. , Noll Douglas
Published: December 2004

Functional magnetic resonance imaging (fMRI) was used to record cortical activation across multiple stages in the visual system during single character visual search and reversing checkerboard stimulation. Scanning used T2‐weighted, gradient echo sequences with late echo times (TE = 36 ms) with a voxel size of 0.94 * 1.88 mm in‐plane resolution, 4–5 mm deep, on a conventional scanner. A scout experiment recorded six slices to identify major regions of activation. Two slices were selected for extensive assessment. Character stimuli activated small (average 16 mm2), reliable, statistically defined regions of activation in the calcarine fissure, superior occipital cortex, and fusiform‐lingual gyrus. The results include: (1) for character search, the MRI signal change increased linearly from 2.1 to 3.1% for stimulation from 1 to 8 Hz; (2) the character rate effect was equivalent across three levels of the visual system; (3) the checkerboard stimuli showed broader, more intense primary visual activation and less intense secondary visual activation than did character search. Issues relating to fMRI signal variability across the imagining plane, statistical data analysis, signal sensitivity, statistical power, fMRI experimental protocols, and comparisons with positron emission tomography (PET) data are discussed. © 1994 Wiley‐Liss, Inc.
Regional brain activity when selecting a response despite interference: An H215O PET study of the stroop and an emotional stroop
Authors: George M. S. , Ketter T. A. , Parekh P. I. , Rosinsky N. , Ring H. , Casey B. J. , Trimble M. R. , Horwitz B. , Herscovitch P. , Post R. M.
Published: December 2004

The Stroop interference test requires a person to respond to specific elements of a stimulus while suppressing a competing response. Previous positron emission tomography (PET) work has shown increased activity in the right anterior cingulate gyrus during the Stroop test. It is unclear, however, whether the anterior cingulate participates more in the attentional rather than the response selection aspects of the task or whether different interference stimuli might activate different brain regions. We sought to determine (1) whether the Stroop interference task causes increased activation in the right anterior cingulate as previously reported, (2) whether this activation varied as a function of response time, (3) what brain regions were functionally linked to the cingulate during performance of the Stroop, and (4) whether a modified Stroop task involving emotionally distracting words would activate the cingulate and other limbic and paralimbic regions. Twenty‐one healthy volunteers were scanned with H215O PET while they performed the Stroop interference test (standard Stroop), a modified Stroop task using distracting words with sad emotional content (sad Stroop), and a control task of naming colors. These were presented in a manner designed to maximize the response selection aspects of the task. Images were stereotactically normalized and analyzed using statistical parametric mapping (SPM). Predictably, subjects were significantly slower during the standard Stroop than the sad Stroop or the control task. The left mideingulate region robustly activated during the standard Stroop compared to the control task. The sad Stroop activated this same region, but to a less significant degree. Correlational regional network analysis revealed an inverse relationship between activation in the left mideingulate and the left insula and temporal lobe. Additionally, activity in different regions of the cingulate gyrus correlated with performance speed during the standard Stroop. These results suggest that the left midcingulate is likely to be part of a neural network activated when one attempts to override a competing verbal response. Finally, the left midcingulate region appears to be functionally coupled to the left insula, temporal, and frontal cortex during cognitive interference tasks involving language. These results underscore the important role of the cingulate gyrus in selecting appropriate and suppressing inappropriate verbal responses. © 1994 Wiley‐Liss, Inc.
Functional imaging of procedural motor learning: Relating cerebral blood flow with individual subject performance
Authors: Grafton Scot. T. , Woods Roger P. , Tyszka Mike
Published: December 2004

Changes of local synaptic activity during acquisition of a visuomotor skill were examined with positron emission tomography (PET) imaging of regional cerebral blood flow (rCBF). Eight subject learned the pursuit rotor task, a predictable tracking task, during three sequential PET scans (day 1). Subjects returned 2 days later and repeated the three pursuit trials and PET scans (day 2) after completing an extensive practice session. Control scans without movement bracketed the pursuit trials on both days to rule out time effects unrelated to motor skill learning. PET images were transformed to a common stereotaxic space using matched magnetic resonance imaging (MRI) scans. Group learning effects were determined by a repeated measures multivariate analysis of variance (ANOVA). During motor skill acquisition (day 1), increases of synaptic activity were identified in cortical motor areas and cerebellum, supporting the hypothesis that procedural motor learning occurs in motor execution areas. During long‐term practice (day 2), changes were limited to the bilateral putamen, bilateral parietal cortex, and left premotor cortex. To characterize differences in the rate of learning between subjects, each subject's performance data from day 1 was fit with a power function. The exponents were correlated with rCBF data on a pixel‐by‐pixel basis. Rapid skill acquisition was associated with increasing rCBF in premotor, prefrontal, and cingulate areas, and decreasing rCBF in visual processing areas located in the temporal and occipital cortex. This pattern in fast learners may reflect a more rapid shift from a visually guided strategy (accessing perceptual areas) to an internally generated model (accessing premotor and prefrontal areas). © 1994 Wiley‐Liss, Inc.
‘Threats’ to and hopes for estimating benefits
Authors: Ryan Mandy , Amaya‐Amaya Mabelle
Published: December 2004

In a recent paper in this journal, Andrew Lloyd reviewed some potential threats to the estimation of health care benefits in monetary terms. Particular emphasis was placed on the extent to which the use of non‐compensatory heuristics may distort the results. Although it is useful to be reminded of these problems, Lloyd's paper does not do justice to the attention such issues have already received, and continue to receive, within Health Economics. The aim of this paper is twofold. Firstly, it seeks to provide a more balanced and comprehensive view of the evidence by considering some of the methodological work that health economists have conducted in many of the areas pointed out by Lloyd. Secondly, and more importantly, it suggests ways to combine the economic and psychological views of human decision‐making, providing a much more positive perspective to all those researchers out there who recognize the necessity of using stated preference methods to inform health policy. Copyright © 2004 John Wiley & Sons, Ltd.
Über die Acetylierung von primären aromatischen Aminen in vivo und in vitro. Versuche mit p‐Aminobenzoesäure, 2‐Sulfanilamido‐thiazol, Anilinhydrochlorid und Sulfanilsäure
Authors: Zehender F.
Published: December 2004

Von einer Reihe primärer aromatischer Amine wurde der Acetylierungsgrad einerseits beim Menschen und beim Meerschweinchen, andererseits in vitro unter Verwendung von Essigsäure‐anhydrid bestimmt. Für drei von den vier untersuchten Verbindungen, für p‐Aminobenzoesäure, Sulfathiazol und Sulfanilsäure gilt folgende Gesetzmässigkeit: Einer Substanz mit grösserer Basizitätskonstante entspricht eine stärkere Acetylierung in vivo und in vitro. Anilin macht im Tierversuch eine Ausnahme, indem es relativ wenig acetyliert wird.
Synthese von optisch aktiven, natürlichen Carotinoiden und strukturell verwandten Verbindungen. III. Synthese von (+)‐Abscisinsäure, (−)‐Xanthoxin, (−)‐Loliolid, (−)‐Actinidiolid und (−)‐Dihydroactinidiolid
Authors: Kienzle Frnak , Mayer Hans , Minder Rudolf E. , Thommen Hans
Published: December 2004

Synthesis of optically active natural carotenoids and structurally related compounds. III. Synthesis of (+)‐abscisic acid, (−)‐xanthoxin, (−)‐loliolide, (−)‐actinidiolide, and (−)‐dihydroactinidiolide

The syntheses of (+)‐abscisic acid (1), (−)‐xanthoxin (2), (−)‐loliolide (3), (−)‐actinidiolide (4), and of (−)‐dihydroactinidiolide (5) from one common starting material are reported. The syntheses yield also some enantiomeric or diastereomeric analogues.
Photochemische Reaktionen. 97 Mitteilung [1]. Zur Photochemie konjugierter Epoxy‐diene II. Versuche mit (E)‐β‐Jonyliden‐epoxiden
Authors: Alder Alex Peter , Wolf Hans Richard , Jeger Oskar
Published: December 2004

Photolysis of Conjugated Epoxy‐dienes

Direct and sensitized excitation of the (E)‐β‐ionylidene‐epoxides 1 and 4 leads to different types of isomerizations. Thus photocycloelimination to the cyclopropene‐ketones 2 and 6 is only achieved by 1(π, π*)‐excitation (λ=254 nm), whereas 3(π, π*)‐excitation (λ > 280 nm, acetone) gives selective C(1′), O‐cleavage of the oxirane (1→7 – 10 and 4→11 – 13). In contrast to 1 the twofold methylsubstituted epoxy‐diene 4 shows mainly (E/Z)‐isomerization (4 → 5) on both 1(π, π*)‐ and 3(π, π*)‐excitation while the isomerizations 4→6 and 4→11 – 13 are minor processes, only.
Hydrogen Evolution from Water by Visible Light, a Homogeneous Three Component Test System for Redox Catalysis
Authors: Kalyanasundaram Kuppuswamy , Kiwi John , Grätzel Michael
Published: December 2004

Irradiation by visible light of a neutral aqueous solution containing Ru (bipy) as a sensitizer, methylviologen (MV+2) as an electron acceptor and triethanolamine or cysteine as an electron donor leads to the formation of stable methylviologen radical cation (MV+). The kinetics and mechanism of the photoinduced reactions occurring in such a system were explored by laser photolysis technique. In the presence of Adams catalyst MV+ is reoxidized by water under simultaneous evolution of hydrogen. Optimum conditions for the water reduction under continuous illumination are elaborated and implications for an energy conversion system discussed.
Synthese von optisch aktiven, natürlichen Carotinoiden und strukturell verwandten Naturprodukten. VIII. Synthese von (3S,3′S)‐7,8,7′,8′‐Tetradehydroastaxanthin und (3S,3′S)‐7,8‐Didehydroastaxanthin (Asterinsäure)
Authors: Bernhard Kurt , Kienzle Frank , Mayer Hans , Müller Robert K.
Published: December 2004

Synthesis of Optically Active Natural Carotenoids and Structurally Related Compounds. VIII. Synthesis of (3S,3′S)‐7,8,7′,8′‐Tetradehydroastaxanthin and (3S,3′S)‐7,8‐Didehydroastaxanthin (Asterinic Acid)

The synthesis of all‐trans‐(3S,3′S)‐3,3′‐dihydroxy‐7,8, 7′,8′‐tetradehydro‐β, β‐carotene‐4,4′‐dione (1), of all‐trans‐(3S,3′S)‐3,3′‐dihydroxy‐7, 8‐didehydro‐β,β‐carotene‐4,4′‐dione (2) (asterinic acid = mixture of 1 and 2), and of their 9,9′‐di‐cis‐ and 9‐cis‐isomers is reported starting from (4′S)(2E)‐5‐(4′‐hydroxy‐2′, 6′,6′‐trimethyl‐3′‐oxo‐l′‐cyclohexenyl)‐3‐methyl‐2‐penten‐4‐ynal (8). The absolute configuration (3S,3′S) for both components 1 and 2 of asterinic acid ex Asterias rubens is confirmed on the basis of spectroscopic and direct comparison.
Cob(I)alamin als Katalysator. Retention der Konfiguration bei der reduktiv‐protonenübertragenden Spaltung der Co, C‐Bindung eines Alkylcobalamins. 7. Mitteilung [1]
Authors: Fischli Albert , Müller Peter Michael
Published: December 2004

Cob(I)alamin as Catalyst. 7. Communication [1]. Retention of Configuration during the Reductive Cleavage of the Co, C‐Bond of an Alkylcobalamin

Using catalytic amounts of cob(I)alamin (see Scheme 1) in aqueous acetic acid (−)‐α‐pinen (1) and (−)‐β‐pinen (2; s. Scheme 3) have been reduced. A large excess of metallic zinc served as electron source. The saturated products 5–8 (see Scheme 3) and the mechanistic aspects of their generation are discussed. The relative amounts of cis‐ (5) and trans‐pinane (6) lead to the conclusion that the reductive cleavage of the Co, C‐bond accompanied by H+ transfer in an alkylcobalamin occurs with retention of configuration. This result is in agreement with the corresponding cleavage of the Co,C‐bond of an alkyl[hydroxy‐diazaoctahydroporphinato]cobalt complex [9].
Stereoselective total syntheses of (±)‐chanoclavine I and (±)‐isochanoclavine I by an intramolecular nitrone‐olefin/cycloaddition. Preliminary communication
Authors: Oppolzer Wolfgang , Grayson J. Ian
Published: December 2004

The racemic alkaloids chanoclavine I (1) and isochanoclavine I (2) have been synthesized stereoselectively from indole‐4‐carbaldehyde (3) by a sequence of 11 operations in overall yields of 14% and 2.4%, respectively. The key step 6 → 8 (Scheme 2) involves a transient nitrone 7 which undergoes a regio‐ and stereoselective intramolecular cycloaddition to a 1,2‐disubstituted olefinic bond.
A case of triazolam abuse
Authors: Kuniyoshi M. , Arikawa K. , Miura C. , Nakamura J. , Inanaga K.
Published: December 2004

A case of abuse of triazolam, a short‐acting benzodiazepine, was experienced. A 35‐year‐old male, with a tendency to mixed drug dependence with nitrazepam, etc., and a background of neurotic anxiety and insomnia, started self‐administration of triazolam. Application of triazolam was frequent, with large doses up to a maximum of 80 mg/day (320 times the recommended daily dose of 250 micrograms). In addition to psychic dependence, occurrence of withdrawal symptoms confirmed formation of physical dependence, which was also supported by EEG together with the appearance of various autonomic and psychic symptoms.

Even though triazolam is known to be comparatively safe, this case confirms that it can induce physical dependence upon frequent administration of a large amount, together with psychic dependence, and therefore care must be taken with regard to dosage. In particular, self‐administration of the drug should be strictly controlled.
Recent advances in the clinical pharmacology of benzodiazepines part II: Pharmacodynamics
Authors: Saletu B. , Pakesch G.
Published: December 2004

Tranquilizers, and specifically benzodiazepines (BZD), have become one of the most widely used group of drugs in the world; some have suggested too widely used. Interest in these drugs in still extremely high, both from the scientific and sociological point of view. This is best documented by the fact that the present review is based on more than 700 articles published between 1981 and 1984 covering various aspects of clinical pharmacology. Pharmacodynamic studies are mostly concerned with effects of the drug on the central nervous system (CNS), as well as on behavious and neuroendocrine functions. The former include computer‐assisted quantitative analyses of the scalp‐recorded wake electroencephalogram (EEG), based on which it seems possible to determine if, how, when and at what dose a newly developed compound affects the human brain. Sleep investigations are now concerned not only with the effect of the drug on the all‐night sleep, but also on the quality of awakening and early morning behaviour as well as with residual effects during daytime, affecting amnestic and cognitive functions, psychomotor performance (specifically in regard to driving ability), as well as mood and affectivity. Finally, for almost a decade increasing concern has been expressed about the widespread use of tranquillizers in society. Scientific evidence concerning thiss issue will be reviewed so that an appropriate medical decision may be reached for the treatment of the individual patients after consideration of the beneficial effects as well as undesirable side‐effects.
Urinary cyclic AMP response to bovine parathyroid hormone during treatment with neuroleptics
Authors: Waller Derek G. , Albano Janet D. M. , Guyedwards J.
Published: December 2004

The urinary cyclic AMP response to bovine parathyroid hormone and urinary concentrating ability (max Uosm) after des‐amino‐D‐arginine vasopressin were studies in nine volunteers and seven patients receiving long‐term neuroleptic treatment. Max Uosm was lower in the patient group (770 ± 70 mosmol/kg) compared with the controls (948 ± 152 mosmol/kg) but the trend to a lower cAMP response to bovine PTH was not statistically significant. These results suggest that, although adenylate cyclase inhibition may contribute, other mechanisms are also important in the genesis of reduced uring concentrating ability in patients treated with psychotropic drugs.
Response to clomipramine after short course of lithium in treatment‐resistant depression: Does lithium have a ‘priming’ effect?
Authors: Chiu Leo P. W. , Rimon Ranan
Published: December 2004

A patient with a treatment‐resistant depression of 15 months duration is reported. Initially he showed no response to clomipramine 150 mg daily for 1 month. When lithium carbonate 600 mg daily was added for 4 days he developed signs of lithium intoxication: drowsiness, confusion, and dystonia. After lithium was withdrawn the patient improved dramatically. We hypothesize that lithium may potentiate the antidepressant effect of tricyclic antidepressants (TCA) even if it is administered as a short course of treatment.
The renal excretion of xanthurenic acid following L‐tryptophan loading in depressed patients
Authors: Maes M. , De Ruyter M. , Suy E.
Published: December 2004

Xanthurenic acid (XA) is a secondary product of the biosynthesis of nicotinamide from L‐tryptophan. Disturbances in this pathway have been observed in depression. An enhanced glucocorticoid secretion is considered to induce this pathway. This could result in reduced levels of L‐tryptophan (L‐TRP) in the plasma. The present study investigates whether the synthesis of XA from L‐TRP is distrubed in depression, and also whether the synthesis of XA is intercorrelated with L‐TRP or measures of glucocorticoid secretion. To this end the XA excretion in 24 hour urine following L‐TRP loading was determined in 166 psychiatric inpatients. There were no significant differences in XA excretion between non‐depressed psychiatric controls, minor depression and major depression. Among the depressed patients there was a significant (p<0·01) negative correlation between the excretion of XA and total L‐TRP levels in plasma, with abnormally decreased (p<0·0006) L‐TRP levels occurring in the depressed patients with a disturbed XA excretion (≥ 106·8 m̈mol/24 hour).
Neutrophil mobilization in lithium‐induced neutrophilia
Authors: Roath Stuart , Choudhury Dina , Edwards J. Guy , Francis John L. , Gordon Alan
Published: December 2004

Twenty patients on long‐term treatment with lithium who had persistently elevated neutrophil counts were challenged with adrenalin and hydrocortisone to measure their marginal and bone marrow granulocyte pools. Compared with normal controls the results suggest that the absolute numbers of granulocytes in each pool are not increased, although the percentage change is diminished because of the greater baseline values in the experimental group. These data suggest that lithium acts on granulopoiesis within the bone marrow, and are in keeping with the concept that the granulocyte reserve has a finite size. There is no apparent connection between lithium‐induced neutrophilia and either the therapeutic or unwanted effects of lithium.
Intra‐Accumbens trh prolongs maintenance of tolerance to hypothermic effect of ethanol in rats
Authors: Pucilowski O. , Trzaskowska E. , Kostowski W.
Published: December 2004

Tolerance to the hypothermic effect of ethanol (Et–OH) developed in male Wistar rats treated daily with 5 g/kg of 20 per cent ET–OH v/v i.g. for 6 days. On Day 6 Et–OH treatment was discontinued and the animals were divided into two groups injected into the nucleus accumbens septi (NAS), either with pGlu‐His‐Pro‐NH2 (TRH) or saline. The peptide was injected via permanently implanted cannulae in doses of 10 or 30 m̈g in 0.5 m̈l on each side once daily. The effect of such treatment on the maintenance of Et–OH tolerance was assessed by measuring the temperature decrement in response to a challenge dose of Et–OH (5 g/kg i.p.) given on Day 10. It was found that in saline‐treated rats the initial tolerance declined. TRH‐injected groups exhibited constantly low response to hypothermic action of Et–OH. In a control experiment TRH was shown to have no effect on the body temperature after intra‐accumbens application in Et–OH‐naive rats.
Erythrocyte lithium–sodium countertransport and total body lithium pharmacokinetics in patients with affective illness
Authors: Rybakowski Janusz , Lehmann Wenancja , Kanarkowski Roman
Published: December 2004

Previous studies suggested that in patients with affective illness, lithium ion accumulated more in erythrocytes (higher erythrocyte lithium ratio) as well as in the total body (greater lithium retention). The aim of this study was to estimate the relationship between erythrocyte lithium transport mechanisms and the parameters of lithium pharmacokinetics in 11 affective patients during depressive episodes. It was found that the activity of erythrocyte lithium–sodium countertransport (LSC) governing lithium transport out of the erythrocytes, measured in vitro significantly correlated with rate constant (K21) of lithium trnsport from intra‐ to extracellular compartment. Passive lithium diffusion (PLD) in erythrocytes correlated with K21/K12 ratio. Neither LSC nor PLD correlated with renal lithium clearance. The results show that, in affective patients, the activity of erythrocyte LSC may serve as a model of the intensity of lithium extrusion from cells in the total body.
The psychopharmacological effects of single doses of prolonged release formulations of dimethindene and chlorpheniramine in human volunteers
Authors: Lee Anthony , Lader Malcolm , Kitler Mary Ellen
Published: December 2004

1. The effects of single doses of dimethindene (retard) 2·5 mg, chlorpheniramine (TD) 12mg and placebo on a battery of physiological, performance and subjective measures were studied in a double‐blind, crossover study in 12 healthy subjects.

2. Dimethindene had a different EEG profile from chlorpheniramine; while both active drug treatments were associated with an increase in 8·0–13·0 Hz waveband activity, dimethindene alone produced less 2·0–4·0 Hz activity.

3. The two active drugs were associated with an improvement in tapping rate. Dimethindene had no effect on simple reaction time, while chlorpheniramine was associated with a slowing in this measure.

4. Subjective measures generally indicated an improvement in general alertness and contentedness with both dimethindene and chlorpheniramine.

5. It is concluded that single doses of sustained‐release formulations of these antihistamines are slightly stimulant in effect and are useful where sedation in unacceptable.
Evidence that imipramine‐induced postural hypotension may be centrally mediated
Authors: Middleton H. C. , Nutt D. J. , Anastassiades P.
Published: December 2004

The acute effects of imipramine upon cardiovascular reflexes have been studied in normal volunteers. Respiratory sinus arryhthmia, blood pressure and heart rate responses to standing, heart rate response to Valsalva's manoeuvre and the heart rate and blood pressure responses to isometric exercise were measured before and after 100 mg and 40 mg imipramine orally on separate occasions. Neither dose had an appreciable effect upon respiratory sinus arrhythmia (RSA), heart rate response to Valsalva or the responses to isometric exercise.

Imipramine caused dose‐related rises in resting heart rate and blood pressure. In view of the unchanged RSA these cannot be attributed to vagal blockade and may reflect peripheral noradrenaline reuptake inhibition. Imipramine profoundly altered the heart rate response to standing in a dose‐related manner. This suggests an impairment of the orthostatic reflex. The presence of normal responses to the Valsalva manoeuvre and isometric exercise suggests that peripheral mechanisms were intact, and it is therefore likely that impairment of the orthostatic reflex is due to the effect of imipramine upon central monoaminergic neurones normally involved in this response.
The pharmacodynamic influence of three benzodiazepines on rapid eye movements, K‐complexes and sleep spindles in healthy volunteers
Authors: Kubicki St. , Haag‐Wüsthof C. , Röhmel J. , Herrmann W. M. , Scheuler W.
Published: December 2004

‘Equipotent’ doses of lormetazepam, triazolam and flunitrazepam were studied for their effect on K‐complexes, sleep spindles and rapid eye movements (REM). Receptor affinity was used as the criterion for equipotency. This showed that triazolam, lormetazepam and flunitrazepam display a ratio to each other of 1:2:4. However, it was found that lormetazepam caused only slight changes in the three neurophysiological parameters despite being given at twice the dose considered to be equipotent. In contrast, triazolam and flunitrazepam produced a great reduction in the number of K‐complexes, a marked increase in sleep spindles and a substantial reduction of REM activity; both substances suppressed the first REM period, and flunitrazepam even suppressed the second in some cases. The influence of all three benzodiazepines on the dissociation of K‐complexes and sleep spindles is, however, equal; epochs with either K‐complexes or sleep spindles are favoured compared to epochs with both K‐complexes and sleep spindles. The general reduction in the number of K‐complexes and increase in sleep spindles can be interpreted as a sleep‐protective effect. However, the parameter for dose‐finding should be REM suppression, since this has the most profound adverse effect on the cyclical structure of sleep—now considered to be the most reliable indicator of a balanced sleep pattern.
A double‐blind dose‐finding study of rolipram in patients with major depressive disorder
Authors: Bennie E. H. , Chakravarti S. K. , Jarman C. M. B. , Khan K. , Master D. , Murray G. H. , Meya U. , Soni S. D. , Shaw S. H. , White A. C.
Published: December 2004

Rolipram improves signal transmission in central noradrenergic neurones with a novel mechanism of action: enhanced noradrenaline (first messenger) synthesis and release, and inhibition of cAMP (second messenger) breakdown. Several comparative trials to prove antidepressant activity are under way. Results of a multicentre double‐blind trial with three different dosages of rolipram involving 98 patients will be presented. Reponse rates in all dosages were similar and comparable to those reported in the literature on tricyclic antidepressants. In addition rolipram was tolerated well. A significant relationship between dosages and effects, however, could not be established.
A serotonin hypothesis of panic disorder
Authors: Kahn Rene S. , Van Praag Herman M.
Published: December 2004

Despite numerous animal studies indicating an important role of serotonin (5‐HT) in anxiety, 5‐HT's function in the regulation of human anxiety has hardly been studied. Recent clinical studies suggest an involvement of 5‐HT systems in panic disorder. This paper will briefly review the pertinent data on 5‐HT and panic disorder and propose a specific hypothesis on 5‐HT abnormalities in that disorder.
Chronic diazepam treatment: Effect of dose on development of tolerance and incidence of withdrawal in an animal test of anxiety
Authors: Sandra E.
Published: December 2004

The effect of the treatment dose of diazepam was assessed on the rate of development of tolerance to diazepam's effects on rat behaviour in the elevated plus‐maze test of anxiety. Tolerance developed more rapidly when treatment was with the higher dose: after 14 days when rats were given 2·5 mg/kg/day, but not until 21 days when they were given 1 mg/kg/day. When rats were tested undrugged 36 h after the last of 14 daily doses of diazepam (2·5 mg/kg) they showed behavioural changes indicating increased anxiety. Rats tested at this time with a lower dose of diazepam (1 mg/kg) also showed changes indicating increased anxiety compared with the control scores. This indicates that a more gradual tapering of doses would be necessary to avoid withdrawal responses.
Comparison of the effects of fengabine, a novel antidepressant, with those of amitriptyline on psychomotor and autonomic functions in healthy volunteers
Authors: Theofilopoulos N. , Gray C. M. , Szabadi E. , Bradshaw C. M.
Published: December 2004

Two single doses (300 and 600 mg) of fengabine, a novel antidepressant, a single dose (50 mg) of amitriptyline, and a single dose of placebo were taken by sixteen male healthy volunteers (18–30 years), in weekly experimental sessions, according to a balanced double‐blind cross‐over design. In Part A (eight subjects) subjective mood state, psychomotor performance and some baseline autonomic functions were measured before, and 1, 3 and 5 hours after drug taking. In Part B, cholinoceptor‐mediated tissue responses (pilocarpine‐evoked miosis and carbachol‐evoked sweating) were measured two and a half hours after drug taking. Fengabine and placebo did not affect any of the test results, whereas amitriptyline had effects consistent with the sedative (reduction in alertness, impairment of psychomotor performance) and antimuscarinic (reduction in salivation and carbachol‐evoked sweating) properties of the drug.
The effects of lormetazepam on contractile force of the gastrocnemius muscle and on memory of healthy young volunteers
Authors: Deijen J. B. , Heemstra M. L. , Orlebeke J. F. , De Vries J. , Neijzen J. B. M.
Published: December 2004

One group of 10 young subjects were tested twice; in one test session 2 mg lormetazepam, in the other session placebo was administered, in random order. One subject dropped out. In one test session contractile force measurements were made six times; one measurement took place before treatment and the other measurements after treatment with the study medication. Each measurement of contractile force consisted of pushing weights of 0 to 10 kg and exerting maximal force. The corresponding electromyogram (EMG) of the gastrocnemius muscle was recorded. For the forces of 0 to 10 kg the regression was established of EMG on contractile force. Treatment effects on memory were investigated by means of a selection of tests, covering short‐term and long‐term memory, in terms of recall and recognition. Analyses of covariance were performed on the regression coefficients of EMG/ contractile force and on the data of maximally exerted force, the pre‐treatment scores serving as covariate. These analyses did not result in any difference for the two treatment conditions, leading to the conclusion that the administration of lormetazepam did not have any direct action on the contractile systems of human muscle. The t‐tests performed on the memory data resulted in a significant impairment of performance on the long‐term memory tasks, whereas short‐term memory was not impaired. It is concluded that, in accordance with previous research, the administration of lormetazepam results in an impairment in the acquisition of new information in long‐term memory, but also in impaired retention.
Cannabis and human social behaviour
Authors: Marks David F. , Pow Gillian M.
Published: December 2004

Although an illicit substance, cannabis is a commonly used recreational drug. In spite of its social usage, relatively little scientific research has been directed towards the question of its social effects and motivations for use. In this experiment five doses of cannabis up to a maximum of 14 mg Δ‐9‐THC were administered double‐blind and in a balanced order. Self‐ratings of ‘highness’, intoxication, and social effects were obtained and also subjects' ratings of each other's behaviour. Similar ratings were obtained from six independent judges who viewed videotapes. Significant non‐linear dose‐response effects and interactions with acquaintanceship provide further evidence of the importance of setting in determining cannabis effects.