Extent of recovery in the first 12 months of complex regional pain syndrome type-1: A prospective study.

BACKGROUND: The literature concerning the outcomes of complex regional pain syndrome (CRPS) is contradictory, with some studies suggesting high rates of symptom resolution, whilst others demonstrate that CRPS symptoms can persist and lead to significant disability. The aim of the present study was to carefully document the extent of recovery from each of the signs and symptoms of CRPS. METHODS: A sample of 59 patients with recently onset (<12 weeks) CRPS-1 were followed prospectively for 1 year, during which time they received treatment-as-usual. At baseline, 6 and 12 months, the following were measured: CRPS severity scores (symptoms and signs of CRPS), pain, disability, work status and psychological functioning. RESULTS: Analyses showed that rates of almost all signs and symptoms of CRPS reduced significantly over 1 year. Reductions in symptom severity were clinically relevant and were greatest in the first 6 months and plateaued thereafter. However, at 1 year, nearly 2/3 of patients continued to meet the IASP-Orlando criteria for CRPS and 1/4 met the Budapest research criteria for CRPS. Only 5.4% of patients were symptom-free at 12 months. CONCLUSIONS: Overall the results were less optimistic than several previously conducted prospective studies and suggest that few cases of CRPS resolve completely within 12 months of onset. Improvements were generally greater in the first 6 months, and suggest that it may be worth exploring early interventions to prevent long-term disability in CRPS.

Pharmacokinetics of 'party pill' drug N-benzylpiperazine (BZP) in healthy human participants.

There have been many reports of benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) being used as recreational drugs which have been widely marketed in the form of 'party pills' since the late 1990's. However, there is no information currently available describing the pharmacokinetics of these drugs in humans. Human plasma concentrations of BZP were measured in blood and urine samples taken from healthy adults (n=7) over 24h following a 200mg oral dose of BZP. Plasma concentrations of BZP were found to peak at 262 ng/mL (C(max)) and 75min (T(max)). Plasma concentrations of the major metabolites of BZP, 4-OH BZP and 3-OH BZP, were found to peak at 7 ng/mL (at 60 min) and 13 ng/mL (at 75 min) respectively. The elimination half-life (t(1/2)) for BZP was found to be 5.5h. Clearance (Cl/F) was found to be 99L/h. The results of this study indicate that BZP may be detectable in plasma for up to 30 h following an oral dose. Additionally, several urinary metabolites can be detected.

Zinc and Alzheimer's Disease: An Update.

Zinc is an essential metal in human nutrition. A growing number of observations have implicated zinc in the pathophysiology of Alzheimer's disease (AD). Zinc binds and interacts with both the amyloid-ß peptide (the major component of senile plaques) and its larger parent protein known as amyloid precursor protein. Nevertheless, the pathophysiological position of zinc in AD remains unclear. Recently, much research has been published that supports the involvement of zinc in AD pathophysiology. Consistent reports show cerebral zinc to be elevated in selected regions of AD brain, and is highly concentrated within senile plaques. Quantitative assessment of zinc in plaques estimates the zinc concentration to be enriched to the near millimolar concentration range. Furthermore, zinc is also detected in neurons that are positively identified to contain neurofibrillary tangles. This paper reviews current available data that indicate a role for zinc in AD pathology.

Early intervention for schizophrenic disorders. Implementing optimal treatment strategies in routine clinical services. OTP Collaborative Group.

BACKGROUND: Early detection and intervention in schizophrenic disorders is an important challenge for psychiatry. METHOD: Review of literature on effective biomedical and psychosocial intervention strategies. RESULTS: Comprehensive programmes of drug and psychosocial interventions with adults who show early signs and symptoms of schizophrenic disorders may contribute to a lower incidence and prevalence of major episodes of schizophrenia. These programmes combine early detection of psychotic features by primary care services, with close liaison with mental health professionals. Long-term monitoring of signs of recurrence, with further intervention, appears essential to maintain these benefits. CONCLUSIONS: Field trials demonstrate that effective early treatment strategies can be routinely applied in clinical practice.

The role of general practitioners in mental health care: a survey of needs and problems.

OBJECTIVE: To assess the attitudes of general practitioners to central Auckland mental health service provision, and their perceived role and educational needs for clinical management of patients with mental disorders. METHOD: A postal questionnaire survey of all general practitioners within the Auckland Healthcare (Central Auckland CHE) area. RESULTS: 140 (49%) valid responses were returned from 287 sampled. 94% supported a shared care role with mental health services; 57% considered their role as main case manager to be important. 79% of the general practitioners considered they had insufficient time to manage patients with mental disorders. 69% of respondents reported difficulties receiving information about changes to treatment; 65% were unsure whether patients had a case manager, and 64% reported general difficulties with liaison with the mental health services. Education about a range of mental health issues was sought by three quarters of the group. CONCLUSION: This survey suggested that liaison between general practice and specialist mental health services in central Auckland is poor, but that general practitioners are eager to seek ways to improve the care of people suffering mental disorders.

Early detection and intervention for initial episodes of schizophrenia.

Comprehensive programs of drug and psychosocial interventions with adults who show early signs and symptoms of schizophrenic disorders may contribute to a lower incidence and prevalence of florid episodes of schizophrenia. These programs combine (1) early detection of psychotic features by family practitioners and other primary care providers and (2) close liaison with mental health professionals well trained in psychiatric assessment and treatment strategies effective in reducing the prevalence of established cases of schizophrenia. Long-term monitoring for signs of recurrence of these subthreshold psychotic episodes, with further intervention as needed, appears essential to maintain these benefits.

Cognitive brain potentials and regional cerebral blood flow equivalents during two- and three-sound auditory "oddball tasks".

Ten healthy volunteers were examined with single photon emission tomography and 99mTc-exametazime. They were studied on 2 occasions, during a 2- and a 3-sound auditory discrimination (oddball) task. Twenty healthy volunteers were used as controls, studied once at rest. During the 2-tone task there was a bilateral posterior (occipito-) temporal and medial frontal activation, a left pericentral increase, and posterior cingulate suppression. During the 3-sound task activation was again found in posterior (occipito-) temporal, medial frontal cortex, left pericentral, with a small non-significant reduction in posterior cingulate uptake. Compared with the 2-tone task, there was a trend towards higher activity in left medial frontal, right posterior temporal and posterior cingulate cortex in the 3-sound task. P3b amplitudes were negatively correlated with posterior cingulate tracer uptake during both tasks. Positive correlations with P3b amplitudes were found in various frontal and temporal regions. These results are consistent with more invasive localisation studies of P3b. Posterior cingulate cortex appears to be inhibited during the oddball tasks, the more so, the more restricted the range of stimuli, and the greater the task-related recruitment of neurones (P3b amplitude). As expected from its more frontal distribution, P3a amplitude was positively correlated with anterior cingulate tracer uptake, and negatively correlated with temporal cortical activity.

The expert witness in forensic psychiatry.

Forensic psychiatry operates at the interface of the Justice and Health systems and has been defined as: "That branch of psychiatry which requires special knowledge and training in the law as it relates to the mental state of the offender, or alleged offender" [1]. As a consequence of working in this area, psychiatrists are often called into court to give evidence as "expert witnesses". This article examines some of the professional and legal issues involved in providing expert testimony. Secondly, it aims to outline some practical guidelines for giving evidence in the court-room. The predominant focus is on criminal, rather than civil, proceedings in which the forensic psychiatrist gives expert testimony; however much of the information is also relevant to other psychiatrists and psychologists undertaking this role in the legal arena.

Mental health needs in Auckland: 1982-6. An analysis using the Jarman index.

Sociodemographic variables obtained from 1986 census data were used to calculate the Jarman index (a measure of underprivilege) for census area units of Auckland. The index was found to correlate with psychiatric admission rates for the years 1982-6 suggesting it might have some utility as an indicator of demand for mental health services. However, the highest admission rates were from particular central city areas reflecting the presence of a deinstitutionalised patient population with chronic mental disorder. This group would appear to require independent assessment of their needs and specific allocation of resources. Factor analysis of the census variable scores comprising the Jarman index revealed principal components equatable with poverty, living without adult company and transient residence.

Autoregression models of EEG. Results compared with expectations for a multilinear near-equilibrium biophysical process.

This paper considers the properties of parameters (natural frequencies and damping coefficients) obtained from segment-by-segment autoregression analysis of ECoG of rat. The use of a reference signal as control for parameter estimate errors, and multiple regression analyses indicate that the dependencies among parameters calculated from ECoG in the alert (desynchronised) state are of a form consistent with imposition of time-invariance assumptions (implicit in autoregression) on an inherently non-stationary, multimodal, linear and near-equilibrium "thermal" process.

Gross electrocortical activity as a linear wave phenomenon with variable temporal damping, regulated by ascending catecholamine neurones.

We report critical tests for a theory of electrocortical wave processes, in which telencephalic dendritic potentials reflect the mass action of coupled oscillatory circuits exhibiting complicated and unspecified non-linearities, the whole system being driven by active cell firing. Specific assumptions were: stochastic independence for instantaneous coupling parameters in the system, an individual central tendency to the cycle time for each circuit, and the maintenance of steady state conditions. Application of the central limit theorem to the state transition matrix shows that the gross electrocortical waves should be linear waves, exhibiting a multitude of invariant resonant modes, with the natural frequencies of all the modes being clustered about a smaller number of center values. Ascending brain-stem neurones of at least the dopaminergic and noradrenergic classes should regulate both the power of noise-like signals driving the telencephalic resonant patterns, and the temporal damping of each resonance. We devised tests which involved between hemisphere comparisons of electrocortical spectra, before and after unilateral lesion of transhypothalamic ascending fibres, thus obtaining ratio power changes attributable to post lesion asymmetry of damping and driving, in modes of equivalent left-right center-frequencies. These ratio spectra were curve-fitted to an approximate theoretical expression, and the parameters obtained enabled tests of several specific predictions. Estimates of the center values for resonant mode frequencies, comparison of the relative changes in left/right phase with that expected from the ratio changes in power, and estimates of the surface-to-signal transformation of left and right signals made by a back-calculation, all conform to expectation from the theory, and are consistent across lesion of different types of ascending neurone.

Mental phenomena as changes of state in a finite-state machine.

This paper examines the classical functions of the psyche--cognition, affection and conation--from a phenomenological viewpoint and finds them to be defined each in terms of the other. It is held that this circularity of definition reflects the fundamental unity of conscious experience and, as a consequence, that the search for the biological substrate underlying individual functions too readily degenerates into a morphological and biochemical phrenology. An alternative approach, based on considerations from the field of artificial intelligence, is discussed. This approach provides a description of mental phenomena as changes of state in a finite-state machine, the next state being determined by both previous states and current inputs. This concept is shown to be compatible with the descriptions of conscious experience outlined in the phenomenology of Karl Jaspers. It is suggested that neurobiological investigations should be directed towards defining the processes by which state changes occur and further seeking to define mental pathology as aberrations of these dynamic processes.

Schizophrenia as a disorder of cerebral state transition.

This paper offers a speculative consideration of the schizophrenic process in the light of recent findings concerning the wave nature of electrocortical activity. These findings indicate that changes of brain state can be described in the terminology of finite-state machines, and both the instantaneous states and the state transitions can be specified. It is suggested that the mental phenomena of schizophrenia may be reducible to events (some specific type of instability) which could be observed by appropriate analytic techniques applied to EEG. Present empirical EEG findings in schizophrenics are reviewed in this light, and the role of dopamine blockade in treatment is also considered.

Quantitation of a mass action of dopaminergic neurones regulating temporal damping of linear electrocortical waves.

We have previously proposed that electrocortical waves are linear waves, subject to regulation by mesotelencephalic dopaminergic neurones. As a further means to test this theory, selective unilateral lesions of varying extent were made in the nucleii of origin of the dopaminergic mesotelencephalic tract. Changes in the electrocortical power spectrum were assessed by a repeated measure, between hemispheres comparison of ratio changes in power. With increasing unilateral dopamine cell damage, the animals showed increasing contralateral sensorimotor neglect. Curve fitting the ratio changes in power attributable to lesion, showed that estimates of the power of driving signals and the temporal damping moved in reverse directions with increasing extent of lesion, as expected from the theory. A further test was undertaken, to determine whether equal estimates for a transformation of surface signals were obtained from each side. Equality would not be expected if the equation for relative power were invalid. Left and right equality was found for three grades of unilateral lesion.

Contributions of noradrenergic neurones of the locus coeruleus to the temporal damping of linear electrocortical waves.

The preceeding paper (Wright et al. 1985a) gives evidence that mesotelencephalic dopaminergic neurones regulate gross electrocortical waves with linear properties, by influencing the strength of their driving signals and temporal damping. The present study further generalises the findings to ascending noradrenergic neurones, which have different fields of termination to dopaminergic fibres. It is shown that: Estimates of the major groups of natural frequencies for the telencephalic system obtained from curve-fitting the ratio changes in the power spectrum attributable to unilateral noradrenergic neurone lesion, are again centered about the frequencies of the major cerebral rhythms. Estimates of electrode transfer characteristics, using parameters obtained from curve fitting ratio changes in power, in conjunction with the raw left and right power spectra, are again found to be equal left and right, as required by the theoretical derivation. Changes in relative amplitude of electrocortical waves and their relative phase are significantly in accord with the relationship expected from theory.

Relationship between sensorimotor neglect and the specificity, degree and locus of mesotelencephalic dopaminergic cell loss following 6-hydroxydopamine.

The involvement of cell groups within the dopaminergic mesotelencephalic system in the development of the sensorimotor neglect syndrome was re-evaluated in two ways. Firstly, dopaminergic specificity of the neglect was further established by studying the relationship between nomifensine protection of dopamine cells against 6-hydroxydopamine damage and the degree of neglect which resulted. The sensorimotor neglect syndrome which developed following injection of 6-hydroxydopamine was diminished by concomitant treatment with nomifensine in parallel with the degree of protection afforded the dopaminergic cells. Non-specific damage produced by 6-hydroxydopamine was unaltered by nomifensine. Secondly, the role in sensorimotor neglect of both total cell damage, and damage to regional sub-classes of dopaminergic cells was considered. It was found that the extent of the resulting neglect was correlated with the overall damage to the substantia nigra and ventral tegmental area, rather than to any individual region within this dopaminergic system. There was a threshold, involving destruction of approximately one third of the system, below which no neglect syndrome developed. Certain regions, including the ventral tegmental area (VTA), showed a higher partial correlation with the extent of neglect than other regions. While specific lesioning of the A8 or A10 dopaminergic neurons is probably insufficient to produce a neglect syndrome, damage to these areas potentiates the severity of the neglect produced by nigrostriatal lesions. It appears that the involvement of the individual subclasses of the mesotelencephalic dopaminergic neurons in the neglect syndrome is more widespread than previously thought.

State-changes in the brain viewed as linear steady-states and non-linear transitions between steady-states.

Preceding papers concern a linear theory of electrocortical waves and their regulation by brain-stem neurones, in conditions of steady-state. The present paper reconsiders the theory, and generalizes beyond the effects of the fibre systems so far studied. Relaxation and unification of the assumptions upon which the initial model was based is undertaken. It is shown that the generalised model may render state changes within the brain accessible to systematic description, using the EEG as dependent variable. It is proposed that a multitude of stable states are possible within the brain, each characterised by a set of damping parameters for separate linear resonant modes. Within each stable state, the set of sums of resonant modes characterises a sub-space of the total state-space. Transition between stable regions can occur with either perturbation by external signals, or by internal controls. Tentative consideration is given to the role of plastic changes leading to adaptive learning as an attribute of a system of this type.

Effect of nomifensine on the toxicity of 6-hydroxydopamine for mesotelencephalic dopamine neurons.

The ability of nomifensine to protect the dopaminergic cells of the substantia nigra and ventral tegmental areas against 6-hydroxydopamine-induced destruction was evaluated. Nomifensine at high doses (20 mg/kg, i.p.) protected the cells from the effects of low amounts of 6-hydroxydopamine (2 micrograms) injected intracerebrally. This protective effect was markedly decreased with an increased amount of 6-hydroxydopamine (8 micrograms), or by lower doses of nomifensine (6.7 mg/kg). These doses of nomifensine are higher than those required to protect dopaminergic nerve terminals.

Amplitude and phase relations of electrocortical waves regulated by transhypothalamic dopaminergic neurones: a test for a linear theory.

We have previously proposed that electrocortical activity (EEG) arises as a manifestation of linear waves generated by resonance among telencephalic neurones, and that this activity is controlled in part by ascending neurones from the brain-stem, which regulate the damping of each resonance. The present experiments focus on a specific class of ascending neurones, the mesotelencephalic dopaminergic cells, because these cells are thought to mediate important psychological effects, and are conveniently subject to selective lesion. A critical test of the theory is undertaken, by performing selective unilateral lesion, assessing the changes in the power spectrum of the EEG attributable to lesion, and determining whether the changes in phase of the EEG correspond to that predicted from the changes in power. Results support the theory, although the model order applicable in these experiments in inadequate. The consequences of these findings for automata theory, linear network theory and their application to mammalian brains are briefly discussed.