Delirium: a disorder of consciousness?

Delirium is recognised as a disorder of consciousness, however, no evidence has been previously generated to specifically address this premise. In order to evaluate this established notion, we have attempted to review consciousness, the components of consciousness and the emerging evidence for neuroanatomical correlates and then relate this to the recognized features of delirium. We have established that the level of awareness is modulated by alertness and arousal, focused by attention and has the ability to switch between the personal resonances of the experience to the precision of cognition. We have discussed consciousness's relationship with delirium and how the degree of integration of CNS function is mandatory for realisation of higher order function and this has implications for the conceptualisation and management of delirium. We have explored the understanding of downstream, components of consciousness as not giving rise to the full condition of delirium but as a subsyndromal state. We have argued that there is a need for future diagnostic criteria, such as DSM-V, to operationalize disturbance of consciousness together with non-cognitive manifestations of delirium. Intervention studies in delirium have focussed on drugs that improve memory (cholinesterase inhibitors). If memory is only one element of consciousness then we reason instead on evaluating the determinants of consciousness that may be modifiable, such as awareness. Reinforcement of environmental awareness by managing a patient within a low stimulus or familiar surrounding may therefore offer a therapeutic intervention. Overall there seemed support for, or no evidence against, the belief that delirium is a disorder of consciousness. From Descartes 'I think therefore I am' we can say 'I am aware not therefore delirious I am'.

Transcranial magnetic stimulation for depression and other psychiatric disorders.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible alternative to electroconvulsive therapy for the treatment of selected patients with depression, bipolar affective disorder and schizophrenia. The aim of this study was to evaluate the evidence for the effectiveness of rTMS in mood disorders and schizophrenia. METHODS: Studies were identified using MEDLINE (1966 to January 2000), EMBASE/Excerpta Medica (1980 to January 2000), Biological Abstracts and Index to Scientific and Technical Proceedings. A number of biomedical and TMS related websites were also searched. We estimated the number needed to treat to show beneficial effect of rTMS when compared with the placebo controlled group. RESULTS: Seven controlled trials of rTMS depression were identified. Five of these were suitable for meta-analysis and show a beneficial effect of rTMS compared to placebo, with a number needed to treat of 2-3 with a 95 % confidence interval 1.6 to 4.0, total; 81 patients. A single trial of rTMS has also been performed in mania, which shows a beneficial effect of right hemisphere stimulation when compared with left hemisphere stimulation. A controlled trial in schizophrenia failed to show any benefit of rTMS. DISCUSSION: rTMS has demonstrable beneficial effects in depression. The extent and the duration of the anti-depressant effect of rTMS has yet to be defined. There now needs to be randomized controlled trials to compare rTMS directly with standardized electroconvulsive therapy in order to take this subject forward. With regard to the treatment of other mood disorders and schizophrenia, we are at an early stage in the assessment of further studies that are needed to examine any potential role for rTMS.

Metabolism of prostaglandin glycerol esters and prostaglandin ethanolamides in vitro and in vivo.

Prostaglandin glycerol esters (PG-Gs) and prostaglandin ethanolamides (PG-EAs) are generated by the action of cyclooxygenase-2 on the endocannabinoids 2-arachidonylglycerol (2-AG) and arachidonylethanolamide, respectively. These novel eicosanoids may have unique pharmacological properties and/or serve as latent sources of prostaglandins at sites remote from their tissue of origin. Therefore, we investigated the metabolism of PG-Gs and PG-EAs in vitro and in vivo. PGE(2)-G was rapidly hydrolyzed in rat plasma to generate PGE(2) (t(1/2) = 14 s) but was only slowly metabolized in human plasma (t(1/2) > 10 min). An intermediate extent of metabolism of PGE(2)-G was observed in human whole blood (t(1/2) approximately 7 min). The parent arachidonylglycerol, 2-AG, and the more stable regioisomer, 1-AG, also were much more rapidly metabolized in rat plasma compared with human plasma. PGE(2)-EA was not significantly hydrolyzed in plasma, undergoing slow dehydration/isomerization to PGB(2)-EA. Both PGE(2)-G and PGE(2)-EA were stable in canine, bovine, and human cerebrospinal fluid. Human 15-hydroxyprostaglandin dehydrogenase, the enzyme responsible for the initial step in PG inactivation in vivo, oxidized both PGE(2)-G and PGE(2)-EA less efficiently than the free acid. The sterically hindered glyceryl prostaglandin was the poorest substrate examined in the E series. Minimal 15-hydroxyprostaglandin dehydrogenase oxidation of PGF(2 alpha)-G was observed. PGE(2)-G and PGE(2)-EA pharmacokinetics were assessed in rats. PGE(2)-G was not detected in plasma 5 min following an intravenous dose of 2 mg/kg. However, PGE(2)-EA was detectable up to 2 h following an identical dose, displaying a large apparent volume of distribution and a half-life of over 6 min. The results suggest that endocannabinoid-derived PG-like compounds may be sufficiently stable in humans to exert actions systemically. Furthermore, these results suggest that the rat is not an adequate model for investigating the biological activities of 2-arachidonylglycerol or glyceryl prostaglandins in humans.

Isolation of vascular smooth muscle cells from a single murine aorta.

The vascular smooth muscle cell plays a significant role in many important cardiovascular disorders, and smooth muscle biology is therefore important to cardiovascular research. The mouse is critical to basic cardiovascular research, largely because techniques for genetic manipulation are more fully developed in the mouse than in any other mammalian species. We describe here a technique for isolating smooth muscle cells from a single mouse aorta. This technique is particularly useful when material is limiting, as is frequently the case when genetically modified animals are being characterized.

Quantitative determination of sulfur containing wine odorants at sub-ppb levels. 1. Synthesis of the deuterated analogues.

[2H10]-4-Sulfanyl-4-methylpentan-2-one (d10-SMP), [2H2]-3-sulfanylhexan-1-ol (d2-3SH), and [2H5]-3-sulfanylhexyl acetate (d5-3SHAc), the labeled analogues of impact odorants of wines and other foods, were synthesized to be used for the quantitative determination of the natural compounds in white and red wines by stable isotope dilution assay. The sulfidation was achieved by Michael addition, on mesityl oxide or ethyl hex-2-enoate, respectively, of the sulfhydryl anion generated in situ from triphenylsilanethiol and potassium fluoride under phase transfer conditions. The labeling of 4-sulfanyl-4-methylpentan-2-one (SMP) was obtained from the commercial starting material, [2H6]acetone, so that this method could be used to synthesize 13C-labeled SMP from 13C-labeled acetone. The labeling of 3-sulfanylhexan-1-ol (3SH) and 3-sulfanylhexyl acetate (3SHAc) was obtained from reduction with lithium aluminum deuteride of the Michael adduct ethyl 3-sulfanylhexanoate and [2H3]-acetylation. During the synthesis, 3SH and 3SHAc were partially oxidized to their disulfide, which were reduced back to the thiols by an additional reduction step; the tertiary thiol SMP was less sensitive to this oxidation.

Relationship between vertical ground reaction force and speed during walking, slow jogging, and running.

OBJECTIVE: To obtain descriptive information between vertical ground reaction force (GRF)-time histories and gait speed, running style, and gender. DESIGN: GRF-time history measurements were obtained from male and female subjects during walking, slow jogging, jogging and running on an indoor platform. BACKGROUND: Previous studies have established GRF descriptor variables for male subjects running at speeds from 3 to 6 m s(-1), but very little descriptive data exists for slower or faster running, nor have previous studies reported GRF descriptors separately for female subjects. METHODS: GRF-time histories were recorded for 13 male and 10 female recreational athletes during walking and slow jogging at speeds between 1.5 and 3.0 m s(-1), and running at speeds between 3.5 and 6.0 m s(-1). Vertical GRF-time data for trials with speeds within 0.2 m s(-1) of the prescribed speed were analysed to determine thrust maximum GRF (F(z)) and loading rate (G(z)). RESULTS: In both male and female subjects, F(z) increased linearly during walking and running from 1.2 BW to approximately 2.5 BW at 6.0 m s(-1), remaining constant during forward lean sprinting at higher speeds. F(z) was linearly correlated to G(z), the latter ranging from 8 to 30 BW s(-1) over this speed range. Slow jogging was associated with a > 50% higher F(z) and G(z) in comparison to walking or fast running. CONCLUSIONS: Similar GRF descriptor data and velocity relationships were obtained for male and female subjects. Impact forces were greatest when the subjects adopted a higher, less fixed centre of gravity during slow jogging. RELEVANCE: These results suggest that vertical GRF norms can be established for male and female subjects alike, and that slow or fast running with a lower, fixed centre of gravity decreases impact forces.

Range-gated pulsed Doppler ultrasonographic evaluation of carotid arterial blood flow in small preterm infants with patent ductus arteriosus.

Range-gated pulsed Doppler (RGPD) ultrasonography was utilized to study the effect of a patent ductus arteriosus (PDA) on carotid arterial blood flow in small preterm infants. Carotid arterial flow velocity studies were performed on 23 preterm infants, sampling right and left carotid arteries. Studies on seven infants after PDA ligation and on seven who developed no evidence of PDA were used as controls. A strong relationship was demonstrated between diastolic reversal in the carotid arteries and PDA. The results of this study indicate that the RGPD flow velocity curve from the carotid artery is more sensitive than M-mode echocardiography or clinical examination in detecting PDA, and that PDA in small preterm infants is associated with a distinct abnormality in the carotid arterial flow pattern.

Referral-outreach program links community clinics and hospital.

In the San Diego area, a special program has established a linkage system between a major medical center and community clinics that provide primary care to persons in generally low-income, medically underserved neighborhoods. This system ensures continuity of care for the clinic patients through referrals to the medical center and follow-up back at the clinics and through provision of special services by the medical center's physicians onsite at the clinics.