Emotional activation during therapeutic interaction in traumatic brain injury: effect of apathy, self-awareness and implications for rehabilitation

Apathy and reduced self-awareness are frequent occurring neurobehavioural sequelae following traumatic brain injury (TBI). Apathy, in terms of reduced goal directed activity and lowered motivation, and reduced self-awareness have a negative impact on the rehabilitation process. In this study, 30 patients suffering severe TBI were clinically rated for apathy and monitored for cardiovascular and electrodermal reactivity during baseline, neutral speech and therapeutic interaction. Applying a cut-off score criterion, two thirds of the TBI sample were classified as apathetic. The apathetic patients showed less psychophysiological reactivity from neutral speech to therapeutic interaction, compared to nonapathetic patients. They also reported less perceived emotional discomfort in the therapeutic situation measured with a visual analogue scale. Moreover, reduced self-awareness was associated with low autonomic reactivity. The results suggest that the reduced psychophysiological reactivity in apathetic patients may be a correlate to the lack of emotional responsivity, disengagement, lack of insight and concern about their own situation. Clinically, these results may have implications for psychotherapeutic intervention aimed at improving self-awareness. Recording psychophysiological responses during therapeutic interaction may serve as a method for monitoring emotional involvement during psychotherapy with TBI patients.     

Postoperative pain relief with high-dose epidural buprenorphine: a double-blind study

Forty-five patients scheduled for major abdominal or intrathoracic surgery were assigned at random to two different groups. One group received 0.3 mg and the other 0.9 mg of buprenorphine epidurally to abolish postoperative pain. The first dose was given immediately upon arrival in the ICU, irrespective of pain. Subsequent medication was given on demand. The duration of action and side-effects were recorded. Both doses produced excellent and long-lasting pain relief, but no statistically significant difference was found between the groups, with regard to either the duration of action or the occurrence of side-effects.     

Blood B and T lymphocytes and in vitro cellular immune reactivity in untreated human malignant lymphomas and other malignant tumors.

Peripheral blood lymphocytes and their in vitro reactivity have been recorded prior to treatment in 18 patients with Hodgkins disease, 11 with lymposarcoma, 13 with reticulosarcoma, 20 with various solid tumors and 37 normal control persons. The mean total numbers of lymphocytes, those of T lymphocytes,and the mean reactivity to PHA and ConA were reduced in all groups except lymphosarcoma, although with varying degrees of statistical significance. The percentages of T and B lymphocytes appeared to be normal in all groups, but the ranges of values were somewhat greater than among the normal controls. The mean total numbers of B lymphocytes were normal in all patient groups. All reductions seemed to be more pronounced in patients with disseminated than in those with localized disease, but none of these differences was statistically significant. All patient groups appeared to have reduced reactivity in MLC, while the ability to stimulate control lymphocytes was nearly normal. The results fail to indicate an in vitro immunological abberation specific to Hodgkin's disease. It seems that human malignant, neoplastic diseases are associated with a relatively selective reduction of the total numbers and reactivity of blood T lymphocytes. Various explanations of the reactivity impairment are proposed. The pathogenesis of the reduction of the total number of blood T lymphocytes remains obscure.     

Hydrocortisone and the mitogen-activated protein kinase inhibitor U0126 acutely suppress reactive oxygen species generation from circulating granulocytes after gunshot injuries in the pig

OBJECTIVE: Several external stimuli, including trauma, increase the endogenous production of reactive oxygen species that spontaneously attack vital biological molecules. In addition to their direct toxic effects, several secondary messenger systems are induced. To forestall a subsequent organ dysfunction, a short-term posttraumatic down-regulation of granulocyte function has been advocated. Corticosteroids are potent and universal anti-inflammatory agents, but they have well-known side effects. Modulation of the mitogen-activated protein kinase cascade is an alternative approach. The purpose of this study was to investigate how the posttraumatic production of reactive oxygen species can be modulated by hydrocortisone or the extracellular signal-regulated kinase inhibitor U0126. DESIGN: Prospective randomized trial. SETTING: Field hospital and research laboratory. SUBJECTS: Seventeen male pigs. INTERVENTIONS: In general anesthesia, the pigs were exposed to a standardized insult: one gunshot hitting the right femur from a distance of 25 m, and one pistol shot to the left upper abdomen from close range. Following immediate first aid treatment, the animals were transported to a nearby field hospital. According to randomization, the animals received either hydrocortisone 250 mg intravenously (group 1, n = 9) or a similar amount of saline (group 2, n = 8). The injections were given 5 mins after the last shot. Blood samples were drawn before shooting, immediately before hydrocortisone was given, and 60 mins after shooting. Circulating neutrophils were isolated, and the production of reactive oxygen species was measured fluorometrically. Neutrophils from nine randomly chosen animals (five from group 1 and four from group 2) were treated in vitro with the extracellular signal-regulated kinase inhibitor U0126. MEASUREMENTS AND MAIN RESULTS: The injuries as evaluated by the abbreviated injury scale did not differ between the animals. All survived the first 60 mins. While the in vivo production of reactive oxygen species tended to increase in the controls, a significant reduction was measured in the hydrocortisone group. Subsequent treatment with U0126 further reduced the synthesis of reactive oxygen species by about two thirds in both groups, independently of time. CONCLUSIONS: Early injection of hydrocortisone after trauma inhibits the synthesis of reactive oxygen species from circulating neutrophils. Inhibition of the extracellular signal-regulated kinase branch of the mitogen-activated protein kinase signaling cascade is an alternative approach. The powerful in vitro capacity of selective extracellular signal-regulated kinase inhibitors to reduce the posttraumatic reactive oxygen species generation deserves further investigations, and compelling evidence of their in vivo usefulness is still lacking.     

Effects of a series of organosulfur compounds on mitotic arrest and induction of apoptosis in colon cancer cells

We previously reported that the garlic-derived compound S-allylmercaptocysteine (SAMC) causes growth inhibition, mitotic arrest, and induction of apoptosis in SW480 human colon cancer cells by inducing microtubule depolymerization and c-Jun NH(2) terminus kinase-1 activation. In the present study, we compared the aforementioned effects of SAMC to those of a series of garlic-derived and other organosulfur compounds. Among the 10 compounds tested, only SAMC, diallyl disulfide (DADS), and S-trityl-L-cysteine (trityl-cys) cause significant inhibition of cell growth with IC(50) values of 150, 56, and 0.9 micromol/L, respectively. These three compounds also induce G(2)-M cell cycle arrest and apoptosis. Further studies reveal that, like SAMC, the garlic-derived compound DADS exerts antiproliferative effects by binding directly to tubulin and disrupting the microtubule assembly, thus arresting cells in mitosis and triggering mitochondria-mediated signaling pathways that lead to apoptosis. However, the synthetic compound trityl-cys exerts its effect on M-phase arrest and growth inhibition by mechanisms that involve spindle impairment but do not involve disruption of microtubule structure or dynamics. Furthermore, trityl-cys does not induce marked loss of mitochondrial membrane potential or release of cytochrome c, but it does induce caspase-3 activation and poly(ADP-ribose) polymerase cleavage. Structure-function analysis suggests that both the allyl and the disulfide moieties are important features for the antiproliferative effects of SAMC and DADS. These findings may be useful in the identification, synthesis, and development of organosulfur compounds that have anticancer activity.     

Continuing education course #3: current practices and future trends in neuropathology assessment for developmental neurotoxicity testing

The continuing education course on Developmental Neurotoxicity Testing (DNT) was designed to communicate current practices for DNT neuropathology, describe promising innovations in quantitative analysis and noninvasive imaging, and facilitate a discussion among experienced neuropathologists and regulatory scientists regarding suitable DNT practices. Conventional DNT neuropathology endpoints are qualitative histopathology and morphometric endpoints of particularly vulnerable sites (e.g., cerebral, cerebellar, or hippocampal thickness). Novel imaging and stereology measurements hold promise for automated analysis of factors that cannot be effectively examined in routinely processed specimens (e.g., cell numbers, fiber tract integrity). The panel recommended that dedicated DNT neuropathology data sets be acquired on a minimum of 8 sections (for qualitative assessment) or 3 sections (for quantitative linear and stereological analyses) using a small battery of stains to examine neurons and myelin. Where guidelines permit discretion, immersion fixation is acceptable for younger animals (postnatal day 22 or earlier), and peripheral nerves may be embedded in paraffin. Frequent concerns regarding DNT data sets include false-negative outcomes due to processing difficulties (e.g., lack of concordance among sections from different animals) and insensitive analytical endpoints (e.g., qualitative evaluation) as well as false-positive results arising from overinterpretation or misreading by inexperienced pathologists.     

Self-monitoring of behaviour as a risk reduction strategy for persons living with HIV

To reduce the HIV-related transmission behaviours of persons living with HIV (PLH), a few efficacious interventions have been designed and evaluated. However, these interventions were delivered at relatively high cost, both in terms of time and resources. Given the challenges for health providers and community agencies in delivering these interventions, alternatives are needed. One possible intervention is allowing PLH to self-monitor their HIV transmission risk behaviour. Previous research suggests that self-monitoring of HIV-risk related behaviours may be a useful risk reduction strategy. This paper examines the impact of repeated risk assessments for behavioural self-monitoring as an intervention strategy for reducing sexual and substance use risk behaviours. A total of 365 PLH, recruited from community clinics, health management organizations, and health departments, completed self-assessments over time. Increased self-monitoring resulted in increases in protected sex with sexual partners of HIV-negative or unknown serostatus, and changes in attitudes conducive to reducing risk. Self-monitoring is a relatively low cost and easily implementable strategy for reducing the HIV-related transmission risk of PLH.     

Morphological evidence for vesicular glutamate release from astrocytes

There is now growing evidence that astrocytes, like neurons, can release transmitters. One transmitter that in a vast number of studies has been shown to be released from astrocytes is glutamate. Although asytrocytic glutamate may be released by several mechanisms, the evidence in favor of exocytosis is most compelling. Astrocytes may respond to neuronal activity by such exocytotic release of glutamate. The astrocyte derived glutamate can in turn activate neuronal glutamate receptors, in particular N-methyl-D-aspartate (NMDA) receptors. Here we review the morphological data supporting that astrocytes possess the machinery for exocytosis of glutamate. We describe the presence of small synaptic-like microvesicles, SNARE proteins and vesicular glutamate transporters in astrocytes, as well as NMDA receptors situated in vicinity of the astrocytic vesicles.