Using the BOLD MR signal to differentiate the stereoisomers of ketamine in the rat

RATIONALE: Ketamine is a chiral molecule that is reported to model aspects of schizophrenia. OBJECTIVES: To investigate the stereospecificity of the isomers of ketamine using pharmacological magnetic resonance imaging (phMRI) in order to further understand ketamine's pharmacodynamic actions. METHOD: Responses to 25 mg kg-1S(+) isomer, R(-) isomer and racemic ketamine in independent groups of Sprague-Dawley rats were investigated using a prepulse inhibition paradigm, locomotor observations, MRI and 2-deoxyglucose techniques. RESULTS: Racemic ketamine and the S(+) isomer were both capable of disrupting sensorimotor gating as measured using prepulse inhibition and produced a longer period of hyperlocomotion comparative to the R(-) isomer. In contrast, large alterations in the BOLD MR signal were observed with R(-) isomer, whereas S(+) isomer and racemate precipitated more localized BOLD signal changes predominantly in cortical, hippocampal and hindbrain regions. Glucose utilization rates in conscious animals are in agreement with previously published data and verify the BOLD responses in the racemic group. However, no significant changes in glucose utilization were observed in the anesthetized cohort. CONCLUSIONS: Ketamine and its isomers have stereospecific effects on sensorimotor gating and locomotion that correlate with the enantiomer's affinity for the NMDA receptor. It would appear that anesthesia, as required for preclinical MRI procedures, may interact with and potentially attenuate the drug's response. Although analysis of the main effect of isomers in comparison to each other or the racemate offers an alternative analysis method that should be less susceptible to anesthetic interactions, only the R(-) isomer comparative to the racemate offers significant differences of interest.     

Nonredundant roles of antibody,cytokines, and perforin in the eradication of established Her-2/neu carcinomas

Since the mechanisms by which specific immunity destroys Her-2/neu carcinoma cells are highly undetermined, these were assessed in BALB/c mice vaccinated with plasmids encoding extracellular and transmembrane domains of the protein product (p185(neu)) of the rat Her-2/neu oncogene shot into the skin by gene gun. Vaccinated mice rejected a lethal challenge of TUBO carcinoma cells expressing p185(neu). Depletion of CD4 T cells during immunization abolished the protection, while depletion of CD8 cells during the effector phase halved it, and depletion of polymorphonuclear granulocytes abolished all protection. By contrast, Ig mu-chain gene KO mice, as well as Fcgamma receptor I/III, beta-2 microglobulin, CD1, monocyte chemoattractant protein 1 (MCP1), IFN-gamma, and perforin gene KO mice were protected. Only mice with both IFN-gamma and perforin gene KOs were not protected. Although immunization also cured all BALB/c mice bearing established TUBO carcinomas, it did not cure any of the perforin KO or perforin and IFN-gamma KO mice. Few mice were cured that had knockouts of the gene for Ig mu-chain, Fcgamma receptor I/III, IFN-gamma, or beta-2 microglobulin. Moreover, vaccination cured half of the CD1 and the majority of the MCP1 KO mice. The eradication of established p185(neu) carcinomas involves distinct mechanisms, each endowed with a different curative potential.     

Diagnosis of sacroiliac joint pain: validity of individual provocation tests and composites of tests

Previous research indicates that physical examination cannot diagnose sacroiliac joint (SIJ) pathology. Earlier studies have not reported sensitivities and specificities of composites of provocation tests known to have acceptable inter-examiner reliability. This study examined the diagnostic power of pain provocation SIJ tests singly and in various combinations, in relation to an accepted criterion standard. In a blinded criterion-related validity design, 48 patients were examined by physiotherapists using pain provocation SIJ tests and received an injection of local anaesthetic into the SIJ. The tests were evaluated singly and in various combinations (composites) for diagnostic power. All patients with a positive response to diagnostic injection reported pain with at least one SIJ test. Sensitivity and specificity for three or more of six positive SIJ tests were 94% and 78%, respectively. Receiver operator characteristic curves and areas under the curve were constructed for various composites. The greatest area under the curve for any two of the best four tests was 0.842. In conclusion, composites of provocation SIJ tests are of value in clinical diagnosis of symptomatic SIJ. Three or more out of six tests or any two of four selected tests have the best predictive power in relation to results of intra-articular anaesthetic block injections. When all six provocation tests do not provoke familiar pain, the SIJ can be ruled out as a source of current LBP.     

Evaluation of a web-based palliative care pain management module for housestaff

The objectives of this study were to determine internal medicine residents' knowledge of outpatient palliative care pain management, describe the association of level of training with knowledge, and evaluate the impact on knowledge of a web-based, interactive, evidence-based educational module. We developed the module using established educational principles, based on review of other educational materials, guidelines, and the medical literature. The module included pretest and post-test questions, case studies, didactic sections, and web links. Six hundred twelve housestaff in 35 training programs in 19 states completed the module during the 2005–2006 academic year (196 [32.0%] postgraduate year [PGY]-1, 200 [32.7%] PGY-2, and 216 [35.3%] PGY-3). The mean pretest score was 54.4% (range 31.1%–84.6%); scores were lowest for specific pain management knowledge questions, including appropriate titration of breakthrough opioid doses (mean 31.1% correct) and appropriate initial use of opioids (40.7% correct). Pretest scores were not significantly different by level of training (52.2% for PGY-1 and 56.7% for PGY-3). The mean post-test score was 72.8%, a statistically significant increase from the pretest overall (P < 0.001) and for seven of the 10 learning objectives (P < 0.001). These findings indicate that housestaff lacked knowledge in many areas of palliative care pain management, and knowledge did not increase with time spent in residency. The large increase in test scores after the module suggests that this may be an effective component of a comprehensive palliative care curriculum.     

The effects of additive solution pH and metabolic rejuvenation on anaerobic storage of red cells

BACKGROUND: Red cell (RBC) storage can be extended to 9 weeks under anaerobic or alkaline conditions. Simultaneous use of these approaches has not provided additive benefit. Our objective was to determine whether anaerobic storage with acidified additive solution (AS) coupled with metabolic rejuvenation might further improve the benefits of anaerobic storage. STUDY DESIGN AND METHODS: RBC storage in AS with a pH value of 6.5, 7.4, or 8.3 in aerobic or anaerobic conditions was examined using a panel of in vitro biochemical and RBC markers. RBC rejuvenation during cold storage was also evaluated. A randomized crossover radiolabeled recovery study (eight subjects) evaluated anaerobic RBC storage using AS65 with cold rejuvenation for up to 16 weeks of storage. RESULTS: Adenosine triphosphate (ATP) and diphosphoglycerate acid (DPG) were better maintained in anaerobic storage than in aerobic storage. Acidic or neutral AS preserved ATP concentration better, while a neutral or basic pH AS favored maintenance of DPG levels at higher levels for a longer period. AS pH had less of an effect on exposure of phosphatidylserine (PS), vesicle protein release, and hemolysis. Rejuvenation of RBCs during cold, anaerobic storage resulted in increases in ATP and DPG levels and a reversal of PS exposure. Anaerobic storage of RBCs in pH 6.5 AS rejuvenated at 7 weeks of storage yielded RBC 24‐hour recoveries of 77.3 ± 12.5 percent after 10 weeks' storage time. After a second rejuvenation at Week 11, six subjects' units demonstrated a recovery of 75.9 ± 7.3 percent at 12 weeks of storage. CONCLUSION: Extended RBC storage may be achieved using anaerobic conditions combined with low‐pH AS and rejuvenation during storage.     

Increased Tidal Volume Variability in Children is a Better Marker of Opioid-Induced Respiratory Depression than Decreased Respiratory Rate

OBJECTIVE: During opioid administration, decreasing respiratory rate is typically used as a predictor of respiratory depression. Prior to opioid-induced apnea, progressively irregular breathing patterns have been noticed. We hypothesize that opioid administration to children will increase tidal volume variability (TV(var)) and that this will be a better predictor of respiratory depression than a decrease in respiratory rate. METHODS: We recruited 32 children aged 2-8 years scheduled to undergo surgery. During spontaneous ventilation, flow rates and respiratory rates were continuously recorded, while remifentanil was infused at stepwise increasing doses each lasting 10 min. The infusion was continued until the patient showed signs of respiratory depression. Flow data from each dose was used to calculate tidal volumes, from which TV(var) was calculated. The respiratory rate and TV(var) during the last (D(last)), second to last (D-2), and third to last (D-3), administered doses were compared to those during baseline (fourth to last dose). We chose a threshold of TV(var) increase and compared it to a decrease in respiratory rate below 10 breaths per min as predictors of respiratory depression. RESULTS: Compared to baseline, the TV(var) increased by 336% and 668% during D(-2) and D(last), respectively, whereas respiratory rate decreased by 14.3%, 31.7%, and 55.5% during D(-3), D(-2), and D(last), respectively. A threshold increase in TV(var) of 150% over baseline correctly predicted respiratory depression in 41% of patients, compared to a drop in respiratory rate correctly predicting 22% of patients. CONCLUSIONS: TV(var) increases as children approach opioid-induced respiratory depression. This is a more useful predictor of respiratory depression than a fall in respiratory rate because the TV(var) increase is 10 times the drop in respiratory rate. A TV(var) increase also correctly predicts respiratory depression twice as often as decreased respiratory rate and is independent of age-related alterations in physiologic respiratory rates.     

Truth cube: establishing physical standards for soft tissue simulation

Accurate real-time models of soft tissue behavior are key elements in medical simulation systems. The need for fast computation in these simulations, however, often requires simplifications that limit deformation accuracy. Validation of these simplified models remains a challenge. Currently, real-time modeling is at best validated against finite element models that have their own intrinsic limitations. This study develops a physical standard to validate real-time soft tissue deformation models. We took CT images of a cube of silicone rubber with a pattern of embedded Teflon spheres that underwent uniaxial compression and spherical indentation tests. The known material properties, geometry and controlled boundary conditions resulted in a complete set of volumetric displacement data. The results were compared to a finite element model analysis of identical situations. This work has served as a proof of concept for a robust physical standard for use in validating soft tissue models. A web site has been created to provide access to our database: http://biorobotics.harvard.edu/truthcube/ (soon to be http://www.truthcube.org).     

Community mental health care: documenting the role of the nurse

In Australia, the process of deinstitutionalisation has resulted in the closure or downsizing of many large stand-alone psychiatric hospitals. The aim of modern community mental health care is to provide treatment and rehabilitation for people, who have a mental illness, in their local community. This aim is supported by the Australian National Mental Health Strategy that outlines the importance of health professionals, carers, and consumers working together to obtain the best therapeutic outcomes. This study was undertaken to obtain information regarding the current role of the community mental health nurse (CMHN). All community mental health nurses working in the Adult Program at the Directorate of Mental Health Services, Fremantle Hospital and Health Service in Western Australia participated in the study. The study was completed in November 2000. The results showed that the CMHNs' role focused on six main areas. These areas included the day-to-day management of clients, working with carers and their families; crisis work for both existing andfirst time contacts; as well as liaison and advocacy work. Thefinding of this study demonstrate CMHN's work most often with acutely ill and psychotic patients and theirfamilies. Therefore, CMHN's play a pivotal role in promoting and sustaining the philosophy of community mental health care. In addition, the liaison work within the community completed by CMHN's is vital to address the mental health needs of the community and to reduce the stigma associated with mental illness. The documentedfindings of this study provide challengesfor thefurther expansion of the CMHN's role and the development of best practice initiatives in community mental health care.     

Home Telehealth Uptake and Continued Use Among Heart Failure and Chronic Obstructive Pulmonary Disease Patients: a Systematic Review

Background

Home telehealth has the potential to benefit heart failure (HF) and chronic obstructive pulmonary disease (COPD) patients, however large-scale deployment is yet to be achieved.

Purpose

The aim of this review was to assess levels of uptake of home telehealth by patients with HF and COPD and the factors that determine whether patients do or do not accept and continue to use telehealth.

Methods

This research performs a narrative synthesis of the results from included studies.

Results

Thirty-seven studies met the inclusion criteria. Studies that reported rates of refusal and/or withdrawal found that almost one third of patients who were offered telehealth refused and one fifth of participants who did accept later abandoned telehealth. Seven barriers to, and nine facilitators of, home telehealth use were identified.

Conclusions

Research reports need to provide more details regarding telehealth refusal and abandonment, in order to understand the reasons why patients decide not to use telehealth.