Local and systemic effects of a silver nitrate coated indwelling pleural catheter in an animal model of pleurodesis.

Purpose/Aim of the study: This study assessed the safety and potential toxicity of a silver nitrate coated indwelling pleural catheter (SNCIPC) designed to create pleurodesis in a large animal model. MATERIALS AND METHODS: Sixteen animals underwent insertion of either a SNCIPC or an uncoated silicone catheter. Half of the animals were sacrificed at day 7 and the others at day 30. Animal weight and assessment of well-being, pleural fluid and blood collection were performed at regular intervals. Pleurodesis was assessed at necropsy and histopathological examination of organs performed. RESULTS: No mortality or significant clinical findings were observed throughout the experiment. SNCIPC treated animals had increased pleural fluid drainage overall (p < 0.001) and specifically on days 1-4. No differences in hemoglobin, white blood cell count or neutrophil counts were detected between groups. No treatment related histological findings were observed in any of the evaluated tissues outside of the treated area. Serum silver levels in SNCIPC catheter treated animals peaked on Day 4 (0.185 µg/mL, 30 day group) then gradually decreased for the remainder of the study period. The highest tissue silver concentrations were noted in the SNCIPC groups in tissues close to the treatment site in addition to the liver (59.8ug/g +/- 8.6 and 73.3ug/g +/- 25). Pleurodesis scores were significantly higher in SNCIPC treated animals for both the 7 day (median 6.5 vs. 1.0, p = 0.029) and 30 day cohorts (median 7.0 vs. 1.5, p = 0.029). CONCLUSIONS: SNCIPC are well tolerated and not associated with any significant signs of toxicity. Silver levels were elevated in local tissues, serum and liver but without evidence of pathological impact. Effective pleurodesis was present by day 7 and more established by day 30. Clinical studies to investigate the safety and efficacy of this device in patients with malignant pleural effusions appear warranted.

Development of a Functional Observational Battery in the Minipig for Regulatory Neurotoxicity Assessments.

A functional observational battery (FOB) is recommended as the first-tier neurotoxicity screening in the preclinical safety pharmacology testing guidelines. Minipigs have increasingly been used in regulatory toxicology studies; however, no current FOB protocol is available for neurotoxicity testing in these species. Hence, a minipig FOB instrument was developed. A complete crossover study with Sinclair minipigs was performed to evaluate physiologic, neurologic, and behavioral effects of amphetamine, ketamine, and diazepam. The treated minipigs were first observed in their home cage, were video-recorded for 10 minutes in an open field, and then went through a complete neurologic examination. Both ketamine and diazepam were shown to reduce the freezing and behavior shifts of treated minipigs, while increasing their exploratory behaviors. Both drugs also caused muscular and gait impairment. The effects of ketamine and diazepam were consistent with their roles as central nervous system (CNS) suppressants. Unique effects were also observed with ketamine and diazepam treatments, which may reflect their unique mechanisms of action. Consistent with its role as a CNS stimulant, amphetamine caused the treated minipigs to be hyperactive and to display increased freezing and behavior shifts and reduced exploring activities. These effects of amphetamine were opposite to those observed with ketamine and diazepam. Amphetamine also increased locomotion in the treated minipigs. The present effects of amphetamine, ketamine, and diazepam are in agreement with observations by others. In conclusion, the minipig is a suitable species for FOB evaluation of pharmaceuticals in preclinical safety pharmacology testing.

Bacillus Calmette-Guérin vaccination reduces the severity and progression of tuberculosis in badgers.

Control of bovine tuberculosis (TB) in cattle has proven particularly challenging where reservoirs of infection exist in wildlife populations. In Britain and Ireland, control is hampered by a reservoir of infection in Eurasian badgers (Meles meles). Badger culling has positive and negative effects on bovine TB in cattle and is difficult, costly and controversial. Here we show that Bacillus Calmette-Guérin (BCG) vaccination of captive badgers reduced the progression, severity and excretion of Mycobacterium bovis infection after experimental challenge. In a clinical field study, BCG vaccination of free-living badgers reduced the incidence of positive serological test results by 73.8 per cent. In common with other species, BCG did not appear to prevent infection of badgers subjected to experimental challenge, but did significantly reduce the overall disease burden. BCG vaccination of badgers could comprise an important component of a comprehensive programme of measures to control bovine TB in cattle.

A comparative analysis of completed suicide using high resolution brain SPECT imaging.

The authors compared regional cerebral blood flow in the brains of 12 psychiatric patients who completed the act of suicide with groups of healthy and nonsuicidal depressed subjects using statistical parametric mapping. Results were consistent with prior imaging studies on depression and were indicative of impaired impulse control and limbic dysregulation, including significant perfusion deficits in the medial prefrontal and subgenual areas (Brodmann's areas 11, 25) and ventral tegmentum. These results warrant further research.

Predicting positive and negative treatment responses to stimulants with brain SPECT imaging.

The goal of this study was to test whether clinician-rated regional cerebral blood flow (rCBF) as rendered by SPECT imaging is a meaningful predictor of patient response to CNS stimulants. Chart reviews were used to identify patients who reported prior significant positive and negative responses to CNS stimulants. Each patient in the study had received resting and concentration SPECT scans using Tc99m exametazime. Differences in cerebral blood flow for frontal regions of interest were assessed in three conditions (resting, concentration, and their difference, or "delta") using ANCOVAs and age-matched ANOVAs. Prefrontal pole deltas were found to be highly sensitive and specific predictors of response to CNS stimulants, with pole activation predicting adverse responses and pole deactivation predicting good responses. Positive and negative predictive values were greater than .75 for both poles. We conclude that SPECT renderings of rCBF, particularly in the prefrontal cortex, are a potentially powerful clinical tool for anticipating response to stimulant medications, both positive and adverse.

Preliminary evidence differentiating ADHD using brain SPECT imaging in older patients.

The objective of this study was to differentiate ADHD patients from a healthy comparison group using high resolution brain SPECT imaging in older patients. Using extensive chart reviews of structured interviews, DSM-IV criteria, and psychiatrist-given diagnoses, we identified 27 patients over age 50 with ADHD, either combined or inattentive types. Patients were compared to an age-matched group of healthy subjects with brain SPECT imaging at rest and during concentration using semiquantitative visual readings. Significantly lower cortical activity is noted in the ADHD group, particularly in the prefrontal poles, orbits, and parietal lobes. Older ADHD patients can be discerned from healthy subjects using brain SPECT. The results support the executive dysfunction model of ADHD.

Acute and chronic toxicity of nitrate to early life stages of lake trout (Salvelinus namaycush) and lake whitefish (Coregonus clupeaformis).

The acute and chronic toxicity of the nitrate ion (NO3-) to the embryos, alevins, and swim-up fry of lake trout (Salvelinus namaycush) and lake whitefish (Coregonus clupeaformis) were tested in laboratory aquaria. The acute (96-h) median lethal concentration (LC50) for swim-up fry was 1,121 mg NO3-N/L for lake trout and 1,903 mg NO3-N/L for lake whitefish. The chronic (approximately 130-150-d) LC50s for embryos to swim-up fry were 190 and 64 mg NO3-N/L, respectively. Sublethal effects on developmental timing and fry body size were observed at concentrations of 6.25 and 25 mg NO3-N/L, respectively, in the chronic tests. These results confirm that the Canadian nitrate water-quality guideline of 2.9 mg NO3-N/L, which was derived from chronic tests on a temperate-zone amphibian, is applicable to the early life stages of two species of Arctic fish. However, it does not support use of the guideline for acute exposures during early life stages of salmonid fish or for acute or chronic exposures to adult fish, which are relatively insensitive to nitrate.

What is eHealth (5): a research agenda for eHealth through stakeholder consultation and policy context review.

BACKGROUND: In 2003, the National Health Service in England and Wales, despite its large investment in information and communication technology, had not set a national research agenda. The National Health Service has three main research and development programs: one is the Service Delivery and Organisation program, commissioned in 2003, and the others are two parallel "scoping exercises" to help set a research agenda. This paper reports on one of those projects. A parallel literature review was carried out by others and has been reported elsewhere. OBJECTIVE: The objective was to explore the concerns of stakeholders and to review relevant policy in order to produce recommendations and a conceptual map of eHealth research. METHODS: There were two parallel strands. For the stakeholder consultation, 37 professionals representing 12 "stakeholder" groups participated in focus groups or interviews. Discussion was prompted by eHealth "scenarios" and analyzed using thematic content analysis. Subsequently, 17 lay participants, in three focus groups, discussed and prioritized these themes. For the policy review, 26 policy makers were interviewed, and 95 policy documents were reviewed. Recommendations were subsequently reviewed in a conference workshop. Recommendations for research from both strands were combined into a conceptual map. RESULTS: Themes from stakeholder consultation and policy review were combined as 43 recommendations under six headings. Four of these headings (using, processing, sharing, and controlling information) describe the scope of eHealth research. The other two relate to how research should be carried out (ensuring best practice is first identified and disseminated) and to the values considered important by stakeholders (in particular, measuring improvement in health). CONCLUSIONS: The scope of eHealth research (using, processing, sharing, controlling information) derived empirically from this study corresponds with "textbook" descriptions of informatics. Stakeholders would like eHealth research to include outcomes such as improved health or quality of life, but such research may be long term while changes in information technology are rapid. Longer-term research questions need to be concerned with human behavior and our use of information, rather than particular technologies. In some cases, "modelling" longer-term costs and benefits (in terms of health) may be desirable.

Cerebral blood flow changes during chanting meditation.

PURPOSE: To examine changes in brain physiology during a chanting meditation practice using cerebral blood flow single-photon emission computed tomography. METHODS: Single-photon emission computed tomography scans were acquired in 11 healthy individuals during either a resting state or meditation practice randomly performed on two separate days. Statistical parametric mapping analyses were conducted to identify significant changes in regional cerebral blood flow (rCBF) between the two conditions. RESULTS: When the meditation state was compared with the baseline condition, significant rCBF increases were observed in the right temporal lobe and posterior cingulate gyrus, and significant rCBF decreases were observed in the left parietotemporal and occipital gyri. CONCLUSION: The results offer evidence that this form of meditation practice is associated with changes in brain function in a way that is consistent with earlier studies of related types of meditation as well as with the positive clinical outcomes anecdotally reported by its users.

An analysis of regional cerebral blood flow in impulsive murderers using single photon emission computed tomography.

The authors explored differences in regional cerebral blood flow in 11 impulsive murderers and 11 healthy comparison subjects using single photon emission computed tomography. The authors assessed subjects at rest and during a computerized go/no-go concentration task. Using statistical parametric mapping software, the authors performed voxel-by-voxel t tests to assess significant differences, making family-wide error corrections for multiple comparisons. Murderers were found to have significantly lower relative rCBF during concentration, particularly in areas associated with concentration and impulse control. These results indicate that nonemotionally laden stimuli may result in frontotemporal dysregulation in people predisposed to impulsive violence.

Allergic rhinitis and its effect on sleep, fatigue, and daytime somnolence.

OBJECTIVE: To examine the adverse effects of sleep impairment on the quality of life of patients with the disorder and how these effects can be treated with therapies targeted at the underlying problems that influence sleep. DATA SOURCES: Medline and Ovid search for sleep and rhinitis. STUDY SELECTION: All literature on this topic were reviewed, and, if significant, were incorporated into this review. RESULTS: Intranasal corticosteroids used as treatment for allergic rhinitis have been shown to reduce the nasal congestion characteristic of the disorder. Data on sleep-related end points from clinical trials on intranasal corticosteroids also reveal that the treatment's effectiveness in alleviating nasal congestion leads to better sleep, reduced daytime somnolence, and improved quality of life. CONCLUSION: Further research, specifically using sleep measurements as primary end points, is needed to definitively show that intranasal corticosteroids reduce nasal congestion, thereby improving sleep and, consequently, quality of life in patients with allergic rhinitis. These future trials will serve to identify the most effective therapies that target the adverse effects of sleep impairment in this disorder.

High-resolution brain SPECT imaging and eye movement desensitization and reprocessing in police officers with PTSD.

Eye movement desensitization and reprocessing (EMDR) has been shown to be an effective treatment for posttraumatic stress disorder (PTSD). In this study, the authors evaluated the effectiveness and physiological effects of EMDR in police officers involved with on-duty shootings and who had PTSD. Six police officers involved with on-duty shootings and subsequent delayed-onset PTSD were evaluated with standard measures, the Posttraumatic Stress Diagnostic Scale, and high-resolution brain single photon emission computed tomography (SPECT) imaging before and after treatment. All police officers showed clinical improvement and marked reductions in the Posttraumatic Stress Diagnostic Scale Score (PDS). In addition, there were decreases in the left and right occipital lobe, left parietal lobe, and right precentral frontal lobe as well as significant increased perfusion in the left inferior frontal gyrus. In our study EMDR was an effective treatment for PTSD in this police officer group, showing both clinical and brain imaging changes.