Regional cerebral blood flow change in a case of Alzheimer's disease with musical hallucinations

We examined alteration of regional cerebral blood flow (rCBF) in a case of Alzheimer's disease (AD) patient with musical hallucination. To detect regions related to musical hallucination, single–photon emission computed tomography (SPECT) imaging of the patient and nine sex, age, and cognitive functionmatched AD patients without delusions and hallucinations were compared using statistical parametric mapping 99 (SPM99). In comparison with controls, the patient had increased rCBF in left temporal regions and left angular gyrus. This profile could be relevant to the neuroanatomical basis of musical hallucinations. This work had been carried out at the Higher Brain Function Clinic of the Ehime University Hospital.     

Amelioration of alphavirus‐induced arthritis and myositis in a mouse model by treatment with bindarit,an inhibitor of monocyte chemotactic proteins

Objective

Alphaviruses such as chikungunya virus, Sindbis virus, o'nyong‐nyong virus, Mayaro virus, and Ross River virus (RRV), are commonly associated with arthralgias and overt arthritides worldwide. Understanding the processes by which arthritogenic viruses cause disease is a prerequisite in the quest for better treatments. In this regard, we have recently established that monocyte/macrophages are mediators of alphavirus‐induced arthritis in mice. We hypothesized that chemokines associated with monocyte/macrophage recruitment may play an important role in disease. The aim of the present investigations was to determine whether bindarit, an inhibitor of monocyte chemotactic protein (MCP) synthesis, could ameliorate alphavirus‐induced rheumatic disease in mice.

Methods

Using our recently developed mouse model of RRV‐induced arthritis, which has many characteristics of RRV disease (RRVD) in humans, the effects of bindarit treatment on RRVD in mice were determined via histologic analyses, immunohistochemistry, flow cytometry, real‐time polymerase chain reaction analysis, enzyme‐linked immunosorbent assay, and electrophoretic mobility shift assay.

Results

Bindarit‐treated RRV‐infected mice developed mild disease and had substantially reduced tissue destruction and inflammatory cell recruitment as compared with untreated RRV‐infected mice. The virus load in the tissues was not affected by bindarit treatment. Bindarit exhibited its activity by down‐regulating MCPs, which in turn led to inhibition of cell infiltration and lower production of NF‐κB and tumor necrosis factor α, which are involved in mediating tissue damage.

Conclusion

Our data support the use of inhibitors of MCP production in the treatment of arthritogenic alphavirus syndromes and suggest that bindarit may be useful in treating RRVD and other alphavirus‐induced arthritides in humans.

     

Suicide by shooting is correlated to rate of gun licenses in Austrian counties

OBJECTIVES: Shooting as method of suicide has increased considerably in Austria over recent decades and represented 23.5% of all suicides among men during the period 1990-2000. It is thought that the availability of guns could lead to their use in acts of suicide, and therefore we investigated the numbers of gun licenses (which constitutes ownership of guns and permission to carry a gun) in the nine Austrian counties and their correlation with suicides by shooting and other methods. METHODS: We studied registered suicides, including the method used, between 1990 and 2000 in Austria and the numbers of gun licenses held in the nine counties of Austria in the same period. RESULTS: We found a strong correlation between the average gun license rate for the period 1990-2000 and suicides by shooting (r = 0.967), and only very weak correlation, and for some of the years under investigation a negative correlation, with other methods of committing suicide (r = 0.117) and the suicide rate in general (r = 0.383). CONCLUSIONS: As shooting as a method of suicide has increased in Austria in recent decades, and is a highly lethal method, the finding that the shooting suicide rate is related to the extent of gun ownership deserves attention, especially as there is evidence that restriction of gun ownership is an important factor in suicide prevention.     

Usual interstitial pneumonia and chronic idiopathic interstitial pneumonia: analysis of CT appearance in 92 patients

PURPOSE: To retrospectively analyze computed tomographic (CT) findings of chronic idiopathic interstitial pneumonia (IIP) and to determine which findings are most helpful for distinguishing IIP from usual interstitial pneumonia (UIP) with univariate and multivariate analyses. MATERIALS AND METHODS: Institutional review board approval and informed consent were not required for this retrospective review of patient records and images. Two observers working independently and without knowledge of the diagnosis evaluated the extent and distribution of various thin-section CT findings (ground-glass opacity, consolidation, reticulation, and honeycombing) in 92 patients (51 men, 41 women; mean age, 56 years; age range, 29-81 years) with a histologic diagnosis of UIP (n = 20), cellular nonspecific interstitial pneumonia (NSIP) (n = 16), fibrotic NSIP (n = 16), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) (n = 11), desquamative interstitial pneumonia (DIP) (n = 15), or lymphoid interstitial pneumonia (LIP) (n = 14). Observers used univariate and multivariate statistical analyses to compare their findings with the extent and distribution of UIP. RESULTS: Observers made the correct diagnosis in 145 (79%) of 184 readings. Multivariate logistic regression analysis showed that the independent findings that distinguished UIP from cellular NSIP were the extent of honeycombing and the most proximal bronchus with traction bronchiectasis (odds ratio, 5.16 and 0.37, respectively); the finding that distinguished UIP from fibrotic NSIP was the extent of honeycombing (odds ratio, 2.10). CT features that distinguished UIP from RB-ILD and DIP included extent of ground-glass opacity (odds ratio, 0.76), thickening of bronchovascular bundles (odds ratio, 1.58), the most proximal bronchus with traction bronchiectasis (odds ratio, 0.22), and the number of segments with traction bronchiectasis (odds ratio, 3.64). CONCLUSION: UIP has a characteristic appearance that usually facilitates distinction from other types of chronic IIPs at thin-section CT. The most useful finding when differentiating UIP from NSIP was the extent of honeycombing.     

Idiopathic interstitial pneumonias: prevalence of mediastinal lymph node enlargement in 206 patients

OBJECTIVE: The purposes of our study were to determine the prevalence of mediastinal lymphadenopathy in idiopathic interstitial pneumonias, correlate their presence with high-resolution CT (HRCT) findings, and assess the potential value of mediastinal lymphadenopathy in the differential diagnosis of idiopathic interstitial pneumonias. MATERIALS AND METHODS: The study included 206 consecutive patients from three medical centers with pathologically proven idiopathic pulmonary fibrosis (n = 136), non-specific interstitial pneumonia (NSIP) (n = 47), cryptogenic organizing pneumonia (COP) (n = 16), respiratory bronchiolitis-interstitial lung disease (RB-ILD) (n = 5), and desquamative interstitial pneumonia (DIP) (n = 2). HRCT scans were retrospectively reviewed for the presence of mediastinal lymphadenopathy (short-axis diameter, >or= 10 mm), predominant parenchymal pattern, and extent of disease. RESULTS: Mediastinal lymphadenopathy was seen in 139 (67%) of 206 patients, including 90 (66%) of 136 with idiopathic pulmonary fibrosis, 38 (81%) of 47 with NSIP, six (38%) of 16 with COP, and five (71%) of seven with RB-ILD or DIP. The presence of enlarged nodes was less common in COP than in the other idiopathic interstitial pneumonias (p = 0.04). No significant difference was found in the prevalence of lymphadenopathy in patients with predominant ground-glass opacity (53%) or predominant reticulation (40%). The extent of parenchymal abnormalities was 25-50% in 74 patients (53%), 50-75% in 30 (22%), < 25% in 22 (16%), and > 75% in 13 (9%). A positive correlation between the extent of disease and presence of lymphadenopathy was seen in patients with NSIP (p = 0.01). CONCLUSION: Mediastinal lymphadenopathy is a common feature in idiopathic interstitial pneumonias, being slightly less common in COP than in the other idiopathic interstitial pneumonias. The presence of lymphadenopathy therefore has limited value in the differential diagnosis. In patients with idiopathic pulmonary fibrosis, the presence of lymph node enlargement did not correlate to any specific HRCT pattern or to the extent of disease.     

Differential effects of Down's syndrome and Alzheimer's neuropathology on default mode connectivity

Down's syndrome is a chromosomal disorder that invariably results in both intellectual disability and Alzheimer's disease neuropathology. However, only a limited number of studies to date have investigated intrinsic brain network organisation in people with Down's syndrome, none of which addressed the links between functional connectivity and Alzheimer's disease. In this cross‐sectional study, we employed ¹¹C‐Pittsburgh Compound‐B (PiB) positron emission tomography in order to group participants with Down's syndrome based on the presence of fibrillar beta‐amyloid neuropathology. We also acquired resting state functional magnetic resonance imaging data to interrogate the connectivity of the default mode network; a large‐scale system with demonstrated links to Alzheimer's disease. The results revealed widespread positive connectivity of the default mode network in people with Down's syndrome (n = 34, ages 30–55, median age = 43.5) and a stark lack of anti‐correlation. However, in contrast to typically developing controls (n = 20, ages 30–55, median age = 43.5), the Down's syndrome group also showed significantly weaker connections in localised frontal and posterior brain regions. Notably, while a comparison of the PiB‐negative Down's syndrome group (n = 19, ages 30–48, median age = 41.0) to controls suggested that alterations in default mode connectivity to frontal brain regions are related to atypical development, a comparison of the PiB‐positive (n = 15, ages 39–55, median age = 48.0) and PiB‐negative Down's syndrome groups indicated that aberrant connectivity in posterior cortices is associated with the presence of Alzheimer's disease neuropathology. Such distinct profiles of altered connectivity not only further our understanding of the brain physiology that underlies these two inherently linked conditions but may also potentially provide a biomarker for future studies of neurodegeneration in people with Down's syndrome.     

Cost‐effectiveness of cognitive therapy as an early intervention for post‐traumatic stress disorder in children and adolescents: a trial based evaluation and model

Background

Untreated post‐traumatic stress disorder (PTSD) in children and adolescents is associated with a considerable economic burden on the health system, families and society. Recent research has demonstrated the potential efficacy of cognitive therapy as an early intervention for PTSD in children and adolescents. Children who experienced a single traumatic event in the previous two to six months and were randomized to cognitive therapy for PTSD (CT‐PTSD) were significantly more likely to be PTSD‐free compared to those randomized to usual care represented by waitlist control. The current study evaluated the economic impact of improvements in the treatment of PTSD in children and adolescents.

Methods

A cost‐effectiveness analysis was conducted from the national health service/personal social services perspective with outcomes expressed as quality‐adjusted life years (QALYs). Patient level costs and outcomes were collected during the 11 week clinical trial and extrapolated to a three year time horizon using economic modelling methods. Uncertainty was estimated using probabilistic sensitivity analysis and assumptions were tested using one way sensitivity analysis.

Results

The incremental cost‐effectiveness ratio at 3 years was £2,205 per QALY with a 60%–69% probability of CT‐PTSD being cost‐effective compared to usual care at the UK £20,000 to £30,000 per QALY decision threshold.

Conclusions

This study provides preliminary evidence for the cost‐effectiveness of cognitive therapy in this treatment population. Larger pragmatic trials with longer follow‐up are indicated.     

Motor impairment rehabilitation post acquired brain injury

OBJECTIVE: We sought to investigate the efficacy of treatment strategies used to manage motor impairments following acquired brain injury (ABI) in order to provide guidance for clinical practice based on the best available evidence. METHODS AND MAIN OUTCOMES: A systematic review of the literature from 1980-2005 was conducted focusing on pharmacological, non-pharmacological, and exercise interventions available for motor impairments post ABI. The efficacy of a given intervention was classified as strong (supported by two or more randomized controlled trials (RCTs)), moderate (supported by a single RCT), or limited (supported by other types of studies in the absence of RCTs). RESULTS: Thirty-six studies examining a variety of treatment approaches for motor impairments and activity limitations following ABI were evaluated. The majority of interventions are only supported by limited evidence. However, there is strong evidence that serial casting does reduce ankle plantar contractures due to spasticity of cerebral origin, and strong evidence also suggests that partial body weight supported gait training does not provide any added benefit over conventional gait training. There is also moderate evidence to support the use of functional fine motor control retraining to improve motor coordination, tizanidine for upper and lower extremity spasticity, and specific sit-to-stand training to improve functional ability. There is also moderate evidence that casting alone is as effective as casting and Botulinum toxin injections for plantar contractures. CONCLUSIONS: Although there are a variety of treatment strategies to manage motor impairments and activity limitations following ABI, most are only supported by limited evidence pointing to the need for studies of improved methodological quality in this area.