The feasibility of statistical parametric mapping for the analysis of positron emission tomography studies using 11C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-tropane in patients with movement disorders

Movement disorders, including Parkinson's disease and parkinsonian syndromes, e.g. progressive supranuclear palsy, multiple system atrophy, and Lewy body dementia, may be difficult to differentiate among each other at an early stage, since they may share similar clinical features and response to dopaminergic drugs. As new tracers for imaging the dopamine transporters become available, the use of positron emission tomography (PET) for the differential diagnosis of movement disorders is gaining clinical relevance. Visual interpretation is generally used for PET image analysis. However, the use of some form of less subjective analysis is desirable in order to detect subtle changes that may be difficult to identify by visual interpretation and to achieve an operator independent analysis. To this end this study was aimed at assessing the feasibility of using statistical parametric mapping (SPM) for the clinical evaluation of single PET scans performed with 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)-tropane ( C-beta-CIT-FE). Eleven healthy volunteers and five patients with movement disorders (Parkinson's disease, essential tremor, PSP and Lewy body dementia) were included in this study. Each subject underwent a PET study after i.v. injection of C-beta-CIT-FE. The PET images of C-beta-CIT-FE distribution acquired between 60 and 90 min were spatially fitted into the Talairach and Tournoux space. A template of normal C-beta-CIT-FE distribution was derived from studies in the 11 normal control subjects. Different patterns of reduction of the uptake of the tracer were detected in the basal ganglia of the five patients, in relation to each pathological condition. The patterns of distribution were all consistent with the severity and type of disease. The results of this study demonstrate the feasibility of differentiating among different states of dopaminergic impairment, due to Parkinson's disease and parkinsonian syndromes, by using PET scans with C-beta-CIT-FE and by using the SPM procedure for analysis of the data.     

Complete Pathologic Response after Combined Modality Treatment for Rectal Cancer and Long-Term Survival: A Meta-Analysis

Background

Complete pathologic response (CPR) after neoadjuvant chemoradiotherapy (combined modality treatment, CMT) for rectal cancer seems associated with improved survival compared to partial or no response (NPR). However, previous reports have been limited by small sample size and single-institution design.

Methods

A systematic literature review was conducted to detect studies comparing long-term results of patients with CPR and NPR after CMT for rectal cancer. Variables were pooled only if evaluated by 3 or more studies. Study end points included rates of CPR, local recurrence (LR), distant recurrence (DR), 5-year overall survival (OS), and disease-free survival (DFS).

Results

Twelve studies (1,913 patients) with rectal cancer treated with CMT were included. CPR was observed in 300 patients (15.6%). CPR and NPR patient groups were similar with respect to age, sex, tumor size, distance of tumor from the anus, and stage of disease before treatment. Median follow-up ranged from 23 to 46?months. CPR patients had lower rates of LR [0.7% vs. 2.6%; odds ratio (OR) 0.45, 95% confidence interval (CI) 0.22?C0.90, P?=?0.03], DR (5.3% vs. 24.1%; OR 0.15, 95% CI 0.07?C0.31, P?=?0.0001), and simultaneous LR?+?DR (0.7% vs. 4.8%; OR 0.32, 95% CI 0.13?C0.79, P?=?0.01). OS was 92.9% for CPR versus 73.4% for NPR (OR 3.6, 95% CI 1.84?C7.22, P?=?0.002), and DFS was 86.9% versus 63.9% (OR 3.53, 95% CI 1.62?C7.72, P?=?0.002).

Conclusions

CPR after CMT for rectal cancer is associated with improved local and distal control as well as better OS and DFS.     

Identification of novel biomarkers differentially expressed between African-American and Caucasian-American prostate cancer patients

Prostate cancer (PCa) incidence and mortality rate vary among racial and ethnic groups with the highest occurrence in African American (AA) men who have mortality rates twice that of Caucasians (CA). In this study, we focused on differential expression of proteins in AA prostate cancer compared to CA using Protein Pathway Array Analysis (PPAA), in order to identify protein biomarkers associated with PCa racial disparity. Fresh frozen prostate samples (n=90) obtained from radical prostatectomy specimens with PCa, including 25 AA tumor, 21 AA benign, 23 CA tumor, 21 CA benign samples were analyzed. A total of 286 proteins and phosphoproteins were assessed using PPAA. By PPAA analysis, 33 proteins were found to be significantly differentially expressed in tumor tissue (n=48, including both CA and AA) in comparison to benign tissue (n=42). We further compared protein expression levels between AA and CA tumor groups and found that 3 proteins were differentially expressed (P<0.05 and q<5%). Aurora was found to be significantly increased in AA tumors, while Cyclin D1 and HNF-3a proteins were downregulated in AA tumors. Predicted risk score was significantly different between AA and CA ethnic groups using logistic regression analysis. In conclusion, we identified Aurora, Cyclin D1 and HNF-3a proteins as being differentially expressed between AA and CA in PCa tissue. Our study suggests that these proteins might be involved in different pathways that lead to aggressive PCa behavior in AA patients, potentially serving as biomarkers for the PCa racial disparity.     

High risk for sleep apnea in the Berlin questionnaire and coronary artery disease

Introduction  

Obstructive sleep apnea (OSA) affects up to 30% of the adult population and is a risk factor for coronary artery disease (CAD). The diagnostic process, involving polysomnography, may be complex. Berlin questionnaire (BQ) is a validated and economical screening tool.     

Epidemiology of hip fractures in northwestern Italy: a multicentric regional study on incidence of hip fractures and their outcome at 3-year follow-up

Piedmont is a region in northwestern Italy counting 4.2 million inhabitants. The purpose of our study was to update data on incidence and outcomes of hip fractures (HF) in our region to present days. The data of all patients affected by HF in 2003 in Piedmont (total: 5,386 patients) were analyzed, determining the incidence of HF, mean age, sex, fracture pattern and treatment adopted. Additionally, 564 patients underwent a questionnaire on comorbidities, complications, functional outcome and survivorship. Overall incidence of HF was 126.13/100,000 inhabitants-year. Mean hospitalization was 13.67 days. Mean time to surgery was 2.67 days. Survivorship was 94% at 3-month, 71.32% at 1-year and 60.21% at 3-year follow-up. These up-to-date data on HF in our region are in accordance with the international literature and could prove useful for Orthopaedic and Trauma surgeons for giving information to patients and their relatives.     

Structure of N-linked oligosaccharides attached to chlorovirus PBCV-1 major capsid protein reveals unusual class of complex N-glycans

The major capsid protein Vp54 from the prototype chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) contains four Asn-linked glycans. The structure of the four N-linked oligosaccharides and the type of substitution at each glycosylation site was determined by chemical, spectroscopic, and spectrometric analyses. Vp54 glycosylation is unusual in many ways, including: (i) unlike most viruses, PBCV-1 encodes most, if not all, of the machinery to glycosylate its major capsid protein; (ii) the glycans are attached to the protein by a β-glucose linkage; (iii) the Asn-linked glycans are not located in a typical N-X-(T/S) consensus site; and (iv) the process probably occurs in the cytoplasm. The four glycoforms share a common core structure, and the differences are related to the nonstoichiometric presence of two monosaccharides. The most abundant glycoform consists of nine neutral monosaccharide residues, organized in a highly branched fashion. Among the most distinctive features of the glycoforms are (i) a dimethylated rhamnose as the capping residue of the main chain, (ii) a hyperbranched fucose unit, and (iii) two rhamnose residues with opposite absolute configurations. These glycoforms differ from what has been reported so far in the three domains of life. Considering that chloroviruses and other members of the family Phycodnaviridae may have a long evolutionary history, we suggest that the chlorovirus glycosylation pathway is ancient, possibly existing before the development of the endoplasmic reticulum and Golgi pathway, and involves still unexplored mechanisms.     

Frontal and subcortical contribution to visual hallucinations in dementia with Lewy bodies and Parkinson’s disease

Objectives: Visual hallucinations (VH) are common in Lewy body disease (LBD), and have been associated with cognitive and structural brain alterations. Evidence so far concerns mainly Parkinson’s disease (PD), but little is known about symptom-specific pathophysiological mechanisms across the LBD spectrum, especially related to the presence of dementia. The aim of the present pilot study was to investigate the neuroanatomical, and neuropsychological characteristics related to VH in two forms of LBD, namely dementia with Lewy bodies (DLB) and PD without dementia.

Methods: Whole brain voxel-based morphometry (VBM) analyses on 3D MRI acquired structural brain scans, and neuropsychological testing were performed on 28 clinically diagnosed DLB (11 with VH, 17 NVH), and 24 PD (9 with VH, and 15 NVH) patients. In order to assess differences in gray matter (GM) regional volumes, and cognitive performance, hallucinating patients for each group were compared with corresponding non-hallucinating ones.

Results: DLB patients with VH presented significantly worse visual attention deficits compared to those without, which persisted even when controlling for visual perception. Whole brain VBM analysis revealed decreased GM volume in DLB with VH in the right superior and medial frontal gyri, putamen, caudate nucleus and insula. Subcortical regional volumes were also significantly associated with visual attention performance. Hallucinating PD patients, instead, presented more severe executive dysfunction, but VBM showed no volumetric differences between the two PD subgroups. Post hoc region of interest analyses revealed striatal GM loss in PD with VH.

Conclusion: Frontal and striatal GM atrophy may contribute to the emergence of VH in DLB, which may be fostered by the more severe attention deficits. Striatal GM loss and executive dysfunction, instead, appeared to underlie VH in PD without dementia.     

A Survey of Persons Who Use Integrated Control Devices

Integrated devices allow users to operate multiple pieces of assistive technology items from a single input device. Through this single input device, users with severe physical limitations are able to operate several other devices such as a wheelchair, telephone, computer, and communication aid. Twenty-four integrated control users completed a telephone survey to ascertain consumer satisfaction with integrated controls. Eighteen were either satisfied or very satisfied with the evaluation for an integrated control, one was neither satisfied nor dissatisfied, two were very dissatisfied, and three did not respond to the question. Twenty were very satisfied or satisfied and four were either dissatisfied or very dissatisfied with the training they received. Twenty-two respondents indicated they were either very satisfied or satisfied with their integrated control device, one was neither satisfied nor dissatisfied, and one was very dissatisfied. In general, respondents were satisfied with their integrated control devices. Specifically, respondents were satisfied with the increase in independence and the ability to control other equipment such as television sets and computers. Simplicity, touch sensitivity, and visual/auditory feedback appeared to play important roles in satisfaction.     

Consumer Participation in Identifying Research and Development Priorities for Power Wheelchair Input Devices and Controllers

A focus group comprised of persons who use power wheelchairs and professionals working in the field were asked to participate in a brainstorming session to determine priorities for the development and application of power mobility input devices and control concepts. The group consensus was that durability and reliability are the most important criteria. Essentially, the expectation is that a power wheelchair must work everyday in the way a person needs it and wants it. At the same time, there is a desire to enhance and advance the features of input devices and control systems. Many would say these changes constitute designing “smarter” power wheelchairs, such as systems that can independently detect obstacles and can provide users with more feedback. This paper presents the rationale behind forming this focus group and details of the results of a brainstorming session where ideas were generated and prioritized. The five most important issues as determined by the group are discussed in depth.