Cognitive profiles of individual patients with Parkinson's disease and dementia: comparison with dementia with lewy bodies and Alzheimer's disease.

We describe the pattern of cognitive profiles within a community-based sample of patients with Parkinson's disease (PD) and dementia (PDD) using cluster analyses, and compare the results with data from patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Fifty patients with PDD and 39 with AD from Stavanger, Norway, and 62 patients with DLB from San Diego, CA, USA were diagnosed by either standardized clinical procedures or criteria (all PDD and all AD cases) or necropsy (all DLB cases). Four subgroups were identified: two subgroups with a subcortical cognitive profile (one with mild and one with moderate dementia severity), one subgroup with global impairment and severe dementia, and one subgroup with a cortical cognitive profile and moderate dementia. Of the patients with PDD and with DLB, 56% and 55%, respectively, had a subcortical cognitive profile, compared with only 33% of the AD patients. Conversely, 30% of the patients with PDD and 26% of those with DLB had a cortical cognitive profile, compared with 67% of the patients with AD. These findings suggest that in some patients with PDD, frontosubcortical changes are the main contributing factor to dementia, whereas in other patients, cortical and hippocampal changes are more important.     

Dynamic evaluation of 18F-FDG uptake by microPET and whole-body autoradiography in a fibrosarcoma-bearing mouse model.

BACKGROUND AND PURPOSE: Fluorine-18-2-deoxy-D-glucose (18F-FDG) has been used in the clinic as a diagnostic radiotracer for monitoring many kinds of tumors, but its value for monitoring fibrosarcoma is not well established. METHODS: In this study, the uptake of 18F-FDG in a fibrosarcoma-bearing mouse model was evaluated using the high resolution positron emission tomography (PET) system microPET. Tumor cells were implanted in 3 FVB/N mice, and static microPET scanning was performed on day 1, 7, 12 and 15 after implantation. A dynamic microPET image was scanned on day 12 to determine the 18F-FDG uptake in 3 other tumor-bearing mice. Time-activity curves were plotted by drawing regions of interest in the tumor, liver, kidneys and muscles. The mice were sacrificed after dynamic microPET imaging and whole-body autoradiography (WBAR) was performed. For biodistribution study, 9 tumor-bearing mice, 3 per experimental group, were studied at 3 time points and the results were compared with the static microPET images. RESULTS: MicroPET images suggested that 18F-FDG could be used to monitor the growth of tumors 7 days after implantation. Dynamic scans of 18F-FDG uptake reached a plateau in the tumor after 20 minutes on day 12 after implantation. Both microPET and WBAR revealed evidence of tumor necrosis. The results of biodistribution and WBAR agreed with those from microPET images. CONCLUSION: MicroPET was useful for monitoring the growth of fibrosarcoma and determination of the maximal uptake time point of 18F-FDG in tumors in this tumor-bearing mouse model.     

Prognostic role of alveolar-arterial oxygen pressure difference in acute pulmonary embolism.

BACKGROUND: This study investigated the utility of the alveolar - arterial oxygen pressure difference (AaDO (2)) in predicting the short-term prognosis of acute pulmonary embolism (PE). METHODS AND RESULTS: This study retrospectively enrolled 114 consecutive patients with acute PE, diagnosed by either spiral computed tomography or high probability ventilation - perfusion lung scans. During the first 24 h of admission, all patients had initial artery blood gas collected under room air. Patient exclusion criteria were chronic lung disease, septic emboli, and moderate and low probability lung scans. Patients were assigned to 2 groups based on either 30-day death or a 30-day composite event. Receiver operating characteristic analyses was used to determine the AaDO(2) cut-off value for predicting primary and composite endpoints. Statistical analysis demonstrated significant differences in AaDO(2) between the 30-day composite endpoint group and the 30-day composite event-free survival group (p=0.012). The AaDO(2) had a strong trend between the 30-day death group and the survival group (p=0.062). The best cut-off value for AaDO(2) was 53 mmHg and using this, the positive predictive value for 30-day death was 25% and the negative predictive value was 92%. For the 30-day composite endpoint, the positive predictive value for AaDO(2) was 35%, and the negative predictive value was 84%. In this study, thrombocytopenia was also an indicator of poor prognosis for patients with acute PE. CONCLUSION: The AaDO(2) measurement is a highly useful and simple measurement for predicting short-term prognosis in patients with acute PE. It has high negative predictive value and moderate positive predictive value for 30-day death and 30-day composite event. Aggressive thrombolytic treatment strategies should be considered for patients with an initial poor prognostic parameter (ie, AaDO(2) >or=53 mmHg).     

Examining preferences for allocating health care gains

This study is part of a programme to elicit and examine community preferences for health care in different contexts. Data were obtained from a group of predominantly Australian health care decision-makers. A short questionnaire contained six valuation questions and four demographic questions. The six valuation questions posed choices where equal health gains were to be allocated to different population groups based upon: age; sex; current health; socio-economic status; across time; and across different numbers of individuals. The results provide some evidence that respondents were prepared to discriminate between health gains derived in different contexts especially where health gains were to be allocated between groups of different health status and over time. Further research is planned and the possible implications for health policy, and in particular for resource allocation in health care, are briefly discussed.     

ADAMTS-4 activity on a proteoglycan vs. a polypeptide is controlled by the ancillary domains

Introduction In combination with the catalytic domain, the ancillary domains of the ADAMTS' are proposed to regulate activity via interactions with sulfated GAGs, the extracellular matrix (ECM) and cell surface. Interactions with both GAGs and the ECM have been attributed to the thrombospondin (TSP) type 1 motifs and spacer region ( Kuno and Matsushima 1998 ; Flannery et al. 2002 ). ADAMTS‐1, ‐4 and ‐5, all undergo cleavage within their respective spacer regions ( Flannery et al. 2002 ; Rodriguez‐Manzaneque et al. 2000 ; Georgiadis et al. 2002 ), an event which has been reported to increase activity towards the interglobular domain of aggrecan and decrease the heparin affinity of ADAMTS‐4 ( Flannery et al. 2002 ; Gao et al. 2002 ). Materials and methods V5‐ and His‐tagged recombinant human ADAMTS‐4 constructs terminating after the catalytic (?DTS), disintegrin‐like (?TS), TSP (?S) or spacer region (Full) were expressed in High‐Five cells. Proteoglycanase activities of the resultant proteins were assayed with solution digests of aggrecan and a polyacrylamide‐entrapped aggrecan particle assay. Proteolytic activity was measured using a novel, nonglycosylated, reporter substrate assay. Results All forms of ADAMTS‐4 were active to varying degrees in the reporter substrate assay. Digestion of aggrecan in solution digests was apparent in all proteins with the exception of the catalytic domain in isolation (?DTS). Activity towards aggrecan decreased with increasing truncation of the protein. Discussion Removal of the cysteine‐rich‐spacer domain and further C‐terminal truncations decrease the activity of ADAMTS‐4 towards aggrecan, whilst the proteolytic activity remains intact. Cleavages releasing the ancillary domains of ADAMTS' may therefore alter the catalytic activity of these enzymes against proteoglycans and also nonglycosylated polypeptides. More information is required about potential substrates for the processed forms of ADAMTS‐4.     

The '2-week rule' for suspected breast carcinoma: a qualitative study of the views of patients and professionals.

BACKGROUND: The '2-week rule' for the referral of patients with potential cancers is an important but controversial development. AIMS: To investigate the 2-week rule for women with breast problems from the perspective of the patients and of healthcare professionals. DESIGN OF STUDY: Qualitative study using semi-structured interviews. SETTING: Patients referred to two breast care units and professionals from primary and secondary care in Teesside and Hartlepool. METHOD: Semi-structured interviews with a purposive sample of 12 patients referred under the 2-week rule and 20 professionals. RESULTS: All women experienced considerable worries in the time leading up to diagnosis. This affected relationships with others, and they used selective telling to help maintain control over their own anxiety and prevent anxiety in others. They were not aware of the 2-week rule as a new initiative, but wanted quick referral to assure them that they did not have cancer. Patients felt they needed more information about breast symptoms and the referral process. Comments about communication with professionals, both good and poor, were frequent in their accounts, which contrasted with the absence of such concerns in the accounts of the professionals. The professionals thought that the 2-week rule was advantageous in reducing anxiety, but thought that disadvantages included longer waits for patients referred outside the rule and increased pressure on hospital services. Cultural changes, including increased patient assertiveness and 'breast awareness', were considered important contextual factors. General practitioners (GPs) were concerned about missing diagnoses in patients statistically unlikely to have carcinomas. CONCLUSION: Differences in emphasis were apparent, with patients wanting to be assured that they did not have cancer, specialists concerned both about increased workload and the impact on patients with cancers, and GPs anxious about missing diagnoses. The 2-week rule compromises professional autonomy, which partially accounts for the anger directed against it. There is a need for patients to have more information, and they place great value on good communication. All patient responders experienced significant distress while waiting to be seen.     

Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.

BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.