A randomised crossover trial of minimising medical terminology in secondary care correspondence in patients with chronic health conditions: impact on understanding and patient reported outcomes.

BACKGROUND: There is little existing research on the role that secondary care letters have in ensuring patient understanding of chronic health conditions. AIM: To determine whether minimising the use of medical terminology in medical correspondence improved patient understanding and anxiety/depression scores. METHODS: A single-centre, non-blinded, randomised crossover design assessed health literacy, EQ-5D scores and the impact of the 'translated' letter on the doctor's professionalism, the patient's relationship with their general practitioner (GP) and their perceived impact on chronic disease management. Patients were crossed over between their 'translated' and original letter. RESULTS: Sixty patients were recruited. Use of a 'translated' letter reduced mean terms not understood from 7.78 to 1.76 (t(58) = 4.706, P < 0.001). Most patients (78.0%) preferred the 'translated' letter, with 69.5% patients perceiving an enhancement in their doctor's professionalism (z = 2.864, P = 0.004), 69.0% reporting a positive influence on relationship with their GP (z = 2.943, P = 0.003) and 79.7% reporting an increase in perceived ability to manage their chronic health condition with the 'translated' letter (z = 4.601, P < 0.001). There was no effect on EQ-5D depression/anxiety scores. CONCLUSION: Minimising the use of medical terminology in medical correspondence significantly improved patient understanding and perception of their ability to manage their chronic health condition. Although there was no impact on EQ-5D depression/anxiety scores, overwhelming patient preference for the 'translated' letter indicates a need for minimisation of medical terminology in medical correspondence for patients with chronic health conditions.

Primary leiomyosarcoma in the heart of a guinea pig.

Leiomyosarcoma was diagnosed in the heart of a 3-year-old female guinea pig. Neoplastic tissue was located in the ventricular septum extending into the right ventricular lumen, but was not obvious grossly. Microscopically, the mass was nodular and infiltrative and was composed of streams and bundles of spindle cells. Immunohistochemically, the neoplastic cells expressed vimentin and α-smooth muscle actin. There was no cross striation of the muscle cells. This is the first report of cardiac leiomyosarcoma in a guinea pig.

Evaluation of high-definition and conventional oscillometric blood pressure measurement in anaesthetised dogs using ACVIM guidelines.

OBJECTIVES: To evaluate high-definition and conventional oscillometry in comparison with direct blood pressure measurements in anaesthetised dogs. METHODS: Eight simultaneous readings for systolic, diastolic and mean pressure were obtained directly and with each of two devices in nine anaesthetised dogs. Measurement procedure and validation were based on the 2007 ACVIM guidelines. RESULTS: Sixty-three simultaneous readings were evaluated for each device and direct measurements. The mean differences (bias) to direct values were within 10 mmHg for both devices although bias for systolic and diastolic blood pressures was higher for Memodiagnostic. The standard deviations of differences (precision) were within 15 mmHg for Dinamap but exceeded for Memodiagnostic. Correlation coefficients were higher for Dinamap than Memodiagnostic but both failed to reach a correlation of 0.9. Over 50% of values lay within 10 mmHg of direct measures for both devices, but this percentage was greater for Dinamap than Memodiagnostic. Over 80% of values lay within 20 mmHg of direct measures for Dinamap but not for Memodiagnostic. CLINICAL SIGNIFICANCE: Both devices failed to meet ACVIM guideline validation. However, Dinamap only failed with regards to correlation. Memodiagnostic failed on several requirements, and based on poor correlation, accuracy and precision, this device cannot be currently recommended for dogs under anaesthesia.

Unsupervised segmentation of the prostate using MR images based on level set with a shape prior.

Prostate cancer is the second leading cause of cancer death in American men. Current prostate MRI can benefit from automated tumor localization to help guide biopsy, radiotherapy and surgical planning. An important step of automated prostate cancer localization is the segmentation of the prostate. In this paper, we propose a fully automatic method for the segmentation of the prostate. We firstly apply a deformable ellipse model to find an ellipse that best fits the prostate shape. Then, this ellipse is used to initiate the level set and constrain the level set evolution with a shape penalty term. Finally, certain post processing methods are applied to refine the prostate boundaries. We apply the proposed method to real diffusion-weighted (DWI) MRI images data to test the performance. Our results show that accurate segmentation can be obtained with the proposed method compared to human readers.

Chronic intervertebral disk herniation associated with fused vertebrae treated by vertebral lateral corpectomy in a cat.

A 10-year-old Domestic Shorthair cat was admitted for chronic ambulatory paraparesis and a spinal malformation. The clinical examination revealed paraparesis accentuated on the left side. Thoracolumbar radiographs revealed a spinal malformation with a narrowed intervertebral space between L1 and L2, and a dorsal fusion at the level of L2-L3 with a common dorsal process. Magnetic resonance imaging (MRI) revealed an intervertebral disk herniation with a ventral compression of the spinal cord at the level of L1/2. A standard vertebral lateral corpectomy with a foraminotomy was performed with a good outcome.

Genome scanning with array CGH delineates regional alterations in mouse islet carcinomas.

Carcinomas that develop in the pancreatic islets of transgenic mice expressing the SV40 T-antigens (Tag) under transcriptional control of the rat insulin II promoter (RIP) progress through well-characterized stages that are similar to aspects of human tumor progression, including hyperplastic growth, increased angiogenesis and reduced apoptosis. The latter two stages have been associated with recurrent loss of heterozygosity (LOH) and reduced genome copy number on chromosomes 9 (LOH9) and 16 (LOH16), aberrations which we believe contribute to these phenotypes. Earlier analyses localized LOH9 to approximately 3 Mb and LOH16 to approximately 30 Mb (both syntenic with human 3q21-q25) but were limited by low throughput and a lack of informative polymorphic markers. Here we show that comparative genomic hybridization to DNA microarrays (array CGH) overcomes these limitations by allowing efficient, genome-wide analyses of relative genome copy number. The CGH arrays used in these experiments carried BACs distributed at 2-20-MB intervals across the mouse genome and at higher density in regions of interest. Using array CGH, we further narrowed the loci for LOH9 and LOH16 and defined new or previously unappreciated recurrent regions of copy-number decrease on chromosomes 6, 8 and 14 (syntenic with human chromosomes 12p11-p13, 16q24.3 and 13q11-q32, respectively) and regions of copy-number increase on chromosomes 2 and 4 (syntenic to human chromosomes 20q13.2 and 1p32-p36, respectively). Our analyses of human genome sequences syntenic to these regions suggest that CYP24, PFDN4, STMN1, CDKN1B, PPP2R3 and FSTL1 are candidate oncogenes or tumor-suppressor genes. We also show that irradiation and genetic background influence the spectrum of aberrations present in these tumors.

DNA polymerase eta undergoes alternative splicing, protects against UV sensitivity and apoptosis, and suppresses Mre11-dependent recombination.

Polymerase eta (pol eta) is a low-fidelity DNA polymerase that is the product of the gene, POLH, associated with the human XP variant disorder in which there is an extremely high level of solar-induced skin carcinogenesis. The complete human genomic sequence spans about 40 kb containing 10 coding exons and a cDNA of 2.14 kb; exon I is untranslated and is 6 kb upstream from the first coding exon. Using bacterial artificial chromosomes (BACs), the gene was mapped to human chromosome band 6p21 and mouse band 17D. The gene is expressed in most tissues, except for very low or undetectable levels in peripheral lymphocytes, fetal spleen, and adult muscle; exon II, however, is frequently spliced out in normal cells and in almost half the transcripts in the testis and fetal liver. Expression of POLH in a multicopy episomal vector proved nonviable, suggesting that overexpression is toxic. Expression from chromosomally integrated linear copies using either an EF1-alpha or CMV promoter was functional, resulting in cell lines with low or high levels of pol eta protein, respectively. Point mutations in the center of the gene and in a C-terminal cysteine and deletion of exon II resulted in inactivation, but addition of a terminal 3 amino acid C-terminal tag, or an N- or C-terminal green fluorescent protein, had no effect on function. A low level of expression of pol eta eliminated hMre11 recombination and partially restored UV survival, but did not prevent UV-induced apoptosis, which required higher levels of expression. Polymerase eta is therefore involved in S-phase checkpoint and signal transduction pathways that lead to arrest in S, apoptosis, and recombination. In normal cells, the predominant mechanism of replication of UV damage involves pol eta-dependent bypass, and Mre11-dependent recombination that acts is a secondary, backup mechanism when cells are severely depleted of pol eta.

Evidence for alternate splicing within the mRNA transcript encoding the DNA damage response kinase ATR.

Proper cellular response to genotoxic insult often requires the activity of one or more members of a family of high-molecular weight protein kinases referred to as phosphatidylinositol-3 kinase (PIK)-like proteins. While catalytic activity is an indispensable part of PIK-like protein function, little is currently known about factors that control their activity and/or functions. This deficiency stems, in large part, from our lack of knowledge concerning functionally significant subdomains within the large non-catalytic domain of these proteins. We have determined that the transcript encoding the PIK-like protein ATR undergoes alternate splicing within the region of the mRNA encoding its non-catalytic domain. This conclusion is based on the sequencing of a human expressed sequence tag clone encoding a portion of the ATR cDNA, and is supported by the results of reverse transcriptase-polymerase chain reaction (RT-PCR) assays conducted on total and polyA+ RNA, as well as sequencing of cloned RT-PCR products. Cloning and sequencing of a segment of human genomic DNA indicated that this event arises from splicing of a single 192 bp exon within the ATR gene. Analysis of several human tissues indicated that alternate ATR transcripts are differentially expressed, suggesting that this region of the ATR protein may be of functional importance.

Comprehensive genome sequence analysis of a breast cancer amplicon.

Gene amplification occurs in most solid tumors and is associated with poor prognosis. Amplification of 20q13.2 is common to several tumor types including breast cancer. The 1 Mb of sequence spanning the 20q13.2 breast cancer amplicon is one of the most exhaustively studied segments of the human genome. These studies have included amplicon mapping by comparative genomic hybridization (CGH), fluorescent in-situ hybridization (FISH), array-CGH, quantitative microsatellite analysis (QUMA), and functional genomic studies. Together these studies revealed a complex amplicon structure suggesting the presence of at least two driver genes in some tumors. One of these, ZNF217, is capable of immortalizing human mammary epithelial cells (HMEC) when overexpressed. In addition, we now report the sequencing of this region in human and mouse, and on quantitative expression studies in tumors. Amplicon localization now is straightforward and the availability of human and mouse genomic sequence facilitates their functional analysis. However, comprehensive annotation of megabase-scale regions requires integration of vast amounts of information. We present a system for integrative analysis and demonstrate its utility on 1.2 Mb of sequence spanning the 20q13.2 breast cancer amplicon and 865 kb of syntenic murine sequence. We integrate tumor genome copy number measurements with exhaustive genome landscape mapping, showing that amplicon boundaries are associated with maxima in repetitive element density and a region of evolutionary instability. This integration of comprehensive sequence annotation, quantitative expression analysis, and tumor amplicon boundaries provide evidence for an additional driver gene prefoldin 4 (PFDN4), coregulated genes, conserved noncoding regions, and associate repetitive elements with regions of genomic instability at this locus.

Improved image quality and computation reduction in 4-D reconstruction of cardiac-gated SPECT images.

Spatiotemporal reconstruction of cardiac-gated SPECT images permits us to obtain valuable information related to cardiac function. However, the task of reconstructing this four-dimensional (4-D) data set is computation intensive. Typically, these studies are reconstructed frame-by-frame: a nonoptimal approach because temporal correlations in the signal are not accounted for. In this work, we show that the compression and signal decorrelation properties of the Karhunen-Loève (KL) transform may be used to greatly simplify the spatiotemporal reconstruction problem. The gated projections are first KL transformed in the temporal direction. This results in a sequence of KL-transformed projection images for which the signal components are uncorrelated along the time axis. As a result, the 4-D reconstruction task is simplified to a series of three-dimensional (3-D) reconstructions in the KL domain. The reconstructed KL components are subsequently inverse KL transformed to obtain the entire spatiotemporal reconstruction set. Our simulation and clinical results indicate that KL processing provides image sequences that are less noisy than are conventional frame-by-frame reconstructions. Additionally, by discarding high-order KL components that are dominated by noise, we can achieve savings in computation time because fewer reconstructions are needed in comparison to conventional frame-by-frame reconstructions.

Iterative linear minimum mean-square-error image restoration from partially known blur.

We address the problem of space-invariant image restoration when the blurring operator is not known exactly, a situation that arises regularly in practice. To account for this uncertainty, we model the point-spread function as the sum of a known deterministic component and an unknown random one. Such an approach has been studied before, but the problem of estimating the parameters of the restoration filter to our knowledge has not been addressed systematically. We propose an approach based on a Gaussian statistical assumption and derive an iterative, expectation-maximization algorithm that simultaneously restores the image and estimates the required filter parameters. We obtain two versions of the algorithm based on two different models for the statistics of the image. The computations are performed in the discrete Fourier transform domain; thus they are computationally efficient even for large images. We examine the convergence properties of the resulting estimators and evaluate their performance experimentally.

Preliminary assessment of extrastriatal dopamine D-2 receptor binding in the rodent and nonhuman primate brains using the high affinity radioligand, 18F-fallypride.

We have identified the value of 18F-fallypride [(S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide], as a dopamine D-2 receptor radiotracer for the study of striatal and extrastriatal receptors. Fallypride exhibits high affinities for D-2 and D-3 subtypes and low affinity for D-4 (3H-spiperone IC50s: D-2 = 0.05 nM [rat striata], D-3 = 0.30 nM [SF9 cell lines, rat recombinant], and D-4 = 240 nM [CHO cell lines, human recombinant]). Biodistribution in the rat brain showed localization of 18F-fallypride in striata and extrastriatal regions such as the frontal cortex, parietal cortex, amygdala, hippocampus, thalamus, and hypothalamus. In vitro autoradiographic studies in sagittal slices of the rat brain showed localization of 18F-fallypride in striatal and several extrastriatal regions, including the medulla. Positron emission tomography (PET) experiments with 18F-fallypride in male rhesus monkeys were carried out in a PET VI scanner. In several PET experiments, apart from the specific binding seen in the striatum, specific binding of 18F-fallypride was also identified in extracellular regions (in a lower brain slice, possibly the thalamus). Specific binding in the extrastriata was, however, significantly lower compared with that observed in the striata of the monkeys (extrastriata/cerebellum = 2, striata/cerebellum = 10). Postmortem analysis of the monkey brain revealed significant 18F-fallypride binding in the striata, whereas binding was also observed in extrastriatal regions such as the thalamus, cortical areas, and brain stem.

Exercise--it's never too late: the strong-for-life program.

OBJECTIVES: This investigation determined whether an in-home resistance training program achieved health benefits in older adults with disabilities. METHODS: A randomized controlled trial compared the effects of assigning 215 older persons to either a home-based resistance exercise training group or a waiting list control group. Assessments were conducted at baseline and at 3 and 6 months following randomization. The program consisted of videotaped exercise routines performed with elastic bands of varying thickness. RESULTS: High rates of exercise adherence were achieved, with 89% of the recommended exercise sessions performed over 6 months. Relative to controls, subjects who participated in the program achieved statistically significant lower extremity strength improvements of 6% to 12%, a 20% improvement in tandem gait, and a 15% to 18% reduction in physical and overall disability at the 6-month follow-up. No adverse health effects were encountered. CONCLUSIONS: These findings provide important evidence that home-based resistance exercise programs designed for older persons with disabilities hold promise as an effective public health strategy.

The human homologue for the Caenorhabditis elegans cul-4 gene is amplified and overexpressed in primary breast cancers.

Amplification is a key mechanism whereby a cancer cell increases the message level of genes that confer a selective advantage when they are overexpressed. In breast cancer, there are many chromosome regions present in multiple copies relative to overall DNA copy number (amplicons), and their target genes are unknown. Using differential display, we have cloned and sequenced the full coding region of a candidate amplicon target gene located on chromosome 13. This candidate is the human homologue of the Caenorhabditis elegans cul-4 gene, cul-4A, a member of the novel cullin gene family, which is involved in cell cycle control of C. elegans. cul-4A was amplified and overexpressed in 3 of 14 breast cancer cell lines analyzed, and it was overexpressed in 8 additional cell lines in which it was not amplified. The latter observation, indicating that its overexpression can occur by mechanisms other than gene amplification, suggests that cul-4A plays a key role in carcinogenesis. Moreover, cul-4A was found to be amplified in 17 of 105 (16%) cases of untreated primary breast cancers, and 14 of 30 cases analyzed (47%) were shown by RNA in situ hybridization to overexpress cul-4A. These results suggest that up-regulation of cul-4A may play an important role in tumor progression.

Spatial relationships in early signaling events of flow-mediated endothelial mechanotransduction.

Blood flow interactions with the vascular endothelium represent a specialized example of mechanical regulation of cell function that has important physiological and pathological cardiovascular consequences. The endothelial monolayer in vivo acts as a signal transduction interface for forces associated with flowing blood (hemodynamic forces) in the acute regulation of artery tone and chronic structural remodeling of arteries, including the pathology of atherosclerosis. Mechanisms related to spatial relationships at the cell surfaces and throughout the cell that influence flow-mediated endothelial mechanotransduction are discussed. In particular, flow-mediated ion channel activation and cytoskeletal dynamics are considered in relation to topographic analyses of the luminal and abluminal surfaces of living endothelial cells.

Image reconstruction for dynamic PET based on low-order approximation and restoration of the sinogram.

Many image-reconstruction methods have been proposed to improve the spatial resolution of positron emission tomography (PET) images and, thus, to produce better quantification. However, these techniques, which are designed for static images, may be inadequate for good reconstruction from dynamic data. We present a simple, but effective, reconstruction approach intended specifically for dynamic studies. First, the level of noise in dynamic PET data is reduced by smoothing along the time axis using a low-order approximation. Next, the denoised sinograms are restored spatially by the method of projections onto convex sets. Finally, images are reconstructed from the restored sinograms by ordinary filtered backprojection. We present experimental results that demonstrate substantial improvements in region-of-interest quantification in actual and simulated dopamine D-2 neuroreceptor-imaging studies of a monkey brain.

Effect of spatial coherence on knife-edge measurements of detector modulation transfer function.

When an image of an edge object is used in the determination of the modulation transfer function of a detector array, the partial coherence of the illumination is often ignored. Although this approximation is valid in some cases, it may not be satisfactory, particularly for the small detector elements characteristic of present-day charge-coupled devices. Here we demonstrate the effect of partial coherence on edge-based modulation transfer function determination for various pixel sizes, degrees of coherence, and f-numbers of the test optics.