Trends influencing the cost of care and patient safety. Decision-making in five key areas can improve clinical and economic performance.
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Biomedical subjects
Publications and source records attributed to Robert Clark.
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Our hypotheses were (1) that plain radiography of the cervical spine in the evaluation of low risk patients with minor blunt trauma is accurate and (2) that computed tomography (CT) of the cervical spine in the evaluation of low risk patients is unnecessary. This study evaluates those hypotheses. We prospectively recorded findings of all patients with blunt trauma who underwent imaging over a period of 70 days. Injury status was determined by review of all radiographic studies obtained on each patient. Chart reviews were performed to determine mechanism of injury and neurological status. Patients were divided into three groups: very low risk, low risk, and high risk. Study end point was fracture. The study included 219 patients. The very low risk group had 107 patients, none of whom had fractures found on CT (projected specificity of plain radiography: 100%). The low risk group contained 78 patients who had no fractures seen on plain radiography or CT (specificity of plain radiography and CT: 100%). The high risk group consisted of 34 patients; 15 had fractures demonstrated on CT. Plain radiography missed one fracture out of 15. In low risk patients, plain radiography is an efficient diagnostic exam with a specificity of 100%. In high risk patients, plain radiography is a good adjunctive screening exam in conjunction with CT scan, with a sensitivity of 93.3% and specificity of 95%.
As the soft copy reading and computer assisted diagnosis (CAD) in mammography become more and more important, the standardization of digital images becomes paramount. Telemammography and telemedicine requires the standardization for image characteristics, such as image resolution, bit-depth and intensity response. Soft copy reading and CAD in mammography are both dependent on the characteristics of the source of the digital data, either direct digital mammography or digitized screen-film mammography. An algorithm developed on images from one database may not perform well as on images from another database (with a different digitization). In this paper, we describe two methods based on a genetic algorithm and a nonlinear algorithm for standardization of digitized and digital mammography. The proposed standardization techniques are based on geometric and intensity transformations that are discovered using a set of calibration images. A set of transformation algorithm is used to search for the best standardization.
BACKGROUND: Because of the recent reclassification of mesenchymal tumors, which was based on a better understanding of the genetics and immunophenotype of gastrointestinal stromal tumors (GISTs), only a limited number of studies have described the radiologic appearance of GISTs. METHODS: This study reviews the imaging characteristics of GISTs, with an emphasis on differentiating benign and malignant tumors using positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI). We reviewed the data from 53 cases of GISTs treated at our institute. The imaging studies from these cases, which were recorded at our institute from January 1998 through June 2003, included PET, CT, and MRI. RESULTS: Of the 53 GIST cases, stomach and small bowel tumors accounted for 80% of the tumors. Malignant lesions were larger and more heterogeneous, had ulcerations, and were PET positive. Peritoneal and liver metastases were most common. CONCLUSIONS: PET, CT, and MRI appear to be useful in differentiating nonmetastasizing from malignant GISTs.
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We have developed a monoclonal antibody (4A7) directed against the C-terminus of the ataxin-2 protein that is involved in the polyglutamine neurodegenerative disorder spinocerebellar ataxia type 2. Comparison with other ataxin-2 antibodies showed that 4A7 specifically recognized ataxin-2. In contrast, a previously reported ataxin-2 antibody (15F6) did not appear to recognize full-length ataxin-2 in our systems. Immunocytochemical and subcellular fractionation studies using 4A7 confirmed previous reports that ataxin-2 is localized to both the cytoplasm and the trans-Golgi network in rat PC12 cells and rat brain tissue. In contrast, 4A7 failed to label the trans-Golgi network in the three primate cell lines examined. Cytoplasmic ataxin-2 was not associated with mitochondria, lysosomes, endoplasmic reticulum, peroxisomes, proteasomes, clathrin-coated pits or vesicles, or F-actin. Ataxin-2 was found to be phosphorylated but not glycosylated, and exhibited an estimated half-life of not less than 21 h. Interestingly, another commercially available ataxin-2 antibody did not detect ataxin-2 localized to the trans-Golgi network. This antibody was also found to immunoprecipitate fewer proteins/protein partners than 4A7. Although cross-reactivity of the 4A7 antibody with other protein(s) cannot be ruled out, it appears likely that the interaction of ataxin-2 with other cell components is dependent on both the host cell type and its subsequent subcellular localization.
In Saccharomyces cerevisiae, splicing of HAC1 mRNA is initiated in response to the accumulation of unfolded proteins in the endoplasmic reticulum by the transmembrane kinase-endoribonuclease Ire1p. Spliced Hac1p (Hac1ip) is a negative regulator of differentiation responses to nitrogen starvation, pseudohyphal growth, and meiosis. Here we show that the RPD3-SIN3 histone deacetylase complex (HDAC), its catalytic activity, recruitment of the HDAC to the promoters of early meiotic genes (EMGs) by Ume6p, and the Ume6p DNA-binding site URS1 in the promoters of EMGs are required for nitrogen-mediated negative regulation of EMGs and meiosis by Hac1ip. Co-immunoprecipitation experiments demonstrated that Hac1ip can interact with the HDAC in vivo. Systematic analysis of double deletion strains revealed that HAC1 is a peripheral component of the HDAC. In summary, nitrogen-induced synthesis of Hac1ip and association of Hac1ip with the HDAC are physiological events in the regulation of EMGs by nutrients. These data also define for the first time a gene class that is under negative control by the UPR, and provide the framework for a novel mechanism through which bZIP proteins repress transcription.
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OBJECTIVE: To analyze the effectiveness of autologous endometrial coculture (AECC) in improving embryo quality and pregnancy rates in 1,030 consecutive cycles of in vitro fertilization-embryo transfer (IVF-ET) utilizing AECC from January 1996 to December 2001. STUDY DESIGN: Embryos from each of 1,030 patients allocated to growth on AECC were analyzed for outcome. All patients had previously undergone failed IVF cycles. During a luteal phase biopsy (5-12 days after the luteinizing hormone surge) performed prior to the treatment cycle, glandular (G) and stromal (S) endometrial cells were isolated by enzymatic digestion and separated based on differential sedimentation rates. These cells were cryopreserved, then plated as a 50%/50% combination of G and S cells prior to embryo exposure. The conditioned medium was changed every 2 days. Embryos were randomly grown on endometrial coculture (ECC) or conventional media if > 6 oocytes were normally fertilized. Otherwise, all embryos were grown on AECC. RESULTS: The patients' mean age was 36.9 (+/-3.1) years. The patients had on average a history of 3.1 (+/- 1.7) failed prior attempts. When comparing a previous cycle (same institution only), the cleaved embryos on day 3 were of an improved quality (6.8+/-1.2 vs. 5.5+/-1.0 blastomeres and 14.6% +/- 9.3 vs. 27.2% +/- 9.8 fragmentation, P <.05). Twenty-two (2.13%) patients did not undergo ET secondary to poor embryonic development. Overall positive and clinical pregnancy rates of 49.8% and 41.5% were noted, respectively. Age remained the most important predictor of outcome. CONCLUSION: We demonstrated a significant improvement in embryo quality with ECC. We also demonstrated that patients with a poor prognosis secondary to prior IVF failures can have a good outcome when utilizing AECC.
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The unfolded protein response (UPR) is a signalling pathway leading to transcriptional activation of genes that protect cells from accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER). In yeast, the only known ER stress signalling pathway originates at the type I transmembrane protein kinase/endoribonuclease Ire1p. Ire1p regulates synthesis of the basic leucine-zipper (bZIP)-containing transcription factor Hac1p by controlling splicing of HAC1 mRNA. Only spliced HAC1 mRNA (HAC1i) is translated, and Hac1ip activates transcription of genes that contain a conserved UPR element (UPRE) in their promoters. Here, we demonstrate that in addition to this well-understood ER stress signalling pathway, a second, IRE1, HAC1 and UPRE-independent mechanism for transcriptional activation upon ER stress, exists in yeast. A genetic screen identified recessive SIN4 alleles as suppressors of a defective UPR in ire1 Delta strains. Elevation of basal transcription in sin4 strains or by tethering the RNA polymerase II holoenzyme with LexAp-holoenzyme component fusion proteins to a promoter allowed for activation of the promoter by ER stress in an IRE1, HAC1 and UPRE-independent manner. We propose that this novel second ER-to-nucleus signal transduction pathway culminates in core promoter activation (CPA) through stimulation of RNA polymerase II holoenzyme activity. Core promoter activation was observed upon diverse cellular stresses, suggesting it represents a primordial stress-induced gene activation mechanism.
We present results of investigations of the clinical significance of variations in the value of the 4-mm-collimator output factor, OF(4/18). Changes in treatment volume, dose-volume histograms (DVHs), and isodose distributions were studied, by varying OF(4/18) up to 20%. The variations were performed on a sample of clinical patient treatment plans for which the 4 mm collimator was used. Although smaller effects are noted for the prescription isodose line, greater dosimetric changes occur for higher dose regions within the target.
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STUDY OBJECTIVE: To appraise the potential cost-effectiveness of lung cancer screening with CT. STUDY DESIGN: Incremental cost-effectiveness ratios are estimated for two hypothetical cohorts followed up over time. One cohort was screened over the first 5 years of the study period; the other cohort received usual care. Cost streams are projected for each cohort under alternative sets of parameters/ assumptions and from the perspective of national payer groups. Cohort cost differentials arise as a result of screening and variations in stage-specific treatment. Cohort life expectancies are also projected, and they too differ as a consequence of variations in the stage distribution at diagnosis. The ratios of these cost and life-expectancy differences are used to judge the expected economic value of screening. RESULTS: Results are analyzed for a "worst-case" scenario, ie, with the highest cost and lowest yield assumptions. Under these conditions, screening with CT costs approximately $48,000 per life-year gained, if screening results in 50% of lung cancers detected at localized stage. Smaller proportions of cancer detected at a localized stage result in higher cost-effectiveness ratios, and vice versa. CONCLUSION: If screening for lung cancer is effective, it is likely to be cost-effective if the screening process can detect > 50% of cancers at localized stage.
Hemorrhage associated with duodenal varices is an uncommon but often fatal manifestation of portal hypertension. We report a case of duodenal varices, review the literature, and present a new treatment modality. A 63-year-old man presented with hematemesis and hematochezia. An upper gastrointestinal endoscopy revealed hemorrhage from the duodenal varices that was initially controlled with injections of epinephrine. However, this was only partially successful, as the patient had repeated episodes of bleeding that was not amenable to injection sclerotherapy. The patient was taken emergently to the operating room after endoscopy failed to control the hemorrhage. The bleeding was controlled with simple oversewing of the duodenal varices through a duodenotomy. Three years later the patient remains symptom free. We propose that simple oversewing of duodenal variceal veins combined with a beta-blocker is an effective treatment for duodenal variceal hemorrhage.