Information Services Publications and Presentations Copyright (c) 2013 University of Massachusetts Medical School All rights reserved. http://escholarship.umassmed.edu/infoservices Recent documents in Information Services Publications and Presentations en-us Wed, 13 Feb 2013 16:58:32 PST 3600 Determination of cystic duct patency using hepatobiliary MRI with gadoxetate disodium: Is T1 precontrast imaging necessary http://escholarship.umassmed.edu/infoservices/95 http://escholarship.umassmed.edu/infoservices/95 Fri, 13 Jul 2012 08:12:27 PDT PURPOSE: To determine the need for precontrast T1-weighted imaging in determining cystic duct patency using hepatobiliary phase imaging with gadoxetate disodium-enhanced magnetic resonance imaging (MRI).

MATERIALS AND METHODS: MRI exams using gadoxetate disodium from October 4, 2008 to April 14, 2010 were reviewed in a retrospective fashion. Two reviewers independently reviewed only the 20-minute T1-weighted delayed postcontrast images to determine the presence of excreted contrast in the gallbladder lumen. Contrast was deemed present if hyperintense signal material was seen in the antidependent portion of the gallbladder lumen. The actual presence of contrast in the gallbladder was determined by directly comparing the pre- and postcontrast T1-weighted images using consensus review.

RESULTS: In all, 187 cases were included. Three (1.6%) were deemed indeterminate due to complete homogeneous opacification of the gallbladder. All three cases were identified as indeterminate by both reviewers. Of the remaining 184 cases, 136 filled (74%) and 48 did not fill (26%). Both reviewers correctly identified 136/136 cases of gallbladder filling. Reviewer A identified 47/48 cases of nonfilling and reviewer B identified 46/48 cases of nonfilling. Sensitivity and specificity were 100% and 98% for reviewer A and 100% and 96% for reviewer B, respectively.

CONCLUSION: The presence of excreted contrast in the gallbladder lumen can be determined using gadoxetate disodium-enhanced MRI without precontrast T1-weighted imaging.

J. Magn. Reson. Imaging 2011;35:601-606. (c) 2011 Wiley Periodicals, Inc.

]]> Michael T. Corwin et al. Bile Duct Diseases Contrast Media Cystic Duct Gadolinium DTPA Magnetic Resonance Imaging Disruption of IFT Complex A Causes Cystic Kidneys without Mitotic Spindle Misorientation http://escholarship.umassmed.edu/infoservices/94 http://escholarship.umassmed.edu/infoservices/94 Fri, 13 Jul 2012 08:12:24 PDT Intraflagellar transport (IFT) complexes A and B build and maintain primary cilia. In the mouse, kidney-specific or hypomorphic mutant alleles of IFT complex B genes cause polycystic kidneys, but the influence of IFT complex A proteins on renal development is not well understood. In the present study, we found that HoxB7-Cre-driven deletion of the complex A gene Ift140 from collecting ducts disrupted, but did not completely prevent, cilia assembly. Mutant kidneys developed collecting duct cysts by postnatal day 5, with rapid cystic expansion and renal dysfunction by day 15 and little remaining parenchymal tissue by day 20. In contrast to many models of polycystic kidney disease, precystic Ift140-deleted collecting ducts showed normal centrosomal positioning and no misorientation of the mitotic spindle axis, suggesting that disruption of oriented cell division is not a prerequisite to cyst formation in these kidneys. Precystic collecting ducts had an increased mitotic index, suggesting that cell proliferation may drive cyst expansion even with normal orientation of the mitotic spindle. In addition, we observed significant increases in expression of canonical Wnt pathway genes and mediators of Hedgehog and tissue fibrosis in highly cystic, but not precystic, kidneys. Taken together, these studies indicate that loss of Ift140 causes pronounced renal cystic disease and suggest that abnormalities in several different pathways may influence cyst progression.

]]> Julie A. Jonassen et al. Kidney Diseases, Cystic Prevention of Alzheimer's disease in high risk groups: statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein E epsilon 4 http://escholarship.umassmed.edu/infoservices/93 http://escholarship.umassmed.edu/infoservices/93 Tue, 02 Aug 2011 07:43:57 PDT Because cerebrospinal fluid (CSF) abnormalities in presymptomatic subjects with PSEN1 (presenilin 1) mutations may be observed 4 to 12 years prior to the estimated age at onset, it is possible to test putative therapies on the CSF analytes that correlate with neurodegeneration during this presymptomatic window of clinical opportunity. It is also possible to test the same therapy on a comparison group with increased risk status conferred by both hyperlipidemia and heterozygosity for apolipoprotein Eε4. To our knowledge, the only putative therapy thus far tested in such a common design has been statin therapy. The results of these tests show increases in soluble amyloid precursor protein (sAPP)α correlating with statin-induced decreases in serum cholesterol levels in the non-PSEN1 subjects. This result could be one functional correlate for part of the substantial risk reduction for late onset Alzheimer's disease recently reported in the Rotterdam study, a large, long-term prospective statin trial. Statin therapy significantly decreased both sAPPα and sAPPβ in presymptomatic PSEN1 subjects. Initially, elevated phospho-tau levels in PSEN1 subjects did not further increase during the 2 to 3 years of statin therapy, possibly indicative of a prophylactic effect. These results suggest that large and longer term trials of statin therapy correlating changes in CSF biomarker levels with clinical course may be warranted in both presymptomatic PSEN1 and non-PSEN1 subjects.

]]> Daniel A. Pollen et al. Cerebrospinal Fluid Presenilin-1 Alzheimer Disease Apolipoprotein E4 Hydroxymethylglutaryl-CoA Reductase Inhibitors A preclinical 188Re tumor therapeutic investigation using MORF/cMORF pretargeting and an antiTAG-72 antibody CC49 http://escholarship.umassmed.edu/infoservices/92 http://escholarship.umassmed.edu/infoservices/92 Tue, 02 Aug 2011 07:43:53 PDT The utility of MORF/cMORF pretargeting for the radiotherapy of cancer requires further validation in tumored mice before clinical trials. We now report on a therapeutic study in mice pretargeted with MORF-CC49 (an anti-TAG-72 antibody CC49 conjugated with MORF, a phosphorodiamidate morpholino oligomer) and then targeted by 188Re-cMORF (a 188Re labeled complementary MORF). Before the dose-escalating therapeutic study, a pretargeting study in LS174T tumored mice was performed at tracer levels. By both necropsy and imaging, the tracer study showed that the whole body radioactivity was largely restricted to tumor in the mice pretargeted 48 h earlier with MORF-CC49 and the tumor radioactivity was retained over 90 h. After decay correction, a best-fit to the biodistribution provided the areas under the radioactivity curves (AUCs) used for the radiation dose estimates. The tumor to normal organ AUC ratios in all cases were greater than unity and ranged from 3 (kidneys) to 48 (muscle). Tumor growth was inhibited in the therapy study. At the highest 188Re dose of 1.40 mCi, a complete but temporary tumor remission was evident in 3 out of the 5 animals. Histological examination of tissues from these animals showed no evidence of cytotoxicity to normal tissues but obvious radiation damage to tumor. In conclusion, effective radiotherapy was achieved in a mouse model by MORF/cMORF pretargeting using 188Re as the therapeutic radionuclide and CC49 as the pretargeting antibody.

]]> Guozheng Liu et al. Colonic Neoplasms Radioisotopes Radiopharmaceuticals Xenograft Model Antitumor Assays Response to Comment on "Reassessment of the Role of Mut S Homolog 5 in Ig Class Switch Recombination Shows Lack of Involvement in cis- and trans-Switching" http://escholarship.umassmed.edu/infoservices/91 http://escholarship.umassmed.edu/infoservices/91 Thu, 25 Mar 2010 09:00:39 PDT Response to: Reassessment of the role of Mut S homolog 5 in Ig class switch recombination shows lack of involvement in cis- and trans-switching. Guikema JE, Schrader CE, Leus NG, Ucher A, Linehan EK, Werling U, Edelmann W, Stavnezer J. J Immunol. 2008 Dec 15;181(12):8450-9.PMID: 19050263.

]]> Jeroen E. J. Guikema et al. Cell Cycle Proteins DNA-Binding Proteins Immunoglobulin Class Switching Recombination, Genetic Inhibition of neutrophil apoptosis after severe trauma is NFkappabeta dependent http://escholarship.umassmed.edu/infoservices/90 http://escholarship.umassmed.edu/infoservices/90 Thu, 11 Mar 2010 10:37:07 PST BACKGROUND: Systemic inflammation may inhibit neutrophil (PMN) apoptosis and promote multiple organ dysfunction syndrome. We hypothesize that severe trauma causes dysregulation of PMN apoptosis.

METHODS: Neutrophils were isolated from trauma patients (24-72 hours after injury; n = 16) and controls (healthy volunteers) and incubated for 18 hours. In separate experiments, control cells were treated +/- the nuclear factor kappa beta (NFkappabeta) inhibitor pyrrolidinithiocarbamate then incubated with 25% patient or control plasma. Apoptosis was quantified by enzyme-linked immunosorbent assay for histone-associated DNA and annexin V fluorescence-activated cell sorter. NFkappabeta activation was determined by Western blot for phosphorylated I kappabeta.

RESULTS: Apoptosis was inhibited in trauma patient PMN. Neutrophil apoptosis correlated with multiple organ dysfunction syndrome score, Acute Physiology and Chronic Health Evaluation II, and platelet count. Patient plasma inhibited apoptosis and induced phosphorylation of I kappabeta in control cells. Inhibition of PMN apoptosis by patient plasma was blocked by pretreatment with pyrrolidinithiocarbamate.

CONCLUSION: NFkappabeta-dependent inhibition of neutrophil apoptosis occurs after trauma. Early inhibition of PMN apoptosis is dependent on the magnitude of injury.

]]> Brian Nolan et al. Apoptosis Cells, Cultured Enzyme-Linked Immunosorbent Assay Histones Humans Multiple Organ Failure NF-kappa B Neutrophils Phosphorylation Pyrrolidines Thiocarbamates Wounds and Injuries Interleukin 18 binding protein (IL18-BP) inhibits neointimal hyperplasia after balloon injury in an atherosclerotic rabbit model http://escholarship.umassmed.edu/infoservices/89 http://escholarship.umassmed.edu/infoservices/89 Thu, 11 Mar 2010 10:37:05 PST OBJECTIVES: Interleukin 18 (IL18) is an interferon (IFN)-gamma-inducing factor and a proinflammatory and proatherogenic cytokine. IL18 binding protein (IL18-BP) functions as an IL18 inhibitor. This study was designed to investigate whether systemic administration of IL18-BP could inhibit neointimal hyperplasia and arterial lipid deposition.

METHODS: New Zealand white, male rabbits were fed with a 21% fat, 0.15% cholesterol diet. The left superficial femoral artery (SFA) was de-endotheliazed with a 2F arterial embolectomy catheter. IL18-BP (5 microg, 10 microg, or 25 microg), or 0.9% saline (control) was administered by i.v. bolus during surgery. Rabbits were followed-up at 2 and 4 weeks. Intima-media (I/M) and lumen-whole artery (L/A) area ratios, and luminal areas were measured. Serum lipid levels, liver enzymes, and kidney function were evaluated. Inflammatory cells were quantified and further verified with immunohistofluorescence staining. The extent of lipid deposition in the artery wall was quantified with Oil Red O (ORO) staining employing Zeiss AxioVision 4.6.3. Image analysis software. Lipid laden cells including macrophages were evaluated by transmission electron microscopy (TEM).

RESULTS: Intravenous IL18-BP 5 microg, 10 microg, and 25 microg significantly reduced I/M ratios compared with the control group at both 2 and 4 weeks. There was no significant difference between the 5 microg and 10 microg dose groups. However, at 10 microg, IL18-BP significantly increased L/A ratio more than either the 5 microg IL18-BP or control groups. The high fat diet caused significant elevation of serum lipids at 4 and 6 weeks. IL18-BP had no effect on blood lipid levels. Lipid deposit in the thoracic aorta of the control group at 6 weeks was more than at 4 weeks (P = .025). Administration of IL18-BP inhibited the lipid deposition at 4 weeks (not significant) and 6 weeks (P = .012 to .008) compared with its control group. Lipid laden macrophages (foam cells), as well as endothelial cells and smooth muscle cells were seen in the descending thoracic aorta after 6 weeks of a high fat diet by ORO, immunohistofluorescence staining, and TEM. The lipid laden cells were not seen in either of IL18-BP groups. IL18-BP 10 microg significantly inhibited mono/macro adherence and infiltration in the SFA after balloon-injury at 2 weeks after surgery.

CONCLUSION: A single intravenous dose of IL18-BP significantly decreased arterial neointimal hyperplasia, improved lumen to artery ratio after balloon-injury and also prevented arteriosclerosis progression.

CLINICAL RELEVANCE: A single intravenous dose of IL18BP decreased neointimal hyperplasia and improved arterial L/A ratios in an atherosclerotic balloon-injury animal model. These preliminary results suggest that IL18BP may be a promising molecular approach to inhibit neointimal hyperplasia and arteriosclerosis progression following coronary and peripheral angioplasty.

]]> Jian-ming Li et al. Angioplasty, Balloon Animals Atherosclerosis Dietary Fats Disease Models, Animal Disease Progression Dose-Response Relationship, Drug Femoral Artery Hyperplasia Inflammation Injections, Intravenous Intercellular Signaling Peptides and Proteins Kidney Function Tests Lipid Metabolism Lipids Liver Function Tests Male Mice Rabbits Recombinant Proteins Time Factors Tunica Intima Tunica Media Cell polarity protein Lgl2 is lost or aberrantly localized in gastric dysplasia and adenocarcinoma: an immunohistochemical study http://escholarship.umassmed.edu/infoservices/88 http://escholarship.umassmed.edu/infoservices/88 Thu, 11 Mar 2010 10:37:03 PST The diagnosis of gastric epithelial dysplasia, a precursor lesion of gastric adenocarcinoma, is hindered by interobserver variability and by its resemblance to regenerative changes. Loss of cell polarity, a histological feature of gastric epithelial dysplasia, may be difficult to ascertain, especially in the setting of inflammation or injury. A biomarker of cell polarity could be useful in diagnosis of dysplasia, but has not been reported. The Lethal giant larvae (lgl) gene controls apical-basal polarity of epithelial cells in Drosophila, and has properties of a tumor-suppressor gene. Two homologs, lgl1 and lgl2, are present in mammals and lgl2 mRNA is highly expressed in the stomach. The goal of our study was to test the hypothesis that Lgl2 protein expression and/or localization are disrupted in gastric epithelial dysplasia and adenocarcinoma. Routinely processed pathology specimens including 94 benign mucosae of digestive organs, in addition to 36 reactive gastropathy, 57 gastric epithelial dysplasia, and 77 gastric adenocarcinomas, were immunostained for Lgl2 protein. All normal, reactive, and chronically inflamed gastric epithelia showed basolateral Lgl2 staining. Normal esophageal, duodenal, colonic, biliary, and pancreatic duct mucosae, as well as gastric intestinal metaplasia, did not express Lgl2. All but one case each of gastric epithelial dysplasia and adenocarcinoma showed either complete loss of anti-Lgl2 immunoreactivity or diffuse, mostly weak, cytoplasmic staining. Complete loss of immunoreactivity was significantly more often observed in diffuse-type than in intestinal-type adenocarcinomas (79 vs 48%, respectively). Our data suggest that Lgl2 expression is either aberrantly localized or lost in gastric epithelial dysplasia and adenocarcinoma, whereas it is maintained in reactive gastric mucosa. We propose that Lgl2 may be a potential marker to rule out gastric epithelial dysplasia and adenocarcinoma in diagnostic specimens. However, the consistently negative anti-Lgl2 immunoreactivity seen in intestinal metaplasia does not allow differentiation of dysplasia from intestinal metaplasia with reactive change.

]]> Mikhail Lisovsky et al. Adenocarcinoma Adenoma Adolescent Adult Aged Aged, 80 and over Cell Polarity Cytoskeletal Proteins Female Fluorescent Antibody Technique, Direct Gastric Mucosa Humans Immunoenzyme Techniques Male Middle Aged Precancerous Conditions Stomach Neoplasms Tumor Markers, Biological Young Adult Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia http://escholarship.umassmed.edu/infoservices/87 http://escholarship.umassmed.edu/infoservices/87 Thu, 11 Mar 2010 10:37:01 PST BACKGROUND: Prefrontal deficits in gamma-aminobutyric acid (GABA)ergic gene expression, including neuropeptide Y (NPY), somatostatin (SST), and parvalbumin (PV) messenger RNAs (mRNAs), have been reported for multiple schizophrenia cohorts. Preclinical models suggest that a subset of these GABAergic markers (NPY/SST) is regulated by brain-derived neurotrophic factor (BDNF), which in turn is under the inhibitory influence of small noncoding RNAs. However, it remains unclear if these mechanisms are important determinants for dysregulated NPY and SST expression in prefrontal cortex (PFC) of subjects with schizophrenia.

METHODS: Using a postmortem case-control design, the association between BDNF protein, NPY/SST/PV mRNAs, and two BDNF-regulating microRNAs (miR-195 and miR-30a-5p) was determined in samples from the PFC of 20 schizophrenia and 20 control subjects. Complementary studies were conducted in cerebral cortex of mice subjected to antipsychotic treatment or a brain-specific ablation of the Bdnf gene.

RESULTS: Subjects with schizophrenia showed deficits in NPY and PV mRNAs. Within-pair differences in BDNF protein levels showed strong positive correlations with NPY and SST and a robust inverse association with miR-195 levels, which in turn were not affected by antipsychotic treatment or genetic ablation of Bdnf.

CONCLUSIONS: Taken together, these results suggest that prefrontal deficits in a subset of GABAergic mRNAs, including NPY, are dependent on the regional supply of BDNF, which in turn is fine-tuned through a microRNA (miRNA)-mediated mechanism.

]]> Nikolaos Mellios et al. Adult Aged Aged, 80 and over Animals Brain-Derived Neurotrophic Factor Case-Control Studies Chromatin Gene Expression Regulation Genotype Humans Immunoassay Immunoprecipitation Male Mice Mice, Inbred C57BL Mice, Knockout MicroRNAs Middle Aged Neuropeptide Y Parvalbumins Prefrontal Cortex RNA Schizophrenia Somatostatin Young Adult gamma-Aminobutyric Acid Long-term statin therapy and CSF cholesterol levels: implications for Alzheimer's disease http://escholarship.umassmed.edu/infoservices/86 http://escholarship.umassmed.edu/infoservices/86 Thu, 11 Mar 2010 10:37:00 PST BACKGROUND/AIMS: It is not yet established whether statins (lipophilic or hydrophilic) reduce the risk of Alzheimer's disease and, if so, by differentially modifying brain lipid levels. Our aim was to assess changes in brain cholesterol metabolism as reflected in the cerebrospinal fluid (CSF) before and after treatment with either atorvastatin or simvastatin.

METHODS: We carried out a longitudinal analysis of CSF cholesterol, lathosterol and 24(S)-hydroxycholesterol before and after treatment with maximum doses of statins in 10 asymptomatic subjects, 8 of whom were heterozygous for apolipoprotein E epsilon4, and in 6 presymptomatic PS1 subjects.

RESULTS: Statins initially reduced CSF lathosterol cholesterol and 24(S)-hydroxycholesterol in both PS1 and non-PS1 subjects reaching a nadir at 6-7 months, followed by a return to baseline at 15 months with an overshoot at 2 years, tending to return to baseline thereafter.

CONCLUSIONS: Possible long-term protective effects of statins are not likely largely related to the temporally-dependent biphasic effects of statin therapy upon the magnitude and direction of changes in CSF lipid levels and their subsequent return to baseline levels.

]]> Barbara A. Evans et al. Adult Aged Alzheimer Disease Apolipoproteins E Cholesterol Female Heptanoic Acids Heterozygote Humans Hydroxycholesterols Hydroxymethylglutaryl-CoA Reductase Inhibitors Male Middle Aged Mutation Pilot Projects Presenilin-1 Pyrroles Simvastatin Ammonia and carbon dioxide concentrations in disposable and reusable static mouse cages http://escholarship.umassmed.edu/infoservices/85 http://escholarship.umassmed.edu/infoservices/85 Thu, 11 Mar 2010 10:36:59 PST The value of a static mouse cage is partially determined by the cage's ability to dissipate carbon dioxide and ammonia. The authors compared the concentrations of ammonia and carbon dioxide produced by mice housed in two types of static isolator cages: a newly introduced disposable cage and a conventional reusable cage. Female mice were housed in three disposable and three reusable cages (n = 5 per cage). After 7 d, groups that were housed in disposable cages were rehoused in fresh reusable cages and vice versa. Intracage carbon dioxide, ammonia, temperature and relative humidity were measured daily. Overall, there were no significant differences in carbon dioxide or ammonia concentrations between the cage types. Within 30 min of placing mice in cages, carbon dioxide concentrations rose to more than 10,000 ppm in both cage types and rarely dropped below 8,000 ppm during both phases of the study. Ammonia concentrations rose slowly until day 4 and then began to rise rapidly. The maximum average ammonia concentration was 710 ppm. There was a highly significant relationship between increasing levels of humidity and ammonia production in the disposable cages (r = 0.88). For the reusable cages, the correlation was not as strong (r = 0.68). Both cage types were similar in their ability to dissipate carbon dioxide and ammonia. The suggested frequency of cage changing can only be estimated; on the basis of existing literature, it seems prudent to change cages when the ammonia concentration reaches 50 ppm.

]]> Jerald Silverman et al. Ammonia Animals *Animals, Laboratory Carbon Dioxide Disposable Equipment Female Housing, Animal Humidity Mice Mice, Inbred ICR Temperature MDCT of 220 consecutive patients with suspected acute pulmonary embolism: incidence of pulmonary embolism and of other acute or non-acute thoracic findings http://escholarship.umassmed.edu/infoservices/84 http://escholarship.umassmed.edu/infoservices/84 Thu, 11 Mar 2010 10:36:57 PST PURPOSE: This study was undertaken to evaluate the incidence of pulmonary embolism (PE) and other clinically relevant thoracic findings discovered on contrast-enhanced multidetector computed tomography (MDCT) examination in patients with a suspicion of acute PE.

MATERIALS AND METHODS: We retrospectively reviewed 220 reports of 40-row MDCT exams in consecutive patients (101 men, 119 women; mean age 55 years+/-18) suspected for acute PE. Presenting symptoms and risk factors were recorded. Image quality and incidence of PE and other clinically relevant thoracic findings were evaluated.

RESULTS: MDCT were diagnostic in 96.8% of patients. Nineteen patients (8.6%) were positive for PE. Signs and symptoms were present in 82.7% (182) and risk factors in 38.2% (84) of the population. Clinically relevant thoracic findings were detected in 45.9% (101) of the patients. Ten patients had PE and other thoracic findings. Half of the patients (110) had neither PE nor other clinically relevant thoracic findings.

CONCLUSIONS: Chest MDCT, with an excellent overall image quality, provided an explanation for the clinical presentation in about 50% of emergency department patients studied and was useful in detecting PE and other thoracic diseases with symptoms mimicking PE. However, half of the exams were negative.

]]> Silvia Tresoldi et al. Adolescent Adult Aged Aged, 80 and over Female Humans Incidence Italy Lung Diseases Male Middle Aged Predictive Value of Tests Pulmonary Embolism Radiographic Image Enhancement Retrospective Studies Sensitivity and Specificity Tomography, Spiral Computed Statins differentially affect amyloid precursor protein metabolism in presymptomatic PS1 and non-PS1 subjects http://escholarship.umassmed.edu/infoservices/83 http://escholarship.umassmed.edu/infoservices/83 Thu, 11 Mar 2010 10:36:56 PST Douglas A. Hinerfeld et al. Adult Aged Alzheimer Disease Amyloid beta-Protein Amyloid beta-Protein Precursor Apolipoprotein E4 Female Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors Male Middle Aged Mutation Peptide Fragments Presenilin-1 Time Factors Midline anterior repair alone vs anterior repair plus vaginal paravaginal repair: a comparison of anatomic and quality of life outcomes http://escholarship.umassmed.edu/infoservices/82 http://escholarship.umassmed.edu/infoservices/82 Thu, 11 Mar 2010 10:36:55 PST Our aim was to study the anatomic recurrence rates and quality of life outcomes of patients who had undergone either anterior colporrhaphy (AC) or anterior colporrhaphy and vaginal paravaginal repair (AC + VPVR) as part of surgery for pelvic organ prolapse. Chart reviews were used to identify anatomic prolapse recurrence. Phone interviews assessed quality of life outcomes [Urogenital Distress Inventory (UDI) and the Incontinence Impact Questionnaire (IIQ)] outcomes. There was a trend towards longer time to anatomic recurrence (any compartment > or =grade 2) in the AC group compared with the AC + VPVR group (median 24 vs 13 months, p=0.069). If only patients who had undergone previous surgery were compared, time to anatomic recurrence appeared significantly longer in the AC group (median 41 vs 12 months, p=0.022). There were 55% of women in the AC group and 46% of women in the AC + VPVR group who reported significant bladder or bulge symptoms based on responses to the phone-administered UDI and IIQ (p=0.89). Our retrospective study did not suggest that adding VPVR was superior in terms of anatomic or quality of life outcomes. Prospective assessment of the role of VPVR in the treatment of pelvic organ prolapse is needed.

]]> Abraham N. Morse et al. Aged Female Gynecologic Surgical Procedures Humans Middle Aged Parity Pregnancy *Quality of Life Recurrence Retrospective Studies Treatment Outcome Uterine Prolapse Vagina Ammonia and carbon dioxide concentrations in disposable and reusable ventilated mouse cages. http://escholarship.umassmed.edu/infoservices/81 http://escholarship.umassmed.edu/infoservices/81 Mon, 09 Mar 2009 13:39:34 PDT This study compares resuable and disposable individually ventilated mouse cages in terms of the formation of intracage CO2 and NH3. Crl:CD-1(ICR) female mice were placed in either disposable or reusable ventilated cages in a positive pressure animal rack. Intracage CO2 and NH3 were measured once daily for 9 d; temperature and relative humidity were monitored for the first 7 d. Results indicated higher CO2 levels in the rear of the disposable cages and in the front of the reusable cages. This pattern corresponded to where the mice tended to congregate. However, CO2 concentrations did not differ significantly between the 2 cage types. Average CO2 levels in both cage types never exceeded approximately 3000 ppm. Intracage NH3 began to rise in the reusable cages on day 4, reached approximately 50 ppm by day 5 and by day 9 was greater than 150 ppm at the cages' rear sampling port while remaining at approximately 70 ppm at the front sampling port. Intracage NH3 levels in the disposable cages remained less than or equal to 3.2 ppm. Intracage temperature and relative humidity were approximately the same in both cage types. We concluded that the disposable ventilated cage performed satisfactorily under the conditions of the study.

]]> Jerald Silverman et al. Air Pollutants, Occupational Ammonia Animals Animals, Laboratory Carbon Dioxide Disposable Equipment Female Housing, Animal Mice Mice, Inbred Strains Ventilation Comparison of tomosynthesis methods used with digital mammography http://escholarship.umassmed.edu/infoservices/80 http://escholarship.umassmed.edu/infoservices/80 Wed, 21 May 2008 13:27:30 PDT RATIONALE AND OBJECTIVES: The authors performed this study to investigate the potential applicability of tomosynthesis to digital mammography. Four methods of tomosynthesis-tuned aperture computed tomography (TACT)-backprojection, TACT-iterative restoration, iterative reconstruction with expectation maximization, and Bayesian smoothing-were compared to planar mammography and analyzed in terms of their contrast-detail characteristics. Specific comparisons between the tomosynthesis methods were not attempted in this study.

MATERIALS AND METHODS: A full-field, amorphous, silicon-based, flat-panel digital mammographic system was used to obtain planar and tomosynthesis projection images. A composite tomosynthesis phantom with a centrally located contrast-detail insert was used as the object of interest. The total exposure for multiple views with tomosynthesis was always equal to or less than that for the planar technique. Algorithms were used to reconstruct the object from the acquired projections.

RESULTS: Threshold contrast characteristics with all tomosynthesis reconstruction methods were significantly better than those with planar mammography, even when planar mammography was performed at more than twice the exposure level. Reduction of out-of-plane structural components was observed in all the tomosynthesis methods analyzed.

CONCLUSION: The contrast-detail trends of all the tomosynthesis methods analyzed in this study were better than those of planar mammography. Further optimization of the algorithms could lead to better image reconstruction, which would improve visualization of valuable diagnostic information.

]]> Sankararaman Suryanarayanan et al. Breast Neoplasms Mammography Phantoms, Imaging *Radiographic Image Enhancement *Signal Processing, Computer-Assisted *Tomography, X-Ray Computed Quantitative ultrasound: an indicator of osteoporosis in perimenopausal women http://escholarship.umassmed.edu/infoservices/79 http://escholarship.umassmed.edu/infoservices/79 Wed, 21 May 2008 13:27:27 PDT The key to effective treatment of osteoporosis is early detection; however, the disease in perimenopausal women is frequently undiagnosed. To assess the utility of quantitative ultrasound (QUS) at the calcaneus in perimenopausal women, broadband ultrasound attenuation (BUA); speed of sound (SOS); quantitative ultra-sound index (QUI), an algorithm of BUA and SOS; and bone mineral density by dual X-ray absorptiometry (DXA) of the posteroanteiror spine, femoral neck, and total hip were measured in 420 women (ages 45-55 yr). Thirty (7.1%) of the women were found to be osteoporotic by DXA. All QUS measurements were predictors of osteoporosis. QUS values did not differ between postmenopausal women on estrogen replacement therapy (ERT) and those not on ERT. There were no differences among BUA, SOS, and QUI in the area under the receiver operating characteristic curves for predicting osteoporotic vs nonosteoporotic cases. At a QUI of 89, ultrasound had an 80% sensitivity for the diagnosis of osteoporosis, but only a 74% specificity. The use of QUS in perimenopausal women will facilitate the identification of women with osteoporosis. However, the high false-positive rate (26%) limits the utility of QUS as the sole diagnostic technique on which to base therapeutic decisions. Nevertheless, low QUS measurements may provide a means for targeting those women who would benefit most from more extensive evaluation (e. g., DXA).

]]> James G. Nairus et al. Bone Density Calcaneus Diagnosis, Differential Female Femur Neck Hip Joint Humans Middle Aged Osteoporosis, Postmenopausal Premenopause Sensitivity and Specificity Evaluation of linear and nonlinear tomosynthetic reconstruction methods in digital mammography http://escholarship.umassmed.edu/infoservices/78 http://escholarship.umassmed.edu/infoservices/78 Wed, 21 May 2008 13:27:24 PDT RATIONALE AND OBJECTIVES: The purpose of this study was to comparatively evaluate digital planar mammography and both linear and nonlinear tomosynthetic reconstruction methods.

MATERIALS AND METHODS: A "disk" (ie, target) identification study was conducted to compare planar and reconstruction methods. Projective data using a composite phantom with circular disks were acquired in both planar and tomographic modes by using a full-field, digital mammographic system. Two-dimensional projections were reconstructed with both linear (ie, backprojection) and nonlinear (ie, maximization and minimization) tuned-aperture computed tomographic (TACT) methods to produce three-dimensional data sets. Four board-certified radiologists and one 4th-year radiology resident participated as observers. All images were compared by these observers in terms of the number of disks identified.

RESULTS: Significant differences (P < .05, Bonferroni adjusted) were observed between all reconstruction and planar methods. No significant difference, however, was observed between the planar methods, and only a marginally significant difference (P < .054, Bonferroni adjusted) was observed between TACT-backprojection and TACT-minimization.

CONCLUSION: A combination of linear and nonlinear reconstruction schemes may have potential implications in terms of enhancing image visualization to provide radiologists with valuable diagnostic information.

]]> Sankararaman Suryanarayanan et al. Breast Neoplasms Female Humans Mammography Phantoms, Imaging *Radiographic Image Enhancement Sensitivity and Specificity Impact of a program of intensive surveillance and interventions targeting ventilated patients in the reduction of ventilator-associated pneumonia and its cost-effectiveness http://escholarship.umassmed.edu/infoservices/77 http://escholarship.umassmed.edu/infoservices/77 Wed, 21 May 2008 13:27:21 PDT OBJECTIVE: We hypothesized that a program of prospective intensive surveillance for ventilator-associated pneumonia (VAP) and concomitant implementations of multimodal, multidisciplinary preventive and intervention strategies would result in a reduction in the incidence of VAP and would be cost-effective.

SETTING: Medical and surgical intensive care units (ICUs) in a university teaching hospital.

INTERVENTIONS: All ventilated patients in the medical and surgical ICUs were monitored for VAP from January 1997 through December 1998. Interventions including elevation of the head of the bed, use of sterile water and replacement of stopcocks with enteral valves for nasogastric feeding tubes, and prolongation of changing of in-line suction catheters from 24 hours to as needed were implemented.

RESULTS: The rates of VAP decreased by 10.8/1,000 ventilator-days in the medical ICU (CI95, 4.65-16.91) and by 17.2/1,000 ventilator-days in the surgical ICU (CI95, 2.85-31.56) when they were compared for 1997 and 1998. With the use of the estimated cost of a VAP of dollars 4,947 from the literature, the reduction resulted in cost savings of dollars 178,092 and dollars 148,410 in the medical and surgical ICUs, respectively, for a total of dollars 326,482. In addition, dollars 25,497 was saved due to the lengthening of the time for the change of in-line suction catheters, resulting in a cost savings of dollars 351,979. This total cost savings of dollars 351,979 minus the cost of enteral valves of dollars 2,100 resulted in total net savings of dollars 349,899.

CONCLUSION: Intensive surveillance and interventions targeted at ventilated patients resulted in reduction of VAP and appeared to be cost-effective.

]]> Kwan Kew Lai et al. Cost-Benefit Analysis Cross Infection *Equipment Contamination Hospital Bed Capacity, 300 to 499 Hospitals, University Humans Infection Control Infection Control Practitioners Intensive Care Units Massachusetts Pneumonia *Sentinel Surveillance Ventilators, Mechanical Recombinant human thrombomodulin inhibits arterial neointimal hyperplasia after balloon injury http://escholarship.umassmed.edu/infoservices/76 http://escholarship.umassmed.edu/infoservices/76 Wed, 21 May 2008 13:27:17 PDT OBJECTIVE: Smooth muscle cell proliferation is a major pathophysiologic factor in injury-induced neointimal hyperplasia and recurrent stenosis. We have demonstrated that recombinant human thrombomodulin (rTM) inhibits thrombin-induced arterial smooth muscle cell proliferation in vitro. The purpose of this study was to investigate the effect of rTM on neointimal hyperplasia in vivo.

METHODS: A rabbit femoral artery balloon injury model was used. Bilateral superficial femoral arteries were deendothelialized with a 2F arterial embolectomy catheter. rTM (145 microg/kg; 2.0 microg/mL in circulation) or Tris-hydrochloride vehicle control was administered intravenously during the procedure, then either discontinued (group A) or administered twice daily for an additional 48 hours (group B). Rabbits were euthanized at 4 days and at 1, 2, and 4 weeks, and femoral artery specimens were prepared with in situ perfusion fixation and paraffin embedding. Luminal, intima, media, and whole artery areas were quantitated with digital imaging computerized planimetry. Intima-media and lumen-whole artery ratios were calculated. The injury-induced inflammatory reaction was also evaluated with light microscopy, scanning and transmission electron microscopy, and immunohistochemical and immunohistofluorescence staining.

RESULTS: In the buffer control group, neointimal hyperplasia after femoral artery balloon injury was evident at 2 weeks, and was pronounced at 4 weeks (PCONCLUSIONS: Systemic intravenous administration of rTM significantly decreases neointimal hyperplasia and improves patency in the rabbit femoral artery after balloon injury. In addition to exhibiting antithrombotic and antiproliferative effects, rTM may also invoke an anti-inflammatory mechanism, and may alter vascular remodeling in a multidimensional role to inhibit recurrent stenosis after arterial injury.

]]> Jian-ming Li et al. Angioplasty, Balloon Animals Femoral Artery Humans Hyperplasia Male Microscopy, Electron Microscopy, Electron, Scanning Rabbits Recombinant Proteins Thrombomodulin Thrombosis Time Factors Tunica Intima Vascular Patency