tbuckley/cabot-search huggingface dataset:
The Psychiatrist and the Violence Commission
Authors: W. WALTER MENNINGER
Journal: American Journal of Psychiatry (1971)

The author describes some aspects of his experience as a member of the National Commission on the Causes and Prevention of Violence, particularly how he and psychiatry in general were regarded by his fellow commissioners, the kinds of anxieties prompted by his presence on the commission, and the roles he, as a psychiatrist, was called upon to play.
Short-Term Use of Serotonin Reuptake Inhibitors and Risk of Upper Gastrointestinal Bleeding
Authors: Yen-Po Wang, Yung-Tai Chen, Chia-Fen Tsai, Szu-Yuan Li, Jiing-Chyuan Luo, Shuu- Jiun Wang, Chao-Hsiun Tang, Chia-Jen Liu, Han-Chieh Lin, Fa-Yauh Lee, Full-Young Chang, Ching-Liang Lu
Journal: American Journal of Psychiatry (2013)

The association between selective serotonin receptor inhibitors (SSRIs) and risk of upper gastrointestinal bleeding remains controversial. Previous studies have generally evaluated the issue for approximately 3 months, even though the SSRI-mediated inhibition of platelet serotonin concentrations occurs within 7-14 days. The authors explored the risk of upper gastrointestinal bleeding after short-term SSRI exposure by a case-crossover design.The records of psychiatric inpatients with upper gastrointestinal bleeding were retrieved from the Taiwan National Health Insurance Database (1998-2009). Rates of antidepressant use were compared for case and control periods with time windows of 7, 14, and 28 days. The adjusted self-matched odds ratios from a conditional logistic regression model were used to determine the association between SSRI use and upper gastrointestinal bleeding.A total of 5,377 patients with upper gastrointestinal bleeding were enrolled. The adjusted odds ratio for the risk of upper gastrointestinal bleeding after SSRI exposure was 1.67 (95% CI=1.23-2.26) for the 7-day window, 1.84 (95% CI=1.42-2.40) for the 14-day window, and 1.67 (95% CI=1.34-2.08) for the 28-day window. SSRIs with high and intermediate, but not low, affinity for serotonin transporter were associated with upper gastrointestinal bleeding. An elevated risk of upper gastrointestinal bleeding after SSRI exposure was seen in male but not female patients.Short-term SSRI use (7-28 days) is significantly associated with upper gastrointestinal bleeding. Gender differences may exist in the relationship between SSRI use and upper gastrointestinal bleeding. Physicians should carefully monitor signs of upper gastrointestinal bleeding even after short-term exposure to SSRIs, as is done with nonsteroidal anti-inflammatory drugs and aspirin.
<i>In vivo</i>probe-based confocal laser endomicroscopy in amiodarone-related pneumonia
Authors: Mathieu Salaün, Francis Roussel, Geneviève Bourg-Heckly, Christine Vever-Bizet, Stéphane Dominique, Anne Genevois, Vincent Jounieaux, Gérard Zalcman, Emmanuel Bergot, Jean-Michel Vergnon, Luc Thiberville
Journal: European Respiratory Journal (2012)

Probe-based confocal laser endomicroscopy (pCLE) allows microscopic imaging of the alveoli during bronchoscopy. The objective of the study was to assess the diagnostic accuracy of pCLE for amiodarone-related pneumonia (AMR-IP). Alveolar pCLE was performed in 36 nonsmoking patients, including 33 consecutive patients with acute or subacute interstitial lung disease (ILD), of which 17 were undergoing treatment with amiodarone, and three were amiodarone-treated patients without ILD. Nine out of 17 patients were diagnosed with high-probability AMR-IP (HP-AMR-IP) by four experts, and three separate observers. Bronchoalveolar lavage findings did not differ between HP-AMR-IP and low-probability AMR-IP (LP-AMR-IP) patients. In HP-AMR-IP patients, pCLE showed large (&gt;20 μm) and strongly fluorescent cells in 32 out of 38 alveolar areas. In contrast, these cells were observed in only two out of 39 areas from LP-AMR-IP patients, in one out of 59 areas from ILD patients not receiving amiodarone and in none of the 10 areas from amiodarone-treated patients without ILD (p&lt;0.001; HP-AMR-IP <i>versus</i> other groups). The presence of at least one alveolar area with large and fluorescent cells had a sensitivity, specificity, negative predictive value and positive predictive value for the diagnosis of AMR-IP of 100%, 88%, 100% and 90%, respectively. In conclusion, pCLE appears to be a valuable tool for the <i>in vivo</i> diagnosis of AMR-IP in subacute ILD patients.
MicroRNA-200c modulates epithelial-to-mesenchymal transition (EMT) in human colorectal cancer metastasis
Authors: Keun Hur, Yuji Toiyama, Masanobu Takahashi, Francesc Balaguer, Takeshi Nagasaka, Junichi Koike, Hiromichi Hemmi, Minoru Koi, C Richard Boland, Ajay Goel
Journal: Gut (2012)

<h3>Objective</h3> Distant metastasis is the major cause of cancer-related death in patients with colorectal cancer (CRC). Although the microRNA-200 (miR-200) family is a crucial inhibitor of epithelial-to-mesenchymal transition (EMT) in human cancer, the role of miR-200 members in the pathogenesis of metastatic CRC has not been investigated. <h3>Design</h3> Fifty-four pairs of primary CRC and corresponding matched liver metastasis tissue specimens were analysed for expression and methylation status of the miR-200 family members. Functional analysis of miR-200c overexpression was investigated in CRC cell lines, and cells were analysed for proliferation, invasion and migration. Expression of several miR-200c target genes (<i>ZEB1, ETS1</i> and <i>FLT1</i>) and EMT markers (E-cadherin and vimentin) in CRC cell lines and tissue specimens was validated. <h3>Results</h3> Liver metastasis tissues showed higher expression of miR-200c (primary CRC=1.31 vs. liver metastasis=1.59; p=0.0014) and miR-141 (primary CRC=0.14 vs. liver metastasis=0.17; p=0.0234) than did primary CRCs, which was significantly associated with hypomethylation of the promoter region of these miRNAs (primary CRC=61.2% vs. liver metastasis=46.7%; p&lt;0.0001). The invasive front in primary CRC tissues revealed low miR-200c expression by in situ hybridization analysis. Transfection of miR-200c precursors resulted in enhanced cell proliferation but reduced invasion and migration behaviours in CRC cell lines. Overexpression of miR-200c in CRC cell lines caused reduced expression of putative gene targets, and resulted in increased E-cadherin and reduced vimentin expression. The associations between miR-200c, target genes and EMT markers were validated in primary CRCs and matching liver metastasis tissues. <h3>Conclusions</h3> miR-200c plays an important role in mediating EMT and metastatic behaviour in the colon. Its expression is epigenetically regulated, and miR-200c may serve as a potential diagnostic marker and therapeutic target for patients with CRC.
Non-eosinophilic asthma: importance and possible mechanisms
Authors: J Douwes
Journal: Thorax (2002)

There is increasing evidence that inflammatory mechanisms other than eosinophilic inflammation may be involved in producing the final common pathway of enhanced bronchial reactivity and reversible airflow obstruction that characterises asthma. A review of the literature has shown that, at most, only 50% of asthma cases are attributable to eosinophilic airway inflammation. It is hypothesised that a major proportion of asthma is based on neutrophilic airway inflammation, possibly triggered by environmental exposure to bacterial endotoxin, particulate air pollution, and ozone, as well as viral infections. If there are indeed two (or more) subtypes of asthma, and if non-eosinophilic (neutrophil mediated) asthma is relatively common, this would have major consequences for the treatment and prevention of asthma since most treatment and prevention strategies are now almost entirely focused on allergic/eosinophilic asthma and allergen avoidance measures, respectively. It is therefore important to study the aetiology of asthma further, including the underlying inflammatory profiles.
Artists' intentions and artwork meanings: Some complications
Authors: Stephen Davies
Journal: Behavioral and Brain Sciences (2013)

Abstract Artists' intentions are among the primary data retrieved by art appreciators. However, artistic creation is not always deliberate; artists sometimes fail in their intentions; artists' achievements depend on artworld roles, not only intentions; factors external to the artist contribute to artwork meaning; artworks stand apart from their creators; and interpretation need not be exclusively concerned with recovering intended meaning.
Molecular distance and divergence time in carnivores and primates.
Authors: R K Wayne, B Van Valkenburgh, S J O'Brien
Journal: Molecular Biology and Evolution (1991)

Numerous studies have used indices of genetic distance between species to reconstruct evolutionary relationships and to estimate divergence time. However, the empirical relationship between molecular-based indices of genetic divergence and divergence time based on the fossil record is poorly known. To date, the results of empirical studies conflict and are difficult to compare because they differ widely in their choice of taxa, genetic techniques, or methods for calibrating rates of molecular evolution. We use a single methodology to analyze the relationship of molecular distance and divergence time in 86 taxa (72 carnivores and 14 primates). These taxa have divergence times of 0.01-55 Myr and provide a graded series of phylogenetic divergences such that the shape of the curve relating genetic distance and divergence time is often well defined. The techniques used to obtain genetic distance estimates include one- and two-dimensional protein electrophoresis, DNA hybridization, and microcomplement fixation. Our results suggest that estimates of molecular distance and divergence time are highly correlated. However, rates of molecular evolution are not constant; rather, in general they decline with increasing divergence time in a linear fashion. The rate of decline may differ according to technique and taxa. Moreover, in some cases the variability in evolutionary rates changes with increasing divergence time such that the accuracy of nodes in a phylogenetic tree varies predictably with time.
Immune Reconstitution Inflammatory Syndrome Associated With Kaposi's Sarcoma
Authors: M. Bower, M. Nelson, A.M. Young, C. Thirlwell, T. Newsom-Davis, S. Mandalia, T. Dhillon, P. Holmes, B.G. Gazzard, J. Stebbing
Journal: Journal of Clinical Oncology (2005)

A proportion of patients with HIV infection who subsequently receive highly active antiretroviral therapy (HAART) exhibit a deterioration in their clinical status, despite control of virologic and immunologic parameters. This clinical response, known as the immune reconstitution inflammatory syndrome (IRIS), occurs secondary to an immune response against previously diagnosed pathogens.From our cohort of 5,832 patients treated in the HAART era, we identified 150 therapy-naive patients with a first presentation of Kaposi's sarcoma (KS). Their clinicopathologic features and progress were recorded prospectively.After commencing HAART, ten patients (6.6%) developed progressive KS, which we identify as IRIS-associated KS. In a comparison of these individuals with those whose KS did not progress, we found that IRIS-KS occurred in patients with higher CD4 counts (P = .03), KS-associated edema (P = .01), and therapy with both protease inhibitors and non-nucleosides together (P = .03). Time to treatment failure was similar for both groups, although the CD4 count declined more rapidly at first, in those patients with IRIS-associated KS. Despite this initial decline, in our clinical experience HAART could be successfully continued in those with IRIS-associated KS.We have identified IRIS-KS in a cohort of HIV patients with KS who start HAART.
Small-Molecule Anticancer Compounds Selectively Target the Hemopexin Domain of Matrix Metalloproteinase-9
Authors: Antoine Dufour, Nicole S. Sampson, Jian Li, Cem Kuscu, Robert C. Rizzo, Jennifer L. DeLeon, Jizu Zhi, Nadia Jaber, Eric Liu, Stanley Zucker, Jian Cao
Journal: Cancer Research (2011)

Lack of target specificity by existing matrix metalloproteinase (MMP) inhibitors has hindered antimetastatic cancer drug discovery. Inhibitors that bind to noncatalytic sites of MMPs and disrupt protease signaling function have the potential to be more specific and selective. In this work, compounds that target the hemopexin (PEX) domain of MMP-9 were identified using an in silico docking approach and evaluated using biochemical and biological approaches. Two of the selected compounds interfere with MMP-9-mediated cancer cell migration and proliferation in cells expressing exogenous or endogenous MMP-9. Furthermore, these inhibitors do not modulate MMP-9 catalytic activity. The lead compound, N-[4-(difluoromethoxy)phenyl]-2-[(4-oxo-6-propyl-1H-pyrimidin-2-yl)sulfanyl]-acetamide, specifically binds to the PEX domain of MMP-9, but not other MMPs. This interaction between the compound and the PEX domain results in the abrogation of MMP-9 homodimerization and leads to blockage of a downstream signaling pathway required for MMP-9-mediated cell migration. In a tumor xenograft model, this pyrimidinone retarded MDA-MB-435 tumor growth and inhibited lung metastasis. Thus, we have shown for the first time that a novel small-molecule interacts specifically with the PEX domain of MMP-9 and inhibits tumor growth and metastasis by reducing cell migration and proliferation.
The relative stress on the Achilles tendon during ambulation in an ankle immobiliser: implications for rehabilitation after Achilles tendon repair
Authors: K H Akizuki, E J Gartman, B Nisonson, S Ben-Avi, M P McHugh
Journal: British Journal of Sports Medicine (2001)

After Achilles tendon repair, immediate weightbearing and immobilisation closer to neutral plantarflexion are thought to limit atrophy and stiffness, but may place deleterious stress on the repair.To estimate the relative stress on the Achilles tendon during weightbearing with immobilisation in varying degrees of plantarflexion.Electromyographic (EMG) activity from the plantarflexors was recorded during walking in 10 subjects (six men, four women) without ankle pathology. Four walking conditions were examined: (a) normal walking; (b) immobilised (cam-walker) in neutral plantarflexion; (c) immobilised with a 0.5 inch heel lift; (d) immobilised with a 1 inch heel lift. EMG activity relative to plantarflexor torque was determined for each subject during isometric contractions at 25%, 50%, 75%, and 100% of maximal voluntary contraction (MVC). EMG activity during walking was calculated as a percentage of MVC based on the EMG-torque relation during graded isometric contractions.During normal walking, the plantarflexor torque was estimated to be 30 (12)% (mean (SD)) of MVC, compared with 21 (15)% MVC for immobilisation in neutral (p<0.05), 17 (15)% MVC with the addition of a 0.5 inch heel lift (p<0.01), and 12 (12)% MVC with the addition of a 1 inch heel lift (p<0.01). The 1 inch heel lift resulted in less than 10 degrees plantarflexion in all subjects.When the ankle is immobilised, stress on the Achilles tendon is determined by the degree of plantarflexion and the contractile activity of the plantarflexors. In the immobilised ankle, the addition of a 1 inch heel lift was sufficient to minimise plantarflexor activity during walking.
Efficacy of Corticosteroids in Community-acquired Pneumonia
Authors: Dominic Snijders, Johannes M. A. Daniels, Casper S. de Graaff, Tjip S. van der Werf, Wim G. Boersma
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Some studies have shown a beneficial effect of corticosteroids in patients with community-acquired pneumonia (CAP), possibly by diminishing local and systemic antiinflammatory host response.To assess the efficacy of adjunctive prednisolone treatment in patients hospitalized with CAP.Hospitalized patients, clinically and radiologically diagnosed with CAP using standard clinical and radiological criteria, were randomized to receive 40 mg prednisolone for 7 days or placebo, along with antibiotics. Primary outcome was clinical cure at Day 7. Secondary outcomes were clinical cure at Day 30, length of stay, time to clinical stability, defervescence, and C-reactive protein. Disease severity was scored using CURB-65 (a severity index for community-acquired pneumonia evaluating Confusion, blood Urea nitrogen, Respiratory rate, Blood pressure, and age 65 or older) and Pneumonia Severity Index.We enrolled 213 patients. Fifty-four (25.4%) patients had a CURB-65 score greater than 2, and 93 (43.7%) patients were in Pneumonia Severity Index class IV-V. Clinical cure at Days 7 and 30 was 84/104 (80.8%) and 69/104 (66.3%) in the prednisolone group and 93/109 (85.3%) and 84/109 (77.1%) in the placebo group (P = 0.38 and P = 0.08). Patients on prednisolone had faster defervescence and faster decline in serum C-reactive protein levels compared with placebo. Subanalysis of patients with severe pneumonia did not show differences in clinical outcome. Late failure (>72 h after admittance) was more common in the prednisolone group (20 patients, 19.2%) than in the placebo group (10 patients, 6.4%; P = 0.04). Adverse events were few and not different between the two groups.Prednisolone (at 40 mg) once daily for a week does not improve outcome in hospitalized patients with CAP. A benefit in more severely ill patients cannot be excluded. Because of its association with increased late failure and lack of efficacy prednisolone should not be recommended as routine adjunctive treatment in CAP.
The Sensitivity and Specificity of Nonmydriatic Digital Stereoscopic Retinal Imaging in Detecting Diabetic Retinopathy
Authors: Jehanara Ahmed, Thomas P. Ward, Sven-Eric Bursell, Lloyd M. Aiello, Jerry D. Cavallerano, Robert A. Vigersky
Journal: Diabetes Care (2006)

OBJECTIVE—The objective of this study was to determine the sensitivity and specificity of Joslin Vision Network nonmydriatic digital stereoscopic retinal imaging (NMDSRI) as a screening tool in detecting diabetic retinopathy. RESEARCH DESIGN AND METHODS—We reviewed the records of 244 patients with diabetes who had a dilated funduscopic examination (DFE) and NMDSRI done within 1 year of each other at four locations in the metropolitan Washington, DC, area. The images were transmitted through a local area network to a central reading location where they were graded by a single retinal specialist. RESULTS—Images of 482 eyes from 243 patients were included in the study. Four images did not transmit, and 35% of the images were not gradable. Of the remaining 311 eyes, there was 86% agreement in the grading between NMDSRI and DFE: 227 eyes with no diabetic retinopathy and 40 eyes with diabetic retinopathy. In 46 eyes (15%) there was a disagreement between gradings made by the two techniques. NMDSRI detected diabetic retinopathy in 35 eyes reported as normal by DFE, and in the remaining 11 eyes, the DFE grade was one grade higher than the NMDSRI grade. Adjudicated nonconcordant examinations were within one grade. In the 76 eyes with diabetic retinopathy, retinal thickness could not be assessed in 17 (21%) eyes. When the NMDSRI result was gradable, the overall sensitivity of NMDSRI was 98% and the specificity was 100% for retinopathy within one grade of the DFE. In the limited number of eyes that had diabetic retinopathy with macular edema (six), agreement with the clinical examination was 100%. CONCLUSIONS—NMDSRI is a sensitive and specific method for the screening and diagnosis of diabetic retinopathy, which may help improve compliance with the standards of eye care for patients with diabetes.
The antigen-presenting activities of Ia+ dendritic cells shift dynamically from lung to lymph node after an airway challenge with soluble antigen.
Authors: W Xia, C E Pinto, R L Kradin
Journal: The Journal of Experimental Medicine (1995)

Dendritic cells (DC) are widely distributed in the lung where they are distinguished by their morphology and class II major histocompatibility complex (Ia) antigen expression. Although a role for DC as pulmonary antigen-presenting cell (APC) has been suggested, little is currently known concerning how these cells respond to inhaled antigens in vivo. Hen-egg lysozyme (HEL) was injected intratracheally into Lewis rats; DC were subsequently purified from the lung and regional lymph nodes (LN) at intervals of up to 14 d and examined for their ability to stimulate the proliferation of HEL-immune T cells in vitro in the absence of added HEL. Pulmonary DC displayed APC activities at 3 h and for up to 7 d after the injection of antigen. Dendritic cells in the draining hilar LN showed APC activities that appeared at 24 h, peaked at day 3, and then diminished progressively. After the primary sensitization, HEL-immune T cells were detected in hilar LN but not in the lung. A second airway challenge with HEL at day 14 yielded an antigen-specific pulmonary immune response, characterized histologically by the accumulation of mononuclear cells around lung venules. We conclude that APC activities shift from lung to lymph node during the response to inhaled antigen.
Clinical Features and Health-Care Costs of Diabetic Nephropathy
Authors: Barbara E Narins, Robert G Narins
Journal: Diabetes Care (1988)

The nephropathy complicating insulin-dependen diabetes mellitus (IDDM) has been well studied, but that complicating non-insulin-dependent diabetes mellitus (NIDDM) is less well defined. In patients with IDDM, the gl merular filtration rate is often increased early in the course of the disease, approaches normal with insulin therapy, but tends to remain slightly elevated throughout the ensuing 10–15 yr of insulin dependency. After t e onset of overt azotemia, end-stage renal disease (ESRD) develops in ∼5 yrs. Proteinuria may be intermittently positive in the earliest stages of diabetes, evolving into intermittent and then persistent mincroalbuminura, which in turn blossoms into mincroalbuminura. Because 40–50% of IDDM patients develop proteinuria and two thirds of this subpopulation develop ESRD, some 20–30% of any given cohort of IDDM patients eventually need dialysis or transplantation. Evidence indicates that diabetic nephropathy is associated with a greater incidence of eye, nerve, heart, and peripheral vascular disease. Nondiabetic renal disease complicating IDDM and NIDDM is associated with a lesser frequency and severity of these extrarenal manifestations, the prevalence of retin pathy increases with advancing nephropathy. Roughly two-thirds of the deaths from IDDM are related to renal f ilure, and most of the remainder are caused by associated cardiovascular disease. Transplantation from living relatives carries the best prognosis for survival, and little difference is seen between hemodialysis, peritoneal dialysis, and cadaver transplantation. The health-care costs of treating diabetic nephropathy are also reviewed.