tbuckley/cabot-search huggingface dataset:
Hodgkin's disease presenting as liver abscesses.
Authors: A Zaman, P N Bramley, J Wyatt, A Simmons, M S Losowsky, R Bolton
Journal: Gut (1991)

A patient is reported who presented with sterile hepatic abscesses which proved to be the first manifestation of Hodgkin9s disease. He failed to improve with antibiotic treatment but responded to combined chemotherapy. Liver involvement as the first sign of Hodgkin9s disease is rare. Liver abscesses due to Hodgkin9s disease seem to be previously unreported.
Real-time, two-dimensional echocardiographic features of pacemaker perforation.
Authors: B Gondi, N C Nanda
Journal: Circulation (1981)

Five patients (four adults and one child) with clinically suspected myocardial perforation by temporary transvenous pacemakers were studied by real-time, two-dimensional echocardiography. In three patients, the catheters were visualized passing through the right ventricular apical wall with the tip located outside the cardiac border. In one patient the catheter perforated the atrioventricular septum and entered the left ventricle with the tip lodged against the posterior wall. In another patient, the catheter had partially penetrated the ventricular septum near the apex. Pericardial effusion was observed in two patients, in one of whom it was localized to the site of perforation. No patient had evidence of cardiac tamponade. In four patients, the catheters were withdrawn under echocardiographic visualization and the catheter tips could be seen moving from the abnormal locations back into the right-heart chambers. Perforation was verified at autopsy in two patients, including one in whom the catheter was not withdrawn. Real-time, two-dimensional echocardiography appears to be valuable in the diagnosis of pacemaker perforation.
Use of Computed Tomography in Diagnosing Ventral Hernia Recurrence
Authors: Julie L. Holihan, Burzeen Karanjawala, Annie Ko, Erik P. Askenasy, Eduardo J. Matta, Latifa Gharbaoui, Joseph P. Hasapes, Varaha S. Tammisetti, Chakradhar R. Thupili, Zeinab M. Alawadi, Ioana Bondre, Juan R. Flores-Gonzalez, Lillian S. Kao, Mike K. Liang
Journal: JAMA Surgery (2015)

<h3>Importance</h3> Physical examination misses up to one-third of ventral hernia recurrences seen on radiologic imaging. However, tests such as computed tomographic (CT) imaging are subject to interpretation and require validation of interobserver reliability. <h3>Objective</h3> To determine the interobserver reliability of CT scans for detecting a ventral hernia recurrence among surgeons and radiologists. We hypothesized there would be significant disagreement in the diagnosis of a ventral hernia recurrence among different observers. Our secondary aim was to determine reasons for disagreement in the interpretation of CT scans. <h3>Design, Setting, and Participants</h3> One hundred patients who underwent ventral hernia repair from 2010-2011 at an academic health care center with a postoperative CT scan were randomly selected from a larger cohort. This study was conducted from July 2014 to March 2015. Prospective assessment of the presence or absence of a recurrent ventral hernia on CT scans was compared among 9 blinded reviewers and the radiology report. Five reviewers (consensus group) met to discuss all CT scans with disagreement. The discussion was assessed for keywords and key concepts. The remaining 4 reviewers (validation group) read the consensus group recommendations and reassessed the CT scans. Pre- and post-review κ were calculated; the post-review assessments were compared with clinical examination findings. <h3>Main Outcomes and Measures</h3> Interobserver reliability in determining hernia recurrence radiographically. <h3>Results</h3> Of 100 CT scans, there was disagreement among all 9 reviewers and the radiology report on the presence/absence of a ventral hernia in 73 cases (κ = 0.44; 95% CI, 0.35-0.54;<i>P</i> &lt; .001). Following discussion among the consensus group, there remained disagreement in 10 cases (κ = 0.91; 95% CI, 0.83-0.95;<i>P</i> &lt; .001). Among the validation group, the κ value had a slight improvement from 0.21 (95% CI, 0.12-0.33) to 0.34 (95% CI, 0.23-0.46) (<i>P</i> &lt; .001) after reviewing the consensus group proposals. There was disagreement between clinical examination and the consensus group assessment of CT scans on the presence/absence of a ventral hernia in 25 cases. The concepts most frequently discussed were the absence of an accepted definition for a radiographic ventral hernia and differentiating pseudorecurrence from recurrence. <h3>Conclusions and Relevance</h3> Owing to the high interobserver variability, CT scan was not associated with reliable diagnosing in ventral hernia recurrence. Consensus guidelines and improved communication between surgeon and radiologist may decrease interobserver variability.
Comparisons of health status scores with MRC grades in COPD: implications for the GOLD 2011 classification
Authors: Paul W. Jones, Lukasz Adamek, Gilbert Nadeau, Norbert Banik
Journal: European Respiratory Journal (2012)

The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy document recommends assessment of chronic obstructive pulmonary disease (COPD) using symptoms and future exacerbation risk, employing two score cut-points: COPD Assessment Test (CAT) score ≥ 10 or modified Medical Research Council dyspnoea scale (mMRC) grade ≥ 2. To explore the equivalence of these two symptom cut-points, the relationship between the CAT and the mMRC and St George's Respiratory Questionnaire (SGRQ), the Short-form Health Survey and the Functional Assessment of Chronic Illness Therapy Fatigue scores were retrospectively analysed using a primary care dataset. Data from 1817 patients (mean ± SD forced expiratory volume in 1 s 1.6 ± 0.6 L) showed a significant association between mMRC grades and all health status scores (ANOVA p<0.0001). mMRC grade 1 was associated with significant levels of health status impairment (SGRQ 39.4 ± 15.5 and CAT 15.7 ± 7.0); even patients with mMRC grade 0 had modestly elevated scores (SGRQ 28.5 ± 15.1 and CAT 11.7 ± 6.8). An mMRC grading ≥ 2 categorised 57.2% patients with low symptom (groups A and C) versus 17.2% with the CAT. Using the mMRC cut-point (≥ 1) resulted in similar GOLD group categorisations as the CAT (18.9%). The mMRC showed a clear relationship with health status scores; even low mMRC grades were associated with health status impairment. Cut-points of mMRC grade ≥ 1 and CAT score ≥ 10 were approximately equivalent in determining low-symptom patients. The GOLD assessment framework may require refinement.
Proliferative activity of cyst epithelium in human renal cystic diseases.
Authors: T Nadasdy, Z Laszik, G Lajoie, K E Blick, D E Wheeler, F G Silva
Journal: Journal of the American Society of Nephrology (1995)

Increased proliferative activity of the renal tubular epithelium is thought to be a prerequisite for renal cyst formation by many investigators. However, in humans, the exact in vivo proliferation rate of epithelial cells lining these cysts is not known. In this study, which used immunohistochemical methods with an antibody to proliferating cell nuclear antigen (PCNA), the proliferation index (PI) (percentage of PCNA positive cell nuclei among epithelial cells lining the renal cysts) was determined in 10 cases of autosomal dominant polycystic kidney disease (ADPKD), 8 cases of autosomal recessive polycystic kidney disease (ARPKD), and 8 cases of acquired cystic kidney disease (ACKD). Cysts with proximal and distal nephron phenotype and cysts with markedly thickened basement membranes, as well as cysts lined by atrophic (flattened), "regular" (cuboidal or cylindrical), and hyperplastic epithelium, were evaluated separately. The overall PI of cyst epithelium (excluding hyperplastic cysts) was 2.58 in ADPKD, was 10.5 in ARPKD, and was 3.61 in ACKD. Overall, there were only minor differences in the PI between the various types of cysts. Cysts with hyperplastic epithelium in ACKD (unlike in ADPKD) showed a high PI (9.1). For comparison, the PI of two renal cell carcinomas occurring in two ACKD cases was also determined (13.70 and 8.67%). The PI of tubular epithelium in normal kidneys was only 0.22 to 0.33%, depending on the tubule segment. In contrast, in polycystic kidneys, those noncystic segments of the nephron from which the cysts are thought to originate (distal nephron (specifically collecting duct)) in ARPKD, primarily distal in ADPKD, proximal and distal in ACKD, had PI values similar to those of the cyst epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)
Loss of Estrogen Receptor Signaling Triggers Epigenetic Silencing of Downstream Targets in Breast Cancer
Authors: Yu-Wei Leu, Pearlly S. Yan, Meiyun Fan, Victor X. Jin, Joseph C. Liu, Edward M. Curran, Wade V. Welshons, Susan H. Wei, Ramana V. Davuluri, Christoph Plass, Kenneth P. Nephew, Tim H-M. Huang
Journal: Cancer Research (2004)

Abstract Alterations in histones, chromatin-related proteins, and DNA methylation contribute to transcriptional silencing in cancer, but the sequence of these molecular events is not well understood. Here we demonstrate that on disruption of estrogen receptor (ER) α signaling by small interfering RNA, polycomb repressors and histone deacetylases are recruited to initiate stable repression of the progesterone receptor (PR) gene, a known ERα target, in breast cancer cells. The event is accompanied by acquired DNA methylation of the PR promoter, leaving a stable mark that can be inherited by cancer cell progeny. Reestablishing ERα signaling alone was not sufficient to reactivate the PR gene; reactivation of the PR gene also requires DNA demethylation. Methylation microarray analysis further showed that progressive DNA methylation occurs in multiple ERα targets in breast cancer genomes. The results imply, for the first time, the significance of epigenetic regulation on ERα target genes, providing new direction for research in this classical signaling pathway.
Surfactant changes during experimental pneumocystosis are related to Pneumocystis development
Authors: EM Aliouat, R Escamilla, C Cariven, C Vieu, C Mullet, E Dei-Cas, MC Prevost
Journal: European Respiratory Journal (1998)

Pneumocystosis-related surfactant changes have been reported in both humans and corticosteroid-treated experimental hosts. As corticosteroids induce an increase in pulmonary surfactant, some findings could be considered as controversial. The aim of this study was to investigate whether the surfactant composition changes during experimental pneumocystosis were related to the Pneumocystis development. In this work two corticosteroid-untreated animal models were used: rabbits, which develop spontaneous pneumocystosis at weaning; and severe combined immunodeficiency mice, which were intranasally inoculated with Pneumocystis carinii. Surfactant phospholipid and protein content was explored by bronchoalveolar lavage. The in vitro effect of surfactant on P. carinii growth was also explored. In the two models, the surfactant phospholipid/protein ratio was significantly increased, whereas parasite rates were low. This ratio decreases with the slope increase of the parasite growth curve. These early surfactant changes suggested that Pneumocystis proliferation requires alveolar lining fluid changes, and that normal surfactant is not suitable for parasite development. In this way, in vitro experiments presented here have revealed an inhibitory effect of synthetic or seminatural surfactants on the P. carinii growth. Further studies are needed to determine how Pneumocystis induces the reported early modifications of the surfactant, and why the parasite development is inhibited by pulmonary surfactant.
Acute anaphylaxis following midline catheterisation in a patient with cystic fibrosis
Authors: C S Haworth, R M. Niven, A J Moorcroft, A Phillips, M E Dodd, A K Webb
Journal: Thorax (1999)

A 16 year old male with cystic fibrosis experienced an acute life threatening anaphylactic reaction following the insertion of an Ohmeda Hydrocath(TM) midline peripheral venous catheter. The catheter was immediately withdrawn and treatment with intravenous adrenaline, hydrocortisone, chlorpheniramine, and colloid over a 24 hour period resulted in a gradual resolution of symptoms.
Visceral and Central Abdominal Fat and Anthropometry in Relation to Diabetes in Asian Indians
Authors: Mohan Anjana, Sreedharan Sandeep, Raj Deepa, Karani Santhanakrishnan Vimaleswaran, Syed Farooq, Viswanathan Mohan
Journal: Diabetes Care (2004)

The objective of the study was to examine body fat distribution using computed tomography (CT), dual-energy X-ray absorptiometry (DEXA), and anthropometry in relation to type 2 diabetes in urban Asian Indians.This is a case-control study of 82 type 2 diabetic and 82 age- and sex-matched nondiabetic subjects from the Chennai Urban Rural Epidemiology Study, an ongoing epidemiological study in southern India. Visceral, subcutaneous, and total abdominal fat were measured using CT, while DEXA was used to measure central abdominal and total body fat. Anthropometric measures included BMI, waist circumference, sagittal abdominal diameter (SAD), and waist-to-hip ratio.Visceral and central abdominal fat showed a strong correlation with each other (P <0.0001), and kappa analysis revealed a fairly good agreement between tertiles of visceral and central abdominal fat (kappa=0.44, P <0.0001). Diabetic subjects had significantly higher visceral (P=0.005) and central abdominal (P=0.011) fat compared with nondiabetic subjects. Waist circumference and SAD showed a strong correlation with visceral (P <0.01) and central abdominal (P <0.0001) fat in both diabetic and nondiabetic subjects. Logistic regression analysis revealed visceral (odds ratio [OR] 1.011, P=0.004) and central abdominal (OR 1.001, P=0.013) fat to be associated with diabetes, even after adjusting for age and sex.Visceral and central abdominal fat showed a strong association with type 2 diabetes. Both measures correlated well with each other and with waist circumference and SAD in diabetic and nondiabetic urban Asian Indians.
Impact of gastroenterologist care on health outcomes of hospitalised ulcerative colitis patients
Authors: Sanjay K Murthy, A Hillary Steinhart, Jill Tinmouth, Peter C Austin, Geoffrey C Nguyen
Journal: Gut (2012)

<h3>Objectives</h3> To evaluate the impact of in-hospital gastroenterologist care, relative to other provider care, on health outcomes of hospitalised Ulcerative colitis (UC) patients. <h3>Design</h3> A population-based cohort study of 4278 UC patients hospitalised between 2002 and 2008 was conducted in Ontario, Canada. The primary outcome was in-hospital mortality risk. <h3>Results</h3> UC patients admitted under non-gastroenterologists had a higher in-hospital mortality rate (1.1 vs 0.2%, p&lt;0.0001) but a similar in-hospital colectomy rate (5.4 vs 4.9%, p=0.69) as compared to UC patients admitted under gastroenterologists. Following covariate adjustment, non-gastroenterologist care was associated with a greater in-hospital mortality risk relative to gastroenterologist care (adjusted OR (aOR) 3.28, 95% CI 1.03 to 10.5). This increased mortality risk was observed in patients admitted to other internists (OR 5.49, 95% CI 1.75 to 17.2) and general practitioners (OR 6.02, 95% CI 1.84 to 19.7), with a trend towards greater mortality risk among patients admitted to general surgeons (OR 3.49, 95% CI 0.90 to 13.6). Among patients who were discharged from hospital colectomy-free, those who were admitted under non-gastroenterologists had a greater one-year risk of death than patients who were admitted under gastroenterologists (adjusted HR 2.07, 95% CI 1.26 to 3.40). The type of hospital provider did not impact in-hospital or one-year colectomy risks or the risk of hospital re-admission in this cohort. <h3>Conclusions</h3> Primary in-hospital gastroenterologist care was associated with decreased in-hospital and one-year mortality risks among hospitalised UC patients. Optimised care strategies by experienced specialists may confer important health advantages in this patient population.
Lebrikizumab may benefit a subset of patients with asthma
Authors: Sasiharan Sithamparanathan
Journal: Thorax (2011)

Interleukin 13 (IL-13), a cytokine of type 2 helper T cells, may contribute to the heterogeneity of asthma in terms of clinical course and response to treatment. IL-13 leads to the production of periostin, a protein that may cause airway remodelling.

In this randomised, double-blind, placebo-controlled study, lebrikizumab, a monoclonal antibody that binds to IL-13 thereby inhibiting …
The Use of Biomarkers in Human Pharmacology (Phase I) Studies
Authors: A.F. Cohen, J. Burggraaf, J.M.A. van Gerven, M. Moerland, G.J. Groeneveld
Journal: The Annual Review of Pharmacology and Toxicology (2014)

The development of a new medicine is a risky and costly undertaking that requires careful planning. This planning is largely applied to the operational aspects of the development and less so to the scientific objectives and methodology. The drugs that will be developed in the future will increasingly affect pathophysiological pathways that have been largely unexplored. Such drug prototypes cannot be immediately introduced in large clinical trials. The effects of the drug on normal physiology, pathophysiology, and eventually the desired clinical effects will need to be evaluated in a structured approach, based on the definition of drug development as providing answers to important questions by appropriate clinical studies. This review describes the selection process for biomarkers that are fit-for-purpose for the stage of drug development in which they are used. This structured and practical approach is widely applicable and particularly useful for the early stages of innovative drug development.
Selective Inhibition of ErbB2-Overexpressing Breast Cancer <i>In vivo</i> by a Novel TAT-Based ErbB2-Targeting Signal Transducers and Activators of Transcription 3–Blocking Peptide
Authors: Ming Tan, Keng-Hsueh Lan, Jun Yao, Chien-Hsing Lu, Menghong Sun, Christopher L. Neal, Jing Lu, Dihua Yu
Journal: Cancer Research (2006)

Abstract ErbB2 is an excellent target for cancer therapies. Unfortunately, the outcome of current therapies for ErbB2-positive breast cancers remains unsatisfying due to resistance and side effects. New therapies for ErbB2-overexpressing breast cancers continue to be in great need. Peptide therapy using cell-penetrating peptides (CPP) as peptide carriers is promising because the internalization is highly efficient, and the cargoes delivered can be bioactive. However, the major obstacle in using these powerful CPPs for therapy is their lack of specificity. Here, we sought to develop a peptide carrier that could introduce therapeutics specifically to ErbB2-overexpressing breast cancer cells. By modifying the HIV TAT-derived CPP and conjugating anti-HER-2/neu peptide mimetic (AHNP), we developed the peptide carrier (P3-AHNP) that specifically targeted ErbB2-overexpressing breast cancer cells in vitro and in vivo. A signal transducers and activators of transcription 3 (STAT3)–inhibiting peptide conjugated to this peptide carrier (P3-AHNP-STAT3BP) was delivered more efficiently into ErbB2-overexpressing than ErbB2 low-expressing cancer cells in vitro and successfully decreased STAT3 binding to STAT3-interacting DNA sequence. P3-AHNP-STAT3BP inhibited cell growth in vitro, with ErbB2-overexpressing 435.eB breast cancer cells being more sensitive to the treatment than the ErbB2 low-expressing MDA-MB-435 cells. Compared with ErbB2 low-expressing MDA-MB-435 xenografts, i.p. injected P3-AHNP-STAT3BP preferentially accumulated in 435.eB xenografts, which led to more reduction of proliferation and increased apoptosis and targeted inhibition of tumor growth. This novel peptide delivery system provided a sound basis for the future development of safe and effective new-generation therapeutics to cancer-specific molecular targets. (Cancer Res 2006; 66(7): 3764-72)
Heterogeneity and biased T cell receptor alpha/beta repertoire of mucosal CD8+ cells from murine large intestine: implications for functional state.
Authors: A R Ibraghimov, R G Lynch
Journal: The Journal of Experimental Medicine (1994)

Up to 90% of CD8+ intraepithelial lymphocytes (IEL) of the murine large intestine (LI) belong to the alpha/beta T cell lineage and consist of two subsets. One subset expresses both alpha and beta subunits of the CD8 coreceptor, and is uniformly Thy1+, CD5+, B220-, CD2+, CD28+. The CD8 alpha+beta+ LI-IEL exclude self-reacting V beta structures, and readily proliferate in vivo in response to T cell receptor-mediated stimuli. The CD8 alpha+beta- subset of TCR-alpha/beta+ LI-IEL is Thy1-/+, CD5-, B220+, CD2+/-, and CD28-. It contains cells with potentially self-reacting V beta s and is responsive in vivo to high doses of anti-TCR-alpha/beta monoclonal antibody (mAb), but not to bacterial superantigens. Both subsets are abundant in LI-IEL of old nude mice, and CD8 alpha+beta+ LI-IEL in nude mice undergo the same V beta deletions as in euthymic mice of the same background. Both subsets express the intestinal T cell-specific integrin alpha M290 beta 7, known to be a homing receptor for IEL. Unusually high proportions of CD69+ cells within both subsets indicate chronic activation. The proportions of CD69+ and alpha M290 beta 7+ cells within the CD8 alpha+beta+ subset increase with age, probably due to constant antigenic challenge. We propose that CD8 alpha+beta+ and CD8 alpha+beta- subsets of LI-IEL permanently reside in LI and represent a lineage different from spleen and lymph node CD8+ T cells. The CD8 alpha+beta+ undergoes negative selection, and is responsive to TCR-mediated stimuli. The CD8 alpha+beta- subset of LI-IEL is a subject of distinct selection mechanisms, and has low responsiveness to TCR-mediated stimuli.
Atypical white matter volume development in children following craniospinal irradiation
Authors: Wilburn E. Reddick, John O. Glass, Shawna L. Palmer, Shingjie Wu, Amar Gajjar, James W. Langston, Larry E. Kun, Xiaoping Xiong, Raymond K. Mulhern
Journal: Neuro-Oncology (2005)

Most children with medulloblastoma (MB), the second most common pediatric brain tumor, have a 70% probability of survival. However, survivors who receive aggressive therapy are at significant risk of cognitive deficits that have been associated with lower volumes of normal-appearing white matter (NAWM). We hypothesized that cranial irradiation inhibited normal brain volume development in these survivors. We retrospectively analyzed 324 MRI studies of 52 patients with histologically proven MB treated with surgery and 35 to 40 Gy craniospinal irradiation, with or without chemotherapy. The volume of NAWM and that of cerebrospinal fluid were quantified from a single index section and compared with those of healthy, age-similar control subjects. A quadratic random coefficient model was used to identify trends in brain volume with increasing age. Patients treated for MB at younger ages demonstrated substantially less development of NAWM volume than did their healthy peers. Younger age at the time of irradiation and the need for a ventricular shunt were significantly associated with reduced NAWM volume. NAWM and craniospinal fluid volume differences between patients who had shunts and those without resolved over a period of four to five years. NAWM volume is known to be associated with neurocognitive test performance, which shows deficiencies after cranial irradiation early in life. Therefore, volumetric monitoring of brain development can be used to guide the care of survivors, assess the toxicity of previous and current clinical trials, and aid in the design of therapies that minimize toxicity.