tbuckley/cabot-search huggingface dataset:
P109 Do specialist non-CF bronchiectasis clinics improve quality of care?
Authors: LJ Finney, V Beasley, T Wan, H Cahill, M Berry
Journal: Thorax (2013)

<h3>Introduction</h3> Non Cystic Fibrosis (CF) Bronchiectasis is increasingly recognised as a major cause of respiratory morbidity in the UK. Previous BTS audits have shown poor adherence to the 2010 BTS guidelines for non-CF bronchiectasis. Specialist clinics for cystic fibrosis have been shown to improve survival and quality of life in CF bronchiectasis. The majority of patients with non-CF bronchiectasis are managed in general respiratory clinics. We hypothesised that the introduction of a specialist clinic for non-CF bronchiectasis would improve compliance with the BTS 2012 standards of care for non-CF bronchiectasis. <h3>Methods</h3> Data was collected prospectively as part of the BTS national bronchiectasis audit 2012. All patients with bronchiectasis attending an outpatient respiratory clinic in Imperial NHS Trust between 1/10/12 to 31/11/12 were eligible for inclusion. Comparison between groups was performed using fischers exact test using GraphPad Prism software. <h3>Results</h3> Forty patients attended a specialist bronchiectasis clinic, 56 patients were reviewed in a general respiratory clinic. Patients under the care of a bronchiectasis specialist were significantly more likely to have an individualised management plan (97.4% vs. 66.0% p = 0.002), to have their sputum sent for culture when clinically stable (82.5% vs. 55.4% p = 0.0018), and be investigated for cystic fibrosis (17.9% vs. 4.9% p = 0.007). They were significantly more likely to have grown a pseudomonas, staph aureus or a gram negative bacteria in their sputum in the last 12 months (29.4% vs. 5.4%, p = 0.0036) and be treated with either oral or nebulised long term antibiotics (35.0% vs. 12.5%, p = 0.012) graph 1. <h3>Conclusions</h3> Patients attending specialist bronchiectasis clinics were more likely to be managed according to BTS quality standards. Specialist non-CF bronchiectasis clinics may improve quality of care. Further longitudinal studies are needed to investigate if specialist clinics improve clinical outcomes.
STROKE AND SYSTEMIC EMBOLISM PROPHYLAXIS IN NON-VALVULAR ATRIAL FIBRILLATION: A NETWORK META-ANALYSIS COMPARING WARFARIN, NOVEL ORAL ANTICOAGULANTS AND WATCHMAN DEVICE
Authors: Akhil Parashar, Karan Sud, Adriani Nikolakopoulou, Shikhar Agarwal, Mehak Bassi, Oussama Wazni, Amar Krishnaswamy, Walid Saliba, E. Murat Tuzcu, Samir Kapadia
Journal: Journal of the American College of Cardiology (2016)
USE OF NOVEL INTRACORONARY TECHNOLOGY TO INVESTIGATE THE EFFECT OF COLD AIR INHALATION DURING EXERCISE ON CORONARY MICROVASCULAR RESISTANCE AND BLOOD FLOW: CROSS-SECTIONAL STUDY IN 39 CORONARY ARTERY DISEASE PATIENTS
Authors: Rupert Williams, Kaleab Asrress, Matthew Lumley, Satpal Arri, Tiffany Patterson, Howard Ellis, Vasi Manou-Stathopoulou, Muhammed Khawaja, Natalia Briceno, Konstantinos Moschonas, Brian Clapp, Divaka Perera, Sven Plein, Michael Marber, Simon Redwood
Journal: Journal of the American College of Cardiology (2016)
Structured and persistently reinforced patient education can work
Authors: M. Trento, M. Porta
Journal: BMJ (2012)

Snoek argues that self management education is of limited effect because it did not persistently improve metabolic control in some recently published clinical trials in patients with type 1 and type 2 diabetes.1 The problem is not that education itself is ineffective but in the design and delivery of such trials. For instance, …
Insulin Resistance in Essential Hypertension
Authors: Eleuterio Ferrannini, Giuseppe Buzzigoli, Riccardo Bonadonna, Maria Antonietta Giorico, Marco Oleggini, Linda Graziadei, Roberto Pedrinelli, Luigi Brandi, Stefano Bevilacqua
Journal: New England Journal of Medicine (1987)

High blood pressure is prevalent in obesity and in diabetes, both conditions with insulin resistance. To test whether hypertension is associated with insulin resistance independently of obesity and glucose intolerance, we measured insulin sensitivity (using the euglycemic insulin-clamp technique), glucose turnover (using [3H]glucose isotope dilution), and whole-body glucose oxidation (using indirect calorimetry) in 13 young subjects (38 +/- 2 years [+/- SEM]) with untreated essential hypertension (165 +/- 6/112 +/- 3 mm Hg), normal body weight, and normal glucose tolerance. In the postabsorptive state, all measures of glucose metabolism were normal. During steady-state euglycemic hyperinsulinemia (about 60 microU per milliliter), hepatic glucose production and lipolysis were effectively suppressed, and glucose oxidation and potassium disposal were normally stimulated. However, total insulin-induced glucose uptake was markedly impaired (3.80 +/- 0.32 vs. 6.31 +/- 0.42 mg per minute per kilogram of body weight in 11 age- and weight-matched controls, P less than 0.001). Thus, reduced nonoxidative glucose disposal (glycogen synthesis and glycolysis) accounted for virtually all the defect in overall glucose uptake (1.19 +/- 0.24 vs. 3.34 +/- 0.44 mg per minute per kilogram, P less than 0.001). Total glucose uptake was inversely related to systolic or mean blood pressure (r = 0.76 for both, P less than 0.001). These results provide preliminary evidence that essential hypertension is an insulin-resistant state. We conclude that this insulin resistance involves glucose but not lipid or potassium metabolism, is located in peripheral tissues but not the liver, is limited to nonoxidative pathways of intracellular glucose disposal, and is directly correlated with the severity of hypertension.
AB0892 Evaluation of Thyroid Function in Children with Familial Mediterranean Fever
Authors: F. Dortbas, F. Kilicbay, N. Cebeci, O. Tufekci, E. Comak, E. Melek
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Familial Mediterranean fever (FMF) is the most frequent hereditary autoinflammatory disease, characterized by recurrent self-limited attacks of fever and polyserositis. The development of renal amyloidosis type AA is the most devastating manifestation of the disease. Apart from major target organs as renal, cardiovascular, respiratory and gastrointestinal system, endocrine organs can also be involved. Yet, it is unclear how FMF affects thyroid function in patients that are not complicated with amyloidosis. <h3>Objectives</h3> The aim of this study was to evaluate the thyroid function in children with FMF that are not complicated with amyloidosis. <h3>Methods</h3> A cross-sectional study was carried out in pediatric rheumatology outpatient clinics. The medical records of patients with FMF were reviewed. Demographic characteristics, disease duration, mutation analysis, clinical findings, free T3, free T4, TSH were all noted at attack free periods. <h3>Results</h3> A total of 82 children, 42 girls (51.2%), with a mean age of 7.76±3.76 years at diagnosis and disease duration 22.31±24.42months, were included. Twenty one (25.6%) patients were found to have parental consanguinity and 31 (37.8%) patients had family history of FMF. Twelve (14.6%) patients were homozygous, 25 (30.5%) patients were compound heterozygous and 34 (41.5%) patients were heterozygous for MEFV gene. Eleven (13.4%) patients had complex allele mutations (≥3 mutations). Colchicine treatment was started in all patients. The dosage of colchicine needed to control the disease symptoms was 0.95±0.31 mg/day. The mean serum free T3, free T4 and TSH levels of patients were 3.96±0.54 pg/ml, 1.15±0.15 ng/ml, and 2.53±2.25 micU/ml, respectively. Hypothyroidism requiring levothyroxine treatment was found in 2 patients (2.43%) at the time of the study and one patient was found to have subclinical hypothyroidism. <h3>Conclusions</h3> Although an association of hypothyroidsim and FMF has been reported before we did not find an increase prevalance of thyroid function abnormalities in children with FMF who are not complicated with amyloidosis. Our results suggest that thyroid function tests don9t need to be screened routinely in FMF patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5111
Engineering Periodic shRNA for Enhanced Silencing Efficacy
Authors: Connie Wu, Kevin E Shopsowitz, Paula T Hammond
Journal: Molecular Therapy (2016)

RNA interference (RNAi) provides a versatile therapeutic approach via silencing of specific genes, particularly undruggable targets in cancer and other diseases. However, challenges in the delivery of small interfering RNA (siRNA) have hampered clinical translation. Polymeric or periodic short hairpin RNAs (p-shRNAs)-synthesized by enzymatic amplification of circular DNA-are a recent development that can potentially address these delivery barriers by showing improved stability and complexation to enable nanoparticle packaging. Here, we modify these biomacromolecules via structural and sequence engineering coupled with selective enzymatic digestion to generate an open-ended p-shRNA (op-shRNA) that is cleaved over ten times more efficiently to yield siRNA. The op-shRNA induces considerably greater gene silencing than p-shRNA in multiple cancer cell lines up to 9 days. Furthermore, its high valency and flexibility dramatically improve complexation with a low molecular weight polycation compared to monomeric siRNA. Thus, op-shRNA provides an RNAi platform that can potentially be packaged and efficiently delivered to disease sites with higher therapeutic efficacy.
Desmosomal genodermatoses
Authors: G. Petrof, J.E. Mellerio, J.A. McGrath
Journal: British Journal of Dermatology (2011)

Desmosomes are intercellular junctions that contribute to cell-cell adhesion, signalling, development and differentiation in various tissues, including the skin. Composed of a network of transmembranous and intracellular plaque proteins, pathogenic autosomal dominant or recessive mutations have been reported in 10 different desmosomal genes, resulting in a spectrum of phenotypes variably affecting skin, hair and heart. This review summarizes the molecular pathology and phenotypes that predominantly affect the skin/hair. Recent desmosomal genodermatoses described include lethal congenital epidermolysis bullosa (plakoglobin), cardiomyopathy with alopecia and palmoplantar keratoderma (plakoglobin), hypotrichosis with scalp vesicles (desmocollin 3), and generalized peeling skin disease (corneodesmosin). Understanding the range of clinical phenotypes in combination with knowledge of the inherent desmosome gene mutation(s) is helpful in managing and counselling patients, as well as providing insight into the biological function of specific components of desmosomes in skin and other tissues.
Hemorrhage from the Gall Bladder
Authors: Perry B. Hudson, Peer P. Johnson
Journal: New England Journal of Medicine (1946)

The purpose of this paper is twofold — to present 4 cases of hemorrhage into or from the gall bladder, 3 of which had unusual features, and to show the significance of hemorrhage into the gastrointestinal tract in cases of cholelithiasis, as indicated by routine examination of the stools.Of the cases of massive hemorrhage from the gall bladder, 1 was due to neoplasm, so that the hemorrhage was not remarkable. The other 3 cases, however, are similar to the 24 already contained in the literature. This condition was first reported in 1892 by Naunyn,1 who described 3 cases of . . .
SAT0009 The Prevalence and Patterns of Antiphospholipid Antibodies in SLE and Non-Sle Patients with END Stage Renal Disease: Table 1
Authors: A. Broder, I. Blanco, C. Vila, C. Jonhston, J. Neugarten
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Elevated levels of antiphospholipid antibodies (aPL Abs) have been reported in over 30% of lupus (SLE) patients, and are associated with an increased risk of thrombosis. However, not all aPL Abs are pathogenic, and some may reflect chronic endothelial damage seen in chronic diseases, including cardiovascular disease and end stage renal disease (ESRD). Indeed, some studies reported the prevalence of aPL Abs as high as 30% in ESRD patients. The significance of these antibodies in ESRD remains controversial, but may be associated with an increased risk of thrombotic complications and cardiovascular mortality in these patients. Surprisingly, no studies to date ascertain the frequency of aPL Abs in SLE patients with ESRD. <h3>Objectives</h3> To compare the frequency of elevated aPL Ab levels in SLE and non-SLE patients with ESRD from a large urban tertiary care center. We hypothesized that SLE patients will have a higher prevalence and a different pattern of aPL Abs compared with non-SLE ESRD patients. <h3>Methods</h3> We identified all patients with ESRD at our center who had aPL Abs measured between 2005 and 2012. SLE was defined using ICD9 (International Classification of Disease) code (710.0). We also determined the prevalence of aPL Abs in a subgroup of patients who fulfilled the American College of Rheumatology criteria for SLE and had a history of biopsy proven lupus nephritis. IgA, IgG, and IgM isotypes were measured for the following aPL Abs: anticardiolipin (aCL), anti-beta2 glycoprotein I (anti-B2GPI), and antiphosphatidylserine (aPS). Positivity was defined as ≥20IU ("laboratory criteria"), and ≥40IU ("clinical criteria"). We used Fisher exact test to compare the frequencies of aPL Abs between non-SLE, SLE by ICD9 and SLE by ACR criteria vs. non-SLE. <h3>Results</h3> We identified 116 non-SLE ESRD with aPL Abs measured, and 61 SLE ESRD with aPL Abs. Of the 61 SLE patients, 21 met ACR criteria for SLE and had biopsy proven lupus nephritis. The frequencies of aPl Abs are presented in Table 1. The prevalence of medium/high aPL Abs &gt;40 IU was under 10% in both SLE and non-SLE ESRD. However, the prevalence and aPL Ab patterns were different among SLE and non-SLE patients. <h3>Conclusions</h3> This is the first study to compare the prevalence of 3 aPL Ab types in SLE and non-SLE ESRD. Our data suggest that the overall prevalence of aPL Abs is higher in SLE than in non-SLE ESRD. The implications for thrombotic complications in SLE ESRD compared to non-SLE ESRD deserve further investigation. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4818
Ligation of the Inferior Vena Cava or Iliac Veins
Authors: William R. Moses
Journal: New England Journal of Medicine (1946)

THE first ligations of the inferior vena cava were performed by Kocher in 1883 and Billroth in 1885,1 these procedures being the results of operative trauma and both being followed by a fatal outcome. The first successful ligation was performed by Bottini.2 Two ligations of this type were performed in 1906 and a third in 1910 by Trendelenburg,3 , 4 all for thrombophlebitis of the pelvic vein with septicemia, 1 patient recovering. Martens5 has reported 2 cases of ligation of the vena cava and 9 of the iliac vein for thrombophlebitic pyemia, 7 of the 11 patients surviving. Krotoski,6 summarizing the literature . . .
Retention of asbestos fibers in the human body.
Authors: A Tossavainen, A Karjalainen, P J Karhunen
Journal: Environmental Health Perspectives (1994)

The number, type, and size of retained asbestos fibers were measured by scanning electron microscopy (SEM) in lung tissues of 10 workers who had died from lung cancer or mesothelioma. The levels were 190-3000 x 10(6) fibers/g of dry tissue in three crocidolite sprayers, 6-39 x 10(6) fibers/g of dry tissue in two asbestos product workers and 13-280 x 10(6) fibers/g of dry tissue in five insulators exposed to anthophyllite. The duration of past exposure corresponding to the limit of 1 million fibers/g of dry tissue was 1 to 2 days in spraying, 3 to 10 days at the production plant and 1 to 4 months in insulation work. No long-term clearance of amphibole fibers, > 5 microns in length, could be demonstrated. In one of the sprayers the fiber concentrations of lung parenchyma, visceral and parietal pleura, hilar lymph nodes, and kidney cortex were orders of magnitude higher than in a series of unselected autopsies. The size and aspect ratio of crocidolite fibers in various tissues were similar, indicating that the translocation processes are rather unselective in respect to fiber dimensions.
Scintigraphic Findings of Epidermoid Carcinoma Mimicking Findings of Malignant Otitis Externa
Authors: WAN-YU LIN, SHYH-JEN WANG, SHIN-HWA YEH
Journal: Clinical Nuclear Medicine (1996)

A 62-year-old man had a 2-year history of discharge from the left ear and a 2-day history of left otalgia. He had diabetes mellitus for more than 30 years, which was under regular treatment. Examination revealed erythematous swelling, granulation tissue, and discharge in the left acoustic canal. Malignant otitis externa was suspected. Tc-99m MDP bone and gallium imaging were compatible with malignant otitis externa. However, his condition didn't improve under medical treatment. A biopsy showed epidermoid carcinoma from the left ear.
Novel roles of a transcription elongation regulator in mammary gland development and tumorigenesis.
Authors: N Sreejith Janardhanan, J Sun, A Amleh, L Sun, L Wang, R Li
Journal: Cancer Research (2009)

Abstract Abstract #6013 Historically, transcriptional regulation in mammary gland development and breast cancer development is thought to primarily occur at the stage of transcription initiation. However, recent studies of genome-wide transcription suggest that the majority of “inactive” genes in human cells experience transcription initiation and many of them have binding of RNA polymerase at the promoter-proximal region. Thus, transcription elongation may represent a widespread, yet vastly under-appreciated step for mammalian gene regulation. Cofactor of BRCA1 (COBRA1), which was first identified as a BRCA1-binding protein, acts as an integral subunit of the negative elongation factor (NELF) complex to stall RNA polymerase II (RNAPII) during estrogen-stimulated transcription elongation. COBRA1 also shares a number of target genes for transcriptional regulation with BRCA1 in breast cancer cells. In support of its potential role in tumor suppression, COBRA1 is preferentially expressed in luminal epithelial cells in normal mammary ducts; and its reduced expression is strongly correlated with metastatic breast cancer. Knockdown of COBRA1 leads to elevated hormone-dependent transcription and accelerated cell proliferation in vitro. To further investigate the biological function of COBRA1, we compared tumor growth of control and COBRA1 knockdown human breast cancer cells in a xenograft mouse model. In contrast to tumors from the control cells whose growth was strictly estrogen-dependent, tumors from COBRA1-depleted cells achieved sustained growth even in the absence of exogenously added estrogen. This result suggests that depletion of COBRA1 either allows hormone-independent cell proliferation or sensitizes cells to grow under extremely low levels of estrogen. In a complementary approach, a Cre-lox system was used to delete mouse Cobra1 in whole body or in mammary gland. Mouse embryos deficient in Cobra1 do not develop beyond E5.5; and mammary gland-specific Cobra1 knockout mice exhibit severe defects in alveologenesis and lactogenesis. The molecular basis for the Cobra1-associated developmental defects and the possible impact of Cobra1 deletion on mammary tumorigenesis will be discussed. By linking regulation of transcription elongation with mammary gland-specific functions, our work establishes a novel paradigm for gene regulation in mammary gland biology and breast cancer research. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6013.
Case 27-2008
Authors: Theodore I. Steinman, Anthony E. Samir, Lynn D. Cornell
Journal: New England Journal of Medicine (2008)

A 64-year-old man was admitted to the hospital because of abdominal pain, nausea, and an elevated serum creatinine level. He had a history of recurrent epigastric pain, which had been attributed to pancreatitis and gastroesophageal reflux disease. One week before admission, epigastric pain recurred, with nausea and vomiting; 3 days before admission, he stopped all oral intake, but symptoms worsened. On admission, the serum creatinine level was 3.5 mg per deciliter, and the urea nitrogen level was 28 mg per deciliter. Intravenous fluids were administered, without improvement. A diagnostic procedure was performed.
Abstract 5420: Normal mammary epithelial mitochondria introduced into human breast cancer cells results in inhibition of proliferation and increased drug sensitivity of the MCF-7 breast cancer cell line.
Authors: Robert L. Elliott, Xian P. Jian, Jonathan F. Head
Journal: Cancer Research (2013)

Abstract Warburg in the 1920s postulated that mitochondrial dysfunction alters metabolism in cancer. He observed in cancer cells aerobic glycolysis, which is the conversion of glucose to lactic acid in the presence of oxygen, the so called “Warburg effect” [1]. Mitochondrial dysfunction of cancer cells includes increased aerobic glycolysis, elevated levels of ROS, decreased apoptosis, and resistance to chemotherapeutic agents. We reported on the ultrastructural observations of mitochondria in human breast carcinoma cells [2]. There were three distinct groups: (1) mitochondria absent, (2) mitochondria present, (3) mitochondria present but sparse and abnormal. Tumors in the absent group were more anaplastic, aggressive, and resistant to treatment. We hypothesized that the introduction of normal mitochondria into cancer cells might restore mitochondrial function and inhibit cancer cell growth, and reverse chemoresistance. First we tested if mitochondria of normal mammary epithelial MCF-12A cells could enter into cultured human cancer cells. Then we determined if introducing normal mitochondria into cancer cells would inhibit proliferation. Finally we determined if addition of normal mitochondria increases the sensitivity of human breast cancer MCF-7 cells to chemotherapy. We found JC-1 stained mitochondria from normal mammary epithelial MCF-12A cells can enter into the cancer cell lines MCF-7, MDA-MB-231, and NCI/ADR-Res, but cannot enter normal MCF-12 A cells. The normal mitochondria from normal MCF-12 A cells suppressed the proliferation of MCF-7 and NCI/ADR-Res cells in a dose dependent pattern, but did not affect the proliferation of normal MCF-12A cells. The normal mitochondria from normal MCF-12A cells increased the sensitivity of human breast cancer MCF-7 cells to doxorubicin, Abraxane, and carboplatin. In conclusion the introduction of normal mammary mitochondria into human cancer cells inhibits cancer cell proliferation and increases the sensitivity of the MCF-7 human breast cancer cells to doxorubicin, Abraxane, and carboplatin. This phenomenon has never been reported, and the results support the role of mitochondrial dysfunction in cancer and suggest the possible use of targeted mitochondria as an adjunct to cancer therapeutics. Citation Format: Robert L. Elliott, Xian P. Jian, Jonathan F. Head. Normal mammary epithelial mitochondria introduced into human breast cancer cells results in inhibition of proliferation and increased drug sensitivity of the MCF-7 breast cancer cell line. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5420. doi:10.1158/1538-7445.AM2013-5420