tbuckley/cabot-search huggingface dataset:
Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study
Authors: M. P. Ekstrom, A. Bornefalk-Hermansson, A. P. Abernethy, D. C. Currow
Journal: BMJ (2014)

<b>Objective</b> To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD). <b>Design</b> Population based longitudinal consecutive cohort study. <b>Setting</b> Centres prescribing long term oxygen therapy in Sweden. <b>Patients</b> 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register. <b>Main outcome measures</b> Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs. <b>Results</b> 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation. No patient was lost to follow-up. Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively. Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend. Opioids also had a dose response relation with mortality: lower dose opioids (≤30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44). Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99). Associations were not modified by being naive to the drugs or by hypercapnia. <b>Conclusions</b> Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease.
Mast cell tryptase potentiates histamine-induced contraction in human sensitized bronchus
Authors: PR Johnson, AJ Ammit, SM Carlin, CL Armour, GH Caughey, JL Black
Journal: European Respiratory Journal (1997)

The mast cell plays a pivotal role in the early asthmatic response via release of mediators, which directly influence airway smooth muscle tone. Canine mast cell tryptase has been reported to potentiate the contractile response of canine isolated airways to histamine. The aim of this study was to investigate whether human mast cell tryptase potentiated contractile responses in human isolated bronchi. The effect of tryptase differed according to the sensitization status of the bronchi. In lung tissue from sensitized patients (those whose bronchial tissue contracted in response to the application of any of four common antigens) 90 ng.mL-1 of human purified lung tryptase markedly potentiated the contractile response to histamine. The maximal response as a percentage of maximal contraction to acetylcholine was 80 +/- 8% in control tissues and 119 +/- 6% in tryptase treated tissues (n = 4; p &lt; 0.05). Tryptase, at a dose of 200 ng.mL-1, also potentiated responses but to a lesser degree, 100 +/- 5% (n = 4; p &lt; 0.05). In nonsensitized bronchi, neither 90 nor 200 ng.mL-1 tryptase had any significant effect on histamine responses. The increased response in the presence of tryptase in sensitized tissue was inhibited by the calcium voltage-dependent channel antagonist, verapamil (10(-6) M). We have shown, for the first time, that human mast cell tryptase potentiates contraction in sensitized bronchi via a calcium-related mechanism. These findings provide a link between a mast cell derived product and in vitro human airway hyperresponsiveness.
LYMPHOBLASTOMA WITH PARAPLEGIA AND PROLONGED IRRADIATION
Authors: L. F. Wheatley
Journal: JAMA (1935)

This case of lymphoblastoma (Hodgkin's type) is reported because of a number of points of unusual interest: certain neurologic and skin manifestations, its response to radiation therapy over a considerable period of time, and the changes found at autopsy. The patient first came under my observation at 12 years of age with a negative family history and negative past history until 9 years of age, when she had mumps in the left parotid gland. A year later there was an enlarged cervical gland on the same side, which was removed surgically. A year later there was a recurrence, which was again operated on. At this time it was considered tuberculous and the patient was referred to a tuberculosis sanatorium, where routine examination of the chest disclosed a large superior mediastinal growth, corresponding to Wessler's group I—expanding mediastinal tumor. A recurring cervical gland enlargement was excised at this time and microscopic examination showed it to be a slow
Detection and quantification of ploidy, nuclearity, and DNA synthesis in rat hepatocytes after administration of a peroxisome proliferator.
Authors: J A Styles
Journal: Environmental Health Perspectives (1993)

The peroxisome proliferator methylclofenapate (MCP) induces species-specific liver growth and cancer in rats and mice. The acute hyperplastic effects of MCP were studied in rats given MCP (25 mg/kg by daily gavage) and injected IP (0.5 mL, 50 mM) with bromodeoxyuridine (BrdU) 6 hr before each sampling time. The animals were killed at 6-hr intervals and hepatocyte suspensions prepared from their livers by collagenase perfusion. The cells were stained with propidium iodide (PI) and BrdU antibody combined with fluorescein isothiocyanate (FITC). DNA content (PI-red fluorescence) and S phase (BrdU/FITC-green fluorescence) were analyzed simultaneously by two-parameter flow cytometry and the frequency of S phase in different ploidy classes determined. At the same time, S-phase cells from different ploidy groups were sorted onto slides by fluorescence-activated cell sorting and examined microscopically to determine the frequency of binucleated cells undergoing DNA synthesis. The results show that MCP-induced acute hyperplasia occurs mainly in a sensitive subpopulation of binucleated hepatocytes.
Leukaemic macrocheilia in acute myeloblastic leukaemia
Authors: E. Jeong, H.J. Park, J.Y. Lee, B.K. Cho
Journal: British Journal of Dermatology (2004)

An 18‐year‐old woman presented with a 1‐month history of nonpitting oedema of both lips with tender crusted plaques. Initially, her lips were only swollen, but erosive lesions gradually developed, becoming crusted and firm (Fig. 1a). She had had mild intermittent fever for 3 months and gradual weight loss amounting to 11 kg. Histology showed a diffuse infiltrate of leukaemic cells in the dermis, extending into the subcutaneous fat (Fig. 2). The cells stained positively with chloroacetate esterase (Leder's) and lysozyme stain, which showed them to be of myeloid lineage. Bone marrow examination was diagnostic for acute myeloblastic leukaemia. She was treated with cytosine arabinoside, daunorubicin and prednisone as induction chemotherapy. Her lips were markedly improved after chemotherapy (Fig. 1b). Our case shows an uncommon manifestation of leukaemia cutis presenting as macrocheilia.
Abstract 1007: Nanoformulation enhances anti-angiogenic efficacy of Tunicamycin
Authors: Aditi Banerjee, Dipak K. Banerjee
Journal: Cancer Research (2014)

Abstract The breast cancer landscape indicates it is a global problem and accounts for nearly a quarter of all cancers in women. In 2008, 1.4 million women were diagnosed with the disease worldwide and 438,000 died globally in 2010. In the United States, it is estimated that 296,000 women and 2,240 men will be diagnosed with breast cancer in 2013 and 39,620 women and 410 men will die from the disease. In 2030, with no major changes in prevention or treatment 747,802 women are estimated to die worldwide. Breast cancer treatment includes surgery, radiation therapy, chemotherapy and/or hormonal therapy, and within the past 15 years, targeted antibody therapy. Unfortunately, de novo and acquired resistance are major issues with all known targeted therapies. Tumor microenvironment (TME) is immensely complex and contributes to chemoresistance. Using Tunicamycin, a potent inhibitor of asparagine-linked (N-linked) protein glycosylation we have established earlier that Tunicamycin inhibits (i) angiogenesis in vitro by arresting cells in G1; (ii) in vivo angiogenesis in Matrigel™ implant in nude mice; and (iii) prevents the progression of double- and triple-negative breast tumors in athymic nude mice by inducing “ER stress”. Nanoparticles (&amp;lt;100 nm) evade the immune system's clearing mechanisms long enough to reach the targeted disease tissue efficiently. We have, therefore, hypothesized that nano-formulated Tunicamycin would have a better efficacy in treating breast cancer in the clinic. The objective was to evaluate nano-formulated Tunicamycin, and we have used Tunicamycin encapsulated in peptide nanotubes, nanotubes bound to gold nanoparticles (Au NPs) conjugated with Tunicamycin, Tunicamycin conjugated with nanotubes, Au NPs bound to tubes and conjugated with Tunicamycin, and Au NPs conjugated with Tunicamycin. The MTT assay indicated that nanoparticles (1 μg/mL) inhibited capillary endothelial cells proliferation ∼50% within one hour of treatment whereas the native Tunicamycin had no effect. The nanoformulated Tunicamycin blocked the cell cycle progression by inhibiting either both cyclin D1 and CDK4, or cyclin D1, or the CDK4 expression as well as the expression of phospho Rb (serine-229/threonine-252). Phosphorylation of p53 at serine-392 was down-regulated but not the total p53. Increased expression of GRP-78/Bip identified “ER stress”. Upregulated expression (1.6-5.5 folds) of phopsho-PERK supported induction of unfolded protein response (upr) signaling. Down regulated expression of caspase-9 and caspase-3 proposes a non-canonical pathway of cell death during “ER stress” induced by nano-formulated Tunicamycin. Citation Format: Aditi Banerjee, Dipak K. Banerjee. Nanoformulation enhances anti-angiogenic efficacy of Tunicamycin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1007. doi:10.1158/1538-7445.AM2014-1007
Attenuated allergic airway inflammation in <i>Cd39</i> null mice
Authors: M. Idzko, C. K. Ayata, T. Müller, T. Dürk, M. Grimm, K. Baudiß, R. P. Vieira, S. Cicko, C. Boehlke, A. Zech, S. Sorichter, J. Pelletier, J. Sévigny, S. C. Robson
Journal: Allergy (2013)

Abstract Background Extracellular Adenosine‐5′‐Triphosphate ( ATP ) is known to accumulate in the lung, following allergen challenge, and contributes via activation of purinergic receptors on dendritic cells ( DC ), to the development of allergic airway inflammation ( AAI ). Extracellular ATP levels in the airways are normally tightly regulated by CD 39. This ectonucleotidase is highly expressed by DC purified from skin (Langerhans cells) and bone marrow, and has been shown to modulate DC adaptive/haptenic immune responses. In this study, we have evaluated the impact of Cd39 deletion and associated perturbation of purinergic signaling in AAI . Methods Standard ovalbumin ( OVA )–alum and house dust mite ( HDM ) bone marrow‐derived DC ( BMDC )‐dependent models of AAI were used to study effects of Cd39. Migration assays, time lapse microscopy, and T‐cell priming assays were further used to determine functional relevance of Cd39 expression on BMDC in the setting of immune and Th2‐mediated responses in these models. Results Cd39 −/− mice exhibited marked increases in BALF ATP levels but paradoxically exhibited limited AAI in both OVA –alum and HDM models. These pathophysiological abnormalities were associated with decreased myeloid DC activation and chemotaxis toward ATP , and were linked to purinergic receptor desensitization responses. Further, Cd39 −/− DC s exhibited limited capacity to both prime Th2 responses and form stable immune synaptic interactions with OVA ‐transgenic naïve T cells. Conclusions Cd39 ‐deficient DC s exhibit limited capacity to induce Th2 immunity in a DC ‐driven model of AAI in vivo . Our data demonstrate a role of CD 39 and perturbed purinergic signaling in models of AAI .
Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation
Authors: Lisbeth F. A. Maurissen, M. Christella L. G. D. Thomassen, Gerry A. F. Nicolaes, Björn Dahlbäck, Guido Tans, Jan Rosing, Tilman M. Hackeng
Journal: Blood (2007)
MODULATION OF CARDIAC REMODELING AFTER CHRONIC ISCHEMIA BY LECTIN-LIKE OXIDIZED LOW-DENSITY LIPOPROTEIN RECEPTOR-1 DELETION
Authors: Jingjun Lu, Wenze Wang, Harish Muniyappa, Xianwei Wang, Sona Mitra, Bobby Long, Kumuda C. Das, Bum-Yong Kang, Muhammad R. Marwali, Changping Hu, Magomed Khaidakov, Jawahar L. Mehta
Journal: Journal of the American College of Cardiology (2011)
A Randomised, Prospective Study Comparing Two Contrast Media in ERCP
Authors: W. J. Cunliffe, I. Cobden, M. I. Lavelle, R. Lendrum, N. P. Tait, C. W. Venables
Journal: Endoscopy (1987)

A randomised, prospective, stratified, double blind study comparing two contrast media in endoscopic retrograde cholangio-pancreatography (ERCP) was undertaken. Forty-six patients received Meglumine/Sodium loxaglate (Hexabrix 320) and forty-eight received Meglumine/Sodium Diatrizoate (Urografin 310).
Osteoarthritis: Diagnosis and Medical/Surgical Management
Authors: Thomas G. Benedek
Journal: JAMA (1992)

The second edition of this well-regarded monograph appears eight years after the first. Expanded by 30%, it presents a comprehensive, current exposition of the various biologic processes, clinical manifestations, and therapies that pertain to the rather overly inclusive diagnosis of osteoarthritis. Of the 50 contributors, 30 are new to this edition; 25 are orthopedic surgeons and 15 are rheumatologists. Each of the four sections— basic considerations, general aspects of diagnosis, general aspects of management, and regional considerations—has the same editor as in the previous edition. Whether osteoarthritis is "primary," due to a genetic or unidentified cause, or secondary to trauma or a specific disease, it is primarily an affection of articular cartilage. Therefore, seven chapters are devoted to an exhaustive and lucid consideration of all aspects of this tissue. These chapters are products of extensive collaboration between basic scientists and clinicians. The section itself has been enlarged from 25% to
Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor
Authors: Donghui Zhu, Yaoming Wang, Itender Singh, Robert D. Bell, Rashid Deane, Zhihui Zhong, Abhay Sagare, Ethan A. Winkler, Berislav V. Zlokovic
Journal: Blood (2010)
Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures
Authors: David Garcia, John H. Alexander, Lars Wallentin, Daniel M. Wojdyla, Laine Thomas, Michael Hanna, Sana M. Al-Khatib, Paul Dorian, Jack Ansell, Patrick Commerford, Greg Flaker, Fernando Lanas, Dragos Vinereanu, Denis Xavier, Elaine M. Hylek, Claes Held, Freek W. A. Verheugt, Christopher B. Granger, Renato D. Lopes
Journal: Blood (2014)
Case of Diabetes Mellitus Treated by the Sole Administration of Skimmed Milk: Death
Authors: H. Chaldecott
Journal: BMJ (1875)

and the obturator intervenes muscle.On withdrawing it, it was found to be congested, but wvith its covering peritoneum still shining and intact.In Case III, the operation succeeded in curing the inguinal hernia; but the dissection of the femoral hernia wvas so instructive, that it will repay our attention, and consoled me for one of the most disagreeable post nmortemz examinations I ever saw.,, 14
ANTIGENIC RELATIONSHIPS BETWEEN IMMUNE GLOBULINS AND CERTAIN RELATED PARAPROTEINS IN MAN
Authors: Edward C. Franklin, Denis R. Stanworth
Journal: The Journal of Experimental Medicine (1961)

The antigenic properties of normal 19S gamma-globulin, pathologic macroglobulins, beta(2A)-myeloma proteins, and Bence Jones proteins have been compared with 7S gamma-globulin and the small 3.5S units derived from it by gel diffusion precipitin techniques. These studies demonstrate that the determinant groups on the 7S gamma-globulin molecule responsible for the cross-reaction with each of the other proteins are associated with the two fragments of 7S gamma-globulin which have the antibody-combining sites. The antigenic specificity of the 7S gamma-globulin which distinguishes it from each of these proteins is associated primarily with the fragment that is richest in hexose and can not combine with antigen. However when compared with certain of the paraproteins additional antigenic specificity was also found to reside in the fragments with antibody-combining activity. The finding of similar antigenic relationships in rabbit gamma-globulins suggests that some of the biological properties associated only with the 7S gamma-globulins and not with the other immune globulins may reside in the fragment which also carries the antigenic specificity of the protein.
A midline neck lump in a child
Authors: I. C. C. King, N. A. Brierley, K. Erdinger
Journal: BMJ (2013)

An 11 year old girl presented with a six month history of a swelling in the midline of her neck, overlying her hyoid bone. Three weeks previously, the skin overlying the swelling had broken down and the area had bled and been painful ever since. She was fit and well and denied trauma to the area. She was taking no drugs and reported no allergies. Her maternal grandmother had a multinodular goitre removed when she was 30 years of age.

Examination showed a bright red exophytic lesion with a diameter of 7 mm in the midline of her neck (figure⇓). The lump moved upwards when she protruded her tongue. Intraoral examination was grossly normal. There was no palpable lymphadenopathy.





### 1 What are the differential diagnoses for this lesion?

#### Short answer

The main causes of a midline swelling of the neck in a child are congenital abnormalities (thyroglossal cysts, ranulas, ectopic thyroid cysts, dermoid cysts), infection (abscess), trauma (pyogenic granulomas), cancer (lymphoma, lymphadenopathy), and vascular abnormalities (haemangioma, lymphangioma).

#### Long answer

Thyroglossal cysts account for about 75% of congenital midline swellings in childhood,1 2 and they are the most common abnormality of the midline neck seen in children.2 3 4 Most present by age 5 years …
Fibrinolysis in Cholestatic Jaundice
Authors: A. Jedrychowski, P. Hillenbrand, A. B. Ajdukiewicz, S. P. Parbhoo, S. Sherlock
Journal: BMJ (1973)

The fibrinolytic system was studied in primary biliary cirrhosis (16 patients) and large bile duct obstruction (10 patients, nine of whom had carcinoma). Plasma fibrinolysis (plasminogen activator activity) was decreased and fibrinogen increased in both groups of patients, particularly in those with large duct obstruction. These changes were related to the degree of cholestasis. Plasminogen activator activity was inversely related to serum triglyceride levels in patients with primary biliary cirrhosis. Urokinase inhibitors were decreased in both groups and antiplasmins increased in patients with large duct obstruction; fibrin/fibrinogen degradation products were normal in primary biliary cirrhosis and moderately increased in large duct obstruction. None of these fibrinolytic indices was related to the degree of cholestasis. Fibrinolytic activity and fibrinogen returned almost to normal levels after palliative surgery in the three patients with large duct obstruction who were studied. The decreased plasma fibrinolysis and increased fibrinogen may be due to altered lipid metabolism in cholestatic jaundice. In patients undergoing surgery for large duct obstruction there may be an increased risk of thrombosis.
Intramuscular Metastasis of Uterine Cervix Cancer on F-18 FDG PET/CT
Authors: Il Ki Hong, Deog Yoon Kim
Journal: Clinical Nuclear Medicine (2011)

We report F-18 FDG PET/CT images of biopsy-proven intramuscular metastasis from primary uterine cervix cancer. A 70-year-old woman was admitted because of a mass in the left axilla. She was diagnosed with uterine cervix cancer and underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection and received adjuvant chemotherapy and radiation therapy 9 years ago. Magnetic resonance imaging showed a large soft tissue mass in the intramuscular region of the left axilla. The mass showed intense F-18 FDG uptake with a central necrotic portion on F-18 FDG PET/CT. Hypermetabolic lymph nodes were also noted in the left axilla, interpectoral, and left supraclavicular areas. Additionally, several hypermetabolic nodules were noted in both lungs. The lesion in the left axilla was excised and the pathologic results were consistent with metastasis from uterine cervix cancer.
Keratoderma hereditarium mutilans (Vohwinkel's syndrome) associated with congenital deaf-mutism
Authors: K. PERIS, E.F. SALVATI, G. TORLONE, S. CHIMENTI
Journal: British Journal of Dermatology (2006)

Journal Article Keratoderma hereditarium mutilans (Vohwinkel's syndrome) associated with congenital deaf‐mutism Get access K. PERIS, K. PERIS Department of Dermatology, University of L'Aquila, Via Vetoio, 67010 L'Aquila, Italy Search for other works by this author on: Oxford Academic Google Scholar E.F. SALVATI, E.F. SALVATI Department of Dermatology, University of L'Aquila, Via Vetoio, 67010 L'Aquila, Italy Search for other works by this author on: Oxford Academic Google Scholar G. TORLONE, G. TORLONE Department of Dermatology, University of L'Aquila, Via Vetoio, 67010 L'Aquila, Italy Search for other works by this author on: Oxford Academic Google Scholar S. CHIMENTI S. CHIMENTI Department of Dermatology, University of L'Aquila, Via Vetoio, 67010 L'Aquila, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 132, Issue 4, 1 April 1995, Pages 617–620, https://doi.org/10.1111/j.1365-2133.1995.tb08721.x Published: 01 April 1995 Article history Accepted: 16 June 1994 Published: 01 April 1995
Peter John Mowbray
Authors: D. MOWBRAY
Journal: BMJ (2003)

Former geriatrician Corner Brook, Newfoundland (b Newcastle upon Tyne 1941; q Durham 1964; FCFPC), died from a brain haemorrhage on 24 August 2003.

Peter Mowbray emigrated to Newfoundland in 1968, where he joined a practice in Corner Brook. He later specialised in geriatric medicine, joining the staff of Memorial Hospital, Corner Brook. For almost one third of his life he was dogged by the effects of brain haemorrhages. In 1995 he was forced to retire and later settled in Calgary close to his own and extended family. He leaves a wife, Eve; three children; and a grandchild.
Using Cost-Effectiveness Analysis to Improve Health Care: Opportunities and Barriers
Authors: Ray Moynihan
Journal: BMJ (2005)

J ust when you thought it was safe to dismiss cost effectiveness analysis as another dry and boring topic, of interest only to geeky economists or hard hearted bureaucrats, a book has emerged that makes the subject unexpectedly compelling. Peter J Neumann Oxford University Press, £21.50, pp 224 ISBN 0 19 517186 1 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> ![Graphic][4]</img> ![Graphic][5]</img> The Harvard academic Peter Neumann passionately and eloquently articulates why we should all take more of an interest in how our health system gets value for money from medical treatments and technologies. More importantly it … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif [5]: /embed/inline-graphic-5.gif