tbuckley/cabot-search huggingface dataset:
Recent advances: Control of chronic pain
Authors: T J Nurmikko, T P Nash, J R Wiles
Journal: BMJ (1998)

The most important clinical development in chronic pain during the past decade has not been new treatments but a thoroughly revised interpretation of the mechanisms that act to maintain pain. Pain is no more seen as a predetermined result of simple activation of certain neural structures. It is now understood to be a dynamic phenomenon due to myriad pathophysiological changes in the peripheral and central nervous system in response to disease, injury, or loss of function1 (box 1). These changes reflect the surprising but indisputable fact that the human nervous system is adaptable and capable of substantial plasticity. Initially reversible, the changes tend to become fixed depending on the nature and duration of the original cause, as well as the age and perhaps the genetic susceptibility of the patient

In chronic pain the abnormal activity in the altered pain mediating afferent system continues irrespective of its original causation. Simple blocking or severing of neural pathways is not helpful: the locus of abnormal barrages is simply shifted more centrally. Recent advances in the pharmacology of pain have unravelled some of the mediators of chronic pain, and they offer potential targets for treatments that are currently being developed (box 2). New investigative techniques are also being developed for improved detection of factors maintaining chronic pain. Alongside pharmacological advances, stimulation treatments and psychological approaches have seen innovative developments.

### Recent advances

Chronic pain is now known to be maintained by several pathophysiological mechanisms which currently can be dealt with only partially

New generation non-steroidal anti-inflammatory drugs have been developed for the treatment of rheumatic pain, but their true potential awaits the test of time

Choices for the treatment of neuropathic pain have increased with the advent of new anticonvulsants and topical agents

Indications for spinal cord stimulation have widened and include chronic angina and peripheral …
Countries with better health systems have better football teams
Authors: Roger Dobson
Journal: BMJ (2003)

When Bill Shankley, past manager of Liverpool Football Club, famously remarked that “some people think football is a matter of life and death … I can assure them it is much more serious than that,” he might just have had a point.

New research has found a link between the health system of a nation and the performance of its soccer team.

If a national team does well, according to the data, the country is also likely to …
The side effects of “P4P”
Authors: Douglas Kamerow
Journal: BMJ (2007)

General practitioners in the United Kingdom are now three years into an ambitious quality improvement program called the quality and outcomes framework. Under this program, they receive financial rewards when they meet specified targets in delivering preventive care and treatments to their patients. Several studies have documented that the targeted services have increased in response to this “pay for performance” program. In a qualitative ethnographic study, Ruth McDonald and colleagues observed and questioned office staff in two general practices to better …
Minimising bruising in the antecubital fossa after venepuncture.
Authors: A Dyson, D Bogod
Journal: BMJ (1987)

This plus the immediacy of the reaction suggest that his death was unlikely to have been due to toxicity.Nebulised lignocaine may cause narrowing of the airways in patients with asthma,2 but this is rarely of clinical importance especially as nebulised bronchodilators are given before fibreoptic bronchoscopy.Hypersensitivity to lignocaine is uncommon.Urticarial reactions may occur,3 and deaths due to anaphylaxis after small doses of injected local anaesthetic have been reported.45We believe that this is the first reported death due to topical lignocaine during fibreoptic bronchoscopy.This procedure, however, remains safe with few complications.
(28) Primary biliary cirrhosis with unusual vascular skin changes
Authors: R.R.M. Harman
Journal: British Journal of Dermatology (1977)

Journal Article (28) Primary biliary cirrhosis with unusual vascular skin changes Get access R.R.M. Harman R.R.M. Harman Weston‐super‐Mare General Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 97, Issue s15, 1 December 1977, Pages 62–64, https://doi.org/10.1111/j.1365-2133.1977.tb14336.x Published: 01 December 1977
Association of hyperglycaemia with hyponatraemia
Authors: I J Gordon
Journal: BMJ (1984)

perform a similar study of patients with Crohn's disease.Twenty two consecutive patients with Crohn's disease (11 men, 11 women, mean age 42, range 19-83) attending an outpatient clinic were studied.The Crohn's disease had been present from one month to 22 years (mean 61 years), and a disease activity index' at the time of study was 0-15 (mean 4).A random urine sample was collected, and urinary cc, microglobulin concentration measured by single radial immunodiffusion with the results corrected for urinary creatinine concentration and expressed as mg/g creatinine.Albustix testing was negative, and plasma creatinine concentrations were normal in all patients.Urine cx, microglobulin concentration was increased in 10 patients (> 10 mg/g creatinine) (mean (SD) 37 6 (26) mg/g; range 11-7- 86 mg/g).
Modification of gene expression: Help to detect doping with erythropoiesis‐stimulating agents
Authors: Emmanuelle Varlet‐Marie, Michel Audran, Michael Ashenden, Marie‐Thérèse Sicart, David Piquemal
Journal: American Journal of Hematology (2009)

Additional Supporting Information may be found in the online version of this article. ( www.skuldtech.com/ESA ) Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The G Protein–Gated Potassium Current <i>I</i> <sub>K,ACh</sub> Is Constitutively Active in Patients With Chronic Atrial Fibrillation
Authors: D. Dobrev, A. Friedrich, N. Voigt, N. Jost, E. Wettwer, T. Christ, M. Knaut, U. Ravens
Journal: Circulation (2005)

Background— The molecular mechanism of increased background inward rectifier current ( I K1 ) in atrial fibrillation (AF) is not fully understood. We tested whether constitutively active acetylcholine (ACh)-activated I K,ACh contributes to enhanced basal conductance in chronic AF (cAF). Methods and Results— Whole-cell and single-channel currents were measured with standard voltage-clamp techniques in atrial myocytes from patients with sinus rhythm (SR) and cAF. The selective I K,ACh blocker tertiapin was used for inhibition of I K,ACh . Whole-cell basal current was larger in cAF than in SR, whereas carbachol (CCh)-activated I K,ACh was lower in cAF than in SR. Tertiapin (0.1 to 100 nmol/L) reduced I K,ACh in a concentration-dependent manner with greater potency in cAF than in SR (−logIC 50 : 9.1 versus 8.2; P &lt;0.05). Basal current contained a tertiapin-sensitive component that was larger in cAF than in SR (tertiapin [10 nmol/L]-sensitive current at −100 mV: cAF, −6.7±1.2 pA/pF, n=16/5 [myocytes/patients] versus SR, −1.7±0.5 pA/pF, n=24/8), suggesting contribution of constitutively active I K,ACh to basal current. In single-channel recordings, constitutively active I K,ACh was prominent in cAF but not in SR (channel open probability: cAF, 5.4±0.7%, n=19/9 versus SR, 0.1±0.05%, n=16/9; P &lt;0.05). Moreover, I K1 channel open probability was higher in cAF than in SR (13.4±0.4%, n=19/9 versus 11.4±0.7%, n=16/9; P &lt;0.05) without changes in other channel characteristics. Conclusions— Our results demonstrate that larger basal inward rectifier K + current in cAF consists of increased I K1 activity and constitutively active I K,ACh . Blockade of I K,ACh may represent a new therapeutic target in AF.
Accuracy of Fine Needle Aspiration Cytology in the Pathological Typing of Non-small Cell Lung Cancer
Authors: Rita Nizzoli, Marcello Tiseo, Francesco Gelsomino, Marco Bartolotti, Maria Majori, Lilia Ferrari, Massimo De Filippo, Guido Rindi, Enrico Maria Silini, Annamaria Guazzi, Andrea Ardizzoni
Journal: Journal of Thoracic Oncology (2011)
Vitamin A absorption in cystic fibrosis: risk of hypervitaminosis A.
Authors: D R James, G Owen, I A Campbell, M C Goodchild
Journal: Gut (1992)

Vitamin A status was examined in nine adult cystic fibrosis patients and six adult control subjects, together with an assessment of their ability to absorb 10,000 IU of retinyl palmitate from a test meal, taken with appropriate pancreatic enzyme supplements. Median baseline values for plasma retinol and carotene, as well as median serum retinol binding protein concentrations, were significantly lower in cystic fibrosis patients than in control subjects. One cystic fibrosis patient had a raised fasting plasma retinyl ester concentration suggestive of chronic hypervitaminosis A, but no symptoms of toxicity. Measures of vitamin A absorption were also significantly lower in cystic fibrosis patients, although there was considerable overlap with control values. No correlation was observed between measures of baseline status and vitamin A absorption. Measurement of plasma retinyl esters may be an appropriate investigation in those patients considered to be at risk of chronic hypervitaminosis A.
Effects of menopause and nasal occlusion on breathing during sleep.
Authors: M A Carskadon, H M Bearpark, K M Sharkey, R P Millman, C Rosenberg, A Cavallo, C Carlisle, C Acebo
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Prevalence of sleep-disordered breathing (SDB) is reported to increase in menopausal women. We examined response to a nocturnal respiratory challenge (nasal occlusion) during overnight polysomnography in 31 women (45 to 55 yr). Thirteen were premenopausal, four perimenopausal, and 14 postmenopausal by history and hormonal assay. Nasal occlusion increased the apnea hypopnea index (AHI) (occlusion mean = 6.6 +/- 8.0 versus baseline mean = 1.6 +/- 2.6, p < 0.01) and arousal index (occlusion mean = 35.1 +/- 20.1 versus baseline mean = 20.7 +/- 11.6, p < 0.001), but did not change the oxygen saturation nadir in those with respiratory events (occlusion mean = 91.8 +/- 4.2 versus baseline mean = 92.0 +/- 11.6). Menopausal groups did not differ on AHI, arousal index, or oxygen saturation nadir in either condition. Key variables were compared between occlusion responders (n = 11) and nonresponders (n = 20). Responders and nonresponders were not distinguished by age, menopausal status, nor several cephalometric or anthropometric variables. Body mass index (31.1 +/- 8.5 versus 24.3 +/- 3.4, p < 0.003), neck circumference (34.0 +/- 2.5 versus 32.5 +/- 1.7 cm, p < 0.05), and mandibular-hyoid distance (18.5 +/- 3.8 versus 14.5 +/- 5.7 mm, p < 0.05) were greater in responders. These findings suggest hormonal factors may be less important than weight and facial morphology in midlife development of SDB in women.
Iron deficiency and Helicobacter pylori–induced gastric cancer: too little, too bad
Authors: Emad M. El-Omar
Journal: Journal of Clinical Investigation (2012)

Clinical vignette: A 38-year-old man consults you in the GI clinic because of frequent episodes of epigastric pain, nausea, and tiredness. His blood count shows signs of mild iron deficiency anemia. Upper GI endoscopy was normal, but antral and corpus biopsy specimens show evidence of gastric atrophy and Helicobacter pylori infection. Colonoscopy and capsule endoscopy showed no evidence of lesions in the large or small bowel. He receives a standard one-week course eradication therapy consisting of a proton pump inhibitor (PPI), amoxicillin, and clarithromycin. His symptoms improve, but his infection persists and he remains mildly anemic. He asks you whether the infection must be eradicated, as he read on the Internet that it can cause stomach cancer. He is also concerned about the anemia.
1306 URSODEOXYCHOLIC ACID NEUTRALIZES THE NOXIOUS EFFECTS OF LITHOCHOLIC ACID AND BILIRUBIN ON OSTEOBLASTS
Authors: M. Dubreuil, S. Ruiz-Gaspà, A. Martinez-Ferrer, A. Enjuanes, P. Peris, M.J. Martínez de Osaba, L. Alvarez, A. Monegal, A. Combalia, N. Guañabens, A. Pares
Journal: Journal of Hepatology (2011)
Immunofluorescent Studies in Adult Celiac Disease*
Authors: Walter Rubin, Anthony Stephen, Marvin H. Sleisenger, Graham H. Jeffries
Journal: Journal of Clinical Investigation (1965)

The etiology of childhood and adult celiac dis- ease is not known.It has been established, how- ever, that gluten, a complex heterogeneous pro- tein in wheat and other cereal grains, plays a significant role in the pathogenesis of the disease, and that the harmful factor resides in gliadin, the al- cohol soluble fraction of gluten (1-4).Treatment of celiac disease with a gluten-free diet results in clinical and biochemical improvement usually ac- companied by a decrease in the severity of the pathologic lesion in the proximal small intestinal mucosa.The ingestion of gluten by patients in remission on a gluten-free diet causes an exacerbation of symptoms, accompanied by malabsorption and acute inflammatory changes in the proximal jejunal mucosa (5).Furthermore, direct instil- lation of flour or gluten into the histologically normal distal small intestine of patients with adult celiac disease produces similar acute mucosal in- flammation (6), whereas the intestinal mucosa of a normal subject remains unchanged.The toxicity of gluten and gliadin is retained by mixtures of straight chain polypeptides that result from enzy- matic and chemical digestion of the protein (7-9).Further digestion of these toxic peptides by fresh extracts of hog small intestinal mucosa or by crude papain renders them inactive (7, 8).De- amidation or complete acid hydrolysis of gliadin also renders it inactive (1).
Reduction by Hyaluronidase of Myocardial Necrosis following Coronary Artery Occlusion
Authors: PETER R. MAROKO, PETER LIBBY, COLIN M. BLOOR, BURTON E. SOBEL, EUGENE BRAUNWALD
Journal: Circulation (1972)

Electrocardiographic, enzymatic, and morphologic signs of myocardial ischemic injury following coronary occlusion have previously been shown to be ameliorated by reducing myocardial oxygen requirements, and/or by increasing the availability of oxygen as well as of substrates for anaerobic ATP production. Since hyaluronidase increases diffusion through the extracellular space and may facilitate delivery of substrates to ischemic cells, the influence of its administration on the size of experimentally produced infarcts was studied. In 14 control dogs epicardial electrocardiograms were taken in 10-15 sites on the anterior surface of the left ventricle before and after occlusion of the left anterior descending coronary artery. Twenty-four hours later, transmural specimens were obtained from the same sites from which electrocardiograms had been recorded, and were analyzed for creatine phophokinase (CPK) activity, for histologic changes, and glycogen content. In control dogs, sites exhibiting S-T-segment elevation 15 min after occlusion showed early structural signs of necrosis and glycogen depletion in 97% of specimens taken after 24 hours. The relationship between S-T-segment elevation at 15 min (mv) and CPK activity 24 hours later (IU/mg protein) was log CPK = –0.061 S-T + 1.26. Hyaluronidase (225 u/kg) was given to 15 dogs; no hemodynamic changes occurred but the depression of CPK activity was reduced following occlusion; log CPK = –0.024 S-T + 1.28. Similarly, only 55% of sites that showed S-T-segment elevation prior to hyaluronidase administration exhibited histologic signs of early infarcts and glycogen depletion 24 hours later. It is concluded that hyaluronidase diminished myocardial necrosis following acute coronary occlusion.
Amphiphilic networks. VI. Swelling and sustained release of poly (N,N-dimethylacrylamide) -l-polyisobutylene, poly (N-N-dimethylamino ethylmethacrylate) -l-polyisobutylene and poly (2-hydroxyethyl methacrylate) -l-polyisobutylene networks
Authors: B. Keszler, J.P. Kennedy, P.W. Mackey
Journal: Journal of Controlled Release (1993)
Short Myelitis Lesions in Aquaporin-4-IgG–Positive Neuromyelitis Optica Spectrum Disorders
Authors: Eoin P. Flanagan, Brian G. Weinshenker, Karl N. Krecke, Vanda A. Lennon, Claudia F. Lucchinetti, Andrew McKeon, Dean M. Wingerchuk, Elizabeth A. Shuster, Yujuan Jiao, Erika S. Horta, Sean J. Pittock
Journal: JAMA Neurology (2014)

Short transverse myelitis (STM; <3 vertebral segments) is considered noncharacteristic of neuromyelitis optica (NMO) spectrum disorders (NMOSDs). Nonappreciation of the potential for STM to occur in NMOSD may lead to increased disability from delay in diagnosis and appropriate treatment.To determine the frequency of short lesions at the initial myelitis manifestation of NMOSD and to compare the demographic, clinical, and radiological characteristics of aquaporin-4-IgG (AQP4-IgG) seropositive and seronegative STM.We reviewed the records and images of patients at the Mayo Clinic who were identified as AQP4-IgG positive from 1996 to 2014. Inclusion criteria were first STM episode, magnetic resonance imaging performed 90 days or less from symptom onset, spinal cord T2-hyperintense lesion less than 3 vertebral segments, AQP4-IgG seropositivity, and a final diagnosis of NMO or NMOSD. Patients with an initial longitudinally extensive transverse myelitis were excluded (n = 151). Patients with STM who were seronegative for AQP4-IgG among an Olmsted County population-based cohort of inflammatory demyelinating disorders of the central nervous system were used as a control group.Delay to diagnosis in months, clinical and radiological characteristics, and disability measured by ambulatory status.Twenty-five patients who were AQP4-IgG seropositive with an initial STM represented 14% of initial myelitis episodes among patients with NMOSD. The STM episode was defined as the first manifestation of NMOSD in 10 patients (40%) preceded by optic neuritis in 13 patients (52%) and preceded by a nausea and vomiting episode in 2 patients (8%). In comparison with the excluded patients with NMOSD who had an initial longitudinally extensive transverse myelitis, delay to diagnosis/treatment was greater when initial lesions were short (P = .02). In AQP4-IgG-positive STM cases, subsequent myelitis episodes were longitudinally extensive in 92%. Attributes more common in patients with AQP4-IgG-positive STM than in 27 population-based patients with AQP4-IgG-negative STM included the following: nonwhite race/ethnicity; tonic spasms; coexisting autoimmunity; magnetic resonance imaging (central cord lesions, T1 hypointensity, and a brain inconsistent with multiple sclerosis); and cerebrospinal fluid (oligoclonal bands lacking).Short transverse myelitis is not uncommon in NMOSD and, when it is present, delays diagnosis and treatment. Clinical and radiological characteristics identified in this study may help select patients with STM who are at the highest risk for an NMOSD. Short transverse myelitis does not exclude consideration of AQP4-IgG testing or NMOSD diagnosis.
Finding the Evidence With Eponyms
Authors: Ajay Amarnani, Robert T. Brodell, Eliot N. Mostow
Journal: JAMA Dermatology (2013)

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Abstract 3168: Knock down of m-calpain in a mouse breast carcinoma cell line reduced tumor growth in mouse engraftment studies and compromises the Akt pathway and in vitro cell migration
Authors: Wai-chi Ho, Peter A. Greer
Journal: Cancer Research (2010)

Abstract Calpains are a family of calcium-dependent intracellular cysteine proteases consisting of fourteen members, with µ- and m-calpains (calpain 1 and 2) being ubiquitously expressed. Calpains play crucial roles in a various cellular functions including cell survival, movement and calcium homeostasis. Abnormal expression or activation of calpain is linked to pathological conditions such as neurodegenerative diseases, tumor growth and metastasis, platelet malfunction and muscular dysfunction. Studies have showed that calpain is involved in retraction of focal adhesions at the rear of migrating cells, indicating a major role of calpain in cell movement and cytoskeletal organization. In addition, calpain may be a key component in regulating cell survival and gene expression. We have examined the role of m-calpain in tumor growth. Mouse mammary carcinoma cells AC2M2 were transduced with a lentiviral vector expressing shRNA directed against m-calpain or a control shRNA. A mouse xenograft experiment was then carried out by injecting control cells or m-calpain knockdown cells into the mammary fat pads of nude mice. Preliminary results showed that mice injected with m-calpain knockdown cells grow smaller tumors. In vitro transwell migration assay showed that the m-calpain knockdown cells migrated slower than the control cells. Furthermore, biochemical studies demonstrated that these AC2M2 m-calpain knockdown cells have reduced activation of key the survival mediator Akt, although there was no significant difference in the growth rate between the knockdown and the control cells. Other biochemical studies implicate the transcription factor Foxo, a downstream target of Akt, in mediating the m-calpain-regulated tumor progression through activation of transcription of genes that are important in cell survival such as p27 Kip1 and Bim. In summary, our current data suggests that m-calpain mediates tumor growth through regulation of Akt signaling. This in turn regulates Foxo in the activation of gene transcription during cell survival signaling. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3168.