tbuckley/cabot-search huggingface dataset:
The cartoon in doctor-patient communication. Further study of the Arthritis and Rheumatism Council handbook on gout.
Authors: J M Moll, V Wright, M R Jeffrey, J D Goode, P M Humberstone
Journal: Annals of the Rheumatic Diseases (1977)

A sample of 50 consecutive patients with gout was tested by means of a multiple-choice knowledge-testing questionnaire based on the Arthritis and Rheumatism Council's Gout: A Handbook for Patients. Patients were divided into two groups: (a) those tested with an illustrated booklet containing 89 cartoons, and (b) those tested with an unillustrated booklet with text exactly the same as in the illustrated booklet. No significant difference was observed in either the overall test scores between the two groups or between individual question scores. It was concluded that increasing the number of illustrations in the Arthritis and Rheumatism Council's handbook on gout had not significantly increased the value of this material as a communication aid. Certain sources of error have been discussed including the possibility of an 'interest factor' due to the inevitable interest patients have in reading about their own disease, and also the possibility that technical factors to do with page layout and picture/text imbalance might be responsible for failing to show differences between the two groups.
Sacred Cows and Sympathetic Squirrels: The Importance of Biological Diversity to Human Health
Authors: Andy Dobson, Isabella Cattadori, Robert D Holt, Richard S Ostfeld, Felicia Keesing, Kristle Krichbaum, Jason R Rohr, Sarah E Perkins, Peter J Hudson
Journal: PLoS Medicine (2006)

Dobson and colleagues describe how some host species act to reduce the risk of transmission of virulent zoonotic pathogens to humans.
Calcium-sensing Receptor Attenuates AVP-induced Aquaporin-2 Expression via a Calmodulin-dependent Mechanism
Authors: Mauro Bustamante, Udo Hasler, Vale[Combining Acute Accent]rie Leroy, Sophie de Seigneux, Mitko Dimitrov, David Mordasini, Martine Rousselot, Pierre-Yves Martin, Eric Fe[Combining Acute Accent]raille
Journal: Journal of the American Society of Nephrology (2007)

Recent evidence suggests that arginine vasopressin (AVP)-dependent aquaporin-2 expression is modulated by the extracellular calcium-sensing receptor (CaSR) in principal cells of the collecting duct, but the signaling pathways mediating this effect are unknown. Using a mouse cortical collecting duct cell line (mpkCCD(cl4)), we found that increasing the concentration of apical extracellular calcium or treating with the CaSR agonists neomycin or Gd(3+) attenuated AVP-dependent accumulation of aquaporin-2 mRNA and protein; CaSR gene-silencing prevented this effect. Calcium reduced the AVP-induced accumulation of cAMP, but this did not occur by increased degradation of cAMP by phosphodiesterases or by direct inhibition of adenylate cyclase. Notably, the effect of extracellular calcium on AVP-dependent aquaporin-2 expression was prevented by inhibition of calmodulin. In summary, our results show that high concentrations of extracellular calcium attenuate AVP-induced aquaporin-2 expression by activating the CaSR and reducing coupling efficiency between V(2) receptor and adenylate cyclase via a calmodulin-dependent mechanism in cultured cortical collecting duct cells.
Cost-effectiveness analysis of sofosbuvir-based regimens for chronic hepatitis C
Authors: Ramón San Miguel, Vicente Gimeno-Ballester, Antonio Blázquez, Javier Mar
Journal: Gut (2014)

A new scenario of therapy for chronic hepatitis C (CHC) is being established with the approval of sofosbuvir (SOF).To estimate the cost-effectiveness of SOF-based regimens approved in the Summary of Product Characteristics (SmPC) versus the standard of care for different genotypes and patient populations (naive or pretreated).A Markov model simulating CHC progression was used to estimate disease treatment costs and effects over patients' lifetimes, from the Spanish National Public Healthcare System perspective. Different therapeutic options were analysed for genotypes 1, 2 and 3 in naive population and for genotype 2 and 3 pretreated patients, according to data obtained from clinical trials. A one-way sensitivity analysis was performed to evaluate the uncertainty of certain parameters: treatment starting age, transition probabilities, drug costs and discount rate. A probabilistic sensitivity analysis was also carried out.For the naive population, the option SOF+pegylated-interferon-α (pIFN)+ribavirin (RBV) for 12 weeks recorded in SmPC for genotype 1 and 3 versus pIFN+RBV for 24 weeks estimated an incremental cost-effectiveness ratio (ICER) below the €40,000/quality-adjusted life-year (QALY) benchmark. For the pretreated population, SOF triple therapy reached an ICER on the threshold limit for genotype 3. Other options included in SmPC for different genotypes exceeded the accepted efficiency limit in our setting.The options that included SOF+RBV+pIFN in a 12-week course regimen fell below the efficiency threshold considered in our setting. IFN-free regimens administered for 24 weeks reached figures over the benchmark of €40,000/QALY.
Measurement of Individual Ventricular Outputs in the Fetal Lamb by a Dye Dilution Technique
Authors: WILLIAM A. MAHON, JAMES W. GOODWIN, WILLIAM M. PAUL
Journal: Circulation Research (1966)

Individual ventricular outputs were measured in 25 fetal lambs using an indicator dilution method. Small volumes of indocyanine green were injected through catheters placed in the individual ventricles; sampling for the left ventricle was from a catheter placed in the brachiocephalic artery through the carotid artery and for the right ventricle sampling was from a catheter placed in the ductus arteriosus via a femoral artery and the aorta. Mean left ventricular output obtained by this method was 181.7 ml/kg per min and mean right ventricular output was 179.7 ml/kg per min. We suggest that the rapidity of preparation and relative lack of trauma involved in this method may account for values that are higher than those reported previously.
Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma.
Authors: I Feoktistov, I Biaggioni
Journal: Journal of Clinical Investigation (1995)

Adenosine potentiates mast cell activation, but the receptor type and molecular mechanisms involved have not been defined. We, therefore, investigated the effects of adenosine on the human mast cell line HMC-1. Both the A2a selective agonist CGS21680 and the A2a/A2b nonselective agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased cAMP, but NECA was fourfold more efficacious and had a Hill coefficient of 0.55, suggesting the presence of both A2a and A2b receptors. NECA 10 microM evoked IL-8 release from HMC-1, but CGS21680 10 microM had no effect. In separate studies we found that enprofylline, an antiasthmatic previously thought to lack adenosine antagonistic properties, is as effective as theophylline as an antagonist of A2b receptors at concentrations achieved clinically. Both theophylline and enprofylline 300 micro completely blocked the release of IL-8 by NECA. NECA, but not CGS21680, increases inositol phosphate formation and intracellular calcium mobilization through a cholera and pertussis toxin-insensitive mechanism. In conclusion, both A2a and A2b receptors are present in HMC-1 cells and are coupled to adenylate cyclase. In addition, A2b receptors are coupled to phospholipase C and evoke IL-8 release. This effect is blocked by theophylline and enprofylline, raising the possibility that this mechanism contributes to their antiasthmatic effects.
THE EFFECT OF PEPTONE ON THE PERIPHERAL CIRCULATION
Authors: J. P. Simonds, S. W. Ranson
Journal: The Journal of Experimental Medicine (1923)

1. Injection of a solution of peptone directly into the artery of the leg of a dog is followed by an abrupt increase in leg volume. This is of short duration and is quickly followed, usually in less than (1/2) minute, by a decrease in the volume of the limb below that previous to the injection. 2. The phases of the leg volume curve bear a fairly definite relation to the changes in arterial pressure. 3. These results, therefore, indicate that the long continued low arterial pressure in peptone shock, and probably in anaphylactic shock, may be hastened but is not maintained by peripheral dilatation, and suggest that there is an impounding of the blood in some other part of the body.
Engineering Artificial Antigen-presenting Cells to Express a Diverse Array of Co-stimulatory Molecules
Authors: Megan M Suhoski, Tatiana N Golovina, Nicole A Aqui, Victoria C Tai, Angel Varela-Rohena, Michael C Milone, Richard G Carroll, James L Riley, Carl H June
Journal: Molecular Therapy (2007)

To facilitate the therapeutic application of antigen-presenting cells (APCs), we have developed a cell-based artificial APC (aAPC) system by engineering K562 cells with lentiviruses to direct the stable expression and secretion of a variety of co-stimulatory molecules and cytokines. Here we report the use of a combinatorial lentiviral gene transfer approach to achieve long-term stable expression of at least seven genes in the K562 parental cell line. Expression of various combinations of genes on the aAPC enables the precise determination of human T-cell activation requirements, such that aAPCs can be tailored for the optimal propagation of T-cell subsets with specific growth requirements and distinct functions. The aAPCs support ex vivo growth and long-term expansion of functional human CD8 T cells without requiring the addition of exogenous cytokines, in contrast to the use of natural APCs. Distinct populations of T cells can be expanded with aAPCs expressing CD137L (4-1BBL) and/or CD80. Finally, the aAPCs provide an efficient platform to expand genetically modified T cells and to maintain CD28 expression on CD8 T cells. Therefore, K562-based aAPCs have therapeutic potential for adoptive immunotherapies and vaccinations.
Epigenetic Inactivation of IκB Kinase-α in Oral Carcinomas and Tumor Progression
Authors: Genta Maeda, Tadashige Chiba, Shuichi Kawashiri, Tazuko Satoh, Kazushi Imai
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The loss of epithelial phenotypes in the process of carcinoma progression correlates with clinical outcome, and genetic/epigenetic changes accumulate aggressive clones toward uncurable disease. IκB kinase-α (IKKα) has a decisive role in the development of the skin and establishes keratinocyte phenotypes. We assessed clinical implications of IKKα expression in oral carcinomas and epigenetic aberrations for the loss of expression. Experimental Design: We examined IKKα expression in oral carcinomas by immunostaining (n = 64) and genetic instability by microsatellite PCR (n = 46). Promoter methylation status was analyzed by bisulfite-modified sequence (n = 11). Results: IKKα was expressed in the nucleus of basal cells of normal oral epithelium, but not or marginally detected in 32.8% of carcinomas. The immunoreactivity was significantly decreased in less differentiated carcinomas (P &amp;lt; 0.05) and correlated to long-term survival of patients (P &amp;lt; 0.01) with an independent prognostic value (P &amp;lt; 0.05). Although allelic/biallelic loss of the gene was limited to four cases, we detected microsatellite instability in 63.0% cases in which the immunoreactivities were decreased and the promoter was hypermethylated. Conclusion: These results showed that oral carcinomas exhibiting genetic instability and promoter hypermethylation down-regulate expression of IKK and suggest that the epigenetic loss of the expression closely associates with disease progression toward unfavorable prognosis.
Gender Differences in the Risk of Ischemic Stroke and Peripheral Embolism in Atrial Fibrillation
Authors: Margaret C. Fang, Daniel E. Singer, Yuchiao Chang, Elaine M. Hylek, Lori E. Henault, Nancy G. Jensvold, Alan S. Go
Journal: Circulation (2005)

Background— Previous studies provide conflicting results about whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation (AF). We examined data from a large contemporary cohort of AF patients to address this question. Methods and Results— We prospectively studied 13 559 adults with AF and recorded data on patients’ clinical characteristics and the occurrence of incident hospitalizations for ischemic stroke, peripheral embolism, and major hemorrhagic events through searching validated computerized databases and medical record review. We compared event rates by patient sex using multivariable log-linear regression, adjusting for clinical risk factors for stroke, and stratifying by warfarin use. We identified 394 ischemic stroke and peripheral embolic events during 15 494 person-years of follow-up off warfarin. After multivariable analysis, women had higher annual rates of thromboembolism off warfarin than did men (3.5% versus 1.8%; adjusted rate ratio [RR], 1.6; 95% CI, 1.3 to 1.9). There was no significant difference by sex in 30-day mortality after thromboembolism (23% for both). Warfarin use was associated with significantly lower adjusted thromboembolism rates for both women and men (RR, 0.4; 95% CI, 0.3 to 0.5; and RR, 0.6; 95% CI, 0.5 to 0.8, respectively), with similar annual rates of major hemorrhage (1.0% and 1.1%, respectively). Conclusions— Women are at higher risk than men for AF-related thromboembolism off warfarin. Warfarin therapy appears be as effective in women, if not more so, than in men, with similar rates of major hemorrhage. Female sex is an independent risk factor for thromboembolism and should influence the decision to use anticoagulant therapy in persons with AF.
Effects of intense antecedent sympathetic stimulation on sympathetic neurotransmission in the heart.
Authors: T Yang, M N Levy
Journal: Circulation Research (1993)

We studied the effects of intense sympathetic stimulation on the chronotropic responses of the heart to subsequent test stimulations of the cardiac autonomic nerves in dogs anesthetized with alpha-chloralose. Such intense sympathetic stimulations (which we refer to as "release stimulations") are known to release neuropeptide Y as well as norepinephrine. The changes in cardiac cycle length evoked by vagal and sympathetic test stimulations were progressively more attenuated as we increased the frequency and duration of the antecedent sympathetic release stimulations. We found that 2.5 minutes after a maximal release stimulation (30 Hz for 5 minutes), the mean +/- SEM chronotropic responses to the vagal and sympathetic test stimulations were diminished to 36.5 +/- 1.6% and 54.7 +/- 1.3% respectively, of the prestimulation responses. The mean times for the chronotropic responses to the vagal and sympathetic test stimulations to recover to their control values were 52.0 +/- 1.3 and 63.2 +/- 2.9 minutes, respectively. This enduring effect suggests the action of a neuropeptide, such as neuropeptide Y. Phentolamine potentiated the inhibitory effects of the sympathetic release stimulations. The chronotropic responses to isoproterenol infusions were not affected appreciably by antecedent sympathetic release stimulation. We conclude, therefore, that the inhibitory effects of antecedent sympathetic release stimulation on cardiac sympathetic neurotransmission are mediated prejunctionally, probably via an inhibition of the neuronal release of norepinephrine by neuropeptide Y.
KIT (CD117)-Positive Breast Cancers Are Infrequent and Lack KIT Gene Mutations
Authors: Ronald Simon, Soti Panussis, Robert Maurer, Hanspeter Spichtin, Kathrin Glatz, Coya Tapia, Martina Mirlacher, Alex Rufle, Joachim Torhorst, Guido Sauter
Journal: Clinical Cancer Research (2004)

Abstract Purpose: KIT (CD117) is a transmembrane tyrosine kinase representing a target for STI571 (Glivec) therapy. Some KIT-overexpressing solid tumors have responded favorably to STI571, potentially because of the presence of KIT-activating mutations. Experimental Design: To investigate the epidemiology of KIT overexpression and mutations, we investigated a series of 1654 breast cancers. All tumors were analyzed by immunohistochemistry in a tissue microarray format. Results: KIT expression was always present in normal breast epithelium. However, cancer analysis revealed the only 43 of 1654 (2.6%) tumors were KIT-positive. KIT expression was more frequent in medullary cancer (9 of 47 positive; 19.1%) than in any other histological tumor subtype (P &amp;lt; 0.001). KIT expression was significantly associated with high tumor grade (P &amp;lt; 0.0001) but unrelated to pT and pN categories or patient survival. Mutation analysis of exons 2, 8, 9, 11, 13, and 17 was negative in 10 KIT-positive tumors. Conclusions: Overall, our data show that a high level of KIT expression occurs infrequently in breast cancer. KIT-positive breast cancers may not reflect “KIT up-regulation” because KIT is also expressed in normal breast epithelium. The lack of KIT mutations also argues against the therapeutic efficacy of STI571 in breast cancer.
Cyclooxygenase 2 Promotes Parathyroid Hyperplasia in ESRD
Authors: Qian Zhang, Junsi Qiu, Haiming Li, Yanwen Lu, Xiaoyun Wang, Junwei Yang, Shaoqing Wang, Liyin Zhang, Yong Gu, Chuan-Ming Hao, Jing Chen
Journal: Journal of the American Society of Nephrology (2011)

Hyperplasia of the PTG underlies the secondary hyperparathyroidism (SHPT) observed in CKD, but the mechanism underlying this hyperplasia is incompletely understood. Because aberrant cyclooxygenase 2 (COX2) expression promotes epithelial cell proliferation, we examined the effects of COX2 on the parathyroid gland in uremia. In patients with ESRD who underwent parathyroidectomy, clusters of cells within the parathyroid glands had increased COX2 expression. Some COX2-positive cells exhibited two nuclei, consistent with proliferation. Furthermore, nearly 78% of COX2-positive cells expressed proliferating cell nuclear antigen (PCNA). In the 5/6-nephrectomy rat model, rats fed a high-phosphate diet had significantly higher serum PTH levels and larger parathyroid glands than sham-operated rats. Compared with controls, the parathyroid glands of uremic rats exhibited more PCNA-positive cells and greater COX2 expression in the chief cells. Treatment with COX2 inhibitor celecoxib significantly reduced PCNA expression, attenuated serum PTH levels, and reduced the size of the glands. In conclusion, COX2 promotes the pathogenesis of hyperparathyroidism in ESRD, suggesting that inhibiting the COX2 pathway could be a potential therapeutic target.
Do Nursing Interventions Targeting Concurrent Symptoms Hold Promise for Managing Fatigue in Patients With Advanced Cancer?
Authors: Raymond J. Chan
Journal: Journal of Clinical Oncology (2013)

TO THE EDITOR: 

It was with great interest that I read two recent articles by de Raaf et al1, and Bruera et al2. These authors are to be congratulated for completing two of the very few high quality randomized trials that evaluate complex interventions for managing fatigue in patients with advanced cancer. de Raaf et al conducted a non-blinded RCT with 152 patients with advanced cancer and reported significant reduction of fatigue in patients who received a nurse-led monitoring and protocol-guided treatment of physical symptoms compared with those who received usual care1. Patients who received this intervention experienced a significant improvement over time in general fatigue, at one-month follow-up and two-month follow-up. Another recent RCT conducted with 141 patients with advanced cancer by Bruera et al2 did not find any benefits of a nursing telephone intervention that involved systematic symptom assessment/management, medication review, psychosocial support and patient education in fatigue reduction, compared to those who received a control telephone intervention conducted by a non-professional...
H. Influenzae Meningitis
Authors: H. W. E. Jones
Journal: BMJ (1937)

In view of the recent interest shown in this condition it seems fitting to record the following six cases which have been treated in St. Thomas's Hospital during the last fifteen years.The records of all departments of the hospital have been reviewed, but the only cases found were those in children, no adult cases being recorded.Case 1 E. H., a female, aged 1 year 3 months, and a two months premature baby, had had bronchopneumonia at 10 months She was admitted on July 23, 1922, with one day's history of malaise, restlessness, and "stiffness."She had vomited once.State.-Temperature 103.3°, pulse 144, respirations 35.Drowsy, but irritable when roused.The anterior fontanelle was tense.There was a moderate degree of neck rigidity and occasional convulsive movements of the right hand.No other physical signs were present, and the lungs were clear.The cerebrospinal fluid was turbid and under raised pressure.A very large number of cells were present, nearly all polymorphs.H. infliuenzae was seen in a direct smear and on culture.Blood culture showed H. inifluenzae.Progress.-Thepatient ran a high remittent temperature, and in spite of daily lumbar punctures died on August 8, after an illness of thirteen days.Necropsy.-Thevertex and base of the brain were covered with plaques of thick yellow exudate.There was some degree of internal hydrocephalus, and the brain was congested.The upper lobe of the right lung was collapsed, but there was no sign of pneumonia.The liver was large, pale, and fatty.Smears and cultures of the pus showed H. influenzae.Case 2 J. S., male, aged 11 months, was admitted on January 7, 1925, with several days' history of vague lassitude and irritability.Temperature, pulse, and respirations were normal, and menin- gitis was not suspected until January 20, when he had, in addition to the above, definite neck rigidity and his temperature began to rise (101°).A lumbar puncture revealed a cerebrospinal fluid which was under raised pressure and was slightly turbid.Microscopy showed pus cells + +, and no organisms were seen in a direct smear.On culture H. inifluenzae was shown to be the causative organism.His blood serum agglutinated H. influenzae in a titre of 1 in 100.He was lumbar-punctured six times during the next nine days, but became comatose and died on January 29, his temperature rising to 106°b efore death.The duration of the disease was about twenty-five days.Necropsy.-There was a thick yellow exudate on the base of the brain and some purulent patches over the vertex.H. influenzae was demonstrated in the exudate.The ofher organs were normal except for a pale fatty liver.Case 3 M. S., a female, aged 8 months, a perfectly normal child, fell off a chair on to her head on March 21, 1930.On being picked up she vomited immediately, and continued to do so nearly every half-hour.She was admitted to hospital on March 22.
Mesothelioma incidence projections in South East England
Authors: Sharma P. Riaz, Victoria H. Coupland, Margreet Lüchtenborg, Michael D. Peake, Henrik Møller
Journal: European Respiratory Journal (2012)

We estimated the past and future age-standardised incidence rates of mesothelioma by birth cohort and by period of diagnosis in South East England. We extracted data on patients diagnosed with mesothelioma (International Classification of Diseases-10 C45) between 1960 and 2009 from the Thames Cancer Registry. We calculated the age-standardised incidence rates using the European standard population. We used age-cohort and age-period modelling to estimate the age-specific incidence rates for the 1900 to 1950 birth cohorts and the 1935 to 2034 calendar periods. A much more pronounced increase in mesothelioma incidence between 1972 and 2007 was observed in males than in females. In both sexes, the incidence rates increased in successive generations up to the 1945 birth cohort. Projection of rates in the future showed an increase in incidence in males until 2022 and a decrease thereafter. Among females, the incidence rate was predicted to increase gradually until reaching its maximum around 2027, and to remain stable thereafter. The occurrence of mesothelioma is closely linked to occupational exposure to asbestos in the 1960s and 1970s and, due to the long latency period, the incidence of mesothelioma is projected to increase until the 2020s.