tbuckley/cabot-search huggingface dataset:
Cardioselective β-Blockers in Patients with Reactive Airway Disease
Authors: Shelley R. Salpeter, Thomas M. Ormiston, Edwin E. Salpeter
Journal: Annals of Internal Medicine (2002)

Objective: To assess the effect of cardioselective β-blockers on respiratory function of patients with reactive airway disease. Data Sources: Comprehensive searches of the EMBASE, MEDLINE, and CINAHL databases from 1966 to May 2001 and scanning of references of the identified articles and related reviews. Study Selection: Randomized, blinded, placebo-controlled trials that studied the effects of cardioselective β-blockers on FEV1, symptoms, and the use of inhaled β2-agonists in patients with reactive airway disease were selected. Interventions studied were the administration of a cardioselective β-blocker and administration of β2-agonist after the study drug. Data Extraction: Outcomes measured were the change in FEV1 from baseline, the number of patients with respiratory symptoms, and the use of inhaled β2-agonists with active treatment compared with placebo. Data Synthesis: Nineteen studies on single-dose treatment and 10 studies on continued treatment were included. Administration of a single dose of a cardioselective β-blocker was associated with a 7.46% (95% CI, 5.59% to 9.32%) decrease in FEV1 and a 4.63% (CI, 2.47% to 6.78%) increase in FEV1 response to β-agonist compared with placebo, with no increase in symptoms. Trials lasting from 3 days to 4 weeks produced no significant change in FEV1 (−0.42% [CI, −3.74% to 2.91%]), symptoms, or inhaler use compared with placebo but maintained an 8.74% (CI, 1.96% to 15.52%) increase in β-agonist response. No significant treatment effect in terms of FEV1 was found in patients with concomitant chronic obstructive pulmonary disease, whether single doses (change in FEV1, −5.28% [CI, −10.03% to −0.54%]) or continued treatment (change in FEV1, 1.07% [CI, −3.3% to 5.44%]) was given. Conclusions: Cardioselective β-blockers do not produce clinically significant adverse respiratory effects in patients with mild to moderate reactive airway disease. The results were similar for patients with concomitant chronic airways obstruction. Given their demonstrated benefit in such conditions as heart failure, cardiac arrhythmias, and hypertension, cardioselective β-blockers should not be withheld from patients with mild to moderate reactive airway disease.
Perfecting peptide priming
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

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Slight alterations in peptide sequence alter the peptide–HLA–TCR interaction and affect T cell priming.A single amino acid change in a tumor-derived peptide results in the priming of a bigger and better T cell response upon vaccination, according to a study by Chen
A Polymer–(Tandem Drugs) Conjugate for Enhanced Cancer Treatment
Authors: Dongfang Zhou, Haihua Xiao, Fanbo Meng, Xiaoyuan Li, Yuxin Li, Xiabin Jing, Yubin Huang
Journal: Advanced Healthcare Materials (2013)

A novel strategy for combination chemotherapy (platinum and demethylcantharidin) via a polymer-(tandem drugs) conjugate for enhanced cancer treatment is demonstrated. Cisplatin can be released inside cell by reduction to attack DNA, while DMC will be hydrolyzed subsequently to block DNA-damage-induced defense mechanisms by serine/threonine phosphatase PP2A inhibition. Synergistic effect of the polymer-(tandem drugs) conjugate causes complete suppression of H22 liver tumor xenografts without recurrence.
Polyethylene glycol 4000 as a continuously administered non-absorbable faecal marker for metabolic balance studies in human subjects
Authors: R. Wilkinson
Journal: Gut (1971)

The use of polyethylene glycol 4000 as a non-absorbable, continuously fed faecal marker is described. The intestinal handling and transit of polyethylene glycol is compared with that of chromium sesquioxide and barium sulphate. Polyethylene glycol is an acceptable non-absorbable faecal marker for calcium, phosphorus, and fatty acids, and has several features which commend its use in preference to insoluble chromium sesquioxide and barium sulphate particularly when marking water-soluble dietary constituents.
PRIMARY HEMANGIOSARCOMA OF THE SPLEEN DIAGNOSED BY NEEDLE BIOPSY
Authors: M. Wachstein
Journal: JAMA (1953)

Splenic aspiration, apparently used first in France for the cultural demonstration of typhoid bacilli more than 50 years ago, has been employed in the diagnosis of various hematological disorders by many European investigators. 1a Only recently has its use been advocated in this country by Block and Jacobson 2 and by Morrison and his co-workers. 3a It is the purpose of this report to present an instance in which splenic biopsy was the only means of diagnosing a primary splenic tumor. To our knowledge, this is the first case reported in the literature in which the diagnosis of hemangiosarcoma originating in the spleen was established prior to the removal of the organ on the operating table or at autopsy. Several cases, however, have been reported in which lymphosarcoma and reticulum cell sarcoma of the spleen were diagnosed by splenic aspiration. 1   REPORT OF A CASE  The patient was a 62-year-old
Body Mass Index and Risk of Incident Hypertension Over the Life Course
Authors: Hasan M. Shihab, Lucy A. Meoni, Audrey Y. Chu, Nae-Yuh Wang, Daniel E. Ford, Kung-Yee Liang, Joseph J. Gallo, Michael J. Klag
Journal: Circulation (2012)

Background— The obesity-hypertension link over the life course has not been well characterized, although the prevalence of obesity and hypertension is increasing in the United States. Methods and Results— We studied the association of body mass index (BMI) in young adulthood, into middle age, and through late life with risk of developing hypertension in 1132 white men of The Johns Hopkins Precursors Study, a prospective cohort study. Over a median follow-up period of 46 years, 508 men developed hypertension. Obesity (BMI ≥30 kg/m 2 ) in young adulthood was strongly associated with incident hypertension (hazard ratio, 4.17; 95% confidence interval, 2.34–7.42). Overweight (BMI 25 to &lt;30 kg/m 2 ) also signaled increased risk (hazard ratio, 1.58; 95% confidence interval, 1.28–1.96). Men of normal weight at age 25 years who became overweight or obese at age 45 years were at increased risk compared with men of normal weight at both times (hazard ratio, 1.57; 95% confidence interval, 1.20–2.07), but not men who were overweight or obese at age 25 years who returned to normal weight at age 45 years (hazard ratio, 0.91; 95% confidence interval, 0.43–1.92). After adjustment for time-dependent number of cigarettes smoked, cups of coffee taken, alcohol intake, physical activity, parental premature hypertension, and baseline BMI, the rate of change in BMI over the life course increased the risk of incident hypertension in a dose-response fashion, with the highest risk among men with the greatest increase in BMI (hazard ratio, 2.52; 95% confidence interval, 1.82–3.49). Conclusions— Our findings underscore the importance of higher weight and weight gain in increasing the risk of hypertension from young adulthood through middle age and into late life.
Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Authors: J. Oldenburg, S.D. Fosså, J. Nuver, A. Heidenreich, H.-J. Schmoll, C. Bokemeyer, A. Horwich, J. Beyer, V. Kataja
Journal: Annals of Oncology (2013)
The natural history of histologically proved drug induced liver disease
Authors: P G Aithal, C P Day
Journal: Gut (1999)

The long term outcome of drug related liver disease is unknown.To study the natural history of histologically proved drug induced hepatotoxicity.110 patients with liver biopsies coded either as drug induced liver disease or hepatitis/cholestasis of unknown aetiology were identified from hospital records 1978-1996. Review of case notes and histology identified 44 patients with definite drug induced hepatotoxicity. Forty surviving patients were invited to attend a follow up clinic. History, examination, full liver screen, and isotope and ultrasound liver scans were repeated in all patients. Repeat liver biopsies were offered to patients with abnormal liver tests.Presentation at index biopsy was jaundice in 24 patients, abnormal liver tests in 17, and hepatic failure in three. Antibiotics (n=13) and non-steroidal anti-inflammatory drugs (n=11) were the most common drugs implicated. Initial histology showed acute hepatitis in six, chronic hepatitis in 20, and cholestasis in 18. At 1-19 years (median 5 years) follow up, 13/33 (39%) patients had persistent significant abnormalities in their liver blood tests and/or scans. Three of the five repeat liver biopsies performed showed significant abnormalities. Factors predicting persistence or development of chronic liver disease were fibrosis and continued exposure to the drug.Drugs should be considered in the differential diagnosis of abnormal liver function and/or histology, as failure to withdraw the offending drug is associated with a high risk of persistent liver damage.
Randomized phase II trial of gemcitabine plus irinotecan or docetaxel in stage IIIB or stage IV NSCLC
Authors: C.M. Rocha Lima, N.A. Rizvi, C. Zhang, J.E. Herndon, J. Crawford, R. Govindan, G.W. King, M.R. Green
Journal: Annals of Oncology (2004)
Adaptive Evolution as a Predictor of Species-Specific Innate Immune Response
Authors: Andrew E. Webb, Z. Nevin Gerek, Claire C. Morgan, Thomas A. Walsh, Christine E. Loscher, Scott V. Edwards, Mary J. O’Connell
Journal: Molecular Biology and Evolution (2015)

It has been proposed that positive selection may be associated with protein functional change. For example, human and macaque have different outcomes to HIV infection and it has been shown that residues under positive selection in the macaque TRIM5α receptor locate to the region known to influence species-specific response to HIV. In general, however, the relationship between sequence and function has proven difficult to fully elucidate, and it is the role of large-scale studies to help bridge this gap in our understanding by revealing major patterns in the data that correlate genotype with function or phenotype. In this study, we investigate the level of species-specific positive selection in innate immune genes from human and mouse. In total, we analyzed 456 innate immune genes using codon-based models of evolution, comparing human, mouse, and 19 other vertebrate species to identify putative species-specific positive selection. Then we used population genomic data from the recently completed Neanderthal genome project, the 1000 human genomes project, and the 17 laboratory mouse genomes project to determine whether the residues that were putatively positively selected are fixed or variable in these populations. We find evidence of species-specific positive selection on both the human and the mouse branches and we show that the classes of genes under positive selection cluster by function and by interaction. Data from this study provide us with targets to test the relationship between positive selection and protein function and ultimately to test the relationship between positive selection and discordant phenotypes.
Identifying disease mutations in genomic medicine settings: current challenges and how to accelerate progress
Authors: Gholson J Lyon, Kai Wang
Journal: Genome Medicine (2012)

The pace of exome and genome sequencing is accelerating, with the identification of many new disease-causing mutations in research settings, and it is likely that whole exome or genome sequencing could have a major impact in the clinical arena in the relatively near future. However, the human genomics community is currently facing several challenges, including phenotyping, sample collection, sequencing strategies, bioinformatics analysis, biological validation of variant function, clinical interpretation and validity of variant data, and delivery of genomic information to various constituents. Here we review these challenges and summarize the bottlenecks for the clinical application of exome and genome sequencing, and we discuss ways for moving the field forward. In particular, we urge the need for clinical-grade sample collection, high-quality sequencing data acquisition, digitalized phenotyping, rigorous generation of variant calls, and comprehensive functional annotation of variants. Additionally, we suggest that a 'networking of science' model that encourages much more collaboration and online sharing of medical history, genomic data and biological knowledge, including among research participants and consumers/patients, will help establish causation and penetrance for disease causal variants and genes. As we enter this new era of genomic medicine, we envision that consumer-driven and consumer-oriented efforts will take center stage, thus allowing insights from the human genome project to translate directly back into individualized medicine.
THE CONCENTRATIONS OF CYSTEINE AND CYSTINE IN HUMAN BLOOD PLASMA
Authors: M. Prince Brigham, William H. Stein, Stanford Moore
Journal: Journal of Clinical Investigation (1960)

Studies on the amino acid content of physiological fluids have usually been carried out under conditions that would permit any cysteine present to be oxidized to cystine prior to analysis. Consequently, little quantitative information has been obtained concerning the relative amounts of the -SH and the -S-S- forms of the amino acid in plasma. To know whether both forms are present is of particular importance in the study of excretion of amino acids by the kidney. Cystine is an amino acid which appears in abnormal quantities in the urine in several pathological conditions (1). Failure of tubular reabsorption has usually been invoked to explain this fact (2), an explanation which tacitly assumes that it is cystine (the -S-S- form) not cysteine (the -SH form) that is circulating in the blood and is cleared by the kidney. If cysteine were to be the predominant form normally circulating, oxidation to cystine in the kidney would be required in order to account for the excretion of the disulfide in the urine. Fujita and Numata (3) and Smith and Tuller (4) have reported the presence of cysteine in blood. Another observation which could bear on the subject is that of Brand, Cahill and Harris (5) who showed that the amount of cystine in the urine of a cystinuric subject rose after feeding cysteine and methionine, but not after the ingestion of cystine, the sulfur of which appeared almost exclusively as urinary sulfate. With these thoughts in view, a method has been
Neutral endopeptidase inhibition with inhaled phosphoramidon: no effect on bronchial responsiveness to adenosine 5'-monophosphate (AMP) in asthma
Authors: R Polosa, G Santonocito, S Magri, G Paolino, F Armato, C Pagano, N Crimi
Journal: European Respiratory Journal (1997)

Part of the contractile response of adenosine in the asthmatic airways may be due to the activation of peptidergic pathways with subsequent local release of spasmogenic neuropeptides. At present, little is known about the potential role of lung peptidases in modulating adenosine-induced airway dysfunction in humans in vivo. We have, therefore, investigated the change in bronchial reactivity to adenosine 5'-monophosphate (AMP), after treatment with inhaled phosphoramidon, a potent neutral endopeptidase (NEP) inhibitor, in a double-blind, placebo-controlled, randomized study of 12 asthmatic subjects. Subjects attended on six separate occasions, during which concentration response studies with inhaled AMP and methacholine were carried out, initially in the absence of treatment and then after nebulized phosphoramidon sodium salt (10[-5] M) or matched placebo 5 min prior to a bronchoprovocation test with AMP or methacholine. Agonist responsiveness was expressed as the provocative concentration of AMP or methacholine producing a 20% fall in FEV1 from baseline (PC[20,AMP] or PC[20,meth], respectively). When compared to placebo, phosphoramidon failed to potentiate the airway response to AMP. The geometric mean (range) PC20 AMP value of 23.4 (4.4-190.6) mg x mL(-1) after placebo was not significantly different from that of 20.7 (45-100.9) mg x mL(-1) obtained after phosphoramidon. The lack of change in bronchial reactivity to adenosine 5'-monophosphate after phosphoramidon indicates that endogenous airway neutral endopeptidase may not be of physiological importance in modulating the contractile response of adenosine in the airways. Thus, the present data do not support the view that activation of peptidergic pathways with subsequent local release of spasmogenic neuropeptides is important in the airway response to adenosine
Experts to scrutinise quality of clinical managers needed for new NHS
Authors: A. O'Dowd
Journal: BMJ (2010)

Health policy experts are launching a wide ranging inquiry into the quality of clinical managers and leaders now and for the future NHS.

The think tank the King’s Fund is launching a commission to assess the leadership and management needs of the NHS.

The decision to study this area was prompted by the announcement of the radical reforms planned for the NHS under the government’s white paper Equity and Excellence—Liberating the NHS , which the King’s Fund say are the biggest changes to the health service since it was set …
Locally invasive hepatic angiosarcoma: an unusual cause of massive haemothorax.
Authors: Y T Wang, S C Wong, A Thomas
Journal: Thorax (1983)

Between July 1968 and December 1976, 9364 consecutive patients with coronary insufficiency underwent direct myocardial revascularisation using aortocoronary bypass (ACB). Among these patients 8017 had ACB alone, and the remaining 1347 had ACB in addition to correction of other cardiac and vascular lesions. In the series of patients having ACB alone the hospital (early) mortality was 3.9%, but for 2383 surgical patients in 1976 this figure was 2.2%. Operative mortality was higher for women (6.85%) than for men (3.5%), but late survival was about the same for both sexes. Among surviving patients 88% were improved or symptom-free after undergoing ACB. According to our data, at the end of eight years 80% of the patients will be survivors. These results, when compared with other series of patients treated medically, indicate the superiority of surgical treatment both in terms of symptomatic relief and also in increased life expectancy.
An analysis of the effects of acetylcholine on conduction and refractoriness in the rabbit sinus node.
Authors: E N Prystowsky, A O Grant, A G Wallace, H C Strauss
Journal: Circulation Research (1979)

The effects of acetylcholine (ACh) on sinus node automaticity, atrio-sinus conduction, and refractoriness were studied in 41 isolated rabbit right atrial preparations. Average control rate was 126 beats/min, and ACh 5 x 10(-8) M, 5 x 10(-7) M, and 5 x 10(-6) M significantly decreased heart rate by 7, 15, and 43%, respectively (P less than 0.01, 0.001, and 0.001). Atrio-sinus conduction time at a pacing cycle length of 400 msec did not significantly change during exposure to ACh 5 x 10(-8) and 5 x 10(-7) M. However, the mean effective refractory period (ERP) of the sinus node, at a pacing cycle length of 400 msec, increased from 183 +/- 16 msec to 210 +/- 24 msec during exposure to ACh 5 x 10(-7) M (P less than 0.025). The change in ERP followed the change in action potential duration. In contrast to the lack of effect of ACh 5 x 10(-7) M on atrio-sinus conduction time, ACh 5 x 10(-6) M caused 2:1 atrio-sinus block in 8 of 10 experiments. The site of block was identified using multiple microelectrode impalements, and occurred between the perinodal fibers bordering on the edge of the sinus node and the pacemaker area in the sinus node proper. When the pacing cycle length was increased and 1:1 atrio-sinus conduciton was present, conduction time did not significantly differ from control. At this longer pacing cycle length the mean ERP of the sinus node was 380 msec greater than control and lasted well after repolarization was completed. Thus, atrio-sinus block during exposure to ACh 5 x 10(-6) M resulted from a marked prolongation of refractoriness.
Immunity to Growth Factor Receptor–Bound Protein 10, a Signal Transduction Molecule, Inhibits the Growth of Breast Cancer in Mice
Authors: InSug O-Sullivan, Amla Chopra, Janai Carr, Tae Sung Kim, Edward P. Cohen
Journal: Cancer Research (2008)

Abstract This study describes the application of a unique strategy to identify breast cancer antigens [tumor-associated antigen (TAA)]. In a mouse model, the strategy led to the identification of growth factor receptor–bound protein 10 (Grb10) as a newly identified TAA. Grb10 is a signal transduction molecule associated with multiple transmembrane tyrosine kinase receptors. It was discovered by comparing microarrays of cellular breast cancer vaccines highly enriched for cells that induced breast cancer immunity in tumor-bearing mice with nonenriched vaccines. The vaccines were prepared by transferring a cDNA expression library derived from SB5b cells, a breast cancer cell line C3H/He origin (H-2k), into LM mouse fibroblasts (H-2k). As the transferred cDNA integrates spontaneously into the genome of the recipient cells, replicates as the cells divide, and is expressed, the vaccine could be prepared from microgram amounts of tumor tissue. Relatively few cells in the transduced cell population, however, incorporated cDNA fragments that included genes specifying TAA. (The vast majority specified normal cellular constituents.) A unique strategy was used, therefore, to enrich the vaccine for immunotherapeutic cells. Twenty genes were overrepresented in the enriched vaccines. One, the gene for Grb10, was ∼100-fold overrepresented. To determine if Grb10 in the enriched vaccine was partly responsible for its therapeutic benefits, the gene was transferred into the fibroblast cell line, which was then used as a vaccine. Mice with established breast cancer treated solely by immunization with the modified fibroblasts developed robust immunity to the breast cancer cells, which, in some instances, was sufficient to result in tumor rejection. [Cancer Res 2008;68(7):2463–70]
Community-acquired pneumonia as an emergency: time for an aggressive intervention to lower mortality
Authors: S Ewig, A Torres
Journal: European Respiratory Journal (2011)

Community-acquired pneumonia (CAP) is one of the major contemporary acute life-threatening conditions. Short-term mortality reaches 14% (7% if nursing-home residents and bedridden patients are excluded) and long-term mortality reaches 50% within 5 yrs. CAP and acute myocardial infarction (AMI) have a lot in common with regard to acuity, prognosis, need for risk stratification and early intervention, and secondary prevention measures. The obvious success in the treatment of AMI is due to an effective organisation of pre-hospital care and evidence-based interventions in the hospital within defined timescales. Less evidence is available about effective strategies to lower short- and long-term mortality in patients with CAP. Nevertheless, it is estimated that ∼ 30% of hospitalised patients with CAP could be subject to a management approach in parallel to that of acute coronary syndrome (ACS). Management of patients with severe CAP should be intensified using all elements that have been established in the care for patients with ACS and stroke. One of the main challenges of future research will be to define whether and which additional patients at risk of mortality truly profit from timely and structured interventions. In the meantime, patients at increased risk of death according to clinical prediction tools should also be subject to an aggressive management approach.