tbuckley/cabot-search huggingface dataset:
Standardisation of gas mixtures for estimating carbon monoxide transfer factor.
Authors: A H Kendrick, G Laszlo
Journal: Thorax (1993)

The American Thoracic Society recommends that the inspired concentration used for the estimation of carbon monoxide transfer factor (TLCO) mixture should be 0.25-0.35% carbon monoxide, 10-14% helium, 17-21% oxygen, balance nitrogen. Inspired oxygen influences alveolar oxygen and hence carbon monoxide uptake, such that transfer factor increases by 0.35% per mm Hg decrease in alveolar oxygen. To aid in the standardisation of TLCO either a known inspired oxygen concentration should be used, or TLCO should be corrected to a standard inspired oxygen concentration. The range of gas mixtures used in practice and the implications for cost and accuracy have been investigated.A questionnaire was sent to 185 respiratory units in the UK requesting information on (1) the method used to estimate TLCO, (2) the manufacturer of the equipment, (3) the mixture used, (4) whether "medical quality" gas was ordered, and (5) the level of satisfaction with supplier service.Replies were received from 106 units. Most used the single breath breath holding method for which 17 different test mixtures were ordered. One unit also used the single breath exhalation method. Inspired oxygen ranged from 17.94% to 25%, giving a wide variation in alveolar oxygen and hence TLCO. Forty seven units ordered a specific inspired oxygen, the rest ordering "air" as balance. The cost per litre of gas varied greatly, with the mixture 14% helium, 0.28% carbon monoxide, balance air (17.9% oxygen) and 10% helium, 0.28% carbon monoxide, balance air (18.8% oxygen) being cheapest to produce. Ordering a specific inspired oxygen concentration increased the cost. Large cylinders of gas were cheaper for the same mixture. The mixture for the exhalation method was the most expensive. Sixty seven units ordered "medical quality" gas and six assumed this was supplied. Twenty nine (27%) were dissatisfied with their supplier due to (1) poor service, (2) long delivery times, (3) costs, or (4) wrongly labelled cylinders.It is recommended that two mixtures be available: (a) 14% helium, 0.28% carbon monoxide, balance air for a helium analyser reading up to 15%, and (b) 10% helium, 0.28% carbon monoxide, balance air for lower reading helium analysers. The mixture should be produced under a medical product licence. The advantage of the single exhalation method for routine clinical use needs to be investigated in view of the higher cost of the mixture.
Abstract 2021: Characterization of myeloma tumors from a multi-ethnic cohort using cytogenetics and genomic analysis.
Authors: Angela S. Baker, Esteban Braggio, Susana Jacobus, Sungwon Jung, Dirk Larson, Terry Therneau, Angela Dispenzieri, Scott A. Van Wier, Gregory Ahmann, Joan Levy, Louise Perkins, Seungchan Kim, Kim Henderson, David Vesole, S. Vincent Rajkumar, Dianne F. Jelinek, John Carpten, Rafael Fonseca
Journal: Cancer Research (2013)

Abstract The plasma cell malignancy Multiple Myeloma (MM) is a rare but deadly form of cancer with 5 year survival rates of ∼30%. Epidemiological studies have suggested that MM exacts an especially heavy burden on African American (AA) patients. We examined a multi-ethnic cohort of MM tumors to assess potential differences in the frequency of molecular events in tumors derived from either African American (AA) or European American (EA) patients. The frequency of 14q32 translocation breakpoints at the IgH locus was compared among a series of data from 115 AA MM patients from three studies and EA MM from the Eastern Cooperative Oncology Group (ECOG). In addition, we analyzed matching genome-wide copy number and transcriptional data among 45 AA MM tumors and 196 EA MM tumors to determine differences in the frequency of molecular events in tumors from these populations. No differences were found for specific translocation subtypes; however, we detected a statistically significant difference in the overall frequency of IgH translocations between the two groups, which occurred more frequently in EA patients (52% vs. 40%; p = 0.032). When assessing genomic copy number events previously shown to be associated with poor outcome in MM, frequencies of alterations were not significant after correcting for multiple testing. Furthermore, there was not a significant difference in the association of high-risk disease using expression profiling. Our study represents the first comprehensive assessment of the frequency and distribution of molecular alterations in MM tumors from both AA and EA patients and could help shed light on possible biological features associated with population differences in incidence and outcome in MM. Citation Format: Angela S. Baker, Esteban Braggio, Susana Jacobus, Sungwon Jung, Dirk Larson, Terry Therneau, Angela Dispenzieri, Scott A. Van Wier, Gregory Ahmann, Joan Levy, Louise Perkins, Seungchan Kim, Kim Henderson, David Vesole, S. Vincent Rajkumar, Dianne F. Jelinek, John Carpten, Rafael Fonseca. Characterization of myeloma tumors from a multi-ethnic cohort using cytogenetics and genomic analysis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2021. doi:10.1158/1538-7445.AM2013-2021
Novel relationship of serum cholesterol with asthma and wheeze in the United States
Authors: Michael B. Fessler, Mark W. Massing, Brian Spruell, Renee Jaramillo, David W. Draper, Jennifer H. Madenspacher, Samuel J. Arbes, Agustin Calatroni, Darryl C. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2009)
Phase 2 study of dual VEGF/HER2 blockade with pazopanib + lapatinib in patients with first-line HER2 positive advanced or metastatic (adv/met) breast cancer.
Authors: DJ Slamon, SM Stemmer, S Johnston, S Kim, M Durante, LN Pandite, DF Roychowdhury, VL Goodman
Journal: Cancer Research (2009)

Abstract Abstract #4114 Background: Evidence indicates a direct molecular link between HER2 amplification and up-regulation of VEGF in HER2+ breast cancer. Concurrent over-expression of HER2 and VEGF is associated with a poorer clinical outcome than over-expression of either alone. These data provide the rationale for simultaneous blockade of both pathways. Pazopanib (P) is an oral angiogenesis inhibitor targeting VEGFR, PDGFR, and c-kit. Lapatinib (Tykerb®) (L) is an oral tyrosine kinase inhibitor of EGFR (ErbB1) and HER2 (ErbB2). This study (VEG20007) evaluated the efficacy and safety of dual pathway inhibition in patients (pts) with HER2+ adv/met breast cancer.&amp;#x2028; Methods: Eligible pts received no prior chemotherapy or HER2-directed therapy for met disease and had measurable disease per RECIST. Pts were enrolled in one of 2 cohorts. In cohort 1 (C1), pts were randomized to P 400 mg/d + L 1000 mg/d or L alone (1500 mg/d). Enrollment to cohort 2 (C2) began after completion of enrollment to C1. In C2 pts received the combination at doses of P 800 mg/d and L 1500 mg/d. Following disease assessment at week (wk) 12, pts with an objective response could continue on study treatment following re-consent; those with stable disease could continue only where trastuzumab was unavailable. The primary endpoint of C1 was progressive disease rate (PDR) at wk 12 in HER2 FISH+ pts. The primary endpoint of C2 is week 12 response rate in HER2 FISH+ pts.&amp;#x2028; Results: 140 pts were included in the randomized cohort analysis which was previously reported [J Clin Onc 26:2008 (May 20 suppl; abstr 1016)]. Enrollment in C2 has been completed; 40 pts (36 confirmed FISH+) have been enrolled. A preliminary safety analysis has been performed. The most common adverse events of any grade were diarrhea, nausea, fatigue, hypertension, and rash. The most common laboratory abnormalities were ALT and AST increase. Efficacy data will be analyzed when the last pt has completed the week 12 assessment.&amp;#x2028; Conclusion: This is the first Phase II trial to evaluate the combination of 2 oral targeted agents in first-line Her2+ adv/met breast cancer. The lower dose combination demonstrated improved response rate compared to L monotherapy. Previously unreported efficacy and safety data from the higher dose cohort will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4114.
Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages.
Authors: P W Noble, F R Lake, P M Henson, D W Riches
Journal: Journal of Clinical Investigation (1993)

Macrophages participate in inflammatory and repair processes in part through the selective release of cytokines that contribute to tissue remodeling. Extracellular matrix components generated at inflammatory sites may influence tissue remodeling by effects on leukocyte adherence and local cytokine production. In murine bone marrow-derived macrophages, we found that soluble hyaluronic acid stimulated IL-1 beta, TNF alpha, and insulin-like growth factor-1 (IGF-1) mRNA transcript expression as well as IGF-1 protein synthesis. Monoclonal antibodies to the hyaluronic acid receptor CD44 blocked the effects of hyaluronic acid on IL-1 beta, TNF alpha, and IGF-1 expression. TNF alpha and IL-1 beta mRNA expression preceded IGF-1 protein synthesis, and TNF alpha, but not IL-1 beta, was found to directly stimulate IGF-1. Furthermore, IGF-1 induction was dependent on endogenous TNF alpha production since IGF-1 protein synthesis was inhibited in the presence of anti-TNF alpha antiserum. In addition, IL-1 beta was found to exert a regulatory role on IGF-1 production by enhancing the TNF alpha effect. IL-1 beta and TNF alpha mRNA transcript expression as well as IGF-1 protein synthesis were also stimulated by chrysotile asbestos. Anti-CD44 antibodies had no effect whereas anti-TNF alpha antiserum blocked asbestos-stimulated IGF-1 production. These results indicate that hyaluronate activation of CD44 induces cytokine expression and macrophage-derived IGF-1 production is dependent on TNF alpha expression.
A Mirror up to Medicine
Authors: George Halperin
Journal: JAMA (1961)

The title of the book paraphrases Hamlet's instruction to the players to hold the mirror up to nature. The leaning of physicians toward literature, Dr. Nevins states in his preface, is explained by the special facilities the doctor has for studying human nature. A. C. Corcoran, the author of the volume, believes that those trained to deal with the sick have special opportunities to peer into the naked heart of man and as a result have used their experience in professional writing.  Part one begins with The First Aphorism of Hippocrates: Life is short, the art long, occasion sudden, experience fallible and judgment difficult. This is followed by brief sketches dealing with the contributions of Hippocrates, Galen, Paracelsus, Maimonides, Harvey, Locke, Sydenham, Boerhaave, Rush, and Laennec. Comments by Osler, Siegerist, Conan Doyle, and Duhamel add interest and illuminate the text. Part 2 consists of brief discourses on Greek, Jewish, and
Pharmacodynamic Studies of Beta Adrenergic Antagonism Induced in Man by Propranolol and Practolol
Authors: Gunter Bodem, H. L. Brammell, John V. Weil, Charles A. Chidsey
Journal: Journal of Clinical Investigation (1973)

The pharmacodynamic activities of two beta adrenergic antagonists, propranolol and practolol, were compared in eight hypertensive patients. The activity of each antagonist was established in relation to its blood concentration at maximal and submaximal adrenergic blockade defined by inhibition of exercise tachycardia. Maximal inhibition of exercise tachycardia was comparable with both drugs and averaged 74+/-7% of the control value during drug treatment. This inhibition was achieved with a blood concentration of 2.5+/-0.4 mug/ml practolol and 0.10+/-0.08 mug/ml propranolol. The antagonist activities of these drugs against adrenergic stimulation with isoproterenol infusion indicated a much greater relative potency of propranolol against this stimulus, and in vivo estimates of PA(2) values differed by more than 600-fold. Relative antagonist activity of practolol during isoproterenol stimulation was equivalent both at cardiac (inotropic and chronotropic) and at vascular adrenergic receptors, whereas greater antagonist activity of propranolol was observed at vascular receptors than at cardiac receptors. Thus, the activity of practolol was not limited to cardiac receptors as previously suggested. Practolol did not reduce cardiac output at any dose level and the effect on resting blood pressure was small. Both practolol and propranolol had much greater hypotensive activity during exercise. These studies have defined the differing pharmacodynamic activities on the cardiovascular system of two effective beta adrenergic receptor antagonists and have established the blood levels of these antagonists necessary to achieve effective adrenergic blockade.
Consultation starts on how to reveal payments from industry to doctors
Authors: N. Hawkes
Journal: BMJ (2013)

A consultation has been launched on the best way to disclose payments made by the drug industry to individual doctors or to other health professionals in the United Kingdom. The likely outcome is a single searchable database, accessible to all, that would list all payments made for whatever purpose and would name the recipients.

Payments would include funding for clinical trials; fees for advice, consultancy, lectures, and educational activity; and the costs of foreign trips to conferences, for example. The drug industry has already announced its intention to disclose the total amounts paid and the number of healthcare professionals who benefited, beginning this spring. …
Modality and abstract concepts
Authors: Fred Adams, Kenneth Campbell
Journal: Behavioral and Brain Sciences (1999)

Our concerns fall into three areas: (1) Barsalou fails to make clear what simulators are (vs. what they do); (2) activation of perceptual areas of the brain during thought does not distinguish between the activation's being constitutive of concepts or a mere causal consequence (Barsalou needs the former); and (3) Barsalou's attempt to explain how modal symbols handle abstraction fails.
Medical Schools and Immunization Policies: Missed Opportunities for Disease Prevention
Authors: Gregory A. Poland, Kristin L. Nichol
Journal: Annals of Internal Medicine (1990)

To describe current immunization requirements and policies in North American medical schools both at matriculation and before students begin clinical clerkships.Survey of all allopathic medical schools in the United States and Canada.One hundred and fifteen medical schools.Twenty-eight percent of medical schools had no immunization requirements for matriculating medical students. Thirty-one percent of the schools had no rubella immunity requirement, 40% had no measles immunity requirement, and 44% had no polio immunity requirement for matriculating students. For students beginning clinical clerkships, 18%, 35%, and 40% of schools did not require rubella, measles, and polio immunity, respectively. Only 19% and 4% of schools required hepatitis B and influenza immunizations, respectively, at any time during training. Between 20% and 30% of schools accepted student self-report as evidence of rubella and measles immunity.Despite expert guidelines, current medical school immunization policies for matriculating medical students are inadequate. Methods to assess, monitor compliance with, and facilitate student immunization are needed. Medical schools should review their immunization policies to comply with published guidelines.
Age-Specific Trends in Incidence of Noncardia Gastric Cancer in US Adults
Authors: William F. Anderson
Journal: JAMA (2010)

FOURTHmost common type of cancer and the second most common among cancer deaths worldwide. 1While tumors of the cardia, the upper part of the stomach adjoining the esophagus, may be related to gastroesophageal reflux, the majority of noncardia gastric cancers are attributable to chronic mucosal infection by the bacterium Helicobacter pylori. 2 The presumed mechanism of carcinogenesis is the induction of inflammation and consequent gastritis, the initial lesions in a multistage process. 3In both high-and low-prevalence populations, H pylori infection is commonly acquired in childhood and generally not later.In the United States, prevalence of infection increases with age, reflecting improvements in hygienic conditions and decreased crowding during childhood for younger generations. 4Prevalence also varies by race, socioeconomic status, and geographic region, 5 contributing to population differences in gastric cancer risk. 6part from H pylori infection, nutritional exposures are implicated as risk factors for noncardia gastric cancer.Consumption of salt and salt-preserved foods is associated with increased incidence, whereas consumption of fresh fruits and vegetables is protective. 7Thus, mod-ern practices of food preservation and refrigeration have favorably influenced components of diet associated with gastric cancer risk.Overall, gastric cancer incidence has steadily declined in many countries over the past 50 years or longer.However, overall trends may mask important age-specific differences. 8Furthermore, the overall decline runs counter to the subsite-specific rise in cardia cancers that may be related to obesity and gastroesophageal reflux. 9We therefore analyzed US population-based agespecific data for noncardia gastric cancer.
Doctors urge hospitals to adopt national system for scoring acutely ill patients
Authors: Z. Kmietowicz
Journal: BMJ (2012)

The launch of the national early warning score (NEWS) for adults this week by the Royal College of Physicians has been welcomed by doctors in acute medicine who are urging hospitals to embrace the system.1 2

The NEWS is the first national system for scoring acutely ill patients in the world. It has been developed by the Royal College of Physicians after detailed analysis of many of the hundreds of early warning scoring scores currently used in the NHS, including a systematic review3 and consultation with clinicians and nurses. It has the potential to dramatically improve clinical outcomes by recognising rapidly deteriorating patients and triggering an appropriate response, says the college.

Speaking at the launch of NEWS at a press conference in London Bryan Williams, chair of the working party behind the system and professor of medicine at University …
Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche
Authors: Akifumi Ootani, Xingnan Li, Eugenio Sangiorgi, Quoc T Ho, Hiroo Ueno, Shuji Toda, Hajime Sugihara, Kazuma Fujimoto, Irving L Weissman, Mario R Capecchi, Calvin J Kuo
Journal: Nature Medicine (2009)
Evaluation and management guidelines
Authors: G. Dunea
Journal: BMJ (1998)

Last year the Health Care Financing Administration issued new rules indicating how doctors must document the services for which they are billing Medicare. The guidelines define four levels of service: problem focused; expanded problem focused; detailed; and comprehensive. For each level there are detailed instructions on how to document the chief complaint, present illness, review of systems, and past, family, or social history. Each history of the present illness is defined as a chronological description which may include one or more of the following elements: location, quality, severity, timing, context, modifying factors, and associated symptoms and signs. The lowest level requires three …
Challenges of private provision in the NHS
Authors: Rachel Aldred
Journal: BMJ (2005)

Editor—Timmins's argument that the NHS has never been exclusively “public sector” is misleading.1 It obscures the astonishing growth and concentration of corporate power in the health sector. When the NHS was created, pharmaceutical companies were in their infancy, whereas today they rank among the most powerful corporations in the world.

Throughout the NHS's history, most general practitioners have been independent contractors. However, the BMA's survey of general practitioners' opinion in 2001 showed that most doctors now see themselves as part of the NHS and do not want a greater role for private companies in primary care.2 Even “entrepreneurial” doctors are hardly in the same league as multinational private firms.

The involvement of big business is already damaging the NHS. The private finance initiative (PFI) and its latest incarnation, local improvement finance trust (LIFT), hand over control of hospitals and surgeries to private consortia, which view them not primarily as health facilities but as opportunities to make money.

As large private companies take on more and more NHS services, they are likely to want to find additional revenue by increasing user charges. Greater private provision will come to undermine public funding through taxation. The government wants primary care trusts to become purely commissioning bodies, purchasing health care on behalf of a defined population. This makes them effectively “social insurers,” and it may not be long before private insurance companies are invited to compete, perhaps justified by reference to EU trade rules.

PFI providers will increasingly link up with the private health care companies now running independent service treatment centres, creating giant monopolies, complex subcontracting chains, and deals shrouded in “commercial confidentiality.” It will then be extremely difficult for the public sector to intervene, even when public safety may be at stake. The planning function of the NHS will be eroded: it will not only be fragmented but its hands will also be tied by long term, immensely complicated contracts. The BMJ has a responsibility to take a position on what may be the slow death of the NHS.
Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator.
Authors: R L Silverstein, L L Leung, P C Harpel, R L Nachman
Journal: Journal of Clinical Investigation (1984)

Thrombospondin (TSP), a multifunctional alpha-granule glycoprotein of platelets, binds fibrinogen, fibronectin, heparin, and histidine-rich glycoprotein and thus may play an important role in regulating thrombotic influences at vessel surfaces. In this study we have demonstrated that purified human platelet TSP formed a complex with purified human plasminogen (Plg). Complex formation was detected by rocket immunoelectrophoresis of mixtures of the purified radiolabeled proteins. Significant complex formation of fluid-phase Plg with adsorbed TSP was also demonstrated by enzyme-linked immunosorbent assay (ELISA). The complex formation was specific, saturable, and inhibited by excess fluid-phase TSP, with an apparent KD of approximately 35 nM. In both ELISA and rocket immunoelectrophoresis systems, complex formation was inhibited by 10 mM epsilon-amino-n-caproic acid, implying that there is a role for the lysine binding sites of Plg in mediating the interaction. TSP also formed a complex with plasmin as detected by ELISA but did not directly inhibit plasmin activity measured with a synthetic fluorometric substrate or with a 125I-fibrin plate assay. TSP, when incubated with Plg before addition to 125I-fibrin plates significantly inhibited the generation of plasmin activity by tissue plasminogen activator (TPA) in a manner that was calcium dependent. A kinetic study of Plg activation by TPA in the presence of TSP demonstrated that Michaelis-Menten kinetics were followed and that TSP acted as a noncompetitive inhibitor. These studies support the hypothesis that TSP, acting as a multifunctional regulator in focal areas of active hemostasis, could serve as a prothrombotic influence, leading to increased deposition of fibrin.