tbuckley/cabot-search huggingface dataset:
European Medicines Agency tightens rules on conflict of interest
Authors: D. Cohen
Journal: BMJ (2010)

The European Medicines Agency has launched much stricter rules for its experts’ interaction with the drug industry.

The agency’s new guidance on conflicts of interest says that people who have financial interests in a company or who consult or are a member of a company’s advisory board will have their work with the agency severely restricted.

People will be asked to fill in a declaration of interests form and will be assigned a “risk” score that is based on their links with industry. The agency will also consider whether an expert’s institution receives money from a company or whether the expert is an investigator on …
Increased energy expenditure in Parkinson's disease.
Authors: S Levi, M Cox, M Lugon, M Hodkinson, A Tomkins
Journal: BMJ (1990)

tinues to carry a greater risk of psychiatric disturbance.It cannot be assumed from present evidence that the findings of this study are a consequence of current practice in haemophilia care, although it may well be so.Only after further investigation will it be possible to determine clinical policies and deploy resources on the basis of accurate information about children's needs.
The effect of vasodilator therapy on the clinical outcome of patients with primary pulmonary hypertension.
Authors: S Rich, B H Brundage, P S Levy
Journal: Circulation (1985)

The short- and long-term hemodynamic effects of vasodilators in patients with primary pulmonary hypertension have been studied, but whether they affect survival is unknown. We measured the short-term response to nifedipine and hydralazine in 23 patients with primary pulmonary hypertension and followed their clinical course over 2 years. A favorable drug response, defined as a fall in the pulmonary vascular resistance of 20% or greater, occurred in 18 patients (78%). Half of the patients who exhibited a favorable short-term response were treated with long-term vasodilator therapy. Their clinical course was compared with that of responders who were not treated and with that of the nonresponders. Of the responders who were treated, two improved, four had no change, and three died; of the responders who were not treated, one improved, three had no change, and five died. Using stepwise Cox regression, we evaluated age, sex, functional class on entry, pulmonary arterial pressure, pulmonary vascular resistance, and short-term drug response as predictors of survival and found only functional class and a favorable short-term drug response to be significant predictors (p less than .01); however, there was no difference in survival between the responders who were treated and those who were not. We conclude that the ability to respond to short-term nifedipine or hydralazine therapy predicts longer survival for patients with primary pulmonary hypertension, but placing patients with a favorable short-term response on long-term vasodilator therapy does not affect the overall outcome.
Are There Unidentified Factors in the Control of Aldosterone Secretion?
Authors: James O. Davis
Journal: New England Journal of Medicine (1972)

During the last decade, a substantial amount of evidence has accumulated to show that there are at least four factors involved in the regulation of aldosterone secretion. These include the primary regulatory mechanism, the renin-angiotensin system, ACTH and the plasma concentrations of sodium and potassium. In recent years, investigators have continued to search for additional factors that might be involved. Anephric man provides a useful model in which to look for extrarenal control mechanisms for aldosterone secretion, and several groups of investigators1 , 2 have studied the factors that influence the plasma aldosterone level in this model. Another study is described in . . .
Diapers and Poisons
Authors: Barry H. Rumack
Journal: JAMA (1982)

Those of us with experience in childhood poisoning have published numerous articles dealing with series of cases related to a single intoxicant. While these series and others that show various epidemiologic data abound in the literature and in textbooks, few articles deal with practical poison prevention. We usually include a paragraph or two on prevention in review articles or general poisoning principles.  Some hazardous household areas may even be pointed out. Specific data for these areas are usually related to where the products are thought to be found—garages, kitchen sinks, laundry rooms, or medicine cabinets.  The clear-cut data by McCormick et al (p 2159) show us that wherever diaper changing is done must be classified as potentially hazardous. The article was done looking specifically at the area and not by looking at the products and surmising where they might have been located. Reasons for a certain area being high risk
Dogger Bank Itch: Survey of Trawlermen
Authors: M. L. Newhouse
Journal: BMJ (1966)

Cerebral Berry Aneurysms-Cromnpton MEDIBALlJURNALThe critical size-that is, the size beyond which aneurysms suddenly become unstable and likely to rupture-was a maxi- mum external diameter of 4 mm.Aneurysms can probably form or begin at any age and may enlarge and rupture rapidly.In patients with multiple aneurysms the largest aneurysm had ruptured in 88%.When combinations of middle cerebral and internal carotid aneurysms were present on the same side the proximal aneurysm was more often ruptured.Infiltration of the wall of the aneurysm with white blood cells and fibrin was thought to precede enlargement or rupture.This was thought to be due to endothelial damage as a result of pulsation, turbulent flow, or ischaemia resulting from mural thrombosis.
Health secretary says new commissioning board's first job will be to devolve powers to local groups
Authors: N. Hawkes
Journal: BMJ (2012)

Andrew Lansley, the health secretary, has restated his vision for the reform of the NHS in England in a letter to the chairman of the NHS Commissioning Board Authority.

It makes clear that the board’s function, when it is established in October, will not be to acquire power for itself but to devolve it to clinical commissioning groups (CCGs).

Ever since the board was first proposed, and more so since David Nicholson, chief executive of the NHS in England, was named as its chief executive, there has been a tension between Lansley’s original plan to devolve power locally and the increasing acquisition of responsibilities by the board.

Backers of the reforms feared that this was the old NHS …
The transcription factor IRF1 dictates the IL-21-dependent anticancer functions of TH9 cells
Authors: Frédérique Végran, Hélène Berger, Romain Boidot, Grégoire Mignot, Mélanie Bruchard, Magalie Dosset, Fanny Chalmin, Cédric Rébé, Valentin Dérangère, Bernhard Ryffel, Masashi Kato, Armelle Prévost-Blondel, François Ghiringhelli, Lionel Apetoh
Journal: Nature Immunology (2014)
Re: Camillo Porta, Emiliano Calvo, Miguel A. Climent, et al. Efficacy and Safety of Everolimus in Elderly Patients With Metastatic Renal Cell Carcinoma: An Exploratory Analysis of the Outcomes of Elderly Patients in the RECORD-1 Trial. Eur Urol 2012;61:826–33
Authors: Giuseppe Procopio, Elena Verzoni, Filippo De Braud
Journal: European Urology (2012)
Cytochrome b evolution in birds and mammals: an evaluation of the avian constraint hypothesis
Authors: S. E. Stanley, R. G. Harrison
Journal: Molecular Biology and Evolution (1999)

Patterns of molecular evolution in birds have long been considered anomalous. Compared with other vertebrates, birds have reduced levels of genetic divergence between groups of similar taxonomic ranks for a variety of nuclear and mitochondrial markers. This observation led to the avian constraint hypothesis, which identifies increased functional constraint on avian proteins as the cause for the reduction in genetic divergence. Subsequent investigations provided additional support for the avian constraint hypothesis when rates of molecular evolution were found to be slower in birds than in mammals in a variety of independent calibrations. It is possible to test the avian constraint hypothesis as an explanation for this avian slowdown by comparing DNA sequence data from protein-coding regions in birds and homologous regions in mammals. The increased selective constraints should lead to a reduction in the proportion of amino acid replacement substitutions. To test for such a decrease, we calculated the numbers of amino acid replacement substitutions per replacement site (dN) and silent substitutions per silent site (dS) for the complete mitochondrial cytochrome b gene using 38 avian and 43 mammalian comparisons that were phylogenetically independent. We find that dN/dS is significantly smaller in birds than in mammals. This difference cannot be explained by differences in codon bias affecting dS values. We suggest that the avian slowdown can be explained, at least in part, by a decreased tolerance for amino acid substitutions in avian species relative to mammalian species.
Molecular Evolutionary Convergence of the Flight Muscle Protein Arthrin in Diptera and Hemiptera
Authors: S. Schmitz
Journal: Molecular Biology and Evolution (2003)

Uniquely, the asynchronous flight muscle myofibrils of many insects contain arthrin, a stable 1:1 conjugate between actin and ubiquitin. The function of arthrin is still unknown. Here we survey for the presence of arthrin in 63 species of insect across nine orders using Western blotting. Analysis of the evolutionary distribution shows that arthrin has evolved a limited number of times but at least once in the Diptera and once in the Hemiptera. However, the presence of arthrin does not correlate with any observed common features of flight mechanism, natural history, or morphology. We also identify the site of the isopeptide bond in arthrin from Drosophila melanogaster (Diptera) and Lethocerus griseus (Hemiptera) using mass spectrometry. In both species, the isopeptide bond is formed between lysine 118 of the actin and the C-terminal glycine 76 of ubiquitin. Thus, not only the ubiquitination of actin but also the site of the isopeptide bond has evolved convergently in Diptera and Hemiptera. In terms of the actin monomer, lysine 118 is near neither the binding sites of the major actin-binding proteins, myosin, tropomyosin, or the troponins, nor the actin polymerization sites. However, molecular modeling supports the idea that ubiquitin bound to an actin in one F-actin strand might be able to interact with tropomyosin bound to the actin monomers of the other strand and thereby interfere with thin filament regulation.
The Debt and the Cash Flow of Residents: I. The Grim Present
Authors: Brian J. Bohlmann
Journal: JAMA (1990)

To the Editor.—  I read with great interest the recent article by Hernried et al 1 regarding medical students' indebtedness. The increasing importance of this issue is not fully appreciated by many observers, including some among the medical community. I recently completed my internal medicine residency at the Marshfield Clinic in Marshfield, Wis. I have only a moderate debt load and am fortunate because the cost of living here in a rural area is less than that associated with large metropolitan centers. Nonetheless, even as a single person, I am just able to pay for food, housing, and transportation, and I have little left over at the end of the month. I have no doubt that those residents who are married and/or have children find it difficult to provide even basic necessities, especially in parts of the country where the cost of living is high.  The issue of residents'
Acute tendinitis and arthritis. A presenting symptom of familial type II hyperlipoproteinemia
Authors: C. J. Glueck
Journal: JAMA (1968)

Achilles tendinitis and tenosynovitis, sometimes accompanied by arthritis, were common presenting symptoms in 14 patients from 9 different kindreds with familial type II hyperlipoproteinemia. Attacks occurred 4 to 12 times per year, lasted two to three days, occurred unilaterally and bilaterally, and recurred over spans of up to 40 years without joint deformity or loss of motion. Appearance of symptoms in the midteens in the majority of patients provides an opportunity for early diagnosis, family screening, and therapy in this inherited disorder associated with accelerated coronary atheromatosis.
Glutamate transporters in glial plasma membranes: Highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry
Authors: Farrukh A. Chaudhry, Knut P. Lehre, Menno van Lookeren Campagne, Ole P. Ottersen, Niels C. Danbolt, Jon Storm-Mathisen
Journal: Neuron (1995)
THE FACTOR DETERMINING THE SPREAD OF RED MARROW DURING ANEMIA
Authors: Philip D. McMaster, Herbert Haessler
Journal: The Journal of Experimental Medicine (1921)

Rabbits in which a chronic anemia of moderate grade is induced by repeated bleedings repair the hemoglobin loss much more rapidly when given subcutaneous injections of hemoglobin than when this is not the case. But the effect of the injections is not manifest for several weeks, during which many pale corpuscles are put out by the marrow; whence it follows that the introduced pigment does not find its way in quantity direct to the new-formed cells but must follow a more or less roundabout metabolic route, perhaps the same one as that of ordinary iron compounds destined for the blood. The rapid replacement of the circulating hemoglobin in the injected animals occurs chiefly through an increased production of corpuscular substance having the same color index as that found in uninjected, anemic controls. By color index in this connection is meant the relation of hemoglobin to the volume of the massed corpuscles. Late in the period of bleedings and hemoglobin injections the demand for stroma for the new-formed blood is far greater than in control animals that have been merely bled, yet the circulating corpuscles show no lessening in resistance to salt solution, such as might perhaps be expected were there a stroma lack. The hematopoietic tissue of the injected animals undergoes an extensive increase-a fact which speaks strongly for the view that the elements out of which stroma is formed are still abundant. The factor which determines the spread of red marrow during anemia is shown by our experiments to be the presence in the body of hemoglobin, or perhaps of its precursors, in excess of the amount which can be utilized by the marrow already existing. Numerous illustrations in support of the point can be adduced from human pathology. Two will suffice. The widespread "currant jelly" marrow of pernicious anemia is found in an organism rendered anemic but supplied with hemoglobin in excess; while the pale, restricted marrow of cases suffering from chronic anemia due to repeated hemorrhages is associated with depletion of the constituents necessary for pigment production.
Elaboration of type b capsule by Haemophilus influenzae as a determinant of pathogenicity and impaired killing by trimethoprim-sulfamethoxazole.
Authors: R Yogev, E R Moxon
Journal: Journal of Clinical Investigation (1982)

In vitro, Haemophilus influenzae strains have two distinct patterns of susceptibility to trimethoprim-sulfamethoxazole (TMP/SMZ); strains with low minimum inhibitory concentration and high minimum bactericidal concentration (tolerant) and those with both low minimum inhibitory concentration and minimum bactericidal concentration (kill-sensitive). Tolerant H. influenzae strains were found to elaborate significantly more type b capsular polysaccharide, a linear polymer of ribosyl ribose phosphate (PRP), than kill-sensitive strains. Tolerant strains became susceptible to killing by TMP/SMZ when type b capsule was physically removed, but reacquired tolerance following growth and reversion to original (mucoid) phenotype. Susceptibility of wild (type a, b, c), isogenic (type b and untypable), and transformed (type b and d) strains indicated that elaboration of type b capsule was associated with TMP/SMZ tolerance. In a second series of studies, virulence of H. influenzae in the infant rat model was correlated with in vitro tolerance. Tolerant strains (13/13) caused systemic disease while none (0/7) of kill-sensitive strains were pathogenic. The efficacy of TMP/SMZ in the treatment of invasive infection was evaluated in rats with established bacteremia and meningitis. TMP/SMZ failed to eradicate H. influenzae b from the blood in 85% (17/20) or from the cerebrospinal fluid in 95% (19/20) of infected animals. Thus, in vitro tolerance correlated with therapeutic failure in vivo.
THROMBOPENIA AND INCREASED CAPILLARY FRAGILITY IN HEPATIC DISEASE
Authors: FRANK B. WHITESELL
Journal: JAMA (1949)

Despite the fact that the hemorrhagic state existing in hepatic disease has been known for several centuries, no entirely satisfactory explanation for it had been advanced until the demonstration of a prothrombin defect in 1935 by Quick and others.<sup>1</sup>While hypoprothrombinemia bears unquestioned responsibility for the hemorrhagic tendency in obstructive jaundice, many students of the subject are unwilling to assign it the sole responsibility for all the instances of bleeding encountered in parenchymal disease of the liver. This has led to an extensive search for other factors associated with hepatic disease which may affect coagulability of the blood. Recently, emphasis has been placed on the demonstration of a circulating anticoagulant, presumed to be heparin. Its place in the hemorrhagic phenomena associated with hepatic disease as yet remains obscure. It is the purpose of this presentation to emphasize two neglected factors which may be associated with coagulation defects in hepatic
Longitudinal Screening for Prostate Cancer With Prostate-Specific Antigen
Authors: Deborah S. Smith
Journal: JAMA (1996)

To determine for the first 4 years of serial prostate-specific antigen (PSA)-based screening trends in compliance, prevalence of abnormal screening test results, cancer detection rates, and stage and grade of cancers detected.A community-based study of serial screening for prostate cancer with serum PSA measurements.University medical center.A total of 10 248 male volunteers at least 50 years old who were screened at 6-month intervals for a minimum of 48 months.The proportion of men who returned for serial screening, the proportion with elevated PSA levels, the proportion with newly elevated PSA levels, prostate cancer detection rates, and the distribution of tumor stages and grades at diagnosis.At 48 months, 79% of volunteers returned for screening. During this interval there was a decrease in the proportion of volunteers with serum PSA levels higher than 4.0 ng/mL (from 10% to 6%-7%), in cancer detection rates (from 3% to <1%), and in the proportion with clinically advanced cancer (from 6% to 2%). In men who underwent surgery, the proportion with high-grade cancer decreased (from 11% to 6%), and the proportion with pathologically advanced cancer was proportionately reduced but not significantly reduced (from 33% to 27%).With serial PSA-based screening, the proportion of men with abnormal test results decreased, and the prostate cancer detection rate decreased to near the reported population-based incidence rate. There was also a shift to detection of cancers at an earlier clinical stage and detection of lower-grade cancers. If PSA screening is ultimately shown to be beneficial, then appropriate cost-benefit analyses will be required to determine how the shifts in cancer detection rate and cancer stage will affect the economics of serial PSA-based screening.
Adverse Reactions to Phenothiazines
Authors: Leo E. Hollister
Journal: JAMA (1964)

PHENOTHIAZINE derivatives are classic examples of the fact that few drugs have just one effect. Although we commonly think of these agents as clinically useful in the treatment of emotional disorders, especially schizophrenic reactions, they also have medical importance as antiemetic agents and as adjuncts to anesthetic or analgesic drugs (Table 1). In addition to these useful therapeutic effects, various phenothiazine derivatives may exhibit antihistaminic, adrenergic blocking, anticholinergic, or metabolic-endocrine actions. Such an array of pharmacodynamic actions contributes to the wide variety of adverse effects that these drugs may evoke. These complications, which have been reviewed in detail, are summarized in Table 2.<sup>1-3</sup> <i>Adverse behavioral effects</i>are sometimes seen, even though most drugs in this class are useful as antipsychotic agents. In general, the rule seems to be that the more seriously disturbed the patient, the better these drugs are tolerated. Patients with mild anxiety usually tolerate small doses
Evidence for a coordinate role of CD14+ antigen-presenting cells and regulatory T cells in conditioning the microenvironment of metastatic lymph nodes from patients with cervical cancer
Authors: Marijne Heeren, Bas Koster, Sanne Samuels, Debbie Ferns, Dafni Chondronasiou, Gemma Kenter, Ekaterina S Jordanova, Tanja D de Gruijl
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts A better understanding of the microenvironment in relation to lymph node metastasis is essential for the development of effective immunotherapeutic strategies against cervical cancer. In the present study, we investigated the microenvironment of tumor-draining lymph nodes of
Ibuprofen and hydrogel-released ibuprofen in the reduction of inflammation-induced migration in melanoma cells
Authors: M. Redpath, C.M.G. Marques, C. Dibden, A. Waddon, R. Lalla, S. MacNeil
Journal: British Journal of Dermatology (2009)

There is growing evidence that inflammation may exacerbate cancer metastasis and several clinical studies show that taking nonsteroidal anti-inflammatory drugs appears to reduce metastases.The aims of this study were: (i) to examine the effects of ibuprofen on the major proinflammatory cytokine tumour necrosis factor (TNF)-alpha induction of migration of C8161 and HBL human melanoma cells; (ii) to develop ibuprofen-releasing hydrogels (Pluronics F127) for future topical use in reducing metastatic spread of primary melanoma; and (iii) to examine whether the actions of ibuprofen might be explained by induction of apoptosis.Melanoma cells were exposed to 300 U mL(-1) TNF-alpha for a 24-h period prior to making a scratch wound to which ibuprofen or ibuprofen-loaded hydrogels were then added. The effects of relevant concentrations of ibuprofen on cell viability and apoptosis were examined.Ibuprofen at 10(-3) mol L(-1) significantly reduced TNF-alpha-stimulated migration of both cell types to that of nonstimulated cells (P < 0.001). TNF-alpha-unstimulated cell migration was not significantly affected. Cells responded similarly to SS and SR forms of ibuprofen. Cells treated with ibuprofen sodium salt-loaded hydrogels showed a significant reduction in migration when compared with unloaded hydrogels. Ibuprofen induced apoptosis in HBL cells but had no effect on C8161 melanoma cells apoptosis at concentrations that reduced migration.These results demonstrate that TNF-alpha upregulated malignant melanoma migration in vitro and that this could be reduced by ibuprofen both in solution and delivered from a hydrogel. These effects of ibuprofen cannot be attributed simply to induction of apoptosis.
Impact Of The Frankfurt HAE Therapy Protocol On Health-Related Quality Of Life (HRQoL) In 50 Patients With Hereditary Angioedema (HAE)
Authors: W. Kreuz, I. Martinez-Saguer, E. Rusicke, E. Aygören-Pürsün, T. Klingebiel
Journal: Journal of Allergy and Clinical Immunology (2009)