tbuckley/cabot-search huggingface dataset:
Effects of a Potent Platelet-activating Factor Antagonist, SR27417A, on Allergen-induced Asthmatic Responses
Authors: DAVID J. EVANS, PETER J. BARNES, MARC CLUZEL, BRIAN J. O'CONNOR
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Platelet-activating factor (PAF) is a lipid-derived mediator that has been implicated in the pathophysiology of airway inflammation in asthma. Its actions include chemotaxis and activation of inflammatory cells, particularly eosinophils. Inhaled PAF causes bronchoconstriction and increased airway responsiveness in human subjects. However, PAF antagonists have so far failed to show benefits in allergen challenge or in the treatment of chronic asthma. SR27417A is a novel PAF antagonist with increased potency compared with previously tested compounds. Twelve asthmatic subjects received treatment with either SR27417A or placebo for 1 wk in a double-blind crossover study. After treatment each subject underwent allergen challenge. Effects were assessed in terms of early and late asthmatic responses and allergen-induced effects on airway responsiveness. Baseline lung function and airway responsiveness were also examined. Treatment with SR27417A significantly attenuated the late asthmatic response (AUC LAR4–10h: 107 ± 24 after placebo, 79 ± 17 after SR27417A, p < 0.05; mean maximal percent fall in FEV1 LAR: 29 ± 6% after placebo, 23.5 ± 5.4% after SR27417A, p < 0.05). There were no effects on early asthmatic responses, allergen-induced airway responsiveness, or baseline lung measurements. SR27417A is the most potent PAF antagonist to date, and it has a modest inhibitory effect on the late asthmatic response. This suggests that PAF has a small role in allergic inflammation.
Genetic Studies on Rheumatoid Arthritis
Authors: J. S. Lawrence, J. Ball
Journal: Annals of the Rheumatic Diseases (1958)

Though there has been much speculation on the causes of rheumatoid arthritis, the fundamental mechanism remains obscure.There have, however, been indications that a hereditary factor is present (Falls, 1953).Kroner reported four generations of rheumatoid arthritis in one family, the disease being apparently transmitted by the females.Papp and Tepperberg (1937), in another family, recorded eleven persons with rheumatoid arthritis in four generations.Kaufmann and Scheerer (1928) found a greater concordance in monozygotic than in dizygotic twins.Short, Abrams, and Sartwell (1952) recorded a prevalence of 12 per cent. in rheumatoid arthritic families, but of only 5 per cent. in controls and in the series of Stecher, Solomon, and Wolpaw (1952), the prevalence was 5 and 0 1 per cent. in rheumatoid families and controls respectively.In the Empire Rheumatism Council's Report on aetiological factors in rheuma- toid arthritis (Lewis-Faning, 1950), 7 per cent. of the fathers of patients as compared with 3 per cent. of copyright.
Concentrations of Idoxuridine in Serum, Urine, and Cerebrospinal Fluid of Patients with Suspected Diagnoses of Herpesvirus hominis Encephalitis
Authors: A. Martin Lerner, Elizabeth Jane Bailey
Journal: Journal of Clinical Investigation (1972)

A reproducible microbiologic assay of microgram quantities of idoxuridine (IDU) in serum, urine, or cerebrospinal fluid is presented. The antiviral assay is not interfered with by type-specific antibody or interferon. During slow intravenous infusions of idox-uridine (4 mg/min) in patients with suspected diagnoses of Herpesvirus hominis encephalitis, the rate of inactivation and/or removal of drug exceeded its administration. During several rapid infusions of idoxuridine (50 mg/min) significant quantities of the drug were found in serum, urine, and cerebrospinal fluid. Idoxuridine is not significantly bound to serum proteins and is not deiodinated in fresh serum or urine in vitro to inactive products (iodouracil, uracil, iodide). It is rapidly excreted into the urine. Inactivation of IDU occurs in tissues. This antiviral assay of IDU in body fluids should be applicable to other viruses and potential antiviral agents.
Potentiation of human immunoglobulin E synthesis by plasma immunoglobulin E binding factors from patients with the hyperimmunoglobulin E syndrome.
Authors: D Y Leung, R Frankel, N Wood, R S Geha
Journal: Journal of Clinical Investigation (1986)

Affinity-purified IgE-binding factors from the plasma of patients with the hyper IgE syndrome (HIE) were assessed for their capacity to enhance IgE synthesis by B cells derived from patients with allergic rhinitis or normal nonatopic donors. IgE-binding factors from three of four HIE patients enhanced IgE synthesis by B cells from patients with perennial allergic rhinitis, or with seasonal allergic rhinitis (SAR) and recent pollen exposure, but did not enhance IgE synthesis by B cells from nonatopic donors or from SAR patients with no recent pollen exposure. IgG synthesis was not affected by HIE IgE binding factors. In contrast, IgE binding factors from three of three nonatopic donors failed to enhance IgE or IgG synthesis. Plasma IgE-binding factors from the fourth patient with HIE contained a mixture of IgE-potentiating activity and IgE-suppressive activity. These two activities could be separated on concanavalin A Sepharose or peanut agglutinin agarose columns. Human IgE potentiating factor, but not IgE suppressive factor, had affinity for concanavalin A but not peanut agglutinin and fractionated into two peaks on gel filtration over Sephadex G-75: one peak with a molecular size of approximately 15,000 D and the other with a molecular size of approximately 60,000 D. The isolation of functional IgE binding factors which potentiate IgE synthesis from the plasma of patients with HIE suggests that IgE-binding factors play an important role in the in vivo regulation of IgE synthesis in man.
Music Not Only Has Charms to Soothe, But Also to Aid Elderly in Coping With Various Disabilities
Authors: Teri Randall
Journal: JAMA (1991)

ALTHOUGH illnesses vary, very patient at the geriatric day hospital at The University of Texas Medical Branch (UTMB), Galveston, receives one therapy in common.  This therapy is unusual in that it elicits immediate and positive effects in nearly all who receive it and has virtually no contraindications. Furthermore, it costs little more than a song because it is precisely that: a song.  I'm in heaven when we're dancing cheek to cheek, Louis Armstrong and Ella Fitzgerald croon. As the tune emanates from the music therapist's portable tape player, 20 geriatric patients seated in two large circles reach out to pat their neighbors' shoulders, look in each others' eyes, and smile.  Music for Mobility, Analgesia  In what is probably the highlight of their day at this specialized facility (one of only a handful of geriatric day hospitals in the United States [see accompanying article]) these patients are about to begin a
Use of Expert Panels to Define the Reference Standard in Diagnostic Research: A Systematic Review of Published Methods and Reporting
Authors: Loes C. M. Bertens, Berna D. L. Broekhuizen, Christiana A. Naaktgeboren, Frans H. Rutten, Arno W. Hoes, Yvonne van Mourik, Karel G. M. Moons, Johannes B. Reitsma
Journal: PLoS Medicine (2013)

Background In diagnostic studies, a single and error-free test that can be used as the reference (gold) standard often does not exist. One solution is the use of panel diagnosis, i.e., a group of experts who assess the results from multiple tests to reach a final diagnosis in each patient. Although panel diagnosis, also known as consensus or expert diagnosis, is frequently used as the reference standard, guidance on preferred methodology is lacking. The aim of this study is to provide an overview of methods used in panel diagnoses and to provide initial guidance on the use and reporting of panel diagnosis as reference standard. Methods and Findings PubMed was systematically searched for diagnostic studies applying a panel diagnosis as reference standard published up to May 31, 2012. We included diagnostic studies in which the final diagnosis was made by two or more persons based on results from multiple tests. General study characteristics and details of panel methodology were extracted. Eighty-one studies were included, of which most reported on psychiatry (37%) and cardiovascular (21%) diseases. Data extraction was hampered by incomplete reporting; one or more pieces of critical information about panel reference standard methodology was missing in 83% of studies. In most studies (75%), the panel consisted of three or fewer members. Panel members were blinded to the results of the index test results in 31% of studies. Reproducibility of the decision process was assessed in 17 (21%) studies. Reported details on panel constitution, information for diagnosis and methods of decision making varied considerably between studies. Conclusions Methods of panel diagnosis varied substantially across studies and many aspects of the procedure were either unclear or not reported. On the basis of our review, we identified areas for improvement and developed a checklist and flow chart for initial guidance for researchers conducting and reporting of studies involving panel diagnosis. Please see later in the article for the Editors' Summary
ABC of resuscitation. The airway at risk.
Authors: R S Simons, T H Howells
Journal: BMJ (1986)

Failure to maintain a patent airway is a common cause ofavoidable death in unconscious patients.The principles ofairway management after cardiac arrest are the same as those used during anaesthesia or resuscitation after major trauma.Patency of the airway may be impaired by loss of normal muscle tone or by obstruction, including contamination by foreign material ,__ _from the mouth, nasopharynx, oesophagus, or stomach. Airway clearance Opening the airwayIn the unconscious patient relaxation of the tongue, neck, and pharyngeal muscles causes soft tissue obstruction of the supraglottic airway.Correction using long established manoeuvres includes head tilt and jaw lift or jaw thrust.The use of neck lift to produce head tilt is widely recommended in first aid manuals, but it leaves one hand committed behind the neck and it Neck lift.may be dangerous in the presence ofan unstable injury of the cervical spine.Head tilt will relieve obstruction in 80% ofpatients and jaw lift or jaw thrust will further improve overall patency but tends to oppose the lips.In some of these patients airway obstruction may persist, particularly during expiration, probably because of nasal airway obstruction caused by a "flap-valve" effect of soft palate and nasopharyngeal tissues, as in the snoring subject.The triple manoeuvre (Safar) requires the rescuer to open the mouth Xaw lilt.Jaw thrust.while performing head tilt and jaw thrust.It is difficult to maintain Jaw lil ii Jaw thrust.especially when performing artificial respiration at the same time.
Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis: 2-year results of a randomised trial
Authors: Rachel B Jones, Shunsuke Furuta, Jan Willem Cohen Tervaert, Thomas Hauser, Raashid Luqmani, Matthew D Morgan, Chen Au Peh, Caroline O Savage, Marten Segelmark, Vladimir Tesar, Pieter van Paassen, Michael Walsh, Kerstin Westman, David RW Jayne
Journal: Annals of the Rheumatic Diseases (2015)

Objectives The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis at 12 months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated renal vasculitis are unknown. Methods Forty-four patients with newly diagnosed ANCA-associated vasculitis and renal involvement were randomised, 3:1, to glucocorticoids plus either rituximab (375 mg/m 2 /week×4) with two intravenous cyclophosphamide pulses (n=33, rituximab group), or intravenous cyclophosphamide for 3–6 months followed by azathioprine (n=11, control group). Results The primary end point at 24 months was a composite of death, end-stage renal disease and relapse, which occurred in 14/33 in the rituximab group (42%) and 4/11 in the control group (36%) (p=1.00). After remission induction treatment all patients in the rituximab group achieved complete B cell depletion and during subsequent follow-up, 23/33 (70%) had B cell return. Relapses occurred in seven in the rituximab group (21%) and two in the control group (18%) (p=1.00). All relapses in the rituximab group occurred after B cell return. Conclusions At 24 months, rates of the composite outcome of death, end-stage renal disease and relapse did not differ between groups. In the rituximab group, B cell return was associated with relapse. Trial registration number ISRCTN28528813.
Endothelial and Antithrombotic Actions of HDL
Authors: Chieko Mineo, Hiroshi Deguchi, John H. Griffin, Philip W. Shaul
Journal: Circulation Research (2006)

It is well recognized that high-density lipoprotein (HDL)-cholesterol is antiatherogenic and serves a role in mediating cholesterol efflux from cells. However, HDL has multiple additional endothelial and antithrombotic actions that may also afford cardiovascular protection. HDL promotes the production of the atheroprotective signaling molecule nitric oxide (NO) by upregulating endothelial NO synthase (eNOS) expression, by maintaining the lipid environment in caveolae where eNOS is colocalized with partner signaling molecules, and by stimulating eNOS as a result of kinase cascade activation by the high-affinity HDL receptor scavenger receptor class B type I (SR-BI). HDL also protects endothelial cells from apoptosis and promotes their growth and their migration via SR-BI–initiated signaling. As importantly, there is evidence of a variety of mechanisms by which HDL is antithrombotic and thereby protective against arterial and venous thrombosis, including through the activation of prostacyclin synthesis. The antithrombotic properties may also be related to the abilities of HDL to attenuate the expression of tissue factor and selectins, to downregulate thrombin generation via the protein C pathway, and to directly and indirectly blunt platelet activation. Thus, in addition to its cholesterol-transporting properties, HDL favorably regulates endothelial cell phenotype and reduces the risk of thrombosis. With further investigation and resulting greater depth of understanding, these mechanisms may be harnessed to provide new prophylactic and therapeutic strategies to combat atherosclerosis and thrombotic disorders.
Inhibition of Ileal Water Absorption by Intraluminal Fatty Acids INFLUENCE OF CHAIN LENGTH, HYDROXYLATION, AND CONJUGATION OF FATTY ACIDS
Authors: Helmut V. Ammon, Sidney F. Phillips
Journal: Journal of Clinical Investigation (1974)

The influence of fatty acids on ileal absorption of water, electrolytes, glucose, and taurocholate was examined in Thirty-Vella fistulas in five mongrel dogs. Fatty acid absorption also was measured. Segments of terminal ileum were perfused at steady state with isotonic electrolyte solutions containing 11.2 mM glucose, 4.5 mM taurocholate, and 0.1-5.0 mM fatty acid. Three C(18) fatty acids, oleic acid, 10(9)-hydroxystearic acid, and ricinoleic acid, completely inhibited water absorption at 5 mM. Sodium, chloride, and potassium absorptions were inhibited in parallel with absorption of water. Differences between the potencies of C(18) fatty acids were apparent when lesser concentrations were perfused. Dodecanoic and decanoic acids were as effective as C(18) fatty acids at 5 mM but octanoic and hexanoic acids were ineffective. The polar group of C(18) fatty acids was modified by conjugating oleic and ricinoleic acids with taurine. When these compounds and a substituted C(18) fatty acid, p-n-decylbenzenesulfonate, were perfused, water absorption was also inhibited. Short-chain fatty acids (C(3) and C(4)) and their hydroxylated derivatives were ineffective at 5 mM. When water absorption was inhibited, absorption of glucose and taurocholate was decreased. We speculate that the phenomenon of inhibition of water and electrolyte absorption by fatty acids may be relevant to steatorrhea and diarrhea in man.
Care of children in general practice.
Authors: S Carne
Journal: BMJ (1979)

When I began in general practice 25 years ago, it was held that maternity care was the foundation on which general practice was built. To a degree this is still true, except that today what matters most to the GP is not the actual delivery but the health of the child himself. In Britain one-quarter of all general practice consultations are concerned with children. GPs are consulted about children over 50 million times each year; that is 2000 consultations a year for each GP ; 40 a week, or eight each working day.
Intestinal Bleeding Caused by Hookworm
Authors: Donald E. McDowell
Journal: JAMA (1981)

<h3>To the Editor.—</h3> The article by de la Riva et al, entitled "Acute Massive Intestinal Bleeding Caused by Hookworm" (1981;246:68), called to mind the presentation that I made to the joint meeting of the Argentine and Paraguayan Surgical Societies in 1968 of seven cases of severe gastrointestinal hemorrhage owing to a heavy infestation of hookworms. These seven cases were encountered at the Baptist Hospital in Asuncion, Paraguay, where I was then serving as chief of the surgical service. The first patient treated was a 2-year-old child who was admitted with a hemoglobin level of 2 g/dL and multiple bowel movements of blood that varied from black to bright red. Sigmoidoscopy and barium enema results were normal. Examination of the fecal material for parasites showed innumerable eggs of the parasite<i>Ancylostoma</i>. Eight blood transfusions were given that only temporarily improved the child's condition. An abdominal exploration showed edema and inflammation of
Clinically significant interaction between digoxin and quinidine.
Authors: D W Holt, A M Hayler, M E Edmonds, R F Ashford
Journal: BMJ (1979)

paras), and to attend a clinic or return the questionnaire after three months.Fifty-two patients (87 %) (15 primiparas and 37 multiparas) completed questionnaires.They were matched with a control group of 52 vaccinated patients who received no hormonal treatment.The mean (i SD) number of days of postpartum bleeding was 58-5 i 18-5 in the treated patients and 20-8 1-1 in the controls.This difference was significant (P <0-001).Patients still bleeding at three months were treated with low-dose oestrogen/ progestogen pills) which invariably stopped bleeding.Only one patient was so treated before three months.Thirty-three treated patients, but only two controls, had continuous bleeding for three months.In no case was the loss heavy and no patients developed anaemia (haemoglobin less than 10-0 g/dl).
Performance of Mid Staffordshire surgeon was not deficient, panel rules
Authors: C. Dyer
Journal: BMJ (2014)

The Medical Practitioners Tribunal Service has rejected allegations by the General Medical Council that a surgeon at Mid Staffordshire NHS Foundation Trust was unfit to practise because his performance was deficient.

The MPTS panel found that Raafat Gendy’s performance was not deficient and therefore that his fitness to practise was not impaired.

An assessment team …
Abortion clinics fail to meet standards
Authors: Zosia Kmietowicz
Journal: BMJ (2001)

The first national audit of abortion services in England and Wales has shown that most clinics are failing to meet at least one of the standards set out by the Royal College of Obstetricians and Gynaecologists.

The survey, which was carried just before the publication of the college's guidelines in March 2000, showed that more than a third of clinics failed to meet targets for assessing and treating women and two thirds were not offering the full range of treatment options.

The guidelines recommend …
Diuretic and natriuretic effects of long-term albumin infusion in patients with cirrhosis and ascites: a randomised controlled study
Authors: F. Vizzutti, R.G. Romanelli, V.Casini Raggi, P. Montalto, S. Pastacaldi, M. Pinzani, G. Laffi, Paolo Gentilini
Journal: Journal of Hepatology (2001)
PMO-114 Low CD39 expression marks severe regulatory t cell impairment in patients with autoimmune sclerosing cholangitis
Authors: C R Grant, R Liberal, B Holder, Y Ma, G Mieli-Vergani, D Vergani, M S Longhi
Journal: Gut (2012)

<h3>Introduction</h3> Autoimmune hepatitis (AIH)/sclerosing cholangitis overlap syndrome (autoimmune sclerosing cholangitis, AISC) is a severe hepatopathy that, in addition to the serological and histological features typical of AIH (hyper γ globulinaemia, autoantibody seropositivity and interface hepatitis), presents with bile duct abnormalities. Both conditions are associated with numerical and functional impairment of CD4<sup>+</sup>CD25<sup>high</sup> regulatory T cells (Tregs), a lymphocyte subset central to immune-tolerance. It remains unclear whether the two conditions can be distinguished on the basis of specific immune-regulatory T cell defects. To this end, we have explored a subset of Tregs expressing CD39, an ectoenzyme that contributes to Treg suppression by hydrolysing pro-inflammatory nucleotides and whose polymorphisms are associated with autoimmune disease in humans. <h3>Methods</h3> We studied 10 patients with AISC (2 females, median age: 14.5 years), 24 with AIH type 1 (12 females, median age: 16 years) and 25 healthy subjects (HS; 15 females, median age 36 years). The frequency and phenotype of circulating CD4<sup>+</sup>CD39<sup>+</sup>CD25<sup>high</sup> cells (CD39<sup>+</sup>Tregs) was assessed by flow cytometry using monoclonal antibodies to CD4, CD25, CD39, CD127 and FOXP3. The frequency of IFNγ, IL17 and TGFß-producing CD39<sup>+</sup>Tregs was determined by intracellular cytokine staining. <h3>Results</h3> The frequency of CD39<sup>+</sup>Tregs was markedly reduced in AISC (0.31±0.11) compared to AIH (4.30±0.89, p&lt;0.01) and HS (7.02±1.28, p&lt;0.01). AISC patients also had fewer CD39<sup>+</sup>FOXP3<sup>+</sup>Tregs (0.03±0.02) and CD39<sup>+</sup>CD127<sup>−</sup>Tregs (0.05±0.02) than AIH patients (FOXP3<sup>+</sup>: 0.14±0.03, p=0.05; CD127<sup>−</sup>: 0.42±0.10, p&lt;0.01) and HS (FOXP3<sup>+</sup>: 0.20±0.04, p=0.03; CD127<sup>−</sup>: 0.49±0.07, p=0.01). Analysis of cytokine profiles showed that in AISC there was a higher frequency of CD39<sup>+</sup>Tregs producing IFNγ (0.23±0.15) and IL17 (0.22±0.14) and a lower frequency of CD39<sup>+</sup>Tregs producing TGFß (0±0) than in AIH (IFNγ: 0.04±0.02, p=0.05; IL17: 0.03±0.01, p=0.03; TGFß: 0.03±0.01, p=0.09) and HS (IFNγ: 0.07±0.03 p=0.13; IL17: 0.06±0.03, p=0.11; TGFß: 0.02±0.01, p=NS). <h3>Conclusion</h3> Compared to AIH and health, CD39<sup>+</sup>Tregs in AISC are reduced in frequency and display a more proinflammatory cytokine profile. These findings suggest that immune-regulation impairment is more severe in AISC than AIH and implicate CD39 as a marker to differentiate immune-regulatory T-cell defects in the two conditions. <h3>Competing interests</h3> None declared.
The C-Word: Teenagers and Their Families Living With Cancer
Authors: Harriet S. Meyer
Journal: JAMA (1994)

"When I was ill, I desperately needed a person, or a book, that I could identify with," writes Elena Dorfman, who had rhabdomyosarcoma at age 16. Hence her creation<i>The C-Word</i>, which picks up where Jason Gaes'<i>My Book for Kids With Cansur</i>left off. Over a four-year period the author spent time with teenagers with cancer (four with acute lymphoblastic leukemia and one with osteosarcoma), their parents, siblings, and friends, photographed them, and took down their words. All respond candidly to questions like "How did you find out you had cancer?" "How did it feel when you lost your hair?" "Do you have many side effects from the chemotherapy?" "How do you feel about being the brother of someone with cancer?" "How did you feel when the cancer came back?" "What are your relationships with your parents like?" "What do you like to do with your free time when