tbuckley/cabot-search huggingface dataset:
Characterization of antigen-specific CD4+ effector T cells in vivo: immunization results in a transient population of MEL-14-, CD45RB- helper cells that secretes interleukin 2 (IL-2), IL-3, IL-4, and interferon gamma.
Authors: L M Bradley, D D Duncan, S Tonkonogy, S L Swain
Journal: The Journal of Experimental Medicine (1991)

In previous studies we demonstrated that, following activation by mitogens or alloantigens, helper T cell precursors proliferate and differentiate in vitro to produce a population of effector cells that secrete high titers of lymphokines upon restimulation. In this report, we demonstrate that a similar effector population develops in vivo following primary antigen stimulation. When restimulated with specific antigen in vitro, CD4+ T cells from mice primed 5 to 7 days previously by subcutaneous administration of keyhole limpet hemocyanin (KLH) in adjuvant, produced high levels of interleukin 2 (IL-2), IL-4, and IL-3, and little or no interferon gamma (IFN-gamma) or IL-5. The effector T cells provided excellent helper activity for in vitro antibody responses of 4-hydroxy-5-iodo-nitrophenyl acetic acid-primed B cells with the production principally of the immunoglobulin G1 (IgG1) and IgM isotypes, small quantities of IgG3, and no detectable IgG2a, or IgG2b. Antigen-specific secretion of IL-2, IL-3, and IL-4 by in vivo effectors was detectable by 12 hours following in vitro restimulation. IFN-gamma and IL-5 were not detected until 48 and 72 hours of culture, respectively, and low levels of these lymphokines were produced. Lymphokine production by primed CD4+ T cells could be induced as early as 3 days following immunization, peaked on day 5, and declined thereafter. The kinetics of in vivo appearance of effector CD4+ T cells that produce lymphokines upon restimulation in vitro were similar for each of the lymphokines examined. Mice depleted of precursor CD4+ T cells by adult thymectomy exhibited limited capacity to generate lymphokine secreting CD4+ T cells in response to primary immunization with KLH, suggesting that the majority of lymphokine producing T cells arise from short-lived and/or precursor cells. Separation of CD4+ T cells from KLH-primed mice on the basis of expression of the lymph node-specific homing receptor, MEL-14, revealed that antigen-specific production of IL-2, IL-3, IL-4, and IFN-gamma was exclusively associated with the MEL-14- subset of CD4+ T cells. Separation on the basis of CD45RB expression, demonstrated that antigen-specific lymphokine production was primarily associated with the minor CD45RB- population, which has been previously associated with memory activity. Our results indicate that primary in vivo immunization leads to the development of a transient population of helper-effectors with a unique phenotype that can produce large quantities of lymphokines and mediate excellent helper activity for B cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Treatment of Antidepressant-Associated Sexual Dysfunction With Sildenafil
Authors: H. George Nurnberg, Paula L. Hensley, Alan J. Gelenberg, Maurizio Fava, John Lauriello, Susan Paine
Journal: JAMA (2003)

Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance.To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor (SRI) antidepressants.Prospective, parallel-group, randomized, double-blind, placebo-controlled trial conducted between November 1, 2000, and January 1, 2001, at 3 US university medical centers among 90 male outpatients (mean [SD] age, 45 [8] years) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment.Patients were randomly assigned to take sildenafil (n = 45) or placebo (n = 45) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks.The primary outcome measure was score on the Clinical Global Impression-Sexual Function (CGI-SF); secondary measures were scores on the International Index of Erectile Function, Arizona Sexual Experience Scale, Massachusetts General Hospital-Sexual Functioning Questionnaire, and Hamilton Rating Scale for Depression (HAM-D).Among the 90 randomized patients, 93% (83/89) of patients treated per protocol took at least 1 dose of study drug and 85% (76/89) completed week 6 end-point assessments with last observation carried forward analyses. At a CGI-SF score of 2 or lower, 54.5% (24/44) of sildenafil compared with 4.4% (2/45) of placebo patients were much or very much improved (P<.001). Erectile function, arousal, ejaculation, orgasm, and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients. Mean depression scores remained consistent with remission (HAM-D score < or =10) in both groups for the study duration.In our study, sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants. These improvements may allow patients to maintain adherence with effective antidepressant treatment.
The importance of aerobic metabolism in the renal concentrating process
Authors: Edward Weinstein, Andrzej Manitius, Franklin H. Epstein
Journal: Journal of Clinical Investigation (1969)

The extent to which the concentrating function of the kidney depends on oxidative processes was investigated by infusing cyanide into one renal artery of dogs undergoing mild mannitol diuresis while receiving an infusion of vasopressin. This produced an abrupt fall in concentrating capacity (T(c) (H2O)) that was reversed when the cyanide infusion was stopped. The change could not be accounted for by the accompanying solute diuresis, since it was not reproduced by increasing the rate of mannitol infusion. The reduction in T(c) (H2O) induced by cyanide did not result from increased delivery of dilute urine to the collecting ducts, since free water clearance (C(H2O)), studied in other dogs during water diuresis, was unchanged or decreased by cyanide. Cyanide produced renal vasodilatation, as did intraarterial acetylcholine, but in contrast to the striking reduction in concentrating capacity evoked by cyanide, T(c) (H2O) was not significantly changed by acetylcholine. The data indicate that concentrating ability is closely tied to oxidative metabolism in the kidney, and it is suggested that the region where this is critically important is the red medulla and the thick ascending limb of Henle's loop.
Commentary: QTc dispersion may reflect vulnerability to ventricular fibrillation
Authors: R Campbell
Journal: BMJ (1996)

Peripheral vascular disease is a marker of coronary artery disease, and QT dispersion (the difference between the longest and the shortest measurable interval on the 12 lead electrocardiogram) is emerging as an important marker of serious arrhythmias and sudden death. To link these two markers is not at first intuitive, but the common ground lies in the spectre of coronary artery disease. Darbar et al correlate peripheral vascular disease not just with any coronary artery disease but with the type that carries the highest risk of death. With a modest patient cohort (49) cardiac death was strongly correlated with the QTc dispersion. Values of > 60 ms had a 92% sensitivity and an 81% specificity in …
Reduced Serum Testosterone and Prolactin Levels in Male Distance Runners
Authors: Garry D. Wheeler
Journal: JAMA (1984)

To investigate whether endurance running in men produced basal hormonal changes similar to those reported in women, we obtained blood samples from 31 men running at least 64 km each week and 18 sedentary controls for measurement of levels of total testosterone, non-sex hormone-binding globulin-bound and free testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and cortisol. The mean levels of total and nonspecifically bound testosterone as well as prolactin were significantly lower than in controls, although levels remained within the physiological range. Other hormone levels were similar in both groups. The lowered testosterone and prolactin levels parallel the changes reported in women runners. (<i>JAMA</i>1984;252:514-516)
Pseudohypoparathyroidism (PHP)—A Disease of the Second Messenger 3′5′-CyCHc AMP.
Authors: Sigmund R. Greenberg, Sheldon I. Karabell, G.A. Saade
Journal: Annals of Internal Medicine (1970)

Meeting Abstracts1 May 1970Pseudohypoparathyroidism (PHP)—A Disease of the Second Messenger 3′5′-CyCHc AMP.Sigmund R. Greenberg, M.D., F.A.C.P., Sheldon I. Karabell, M.D., G.A. Saade, M.D.Sigmund R. Greenberg, M.D., F.A.C.P.Search for more papers by this author, Sheldon I. Karabell, M.D.Search for more papers by this author, G.A. Saade, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-787_5 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince hormonal information is transferred to the cell by the adenyl cyclase system with the production of 3′5′-cyclic adenosine monophosphate (AMP) (second messenger), end organ refractoriness in pseudohypoparathyroidism (PHP) can be demonstrated by a decreased 3′5′-cyclic AMP renal excretion after parathormone (PTH). Two sisters (11 and 8 years of age) were discovered to have PHP. J.D. (11 years) was admitted because of progressive extra-pyramidal signs, punctate calcification of the basal ganglia, short stature, Turner syndrome appearance, strabismus, absence of the fourth and fifth knuckles, hypocalcemia, and asthma. Her sister, R.A.D., (8 years) revealed somatic changes without symptoms. Both patients had... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 787-788KeywordsAdenosine monophosphateAsthmaExcretionGangliaHypocalcemiaInformation technologyParathyroid hormonePseudohypoparathyroidismTurner syndrome Issue Published: 1 May 1970 PDF downloadLoading ...
Susceptibility to Exacerbation in Chronic Obstructive Pulmonary Disease
Authors: John R. Hurst, Jørgen Vestbo, Antonio Anzueto, Nicholas Locantore, Hana Müllerova, Ruth Tal-Singer, Bruce Miller, David A. Lomas, Alvar Agusti, William MacNee, Peter Calverley, Stephen Rennard, Emiel F.M. Wouters, Jadwiga A. Wedzicha
Journal: New England Journal of Medicine (2010)

Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity.We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years.Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count.Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
A Twentieth-Century Surgeon: My Life in the Massachusetts General Hospital
Authors: B. Eiseman
Journal: JAMA (1993)

Most such autobiographies are uninspiring, which raises a problem for their reviewers, options being insult or perjury. But the reflections of America's senior surgical statesman, Claude Welch of Boston, fortunately are an exception to this rule. As an active player in so many aspects of the changing scene during a half century of medical practice, Welch turns his memoirs into a history, to which he adds his personal observations. "Welch somehow found time both to be a busy practitioner and to participate as a leader in almost every organization that influenced the changes in medical practice..." As is the case with so many "Boston surgeons," Claude Welch was born and raised
G6PD deficiency, absence of α-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia
Authors: Françoise Bernaudin, Suzanne Verlhac, Sylvie Chevret, Martine Torres, Lena Coic, Cécile Arnaud, Annie Kamdem, Isabelle Hau, Maria Grazia Neonato, Christophe Delacourt
Journal: Blood (2008)
Activity and impact on antibiotic use and costs of a dedicated infectious diseases consultant on a septic orthopaedic unit
Authors: Ilker Uçkay, Nathalie Vernaz-Hegi, Stephan Harbarth, Richard Stern, Laurence Legout, Laetitia Vauthey, Tristan Ferry, Anne Lübbeke, Mathieu Assal, Daniel Lew, Pierre Hoffmeyer, Louis Bernard
Journal: Journal of Infection (2009)
ASSOCIATION OF CYP2C19*2 TO ALTERED CLOPIDOGREL REACTIVITY AS MEASURED BY A POINT-OF-CARE ANALYSIS
Authors: Derek Yiu Fai So, Irena Szymanska, Alex Stewart, Michel Le May, Marino Labinaz, Sandro Goncalves, Olivia Assogba, Chris Glover, Sonny Dandona, Robert Roberts
Journal: Journal of the American College of Cardiology (2010)
Super-macroporous poly(ethoxytriethyleneglycol acrylate) hydrogels for sustained delivery of hydrophilic drugs
Authors: Petar Petrov, Denitsa Momekova, Bistra Kostova, Georgi Momekov, Natalia Toncheva-Moncheva, Christo B. Tsvetanov, Nikolay Lambov
Journal: Journal of Controlled Release (2010)
North of England evidence based guideline development project: summary guideline for non-steroidal anti-inflammatory drugs versus basic analgesia in treating the pain of degenerative arthritis
Authors: M. Eccles, N. Freemantle, J. Mason
Journal: BMJ (1998)

Other members of the guideline development and project groups are listed in the Appendix This guideline addresses the appropriate use of non-steroidal anti-inflammatory drugs in the primary care treatment of patients with joint pain believed to be caused by degenerative arthritis. It does not consider therapies other than drug treatment. General practitioners must use their professional knowledge and judgement when applying guideline recommendations to the management of individual patients. They should note the information, contraindications, interactions, and side effects contained in the British National Formulary.1 This is a summary of the full version of the guideline.2 In this article, the statements accompanied by categories of evidence (cited as Ia, Ib, IIa, IIb, III, and IV) and recommendations classified according to their strength (A, B, C, or D) are as described previously and are summarised in the box.3 ### Summary points The methods used to develop the guideline have been described previously.3Briefly, we searched the electronic databases Medline and Embase, using a combination of subject heading and free text terms aimed at locating systematic reviews, meta-analyses, randomised trials, quality of life studies, and economic studies. The search was backed up by the expert knowledge and experience of group members. ### Strength of recommendation
Children as consumers
Authors: C. Hart, R. Chesson
Journal: BMJ (1998)

Children are important users of health services, accounting for up to a quarter of general practitioner consultations1 and 30% of the workload in accident and emergency departments.2 However, their needs are given insufficient priority by policy makers and health service professionals. Last year a report of the British government's health committee stressed that a change in attitude was needed and that it was important to listen to children and to take their views into account.3

Although consumers have an important role in reforming health care,4 the paternalistic attitude still prevailing among health professionals when it comes to consumer involvement in health care and research can make this difficult.5 Patient passivity begins early in life6 so we should not be surprised that adult users acquiesce. In this article we discuss why children should be consulted directly, how this is to be achieved, and finally what may be required to bring about change.

#### Summary points

Children are major users of health services but are rarely consulted as healthcare consumers

Although parents are extensively used as proxies for children, their accounts may not always accurately reflect children's perceptions

Large numbers of children are cared for and treated by staff who have no paediatric training and abilities to communicate cannot be assumed

Children's concepts of hospital care and illness differ greatly from those of adults

Children may be able to express their opinions if they are sought using appropriate methods

Staff need to be trained to enable the child's voice to be heard and may need to consult colleagues in departments of child and family psychiatry and clinical psychology and develop closer contacts with teachers and social workers

### Parent as proxy

In Britain, although there has been an increasing emphasis on obtaining the views of health service users, children are rarely included. This …
Possible risk of endometriosis for Seveso, Italy, residents: an assessment of exposure to dioxin.
Authors: F Y Bois, B Eskenazi
Journal: Environmental Health Perspectives (1994)

A recent study by Rier et al. showed that rhesus monkeys exposed daily for 4 years to 5 or 25 ppt of dioxin in food develop endometriosis, with incidence and severity related to dose. We aimed to determine whether the total time-integrated dioxin exposure of a human population could be comparable to that of Rier's monkeys. We selected a sample of residents of Seveso, Italy, who were acutely exposed to high levels of dioxin following an accident in 1976. We conducted a toxicokinetic analysis which takes into account species and exposure differences in dose and timing between humans and monkeys. The area under the time-concentration curve for dioxin in fat, which corresponds to cumulative exposure over time, ranges for some of the most heavily exposed Seveso residents from approximately 1.7 x 10(6) ppt-days to 1.1 x 10(8) ppt-days. These values exceed in all cases the values for the monkeys exposed to 25 ppt or 5 ppt. Given their exposure, the Seveso population should be an ideal epidemiologic cohort to rule out or confirm whether exposure to dioxin leads to an increased risk of endometriosis in humans.
A SIMPLE METHOD OF FINDING AN EASILY ACCESSIBLE PORTION OF THE LATERAL SINUS.
Authors: EMIL AMBERG
Journal: JAMA (1906)

Four right and four left temporal bones picked out at random, show that an easily accessible portion of the lateral sinus can be found when we open that part of the mastoid process which is located (Fig. 1) in the direction of the line which divides into two halves the angle formed by the linea temporalis and the anterior border of the mastoid process (an angle of about 115 degrees). This topographic consideration is important from a clinical point of view.
Letter: Laparoscopic tubal ligation.
Authors: K R Greene, D I Wise, H A Melville
Journal: BMJ (1974)

Control programme referred to in Dr. Payne's letter the performance of the U.C.H. laboratory was equally satisfactory -that is, calcium, mean bias 0 00 and precision (S.D.) 0-08 mg/ 100 ml; albumin, mean bias 0-15 and precision (S.D.) 0-12 g/100 ml.In our opinion an important reason for the discrepancy lies in the manner in which the reference albumin level has been selected.Dr. Payne and his colleagues, while stating that their normal range for serum albumin is 3 7-4 7 g/ 100 ml, chose to use 4 0 g/100 ml as their reference point because it gave a mean adjusted calcium level of 9 7 mg/100 ml.At U.C.H. 4-6 g/100 ml was chosen as the reference level because it approximated to the mean ooncentration found in a balanced population of 1,000 healthy blood donors, with equal numbers of males and females in 10 age groups between 18 and 65 years.Whatever albumin level is chosen as the point of reference is arbitrary because there are significant differences in the levels between the sexes, and very appreciable changes occur with ageing and alteration of posture.Thus while our normal range for plasma albumin in male outpatients of 18-25 years is 4-4-5 3 g/ 100 ml the 95% limits applicable to female inpatients of 56-65 years is 3 6-4-5 g/100 ml.Fortunately the regression coefficients of total plasma calcium on albumin arrived at by Dr. Payne's team and at U.C.H. are very close to one another and therefore there is no reason why Mr.
Managed Care and Quality
Authors: Bruce C. Vladeck
Journal: JAMA (1995)

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