tbuckley/cabot-search huggingface dataset:
Myelotoxicity of D-penicillamine.
Authors: A G Kay
Journal: Annals of the Rheumatic Diseases (1979)

Information has been collected on 10 patients, 9 with marrow depression and 1 in whom the diagnosis was presumed. Six of the 10 patients died. The sequentially recorded blood counts on at least 5 of the patients showed a downward trend of the white cell and platelet counts while D-penicillamine was still being administered. One patient suddenly developed leucopenia and thrombocytopenia with a streptococcal septicaemia.
The Phosphotyrosine Phosphatase SHP-2 Participates in a Multimeric Signaling Complex and Regulates T Cell Receptor (TCR) coupling to the Ras/Mitogen-activated Protein Kinase (MAPK) Pathway in Jurkat T Cells
Authors: Julie A. Frearson, Denis R. Alexander
Journal: The Journal of Experimental Medicine (1998)

Src homology 2 (SH2) domain–containing phosphotyrosine phosphatases (SHPs) are increasingly being shown to play critical roles in protein tyrosine kinase–mediated signaling pathways. The role of SHP-1 as a negative regulator of T cell receptor (TCR) signaling has been established. To further explore the function of the other member of this family, SHP-2, in TCR-mediated events, a catalytically inactive mutant SHP-2 was expressed under an inducible promoter in Jurkat T cells. Expression of the mutant phosphatase significantly inhibited TCR-induced activation of the extracellular-regulated kinase (ERK)-2 member of the mitogen-activated protein kinase (MAPK) family, but had no effect on TCR-ζ chain tyrosine phosphorylation or TCR-elicited Ca2+ transients. Inactive SHP-2 was targeted to membranes resulting in the selective increase in tyrosine phosphorylation of three membrane-associated candidate SHP-2 substrates of 110 kD, 55-60 kD, and 36 kD, respectively. Analysis of immunoprecipitates containing inactive SHP-2 also indicated that the 110-kD and 36-kD Grb-2–associated proteins were putative substrates for SHP-2. TCR-stimulation of Jurkat T cells expressing wild-type SHP-2 resulted in the formation of a multimeric cytosolic complex composed of SHP-2, Grb-2, phosphatidylinositol (PI) 3′-kinase, and p110. A significant proportion of this complex was shown to be membrane associated, presumably as a result of translocation from the cytosol. Catalytically inactive SHP-2, rather than the wild-type PTPase, was preferentially localized in complex with Grb-2 and the p85 subunit of PI 3′-kinase, suggesting that the dephosphorylating actions of SHP-2 may regulate the association of these signaling molecules to the p110 complex. Our results show that SHP-2 plays a critical role in linking the TCR to the Ras/MAPK pathway in Jurkat T cells, and also provide some insight into the molecular interactions of SHP-2 that form the basis of this signal transduction process.
The spandrel may be related to culture not brain function
Authors: Andrew N. Iwaniuk, Ian Q. Whishaw
Journal: Behavioral and Brain Sciences (2001)

Finlay et al. describe a method of examining brain evolution, but it has limits that may hinder extrapolation to all vertebrate taxa or the understanding of how brains work. For example, members of different orders have brain and behavioral organization that are fundamentally different. Future investigations should incorporate a phylogenetic approach and more attention to behavior to further test their conclusions.
Does Natalizumab Therapy Benefit Patients With Multiple Sclerosis?
Authors: Olaf Stüve, Gary R. Cutter
Journal: JAMA Neurology (2014)

Doesnatalizumabtherapybenefitpatientswithmultiplesclerosis (MS)?Theobviousanswer isyes.Natalizumabwasapprovedfor patientswithrelapsingformsofMSbyregulatoryagenciesbased on the results of 2phase3 clinical trials that showedsubstantial benefitswithregardtoclinicalandparaclinicaloutcomes.1,2Post hocanalysessuggestthatmanywhoadheretonatalizumabtherapyhaveahigh likelihoodofbeingdisease free formanyyears.3 Basedontheseefficacydata,patientsshouldperhapsbetreated withnatalizumab indefinitelyoruntil theyseemtohave transitioned to secondary progressiveMS. However, shortly after its initial approval, itwasdeterminedthatnatalizumabuse isassociatedwithprogressivemultifocalencephalopathy(PML),anopportunistic infectionofthecentralnervoussystemthat iscaused by the humanpolyomavirus JohnCunninghamvirus (JCV). It isunclearwhynatalizumab increases the riskofPML,but itsmechanismofantagonizingα4 integrin–mediatedcellmigration likelydiminishes immunesurveillanceof thebrainandspinalcord.Whiledebatablylow,thisriskiscauseforconcernamong physiciansandatvarious times for somepatientsbasedontheir risktolerance.Almostsince its approval, attemptshavebeen made to determine whether discontinuationofnatalizumabissafe, inwhomtheagentshould bediscontinued,andhow.Althoughthepathogenicevents leading tonatalizumab-associatedPML remain opaque, the following3 factorsareassociatedwith theoverall riskof this infection: apositiveserostatusforanti–JCVantibodies, theutilizationof immunosuppressantsbeforeinitiatingnatalizumabuse,andthedurationofnatalizumabtherapy (aloneor incombination).4 If all 3 risk factorsarepresent, the riskofnatalizumab-associatedPML is approximately 1 in 90,which seemsunacceptably high given that PML is associatedwith ahighmorbidity andmortality and that alternative therapiesexist.Thedevelopmentof anassay to identifypatientswhoarepositive for JCVandthe identification of theotherknownrisk factors representamajorplus for initiating therapy, butwhenapatient becomespositive for JCVorhas beenonanatalizumabregimenforasubstantial amountof time anddesires to stop therapy, the path is less clear. Consequently,neurologistshavebeen investigatinghowto transition patients who want to cease natalizumab to other therapies.5,6Thegoalofa treatmentchange is2-fold,namely, to lowertheriskofPMLandtopreventMSdiseasereactivation.The riskofPMListhoughttobeabsentornegligibleforanyoftheother approvedtherapies,whereas it remainselevatedat least foraperiodafternatalizumab isdiscontinued.7Theriskofdisease reactivation is high, and it occurswithin 3 to 6months after the last natalizumabdose is administered.8 Related article page 954 Figure. PatientsWithMultiple Sclerosis Experience aMeaningful Reduction in Disease Activity During Natalizumab Therapy
Jogging and Health
Authors: Thomas J. Bassler
Journal: JAMA (1975)

<h3>To the Editor.—</h3> We agree with the COMMENTARY by Wynder and Peacock (229:1743, 1974) that disease prevention will become the first line of offense in tomorrow's medical care. Through the American Medical Joggers Association (AMJA), we advocate the vigorous exercise and teetotaling life-style of the Olympic marathon runner for everyone, because immunity to coronary heart disease appears to coexist with the ability to cover 42 km on foot. This has been reported in the Masai warriors (<i>N Engl J Med</i>284:694, 1971) and the Tarahumara Indians (<i>Am Heart J</i>81:304, 1971). We postulate that it is also true of marathon runners, even though they may have some of the risk factors peculiar to our Western civilization (<i>Science</i>183:256, 1974). We are encouraged by the article by Kavanagh et al (229:1602, 1974) that showed that the marathon runner's life-style is suitable for some cardiac patients after they have recovered from myocardial
The Sky Is Falling?
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1974)

The Sky Is Falling?One of the realities that the biomedical research enterprise must now face in dealing with its principal patron, the federal government, is that on the subject of adequacy of financial support, the credibility of the scientific leadership has been considerably frayed by constant reiteration of doomsday prophecies.There should be no doubt, of course, that, in recent years, abrupt starts and stops in government programs have caused serious problems for medical schools and associated research institutions. And, in consequence, the administrators of these institutions have taken the path of exercising their right to petition for relief. . . .
Personality Disorder Reviewed
Authors: F J Dunne
Journal: BMJ (1994)

Psychiatry has been rather poor at defining its own terms, and personality disorders particularly have suffered in this regard. Some personality types described represent little more than the personal opinions of psychiatrists. The overlap between several disorders leads to confusion, and it is not surprising that it proves difficult or impossible to subdivide people into discrete categories. Some findings are consistent and suggest that there is an excess of personality disorder among men, a decreasing rate with increasing age, …
Activation of Cl secretion during chemical hypoxia by endogenous release of adenosine in intestinal epithelial monolayers.
Authors: J B Matthews, K J Tally, J A Smith, A J Zeind, B J Hrnjez
Journal: Journal of Clinical Investigation (1995)

Intestinal ischemia is characterized by rapid early inhibition of absorptive function and the appearance of net secretion, although why active secretion persists in the setting of a mucosal energy deficit is unknown. The cryptlike epithelial line T84, a well-characterized model of intestinal Cl- secretion, develops a prominent increase in short-circuit current (Isc, indicative of active Cl- transport) in response to "hypoxia" induced by metabolic inhibitors. The increased Isc is associated with the initial decrease in monolayer ATP content. The Isc is transient and disappears with progressive energy depletion, although graded degrees of ATP depletion induce a more sustained Isc response. Chromatographic analysis and secretory bioassays show that the Isc response to metabolic inhibitors is related to the endogenous release of adenosine into the extracellular space in quantities sufficient to interact locally with stimulatory adenosine receptors. Unlike its classical role as a metabolic feedback inhibitor, adenosine appears to function as an autocrine "feed-forward" activator of active intestinal Cl- secretion. These studies suggest a novel role for adenosine in the conversion of the gut from an absorptive to a secretory organ during ischemic stress, thus contributing to the initial diarrheal manifestation of intestinal ischemia.
Amebic Granuloma
Authors: Charles G. Spicknall, E. Converse Peirce
Journal: New England Journal of Medicine (1954)

REPORTS of cases of amebic granuloma are rare in the North American literature, and no complete review has been published in journals of the United States. At this hospital, in the last five years, we have seen 4 cases among 214 patients with amebic colitis. It is probable that the lesion is not a rare complication of amebiasis, and since the incidence of amebiasis in the United States has been found to be 1.7 to 25.9 per cent,1 according to the area surveyed, there must be many cases that are not recognized. When these patients are adequately treated with antiamebic . . .
Detection of relevant amounts of cow's milk protein in non‐pre‐packed bakery products sold as cow's milk‐free
Authors: V. Trendelenburg, N. Enzian, J. Bellach, S. Schnadt, B. Niggemann, K. Beyer
Journal: Allergy (2015)

Currently, there is no mandatory labelling of allergens for non-pre-packed foods in the EU. Therefore, consumers with food allergy rely on voluntary information provided by the staff. The aim of this study was to characterize allergic reactions to non-pre-packed foods and to investigate whether staff in bakery shops were able to give advice regarding a safe product choice.Questionnaires were sent to 200 parents of children with a food allergy. Staff of 50 bakery shops were interviewed regarding selling non-pre-packed foods to food-allergic customers. Bakery products being recommended as 'cow's milk-free' were bought, and cow's milk protein levels were measured using ELISA.A total of 104 of 200 questionnaires were returned. 25% of the children experienced an allergic reaction due to a non-pre-packed food from bakery shops and 20% from ice cream parlours. Sixty percent of the bakery staff reported serving food-allergic customers at least once a month, 24% once a week. Eighty four percent of the staff felt able to advise food-allergic consumers regarding a safe product choice. Seventy three 'cow's milk-free' products were sold in 44 bakery shops. Cow's milk could be detected in 43% of the bakery products, 21% contained >3 mg cow's milk protein per serving.Staff in bakery shops felt confident about advising customers with food allergy. However, cow's milk was detectable in almost half of bakery products being sold as 'cow's milk-free'. Every fifth product contained quantities of cow's milk exceeding an amount where approximately 10% of cow's milk-allergic children will show clinical relevant symptoms.
Association of Blood Transfusion With Increased Mortality in Myocardial Infarction
Authors: Saurav Chatterjee, Jørn Wetterslev, Abhishek Sharma, Edgar Lichstein, Debabrata Mukherjee
Journal: JAMA Internal Medicine (2012)

<h3>Background</h3>The benefit of blood transfusion in patients with myocardial infarction is controversial, and a possibility of harm exists.<h3>Methods</h3>A systematic search of studies published between January 1, 1966, and March 31, 2012, was conducted using MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. English-language studies comparing blood transfusion with no blood transfusion or a liberal vs restricted blood transfusion strategy were identified. Two study authors independently reviewed 729 originally identified titles and abstracts and selected 10 for analysis. Study title, follow-up period, blood transfusion strategy, and mortality outcomes were extracted manually from all selected studies, and the quality of each study was assessed using the strengthening Meta-analysis of Observational Studies in Epidemiology checklist.<h3>Results</h3>Studies of blood transfusion strategy in anemia associated with myocardial infarction were abstracted, as well as all-cause mortality rates at the longest available follow-up periods for the individual studies. Pooled effect estimates were calculated with random-effects models. Analyses of blood transfusion in myocardial infarction revealed increased all-cause mortality associated with a strategy of blood transfusion vs no blood transfusion during myocardial infarction (18.2% vs 10.2%) (risk ratio, 2.91; 95% CI, 2.46-3.44; P &lt; .001), with a weighted absolute risk increase of 12% and a number needed to harm of 8 (95% CI, 6-17). Multivariate meta-regression revealed that blood transfusion was associated with a higher risk for mortality independent of baseline hemoglobin level, nadir hemoglobin level, and change in hemoglobin level during the hospital stay. Blood transfusion was also significantly associated with a higher risk for subsequent myocardial infarction (risk ratio, 2.04; 95% CI, 1.06-3.93; P = .03).<h3>Conclusions</h3>Blood transfusion or a liberal blood transfusion strategy compared with no blood transfusion or a restricted blood transfusion strategy is associated with higher all-cause mortality rates. A practice of routine or liberal blood transfusion in myocardial infarction should not be encouraged but requires investigation in a large trial with low risk for bias.
Age-Related Macular Degeneration Is the Leading Cause of Blindness . . .
Authors: Neil M. Bressler
Journal: JAMA (2004)

ObjectiveTo estimate the prevalence and distribution of age-related macular degeneration (AMD) in the United States by age, race/ethnicity, and gender.MethodsSummary prevalence estimates of drusen 125 µm or larger, neovascular AMD, and geographic atrophy were prepared separately for black and white persons in 5-year age intervals starting at 40 years. The estimated rates were based on a meta-analysis of recent population-based studies in the United States, Australia, and Europe. These rates were applied to 2000 US Census data and to projected US population figures for 2020 to estimate the number of the US population with drusen and AMD.ResultsThe overall prevalence of neovascular AMD and/or geographic atrophy in the US population 40 years and older is estimated to be 1.47% (95% confidence interval,1.38%-1.55%), with 1.75 million citizens having AMD. The prevalence of AMD increased dramatically with age, with more than 15% of the white women older than 80 years having neovascular AMD and/or geographic atrophy. More than 7 million individuals had drusen measuring 125 µm or larger and were, therefore, at substantial risk of developing AMD. Owing to the rapidly aging population, the number of persons having AMD will increase by 50% to 2.95 million in 2020. Age-related macular degeneration was far more prevalent among white than among black persons.ConclusionAge-related macular degeneration affects more than 1.75 million individuals in the United States. Owing to the rapid aging of the US population, this number will increase to almost 3 million by 2020.
Reliability of symptoms to determine use of bone scans to identify bone metastases in lung cancer: prospective study
Authors: Martin Hetzel, Juergen Hetzel, Coskun Arslandemir, Karin Nüssle, Holger Schirrmeister
Journal: BMJ (2004)

Based on the hypotheses that most skeletal metastases in lung cancer are clinically symptomatic, that the incidence of bony metastases in early stages is low, and that bone scintigraphy has a sensitivity of nearly 100%, leading professional societies recommend diagnostic skeletal imaging depending on clinical symptoms. 1 2No study has assessed the significance of skeletal symptoms as a criterion for skeletal imaging in patients with lung cancer since 1991. 3 But in the intervening period gamma camera technology has been considerably refined and more sensitive methods such as magnetic resonance imaging have become available for skeletal imaging.We redetermine the role of symptoms and serum concentrations in detecting bony metastases in lung cancer and reassess the accuracy of bone scans for screening.
IMPACT OF VASCULAR FUNCTION ON PLATELET ACTIVATION IN PATIENTS AFTER PERCUTANEOUS CORONARY INTERVENTION
Authors: Gerasimos Siasos, Dimitris Tousoulis, Stamatios Kioufis, Evangelos Oikonomou, Marina Zaromitidou, Konstantinos Maniatis, Eleni Kokkou, Savvas Mazaris, Theodosia Konsola, Manolis Vavuranakis, Nikolaos Papageorgiou, Panagiotis Tourikis, Christina Kollia, Christodoulos I Stefanadis
Journal: Journal of the American College of Cardiology (2014)
SENSITIVITY OF PNEUMOCOCCI TO SULFAPYRIDINE: A RAPID QUALITATIVE TEST FOR RESISTANCE; CLINICAL EVALUATION OF THE PROBLEM
Authors: Frederick J. Moore
Journal: JAMA (1941)

Differences in the sensitivity of pneumococci to sulfapyridine have been suggested since the earliest days of its use. 1 MacLean, Rogers and Fleming 2 observed decided differences both in vivo and in vitro, and developed, as did Macleod and Daddi, 3 a strain resistant to sulfapyridine by passage of a sensitive strain through treated mice. These observations have been confirmed and extended 4 and may be summarized as follows: Pneumococci differ profoundly in their sensitivity to the sulfonamides; resistant strains occur in nature; sensitive strains may become resistant when they are exposed to the drug in either the test tube, mouse or human being; resistant strains are probably permanently resistant.  The clinical implications of these results are most grave. The rational therapy of pneumococcic pneumonia demands knowledge of the sensitivity or resistance of the organism: chemotherapy in the absence of this knowledge is analogous to serotherapy in the absence of
Eyestrain as a Cause of Headache and Other Nervous Symptoms—A Question of Precedence.
Authors: Geo. M. Gould
Journal: JAMA (1904)

Philadelphia, March 12, 1904. <h3>To the Editor:</h3> —Concerning the courteous note of Dr. A. L. Ranney, under the above heading inThe JournalMarch 12, kindly permit me a few words of reply. I am conversant with the literature to which Dr. Ranney points, and it has always given me pleasure to emphasize the discoveries in medical science made by Americans. To Dr. Stevens and to Dr. Ranney credit is due for the first, continuous and indefatigable advocacy of the rôle of heterophoria in causing eyestrain and its reflexes. But my contention is a very different one. I believe that heterophoria has no influence or but little in causing eyestrain or the reflex ocular neuroses under discussion. In my writings, I have persistently advocated the view that tenotomy is not only unnecessary, but is really a prevention of cure. To me heterophoria is one of the results of eyestrain, and
Surgical Correction of Mitral Regurgitation in the Elderly
Authors: Delphine Detaint, Thoralf M. Sundt, Vuyisile T. Nkomo, Christopher G. Scott, A. Jamil Tajik, Hartzell V. Schaff, Maurice Enriquez-Sarano
Journal: Circulation (2006)

In the elderly, mitral regurgitation (MR) is frequent, but surgery risks are considered high. Benefits and indications of MR surgery are uncertain in the elderly.Baseline characteristics, outcome, and trends for surgical results improvement were analyzed in elderly patients (> or = 75 years of age; n=284) operated on for MR in 1980 to 1995 compared with younger patients (65 to 74 years of age, n=504; and <65 years of age, n=556). Preoperatively, class III to IV symptoms, atrial fibrillation, coronary disease, creatinine, and comorbidity index were more severe in elderly patients (all P<0.002). In the long term after surgery, observed survival stratified by age (> or = 75, 65 to 74, <65 years) was lower in elderly than in younger patients (at 5 years, 57+/-3%, 73+/-2%, and 85+/-2%, respectively; P<0.001), but ratios of observed to expected survival were similar (83%, 85%, and 88%, respectively). In multivariate analysis adjusted to expected survival, elderly patients showed no difference in life expectancy restoration compared with younger patients (adjusted hazard ratio, 0.89; 95% confidence interval, 0.73 to 1.30; P=0.54). Temporal trends showed that risk of operative mortality, although higher in elderly patients (P<0.001), declined markedly for all ages (27% to 5% in those > or = 75 years of age, P<0.01; 21% to 4% in those 65 to 74 years of age, P<0.01; and 7% to 2% in those <65 years of age, P=0.06), with a parallel decline in low cardiac output and length of hospital stay. Over time, valve repair feasibility increased in all age groups (30% to 84% overall and 31% to 93% in degenerative MR; P<0.0001).Elderly patients undergoing MR surgery display more severe preoperative characteristics and incur higher operative risks than younger patients. However, restoration of life expectancy after surgery is similar in elderly and younger patients, and outstanding recent surgical improvements particularly benefited elderly patients. Thus, elderly patients with MR can now carefully be considered for surgery before refractory heart failure is present.