tbuckley/cabot-search huggingface dataset:
In vitro insulin secretion by pancreatic tissue from infants with diazoxide-resistant congenital hyperinsulinism deviates from model predictions
Authors: Jean-Claude Henquin, Myriam Nenquin, Christine Sempoux, Yves Guiot, Christine Bellanné-Chantelot, Timo Otonkoski, Pascale de Lonlay, Claire Nihoul-Fékété, Jacques Rahier
Journal: Journal of Clinical Investigation (2011)

Congenital hyperinsulinism (CHI) is the major cause of persistent neonatal hypoglycemia. CHI most often occurs due to mutations in the ABCC8 (which encodes sulfonylurea receptor 1) or KCNJ11 (which encodes the potassium channel Kir6.2) gene, which result in a lack of functional KATP channels in pancreatic β cells. Diffuse forms of CHI (DiCHI), in which all β cells are abnormal, often require subtotal pancreatectomy, whereas focal forms (FoCHI), which are characterized by localized hyperplasia of abnormal β cells, can be cured by resection of the lesion. Here, we characterized the in vitro kinetics of insulin secretion by pancreatic fragments from 6 DiCHI patients and by focal lesion and normal adjacent pancreas from 18 FoCHI patients. Responses of normal pancreas were similar to those reported for islets from adult organ donors. Compared with normal pancreas, basal insulin secretion was elevated in both FoCHI and DiCHI tissue. Affected tissues were heterogeneous in their secretory responses, with increased glucose levels often producing a rapid increase in insulin secretion that could be followed by a paradoxical decrease below prestimulatory levels. The KATP channel blocker tolbutamide was consistently ineffective in stimulating insulin secretion; conversely, the KATP channel activator diazoxide often caused an unanticipated increase in insulin secretion. These observed alterations in secretory behavior were similar in focal lesion and DiCHI tissue, and independent of the specific mutation in ABCC8 or KCNJ11. They cannot be explained by classic models of β cell function. Our results provide insight into the excessive and sometimes paradoxical changes in insulin secretion observed in CHI patients with inactivating mutations of KATP channels.
Advance directives: questionnaire survey of NHS trusts
Authors: P. Diggory
Journal: BMJ (2000)

An advance directive gives patients the legal right to give or withhold consent to specific medical treatments prospectively. This provides them with some reassurance about the dying process being managed in accordance with their wishes. Apprehension could be further allayed if it were known that the legal status of advance directives was consistently applied across the NHS.

Guidance on advance statements about medical treatment was initially published by the BMA in 1995.1 The legally binding status of advance directives was reiterated by Luttrell in 1996.2 Nevertheless, in 1998 a survey of 214 general practitioners found that only 49% were aware that advance directives carry legal force.3 In 1999 the NHS Executive issued guidance on withholding consent to treatment4 and the General Medical Council issued guidance on the current legal position on advance directives.5 It remains unclear how NHS trusts have responded to this guidance and to …
Production of a B cell growth-promoting activity, (DL)BCGF, from a cloned T cell line and its assay on the BCL1 B cell tumor.
Authors: S L Swain, R W Dutton
Journal: The Journal of Experimental Medicine (1982)

Culture supernatants from a long-term alloreactive T cell line, the Dennert line C.C3.11.75 (DL) contain a B cell-growth-promoting activity. This activity can be assayed on normal B cells or on the in vivo BCL1 tumor line. We have called this activity (DL)BCGF. This activity can be distinguished from the T cell-replacing factor activity we had earlier found in DL supernates [(DL)TRF], which is required together with IL2 for the B cell plaque-forming cell response to erythrocyte antigens. The (DL)BCGF can be absorbed on untreated or glutaraldehyde-fixed BCL1. This absorption does not remove (DL)TRF activity. The production of (DL)BCGF is greatly enhanced when DL is cultured with IL2-containing supernatants. Sublines or clones of DL (DL.B10 and DL.A4) have been obtained that make large amounts of (DL)BCGF in the absence of any stimulator cells or IL2. B cells from the Xid-deficient male (DBA/2 X CBA/N)F1 mice do not respond to (DL)BCGF.
Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease
Authors: Bryan N. Becker, Peter C. Brazy, Yolanda T. Becker, Jon S. Odorico, Thomas J. Pintar, Bradley H. Collins, John D. Pirsch, Glen E. Leverson, Dennis M. Heisey, Hans W. Sollinger
Journal: Kidney International (2000)
Effects of Cool, Dry Air Stimulation on Peripheral Lung Mechanics in Asthma
Authors: DAVID A. KAMINSKY, JASON H. T. BATES, CHARLES G. IRVIN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We have previously demonstrated that peripheral airway resistance (Rp) rises more in asthmatics than in nonasthmatic control subjects after segmental challenge with cool, dry air. To better understand this rise in Rp, we used a stop-flow method to measure the decay of segment pressure with time that yielded information on airway resistance (Raw), final plateau pressure (Pp), and peripheral lung compliance (Cp). After stop-flow maneuvers in all seven asthmatics and all seven normal subjects, pressure decayed smoothly without an initial sudden drop. This finding suggests that Raw was negligible and that the predominant site of flow resistance was the collateral pathways of the obstructed segment. Asthmatics had a significantly higher Pp and lower Cp at baseline than did normal subjects, but neither Pp nor Cp changed after challenge. Pp and Rp were significantly correlated. When interpreted in terms of a single-compartment nonlinear model, we concluded that Rp is predominantly determined by the resistance of the collateral airways rather than the more proximal airways. We also concluded that, compared with normal subjects, asthmatics have (1) more collateral airway narrowing and closure and lower segmental compliance, and (2) after challenge, increased collateral airway narrowing or closure without a change in compliance of the distal lung parenchyma. These results reflect the fundamental differences in peripheral lung mechanics between asthmatic and nonasthmatic subjects and in their response to directly instilled cool, dry air.
Significance of a negative exercise thallium test in the presence of a critical residual stenosis after thrombolysis for acute myocardial infarction.
Authors: J M Sutton, E J Topol
Journal: Circulation (1991)

BACKGROUND After thrombolytic therapy for acute myocardial infarction, increasing emphasis is placed on early submaximal exercise testing, with further intervention advocated only for demonstrable ischemia. Although significant residual coronary artery lesions after successful thrombolysis are common, many patients paradoxically have no corresponding provokable ischemia. METHODS AND RESULTS The relation between significant postthrombolytic residual coronary artery disease and a negative early, submaximal exercise thallium-201 tomogram was studied among 101 consecutive patients with uncomplicated myocardial infarction and at least 70% residual stenosis of the infarct artery. A negative test occurred in 49 (48.5%) patients with a mean 88% residual infarct artery stenosis. Further characteristics of the group were as follows: mean time to treatment was 3.1 hours; mean age was 54 +/- 10 years; 80% were male; 47% had anterior infarction; 39% had multivessel disease; mean left ventricular ejection fraction was 53 +/- 14%; and mean peak creatine kinase level was 3,820 +/- 3,123 IU/ml. A similar group of 52 (51.5%) patients, treated within 3.3 hours from symptom onset, with a mean postthrombolysis stenosis of 90%, had a positive exercise test. Characteristics of this group were as follows: age was 58 +/- 10 years; 92% were male; 56% had anterior infarction; 40% had multivessel disease; and mean left ventricular ejection fraction was 54 +/- 15%. The peak creatine kinase level associated with the infarction, however, was lower: 2,605 +/- 1,805 IU/ml (p = 0.04). There was no difference in performance at exercise testing with respect to peak systolic pressure, peak heart rate, or time tolerated on the treadmill between the two groups. By multivariate logistic regression, only peak creatine kinase level predicted a negative stress result in the presence of a significant residual stenosis (odds ratio, 4.2; 95% confidence interval, 1.1-16.3). CONCLUSIONS The explanation for the relatively frequent finding of a negative early stress 201Tl tomogram after apparently successful reperfusion appears to be more extensive myocardial necrosis and not delay in therapy or inadequate exercise performance.
Cephalothin-Induced Tachycardia Following Aortic Valve Replacement
Authors: Gerald M. Lemole
Journal: JAMA (1972)

Prophylactic antibiotics, though routinely used by most surgeons for patients undergoing open-heart surgery, are of questionable value and may cause serious side effects. Cephalothin-sodium-induced tachycardia accompanied by hemolysis and hyperpyrexia presents problems of diagnosis. The reported patient's survival is attributed to discontinuation of the drug.
Cooperative function of CCR7 and lymphotoxin in the formation of a lymphoma-permissive niche within murine secondary lymphoid organs
Authors: Armin Rehm, Angela Mensen, Kristina Schradi, Kerstin Gerlach, Stefanie Wittstock, Susann Winter, Gilbert Büchner, Bernd Dörken, Martin Lipp, Uta E. Höpken
Journal: Blood (2011)
The Huxley Lecture on the Function of the Caecum and Appendix: Delivered at the Opening of the Winter Session of Charing Cross Hospital Medical School on October 3rd, 1904
Authors: W. Macewen
Journal: BMJ (1904)

What Huxley owed to the various teachers in Charing Cross iMedical School maybe difficult to gauge and hopeless apportion; doubtless each had its subtle influence.teachers supply material which enables students examinations and nothing more.Here and
Treatment of Invasive Brain Tumors Using a Chain-like Nanoparticle
Authors: Pubudu M. Peiris, Aaron Abramowski, James Mcginnity, Elizabeth Doolittle, Randall Toy, Ramamurthy Gopalakrishnan, Shruti Shah, Lisa Bauer, Ketan B. Ghaghada, Christopher Hoimes, Susann M. Brady-Kalnay, James P. Basilion, Mark A. Griswold, Efstathios Karathanasis
Journal: Cancer Research (2015)

Glioblastoma multiforme is generally recalcitrant to current surgical and local radiotherapeutic approaches. Moreover, systemic chemotherapeutic approaches are impeded by the blood-tumor barrier. To circumvent limitations in the latter area, we developed a multicomponent, chain-like nanoparticle that can penetrate brain tumors, composed of three iron oxide nanospheres and one drug-loaded liposome linked chemically into a linear chain-like assembly. Unlike traditional small-molecule drugs or spherical nanotherapeutics, this oblong-shaped, flexible nanochain particle possessed a unique ability to gain access to and accumulate at glioma sites. Vascular targeting of nanochains to the αvβ3 integrin receptor resulted in a 18.6-fold greater drug dose administered to brain tumors than standard chemotherapy. By 2 hours after injection, when nanochains had exited the blood stream and docked at vascular beds in the brain, the application of an external low-power radiofrequency field was sufficient to remotely trigger rapid drug release. This effect was produced by mechanically induced defects in the liposomal membrane caused by the oscillation of the iron oxide portion of the nanochain. In vivo efficacy studies conducted in two different mouse orthotopic models of glioblastoma illustrated how enhanced targeting by the nanochain facilitates widespread site-specific drug delivery. Our findings offer preclinical proof-of-concept for a broadly improved method for glioblastoma treatment.
Mechanism and Selectivity of the Effects of Halothane on Gap Junction Channel Function
Authors: Ding Sheng He, Janis M. Burt
Journal: Circulation Research (2000)

Volatile anesthetics alter tissue excitability by decreasing the extent of gap junction-mediated cell-cell coupling and by altering the activity of the channels that underlie the action potential. In the present study, we demonstrate, using dual whole-cell voltage-clamp techniques, that coexpression of connexin (Cx) 40 and Cx43 rendered cells more sensitive to uncoupling by halothane than cells that express only Cx40 or only Cx43. The halothane-induced reduction in junctional conductance was caused by decreased channel mean open time and increased channel mean closed time. The magnitude of the effect of halothane on channel open time was least for Cx40-like channels and greatest for heteromeric channels. Thus, the data indicate that halothane gates gap junction channels to the closed state in a dose-dependent and connexin-specific manner. One consequence of the selectivity of halothane is that the profile of single-channel events observed in the presence of halothane may not be quantitatively representative of the population of channels contributing to macroscopic conductance in cells that express more than one connexin. In addition, in tissues that express multiple connexins, such as heart and blood vessels, the capacity of the gap junctions to transmit electrical and chemical signals in the presence of halothane could vary according to the pattern of connexin expression.
Out of hours service in Denmark: evaluation five years after reform
Authors: M. B. Christensen, F. Olesen
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective</b>: Five years after its introduction, to evaluate the 1992 reform in the out of hours service in Denmark. <b>Design:</b> Comparison of data before and after reform. Data were collected from published reports, Danish national health statistics, and the Danish trade union for general practitioners. <b>Setting:</b> Denmark. <b>Main outcome measures:</b> Number of out of hours services; workload of general practitioners; cost of the service; patient satisfaction. <b>Results:</b> Five years after the reform, the percentage of telephone consultations had almost doubled, to 48%. Consultations in doctors9 surgeries were relatively unchanged, but home visits were much reduced, to 18%. The percentage of doctors who worked 5 hours or more out of hours per week dropped from about 70% to about 50%. Overall patient satisfaction in 1995 was high (72%). <b>Conclusion:</b> The organisation of the out of hours service, with a fully trained general practitioner in a telephone triage function, is working satisfactorily. Many calls that previously would have required home visits are now dealt with by telephone or through consultations. The out of hours workload for general practitioners has decreased considerably. <h3>Key messages</h3> The out of hours reform in Denmark has resulted in an organisation with a fully trained general practitioner performing the telephone triage function Hours on call for general practitioners have decreased consideraby Home visits have largely been replaced by telephone consultations Patient satisfaction has declined slightly
A gene for Parkinson's disease?
Authors: C. Hawkes
Journal: BMJ (1996)

In the early 1980s medical opinion favoured an environmental cause for Parkinson's disease. This viewpoint was founded partly on a small study of twins1 and the evidence that drug addicts inadvertently exposed to methylphenyltetrahydropyridine (MPTP) developed an illness very similar to the sporadic form of the disease. Ten years later, the pendulum had swung toward genetic factors. The twin data were reanalysed and deemed inconclusive,2 and several families were identified with apparent autosomal dominant inheritance.

The most convincing family is described by Golbe and others, who identified 41 affected people in four generations.3 The cases were slightly atypical, with young age of onset (mean 46.5 years), predominance of the rigid form of Parkinson's disease, and a rapid course (average 9.7 years to death). However, the …
The nerve growth factor reduces APOBEC3G synthesis and enhances HIV-1 transcription and replication in human primary macrophages
Authors: Thiago Moreno L. Souza, Diego Q. Rodrigues, Caroline P. B. Passaes, Victor Barreto-de-Souza, Renato S. Aguiar, Jairo R. Temerozo, Mariza G. Morgado, Carlos Frederico L. Fontes, Elizabeth G. Araujo, Dumith Chequer Bou-Habib
Journal: Blood (2011)
Expectations of Life: A Study in the Demography, Statistics, and History of World Mortality
Authors: Arnold S. Monto
Journal: JAMA (1991)

A large number of books at various levels of sophistication have been written on the effects of disease and population change on world history. Thus, we are told that the Renaissance was an indirect result of the black death, and George Washington became the first president of the United States because of a typhus epidemic. <i>Expectations of Life</i>is a different sort of book, one that is difficult to classify. It covers wide sweeps of biomedical knowledge, mainly from an historical approach and is thus heavily referenced. In fact, the 98 pages of references may be the most generally useful portion of this book. As stated in the introduction, the author has attempted not only to examine cause-specific mortality over time, but also to review microbiology, epidemiology, and economic history. So much is included that little is covered in detail, but the reader looking for more depth on a particular
Good Medicine and Sound Economics
Authors: G. R. McRobert
Journal: BMJ (1970)

can neurosurgeon, has written a series of essays pleading for more humanity and less prodigal laboratory "science" in the handl- ing of patients.He invokes without, I think, strict applicability, William of Occam's principle Entia non sunt multi- plicanda praeter necessitatem to support his passionate belief that the more thoughtful and able the physician, the fewer laboratory and special tests are required.He de- nounces the demand for "a complete workup" before a careful history is taken and a thorough physical examination per- formed, but curiously, in view of his address on profitable malpractice suits, main- tains that routine skull x-rays are to be avoided in head injuries if palpation reveals no depression and clinical examination no abnormality.His views on the provision of super- specialist surgical centres should be read and re-read by our N.H.S. planners.It
The Value in the Evidence
Authors: Christopher Moriates, Krishan Soni, Andrew Lai, Sumant Ranji
Journal: JAMA Internal Medicine (2013)

The Accreditation Council for Graduate Medical Education mandates that training physicians "incorporate considerations of cost awareness" into practice. However, medical education has traditionally avoided addressing costs, and most residency programs currently lack curricula to fulfill this requirement. With the recent widespread emphasis on unsustainable costs, inefficiencies, and waste in healthcare, the need to appropriately train physicians in this domain is increasingly apparent. In this article, we describe the implementation of a resident-led, case-based cost awareness curriculum for medicine residents at the University of California, San Francisco, sharing our keys to success and defining guiding principles.
HIV Infection in the Dominican Republic
Authors: Kenneth W. Payne
Journal: JAMA (1987)

<h3>To the Editor.—</h3> I read with great interest the article by Koenig et al.<sup>1</sup>As a medical anthropologist, I focused not only on the medical findings but also on the article's social and behavioral claims. I investigated the ethnological record on Haiti and the Dominican Republic (S. Murray, K. Payne, written communication, March 1987)<sup>2</sup>; I also read the medical reports related to acquired immunodeficiency syndrome (AIDS) in both countries. Clearly, a lot of careful attention has been given to serological studies. What puzzles me is why these same researchers so freely accept anecdotal information on the sexual practices of their informants. Like others, Koenig et al uncritically repeat allegations of widespread homosexual activity between tourists and local male prostitutes. Dr Jean-Michel Guerin, who treats AIDS patients in Port-au-Prince and works closely with GHESKIO, reported that "all of his patients—without exception—had denied having sex with tourists" (<i>The New York</i>
Are Risk Stratification Tables the Best Way to Evaluate Model Performance?
Authors: Ralph H. Stern
Journal: Annals of Internal Medicine (2009)

Letters17 March 2009Are Risk Stratification Tables the Best Way to Evaluate Model Performance?Ralph H. Stern, PhD, MD and Dean E. Smith, PhDRalph H. Stern, PhD, MDFrom University of Michigan, Ann Arbor, MI 48109. and Dean E. Smith, PhDFrom University of Michigan, Ann Arbor, MI 48109.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-6-200903170-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Janes and colleagues (1) advocate using risk stratification tables, not the area under the receiver-operating characteristic (ROC) curve or c-statistic, and valuing models that assign a wide range of risks to individuals who were assigned a narrow range of risks by another model. A recent review of this topic (2) reached different conclusions.Simply providing a risk distribution curve (frequency vs. risk in the population) is a more informative way to present the results of a risk stratification model (2), whereas a plot of predicted versus observed risk for each decile of risk is a more informative ...References1. Janes H, Pepe MS, Gu W. Assessing the value of risk predictions by using risk stratification tables. Ann Intern Med. 2008;149:751-60. [PMID: 19017593] LinkGoogle Scholar2. Stern RH. Evaluating new cardiovascular risk factors for risk stratification. J Clin Hypertension. 2008;10:485-8. CrossrefMedlineGoogle Scholar3. Diamond GA. What price perfection? Calibration and discrimination of clinical prediction models. J Clin Epidemiol. 1992;45:85-9. [PMID: 1738016] CrossrefMedlineGoogle Scholar4. Cook NR. Use and misuse of the receiver operating characteristic curve in risk prediction. Circulation. 2007;115:928-35. [PMID: 17309939] CrossrefMedlineGoogle Scholar5. McGeechan K, Macaskill P, Irwig L, Liew G, Wong TY. Assessing new biomarkers and predictive models for use in clinical practice: a clinician's guide. Arch Intern Med. 2008;168:2304-10. [PMID: 19029492] CrossrefMedlineGoogle Scholar6. Lemeshow S, Klar J, Teres D. Outcome prediction for individual intensive care patients: useful, misused, or abused? Intensive Care Med. 1995;21:770-6. [PMID: 8847434] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University of Michigan, Ann Arbor, MI 48109.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAssessing the Value of Risk Predictions by Using Risk Stratification Tables Holly Janes , Margaret S. Pepe , and Wen Gu Are Risk Stratification Tables the Best Way to Evaluate Model Performance? Holly Janes , Margaret S. Pepe , and Wen Gu Metrics 17 March 2009Volume 150, Issue 6Page: 427-428KeywordsConflicts of interestMedical risk factors ePublished: 17 March 2009 Issue Published: 17 March 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Inhibition of mTOR blocks the anti-inflammatory effects of glucocorticoids in myeloid immune cells
Authors: Thomas Weichhart, Michael Haidinger, Karl Katholnig, Chantal Kopecky, Marko Poglitsch, Caroline Lassnig, Margit Rosner, Gerhard J. Zlabinger, Markus Hengstschläger, Mathias Müller, Walter H. Hörl, Marcus D. Säemann
Journal: Blood (2011)