tbuckley/cabot-search huggingface dataset:
Comment on Goldfine et al. Targeting Inflammation Using Salsalate in Patients With Type 2 Diabetes: Effects on Flow-Mediated Dilation (TINSAL-FMD). Diabetes Care 2013;36:4132–4139
Authors: Gary L. Pierce, Kyle Siefers, Lauren Wegman-Points
Journal: Diabetes Care (2014)

We read with interest the study by Goldfine et al. (1) in the recent issue of Diabetes Care that reported that 3 and 6 months of oral salsalate treatment, as part of the multicenter Targeting Inflammation Using Salsalate in Type 2 Diabetes (TINSAL-T2D) trial, had no effect on brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (measurements of endothelium-dependent and -independent dilation, respectively) in patients with type 2 diabetes (T2D). The authors concluded that their findings suggest that 1 ) salsalate does not inhibit vascular inflammation, 2 ) inflammation does not cause endothelial dysfunction in patients with T2D, or 3 ) the potential benefits of salsalate were masked by the unfavorable changes in serum …
Ebola — A Growing Threat?
Authors: Heinz Feldmann
Journal: New England Journal of Medicine (2014)

2009 H1N1 Influenza and Pregnancy -5 Years Later population.Unfortunately, pregnant women continue to become seriously ill with influenza, and some of them die.Research is need ed to further elucidate the reasons why some pregnant women are not vaccinated so that the problems can be addressed.In addition, by implementing the current antiviral treatment recommendations, clinicians can prevent complications in women with influenza.We need to ensure that the information about influenza and pregnancy that has been gained in the 5 years since the 2009 H1N1 pandemic is translated into reductions in the number of illnesses, hospitalizations, and deaths that occur in future influenza seasons.Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
Inhibition of Dietary Hypercholesteremia and Atherogenesis in the Chicken by a New Synthetic Compound
Authors: THOMAS R. BLOHM, LEONARD J. LERNER, TAKASHI KARIYA, MARIE E. WINJE
Journal: Circulation Research (1958)

Addition of 0.1 per cent MER-13 to an atherogenic, high-cholesterol diet largely prevented the development of hypercholesteremia and aortic and coronary artery atheromatosis in cockerels. The hypocholesteremic effect was not obtained when MER-13 was administered following the removal of cholesterol from the diet. It is concluded that MER-13 inhibits absorption of cholesterol from the gastrointestinal tract.
In vivo neural isolation of the canine jejunoileum: temporal adaptation of enteric neuropeptides.
Authors: D K Nelson, M G Sarr, V L Go
Journal: Gut (1991)

This study was designed to assess temporal changes in concentrations of neuromodulatory peptides in plasma and gastrointestinal tissues after in vivo neural isolation of the entire canine jejunoileum. Fasting plasma and transmural biopsy specimens of stomach, duodenum, jejunum, ileum, and colon were obtained from the same dogs before and two, six, and 12 weeks after in situ neural isolation of the entire jejunoileum. Concentrations of vasoactive intestinal peptide, substance P, and neuropeptide Y were determined by quantitative radioimmunoassay. Tissue concentrations of vasoactive intestinal peptide and substance P in the neurally isolated regions increased progressively with time (198% and 217% average maximal increases, respectively), while fasting plasma concentrations changed little. Neuropeptide Y concentrations in plasma and in the jejunoileum were decreased (by 30% to 70%) at two weeks and remained decreased thereafter. Temporal changes in tissue neuropeptide concentrations occur in the neurally isolated jejunum and ileum. These adaptive changes in the neuropeptidergic innervation of the gut may play a role in the alterations in enteric function that occur after extrinsic denervation and after intestinal transplantation.
P07.04 * PROMOTER METHYLATION OF THE LATS1 AND LATS2 GENES IN SCHWANNOMAS
Authors: T. Ohta, J. Oh, M. Mittelbronn, W. Paulus, H. Ohgaki
Journal: Neuro-Oncology (2014)

Schwannoma is a benign nerve sheath tumor that is typically encapsulated and composed of well-differentiated Schwann cellswhich comprises 5-10% of all intracranial tumors in adults. Approximately 90% of schwannomas are solitary and sporadic, whereas ∼4% are considered to arise in the setting of neurofibromatosis type 2 (NF2) syndrome by NF2 germline mutations. The molecular basis of sporadic schwannomas is not fully understood, other than frequent NF2 mutations (∼60%). LATS1 and the related LATS2 are downstream molecules of NF2 and negative regulators of the YAP oncogene in the Salvador/Warts/Hippo (SWH) signaling pathway. Expression of these genes is reduced due to promoter methylation in a variety of neoplasms including gliomas. In the present study, methylation-specific PCR revealed promoter methylation of the LATS1 and LATS2 in 15 of 91 (16%) and 32 of 91 (35%) schwannomas, respectively. These alterations were significantly more frequent in spinal than in peripheral schwannomas (23% vs 3% for LATS1, P = 0.0171; 42% vs 21% for LATS2, P = 0.0386). LATS1 methylation was also detected in 3 of 4 schwannomatosis cases. Furthermore, neurofibroma / schwannoma hybrid tumors showed promoter methylation in LATS1 (3/14; 21%) and LATS2 (8/14; 57%). LATS1 and LATS2 promoter methylation were largely mutually exclusive, and there was a significant negative correlation (P = 0.003); only 10 cases had methylation in both genes. These results suggest that LATS1 and LATS2 promoter methylation may be additional molecular mechanisms resulting in an abnormal SWH pathway in schwannomas and related tumors.
Neoadjuvant Chemotherapy with Docetaxel and Cisplatin in Patients with High-Risk Resectable Bladder Carcinoma: Long Term Results
Authors: A Bamias, C Deliveliotis, A Karayiannis, I Varkarakis, I Zervas, D Pantazopoulos, D Gika, M.A Dimopoulos
Journal: European Urology (2004)
Presentation of Cytosolic Glycosylated Peptides by Human Class I Major Histocompatibility Complex Molecules in Vivo
Authors: John S. Haurum, Ingelise Bjerring Høier, Gemma Arsequell, Anne Neisig, Gregorio Valencia, Jesper Zeuthen, Jacques Neefjes, Tim Elliott
Journal: The Journal of Experimental Medicine (1999)

Antigens presented by class I major histocompatibility complex (MHC) molecules for recognition by cytotoxic T lymphocytes consist of 8–10-amino-acid-long cytosolic peptides. It is not known whether posttranslationally modified peptides are also presented by class I MHC molecules in vivo. Many different posttranslational modifications occur on cytoplasmic proteins, including a cytosolic O-β-linked glycosylation of serine and threonine residues with N-acetylglucosamine (GlcNAc). Using synthetic glycopeptides carrying the monosaccharide O-β-GlcNAc substitution on serine residues, we have shown that glycopeptides bind efficiently to class I MHC molecules and elicit a glycopeptide-specific cytotoxic T lymphocyte response in mice. In this study, we provide evidence that peptides presented by human class I MHC molecules in vivo encompass a small, significant amount of glycopeptides, constituting up to 0.1% of total peptide. Furthermore, we find that carbohydrate structures present on glycopeptides isolated from class I MHC molecules are dominated by the cytosolic O-β-GlcNAc substitution, and synthetic peptides carrying this substitution are efficiently transported by TAP (transporter associated with antigen presentation) into the endoplasmic reticulum. Thus, in addition to unmodified peptides, posttranslationally modified cytosolic peptides carrying O-β-linked GlcNAc can be presented by class I MHC molecules to the immune system.
Clinical Significance of the Pulmonary Vasodilator Response During Short-term Infusion of Prostacyclin in Primary Pulmonary Hypertension
Authors: Olivier Raffy, Réza Azarian, François Brenot, Florence Parent, Olivier Sitbon, Patrick Petitpretz, Philippe Hervé, Pierre Duroux, A. Tuan Dinh-Xuan, Gérald Simonneau
Journal: Circulation (1996)

The short-term vasodilator response to prostacyclin (PGI2) in patients with primary pulmonary hypertension (PPH) is not only unpredictable but also extremely variable in magnitude. In this retrospective study, we attempted to evaluate in a nonselected population of patients with PPH the degree of vasodilatation achieved during short-term infusion of PGI2 and to investigate whether patients with PPH differed in terms of baseline characteristics and prognoses, according to the level of vasodilatation achieved during initial testing with PGI2.Between 1984 and 1992, 91 consecutive patients with PPH underwent catheterization of the right side of the heart with a short-term vasodilator trial with PGI2 (5 to 10 ng.kg-1.min-1). According to the level of vasodilatation achieved during PGI2 infusion, patients were divided into three groups: nonresponding (NR, n = 40), moderately responding (MR, n = 42), and highly responding (HR, n = 9) patients. All three groups were defined by a decrease in total pulmonary resistance index (TPRi) of < 20%, between 20% and 50%, and > 50%, respectively, relative to control values. Prolonged oral vasodilator therapy was subsequently started only in MR and HR patients. All patients had long-term oral anticoagulant therapy. The survival rate at 2 years (transplant recipients excluded) was significantly higher in HR patients compared with NR and MR patients (62% versus 38% and 47% survivors, respectively; P < .05). Comparisons between groups showed no significant differences in baseline hemodynamics or clinical characteristics except for a longer time between onset of symptoms and diagnosis (ie, first catheterization) of PPH in HR patients than in NR and MR patients (71 +/- 61 versus 35 +/- 34 and 21 +/- 21 months, respectively; P < .05).In this study, patients with PPH exhibiting a decrease in TPRi > 50% during short-term PGI2 challenge at the time of diagnosis had longer disease evolutions and better prognoses than patients with a lower vasodilator response.
Malaria Therapy: The Value of the Randomized Controlled Trial-Reply
Authors: Paul D. Stolley
Journal: JAMA (1993)

In Reply.  —Dr Phillips reminds us of Dr Zelen's suggestions for alternatives to a strictly randomized trial. However, if those patients who choose not to give consent are different from those who do give consent on characteristics related to prognosis, interpretation of trial results will be difficult. This is a limitation of this alternative design.  Dr Heimlich cites the widespread use of malariotherapy, even 30 years after the introduction of antibiotics, the award of the Nobel Prize to Warner-Jauregg in 1927, and the many uncontrolled case series as proof of its efficacy. These are all of great historical interest, but in our article we show how these anecdotal and case series data fail to settle the issue of efficacy.  Can one demonstrate the efficacy of a treatment without an RCT? Perhaps medicine and epidemiology will develop new methods. In the meantime, the RCT provides objective evaluation of a treatment—a clear
Book Review A Time to Be Born and a Time to Die: The ethics of choice (Starkoff Institute Studies in Ethics and Contemporary Moral Problems.) Edited by Barry S. Kogan. 267 pp. Hawthorne, N.Y., Aldine de Gruyter, 1991. $42.95 (cloth); $22.95 (paper).
Authors: Edmund D. Pellegrino
Journal: New England Journal of Medicine (1992)
The discontinuity between rules and similarity
Authors: Peter F. Dominey
Journal: Behavioral and Brain Sciences (2005)

In arguing for a rules-similarity continuum, Pothos should demonstrate that a single process or mechanism (a neural network model, for example) can handle the entire continuum. Pothos deliberately avoids this exercise as beyond the scope of the current research. In this context, I will present simulation, neuropsychological, neurophysiological, and experimental psychological results, arguing against the continuity hypothesis.
Haemophilus influenzae Pericarditis and Empyema With Thyroiditis in an Adult
Authors: Robert N. Alsever
Journal: JAMA (1974)

A 26-year-old woman had acute thyroiditis. Forty-eight hours later, pericardial tamponade and empyema developed requiring surgical intervention.<i>Haemophilus influenzae</i>type B was recovered from blood and pleural and pericardial fluid. Treatment with chloramphenicol, and later, ampicillin sodium resulted in recovery. Challenge with<i>H influenzae</i>antigen six months later was followed by a brisk rise in bactericidal antibody, suggesting the patient was nonimmune. Because of the apparently increasing number of such nonimmune adults,<i>H influenzae</i>must be considered as a cause of similar life-threatening infections in this age group. (<i>JAMA</i>230:1426-1427, 1974)
Separate and Equitable Promotion Tracks for Clinician-Educators
Authors: Victoria Manion Fleming, Nancy Schindler, Gary J. Martin, Debra A. DaRosa
Journal: JAMA (2005)

MOST ACADEMIC MEDICAL CENTERS (AMCS) HAVE missions that aim for excellence in 3 areas: education, research, and patient care. For decades, “triple-threat” faculty members were able to substantively contribute to all 3. However, heightened competition for research grants, changes in the health care delivery system, more sophisticated instructional and evaluation methods, and increased requirements to account for time and productivity make it less feasible for individual faculty to significantly contribute to all 3. Instead, faculty members are likely to focus their efforts in 1 or 2 of these areas. Although exceptions exist, physician faculty members focus either on patient care and research or on patient care and education. The problem is that promotion and tenure systems work well for faculty members pursuing the former but not as well for those focusing on the latter. For instance, 1 report found that, compared with research faculty, the odds of holding a higher academic rank were 85% lower for academic clinicians and 69% lower for teacher-clinicians. In another report, faculty devoting more than 50% of their time to clinical care were more likely to be on a nontenure track and more likely to report slower career progress than those devoting less than 50% of their time to clinical care. In a third report, the time to promotion was significantly shorter for physician-scientists (with 80% designated research time) than for clinician-scholars (with 30% research time). If this issue is not resolved, AMCs run the risk that faculty charged with patient care and education will view their contributions as having limited value, which will decrease motivation and reduce incentives for future efforts. In this article, we briefly review the evolution and early promise of faculty promotion and tenure tracks. We explore ways clinician-educators are designated within academic promotion and tenure models, address the value of these faculty to the AMC system and the challenges they face, examine measurement and evaluation issues, and offer suggestions for change. History of Faculty Tracks
Cigarette Smoking and Nicorette Gum
Authors: JOHN W. RICHARDS
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 March 1987Cigarette Smoking and Nicorette GumJOHN W. RICHARDS JR., M.D.JOHN W. RICHARDS JR., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-106-3-482_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: While waiting at the baggage turnstyle in the National Airport in Washington, D.C, I overheard an interesting conversation.Woman 1: It's really rough when you get to the plane late and have to sit in the nonsmoking section. [She reached for a cigarette and began to light up.]Woman 2: Yeah, I know what you mean. [She did likewise.]Woman 1: It's getting worse all the time. They've even banned smoking where I work. If it weren't for Nicorette gum, I'd have to quit smoking.Woman 2: Hey, that's a great idea. Can you loan me some... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Medical College of Georgia Augusta, GA 30912-6500 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNicotine Chewing Gum and Group Counseling in Smoking Cessation 1 March 1987Volume 106, Issue 3Page: 482-483KeywordsNicotine Issue Published: 1 March 1987 PDF downloadLoading ...
Human<i>Borrelia miyamotoi</i>Infection in the United States
Authors: Peter J. Krause, Sukanya Narasimhan, Gary P. Wormser, Lindsay Rollend, Erol Fikrig, Timothy Lepore, Alan Barbour, Durland Fish
Journal: New England Journal of Medicine (2013)

tory tract infections cautioning against their misuse. 3Linezolid may become subject to similar misuse by physicians who prescribe it for the treatment of undiagnosed infections, as has been reported. 4This observation is consistent with our own at a tertiary care hospital in India.In the recent guidelines on pneumonia from India, we have called for restrictions on the use of linezolid. 5It is desirable that future guidelines on respiratory and other infections advise against its use early in the course of an infection.
Impact of a Psychoeducational Family Intervention on Caregivers of Stabilized Bipolar Patients
Authors: M. Reinares, E. Vieta, F. Colom, A. Martínez-Arán, C. Torrent, M. Comes, J.M. Goikolea, A. Benabarre, J. Sánchez-Moreno
Journal: Psychotherapy and Psychosomatics (2004)

&lt;i&gt;Background:&lt;/i&gt; Environmental stress has an important role in the course of bipolar disorder. Some findings have shown that family beliefs about the illness could predict family burden, and this burden could influence the outcome of bipolar disorder. To the best of our knowledge, there is scant information about the effects of family intervention on the caregiver’s burden in bipolar disorder. The aim of this study was to assess the effects of psychoeducational family intervention on bipolar patients’ caregivers, including the assessment of the caregiver’s burden. &lt;i&gt;Methods:&lt;/i&gt; 45 medicated euthymic bipolar outpatients were randomized into an experimental and a control group. Relatives of patients from the experimental group received 12 psychoeducational, 90-min sessions about bipolar disorder and coping skills. The caregivers’ knowledge of bipolar disorder, the relationship subscales of the Family Environment Scale, and the family burden subscales from an adapted version of the Social Behavior Assessment Schedule were assessed for both caregiver groups before and after the intervention. &lt;i&gt;Results:&lt;/i&gt; Psychoeducated caregivers significantly improved their knowledge of bipolar disorder and reduced both the subjective burden and the caregiver’s belief about the link between the objective burden and the patient. No significant differences were found in the objective burden nor in the family relationship subscales. &lt;i&gt;Conclusions:&lt;/i&gt; These preliminary results suggest that psychoeducational intervention on caregivers of bipolar patients may improve the caregiver’s knowledge of the illness, reduce their distress or subjective burden and alter their beliefs about the link between the disruptions in their life and the patient’s illness.
The Urinary Metanephrine-to-Creatinine Ratio for the Diagnosis of Pheochromocytoma
Authors: Emmanuel Heron
Journal: Annals of Internal Medicine (1996)

Objective: To compare the operating characteristics of two tests for diagnosing pheochromocytoma: 1) measurement of the ratio between urinary metanephrine and creatinine levels and 2) measurement of urinary metanephrine levels alone. A second objective was to ascertain the reasons for false-positive test results. Design: Cross-sectional study. Setting: Hypertension referral center. Patients: 1013 patients referred for hypertension and tested for pheochromocytoma. Measurements: 24-hour urinary levels of metanephrine (measured using liquid chromatography) and creatinine. The presence of pheochromocytoma was confirmed at surgery. In patients with positive test results, the absence of pheochromocytoma was documented by negative results of retests and imaging procedures. Results: Of 58 patients with increased metanephrine levels or increased metanephrine-to-creatinine ratios, 20 had pheochromocytoma and 38 did not. Of the 38 patients without pheochromocytoma, 15 had high metanephrine levels but normal metanephrine-to-creatinine ratios. The respective operating characteristics of measurement of urinary metanephrine levels and measurement of the metanephrine-to-creatinine ratio were as follows: sensitivity, 95% and 100%; specificity, 98% and 98%; positive predictive value, 46% and 47%; and negative predictive value, 100% and 100%. In 13 of the 23 patients who had a high metanephrine-to-creatinine ratio, various acute events may have caused hypersecretion of catecholamines. Conclusions: Measurement of the metanephrine-to-creatinine ratio is a sensitive and specific test for pheochromocytoma. However, acute events may increase urinary metanephrine excretion to the level that occurs with tumors.
Autism and Creativity: Is there a Link between Autism in Men and Exceptional Ability?
Authors: Iain McClure
Journal: BMJ (2004)

Michael Fitzgerald Brunner-Routledge, £29.99/$47.95 pp 304 ISBN 1 58391 213 4 Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> We hear a lot about autism these days, usually in connection with its devastatingly early onset and bleak prognosis. It is therefore of interest when a recognised authority on the subject claims that most of those whom he cites as “the intellectual giants of the twentieth century” (including Einstein, Freud, Yeats, the philosophers Russell and Wittgenstein, and the mathematicians Ramanujan and Turing) had high functioning autism or … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Highly Active Antiretroviral Therapy and the Incidence of Non–AIDS-Defining Cancers in People With HIV Infection
Authors: Thomas Powles, David Robinson, Justin Stebbing, Jonathan Shamash, Mark Nelson, Brian Gazzard, Sundhiya Mandelia, Henrik Møller, Mark Bower
Journal: Journal of Clinical Oncology (2008)

The effect of highly active antiretroviral therapy (HAART) on the incidence of non-AIDS-defining cancers (NADCs) is unclear.We have investigated the occurrence of NADCs in a prospective cohort of 11,112 HIV-positive individuals, with 71,687 patient-years of follow-up. Standardized incidence ratios (SIRs) were calculated using general population incidence data. We investigated the effect of calendar period, HIV parameters, and immunologic and treatment-related factors on the incidence of these cancers using univariate and multivariate analyses.The SIR for all NADCs was 1.96 (95% CI, 1.66 to 2.29). There was no significant excess in incidence in the pre-HAART era (1983 to 1995; SIR, 0.95; 95% CI, 0.58 to 1.47). However, the incidence increased in the early HAART period (1996 to 2001) and remains elevated in the most recent established HAART period (2002 to 2007; SIR, 2.05; 95% CI, 1.51 to 2.72, and SIR 2.49; 95% CI, 2.00 to 3.07, respectively). Multivariate analysis showed that use of HAART (hazard ratio [HR] = 1.64; 95% CI, 1.13 to 2.39) and a nadir CD4 count less than 200/microL (HR = 1.67; 95% CI, 1.10 to 2.54) were associated with an increased risk. Only the non-nucleoside reverse transcriptase inhibitors (NNRTIs) were associated with a significantly increased risk of NADCs (HR = 1.45; 95% CI, 1.01 to 2.08). Much of this association was attributable to an increased risk of Hodgkin's lymphoma with NNRTIs (HR = 2.20; 95% CI, 1.03 to 4.69).Since the introduction of HAART, there has been a significantly increased risk of NADCs, which has now stabilized. A number of factors are associated with this increased risk, including HAART use. There may be an association between the use of NNRTIs and the development of Hodgkin's lymphoma.