tbuckley/cabot-search huggingface dataset:
Ubiquitination and Proteasomal Degradation of Nucleophosmin-Anaplastic Lymphoma Kinase Induced by 17-Allylamino-Demethoxygeldanamycin
Authors: Paolo Bonvini, Henry Dalla Rosa, Nadia Vignes, Angelo Rosolen
Journal: Cancer Research (2004)

Abstract Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is a constitutively active fusion tyrosine kinase involved in lymphomagenesis of human anaplastic large cell lymphomas (ALCL), the maturation and activity of which depend on the association with the heat shock protein (hsp) 90 protein chaperone. Targeting hsp90 by the ansamycins geldanamycin and 17-allyl-amino-demethoxygeldanamycin (17-AAG) promotes degradation of several proteins through the ubiquitin-proteasome pathway, including oncogenic Raf, v-Src, erbB2, and BCR-ABL. We have previously shown that 17-AAG prevents hsp90/NPM-ALK complex formation and fosters NPM-ALK turnover, perhaps through its association with the hsp70 chaperone. Here, we show that inhibition of the proteasome activity by the potent and specific compound pyrazylcarbonyl-Phe-Leu-boronate (PS-341) blocks 17-AAG-induced down-regulation of NPM-ALK, which becomes detergent-insoluble and relocates into ubiquitin-rich perinuclear vesicles that represent aggregated polyubiquitinated forms of the protein. Kinase activity was not mandatory for proteasomal degradation of NPM-ALK, because kinase-defective NPM-ALK was even more rapidly degraded upon 17-AAG treatment. Prolonged exposure to the proteasome inhibitor was shown to trigger caspase-3-mediated apoptosis in proliferating ALCL cells at nanomolar concentrations. However, we verified that the accumulation of detergent-insoluble NPM-ALK in ALCL cells was not a spurious consequence of PS341-committed apoptosis, because caspase inhibitors prevented poly(ADP-ribose) polymerase cleavage whereas they did not affect par-titioning of aggregated NPM-ALK. In line with these observations, the carboxyl hsp70-interacting ubiquitin ligase (CHIP), was shown to increase basal ubiquitination and turnover of NPM-ALK kinase, supporting a mechanism whereby NPM-ALK proceeds rapidly toward hsp70-assisted ubiquitin-dependent proteasomal degradation, when chaperoning activity of hsp90 is prohibited by 17-AAG.
THIAZOLIDINEDIONES ON DISCHARGE AFTER DRUG ELUDING STENT IMPLANTATION DECREASES MORTALITY
Authors: Dhavalkumar B. Patel, Joseph Lindsay, Zhenyi Xue, Rebecca Torguson, Rebecca Torguson, William O. Suddath, Lowell F. Satler, Augusto D. Pichard, Kenneth M. Kent, Ron Waksman
Journal: Journal of the American College of Cardiology (2011)
The EUTOS CML score aims to support clinical decision-making
Authors: Verena Hoffmann, Michele Baccarani, Joerg Hasford, Joelle Guilhot, Susanne Saussele, Gianantonio Rosti, François Guilhot, Kimmo Porkka, Gert Ossenkoppele, Doris Lindoerfer, Bengt Simonsson, Markus Pfirrmann, Rüdiger Hehlmann
Journal: Blood (2012)
In Utero Placement of Aortopulmonary Shunts
Authors: V. Mohan Reddy, Barbara Meyrick, Jackson Wong, Andras Khoor, John R. Liddicoat, Frank L. Hanley, Jeffrey R. Fineman
Journal: Circulation (1995)

Background The development of pulmonary hypertension and its associated increased vascular reactivity is a common accompaniment of congenital heart disease with increased pulmonary blood flow. Although the morphology of the pulmonary vascular changes is well described, the mechanisms of vascular remodeling and increased reactivity remain incompletely understood. Methods and Results To elucidate these mechanisms, we established an accurate and reliable experimental model of pulmonary hypertension with increased pulmonary blood flow. An aortopulmonary shunt was created with an 8.0-mm expanded polytetrafluoroethylene vascular graft in 11 late-gestation fetal lambs. At 1 month of age, shunted lambs had a pulmonary–to–systemic blood flow ratio of 2.2±1.2. Compared with 11 age-matched control lambs, mean pulmonary arterial pressure (44.8±11.7 versus 16.2±2.9 mm Hg) and the ratio of pulmonary to systemic arterial pressure were significantly increased ( P &lt;.05). Pulmonary vascular resistance was not significantly increased. The pulmonary vasoconstricting response to the infusion of U46619 (a thromboxane A 2 mimic) or acute alveolar hypoxia also was augmented in the shunted lambs. Morphometric analysis of the barium-filled pulmonary artery bed revealed medial hypertrophy, abnormal extension of muscle distally into the walls of the intra-acinar arteries, and increased numbers of barium-filled intra-acinar arteries. Conclusions In utero placement of aortopulmonary shunts reproduces the aberrant hemodynamic state of children with congenital heart disease with left-to-right shunts; postnatal pulmonary hypertension, increased pulmonary blood flow, and vascular remodeling. In addition, the lambs have a unique paradoxical increase in pulmonary vascular volume that attenuates an increase in pulmonary vascular resistance. This experimental preparation provides a useful and consistent model for the study of the pathogenesis of pulmonary hypertension.
Induction of UV light tolerance by PUVA in patients with polymorphous light eruption
Authors: F. GSCHNAIT, H. HONIGSMANN, W. BRENNER, P. FRITSCH, K. WOLFF
Journal: British Journal of Dermatology (1978)

A tan induced by 8-methoxypsoralen-long wave ultraviolet light has proved an effective photoprotective sunscreen in 5 patients with long wave ultraviolet light-induced polymorphic light eruption.
Whole government approach is needed to improve health across Europe, says WHO
Authors: P. Dinsdale
Journal: BMJ (2011)

A major shift in the way public health is managed across Europe will be needed in future if all countries are to achieve the best health standards for their citizens, says the World Health Organization.

Launching its draft health policy for the next 10 years, Health 2020, the WHO’s regional director for Europe, Zsuzsanna Jacob, said that more “horizontal, inclusive approaches” to health governance were needed, involving all sectors of society and people themselves.

“This necessitates a ‘whole of government’ approach towards health and wellbeing, which is at the heart of Health 2020,” said Ms Jacob. In its strategy document, WHO says that health across the European region is improving, but not by enough, and that, considering the burden of non-communicable diseases and communicable disease, governments could “do better” with what they …
Safety of maximal exercise testing in patients at high risk for ventricular arrhythmia.
Authors: D Z Young, S Lampert, T B Graboys, B Lown
Journal: Circulation (1984)

While maximal exercise testing is useful for detection of arrhythmias and assessment of antiarrhythmic drug efficacy, few reports have documented the safety of this procedure in patients with malignant ventricular arrhythmias. We reviewed the complications of symptom-limited exercise in 263 patients with such arrhythmias who underwent a total of 1377 maximal treadmill tests. Seventy-four percent of the population studied had a history of ventricular fibrillation or hemodynamically compromising ventricular tachycardia and the remainder had experienced ventricular tachycardia in the setting of either recent myocardial infarction or poor left ventricular function. A complication was defined as the occurrence of arrhythmia during exercise testing--ventricular fibrillation, ventricular tachycardia, or bradycardia--that mandated immediate medical treatment (cardioversion, use of intravenous drugs, or closed-chest compression). Complications were noted in 24 patients (9.1%) during 32 tests (2.3%), whereas 239 patients (90.9%) were free of complication during 1345 tests (97.7%). There were no deaths, myocardial infarctions, or lasting morbid events. Clinical descriptors associated with complications included male sex, presence of coronary artery disease, and a history of exertional arrhythmia (p less than .05). Clinical variables previously considered to confer increased risk during exercise, such as poor left ventricular function, high-grade ventricular arrhythmias (Lown grade 4A or 4B) before or during exercise, exertional hypotension, and ST depression, were not predictive of complications (p greater than .05). Occurrence of a complication was also unaffected by the use of antiarrhythmic drugs at the time of exercise (chi square = 0.19, p greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
PNEUMONIA COMPLICATED BY MENINGITIS.
Authors: W. H. AXTELL
Journal: JAMA (1906)

I report the following because of its infrequent occurrence: <h3>History.</h3> —Mrs. W., aged 32, family history negative, very sparely built, has one son 5 years of age, and has had no illness since childhood. The present illness began Nov. 28, 1904. In the morning she had a sharp chill, followed in the afternoon by high temperature and a slight pain in the right lower chest. During that night and the forenoon of the next day the pain became very much augmented. I saw her at 3 p. m. on November 29. Her temperature then was 105 1/5; pulse, 140; respiration, 36 and panting in character; she was cyanotic. Auscultation revealed crepitant râles in the lower lobe of the right lung in the axillary line. The area of dullness on percussion was about the size of a silver dollar. The pleurisy extended over a greater part of the right lateral chest.
A3-01: Correlation of tumor response and survival in advanced NSCLC patients treated with Paclitaxel plus Carboplatin (PC) vs Paclitaxel plus Carboplatin plus Gemcitabine (PCG)
Authors: Adriano Paccagnella, Francesco Oniga, Alessandra Bearz, Adolfo Favaretto, Fausto Barbieri, Antonio Chella, Giovanni Ceresoli, Rita Biason, Paola D'Amanzo, Maria Grazia Ghi
Journal: Journal of Thoracic Oncology (2007)
Imaging-based, non-radioactive measurements of natural killer cell activity provides comparable results as classic chromium release assays but with fewer cells and less labor
Authors: Srividya Sundararaman, Kinga Karacsony, Diana Roen, Paul V Lehmann
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Natural Killer Cell activity has traditionally been assessed by detecting the lysis of tumor cells in The Chromium Release assay. This classic assay relies on radioactive labels, is laborious, and requires substantial quantities of patient blood. Moreover the Chromium Release
Doctors fail to see the joke
Authors: R. Dobson
Journal: BMJ (2002)

A patient laughs four times during an average consultation with a doctor, according to new research.

But doctors rarely reciprocate, say the researchers, who videotaped 250 consultations in order to count the number of instances of laughter, smiles, and “smiling voices” involving the doctor or the patient or both.

The researchers, from the University of Helsinki, highlight some of the subjects of conversation that triggered laughter in the patients—varicose veins, pain in the leg, yeast …
When Previously Expressed Wishes Conflict With Best Interests
Authors: Alexander K. Smith, Bernard Lo, Rebecca Sudore
Journal: JAMA Internal Medicine (2013)

Rising use of advance directives has made surrogate decision making both easier and harder. In many cases, these directives help guide decision making for patients who have lost decision-making capacity. In some cases, however, directives may conflict with what physicians or surrogates view as what is in the patient's best interest. These conflicts can place substantial emotional and moral burdens on physicians and surrogates, and there is little practical guidance for how to address them. We propose a 5-question framework for untangling the conflict between advance directives and best interests of a patient with a surrogate decision maker: (1) Is the clinical situation an emergency? (2) In view of the patient's values and goals, how likely is it that the benefits of the intervention will outweigh the burdens? (3) How well does the advance directive fit the situation at hand? (4) How much leeway did the patient provide the surrogate for overriding the advance directive? (5) How well does the surrogate represent the patient's best interests? We use 2 clinical cases with contrasting outcomes to demonstrate how this framework can help resolve common dilemmas.
A CASE OF EPISTAXIS
Authors: EDMUND R. BLAAUW
Journal: JAMA (1910)

The article about epistaxis inThe Journal, April 30, induces me to relate the following case: On March 25 a 19-year-old boy consulted me for very severe headache. About two weeks previously he had influenza and four days previously his head began to pain him, so that sleep was impossible; his nose began to run at the same time. Percussion on the left frontal sinus was painful; also pressure in the left upper inner orbital corner. The left middle turbinate was swollen and, after depletion by cocain and epinephrin (adrenalin), pus came from below and above the turbinate. My diagnosis was left frontal sinusitis and ethmoiditis. The symptoms had not improved markedly the next day, so I removed the middle concha. No abnormality was noticed, the headache was controlled, and packing removed the following week. Eight days after the operation slight nosebleed occurred, but the cotton plug soaked in hydrogen
The diagnosis and management of ductal carcinoma in-situ of the breast
Authors: D. P. Winchester, J. M. Jeske, R. A. Goldschmidt
Journal: CA A Cancer Journal for Clinicians (2000)

The widespread utilization of screening mammography has produced a shift in the stage of breast cancer at diagnosis in the US: Currently, 12% to 15% of newly diagnosed breast cancer cases annually are ductal carcinoma in-situ (DCIS). The diagnosis is made, in at least 90% of patients, with mammography. Only about 10% of patients will have a palpable mass. The accurate characterization and visualization of calcifications typically requires magnification of mammographic imaging. The morphology of the calcifications is generally considered to be the most important factor in differentiating benign from malignant formations. Round and uniform shapes are more likely to be benign, while linear and heterogeneous morphologies are associated with DCIS. Following a complete mammographic work-up, most suspicious lesions are potential candidates for a stereotactic core needle biopsy. Ten percent to 50% of patients initially diagnosed with atypical ductal hyperplasia by needle biopsy have subsequently been surgically diagnosed with cancer near the biopsy site. Due to this relatively high incidence of co-existent carcinoma, a needle biopsy diagnosis of atypical ductal hyperplasia necessitates subsequent surgical excision. The most important change in our thinking about DCIS was from a monolithic view, conceiving of DCIS as a single disease highly likely to invade if left untreated, to the realization that DCIS represents a non-obligate precursor with a variable risk of progression, depending on a combination of factors, such as histology, lesion, size, and margin status. In discussing treatment options, patients should understand that local recurrence following total mastectomy is rare and that this is the procedure of choice for disease that cannot be adequately encompassed with a breast-conserving approach. If the patient and her surgeon are in agreement about proceeding with a breast-conserving approach, there needs to be a clear understanding of the incidence and implications of local recurrence. In all such discussions with newly diagnosed patients, however, it is essential to emphasize the excellent prognosis with this disease, irrespective of the surgical approach.
Almost Off the Actuarial Curve
Authors: Julian Jacobs
Journal: JAMA (1982)

The snowstorm came as a surprise, but not an unexpected one. The same was true of the substernal burning. Both my parents have adult-onset diabetes; my father survived an infarct at 57; my younger brother died suddenly at 29 in 1965.I have controlled hypertension and an abnormal blood lipid pattern and am undeniably a type A personality. The last thing I achieved in a relaxed manner was winning the spelling bee in the sixth grade. Because of the snow, I left my car on campus and had just climbed a long hill on the way home when the burning began. I stopped and feigned an interest in the cars struggling up the hill. I remembered a chest pain years previously as I had walked to the flight gate to meet my favorite aunt arriving for my brother's funeral. More severe by far, the ancient pain had also disappeared on pausing,
Psychosocial Functioning in Consultation-Liaison Psychiatry Patients: Influence of Psychosomatic Syndromes, Psychopathology and Somatization
Authors: Piero Porcelli, Antonello Bellomo, Roberto Quartesan, Mario Altamura, Salvatore Iuso, Ida Ciannameo, Massimiliano Piselli, Sandro Elisei
Journal: Psychotherapy and Psychosomatics (2009)

&lt;i&gt;Background:&lt;/i&gt;This study investigated whether the Diagnostic Criteria for Psychosomatic Research (DCPR) were able to predict psychosocial functioning in addition to psychiatric diagnoses and somatization in consultation-liaison psychiatry (CLP) patients. &lt;i&gt;Method:&lt;/i&gt; A consecutive sample of 208 CLP patients were recruited and assessed for sociodemographic and medical data, psychopathology (SCID), psychosomatic syndromes (DCPR structured interview) and somatization (SCL-90-R SOM scale and multisomatoform disorder, MSD). The main endpoints were the mental and physical components of psychosocial functioning (SF-36). &lt;i&gt;Results:&lt;/i&gt; A total of 185 (89%) patients had any psychiatric diagnosis, 51 (25%) had MSD positive criteria, 176 (85%) had any DCPR syndrome, and 105 (51%) had multiple DCPR syndromes. Although psychiatric and psychosomatic syndromes were variously associated with psychosocial functioning, hierarchical regression and effect size analyses showed that only DCPR syndromes, particularly demoralization and health anxiety, with somatization but not DSM-IV psychopathology independently predicted poor psychosocial functioning. &lt;i&gt;Conclusions:&lt;/i&gt;The presence of psychosomatic syndromes, assessed with DCPR criteria, and high levels of somatization had larger effect size and were independent predictors of the mental and physical components of psychosocial dysfunction, over and above psychopathology. The DCPR classification can provide CLP professionals with a set of sensitive diagnostic criteria for a comprehensive clinical evaluation of psychosomatic syndromes that might play a significant mediating role in the course and the outcome of medical patients referred for psychiatric consultation.
Psychological Reaction to Loss of One Eye
Authors: P. T. Merlin
Journal: BMJ (1946)

<h3>Objectives</h3> To explore patient and stakeholder perspectives on primary respiratory care for people with severe mental illness (SMI) and comorbid obstructive airways disease (OAD). <h3>Design</h3> Qualitative, semistructured qualitative interviews were undertaken with a purposive sample of people with a diagnosis of SMI (bipolar illness, schizophrenia, affective disorder with psychosis) and comorbid asthma or chronic obstructive pulmonary disease. Transcribed data were analysed using an interpretive phenomenological approach. Study results were discussed with stakeholders. <h3>Setting</h3> Eight UK general practices. <h3>Participants</h3> 16 people aged 45–75 years, with SMI and comorbid asthma or chronic obstructive pulmonary disease, were interviewed. Twenty-one people, four with lived experience of SMI and seventeen health/social care/third sector practitioners, participated in discussion groups at a stakeholder event. <h3>Results</h3> Participants described disability and isolation arising from the interplay of SMI and OAD symptoms. Social support determined ease of access to primary care. Self-management of respiratory health was not person-centred as practitioners failed to consider individual needs and health literacy. Participants perceived smoking cessation impossible without tailored support. Less than half of the practices facilitated personalised access to timely primary care and continuity. Overall, there was a reliance on urgent care if service adaptations and social support were lacking. The stakeholder group expressed concern about gaps in care, the short-term funding of community organisations and fear of loss of benefits. Potential solutions focused on supported navigation of care pathways, relational continuity, individual and community asset building and the evolving social prescriber role. <h3>Conclusion</h3> This study suggests that despite UK guidelines and incentives to optimise physical healthcare, primary care fails to consistently deliver integrated biopsychosocial care for patients with SMI and OAD. Collaborative, personalised care that builds social capital and tailors support for self-management is needed, alongside service-level interventions to enhance access to healthcare for patients with comorbid SMI and OAD.
Alzheimer's society welcomes Reagan's "bravery"
Authors: C Court
Journal: BMJ (1994)

The former American president Ronald Reagan has taken the unprecedented step of sending a handwritten letter to the American people revealing that he is suffering from Alzheimer's disease. His action has been welcomed in Britain by the Alzheimer's Disease Society as “a brave decision.”

Mr Reagan is the first person of such international repute to admit publicly to suffering from Alzheimer's disease, and his letter is being hailed as a great boost to …
What is a good death?: Life is all we have
Authors: N. Pik
Journal: BMJ (2003)

Editor—Life is all that matters to me.1 I would not like it shortened even by a second. As a medical student, I have seen people who said brave things about dignity, but when the moment has come, they changed their minds—they didn't want to die. Neither do I.

I am willing to suffer. I know what pain is. Please, dear doctors, do not take these painful moments of life from me. Do anything you can. Do prolong my life. It may be painful, but it is all I have.
Topical Nitroglycerin for Ischemic Heart Disease
Authors: James A. Miner
Journal: JAMA (1978)

THE MAINSTAY of medical management of angina pectoris continues to be β-blocking agents and nitrates. Used initially in the treatment of Raynaud's disease,<sup>1</sup>nitroglycerin ointment was first introduced for the treatment of angina pectoris in 1955, but at that time it did not receive widespread clinical application. In the past few years, topical nitroglycerin has enjoyed a revival as a therapeutic agent, especially for patients with unstable or nocturnal angina. We compared the physiological and clinical effectiveness of sublingual and topical nitroglycerin (Nitrol Ointment) when used in patients with ischemic heart disease. <h3>Mechanism of Action of Nitroglycerin</h3> Myocardial ischemia is the result of an imbalance between myocardial oxygen demand and myocardial oxygen supply. Although nitroglycerin has been shown to be clinically effective in the therapy of this condition, its exact mechanism of action is still uncertain. At the present time it seems prudent to consider that nitroglycerin alters the
Abstract 10453: Increased Visceral Fat Area and Lower High-Molecular-Weight Adiponectin Level Predict Non-calcified Coronary Plaque Vulnerability in the Middle-aged Men, Using Computed Tomographic Angiography
Authors: Eiji Kunita, Hideya Yamamoto, Hiroto Utsunomiya, Toshiharu Oka, Ryo Yamazato, Yoji Urabe, Ken Ishibashi, Takenori Okada, Tomoki Shokawa, Satoshi Kurisu, Yukiko Nakano, Takafumi Ishida, Yasuki Kihara
Journal: Circulation (2010)

Background: Visceral fat accumulation has been a risk factor for coronary artery disease, and has decreased plasma high-molecular-weight adiponectin (HMW-AN) secreted from visceral adipose tissue. ...