tbuckley/cabot-search huggingface dataset:
Prodromal Symptoms in Myocardial Infarction
Authors: Fedra Ottolini, Maria Grazia Modena, Marco Rigatelli
Journal: Psychotherapy and Psychosomatics (2005)

Little is known about the prodromal phase of myocardial infarction (MI). The aim of this study was to explore this phase with methodologies which have been standardized in affective disorders. The psychological evaluation of patients with MI diagnosis is currently based on DSM-IV criteria. An alternative diagnostic and conceptual framework has been proposed by an international group of psychosomatic investigators. In this study, we are going to compare these new criteria, i.e. the Diagnostic Criteria for Psychosomatic Research (DCPR), with DSM-IV in a population where a high prevalence of psychological problems is expected.A semistructured research interview based on Paykel's Clinical Interview for Depression for eliciting prodromal symptoms was administered to a consecutive series of 92 patients with a first episode MI diagnosis. Two interviews for the evaluation of psychological problems were administered according to DSM-IV and DCPR criteria.Most of the patients reported prodromal symptoms. Irritability, depressed mood and somatic anxiety were the most common prodromal symptoms. The results also show that the number of DCPR diagnoses was higher than the number of DSM-IV diagnoses. At least one DCPR diagnosis was found in all patients, whereas at least one DSM-IV diagnosis was present in 42 (46%) patients.The prodromal phase of MI was found to be characterized by prodromal symptoms of affective type. The joint use of DSM-IV and DCPR criteria was found to improve the identification of psychological factors which could affect this phase. The results should alert the physician to the fact that patients presenting with irritability, depressed mood (including demoralization), anxiety and insomnia may be at risk of developing coronary artery disease.
An essential function for β-arrestin 2 in the inhibitory signaling of natural killer cells
Authors: Ming-Can Yu, Liu-Li Su, Lin Zou, Ye Liu, Na Wu, Ling Kong, Zi-Heng Zhuang, Lei Sun, Hai-Peng Liu, Jun-Hao Hu, Dangsheng Li, Jack L Strominger, Jing-Wu Zang, Gang Pei, Bao-Xue Ge
Journal: Nature Immunology (2008)
TOLERANCE TO FOREIGN BODIES WITHIN THE POSTERIOR SEGMENT OF THE EYE
Authors: ALBERT E. BULSON
Journal: JAMA (1926)

In 1882, Hermann Knapp<sup>1</sup>made the statement that, though in the great majority of instances foreign bodies which penetrate into the interior of an eye entail its ruin and too frequently even that of its fellow, they occasionally are encountered situated harmlessly in every part of the globe. He gives a short history of twelve cases on record up to that time, in which foreign bodies have lain innocently in the retina without great or even any impairment of central vision. These are as follows: Von Graefe<sup>2</sup>reported three cases in which small pieces of metal penetrated the eye, reached the inner membranes, and remained on them, not encapsulated but free, causing hemorrhages and transient opacities of the vitreous. They left local destruction of the retina, and irregular choroidal pigmentation and a corresponding scotoma, but otherwise there were useful sight and no protracted irritation. In the fourth case,
Fifty years later: the disk goes to the prom
Authors: Mark E. Kleinman, Jayakrishna Ambati
Journal: Journal of Clinical Investigation (2008)

Although age-related macular degeneration is the most prevalent macular disease in the world, numerous discoveries regarding the molecular bases of vision have been made through genetic association studies of rare inherited maculopathies. In this issue of the JCI, Yang et al. present a functional genetics study that identifies a role for prominin 1 (PROM1), best known as a stem cell and/or progenitor cell marker, in the biogenesis of retinal photoreceptor disk arrays (see the related article beginning on page 2908). This study supports an established model in which disk morphogenesis occurs through membrane evagination and extends other recent studies assigning PROM1 important functions outside of the stem cell niche.
ACCURACY OF COMPUTED TOMOGRAPHY FOR DETECTION OF LEFT ATRIAL THROMBUS PRIOR TO CATHETER ABLATION OF ATRIAL FIBRILLATION
Authors: Sreedevi Gondi, Swarna Debbarma, Antonieta I. Hernandez, Jie Cheng, Benjamin Y. Cheong, Stephanie Coulter
Journal: Journal of the American College of Cardiology (2012)
437 THE LIVER STEATOSIS IN PRE-PUBERAL OBESE CHILDREN IS NOT RELATED TO THE RESISTANCE TO INSULIN
Authors: A. Ruiz Extremera, A. Carazo Gallego, A. Salmeron-Ruiz, J. Casado, J. León, J.M. Fernandez, M. Garofano, E. Ocete, A. Gila, L. Sanjuan, J. Salmerón
Journal: Journal of Hepatology (2009)
Should we screen for type 2 diabetes? No
Authors: E. Goyder, L. Irwig, N. Payne
Journal: BMJ (2012)

<b>Kamlesh Khunti</b> and <b>Melanie Davies </b>(doi:10.1136/bmj.e4514) believe that screening for diabetes is feasible and cost effective, but <b>Elizabeth Goyer and colleagues</b> think that a population approach to modifying risk factors would be better
Homocystinuria due to cystathionine synthase deficiency: the effect of pyridoxine
Authors: S. Harvey Mudd, William A. Edwards, Peter M. Loeb, Michael S. Brown, Leonard Laster
Journal: Journal of Clinical Investigation (1970)

We investigated the effect of pyridoxine administration in three patients with homocystinuria due to cystathionine synthase deficiency. The drug decreased the plasma concentration and urinary excretion of methionine and homocystine and the urinary excretion of homolanthionine and the homocysteine-cysteine mixed disulfide. Urinary cystine rose somewhat. Oral methionine tolerance tests before and during the patients' response to pyridoxine indicated that during response they remained deficient in their capacity to convert the sulfur of methionine to inorganic sulfate, although this capacity increased somewhat. During pyridoxine response only, the methionine loads caused increased homocystinuria. There was no indication that pyridoxine stimulated an alternate pathway of metabolism. The values for specific activity of cystathionine synthase in liver biopsy specimens from two patients in pyridoxine response were 3 and 4% of the mean control value. When these patients were not receiving pyridoxine, comparable values were 2 and 1%, respectively. The hepatic enzyme activity of the mutant patients was similar to normal enzyme activity with respect to trypsin activation, heat inactivation, and stabilization by pyridoxal phosphate. Approximate estimates were made of the relation between total body capacity to metabolize methionine and hepatic cystathionine synthase activity. These estimates suggested that because of the large normal reserve capacity of cystathionine synthase, a few per cent residual activity is sufficient to metabolize the normal dietary load of methionine. Thus, small increases in residual capacity may be of major physiological importance. However, many liver biopsies would be required to establish unequivocally that such changes were due to the administration of a particular therapeutic agent rather than to biological variation. All the data in the present study are consistent with the interpretation that pyridoxine does act by causing an increase in residual cystathionine synthase activity.
Abnormalities of Renal Function and Circulatory Reflexes in Primary Aldosteronism
Authors: EDWARD G. BIGLIERI, MALCOLM B. MCILROY
Journal: Circulation (1966)

The renal response to intravenous administration of isotonic saline solution and circulatory reflex reactivity was studied in nine patients with primary aldosteronism before and after surgical removal of an adrenal adenoma. In preoperative tests, infusion of saline was followed by abnormally rapid renal excretion of sodium and water, such as occurs in patients with autonomic insufficiency. Circulatory reflex function was also abnormal in all patients; the most severe impairment was shown by two patients with hypokalemia and weakness of long duration. Postoperatively, both renal and circulatory reflex responses returned to normal or near normal. In preoperative tests on three patients, potassium repletion effected a similar correction of both renal and circulatory reflex abnormalities. The cause of these abnormalities in patients with primary aldosteronism is not known. Potassium depletion may be a factor, although a general disturbance of autonomic cardiovascular function cannot be excluded.
The effects of catecholamine and related compounds on the adenyl cyclase system in the epidermis*
Authors: KUNIHIKO YOSHIKAWA, KENJI ADACHI, KENNETH M. HALPRIN, VICTOR LEVINE
Journal: British Journal of Dermatology (1975)

The effect of various hormones and drugs on the adenyl cyclase system of pig and human epidermal slices was studied in vitro. Adrenaline and isoproterenol in the presence of theophylline increased the epidermal cyclic AMP level 20-fold in 5 min. Noradrenaline also stimulated cyclic AMP accumulation but to a much lesser degree. The adrenaline stimulation was marked even in the absence of the phosphodiesterase inhibitor, theophylline. Theophylline potentiated the effect of adrenaline at the concentration of 2-10 mM although theophylline alone did not elevate the cyclic AMP level significantly. The Km for adrenaline stimulation of the adenyl cyclase system of pig epidermis was 7-7 X 10(-7) M. A beta-adrenergic antagonist, propranolol, markedly inhibited the adrenaline stimulation while alpha-antagonists, phentolamine or priscoline, showed little effect. The results are in accord with the view that the epidermis possesses an active adenyl cyclase system with beta-adrenergic receptors.
Uptake of Tc-99m Sestamibi by Brown Tumors in a Patient with Primary Hyperparathyroidism
Authors: ANNAMALAI MUTHIAH, JIM G. KALANI, DOUGLAS S. KATZ
Journal: Clinical Nuclear Medicine (1998)

This article discusses a case of Tc-99m sestamibi uptake by brown tumors in a patient with primary hyperparathyroidism. Brown tumors are characteristic tumors of hyperparathyroidism and often have well-defined margins. In this patient with clinical findings of hyperparathyroidism, a retrosternal parathyroid adenoma was identified using Tc-99m sestamibi parathyroid scintigraphy. The adenoma was resected surgically, and the diagnosis was confirmed histopathologically.
Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS)
Authors: Cindy E. Neunert, George R. Buchanan, Paul Imbach, Paula H. B. Bolton-Maggs, Carolyn M. Bennett, Ellis Neufeld, Sara K. Vesely, Leah Adix, Victor S. Blanchette, Thomas Kühne
Journal: Blood (2013)
A Phase (Ph) I/II Study of CR011-VcMMAE, an Antibody-Drug Conjugate, in Patients (Pts) with Locally Advanced or Metastatic Breast Cancer (MBC).
Authors: H. Burris, H. Burris, M. Saleh, J. Bendell, J. Bendell, L. Hart, L. Hart, A. Rose, Z. Dong, P. Siegel, M. Crane, D. Donovan, E. Crowley, R. Simantov, L. Vahdat
Journal: Cancer Research (2009)

Abstract Background: Glycoprotein NMB (GPNMB), also known as osteoactivin, is expressed in 25-40% of breast cancers and is associated with an increased risk of recurrence. This is the first study of CR011-vcMMAE, a fully-human monoclonal anti-GPNMB antibody conjugated to the tubulin inhibitor monomethylauristatin E (MMAE), in pts with breast cancer.Methods: Eligible pts with MBC had ³ 2 prior chemotherapy regimens, including a taxane, an anthracycline, and capecitabine; and ECOG PS ≤ 2. Doses were escalated to 1.88 mg/kg IV q3w (the maximum tolerated dose [MTD] in a previous study of patients with melanoma) using a standard 3+3 design followed by a Ph II expansion at the MTD. Pts received CR011-vcMMAE until disease progression (PD) or intolerable toxicity. The primary endpoint of the Ph II study was 12-week progression free rate, defined as the proportion of patients who were alive and free of progressive disease 12 weeks from the first dose of CR011-vcMMAE. A Simon two-stage minimax design was used (p0=0.1; p1=0.3, α=β=0.1) with 16 patients in the first stage and a total of 25 pts. Secondary endpoints included objective response rate and duration of response. IHC with a goat polyclonal antibody to GPNMB was performed on pt biopsy specimens.Results: In Ph I, 14 pts were treated with CR011-vcMMAE at 1.0 mg/kg (n=3), 1.34 mg/kg (n=5), and 1.88 mg/kg (n=6). In the first 2 pts at 1.34 mg/kg, dose limiting toxicity of worsening peripheral sensory neuropathy was observed. Pts with baseline neuropathy worse than grade 1 were subsequently excluded. There were 3 partial responses, one confirmed, and 1.88 mg/kg q3w was selected for Ph II. In Ph II, 14 pts with MBC (median age 57 years, range 34 - 76) had a median of 5 prior regimens; median follow up was 6 weeks; 12 pts are ongoing (median duration 6 weeks, range 1 - 14 weeks). Two pts were progression-free at 12 weeks, therefore the study has met the criteria for advancement to the second stage. The most common AEs were rash (61%), fatigue (50%) and alopecia (50%). The most common grade 3/4 AEs were neutropenia (17%) and neuropathy (11%). IHC staining of 5 patient biopsies revealed 2 with positive GPNMB expression, including one of the patients with PR.Conclusions: CR011-vcMMAE is active and well-tolerated in heavily pretreated pts with advanced breast cancer. The Phase II study has met the criteria for advancement into the second stage, and enrollment is ongoing. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6096.
Can heart failure be diagnosed in primary care?
Authors: R. Hobbs
Journal: BMJ (2000)

Papers p 215 

Heart failure is an increasingly important problem for primary care physicians in most healthcare systems in developed countries. The condition is almost as common as diabetes mellitus in older adults, occurring in at least 2% of the adult population and rising to 3% in those aged over 75 years. 1 2 Although the incidence of most cardiovascular diseases has declined over the past 20 years, the incidence of heart failure has continued to rise, due in part to the fact that more people are surviving after acute myocardial infarctions and also to the increasing number of elderly people.3

Symptomatic heart failure has a major impact on patients and healthcare systems: it has a worse prognosis than breast cancer or prostate cancer and is second only to stroke in terms of healthcare costs.4 Heart failure costs the United States over $8bn (£5bn) each year, and 5% of all admissions in the United Kingdom involve some degree of heart failure.5 In addition to high mortality, patients with heart failure also have morbidity from symptoms such as dyspnoea and fatigue.6

Accurate and early diagnosis is important since angiotensin converting enzyme inhibitors improve both morbidity and mortality …
Multi-Arm Clinical Trials of New Agents: Some Design Considerations
Authors: Boris Freidlin, Edward L. Korn, Robert Gray, Alison Martin
Journal: Clinical Cancer Research (2008)

Abstract A major challenge in the development of anticancer therapies is the considerable time and resources needed for conducting randomized clinical trials (RCT). There is a need for more efficient RCT designs that accelerate development, minimize costs, and make trials more appealing to patients. We review the statistical and logistical characteristics of multi-arm designs that compare several experimental treatments to a common control arm. In particular, we present a rationale for not requiring multiplicity adjustment in multi-arm trials that are designed for logistical efficiency. Relative to conducting separate RCTs for each experimental agent, this multi-arm design is shown to require a lower total sample size than multiple two-arm trials.
LONG TERM IMPROVEMENT IN RENAL FUNCTION DURING CONTINUOUS FLOW LEFT VENTRICULAR ASSIST DEVICE SUPPORT IS ASSOCIATED WITH USAGE OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEIS) OR ANGIOTENSIN RECEPTOR BLOCKERS (ARBS)
Authors: Omar Saeed, Rita Jermyn, Snehal Patel, Jooyoung Shin, David D'lessandro, Daniel Goldstein, Ronald Zolty
Journal: Journal of the American College of Cardiology (2014)
Patients Selected for Definitive Concurrent Chemoradiation at High-volume Facilities Achieve Improved Survival in Stage III Non–Small-Cell Lung Cancer
Authors: Elyn H. Wang, Charles E. Rutter, Christopher D. Corso, Roy H. Decker, Lynn D. Wilson, Anthony W. Kim, James B. Yu, Henry S. Park
Journal: Journal of Thoracic Oncology (2015)
Cell-cell signaling between adult rat ventricular myocytes and cardiac microvascular endothelial cells in heterotypic primary culture.
Authors: M Nishida, J P Springhorn, R A Kelly, T W Smith
Journal: Journal of Clinical Investigation (1993)

It is unclear whether signaling between endothelial cells and muscle cells within ventricular myocardium, known to be important during cardiac development, remains physiologically relevant in the adult heart. Also, the mechanisms regulating the synthesis and activation of locally acting autacoids such as endothelins, cytokines known to have potent effects on contractile function and gene expression in cardiac myocytes, are unknown, as their cells of origin within ventricular muscle. Microvascular endothelial cells isolated from ventricular tissue of adult rats do not express endothelins constitutively. However, the appearance of preproendothelin mRNA can be increased in cardiac microvascular endothelial cells by heterotypic primary culture with adult rat ventricular myocytes. Cell-cell contact, or at least close apposition, appears to be necessary to increase preproendothelin mRNA, as medium conditioned by ventricular myocytes alone was ineffective when applied to monocultures of microvascular endothelial cells. The level of TGF beta precursor mRNA is also markedly increased in microvascular endothelial cells in coculture and precedes the appearance of endothelin precursor transcripts. In coculture, TGF beta acts as an autocrine cytokine, increasing endothelin precursor mRNA and inhibiting the rate of microvascular endothelial cell proliferation. This regulation of endothelial cell phenotype in heterotypic primary cultures suggests that dynamic, reciprocal cell-cell signaling may also be occurring between microvascular endothelium and ventricular myocytes in vivo.
Recovery of Urinary Continence after Radical Prostatectomy: Association with Urethral Length and Urethral Fibrosis Measured by Preoperative and Postoperative Endorectal Magnetic Resonance Imaging
Authors: Philippe Paparel, Oguz Akin, Jaspreet S. Sandhu, Javier Romero Otero, Angel M. Serio, Peter T. Scardino, Hedvig Hricak, Bertrand Guillonneau
Journal: European Urology (2008)
Medical education--preload and afterload
Authors: S. Vaisrub
Journal: JAMA (1978)

While the physician scans undecidedly the various continuing medical education (CME) programs for category 1 accreditation, his son or daughter may be similarly unsure about course selection for premedical studies. He or she, however, is sure of one decision—the major course will be a science. They believe that science is more relevant to their career, and they know that in the Medical College Admissions Test, the science part wields more clout. Should they decide to take a minor course in the humanities, they are likely to choose one that requires the least time and effort.  If ever support was needed for C. P. Snow's tenuous two-cultures thesis, the science bias of the premedical studies provides one. Ironically, it does it now when, more than ever, medicine demands from the physician the broadest possible intellectual scope to meet the complexities of the times.  In a recent Notes of a Biology-Watcher, Lewis
VO2 slow component and performance in endurance sports
Authors: Andrew Jones
Journal: British Journal of Sports Medicine (2000)

Editor,—I read with interest the leader by Veronique Billat entitled “Vo2 slow component and performance in endurance sports”.1 Oxygen uptake kinetics in general, and the aetiology of the Vo2 slow component phenomenon in particular, are certainly topics of great conceptual and practical importance. However, there were several points of contention within Dr Billat's article that should be brought to the attention of readers so that an informed and balanced debate can take place.

Dr Billat states that “A high range of work (rates) can be identified at which there is a sustained increase in blood lactate . . .with time. These responses decline back towards a baseline value.” These two sentences, which are applied to a description of the physiological responses to moderate intensity exercise, are clearly inconsistent. It is also stated that during moderate exercise “oxygen uptake stabilises at about 80% in high level marathon runners”. This suggests that Vo2 will reach a steady state close to 80% Vo2max irrespective of the absolute work rate within the moderate exercise intensity domain. However, it should be remembered that moderate intensity exercise is, by definition, any exercise that is performed below the lactate threshold. Therefore constant load moderate exercise can lead to the attainment of a steady …
Prognostic classification of malignant melanoma by clinical criteria
Authors: W. FUNK, CH. SCHMOECKEL, D. HOLZEL, O. BRAUN-FALCO
Journal: British Journal of Dermatology (1984)

In a retrospective study of 503 well-documented cases of primary malignant melanoma (stage I) clinical criteria were analysed for their prognostic relevance. The maximum elevation (in mm) of the tumour was found to be the most important single prognostic factor. There was a close association with tumour thickness, measured histologically by the method of Breslow (correlation coefficient = 0.73). A combination of elevation and three additional clinical criteria (site, nodule- or lesion-diameter, and surface defects such as erosion, ulceration or bleeding) allowed a further improvement in prognostic accuracy. This clinical classification into low-risk and high-risk melanomas was as effective as the use of tumour thickness measured histologically, and can therefore be used for the preoperative planning of treatment.