tbuckley/cabot-search huggingface dataset:
Relation Among Stenosis Severity, Myocardial Blood Flow, and Flow Reserve in Patients With Coronary Artery Disease
Authors: Marcelo Di Carli, Johannes Czernin, Carl K. Hoh, Victor H. Gerbaudo, Richard C. Brunken, Sung-Chen Huang, Michael E. Phelps, Heinrich R. Schelbert
Journal: Circulation (1995)

Background Coronary arteriography is considered the “gold standard” for evaluating the severity of a coronary stenosis. Because the resistance to blood flow through a stenotic lesion depends on a number of lesion characteristics, the physiological significance of coronary lesions of intermediate severity is often difficult to determine from angiography alone. This study of patients with coronary artery disease seeks to determine the relation between myocardial blood flow and flow reserve measured by positron emission tomography (PET) and the percent area stenosis on quantitative coronary arteriography. Methods and Results We studied 28 subjects: 18 patients with coronary artery disease (66±8 years) and 10 age-matched healthy volunteers (64±13 years) with dynamic N-13 ammonia PET imaging at rest and after dipyridamole (0.56 mg/kg). The percent cross-sectional area stenosis was quantified on the coronary arteriograms as described by Brown et al. In the 18 patients, a total of 41 non–infarct-related coronary vessels were analyzed. Myocardial blood flows in normal regions of patients with coronary artery disease were not different than those in healthy volunteers, both at rest and after dipyridamole. As a result, the myocardial flow reserve was also similar in both groups (2.4±0.4 versus 2.6±0.7, respectively; P =NS). Quantitative PET estimates of hyperemic blood flow ( r =.81, P &lt;.00001), flow reserve ( r =.78, P &lt;.00001), and an index of the “minimal coronary resistance” ( r =.78, P &lt;.00001) were inversely and nonlinearly correlated with the percent area stenosis on angiography. Of note, PET estimates of myocardial flow reserve successfully differentiated coronary lesions of intermediate severity (50% to 70% and 70% to 90%; 2.4±0.4 versus 1.8±0.5, respectively; P =.04). Conclusions In patients with coronary artery disease, noninvasive measurements of myocardial blood flow and flow reserve by PET are inversely and nonlinearly related to stenosis severity as defined by quantitative angiography. Importantly, coronary lesions of intermediate severity have a differential flow reserve that decreases as stenosis increases that can be detected noninvasively by PET, thus allowing better definition of the functional importance of known coronary stenosis.
Names or Numbers?
Authors: Mario Stefanini
Journal: JAMA (1962)

ABSTRACT To the Editor:— Perhaps at no time since Morawitz have the hypotheses of blood coagulation process advanced by individual investigators been in such fairly good agreement as they appear to be today. The distinction between intrinsic and extrinsic mechanisms of blood clotting has clarified the role of some of the coagulation factors and has helped to place into proper perspective the relationship of the blood coagulation process to the intravascular formation of a thrombus. A certain degree of confusion remains, however, with the multiplicity of definitions applied to single clotting factors.For the past few years, an international committee for a unified system of nomenclature has recommended identifying clotting factors with Roman numerals, and identifying platelet factors with Arabic numerals. In principle, such an agreement would answer a real necessity. As any other classification, however, the one proposed is admittedly tentative, since most clotting agents are identified poorly with respect
Treatment of Lymphedema-Reply
Authors: David I. Abramson
Journal: JAMA (1979)

<h3>In Reply.—</h3> In general, I have no real quarrel with the treatment program for chronic lymphedema as outlined by Dr Lewis in his letter. However, I have never found an elastic pressure garment, even one that is custommade and includes a gradient of pressure, to be effective enough to compress the tissues of a lymphedematous limb to the point that swelling is prevented from accumulating during a day of physical activity that includes prolonged periods of standing. Nor are pressure bandages of any use in this regard. To control lymphedema a much higher topical pressure is required, and this is supplied by the application of a pure 100% pararubber bandage, as mentioned in my reply to Dr Hershey's question. Surgical therapy for chronic lymphedema has only limited clinical application. As Dr Lewis mentions, a large number of approaches have been proposed, but, in my opinion, the resulting therapeutic and cosmetic
Vanilloid Receptor-1 Regulates Neurogenic Inflammation in Colon and Protects Mice from Colon Cancer
Authors: Amaya G. Vinuesa, Rocío Sancho, Carmen García-Limones, Axel Behrens, Peter ten Dijke, Marco A. Calzado, Eduardo Muñoz
Journal: Cancer Research (2012)

Neuroinflammation driven by the vanilloid-type ion channel receptor transient receptor potential vanilloid type 1 (TRPV-1) is suspected to play a role in the pathophysiology of inflammatory bowel disease. Because inflammatory bowel disease is known to elevate the risk of colon cancer, we examined postulated roles for TRPV-1-driven neuroinflammation in promoting colitis-associated and spontaneous colon cancer development. Using a well-established model of colitis-associated cancer (CAC), we found that mice genetically deficient in TRPV-1 showed a higher incidence and number of tumors in the distal colon. In like manner, genetic deficiency of TRPV-1 in the APC(Min/+) model of spontaneous colon cancer accentuated the number of colonic adenomas formed. Mechanistic analyses in the CAC model revealed an increased infiltration of inflammatory cells into the tumors along with elevated expression of interleukin (IL)-6 and IL-11 and activation of the STAT3 and NF-κB signaling pathways. Notably, TPRV-1-deficient mice exhibited a defect in expression of the anti-inflammatory neuropeptides, vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP) which contributed to the generation of a local proinflammatory environment. Together, our findings argue that by limiting neuroinflammatory processes, TRPV-1 exerts a protective role that restricts the initiation and progression of colon cancer.
Monitoring enzyme replacement treatment in exocrine pancreatic insufficiency using the cholesteryl octanoate breath test.
Authors: S Mundlos, P Kuhnelt, G Adler
Journal: Gut (1990)

The cholesteryl-14C-octanoate breath test was used to monitor the intraluminal enzymatic activity of pancreatin preparations in six patients with severe pancreatic insufficiency. Conventional enzyme replacement, with cimetidine as an adjunct, was compared to supplementation with enteric coated microspheres. In healthy control subjects, 14CO2 excretion rose rapidly and peaked at 90-120 minutes; mean (SD) cumulative recovery at four hours was 51 (8)%. In patients with pancreatic insufficiency on no treatment mean (SD) cumulative recovery was only 6 (4)%. After pancreatin, with previous administration of cimetidine, it increased to 27 (11)% with a time course resembling that in controls. With 2 mm enteric coated microspheres, 14CO2 excretion did not rise significantly before 120 minutes and cumulative recovery after four hours was 15 (11)%. In a control study, 2 mm radio-opaque microspheres did not empty from the stomach until two hours after ingestion. The results suggest that the cholesteryl octanoate breath test can be successfully used to monitor the intraluminal enzymatic activity after treatment with different forms of enzyme replacement in pancreatic insufficiency. In contrast to treatment with conventional pancreatin and cimetidine as an adjunct, 2 mm enteric coated microspheres did not show in vivo enzymatic activity until two hours after administration.
Inhibition of hepatocellular carcinoma growth using immunoliposomes for co-delivery of adriamycin and ribonucleotide reductase M2 siRNA
Authors: Jie Gao, Huaiwen Chen, Yongsheng Yu, Jinjing Song, Hao Song, Xiao Su, Wei Li, Xin Tong, Weizhu Qian, Hao Wang, Jianxin Dai, Yajun Guo
Journal: Biomaterials (2013)
A comparison of effects of triamcinolone acetonide aqueous nasal spray, oral prednisone, and placebo on adrenocortical function in male patients with allergic rhinitis
Authors: W HOWLANDIII, R DOCKHORN, S GILLMAN, G GROSS, D HILLE, B SIMPSON, J FURST, G FEISS, J SMITH
Journal: Journal of Allergy and Clinical Immunology (1996)
Noggin Improves Bone Healing Elicited by Muscle Stem Cells Expressing Inducible BMP4
Authors: Hairong Peng, Arvydas Usas, Dave Hannallah, Anne Olshanski, Gregory M. Cooper, Johnny Huard
Journal: Molecular Therapy (2005)

The aim of this study was to test the hypothesis that a specific antagonist may enhance the efficacy of its corresponding growth factor in a regulated tissue engineering strategy. Our prior research has led to the development of a retroviral vector that enables optimal regulated bone morphogenetic protein 4 (BMP4) expression in vitro and regulated bone formation in vivo with transduced muscle stem cells. However, when implanted in critical-sized calvarial defects, these cells led to residual bone formation without induction or bone overgrowth with induction, even at reduced cell doses. We thus coimplanted the aforementioned cells with stem cells engineered to express Noggin, a specific BMP antagonist. This approach, while preserving our ability to regulate bone regeneration closely, prevented both the basal level bone regeneration and the bone overgrowth and, more importantly, led to the regeneration of bone that more closely resembled normal bone. We believe that this regulatable tissue engineering strategy, enhanced by utilizing a specific antagonist, constitutes a new paradigm for tissue engineering and regenerative medicine.
Chlorambucil-Prednisolone Therapy for Disseminated Breast Carcinoma
Authors: Herman A. Freckman, Harry L. Fry, Fernando L. Mendez, Elmer R. Maurer
Journal: JAMA (1964)

Over a 71/2-year period, 71 patients with disseminated breast cancer were treated with combined alkylating-agent-corticosteroid therapy. Chlorambucil and prednisolone were the drugs of choice. These agents, administered orally, produced no serious or disagreeable toxic effects. Twenty-four patients (33.8%) had objective regression of six months' duration or longer; average survival time after therapy was 23.9 months. Results are statistically similar to those obtained with sex-steroid and endocrine-ablation therapy, presumably because the three modalities have a similar mechanism of action, ie, suppression and/or eradication of endogenous estrogen.
Spinal and supraspinal modulation of visceral sensation
Authors: E A Mayer
Journal: Gut (2000)

In response to perceived or experienced change, which is considered threatening to the individual, the central nervous system mounts a stereotypic response which decreases the sensitivity to somatic pain, modulates autonomic nervous system outflow, and activates the hypothalamic-pituitary-adrenal axis. Recent experimental evidence obtained in rats suggests that this response can be associated with an increase in visceral sensitivity. This response of the “emotional motor system” may or may not be associated with the conscious experience of feelings of fear or anxiety. Alterations in some of these response systems (antinociception, vigilance) may be responsible for the characteristic visceral hypersensitivity often seen in patients with functional gastrointestinal disorders.

Irritable bowel syndrome (IBS) is a chronic disorder of unknown aetiology characterised by exacerbations and remissions, which presents with symptoms of abdominal pain and discomfort, and alterations in bowel habits. Approximately two thirds of patients report abdominal pain as one of their symptoms, and abdominal pain is reported by 40% of patients when asked for their most bothersome symptom.1The occurrence of certain stressful life events is the most important factor in symptom exacerbation and in the first development of symptoms.2-5 A recent prospective study emphasised that life events of a sustained duration, associated with threats to the patient's security, are most commonly associated with symptom exacerbation.2 In addition to these symptoms referred to the digestive system, clinical experience and recent reports in the literature have demonstrated a variety of extraintestinal symptoms in these patients, including other pain syndromes such as fibromyalgia (FM)6 7 and interstitial cystitis.8Furthermore, there is a close overlap between IBS and anxiety disorders.9 This article reviews evidence for the involvement of supraspinal pain modulation systems in the reported visceral hypersensitivity in IBS patients. For more information on the general topic of visceral hyperalgesia, …
RETINOBLASTOMA AND RECENT VIEWS OF MALIGNANCY
Authors: EDWARD JACKSON
Journal: JAMA (1926)

Observations with the microscope may furnish a good basis for the diagnosis and classification of tumors, when such observations furnish the most positive, characteristic and definite evidence that is obtainable. When the gross appearances, symptoms and clinical course of the case are more definite and distinct, they furnish a better basis for diagnosis than do the appearances revealed by the microscope. The best possible basis includes both microscopic and clinical evidence. A recent writer has pointed out that a need of our day is men who are both clinicians and pathologists, not mere clinicians on the one hand, or mere workers in the mortuary and laboratory on the other. The specializing process which leaves the pathologist ignorant of clinical medicine and the clinician ignorant of pathology has been harmful in many instances, but in none more harmful than in the case of malignant tumors arising in the retina. This disease
On Etymons and Hybrids
Authors: Lewis Thomas
Journal: New England Journal of Medicine (1974)

AN etymon is supposed to be a pure ore of a word, crystalline, absolutely original, signifying just what it was always intended to signify. They are very rare these days. Most of the words we use are hybrids, pieced together out of old, used speech by a process rather like the recycling of waste. We keep stores of discarded words around, out beyond the suburbs of our minds, stacked like scrap metal.When you do run across a primary, original word, the experience is both disturbing and vaguely pleasurable, like coming across a friend's picture in an old high-school annual. . . .
Iron-Overload–Related Disease in<i>HFE</i>Hereditary Hemochromatosis
Authors: Katrina J. Allen, Lyle C. Gurrin, Clare C. Constantine, Nicholas J. Osborne, Martin B. Delatycki, Amanda J. Nicoll, Christine E. McLaren, Melanie Bahlo, Amy E. Nisselle, Chris D. Vulpe, Gregory J. Anderson, Melissa C. Southey, Graham G. Giles, Dallas R. English, John L. Hopper, John K. Olynyk, Lawrie W. Powell, Dorota M. Gertig
Journal: New England Journal of Medicine (2008)

Most persons who are homozygous for C282Y, the HFE allele most commonly asssociated with hereditary hemochromatosis, have elevated levels of serum ferritin and transferrin saturation. Diseases related to iron overload develop in some C282Y homozygotes, but the extent of the risk is controversial.We assessed HFE mutations in 31,192 persons of northern European descent between the ages of 40 and 69 years who participated in the Melbourne Collaborative Cohort Study and were followed for an average of 12 years. In a random sample of 1438 subjects stratified according to HFE genotype, including all 203 C282Y homozygotes (of whom 108 were women and 95 were men), we obtained clinical and biochemical data, including two sets of iron measurements performed 12 years apart. Disease related to iron overload was defined as documented iron overload and one or more of the following conditions: cirrhosis, liver fibrosis, hepatocellular carcinoma, elevated aminotransferase levels, physician-diagnosed symptomatic hemochromatosis, and arthropathy of the second and third metacarpophalangeal joints.The proportion of C282Y homozygotes with documented iron-overload-related disease was 28.4% (95% confidence interval [CI], 18.8 to 40.2) for men and 1.2% (95% CI, 0.03 to 6.5) for women. Only one non-C282Y homozygote (a compound heterozygote) had documented iron-overload-related disease. Male C282Y homozygotes with a serum ferritin level of 1000 mug per liter or more were more likely to report fatigue, use of arthritis medicine, and a history of liver disease than were men who had the wild-type gene.In persons who are homozygous for the C282Y mutation, iron-overload-related disease developed in a substantial proportion of men but in a small proportion of women.
SAT0463 Incidence of Herpes Zoster Infections in Juvenile Idiopathic Arthritis Patients – Experience of the Biker Registry
Authors: G. Horneff, S. Nimmrich
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> An increased risk of herpes zoster among patients with juvenile idiopathic arthritis (JIA), especially with exposure to immunosuppressant medications and biologics have been described. <h3>Objectives</h3> We determined incidence rates of herpes zoster and medication among children with JIA. <h3>Methods</h3> Courses of treatments documented in the German Biologics Register (BiKeR) were analyzed to identify patients with herpes zoster and calculated crude infection rates (IR). Incidence ratio (IRR) was compared to published rates of 1.1/1000 person years(ref.). Demographics and exposure to corticosteroids, immunosuppressive drugs and biologics were analyzed. <h3>Results</h3> The JIA cohort included 3,042 patients with 5,407 person-years of follow-up; 1,628 have used corticosteroids, 2,930 have used methotrexate, 299 azathioprine, 192 cyclosportine A, 1685 etanercept, 299 adalimumab and 48 tocilizumab. In total 18 herpes zoster events have been documented (6/1000 patients [3.2-8.7]; 3.3/1000 patient years [2.1-5.3]). Thus the incidence rate was higher than expected (p&lt;0.001, IRR 2.97 [1.9-4.7]. In all patients the event resolved. One developed intercostal neuralgia. 1 had a recurrent herpes zoster. The occurrence of herpes zoster was significantly associated with the exposure to corticosteriods (100% of pts with zoster compared to 53% of who did not develop zoster; p&lt;0.0001) and the duration of exposure to methotrexate (70±56 months vs. 36±33 months; p&lt;0.01). There was no association to age or disease duration. Compared to patients exposed to methotrexate, the exposure to any of the biologics etanercept, adalimumab or tocilizumab seemed not to further increase the risk of zoster, while exposure to azathioprine did (table). <h3>Conclusions</h3> In JIA patients herpes zoster infection was found to be associated with treatment with corticosteroids and the duration of treatment with methotrexate. No association between treatment with biologics, etanercept, adalimumab or tocilizumab was found. <h3>References</h3> Insinga RP, <b>Itzler</b> RF, Pellissier JM, <b>Saddier</b> P, Nikas AA. The incidence of herpes zoster in a United States administrative database. J Gen Intern Med. 2005 Aug;20(8):748-53. <h3>Acknowledgements</h3> This study would not have been possible without the collaboration of numerous German and Austrian pediatric rheumatologists, patients and their parents. The German Registry is supported by Abbott, Pfizer (Wyeth Pharma) and Roche, Germany <h3>Disclosure of Interest</h3> G. Horneff Grant/research support from: Pfizer, Abbott, Roche, S. Nimmrich: None Declared
A New Role for the General Practitioner
Authors: Daniel Roth
Journal: JAMA (1966)

To the Editor:—  I should like to suggest a future role for the general practitioner in medicine.  The medical training of the future GP might be coordinated into a program leading to the PhD as well as the MD degree. Thus the generalist will enter medical practice with competence in the basic as well as the clinical sciences. While the specialties will always require specialized research capabilities, the broad range of the common diseases properly falls into the generalist's area. Nobody else is better equipped to know what the problems are, where the most need for research exists, and how useful the results of research become. The academician tends to cover his experimental results with a patina of theoretical significance and promise, but the generalist will know through clinical experience the practical merit of his investigations.  With the proper motivation and training, the generalist will be able to find the
Are placebo run ins justified?
Authors: S. Senn
Journal: BMJ (1997)

Every medical man commits that act of treachery, Mr Blake, in the course of his practice…. Every doctor in large practice finds himself, every now and then, obliged to deceive his patients. —Wilkie Collins, The Moonstone 

The placebo, it is agreed, is an excellent aid in determining the specific pharmacological effects of pharmaceutical agents. Any criticisms of placebos have usually been directed at the morality of giving an inert substance to patients hoping for effective treatment.1 2 Indeed, it might be argued that the object of drug development is to make the use of placebos unethical: to find a treatment that is so effective that it will be unacceptable to withhold it in the future. The debate has focused on acute conditions (especially if serious), where the ethical stakes are highest. For chronic conditions (especially if they are less severe) the situation is different. Here the patient may have to live with the condition for many years and, in his or her own interest, be prepared to try a number of treatments–including, from time to time, no treatment at all. With informed consent, the use of placebos in randomised clinical trials may then be uncontroversial.

It is often overlooked, however, that fully informed consent and a placebo can go together only if the clinical trial is randomised.3 Where this happens, the patient's doctor may say: “If you come on …
RELATIONSHIP OF MEDICINE WITH ALLIED HEALTH PROFESSIONS
Authors: Chauncey D. Leake
Journal: JAMA (1960)

<h3>To the Editor:—</h3> Wisely the American Medical Association is undertaking a systematic study of its relationships with allied health professions and services. An impressive committee is arranging for a series of conversations with officials of various organizations associated in the general health effort. These organizations include scientific groups representing experimental biology and the basic sciences for the health professions as well as various allied health professions. The number of these organizations is growing. They illustrate clearly the tremendous expansion of health services and activity. The A. M. A. Committee to Study the Relationship of Medicine with Allied Health Professions and Services is composed of members of the Board of Trustees, and representatives from the Council of Medical Education and Hospitals and the Council on Mental Health. Dr. Raymond M. McKeown is chairman, and Dr. John Hinman is secretary. The proceedings of the 1959 conferences have been issued in mimeographed form
Regression of Coronary Atheromatosis in Rhesus Monkeys
Authors: MARK L. ARMSTRONG, EMORY D. WARNER, WILLIAM E. CONNOR
Journal: Circulation Research (1970)

Rhesus monkeys subjected to the atherogenic stimulus of a high-fat, high-cholesterol diet showed significant coronary atheromatosis at the end of 17 months. Smaller fibrotic lesions with scant stainable lipid were found in animals that were subsequently fed either of two cholesterol-free diets for 40 months. The average cross-sectional area of the lumen was more than 80% greater in regression animals than in monkeys with baseline atherosclerosis. The data support the hypothesis that uncomplicated coronary atheromas may regress in primates in appropriate dietary settings.