tbuckley/cabot-search huggingface dataset:
Discovery of a new function of cyclooxygenase (COX)-2: COX-2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning
Authors: R Bolli
Journal: Cardiovascular Research (2002)

More than 10 years after its discovery, the function of cyclooxygenase-2 (COX-2) in the cardiovascular system remains largely an enigma. Many scholars have assumed that the allegedly detrimental effects of COX-2 in other systems (e.g. proinflammatory actions and tumorigenesis) signify a detrimental role of this protein in cardiovascular homeostasis as well. This view, however, is ill-founded. Recent studies have demonstrated that ischemic preconditioning (PC) upregulates the expression and activity of COX-2 in the heart, and that this increase in COX-2 activity mediates the protective effects of the late phase of PC against both myocardial stunning and myocardial infarction. An obligatory role of COX-2 has been observed in the setting of late PC induced not only by ischemia but also by δ-opioid agonists and physical exercise, supporting the view that the recruitment of this protein is a central mechanism whereby the heart protects itself from ischemia. The beneficial actions of COX-2 appear to be mediated by the synthesis of PGE2 and/or PGI2. Since inhibition of iNOS in preconditioned myocardium blocks COX-2 activity whereas inhibition of COX-2 does not affect iNOS activity, COX-2 appears to be downstream of iNOS in the protective pathway of late PC. The results of these studies challenge the widely accepted paradigm that views COX-2 activity as detrimental. The discovery that COX-2 plays an indispensable role in the anti-stunning and anti-infarct effects of late PC demonstrates that the recruitment of this protein is a fundamental mechanism whereby the heart adapts to stress, thereby revealing a novel, hitherto unappreciated cardioprotective function of COX-2. From a practical standpoint, the recognition that COX-2 is an obligatory co-mediator (together with iNOS) of the protection afforded by late PC has implications for the clinical use of COX-2 selective inhibitors as well as nonselective COX inhibitors. For example, the possibility that inhibition of COX-2 activity may augment myocardial cell death by obliterating the innate defensive response of the heart against ischemia/reperfusion injury needs to be considered and is the object of much current debate. Furthermore, the concept that the COX-2 byproducts, PGE2 and/or PGI2, play a necessary role in late PC provides a basis for novel therapeutic strategies designed to enhance the biosynthesis of these cytoprotective prostanoids in the ischemic myocardium. From a conceptual standpoint, the COX-2 hypothesis of late PC expands our understanding of the function of this enzyme in the cardiovascular system and impels a critical reassessment of current thinking regarding the biologic significance of COX-2.
Impotence: Diagnosis and Management of Male Erectile Dysfunction
Authors: Drogo K. Montague
Journal: JAMA (1993)

In the last 20 years there has been an enormous growth in the understanding, diagnosis, and treatment of male erectile dysfunction. Progress in this field has been so rapid that assembling knowledge into one text and presenting it in a timely fashion so that the material remains reasonably current is a major challenge. In spite of these difficulties, the editors of<i>Impotence: Diagnosis and Management of Male Erectile Dysfunction</i>have been largely successful. The text has a 1991 publication date, and references are reasonably complete through 1990. The book is well written and edited with chapters consistent in format and style, and there is little duplication of subject matter. The drawings are of good quality, but many of the photographs did not reproduce well. Detailed legends appear with all figures. Contributors to this text are recognized authorities and with two exceptions are from either the United Kingdom or the United
Intravascular Thrombosis After Hypoxia-Induced Pulmonary Hypertension
Authors: Graham P. Pidgeon, Rasa Tamosiuniene, Gang Chen, Irene Leonard, Orina Belton, Aidan Bradford, Desmond J. Fitzgerald
Journal: Circulation (2004)

Background— Pulmonary hypertension induced by chronic hypoxia is characterized by thickening of pulmonary artery walls, elevated pulmonary vascular resistance, and right-heart failure. Prostacyclin analogues reduce pulmonary pressures in this condition; raising the possibility that cycloxygenase-2 (COX-2) modulates the response of the pulmonary vasculature to hypoxia. Methods and Results— Sprague-Dawley rats in which pulmonary hypertension was induced by hypobaric hypoxia for 14 days were treated concurrently with the selective COX-2 inhibitor SC236 or vehicle. Mean pulmonary arterial pressure (mPAP) was elevated after hypoxia (28.1±3.2 versus 17.2±3.1 mm Hg; n=8, P &lt;0.01), with thickening of small pulmonary arteries and increased COX-2 expression and prostacyclin formation. Selective inhibition of COX-2 aggravated the increase in mPAP (42.8±5.9 mm Hg; n=8, P &lt;0.05), an effect that was attenuated by the thromboxane (TX) A 2 /prostaglandin endoperoxide receptor antagonist ifetroban. Urinary TXB 2 increased during hypoxia (5.9±0.9 versus 1.2±0.2 ng/mg creatinine; n=6, P &lt;0.01) and was further increased by COX-2 inhibition (8.5±0.7 ng/mg creatinine; n=6, P &lt; 0.05). In contrast, urinary excretion of the prostacyclin metabolite 6-ketoprostaglandin F 1α decreased with COX-2 inhibition (8.6±3.0 versus 27.0±4.8 ng/mg creatinine; n=6, P &lt; 0.05). Platelet activation was enhanced after chronic hypoxia. COX-2 inhibition further reduced the PFA-100 closure time and enhanced platelet deposition in the smaller pulmonary arteries, effects that were attenuated by ifetroban. Mice with targeted disruption of the COX-2 gene exposed to chronic hypoxia had exacerbated right ventricular end-systolic pressure, whereas targeted disruption of COX-1 had no effect. Conclusions— COX-2 expression is increased and regulates platelet activity and intravascular thrombosis in hypoxia-induced pulmonary hypertension.
Thermal Thresholds Predict Painfulness of Diabetic Neuropathies
Authors: Heidrun H. Krämer, Roman Rolke, Andreas Bickel, Frank Birklein
Journal: Diabetes Care (2004)

OBJECTIVE—Pathophysiology explaining pain in diabetic neuropathy (DN) is still unknown. RESEARCH DESIGN AND METHODS—Thirty patients with peripheral DN (17 men and 13 women; mean age 52.4 ± 2.5 years) were investigated. Fifteen patients had neuropathic pain, and 15 patients were free of pain. Patients were followed over 2 years and examined at the beginning and thereafter every 6 months. Clinical severity and painfulness of the DN were assessed by the neuropathy impairment score and visual analog scales (VASs). Cold and warm perception thresholds as well as heat pain thresholds were obtained for evaluation of Aδ- and C-fibers. Nerve conduction velocities (NCVs) and vibratory thresholds were recorded for analysis of thickly myelinated fibers. Moreover, for assessment of cardiac vagal function, heart rate variability (HRV) was evaluated. In order to reduce day-to-day variability of pain, mean values of the five time points over 2 years were calculated and used for further analysis. Data were compared with an age- and sex-matched control group of healthy volunteers. RESULTS—There were significant differences regarding electrophysiological studies, HRV and quantitative sensory testing (QST) between patients and healthy control subjects (P &amp;lt; 0.001). Generally, patients with neuropathic pain were indistinguishable from pain-free patients. In the pain group, however, VAS pain ratings were correlated to the impairment of small-fiber function (cold detection thresholds, P = 0.02; warm detection thresholds, P = 0.056). CONCLUSIONS—Intensity of pain in painful DN seems to depend on small nerve fiber damage and deafferentation.
Amelioration of severe psoriasis with psoriatic arthritis for 20 years after allogeneic haematopoietic stem cell transplantation
Authors: A C Woods
Journal: Annals of the Rheumatic Diseases (2006)

Haematopoietic stem cell transplantation (HSCT) is a recent potential treatment for severe autoimmune disease (AID).1 Few reports of results in severe psoriasis have been published.2,3,4,5,6,7,8,9,10 We report lasting benefit for 20 years after allogeneic HSCT in a patient with disabling psoriatic arthropathy.

A 29 year old man was admitted to hospital in 1985 with petechia. Extensive psoriasis had developed at age 13. In 1984, severe polyarthritis developed with swelling and tenderness of fingers, toes, and right heel. Range of motion was markedly decreased in shoulders and one hip. The right sacroiliac (SI) joint was tender. Radiography showed sclerosis of SI joints and partial fusion on the left. A bone scan showed increased uptake in many …
Ataxia-Telangiectasia With Gastric Adenocarcinoma
Authors: Armin F. Haerer
Journal: JAMA (1969)

This communication concerns a large Negro sibship of which five of 12 members had ataxia-telangiectasia. Two affected sisters also had mucinous adenocarcinoma of the stomach in the second decade of life. More detailed studies in one member revealed decreased IgA levels, decreased lymphoblastic transformation index, chromosomal abnormalities, and abnormal thymic and lymphoid tissues, in addition to the typical clinical features of this syndrome. The accepted predisposition to development of lymphoid neoplasms in ataxia-telangiectasia must be extended to include other malignant neoplasms, in view of the occurrence of histologically similar gastric adenocarcinomas in two affected siblings.
Bone Scan Appearance of Diastasis Pubis in Association with Congenital Extrophy of the Bladder
Authors: HO JEN, KEVIN TRACEY, ZOLLY CATZ, ALEXANDER McEWAN
Journal: Clinical Nuclear Medicine (1992)

Tc-99m MDP bone imaging demonstrated wide separation of the symphysis pubis and lateral displacement of the pubic bones in a 56-year-old woman with known congenital extrophy of the bladder. This appearance is typical of diastasis pubis and suggests a characteristic scintigraphic pattern. The radiologic appearance has previously been fully described.
Trends in deliberate self poisoning and self injury in Oxford, 1976-90.
Authors: K. Hawton, J. Fagg
Journal: BMJ (1992)

OBJECTIVE--To review trends in deliberate self poisoning and self injury (attempted suicide) over 15 years (1976-90) on the basis of general hospital referrals. DESIGN--Prospective data collection by computerised monitoring system. SETTING--Teaching general hospital. SUBJECTS--All patients aged 15 and over (n = 9605) referred to the hospital after episodes (n = 13,340) of deliberate self poisoning or self injury. MAIN OUTCOME MEASURES--Rates based on population of Oxford city; changes in substances used for self poisoning; history and repetition of attempts; and rates of admission to the hospital and of referral to the psychiatric service. RESULTS--Attempted suicide rates for women declined during the late 1970s and early 1980s but increased again during the late 1980s. Those for men remained relatively steady throughout the period. Highest mean annual rates occurred in women aged 15-19 (711/100,000) and in 20-34 year old men (334/100,000). The proportion of overdoses with paracetamol increased from 14.3% (125/873) in 1976 to 42% (365/869) in 1990 (chi 2 for trend = 481, p less than 0.01). Throughout the period the proportions of referred patients admitted to hospital and of those attempting suicide for the first time (over two thirds) did not decrease. Annual rates of repetition of attempts by women declined from 15.1% (257/1700) in 1976-8 to 11.9% (161/1356) in 1987-9 (chi 2 for trend = 7.8, p less than 0.01). Lower repetition rates occurred in women admitted to hospital and referred to the psychiatric service (431/4585, 9.4%) than in those not referred (42/235, 17.9%; chi 2 = 17.2, p less than 0.0001). CONCLUSIONS--Rates of attempted suicide declined in the 1970s and early 1980s, in women, but there are probably at least 100,000 hospital referrals a year in England and Wales because of this problem. Prevention of paracetamol self poisoning requires urgent attention, and psychosocial assessment should be conducted with as many of those who attempt suicide as possible.
Limited usefulness of exercise testing and thallium scintigraphy in evaluation of ambulator patients several months after recovery from an acute coronary event: Implications for management of stable coronary heart disease
Authors: Ronald J. Krone, John J. Gregory, Kenneth E. Freedland, Robert E. Kleiger, Frans J.Th. Wackers, Monty M. Bodenheimer, Jesaia Benhorin, Ronald G. Schwartz, John O. Parker, Lucy van Voorhees, Arthur J. Moss
Journal: Journal of the American College of Cardiology (1994)
TCT-664 Seven-year Clinical Outcomes of Sirolimus-Eluting Stent Versus Bare-Metal Stent; A Matched Analysis From A Real World, Single Center Registry
Authors: Jin-Sung Lee, Yoon-Jung Choi, Ung Kim, Jong-Seon Park, Jang-Won Son, Sang-Hee Lee, Dong-Gu Shin, Young-Jo Kim
Journal: Journal of the American College of Cardiology (2012)
Heat Shock Protein 90 Inhibitors: New Mode of Therapy to Overcome Endocrine Resistance
Authors: Cynthie Wong, Shiuan Chen
Journal: Cancer Research (2009)

Abstract Aromatase inhibitors are important drugs to treat estrogen receptor α (ERα)–positive postmenopausal breast cancer patients. However, development of resistance to aromatase inhibitors has been observed. We examined whether the heat shock protein 90 (HSP90) inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) can inhibit the growth of aromatase inhibitor–resistant breast cancers and the mechanisms by which 17-DMAG affects proliferation. Aromatase inhibitor–responsive MCF-7aro and aromatase inhibitor–resistant LTEDaro breast epithelial cells were used in this study. We observed that 17-DMAG inhibited proliferation in both MCF-7aro and LTEDaro cells in a dose-dependent manner. 17-DMAG induced apoptosis and G2 cell cycle arrest in both cell lines. Although inhibition of HSP90 decreased the levels of ERα, the ERα transcriptional activity was not affected when cells were treated with 17-DMAG together with estradiol. Moreover, detailed mechanistic studies suggested that 17-DMAG inhibits cell growth via degradation of HSP90 client proteins AKT and HER2. Collectively, results from this study provide data to support that HSP90 inhibitors may be an effective therapy to treat aromatase inhibitor–resistant breast cancers and that improved efficacy can be achieved by combined use of a HSP90 inhibitor and an AKT inhibitor. [Cancer Res 2009;69(22):8670–7]
Neurally adjusted ventilatory assist decreases ventilator-induced lung injury and non-pulmonary organ dysfunction in rabbits with acute lung injury
Authors: Lukas Brander, Christer Sinderby, François Lecomte, Howard Leong-Poi, David Bell, Jennifer Beck, James N. Tsoporis, Rosanna Vaschetto, Marcus J. Schultz, Thomas G. Parker, Jesús Villar, Haibo Zhang, Arthur S. Slutsky
Journal: Intensive Care Medicine (2009)
Comparative studies of atrial and ventricular myosin from normal, thyrotoxic, and thyroidectomized rabbits.
Authors: S K Banerjee
Journal: Circulation Research (1983)

Changes in enzymatic and structural properties of ventricular myosin in thyrotoxic rabbit hearts have been investigated extensively. However, there is little information regarding the effect of thyroid hormone on the atrial myosin. In this study, we have compared enzymatic and structural changes of ventricular and atrial myosin from euthyroid, hypothyroid, and hyperthyroid rabbits. In euthyroid rabbits, Ca++- and actin-activated ATPase activities of atrial myosin were 2-fold greater than those of the ventricular myosin. The Ca++- and actin-activated ATPase activities of atrial myosin from hypothyroid and hyperthyroid rabbits were identical with the values for atrial myosin from euthyroid rabbits. The same ATPase activities of ventricular myosin decreased in hypothyroid hearts but increased in hyperthyroid rabbits. The K+ (EDTA)-ATPase activities of all myosins were the same, irrespective of the thyroid status of the animal. Pyrophosphate-polyacrylamide gel electrophoresis patterns showed two isoenzymes (designated as A1 and A3) of atrial myosin in euthyroid hearts. The same electrophoretic patterns also showed in atrial myosin from hypothyroid and hyperthyroid hearts. The ventricular myosin from euthyroid hearts also exhibited two isoenzymes (designated as V1 and V3) but each with slower electrophoretic mobilities than the corresponding atrial myosin. In hypothyroid hearts, only V3 isoenzyme was seen, whereas, in hyperthyroid hearts, only V1 isoenzyme was seen. These results suggest that thyroid hormone controls ventricular myosin ATPase activity by controlling synthesis of a specific ventricular isoenzyme, whereas thyroid hormone does not affect atrial myosin ATPase, possibly due to its inability to control atrial myosin synthesis.
INFANTILE SCURVY IN WHICH SWOLLEN JOINTS RESEMBLED ACUTE ARTICULAR RHEUMATISM
Authors: Louis Fischer
Journal: JAMA (1913)

The importance of selecting the proper food for an infant prompts me to demonstrate this case, which I shall term faulty feeding. It is caused by feeding canned foods in which the antiscorbutic factor is wanting. Human breast-milk is a live food which is decidedly antiscorbutic; therefore no infant fed on the human breast acquires scurvy. If we would imitate Nature we must feed cow's milk in such a manner that it is not deprived of its enzymes. Boiling or prolonged steaming devitalizes the milk and is prone, if long continued, to develop scurvy. Canned or preserved milk is responsible for the damage done in the case reported. The patient, Joe W., aged 13 months, was seen by me in consultation with Dr. S. Barbash at Atlantic City, Oct. 11, 1912. The infant was bottle-fed from birth. He was given condensed milk the first month and later received malted milk
Randomised surgical trials need good surgical outcomes in the control arm
Authors: D. E. Neal, N. C. Shah, V. J. Gnanpragasam, V. Pati
Journal: BMJ (2011)

Crescenti and colleagues showed a significant reduction in transfusion requirements after administration of tranexamic acid to men undergoing open radical prostatectomy.1 However, at 55%, the rate of transfusion in …
Resveratrol improves intrahepatic endothelial dysfunction and reduces hepatic fibrosis and portal pressure in cirrhotic rats
Authors: Marco Di Pascoli, Marta Diví, Aina Rodríguez-Vilarrupla, Eugenio Rosado, Jorge Gracia-Sancho, Marina Vilaseca, Jaume Bosch, Joan Carles García-Pagán
Journal: Journal of Hepatology (2012)
Positive inotropism and myocardial energetics: influence of receptor agonist stimulation, phosphodiesterase inhibition, and ouabain
Authors: C. Holubarsch, G. Hasenfuss, H. Just, N. R Alpert
Journal: Cardiovascular Research (1994)

The aim was to study the effect of three positive inotropic interventions on myocardial force development and heat production in guinea pig papillary muscles in order to investigate the energetic consequences.The positive inotropic agents used were epinine (beta adrenoceptor stimulation), E-1020 (phosphodiesterase inhibition), and ouabain (sodium-potassium ATPase inhibition). Heat measurements were accomplished using antimony-bismuth thermopiles, and initial heat was separated into tension dependent and tension independent heat using the butanedione-monoxime (BDM) and the shortening methods.Optimal concentrations of epinine, E-1020, and ouabain increased peak developed force from 20.0(SD 6.6) to 55.5(9.3) (n = 5; p < 0.01), from 20.9(9.1) to 27.2(7.2) (n = 6; p < 0.05), and from 23.4(9.2) to 44.9(18.0) mN.mm-2 (n = 6; p < 0.01), respectively. Epinine and E-1020 decreased the tension-time integral per unit initial heat, ie, the economy of isometric contraction, from 5.5(1.4) to 3.6(0.5) (p < 0.01) and from 5.5(1.4) to 3.1(0.9) N.m.s.J-1 (p < 0.01), respectively; no significant change was observed with ouabain [6.7(1.4) to 8.3(0.5) N.m.s.J-1]. The tension independent heat (calcium turnover) was measured in two different ways using BDM or shortening to abolish force production. It was increased significantly by epinine (by 141-243%), E-1020 (by 77-114%), and ouabain (by 23-38%). The first measurement in brackets is the BDM estimate, the second is the shortening estimate. From the tension-time integral and the tension dependent heat the crossbridge force-time integral was analysed: epinine and E-1020 decreased the crossbridge force-time integral from 0.46(0.16) to 0.31(0.06) pN.s (p < 0.01) and from 0.50(0.19) to 0.31(0.08) pN.s (p < 0.01), respectively, while ouabain left the force-time integral unchanged [0.59(0.27) to 0.63(0.20) pN.s].(1) The inotropic effect of ouabain results from an increase in muscle activation with no change in crossbridge kinetics; (2) epinine and E-1020 increase the tension independent heat and decrease the crossbridge force-time integral, both effects reducing the overall economy; and (3) the shortening and BDM methods for measuring the tension independent heat give qualitatively similar but quantitatively different results.
Anterior Uveitis and Ankylosing Spondylitis
Authors: William Lipsky
Journal: JAMA (1978)

To the Editor.—  Calin et al (237:2613-2614, 1977) presented a most interesting observation that a clinical history alone may be sensitive and specific in the differential diagnosis of ankylosing spondylitis. However,. in view of the demonstrated association of acute anterior uveitis in 20% to 50% of patients with ankylosing spondylitis,1-3the questionnaire in Table 1 (p 2613) would have been more valuable and specific if it had asked questions such as the following: Have you had or have you ever been treated for an inflammation of the eyes? Have you ever been told by an eye doctor that there is evidence of an old inflammation in one or both eyes? Have you ever had an acute attack of abnormal sensitivity to light that required treatment?  As a practicing ophthalmologist, I am aware of the connection between anterior uveitis and ankylosing spondylitis and feel that the inclusion of these few
On the Treatment of Paroxysmal Dyspn a Occurring in Aneurysm of the Arch of the Aorta
Authors: H. F. A. Goodridge
Journal: BMJ (1887)

PROMPeT, energetic, but withal judicious, treatment can seldom be more imperatively required than 'in dealing with those formidable paroxysms of, suffocative dyspncea which are apt to auperYene in the progress of aneurysm of the aortic arch,,and which may even be the first intimation of the presence of that insidious disease.The too