tbuckley/cabot-search huggingface dataset:
Selective Reduction of Serotonin Storage and ATP Release in Chronic Renal Failure Patient Platelets
Authors: Gerald Soslau, Janet Parker, Isadore Brodsky, Bhaben Putatunda, Allan B. Schwartz
Journal: American Journal of Hematology (1990)

Abstract Hemorrhagic complications, as monitored by skin bleeding times, occur in a significant number of chronic renal failure (CRF) patients. The etiology of hemostatic defects in these patients is complex and ill defined. Our studies demonstrate, for the first time, that activated platelets, derived from CRF patients, release significantly ( P &lt; 0.001) less ATP than controls while the percent of releasable serotonin (5HT), assumed to be co‐stored with ATP, is unaltered. Analysis of the CRF‐derived platelets reflects a selective acquired storage pool defect with significantly ( P &lt; 0.001) reduced 5HT levels while their dense granule contents of ATP and ADP are normal. The comparison of ATP release from platelets derived from CRF patients whose bleeding times were less than 9 min to those with bleeding times of 9 min or greater was significantly different ( P &lt; 0.02). This report demonstrates for the first time that there is a statistically significant correlation of ATP release and 5HT content to bleeding times ( P &lt; 0.001). The perturbation of platelet 5HT uptake, 5HT dense granule content, and ATP release appears to result from newly described altered plasma factors, detected by our in vitro mixing studies. It is proposed that the reduced level of releasable platelet 5HT and ATP contributes to bleeding disorders commonly encountered in CRF patients.
NEPHROSTOMY DRAINAGE AND SPLINTING OF URETER IN ROUTINE KIDNEY SURGERY
Authors: H. Haynes Baird
Journal: JAMA (1952)

There has been very little written on nephrostomy drainage and splinting of the ureter in routine kidney surgery except in connection with pyeloplasties and revision of the ureteropelvic junction. However, we believe that by applying the following two fundamental surgical principles, nephrostomy drainage and a ureteral splint will be more frequently used: 1. An infected kidney should be adequately drained. 2. Ureteral peristalsis is dependent on a histologically normal intact ureter and fluid within the lumen.  If one goes back many years prior to the advent of chemotherapy and antibiotics, one finds that it was not an infrequent occurrence for a urologist to do a nephrostomy or a pyelostomy in cases of severe pyelonephritis of pregnancy. For a long period of time nothing of importance was done about nephrostomy drainage until the advent of plastic surgery on the pelvis of the kidney and upper part of the ureter. In this
Re: On the Use of Familial Aggregation in Population-Based Case Probands for Calculating Penetrance
Authors: A. S. Whittemore, G. Gong
Journal: JNCI Journal of the National Cancer Institute (2003)

In a recent issue of the Journal (1), Begg describes potential biases in our (2) and other population-based casescreening studies that estimate mutation penetrance through kin-cohort methods (3).The main issue raised by Begg is that a case series represents individuals selected to have risk factors that place them at excess disease risk.To the extent that any risk factors are overrepresented among case relatives-because of either genetic or familial reasonsfamily members of both carrier and noncarrier probands will show excess disease incidence, and thus mutation penetrance will be overestimated.We agree with this theoretical argument but question the degree of bias actually present in the published studies of breast and ovarian cancer and mutations in BRCA1 or BRCA2 to which Begg refers (1).In particular, our penetrance estimates of breast cancer based on an ovarian cancer case series are unlikely to be biased (2).Disease risk to a given age among carrier and noncarrier relatives is found by treating the relatives as a cohort and performing a Cox regression analysis on it, with age at diagnosis, death, or end of follow-up as the time variable and with proband mutation status as the exposure.This method yields an estimate of the relative risk (RR) of disease among relatives associated with proband mutation status, as well as a product-limit estimate of the survivor function for the noncarrier relatives (S 0 ).The estimated mutation penetrance is 1 + S 0 -2(S 0 ) RR .This method is robust in the usual circumstances of one (or sometimes two) affected first-degree relatives per family, but generalized estimating equation methods can also be used.As Begg notes (1), the estimated RR is not subject to the bias; only S 0 is subject to bias.In fact, 1 + S 0 -2(S 0 ) RR estimates the penetrance for any similar base population to which the RR would apply.Therefore, for studies such as ours (2) that use this method, and in the very usual circumstances where mutation frequency is low in the population, the observed RR values can certainly be used
Should Large Cell Neuroendocrine Lung Carcinoma be Classified and Treated as a Small Cell Lung Cancer or with Other Large Cell Carcinomas?
Authors: John M. Varlotto, Laura Nyshel Medford-Davis, Abram Recht, John C. Flickinger, Eric Schaefer, Dani S. Zander, Malcolm M. DeCamp
Journal: Journal of Thoracic Oncology (2011)
Expression of Concern: Kiel et al. Efficacy of a hip protector to prevent hip fracture in nursing home residents: the HIP PRO randomized controlled trial. <i>JAMA</i>. 2007;298(4):413-422.
Authors: Howard Bauchner, Phil B. Fontanarosa
Journal: JAMA (2012)

Douglas P. Kiel, MD, MPH; Jay Magaziner, PhD; Sheryl Zimmerman, PhD; Linda Ball, PhD; Bruce A. Barton, PhD; Kathleen M. Brown, PhD; Judith P. Stone, MSW; Dawn Dewkett, BS; Stanley J. Birge, MD
Radiotherapy in the Management of Clinically Localized Prostate Cancer: Evolving Standards, Consensus, Controversies and New Directions
Authors: Joycelyn L. Speight, Mack Roach
Journal: Journal of Clinical Oncology (2005)

Major advances have been made in the definitive use of various forms of radiotherapy (RT) in the management of clinically localized prostate cancer (PCa). Despite tremendous gains, the radiation oncology community continues to struggle with several key questions. In general, the areas of controversy pertain to how to improve the therapeutic ratio of RT. Specifically, key issues include dose escalation; the relative benefit of alternative forms of RT (ie, brachytherapy and protons); target localization; the use, timing, and duration of androgen deprivation; and the need for pelvic nodal irradiation. Multiple efforts have been made to address each of these issues; however, there is no consensus on how to resolve them. This review is an evidence-based critique of the available treatment approaches considered for the optimal use of radiotherapy as definitive management of clinically localized PCa.
Guidelines for clinical guidelines should distinguish between national and local production
Authors: J G Williams
Journal: BMJ (1999)

EDITOR—Jackson and Feder put forward sensible arguments for pragmatic simplicity in clinical guidelines that should be reflected in similar simplicity in guidelines for guidelines.1However, they do not distinguish between guidelines produced by reputable national bodies and those that have been adapted from others for local use.

Nationally produced guidelines must be rigorously developed and …
Labelling of foodstuffs for patients with coeliac disease.
Authors: A E Pawan
Journal: BMJ (1977)

Miss Hunt and her colleagues have postulated that vitamin D and to a lesser extent outdoor exposure are the two most important factors in the determination of the vitamin D status of Asians.If this is so any difference in the serum 25-OHD3 levels of the five different religious groups should be explicable in terms of these two variables alone.Examination of the variation in serum 25-OHD3 when the concomitant variation in outdoor exposure and vitamin D intake had been taken into account in the model mentioned above revealed that a significant difference in the serum 25-OHD3 levels of the different religious groups still existed (F=9 7; 4,74 DF; P<0 001).On in- clusion of chapatty intake in the model, no such difference between religious groups was detectable (F=2 36; 4,73 DF; P>0 05).It would therefore seem essential to include chapatty in any model of vitamin D status in Asians.The amount of variation in serum 25-OHD3 explained by chapatty flour alone (23 040o = 100r2) is greater than the combined contributions of dietary vitamin D and out- door exposure (19-2"o).These findings strongly support earlier observations which have incriminated chapatty consumption in the aetiology of Asian rickets.35
The Saga of the Ring B Unsaturated Equine Estrogens*
Authors: BHAGU R. BHAVNANI
Journal: Endocrine Reviews (1988)

THE RING B unsaturated estrogens, equilin, equilenin, 17α-dihydroequilin, 17α-dihydroequilenin, 17β-dihydroequilin, and 17β-dihydroequilenin, are present in the urine of pregnant mares. Along with the ring B unsaturated estrogens, pregnant mare's urine also contains the classical estrogens, estrone, 17α-estradiol, and 17β-estradiol. The ring B unsaturated estrogens, as the name indicates, differ structurally from the classical estrogens by the presence of one or two additional double bonds in the ring B of the steroid nucleus (Fig. 1). The ring B unsaturated estrogens were first isolated by Girard et al. in 1932 (1, 2); however, their biosynthetic origin has not yet been fully elucidated. In 1941, a urinary extract containing the sulfate esters of the above nine estrogens was prepared from pregnant mare's urine by Ayerst Laboratories (Montreal, Quebec, Canada) and was named Premarin. This preparation has been for the last four decades, the most commonly prescribed estrogen for replacement therapy in estrogendeficient women. Recent epidemiological evidence suggests an etiological role for these estrogens in the carcinoma of the human endometrium. This review will discuss, 1) the existence of two pathways of steroidogenesis in the pregnant mare: (a) the classical pathway via cholesterol leading to the formation of the classical estrogens, estrone and estradiol, and (b) an alternate pathway which bypasses cholesterol and leads to the biosynthesis of ring B unsaturated estrogens, equilin and equilenin; 2) the biological activity of the ring B unsaturated estrogens; 3) the pharmacokinetics of equilin sulfate in postmenopausal women; 4) comparison of the interaction of ring B unsaturated estrogens and the classical estrogens with human endometrial estrogen receptors; 5) the role (if any) of ring B unsaturated estrogens in the etiology of endometrial cancer.
Comparative effects of aspirin, a synthetic thrombin inhibitor and a monoclonal antiplatelet glycoprotein IIb/IIIa antibody on coronary artery reperfusion, reocclusion and bleeding with recombinant tissue-type plasminogen activator in a canine preparation
Authors: Tsunehiro Yasuda, Herman K. Gold, Hiroyuki Yaoita, Robert C. Leinbach, J.Luis Guerrero, Ik-Kyung Jang, Robert Holt, John T. Fallon, Desire Collen
Journal: Journal of the American College of Cardiology (1990)
TCT-567 Long term Safety and Efficacy of Biodegradable Polymer-Coated Sirolimus-Eluting Stents in “Real-World” Practice: 5 year follow-up of the CREATE (multi-Center Registry of EXCEL Biodegradable Polymer Drug Eluting Stents) Study
Authors: Ya-Ling Han, Quan-Yu Zhang
Journal: Journal of the American College of Cardiology (2012)
Abstract 4306: NAD(P)H:quinone oxidoreductase 1 (NQO1) regulates MAPK activation and cellular protection against chemical stress.
Authors: Brad A. Patrick, Anil K. Jaiswal
Journal: Cancer Research (2013)

Abstract NAD(P)H: quinone oxidoreductase (NQO1) is a cytosolic redox-regulating enzyme modulated by Nrf2-mediated stress signaling pathways, with an established role in regulation of stress-related transcription factors. In these studies we investigate the role of NQO1 in regulation of mitogen-activated protein kinase (MAPK) signaling pathways. Quantitative PCR and western blot studies showed that constitutive levels of several MAPK members are upregulated in NQO1-null mouse skin as well as in skin-derived keratinocytes, relative to WT. However, though total protein levels are increased, inducibility of these kinases by known MAPK inducers such as EGF and benzo[a]pyrene (BP) is significantly decreased in NQO1-null cells. NQO1 regulation of MAPK signaling was confirmed by studies showing that NQO1 knockdown by siRNA led to decreased MAPK activation, and overexpression of NQO1 protein led to increased MAPK activation by EGF. Similarly, downregulation of activity via dicoumarol caused loss of ERK phosphorylation, while NQO1 activation via t-BHQ caused increased ERK phosphorylation, which was blocked by MAPK pathway-specific inhibitors. To investigate the functional role of MAPK deactivation in skin-derived keratinocytes, studies with BP and menadione showed that lack of NQO1 expression led to increased susceptibility to ROS generation, and that this ROS generation causes increased toxicity. Taken together, these results show a significant role for NQO1 in regulation of MAPK signaling pathways, which ultimately lead to protection against ROS-mediated apoptosis. Citation Format: Brad A. Patrick, Anil K. Jaiswal. NAD(P)H:quinone oxidoreductase 1 (NQO1) regulates MAPK activation and cellular protection against chemical stress. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4306. doi:10.1158/1538-7445.AM2013-4306
A genome-wide association study identifies CDHR3 as a susceptibility locus for early childhood asthma with severe exacerbations
Authors: Klaus Bønnelykke, Patrick Sleiman, Kasper Nielsen, Eskil Kreiner-Møller, Josep M Mercader, Danielle Belgrave, Herman T den Dekker, Anders Husby, Astrid Sevelsted, Grissel Faura-Tellez, Li Juel Mortensen, Lavinia Paternoster, Richard Flaaten, Anne Mølgaard, David E Smart, Philip F Thomsen, Morten A Rasmussen, Silvia Bonàs-Guarch, Claus Holst, Ellen A Nohr, Rachita Yadav, Michael E March, Thomas Blicher, Peter M Lackie, Vincent W V Jaddoe, Angela Simpson, John W Holloway, Liesbeth Duijts, Adnan Custovic, Donna E Davies, David Torrents, Ramneek Gupta, Mads V Hollegaard, David M Hougaard, Hakon Hakonarson, Hans Bisgaard
Journal: Nature Genetics (2013)
Occult pulmonary haemorrhage in leukaemia.
Authors: D W Golde, W L Drew, H Z Klein, T N Finley, M J Cline
Journal: BMJ (1975)

Through gleeding into the lung parenchyma is responsible for morbidity and mortality in patients with leukaemia pulmonary haemorrhage is seldom diagnosed during life. We diagnosed occult pulmonary haemorrhage in five leukaemic patients with unexplained infiltrates on chest roetgenograms by examining alveolar macrophages retrieved by bronchopulmonary lavage. Macrophage haemosiderin content was greatly increased in the patients with pulmonary haemorrhage as compared to normal and thrombocytopenic control subjects. Haemoglobin and intact erythrocytes in alveolar macrophages were taken as evidence of recent haemorrhage. Intrapulmonary bleeding may occur often in patients with leukaemia, and bronchopulmonary lavage offers a safe approach to diagnosis and allows for concomitant identification of pulmonary infection.
Study of Heart Mitochondria and Glycolytic Metabolism in Experimentally Induced Cardiac Failure
Authors: ARNOLD SCHWARTZ, KWANG SOO LEE
Journal: Circulation Research (1962)

Studies were made on the biochemical activity of mitochondria and of homogenates obtained from normal hearts and from hearts after experimentally induced failure. The principal types of failure investigated were: "chronic" congestive failure and acute failure in the guinea pig. The "chronic" failure was induced in from 2 to 10 days by a partial constriction of the ascending aorta, while the acute type of failure was induced by a more severe aortic constriction of a similar type. Various physiological parameters were studied. The "chronic" animals exhibited tachycardia, elevated right ventricular systolic pressure and a significant depression of myocardial contractility. In addition, a highly significant increase in cardiac tissue mass was observed. Passive congestion of the liver, spleen, kidneys, and lungs was evident. Mitochondria isolated from the hearts of guinea pigs in "chronic" failure exhibited a significant depression of metabolic activity. Thus phosphorylation associated with the oxidation of glutamate, succinate, or α-ketoglutarate was uncoupled in mitochondria isolated from the "failed" heart. Cardiac glycosides administered to animals with experimental cardiac failure did not alter the uncoupled state of the mitochondria, although these agents effected a significant improvement in cardiac contractility. The ATPase activity of the "failed" mitochondria was normal. Experiments concerning the localization of the site or sites of uncoupling of oxidative phosphorylation in the "failed" mitochondria revealed that the defect probably resided in the phosphorylation step associated with the electron transfer between cytochrome C to oxygen. Homogenates prepared from hearts of chronically failing animals were markedly depressed with respect to oxygen and glucose consumption and lactic acid formation. Mitochondria isolated from acutely failed guinea pig hearts exhibited a "mild" uncoupling of oxidative phosphorylation manifested as a decrease in responsiveness to a phosphate acceptor system. This was a graded effect, increasing in severity with increasing duration of aortic constriction. On the basis of the present study, it is possible that uncoupling of oxidative phosphorylation in heart mitochondria may play a role in the development of congestive cardiac failure.
Angiotensin AT1 receptor blockade abolishes the reflex sympatho-excitatory response to adenosine.
Authors: G A Rongen, S C Brooks, S i Ando, B L Abramson, J S Floras
Journal: Journal of Clinical Investigation (1998)

We tested the hypothesis that endogenous angiotensin II participates in the direct and reflex effects of adenosine on the sympathetic nervous system. Nine healthy men were studied after 1 wk of the angiotensin II type I receptor antagonist losartan (100 mg daily) or placebo, according to a double-blind randomized crossover design. Bilateral forearm blood flows, NE appearance rates, and total body NE spillover were determined before and during graded brachial arterial infusion of adenosine (0.5, 1.5, 5, and 15 microg/100 ml forearm tissue) and nitroprusside. Adenosine increased total body NE spillover (P < 0.05) whereas nitroprusside did not. Losartan lowered BP (P < 0.05), had no effect on total body NE spillover at rest, or forearm vasodilation during either infusion, but reduced the systemic noradrenergic response to adenosine from 1.0+/-0.4 nmol/min on the placebo day to 0.2+/-0.3 nmol/min (P < 0.01), and forearm NE appearance rate in response to adenosine was lower in the infused, as compared with the contralateral arm (P = 0.04). The sympatho-excitatory reflex elicited by adenosine is mediated through pathways involving the angiotensin II type I receptor. Interactions between adenosine and angiotensin II may assume importance during ischemia or congestive heart failure and could contribute to the benefit of converting enzyme inhibition in these conditions.
Renin and Myocardial Infarction in Hypertension
Authors: Victor J. Dzau
Journal: New England Journal of Medicine (1991)

HYPERTENSION is a major risk factor for cardiovascular disease. In its pathophysiologic features and clinical sequelae, hypertension is recognized to be a heterogeneous disorder. Although some patients are at increased risk for coronary heart disease, others seem not to be. In the past several years, much effort has been made to identify the factors that increase the risk of coronary heart disease in subjects with hypertension and to understand the pathophysiologic features of the ischemic events in such cases. Accordingly, epidemiologic studies have documented the importance of factors such as hypercholesterolemia, glucose intolerance, cardiac hypertrophy, and cigarette smoking to the . . .
Maximal Oxygen Uptake
Authors: Jere H. Mitchell, Gunnar Blomqvist
Journal: New England Journal of Medicine (1971)

KNOWLEDGE of how oxygen is transported from the ambient air to the tissue cells of the body is essential to an understanding of the mechanisms by which the body adapts to the oxygen demands of muscular exercise. The requirement of oxygen by the various tissue cells of the body is met by the combined cardiovascular and pulmonary systems, which function as a unit termed the oxygen transport system of the body.If a person is subjected to progressively increasing work loads, there is a linear relation between work load and oxygen uptake until the maximal oxygen uptake is reached. Heavier . . .
Measuring Vibration Sensations With Graduated Tuning Fork: Simple and Reliable Means to Detect Diabetic Patients at Risk of Neuropathic Foot Ulceration
Authors: Charles Thivolet, James El Farkh, Antoinette Petiot, Chantal Simonet, Jacques Tourniaire
Journal: Diabetes Care (1990)

To find a simple and reliable means to measure vibration sensations, 189diabetic patients and 88 control subjects were tested at different sites with a graduated tuning fork. Within-test variation at big toes reached 8.4% in diabetic patients vs. 2.2% in control subjects. Mean contralateral variation was 7.5% in diabetic patients vs. 2.5% in control subjects. Tuning-fork sensations were inversely correlated with duration of diabetes, whereas no correlation was found with HBA1c levels or the severity of retinopathy. Ninety-nine (52%) patients had vibratory sensation at big toes of &amp;lt;99th percentile of normal values for age. In addition, 51% of the patients with clinical symptoms at extremities (n = 67), 70% of the patients without tendon reflexes (n = 50), and 75% of the patients with abnormal nerve conduction velocities (n = 60) also had low vibration sensations. All patients with lower-limb injuries (n = 7) had values at big toes of &amp;lt;2. Altogether, the graduated tuning fork represents a simple and reliable alternative to quantitate vibration sensations. Long-term follow-up of asymptomatic patients willindicate whether these abnormalities reflect underlying neuropathy. Patientswith abnormal values at screening will necessitate additional investigationsand special foot-care education programs.