tbuckley/cabot-search huggingface dataset:
Phase III Double-Blind Study of Glutamine Versus Placebo for the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy
Authors: Timothy F. Kozelsky, Gregory E. Meyers, Jeff A. Sloan, Thomas G. Shanahan, Stephen J. Dick, Randy L. Moore, George P. Engeler, Albert R. Frank, Timothy K. McKone, Rodolfo E. Urias, Miljenko V. Pilepich, Paul J. Novotny, James A. Martenson
Journal: Journal of Clinical Oncology (2003)

A phase III, randomized, double-blind study was conducted by the North Central Cancer Treatment Group to determine the efficacy and toxicity of oral glutamine for the prevention of acute diarrhea in patients receiving pelvic radiation therapy (RT).All 129 patients enrolled from 14 institutions between February 1998 and October 1999 were eligible. Patients received 4 g of glutamine or placebo orally, twice a day, beginning with the first or second day of RT and continuing for 2 weeks after RT. During treatment, patients were assessed weekly for toxicity, and a bowel function questionnaire was administered. The primary measures of treatment efficacy were diarrhea levels measured by maximum grade of diarrhea, incidence of diarrhea, and average diarrhea score. After completion of RT, the bowel function questionnaire was administered weekly for 4 weeks and at 12 and 24 months. Toxicity was measured by National Cancer Institute common toxicity criteria.The median age of patients was 69 years (range, 34 to 86 years). The two treatment arms were balanced with respect to all baseline factors. There were no significant differences in toxicity by treatment. Quality-of-life scores and the mean number of problems reported on the bowel function questionnaire were virtually identical for both treatment groups. The incidence of grade 3 or higher diarrhea was 20% for the glutamine arm and 19% for the placebo arm (P =.99). The maximum number of stools per day was 5.1 for the glutamine arm and 5.2 for the placebo arm (P =.99).There is no evidence of a beneficial effect of glutamine during pelvic RT.
Systemic Carnitine Deficiency
Authors: J. D. McGarry, D. W. Foster
Journal: New England Journal of Medicine (1980)

Carnitine was discovered in 1905, and its structure was established in 1927. It is a relatively simple molecule that is synthesized from lysine, with terminal methyl groups donated by S-adenosylmethionine. From studies in lower species it is thought that the immediate precursor γ-butyrobetaine can be formed in many tissues (e.g., kidney, muscle, and heart), but that hydroxylation to carnitine occurs to an important extent only in liver, as shown below: Carnitine synthesized in the hepatocyte is released into plasma for transfer to peripheral tissues, where it is taken up against a concentration gradient by means of a transport system that . . .
Targeted expression of uncoupling protein 2 to mouse liver increases the susceptibility to lipopolysaccharide/galactosamine-induced acute liver injury
Authors: Yingli Shang, Yong Liu, Lei Du, Youliang Wang, Xuan Cheng, Weiming Xiao, Xiaohui Wang, Haijing Jin, Xiao Yang, Shusen Liu, Quan Chen
Journal: Hepatology (2009)

Normal hepatocytes do not express endogenous uncoupling protein 2 (UCP2) in adult liver, although Kupffer cells do, and it is strikingly induced in hepatocytes in steatotic liver and obese conditions. However, the direct link of UCP2 with the pathogenic development of liver diseases and liver injury remains elusive. Here we report that targeted expression of UCP2 to mouse liver increases susceptibility to acute liver injury induced by lipopolysaccharide (LPS) and galactosamine (GalN). UCP2 appears to enhance proton leak, leading to mild uncoupling in a guanosine diphosphate-repressible manner. Indeed, mitochondria from the genetically manipulated mouse liver have increased state 4 respiration, lower respiratory control ratio, and reduced adenosine triphosphate (ATP) levels, which altered mitochondrial physiology. To address the underlying mechanism of how UCP2 and the reduced energy coupling efficiency enhance cell death in mouse liver, we show that the reduced ATP levels lead to activation of 5'AMP-activated protein kinase (AMPK) and its downstream effector, c-Jun N-terminal kinase; thus, the increased sensitivity toward LPS/GalN-induces apoptosis. Importantly, we show that inhibition of UCP2 activity by its pharmacological inhibitor genipin prevents LPS/GalN-induced ATP reduction, AMPK activation, and apoptosis. Also, inhibition of ATP production by oligomycin promotes LPS/GalN-induced cell death both in vivo and in vitro.Our results clearly show that targeted expression of UCP2 in liver may result in compromised mitochondrial physiology that contributes to enhanced cell death and suggests a potential role of UCP2 in the development of liver diseases.
Leukemia and Radium Groundwater Contamination
Authors: Anthony P. Polednak
Journal: JAMA (1986)

To the Editor.—  In their report on an association between leukemia rates and radium groundwater contamination, Lyman et al 1 cited as support for a possible causal interpretation a report on radium dial painters of which I was the senior author. 2 This requires clarification.  Among 634 female radium dial painters first employed between 1915 and 1929 in the United States, three deaths were coded to leukemia and aleukemia vs 1.41 expected on the basis of US death rates. 2 These numbers are small, and the standardized mortality ratio was not statistically significant.  More recent reports using additional information on larger series of radium dial workers 3,4 have concluded that the incidence of and mortality from leukemia are not significantly increased. The latter reports included data on women employed after 1930 and exposed to lower doses of radium than earlier workers. The statistical power of some of these tests of
Colonic Perforations after Gas Explosion Induced by Argon Plasma Coagulation
Authors: N. Pichon, F. Maisonnette, F. Cessot, M. Sodji, D. Sautereau
Journal: Endoscopy (2004)

Three factors are necessary to trigger an explosion of intestinal gases: the presence of combustible gases (hydrogen, methane), the presence of combustive gas (oxygen), and an initiating heat source (endoscopic or surgical electrocautery) [1].
Cost Containment and Hypertension
Authors: LAWRENCE Z. FEIGENBAUM
Journal: Annals of Internal Medicine (1988)

Letters and Corrections1 January 1988Cost Containment and HypertensionLAWRENCE Z. FEIGENBAUM, M.D.LAWRENCE Z. FEIGENBAUM, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-108-1-148_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Dr. Moser's editorial (1) is an important statement on the management of hypertension. I strongly concur that the newer, expensive drugs are not "indicated as initial therapy." However, I am puzzled that reserpine was not considered, since cost containment was the major focus of his editorial Reserpine as a second-step drug should have been mentioned because it is the least expensive hypertensive agent and is well established as being highly effective when added to a thiazide.To exclude reserpine on the basis of adverse effects does not seem reasonable. Reserpine's commonest adverse effects are nasal congestion and...References1. MOSER M. "Cost containment" in the management of hypertension. Ann Intern Med. 1987;107:107-9. LinkGoogle Scholar2. FEIGENBAUM L. Drug choice for treatment of hypertension at 'step 2'. West J Med. 1979;130:391-3. MedlineGoogle Scholar3. LUXENBERGFEIGENBAUM JL. The use of reserpine for elderly hypertensive patients. J Am Geriatr Soc. 1983;30:556-9. CrossrefGoogle Scholar4. FINNERTYGYFTOPOULOSBERRYMCKENNEY FGCA. Step 2 regimens in hypertension. JAMA. 1979;241:579-81. CrossrefMedlineGoogle Scholar5. . Low dose v standard dose of reserpine: a randomized, double-blind, multiclinic trial in patients taking chlorthalidone. JAMA. 1982;248:2471-7. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: LAWRENCE Z. FEIGENBAUM, M.D.Affiliations: San Francisco Institute on Aging Mount Zion Hospital and Medical Center San Francisco, CA 94120 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byReserpine for HypertensionCorrection: Reserpine DosageLAWRENCE Z. FEIGENBAUM, M.D. 1 January 1988Volume 108, Issue 1Page: 148-149KeywordsDrug therapyDrugsHypertensionReserpine ePublished: 1 December 2008 Issue Published: 1 January 1988 PDF downloadLoading ...
462. Busulfan Dose Escalation to Increase Gene Marking of Hematopoietic Stem Cells by Lentiviral Vectors in Infant Rhesus Monkeys
Authors: Christoph A. Kahl, Alice F. Tarantal, Chang I. Lee, Daniel F. Jimenez, Christopher Choi, Karen Pepper, Denise Peterson, Misty D. Fletcher, Alyssa C. Leapley, Donald B. Kohn
Journal: Molecular Therapy (2005)
Bone Marrow Transplantation for Patients with Chronic Myeloid Leukemia
Authors: John M. Goldman, Jane F. Apperley, Lydia Jones, Robert Marcus, Alan W.G. Goolden, Richard Batchelor, Geoffrey Hale, Herman Waldmann, Cecil D. Reid, Jill Hows, Edward Gordon-Smith, Daniel Catovsky, David A.G. Galton
Journal: New England Journal of Medicine (1986)

Between February 1981 and December 1984 we treated 52 patients with chronic myeloid leukemia in the chronic phase and 18 patients with more advanced disease by high-dose chemoradiotherapy followed by allogeneic bone marrow transplantation using marrow cells from HLA-identical sibling donors. In addition, the 40 patients who had not previously undergone splenectomy received radiotherapy to the spleen. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with donor marrow depleted of T cells. Of the 52 patients treated in the chronic phase, 38 are alive after a median follow-up of 25 months (range, 7 to 50); the actuarial survival at two years was 72 percent, and the actuarial risk of relapse was 7 percent. Of the 18 patients with more advanced disease, 4 have survived; the actuarial two-year survival was 18 percent, and the actuarial risk of relapse was 42 percent. We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase of chronic myeloid leukemia. T-cell depletion may have reduced the incidence and severity of graft versus host disease. The value of irradiation to the spleen before transplantation has not been established. (N Engl J Med 1986; 314:202–7.)
Corrigendum to “Ultrasound-based molecular imaging and specific gene delivery to mesenteric vasculature by endothelial adhesion molecule targeted microbubbles in a mouse model of Crohn's disease” [J. Control. Release 165 (2013) 216–225]
Authors: José L. Tlaxca, Joshua J. Rychak, Peter B. Ernst, Prasad R. Konkalmatt, Talent I. Shevchenko, Theresa T. Pizarro, Jesús Rivera-Nieves, Alexander L. Klibanov, Michael B. Lawrence
Journal: Journal of Controlled Release (2013)
Effect of Hyperoxic Hypercapnia on Variational Activity of Breathing
Authors: AMAL JUBRAN, BRYDON J. B. GRANT, MARTIN J. TOBIN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Dysrhythmias of breathing occur in several clinical disorders, but their mechanistic basis is obscure. To understand their pathophysiology, factors responsible for the variability of breathing need to be defined. We studied the effect of hyperoxic hypercapnia (CO2) on the variational activity of breathing in 14 volunteers before and after delivering CO2 nonobstrusively via a plastic hood. Compared with air, CO2 increased the gross variability of minute ventilation (V˙ i) and tidal volume (Vt), and decreased that of inspiratory time (Ti) and expiratory time (Te) (all p < 0.03). CO2 increased the autocorrelation coefficient at a lag of one breath for V˙ i (p < 0.05), the number of consecutive breath lags having significant autocorrelation coefficients for V˙ i and Vt (both p < 0.01), and the cycle time of oscillations in V˙ i (p = 0.03) and Vt (p = 0.04). Uncorrelated random behavior constituted ⩾ 80% of the variance of each breath component, correlated behavior represented 9 to 20%, and oscillatory behavior represented < 1% during both air and CO2. CO2 increased the correlated behavior of volume components, which was accompanied by development of low-frequency oscillations with a cycle time consistent with central chemoreceptor activation.
Prognostic Value of Bone Scintigraphy in Cancer Patients With Osteonecrosis of the Jaw
Authors: Samer George Hakim
Journal: Clinical Nuclear Medicine (2012)

To the Editor With great interest, I read the article by Van den Wyngaert et al1 published in Clinical Nuclear Medicine (2011;36:17–20). Better late than never. The authors reported on the potential detection of bisphosphonate osteonecrosis of the jaw (BP ONJ) using bone scintigraphy. They performed planar bone scintigraphy and SPECT in 22 patients with stage 1 to 3 BP ONJ and postulated that SPECT will detect BP ONJ lesions and provide prognostic information. Apart from the very limited number of patients and sample power, there is something missing in the interpretation of results, which, in my opinion, ought to be resolved. Bone scintigraphy as such, including SPECT acquisition, represents a surrogate parameter reflecting osteoblasts’ activity by tracer uptake in ROI. This is, in turn, the hallmark of osteomyelitic changes or a sign of reparative process after trauma, surgery, and bone remodeling.2–4 Although the pathogenesis of BP ONJ is not yet completely understood, it is assumed that this condition is related to alteration of bone remodeling because of the inhibition of osteoclast function and bone turnover.5 Taking these aspects into consideration, the findings presented in this study are “nonspecific” in the sense of not being related to osteonecrosis, which is “invisible” by bone scintigraphy, but to the more or less associated osteomyelitic lesion or reparative process. This is, at the same time, the simple explanation of the inhomogeneous distribution of scintigraphic findings among the 3 groups, namely the lesions induced various types of inflammatory and reparative changes in the affected bone. I found the article by Van den Wyngaert et al very interesting; apparently, the reviewer did so too. However, I missed this critical aspect in the discussion and had to make up for the readers of Clinical Nuclear Medicine. Samer George Hakim, MD, DMD, PhD Department of Oral and Maxillofacial Surgery University of Luebeck Luebeck, Germany [email protected]
Falling EU population will affect healthcare provision
Authors: Rory Watson
Journal: BMJ (2005)

The European Union is facing unprecedented demographic change, according to the European Commission, which is so concerned at the implications of a falling population that it has issued a consultation paper on the subject.

The native population of the EU's 25 member countries grew by only 0.04% in 2003, and of the 10 countries that joined the EU last year, all except Cyprus and Malta saw their populations …
The role of tau in neurodegeneration
Authors: Tania F Gendron, Leonard Petrucelli
Journal: Molecular Neurodegeneration (2009)

Since the identification of tau as the main component of neurofibrillary tangles in Alzheimer's disease and related tauopathies, and the discovery that mutations in the tau gene cause frontotemporal dementia, much effort has been directed towards determining how the aggregation of tau into fibrillar inclusions causes neuronal death. As evidence emerges that tau-mediated neuronal death can occur even in the absence of tangle formation, a growing number of studies are focusing on understanding how abnormalities in tau (e.g. aberrant phosphorylation, glycosylation or truncation) confer toxicity. Though data obtained from experimental models of tauopathies strongly support the involvement of pathologically modified tau and tau aggregates in neurodegeneration, the exact neurotoxic species remain unclear, as do the mechanism(s) by which they cause neuronal death. Nonetheless, it is believed that tau-mediated neurodegeneration is likely to result from a combination of toxic gains of function as well as from the loss of normal tau function. To truly appreciate the detrimental consequences of aberrant tau function, a better understanding of all functions carried out by tau, including but not limited to the role of tau in microtubule assembly and stabilization, is required. This review will summarize what is currently known regarding the involvement of tau in the initiation and development of neurodegeneration in tauopathies, and will also highlight some of the remaining questions in need of further investigation.
Combined Abnormalities of Semilunar Valves
Authors: Keiji Hirooka, Shuji Hashimoto, Norio Tanaka, Naoaki Yamada, Yoshikazu Masuda, Akihisa Hanatani, Satoshi Nakatani, Yoshio Yasumura, Kunio Miyatake, Masakazu Yamagishi
Journal: Circulation (2001)
Waveform and spectral analysis of crackles.
Authors: M Mori, K Kinoshita, H Morinari, T Shiraishi, S Koike, S Murao
Journal: Thorax (1980)

Crackles were recorded from six patients, four with tuberculosis and two with chronic bronchitis. It was observed by waveform and spectral analysis that most of the frequency components of a crackle were limited within a range of 0.1 to 1 kHz. Characteristically, waveforms of crackles were separable into two segments, initial "starting segments" and subsequent "decay segments." It is suggested that the former represents a shock wave caused by an abrupt opening of the airway and that the latter is a damped sinusoid caused by this shock wave exciting a resonator in the lung. It is speculated that the starting segment is determined by the pressure ratio at the site of the airway opening, and the decay segment by the resonant frequency and the quality factor of the resonator. Because transmission of a crackle is highly directional the waveforms recorded on the chest wall are modified by the positional relationship between the sound source and the microphone.
Clinical Implications of the DREAM Study
Authors: Mayer B. Davidson
Journal: Diabetes Care (2007)

ecause impaired fasting glucose (IFG) in the DREAM study (1) was defined at the time of recruitment as a fasting plasma glucose (FPG) concentration of Ն6.1 to Ͻ7.0 mmol/l (110 -125 mg/dl), Dr. Kanat (2) raises the possibility that patients with FPG levels of 5.6 -6.0 mmol/l (100 -109 mg/dl), which fall within the more recent American Diabetes Association definition of IFG (3), might not respond similarly to rosiglitazone.This seems unlikely, since these subjects have less of an abnormality of glucose homeostasis than those who fulfill the older criterion.Furthermore, there are two bits of evidence against his contention.In the Diabetes Prevention Program (DPP) (4), subjects were selected with FPG concentrations as low as 5.3 mmol/l (95 mg/dl) and responded to the drug and lifestyle interventions.Second, in the same study (5), before the troglita-
Company denies that its coding advice is aimed at improving mortality data
Authors: N. Hawkes
Journal: BMJ (2013)

The health analytics company CHKS has denied that it sought to help hospitals improve their mortality figures by advising changes in coding practices.

The charge was implied in evidence given to the public inquiry into Mid Staffordshire NHS Foundation Trust by Brian Jarman, director of the Dr Foster Unit at Imperial College London, who presented as part of his evidence a press release from CHKS dated 11 December 2008.

In it CHKS recorded that advice it had given to Medway NHS Foundation Trust about coding hospital care at the end of life …
The Management of Congenital Deformities of the Sternum
Authors: Lester IT. Martin
Journal: JAMA (1962)

ALL DEGREES of developmental variation in the shape of the thoracic cage are known to occur, varying from those which are slight and inconsequential to those which are quite serious. The more severe forms may be crippling or in some instances even fatal. The surgeon, as well as the pediatrician or family doctor, must frequently decide whether surgical correction of the deformity is necessary or advisable. The purpose of this paper is to present our experience at the Cincinnati Children's Hospital in the management of congenital deformities of the chest wall. Etiology Several different theories have been proposed to explain the etiology of sternal deformities, but the most recent evidence indicates that an arrest or alteration of embryologie development is probably responsible in many cases. There can be little dispute that the bifid sternum represents an arrest of development since embryologically the sternum develops from 2 lateral cartilagenous bars which
Biological drivers of zooplankton patchiness
Authors: Carol L. Folt, Carolyn W. Burns
Journal: Trends in Ecology & Evolution (1999)

Until recently, biological drivers of plankton aggregation were under-appreciated, because most studies concentrated on physical processes. New technological advances, novel experiments and theory have shifted focus to the pivotal role of behaviour in plankton patch dynamics. Our review highlights four biological drivers of zooplankton spatial patchiness and brings together recent research on well studied marine and freshwater taxa, primarily copepods and cladocerans. Diverse and powerful behavioural responses by zooplankton to physical and chemical signals are shown to contribute to the formation and breakdown of zooplankton patches over several different spatial scales.
The effect of propranolol on microvascular injury in acute myocardial ischemia.
Authors: R A Kloner, M C Fishbein, R S Cotran, E Braunwald, P R Maroko
Journal: Circulation (1977)

The purpose of this study was to determine whether propranolol, which has been shown to reduce the extent of myocardial infarction, reduces microvascular injury which may play a role in exacerbating ischemia. Saline (10 dogs) or propranolol (2 mg/kg i.v., 7 dogs) was injected prior to a one hour occlusion of the left anterior descending coronary artery. Carbon black (1 ml/kg), which labels damaged and leaky vessels, was injected 5 min after release of the occlusion and allowed to circulate for two hours. By morphometric analysis of 1 micron thick sections, 75 +/- 12% of vessels and 84 +/- 7% of myocardial cells showed damage in untreated dogs; only 2 +/- 1% of vessels and 9 +/- 8% of myocardial cells showed damage in the propranolol-treated dogs (P less than 0.001). The number of carbon black-labeled vessels/10 fields/biopsy from comparable areas of ischemic tissue was 55 +/- 7 in untreated dogs and 27 +/- 3 in propranolol-treated dogs (P less than 0.001). The results suggest that propranolol not only protects the ischemic myocardial cell, but also significantly decreases the ischemic microvascular changes.