tbuckley/cabot-search huggingface dataset:
Administration of atrial natriuretic factor inhibits sodium-coupled transport in proximal tubules.
Authors: T G Hammond, A N Yusufi, F G Knox, T P Dousa
Journal: Journal of Clinical Investigation (1985)

The newly discovered peptides extracted from cardiac atria, atrial natriuretic factors (ANFs), when administered parenterally cause renal hemodynamic changes and natriuresis. The nephron sites and cellular mechanism accounting for profound increase in Na+ excretion in response to ANFs are not yet clarified. In the present study we investigated whether synthetic ANF peptide alters the reabsorption of Na+ and reabsorption of solutes cotransported with Na+ in the proximal tubules of rats. Synthetic ANF peptide consisting of 26 amino acids, 4 micrograms/kg body wt/h, or vehicle in controls, was infused to surgically thyroparathyroidectomized anesthetized rats. After determination of the fractional excretion (FE) of electrolytes (Na+, K+, Pi, Ca2+, Mg2+, HCO3), the kidneys were removed and luminal brush border membrane vesicles (BBMVs) were prepared from renal cortex. Solute transport was measured in BBMVs by rapid filtration techniques. Infusion of ANF peptide increased FENa, FEPi, and FEHCO3; but FECa, FEK, and FEMg were not changed. The increase in FENa was significantly correlated, on the one hand, with increase of FEPi (r = 0.9, n = 7; P less than 0.01) and with increase of FEHCO3 (r = 0.89, n = 7; P less than 0.01). On the other hand, FENa did not correlate with FEK, FECa, or with FEMg. The Na+ gradient-dependent uptake of Pi by BBMVs prepared from renal cortex of rats receiving ANF infusion was significantly (P less than 0.05) decreased (-25%), whereas the Na+ gradient-dependent uptake of L-[3H]proline and of D-[3H]glucose or the diffusional uptake of 22Na+ were not changed. ANF-elicited change in FEPi showed a close inverse correlation with decrease of Na+-dependent Pi uptake by BBMVs isolated from infused rats (r = 0.99, n = 7; P less than 0.001). Direct addition of ANF to BBMVs in vitro did not change the Na+ gradient-dependent Pi uptake. In rats infused with ANF, the rate of amiloride-sensitive Na+-H+ exchange across the brush border membrane (BBM) was significantly (P less than 0.05) decreased (-40%), whereas the diffusional 22Na+ uptake (0.5 min) and the equilibrium (120 min) uptake of 22Na+ were not changed. The inhibition of Na+-H+ exchange after ANF was likely due to alteration of the BBM antiporter itself, in that the H+ conductance of BBMVs was not increased. We conclude that synthetic ANF (a) decreases tubular Na+ reabsorption linked to reabsorption of HCO3 in proximal tubules, and (b) inhibits proximal tubular reabsorption of Pi coupled to Na+ reabsorption, independent of secretion and/or action of parathyroid hormone or calcitonin. These ANF effects are associated with inhibition of Na+-Pi synport and of Na+-H+ antiport in luminal BBMs. Our findings document that inhibition of Na+-coupled transport processes in proximal tubules is an integral part of the renal response to ANF.
Functional Analysis of Human <i>MLH1</i> Variants Using Yeast and <i>In vitro</i> Mismatch Repair Assays
Authors: Masanobu Takahashi, Hideki Shimodaira, Corinne Andreutti-Zaugg, Richard Iggo, Richard D. Kolodner, Chikashi Ishioka
Journal: Cancer Research (2007)

The functional characterization of nonsynonymous single nucleotide polymorphisms in human mismatch repair (MMR) genes has been critical to evaluate their pathogenicity for hereditary nonpolyposis colorectal cancer. We previously established an assay for detecting loss-of-function mutations in the MLH1 gene using a dominant mutator effect of human MLH1 expressed in Saccharomyces cerevisiae. The purpose of this study is to extend the functional analyses of nonsynonymous single nucleotide polymorphisms in the MLH1 gene both in quality and in quantity, and integrate the results to evaluate the variants for pathogenic significance. The 101 MLH1 variants, which covered most of the reported MLH1 nonsynonymous single nucleotide polymorphisms and consisted of one 3-bp deletion, 1 nonsense and 99 missense variants, were examined for the dominant mutator effect by three yeast assays and for the ability of the variant to repair a heteroduplex DNA with mismatch bases by in vitro MMR assay. There was diversity in the dominant mutator effects and the in vitro MMR activities among the variants. The majority of functionally inactive variants were located around the putative ATP-binding pocket of the NH(2)-terminal domain or the whole region of the COOH-terminal domain. Integrated functional evaluations contribute to a better prediction of the cancer risk in individuals or families carrying MLH1 variants and provide insights into the function-structure relationships in MLH1.
P44 How Long is short term Oxygen Therapy? Home Oxygen Prescriptions Post Hospitalisation
Authors: JL Gallagher, G McKernan, L Slater, A DeRamon
Journal: Thorax (2012)

<h3>Introduction</h3> Long-term oxygen therapy (LTOT) has been shown to improve survival in some patients with chronic obstructive pulmonary disease (COPD); generalisation to other groups of hypoxic patients is less clear. The British Thoracic Society recommend LTOT should be prescribed to hypoxic patients after appropriate assessment during a period of clinical stability.¹ In practise LTOT is frequently prescribed following hospitalisation. This form of oxygen therapy has been termed short-term oxygen therapy (STOT). We sought to audit our practise of prescribing home oxygen therapy to hypoxic patients following hospital admission with an exacerbation of a respiratory disorder. <h3>Method</h3> We performed a retrospective case note audit of 30 patients [13 male] commenced on home oxygen therapy at discharge over a 6 month period recording patient demographics, smoking status, underlying diagnosis, compliance with BTS oxygen prescribing guidelines and the outcome of follow-up. <h3>Results</h3> The mean age was 71 years (48–91yrs); 17% current smokers, 73% ex-smokers. COPD was the most common diagnosis in 80% (24/30); the mean FEV1 1.1L (52% predicted). No definitive diagnosis was documented in 10% (3/30) with 10% diagnosed with sarcoidosis, idiopathic pulmonary fibrosis or lung cancer. 64% (19/30) of patients met BTS LTOT criteria, (80% (19/24) with COPD), 33% (10/30) did not and 3% (1/30) were prescribed palliative oxygen. 93% of patients (27/29) were followed up at 3 months. The mean oxygen flow rate required was 1.4L/min; oxygen flow rate was altered in 63%. The overwhelming majority of our patients, 90% (26/29), continued with LTOT after reassessment at 3 months and 79% (23/29) at 6 months. <h3>Conclusion</h3> Our audit shows that the majority of patients commenced on oxygen therapy post hospitalisation met the criteria for LTOT and continued to require oxygen at 3 and 6 months; this is a higher figure than quoted in the majority of the literature. This suggests our patients are presenting late with underlying chronic lung disease; we need to strive to identify these patients earlier. There is still a lack of evidence-based guidelines for STOT and further research in this area is needed. <h3>References</h3> BTS Home Oxygen Service in England and Wales. January 2006.
CTCF Regulates Ataxin-7 Expression through Promotion of a Convergently Transcribed, Antisense Noncoding RNA
Authors: Bryce L. Sopher, Paula D. Ladd, Victor V. Pineda, Randell T. Libby, Susan M. Sunkin, James B. Hurley, Cortlandt P. Thienes, Terry Gaasterland, Galina N. Filippova, Albert R. La Spada
Journal: Neuron (2011)
Sports Injuries: Mechanisms, Prevention, and Treatment
Authors: Christine E. Haycock
Journal: JAMA (1985)

This fascinating compendium of the mechanisms of sports injuries and methods for their prevention deals essentially with the emergency treatment of the acute injury on the field. It is not intended as a reference to treatment in depth, but the latter chapters do go into considerable detail in specific specialty areas. The chapters are mainly based on each major sport. Because several sports that are not popular in the United States, such as rugby, are presented by overseas authors, they provide the reader with better insight. I would have liked to have seen cricket covered as well, since, despite its rarity in the United States, it is frequently played in Canada. A historical perspective introduces each sport, and excellent graphic pictures (especially in the chapter on football) illustrate the mechanism of the injury and the pathological damage. Ways the injury might have been prevented by better coaching, officiating (enforcement of
Comparative Trial of Serotonin Antagonists in the Management of Migraine
Authors: J. W. Lance, M. Anthony, B. Somerville
Journal: BMJ (1970)

The effectiveness of five different serotonin antagonists in the prevention of migraine was compared in 290 patients followed for periods of up to three years. Methysergide 3-6 mg. daily was most effective, with 20% of treated patients becoming headache-free and a further 44% remaining more than "half improved." The corresponding figures for BC105 were 10% and 40%, respectively. The results with BC105 were significantly better than those with placebo (P&lt;0·02). The total improvement rates with methdilazine (45%) and cyproheptadine (43%) were better than those with placebo (32%) but did not achieve statistical significance. A new preparation, methylergol carbamide maleate, which is chemically related to methysergide, did not give better results than placebo.
Factors affecting the healing rate of duodenal and pyloric ulcers with low-dose antacid treatment.
Authors: S Massarrat, A Eisenmann
Journal: Gut (1981)

In 80 patients with duodenal ulcer, the effects of various factors--symptoms, endoscopic findings, and peak acid output (PAO)--on the healing rate were studied during eight weeks of outpatient therapy with low-dose antacid (neutralising capacity less than 50 mmol HCl/d). Fifty-six per cent of the ulcers healed. The following unfavourable factors were found to cause a significant delay in ulcer healing: a long duration of pain in the last ulcer relapse and the present period of ulcer pain, smoking, stenosis of the duodenal bulb, and a high PAO. Multiple regression analysis showed that three factors (duration of the present ulcer pain, smoking, and stenosis of the duodenum) had a significant influence on healing rate. According to the results obtained with this method, the patients with no or only one unfavourable factor (n = 35) had the best healing rate: 80%, compared with patients who had two (n = 31) or three (n = 14) unfavourable factors. The healing rate of the latter two groups was 41% and 28%, respectively (p less than 0.001). A prognostic score based on these three factors represents the severity of duodenal-ulcer disease with regard to the healing process under placebo-like doses of antacid.
PROFESSOR KOCHER ON MODERN PROJECTILES IN WARFARE.
Authors: CHARLES G. CANNADAY
Journal: JAMA (1894)

"In the time of peace," it has been said, "prepare for war." This necessary evil must sooner or later come to all countries, judging from the past; its evil consequences are sufficient when happy homes are robbed of fathers, husbands and sons, but when the projectiles are of such a nature as to produce great destruction of tissue, owing to shape and velocity, it becomes all true philanthropists to assist the Red Cross, which will figure so conspicuously in future Italian wars, to bring about such a change in projectiles as will cause the least destruction of tissue compatible with "disabling the enemy and causing him to retire from the field." During the riot in this city in 1893, I had the opportunity of seeing the great amount of mutilation and serious wounds produced by the modern firearms in the hands of our military company—those not instantly killed are so
Rationing in general practice: Commentary: Commendable but confused
Authors: P. Toon
Journal: BMJ (1996)

<h3>Background</h3> In hospital settings (HS), pharmacists´ interventions (PI) can contribute to rational use of antimicrobials. Due to scarce resources, the pharmacist’s time has to be dedicated to interventions with impact on patient outcomes and costs. <h3>Purpose</h3> A systematic review was conducted to summarise published evidence regarding clinical and/or economic outcomes of PI related to antimicrobials in HS to estimate the impact of PI and to identify strategies with higher impact. <h3>Material and methods</h3> A PubMed search of papers published from 2003 to March 2016 was conducted using the terms (’pharmacist*’ OR ‘clinical pharmacist*’) AND (’antimicrobial*’ OR ‘antibiotic*’ OR ‘anti infective*’). Additional references were identified from citations. Inclusion criteria were: comparative studies that assessed clinical or economic impact of PI regarding antimicrobials in HS or those that evaluated intermediate outcomes, microbiological impact or appropriate antimicrobial prescription (AAP). Exclusion criteria were: studies in paediatric, primary care or community settings, and evaluations of multidisciplinary teams. We collected: study design, type of PI, impact of PI and acceptance by physicians. Risk of bias of studies was analysed using Cochrane´s tool.<sup>1</sup> <h3>Results</h3> 23 studies were included; all had a high risk of bias. Most frequent design was before and after without a control group (57%) and 83% were single centre studies. Identified PI were grouped into three types: specific recommendations (SR) (in 22 studies), policy (in 4) and education (in 3). Six studies combined various strategies. A significant positive impact of PI was found in 14 of 17 (82%) studies that evaluated costs, in 11 of 15 (73%) that studied AAP, in 9 of 18 (50%) that analysed clinical outcomes (CO), in 1 of 2 (50%) that assessed microbiological outcomes (MO) and in 3 of 7 (43%) that evaluated adverse drug events (ADE). A combination of SR, education and policy had the highest impact on AAP, CO and costs; SR and education on MO; and dose adjustment on ADE. 70–92% of recommendations were accepted. <h3>Conclusion</h3> Pharmacists´ interventions regarding antimicrobials had a positive impact on appropriate prescribing and patient outcomes, and decreased costs. Combinations of strategies seems to be superior to single strategies. Quality of published studies is poor and better studies are necessary to confirm these results. <h3>References and/or acknowledgements</h3> 1. Available at http://handbook.cochrane.org/chapter_8/8_5_the_cochrane_collaborations_tool_for_assessing_risk_of_bias.htm No conflict of interest
Estimated changes in human exposure to suspended sulfate attributable to equipping light-duty motor vehicles with oxidation catalysts.
Authors: J F Finklea, J Moran, J H Knelson, D B Turner, L E Niemeyer
Journal: Environmental Health Perspectives (1975)

The potential environmental impact of equipping vehicles with oxidation catalysts is estimated. Three independent techniques are used to appraise community exposures. Incremental increases in suspended sulfates and sulfuric acid aerosols are evaluated in terms of the number of vehicles equipped with oxidation catalysts.
Tumor Volume as a Potential Imaging-Based Risk-Stratification Factor in Trimodality Therapy for Locally Advanced Non-small Cell Lung Cancer
Authors: Margaret M. Kozak, James D. Murphy, Meike L. Schipper, Jessica S. Donington, Lisa Zhou, Richard I. Whyte, Joseph B. Shrager, Chuong D. Hoang, Jose Bazan, Peter G. Maxim, Edward E. Graves, Maximilian Diehn, Wendy Y. Hara, Andrew Quon, Quynh-Thu Le, Heather A. Wakelee, Billy W. Loo
Journal: Journal of Thoracic Oncology (2011)
Normal muscle strength and fatigability in patients with effort syndromes: Authors' reply
Authors: M. J Stokes, R. G Cooper, R. H T Edwards
Journal: BMJ (1988)

term approach would be to improve the motorway network linking the towns and cities of Britain.For example, such anomalies as the lack of a motorway link between Scotland and England on either the east or west coasts leads to motorists driving at inappropriately high speeds on dual carriageways.If the number of road traffic accidents is to be reduced realistic solutions must be put forward, allowing drivers to travel at speed between cities but ensuring safe lower speeds within communi- ties where pedestrians and cyclists are so much at risk.
Doctors, one to nine
Authors: C. Douglas
Journal: BMJ (1995)

I do not claim to know much about general practice, but there occurred to me the other day in asupermarket a simple idea which could, quickly and cheaply, transform the efficiency of primary care by addressing the central issue of informed consumer choice.

The present system is wasteful because patients who have a general idea what is wrong with themand what they might need are compelled to spend time waiting for and eventually seeing a doctor whose approach and style might be quite inappropriate to what is required on that particular occasion.

A couple of examples will suffice. A lonely widow with vague headaches coinciding with the anniversary of her bereavement should not encounter anyone who is in the habit of reaching for the …
Our Duties in Reference to the Signing of Lunacy-Certificates
Authors: G. H. Savage
Journal: BMJ (1885)

iris, as after perforated corneal ulcer, or in the' later stages of some glaucomas, or by the lens, as in some cases of dislocation of this body, the proof is convincing.The application of the cautery to the sclero- corneal junction is said to block the outflow, thus proving the same thing.Contraction of the pupil, as after eserine or sleep, increases it probably by the necessarily associated extension and opening out of the fibres of the ligamenturn pectinatuai.It is also indisputable that
Correction of metabolic, craniofacial, and neurologic abnormalities in MPS I mice treated at birth with adeno-associated virus vector transducing the human α-l-iduronidase gene
Authors: Seth D Hartung, Joel L Frandsen, Dao Pan, Brenda L Koniar, Patrick Graupman, Roland Gunther, Walter C Low, Chester B Whitley, R.Scott McIvor
Journal: Molecular Therapy (2004)

Murine models of lysosomal storage diseases provide an opportunity to evaluate the potential for gene therapy to prevent systemic manifestations of the disease. To determine the potential for treatment of mucopolysaccharidosis type I using a gene delivery approach, a recombinant adeno-associated virus (AAV) vector, vTRCA1, transducing the human iduronidase (IDUA) gene was constructed and 1 × 1010 particles were injected intravenously into 1-day-old Idua−/− mice. High levels of IDUA activity were present in the plasma of vTRCA1-treated animals that persisted for the 5-month duration of the study, with heart and lung of this group demonstrating the highest tissue levels of gene transfer and enzyme activity overall. vTRCA1-treated Idua−/− animals with measurable plasma IDUA activity exhibited histopathological evidence of reduced lysosomal storage in a number of tissues and were normalized with respect to urinary GAG excretion, craniofacial bony parameters, and body weight. In an open field test, vTRCA1-treated Idua−/− animals exhibited a significant reduction in total squares covered and a trend toward normalization in rearing events and grooming time compared to control-treated Idua−/− animals. We conclude that AAV-mediated transduction of the IDUA gene in newborn Idua−/− mice was sufficient to have a major curative impact on several of the most important parameters of the disease.
Low-Dose Aspirin for Preeclampsia — The Unresolved Question
Authors: William Barth
Journal: New England Journal of Medicine (1998)

Preeclampsia, defined as hypertension and proteinuria or nondependent edema after 20 weeks' gestation, is a common complication of pregnancy. Endothelial-cell dysfunction with vasospasm, pathologic coagulation, and hypersensitivity to pressor substances further characterize the disorder. When severe, preeclampsia can cause renal failure, hepatic dysfunction, cardiac and pulmonary failure, seizures, and death.Despite more than half a century of intensive research, preeclampsia continues to be a major contributor to maternal and perinatal mortality. Where access to prenatal care and hospital resources is limited, morbidity and mortality rates for both mothers and babies are high. It is therefore not hard to understand the . . .
New Biopsy Forceps for Gastrointestinal Endoscopy
Authors: M. Paternuosto, M. E. Bottiglieri, G. Migliore, C. Civiletti, R. Cuomo
Journal: Endoscopy (2002)

During endoscopy, multiple biopsies are often necessary to clarify certain diagnostic issues, such as gastric Helicobacter pylori infection, the presence and extent of inflammatory bowel disease (IBD), or the presence of malignant lesions. In all of these cases, the endoscopist repeatedly has to insert and withdraw traditional biopsy forceps through the endoscope channel in order to obtain all the mucosal specimens required - making the examination excessively long and reducing patient compliance. In addition, frequent passage through the channel quickly wears out the endoscope.
Residency Programs: Sizes, Types, and Effects
Authors: EDWIN F. ROSINSKI
Journal: Annals of Internal Medicine (1978)

Editorials1 November 1978Residency Programs: Sizes, Types, and EffectsEDWIN F. ROSINSKI, ED.D.EDWIN F. ROSINSKI, ED.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-5-718 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe second report by Weil, Schleiter, and Tarlov, pp. 702-715, in this issue, from the National Study of Internal Medicine Manpower (NSIMM) is an important addition to their first report. The first report (1) was largely descriptive and dealt mainly with numbers of programs, numbers of residents, and sources of support dollars. This second report attempts to characterize the residency training environments by developing a typology of training programs and relating the principal types to a number of variables. The number of programs studied—virtually all of the approved residency programs in internal medicine during the years 1976-77—and the number of...Reference1. TARLOVWEILSCHLEITER APM: National study of internal medicine manpower. I. Residency training 1976-1977. Ann Intern Med 88:413-420, 1978 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Professor of Medical Education School of Medicine University of California San Francisco, California PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByFunctions Containing One Phosphorus and Either Another Phosphorus or As, Sb, Bi, Si, Ge, B or a MetalReferences to Volume 4Program Directors in Internal Medicine: A Survey of Residency ProgramsExit Ramps for Career ChoicesDAVID WOODLEY, M.D. 1 November 1978Volume 89, Issue 5_Part_1Page: 718-718KeywordsResidency Issue Published: 1 November 1978 PDF DownloadLoading ...
Hematology: A Pathophysiological Approach
Authors: Edward J. Benz
Journal: JAMA (1985)

<i>Hematology: A Pathophysiological Approach</i>represents the most recent addition to a strong library of "small" general hematology textbooks. Several excellent texts already available attempt, with reasonable success, to summarize the broad field of hematology in 200 to 400 pages. They offer the best means of introducing material that must be mastered during the brief (two to three week) time blocks allotted to the teaching of hematology in most medical school curricula. Babior and Stossel's work is a notable addition to this group, because it provides a particularly coherent application of basic science principles to the understanding of cellular and biochemical mechanisms causing clinical disorders of the hematopoietic organs. Both authors are major leaders in WBC physiology research, as well as experienced teachers. Their experience is reflected in the emphasis given different topics in the book. I was impressed that this text is particularly adept at explaining those areas in which