tbuckley/cabot-search huggingface dataset:
Do engineered natriuretic peptides have greater therapeutic potential than do native peptides?
Authors: A. H. L. From
Journal: Cardiovascular Research (2010)

This editorial refers to ‘A novel chimeric natriuretic peptide reduces cardiomyocyte hypertrophy through the NHE-1–calcineurin pathway’ by A. Kilic et al. , doi:10.1093/cvr/cvq254. 

As is well known, intravenously infused nesiritide [a recombinant form of brain-type natriuretic peptide (BNP)] antagonizes renin–angiotensin–aldosterone system activation and induces natriuresis, diuresis, and venous and arterial dilation. When administered to patients with acutely decompensated heart failure, a rapid reduction of pulmonary capillary pressure and consequent relief of dyspnoea often results. However, BNP-induced dilation of resistance (arterioles) and capacitance (veins) vessels taken together with the diuresis-associated reduction of blood (plasma) volume causes clinically significant systemic hypotension in some patients. Unfortunately, this hypotension can be associated with decreased renal perfusion and worsening of renal function, and the latter has been associated with increased morbidity and mortality in some clinical trials.1 The hypotension and consequent complications can be attenuated by reducing the dose of nesiritide being administered.1

Recently, Burnett and colleagues speculated that they might be able to improve the therapeutic properties of natriuretic peptides by modifying their structures. Their goal was to generate a natriuretic peptide that retained the biological activities of BNP sans the capacity to dilate resistance vessels. Their first engineered chimeric natriuretic peptide (CD-NP) comprised the 15-amino acid C-terminus of the Dendroaspis peptide (a snake-derived natriuretic peptide) and the peptide ring component of the cardiac-type natriuretic peptide (CNP). CNP lacks renal actions but retains veno-dilator capacity and has only modest dilatory effects … 

*Corresponding author. Tel: +1 612 626 2001; fax: +1 612 626 2004, Email: fromx001{at}umn.edu
<i>KRAS</i> Mutation Is Associated with Lung Metastasis in Patients with Curatively Resected Colorectal Cancer
Authors: Jeanne Tie, Lara Lipton, Jayesh Desai, Peter Gibbs, Robert N. Jorissen, Michael Christie, Katharine J. Drummond, Benjamin N.J. Thomson, Valery Usatoff, Peter M. Evans, Adrian W. Pick, Simon Knight, Peter W.G. Carne, Roger Berry, Adrian Polglase, Paul McMurrick, Qi Zhao, Dana Busam, Robert L. Strausberg, Enric Domingo, Ian P.M. Tomlinson, Rachel Midgley, David Kerr, Oliver M. Sieber
Journal: Clinical Cancer Research (2011)

Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse.One hundred colorectal cancer metastases were screened for mutations in 19 oncogenes, and further 61 metastases and 87 matched primary cancers were analyzed for genes with identified mutations. Mutation prevalence was compared between (a) metastases from liver (n = 65), lung (n = 50), and brain (n = 46), (b) metastases and matched primary cancers, and (c) metastases and an independent cohort of primary cancers (n = 604). Mutations differing between metastasis sites were evaluated as markers for site of relapse in 859 patients from the VICTOR trial.In colorectal cancer metastases, mutations were detected in 4 of 19 oncogenes: BRAF (3.1%), KRAS (48.4%), NRAS (6.2%), and PIK3CA (16.1%). KRAS mutation prevalence was significantly higher in lung (62.0%) and brain (56.5%) than in liver metastases (32.3%; P = 0.003). Mutation status was highly concordant between primary cancer and metastasis from the same individual. Compared with independent primary cancers, KRAS mutations were more common in lung and brain metastases (P < 0.005), but similar in liver metastases. Correspondingly, KRAS mutation was associated with lung relapse (HR = 2.1; 95% CI, 1.2 to 3.5, P = 0.007) but not liver relapse in patients from the VICTOR trial.KRAS mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients. Our data highlight the potential of somatic mutations for informing surveillance strategies.
Primer on Certain Elements of Medical Decision Making
Authors: B J McNeil, E Keller, S J Adelstein
Journal: New England Journal of Medicine (1975)

The value of a diagnostic test lies in its ability to detect patients with disease (its sensitivity) and to exclude patients without disease (its specificity). For tests with binary outcomes, these measures are fixed. For tests with a continuous scale of values, various cutoff points can be selected to adjust the sensitivity and specificity of the test to conform with the physician's goals. Principles of statistical decision theory and information theory suggest technics for objectively determining these cutoff points, depending upon whether the physician is concerned with health costs, with financial costs, or with the information content of the test.
Health effects of environmental exposure to cadmium: objectives, design and organization of the cadmibel study: a cross-sectional morbidity study carried out in Belgium from 1985 to 1989
Authors: Robert Lauwerys, Antoon Amery, Alfred Bernard, Pierre Bruaux, Jean-Pierre Buchet, Françoise Claeys, Pierre De Plaen, Geneviève Ducoffre, Robert Fagard, Paul Lijnen, Laurence Nick, Harry Roels, Désiré Rondia, Annie Saint-Remy, Francis Sartor, Jan Staessen
Journal: Environmental Health Perspectives (1990)

Cadmium is a cumulative environmental pollutant. For the general population mainly exposed by the oral route and through tobacco smoke inhalation, the kidney is the critical organ. Belgium is the principal producer of cadmium in Europe, and certain areas of the country are polluted by cadmium mainly because of past emissions from nonferrous industries. Preliminary studies carried out in one polluted area have suggested that environmental pollution might lead to an increased uptake of cadmium by the human body and possibly to health effects. Thus, a large-scale morbidity study has been initiated to assess the validity of this hypothesis. The present paper describes the protocol of this study. Its main objectives are to determine to what extent environmental exposure to cadmium resulting from industrial emissions may lead to accumulation of the metal in the human organism; to establish whether or not environmental exposure may induce renal changes and/or influence blood pressure; and to assess the acceptable internal dose of cadmium for the general population. The study design takes advantage of the fact that biological indicators of exposure, body burden, and early nephrotoxic effects of cadmium are available, which increase the likelihood of detecting a cause-effect relationship.
Antiarrhythmic drug effect mimicked by spontaneous variability of ventricular ectopy.
Authors: R A Winkle
Journal: Circulation (1978)

Twenty patients with frequent ventricular ectopic beats had a 5 1/2 hour ECG rhythm strip recorded. Individual patients showed a marked spontaneous variability from one half-hour to the next in the total number of ectopic beats (-99% to +1100%) and the occurrence of pairs or salvos. Although no patient received antiarrhythmic drugs, some patients showed a spontaneous change in arrhythmia which mimicked either drug suppression or drug-induced worsening of arrhythmias. If an antiarrhythmic drug had been given to these patients after the first half-hour, 65% would have been termed "drug responders," using the criteria of 50% reduction in ectopic beats and elimination of pairs or salvos during any half-hour period in the subsequent three hours. Spontaneous variability in ventricular ectopic beats causes serious problems when using ECG monitoring to evaluate antiarrhythmic drug response in individual patients. The arrhythmias averaged for the entire group remained stable during the recording period. Evaluating antiarrhythmic drugs by examining group response rather than individual patient response minimizes the effect of spontaneous variability.
Contempo '81. Neurology
Authors: D. J. Dalessio
Journal: JAMA (1981)

<h3>'Drug Holidays' and Parkinson's Disease</h3> A major advance in neurological therapeutics has been achieved in the last decade, using a regimen of levodopa or a combination of levodopa and carbidopa in Parkinson's disease.<sup>1,2</sup>Almost all patients with Parkinson's disease will respond in some degree to these drugs. With time, however, usually in three to six years, the effects of long-term levodopa therapy may become blunted.<sup>2-4</sup>Furthermore, the incidence of levodopa-induced side effects progressively increases. For example, after five years, 40% to 80% of patients with Parkinson's disease taking these medications will demonstrate dyskinesias.<sup>5</sup>Alterations in motor skills become common. Sudden changes from dyskinesias to akinesia (the on-off phenomenon) are well described.<sup>6</sup>Psychiatric symptoms of a toxic confusional type may occur, especially in the elderly.<sup>7</sup>Myoclonus and dystonias have been reported as well.<sup>8,9</sup>It is suggested that these side effects are related to alterations in
Evaluation of factor VIII pharmacokinetics in hemophilia‐A subjects undergoing surgery and description of a nomogram for dosing calculations
Authors: G. Longo, A. Messori, M. Morfini, F. Baudo, N. Ciavarella, S. Cinotti, E. Filimberti, G. Giustarini, A. C. Molinari, Pierluigi Rossi Ferrini
Journal: American Journal of Hematology (1989)

Abstract The pharmacokinetics of factor VIII were studied in a series of 20 hemophilia‐A patients undergoing surgery. Regardless of the type of operation, elimination of factor VIII was shown to be increased only in ten cases (50%) during the post‐operative period. In this subgroup of patients, factor VIII half‐life, measured immediately after surgery, was considerably shorter (mean = 9.6 hr, n = 10) than that determined in the same individual during the late operative period (mean = 17.8 hr, n = 10). These findings indicate that identification of patients with increased postoperative consumption of factor VIII can be of value in reducing the risk of hemorrhage in these subjects and in exposing other subjects with no postoperative increase in factor VIII clearance to less of the deficient factor. Data from 20 subjects were analyzed to construct a nomogram allowing individualized prediction of factor VIII dosing requirements. The nomogram, which is based on the “single point after a single dose” method, uses a value of factor VIII concentration measured at 10 hr after preoperative loading dose to predict the regimen producing the desired average steady‐state concentration of factor VIII (30, 60, or 90 units/dl).
Acute Bacterial Sinusitis
Authors: Jay F. Piccirillo
Journal: New England Journal of Medicine (2004)

A 43-year-old man has a two-week history of nasal congestion, postnasal drip, and fatigue. He has used an over-the-counter nasal decongestant and acetaminophen, without relief. During the past few days, facial pain and pressure have developed and have not responded to decongestants. In addition, his nasal discharge has turned from clear to yellow. How should he be treated?
Maprotiline hydrochloride and grand-mal seizures.
Authors: D Burley, A Jukes, J Steen
Journal: BMJ (1978)

discrepancies turn out to be mainly aberrations which are correctable in their wider context.Over the years death certification has improved with advances in medicine.More information is given and it is more precise.We should tackle administrative weaknesses such as failure of pathologists to state explicitly causes of death, failure to update after necropsy, and relegation of completion to junior doctors without instruction.Over the past 140 years these records (the results of everyday experience of doctors) have contributed a great deal to our knowledge of the health of the nation and to medical research.Of course, there is a continuous need to study their flaws -especially as part of practical research-as was done in the papers by the study group of the Royal College of Physicians.I trust that these papers will be read constructively, otherwise they may have a negative effect, the best becoming the enemy of the good.
Myosin isozymes in rabbit and human smooth muscles.
Authors: M J Lema, E D Pagani, R Shemin, F J Julian
Journal: Circulation Research (1986)

Although multiple forms of myosin in cardiac and skeletal muscles have been identified, it has not been firmly established that myosin isozymes are present in adult smooth muscle. Myosin, extracted from human thoracic aorta and lower saphenous vein and rabbit aorta and uterus, was analyzed by pyrophosphate gel electrophoresis to determine if myosin isozymes are present in these tissues. In all smooth muscle tissues studied, two myosin isozymes were detected and labelled as smooth muscle 1 and smooth muscle 2, smooth muscle 2 being the faster migrating isozyme. Bovine cultured smooth muscle cells from the media of thoracic aorta also contained two forms of myosin. However, cultured fibroblasts contained only one form of myosin. Extracting myosin from either relaxed or contracting rabbit aortic smooth muscle did not influence the mobilities of smooth muscle 1 and smooth muscle 2 on pyrophosphate gels, suggesting that the degree of light chain phosphorylation did not significantly alter the electrophoretic mobility under our conditions. Smooth muscle 1 and smooth muscle 2 myosins each contain heavy chains (200,000 daltons) and light chains (20,000 and 17,000 daltons) in addition to filamin (235,000 daltons), which is closely associated with the native protein. Myosin peptide maps of rabbit aorta and uterus revealed areas of substantially different banding patterns between smooth muscle 1 and smooth muscle 2 from the same tissue. Similar peptide maps of smooth muscle 1 bands were produced from the different tissues, but the smooth muscle 2 maps were dissimilar.(ABSTRACT TRUNCATED AT 250 WORDS)
Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase
Authors: Reuven Or, Michael Y. Shapira, Igor Resnick, Avraham Amar, Aliza Ackerstein, Simcha Samuel, Memet Aker, Elizabeth Naparstek, Arnon Nagler, Shimon Slavin
Journal: Blood (2002)
ANESTHETIC PROBLEMS IN HORMONAL DISORDERS OF THE ADRENAL GLANDS
Authors: E. M. Papper
Journal: JAMA (1952)

The number of patients afflicted with recognized disorders of the adrenal glands is obviously small. Even smaller at present is the number with adrenal disturbances who are candidates for surgical treatment. As knowledge, including improved diagnostic measures, concerning these disease processes is developed, operative intervention will probably be increased in scope and frequency in the care of these patients. However, the statistical incidence of these diseases in no way reflects the interest or importance of the adrenal glands in clinical medicine and surgery. These small glands exercise widespread influence on many physiological adjustments of the body to the environment. Studies have demonstrated some of the effects of the adrenals on circulation,<sup>1</sup>electrolyte metabolism,<sup>2</sup>renal function,<sup>3</sup>carbohydrate metabolism,<sup>4</sup>and other endocrine organs.<sup>5</sup>Recently there has been extensive interest and speculation on the relationship of adrenal activity to a large variety of apparently unrelated diseases and environmental
Analysis of RNA transcripts for HLA class II genes in human small intestinal biopsies.
Authors: B A Volk, D A Brenner, M F Kagnoff
Journal: Gut (1989)

Studies of the expression of selected genes within the intestinal mucosa will provide important new information about physiologic pathological processes that effect mucosal growth, differentiation, and function. To study gene expression in the gut, we developed a method to obtain sufficient undegraded RNA from human endoscopic intestinal biopsy specimens for Northern and slot blot analysis. To verify the method, we examined the differential expression of HLA class II genes in small intestinal mucosa. Levels of RNA transcripts for HLA-DR, -DP, and -DQ alpha and beta chains were assessed in freshly isolated endoscopic intestinal mucosal biopsy specimens and compared with levels in Epstein-Barr virus transformed B cells from the same individuals. Sufficient undegraded cellular RNA with distinct 28S and 18S ribosomal bands could be obtained from as few as two 2-3 mm endoscopic biopsies. Using chain and locus specific cDNA probes, HLA-DR, -DP, and -DQ subregion genes were shown to be expressed in intestinal mucosa, with the relative magnitude of RNA transcripts being DR greater than DP greater than DQ. The same hierarchy of expression was seen for EBV-transformed B cell lines. This method, in conjunction with the polymerase chain reaction for amplifying specific RNA transcripts and in situ hybridisation methods for the cellular localisation of RNA transcripts, will enable studies on the regulation of gene expression in the intestinal mucosa.
Effect of Nitroglycerin and Dipyridamole on Regional Coronary Resistance
Authors: WADIE M. FAM, MAURICE MCGREGOR
Journal: Circulation Research (1968)

We studied the changes caused by intravenous injection of nitroglycerin (0.3 to 0.6 mg) and dipyridamole (5 to 10 mg) on the resistance of large and small coronary arteries of dogs. The direction of change in resistance of large conductive vessels (R c ) was estimated by dividing the pressure drop from aorta to a superficial branch by the flow in that vessel. The total resistance (R t ) in the same vessel was estimated by relating aortic pressure to the same flow. The effects of both drugs on aortic pressure were comparable 3 to 7 minutes after injection. Nitroglycerin during this period caused a reduction in R c , whereas dipyridamole caused a significant reduction in R t for 12 minutes but no consistent changes in R c . In the same preparation, small intracoronary doses of the drugs, which hardly affected the aortic pressure, caused comparable changes in resistance. This was also evident in a preparation in which the flow in the coronary vessel was held constant. These two drugs therefore differ in their site of action on the coronary vascular bed, a difference which may explain their contrasting therapeutic effects in chronic coronary disease in man.
Depression of Muscle Protein Synthesis (MPS) with no Evidence of Elevated Muscle Protein Breakdown (MPB) Precedes Minor Muscle Wasting in Early Colorectal Cancer
Authors: S.M. Nyasavajjala, C. Srinath, S. Liptrot, A. Selby, D. Rankin, P. Atherton, K. Smith, J.P. Williams, J.N. Lund, R. Singh, M.J. Rennie
Journal: International Journal of Surgery (2010)
181 MMP-2 CT/TT GENOTYPE IS A RISK FACTOR FOR PATIENT MORTALITY OR ORTHOTOPIC LIVER TRANSPLANTATION IN PRIMARY SCLEROSING CHOLANGITIS
Authors: K. Sebib Korkmaz, B.-J.F. de Rooij, B. van Hoek, M. Janse, M.J. Coenraad, J.J. van der Reijden, R.K. Weersma, R.J. Porte, A.G. Baranski, H.W. Verspaget
Journal: Journal of Hepatology (2013)
UDCA, PBC, and biochemistry, what does normal mean?
Authors: M LEUSCHNER
Journal: Gut (2000)

Editor,—We read the commentary by Lindor ((2000) Gut 46:8–8.[OpenUrl][1][Abstract/FREE Full Text][2]) with great interest and would like to raise the following points. Lindor is not surprised that in our study1 patients with primary biliary cirrhosis (PBC) who initially had less abnormal liver function tests responded more favourably to ursodeoxycholic acid (UDCA) than those who had initially greater abnormal liver function values. We believe this is interesting as it is known that patients with lower abnormal liver function tests respond less favourably (for example, chronic autoimmune hepatitis to treatment with glucocorticoids) and that values do not decrease in a linear manner. Furthermore, it is well known that UDCA in PBC does not cause normalisation of liver function tests in most patients, and to date there has been no extensive examination of full and incomplete responders. Only in one study was this area addressed but few liver parameters were studied and there was only a short follow up period.2 Lindor states that our finding of no correlation between the percentage … [1]: {openurl}?query=rft.jtitle%253DGut%26rft.stitle%253DGut%26rft.aulast%253DLeuschner%26rft.auinit1%253DM%26rft.volume%253D46%26rft.issue%253D1%26rft.spage%253D121%26rft.epage%253D126%26rft.atitle%253DCharacterisation%2Bof%2Bpatients%2Bwith%2Bprimary%2Bbiliary%2Bcirrhosis%2Bresponding%2Bto%2Blong%2Bterm%2Bursodeoxycholic%2Bacid%2Btreatment%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fgut.46.1.121%26rft_id%253Dinfo%253Apmid%252F10601067%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=gutjnl&resid=46/1/121&atom=%2Fgutjnl%2F47%2F4%2F595.2.atom
Injection of Nonvariceal Bleeding Lesions of the Upper Gastrointestinal Tract
Authors: N. Soehendra, H. Grimm, M. Stenzel
Journal: Endoscopy (1985)

In a prospective series 102 non-variceal upper GI bleeders were studied. An indication for endoscopic injection therapy was seen in 63 patients. In accordance with bleeding intensity, 27 patients were grouped as Forrest Ia, 37 as Forrest Ib, 8 as Forrest II with a "visible vessel" and 13 as Forrest II without one. Definitive hemostasis was achieved in almost 100% of the cases. Within the Forrest Ia group mortality was lowered to 11% as compared with 20% within the emergency surgery group. More than 80% of patients had at least one severe coexistent illness. The aim of endoscopic injection is to avoid surgery in high-risk patients.
An Intervention to Reduce Residential Insecticide Exposure during Pregnancy among an Inner-City Cohort
Authors: Megan K. Williams, Dana B. Barr, David E. Camann, Linda A. Cruz, Elizabeth J. Carlton, Mejico Borjas, Andria Reyes, Dave Evans, Patrick L. Kinney, Ralph D. Whitehead, Frederica P. Perera, Stephen Matsoanne, Robin M. Whyatt
Journal: Environmental Health Perspectives (2006)

We previously reported widespread insecticide exposure during pregnancy among inner-city women from New York City. Here we report on a pilot intervention using integrated pest management (IPM) to reduce pest infestations and residential insecticide exposures among pregnant New York City African-American and Latina women (25 intervention and 27 control homes).The IPM consisted of professional cleaning, sealing of pest entry points, application of low-toxicity pesticides, and education. Cockroach infestation levels and 2-week integrated indoor air samples were collected at baseline and one month postintervention. The insecticides detected in the indoor air samples were also measured in maternal and umbilical cord blood collected at delivery.Cockroach infestations decreased significantly (p = 0.016) after the intervention among intervention cases but not control households. Among the intervention group, levels of piperonyl butoxide (a pyrethroid synergist) were significantly lower in indoor air samples after the intervention (p = 0.016). Insecticides were detected in maternal blood samples collected at delivery from controls but not from the intervention group. The difference was significant for trans-permethrin (p = 0.008) and of borderline significance (p = 0.1) for cis-permethrin and 2-isopropoxyphenol (a propoxur metabolite).To our knowledge, this is the first study to use biologic dosimeters of prenatal pesticide exposure for assessing effectiveness of IPM. These pilot data suggest that IPM is an effective strategy for reducing pest infestation levels and the internal dose of insecticides during pregnancy.
CONCENTRIC LEFT VENTRICULAR HYPERTROPHY AS INDEPENDENT PREDICTOR OF 1-YEAR REHOSPITALIZATION AND MORTALITY IN PATIENTS HOSPITALIZED FOR ACUTE HEART FAILURE AND PRESERVED EJECTION FRACTION
Authors: Liang Zhong, Yee How Lau, Ling Ling Sim, David Sim, Bernard Kwok, Terrance Chua, Raymond Lee, Ru-San Tan
Journal: Journal of the American College of Cardiology (2012)