tbuckley/cabot-search huggingface dataset:
Rate of Protein Evolution Versus Fitness Effect of Gene Deletion
Authors: J. Yang
Journal: Molecular Biology and Evolution (2003)

Whether nonessential genes evolve faster than essential genes has been a controversial issue. To resolve this issue, we use the data from a nearly complete set of single-gene deletions in the yeast Saccharomyces cerevisiae to assess protein dispensability. Also, instead of the nematode, which was used previously but is only distantly related to S. cerevisiae, we use another yeast, Candida albicans, as a second species to estimate the evolutionary distances between orthologous genes in two species. Our analysis reveals only a weak correlation between protein dispensability and evolutionary rate. More important, the correlation disappears when duplicate genes are removed from the analysis. And surprisingly, the average rate of nonsynonymous substitution is considerably lower than that for single-copy genes in the yeast genome. This observation suggests that structural constraints are more important in determining the rate of evolution of a protein than dispensability because duplicate genes are on average more dispensable than single-copy genes. For duplicate genes, those with only a weak effect or no effect of deletion on fitness evolve on average faster than those with a moderate or strong effect of deletion on fitness, which in turn evolve on average faster than those with a lethal effect of deletion.
Atypical presentation of Churg-Strauss syndrome or an undescribed hypereosinophilic disease?
Authors: Emanuel Della-Torre, Moreno Tresoldi, Raffaella Scotti, Luisa Praderio, Renata Mellone, Maurilio Ponzoni, Claudio Doglioni, Maria Grazia Sabbadini
Journal: Journal of Allergy and Clinical Immunology (2011)
¬Assessing Immediate and Delayed Reactions in Children Presenting to an Allergy Clinic with a Suspected Allergy to Amoxicillin
Authors: Christopher Mill, Marie-Noel Primeau, Elaine J. Medoff, Christine Lejtenyi, Nofar Kimchi, Elena Netchiporouk, Alizee Dery, Moshe Ben-Shoshan
Journal: Journal of Allergy and Clinical Immunology (2015)
An 82-Year-Old Woman With Cataracts
Authors: Stephen A. Obstbaum
Journal: JAMA (1996)

Dr Delbanco: Mrs K is an 82-year-old widowed former seamstress with poor vision secondary to bilateral cataracts. She lives with her daughter and extended family in a suburb of Boston, Mass. In 1977 she came to the United States from Haiti. She receives her primary care at the Beth Israel Hospital from a general internist and a nurse practitioner, Ms M, and speaks only Haitian Creole. She has Medicare without supplemental insurance. Mrs K was first seen as a patient in 1977, and at that time she was found to have bilateral cataracts. She has complained of poor vision throughout the years and has sought help from a physician for her vision during some of her frequent trips back to Haiti. During 1 of these visits, she was given potassium iodide eyedrops. In the fall of 1995, Mrs K complained of blurriness and a clear watery discharge in her left
Helping Physicians Recognize Bedside Rationing
Authors: Anthony N. Galanos
Journal: Annals of Internal Medicine (1997)

Letters1 June 1997Helping Physicians Recognize Bedside RationingAnthony N. Galanos, MDAnthony N. Galanos, MDDuke University Medical Center, Durham, NC 27710Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-11-199706010-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Drs. Ubel and Goold [1] are to be applauded for helping physicians define and recognize when they are rationing at the bedside. Indeed, the medical literature reflects that silent rationing [2] and implicit rationing [3] have been and continue to be commonplace. My concern is that clinicians may not only ration without awareness but also execute their biases when they do so. Elderly persons, for example, are particularly vulnerable to this type of bedside rationing.Although we may know that the fastest-growing segment of our population is persons 85 years of age and older, it may not ...References1. Ubel PA, Goold S. Recognizing bedside rationing: clear cases and tough calls. Ann Intern Med. 1997; 126:74-80. Google Scholar2. Schwartz WB, Mendelson DN. Why managed care cannot contain hospital costs without rationing. Health Aff (Millwood). 1992; 11:100-7. Google Scholar3. Schroeder, SA. Rationing medical care-a comparative perspective. N Engl J Med. 1994; 331:1089-91. Google Scholar4. Callahan D. Setting Limits: Medical Goals in an Aging Society. New York: Simon and Schuster; 1987. Google Scholar5. Hamel MB, Phillips RS, Teno JM, Lynn J, Galanos AN, Davis RB, et al. Seriously ill hospitalized adults: do we spend less on older patients? J Am Geriatr Soc. 1996; 44:1043-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: Duke University Medical Center, Durham, NC 27710 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1997Volume 126, Issue 11Page: 921KeywordsAge groupsBehaviorElderlyHealth careSuicide Issue Published: 1 June 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Bochdalek Hernia, Incidental Finding on Sestamibi Parathyroid Scan
Authors: Shelley A. Quarless, Clinton N. Wells
Journal: Clinical Nuclear Medicine (2005)

A 65-year-old man with a history of a resected parathyroid adenoma in 1995 presented with laboratory studies concerning a recurrent parathyroid adenoma. A Tc-99m sestamibi parathyroid scan was performed.
Stress Ulcers — A Continuing Challenge
Authors: Ben Eiseman, Robert L. Heyman
Journal: New England Journal of Medicine (1970)

STRUCK by the frequency of stress ulcers in the severely injured combat casualty who, on top of his initial injury, may suffer some additional complication, the Committee on Trauma of the National Research Council recently held a conferencet of civilian and military experts on this subject in Washington, D.C. Their deliberations emphasized many areas of controversy and the inadequacy of both medical and surgical treatment (mortality of 35 to 65 per cent) of this lesion.†Supported by the Offices of the Surgeons General, Department of the Army and Department of the Navy (contract DADA 17–69-C-9084), and by the National Institutes . . .
PTU-065 Is There A Role For Faecal Calprotectin In The Investigation Of Diarrhoea In Patients With Hiv?
Authors: A Jeevagan, LM Clayton, S Soni, M Austin
Journal: Gut (2014)

<h3>Introduction</h3> Diarrhoea is the most common gastrointestinal symptom in patients with HIV. Faecal calprotectin (FCP) is a useful test in the investigation of chronic diarrhoea in the general population.<sup>1</sup> The sensitivity of this test in HIV-patients with chronic diarrhoea is unknown. <h3>Methods</h3> HIV-positive patients undergoing investigation for CD between January 2011 and August 2013 were identified. Demographics and clinical data including measurement of FCP and endoscopy findings were taken from the patients medical records <h3>Results</h3> 60 patients were referred by the HIV team to Gastroenterology clinic for investigation of CD. There were 55 (92%) males, mean age was 44 years. All were receiving antiretroviral therapy. No patients had a previous history of Inflammatory Bowel Disease (IBD), 59/60 had negative stool cultures. One patient was diagnosed with giardiasis and excluded from the study. Of the remaining, 54/59 (92%) patients had FCP measured, of which 36 (67%) demonstrated inflammation. Of these 31/36 (87%) patients with elevated FCP underwent lower GI endoscopy. 9/31 (30%) patients had abnormal macroscopic findings including mild non-specific inflammatory changes (4/31), polyps (2/31), threadworms (1/31) and ileitis (2/31). None had evidence of IBD. <h3>Conclusion</h3> In HIV positive individuals receiving antiretroviral therapy 30% patients with elevated FCP had macroscopic disease. No patients had a diagnosis of IBD. No cause beyond anti-retroviral medication was found. FCP is not a useful test to investigate chronic diarrhoea in this patient cohort. <h3>Reference</h3> Konikoff MR, Denson LA. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease. <i>Inflamm Bowel Dis</i>. 2006 Jun;12(6):524–34 <h3>Disclosure of Interest</h3> None Declared.
Cholecystectomy hazardous in patient with cirrhosis
Authors: Jaan Kangilaski
Journal: JAMA (1981)

Autopsies show that many patients with alcoholic liver disease also suffer from gallstones—but cholecystectomy in these patients is extremely dangerous.  Just how dangerous is shown by a retrospective study from the Hines (Ill) Veterans Administration Hospital and the Loyola University of Chicago Stritch School of Medicine that was reported at the New York meeting of the Society for the Surgery of the Alimentary Tract.  G. V. Aranha, MD, and co-workers studied the charts of 429 patients who had undergone elective or emergency cholecystectomy at the VA hospital between 1971 and 1979. Fifty-five of these patients were cirrhotic; the prothrombin times of 43 of them exceeded normal by less than 2.5 s, but the prothrombin times of 12 patients were even longer.  The postoperative mortality in the patients with the highest prothrombin rates was 83%—ten out of 12, the surgeon said. Mortality in the other cirrhotic patients was 9.3% (fourteen of
Prenatal Exposure to Polycyclic Aromatic Hydrocarbons, Benzo[ <i>a</i> ]pyrene–DNA Adducts, and Genomic DNA Methylation in Cord Blood
Authors: Julie B. Herbstman, Deliang Tang, Deguang Zhu, Lirong Qu, Andreas Sjödin, Zheng Li, David Camann, Frederica P. Perera
Journal: Environmental Health Perspectives (2012)

Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic environmental pollutants generated during incomplete combustion. After exposure and during metabolism, PAHs can form reactive epoxides that can covalently bind to DNA. These PAH-DNA adducts are established markers of cancer risk. PAH exposure has been associated with epigenetic alterations, including genomic cytosine methylation. Both global hypomethylation and hypermethylation of specific genes have been associated with cancer and other diseases in humans. Experimental evidence suggests that PAH-DNA adduct formation may preferentially target methylated genomic regions. Early embryonic development may be a particularly susceptible period for PAH exposure, resulting in both increased PAH-DNA adducts and altered DNA methylation.We explored whether prenatal exposure to PAHs is associated with genomic DNA methylation in cord blood and whether methylation levels are associated with the presence of detectable PAH-DNA adducts.In a longitudinal cohort study of nonsmoking women in New York City, we measured PAH exposure during pregnancy using personal air monitors, assessed PAH internal dose using prenatal urinary metabolites (in a subset), and quantified benzo[a]pyrene-DNA adducts and genomic DNA methylation in cord blood DNA among 164 participants.Prenatal PAH exposure was associated with lower global methylation in umbilical cord white blood cells (p = 0.05), but global methylation levels were positively associated with the presence of detectable adducts in cord blood (p = 0.01).These observations suggest that PAH exposure was adequate to alter global methylation in our study population. Additional epidemiologic studies that can measure site-specific cytosine methylation and adduct formation will improve our ability to understand this complex molecular pathway in vivo.
Doctors accepting flu vaccination is the sensible and responsible choice
Authors: J. Dunning, J. Nguyen-Van-Tam, K. Nicholson, P. Openshaw
Journal: BMJ (2011)

A ten-year-old intact male Rottweiler dog was examined for sudden onset of stranguria and pollakiuria. The dog had an intestinal lymphoma treated three years before with chemotherapy. Ultrasonographic examination of the abdomen showed a large dyshomogeneous prostate with an over-distended bladder. Cytological examination of the fine-needle aspirate from the prostate yielded a diagnosis of lymphoma. The diagnosis was confirmed by histopathological examination. The dog was treated with multi-drug chemotherapy and achieved a complete remission. The dog remained in complete remission for one year from the re-institution of chemotherapy before dying of recurrence. Lymphoma rarely invades the prostate in the dog. To the best of our knowledge this is the first report of prostatic recurrence of lymphoma in a canine patient originally affected by intestinal lymphoma and treated with chemotherapy.
Surgical bleeding: unexpected effect of a calcium antagonist
Authors: L E Wagenknecht, C D Furberg, J W Hammon, C Legault, B T Troost
Journal: BMJ (1995)

Calcium antagonists are among the most commonly used cardiovascular drugs. They have received regulatory approval for their antianginal and antihypertensive actions. While these agents provide appreciable improvement in symptoms in patients with angina pectoris, they have not yet been shown to prevent fatal and non-fatal cardiovascular events. Indeed, evidence suggests an adverse effect in survivors of myocardial infarction and in patients with angina.1

Speculation about a neuroprotective effect of calcium antagonists is based on the observation of an excessive influx of calcium at the time of neuronal death. This postulated mechanism, together with vasodilation, formed the theoretical basis for a clinical trial in patients undergoing replacement of a cardiac valve. It has been documented that patients placed on cardiopulmonary bypass are subject to arterial microemboli.2 The recognised clinical consequences of …
Motilin-induced gastric contractions signal hunger in man
Authors: J Tack, E Deloose, D Ang, E Scarpellini, T Vanuytsel, L Van Oudenhove, I Depoortere
Journal: Gut (2014)

<h3>Rationale</h3> Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin. <h3>Objectives</h3> To study the relationship between hunger and MMC phases (I–III), focusing on spontaneous and pharmacologically induced phase III and the correlation with plasma motilin and ghrelin levels. The role of phase III was also studied in the return of hunger after a meal in healthy individuals and in patients with loss of appetite. <h3>Findings</h3> In fasting healthy volunteers, mean hunger ratings during a gastric (62.5±7.5) but not a duodenal (40.4±5.4) phase III were higher (p&lt;0.0005) than during phase I (27.4±4.7) and phase II (37±4.5). The motilin agonist erythromycin, but not the cholinesterase inhibitor neostigmine, induced a premature gastric phase III, which coincided with an increase in hunger scores from 29.2±7 to 61.7±8. The somatostatin analogue octreotide induced a premature intestinal phase III without a rise in hunger scores. Hunger ratings significantly correlated (β=0.05; p=0.01) with motilin plasma levels, and this relationship was lost after erythromycin administration. Motilin, but not ghrelin administration, induced a premature gastric phase III and a rise in hunger scores. In contrast to octreotide, postprandial administration of erythromycin induced a premature gastric phase III accompanied by an early rise in hunger ratings. In patients with unexplained loss of appetite, gastric phase III was absent and hunger ratings were lower. <h3>Conclusions</h3> Motilin-induced gastric phase III is a hunger signal from GIT in man.
<i>Haemophilus influenzae</i>Meningitis
Authors: Joel I. Ward, David W. Fraser, Larry J. Baraff, Brian D. Plikaytis
Journal: New England Journal of Medicine (1979)

To determine the risk of severe Haemophilus influenzae illness among household contacts of patients with H. influenzae meningitis, we studied prospective data obtained in 19 states from January 1, 1977, to June 30, 1978. H. influenzae meningitis was reported in 1403 patients, and 1147 (82 per cent) of the exposed families were investigated for the occurrence of H. influenzae disease within 30 days after its onset in the index patient. During this interval, nine of 1687 household contacts (0.5 per cent) under the age of six years had systemic disease confirmed to be caused by H. influenzae Type b. The risk in children less than one year of age was 6 per cent, and the risk in those less than four years of age was 2.1 per cent. None of 2624 contacts above the age of five was affected. In the 30 days after onset of meningitis, the risk of this infection alone, aside from other types of serious H. influenzae disease, is 585 times greater in household contacts than the age-adjusted risk in the general population. The risk of H. influenzae disease in household contacts under six years of age is similar to the risk of secondary meningococcal disease in all household contacts--indicating a need for effective antimicrobial prophylaxis.
From the Curator's Notebook
Authors: Walter G. Phippen
Journal: New England Journal of Medicine (1959)

AN ADVENTURE IN CO-OPERATIONAs president emeritus of the Boston Medical Library, I have had the privilege of continuing to attend the meetings of the Library's Board of Trustees. Thus, I have been able to witness at close range the steps by which the Trustees first explored, then negotiated, and finally agreed upon a plan for joining hands with the Harvard Medical School to operate a collaborative library service in a new building soon to be erected.The statesmanlike way in which the officers and committees of the Boston Medical Library and of Harvard conducted the negotiations and the excellent . . .
Exaggerated postural vasoconstrictor reflex in Raynaud's phenomenon.
Authors: N Olsen, O U Petring, N Rossing
Journal: BMJ (1987)

The central and local regulation of capillary blood flow in the finger was studied by the local xenon-133 washout technique in women with primary Raynaud9s phenomenon, men with vibration induced white finger, and their respective sex matched controls. The vasoconstrictor response to venous stasis of 40 mm Hg elicited by local reflex was normal in both types of Raynaud9s phenomenon. Change in posture from lying to sitting induced vasoconstriction in all groups, which was abolished by proximal nervous blockade. The vasoconstrictor response to sitting was augmented in both groups of subjects with Raynaud9s phenomenon compared with their sex matched controls. These results show the existence of central and local postural vasoconstrictor reflexes in normal fingers. In both types of Raynaud9s phenomenon there was hyperreactivity of the central sympathetic nervous system to orthostatic stress and normal function of digital arterioles and postganglionic sympathetic nerve fibres.
Oral and Intravenous Administration of Alcohol and the Pancreas
Authors: Gordon F. Madding
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Of the clinical varieties of chronic pancreatitis, that associated with alcoholism presents the most difficult problem in therapy. From the reported work one cannot conclude whether the alcohol exerts its effect by direct action on the duodenal mucosa or whether it acts by absorption into the blood stream and secondarily involves the pancreas. Lowenfels et al<sup>1</sup>demonstrated an increase in both the volume and amylase content of the pancreatic fluid after the intravenous injection of alcohol. Gizelt<sup>2</sup>believed the action of alcohol to be the summation of direct stimulation of the gland by the absorbed drug, direct stimulation of secretin in the duodenum, and an indirect stimulation of secretin secondary to alcohol induced acid production in the stomach. Dreiling et al<sup>3</sup>demonstrated that intravenous administration of alcohol neither stimulated the pancreas nor had a deleterious effect on patients with or without pancreatitis. Brooks and
Anaphylactic Shock in Dogs
Authors: Nathan Back
Journal: JAMA (1963)

THE ROLE of the fibrinolysin system in conditions associated with shock is complex and poorly understood. Increased fibrinolysis has been reported in anaphylactic shock,1major operations,2obstetrical accidents and hemorrhage,3and sudden death.4A recent review5suggests that the initial reaction in certain types of shock is activation of a protease system and subsequent formation or release or both of vasoactive polypeptides capable of stimulating activity of smooth muscle. These polypeptides, existing in the form of precursors in the systemic circulation and in various tissues, have been termed kinins and are reported to be released during peptone and anaphylactic shock.6  Despite reports of the appearance of fibrinolysis and kinin in shock states, there is no convincing evidence that their appearance is interrelated and involved in the pathogenesis of shock. It has been shown that the fibrinolytic enzyme plasmin, when given by rapid intravenous injection
Glutathione peroxidase 7 prevents cancer in the oesophagus
Authors: Maikel P Peppelenbosch, Manon C W Spaander, Marco J Bruno
Journal: Gut (2013)

Oesophageal cancer is the most rapidly increasing gastrointestinal cancer in the Western world with an increase of around 5% per annum. Surgical resection is considered the cornerstone in oesophageal cancer treatment with curative intent. The prognosis of oesophageal cancer has improved in patients eligible to undergo surgical resection, with 5-year survival rates ranging from 6% to 50%, but rarely exceeding 30%.1 ,2 When resection is not possible, prognosis of disease is truly infaust; patients rarely survive a year. The combination of rapid increase of incidence of oesophageal cancer with the inadequacy of the current therapeutic regimens urgently calls for the development of novel prevention and treatment modalities. Rational design of such treatment is, however, hampered by lack of knowledge of the mechanisms operative in the oesophagus that constitute the rate-limiting steps in the initiation and further degeneration of oesophageal malignancy.

Generally, oesophageal cancer can either manifest itself in a squamous form or derive from the Barrett's oesophagus precursor lesion and form adenocarcinoma.3 Most progress in the treatment has been made with respect to the former form …