tbuckley/cabot-search huggingface dataset:
Recurrent Pneumococcal Meningitis
Authors: John P. Whitecar, Jack L. Reddin, Wesley W. Spink
Journal: New England Journal of Medicine (1966)

ALTHOUGH favorable results are obtained with penicillin in the therapy of pneumococcal meningitis this infection remains a serious disease. The mortality rate in patients forty years of age and over approximates 50 per cent. Whereas fatal cases are considerably less frequent in children, residual damage to the central nervous system is common and severe.The purpose of this report is to record a series of observations carried out over a period of several years on a patient who had had 11 different attacks of pneumococcal meningitis due to at least 5 different types of Diplococcus pneumoniae. Unusual features about . . .
Symptomatic Secondary Hormone Syndromes in Patients with Established Malignant Pancreatic Endocrine Tumors
Authors: David Wynick, Susan J. Williams, Stephen R. Bloom
Journal: New England Journal of Medicine (1988)

Over a five-year period, we measured concentrations of gut hormones in plasma samples from 353 patients in whom diagnoses of pancreatic endocrine tumors were subsequently confirmed. A median of 19 months (range, 7 to 120) after the initial diagnosis, 24 of these patients (6.8 percent) had elevated concentrations of other hormones in association with new clinical symptoms. In 13 of these patients (8 with glucagonomas, 3 with tumors secreting vasoactive intestinal polypeptide, and 2 with insulinomas), hypergastrinemia developed along with the clinical features of a gastrinoma; 5 patients died of gastrointestinal perforation or bleeding, apparently caused by this second tumor. We conclude that patients with pancreatic endocrine tumors, regardless of their initial clinical picture, require continued surveillance for new elevations of hormones. (N Engl J Med 1988; 319:605–7.)
Outcome in people with open spina bifida at age 35: prospective community based cohort study
Authors: G. M Hunt
Journal: BMJ (2003)

The introduction of the cerebrospinal fluid shunt led to a fourfold increase in survival of babies with open spina bifida in the United Kingdom. 1 In 1963 a prospective independent review was set up to record the results and implications of the new treatment. 2 3Such data are crucial to the dilemmas associated with termination of affected pregnancies or treatment at birth. 4 We investigated survival, disability, health, and lifestyles in a complete cohort of adults with spina bifida.
The McGill Journal of Medicine (MJM)
Authors: Gale Hansen Starich, Joan S. Zenan
Journal: JAMA (1997)

<i>The McGill Journal of Medicine (MJM)</i>serves as an international, peerreviewed journal comprised totally of student contributions. An independent organization run by students at McGill University in Montreal manages this unique medical journal.<i>MJM</i>clearly lists its commercial, academic, and private financial supporters. The journal strives to address the need for a publication that features work solely from students to "serve notice that they can make a difference in the research community." The intended readership consists of students, residents, scientists, and physicians around the world. Original research and review articles relevant to medicine form the major sections of<i>MJM</i>. Two unique features are "Crossroads" and "<i>MJM</i>Focus." "Crossroads" consists of articles addressing the interrelationships of the humanities and medicine. In "<i>MJM</i>Focus" a series of articles explores the clinical, scientific, and pathological features of a medical specialty. The manuscript review process has two distinct stages. Appointed student editors, whose names
Hematopoietic stem cell–targeted neonatal gene therapy reverses lethally progressive osteopetrosis in oc/oc mice
Authors: Maria K. Johansson, Teun J. de Vries, Ton Schoenmaker, Mats Ehinger, Ann C. M. Brun, Anders Fasth, Stefan Karlsson, Vincent Everts, Johan Richter
Journal: Blood (2007)
Abstract A86: SIRT1 regulates Rac1-GTPase activation via the guanine nucleotide exchange factor TIAM1
Authors: Madhurima Saxena, Samantha S. Dykes, Allison E. Wang, James A. Cardelli, Kevin Pruitt
Journal: Cancer Research (2013)

Abstract SIRT1 deacetylase is overexpressed in different types of cancers and we and a few others have described a role for SIRT1 in regulating cancer cell migration. Rho GTPases are classic regulators of cell motility and are known to aberrantly enhance cancer cell migration in response to several anomalous cues. We hypothesized that one of mechanisms employed by SIRT1 to regulate cell motility is through regulation of Rac1-GTPase activation. To address this we utilized two cancer cell lines, CFPAC-1 pancreatic and MDA-MB-231 breast cancer cells, as our model. A significant decrease was observed in active Rac1 (GTP-bound Rac1) levels, in a GST-PAK-binding domain pull-down assay, upon inhibition of SIRT1 by small molecule inhibitors or knockdown of SIRT1 by shRNA as compared to vehicle-treated or non-targeting shRNA transfected cells. Subsequent analysis revealed that SIRT1 co-immunoprecipitated with the Rac-guanine nucleotide exchange factor (GEF), TIAM1. To test whether TIAM1 is acetylated and if SIRT1 regulates its deacetylation we performed antibody-based pull-down of acetylated lysines from whole cell protein extracts and observed TIAM1 acetylation. Inhibition of deacetylase activity by small molecule inhibitors or overexpression of acetyltransferases caused an enhancement of acetylated TIAM1 signal. While a change in TIAM1 localization was not observed with SIRT1 knockdown, its ability to activate Rac1 was compromised. Several studies have demonstrated SIRT1's pro-tumorigenic potential. In this study we elucidate a mechanism by which SIRT1 regulates Rac-GTPase activation via TIAM1 acetylation. Controlling the “switch-mechanism” that the small GTPases utilize for inducing downstream activity can be crucial from a drug-development perspective. Our findings not only provide a new mechanism for regulation of Rac-GTPase activity but also emphasize SIRT1's potential as a targetable molecule in cancer. This work is supported by CA155223 and the graduate stipend for Madhurima Saxena is provided by a Carroll-Feist Pre-doctoral Fellowship awarded by the Feist-Weiller Cancer Center at LSU Health Shreveport, Shreveport, LA. Citation Format: Madhurima Saxena, Samantha S. Dykes, Allison E. Wang, James A. Cardelli2,3, Kevin Pruitt1,3. SIRT1 regulates Rac1-GTPase activation via the guanine nucleotide exchange factor TIAM1. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr A86.
Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients
Authors: A Wesołowska-Andersen, L Borst, M D Dalgaard, R Yadav, K K Rasmussen, P S Wehner, M Rasmussen, T F Ørntoft, I Nordentoft, R Koehler, C R Bartram, M Schrappe, T Sicheritz-Ponten, L Gautier, H Marquart, H O Madsen, S Brunak, M Stanulla, R Gupta, K Schmiegelow
Journal: Leukemia (2014)

Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10–15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant single-nucleotide polymorphisms (SNPs) to identify host genome profiles associated with relapse risk in 352 patients from the Nordic ALL92/2000 protocols and 426 patients from the German Berlin–Frankfurt–Munster (BFM) ALL2000 protocol. Patients were enrolled between 1992 and 2008 (median follow-up: 7.6 years). Eleven cross-validated SNPs were significantly associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates ranged from 4% (95% confidence interval (CI): 1.6–6.3%) for the best group (72% of patients) to 76% (95% CI: 41–90%) for the worst group (5% of patients, P<0.001). Validation of these findings and similar approaches to identify SNPs associated with toxicities may allow future individualized relapse and toxicity risk-based treatments adaptation.
Sugar Metabolism and Diabetes—A Question of Priority.
Authors: Alfred C. Croftan
Journal: JAMA (1904)

Chicago, Jan. 22, 1904. <h3>To the Editor:</h3> —In an able editorial published in a recent issue ofThe Journal(1903, p. 1480) you call attention to Cohnheim's discovery that the pancreas mixed with muscle tissue possesses the power of destroying sugar, and you properly emphasize the fundamental importance of this finding inasmuch as it aids in interpreting the rôle of the pancreas in sugar metabolism and diabetes. You also say, "Of course this does not preclude the possibility of a similar combined effect with substances in other tissues of the body where sugar is burned." As a matter of fact, another investigator, working simultaneously with Cohnheim, discovered that pancreas and liver combined also possessed sugar-destroying powers. You lay particular stress in this editorial on the fact that the pancreas alone, or the different tissues of the body alone, can not destroy sugar, whereas the addition of pancreas to different organs
Russia faces shortage of lifesaving drugs as rouble halves in value
Authors: J. Follett
Journal: BMJ (2015)

Russia’s economic crisis is hurting its health sector, putting severe pressure on spending and pushing up the prices of drugs, prompting cancer specialists to warn of possible shortages.

The rouble has lost about 50% of its value against the US dollar since the start of last year, making foreign made drugs more expensive. Russia imports over 70% of its drugs, and the rouble’s precipitous fall has prompted it to start buying less abroad and to …
Autoimmune Polyglandular Syndrome Type II Associated with Jejunal Gastrointestinal Stromal Tumor: Diagnosis by Capsule Endoscopy
Authors: M. Pennazio, A. Arrigoni, T. Sprujevnik, A. Bertone, M. Cavallero, M. Spandre, F. Calvo, M. Mineccia, E. Berardengo, G. Canavese, V. Alvisi
Journal: Endoscopy (2004)

A 49-year-old woman with autoimmune polyglandular syndrome type II (Addison’s disease and hypothyroidism) was referred to our department, as she was suffering from persistent iron-deficiency anemia and had positive results from fecal occult blood test. The history of bleeding was approximately 3 years during which period she had been treated with iron supplementation. Mean Hb concentration was 8.4 g/100 ml (range 6.1-11.7). Previous diagnostic investigations had included two esophagogastroduodenoscopies, two total colonoscopies, a 99Tc-labeled red cells scan, a 99Tc-pertechnetate scan, a small-bowel follow-through investigation, and a computed tomography (CT) scan. All these tests had failed to identify the source of bleeding.
Allergen specific immunotherapy attenuates early and late phase reactions in lower airways of birch pollen asthmatic patients: a double blind placebo‐controlled study<sup>1</sup>
Authors: M. B. Arvidsson, O. Löwhagen, S. Rak
Journal: Allergy (2003)

Background: Few placebo‐controlled studies have examined the effect of allergen specific immunotherapy (SIT) on early and late phase asthmatic reactions. In this placebo‐controlled study we have investigated the effect of 1 year of SIT with standardized birch pollen extract on early and late phase asthmatic reactions in adult asthmatic patients. Methods: Nineteen patients with a history of birch‐pollen‐induced seasonal symptoms from upper and lower airways, positive skin prick test and in vitro specific immunoglobulin E to birch pollen extract were included. Allergen and methacholine bronchial challenges were performed and blood samples obtained for analyses of total eosinophil count and eosinophil cationic protein (ECP) in serum, before and after 1 year of immunotherapy treatment. Results: All patients developed early and 16 of 19 both early and late phase asthmatic reactions. A significant increase in allergen dose was required to evoke early asthmatic reaction in the immunotherapy group ( P &lt; 0.01) after 1 year of treatment. The difference between the groups was significant ( P &lt; 0.01). Also the size of late asthmatic reaction was significantly reduced in the SIT group compared with placebo treated patients ( P &lt; 0.01). Twenty‐four hours after allergen challenge methacholine sensitivity, number of total eosinophils and ECP increased significantly in the placebo ( P &lt; 0.02, P &lt; 0.05 and P &lt; 0.05 respectively), but not in the SIT group. Conclusion: Allergen SIT with standardized birch pollen extract decreased early and late asthmatic responses following bronchial challenge in pollen allergic patients, thus confirming anti‐inflammatory effect of the treatment.
The eNOS cofactor tetrahydrobiopterin improves endothelial dysfunction in livers of rats with CCl4 cirrhosis
Authors: Vasilica Matei, Aina Rodríguez-Vilarrupla, Ramon Deulofeu, Dolors Colomer, Mercedes Fernández, Jaime Bosch, Juan-Carlos Garcia-Pagán
Journal: Hepatology (2006)

In cirrhosis, intrahepatic endothelial dysfunction is one of the mechanisms involved in the increased resistance to portal blood flow and therefore in the development of portal hypertension. Endothelial nitric oxide synthase (eNOS) uncoupling due to deficiency of tetrahydrobiopterin (BH4) results in decreased production of NO and plays a major role in endothelial dysfunction in other conditions. We examined whether eNOS uncoupling is involved in the pathogenesis of endothelial dysfunction of livers with cirrhosis. Basal levels of tetrahydrobiopterin and guanosine triphosphate (GTP)-cyclohydrolase (BH4 rate-limiting enzyme) expression and activity were determined in liver homogenates of control and rats with CCl4 cirrhosis. Thereafter, rats were treated with tetrahydrobiopterin, and eNOS activity, NO bioavailability, assessed with a functional assay, and the vasodilator response to acetylcholine (endothelial function) were evaluated. Livers with cirrhosis showed reduced BH4 levels and decreased GTP-cyclohydrolase activity and expression, which were associated with impaired vasorelaxation to acetylcholine. Tetrahydrobiopterin supplementation increased BH4 hepatic levels and eNOS activity and significantly improved the vasodilator response to acetylcholine in rats with cirrhosis. In conclusion, the impaired response to acetylcholine of livers with cirrhosis is modulated by a reduced availability of the eNOS cofactor, tetrahydrobiopterin. Tetrahydrobiopterin supplementation improved the endothelial dysfunction of cirrhotic livers.
Association of pre-intervention activated clotting times (ACT) and clinical outcomes following percutaneous coronary revascularization: Results from the IMPACT-II trial
Authors: Frank V. Aguirre, James J. Ferguson, James C. Blankenship, Karen S. Pieper, Marc Taylor, Robert A. Harrington, Michele Rund, Eugene A. Caracciolo, Thomas J. Donohue, Robert M. Califf, A.Michael Lincoff, James E. Tcheng, Eric J. Topol
Journal: Journal of the American College of Cardiology (1996)
B-Cell–Depleting Induction Therapy and Acute Cellular Rejection
Authors: Menna R. Clatworthy, Christopher J.E. Watson, Gemma Plotnek, Vicky Bardsley, Afzal N. Chaudhry, J. Andrew Bradley, Kenneth G.C. Smith
Journal: New England Journal of Medicine (2009)

To the Editor: B-cell depletion is an effective treatment for a number of autoimmune diseases in which B cells were not previously considered to be important, such as multiple sclerosis.1 In renal ...
TCT-632 Contemporary PCI Practices Across Three Continents: A Glimpse Into the Preliminary Results of e-NObori Study
Authors: Jawed Polad, Kristof Graf, Sanbaev Askhat Koishybaevich, Shih-Hung Chan, Martine Gilard, Sacha Grunert, Andres Iñiguez, Stefan James, M. Meuwissen, Luiz Alberto Piva Mattos
Journal: Journal of the American College of Cardiology (2012)
Drug-Review Deadlines and Safety Problems
Authors: Daniel Carpenter, Evan James Zucker, Jerry Avorn
Journal: New England Journal of Medicine (2008)

The Prescription Drug User Fee Act (PDUFA) imposes deadlines for the completion of drug reviews by the Food and Drug Administration (FDA). Critics have suggested that these deadlines may result in rushed approvals and the emergence of unanticipated safety problems once a product is in clinical use.
Interstitial pulmonary fibrosis: a new side effect of practolol.
Authors: T M Erwteman, M C Braat, W G van Aken
Journal: BMJ (1977)

propoxyphene on 25 and 26 January.He felt generally unwell and developed abdominal pain on 26 January similar to that he had suffered after taking Distalgesic.Th-associated biochemical changes are shown in the table.Neither his temperature nor his eosinophil count rose.Subsequent exposure to paracetamol was uneventful.He has remained well since stopping Distalgesic.
Trends in Systolic Blood Pressure in the Thousand Aviator Cohort over a Twenty-four-Year Period
Authors: ALBERT OBERMAN, NORMAN E. LANE, WILLIAM R. HARLAN, ASHTON GRAYBIEL, ROBERT E. MITCHELL
Journal: Circulation (1967)

A cohort of 1,056 normotensive, healthy, young men initially examined in 1940 at the mean age of 24 years was followed at three periodic intervals through 1964. The cohort demonstrated little rise in mean systolic blood pressure beyond age 35; a portion of this cohort showed no change of systolic blood pressure with age. If the men are classified by quintile according to systolic blood pressure in 1940, those men in the upper quintile tend to remain high; when classified by quintile in 1951, those men at the extremes maintained their relative position through 1964. Predictive utility of a systolic blood pressure may be a function of its actual level as well as the age of the individual. Two factors further influenced the systolic blood pressure of this cohort, namely, parental longevity and gain in weight. The significant effect of parental longevity became less important relative to gain in weight as time progressed and after 1940 affected primarily those men who had gained weight.
Right to die case goes to House of Lords
Authors: Clare Dyer
Journal: BMJ (2001)

A terminally ill woman with motor neurone disease will take her case for the right to die to the United Kingdom's highest court next week. The House of Lords agreed last week to hear an expedited plea by Diane Pretty for the right to commit suicide with the help of her husband of 25 years, Brian.

The law lords have listed the case for 14 and 15 November because Mrs Pretty, aged 42, from Luton may have only weeks …
Independence of Paget's Disease of Bone from Parathyroid Hormone.
Authors: Saul Genuth
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971Independence of Paget's Disease of Bone from Parathyroid Hormone.Saul Genuth, M.D., LeRoy Klein, M.D.Saul Genuth, M.D.Search for more papers by this author, LeRoy Klein, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-823_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThis report describes studies of two patients with disseminated Paget's disease of bone who presented a unique opportunity to observe the relationship between disease activity and parathyroid hormone (PTH) effects.Patient 1 had simultaneous idiopathic hypoparathyroidism. Basal studies showed serum calcium, 5.5 mg/100 ml (ionized 43%); serum phosphorus, 4.8 mg/100 ml; serum PTH, less than 0.2 ng/ml; alkaline phosphatase, 394 IU (normal, 15 to 45 IU); and urinary hydroxyproline, 240 to 260 mg/day (normal, less than 40). After administration of PTH, serum calcium rose to 11.2 mg/100 ml (49% ionized); serum phosphorus fell to 2.5 mg/100 ml, and urinary calcium... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cleveland, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 823-823KeywordsBoneCalciumHypoparathyroidismMetastasisParathyroid hormonePhosphatasesPhosphorus Issue Published: 1 May 1971 PDF downloadLoading ...
Abnormal haem biosynthesis in the chronic anaemia of rheumatoid arthritis.
Authors: T Houston, M Moore, D Porter, R Sturrock, E Fitzsimons
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--The chronic microcytic anaemia of rheumatoid arthritis (RA) occurs despite the presence of adequate reticulo-endothelial iron stores. The red cell microcytosis is evidence of impaired haemoglobin production. This study has examined possible abnormalities of erythroid haem biosynthesis that may contribute to the anaemia. METHODS--5-Aminolaevulinate (ALA) synthase and ferrochelatase activities were assayed in whole bone marrow and in purified erythroblasts from patients with RA and in control subjects. All patients were iron replete with demonstrable iron in the bone marrow. RESULTS--ALA synthase activity was significantly reduced in both whole bone marrow and purified erythroblasts from patients with the anaemia of RA. Erythrocyte protoporphyrin levels were raised in nine of 12 patients tested while ferrochelatase activity was normal. CONCLUSION--These abnormalities provide absolute evidence of abnormal erythroblast haem biosynthesis and iron metabolism in the anaemia of RA and most likely reflect decreased ALA synthase mRNA translation and some abnormality of erythroblast iron transport. Further studies using highly purified erythroblast populations will attempt to identify the causal factors leading to this abnormal erythroblast metabolism.
A Metastasis Caught in the Act
Authors: Daniel J. Brat, Ralph H. Hruban
Journal: New England Journal of Medicine (1996)

Figure 1. A 52-year-old man with no history of serious illness presented with abdominal pain, dark-colored urine, light-colored stools, and jaundice. Abdominal ultrasonography revealed dilatation of the intrahepatic and extrahepatic bile ducts. Surgical exploration and a pancreatoduodenectomy (Whipple's resection) were performed, revealing an infiltrating, poorly differentiated adenocarcinoma of the distal common bile duct. The carcinoma measured 2.0 cm in its greatest dimension. All margins of resection were negative for tumor. Fifteen lymph nodes were examined histologically for evidence of metastasis, and a single micrometastasis was identified (arrow). The carcinoma is present in sinusoids within the node and in a dilated . . .
Localized Colitis Cystica Profunda of the Sigmoid Colon
Authors: K. Yashiro, Y. Murakami, B. Iizuka, K. Hasegawa, K. Nagasako, A. Yamada
Journal: Endoscopy (1985)

Localized colitis cystica profunda (CCP) is a rare condition found in the rectum. Localized CCP of 70-year-old man was found in the sigmoid colon, it was accompanied by a cancer in the ascending colon and an adenomatous polyp with focal malignancy in the sigmoid colon. Colonoscopically, the tumor appeared like a submucosal tumor.