tbuckley/cabot-search huggingface dataset:
Nilotinib and MEK Inhibitors Induce Synthetic Lethality through Paradoxical Activation of RAF in Drug-Resistant Chronic Myeloid Leukemia
Authors: Leisl M. Packer, Sareena Rana, Robert Hayward, Thomas O'Hare, Christopher A. Eide, Ana Rebocho, Sonja Heidorn, Matthew S. Zabriskie, Ion Niculescu-Duvaz, Brian J. Druker, Caroline Springer, Richard Marais
Journal: Cancer Cell (2011)
DISORDERED REGULATION OF TRAFFIC IN THE GUT
Authors: F. C. Eve
Journal: BMJ (1933)

This suggested excretory function of Brunner's glands is not entirely an original line of thought.In 1842 Curling, describing duodenal ulceration after burns, ex-.ressed a belief that " the duodenal glands of Brunner sympathized and compensated for the suppression of the exhalation from the skin by an increased activity."This, he theorized, " leads to an irritation which causes inflammation and ulceration."However, the role of I3runner's glands suggested by us remains in effect still a virgin field for investigation.There appears as yet to be no experimental evidence of any excretory function of these glands, and research on this point might throw much light upon the contentious field of proto-duodenitis and duodenal ulcer.SUMMARY1.The proto-duodenum is an especially vulnerable part of the intestinal tract owing to the presence of the fragile Brunner's glands.2. In cases of gastro-enteroptosis, where there is angulation at the duodeno-jejunal flexure sufficient to cause partial block, an inflammatory reaction may be produced by the presence of an irritant bile and acid mixture in the proto-duodenum.3. Brunner's glands may become inflamed during the excretion of certain toxins.
Allergy to beer in <scp>LTP</scp>‐sensitized patients: beers are not all the same
Authors: O. Quercia, G. Zoccatelli, G. F. Stefanini, G. Mistrello, S. Amato, M. Bolla, F. Emiliani, R. Asero
Journal: Allergy (2012)

Abstract Background Most cases of beer allergy reported so far have been associated with hypersensitivity to the non‐specific lipid transfer protein ( LTP ). In view of the marked differences in brewing processes we assessed IgE reactivity as well as tolerance to many different beers in an allergic patient. Methods A 45 year‐old man hypersensitive to grass pollen, cat dander and A lternaria tenuis with a history of urticaria and dyspnoea after drinking beer and a weak skin reactivity to commercial corn extract was studied. The patient underwent SPT with 36 different brands of beer and an open challenge with those scoring negative was performed. An immunoblot analysis was carried out using 2 SPT ‐positive beers, 2 SPT ‐negative beers, and barley, wheat, and maize extracts using both patient's serum and a maize LTP ‐specific in‐house developed polyclonal antibody from rabbit. Further, the immune reactive LTP of one beer was separated by HPLC and the chromatogram was compared to that of purified maize LTP . Results Beer SPT scored positive in 30/36 cases. The immunoblot analysis showed IgE reactivity at about 10 kD a against the two SPT ‐positive beers and against maize with both patient's serum and the polyclonal anti‐ LTP rabbit serum, whereas the two SPT‐negative beers, and barley extract scored negative. The immunodetected protein co‐migrated with maize LTP . Conclusion In beer‐allergic patients the diagnostic workup may point to the detection of some tolerated products that can be consumed risk‐free.
RETRACTED: Impairment of Central Leptin-Mediated PI3K Signaling Manifested as Hepatic Steatosis Independent of Hyperphagia and Obesity
Authors: James P. Warne, Farzad Alemi, Alison S. Reed, Jillian M. Varonin, Helen Chan, Merisa L. Piper, Mark E. Mullin, Martin G. Myers, Carlos U. Corvera, Allison W. Xu
Journal: Cell Metabolism (2011)
Dysfibrinogenemia in a Patient with Primary Hepatoma
Authors: Arthur von Felten, P. Werner Straub, Paul G. Frick
Journal: New England Journal of Medicine (1969)

In a female patient with hepatoma and a prolonged thrombin time, the coagulation defect was shown to be localized in the phase of fibrin monomer aggregation. The defect fulfilled all the preliminary laboratory criteria of the congenital dysfibrinogenemias. Exogenous inhibitors and fibrinolysis were excluded. Since no evidence for inheritance of the abnormality was found, it is suggested that the defect was acquired and that an abnormal fibrin monomer fraction was interfering with the aggregation of normal fibrin monomers. The abnormal fibrinogen is most probably synthesized by the hepatoma.
How Many Doctors?
Authors: John Lister
Journal: New England Journal of Medicine (1977)

The estimation of the number of doctors required to meet the medical needs of a country is a notoriously difficult and apparently unreliable exercise. Thus, in this country a committee1 was set up in 1955 under the chairmanship of Sir Henry Willink "to estimate on a long term basis and with due regard to all relevant considerations, the number of medical practitioners likely to be engaged in all branches of the profession in the future and the consequential intake of medical students required." These terms of reference related to the requirements of England, Scotland and Wales, and the committee took . . .
Effects of capsaicin, bradykinin and prostaglandin E2 in the human skin
Authors: JOANNA WALLENGREN, R. HAKANSON
Journal: British Journal of Dermatology (1992)

The actions and interactions of putative mediators of inflammation, such as substance P (SP), histamine, bradykinin and prostaglandins (PGE2) were studied in human skin. In addition, the effects of capsaicin were examined as it is known to release (and to deplete) SP and calcitonin gene‐related peptide from C‐fibres. The flare evoked by bradykinin was abolished by pretreatment with lignocain (local anaesthetic), compound 48/80 (mast‐cell histamine liberator), mepyramine (H1‐receptor antagonist) and indomethacin (cyclo‐oxygenase inhibitor) but was unaffected by atropine and ketanserin (serotonin antagonist). The weal response was not reduced by any of the drugs. The flare evoked by capsaicin was abolished by lignocaine and indomethacin but was unaffected by compound 48/80, mepyramine, atropine and ketanserin. The weal response was reduced by indomethacin. The flare response to bradykinin seems to reflect the activation of C‐fibres and associated mast cells, while the flare response to capsaicin seems to reflect the activation of C‐fibres only. Repeated injections of capsaicin and bradykinin produced tachyphylaxis (and cross‐tachyphylaxis) and greatly reduced the SP‐evoked flare. Capsaicin produced tachyphylaxis also after treatment of the skin with a local anaesthetic, suggesting that it develops independently of C‐fibre impulse flow. The tachyphylaxis produced by bradykinin and capsaicin seems to reflect the depletion of messenger peptides from the C‐fibres. The flare response to SP following capsaicin‐ or bradykinin‐induced desensitization gradually returned to normal after 5–8 weeks. The erythema evoked by PGE2 was reduced by 30% following pretreatment with lignocaine, mepyramine or compound 48/80. The dermal effects of prostaglandins seem to be partly indirect, involving C‐fibres and mast cells, and partly direct on the vascular bed. The importance of prostaglandins for C‐fibre‐mediated effects is reflected in the fact that indomethacin and acetylsalicylic acid were found to suppress axon‐reflex‐mediated responses.
From an Upstairs Window, Winter
Authors: Thomas B. Cole
Journal: JAMA (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Functional Implications of a Newly Characterized Pathway of 11,12-Epoxyeicosatrienoic Acid Metabolism in Arterial Smooth Muscle
Authors: Xiang Fang, Terry L. Kaduce, Neal L. Weintraub, Mike VanRollins, Arthur A. Spector
Journal: Circulation Research (1996)

Epoxyeicosatrienoic acids (EETs) are potent vasodilators derived from cytochrome P-450 metabolism of arachidonic acid. The rapid conversion of EETs to their corresponding dihydroxyeicosatrienoic acids (DHETs) has been proposed as a process whereby EETs are rendered biologically inactive. However, the vascular metabolism of EETs and the vasoactivities of EET metabolites have not been extensively studied. Accordingly, 11,12-EET metabolism was characterized in porcine aortic smooth muscle cells. The cells converted [ 3 H]11,12-EET to 11,12-DHET and to a newly identified metabolite, 7,8-dihydroxy-hexadecadienoic acid (DHHD). 11,12-DHET accumulation in the medium reached a maximum in 2 to 4 hours and then declined, whereas 7,8-DHHD accumulation increased continuously and exceeded the amount of 11,12-DHET by 8 hours. [ 3 H]11,12-EET conversion to radiolabeled 7,8-DHHD was reduced in the presence of unlabeled 11,12-DHET, indicating that 11,12-DHET is an intermediate in the conversion of 11,12-EET to 7,8-DHHD. This is consistent with a pathway whereby 11,12-EET is converted by an epoxide hydrolase to 11,12-DHET, which then undergoes two β-oxidations to form 7,8-DHHD. In porcine coronary artery rings contracted with a thromboxane mimetic, 11,12-DHET produced relaxation similar in magnitude to that produced by 11,12-EET (77% versus 64% relaxation at 5 μmol/L, respectively). 7,8-DHHD also produced vasorelaxation. Thus, the vasoactivity of 11,12-EET is not eliminated by conversion to 11,12-DHET and 7,8-DHHD. These results suggest that 11,12-DHET and its metabolite, 7,8-DHHD, may contribute to the regulation of vascular tone in the porcine coronary artery and possibly other vascular tissues.
Hemodynamic effects of intravenous sodium nitroprusside in the conscious dog.
Authors: M Pagani, S F Vatner, E Braunwald
Journal: Circulation (1978)

The hemodynamic effects of 7 min i.v. sodium nitroprusside (NP) were studied in conscious dogs previously instrumented for measurement of arterial pressure, cardiac output, regional blood flow distribution, left ventricular (LV) pressure, and internal dimensions. Nitroprusside, 25 microgram/kg/min, reduced mean arterial pressure by 23 +/- 3%. Cardiac output increased initially by 39 +/- 7% and returned toward control by the end of the infusion. Regional blood flows increased initially; the relative rise was greatest in the coronary (+ 225 +/- 39%), intermediate in the mesenteric (+ 98 +/- 23%) and iliac (+ 38 +/- 6%), and least in the renal (+ 10 +/- 3%) bed. By the end of the infusion period the vasodilation was unchanged in the iliac bed, less intense in the coronary and mesenteric, while in the iliac bed, blood flow was reduced and resistance was actually increased by 33 +/- 11% above control. A generalized vasonconstriction ensued after cessation of infusion. In contrast, when the drug was administered intra-arterially to the iliac bed, arterial pressure did not fall and only iliac vasodilation was observed. Peak cardiac effects were characterized by increases in heart rate and LV dP/dt, along with marked reduction in LV end-systolic diameter (- 13 +/- 2%), and in end-diastolic diameter (-17 +/- 2%) and pressure. LV end-diastolic diameter fell even heart rate was maintained at a constant rate by pacing. Thus, in the conscious dog, NP reduced LV dimensions substantially, while inducing changes in peripheral beds. The differences in these effects depend on interactions between the direct effects of NP and the opposing effects of reflex adjustments which appear sufficiently powerful to result in net constriction of the iliac bed late during the infusion.
In vitro Effect of oxLDL and PHA on Lymphocyte Proliferation/Cytotoxicity and Interleukin-2 Production in Patients with Atherosclerosis
Authors: M. Mahmoudi, F. Siassi, M.J. Mahmoudi, F. Shokri, M. Eshraghian, A. Zarnani, N. Rezaei, A. Saboor-Yaraghi
Journal: Journal of Allergy and Clinical Immunology (2011)
Nondisjunction — A View from Ringside
Authors: Neil E. Lamb, Terry J. Hassold
Journal: New England Journal of Medicine (2004)

Chromosome nondisjunction lands a heavy blow on the chin of humanity. The improper segregation of chromosomes during meiosis leads to chromosomally unbalanced eggs or sperm. If these gametes participate in fertilization, the outcome is an aneuploid embryo, with either trisomy (one chromosome too many) or monosomy (one chromosome too few). Since most such embryos are inviable, one might expect that these errors would be extremely rare. This is true for most organisms, but our own species is a notable exception: aneuploidy is identified in at least 5 percent of all clinically recognized pregnancies, making it the leading known cause of . . .
Design of an epidemiologic study of drinking water arsenic exposure and skin and bladder cancer risk in a U.S. population.
Authors: M R Karagas, T D Tosteson, J Blum, J S Morris, J A Baron, B Klaue
Journal: Environmental Health Perspectives (1998)

Ingestion of arsenic-contaminated drinking water is associated with an increased risk of several cancers, including skin and bladder malignancies; but it is not yet clear whether such adverse effects are present at levels to which the U.S. population is exposed. In New Hampshire, detectable levels of arsenic have been reported in drinking water supplies throughout the state. Therefore, we have begun a population-based epidemiologic case-control study in which residents of New Hampshire diagnosed with primary squamous cell (n = 900) and basal cell (n = 1200) skin cancers are being selected from a special statewide skin cancer incidence survey; patients diagnosed with primary bladder cancers (n = 450) are being identified through the New Hampshire State Cancer Registry. Exposure histories of these patients will be compared to a control group of individuals randomly selected from population lists (n = 1200). Along with a detailed personal interview, arsenic and other trace elements are being measured in toenail clipping samples using instrumental neutron activation analysis. Household water samples are being tested on selected participants using a hydride generation technique with high-resolution inductively coupled plasma mass spectrometry. In the first 793 households tested arsenic concentrations ranged from undetectable (0.01 microgram/l) to 180 microgram/l. Over 10% of the private wells contained levels above 10 microgram/l and 2.5% were above 50 microgram/l. Based on our projected sample size, we expect at least 80% power to detect a 2-fold risk of basal cell or squamous cell skin cancer or bladder cancer among individuals with the highest 5% toenail concentrations of arsenic.
Role of nitric oxide in reactive hyperemia of the guinea pig heart.
Authors: M M Kostic, J Schrader
Journal: Circulation Research (1992)

To evaluate the role of nitric oxide (NO) in the flow response after brief coronary arterial occlusion, NO formation by the isolated guinea pig heart was assessed by a specific difference spectrophotometric assay. Release of NO under basal conditions was 121.8 +/- 10.5 pmol x min-1 and increased to 211.1 +/- 16.8 pmol x min-1 after 60 seconds of coronary occlusion. Simultaneously, release of cGMP and adenosine increased by 87% and 652%, respectively. The kinetics of NO release paralleled the reactive hyperemic flow response. Inhibition of NO synthesis with nitro-L-arginine methyl ester (L-NAME, 30 microM) significantly reduced basal flow and attenuated reactive hyperemia, flow repayment, and repayment ratio. L-NAME decreased release of cGMP but significantly increased adenosine release under basal conditions and during reactive hyperemia. Oxyhemoglobin (5 microM) potentiated the effects of L-NAME. The stereoisomer nitro-D-arginine methyl ester was ineffective. Our results suggest 1) NO is an important regulator of coronary flow during reactive hyperemia as well as under basal flow conditions and 2) the significance of the increased adenosine release when NO synthesis is inhibited remains to be determined.
THE PRESENT ATTITUDE OF SANITARIANS AND BOARDS OF HEALTH IN REGARD TO PULMONARY TUBERCULOSIS.
Authors: BENJAMIN LEE
Journal: JAMA (1897)

The question of the communicability of pulmonary tuberculosis, consumption of the lungs or pulmonary phthisis, has long passed the boundary of discussion with the great mass of the medical profession. Here and there an individual who places a very high estimate on his reputation for consistency persists in attempting to controvert it, because it was not the belief in which he was educated, and because he opposed it when, in consequence of the researches of the bacteriologic investigators, it was first resuscitated. But, in the main, the consensus of professional opinion strongly supports it. Those who take an intelligent interest in the promotion of public health and have thus been led to give the subject more especial attention are even more thoroughly convinced of the fact than are those who confine their studies strictly to therapeutics and the daily routine of practice; while those whose official positions make it their
The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission
Authors: Xiao-Jun Huang, Hong-Hu Zhu, Ying-Jun Chang, Lan-Ping Xu, Dai-Hong Liu, Xiao-Hui Zhang, Bin Jiang, Qian Jiang, Hao Jiang, Yu-Hong Chen, Huan Chen, Wei Han, Kai-Yan Liu, Yu Wang
Journal: Blood (2012)
134 CHEMOKINE RECEPTOR AND ATP-BINDING CASSETTE TRANSPORTER GENE POLYMORPHISMS AS RISK FACTORS FOR ANASTOMOTIC AND NON-ANASTOMOTIC STRICTURES DEVELOPMENT FOLLOWING LIVER TRANSPLANTATION
Authors: S. Iacob, V.R. Cicinnati, A. Dechene, C.G. Klein, I. Popescu, A. Paul, G. Gerken, S. Beckebaum
Journal: Journal of Hepatology (2010)
Operant Conditioning of Rectosphincteric Responses in the Treatment of Fecal Incontinence
Authors: Bernard T. Engel, Parviz Nikoomanesh, Marvin M. Schuster
Journal: New England Journal of Medicine (1974)

Six patients with severe fecal incontinence and manometric evidence of external-sphincter impairment were taught to produce external-sphincter contraction in synchrony with internal-sphincter relaxation. These responses were induced by rectal distention. During follow-up periods ranging from six months to five years, four of the patients remained completely continent, and the other two were definitely improved. One patient who was trained to relax her internal sphincter as well as to contract her external sphincter not only was continent but also regularly had normal bowel movements, which she had not had before. The training technic was relatively simple to apply, and learning occurred within four sessions or less. The findings highlight the Importance of synchronized rectosphincteric responses in the maintenance of fecal continence, and they show that these responses can be brought under voluntary control in patients with chronic fecal Incontinence, even when the incontinence is secondary to organic lesions. (N Engl J Med 290:646–649, 1974)
The Heart: Old and New Views.
Authors: Horance Lance Flint
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Endoscopic mucosal resection of colonic polyps: a large prospective single centre series
Authors: G. Longcroft-Wheaton, R. Mead, M. Duku, P. Bhandari
Journal: Gut (2011)

<h3>Introduction</h3> The traditional approach to the management of large colonic polyps has been surgery. Endoscopic mucosal resection (EMR) is an emerging technique for the removal of large colorectal lesions. Most of the published literature comes from Japan, with limited data regarding safety, efficacy and outcome in the west. We aim to assess the feasibility and safety of EMR in the colon in a western setting. <h3>Methods</h3> A prospective review of patients undergoing EMR of colonic neoplasia &gt;2 cm in size was performed. All patients were tertiary referrals from experienced consultants. The polyps were considered technically challenging due to size, difficult lesion access (peri-diverticular, peri-appendicular, touching the dentate line), or recurrences on previous EMR scars. They were referred to our service prior to surgical referral. Lesions were assessed using indigocarmine chromoendoscopy, and lesions with features suggestive of invasive malignancy were excluded. Completeness of resection was recorded by the endoscopist. Patients were followed up endoscopically where appropriate to assess for incomplete resection or recurrence. <h3>Results</h3> 214 patients with 214 polyps underwent EMR. The mean size was 43 mm (range 20–150). 180 were flat and 46 were on the right side of the colon. Primary reason for referral was the size in 91 cases, lesion access in 107 cases and a previous failed resection in 16 cases. Endoscopic clearance at first attempt was achieved in 92% of cases. Residual or recurrent disease was seen at the first endoscopic follow-up in 17% cases requiring further endoscopic resection. Overall endoscopic cure has been achieved in 95% of patients. Three patients went to surgery due to failed endoscopic resection. There were procedure related complications in 15/214 (7%) of cases. This consisted of delayed bleeding in nine patients, immediate bleeding in two cases and four post polypectomy syndrome. The risk of complications was independent of size or location. There were 13 cancers (7 &gt; sm1 invasion) in flat polyps and 4 pedunculated polyp cancers (1 &gt; Haggitt 2). 13 of these cases underwent surgery. Taking the cost of surgery as £12,000 and the cost of EMR as £561 this represents a potential cost saving of £2,231,946 for the cohort. <h3>Conclusion</h3> This is the largest UK series demonstrating that EMR is a safe and effective treatment for large difficult polyps with an overall complication rate of 7%. It avoided surgery in 93% of cases with substantial cost savings. We believe that EMR of large and difficult benign polyps should be the new standard of care.