tbuckley/cabot-search huggingface dataset:
Otorrhoea
Authors: M. Pankhania, O. Judd, A. Ward
Journal: BMJ (2011)

5-HT<sub>2A</sub> serotonin receptors are unusual among G-protein coupled receptors in that they can be internalized and desensitized, in some cell types, in an arrestin-independent manner. The molecular basis of the arrestin-insensitivity of 5-HT<sub>2A</sub> receptors is unknown but is probably caused, in part, by the apparent lack of agonist-induced 5-HT<sub>2A</sub> receptor phosphorylation. Because the arrestin-insensitivity of 5-HT<sub>2A</sub> receptors is cell-type selective, we used a “constitutively active” arrestin mutant that can interact with agonist-activated but nonphosphorylated receptors. We show here that this “constitutively active” arrestin mutant (Arr2-R169E) can force 5-HT<sub>2A</sub> receptors to be regulated by arrestins. Cotransfection of 5-HT<sub>2A</sub> receptors with Arr2-R169E induced agonist-independent 5-HT<sub>2A</sub> receptor internalization, and a constitutive translocation of the Arr2-R169E mutant to the plasma membrane, whereas wild-type Arrestin-2 had no effect. Additionally, Arr2-R169E, unlike wild-type arrestin-2, induced a significant decrease in efficacy of agonist-induced phosphoinositide hydrolysis with an unexpected increase in agonist potency. Radioligand binding assays demonstrated that the fraction of receptors in the high-affinity agonist binding-state increased with expression of Arr2-R169E, indicating that Arr2-R169E stabilizes the agonist-high affinity state of the 5-HT<sub>2A</sub> receptor (R*). Intriguingly, the agonist-independent interaction of Arr2-R169E with 5-HT<sub>2A</sub> receptors was inhibited by inverse agonist treatment and is thus probably caused by the high level of 5-HT<sub>2A</sub>receptor constitutive activity. This is the first demonstration that a constitutively active arrestin mutant can both induce agonist-independent internalization and stabilize the agonist-high affinity state of an arrestin-insensitive G protein coupled receptor.
The role of liver stiffness by ARFI elastography in the diagnosis of porto-sinusoidal vascular disease: comparison with patients with chronic portal vein thrombosis
Authors: Stefania Gioia, Silvia Nardelli, Francesca Aprile, Barbara Lattanzi, Lorenzo Ridola, Adriano De Santis, Manuela Merli, Oliviero Riggio
Journal: Journal of Hepatology (2020)
Natural history of unexplained biliary dilation
Authors: N. M. Kelly, B. Tharian, T. C. K. Tham
Journal: Gut (2011)

<h3>Introduction</h3> With the increasing use and availability of MRCP imaging incidental duct dilation is common. There are no guidelines as to how these patients should be investigated or followed. We sought to retrospectively identify a cohort of patients with biliary dilation on MRCP and assess the incidence of sinister pathology. <h3>Methods</h3> Local MRCP database was searched to identify patients with biliary dilation. Data was collected on patient demographics, radiological diagnosis, diameter of common bile duct and what follow-up was carried out. Patients with unexplained biliary dilation were followed via search of radiological database and clinical record database. <h3>Results</h3> 1386 MRCP results were reviewed from May 2005 to July 2009. 348 (25.1%) were identified in which a dilated bile duct was reported but no obstructing lesion was seen. 17 (4.9%) patients were excluded because they were referred from an outside institution for MRCP and follow-up data was unavailable, leaving 331 for review. Of these, presumed diagnoses for biliary dilatation included gallstones (n = 146, 44.1%), post-cholecystectomy (n = 86, 26%), pancreatitis (n = 27, 8.1%), cholecystitis (n = 17, 5.1%), duodenal diverticulum (n = 4, 1.2%), choledochocele (n = 1, 0.3%), gallbladder surgery unspecified (n = 1, 0.3%) and strawberry gallbladder (n = 1, 0.3%). There were 48 (14.5%) cases of unexplained biliary dilation, which constituted the follow-up group. Females predominated (n = 31, 64.6%). Mean age was 65 years (range 34–96). Duct diameter ranged from 7–22 mm (mean 11 mm). Follow-up was available on 44 patients (91.6%). Mean follow-up was 35 months (range 6–64 months). 8 (18.2%) patients had ERCP. All were normal except 1 (12.5%), demonstrating choledocholithiasis. 9 (20.5%) patients had duodenoscopy, all of which were normal. One patient (2.3%) had an endoscopic ultrasound, which was normal. Mortality in the follow-up group was 13.6% (n = 6; 1 myocardial infarction, 1 respiratory failure, 1 uterine carcinoma, 1 intracranial haemorrhage, 1 unknown, 1 pancreatic carcinoma). Two (4.5%) patients were diagnosed with carcinoma head of pancreas 14 months and 8 months, respectively, after their index MRCP. One was an 87-year-old female who had an ERCP, which confirmed duct dilation but no obstructive cause. A third CT scan 14 months later confirmed probable metastatic carcinoma from head of pancreas. The other was a 34-year-old man diagnosed with carcinoma head of pancreas 8 months later after presenting with obstructive jaundice followed by an ERCP and stent. He died 21 months after his index MRCP. <h3>Conclusion</h3> In this retrospective study of incidental unexplained biliary dilatation, a small but significant 4.5% of patients were diagnosed with a malignant aetiology. We recommend that all patients with incidental unexplained duct dilation on MRCP are closely followed up and considered for endoscopic ultrasound.
PWE-098 Earlier Use Of Azathioprine In Ulcerative Colitis Does Not Alter Subsequent Need For Hospitalisation, Biologic Therapy, Or Colectomy
Authors: R Sood, S Ansari, T Clark, PJ Hamlin, AC Ford
Journal: Gut (2014)

<h3>Introduction</h3> Azathioprine (AZA) is an established treatment for ulcerative colitis (UC). However, controversy exists regarding its efficacy in inducing and maintaining clinical remission, particularly with the advent of biologics which, unlike AZA, have been tested in large, rigorously designed randomised controlled trials. We studied the effectiveness of AZA as second-line therapy after failure of 5-aminosalicylates (5-ASAs) in a large cohort of UC patients, with particular emphasis on whether its earlier use alters the natural history of the disease course. <h3>Methods</h3> All UC patients treated with AZA at our centre were identified from a prospective electronic database. We excluded individuals who had received either infliximab or ciclosporin as a bridge to AZA. The following demographic data were collected: gender, age at diagnosis, age at AZA commencement, concomitant therapy at AZA commencement, and duration of disease prior to AZA commencement. We assessed response to therapy at 4 months and remission at last point of follow-up, using physicians’ global assessment, need for hospitalisation, escalation of therapy to a biologic, or colectomy, and serious adverse events (including infections and malignancies). We examined whether earlier AZA use (within 12 months of diagnosis) reduced need for hospitalisation, biologic therapy, or colectomy. <h3>Results</h3> In total, 255 patients were included (55% male, mean age at diagnosis 36.4 years). Mean age at commencing AZA was 42.3 years. Mean disease duration prior to AZA commencement was 70 months. Concomitant therapy at AZA commencement was oral 5-ASAs in 87%, topical 5-ASAs in 22%, and oral prednisolone in 77%. At 4 months, 207 (81%) of 255 patients were still on AZA (46 had discontinued due to adverse events and 2 due to non-response), and 163 (64%) had responded to therapy. There were 165 (65%) patients still receiving AZA at last point of follow-up, of whom 153 (60%) were in remission (mean duration of therapy 64.5 months). 26 patients required admission to hospital for an exacerbation during AZA treatment, 20 patients ultimately required biologic therapy, and 21 underwent colectomy. Among 90 patients receiving AZA within 12 months of diagnosis, 21 (23%) patients experienced one of these three endpoints, compared with 29 (19%) of 154 who commenced AZA &gt;12 months after diagnosis (p = 0.40). Serious adverse events included 6 cases of pancreatitis, 6 cases of cancer (3 non-melanoma skin cancers) and 1 case of neutropenic sepsis presenting within 1 month of AZA commencement. <h3>Conclusion</h3> AZA is a safe and effective therapy for UC patients who fail 5-ASAs, and should continue to be used prior to instituting biologic therapies. However, earlier use does not seem to alter the natural history of the disease. <h3>Disclosure of Interest</h3> None Declared.
Beiträge zur Kenntnis der septischen Pleuraempyeme unter besonderer Berücksichtigung der Spätresultate
Journal: JAMA (1934)

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
Expression of concern
Journal: BMJ (2005)

that more sources will reduce the variability between sources is small.We based our comparison on 100 drugs that are consumed most often in our hospital.We have little reason to assume that the choice was biased and included problematic drugs.We tackled only adjustments for renal impairment, but we can guess that the adjustment for liver failure, for example, is no better described or referenced. ConclusionsLooking for evidence on the efficiency of interventions, clinicians are taught to expect secondary sources (for example, systematic reviews in the Cochrane Library) to use their primary sources in a methodical manner: transparent and reproducible workflow, a thorough and explicit search for references, elimination of bias, and a short description of the primary sources.What should clinicians (and their patients) expect from a reliable secondary source of drug information?The methods used to retrieve information and data on use should be described and made available to the reader-for example, which kind of data are solicited from the manufacturer, how their reliability is judged, and how the data are translated into quantitative recommendations.Readers should be told if other sources of primary information are searched, which methods are used to search them, and again how the information is translated into recommendations.Primary data should be summarised, and the reader should have easy access to it.If possible, quantitative recommendations on dosages and dosing intervals should be made.If not, the reason for the qualitative recommendation should be made clear.The basics of drug prescription-dosage and dosing interval, contraindications, and expected adverse effects-should be no less evidence based than the efficacy and effectiveness of a drug or intervention.
Noninvasive Ventilation
Authors: Robert E. Hillberg, Douglas C. Johnson
Journal: New England Journal of Medicine (1997)

When ventilatory support is delivered without establishing an endotracheal airway, it is termed noninvasive ventilation. Traditionally, noninvasive ventilation has been given with the use of devices that apply intermittent negative extrathoracic pressure. The advent of positive-pressure ventilation that is delivered through a nasal or face mask has greatly expanded the use of noninvasive ventilation. Such ventilation has a role in the management of acute and chronic respiratory failure in many patients and may have a role for some patients with heart failure. Noninvasive approaches can preserve normal swallowing, feeding, and speech. Cough and physiologic air warming and humidification are also . . .
The English Pioneers of Anǽsthesia (Beddoes, Davy, and Hickman).
Journal: JAMA (1952)

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
The nationwide cancer genome screening project in Japan, SCRUM-Japan GI-SCREEN: Efficient identification of cancer genome alterations in advanced colorectal cancer
Authors: S. Yuki, T. Kato, H. Taniguchi, T. Hamaguchi, K. Akagi, T. Denda, T. Mizukami, E. Oki, T. Yamada, M. Shiozawa, T. Kudo, T. Tamura, T. Esaki, D. Naruge, T. Kajiwara, S. Nomura, S. Fujii, K. Shitara, A. Ohtsu, T. Yoshino
Journal: Annals of Oncology (2017)
Correspondence Pain relief with Emla of ulcerating lesions in mycosis fungoides Exanthematous lichen planus in a child-response to acitretin Serratia marcescens granuloma Darier's disease presenting as isolated hyperkeratosis of the breasts Contact dermatitis to nasturtium Geographical differences in prevalence of hepatitis C virus infection in PCT (porphyria cutanea tarda) Lack of the R59W South African founder effect mutation in protoporphyrinogen oxidase in a British patient with homozygous …
Journal: British Journal of Dermatology (1997)
Pneumocystis carinii pneumonitis occurring in an adopted Korean infant
Authors: B. H. Hyun
Journal: JAMA (1966)

GENERALLY THOUGHT to be a protozoan,<i>Pneumocystis carinii</i>has been known for many decades to be the cause of a specific infection of the lung,<i>P carinii</i>pneumonitis. In Europe,<i>P carinii</i>pneumonitis is known to occur predominantly in debilitated and premature infants six weeks to a few months of age, and has been encountered primarily in epidemics in nurseries, resulting in many deaths.<sup>1,2</sup>Deamer and Zollinger<sup>3</sup>brought this condition to the attention of North American physicians in 1953. In 1956, Gagne and Hould<sup>4</sup>presented the first three cases from Canada and since then, an increasingly large number of cases have been recognized in the North American continent. The condition had not been reported in the Far East until 1959, when Lim<sup>5</sup>recorded an epidemic of 30 cases in infants occurring in a Korean orphanage. In 1960, Lim and Moon<sup>6</sup>presented epidemiologic and clinical studies
Abdominal Epilepsy
Authors: Matthew T. Moore
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Babb and Eckman (222:65, 1972) in their article, "Abdominal Epilepsy," have justifiably revived interest in this syndrome, which may be unrecognized because of lack of familiarity with it by many physicians. However, their statement that the condition is a "rare entity" is not entirely true, nor does it occur "uniquely in children or young adolescents." It may and does occur in adults, as is amply documented in the medical literature. This brings me to my main thesis. Apparently, the authors have failed to review the literature prior to 1951, since their earliest reference is that of Livingston, "Abdominal Pain as a Manifestation of Epilepsy (Abdominal Epilepsy) in Children" (<i>J Pediatr</i>38:687,1951). On the first page of his article, Livingston states, "although abdominal pain has been known to be associated with epilepsy as far back as Hughlings Jackson, the syndrome of 'abdominal epilepsy' seems to have been first
THE PROSTATE.
Authors: JOHN B. MURPHY
Journal: JAMA (1902)

In the very recent literature the surgery of the prostate has been given a much deserved prominence. The patient and long suffering of those with prostatic trouble is unnecessary to mention as an incentive to active investigation in this particular field. We believe that the recent procedures have been sufficiently tried to justify their regular performance, and that they give us reasonable assurance of safety to the patient and permanency of relief. It appears to us that it is now a matter of improvement of technic in the operations and a dissemination among the general profession of the importance of the early performance of operative procedures that is most needed. Before citing cases the author takes the liberty of considering the anatomy and physiology of the prostate, as well as the etiology and pathology of prostatic hypertrophy. <h3>ANATOMY.</h3> The prostate is a glandular and muscular body situated in front of
THE CURRENT INDEX.
Journal: JAMA (1902)

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
Clinical Summaries
Journal: Circulation (2009)

Previous studies have suggested that low total cholesterol levels are associated with an increased risk of intraparenchymal hemorrhage.The present study extends the evidence of an association between low total cholesterol levels and hemorrhage risk.We showed an association between low low-density lipoprotein cholesterol (Ͻ80 mg/dL [Ͻ2.06 mmol/L]) and increased risk of death due to intraparenchymal hemorrhage in the general population.The basic pathology of intraparenchymal hemorrhage is arteriolosclerosis, characterized by angionecrosis (destruction) of smooth muscle cells in intracerebral small arteries, as opposed to atherosclerosis (plaque formation) in medium to large arteries.Low-density lipoprotein cholesterol may have an opposite effect on development of intraparenchymal hemorrhage than on coronary heart disease.The present finding suggests that low low-density lipoprotein cholesterol may be an independent risk factor for intraparenchymal hemorrhage.See p 2136.
Effects of glucocorticoids and mineralocorticoids on proliferation and maturation of human peripheral blood stem cells
Authors: Stéphanie Grafte‐Faure, Catherine Leveque, Marc Vasse, Claudine Soria, Vic Norris, Jean‐Pierre Vannier
Journal: American Journal of Hematology (1999)

It has been shown that hematopoietic progenitors can be expanded ex vivo in the presence of various cytokine combinations. Glucocorticoids (GC) are involved in the self-renewal of erythroid progenitors in chicken. To see whether GC have a similar effect on hematopoiesis in humans, CD34+ peripheral blood stem cells were cultured in serum free medium in the presence of a GC, triamcinolone acetonide. However, our results demonstrate an inhibition of both erythroid and granulocyte-macrophage (GM) proliferation and a modification of erythroid colony morphology. Furthermore, RU38486 (Mifepristone), a potent GC antagonist, was unable to reverse the inhibitory effect of triamcinolone acetonide. We also identified and characterized another steroid subfamily, the mineralocorticoid (MC) subfamily, in human PB CD34+ cells. The MC, aldosterone, significantly enhanced GM colony formation and diminished the erythroid colony number. Neither of effects were inhibited by ZK91587, an antagonist specific to the MC receptor (MCR). In contrast, ZK91587 reversed the stimulatory effect of deoxycorticosterone on GM colony formation. Cytoplasmic staining for MCR was observed in CD34+ cells incubated with a polyclonal antiserum raised against human MCR. To our knowledge, this is the first demonstration of the presence of MCR in human PB CD34+ cells. Am. J. Hematol. 62:65–73, 1999. © 1999 Wiley-Liss, Inc.
A phase 1 study of a novel inhibitor of protein phosphatase 2A alone and with docetaxel.
Authors: Vincent M. Chung, Aaron Scott Mansfield, John Kovach
Journal: Journal of Clinical Oncology (2014)

TPS2636 Background: Protein phosphatase 2A (PP2A) is a target of several viral oncoproteins suggesting that it contributes to tumor suppression. Several human cancers have decreased PP2A function by mutations or by increased cellular PP2A inhibitors, CIP2A and SET, including about 40% of NSCLC and 60% of prostate cancers. Tumors with decreased PP2A activity may be particularly vulnerable to further PP2A inhibition. Recently, several groups have shown that inhibition of PP2A activity with a novel small molecule, LB-100, enhances the effectiveness of anticancer agents (temozolomide, docetaxel, doxorubicin, cisplatin) and radiation against different human cancer cell types in vivo without significantly enhancing toxicity. LB-100 inhibition of PP2A appears to potentiate cytotoxic therapy by altering regulation of cell cycle with enhanced S-phase entry and delayed mitotic exit and inhibition of DNA-damage-response including suppression of p53 induction and homologous recombination repair (HRR). Impaired HRR in PP2A deficient cells increases their sensitivity to PARP inhibition (PARPi), leading to the suggestion that PP2A status may indicate cancer cell vulnerability to PARPi. Based on these data, we sought to determine the maximum tolerated dose of LB-100 as a single agent, and in combination with docetaxel. Methods: The aims of this two-part phase I study are to determine the MTD of LB-100 alone given intravenously over 15 minutes daily for 3 days every 3 weeks, and the MTD when given with docetaxel on day 2. In part 2, the dose of LB-100 will start two levels lower than its MTD as a single agent with docetaxel given at 60mg/m2. LB-100 will then be escalated to its MTD, if tolerated, and docetaxel will be escalated to 75mg/m2. Eligible patients are >=18 y with progressive or metastatic tumors who have failed available standard treatment. In part 2, docetaxel naïve patients will be entered who have failed standard treatment. All patients must have an ECOG performance status of 0 or 1, have recovered from acute adverse effects of prior therapies, and have adequate bone marrow, renal, and hepatic function. Clinical trial information: NCTO1837667.