tbuckley/cabot-search huggingface dataset:
Connexin 32 gap junctions enhance stimulation of glucose output by glucagon and noradrenaline in mouse liver
Authors: Frank Stümpel, Thomas Ott, Klaus Willecke, Kurt Jungermann
Journal: Hepatology (1998)

Gap junctions connect neighboring cells via intercellular channels composed of connexins (Cx). Connexin 32 (Cx32) is the main connexin in hepatocytes. Gap junctions propagate a signal from periportal to perivenous hepatocytes generated by electrical stimulation of sympathetic liver nerves. Therefore, it was the aim of this study to examine the involvement of hepatocellular gap junctions in hormonal regulation. In perfused livers from wild-type mice and Cx32-deficient mice, the stimulation of glucose release by varying noradrenaline and glucagon concentrations was investigated. At saturating hormone concentrations, glucose release was the same in wild-type and Cx32-deficient livers. However, glucose output was significantly smaller in Cx32-deficient than wild-type livers at half-maximally effective hormone concentrations. Because the two hormones circulate at less than half-saturating concentrations and because they are degraded during passage of blood through the liver, they lose efficiency from the periportal to the perivenous zone. In wild-type livers, this decrease in efficiency can be partially compensated by intercellular signal propagation through gap junctions, resulting in higher hormone actions than in Cx32-deficient livers. It is concluded that gap junctions are not only involved in intercellular propagation of nervous, but also of hormonal signals from periportal to perivenous hepatocytes.
Iatrogenic intramural dissection of the gallbladder wall can mimic post-ERCP cholecystitis
Authors: M. Girotti, N. Gupta, B. Schirmer, M. Sarti, A. Choudhri, B. Arslan, A. Schroen
Journal: Endoscopy (2007)

A 28-year-old female was referred for surgical management of acute cholecystitis 1 day after endoscopic retrograde cholangiopancreatography (ERCP) and biliary sphincterotomy, because of the finding of a 15-mm-thick gallbladder wall on right upper quadrant ultrasonography ([Figure 1]). Pre-ERCP ultrasonography ([Figure 2]) and magnetic resonance cholangiopancreatography ([Figure 3]) demonstrated a 2.8-mm gallbladder wall and a patent cystic duct. The fluoroscopic images of the ERCP were reexamined and it was apparent that introduction of the guide wire had caused a dissection of the gallbladder wall which was visualized only after the injury had been exacerbated by injection of contrast intramurally ([Figure 4]). In the absence of fever, leukocytosis, a positive Murphy’s sign, or pericholecystic fluid on ultrasound images, the gallbladder wall thickening was concluded to represent an iatrogenic injury. We monitored the patient with serial abdominal exams to rule out a perforation and were able to discharge her with conservative management alone. Two months later she underwent an elective laparoscopic cholecystectomy for symptoms attributed to cholecystitis. A mural hematoma was seen upon initial visualization of the gallbladder ([Figure 5]) and confirmed by histopathology.
Reducing junior doctors' hours
Authors: C Raine, J B Irving
Journal: BMJ (1991)

A second criticism is that treatment with intra- nasal steroid aerosols was deliberately withheld from all subjects.It is now generally accepted that this form of treatment is so effective for seasonal allergic rhinitis that if it is allowed immunotherapy cannot produce a significant improvement in symptom scores.Nevertheless, for severe hay fever steroid aerosols are the standard treatment with which immunotherapy must be compared (together with its risks).To give suboptimal supportive treatment to patients treated with placebo might be acceptable in a trial of some exceedingly important new form of treatment, provided the position was made clear to the volunteers.In a trial of yet another formulation of conventional vaccine for hay fever the ethics seem dubious.The third point of criticism concerns the discussion of the reactions experienced by patients in the trial.Although 523 active injections were administered, there were only 21 actively treated patients.The necessary courses of injection that they received provoked an episode of anaphylaxis in one and generalised urticaria in another: a reaction rate of nearly 10%.The instances of fatal
Managing gastric cancer in Britain: a Japanese experience
Authors: T. Sano
Journal: BMJ (1997)

When the endoscopist drew the scope out of her patient's stomach without taking a picture I was speechless. She was talking to the patient, “Well done, Mr Smith. Your stomach is normal.” OK, I thought to myself, but who can prove it without pictures? I whispered to the endoscopist, “If he is found to have an advanced gastric cancer 12 months from now how can you prove that his stomach looked normal today?” This question was not meant to sound malicious. I was genuinely concerned that an early gastric cancer could have been overlooked.

Japanese surgeons have published countless papers on the early detection of gastric cancer, the high curability, the low morbidity and mortality, the high survival rates, and the benefits of radical lymphadenectomy. The data diverge so markedly from those of Western countries that many people (on both sides) can hardly believe that they are discussing the same disease.

Several British surgeons have visited the National Cancer Center Hospital in Tokyo to convince themselves that the Japanese data are not fabricated. During one professor's three week stay he …
Neratinib (HKI-272), an irreversible pan erbB receptor tyrosine kinase inhibitor: phase 2 results in patients with advanced HER2+ breast cancer.
Authors: HJ Burstein, Y Sun, AR Tan, L Dirix, JJ Vermette, C Powell, C Zacharchuk, RA Badwe
Journal: Cancer Research (2009)

Abstract Abstract #37 Background: Neratinib (HKI-272) irreversibly inhibits the tyrosine kinase receptors, erbB1 (EGFR) and erbB2 (HER2). In a phase 1 study, neratinib was tolerable and demonstrated antitumor activity in patients (pts) with solid tumors, including 8 of 25 evaluable pts with erbB2-positive advanced breast cancer. In this open-label, 2-arm phase 2 study, pts with stage IIIB, IIIC or IV erbB2-positive advanced breast cancer were evaluated to further characterize the safety and efficacy of neratinib.&amp;#x2028; Methods: ErbB2 gene amplification in tumor tissue, by FISH was a requirement for study entry. Pts were assigned to arm A if they had prior treatment with trastuzumab and to arm B if they had no prior treatment with trastuzumab or other erbB2-targeted drug. All pts received oral doses of 240 mg of neratinib daily. The primary endpoint was progression-free (PFS) survival rate at 16 weeks (wks).&amp;#x2028; Results: Enrollment of 136 pts (arm A: 66 pts; arm B: 70 pts; median age 50 years [range 31-83 years]) was completed in November 2007. Common neratinib-related adverse events (AEs), any grade, were diarrhea (89%), nausea (29%), vomiting (23%), fatigue (16%), and anorexia (15%). Diarrhea was the only ≥grade 3 AE that occurred in ≥5% of pts, 26/136 (19%) total pts, 27% in arm A and 11% in arm B. Dose reductions occurred in 27% total pts, 36% in arm A and 19% in arm B, most commonly because of diarrhea. The main reasons for discontinuation of the study were disease progression (arm A: 74%, arm B: 43%), and AEs (arm A: 8%, arm B: 4%).&amp;#x2028; 124 pts (arm A: 61 pts, arm B: 63 pts) were evaluable for efficacy based on independent assessment and 131 pts (arm A: 65 pts, arm B: 66 pts) were evaluable based on investigator assessment. The objective response rates (complete or partial response) were 26% (95% CI 16%, 39%) in arm A, 51% (95% CI: 38%, 64%) in arm B for independent assessment and 34% (95% CI: 23%, 47%) in arm A, 62% (95% CI: 49%, 74%) in arm B for investigator assessment. The 16-wk PFS rates were 61% in arm A, 75% in arm B (independent); 57% in arm A, and 78% in arm B (investigator). The median PFS for independent [and investigator assessment] was 23 [22] wks in arm A and 40 [35] wks in arm B.&amp;#x2028; Discussion: Neratinib demonstrates robust antitumor activity in pts with erbB2-positive advanced breast cancer, with objective response rates of 26% in pts who had prior treatment with trastuzumab and 51% in pts who had no prior treatment with trastuzumab. Additional updated efficacy and safety data will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 37.
TCT-841 Comparative Efficacy of Bleeding Avoidance Strategies by Preprocedural Risk for Access Site Hematoma in Patients Undergoing Peripheral Vascular Interventions
Authors: Daniel Ortiz, Anna Tyszkowska, Maharaj Singh, Arshad Jahangir, Suhail Allaqaband, Mark W. Mewissen
Journal: Journal of the American College of Cardiology (2014)
Reply from Authors re: Ryan P. Kopp, Stephen J. Freedland, J. Kellogg Parsons. Associations of Benign Prostatic Hyperplasia With Prostate Cancer: The Debate Continues. Eur Urol 2011;60:699–700
Authors: David D. Ørsted, Stig E. Bojesen, Sune F. Nielsen, Børge G. Nordestgaard
Journal: European Urology (2011)
OC-068 Algorithmic Management of Radiation-Induced Gi Symptoms is Highly Effective: the Orbit Randomised Controlled Trial
Authors: H J Andreyev, B Benton, A Lalji, K Pennert, J O Lindsay, H Gage, C Norton
Journal: Gut (2013)

<h3>Introduction</h3> Chronic gastrointestinal (GI) symptoms after pelvic radiotherapy are common. Most affected patients never see a GI specialist. We developed a comprehensive algorithm to direct management of new GI symptoms after pelvic radiotherapy. A 3 arm randomised controlled trial was performed to test 2 hypotheses: (1) Algorithm directed intervention is beneficial compared to no intervention (2) outcomes are not worse when patients are managed by a nurse rather than a gastroenterologist. <h3>Methods</h3> Patients treated with pelvic radiotherapy &gt; 6 months earlier with persisting GI symptoms were randomised to management according to the algorithm by 1. a GI nurse or 2. gastroenterologist or 3. the self help Macmillan booklet “Pelvic Radiotherapy: Possible Late Effects”. After 6 months, booklet arm patients with persisting symptoms could ask to see the gastroenterologist. Patients in the nurse arm were transferred to the gastroenterologist if they had problems beyond the algorithm’s scope. The primary end point was change in the modified Inflammatory Bowel Disease Questionnaire – bowel sub score (IBDQ-B) at 6 months. Follow up continued until 12 months. The trial had 80% power to answer the 1st hypothesis after randomising 196 patients and the 2ndafter closing the booklet arm, and randomising 22 more patients to gastroenterologist or nurse. <h3>Results</h3> 168 men, median age 70 (range 34 – 83), 50 women median age 61 (29 – 87), 28 treated for GI, 34 gynaecological &amp; 156 urological cancer were randomised to booklet (n = 68), nurse (n = 80) or gastroenterologist (n = 70). 30 (44%) from the booklet and 4 (5%) from the nurse arm crossed to the gastroenterologist. Groups were well balanced for baseline scores and patient characteristics. 66.5% of patients had a baseline IBDQ-B score indicating moderate/severe symptoms. Intention to treat analysis showed a mean improvement in IBDQ-B score in the booklet arm of 4.9 (95% CIs 1.4–8.4), in the nurse arm 8.8 (6.9–11.2) and 10.3 (7.7–13.1) in the gastroenterologist arm. Improvement in IBDQ-B score was both clinically and statistically significant (compared to booklet) in the nurse (p = 0.04), gastroenterologist (p = 0.014) and combined treatment arms (p = 0.006). Outcomes in the nurse treated arm were not worse than those treated by the gastroenterologist (p = 0.428). Improvements were sustained over time. <h3>Conclusion</h3> Targeted intervention following a detailed clinical algorithm can significantly ameliorate radiotherapy-induced GI symptoms. Most patients can be managed by a suitably trained and supported nurse. (Funding RfPB, NIHR) <h3>Disclosure of Interest</h3> None Declared
Noradrenaline: a circulating inhibitor of sodium transport.
Authors: A Riozzi, A M Heagerty, R F Bing, H Thurston, J D Swales
Journal: BMJ (1984)

Leucocytes were isolated from venous blood of 11 normotensive volunteers with no family history of hypertension and the sodium efflux rate constants determined both alone and in the presence of increasing physiological concentrations of noradrenaline. There was a significant dose dependent reduction of total sodium efflux rate constant due to a reduction in ouabain sensitive sodium pump activity, glycoside insensitive efflux rate constants being unaffected. The magnitude of this effect was similar to the reduction in leucocyte sodium efflux rate constants observed in hypertensive patients (and their normotensive relatives). The noradrenaline induced depression of sodium pump activity was prevented by propranolol in a further seven experiments, suggesting that the effect was mediated by beta adrenoceptors. Catecholamines possibly functioning as circulating inhibitors of sodium transport may contribute to some of the disturbances in membrane electrolyte handling both in essential hypertension in man and in some experimental models of hypertension.
Timing of Tracheostomy—Reply
Authors: Duncan Young
Journal: JAMA (2013)

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CORPUS LUTEUM THERAPY
Authors: GEORGE W. CORNER
Journal: JAMA (1935)

<h3>Note.</h3> —These articles and the articles in the previous issues ofThe Journalare part of a series published under the auspices of the Council on Pharmacy and Chemistry. Other articles will appear in succeeding issues. When' completed, the series will be published in book form.—Ed. The title of this article, "corpus luteum therapy," of course indicates scarcely more than a hope for the future; I am sadly aware that its perusal cannot immediately result in curative benefit to a single patient. Nevertheless it will be profitable to consider the subject as it stands today, from the mutual standpoint of the practitioner and the investigator. Such consideration will not only explain the physiologic basis on which practical applications are to be worked out but also help, it is hoped, to clear away the misconceptions and false hopes by reason of which in the past so many bottles and pill boxes
Myosin at the Heart of the Problem
Authors: Jil C. Tardiff
Journal: New England Journal of Medicine (2004)

In humans, myosins comprise a superfamily of more than 30 individual proteins. Structurally, myosin contains a highly conserved globular head, which, in turn, contains the ATPase and actin-binding sites, and a rod-like tail that modulates assembly and protein–protein interactions. Although the role of myosin as the molecular motor that drives striated-muscle contraction is well understood, myosins are also found in virtually all eukaryotic cells, where they are involved in a broad range of intracellular functions, including organelle transport, endocytosis, cytokinesis, and cytoskeletal support. In the past 10 years, research in a number of fields has revealed many of the underlying . . .
Lactate Dehydrogenase Isoenzymes in Alveolar Proteinosis
Authors: Francis F. Fountain
Journal: JAMA (1969)

<h3>To the Editor:—</h3> Pulmonary alveolar proteinosis is a disease of unknown etiology, the active phase of which is marked by an increase in total serum lactate dehydrogenase ( LDH) level.<sup>1-3</sup>Despite the many reports which document the increased total LDH level in the serum and despite an extensive review of the English literature on the subject, I have been unable to find reports of isoenzymes of LDH. Recently, however, in performing a pulmonary lavage on a patient with alveolar proteinosis, we had an opportunity to record the LDH isoenzymes in the lavage effluent as well as in the serum before lavage. <h3>Report of a Case:—</h3> A 61-year-old Negro man was admitted to the West Tennessee Chest Disease Hospital with increasing dyspnea and diffuse pulmonary infiltrates bilaterally. Review of yearly roentgenograms of the chest showed the disease to have started one year prior to admission. Numerous examinations of sputum for mycobacterial,
PWE-117 Prevalence of Falls in the Uk PBC Population
Authors: L Griffiths, J Newton, D Jones
Journal: Gut (2013)

<h3>Introduction</h3> Previous studies have documented the prevalence of falls in PBC in a geographical area but there is no published data on the prevalence of falls in a national UK PBC cohort. Prevalence of falls was reported as 70% in the Newcastle-upon-Tyne cohort. Risk factors for falls are known to be prevalent in people with PBC, particularly autonomic dysfunction and lower limb muscle weakness and combined with the high prevalence of osteoporosis this carries a significant risk to the patient from falls and falls related injuries with the associated healthcare and financial implications. This study aimed to assess the prevalence of falls in the National PBC cohort as well as associated falls related injuries and related hospital admissions. We also explored the relationship between falls and autonomic symptoms. <h3>Methods</h3> Symptom assessment tools were completed by patients as part of the UKPBC genetics study. Information about falls and associated injuries was collected using a standardised data capture tool and autonomic symptoms were quantified using the Orthostatic Grading Score. <h3>Results</h3> Data was collected on 2328 patients with PBC from all around the UK. 862 (37%) of PBC patients had fallen, 118 (8%) were current fallers (one fall within the past year) and 414 (17.7%) were recurrent fallers (more than one fall in the past year). 35% of patients attended A&amp;E following their fall with 9.7% of fallers requiring admission as a consequence of their fall and 24% of PBC patients who fell sustained a fracture. Fallers were significantly more likely to be diabetic (diabetes present in 5.7% of non-fallers and 12.2% of fallers, p &lt; 0.0001) and more likely to be taking cardioactive medication (29% in non-fallers and 71% in fallers, p &lt; 0.0001). Autonomic symptoms were significantly more prevalent in those PBC patients with recurrent falls (mean OGS 5.44, SD 4.15) compared to non-fallers (mean OGS 2.38, SD 2.13)and infrequent fallers (mean OGS 3.2, SD 3.36) p &lt; 0.0001. <h3>Conclusion</h3> A significant percentage of patients with PBC are falling, sustaining fractures and being admitted to hospital following a fall. This has huge implications for patients with PBC in terms of morbidity, mortality and quality of life. The high prevalence of autonomic symptoms in the population that fall demonstrate the importance of considering this symptom in all PBC patients as there are a number of interventions that can be implemented. Patients that fall often have more than one risk factor and this study demonstrated this as autonomic symptoms, diabetes and the presence of cardioactive medications were all more common in the cohort of fallers therefore all patients with PBC need a careful assessment for the presence of falls risk factors and a multidisciplinary approach to reduce the risk of falls. <h3>Disclosure of Interest</h3> None Declared.
Use of dual intracoronary scintigraphy with thallium-201 and technetium-99m pyrophosphate to predict improvement in left ventricular wall motion immediately after intracoronary thrombolysis in acute myocardial infarction
Authors: Joachim Schofer, Detlef G. Mathey, Ricardo Montz, Walter Bleifeld, Peter Stritzke
Journal: Journal of the American College of Cardiology (1983)
Abstract 2991: Glucose deprivation induces Chk1 degradation through the ubiquitin-proteasome pathway and defective checkpoint response to replication blocks
Authors: Ae Jeong Kim, Hyun-Ju Kim, Hye Jin Jee, Yoe-Sik Bae, Jeanho Yun
Journal: Cancer Research (2010)

Abstract Chk1 is a key regulator for DNA replication checkpoint and preservation of genomic integrity. Previous studies showed that reduction of Chk1 function leads to defect in checkpoint response and closely associated to tumorigenesis. Here, we found that Chk1 protein is rapidly degraded upon glucose deprivation while its mRNA level is not changed. The glucose deprivation-induced Chk1 degradation is observed in various cancer cell lines as well as human normal fibroblast therefore appears to be a universal phenomenon in mammalian cells. Specific proteasome inhibitor blocks glucose deprivation-induced degradation of Chk1, and the ubiquitination of Chk1 is induced, indicating that the proteasome-ubiquitin pathway mediates the degradation of Chk1. Glucose deprivation-induced Chk1 degradation was not affected by AMPK inhibitor compound C or antioxidant NAC and GSH treatment. Instead, we found that Chk1 phosphorylation at Ser317 and Ser345 site were important step for degradation of Chk1 in response to glucose deprivation. In glucose deprivation condition, cells showed defective checkpoint response to replication stresses, camptothecin (CPT) and hydroxyurea (HU) treatment. Taken together, our results suggest that Chk1 function is suppressed through the ubiquitin-mediated proteolysis in glucose deprivation condition and thereby results in inactivation of proper checkpoint function. Glucose deprivation-induced Chk1 degradation could cause defect in maintaining DNA integrity and may contribute to tumor development in tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2991.
Hypertension: comparison of drug and non-drug treatments.
Authors: G Andrews, S W MacMahon, A Austin, D G Byrne
Journal: BMJ (1982)

Thirty-seven reports of the treatment of hypertension by non-pharmacological means were compared with the results of treatment by standard drug regimens. Treatment by drugs produced the greatest lowering of blood pressure. Treatment by weight reduction, yoga, and muscle relaxation each produced smaller, but appreciable, changes in blood pressure biofeedback, and salt restriction were inferior to those of the other regimens and were not significantly different to the effects of placebo treatment. Large comparative trials of pharmacological and non-pharmacological treatments are needed before definite conclusions can be made.