tbuckley/cabot-search huggingface dataset:
Cholecystokinin octapeptide stimulates phasic and tonic pyloric motility in healthy humans.
Authors: R Fraser, D Fone, M Horowitz, J Dent
Journal: Gut (1993)

Stimulation of localised pyloric contractions may be an important mechanism in the slowing of gastric emptying by cholecystokinin infusion. The effect of cholecystokinin octapeptide on fasting pyloric motility was investigated in 14 healthy volunteers. Antral, pyloric, and duodenal pressure responses to normal saline and graded injections of cholecystokinin octapeptide (5, 10, and 20 ng/kg) were measured. Injections were given double blind and in randomised order. All doses of cholecystokinin octapeptide initially stimulated (p &lt; 0.05 cf saline) phasic pressure waves localised to the pylorus--the median number of pyloric pressure waves in the 5 minutes after injection being 0, 3.5, 6, and 7 for the saline and the 5, 10, 20 ng/kg cholecystokinin octapeptide injections respectively. The phasic pyloric motor response to 20 ng/kg cholecystokinin octapeptide injection was greater than that to 5 ng/kg (p &lt; 0.05). Basal pyloric pressure increased after 20 ng/kg (1.0 v 0.2 mm Hg, p &lt; 0.05 cf saline). Antral and duodenal pressure waves were suppressed initially by all doses of cholecystokinin (p &lt; 0.05 cf saline). Subsequently, 20 of the 42 cholecystokinin octapeptide, injections but none of the saline injections, were followed by antropyloric pressure waves. Atropine, 15 micrograms/kg iv as a bolus, and then 4 micrograms/kg/hour iv as an infusion, had no effect on the stimulation of localised phasic pyloric pressure waves by cholecystokinin octapeptide 10 ng/kg. It is concluded that stimulation of pyloric contractions and suppression of antral and proximal duodenal motility may contribute to the slowing of gastric emptying produced by cholecystokinin.
Use of Whole-Genome Sequencing to Diagnose a Cryptic Fusion Oncogene
Authors: John S. Welch
Journal: JAMA (2011)

Whole-genome sequencing is becoming increasingly available for research purposes, but it has not yet been routinely used for clinical diagnosis.To determine whether whole-genome sequencing can identify cryptic, actionable mutations in a clinically relevant time frame.We were referred a difficult diagnostic case of acute promyelocytic leukemia with no pathogenic X-RARA fusion identified by routine metaphase cytogenetics or interphase fluorescence in situ hybridization (FISH). The case patient was enrolled in an institutional review board-approved protocol, with consent specifically tailored to the implications of whole-genome sequencing. The protocol uses a "movable firewall" that maintains patient anonymity within the entire research team but allows the research team to communicate medically relevant information to the treating physician.Clinical relevance of whole-genome sequencing and time to communicate validated results to the treating physician.Massively parallel paired-end sequencing allowed identification of a cytogenetically cryptic event: a 77-kilobase segment from chromosome 15 was inserted en bloc into the second intron of the RARA gene on chromosome 17, resulting in a classic bcr3 PML-RARA fusion gene. Reverse transcription polymerase chain reaction sequencing subsequently validated the expression of the fusion transcript. Novel FISH probes identified 2 additional cases of t(15;17)-negative acute promyelocytic leukemia that had cytogenetically invisible insertions. Whole-genome sequencing and validation were completed in 7 weeks and changed the treatment plan for the patient.Whole-genome sequencing can identify cytogenetically invisible oncogenes in a clinically relevant time frame.
The difficulty in evaluating all findings in study on use of macrolides in mother and child and risk of infantile hypertrophic pyloric stenosis
Authors: F. de Vries
Journal: BMJ (2014)

Lund and colleagues report a 30-fold risk of infantile hypertrophic pyloric stenosis with the use of macrolide antibiotics during the first 0-13 days of a child's life. 1 This is either a very strong association or too good to be true.
Clinically Used Breast Cancer Markers Such As Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2 Are Unstable Throughout Tumor Progression
Authors: Linda Sofie Lindström, Eva Karlsson, Ulla M. Wilking, Ulla Johansson, Johan Hartman, Elisabet Kerstin Lidbrink, Thomas Hatschek, Lambert Skoog, Jonas Bergh
Journal: Journal of Clinical Oncology (2012)

PURPOSE To investigate whether hormonal receptors and human epidermal growth factor receptor 2 (HER2) change throughout tumor progression, because this may alter patient management. PATIENTS AND METHODS The study cohort included female patients with breast cancer in the Stockholm health care region who relapsed from January 1, 1997, to December 31, 2007. Either biochemical or immunohistochemical (IHC)/immunocytochemical (ICC) methods were used to determine estrogen receptor (ER), progesterone receptor (PR), and HER2 status, which was then confirmed by fluorescent in situ hybridization for IHC/ICC 2+ and 3+ status. Results ER (459 patients), PR (430 patients), and HER2 (104 patients) from both primary tumor and relapse were assessed, revealing a change in 32.4% (McNemar's test P < .001), 40.7% (P < .001), and 14.5% (P = .44) of patients, respectively. Assessment of ER (119 patients), PR (116 patients), and HER2 (32 patients) with multiple (from two to six) consecutive relapses showed an alteration in 33.6%, 32.0%, and 15.7% of patients, respectively. A statistically significant differential overall survival related to intraindividual ER and PR status in primary tumor and relapse (log-rank P < .001) was noted. In addition, women with ER-positive primary tumors that changed to ER-negative tumors had a significant 48% increased risk of death (hazard ratio, 1.48; 95% CI, 1.08 to 2.05) compared with women with stable ER-positive tumors. CONCLUSION Patients with breast cancer experience altered hormone receptor and HER2 status throughout tumor progression, possibly influenced by adjuvant therapies, which significantly influences survival. Hence, marker investigations at relapse may potentially improve patient management and survival.
Patients give NHS vote of confidence
Authors: Adrian O'Dowd
Journal: BMJ (2007)

An influential group of MPs has claimed that widespread financial incompetence is adding to the cost of the United Kingdom's controversial private finance initiative (PFI).The House of Commons Committee of Public Accounts made its new attack on the PFI after it discovered that the government had clawed back £100m (€145m; $200m) less than was predicted from the new private-public profit sharing schemes.The committee's chairman, the Conservative MP Edward Leigh, blamed the loss on the failure of Treasury officials to oversee key refinancing arrangements.In 2002 ministers introduced changes so that public sector bodies could share in some of the financial gains when big PFI loans were rearranged.Typically, these loans were renegotiated on a more favourable basis once PFI projects had been completed and the risks involved were lower.However, left to their own devices, officials in local hospitals had been out of their depth negotiating with their counterparts in the private sector, the committee says.In 2003 the Office of Government Commerce, which then had responsibility for PFI policy, told the public accounts committee that it expected the public sector to receive between £175m and £200m from the voluntary sharing arrangements in early PFI deals.However, up to December 2006 the government had secured the right to gains of only £93m."Proceeds gained by the public sector from PFI debt refinancing under the voluntary code for the sharing of gains are currently well short of expectations" said Mr Leigh.
Reduced striatal volumes in Parkinson’s disease: a magnetic resonance imaging study
Authors: Toni L Pitcher, Tracy R Melzer, Michael R MacAskill, Charlotte F Graham, Leslie Livingston, Ross J Keenan, Richard Watts, John C Dalrymple-Alford, Tim J Anderson
Journal: Translational Neurodegeneration (2012)

The presence and extent of structural changes in the brain as a consequence of Parkinson's disease (PD) is still poorly understood. High-resolution 3-tesla T1-weighted structural magnetic resonance images in sixty-five PD and 27 age-matched healthy control participants were examined. Putamen, caudate, and intracranial volumes were manually traced in the axial plane of 3D reconstructed images. Striatal nuclei volumes were normalized to intracranial volume for statistical comparison. Disease status was assessed using the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr scale. Cognitive status was assessed using global status tests and detailed neuropsychological testing. Both caudate and putamen volumes were smaller in PD brains compared to controls after adjusting for age and gender. Caudate volumes were reduced by 11% (p = 0.001) and putamen volumes by 8.1% (p = 0.025). PD striatal volumes were not found to be significantly correlated with cognitive or motor decline. Small, but significant reductions in the volume of both the caudate and putamen occur in PD brains. These reductions are independent of the effects of age and gender, however the relation of these reductions to the functional loss of dopamine, which is characteristic of PD, remains unclear.
Survival benefit with imatinib mesylate versus interferon-α–based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia
Authors: Hagop M. Kantarjian, Moshe Talpaz, Susan O'Brien, Daniel Jones, Francis Giles, Guillermo Garcia-Manero, Stefan Faderl, Farhad Ravandi, Mary Beth Rios, Jianqin Shan, Jorge Cortes
Journal: Blood (2006)
Favorable Outcome for Adolescents With Acute Lymphoblastic Leukemia Treated on Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocols
Authors: Elly Barry, Daniel J. DeAngelo, Donna Neuberg, Kristen Stevenson, Mignon L. Loh, Barbara L. Asselin, Ronald D. Barr, Luis A. Clavell, Craig A. Hurwitz, Albert Moghrabi, Yvan Samson, Marshall Schorin, Harvey J. Cohen, Stephen E. Sallan, Lewis B. Silverman
Journal: Journal of Clinical Oncology (2007)

Historically, adolescents with acute lymphoblastic leukemia (ALL) have had inferior outcomes when compared with younger children. We report the outcome of adolescents treated on Dana-Farber Cancer Institute (DFCI; Boston, MA) ALL Consortium Protocols conducted between 1991 and 2000.A total of 844 patients aged 1 to 18 years, with newly diagnosed ALL were enrolled onto two consecutive DFCI-ALL Consortium Protocols. We compared outcomes in three age groups: children aged 1 to 10 years (n = 685), young adolescents aged 10 to 15 years (n = 108), and older adolescents aged 15 to 18 years (n = 51).With a median follow-up of 6.5 years, the 5-year event-free survival (EFS) for those aged 1 to 10 years was 85% (SE, 1%), compared with 77% (SE, 4%) for those aged 10 to 15 years, and 78% (SE, 6%) for those aged 15 to 18 years (P = .09). Adolescents were more likely to present with T-cell phenotype (P < .001) and less likely to have the TEL-AML1 fusion (P = .05). The incidence of pancreatitis and thromboembolic complications, but not asparaginase allergy, was higher in patients 10 years of age compared with those younger than 10 years. However, there was no difference in the rate of treatment-related complications between the 10- to 15-year and 15- to 18-year age groups.Adolescents were more likely to present at diagnosis with biologically higher risk disease (T-cell phenotype and absence of the TEL-AML1 fusion) and more likely to experience treatment-related complications than younger children. However, the 5-year EFS for older adolescents was 78% +/- 6%, which is superior to published outcomes for similarly aged patients treated with other pediatric and adult ALL regimens. Based on this experience, we currently are piloting our regimen in patients aged 18 to 50 years.
Cardiac Safety of Budesonide (BUD)/Formoterol (FM) Pressurized Metered-Dose Inhaler (pMDI): Pooled Data From Clinical Studies of Children, Adolescents, and Adults With Asthma
Authors: S PETERS, L ROSENWASSER, P VERVAET, C OBRIEN
Journal: Journal of Allergy and Clinical Immunology (2008)

To assess the cardiac safety of BUD/FM pMDI in a large population of asthma patients undergoing ECG evaluation. Postdose and untimed cardiac data from 6 active- and placebo-controlled US studies (12-26 weeks) in asthma patients ≥6 years were pooled. Treatments included BUD/FM pMDI ([80/4.5μg ×2 inhalations (160/9μg) qd to 160/4.5μg ×2 inhalations (320/9μg) bid]; n = 1309), BUD pMDI or DPI ([80μg ×2 inhalations (160μg) qd to 160μg ×2 inhalations (320μg) bid]; n = 758), FM DPI ([4.5μg ×2 inhalations (9μg) bid]; n = 384), and placebo (n = 409). Mean changes from baseline to treatment maximum and shifts in postdose and untimed ECGs were assessed. For postdose ECGs, statistically significant (P ≤ .021), but not clinically meaningful, increases in heart rate, QTc (Baz), and QTc (Frid) were observed with BUD/FM (4.3 bpm, 15.3 msec, 15.2 msec, respectively) versus BUD (3.0 bpm, 12.0 msec, 13.3 msec) and placebo (2.2 bpm, 10.2 msec, 10.9 msec) but not FM (5.5 bpm, 14.7 msec, 13.8 msec). Percentages of patients with heart rate >100 bpm or an increase ≥20 bpm were slightly higher for BUD/FM (8.9%) versus BUD (5.9%) and placebo (4.2%), but lower than FM (12.5%). Percentages of patients with QT, QTc (Baz), or QTc (Frid) ≥500 msec or an increase ≥60 msec were low (BUD/FM, 2.9%, 2.5%, 1.2%; BUD, 4.1%, 1.4%, 0.7%; FM, 1.8%, 1.3%, 0.8%; placebo, 2.3%, 0.7%, 0%). Results were generally similar when all ECGs were considered. BUD/FM pMDI demonstrated an electrocardiographic safety profile similar to FM, with no clinically meaningful differences versus BUD, in this large patient population.
The Dutch Hypothesis Meets Genomics
Authors: Scott T. Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Obesity and allergic asthma are complex processes in which many complementary and synergistic pathways contribute to clinical manifestations of disease.The current article suggests that a common factor can lead to the pathogenesis of both, as well as suggesting the appealing idea that intervention in the Sirt1-Chi3l1 pathway may simultaneously intervene in obesity and allergic asthma.Although pharmacologic approaches are attractive, the effect of dietary manipulation is of great interest.There is precedent to suggest a high-fat diet can affect airway inflammation: Wood and colleagues have reported that a high-fat meal can increase airway neutrophilic inflammation and decrease bronchodilator responsiveness in asthma ( 16).It will be of great interest to know whether dietary manipulation or other means of weight control could affect allergic asthma outcomes in obese people, analogous to the effects in mice from pharmacologic and genetic approaches targeting the Sirt1-Chi3l1 pathway.
Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss
Authors: Jost Schönberger, Libin Wang, Jordan T Shin, Sang Do Kim, Frederic F S Depreux, Hao Zhu, Leonard Zon, Anne Pizard, Jae B Kim, Calum A MacRae, Andy J Mungall, J G Seidman, Christine E Seidman
Journal: Nature Genetics (2005)
Bacterial endocarditis presenting as acute monoarthritis.
Authors: A Doube, A Calin
Journal: Annals of the Rheumatic Diseases (1988)

The presentation of a pig farmer with acute arthritis of the shoulder, cardiac murmurs, and Streptococcus suis growing on blood cultures highlights one of the rheumatological presentations of bacterial endocarditis. The need for a thorough general medical examination together with synovial fluid and blood culture in patients with acute monarthritis is emphasised. The suggestion that acute arthritis related to endocarditis is in nature truly septic, rather than mediated by circulating immune complexes, is supported.
Controlled trial of oligopeptide versus amino acid diet in treatment of active Crohn's disease.
Authors: J C Mansfield, M H Giaffer, C D Holdsworth
Journal: Gut (1995)

Elemental diets are effective in inducing remission in active Crohn9s disease, but how they exert this therapeutic effect is unclear. In a previous study a whole protein containing diet proved less effective than one in which food antigens were excluded, suggesting that exclusion of food antigens from the gut was a possible mechanism. This study was designed to test whether an oligopeptide diet of hydrolysed proteins was as effective as an amino acid based diet. These diets were equally antigen free but with different nitrogen sources. Forty four patients with active Crohn9s disease were randomised in a controlled trial of amino acid versus oligopeptide diet. The feeds were given by nasogastric tube in equicaloric quantities and were the sole form of nutrition. Treatment was continued for four weeks although failure to improve by day 10 resulted in withdrawal. Quantitative leucocyte scintigraphy was used to investigate the effect of diet treatment on gut inflammation. Clinical and nutritional responses to treatment were also measured. Sixteen patients entered remission (including withdrawal of corticosteroids), six patients could not tolerate the nasogastric tube, and 22 patients failed to respond. The two diets were equally effective. Patients who responded had a rapid drop in clinical index of disease activity and a major reduction in the bowel uptake of leucocytes on scintigraphy. The oligopeptide and amino acid based enteral feeds were equally effective at inducing remission in active Crohn9s disease. With both diets clinical improvement was accompanied by a reduction in intestinal inflammation.
Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial
Authors: Kirsti Näntö-Salonen, Antti Kupila, Satu Simell, Heli Siljander, Tiina Salonsaari, Anne Hekkala, Sari Korhonen, Risto Erkkola, Jukka I Sipilä, Lotta Haavisto, Marja Siltala, Juhani Tuominen, Jari Hakalax, Heikki Hyöty, Jorma Ilonen, Riitta Veijola, Tuula Simell, Mikael Knip, Olli Simell
Journal: The Lancet (2008)
Human Neural Stem Cells Induce Functional Myelination in Mice with Severe Dysmyelination
Authors: Nobuko Uchida, Kevin Chen, Monika Dohse, Kelly D. Hansen, Justin Dean, Joshua R. Buser, Art Riddle, Douglas J. Beardsley, Ying Wan, Xi Gong, Thuan Nguyen, Brian J. Cummings, Aileen J. Anderson, Stanley J. Tamaki, Ann Tsukamoto, Irving L. Weissman, Steven G. Matsumoto, Larry S. Sherman, Christopher D. Kroenke, Stephen A. Back
Journal: Science Translational Medicine (2012)

Shiverer-immunodeficient (Shi-id) mice demonstrate defective myelination in the central nervous system (CNS) and significant ataxia by 2 to 3 weeks of life. Expanded, banked human neural stem cells (HuCNS-SCs) were transplanted into three sites in the brains of neonatal or juvenile Shi-id mice, which were asymptomatic or showed advanced hypomyelination, respectively. In both groups of mice, HuCNS-SCs engrafted and underwent preferential differentiation into oligodendrocytes. These oligodendrocytes generated compact myelin with normalized nodal organization, ultrastructure, and axon conduction velocities. Myelination was equivalent in neonatal and juvenile mice by quantitative histopathology and high-field ex vivo magnetic resonance imaging, which, through fractional anisotropy, revealed CNS myelination 5 to 7 weeks after HuCNS-SC transplantation. Transplanted HuCNS-SCs generated functional myelin in the CNS, even in animals with severe symptomatic hypomyelination, suggesting that this strategy may be useful for treating dysmyelinating diseases.
Clinical leadership category: Enthusing, negotiating, pacifying--all part of a leader's work
Authors: C. M. a. H. M. B. Learning
Journal: BMJ (2010)

“Clinical leadership is at the core of delivering a patient led NHS. In order to improve local services it is crucial that the clinicians who deliver these services are instrumental in their transformation.” The words of Sir Bruce Keogh, NHS Medical Director, describe the importance that those at the top of the NHS place on it. It is clear from the entries that we received for the BMJ Group Clinical Leadership award that healthcare professionals in the NHS have risen to the challenge.

Clinical leadership requires dedication. Clinicians are being asked to respond to a range of challenges: investment is slowing down, and demands for quality, safety, and efficiency are rising. Strategic plans from health authorities and trusts are identifying key areas for service redesign and improvement. Clinical leaders are standing in the gap between management and their clinical colleagues—enthusing, negotiating, pacifying, and challenging are all part of a day’s work.

Against this background, we reviewed the many excellent submissions, looking for clinicians who have gone “over and above” their normal duties to show excellence in clinical leadership on the frontline. This award is about leadership combined with …
Remarks on the Progress of Helminthology, and on Dr. Haussmann's Observations respecting Taenia in Infants
Authors: T. S. Cobbold
Journal: BMJ (1872)

accurate conception of the form of the curved surface may be gaine( from the curves of the three series of experiments that have beei made.The region included within this curved surface represents every pos sible variation in the doses of atropia and physostigma, and in the intervals of time separating the administration of the two substances, that is compatible with the production of successful antagonism be, tween physostigma and atropia.Its existence shows us how an inves.tigation on antagonism may lead to very fallacious results, even wher every care has been taken in obtaining a large amount of experimental data.I have already pointed out that, almost without exception, the instances of lethal antagonism asserted to exist cannot be regarded as certainly established, because sufficient care has not been taken in proving that recovery took place after an undoubtedly lethal dose ol *one of the substances concerned.In attempting to disprove the exist- ence of any asserted instance of lethal antagonism, a fallacy of equal importance may originate from ignorance of the fact that the antago.nism does not necessarily occur throughout an unlimited range in the doses of the two substances, or in the intervals of time separating their administration: in short, that there is a region of death as well as a region of recovery in connection with probably every instance of lethal ;antagonism.Unless, therefore, the factors I have mentioned be greatly varied in a large series of experiments, it cannot be positively asserted that the antagonism does not exist.It appears to me that the fallacy to which I have now drawn your attention, has not been sufficiently attended to in much that has recently been written on the subject of antagonism.Bearing ofAntagonism between Active Substances on Therapeutics.-