tbuckley/cabot-search huggingface dataset:
THE DIVERSION OF THE PANCREATIC JUICE FROM THE DUODENUM INTO THE STOMACH. ITS EFFECTS UPON THE LEVEL OF GASTRIC ACIDITY AND UPON THE PANCREAS
Authors: Ernest G. Grey
Journal: The Journal of Experimental Medicine (1917)

The mechanism described for maintaining the optimum level of gastric acidity is designated by Boldyreff as the "self regulation of the acidity of the contents of the stomach." In support of Boldyreff's hypothesis is the evidence obtained from many experiments carried out both on man and on animals, in which solutions of alkali and acid have been placed in the stomach. The introduction of acid fluid has led to a regurgitation of alkaline duodenal contents, whereas the introduction of alkaline solutions has called forth a secretion of acid gastric juice. The experiments reported in this paper were carried out for the purpose of ascertaining how the stomach would react, in as far as the secretion of hydrochloric acid is concerned, to a more or less continuous influx of relatively strong alkaline fluid, prolonged throughout the cycle of digestion. Numerous studies have shown that any serious interference with the process of regurgitation leads to a rise in the acidity level of the stomach; i.e., to a state of hyperacidity. There is but little evidence, however, to indicate whether the acidity level will be depressed temporarily or permanently (hypoacidity) when alkaline material, in considerable amounts, continues to enter the stomach. The influx of alkaline fluid was provided for by transplanting the larger pancreatic duct into the wall of the stomach after ligating and dividing the lesser duct. Specimens of test meal for analysis were withdrawn through gastric fistulas made after the method of Janeway. Animals prepared in this manner served also to furnish additional information regarding the possible relation of the hydrochloric acid of the gastric juice to certain acute inflammatory and chronic sclerotic changes in the pancreas. From the results of these experiments it appears that the presence of a considerable amount of pancreatic juice in the stomach throughout the period of digestion leads only to a moderate decrease in the acidity level of the ingesta in the later stages of digestion. Earlier in the process there is no constant alteration of the acidity level in either direction. The findings then serve not only to corroborate the views of Boldyreff, but also to demonstrate the remarkable compensatory activity of the gastric glands under conditions which entail an unusual quantity of alkali in the stomach. In addition the work has shown that when the larger pancreatic duct is properly transplanted into the wall of the stomach, it may remain patent for months. In animals in which this operative procedure has been carried out, the pancreas has been found to undergo no inflammatory or other degenerative changes. This finding is regarded as evidence against the postulation of Hlava that gastric juice is probably responsible for the occurrence of certain cases of acute hemorrhagic pancreatitis.
Biallelic Deletions in <i>INK4</i> in Cutaneous Melanoma Are Common and Associated with Decreased Survival
Authors: Eva Grafström, Suzanne Egyházi, Ulrik Ringborg, Johan Hansson, Anton Platz
Journal: Clinical Cancer Research (2005)

Both the retinoblastoma and p53 pathways are often genetically altered in human cancers and their complex regulation is in part mediated by the three gene products p16, p14(ARF), and p15 of the INK4 locus on chromosome 9p21. Partial or complete biallelic deletions of the INK4 locus have been recognized in a variety of malignant tumors, including malignant melanoma. We have in the present study measured the frequency of INK4 deletions in a large number of melanoma metastases and determined their association with clinicopathologic variables and survival data.Quantitative real-time PCR, as well as fluorescence-based fragment analysis, has been used to perform measurements of the relative allelic concentrations of the INK4 genes in 112 human melanoma tumor samples from 86 patients.Thirty-eight of 86 melanoma patients (44%) had metastases with biallelic losses in INK4. Ten of 20 patients with multiple metastases showed similar deletion patterns in all analyzed tumors. There was no significant association between any of the clinicopathologic variables and loss of INK4. However, loss of INK4 had an adverse effect on median survival from time of diagnosis. Patients with tumors with diploid INK4 had a median survival of 142 months, whereas those with monoallelic or biallelic loss in INK4 had a median survival of only 47 months (P = 0.006).Our results point to homozygous deletions in the INK4 region as being one of the most common genetic alterations in malignant cutaneous melanoma. INK4 deletions are associated with an adverse prognosis.
Baroreflex control of muscle sympathetic nerve activity in borderline hypertension.
Authors: R F Rea, M Hamdan
Journal: Circulation (1990)

Patients with borderline hypertension have exaggerated vascular responses to orthostatic stress produced by tilt or lower body negative pressure (LBNP). It has been suggested that 1) in the supine position, these patients have augmented activity of cardiopulmonary baroreceptors that exerts an increased restraint on sympathetic vasoconstrictor tone; 2) withdrawal of this augmented inhibitory baroreceptor activity during orthostatic stress elicits augmented reflex sympathetic vasoconstrictor outflow; and 3) augmented cardiopulmonary baroreceptor activity may be secondary to impaired arterial baroreflex mechanisms. To test these hypotheses, we recorded muscle sympathetic nerve activity from the peroneal nerve in seven borderline hypertensive subjects and seven age-, sex-, and weight-matched normotensive subjects during three levels of nonhypotensive LBNP and infusions of phenylephrine and nitroprusside. During LBNP, reductions of central venous pressure were similar in borderline hypertensive and normotensive subjects, and arterial pressure and heart rate values were unchanged. Increases of sympathetic nerve activity, however, were significantly greater in borderline hypertensive than in normotensive subjects at each level of LBNP, indicating an augmented gain of the cardiopulmonary baroreflex. To determine whether this augmentation is related to impairment of arterial baroreflexes, we measured changes of sympathetic nerve activity during increases and decreases of arterial pressure produced with infusions of intravenous phenylephrine and nitroprusside. Central venous pressure was held at control levels by LBNP during phenylephrine and saline infusion during nitroprusside. Changes of sympathetic nerve activity during alterations of arterial pressure were similar in borderline hypertensive and normotensive subjects. These data show that cardiopulmonary baroreflex control of SNA is augmented in borderline hypertensive subjects and that this augmentation does not result from an attenuation of the arterial baroreflex.
Attractor Dynamics of Spatially Correlated Neural Activity in the Limbic System
Authors: James J. Knierim, Kechen Zhang
Journal: Annual Review of Neuroscience (2012)

Attractor networks are a popular computational construct used to model different brain systems. These networks allow elegant computations that are thought to represent a number of aspects of brain function. Although there is good reason to believe that the brain displays attractor dynamics, it has proven difficult to test experimentally whether any particular attractor architecture resides in any particular brain circuit. We review models and experimental evidence for three systems in the rat brain that are presumed to be components of the rat's navigational and memory system. Head-direction cells have been modeled as a ring attractor, grid cells as a plane attractor, and place cells both as a plane attractor and as a point attractor. Whereas the models have proven to be extremely useful conceptual tools, the experimental evidence in their favor, although intriguing, is still mostly circumstantial.
Physical and Psychosocial Recovery in the Year After Primary Treatment of Breast Cancer
Authors: Patricia A. Ganz, Lorna Kwan, Annette L. Stanton, Julienne E. Bower, Thomas R. Belin
Journal: Journal of Clinical Oncology (2011)

Purpose The 2000 National Institutes of Health Consensus Conference on Adjuvant Therapy of Breast Cancer recommended chemotherapy for all women with invasive cancer greater than 1 centimeter. Studies of long-term breast cancer survivors have found poorer quality of life (QOL) in women who received adjuvant chemotherapy. The aim of this article is to characterize physical and psychosocial recovery as a function of chemotherapy receipt in the year after medical treatment completion. Patients and Methods Prospective longitudinal survey data (RAND SF-36 and Breast Cancer Prevention Trial [BCPT] Symptom Scales) collected from 558 women with breast cancer enrolled on the Moving Beyond Cancer (MBC) psychoeducational intervention trial were compared according to receipt of chemotherapy. MBC study enrollment occurred within 4 weeks after the end of primary treatment (eg, surgery, chemotherapy, radiation). Self-report questionnaire data collected at enrollment and at 2, 6, and 12 months thereafter were examined, controlling for intervention and with propensity score adjustment for imbalance of covariates. Outcome analyses were carried out by fitting linear mixed models by using SAS PROC MIXED. Results Longitudinal SF-36 scale scores did not differ by chemotherapy treatment exposure, and both groups improved significantly (P &lt; .01) in the year after primary treatment ended. However, adjuvant chemotherapy treatment was associated with significantly more severe physical symptoms, including musculoskeletal pain (P = .01), vaginal problems (P &lt; .01), weight problems (P = .01), and nausea (P = .03). Conclusion Physical and psychosocial functioning improved significantly after breast cancer treatment, independent of receipt of adjuvant chemotherapy. Women who received chemotherapy experienced more severe and persistent physical symptoms that should be more effectively managed as part of survivorship care.
THE RADIUM CLIMACTERIC
Authors: P. C. Fenwick
Journal: BMJ (1929)

T.N the menorrhagcia of middle life radium has proved of so mnuclh value that if miialignancy and fibroid disease are carefully excluded, radium can be safely recommended.In tllis department we have, duirinog the last four and a lalf-vears, tleated 89 patients suffering friom severe uterine haemiorrhage.The average age has been 47 years, and the average dturatioln of severe haemorrhage has been two years.Elach case lhas bee'n carefuly followed up every tlhr ee Thonths, anld our reports to date slhow that 73 patien-ts report quite free frnom symptoms, 2 have been lost sight of, onie failed to receive any benefit from the treatmen-t, anid 13 have been treated too recently to report.The one
Abstract 13745: Severity of Functional Mitral Regurgitation During Maximal Exercise Testing in Heart Failure: Additional Value of Combining Echocardiography with Cardiopulmonary Exercise Testing
Authors: Greta Generati, Francesco Bandera, Marta Pellegrino, Valentina Labate, Eleonora Alfonzetti, Marco Guazzi
Journal: Circulation (2014)

Background: In heart failure (HF) patients the severity of mitral regurgitation (MR) at rest has a well established prognostic value and its increase during exercise further adds to an increased risk. Our goal was to define the relationship between the degree of exercise MR severity with cardiopulmonary and echocardiographic related phenotypes in a cohort of HF patients. Methods: 71 HF reduced ejection fraction patients (mean age 67±11; male 72%; ischemic etiology 61%; NYHA class I, II, III and IV 13%, 36%, 39% and 12%, mean ejection fraction 33±9%) underwent cardiopulmonary exercise test (CPET) on tiltable cycle-ergometer combined with echocardiography at rest and during exercise. The population was divided into two groups according to the degree of functional peak MR: no to mild/moderate MR (no MR, MR1+ and MR2+) vs moderate/severe MR (MR3+ and MR4+). Results: A good correlation (ρ coefficient= 0.49) was found between the degree of dynamic MR and PASP at peak exercise. Despite similar echocardiographic profile at rest patients with significant peak MR (MR≥3+) had worse exercise performance (lower peak VO2, O2 pulse and workload) and impaired ventilatory efficiency (higher VE/VCO2 slope). Conclusions: In HF patients the severity of exercise-induced MR is associated with the most unfavorable performance and pulmonary hemodynamic response. A combined approach with CPET and echocardiographic assessment can help to early unmask and target functional MR and its related unfavorable phenotypes.
PROfusion?: Genetically Tagged Proteins for Functional Proteomics and Beyond
Authors: Brent L. Kreider
Journal: Medicinal Research Reviews (2000)

As a new enabling technology in functional genomics, Phylos, Inc. has pioneered PROfusiontrade mark technology, whereby proteins are covalently tagged with their own genetic information (mRNA). Using this technology, both synthetic and natural libraries (representing the repertoire of proteins naturally expressed in a given cell type or tissue source) have been constructed. Due to the in vitro nature of library construction, Phylos libraries are the largest described to date, up to 10(14) in size. From a library of such molecules, one can select for a protein function of choice with the benefit that the genetic material is linked to the protein for subsequent PCR amplification, enrichment, and, ultimately, identification.
Healthcare services for those with musculoskeletal conditions: a rheumatology service. Recommendations of the European Union of Medical Specialists Section of Rheumatology/European Board of Rheumatology 2006
Authors: A. D Woolf
Journal: Annals of the Rheumatic Diseases (2006)

Musculoskeletal conditions are very common across Europe. They affect all age groups, and the associated physical disability is an enormous burden on individuals and society. They can be effectively prevented and controlled in many situations, but this is not at present fully achieved. This report outlines what is required to achieve this and the role of rheumatology in providing these healthcare services. Strategies are given for the prevention and management of musculoskeletal conditions. The needs of people with these conditions are expressed in the PARE Manifesto and the clinical needs have been identified. The healthcare services required to implement these strategies and meet these needs are considered focusing on what services a rheumatology centre should provide. A key principle is that management of musculoskeletal conditions requires a coordinated, integrated, multidisciplinary and multiprofessional approach providing access to a combination of expertise and competencies. Guidance is given of what a rheumatology service should be expected to offer. For a rheumatology centre to provide these services, the need for appropriate facilities and resources is identified, which considers physical resources as well as personnel, training and management needs. Maintaining high standards of care and achieving the best outcomes at all times needs the monitoring of quality indicators as well as ongoing education and research. In conclusion, improving musculoskeletal health is dependent on access to effective treatments and this document shows how the services provided by a rheumatology centre is central to this.
Mechanisms underlying maintenance of smooth muscle cell quiescence in rat aorta: role of the cyclin dependent kinases and their inhibitors
Authors: T Izzard
Journal: Cardiovascular Research (2002)

Objective: We sought to understand why smooth muscle cell proliferation is effectively repressed in intact rat aortic tissue. Methods: Quiescent isolated rat aortic smooth muscle cells and segments of intact rat aorta were stimulated with 10% serum and the time course of expression and activity of proteins involved in cell cycle control were determined. Results: After serum stimulation, smooth muscle cells in intact aortic tissue exhibit no proliferation, whereas isolated cells entered S phase 14–16 h later. Activation of ERKs 1 and 2, and induction of cyclin D1 occurred both in isolated cells and aortic tissue. Regulation of Cdk4, cyclin E and Cdk2 protein levels was also not different. Levels of the cyclin-dependent kinase inhibitors (CKIs), p16 and p27, were initially high in quiescent isolated cells and tissue; levels were downregulated by serum in isolated cells but not in aortic tissue. Cyclin D1/Cdk4, and cyclin E/Cdk2 kinases were active before S phase entry in isolated cells, but remained inactive in aortic tissue. Conclusions: Cell cycle entry is prevented in aortic tissue, and this is associated with an inability to downregulate p16 and p27 CKIs, and therefore to activate cyclin D1 and cyclin E associated kinase activities.
Improving the acute medical take: the identification of hazardous alcohol consumption
Authors: A. J. Ball, D. Leaning, D. A. Elphick
Journal: Gut (2011)

<h3>Introduction</h3> Hazardous alcohol consumption is a growing public health problem. Recent NICE guidance suggests systematic identification of patients who misuse alcohol through the use of validated screening questionnaires such as the World Health Organisation developed AUDIT (Alcohol Use Disorders Identification Test) tool. Studies have shown brief targeted interventions in at risk groups to be cost effective in reducing readmission rates and the amount of alcohol consumed. We aimed to see how effectively patients drinking hazardous amounts of alcohol were being identified on our medical admissions unit and to compare AUDIT with the shorter FAST (Fast Alcohol Screening Tool). <h3>Methods</h3> A randomly selected cohort of medical patients was prospectively recruited on the day of their admission to Chesterfield Royal Hospital, between January 2010 and March 2010. Case note review for demographic data, documentation of alcohol history, MCV, gGT, and presenting complaint was performed. The AUDIT and FAST questionnaires were then performed with the patient. <h3>Results</h3> 188 patients (age range 17 – 100, median age 70) were included. AUDIT scores ranged 0–40. 156 (83%) had score £ 7; 21 (11%) had score 8–15 (hazardous); 4 (2%) had score 16–19 (harmful) and 7 (4%) had score<sup>3</sup> 20 (possible dependence). Only 1/32 patients with an alcohol score of &gt;7 had appropriate advice offered and documented according to their AUDIT score (8–15 brief advice, 16–19 extended brief advice, &gt;20 specialist referral offered). 13/68 (19%) patients with no documented alcohol history had an AUDIT score of &gt;7, 3 of whom had an AUDIT score of &gt;20. 2/61 patients with an. alcohol history documented as ‘no alcohol’ had an AUDIT score &gt;7. Chest pain was the most common (n = 7) presenting complaint for patients with an AUDIT score &gt;7, followed by shortness of breath (n = 4). gGT and MCV were poor predictors of hazardous alcohol consumption. The FAST questionnaire achieved 94% sensitivity and 100% specificity in detecting patients with hazardous alcohol consumption judged by the AUDIT score. Furthermore, FAST was considered easier and quicker to use. <h3>Conclusion</h3> Hazardous alcohol consumption is frequently under recognised, leading to missed opportunities for effective interventions that may reduce harm. Patients admitted with chest pain are not identified as being at high risk in the NICE guidance, but contain the highest number of hazardous drinkers in our study. Abbreviated questionnaires are accurate and easily used, and should be incorporated into an admission clerking of all presenting complaints.
Adjuvant Mitotane Treatment for Adrenocortical Carcinoma
Authors: Massimo Terzolo, Alberto Angeli, Martin Fassnacht, Fulvia Daffara, Libuse Tauchmanova, Pier Antonio Conton, Ruth Rossetto, Lisa Buci, Paola Sperone, Erika Grossrubatscher, Giuseppe Reimondo, Enrico Bollito, Mauro Papotti, Wolfgang Saeger, Stefanie Hahner, Ann-Cathrin Koschker, Emanuela Arvat, Bruno Ambrosi, Paola Loli, Gaetano Lombardi, Massimo Mannelli, Paolo Bruzzi, Franco Mantero, Bruno Allolio, Luigi Dogliotti, Alfredo Berruti
Journal: New England Journal of Medicine (2007)

Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence after radical resection. Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free survival.We performed a retrospective analysis involving 177 patients with adrenocortical cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005. Adjuvant mitotane was administered to 47 Italian patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German patients (control groups 1 and 2, respectively) did not receive adjuvant treatment after surgery.Baseline features in the mitotane group and the control group from Italy were similar; the German patients were significantly older (P=0.03) and had more stage I or II adrenocortical carcinomas (P=0.02) than did patients in the mitotane group. Recurrence-free survival was significantly prolonged in the mitotane group, as compared with the two control groups (median recurrence-free survival, 42 months, as compared with 10 months in control group 1 and 25 months in control group 2). Hazard ratios for recurrence were 2.91 (95% confidence interval [CI], 1.77 to 4.78; P<0.001) and 1.97 (95% CI, 1.21 to 3.20; P=0.005), respectively. Multivariate analysis indicated that mitotane treatment had a significant advantage for recurrence-free survival. Adverse events associated with mitotane were mainly of grade 1 or 2, but temporary dose reduction was needed in 13% of patients.Adjuvant mitotane may prolong recurrence-free survival in patients with radically resected adrenocortical carcinoma.
Antipsychotics-Containing Regimen As an Alternative to Standard Antiemetics for Delayed Nausea Induced by Highly Emetogenic Chemotherapy
Authors: Hiroshi Ishiguro, Kosuke Kawaguchi, Tomomi Nishimura, Masakazu Toi
Journal: Journal of Clinical Oncology (2013)

double-blind randomized clinical trial to determine the efficacy of the addition of dexamethasone on days 2 and 3, a secondgeneration 5-hydroxytryptamine receptor antagonist (5-HT RA; palonosetron), and a neurokinin-1-receptor antagonist (aprepitant) for delayed nausea. This study failed to show the benefit of palonosetron and aprepitant compared with a standard regimen that included prochlorperazine. The authors commented that most randomized trials reporting the efficacy of aprepitant did not use effective alternative medication, such as prochlorperazine, for delayednausea.Amongthe5-HTRAs,theeffectsofpalonosetronand granisetron for controlling delayed nausea are similar, provided that prochlorperazineisused. 1 Prochlorperazine,anantipsychotic,actson