tbuckley/cabot-search huggingface dataset:
Reframing the Ethical Issues in Part-Human Animal Research: The Unbearable Ontology of Inexorable Moral Confusion
Authors: Matthew H. Haber, Bryan Benham
Journal: The American Journal of Bioethics (2012)

Research that involves the creation of animals with human-derived parts opens the door to potentially valuable scientific and therapeutic advances, yet invokes unsettling moral questions. Critics and champions alike stand to gain from clear identification and careful consideration of the strongest ethical objections to this research. A prevailing objection argues that crossing the human/nonhuman species boundary introduces inexorable moral confusion (IMC) that warrants a restriction to this research on precautionary grounds. Though this objection may capture the intuitions of many who find this research unsettling, it relies on mistaken views of both biology and moral standing, ultimately distorting the morally relevant facts. We critically examine IMC, identify mistaken essentialist assumptions, and reframe ethical concerns. The upshot is a stronger line of objection that encourages a more inclusive and productive ethical discourse.
Pyridoxine and Levodopa in The Treatment of Parkinsonism
Authors: Melvin D. Yahr
Journal: JAMA (1972)

<h3>To the Editor.—</h3> In his letter appearing in the February 28th, 1972 issue ofThe Journal,<sup>1</sup>Dr. van Woert rightfully calls attention to the potential hazard of dietary restriction of pyridoxine hydrochloride during levodopa therapy for parkinsonism. It is indeed regrettable that some physicians and pharmaceutical companies have seen fit to recommend such dietary advice without evidence that this is a desirable, let alone a safe thing to do. In our original report<sup>2</sup>describing the reduction of the therapeutic effectiveness of levodopa when pyridoxine is administered concomitantly, we were careful to point out that this only occurred with daily supplemental doses of the order of 10 to 25 mg and on some occasions 5 mg. No evidence was found, nor did we imply that the amount of pyridoxine contained in the standard daily diet, estimated to be less than 1 mg a day, would interfere with the therapeutic
Dynamics of the background outward current of single guinea pig ventricular myocytes. Ionic mechanisms of hysteresis in cardiac cells.
Authors: M Delmar, J Ibarra, J Davidenko, P Lorente, J Jalife
Journal: Circulation Research (1991)

Subthreshold potentials are thought to be mediated by time-independent, "passive" background currents. In this study, we show that the background current-voltage (I-V) relation of guinea pig ventricular myocytes is changed significantly by repetitive stimulation, in such a way that cell excitability becomes enhanced. Myocytes were used for whole-cell voltage-clamp experiments. A voltage-clamp ramp (100 mV/sec) to -50 mV was applied from a holding potential of -100 mV. Subsequently, a train of square voltage-clamp pulses to +10 mV (duration, 300 msec; interpulse interval, 300 msec) was delivered from a holding potential of -85 mV. A new ramp was applied again immediately after the train, and the resulting I-V curve was compared with that obtained before the train. Pulsing displaced the I-V relation to the right, the zero-current point becoming 1-2 mV less negative, and increased the degree of inward-going rectification. These changes were insensitive to tetrodotoxin (30 microM); disappeared during superfusion with cobalt (2 mM), verapamil (22 microM), or ryanodine (5 microM); and could not be mimicked by agonists of the protein kinase C system. In the presence of cesium (8 mM), pulsing still displaced the I-V curve to the right. However, the linear portion of the curve became steeper after the train. Subtraction of the cesium-sensitive current from control revealed that, although the zero-current point remained constant, the I-V relation showed a stronger inward-going rectification after pulsing. In accordance with these results, we have demonstrated hysteresis of excitability in ventricular myocytes. We conclude that the observed changes are mediated by an increase in intracellular calcium, which leads to an increase in rectification of IK1, as well as to activation of another membrane-conductance system, perhaps the Na-Ca exchange or the Ca(2+)-activated, nonselective current.
Myocardial perfusion-contraction matching. Implications for coronary heart disease and hibernation.
Authors: J Ross
Journal: Circulation (1991)

Experimental studies demonstrate that short-term regional perfusion-contraction matching, in which the energy demands of regional myocardial contraction are reduced to match the diminished myocardial substrate supply, occurs during states of low coronary blood flow under resting conditions and during exercise-induced ischemia. This phenomenon is rapidly reversible and appears to occur in several clinical settings. Sustained perfusion-contraction matching is observed in states of partial experimental ischemia of intermediate duration lasting several hours. This condition might be called short-term hibernation and resembles clinical conditions such as unstable angina pectoris or myocardial infarction with some residual perfusion in which the contractile defect can be improved by reperfusion provided the ischemia is not severe enough to cause transmural necrosis. Such experimental and clinical observations may or may not relate to the setting of regional dysfunction at rest in patients with chronic coronary heart disease, in whom manifestations of acute ischemia may be absent but improvement of wall motion abnormalities occurs after CABG or balloon angioplasty. This condition may constitute the hypothetical state of chronic myocardial hibernation, for which tentative evidence exists from metabolic and perfusion studies using PET. Whether such a condition of prolonged perfusion-contraction matching might be associated with adaptive processes that could allow its persistence for long periods without manifest ischemia remains to be investigated.
Learning to Empower Patients: Results of Professional Education Program for Diabetes Educators
Authors: Robert M Anderson, Martha M Funnell, Patricia A Barr, Robert F Dedrick, Wayne K Davis
Journal: Diabetes Care (1991)

The patient empowerment approach to diabetes education is intended to enable patients to make informed decisions about their own diabetes care and to be fully responsible members of the health-care team. Facilitating patient empowerment requires a specific set of skills and attitudes on the part of diabetes educators. A professional education program designed to facilitate the acquisition and enhancement of the requisite skills and attitudes was designed, implemented, and evaluated. The program involved adhering to a simulated diabetes care regimen for 3 days followed by a 3-day intensive skills-based workshop. The 23 educators who participated in the first two offerings of this program made significant gains in their counseling skills and demonstrated a positive change in attitude.
Change in portal flow after liver transplantation: Effect on hepatic arterial resistance indices and role of spleen size
Authors: Massimo Bolognesi, David Sacerdoti, Giancarlo Bombonato, Carlo Merkel, Giovanni Sartori, Roberto Merenda, Valeria Nava, Paolo Angeli, Paolo Feltracco, Angelo Gatta
Journal: Hepatology (2002)

Information on changes in splanchnic hemodynamics after liver transplantation is incomplete. In particular, data on long-term changes are lacking, and the relationship between changes in arterial and portal parameters is still under debate. The effect of liver transplantation on splanchnic hemodynamics was analyzed with echo-Doppler in 41 patients with cirrhosis who were followed for up to 4 years. Doppler parameters were also evaluated in 7 patients transplanted for acute liver failure and in 35 controls. In cirrhotics, portal blood velocity and flow increased immediately after transplantation (from 9.1 ± 3.7 cm/sec to 38.3 ± 14.6 and from 808 ± 479 mL/min to 2,817 ± 1,153, respectively, P &lt; .001). Hepatic arterial resistance index (pulsatility index) also augmented (from 1.36 ± 0.32 to 2.34 ± 1.29, P &lt; .001) and was correlated with portal blood velocity and flow. The early changes in these parameters were related, in agreement with the hepatic buffer response theory. Portal flow returned to normal values after 2 years. Superior mesenteric artery flow normalized after 3 to 6 months. Splenomegaly persisted after 4 years, when spleen size was related to portal blood flow. In 7 patients transplanted for acute liver failure, portal flow, and hepatic arterial resistance index were normal after transplantation. In conclusion, a high portal flow was present in cirrhotics until 2 years after transplantation, probably because of maintenance of elevated splenic flow. An early increase in hepatic arterial resistance indices is a common finding, but it is transient and is related to the increase in portal blood flow. A normal time course of portal-hepatic hemodynamics was detected in patients transplanted for acute liver failure.
Insulin Underdelivery From Implanted Pumps Using Peritoneal Route: Determinant role of insulin pump compatibility
Authors: Eric Renard, Serge Bouteleau, Dominique Jacques-Apostol, Dominique Lauton, Françoise Gibert-Boulet, Guy Costalat, Jacques Bringer, Claude Jaffiol
Journal: Diabetes Care (1996)

OBJECTIVE To evaluate the incidence and investigate determinants of insulin underdelivery events occurring with implanted pumps using peritoneal route from a 103 patient-year experiment. RESEARCH DESIGN AND METHODS Of the MiniMed (MIP 2001) pumps implanted in 47 type I diabetic patients, 70 were refilled quarterly with four successive batches (A, B, C, D) of U400 Hoechst 21 PH neutral insulin during a 3-year study period. Any reduction of insulin flow rate &amp;gt;15% was considered as abnormal insulin delivery. Diagnosis of the cause of underdelivery was established according to the response to the following steps: 1) 0.01 mol/l NaOH rinse of pump circuits to solubilize insulin aggregates, 2) surgical examination and replacement of blocked catheters, and 3) postsurgical 0.01 mol/l NaOH rinse of pump. Step 2 was selected first if the increase of insulin requirements or reduction of flow rate were &amp;gt; 50%. Relative contributions of insulin and the implanted system to underdelivery events were analyzed. RESULTS There were 76 episodes of insulin underdelivery that occurred during the study, resulting in an incidence of 74 events per 100 patient-years. Of 52 NaOH pump rinses, 30 restored normal flow rate. Surgery, performed after rinse failure (n = 22) or as the first step (n = 24), disclosed catheter blockages due to tip obstructions in 28 cases and omental encapsulations in 18 other cases. Five combined severe reductions of pump flow rate requiring pump replacements were diagnosed during surgery, and additional NaOH rinses had to be performed after catheter change in 12 other cases. Analysis of the incidence of underdelivery events indicated that both pump- and catheter-related problems were significantly increased while implanted systems infused batches B, C, and D versus batch A (P &amp;lt; 0.01), whereas the duration of pump implantation had no significant influence. CONCLUSIONS Underdelivery events constitute serious limiting obstacles to prolonged peritoneal insulin infusion from implanted pumps. Progress in insulin pump compatibility is expected to reduce their occurrence and, thus, to improve the feasibility of this treatment.
Extrinsic allergic alveolitis caused by a cold water humidifier.
Authors: A S Robertson, P S Burge, G A Wieland, M H Carmalt
Journal: Thorax (1987)

Three workers developed classical extrinsic allergic alveolitis while working in a printing works that had a contaminated cold water humidifier. All had nodular shadows on their chest radiographs, reduced gas transfer measurements, and lung biopsy specimens that showed an alveolitis with giant cells and cholesterol clefts. In two subjects bronchoalveolar lavage was performed and the lavage fluid contained more than 70% lymphocytes in each case. Bronchial provocation tests with the humidifier antigen in these two workers reproduced their symptoms. Unlike previously reported cases, where exposure was to humidifiers working at generally higher temperatures, challenge with thermophilic actinomycetes in our two patients produced no reaction. Tests for precipitins to the humidifier antigen gave strongly positive reactions in the three workers but no single organism isolated from the humidifier produced a significantly positive reaction.
The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4+ T cells
Authors: Samuel Bertin, Yukari Aoki-Nonaka, Petrus Rudolf de Jong, Lilian L Nohara, Hongjian Xu, Shawna R Stanwood, Sonal Srikanth, Jihyung Lee, Keith To, Lior Abramson, Timothy Yu, Tiffany Han, Ranim Touma, Xiangli Li, José M González-Navajas, Scott Herdman, Maripat Corr, Guo Fu, Hui Dong, Yousang Gwack, Alessandra Franco, Wilfred A Jefferies, Eyal Raz
Journal: Nature Immunology (2014)
Getting scientists together: the ACR/EULAR exchange programme
Authors: D Elewaut
Journal: Annals of the Rheumatic Diseases (2003)

Many of the landmark discoveries in biomedical science were based on individual brilliance and talent. However, over the years it became apparent that the pathogenesis of various diseases, and of autoimmune disorders in particular, is complex and requires a multidisciplinary approach. For example, the search for disease susceptibility genes in human diseases demands intensive collaboration between clinicians, geneticists, molecular biologists, and biostatisticians. Furthermore, the technological revolution in the field of biomedical research requires international collaboration to exchange the necessary expertise. International meetings, although very useful for the scientific community, have their limitations. By their nature, such meetings can increase subspecialisation and in overview sessions the large numbers of participants may be counterproductive for personal contact. This can be a particular barrier to younger members of the scientific community who wish to get involved with other groups. However, it will fall to these young scientists to strengthen the network to target diseases.

Despite many similarities among scientific groups on either side, the Atlantic Ocean has proved to be a major barrier to such effort. Meeting the demand for a forum for young rheumatologists, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) established an exchange programme in 1997 between European and American scientists in the field of rheumatology. The first exchange took place in 1998. Since then each year, three junior academic scientists accompanied by one senior rheumatologist of ACR and EULAR, respectively, travel across the ocean to visit academic centres for a …
Traumatic Rupture of the Pancreas
Authors: W. Burnett
Journal: BMJ (1955)

experience suggests that this type of acute anxiety reaction tends to occur more often during hypnography than in verbal hypnoanalysis.An inadequate, dependent young man was receiving treatment for loss of confidence.Whlen hypnotized he was given a crayon and told that his hand would draw something that represented his problems.With a rhythmical movement he made a series of marks on the paper.He became more and more preoccupied with what he was doing.The rhythmical character of the move- ment became more pronounced.His expression was very intense, and it seemed obvious that the drawing was a sexual equivalent.He begani to verbalize his thoughts, and the sexual nature of the activity was confirned.He abreacted a good deal of emotion.Hypnosis became lighter.He suddenly turned very pale and started to sweat.He woke from hypnosis spontaneously.In a shaky voice he said that lhe thought he had woken up and thought he was going to vomit.He became intensely tremulous; the sweating was profuse; his pulse was rapid and of poor volume.He looked alarmingly ill.He was immediately rehypnotized and given suggestions of calm and well-being.His physical condition was restored in ten to fifteen minutes.In subsequent sessions care was taken to maintain an adequate depth of hypnosis, and no further complications were encountered.
Effects of Methyldopa in Hypertension
Authors: Max Charles Igloe
Journal: JAMA (1964)

Methyldopa demonstrated antihypertensive activity when prescribed in initial amounts of 1 gm daily in four divided doses to 51 patients with mild to moderate hypertension. The mean arterial pressure was reduced by an average of 34/18 mm Hg in the supine position and 34/24 mm Hg in the standing position. While methyldopa did not alter the hemogram, urinalysis, or liver-function pattern, febrile reactions and occipital headaches were outstanding side reactions. Other side effects included drowsiness and dry mouth, which were frequent but transient and tolerable.
What does radiotherapy add to survival over endoscopic intubation alone in inoperable squamous cell oesophageal cancer?
Authors: S E Oliver, C S Robertson, R F Logan, M Sokal, J C Pearson, M Atkinson
Journal: Gut (1990)

<h3>Introduction</h3> The Australian Council on Healthcare Standards (ACHS) set criteria for the delivery of healthcare services in Australia. While a voluntary process, continual accreditation with ACHS is an expectation of, and for, Australian healthcare providers. Juxtapositioned with the ACHS, the Nursing and Midwifery Board of Australia (NMBA) set the mandatory practice requirements of, and for, Australian nurses. Despite these overarching quality and governance directives, a regional Queensland Hospital and Health Service (HHS) demonstrated deficits in the quality of nursing care. Accordingly, a HHS project was commissioned with the aim of producing a quantum shift in the quality of nursing services such that the service was <i>ready-everyday</i> for accreditation assessment, and nursing practice exemplified the NMBA standards. Several barriers to achieving the aim were identified and it was considered that the implementation of critical system changes would structurally and operationally support the achievement of the aim. The system changes are pivoted around an interactive matrix that links nursing care services to the array of nursing professional and practice standards and provides real-time quantitative output measures. This paper outlines the protocol that will be used to establish, implement and evaluate the matrix. <h3>Methods and analysis</h3> A participatory action research design with a modified Delphi methodology will be used for the development the matrix. The organisational change management around the matrix implementation will be informed by Kotter’s model and supported by the use of the McKinsey 7S. The matrix implementation phase will be conducted using a modified <i>Promoting Action on Research Implementation in Health Services</i> model. Quantitative and qualitative data will be collected over a 12 month pre-test/post-test design to measure the statistical significance of the matrix in supporting compliance with nursing standards and the achievement of quality nursing care. Quantitative data from quality of care assessments will be analysed using descriptive and comparative statistics. Qualitative data from staff surveys will be analysed by content analysis of the major themes (n~200). <h3>Ethics and dissemination</h3> The project has ethics approval from a Queensland Health Human Research Ethics Committee. Results will be reported to participants and other stakeholders at seminars and conferences and through peer-reviewed publications.
Non-steroidal anti-inflammatory drugs and benign oesophageal stricture.
Authors: S R Heller, I W Fellows, A L Ogilvie, M Atkinson
Journal: BMJ (1982)

Drug histories were obtained from 76 patients at the time of initial Eder-Puestow dilatation for benign oesophageal stricture. Six patients had consumed drugs known to cause oesophageal ulceration (emepronium bromide and potassium preparations). Of the remaining 70 patients, 22 had regularly taken a non-steroidal anti-inflammatory drug before the onset of dysphagia compared with 10 patients in a control group matched for age and sex; this difference was significant (p less than 0.02). Non-steroidal anti-inflammatory drugs may have a causative role in the formation of oesophageal stricture in patients with gastro-oesophageal reflux, in whom they should be prescribed with caution.
DNA Polymerase ζ Accounts for the Reduced Cytotoxicity and Enhanced Mutagenicity of Cisplatin in Human Colon Carcinoma Cells That Have Lost DNA Mismatch Repair
Authors: Xinjian Lin, Julie Trang, Tsuyoshi Okuda, Stephen B. Howell
Journal: Clinical Cancer Research (2006)

Abstract The mutagenicity of cis-diamminedichloroplatinum(II) (DDP; cisplatin) and the rate at which resistance develops with repeated exposure to DDP are dependent on mutagenic translesional replication across DDP DNA adducts, mediated in part by DNA polymerase ζ, and on the integrity of the DNA mismatch repair (MMR) system. The aim of this study was to determine whether disabling Pol ζ by suppressing expression of its hREV3 subunit in human cancer cells can reduce the mutagenicity of DDP and whether loss of MMR facilitates mutagenic Pol ζ-dependent translesional bypass. The HCT116+ch3 (MMR+/REV3+) and HCT116 (MMR−/REV3+) human colon carcinoma cell lines were engineered to suppress hREV3 mRNA by stable expression of a short hairpin interfering RNA targeted to hREV3. The effect of knocking down REV3 expression was to completely offset the DDP resistance mediated by loss of MMR. Knockdown of REV3 also reduced the mutagenicity of DDP and eliminated the enhanced mutagenicity of DDP observed in the MMR−/REV3+ cells. Similar results were obtained when the ability of the cells to express luciferase from a platinated plasmid was measured. We conclude that Pol ζ plays a central role in the mutagenic bypass of DDP adducts and that the DDP resistance, enhanced mutagenicity, and the increased capacity of MMR−/REV3+ cells to express a gene burdened by DDP adducts are all dependent on the Pol ζ pathway.
GMC guidelines will double ENT consultation times
Authors: R. Dobson
Journal: BMJ (2002)

Keeping to the General Medical Council's current guidelines on good medical practice would more than double the length of individual consultation times in ear, nose, and throat outpatient clinics. This is the finding of a new study, whose authors suggest that it may be impossible to meet these demands and others without doubling staffing levels.

The results of the study, which looked at the impact that the guidelines would have on otolaryngology outpatient consultations, are reported in Clinical Otolaryngology (2002;335-7).

The report says that the GMC, in its booklets Good Medical Practice and Seeking Patients' Consent: The Ethical Considerations , has set out what should be discussed with a patient during a consultation before obtaining consent. In their study, the authors compared the length of a usual outpatient consultation with the length of a “good practice” consultation for …
Chewing the Fat
Authors: Walter Willett, Frank M. Sacks
Journal: New England Journal of Medicine (1991)

IN this issue of the Journal, Small et al.1 provide instructions for reducing the cholesterol content of red meat and partially replacing its natural fat with vegetable fat. This delightful lesson in food composition appears against a background of recent Journal articles relating various types and amounts of dietary fat to levels of blood lipids.2 3 4 5 Ultimately, we must put these and other pieces of data together to derive a rational guide to eating. What are appropriate goals regarding the amount and type of fat in our diets?A consideration of the criteria for setting dietary goals or recommendations may . . .