tbuckley/cabot-search huggingface dataset:
Duties of a Doctor as a Citizen
Authors: E. C. Dawson
Journal: BMJ (1954)

The concept of the preservation of secrecy between doctor and patient is something that is accepted as a matter of course and is a basic factor in the doctor patient relationship. The concept dates back to the teachings of Hippocrates, and is as much alive to-day in the minds both of doctors and of patients as ever before, even in the face of the massive interchange of confiden tial medical information that passes to and fro in the Welfare State. In the course of his work the doctor daily learns from his patients much of their personal contacts and dealings with other people which help to build up the environment of their existence and about which he is often able to give helpful advice. The occasion may arise when the patient's relationship with others may be such as to expose them to harm or danger. The duty of the doctor in such a case is to con demn the relationship and to use all his power to per suade the patient from taking any steps likely to harm other people. Such action on the doctor's 'art is usually successful. The patient, however, may stubbornly refuse to follow this advice, and he makes it quite clear that, in order to soften his own position, he intends to harden it for others to the extent of committing fraud or crime or of endangering life or health. The ordinary citizen placed in such a position would have a clear duty to take steps to prevent the commission of crime or to see that the offender was apprehended for punishment or the prevention of further crime. The doctor who learns of the circumstances through professional relationship is under an obligation of secrecy to remain silent, yet his moral inclinations and duty as a citizen urge him to do all in his power to prevent harm to others. His duty as a doctor is in direct conflict with his duty as a citizen. The object of this paper is to examine the teachings of authority, the position in law, and the moral aspects involved in such circumstances and to analyse the replies to four specific questions bearing on the subject from representative groups of doctors and laymen.
Analysis of components in a cardiogenic hypertensive chemoreflex.
Authors: T N James, J H Isobe, F Urthaler
Journal: Circulation (1975)

A cardiogenic hypertensive chemoreflex was studied in 38 anesthetized and three unanesthetized dogs. Serotonin (100 mug/ml) injected into either the left atrium or small brancehes of the proximal left coronary artery produced a maximal response, with 96 +/- 18 mm Hg increment in mean aortic pressure within 6 +/- 2 seconds, lasting about 1 min; a later phase of the same hypertension lasted 9 +/- 5 minutes more and could partially be produced with serotonin injected into the thoracic aorta. Injections into the distal left coronary artery produced only the Bezold-Jarisch reflex. Concomitant with the immediate hypertension there were vagal and sympathetic efferent effects in both the sinus node and the atrioventricular (A-V) junction. Either of these effects could be selectively eliminated and the other augmented by direct local perfusion with an appropriate cholinergic (atropine 10 mug/ml) or adrenergic beta-receptor (propranolol 10 mug/ml) blocking agent. Bilateral vagotomy markedly attenuated but did not eliminate the acute hypertension, but it abolished both chronotropic and dromotropic effects. Phentolamine (2 mg/min i.v.) markedly diminished the hypertensive response. Guanethidine or reserpine pretreatment markedly diminished the hypertensive response; reserpine eliminated the electrophsiologic effects but guanethidine did not. Infiltration of serotonin around the main left coronary partially reproduced the reflex, but similar infiltration of xylocaine hydrochloride blocked the reflex. Serial section histologic studies of the region around the main left coronary atery in seven dog hearts and nine human hearts demonstrated the presence of a small structure resembling a chemoreceptor; its blood supply originated from the left coronary artery. Some possible clinical implications are discussed.
Therapies with Diverse Mechanisms of Action Kill Cells by a Similar Exponential Process in Advanced Cancers
Authors: Krastan B. Blagoev, Julia Wilkerson, Wilfred D. Stein, James Yang, Susan E. Bates, Tito Fojo
Journal: Cancer Research (2014)

Abstract Successful cancer treatments are generally defined as those that decrease tumor quantity. In many cases, this decrease occurs exponentially, with deviations from a strict exponential being attributed to a growing fraction of drug-resistant cells. Deviations from an exponential decrease in tumor quantity can also be expected if drugs have a nonuniform spatial distribution inside the tumor, for example, because of interstitial pressure inside the tumor. Here, we examine theoretically different models of cell killing and analyze data from clinical trials based on these models. We show that the best description of clinical outcomes is by first-order kinetics with exponential decrease of tumor quantity. We analyzed the total tumor quantity in a diverse group of clinical trials with various cancers during the administration of different classes of anticancer agents and in all cases observed that the models that best fit the data describe the decrease of the sensitive tumor fraction exponentially. The exponential decrease suggests that all drug-sensitive cancer cells have a single rate-limiting step on the path to cell death. If there are intermediate steps in the path to cell death, they are not rate limiting in the observational time scale utilized in clinical trials—tumor restaging at 6- to 8-week intervals. On shorter time scales, there might be intermediate steps, but the rate-limiting step is the same. Our analysis, thus, points to a common pathway to cell death for cancer cells in patients. See all articles in this Cancer Research section, “Physics in Cancer Research.” Cancer Res; 74(17); 4653–62. ©2014 AACR.
ST. GEORGE'S HOSPITAL: TRACHEITIS: TRACHEOTOMY: DEATH TWENTY-EIGHT HOURS AFTER THE OPERATION
Authors: J. A. Wilson
Journal: BMJ (1856)

to the HospitlL '2.D., aged 4j, the youngest of eight children, was admitted on November 2nd, at 6 P.m., suffering from croup.Ee had not been quite -well since an attack of scarlatina six weeks before.The mother stated that, when any of her uhildren had colds or coughs, they were mbinvaibly troubled -with more hoarseness and croupy respiration than usually attends these complaints.On October 31st, the child sat for.along tine in a cart at the door, and caught cold; but it-was not until 11 X.x. that his mother heard him cough.He slept well, and went out to play'the following morning.At dinner he did not eat heartily as usual; and about
Urologic Aspects of Radical Pelvic Surgery
Authors: Langdon Parsons, Wyland F. Leadbetter
Journal: New England Journal of Medicine (1950)

IN JULY, 1948, Brunschwig1 reported his experience with ultraradical surgery for advanced pelvic carcinoma. Since that time considerable interest has been created in the radical surgical treatment of malignant lesions of the pelvic viscera previously regarded as beyond the scope of effective treatment.Our own series began in December, 1947, on material available from the tumor clinics of the Massachusetts General, Palmer Memorial and Pondville hospitals. The program was undertaken in an attempt to find out whether this type of surgery had anything to offer, whether the patients could survive the operation, whether the patients so treated could live happy, . . .
Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigenetic regulation
Authors: C.‐H. Kuo, C.‐C. Hsieh, H.‐F. Kuo, M.‐Y. Huang, S.‐N. Yang, L.‐C. Chen, S.‐K. Huang, C.‐H. Hung
Journal: Allergy (2013)

Abstract Background Exposure to environmental endocrine‐disrupting chemicals ( EDC s) is associated with allergy, chronic inflammation, and immunodeficiency. Phthalates, the common EDC s used in plastic industry, may act as adjuvants to disrupt immune system and enhance allergy. Plasmacytoid DC s ( pDC s) are predominant cells secreting type I interferon ( IFN ) against infection and are professional antigen‐presenting cells in regulating adaptive immunity. However, the effects of phthalates on the function of pDC s are unknown. Methods Circulating pDC s were isolated from healthy subjects, were pretreated with diethylhexyl phthalate ( DEHP ) and butyl benzyl phthalate ( BBP ), and were stimulated with T oll‐like receptor ( TLR )‐9 agonist C p G . IFN ‐α/ IFN ‐β levels, surface markers, and T ‐cell stimulatory function were investigated using ELISA , flow cytometry, and pDC / T ‐cell coculture assay. Mechanisms were investigated using receptor antagonists, pathway inhibitors, Western blotting, and chromatin immunoprecipitation. Results Diethylhexyl phthalate and butyl benzyl phthalate suppressed C p G ‐induced IFN ‐α/ IFN ‐β expression in pDC s, and the effect was reversed by aryl hydrocarbon receptor ( AHR ) antagonist. Diethylhexyl phthalate suppressed C p G ‐activated mitogen‐activated protein kinase ( MAPK )‐ MEK 1/2‐ ERK ‐ ELK 1 and NF κ B signaling pathways. Diethylhexyl phthalate suppressed C p G ‐induced interferon regulatory factor ( IRF )‐7 expression by suppressing histone H 3 K 4 trimethylation at IRF 7 gene promoter region through inhibiting translocation of H 3 K 4‐specific trimethyltransferase WDR 5 from cytoplasm into nucleus. Butyl benzyl phthalate or diethylhexyl phthalate‐treated pDC s suppressed IFN ‐γ but enhanced IL‐13 production by CD 4+ T cells. Conclusion Phthalates may interfere with immunity against infection and promote the deviation of T h2 response to increase allergy by acting on human pDC s via suppressing IFN ‐α/ IFN ‐β expression and modulating the ability to stimulate T ‐cell responses.
Synaptotagmin II Negatively Regulates Ca2+-triggered Exocytosis of Lysosomes in Mast Cells
Authors: Dana Baram, Roberto Adachi, Ora Medalia, Michael Tuvim, Burton F. Dickey, Yoseph A. Mekori, Ronit Sagi-Eisenberg
Journal: The Journal of Experimental Medicine (1999)

Synaptotagmins (Syts) I and II are believed to act as Ca2+ sensors in the control of neurotransmission. Here we demonstrate that mast cells express Syt II in their lysosomal fraction. We further show that activation of mast cells by either aggregation of FcεRI or by Ca2+ ionophores results in exocytosis of lysosomes, in addition to the well documented exocytosis of their secretory granules. Syt II directly regulates lysosomal exocytosis, whereby overexpression of Syt II inhibited Ca2+-triggered release of the lysosomal processed form of cathepsin D, whereas suppression of Syt II expression markedly potentiated this release. These findings provide evidence for a novel function of Syt II in negatively regulating Ca2+-triggered exocytosis of lysosomes, and suggest that Syt II–regulated secretion from lysosomes may play an important role in mast cell biology.
Amino acid metabolism in exercising man
Authors: Philip Felig, John Wahren
Journal: Journal of Clinical Investigation (1971)

Arterial concentration and net exchange across the leg and splanchnic bed of 19 amino acids were determined in healthy, postabsorptive subjects in the resting state and after 10 and 40 min of exercise on a bicycle ergometer at work intensities of 400, 800, and 1200 kg-m/min. Arterio-portal venous differences were measured in five subjects undergoing elective cholecystectomy.
Enterogastrone-like effect of peptide YY is vagally mediated in the dog.
Authors: T N Pappas, H T Debas, I L Taylor
Journal: Journal of Clinical Investigation (1986)

Intraluminal fat inhibits gastric secretion through as yet undetermined mechanisms which involve release of one or more hormonal enterogastrones. As intraluminal fat releases Peptide YY (PYY) in amounts sufficient to inhibit meal-stimulated acid secretion, this ileo-colonic peptide exhibits the characteristics required of an enterogastrone. The present study seeks to determine the mechanism by which PYY inhibits acid secretion by examining the effects of PYY on gastric acid stimulated by pentagastrin, histamine, and bethanechol. In addition, effects of PYY on the acid response to sham feeding and distention of a denervated gastric pouch were examined. A dose of PYY (400 pmol X kg-1 X h-1) was employed that reproduced blood levels observed after intestinal perfusion with oleic acid and inhibited the acid secretory response to an intragastric meal by 35 +/- 6%. This same dose of PYY maximally inhibited histamine- and pentagastrin-stimulated acid secretion by 28 +/- 7% (P less than 0.05), and 17 +/- 4% (P less than 0.05), respectively. Although PYY had no effect on bethanechol-stimulated secretion it markedly inhibited the secretory response to sham feeding, maximally reducing secretion by 90 +/- 4% (P less than 0.01). We speculate that PYY acts by inhibiting acetylcholine release from vagal nerve fibers rather than by inhibiting acetylcholine's action on the parietal cell. The demonstration that PYY virtually abolishes cephalic phase acid secretion while having little if any effect on the response to exogenous secretogogues gives PYY unique characteristics among the known hormonal inhibitors of gastric secretion.
The Lifetime Cost of Diabetes and Its Implications for Diabetes Prevention
Authors: Xiaohui Zhuo, Ping Zhang, Lawrence Barker, Ann Albright, Theodore J. Thompson, Edward Gregg
Journal: Diabetes Care (2014)

To assess the cost implications of diabetes prevention, it is important to know the lifetime medical cost of people with diabetes relative to those without. We derived such estimates using data representative of the U.S. national population.We aggregated annual medical expenditures from the age of diabetes diagnosis to death to determine lifetime medical expenditure. Annual medical expenditures were estimated by sex, age at diagnosis, and diabetes duration using data from 2006-2009 Medical Expenditure Panel Surveys, which were linked to data from 2005-2008 National Health Interview Surveys. We combined survival data from published studies with the estimated annual expenditures to calculate lifetime spending. We then compared lifetime spending for people with diabetes with that for those without diabetes. Future spending was discounted at 3% annually.The discounted excess lifetime medical spending for people with diabetes was $124,600 ($211,400 if not discounted), $91,200 ($135,600), $53,800 ($70,200), and $35,900 ($43,900) when diagnosed with diabetes at ages 40, 50, 60, and 65 years, respectively. Younger age at diagnosis and female sex were associated with higher levels of lifetime excess medical spending attributed to diabetes.Having diabetes is associated with substantially higher lifetime medical expenditures despite being associated with reduced life expectancy. If prevention costs can be kept sufficiently low, diabetes prevention may lead to a reduction in long-term medical costs.
MicroRNA Expression in Response to Controlled Exposure to Diesel Exhaust: Attenuation by the Antioxidant <i>N</i> -Acetylcysteine in a Randomized Crossover Study
Authors: Masatsugu Yamamoto, Amrit Singh, Francesco Sava, Mandy Pui, Scott J. Tebbutt, Christopher Carlsten
Journal: Environmental Health Perspectives (2013)

Adverse health effects associated with diesel exhaust (DE) are thought to be mediated in part by oxidative stress, but the detailed mechanisms are largely unknown. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and may respond to exposures such as DE.We profiled peripheral blood cellular miRNAs in participants with mild asthma who were exposed to controlled DE with and without antioxidant supplementation.Thirteen participants with asthma underwent controlled inhalation of filtered air and DE in a double-blinded, randomized crossover study of three conditions: a) DE plus placebo (DEP), b) filtered air plus placebo (FAP), or c) DE with N-acetylcysteine supplementation (DEN). Total cellular RNA was extracted from blood drawn before exposure and 6 hr after exposure for miRNA profiling by the NanoString nCounter assay. MiRNAs significantly associated with DEP exposure and a predicted target [nuclear factor (erythroid-derived 2)-like 2 (NRF2)] as well as antioxidant enzyme genes were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for validation, and we also assessed the ability of N-acetylcysteine supplementation to block the effect of DE on these specific miRNAs. 8-hydroxy-2'-deoxyguanosine (8-OHdG) was measured in plasma as a systemic oxidative stress marker.Expression of miR-21, miR-30e, miR-215, and miR-144 was significantly associated with DEP. The change in miR-144 was validated by RT-qPCR. NRF2 and its downstream antioxidant genes [glutamate cysteine ligase catalytic subunit (GCLC) and NAD(P)H:quinone oxidoreductase 1 (NQO1)] were negatively associated with miR-144 levels. Increases in miR-144 and miR-21 were associated with plasma 8-hydroxydeoxyguanosine 8-OHdG level and were blunted by antioxidant (i.e, DEN).Systemic miRNAs with plausible biological function are altered by acute moderate-dose DE exposure. Oxidative stress appears to mediate DE-associated changes in miR-144.
Thalamic Dysfunction in Schizophrenia Suggested by Whole-Night Deficits in Slow and Fast Spindles
Authors: Fabio Ferrarelli, Michael J. Peterson, Simone Sarasso, Brady A. Riedner, Michael J. Murphy, Ruth M. Benca, Pietro Bria, Ned H. Kalin, Giulio Tononi
Journal: American Journal of Psychiatry (2010)

Objective: Slow waves and sleep spindles are the two main oscillations occurring during non-REM sleep. While slow oscillations are primarily generated and modulated by the cortex, sleep spindles are initiated by the thalamic reticular nucleus and regulated by thalamo-reticular and thalamo-cortical circuits. In a recent high-density EEG study, the authors found that 18 medicated schizophrenia patients had reduced sleep spindles, compared with healthy and depressed subjects, during the first non-REM episode. In the present study, the authors investigated whether spindle deficits were present in a larger sample of schizophrenia patients, were consistent across the night, were related to antipsychotic medications, and were suggestive of impairments in specific neuronal circuits. Method: Whole-night high-density EEG recordings were performed in 49 schizophrenia patients, 20 nonschizophrenia patients receiving antipsychotic medication, and 44 healthy subjects. In addition to sleep spindles, several parameters of slow waves were assessed. Results: Schizophrenia patients had whole-night deficits in spindle power (12–16 Hz) and in slow (12–14 Hz) and fast (14–16 Hz) spindle amplitude, duration, number, and integrated activity in the prefrontal, centroparietal, and temporal regions. Integrated spindle activity and spindle number had the largest effect sizes (effect size: ≥2.21). In contrast, no slow wave deficits were found in schizophrenia patients. Conclusions: These results indicate that spindle deficits can be reliably established in schizophrenia, are stable across the night, are unlikely to be due to antipsychotic medications, and point to deficits in the thalamic reticular nucleus and thalamo-reticular circuits.
Philosophy for Medicine: Applications in a Clinical Context
Authors: Markku Timonen
Journal: BMJ (2004)

A lthough clinical medicine bristles with philosophical questions, in the moral decisions of everyday medical practice we do not always contemplate them very deeply, but rather make our judgments fairly intuitively. However, as Philosophy for Medicine emphasises, our intuitive moral thinking is by no means disconnected from philosophical theory. Eds Martyn Evans, Pekka Louhiala, Raimo Puustinen Radcliffe Medical Press, £21.95, pp 168 ISBN 1 85775 943 5 Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> The book is very easy to understand. It starts with an introductory section that frees the reader from … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Novel bilayer wound dressing composed of silicone rubber with particular micropores enhanced wound re-epithelialization and contraction
Authors: Rui Xu, Gaoxing Luo, Hesheng Xia, Weifeng He, Jian Zhao, Bo Liu, Jianglin Tan, Junyi Zhou, Daisong Liu, Yuzhen Wang, Zhihui Yao, Rixing Zhan, Sisi Yang, Jun Wu
Journal: Biomaterials (2014)
Primary Pulmonary Neoplasms in Beagle Dogs Exposed to Aerosols of 144Ce in Fused-Clay Particless2
Authors: F. F. Hahn, S. A. Benjamin, B. B. Boecker, T. L. Chiffelle, C. H. Hobbs, R. K. Jones, R. O. McClellan, J. A. Pickrell, H. C. Redman
Journal: JNCI Journal of the National Cancer Institute (1973)

To determine the effects of inhaled 144Ce, 126 Beagle dogs (including 15 controls) were exposed to aerosols of either 144Ce in fused clay or stable cerium in fused clay. To date, 15 dogs have died 143–410 days after inhalation exposure from radiation pneumonitis and pulmonary fibrosis. Primary pulmonary neoplasms caused the deaths of 5 dogs 750–1318 days after inhalation exposure. Calculated pulmonary radiation doses until death ranged from 23,000–48,000 rads. Pulmonary hemangiosarcomas were found in all 5 dogs and metastasis in 4. In addition, 1 dog had a pulmonary fibrosarcoma and another had a bronchiolo-alveolar carcinoma, both of which metastasized to the tracheobronchial lymph nodes. Only 3 dogs with similar initial lung burdens of 144Ce died without pulmonary neoplasms, at 186, 193, and 410 days after inhalation exposure. The 91 dogs exposed to 144Ce-fused clay and all controls have survived 239–1565 days after inhalation exposure including 44 surviving >750 days, with pulmonary radiation doses from 2–36,000 rads.
Histological and Ultrastructural Studies on Preserved Hearts
Authors: VICTOR J. FERRANS, SIDNEY LEVITSKY, L. MAXIMILIAN BUJA, WILLIS H. WILLIAMS, CHARLES L. MCINTOSH, WILLIAM C. ROBERTS
Journal: Circulation (1970)

Histological and ultrastructural studies were made on 17 excised canine hearts after 0 (control), 3, 14, 18, and 24 hours of preservation by perfusion with cold filtered plasma. These were correlated with function as measured by an isovolumetric balloon technique. Variations in structure and function were observed within each group of preserved hearts, but function and structure correlated well in individual hearts: when function was excellent, structure was excellent; when function was poor, changes in the sarcoplasmic reticulum and mitochondria were prominent. The presence of marked angulations in the mitochondrial cristae correlated with high dp/dt values. Interstitial edema was present in all preserved hearts. The three control hearts, one 3-hour heart, and two 14-hour hearts showed excellent morphology and function. Of the five 18-hour hearts, function and morphology were excellent in three and barely adequate in one; a severely damaged heart could not be defibrillated. Of the six 24-hour hearts, morphology and function were excellent in three and poor in two; one heart with diffuse mitochondrial damage could not be defibrillated. These studies demonstrate good morphological preservation of canine hearts for 24 hours.