tbuckley/cabot-search huggingface dataset:
Developmental aspects of the renal response to hypoxemia in the lamb fetus.
Authors: J E Robillard, R E Weitzman, L Burmeister, F G Smith
Journal: Circulation Research (1981)

The effects of fetal hypoxemia on renal hemodynamics and renal function were studied in two groups of chronically catheterized young (&lt; 120 days of gestation) and near-term lamb fetuses (&gt; 130 days). Fetal hypoxemia produced, in both groups, a significantly decrease in renal blood flow (RBF) and a significant increase in the filtration fraction. However, the glomerular filtration rate (GFR) did not change significantly suggesting that the renal vasoconstriction associated with fetal hypoxemia was more important at the efferent than at the afferent arteriolar level. In the group of near-term fetuses, the decrease in RBF correlated closely with changes in plasma renin activity (PRA) (r = 0.77). No changes in PRA were observed during hypoxemia in the group of young fetuses. After hypoxemia, reactive hyperemia associated with a significant increase in urinary prostaglandin excretion (PGE and PGF2 alpha) was observed in near-term fetuses but not in young fetuses. It also was demonstrated that fetal hypoxemia produced a significant increase in fetal plasma concentrations of vasopressin associated with an antidiuresis in all but one near-term fetus and in 50% of the young fetuses, suggesting that the ability of the fetal kidney to reabsorb free water is more developed in near-term fetuses. Finally, fetal hypoxemia had no effect on mean arterial pressure and heart rate in young fetuses; however, in near-term fetuses, a significant increase in blood pressure and a decrease in heart rate were observed. In summary, it appears that the response of the fetal kidney to hypoxemia depends on the degree of fetal maturation.
The imagined itch: brain circuitry supporting nocebo-induced itch in atopic dermatitis patients
Authors: V. Napadow, A. Li, M.L. Loggia, J. Kim, I. Mawla, G. Desbordes, P. C. Schalock, E. A. Lerner, T. N. Tran, J. Ring, B. R. Rosen, T. J. Kaptchuk, F. Pfab
Journal: Allergy (2015)

Background Psychological factors are known to significantly modulate itch in patients suffering from chronic itch. Itch is also highly susceptible to both placebo and nocebo (negative placebo) effects. Brain activity likely supports nocebo-induced itch, but is currently unknown. Methods We collected functional MRI (fMRI) data from atopic dermatitis (AD) patients, in a within-subject design, and contrast brain response to nocebo saline understood to be allergen vs open-label saline control. Exploratory analyses compared results to real allergen itch response and placebo responsiveness, evaluated in the same patients. Results Nocebo saline produced greater itch than open saline control (P < 0.01). Compared to open saline, nocebo saline demonstrated greater fMRI response in caudate, dorsolateral prefrontal cortex (dlPFC), and intraparietal sulcus (iPS) – brain regions important for cognitive executive and motivational processing. Exploratory analyses found that subjects with greater dlPFC and caudate activation to nocebo-induced itch also demonstrated greater dlPFC and caudate activation, respectively, for real allergen itch. Subjects reporting greater nocebo-induced itch also demonstrated greater placebo reduction of allergen-evoked itch, suggesting increased generalized modulation of itch perception. Conclusions Our study demonstrates the capacity of nocebo saline to mimic both the sensory and neural effects of real allergens and provides an insight to the brain mechanisms supporting nocebo-induced itch in AD, thus aiding our understanding of the role that expectations and other psychological factors play in modulating itch perception in chronic itch patients.
The Cost-Quality Trade-Off: Need for Data Quality Standards for Studies That Impact Clinical Practice and Health Policy
Authors: Jennifer L. Malin, Nancy L. Keating
Journal: Journal of Clinical Oncology (2005)

Observational studies of cancer patients often rely on existing administrative data such as insurance claims and cancer registry data. As researchers began to supplement administrative data with patient self-reported data or medical record review, limitations in the validity of these easily obtainable data sets began to emerge.
General practitioners' perceptions of effective health care
Authors: Z. Tomlin, C. Humphrey, S. Rogers
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objectives:</b> To explore general practitioners9 perceptions of effective health care and its application in their own practice; to examine how these perceptions relate to assumptions about clinicians9 values and behaviour implicit in the evidence based medicine approach. <b>Design:</b> A qualitative study using semistructured interviews. <b>Setting:</b> Eight general practices in North Thames region that were part of the Medical Research Council General Practice Research Framework. <b>Participants:</b> 24 general practitioners, three from each practice <b>Main outcome measures:</b> Respondents9 definitions of effective health care, reasons for not practising effectively according to their own criteria, sources of information used to answer clinical questions about patients, reasons for making changes in clinical practice. <b>Results:</b> Three categories of definitions emerged: clinical, patient related, and resource related. Patient factors were the main reason given for not practising effectively; others were lack of time, doctors9 lack of knowledge and skills, lack of resources, and “human failings.” Main sources of information used in situations of clinical uncertainty were general practitioner partners and hospital doctors. Contact with hospital doctors and observation of hospital practice were just as likely as information from medical and scientific literature to bring about changes in clinical practice. <b>Conclusions:</b> The findings suggest that the central assumptions of the evidence based medicine paradigm may not be shared by many general practitioners, making its application in general practice problematic. The promotion of effective care in general practice requires a broader vision and a more pragmatic approach which takes account of practitioners9concerns and is compatible with the complex nature of their work.
Noninvasive Renal Sympathetic Denervation by Extracorporeal High-Intensity Focused Ultrasound in a Pre-Clinical Canine Model
Authors: Qifeng Wang, Rui Guo, Shunkang Rong, Gang Yang, Que Zhu, Yonghong Jiang, Changming Deng, Dichuan Liu, Qi Zhou, Qi Wu, Shunhe Wang, Jun Qian, Qi Wang, Han Lei, Tong-Chuan He, Zhibiao Wang, Jing Huang
Journal: Journal of the American College of Cardiology (2013)
Letter: Kilopascals. Control of oral contraceptive clinical trails.
Authors: G D Mitchell
Journal: BMJ (1975)

To deal with the confusion surrounding clinical acceptability of specific oral contraceptive preparations, a single set of forms for use in clinical research, together with a set of definitions, was recommended. Senior representatives of major pharmaceutical companies engaging in clinical trials in the United Kingdom were invited to cooperate. The Family Planning Research Unit of the University of Exeter was requested to provide facilities for meetings which began in 1972. An agreed set of forms has been designed and set of definitions has been developed to make the collection and interpretation of data more efficient. Organizations carrying out oral contraceptive clinical trials are invited to contact this unit. Forms, definitions, and further information will be provided on request.
Phase II Study of Oral Capsular 4-Hydroxyphenylretinamide (4-HPR/Fenretinide) in Pediatric Patients with Refractory or Recurrent Neuroblastoma: A Report from the Children's Oncology Group
Authors: Judith G. Villablanca, Wendy B. London, Arlene Naranjo, Patrick McGrady, Matthew M. Ames, Joel M. Reid, Renee M. McGovern, Sarah A. Buhrow, Hollie Jackson, Enno Stranzinger, Brenda J. Kitchen, Paul M. Sondel, Marguerite T. Parisi, Barry Shulkin, Gregory A. Yanik, Susan L. Cohn, C. Patrick Reynolds
Journal: Clinical Cancer Research (2011)

Abstract Purpose: To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma. Experimental Design: Patients received 7 days of fenretinide: 2,475 mg/m2/d divided TID (&amp;lt;18 years) or 1,800 mg/m2/d divided BID (≥18 years) every 21 days for a maximum of 30 courses. Patients with stable or responding disease after course 30 could request additional compassionate courses. Best response by course 8 was evaluated in stratum 1 (measurable disease on CT/MRI ± bone marrow and/or MIBG avid sites) and stratum 2 (bone marrow and/or MIBG avid sites only). Results: Sixty-two eligible patients, median age 5 years (range 0.6–19.9), were treated in stratum 1 (n = 38) and stratum 2 (n = 24). One partial response (PR) was seen in stratum 2 (n = 24 evaluable). No responses were seen in stratum 1 (n = 35 evaluable). Prolonged stable disease (SD) was seen in 7 patients in stratum 1 and 6 patients in stratum 2 for 4 to 45+ (median 15) courses. Median time to progression was 40 days (range 17–506) for stratum 1 and 48 days (range 17–892) for stratum 2. Mean 4-HPR steady-state trough plasma concentrations were 7.25 μmol/L (coefficient of variation 40–56%) at day 7 course 1. Toxicities were mild and reversible. Conclusions: Although neither stratum met protocol criteria for efficacy, 1 PR + 13 prolonged SD occurred in 14/59 (24%) of evaluable patients. Low bioavailability may have limited fenretinide activity. Novel fenretinide formulations with improved bioavailability are currently in pediatric phase I studies. Clin Cancer Res; 17(21); 6858–66. ©2011 AACR.
Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP
Authors: Kenta Maruyama, Satoshi Uematsu, Takeshi Kondo, Osamu Takeuchi, Mikaël M. Martino, Takumi Kawasaki, Shizuo Akira
Journal: The Journal of Experimental Medicine (2013)

Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors in response to receptor activator of nuclear factor κB (NF-κB) ligand (RANKL). We found that RANKL induced expression of the DExD/H helicase family corepressor strawberry notch homologue 2 (Sbno2). Previous in vitro studies showed that Sbno2 is induced by IL-10 and is involved in NF-κB repression. However, the role of Sbno2 in vivo and its pleiotropic functions are unknown. Sbno2 gene targeting resulted in normal NF-κB activation by TLR ligands. However, Sbno2-deficient mice exhibited increased bone mass due to impaired osteoclast fusion. Expression of dendritic cell–specific transmembrane protein (DC-STAMP), a critical player in osteoclast fusion, was significantly attenuated, and cell fusion of Sbno2-deficient osteoclasts was rescued by DC-STAMP. Sbno2 directly bound to T cell acute lymphocytic leukemia 1 (Tal1) and attenuated its inhibition of DC-STAMP expression, leading to activation of the DC-STAMP promoter by microphthalmia-associated transcription factor (MITF). Thus, Sbno2 plays a pivotal role in bone homeostasis in vivo by fine-tuning osteoclast fusion.
INTESTINAL OBSTRUCTION
Authors: Lester R. Dragstedt, Carl A. Dragstedt, John T. McClintock, C. S. Chase
Journal: The Journal of Experimental Medicine (1919)

1. It is impossible to sterilize the intestine by the use of chemical antiseptics even when these are applied directly to the mucosa of isolated segments. 2. The mucosa of the alimentary tract does not elaborate an internal secretion which is necessary to life, or a secretion which could be disturbed by the conditions of acute obstruction so as to account for the symptom complex of that condition. 3. The substances responsible for the toxemia in acute obstruction are produced by the action of intestinal bacteria on proteins or their split products. 4. An injury to the intestinal mucosa, particularly that resulting from disturbances of the blood supply to the intestine, greatly facilitates the absorption of these poisons. The work of Hartwell and his associates and that of Murphy and Brooks on this point are confirmed.
Diagnostics of loss in lung elastic recoil pressure using impulse oscillometry and body plethysmography
Authors: Larisa Kiryukhina, Marina Kameneva
Journal: European Respiratory Journal (2011)

Respiratory resistance at 20 Hz (R20) by impulse oscillometry (IO) characterizes airways resistance with inextensible walls. Airways resistance (Rtot) by body plethysmography reflects the total resistance of the first 8 - 10 bronchi generations. These indicators by different methods are close physiologically. The airways in patients with an emphysema are deprived of elastic support, so a lung compliance (CL) considerably increases. We have assumed that shunting of R20 increases with loss of lung elastic recoil.

Aim of the study is evaluation loss of respiratory resistance by IO with increasing of compliance and decreasing of lung elastic recoil.

Materials and methods: We compared Rtot and R20 in 67 healthy volunteers (32F/35M, 47±1 yrs) and in the patients with obstructive disorders - 41 patients with COPD (0F/41M, 56±1 yrs) and 52 patients with bronchial asthma (34F/18M, 47±2 yrs). We have used the relation Rtot/R20. All patients were performed investigation of lung elasticity using esophagus balloon.

Results: Rtot/R20 in healthy group was 0,79±0,03 and in patients with obstructive disorders it was 1,72±0,10 (p<0,01). The analysis Rtot/R20 in patients with obstructive disorders showed considerable difference of Rtot/R20 value in patients with normal lung elastic recoil and in patients with loss lung elastic recoil (1,24 and 2,08 accordingly, p<0,01). The correlation analysis showed moderate dependence Rtot/R20 with CL and coefficient of retraction (CR) (r=0,57 and –0,38 accordingly, p < 0,01).

Conclusion: The relation Rtot/R20 reflects loss in parenchymal elastic recoil pressure. In healthy and patients with obstructive disorders with normal lung elastic recoil it is less 1,24.
Phase I Trial of Daily Oral Polyphenon E in Patients With Asymptomatic Rai Stage 0 to II Chronic Lymphocytic Leukemia
Authors: Tait D. Shanafelt, Tim G. Call, Clive S. Zent, Betsy LaPlant, Deborah A. Bowen, Michelle Roos, Charla R. Secreto, Asish K. Ghosh, Brian F. Kabat, Mao-Jung Lee, Chung S. Yang, Diane F. Jelinek, Charles Erlichman, Neil E. Kay
Journal: Journal of Clinical Oncology (2009)

To define the optimal dose of Polyphenon E for chronic daily administration and tolerability in patients with chronic lymphocytic leukemia (CLL).
WINES AND WINES
Authors: L. C. Johnston
Journal: BMJ (1915)

MTUL'T'IPLE LIPOMATA. AND ELEPHANTIASIS.SIR,--Dr.MNLarion Arclhibald's cae.w (Br.ITISH M\EDICAL JOURNALr, April 3td, 1).595) is of considerable interest an(l of soiie Vriety; judging by the descriptioni and photograph it belongs to tile grouLp described by Adamis in 1894 as "false hypertrophies."The ellarac- teristics of these ca-es are thi%t thiey are uot always Colngenlital; thiey are occasionally bilateral, thley are associated withi synidactylisimi and lipomatosis, anid in many cases are irreaularly progressiVe.These cases must be distinguislhed from true congenital clephiantiasis, wlhiclh is a conidition resemlbling the trophoedeima of Meige, anld is not associated withl multiple tuinours or otlher congenital defects, sucll as supernumlilerary digits.The swellinig of the superficial veins is interesting for two reasons: First, because Lmany of these cases are associated witlh naevi and angeiomuata, and seconidlv, because one theory of the causation of the lhypertroplly is that it-is dute to ani increased blood supply and venous en- gorgenient dependetnt on certain supposed clhangres in tlle coats of the arteries.The literature goes baek to 1858, at least, but no vory satisfactory explanation of these lhyper-troplhies lhas yet been fortlicoming.-Iami, etc.,
Simultaneously Measured Isometric Tension and ATP Hydrolysis in Glycerinated Fibers from Normal and Hypertrophied Rabbit Heart
Authors: PHILIP D. HENRY, Gail G. AHUMADA, WILLIAM F. FRIEDMAN, BURTON E. SOBEL
Journal: Circulation Research (1972)

Adenosinetriphosphatase (ATPase) activity, isometric tension, and sarcomere length of glycerinated fibers from 14 hypertrophied and 18 normal rabbit hearts were measured simultaneously to characterize the altered performance of hypertrophied myocardium. ATPase activity was assessed radiochromatographically, and contributions from mitochondria, sarcolemma, and sarcoplasmic reticulum were excluded. The active length-tension and the active tension-pCa relationships in fibers from hypertrophied myocardium were normal in sharp contrast to the depressed active length-tension curves in corresponding intact papillary muscles. Total ATPase activity associated with contraction at a given developed tension was decreased significantly in fibers from hypertrophied hearts ( P &lt;0.001). ATPase activity was diminished in glycerinated myofibrils, actomyosin, and homogenates from hypertrophied hearts as well. On the other hand, the increase in ATPase activity associated with a given increase in developed tension was virtually identical in fibers from hypertrophied and normal hearts. Thus, depressed total ATPase activity in glycerinated fibers from hypertrophied hearts does not appear to impair maintenance of isometric tension.
Lyt-2 and lyt-3 antigens are on two different polypeptide subunits linked by disulfide bonds. Relationship of subunits to T cell cytolytic activity.
Authors: J A Ledbetter, W E Seaman, T T Tsu, L A Herzenberg
Journal: The Journal of Experimental Medicine (1981)

Lyt-2 and Lyt-3 antigens are carried on separate disulfide-bonded subunits of the same cell surface macromolecules. These are present on thymocytes in a variety of multimeric forms consisting of disulfide-bonded dimers, tetramers, and hexamers of pairwise combinations of three subunits (30,000, 34,000, and 38,000 Mr). From reduced and alkylated Nonidet-P40 thymus extracts, a monoclonal anti-Lyt-3 precipitates only the 30,000 Mr subunit, but not the 30,000 Mr subunit. Almost all of the Lyt-2 and Lyt-3 subunits on the cell are covalently linked by disulfide bonds. However, small amounts of free Lyt-3 subunit was seen in some experiments. Similarly, small amounts of Lyt-2-3- material, consisting of dimers of the 38,000 and 34,000 Mr subunits were identified. Each of the three subunits migrated with a basic charge (pI greater than 8) on two-dimensional gels. Cytotoxic effector cells that are blocked by anti-Lyt-2 and anti-3 can be treated with trypsin and other arginine-specific proteases to remove these antigens. At low concentrations of these proteases, Lyt-3 antigens are selectively removed. After selective removal of Lyt-3 antigens, cytotoxic effector cells are still active and blocking of activity by anti-Lyt-3 is significantly reduced, whereas blocking of activity by anti-Lyt-2 is significantly increased. Neither Lyt-2 nor Lyt-3 is allelically excluded on thymocytes or T cells. These results suggested that the Lyt-2, Lyt-3 macromolecules are associated with but do not serve as the T cell antigen receptor.
Effect of Knowledge of APOE Genotype on Subjective and Objective Memory Performance in Healthy Older Adults
Authors: Tara T. Lineweaver, Mark W. Bondi, Douglas Galasko, David P. Salmon
Journal: American Journal of Psychiatry (2013)

The knowledge that one carries the apolipoprotein E (APOE) ε4 allele risk factor for Alzheimer's disease was recently found to have little short-term psychological risk. The authors investigated the impact of knowledge of carrying the risk allele on subjective ratings of memory and objective memory test performance of older adults.Using a nested case-control design, the authors administered objective verbal and visual memory tests and self-rating scales of memory function to 144 cognitively normal older adults (ages 52-89) with known APOE genotype who knew (ε4+, N=25; ε4-, N=49) or did not know (ε4+, N=25; ε4-, N=45) their genotype and genetic risk for Alzheimer's disease prior to neuropsychological evaluation.Significant genotype-by-disclosure interaction effects were observed on several memory rating scales and tests of immediate and delayed verbal recall. Older adults who knew their ε4+ genotype judged their memory more harshly and performed worse on an objective verbal memory test than did ε4+ adults who did not know. In contrast, older adults who knew their ε4- genotype judged their memory more positively than did ε4- adults who did not know, but these groups did not differ in objective memory test performance.Informing older adults that they have an APOE genotype associated with an increased risk of Alzheimer's disease can have adverse consequences on their perception of their memory abilities and their performance on objective memory tests. The patient's knowledge of his or her genotype and risk of Alzheimer's disease should be considered when evaluating cognition in the elderly.
NHS reorganisations: who's kicking whom, who's protesting?: Will and power
Authors: D Mark Jackson
Journal: BMJ (2006)

EDITOR—Godlee laments the demise of medical professionalism in the NHS and quotes Greener, who wonders whether doctors have lost the will or power to stop believe to be vandalism.1 2

They have certainly lost the power and with it, of course, the will, because politicians have long believed, as accountable guardians of public finance, that they have a duty to cull the influence of the medical profession on healthcare provision. The medical profession was uncontrolled by Bevan, and thereafter proved to be a …
Clinical Relevance of BCL2, BCL6, and MYC Rearrangements in Diffuse Large B-Cell Lymphoma
Authors: M.H.H. Kramer, J. Hermans, E. Wijburg, K. Philippo, E. Geelen, J.H.J.M. van Krieken, D. de Jong, E. Maartense, E. Schuuring, P.M. Kluin
Journal: Blood (1998)
A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis
Authors: Gavin Giovannoni, Giancarlo Comi, Stuart Cook, Kottil Rammohan, Peter Rieckmann, Per Soelberg Sørensen, Patrick Vermersch, Peter Chang, Anthony Hamlett, Bruno Musch, Steven J. Greenberg
Journal: New England Journal of Medicine (2010)

Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis.We randomly assigned 1326 patients in an approximate 1:1:1 ratio to receive one of two cumulative doses of cladribine tablets (either 3.5 mg or 5.25 mg per kilogram of body weight) or matching placebo, given in two or four short courses for the first 48 weeks, then in two short courses starting at week 48 and week 52 (for a total of 8 to 20 days per year). The primary end point was the rate of relapse at 96 weeks.Among patients who received cladribine tablets (either 3.5 mg or 5.25 mg per kilogram), there was a significantly lower annualized rate of relapse than in the placebo group (0.14 and 0.15, respectively, vs. 0.33; P<0.001 for both comparisons), a higher relapse-free rate (79.7% and 78.9%, respectively, vs. 60.9%; P<0.001 for both comparisons), a lower risk of 3-month sustained progression of disability (hazard ratio for the 3.5-mg group, 0.67; 95% confidence interval [CI], 0.48 to 0.93; P=0.02; and hazard ratio for the 5.25-mg group, 0.69; 95% CI, 0.49 to 0.96; P=0.03), and significant reductions in the brain lesion count on magnetic resonance imaging (MRI) (P<0.001 for all comparisons). Adverse events that were more frequent in the cladribine groups included lymphocytopenia (21.6% in the 3.5-mg group and 31.5% in the 5.25-mg group, vs. 1.8%) and herpes zoster (8 patients and 12 patients, respectively, vs. no patients).Treatment with cladribine tablets significantly reduced relapse rates, the risk of disability progression, and MRI measures of disease activity at 96 weeks. The benefits need to be weighed against the risks. (ClinicalTrials.gov number, NCT00213135.)