tbuckley/cabot-search huggingface dataset:
Protein 4.1R–deficient mice are viable but have erythroid membrane skeleton abnormalities
Authors: Zheng-Tao Shi, Veena Afzal, Barry Coller, Dipti Patel, Joel A. Chasis, Marilyn Parra, Gloria Lee, Chris Paszty, Mary Stevens, Loren Walensky, Luanne L. Peters, Narla Mohandas, Edward Rubin, John G. Conboy
Journal: Journal of Clinical Investigation (1999)

A diverse family of protein 4.1R isoforms is encoded by a complex gene on human chromosome 1. Although the prototypical 80-kDa 4.1R in mature erythrocytes is a key component of the erythroid membrane skeleton that regulates erythrocyte morphology and mechanical stability, little is known about 4.1R function in nucleated cells. Using gene knockout technology, we have generated mice with complete deficiency of all 4.1R protein isoforms. These 4.1R-null mice were viable, with moderate hemolytic anemia but no gross abnormalities. Erythrocytes from these mice exhibited abnormal morphology, lowered membrane stability, and reduced expression of other skeletal proteins including spectrin and ankyrin, suggesting that loss of 4.1R compromises membrane skeleton assembly in erythroid progenitors. Platelet morphology and function were essentially normal, indicating that 4.1R deficiency may have less impact on other hematopoietic lineages. Nonerythroid 4.1R expression patterns, viewed using histochemical staining for lacZ reporter activity incorporated into the targeted gene, revealed focal expression in specific neurons in the brain and in select cells of other major organs, challenging the view that 4.1R expression is widespread among nonerythroid cells. The 4.1R knockout mice represent a valuable animal model for exploring 4.1R function in nonerythroid cells and for determining pathophysiological sequelae to 4.1R deficiency.
Disputes Between Medical Supervisors and Trainees
Authors: John Glasson
Journal: JAMA (1994)

THE RELATIONSHIP between medical students, resident physicians, and their supervisors is a major factor determining the quality of medical education. For this relationship to be most conducive to learning, medical supervisors and trainees must communicate openly, share clearly defined conceptions of their respective roles in patient care and within the larger teacher-learner relationship,<sup>1</sup>and interact with each other and with patients in "a climate of trust and concern."2 Fostering such a relationship is an important goal of medical education. Unfortunately, evidence suggests that too often this idealistic model is not realized in practice.<sup>3-11</sup>When disputes arise between medical students, resident physicians, and supervising physicians, they often can be resolved through open and honest communication and informal negotiation.<sup>12</sup>When disputes cannot be resolved by the individual parties, resolution may require recourse to formal mechanisms that follow the requirements of due process. Due process for fair resolution of disputes between medical students,
Randomized controlled trial of desmopressin plus terlipressin vs. terlipressin alone for the treatment of acute variceal hemorrhage in cirrhotic patients: A multicenter, double-blind study
Authors: Roberto de Franchis, Paolo G. Arcidiacono, Luca Carpinelli, Bruno Andreoni, Lorenzo Cestari, Sergio Brunati, Alessandro Zambelli, Giorgio Battaglia, Pier M. Mannucci
Journal: Hepatology (1993)

1-Deamino-8-D-arginine vasopressin (DDAVP, desmopressin), a synthetic analog of the antidiuretic hormone l-arginine vasopressin, improves hemostasis parameters in cirrhotic patients. Hence its use in combination with a vasoactive drug such as terlipressin might improve the performance of this drug in controlling variceal bleeding. The aim of this trial was to compare the efficacy of desmopressin plus terlipressin with that of terlipressin alone in controlling acute variceal hemorrhage. Cirrhotic patients with active variceal hemorrhage diagnosed endoscopically were randomized within 2 hr of admission to receive desmopressin plus terlipressin or placebo plus terlipressin. Terlipressin (2 mg, intravenous bolus) was given at time 0 and every 4 hr thereafter for 24 hr. Desmopressin (0.3 μg/kg, intravenously) or placebo was given in saline solution over 30 min at time 0 and at 26 hr. Patients were monitored for 24 hr after cessation of treatment. Treatment failure was defined as recurrence of active bleeding during treatment or within the 24 hr after treatment. After enrolling 51 of the planned 84 patients, we carried out an interim analysis. Treatment failure occurred in 13 of 24 patients randomized to receive desmopressin plus terlipressin (54.2%) and in 6 of 22 patients randomized to receive terlipressin (27.3%) (p = 0.06, Fisher’s exact test). The trial was interrupted at this stage because patients treated with the “new” therapy fared worse than those treated with the standard therapy, and the possibility of reversing this trend by completing the trial was deemed remote. The addition of desmopressin does not improve and may worsen the efficacy of terlipressin in controlling acute variceal bleeding in cirrhotic patients. (HEPATOLOGY 1993;18:1102-1107).
Palliative care in Scotland is too focused on cancer, says national report
Authors: A. O'Dowd
Journal: BMJ (2008)

Palliative care services in Scotland are too biased towards cancer, at the expense of other incurable illnesses, finds a report by the country’s public sector spending watchdog.

The Audit Scotland report, published last week, looked at the provision of care for people with terminal illnesses. It concluded that access was uneven across the country and needed to improve.

It found that 90% of specialist care was given to cancer patients but that the disease represented less than 30% of deaths.

“Historically, palliative care near the end of life was mainly offered to cancer …
Early Telomere Shortening and Genomic Instability in Tubo-Ovarian Preneoplastic Lesions
Authors: Gautier Chene, Andrei Tchirkov, Eleonore Pierre-Eymard, Jacques Dauplat, Ines Raoelfils, Anne Cayre, Emmanuel Watkin, Philippe Vago, Frederique Penault-Llorca
Journal: Clinical Cancer Research (2013)

Genetic instability plays an important role in ovarian carcinogenesis. We investigated the level of telomere shortening and genomic instability in early and preinvasive stages of ovarian cancer, serous tubal intraepithelial carcinoma (STIC), and tubo-ovarian dysplasia (TOD).Fifty-one TOD from prophylactic salpingo-oophorectomies with BRCA1 or 2 mutation, 12 STICs, 53 tubo-ovarian high-grade serous carcinoma, and 36 noncancerous controls were laser capture microdissected from formalin-fixed, paraffin-embedded sections, analyzed by comparative genomic hybridization (array CGH) and for telomere length (using quantitative real-time PCR based on the Cawthon's method). TOD and STICs were defined by morphologic scores and immunohistochemical expressions of p53, Ki67, and γH2AX.TOD showed marked telomere shortening compared with noncancerous controls (P < 10(-7)). STICs had even shorter telomeres than TOD (P = 0.0008). Ovarian carcinoma had shorter telomeres than controls but longer than STICs and dysplasia. In TOD, telomeres were significantly shorter in those with BRCA1 mutation than in those with BRCA2 mutation (P = 0.005). In addition, γH2AX expression in TOD and STIC groups with short telomeres was significantly increased (P < 10(-7)). In dysplastic epithelium, we found subtle genomic alterations, in contrast to more important genomic imbalances in STICs. The total number of genetic alterations was the highest in ovarian cancers.These findings suggest that genetic instability occurs in early stages of ovarian tumorigenesis. STICs and noninvasive dysplasia are likely an important step in early serous ovarian neoplasia.
Three-dimensional echocardiography. In vivo validation for left ventricular volume and function.
Authors: S C Siu, J M Rivera, J L Guerrero, M D Handschumacher, J P Lethor, A E Weyman, R A Levine, M H Picard
Journal: Circulation (1993)

BACKGROUND Current two-dimensional quantitative echocardiographic methods of volume assessment require image acquisition from standardized scanning planes. Left ventricular volume and ejection fraction are then calculated by assuming ventricular symmetry and geometry. These assumptions may not be valid in distorted ventricles. Three-dimensional echocardiography can quantify left ventricular volume without the limitations imposed by the assumptions of two-dimensional methods. We have developed a three-dimensional system that automatically integrates two-dimensional echocardiographic images and their positions in real time and calculates left ventricular volume directly from traced endocardial contours without geometric assumptions. METHODS AND RESULTS To study the accuracy of this method in quantifying left ventricular volume and performance in vivo, a canine model was developed in which instantaneous left ventricular volume can be measured directly with an intracavitary balloon connected to an external column. Ten dogs were studied at 84 different cavity volumes (4 to 85 cm3) and in conditions of altered left ventricular shape produced by either coronary occlusion or right ventricular volume overload. To demonstrate clinical feasibility, 19 adult human subjects were then studied by this method for quantification of stroke volume. Left ventricular volume, stroke volume, and ejection fraction calculated by three-dimensional echocardiography correlated well with directly measured values (r = .98, .96, .96 for volume, stroke volume, and ejection fraction, respectively) and agreed closely with them (mean difference, -0.78 cm3, -0.60 cm3, -0.32%). In humans, there was a good correlation (r = .94, SEE = 4.29 cm3) and agreement (mean difference, -0.98 +/- 4.2 cm3) between three-dimensional echocardiography and Doppler-derived stroke volumes. CONCLUSIONS Three-dimensional echocardiography allows accurate assessment of left ventricular volume and systolic function.
Expiratory flow limitation during exercise in COPD: detection by manual compression of the abdominal wall
Authors: S. Abdel Kafi, T. Sersté, D. Leduc, R. Sergysels, V. Ninane
Journal: European Respiratory Journal (2002)

Manual compression of the abdomen (MCA) during spontaneous expiration is a simple method for the detection of flow limitation in the chronic obstructive pulmonary disease (COPD) patients during resting breathing, based on comparison of flow/volume curves obtained during MCA with that of the preceding control breath. It was assessed whether this nonstandardized technique is also feasible during exercise. MCA was performed during resting breathing and constant-exercise work at one- and two-thirds maximal mechanical power output ( W ′ max ) in six normal subjects and 12 COPD patients. Changes in end-expiratory lung volume (EELV) were also studied. With the aid of inspection, abdominal palpation and lung auscultation, MCA could always be applied during expiration. Flow limitation was never detected in the six normal subjects, whereas four of the COPD patients were flow limited at rest, seven during exercise at one-third W ′ max and nine during exercise at two-thirds W ′ max . Expiratory flow limitation detected by MCA was always associated with an increase in EELV during exercise, indicating dynamic hyperinflation occurrence or increase. It is concluded that manual compression of the abdomen is a very simple and reliable method for the detection of flow limitation during exercise.
Stability of insulin-induced gastric secretion after vagotomy.
Authors: R G Faber, J V Parkin, P Whitfied, M Hobsley
Journal: Gut (1975)

Gastric secretory response to insulin-induced hypoglycaemia was stuided in 21 subjects following vagotomy and a drainage procedure for duodenal ulcer. Eighteen subjects had one early test, ie, within one month of operation, and at least one late test, ie, six months or more after operation. Seven subjects had at least two late tests. When the insulin test results were expressed in terms of their Hollander status,there was as much variability with time as expected from previous reports. However, when results were expressed in terms of new criteria, decribed in the previous paper, the insulin status of postvagotomy patients remained constant with time.
Anxiety accelerates T-helper 2-tilted immune responses in patients with atopic dermatitis
Authors: H. Hashizume, T. Horibe, A. Ohshima, T. Ito, H. Yagi, M. Takigawa
Journal: British Journal of Dermatology (2005)

Stress, which mediates anxiety, worsens skin symptoms in patients with atopic dermatitis (AD). The contribution of anxiety to immune dysfunction, which plays a critical role in the pathogenesis of AD, requires clarification.To examine the relationship between anxiety and atopy-relevant immune function in AD.Eighty-five patients with AD and 58 normal individuals without a history of allergic disorders were enrolled in this study. To assess anxiety, the state-trait anxiety inventory was completed for both groups. In the AD group, measurements were made of SCORAD scores, serum IgE levels, itching (visual analogue scale), blood eosinophil count and T-helper (Th) 1/Th2 ratio in the peripheral blood.Anxiety was significantly higher among the subjects with AD than the normal subjects, and trait anxiety (TA) was higher than state anxiety (SA) in the AD group. Serum total IgE levels were correlated positively with TA and the TA/SA ratio and inversely with SA, and the Th1/Th2 ratio was correlated inversely with TA and the TA/SA ratio.The patients with AD had higher anxiety levels than normal individuals, and those with a stronger perception of TA than SA showed enhanced serum IgE synthesis and Th2 shifting.
Molecular Homology and the Luminal Transport of Hg2+ in the Renal Proximal Tubule
Authors: VERNON T. CANNON, DELON W. BARFUSS, RUDOLFS K. ZALUPS
Journal: Journal of the American Society of Nephrology (2000)

The aim of this study was to define mechanisms involved in the luminal uptake of inorganic mercury in the kidney using isolated perfused straight (S2) segments of the proximal tubule. When mercuric conjugates of glutathione (GSH), cysteinylglycine. or cysteine (containing 203Hg2+) were perfused through the lumen, the rates of luminal disappearance flux (JD) of inorganic mercury were approximately 39, 53, and 102 fmol/min per' min, respectively. Thus, the rates of luminal uptake of mercury are greater when the mercury is in the form of a mercuric conjugate of cysteine than in the form of a mercuric conjugate of cysteinylglycine or GSH. Addition of acivicin to the perfusate, to inhibit activity of the y-glutamyltransferase, caused significant reductions in the J,, for mercury in tubules perfused with mercuric conjugates of GSH. Addition of cilastatin, an inhibitor of dehydropeptidase- l (cysteinylglycinase) activity, caused significant reductions in the uptake of mercury in tubules perfused with mercuric conjugates of cysteinylglycine. These findings indicate that a significant amount of the luminal uptake of mercury, when mercuric conjugates of GSH are present in the lumen, is dependent on the activity of both y-glutamyltransferase and cysteinylglycinase. Finally, the JD for mercury in tubules perfused with mercuric conjugates of cysteine was reduced by approximately 50% when 3.0 mM L-lysine or 5.0 mM cycloleucine was added to the perfusate. It is concluded that these findings indicate that at least some of the luminal uptake of mercuric conjugates of cysteine occurs at the site of one or more amino acid transporters via a mechanism involving molecular homology.
Lower levels of hsa-mir-15a, which decreases VEGFA, in the CD4+ T cells of pediatric patients with asthma
Authors: Taiji Nakano, Yuzaburo Inoue, Naoki Shimojo, Fumiya Yamaide, Yoshinori Morita, Takayasu Arima, Minako Tomiita, Yoichi Kohno
Journal: Journal of Allergy and Clinical Immunology (2013)
IL-18–induced CD83<b>+</b>CCR7<b>+</b> NK helper cells
Authors: Robbie B. Mailliard, Sean M. Alber, Hongmei Shen, Simon C. Watkins, John M. Kirkwood, Ronald B. Herberman, Pawel Kalinski
Journal: The Journal of Experimental Medicine (2005)

In addition to their cytotoxic activities, natural killer (NK) cells can have immunoregulatory functions. We describe a distinct “helper” differentiation pathway of human CD56+CD3− NK cells into CD56+/CD83+/CCR7+/CD25+ cells that display high migratory responsiveness to lymph node (LN)–associated chemokines, high ability to produce interferon-γ upon exposure to dendritic cell (DC)- or T helper (Th) cell–related signals, and pronounced abilities to promote interleukin (IL)-12p70 production in DCs and the development of Th1 responses. This helper pathway of NK cell differentiation, which is not associated with any enhancement of cytolytic activity, is induced by IL-18, but not other NK cell–activating factors. It is blocked by prostaglandin (PG)E2, a factor that induces a similar CD83+/CCR7+/CD25+ LN-homing phenotype in maturing DCs. The current data demonstrate independent regulation of the “helper” versus “effector” pathways of NK cell differentiation and novel mechanisms of immunoregulation by IL-18 and PGE2.
Heme oxygenase-1 expression inhibits dendritic cell maturation and proinflammatory function but conserves IL-10 expression
Authors: Christine Chauveau, Séverine Rémy, Pierre Joseph Royer, Marcelo Hill, Séverine Tanguy-Royer, François-Xavier Hubert, Laurent Tesson, Régis Brion, Gaëlle Beriou, Marc Gregoire, Régis Josien, Maria Cristina Cuturi, Ignacio Anegon
Journal: Blood (2005)
Effect of acarbose, pectin, a combination of acarbose with pectin, and placebo on postprandial reactive hypoglycaemia after gastric surgery.
Authors: P A Speth, J B Jansen, C B Lamers
Journal: Gut (1983)

In a double-blind study we have compared the effect of 50 mg acarbose, 100 mg acarbose, 4.2 g pectin, a combination of 50 mg acarbose with 4.2 g pectin, and placebo on plasma glucose, plasma insulin, breath hydrogen and hypoglycaemic symptoms after a normal carbohydrate rich meal in nine patients with previous gastric surgery. Fifty milligrams acarbose, 100 mg acarbose and the combination of 50 mg acarbose with 4.2 g pectin significantly inhibited the postprandial peak glucose concentration (p less than 0.01). The lowest plasma glucose concentration, observed 60-150 minutes after ingestion of the meal, was significantly increased by the addition of 50 mg acarbose (p less than 0.01) and the combination of acarbose with pectin (p less than 0.05). The combination of acarbose with pectin was the only treatment that significantly inhibited the plasma insulin peak (p less than 0.05). Eight of nine patients had symptoms of hypoglycaemia on placebo, two on 50 mg acarbose (p less than 0.05), two on 100 mg acarbose (p less than 0.05), five on pectin (ns), and two on the combination of acarbose and pectin (p less than 0.05). All treatments with acarbose induced significant increases in breath hydrogen excretion (p less than 0.05).
Discordance between TSTs and IFN- release assays: the role of NTM and the relevance of mycobacterial sensitins
Authors: M. Tebruegge, T. Connell, N. Ritz, P.A. Bryant, N. Curtis
Journal: European Respiratory Journal (2010)

Discordance between TSTs and IFN-c release assays: the role of NTM and the relevance of mycobacterial sensitinsTo the Editors:We read with interest the recent study by LATORRE et al. [1] entitled ''Evaluating the non-tuberculous mycobacteria effect in the tuberculosis infection diagnosis''.We agree that discordance between tuberculin skin tests (TSTs) and interferon (IFN)-c release assays (IGRAs) presents physicians with a considerable management dilemma when evaluating children for latent tuberculosis (TB) infection (LTBI) in routine clinical practice.We have previously urged caution in the interpretation of discordant results and have highlighted this area as a research priority [2, 3].We therefore commend the authors for investigating a potential underlying cause of discordance.However, we believe that the interpretation of the data presented by LATORRE et al. [1] is based on erroneous assumptions, and that as a result the conclusions are overstated.We suggest that a more cautious and contextualised interpretation of the study findings is warranted.
Erythroplasia of Queyrat. Treatment with topically applied fluorouracil
Authors: D. K. Goette
Journal: JAMA (1975)

Three patients with biopsy-confirmed erythroplasia of Queyrat were treated with topically applied fluorouracil. The lesions cleared completely, and recurrence-free follow-up periods ranged from 20 to 60 months. There were normal histological findings in posttreatment biopsy specimens in two of the patients. A literature review yielded five additional cases successfully treated with fluorouracil applied topically. Patients with histologically confirmed erythroplasia of Queyrat should be afforded treatment with topically applied fluorouracil, as results appear to be superior to those of surgical or radiological treatment, with less morbidity.
Bismuth subsalicylate in the treatment of H2 blocker resistant duodenal ulcers: role of Helicobacter pylori.
Authors: S Wagner, M Gebel, K Haruma, W Bar, P Lange, J Freise, U Gladziwa, F W Schmidt
Journal: Gut (1992)

Fifty nine patients with Helicobacter pylori positive duodenal ulcers that failed to heal after a six week course of treatment with H2 blockers were randomly assigned to one of the following three regimens: (i) bismuth subsalicylate, 600 mg three times daily (n = 19), (ii) ranitidine, 300 mg at night (n = 20), (iii) bismuth subsalicylate plus ranitidine (n = 20). Cumulative ulcer healing rates after four and eight weeks respectively were as follows: bismuth subsalicylate 74% (14/19) and 95% (18/19), ranitidine 40% (8/20) and 65% (13/20), bismuth subsalicylate plus ranitidine 80% (16/20) and 95% (19/20). Bismuth subsalicylate treatment was better than ranitidine at both four and at eight weeks (p less than 0.05). The clearance rates for H pylori after four weeks were: bismuth subsubsalicylate 58%, ranitidine 0%, bismuth subsalicylate plus ranitidine 55%. After stopping bismuth therapy bacterial recrudescence frequently occurred. After bismuth treatment 86% (19/22) of ulcers had healed if H pylori had been cleared, whereas only 65% (11/17) had healed if H pylori persisted (NS). This study shows that bismuth subsalicylate is more effective in the treatment of resistant duodenal ulcers than standard dose ranitidine. It may be that suppression of H pylori by bismuth subsalicylate promotes ulcer healing.
A polymorphism in CTLA-4 is associated with the presence of anti-CYP2E1 antibody titres in patients with alcoholic liver disease
Authors: S.F. Stewart, A.K. Daly, Y. Chen, J.B. Leathart, D.E.J. Jones, R. Rolla, D. Vay, E. Mottaran, M. Vidali, E. Albano, C.P. Day
Journal: Journal of Hepatology (2001)