tbuckley/cabot-search huggingface dataset:
Addition of α<sub>1</sub>-Antitrypsin to Surfactant Improves Oxygenation in Surfactant-deficient Rats
Authors: YITZHAK BELAI, JOSÉ M. HERNÁNDEZ-JUVIEL, ROBERTA BRUNI, ALAN J. WARING, FRANS J. WALTHER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

During its life cycle, surfactant converts from highly surface active, large aggregates to less surface active, smaller aggregates. This process is probably regulated by a serine protease. We tested whether adding α1-antitrypsin ( α1-AT), an antiprotease, to surfactant improves its in vivo function. α1-AT was added to Survanta, to a standard phospholipid (PL) mixture, and to a synthetic surfactant (BC mixture = PL mixture + synthetic surfactant proteins B and C) at a dose of 100 mg α1-AT per 75 mg PL. Adding α1-AT did not affect in vitro surface activity, except for that of the PL mixture. Adult rats were ventilated with 100% O2, at a tidal volume of 7.5 ml/kg and a ventilatory rate of 60 breaths/ min. The rats' lungs were lavaged with saline until the PaO2 dropped below 100 mm Hg, at which time 100 mg/kg of surfactant with or without α1-AT or α1-AT alone was instilled. After 1 h of ventilation the rats were killed, pressure–volume curves were generated, and the rats' lungs were relavaged. Surfactant treatment improved oxygenation in the order: BC mixture > Survanta > PL mixture. Addition of α1-AT equalized oxygenation in all three α1-AT groups, but decreased respiratory system compliance in the groups given Survanta and PL mixture. Particle sizing of the final lung lavages showed preservation of large surfactant aggregates after treatment with α1-AT. These data suggest that the addition of α1-AT to surfactant can exert a positive effect on oxygenation and surfactant metabolism in surfactant-deficient rats.
Alternatives and defaults: Knobe's two explanations of how moral judgments influence intuitions about intentionality and causation
Authors: Walter Sinnott-Armstrong
Journal: Behavioral and Brain Sciences (2010)

Abstract Knobe cites both relevant alternatives and defaults on a continuum to explain how moral judgments influence intuitions about certain apparently non-moral notions. I ask (1) how these two accounts are related, (2) whether they exclude or supplement supposedly competing theories, and (3) how to get positive evidence that people consider relevant alternatives when applying such notions.
PET Studies of the Influences of Nicotine on Neural Systems in Cigarette Smokers
Authors: Jed E. Rose, Frederique M. Behm, Eric C. Westman, Roy J. Mathew, Edythe D. London, Thomas C. Hawk, Timothy G. Turkington, R. Edward Coleman
Journal: American Journal of Psychiatry (2003)

The effects of acute nicotine administration and smoking on brain function were investigated in two studies, with the primary goal of identifying neural systems that mediate these effects.In study 1, 18 healthy volunteer cigarette smokers were exposed to three conditions in a single session: 1) smoking a nicotine-containing cigarette, 2) smoking a denicotinized cigarette, or 3) receiving intravenous nicotine injections in conjunction with smoking a denicotinized cigarette. In study 2, 16 subjects smoked a nicotine-containing and denicotinized cigarette in each of two sessions 2 hours after receiving the nicotinic antagonist mecamylamine (10 mg) or placebo orally. Regional cerebral blood flow (rCBF) was assessed by using the bolus (15)O-labeled water method and positron emission tomography. Subjective measures of smoking withdrawal symptoms were also collected.A principal-components analysis of rCBF data pooled from the two studies identified three factors consisting of frontal, striatal, and reticular systems. The amygdala was considered as a separate region of interest. Nicotine increased normalized rCBF in the left frontal region and decreased rCBF in the left amygdala. The rCBF in the right hemisphere reticular system was related to nicotine dose in an inverted-U-shaped pattern and was strongly related to self-reported craving for cigarettes and to the addiction scale of a smoking motivation questionnaire. The effects of mecamylamine on rCBF were generally opposite to those of nicotine.The results indicate that nicotine influences brain regions involved in arousal and reward and suggest specific functional systems that may be linked to motivationally significant aspects of tobacco dependence.
Not necessarily ...
Authors: Norman R Williams
Journal: BMJ (2008)

Spence says that an individual patient, despite many years of investment in taking statins, gets virtually nil health benefit.1 This is not necessarily so. Clinical trials cannot determine if the benefit is confined to a few individuals or distributed among many. Statins might prevent (or delay) cardiovascular death in a handful of those who take them, or they might slightly reduce the risk in everyone who takes them.

To use an analogy, wearing thermal underwear in winter might prevent death due to hypothermia in only a few, but the benefit of keeping warm would be felt by many.

No conflict of interest is declared, as I do not take statins or wear thermal underwear.
Relations between upper abdominal symptoms and gastric distension abnormalities in dysmotility like functional dyspepsia and after vagotomy.
Authors: L E Troncon, D G Thompson, N K Ahluwalia, J Barlow, L Heggie
Journal: Gut (1995)

Postprandial bloating and fullness are commonly found both in dysmotility like functional dyspepsia, and after vagotomy but the relation between gastric accommodation and symptom production has not been investigated. Intragastric pressure levels and symptoms developed during controlled distension of the gastric fundus were recorded in nine patients with functional dyspepsia, in seven patients after truncal vagotomy, and in 11 healthy volunteers. The procedure was repeated after ingestion of a liquid nutrient meal (250 ml; 250 kcal). Gastric tone, expressed as the average value of pressure over the distension period was lower in controls (median: 11.3 mm Hg) than in either the dyspeptic patients (median: 16.48 mm Hg) or postvagotomy patients (median: 19.12 mm Hg) (p < 0.05). Meal ingestion reduced gastric tone in controls, but no significant change occurred in either the dyspepsia or the postvagotomy patients. Volumes at which discomfort was elicited by distension during fasting were lower both in dyspeptic patients (median: 210 ml) and in postvagotomy patients (median: 180 ml) than in healthy volunteers (median: 660 ml) (p < 0.05). Discomfort thresholds were unaffected by meal ingestion. These results suggest that a disturbance of gastric relaxation may be related to symptom development in dysmotility like functional dyspepsia, while similarities between dyspeptic patients and postvagotomy patients suggest that the impaired gastric accommodation in functional dyspepsia may be due to an underlying vagal defect.
Medical school applications---a critical situation
Authors: I C McManus
Journal: BMJ (2002)

Medical schools need well qualified, well motivated medical students. Admissions tutors, their desks piled high with applications, usually worry little about a dearth of applicants. Nevertheless, because each applicant applies to four schools, the surfeit is largely illusory. The statistics of the Universities and Colleges Admissions Service (http://www.ucas.ac.uk/) show that, whereas 9192 “home” (United Kingdom) entrants applied to medical school in October 1995, five years later this number had dropped by 12%, to 8108. Medical schools expanded, and in 2000 the number of home entrants was 5229 compared with 4361 in 1995, a rise of 20%. The most important statistic underlying selection is the selection ratio1—the number of applicants for each place at medical school—and it fell from 2.11 in 1995 to 1.55 in 2000.

The falling selection ratio inevitably concerned the Department of Health. Medical education in the United Kingdom is currently expanding. Five new medical schools will have opened by 2005, and 6873 home entrants will start medical school in the United Kingdom,2 a 31% increase over 2000 and a 58% increase over 1995. The worry …
Smooth Muscle α-Actin Gene Requires Two E-Boxes for Proper Expression In Vivo and Is a Target of Class I Basic Helix-Loop-Helix Proteins
Authors: Meena S. Kumar, Jennifer A. Hendrix, A. Daniel Johnson, Gary K. Owens
Journal: Circulation Research (2003)

Changes in the differentiated state of smooth muscle cells (SMCs) play a key role in vascular diseases, yet the mechanisms controlling SMC differentiation are still largely undefined. We addressed the role of basic helix-loop-helix (bHLH) proteins in SMC differentiation by first determining the role of two E-box (CAnnTG) motifs, binding sites for bHLH proteins, in the transcriptional regulation of the SMC differentiation marker gene, smooth muscle α-actin (SM α-actin), in vivo. Mutation of one or both E-boxes significantly reduced the expression of a −2560- to 2784-bp SM α-actin promoter/LacZ reporter gene in vivo in transgenic mice. We then determined the potential role of class I bHLH proteins, E12, E47, HEB, and E2-2, in SM α-actin regulation. In cotransfection experiments, E12, HEB, and E2-2 activated the SM α-actin promoter. Activation by HEB and E2-2 was synergistic with serum response factor. Additionally, the dominant-negative/inhibitory HLH proteins, Id2, Id3, and Twist, inhibited both the E12 and serum response factor–induced activations of the SM α-actin promoter. Finally, we demonstrated that E2A proteins (E12/E47) specifically bound the E-box–containing region of the SM α-actin promoter in vivo in the context of intact chromatin in SMCs. Taken together, these results provide the first evidence of E-box–dependent regulation of a SMC differentiation marker gene in vivo in transgenic mice. Moreover, they demonstrate a potential role for class I bHLH factors and their inhibitors, Id and Twist, in SM α-actin regulation and suggest that these factors may play an important role in control of SMC differentiation and phenotypic modulation.
Acute episodic hemolysis in the African black rhinoceros as an analogue of human glucose‐6‐phosphate dehydrogenase deficiency
Authors: Donald E. Paglia
Journal: American Journal of Hematology (1993)

Abstract Sudden episodes of massive hemolysis have become the most common cause of death among captive black rhinoceroses, and there is evidence that they occur in the wild as well. We have observed radically unique enzyme and metabolite profiles in normal rhinoceros erythrocytes compared to humans and other mammals, including marked deficiencies of intracellular adenosine triphosphate (ATP), catalase, adenosine deaminase, and other enzymes involved in glycolysis, glutathione cycling, and nucleotide metabolism. Minimal concentrations of ATP appear to impair effective acceleration of hexosemono‐phosphate shunt activity in response to oxidants by restricting substrate generation at the hexokinase step. Antioxidant defenses are further compromised by catalase deficiency, which may be a general characteristic of rhinoceros erythrocytes, perhaps related to the common occurrence of severe mucocutaneous ulcerative disease. It is proposed that erythrocyte ATP deficiency in rhinoceroses may be an evolutionary adaptation conferring selective advantage against common hemic parasites, comparable to the role of human glucose‐6‐phosphate dehydrogenase (G‐6‐PD) deficiency in falciparum malaria. © 1993 Wiley‐Liss, Inc.
Evaluation of novel molecular markers for the detection of breast cancer cells in peripheral blood
Authors: Jin Kyung Lee, Young-Joon Hong, Yun Hee Kim, Yoon Hwan Chang, Seok-Il Hong, Woo Chul Noh, Hye Jin Kang
Journal: Clinical Cancer Research (2006)

A37  Introduction : Molecular detection of breast cancer cells in peripheral blood can be useful for staging, optimizing individualized treatment and early detection of recurrence. Cytokeratin 19 (CK19) has been known as a marker for epithelial cells. BU101 and BS106 are breast-specific markers recently reported by researchers in Duke University and Abbott Laboratories. The aim of this study is to evaluate the clinical utility of these three markers (CK19, BU101, BS106) for the detection of occult breast cancer cells in peripheral blood.Method : 3mL of EDTA-anticoagulated blood from 34 breast cancer patients and 18 non-cancerous women were used. We separated mononuclear cells from whole blood by Ficoll-Hypaque gradient centrifugation, and extracted total RNA (Magtration System 6GC, Precision System Science Co., Ltd. Japan). Quantitative real-time RT-PCR assays were performed with 4 molecular beacon probes (CK19, BU101, BS106 and beta2 microglobulin). We used SK-BR3 cell line to construct a standard curve for each marker.Result : Out of the 34 breast cancer patients assayed, 9(26.5%) had detectable CK19 expression and 6(17.6%) had BS106. One breast cancer patient who had both CK19 and BS106 expression has revealed to have bone marrow metastasis. BU101 expression was not detected in peripheral bloods of breast cancer patients assayed in this study. Out of 18 non-cancerous women, CK19, BU101 and BS106 were detected in 3(16.7%), 1(5.6%) and 6(33.3%) respectively. CK19+BS106 and BU101+BS106 expressions were detectable in 1 specimen each. No breast cancer or non-cancerous specimen showed detectable expression in all three markers.Conclusion : Although BS106 is expressed considerably in peripheral blood of non-cancerous women, a combination of three markers (CK19, BU101 and BS106) seems to have a potential utility in clinical settings to detect occult breast caner cells. Further evaluation with a large number of specimens and long-term follow up would be needed.
Neoadjuvant Imatinib in Advanced Primary or Locally Recurrent Dermatofibrosarcoma Protuberans: A Multicenter Phase II DeCOG Trial with Long-term Follow-up
Authors: Selma Ugurel, Thomas Mentzel, Jochen Utikal, Peter Helmbold, Peter Mohr, Claudia Pföhler, Meinhard Schiller, Axel Hauschild, Rüdiger Hein, Eckhardt Kämpgen, Ivonne Kellner, Martin Leverkus, Jürgen C. Becker, Philip Ströbel, Dirk Schadendorf
Journal: Clinical Cancer Research (2013)

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor. COL1A1-PDGFB gene fusion is frequent in DFSP, rendering tumor cell proliferation and survival dependent on PDGFRβ (platelet-derived growth factor receptor β) signaling. This trial investigated imatinib as neoadjuvant treatment of DFSP, including long-term follow-up.The primary endpoint of this multicenter phase II trial was response; secondary endpoints were safety, tumor relapse, and response biomarkers. Patients with advanced primary or locally recurrent DFSP and measurable disease by RECIST (response evaluation criteria in solid tumors) were eligible and received imatinib 600 mg/d until definitive surgery with histopathologic proof of tumor-free margins.Sixteen patients received imatinib, and 14 patients were evaluable for all endpoints. Median treatment duration was 3.1 months; median tumor shrinkage was 31.5%. Best overall response was 7.1% complete response (CR), 50.0% partial response (PR), 35.7% stable disease, and 7.1% progressive disease (PD). Toxicity was moderate with 25.0% grade 3 and 4 events. During a median follow-up of 6.4 years, one patient developed secondary resistance to imatinib but responded to second-line sunitinib. This patient also presented local recurrence, distant metastasis, and death from DFSP. Exploratory analysis showed that response to imatinib was associated with decreased tumor cellularity and formation of strong hyalinic fibrosis. Weak PDGFRB phosphorylation and pigmented-type DFSP were associated with nonresponse. Additional to PDGFRB, the kinases EGFR and insulin receptor were found activated in a high percentage of DFSPs.The neoadjuvant use of imatinib 600 mg/d in DFSP is efficacious and well tolerated. Long-term follow-up results do not definitely support smaller surgical margins after successful imatinib pretreatment, and presume that secondary resistance to imatinib might promote accelerated disease progression.
Humoral immune response to vaccines in patients with rheumatoid arthritis treated with tocilizumab: results of a randomised controlled trial (VISARA)
Authors: Clifton O Bingham, Warren Rizzo, Alan Kivitz, Azra Hassanali, Ruchi Upmanyu, Micki Klearman
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To evaluate the effect of tocilizumab (TCZ), an interleukin 6 receptor inhibitor, on humoral immune responses to immunisations in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Patients with RA with inadequate response/intolerance to one or more anti-tumour necrosis factor-α agents were randomly assigned (2:1) to TCZ 8 mg/kg intravenously every 4 weeks plus methotrexate (MTX) or MTX alone up until week 8. Serum was collected before vaccination at week 3, antibody titres were evaluated at week 8, and then all patients received TCZ+MTX through week 20. End points included proportion of patients responding to ≥6/12 pneumococcal polysaccharide vaccine (PPV23) serotypes (primary) and proportions responding to tetanus toxoid vaccine (TTV; secondary) at week 8. <h3>Results</h3> 91 patients were randomised. At week 8, 60.0% of TCZ+MTX and 70.8% of MTX patients responded to ≥6/12 PPV23 serotypes, with insufficient evidence for any difference in treatments (10.8% (95% CI −33.7 to 12.0)), and 42.0% and 39.1%, respectively, responded to TTV. Two of three TCZ+MTX patients with non-protective baseline TTV antibody titres achieved protective levels by week 8. The safety profile of TCZ was consistent with previous reports. <h3>Conclusions</h3> Short-term TCZ treatment does not significantly attenuate humoral responses to PPV23 or TTV. To maximise vaccine response, patients should be up to date with immunisations before starting TCZ treatment. <h3>ClinicalTrials.gov identifier</h3> NCT01163747.
Collusion in doctor-patient communication about imminent death: an ethnographic study
Authors: A.-M. The, T. Hak, G. Koeter, G. van der Wal
Journal: BMJ (2000)

To discover and explore the factors that result in "false optimism about recovery" observed in patients with small cell lung cancer.A qualitative observational (ethnographic) study in two stages over four years.Lung diseases ward and outpatient clinic in university hospital in the Netherlands.35 patients with small cell lung cancer."False optimism about recovery" usually developed during the (first) course of chemotherapy and was most prevalent when the cancer could no longer be seen in the x ray pictures. This optimism tended to vanish when the tumour recurred, but it could develop again, though to a lesser extent, during further courses of chemotherapy. Patients gradually found out the facts about their poor prognosis, partly because of physical deterioration and partly through contact with fellow patients who were in a more advanced stage of the illness and were dying. "False optimism about recovery" was the result an association between doctors' activism and patients' adherence to the treatment calendar and to the "recovery plot," which allowed them not to acknowledge explicitly what they should and could know. The doctor did and did not want to pronounce a "death sentence" and the patient did and did not want to hear it.Solutions to the problem of collusion between doctor and patient require an active, patient oriented approach from the doctor. Perhaps solutions have to be found outside the doctor-patient relationship itself - for example, by involving "treatment brokers."
Defining the Group A Streptococcal Toxic Shock Syndrome
Authors: Robert F. Breiman
Journal: JAMA (1993)

GROUP A streptococcus (<i>Streptococcus pyogenes</i>) may cause a variety of illnesses ranging from very common, usually clinically mild conditions such as pharyngitis and impetigo to less common severe infections including septicemia and pneumonia. In 1987, Cone et al<sup>1</sup>described two patients with severe group A streptococcal infections having clinical features similar to the staphylococcal toxic shock syndrome. This syndrome, designated the "streptococcal toxic shock—like syndrome" or the "toxic streptococcal syndrome,"<sup>2</sup>was further characterized by Stevens et al<sup>3</sup>in a series of 20 patients. Most patients included in this series were less than 50 years old and otherwise healthy. All had invasive group A streptococcal infections characterized by signs including shock, multi—organ system involvement, and rapidly progressive, destructive soft-tissue infection (necrotizing fasciitis). The case-fatality rate was 30% even though most patients received appropriate antimicrobial therapy, supportive care, and, where necessary, surgical débridement. Ten available isolates were serotyped and
Off-Pump Coronary Artery Bypass Grafting Reduces Mortality and Stroke in Patients With Atheromatous Aortas: A Case Control Study
Authors: Ram Sharony, Costas S. Bizekis, Marc Kanchuger, Aubrey C. Galloway, Paul C. Saunders, Robert Applebaum, Charles F. Schwartz, Greg H. Ribakove, Alfred T. Culliford, F. Gregory Baumann, Itzhak Kronzon, Stephen B. Colvin, Eugene A. Grossi
Journal: Circulation (2003)

Background— Patients with severe atheromatous aortic disease (AAD) who undergo coronary artery bypass (CABG) have an increased risk of death and stroke. We hypothesized that in these high risk patients, off-pump coronary artery bypass (OPCAB) technique is associated with lower morbidity and mortality. Methods and Results— Between June 1993 and January 2002, 5737 patients undergoing CABG had routine intra-operative TEE with 913 (15.9%) found to have severe AAD in the aortic arch or ascending aorta. Of these, 211 patients who underwent OPCAB were matched with 211 on-pump CABG patients by age, ejection fraction, history of stroke, cerebrovascular disease, diabetes, renal disease, nonelective operation, and previous cardiac surgery. Hospital mortality was 11.4% (24/211) for on-pump CABG and 3.8% (8/211) for OPCAB ( P =0.003). Multivariate analysis revealed that increased mortality was associated with on-pump CABG ( P =0.001), acute MI ( P =0.03), number of grafts ( P =0.01), age ( P =0.01), history of stroke or cerebrovascular disease ( P =0.04), CHF ( P =0.02), and peripheral vascular disease ( P =0.03). Multivariate analysis showed that OPCAB technique was associated with decreased stroke ( P =0.05). Freedom from any complication was 78.7% for on-pump CABG and 91.9% for OPCAB ( P &lt;0.001). At 36 month follow-up multivariate analysis revealed that increased mortality was associated with age ( P =0.001), previous MI ( P =0.03), and renal disease ( P =0.04), whereas increased survival was associated with increased number of grafts ( P =0.001) and OPCAB ( P =0.01). Conclusions— OPCAB surgery in patients with severe AAD is associated with lower risk of death, stroke and complications and improved mid-term survival. Routine intra-operative TEE allows identification of these patients and directs choice of appropriate surgical technique.
Regression of Inflammation in Atherosclerosis by the LXR Agonist R211945
Authors: Esad Vucic, Claudia Calcagno, Stephen D. Dickson, James H.F. Rudd, Katsumi Hayashi, Jan Bucerius, Erin Moshier, Jessica S. Mounessa, Michelle Roytman, Matthew J. Moon, James Lin, Sarayu Ramachandran, Tatsuo Tanimoto, Karen Brown, Masakatsu Kotsuma, Sotirios Tsimikas, Edward A. Fisher, Klaas Nicolay, Valentin Fuster, Zahi A. Fayad
Journal: JACC. Cardiovascular imaging (2012)