tbuckley/cabot-search huggingface dataset:
Urinary Excretion of Angiotensin Converting Enzyme in NIDDM Patients With Nephropathy
Authors: Hiroyuki Hosojima, Eiji Miyauchi, Shinpei Morimoto
Journal: Diabetes Care (1989)

Twenty-four-hour urinary excretion of angiotensin-converting enzyme (ACE) was investigated in relation to that of albumin and beta 2-microglobulin (beta 2M) in 25 non-insulin-dependent diabetes mellitus (NIDDM) patients without nephropathy, 13 NIDDM patients with incipient nephropathy, 18 NIDDM patients with overt nephropathy, and 14 nondiabetic subjects. NIDDM patients without nephropathy and nondiabetic subjects were similar in albumin, beta 2M, and ACE excretion. NIDDM patients with incipient nephropathy had elevated albumin excretion (P less than .01) and similar beta 2M and ACE excretion compared with nondiabetic subjects. On the other hand, NIDDM patients with overt nephropathy had elevated albumin, beta 2M, and ACE excretion compared with nondiabetic subjects (P less than .01). In all NIDDM patients studied, a positive correlation was found between ACE excretion and albumin excretion (r = 0.76, P less than .001) or beta 2M excretion (r = 0.52, P less than .01). These data suggest that elevated ACE excretion in NIDDM patients with overt nephropathy may be reflective of renal tubular damage.
Surviving ischemia: adaptive responses mediated by hypoxia-inducible factor 1
Authors: Gregg L. Semenza
Journal: Journal of Clinical Investigation (2000)

Tissue responses to ischemiaWhile the other Perspectives in this series provide readers with state-of-the-art overviews of responses to ischemia on an organ-by-organ basis, I focus here on a single transcription factor, hypoxia-inducible factor 1 (HIF-1), and its role in the physiologic responses to hypoxia and ischemia.Whether in the brain, heart, kidneys, lungs, or muscle, HIF-1 is essential for ischemiainduced angiogenesis, as described by Isner (this Perspective series, ref. 1), and it may also be a critical mediator of late-phase preconditioning, as described by Williams and Benjamin (this Perspective series, ref.2).For these reasons, HIF-1 and the genes under its control may represent novel therapeutic targets for ameliorating the effects of ischemia in a variety of clinical settings.
Cough and tachypnoea in a toddler
Authors: S. Muthusamy, H. C Pandya, D. Luyt
Journal: Journal of the Royal Society of Medicine (2003)

In part 1 we reported how a 17-month-old girl became rapidly ill with cough, pyrexia and respiratory distress. A chest X-ray showed air—fluid cavities in the right hemithorax. Ventilation became necessary and a post-intubation chest radiograph unexpectedly showed an increase in the size and number of cavities in the right hemithorax (Figure 1).​).



Figure 1

Pre-intubation chest radiograph





Figure 3

CT scan of chest after exploratory surgery. This cross-section is a slice at a level below the tracheal bifurcation. Several cavities can be seen (asterisks) in the right middle lobe. There is also collapse and consolidation of middle lobe segments ...



The child was transferred to our paediatric intensive-care unit where she was reviewed by a consultant paediatric intensivist and a consultant paediatric surgeon. Her chest radiographs were reviewed by a consultant paediatric radiologist. All the clinicians agreed that her clinical course and findings were consistent with a diagnosis of a late-presenting congenital right-sided diaphragmatic hernia. However, on exploratory laparotomy the diaphragm was found to be intact. A CT scan then revealed multiple right-sided pulmonary abscesses (Figure 2). Next day she underwent a right middle lobe excision, from which she recovered without incident. No organisms were isolated either from the excised tissue or from blood cultures. The pathologist found no evidence of a bronchopleural fistula.



Figure 2

Post-intubation chest radiograph
BLOOD PLASMA PROTEINS AS INFLUENCED BY INTRAVENOUS INJECTION OF GUM ACACIA
Authors: Charles L. Yuile, Ralph E. Knutti
Journal: The Journal of Experimental Medicine (1939)

By repeated weekly intravenous injections of gum acacia solution in dogs over periods of 4 to 5 months, it has been possible to maintain plasma protein concentration and total circulating protein at very low levels. If sufficient numbers of such injections are given and then discontinued, plasma protein concentration will remain below the normal limits for several more months. Acacia remains in the blood during this time. Reduction of fibrinogen concentration in such animals is out of proportion to and more marked than the changes in plasma protein concentration. This would indicate interference with liver function. Plasma volume when determined at 7 day intervals during injection periods at first diminishes, then rises 20 to 25 per cent above basal levels. The total blood volume does not show such marked changes because of a decrease in red cell volume. Globulins are reduced to a greater extent than albumin after a single injection of gum acacia, although both albumin and the globulins diminish. This cannot be accounted for by a decrease in fibrinogen alone. After 14 to 16 weekly injections, both albumin and globulins are more profoundly reduced. During injection periods in such animals, it has not been possible to control quantitatively the dietary intake, a complication which has made it difficult to ascertain the effect of various protein diets upon the protein-acacia balance. The changes described, however, have taken place regardless of various types of animal protein diets. Following periods of injection, in spite of very low plasma protein concentration and high acacia concentration in the blood, most of the dogs eat well and therefore they can be used during this period for controlled dietary experiments which may be of value in investigating the mechanism of the production and function of the plasma proteins.
The Discovery of the Germ
Authors: B. Twisselmann
Journal: BMJ (2003)

John Waller Icon Books, £9.99, pp 198 ISBN 1840463732 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> John Waller offers an in-depth history of what he calls the "extraordinary, albeit bloodless, scientific revolution" that took place between 1880 and 1900. This was a time when medicine underwent perhaps its biggest transformation and the way we think about disease was changed forever. The story he tells reads like a thriller on more than one occasion. He fills in the background from 500 bc and explains the prevailing theories … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Efficacy of Peanut and Soybean-Specific IgE Probability Curves Derived from Two Different Serologic Methods (3g and immunoCAP)
Authors: Kiyotake Ogura, Sakura Sato, Kazuko Kutsuwada, Yasunori Sato, Motohiro Ebisawa
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract 917: AZD2014, a dual mTORC1 and mTORC2 inhibitor is differentiated from allosteric inhibitors of mTORC1 in ER+ breast cancer
Authors: Sylvie M. Guichard, Zoe Howard, Dan Heathcote, Mark Roth, Gareth Hughes, Jon Curwen, James Yates, Armelle Logie, Sarah Holt, Christine M. Chresta, Barry R. Davies, Karine Malagu, Marc Hummersone, Sarah L. Pass, Stephen Green, Martin Pass
Journal: Cancer Research (2012)

Abstract The mammalian target of rapamycin (mTOR) is a major sensor of nutrients and energy and is part of two multiprotein complexes mTORC1 and mTORC2. mTOR activation is widely reported in cancer and is associated with poor prognosis and resistance to standard of care treatment. Allosteric inhibitors of mTOR such as rapamycin partially inhibit mTORC1 and do not inhibit mTORC2. AZD2014 is a close analogue of AZD8055 and a selective inhibitor of mTOR kinase. AZD2014 has greater inhibitory activity against mTORC1 compared to rapamycin: AZD2014 decreases p4EBP1 Thr37/46, inhibits the translation initiation complex and decreases overall protein synthesis while rapamycin has no effect. AZD2014 also inhibits the mTORC2 biomarkers pAKTSer473 and pNDRG1Thr346. AZD2014 has broad antiproliferative activity across multiple tumour cell lines. In particular, AZD2014 induces growth inhibition and cell death in breast cancer cell lines, including ER+ cell lines with acquired resistance to hormone therapy. In vitro, the potency of AZD2014 is ∼ 5-fold lower compared to AZD8055. However, AZD2014 has improved pharmacokinetics compared to AZD8055. In vivo, AZD2014 induces tumour growth inhibition against several xenograft models including a human primary explant model of ER+ breast cancer refractory to tamoxifen. The antitumour activity is associated with modulation of both mTORC1 and mTORC2 substrates. Overall, AZD2014 is a potent mTOR kinase inhibitor with an in vitro profile comparable to AZD8055 but with improved pharmacokinetic properties over AZD8055. AZD2014 is currently in phase 1 clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 917. doi:1538-7445.AM2012-917
Robert Cruickshank (Jim) Burgess Evan Lewis Butler Donald John Campbell Susanta Kumar Gupta Andrew Henry Garmany Love Jane Ann Marks (nee Blythe) Adele Nye (nee Fischbacher) Gordon Jackson Rees Robert MacDonald Shaw Thambipillai Sivalingham
Authors: S. L Morrison
Journal: BMJ (2001)

Jim joined the Malayan Medical Service soon after qualification and specialised in the nutritional problems of the rural population; his field studies of diet and beri-beri explained its unusual pattern of rising with prosperity (eating milled rice) and falling when the economy was depressed (eating hand-pounded rice).After a spell in the Institute for Medical Research in Kuala Lumpur, when war came he joined the army as nutrition officer for Malaya Command.Imprisoned in Changi in Singapore, he played a large part in developing ways of combating the many deficiency diseases prevalent among the malnourished prisoners, including helping to set up a "factory" to produce an extract of grass to prevent and treat riboflavin deficiency.After the war he joined WHO, where his knowledge of, and sympathy with, rural people in developing countries ensured that his proposals for action were realistic and practical.When he retired in 1962, he joined the department of public health at Edinburgh, staying until 1967.He enjoyed hill walking, and played golf until his 90s.Predeceased by his wife, Anne, he leaves two children, and three grandchildren.[
Peptide Amphiphile Nanoparticles Enhance the Immune Response Against a CpG‐Adjuvanted Influenza Antigen
Authors: Harshal Zope, Christophe Barnier Quer, Paul H. H. Bomans, Nico A. J. M. Sommerdijk, Alexander Kros, Wim Jiskoot
Journal: Advanced Healthcare Materials (2013)

Cationic peptide amphiphile nanoparticles are employed for co-delivery of immune modulator CpG and antigen. This results in better targeting to the antigen presenting cells and eliciting strong Th1 response, which is effective against the intracellular pathogens. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Time-dependent response of coronary flow to prolonged adenosine infusion: doubling of peak reactive hyperaemic flow
Authors: A. L'ABBATE, P. CAMICI, M. G TRIVELLA, G. PELOSI, G. J DAVIES, A. M BALLESTRA, L. TADDEI
Journal: Cardiovascular Research (1981)

In 11 anaesthetised, open chest dogs the time course and degree of the coronary vasodilating response to intracoronary adenosine infusion was assessed. Continuous adenosine infusion, at a rate of 2.5 to 13.5 μmol·min−1, produced rapid (15 to 30 s) vasodilatation of the same degree as that evoked by a 30 s period of ischaemia (reactive peak hyperaemia), a finding reported previously by others. However, continuing the infusion led to further coronary vasodilatation, reaching a maximum 20 to 45 min from the beginning of the infusion and remaining constant for up to 2 h, independently of further increases in the dose. This late response produced, on average, vasodilatation twice as great as that observed during reactive hyperaemia and was not associated with any haemodynamic change or with the opening of arterio-venous shunts. The results: 1) suggest the existence of a double, time-dependent response of coronary receptor(s) to adenosine; 2) demonstrate, in the presence of a prolonged vasodilating stimulus, a possible increase in coronary blood flow to a degree far beyond that of post-ischaemic reactive peak flow, which is generally considered to be the maximal value of coronary blood flow that can be achieved.
GE-09 * TERT PROMOTER MUTATION, IDH MUTATION AND 1p/19q CODELETION DEFINE FIVE GLIOMA MOLECULAR GROUPS WITH SPECIFIC CLINICAL CHARACTERISTICS AND GERMLINE VARIANT ASSOCIATIONS
Authors: J. Eckel-Passow, D. Lachance, K. Walsh, P. Decker, H. Sicotte, M. Pekmezci, A. Molinaro, T. Rice, M. Kosel, I. Smirnov, G. Sarkar, A. Caron, T. Kollmeyer, C. Giannini, J. Huse, T. Tihan, J. Wiemels, J. Wiencke, M. Wrensch, R. Jenkins
Journal: Neuro-Oncology (2014)

Defining homogenous etiologic and clinical subgroups of infiltrative glioma by grade and histology has been challenging. We hypothesized that TERT promoter mutation, IDH mutation and 1p/19q codeletion in grade II-IV gliomas will generate clinically-homogeneous groups that are enriched for other acquired genetic alterations and specific germline associations. To test this hypothesis we assessed 1087 gliomas from the Mayo Clinic, UCSF Adult Glioma Study, and TCGA and compared other acquired alterations and patient characteristics among five primary molecular groups: triple-positive (TERT promoter mutated, IDH mutated, and 1p/19q codeleted), TERT and IDH mutant, IDH mutant only, triple-negative, and TERT mutant only. Using 11590 controls, we also assessed associations of these groups with known germline variants. Among grade II-III gliomas 29.2% were triple-positive, 5% TERT and IDH mutant, 44.6% IDH mutant only, 6.6% triple-negative, 10% TERT mutant only, and 4.5% other. For grade IV gliomas 0.2% were triple-positive, 2.4% TERT and IDH mutant, 6.8% IDH mutant only, 17.1% triple-negative, and 73.5% TERT mutant only. Within the five groups other acquired alterations were more homogeneous than when the cases were subdivided by grade or histology. Age at diagnosis was youngest for IDH mutant only (35 years) and oldest for TERT mutant only gliomas (60 years). Overall survival differed across groups both within grade II-III and within grade IV gliomas. There were specific associations between glioma molecular groups and germline variants. These association results were similar across the three studies. We conclude that gliomas can be classified into clinically-relevant groups based on three tumor markers. This classification scheme is appealing due to its simplicity, reproducibility, and cost-efficiency. These molecular groups have different ages at diagnosis, overall survival and germline associations implying distinct mechanisms of pathogenesis, aggressiveness, and response to therapy. These groups can enhance histologic diagnosis and permit more precisely targeted patient management.
UK government must stop making heroic promises, report says
Authors: K. Burke
Journal: BMJ (2002)

<h3>Abstract</h3> Although new advances in neuroscience allow the study of vocal communication in awake animals, substantial progress in the processing of vocalizations has been made from brains of anaesthetized preparations. Thus, understanding how anaesthetics affect neuronal responses is of paramount importance. Here, we used electrophysiological recordings and computational modelling to study how the auditory cortex of bats responds to vocalizations under anaesthesia and in wakefulness. We found that multifunctional neurons that process echolocation and communication sounds were affected by ketamine anaesthesia in a manner that could not be predicted by known anaesthetic effects. In wakefulness, acoustic contexts (preceding echolocation or communication sequences) led to stimulus-specific suppression of lagging sounds, accentuating neuronal responses to sound transitions. However, under anaesthesia, communication contexts (but not echolocation) led to a global suppression of responses to lagging sounds. Such asymmetric effect was dependent on the frequency composition of the contexts and not on their temporal patterns. We constructed a neuron model that could replicate the data obtained <i>in vivo</i>. In the model, anaesthesia modulates spiking activity in a channel-specific manner, decreasing responses of cortical inputs tuned to high-frequency sounds and increasing adaptation in the respective cortical synapses. Combined, our findings obtained <i>in vivo</i> and <i>in silico</i> reveal that ketamine anaesthesia does not reduce uniformly the neurons’ responsiveness to low and high frequency sounds. This effect depends on combined mechanisms that unbalance cortical inputs and ultimately affect how auditory cortex neurons respond to natural sounds in anaesthetized preparations.
Surgical Nutrition: The Fourth Coming
Authors: James C. Stevens
Journal: JAMA (1978)

<h3>To the Editor.—</h3> The advent of intensive nutritional support for nutritionally depleted preoperative and postoperative patients might well prove to be the "fourth coming" of a major advance in the care of surgical patients in the past 150 years. The "first coming" was the beginnings of surgical anesthesia exemplified by Crawford W. Long, MD, who in 1847 began using ether for obstetrical patients (including his wife). In 1867 Joseph Lister, MB, BS, recognized the importance of wound infection and proposed the antiseptic principle, thus providing a "second coming." The "third coming" was the antibiotic era, introduced by Sir Alexander Fleming in 1928 with the demonstration of the bactericidal effects of penicillin. In 1968 Stanley Dudrick, MD, and others<sup>1</sup>began to advocate total parenteral nutrition for patients with poorly functional gastrointestinal tracts and catabolic disease processes. He demonstrated accelerated healing in processes that had previously carried poor prognosis. Since that
Thyroid Carcinoma Ten Years After Sodium Iodide I131 Treatment
Authors: Gerald Burke
Journal: JAMA (1967)

There was coexistence of thyroid carcinoma and hyperthyroidism in a 37-year-old woman previously (apparently successfully) treated with sodium iodide I 131 for thyrotoxicosis. There was an uncommon sequence of events in this case and a possible relationship between<sup>131</sup>I therapy and subsequent development of thyroid carcinoma existed. Since the reported frequency of thyroid carcinoma following<sup>131</sup>I therapy in the adult is well within the range of statistical coincidence, no basis for a cause and effect relationship presently exists.
Benefits of early tracheotomy: underpowered or overestimated?
Authors: Denise Petra Veelo, Ognjen Gajic, Marcus J. Schultz
Journal: Intensive Care Medicine (2008)

To the editor: With interest we read the recent article from Blot et al. [1] in which they compared 28-day mortality of patients with early tracheotomy against those with prolonged intubation in a prospective randomized unblinded study. This trial is the first multi-centered randomized study on this topic and we would like to complement the investigators for their effort in achieving this trial. The study does not demonstrate any major benefit of early tracheotomy in a general population of intensive care unit-patients, but hints at putative comfort benefits. As the authors admit their study is severely underpowered. Indeed, the study was prematurely stopped because after about 2 years only 123 patients had been included. Of note, only 10–20% of the patients assessed for eligibility were actually included. One of the major reasons for noninclusion was the difficulty in anticipating mechanical ventilation lasting [7 days, one of the inclusion criteria of the study. We wonder how many patients in the prolonged intubation group finally reached 7 days of mechanical ventilation after randomization. If a substantial number of patients were extubated before that time the patients enrolled may not represent the population of interest (those at high risk of prolonged mechanical ventilation). Unfortunately, the authors did not use explicit criteria to predict prolonged mechanical ventilation (such as the presence of shock and multiorgan failure, oxygenation index, high APACHE II scores [2–4]). Another reason for non-inclusion was difficulties in organizing early tracheotomy. How long patients had to await a tracheotomy in the early tracheotomy group in this study? If this was ‘‘too’’ long the potential benefits may have been diluted? Two secondary endpoints were sedation requirements during the first 28 days and self-reported patient comfort. Sedation requirements were not different between the two study groups, which is in part in line with recent data from our group [5] but opposite to results from others [6]. Unfortunately, however, data on cumulative dose were not given. Although the number of sedation-free days was not different, the administered dose may have been different between the two groups. This could potentially explain the significant difference in self-reported comfort in favor of early tracheotomy.
Association Study of the let-7 miRNA-Complementary Site Variant in the 3′ Untranslated Region of the<i>KRAS</i>Gene in Stage III Colon Cancer (NCCTG N0147 Clinical Trial)
Authors: Dan Sha, Adam M. Lee, Qian Shi, Steven R. Alberts, Daniel J. Sargent, Frank A. Sinicrope, Robert B. Diasio
Journal: Clinical Cancer Research (2014)

Abstract Purpose: A let-7 microRNA-complementary site (LCS6) polymorphism in the 3′ untranslated region of the KRAS gene has been shown to disrupt let-7 binding and upregulate KRAS expression. We evaluated the LCS6 genotype and its association with KRAS mutation status, clinicopathologic features, and disease-free survival (DFS) in patients with stage III colon cancer who enrolled in a phase III clinical trial (NCCTG N0147). Experimental Design: The LCS6 genotype was assayed by real-time PCR in DNA extracted from whole blood (n = 2,834) and compared with paired tumor tissue (n = 977). χ2 and two-sample t tests were used to compare baseline factors and KRAS mutation status between patients defined by LCS6 variant status. Log-rank tests and multivariate Cox models assessed associations between LCS6 status and DFS, respectively. Results: We identified 432 (15.2%) blood samples and 143 (14.6%) tumor samples heterozygous or homozygous for the LCS6 G-allele, and 2,402 of 2,834 (84.8%) blood samples and 834 of 977 (85.4%) tumor samples homozygous for the LCS6 T-allele. Genotype results were highly concordant (99.8%) in cases with paired blood and tumor tissue (n = 977). G-allele carriers were significantly more frequent in Caucasians versus other races (χ2 test, P &amp;lt; 0.0001). The LCS6 genotype was not associated with KRAS mutation status, clinicopathologic features (all P &amp;gt; 0.2), or DFS (log-rank P = 0.49; HR, 0.929; 95% confidence interval, 0.76–1.14), even after combining LCS6 genotype with KRAS mutation status. Conclusions: In the largest association study investigating the LCS6 polymorphism in colon cancers, the germline LCS6 genotype was not associated with KRAS mutation status or with clinical outcome in patients with stage III tumors. Clin Cancer Res; 20(12); 3319–27. ©2014 AACR.