tbuckley/cabot-search huggingface dataset:
A Trial of Treatment for Acute Otorrhea in Children with Tympanostomy Tubes
Authors: Thijs M.A. van Dongen, Geert J.M.G. van der Heijden, Roderick P. Venekamp, Maroeska M. Rovers, Anne G.M. Schilder
Journal: New England Journal of Medicine (2014)

Recent guidance for the management of acute otorrhea in children with tympanostomy tubes is based on limited evidence from trials comparing oral antibiotic agents with topical antibiotics.In this open-label, pragmatic trial, we randomly assigned 230 children, 1 to 10 years of age, who had acute tympanostomy-tube otorrhea to receive hydrocortisone-bacitracin-colistin eardrops (76 children) or oral amoxicillin-clavulanate suspension (77) or to undergo initial observation (77). The primary outcome was the presence of otorrhea, as assessed otoscopically, 2 weeks after study-group assignment. Secondary outcomes were the duration of the initial otorrhea episode, the total number of days of otorrhea and the number of otorrhea recurrences during 6 months of follow-up, quality of life, complications, and treatment-related adverse events.Antibiotic-glucocorticoid eardrops were superior to oral antibiotics and initial observation for all outcomes. At 2 weeks, 5% of children treated with antibiotic-glucocorticoid eardrops had otorrhea, as compared with 44% of those treated with oral antibiotics (risk difference, -39 percentage points; 95% confidence interval [CI], -51 to -26) and 55% of those treated with initial observation (risk difference, -49 percentage points; 95% CI, -62 to -37). The median duration of the initial episode of otorrhea was 4 days for children treated with antibiotic-glucocorticoid eardrops versus 5 days for those treated with oral antibiotics (P<0.001) and 12 days for those who were assigned to initial observation (P<0.001). Treatment-related adverse events were mild, and no complications of otitis media, including local cellulitis, perichondritis, mastoiditis, and intracranial complications, were reported at 2 weeks.Antibiotic-glucocorticoid eardrops were more effective than oral antibiotics and initial observation in children with tympanostomy tubes who had uncomplicated acute otorrhea. (Funded by the Netherlands Organization for Health Research and Development; Netherlands Trial Register number, NTR1481.).
A Single Strain of Clostridium butyricum Induces Intestinal IL-10-Producing Macrophages to Suppress Acute Experimental Colitis in Mice
Authors: Atsushi Hayashi, Toshiro Sato, Nobuhiko Kamada, Yohei Mikami, Katsuyoshi Matsuoka, Tadakazu Hisamatsu, Toshifumi Hibi, Axel Roers, Hideo Yagita, Toshiaki Ohteki, Akihiko Yoshimura, Takanori Kanai
Journal: Cell Host & Microbe (2013)
Enzyme histochemical study of fat absorption in human duodenal mucosa
Authors: H. Monges, A. Chamlian, A. Cougard, B. Mathieu
Journal: Gut (1974)

In seven healthy subjects the activities of various intestinal enzymes were studied using a fasting control peroral biopsy and two other biopsies 15 minutes and 30 minutes after an intestinal infusion of emulsified corn oil. Specific histochemical methods permitted the comparison of the enzymatic activities of the absorptive cells at the top of the villi before and during fat absorption which was demonstrated with a Sudan black stain. FOUR OXYDATIVE ENZYMES WERE MODIFIED AFTER THE CORN OIL INFUSION: NADH2-tetrazolium reductase, NADPH2-tetrazolium reductase, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase. In six cases, the activity of NADH2-tetrazolium reductase was increased. Two of these subjects presented a simultaneous increase of NADPH2-tetrazolium reductase and glucose-6-phosphate dehydrogenase. Two other subjects presented a decrease in lactate dehydrogenase activity.
Botulism and Guanidine
Authors: Marcello Puggiari
Journal: JAMA (1978)

Guanidine hydrochloride was introduced as an adjunct in the treatment of botulism in 1968. It has been reported to be of benefit in 39 cases and of no benefit in 13 cases. No serious side effects have occurred with the short-term therapy required in botulism. Our two cases are similar to earlier cases in that the improvement seen with quanidine therapy is most notable in ocular muscles and least notable in respiratory muscles. Electrophysiological findings again showed an increase in the amplitude of evoked muscle-action potentials after guanidine administration.
PTH-042 Clarifying The Referral Pathways For Patients Diagnosed With Gastrointestinal Cancer: Is The ‘red-flag’ Pathway Working?
Authors: JK Eccles, PM Lynch
Journal: Gut (2014)

<h3>Introduction</h3> The Cancer Access or ‘Red-Flag’ referral pathway was introduced to facilitate appropriate referral between primary and secondary care for cases of suspected cancer. Despite this, many cases of upper and lower gastrointestinal (GI) cancer are diagnosed through ‘routine’ referral grading, emergency presentations, and in the case of colorectal cancers, the bowel cancer screening (BCS) programme. The purpose of this study was to assess the original referral pathway for patients diagnosed with gastrointestinal cancer within our Health Trust and the effects, if any, on patient outcomes. <h3>Methods</h3> We looked at a random sample of clinical notes of 107 patients diagnosed with a GI cancer between April 2011 and December 2012 within our trust (56 patients with lower and 51 patients with upper GI cancer) to determine referral source and grade, whether red-flag criteria were positive, staging and outcomes, whether curative or palliative. <h3>Results</h3> 58 patients (54%) diagnosed with upper or lower GI cancer had been referred to the Trust via GP (with 22% seen initially at clinic and 32% at direct access endoscopy), 5 patients (5%) had been referred to clinic by another physician, 28 patients (26%) attended through casualty, 10 patients were diagnosed through the BCS programme (9%), 5 oesophageal cancers (5%) through Barrett’s surveillance, and 1 colorectal cancer (1%) through polyp surveillance. All 27 lower GI cancer patients initially referred by their GP had ‘red-flag’ symptoms, but only 12 (44%) were referred with an initial ‘red-flag’ grade; similarly, all 31 upper GI cancer patients initially referred by GP had ‘red-flag’ symptoms, but only 15 patients (48%) were initially referred as ‘red-flag’. Of the 51 upper GI cancer patients, 20 underwent curative treatment; 11 such patients were referred from GP (5 of which were originally referred as ‘red-flag’), 3 from another physician, 5 from Barrett’s surveillance and 1 casualty self-presenter. Of the 56 lower GI cancer patients, 33 underwent curative treatment – 17 referred from GP (only 7 originally referred as ‘red-flag’), 6 casualty self-presenters, and all 10 BCS patients (all Dukes’ A-B). Of the 54 palliative cases of either upper or lower GI cancer, only 15 of the 30 patients referred by their GP were referred through the ‘red-flag’ pathway. <h3>Conclusion</h3> All patients diagnosed with a GI cancer that were originally referred from primary care had evidence to satisfy ‘red-flag’ referral, although less than half of these were referred through the ‘red-flag’ pathway. This study highlights the need for ongoing education and reinforcement of the ‘red-flag’ referral criteria. <h3>Disclosure of Interest</h3> None Declared.
Molecular Mechanisms Underlying Oncogenic RET Fusion in Lung Adenocarcinoma
Authors: Tatsuji Mizukami, Kouya Shiraishi, Yoko Shimada, Hideaki Ogiwara, Koji Tsuta, Hitoshi Ichikawa, Hiromi Sakamoto, Mamoru Kato, Tatsuhiro Shibata, Takashi Nakano, Takashi Kohno
Journal: Journal of Thoracic Oncology (2014)

Oncogenic RET fusion, caused by an inversion in chromosome 10, was recently identified as a driver mutation for the development of lung adenocarcinoma (LADC). Nevertheless, the molecular mechanism(s) underlying the rearrangement of the RET locus during lung carcinogenesis are unknown.Genomic segments containing breakpoint junctions for RET fusions were cloned and analyzed by genomic polymerase chain reaction and genome capture sequencing using a next-generation sequencer to identify the mechanisms involved in DNA strand breaks and illegitimate joining of DNA ends. Of the 18 cases studied, 16 were identified by screening 671 LADC cases and two were previously published.Almost all (17 of 18, 94%) of the breakpoints in RET were located within a 2.0-kb region spanning exon 11 to intron 11 and no breakpoint occurred within 4 bp of any other. This suggested that as in papillary thyroid carcinoma, DNA strand breaks formed at nonspecific sites within this region trigger RET fusion. Just over half of the RET fusions in LADC (10 of 18, 56%) were caused by simple reciprocal inversion, and two DNA-repair mechanisms, namely nonhomologous end joining and break-induced replication, were deduced to have contributed to the illegitimate joining of the DNA ends.Oncogenic RET fusion in LADC occurs through multiple pathways and involves the illegitimate repair of DNA strand breaks through mechanisms different from those identified in papillary thyroid carcinoma, where RET fusion also functions as a driver mutation.
The third alternative: Duplication of collopallium in isocortical evolution
Authors: Ann B. Butler
Journal: Behavioral and Brain Sciences (2003)

One hypothesis of isocortical evolution requires tangential migration of glutaminergic neurons. A second requires invasion of collothalamic afferents into the dorsal pallium, a territory that in sauropsids is solely lemnopallial. A third alternative is noted here – duplication of the original collopallial territory. The duplicated region would be formed by radial migration of excitatory neurons and would maintain its collothalamic innervation.
Reduction of Intracellular pH as a Strategy to Enhance the pH-Dependent Cytotoxic Effects of Melphalan for Human Breast Cancer Cells
Authors: Philip Wong, Carol Lee, Ian F. Tannock
Journal: Clinical Cancer Research (2005)

Abstract The microenvironment within solid tumors is slightly acidic, and manipulation of this extracellular acidity to cause intracellular acidification might be used to increase selective antitumor effects of some anticancer drugs. Potential mechanisms include inhibition of repair of DNA damage and inhibition of repopulation of tumor cells between successive courses of chemotherapy. Here, we evaluate the influence of extracellular pH (pHe) and of two agents that lead to intracellular acidification (cariporide and S3705) on toxicity of melphalan for two human breast cancer cell lines (MDA-MB231 and MCF7). Both the total number and number of colony-forming cells were evaluated during and after three sequential weekly drug treatments. Our results indicate the following: (a) Slow or absent repopulation after the first course of treatment that is influenced minimally by pHe. (b) Rapid repopulation after the second course of treatment that may be inhibited at low pHe. (c) Effects of low pHe following treatment with melphalan to increase cell kill. (d) Small effects of incubation in cariporide and S3705 at low pHe to increase the net cell kill after treatment with melphalan. Although these results add to evidence that manipulation of intracellular pH within the acidic environment of solid tumors can influence the effects of chemotherapy, they are too small and inconsistent to warrant clinical evaluation.
Quantitative Assessment of Left Ventricular Diastolic Stiffness in Man
Authors: WILLIAM GROSSMAN, MILTIADIS A. STEFADOUROS, LAMBERT P. MCLAURIN, ELLIS L. ROLETT, DANIEL T. YOUNG
Journal: Circulation (1973)

An approach to the quantitative assessment of left ventricular (LV) diastolic stiffness in man has been developed utilizing strip-chart recordings of simultaneous ultrasonic LV dimensions, LV pressure, and electrocardiogram (ECG). In 23 patients without regional abnormalities of contraction, LV pressure, and LV internal diameter (D = distance between endocardial surfaces of LV posterior wall and septum at the plane of the mitral valve) were determined at the onset (P 1 , D 1 ) and peak (P 2 , D 2 ) of left atrial mechanical systole. In addition, left ventricular volumes, V 1 and V 2 , were calculated from D 1 and D 2 using a regression formula for end-diastolic volume previously determined from biplane angiographic studies. This allowed calculation of ΔP/ΔD and ΔP/ΔV associated with the "a" wave of the LV pressure trace, and these ratios were utilized as measures of LV stiffness late in diastole. Patients with LV hypertrophy by standard ECG criteria had much greater late diastolic stiffness (11 patients, ΔP/ΔD = 6.1 ± 1.1 mm Hg/mm, ΔP/ΔV = 1.0 ± 0.2 mm Hg/cc) than those without LV hypertrophy (12 patients, ΔP/ΔD = 1.8 ± 0.2 mm Hg/mm, ΔP/ΔV = 0.29 ± 0.04 mm Hg/cc, P &lt; 0.001 for each ratio). Comparison of the stiffness ratios showed significant variation among patients with different disease states. Thus, late diastolic stiffness was highest in patients with aortic stenosis (three patients, ΔP/ΔD = 8.9 ± 2.9 mm Hg/mm, ΔP/ΔV = 1.5 ± 0.5 mm Hg/cc), lowest in mitral stenosis (four patients, ΔP/ΔD = 1.5 ± 0.5 mm Hg/mm, ΔP/ΔV = 0.23 ± 0.06 mm Hg/cc), and intermediate in patients with aortic regurgitation (three patients, ΔP/ΔD = 4.8 ± 0.7 mm Hg/mm, ΔP/ΔV = 0.83 ± 0.12 mm Hg/cc) and mitral regurgitation (three patients, ΔP/ΔD = 3.2 ± 0.7 mm Hg/mm, ΔP/ΔV = 0.5 ± 0.1 mm Hg/cc). It is concluded that the quantitative evaluation of LV diastolic stiffness obtained by this approach correlates well with the presence or absence of LV hypertrophy and with the underlying pathophysiology.
QUANTIFICATION OF REST AND EXERCISE SPECT STUDIES WITH BOTH TI-201 THALLOUS CHLORIDE AND Tc-99m ISONITRILE IN NORMAL VOLUNTEERS
Authors: A. C. Civelek, K. Durski, J. Links, P. Cole, J. Turek, H. N. Wagner
Journal: Clinical Nuclear Medicine (1988)

Fifteen normal volunteers underwent both Tl-201 and Tc-99m RP30A SPECT studies during rest and exercise. High resolution images were acquired in 6 degree steps over 360° and images were reconstructed using both 180° and 360° data. Circumferential profiles were generated from long and short axis views using an elliptical ROI around the left ventricle. Both visually and by profile analysis, the 180° images had thinner myocardial walls, sharper edges and a less homogenous distribution of activity than the 360° Images. In the 360° images, but not the 180° images, there was always a focal area of decreased intensity in the inferior wall close to the apex, attributed to attenuation by spine or skeletal muscle. Anterior wall intensity was equal to or less than the inferior wall in the 180° but not the 360° images. A breast attenuation artefact (decreased anterior wall intensity) was more prominent in the 180° than the 360° images. This was more prominent in the thallium-201 than the Tc-99m isonitrile images. With the 180° images, distortion was more prominent than in the 360° images when the left ventricle was long and the apex directed upward: short axis images became elliptical and the walls at the base converged. On the 360° images, the septum intensity was usually equal to that of the lateral wall. These findings were supported by cardiac phantom studies. Taking image resolution, contrast, acquisition and processing times and the occurrence of artefacts into consideration we prefer 180° to 360° acquisition.
Phase II Trial of Sunitinib Maintenance Therapy After Platinum-Based Chemotherapy in Patients with Extensive-Stage Small Cell Lung Cancer
Authors: Bryan J. Schneider, Shirish M. Gadgeel, Nithya Ramnath, Antoinette J. Wozniak, Grace K. Dy, Stephanie Daignault, Gregory P. Kalemkerian
Journal: Journal of Thoracic Oncology (2011)
What Makes Us Run?
Authors: Otto Appenzeller
Journal: New England Journal of Medicine (1981)

When the Persian fleet approached the plains of Marathon in 490 B.C., the Athenian Pheidippides set out for Sparta in quest of military aid. Despite the summer heat, he traveled 240 km of mountain roads in 48 hours at an average speed of 5 km per hour. His oxygen consumption, work output, energy stores, water metabolism, and cardiovascular function were sufficient to sustain him on this journey. His brain was adequately supplied with blood, and upon arrival, he acted diplomatically as a suppliant and orator. Although the Spartans agreed to meet their treaty obligations, they postponed their departure until the . . .
Menopause: The Age of Choice
Authors: Paula A. Munger
Journal: JAMA (1992)

As a second-year medical student, I recently spent time observing in the office of an obstetrician-gynecologist. I was impressed by the frequency with which his menopausal patients mentioned how helpful they had found a book he had given to each of them.<i>Menopause: The Age of Choice</i>is a small paperback written by a nurse practitioner-physician's assistant, Susan Toshach Macfarlan. The book evolved from the author's personal and professional experience with menopause. It is a quite successful attempt to provide answers based on current medical understanding in an age when women are taking a more active role in their own health care. The medical information is presented with enough detail to make the book a handy reference for physicians other than obstetrician-gynecologists, but in language clear enough for the lay reader. The personal style lends a warm, conversational tone. The book focuses on choice based on current medical information and
Physiologically Based Pharmacokinetic Modeling of Persistent OrganicPollutants for Lifetime Exposure Assessment: A New Tool in Breast CancerEpidemiologic Studies
Authors: Marc-André Verner, Michel Charbonneau, Lizbeth López-Carrillo, Sami Haddad
Journal: Environmental Health Perspectives (2008)

Despite experimental evidence, most epidemiologic studies to date have not supported an association between exposure to persistent organic pollutants (POP) and breast cancer incidence in humans. This may be attributable to difficulties in estimating blood/tissue POP concentration at critical time periods of carcinogenesis.In this work we aimed to develop a tool to estimate lifetime POP blood/tissue exposure and levels during any hypothesized time window of susceptibility in breast cancer development.We developed a physiologically based pharmacokinetic (PBPK) model that can account for any given physiologic lifetime history. Using data on pregnancies, height, weight, and age, the model estimates the values of physiologic parameters (e.g., organ volume, composition, and blood flow) throughout a woman's entire life. We assessed the lifetime toxicokinetic profile (LTP) for various exposure scenarios and physiologic factors (i.e., breast-feeding, growth, pregnancy, lactation, and weight changes).Simulations for three POPs [hexachlorobenzene, polychlorinated biphenyl (PCB)-153, PCB-180] using different lifetime physiologic profiles showed that the same blood concentration at 55 years of age can be reached despite totally different LTP. Aside from exposure levels, lactation periods and weight profile history were shown to be the factors that had the greatest impact on the LTP.This new lifetime PBPK model, which showed the limitations of using a single sample value obtained around the time of diagnosis for lifetime exposure assessment, will enable researchers conducting environmental epidemiology studies to reduce uncertainty linked to past POP exposure estimation and to consider exposure during time windows that are hypothesized to be mechanistically critical in carcinogenesis.
Modern Treatment of Neurosyphilis
Authors: F. G. Lescher, H. R. M. Richards
Journal: BMJ (1947)

During the last eight years over 50 patients suffering from various types of neurosyphilis, chiefly in the earlier stages, have been treated in this clinic by three different methods.Twenty-five who had not responded satisfactorily to penta- valent arsenic and bismuth were treated by infection with tertian malaria, followed by chemotherapy (Lescher and Richards, 1944).Ten more were given penicillin alone; and a further 19 were treated by malaria combined with penicillin.Forty-seven have been followed up both clinic- ally and serologically, examinations of the spinal fluids having been made at definite intervals.It is our intention here to try to compare the results of these three different methods of treatment.Treatment of Neurosyphilis with Malaria and Chemotherapy Until recently it was considered that the most satisfactory method of treatment of neurosyphilis was with malaria, followed by tryparsamide and bismuth.The latest review is by Nicol (1946), who treated and followed up 217 patients suffering from taboparesis or dementia paralytica.Over 500% improved clinically, and in 70% the spinal fluids became negative.Of the 25 patients in our series who were treated by this method, 20 have been followed up for from five to eight years (Tables I andII).TABLE I.-Clinical Results after Treatment with Malaria and Chemotherapy Type No.Much Improved Improved IStationary Worse Meningovascular 'K.
Complement Protein C1q Inhibits Antibody-Dependent Enhancement of Flavivirus Infection in an IgG Subclass-Specific Manner
Authors: Erin Mehlhop, Camilo Ansarah-Sobrinho, Syd Johnson, Michael Engle, Daved H. Fremont, Theodore C. Pierson, Michael S. Diamond
Journal: Cell Host & Microbe (2007)
Threats to the Confidentiality of Medical Records—No Place to Hide
Authors: Paul S. Appelbaum
Journal: JAMA (2000)

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Research shows that South Africa deserves its poor reputation for tackling AIDS
Authors: R. Dobson
Journal: BMJ (2008)

South Africa’s reputation for poor leadership in the fight against AIDS is deserved, say authors of research ( Journal of Public Health 2008 Sep 12, doi:10.1093/pubmed/fdn075).⇓



HAART coverage (December 2006) and per capita income (2005)



The researchers, who compared access to AIDS drugs with need in more than 80 nations, found that South Africa performed significantly below expectations.

Brazil and Namibia were among several countries that performed better than expected.

The report says that despite an unprecedented mobilisation of resources worldwide since 2003, the …
THE RELATION OF SERUM ESTERASE TO LIVER DESTRUCTION
Authors: James W. Jobling, A. A. Eggstein, William Petersen
Journal: The Journal of Experimental Medicine (1915)

1. Liver tissue showing fatty degeneration obtained from animals poisoned with phosphorus or chloroform contains a decreased amount of esterase. 2. The serum of animals poisoned with phosphorus or chloroform has a high esterase activity. 3. The increased amount of esterase in the serum is not derived from the disintegrating liver cells as the esterase in the blood of the hepatic vein is less than that found elsewhere.