tbuckley/cabot-search huggingface dataset:
Six-Horse Rapids
Authors: Craig L. Bowron
Journal: Annals of Internal Medicine (2012)

Ad Libitum19 June 2012Six-Horse RapidsCraig L. Bowron, MDCraig L. Bowron, MDFrom Minneapolis, MN 55407.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-156-12-201206190-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Little children, some of them yours, ran pell-mell through the emptied chapel,oblivious to you and your urn,Distant from the adults out grieving in the narthex,nibbling on funeral food,staring at looping videos of you as you were, or out the windows,where snowflakes the size of nickels plunged into a March-brown cattail marsh.Your father and brothers shared stories of fishing expeditions north ... Author, Article, and Disclosure InformationAffiliations: From Minneapolis, MN 55407.Current Author Address: Craig L. Bowron, MD; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 June 2012Volume 156, Issue 12Page: 901KeywordsAdenocarcinomaBeerChildrenFoodLymph nodesMarshesNauseaSurgeryUlcers ePublished: 19 June 2012 Issue Published: 19 June 2012 Copyright & PermissionsCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
923. Muscle Stem Cells Genetically Modified to Express a VEGF Antagonist Display an Impaired Ability for Cardiac Repair
Authors: Thomas R. Payne, Hideki Oshima, Masaho Okada, Nobuo Momoi, Kimimasa Tobita, Bradley B. Keller, Hairong Peng, Johnny Huard
Journal: Molecular Therapy (2005)

Background: The exact mechanism by which cardiac cell transplantation exerts therapeutic improvements in cardiac function is unclear. One possible mechanism is that the transplanted cells act by promoting neoangiogenesis within the infarct through their release of angiogenic factors. Our previous research has demonstrated that skeletal muscle-derived stem cells (MDSCs) expressed vascular endothelial growth factor (VEGF), a potent angiogenic factor, after transplantation in infarcted hearts. These results led us to hypothesize that VEGF expression by the transplanted MDSCs mediates functional improvements. To test this hypothesis, we performed a set of experiments in which we genetically modified MDSCs to overexpress VEGF (gain-of-function) or overexpress soluble FLT-1, which is a soluble VEGF receptor and antagonist of VEGF (loss-of-function).
TWO YEARS' STUDY OF LOBAR PNEUMONIA IN MASSACHUSETTS
Authors: RODERICK HEFFRON
Journal: JAMA (1933)

Lobar pneumonia as a cause of death outranks all other infections, except tuberculosis. Standing in seventh or eighth place among the principal causes of death, it ranks second if one considers only persons in early adult life. In the United States Registration Area for the ten years 1920-1929 there were over one million deaths from all forms of pneumonia, 52 per cent of which were due to lobar pneumonia. Few if any diseases exact such a toll at the economic prime of life. It is therefore extremely fitting that in any consideration of public health some attention should be given to this disease. Yet almost without exception it has been completely neglected save for a passing remark of regret as to the futility of its control.  Quarantine seems to offer little hope of success, owing to the relative infrequency of secondary cases. A thoughtful health officer would hesitate to recommend
Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury
Authors: Masahiko Abematsu, Keita Tsujimura, Mariko Yamano, Michiko Saito, Kenji Kohno, Jun Kohyama, Masakazu Namihira, Setsuro Komiya, Kinichi Nakashima
Journal: Journal of Clinical Investigation (2010)

The body's capacity to restore damaged neural networks in the injured CNS is severely limited. Although various treatment regimens can partially alleviate spinal cord injury (SCI), the mechanisms responsible for symptomatic improvement remain elusive. Here, using a mouse model of SCI, we have shown that transplantation of neural stem cells (NSCs) together with administration of valproic acid (VPA), a known antiepileptic and histone deacetylase inhibitor, dramatically enhanced the restoration of hind limb function. VPA treatment promoted the differentiation of transplanted NSCs into neurons rather than glial cells. Transsynaptic anterograde corticospinal tract tracing revealed that transplant-derived neurons reconstructed broken neuronal circuits, and electron microscopic analysis revealed that the transplant-derived neurons both received and sent synaptic connections to endogenous neurons. Ablation of the transplanted cells abolished the recovery of hind limb motor function, confirming that NSC transplantation directly contributed to restored motor function. These findings raise the possibility that epigenetic status in transplanted NSCs can be manipulated to provide effective treatment for SCI.
Chess and the Computer
Authors: Charles L. Witte
Journal: JAMA (1979)

<h3>To the Editor.—</h3> Although I do not wish to belaborThe Journalwith a continuing chess dialogue, the inaccuracy of Dr Andrew Diosy's letter (240:1241, 1978) needs to be corrected. Chess master David Levy did not lose but rather beat the Northwestern University chess computer in their recent match (3 1/2 - 1 1/2) and won the wager of £1,250 (<i>Arizona Daily Star</i>, Sept 7, 1978, p 2), now worth only $2,500. While properly imbued with the intangibles of medical practice, Dr Diosy has also been misled when he implies that winning at chess is purely a sterile, programmable achievement. After mastery of the basic ground rules (ie, the chess algorithm), the ultimate ingredients of chessical skill—imagination, originality, ingenuity, open-mindedness, and a creative grasp of strategy and tactics— are not easily computerized. In fact, these strong personality traits are inimical to medical algorithm enthusiasts, who delight in a certain rigidity of
Pivotal Role of Rho-Associated Kinase 2 in Generating the Intrinsic Circadian Rhythm of Vascular Contractility
Authors: Toshiro Saito, Mayumi Hirano, Tomomi Ide, Toshihiro Ichiki, Noriyuki Koibuchi, Kenji Sunagawa, Katsuya Hirano
Journal: Circulation (2012)

The circadian variation in the incidence of cardiovascular events may be attributable to the circadian changes in vascular contractility. The circadian rhythm of vascular contractility is determined by the interplay between the central and peripheral clocks. However, the molecular mechanism of the vascular intrinsic clock that generates the circadian rhythm of vascular contractility still remains largely unknown.The agonist-induced phosphorylation of myosin light chain in cultured smooth muscle cells synchronized by dexamethasone pulse treatment exhibited an apparent circadian oscillation, with a 25.4-hour cycle length. The pharmacological inhibition and knockdown of Rho-associated kinase 2 (ROCK2) abolished the circadian rhythm of myosin light chain phosphorylation. The expression and activity of ROCK2 exhibited a circadian rhythm in phase with that of myosin light chain phosphorylation. A clock gene, RORα, activated the promoter of the ROCK2 gene, whereas its knockdown abolished the rhythmic expression of ROCK2. In the mouse aorta, ROCK2 expression exhibited the circadian oscillation, with a peak at Zeitgeber time 0/24 and a nadir at Zeitgeber time 12. The myofilament Ca(2+) sensitization induced by GTPγS and U46619, a thromboxane A2 analog, at Zeitgeber time 0/24 was greater than that seen at Zeitgeber time 12. The circadian rhythm of ROCK2 expression and myofilament Ca(2+) sensitivity was abolished in staggerer mutant mice, which lack a functional RORα.ROCK2 plays a pivotal role in generating the intrinsic circadian rhythm of vascular contractility by receiving a cue from RORα. The ROCK2-mediated intrinsic rhythm of vascular contractility may underlie the diurnal variation of the incidence of cardiovascular diseases.
IMPAIRMENT OF ANTIBODY RESPONSE IN PYRIDOXINE-DEFICIENT RATS
Authors: Herbert C. Stoerk, Herman N. Eisen, Hedda M. John
Journal: The Journal of Experimental Medicine (1947)

Striking impairment of the antibody response to sheep erythrocytes was found in pyridoxine-deficient rats. Deficiencies in the three other B factors required by the rat, and low protein feeding, having effects on body weight comparable to pyridoxine deficiency, failed to influence the antibody response studied. Confirming previous observations, a striking loss of thymic and lymphoid tissue occurred in the pyridoxine-deficient animals. A marked deficit in thymus weight also resulted from the feeding of a diet low in thiamin. Histologically, however, lymphoid atrophy was less pronounced in thiamin-deficient rats than in those deprived of pyridoxine.
Retinal Vascular Reactivity in Patients with Diabetes Mellitus and with Atherosclerosis
Authors: J. B. HICKAM, H. O. SIEKER
Journal: Circulation (1960)

By means of fundus photography, a comparative study has been made of the constrictor response of retinal vessels to the inhalation of oxygen in 47 control subjects, 50 diabetic patients, and 15 persons with atherosclerosis unassociated with hypertension or diabetes. The diabetic group showed decreased reactivity of both arteries and veins, as indicated by a decreased constrictor response to oxygen. Retinal arterial reactivity was significantly reduced in diabetic subjects, even in the absence of retinopathy or hypertension. With the appearance of retinopathy, arterial reactivity was still further reduced. The patients with uncomplicated atherosclerosis did not show significant changes in retinal vascular reactivity.
Discrepancies in the Reported Frequency of Cocaine-Related Deaths, United States, 1983 Through 1988
Authors: Daniel A. Pollock
Journal: JAMA (1991)

<h3>Objective.</h3> —To assess the validity of cocaine-related mortality data available from the principal federal sources of information about the frequency of drug abuse deaths in the United States: the national vital statistics system and the Drug Abuse Warning Network (DAWN). <h3>Design, Setting, and Participants.</h3> —We compared the number of cocaine-related deaths reported to national vital statistics and DAWN from 25 metropolitan areas during the years 1983 through 1988. We also compared cocaine-related mortality data reported to national vital statistics with data from all published forensic case series of cocaine-related deaths that occurred during the mid-1980s. <h3>Results.</h3> —During the 6-year study period, 75% more cocaine-related deaths were reported to DAWN (6057) than to national vital statistics (3466) from the 25 metropolitan areas that we studied. For individual metropolitan areas, the discrepancy between DAWN and vital statistics counts of cocaine-related deaths was as large as a sixfold difference. In six of the seven forensic case series identified in our literature search, the number of cocaine-related deaths exceeded the number of these deaths reported to vital statistics. The largest discrepancy was for cocaine-related deaths in New York, NY, during a 10-month period in 1986 for which 151 deaths were reported in a case series and seven deaths were reported to vital statistics. <h3>Conclusion.</h3> —Improvements in existing public health surveillance systems are needed for (1) full and accurate measurements of the lethal impact of drug abuse epidemics and (2) valid and comprehensive assessments of the effectiveness of national programs designed to prevent drug-related morbidity and mortality. (<i>JAMA</i>. 1991;266:2233-2237)
A Phase Ib Dose-Escalation Study of the Oral Pan-PI3K Inhibitor Buparlisib (BKM120) in Combination with the Oral MEK1/2 Inhibitor Trametinib (GSK1120212) in Patients with Selected Advanced Solid Tumors
Authors: Philippe L. Bedard, Josep Tabernero, Filip Janku, Zev A. Wainberg, Luis Paz-Ares, Johan Vansteenkiste, Eric Van Cutsem, José Pérez-García, Anastasios Stathis, Carolyn D. Britten, Ngocdiep Le, Kirsten Carter, David Demanse, Denes Csonka, Malte Peters, Angela Zubel, Heidi Nauwelaerts, Cristiana Sessa
Journal: Clinical Cancer Research (2014)

MAPK and PI3K/AKT/mTOR pathways play important roles in many tumors. In this study, safety, antitumor activity, and pharmacokinetics of buparlisib (pan class PI3K inhibitor) and trametinib (MEK inhibitor) were evaluated.This open-label, dose-finding, phase Ib study comprised dose escalation, followed by expansion part in patients with RAS- or BRAF-mutant non-small cell lung, ovarian, or pancreatic cancer.Of note, 113 patients were enrolled, 66 and 47 in dose-escalation and -expansion parts, respectively. MTD was established as buparlisib 70 mg + trametinib 1.5 mg daily [5/15, 33% patients with dose-limiting toxicities (DLT)] and recommended phase II dose (RP2D) buparlisib 60 mg + trametinib 1.5 mg daily (1/10, 10% patients with DLTs). DLTs included stomatitis (8/103, 8%), diarrhea, dysphagia, and creatine kinase (CK) increase (2/103, 2% each). Treatment-related grade 3/4 adverse events (AEs) occurred in 73 patients (65%); mainly CK increase, stomatitis, AST/ALT (aspartate aminotransferase/alanine aminotransferase) increase, and rash. For all (21) patients with ovarian cancer, overall response rate was 29% [1 complete response, 5 partial responses (PR)], disease control rate 76%, and median progression-free survival was 7 months. Minimal activity was observed in patients with non-small cell lung cancer (1/17 PR) and pancreatic cancer (best overall response was SD). Relative to historical data, buparlisib exposure increased and trametinib exposure slightly increased with the combination.At RP2D, buparlisib 60 mg + trametinib 1.5 mg daily shows promising antitumor activity for patients with KRAS-mutant ovarian cancer. Long-term tolerability of the combination at RP2D is challenging, due to frequent dose interruptions and reductions for toxicity.
Serologic Evidence of Previous Campylobacter jejuni Infection in Patients with the Guillain-Barre Syndrome
Authors: Ban Mishu
Journal: Annals of Internal Medicine (1993)

Objective: To determine if patients with the Guillain-Barre syndrome are likely to have had Campylobacter jejuni infection before onset of neurologic symptoms. Design: A case–control study. Setting: Several university medical centers. Patients: Case patients met clinical criteria for the Guillain-Barre syndrome between 1983 and 1990 and had a serum sample collected and frozen within 3 weeks after onset of neurologic symptoms (n = 118). Disease controls were patients with other neurologic illnesses (n = 56); healthy controls were hospital employees or healthy family members of patients (n = 47). Measurements: Serum IgA, IgG, and IgM antibodies to C. jejuni were determined by enzyme-linked immunosorbent assays. Assays were done in a blinded manner. Results: Optical density ratios 2 in two or more immunoglobulin classes were seen in 43 (36%) of patients with the Guillain-Barre syndrome and in 10 (10%) of controls (odds ratio, 5.3; 95% CI, 2.4 to 12.5; P < 0.001). Increasing the optical density ratio or the number of immunoglobulin classes necessary to yield a positive result increased the strength of the association. The number of patients with the Guillain-Barre syndrome who had positive serologic responses was greatest from September to November (P = 0.02). Male patients were three times more likely to have serologic evidence of C. jejuni infection (P = 0.009); the proportion of patients with the syndrome who had a positive serologic response increased with age. Conclusions: Patients with the Guillain-Barre syndrome are more likely than controls to have serologic evidence of C. jejuni infection in the weeks before onset of neurologic symptoms. Campylobacter jejuni may play a role in the initiation of the Guillain-Barre syndrome in many patients.
Validating cultural transmission in cetaceans
Authors: Rachel L. Day, Jeremy R. Kendal, Kevin N. Laland
Journal: Behavioral and Brain Sciences (2001)

The evidence of high cognitive abilities in cetaceans does not stand up to close scrutiny under the standards established by laboratory researchers. This is likely to lead to a sterile debate between laboratory and field researchers unless fresh ways of taking the debate forward are found. A few suggestions as to how to do this are proposed.
Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome
Authors: Susan Lapthorne, Prue M. Pereira-Fantini, Fiona Fouhy, Guineva Wilson, Sarah L. Thomas, Nicole L. Dellios, Michelle Scurr, Orla O’Sullivan, R. Paul Ross, Catherine Stanton, Gerald F. Fitzgerald, Paul D. Cotter, Julie E. Bines
Journal: Gut Microbes (2013)

Following small bowel resection (SBR), the luminal environment is altered, which contributes to clinical manifestations of short bowel syndrome (SBS) including malabsorption, mucosal inflammation and bacterial overgrowth. However, the impact of SBR on the colon has not been well-defined. The aims of this study were to characterize the colonic microbiota following SBR and to assess the impact of SBR on mucosal inflammation in the colon.Analysis of the colonic microbiota demonstrated that there was a significant level of dysbiosis both two and six weeks post-SBR, particularly in the phylum Firmicutes, coupled with a decrease in overall bacterial diversity in the colon. This decrease in diversity was associated with an increase in colonic inflammation six weeks post-surgery.Female (4-week old) piglets (5-6/group) received a 75% SBR, a transection (sham) or no surgery. Compositional analysis of the colonic microbiota was performed by high-throughput sequencing, two- and six-weeks post-surgery. The gene expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α in the colonic mucosa was assessed by qRT-PCR and the number of macrophages and percentage inducible nitric oxide synthase (iNOS) staining in the colonic epithelium were quantified by immunohistochemistry.SBR significantly decreased the diversity of the colonic microbiota and this was associated with an increase in colonic mucosal inflammation. This study supports the hypothesis that SBR has a significant impact on the colon and that this may play an important role in defining clinical outcome.
Better standards for better reporting of RCTs
Authors: P. M M Bossuyt
Journal: BMJ (2001)

In the first months of their scientific training students are taught the importance of transparent descriptions of methods and results in scientific communication. Scientists exchange not only beliefs and opinions but also, and primarily, observations and the methods used to obtain them—exposing them to critical scrutiny and the possibility of replication.

These days, not just scientists turn to the medical literature. Clinical practitioners and other decision makers search Medline in the hope of finding evidence in valid studies that apply to their problems. Most decision makers do not even think about or have the means for replicating studies. Yet in this era of evidence based medicine all are aware of the necessity of critical appraisal: to examine the results, not just the opinions; to judge the potential for bias in the design, conduct, analysis, and interpretation of studies; and to evaluate the generalisability (or otherwise) of the findings.

Randomised clinical trials are rightfully regarded as the best tools for gathering evidence on the effectiveness of health care interventions. Unfortunately, the maturity of randomised trials, now …
Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases
Authors: Mingjiang Xu, Edward Bruno, Joseph Chao, Stephen Huang, Guido Finazzi, Steven M. Fruchtman, Uday Popat, Josef T. Prchal, Giovanni Barosi, Ronald Hoffman
Journal: Blood (2005)
A gastric submucosal mass: Emad EI-Omar, Editor
Authors: S. D. Chowdhury, A. Joseph, A. Pulimood, A. Eapen, V. Abraham, J. John, A. Chacko
Journal: Gut (2010)

A 42-year-old male was referred with epigastric pain of insidious onset, progressive over a duration of 3 months. Pain was non-radiating, continuous, with no specific aggravating or relieving factors. There was no loss of appetite or loss of weight. …
Photosensitive Cheilitis
Authors: ROBERT R. RICH
Journal: Annals of Internal Medicine (1971)

A case of photosensitive cheilitis, a disease predominantly found in Africans, is described in a negro American. It is characterized by painful, chronic ulceration of the lower lip, induced by solar radiation. Studies to elucidate the pathogenesis of the disease showed that the mechanisms of repair of ultraviolet-damaged DNA were normal, thus excluding a defect analogous to that in xeroderma pigmentosum. However, the basal turnover of thymidine in lymphocytes not irradiated with ultraviolet light was excessive. Furthermore, ultrastructural studies of damaged lip tissues showed nuclear bodies and microtubular cytoplasmic aggregates in endothelial cells. Because similar findings have been seen in virus-infected tissues, activation of latent virus infection is suggested as an etiologic mechanism in photosensitive cheilitis.
Bringing nurses and doctors closer together
Authors: N. Casey, R. Smith
Journal: BMJ (1997)

Background/Aim: Using drains after breast surgery is a preventive, but invasive measure to reduce seroma formation. A polyurethane-based tissue adhesive (TissuGlu®) might facilitate drainage-free wound healing after mastectomy in a non-invasive manner. Patients and Methods: Retrospectively, data from 84 patients (42 receiving TissuGlu®, 42 receiving a drainage) who underwent mastectomy, were collected (90 days postoperative follow-up). Study endpoints were defined as the number of fluid-related postoperative clinical interventions, cumulative volume of postoperative wound fluid, duration of hospitalization and postoperative complications. Results: In the entirety of postoperative interventions, no significant difference could be demonstrated (p=0.298). The drainage arm showed significantly less seroma aspirations (p=0.024) and complications (p=0.012). A significantly reduced length of hospitalization (p&lt;0.001) and less cumulative wound secretion volume (p&lt;0.001) appeared in the TissuGlu® group. Conclusion: The polyurethane-based tissue adhesive is a less invasive alternative to drain use in mastectomy.