tbuckley/cabot-search huggingface dataset:
Suppression of plasma renin activity by indomethacin in man.
Authors: J C Frölich, J W Hollifield, J C Dormois, B L Frölich, H Seyberth, A M Michelakis, J A Oates
Journal: Circulation Research (1976)

The effect of indomethacin or placebo on aldosterone, plasma renin activity (PRA), sodium excretion, and urinary prostaglandin (PG) levels was investigated in five hypertensive subjects in 100 mEq sodium balance who had experienced malignant hypertension with a disturbance of their renin-aldosterone relationship in the past. Indomethacin significantly lowered aldosterone levels by 43%, PRA by 58%, 24-hour sodium excretion by 49%, and urinary PG excretion, an indicator of renal PG synthesis, by 67%. Angiotensin infusion increased aldosterone to the same level before and after treatment with indomethacin. Similarly, in normal subjects in 150 mEq sodium balance, indomethacin lowered PRA by 47%; sodium excretion fell by 33%, and urinary prostaglandin E (PGE) excretion, by 55%. The acute elevation in PRA 10 minutes after intravenous furosemide was completely abolished by indomethacin. Five subjects with essential hypertension were classified as normal renin hypertensives according to their response to orally administered furosemide. Indomethacin pretreatment resulted in 60% reduction of PRA following furosemide, and three of these subjects now fell into the low renin category. Studies in vitro demonstrated that indomethacin has no effect on the renin-renin substrate interaction. Thus, indomethacin lowers PRA concomitantly with a reduction in renal PG synthetase activity. Whether indomethacin inhibits renin release by an intrarenal, PG-related mechanism or secondarily via sodium retention is discussed.
Adherence to Stage-Specific Treatment Guidelines for Patients With Colon Cancer
Authors: Ryaz Chagpar, Yan Xing, Yi-Ju Chiang, Barry W. Feig, George J. Chang, Y. Nancy You, Janice N. Cormier
Journal: Journal of Clinical Oncology (2012)

Purpose Adherence to evidence-based treatment guidelines has been proposed as a measure of cancer care quality. We sought to determine rates of and factors associated with adherence to the National Comprehensive Cancer Network (NCCN) treatment guidelines for colon cancer. Patients and Methods Patients within the National Cancer Data Base treated for colon adenocarcinoma (2003 to 2007) were identified. Adherence to stage-specific NCCN guidelines was determined based on disease stage. Hierarchical regression analyses were performed to identify factors predictive of adherence, overtreatment, and undertreatment. Results A total of 173,243 patients were included in the final cohort, 123,953 (71%) of whom were treated according to NCCN guidelines. Patients with stage I disease were more likely to receive guideline-based treatment (96%) than patients with stage II (low risk, 66%; high risk, 36%), III (71%), or IV (73%) disease (P &lt; .001). Adherence to consensus-based guidelines increased over time. Factors associated with adherence across all stages included age, Charlson-Deyo comorbidity index score, later year of diagnosis, and insurance status. Among patients with high-risk stage II or stage III disease, older patients with pre-existing comorbidities and patients with lower socioeconomic status were less likely to be offered adjuvant chemotherapy. Among patients with stage I and II disease, young, healthy patients were more likely to be recommended chemotherapy, in discordance with NCCN guidelines. Conclusion Significant variation exists in the treatment of colon cancer, particularly in treatment of high-risk stage II and stage III disease. The impact of nonadherence to guidelines on patient outcomes needs to be further elucidated.
Doping is a threat to sporting excellence
Authors: John William Devine
Journal: British Journal of Sports Medicine (2010)

Savulescu et al have argued that the risk to athletes' welfare provides the only legitimate ground for restricting the use of performance enhancing drugs in sport. In this paper, it is argued that the idea of `sport', properly understood, provides further reason to impose such restrictions. A `balance of excellences' argument is proposed whereby doping is considered objectionable on account of its disrupting the relation between the excellences around which sporting competition is organised. We have reason to restrict the use of performance enhancing drugs in sport not only because of the threat they pose to athletes' health but also because of the threat they pose to athletes' displaying the relevant types of sporting excellence.
Re: Cough-Induced Cardiac Compression
Authors: J. Michael Griley
Journal: JAMA (1977)

<h3>To the Editor.—</h3> In a recent article entitled "Cough-Induced Cardiac Compression" (236:1246, 1976), we describe a 20-year-old patient in whom ventricular asystole developed during interruption of cardiac pacing; this incident was included to establish that cardiac arrest leads to unconsciousness in less than the observed time of sustained consciousness in the patients with cardiac arrest who underwent "cough-induced CPR." In order to clarify the circumstances under which the observations on the patient with the pacemaker were made, it should be noted that the asystole occurred during the changeover from a temporary to a permanent pulse generator (pacemaker), and when pacemaker dependency was observed, all due haste was exercised in completing the electrical connection to the permanent generator. The ECG record documented the duration of asystole, as well as the time of onset of the seizure episode. It should be stressed that the prolonged deprivation of pacing was not intentional, but resulted
Chronic intrahepatic cholestasis in sickle cell disease requiring exchange transfusion.
Authors: A O'Callaghan, S G O'Brien, M Ninkovic, G P Butcher, C S Foster, J R Walters, I A Roberts
Journal: Gut (1995)

A 15 year old boy with sickle cell disease developed intrahepatic cholestasis. A course of exchange transfusion successfully corrected the extreme hyperbilirubinaemia over one year. Upon stopping the exchange transfusion programme the hyperbilirubinaemia relapsed but transfusion was effective when reinstituted.
Expression of MAP4K4 Is Associated with Worse Prognosis in Patients with Stage II Pancreatic Ductal Adenocarcinoma
Authors: John J. Liang, Hua Wang, Asif Rashid, Tse-Hua Tan, Rosa F. Hwang, Stanley R. Hamilton, James L. Abbruzzese, Douglas B. Evans, Huamin Wang
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Mitogen-activated protein 4 kinase 4 (MAP4K4) is a serine/threonine kinase and belongs to the mammalian STE20/MAP4K family. Recent studies have shown that MAP4K4 is overexpressed in many types of human cancer and cancer cell lines. MAP4K4 plays an important role in transformation, invasiveness, adhesion, and cell migration. However, the expression of MAP4K4 and its significance in pancreatic ductal adenocarcinoma (PDA) has not been studied. Experimental Design: We examined the expression of MAP4K4 by immunohistochemistry using tissue microarrays consisting of 66 stage II PDA and their paired benign pancreatic tissue. The staining results were categorized as MAP4K4-H or MAP4K4-L. The results were correlated with clinicopathologic features and patient survival. Results: MAP4K4 was overexpressed (MAP4K4-H) in 30 of 66 (46%) PDAs and was higher than the paired benign pancreatic tissue samples (19%; P = 0.002). The median overall and recurrence-free survival for patients with MAP4K4-H PDAs were 19.5 and 9.3 months, respectively, compared with 65.2 and 28.8 months for patients with MAP4K4-L tumor (P = 0.02 and 0.0005, log-rank test). MAP4K4 expression was associated with poor overall and recurrence-free survival in univariate analysis (P = 0.02 and 0.001). In multivariate analysis, MAP4K4 expression significantly correlated with overall and recurrence-free survival (P = 0.025 and 0.004) independent of age, tumor size, differentiation, and stage. MAP4K4 expression was also associated with higher frequency of recurrence/metastasis, larger tumor size, and increased number of positive lymph nodes (P &amp;lt; 0.05). Conclusion: MAP4K4 was overexpressed in about half of PDAs. Overexpression of MAP4K4 was associated with worse prognosis and is a prognostic marker for stage II PDAs.
BTS guidelines for the management of pleural infection in children
Authors: I M Balfour-Lynn
Journal: Thorax (2005)

<h3>Background</h3> The purpose of this study was to evaluate the incidence, timing and risk factors of corneal neovascularisation (NV) after deep anterior lamellar keratoplasty (DALK) for corneal ectasia. <h3>Methods</h3> This study included 616 eyes who underwent DALK between 2012 and 2020 in two tertiary referral centres. In one centre topical corticosteroids were discontinued after complete suture removal 1 year after surgery, whereas in the other they were discontinued 3–4 months after surgery. The presence and severity of corneal NV was ascertained based on slit lamp photographs. Potential risk factors for corneal NV were evaluated using the Cox proportional hazards model. <h3>Results</h3> The cumulative incidence of corneal NV was 8.7% at 1 year after surgery and 13.2% at 5 years. Mean time interval from surgery to development of corneal NV was 12.8±16.2 months, with 68.9% of cases occurring before complete suture removal. Early discontinuation of topical steroids, older age and ocular allergy were associated with an increased risk of developing corneal NV (respectively, HR=2.625, HR=1.019, HR=3.726, all p&lt;0.05). <h3>Conclusions</h3> The risk of corneal NV is higher in the first year following DALK. Early discontinuation of topical steroids, ocular allergy and older age are significant predictors of corneal NV.
A FATAL CASE OF ACUTE MERCURIAL POISONING
Authors: E. S. Sugden
Journal: BMJ (1905)

CAASES of acute mercurial poisoning are so rare and the litera- ture so sparse that I think it desirable to place on record this well-marked case.A young lady, 23 years of age, on October ist swallowed, mixed in a tablespoonful of milk, a " headache powder," pro- cured from a local chemist's shop.Immediately after taking the powder she was seized with a severe burning pain in the throat and with vomiting; she vomited again in a few
Is Telomeropathy the Explanation for Combined Pulmonary Fibrosis and Emphysema Syndrome?: Report of a Family with TERT Mutation
Authors: Hilario Nunes, Isabelle Monnet, Caroline Kannengiesser, Yurdagul Uzunhan, Dominique Valeyre, Marianne Kambouchner, Jean-Marc Naccache
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Sinoventricular transmission in 10 mM K+ by canine atrioventricular nodal inputs. Superior atrionodal bundle and proximal atrioventricular bundle.
Authors: D K Racker
Journal: Circulation (1991)

BACKGROUND This study was done to determine the electrical properties of the superior atrionodal bundle (SAB) and the proximal atrioventricular bundle (PAVB). METHODS AND RESULTS Extracellular potentials associated with electrical activity in the SAB and PAVB were identified in electrograms using adult canine atrial preparations in which the AV node (AVN) and distal AV (His) bundle (DAVB) had been exposed. Intracellular potentials and/or electrograms of the sinoatrial node (SAN), SAB, PAVB, AVN, DAVB, and atrial contractions from a pectinate muscle bundle in the high right atrial wall were recorded. The electrograms contained deflections representing discharge of the specific tissues and atrial potentials from the adjacent or overlying atrial contractile myocardium. In superfusates containing 2.7 mM K+, sequential discharge of the tissues resulted in brief SAN-SAB, PAVB-DAVB, and AVN-DAVB intervals and a major delay after discharge of the SAB. The delay was attributed to activation of the PAVB, as reflected in extracellular PAVB potentials of long duration. Atrial potentials and the onset of the contractile event followed discharge of the SAN and SAB but preceded activation of the PAVB, AVN, and DAVB. After transection of the PAVB-AVN connections, the AVN exhibited automaticity, but the SAB, PAVB, atrial potentials in all of the electrograms, and atrial contractions persisted at the sinus rate. During exposure to 10 mM K+, atrial potentials in all of the electrograms and atrial contractions ceased, indicating electrical quiescence of the contractile myocardium; however, the unique pattern of discharge of the SAB, PAVB, AVN, and DAVB persisted at the SA nodal rate. CONCLUSIONS Thus, the SAB and PAVB can be classified as specialized conducting tissues and are intrinsic components of the internodal conductile pathway.
Heart Failure Is a Risk Factor for Orthopedic Fracture
Authors: Sean van Diepen, Sumit R. Majumdar, Jeffrey A. Bakal, Finlay A. McAlister, Justin A. Ezekowitz
Journal: Circulation (2008)

Heart failure (HF) is associated with factors that may contribute to accelerated bone loss and subsequent fractures. Whether it leads to an increased fracture risk is unknown.A population-based cohort of consecutive patients >/=65 years of age with cardiovascular disease presenting to all emergency rooms between 1998 and 2001 in Alberta, Canada (n=16294 patients), was used. The 2041 patients with a new diagnosis of HF were compared with a control group of 14 253 patients with non-HF cardiovascular diagnoses. The primary outcome was any orthopedic fracture requiring hospital admission in the year after the emergency room visit. Patients with HF had a median age of 78 years (interquartile range, 72 to 84 years), and 51.9% were female; control subjects had a median age of 73 years (interquartile range, 68 to 79 years), and 53.2% were female. In the first year after the emergency room visit, 4.6% of the HF cohort (n=93) and 1.0% of patients without HF (n=147) sustained an orthopedic fracture (P<0.001). Hip fractures occurred in 26 HF patients (1.3%) and 18 patients (0.1%) without HF (P<0.001). After multivariable adjustment, HF was independently associated with a greater risk of any orthopedic fracture (adjusted odds ratio, 4.0; 95% CI, 2.9 to 5.3) or hip fracture (adjusted odds ratio, 6.3; 95% CI, 3.4 to 11.8).HF is associated with an increased risk of subsequent orthopedic fracture, particularly hip fracture. This suggests that screening for and treatment of osteoporosis to reduce fracture risk need to be considered in those with HF.
Imatinib mesylate (STI571) therapy for Philadelphia chromosome–positive chronic myelogenous leukemia in blast phase
Authors: Hagop M. Kantarjian, Jorge Cortes, Susan O'Brien, Francis J. Giles, Maher Albitar, Mary Beth Rios, Jianqin Shan, Stefan Faderl, Guillermo Garcia-Manero, Deborah A. Thomas, Debra Resta, Moshe Talpaz
Journal: Blood (2002)
Wnt/β-Catenin Signaling Promotes Renal Interstitial Fibrosis
Authors: Weichun He, Chunsun Dai, Yingjian Li, Gang Zeng, Satdarshan P. Monga, Youhua Liu
Journal: Journal of the American Society of Nephrology (2009)

Wnts compose a family of signaling proteins that play an essential role in kidney development, but their expression in adult kidney is thought to be silenced. Here, we analyzed the expression and regulation of Wnts and their receptors and antagonists in normal and fibrotic kidneys after obstructive injury. In the normal mouse kidney, the vast majority of 19 different Wnts and 10 frizzled receptor genes was expressed at various levels. After unilateral ureteral obstruction, all members of the Wnt family except Wnt5b, Wnt8b, and Wnt9b were upregulated in the fibrotic kidney with distinct dynamics. In addition, the expression of most Fzd receptors and Wnt antagonists was also induced. Obstructive injury led to a dramatic accumulation of beta-catenin in the cytoplasm and nuclei of renal tubular epithelial cells, indicating activation of the canonical pathway of Wnt signaling. Numerous Wnt/beta-catenin target genes (c-Myc, Twist, lymphoid enhancer-binding factor 1, and fibronectin) were induced, and their expression was closely correlated with renal beta-catenin abundance. Delivery of the Wnt antagonist Dickkopf-1 gene significantly reduced renal beta-catenin accumulation and inhibited the expression of Wnt/beta-catenin target genes. Furthermore, gene therapy with Dickkopf-1 inhibited myofibroblast activation; suppressed expression of fibroblast-specific protein 1, type I collagen, and fibronectin; and reduced total collagen content in the model of obstructive nephropathy. In summary, these results establish a role for Wnt/beta-catenin signaling in the pathogenesis of renal fibrosis and identify this pathway as a potential therapeutic target.
The dream of a vaccine against tuberculosis; new vaccines improving or replacing BCG?
Authors: C. Martín
Journal: European Respiratory Journal (2005)

In the last 10 yrs, work with experimental laboratory models has developed many new vaccine candidates against tuberculosis (TB). They include subunit vaccines, modified bacilli Calmette-Guérin (BCG) and attenuated Mycobacterium tuberculosis . Phase I clinical trials of new TB vaccine candidates have begun for the first time after 80 yrs of use of BCG. Many of these new trials involve recombinant BCG or improve BCG immunity by boosting with vaccines consisting of subunits or attenuated vaccinia virus expressing TB antigens. However, effective vaccination against TB presents diverse and complex challenges. For example, TB infection can become reactivated years later and infection does not guarantee resistance to a subsequent second infection. A truly effective TB vaccine may, therefore, have to elicit an immune response that is greater than that induced by natural infection. In addition, various different populations have to be protected including those vaccinated with BCG and those infected with M. tuberculosis or HIV. The goal is a new generation of vaccines effective against respiratory forms of tuberculosis. As a first step, good candidate vaccines able to boost bacille Calmette-Guérin and thereby improve protection could be a reality in the near future. Tuberculosis vaccine candidates, able to replace the currently used bacille Calmette-Guérin and/or make the eradication of tuberculosis feasible, can only be expected in the long-term, and safe live vaccines could be promising candidates.
Particulate allergens aggravate allergic asthma in mice
Authors: Abiramy Jeyabalan
Journal: Thorax (2011)

Ambient inhalable particulate matter acts as an efficient carrier of allergens allowing penetration deep into the distal airways. Epidemiological studies have shown an association between the increased incidence of asthma and levels of ambient particulate matter from air pollutants. Most experimental models investigating the pathogenesis of allergic asthma have used soluble allergens (sAgs) whereas knowledge …
Intraprostatic Chemotherapy: Distribution and Transport Mechanisms
Authors: M. Guillaume Wientjes, Jenny H. Zheng, Leijun Hu, Yuebo Gan, Jessie L-S. Au
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The present study evaluated the tissue distribution and targeting advantage of intraprostatic chemotherapy. Experimental Design: We studied the delivery and spatial distribution of a fluorescent drug, doxorubicin, in the prostate of beagle dogs, after intraprostatic or i.v. administration. Drug concentrations were measured using high-performance liquid chromatography and confocal fluorescence microscopy. Results: I.v. and intraprostatic injections yielded qualitatively and quantitatively different doxorubicin distribution in the prostate. A relatively homogeneous distribution was found after i.v. administration, whereas intraprostatic injection yielded a highly heterogeneous distribution with &amp;gt;10-fold higher concentrations localized in a cone-shaped glandular lobule bound by fibromuscular stroma, compared with other parts of the prostate. Compared with i.v. injection, intraprostatic injection yielded, on average, ∼100-fold higher tissue-to-plasma concentration ratio, ranging from 963-fold near the injection site to 19-fold in the contralateral half of the prostate. The drug distribution within the prostate further suggests an important role for acinar flow in intraprostatic drug transport. Conclusions: Intraprostatic administration represents a viable option to deliver high drug concentrations within the prostate. The results further suggest the fibromuscular stroma separating the prostatic lobules as a major barrier to drug transport and convective flow as an important drug transport mechanism in the prostate.
Retreatment with trastuzumab-based therapy after disease progression following lapatinib in HER2-positive metastatic breast cancer
Authors: S. Gori, F. Montemurro, S. Spazzapan, G. Metro, J. Foglietta, G. Bisagni, A. Ferzi, R.R. Silva, T. Gamucci, M. Clavarezza, L. Stocchi, A. Fabi, F. Cognetti, E. Torrisi, D. Crivellari
Journal: Annals of Oncology (2011)
Localized Fat Atrophy after Jelly-fish Sting
Authors: M. A. R. Gunn
Journal: BMJ (1949)

The feature of interest in this case is the relation of the long-standing psychological disturbance to the development of oesophageal cancer.Lawrence Abel (1929) states that two-thirds of his cases of carcinoma of the oesophagus were preceded by an incident of emotional stress, and Guigez (1925) has said that half of the cases in his series had a similar history.Abel suggests that the neoplasm arises at the site of pre-existing spasm of the muscle wall, and refers to his own observations and those of Guisez that mental stress is often a cause of oesophageal spasm.If the patient's symptoms before the development of car- cinoma had been due to oesophageal spasm, it is reasonable to suppose that during the twenty-years history some of the oesophageal dilatation and hypertrophy characteristically the result of spasm ought to have developed.This was not so, and one is forced to the conclusion that in this patient, at any rate, whatever aetiological relation there may have been between mental stress and oesophageal cancer, spasm played no part.
Telomeres, Telomerase, and Immortality
Authors: M. S. Rhyu
Journal: JNCI Journal of the National Cancer Institute (1995)

A current hypothesis gaining prominence proposes that activation of the enzyme telomerase is necessary for cells to become immortal, or capable of proliferating indefinitely. The theory suggests that almost all cancer cells must attain immortality for progression to malignant states and, hence, require activation of telomerase. This article reviews the function and formation of telomeres as background to evaluating the "telomere hypothesis." Experiments in support of and experiments that challenge the hypothesis are examined. Possible approaches to telomerase inhibition are discussed.
Gut adaptation and the glucagon-like peptides
Authors: D J Drucker
Journal: Gut (2002)

The glucagon-like peptides GLP-1 and GLP-2 are synthesised and then released from enteroendocrine cells in the small and large intestine. GLP-1 promotes efficient nutrient assimilation while GLP-2 regulates energy absorption via effects on nutrient intake, gastric acid secretion and gastric emptying, nutrient absorption, and mucosal permeability. Preliminary human studies indicate that GLP-2 may enhance energy absorption and reduce fluid loss in subjects with short bowel syndrome suggesting that GLP-2 functions as a key regulator of mucosal integrity, permeability, and nutrient absorption. Hence GLP-2 may be therapeutically useful in diseases characterised by injury or dysfunction of the gastrointestinal epithelium.
Decreased baroreflex sensitivity is linked to sympathovagal imbalance, body fat mass and altered cardiometabolic profile in pre-obesity and obesity
Authors: Jagadeeswaran Indumathy, Gopal Krushna Pal, Pravati Pal, Palakkad Hariharan Ananthanarayanan, Subash Chandra Parija, Jayaraman Balachander, Tarun Kumar Dutta
Journal: Metabolism (2015)