tbuckley/cabot-search huggingface dataset:
Is the hypotension of cirrhosis a GABA-mediated process?
Authors: Gerald Y. Minuk, Keith L. Maccannell
Journal: Hepatology (1988)

Systolic and diastolic blood pressures were recorded in 176 ambulant patients with chronic liver disease, including 36 patients with compensated cirrhosis (Group I), 119 patients with noncirrhotic chronic liver disease (Group II) and 21 patients with benign structural or functional liver disease (Group III). Group I patients had significantly lower systolic (113.0 +/- 2.2 mm Hg, mean +/- S.E.) and diastolic (65.3 +/- 1.7 mm Hg) pressures than Group II patients (125.8 +/- 3.5 and 76.6 +/- 1.5 mm Hg, respectively (p less than 0.0001) or Group III patients (125.1 +/- 3.4 and 77.5 +/- 2.4 mm Hg, respectively) (p less than 0.0001). Serum levels of GABA, a potent amino acid neurotransmitter with known vasodilatory effects in vitro, were higher in Group I patients (1.12 +/- 0.26 microM, mean +/- S.E.) than in Group II patients (0.41 +/- 0.05 microM) (p less than 0.005) or Group III patients (0.34 +/- 0.03 mM) (p less than 0.05). A constant infusion of GABA into the systemic circulation of six adult dogs, at rates required to achieve serum GABA levels within one order of magnitude of those observed in humans with cirrhosis, resulted in a 17.0 +/- 4.3 mm Hg decrease in systolic pressure (p less than 0.05) and a 10.8 +/- 3.7 mm Hg decrease in diastolic pressure (p less than 0.05). Control amino acids were not vasoactive. The results of this study suggest that, in addition to other vasoactive compounds, a GABA-mediated process might contribute to the hypotension observed in patients with compensated cirrhosis.
NOTES OF AN EXPERIENCE OF STOVAIN AS A SPINAL ANALGESIC IN 100 CASES
Authors: J. H. Pringle
Journal: BMJ (1907)

STGYALI AS A STINA1L ANALGESIW.[JULY 6, I9C7.matted together as to be almost unrecognizable, but a posterior gastro.jejunostomywas performed, with a result as splendid as can be found anywhere in the annals of eurgery.
Dual IGF-1R/InsR Inhibitor BMS-754807 Synergizes with Hormonal Agents in Treatment of Estrogen-Dependent Breast Cancer
Authors: Xiaonan Hou, Fei Huang, Luciana F. Macedo, Sean C. Harrington, Karen A. Reeves, Ann Greer, Friedrich Graf Finckenstein, Angela Brodie, Marco M. Gottardis, Joan M. Carboni, Paul Haluska
Journal: Cancer Research (2011)

Abstract Insulin-like growth factor (IGF) signaling has been implicated in the resistance to hormonal therapy in breast cancer. Using a model of postmenopausal, estrogen-dependent breast cancer, we investigated the antitumor effects of the dual IGF-1R/InsR tyrosine kinase inhibitor BMS-754807 alone and in combination with letrozole or tamoxifen. BMS-754807 exhibited antiproliferative effects in vitro that synergized strongly in combination with letrozole or 4-hydroxytamoxifen and fulvestrant. Similarly, combined treatment of BMS-754807 with either tamoxifen or letrozole in vivo elicited tumor regressions not achieved by single-agent therapy. Notably, hormonal therapy enhanced the inhibition of IGF-1R/InsR without major side effects in animals. Microarray expression analysis revealed downregulation of cell-cycle control and survival pathways and upregulation of erbB in response to BMS-754807 plus hormonal therapy, particularly tamoxifen. Overall, these results offer a preclinical proof-of-concept for BMS-754807 as an antitumor agent in combination with hormonal therapies in hormone-sensitive breast cancer. Cooperative cell-cycle arrest, decreased proliferation, and enhanced promotion of apoptosis may contribute to antitumor effects to be gauged in future clinical investigations justified by our findings. Cancer Res; 71(24); 7597–607. ©2011 AACR.
Chenodiol (Chenodeoxycholic Acid) for Dissolution of Gallstones: The National Cooperative Gallstone Study
Authors: L J Schoenfield, J M Lachin
Journal: Annals of Internal Medicine (1981)

A double-masked study was conducted to determine the efficacy and safety of randomly allocated chenodiol (chenodeoxycholic acid, 750 mg/d or 350 mg/d) or placebo administered for 2 years to 916 patients for dissolution of radiolucent gallstones. There was confirmed complete dissolution in 13.5% of patients (750 mg/d), 5.2% (375 mg/d), and 0.8% (placebo), p < 0.0001. Partial (over 50%) or complete dissolution (by validated roentgenographic metrology) occurred in 40.8% (750 mg/d), 23.6% (375 mg/d), and 11.0% (placebo), p < 0.0001. Dissolution occurred more frequently in women, thin patients, or patients with small or floating gallstones or serum cholesterol ≥ 227 mg/dL. Clinically significant hepatotoxicity occurred in 3% of patients (750 mg/d), 0.4% (375 mg/d), and 0.4% (placebo), p < 0.007, and always was reversible biochemically. Elevations of 10% or more of serum cholesterol, mostly low-density lipoproteins, occurred in 85.2% of patients (750 mg/d), 82.8% (375 mg/d), and 67.0% (placebo), p < 0.001. Chenodiol, 750 mg/d for up to 2 years, is appropriate therapy for dissolution of gallstones in selected patients who are informed of the risks and benefits.
Bernheim's Syndrome: Report of a Case
Authors: DONALD H. ATLAS, HERMAN L. EISENBERG, PETER GABERMAN
Journal: Circulation (1950)

In the controversial Bernheim's syndrome, right ventricular failure can be produced by hypertrophy and dilatation of the left ventricle with encroachment of the intraventricular septum into the cavity of the right ventricle, forming a barrier to the flow of blood into the right ventricle. A case is reported in which this syndrome was diagnosed during life and confirmed at autopsy. Hearts of similar weight with left ventricular hypertrophy were sectioned in the same plane for comparative purposes.
An updated Asia Pacific Consensus Recommendations on colorectal cancer screening
Authors: J J Y Sung, S C Ng, F K L Chan, H M Chiu, H S Kim, T Matsuda, S S M Ng, J Y W Lau, S Zheng, S Adler, N Reddy, K G Yeoh, K K F Tsoi, J Y L Ching, E J Kuipers, L Rabeneck, G P Young, R J Steele, D Lieberman, K L Goh
Journal: Gut (2014)

<h3>Objective</h3> Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. <h3>Design</h3> Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. <h3>Results</h3> Age range for CRC screening is defined as 50–75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. <h3>Conclusions</h3> Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.
Accuracy of Capsule Colonoscopy and Computed Tomographic Colonography in Individuals With Positive Results From the Fecal Occult Blood Test
Authors: Emanuele Rondonotti, Claudia Borghi, Giovanna Mandelli, Franco Radaelli, Silvia Paggi, Arnaldo Amato, Gianni Imperiali, Natalia Terreni, Nicoletta Lenoci, Vittorio Terruzzi, Alessandra Baccarin, Alberto Martegani, Giancarlo Spinzi
Journal: Clinical Gastroenterology and Hepatology (2014)
Docetaxel-related peripheral neuropathy is a dose-dependent event; a retrospective study in a Greek population with NSCLC
Authors: Alexandros Kavvadias, Ioannis Gkiozos, Panagiotis Boulas, Georgios Tsoukalas, Konstantinos Syrigos
Journal: European Respiratory Journal (2012)

INTRODUCTION: Neurotoxicity is the most important non-hematologic toxicity of taxanes. It presents as peripheral neuropathy with tingling, numbness and pain with a “glove and stocking” distribution and influences the daily activities of patients treated with taxanes.  AIM: To record peripheral neuropathy in relation with the dosage of docetaxel in NSCLC.  METHOD: We retrospectively studied 700 consecutive files of patients from the archive of the oncology unit of our institution in treatment from December 2006 until May 2008. Election criteria includes patients with NSCLC, PS 0-2, any stage, treated with docetaxel in any combination. We evaluated peripheral neuropathy with CTCAEv3.0  RESULTS: We found 105 patients,84 males(80%),21 females(20%), median age 62.94±9.29, smokers 95(90,5%), median dose of docetaxel 74,42±7,88mg/m2, median aggregate dose 427,17±282,9mg, dose intensity 32,63±5,88mg/m2/week, median treatment duration 12,6±7,99weeks. Peripheral neuropathy presented in 28 (26,7%) patients, mild or moderate gravity, mainly sensory neuropathy in 75%, after 2,64±1,68 cycles. The group of patients who received docetaxel ≥ 80mg/m2 presented neuropathy at 37,5% versus 21,9%(P=0,09). The group with dose intensity ≥37,5mg/m2/week presented neuropathy at 47,1% versus 16,9%(P=0,001). In the group of aggregate load dose ≥600 mg, 51,6% presented neuropathy versus 16,4% with   CONCLUSION: Peripheral neuropathy is a dose-dependent adverse event that increases with the accumulation and the dose intensity of docetaxel. Symptoms usually resolve after treatment or by decreasing the dosage.
Patchiness and duodenal-jejunal variation of the mucosal abnormality in coeliac disease and dermatitis herpetiformis.
Authors: B B Scott, M S Losowsky
Journal: Gut (1976)

The incidence and degree of patchiness of mucosal abnormality in both coeliac disease (CD) and dermatitis herpetiformis (DH) is documented. As judged by both stereomicroscopy and subjective histology, patchiness occurred frequently in both CDand DH patients. In most cases the difference of abnormality was of only one grade, but in approximately 25% as assessed by stereomicroscopy and 10% as assessed by histology the difference was of two or more grades. In control subjects with normal small bowel mucosa the variation of the mucosal appearance between the duodenum and proximal jejunum was studied. Contrary to popular belief, no significant difference of villous and crypt measurements or of apparent villous "bridging" and "branching" between these two sites was found, if only well-orientated sections were studied. The stereomicroscopic appearances were also similar at these two sites, although villi tended to be broader in the duodenal biopsies. The duodenal-jejunal variation was also studied in CD and DH patients and although by both stereomicroscopy and subjective histology the appearances were similar in most patients, in approximately 33% the duodenal abnormality was the most severe and, surprisingly, the jejunal abnormality was more severe in approximately 15%. It is concluded that multiple, precisely located biopsies of both the duodenum and proximal jejunum are invaluable in the investigation of small bowel disease and in assessing response to treatment.
Distinct receptors and signaling pathways in alpha-thrombin- and thrombin receptor peptide-induced vascular contractions.
Authors: B Tesfamariam
Journal: Circulation Research (1994)

The vasoactive mechanisms of the serine protease alpha-thrombin were examined in isolated coronary arteries from dogs. In resting coronary arteries with endothelium, alpha-thrombin caused concentration-dependent contractions that were characterized by an initial transient relaxation followed by slowly developing sustained contractions. The vascular actions of alpha-thrombin were mimicked by the thrombin receptor-activating peptide (TRAP) SFLLRNP, a synthetic peptide based on the cleaved terminus of the thrombin receptor domain. Treatment of the arteries with N omega-nitro-L-arginine or removal of endothelium abolished the transient relaxations and enhanced the contractions, indicating that the transient relaxations were mediated by the concurrent release of endothelium-derived nitric oxide. alpha-Thrombin that had been catalytically inactivated with the irreversible inhibitor by use of D-Phe-Pro-Arg-chloromethyl ketone did not cause contractions, indicating the requirement of proteolytic cleavage by alpha-thrombin to induce contractions. In contrast to TRAP, alpha-thrombin-induced contractions were blocked by hirudin (a specific thrombin inhibitor), nifedipine and diltiazem (Ca2+ channel blockers), or staurosporine and calphostin C (protein kinase C inhibitors). Unlike alpha-thrombin, which undergoes homologous desensitization, TRAP failed to cause desensitization to subsequent stimulation by alpha-thrombin or TRAP. These observations support the hypothesis that vasoactive actions of alpha-thrombin are mediated by a mechanism that involves cleavage at the active site to expose a new NH2 terminus that activates the thrombin receptor. Further, the dissociation between alpha-thrombin and the synthetic receptor peptide in signal transduction and dissimilar desensitizing properties suggest the existence of distinct thrombin receptor subtypes and/or signaling events in vascular smooth muscle.
Do Not Count Out External-Beam Radiation Therapy for High-Risk Prostate Cancer
Authors: Daniel A. Hamstra, Jeff M. Michalski, Mack Roach, Howard M. Sandler
Journal: Journal of Clinical Oncology (2010)

Cancer: A Comparison of Clinical Cohorts Adjusted for Case Mix" by Zelefsky et al. 1 The authors analyzed 1,318 patients after primary radical prostatectomy and 1,062 patients after primary radiation therapy (RT) between 1992 and 2002.Surgery was performed by one of two experienced surgeons at either the Memorial Sloan-Kettering Cancer Center or Baylor College of Medicine, and RT was delivered at Memorial Sloan-Kettering Cancer Center to Ն 81 Gy using external-beam RT (EBRT).Of note, RT patients received at most short-term androgen-deprivation therapy (STAD), and no patients received long-term androgen-deprivation therapy (LTAD).In addition, no patients had RT to the pelvic lymph nodes.Not surprisingly pretreatment risk factors were significantly greater in the RT group compared with the surgical group, including higher prostate-specific antigen (PSA), higher clinical stage (cT3, 9% v 4%, respectively), higher Gleason scores (Gleason score of 8 to 10, 13% v 4%, respectively), and a lower likelihood of remaining disease free based on the preoperative Kattan nomogram (all P Ͻ .001).Therefore, it also was not surprising that there was a slightly higher rate of metastasis at 8 years in patients treated with RT than in patients treated with a primary surgical treatment (7% v 3%, respectively).The authors subsequently attempted to adjust for pretreatment characteristics and concluded that there were minimal differences in metastasis between treatment modalities in patients with low-risk disease but that in those with intermediate-and high-risk prostate cancer by National Comprehensive Cancer Network criteria, treatment with RT was associated with a 3.3% and 7.8% increased risk, respectively, of metastatic disease compared with primary surgical treatment.The authors do mention several limitations of their study, which all bias against the RT outcomes, including the lack of any adjuvant therapy in the RT group but judicious (albeit limited) use of adjuvant therapy in the surgery group, the lack of pelvic lymph node RT (but the use of extensive pelvic dissections in the high-risk surgical group), the lower rate of salvage treatment in the RT cohort compared with those treated with surgery (43% v 76%, respectively), and the longer delay to salvage treatment in the RT cohort compared with those treated with surgery (69 v 13 months, respectively).Any one of these factors could potentially explain the differences in outcome.Nevertheless, for highrisk prostate cancer, the authors went on to advocate that either surgery followed by planned adjuvant RT or combined EBRT and brachytherapy would be the preferred treatment compared with EBRT plus STAD.How do these conclusions compare with the published literature?It certainly is worth pointing out that the two treatments that the authors propose have never been demonstrated to be superior to the
Critical Role of the Carboxyl Terminus of Proline-rich Tyrosine Kinase (Pyk2) in the Activation of Human Neutrophils by Tumor Necrosis Factor
Authors: Hyunsil Han, Michele Fuortes, Carl Nathan
Journal: The Journal of Experimental Medicine (2002)

Transduction of Tat-tagged fusion proteins confirmed a hypothesis based on pharmacologic inhibitors (Fuortes, M., M. Melchior, H. Han, G.J. Lyon, and C. Nathan. 1999. J. Clin. Invest. 104:327-335) that proline-rich tyrosine kinase (Pyk2) plays a critical role in the activation of adherent human neutrophils, and allowed an analysis of individual Pyk2 domains not possible with chemical inhibitors. Acting as a dominant negative, the COOH terminus of Pyk2 fused to a Tat peptide (Tat-CT), but not other regions of Pyk2, specifically inhibited the respiratory burst of cells responding to tumor necrosis factor (TNF), Salmonella, or Listeria, while sparing responses induced by phorbol ester. Tat-CT suppressed TNF-triggered cell spreading and the phosphorylation of endogenous Pyk2 and the associated tyrosine kinase Syk without blocking the ability of neutrophils to degranulate and kill bacteria. Thus, separate signals control the respiratory burst and degranulation, and a normal rate of killing of some bacteria can be sustained by granule products in conjunction with a minimal residual respiratory burst. Inhibition of select inflammatory functions without impairment of antibacterial activity may commend the Pyk2 pathway as a potential target for antiinflammatory therapy.
Enthesopathy and tendinopathy in gout: computed tomographic assessment.
Authors: J C Gerster, M Landry, G Rappoport, G Rivier, B Duvoisin, P Schnyder
Journal: Annals of the Rheumatic Diseases (1996)

OBJECTIVE: To establish if computed tomography (CT) imaging, which has proved helpful in detecting intra-articular tophi in gout, can also be used to document gouty enthesopathy and tendinopathy. METHODS: Three patients with tophaceous gout and clinical involvement of the Achilles tendon (two cases) or patellar tendon (one case) were assessed with CT examination and plain radiographs. RESULTS: In the first two cases, CT images revealed linear or nodular high attenuation opacities within the substance of the Achilles tendons and their calcaneal insertion. In case 3, dense linear opacities were seen within the patellar tendon and within its tibial insertion. No such opacities of the tendons and entheses were seen on standard radiographs of these patients. CONCLUSIONS: CT appears to be the imaging method of choice for demonstrating monosodium urate deposits in entheses and tendons in tophaceous gout.
Temporal Validation of the UKPDS Outcomes Model Using 10-Year Posttrial Monitoring Data
Authors: Jose Leal, Alison J. Hayes, Alastair M. Gray, Rury R. Holman, Philip M. Clarke
Journal: Diabetes Care (2012)

OBJECTIVE To evaluate the accuracy of the UK Prospective Diabetes Study Outcomes Model (UKPDS-OM) in predicting clinical outcomes during the UKPDS posttrial monitoring (PTM) period. RESEARCH DESIGN AND METHODS At trial end in 1997, the 4,031 surviving UKPDS patients, of the 5,102 originally enrolled in the study, returned to their usual care providers, with no attempts made to maintain them in their randomized therapy groups. PTM risk factor data were collected for 5 years and clinical outcome data for 10 years. The UKPDS-OM was used firstly to forecast likely progression of HbA1c, systolic blood pressure, total-to-HDL cholesterol ratio, and smoking status and secondly to estimate the likely first occurrence of seven major diabetes-related complications or death from any cause. Model predictions were compared against observed PTM data for risk factor time paths and survival probabilities for major diabetes complications. RESULTS UKPDS-OM–forecasted risk factor time paths were similar to those observed for HbA1c (up to 3 years) and total-to-HDL cholesterol ratio but underestimated for systolic blood pressure and smoking status. Predicted 10-year event probabilities were similar to those observed for blindness, ischemic heart disease, myocardial infarction, and renal failure but were higher for heart failure and death from any cause and lower for stroke and amputation. CONCLUSIONS The UKPDS-OM has good predictive accuracy for two of four risk factor time paths and for 10-year clinical outcome probabilities with the exception of stroke, amputation, heart failure, and death from any cause. An updated version of the model incorporating PTM data is being developed.
Football and doping: study of African amateur footballers
Authors: P F M Ama, B Betnga, V J Ama Moor, J P Kamga
Journal: British Journal of Sports Medicine (2003)

To investigate use and awareness of lawful and unlawful substances by amateur footballers in Yaounde, Cameroon.A total of 1116 amateur footballers (1037 male and 79 female) out of 1500 contacted participated in this study. They were divided into three groups: elite players (n = 314); local players (n = 723); female players (n = 79). They answered a questionnaire of 30 items grouped under six main topics: identification of players; use of lawful substances subject to certain restrictions on the International Olympic Committee (IOC) list; use of IOC banned substances; doping behaviour; awareness of doping; food supplements. The results of the questionnaire were scrutinised using Microstat software, and the level of significance was p<0.05.(a) Use by our footballers of a banned substance (cocaine) and substances subject to certain restrictions (alcoholic drinks, methylated spirits, and banga (marijuana)). (b) Doping behaviour: use by our footballers of substances with similar effects to some IOC banned substances but not listed as such: tobacco, liboga, wie-wie (narcotic), bilibili (locally made alcohol drink). (c) A large intake of vitamin C (food supplements) in all three groups. In contrast, the footballers' knowledge of doping was vague.Preventive actions and an epidemiological study of doping among footballers are urgently required.
Noninvasive cardiac output measurements in patients with pulmonary hypertension
Authors: Jonathan D. Rich, Stephen L. Archer, Stuart Rich
Journal: European Respiratory Journal (2012)

Pulmonary hypertension (PH) is characterised by a progressive decline in cardiac output (CO) and right heart failure. NICOM® (noninvasive cardiac output monitor) is a bioreactance-based technology that has been broadly validated, but its specific application in right heart failure and PH is unknown. Cardiac catheterisation was performed in 50 consecutive patients with PH. CO measurements were performed using three different methods (thermodilution, Fick and NICOM) at baseline and after vasodilator challenge. We compared the precision (coefficient of variation) and accuracy of NICOM compared to thermodilution and Fick. The mean CO (L·min(-1)) at baseline as measured by the three methods was 4.73±1.15 (NICOM), 5.69±1.74 (thermodilution) and 4.84±1.39 (Fick). CO measured by NICOM was more precise than by thermodilution (3.5±0.3% versus 9.6±6.1%, p<0.001). Bland-Altman analyses comparing NICOM to thermodilution and Fick revealed bias and 95% limits of agreement that were comparable to those comparing Fick to thermodilution. All three CO methods detected an increase in CO in response to vasodilator challenge. CO measured via NICOM is precise and reliably measures CO at rest and changes in CO with vasodilator challenge in patients with PH. NICOM may allow for the noninvasive haemodynamic assessment of patients with PH and their response to therapy.