tbuckley/cabot-search huggingface dataset:
A telephone hotline for transient ischaemic attack and stroke: prospective audit of a model to improve rapid access to specialist stroke care
Authors: E. Kerr, N. Arulraj, M. Scott, M. McDowall, M. v. Dijke, S. Keir, P. Sandercock, M. Dennis
Journal: BMJ (2010)

Patients with transient ischaemic attack or stroke benefit from early diagnosis, specialist assessment, and treatment with thrombolysis, and from stroke unit care and secondary prevention. The challenge with such patients is to minimise delays and ensure that treatment is appropriate, and to provide this care with the available resources.An ongoing prospective audit of a transient ischaemic attack and stroke clinic (1 January 2005 to 30 September 2009), as part of the Scottish Stroke Care Audit, and a three month targeted audit of immediate telephone access to a specialist stroke consultant (1 February 2009 to 30 April 2009).Stroke and transient ischaemic attack services in Lothian, a region of Scotland with a population of 810,000.Delays to assessment at a rapid access transient ischaemic attack and stroke clinic; delays to appropriate treatment.In February 2007 we introduced a 24 hours a day, seven days a week hotline to a consultant, who provided immediate advice on diagnosis, investigation, and emergency treatment for patients with transient ischaemic attack or stroke, and suggested the most appropriate care pathway, which might include an early appointment in a transient ischaemic attack and stroke clinic.The introduction of the hotline was associated with an immediate and sustained reduction in delays to assessment (from 13 to three days) and treatment. The proportion of participants taking statins at the time of visiting the clinic increased from 40% before the introduction of the hotline to 60% after the hotline was in place. Also, the hotline contributed to a reduction in the delay from last event to carotid surgery, from 58 days to 21.5 days. A total of 376 calls were received during the three month audit. Of the 273 (88%) referrers who responded to our questionnaire, 257 (94%) were very satisfied with the advice given over the hotline.Although associated with some disruption to the activities of the consultants, a 24 hours a day, seven days a week telephone hotline to a consultant is a feasible and effective means of reducing delays to specialist assessment and treatment of patients with transient ischaemic attack or stroke.
Alteration of Na+ homeostasis as a critical step in the development of irreversible hepatocyte injury after adenosine triphosphate depletion
Authors: Rita Carini, Giorgio Bellomo, Angelo Benedetti, Rosella Fulceri, Alessandra Gamberucci, Maurizio Parola, Mario U. Dianzani, Emanuele Albano
Journal: Hepatology (1995)

The exposure of isolated hepatocytes to the redox-cycling quinone menadione caused an early loss of mitochondrial membrane potential, adenosine triphosphate (ATP) depletion, and decreased intracellular pH. These alterations were followed by an increase in intracellular Na+ and, ultimately, cell death. If HCO3- was omitted from the incubation buffer, or the hepatocytes were incubated in an acidic medium (pH 6.5) the accumulation of Na+ was markedly reduced. Inhibition of the Na+/H+ exchanger and of the Na+/HCO3- cotransporter by, respectively, amiloride and 4,4'-di-isothiocyano-2,2'-disulfonic acid stilbene (DIDS) suppressed the initial Na+ influx but did not prevent subsequent Na+ accumulation, because amiloride and DIDS inhibited the Na+/K+ pump. The omission of HCO3- from the extracellular medium or the incubation in acidic conditions also prevented menadione toxicity, without interfering with the loss of mitochondrial membrane potential and with ATP depletion. A similar protection was evident when hepatocytes were incubated with menadione in a medium without Na+. The preservation of adequate levels of ATP by supplementing hepatocytes with fructose allowed the initial Na+ load to be recovered and provided partial protection against menadione toxicity. These effects were suppressed if Na+/K(+)-ATPase was inhibited with ouabain. Taken together, these results indicated that the activation of the Na+/HCO3- cotransporter and of the Na+/H+ exchanger in response to the decrease of intracellular pH stimulated an enhanced influx of Na+. When the activity of the Na+/K+ pump was not able to control Na+ levels because of ATP depletion, such an uncontrolled Na+ influx precipitated irreversible injury and caused hepatocyte death.
Diphenylhydantoin Suspension Hazard
Authors: Bill Butcher
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Dr. Lagos aptly describes a phenomenon that has plagued pharmacists for years, that being the proliferation of drug dosage forms and strengths that are of questionable or no clinical usefulness. However, I oppose Dr. Lagos' suggestion that diphenylhydantoin (Dilantin suspension) (125 mg/5 ml) be discontinued by the manufacturer. It enjoys some use in adult, hospitalized patients in whom the solid dosage form is not indicated. I agree that inadvertent dispensing of the stronger suspension for the weaker one may lead to intoxication, just as it would for many drugs available in different strengths. Obviously, the resolution of this problem lies in the continuing education of pharmacists and physicians (and manufacturers) that will help to inform them of these problems. Hospital pharmacists are continually challenged by orders for liquid preparations when none exist on the commercial market. It is no easy matter to formulate and prepare extemporaneous suspensions
Abstract 3151: High-throughput RNAi screening identifies a novel metastatic melanoma drug target in the context of PTEN mutation.
Authors: Holly Yin, Donald Chow, Chris Sereduk, Meraj Aziz, Seungchan Kim, Kevin M. Brown, Jeffrey M. Trent
Journal: Cancer Research (2013)

Abstract It has become increasingly important to identify targeted therapy in a defined molecular context. Here we will present our data which suggests TERT, a telomerase reverse transcriptase, serves as a novel drug target in melanoma in the context of PTEN mutation. PTEN is mutated in ∼15% of melanoma patients. Genomic RNA-interference (RNAi) technology was applied for synthetic lethality screens in an effort to identify the targets which upon knock-down significantly decrease cell viability specifically in the context of somatic mutations of the PTEN gene. We carried out such screen in a panel of 15 melanoma cell lines, including four PTEN mutated cell lines, against an siRNA library covering the kinome (∼700 genes with 4 siRNA per target) using CellTiter Glo as the endpoint to measure cell viability. Lethal genes, which decreased cell viability significantly upon knockdown, were initially identified for each cell line. Then the hit lists were compared between wild-type PTEN and mutant PTEN using a chi-square test, a statistical analysis. 29 gene candidates were selected for hit confirmation using the same set of siRNA, among which 24 genes were confirmed as potential PTEN synthetic lethal candidates, this results in a high confirmation rate of 83%. Based upon its association with melanoma risk (Law et al, J Invest Dermatol, 2012), We further validated TERT using a commercially available small molecule inhibitor. This inhibitor has significantly higherpotency in the PTEN mutant context (average IC50 of 0.34uM) compared to PTEN wild-type background (average IC50 of 0.75uM). This result both validates our RNAi screening results, but more importantly, this compound can serve as an initial structure scaffold for further optimization towards development as a novel drug for metastatic melanoma patients who carry PTEN mutations. Evaluation of more TERT inhibitors in a diverse panel of melanoma cell lines is presently underway. Citation Format: Holly Yin, Donald Chow, Chris Sereduk, Meraj Aziz, Seungchan Kim, Kevin M. Brown, Jeffrey M. Trent. High-throughput RNAi screening identifies a novel metastatic melanoma drug target in the context of PTEN mutation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3151. doi:10.1158/1538-7445.AM2013-3151
A CANNULA FOR USE IN THE TREATMENT OF SPONTANEOUS OR ACCIDENTAL PNEUMOTHORAX
Authors: I. A. Bigger
Journal: JAMA (1930)

In spontaneous or accidental pneumothorax with increased tension, it is frequently necessary to relieve the intrapleural pressure. In certain cases, aspiration suffices. In other cases, the air reaccumulates so rapidly that it is necessary to provide for its continuous escape. This is best accomplished by inserting an intercostal tube and using one-way valve drainage.  The cannula here illustrated was devised to replace the usual drainage tube. It is a silver tube 4 mm. in diameter and 4 cm. in length, with a flange near the outer end and perforations near the inner end. The flange has two slits, one on each side of the tube. The cannula is fitted with a steel trocar.  The length of the cannula projecting through the chest wall may be varied by placing different thicknesses of sterile gauze beneath the flange before it is inserted. Continuous escape of air is insured by perforations in the
Comparison of polymer scaffolds in rat spinal cord: A step toward quantitative assessment of combinatorial approaches to spinal cord repair
Authors: Bingkun K. Chen, Andrew M. Knight, Nicolas N. Madigan, LouAnn Gross, Mahrokh Dadsetan, Jarred J. Nesbitt, Gemma E. Rooney, Bradford L. Currier, Michael J. Yaszemski, Robert J. Spinner, Anthony J. Windebank
Journal: Biomaterials (2011)
Screening for Family and Intimate Partner Violence
Authors: Esta Soler, Jacquelyn Campbell
Journal: Annals of Internal Medicine (2004)

Letters6 July 2004Screening for Family and Intimate Partner ViolenceEsta Soler and Jacquelyn Campbell, RN, PhDEsta SolerFrom Family Violence Prevention Fund, San Francisco, CA 94103; and Johns Hopkins University School of Nursing, Baltimore, MD 21205.Search for more papers by this author and Jacquelyn Campbell, RN, PhDFrom Family Violence Prevention Fund, San Francisco, CA 94103; and Johns Hopkins University School of Nursing, Baltimore, MD 21205.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-1-200407060-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We are gratified that so many health care providers and leaders are rejecting the USPSTF's conclusion that there is insufficient evidence to recommend screening patients for domestic violence (1). Providers in every corner of the United States know from personal experience that screening for abuse can do a tremendous amount to help women and children who are experiencing family violence.The Task Force made serious mistakes in reaching its conclusion. It used an overly narrow approach by assessing screening for abuse as a medical screen rather than a behavioral assessment tool. It suggested that there are harms ...Reference1. Screening for family and intimate partner violence: recommendation statement. Ann Intern Med. 2004;140:382-6. [PMID: 14996680] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Family Violence Prevention Fund, San Francisco, CA 94103; and Johns Hopkins University School of Nursing, Baltimore, MD 21205. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoScreening for Family and Intimate Partner Violence: Recommendation StatementScreening for Family and Intimate Partner Violence Ned Calonge and Janet D. Allan Screening for Family and Intimate Partner Violence John C. Nelson and Carden Johnston Screening for Family and Intimate Partner Violence Christina Nicolaidis and Metrics Cited byTrauma Informed Care in MedicineIntimate partner violence“You Always End up Feeling Like You’re Some Hypochondriac”: Intimate Partner Violence Survivors’ Experiences Addressing Depression and PainInterpersonal and Intimate Partner ViolencePhysical and Sexual Violence During Pregnancy and After Delivery: A Prospective Multistate Study of Women With or at Risk for HIV Infection"Dissed" by Dating Violence 6 July 2004Volume 141, Issue 1Page: 82KeywordsChildrenDomestic violenceHealth care providersIntimate partner violencePregnancy ePublished: 6 July 2004 Issue Published: 6 July 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Naloxone Reversal of Pentazocine-Induced Respiratory Depression
Authors: Tamas Kallos
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Pentazocine lactate (Talwin Injectable) can produce respiratory depression when given in large doses or when given to susceptible patients. Naloxone hydrochloride (Narcan) is an antagonist for pentazocine, as well as narcotic analgesics. Pentazocine lactate has recently been introduced for the relief of pain in surgical, neurologic, obstetric, and medical disorders and as a supplement to surgical anesthesia. It is a member of the benzomorphan series and differs from other narcotic analgesics principally and importantly because of the absence of addiction liability.<sup>1</sup>It is consequently exempt from narcotic control regulations; thus it is likely to find widespread use for chronic pain problems. It is capable of producing respiratory depression when administered in large doses or to certain susceptible patients. The manufacturer's drug description<sup>2</sup>states that "the usual narcotic antagonists, such as nalorphine, are<i>not</i>effective respiratory stimulants for depression due to pentazocine lactate." Methylphenidate (Ritalin) is
GP who falsified research data found guilty of professional misconduct
Authors: O. Dyer
Journal: BMJ (2001)

A Glasgow general practitioner who admitted falsifying research data was found guilty of serious professional misconduct by the General Medical Council last week.

But an allegation that his actions had endangered the safety of patients was found not proved, and he has been allowed to remain on the medical register subject to certain conditions.

Dr Chaman Lal Anand, aged 70, was ordered to take no part in clinical trials for 12 months. He was also censured for …
Identification of a Second egfr Gene in Xiphophorus Uncovers an Expansion of the Epidermal Growth Factor Receptor Family in Fish
Authors: A. Gomez
Journal: Molecular Biology and Evolution (2003)

The epidermal growth factor receptor (EGFR) gives name to a family of receptors formed by four members in mammals (EGFR, ErbB2, ErbB3, and ErbB4). Members of this family can be activated to become potent oncogenes, and many human and animal tumors express qualitatively or quantitatively altered receptors from this group. We have isolated and characterized a second egfr gene in the melanoma model fish Xiphophorus. Both Xiphophorusegfra and egfrb duplicates are co-orthologs of the mammalian egfr gene. Database analysis showed that not only egfr but also erbB3 and erbB4 are present as duplicates in some fish species. They originated from ancient duplication events that might be consistent with the hypothesis of a fish-specific genome duplication. In Xiphophorus, the egfrb gene underwent a second duplication that generated the melanoma-inducing oncogene Xmrk. The study and comparison of some of the functional characteristics of both Xiphophorus EGF receptors, including expression profile, ligand-binding abilities, and intracellular signal transduction revealed that Xiphophorus Egfra not only shares common features with Egfrb and the human EGFR but also shows significant differences in its functional characteristics. The mechanism of maintenance of these duplicates remains to be clarified.
An Outbreak of Legionnaires' Disease Associated with a Contaminated Air-Conditioning Cooling Tower
Authors: Timothy J. Dondero, Robert C. Rendtorff, George F. Mallison, R. Mark Weeks, Joe S. Levy, Edward W. Wong, William Schaffner
Journal: New England Journal of Medicine (1980)

In August and September 1978, an outbreak of Legionnaires' disease occurred in Memphis, Tennessee. Of the 44 ill, 39 had been either patients, employees, visitors, or passers-by at one Memphis hospital (Hospital A) during the 10 days before. Assuming an incubation period of between two and 10 days, the onset of cases correlated precisely with the use of Hospital A's auxiliary air-conditioning cooling tower. L. pneumophila was recovered from two samples of water from the tower. Infection appeared to have occurred both outside and within the hospital. A significant association was demonstrated between acquisition of Legionnaires' disease and prior hospitalization in those areas of Hospital A that received ventilating air from air intakes near the auxiliary cooling tower. Tracer-smoke studies indicated that contaminated aerosols from the tower could easily reach these air intakes, as well as the street below, where four passers-by had been before they contracted Legionnaires' disease. This represents a common-source outbreak in which the source of L. pneumophila infection and airborne transmission were identified.
Abstract 5615: Global DNA methylation by LUMA predicts breast cancer risk in a population-based study
Authors: Xinran Xu, Marilie D. Gammon, James G. Wetmur, Susan L. Teiltelbaum, Patrick T. Bradshaw, Alfred I. Neugut, Regina M. Santella, Jia Chen
Journal: Cancer Research (2011)

Abstract Global methylation dysregulation is a hallmark of cancer cells. Global methylation measurement in peripheral blood may be a predictor of cancer risk and prognosis. In this study, we used two independent assays, LUminometric Methylation Assay (LUMA) and LINE-1 methylation by pyrosequencing, to assess the global methylation content in the peripheral blood DNA from the Long Island Breast Cancer Study Project, a population-based case-control study. We examined the association between global methylation levels and: 1) the risk of developing breast cancer among 1055 cases and 1101 controls using logistic regression models; 2) the risk of mortality among breast cancer cases using Cox proportional hazards models; and 3) one-carbon metabolism genetic polymorphisms and dietary intake among controls using ANOVA. LUMA methylation levels were higher among cases (mean: 57.3%) than among controls (mean: 52.4%; p&amp;lt;0.001). Compared to women in the lowest quintile of LUMA methylation, those in the highest quintile had a 2.41-fold increase in the risk of developing breast cancer (95% CI: 1.83-3.16; p for trend &amp;lt; 0.0001). Risk was strongest for in situ breast cancer (OR: 6.18; 95% CI: 3.34-11.43), although the estimate is based on small numbers; but the association did not vary by other tumor characteristics, life-style or several established breast cancer risk factors. Among cases, there was an indication that high LUMA levels were associated with reduced breast cancer-specific mortality. Among controls, LUMA levels were associated with two SNPs in the one-carbon metabolism pathway, MTHFR C677T (p=0.001) and MTRR A66G (p=0.018), but not with dietary intake of one-carbon related nutrients. No association was observed between LINE-1 methylation and breast cancer risk, breast cancer-specific mortality, one-carbon metabolism SNPs or nutrients, or LUMA methylation. Our results suggest that LUMA methylation levels in peripheral blood DNA are associated with breast cancer development and progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5615. doi:10.1158/1538-7445.AM2011-5615
Relationship between the Accumulation of Pituitary Growth Hormone and Nuclear Occupancy by Triiodothyronine in the Rat
Authors: Pierre Coulombe, Harold L. Schwartz, Jack H. Oppenheimer
Journal: Journal of Clinical Investigation (1978)

Studies were undertaken in hypothyroid rats in an effort to define the kinetics of growth hormone (GH) accumulation in response to i.v. pulse injections of triiodothyronine (T3) and to calculate the relationship between nuclear occupancy by T3 and the instantaneous rate of accumulation of pituitary GH. Results were contrasted to the findings in previous studies of the induction of hepatic mitochondrial α-glycerophosphate dehydrogenase (α-GPD) and malic enzyme (ME) by T3. The dose of T3 required to achieve half-maximal accumulation of GH in 24 h was 0.6 μg/100 g body wt, a value 15-fold less than the half-maximal dose for α-GPD and ME induction at a comparable time after injection. Although significant increase in pituitary GH were evident as early as 3 h after injection of maximally effective doses of T3, the rate of increase became linear only 12 h after injection. After achievement of peak values, the pituitary content of GH decayed with a similar terminal t½ of 3.9 days and 4.1 days in two groups of animals injected with a single dose of 1.0 and 50 μg T3/100 g body wt, respectively. In vivo isotopic displacement studies carried out at the equilibrium time point indicated that the pituitary nuclear binding capacity was 5.5 ng T3/g tissue and that the plasma concentration at which one-half of the nuclear sites are occupied is 1.0 ng/ml. Nuclear occupancy as a function of time was calculated from the estimated plasma T3 concentration after injection of the dose and the half-occupancy plasma concentration. These data were then analyzed by application of the mathematical model previously developed to ascertain the relationship between nuclear occupancy and the rate of hepatic enzyme induction. Results indicated that the pituitary nuclear occupancy-response relationship was generally linear, in marked contrast to the highly amplified relationship between nuclear occupancy and the response of ME and α-GPD to T3 in the liver. In supplementary experiments, euthyroid rats received daily injections of 200 μg of T3 for 7 days to keep nuclear sites nearly saturated for the duration of the experiment. No significant increase in the pituitary GH content above euthyroid base-line levels was noted. This also contrasts with the marked increase above euthyroid levels in α-GPD and ME observed in previous studies. Our findings suggest the existence of major differences between the specific mechanisms which lead to the induction of pituitary GH and the hepatic enzymes by T3.
Vitamin D and Calcium Hormones in Pregnancy
Authors: Rajiv Kumar, Wayne R. Cohen, Franklin H. Epstein
Journal: New England Journal of Medicine (1980)

There is no time of life, and there are few diseases, in which such massive shifts in calcium occur so regularly as during pregnancy. Fetal bone formation demands that 25 to 30 g of calcium be deposited in the fetal skeleton, almost all of it during the second half of gestation. To prepare for this process and for the losses of calcium that occur with lactation, maternal calcium accretion begins early in pregnancy. Well before the major fetal ossification of late pregnancy, intestinal absorption of calcium is enhanced in the mother and her bone mass increases, a unique event in . . .