tbuckley/cabot-search huggingface dataset:
Chemical Fallout: Current Research on Persistent Pesticides
Authors: William A. Thomas
Journal: JAMA (1969)

The published proceedings of most symposia are disappointing on several counts. Happily, this record of the 1968 Rochester Conference on Toxicity is not ill organized, outdated, overedited, or even underindexed. The 26 presentations range from specific research reports on pesticide toxicology to reviews on the consequences of our dependence on biocides. The discussants focus on organomercurial and chlorinatedhydrocarbon pesticides, all of which are biologically active, chemically stable, and physically mobile. These characteristics account for the universal contamination by DDT a mere quarter century after it became available commercially. The candid, often pointed, discussions following each paper and during two special sessions contribute greatly to the volume. Recurring subjects include the role of birds as sentinels of environmental poisoning, toxicological problems of pesticide synergisms, direct and indirect effects on nontarget organisms, pesticide-induced hormonal imbalances with attendant reduction in reproductive success, and the inadequacy of government to protect our environment as well
BRCC36 Is Essential for Ionizing Radiation–Induced BRCA1 Phosphorylation and Nuclear Foci Formation
Authors: Xiaowei Chen, Cletus A. Arciero, Chunrong Wang, Dominique Broccoli, Andrew K. Godwin
Journal: Cancer Research (2006)

We have previously reported the identification and characterization of a novel BRCA1/2 interacting protein complex, BRCC (BRCA1/2-containing complex). BRCC36, one of the proteins in BRCC, directly interacts with BRCA1, and regulates the ubiquitin E3 ligase activity of BRCC. Importantly, BRCC36 is aberrantly expressed in the vast majority of breast tumors, indicating a potential role in the pathogenesis of this disease. To further elucidate the functional consequence of abnormal BRCC36 expression in breast cancer, we have done in vivo silencing studies using small interfering RNAs targeting BRCC36 in breast cancer cell lines, i.e., MCF-7, ZR-75-1, and T47D. Knock-down of BRCC36 alone does not affect cell growth, but when combined with ionizing radiation (IR) exposure, it leads to an increase in the percentage of cells undergoing apoptosis when compared with the small interfering RNA control group in breast cancer cells. Immunoblot analysis shows that inhibition of BRCC36 has no effect on the activation of ATM, expression of p21 and p53, or BRCA1-BARD1 interaction following IR exposure. Importantly, BRCC36 depletion disrupts IR-induced phosphorylation of BRCA1. Immunofluorescent staining of BRCA1 and gamma-H2AX indicates that BRCC36 depletion prevents the formation of BRCA1 nuclear foci in response to DNA damage in breast cancer cells. These results show that down-regulation of BRCC36 expression impairs the DNA repair pathway activated in response to IR by inhibiting BRCA1 activation, thereby sensitizing breast cancer cells to IR-induced apoptosis.
Reserpine and Raynaud's Phenomenon
Authors: STEPHEN J. UMAN
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 December 1972Reserpine and Raynaud's PhenomenonSTEPHEN J. UMAN, M.D.STEPHEN J. UMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-77-6-1005_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The letter "Hematemesis After Reserpine for Raynaud's Phenomenon" by Drs. Sharon, Paolino, and Kaplan (Ann Intern Med 77:479, 1972) was of great interest to me.In 1971 I treated a patient with Raynaud's disease and gangrene of several fingertips with 1 mg of reserpine intra-arterially. He did not benefit from this procedure symptomatically, but 12 hours later he vomitted approximately 500 ml of bloody emesis. Roentgenologic examination showed no source for the bleeding, but it was presumed that an occult bleeding source had been uncovered by concurrent "desperation" treatment of his disorder with heparin anticoagulation. The letter... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1972Volume 77, Issue 6Page: 1005-1005KeywordsHemorrhageHeparinRaynaud syndromeReserpine Issue Published: 1 December 1972 PDF DownloadLoading ...
David John Rudman
Authors: David Honeybourne
Journal: BMJ (2006)

Paediatrician who became a pioneer in the management of cystic fibrosisTony Jackson made a considerable contribution to the transformation of cystic fibrosis from a fatal disease of infancy to a chronic disease of adults.He applied the developing technology and pharmaceutical developments to everyday practice, supported families and patients, and, after retirement, gave strategic direction to the Cystic Fibrosis Trust research and medical advisory committee, of which he was chairman.The trust awarded him its John Panchaud medal.
Sinusoidal efflux of glutathione in the perfused rat liver. Evidence for a carrier-mediated process.
Authors: M Ookhtens, K Hobdy, M C Corvasce, T Y Aw, N Kaplowitz
Journal: Journal of Clinical Investigation (1985)

Turnover of hepatic glutathione in vivo in the rat is almost entirely accounted for by cellular efflux, of which 80-90% is sinusoidal. Thus, sinusoidal efflux play a major quantitative role in homeostasis of hepatic glutathione. Som preliminary observations from our laboratory (1983. J. Pharmacol. Exp. Ther. 224:141-147.) and circumstantial evidence in the literature seemed to imply that the raising of the hepatic glutathione concentration above normal was not accompanied by a rise in the rate of sinusoidal efflux. Based on these observations, we hypothesized that the sinusoidal efflux was probably a saturable process and that at normal levels of hepatic glutathione the efflux behaved as a zero-order process (near-saturation). We tested our hypothesis by the use of isolated rat livers perfused in situ, single pass, with hemoglobin-free, oxygenated buffer medium at pH 7.4 and 37 degrees C. Preliminary experiments established a range of perfusion rates (3-4 ml/min per g) for adequacy of oxygenation, lack of cell injury, and minimization of variability contributed by perfusion rates. Hepatic glutathione was lowered to below normal by a 48-h fast, diethylmaleate (0.1-1.0 ml/kg i.p.), and buthionine sulfoximine (8 mmol/kg i.p.), and raised to above normal by 3-methylcholanthrene (20 mg/kg x 3 d i.p.) and cobalt chloride (0.05-0.27 g/kg-1 subcutaneously). Steady state sinusoidal efflux from each liver was measured over a 1-h perfusion, during which the coefficient of variation of glutathione in perfusates stayed within 10%. Hepatic glutathione efflux as a function of hepatic concentration was characterized by saturable kinetics with sigmoidal (non-hyperbolic) features. The data were fitted best with the Hill model and the following parameter values were estimated: Vmax = 20 nmol/min per g, Km = 3.2 mumol/g, and n = 3 binding/transport sites. The efflux could be inhibited reversibly by sulfobromophthalein-glutathione conjugate but was not affected by the addition of glutathione to the perfusion medium. The results support our hypothesis that sinusoidal efflux of glutathione is near saturation (approximately equal to 80% of Vmax) at normal (fed and fasted) liver glutathione concentrations. The phenomenon of saturability coupled with the ability to inhibit the efflux leads us to propose that sinusoidal efflux from hepatocytes appears to be a carrier-mediated process. Some recent studies by others, using sinusoidal membrane-enriched vesicles, also support these conclusions.
Report on the UICC workshops on breast cancer screening in premenopausal women in developed countries. Union Internationale Contre le Cancer
Authors: G. P. Murphy, N. Odartchenko
Journal: CA A Cancer Journal for Clinicians (1993)

At the recent UICC Meeting on Breast Cancer Screening in Premenopausal Women, three workshops were held to address issues concerning the evaluation of the efficacy of screening, current strategies in research and practice, and future directions in breast cancer control. The authors report on the results of these workshops, including a proposal for a multinational clinical study of breast cancer screening in premenopausal women.
THE NEPHELOMETER:AN INSTRUMENT FOR ESTIMATING THE NUMBER OF BACTERIA IN SUSPENSIONS USED FOR CALCULATING THE OPSONIC INDEX AND FOR VACCINES.
Authors: JOSEPH McFARLAND
Journal: JAMA (1907)

Those who have used the method of Leishman or the later method of Wright for estimating the phagocytic or opsonic indexes of the blood well know that it is essential to use bacterial suspensions containing uniform numbers of bacteria in order to secure uniformity of results. If the suspension used for one estimation contains twice as many bacteria as that used at another the results will vary, though not mathematically, according to the density of suspension. The method recommended by Wright is ingenious though cumbersome and depends on the actual enumeration of the bacteria contained in the suspension, and is accomplished by mixing a given volume of the bacterial suspension with an equal volume of blood, dropping a diaphragm with a small aperture into the eyepiece of the microscope, and then counting the number of blood corpuscles and bacteria in each of a number of microscopic fields. The computation that
REPRODUCIBILITY OF THREE-DIMENSIONAL BRAIN SPECT-MR IMAGE COREGISTRATION.
Authors: B. Roberts, J. Norenberg, J. Sanders, A. Koerner, L. Arata, M. Hartshorne
Journal: Clinical Nuclear Medicine (1999)

Scientific Abstracts And Posters From The 44Th Annual Meeting Of The Southwestern Chapter Of The Society Of Nuclear Medicine, And From The 12Th Northeastern Regional Scientific Meeting Of The New England And New York Chapters Of The Society Of Nuclear Medicine
PTU-029 The Use Of Endoclot™ Therapy In The Endoscopic Management Of Gastrointestinal Bleeding
Authors: J Patel, M Bhuva, I Al-Bakir, J Landy, S Beg, M Fullard, S Catnach, A Leahy
Journal: Gut (2014)

<h3>Introduction</h3> Endoclot™ is a non-toxic topical haemostatic powder consisting of absorbable modified polymers. We previously described our early experience using Endoclot™ as an adjunct haemostatic endoscopic therapy in 6 patients undergoing elective/emergency upper or lower gastrointestinal (GI) endoscopy.<sup>1 </sup>We now present the largest case series to date describing the use of Endoclot™ therapy in GI bleeding. <h3>Methods</h3> Endoclot™ was applied in upper GI bleed cases only when initial treatment with standard endoscopic dual therapies failed to achieve complete haemostasis. It was also applied to control bleeding post endoscopic mucosal resection (EMR) of rectal polyps. Endoclot™ was delivered by a dedicated applicator system onto bleeding areas. Successful Endoclot™ therapy was defined as achieving complete haemostasis during endoscopy, with no further bleeding within 30 days. <h3>Results</h3> Endoclot™ was utilised for 18 patients (11 men, 7 women, mean age 74; upper GI bleed n = 15, lower GI n = 3). Haemostasis was achieved in 16/18 (89%) patients. Endoclot™ was successful in 13 patients with an upper GI bleed: mallory-weiss tear (n = 2); gastric ulcer, all Forrest classification 1b (n = 2); duodenal ulcer, all Forrest classification 1b (n = 8); duodenal adenoma (n = 1). Prior haemostasis combinations used were: adrenaline injection with diathermy (n = 11); adrenaline injection with clips (n = 1); adrenaline injection, diathermy and clips (n = 1). Endoclot™ was successful in 3 patients with lower GI bleeding after EMR. Prior haemostasis used was argon plasma coagulation (n = 1). Endoclot™ therapy failed in 2 cases. In the first patient, haemostasis was achieved when Endoclot™ was applied to an originally suspected duodenal ulcer that continued to bleed despite adrenaline injection and diathermy. However, the patient developed melaena 2 days later, requiring repeat endoscopic therapy with adrenaline injection, clips and diathermy to regain haemostasis. Ensuing investigations showed an underlying gastrointestinal stromal tumour. The second patient had residual bleeding from a Dieulafoy lesion despite treatment with clips and sclerotherapy. Although Endoclot™ initially achieved haemostasis, the patient had melaena 3 days later. The recurrent bleed was controlled with adrenaline injection and banding of the bleeding vessel. <h3>Conclusion</h3> Endoclot™ is a potentially effective method of achieving haemostasis in GI bleeding when standard endoscopic therapies have failed. Anecdotally, in this series it was noted to be particularly useful to control oozing. Larger prospective controlled studies are required to further determine its exact role in upper and lower GI bleeding. <h3>Reference</h3> Halkerston K <i>et al</i>. Early clinical eExperience of endoclot™ in the treatment of acute gastro-intestinal bleeding. <i>Gut </i>2013;62:A149 <h3>Disclosure of Interest</h3> None Declared.
Clinical and Circulatory Effects of Isosorbide Dinitrate
Authors: ROBERT E. GOLDSTEIN, DOUGLAS R. ROSING, DAVID R. REDWOOD, G. DAVID BEISER, STEPHEN E. EPSTEIN
Journal: Circulation (1971)

In order to resolve current controversies on isosorbide dinitrate (ISDN), we employed a particularly sensitive testing protocol to evaluate effects of sublingual ISDN and nitroglycerin on the exercise capacity of patients with angina. Ten minutes after ISDN 21 of 23 patients exercised longer (average 2.7 minutes, P &lt; 0.001) than after placebo. Benefit was evident in only a minority of patients tested one hour and in none tested two hours after either ISDN or nitroglycerin. A given amount of exercise resulted in lower mean blood pressure (average 13 mm Hg, P &lt; 0.001), higher heart rate (average 10 beats/min, P &lt; 0.001), and shorter ejection time (average 0.04 second, P &lt; 0.001) after ISDN. Similar changes were seen after nitroglycerin. The product of blood pressure, heart rate, and ejection time, an index of myocardial O 2 consumption, was unchanged at angina after ISDN or nitroglycerin despite the increased exercise capacity, suggesting that clinical improvement after these drugs may be due to circulatory changes causing decreased myocardial O 2 demand. We conclude that sublingual ISDN closely resembles nitroglycerin in its alteration of circulatory responses to exercise and in the duration of the resultant improvement in exercise capacity.
Control of blood glucose during labour in diabetic women with combined glucose and low-dose insulin infusion.
Authors: T E West, C Lowy
Journal: BMJ (1977)

During 15 labours in diabetic women blood glucose concentrations were controlled with simultaneous infusion of insulin and glucose. The mean insulin infusion rate was between 1 and 2 U/h. No infant showed evidence of neonatal hypoglycaemia. The procedure is simple to use and may be carried out in any labour ward.
Procalcitonin (PCT) is useful in predicting the bacterial origin of an acute circulatory failure in critically ill patients
Authors: C. Cheval, J. F. Timsit, M. Garrouste-Orgeas, M. Assicot, B. De Jonghe, B. Misset, C. Bohuon, J. Carlet
Journal: Intensive Care Medicine (2000)
Proliferation of hepatic lineage cells of normal C57BL and interleukin-6 knockout mice after cocaine-induced periportal injury
Authors: David Rosenberg, Zoran Ilic, Li Yin, Stewart Sell
Journal: Hepatology (2000)

The cellular response to periportal liver injury, induced by phenobarbital feeding and cocaine injection, is used to compare the restitutive proliferation of hepatocytes, cholangiocytes, and oval cells in the livers of normal control to those of interleukin-6 (IL-6) knockout mice. After this injury hepatocytes in noninjured middle and central zones start to proliferate first, followed by proliferation of cholangiocytes and intraportal oval cells. Proliferation of all cell types peaks at 2 days, but oval cells continue to proliferate and differentiate through days 4 and 6 as they reconstitute the necrotic zone. By day 10, the injured zone is completely repaired, and no dividing cells remain. During the first 3 to 4 days after injury, the number of proliferating hepatocytes, cholangiocytes, and sinusoidal cells is lower in IL-6 knockout mice than in normal mice, whereas the number of dividing oval cells is higher. However, overall repair of the injury is accomplished in the same time period in both groups. During repair of the periportal zone, oval cells acquire differentiation markers of hepatocytes as they cross the zone of injury. In conclusion, the phenobarbital/cocaine injury model is useful to study restitutive proliferation of mouse liver cell lineages. The proliferative response in IL-6 knockout mice shows that IL-6 is not required for proliferation of liver cells; timely repair of liver injury occurs in both normal and IL-6 knockout mice. Increased proliferation of oval cells in IL-6 knockout mice may compensate for the lower proliferation of other liver cell types.
THE TREATMENT OF CANCER WITH COCAINE
Authors: R. M. Gilchrist
Journal: BMJ (1909)

SPE-7 anti-DNP-IgE initiates inflammatory cytokine production without antigen stimulation in vitro. In contrast, ϵ2624 anti-DNP IgE does not induce inflammatory cytokines independent of antigen-stimulation. However, their effects in vivo have not been described. We tested two well-characterized anti-mouse IgE antibody clones in our model of murine thermal hyperalgesia. We found pronounced hindpaw hyperalgesic responses lasting to at least 6 hours following antigen challenge after sensitization with SPE-7. These responses were accompanied by histamine release and neutrophil influx as we have previously shown in c48/80-mediated thermal hyperalgesia. In contrast, we found that antigen challenge following sensitization with clone ϵ2624 produced slight hyperalgesia at 1 hr that was resolved by 3 hours. We demonstrate a novel functional, behavioral difference between reactions mediated by these IgE antibody clones in vivo in mice. Also, SPE-7 does not lead to antigen-independent cytokine production in the mouse hind paw. After antigen challenge, both IgEs produce equivalent levels of TNF-α, IL-1, and IL-6, and cause equivalent histamine release and neutrophil influx. Thus tissue-resident sentinel mast cells may be critical initiators of allergen-evoked hyperalgesia in mice and differences in the nature and repertoire of IgE antibodies produced during an allergic response likely have pathophysiological implications for various health outcomes including pain.
How and why do we measure surgical risk?
Authors: Manish Chand, Tom Armstrong, Greg Britton, Guy F Nash
Journal: Journal of the Royal Society of Medicine (2007)

Surgical decision-making has evolved over time, and what was once an intuitive matter for surgeons has now become a multi-faceted decision with increased expectations from medical staff and patients, making the decision-making process itself often as challenging as the technical procedure.

When planning the most appropriate treatment for a patient, it is important to distinguish what we aim to achieve with regards to treating the pathology from what can be realistically expected from the patient physiologically. In other words, has the patient the potential to withstand the insult of the treatment itself and what are the risks involved? By quantifying this risk and making it a key part of surgical decision-making, we can arrive at the safest modality of treatment for an individual patient. This allows realistic expectations for the patient, helping them to make an informed decision.

This article aims to highlight some of the important aspects of surgical risk and the impact they have on patients.
Pharmacists and Drug Information
Authors: Craig Cooper
Journal: JAMA (1980)

To the Editor.—  We are disappointed with the article Survey of Health Professionals' Information Habits and Needs: Conducted Through Personal Interviews by Stinson and Mueller (243:140, 1980). We, as pharmacists, believe that we were neglected by the researchers in this publication. Pharmacists, particularly in the hospital setting, have become increasingly involved with drug information services in the past few decades. Pharmacists across the nation are active users and providers of drug information. It is uncommon to find a medical center today that does not have a pharmacy-based drug information service. Furthermore, the Drug Information Association, which is a national association of drug information providers, has a strong pharmacy constituency. As well as participating in founding this association, pharmacists are active members and have served as past residents.  Our pharmacy provides formalized drug information services to health care professionals within and outside of our hospital. Since it was established, our drug
Advances continue in sickle cell disease
Authors: B. Bolsen
Journal: JAMA (1982)

Despite the fact that sickle cell disease has long been understood at the molecular level, there is insufficient knowledge about the natural history of the disease, and preventive or curative treatment has not been found. The disease afflicts about 50,000 Americans, mostly black, and thousands of Africans, Arabs, Indians, Greeks, and Italians.  Investigators at a recent scientific meeting reported progress on several fronts: a low-risk method for prenatally detecting the disease in all cases; a look, for the first time, at the behavior of sickle hemoglobin inside human RBCs; a method of drug delivery designed to minimize toxic side effects; and an ongoing study to characterize the clinical course of the disease.  Prenatal Detection  Using a restriction enzyme that, like all such enzymes, always cuts DNA in the same place (in this case a certain location on the β-globin gene), investigators at the University of California, San Francisco, can now