tbuckley/cabot-search huggingface dataset:
DANGERS OF THE IODIN TREATMENT IN EXOPHTHALMIC GOITER
Authors: C. E. de M. Sajous
Journal: JAMA (1924)

<h3>To the Editor:</h3> —In the editorial entitled "A Fortunate Therapeutic Error" (The Journal, October 18, p. 1249), you refer to the beneficial though accidental use by Trousseau of iodin in exophthalmic goiter, to Plummer and his associates at the Mayo Clinic, and also to the group of clinicians at the Massachusetts General Hospital who favor this method of treatment. Experience has taught me that iodin should be used with extreme circumspection in such cases. During the forty-six years that I have been in practice, never have I seen so many cases in which this "somewhat empiric procedure," as you rightly term it, would have, if continued, greatly compromised the issue and life itself. It has been my lot to see several such cases within the last month. In one of these, 30 drops of compound solution of iodin was being given daily by the family physician. The patient going from
BAZ2A (TIP5) is involved in epigenetic alterations in prostate cancer and its overexpression predicts disease recurrence
Authors: Lei Gu, Sandra C Frommel, Christopher C Oakes, Ronald Simon, Katharina Grupp, Cristina Y Gerig, Dominik Bär, Mark D Robinson, Constance Baer, Melanie Weiss, Zuguang Gu, Matthieu Schapira, Ruprecht Kuner, Holger Sültmann, Maurizio Provenzano, Marie-Laure Yaspo, Benedikt Brors, Jan Korbel, Thorsten Schlomm, Guido Sauter, Roland Eils, Christoph Plass, Raffaella Santoro
Journal: Nature Genetics (2014)
Brain Elimination Half-Life of Fluvoxamine Measured by <sup>19</sup>F Magnetic Resonance Spectroscopy
Authors: Wayne L. Strauss, Matthew E. Layton, Stephen R. Dager
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: This study used fluorine-19 magnetic resonance spectroscopy (19F MRS) to characterize the elimination of fluvoxamine from the human brain after abrupt drug discontinuation. The elimination half-lives of fluvoxamine in brain and plasma were determined to assess their interdependence and the relationship of brain half-life to the clinical practice of drug holidays and reports of acute withdrawal symptoms. METHOD: Six subjects completing clinical treatment with fluvoxamine were enrolled in the study. Spectroscopic quantification of whole brain fluvoxamine concentrations and chromatographic determination of plasma fluvoxamine levels were performed serially for up to 10 days after drug withdrawal. Psychiatric evaluation to assess withdrawal symptoms was also done at each scanning session. RESULTS: Elimination of fluvoxamine in the brain and plasma was optimally described by first-order kinetics; the mean elimination half-lives were 58 hours and 26 hours, respectively. The mean ratio of fluvoxamine brain elimination half-life to plasma half-life was 2.4. Three of the six subjects experienced mild to moderate withdrawal symptoms between the third and fifth days of the study, which corresponded to between one and two brain half-lives of fluvoxamine. CONCLUSIONS: The brain elimination half-life for fluorinated psychotropic compounds can be measured noninvasively by 19F MRS. The elimination half-life of fluvoxamine was found to be substantially longer for the brain than for plasma. The time course of withdrawal symptom onset and the rationale for drug holidays with fluvoxamine appear to be well explained by the brain elimination half-life.
712. AAV-Mediated Allele-Specific RNA Interference of a Common Dominant Rhodopsin Mutation Causing Retinitis Pigmentosa
Authors: Alessandra Tessitore, Fabiana Parisi, Mariacarmela Allocca, Umberto Di Vicino, Michela A. Denti, Luciano Domenici, Irene Bozzoni, Alberto Auricchio
Journal: Molecular Therapy (2006)

Inherited retinal degenerations are a group of clinically and genetically heterogeneous diseases characterized by progressive photoreceptor cell death eventually leading to blindness and for which no therapies are available. Mutations in the rhodopsin gene are common causes of autosomal dominant retinitis pigmentosa (RP). Among them the P23H amino-acid substitution represents the most frequent rhodopsin mutation in US. Given the gain of function effect exerted by the P23H mutation, strategies aimed at silencing the expression of the mutated allele, like RNA interference, are desirable. We have designed five different small interfering RNAs (siRNA) to specifically silence the P23H rhodopsin allele expressed by a transgene rat model of the disease. Following transient transfection in 293 cells, we have selected one siRNA with strongest rhodopsin P23H silencing ability. To allow continuous siRNA production bypassing the limit of repeated administrations otherwise required to obtain long term therapeutic effects, we have developed an adeno- associated viral (AAV) vector expressing the short hairpin RNA (shRNA) based on the siRNA selected in vitro. We show in vitro the ability of the AAV-expressed shRNA to efficiently inhibit the expression of the P23H but not wild-type rhodopsin allele at both protein and RNA levels. Following administration of the AAV5 vector to the subretinal space of P23H transgenic rats, we show expression of the shRNA in the retina resulting in inhibition of rhodopsin P23H expression that is not able to prevent or inhibit photoreceptor degeneration. Since rhodopsin is the most abundant rod photoreceptor protein, systems resulting in more robust shRNA expression in the retina than the U1 small-nuclear RNA promoter or AAV serotype we used might be required to achieve therapeutic efficacy in vivo.
Efficacy and safety of transcatheter ablation of posteroseptal accessory pathways.
Authors: F Morady, M M Scheinman, S A Winston, L A DiCarlo, J C Davis, J C Griffin, M Ruder, J A Abbott, M Eldar
Journal: Circulation (1985)

Eight patients with a posteroseptal accessory pathway and symptomatic atrial fibrillation and/or orthodromic reciprocating tachycardia underwent attempted transcatheter ablation of the accessory pathway. A quadripolar electrode catheter was positioned within the coronary sinus such that the proximal pair of electrodes straddled the os. This proximal pair of electrodes was made electrically common and connected to the cathodal output of a defibrillator. A patch electrode placed over the midthoracic spine was connected to the anodal sink of the defibrillator. Two to three transcatheter shocks were delivered, with a cumulative energy of 600 to 900 J. Immediately after the shocks were delivered, retrograde accessory pathway conduction was absent in each patient. Anterograde conduction through the posteroseptal accessory pathway was absent in six patients. In one patient, retrograde accessory pathway conduction was absent and anterograde conduction was present but was slower than at baseline. In this patient, orthodromic tachycardia was no longer inducible and the ventricular rate during induced atrial fibrillation was 150 beats/min, compared with 220 beats/min before the attempted ablation. He has remained asymptomatic without antiarrhythmic drug therapy for 18 months. In one patient, the transcatheter shocks had no long-term effect on accessory pathway conduction. The shocks delivered at the os of the coronary sinus were well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
GASTROINTESTINAL WATER AND ELECTROLYTES. I. THE EQUILIBRATION OF RADIOSODIUM IN GASTROINTESTINAL CONTENTS AND THE PROPORTION OF EXCHANGEABLE SODIUM (Nae) IN THE GASTROINTESTINAL TRACT 1
Authors: I. S. Edelman, N. J. Sweet
Journal: Journal of Clinical Investigation (1956)

The concept of the partition of body water and electrolytes into two anatomical entities, extra- cellular and intracellular fluid, is well established.This is based on their fundamental differences in electrolyte structure (1).More refined definitions of water and electrolyte anatomy have become possible by the application of tracer dilution methods to in vivo estimation of body water and elec- trolyte content (2, 3).Thus, ideas on the organization of extracellular fluid have undergone dis- tinct evolution in recent years.It has been pointed out that the equilibration properties of sodium in bone and of inulin and thiosulfate in dense connective tissue distinguishes the extracellular phase of these tissues from free interstitial fluid (4, 5).The proposal has also been made that the term transcellular fluid be applied to those extracellular fluids which are not in simple diffusion equilibrium with plasma and are probably formed as a result of active cellular transport mechanisms (3).This would include fluid in the gastrointestinal tract, joint spaces, synovial sacs, cerebrospinal canal, anterior chamber of the eye, glandular ducts and acini, and in the renal tubules.The physiological significance of transcellular fluids will depend, in part, on the volume of these fluids and the extent of exchangeability of their individual components.This and the three articles to follow (6-8) will report the results of studies on the magnitude of intraluminal gastrointestinal water and electrolytes in rabbits and humans and on the equilibration of
Hepatic Function Before and After Resection of Liver
Authors: F. V. Flynn, J. M. Walshe
Journal: BMJ (1951)

It is well known that "liver-function tests" may be negative in the presence of extensive liver disease and that sometimes one.ofthese tests may be positive whilst others are negative.Recently the opportunity arose of investigating liver function in a patient before and after partial resection of the liver, and the findings are recorded as an indication of the effects of simple reduc- tion of liver tissue on these tests.In a survey of the literature recording partial hepatectomy in man we have It was at this stage that the initial pathological investigations were carried out.At a second operation for radical excision of the growth, also performed'by Mr. Riddell, under thiopentone, curare.and nitrou § oxide anaesthesia, the left lobe of the liver was removed by diathermy incision after ligation of the main vessels to the lobe.The excised portion of liver had a fresh weight of 215 g., and, like the organ as a whole, it showed no evidence of cirrhosis either macroscopically or microscopically.The remaining neoplastic, nodule had a diameter of 1 cm.During the immediate post-operative period, which was free from complications, the liver-function tests were all repeated.The patient has remained well and gained w,eight during the nine months since his operation.There has been some increase in the size of the right lobe of the liver, presumably as a result of compensatory hyperplasia.
Compliance with NAEPP asthma guidelines in a hospital based pediatric clinic and school based health clinics after an asthma education program
Authors: T. Tavarkiladze, S. Kearney, K. Garrett-Szymanski, A. Khadavi, Y. Persaud, W. Mak, R. Giusti, S. Watson, B. Silverman, A.T. Schneider
Journal: Journal of Allergy and Clinical Immunology (2005)
Abstract 570: Role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the cytotoxicity of the Hsp90 inhibitor 17AAG in human pancreatic cancer cells
Authors: Biehuoy Shieh, David Siegel, Chao Yan, Jadwiga K. Kepa, David Ross
Journal: Cancer Research (2010)

Abstract Previous work has demonstrated that NQO1 can reduce the benzoquinone ansamycin Hsp90 inhibitor 17-allyamino-demethoxy geldanamycin (17AAG) to the corresponding hydroquinone (17AAGH2). The formation of 17AAGH2 by NQO1 results in a more water soluble molecule and that binds with greater affinity to Hsp90 when compared to the parent quinone 17AAG. Experiments were conducted with the human pancreatic cancer cell line Panc1 which is homozygous for the NQO1*2 polymorphism and contains only trace levels of NQO1 protein and no NQO1 catalytic activity. An isogenic cell line expressing high levels of NQO1 (Panc1-C5) was generated by stable transfection of wild type NQO1 in Panc1 cells. 17AAG was more cytotoxic to Panc1-C5 cells with high levels of NQO1 when compared to NQO1-null parental Panc1 cells. Pretreatment of Panc1-C5 cells with the NQO1 mechanism-based inhibitor ES936 reduced the cytotoxicity of 17AAG to the level observed in Panc1 cells. No difference in the cytotoxicity of the non-quinone Hsp90 inhibitor radicicol was observed between the two cell lines Biomarkers of Hsp90 inhibition were measured in both Panc1 and Panc1-C5 cells following treatment with 17AAG. Higher protein levels of Hsp70 and lower amounts of cRaf, phosphorylated ERK1/2 and phosphylated MEK were observed in Panc1-C5 cells compared to Panc1 cells. In addition, cell cycle analysis revealed a greater number of Panc1-C5 cells arrested in G2M following 17AAG treatment compared to Panc1 cells. Cytotoxicity studies were also performed in additional human pancreatic cancer cell lines (BxPC3 and MiaPaCa2) that contain high levels of catalytically active NQO1*1 protein and in agreement with the studies described above the cytotoxicity of 17AAG could be reduced significantly following pretreatment with the NQO1 inhibitor ES936. The intracellular concentrations of 17AAG and 17AAH2 were measured in human pancreatic cancer cell lines and it was observed that greater amounts of both 17AAG and 17AAGH2 could be detected in cell lines with catalytically active NQO1 when compared to cells lacking NQO1 activity or cells pretreated with ES936. These data demonstrate that in addition to generating a more potent Hsp90 inhibitor (17AAGH2) the reduction of 17AAG to 17AAGH2 by NQO1 leads to significantly greater intracellular concentrations of 17AAG and 17AAGH2. These data confirm the role of NQO1 in sensitivity to 17AAG and suggest that genotyping for the NQO1*2 polymorphism should be considered in patients undergoing 17AAG treatment for pancreatic cancer or other solid tumors that are known to contain high levels of NQO1 activity (Supported by CA51210). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 570.
Prehospital thrombolysis: Beneficial effects of very early treatment on infarct size and left ventricular function
Authors: Thomas Linderer, Rolf Schröder, Richard Arntz, Marie-Luise Heineking, Werner Wunderlich, Kathrin Kohl, Florian Forycki, Rudolf Henzgen, Joachim Wagner
Journal: Journal of the American College of Cardiology (1993)
Expression of CD31/PECAM-1 (Platelet Endothelial Cell Adhesion Molecule 1) by Blastic Plasmacytoid Dendritic Cell Neoplasms
Authors: Katrin A. Salva, Anna K. Haemel, Laura B. Pincus, Jing Liu, Uma Sundram, Joan Guitart, B. Jack Longley, Gary S. Wood
Journal: JAMA Dermatology (2013)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare malignant neoplasm with cutaneous manifestations and a rapidly progressive clinical course. The diagnosis relies on characteristic clinicopathologic and immunopathologic features. However, the overlap of immunophenotypic features with other cancers, as well as newly discovered interpersonal and intrapersonal phenotypic variations, renders the identification of BPDCN challenging. A greater understanding of the proteins expressed by BPDCN might facilitate its recognition and provide insights into its clinical behavior.In 7 of 9 patients at 4 tertiary care institutions, immunohistochemical analysis demonstrated strong CD31/PECAM-1 (platelet endothelial cell adhesion molecule 1) expression by neoplastic cells. Combined with similar findings observed in 1 former patient, 8 of 10 cases of BPDCN were CD31/PECAM-1 positive.Expression of CD31/PECAM-1 by BPDCN adds new information about the antigenic profile of this unusual neoplasm. CD31/PECAM-1 influences multiple cell functions including adhesion, apoptosis, coagulation, host response, and protein synthesis that might affect clinical features of BPDCN such as hemorrhage, aggressive tumor growth, and resistance to therapy. Therefore, the potential role of this molecule in the tumor formation and progression of BPDCN warrants additional exploration.
The management of cirrhotic ascites
Authors: Gin-ho Lo
Journal: Hepatology (2009)

I read with interest the article relating to the management of cirrhotic ascites by Runyon published in HEPATOLOGY.1 This article has made a comprehensive, updated review regarding the treatment guidelines for ascites. However, I would like to make some comments. Recommendation 7 suggests that patients with cirrhosis who had ascites ascribed to alcoholism should abstain from alcohol consumption. Because lamivudine has proven to be beneficial in patients with severely decompensated cirrhosis or ascites,2, 3 institution of antiviral treatment should be recommended for patients with ascites due to hepatitis B virus. Recommendation 12 suggests that liver transplantation should be considered in patients with cirrhosis and ascites. Antiviral treatment of hepatitis B virus and abstinence of alcohol may reverse the underlying lesions of ascites, and thus, liver transplantation should be considered in patients with cirrhotic ascites which is not amenable to control. Recommendation 19 suggests that albumin infusion plus administration of vasoactive drugs such as octreotide and midodrine should be considered in the treatment of type 1 hepatorenal syndrome. The evidence is regarded as Class IIa and level B. Actually, albumin infusion plus terlipressin has proven to be effective to improve renal function in hepatorenal syndrome type 1 by randomized, controlled trial and meta-analysis.4, 5 Thus, the evidence of Recommendation 19 should be classified as Class I and level A. Gin-ho Lo M.D.*, * Department of Medical Education; Digestive Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
Tbx18 regulates the development of the ureteral mesenchyme
Authors: R. Airik
Journal: Journal of Clinical Investigation (2006)

Congenital malformations of the urinary tract are a major cause of renal failure in children and young adults. They are often caused by physical obstruction or by functional impairment of the peristaltic machinery of the ureter. The underlying molecular and cellular defects are, however, poorly understood. Here we present the phenotypic characterization of a new mouse model for congenital ureter malformation that revealed the molecular pathway important for the formation of the functional mesenchymal coating of the ureter. The gene encoding the T-box transcription factor Tbx18 was expressed in undifferentiated mesenchymal cells surrounding the distal ureter stalk. In Tbx18–/– mice, prospective ureteral mesenchymal cells largely dislocalized to the surface of the kidneys. The remaining ureteral mesenchymal cells showed reduced proliferation and failed to differentiate into smooth muscles, but instead became fibrous and ligamentous tissue. Absence of ureteral smooth muscles resulted in a short hydroureter and hydronephrosis at birth. Our analysis also showed that the ureteral mesenchyme derives from a distinct cell population that is separated early in kidney development from that of other mesenchymal cells of the renal system.
Acute hepatitis B in patients in Britain related to previous operations and dental treatment.
Authors: S Polakoff
Journal: BMJ (1986)

The frequency of transmission of hepatitis B virus infection from health service staff to patients was assessed from reports of confirmed cases of acute clinical hepatitis in 1980-3. During the four years 4505 reports (91% of the total) included replies to a question about recent operations; 153 patients (3.4%) had this history. Transfused blood or blood products were considered the source for 27 cases (0.06%). Eleven patients (0.02%) were infected in two clusters, both in cardiac surgery units; six were caused by a perfusion technician, who was a symptomless carrier, and five by a surgical registrar during the incubation period of an acute hepatitis B infection. The estimated average annual risk of a patient developing acute hepatitis B as part of a cluster caused by staff during surgical procedures was one in a million operations. For another 11 patients blood transfusion could not be excluded as a source. Where no association between surgery and hepatitis was found the incidence of a history, lay between 2.3 and 2.6%. The Hospital In-Patient Enquiry data showed that about 2.4% of the population had had operations in a six month period. These findings suggest that transmission of hepatitis B infection from staff to patients is rare in Britain and that the small risk could be eliminated by attention to measures to preserve asepsis and by immunising staff at risk.
Does prior restenosis identify patients with a higher restenosis rate when undergoing subsequent PTCA of a new lesion?
Authors: Stuart J. Bresse, Bruce A. Bergelson, Alice K. Jacobs, Caroline D. Melidossian, Gary R. Garber, Roger H. Hills, Nicholas A. Ruocco, Thomas J. Ryan, David P. Faxon
Journal: Journal of the American College of Cardiology (1990)
Abstract P4-07-12: miR-206 inhibits cell migration through direct targeting of the actin-binding protein coronin 1C in triple-negative breast cancer
Authors: J Wang, E Tsouko, P Jonsson, J Bergh, J Hartman, E Aydogdu, C Williams
Journal: Cancer Research (2013)

Abstract Patients with triple-negative breast cancer (TNBC) have an overall poor prognosis, which is primarily due to a high metastatic capacity of these tumors. Novel therapeutic approaches to target the signaling pathways that promote metastasis are desirable, in order to improve the outcome of TNBC patients. A loss of function of a microRNA, miR-206, is related to increased metastasis potential in breast cancers but the mechanism remains to be elucidated. In this study, we show that miR-206 was decreased in TNBC clinical tumor samples and cell lines whereas one of its predicted targets, actin-binding protein CORO1C, was increased. Expression of miR-206 significantly reduced proliferation by inducing a G1-S cell cycle arrest and migration and also repressed CORO1C mRNA and protein levels. We demonstrate that miR-206 interacts with the 3’-untranslated region (3’-UTR) of CORO1C and regulates this gene post-transcriptionally. Further, silencing of CORO1C reduced tumor cell migration and affected the actin skeleton and cell morphology, similar to miR-206 expression, but did not reduce proliferation. Our findings suggest that miR-206 targets CORO1C in TNBC cells, thereby affecting the actin filaments which results in a repressed tumor cell migration. This pathway is a novel mechanism offering a mechanistic basis whereby the metastatic potential of TNBC tumors could be targeted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-12.
Stephen Edward Smith
Authors: Caroline Richmond
Journal: BMJ (2008)

Stephen Smith, emeritus professor of applied pharmacology and therapeutics at St Thomas’s, made his reputation for his work on genetic responses to drugs and for the effects of drugs on the eye. His early research was concerned with individual differences in reactions to drugs, and he was one of the first people to undertake twin-based studies. Later, his work on the eye showed how the effects of drugs on the pupil could aid diagnosis of neuro-ophthalmological diseases.