tbuckley/cabot-search huggingface dataset:
Use of Spironolactone in Renal Edema
Authors: Robert T. Manning
Journal: JAMA (1961)

Spironolactone, an aldosterone-antagonist, was administered to 4 adults and 2 children in the treatment of refractory edema of renal origin. The 6 case histories presented show that an excellent response, indicated by loss of edema, was obtained in 5. Three of the adults with azotemia developed hyperkalemia, so that the spironolactone had to be withdrawn. One of these patients showed electrocardiographic signs of hyperkalemia. When spironolactone is used in patients with azotemia observation of serum potassium levels is considered mandatory. The drug does not alter the underlying disease process, but the authors consider it a useful adjunct in the treatment of patients refractory edema of renal origin, especially in children with the nephrotic syndrome.
Abstract 917: High antitumor activity of the ERK inhibitor SCH722984 against BRAF-mutant, NRAS-mutant and wild-type melanoma cell lines.
Authors: Deborah J. Wong, Lidia Robert, Mohammad S. Atefi, David Foulad, Earl V. Avramis, Begonya Comin-Anduix, Ahmed A. Samatar, Antoni Ribas
Journal: Cancer Research (2013)

Abstract MAPK pathway dysregulation via mutations in proteins such as BRAFV600E and NRASQ61 is a key feature in melanomas, leading to constitutive ERK signaling. Currently, there are no FDA-approved targeted therapies effective in vemurafenib-resistant BRAFV600E mutant, NRAS mutant, or wild-type melanoma. The effect of SCH722984, an allosteric inhibitor of ERK 1/2, was determined in a panel of 53 melanoma cell lines, including wild-type, NRAS-mutant and vemurafenib-sensitive and resistant BRAF-mutant melanoma. 54% (13 of 24) of BRAF mutants, including 4 with innate vemurafenib resistance, were sensitive to SCH722984 with an IC50 &amp;lt;1μM. 100% (3 of 3) of BRAF/NRAS double mutants, 71% (10 of 14) of NRAS mutants and 71% (5 of 7) of wild-type melanomas were sensitive. 13% (5 of 24) of BRAF mutants, 14% (2 of 14) of NRAS mutants and 29% (2 of 7) of wild-type melanomas were intermediately sensitive (IC50 1-1.5μM). Among BRAFV600E mutants with in vitro acquired resistance to vemurafenib, those with MAPK pathway reactivation as the mechanism of resistance were sensitive to SCH722984. Combining vemurafenib and SCH722984 in BRAF mutant melanoma was synergistic in a majority of cell lines, resulting in up to 10-fold decrease in the 50% inhibitory concentration (IC50) and with combination indices (CI) below 1. SCH722984 inhibited phosphorylation of RSK, an ERK downstream target. Finally, long term cultures of two BRAFV600E-mutant cell lines sensitive to SCH722984 showed that treatment with SCH722984 alone or in combination with vemurafenib was more potent than vemurafenib alone and resulted in a significant delay in developing acquired resistance. SCH722984 may therefore be clinically applicable as a treatment for non-BRAF mutant melanoma or in BRAF-mutant melanoma with innate or acquired resistance, alone or in combination with BRAF inhibitors. Citation Format: Deborah J. Wong, Lidia Robert, Mohammad S. Atefi, David Foulad, Earl V. Avramis, Begonya Comin-Anduix, Ahmed A. Samatar, Antoni Ribas. High antitumor activity of the ERK inhibitor SCH722984 against BRAF-mutant, NRAS-mutant and wild-type melanoma cell lines. [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 917. doi:10.1158/1538-7445.AM2013-917
Rat bite fever without the bite.
Authors: J N Fordham, E McKay-Ferguson, A Davies, T Blyth
Journal: Annals of the Rheumatic Diseases (1992)

The case is reported of a patient who developed an acute arthropathy, which was initially diagnosed as acute septic arthritis. The true diagnosis of rat bite fever due to Streptobacillus moniliformis was delayed because of difficulty in growing the organism, which has fastidious growth requirements. The patient had no history of rat bite, which is the usual form of transmission of this disease.
"FREE BEDS FOR MEDICAL TEACHING"
Authors: S. S. Goldwater
Journal: JAMA (1928)

<h3>To the Editor:</h3> —In the editorial entitled "Free Beds for Medical Teaching" (The Journal, Dec. 24, 1927) there are inaccuracies of a kind that one does not expect to encounter in the editorial pages ofThe Journal of the American Medical Association. You say that "the increasing cost of hospital service is causing the purely charitable bed to disappear in most instances except from institutions maintained by the city, county, state or national government." You say, again, that "in most of the hospitals maintained by religious organizations, definite minimum charges are made for space in large wards; the so-called free bed is practically nonexistent." And again, that "in most institutions the free beds are free when no patient able to pay is found to occupy them." It is true that in many nonmunicipal voluntary hospitals, supported by both religious and nonreligious bodies, the proportion of free beds is less today
Colon Decompression Using an Anatomically Adapted, Large-Caliber Decompression Probe
Authors: C. Ell
Journal: Endoscopy (1996)

Intestinal pseudo-obstruction, paralytic (e.g. postoperative or drug-induced) hyperdistension of the large bowel and colonic stenosis often require endoscopic decompression. The decompression probes currently available have the disadvantage of an insufficiently large diameter or inadequate adaptation to the given anatomic configuration of colon, or both. A new decompression probe system consisting of a guide wire, a 12-Fr polyethylene guide catheter, and a 24-Fr polyurethane decompression probe, is presented and two cases are described. The probe was tested in a pilot study in 16 patients. In all patients, implantation was successfully performed without complications. No undesired dislocation was observed. The introduction time varied between four and 16 minutes. Clinically successful decompression was achieved in 14 of the 16 patients.
Effects of inhibition of microtubule assembly on bone mineral release and enzyme release by human breast cancer cells.
Authors: G Eilon, G R Mundy
Journal: Journal of Clinical Investigation (1981)

When supernates from the established human breast cancer cell line MCF-7 were applied to fetal rat long bones that had been labeled with 45Ca and devitalized to remove endogenous bone cells, mineral was released from the bones. The release of bone mineral by MCF-7 supernates was associated with increased basal release of hydrolytic enzyme activity by the tumor cells. The basal release of lysosomal enzymes and collagenolytic activity by MCF-7 cells with approximately twice that of mouse 3T3 cells, which did not cause mineral release by the fetal rat bones. Release of hydrolytic enzymes and bone mineral-releasing activity was increased by colchicine and vinblastine, drugs that inhibit microtubule assembly, but not affected by lumicolchicine. Time-course experiments performed on MCF-7 cells with or without colchicine showed that release of cathepsin D and collagenolytic activity was associated more closely with release of bone mineral and degradation of bone matrix than was the release of N-acetylglucosaminidase. The release of previously incorporated [3H]proline from the bones exposed to MCF-7 cell cultures was more closely associated with release of collagenolytic activity by MCF-7 cells than with release of cathepsin D or N-acetylglucosaminidase. These data suggest that breast cancer-mediated bone resorption in vitro is positively correlated with release of hydrolytic enzymes by the tumor cells, and release of these enzymes is enhanced by disassembly of microtubules.
Transient Thyrotoxicosis Associated with Acute Hemorrhagic Infarction of Autonomously Functioning Thyroid Nodules
Authors: JOEL I. HAMBURGER
Journal: Annals of Internal Medicine (1979)

Two patients with nontoxic autonomously functioning thyroid nodules had transient hyperthyroidism after acute hemorrhagic infarction. Previously solid "hot" nodules were converted to cystic "cold" nodules. Aspiration confirmed the hemorrhagic nature of the process. There was marked regression in nodule size, marked reduction of nodular autonomous secretory activity (indicated by a change from a blunted to a normal response to thyrotropin-releasing hormone), and spontaneous recovery of function in the previously suppressed extranodular thyroid tissue. Confusion of this entity with a nontoxic autonomously functioning thyroid nodule that has progressed to the toxic stage may be avoided if the loss of nodular function is noted on imaging. The possibility of granulomatous thyroiditis may be excluded by blood aspiration.
464. Development of a Novel Gene Regulation System Downstream of Promoter
Authors: Hongzhe Duan, Chengwen Li, Richard Jude Samulski
Journal: Molecular Therapy (2005)

Current regulation systems for vector delivered transgene has focused primarily on controlling promoter activity. In this study, we assayed the ability to regulate expression of transgene cassettes after vector delivery downstream of promoter activity through use of alternative splicing. A unique human beta globin intron carrying a point mutation causing aberrant splicing was engineered into the open reading frame of vector expressing reporter or therapeutic transgene cassettes under constitutively expressing CBA promoter. After introduction into target cells, vector derived mRNAs are aberrantly spliced and no functional proteins are produced. Administration of target antisense oligonucleotides (AON) specific for alternative splice site restores wild type splicing and functional protein expression. Using this approach, we transfected luciferase reporter transgene cassettes carrying IVS2-654 intron plasmids into 293 cells. 24 hr post transfection cell lysates were obtained and luciferase assays preformed. We observed 6-8 folds increase in luciferase activity after AON treatment equivalent to levels obtained with wile type intron. This restoration of correct splicing and protein expression was not dependent on location of IVS2-654 intron. Regulated expression in vivo was tested using AAV vector carry regulated transgene cassette in mouse model. One week after portal vein injection of 1010 genomes, 25mg/kg AON was administered IP. We observed an 8-10 folds increase over control that persisted for over 1 month before returning to base-line level. Long-term study shows AON regulation 1yr. post vector administration. To further optimize this regulation system, we constructed a series of intron mutants that removed 250-400nt of 5' sequences as well as engineered point mutations that would strengthen use of alternative splice sites. Results of these efforts resulted in mutant intron cassettes that reduced background expression dramatically and resulted in 160-230 folds increase in protein expression after oligo treatment.
Two Cases of Alkaptonuria
Authors: A. W. McKenzie, J. A. Owen, J. H. R. Ramsay
Journal: BMJ (1957)

COMPLICATION OF DIGITALIS THERAPY BDITALJOIRL increased dosage of digitalis is required for uncontrolled auricular fibrillation, such treatment may be disastrous in the presence of the toxic arrhythmia.Even electrocardiographic analysis may be difficult.Well-defined P waves are helpful, and should be sought in all leads.Oesophageal leads may be necessary (Brown, 1936).Our patients were thought to have auricular fibrillation in the first instance.Cuttings from appropriate leads showing P waves were selected for the figures.An isoelectric interval between successive P waves helps to differentiate paroxysmal auricular tachycardia with auriculo-ventricular block from auricular flutter.Such electrocardiographic diagnoses as "impure flutter" and "impure fibrillation" should be regarded with suspicion, especially if the patient is receiving digitalis.It is doubtful if they have any fundamental meaning, and they may conceal the serious disturbance of auricular rhythm under review.In our cases the auricular rate varied between 195 and 230 a minute.Our cases were receiving digitalis when they developed paroxysmal auricular tachycardia with auriculo-ventricular block.The response to potassium treatment supports the view that digitalis was the causative agent (Cases 1, 2, and 3; Lown and Levine, 1955).An excessive dose of the drug may cause the arrhythmia, but it is important to realize that it may occur when the heart muscle is sensitized to digitalis by potassium loss (Lown, Salzberg, Enselberg, and Weston, 1951).Thus in intractable heart failure prolonged diuresis may render a therapeutic dose of digitalis a toxic dose, and thereby cause paroxysmal auricular tachycardia with auriculo-ventricular block.Prompt treatment is essential in paroxysmal auricular tachycardia with auriculo-ventricular block due'to digitalis toxicity.The drug, of course, must be stopped, and diuresis, paracentesis, and other measures aimed at diminishing the load
DIFFERENCE OF NEOINTIMAL FORMATION IN BIFURCATION LESION BETWEEN SIROLIMUS-ELUTING STENT AND PACLITAXEL-ELUTING STENT: OPTICAL COHERENCE TOMOGRAPHY STUDY
Authors: Takahiro Yoshimura, Masami Nishino, Naotaka Okamoto, Akihiro Tanaka, Atsushi Kikuchi, Takeshi Masaki, Naoki Mori, Daisuke Nakamura, Yasuharu Lee, Masayuki Taniike, Nobuhiko Makino, Hiroyasu Kato, Yasuyuki Egami, Ryu Shutta, Hisaki Morita, Jun Tanouchi, Yoshio Yamada
Journal: Journal of the American College of Cardiology (2011)
The Effect of Common Polymorphisms of the β<sub>2</sub>-Adrenergic Receptor on Agonist-Mediated Vascular Desensitization
Authors: Victor Dishy, Gbenga G. Sofowora, Hong-Guang Xie, Richard B. Kim, Daniel W. Byrne, C. Michael Stein, Alastair J.J. Wood
Journal: New England Journal of Medicine (2001)

With continuous exposure to β2-adrenergic agonists, vascular tissue becomes desensitized to agonist-mediated vasodilatation. We studied the effects of two common polymorphisms of the β2-adrenergic receptor, one at codon 16 and one at codon 27, on agonist-mediated vasodilatation and desensitization in the vascular bed.
Lead exposure in young children from dust and soil in the United Kingdom.
Authors: I Thornton, D J Davies, J M Watt, M J Quinn
Journal: Environmental Health Perspectives (1990)

A survey of metals in United Kingdom dusts and soils has confirmed widespread lead contamination with a geometric mean value for lead in surface (0-5 cm) garden soils of 266 micrograms/g and in housedusts of 561 micrograms/g (excluding old mining areas). A subsequent detailed survey of 97 householders in Birmingham with 2-year-old children showed dust lead loading in the home environment to be an important predictor of blood lead concentrations in young children, when both variables fell within the normal range for the U.K. The total estimated lead uptake by the young child was 36 micrograms/day of which 1 microgram was by inhalation and 35 micrograms by ingestion.
Regulator of G Protein Signaling 6 Mediates Doxorubicin-Induced ATM and p53 Activation by a Reactive Oxygen Species–Dependent Mechanism
Authors: Jie Huang, Jianqi Yang, Biswanath Maity, Daisuke Mayuzumi, Rory A. Fisher
Journal: Cancer Research (2011)

Abstract Doxorubicin (DXR), among the most widely used cancer chemotherapy agents, promotes cancer cell death via activation of ataxia telangiectasia mutated (ATM) and the resultant upregulation of tumor suppressor p53. The exact mechanism by which DXR activates ATM is not fully understood. Here, we discovered a novel role for regulator of G protein signaling 6 (RGS6) in mediating activation of ATM and p53 by DXR. RGS6 was robustly induced by DXR, and genetic loss of RGS6 dramatically impaired DXR-induced activation of ATM and p53, as well as its in vivo apoptotic actions in heart. The ability of RGS6 to promote p53 activation in response to DXR was independent of RGS6 interaction with G proteins but required ATM. RGS6 mediated activation of ATM and p53 by DXR via a reactive oxygen species (ROS)-dependent and DNA damage–independent mechanism. This mechanism represents the primary means by which DXR promotes activation of the ATM–p53 apoptosis pathway that underlies its cytotoxic activity. Our findings contradict the canonical theories that DXR activates ATM primarily by promoting DNA damage either directly or indirectly (via ROS) and that RGS6 function is mediated by its interactions with G proteins. These findings reveal a new mechanism for the chemotherapeutic actions of DXR and identify RGS6 as a novel target for cancer chemotherapy. Cancer Res; 71(20); 6310–9. ©2011 AACR.
On Volunteer Physicians in the Developing Nations
Authors: Charles Failmezger
Journal: JAMA (1979)

<h3>To the Editor.—</h3> I am writing this letter to encourage more American physicians to volunteer for shortterm medical service abroad. Longterm voluntary work is a specialty by itself and is not for most American physicians. On the other hand, those with a month or so to give can make an important contribution to world health when they are properly prepared. For 15 months, I was a volunteer physician in eight countries in Latin America. My experience taught me that the most important and durable goal for short-term physicians is to teach in medical and paramedical educational programs for the native personnel. Public health experts agree that the training of auxiliary medical personnel is the most practical means of expanding the medical care system in the developing nations. Before leaving the United States, however, the visiting physician must prepare for such a teaching program. Besides knowing the local diseases, one should
CLINICAL EXAMINATION OF THE URINE.A CRITICAL STUDY OF THE COMMONER METHODS.
Authors: RICHARD C. CABOT
Journal: JAMA (1905)

<h3>ACUTE DEGENERATION.</h3> In the 93 cases of this condition which I have studied, the diagnosis was correctly made in all but three. What I desire to point out here is: 1. That the urine may vary very greatly in composition in different cases, despite identical postmortem findings. 2. That in a few cases the diagnosis of something more serious than fever urine might have been made by any one accustomed to take his urinary analysis very seriously. I will take up this latter point first. Among the cases in which only acute degeneration was discovered postmortem, there were two called acute nephritis before death, and one called chronic nephritis. Besides these there was a case of puerperal eclampsia in which a nephritis of some type was assumed to be present, and in a case in which the patient died in convulsions suspected to be of uremie origin. It is a significant
Human CD4+ effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells
Authors: Gabriela González-Pérez, Norma C Segovia, Amaranta Rivas-Carvalho, Diana P Reyes, Honorio Torres-Aguilar, Sergio R Aguilar-Ruiz, Claudine Irles, Gloria Soldevila, Carmen Sánchez-Torres
Journal: Cellular and Molecular Immunology (2013)
Coprescribing and Codispensing of Cisapride and Contraindicated Drugs
Authors: Judith K. Jones
Journal: JAMA (2001)

Cisapride, an oral prokinetic drug indicated for the symptomatic treatment of nocturnal heartburn due to gastroesophageal reflux disease, was approved by the US Food and Drug Administration in July 1993. After reports of serious cardiac arrhythmias and deaths during administration of cisapride, most involving concomitant exposure to another drug, a series of label changes and warnings were issued in February 1995, October 1995, June 1998, and June 1999. Cisapride was removed from general distribution in July 2000.To determine the frequency of contraindicted coprescribing and codispensings, in which cisapride and a contraindicated drug were prescribed or dispensed to the same patient for overlapping periods, and the proportion of contraindicated coprescribing by the same physicians and codispensing by the same pharmacies.Retrospective study of prescription claims from a managed care organization database for all patients with cisapride prescriptions between July 1993 and December 1998.A total of 38 757 adult and pediatric patients who had a cisapride prescription immediately preceded by at least 60 days of insurance eligibility.Proportion of cisapride prescriptions or dispensing occurring during the same treatment period as a drug contraindicated at that time prescribed by the same physicians or dispensed by the same pharmacies.Of 131 485 cisapride prescriptions dispensed after the warnings began, 4414 (3.4%) overlapped with at least 1 drug contraindicated in the labeling at the time of the prescription. Of all overlapping prescription pairs, 2190 (50%) were by the same physicians, 3908 (89%) were by the same pharmacies, and 765 (17%) were dispensed on the same day.Prescriptions dispensed by the same pharmacies accounted for a far higher proportion of contraindicated medication pairs than prescriptions from the same physicians. The pharmacy may be an important and underutilized intervention point to prevent contraindicated drugs from being used together.
Cost and Price of Comparable Branded and Generic Pharmaceuticals
Authors: T. Donald Rucker
Journal: JAMA (1987)

<h3>To the Editor.—</h3> We share the Food and Drug Administration's concern<sup>1</sup>that the public needs more balanced information about generic drugs. In our opinion, the message of the study of costs of branded vs generic pharmaceuticals<sup>2</sup>was that, for just 11 drugs, consumers could save hundreds of millions of dollars by buying generic. We believe that the message of the article and editorial,<sup>3</sup>that buying generic is not always the best buy, fails to convey to the public the actual savings that generic drugs offer. We found Table 2 of the article confusing. It obscured the key data comparing costs paid by consumers for generic vs branded drugs. Even a reader familiar with both the generic and brand names for each product could easily fail to appreciate the consistent and rather considerable savings that generics offer. Instead, one gets lost going down the list, which also biases
Why I'm a reluctant rapid responder
Authors: Mina Fazel
Journal: BMJ (2004)

Irritation, inadequacy, and resignation were among my first feelings when I read the rapid responses on bmj.com to a paper I had published by the BMJ (2003;327: 134). And then the anger slowly crept in and stayed. I used to think rapid responses were a valuable and important way to maximise the learning opportunities inherent in publishing by enabling an exchange of ideas and knowledge. With two other doctors I had previously written a response to share our experiences of a rare medical disorder. I had also read the rapid responses to specific archived articles. But I felt completely different when reading the responses to my article.

Like anyone who has published research I had gone through the long and difficult tasks of writing a proposal, obtaining funding, getting ethical approval, collecting and analysing results, and then writing numerous drafts before sending the work to be considered for publication. After peer review, which included the opinion of …