tbuckley/cabot-search huggingface dataset:
Exposure to Indoor Background Radiation and Urinary Concentrations of 8-Hydroxydeoxyguanosine, a Marker of Oxidative DNA Damage
Authors: Alessandra Sperati, Damiano D. Abeni, Christer Tagesson, Francesco Forastiere, Maria Miceli, Olav Axelson
Journal: Environmental Health Perspectives (1999)

We investigated whether exposure to indoor [gamma]-radiation and radon might be associated with enough free radical formation to increase urinary concentrations of 8-hydroxydeoxyguanosine (8-OHdG), a sensitive marker of DNA damage, due to a hydroxyl radical attack at the C8 of guanine. Indoor radon and [gamma]-radiation levels were measured in 32 dwellings for 6 months by solid-state nuclear track detectors and thermoluminescent dosimeters, respectively. Urine samples for 8-OHdG determinations were obtained from 63 healthy adult subjects living in the measured dwellings. An overall tendency toward increasing levels of 8-OHdG with increasing levels of radon and [gamma]-radiation was seen in the females, presumably due to their estimated longer occupancy in the dwellings measured. Different models were considered for females, with the steepest slopes obtained for [gamma]-radiation with a coefficient of 0.500 (log nmol/l of 8-OHdG for each unit increase of [gamma]-radiation on a log scale) (p<0.01), and increasing to 0.632 (p = 0.035), but with larger variance, when radon was included in the model. In conclusion, there seems to be an effect of indoor radioactivity on the urinary excretion of 8-OHdG for females, who are estimated to have a higher occupancy in the dwellings measured than for males, for whom occupational and other agents may also influence 8-OHdG excretion. ree radicals; [gamma]-radiation; radon.
ASYLUMS UNDER POLITICAL CONTROL.
Journal: JAMA (1902)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effects of Quinidine on Repolarization in Canine Epicardium, Midmyocardium, and Endocardium
Authors: Eugene A. Sosunov, Evgeny P. Anyukhovsky, Michael R. Rosen
Journal: Circulation (1997)

Background The antiarrhythmic action of quinidine is associated with a slowing of conduction and prolongation of repolarization. The latter effect has no consistent correlation with quinidine actions on action potential duration (APD) in isolated tissue experiments. To enhance our understanding of the mechanisms of quinidine action, we studied its effect on APD in canine epicardial, midmyocardial, and endocardial tissues. Methods and Results Standard microelectrode techniques were used to study the effects of quinidine 2.5 to 20 μmol/L on APD in ventricular epicardial, endocardial, and transmural (M-cell) slabs at cycle lengths (CLs) from 300 to 4000 ms. Qualitatively different time courses of actions and concentration- and rate-dependent effects were seen in M cells compared with the others. In endocardium and epicardium, quinidine induced monotonic and concentration-dependent APD prolongation at all CLs. In contrast, the effects of quinidine in M cells varied from prolongation to shortening, depending on duration of superfusion, concentration, and CL. Experiments with E4031 and TTX suggested that in M cells, quinidine-induced APD lengthening was attributable to block of delayed rectifier potassium current and APD shortening was due to inhibition of TTX-sensitive steady-state sodium current. Conclusions In vitro, there is a significant difference of quinidine effects in M cells versus epicardial and endocardial cells that appears to reflect differences in the contributions of specific ion channels to the APD at the three sites. The differences may influence the actions of quinidine on repolarization of the heart in situ and determine both the proarrhythmic and antiarrhythmic actions of the drug.
Massachusetts Medical Society
Authors: John Figgis Jewett
Journal: New England Journal of Medicine (1956)

RALPH RICKER STRATTONRalph Ricker Stratton died on November 27, 1955. For over half a century he practiced his profession as a doctor who loved to get sick people well. He had a heart as well as a head and hands. He brought to many a bedside in home and hospital the charm of manner that comes from a blending of the art with the science of medical practice. He never spared himself. To him a summons to attend someone who was ill was a duty never to be shirked. He was a good doctor.Dr. Stratton belonged to the . . .
EXTH-34. G-QUADRUPLEX DNA DRIVES GENOMIC INSTABILITY AND REPRESENTS A TARGETABLE MOLECULAR ABNORMALITY IN ATRX-DEFICIENT MALIGNANT GLIOMA
Authors: Yuxiang Wang, Jie Yang, Carla Danussi, Gregory Riggins, Erik Sulman, Timothy Chan, Jason T Huse
Journal: Neuro-Oncology (2018)

Mutational inactivation of ATRX (a-thalassemia mental retardation X-linked) represents a defining molecular alteration in large subsets of malignant glioma. ATRX encodes a chromatin binding protein widely implicated in epigenetic regulation and remodeling. However, multiple studies have also associated its loss in cancer with replication stress, DNA damage, and copy number alterations (CNAs). The mechanisms by which ATRX deficiency drives this global genomic instability remain unclear. Here we report that ATRX inactivation in isogenic glioma model systems induces replication stress and DNA damage by promoting the formation of deleterious G-quadruplex (G4) secondary structure in DNA. Moreover, these effects are associated with the acquisition of disease-relevant CNAs over time. Prior work has linked G4s with genomic instability as well as CNAs in cancer. We then demonstrate, both in vitro and in vivo, that chemical G4 stabilization with CX-3543 (Quarfloxin) selectively enhances cell death in ATRX deficient isogenic cell lines as well as ATRX-mutant primary glioma stem cells derived from patients. Finally, we show that G4 stabilization synergizes with other DNA-damaging therapies, including ionizing radiation, in the ATRX-deficient context. Our findings clarify distinct mechanisms by which DNA secondary structure influences ATRX-deficient glioma pathogenesis and indicate that G4-stabilization may represent and attractive therapeutic strategy for the selective targeting of ATRX-mutant cancers. Opportunities for the development of radiosensitization approaches based on G4-stabilization are particularly intriguing, as ionizing radiation remains among the most effective non-surgical treatments for malignant glioma.
Abstract 3632: Enhanced efficacy of optimized phenethyl isothiocyanate and cisplatin co-encapsulated liposome nanoparticle for treatment of non-small cell lung cancer
Authors: Mengwei Sun, Yi Shi, Anthony Di Pasqua
Journal: Cancer Research (2019)

Abstract Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which is the leading cause of cancer-related death in the United States. Accounting for about 85% of all lung cancers, NSCLC is difficult to treat and its survival rates are low. After decades of basic and clinical research, the most effective treatments still involve the first-generation anticancer agent cisplatin (CDDP) in combination with other drugs. Naturally-occurring compound, phenethyl isothiocyanate (PEITC), can be used to sensitize NSCLC cells to CDDP. We have previously proved that co-encapsulation of PEITC and CDDP in liposomes enhances the cytoxicity toward NSCLC cells, compared to free PEITC or CDDP. In this study, liposomal-PEITC-CDDP is optimized and the release of PEITC and CDDP from the nanoparticle is characterized. In vitro studies show that liposomal-PEITC-CDDP has a higher cytotoxicity toward both A549 and H596 human NSCLC cell lines than toward WI-38 and BEAS-2B human normal lung cell lines. Therfore, we have prepared an efficacious therapy with a potential for fewer side-effects due to low off-target toxicity. Citation Format: Mengwei Sun, Yi Shi, Anthony Di Pasqua. Enhanced efficacy of optimized phenethyl isothiocyanate and cisplatin co-encapsulated liposome nanoparticle for treatment of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3632.
MedisGroups-Reply
Authors: Lisa I. Iezzoni
Journal: JAMA (1989)

<h3>In Reply. —</h3> The letter by Dr Karlin provides useful insight into the early development of the MedisGroups severity measure. In the small study by physician-consultants at Boston University to which he refers, we asked four internists who were unfamiliar with MedisGroups to list those clinical variables that they thought indicated severity of disease for patients with stroke, lung cancer, chronic obstructive pulmonary disease, acute myocardial infarction, congestive heart failure, gastrointestinal tract hemorrhage, and diabetes mellitus.<sup>1</sup>We then compared these lists with the key clinical findings (KCFs) contained in an earlier version of MedisGroups than the version reported in our article (a version containing almost 550 KCFs rather than the current total of approximately 250). More than 80% of the variables identified by our consultants were included in the previous MedisGroups algorithm; many of the remaining 20% of variables either were often measured unreliably (such as pulsus paradoxus) or
Studies show possible oncogenic routes for HBV
Authors: K. Simmons
Journal: JAMA (1984)

In a carefully timed series of reports, a team of scientists from the University of California, San Francisco, School of Medicine (UCSF), has suggested a mechanism for dissemination of the hepatitis B virus (HBV) within the body, noting as well the implications for the role of HBV in causing cancer. Hubert E. Blum, MD, and co-workers of the Hepatitis Research Unit, Department of Laboratory Medicine, UCSF Liver Center, used the technique of in situ hybridization to analyze the liver tissue of three patients with chronic hepatitis B. This highly sensitive technique—in which radiolabeled, cloned DNA "probes" are allowed to hybridize with complementary viral DNA already present in the cell—allows the investigator to determine both the location and number of copies of viral DNA per cell. They first presented their work in the Oct 15, 1983 issue of<i>Lancet</i>, then in<i>Proceedings of the National Academy of Sciences</i>of November 1983,
Management of nausea and vomiting in the cancer patient
Authors: S. Frytak
Journal: JAMA (1981)

NAUSEA and vomiting are among the most common and distressing problems that the physician is called on to resolve in the cancer patient, particularly if the patient is undergoing chemotherapy or radiation therapy. If left unchecked, nausea and vomiting will result in depressed nutritional intake, serious metabolic derangements, deterioration of the patient's mental and physical condition, and possible rejection of potentially useful treatment of the malignant disease. Thus, control of these symptoms is essential for the patient's well-being and survival. <h3>Mechanisms of the Vomiting Reflex</h3> The coordination of the complex vomiting reflex is accomplished through the "vomiting center," located in the dorsolateral reticular formation of the medulla. Afferent input to this region comes from a number of sources. The viscera of the upper gastrointestinal (GI) tract send impulses through the vagii and sympathetic nerves. Radiation therapy, GI involvement with malignant disease, and some drugs may induce vomiting through this pathway.
THE RIGHT TO STRIKE
Journal: JAMA (1920)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Severe gastrointestinal distension during nitrous oxide and oxygen anesthesia
Authors: F. F. Foldes
Journal: JAMA (1965)

DURING the administration of nitrous oxide and oxygen mixture as an anesthetic the pressure and/or volume of gases contained in various body cavities or hollow organs may become markedly increased.<sup>1-3</sup>This increase in volume or pressure or both may interfere with various physiological mechanisms (eg, respiration and circulation in the presence of pneumothorax<sup>1</sup>) and may cause excessive increase in the intraventricular pressure during pneumoencephalography.<sup>2</sup> The following report describes the rapid development of alarming distension of the whole gastrointestinal tract during the administration of a nitrous oxide and oxygen mixture in a patient who had moderate abdominal distension preoperatively. <h3>Report of a Case</h3> A 34-year-old white married woman was admitted to the hospital for repair of a chronic ulcer of the lower part of the left leg. Twenty-seven months before admission the patient fell down a flight of stairs and sustained compound fractures of the distal lower left
Some advice on using condoms against STDs: what every man (and woman) should know
Authors: M. F. Goldsmith
Journal: JAMA (1987)

TO PREVENT sexual transmission of disease, it's important to use condoms, and use them properly. Robert Hatcher, MD, MPH, professor of gynecology and obstetrics at Emory University School of Medicine, Atlanta, says many people are trying them for the first time and don't know what they should do to make the best use of condoms. The following checklist is taken from Hatcher's book<i>Contraceptive Technology 1986-1987</i>, ed 13. New York, Irvington Publishers, 1987. It gives physicians a guide to follow in discussing condom use with male patients. It may also be used as a guide for discussing, with female patients, how they may initiate condom use to protect themselves and their partners from sexually transmitted diseases. <h3>Hatcher's "Condom Sense" Rules</h3> Use a condom every single time you have intercourse. There is no "safe" time with regard to transmitting disease. Put the condom on as soon as erection
Surgeons Hands
Authors: Alexander Gode
Journal: JAMA (1968)

<h3>To the Editor:—</h3> Yes, Dürer's "Hands of an Apostle" impress me profoundly. So does Dr. Mezger's reminder that a surgeon needs a head and a heart as well as a hand. I have been suspecting something of the sort. The suggestion that "surgeon" and "surgery" are not built from the same material as the parallel words in French, German, Italian, etc, is unnecessary, for the initial "ch" of "chirurg-" is a learned regrecization. It used to be an "s" (as in English).
Carpal Tunnel Syndrome
Authors: Mohammad Sidiq
Journal: JAMA (1972)

Carpal tunnel syndrome was the first manifestation of systemic lupus erythematosus (SLE) in two patients and was also present in one patient with a drug-induced lupus syndrome. All patients obtained relief with conventional treatment. The diagnosis of SLE was made because of a high index of suspicion for connective tissue disease in patients with carpal tunnel syndrome. As part of the examination for connective tissue disease, an antinuclear antibody test should be done in all patients with carpal tunnel syndrome of unclear cause.
Phase II, Open-Label Study of Brivanib as First-Line Therapy in Patients with Advanced Hepatocellular Carcinoma
Authors: Joong-Won Park, Richard S. Finn, Jun Suk Kim, Mark Karwal, Ruby K. Li, Fuad Ismail, Melanie Thomas, Rosemarie Harris, Christine Baudelet, Ian Walters, Jean-Luc Raoul
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Brivanib, a selective dual inhibitor of fibroblast growth factor and VEGF signaling, has demonstrated encouraging antitumor activity in preclinical and phase I studies. We performed a phase II open-label study of brivanib as first-line therapy in patients with unresectable, locally advanced, or metastatic hepatocellular carcinoma. Experimental Design: Brivanib was administered orally at a dose of 800 mg once daily. The primary objective was 6-month progression-free survival, progression-free survival rate; secondary objectives were tumor response rate, time to response, duration of response, median progression-free survival, median overall survival, disease control rate (complete response, partial response, or stable disease ≥ 42 days), and safety and tolerability. Results: Between March 2007 and May 2009, 55 patients were treated and were evaluable for response. Patients were assessed using modified World Health Organization (mWHO) criteria. According to mWHO criteria and as assessed by Independent Response Review Committee, the six-month progression-free survival rate (95% CI) was 18.2% (9.1%–30.9%). Median progression-free survival (95% CI) was 2.7 months (1.4–3.0). One patient achieved a complete response and three achieved a partial response. Twenty-two had stable disease. Median overall survival (95% CI) was 10 (6.8–15.2) months. Brivanib was generally well tolerated; the most common adverse events included fatigue, hypertension, and diarrhea. Conclusion: Brivanib as first-line therapy demonstrates promising antitumor activity and a manageable safety profile in patients with advanced, unresectable HCC. Clin Cancer Res; 17(7); 1973–83. ©2011 AACR.
A phase I/II trial of single-agent PTK 787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor, in patients with recurrent glioblastoma multiforme (GBM)
Authors: C. Conrad, H. Friedman, D. Reardon, J. Provenzale, E. Jackson, H. Serajuddin, D. Laurent, B. Chen, W. K. A. Yung
Journal: Journal of Clinical Oncology (2004)

1512 Background: VEGF-mediated signaling pathways may be critical to GBM neovascularization, and inhibition of VEGF pathways may be an important therapeutic target in GBM. PTK/ZK is a novel, oral angiogenesis inhibitor that potently inhibits all known vascular endothelial growth factor receptors (VEGFRs), and therefore blocks signaling by VEGF-A, -B, -C, and -D. Methods: PTK/ZK was administered once daily as oral monotherapy starting at 150 mg/day and escalating to 500, 1,000, 1,500, or 2,000 mg/day, with dose expansion at the 1,200- and 1,500-mg/day dose levels. The primary objective was to determine the safety and tolerability of continuous oral PTK/ZK in patients with recurrent GBM. A secondary endpoint was response to treatment (defined as decreases in tumor blood supply by dynamic contrast-enhanced [DCE] and dynamic susceptibility-change [DSC] MRI) and tumor response. Results: To date, 55 patients have been treated at these dose levels: 150 mg/day (n = 3); 500 mg/day (n = 6); 1,000 mg/day (n = 6); 1,200 mg/day (n = 20); 1,500 mg/day (n = 14); and 2,000 mg/day (n = 6). Median age was 54 years (range, 21–73 years), and median prior number of therapies was 4 (range, 1–12 therapies). Dose-limiting toxicities included liver enzyme elevation and deep-vein thrombosis (in 1/6 patients at 1,000 mg/day), insomnia or cerebral edema (in 2/14 patients at 1,500 mg/day), and fatigue or nausea/vomiting (in 2/6 patients at 2,000 mg/day). Among 47 evaluable patients, best responses were 2 (4%) partial responses, 31 (56%) stable disease, and 14 (25%) disease progression. Median duration of stable disease was 12.1 weeks (95% CI = 9.9, 15.1 weeks). DCE- and DSC-MRI scanning showed decreases in vascular permeability and cerebral blood volume, respectively, at days 2 and 30 of treatment; the decreases in both parameters at day 30 appeared dose dependent. Further assessment by blinded reviewers is ongoing. Conclusions: PTK/ZK monotherapy at 1,200 and 1,500 mg/day was well tolerated in patients with recurrent GBM, demonstrated changes in vascular permeability and blood volume, and stabilized disease in the majority of patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharmaceuticals Corp.; Schering AG Imclone; Novartis; Schering-Plough Imclone; Novartis; Regeneron; Schering-Plough; Schering AG Novartis
Platelet-Activating Factor Acetylhydrolase Prevents Myocardial Ischemia-Reperfusion Injury
Authors: Elizabeth N. Morgan, Edward M. Boyle, Wang Yun, John C. Kovacich, Timothy G. Canty, Emil Chi, Timothy H. Pohlman, Edward D. Verrier
Journal: Circulation (1999)

Background —Platelet-activating factor (PAF) is one of the most potent biological mediators of tissue injury. PAF acetylhydrolase (PAF-AH) is a recently isolated naturally occurring enzyme that hydrolyzes PAF and renders it inactive. We hypothesize that inhibition of PAF with PAF-AH will reduce myocardial ischemia-reperfusion (I/R) injury in vivo. Methods and Results —The coronary ligation model was used in New Zealand white rabbits. The large branch of the marginal coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. Fifteen minutes before reperfusion, animals were given either 2 mg/kg of vehicle or of PAF-AH. At the completion of 120 minutes of reperfusion, percentage of necrosis, degree of neutrophil infiltration, and measurements of regional contractility were assessed. Data are expressed as the mean±SEM and compared by Student’s t test or Mann-Whitney ANOVA. Both groups of animals showed an equivalent area at risk; however, 46.7±11% was necrotic in the animal treated with vehicle. In contrast, 20.9±7.0% was necrotic in the animals treated with PAF-AH ( P &lt;0.05). Systolic shortening and wall thickness were significantly greater in those animals treated with PAF-AH at 15, 30, 60, and 120 minutes of reperfusion ( P &lt;0.05). Quantification of neutrophil infiltration showed a 62% reduction in the PAF-AH treated animals compared with those treated with vehicle alone. Conclusions —PAF-AH is a potent cardioprotective agent in an in vivo model of I/R injury.