tbuckley/cabot-search huggingface dataset:
Introductory Remarks
Authors: Karl H. Beyer
Journal: JAMA (1964)

What happens after the "delight of discovery" of a new drug? Is the preclinical safety evaluation adequate? When is a clinical trial indicated? What safety factors must be considered? How are long-term clinical trials conducted? ANY DRUG, NEW OR OLD, miraculous or mediocre, will affect or appear to affect some patients adversely. Even bed rest has been called the most dangerous of therapeutic procedures. The safety of a drug can be assessed sensibly only in terms of what it is intended to do. Both modern therapeutics and the safety assessment of these remarkable new drugs have advanced tremendously in our generation of research and practice. Drug research is an exciting, exacting and demanding field wherein one constantly seeks to reach beyond the limits of present knowledge for achievement, knowing full well that an unknown, an unanticipated, or a previously unexamined aspect of a new and
Vestnik Otorinolaringologii, Moscow
Journal: JAMA (1966)

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
Reply:
Authors: Da-Qiang Li, Rakesh Kumar
Journal: Hepatology (2012)

We thank Dr. Vinciguerra for his interest in our article regarding synergistic inhibition of hepatocellular carcinoma (HCC) growth by cotargeting the enzymatic activities of histone deacetylases (HDACs) and poly(ADP-ribose) polymerases (PARPs) in HCC cell lines.1 The amplified in liver cancer 1 (ALC1, also known as CHD1L) oncogene, originally isolated in primary HCC, is frequently amplified and overexpressed in HCC, and plays an important role in HCC pathogenesis through promoting proliferation and inhibiting apoptosis.2 Subsequent studies demonstrate that ALC1 is specifically targeted to the sites of DNA damage through interaction with PARP1 and regulates chromatin remodeling during the process of DNA repair.3, 4 Consequently, knockdown of ALC1 results in increased cellular sensitivity to specific DNA damaging agents phleomycin and H2O2.3 Given that the HepG2 cells expressing high levels of ALC12 are sensitive to both PARP and HDAC inhibitors,1 there is increasing interest in seeing the expression status of ALC1 in SNU-398 and SNU-449 cell lines, with sensitive versus resistant phenotype to both enzymatic inhibitors, respectively. Interestingly, gene expression profiling analysis demonstrated no significant difference in ALC1 mRNA levels between both cell lines,1 suggesting that the observed distinct sensitivity of SNU-398 versus SNU-449 cells to PARP and HDAC inhibitors may be irrelevant to ALC1 expression levels, at least under the experimental conditions used in this study. Although HDAC inhibitor research in cancer therapeutics is still in its infancy, it has been demonstrated that the safety profile of HDAC inhibitors in phase I and II trials has been favorable, especially in comparison to traditional cytotoxic chemotherapy.5 Thus, a rational combination of selective and potent HDAC and PARP inhibitors may represent a promising avenue for inhibiting HCC growth, especially in molecularly defined HCC patient populations. Additional preclinical studies and clinical trials are definitely needed to validate these findings. Da-Qiang Li M.D.*, Rakesh Kumar Ph.D.*, * Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC.
SPERMOTOXIN AND ANTISPERMOTOXIN.
Journal: JAMA (1900)

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
JAPAN
Journal: JAMA (1960)

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
ACTH and Cortisone Therapy of Rheumatic Fever and Rheumatic Carditis
Authors: Benedict F. Massell
Journal: New England Journal of Medicine (1954)

Pericarditis. Data on the effect of cortisone or ACTH on this serious and obvious manifestation of rheumatic inflammation of the heart have been collected for 64 cases reported by 18 groups of investigators.4–6,11,18–21,24,27,29,30,35–38,40,43,44,46,49 The duration of the pericarditis after the beginning of therapy in these cases (usually indicated by the duration of a pericardial friction rub) is summarized in Table 1.In 6 fatal cases the signs of pericarditis continued until death. However, death occurred in 1 of these within twelve hours and in another within thirty-six hours of the beginning of treatment—long before there had been an opportunity for . . .
Portal hypertension and iron depletion in patients with genetic hemochromatosis*1, *2
Authors: A LUDOVICAFRACANZANI
Journal: Hepatology (1995)

Clinically, portal hypertension has been considered to be less common and less severe in patients with cirrhosis resulting from iron overload in homozygotes for genetic hemochromatosis than in patients with cirrhosis of other causes. To characterize the prevalence and progression of portal hypertension in genetic hemochromatosis (GH), 120 cirrhosis and iron-overloaded patients were compared with a control group of 120 patients with postnecrotic cirrhosis (PNC) who were matched for gender, age, Child's class, and alcohol abuse. Gastroesophageal endoscopy and abdominal ultrasonography were performed at diagnosis and repeated every 12 months and every 6 months, respectively, to evaluate the presence and severity of varices, the caliber of the portal vein and its collaterals, and splenic size. At diagnosis a similar frequency of varices was observed in patients with GH (25%) and in PNC (24%), as well as of portal vein abnormalities and spleen enlargement. During the follow-up period, all but two of the patients with GH were treated by phlebotomy and depleted of excess iron. After a mean of 6 ± 4.3 (SD) years of observations (range, 2 to 10 years), varices were improved or completely reversed in 26% of patients with cirrhosis and GH but in only 5% of those with PNC (P < .01). Bleeding from varices was observed in only one patient with GH but in five patients with PNC. Of 22 patients with GH in whom portal hypertension was unmodified or worsened, 16 had coexistent hepatic viral infection. The hazard risk for the development of de novo (i.e., a new occurrence) varices was 17 times higher in patients with PNC than in patients with GH (P < .001). The natural history of portal hypertension in patients with GH was substantially improved by phlebotomy therapy except in the presence of a coexistent hepatic viral infection. These results emphasize the need for intensive phlebotomy therapy even in patients diagnosed after the development of cirrhosis.
SUBMARINES AND SPACESHIPS
Journal: JAMA (1964)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
Home Testing Kits for HIV Apt to Get FDA Approval
Authors: Charles Marwic
Journal: JAMA (1995)

HOME TESTING KITS for spotting the AIDS agent are moving closer to approval. The Food and Drug Administration (FDA) has had a change of heart about approving these kits for detecting the presence of the human immunodeficiency virus (HIV). The agency's move reverses its earlier position, when it held that these kits could be used only under the supervision of a physician or other qualified health professional. The FDA now says that it would approve the kits for over-the-counter use as long as those with a positive test result are referred for counseling and postmarketing studies are put in place to assess the public health impact. This decision has once again fired up discussion of the value of home test kits for detecting HIV. Faced with the virtual certainty that the FDA will approve HIV test kits, the group Gays and Lesbians for Individual Liberty held a forum in Washington,
Relief of pain by oral medications. A controlled evaluation of analgesic combinations
Authors: C. G. Moertel
Journal: JAMA (1974)

A double-blind study of analgesic drug combinations was conducted, involving 100 patients with pain due to cancer. The combinations of 650 mg of aspirin plus either 65 mg of codeine, 9.76 mg of oxycodone, or 25 mg of pentazocine hydrochloride each produced significantly greater pain relief than aspirin alone. Side effects for a single dose of these effective combinations were essentially equal and clinically tolerable. The combinations of 650 mg of aspirin plus either 65 mg of caffeine, 32 mg of pentobarbital sodium, 25 mg of promazine hydrochloride, 75 mg of ethoheptazine citrate, or 100 mg of propoxyphene napsylate did not show significant advantage in analgesic effect over aspirin alone. (<i>JAMA</i>229:55-59, 1974)
Expression relationships among EGFR family members and c-Met in esophagogastric adenocarcinoma.
Authors: Ellie Chan, Ahmad Alkhasawneh, Lizette Vila Duckworth, Tania Zuluaga Toro, Xiaomin Lu, Steven J. Hughes, Thomas J. George
Journal: Journal of Clinical Oncology (2014)

75 Background: The incidence of esophagogastric adenocarcinoma is on the rise. The only targeted therapy that improves patient outcomes is the anti-HER2 antibody, trastuzumab; however, benefit is limited to cases with HER2 overexpression. Inhibition of EGFR in EGA is unsuccessful. cMet overexpression is a proposed resistance pathway for EGFR family inhibition. We sought to characterize the co-expression relationships among the EGFR family and cMet to identify potential dual therapeutic targets. Methods: This study included all sequential patients (pts) with adenocarcinoma of the esophagus and GEJ who underwent primary resection between 2001 to 2011 without neoadjuvant therapy or HER2 inhibition. Demographics, risk factors, tumor features, and outcome data were analyzed. Central blinded immunohistochemistry (IHC) was performed on FFPE tumor specimens with EGFR, HER2, HER3, HER4 and cMet expression scored as low/negative or high/positive expression. Descriptive statistics, Exact chi square test and Cox regression model were used for statistical analyses. Results: 48 pts (39 M/9 F) were eligible (median age 66yr; 37-83). Most (63%) were stage I (T1N0) and 93% had underlying Barrett’s esophagus. High expression of EGFR, HER2, HER3, HER4 and cMet were present in 70%, 43%, 77%, 38% and 56% of tumors respectively. HER3 and HER4 were commonly co-expressed (p=0.003) and moderately differentiated tumors had high expression of HER3 (p=0.01). Stage was the only variable that correlated significantly with survival (p=0.007). Conclusions: This study demonstrated that static baseline cMET expression levels are not associated with EGFR family expression profiles, although HER3/HER4 co-expression is common. No receptors demonstrated prognostic value. Further investigation into dynamic cMET expression changes related to active EGFR inhibition including prognostic and predictive value is warranted.
Extracorporeal renal parenchymal surgery with continuous perfusion
Authors: M. J. Sullivan
Journal: JAMA (1974)

MORE than ten years ago, inThe Journal, Hardy<sup>1</sup>reported the first successful renal autotransplantation in man. The indication for the operation was iatrogenic ureteral trauma. Subsequent reports have established the usefulness of this procedure in the treatment of other ureteral<sup>2-4</sup>and renovascular<sup>4</sup>lesions. A natural outgrowth of this procedure was the use of initial arterial washout and subsequent surface cooling<sup>5</sup>for vascular lesions requiring time-consuming reconstruction prior to reimplantation. Since continuous pulsatile perfusion with chilled, oxygenated, cryoprecipitated plasma has proved to be a more satisfactory means of renal preservation than surface cooling,<sup>6</sup>its use should afford greater protection to kidneys subjected to prolonged extracorporeal operative periods. Corman et al<sup>7</sup>first reported the use of extracorporeal renal parenchymal surgery with continuous pulsatile perfusion, which they unsuccessfully employed for bilateral renal carcinoma. The following is a case of successful extracorporeal renal perfusion and parenchymal surgery. <h3>Report of a Case</h3>
Exploration of the cGAS-STING pathway in prostate cancer.
Authors: Emma Reilly, Andrena McCavigan, Steven M. Walker, Nuala McCabe, Eileen Parkes, D. Paul Harkin, Richard D Kennedy, Laura A Knight
Journal: Journal of Clinical Oncology (2018)

5075 Background: Recent studies have demonstrated limited success of immune checkpoint therapies in unselected prostate cancer. We therefore assessed an immune based DNA Damage Repair Deficiency (DDRD) assay, that we previously reported represents activation of the cGAS STING pathway, in the TCGA prostate cancer dataset to investigate the presence of targetable immune biology. In order to assess if immune therapy could have a role in treating high risk disease, we applied a second assay (the prostate cancer metastatic signature-PCM) that predicts the risk of metastatic recurrence for early prostate cancer. Methods: 498 samples with RNA sequencing data were scored with the PCM and DDRD assays. Integrative analysis was performed on 488 samples with RNA sequencing, promoter site methylation, somatic mutation and somatic copy number variation. The subgroups were assessed for leukocyte infiltration and the expression of n = 6 immune checkpoint targets. The viability of reproducing those subgroups with RNA sequencing alone was tested in the TCGA dataset and an independent validation dataset of 321 resected primary prostate cancers. Cox proportional hazards regression analysis was performed for biochemical recurrence and metastatic events in both datasets. Results: Integrative analysis identified four patient subgroups characterised primarily by variances in copy number and genomic mutation. One of these subgroups ‘Metastatic-like DDRD’ had significantly higher PCM scores and DDRD immune scores compared to the other subgroups (p < 2E-12). This subgroup of patients showed elevated immune signalling (p < 2e-6) and greater genomic instability with amplification of 8q and a higher incidence of TP53 mutations. The ‘Metastatic-like DDRD’ subgroup was found to have a significant association with poor survival outcome in TCGA (multivariable: p < 0.008) and the independent dataset (multivariable: p < 0.01). Conclusions: We have identified and validated a poor prognostic subgroup, representing 10-20% of early prostate cancer patients that are at increased risk of developing metastatic disease and present with targetable immune biology. These patients may represent a viable target population for immune checkpoint and DNA damaging therapies in prostate cancer.
Carotid Endarterectomy
Authors: Frank A. Lederle
Journal: Annals of Internal Medicine (1990)

Letters and Corrections1 March 1990Carotid EndarterectomyFrank A. Lederle, MDFrank A. Lederle, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-112-5-383 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor:In the recent position paper developed for the American College of Physicians on carotid endarterectomy, Cebul and Whisnant (1) advocate surgery for patients with transient ischemic attacks and ipsilateral carotid stenosis. They support this position with results of the Joint Study of Extracranial Arterial Occlusion (2) after exclusion of the data on surgical complications. This exclusion invalidates the randomized design of the study, however. When the results of the Joint Study are properly viewed with the data on surgical complications included, 45 strokes and deaths occurred in 169 surgical patients (27%) and 38 in 147 medically treated...References1. . Indications for carotid endarterectomy. Ann Intern Med. 1989;111:675-7. LinkGoogle Scholar2. FieldsMaslenikovMeyersHassRemingtonMacDonald WVJWRM. Joint Study of Extracranial Arterial Occlusion. V. Progress report of prognosis following surgery or nonsurgical treatment for transient cerebral ischemic attacks and cervical carotid artery lesions. JAMA. 1970;211:1993-2003. CrossrefMedlineGoogle Scholar3. CebulWhisnant RJ. Carotid endarterectomy. Ann Intern Med. 1989;111:660-70. LinkGoogle Scholar4. ShawVenablesCartlidgeBatesDickinson DGNDP. Carotid endarterectomy in patients with transient cerebral ischaemia. J Neurol Sci. 1984;64:45-53. CrossrefMedlineGoogle Scholar1. CebulWhisnant RJ. Carotid endarterectomy. Ann Intern Med. 1989;111:660-70. LinkGoogle Scholar2. . Does carotid endarterectomy decrease stroke and death in patients with transient ischemic attacks? Ann Neurol. 1987;22:72-6. CrossrefMedlineGoogle Scholar3. . Indications for carotid endarterectomy. Ann Intern Med. 1989;111:675-7. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Frank A. Lederle, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPerioperative care of the vascular surgery patient 1 March 1990Volume 112, Issue 5Page: 383-384KeywordsCarotid endarterectomyPatient advocacyStenosisStrokeSurgeryTransient ischemic attacks ePublished: 1 December 2008 Issue Published: 1 March 1990 PDF downloadLoading ...
Stem Cell Transplants Found Superior
Authors: J. Stephenson
Journal: JAMA (2000)

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
THE THERAPY OF EXOPHTHALMIC GOITER
Journal: JAMA (1923)

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