tbuckley/cabot-search huggingface dataset:
Abstract 3519: Histone deacetylase inhibitors upregulates thymidine phosphorylase gene and protein expression and synergize with capecitabine in breast cancer cells
Authors: Elena Di Gennaro, Alessandra Di Cintio, Geny Piro, Maria I. Chianese, Francesca Bruzzese, Alfredo Budillon
Journal: Cancer Research (2011)

Abstract Capecitabine is a pro-drug which was designed to take advantage of the increased levels of thymidine phosphorylase (TP), a key enzyme for its conversion to 5-florouracil (5-FU), observed in tumours as opposed to normal tissues, potentially allowing for selective toxicity. Capecitabine is a valuable substitute for bolus or infusion 5-FU either as monotherapy or in combination with other cytotoxic drugs in the treatment of several tumor types including breast cancer. We have recently demonstrated for the first time, that the histone deacetylase-inhibitor (HDAC-I) vorinostat induces synergistic antitumour effects in combination with capecitabine by up-regulating, in vitro and in vivo, in colorectal cancer cells but not in ex vivo treated peripheral blood lymphocytes, the mRNA and protein expression of TP. We have also demonstrated that TP knockdown by a specific siRNA significantly impairs the synergistic apoptotic cell death induced by vorinostat/capecitabine combination. In this study we demonstrated a time and dose-dependent induction of TP mRNA and protein expression by several HDAC-Is in different breast cancer cell lines such MCF-7, SKBR3, MDA-MB-231and MDA-MB-468 cells. Interestingly, this effect was shared by pan-HDAC-Is such as panobinostat (LBH589), trichostatin A (TSA) or vorinostat and by class I HDAC-Is such as valproic acid (VPA) and entinostat (MS275), but not by the specific inhibitor of HDAC-6 tubacin, indicating that targeting class I HDACs is crucial for TP induction. Moreover, the mechanism of TP induction is dependent on a transcriptional effect since preliminary data showed that HDAC-Is did not interfere with TP protein stability. On these bases we investigated potential antitumor interaction between capecitabine and either vorinostat or panobinostat or VPA, demonstrating synergistic antiproliferative effects in all breast cancer cells independently of p53, ER or Her2 status. Overall, this study suggests that HDAC-Is, by upregulating TP expression, may improve the therapeutic index of capecitabine representing an innovative antitumour strategy for the treatment of breast cancer that warrants further clinical evaluation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3519. doi:10.1158/1538-7445.AM2011-3519
Proximal myopathy during beta-blockade.
Authors: J C Forfar, G J Brown, R E Cull
Journal: BMJ (1979)

Sites of abnormal 67Ga in 50 scans Abdomen 32Chest .12subphrenic .9mediastinum.7 renal .8lung fields.5 hepatic 2 Other.6 miscellaneous .13**Mostly operation sites-for example, uptake in scars-and intraperitoneal collections.operation sites-for example, uptake in scars-and intraperitoneal collections.Conditions underlying abnormal uptake included localised pus (32 cases), non-infective inflammation (six), tuberculosis (three), neoplasm (five), and transplant rejection (one); in three cases the cause was not clear.Of the 50 abnormal scans, 33 provided new, useful information resulting in an important change in diagnostic probability; 12 resulted in only a borderline change, confirming the presence of a highly probable lesion but excluding others; and five resulted in no change in diagnostic probability, which was already high.In none of the 17 patients with normal scans did follow-up disclose any focal cause for the PUO.Twelve normal scans resulted in an important change in diagnostic probability, and five resulted in a borderline change.All normal scans were of diagnostic value. CommentLocalisation of 67Ga in inflammatory lesions was first reported by Lavender et al.' Several authors have reported on its use in other conditions, but there have been few reports on the value of 6'Ga scanning in patients with PUO.I A recent review of PUO failed to mention this technique.:We suggest that 67Ga scanning is valuable in PUO even after blood and urine cultures and radiography.The high sensitivity of the technique is valuable in locating sites for further, possibly invasive diagnostic tests, though it is of low specificity.Conversely, a normal scan is valuable in excluding focal disease.Since this series was collected we have seen one presumed false-positive scan of a patient with focal uptake in the abdomen that resolved without treatment, and two false-negative scans of patients who were already taking applopriate antibiotics at the time of scanning.There are, of course, difficulties with 67Ga scanning: the isotope is expensive; available only on certain days; and-unless work load warrants a standing order, which may otherwise lead to wastagemust be ordered specially.Waiting for 72 hours for the result may be a problem, and contrary to the suggestion of Hopkins et a14 we do not find imaging six hours after injection to be helpful.Normal excretion of t'Ga in the bowel may also make interpretation difficult, especially after abdominal operations, when laxatives may be contraindicated.Despite these problems 67Ga-citrate scanning is a useful addition to non-invasive investigations of PUO.
Regionalization of High-Risk Surgery and Implications for Patient Travel Times
Authors: John D. Birkmeyer
Journal: JAMA (2003)

Given the strong volume-outcome relationships observed with many surgical procedures, restricting some procedures to hospitals exceeding a minimum volume standard is advocated. However, such regionalization policies might cause unreasonable travel burdens for surgical patients.To estimate how minimum volume standards for esophagectomy and pancreatic resection would affect how long patients must travel for these procedures.Simulated trial based on Medicare claims and US road network data. All US hospitals in the 48 continental states were in the study if their surgical procedures included esophagectomy and pancreatic resection. Data from Medicare patients (N = 15,796) undergoing these 2 procedures for cancer between 1994 and 1999 were used.Additional travel time for patients required to change to higher-volume centers as a result of alternative hospital volume standards (procedures per year).With low-volume standards (1/year for pancreatectomy; 2/year for esophagectomy), approximately 15% of patients would change to higher-volume centers, with negligible effect on their travel times. Most patients would need to travel less than 30 additional minutes (74% pancreatectomy; 76% esophagectomy). Many patients already lived closer to a higher-volume hospital (25% pancreatectomy; 26% esophagectomy). Conversely, with very high-volume standards (>16/year for pancreatectomy; >19/year for esophagectomy), approximately 80% of patients would change to higher-volume centers. More than 50% of these patients would increase their travel time by more than 60 minutes. Travel times would increase most for patients living in rural areas.Many patients travel past a higher-volume center to undergo surgery at a low-volume hospital. If not set too high, hospital volume standards could be implemented for selected operations without imposing unreasonable travel burdens on patients.
The Chicago Fire and the Chicago AMA Meeting
Authors: Donald F. Richardson
Journal: JAMA (1966)

<h3>To the Editor:—</h3> I am sure that the program of the 1966 AMA convention will have been "illuminating, sparkling, and at times heated" just as prophesied on your May 9 cover. On the other hand, I hope that it is not as confused as the artist must have been who painted the cover picture of "The Great Fire at Chicago." He shows the fire as burning toward the southwest; actually it started near 12th and Halsted streets, and burned northeast and north! In any event it was a whale of a fire, and I'm sure yours will have been a whale of a meeting.
Granulocytes from chronic myeloid leukemia (CML) patients show differential response to different chemoattractants
Authors: V. Radhika, S. Thennarasu, Nishighanda R. Naik, Ajay Kumar, S. H. Advani, A. N. Bhisey
Journal: American Journal of Hematology (1996)

Binding of chemoattractant to polymorphonuclear leukocytes (PMNL) triggers a series of events like polymerization of actin and tubulin, orientation of cells, chemotaxis, increase in fluid pinocytosis and phagocytosis, and stimulation of microbicidal pathways which includes lysosomal degranulation and generation of reactive oxygen species. Earlier studies from our laboratory have shown that stimulation of chemotaxis, fluid pinocytosis, and actin polymerization of CML PMNL in response to a synthetic chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMLP) is significantly lower than that in normal PMNL. It is not known whether this lower response of CML PMNL to fMLP is a global phenomenon involving different chemoattractant receptors or is restricted to the fMLP pathway. We have evaluated chemoattractant induced degranulation process in normal and CML PMNL to fMLP, platelet activating factor (PAF), leukotriene B4 (LTB4), and an analogue of fMLP viz formyl-methionine-1 aminocyclooctane 1 carboxylic acid-phenylalanine-O-methionine (FACC8) using release of lysozyme as a parameter. We find that after stimulation with fMLP and FACC8, the mean percent release of lysozyme was significantly lower in CML PMNL as compared to that in normal cells (P < 0.001). There was no significant difference between the two after stimulation with PAF and LTB4. The results indicate that the fMLP pathway is suppressed in CML granulocytes whereas PAF and LTB4 pathways appear unaltered in these cells. We therefore also studied the kinetics of peptide-receptor interaction with a labelled hexapeptide fNLPNTL which binds to the fMLP receptor. Our results show that the number of fMLP receptors/cell is significantly lower in CML PMNL (P < 0.05) than in normal PMNL, while their affinity constants and dissociation constants were comparable.
Alopecia Associated with Fluconazole Therapy
Authors: Lowell A. Goldsmith
Journal: Annals of Internal Medicine (1996)

Letters15 July 1996Alopecia Associated with Fluconazole TherapyLowell A. Goldsmith, MDLowell A. Goldsmith, MDUniversity of Rochester School of Medicine and Dentistry Rochester, NY 14642Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-2-199607150-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest the recent report on reversible alopecia related to fluconazole therapy [1]. Hair shaft and hair sheath structures were not described in the report. After systemic illness, a precipitation of the telogen (resting) phase of the hair cycle often causes hair loss. Alopecia also occurs after fasting, after pregnancy, with hypothyroidism, and with iron deficiency [2]. Telogen hairs can be easily recognized on a hair pull, and the diagnosis can be confirmed by scalp biopsy. Anagen effluvium follows chemotherapy or irradiation, both of which affect the rapidly proliferating cells of the hair matrix. Such ...References1. Pappas PG, Kauffman CA, Perfect J, Johnson PC, McKinsey DS, Bamberger DM, et al. Alopecia associated with fluconazole therapy. Ann Intern Med. 1995; 123:354-7. Google Scholar2. Fiedler VC, Hafeez A. In: Olsen EA, ed. Disorders of Hair Growth—Diagnosis and Treatment. New York: McGraw-Hill; 1994:241-55. Google Scholar3. Grossman KL, Kvedar JC. Anagen hair loss. In: Olsen EA, ed. Disorders of Hair Growth—Diagnosis and Treatment. New York: McGraw-Hill; 1994:223-39. Google Scholar4. Strauss JS, Rapini RP, Shalita AR, Konecky E, Pochi P, Comite H, et al. Isotretinoin therapy for acne: results of a multicenter dose-response study. J Am Acad Dermatol. 1984; 10:490-6. Google Scholar5. Van Wauwe J, Coene MC, Cools W, Goossens J, Lauwers W, Le Jeune L, et al. Liarozole fumarate inhibits the metabolism of 4-keto-all-transretinoic acid. Biochem Pharmacol. 1994; 47:737-41. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Rochester School of Medicine and Dentistry Rochester, NY 14642 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAdverse Effects Associated with Long-Term Administration of Azole Antifungal AgentsCutaneous effects associated with fluconazole in patients treated for coccidioidomycosisExamination of Fluconazole-Induced Alopecia in an Animal Model and Human CohortCurrent use of anti-infectives in dermatology 15 July 1996Volume 125, Issue 2Page: 153KeywordsChemotherapyHypothyroidismImidazoleIron deficiencyMetabolitesPregnancyRetinoic acidRetinoidsToxicityVitamin A Issue Published: 15 July 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Evaluation of Duct-Cell and Acinar-Cell Function and Endosonographic Abnormalities in Patients With Suspected Chronic Pancreatitis
Authors: Tyler Stevens, John A. Dumot, Gregory Zuccaro, John J. Vargo, Mansour A. Parsi, Rocio Lopez, H. Lester Kirchner, Edward Purich, Darwin L. Conwell
Journal: Clinical Gastroenterology and Hepatology (2008)
Primary Pulmonary Hypertension
Authors: A P Fishman, G G Pietra
Journal: Annual Review of Medicine (1980)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
A Case of Two Synchronous Primary Lung Tumors Demonstrated by FDG Positron Emission Tomography
Authors: J Antonio Obando, Jason M. Samii, Mona Yasrebi
Journal: Clinical Nuclear Medicine (2008)

The authors describe an F-18 FDG PET scan, which demonstrates 2 synchronous primary lung malignancies. An 81-year-old male with a history of prostate and bladder cancer presented with a left nodular opacity on a chest radiograph. Further workup including an evaluation with a PET scan revealed intense FDG uptake in a left lower lobe mass and moderate FDG uptake in a right middle lobe opacity. Subsequent pathology revealed adenocarcinoma of the right middle lobe and squamous cell carcinoma of the left lower lobe. The characterization and diagnosis of 2 synchronous primary tumors were suggested by PET.
Progress in the development of preventive and therapeutic vaccines for hepatitis C virus
Authors: Joseph Torresi, Doug Johnson, Heiner Wedemeyer
Journal: Journal of Hepatology (2011)

Hepatitis C virus (HCV) is a blood borne disease estimated to chronically infect 3% of the worlds' population causing significant morbidity and mortality. Current medical therapy is curative in approximately 50% of patients. While recent treatment advances of genotype 1 infection using directly acting antiviral agents (DAAs) are encouraging, there is still a need to develop vaccine strategies capable of preventing infection. Moreover, vaccines may also be used in future in combination with DAAs enabling interferon-free treatment regimens. Viral and host specific factors contribute to viral evasion and present important impediments to vaccine development. Both, innate and adaptive immune responses are of major importance for the control of HCV infection. However, HCV has evolved ways of evading the host's immune response in order to establish persistent infection. For example, HCV inhibits intracellular interferon signalling pathways, impairs the activation of dendritic cells, CD8(+) and CD4(+) T cell responses, induces a state of T-cell exhaustion and selects escape variants with mutations CD8(+) T cell epitopes. An effective vaccine will need to produce strong and broadly cross-reactive CD4(+), CD8(+) T cell and neutralising antibody (NAb) responses to be successful in preventing or clearing HCV. Vaccines in clinical trials now include recombinant proteins, synthetic peptides, virosome based vaccines, tarmogens, modified vaccinia Ankara based vaccines, and DNA based vaccines. Several preclinical vaccine strategies are also under development and include recombinant adenoviral vaccines, virus like particles, and synthetic peptide vaccines. This paper will review the vaccines strategies employed, their success to date and future directions of vaccine design.
Ian Pretyman Stevenson
Authors: Janice Hopkins Tanne
Journal: BMJ (2007)

Psychiatrist who researched reincarnation with scientific rigour



In a personal essay in the Journal of Scientific Exploration in 2006 Ian Stevenson wrote: “We all die of some affliction. What determines the nature of that affliction? I believe the search for the answer may lead us to think that the nature of our illnesses may derive at least in part from previous lives. The cases of children who claim to remember previous lives and who have related birthmarks and birth defects suggest this; some such children have related internal diseases. My own physical condition, defects of my bronchial tubes (from early childhood on) of which I have written separately, has given me a personal interest in this important question. Let no one think I know the answer. I am still seeking.”

Stevenson was born in Ottawa, Canada, in 1918. He died last month of a chronic lung infection. As a sickly child often bedridden with bronchitis, he was cared for by his devoted mother. He read widely in …
Impact of Implantable Cardioverter-Defibrillator Therapy on a Secondary Prevention Population—Reply
Authors: Ryan T. Borne, Paul D. Varosy, Frederick A. Masoudi
Journal: JAMA Internal Medicine (2013)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Use of Ambulatory Electrocardiographic (Holter) Monitoring
Authors: John P. DiMarco
Journal: Annals of Internal Medicine (1990)

Purpose: To evaluate the clinical efficacy of ambulatory electrocardiographic (ECG) monitoring and to develop guidelines for its use in clinical practice. Data Identification: Studies reported since January 1978 were identified both through computer searches using Index Medicus and extensive manual searching of bibliographies of identified articles. Study Selection: Only studies that fulfilled methodologic criteria designed to limit bias were reviewed. Data Extraction: Information describing population and study results was assessed in four major categories (variability, diagnosis, prognosis, and therapy guidance) for both arrhythmia monitoring and ST-segment analysis. Results of Data Analysis: The day-to-day variability of arrhythmia and myocardial ischemia detected by ambulatory ECG monitoring may be considerable in an individual patient. Caution must therefore be used in interpreting serial tests. Ambulatory ECG monitoring with diary correlation permits documentation of cardiac arrhythmias causing symptoms, but the diagnostic yield is low unless symptoms are frequent. Such monitoring can provide information about prognosis in patients after acute myocardial infarction. The amount of prognostic information obtained is modest and is outweighed by other measures. There is insufficient information to make conclusions about such monitoring and prognosis in other conditions. Serial ambulatory ECG monitoring may be used to assess the effect of an antiarrhythmic drug in patients with frequent and reproducible ventricular ectopy. The effect of arrhythmia suppression on survival is uncertain. Because of its low sensitivity and specificity, analysis of ST-segment changes during ambulatory ECG monitoring is inaccurate in establishing or excluding the presence of coronary disease. Although anti-ischemic interventions reduce the frequency and duration of ST-segment changes on monitoring, there are no data on the utility of using reduction or elimination of the changes as the endpoint of therapy. Conclusions: Ambulatory ECG monitoring can provide diagnostic, prognostic, and therapeutic information in many situations, but similar information often may be better obtained in other ways.
End stigmatizing language in tuberculosis research and practice
Authors: M. Frick, D. v. Delft, B. Kumar
Journal: BMJ (2015)

Terms that invoke metaphors of transgression and punishment cause harm, say Mike Frick , Dalene von Delft , and Blessina Kumar 

After years of relative quiet,1 advocacy in the global response to tuberculosis is growing louder and increasingly includes the voices of people who have been affected themselves.2 One priority identified by this growing movement is to stop the stigmatizing language still commonplace in research and practice. This is long overdue; indeed, stigma resulting from discriminatory terms may have discouraged the advocacy now calling for reformed discourse.3

In 2012 Zachariah and colleagues called for an end to stigmatizing language in tuberculosis programs, an appeal supported by the Stop TB Partnership.4 5 Unfortunately, three years later, the Stop TB Partnership’s guidance document on patient centered language remains in draft,6 and health professionals in many programs worldwide still use stigmatizing terms. These remain rife in journal articles, conference abstracts, and even some treatment guidelines, as well as in technical expert meetings.

It is no coincidence that the language used in tuberculosis—often called a disease of poverty—mirrors the stigmatizing language used to describe …
Contribution of lead in dust to children's blood lead.
Authors: M J Duggan
Journal: Environmental Health Perspectives (1983)

The importance of urban dust as a source of lead for young children is still disputed. Although blood-lead data from various population surveys usually show a peak concentration in early childhood, there is evidence that such a peak is small or absent altogether in children without much access to the general environment. An examination of those studies where groups of people in regions of low and high lead contamination have been compared shows that the child/adult blood-lead ratio is almost always enhanced in the more exposed groups. This implies a route of lead uptake which is important for children but less so for adults, and it is likely that this route is the dust-hand-mouth one. There are sufficient data to suggest a quantitative relationship between raised levels of blood lead and lead in dust. There is a strong case for a lead-in-dust standard but some will probably remain unpersuaded unless or until there are reliable data for blood lead and environmental lead involving matched groups of young people from urban and rural areas.