tbuckley/cabot-search huggingface dataset:
Molecularly Targeted Oncology Therapeutics and Prolongation of the QT Interval
Authors: Elizabeth L. Strevel, Douglas J. Ing, Lillian L. Siu
Journal: Journal of Clinical Oncology (2007)

Investigation and utilization of molecularly targeted agents has induced a number of drug adverse effects that are not typically associated with conventional chemotherapy. QT interval prolongation, a cardiac toxicity that increases the risk of fatal arrhythmia, is associated with several novel oncology therapies. Classes of molecularly targeted agents with described QT effects include histone deacetylase inhibitors, multitargeted tyrosine kinase inhibitors, vascular disruption agents, farnesyl protein transferase inhibitors, Src/Abl kinase inhibitors, and protein kinase C inhibitors. Concurrently, guidelines for monitoring the QT-prolonging effects of drugs under development have become increasingly rigorous. Although these guidelines apply to anticancer agents, they were not specifically designed for the oncology patient population. This article will review the pathophysiology of QT prolongation, methods of preclinical QT assessment, and current guidelines for QT evaluation in early phase trials. Additionally, molecularly targeted agents with QT effects will be summarized, and mechanisms of addressing this toxicity in the context of oncology drug development will be explored.
Providing adequate and practical descriptions in surgical trials
Authors: N. Blencowe, N. Mills, P. Whiting, J. Blazeby
Journal: BMJ (2013)

Cook and colleagues highlight that descriptions of non-pharmacological interventions in randomised controlled trials are inadequate.1 Although reporting standards need to be improved, the level of information they suggest may not always be necessary.

Surgical interventions are complex, comprising many components that are delivered with multiple concomitant interventions (such as anaesthesia and postoperative care), so it may be impractical to control them all. Individual surgeons …
365 EPIDEMIOLOGY OF HEPATITIS E IN NORTHEASTERN CHINA, SOUTH KOREA AND JAPAN
Authors: S.R. Kim, M. Taniguchi, S. Mishiro, K. Takahashi, M.H. Shin, H. Yun, M.S. Park, Z.M. Li, M.K. Kim, J. Fang, Y. Hayashi
Journal: Journal of Hepatology (2009)
Letter: Doctors as managers.
Authors: H Binysh
Journal: BMJ (1975)

Miracle Cures SIR,-With reference to the opening para- graph of your leading article (5 July, p. 1), a much more likely diagnosis than Parkin- son's disease in the case of the woman com- memorated in St. Luke's Gospel would seem to be some affection of the spine such as ankylosing spondylitis or congenital kyphosis.In the authorized version it says (Chapter 13, v. 11) that she "was bowed together and could in no wise lift up herself," and, after her cure (v. 13),"immediately she was made straight."-Iam, etc., JOHN CAPWELL Aylsham, Norwich Hypertension-Which Arm? SIR,-The following problem was en- countered recently during blood-pressure screening men aged 50-54 in general practice.The blood pressure was measured in both arms in 33 patients and in 25 (76%) of them the diastolic pressure consistently differed between the two arms by at least 10 mm Hg.There was a corresponding variation in systolic pressure.The pressure was usually higher in the right arm than in the left, whichever was monitored first.This seems a generally unrecognized prob- lem both in defining mild hypertension and in monitoring treatment, unless all doctors concerned with the patient use the same arm for all readings.Five men out of 160 were clearly and consistently hypertensive, with diastolic pressures above 105 mm Hg.All were asymptomatic.A further 21 had one high reading.-Iam, etc.,
Tenofovir works as pre-exposure prophylaxis against HIV, two studies confirm
Authors: B. Roehr
Journal: BMJ (2011)

A monocyte function test (complement receptor enhancement) was undertaken on 45 patients with suspected bronchial carcinoma in whom this diagnosis was subsequently substantiated. In 38 (84%) complement receptor enhancement was below a range of values previously established for monocytes from 48 healthy control subjects and from 12 patients with non-malignant respiratory diseases. It was found that all 38 patients with reduced complement receptor enhancement had either local or widespread metastases, as determined by the chest radiograph and a variable combination of chest tomography, liver, bone and brain scanning, computed tomography, fibreoptic bronchoscopy, bone marrow aspiration, liver function tests, mediastinoscopy, and surgical assessment, where appropriate. By contrast, at the time of presentation there was no clear relationship between abnormal values in several conventional screening haematological or biochemical tests and the stage of the tumour. These results suggest that complement receptor enhancement might serve as a useful pointer to the extent of the disease, since low values were associated with extension within the chest and very low values were found with widespread metastases.
Coping Psychologically With Breast Cancer
Authors: Melvin J. Krant
Journal: JAMA (1981)

To the Editor.—  A recent article inThe Journalby Derogatis et al (242:1504, 1979) explored survival time and psychological coping mechanisms in patients with metastatic breast cancer. I would like to comment on the following two aspects of that work: the scientific validation system employed for the resulting conclusions and an evident bias system that influences interpretation of data. The growing concerns of holistic medicine and implications that psychological factors are inherent both as causal as well as life-adaptive factors in cancer require that extreme caution in methodology and interpretation be maintained.  The first question to be raised is whether the short-term survivors and the long-term survivors in the research experience are similar at the point of entry into the study. Although we are informed that the two groups are similar by statistical null hypothesis in regard to age and disease-free interval after their mastectomy, the mean age of
Translational regulation by p38 mitogen-activated protein kinase signaling during human cholangiocarcinoma growth
Authors: Yoko Yamagiwa, Carla Marienfeld, Laura Tadlock, Tushar Patel
Journal: Hepatology (2003)

The p38 mitogen-activated protein kinase (MAPK) signaling pathway is aberrantly expressed and maintains transformed cell growth in malignant human cholangiocytes. Because cell growth requires and is intimately related to protein synthesis, our aims were to assess the effect of p38 MAPK signaling on protein synthesis during growth of malignant human cholangiocytes. Inhibition of p38 MAPK activity during mitogenic stimulation decreased protein synthesis rates and tumor cell xenograft growth in nude mice. Altered protein synthesis resulted from decreased translational efficiency with impaired initiation of translation. Mitogenic stimulation resulted in phosphorylation of the eukaryotic initiation factor (eIF)-4E. Inhibition of p38 MAPK signaling or functional dysregulation of translation by small interfering double-stranded RNA (siRNA) to eIF-4E decreased anchorage-independent growth of malignant cholangiocytes. In conclusion, these studies identify a relationship between p38 MAPK activity and the regulation of protein synthesis during human cholangiocarcinoma growth. As protein synthesis is intimately linked to cell growth, dysregulation of translation initiation is a mechanism by which cellular p38 MAPK signaling participates in growth regulation of malignant cholangiocytes.
Cytophotometric measurements of nuclear DNA content in hepatocellular carcinomas
Authors: Sow-Hsong Kuo, Jin-Chuan Sheu, Ding-Shinn Chen, Juei-Low Sung, Chi-Chung Lin, Hey-Chi Hsu
Journal: Hepatology (1987)

The nuclear DNA contents of 54 hepatocellular carcinomas were measured on cytologic smears using a scanning microdensitometer at a wavelength of 550 nm. The cellular materials were aspirated under ultrasonographic guidance and stained with modified Feulgen method. The DNA modal values, which could be defined in 51 cases, ranged from 2.2 to 9.8 ploidy, with 46.3% (25/54) in hypertetraploidy. The hepatocellular carcinomas in patients with higher serum levels of α-fetoprotein contained more hyperploid cells. The DNA modal values did not correlate with the age, HBsAg status, tumor size and histological grading of hepatocellular carcinoma. The S-phase fraction values, which could be estimated on the DNA histograms in 43 cases (79.6%), ranged from 1 to 35 (mean ± S.D. = 10.6 ± 8.1). The S-phase fraction values were higher in high grade hepatocellular carcinomas (13.4 ± 8.5) than low grade hepatocellular carcinomas (6.1 ± 4.4), p < 0.01. The mean S-phase fraction values were also significantly higher in hepatocellular carcinomas with α-fetoprotein levels of more than 100 ng per ml than those of less than 100 ng per ml (12.9 ± 8.0 and 7.8 ± 5.6, respectively). The S-phase fraction values also did not correlate with the age, HBsAg status and tumor size.
The effect of pathophysiology on pharmacokinetics in the critically ill patient — Concepts appraised by the example of antimicrobial agents
Authors: Stijn I. Blot, Federico Pea, Jeffrey Lipman
Journal: Advanced Drug Delivery Reviews (2014)

Critically ill patients are at high risk for development of life-threatening infection leading to sepsis and multiple organ failure. Adequate antimicrobial therapy is pivotal for optimizing the chances of survival. However, efficient dosing is problematic because pathophysiological changes associated with critical illness impact on pharmacokinetics of mainly hydrophilic antimicrobials. Concentrations of hydrophilic antimicrobials may be increased because of decreased renal clearance due to acute kidney injury. Alternatively, antimicrobial concentrations may be decreased because of increased volume of distribution and augmented renal clearance provoked by systemic inflammatory response syndrome, capillary leak, decreased protein binding and administration of intravenous fluids and inotropes. Often multiple conditions that may influence pharmacokinetics are present at the same time thereby excessively complicating the prediction of adequate concentrations. In general, conditions leading to underdosing are predominant. Yet, since prediction of serum concentrations remains difficult, therapeutic drug monitoring for individual fine-tuning of antimicrobial therapy seems the way forward.
Progestin-Dependent Progression of Human Breast Tumor Xenografts: A Novel Model for Evaluating Antitumor Therapeutics
Authors: Yayun Liang, Cynthia Besch-Williford, Rolf A. Brekken, Salman M. Hyder
Journal: Cancer Research (2007)

Abstract Recent clinical trials indicate that synthetic progestins may stimulate progression of breast cancer in postmenopausal women, a result that is consistent with studies in chemically-induced breast cancer models in rodents. However, progestin-dependent progression of breast cancer tumor xenografts has not been shown. This study shows that xenografts obtained from BT-474 and T47-D human breast cancer cells without Matrigel in estrogen-supplemented nude mice begin to regress within days after tumor cell inoculation. However, their growth is resumed if animals are supplemented with progesterone. The antiprogestin RU-486 blocks progestin stimulation of growth, indicating involvement of progesterone receptors. Exposure of xenografts to medroxyprogesterone acetate, a synthetic progestin used in postmenopausal hormone replacement therapy and oral contraception, also stimulates growth of regressing xenograft tumors. Tumor progression is dependent on expression of vascular endothelial growth factor (VEGF); growth of progestin-dependent tumors is blocked by inhibiting synthesis of VEGF or VEGF activity using a monoclonal anti-VEGF antibody (2C3) or by treatment with PRIMA-1, a small-molecule compound that reactivates mutant p53 into a functional protein and blocks VEGF production. These results suggest a possible model system for screening potential therapeutic agents for their ability to prevent or inhibit progestin-dependent human breast tumors. Such a model could potentially be used to screen for safer antiprogestins, antiangiogenic agents, or for compounds that reactivate mutant p53 and prevent progestin-dependent progression of breast disease. [Cancer Res 2007;67(20):9929–36]
Sampling methods II
Authors: P. Sedgwick
Journal: BMJ (2011)

Researchers undertook a cross sectional study of the use of a coffee creamer as infant food in Laos. To ensure the study was nationally representative, they selected five districts across southern, central, and northern Laos. In total, 84 villages were randomly selected from the five districts. In each village an average of 14 households were randomly selected, and one adult from each household was invited to participate. It was reported that the coffee creamer was often used as a breast milk substitute in Laos, placing the health of infants at risk.1 Which one of the following best describes the sampling method used in the above study?
Abstract 4457: Omega-3 polyunsaturated fatty acids induce apoptosis cell death and inhibit LPS-induced invasion in PC3 cells
Authors: Kyoung-Sub Song, Soyeon Shin, Kaipeng Jing, Nayeong Kim, Soyeon Jeong, Jong-Seok Kim, Jun-Young Heo, Ji-Hoon Park, Kang-Sik Seo, Hyun-Joo Kwon, Jing X. Kang, Jong-Il Park, Seung-kiel Park, Gi-Ryang Kweon, Wan-Hee Yoon, Byung-Doo Hwang, Kyu Lim
Journal: Cancer Research (2010)

Abstract Dietary fat as a potential risk factor for cancer has been the focus of many epidemiologic and basic researchers, but the findings have been inconclusive. Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. In this study, we have investigated anticancer action of ω3-PUFAs and effect of ω3-PUFAs on LPS-mediated TLR4 signaling in prostate cancer. DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) treatment resulted in a dose-dependent reduction of cell viability with apoptosis of PC3 cells as confirmed by TUNEL assay. In contrast, AA (arachidonic acid), a ω6-PUFA, exhibited no significant effect. Moreover, invasiveness of PC3 cells was inhibited in a dose-dependent manner by treatment of DHA, while AA showed no significant effect. In zymography, MMP-2 activity was inhibited by DHA treatment and MMP-9 and MMP-2 promoter activities were also inhibited. DHA inhibited Cox-2 and VEGF promoter activities and NF-kB reporter activity was also decreased. The expression of TLR4 was confirmed by RT-PCR in PC3 cells and DHA dramatically inhibited the LPS-induced invasion of PC3 cells. In in vivo experiments, when mouse prostate cancer cells (RM1) were injected into the tail vein of Fat1 mice (Fat1 transgenic mice express a Caenorhabditis elegans ω3-desaturase converting ω6- to ω3-PUFAs endogenously.) and WT (wild type mice), lung metastasis was significantly inhibited in Fat1 transgenic mice compared to WT mice. In conclusion, the present study suggests that ω3-PUFAs may inhibit prostate cancer cell growth, and invasion through decrease of MMPs, Cox-2, VEGF and NF-kB reporter activities. Moreover LPS-mediated invasiveness was inhibited by DHA. These findings provide important preclinical evidence and molecular insight for utilization of ω-3 PUFAs for the chemoprevention and treatment of human prostate cancer. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Infection Signaling Network Research Center (R13-2007-020-01000-0) at Chungnam National University]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4457.
Lumbar Supports for Prevention of Low Back Pain in the Workplace
Authors: Timothy R. Dillingham
Journal: JAMA (1998)

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
Addition of n-3 fatty acids to a 4-hour lipid infusion does not affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus
Authors: Ingrid L. Mostad, Kristian S. Bjerve, Samar Basu, Pauline Sutton, Keith N. Frayn, Valdemar Grill
Journal: Metabolism (2009)
TCTAP A-209 Inferior Mesenteric Artery Preservation with Bare Stent in Endovascular Bilateral Iliac Aneurysm Repair Using a Bifurcated Stent Graft with Bilateral Internal Iliac Artery Coil Embolization
Authors: Kimihiro Igari, Toshifumi Kudo, masahiro Nakamura, Masato Nishizawa, Hidetoshi Uchiyama, Shinya Koizumi, Takahiro Toyofuku, Yoshinori Inoue
Journal: Journal of the American College of Cardiology (2014)
Medical students can cause blood pressure to rise, report says
Authors: Roger Dobson
Journal: BMJ (2004)

A new study has shown that the presence of a medical student can increase blood pressure when measured in general practice. The researchers found that blood pressure was significantly higher in consultations where measurements were taken in the presence of a medical student or trainee than in consultations where no student was present.

“If confirmed, our findings imply that doctors should be cautious to initiate or adjust antihypertensive drug treatment when blood pressure readings are obtained in the presence of a trainee,” say the researchers in their report ( Journal of Human Hypertension 2004;18:769-73).

In the study the researchers, from Ghent University, Belgium, recruited nearly 300 patients with …
Lithium Carbonate, Hypothyroidism, and Serum Creatine Phosphokinase Level
Authors: Vasantha Nair
Journal: JAMA (1980)

To the Editor.—  The article Lithium Carbonate-Induced Hypothyroidism, by James W. Jefferson, MD (242:271, 1979), showed that the need for a high index of suspicion for hypothyroidism in psychiatric patients receiving lithium carbonate is indeed evident. A similar instance of hypothyroidism mimicking drug effect came to our attention recently.  Report of a Case.—  A 43-year-old man with a diagnosis of schizophrenia was seen on referral from our psychiatric service. He had been receiving lithium carbonate, 900 mg daily, for the preceding six months. Thyroid function studies before therapy showed normal results. A routine autoanalyzer chemistry profile showed a creatine phosphokinase (CPK) level of 3,250 units/L (normal, less than 325 units/L). Abnormal physical examination findings were limited to mild dryness of the skin and prolongation of the relaxation time of the Achilles tendon reflex. The triiodothyronine (T3) resin uptake and thyroxine (T4) and thyroid-stimulating hormone (TSH) levels confirmed the diagnosis of
Re: Firas Abdollah, Giorgio Gandaglia, Nazareno Suardi, et al. More Extensive Pelvic Lymph Node Dissection Improves Survival in Patients with Node-positive Prostate Cancer. Eur Urol 2015;67:212–9
Authors: Jovo Bogdanović, Vuk Sekulić
Journal: European Urology (2015)
Gallium Scintigraphy in Hemodialysis Access Graft Infection
Authors: B. CHANDRAMOULY, H. CAO, S. COCHAVI
Journal: Clinical Nuclear Medicine (1993)

The authors report two cases of hemodialysis access-graft infection, diagnosed on Ga-67 citrate scintigraphy. The identification of graft infection is crucial in these patients because of serious complications, including septic emboli, endocarditis, and meningitis. The graft site should be included on gallium scintigraphy in hemodialysis patients with bacterial sepsis.
The impact of pegylated interferon and ribavirin combination treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients
Authors: Hee Jae Jung, Young Seok Kim, Sang Gyune Kim, Yun Nah Lee, Soung Won Jeong, Jae Young Jang, Sae Hwan Lee, Hong Soo Kim, Boo Sung Kim
Journal: Clinical and Molecular Hepatology (2014)

Lipid profile and insulin resistance (IR) are associated with hepatitis C virus (HCV) and may predict the chronic hepatitis C (CHC) treatment response. The aim of this study was to determine the association between CHC treatment response and lipid profile and IR change during treatment.In total, 203 CHC patients were reviewed retrospectively between January 2005 and December 2011 at Soon Chun Hyang University Hospital. The lipid profile, homeostasis model for assessment (HOMA) of IR (HOMA-IR), and HOMA of β cells (HOMA-β) were evaluated before interferon plus ribavirin therapy (BTx), at the end of treatment (DTx), and 24 weeks after the end of treatment (ATx).A sustained virologic response (SVR) was achieved by 81% of all patients (49/60), 60% (n=36) of whom possessed genotype 1, with the remainder being non-genotype-1 (40%, n=24). Apart from age, which was significantly higher in the non-SVR group (SVR, 48.0 ± 11.2 years, mean ± SD; non-SVR, 56.6 ± 9.9 years; P<0.01), there were no significant differences in the baseline characteristics between the SVR and non-SVR groups. In the SVR group, low density lipoprotein-cholesterol (LDL-C) had significantly changed at DTx and ATx compared to BTx. In addition, HOMA-IR and HOMA-β were significantly changed at DTx in the SVR group. Among those with a high baseline insulin resistance (HOMA-IR >2.5), HOMA-IR was significantly changed at DTx in the SVR group.LDL-C appears to be associated with HCV treatment in SVR patients. Furthermore, eradication of HCV may improve whole-body IR and insulin hypersecretion, as well as high baseline insulin resistance (HOMA-IR >2.5).