tbuckley/cabot-search huggingface dataset:
Determining the preferred dose of the serotonin antagonist (5-HT3) palonosetron: Results of an individual patient data meta-analysis (MA) of 1,947 patients in all randomized double blinded (RDB) trials
Authors: M. Lesser, R. Gralla, B. Napolitano, H. Raftopoulos, M. Kline, E. Bria, D. R. Budman
Journal: Journal of Clinical Oncology (2009)

e20512 Background: Progress in antiemetic therapy has had a major impact on the administration of cancer chemotherapy (chemo). 5-HT3 agents are among the most used drugs in oncology and are considered the primary agents in guideline-recommended combination antiemetic regimens. Randomized trials have demonstrated advantages for palonosetron (palo) when compared with other 5-HT3 drugs in single agent trials (Ann Oncol 2003, Ann Oncol 2004) and recently in a combination trial with dexamethasone (Yoshizawa, ESMO 2008). With different doses of palo in use, we undertook this MA to determine if efficacy differs for palo doses of 0.75 mg or 0.25 mg. This has an impact on clinical dosing and on guideline recommendations as to whether there should be a preferred palo dose and a preferred 5-HT3 antiemetic. Methods: After a literature search and colleague inquiry, we identified 8 RDB trials; 4 in highly emetic (HEC) and 4 in moderately emetic (MEC) chemo that included treatment arms with 0.25 mg and 0.75 mg of palo; 6 IV and 2 PO trials. Primary endpoint: Complete Response (CR - no vomiting, no rescue) over days 1–5 after chemo. Secondary endpoints: Complete Control (CC - no vomiting, days 1–5); Acute emesis (day 1); Delayed emesis (days 2 - 5); by chemo (HEC / MEC); by other prognostic factors; by side-effects. Logistic regression, stratifying for protocol and including a treatment x protocol interaction term, was first used to test for heterogeneity (Het) of odds ratios (OR). In the absence of significant Het, the protocols were “pooled” in a protocol-stratified analysis. OR&gt;1 favors palo 0.75 mg. Results: Individual patient data were obtained for the 1947 subjects. Half were randomized to palo 0.25. No significant heterogeneity was found for CR or CC. For CR, the pooled OR = 1.00 (95% CI: 0.83–1.20); for CC, OR = 0.99 (95% CI: 0.83–1.89). Similar ORs for CR and CC were found for HEC and MEC, with no Het. Conclusions: We conclude that trials using 0.25 mg or 0.75 mg palonosetron doses yield similar efficacy for CR and CC so that reports with either dose can be used clinically or in guideline considerations. Findings are true for HEC and MEC regimens as well. [Table: see text]
Body images of one's self and of others: developmental and clinical significance
Authors: C D van der Velde
Journal: American Journal of Psychiatry (1985)

The author presents a new concept of the term "body image." He also introduces the term "extraneous body image," i.e., one's mental representation of others' appearance and behavior. The formation of one's own and extraneous body images and their role in the development of self-concept, concept of others, interpersonal relationships, and mind-body interactions, as well as their clinical implications, are discussed.
Pimping as a Practice in Medical Education—Reply
Authors: Cian P. McCarthy, John W. McEvoy
Journal: JAMA (2016)

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
Case 29-1964
Authors: Alan C. Aisenberg, Benjamin Castleman
Journal: New England Journal of Medicine (1964)

Presentation of CaseA seventy-one-year-old man was admitted to the hospital because of carcinoma of the mouth.Biopsy specimens taken from leukoplakic lesions of the mouth at intervals during the two years before admission had repeatedly shown squamouscell carcinoma. One year before entry a limited resection of the right lower gingival ridge was performed at another hospital. Six months later another biopsy specimen revealed recurrence. Four weeks before admission the patient began to experience pain in the chest; thereafter he became progressively obtunded. Two weeks later he entered another hospital, where marked leukocytosis was found.For many years he had . . .
Probable Future Trends in the Nutrition of Tissue Cultures&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Virginia J. Evans
Journal: JNCI Journal of the National Cancer Institute (1957)

Probable Future Trends in the Nutrition of Tissue Cultures Get access Virginia J. Evans Virginia J. Evans Tissue Culture Section, Laboratory of Biology, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 19, Issue 4, October 1957, Pages 539–553, https://doi.org/10.1093/jnci/19.4.539 Published: 01 October 1957 Article history Received: 28 May 1957 Published: 01 October 1957
Men’s involvement in family planning improves contraceptive use, study finds
Authors: Sanjeet Bagcchi
Journal: BMJ (2016)

Engaging men in family planning can substantially improve contraceptive practice and reduce sexual violence among married couples, a study published in PLoS One has found.1

The study assessed a gender equity and family planning counselling intervention, Counselling Husbands to Achieve Reproductive Health and Marital Equity (CHARM), in rural Maharashtra. The intervention included three sessions of counselling provided by male health workers to married men, both on their own (first and second session) and with their wives (third session).

Anita Raj, lead author of the study …
Liver Enzymes During Hepatic Carcinogenesis
Authors: Eberhard G. Trams, Joseph K. Inscoe, Robert A. Resnik
Journal: JNCI Journal of the National Cancer Institute (1961)

In rats fed a diet supplemented with N-2-fluorenylacetamide or N,N-dimethyl-p-phenylazoaniline, the activity of a number of microsomal and soluble liver enzymes was observed over a 24-week period. During this time the activity of the following enzymatic reactions was estimated periodically: glucuronyl transferase, the N-demethylation of morphine, the hydroxylation of acetanilide, tryptophan peroxidase, glutathione reductase, uridinediphosphateglucose dehydrogenase, and the reduction of the 4,5 double bond of ring A of cortisone. The activity of the enzymes, which N-demethylate morphine and hydroxylate acetanilide, decreased progressively toward the time when hepatoma formation occurs. In contrast, the glucuronyl transferase and the glutathione reductase showed significant increases in activity. N-2-fluorenylacetamide also induced a marked rise in the activity of the uridinediphosphateglucose dehydrogenase.
Reply from Authors re: Roderick C.N. van den Bergh, Declan G. Murphy, Henk G. van der Poel. Expectant Management for Prostate Cancer: Lessons from the Past, Challenges for the Future. Eur Urol 2016;70:767–8
Authors: Rebecka Arnsrud Godtman, Johan Stranne, Jonas Hugosson
Journal: European Urology (2016)
Blunted growth hormone response to peripheral infusion of human growth hormone-releasing factor in patients with panic disorder
Authors: M H Rapaport, S C Risch, J C Gillin, S Golshan, D S Janowsky
Journal: American Journal of Psychiatry (1989)

Patients with panic disorder (N = 11) and age- and sex-matched normal control subjects (N = 11) were challenged with human growth hormone-releasing factor (GH-RF) (1 microgram/kg i.v.) or placebo in random order. The control subjects had significantly increased plasma growth hormone (GH) levels after GH-RF infusion whereas panic disorder patients did not. At 15 and 30 minutes after GH-RF infusion, GH concentrations were significantly higher in the control subjects than in the patients. These findings with GH-RF extend findings from earlier reports that patients with panic disorder show blunted GH response to phobic stimulation and clonidine.
Systematic Analysis of AU-Rich Element Expression in Cancer Reveals Common Functional Clusters Regulated by Key RNA-Binding Proteins
Authors: Edward Hitti, Tala Bakheet, Norah Al-Souhibani, Walid Moghrabi, Suhad Al-Yahya, Maha Al-Ghamdi, Maher Al-Saif, Mohamed M. Shoukri, András Lánczky, Renaud Grépin, Balázs Győrffy, Gilles Pagès, Khalid S.A. Khabar
Journal: Cancer Research (2016)

Defects in AU-rich elements (ARE)-mediated posttranscriptional control can lead to several abnormal processes that underlie carcinogenesis. Here, we performed a systematic analysis of ARE-mRNA expression across multiple cancer types. First, the ARE database (ARED) was intersected with The Cancer Genome Atlas databases and others. A large set of ARE-mRNAs was over-represented in cancer and, unlike non-ARE-mRNAs, correlated with the reversed balance in the expression of the RNA-binding proteins tristetraprolin (TTP, ZFP36) and HuR (ELAVL1). Serial statistical and functional enrichment clustering identified a cluster of 11 overexpressed ARE-mRNAs (CDC6, KIF11, PRC1, NEK2, NCAPG, CENPA, NUF2, KIF18A, CENPE, PBK, TOP2A) that negatively correlated with TTP/HuR mRNA ratios and was involved in the mitotic cell cycle. This cluster was upregulated in a number of solid cancers. Experimentally, we demonstrated that the ARE-mRNA cluster is upregulated in a number of tumor breast cell lines when compared with noninvasive and normal-like breast cancer cells. RNA-IP demonstrated the association of the ARE-mRNAs with TTP and HuR. Experimental modulation of TTP or HuR expression led to changes in the mitosis ARE-mRNAs. Posttranscriptional reporter assays confirmed the functionality of AREs. Moreover, TTP augmented mitotic cell-cycle arrest as demonstrated by flow cytometry and histone H3 phosphorylation. We found that poor breast cancer patient survival was significantly associated with low TTP/HuR mRNA ratios and correlated with high levels of the mitotic ARE-mRNA signature. These results significantly broaden the role of AREs and their binding proteins in cancer, and demonstrate that TTP induces an antimitotic pathway that is diminished in cancer. Cancer Res; 76(14); 4068-80. ©2016 AACR.
Cardiac monitoring and toxicity with adjuvant trastuzumab in breast cancer: Data from clinical practice
Authors: R. Dienstmann, S. Viola, M. Chueke, M. Takemoto, N. Teich
Journal: Journal of Clinical Oncology (2008)

17551 Background: Adjuvant trastuzumab, recommended for HER2-positive early stage breast cancer, is associated with asymptomatic drop in left ventricular ejection fraction (LVEF) in 10–15% of patients and symptomatic congestive heart failure in 2–4%. There are limited data on cardiac toxicity with trastuzumab in clinical practice and there is no standard cardiac follow-up during adjuvant treatment. Phase III trials (NSABP B31/NCCTG N9831/ HERA) recommended echocardiograms at baseline, after anthracyclines and every 3 to 6 months afterwards. Methods: Retrospective evaluation of all patients with HER2-positive breast cancer treated in a private clinic with adjuvant trastuzumab since its approval in 2005. Timing and frequency of echocardiograms and cardiac adverse events were reviewed. Results: Forty-seven patients received adjuvant trastuzumab until December 2007. Thirty-three (70%) finished 1-year treatment and 14 are still on treatment (median 6 months, range 3–11). Median age: 51 years (range 31–82). No patient had uncontrolled hypertension or heart failure at baseline. Adjuvant chemotherapy was an anthracycline followed by taxanes in 41 patients (87.2%), anthracycline/ cyclophosphamide in 4 (8.5%) and docetaxel/ carboplatin in 2 (4.3%). Twenty-one patients (44.7%) have not received appropriate cardiac monitoring (considering published phase III trials). Seven patients (14.9%) had to discontinue trastuzumab (6 cases of asymptomatic LVEF drop and 1 symptomatic arrhythmia). Three patients resumed trastuzumab after 1-month interval. Four patients (8.5%) required permanent discontinuation of trastuzumab (3/7/11/11 months): 3 for a significant drop in LVEF (≤ 50%) and 1 due to arrhythmia). All these patients recovered from cardiac dysfunction and LVEF returned to baseline/ normal levels after treatment interruption (1 still on medication). Conclusions: Despite the absence of standard guidelines, our results show inadequate cardiac monitoring during adjuvant trastuzumab in a private clinic. Cardiotoxicity was observed as often as in clinical trials. Severity was mild and reversible in all patients. Continued and appropriate cardiac follow-up of these women is of critical importance. No significant financial relationships to disclose.
Potential Oncogenic Properties of High Polymers in Mice
Authors: William L. Kydd, Leo M. Sreebny
Journal: JNCI Journal of the National Cancer Institute (1960)

This experiment was designed to determine the oncogenic potential of a polymerized epoxy resin and an autopolymerizing methylmethacrylate. Two hundred, 6-week-old Harlan stock albino Swiss mice were used. One of the following 4 resins was subcutaneously implanted into the lateral abdominal wall of 50 animals: (1) epoxy resin (Epon 828 diethylenetriamine), (2) autopolymerizing methylmethacrylate (Caulk, NuWeld, Batch #8666), embedded 1 hour after processing, (3) heat-cured methylmethacrylate (Luxene), and (4) cellophane (5½ H. S. Visking sausage casing). The animals were observed daily until the incisions had healed, and then weekly for the presence of subcutaneous tumors. Under the conditions of this experiment no tumors were produced with any of the agents tested.
Inverse trends of Campylobacter and Salmonella in Swiss surveillance data, 1988–2013
Authors: Claudia Schmutz, Daniel Mäusezahl, Marianne Jost, Andreas Baumgartner, Mirjam Mäusezahl-Feuz
Journal: Eurosurveillance (2016)

Clinical isolates of Campylobacter spp. and Salmonella spp. are notifiable in Switzerland. In 1995, Campylobacter replaced Salmonella as the most frequently reported food-borne pathogen. We analysed notification data (1988-2013) for these two bacterial, gastrointestinal pathogens of public health importance in Switzerland. Notification rates were calculated using data for the average resident population. Between 1988 and 2013, notified campylobacteriosis cases doubled from 3,127 to 7,499, while Salmonella case notifications decreased, from 4,291 to 1,267. Case notifications for both pathogens peaked during summer months. Campylobacter infections showed a distinct winter peak, particularly in the 2011/12, 2012/13 and 2013/14 winter seasons. Campylobacter case notifications showed more frequent infection in males than females in all but 20-24 year-olds. Among reported cases, patients' average age increased for campylobacteriosis but not for salmonellosis. The inverse trends observed in case notifications for the two pathogens indicate an increase in campylobacteriosis cases. It appears unlikely that changes in patients' health-seeking or physicians' testing behaviour would affect Campylobacter and Salmonella case notifications differently. The implementation of legal microbiological criteria for foodstuff was likely an effective means of controlling human salmonellosis. Such criteria should be decreed for Campylobacter, creating incentives for producers to lower Campylobacter prevalence in poultry.
Abstract B34: Quantitative systems pharmacology and immunotherapy: accelerating lead generation and optimization of a PD-1 x TIM-3 biotherapeutic in immuno-oncology
Authors: Joshua F. Apgar, Jamie Wong, Ryan Phennicie, Mike Briskin, John M. Burke
Journal: Cancer Research (2016)

Abstract The goal of this collaboration was to provide early quantitative decision making guidance for the project team by developing and interrogating a quantitative systems pharmacology (QSP) model of the co-modulation inhibitory receptors PD-1 and TIM-3 in immuno-oncology. The QSP model was to: (1) provide predictions of the best-in-class profile for a PD-1 and TIM-3 dual antagonist biologic(s), (2) accelerate project timelines, (3) provide biological insights, and (4) reduce experimental costs. The QSP model was based on first principles as a system of elementary mass-action, mechanistic PKPD, ordinary differential equations. The model parameters and reactions were based on biophysics, and are interpretable. The model reactions include protein synthesis and elimination, ligand-receptor and drug-target formation and turnover, and drug administration and first order clearance. There were four versions of the model: PD-1 monospecific, TIM-3 monospecific, PD-1 x TIM-3 bispecific and fixed dose combination (FDC) targeting PD-1 and TIM-3. The monospecific models were then benchmarked against published data such that model parameter values were set to known values and unknown parameters were estimated. Once benchmarked, the FDC and bispecific models were analyzed by systematically investigating how tuning the model parameters (e.g., affinity, avidity, dose, half-life, target expression, etc.) impacted target inhibition, and to simulate patient variability. The model was in good agreement with published clinical data from nivolumab and pembrolizumab, and data from RMT3-23 in the TIM-3 driven mouse model. QSP model analysis predicted: (1) there would be diminishing returns on very tight binding biologics due to Target Mediated Drug Disposition (TMDD) that offsets potency, and (2) there is no advantage between FDC, 2-2 bispecific, and 2-1 bispecific formats, which are predicted to be roughly equivalent. As a result of these analyses, there was a significant reduction in the number of experiments, and acceleration of project timelines by (1) eliminating rounds of affinity maturation, as drug leads were in predicted optimal drug parameter ranges, and (2) eliminating the need to construct and evaluate bi-specific constructs and proceed with FDCs. Citation Format: Joshua F. Apgar, Jamie Wong, Ryan Phennicie, Mike Briskin, John M. Burke. Quantitative systems pharmacology and immunotherapy: accelerating lead generation and optimization of a PD-1 x TIM-3 biotherapeutic in immuno-oncology. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B34.
Decreased cerebral response to inhibitory neurotransmission in alcoholics
Authors: N D Volkow, G J Wang, R Hitzemann, J S Fowler, A P Wolf, N Pappas, A Biegon, S L Dewey
Journal: American Journal of Psychiatry (1993)

Changes in gamma-aminobutyric acid (GABA)-benzodiazepine receptor function have been implicated in alcohol tolerance, withdrawal, and dependence. The purpose of this study was to investigate whether recently detoxified alcoholic subjects had abnormalities in brain GABA-benzodiazepine receptor function.The effect of 30 micrograms/kg of lorazepam on regional brain glucose metabolism was studied in 12 normal subjects and 10 alcoholic subjects with the use of positron emission tomography and [18F]fluorodeoxyglucose.Lorazepam decreased whole brain glucose metabolism in both the normal subjects (13% change) and the alcoholic subjects (10% change), and the response was correlated with the concentration of lorazepam in plasma. Whereas the normal and alcoholic subjects showed similar responses to lorazepam in occipital and cerebellar metabolism, the alcoholic subjects showed significantly less of a response than the comparison subjects in the thalamus, basal ganglia, and orbitofrontal cortex. The rate of response in the orbitofrontal cortex was significantly correlated with cerebellar metabolism at baseline.The alcoholic subjects had a blunted response to lorazepam that was specific to certain brain regions. The association between cerebellar metabolism and response to lorazepam suggests that the cerebellum may contribute to the decreased sensitivity to lorazepam which was seen in the alcoholic subjects.
Aortic Centers of Excellence
Authors: Edward D. Gifford, Christian de Virgilio
Journal: JAMA Surgery (2016)

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 Surgery 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 Surgery journal