tbuckley/cabot-search huggingface dataset:
Phase II study of three hour, weekly infusion of trabectedin (ET-743) in men with metastatic, androgen-independent prostate carcinoma (AIPC)
Authors: M. D. Michaelson, T. Gilligan, W. Oh, P. Kantoff, M.-E. Taplin, M. A. Izquierdo, L. Flores, M. R. Smith
Journal: Journal of Clinical Oncology (2005)

4517 Background: Trabectedin (T) is a novel, marine-derived cytotoxic agent that binds to the minor groove of DNA and induces apoptosis and cell cycle arrest. T has been studied in phase I and II clinical trials in a variety of malignancies, and has clinical activity in soft tissue sarcoma, breast and ovarian carcinoma. Preclinical studies have demonstrated that low concentrations of T promote cell death in prostate cancer cell lines. Methods: We are conducting a phase II clinical trial to determine the efficacy and safety of T in men with AIPC. Men are treated with a weekly, three-hour infusion of T, at 0.580 mg/m2 for 3 out of 4 weeks. Inclusion criteria include adenocarcinoma of the prostate; androgen-independent disease by PSA criteria according to the PSA Working Group with testosterone<50 ng/ml; radiographic evidence of metastatic disease; and adequate hepatic function. Target accrual is 33 subjects. Results: A Simon’s two-stage design has been used, and based on the number of responses observed in the initial cohort, the trial has proceeded to the second stage. Twenty men have been enrolled to date, including 8 previously treated with docetaxel-based chemotherapy. Of those evaluable for response, there have been 3 men with a confirmed PSA response. One man with symptomatic, docetaxel-refractory AIPC has manifested an 86% decrease in PSA and rapid resolution of symptoms. Two other men have had PSA declines of 58.5% (first-line) and 79% (second-line following docetaxel/estramustine). Grade 3 adverse events related to study drug have been: elevated GGT (1 pt), thrombocytopenia (1 pt), fatigue (1 pt), and hyponatremia (1 pt). No grade 4 adverse events have been reported. Conclusions: Accrual should be completed in the next few months, and updated results will be presented. Preliminary results suggest that T is well tolerated and may have clinical activity in AIPC, including docetaxel-refractory AIPC. Additional studies including combination trials are warranted in this patient population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PharmaMar SA
Final results of PX-171–003-A0, part 1 of an open-label, single-arm, phase II study of carfilzomib (CFZ) in patients (pts) with relapsed and refractory multiple myeloma (MM)
Authors: S. Jagannath, R. Vij, K. Stewart, G. Somlo, A. Jakubowiak, S. Trudel, R. Schwartz, D. Siegel, L. Kunkel
Journal: Journal of Clinical Oncology (2009)

8504 Background: CFZ is a novel proteasome inhibitor of the epoxyketone class that exhibits a high level of proteasome selectivityand demonstrates antitumor activity in bortezomib (BTZ)-resistant MM pts in phase I studies. Methods: PX-171–003-A0 was an open-label, multicenter study that enrolled MM pts who relapsed from &gt;2 prior therapies, failed BTZ and at least 1 immunomodulatory agent [thalidomide (THAL) or lenalidomide (LEN)], and were refractory to last treatment [progressing on or within 60 d of last therapy or &lt;25% response to last therapy]. Pts received CFZ 20 mg/m 2 IV d 1, 2, 8, 9, 15 and 16 every 28 d for up to 12 cycles (C). Clinical benefit response (CBR) was defined as MR or better. Results: 46 pts were enrolled, including 78% with progression on or within 60 d of last therapy and 22% with no response to last therapy. 39 pts completed at least 1 C of CFZ, had measurable M-protein, and were evaluable for response. Median prior therapies was 5 (range 2–15). 100% of pts received prior BTZ, 91% prior THAL, 89% prior LEN, and 83% prior stem cell transplant (SCT) and all had failed combinations including anthracyclines (80%) and/or alkylating agents (94%). Pts received a median of 3 C (range 1–12); 13 pts completed ≥6 C. CBR was 26% (10/39 eval pts), including 5 pts achieving PR and 5 pts achieving MR. 5 BTZ-refractory pts achieved MR or PR. Median TTP was 6.2 mo, the median DOR for the MR + PR was 7.4 mo. 8/10 pts achieved response during C1. 16 additional pts achieved SD for at least 6 wks. The most common adverse events were fatigue, anemia, thrombocytopenia, nausea, upper respiratory infection, increased creatinine and diarrhea. Peripheral neuropathy occured in &lt; 10% of pts with 1 Gr 3 in a pt with pre-existing Gr 2. Conclusions: Single-agent CFZ achieved a TTP of &gt; 6 mo in relapsed and refractory MM pts who failed available therapies. 26% of patients had at least an MR and median duration of &gt;7 mo with this steroid- and anthracycline-sparing regimen. CFZ toxicities were manageable and importantly, exacerbation of pre-existing PN was rare. The study has been expanded to enroll an additional 250 pts in this unmet medical need population at an escalated dose, and treatment has been extended beyond a year. [Table: see text]
Fortnightly Review: Ambulatory blood pressure monitoring: a guide for general practitioners
Authors: N. Prasad, C. Isles
Journal: BMJ (1996)

<h3>Summary points</h3> Ambulatory blood pressure monitoring is an increasingly popular method of recording blood pressure It improves the precision and reproducibility of blood pressure measurement, eliminates observer errors and bias, and allows assessment of white coat hypertension and white coat responses It is indicated particularly in the evaluation of patients with borderline hypertension, resistant hypertension, or variable blood pressure None of the major trials of treatment in hypertension has been conducted using ambula- tory blood pressure recordings; because of this the prognostic value of such monitoring remains uncertain The optimal method of data analysis, the importance of day and night time readings and of white coat responses, cost effectiveness, and the fact that few marketed devices have been fully vali- dated also need addressing Despite these issues, ambulatory monitoring is already making an important contribution to the assessment and management of selected patients with high blood pressure
A Laboratory Guide to the Study of Parasitology.
Authors: William Brodbeck Herms
Journal: JAMA (1913)

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
Comorbidities, concominant medications, and clinical guidelines/algorithms in treating elderley patients with hormone receptor positive early breast cancer
Authors: A. Robinson
Journal: Journal of Clinical Oncology (2009)

e20680 Background: Guidelines and algorithms have been published for aspects of BC care such as adjuvant hormonal therapy, f/up testing, and mgmt of hormonal S/Es. This study examined how CPG's for BC address comorbidity in older patients, and applicability to frail elderly. Patterns on the use of adj hormonal therapy in patients &gt; 60, number of comorbidities, and concurrent medications was assessed at a single institution. Methods: Guidelines were obtained by searching the National Guideline Clearinghouse, as well as Pubmed. Guidelines on adjuvant anti-estrogen use for women with BC, follow-up, the use of bisphosphonates, and management of arthralgia in endocrine therapy treated patients were assessed. For the chart review, 290 consecutive patients over the age of sixty were reviewed for medication use, comorbid medical conditions, and anti-estrogen use. Results: The examined clinical guidelines and algorithms did not discuss the applicability of recommendations for older patients or those with multiple comorbidities. Fifty percent of patients in our sample had conditions where NSAID/COX2 use would be contraindicated. The median number of concurrent medicines at initial consult was 4. Patients &gt;70 were significantly more likely to not receive adjuvant hormonal therapy (21% vs. 10%, p=0.025). Conclusions: CPG's do not address the applicability of treatments in patients with multiple comorbidities or the frail elderly. Older patients may be significantly less likely to receive adjuvant hormonal therapies. A significant proportion of patients in our sample had risks for SAE's from the use of NSAIDs, which are commonly recommended to manage arthralgias associated with hormonal therapies. Assessing commonly used hormonal treatment and side-effect management drugs for potential interactions with concurrent medications is an important clinical step in personalized therapy. No significant financial relationships to disclose.
The Screening Handbook: A Practitioner's Guide
Authors: John Fry, Pauline Jeffree, Scott, Kenneth, Frcgp
Journal: Annals of Internal Medicine (1991)

1 Basics.- 2 Specifics.- 3 Training.- 4 Resources.- 5 Costs.- 6 Evaluation.- 7 White Paper and GP Contract: Implications.- 8 Future Prospects.- Appendix: National Groups and Associations.
Abstract 2126: CYP2C19 Genetic Variants and Clinical Outcomes With Clopidogrel: A Collaborative Meta-Analysis
Authors: Jessica L Mega, Tabassome Simon, Jeffrey L Anderson, Kevin Bliden, Jean-Phillippe Collet, Nicolas Danchin, Betti Giusti, Paul Gurbel, Benjamin D Horne, Adnan Kastrati, Gilles Montalescot, Franz-Josef Neumann, Lei Shen, Dirk Sibbing, P. Gabriel Steg, Dietmar Trenk, Stephen D Wiviott, Marc S Sabatine
Journal: Circulation (2009)

Introduction: Several studies have recently evaluated the relationship between CYP2C19 variants and risk of adverse cardiovascular (CV) events in the setting of clopidogrel treatment. However, risk...
Prognostic Significance and Determinants of the 6-Min Walk Test in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Caroline Zotter-Tufaro, Julia Mascherbauer, Franz Duca, Benedikt Koell, Stefan Aschauer, Andreas A. Kammerlander, Adelheid Panzenboeck, Roela Sadushi-Kolici, Christine Bangert, Daniela Laimer, Robin Ristl, Irene M. Lang, Diana Bonderman
Journal: JACC Heart Failure (2015)
The Design of Analgesic Clinical Trials
Authors: Mitchell Max, Russell K. Portenoy, Eugene M. Laska
Journal: Annals of Internal Medicine (1992)

In this text specialists in the area of analgesic trial design present a guide to the clinical evaluation of agents and methods for acute and chronic  control. The material in the book deals with topics such as chronic drug studies, tailoring designs to patients with specific diseases, probing neural mechanisms of pain, integrating recent advances in pharmacokinetics and statistics, and studying the effectiveness of efforts to improve clinicians' analgesic practice. For investigators studying the properties and clinical potential of analgesic compounds, the book reviews the regulatory requirements, describes the most efficient ways to screen for efficacy and toxicity, and explains how to plan a series of controlled trials, choosing from many standard clinical pain models. For clinicians seeking improved strategies for  relief, the book presents analgesic trials for specific types of  such as postoperative pain, neuropathic  syndromes, cancer pain, low back pain, osteoarthritis, sickle cell disease, sports injuries, orofacial pain, headache and dysmenorrhea. Also included are discussions of new methodologies in analgesic studies - such as multiple dose studies; comparing spinal, transdermal, and other novel routes to standard oral or systemic administration; patient-controlled analgesia paradigms; evaluation of analgesic prescribing practices; and advances in pharmacokinetics and biostatistics. Following many of the chapters are commentaries by experts in analgesic research that highlight unresolved issues and ongoing controversies.
Abstract 932: Temporal Relationship between QTc Prolongation and ST-segment Elevation in Early Transmural Myocardial Ischemia Measured by a Continuous 12-lead ECG Monitor
Authors: Marcin Kowalski, James Dobbs, Mohamad Sinno, David N Kenigsberg, Joel Xue, Subramaniam C Krishnan, Sanjaya Khanal
Journal: Circulation (2006)
V(a)3-21 gene utilizing chronic lymphocytic leukemias display restricted V lambda 2-14 gene usage and homologous CDR3s.
Authors: G Tobin, U Thunberg, A Johnson, I Eriksson, O Soderberg, K Karlsson, M Merup, G Enblad, Gunnar Juliusson, J Vilpo, C Sundstrom, G Roos, R Rosenquist
Journal: Blood (2002)
Silibinin’s effect on total EGFR, Erb-b2, and Erb-b3 expression in human colon cancer
Authors: F. Hogan, N. K. Krishnegowda, M. S. Kahlenberg
Journal: Journal of Clinical Oncology (2007)

14124 Purpose: Flavonoid, silibinin, has been shown to have strong chemotherapeutic activity in prostate, breast, bladder, skin, ovarian, and colon cancer. It has no documented LD50 and has been proven safe in multiple animal models and human trials. Cell cycle arrest and inhibition of protein levels of various cyclins are commonly reported in silibinin’s mechanism of action. We investigated silibinin’s activity on upstream cell-signaling targets, EGFR, Erb-b2, Erb-b3, Akt, Erk1/2, and mTOR, using three human colon cancer cells lines: Fet, Geo, HCT 116. Methods: The MTT cell-viability assay and FACS analysis were performed after silibinin treatment to substantiate its effect on proliferation and cell-cycle. Western blots for EGFR, Erb-b2, Erb-b3, Erk1/2, Akt, and mTOR were completed and quantified with densitometry. Standardization of protein loading was confirmed with cytoskeletal and house-keeping proteins, B-actin and GAPDH. Means were contrasted using analysis of variance with Dunnet’s correction for multiple testing. All statistical testing was two-sided with a significance level of 5%. Results: The MTT assay revealed a dose-dependent inhibitory effect. Treatment of FET and GEO at 75 micrograms/ml resulted in 50% inhibition of cell-viability (IC-50) at 72 hrs. An IC50 dose of 40 ug/ml was established for HCT116. FACS analysis demonstrated statistically significant cell-cycle arrest in all cell lines. G 2 -M phase arrests in Fet and Geo cell lines (p&lt;0.001) and a G1 arrest in HCT116 (p=0.005) were noted. Western blots showed decreased protein level expressions of total and phospho-EGFR, Erb-b2, Erb-b3, Akt, Erk1/2, and mTOR. Conclusions: Inhibition of protein expression levels of the Erb-b family of receptor tyrosine kinases plays a role in the mechanism of silibinin’s action. Strong inhibition of protein levels of total EGFR, Erb-b2, and Erb-b3 was noted as well as downstream decreases in total Erk1/2, Akt, and mTOR. Given silibinin’s inhibition of cancer proliferation and its safety profile, it is a promising compound requiring further mechanistic study, and applications in cancer therapy should be pursued given its effects on the Erb-b class of receptor tyrosine kinases and intermediary proteins, Erk1/2, Akt, and mTOR. No significant financial relationships to disclose.
Hunt promises more investment in general practice in return for seven day access
Authors: G. Iacobucci
Journal: BMJ (2015)

England’s health secretary has promised GPs “the biggest opportunity for new investment in a generation” if they commit to his government’s plans for seven day primary care services.

In a speech at a health centre in south London Jeremy Hunt promised to redress historical underinvestment in general practice as part of his “new deal” for the profession.1 But Hunt said the new investment would hinge on GPs embracing plans for seven day services that were currently being piloted across England.2

“New deals have two parties, so I want to be upfront: this is not about change I can deliver on my own,” he said. “If we are to have a new deal I will need your cooperation and support—both in improving the quality and continuity of care for vulnerable patients and delivering better access, seven days a week, for everyone.”

In a wide ranging speech Hunt vowed to tackle the current recruitment and retention crisis in general practice, reiterating his pre-election pledge to train 5000 new GPs and 5000 additional healthcare workers to work …
Die Wechseljahre der Frau.
Authors: Ernst Börner
Journal: JAMA (1928)

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
Abstract 16441: Influence of Diabetes Mellitus on Prognostic Utility of Cardiac Iodine-123-Metaiodobenzylguanidine in Diastolic Heart Failure Patients
Authors: Shigehiko Katoh, Tetsuro Shishido, Daisuke Kutsuzawa, Takanori Arimoto, Tetsu Watanabe, Isao Kubota
Journal: Circulation (2010)

Background: Iodine-123-metaiodobenzylguanidine (123I-MIBG) has been used to assess function of the cardiac sympathetic nervous system in patients with chronic heart failure. Recently, we and others...
Abstract 17412: Comparative Study of Factor Eight Inhibitor Bypass Activity and Recombinant Activated Factor VII in Refractory Post-Cardiopulmonary Bypass Bleeding
Authors: Vidya K Rao, Blake Bartlett, David Soran, Daryl Oakes, Charles Hill, Robert Lobato, Mark Klanjac, Christina Mora-Mangano, Pieter van der Starre
Journal: Circulation (2011)

Introduction. Profuse post-CPB bleeding occurs in up to 29% of cardiac surgical patients. Studies have shown rFVIIa to be a useful rescue procoagulant in bleeding refractory to conventional hemostatic measures. Recently, FEIBA, available for &lt;30% the cost of rFVIIa, has also been utilized in this setting. While efficacious, both compounds have been associated with thromboembolic events. This retrospective cohort study compares FEIBA and rFVIIa in treating refractory post-CPB bleeding. Methods. We reviewed records of all adult cardiac surgical patients who received FEIBA or rFVIIa from January 1, 2005 to September 30, 2010. Primary outcomes included total numbers of thromboembolic events in the first 30 post-operative days. Secondary outcomes included 30-day mortality, transfusion requirements prior to and after FEIBA or rFVIIa administration, and number of reoperations for excessive bleeding. Results. Of 2619 cases performed during the study period, 107 patients received FEIBA, and 61 received rFVIIa. There were no significant demographic differences between the cohorts, but patients in the rFVIIa group had significantly longer CPB times (305 v. 244 min) and were more frequently undergoing reoperations (56% v. 35%). There were no differences in the number of thrombembolic events, 30-day mortality, re-operations for bleeding, or overall transfusion requirements with the exception of platelets (FEIBA 1.7 v. rFVIIa 3.1). The most common thrombotic events in the FEIBA and rFVIIa cohorts were pulmonary embolism (5.6%) and stroke (6.6%), respectively. Discussion. This study contains the largest case series of FEIBA utilization in cardiac surgical patients to date, and suggests that FEIBA and rFVIIa may have similar efficacy and safety profiles when used for refractory post-CPB bleeding. FEIBA may represent an economically viable alternative to rFVIIa in this setting. Further studies are required to define the roles of these procoagulants in cardiac surgery.
Endoscopic Retrograde Pancreaticocholangiography (ERPC).
Authors: Hermann Anacker, Hans-Dieter Weiss, Bernhard Heinrich Kramann
Journal: Annals of Internal Medicine (1978)

1. Introduction.- Peroperative Pancreaticography.- Terminology.- 2. The History of Pancreaticography.- 2.1 Experiments on Pancreaticography by Means of a Balloon Catheter.- 2.2 Experiments on Pancreaticography by Direct Puncture of the Pancreatic Parenchyma.- 2.3 Experiments on Transvenous Pancreaticography.- 2.4 Development of the Endoscopic Retrograde Pancreaticocholangiography.- 3. Techniques.- 3.1 Equipment.- 3.1.1 Endoscopic Equipment.- 3.1.2 Catheters.- 3.1.3 Roentgenologic Equipment.- 3.1.4 Contrast Material.- 3.2 Preparation of the Patient.- 3.3 Technique of ERPC.- 3.3.1 Endoscopy in ERPC.- 3.3.2 Roentgenology in ERPC.- 3.4 Technical Difficulties in ERPC.- 4. Indications, Contraindications, and Complications.- 4.1 Indications for ERPC.- 4.2 Contraindications.- 4.3 Hazards, Complications, and Treatment.- 5. The Normal Retrograde Pancreaticogram (including anomalies and deformities).- 5.1 Site of the Papilla of Vater.- 5.2 The Anatomy of the Papilla of Vater.- 5.3 Main Duct and Side Branches of the Pancreas.- 5.4 Width of the Pancreatic Main Duct.- 5.5 Different Types and Variations of the Orifice.- 5.6 The Normal Emptying Process of the Pancreatic Duct.- 5.7 Transpapillary Pressure Measurement in the Pancreatic Duct and the Common Bile Duct.- 5.7.1 Method.- 5.7.2 Measuring Errors.- 5.7.3 Characteristic Pressure Tracings.- 5.7.4 Pressure Values in the Pancreatic Duct.- 5.7.5 Pressure Values in the Common Bile Duct.- 5.7.6 Pressure Values in the Duodenum.- 6. The ERPC Roentgenographic Pattern in Changes Due to Age.- 7. The ERPC in Lesions of the Pancreas and the Papilla Duodeni.- 7.1 Annular Pancreas.- 7.2 Chronic Pancreatitis, Chronic Relapsing Pancreatitis, Calculous Pancreatitis.- 7.3 Necrotizing Lesions and Pseudocysts.- 7.4 Papillary Stenosis and Papillary Spasm.- 7.5 Benign Tumors of the Pancreas.- 7.6 Carcinoma of the Pancreas.- 7.7 Papillary Carcinoma.- 7.8 Metastases of Tumors to the Pancreas.- 7.9 Posttraumatic Conditions of the Pancreas.- 7.10 Postoperative Conditions of the Pancreas.- 8. ERPC in Diseases of the Biliary Tract.- 8.1 Primary Sclerosing Cholangitis.- 8.2 Secondary Sclerosing Cholangitis and Postoperative Conditions of the Biliary Tract.- 8.3 Calculous Disease of the Bile Ducts and the Gallbladder.- 8.4 Carcinoma of the Bile Ducts and Carcinoma of the Liver.- 8.5 Stenosis of the Common Bile Duct Secondary to Diseases of Pancreas and Liver.- 9. Correlation of ERPC with Other Roentgenologic Examinations of the Pancreas.- 10. Conclusion.- 11. References.- 12. Subject Index.