tbuckley/cabot-search huggingface dataset:
Toward Better ICU Use at the End of Life
Authors: Derek C. Angus, Robert D. Truog
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 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
Molecular monitoring of chronic phase chronic myeloid leukemia patients treated with 800 mg imatinib
Authors: M. Albitar, J. Cortes, F. Giles, W. Ma, H. Kantarjian, A. Salvado, I. Sams, S. Goldberg, B. Bayard Powell, J. Radich
Journal: Journal of Clinical Oncology (2005)

6554 Background: Imatinib mesylate (STI571; Gleevec) is very effective in the therapy of chronic phase chronic myeloid leukemia (CML). Early data suggests that the 800 mg of imatinib may be more effective than 400 mg. However, a little data is available on the role of molecular monitoring in patients receiving 800 mg of imatinib. Methods: We used quantitative reverse transcriptase-polymerase chain reaction (Q-PCR) for monitoring patients enrolled in a non-randomized open-label study of high dose imatinib mesylate in patients with newly diagnosed chronic phase CML. The ABL gene is used as an internal control and the results are reported as a ratio of fusion BCR-ABL/ABL. Results: Data from 56 patients at baseline, 32 pts. at 3 month, 18 pts. at 6 month, and 3 pts. at 9 months was analyzed. The median ratio of BCR-ABL/ABL in bone marrow (BM) was not significantly different from that in peripheral blood (PB). However, significant reduction in levels of BCR-ABL/ABL ratio was noted at 3 moths of therapy (P5 logs. Using a one-step real-time PCR assay, the current data reveals BCR-ABL-negativity in 34% of patients at 3 month, 56% at 6 month and 67% at 9 month. The levels of BCR-ABL transcript at 3 months correlated with Sokal score (R=0.69, P=0.03). Levels of BCR-ABL at all time points correlated with FISH results (R=0.57, P<0.0001). There was also excellent correlation between results obtained using two different laboratories (Quest Diagnostics and Fred Hutchinson Cancer Research Center) (R=0.64, P<0.0001). As an attempt to measure the disease in the entire body rather than in the limited number of cells in the collected sample, we used Q-PCR to measure BCR-ABL transcript in isolated plasma from these samples. BCR-ABL transcript levels from mRNA isolated from plasma and cells showed excellent correlation (R=0.80, P<0.0001). Plasma levels of BCR-ABL were not significantly different from those in cells at baseline, but were significantly higher than cellular levels at 3 months of therapy. Conclusions: This data suggests that Q-PCR provides a useful means for monitoring CML patients being treated with 800 mg imatinab and we believe that long follow-up will help in developing Q-PCR-based algorithm for therapeutic strategy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis
Blood Donor Ban Is Eliminated
Authors: Rebecca Voelker
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 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
Relationship between VHL mutation status, tumor VEGF expression and plasma VEGF measurement in sporadic renal cell carcinoma
Authors: P. Fergelot, N. Rioux-Leclercq, S. Zerrouki, K. Bensalah, J. Patard
Journal: Journal of Clinical Oncology (2006)

4602 Background: The relationship between VHL mutation status and prognosis in renal cell carcinoma (RCC) remains controversial. The aim of this study was to evaluate prospectively the association between VHL status, tumor VEGF expression, plasma VEGF levels and usual prognostic parameters in RCC. Methods: 70 patients with clear cell RCCs were included in this study. Genomic DNA was extracted using the QIAmp DNA mini kit (Qiagen) from frozen tumor samples. Four amplimers covering the whole coding sequence and exon/intron junctions of the VHL gene were synthetized by PCR followed by Big Dye sequencing (Applied Biosystems). Mutation bearing sequences were confirmed in a second round of PCR and sequencing reactions. Tumor VEGF expression was determined by immunohistochemistry and plasma VEGF was measured by enzyme-linked immunosorbent assay (Quantikine immunoassay, R&amp;D systems). Results were expressed in pg/ml. Qualitative and quantitative variables were compared by using Chi-square (Fischer exact test) and Student t tests, respectively. Results: A VHL mutation was found in 46 cases (65.7%). VHL mutations were localized in exon 1, 2 and 3 in 23, 16 and 7 cases respectively. Median tumor VEGF expression was 45% (5–100). Median plasma VEGF was 104 pg/ml (13–1430). A significant association was found between VHL mutation and N stage (p: 0.01), Fuhrman grade, symptoms at presentation (p: 0.02) or tumor size (p: 0.007). A VHL mutation was found in 83.5% of low grade (G1–2) and 80% of incidental tumors respectively. A trend towards more frequent VHL mutations was observed in T1 tumors (87% mutation rate, p: 0.07) and in good performance status patients. Interestingly, VEGF tumor expression and plasma VEGF levels were not significantly different among patients with tumors having or not mutated VHL (p: 0.7). Conclusion: VHL mutations are more frequent in small incidental low stage or low grade tumors. Although VHL inactivation was not specifically determined in this study, we failed to show any association between VHL mutational status and VEGF tumor or plasma expression suggesting that other pathways than the VHL/HIF axis are required for explaining the angiogenic phenotype of RCC. No significant financial relationships to disclose.
Phase II trial of docetaxel in patients with platinum-refractory advanced ovarian cancer.
Authors: P Francis, J Schneider, L Hann, C Balmaceda, R Barakat, M Phillips, T Hakes
Journal: Journal of Clinical Oncology (1994)

PURPOSE This phase II study was conducted to evaluate the efficacy and toxicity of docetaxel in the treatment of patients with platinum-refractory ovarian cancer. PATIENTS AND METHODS Twenty-five patients with platinum-refractory advanced ovarian cancer were treated. Twenty of the patients had failed to respond to platinum-based front-line chemotherapy and five had failed to respond to platinum-based therapy repeated at relapse. One patient had received prior pelvic radiation therapy. Patients were required to have bidimensionally measurable disease. Docetaxel was administered at a dose of 100 mg/m2 intravenously (i.v.) over 1 hour every 21 days. Twenty patients received no corticosteroid premedication and five received premedication with corticosteroids and antihistamines. RESULTS Eight of 23 assessable patients (35%) had a partial response (PR; 95% confidence interval, 16% to 57%). The median response duration was 5 months. Hospitalization for toxicity, predominantly neutropenic fever, occurred in 12 patients (48%) and 16% of courses. Anemia was common in the study population. Nonhematologic toxicities included alopecia, rash, fluid retention, diarrhea, peripheral neuropathy, and hypersensitivity reactions. CONCLUSION Docetaxel demonstrates significant activity in patients with platinum-refractory advanced ovarian cancer. Routine premedication is recommended. Further investigations of this agent in ovarian cancer, including combinations with other active agents, appear indicated.
Hormonally Induced Renal Neoplasia in the Male Syrian Hamster and the Inhibitory Effect of 2-Bromo-α-ergocryptine Methanesulfonate 2
Authors: J. M. Hamilton, A. Flaks, P. G. Saluja, S. Maguire
Journal: JNCI Journal of the National Cancer Institute (1975)

One group of male Syrian hamsters received diethylstilbestrol (DES) over a period of 9 months. All developed widespread and severe renal tumors. Another group of male Syrian hamsters was given DES plus 2-bromo-alpha-ergocryptine methanesulfonate (CB154) over the same period. These hamsters either did not develop renal tumors or had renal tumors that were minimal in severity. DES treatment induced hyperplastic and neoplastic changes in the intermediate lobe of the pituitary glands of treated animals, increased the number of prolactin-secreting cells, and decreased the number of somatotrophin-secreting cells. Adding CB154 significantly inhibited those changes in the pituitary gland. Histopathologic and ultrastructural examinations indicated that the renal tumors were carcinomas originating from proximal convoluted tubules.
Thymic Epithelial Tumor-Associated Cytopenia: A 10-Year Observational Study in France
Authors: Claire Rivoisy, Benjamin Besse, Nicolas Girard, Bertrand Lioger, Jean-Francois Viallard, Jean-Christophe Lega, Patricia Rullier, Antoinette Perlat, Delphine Lerouge, Christelle Clement-Duchene, Mikael Ebbo, Annick Bosseray, Bertrand Godeau, Olivier Lambotte
Journal: Journal of Thoracic Oncology (2016)
Treatment of Leprosy
Authors: Paul W. Brand
Journal: New England Journal of Medicine (1956)

BEFORE the present decade, surgery on the patient with leprosy was mainly a retreating battle against advancing deformity. When ulceration of fingers or toes deepened to cause osteomyelitis, necrotic bone was removed. When ulceration became too widespread on the front of the foot, a partial amputation was performed. Higher amputations followed when the stumps themselves became destroyed. A few surgeons had attempted reconstructive surgery to the extent of excising nodules from ears and unsightly loose folds of skin from the face in arrested cases, to make it easier for the patients to rejoin society. Leprosy was regarded by most as . . .
Efficacy of pertussis vaccination in England. Report from the PHLS Epidemiological Research Laboratory and 21 area health authorities.
Journal: BMJ (1982)

A national assessment of the efficacy of pertussis vaccination was made in 21 area health authorities in England. Notification rates for children given either three doses of diphtheria/tetanus/pertussis vaccine or diphtheria/tetanus vaccine were studied during the two and a half-year period January 1978-June 1980. A survey of home circumstances showed that the two vaccine groups could be validly compared. Home visits were made to assess the severity of the illness, the attack rates in home contacts, and to take pernasal swabs. Pertussis vaccination was found to be of outstanding value in preventing serious disease. Nevertheless, its effect in controlling whooping cough is limited by the fact that protection for home contacts is less satisfactory, and by the occurrence of mild cases in vaccinated children which may contribute to the spread of the disease.
Abstract 16015: Acute Exposure to Air Pollution Triggers Ventricular Arrhythmias
Authors: Mark S Link, Heike Luttmann-Gibson, Joel Schwartz, Murray A Mittleman, Benjamin Wessler, Jennifer Nguyen, Diane R Gold, Douglas W Dockery, Francine Laden
Journal: Circulation (2013)

Background: Air pollution has been associated with cardiac events, including sudden cardiac death. However, the temporal association for acute events is not clear. In this prospective study we foll...
The antitumor activity of taxanes in prostate cancer is mediated through inhibition of AR nuclear accumulation and androgen-dependent signaling
Authors: B. P. Levy, M. Darshan, S. Jeske, X. K. Zhou, S. T. Tagawa, D. M. Nanus, P. Giannakakou
Journal: Journal of Clinical Oncology (2008)

16005 Background: Data suggest that androgen receptor (AR) signaling contributes to prostate cancer (PC) progression in patients with castrate resistant PC (CRPC) in the absence of ligand. Taxanes can inhibit PC progression and AR-driven PSA production in CRPC. We hypothesized that taxanes, by stabilizing microtubules, inhibit AR trafficking and nuclear accumulation thus, disrupting AR-signaling and inhibiting PC growth. Methods: LNCaP and/or PC3-AR cells were treated with taxanes ± the DHT analog R1181 (R). Tubulin, AR, PSA and PSMA proteins were analyzed by confocal microscopy or immunoblotting. AR's transcriptional activity was monitored by a PSA luciferase reporter plasmid assay. We used the CellSearch immunomagnetic capture technology (Veridex, NJ) to isolate circulating tumor cells (CTCs) from CRPC patients receiving docetaxel (DTX) chemotherapy. Results: Taxane treatment of PC cells resulted in the cytoplasmic sequestration of AR abrogating the androgen mediated AR translocation to the nucleus as a result of microtubule (MT) stabilization. In LnCAP cells transfected with PSA-Luc, taxane treatment inhibited AR's transcriptional activation of PSA in non-stimulated (C vs PTX, p=0.03) as well as R stimulated cells (R vs PTX/R, p=0.02). Taxane mediated inhibition of endogenous PSA was also observed. Inhibition of the MT- associated motor protein dynein also resulted in inhibition of ligand stimulated AR nuclear accumulation; further implicating MTs in the regulation of AR nucleo-cytoplasmic trafficking and subsequent gene transcription. High-resolution confocal imaging of PC patients’ CTCs revealed that: (1) AR associates with MTs in patients samples, (2) MT bundling accompanied by AR nuclear exclusion was observed in patients responding to DTX therapy (declining PSA and disease stabilization) and (3) non-affected MT network and intense AR nuclear accumulation was observed in patients progressing on DTX (rising PSA and clinical progression). These observations are being extended to additional CRPC patient samples. Conclusions: Collectively, our data suggest that taxanes’ anti-tumor effect in PC results from inhibition of nuclear accumulation of the AR downstream of microtubule bundling No significant financial relationships to disclose.
RNase H2 catalytic core Aicardi-Goutières syndrome–related mutant invokes cGAS–STING innate immune-sensing pathway in mice
Authors: Vladislav Pokatayev, Naushaba Hasin, Hyongi Chon, Susana M. Cerritelli, Kiran Sakhuja, Jerrold M. Ward, H. Douglas Morris, Nan Yan, Robert J. Crouch
Journal: The Journal of Experimental Medicine (2016)

The neuroinflammatory autoimmune disease Aicardi-Goutières syndrome (AGS) develops from mutations in genes encoding several nucleotide-processing proteins, including RNase H2. Defective RNase H2 may induce accumulation of self-nucleic acid species that trigger chronic type I interferon and inflammatory responses, leading to AGS pathology. We created a knock-in mouse model with an RNase H2 AGS mutation in a highly conserved residue of the catalytic subunit, Rnaseh2aG37S/G37S (G37S), to understand disease pathology. G37S homozygotes are perinatal lethal, in contrast to the early embryonic lethality previously reported for Rnaseh2b- or Rnaseh2c-null mice. Importantly, we found that the G37S mutation led to increased expression of interferon-stimulated genes dependent on the cGAS–STING signaling pathway. Ablation of STING in the G37S mice results in partial rescue of the perinatal lethality, with viable mice exhibiting white spotting on their ventral surface. We believe that the G37S knock-in mouse provides an excellent animal model for studying RNASEH2-associated autoimmune diseases.
Mischaracterizing social psychology to support the laudable goal of increasing its political diversity
Authors: Alice H. Eagly
Journal: Behavioral and Brain Sciences (2015)

Abstract Duarte et al.'s arguments for increasing political diversity in social psychology are based on mischaracterizations of social psychology as fundamentally flawed in understanding stereotype accuracy and the effects of attitudes on information processing. I correct their misunderstandings while agreeing with their view that political diversity, along with other forms of diversity, stands to benefit social psychology.
One-pot synthesis of pH-responsive hybrid nanogel particles for the intracellular delivery of small interfering RNA
Authors: Sm Z. Khaled, Armando Cevenini, Iman K. Yazdi, Alessandro Parodi, Michael Evangelopoulos, Claudia Corbo, Shilpa Scaria, Ye Hu, Seth G. Haddix, Bruna Corradetti, Francesco Salvatore, Ennio Tasciotti
Journal: Biomaterials (2016)

This report describes a novel, one-pot synthesis of hybrid nanoparticles formed by a nanostructured inorganic silica core and an organic pH-responsive hydrogel shell. This easy-to-perform, oil-in-water emulsion process synthesizes fluorescently-doped silica nanoparticles wrapped within a tunable coating of cationic poly(2-diethylaminoethyl methacrylate) hydrogel in one step. Transmission electron microscopy and dynamic light scattering analysis demonstrated that the hydrogel-coated nanoparticles are uniformly dispersed in the aqueous phase. The formation of covalent chemical bonds between the silica and the polymer increases the stability of the organic phase around the inorganic core as demonstrated by thermogravimetric analysis. The cationic nature of the hydrogel is responsible for the pH buffering properties of the nanostructured system and was evaluated by titration experiments. Zeta-potential analysis demonstrated that the charge of the system was reversed when transitioned from acidic to basic pH and vice versa. Consequently, small interfering RNA (siRNA) can be loaded and released in an acidic pH environment thereby enabling the hybrid particles and their payload to avoid endosomal sequestration and enzymatic degradation. These nanoparticles, loaded with specific siRNA molecules directed towards the transcript of the membrane receptor CXCR4, significantly decreased the expression of this protein in a human breast cancer cell line (i.e., MDA-MB-231). Moreover, intravenous administration of siRNA-loaded nanoparticles demonstrated a preferential accumulation at the tumor site that resulted in a reduction of CXCR4 expression.
Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab
Authors: Alexander Martens, Kilian Wistuba-Hamprecht, Marnix Geukes Foppen, Jianda Yuan, Michael A. Postow, Phillip Wong, Emanuela Romano, Amir Khammari, Brigitte Dreno, Mariaelena Capone, Paolo A. Ascierto, Anna Maria Di Giacomo, Michele Maio, Bastian Schilling, Antje Sucker, Dirk Schadendorf, Jessica C. Hassel, Thomas K. Eigentler, Peter Martus, Jedd D. Wolchok, Christian Blank, Graham Pawelec, Claus Garbe, Benjamin Weide
Journal: Clinical Cancer Research (2016)

To identify baseline peripheral blood biomarkers associated with clinical outcome following ipilimumab treatment in advanced melanoma patients.Frequencies of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), serum lactate dehydrogenase (LDH), routine blood counts, and clinical characteristics were assessed in 209 patients. Endpoints were overall survival (OS) and best overall response. Statistical calculations were done by Kaplan-Meier and Cox regression analysis, including calibration and discrimination by C-statistics.Low baseline LDH, absolute monocyte counts (AMC), Lin(-)CD14(+)HLA-DR(-/low)-MDSC frequencies, and high absolute eosinophil counts (AEC), relative lymphocyte counts (RLC), and CD4(+)CD25(+)FoxP3(+)-Treg frequencies were significantly associated with better survival, and were considered in a combination model. Patients (43.5%) presenting with the best biomarker signature had a 30% response rate and median survival of 16 months. In contrast, patients with the worst biomarkers (27.5%) had only a 3% response rate and median survival of 4 months. The occurrence of adverse events correlated with neither baseline biomarker signatures nor the clinical benefit of ipilimumab. In another model, limited to the routine parameters LDH, AMC, AEC, and RLC, the number of favorable factors (4 vs. 3 vs. 2-0) was also associated with OS (P < 0.001 for all pairwise comparisons) in the main study and additionally in an independent validation cohort.A baseline signature of low LDH, AMC, and MDSCs as well as high AEC, Tregs, and RLC is associated with favorable outcome following ipilimumab. Prospective investigation of the predictive impact of these markers following ipilimumab and other treatments, e.g., PD-1 antibodies, is warranted. Clin Cancer Res; 22(12); 2908-18. ©2016 AACR.
Long-term impact of developing a postoperative pulmonary complication after lung surgery
Authors: Sebastian T Lugg, Paula J Agostini, Theofano Tikka, Amy Kerr, Kerry Adams, Ehab Bishay, Maninder S Kalkat, Richard S Steyn, Pala B Rajesh, David R Thickett, Babu Naidu
Journal: Thorax (2016)

<h3>Introduction</h3> Postoperative pulmonary complications (PPC) such as atelectasis and pneumonia are common following lung resection. PPCs have a significant clinical impact on postoperative morbidity and mortality. We studied the long-term effects of PPCs and sought to identify independent risk factors. <h3>Methods</h3> A prospective observational study involved all patients following lung resection in a regional thoracic centre over 4 years. PPCs were assessed daily in hospital using the Melbourne group scale based on chest X-ray, white cell count, fever, purulent sputum, microbiology, oxygen saturations, physician diagnosis and intensive therapy unit (ITU)/high-dependency unit readmission. Follow-up included hospital length of stay (LOS), 30-day readmissions, and mortality. <h3>Results</h3> 86 of 670 patients (13%) who had undergone a lung resection developed a PPC. Those patients had a significantly longer hospital LOS in days (13, 95% CI 10.5–14.9 vs 6.3, 95% CI 5.9 to 6.7; p&lt;0.001) and higher rates of ITU admissions (28% vs 1.9%; p&lt;0.001) and 30-day hospital readmissions (20.7% vs 11.9%; p&lt;0.05). Significant independent risk factors for development of PPCs were COPD and smoking (p&lt;0.05), not age. Excluding early postoperative deaths, developing a PPC resulted in a significantly reduced overall survival in months (40, 95% CI 34 to 44 vs 46, 95% CI 44 to 47; p=0.006). Those who developed a PPC had a higher rate of non-cancer-related deaths (11% vs 5%; p=0.020). PPC is a significant independent risk factor for late deaths in non-small cell lung cancer patients (HR 2.0, 95% CI 1.9 to 3.2; p=0.006). <h3>Conclusions</h3> Developing a PPC after thoracic surgery is common and is associated with a poorer long-term outcome.