tbuckley/cabot-search huggingface dataset:
A phase I study of pemetrexed plus carboplatin or cisplatin with concurrent chest radiation therapy (CRT) for patients with locally advanced non-small cell lung cancer (LANSCLC)
Authors: J. H. Heinzerling, R. S. Hughes, R. Govindan, J. D. Bradley, J. Schiller, G. Peng, J. Treat, C. Obasaju, T. Tran, H. Choy
Journal: Journal of Clinical Oncology (2009)

7545 Background: Pemetrexed is a multi-targeted antifolate that inhibits the synthesis of both pyrimidines and purines. Pemetrexed is an effective new chemotherapeutic agent in advanced non-small cell lung cancer. Pemetrexed has also shown preclinical activity as a radiosensitizer in lung cancer. A phase I study was performed to establish the maximum tolerated dose (MTD) and phase 2 dose of carboplatin or cisplatin given with pemetrexed and CRT in LANSCLC. Methods: Patients (pts) with LANSCLC were enrolled. Initial intent was to establish the MTD of both weekly cisplatin and weekly carboplatin in combination with pemetrexed and CRT as an alternating two-arm phase I trial. Subsequently and based on early results from the CALGB 30407 trial (also evaluating the MTD of carboplatin), the protocol was amended to establish the safety of the planned phase II doses of cisplatin and carboplatin combined with pemetrexed 500 mg/m 2 and given every 3 weeks with concurrent CRT. Dose limiting toxicity (DLT) was defined as ≥ Grade 3 hematologic or nonhematologic toxicity based on Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. MTD was determined by occurrence of 2 DLTs among 6 pts in each cohort. Results: 22 pts were enrolled on 3 cohorts. All pts received pemetrexed, 9 with carboplatin AUC=2, 9 with cisplatin 30 mg/m 2 , and 4 with cisplatin 75 mg/m 2 . One DLT occurred in each of the carboplatin and cisplatin 30 mg/m 2 cohorts, prompting enrollment of 3 additional patients. No DLTs were seen in the cisplatin 75 mg/m 2 cohort. Conclusions: The MTD of cisplatin in combination with pemetrexed and CRT was not reached. Based on these results and those from CALGB 30407, either carboplatin AUC=5 or cisplatin 75 mg/m 2 in combination with pemetrexed 500 mg/m 2 given every 3 weeks with CRT appears to be well tolerated, and are currently being studied in a randomized phase II trial in pts with LANSCLC. [Table: see text]
Antibiotics for sore throats
Authors: C. Del Mar
Journal: BMJ (1995)

in childhood is therefore unlikely to be both sensitive (that is, identifying true positives) and specific (that is, not identifying non-cases as cases).This is especially so for schizophrenia of adult onset, which is characterised by abnormalities of cognition and behaviour not manifest in childhood.It is perhaps more important, however, to find out if and why potential cases either fail to develop schizophrenia or develop some disorder other than schizophrenia.Children with conduct disorders have been shown to be at high risk of alcohol and drug misuse and antisocial personality in adult life.' Whether the pattern of misconduct in these children differs or whether intervening events lead to different conditions remains to be determined.
Phase II trial of volasertib (BI 6727) versus chemotherapy (CT) in platinum-resistant/refractory ovarian cancer (OC).
Authors: Eric Pujade-Lauraine, Beatrice E. Weber, Isabelle Ray-Coquard, Ignace Vergote, Frédéric Selle, Jose Maria Del Campo, Jozef Sufliarsky, Inga Tschöpe, Pilar Garin Chesa, Serge Nazabadioko, Korinna Pilz, Florence Joly
Journal: Journal of Clinical Oncology (2013)

5504 Background: Volasertib (V) is a potent and selective cell cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinases. This study investigated V vs CT as 3 rd - or 4 th -line therapy in patients (pts) with platinum-refractory or resistant OC. Methods: Pts were randomized to V 300 mg IV Q3W or investigator’s choice single-agent CT (pegylated liposomal doxorubicin, topotecan, paclitaxel, gemcitabine) until progression or intolerance. Primary endpoint was 24-wk disease control rate (DCR; % of pts with complete/partial response [PR] or stable disease [SD]). Secondary endpoints included safety, progression-free survival (PFS), best overall response (RECIST 1.1) and explorative biomarkers. Results: 109 pts received V (n=54) or CT (n = 55) for a median (range) of 95 (22–716) and 114 (7–351) days, respectively. Demographic data were balanced between the treatment arms. Overall, median age was 62.0 yr; ECOG PS 0–1: 103 pts; 2 prior CTs: 51 pts; ≥3 prior CTs: 57 pts; platinum-resistant: 78 pts; platinum-refractory: 31 pts; measurable disease: 89 pts. 24-wk DCR (95% CI) for V vs CT was 31% (18–43) vs 43% (30–57), and median PFS was 13.1 vs 20.6 wks (HR = 1.01; 95% CI: 0.66–1.53). Six V pts vs 0 CT pts are ongoing for PFS 1 yr after randomization. Best overall response in pts with measurable disease (V/CT) was: PR, 7/8 pts; SD, 24/24 pts. Adverse events (AEs) led to discontinuation in 20 pts (V, n = 5; CT, n = 15); no V pts and 8 CT pts discontinued due to treatment-related AEs (including neuropathy in 3 CT pts). Most frequent all grade AEs (% of pts) regardless of relatedness were neutropenia (61%), anemia (54%), thrombocytopenia (46%), nausea (37%) and asthenia (33%) with V, and asthenia/nausea (47% each), abdominal pain (38%), anemia (36%) and neutropenia/vomiting (31% each) with CT. There were 3 fatal AEs per arm. Conclusions: Single-agent V showed antitumor activity in OC in a range similar to CT. AEs with V were mainly hematologic and manageable, with fewer non-hematologic AEs than CT. Exploration of potential predictive biomarkers for V activity is ongoing. Clinical trial information: NCT01121406.
Case 10-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Hasan Garan, Stephanie A. Horowitz
Journal: New England Journal of Medicine (1989)

Presentation of CaseA 60-year-old man was admitted to the hospital because of an intracardiac mass.There was a questionable history of a coronary attack 15 years earlier, characterized by "crushing" chest pain, for which he was treated in another hospital for one month. The patient recovered but experienced bouts of exertional chest pain that usually radiated to the left arm and episodes of exertional dyspnea and palpitations.Thirteen months before entry the exertional dyspnea worsened, and chest pain on exertion and palpitations became more frequent. He was admitted repeatedly to a second hospital because of recurrent chest pain, with . . .
Relationship Between Gout and Kidney
Authors: S L WALLACE, D BERNSTEIN
Journal: JAMA (1963)

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
MLL translocation in two castration-resistant prostate cancer (CRPC) patients.
Authors: Rajasree Pia Chowdry, Elisa M. Ledet, Mary C. Phelan, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2016)

186 Background: The mixed-lineage leukemia (MLL) protein is a histone methyltransferase that regulates multiple genetic elements. Chromosomal rearrangements of the MLL gene result in expression of MLL-fusion proteins that occur in a subset of acute leukemias and are associated with poor prognosis. The MLL protein complex has been shown to interact with the androgen receptor via the MLL-menin subunit and, in model systems, MLL-menin inhibition blocks CRPC growth. We describe 2 cases of metastatic CRPC with a translocation in the MLL gene. Methods: In our institution, fluorescence in situ hybridization (FISH) testing of bone marrow specimens is routinely performed using the MLL Breakapart probe from Cytocell, Ltd (Cambridge, UK). The probe consisted of an 87 kb segment labeled in red that covered a region telomeric to the MLL locus and a 168 kb segment labeled in green centromeric to MLL. The FISH assay was performed according to manufacturer’s instructions. Results: MLL translocation was found coincidentally in 2 patients. The first was a 50 year old male with CRPC who had progressed on abiraterone and multiple chemotherapy regimens. A bone marrow biopsy was done to evaluate pancytopenia and pathology revealed metastatic prostate cancer marrow infiltration, without any evidence of leukemia or myelodysplasia. FISH studies revealed a rearrangement of the MLL locus using the MLL Breakapart probe. The second patient was a 77 year old male with metastatic CRPC who had also progressed through multiple hormonal and chemotherapy regimens. Bone marrow biopsy was done to evaluate thrombocytopenia and pathology revealed metastatic prostate cancer occupying nearly 100% of the marrow. Cytogenetics revealed complex karyotype and FISH was positive for MLL gene rearrangement by the same assay. There was no evidence of leukemia or myelodysplasia in either case. Conclusions: Translocation of the MLL gene is well documented in leukemia but has not been described in CRPC. Additional studies are warranted regarding the frequency and importance of this potential therapeutic target.
THE VITAMIN CONTENT OF HUMAN MILK
Journal: JAMA (1927)

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
Asiatic acid inhibits lung cancer cell growth in vitro and in vivo by destroying mitochondria
Authors: Tiancong Wu, Ji Geng, Wenjie Guo, Jing Gao, Xixu Zhu
Journal: Acta Pharmaceutica Sinica B (2016)

Asiatic acid (AA), a pentacyclic triterpene found in Centella asiatica, displays significant anti-proliferative effects on cancer cells in vitro although the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer both in vivo and in vitro. Using the MTT assay, AA was found to induce apoptosis in a dose- and time-dependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3 (LC3) and decreased the expression of p62. Furthermore, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species (ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen (PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth both in vitro and in vivo and that the associated apoptosis is mediated through mitochondrial damage.
Seasonal affective disorder in the southern hemisphere
Authors: P Boyce, G Parker
Journal: American Journal of Psychiatry (1988)

To determine whether seasonal affective disorder exists in the southern hemisphere and whether there is any seasonal specificity in phenomenology, the authors compared 23 subjects who reported a winter/autumn affective disorder, consistent with earlier definitions of the syndrome, with 22 subjects who reported a spring/summer affective disorder. The subjects with winter/autumn onset were characterized by increased appetite, carbohydrate craving, and increased sleep; those with spring/summer onset reported decreased sleep and decreased appetite. Hypotheses concerning the etiology of seasonal affective disorder are discussed.
Multispectral Fluorescence Imaging During Robot-assisted Laparoscopic Sentinel Node Biopsy: A First Step Towards a Fluorescence-based Anatomic Roadmap
Authors: Nynke S. van den Berg, Tessa Buckle, Gijs H. KleinJan, Henk G. van der Poel, Fijs W.B. van Leeuwen
Journal: European Urology (2016)
Association of FoxP3 expression with worse outcomes in cholangiocarcinoma: Evidence to support the use of immunotherapy.
Authors: Richard Francis Dunne, Jennifer Findeis-Hosey, Laura Bratton, Nathania Figueroa, Brian Belt, Loralee McMahon, Andrew Shubin, Michael Lunt, Marcus Smith Noel, Mohamedtaki Abdulaziz Tejani, David Linehan, Aram F. Hezel
Journal: Journal of Clinical Oncology (2016)

e15631 Background: Cholangiocarcinoma (CC) is associated with a dense stroma comprised of an extracellular matrix, fibroblasts and tumor infiltrating leukocytes (TIL). Regulatory T-cells (Tregs), which express FoxP3, are a common component of TILs in other malignancies where they play a role in promoting antigen tolerance and immunosuppression. Treg prevalence has also proven to be an important prognostic biomarker and is predictive of response to checkpoint blockade therapies in other cancers. Their role has yet to be defined in CC. Here we characterize the association of Tregs with overall survival (OS) and various pathologic features. Methods: A tumor microarray (TMA) was constructed using 60 formalin-fixed paraffin embedded human CC samples and immunohistochemistry for T-cell markers (CD3, CD4, CD45, CD8, FoxP3) were performed. The TMA was scored by a single pathologist by measuring cell staining intensity. Univariate analyses comparing OS with pathologic tumor features and T-cell markers described were performed. We employed the Kaplan-Meier method to estimate the distribution of OS and compared survival curves using the log-rank test. The association of staining score and pathologic variables were tested using Fisher’s exact test for categorical variables. Results: 60 CC patients, chemotherapy naive at the time of biopsy (n = 8) or resection (n = 52), were evaluated retrospectively. Median age in years was 60 (range, 31-81y). 53 of 60 CC tumors (88%) stained positively for FoxP3. High tumor grade (poorly differentiated (PD) vs. well and moderate) (p = 0.007) and FoxP3 expression intensity (p = 0.03) were found to correlate negatively with OS. Increased FoxP3 expression was significantly associated with PD tumors (p = 0.01). No other T-cell marker was significantly associated with tumor grade or OS. Conclusions: FoxP3 expression is associated with a worse prognosis in CC. Furthermore, the link between FoxP3 and high grade CC suggests Tregs may be associated with more aggressive biology. These findings indicate that dampened T-cell immunity may contribute to adverse outcomes in CC. Immunotherapy targeting the T-cell response could be considered an attractive therapeutic strategy in CC.
Salmonella enterica sérotype Dublin en Autriche
Authors: F Allerberger, A Liesegang, K Grif, R Prager, J Danzl, F Höck, J Ottl, M P Dierich, C Berghold, I Neckstaller, H Tschäpe, I. S.T. Fisher
Journal: Eurosurveillance (2002)

En Autriche, le serotype Dublin de Salmonella enterica, adapte aux bovins, est rarement a l’origine d’infections humaines. En 2000, l’Autriche etait dans la moyenne europeenne, avec une incidence de 0,1 cas par million d’habitants. Nos donnees montrent que la grande majorite des infections dues au serotype Dublin, chez l’homme ou l’animal, sont epidemiologiquement liees a deux districts du Tyrol. Cette concentration de cas peut s’expliquer par un mode d’elevage du betail typique a cette region, les pâturages alpins. Le risque de contaminations croisees est accru par le regroupement d’animaux provenant de plusieurs fermes. Le betail infecte est une source de contamination pour les hommes, generalement par la consommation de viande de bœuf et de lait de vache. L’electrophorese en champ pulse et le ribotypage automatise ont permis de retrouver des clones caracteristiques de Dublin au Tyrol dans trois des cinq isolats a l’origine d’infections humaines. Pour empecher les contaminations croisees dans les grands troupeaux et la contamination des pâturages par du betail infecte de facon latente, il faudrait eventuellement commencer par proceder a un depistage bacteriologique du portage fecal avant la transhumance des troupeaux a risque vers les pacages de montagne, et avant le retour des animaux des pâturages a risque vers les fermes. Une recherche appropriee est necessaire.
Epratuzumab, a Humanized Monoclonal Antibody Targeting CD22
Authors: Josette Carnahan, Paul Wang, Richard Kendall, Ching Chen, Sylvia Hu, Tom Boone, Todd Juan, Jane Talvenheimo, Silvia Montestruque, Jilin Sun, Gary Elliott, John Thomas, John Ferbas, Brent Kern, Robert Briddell, John P. Leonard, Alessandra Cesano
Journal: Clinical Cancer Research (2003)

Purpose: Epratuzumab is a novel humanized antihuman CD22 IgG1 antibody that has recently shown promising clinical activity, both as a single agent and in combination with rituximab, in patients with non-Hodgkin’s lymphomas (NHL). In an attempt to better understand the mode of action of epratuzumab, the antibody was tested in vitro in a variety of cell-based assays similar to those used to evaluate the biological activity of other therapeutic monoclonal antibodies, including rituximab. In this report, we present epratuzumab activities as they relate to binding, signaling, and internalization of the receptor CD22.

Methods: Chinese hamster ovary-expressed CD22 extracellular domain was used to measure epratuzumab affinity on Biacore. CD22 receptor density and internalization rate were measured indirectly using a monovalently labeled, noncompeting (with epratuzumab) anti-CD22 antibody on Burkitt lymphoma cell lines, primary B cells derived from fresh tonsils, and B cells separated from peripheral blood samples obtained from patients with chronic lymphocytic leukemia or healthy volunteers. Epratuzumab-induced CD22 phosphorylation was measured by immunoprecipitation/Western blot and compared with that induced by anti-IgM stimulation.

Results: Epratuzumab binds to CD22-extracellular domain, with an affinity of K D = 0.7 nm. Binding of epratuzumab to B cell lines, or primary B cells from healthy individuals and patients with NHL, results in rapid internalization of the CD22/antibody complex. Internalization appears to be faster at early time points in cell lines than in primary B cells and NHL patient-derived B cells, but the maximum internalization reached is comparable for all B cell populations after several hours of treatment and appears to reach saturation at antibody concentrations of 1–5 μg/ml. Finally, epratuzumab binding results in modest but significant CD22 phosphorylation.

Conclusions: Epratuzumab represents an excellent anti-CD22 ligating agent, highly efficacious in inducing CD22 internalization, and can induce phosphorylation. Although we cannot unequivocally demonstrate here that epratuzumab-induced internalization and signaling of CD22 directly contribute to its therapeutic efficacy, these properties are the fundamental characteristics of the target CD22 and its interaction with epratuzumab. Similar results were observed when epratuzumab was tested in vitro on Burkitt B cell lines as well as on primary normal B cells and neoplastic B cells separated from fresh peripheral blood samples from patients with chronic lymphocytic leukemia.
Switching older people to a pill organiser could increase adverse events, researchers warn
Authors: Jacqui Wise
Journal: BMJ (2016)

Switching to a pill organiser could, somewhat surprisingly, cause older people to experience more adverse events, and patients should consult their GP or pharmacist before making this change, a health technology assessment has found.1

Pill organisers (or “medicine organisation devices”) have separate compartments for a patient’s medicines to be organised for the days of the week and times of day that they should be taken.

UK researchers from the University of East Anglia said that, although this finding from their small study seemed counterintuitive, patients may have previously taken their medicine …
Trends in the cost of the futile cancer care near the end of life.
Authors: Wender Lin, Chi-Jeng Hsieh
Journal: Journal of Clinical Oncology (2013)

126 Background: Aggressive cancer care near the end of life may not only represent a quality-of-care issue, but also a futility issue. Under the constraint of health resources, it is of interest to know the cost trends of futile treatment for cancer patients near the end of their life. Methods: The definition of potential medical futility for cancer patients near the end of their life was developed based on the RAND/UCLA Appropriateness Method. Nine experts or academics from medical, political, social, or legal fields built a consensus that treatment after 7 days in the intensive care unit following a cardiopulmonary resuscitation for cancer patients who died within 3 months is probably futile. Based on this definition, we used death registry and Taiwan’s National Health Insurance claim data from 2000-2001 and 2009-2010 respectively to estimate the cost of potential futile treatment for cancer patients near the end of their life in 2001 and 2010. Results: The percentage of cancer patients receiving potentially futile treatment near the end of their life reduced from 2.68% in 2001 (883/32,993) to 1.58% in 2010 (649/41,046). The cost of potentially futile cancer care also decreased from $283 million NTD (New Taiwan Dollar) in 2001 to $255 million NTD in 2010 (1USD=30NTD). Nevertheless, the per capita cost of potentially futile cancer care slightly increased from $320 thousand NTD to $393 thousand NTD. Conclusions: Although the cost of potentially futile cancer care for patients near the end of life is not huge in Taiwan, its trend of decrease may indicate that supportive but not aggressive cancer care is more and more prevailing and acceptable by patients, their family, as well as health care providers.
P-120 Gemcitabine + nab-paclitaxel as first-line chemotherapy for Japanese patients with advanced pancreatic cancer in real-world clinical practice: a retrospective study
Authors: T. Yamaguchi, H. Ueno, M. Sasaki, Y. Sakamoto, S. Kondo, C. Morizane, T. Okusaka
Journal: Annals of Oncology (2016)