tbuckley/cabot-search huggingface dataset:
GPs demand extra funding for weekend emergency cover rather than routine care
Authors: Gareth Iacobucci
Journal: BMJ (2016)

GPs have urged the government to abandon its push for routine seven day services in primary care and instead to channel any additional funding into emergency cover at weekends.

Representatives at the BMA’s annual conference of local medical committees in London this week overwhelmingly backed a motion condemning the government’s push for seven day working as “unachievable, particularly in the light of the continued under-resourcing of primary care.”

The motion stated that the conference “insists that the seven day mantra be abandoned and …
Clinical risk factors for pre-eclampsia early pregnancy: problems with systematic review
Authors: Basky Thilagnathan
Journal: BMJ (2016)

We read Bartsch and colleagues’ review on clinical risk factors for pre-eclampsia with interest.1 This timely topic is of great clinical interest because it reworks the established institutional guidelines for using maternal characteristics to screen for pre-eclampsia risk in pregnancy. Although we applaud their diligent and meticulous approach, we have some reservations about this study.

The authors attributed specific risk thresholds to individual maternal risk factors in an attempt to allow clinicians to identify women who may benefit from aspirin …
Regeneration of Human Liver After Major Hepatectomy
Authors: G T PACK, A H ISLAMI, J C HUBBARD, R D BRASFIELD
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
Abstract B42: The sigma-2 receptor as a target for therapeutic drug delivery in triple negative breast cancer
Authors: Mehran Makvandi, Estifanos D. Tilahun, Brian P. Lieberman, Kuiying Xu, Chenbo Zeng, Catherine Hou, Robert H. Mach
Journal: Cancer Research (2016)

Abstract Introduction: Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer and typically results in poor patient prognosis. While other breast cancer subtypes benefit from targeted therapies, TNBC currently has no approved agents. The sigma-2 receptor has been validated as a proliferation marker and also a site for therapeutic drug delivery in ovarian and pancreatic cancer. In this study we evaluated the sigma-2 receptor as a target for therapeutic drug delivery in TNBC using a sigma-2 targeting vehicle conjugated to a small molecule activator of caspases(SMAC) mimetic, SW-IV-134. Methods: Triple negative breast cancer cell lines; MDA-MB-231, HCC1937 and HCC1806 were tested for sensitivity to sigma-2 targeted compound SW-IV-134 vs. Taxol or the deconstructed conjugate subparts. 2 hr and 48 hr treatments we assessed to determine whether there was a significant in vitro targeting effect. Sigma-2 expression was quantified through radioligand saturation studies using cell homogenate tissue and the Ki value of SW-IV-134 for the sigma-2 receptor was calculated through competitive inhibition studies. Caspase 3/7 activation was assessed after 2 or 48 hr treatments. Results: SW-IV-134 was the most potent treatment in MDA-MB-231 and HCC1937, while no difference from taxol was found in HCC1806. Sigma-2 receptor expression was found to be the highest in the MDA-MB-231 and no difference was found in HCC1937 and HCC1806. The Ki of SW-IV-134 for the sigma-2 receptor was 23 nM and is consistent with previously reported values. Caspase 3/7 activation was detected in all cell lines following treatment at 2 and 48 hr. The greatest caspase 3/7 activation was observed in the MDA-MB-231 cell line. Conclusion: The sigma-2 receptor is expressed at different levels on the three TNBC cell lines and the receptor expression corresponds to therapeutic efficacy. SW-IV-134 was the most potent therapeutic tested in two of the three cell lines with no difference between taxol observed in HCC1806. This study shows the sigma-2 receptor is a target that can be exploited for therapeutic drug delivery in three TNBC cell lines and may provide a platform for future targeted therapy development for TNBC. Citation Format: Mehran Makvandi, Estifanos D. Tilahun, Brian P. Lieberman, Kuiying Xu, Chenbo Zeng, Catherine Hou, Robert H. Mach. The sigma-2 receptor as a target for therapeutic drug delivery in triple negative breast cancer. [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 B42.
Resumption of Driving after Life-Threatening Ventricular Tachyarrhythmia
Authors: Toshio Akiyama, Judy L. Powell, L. Brent Mitchell, Frederick A. Ehlert, Christina Baessler
Journal: New England Journal of Medicine (2001)

Although the privilege of driving must be respected, it may be necessary to restrict driving when it poses a threat to others. The risks associated with allowing patients with life-threatening ventricular tachyarrhythmias to drive have not been quantified.
Abstract B02: The role of chromatin remodeler protein ARID1a in ovarian clear cell carcinoma
Authors: Ranjani Lakshminarasimhan, Claudia Andreu-Vieyra, Kate Lawrenson, Simon A. Gayther, Peter A. Jones, Gangning Liang
Journal: Cancer Research (2016)

Abstract Ovarian cancer is the fifth leading cause of cancer death among women in the United States and ovarian clear cell carcinoma (OCCC) is an aggressive subtype of epithelial ovarian cancer. Recent whole genome and whole exome sequencing studies have revealed that the chromatin remodeler protein AT-Rich Interactive Domain 1a (ARID1a) is frequently mutated in OCCC. ARID1a loss is also often observed in endometriosis which is strongly associated with OCCC. Consequently, we hypothesize that loss of ARID1a is an early step in transformation of endometriosis into OCCC. Here, we show that knocking down ARID1a in an immortalized endometriosis line, promotes greater invasion of basement membrane in vitro, and higher efficiency of anchorage-independent growth. Using two independent genome wide approaches to assay chromatin accessibility and DNA methylation, we demonstrate that the loss of ARID1a does not significantly alter global chromatin accessibility and DNA methylation with the exception of the genomic regions containing late replicating domains. Our findings do however indicate that the loss of ARID1a contributes to altered distribution of H3K27me3 and H3K27ac marks. Specifically we find an increased deposit of the polycomb repressive mark in the knock-down line outside of promoters. Interestingly, we also find the knock-down line has a higher level of the active mark H3K27ac at the promoters and a lower level at the enhancers relative to the scrambled control. Moreover, many of the genes differentially expressed upon ARID1a knock-down are consistent with the changes of H3K27ac at the respective gene promoter. We therefore conclude that loss of ARID1a expression contributes to cellular transformation through deregulation of gene expression primarily through alteration of histone marks. Citation Format: Ranjani Lakshminarasimhan, Claudia Andreu-Vieyra, Kate Lawrenson, Simon A. Gayther, Peter A. Jones, Gangning Liang. The role of chromatin remodeler protein ARID1a in ovarian clear cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B02.
Oliver Goldsmith
Authors: Joseph Garland
Journal: New England Journal of Medicine (1952)

OLIVER Goldsmith's place in literature is undisputed; his authenticity as a physician is more difficult to demonstrate, for his literary achievements stand out against a background of failure in practically everything else that he attempted. Born in 1728 in Ireland, in the hamlet of Lissoy, — possibly the "loveliest village of the plain," —the son of a Protestant clergyman of English descent, he was so shy and unattractive a youth as to be considered more than dull — "a stupid, heavy block-head," according to a contemporary estimate. He was, however, able to enroll in due time at Trinity College, in . . .
Cell surface GRP78 as a potential prognostic and predictive marker of breast cancer.
Authors: Rinat Yerushalmi, Karen Nalpandyan, Annat Raiter, Britta Hardy
Journal: Journal of Clinical Oncology (2014)

e22179 Background: Glucose-regulated protein (GRP78) is a key regulator of the unfolding protein response. Cancer cells overexpress GRP78, inducing its translocation to the cell surface. Little is known about cell surface GRP78 expression in breast cancer. The aim of this study was to assess the potential prognostic impact and predictive value of GRP78 expression in patients with early and locally advanced breast cancers. Methods: Cytoplasmic and cell-surface expression of GRP78 was examined in two patient groups: Group 1 - patients with operable T1,2, estrogen receptor-positive, node-negative cancer who were assessed with the Oncotype-DX gene profile in addition to the standard pathology assessment; Group 2 - patients mostly with locally advanced disease who received neoadjuvant systemic treatment. Association analyses were performed between GRP78 expression and prognostic variables of grade, estrogen receptor and progesterone receptor expression, and HER2 and Ki67 status. GRP78 values were compared between Group 1 , Group 2 before systemic treatment and Group 2 after systemic treatment. Results: The cohort included 48 patients, 21 in Group 2 (20 with locally advanced breast cancer). Rates of cell-surface GRP78 expression were 44% in Group 1, 4.8% in Group 2 before systemic treatment, and 23.8% in Group 2 after systemic treatment. The difference among the groups was statistically significant (p<0.003). This was not true for cytoplasmic GRP78 expression. Positive cell-surface GRP78 expression was associated with known good prognostic markers of high progesterone receptor expression (p=0.04) and low Ki67 percentage (p=0.018). There was a trend toward an inverse correlation between positive cell-surface GRP78 and the Oncotype-DX gene profile score, (p=0.11). Conclusions: Cell surface GRP78 positivity is a good prognostic marker in breast cancer and may serve as a potential marker of benefit from chemotherapy. Prospective studies of neoadjuvant treatment are needed using serial biopsies with a correlation to response in order to confirm these findings.
Alka-372-001: First-in-human, phase I study of entrectinib – an oral pan-trk, ROS1, and ALK inhibitor – in patients with advanced solid tumors with relevant molecular alterations.
Authors: Filippo G. De Braud, Monica Niger, Silvia Damian, Benedetta Bardazza, Antonia Martinetti, Giuseppe Pelosi, Giovanna Marrapese, Laura Palmeri, Giulio Cerea, Emanuele Valtorta, Silvio Veronese, Andrea Sartore-Bianchi, Elena Ardini, Antonella Isachi, Marcella Martignoni, Arturo Galvani, David Luo, Litain Yeh, Adrian Mario Senderowicz, Salvatore Siena
Journal: Journal of Clinical Oncology (2015)

2517 Background: Entrectinib (formerly RXDX-101) is a potent and selective oral small molecule inhibitor of the TrkA/B/C, ROS1, and ALK kinases. Schedule A (fasted, 4d on/3d off for 3wks, 1 wk rest) demonstrated significant antitumor activity (ASCO 2014). This abstract reports completion of Sch A and two other ongoing dosing schedules (B and C). Methods: Pts with advanced solid tumors with molecular alterations in TrkA, ROS1 or ALK were treated in Sch B (QD) or Sch C (4d on/3d off), both in fed state. Results: 31 pts were treated in Sch A (N=19), B (N=6), or C (N=6). In Sch A, doses > 800 mg/m2 did not increase exposure significantly. Thus, accrual in Sch A was closed. Various dose levels (mg/m2) were explored in Sch B [200 (n=3); 400 (n=3)] and Sch C [400 (n=3); 800 (n=3)]. 7 pts had objective responses: 6 PR, 1CR (see Table). We are the first to report clinical activity of a Trk inhibitor in a pt with NTRK1+ (encoding TrkA) CRC. Of 7 ROS1-rearranged evaluable/measurable NSCLC pts, 4 have had an objective response (ORR: 57%), with a median duration of 6+ months. Moreover, in ROS1 pts treated at ≥ 400 mg/m2, the ORR was 80% (4 of 5 pts). Entrectinib is well tolerated. The majority of pts reported G1/ G2 AEs. 13 pts reported ≥ G3 AEs. Asthenia and muscle weakness were possibly related ≥ grade 3 AEs (both reversible). No DLTs have been reported to date. In Sch A, entrectinib was readily absorbed and exposures increased dose-proportionally up to 800 mg/m2. In fed state, entrectinib exposures were approx. 2x compared to fasted state. Conclusions: In this trial with entrectinib administered in 3 different dosing schedules, significant antitumor response was observed in pts with relevant molecular alterations, notably ROS1-rearranged NSCLC at doses ≥ 400 mg/m2/day and the only NTRK1 rearranged pt treated to date. Accrual in Sch B and C continues until RP2D is achieved, followed by dedicated studies in selected tumor types. Clinical trial information: NCT02097810.Objective responses. Tumor type (alteration) Sch/Dose (mg/m2) Best Response Duration of Response (cycles) NSCLC (ALK) A/800 PR 10 NSCLC (ROS1) A/1200 PR 14+ C/400 PR 7+ C/400 CR 5+ B/400 PR 3+ CRC (NTRK1) A/1600 PR 3 Neuroblastoma (ALK) A/800 PR 9
Enhancement of Aspergillosis in Leukemic Chicken
Authors: E W CHICK
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
Discordant World Health Organization (WHO) Classifications In a Population-Based Study Of Adult Myelodysplastic Syndromes (MDS)
Authors: Erica D. Warlick, Phuong L. Nguyen, Rachel K. Fonstad, Adina Cioc, Betsy Hirsch, Jeffrey S. Miller, Daniel J. Weisdorf, Michelle A. Roesler, Julie A Ross
Journal: Blood (2013)
Phenethyldiguanide: A Dangerous Sideeffect
Authors: R. S. Walker, A. L. Linton
Journal: BMJ (1959)

<h3>Objective</h3> The overexpression of long noncoding RNA HOTAIR is associated with various aggressive solid carcinomas. However, its relationship with endometrial carcinoma has not been reported. The present study aimed to investigate the expression of the long noncoding RNA HOTAIR in endometrial carcinoma, its relationship with the carcinoma’s clinicopathologic features, and the biological function of HOTAIR in regulating endometrial cancer cell proliferation and invasion in vitro and in vivo. <h3>Methods</h3> The expression of HOTAIR was detected in different tissues and cell lines by real-time PCR. Lentivirus-mediated HOTAIR-specific shRNAvectors were transfected into endometrial cancer HEC-1A cells. Cell proliferation and colony formation were examined by CCK-8 assays and colony formation assays, respectively. Invasion and migration were examined by Transwell assays. Flow cytometry assay was used to examine the cell cycle. In addition, xenograft model assays were performed to analyze the growth of endometrial cancer cells in vivo. <h3>Results</h3> Our data showed that HOTAIR expression was higher in endometrial cancer cells and tissues than in normal endometrial tissues. HOTAIR expression was closely related to the tumor stage (<i>P</i> = 0.045), myometrial invasion (<i>P</i> = 0.014), and lymph node metastasis (<i>P</i> = 0.033). The down-regulation of HOTAIR resulted in a significant inhibition of cell proliferation, migration, and invasion and in cell cycle arrest at the G0/G1 phase. Furthermore, HOTAIR depletion significantly suppressed the endometrial cancer tumorigenesis in vivo. <h3>Conclusions</h3> This study is the first to suggest that HOTAIR plays an important role in the carcinogenesis of endometrial cancer. Targeting HOTAIR may be a novel therapeutic strategy for endometrial cancer.
Case 46-1980
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Gordon L. Snider, Eugene J. Mark
Journal: New England Journal of Medicine (1980)

Presentation of CaseA 38-year-old woman was admitted to the hospital because of a pulmonary infiltrate.She was well until eight years earlier, when bloody diarrhea occurred and a diagnosis of ulcerative proctitis was made. Sulfasalazine was prescribed; after a course of seven weeks the Stevens–Johnson syndrome developed, accompanied by a dry cough and dyspnea. Prednisone was given, with recovery. Asthma developed subsequently. Seven and a half years before admission a barium-enema examination showed a slight decrease in haustral markings in the distal transverse and descending colon, with a suggestion of mucosal thickening in the splenic flexure; no ulcers were . . .
European versus U.S. data on the course of schizophrenia
Authors: J Marengo, M Harrow, J Sands, C Galloway
Journal: American Journal of Psychiatry (1991)

The present research attempts to add to the existing body of data on the course of schizophrenia by comparing the findings of a prospective study of a group of U.S. schizophrenic patients with data from two European studies.Seventy-four U.S. patients given the diagnosis of schizophrenia according to Research Diagnostic Criteria were longitudinally assessed at hospitalization and at three intervals up to 10 years after illness onset. The longitudinal criteria for type of onset, course of illness, and outcome were derived from the European studies of Manfred Bleuler and Luc Ciompi. The type of onset, course of illness, and outcome of the U.S. patients were compared with those of the patients in the two European studies.A lower rate of acute onset and of episodic illness was found in the U.S. patients, but the relative frequency of a number of major overall course patterns was similar across studies.Despite many potential threats to comparability, the results of the European and U.S. longitudinal studies of the course of schizophrenia were fairly congruent in terms of the relative rate with which patients fell into the categories established by Bleuler and Ciompi. These results are encouraging in that they point to the possibility of estimating the rate of occurrence of particular expressions of the overall course of schizophrenia.
Abstract 18841: Outcomes of Septal Myomectomy in the United States: A 13-year perspective
Authors: Sidakpal S Panaich, Kathan Mehta, Nileshkumar J Patel, Neeraj Shah, Ankit Chothani, Peeyush Grover, Vikas Singh, Ankit Rathod, Sadip Pant, Vipulkumar Bhalara, Ghanshyambhai T Savani, Abhishek Deshmukh, Jay L Mehta, Apurva O Badheka
Journal: Circulation (2013)

Background: Septal Myomectomy (MM) is the primary modality for left ventricular outflow tract (LVOT) gradient reduction in hypertrophic obstructive cardiomyopathy (HOCM) patients with refractory symptoms. Extended follow-up data for MM from a large multi-center registry is sparse. METHODS: We queried the Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample (NIS) between 1998 and 2010 using ICD9 procedure code 37.33 for MM. Only adult patients with HOCM (ICD-9-CM code 425.1) were included. Out of these, patients with any arrhythmia diagnosis were excluded. The NIS represents 20% of all hospitals in the US. We defined severity of co-morbidities using Deyo modification of Charlson co-morbidity index (CCI), where higher scores (0-33) represent increasing burden. Three level hierarchical mixed models were created to identify independent multivariate predictors of complications and mortality for MM. Hierarchical mixed effects linear regression models were used to evaluate cost of hospitalization and length of stay (LOS). RESULTS: The overall mortality was 5.9%. 5.4% of the patients had significant post-operative bleeding necessitating transfusion while 8.7% had complete heart block requiring a pacemaker. Increasing CCI was associated with a higher rate of complications and mortality (OR 2.42, 95% CI (1.17-4.98), p-value 0.02). The mean cost of hospitalization was $40,444 +/- 1,786 while the average LOS was 8.69 +/- 0.35 days. Occurrence of any post-operative complications was associated with an increased cost of hospitalization (+$33,870, p&lt;.01) and LOS (+6.1 days, p&lt;.01). Conclusions: We observed a relatively higher mortality rate for surgical MM than published literature with cardiac complications being most common specifically complete heart block. Increasing severity of co-morbidities was predictive of poorer outcomes while a higher burden of post-operative complications was associated with a higher cost of hospitalization and LOS.
Utilization of diabolo-shaped covered biliary stents in a refractory esophagus-colonic anastomotic stricture
Authors: Rolando Pinho, Luísa Proença, Ana Ponte, Joana Silva, Jaime Rodrigues, Mafalda Sousa, João Carvalho
Journal: Endoscopy (2016)

A 54-year-old man underwent a proximal gastrectomy with partial esophagectomy to treat a carcinoma of the cardia 5 years ago. A persistent postoperative fistula of the esophago-gastric anastomosis occurred, which required a second surgery 4 years ago during which a colon interposition was performed. After surgery, stricture of the esophagus-colonic anastomosis developed 2 cm distal from the upper esophageal sphincter, causing grade 3 dysphagia for which the patient underwent multiple dilations with Savary–Gilliard bougies. As the stenosis was deemed refractory to serial dilations, a biodegradable esophageal stent (BD stent 019-10A-23/18/23-060; SX-ELLA, Hradec Kralove, Czech Republic) was placed 1 year ago ([Fig. 1]).
Case 16-2016
Authors: Dwight J. Rouse, Thomas W. Keimig, Laura E. Riley, Alyssa R. Letourneau, Mia Y. Platt
Journal: New England Journal of Medicine (2016)

A 31-year-old woman who was pregnant with dichorionic, diamniotic twins presented at 35 weeks of gestation with fever, rigor, malaise, myalgias, anorexia, and loose stools. A chest radiograph revealed patchy right basilar opacities. Diagnostic test results were received.