tbuckley/cabot-search huggingface dataset:
Cytogenetic correlation with efficacy on alemtuzumab (CAM) vs chlorambucil (CHLO) as front-line therapy for patients with progressive B-cell chronic lymphocytic leukemia (BCLL)
Authors: A. Dmoszynska, R. Fetni, Y. Wang, M. Belkaci, C. Sirard, M. Goldberg, J. Mayer, T. Robak, A. Skotnicki, P. Hillmen
Journal: Journal of Clinical Oncology (2006)

6601 Background: CAM307, a phase III, open-label, randomized comparative trial, enrolled 297 Rai stage I-IV BCLL patients with previously untreated, progressive disease requiring treatment. Patients were randomized to treatment with CAM (n=149) vs. CHLO (n=148) using standard dosing regimens. Methods: Cytogenetic assessment was conducted prior to the start of protocol-specified therapy. Chromosomal aberrations were detected by fluorescence in situ hybridization (FISH) using specific probes. Molecular cytogenetic analyses by FISH included deletions (del) 6q21, 6q telomere, 11q22–23, 13q14–14.3 and 17p13; trisomy bands of 8q24 and 12p11.1-q11.1. Results: A total of 271 patients have been evaluated. Chromosomal aberrations were detected in 207 patients (76%) while 64 patients (24%) exhibited normal karyotype. Cytogenetic abnormalities were evaluated by response [overall response rate (ORR) and complete response (CR)] to each therapy based upon an independent response review. The comparisons of ORR and CR between treatment arms for each mutation type were calculated using the Exact method. Conclusions: Preliminarydata demonstrate a statistically significant superior response to CAM in patients with del 13q (ORR and CR) and del 11q (ORR) as well as a statistically significant superior CR to CAM in patients with normal cytogenetics. In addition, although the sample size is small, there is a trend towards a better ORR in patients with del 17p. Further exploration of CAM response rates relative to cytogenetic abnormality is warranted. [Table: see text] [Table: see text]
In hospital rehabilitation units, adding individualized fall-prevention education to usual care reduced falls
Authors: Mark E. Williams, Nortin M. Hadler
Journal: Annals of Internal Medicine (2015)

Source Citation Hill AM, McPhail SM, Waldron N, et al. Fall rates in hospital rehabilitation units after individualised patient and staff education programmes: a pragmatic, stepped-wedge, cluster-randomised controlled trial. Lancet. 2015;Apr 9. Epub ahead of print. 25865864
Lessons from children: Wiser beyond their years
Authors: O. M McKendrick
Journal: BMJ (1998)

Karl was suffering from advanced cystic fibrosis and aged just 12 when he told a school friend that he was going to die. A few days later Karl was admitted to hospital and his absence from school led his friend to think this was because he had died. This information got back to Karl's mother who, feeling too upset to handle it, asked me if I would talk with him.

Karl was still in hospital when I received this request, so, picking a time when the ward was quiet, I asked him if he would like a talk. He said he would. I then asked him if he would like it here in bed or in my room. He …
Development of a new DNA topoisomerase I inhibitor, TP300: A pH-activated water-soluble prodrug
Authors: Mika Endo, Masako Ura, Hiromi Tanimura, Yoko Miyazaki, Masao Tsukazaki, Nobuo Shimma, Hisafumi Okabe, Masanori Miwa
Journal: Cancer Research (2007)

768  TP300 is a new camptothecin analogue, preclinically showing potent DNA topoisomerase I inhibitory activity, whilst also having potential for less individual variation, predictable PK, good availability in cancer cells and less influence by resistance mechanisms.  TP300 is a water-soluble prodrug administered using iv infusion in an acidic formulation (ca. pH 3-4). It is rapidly converted to the lipophilic active form (AF), CH0793076 at physiological pH. This pH dependent conversion means that production of AF is not subject to individual variation, as so commonly seen with prodrugs relying on enzymatic conversion. The lipophilicity of AF makes it more readily bioavailable to tumor cells.  TP300 showed statistically significantly greater tumor growth inhibition compared with CPT-11 (using maximum tolerated doses) in 11/12 mouse xenograft models, which included colorectal, lung, gastric and pancreatic cancer cell lines.  The effective dose range (MTD/ED50), calculated based on the HCT116 colon cancer mouse xenograft model, was 157 for TP300 and 12 for CPT-11, demonstrating a wider range of possible dosages for TP300.  In cancer chemotherapy, there is a major problem with the innate or acquired resistance of cancer cells to anticancer drugs. Breast cancer resistant protein (BCRP) expression is reported as a contributory factor to cellular resistance to camptothecin analogues, like SN-38. In a SN-38-resistant cancer cell line, containing various resistance mechanisms, including BCRP, a 55-fold higher concentration of SN-38 was needed to achieve IC50 compared with the parent cell line. This contrasted to an 8.5-fold difference for AF. To study BCRP resistance more specifically, a BCRP-transfected cell line was used and only a two-fold higher concentration of AF was needed to achieve IC50 in the presence of BCRP, compared with absence of BCRP, contrasting with a 12-fold difference for SN-38. These results show that the influence of BCRP upon AF is very limited. This in vitro activity, especially against BCRP-expressing cancer cell lines has also been clearly shown using some in vivo xenograft mouse models. In mouse xenograft models (12), TP300 showed similar activity in cancer cell lines with verified BCRP expression (4) or with negative or unknown BCRP expression (8), with more than 80% tumor growth inhibition in 11/12 cell line models. This compared with CPT-11 showing   There is also encouraging preclinical data in various combination settings.  A Phase I study is currently in progress.
Pituitary ablation for diabetic retinopathy.
Authors: J S Speakman, C B Mortimer, T D Briant, C Ezrin, W M Lougheed, W T Clarke
Journal: BMJ (1970)

Pituitary ablation was performed on 26 patients with advanced diabetic retinopathy by pituitary stalk section (nine patients) or transphenoidal hypophysectomy (17 patients). After a latent period varying from six to 12 months, retinal hemorrhages disappeared, vitreous hemorrhages stopped and new vessels regressed. Eight of 10 patients followed up for more than a year had a complete remission, although in one of two patients whose ablation was incomplete the retinopathy remained active. Preoperative visual acuity levels were preserved in 47 of 50 eyes of patients followed up for a mean period of 12 months. Three patients have died, two from causes related to their operation. Twenty of the survivors have continued in their usual occupation. Pituitary ablation is effective in preventing the progressive visual deterioration usually associated with advanced diabetic retinopathy.
Abstract 14444: Differential Effects of Nebivolol vs Metoprolol Succinate on Sympathetic Vasoconstriction During Exercise in Hypertensive Patients
Authors: Prafull Raheja, Zhongyun Wang, Debbie Arbique, Ronald Victor, Gail Thomas, Wanpen Vongpatanasin
Journal: Circulation (2011)

In normal physiologic states, sympathetic vasoconstriction is markedly blunted in exercising muscles to optimize blood flow to the metabolically active muscle. This phenomenon known as functional sympatholysis was shown to be mediated by nitric oxide (NO) and found to be impaired in the rodent model of angiotensin-induced hypertension via generation of oxidative stress, which inactivates NO. Recent studies from our laboratory confirmed presence of impaired functional sympatholysis in hypertensive patients during rhythmic handgrip exercise, resulting in augmented skeletal muscle ischemia. Nebivolol is a novel beta-adrenergic receptor blocker with NO releasing property. Whether nebivolol restores abnormal vascular function in hypertensive patients during exercise remains unknown. Therefore, we conducted studies in 20 hypertensive subjects in which we measured muscle oxygenation by near infrared spectroscopy and forearm blood flow (FBF) by Doppler ultrasonography in response to reflex increases in sympathetic nerve activity (SNA) evoked by lower body negative pressure (LBNP) at rest and during rhythmic handgrip exercise at 30% maximal voluntary contraction. These measurements were performed at baseline, after 12 weeks of nebivolol (5-20 mg/day), and after 12 weeks of metoprolol succinate (100-300mg daily), using a randomized crossover design. We found that nebivolol had no effect on LBNP-induced decreases in oxygenation and FBF in resting forearm (from -21.8 ± 5% to -18.0 ± 3% and from -27.4 ± 4% to -28.3 ± 4%, respectively; P > 0.05). However, nebivolol attenuated LBNP-induced reduction in oxygenation and FBF in exercising forearm (from -9.4 ±2% to -2.6 ± 2% and from -15.9 ±2% to -7.4 ± 2%, respectively, both p   0.05 vs baseline) despite similar reduction in resting BP. Nebivolol also had no effect on SNA at rest, during handgrip, or during handgrip plus LBNP, suggesting direct effect on vascular function. These data provide the evidence for nebivolol-induced restoration on functional sympatholysis in hypertensive humans, independent of BP reduction.
Americans are told to reduce sodium and increase potassium intake
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

Almost all Americans and Canadians consume too much salt and not enough potassium, increasing their risk of high blood pressure, stroke, coronary artery disease, and kidney disease, a report from the US Institute of Medicine says. The report was based on a comprehensive review of the scientific literature and was sponsored by a number of US and Canadian governmental organisations and foundations.

The report says unequivocally that blood pressure rises progressively as sodium intake increases. About 25% of Americans have high blood pressure, and more than half of people aged over 60 do.

Healthy adults aged between 19 and 50 years should consume 1.5 g of sodium (equivalent to 3.8 g of salt) a day to replace losses through perspiration but should not exceed 2.3 g (5.8 g of …
Full Uncapped Doses Of Chemotherapy In Non-Hodgkin's Lymphoma Patients With a High Body Surface Area Are Well Tolerated With No Increase In Toxicity, and a Trend Towards Improved Survival In Obese Patients
Authors: Sharon R. Jackson, Frcpa, Jessica Maree McLay, Angela Knox, Jae Hyun Lee, Sarah Wang, Samar Issa
Journal: Blood (2013)
Abstract 5171: EpCAM expression governs tumor growth or distant metastasis of human endometrial cancer: grow or go theory
Authors: Kuo-Chang Wen, Peng-Hui Wang, Pi-Lin Sung, Mong-Hong Lee, Cheng-Wen Wu
Journal: Cancer Research (2015)

Abstract Endometrial cancer is the most common gynecologic malignancy in United States. The prognosis is generally better because most patients are diagnosed at early stage. However, the overall survival rate declines to 10∼20% at advanced stage. There are no effective treatment in the management of patient with late stage of endometrial cancer or distant metastasis. EpCAM (also called TACSTD1 or CD326), a transmembrane glycoprotein, can mediate cell-cell adhesion. Its overexpression negatively correlates with clinical survival in gallbladder cancer, ampullary carcinoma, and squamous cell carcinoma of head &amp;. neck. However, a controversial role of EpCAM is reported in Lynch syndrome and rectal cancer as a tumor suppressor gene. To study the role of EpCAM in endometrial cancer, we manipulate the EpCAM expression in loss-of-function experiment in vitro; the results demonstrate that decrease of EpCAM expression is significantly related to increase invasion ability and diminish cell proliferation. These finding can be reversed after gain-of-function in EpCAM knock-down endometrial cancer cells. EpCAM knock-down is indeed linked to the cell signaling pathway of proliferation (regulation of cell proliferation GO:0042127, regulation of cell death:GO:0010941, regulation of apoptosis: GO:0042981) and migration (biological adhesion:GO:0022610, cell adhesion:GO:0007155, cell migration:GO:0016477) from microarray analysis. Significant more number of lymph node metastasis can be found in vivo at mice with IUI (intra-uterine injection) of EpCAM knock-down cells; moreover, smaller tumor size is observed in subcutaneously injected mice. Among the patients with endometrial cancer, the clinicopathologic characteristics, such as stage, lymph node metastasis, CA-125 value, and overall survival, are significantly related to the low EpCAM expression. Conclusively, diminishing EpCAM can promote endometrial cancer invasion; furthermore, the EpCAM expression is an significant prognostic factor in human endometrial cancer. These data has important implication that development targeting EpCAM in the treatment of endometrial cancer is the new application in future. Citation Format: Kuo-Chang Wen, Peng-Hui Wang, Pi-Lin Sung, Mong-Hong Lee, Cheng-Wen Wu. EpCAM expression governs tumor growth or distant metastasis of human endometrial cancer: grow or go theory. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5171. doi:10.1158/1538-7445.AM2015-5171
Genome-wide DNA methylation profiling of gastrointestinal neuroendocrine tumors to identify hypermethylation of mTOR, Wnt, and Notch pathways in GI NET pathogenesis.
Authors: Anna Karpathakis, Harpreet Dibra, Tiffany Morris, Dahmane Oukrife, Christodoulos P Pipinikas, Kerra Pearce, Joshua Francis, Marinos Pericleous, Dalvinder Mandair, Andrew Feber, Christos Toumpanakis, Tu Vinh Luong, Matthew Meyerson, Martyn E Caplin, Stephan Beck, Christina Thirlwell
Journal: Journal of Clinical Oncology (2014)

212 Background: Aberrant DNA methylation is known to play an important role in the pathogenesis of many human cancers, however little is known about its role in gastrointestinal neuroendocrine tumours (GI NET) development. We report the first unbiased genome-wide DNA methylation analysis of a large cohort of GI NETs, aiming to identify key methylation variable positions (MVPs) specific to GI NETs which may contribute to tumorigenesis and metastatic progression. Methods: Illumina Infinium Human Methylation 450 Array analysis was performed on 56 cases of GI NET DNA extracted from macrodissected tumour (n=67) and normal (n=29) specimens. Tumours were gastrointestinal primaries (n=39) or metastases (liver, mesenteric, omental or lymph node, n=28) of low (n=35), intermediate (n=17) or high grade (n=3)(unknown grade n=12). Data analysis was performed using the "ChAMP" custom pipeline and pathway analyses were performed using "GREAT," "WebGestalt," and "GSEA" web tools. A Bonferroni adjusted significance threshold value of p&lt;0.05 was used throughout. Results: In order to identify and validate a GI NET specific methylation signature our cohort was divided into a discovery set (31 cases) and validation set (25 cases). Comparison of primary GI NET tumours with normal small bowel identified a total of 77,916 MVPs, including 1,666 sites hypermethylated by over 30% in tumour compared to normal tissue. Application of the profile to the validation set correctly identified 85% of samples. Tumours demonstrated global hypomethylation relative to normal tissue. Gene ontology analysis identified methylation of multiple cancer related pathways (including the Wnt, mTOR and Notch pathways) as a feature of hepatic metastases of GI NET primaries. Increasing RASSF1 promoter hypermethylation was associated with higher tumour grade. Conclusions: This study is the first comprehensive analysis of the epigenetic profile of GI NETs and identifies potential novel biomarkers and therapeutic targets. We are currently performing integrated analysis of epigenomic, genomic and transcriptomic data to further define the pathways involved in GI NET pathogenesis.
Pain and Prejudice
Authors: Eric W. Fleegler, Neil L. Schechter
Journal: JAMA Pediatrics (2015)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Clinical significance of C reactive protein and MASTORA score in pulmonary embolism
Authors: Jolita Rackauskiene, Vaida Gedvilaite, Mindaugas Mataciunas, Mazvile Abrutyte, Olga Kusner, Edvardas Danila
Journal: European Respiratory Journal (2014)

Study aim:  To evaluate clinical significance of C reactive protein (CRP) and MASTORA score in acute pulmonary embolism (PE).   Materials and methods:  125 consecutive patients with newly diagnosed acute PE were prospectively examined. PE was confirmed by the chest CT angiography. D-dimer, CRP level tests, echocardiography and venous ultrasonography of the legs were performed. Risk factors were also explored. PE scope was evaluated using the MASTORA score.   Results:  D-dimer level   The higher MASTORA score had a strong correlation with higher D-dimer level (r=0.362, p  PE caused the death of two (1.6%) patients.   Conclusions:  D-dimer level
An Improved Biclustering Algorithm and Its Application to Gene Expression Spectrum Analysis
Authors: Hua Qu, Liu-Pu Wang, Yan-Chun Liang, Chun-Guo Wu
Journal: Genomics Proteomics & Bioinformatics (2005)

Abstract Cheng and Church algorithm is an important approach in biclustering algorithms. In this paper, the process of the extended space in the second stage of Cheng and Church algorithm is improved and the selections of two important parameters are discussed. The results of the improved algorithm used in the gene expression spectrum analysis show that, compared with Cheng and Church algorithm, the quality of clustering results is enhanced obviously, the mining expression models are better, and the data possess a strong consistency with fluctuation on the condition while the computational time does not increase significantly.
Of SCOTUS and Chicken
Authors: Larry Levitt
Journal: JAMA (2015)

essarily aware of evidence-based principles and how to use them to assess the literature themselves, they will still use evidence-based guidelines that lead to evidence-based practice.JAMA: Evidence-based medicine once was criticized as "cookbook medicine."Do you still encounter that kind of criticism, and if so, how do you counter it?DR GUYATT: One of my favorite talks to give is that evidence-based medicine is patient-centered medicine, so there are a number of things to point out.Perhaps most important is that evidence itself never tells you what to do, never.It's always evidence in the context of values and preferences.In other words, a person with one set of values and preferences will say, "Yes, it's the right thing."Another
Effectiveness of training session on the inhalation technique of the BA-pMDI Autohaler® (containing beclometasone) in daily practice
Authors: Antoine Magnan, Jean Marie Nguyen
Journal: European Respiratory Journal (2013)

Objective: To assess in daily practice the effectiveness of verbal instruction supplemented or not by written/video information to improve the inhalation technique of the BA-pMDI Autohaler® and identify factors that influence it.  Methods: This prospective, longitudinal, multicentric observational study was conducted in general practice. GPs assessed if patients inhalation technique with the breath-actuated metered-dose aerosol BA-pMDI Autohaler® was optimal (OT), otherwise trained them with: verbal instruction alone (VI), instruction with written advices (IWA) or instruction with video (IWV). They evaluated the results at inclusion and follow-up visit at 2 months.  Results: 667 asthmatic patients (mean age 43 ± 16 years) with non-optimal use of the BA-pMDI Autohaler® were trained with VI (36.5%), IWA (32.6%) or IWV (30.9%). OT average rate improved up to 84.2%: 80.9 % VI, 85.0% IWA and 87.5% IWV (NS). At the follow-up visit, OT rate stood at 74.1%: 70.7% VI, 70.8% IWA and 81.4% IWV (p: 0.0163) and was significantly higher in patients under 60 years (p  Conclusion: Asthmatic patients education significantly improves the inhalation technique of the BA-pMDI Autohaler® with an average OT rate of 84% after training, and a persistence rate over 70% after 2 months. The use of video permitted the persistence of an OT, especially in patients under 60 years.
Plasmodium vivax malaria in a Romanian traveller returning from Greece, August 2011
Authors: S A Florescu, C P Popescu, P Calistru, E Ceausu, M Nica, A Toderan, M Zaharia, P Parola
Journal: Eurosurveillance (2011)

In August 2011, a Plasmodium vivax malaria infection was diagnosed in a Romanian traveller returning from Greece. This case together with several reports over the past decade of autochthonous cases in Greece highlight that malaria should be considered as differential diagnosis in symptomatic travellers returning from this country. Travellers may serve as sentinels of emerging vector-borne diseases.
Abstract 18652: Phopshoinositide-Dependent Protein Kinase-1 Mediates Fasting Induced Autophagy in the Heart
Authors: Quan-Jiang Zhang, Adam R Wende, Yi Zhu, E. Dale Abel
Journal: Circulation (2010)

Fasting is a powerful inducer of cardiac autophagy, but the mechanisms are incompletely understood. The goal of this study was to determine if impaired insulin signaling via PI3K mediates fasting-induced autophagy. We characterized insulin signaling and markers of autophagy in control (WT) mice and mice with cardiomyocyte-restricted deletion of 3-phosphoinositide-dependent protein kinase-1 (PDK1) (PDKO). Consistent with loss of PDK1 signaling, basal Akt phosphorylation at Thr 308 was reduced by 67% and did not increase following in vivo insulin stimulation, however basal Akt phosphorylation at Ser 473 was preserved. In WT mice, fasting for 24 hr increased autophagy as evidenced by a 3.5-fold increase in LC3II/LC3I ratio (P<0.01 vs. Fed), a 60% increase in Cathepsin D level (P<0.01 vs. Fed), reduced p62 levels (P<0.05 vs. Fed), and increased AMPK phosphorylation (P<0.01 vs. Fed) that was associated with reduced mTOR, S6 and Foxo1/3 phosphorylation. In fed 6-week-old PDKO mice, similar changes in mTOR, S6 and FOXO1/3 phosphorylation were observed. The ratio of LC3II/LC3I was increased by 2-fold (P<0.01 vs. WT) and Cathepsin D level by 50% (P<0.05 vs. WT). p62 levels were reduced (P<0.05 vs. WT) and AMPK phosphorylation increased (P<0.05 vs. WT). In response to fasting, there was no further reduction of S6 or FOXO phosphorylation in PDKO mice but a further 25% increase in LC3II/LC3I ratios was observed. 6-week-old PDKO mice had significantly decreased heart weight (P<0.05 vs. WT), but LV contractile function was preserved. However, between 8–12 weeks of age, PDKO developed progressive heart failure characterized by LV dilatation, decreased wall thickness, increased fibrosis, and decreased fractional shortening resulting in death of all mice by 17-weeks of age. These data indicate that fasting-induced autophagy is largely regulated via PI3K-mediated signaling pathways. However, additional PI3K and mTOR independent pathways exist that contribute in part to fasting-induced autophagy. Second, chronic deficiency of PDK-1 signaling leads to progressive heart failure that may be due in part to unrestrained autophagy.