tbuckley/cabot-search huggingface dataset:
AT-101, a small molecule Bcl-2 antagonist, in treatment naïve CLL patients (pts) with high risk features; Preliminary results from an ongoing phase I trial
Authors: D. F. James, J. E. Castro, O. Loria, C. E. Prada, R. A. Aguillon, T. J. Kipps
Journal: Journal of Clinical Oncology (2006)

6605 Background: CLL pts with early stage disease are often observed under a “watch and wait” approach. Unmutated immunoglobulin variable-region gene (Ig VH ); expression of zeta chain associated kinase (ZAP-70); CD38 expression; and cytogenetics abnormalities identify pts with a tendency for early disease progression. Whether pts with these high-risk features may benefit from early intervention warrants investigation in clinical trials. Gossypol, a naturally occurring compound in cotton seeds has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R-(-)-gossypol binds to Bcl-2 family proteins and induces apoptosis of CLL cells in vitro. Dysregulated expression of Bcl-2 proteins is critical for CLL leukemogenesis and is an attractive therapeutic target. Methods: We conducted a phase I study to evaluate the safety and tolerability of single agent AT-101 in treatment naïve CLL pts with high-risk features. Clinical activity, pharmacokinetics, and pharmacodynamics were assessed. Results: 7 pts were treated with AT-101 at doses of 20–40mg daily. Pt characteristics: median age 55, median Rai stage II, elevated ZAP-70 (57%), high CD38 (71%), unmutated Ig VH (57%), trisomy 12 (43%), and loss of 17p (43%). AT-101 was well tolerated with no grade 4 toxicities, hospitalizations, deaths. Maximum toxicity in 6 evaluable pts was grade III transaminase elevation at week 7, with complete resolution following discontinuation of AT-101. Other most common adverse events, all Grade 1–2 include: elevated transaminases; nausea; fatigue; diarrhea; and hypokalemia. No hematologic toxicity was observed. 5/6 pts had decrease in lymphocyte count, 6/6 had reduction in lymphadenopathy, and 5/5 with palpable spleens had reduction in spleen size. Cmax for 30mg (n=3) and 40mg (n=2) dose of AT-101 was 570ng/ml and 660ng/ml at a Tmax of 4.3 and 4.4 hrs. Tmax correlated with in vivo apoptosis studies revealing maximum leukemic cell apoptosis occurring at 4hrs and poly(ADP-ribose) polymerase cleavage. Conclusions: AT-101 is safe and well tolerated, induces in vivo leukemia cell apoptosis, and may have clinical activity in previously untreated pts with CLL and high risk features. No significant financial relationships to disclose.
Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050
Authors: Brien A. Holden, Timothy R. Fricke, David A. Wilson, Monica Jong, Kovin S. Naidoo, Padmaja Sankaridurg, Tien Y. Wong, Thomas J. Naduvilath, Serge Resnikoff
Journal: Ophthalmology (2016)

PurposeMyopia is a common cause of vision loss, with uncorrected myopia the leading cause of distance vision impairment globally. Individual studies show variations in the prevalence of myopia and high myopia between regions and ethnic groups, and there continues to be uncertainty regarding increasing prevalence of myopia.DesignSystematic review and meta-analysis.MethodsWe performed a systematic review and meta-analysis of the prevalence of myopia and high myopia and estimated temporal trends from 2000 to 2050 using data published since 1995. The primary data were gathered into 5-year age groups from 0 to ≥100, in urban or rural populations in each country, standardized to definitions of myopia of −0.50 diopter (D) or less and of high myopia of −5.00 D or less, projected to the year 2010, then meta-analyzed within Global Burden of Disease (GBD) regions. Any urban or rural age group that lacked data in a GBD region took data from the most similar region. The prevalence data were combined with urbanization data and population data from United Nations Population Department (UNPD) to estimate the prevalence of myopia and high myopia in each country of the world. These estimates were combined with myopia change estimates over time derived from regression analysis of published evidence to project to each decade from 2000 through 2050.ResultsWe included data from 145 studies covering 2.1 million participants. We estimated 1406 million people with myopia (22.9% of the world population; 95% confidence interval [CI], 932–1932 million [15.2%–31.5%]) and 163 million people with high myopia (2.7% of the world population; 95% CI, 86–387 million [1.4%–6.3%]) in 2000. We predict by 2050 there will be 4758 million people with myopia (49.8% of the world population; 3620–6056 million [95% CI, 43.4%–55.7%]) and 938 million people with high myopia (9.8% of the world population; 479–2104 million [95% CI, 5.7%–19.4%]).ConclusionsMyopia and high myopia estimates from 2000 to 2050 suggest significant increases in prevalences globally, with implications for planning services, including managing and preventing myopia-related ocular complications and vision loss among almost 1 billion people with high myopia.
Abstract 11960: Abnormal Ca2+ Dynamics Underlies Triggered Activity in a Rabbit Model of Long QT Syndrome. Analysis of Subcellular Data From a Beating Heart
Authors: Jong Kim, Jan Nemec, Guy Salama
Journal: Circulation (2013)

Background: Delayed afterdepolarizations (DADs) are caused by spontaneous release of Ca2+ from overloaded sarcoplasmic reticulum (SR), which propagate through myocytes as a Ca2+ waves. Increased cy...
Intrapericardial Teratoma
Authors: Maurice Beghetti, Mark Prieditis, Ivan M. Rebeyka, John Mawson, None FRACR
Journal: Circulation (1998)

A 1-month-old boy presented with signs of heart failure and tamponade.Two-dimensional echocardiography revealed a complex mass with a large pericardial effusion compressing the heart.Magnetic resonance imaging (Fig 1) defined the relationship of the mass to the pericardium, myocardium, and great vessels.Complete surgical resection was performed without complication (Fig 2).Histology of the mass confirmed the presumptive imaging diagnosis of teratoma.The patient remains free of symptoms and tumor 1 year after surgery.Intrapericardial teratomas are rare primary cardiac tumors usually diagnosed in neonates and infants. 1,2They contain endodermic, mesodermic, and neuroectodermic germinal layers. 3Intrapericardial teratomas are usually benign tumors but may be life-threatening because of large pericardial effusion and cardiac compression. 1,2Echocardiography generally suggests the diagnosis by showing a heterogeneous intrapericardial mass associated with a pericardial effusion compressing the heart. 2 Two-dimensional echocardiography is considered to be the best diagnostic imaging modality for primary cardiac tumors, but magnetic resonance imaging may have advantages with large tumors in defining the relationship of the tumor to adjacent structures, in visualizing echocardiographic "blind" spots, and in defining tissue characteristics.
Environmental tobacco smoke (ETS) in allergic asthma: A parallel exposure study in human subjects and sensitized allergic Balb/c mice
Authors: Martin Gaisberger, Heidemarie Dobias, Romana Mikes, Fikreta Grabcanovic-Musija, Bernd Lamprecht, Weiss Gertraud, Renata Sanovic, Arnulf Hartl, Michael Studnicka
Journal: European Respiratory Journal (2011)

Introduction:  The present study focused on the acute effects of short term (3 hours) exposure to ETS in allergic asthma, in a mouse model as well as in asthmatics.   Methods:  Analogously 23 non-smoking asthmatics as well as 54 allergen challenged Balb/c mice were exposed to artificially produced ETS in increasing concentrations (I=250 μg/m 3 , II= 450 μg/m 3 , III=850 μg/m 3 ) or to ambient air (control group).  In human asthmatics, lung function, exhaled NO and exhaled CO was assessed. Serum samples were analyzed for cytokine profile and distribution of immune cells. Symptom severity was assessed via asthma control test (ACT) and visual analogue scale (VAS) questionnaires.  Whole body plethysmography was performed in mice before, after and one day after ETS treatment. The immunological status of mice was assessed by analysing serum cytokines and BALF cell composition.   Results:  Human asthmatics exposed to ETS II and ETS III had significantly lower FeNO levels, a decrease in lung function of small airways (MEF25, MEF50) and an increase in VAS scores compared to controls. In sera ETS II led to a more antiinflammatory cytokine profile (IL10) whereas ETS III showed a proinflammatory cytokine milieu (IL8, TNF-α) compared to controls.  Airway hyperreactivity in mice exposed to ETS II and ETS III was increased. Provocation with metacholine resulted in similar hyperreactivity in both groups. However, control mice displayed an improved recovery after provocation compared to ETS III exposed animals.   Conclusion:  The data indicate a direct and dose dependent effect of ETS exposure on lung function as well as respiratory inflammation in human asthmatics and sensitized allergic mice.
Learning From the Past to Improve VA Health Care
Authors: Ashish K. Jha
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Gait modifications to change lower extremity gait biomechanics in runners: a systematic review
Authors: Christopher Napier, Christopher K Cochrane, Jack E Taunton, Michael A Hunt
Journal: British Journal of Sports Medicine (2015)

Background Abnormal biomechanics have been cited as a potential risk factor for running-related injury. Many modifiable biomechanical risk factors have also been proposed in the literature as interventions via gait retraining. Aim To determine which interventions have successfully modified biomechanical variables linked to running-related injury. Study design Systematic literature review. Methods MEDLINE, EMBASE, CINAHL, SportDiscus and PSYCINFO were searched using key terms related to running biomechanics and gait retraining. Quality of included studies was assessed using the modified Downs and Black Quality Index and a best evidence synthesis was performed. Results 27 studies investigating the effect of biomechanical interventions on kinetic, kinematic and spatiotemporal variables were included in this review. Foot strike manipulation had the greatest effect on kinematic measures (conflicting evidence for proximal joint angles; strong evidence for distal joint angles), real-time feedback had the greatest effect on kinetic measures (ranging from conflicting to strong evidence), and combined training protocols had the greatest effect on spatiotemporal measures (limited to moderate evidence). Conclusions Overall, this systematic review shows that many biomechanical parameters can be altered by running modification training programmes. These interventions result in short term small to large effects on kinetic, kinematic and spatiotemporal outcomes during running. In general, runners tend to employ a distal strategy of gait modification unless given specific cues. The most effective strategy for reducing high-risk factors for running-related injury—such as impact loading—was through real-time feedback of kinetics and/or kinematics.
Predictors of response to primary systemic therapy (PST) with docetaxel and trastuzumab in HER2-positive breast cancer
Authors: M. Rao, J. J. Griggs, L. M. Schiffhauer, P. Messina, P. Bourne, G. M. Ahrendt
Journal: Journal of Clinical Oncology (2007)

11100 Background: The purpose of this study was to assess the relationship between estrogen receptor (ER) status, amplification of HER-2, and tumor response to PST with docetaxel and trastuzumab in breast cancers positive for HER-2 by immunohistochemistry (IHC). Long-term disease-free survival data are also reported. Methods: Eligible patients were those with T2 or T3 tumors and overexpression of HER-2 via IHC. Docetaxel 100 mg/sq m q. 3 weeks × 4 with growth factor support and weekly trastuzumab × 12 were given before surgery. The Miller-Payne system was used to define pathologic responses (PR) in the excision specimen (0, 1, 2 - no/minimal response; 3 - 4 partial response, pPR; 5 - complete response, pCR). Adjuvant therapy was given at the discretion of the treating oncologist. Results: Of 22 enrolled patients, 19 were assessable. 17 of the 19 subjects had subsequent FISH confirmation of HER-2 status. Six subjects (31%) had a pCR. Of these, 5 had strong amplification of HER-2 and 5 had tumors that were ER-negative. A pPR occurred in an additional 2 subjects (10%). Of the 11 subjects who had no or minimal PR (Miller-Payne 0 - 2), 8 were found to have no amplification for HER-2 and 9 had tumors that were ER-positive. Postoperative (adjuvant) chemotherapy was given to 17 patients. All 12 patients with ER-positive tumors received adjuvant hormonal therapy. Three patients had an asymptomatic decline in left ventricular ejection fraction (LVEF) of 10 - 15% after anthracycline containing chemotherapy, and one had symptomatic non-ischemic cardiomyopathy of unclear etiology 4 years after completion of study therapy and an anthracycline. With a median follow up of 56 months, all 19 participants are alive and disease-free. Conclusion: PST with a 12-week course of trastuzumab and docetaxel is safe and effective, produces a substantial pCR rate, and may result in excellent long-term recurrence-free and overall survival. The subset of patients with tumors that were IHC-positive, but FISH-negative for HER-2, and ER-positive had minimal or no response to therapy, highlighting the importance of identifying patients most likely to respond to trastuzumab-based regimens. [Table: see text]
Does a training programme in chest drain insertion improve patient safety
Authors: Theodora Vatopoulou, Chirag Dave, Amanda James, Dwight McLeod
Journal: European Respiratory Journal (2011)

Introduction:  Following the National Patient Safety Agency alert for intercostal chest drain (ICD) insertion,our respiratory department introduced a training programme for all registrars (SpRs) & junior doctors. Emphasis was placed on completing a proforma at the time of insertion & notifying our team, so that subsequent closer monitoring of the ICD management occurred.   Methods:  A retrospective study of 52 consecutive ICD insertions notified at Sandwell Hospital over a year (Jan09-Jan10, males 80%, median age 67 years) was conducted. Indications for drainage,technique,documentation & complications were audited. The results were compared with a previous departmental 6 month audit.   Results:  Medical SpRs inserted 12(23.07%), respiratory SpRs & senior house officers (SHOs) 24 (46.15%), other SHOs 3 (5.7%), consultants 6 (11.5%), house officers 1 (1.9%) & in 6 (11.5%) the grade was unknown. 21 (40%) were inserted out of hours, 22 (42%) on the respiratory ward. Type of drain: 49 Seldinger (94.2%), 2 blunt dissections (3.8%), 1 pigtail (1.9%). All indications were according to British Thoracic Society guidelines: 21 pneumothoraces (40%), 29 pleural effusions (55%) & replacing 2 blocked ICDs (5%). The average length of ICD in situ 3.4 days compared to 5.2 previously. Complications included 1 empyema & 3 drains fell out. In the earlier audit, complications included ICD insertion into a bulla, 1 insertion into the liver, 2 severe site infections & 2 re-admissions for empyema.   Conclusions:  ICD training programmes improve patient safety. As over half of ICDs are placed by non-respiratory junior staff, there is a continual need for training. However, this is not just about ICD insertion; post insertion care, prompted by the proforma reduces complications & length of ICD stay.
Treatment of adults with recurrent progressive low-grade glioma using imatinib mesylate and hydroxyurea
Authors: M. E. Salacz, A. Desjardins, J. A. Quinn, J. N. Rich, J. J. Vredenburgh, S. Sathornsumetee, K. Goli, H. S. Friedman, D. A. Reardon
Journal: Journal of Clinical Oncology (2008)

2071 Background: Based on the encouraging activity and low toxicity of imatinib mesylate and hydroxyurea among adults with recurrent malignant glioma, we evaluated this combination among patients with recurrent/progressive low-grade gliomas (LGG). Methods: Key eligibility criteria for this phase II study included age over 18 yrs; histologically confirmed grade II LGG that is recurrent/progressive following at least prior surgical resection; Karnofsky 60% and adequate organ function. Imatinib plus hydroxyurea are given daily for 28 day cycles; imatinib is administered at 400 mg daily to patients not on CYP3A-enzyme inducing antiepileptic drugs (EIAED) while those on EIAED receive 500 mg twice a day. All patients receive 500 mg twice a day of hydroxyurea. Patients are evaluated every other month with physical and MRI examinations. Results: Enrollment includes 29 patients with astrocytoma and 26 with oligodendroglioma. Twenty-one (38%) are on EIAED. Median age is 44 years (range 20–74 years). Prior therapy had been given to 22 patients (40%) including (XRT, n=8; chemotherapy, n=14). Grade 3 toxicities were limited to neutropenia (n=5, 9%), fatigue (n=2, 4%) and diarrhea (n=2, 4%). Grade 4 events included neutropenia (n=1, 2%) and diarrhea (n=1, 2%). Among patients evaluable for response, 43 (78%) achieved stable disease and 5 (9%) had progression. Twenty-eight patients continue on study after 2–15 months of therapy. Accrual is nearly complete and follow-up is ongoing. Conclusions: Imatinib plus hydroxyurea administered on a continuous daily schedule is well tolerated and associated with encouraging preliminary activity among adults with recurrent/progressive LGG. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Genentech™ BioOncology
Skeletal-Related Events In Patients With Multiple Myeloma In The Era Of Novel Agents: Low Incidence Of Pathological Fractures After Treatment
Authors: Evangelos Terpos, Nikolaos Kanellias, Lia A Moulopoulos, Dimitrios Christoulas, Andreas Koureas, Tina Bagratuni, Vasilios Koutoulidis, Efstathios Kastritis, Meletios A. Dimopoulos
Journal: Blood (2013)
Inadequate activation of cortical motor areas during maximal and submaximal contractions of the knee extensors in COPD patients
Authors: François Alexandre, Nelly Héraud, Nicolas Oliver, Alain Varray
Journal: European Respiratory Journal (2013)

Introduction: COPD patients present anatomical alterations in the cerebral cortex and inadequate cortical responses during cognitive tasks (Dodd, J.W. et al. Am. J. Respir. Crit. Care Med. 2012; 186(3): 240-245). In addition, exercise intolerance could be modulated by central nervous system (Gagnon, P. et al. Am. J. Respir. Crit. Care Med. 2012; 186(7): 606-615). The hypothesis of cortical implication in the COPD loss of peripheral muscle force is highly relevant. This study thus sought to determine whether cortical motor areas are inadequately activated during lower-limb muscle contractions in COPD.

Methods: Fifteen COPD patients (GOLD 2 and 3) and fifteen sex/age-matched healthy controls were tested during maximal voluntary contractions (MVC) and 3 randomized submaximal contractions for 20 s at 10, 30 and 50% of MVC. Cortical activation was assessed through oxygenated hemoglobin concentration ([Oxy-Hb]) variations over premotor (CPM), prefrontal (PFC), primary motor (M1) and primary somatosensory (S1) cortical areas with multichannel near-infrared spectroscopy.

Results: Quadriceps strength (QMVC) was lower in patients (p<.05). M1\[Oxy-Hb] and PMC[Oxy-Hb] were significantly lower in patients during MVC and submaximal contractions (p<.05), except for 10 and 30% from PMC. QMVC variance was significantly explained by M1[Oxy-Hb] and PMC[Oxy-Hb\] (multiple r=0.76). S1[Oxy-Hb] and PFC[Oxy-Hb] showed no significant differences.

Conclusion: COPD patients exhibit selective inadequate activation of motor cortical areas during quadriceps contraction, which indicates that an impairment of central motor command is involved in the loss of muscle force production in COPD.
Osteopenia (OP) induced by 6 and 18 months androgen deprivation (AD)
Authors: J. Ball
Journal: Journal of Clinical Oncology (2007)

5123 Background: In a trial evaluating the optimal duration of AD in locally advanced prostate cancer (PC) we sought to determine whether 18 months of zoledronate (Zd) would reverse AD induced OP and reduce bony failure. Methods: In the four arm 2x2 TROG 03.04 (RADAR) trial, men with T2b,c-4 and T2a (Gleason score &gt;6, PSA &gt;10) N0 M0 PC (but without osteoporosis) were randomised to leuprotide (Lp) 22.5 mgs i.m. 3 monthly for 6 months starting 5 months prior to radiotherapy (RT) in Arm A, or the same treatment with Zd mgs i.v.i. 3 months for 18 months commencing on Day 1 (in Arms B and D), or with Lp 22.5 mg i.m. 3 monthly for 12 months after RT (in Arms C and D). Hip and spinal bone mineral densities (BMD) were measured before treatment (bt) and then at 2 and 4 years using DEXA and differences between trial arms were assessed by paired t tests. OP was defined by T- scores &lt;-1. Results: Between October 2003 and January 2006, 930 men were randomized. 124 men with BMD measures bt and at 2 years are evaluable. Mean change (±SD) in BMD between 0 and 2 years was -0.005 ±0.05 (p=0.57) in Arm A, 0.085 ±0.06 (p=&lt;0.001) in Arm B, 0.054 ±0.07 (p=&lt;0.001) in Arm C, and 0.065 ±0.05 (p=&lt;0.001) in Arm D. 98 men had normal BMD bt. Of these 6 of 51 in Arms A, C (no Zd) have developed OP at 2 years while none of 47 in Arms B, D (+Zd) have as yet. Conclusions: At 2 years OP caused by 6 months AD is minimal, but remains significant after 18 months AD. This is reversed by 18 months Zd, but further follow up will determine whether this degree of OP resolves with time or causes fractures. No significant financial relationships to disclose.