tbuckley/cabot-search huggingface dataset:
Abstract 4261: Anti-angiogenic effects of zoledronic acid on osteotropic breast cancer cells
Authors: Cynthia Contreras, Walid Hamud, Bishal Dhakal, Bijay Khanal, Jason Bush
Journal: Cancer Research (2011)

Abstract Emerging data suggest the bisphosphonate, zoledronic acid (ZOL), exerts both indirect and direct anti-tumoral effects by decreasing tumor cell proliferation, increasing apoptosis, and inhibiting angiogenesis. Recent data indicate that anti-angiogenic factors exert cellular effects via suppression of mitochondrial oxidative phosphorylation/respiration and elevation of intracellular ROS levels. This project intended to define proteins involved in response to ZOL-treatment of an osteotropic breast cancer cell line, MDA-231BO. Results demonstrate that MDA-231BO cells are more sensitive to ZOL cytotoxicity and salutary effects are both media- and calcium-dependent. To investigate pro-apoptotic mechanisms of ZOL, total RNA, whole cell protein lysates, or mitochondrial-enriched fractions were isolated from MDA-231BO cells and using a combination of RT-PCR, 1D/2D-PAGE separation and MALDI-MS/MS, we identified several angiogenesis inhibitors that were upregulated and pro-angiogenic factors that were downregulated after ZOL treatment. Functional studies demonstrate the improved efficacy of ZOL on MDA-231BO compared to MDA-MB-231 controls. Taken together, these results further support a model that ZOL tips the ‘angiogenic switch’ in favor of anti-angiogenic factors in cancer cells with a propensity for bone metastases. Partial research support came from NIH 5P20MD002732 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4261. doi:10.1158/1538-7445.AM2011-4261
OCULISTS OR OPTOMETRISTS—WHICH?
Authors: JAMES M. PATTON
Journal: JAMA (1925)

I think we can state with perfect fairness that the majority of optometrists are in the main making an honest effort, through preliminary training and the establishment of definite standards of ethics and proficiency, to render service to the public. However, during the last five or six years there has been a growing activity on the part of certain optometrists, some of whom hold official positions in state optometric organizations, which can be interpreted only as an attempt to restrict the rights of the regularly licensed oculist so far as the fitting and prescribing of glasses is concerned, even looking forward to the time when all oculists will be compelled by law to pass an examination before the board of optometry of the state in which they may be located.  As several of these incidents have recently come to my notice, I wrote the attorney general of each of our
Human papillomaviruses in anogenital warts in children.
Authors: C J Lacey, P E Gibson, E C Benton
Journal: BMJ (1990)

and i blockers.But those who favour these drugs for first line treatment because of circumstantial evidence, as Professor Sever does, while disregarding the proved safety and efficacy of the older drugs in long term intervention trials threaten to return us to the dark ages of therapeutics.
Opiates in acute abdominal pain.
Authors: T J Hughes
Journal: BMJ (1979)

<h3>Background</h3> Deep brain stimulation (DBS) has proven to be a safe and effective therapy for refractory essential tremor, but information regarding long-term outcomes is lacking. <h3>Objectives</h3> We aimed to assess the long-term safety and efficacy of DBS in patients with essential tremor. <h3>Methods</h3> Patients treated with DBS for essential tremor for at least 8 years were evaluated in the ‘on’ and ‘off’ state using the Fahn–Tolosa–Marin tremor rating scale, and their medical records were reviewed to assess complications related to this therapy. <h3>Results</h3> We studied 13 patients (7 men): median age at evaluation 79 years (range 47–88), median age at electrode implantation 68 years (range 37–78) and mean time since electrode implantation 132.54±15.3 months (range 114–164). The difference between the ‘off’ and ‘on’ state on the motor items of the tremor rating scale was 41.9% (58.62 vs 34.08, p&lt;0.001) in the non-blinded and 37.2% (56.07 vs 35.23, p&lt;0.001) in the blinded rating. DBS provided a functional improvement of 31.7% in the ‘on’ state (15.07 vs 22.07, p&lt;0.001). A total non-blinded improvement in the tremor rating scale of 39% was observed in the ‘on’ state (49.15 vs 80.69, p&lt;0.001). Dysarthria and disequilibrium were common in patients with bilateral stimulation. A DBS-related surgery (electrode revision or internal pulse generator exchange) was necessary on average every 47.9 months to continue with the DBS therapy. <h3>Conclusions</h3> Thalamic DBS is a safe and effective therapy in patients with essential tremor followed for up to 13 years.
THE SIGNIFICANCE OF NON-OBSTRUCTIVE CORONARY ARTERY DISEASE UPON MULTI-DETECTOR COMPUTED TOMOGRAPHY IN PATIENTS PRESENTING WITH ACUTE CHEST PAIN
Authors: Roy Beigel, Sella Brosh, Orly Goitein, Einat Gutman, Amit Segev, Eli Konen, Dan Oieru, Hanoch Hod, Shlomi Matetzky
Journal: Journal of the American College of Cardiology (2012)
Hypoxia-Inducible Factor-1α and Excision Repair Cross-Complementing 1 in Patients with Small Cell Lung Cancer Who Received Front-Line Platinum-Based Chemotherapy: A Retrospective Study
Authors: Gyeong-Won Lee, Se IL Go, Yu Ji Cho, Yi Yeong Jeong, Ho-Cheol Kim, Jong Duk Lee, Young Sil Hwang, Gyung Hyuck Ko, Jeong Hee Lee, Dong Chool Kim, Jung Wook Yang, Sukjoong Oh, Jong Sil Lee
Journal: Journal of Thoracic Oncology (2012)
Adverse events reporting in English hospital statistics: Patients should be involved as partners
Authors: Joanne M Shaw, Melinda Letts, David Dickinson
Journal: BMJ (2004)

EDITOR—Dr Foster's case notes on adverse events in hospitals make alarming reading for patients.1 However, evidence shows that involving patients as partners in decisions about and management of drug treatment acts as a safeguard against errors.

Patients who understand their drug treatment are better placed to …
Receptor Imaging in Oncology by Means of Nuclear Medicine: Current Status
Authors: Bieke Van Den Bossche, Christophe Van de Wiele
Journal: Journal of Clinical Oncology (2004)

To date, our understanding of the role of receptors and their cognate ligands in cancer is being successfully translated into the design and development of an arsenal of new, less toxic, and more specific anticancer drugs. Because most of these novel drugs are cytostatic, objective response as measured by morphologic imaging modalities (eg, computed tomography or magnetic resonance imaging) cannot be used as a surrogate marker for drug development or for clinical decision making. Positron emission tomography (PET) can be used to image and quantify the in vivo distribution of positron-emitting radioisotopes such as oxygen-15, carbon-11, and fluorine-18 that can be substituted or added into biologically relevant and specific receptor radioligands. Similarly, single-photon emission computed tomography (SPECT) can be used to image and quantify the in vivo distribution of receptor targeting compounds labeled with indium-111, technetium-99m, and iodine-123. By virtue of their whole-body imaging capacity and the absence of errors of sampling and tissue manipulation as well as preparation, both techniques have the potential to address locoregional receptor status noninvasively and repetitively. This article reviews available data on the in vivo evaluation of receptor systems by means of PET or SPECT for identifying and monitoring patients with sufficient receptor overexpression for tailored therapeutic interventions, and also for depicting tumor tissue and determining the currently largely unknown heterogeneity in receptor expression among different tumor lesions within and between patients.
Tetanus prophylaxis in the A&amp;E department
Authors: K A Adeboye, O Sangowawa
Journal: Journal of the Royal Society of Medicine (2002)

In the UK, tetanus immunization began formally in 1961. Before then a few local programmes existed, and the Armed Forces were immunized from 1938. A sizeable part of the population is thus protected, and this fact should be reflected by limited use of booster doses of tetanus toxoid in accident and emergency departments. The official guideline1 says that, unless there is a tetanus-prone wound, there is little justification for booster doses in patients who have received a full course (five doses) in their lifetime. Behind this advice is the observation that, in the very rare cases where tetanus develops in the fully immunized, the disease is not severe. Of the 175 people who developed tetanus in England and Wales from 1984 to 20002, just 2 had been fully immunized according to their age and both survived (White J, PHLS, Personal communication). An additional reason for restraint is the risk of local reactions when further boosters are given.

Perhaps the guideline needs more publicity. We questioned 40 people (19 doctors, 21 nurses) working in AE and, of these, only 2 gave the correct answer to a question concerning the need for a booster after five doses. 8 of the 40 gave an answer consistent with the guideline in saying they would not give a booster to a fully immunized 30-year-old with a clean laceration. But, even for those who know it, the guideline does present practical difficulties. In younger patients, decisions for A&E staff will seldom be difficult, but a person born before the national immunization programme (i.e. over 40) may or may not have received all five recommended doses of toxoid, and is quite likely not to know. Of the 145 cases of tetanus (notifications, deaths and laboratory reports) between 1984 and 1995, 75% were in people over 45. If the patient has served in the Armed Forces, one can be more confident that full immunization has been given. Also to be considered are the large number of people who have immigrated to the UK from countries that lacked immunization programmes—Asia and Africa in particular. Even today, the take-up of formal immunization programmes is low in some parts of the world.

In an elderly population, Reid and co-workers3 found that 50% had tetanus antibody titres too low for protection. Low titres were very prevalent in the over-80s, especially women. In our opinion, all people who do not know their tetanus immune status should be encouraged to consult their general practitioners about the need for immunization. This includes many of the over-40s and people from the migrant population. Although the official guideline is clearly sound, there will be numerous occasions in the A&E department when toxoid must be given simply because of an uncertain immunization history. Over the years, these will diminish. For patients with tetanus-prone wounds, toileting and debridement will still need to be coupled with use of toxoid and also tetanus immune globulin.
Filgrastim‐mobilized peripheral‐blood stem cells can be stored at 4 degrees and used in autografts to rescue high‐dose chemotherapy
Authors: Guillermo J. Ruiz‐Argüelles, Alejandra Larregina‐Díez, Beatrlz Pérez‐Romano, Antonio Marín‐López, Alejandra Larregina‐Diez, M. Guadalupe Apreza‐Mollna
Journal: American Journal of Hematology (1995)

Abstract We studied 21 filgrastim (G‐CSF)‐mobilized peripheral blood stem cells (PBSC) apheresis products obtained from seven patients, and stored at 4°C for periods of up to 96 hr prior to their reinfusion, to rescue high‐dose chemotherapy. The apheresis products contained a median of 106 × 10/L mononuclear cells (MNC), 14.6% of them displaying the CD34 antigen; the viability was over 90% in all samples studied at 24, 48, and 72 hr after harvesting. These PBSC were successfully used to rescue high‐dose chemotherapy; patients received a median of 4.8 × 10/Kg MNC; the median time to achieve &gt;500 granulocytes was 14 days (range 11–26) and the median time to achieve &gt;20,000 platelets was 20 days (range 11–40). Since autologous transplants with nonfrozen PBSC are feasible and less costly than those using frozen PBSC, restrictions to PBSC autotransplant programs may be overcome and costs may be diminished.
Holidays in Framingham?
Authors: D. R Hadden
Journal: BMJ (2002)

It was a wet evening in May. We were driving into Boston from New Hampshire without definite plans on where to stay for the night. Suddenly a large motorway road sign loomed out of the mist: Route 9 West—Framingham. “I know that name,” I said, “Let's stay there: it would be interesting to see what sort of people are in the Framingham study, and what they eat.” So my wife and daughter agreed with my idea, for once.

It took some time, on a series of interconnecting highways, …
Hydrodynamic Gene Delivery: Its Principles and Applications
Authors: Takeshi Suda, Dexi Liu
Journal: Molecular Therapy (2007)

Efficient and safe methods for delivering genetic materials into cells must be developed before the clinical potential of gene therapy can be fully realized. Recently, hydrodynamic gene delivery using a rapid injection of a relatively large volume of DNA solution has opened up a new avenue for gene therapy studies in vivo. This method is superior to the existing delivery systems because of its simplicity, efficiency, and versatility. Wide success in applying hydrodynamic principles to delivery of DNA, RNA, proteins, and synthetic compounds, into the cells in various tissues of small animals, has inspired the recent attempts at establishing a hydrodynamic procedure for clinical use. In this review, we provide an overview of the theory and practice of hydrodynamic gene delivery so as to aid researchers for the use of this method in their pre-clinical and translational gene therapy studies. Efficient and safe methods for delivering genetic materials into cells must be developed before the clinical potential of gene therapy can be fully realized. Recently, hydrodynamic gene delivery using a rapid injection of a relatively large volume of DNA solution has opened up a new avenue for gene therapy studies in vivo. This method is superior to the existing delivery systems because of its simplicity, efficiency, and versatility. Wide success in applying hydrodynamic principles to delivery of DNA, RNA, proteins, and synthetic compounds, into the cells in various tissues of small animals, has inspired the recent attempts at establishing a hydrodynamic procedure for clinical use. In this review, we provide an overview of the theory and practice of hydrodynamic gene delivery so as to aid researchers for the use of this method in their pre-clinical and translational gene therapy studies.
Court lets BMA challenge government decision on GP pensions
Authors: Clare Dyer
Journal: BMJ (2007)

The BMA has been given the go ahead to take the government to court to challenge a decision to cap GPs' pensions.

The High Court has granted the BMA permission to apply for a judicial review of a decision by the former health secretary Patricia Hewitt to limit increases in family doctors' pensions, which the BMA argues breaches the new GP contract.

Hamish Meldrum, …
Coronary Responses and Differential Mechanisms of Late Stent Thrombosis Attributed to First-Generation Sirolimus- and Paclitaxel-Eluting Stents
Authors: Gaku Nakazawa, Aloke V. Finn, Marc Vorpahl, Elena R. Ladich, Frank D. Kolodgie, Renu Virmani
Journal: Journal of the American College of Cardiology (2011)
Consumer Income and Expenditures for Health Care
Authors: Edward M. Craft
Journal: JAMA (1969)

ABSTRACT The Consumer Price Index (CPI) illustrates that since 1950, physicians' fees have increased faster than the general price level. (See JAMA205:231-234 [July 22] 1968). In recent years these increases have accelerated. Since 1960, physicians' fees have increased at an annual rate approximately twice that of the general price level and per capita private expenditures for physicians' services have increased one and a half times that of consumers' disposable income.Inflation is a contagious phenomenon. As wages and prices increase in one sector of the economy, inflationary pressures are applied to wages and prices in other sectors. Physicians can be expected to react to inflationary forces in the same manner as do other employers. As the wages they pay to employees increase, and as other office expenses rise, they will probably increase their fees.In addition to the above inflationary pressures, prices have also been influenced by a rapid
Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial
Authors: Sayoki Mfinanga, Duncan Chanda, Sokoine L Kivuyo, Lorna Guinness, Christian Bottomley, Victoria Simms, Carol Chijoka, Ayubu Masasi, Godfather Kimaro, Bernard Ngowi, Amos Kahwa, Peter Mwaba, Thomas S Harrison, Saidi Egwaga, Shabbar Jaffar
Journal: The Lancet (2015)
Abstract B33: Intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a novel prodrug activator gene transfer technology in an immune-competent model of glioblastoma
Authors: Derek Ostertag, Karin Amundson, Taylor Buckley, Fernando E. Lopez, Bryan Martin, Harry Gruber, Walter Gunzburg, Omar Perez, Douglas J. Jolly, Joan M. Robbins
Journal: Clinical Cancer Research (2010)

Abstract Background: Patients with the most common and aggressive form of brain cancer, glioblastoma multiforme (GBM), have poor prognosis and current treatments remain only palliative. Previous gene therapy approaches using replication-deficient viral vectors have demonstrated limited efficacy likely due to poor gene delivery to the tumor. Methods: We used a novel replication-competent retroviral vector (Toca 511) designed and engineered to efficiently deliver a modified cytosine deaminase (CD) prodrug activating gene to glioma cells. Previous studies showed that such a replicating vector can preferentially infect intracranial human xenografts in nude mice (Tai et al. Mol Ther. 2005;12:842) and lead to increased survival in treatment groups compared to controls. In preparation for clinical trials we have improved the CD gene activity and further stabilized the vector structure to create Toca 511. We investigated the functionality of Toca 511 using stereotactic, intratumoral delivery in a syngeneic, orthotopic glioma model in immune-competent B6C3F1 mice. Freshly excised tumors were analyzed by quantitative PCR, Western, and HPLC. Results: Brain tumors isolated from mice treated with Toca 511 and fluorocytosine (5FC) had observable expression of CD protein and vector copy numbers per genome that demonstrate efficient tumor infection. Extensive tumor specific viral spread with almost no spread of vector from the site of injection was observed in the first 24 days. Highly efficient intratumoral conversion of the 5FC prodrug into the anticancer drug 5-fluorouracil (5FU) was demonstrated after intraperitoneal or oral dosing with 5FC. Studies with Toca 511 at high and mid dose levels in combination with 5FC resulted in prolonged survival compared to controls (&amp;gt; 5 months, p&amp;lt;0.0036 and &amp;lt;0.0354 respectively) in this syngeneic glioma model. The highest Toca 511 dose level tested in combination with 5-FC yielded no safety related findings in the mice. Conclusions: Toca 511 efficiently delivers a functional CD gene for expression in glioma cells in a syngeneic, orthotopic model in immune-competent mice. Toca 511 increases survival through the delivery of CD gene and subsequent efficient conversion of 5FC into 5FU within the brain tumor with no safety related findings. A phase 1 ascending dose trial investigating the safety and tolerability of Toca 511 in combination with 5FC in patients with recurrent GBM is about to initiate. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B33.
Obtaining useful data from primary care
Authors: J Robson
Journal: BMJ (1994)

results were obtained for survival up to six months.The analysis was repeated for specific age groups: women aged 60-69 had a worse chance of survival to six months (P<003) but not to two years (P> 0075).No difference was found in either the younger or the older age groups.1.00 40-49 50-59 60-69 o .0cL 0.50 70-79 '.) 0.25 Men Women 0O O 16o 200 300 400 500 600 700 Time after infarction (days)Age specific Kaplan-Meier survival curves in men and women with acute myocardial infarction in first two years after admission to hospital (P>0 44)These Scottish data suggest that the poorer survival of women may be attributed to the different age distributions of the men and women admitted to hospital.The use of statistical methods that adjust for age across whole populations may, however, disguise differences in particular age groups' experience of disease.
Development and construct validation of the angioedema quality of life questionnaire
Authors: K. Weller, A. Groffik, M. Magerl, N. Tohme, P. Martus, K. Krause, M. Metz, P. Staubach, M. Maurer
Journal: Allergy (2012)

Recurrent angioedema is a frequent clinical problem characterized by unpredictably and rapidly occurring cutaneous and mucosal swellings. These swellings may be painful and/or disfiguring. Upper airway involvement can also lead to dyspnea and suffocation. Although the disease burden is high, there is currently no specific instrument to measure health-related quality of life (QoL) impairment.To develop and validate the first symptom-specific tool to assess QoL impairment in recurrent angioedema patients, adhering to established methodological recommendations.During the development phase, 29 questions (items) were generated. Subsequently, item reduction was performed by means of impact analysis and factor analysis as well as by checking for content and face validity. As a result, 17 items were selected and included in the final instrument, the Angioedema QoL Questionnaire (AE-QoL). AE-QoL was then tested for its validity, reliability, and influence factors.One hundred and ten angioedema patients took part in the validation of AE-QoL. AE-QoL was found to have a four-dimensional structure as well as a valid total score. All of its four domains (functioning, fatigue/mood, fears/shame, food) showed good levels of internal consistency with Cronbach's alpha > 0.8. Test-retesting revealed a good reliability of the instruments total score and domain scores. Gender as well as the patients' self-rated disease activity was found to be predictors of the AE-QoL total score.Angioedema Quality of Life Questionnaire is the first angioedema-specific QoL questionnaire. It is a short, valid and reliable instrument that may serve as a valuable tool in future clinical studies and in routine patient care.
The Y-chromosome point mutation rate in humans
Authors: Agnar Helgason, Axel W Einarsson, Valdís B Guðmundsdóttir, Ásgeir Sigurðsson, Ellen D Gunnarsdóttir, Anuradha Jagadeesan, S Sunna Ebenesersdóttir, Augustine Kong, Kári Stefánsson
Journal: Nature Genetics (2015)