tbuckley/cabot-search huggingface dataset:
Abstract 854: Alternative dosing regimens with the EGFr inhibitors (Gefitinib and Lapatinib) in a mammary cancer model: Prevention efficacy
Authors: Ronald A. Lubet, Ann Bode, Eva Szabo, Clinton J. Grubbs
Journal: Cancer Research (2011)

Abstract The EGFR inhibitors (Gefitinib, Lapatinib) have proven to be effective in preventing cancers in multiple animal models, including ER and Neu positive breast, head and neck, and urinary bladder cancers when administered daily. However, the development of toxicities (Iressa, skin rashes; Lapatinib, diarrhea) limit their potential use in prevention; and perhaps even in an adjuvant setting. We, therefore, tested whether alternative dosing regimens (which might reduce toxicity) would still achieve preventive and therapeutic efficacy. Female Sprague-Dawley rats were administered a single IV dose of methylnitrosourea (MNU) at 50 days of age. In the prevention study, rats were administered Gefitinib by gavage beginning five days after MNU. MNU treated rats were administered Gefitinib daily (10 mg/kg BW/day, 7x/week) or Gefitinib (70 mg/kg BW, 1x/week). These treatment regimens resulted in 94 and 75% reductions in tumor multiplicity, respectively. Simultaneous measurements of tumor load (number of tumors x tumor weight) showed that both regimens resulted in greater than a 90% decrease. In the therapeutic study (initiating treatment when animals developed a small palpable tumor), both regimens were highly effective. A similar prevention study was performed with Lapatinib (75 mg/kg BW/day, 7x/week or 525 mg/kg BW, 1x/week). While the daily dose reduced cancer multiplicity 90%, the weekly dose caused a 70% reduction. These data show that even a great alteration of the dosing of Gefitinib (EGFR1) or Lapatinib (EGFR 2/1) resulted in a large reduction in mammary cancers. The significant clinical question will be whether this altered dosing will diminish the toxicities associated with these agents. We cannot determine this in the animal model since, at the effective doses employed, the typical toxicities observed in humans were not observed. Supported by NCI contract number HHSN261200433001C. 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 854. doi:10.1158/1538-7445.AM2011-854
Estimation of blood-flow quality by statistical analysis or an ultrasonic Doppler signal: application to the study of perturbations caused by a vascular stenosis
Authors: J.-P. MOUTET, A. HERMENT, J.-P. GUGLIELMI, M. PIECHOCKI, P. PERONNEAU
Journal: Cardiovascular Research (1983)

The noninvasive detection of pathological stenoses by Doppler ultrasound velocimetry is based on the appearance of modifications in velocity waveform or of a local increase in velocity. Nevertheless, these methods suffer from a lack of sensitivity. An extension of ultrasonic velocimetry including a statistical treatment of the Doppler signals affords a quantitative approach to the flow quality and seems to be able to improve the diagnosis of vascular obliterans. Accordingly a perturbation index can be computed on a microprocessor as the relative standard deviation of the zero-crossings histogram of the Doppler signal. A theoretical and experimental approach has been attempted to validate this method. Moreover, this index has been tested in vitro on calibrated flows. The in vivo experiments, performed on the abdominal aorta of the dog with artificial stenoses (0 to 50% in diameter) show a significant increase in the index value downstream from the stenosis. The relative increase of the index is greater than that of velocities for the same degree of obstruction. At the moment, it is possible to detect stenoses of 20% and above. It should be noted that changes in the perturbation index can be observed on a large part of the arterial segment, in relation with the severity of the stenosis. Taking into account the increase in the index value and the length of the disturbed zone downstream of the stenosis, an estimation of the severity itself can be attempted. Clinical applications are in progress pointing out the diagnostic and prognostic abilities of the index method. The index perturbation method adds to velocity measurement the possibility of blood flow stability estimation. It appears useful for the localisation of stenoses, offers the possibility of quantifying their severity and could help the prognosis of their development.
Pulmonary embolism in hospital practice: Certain crucial procedures were omitted
Authors: Adrian J B Brady
Journal: BMJ (2006)

EDITOR—Robinson says that diagnosis of pulmonary embolism can be difficult but does not mention the available scoring systems that are useful in defining the likelihood of pulmonary thromboembolism.1 2 Most importantly, she makes no mention of biomarkers and does not emphasise the critical importance of echocardiography or …
IS THERE MERIT IN THE SO-CALLED "CEREBRAL PALSY" PROGRAM?-Reply
Authors: M. A. Perlstein
Journal: JAMA (1949)

To the Editor:—  Some of the arguments set forth by Dr. McCarroll are logical, but would have more merit if his premises were as correct as his thinking. He states, for example,  some instances writers imply that a program of muscle training and reeducation will afford continuous improvement in muscle control and function and will eliminate need for surgery to correct deformities even in selected cases. What can be expected of a program of this type? The implication is, of course, that this quotation expresses the opinion of those who are most interested in furthering the so-called cerebral palsy program. In actuality, however, nothing could be further from the truth.  Any program which limits itself to muscle training and reeducation or to surgical correction and ignores socialization, speech correction, education, occupational therapy and the correction of sensory, emotional and other defects is incomplete. Despite Dr. McCarroll's statement as quoted here, I do not
GPs are to refer suspected cancer patients for tests in a week under new scheme
Authors: O. Ellis
Journal: BMJ (2009)

Prime Minister Gordon Brown is expected to announce that by 2014 all patients with suspected cancer will undergo key diagnostic tests within one week.

A report in the Guardian newspaper said that up to 10 000 lives a year could be saved by the new initiative, which will see GPs being given the authority to directly refer patients to diagnostic services (www.guardian.co.uk, 26 Sep, “Gordon Brown to woo conference with cancer pledge and new NHS cash”). 

Mr Brown’s speech was not released before he delivered it to the Labour party conference on Tuesday afternoon, as the BMJ went to press.

New imaging equipment is expected to be purchased, with funding coming from …
Effects of Intravenous and Intracoronary Adenosine 5′-Triphosphate as Compared With Adenosine on Coronary Flow and Pressure Dynamics
Authors: Allen Jeremias, Steven D. Filardo, Robert J. Whitbourn, Robert S. Kernoff, Alan C. Yeung, Peter J. Fitzgerald, Paul G. Yock
Journal: Circulation (2000)

Background —Measurements of Doppler derived coronary flow reserve (CFR) and pressure derived fractional flow reserve (FFR) for coronary stenosis assessment depend on the induction of maximal hyperemia. Adenosine is the most widely used pharmacological agent but is expensive and poorly tolerated by some patients. Methods and Results —The objective of this study was to test the equivalency of adenosine 5′-triphosphate (ATP) to adenosine in their ability to cause maximal hyperemia as compared with the hyperemic response of complete coronary occlusion in 6 canines. Intracoronary administration of either ATP or adenosine resulted in a significant increase in CFR (2.79±0.64 and 2.22±0.7 for 10 μg versus 4.65±1.22 and 4.25±0.78 for 100 μg for ATP and adenosine, respectively, P for trend &lt;0.001) but not reaching the level of coronary occlusion (6.35±2.26). Additionally, FFR and CFR were measured in 35 different stenoses using ATP, adenosine, and coronary occlusion. There was an excellent linear correlation between ATP and adenosine for both CFR ( R =0.934, P &lt;0.001) and FFR ( R =0.985, P &lt;0.001). However, hyperemia with either ATP or adenosine was less than postocclusion hyperemia, resulting in significantly different reserve measurements (CFR: 1.93±0.66 and 2.08±0.81 versus 2.35±0.97, P &lt;0.001; FFR: 0.62±0.24 and 0.63±0.23 versus 0.58±0.2, P &lt;0.001). Conclusions —1) Step up in dosage of ATP and adenosine beyond currently recommended clinical doses resulted in a significant increase in coronary hyperemia; 2) ATP was equivalent to adenosine for both CFR and FFR; and 3) complete coronary occlusion yielded a better hyperemic response than either drug, indicating that maximal hyperemia was not achieved by either pharmacological stimulus.
I was misquoted over very premature babies
Authors: D. Austin
Journal: BMJ (2011)

Months ago I agreed to take part in a television documentary that the UK film maker Adam Wishart was making about premature babies. He was keen to have a commissioner’s input, although he got a public health doctor’s view—which is not quite the same thing. Adam and I met on a couple of occasions over a period of weeks, and at the third meeting he interviewed me for more than an hour. At this time the documentary was a work in progress, so I didn’t know where and how I would fit in. The final product was 23 Week Babies: The Price of Life , recently shown on BBC Two.

Before the documentary was released I was informed of its content, the arguments, and my contribution. Although I was not entirely sure that my views would be fully conveyed, I was satisfied, given the specific issues that Adam wished to consider, that my input complemented the views of others.

Media interest was generated before the documentary was aired, with The Big Questions (BBC One), Woman’s Hour (BBC Radio 4), Victoria Derbyshire (BBC Radio 5 Live), Jeremy Vine (BBC Radio 2), and BBC Radio Scotland wanting to cover the subject. My first outing was on The Big Questions . I was introduced as “the doctor who thought babies born at 23 weeks should be left to die.” That’s …
South African health minister sacked after attending AIDS conference
Authors: Pat Sidley
Journal: BMJ (2007)

President Thabo Mbeki of South Africa last week fired his outspoken deputy minister of health, Nozizwe Madlala-Routledge. The sacking unleashed an unusually vigorous wave of support for her among opposition parties, trade unions, doctors, and AIDS activists as well as a torrent of criticism against the minister of health, Manto Tshabalala-Msimang, and the president.

Ms Madlala-Routledge had flown to an AIDS conference in Madrid in June, which Mr Mbeki says she did not have permission to attend. She told a radio station after being sacked that she had been invited to address the International AIDS Vaccine Initiative (IAVI) meeting and believed she had permission to go before leaving. When told she …
China's excess males, sex selective abortion, and one child policy: analysis of data from 2005 national intercensus survey
Authors: W. X. Zhu, L. Lu, T. Hesketh
Journal: BMJ (2009)

<b>Objectives</b> To elucidate current trends and geographical patterns in the sex ratio at birth and in the population aged under 20 in China and to determine the roles played by sex selective abortion and the one child policy. <b>Design</b> Analysis of household based cross sectional population survey done in November 2005. <b>Setting</b> All of China’s 2861 counties. <b>Population</b> 1% of the total population, selected to be broadly representative of the total. <b>Main outcome measure</b> Sex ratio defined as males per 100 females. <b>Results</b> 4 764 512 people under the age of 20 were included. Overall sex ratios were high across all age groups and residency types, but they were highest in the 1-4 years age group, peaking at 126 (95% confidence interval 125 to 126) in rural areas. Six provinces had sex ratios of over 130 in the 1-4 age group. The sex ratio at birth was close to normal for first order births but rose steeply for second order births, especially in rural areas, where it reached 146 (143 to 149). Nine provinces had ratios of over 160 for second order births. The highest sex ratios were seen in provinces that allow rural inhabitants a second child if the first is a girl. Sex selective abortion accounts for almost all the excess males. One particular variant of the one child policy, which allows a second child if the first is a girl, leads to the highest sex ratios. <b>Conclusions</b> In 2005 males under the age of 20 exceeded females by more than 32 million in China, and more than 1.1 million excess births of boys occurred. China will see very high and steadily worsening sex ratios in the reproductive age group over the next two decades. Enforcing the existing ban on sex selective abortion could lead to normalisation of the ratios.
Langerhans cells are critical in epicutaneous sensitization with protein antigen via thymic stromal lymphopoietin receptor signaling
Authors: Saeko Nakajima, Botond Z. Igyártó, Tetsuya Honda, Gyohei Egawa, Atsushi Otsuka, Mariko Hara-Chikuma, Norihiko Watanabe, Steven F. Ziegler, Michio Tomura, Kayo Inaba, Yoshiki Miyachi, Daniel H. Kaplan, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2012)
Isolated perfused lung preparation for studying altered gaseous environments.
Authors: R A Rhoades
Journal: Environmental Health Perspectives (1984)

The isolated perfused lung (IPL) preparation is ideally suited to investigate lung dynamics and cellular function, and is easily adapted to investigating biochemical and physiological responses to environmental insults. The IPL offers several advantages which permit one to study endothelial/epithelial interactions that are often disrupted with other model systems (e.g., isolated cells, minces, slices, homogenates, etc.). The IPL developed in our laboratory was devised for the rat lung and allows four lungs to be perfused simultaneously in which control over ventilation, flow, pressure, pH, PO2 and PCO2 can be maintained. Isolated lungs perfused for 1 to 2 hr at a flow rate of 10 mL/min exhibit less that 2% weight gain, maintain normal ATP levels, and exhibit linear substrate uptake. Mechanisms leading to changes in vascular and airway resistance, lipid metabolism, vasoactive hormones, blood gases and changes in vascular permeability mediated by environmental insults can be quantified in the IPL preparation.
Association between chlorination of drinking water and adverse pregnancy outcome in Taiwan.
Authors: C Y Yang, B H Cheng, S S Tsai, T N Wu, M C Lin, K C Lin
Journal: Environmental Health Perspectives (2000)

Chlorination has been the major means of disinfecting drinking water in Taiwan. The use of chlorinated water has been hypothesized to lead to several adverse birth outcomes, including low birth weight and preterm delivery. We performed a study to examine the relationship between the use of chlorinated water and adverse birth outcomes in Taiwan. The study areas included 14 chlorinating municipalities (CHMs), which were defined as municipalities in which > 90% of the municipal population was served by chlorinated water, and 14 matched nonchlorinating municipalities (NCHMs), defined as municipalities in which < 5% of the municipal population is served by chlorinated water. The CHMs and NCHMs were similar to one another in terms of level of urbanization and sociodemographic characteristics. The study population comprised 18,025 women residing in the 28 municipalities who had a first parity singleton birth between 1 January 1994 and 31 December 1996 and for which complete information on maternal age, education, gestational age, birth weight, and sex of the baby were available. The results of our study suggest that there was no association between consumption of chlorinated drinking water and the risk of low birth weight.
Antimyeloperoxidase antibodies rapidly induce α4-integrin–dependent glomerular neutrophil adhesion
Authors: Michael P. Kuligowski, Rain Y. Q. Kwan, Cecilia Lo, Cyndi Wong, Will G. James, Dorothee Bourges, Joshua D. Ooi, Latasha D. Abeynaike, Pam Hall, A. Richard Kitching, Michael J. Hickey
Journal: Blood (2009)
FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia
Authors: Z Pašaliç, P A Greif, V Jurinoviç, M Mulaw, P M Kakadia, B Tizazu, L Fröhlich-Archangelo, A Krause, S K Bohlander
Journal: Blood Cancer Journal (2011)

The t(10;11)(p13;q14) translocation results in the fusion of the CALM (clathrin assembly lymphoid myeloid leukemia protein) and AF10 genes. This translocation is observed in acute myeloblastic leukemia (AML M6), acute lymphoblastic leukemia (ALL) and malignant lymphoma. Using a yeast two-hybrid screen, the four and a half LIM domain protein 2 (FHL2) was identified as a CALM interacting protein. Recently, high expression of FHL2 in breast, gastric, colon, lung as well as in prostate cancer was shown to be associated with an adverse prognosis. The interaction between CALM and FHL2 was confirmed by glutathione S-transferase-pulldown assay and co-immunoprecipitation experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294-335 of CALM. The transcriptional activation capacity of FHL2 was reduced by CALM, but not by CALM/AF10, which suggests that regulation of FHL2 by CALM might be disturbed in CALM/AF10-positive leukemia. Extremely high expression of FHL2 was seen in acute erythroid leukemia (AML M6). FHL2 was also highly expressed in chronic myeloid leukemia and in AML with complex aberrant karyotype. These results suggest that FHL2 may play an important role in leukemogenesis, especially in the case of AML M6.
Anti-BR3 antibodies: a new class of B-cell immunotherapy combining cellular depletion and survival blockade
Authors: Wei Yu Lin, Qian Gong, Dhaya Seshasayee, Zhonghua Lin, Qinglin Ou, Shiming Ye, Eric Suto, Jean Shu, Wyne Pun Lee, Ching-Wei V. Lee, Germaine Fuh, Maya Leabman, Suhasini Iyer, Kathy Howell, Thomas Gelzleichter, Joseph Beyer, Dimitry Danilenko, Sherry Yeh, Laura E. DeForge, Allen Ebens, Jeffrey S. Thompson, Christine Ambrose, Mercedesz Balazs, Melissa A. Starovasnik, Flavius Martin
Journal: Blood (2007)
A novel tool to analyze MRI recurrence patterns in glioblastoma
Authors: Wolfgang Wick, Roger Stupp, Anna-Carina Beule, Jacoline Bromberg, Antje Wick, Ulrike Ernemann, Michael Platten, Christine Marosi, Warren P. Mason, Martin van den Bent, Michael Weller, Chris Rorden, Hans-Otto Karnath
Journal: Neuro-Oncology (2008)

At least 10% of glioblastoma relapses occur at distant and even contralateral locations. This disseminated growth limits surgical intervention and contributes to neurological morbidity. Preclinical data pointed toward a role for temozolomide (TMZ) in reducing radiotherapy-induced glioma cell invasiveness. Our objective was to develop and validate a new analysis tool of MRI data to examine the clinical recurrence pattern of glioblastomas. MRIcro software was used to map the location and extent of initial preoperative and recurrent tumors on MRI of 63 patients in the European Organisation for Research and Treatment of Cancer (EORTC) 26981/22981/National Cancer Institute of Canada (NCIC) CE.3 study into the same stereotaxic space. This allowed us to examine changes of site and distance between the initial and the recurrent tumor on the group level. Thirty of the 63 patients were treated using radiotherapy, while the other patients completed a radiotherapy-plus-TMZ treatment. Baseline characteristics (median age, KPS) and outcome data (progression-free survival, overall survival) of the patients included in this analysis resemble those of the general study cohort. The patient groups did not differ in the promoter methylation status of methyl guanine methyltransferase (MGMT). Overall frequency of distant recurrences was 20%. Analysis of recurrence patterns revealed no difference between the groups in the size of the recurrent tumor or in the differential effect on the distance of the recurrences from the preoperative tumor location. The data show the feasibility of groupwise recurrence pattern analysis. An effect of TMZ treatment on the recurrence pattern in the EORTC 26981/22981/NCIC CE.3 study could not be demonstrated.
Medical housing "lines"
Authors: H. S Kohli
Journal: BMJ (1986)

General practitioners are often asked for medical certificates (housing "lines") by applicants for council housing who claim to have medical problems requiring housing priority. The results of a survey by questionnaire showed that general practitioners in Edinburgh do not know how the housing system works and that they seem to overestimate their patients' chances of obtaining suitable council housing. General practitioners need to know how the housing system works, and communication between general practitioners and housing departments should be improved. A comparison was also made between the number of medical points awarded by a community medicine specialist and a group of general practitioners who had written housing "lines" for their patients. The general practitioners tended to award more points than the specialist. Social priority for housing should be recognised as an independent factor and a new category of top social priority added.
Potentiation of High-LET Radiation by Gemcitabine: Targeting HER2 with Trastuzumab to Treat Disseminated Peritoneal Disease
Authors: Diane E. Milenic, Kayhan Garmestani, Erik D. Brady, Paul S. Albert, Alia Abdulla, Joseph Flynn, Martin W. Brechbiel
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Recent studies from this laboratory with 212Pb-trastuzumab have shown the feasibility of targeted therapy for the treatment of disseminated peritoneal disease using 212Pb as an in vivo generator of 212Bi. The objective of the studies presented here was improvement of the efficacy of α-particle radioimmunotherapy using a chemotherapeutic agent. Experimental Design: In a series of experiments, a treatment regimen was systematically developed in which athymic mice bearing i.p. LS-174T xenografts were injected i.p. with gemcitabine at 50 mg/kg followed by 212Pb radioimmunotherapy. Results: In a pilot study, tumor-bearing mice were treated with gemcitabine and, 24 to 30 h later, with 5 or 10 μCi 212Pb-trastuzumab. Improvement in median survival was observed at 5 μCi 212Pb-trastuzumab in the absence (31 days) or presence (51 days) of gemcitabine: 45 and 70 days with 10 μCi versus 16 days for untreated mice (P &amp;lt; 0.001). Multiple doses of gemcitabine combined with a single 212Pb radioimmunotherapy (10 μCi) administration was then evaluated. Mice received three doses of gemcitabine: one before 212Pb-trastuzumab and two afterwards. Median survival of mice was 63 versus 54 days for those receiving a single gemcitabine dose before radioimmunotherapy (P &amp;lt; 0.001), specifically attributable to 212Pb-trastuzumab (P = 0.01). Extending these findings, one versus two treatment cycles was compared. A cycle consisted of sequential treatment with gemcitabine, 10 μCi 212Pb radioimmunotherapy, then one or two additional gemcitabine doses. In the first cycle, three doses of gemcitabine resulted in a median survival of 90 versus 21 days for the untreated mice. The greatest benefit was noted after cycle 2 in the mice receiving 10 μCi 212Pb-trastuzumab and two doses of gemcitabine with a median survival of 196.5 days (P = 0.005). Pretreatment of tumor-bearing mice with two doses of gemcitabine before 212Pb radioimmunotherapy was also assessed with gemcitabine injected 72 and 24 h before 212Pb-trastuzumab. The median survival was 56 and 76 days with one and two doses of gemcitabine versus 49 days without gemcitabine. The effect may not be wholly specific to trastuzumab because 212Pb-HuIgG with two doses of gemcitabine resulted in a median survival of 66 days (34 days without gemcitabine). Conclusions: Treatment regimens combining chemotherapeutics with high-LET targeted therapy may have tremendous potential in the management and care of cancer patients.