tbuckley/cabot-search huggingface dataset:
Abstract 5474: The formin, DIAPH3, regulates response to MT stabilizing drugs in prostate and breast cancer
Authors: Samantha Morley, Sara G. Pollan, Sungyong You, Beatrice S. Knudsen, Michael Freeman
Journal: Cancer Research (2014)

Abstract Diaphanous-related formin-3 (DIAPH3), a cytoskeletal regulator of the formin family, is lost at high frequency in metastatic breast and prostate cancers and has characteristics of a non-canonical metastasis suppressor. We previously showed that DIAPH3 silencing evokes a transition to an “amoeboid” phenotype, characterized by rapid motility, RhoA/ROCK and ERK pathway activation, dynamic membrane blebbing and increased shedding of microvesicles. Here we demonstrate that DIAPH3 loss reduces microtubule (MT) stability in prostate and breast cancer cell lines, and increases the cells' sensitivity to the taxanes, paclitaxel and docetaxel and the non-taxane, epothilone B. DIAPH3 silencing reduces membrane localization of the multidrug resistance-associated protein, MRP1, a regulator of taxane efflux, and increases intracellular accumulation of fluorescent paclitaxel. Baseline acetylation of tubulin, which is proportional to the number of stable MT, is lower in DIAPH3-silenced cells. In contrast, the fold-increase of tubulin acetylation after treatment with MT stabilizing drugs is greater in DIAPH3 knockdown compared to control cells. Further, cytotoxicity induced by paclitaxel, docetaxel or epothilone B is enhanced by DIAPH3 silencing. Analysis of gene expression profiles of breast cancer patients treated with chemotherapeutic regimens containing taxanes in a neoadjuvant phase-2 clinical trial revealed that low DIAPH3 expression is associated with increased relapse free survival. Collectively, the data demonstrate that DIAPH3 deficiency increases responsiveness to widely used MT stabilizing drugs. These findings have implications for the inclusion of DIAPH3 in biomarker panels that stratify patients for treatment with taxanes, in particular in the neoadjuvant setting. Citation Format: Samantha Morley, Sara G. Pollan, Sungyong You, Beatrice S. Knudsen, Michael Freeman. The formin, DIAPH3, regulates response to MT stabilizing drugs in prostate and breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5474. doi:10.1158/1538-7445.AM2014-5474
Acquired Right Bundle-Branch Block and Left Anterior Hemiblock in Ostium Primum Atrial Septal Defect
Authors: DWAIN L. ECKBERG, JOHN ROSS, JACOB R. MORGAN
Journal: Circulation (1972)

Over a 3-year period of observation, the electrocardiogram in an adult patient with an ostium primum atrial septal defect changed from first-degree atrioventricular block alone to right bundle-branch block and left-axis deviation (left anterior hemiblock) with variable atrioventricular block. Coronary atherosclerosis was excluded by selective coronary arteriography. Although right bundle-branch block and left anterior hemiblock are commonly present at birth in patients with endocardial cushion defect, this is believed to represent the first reported instance in which these electrocardiographic abnormalities have developed under observation in later life. It is postulated that chronic hemodynamic stress contributed to the progression of disease in the conduction system.
Spectrofluorescent detection of in vivo red cell lipid peroxidation in patients treated with diaminodiphenylsulfone.
Authors: B D Goldstein, E M McDonagh
Journal: Journal of Clinical Investigation (1976)

In the absence of vitamin E deficiency, red cell lipid peroxidation has not been clearly demonstrated in freshly drawn blood obtained from patients with various hemolytic anemias despite indirect evidence that oxidative decomposition of cell membrane unsaturated fatty acids occurs in these particular hemolytic states. Recent studies have indicated that malonaldehyde, a decomposition product of oxidized polyunsaturated fatty acids, is able to covalently cross-link the amino groups of protein or lipid resulting in a fluorescent compound. In the present study we have utilized spectrofluorescent technique to assess whether such fluorescence is present in red cell lipid extracts in association with lipid peroxidation. In vitro red cell lipid peroxidation produced by ultraviolet radiation or the oxidant gas ozone was associated with the development of a fluorescent peak (excitation maximum 360 nm; emission maximum 440 nm) in lipid-containing red cell extracts Similar fluorescence was observed after incubation of red cells with malonaldehyde or with malonaldehyde-containing extracts of peroxidized red cell lipid. Spectrofluorescent evaluation of chloroform: isopropanol extracts obtained from the freshly drawn red cells of six patients receiving the oxidant hemolytic drug diaminodiphenylsulfone also revealed a peak at 440 nm which ranged from 39 to 78 U. In contrast, the levels in samples obtained from 11 hematologically normal subjects were 17-27 fluorescence U. No evidence for an increase in blood levels of free malomaldehyde was observed using the 2-thiobarbituric acid test which is the most commonly performed assay of lipid peroxidation. Serum vitamin E levels were within the normal range. Density separation indicated that the bulk of the fluorescence was present in older red cells. A similar fluorescent peak was also observed in lipid-containing extracts of red cells obtained from rabbits repeatedly injected with phenylhydrazine. The finding of fluorescent spectra consistent with the cross-linking of aminolid by malonaldehyde in the red cells of patients receiving diaminodiphenylsulfone indicates that in vivo red cell lipid peroxidation does occur in the absence of vitamin E deficiency.
Does this work for you?
Authors: N. A Christakis
Journal: BMJ (2008)

<h3>Objective</h3> Clinical prediction rules (CPRs) followed by D-dimer testing were shown to safely rule out venous thromboembolism (VTE) in about half of all suspected patients in controlled and experienced study settings. Yet, its real-life impact in primary care is unknown. The aim of this study was to determine the real-life impact of CPRs for suspected VTE in primary care. <h3>Design</h3> Cross-sectional cohort study. <h3>Setting</h3> Primary care in the Netherlands. <h3>Participants</h3> Patients with suspected deep venous thrombosis (n=993) and suspected pulmonary embolism (n=484). <h3>Interventions</h3> General practitioners received an educational instruction on how to use CPRs in suspected VTE. We did not rectify incorrect application of the CPR in order to mimic daily clinical care. <h3>Main outcome measures</h3> Primary outcomes were the diagnostic failure rate, defined as the 3-month incidence of VTE in the non-referred group, and the efficiency, defined as the proportion of non-referred patients in the total study population. Secondary outcomes were determinants for and consequences of <i>incorrect</i> application of the CPRs. <h3>Results</h3> In 267 of the included 1477 patients, VTE was confirmed. When CPRs were correctly applied, the failure rate was 1.51% (95% CI 0.77 to 2.86), and the efficiency was 58.1% (95% CI 55.2 to 61.0). However, the CPRs were incorrectly applied in 339 patients, which resulted in an increased failure rate of 3.31% (95% CI 1.07 to 8.76) and a decreased efficiency of 35.7% (95% CI 30.6 to 41.1). The presence of concurrent heart failure increased the likelihood of incorrect application (adjusted OR 3.26; 95% CI 1.47 to 7.21). <h3>Conclusions</h3> Correct application of CPRs for VTE in primary care is associated with an acceptable low failure rate at a high efficiency. Importantly, in nearly a quarter of patients, the CPRs were incorrectly applied that resulted in a higher failure rate and a considerably lower efficiency.
THE M'GRAW LIGATURE.
Authors: A. J. OCHSNER
Journal: JAMA (1905)

More than fifteen years ago, Theodore A. McGraw invented a method of intestinal anastomosis by means of an elastic ligature. As chairman of the Section on Surgery and Anatomy of this Association, he described this method in his address and it was published inThe Journalof the American Medical Association May 16, 1891. The method was tried by its author in a large number of experiments on dogs and twice on human beings before this report was made. He then abandoned the method and employed in its place the Murphy button, which was introduced in 1892. It was not until 1900 that McGraw again brought his method prominently before the medical profession in a paper read before the Mississippi Valley Medical Society<sup>1</sup>at Put-in-Bay. Singularly enough, I listened to the papers at both of these meetings, but did not have the courage to employ this method of anastomosis
EU faces tough decisions after budget cuts
Authors: Rory Watson
Journal: BMJ (2006)

The European Union is facing some tough financial and policy options on its public health policy. After lengthy negotiations, EU governments and the European parliament finally decided on 5 April to allocate some €780m (£542m; $945m) to cover the union's entire public health and consumer protection policies between 2007 and the end of 2013.

This is well below the €1.2bn which the European Commission had originally sought for both policies, and is considerably less than the €969m that it wanted to allocate to health alone.

The institution will have to assess the different projects …
Commercializing University Research
Authors: David Blumenthal, Sherrie Epstein, James Maxwell
Journal: New England Journal of Medicine (1986)

Abstract Universities that are now seeking ways to capture the financial rewards of advances made in biotechnology and other fields on their campuses have been encouraged by the apparent success of previous efforts to benefit from the commercial application of research findings by obtaining patents and granting licenses. Notable among these efforts is the Wisconsin Alumni Research Foundation (WARF). A close examination of the experience of this foundation reveals that, with good fortune and good management, a patenting and licensing organization can enjoy financial success. It also indicates, however, that the success experienced by WARF would be difficult to achieve today and that such efforts may yield lower financial returns than university administrators expect. Universities should be aware that such ventures entail financial risks and pose potential threats to traditional university values. (N Engl J Med 1986; 314: 1621–6.)
Review: Antipsychotic drugs improve symptoms, with different levels of side effects, in schizophrenia
Authors: Adrian Preda
Journal: Annals of Internal Medicine (2013)

Source Citation Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013:382:951-62. 23810019
More evidence shows better outcomes for vascular surgery at high volume hospitals
Authors: Roger Dobson
Journal: BMJ (2007)

Patients with abdominal aortic aneurysms have better chances of survival when they are operated on at hospitals that handle large numbers of cases, a new report shows.

Having elective surgery at hospitals with the greatest volume—those doing more than 32 repairs a year—reduced the odds of mortality by a third compared with the lowest volume centres, say researchers in the British Journal of Surgery (2007 Mar 14, doi: 10.1002/bjs.5725).

“Our research adds to the evidence that concentrating surgical resources in large centres of excellence can provide great benefit to patients. A bad …
Invasive Dental Treatment and Risk for Vascular Events
Authors: Caroline Minassian, Francesco D'Aiuto, Aroon D. Hingorani, Liam Smeeth
Journal: Annals of Internal Medicine (2010)

Background: Treatment of periodontal disease may reduce cardiovascular risk in the longer term, but studies have suggested a link among dental procedures, acute inflammation, and endothelial dysfunction. However, whether such acute inflammatory effects translate into a short-lived increased risk for vascular events is not known. Objective: To investigate whether invasive dental treatment transiently increases the risk for vascular events. Design: Self-controlled case series. Setting: Data came from the U.S. Medicaid claims database. Patients: All persons exposed to invasive dental treatment with a primary hospital discharge diagnosis of ischemic stroke (n = 650) or myocardial infarction (n = 525) from 2002 to 2006. Measurements: The incidence of ischemic stroke and myocardial infarction in periods immediately after invasive dental treatment was compared with the incidence in all other observed time periods. Incidence ratios and 95% CIs were calculated. Results: The rate of vascular events significantly increased in the first 4 weeks after invasive dental treatment (incidence ratio, 1.50 [95% CI, 1.09 to 2.06]) and gradually returned to the baseline rate within 6 months. The positive association remained after exclusion of persons with diabetes, hypertension, or coronary artery disease or persons with prescriptions for antiplatelet or salicylate drugs before treatment. Limitations: Power to examine the effects of invasive dental treatment on stroke and myocardial infarction separately was limited because of the low frequency of invasive dental procedures. Lack of information about use of over-the-counter drugs limited the ability to assess confounding by possible withholding of antiplatelet or salicylate drugs before invasive dental treatment or by the use of nonsteroidal anti-inflammatory drugs after treatment. Conclusion: Invasive dental treatment may be associated with a transient increase in the risk for vascular events. However, the absolute risks are minimal, and the long-term benefits on vascular health will probably outweigh the short-lived adverse effects. Primary Funding Source: Wellcome Trust.
Getting serious about obesity
Authors: D. Stuckler, S. Basu
Journal: BMJ (2013)

Reports from UK medical bodies are a start, but doctors can’t do it alone

Obesity continues to be one of the biggest health threats to the UK population. We therefore welcome the fact that two of the United Kingdom’s most important medical organisations—the Royal College of Physicians (RCP) and the Academy of Medical Royal Colleges—have launched major reports this year setting out concrete steps for responding to this crisis.

According to the BMA’s consensus statement on the role of the doctor,1 doctors have to act in “the best interests of their patients and of the population served.” In helping serve the best interests of patients, the RCP report takes several important steps to help bring UK clinical practices in line with those in the United States, which also has an obesity crisis.2 These include developing bariatric medicine as a clinical subspecialty, along with better education for general practitioners, a patient charter, introducing a cross governmental obesity chief, and research into better pharmaceutical and surgical interventions to treat obesity as a medical condition.

Yet such actions can play only a small part in tackling the UK’s obesity crisis. Thirty years ago the RCP …
New and old thoughts on migraine.
Authors: J N Blau
Journal: BMJ (1985)

potential risk to the infant: the prolonged interruption of feeding advocated for some agents is often impracticable.34 37Interruption for 24 hours (as recommended by some authors) for 9mTc compounds is excessive for doses used in Britain.Twelve hours leaves a wide range of safety for pertechnetate.No interruption is needed for 9smTc-macroaggregated albumin and 9mTc-diethylenetriaminepenta-acetic acid in order to remain below one tenth of the annual limit of intake-but in practice mothers are often reassured by a short interruption.39When an investigation is needed for which no data on breast milk secretion are available the mother should be advised to stop breast feeding until measurements made on the expressed milk show it safe to resume.The list of problems is long, but in practice the risk to the infant is small from most radiopharmaceuticals now in use.Simple precautions will allow most investigations to be performed with little inconvenience.The recommended precautions must err on the side of safety, but as more information becomes available such advice should be able to become less restrictive, particularly with regard to interruption of breast feeding.
Severe Insulin-Induced Lipohypertrophy Successfully Treated by Liposuction
Authors: Kevin J Hardy, Geoffrey V Gill, J Richard Bryson
Journal: Diabetes Care (1993)

OBJECTIVE— To examine the usefulness of liposuction surgery on diabetic patients with lipohypertrophy. RESEARCH DESIGN AND METHODS— We treated a diabetic patient who suffered from severe localized thigh lipohypertrophy. When she did not respond to conventional treatment of resting the injection site, we recommended liposuction surgery. RESULTS— Our patient's lipohypertrophy was immediately cured by the liposuction procedure. CONCLUSIONS— Liposuction surgery could be useful in patients with diabetic lipohypertrophy who do not respond to more conservative treatments.
Staff in the drug industry want “to help people,” academic says
Authors: Lynn Eaton
Journal: BMJ (2004)

Richard Sykes, rector of Imperial College, London, and former chairman of GlaxoSmithKlein, gave a robust defence of people working in the pharmaceutical industry when he appeared before the Commons health committee last week.

“People go to work in the pharmaceutical industry because they have a mission. These are not people driven by greed or avarice, they are driven by a desire to be successful, to do something to help people,” he told the committee's …
Superannuation and the Elderly G.P
Authors: G. D. J. Ball, C. R. Barker, T. L. Chester-Williams
Journal: BMJ (1973)

relevant to the choice of treatment and might explain why the pseudomonas in the sputum of one patient "showed no sign of suppression by colistin aerosol."Also, many pseudomonas (60%) are sensitive to tetra- cydline and this might explain the finding that tetracycline is "less likely to be interfered with by pseudomonas" in the treatment of underlying infection.I would question the presumption that pseudomonas can reach the pharynx by ascending the oesophagus.Though I have cultured many different organisms from the small intestine, I have never found pseudomonas as high as the duodenum in the gastrointestinal tract.There are many other more likely sources of infection, as pseudomonas conmnonly contaminates hospital equipment (especially ventilators, humidifiers, and suction apparatus), contaminates hos- pital food,' and is carried on the hands of staff, contaminated by an infected patient.-I
GMC consults doctors on prescribing cheap unlicensed drugs to save money
Authors: C. Dyer
Journal: BMJ (2011)

Doctors may prescribe a cheaper unlicensed or off-label alternative to a licensed medicine, as long as it is approved in authoritative clinical guidelines and is just as safe and effective as the licensed version, the General Medical Council is to propose for the first time in new guidance on prescribing for UK doctors.

New standards for those working in sports medicine are also set out, requiring doctors to report their suspicions that an athlete’s performance has been improperly enhanced if it is in the public interest.

The draft guidance, which is open for consultation until 27 …
D6-06: Detection of circulating tumour cells from peripheral blood samples by a novel cell concentration method and immunohistochemistry (IHC) compared with reverse transcriptase-polymerase chain reaction (RT-PCR) in Stage III/IV Non-small cell lung cancer (NSCLC)
Authors: Caroline Chung, Bryan Knight, Carrie Peters, Chad Malloff, Wan Lam, Finbarr Sheehan
Journal: Journal of Thoracic Oncology (2007)
Self-Monitoring of Blood Glucose in Noninsulin-Using Type 2 Diabetic Patients
Authors: Uriëll L. Malanda, Sandra D. Bot, G. Nijpels
Journal: Diabetes Care (2012)

Given the importance of glycemic control in the development of diabetes complications, the plethora of tools now available to monitor the day-to-day trends in glycemia is remarkable. In this regard, self-monitoring of blood glucose (SMBG) has been considered a key component of patient management. Arguably, there remains almost universal agreement that SMBG should be available to all diabetic patients regardless of current treatment strategy. However, recently there have been reports that have challenged the current paradigm that all patients should use SMBG and concluded that SMBG for type 2 diabetic patients not on insulin may not be beneficial on glycemic control and must be weighed against the expense and inconvenience. In this two-part point-counterpoint narrative, Malanda et al. and Polonsky and Fisher take opposing views on the utility of SMBG to be valuable for individuals with type 2 diabetes not using insulin. In the narrative below, Malanda et al. suggest that the evidence for potentially beneficial SMBG-induced effects on glycemic control, hypoglycemic periods, and potential harms in type 2 diabetic patients who are not treated with insulin does not justify the use of SMBG. Moreover, the use of SMBG is associated with huge costs, which should be better redirected to effective strategies to improve health for this category of patients. -William T. Cefalu, MD Editor in Chief, Diabetes Care.
HLA-DR expression by labial minor salivary gland tissues in Sjogren's syndrome.
Authors: H M Moutsopoulos, J J Hooks, C C Chan, Y A Dalavanga, F N Skopouli, B Detrick
Journal: Annals of the Rheumatic Diseases (1986)

Minor salivary gland biopsy specimens from patients with Sjögren's syndrome (primary and secondary) and from normal controls were examined with the four step biotin-avidin-immunoperoxidase assay. The composition of the infiltrating cells was similar in patients with both primary and secondary Sjögren's syndrome, consisting primarily of T lymphocytes with predominance of T helper/inducer cells. B lymphocytes (Leu-14) were approximately 20-35% of the infiltrating lymphocytes, while only a few OKM1 (monocytes/macrophages) cells and Leu-7+ (natural killer; NK) cells were observed. The majority of infiltrating lymphocytes expressed HLA-DR antigens. In the biopsy specimens of the controls there were no infiltrates; the scattered lymphocytes, however, were also predominantly T lymphocytes. Finally, the glandular epithelial cells (ducts and acini) were inappropriately expressing HLA-DR antigens, in contrast with controls where minimal HLA-DR expression was found.
Sajal Kumar Ghosh
Authors: Gerhard Behr
Journal: BMJ (2005)

Former consultant radiologist Burnley (b Calcutta 1933; q Calcutta 1956; DMRD), d 26 August 2005.

Sajal came to England to train in orthopaedic surgery and became registrar in orthopaedic surgery at Walton Hospital in Liverpool. But paralysed on the left side by a cerebral embolus following surgery for a heart condition, he could not go on with his ambition to become an orthopaedic surgeon, and instead trained in radiology. In 1969 he was appointed consultant radiologist in Burnley, where a new x ray department was in the planning stage. Kumar revised the plans and the new department was built fulfilling all his predictions. In 1984 his heart condition needed further surgery, but he was able to carry on with his work and retired in 1998. He leaves a wife, Katie, and a son.