tbuckley/cabot-search huggingface dataset:
Ras pathway inhibition prevents neovascularization by repressing endothelial cell sprouting
Authors: Peter D. Westenskow, Toshihide Kurihara, Edith Aguilar, Elizabeth L. Scheppke, Stacey K. Moreno, Carli Wittgrove, Valentina Marchetti, Iacovos P. Michael, Sudarshan Anand, Andras Nagy, David Cheresh, Martin Friedlander
Journal: Journal of Clinical Investigation (2013)

Vascular networks develop from a growing vascular front that responds to VEGF and other guidance cues. Angiogenesis is required for normal tissue function, but, under conditions of stress, inappropriate vascularization can lead to disease. Therefore, inhibition of angiogenic sprouting may prevent neovascularization in patients with blinding neovascular eye diseases, including macular degeneration. VEGF antagonists have therapeutic benefits but also can elicit off-target effects. Here, we found that the Ras pathway, which functions downstream of a wide range of cytokines including VEGF, is active in the growing vascular front of developing and pathological vascular networks. The endogenous Ras inhibitor p120RasGAP was expressed predominately in quiescent VEGF-insensitive endothelial cells and was ectopically downregulated in multiple neovascular models. MicroRNA-132 negatively regulated p120RasGAP expression. Experimental delivery of α-miR-132 to developing mouse eyes disrupted tip cell Ras activity and prevented angiogenic sprouting. This strategy prevented ocular neovascularization in multiple rodent models even more potently than the VEGF antagonist, VEGF-trap. Targeting microRNA-132 as a therapeutic strategy may prove useful for treating multiple neovascular diseases of the eye and for preventing vision loss regardless of the neovascular stimulus.
A comparative study of left ventricular structure and function in elite athletes.
Authors: N MacFarlane, D B Northridge, A R Wright, S Grant, H J Dargie
Journal: British Journal of Sports Medicine (1991)

Adaptations to left ventricular (LV) structure and function appear to be dependent on the type, intensity and duration of exercise training. We therefore studied two clearly defined groups of elite athletes, by M-mode and Doppler echocardiography, with a group of inactive individuals as controls. All groups were age matched. Group 1 comprised ten elite endurance athletes with maximal oxygen consumption (VO2 max) of 74.7 +/- 1.43 (mean +/- SEM). Group 2 consisted of ten elite weightlifters with VO2 max 45.3 +/- 2.00. Group 3 comprised of ten inactive individuals with VO2 max 44.5 +/- 2.13. Left ventricular end diastolic dimension was significantly higher in group 1 (5.72 +/- 0.07) than in groups 2 or 3 (5.29 +/- 0.09 and 5.19 +/- 0.09 respectively, p less than 0.001). Left ventricular mass index was significantly higher in groups 1 and 2 (156.4 +/- 5.97 and 138.6 +/- 7.27 respectively) than in group 3 (104.1 +/- 3.16 p less than 0.001). Percentage fractional shortening was used as an index of systolic function and no significant difference was found between groups. Doppler E:A ratio was taken as an index of diastolic function and was found to be significantly elevated in group 1 at rest (3.37 +/- 0.24) compared with 2.38 +/- 0.16 and 1.99 +/- 0.10 in groups 2 and 3 respectively (p less than 0.003). On exercise, the E:A ratio in group 1 was significantly higher than in group 3 (1.95 +/- 0.14 and 1.23 +/- 0.05 respectively p less than 0.001), and tended to be higher than group 2 (1.68 +/- 0.15 p = ns). These data show that both modes of intense training produce left ventricular hypertrophy. Diastolic function is not impaired in the athletes and may be augmented in the endurance athletes.
Racial and other characteristics of human T cell leukemia/lymphoma (HTLV-I) and AIDS (HTLV-III) in Trinidad.
Authors: C Bartholomew, W Charles, C Saxinger, W Blattner, M Robert-Guroff, C Raju, P Ratan, W Ince, D Quamina, K Basdeo-Maharaj
Journal: BMJ (1985)

Adult T cell leukaemia/lymphoma was first recognised as a clinical entity in southwest Japan. Subsequently the Caribbean has been found to be another area where the disease is endemic, and sporadic cases have been identified in different parts of the world. The human T cell leukaemia/lymphoma virus (HTLV-I) is causally related to adult T cell leukaemia/lymphoma. A subgroup of HTLV, designated HTLV-III, has recently been isolated from many patients with the acquired immunodeficiency syndrome (AIDS) and preAIDS, and there is now evidence that this variant is the primary cause of AIDS. This is the first report from Trinidad to describe 12 cases of adult T cell leukaemia/lymphoma and 14 of AIDS. All were in patients of African descent. No cases were seen in subjects of East Indian descent, who, like those of African descent, comprise as much as 40% of the population. West Indians of African descent may have increased susceptibility to infection with both HTLV-I and HTLV-III.
Management of maternal phenylketonuria.
Authors: L J Arthur, H Gray
Journal: BMJ (1979)

28 % oxygen, her PaO2 was 20-22 kPa and PaCO2 4-5 kPa.Prior to her return to the ward she was started on aminophylline suppositories 360 mg twice daily, prednisolone 20 mg twice daily, salbutamol, and becotide inhalers.Three days later she had three grand mal seizures within one hour, commencing on the right side of her body.Intravenous diazepam (10 mg) given after the first seizure did not prevent the two further attacks.Treatment with aminophylline suppositories was stopped and no further fits occurred.An electro- encephalogram on the following day was normal.In children, convulsions have followed the rectal administration of aminophylline,l but this effect has rarely been described in adults.Absorption from suppositories is unpre- dictable.2In adults convulsions have occurred following intravenous administration.:The patient described above was given 720 mg/day =0-8 mg aminophylline/kg/h for three days.It has been recommended that adults with severe asthma should be given no more than 1 g/day of aminophylline intravenously,4 or no more than 0-9 mg/kg/h.5This case illustrates the danger of aminophylline suppositories and prolonged treatment at high doses.We suggest that this drug should be prescribed by weight at specified intervals rather than in terms of the number of tablets or suppositories, particularly in small adults.
RANDOMISED PLACEBO-CONTROLLED TRIAL COMPARING OXPRENOLOL WITH DISOPYRAMIDE PHOSPHATE IN IMMEDIATE TREATMENT OF SUSPECTED MYOCARDIAL INFARCTION
Authors: R.G. Wilcox, J.R. Hampton, J.M. Rowley, J.R.A. Mitchell, J.M. Roland, D.C. Banks
Journal: The Lancet (1980)
Experience with Ultrasound Miniprobes in the Staging of Colorectal Cancer
Authors: B. Krakamp, M. Parusel, M. Weber, C. Brincker
Journal: Endoscopy (2004)

In the July 2002 edition of Endoscopy, Tseng et al. [1] reported on their experience using an Olympus balloon-sheathed miniprobe for endosonographic examination during diagnostic colonoscopy for colon cancer. There was 85 % agreement between the miniprobe findings and the intraoperatively identified tumor spread. Lymph nodes were identified correctly, with sensitivity and specificity rates of 74 % and 71 %, respectively - a rate that is higher than that achieved with radiographic methods. In contrast to conventional endosonography, the miniprobe was generally found to be particularly suited to investigating proximal and stenotic segments of the colon, particularly in T1 and T2 tumors. The specificity and sensitivity rates were highest in the rectum, for anatomical reasons.
Body Image Disorders
Authors: Philip Snaith
Journal: Psychotherapy and Psychosomatics (1992)

The concepts of disorders of body image are reviewed from three aspects: sociocultural, neurological and psychiatric disorders. Particular attention is paid to the construct of body dysmorphic disorder as defined in the DSMIII-R and the separation of this from somatic delusional disorder. The recognition of associated psychopathology will frequently lead to successful treatment before too much time is spent on fruitless attempts at treatment of the presenting complaint.
Beriberi in Bethnal Green.
Authors: A K Clarke
Journal: BMJ (1971)

responses, some of which might promote either heamorrhage or its deleterious effects.Clearly, these data should be studied before a new therapeutic regimen is tested in man.Recent work suggests that after haemorrhage Nature herself cannot constrict the intestinal bed by sympathetic means and has resorted to the use of vasopressin. 1 12 I am, etc.,
Research methods and reporting
Authors: T. Groves
Journal: BMJ (2008)

A new section of the BMJ about how to do and write up research

Nearly 15 years ago Doug Altman, the BMJ ’s senior statistical adviser and professor of medical statistics, asked in this journal, “What should we think about researchers who use the wrong techniques (either wilfully or in ignorance), use the right techniques wrongly, misinterpret their results, report their results selectively, cite the literature selectively, and draw unjustified conclusions? We should be appalled. Yet numerous studies of the medical literature, in both general and specialist journals, have shown that all of the above phenomena are common.”1

Things may have improved somewhat since then, but we still have much to do. Like most other medical journal editors, we at the BMJ continue to be dismayed by submissions that describe poorly conducted studies and by reports of apparently adequate studies that are so incomplete and confusingly written that they are impossible to appraise. Many of these unsatisfactory articles come from well resourced countries, …
PREVALENCE, PREDICTORS AND EFFECTS OF NESIRITIDE ON CHANGES IN RENAL FUNCTION DURING HOSPITALIZATION FOR ACUTE DECOMPENSATED HEART FAILURE: RESULTS FROM ASCEND-HF
Authors: V M van Deursen, Adrian Hernandez, Amanda Stebbins, Victor Hasselblad, Justin Ezekowitz, Robert Califf, Stephen Gottlieb, Christopher O'Connor, Randall Starling, Wilson Tang, John McMurray, Kenneth Dickstein
Journal: Journal of the American College of Cardiology (2013)
Lack of benefit from cytokine mobilized stem cell therapy for acute myocardial infarction in nonhuman primates
Authors: Andrew E. Arai, Farooq Sheikh, Kwabena O. Agyeman, Robert Hoyt, bandana Sachdev, Xu-Xi Yu, Hong San, Mark Metzger, Cynthia Dunbar, Donald Orlic
Journal: Journal of the American College of Cardiology (2003)
In Vivo Gene Transfer into Adult Stem Cells in Unconditioned Mice by in Situ Delivery of a Lentiviral Vector
Authors: D. Nicole Worsham, Todd Schuesler, Christof von Kalle, Dao Pan
Journal: Molecular Therapy (2006)

The potential of in vivo lentivirus-mediated bone marrow stem cell gene transfer by bone cavity injection, which could take full advantage of any source of stem cells present there, has not been previously explored. Such an approach may avoid several difficulties encountered by ex vivo hematopoietic stem cell (HSC) gene transfer. We sought to determine if efficient gene transfer could be achieved in HSC and mesenchymal stem/progenitor cells (MSC) by intrafemoral injection of a lentivirus vector in mice. Four months after injection, up to 12% GFP-expressing cells were observed in myeloid and lymphoid subpopulations. Significant transduction efficiencies were seen in Lin(-)c-kit(+)Sca1(+) HSC/progenitors and CFU with multilineage potential, which were also confirmed by duplex PCR analysis of progenitor-derived colonies. Four months after secondary BMT, we observed 8.1 to 15% vector(+) CFU in all recipients. Integration analysis by LAM-PCR demonstrated that multiple transduced clones contributed to hematopoiesis in these animals. We also showed that GFP-expressing MSC retained multilineage differentiation potential, with 2.9 to 8.8% GFP-containing CFU-fibroblasts detected in both injected and BMT recipients. Our data provide evidence that adult stem cells in bone marrow can be efficiently transduced "in situ" by in vivo vector administration without preconditioning. This approach could lead to a novel application for treatment of human diseases.
Sustained Zero‐Order Release of Intact Ultra‐Stable Drug‐Loaded Liposomes from an Implantable Nanochannel Delivery System
Authors: Christian Celia, Silvia Ferrati, Shyam Bansal, Anne L. van de Ven, Barbara Ruozi, Erika Zabre, Sharath Hosali, Donatella Paolino, Maria Grazia Sarpietro, Daniel Fine, Massimo Fresta, Mauro Ferrari, Alessandro Grattoni
Journal: Advanced Healthcare Materials (2013)

Metronomic chemotherapy supports the idea that long-term, sustained, constant administration of chemotherapeutics, currently not achievable, could be effective against numerous cancers. Particularly appealing are liposomal formulations, used to solubilize hydrophobic therapeutics and minimize side effects, while extending drug circulation time and enabling passive targeting. As liposome alone cannot survive in circulation beyond 48 h, sustaining their constant plasma level for many days is a challenge. To address this, we develop, as a proof of concept, an implantable nanochannel delivery system and ultra-stable PEGylated lapatinib-loaded liposomes, and we demonstrate the release of intact vesicles for over 18 d. Further, we investigate intravasation kinetics of subcutaneously delivered liposomes and verify their biological activity post nanochannel release on BT474 breast cancer cells. The key innovation of this work is the combination of two nanotechnologies to exploit the synergistic effect of liposomes, demonstrated as passive-targeting vectors and nanofluidics to maintain therapeutic constant plasma levels. In principle, this approach could maximize efficacy of metronomic treatments.
RELATIONSHIP OF CORONARY VASOMOTOR FUNCTION TO MEAN RADIATION DOSE TO THE HEART IN CANCER SURVIVORS
Authors: John D. Groarke, Anju Nohria, Javid Moslehi, Jon Hainer, Viviany Taqueti, Joseph Killoran, Courtney Foster, Mariya Gaber, Ron Blankstein, Sharmila Dorbala, Harvey Mamon, Marcelo Di Carli
Journal: Journal of the American College of Cardiology (2014)
Diagnosis of multinodular goiter by endoscopic ultrasound-guided fine-needle aspiration
Authors: S. Varadarajulu, D. Jhala, C. Canon
Journal: Endoscopy (2006)

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been used to diagnose a variety of mediastinal masses, including lymphoma, neurogenic tumors, sarcoidosis, and malignant metastasis [1]. We report here a patient with a large superior mediastinal mass that was diagnosed as multinodular goiter by means of EUS-FNA.
Effect of the addition of a “help” question to two screening questions on specificity for diagnosis of depression in general practice: diagnostic validity study
Authors: B Arroll, F Goodyear Smith, N Kerse, T Fishman, J Gunn
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To determine the validity of two written screening questions for depression with the addition of a question inquiring if help is needed. <b>Design</b>Cross sectional validation study. <b>Setting</b> 19 general practitioners in six clinics in New Zealand. <b>Participants</b> 1025 consecutive patients receiving no psychotropic drugs. <b>Main outcome measures</b> Sensitivity, specificity, and likelihood ratios of the two screening questions, the help question, combinations of the screening and help questions, and diagnosis by general practitioners. <b>Results</b> The help question alone had a sensitivity of 75% (95% confidence interval 60% to 85%) and a specificity of 94% (93% to 96%). The positive likelihood ratio for the help question was 13.0 (9.5 to 17.8) and the negative likelihood ratio was 0.27 (0.17 to 0.44). The likelihood ratio for patients wanting help today was 17.5 (11.8 to 31.9). The general practitioner diagnosis had a sensitivity of 79% (65% to 88%) and a specificity of 94% (92% to 95%). <b>Conclusion</b> Adding a question inquiring if help is needed to the two screening questions for depression improves the specificity of a general practitioner diagnosis of depression.
Prescribed exercise in people with fibromyalgia: parallel group randomised controlled trial
Authors: Selwyn C M Richards, David L Scott
Journal: BMJ (2002)

Objectives: To evaluate cardiovascular fitness exercise in people with fibromyalgia Design: Randomised controlled trial Setting: Hospital rheumatology outpatients. Group based classes took place at a "healthy living centre." Participants: 132 patients with fibromyalgia. Interventions: Prescribed graded aerobic exercise (active treatment) and relaxation and flexibility (control treatment). Main outcome measures: Participants' self assessment of improvement, tender point count, impact of condition measured by fibromyalgia impact questionnaire, and short form McGill pain questionnaire. Results: Compared with relaxation exercise led to significantly more participants rating themselves as much or very much better at three months: 24/69 (35%) v 12/67 (18%), P=0.03. Benefits were maintained or improved at one year follow up when fewer participants in the exercise group fulfilled the criteria for fibromyalgia (31/69 v 44/67, P=0.01). Peoplein the exercise group also had greater reductions in tender point counts (4.2 v 2.0, P=0.02) and in scores on the fibromyalgia impact questionnaire (4.0 v 0.6, P=0.07). Conclusions: Prescribed graded aerobic exercise is a simple, cheap, effective, and potentially widely available treatment for fibromyalgia.
UK heart surgeons are among the best in the world
Authors: Zosia Kmietowicz
Journal: BMJ (2004)

The most thorough investigation ever into individual surgeons' performance at the operating table has found that the United Kingdom's cardiac surgeons are among the best in the world, with more adults surviving surgery despite patients being sicker and older than elsewhere.

All 222 cardiac surgeons who operate on adults in the United Kingdom met safety limits laid down by the Society of Cardiothoracic Surgeons, with none working at a mortality higher than 6% for coronary bypass surgery and many with much lower rates.



Of almost 25 000 bypass operations done in the United Kingdom each year, the average mortality for 2003 was 1.8%, …
A question of balance: ups and downs of mucosal inflammation.
Authors: M F Kagnoff
Journal: Journal of Clinical Investigation (1994)

Cytokines such as IL-I, TNFa, GM-CSF, and members of the chemokine a and 3 family (e.g., IL-8, MCP-l), have marked proinflammatory effects.These proinflammatory effects can be countered, in part, by other cytokines that have potent anti- inflammatory activities (e.g., TGF-P3I, or by the binding of proinflammatory cytokines to soluble cytokine receptors in the extracellular milieu.In the case of IL-i, an additional novel mechanism can downregulate its proinflammatory activity. Thi involves the production and secretion of a naturally occurring protein, termed IL-i receptor antagonist (IL-lra).IL-Ira is structurally related to IL-1 and binds to type I IL-1 receptors.Since IL-lra has no intrinsic signaling activity through the IL- 1 receptor, it, in effect, blocks this receptor.Administration of sufficient quantities of IL-ira can decrease the inflammatory response in a number of model systems in which an important proinflammatory role of IL-1 has been documented (1).How- ever, less is known regarding the importance of endogenously produced IL-Ira in downregulating the inflammatory response in vivo in acute inflammatory reactions in which IL-1 has a documented role.In this issue of the JCI, Ferretti et al.(2) add to our knowl- edge in this area through studies using a model of acute colitis.This model involves the induction of an acute colitis in rabbits
Ultrasound and Diagnosis of Hydrops of the Gallbladder
Authors: Michael Flynn
Journal: JAMA (1977)

<h3>To the Editor.—</h3> While we agree that ultrasound is a useful emergency procedure in the diagnosis of acute gallbladder disease, we have to take exception to several features in the article by Chandnani et al. First, although the images submitted do show cholelithiasis, measurement of the gallbladder using the centimeter markers included on the scans show the gallbladder to measure approximately 7×3.5 cm. This belies the 7 × 7.5-cm measurement mentioned in the paper and is within the range of normal provided in the references by the authors. To justify the diagnosis of hydrops, stones must be seen in the region of the gallbladder neck or cystic ducts. The stones shown by the authors lie free in the gallbladder lumen. Additionally, we agree with Leopold et al<sup>1</sup>and Lawson<sup>2</sup>that there is a wide range of normal gallbladder diameters, and use of these measurements to diagnose cystic duct
Nitinol radius stent induces less platelet aggregation than stainless steel Palmaz-Schatz/Glanturco-Rubin II stents
Authors: T. Isshiki, K. Eto, M. Ochini, H. Milani, K. Kondo, S. Takoshita, T. Sato
Journal: Journal of the American College of Cardiology (1998)
Part of a Clinical Lecture on Corymbiform Arrangement of Eruptions as Indicative of Nerve-Causation
Authors: J. Hutchinson
Journal: BMJ (1876)

I shall now endeavour to sum up for you the conclusions which I draw from a revicev of the history of electrolysis in aneurism, and my own experience of its working.I beg you to understand that I speak tentatively only ; that I am not inclined to dogmatise.I.In aortic aneurisni, electrolysis is available to prevent external lhzrmorrhage ; and in such cases the operation should be prolonged, that it may occupy, so far as is possible, the external sac -ith the electrolytic products.2. Even w%vhen the aneurism has not penetrated the wall of the thorax or abldomen, electrolysis may be hopefully used after a trial of other remedies, but should not be pushed to the same extenit.3. In external aneurisms, electrolysis should be tried, if compression l)e not available, or have failed; and is to be preferred to ligature-at least of the ininomiiniate and iliac arteries.4. Both poles ought to be inserted, unless the ancurism be fusiform, or too small to admit them.5. If only one pole be used, the positive should be inserted, because its clot is firmer and more adherent, thouah smaller.6.The needles oulght to be insulated, by means of vulcanite.7. The battery shlould have large electromotor force.If both poles be inserted, from four to six cells of medium size slhould be used ; if one oiily, a large iutimber of cells of smaller size are required.
Hard decisions will have to be made: view from intensive care
Authors: Richard Marsh
Journal: BMJ (2006)

Human mortality from the H5N1 strain of influenza has been high even when antiviral drugs have been used. In most cases death has been due to respiratory failure leading to multisystem failure.1 These conditions can be managed by mechanical ventilation and organ system support in intensive care units. Such treatments were not generally available during the previous influenza pandemics in 1918, 1957 and 1968, and they will hopefully reduce the excess mortality if the H5N1 strain produces a pandemic. This will be possible only if the limited critical care resources in the UK are used effectively.

Disappointingly, the Health Protection Agency's pandemic plan for influenza does not mention intensive care,2 although the Department of Health has established a critical care contingency planning group. Critical care networks have also been asked to assess the scope for increasing critical care capacity in an emergency.

We can estimate the extra demand for intensive care from predictions of the likely extent of the epidemic. The Health Protection Agency …