tbuckley/cabot-search huggingface dataset:
WANDERING SUBCUTANEOUS SWELLINGS ON THE LIMBS.
Authors: F. PARKES WEBER
Journal: British Journal of Dermatology (1939)

Journal Article WANDERING SUBCUTANEOUS SWELLINGS ON THE LIMBS. Get access F. PARKES WEBER, M.D., F.R.C.P. F. PARKES WEBER, M.D., F.R.C.P. Senior Physician to the German Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 51, Issue 3, 1 March 1939, Pages 132–135, https://doi.org/10.1111/j.1365-2133.1939.tb10661.x Published: 01 March 1939
A review of the specificity of exercises designed for conditioning the lumbar extensors
Authors: James Steele, Stewart Bruce-Low, Dave Smith
Journal: British Journal of Sports Medicine (2013)

To review the specificity of exercises designed to condition the lumbar extensor musculature (ie, lumbar erector spinae and multifidus).A review of studies examining effects of exercises designed to condition the lumbar extensors was conducted. Included were studies that examined the acute activation and chronic adaptation of the lumbar extensor musculature in response to benches and roman chair trunk extensions, free weights exercises (ie, deadlifts, squats, good-mornings, etc), floor and stability ball exercise (ie, trunk extensions, bridging, four-point kneeling, etc) and resistance machines (ie, those with and without pelvic restraints).Evidence suggests that the reviewed exercises designed to condition the lumbar extensors all may result in significant activation of this musculature during their performance. However, examination of training studies shows that for benches and roman chair trunk extensions, free weights exercises, floor and stability ball exercise and resistance machines without appropriate pelvic restraints, evidence suggests that they may be less effective for inducing chronic adaptations in the lumbar extensors as a result of their performance. Contrastingly, resistance machines that employ appropriate pelvic restraint to isolate lumbar extension are better evidenced to confer specific adaptations to the lumbar extensors.Numerous exercise approaches have been designed with the intention of conditioning the lumbar extensors. Those examined appear to activate the lumbar extensors; however, the specificity of many of these exercises for producing chronic adaptations may be questionable, potentially due to the compound nature of them allowing involvement of other musculature such as the hip extensors. Many of the reviewed exercises offer potential to condition the lumbar extensors, however, isolation of lumbar extension through appropriate pelvic restraint appears important for optimising specific adaptations in the lumbar extensors.
The McDonald-Kreitman Test and Slightly Deleterious Mutations
Authors: J. Charlesworth, A. Eyre-Walker
Journal: Molecular Biology and Evolution (2008)

It is possible to estimate the proportion of substitutions that are due to adaptive evolution using the numbers of silent and nonsilent polymorphisms and substitutions in a McDonald and Kreitman-type analysis. Unfortunately, this estimate of adaptive evolution is biased downward by the segregation of slightly deleterious mutations. It has been suggested that 1 way to cope with the effects of these slightly deleterious mutations is to remove low-frequency polymorphisms from the analysis. We investigate the performance of this method theoretically. We show that although removing low-frequency polymorphisms does indeed reduce the bias in the estimate of adaptive evolution, the estimate is always downwardly biased, often to the extent that one would not be able to detect adaptive evolution, even if it existed. The method is reasonably satisfactory, only if the rate of adaptive evolution is high and the distribution of fitness effects for slightly deleterious mutations is very leptokurtic. Our analysis suggests that adaptive evolution could be quite prevalent in humans (>8%) and still not be detectable using current methodologies. Our analysis also suggests that the level of adaptive evolution has probably been underestimated, possibly substantially, in both bacteria and Drosophila.
Medical services at the first Winter Youth Olympic Games 2012 in Innsbruck/Austria
Authors: Cornelia Blank, Patrick Schamasch, Lars Engebretsen, Simon Haslinger, Gerhard Ruedl, Christian Fink, Wolfgang Schobersberger
Journal: British Journal of Sports Medicine (2012)

The Youth Olympic Games (YOG) are a new format designed by the International Olympic Committee. So far no reference data are available regarding the organisation or implementation of the medical services that were needed for the Winter Youth Olympic Games that took place for the first time in Innsbruck 9-24 January 2012.(1) To provide insight into what is needed to prepare for such a complex high level sporting event from a medical perspective, (2) to provide data on medical services for future organising committees and (3) to provide information on different National Olympic Committee (NOC) delegation structures and the consequences of registering a National Olympic Committee Team Physician.A medical information system in the form of a patient data-management system was developed with all involved parties to standardise data collection. All medical encounters occurring at any IYOGOC medical service centre (including physiotherapy and psychology facilities) were tracked and collected in daily reports. Data evaluation was prepared based on different interest groups (Athletes, National Olympic Committees, Workforce, International Olympic Committee and Media) and analysed.327 medical encounters (42.8% athletes; out of these, 57.9% were accounted to athletes with own NOC team physician) were seen during the YOG 2012. The total number of hospital transports was 27.3%, of which 8.9% were hospitalised with an average length of 1.9 nights. Physiotherapy usage was low with only 19 medical encounters resulting in a referral to physiotherapy accounting for 67 treatments during the entire YOG. Psychological care service was not used at all. The main reason for illnesses was disorders of the respiratory system (28.8%), injuries mostly affected upper extremities (49.6%) and were mostly diagnosed with lacerations and contusions (26.2%). Injury (70.7%) and illness (29.3%) incidences in athletes were slightly lower than previous studies showed. 40.0% of NOC delegations registered their own team physicians, which led to a significant difference in usage frequency of medical service (-3%, p=0.012).Medical service coverage at the first Winter Youth Olympic Games seemed to be appropriate. No disaster or epidemic disease challenged the medical service plan. Future organising committees could use the provided data as a reference for their planning efforts.
Biologics in inflammatory bowel disease: how much progress have we made?
Authors: W J Sandborn
Journal: Gut (2004)

Biologic therapies include:(1) naturally occurring or modified biologic compounds such as vaccines (live, live attenuated, or killed microorganisms), hormone extracts, and blood products;(2) recombinant proteins or peptides—for example, granulocyte macrophage colony stimulating factor and growth hormone;(3) monoclonal antibodies and fusion proteins; and (4) antisense oligonucleotides to nucleic acids. These biologic therapies, which are targeted towards specific disease mechanisms, have the potential to provide more effective and safe treatments for human diseases. Clinical trials have demonstrated that inhibition of the cytokine tumour necrosis factor α(TNF) and inhibition of the selective adhesion molecules α4 integrin and α4β7 integrin are effective in the treatment of various forms of the inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn’s disease (CD). It is also clear that drug toxicity related to biologic therapy, including hypersensitivity, serum sickness, autoimmunity, infection, and immunogenicity may occur. This article reviews the progress made to date in the treatment of IBD with biologic therapies, concentrating primarily on the TNF inhibitors infliximab, etanercept, adalimumab, CDP870, CDP571, and onercept, and on the selective adhesion molecule inhibitors natalizumab and MLN-02, but also reviewing other potentially promising therapies targeted towards other mechanisms of action (table 1).

View this table:

 Table 1  
 Biotechnology compounds that have been or are being evaluated for the treatment of patients with inflammatory bowel disease



### Comparative mechanisms of action for various anti-TNF agents

TNF is elevated in the mucosa of patients with CD,1 and inhibition of TNF has been an effective treatment strategy.2 Comparison of various anti-TNF agents with respect to biologic construction, ability to bind soluble and membrane bound TNF, ability to fix complement, ability to mediate antibody dependent cytotoxicity, ability to cause T cell apoptosis, and efficacy in unselected patients versus efficacy primarily in patients with elevated concentrations of C reactive protein (CRP) is shown in table 2. The efficacy of the anti-TNF agent infliximab in unselected patients with …
A system to generate simultaneous forced oscillation and continuous positive airway pressure
Authors: R Farre, M Rotger, JM Montserrat, D Navajas
Journal: European Respiratory Journal (1997)

Assessment of airway obstruction in patients with obstructive sleep apnoea (OSA) subjected to continuous positive airway pressure (CPAP) may be carried out using the forced oscillation technique (FOT). To facilitate routine application of forced oscillation (FO) in sleep studies, our aim was to design a system capable of generating CPAP and applying FOT simultaneously. We constructed a prototype CPAP + FO generator by connecting a specially designed electromagnetic valve in parallel with a conventional blower. The capacity of the prototype to generate forced oscillation (5 Hz +/- 1 hPa) was tested by connecting it to a model simulating spontaneous breathing. The response of the prototype for target CPAPs of 5, 10 and 15 hPa and imposed sinusoidal breathing with peak flow up to 0.75 L x s(-1) was excellent when compared with that reported for commercially available CPAP generators. The applicability of the prototype was tested by applying it to assess airway obstruction in four patients with OSA during sleep. We conclude that the generator designed is able to apply continuous positive airway pressure and forced oscillation simultaneously. The system could be useful for automatic and noninvasive assessment of airway obstruction in patients with obstructive sleep apnoea subjected to continuous positive airway pressure. Future development of the generator may be helpful in implementing a set-up for automatic titration of continuous positive airway pressure.
Tactile acuity and lumbopelvic motor control in patients with back pain and healthy controls
Authors: H Luomajoki, G L Moseley
Journal: British Journal of Sports Medicine (2009)

Background Voluntary lumbopelvic control is compromised in patients with back pain. Loss of proprioceptive acuity is one contributor to decreased control. Several reasons for decreased proprioceptive acuity have been proposed, but the integrity of cortical body maps has been overlooked. We investigated whether tactile acuity, a clear clinical signature of primary sensory cortex organisation, relates to lumbopelvic control in people with back pain. Methods Forty-five patients with back pain and 45 age- and sex-matched healthy controls participated in this cross-sectional study. Tactile acuity at the back was assessed using two-point discrimination (TPD) threshold in vertical and horizontal directions. Voluntary motor control was assessed using an established battery of clinical tests. Results Patients performed worse on the voluntary lumbopelvic tasks than healthy controls did (p&lt;0.001). TPD threshold was larger in patients (mean (SD)=61 (13) mm) than in healthy controls (44 (10) mm). Moreover, larger TPD threshold was positively related to worse performance on the voluntary lumbopelvic tasks (Pearson's r=0.49; p&lt;0.001). Discussion Tactile acuity, a clear clinical signature of primary sensory cortex organisation, relates to voluntary lumbopelvic control. This relationship raises the possibility that the former contributes to the latter, in which case training tactile acuity may aid recovery and assist in achieving normal motor performance after back injury.
Risk Factors for Breast Cancer According to Family History of Breast Cancer
Authors: Graham A. Colditz, Bernard A. Rosner, Frank E. Speizer
Journal: JNCI Journal of the National Cancer Institute (1996)

Background:Family history of breast cancer is an established risk factor for this disease and is used to identify women at higher risk, although the impact of risk factors for breast cancer among women with a family history is not well defined.
Cardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy
Authors: Deborah Grady, David Herrington, Vera Bittner, Roger Blumenthal, Michael Davidson, Mark Hlatky, Judith Hsia, Stephen Hulley, Alan Herd, Steven Khan, L. Kristin Newby, David Waters, Eric Vittinghoff, Nanette Wenger, None for the HERS Research Group
Journal: JAMA (2002)

HE HEART AND ESTROGEN/ progestin Replacement Study (HERS) was a randomized, blinded, placebo-controlled trial of the effect of 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate daily on coronary heart disease (CHD) event risk among 2763 postmenopausal women with documented CHD. 1 Overall, during 4.1 years of follow-up, there were no significant differences between the hormone and placebo groups in the primary outcome of CHD events (nonfatal myocardial infarction [MI] plus CHD-related death) or in any secondary cardiovascular outcomes. 2-5However, post-hoc analyses showed a statistically significant time trend, with more CHD events in the hormone group than in the placebo group during the first year of treatment, and fewer in years 3 to 5. 2 HERS investiga-
A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic T lymphocytes in T cells of smoldering myeloma patients
Authors: J Bae, R Prabhala, A Voskertchian, A Brown, C Maguire, P Richardson, G Dranoff, K C Anderson, N C Munshi
Journal: Leukemia (2014)
Raised gamma-glutamyltransferase activity and the need for liver biopsy.
Authors: A Ireland, L Hartley, N Ryley, J O McGee, J M Trowell, R W Chapman
Journal: BMJ (1991)

patients, however, also had more abdominal signs, and analysis after allowance for rebound tenderness showed that rectal tenderness on the right lost its significance.In women of childbearing age, among whom the rate of appendicectomy at which appendicitis is not found is high, the findings on rectal examination did not correlate significantly with the final diagnosis.TABLE V-Relation between right sided rectal tenderness and acute appendicitis by age and sex No (%) of patients with appendicitis if right sided rectal tenderness: Age Odds 95% Confidence (years) Absent Present ratio interval Male patients 0-33(51) 23(64) 1-72 0-69to 4-35 15-80 (61) 38 (58) 0-88 0-46 to 1-69 30-25 (45) 9 (75) 3-72 0-80 to 24-39 u45 25 (31) 2 (40) 1-49 0-12 to 13-83 Female patients 0-20(44) 25(51)
Remodeling of Gap Junctional Coupling in Hypertrophied Right Ventricles of Rats With Monocrotaline-Induced Pulmonary Hypertension
Authors: Mahmud Uzzaman, Haruo Honjo, Yoshiko Takagishi, Luni Emdad, Anthony I. Magee, Nicholas J. Severs, Itsuo Kodama
Journal: Circulation Research (2000)

The present study investigates the remodeling of gap junctional organization in relation to changes in anisotropic conduction properties in hypertrophied right ventricles (RVs) of rats with monocrotaline (MCT)-induced pulmonary hypertension. In contrast to controls that showed immunolocalization of connexin43 (Cx43) labeling largely confined to the intercalated disks, RV myocytes from MCT-treated rats showed dispersion of Cx43 labeling over the entire cell surface. The disorganization of Cx43 labeling became more pronounced with the progression of hypertrophy. Desmoplakin remained localized to the intercalated disks, as in controls. In RV tissues, the proportion of Cx43 label at the intercalated disk progressively decreased. Quantitative analysis of en face views of intercalated disks revealed a significant decrease in the disk gap junctional density in RV tissues of MCT-treated rats (control, 0.18 versus MCT-treated, 0.14 at 2 weeks; control, 0.16 versus MCT-treated, 0.11 at 4 weeks). Conduction velocity in RVs parallel to the fiber orientation was significantly lower (30.2% [n=9]) in MCT-treated rats at 4 weeks than in control rats, whereas there was no significant difference observed in the conduction velocity across the fiber orientation between control and MCT-treated rats. The anisotropic ratio of MCT-treated rats (1.38+/-0.10) was significantly lower than that of control rats (1.98+/-0.12). These results suggest that RV hypertrophy induced by pressure overload is associated with both disorganization of gap junction distribution and alteration of anisotropic conduction properties.
ACC/AHA/Physician Consortium 2008 Clinical Performance Measures for Adults With Nonvalvular Atrial Fibrillation or Atrial Flutter
Authors: N.A. Mark Estes, Jonathan L. Halperin, Hugh Calkins, Michael D. Ezekowitz, Paul Gitman, Alan S. Go, Robert L. McNamara, Joseph V. Messer, James L. Ritchie, Sam J.W. Romeo, Albert L. Waldo, D. George Wyse
Journal: Journal of the American College of Cardiology (2008)
Multi-targeted therapy with a HER-2/neu-specific vaccine and a VEGF-R2 inhibitor enhances anti-tumor immunity
Authors: Elizabeth A. Manning, John G M Ullman, Timothy R. Hansen, Todd D. Armstrong, Elizabeth M. Jaffee, Leisha A. Emens
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Due to the complexity of tumors and their microenvironment, combinatorial strategies may be more successful in treating cancer than single agents. Therefore, we targeted both tumor cells and the associated vasculature. The proto-oncogene HER-2/ neu (neu) is overexpressed in 30% of breast cancers, confers a poor prognosis, and correlates with increased angiogenesis and expression of vascular endothelial growth factor (VEGF). Neu-specific GM-CSF secreting vaccines induce curative immune responses in non-tolerized FVB mice, but are ineffective in tolerized neu transgenic ( neu -N) mice. The monoclonal antibody DC101 inhibits angiogenic signaling via the VEGF-R2 receptor. To study the potential synergy of tumor immunotherapy and anti-angiogenic therapy, we examined DC101 alone, and in sequence with a neu-targeted vaccine, against established neu-expressing tumors. In FVB mice, systemic administration of DC101 significantly inhibited tumor growth and angiogenesis, and induced apoptosis. Notably, serum VEGF levels were increased by 5-fold. Although VEGF has documented immune suppressive activity, no negative effects on immature myeloid cells, dendritic cell phenotype and activity, or vaccine-induced immunity were observed. Instead, over a two-fold expansion of tumor-specific T cells was detected by ELISPOT. After withdrawing DC101, tumors continued to regress and 50% of mice rejected a second challenge. Combining DC101 and neu-specific vaccination improved tumor regression and lytic activity against tumor cells and neu-expressing target cells. DC101 also enhanced the detection of tumor-infiltrating lymphocytes. Collectively, these results show that DC101 can be effectively combined with active immunotherapy to improve anti-tumor immune responses in a non-tolerant host. In the more clinically relevant neu-N mice, DC101 alone slowed tumor growth, but did not induce regression or T cell activation. Preliminary results show that DC101 with vaccine does not augment the anti-tumor response. Therefore, experiments incorporating immune modulation to mitigate tolerance are ongoing in neu-N mice. In summary, we hypothesize that reducing tumor-associated angiogenesis causes apoptotic tumor cells to shed antigen, thereby enhancing anti-tumor immunity by cross-presentation in the absence of tolerance. Also, normalized vasculature may improve T cell infiltration into tumors. This work supports studies combining tumor immunotherapy and anti-angiogenic therapy, and is the first to examine DC101-induced anti-tumor immune responses. These data support the development of multi-targeted treatments combining active vaccination and anti-angiogenic therapy for clinical translation.
Commercial plasma alpha1-antitrypsin (Prolastin) contains a conformationally inactive, latent component
Authors: DA Lomas, PR Elliott, RW Carrell
Journal: European Respiratory Journal (1997)

Fractionated plasma alpha1-antitrypsin is widely-used as replacement therapy in patients with Z alpha1-antitrypsin deficiency-related emphysema. We have recently shown that purified antitrypsin may be induced to adopt an inactive latent conformation by heating at high temperatures in stabilizing concentrations of sodium citrate. Such a conformation was predicted to be present in commercial preparations of antitrypsin, as these require heating under similar conditions for viral inactivation. Native antitrypsin was purified from plasma, and commercial antitrypsin (Prolastin) was obtained from Bayer Corporation. Western blot analysis of transverse urea gradient (TUG) gels showed that commercial antitrypsin migrated as two bands: one with an unfolding profile of native antitrypsin and the second with a profile of latent antitrypsin. A latent fraction, comprising approximately 8% of the total antitrypsin, was separated from the native antitrypsin in Prolastin by anion exchange chromatography. The specific activity of this latent form against bovine alpha-chymotrypsin increased from 1 to 2% to 50% over 3 h after refolding from 6 M guanidine hydrochloride. These data show that commercial antitrypsin contains a latent component. The significance of this conformation in vivo is unknown, although Prolastin has shown few adverse side-effects in prolonged clinical usage.
If I Could Just Stop Loving You: Anti-Love Biotechnology and the Ethics of a Chemical Breakup
Authors: Brian D. Earp, Olga A. Wudarczyk, Anders Sandberg, Julian Savulescu
Journal: The American Journal of Bioethics (2013)

"Love hurts"—as the saying goes—and a certain amount of pain and difficulty in intimate relationships is unavoidable. Sometimes it may even be beneficial, since adversity can lead to personal growth, self-discovery, and a range of other components of a life well-lived. But other times, love can be downright dangerous. It may bind a spouse to her domestic abuser, draw an unscrupulous adult toward sexual involvement with a child, put someone under the insidious spell of a cult leader, and even inspire jealousy-fueled homicide. How might these perilous devotions be diminished? The ancients thought that treatments such as phlebotomy, exercise, or bloodletting could "cure" an individual of love. But modern neuroscience and emerging developments in psychopharmacology open up a range of possible interventions that might actually work. These developments raise profound moral questions about the potential uses—and misuses—of such anti-love biotechnology. In this article, we describe a number of prospective love-diminishing interventions, and offer a preliminary ethical framework for dealing with them responsibly should they arise.