tbuckley/cabot-search huggingface dataset:
A 5-year follow-up study of Alfredson's heel-drop exercise programme in chronic midportion Achilles tendinopathy
Authors: A van der Plas, S de Jonge, R J de Vos, H J L van der Heide, J A N Verhaar, A Weir, J L Tol
Journal: British Journal of Sports Medicine (2011)

Background Eccentric exercises have the most evidence in conservative treatment of midportion Achilles tendinopathy. Although short-term studies show significant improvement, little is known of the long-term (&gt;3 years) results. Aim To evaluate the 5-year outcome of patients with chronic midportion Achilles tendinopathy treated with the classical Alfredson's heel-drop exercise programme. Study design Part of a 5-year follow-up of a previously conducted randomised controlled trial. Methods 58 patients (70 tendons) were approached 5 years after the start of the heel-drop exercise programme according to Alfredson. At baseline and at 5-year follow-up, the validated Victorian Institute of Sports Assessment–Achilles (VISA-A) questionnaire score, pain status, alternative treatments received and ultrasonographic neovascularisation score were recorded. Results In 46 patients (58 tendons), the VISA-A score significantly increased from 49.2 at baseline to 83.6 after 5 years (p&lt;0.001) and from the 1-year to 5-year follow-up from 75.0 to 83.4 (p&lt;0.01). 39.7% of the patients were completely pain-free at follow-up and 48.3% had received one or more alternative treatments. The sagittal tendon thickness decreased from 8.05 mm (SD 2.1) at baseline to 7.50 mm (SD 1.6) at the 5-year follow-up (p=0.051). Conclusion At 5-year follow-up, a significant increase of VISA-A score can be expected. After the 3-month Alfredson's heel-drop exercise programme, almost half of the patients had received other therapies. Although improvement of symptoms can be expected at long term, mild pain may remain.
IMMUNOREACTIONS INVOLVING PLATELETS
Authors: N. Raphael Shulman
Journal: The Journal of Experimental Medicine (1958)

Quantitative aspects of platelet agglutination and inhibition of clot retraction by the antibody of quinidine purpura were described. The reactions appeared to depend on formation of types of antibody-quinidine-platelet complexes which could fix complement but complement was not necessary for these reactions. Complement fixation was at least 10 times more sensitive than platelet agglutination or inhibition of clot retraction for measurement and detection of antibody activity. Although it has been considered that antibodies of drug purpura act as platelet lysins in the presence of complement and that direct lysis of platelets accounts for development of thrombocytopenia in drug purpura, the present study suggests that attachment of antibody produces a change in platelets which is manifested in vitro only by increased susceptibility to non-specific factors which can alter the stability of platelets in the absence of antibody. The attachment of antibody to platelets in vivo may only indirectly affect platelet survival. In contrast to human platelets, dog, rabbit, and guinea pig platelets, and normal or trypsin-treated human red cells did not agglutinate, fix complement, or adsorb antibody; and intact human endothelial cells did not fix complement or adsorb antibody. Rhesus monkey platelets were not agglutinated by the antibody but did adsorb antibody and fix complement although their activity in these reactions differed quantitatively from that of human platelets. Cinchonine could be substituted for quinidine in agglutination and inhibition of clot retraction reactions but quinine and cinchonidine could not. Attempts to cause passive anaphylaxis in guinea pigs with the antibody of quinidine purpura were not successful.
Anticipation requires adaptation
Authors: Christian Balkenius, Peter Gärdenfors
Journal: Behavioral and Brain Sciences (2008)

Abstract To successfully interact with a dynamic world, our actions must be guided by a continuously changing anticipated future. Such anticipations must be tuned to the processing delays in the nervous system as well as to the slowness of the body, something that requires constant adaptation of the predictive mechanisms, which in turn require that sensory information be processed at different time-scales.
Intensity-Modulated Radiation Therapy Dose Prescription, Recording, and Delivery: Patterns of Variability Among Institutions and Treatment Planning Systems
Authors: Indra J. Das, Chee-Wai Cheng, Kashmiri L. Chopra, Raj K. Mitra, Shiv P. Srivastava, Eli Glatstein
Journal: JNCI Journal of the National Cancer Institute (2008)

Intensity-modulated radiation therapy (IMRT) is a widely accepted method for radiation treatment to provide a prescribed and uniform dose to the target volume and a minimum dose to normal tissues that is dependent on the IMRT software and the treatment machine. We examined the variation in IMRT dose prescription, treatment planning, dose recording, and dose delivery among cancer patients who were treated with different treatment planning systems at different medical institutions to assess variability in patient care.We conducted a retrospective analysis of 803 patients who were treated with IMRT between October 2004 and July 2006 for brain, head and neck, or prostate cancer at five medical institutions that used different treatment planning systems. The prescribed dose to the target volume, as recorded in the chart or as noted in the electronic data management system, was extracted for each patient. The planned dose that was delivered to the patient, as represented in the dose-volume histogram, was acquired from each treatment planning system. The actual minimum, maximum, median, and isocenter doses to the target volume were normalized to the prescribed dose and analyzed for each disease site and institution.Of the 803 patients, 12% were treated for brain cancer, 26% for head and neck cancer, and 62% for prostate cancer. The recorded dose variability from prescription was widespread for the minimum, maximum, and isocenter doses. A total of 46% of the patients received a maximum dose that was more than 10% higher than the prescribed dose, and 63% of the patients received a dose that was more than 10% lower than the prescribed dose. At all five institutions, the prostate cancer cases had the smallest dosimetric variation and the head and neck cancer cases had the largest variation. The median dose to the target varied from the prescribed dose by +/-2% in 68% of the patients, by +/-5% in 88% of the patients, and by +/-10% in 96% of the patients. The recorded isocenter dose varied from prescription for all disease sites and treatment planning systems.Substantial variation in the prescribed and delivered doses exists among medical institutions, raising concerns about the validity of comparing clinical outcomes for IMRT. The isocenter dose in IMRT is simply a point dose and often does not reflect the prescription dose that is specified by a selected isodose line encompassing the target volume. This study suggests the need for national and/or international guidelines for dose prescription, planning, and reporting for a meaningful clinical trial in IMRT.
Ovarian Cancer Cell Detachment and Multicellular Aggregate Formation Are Regulated by Membrane Type 1 Matrix Metalloproteinase: A Potential Role in I.p. Metastatic Dissemination
Authors: Natalie M. Moss, Maria V. Barbolina, Yueying Liu, Limin Sun, Hidayatullah G. Munshi, M. Sharon Stack
Journal: Cancer Research (2009)

Abstract An early event in the metastasis of epithelial ovarian carcinoma is shedding of cells from the primary tumor into the peritoneal cavity followed by diffuse i.p. seeding of secondary lesions. Anchorage-independent metastatic cells are present as both single cells and multicellular aggregates (MCA), the latter of which adhere to and disaggregate on human mesothelial cell monolayers, subsequently forming invasive foci. Although this unique metastatic mechanism presents a distinct set of therapeutic challenges, factors that regulate MCA formation and dissemination have not been extensively evaluated. Proteolytic activity is important at multiple stages in i.p. metastasis, catalyzing migration through the mesothelial monolayer and invasion of the collagen-rich submesothelial matrix to anchor secondary lesions, and acquisition of membrane type 1 matrix metalloproteinase (MT1-MMP; MMP-14) expression promotes a collagen-invasive phenotype in ovarian carcinoma. MT1-MMP is regulated posttranslationally through multiple mechanisms including phosphorylation of its cytoplasmic tail, and the current data using ovarian cancer cells expressing wild-type, phosphomimetic (T567E-MT1-MMP), and phosphodefective (T567A-MT1-MMP) MT1-MMP show that MT1-MMP promotes MCA formation. Confluent T567E-MT1-MMP–expressing cells exhibit rapid detachment kinetics, spontaneous release as cell-cell adherent sheets concomitant with MT1-MMP–catalyzed α3 integrin ectodomain shedding, and robust MCA formation. Expansive growth within three-dimensional collagen gels is also MT1-MMP dependent, with T567E-MT1-MMP–expressing cells exhibiting multiple collagen invasive foci. Analysis of human ovarian tumors shows elevated MT1-MMP in metastases relative to paired primary tumors. These data suggest that MT1-MMP activity may be key to ovarian carcinoma metastatic success by promoting both formation and dissemination of MCAs. [Cancer Res 2009;69(17):7121–9]
Dog mastocytoma cells produce transforming growth factor beta 1.
Authors: D W Pennington, A R Lopez, P S Thomas, C Peck, W M Gold
Journal: Journal of Clinical Investigation (1992)

Transforming growth factor-beta (TGF beta) promotes deposition of extracellular matrix and is associated with fibrotic conditions both in experimental animals and in humans. Although a role for mast cells has been suspected in the pathogenesis of fibrosis, no potent mediator capable of stimulating fibroblast growth or extracellular matrix deposition has been identified in mast cell supernatants. We report here the constitutive production of TGF beta 1 by four dog mastocytoma cell lines. TGF beta 1 was identified by characteristic biologic activity, blockade of biologic effect by specific neutralizing antibody, and by recognition of a band with the appropriate migration by western blot. TGF beta 1 mRNA, but not TGF beta 2 or TGF beta 3 mRNA, was also produced constitutively by all four cell lines. Quantitation by bioassay revealed baseline TGF beta secretion of approximately 1 ng/10(6) cells over 48 h. Stimulation of mastocytoma cells with phorbol ester increased the rate of release of TGF beta 1, most markedly in the first 30 min after stimulation, without increasing TGF beta 1 mRNA. Dog mastocytoma cells produced TGF beta 1 primarily in a latent form, inactive until treated with acid. Both pure TGF beta 1 and TGF beta-containing mastocytoma cell-conditioned media inhibited mitogenesis and proliferation in dog mastocytoma cell lines, suggesting that mast cell tumor lines would not grow preferentially based on their ability to produce TGF beta. These studies may make possible further investigation of the mechanism by which mast cells contribute to the induction of fibrosis.
The Impact of ADHD and Autism Spectrum Disorders on Temperament, Character, and Personality Development
Authors: Henrik Anckarsäter, Ola Stahlberg, M. Tomas Larson, Catrin Hakansson, Sig-Britt Jutblad, Lena Niklasson, Agneta Nyden, Elisabet Wentz, Stefan Westergren, C. Robert Cloninger, Christopher Gillberg, Maria Rastam
Journal: American Journal of Psychiatry (2006)

Objective: The authors describe personality development and disorders in relation to symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders. Method: Consecutive adults referred for neuropsychiatric investigation (N=240) were assessed for current and lifetime ADHD and autism spectrum disorders and completed the Temperament and Character Inventory. In a subgroup of subjects (N=174), presence of axis II personality disorders was also assessed with the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). Results: Patients with ADHD reported high novelty seeking and high harm avoidance. Patients with autism spectrum disorders reported low novelty seeking, low reward dependence, and high harm avoidance. Character scores (self-directedness and cooperativeness) were extremely low among subjects with neuropsychiatric disorders, indicating a high overall prevalence of personality disorders, which was confirmed with the SCID-II. Cluster B personality disorders were more common in subjects with ADHD, while cluster A and C disorders were more common in those with autism spectrum disorders. The overlap between DSM-IV personality disorder categories was high, and they seem less clinically useful in this context. Conclusions: ADHD and autism spectrum disorders are associated with specific temperament configurations and an increased risk of personality disorders and deficits in character maturation.
Alterations of L-Type Calcium Current and Cardiac Function in CaMKIIδ Knockout Mice
Authors: Lin Xu, Dongwu Lai, Jun Cheng, Hyun Joung Lim, Thitima Keskanokwong, Johannes Backs, Eric N. Olson, Yanggan Wang
Journal: Circulation Research (2010)

Rationale : Recent studies have highlighted important roles of CaMKII in regulating Ca 2+ handling and excitation-contraction coupling. However, the cardiac effect of chronic CaMKII inhibition has not been well understood. Objective : We have tested the alterations of L-type calcium current (I Ca ) and cardiac function in CaMKIIδ knockout (KO) mouse left ventricle (LV). Methods and Results : We used the patch-clamp method to record I Ca in ventricular myocytes and found that in KO LV, basal I Ca was significantly increased without changing the transmural gradient of I Ca distribution. Substitution of Ba 2+ for Ca 2+ showed similar increase in I Ba . There was no change in the voltage dependence of I Ca activation and inactivation. I Ca recovery from inactivation, however, was significantly slowed. In KO LV, the Ca 2+ -dependent I Ca facilitation (CDF) and I Ca response to isoproterenol (ISO) were significantly reduced. However, ISO response was reversed by β2-adrenergic receptor (AR) inhibition. Western blots showed a decrease in β1-AR and an increase in Ca v 1.2, β2-AR, and Gαi3 protein levels. Ca 2+ transient and sarcomere shortening in KO myocytes were unchanged at 1-Hz but reduced at 3-Hz stimulation. Echocardiography in conscious mice revealed an increased basal contractility in KO mice. However, cardiac reserve to work load and β-adrenergic stimulation was reduced. Surprisingly, KO mice showed a reduced heart rate in response to work load or β-adrenergic stimulation. Conclusions : Our results implicate physiological CaMKII activity in maintaining normal I Ca , Ca 2+ handling, excitation-contraction coupling, and the in vivo heart function in response to cardiac stress.
Screening and brief intervention for excessive alcohol use: qualitative interview study of the experiences of general practitioners
Authors: A. Beich
Journal: BMJ (2002)

To explore the suitability of a screening based intervention for excessive alcohol use by describing the experiences of general practitioners who tried such an intervention in their everyday practice.Qualitative interviews with general practitioners who had participated in a pragmatic study of a combined programme of screening and a brief intervention for excessive alcohol use. Doctors were interviewed either individually or in focus groups. A computer based, descriptive, phenomenological method was used to directly analyse the digitally recorded interviews.24 of 39 general practitioners in four Danish counties who volunteered to take part in the pragmatic study were interviewed.The doctors were surprised at how difficult it was to establish rapport with the patients who had a positive result on the screening and to ensure compliance with the intervention. Although the doctors considered the doctor-patient relationship robust enough to sustain targeting of alcohol use, they often failed to follow up on initial interventions, and some expressed a lack of confidence in their ability to counsel patients effectively on lifestyle issues. The doctors questioned the rationale of screening in young drinkers who may grow out of excessive drinking behaviour. The programme needed considerable resources, and it interrupted the natural course of consultations and was inflexible. The doctors could not recommend the screening and brief intervention programme, although they thought it important to counsel their patients on drinking.Screening for excessive alcohol use created more problems than it solved for the participating doctors. The results underline the value of carrying out pragmatic studies on the suitability of seemingly efficacious healthcare programmes.
Is the general population well informed about tuberculosis
Authors: Mirjana Trajcevska, Aleksandar Sandevski, Ljiljana Simonovska
Journal: European Respiratory Journal (2014)

People nowadays are mostly occupied with their existential problems so they don9t pay much attention on their helath condition and helath education.  The aim of this survey was to discover whether citizens have a proper health education about TB.  Patients and metods: we tested 387 persons (203 males and 184 females) asking them a battery of 32 questions: Do they know that TB is an infectious disease? Is this disease a shameful one? Is there any protection against TB? Is TB a curable disease? etc.  Results: these questionnaires showed differences in basic knowledge for TB according to their age, gender, level of education, place of living and social status. Chi-square test showed statistically significant differences (p  Conclusions:  1.The general conclusion is that the citizens have a low level of health education about TB because of lack of information in school as well as in the mass media.  2. there were differences in basic knowledge according to their: age, level of education, place of living and their socio-economic status.
Recombinant soluble human Fc gamma RII: production, characterization, and inhibition of the Arthus reaction.
Authors: F L Ierino, M S Powell, I F McKenzie, P M Hogarth
Journal: The Journal of Experimental Medicine (1993)

A recombinant soluble form of human Fc gamma RII (rsFc gamma RII) was genetically engineered by the insertion of a termination codon 5' of sequences encoding the transmembrane domain of a human Fc gamma RII cDNA. Chinese hamster ovary cells were transfected with the modified cDNA and the secreted rsFc gamma RII purified from the tissue culture supernatant (to &amp;gt; 95%, assessed by SDS-PAGE) using heat aggregated human immunoglobulin G (IgG) immunoaffinity chromatography. The IgG-purified rsFc gamma RII was relatively homogeneous (approximately 31,000 M(r)) whereas the total unpurified rsFc gamma RII secreted into the tissue culture supernatant was heterogeneous relating to N-linked glycosylation differences. Functional in vitro activity of the rsFc gamma RII was demonstrated by: (a) ability to bind via the Fc portion of human IgG and mouse IgG (IgG2a &amp;gt; IgG1 &amp;gt; &amp;gt; IgG2b); (b) complete inhibition of binding of erythrocytes sensitized with rabbit IgG to membrane-bound Fc gamma RII on K562 cells; and (c) inhibition of the anti-Leu4-induced T cell proliferation assay. Blood clearance and biodistribution studies show the rsFc gamma RII was excreted predominantly through the kidney in a biphasic manner, with an alpha-phase (t1/2 approximately 25 min) and a beta-phase (t1/2 approximately 4.6 h); the kidneys were the only organs noted with tissue-specific accumulation. In vivo, the administration of rsFc gamma RII significantly inhibited the immune complex-mediated inflammatory response induced by the reversed passive Arthus reaction model in rats. There was a specific and dose-dependent relationship between the amount of rsFc gamma RII administered, and the reduction in the size and severity of the macroscopic inflammatory lesion. Histological analysis of the skin showed a diffuse neutrophil infiltrate in both control and rsFc gamma RII-treated rats, however the perivascular infiltrate and the red cell extravasation was less intense in the rsFc gamma RII-treated group. It is likely that complement activation leads to neutrophil chemotaxis, but neutrophil activation via Fc gamma RII, which results in inflammatory mediator release, is inhibited. The data indicate that rsFc gamma RII is a potential therapeutic agent for the treatment of antibody or immune complex-mediated tissue damage.
Easy-to-Use Decision Aids for Improved Cancer Family History Collection and Use Among Oncology Practices
Authors: Aisha S. Sie, Han G. Brunner, Nicoline Hoogerbrugge
Journal: Journal of Clinical Oncology (2014)

the underreporting of family history in patients with breast and colorectal cancer.Lu et al 2 lay out reasons and proposed that time has come to improve family history collection.We fully agree with this statement but believe that more needs to be done.In our opinion the primary barriers to overcome are improving not only the collection but also the interpretation of cancer family history. 3e conclude from a recent randomized controlled trial (Dekker et al, submitted for publication) that education of clinicians does not improve the referral rate for genetic counseling of those at high risk.This led to our development of an easy-to-use digital referral test that guides clinicians and patients through appropriate family history collection and provides an instant conclusion regarding the presence or absence of an increased hereditary cancer risk.We also evaluated this referral test for usability.By using the referral test, nonmedical personnel gave the correct advice in 84% of patient cases, 4 whereas a group of doctors (general practitioners, geneticists, surgeons and gastroenterologists) without use of this referral test gave the correct advice for less than 65% of such patients. 5This referral test is available in multiple languages (English, German, and Dutch) for breast/ovarian cancer, colorectal cancer, and pediatric cancer at www.radboudumc.nl/hereditarycancerand as smartphone apps (as of yet only available in Dutch).At present, this referral test is used in daily practice by general practitioners as well as oncologists.During many weeks after launch, this was the most downloaded medical app.Most patients fill in the test immediately before their consultation with the oncologist, assisted by a secretary or doctor's assistant.Based on this test result, the oncologist then decides whether referral for genetic counseling is needed and wanted.Therefore to improve the quality of family history and referral for genetic counseling among oncology practices, we argue that education will not suffice: we need to augment this by easy-to-use decision aids to simplify the process of family history collection and interpretation.Our recently developed referral test (app) is one such aid.