tbuckley/cabot-search huggingface dataset:
Effects of cycle strategy and fibre composition on muscle glycogen depletion pattern and subsequent running economy
Authors: R Suriano, J Edge, D Bishop
Journal: British Journal of Sports Medicine (2008)

Purpose In this study, the effects of variable and constant-intensity cycling on muscle glycogen depletion patterns and subsequent running economy was examined. 60 minutes of cycling at a constant power (CON) or variable intensity (VAR) followed by a treadmill run to determine running economy was completed by nine male triathletes (Vo 2 max = 67.7 (4.9 ml) kg − min −1 ). During CON, there was greater glycogen depletion in the type I fibres compared with type II (0.08 (0.04) vs 0.02 (0.01) optical density (OD) units; p&lt;0.05), while during VAR, there was greater glycogen depletion in the type II fibres compared with type I (0.06 (0.03) vs 0.03 (0.02) OD; p&lt;0.05). The variation in muscle glycogen depletion patterns was not associated with the detriment in running economy, which was not significantly different between conditions (52.1 vs 52.8 ml kg −1 min −1 ). There was a strong correlation between total muscle glycogen depletion and the change in running Vo 2 (r = 0.73, p&lt;0.05) when the data from both trials were combined. There was also a negative correlation between type I fibre percentage and glycogen depletion within type II fibres during CON (r = −0.85, p&lt;0.05). The results demonstrate that the decrease in running economy, subsequent to 60 minutes of cycling, is not affected by the cycling strategy employed. While different glycogen depletion patterns in the type I and II fibres were observed between conditions, total glycogen depletion may be more important to subsequent running economy. The percentage of type I fibres was associated with the glycogen depletion pattern during constant load, but not variable-intensity exercise.
Mechanism of Particulate Carrier Reactions: V. ADSORPTION OF HUMAN GAMMA GLOBULIN TO 0{middle dot}2 MICRON DIAMETER LATEX PARTICLES AND THEIR AGGLUTINATION BY RHEUMATOID FACTOR
Authors: Jacques M. Singer, Irwin Oreskes, Ferenc Hutterer, Jerome Ernst
Journal: Annals of the Rheumatic Diseases (1963)
UK heroin deaths prompt international alert
Authors: B. Christie
Journal: BMJ (2000)

A new type of infective agent linked to contaminated heroin supplies might have caused the deaths of 22 drug users in Scotland and Ireland. Since the first case was reported on 9 May, some 46people have been infected by the unidentified illness, which is being investigated by an international collaboration of public health analysts.

Screening for known causes of infection has failed to find a common source, and doctors fear that they are facing something entirely new. The pattern of infection, which has so far produced 31 cases and 14 deaths in Glasgow, seems identical to the 15 cases and eight fatalities reported in Dublin.

Dr Laurence Gruer, a Glasgow public health consultant who is coordinating the …
Do the treatment with glucocorticoids and/or the disease itself drive the impairment in glucose metabolism in patients with rheumatoid arthritis?
Authors: F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2011)

Opinions on the value of glucocorticoids (GCs) have fluctuated between euphoric acceptance and outright rejection. This ambivalence in opinions arose because of their important clinical effects, on one hand, and their potential risks, on the other hand.1 2 It seems, however, that these important drugs have now found their correct place in rheumatology (and other special areas in medicine). The current view on these drugs is that they are indispensable; however, they should be administered as much as necessary but as little as possible.

Without any doubt, GCs at higher dosages are needed to terminate flares and/or to reduce the activity of rheumatic diseases. However, this ‘emergency’ usage represents only one option for successfully administering these drugs since many patients are more or less continuously treated with ‘maintenance treatment’.

For example, when looking at rheumatoid arthritis (RA), it is obvious that, very often, lower dosages of GCs are given in combination with conventional or biological disease-modifying anti-rheumatic drugs (DMARDs) (and, of course, other drugs such as non-steroidal anti-inflammatory drugs or analgesics). This therapeutic approach has the following rationale: a sensible combination of drugs with different modes of action ideally results in additive or even synergistic effects, while potential adverse effects remain at a level associated with the dose of each component. For GC treatment, this means that the more effective the treatment is with DMARDs, the lower can be the GC dosages. Consequently, less pronounced adverse effects are induced by these drugs (figure 1).



Figure 1 
Drug combination in rheumatoid arthritis treatment. A sensible combination of drugs with different modes of action ideally results in additive or even synergistic effects, while potential adverse effects remain at a level associated with the dose of each component.



Given the widespread and successful usage of biological DMARDs, what does this mean in terms …
Additional variant of type I von willebrand disease
Authors: S. Tavori, I. Tatarsky
Journal: American Journal of Hematology (1987)

We introduce a family with a von Willebrand subgroup that has not been described before. All of the eight subjects examined had normal levels of factor VIII coagulant activity (FVIII:C), a moderate reduction in the level of von Willebrand factor antigen (VWF:Ag), which resulted in a high FVIII:C/VWF:Ag ratio, and normal crossed immunoelectrophoresis, with normal multimeric pattern. The ristocetin cofactor in plasma and platelets was very low. Bleeding time was prolonged in two subjects without clearcut linkage to laboratory findings. In addition, an abnormality of platelet aggregation in response to ADP was observed: a decreased initial response was followed by marked disaggregation.
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Authors: Patrick Therasse, Susan G. Arbuck, Elizabeth A. Eisenhauer, Jantien Wanders, Richard S. Kaplan, Larry Rubinstein, Jaap Verweij, Martine Van Glabbeke, Allan T. van Oosterom, Michaele C. Christian, Steve G. Gwyther
Journal: JNCI Journal of the National Cancer Institute (2000)

Anticancer cytotoxic agents go through a process by which their antitumor activity-on the basis of the amount of tumor shrinkage they could generate-has been investigated. In the late 1970s, the International Union Against Cancer and the World Health Organization introduced specific criteria for the codification of tumor response evaluation. In 1994, several organizations involved in clinical research combined forces to tackle the review of these criteria on the basis of the experience and knowledge acquired since then. After several years of intensive discussions, a new set of guidelines is ready that will supersede the former criteria. In parallel to this initiative, one of the participating groups developed a model by which response rates could be derived from unidimensional measurement of tumor lesions instead of the usual bidimensional approach. This new concept has been largely validated by the Response Evaluation Criteria in Solid Tumors Group and integrated into the present guidelines. This special article also provides some philosophic background to clarify the various purposes of response evaluation. It proposes a model by which a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment. Methods of assessing tumor lesions are better codified, briefly within the guidelines and in more detail in Appendix I. All other aspects of response evaluation have been discussed, reviewed, and amended whenever appropriate.
International ethics harmonization and the global alliance for genomics and health
Authors: Bartha M Knoppers
Journal: Genome Medicine (2014)

On 28 January 2013, funders and researchers met to discuss how to enable rapid progress for biomedicine by lowering global barriers to responsible and secure data sharing [1].Since then, over 130 leading organizations in health care, research and disease advocacy, operating in 40 countries, have signed a letter of intent to work towards the creation of a Global Alliance for Genomics and Health (GA4GH) [2].There are three goals: to enable open standards for interoperability of technology platforms for managing and sharing genomic and clinical data, to provide guidelines and harmonized procedures for privacy and ethics internationally, and to engage stakeholders to encourage responsible sharing of data and of methods.After the mapping and sequencing of the human genome, today's challenge is the integration of genomics data with clinical data.However, interpretation of individual sequences for genomic medicine requires an evidence base of secure data sharing within a framework of core principles.The GA4GH core principles are as follows: respect -protecting secure data sharing and privacy preferences of participants; transparency -ensuring open governance and operations; accountability -promoting best practices in technology, ethics and outreach; inclusivitypartnering and building trust among stakeholders; collaboration -sharing information to advance human health; innovation -developing an ecosystem that accelerates progress; agility -acting swiftly to benefit those with disease.The vision of the GA4GH then is to promote and facilitate the exchange of extensive data on genomic sequences, including clinical annotations, to accelerate progress in genomic medicine, such as for cancer outcomes and targeted therapy, inherited pediatric diseases, other common non-communicable diseases, infectious diseases, and drug responses.In this short paper, we will focus on the international ethics harmonization challenges that the GA4GH faces.
Goals of Inpatient Treatment for Psychiatric Disorders
Authors: Steven S. Sharfstein
Journal: Annual Review of Medicine (2008)

The purpose of the psychiatric hospital changed dramatically during the twentieth century. Formerly the primary location for psychiatric treatment, the hospital now plays a more circumscribed role within a community-based system of care. Crisis stabilization, safety, and a focus on rapid discharge are the critical components of the acute inpatient stay. Subspecialized units focus on geriatrics, children, adolescents, dual diagnosis (substance abuse and mental illness), trauma disorders, eating disorders, and forensics. When integrated with the general medical system and a comprehensive base of community-delivered day treatment, residential sevices, and outpatient services, psychiatric hospitalization is a humane alternative to long-term institutional care.
Oncolytic Adenovirus ICOVIR-7 in Patients with Advanced and Refractory Solid Tumors
Authors: Petri Nokisalmi, Sari Pesonen, Sophie Escutenaire, Merja Särkioja, Mari Raki, Vincenzo Cerullo, Leena Laasonen, Ramon Alemany, Juan Rojas, Manel Cascallo, Kilian Guse, Maria Rajecki, Lotta Kangasniemi, Elina Haavisto, Aila Karioja-Kallio, Päivi Hannuksela, Minna Oksanen, Anna Kanerva, Timo Joensuu, Laura Ahtiainen, Akseli Hemminki
Journal: Clinical Cancer Research (2010)

Twenty-one patients with cancer were treated with a single round of oncolytic adenovirus ICOVIR-7.ICOVIR-7 features an RGD-4C modification of the fiber HI-loop of serotype 5 adenovirus for enhanced entry into tumor cells. Tumor selectivity is mediated by an insulator, a modified E2F promoter, and a Rb-binding site deletion of E1A, whereas replication is optimized with E2F binding hairpins and a Kozak sequence. ICOVIR-7 doses ranged from 2 x 10(10) to 1 x 10(12) viral particles. All patients had advanced and metastatic solid tumors refractory to standard therapies.ICOVIR-7 treatment was well tolerated with mild to moderate fever, fatigue, elevated liver transaminases, chills, and hyponatremia. One patient had grade 3 anemia but no other serious side effects were seen. At baseline, 9 of 21 of patients had neutralizing antibody titers against the ICOVIR-7 capsid. Treatment resulted in neutralizing antibody titer induction within 4 weeks in 16 of 18 patients. No elevations of serum proinflammatory cytokine levels were detected. Viral genomes were detected in the circulation in 18 of 21 of patients after injection and 7 of 15 of the samples were positive 2 to 4 weeks later suggesting viral replication.Overall, objective evidence of antitumor activity was seen in 9 of 17 evaluable patients. In radiological analyses, 5 of 12 evaluable patients had stabilization or reduction in tumor size. These consisted of one partial response, two minor responses and two cases of stable disease, all occurring in patients who had progressive disease before treatment. In summary, ICOVIR-7 treatment is apparently safe, resulting in anticancer activity, and is therefore promising for further clinical testing.
Phosphatase and Tensin Homologue Deleted on Chromosome 10 Deficiency Accelerates Tumor Induction in a Mouse Model of ErbB-2 Mammary Tumorigenesis
Authors: Nathalie Dourdin, Babette Schade, Robert Lesurf, Michael Hallett, Robert J. Munn, Robert D. Cardiff, William J. Muller
Journal: Cancer Research (2008)

Loss of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and amplification or elevated expression of ErbB-2 are both involved in human breast cancer. To directly test the importance of these genetic events in mammary tumorigenesis, we have assessed whether mammary-specific disruption of PTEN could cooperate with activation of ErbB-2. Transgenic mice expressing ErbB-2 under the transcriptional control of its endogenous promoter (ErbB-2(KI)) were interbred with mice carrying conditional PTEN alleles and an MMTV/Cre transgene. Loss of one or both PTEN alleles resulted in a dramatic acceleration of mammary tumor onset and an increased occurrence of lung metastases in the ErbB-2(KI) strain. Tumor progression in PTEN-deficient/ErbB-2(KI) strains was associated with elevated ErbB-2 protein levels, which were not due to ErbB-2 amplification or to a dramatic increase in ErbB-2 transcripts. Moreover, the PTEN-deficient/ErbB-2(KI)-derived mouse mammary tumors display striking morphologic heterogeneity in comparison with the homogeneous pathology of the ErbB-2(KI) parental strain. Therefore, inactivation of PTEN would not only have a dramatic effect on ErbB-2-induced mammary tumorigenesis but would also lead to the formation of mammary tumors that, in part, display pathologic and molecular features associated with the basal-like subtype of primary human breast cancer.
Venlafaxine HCl in the treatment of painful peripheral diabetic neuropathy.
Authors: J A Kiayias, E D Vlachou, E Lakka-Papadodima
Journal: Diabetes Care (2000)

In a recent letter by Davis and Smith (1), venlafaxine HCl was reported to be effective in the symptomatic treatment of patients with painful diabetic neuropathy. This observation is in accordance with a similar finding made by us. We administered venlafaxine HCl in 8 patients who had unremitting painful peripheral diabetic neuropathy that did not respond to conventional analgesia. All patients had type 2 diabetes and were of Greek origin. The patients’ ages ranged from 49 to 80 years, and their duration of diabetes ranged from 6 to 21 years. Of these patients, 5 were men and 3 were women; 5 of the patients were being treated with oral antidiabetic agents, and 3 were on treatment with insulin. The glycemic control of each patient was good (mean HbA1c value 7.2 ± 1.2%).
STUDIES ON THE COMMON COLD
Authors: Yale Kneeland
Journal: The Journal of Experimental Medicine (1930)

1. The upper respiratory tract is sterile at birth. 2. In the first 2 weeks of life the infant acquires a basal flora comparable to that of adults except that the potential pathogens are absent. 3. During the ensuing months the potential pathogens may appear without giving rise to symptoms and by 8 months the infant's flora is entirely comparable to the adult's. 4. There is no evidence of a specific bacterial incitant for the first colds of infancy. 5. In infants with recurrent colds, secondary infection of the nose with pneumococci or B. pfeifferi probably plays a part.
Tracing the development of single memory-lineage B cells in a highly defined immune response.
Authors: A H Liu, P K Jena, L J Wysocki
Journal: The Journal of Experimental Medicine (1996)

To study the development of B lymphocyte memory, we identified and isolated splenic B cells expressing a highly defined antibody variable region that constitutes a reproducible and predominant component of the memory antibody response to p-azophenylarsonate (Ars). Isolation was achieved during the primary immune response by surface staining and flow cytometry using a specific anti-idiotypic antibody called E4, which recognizes this canonical V region, encoded by one set of V gene segments. The isolated E4+ cells displayed all of the phenotypic characteristics of germinal center centrocytes, including a low level of surface Ig, a lack of surface IgD, a high level of receptor for peanut agglutinin, and expression of mutated antibody V genes. E4+ B cells were first detected in the spleen 7-8 d after primary immunization, reached peak numbers from days 10-13, and waned by day 16. Surprisingly, at their peak, E4+ cells comprised only 40,000 of all splenocytes, and half of these failed to bind Ars. Using this number, we estimate the total number of Ars-specific memory-lineage cells in the spleen to be no more than 50,000 (0.1%) at any one time, and presumably far fewer that are committed to the memory pool. Chromosomal copies of rearranged V genes from single E4+ cells were amplified by nested PCR, and the amplified products were sequenced directly without cloning, using standardized conditions that disclose virtually no Taq polymerase errors. V gene sequence analyses of E4+ cells isolated from single mice confirmed their canonical nature and revealed that they were derived from few precursors. In the average mouse, the E4+ pool was derived from fewer than five canonical precursors. Somatic mutations were found within the V genes of almost all cell isolates. At day 13, a significant fraction of E4+ cells had mutations known to increase antibody affinity for Ars, suggesting they were products of at least one cycle of post-mutational antigen-driven selection. However, the lack of shared mutations by clonally related cells indicated that the selective expansion of mutant subclones typical of memory responses had not yet taken place. This was supported by the observation that half of the E4+ cells failed to bind Ars. Collectively, our results indicate that the memory compartment is a highly selected entity, even at relatively early stages of the primary immune response when somatic mutation and clonal selection are still in progress. If germinal centers are the source of memory B cells, our data suggest that B cell memory may be derived from only a small fraction of all germinal centers.
Microparticles From Ischemic Muscle Promotes Postnatal Vasculogenesis
Authors: Aurelie S. Leroyer, Téni G. Ebrahimian, Clément Cochain, Alice Récalde, Olivier Blanc-Brude, Barend Mees, José Vilar, Alain Tedgui, Bernard I. Levy, Giovanna Chimini, Chantal M. Boulanger, Jean-Sébastien Silvestre
Journal: Circulation (2009)

We hypothesized that microparticles (MPs) released after ischemia are endogenous signals leading to postischemic vasculogenesis.MPs from mice ischemic hind-limb muscle were detected by electron microscopy 48 hours after unilateral femoral artery ligation as vesicles of 0.1- to 1-microm diameter. After isolation by sequential centrifugation, flow cytometry analyses showed that the annexin V(+) MP concentration was 3.5-fold higher in ischemic calves than control muscles (1392+/-406 versus 394+/-180 annexin V(+) MPs per 1 mg; P<0.001) and came mainly from endothelial cells (71% of MPs are CD(144+)). MPs isolated from ischemic muscles induced more potent in vitro bone marrow-mononuclear cell (BM-MNC) differentiation into cells with endothelial phenotype than those isolated from control muscles. MPs isolated from atherosclerotic plaques were ineffective, whereas those isolated from apoptotic or interleukin-1beta-activated endothelial cells also promoted BM-MNC differentiation. Interestingly, MPs from ischemic muscles produced more reactive oxygen species and expressed significantly higher levels of NADPH oxidase p47 (6-fold; P<0.05) and p67 subunits (16-fold; P<0.001) than controls, whereas gp91 subunit expression was unchanged. BM-MNC differentiation was reduced by 2-fold with MPs isolated from gp91-deficient animals compared with wild-type mice (P<0.05). MP effects on postischemic revascularization were then examined in an ischemic hind-limb model. MPs isolated from ischemic muscles were injected into ischemic legs in parallel with venous injection of BM-MNCs. MPs increased the proangiogenic effect of BM-MNC transplantation, and this effect was blunted by gp91 deficiency. In parallel, BM-MNC proangiogenic potential also was reduced in ABCA1 knockout mice with impaired vesiculation.MPs produced during tissue ischemia stimulate progenitor cell differentiation and subsequently promote postnatal neovascularization.
Incidence and aetiology of eosinophilic pleural effusion
Authors: R. Krenke, J. Nasilowski, P. Korczynski, K. Gorska, T. Przybylowski, R. Chazan, R. W. Light
Journal: European Respiratory Journal (2009)

Although eosinophilic pleural effusion (EPE) has been a subject of numerous studies, its clinical significance still remains unclear. The aim of our study was to evaluate: 1) the relative incidence and aetiology of EPE; 2) the predictors of malignancy in patients with EPE; and 3) the relationship between repeated thoracentesis and pleural fluid eosinophilia. A retrospective analysis of 2,205 pleural fluid samples from 1,868 patients treated between 1995 and 2007 was performed. We identified 135 patients with EPE (7.2% of all patients with pleural effusion) and 153 EPE samples. The most common condition associated with EPE was malignancy (34.8%) followed by infectious (19.2%), unknown (14.1%), post-traumatic (8.9%) and miscellaneous (23.0%) pleural effusions. The incidence of malignancy was significantly higher in patients with a lower (< or =40%) pleural fluid eosinophil percentage. 40 patients with EPE underwent a second thoracentesis. In 16, eosinophilia was present in both pleural fluid samples, 14 revealed pleural fluid eosinophilia only after the second thoracentesis and 10 had eosinophilia only in the first pleural fluid sample. Pleural fluid eosinophilia should not be regarded as a predictor of nonmalignant aetiology. Probability of malignancy is lower in effusions with a high eosinophil percentage. The incidence of EPE in patients undergoing second thoracentesis is not different to that found during the first thoracentesis.