tbuckley/cabot-search huggingface dataset:
Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade
Authors: T. Rooney, P. Roux-Lombard, D. J. Veale, O. FitzGerald, J.-M. Dayer, B. Bresnihan
Journal: Annals of the Rheumatic Diseases (2009)

Objectives To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). Methods Patients with active RA entered a randomised study of anakinra 100 mg/day, administered as monotherapy or in combination with pegsunercept 800 μg/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. Results Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFβ) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor/TGFβ, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. Conclusions Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.
Primary Ciliary Dyskinesia. Recent Advances in Diagnostics, Genetics, and Characterization of Clinical Disease
Authors: Michael R. Knowles, Leigh Anne Daniels, Stephanie D. Davis, Maimoona A. Zariwala, Margaret W. Leigh
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia that leads to oto-sino-pulmonary diseases and organ laterality defects in approximately 50% of cases. The estimated incidence of PCD is approximately 1 per 15,000 births, but the prevalence of PCD is difficult to determine, primarily because of limitations in diagnostic methods that focus on testing ciliary ultrastructure and function. Diagnostic capabilities have recently benefitted from (1) documentation of low nasal nitric oxide production in PCD and (2) discovery of biallelic mutations in multiple PCD-causing genes. The use of these complementary diagnostic approaches shows that at least 30% of patients with PCD have normal ciliary ultrastructure. More accurate identification of patients with PCD has also allowed definition of a strong clinical phenotype, which includes neonatal respiratory distress in >80% of cases, daily nasal congestion and wet cough starting soon after birth, and early development of recurrent/chronic middle-ear and sinus disease. Recent studies, using advanced imaging and pulmonary physiologic assessments, clearly demonstrate early onset of lung disease in PCD, with abnormal air flow mechanics by age 6-8 years that is similar to cystic fibrosis, and age-dependent onset of bronchiectasis. The treatment of PCD is not standardized, and there are no validated PCD-specific therapies. Most patients with PCD receive suboptimal management, which should include airway clearance, regular surveillance of pulmonary function and respiratory microbiology, and use of antibiotics targeted to pathogens. The PCD Foundation is developing a network of clinical centers, which should improve diagnosis and management of PCD.
Exercise training in heart failure: from theory to practice. A consensus document of the Heart Failure Association and the European Association for Cardiovascular Prevention and Rehabilitation
Authors: Massimo F. Piepoli, Viviane Conraads, Ugo Corrà, Kenneth Dickstein, Darrel P. Francis, Tiny Jaarsma, John McMurray, Burkert Pieske, Ewa Piotrowicz, Jean-Paul Schmid, Stefan D. Anker, Alain Cohen Solal, Gerasimos S. Filippatos, Arno W. Hoes, Stefan Gielen, Pantaleo Giannuzzi, Piotr P. Ponikowski
Journal: European Journal of Heart Failure (2011)
Orthotopic liver transplantation for incurable alveolar echinococcosis of the liver: Report of 17 cases
Authors: S. Bresson-Hadni, A. Franza, J. P. Miguet, D. A. Vuitton, D. Lenys, E. Monnet, G. Landecy, G. Paintaud, P. Rohmer, M. C. Becker, J. L. Christophe, G. Mantion, M. Gillet
Journal: Hepatology (1991)

Between 1986 and 1989, orthotopic liver transplantations were performed in our unit for 17 patients with incurable alveolar echinococcosis. Ten patients had hilar involvement (group I), and seven patients had posterior localization (five of them had chronic Budd-Chiari syndrome) (group II). The delay between diagnosis and the orthotopic liver transplantation was more than 48 mo in group Ia (six patients), less than 24 mo in group Ib (four patients) and less than 48 mo in group II. Previous operations were more common in group Ia than in group Ib and II. Five patients have died-four in group I and one in group II. The actuarial survival rate at 15 mo was 75%. Early reoperations were frequent (69%), mainly caused by rebleeding. Bacterial and fungal infections occurred only in group Ia (four cases) and group II (three cases). In eight patients (palliative group), residual foci of infected nonhepatic tissue occurred after surgery. The titer of specific antibodies decreased during the first 3 mo in all the patients but one. In patients with radical liver transplantation, the complete disappearance of specific antibodies occurred within 2 yr in four cases. In the remaining five patients, specific antibodies remained detectable, but no evidence of recurrence has been obtained up to now. In the palliative group, a peak of specific IgM occurred at 3 mo; an increase of specific IgG was observed later. The growth of residual parasitic foci was relatively slow, and all these patients remained asymptomatic with a mean follow-up of 19 mo. We conclude that orthotopic liver transplantation is feasible in incurable alveolar echinococcosis and could be proposed without delay to patients with parasitic Budd-Chiari syndrome or complicated secondary biliary cirrhosis. In the other cases, the best time to perform an orthotopic liver transplantation is more difficult to determine. Nevertheless, in the perspective of an orthotopic liver transplantation, the management of these patients has to change, and repetitive laparotomies for palliative surgical procedures have to be replaced by interventional radiology.
Analysis of Qa-1bPeptide Binding Specificity and the Capacity of Cd94/Nkg2a to Discriminate between Qa-1–Peptide Complexes
Authors: Jennifer R. Kraft, Russell E. Vance, Jan Pohl, Amy M. Martin, David H. Raulet, Peter E. Jensen
Journal: The Journal of Experimental Medicine (2000)

The major histocompatibility complex class Ib protein, Qa-1b, serves as a ligand for murine CD94/NKG2A natural killer (NK) cell inhibitory receptors. The Qa-1b peptide-binding site is predominantly occupied by a single nonameric peptide, Qa-1 determinant modifier (Qdm), derived from the leader sequence of H-2D and L molecules. Five anchor residues were identified in this study by measuring the peptide-binding affinities of substituted Qdm peptides in experiments with purified recombinant Qa-1b. A candidate peptide-binding motif was determined by sequence analysis of peptides eluted from Qa-1 that had been folded in the presence of random peptide libraries or pools of Qdm derivatives randomized at specific anchor positions. The results indicate that Qa-1b can bind a diverse repertoire of peptides but that Qdm has an optimal primary structure for binding Qa-1b. Flow cytometry experiments with Qa-1b tetramers and NK target cell lysis assays demonstrated that CD94/NKG2A discriminates between Qa-1b complexes containing peptides with substitutions at nonanchor positions P4, P5, or P8. Our findings suggest that it may be difficult for viruses to generate decoy peptides that mimic Qdm and raise the possibility that competitive replacement of Qdm with other peptides may provide a novel mechanism for activation of NK cells.
Reassessing Models of Basal Ganglia Function and Dysfunction
Authors: Alexandra B. Nelson, Anatol C. Kreitzer
Journal: Annual Review of Neuroscience (2014)

The basal ganglia are a series of interconnected subcortical nuclei. The function and dysfunction of these nuclei have been studied intensively in motor control, but more recently our knowledge of these functions has broadened to include prominent roles in cognition and affective control. This review summarizes historical models of basal ganglia function, as well as findings supporting or conflicting with these models, while emphasizing recent work in animals and humans directly testing the hypotheses generated by these models.
Hypnosis of the Deaf Mentally Ill: A Clinical Study
Authors: JOSEPH T. MARTORANO, CHARLES OESTREICHER
Journal: American Journal of Psychiatry (1966)

With the development of the first psychiatric inpatient facility for the deaf within a state mental hospital, the need for the development of new therapeutic technique for use with the deaf has been reemphasized. The paper describes the first use of hypnotic techniques devised specifically for the deaf mentally ill patient. The procedure for hypnosis and its application to 12 congenitally deaf mentally ill patients are described, and the ramifications for further development of hypnotic techniques with the deaf are briefly discussed.
Omega-3 Polyunsaturated Essential Fatty Acid Status as a Predictor of Future Suicide Risk
Authors: M. Elizabeth Sublette, Joseph R. Hibbeln, Hanga Galfalvy, Maria A. Oquendo, J. John Mann
Journal: American Journal of Psychiatry (2006)

Objective: Low levels of docosahexaenoic acid, a polyunsaturated fatty acid, and elevated ratios of omega-6/omega-3 fatty acids are associated with major depression and, possibly, suicidal behavior. Predicting risk of future suicidal behaviors by essential fatty acid status merits examination. Method: Plasma polyunsaturated fatty acid levels in phospholipids were measured in 33 medication-free depressed subjects monitored for suicide attempt over a 2-year period. Survival analysis examined the association of plasma polyunsaturated fatty acid status and pathological outcome. Results: Seven subjects attempted suicide on follow-up. A lower docosahexaenoic acid percentage of total plasma polyunsaturated fatty acids and a higher omega-6/omega-3 ratio predicted suicide attempt. Conclusions: A low docosahexaenoic acid percentage and low omega-3 proportions of lipid profile predicted risk of suicidal behavior among depressed patients over the 2-year period. If confirmed, this finding would have implications for the neurobiology of suicide and reduction of suicide risk.
Effects of Music Therapy on Anesthesia Requirements and Anxiety in Women Undergoing Ambulatory Breast Surgery for Cancer Diagnosis and Treatment: A Randomized Controlled Trial
Authors: Jaclyn Bradley Palmer, Deforia Lane, Diane Mayo, Mark Schluchter, Rosemary Leeming
Journal: Journal of Clinical Oncology (2015)

To investigate the effect of live and recorded perioperative music therapy on anesthesia requirements, anxiety levels, recovery time, and patient satisfaction in women experiencing surgery for diagnosis or treatment of breast cancer.
Neurophysiology indicates cognitive penetration of the visual system
Authors: Alexander Grunewald
Journal: Behavioral and Brain Sciences (1999)

Short-term memory, nonattentional task effects and nonspatial extraretinal representations in the visual system are signs of cognitive penetration. All of these have been found physiologically, arguing against the cognitive impenetrability of vision as a whole. Instead, parallel subcircuits in the brain, each subserving a different competency including sensory and cognitive (and in some cases motor) aspects, may have cognitively impenetrable components.
Cost effectiveness of nurse led secondary prevention clinics for coronary heart disease in primary care: follow up of a randomised controlled trial
Authors: James P Raftery, Guiqing L Yao, Peter Murchie, Neil C Campbell, Lewis D Ritchie
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To establish the cost effectiveness of nurse led secondary prevention clinics for coronary heart disease based on four years9 follow up of a randomised controlled trial. <b>Design</b> Cost effectiveness analysis. <b>Setting</b> 19 general practices in north east Scotland. <b>Participants</b> 1343 patients (673 in intervention group and 670 in control group, as originally randomised) aged under 80 years with a diagnosis of coronary heart disease but without terminal illness or dementia and not housebound. <b>Intervention</b> Nurse led clinics to promote medical and lifestyle components of secondary prevention. <b>Main outcome measures</b> Costs of clinics; overall costs to health service; and cost per life year and per quality adjusted life year (QALY) gained, expressed as incremental gain in intervention group compared with control group. <b>Results</b> The cost of the intervention (clinics and drugs) was £136 ($254; €195) per patient higher (1998-9 prices) in the intervention group, but the difference in other NHS costs, although lower for the intervention group, was not statistically significant. Overall, 28 fewer deaths occurred in the intervention group leading to a gain in mean life years per patient of 0.110 and of 0.124 QALYs. The incremental cost per life year saved was £1236 and that per QALY was £1097. <b>Conclusion</b> Nurse led clinics for the secondary prevention of coronary heart disease in primary care seem to be cost effective compared with most interventions in health care, with the main gains in life years saved.
Pharmacology and special clinical applications of low‐molecular‐weight heparins
Authors: J. Harenberg, D. L. Heene
Journal: American Journal of Hematology (1988)

Abstract In this overview, the rationale of the development of low‐molecular‐weight (LMW) heparins and their toxicological, anticoagulant, fibrinolytic, lipolytic, and protamine interactions are summarized. Clinical experiences are reviewed on the benefit of LMW heparin for anticoagulation in patients with bleeding and other complications on conventional anticoagulants and during pregnancy. It is concluded that animal experiments have demonstrated the safety of LMW heparins, that the pharmacologic profile is improved compared with normal heparin, and that the simple and safe applicability of LMW heparins gives rise to new indications for the long‐term prophylaxis of thromboembolism.
From collaboration to commissioning: developing relationships between primary health and social services
Authors: C. Glendinning, K. Rummery, R. Clarke
Journal: BMJ (1998)

Since the publication in 1989 of the white paper, Caring for People , the benefits of collaboration between primary health and social services have been emphasised—albeit with little guidance on how to achieve this. 1 2 The success of emergency initiatives to reduce pressure on hospital beds and, in future, health action zones,3 will also depend on good relationships between agencies. The recent NHS white paper also emphasises the importance of partnerships, and proposes that local authority representatives are involved in both primary care groups and health authority meetings.4

Collaboration is important, particularly since the 1993 changes in community care, because general practitioners and social services staff act as gatekeepers to other services. General practitioners control access to secondary and community health services through patient referrals. Social services departments manage funding for home care services and residential and nursing home places and control access through assessment and care management. When one professional or organisation depends on another professional or organisation to obtain services, their ability to achieve their own professional or organisational objectives is affected crucially. Thus, general practitioners depend on social services' funding of nursing home places or intensive domiciliary services to avoid admission to hospital for some patients or to support other patients after discharge home.

For many general practitioners, closer links with their social services department are a high priority. Some writers have argued that the surgery is an ideal base for social services because of the universality that characterises primary care.5 Others have suggested that general practitioners should be given an integrated budget from which they can purchase both health and social services.6 Although some studies have indicated a lack of success in achieving collaborative working, this may reflect a lack of clarity and realism about the goals and barriers associated with …
CD47 Mediates Killing of Breast Tumor Cells via Gi-Dependent Inhibition of Protein Kinase A
Authors: Partha Pratim Manna, William A. Frazier
Journal: Cancer Research (2004)

Abstract Thrombospondins (TSPs) have been implicated as antitumor and antimetastasis factors in breast cancer. Although this effect has been attributed to the antiangiogenic activity of TSPs, recent observations suggest other mechanisms may be at work. The TSP receptor CD47 (integrin-associated protein) has recently been reported to mediate a novel form of apoptosis. Here, we have studied the response of breast cancer cells to CD47 ligands TSP-1, the CD47 agonist peptide 4N1K derived from TSP-1, and the anti-CD47 monoclonal antibody 1F7. All of these ligands killed four different breast cancer cell lines. This CD47-mediated cell death did not require active caspases or Bcl-2 degradation and did not cause DNA laddering or cytochrome c release. Pertussis toxin (PTX) prevented CD47-mediated death, indicating the involvement of Giα. 4N1K dramatically reduced intracellular cAMP levels, an effect reversed with PTX. Forskolin, 8-bromo cAMP, and isobutylmethylxanthine (IBMX) all prevented CD47-mediated apoptosis, indicating the involvement of cAMP. H89 and protein kinase A (PKA) inhibitor peptide prevented rescue of breast cancer cells by PTX, 8-Br-cAMP, and forskolin, suggesting that the effects of cAMP are mediated via PKA-dependent phosphorylation events. Epidermal growth factor also inhibited CD47-induced apoptosis via a PKC-dependent but ERK-independent pathway. Thus, CD47-mediated killing of breast cancer cells occurs by a novel pathway involving regulation of cAMP levels by heterotrimeric Gi with subsequent effects mediated by PKA.
Epitopes of streptococcal M proteins shared with cardiac myosin.
Authors: J B Dale, E H Beachey
Journal: The Journal of Experimental Medicine (1985)

We present evidence that M proteins from three different serotypes of group A streptococci share epitopes with cardiac myosin. Rabbit antisera evoked by a purified fragment of type 5 M protein crossreacted with myosin, but not alpha-tropomyosin, actin, or myosin light chains. In enzyme-linked immunosorbent assays, the myosin-crossreactive antibodies were totally inhibited by type 5 M protein and partially inhibited by types 6 and 19 M proteins. The affinity-purified myosin antibodies opsonized type 5 streptococci, indicating that they were directed against protective M protein epitopes on the surface of the organisms. Immunoblot analyses demonstrated the binding of the crossreactive antibodies to myosin heavy chains. Sera from patients with acute rheumatic fever showed significantly stronger reactions with myosin than did sera from their siblings, hospitalized controls, or patients with poststreptococcal glomerulonephritis.
Persistence of Contradicted Claims in the Literature
Authors: Athina Tatsioni, Nikolaos G. Bonitsis, John P. A. Ioannidis
Journal: JAMA (2007)

Some research findings based on observational epidemiology are contradicted by randomized trials, but may nevertheless still be supported in some scientific circles.To evaluate the change over time in the content of citations for 2 highly cited epidemiological studies that proposed major cardiovascular benefits associated with vitamin E in 1993; and to understand how these benefits continued being defended in the literature, despite strong contradicting evidence from large randomized clinical trials (RCTs). To examine the generalizability of these findings, we also examined the extent of persistence of supporting citations for the highly cited and contradicted protective effects of beta-carotene on cancer and of estrogen on Alzheimer disease.For vitamin E, we sampled articles published in 1997, 2001, and 2005 (before, early, and late after publication of refuting evidence) that referenced the highly cited epidemiological studies and separately sampled articles published in 2005 and referencing the major contradicting RCT (HOPE trial). We also sampled articles published in 2006 that referenced highly cited articles proposing benefits associated with beta-carotene for cancer (published in 1981 and contradicted long ago by RCTs in 1994-1996) and estrogen for Alzheimer disease (published in 1996 and contradicted recently by RCTs in 2004).The stance of the citing articles was rated as favorable, equivocal, and unfavorable to the intervention. We also recorded the range of counterarguments raised to defend effectiveness against contradicting evidence.For the 2 vitamin E epidemiological studies, even in 2005, 50% of citing articles remained favorable. A favorable stance was independently less likely in more recent articles, specifically in articles that also cited the HOPE trial (odds ratio for 2001, 0.05 [95% confidence interval, 0.01-0.19; P < .001] and the odds ratio for 2005, 0.06 [95% confidence interval, 0.02-0.24; P < .001], as compared with 1997), and in general/internal medicine vs specialty journals. Among articles citing the HOPE trial in 2005, 41.4% were unfavorable. In 2006, 62.5% of articles referencing the highly cited article that had proposed beta-carotene and 61.7% of those referencing the highly cited article on estrogen effectiveness were still favorable; 100% and 96%, respectively, of the citations appeared in specialty journals; and citations were significantly less favorable (P = .001 and P = .009, respectively) when the major contradicting trials were also mentioned. Counterarguments defending vitamin E or estrogen included diverse selection and information biases and genuine differences across studies in participants, interventions, cointerventions, and outcomes. Favorable citations to beta-carotene, long after evidence contradicted its effectiveness, did not consider the contradicting evidence.Claims from highly cited observational studies persist and continue to be supported in the medical literature despite strong contradictory evidence from randomized trials.
Erosive papulonodular dermatosis associated with topical benzocaine: A report of two cases and evidence that granuloma gluteale, pseudoverrucous papules, and Jacquet's erosive dermatitis are a disease spectrum
Authors: Kristi J. Robson, Julie A. Maughan, Susan D. Purcell, Marta J. Petersen, Hope K. Haefner, Lori Lowe
Journal: Journal of the American Academy of Dermatology (2006)