tbuckley/cabot-search huggingface dataset:
Acupuncture applied as a sensory discrimination training tool decreases movement-related pain in patients with chronic low back pain more than acupuncture alone: a randomised cross-over experiment
Authors: Benedict Martin Wand, Sam Abbaszadeh, Anne Julia Smith, Mark Jon Catley, G Lorimer Moseley
Journal: British Journal of Sports Medicine (2013)

Background High-quality clinical evidence suggests that although acupuncture appears superior to usual care in the management of chronic low back pain, there is little meaningful difference between true and sham acupuncture. This suggests that the benefits of acupuncture are mediated by the placebo response. An alternative explanation is that sham acupuncture is an active treatment and shares a mechanism of action with traditionally applied acupuncture. One plausible candidate for this mechanism is improvement in self-perception mediated through the sensory discrimination-like qualities of acupuncture. We aimed to compare the effects of acupuncture with a sensory discrimination training component to acupuncture without. Methods 25 people with chronic low back pain were enroled in a randomised cross-over experiment. We compared the effect of acupuncture delivered when sensory discrimination is optimised to acupuncture delivered when it is not, on movement-related back pain immediately after each intervention. Results We found that the average pain intensity after participants had received acupuncture with sensory discrimination training (2.8±2.5) was less than when they received acupuncture without sensory discrimination training (3.6±2.0). This difference was statistically significant (after adjustment; mean difference=−0.8, 95% CI −1.4 to −0.3; p=0.011). Conclusions Our findings are consistent with the idea that acupuncture may offer specific benefit that is not dependent on precisely where the needles are inserted so much as that the patient attends to where they are inserted. If so, the location of the needles might be better focused on the painful area and the need for penetration of the skin may be mitigated.
Rituximab in the treatment of refractory pulmonary sarcoidosis
Authors: Nadera J. Sweiss, Elyse E. Lower, Mehdi Mirsaeidi, Steven Dudek, Joe G.N. Garcia, David Perkins, Patricia W. Finn, Robert P. Baughman
Journal: European Respiratory Journal (2014)

To the Editor: 

Sarcoidosis is a chronic disease characterised by granulomatous depositions that can occur in virtually any organ system [1]. Currently, there is no US Food and Drug Administration (FDA)-approved therapy for sarcoidosis; however, corticosteroids have proven efficacious and are a commonly used treatment [2]. In patients with chronic or pulmonary disease who do not respond to corticosteroids, or in whom steroid use is contraindicated, agents such as methotrexate, azathioprine and tumour necrosis factor (TNF)-α antagonists may be effective [3, 4]. However, a need persists for patients who fail to respond to current options.

Sarcoidosis is a T-cell-mediated disease; however, humoral mechanisms may play a role in its pathogenesis [5]. Sarcoidosis is often associated with hypergammaglobulinaemia, autoantibody production and circulating immune complexes [6].

B-cell-targeted therapies have shown positive results in many T-cell-mediated autoimmune diseases. Rituximab is a chimeric monoclonal antibody that causes depletion of CD20+ B-cells [7]. Rituximab is FDA approved for the treatment of rheumatoid arthritis, granulomatosis with polyangiitis (Wegener’s) and microscopic polyangiitis, and is also being studied in Sjogren’s syndrome, systemic lupus erythematosus and vasculitis [8]. There have been case reports of the effectiveness of rituximab for sarcoidosis [9–11]. Given the evidence for humoral involvement in sarcoidosis pathogenesis, this study sought to evaluate the utility of B-cell depletion using rituximab in patients with refractory pulmonary sarcoidosis.

This was a prospective, open-label, phase I/II trial. The study was approved by the …
Activity of megestrol acetate in postmenopausal women with advanced breast cancer after nonsteroidal aromatase inhibitor failure: a phase II trial
Authors: J. Bines, R. Dienstmann, R.M. Obadia, L.G.P. Branco, D.C. Quintella, T.M. Castro, P.G. Camacho, F.A. Soares, M.E.F. Costa
Journal: Annals of Oncology (2014)
Serine proteases: new players in diarrhoea-predominant irritable bowel syndrome
Authors: G. Barbara, C. Cremon
Journal: Gut (2008)

The classical scenario depicting irritable bowel syndrome (IBS) as a disturbance of the psychological sphere, accompanied by gut sensory and motor dysfunction, is being enriched by the identification of previously unrecognised peripherally acting molecular factors.

The relatively recent identification that IBS can be triggered in previously healthy individuals by a bout of infectious gastroenteritis (ie, post-infectious IBS) is a clear paradigm of the participation of biological factors in the pathogenesis of IBS.1 Abnormal metabolism of the important gut neurotransmitter serotonin (5-HT), tissue immune activation, increased mucosal permeability and changes in gut microbiota are other examples of the recent discoveries obtained by application of a molecular approach to IBS research.2 The identified cellular and molecular factors have been found to impact on the sensory and motor apparatus of the gut and, for certain aspects, they were associated with patients’ symptoms. For example, activated mast cells in proximity to colonic nerves correlated with abdominal pain in patients with IBS.3 Furthermore, application of extracts derived from colonic mucosal biopsies of IBS patients, but not healthy controls, to the gut of naive murine laboratory animals evoked increased activation of pain-related visceral pathways4 and an “IBS-like” visceral hyperalgesia.5

Sceptical observers would argue that such subtle abnormalities could hardly explain the complexity and protean manifestations of IBS symptoms. Indeed, “stress-related” factors continue to be important players in …
Natural Killer Cells in Pulmonary Arterial Hypertension
Authors: Philipp M. Lepper, Robert Bals, Heinrike Wilkens
Journal: Circulation (2012)

P ulmonary arterial hypertension (PAH) is a progressive disorder of the pulmonary vasculature characterized by the constriction of precapillary pulmonary arteries, leading to sustained elevated pressure in pulmonary vessels.The chronic strain and then failure of the right heart leads to significant morbidity and mortality in affected patients.In untreated patients the prognosis can be as poor as in patients with malignancies.
Inter- and intraindividual variation in pressure-volume relations of the rectum in normal subjects and patients with the irritable bowel syndrome.
Authors: G P Kendall, D G Thompson, S J Day, J E Lennard-Jones
Journal: Gut (1990)

The relation between intrarectal volume and pressure during increasing rectal distension by a latex balloon were studied on repeated occasions in 10 healthy adult volunteers to define variations within and between individuals. A wide intersubject variation in the maximum tolerable volume (58-908 ml) and pressure (12.2-108.8 cm H2O) at this end point was seen, and these two values were correlated (r = 0.78). Intrasubject variation in maximum tolerable volume also occurred which was related to study order and progressively reduced with repeated study. In 26 unselected patients with pain predominant irritable bowel syndrome similar intersubject variation was noted and virtually all patients data fell within the calculated 95% confidence limits of the normal individuals. Differentiation between patients and normal subjects was not possible from knowledge of rectal responses. These noticeable inter- and intrasubject variations in rectal responses to distension need to be considered whenever similar techniques are proposed for use in the study of rectal disease or of rectal response to treatment.
Estimates of the impact of diabetes on the incidence of pulmonary tuberculosis in different ethnic groups in England
Authors: C. Walker, N. Unwin
Journal: Thorax (2010)

There is good evidence that diabetes is a risk factor for pulmonary tuberculosis. In England, the rates of both diabetes and tuberculosis vary markedly by ethnic group.To estimate the proportion of incident cases of pulmonary tuberculosis attributable to diabetes (population attributable fraction, PAF) for Asian, black and white men and women aged > or = 15 years in England.An epidemiological model was constructed using data on the incidence of tuberculosis, the prevalence of diabetes, the population structure for 2005 and the age-specific relative risk of tuberculosis associated with diabetes from a large cohort study.The estimated PAF of diabetes for pulmonary tuberculosis is highest for Asian men (19.6%, 95% CI 10.9% to 33.1%) and women (14.2%, 95% CI 7.1% to 26.5%). The PAF for all ages is similar in white and black men (6.9%, 95% CI 3.1% to 12.4% and 7.4%, 95% CI 4.6% to 12.9%, respectively) and women (8.2%, 95% CI 3.0% to 15.6% and 8.9%, 95% CI 5.3% to 15.6%, respectively). The similarity of these overall figures, despite a higher prevalence of diabetes in the black population, reflects a much younger mean age of pulmonary tuberculosis in the black population. Overall, of 3461 new cases of pulmonary tuberculosis in England in 2005, 384 (202-780) were estimated to be attributable to diabetes.Given the nature of the data available, considerable uncertainty surrounds these estimates. Nonetheless, they highlight the potential importance of diabetes as a risk factor for pulmonary tuberculosis, particularly in groups at high risk of both diseases. Further research to examine the implications of these findings for tuberculosis control is urgently needed.
Anticoagulants and mitral valvotomy: a nine-year survey.
Authors: S F Stephenson
Journal: Thorax (1966)

Systemic embolism, occurring during either the operation or in the post-operative period, remains a serious complication of mitral valvotomy.It causes many deaths and those who survive it may suffer a crippling permanent disability.Since 1955 anticoagulants have been widely used at the Hill Top Hospital, Bromsgrove, for the purpose of preventing clot formation and subsequent dis- semination at operation, and the results of this therapy form the basis of this study. INCIDENCE AND CAUSATIONSystemic emboli associated with mitral valvotomy occur in about 5% of patients and carry a mortality of about 2%, which is nearly half the total mortality of this operation.At least two-thirds of all emboli affect the cerebral circulation.Table I shows the incidence of embolism in various published series; the figures collected for the TABLE I INCIDENCE OF EMBOLISM COMPLICATING MITRAL VALVOTOMY
Boric Acid Preservation of Urine Samples
Authors: I. A. Porter, J. Brodie
Journal: BMJ (1969)

Comparison of the results of bacteriological culture and microscopic examination of urine samples transported over a distance by the dip-inoculum transport medium, ice-box, and boric acid preservation with "natural" urine specimens showed that the last, in a final concentration of 1.8%, gives satisfactory preservation.
781 IDENTIFICATION OF HEPATITIS C VIRUS (HCV) GLYCOPROTEIN E2 DOMAINS AND RESIDUES RESPONSIBLE FOR INTERACTION WITH HEPARAN SULFATE
Authors: J. Dragun, G. Koutsoudakis, S. Perez-del-Pulgar, M. Coto-Llerena, L. Mensa, G. Crespo, M. Navasa, X. Forns
Journal: Journal of Hepatology (2011)
Renal Transfer of Genetically Engineered Cells
Authors: MASANORI KITAMURA
Journal: Journal of the American Society of Nephrology (2000)

For many years, ex vivo gene transfer has been used for genetic manipulation of various organs. In the kidney, ex vivo gene transfer was reported using mesangial cells and macrophages. In rats, cultured cells injected into the renal artery are accumulated selectively in the glomerulus. With this approach, it is possible to transfer genetically engineered cells to normal and diseased glomeruli. The transfer of genetically engineered cells to glomeruli can be used for several purposes. With the use of resident glomerular cells engineered in vitro, it is possible to examine how the cells that overexpress certain genes behave differently in normal and diseased glomeruli. Both gain-of-function and loss-of-function strategies are useful for this purpose. For the latter, stable expression of antisense cDNA, ribosomes, or dominant-negative mutants is available. By transfer of engineered cells producing secretory, recombinant proteins, it is possible to modify glomerular microenvironment in vivo. Transfer of genes encoding therapeutically relevant molecules could be useful for therapeutic intervention. Transfer of engineered leukocytes to the glomerulus also allows investigation of cross talk between leukocytes and resident cells. Transfer of stimulated leukocytes is useful for investigation of the pathologic actions of infiltrating cells on glomerular structure and function. Leukocytes in which certain gene functions are selectively reinforced or deleted would be useful for elucidation of the exact functions of leukocyte-associated genes in glomerular diseases. This article summarizes current experience with the adoptive transfer of engineered cells to the glomerulus for investigation of and therapy for glomerular diseases.
Evolutionary Lineages of RT1.Ba in the Australian Rattus
Authors: J. M. Seddon, P. R. Baverstock
Journal: Molecular Biology and Evolution (2000)

In this study, the evolutionary history of the variable second exon of RT1.Ba and its adjoining intron b are compared across a number of species and subspecies of the Australian Rattus. Three lineages are identified in the second intron across a range of Rattus species. Two of these lineages, separated by the insertion of a probable rodent short interspersed nucleotide element and by point mutations outside the indel region, are both found in each of the major clades of the endemic Australian Rattus. This pattern of ancestral polymorphism is reflected in the adjoining exon 2 sequences, although phylogenetic constraints confirm that the clustering is not identical to that of the associated intron sequences. In addition, the coding sequences show evidence of the retention of ancestral polymorphism, with identical exon sequences found in two divergent species, and some indication of gene conversion detected for the exon sequences.
Isocitrate Dehydrogenase 1 and 2 Mutations in Cancer: Alterations at a Crossroads of Cellular Metabolism
Authors: Z. J. Reitman, H. Yan
Journal: JNCI Journal of the National Cancer Institute (2010)

Dysregulation of metabolism is a common phenomenon in cancer cells. The NADP + -dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) function at a crossroads of cellular metabolism in lipid synthesis, cellular defense against oxidative stress, oxidative respiration, and oxygen-sensing signal transduction. We review the normal functions of the encoded enzymes, frequent mutations of IDH1 and IDH2 recently found in human cancers, and possible roles for the mutated enzymes in human disease. IDH1 and IDH2 mutations occur frequently in some types of World Health Organization grades 2–4 gliomas and in acute myeloid leukemias with normal karyotype. IDH1 and IDH2 mutations are remarkably specific to codons that encode conserved functionally important arginines in the active site of each enzyme. To date, all IDH1 mutations have been identified at the Arg132 codon. Mutations in IDH2 have been identified at the Arg140 codon, as well as at Arg172, which is aligned with IDH1 Arg132. IDH1 and IDH2 mutations are usually heterozygous in cancer, and they appear to confer a neomorphic enzyme activity for the enzymes to catalyze the production of D -2-hydroxyglutarate. Study of alterations in these metabolic enzymes may provide insights into the metabolism of cancer cells and uncover novel avenues for development of anticancer therapeutics.
Updates in non-small cell lung cancer - insights from the 2009 45th annual meeting of the American Society of Clinical Oncology
Authors: Hamid R Mirshahidi, Chung T Hsueh
Journal: Journal of Hematology & Oncology (2010)

We have reviewed the pivotal presentations in non-small cell lung cancer (NSCLC) from the 2009 annual meeting of the American Society of Clinical Oncology. We have discussed the scientific data, the impact on standards of care, and ongoing clinical trials. In patients with early-stage NSCLC, there is still no data to support the superiority of either neoadjuvant or adjuvant chemotherapy. However, adjuvant cisplatin-based chemotherapy has sustained the survival benefits after median follow-up of more than 9 years. The first-line treatment with inhibitors of epidermal growth factor receptor (EGFR) could be considered for the treatment of EGFR mutated patients with metastatic disease. Several maintenance studies with cytotoxic or biological agents have also demonstrated promising outcomes. Finally, novel targeted agents such as inhibitors of histone deacetylase and multi-targeted tyrosine kinase inhibitor have shown promising activity in NSCLC treatment.
Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT
Authors: H.S. Hochster, A. Grothey, L. Hart, K. Rowland, R. Ansari, S. Alberts, N. Chowhan, R.K. Ramanathan, M. Keaton, J.D. Hainsworth, B.H. Childs
Journal: Annals of Oncology (2014)
Regenerative Medicine: Bio‐electrospraying and Cell Electrospinning: Progress and Opportunities for Basic Biology and Clinical Sciences (Adv. Healthcare Mater. 1/2012)
Authors: Denis Poncelet, Paul de Vos, Nicolai Suter, Suwan N. Jayasinghe
Journal: Advanced Healthcare Materials (2012)

Bio-electrosprays and cell electrospinning have recently been shown benign for directly handling living cells and whole organisms in both in vitro and in vivo testing. In their Progress Report on page 27, Suwan N. Jayasinghe and coworkers review these approaches, which are the subjects of pre-clinical studies that validate new technologies on model organisms such as Xenopus tropicalis, shown in the image. (Image credits: T. J. Geach, L. B. Zimmerman, and S. N. Jayasinghe.)
Nasal nitric oxide and nitric oxide synthase expression in primary ciliary dyskinesia
Authors: M. Pifferi, A. Bush, F. Maggi, A. Michelucci, V. Ricci, M.E. Conidi, A.M. Cangiotti, A. Bodini, P. Simi, P. Macchia, A.L. Boner
Journal: European Respiratory Journal (2011)

No study has evaluated the correlation between different expression of nitric oxide synthase (NOS) isoforms in nasal epithelial cells and nasal NO (nNO) level in primary ciliary dyskinesia (PCD). Gene expression of endothelial (NOS3) and inducible NOS (NOS2) and their correlation with nNO level, ciliary function and morphology were studied in patients with PCD or secondary ciliary dyskinesia (SCD). NOS3 gene polymorphisms were studied in blood leukocytes. A total of 212 subjects were studied (48 with PCD, 161 with SCD and three normal subjects). nNO level correlated with mean ciliary beat frequency (p = 0.044; r = 0.174). The lower the nNO level the higher was the percentage of immotile cilia (p<0.001; r = -0.375). A significant positive correlation between NOS2 gene expression and nNO levels was demonstrated in all children (p = 0.001; r = 0.428), and this correlation was confirmed in patients with PCD (p = 0.019; r = 0.484). NOS2 gene expression was lower in PCD than in SCD (p = 0.04). The NOS3 isoform correlated with missing central microtubules (p = 0.048; r = 0.447). nNO levels were higher in PCD subjects with the NOS3 thymidine 894 mutation, and this was associated with a higher ciliary beat frequency (p = 0.045). These results demonstrate a relationship between nNO level, NOS mRNA expression and ciliary beat frequency.
Magnetic Resonance Imaging of Cerebral Lesions in Patients with the Sjögren Syndrome
Authors: ELAINE L. ALEXANDER
Journal: Annals of Internal Medicine (1988)

Thirty-eight patients with the primary Sjögren syndrome, 16 with active neuropsychiatrie manifestations and 22 without clinical evidence of central nervous system involvement had magnetic resonance (MR) imaging. Eight patients had focal neurologic deficits (6 of these also had psychiatric or cognitive dysfunction), and 8 had psychiatric or cognitive abnormalities alone. Magnetic resonance imaging showed abnormal results in 12 of 16 (75%; 95% Cl, 48 to 93) patients with active central nervous system disease (67 focal lesions predominantly within the subcortical and periventricular white matter), and in 2 of 22 (9%; 95% Cl, 1 to 29) patients without clinical evidence of central nervous system disease (P < 0.0001). Seven of eight patients with focal neurologic deficits and 5 of 8 patients with psychiatric or cognitive dysfunction alone had abnormal results on MR imaging. Magnetic resonance imaging was more sensitive in the subgroup with focal deficits, (sensitivity, 88%; 95% Cl, 44 to 97) than computerized axial tomography or cerebral angiography. Magnetic resonance imaging detects focal cerebral lesions in patients with the Sjögren syndrome and central nervous system involvement, including patients with psychiatric and cognitive dysfunction alone.
A Myocardial Nox2 Containing NAD(P)H Oxidase Contributes to Oxidative Stress in Human Atrial Fibrillation
Authors: Young M. Kim, Tomasz J. Guzik, Yin Hua Zhang, Mei Hua Zhang, Hassan Kattach, Chandi Ratnatunga, Ravi Pillai, Keith M. Channon, Barbara Casadei
Journal: Circulation Research (2005)

Human atrial fibrillation (AF) has been associated with increased atrial oxidative stress. In animal models, inhibition of reactive oxygen species prevents atrial remodeling induced by rapid pacing, suggesting that oxidative stress may play an important role in the pathophysiology of AF. NAD(P)H oxidase is a major source of superoxide in the cardiovascular system; however, whether this enzyme contributes to atrial oxidative stress in AF remains to be elucidated. We investigated the sources of superoxide production (using inhibitors and substrates of a range of oxidases, RT-PCR, immunofluorescence, and immunoblotting) in tissue homogenates and isolated atrial myocytes from the right atrial appendage (RAA) of patients undergoing cardiac surgery (n=54 in sinus rhythm [SR] and 15 in AF). A membrane-bound gp91phox containing NAD(P)H oxidase in atrial myocytes was the main source of atrial superoxide production in SR and in AF. NADPH-stimulated superoxide release from RAA homogenates was significantly increased in patients with AF in the absence of changes in mRNA expression of the p22phox and gp91phox subunits of the NAD(P)H oxidase. In contrast with findings in SR patients, NO synthases (NOSs) contributed significantly to atrial superoxide production in fibrillating atria, suggesting that increased oxidative stress in AF may lead to NOS “uncoupling.” These findings indicate that a myocardial NAD(P)H oxidase and, to a lesser extent, dysfunctional NOS contribute significantly to superoxide production in the fibrillating human atrial myocardium and may play an important role in the atrial oxidative injury and electrophysiological remodeling observed in patients with AF.
S100A1: A Novel and Essential Molecular Component for Postischemic Angiogenesis
Authors: Betty Descamps, Paolo Madeddu, Costanza Emanueli
Journal: Circulation Research (2013)

C ritical limb ischemia is associated with significant mor- bidity and mortality.Revascularization is not always feasible or successful.Consequently, in a worryingly high percentage of patients, amputation is the only option.It is hoped that a wider understanding of the molecular mechanisms underpinning limb ischemia can help develop new and truly revolutionary therapeutic strategies.