tbuckley/cabot-search huggingface dataset:
A pilot study of interferon alfa and ribavirin combination in liver transplant recipients with recurrent hepatitis C
Authors: A. Obaid Shakil, Brendon McGuire, Jeff Crippin, Lewis Teperman, A. Jake Demetris, Hari Conjeevaram, Robert Gish, Paul Kwo, Vijayan Balan, Teresa L. Wright, Clifford Brass, Jorge Rakela
Journal: Hepatology (2002)

Although interferon alfa (IFN-α) and ribavirin are widely used in the treatment of hepatitis C, their role in the transplant recipient is unclear. We conducted a pilot study to determine the efficacy and safety of this therapy in transplant recipients with recurrent hepatitis C. Patients at least 6 months posttransplantation were treated with IFN-α 3 million units 3 times a week subcutaneously and ribavirin 800 mg daily by mouth for 48 weeks followed by ribavirin monotherapy for 24 weeks. The primary end point was sustained virologic response, and secondary end points included biochemical, virologic, and histologic responses at the end of combination treatment. Thirty-eight patients initiated therapy but 16 withdrew due to adverse effects, including 2 with myocardial infarction. Median age was 50 years; 74% were men, and 91% had genotype 1. The median interval between transplantation and enrollment was 23 months. On an intention-to-treat basis, 7 patients (18%) had a biochemical and 5 (13%) had a virologic response at the end of combination treatment. Inflammatory activity did not change, but fibrosis worsened in virologic nonresponders. Ribavirin maintenance caused a further decrease in serum alanine aminotransferase levels, but hepatitis C virus (HCV) RNA levels increased. Only 2 of the 38 patients (5%) had a sustained virologic response. Several patients required treatment with erythropoietin for anemia. In conclusion, IFN-α and ribavirin are effective in a small proportion of liver allograft recipients with recurrent hepatitis C. Adverse effects occur commonly, requiring dose reductions and treatment withdrawal.
Antiphospholipid antibodies and RA: presence of beta2GP1 independent aCL
Authors: C BONNET
Journal: Annals of the Rheumatic Diseases (2001)

abnormality of SS.However, any conclusion must await a further extensive study.Optimal thresholds of gland function were insuYciently accurate for diagnosis of SS, as they failed to discriminate between SS and controls, probably owing to diVerent degrees of dysfunction in the patients with SS and the small sample size.We noted that tracer accumulation by the parotid gland decreased in sicca syndrome, but failed to show similar changes in submandibular uptake. 9 10A decreased excretion fraction in all glands compared with normal is characteristic of sicca syndrome and not exclusive to SS as has been described. 9 10
Polymorphism at position +896 of the toll-like receptor 4 gene interferes with rapid response to treatment in rheumatoid arthritis
Authors: K Kuuliala, A Orpana, M Leirisalo-Repo, H Kautiainen, M Hurme, P Hannonen, M Korpela, T Mottonen, L Paimela, K Puolakka, A Karjalainen, H Repo
Journal: Annals of the Rheumatic Diseases (2006)

The aim of this study was to determine whether the +896 A→G substitution of the Toll-like receptor 4 (<i>TLR4</i>) gene, causing the Asp299→Gly change in the extracellular domain of TLR4, influences treatment response in recent-onset rheumatoid arthritis. 169 patients with rheumatoid arthritis were genotyped from the Finnish Rheumatoid Arthritis Combination Therapy trial, in which they were treated either with only one disease-modifying antirheumatic drug (DMARD) with or without prednisolone (single group), or with three DMARDs and prednisolone (combination group). Patients homozygotic for the wild-type +896A allele were compared with those having the polymorphic G allele in terms of early clinical response (at 6 months) by the 28-joint Disease Activity Score (DAS28). 1 of 20 (5%; (95% (confidence interval (CI) 1 to 5)) patients of the single group with <i>TLR4</i> +896AG or GG and 29 of 67 (43%; (95% CI 31 to 56)) patients with AA were in remission (p = 0.001). DAS28 of the single group with <i>TLR4</i> +896AG or GG was higher than with AA (p = 0.019). In the combination group, remission rates and DAS28 values were comparable between the genotypes. The polymorphic <i>TLR4</i> +896G allele may impair treatment response to single DMARD treatment in recent-onset rheumatoid arthritis.
In Vitro Studies of Cellular-Mediated Immunostimulation of Tumor Growth 2
Authors: Isaiah J. Fidler
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article In Vitro Studies of Cellular-Mediated Immunostimulation of Tumor Growth Get access Isaiah J. Fidler Isaiah J. Fidler Department of Pathology, School of Dental Medicine and Center for Oral Health Research, University of Pennsylvania, Philadelphia, Pennsylvania 19174 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 5, May 1973, Pages 1307–1312, https://doi.org/10.1093/jnci/50.5.1307 Published: 01 May 1973 Article history Received: 19 October 1972 Accepted: 12 January 1973 Published: 01 May 1973
Diagnostic accuracy study of anorectal manometry for diagnosis of dyssynergic defecation
Authors: Ugo Grossi, Emma V Carrington, Adil E Bharucha, Emma J Horrocks, S Mark Scott, Charles H Knowles
Journal: Gut (2015)

<h3>Objective</h3> The diagnostic accuracy of anorectal manometry (AM), which is necessary to diagnose functional defecatory disorders (FDD), is unknown. Using blinded analysis and standardised reporting of diagnostic accuracy, we evaluated whether AM could discriminate between asymptomatic controls and patients with functional constipation (FC). <h3>Design</h3> Derived line plots of anorectal pressure profiles during simulated defecation were independently analysed in random order by three expert observers blinded to health status in 85 women with FC and 85 age-matched asymptomatic healthy volunteers (HV). Using accepted criteria, these pressure profiles were characterised as normal (ie, increased rectal pressure coordinated with anal relaxation) or types I–IV dyssynergia. Interobserver agreement and diagnostic accuracy were determined. <h3>Results</h3> Blinded consensus-based assessment disclosed a normal pattern in 16/170 (9%) of all participants and only 11/85 (13%) HV. The combined frequency of dyssynergic patterns (I–IV) was very similar in FC (80/85 (94%)) and HV (74/85 (87%)). Type I dyssynergia ('paradoxical' contraction) was <i>less</i> prevalent in FC (17/85 (20%) than in HV (31/85 (36.5%), p=0.03). After statistical correction, only type IV dyssynergia was moderately useful for discriminating between FC (39/85 (46%)) and HV (17/85 (20%)) (p=0.001, positive predictive value=70.0%, positive likelihood ratio=2.3). Interobserver agreement was substantial or moderate for identifying a normal pattern, dyssynergia types I and IV, and FDD, and fair for types II and III. <h3>Conclusions</h3> While the interpretation of AM patterns is reproducible, nearly 90% of HV have a pattern that is currently regarded as 'abnormal' by AM. Hence, AM is of limited utility for distinguishing between FC and HV.
ANOMALIES AND DANGERS IN THE METRAZOL THERAPY OF SCHIZOPHRENIA
Authors: LAWRENCE E. GEESLIN, HERVEY CLECKLEY
Journal: American Journal of Psychiatry (1939)

1. Various motor phenomena bearing little resemblance to the typical grand mal epileptic seizure or to the usual description of the seizure induced by metrazol occasionally occur. 2. The possible dangers from protracted tonic reactions secondary to the usual seizures should be kept in mind. The threat of persistent anoxia may under such circumstances become ominous. 3. When metrazol therapy is being used every available means should be at hand to combat such developments. 4. All anomalous reactions which suggest yet unrecognized complications of metrazol should be reported in detail. Warnings concerning the possibility of such dangers have already been sounded.48 The practice of repeating the metrazol injection within a few minutes, though apparently safe in most cases, is not recommended.
Reply to T. Grenader et al
Authors: Sao Jiralerspong, Ana M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2009)

As discussed in our original article, metformin has pleiotropic cellular and physiologic effects, one or more of which presumably mediate its antitumor activity. We agree with Grenader et al that an anti-inflammatory action of metformin is a potential candidate for this list. However, the current clinical data for such an effect in patients with diabetes or impaired glucose tolerance (IGT) is conflicting. The largest study, derived from the Diabetes Prevention Program trial, involved patients with IGT and showed a statistically significant decrease in serum C-reactive protein (CRP) in the metformin-treated group versus the control group. This is supported by other smaller studies showing a decrease in CRP levels with metformin treatment. In contrast, an interim analysis of the Hyperinsulinemia: The Outcome of its Metabolic Effects (HOME) trial, which compared insulin with or without metformin in patients with type 2 diabetes, showed no significant change in CRP. Several other small studies provided similar results. Although the different study populations, treatment regimens, and trial designs make comparisons challenging, it is evident that a consistent clinical anti-inflammatory action of metformin, on the basis of biomarker assessment, has yet to be established in patients with diabetes or IGT. As an added complication, insulin itself appears to have contextdependent effects that may be either antior proinflammatory. As metformin acts physiologically to lower insulin levels, the final outcome on inflammation within a tumor is difficult to predict. Therefore, the effect of metformin on tumor-associated inflammation is an area that requires further study. Finally, in addition to diabetes, we note that obesity has also been linked to inflammation. Thus, if confirmed as an anti-inflammatory agent, metformin may also be useful in the treatment of tumor-associated inflammation in this related and overlapping patient subset.
A Modified Enzymatic Technique for Production of Cell Suspensions of a Murine Fibrosarcoma&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;, &lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: J J Penning, J H LeVan
Journal: JNCI Journal of the National Cancer Institute (1981)

Collagenase, elastase, and mild mechanical procedures were used to obtain numerous viable single cells in suspension from a murine fibrosarcoma of C57BL/6 origin. This technique produced suspensions with minimal debris. The suspensions were more than 90% viable and yielded over 1.25 x 10(8) cells/g of solid tumor.
TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events
Authors: Karen A. Cavassani, Makoto Ishii, Haitao Wen, Matthew A. Schaller, Pamela M. Lincoln, Nicholas W. Lukacs, Cory M. Hogaboam, Steven L. Kunkel
Journal: The Journal of Experimental Medicine (2008)

Ligands from dying cells are a source of Toll-like receptor (TLR) activating agents. Although TLR3 is known to respond to RNA from necrotic cells, the relative importance of this response in vivo during acute inflammatory processes has not been fully explored. We observed the involvement of TLR3 activation during experimental polymicrobial septic peritonitis and ischemic gut injury in the absence of an exogenous viral stimulus. In TLR3-deficient mice, increased chemokine/cytokine levels and neutrophil recruitment characterized the initial inflammatory responses in both injury models. However, the levels of inflammatory chemokines and tumor necrosis factor α quickly returned to baseline in tlr3−/− mice, and these mice were protected from the lethal effects of sustained inflammation. Macrophages from tlr3−/− mice responded normally to other TLR ligands but did not respond to RNA from necrotic neutrophils. Importantly, an immunoneutralizing antibody directed against TLR3 attenuated the generation of inflammatory chemokines evoked by byproducts from necrotic neutrophils cultured with wild-type macrophages. In vivo, anti-TLR3 antibody attenuated the tissue injury associated with gut ischemia and significantly decreased sepsis-induced mortality. Collectively, these data show that TLR3 is a regulator of the amplification of immune response and serves an endogenous sensor of necrosis, independent of viral activation.
Magnesium reduces myocardial infarct size via enhancement of adenosine mechanism in rabbits
Authors: T. Matsusaka, N. Hasebe, Y.-T. Jin, J. Kawabe, K. Kikuchi
Journal: Cardiovascular Research (2002)

Objectives: Clinical impact of magnesium (Mg) therapy remains controversial in acute myocardial infarction. We investigated the infarct size limiting effects of Mg and its mechanism in rabbits. Methods: Anesthetized rabbits underwent 30 min coronary occlusion and 3 h reperfusion in ten groups: (1) Control, (2) Low Mg, (3) Mg, (4) High Mg, (5) calcium (Ca), (6) Mg+Ca, (7) 8-phenyltheophylline (8PT), an adenosine receptor blockade, (8) 8PT+Mg, (9) α, β-methylene-adenosine diphosphate (AOPCP), a selective inhibitor of ecto-5′-nucleotidase, and (10) AOPCP+Mg groups. Infract size (IS) to area at risk (AR) was measured by triphenyltetrazorium chloride method. Results: The IS/AR ratio was significantly smaller in Mg, 27±3% (P<0.05) and High Mg, 24±2% (P<0.05) compared to Control, 50±3% and Low Mg, 42±4%. The IS limiting effects of Mg were abolished in 8PT+Mg, AOPCP+Mg and Mg+Ca. The IS/AR ratio correlated with neither rate-pressure products nor incidence of arrhythmia. Conclusion: Magnesium administration has an infarct size limiting effect independent of its effects on myocardial oxygen consumption and incidence of arrhythmia in rabbits. The infarct size limiting effect of magnesium is attributable, at least in part, to augmentation of adenosine mechanism.
A novel glyco-conjugate vaccine against fungal pathogens
Authors: Antonella Torosantucci, Carla Bromuro, Paola Chiani, Flavia De Bernardis, Francesco Berti, Chiara Galli, Francesco Norelli, Cinzia Bellucci, Luciano Polonelli, Paolo Costantino, Rino Rappuoli, Antonio Cassone
Journal: The Journal of Experimental Medicine (2005)

To generate a vaccine to protect against a variety of human pathogenic fungi, we conjugated laminarin (Lam), a well-characterized but poorly immunogenic β-glucan preparation from the brown alga Laminaria digitata, with the diphtheria toxoid CRM197, a carrier protein used in some glyco-conjugate bacterial vaccines. This Lam-CRM conjugate proved to be immunogenic and protective as immunoprophylactic vaccine against both systemic and mucosal (vaginal) infections by Candida albicans. Protection probably was mediated by anti-β-glucan antibodies as demonstrated by passive transfer of protection to naive mice by the whole immune serum, the immune vaginal fluid, and the affinity-purified anti-β-glucan IgG fractions, as well as by administration of a β-glucan–directed IgG2b mAb. Passive protection was prevented by adsorption of antibodies on Candida cells or β-glucan particles before transfer. Anti-β-glucan antibodies bound to C. albicans hyphae and inhibited their growth in vitro in the absence of immune-effector cells. Remarkably, Lam-CRM–vaccinated mice also were protected from a lethal challenge with conidia of Aspergillus fumigatus, and their serum also bound to and markedly inhibited the growth of A. fumigatus hyphae. Thus, this novel conjugate vaccine can efficiently immunize and protect against two major fungal pathogens by mechanisms that may include direct antifungal properties of anti-β-glucan antibodies.
Evaluation of Bias in Familial Risk Estimates: A Study of Common Cancers Using Swedish Population-based Registers
Authors: Monica Leu, Marie Reilly, Kamila Czene
Journal: JNCI Journal of the National Cancer Institute (2008)

Bias in estimates of familial cancer may result if population-based registers fail to identify relatives as affected when disease occurs before the start-up of registration (ie, "left-truncation" of family history).Apparent familial relative risks (among offspring of parents with cancer) of colorectal, lung, breast, and prostate cancers and melanoma in a Swedish cohort were compared with relative risks in a simulated population. The study cohort (approximately 7 million individuals) was based on the Swedish MultiGenerational Register linked to the Swedish Cancer Register for the period 1961-2002. A similar population of related individuals (approximately 7 million) with complete family information was simulated by using the R-package PopLab and used to estimate the sensitivity of the observed family history. This sensitivity was then used to calculate corrected age group-specific and overall risks, which were compared with the apparent familial risks of cancer in the cohort.The apparent familial risks for colorectal, lung, breast, and prostate cancers and melanoma were 1.99 (95% confidence interval [CI] = 1.85 to 2.14), 2.05 (95% CI = 1.86 to 2.26), 1.84 (95% CI = 1.76 to 1.92), 2.33 (95% CI = 2.19 to 2.48), and 2.68 (95% CI = 2.35 to 3.07), with corresponding absolute rates of 3.69, 2.59, 16.05, 10.38, and 2.96 per 10 000 person-years, among offspring of parents diagnosed with the same cancer. Corrected age group-specific and overall estimates of the familial risks were close to these apparent risks for all studied cancers (all approximately 2.0), except for melanoma. For melanoma, the corrected estimate of 3.18 (95% CI = 2.73 to 3.64) was somewhat larger than the apparent estimate and was not included in the confidence interval for the apparent estimate. When the exposure of interest was a parent affected at a younger age, this bias was more pronounced; the apparent estimate for melanoma changed from 4.07 (95% CI = 3.21 to 5.16) to 5.67 (95% CI = 4.51 to 6.83) after correction.For common cancers, risk estimates from the Swedish MultiGenerational cohort do not generally appear to be biased by left-truncation.
Salivary pepsin to diagnose GORD?
Authors: Nimish Vakil
Journal: Gut (2014)

GORD has been defined by international consensus based on symptoms of heartburn and regurgitation.1 While this definition is useful for patients with the typical reflux syndrome, these symptoms may not be present in patients with extra-oesophageal GORD. The limitations of pH testing and endoscopy were highlighted in a recent study that demonstrated that each failed to identify approximately 30% of patients with proven GORD.2 A test that establishes a diagnosis of GORD at low cost with minimal intervention would have great utility. The presence of pepsin in saliva or sputum has been proposed as a surrogate marker for reflux disease, albeit one that tells us nothing about a causal relationship between reflux and symptoms.

Pepsin may be detected in sputum or saliva by enzymatic or immunological tests.3 Enzymatic tests have several limitations and are difficult to obtain and standardise in practice settings. Attention has therefore focused on immunologic assays with polyclonal and monoclonal antibodies that have been patented and commercialised.3

The question for the clinician is whether salivary pepsin determination is a diagnostic tool that is helpful in clinical practice. For a diagnostic test to be useful in clinical practice, we should be able to demonstrate that the test not only improves our accuracy but that it results in a treatment decision that changes patient outcomes.4 Tests that improve accuracy modestly but don't change management or outcomes have little …
Gamma/delta T lymphocytes in the blood of patients with sarcoidosis.
Authors: M L Wilsher, M Hallowes, N M Birchall
Journal: Thorax (1995)

BACKGROUND--Gamma/delta T lymphocytes are thought to have a role in granulomatous immune responses at peripheral sites of antigen contact such as the gut, skin and lung. The aim of this study was to determine if gamma/delta T lymphocytes are increased in the peripheral blood of patients with active sarcoidosis. METHODS--Peripheral blood from 21 untreated patients with a new presentation of sarcoidosis (12M, 9F), 20 normal volunteers (12M, 8F), and 12 patients with cavitary pulmonary tuberculosis were subjected to Ficoll Hypaque separation and flow cytometry analysis using monoclonal antibodies to CD3, 4, 8, 25, HLA-DR and gamma/delta T cell receptor. RESULTS--All patients with sarcoidosis had compatible chest radiographs and all were Mantoux negative in spite of previous BCG vaccination. In all but one patient histological examination showed non-caseating granuloma. There was no difference in the mean percentage or absolute numbers of gamma/delta positive peripheral blood lymphocytes between the three populations. Thirteen patients with sarcoidosis had an absolute lymphopenia and the mean percentage of CD3 positive peripheral blood lymphocytes in the group with sarcoidosis was lower than the other two groups. The percentage of CD25 and HLA-DR positive cells was higher in the group with sarcoidosis, supporting the fact that these patients had active disease. CONCLUSION--Gamma/delta T lymphocytes are not increased in the peripheral blood of patients with sarcoidosis and are unlikely to have a role in the pathogenesis of this disease.
The CD49d/CD29 complex is physically and functionally associated with CD38 in B-cell chronic lymphocytic leukemia cells
Authors: A Zucchetto, T Vaisitti, D Benedetti, E Tissino, V Bertagnolo, D Rossi, R Bomben, M Dal Bo, M I Del Principe, A Gorgone, G Pozzato, G Gaidano, G Del Poeta, F Malavasi, S Deaglio, V Gattei
Journal: Leukemia (2012)
Online Myocardial Viability Assessment in the Catheterization Laboratory via NOGA Electroanatomic Mapping
Authors: Mariann Gyöngyösi, Heinz Sochor, Aliashgar Khorsand, Lior Gepstein, Dietmar Glogar
Journal: Circulation (2001)

The aim of this prospective study was to investigate the concordance between quantitative resting (201)Tl uptake as an established myocardial viability index and the electrical activity of the heart, determined by NOGA nonfluoroscopic electroanatomic mapping.The myocardial resting and late resting thallium uptakes of 384 myocardial segments from 32 patients (27 males aged 65+/-8 years) with previous myocardial infarction and chronic stable angina were compared with unipolar voltage potentials and local shortening of the left ventricle as assessed by electroanatomic mapping. The quantitative thallium uptake data were analyzed by polar map analysis by division into 12 comparable myocardial segments, as represented in electroanatomic mapping images. Unipolar voltage potentials exhibited a significant logarithmic correlation with both resting and late resting thallium uptake (attenuation corrected: r=0.660 and r=0.744; non-attenuation corrected: r=0.623 and r=0.721). Receiver operator characteristic analyses revealed unipolar voltage cutoff points of 12.0 mV (predictive accuracy 0.853, P< 0.001; sensitivity/specificity 81%) for normal myocardium and 6.4 mV (predictive accuracy 0.901, P< 0.001; sensitivity/specificity 82%) for nonviable myocardium assessed by attenuation-corrected (201)Tl late resting images and of 12.7 mV (predictive accuracy 0.822, P<0.001; sensitivity/specificity 75%) and 6.5 mV (predictive accuracy 0.808, P<0.001; sensitivity/specificity 73%) for non-attenuation-corrected late resting (201)Tl images.These results indicate that the unipolar voltage potentials obtained by electroanatomic mapping correlate well with standard quantitative late resting (201)Tl imaging for the evaluation of myocardial viability; thus, NOGA endocardial mapping provides useful "online" data at the time of catheterization, especially when information from other methods for viability assessment is unavailable.