tbuckley/cabot-search huggingface dataset:
Patients with systemic lupus erythematosus and Jaccoud's arthropathy: a clinical subset with an increased C reactive protein response?
Authors: P E Spronk, E J ter Borg, C G Kallenberg
Journal: Annals of the Rheumatic Diseases (1992)

Jaccoud's arthropathy is a chronic deforming synovitis occurring in a subset of patients with systemic lupus erythematosus (SLE). To evaluate whether patients with SLE and Jaccoud's arthropathy behave differently in their acute phase reaction from patients with SLE without Jaccoud's arthropathy, a prospective study was carried out on 72 consecutive patients with SLE. Patients were assessed for Jaccoud's arthropathy according to a protocol, disease activity was scored, and laboratory tests, including tests for C reactive protein, were performed. Seven patients were classified as having definite Jaccoud's arthropathy. In those patients the serum concentrations of C reactive protein were higher than in those without Jaccoud's arthropathy, whereas disease activity scores and treatment were comparable. Additionally, patients with Jaccoud's arthropathy had a longer disease duration and a longer history of arthritis than those without, whereas IgM rheumatoid factor was observed more often. The increased concentration of C reactive protein in patients with Jaccoud's arthropathy is compatible with a persistent inflammatory reaction. Serial testing of C reactive protein in combination with other laboratory parameters may be a guideline for treatment in patients with SLE and Jaccoud's arthropathy.
Fluorescence endoscopic detection of murine colitis-associated colon cancer by topically applied enzymatically rapid-activatable probe
Authors: Makoto Mitsunaga, Nobuyuki Kosaka, Peter L Choyke, Matthew R Young, Christopher R Dextras, Shakir M Saud, Nancy H Colburn, Masayo Sakabe, Tetsuo Nagano, Daisuke Asanuma, Yasuteru Urano, Hisataka Kobayashi
Journal: Gut (2012)

Screening colonoscopy to monitor for early colitis-associated colon cancer (CAC) is difficult due to the aberrant mucosal patterns associated with long-standing colitis. The aim of this study was to develop a rapid fluorescent detection method for use during colonoscopy for improving the detection of CAC utilising a topically applied enzymatically activatable probe (gGlu-HMRG) which fluoresces in the presence of γ-glutamyltranspeptidase (GGT), an enzyme associated with cancer.Expression of GGT in colon cell lines was examined with fluorescence microscopy and flow cytometry. A mouse model (azoxymethane/dextran sulphate sodium) of CAC was used and mice were examined with white light and fluorescence colonoscopy before and after topical gGlu-HMRG administration.Expression of GGT, although variable, was higher in human colon cancer cells than normal human colon cells. Using fluorescence colonoscopy in mice, gGlu-HMRG fluorescent lesions were detected 5 min after topical administration and fluorescence persisted for at least 30 min. Fluorescence guided biopsy revealed all fluorescent lesions that contained cancer or dysplasia (n=16), whereas three out of 12 non-fluorescent lesions contained low grade dysplasia and others did not contain neoplastic histology. Microscopic inflammatory infiltration also had variable fluorescence but in general was much lower (∼10-fold) in signal than cancer. Repeat fluorescence endoscopy allowed individual tumours to be monitored.These results suggest that gGlu-HMRG can improve endoscopic detection of CAC with a higher target to background ratio than conventional white light colonoscopy. This could be of benefit to patients with long-standing colitis who must undergo repeated screening colonoscopies.
Effect of patiromer on reducing serum potassium and preventing recurrent hyperkalaemia in patients with heart failure and chronic kidney disease on <scp>RAAS</scp> inhibitors
Authors: Bertram Pitt, George L. Bakris, David A. Bushinsky, Dahlia Garza, Martha R. Mayo, Yuri Stasiv, Heidi Christ‐Schmidt, Lance Berman, Matthew R. Weir
Journal: European Journal of Heart Failure (2015)

Aims We evaluated the effects of patiromer, a potassium (K + )‐binding polymer, in a pre‐specified analysis of hyperkalaemic patients with heart failure ( HF ) in the OPAL‐HK trial. Methods and results Chronic kidney disease ( CKD ) patients on renin–angiotensin–aldosterone system inhibitors ( RAASi ) with serum K + levels ≥5.1 mEq /L to &lt;6.5 mEq /L ( n = 243) received patiromer (4.2 g or 8.4 g BID initially) for 4 weeks (initial treatment phase); the primary efficacy endpoint was mean change in serum K + from baseline to week 4. Eligible patients (those with baseline K + ≥5.5 mEq /L to &lt;6.5 mEq /L and levels ≥3.8 mEq /L to &lt;5.1 mEq /L at the end of week 4) entered an 8‐week randomized withdrawal phase and were randomly assigned to continue patiromer or switch to placebo; the primary efficacy endpoint was the between‐group difference in median change in the serum K + over the first 4 weeks of that phase. One hundred and two patients (42%) had heart failure ( HF ). The mean [± standard error ( SE )] change in serum K + from baseline to week 4 was −1.06 ± 0.05 mEq /L [95% confidence interval ( CI ), −1.16,−0.95; P &lt; 0.001]; 76% (95% CI , 69,84) achieved serum K + , 3.8 mEq /L to &lt;5.1 mEq /L. In the randomized withdrawal phase, the median increase in serum K + from baseline of that phase was greater with placebo ( n = 22) than patiromer ( n = 27) ( P &lt; 0.001); recurrent hyperkalaemia (serum K + , ≥5.5 mEq /L) occurred in 52% on placebo and 8% on patiromer ( P &lt; 0.001). Mild‐to‐moderate constipation was the most common adverse event (11%); hypokalaemia occurred in 3%. Conclusion In patients with CKD and HF who were hyperkalaemic on RAASi , patiromer was well tolerated, decreased serum K + , and, compared with placebo, reduced recurrent hyperkalaemia.
Factors affecting mortality and morbidity after surgery for obstructive jaundice.
Authors: J M Dixon, C P Armstrong, S W Duffy, R A Elton, G C Davies
Journal: Gut (1984)

<h3>Background</h3> A current concern is the number of people dying in hospital who have no medical need, or wish, to be there (Marie Curie Cancer Care, 2012). 72% of people would prefer to die at home (ComRes, 2014), yet just 25% do so, with 50% dying in hospital (Gomes, Calanzani, Higginson, 2011). Instinctively, hospice-led initiatives play an important role in minimising inappropriate hospital usage at the end of life, but there is a lack of robust data. <h3>Aim</h3> To establish the impact of different hospice led innovations on a) reducing the number of hospital bed days during the last 90 days of life, b) place of death and other secondary outcome measures: the number of emergency and inpatient admissions and discharges to a hospice in the last 90 days of life. <h3>Method</h3> Mixed methods study with a quantitative quasi-experimental longitudinal design employing a ‘difference of difference’ analysis of HES data to assess the impact on hospital utilisation in the last 90 days of life. Any encountered differences are compared to control cohorts. Stakeholders were qualitatively interviewed through open-ended, semi-structured and structured interviews followed by narrative, framework and content analysis respectively. <h3>Results</h3> Quantitative: ongoing, however, we anticipate data showing a reduction in the number of hospital beds days, in the last 90 days of life, within the locality of the intervention hospice. Qualitative: interviewed 188 people, including 24 patients and carers, across 27 interventions at 25 sites providing 31 recurrent topics of which the five most relatively frequent were the process of development, collaboration, the intervention group, staff roles and professional culture. <h3>Conclusions</h3> Qualitative evaluation of these innovations shows benefit to the patient experience and factors critical to success and replicability. Quantitative data will show the impact on NHS resources, and together the findings will enable better evidence-based commissioning, supporting service redesign at a local level. Final report due Sept. 2018.
Dietary Patterns During Adolescence and Risk of Type 2 Diabetes in Middle-Aged Women
Authors: Vasanti S. Malik, Teresa T. Fung, Rob M. van Dam, Eric B. Rimm, Bernard Rosner, Frank B. Hu
Journal: Diabetes Care (2011)

OBJECTIVE Whether dietary habits early in life can affect risk of type 2 diabetes (T2DM) in adulthood is unknown. We evaluated the relationship between dietary patterns during adolescence and risk of T2DM in midlife. RESEARCH DESIGN AND METHODS We examined the 7-year incidence of T2DM in relation to dietary patterns during high school among 37,038 participants in the Nurses’ Health Study II cohort, who completed a food-frequency questionnaire about their diet during high school. Dietary patterns were derived by factor analysis. Cox proportional hazards regression was used to estimate relative risk (RR) and 95% CI. RESULTS The prudent pattern, characterized by healthy foods, was not associated with risk of T2DM. The Western pattern, characterized by desserts, processed meats, and refined grains, was associated with 29% greater risk of T2DM (RR 1.29; 95% CI 1.00–1.66; P trend 0.04), after adjusting for high school and adult risk factors comparing extreme quintiles, but was attenuated after adjusting for adult weight change (1.19; 0.92–1.54). Women who had high Western pattern scores in high school and adulthood had an elevated risk of T2DM compared with women who had consistent low scores (1.82; 1.35–2.45), and this association was partly mediated by adult BMI (1.15; 0.85–1.56). CONCLUSIONS A Western dietary pattern during adolescence may increase risk of T2DM in later life, partly through adult weight gain. Preventive measures should be aimed at developing healthy dietary habits that begin in early life and continue through adulthood.
Rapidly progressive adenomatous polyposis in a patient with germline mutations in both the APC and MLH1 genes: the worst of two worlds
Authors: R Scheenstra
Journal: Gut (2003)

The two most common inherited forms of colorectal cancer are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Simultaneous inheritance of both an <i>APC</i> gene mutation and a mismatch repair gene (for example, <i>MLH1</i>) mutation has never been described. In the present case report, we report rapidly progressive adenomatous polyposis in a 10 year old boy with a germline frame shift mutation in the <i>APC</i> gene and a germline splice site mutation in the <i>MLH1</i> gene. Immunohistochemical investigations showed abnormal expression of β-catenin in early adenomas with low grade dysplasia, attributed to the <i>APC</i> gene mutation. Subsequent loss of function of the <i>MLH1</i> gene, as shown by absent immunostaining of its protein in adenomas with high grade dysplasia, may well have caused the rapid progression to high grade dysplasia in many of the adenomas.
Phase II, Randomized, Controlled, Double-Blinded Trial of Weekly Elesclomol Plus Paclitaxel Versus Paclitaxel Alone for Stage IV Metastatic Melanoma
Authors: Steven O'Day, Rene Gonzalez, David Lawson, Robert Weber, Laura Hutchins, Clay Anderson, Jonathan Haddad, Steven Kong, Anthony Williams, Eric Jacobson
Journal: Journal of Clinical Oncology (2009)

Purpose Elesclomol is a novel, small-molecule, oxidative stress inducer believed to exert selective cytotoxicity by increasing intracellular concentrations of reactive oxygen species, which results in cell death via mitochondrial apoptosis. We evaluated whether the addition of elesclomol to weekly paclitaxel could improve efficacy in patients with stage IV metastatic melanoma. Patients and Methods We randomly assigned patients with metastatic melanoma, measurable disease, and one or fewer prior chemotherapy regimens to elesclomol 213 mg/m 2 plus paclitaxel 80 mg/m 2 (E + P) or to paclitaxel 80 mg/m 2 alone at a 2:1 ratio; regimens were given as a 1-hour intravenous infusion weekly, during 3 of every 4 weeks until disease progression per Response Evaluation Criteria in Solid Tumors or death occurred. Patients who experienced progression were unblended, and patients on paclitaxel alone were permitted to cross over to E + P. The primary efficacy end point was progression-free survival (PFS); secondary end points were response rate (RR), toxicity, and overall survival (OS; analyzed post hoc). Results At 21 US sites, 53 patients were randomly assigned to E + P, and 28 patients were randomly assigned to paclitaxel. The addition of elesclomol to paclitaxel yielded a doubling of median PFS (112 v 56 days) and a 41.7% risk reduction for disease progression/death (hazard ratio, 0.583; P = .035). Respective RRs for the E + P and paclitaxel groups were 15% and 3%; median OS was 11.9 v 7.8 months. Of patients on paclitaxel alone, 19 (68%) of 28 crossed over to E + P after they experienced progression. Weekly E + P was well tolerated. Conclusion E + P resulted in a statistically significant doubling of median PFS, with an acceptable toxicity profile and encouraging OS. A multinational, phase III trial (SYMMETRY) of E + P compared with paclitaxel alone in metastatic melanoma has closed.
Hedgehog Signaling Alters Reliance on EGF Receptor Signaling and Mediates Anti-EGFR Therapeutic Resistance in Head and Neck Cancer
Authors: Stephen B. Keysar, Phuong N. Le, Ryan T. Anderson, J. Jason Morton, Daniel W. Bowles, Jeramiah J. Paylor, Brian W. Vogler, Jackie Thorburn, Pamela Fernandez, Magdalena J. Glogowska, Sarah M. Takimoto, Daniel B. Sehrt, Gregory N. Gan, Justin R. Eagles-Soukup, Hilary Serracino, Fred R. Hirsch, M. Scott Lucia, Andrew Thorburn, John I. Song, Xiao-Jing Wang, Antonio Jimeno
Journal: Cancer Research (2013)

Abstract The EGF receptor (EGFR)-directed monoclonal antibody cetuximab is the only targeted therapy approved for the treatment of squamous cell carcinoma of the head and neck (HNSCC) but is only effective in a minority of patients. Epithelial-to-mesenchymal transition (EMT) has been implicated as a drug resistance mechanism in multiple cancers, and the EGFR and Hedgehog pathways (HhP) are relevant to this process, but the interplay between the two pathways has not been defined in HNSCC. Here, we show that HNSCC cells that were naturally sensitive to EGFR inhibition over time developed increased expression of the HhP transcription factor GLI1 as they became resistant after long-term EGFR inhibitor exposure. This robustly correlated with an increase in vimentin expression. Conversely, the HhP negatively regulated an EGFR-dependent, EMT-like state in HNSCC cells, and pharmacologic or genetic inhibition of HhP signaling pushed cells further into an EGFR-dependent phenotype, increasing expression of ZEB1 and VIM. In vivo treatment with cetuximab resulted in tumor shrinkage in four of six HNSCC patient-derived xenografts; however, they eventually regrew. Cetuximab in combination with the HhP inhibitor IPI-926 eliminated tumors in two cases and significantly delayed regrowth in the other two cases. Expression of EMT genes TWIST and ZEB2 was increased in sensitive xenografts, suggesting a possible resistant mesenchymal population. In summary, we report that EGFR-dependent HNSCC cells can undergo both EGFR-dependent and -independent EMT and HhP signaling is a regulator in both processes. Cetuximab plus IPI-926 forces tumor cells into an EGFR-dependent state, delaying or completely blocking tumor recurrence. Cancer Res; 73(11); 3381–92. ©2013 AACR.
Mechanism of ionomycin-induced intracellular alkalinization of rat hepatocytes
Authors: M. Sawkat Anwer
Journal: Hepatology (1993)

Calcium ionophores such as ionomycin and A23187 are often used to determine the role of intracellular Ca++ in cellular processes. Ionomycin but not Ca+(+)-mobilizing agonists increases basal intracellular pH in hepatocytes. To explain this difference in effects of agents that increase intracellular Ca++ concentration, the mechanism of ionomycin-induced increases in basal intracellular pH in isolated rat hepatocytes was studied. Changes in intracellular pH and intracellular Ca++ concentration were measured with the fluorescent probes BCECF (2',7'-bis-2-[carboxyethyl ester]-5[6]carboxyfluorescein) and quin-2, respectively. Ionomycin produced dose-dependent increases in intracellular pH and intracellular Ca++ concentration, with the increase in intracellular Ca++ concentration preceded by the increase in intracellular pH. Ionomycin-induced increases in intracellular pH were not affected by 1 mmol/L amiloride, 100 mumol/L diisothiocyanostilbene disulfonate or removal of extracellular Na+, indicating that the effect is not mediated by Na+/H+ exchange, Cl-/HCO3- exchange or Na+/HCO3- cotransport. Ionomycin failed to increase intracellular pH or intracellular Ca++ concentration in the absence of extracellular Ca++, and both intracellular pH and intracellular Ca++ concentration increased promptly when extracellular Ca++ was reintroduced. Ionomycin-induced increases in intracellular Ca++ concentration but not intracellular pH were smaller in hepatocytes loaded with the Ca++ buffering agent MAPTA. Thapsigargin increased intracellular Ca++ concentration but failed to increase intracellular pH. Thus the effect of ionomycin is independent of the effect of ionomycin on intracellular Ca++ concentration and dependent on extracellular intracellular Ca++ concentration. Experimental conditions that produce cell depolarization did not increase basal intracellular pH but lowered ionomycin-induced increases in intracellular pH by 25% without affecting increases in intracellular Ca++ concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
The Clinical Utility of the Perinatal Autopsy
Authors: D N Saller, K B Lesser, U Harrel, B B Rogers, C E Oyer
Journal: JAMA (1995)

<h3>Objective.</h3> —To evaluate the clinical utility of the perinatal autopsy in determining the cause of a perinatal death. <h3>Design.</h3> —Retrospective observational survey. <h3>Setting.</h3> —University-affiliated, private, tertiary care hospital, limited to obstetrics, gynecology, and neonatology. <h3>Subjects.</h3> —All fetal deaths and neonatal deaths from 1990 and 1991 at Women and Infants Hospital, Providence, RI, were reviewed. Fetal deaths with a gestational age of less than 20 weeks and neonatal deaths occurring more than 48 hours after birth were excluded. <h3>Main Outcome Measures.</h3> —A clinical medical record review assessed the clinical diagnosis. Pathology records were reviewed independently. The clinical and autopsy diagnoses were compared and categorized as follows: (1) confirm (clinical and autopsy diagnoses concordant); (2) change (clinical and autopsy diagnoses discordant); (3) add (significant unexpected findings noted on the autopsy although the clinical diagnosis was not altered); (4) autopsy inconclusive; (5) autopsy not done or not available. <h3>Results.</h3> —Of 168 perinatal deaths, an autopsy was not obtained in 26.2% and was inconclusive in 24.2% of cases with an autopsy. Of 94 patients with conclusive autopsies, in 55.3%, the pathologic diagnosis confirmed the clinical diagnosis, and in 44.7%, it changed or significantly added to the clinical diagnosis. <h3>Conclusions.</h3> —These findings support the clinical relevance of the perinatal autopsy. As few published reports directly address the specific yield of the autopsy among fetal and neonatal deaths, these results may be useful in counseling patients who are considering a perinatal autopsy. (<i>JAMA</i>. 1995;273:663-665)
IMMUNITY IN MUMPS
Authors: Lewis W. Kane, John F. Enders
Journal: The Journal of Experimental Medicine (1945)

1. Fifty-one patients exhibiting signs and symptoms compatible with the clinical syndrome of acute aseptic meningoencephalitis have been studied by means of the complement fixation test for the demonstration of antibody reacting with the virus of mumps or its products. 2. In 17 of these individuals in whom the clinical diagnosis could be made with assurance because of an associated enlargement of the salivary glands, the test yielded evidence of recent infection with the virus. 3. In 16 patients without involvement of the salivary glands the results of the test likewise indicated recent infection with this virus. 4. In the remaining 18 patients the test gave no evidence of a recent infection with the virus. 5. Except for histories of recent exposure obtained from certain of the individuals in whom the complement fixation test was considered to be positive, the characteristics of the disease and the data afforded by the usual laboratory studies failed to distinguish the last 2 groups. 6. On the basis of these findings, it is concluded that the complement fixation test should be of value in the diagnosis of those cases of acute aseptic meningoencephalitis in which the virus of mumps is the etiologic agent and in which involvement of the salivary glands is slight or absent.
E-cadherin gene polymorphisms in asthma patients using inhaled corticosteroids
Authors: D. Ierodiakonou, D.S. Postma, G.H. Koppelman, H.M. Boezen, J. Gerritsen, N. ten Hacken, W. Timens, J.M. Vonk
Journal: European Respiratory Journal (2011)

E-cadherins form intercellular junctions that maintain epithelial integrity. Epithelial integrity is impaired in asthma and can be restored by inhaled corticosteroids (ICSs). Our aim was to investigate the association of CDH1 gene polymorphisms (single-nucleotide polymorphisms (SNPs)) with airway remodelling, inflammation and forced expiratory volume in 1 s (FEV 1 ) decline in asthma patients and assess whether ICSs modulate these effects. Bronchial biopsies of 138 asthmatics were available (population 1). Associations of 17 haplotype-tagging SNPs with epithelial E-cadherin expression, biopsy parameters and FEV 1 /vital capacity (VC) ratio were tested. FEV 1 and VC data were collected in 281 asthmatics with 30-yr follow-up (population 2). Linear mixed-effect models were used to assess associations of SNPs with FEV 1 decline. Seven out of the 17 SNPs were associated with airway remodelling, three with CD8+ T-cell counts, two with eosinophil counts and seven with FEV 1 decline. All associations occurred only in patients using ICS. In general, alleles associated with less remodelling correlated with less FEV 1 decline and higher FEV 1 /VC. Decreased epithelial E-cadherin expression was associated with five SNPs in non-ICS users. In conclusion, our data show that CDH1 polymorphisms are associated with epithelial E-cadherin expression and suggest that epithelial adhesion is an important contributor to airway remodelling and lung function in asthma. These effects are modified by the use of inhaled corticosteroids.
New insights to the MLL recombinome of acute leukemias
Authors: C Meyer, E Kowarz, J Hofmann, A Renneville, J Zuna, J Trka, R Ben Abdelali, E Macintyre, E De Braekeleer, M De Braekeleer, E Delabesse, M P de Oliveira, H Cavé, E Clappier, J J M van Dongen, B V Balgobind, M M van den Heuvel-Eibrink, H B Beverloo, R Panzer-Grümayer, A Teigler-Schlegel, J Harbott, E Kjeldsen, S Schnittger, U Koehl, B Gruhn, O Heidenreich, L C Chan, S F Yip, M Krzywinski, C Eckert, A Möricke, M Schrappe, C N Alonso, B W Schäfer, J Krauter, D A Lee, U zur Stadt, G Te Kronnie, R Sutton, S Izraeli, L Trakhtenbrot, L Lo Nigro, G Tsaur, L Fechina, T Szczepanski, S Strehl, D Ilencikova, M Molkentin, T Burmeister, T Dingermann, T Klingebiel, R Marschalek
Journal: Leukemia (2009)
ENDOCRINE IMBALANCE AND ITS RELATION TO CHRONIC ARTHRITIS
Authors: G. L. K. Pringle
Journal: BMJ (1928)

CHRONIC ARTHRITIS.[THE DitarTw 751 down, accurately and precisely, these masked forms of tubereulosis in the eye, in the nose, in the larynx, and evsen in internial organs and systenms, at a time when diagnosis is -otherwise extremely difficult and treatment relativ ely easy.Certainly in such cases the effects of tuberculini used as a remedy by an expert are often magical in suddeniness anid completeness.Geeneral hospitals, and some special hospitals, might help earnest students and suffering hutimaniity by establish- ing a speeial ward and an out-patient department for the studv of clhronic tubetculosis in both its common and erratic formns.