tbuckley/cabot-search huggingface dataset:
Genetic commonality between inflammatory bowel disease and sarcoidosis: the beginning of the end or the end of the beginning?
Authors: S. Cerri, R.M. du Bois, P. Spagnolo
Journal: European Respiratory Journal (2011)

Crohn's disease (CD) and ulcerative colitis, collectively known as inflammatory bowel disease (IBD), and sarcoidosis are multifactorial disorders thought to result from complex interactions between environmental stimuli ( e.g. infectious agents), susceptibility genes (which may predispose to the development of granulomatous inflammation) and modifier genes (which may affect disease phenotype in people already susceptible). Neither IBD nor sarcoidosis is the result of defects in a single major gene or chemical pathway; instead, multiple genes, each contributing a relatively minor effect, are likely to be involved. In addition to the granulomatous histopathology, both diseases share a number of similarities in terms of ocular, dermatological and joint manifestations, although sarcoidosis rarely involves the gastrointestinal tract and IBD rarely involves the lung. Immunological, bacteriological and genetic data support a link between CD and sarcoidosis. Both disorders share a similar, yet distinct, immune response, histologically defined by non-caseating granulomas. Up to 50% of patients with CD have been reported to test positive for Kveim antigens, although these data are not replicated in all studies 1. Mycobacteria have been detected in intestinal tissue of patients with CD and in the lungs of patients with sarcoidosis 2, 3. A CD4/CD8 lymphocyte ratio >3.5 on bronchoalveolar lavage (BAL) is commonly observed in sarcoidosis, often preceding granuloma formation 4, with a similar expansion of T-cell subsets demonstrated in the lungs of patients with CD 5. CD4 lymphocytes are activated in the intestinal mucosa of patients with CD, suggesting a cell-mediated disease mechanism in the gut similar to that displayed in pulmonary sarcoidosis. Furthermore, both in sarcoidosis and CD the concept of a genetic component is supported by disease being more common in monozygotic twins compared with dizygotic twins. In contrast with these similarities, tuberculin anergy, salivary gland involvement, the classical lymph and salivary gland …
Reactive Oxygen Species–Activated Ca/Calmodulin Kinase IIδ Is Required for Late <i>I</i> <sub>Na</sub> Augmentation Leading to Cellular Na and Ca Overload
Authors: Stefan Wagner, Hanna M. Ruff, Sarah L. Weber, Sarah Bellmann, Thomas Sowa, Timo Schulte, Mark E. Anderson, Eleonora Grandi, Donald M. Bers, Johannes Backs, Luiz Belardinelli, Lars S. Maier
Journal: Circulation Research (2011)

Rationale: In heart failure Ca/calmodulin kinase (CaMK)II expression and reactive oxygen species (ROS) are increased. Both ROS and CaMKII can increase late I Na leading to intracellular Na accumulation and arrhythmias. It has been shown that ROS can activate CaMKII via oxidation. Objective: We tested whether CaMKIIδ is required for ROS-dependent late I Na regulation and whether ROS-induced Ca released from the sarcoplasmic reticulum (SR) is involved. Methods and Results: 40 μmol/L H 2 O 2 significantly increased CaMKII oxidation and autophosphorylation in permeabilized rabbit cardiomyocytes. Without free [Ca] i (5 mmol/L BAPTA/1 mmol/L Br 2 -BAPTA) or after SR depletion (caffeine 10 mmol/L, thapsigargin 5 μmol/L), the H 2 O 2 -dependent CaMKII oxidation and autophosphorylation was abolished. H 2 O 2 significantly increased SR Ca spark frequency (confocal microscopy) but reduced SR Ca load. In wild-type (WT) mouse myocytes, H 2 O 2 increased late I Na (whole cell patch-clamp). This increase was abolished in CaMKIIδ −/− myocytes. H 2 O 2 -induced [Na] i and [Ca] i accumulation (SBFI [sodium-binding benzofuran isophthalate] and Indo-1 epifluorescence) was significantly slowed in CaMKIIδ −/− myocytes (versus WT). CaMKIIδ −/− myocytes developed significantly less H 2 O 2 -induced arrhythmias and were more resistant to hypercontracture. Opposite results (increased late I Na , [Na] i and [Ca] i accumulation) were obtained by overexpression of CaMKIIδ in rabbit myocytes (adenoviral gene transfer) reversible with CaMKII inhibition (10 μmol/L KN93 or 0.1 μmol/L AIP [autocamtide 2–related inhibitory peptide]). Conclusions: Free [Ca] i and a functional SR are required for ROS activation of CaMKII. ROS-activated CaMKIIδ enhances late I Na , which may lead to cellular Na and Ca overload. This may be of relevance in hear failure, where enhanced ROS production meets increased CaMKII expression.
Phase I Trial of 17-Allylamino-17-Demethoxygeldanamycin in Patients With Advanced Cancer
Authors: Matthew P. Goetz, David Toft, Joel Reid, Matthew Ames, Bridget Stensgard, Stephanie Safgren, Araba A. Adjei, Jeff Sloan, Pamela Atherton, Vlad Vasile, Sandra Salazaar, Alex Adjei, Gary Croghan, Charles Erlichman
Journal: Journal of Clinical Oncology (2005)

We determined the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLT) of 17-allylamino-17-demethoxygeldanamycin (17-AAG) when infused on days 1, 8, and 15 of a 28-day cycle in advanced solid tumor patients. We also characterized the pharmacokinetics of 17-AAG, its effect on chaperone and client proteins, and whether cytochrome P450 (CYP) 3A5 and NAD(P)H:quinone oxidoreductase 1 (NQO1) polymorphisms affected 17-AAG disposition or toxicity.An accelerated titration design was used. Biomarkers were measured in peripheral-blood mononuclear cells (PBMCs) at baseline and on days 1 and 15, and pharmacokinetic analysis was performed on day 1 of cycle 1. CYP3A5*3 and NQO1*2 genotypes were determined and correlated with pharmacokinetics and toxicity.Twenty-one patients received 52 courses at 11 dose levels. DLTs at 431 mg/m(2) were grade 3 bilirubin (n = 1), AST (n = 1), anemia (n = 1), nausea (n = 1), vomiting (n = 1), and myalgias (n = 1). No tumor responses were seen. 17-AAG consistently increased heat shock protein (Hsp) 70 levels in PBMCs. At the MTD, the clearance and half-life (t(1/2)) of 17-AAG were 11.6 L/h/m(2) and 4.15 hours, respectively; whereas the active metabolite 17-aminogeldanamycin had a t(1/2) of 7.63 hours. The CYP3A5*3 and NQO1*2 polymorphisms were not associated with 17-AAG toxicity. The CYP3A5*3 polymorphism was associated with higher 17-AAG clearance.The MTD of weekly 17-AAG is 308 mg/m(2). 17-AAG induced Hsp70 in PBMCs, indicating that Hsp90 has been affected. Further evaluation of 17-AAG is ongoing using a twice-weekly regimen, and this schedule of 17-AAG is being tested in combination with chemotherapy.
Estimating the Prevalence of Low Glomerular Filtration Rate Requires Attention to the Creatinine Assay Calibration
Authors: Josef Coresh, Garabed Eknoyan, Andrew S. Levey
Journal: Journal of the American Society of Nephrology (2002)

To the Editor:

In the May issue of JASN , Clase et al . ([1][1]) report a much higher estimate of the prevalence of low glomerular filtration rate (GFR) than recently published in the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines, “
Transtracheal oxygen therapy as an effective treatment in patients suffering from severe hypoxemia and with high flow oxygen requirement: Description of two cases
Authors: Stefano Baglioni, Maurizio Dottorini, Elvio Scoscia, Emanuela Albo, Amir Eslami, Elisabetta Fiandra, Marta Abbritti, Oronzo Penza
Journal: European Respiratory Journal (2011)

Patients suffering from severe hypoxemia requiring high flow oxygen administration are very difficult to treat at home and have a poor quality of life. Transtracheal oxygen therapy (TTO) has been used for many years as an alternative to conventional device for oxygen treatment, but it is only used in a small portion of patients requiring long term O2 therapy (LTOT) and nowadays this tecnique is rarely used, al least in our country.

We describe the cases of two patients admitted to our Unit due to severe hypoxemic failure needing very high oxygen flow.

First case: male, age 65, suffering from lung fibrosis, admitted in our RICU in January 2010. Second case: female, age 53, suffering from severe COPD (panlobular emphysema), admitted on december 2010.

Despite optimal medical treatment and respiratory therapist intervention, oxygen requirement remained very high in both cases (12-14 l/min). RR, ABG value and SaO2 improved during TTO as showed in Tables 1 and 2.

View this table:

Table 1. O2 therapy by mask





View this table:

Table 2. O2 therapy by TTO





We utilized a modified Seldinger procedure (SCOOP cathether) to perform TTO.

We didn't observe significant adverse events during the procedure and the follow-up (one year and 2 months respectively). Dyspnoea (Borg scale) and quality of life improved significantly. TTO should be considered as a safe and effective option in LTOT in a well-defined group of patients, in particular for those requiring high oxygen flow administration.
Transdermal iontophoretic delivery of apomorphine in patients improved by surfactant formulation pretreatment
Authors: G.L. Li, J.J. de Vries, T.J. van Steeg, H. van den Bussche, H.J. Maas, H.J.E.M. Reeuwijk, M. Danhof, J.A. Bouwstra, T. van Laar
Journal: Journal of Controlled Release (2004)
Developing and Using the <i>Guide to Community Preventive Services</i>: Lessons Learned About Evidence-Based Public Health
Authors: Peter A. Briss, Ross C. Brownson, Jonathan E. Fielding, Stephanie Zaza
Journal: Annual Review of Public Health (2004)

The Guide to Community Preventive Services (Community Guide) is being developed under the leadership of the independent, nonfederal Task Force on Community Preventive Services. The Task Force makes recommendations for the use of public health programs and policies based on scientific evidence about what practices have worked to improve health. The Community Guide thoroughly searches scientific literature for topic-relevant studies, evaluates their quality according to established criteria, and makes recommendations based on the overall strength of the body of evidence and the size and variability of reported effects. In addition, the Community Guide identifies promising interventions that have not been adequately researched, thus helping to inform the public health research agenda. The continuously updated and expanded body of recommendations and research agenda formulated by this rigorous process have been published on the Internet and in various publications since 1999 and constitute a highly valued and objective evidence-based resource for guiding current and future public health activities. More remains to be learned, however, on how best to disseminate Community Guide findings to key target audiences and encourage their use to inform practice, policy, and additional research.
Traitement Physique des Rhumatismes. Bases, Techniques, Indications
Authors: A. St. J. Dixon
Journal: Annals of the Rheumatic Diseases (1972)

Annals of the Rheumatic Diseases shared by 69 authors, and are divided into 70 chapters, most of which have a lengthy up-to-date (1969) list of references, surveying, unlike some North American productions, the European as well as the North and South American literature.Except for a few indifferent colour plates, it is well illustrated with diagrams and photographs and covers the same general field as the textbooks by Copeman and by Hollander.Of interest to
Inhibition of L-Type Ca <sup>2+</sup> Channel Current in Rat Ventricular Myocytes by Terfenadine
Authors: Shi Liu, Russell B. Melchert, Richard H. Kennedy
Journal: Circulation Research (1997)

To elucidate possible mechanisms underlying the cardiotoxicity of terfenadine, the effect of this antihistamine on L-type Ca2+ channel current (ICa,L) was studied in adult rat ventricular myocytes using the whole-cell patch-clamp technique. Myocytes were held at -70 mV and internally dialyzed and externally perfused with Na(+)- and K(+)-free solutions; exposure to terfenadine (10(-9) to 5 x 10(-6) mol/L) resulted in a concentration-dependent inhibition of peak ICa,L with a half-maximum inhibition concentration (IC50) of 142 nmol/L. The terfenadine-induced inhibition of ICa,L was not mediated via effects on histamine H1 receptors, because 1 mumol/L triprolidine, a more selective and potent H1 antagonist, had no effect on ICa,L. In this study, we found that terfenadine (1) increased both the fast and slow time constants of ICa,L inactivation, (2) shifted the steady state inactivation of ICa,L to more negative potentials, and (3) elicited a tonic block and a use-dependent block of ICa,L. The terfenadine-induced tonic and use-dependent block and the steady state inhibition of ICa,L were voltage dependent. Both tonic and use-dependent blocks of ICa,L by terfenadine at -40 mV were greater than that at -70 mV, and blocks were partially released by applying a long hyperpolarizing prepulse to -90 mV. These results suggest that terfenadine binds to L-type Ca2+ channels in inactivated and rested states and inhibits ICa,L predominantly by interacting with the inactivated state with an apparent dissociation constant of 60 nmol/L. Open-state block could be observed only at high concentrations of terfenadine. The high-affinity interaction of terfenadine with the inactivated state of L-type Ca2+ channels may play an important role in its cardiotoxicity under pathophysiological conditions, such as ischemia.
Acquired Resistance to BRAF Inhibitors Mediated by a RAF Kinase Switch in Melanoma Can Be Overcome by Cotargeting MEK and IGF-1R/PI3K
Authors: Jessie Villanueva, Adina Vultur, John T. Lee, Rajasekharan Somasundaram, Mizuho Fukunaga-Kalabis, Angela K. Cipolla, Bradley Wubbenhorst, Xiaowei Xu, Phyllis A. Gimotty, Damien Kee, Ademi E. Santiago-Walker, Richard Letrero, Kurt D'Andrea, Anitha Pushparajan, James E. Hayden, Kimberly Dahlman Brown, Sylvie Laquerre, Grant A. McArthur, Jeffrey A. Sosman, Katherine L. Nathanson, Meenhard Herlyn
Journal: Cancer Cell (2010)
Allergic disease is associated with epilepsy in childhood: a US population‐based study
Authors: J. I. Silverberg, R. Joks, H. G. Durkin
Journal: Allergy (2013)

Previous studies using animal models suggest an association between allergic disease and epilepsy. We sought to determine whether allergic disease is associated with epilepsy in children.We used the 2007-2008 National Survey of Children's Health, a US population-based study of 91 642 children aged 0-17 years to determine the association between the prevalence of epilepsy and allergic disease, including asthma, atopic dermatitis (AD)/eczema, hay fever, and food allergies. Multivariate logistic regression models were constructed that controlled for confounding variables.The US lifetime prevalence of childhood epilepsy was 1.03% and was significantly associated with older age, male sex, lower household income, family structure and history of brain injury or concussion. Children with ≥1 allergic disease had more epilepsy in their lifetime than nonallergic children (logistic regression, adjusted odds ratio [95% confidence interval] = 1.79 [1.37-2.33]). Lifetime prevalence (2.30 [1.50-3.52]) and one-year prevalence of asthma (2.00 [1.41-2.84]), AD/eczema (1.73 [1.17-2.56]), hay fever (1.93 [1.41-2.65]) and food allergies (2.69 [1.38-4.01]) were associated with increased odds of ever being diagnosed with epilepsy. Similar results were found for current history of epilepsy. Severe AD/eczema (3.89 [1.34-11.32]) [corrected] and hay fever (2.46 [1.11-5.41]) were associated with even higher odds of epilepsy compared with mild/moderate disease. As the number of allergic diseases increased, so did the odds of lifetime history and current history of epilepsy.The US prevalence of epilepsy is associated with allergic diseases in children. Further studies are needed to determine whether allergic inflammation contributes toward epileptogenesis.
Expression levels of HMGA2 in adipocytic tumors correlate with morphologic and cytogenetic subgroups
Authors: Hammurabi Bartuma, Ioannis Panagopoulos, Anna Collin, Domenico Trombetta, Henryk A Domanski, Nils Mandahl, Fredrik Mertens
Journal: Molecular Cancer (2009)

The HMGA2 gene encodes a protein that alters chromatin structure. Deregulation, typically through chromosomal rearrangements, of HMGA2 has an important role in the development of several mesenchymal neoplasms. These rearrangements result in the expression of a truncated protein lacking the acidic C-terminus, a fusion protein consisting of the AT-hook domains encoded by exons 1–3 and parts from another gene, or a full-length protein; loss of binding sites for regulatory microRNA molecules from the 3' untranslated region (UTR) of HMGA2 has been suggested to be a common denominator. Seventy adipocytic tumors, representing different morphologic and cytogenetic subgroups, were analyzed by qRT-PCR to study the expression status of HMGA2; 18 of these tumors were further examined by PCR to search for mutations or deletions in the 3'UTR. Type (full-length or truncated) and level of expression varied with morphology and karyotype, with the highest levels in atypical lipomatous tumors and lipomas with rearrangements of 12q13-15 and the lowest in lipomas with 6p- or 13q-rearrangements, hibernomas, spindle cell lipomas and myxoid liposarcomas. All 18 examined tumors showed reduced or absent expression of the entire, or parts of, the 3'UTR, which was not due to mutations at the DNA level. In adipocytic tumors with deregulated HMGA2 expression, the 3'UTR is consistently lost, either due to physical disruption of HMGA2 or a shift to production of shorter 3'UTR.
Pulmonary lymphangioleiomyomatosis: a report of 46 patients including a clinicopathologic study of prognostic factors.
Authors: M Kitaichi, K Nishimura, H Itoh, T Izumi
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The clinical and pathologic features of 46 patients from Japan, Korea, and Taiwan with pulmonary lymphangioleiomyomatosis (LAM) were studied. Only two (5%) among 40 evaluable treatments were assessed to be effective. Some prognostic factors of LAM were recognized. A reduction of the forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio was a poor prognostic factor at 2 yr after the first examination, with a statistically significant difference (p < 0.05). An increase in the percentage of predicted total lung capacity (%TLC) correlated with a poor prognosis at 2, 3, and 5 yr after the first examination, with statistically significant differences (p < 0.05). Histologically, two types of pulmonary lesions were observed; a predominantly cystic type and a predominantly muscular type. Patients with predominantly cystic LAM lesions showed a tendency to a poor prognosis from 2 to 5 yr after the biopsy. Among open lung biopsy findings, higher grades of abnormal areas were unfavorable as a prognostic factor from 2 to 5 yr after the biopsy, with statistically significant differences (p < 0.05). Higher grades of cystic lesions correlated inversely with survival at 2, 4, and 5 yr after the lung biopsy, with statistically significant differences (p < 0.05).
An unexpected role for the anaphylatoxin C5a receptor in allergic sensitization
Authors: B. N. Lambrecht
Journal: Journal of Clinical Investigation (2006)

The anaphylatoxins complement component 3a and 5a (C3a and C5a, respectively) are classically seen as proinflammatory mediators of allergic asthma that recruit inflammatory cells, induce edema, and cause bronchoconstriction. A few years ago, controversy arose when it was shown that C5-deficient mice were more susceptible to experimental asthma compared with C5-sufficient mice. In a study by Köhl et al. in this issue of the JCI, it is shown in a series of truly "complementary" experiments that C5a receptor (C5aR) blockade promotes Th2 sensitization upon first exposure to inhaled allergen, whereas C5aR blockade during established inflammation suppresses the cardinal features of asthma (see the related article beginning on page 783). Blockade of C5aR alters the function of airway DCs, crucial for inducing and maintaining Th2 responses in the lung. Targeting C5aR as a treatment for established asthma could be beneficial, but might be accompanied by sensitization to novel antigens.
The Persistence of Hepatitis A IgM Antibody After Acute Clinical Hepatitis A
Authors: Henry W. Kao, Mary Ashcavai, Allan G. Redeker
Journal: Hepatology (1984)

Hepatitis A IgM antibody (IgM anti-HAV), detected by commercially available solid-phase radioimmunoassay, is an accepted marker of acute viral hepatitis A infection. However, persistence of this serological marker far beyond the acute illness and immediate convalescent period has been reported. To determine the persistence of IgM anti-HAV following clinically manifest acute hepatitis A infection, 59 patients with this diagnosis were followed prospectively until this marker disappeared or persisted for greater than 60 days. Timed from the onset of jaundice, IgM anti-HAV persisted for less than 30 to greater than 420 days; most patients became seronegative by 120 days. These findings suggest that some patients may become seronegative early in the disease course while others (13.5%) remain positive for prolonged periods greater than 200 days. Awareness of this marked variability is important in the interpretation of IgM anti-HAV as a serologic marker of recent hepatitis A infection.
Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891
Authors: J.-L. Lefebvre, G. Andry, D. Chevalier, B. Luboinski, L. Collette, L. Traissac, D. de Raucourt, J.A. Langendijk
Journal: Annals of Oncology (2012)
Association Between Colonoscopy and Colorectal Cancer Mortality in a US Cohort According to Site of Cancer and Colonoscopist Specialty
Authors: Nancy N. Baxter, Joan L. Warren, Michael J. Barrett, Therese A. Stukel, V. Paul Doria-Rose
Journal: Journal of Clinical Oncology (2012)

Purpose We designed this study to evaluate the association of colonoscopy with colorectal cancer (CRC) death in the United States by site of CRC and endoscopist specialty. Methods We designed a case-control study using Surveillance, Epidemiology, and End Results (SEER)–Medicare data. We identified patients (cases) diagnosed with CRC age 70 to 89 years from January 1998 through December 2002 who died as a result of CRC by 2007. We selected three matched controls without cancer for each case. Controls were assigned a referent date (date of diagnosis of the case). Colonoscopy performed from January 1991 through 6 months before the diagnosis/referent date was our primary exposure. We compared exposure to colonoscopy in cases and controls by using conditional logistic regression controlling for covariates, stratified by site of CRC. We determined endoscopist specialty by linkage to the American Medical Association (AMA) Masterfile. We assessed whether the association between colonoscopy and CRC death varied with endoscopist specialty. Results We identified 9,458 cases (3,963 proximal [41.9%], 4,685 distal [49.5%], and 810 unknown site [8.6%]) and 27,641 controls. In all, 11.3% of cases and 23.7% of controls underwent colonoscopy more than 6 months before diagnosis. Compared with controls, cases were less likely to have undergone colonoscopy (odds ratio [OR], 0.40; 95% CI, 0.37 to 0.43); the association was stronger for distal (OR, 0.24; 95% CI, 0.21 to 0.27) than proximal (OR, 0.58; 95% CI, 0.53 to 0.64) CRC. The strength of the association varied with endoscopist specialty. Conclusion Colonoscopy is associated with a reduced risk of death from CRC, with the association considerably and consistently stronger for distal versus proximal CRC. The overall association was strongest if colonoscopy was performed by a gastroenterologist.