tbuckley/cabot-search huggingface dataset:
Recommendations for the management of autoinflammatory diseases
Authors: Nienke M ter Haar, Marlen Oswald, Jerold Jeyaratnam, Jordi Anton, Karyl S Barron, Paul A Brogan, Luca Cantarini, Caroline Galeotti, Gilles Grateau, Veronique Hentgen, Michael Hofer, Tilmann Kallinich, Isabelle Kone-Paut, Helen J Lachmann, Huri Ozdogan, Seza Ozen, Ricardo Russo, Anna Simon, Yosef Uziel, Carine Wouters, Brian M Feldman, Sebastiaan J Vastert, Nico M Wulffraat, Susanne M Benseler, Joost Frenkel, Marco Gattorno, Jasmin B Kuemmerle-Deschner
Journal: Annals of the Rheumatic Diseases (2015)

: Autoinflammatory diseases are characterised by fever and systemic inflammation, with potentially serious complications. Owing to the rarity of these diseases, evidence-based guidelines are lacking. In 2012, the European project Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate regimens for the management of children and young adults with rheumatic diseases, facilitating the clinical practice of paediatricians and (paediatric) rheumatologists. One of the aims of SHARE was to provide evidence-based recommendations for the management of the autoinflammatory diseases cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and mevalonate kinase deficiency (MKD). These recommendations were developed using the European League Against Rheumatism standard operating procedure. An expert committee of paediatric and adult rheumatologists was convened. Recommendations derived from the systematic literature review were evaluated by an online survey and subsequently discussed at a consensus meeting using Nominal Group Technique. Recommendations were accepted if more than 80% agreement was reached. In total, four overarching principles, 20 recommendations on therapy and 14 recommendations on monitoring were accepted with ≥80% agreement among the experts. Topics included (but were not limited to) validated disease activity scores, therapy and items to assess in monitoring of a patient. By developing these recommendations, we aim to optimise the management of patients with CAPS, TRAPS and MKD.
Prognostic effect of the variable course of alcoholism on the 10-year course of depression
Authors: T I Mueller, P W Lavori, M B Keller, A Swartz, M Warshaw, D Hasin, W Coryell, J Endicott, J Rice, H Akiskal
Journal: American Journal of Psychiatry (1994)

The purpose of this study was to examine the predictive effect of the clinical activity of patients' alcohol use on the course of major depressive disorder.One hundred seventy-six probands with Research Diagnostic Criteria (RDC) diagnoses of both major depressive disorder and alcoholism were compared to 412 probands with major depressive disorder only by using 10 years of short-interval, prospective follow-up data collected as part of the National Institute of Mental Health Collaborative Depression Study. The course of depression was examined by using intensity analysis to represent transitions between states of major depressive disorder. The effect of patients' RDC alcoholism status on the long-term course of major depressive disorder was examined by stratifying the analyses by three levels of alcoholism--never alcoholic, not meeting criteria for current alcoholism, and current alcoholism.Depressed probands who were either never alcoholic or currently nonactive alcoholic had twice the likelihood of recovery from major depressive disorder than did actively alcoholic depressed probands. The three levels of alcoholism did not differentially predict recurrence of major depressive disorder.These findings provide long-term, empirically derived evidence for the deleterious effect of current alcoholism on recovery from depression. The lack of a differential effect of the three levels of alcoholism on recurrence of major depressive disorder suggests that other factors may have greater predictive value.
Topical treatment of actinic keratoses with 3·0% diclofenac in 2·5% hyaluronan gel
Authors: J.K. Rivers, J. Arlette, N. Shear, L. Guenther, W. Carey, Y. Poulin
Journal: British Journal of Dermatology (2002)

Actinic keratoses (AKs) are premalignant skin lesions, which, if left untreated, can develop into squamous cell carcinoma. Current treatments for AKs are destructive and are often associated with significant adverse events. The development of an effective and well-tolerated topical treatment for AK is desirable.To evaluate the efficacy and safety of 3.0% diclofenac in 2.5% hyaluronan gel as a treatment for AK.This was a multicentre, double-blind, placebo-controlled study in which 195 patients with at least five AKs in up to three designated treatment blocks were randomized to four treatment groups. Patients randomized into the active treatment groups A30 (n = 49) and A60 (n = 48) received topical treatment with 3.0% diclofenac in 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Patients in the placebo (vehicle gel) groups V30 (n = 49) and V60 (n = 49) received topical treatment with 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Treatment efficacy was assessed by target and cumulative lesion number scores (TLNS and CLNS, respectively) and lesion total thickness score (TTS). Investigator and patient global improvement indices (IGII and PGII) were also used to rate overall improvement.Compared with placebo, significantly more patients given active treatment for 60 days had TLNS = 0 (33% vs. 10%, P < 0.05; an improvement of 64% compared with 34% with placebo), CLNS = 0 (31% vs. 8%, P < 0.05; an improvement of 54% compared with 23% with placebo) and TTS = 0 (25% vs. 6%, P < 0.05; an improvement of 59% compared with 31% with placebo). The IGII and PGII scores were also significantly better when active treatment was compared with placebo (P < 0.05). Both treatments were generally well tolerated and the incidence of the most common adverse events was similar between groups.Treatment with 3.0% diclofenac in 2.5% hyaluronan gel was effective when used for 60 days and was well tolerated in patients with AK.
Segment-Specific c-ErbB2 Expression in Human Autosomal Recessive Polycystic Kidney Disease
Authors: KOICHI NAKANISHI, WILLIAM E. SWEENEY, ELLIS D. AVNER
Journal: Journal of the American Society of Nephrology (2001)

Abstract. c-ErbB2 (also referred to as Neu or HER2), a transmembrane glycoprotein with intrinsic tyrosine kinase activity, is structurally related to epidermal growth factor receptor (EGFR) and forms active heterodimers with EGFR as well as other members of the EGFR family. c-ErbB2 is reported to mediate differentiation and proliferation in epithelial cells and is expressed in a tissue-specific and developmental stage-specific manner. Given the role of EGFR in cystic renal epithelial hyperplasia and the immature phenotype of cystic renal epithelial cells, the segment-specific expression pattern of c-ErbB2 in human autosomal recessive polycystic kidney disease (ARPKD) was examined in nine ARPKD kidney specimens ranging from gestational age 17 wk through postnatal age 4 wk. c-ErbB2 staining of human ARPKD samples showed increased expression with increasing gestational age compared with normal human fetal and postnatal kidneys. This increased c-ErbB2 expression was primarily localized to the apical surfaces of cystic collecting tubule cells, similar to the pattern of EGFR expression, and paralleled collecting tubular cyst formation and growth.
Enhancing the discovery and development of immunotherapies for cancer using quantitative and systems pharmacology: Interleukin-12 as a case study
Authors: David J Klinke
Journal: Journal for ImmunoTherapy of Cancer (2015)

Recent clinical successes of immune checkpoint modulators have unleashed a wave of enthusiasm associated with cancer immunotherapy. However, this enthusiasm is dampened by persistent translational hurdles associated with cancer immunotherapy that mirror the broader pharmaceutical industry. Specifically, the challenges associated with drug discovery and development stem from an incomplete understanding of the biological mechanisms in humans that are targeted by a potential drug and the financial implications of clinical failures. Sustaining progress in expanding the clinical benefit provided by cancer immunotherapy requires reliably identifying new mechanisms of action. Along these lines, quantitative and systems pharmacology (QSP) has been proposed as a means to invigorate the drug discovery and development process. In this review, I discuss two central themes of QSP as applied in the context of cancer immunotherapy. The first theme focuses on a network-centric view of biology as a contrast to a "one-gene, one-receptor, one-mechanism" paradigm prevalent in contemporary drug discovery and development. This theme has been enabled by the advances in wet-lab capabilities to assay biological systems at increasing breadth and resolution. The second theme focuses on integrating mechanistic modeling and simulation with quantitative wet-lab studies. Drawing from recent QSP examples, large-scale mechanistic models that integrate phenotypic signaling-, cellular-, and tissue-level behaviors have the potential to lower many of the translational hurdles associated with cancer immunotherapy. These include prioritizing immunotherapies, developing mechanistic biomarkers that stratify patient populations and that reflect the underlying strength and dynamics of a protective host immune response, and facilitate explicit sharing of our understanding of the underlying biology using mechanistic models as vehicles for dialogue. However, creating such models require a modular approach that assumes that the biological networks remain similar in health and disease. As oncogenesis is associated with re-wiring of these biological networks, I also describe an approach that combines mechanistic modeling with quantitative wet-lab experiments to identify ways in which malignant cells alter these networks, using Interleukin-12 as an example. Collectively, QSP represents a new holistic approach that may have profound implications for how translational science is performed.
A field trial of DSM-III-R psychoactive substance dependence disorders
Authors: B J Rounsaville, T R Kosten, J B Williams, R L Spitzer
Journal: American Journal of Psychiatry (1987)

The authors field-tested proposed criteria for diagnoses of psychoactive substance use disorders in the revision of DSM-III (DSM-III-R) and compared them with DSM-III criteria in a treated group of 83 patients. They found a high level of agreement between the diagnostic systems in rates of diagnosis and in the individuals receiving the diagnosis. The greatest cross-system agreement occurred when the minimum number of symptoms required to make the DSM-III-R diagnosis was set at three. Discrepant diagnoses between systems related to removal of social consequences as a requirement for the DSM-III-R diagnoses, less emphasis on physiological tolerance in DSM-III-R, and disagreement in subjects with mild symptoms.
Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle–Aged Adults at Risk for Alzheimer Disease
Authors: Auriel A. Willette, Barbara B. Bendlin, Erika J. Starks, Alex C. Birdsill, Sterling C. Johnson, Bradley T. Christian, Ozioma C. Okonkwo, Asenath La Rue, Bruce P. Hermann, Rebecca L. Koscik, Erin M. Jonaitis, Mark A. Sager, Sanjay Asthana
Journal: JAMA Neurology (2015)

Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET).To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance.This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD parental history. Participants underwent cognitive testing, fasting blood draw, and FDG-PET at baseline. We used the homeostatic model assessment of peripheral insulin resistance (HOMA-IR). Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to determine whether HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, apolipoprotein E ε4 genotype, AD parental history status, and a reference region used to normalize regional uptake.Regional glucose uptake determined using FDG-PET and neuropsychological factors.Higher HOMA-IR was associated with lower global glucose metabolism (β = -0.29; P < .01) and lower regional glucose metabolism across large portions of the frontal, lateral parietal, lateral temporal, and medial temporal lobes (P < .05, familywise error corrected). The association was especially robust in the left medial temporal lobe (R2 = 0.178). Lower glucose metabolism in the left medial temporal lobe predicted by HOMA-IR was significantly related to worse performance on the immediate memory (β = 0.317; t148 = 4.08; P < .001) and delayed memory (β = 0.305; t148 = 3.895; P < .001) factor scores.Our results show that insulin resistance, a prevalent and increasingly common condition in developed countries, is associated with significantly lower regional cerebral glucose metabolism, which in turn may predict worse memory performance. Midlife may be a critical period for initiating treatments to lower peripheral insulin resistance to maintain neural metabolism and cognitive function.
Differences in the proportions of fluoroquinolone-resistant Gram-negative bacteria isolated from bacteraemic children with cancer in two Italian centres
Authors: E. Castagnola, R. Haupt, A. Micozzi, I. Caviglia, A.M. Testi, F. Giona, S. Parodi, C. Girmenia
Journal: Clinical Microbiology and Infection (2005)
Lymphoreticular Tumors and Leukemias in Egypt&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: P. Correa, G. T. O'Conor, A. Lotfy Aboul Nasr, Hassan Nabil Tawfik, Moustafa Abu El-Einen
Journal: JNCI Journal of the National Cancer Institute (1973)

Malignant lymphomas have been reported to constitute from 11.8% to 15.9% of all malignant tumors in the large medical centers, in Egypt. In the present study, the age, sex, and type distribution in 557 cases-of malignant lymphomas is reported. Reticulum cell sarcoma was the most frequent type, followed by Hodgkin's disease and then lymphosarcoma. Reticulum cell sarcoma and lymphosarcoma had a similar age distribution-being rare in children and rising sharply in frequency after age 30 years in males and a decade later in females. The male/female ratio was 2:1 and 2.6:1, respectively. Hodgkin's disease showed an age peak in the second decade and a male/female ratio of 3:1. Mixed cellularity was the most common subtype and nodular sclerosis the rarest. Of 178 cases of leukemia, 76 were acute and 102 chronic. The age, sex, and type distribution is presented.
Rituximab–cyclophosphamide‐dexamethasone is highly effective in patients with monoclonal <scp>I</scp>g deposit‐related glomerulopathy and indolent non‐<scp>H</scp>odgkin lymphomas
Authors: Marielle Perry, Antoine Delarche, David Ribes, François Vergez, Céline Guilbeau‐Frugier, Camille Laurent, Antoine Huart, Suzanne Tavitian, Hélène El Hachem, Lucie Oberic, Dominique Chauveau, Anne‐Sophie Michallet, Loïc Ysebaert, Stanislas Faguer
Journal: American Journal of Hematology (2014)

Indolent non-hodgkin lymphomas (iNHL) are a rare cause of monoclonal immunoglobulin deposits-related glomerulopathy (mIgGN). In patients with iNHL-related mIgGN, whether treatment should include either single or a combination of drug(s) to target the malignant clone and renal inflammation remains elusive. In this retrospective study, we report a cohort of 14 patients with iNHL-related mIgGN (cryoglobulinemic glomerulonephritis [n = 5], membranous nephropathy [n = 3], membranoproliferative glomerulonephritis [n = 3], AL or AL/AH amyloidosis [n = 2], and Light Chain Deposits Disease [n = 1]) and who received a treatment combining rituximab, cyclophosphamide, and dexamethasone (RCD). After a mean follow-up of 18 ± 4 months, nine patients (63%) had complete haematological response. Renal response was observed in 12 of the 14 patients (86%; complete response: n = 9; partial: n = 3). Estimated glomerular filtration rate increased from 47 ± 7 to 63 ± 8 mL/min/1.73 m(2) , and proteinuria decreased from 6.5 ± 0.7 to 1.4 ± 0.8 g/24 hr at one year. Following hematological relapse, renal relapse occurred in two patients suggesting sustained clonal eradication offers the best renal protection. Tolerance of RCD was good and the most frequent adverse event was pneumonia (3/14, 21%). RCD is a promising regimen for patients with iNHL and mIgGN, irrespective of glomerular pathologic pattern. Whether steroids can be avoided or minimized remains to be addressed.
The role of endothelial cell apoptosis in the effect of etanercept in psoriasis
Authors: G. Avramidis, S. Krüger-Krasagakis, K. Krasagakis, I. Fragiadaki, G. Kokolakis, A. Tosca
Journal: British Journal of Dermatology (2010)

Psoriasis is a chronic inflammatory skin disease associated with abnormal vascular expansion in the papillary dermis. Tumour necrosis factor (TNF)-α is a proinflammatory cytokine that can induce antiapoptotic proteins and endothelial cell activation factors in psoriasis.The present study investigated the effect of the anti-TNF-α agent etanercept on the expression of endothelial nuclear factor-κB (NF-κB), angiogenic vascular endothelial growth factor (VEGF), endothelial cell marker CD31, antiangiogenic factor thrombospondin-1 (TSP-1), and antiapoptotic factors Bcl-2 and Bcl-xL in psoriasis.Sixteen patients with moderate-to-severe psoriasis were included in the study and treated with etanercept 50 mg twice weekly subcutaneously for 12 weeks. Biopsies of lesional skin (baseline, weeks 3, 6 and 10) were obtained and immunohistochemically stained with antibodies for CD31, VEGF, TSP-1, NF-κB, Bcl-2 and Bcl-xL. Double immunofluorescence staining for VEGF and CD31 was evaluated with confocal laser microscopy. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay was applied for apoptosis detection.Etanercept caused a statistically significant time-dependent reduction in the number of dermal blood vessels, the number of CD31+ cells and VEGF in psoriatic lesions, with induction of endothelial cell apoptosis and statistically significant upregulation of TSP-1 in psoriatic vessels. Immunohistochemical analysis showed significant reduction of NF-κB, Bcl-2 and Bcl-xL expression in endothelial cells during treatment. These changes were accompanied by a marked clinical response.The present findings suggest that treatment with etanercept induces apoptosis, reduces apoptosis-inhibiting factors in psoriatic endothelial cells, and decreases angiogenesis in psoriatic skin.
Kinetics of Effect of 1-β-&lt;sc&gt;D&lt;/sc&gt;-Arabinofuranosylcytosine, Its 5′-Palmitoyl Ester, 1-β-&lt;sc&gt;D&lt;/sc&gt;-Arabinofuranosyluracil, and Tritiated Thymidine on the Viability of Cultured Leukemia L1210 Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Lee J. Wilkoff, Elizabeth A. Dulmadge, Harris H. Lloyd
Journal: JNCI Journal of the National Cancer Institute (1972)
Effects of Danazol on Mineral Homeostasis in Normal Postmenopausal Women: Preliminary Communication
Authors: D W Purdie, A Hay, S K Abbas
Journal: Journal of the Royal Society of Medicine (1987)

The effects of danazol on calcium homeostasis in normal postmenopausal women was examined in a 14-day study utilizing a dosage of 800 mg per day. Danazol caused significant falls in plasma ionized calcium and in the fasting urinary calcium/creatinine ratio, indicating inhibition of bone resorption. Retention of phosphate was also observed as expected with this anabolic agent. The plasma total alkaline phosphatase was also depressed by the drug, which had no effect on hepatocellular function as measured by plasma AST. Certain effects induced by treatment with danazol were still apparent two weeks after cessation of treatment. The drug was well tolerated and androgenic side effects were not seen. It is suggested that the minimal dose regimen of danazol which exerts a calcium-sharing effect should be identified, and that this regimen should be considered for use in a prospective study of the effects of danazol on bone mineral content in the postmenopause.
Resistance of problematic gram(-) respiratory pathogens selected from in-patients (Yaroslavl, Russia, 2011)
Authors: Shamil Palyutin, Ilya Zilber, Svetlana Monakhova, Svetlana Angelova, Marina Ershova, Galina Abrosimova, Elena Poletaeva, Alexander Petrochenko
Journal: European Respiratory Journal (2012)

Backgound: the problem of the spread of resistant Gram(-) agents becomes more urgent. These changes in the respiratory pathogens in hospitals create difficulties in antibiotic therapy and lead to increase of patients9 lethality and the burden for general healthcare.  The aim of our study was to assess the prevalence of resistance of the problematic Gram(-) pathogens in hospitalized patients.  Methods: pathogens were isolated from hospitalized patients in Yaroslavl. The selection of pathogens and the determination of resistance was performed centrally in the microbiological laboratory (NCCLS standards, disc-diffusion method).  Results: in 2011 in the city9s hospitals 98 strains of  Ps. aeruginosae , 71 -  Acinetobacter  spp were allocated from respiratory tract in hospitalized patients. Resistance of  Ps. aeruginosae  was extremely high practically to all drugs, including carbapenems. The only exception was polymyxin (all strains were sensitive). The average rate of resistance was 39.2%. Resistance  Ps. aeruginosae  to piperacillin/tazobactam, cefoperasone/sulbactam, imipenem, meropenem, ciproflocacin, gentamycin, amikacin was 51, 48, 48, 49, 54, 47 and 48% respectively. At a relatively acceptable level there was observed resistance to ceftazidime, cefepime and aztreonam - 16, 23, and 15% respectively.  Acinetobacter  spp. also showed a high resistance (in average of 61.9%). Carbapenems remained active (imipenem - 99% of strains were sensitive, meropenem - 94%).  Conclusions: the problematic respiratory Gram(-) pathogens as  Ps. aeruginosae  and  Acinetobacter  spp. show high resistance to antimicrobial agents. The greatest concern is the resistance to carbapenems in  Pseudomonas aeruginosa .