tbuckley/cabot-search huggingface dataset:
Treatment of rheumatoid arthritis with PEGylated recombinant human soluble tumour necrosis factor receptor type I: a clinical update
Authors: M. W Davis
Journal: Annals of the Rheumatic Diseases (2000)

<h3>Background</h3> 52-week results from C-axSpAnd demonstrated the safety and efficacy of certolizumab pegol (CZP) in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) and objective signs of inflammation (sacroiliitis on MRI and/or elevated C-reactive protein levels). Long-term safety and clinical outcomes, including MRI assessments, are evaluated up to 3 years for CZP-treated patients with nr-axSpA. <h3>Methods</h3> C-axSpAnd was a phase 3 study comprising a 1-year double-blind, placebo-controlled period and 2-year open-label safety follow-up extension (SFE). At baseline, 317 patients were randomised 1:1 to placebo or CZP 200 mg every 2 weeks. Patients completing the double-blind phase who enrolled into the SFE received open-label CZP for an additional 104 weeks. Long-term safety and clinical outcomes are reported to Week 156. Continuous outcomes are presented as observed case (OC) and dichotomous outcomes as OC and with non-responder imputation. <h3>Results</h3> 243/317 (76.7%) patients entered the SFE, during which 149 (61.3%) experienced ≥1 treatment-emergent adverse event (TEAE); 15 (3.3/100 patient-years) experienced serious TEAEs. Continuous outcome scores (including Ankylosing Spondylitis Disease Activity Score [ASDAS]: 1.8; Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]: 2.7) at Week 52 were maintained at Week 156 (ASDAS: 1.8; BASDAI: 2.6) for the initial CZP-randomised group. Mean SPARCC MRI sacroiliac joint inflammation scores for these patients decreased at Week 52 (baseline: 7.6; Week 52: 1.7), remaining low at Week 156 (2.4). <h3>Conclusions</h3> CZP treatment was well tolerated up to 3 years, with no new safety signals versus previous reports. Clinical outcomes achieved after 1 year were sustained to 3 years. <h3>Trial registration number</h3> NCT02552212.
Parental history of lupus and rheumatoid arthritis and risk in offspring in a nationwide cohort study: does sex matter?
Authors: Emily C Somers, Sussie Antonsen, Lars Pedersen, Henrik Toft Sørensen
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To examine the familial risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), including juvenile rheumatoid/idiopathic arthritis (JRA), in a population-based setting; and to determine whether patterns of transmission differ according to the sex of the parent or offspring, in order to provide insight into the potential impact of X-chromosomal factors on sex disparities in these autoimmune diseases. <h3>Methods</h3> A population-based cohort of parent–offspring triads from Denmark (1977–2010) was established. SLE and RA incidence rates among offspring were calculated, and Cox regression was performed to assess the sex-specific risk of disease in offspring according to maternal or paternal disease history. <h3>Results</h3> Among 3 513 817 parent–offspring triads, there were 1258 SLE cases among offspring (1095 female, 163 male) and 9118 cases of RA/JRA (6086 female, 3032 male). Among female offspring, SLE risk was nearly the same according to maternal (HR 14.1) or paternal (HR 14.5) history (p=NS); likewise among male offspring, risk according to maternal (HR 5.5) and paternal (no cases) history were similar (p=NS). For RA, all risk estimates were similar, regardless of the sex of the offspring or parent (HR 2.6–2.9; p=NS). <h3>Conclusions</h3> The authors quantified the familial risk of SLE and RA in a nationwide cohort study. For both diseases, transmission was comparable among both female and male offspring of maternal and paternal cases. These data provide evidence at the population level that X-chromosomal factors do not play a major role in sex disparities associated with the risk of SLE and RA.
On the Duration of the Quarantine Required after Puerperal Fever
Authors: J. B. Hicks
Journal: BMJ (1876)

IN the Medico-Chirurgical Transactions for 1872, vol.55, will be found some particulars of, I believe, an unique case, in which, during the war of I870-7I, I performed resection of the shoulder-and elbow-joints in the same arm.The patient, a man called St. Aubin, was one of the corps Chasseurs d'Afrique, the third regiment of which took an active part in the battle of Sedan, under the command of the Marquis de Galliffet.
Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy
Authors: Moniek G.P.J. Cox, Paul A. van der Zwaag, Christian van der Werf, Jasper J. van der Smagt, Maartje Noorman, Zahir A. Bhuiyan, Ans C.P. Wiesfeld, Paul G.A. Volders, Irene M. van Langen, Douwe E. Atsma, Dennis Dooijes, Arthur van den Wijngaard, Arjan C. Houweling, Jan D.H. Jongbloed, Luc Jordaens, Maarten J. Cramer, Pieter A. Doevendans, Jacques M.T. de Bakker, Arthur A.M. Wilde, J. Peter van Tintelen, Richard N.W. Hauer
Journal: Circulation (2011)

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an autosomal dominant inherited disease with incomplete penetrance and variable expression. Causative mutations in genes encoding 5 desmosomal proteins are found in ≈50% of ARVD/C index patients. Previous genotype-phenotype relation studies involved mainly overt ARVD/C index patients, so follow-up data on relatives are scarce.One hundred forty-nine ARVD/C index patients (111 male patients; age, 49±13 years) according to 2010 Task Force criteria and 302 relatives from 93 families (282 asymptomatic; 135 male patients; age, 44±13 years) were clinically and genetically characterized. DNA analysis comprised sequencing of plakophilin-2 (PKP2), desmocollin-2, desmoglein-2, desmoplakin, and plakoglobin and multiplex ligation-dependent probe amplification to identify large deletions in PKP2. Pathogenic mutations were found in 87 index patients (58%), mainly truncating PKP2 mutations, including 3 cases with multiple mutations. Multiplex ligation-dependent probe amplification revealed 3 PKP2 exon deletions. ARVD/C was diagnosed in 31% of initially asymptomatic mutation-carrying relatives and 5% of initially asymptomatic relatives of index patients without mutation. Prolonged terminal activation duration was observed more than negative T waves in V(1) to V(3), especially in mutation-carrying relatives <20 years of age. In 45% of screened families, ≥1 affected relatives were identified (90% with mutations).Pathogenic desmosomal gene mutations, mainly truncating PKP2 mutations, underlie ARVD/C in the majority (58%) of Dutch index patients and even 90% of familial cases. Additional multiplex ligation-dependent probe amplification analysis contributed to discovering pathogenic mutations underlying ARVD/C. Discovering pathogenic mutations in index patients enables those relatives who have a 6-fold increased risk of ARVD/C diagnosis to be identified. Prolonged terminal activation duration seems to be a first sign of ARVD/C in young asymptomatic relatives.
Faecal unconjugated bile acids in patients with colorectal cancer or polyps.
Authors: C H Imray, S Radley, A Davis, G Barker, C W Hendrickse, I A Donovan, A M Lawson, P R Baker, J P Neoptolemos
Journal: Gut (1992)

The authors investigate the biases in the backtested performance of "alternative beta" strategies using a unique sample of 215 trading strategies developed and promoted by global investment banks. Their results lend support to the cautions in the recent literature regarding backtest overfitting and lack of robustness in trading strategy performance during the "live" period (out of sample). The authors report a median 73% deterioration in Sharpe ratios between backtested and live performance periods for the strategies, and they establish a link between performance deterioration and strategy complexity, with the realized reduction in live versus backtested Sharpe ratios of the most complex strategies exceeding those of the simplest ones by over 30 percentage points. The robustness of strategy exposure to risk factors varies between asset classes and strategies; it appears reasonable in equity volatility and FX carry strategies but quite weak in the equity value strategy in particular. <b>TOPICS:</b>Analysis of individual factors/risk premia, performance measurement
Research of an arterial rigidity in patients with bronchial asthma and accompanying arterial hypertension and BMI
Authors: Elena Sobko, Angelina Kraposhina, Irina Soloveva, Svetlana Chubarova, Irina Demko
Journal: European Respiratory Journal (2014)

Research objective: to study an arterial rigidity depending on accompanying arterial hypertension and BMI in patients with bronchial asthma. We estimated parametres of rigidity of an aorta by means of an indirect arteriography (TensioMed, Hungary). Patients were divided into 2 groups to specify impact of arterial hypertension on bronchial asthma progression. The 1st group included 95 patients with bronchial asthma and arterial hypertension, women – 74 (77,8±4,3%); men – 21(22,2±4,3%); median of age 53 [48; 57] years. 105 people are included in the 2nd group, without an arterial hypertension, women – 74 (70,5±4,4%); men – 31(29,5±4,4%); median of age 41[30; 49] year. We have shown that in the 1st group changes of Pulse Wave Velocity (PWVao) and augmentation index (AIx) were more significant than in patients without arterial hypertension. At the same time, the rising of PWVao was observed in both groups in comparison with control whereas the AIx statistically significantly exceeded values of control only in group of patients with bronchial asthma and an arterial hypertension (p   25 kg/sq.m on an arterial rigidity. We found that when BMI is higher than 25 kg/sq.m development of an arterial rigidity in patients with asthma is promoted (elevation of AIx(-33[-49,8; -10,1]) and PWVao (9,1[7,4; 12]) in comparison with AIx parameters (-46,5[-62,6; -23,9]) and PWVao (7,3[6,5; 9,8]) in patients with normal BMI (p=0,002 and p 25 kg/sq.m.
Determinants of antegrade echo zone in the Wolff-Parkinson-White syndrome.
Authors: E L Pritchett, J J Gallagher, M Scheinman, W M Smith
Journal: Circulation (1978)

Forty-five patients with the Wolff-Parkinson-White syndrome and reciprocating tachycardia which utilized the atrioventricular (A-V) node for antegrade conduction and an accessory pathway for ventriculo-atrial (retrograde) conduction were studied. The extrastimulus technique in the right atrium and coronary sinus at multiple pacing cycle lengths was used. Three types of "echo zones" were defined by the relationship of the antegrade effective refractory period (ERP) of the accessory pathway, the longest coupling interval accompanied by an atrial echo, the ERP of the A-V node, and the functional refractory period of the atrium. Eighteen of 45 patients (40%) had more than one type of echo zone demonstrated by changing either pacing site or pacing cycle length or both. Pacing site and intraventricular conduction delay were found to have important effects on the longest coupling interval accompanied by an atrial echo in those echo zones in which the longest coupling interval accompanied by an atrial echo was less than the antegrade ERP of the accessory pathway. The echo zone is a useful concept to explain the physiology of the common reciprocating tachycardia in patients with the Wolff-Parkinson-White syndrome. However, the echo zone is profoundly affected by pacing site and pacing cycle length. When these variables are changed, many patients can be shown to have more than one type of echo zone. Studies of the echo zone have limited value as therapeutic guides.
Selective Toxicity of NSC73306 in MDR1-Positive Cells as a New Strategy to Circumvent Multidrug Resistance in Cancer
Authors: Joseph A. Ludwig, Gergely Szakács, Scott E. Martin, Benjamin F. Chu, Carol Cardarelli, Zuben E. Sauna, Natasha J. Caplen, Henry M. Fales, Suresh V. Ambudkar, John N. Weinstein, Michael M. Gottesman
Journal: Cancer Research (2006)

Abstract ATP-binding cassette (ABC) proteins include the best known mediators of resistance to anticancer drugs. In particular, ABCB1 [MDR1/P-glycoprotein (P-gp)] extrudes many types of drugs from cancer cells, thereby conferring resistance to those agents. Attempts to overcome P-gp-mediated drug resistance using specific inhibitors of P-gp has had limited success and has faced many therapeutic challenges. As an alternative approach to using P-gp inhibitors, we characterize a thiosemicarbazone derivative (NSC73306) identified in a generic screen as a compound that exploits, rather than suppresses, P-gp function to induce cytotoxicity. Cytotoxic activity of NSC73306 was evaluated in vitro using human epidermoid, ovarian, and colon cancer cell lines expressing various levels of P-gp. Our findings suggest that cells become hypersensitive to NSC73306 in proportion to the increased P-gp function and multidrug resistance (MDR). Abrogation of both sensitivity to NSC73306 and resistance to P-gp substrate anticancer agents occurred with specific inhibition of P-gp function using either a P-gp inhibitor (PSC833, XR9576) or RNA interference, suggesting that cytotoxicity was linked to MDR1 function, not to other, nonspecific factors arising during the generation of resistant or transfected cells. Molecular characterization of cells selected for resistance to NSC73306 revealed loss of P-gp expression and consequent loss of the MDR phenotype. Although hypersensitivity to NSC73306 required functional expression of P-gp, biochemical assays revealed no direct interaction between NSC73306 and P-gp. This article shows that NSC73306 kills cells with intrinsic or acquired P-gp-induced MDR and indirectly acts to eliminate resistance to MDR1 substrates. (Cancer Res 2006; 66(9): 4808-15)
216 DEVELOPMENT AND VALIDATION OF PELTQL: A DISEASE-SPECIFIC QUESTIONNAIRE TO MEASURE HEALTH-RELATED QUALITY OF LIFE IN PAEDIATRIC LIVER TRANSPLANT RECIPIENTS
Authors: V.L. Ng, P. Andreou, A. Dhawan, N. Yazigi, M.O. Stormon, L.C. Ee, S.M. Gilmour, D. Nicholas, A.R. Otley
Journal: Journal of Hepatology (2012)
Genome-Wide Scan for Japanese Familial Intracranial Aneurysms
Authors: Shigeki Yamada, Maki Utsunomiya, Kayoko Inoue, Kazuhiko Nozaki, Sumiko Inoue, Katsunobu Takenaka, Nobuo Hashimoto, Akio Koizumi
Journal: Circulation (2004)

Genetic factors have an important role in the pathogenesis of intracranial aneurysm (IA). The results of previous studies have suggested several loci.From 29 IA families with > or =3 individuals affected by IA, we used nonparametric (model-free) methods for linkage analyses, using GENEHUNTER and Merlin software. Genome-wide linkage analyses revealed 3 regions on chromosomes 17cen (maximum nonparametric logarithm of the odds score [MNS] = 3.00, nominal P=0.001), 19q13 (MNS=2.15, nominal P=0.020), and Xp22 (MNS=2.16, nominal P=0.019). We tested 4 candidate genes in these regions: the microfibril-associated protein 4 gene (MFAP4) and the promoter polymorphism of the inducible nitric oxide synthase gene (NOS2A) on chromosome 17cen, the epsilon genotypes of the apolipoprotein E gene (APOE) on chromosome 19q13, and the angiotensin I converting enzyme 2 gene (ACE2) on chromosome Xp22. Associations of their polymorphisms with IA were evaluated by a case-control study (100 cases: 29 probands from IA families and 71 unrelated subjects with IAs, 100 unrelated control subjects [unaffected members with IAs and absence of family history of IAs]). However, the case-control study showed that none of the polymorphisms of the examined genes had associations with IA.A genome-wide scan in 29 Japanese families with a high degree of familial clustering revealed 1 suggestive linkage region on chromosome 17cen and 2 potentially interesting regions on chromosomes 19q13 and Xp22. These regions were consistent with previous findings in various populations.
The IL1-like cytokine IL33 and its receptor ST2 are abnormally expressed in the affected skin and visceral organs of patients with systemic sclerosis
Authors: Mirko Manetti, Lidia Ibba-Manneschi, Vasiliki Liakouli, Serena Guiducci, Anna Franca Milia, Gemma Benelli, Alessandra Marrelli, Maria Letizia Conforti, Eloisa Romano, Roberto Giacomelli, Marco Matucci-Cerinic, Paola Cipriani
Journal: Annals of the Rheumatic Diseases (2009)

Background Early endothelial cell (EC) activation/damage and profibrotic Th2-associated cytokines play a pivotal role in systemic sclerosis (SSc). Interleukin 33 (IL33) is a novel member of the IL1 family that promotes Th2 responses and inflammation through the ST2 receptor. IL33 is also a chromatin-associated transcriptional regulator in ECs. Objective To investigate the role of the IL33/ST2 axis in SSc. Methods Skin biopsies were obtained from 30 patients with SSc (15 early/15 late stage) and 10 healthy subjects. Lung, kidney, heart, oesophagus, stomach, placenta biopsies and bronchoalveolar lavage cells from patients with SSc and controls were also analysed. IL33/ST2 expression was investigated by immunohistology, confocal immunofluorescence microscopy, western blotting and RT-PCR. Results In skin biopsies from control subjects, constitutive nuclear IL33 protein expression was found in dermal ECs and keratinocytes, while ST2 was weakly expressed in ECs and fibroblasts. In skin biopsies from patients with early SSc, IL33 protein was downregulated or absent in ECs and epidermis while IL33 mRNA was normally expressed or even upregulated. Moreover, ECs, perivascular infiltrating mast cells, CD68-positive macrophages, CD3-positive T cells, CD20-positive B cells and activated fibroblasts/myofibroblasts exhibited strong ST2 expression. In skin biopsies from patients with late SSc, IL33 was constitutively found in most ECs while ST2 immunostaining was weaker. In early SSc, the loss of endothelial IL33 protein and the overexpression of ST2 involved all affected organs. Dermal and pulmonary fibroblasts showed IL33 expression in SSc. Conclusion IL33 and ST2 are abnormally expressed in SSc. In early SSc, upon EC activation/damage IL33 may be mobilised from ECs to signal through ST2 in key profibrotic players such as inflammatory/immune cells and fibroblasts/myofibroblasts.
A comparison of treatment with dithranol and calcipotriol on the clinical severity and quality of life in patients with psoriasis
Authors: None Wall, None Poyner, None Menday
Journal: British Journal of Dermatology (1998)

In a multicentre, randomized, open study, 306 patients of either sex, over 18 years of age with stable chronic plaque psoriasis > 100 cm2 in surface area, and who gave informed consent, applied Dovonex (calcipotriol) ointment (50 μg/g) twice daily or Dithrocream (short‐contact dithranol) 0.1–2% for up to 3 months. The number of patients 'cleared' or with 'marked improvement' at the end of treatment were: investigators' assessment—calcipotriol 92 of 153 (60.1%); dithranol 67 of 131 (51.1%); odds ratio 1.44 [95% confidence interval (CI) 0.90, 2.31; P = 0.128]; patients' assessment—calcipotriol 93 of 153 (60.8%); dithranol 65 of 131 (49.6%); odds ratio 1.57 (95% CI 0.98, 2.52; P = 0.059). Significant improvement in patients' quality of life as assessed by the Psoriasis Disability Index (PDI) and the Sickness Impact Profile (SIP) were seen in both treatment groups. Reduction in the total mean score for PDI was 6.5 in the calcipotriol group (95% CI 4.4, 8.6; P = 0.001) and 3.7 in the dithranol group (95% CI 1.1, 6.3; P = 0.005). The reduction in the total mean score for SIP was 2.8 in the calcipotriol group (95% CI 1.4, 4.3; P < 0.001) and 1.7 in the dithranol group (95% CI 0.2, 3.1; P = 0.024). Calcipotriol treatment tended to have advantages over treatment with dithranol in improving quality of life.
Dehydroepiandrosterone Administration Counteracts Oxidative Imbalance and Advanced Glycation End Product Formation in Type 2 Diabetic Patients
Authors: Enrico Brignardello, Cristina Runzo, Manuela Aragno, Maria Graziella Catalano, Maurizio Cassader, Paolo Cavallo Perin, Giuseppe Boccuzzi
Journal: Diabetes Care (2007)

OBJECTIVE—Dehydroepiandrosterone (DHEA) has been shown to prevent oxidative stress in several in vivo and in vitro models. This study aimed to evaluate the effects of DHEA administration on oxidative stress, pentosidine concentration, and tumor necrosis factor (TNF)-α/TNF-α receptor system activity in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—Twenty patients were enrolled in the study and randomly assigned to the DHEA (n = 10) or placebo (n = 10) group. Twenty healthy sex- and age-matched subjects with normal glucose levels served as control subjects. DHEA was given as a single daily dose of 50 mg for 12 weeks. RESULTS—Oxidative stress parameters were significantly higher in diabetic patients versus control subjects. Pentosidine levels, as well as soluble TNF receptor (sTNF-R)I and sTNF-RII, were also higher in diabetic patients. After DHEA, plasma levels of reactive oxygen species and hydroxynonenal dropped by 53 and 47%, respectively, whereas the nonenzymatic antioxidants glutathione and vitamin E increased (+38 and +76%, respectively). The same changes in oxidative parameters were detected in peripheral blood mononuclear cells (PBMCs). DHEA treatment also induced a marked decrease of pentosidine plasma concentration in diabetic patients (−50%). Moreover, the TNF-α/TNF-α receptor system was shown to be less activated after DHEA treatment, in both plasma and PBMCs. CONCLUSIONS—Data indicate that DHEA treatment ameliorates the oxidative imbalance induced by hyperglycemia, downregulates the TNF-α/TNF-α receptor system, and prevents advanced glycation end product formation, suggesting a beneficial effect on the onset and/or progression of chronic complications in type 2 diabetic patients.
Renal-Retinal Ciliopathy Gene Sdccag8 Regulates DNA Damage Response Signaling
Authors: Rannar Airik, Gisela G. Slaats, Zhi Guo, Anna-Carina Weiss, Naheed Khan, Amiya Ghosh, Toby W. Hurd, Simon Bekker-Jensen, Jacob M. Schrøder, Steve J. Elledge, Jens S. Andersen, Andreas Kispert, Maddalena Castelli, Alessandra Boletta, Rachel H. Giles, Friedhelm Hildebrandt
Journal: Journal of the American Society of Nephrology (2014)

Nephronophthisis-related ciliopathies (NPHP-RCs) are developmental and degenerative kidney diseases that are frequently associated with extrarenal pathologies such as retinal degeneration, obesity, and intellectual disability. We recently identified mutations in a gene encoding the centrosomal protein SDCCAG8 as causing NPHP type 10 in humans. To study the role of Sdccag8 in disease pathogenesis, we generated a Sdccag8 gene-trap mouse line. Homozygous Sdccag8(gt/gt) mice lacked the wild-type Sdccag8 transcript and protein, and recapitulated the human phenotypes of NPHP and retinal degeneration. These mice exhibited early onset retinal degeneration that was associated with rhodopsin mislocalization in the photoreceptors and reduced cone cell numbers, and led to progressive loss of vision. By contrast, renal histologic changes occurred later, and no global ciliary defects were observed in the kidneys. Instead, renal pathology was associated with elevated levels of DNA damage response signaling activity. Cell culture studies confirmed the aberrant activation of DNA damage response in Sdccag8(gt/gt)-derived cells, characterized by elevated levels of γH2AX and phosphorylated ATM and cell cycle profile abnormalities. Our analysis of Sdccag8(gt/gt) mice indicates that the pleiotropic phenotypes in these mice may arise through multiple tissue-specific disease mechanisms.