tbuckley/cabot-search huggingface dataset:
Progression of hand osteoarthritis over 2 years: a clinical and radiological follow-up study
Authors: S Botha-Scheepers, N Riyazi, I Watt, F R Rosendaal, E Slagboom, N Bellamy, F C Breedveld, M Kloppenburg
Journal: Annals of the Rheumatic Diseases (2008)

To investigate the course of hand osteoarthritis over 2 years by currently available outcome measures.189 participants of the Genetics, Arthrosis and Progression (GARP) study with hand osteoarthritis were followed for 2 years. Self-reported hand pain and functional limitations were assessed with the Australian/Canadian osteoarthritis hand index (AUSCAN LK 3.0). Pain intensity upon lateral pressure in the interphalangeal and thumb base joints was graded on a four-point scale. Osteophytes (0-3) and joint space narrowing (JSN) (0-3) was scored at baseline and after 2 years in interphalangeal and thumb base joints. Standardised response means (SRM) were calculated.172 (91%) patients completed the 2-year follow-up (mean age 60.5 years, 78.5% women). Statistically significant increases in self-reported pain and function scores, in pain intensity scores as well as in osteophyte and JSN total scores were seen over 2 years. SRM were 0.25, 0.23, 0.67, 0.34 and 0.35, respectively, for self-reported pain and function scores, pain intensity scores, osteophyte and JSN total scores. Radiological progression was not associated with changes in self-reported pain and function. Women in an early post-menopausal stage were especially at risk of progressing radiologically.Currently available outcome measures were able to assess progression over the relatively short time period of 2 years. Radiographic outcomes were more responsive than self-reported outcomes. Pain intensity upon lateral pressure seems to be a responsive measure but needs validation.
Assessment of the clinical usefulness of nebulised ipratropium bromide in patients with chronic airflow limitation.
Authors: I G Brown, C S Chan, C A Kelly, A G Dent, P V Zimmerman
Journal: Thorax (1984)

The effect of adding nebulised ipratropium bromide to bronchodilator treatment was studied in 20 patients with severe chronic airflow limitation. Maintenance theophylline with or without a steroid preparation was continued and comparison made between placebo, nebulised salbutamol, and a combination of nebulised salbutamol and ipratropium. Although the mean FEV1 values showed the combination to produce a small but significant increase in peak bronchodilatation over the effect of salbutamol alone, there were eight patients in whom no clinically useful improvement occurred. The remaining 12 patients did obtain clinically useful improvement in the magnitude or the duration of bronchodilatation (or both) as a result of the added ipratropium. The conclusion is that individual patients with chronic airflow limitation responded to the addition of nebulised ipratropium bromide in a variable way. Patients who could obtain additional benefit from ipratropium need to be identified by an appropriate reversibility study before its inclusion in their bronchodilator treatment.
Epidemiology and clinical characteristics of bullous congenital ichthyosiform erythroderma (keratinolytic ichthyosis) in Japan: Results from a nationwide survey
Authors: Michiko Kurosawa, Atsushi Takagi, Akiko Tamakoshi, Takashi Kawamura, Yutaka Inaba, Kazuhito Yokoyama, Yasuo Kitajima, Yumi Aoyama, Keiji Iwatsuki, Shigaku Ikeda
Journal: Journal of the American Academy of Dermatology (2012)
Adenine Phosphoribosyltransferase Deficiency as a Rare Cause of Renal Allograft Dysfunction
Authors: Kati Kaartinen, Ulla Hemmilä, Kaija Salmela, Anne Räisänen-Sokolowski, Timo Kouri, Satu Mäkelä
Journal: Journal of the American Society of Nephrology (2014)

Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder manifesting as urolithiasis or crystalline nephropathy. It leads to the generation of large amounts of poorly soluble 2,8-dihydroxyadenine excreted in urine, yielding kidney injury and in some patients, kidney failure. Early recognition of the disease, institution of xanthine analog therapy to block the formation of 2,8-dihydroxyadenine, high fluid intake, and low purine diet prevent CKD. Because of symptom variability and lack of awareness, however, the diagnosis is sometimes extremely deferred. We describe a patient with adenine phosphoribosyltransferase deficiency who was diagnosed during evaluation of a poorly functioning second kidney allograft. This report highlights the risk of renal allograft loss in patients with undiagnosed adenine phosphoribosyltransferase deficiency and the need for improved early detection of this disease.
Disseminated cutaneous Pseudallescheria boydii
Authors: E.F. BERNSTEIN, M.G. SCHUSTER, D.D. STIERITZ, P.C HEUMAN, J. UITTO
Journal: British Journal of Dermatology (1995)

As increasingly aggressive chemotherapeutic regimens are used to treat malignancy, more patients will become susceptible to various opportunistic pathogens. Specifically, several fungal organisms previously viewed as relatively non-pathogenic are more frequently causing serious disease in these patients. Identification of these organisms is of paramount importance, as some are relatively resistant to standard antifungal therapies. We report a patient with disseminated cutaneous Pseudallescheria boydii, diagnosed from histopathological examination and culture of a skin biopsy specimen. Identification of the organism was achieved shortly before the patient died. Clinicians must be aware of the numerous emerging opportunistic pathogens, which may require special culture techniques for diagnosis and varied or combined modes of therapy.
Impact of Specific Epidermal Growth Factor Receptor (<i>EGFR</i>) Mutations and Clinical Characteristics on Outcomes After Treatment With EGFR Tyrosine Kinase Inhibitors Versus Chemotherapy in <i>EGFR</i>-Mutant Lung Cancer: A Meta-Analysis
Authors: Chee Khoon Lee, Yi-Long Wu, Pei Ni Ding, Sarah J. Lord, Akira Inoue, Caicun Zhou, Tetsuya Mitsudomi, Rafael Rosell, Nick Pavlakis, Matthew Links, Val Gebski, Richard J. Gralla, James Chih-Hsin Yang
Journal: Journal of Clinical Oncology (2015)

We examined the impact of different epidermal growth factor receptor (EGFR) mutations and clinical characteristics on progression-free survival (PFS) in patients with advanced EGFR-mutated non-small-cell lung cancer treated with EGFR tyrosine kinase inhibitors (TKIs) as first-line therapy.This meta-analysis included randomized trials comparing EGFR TKIs with chemotherapy. We calculated hazard ratios (HRs) and 95% CIs for PFS for the trial population and prespecified subgroups and calculated pooled estimates of treatment efficacy using the fixed-effects inverse-variance-weighted method. All statistical tests were two sided.In seven eligible trials (1,649 patients), EGFR TKIs, compared with chemotherapy, significantly prolonged PFS overall (HR, 0.37; 95% CI, 0.32 to 0.42) and in all subgroups. For tumors with exon 19 deletions, the benefit was 50% greater (HR, 0.24; 95% CI, 0.20 to 0.29) than for tumors with exon 21 L858R substitution (HR, 0.48; 95% CI, 0.39 to 0.58; Pinteraction < .001). Never-smokers had a 36% greater benefit (HR, 0.32; 95% CI, 0.27 to 0.37) than current or former smokers (HR, 0.50; 95% CI, 0.40 to 0.63; Pinteraction < .001). Women had a 27% greater benefit (HR, 0.33; 95% CI, 0.28 to 0.38) than men (HR, 0.45; 95% CI, 0.36 to 0.55; treatment-sex interaction P = .02). Performance status, age, ethnicity, and tumor histology did not significantly predict additional benefit from EGFR TKIs.Although EGFR TKIs significantly prolonged PFS overall and in all subgroups, compared with chemotherapy, greater benefits were observed in those with exon 19 deletions, never-smokers, and women. These findings should enhance drug development and economic analyses, as well as the design and interpretation of clinical trials.
Gene Expression Profiling in Uveal Melanoma Reveals Two Molecular Classes and Predicts Metastatic Death
Authors: Michael D. Onken, Lori A. Worley, Justis P. Ehlers, J. William Harbour
Journal: Cancer Research (2004)

Abstract Melanomas are notoriously difficult to classify because of a lack of discrete clinical and pathological stages. Here, we show that primary uveal melanomas surprisingly cluster into two distinct molecular classes based on gene expression profile. Genes that discriminate class 1 (low-grade) from class 2 (high-grade) include highly significant clusters of down-regulated genes on chromosome 3 and up-regulated genes on chromosome 8q, which is consistent with previous cytogenetic studies. A three-gene signature allows biopsy-size tumor samples to be assigned accurately to tumor classes using either array or PCR platforms. Most importantly, this molecular classification strongly predicts metastatic death and outperforms other clinical and pathological prognostic indicators. These studies offer new insights into melanoma pathogenesis, and they provide a practical foundation for effective clinical predictive testing.
Immunolocalization of the Four Prostaglandin E2 Receptor Proteins EP1, EP2, EP3, and EP4 in Human Kidney
Authors: RUTA MORATH, THOMAS KLEIN, HANNSJÖRG W. SEYBERTH, ROLF M. NÜSING
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Four prostaglandin E 2 receptor subtypes designated EP1, EP2, EP3, and EP4 have been shown to mediate a variety of effects of prostaglandin E 2 (PGE 2 ) on glomerular hemodynamics, tubular salt and water reabsorption, and on blood vessels in the human kidney. Despite the important role of renal PGE 2 , the localization of PGE 2 receptor proteins in the human kidney is unknown. The present study used antipeptide antibodies to the EP1 to EP4 receptor proteins for immunolocalization in human kidney tissue. Immunoblot studies using these antibodies demonstrated distinct bands in membrane fraction from human kidney. By means of immunohistochemistry, expression of the human EP1 receptor subtype protein in renal tissue was detected mainly in connecting segments, cortical and medullary collecting ducts, and in the media of arteries and afferent and efferent arterioles. The human EP2 receptor subtype protein was detectable only in the media of arteries and arterioles. The human EP3 receptor subtype protein was strongly expressed in glomeruli, Tamm-Horsfall negative late distal convoluted tubules, connecting segments, cortical and medullary collecting ducts, as well as in the media and the endothelial cells of arteries and arterioles. Staining of the human EP4 receptor subtype protein was observed in glomeruli and in the media of arteries. However, no signal of either receptor subtype was detected in the thick ascending limb, the macula densa, or in adjacent juxtaglomerular cells. These results support the concept that PGE 2 modulates specific functions in different anatomical structures of the human kidney.
The measurement of exhaled carbon monoxide is influenced by airflow obstruction
Authors: B Togores, M Bosch, AG Agusti
Journal: European Respiratory Journal (2000)

The concentration of carboxyhaemoglobin (COHb) is often estimated from measurements of carbon monoxide in the exhaled air (COexh). This study investigates whether the presence of airflow obstruction significantly alters the relationship between COexh and COHb. Eighty-one regular smokers were prospectively studied and divided in four groups according to the presence and severity of airflow obstruction (none, mild, moderate, severe). In each subject, the authors measured in this order: 1) arterial blood gases; 2) haemoglobin concentration and COHb (by co-oxymetry); 3) COexh; 4) lung volumes; and 5) forced spirometry. The size of the measurement error (deltaCO) was calculated from the difference between COHb and COexh. Neither the smoking history nor COexh were different in the four groups of subjects studied. In contrast, deltaCO increased in parallel to the degree of airflow obstruction. DeltaCO was &gt;2% (a threshold value normally used in the clinic to separate smokers from nonsmokers) only in patients with severe airflow obstruction. A stepwise multivariate analysis showed that both forced expiratory volume in one second (FEV1) (percentage reference) and COHb contributed significantly (p&lt;0.0001) to predict deltaCO. This study shows that the estimation of carboxyhaemoglobin from exhaled carbon monoxide measurements can be inaccurate in patients with severe airflow obstruction. In these patients, the direct measurement of carboxyhaemoglobin seems advisable in clinical practice.
Cellular processing of bovine factors X and Xa by cultured bovine aortic endothelial cells.
Authors: P P Nawroth, D McCarthy, W Kisiel, D Handley, D M Stern
Journal: The Journal of Experimental Medicine (1985)

Previous studies have shown that Factor X and Factor Xa bind specifically to distinct sites on the endothelial cell surface. Since the coagulant activity of a cell-bound clotting protein is dependent on its remaining on the cell surface, endocytosis and degradation studies have been carried out. Cell-bound Factor X was internalized at 0.07 fmol/min/10(6) cells, a rate slower than its dissociation from the cell surface. Endocytosed Factor X was not degraded, but was returned to the cell surface. In contrast, Factor Xa was internalized at an initial rate of 0.38 fmol/min/10(6) cells and subsequently degraded at about the same rate. The degradation of Factor Xa was prevented by chloroquine. These results suggest that Factor Xa is internalized and degraded by a lysosomal-dependent pathway. Studies with Factor X- and Xa-colloidal gold conjugates showed endocytosis proceeding at coated pit regions, and accumulation of Factor Xa-gold particles in lysosome-like structures. Endocytosis was studied as a clearance pathway for cell-bound Factor Xa by activating Factor X with Factors IXa and VIII on the endothelial cell surface. Endocytosis of the Factor Xa formed was significant, as only 44% of the Factor Xa formed was released into the supernatant, whereas the remainder was internalized and degraded. Thus, endocytosis of Factor Xa bound to its specific endothelial cell sites may be an important factor in the balance of vessel wall hemostatic mechanisms.
Determinants of Viral Clearance and Persistence during Acute Hepatitis C Virus Infection
Authors: Robert Thimme, David Oldach, Kyong-Mi Chang, Carola Steiger, Stuart C. Ray, Francis V. Chisari
Journal: The Journal of Experimental Medicine (2001)

The virological and immunological features of hepatitis C virus (HCV) infection were studied weekly for 6 months after accidental needlestick exposure in five health care workers, four of whom developed acute hepatitis that progressed to chronicity while one subject cleared the virus. In all subjects, viremia was first detectable within 1–2 weeks of inoculation, 1 month or more before the appearance of virus-specific T cells. The subject who cleared the virus experienced a prolonged episode of acute hepatitis that coincided with a CD38+ IFN-γ− CD8+ T cell response to HCV and a small reduction in viremia. Subsequently, a strong CD4+ T cell response emerged and the CD8+ T cells became CD38− and started producing IFN-γ in response to HCV, coinciding with a rapid 100,000-fold decrease in viremia that occurred without a corresponding surge of disease activity. Chronic infection developed in two subjects who failed to produce a significant T cell response and in two other subjects who initially mounted strong CD4+ T cell responses that ultimately waned. In all subjects, viremia was higher at the peak of acute hepatitis than it was when the disease began, and the disease improved during the viremia. These results provide the first insight into the host–virus relationship in humans during the incubation phase of acute HCV infection, and they provide the only insight to date into the virological and immunological characteristics of clinically asymptomatic acute HCV infection, the commonest manifestation of this disease. In addition, the results suggest that the vigor and quality of the antiviral T cell response determines the outcome of acute HCV infection, that the ability of HCV to outpace the T cell response may contribute to its tendency to persist; that the onset of hepatitis coincides with the onset of the CD8+T cell response, that disease pathogenesis and viral clearance are mediated by different CD8+ T cell populations that control HCV by both cytolytic and noncytolytic mechanisms, and that there are different pathways to viral persistence in asymptomatic and symptomatic acute HCV infection.
Variants in MTNR1B influence fasting glucose levels
Authors: Inga Prokopenko, Claudia Langenberg, Jose C Florez, Richa Saxena, Nicole Soranzo, Gudmar Thorleifsson, Ruth J F Loos, Alisa K Manning, Anne U Jackson, Yurii Aulchenko, Simon C Potter, Michael R Erdos, Serena Sanna, Jouke-Jan Hottenga, Eleanor Wheeler, Marika Kaakinen, Valeriya Lyssenko, Wei-Min Chen, Kourosh Ahmadi, Jacques S Beckmann, Richard N Bergman, Murielle Bochud, Lori L Bonnycastle, Thomas A Buchanan, Antonio Cao, Alessandra Cervino, Lachlan Coin, Francis S Collins, Laura Crisponi, Eco J C de Geus, Abbas Dehghan, Panos Deloukas, Alex S F Doney, Paul Elliott, Nelson Freimer, Vesela Gateva, Christian Herder, Albert Hofman, Thomas E Hughes, Sarah Hunt, Thomas Illig, Michael Inouye, Bo Isomaa, Toby Johnson, Augustine Kong, Maria Krestyaninova, Johanna Kuusisto, Markku Laakso, Noha Lim, Ulf Lindblad, Cecilia M Lindgren, Owen T McCann, Karen L Mohlke, Andrew D Morris, Silvia Naitza, Marco Orrù, Colin N A Palmer, Anneli Pouta, Joshua Randall, Wolfgang Rathmann, Jouko Saramies, Paul Scheet, Laura J Scott, Angelo Scuteri, Stephen Sharp, Eric Sijbrands, Jan H Smit, Kijoung Song, Valgerdur Steinthorsdottir, Heather M Stringham, Tiinamaija Tuomi, Jaakko Tuomilehto, André G Uitterlinden, Benjamin F Voight, Dawn Waterworth, H-Erich Wichmann, Gonneke Willemsen, Jacqueline C M Witteman, Xin Yuan, Jing Hua Zhao, Eleftheria Zeggini, David Schlessinger, Manjinder Sandhu, Dorret I Boomsma, Manuela Uda, Tim D Spector, Brenda WJH Penninx, David Altshuler, Peter Vollenweider, Marjo Riitta Jarvelin, Edward Lakatta, Gerard Waeber, Caroline S Fox, Leena Peltonen, Leif C Groop, Vincent Mooser, L Adrienne Cupples, Unnur Thorsteinsdottir, Michael Boehnke, Inês Barroso, Cornelia Van Duijn, Josée Dupuis, Richard M Watanabe, Kari Stefansson, Mark I McCarthy, Nicholas J Wareham, James B Meigs, Gonçalo R Abecasis
Journal: Nature Genetics (2008)
Transcapillary Escape Rate of Albumin and Plasma Volume in Essential Hypertension
Authors: HANS-HENRIK PARVING, FINN GYNTELBERG
Journal: Circulation Research (1973)

The transcapillary escape rate of albumin, the fraction of intravascular mass of albumin that passes to the extravascular space per unit time, was determined from the disappearance of intravenously injected 131 I-labeled human serum albumin during the first 60 minutes after the injection in 10 normotensive and 18 hypertensive male subjects. The investigation was preceded by at least 12 hours of fasting and 30 minutes of rest in the supine position. The transcapillary escape rate of albumin was significantly increased in the hypertensive group: it averaged 7.6±1.2 (SD) %/hour compared with 5.6±1.1%/hour in the normotensive group ( P &lt;0.001). Similar results were obtained for the outflux of albumin, the mass of intravascular albumin that passes to the extravascular space per unit time, when identical intravascular albumin masses were compared ( P &lt;0.001). A highly significant correlation between the transcapillary escape rate of albumin and blood pressure was found in the hypertensive group ( P &lt;0.001). Therefore, the increased transcapillary escape rate and the outflux of albumin probably reflected an increase in arteriolar and capillary permeability to albumin. This increase was probably due to the high intra-arterial pressure, which induces constriction in some arteries and dilatation in others and thus allows the high intraluminal pressure to be transmitted distally with distention of the small vessel walls. Finally, a significant reduction in plasma volume was found in the hypertensive subjects ( P &lt;0.05).
Muckle-Wells syndrome: clinical and histological skin findings compatible with cold air urticaria in a large kindred
Authors: N. Haas, W. Kuster, T. Zuberbier, B.M. Henz
Journal: British Journal of Dermatology (2004)

Muckle-Wells syndrome is a rare familial disease with autosomal dominant inheritance, characterized by cold sensitivity and polyarthralgias since childhood, with possible later development of nerve deafness and renal amyloidosis. The nature of the skin manifestations is, however, not well characterized.To clarify the nature of cutaneous cold sensitivity in patients with Muckle-Wells syndrome by studying clinical aspects and histological features.Eighteen members of a family with Muckle-Wells syndrome and the recently identified mutation of the CIAS1 gene at locus 260 of chromosome 1q44 were available for study. Examination included a thorough history, physical examination and a battery of laboratory tests. In two brothers, standard cold contact and cold air provocation tests were performed, as were biopsies from normal and lesional skin.All affected family members reported an increased sensitivity to cold, dampness or changes in temperature, and most had arthritis and conjunctivitis. Eight had developed hearing loss, four renal involvement, and amyloid deposits were found in three of five patients in whom rectal biopsies were performed. Laboratory tests showed leucocytosis and elevated C-reactive protein, but no serum cold agglutinins and cryoglobulins. Skin eruptions, with weals of 0.2-3 cm, lasted from 5 to 24 h and were associated with local itching or pain as well as fever, malaise and chills. On cold provocation of two patients, lesions could be reproduced by cold air, but not by contact with an ice cube or cold water. On histology, there was increased vasodilatation, marked infiltration with neutrophils and monocytes/macrophages, and increased expression of beta 2 integrins in lesional vs. normal skin. Numbers of mast cells as well as expression of interleukin-3 and tumour necrosis factor-alpha were unchanged.Cold-induced skin lesions in Muckle-Wells syndrome represent typical generalized cold air/wind inflammatory reactions, as also observed in familial cold urticaria. Microscopic features are similar to those observed in other types of urticaria.