tbuckley/cabot-search huggingface dataset:
SAT0007 Systemic Lupus Erythematosus: Survival Analysis in Patients Followed at A Tertiary Care Center in Southern Brazil
Authors: A.A. Gasparin, J. Hendler, L. Souza, R. Chakr, A.L. Moro, V. Hax, D. Zanchet, I. Siqueira, P.E. Palominos, C. Brenol, C. Kohem, R. Xavier, J.C. Brenol, O.A. Monticielo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic lupus erythematosus (SLE) patients have shorter survival when compared with general population.<sup>1</sup> Previous studies have reported that disease activity, complications associated with treatment and cardiovascular events are primarily responsible for mortality in these patients.<sup>2</sup> <h3>Objectives</h3> The present study aims at analyzing the 5-year survival rate of SLE patients and at identifying potential factors associated with mortality. <h3>Methods</h3> This cohort study consisted of 151 SLE patients attending the Rheumatology Clinic of Hospital de Clínicas de Porto Alegre. Patients who started follow-up between 2004 and 2008 were selected. Data were obtained from medical chart review, standardized forms fulfilled in every visit and telephone contact with patients with no visits in the previous 6 months. <h3>Results</h3> The study population was composed predominantly by females (92.7%) and caucasians (66.9%). The mean (±SD) age at diagnosis was 34.3±15.4 years. The total number of deaths was 14 (9.27%). The 5-year survival rate was 95.2%. For subjects that died the median (IQR) survival was 5.0 years (4.0-7.5) after starting follow-up. The main causes of death were infection (57.1%) and disease activity (35.7%). Bacterial infections were the most common type (35.6%). The most common site of infection was the respiratory tract (28.5%). The leading causes of death by SLE activity were hematologic (21.0%) and neurological (14.3%). No statistically significant difference was found between deaths and non-deaths in relation to age at diagnosis, disease classification criteria, presence of autoantibodies, Sjögren9s syndrome, antiphospholipid syndrome or other autoimmune disease. The disease activity index measured by SLEDAI was similar between groups. The chronicity index measured by SLICC was higher in the group of deaths (2 vs. zero) (p&lt;0.001). Cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity and smoking) were not associated with mortality. Similarly, the use of immunosuppressive doses of steroids, hydroxychloroquine, cyclophosphamide, mycophenolate mofetil, azathioprine and rituximab did not have association with mortality. <h3>Conclusions</h3> Five-year survival rate was over 90% as demonstrated by other authors. As infection was the main cause of death, preventive measures such as vaccination should be considered. SLICC was higher in patients who died, but other features, including cardiovascular factors were not different, probably due to the small number of events. <h3>References</h3> Arthritis &amp; Rheumatism. 2006;54(8): 2550–2557. Arthritis Care Res (Hoboken). 2013 Sep 19. doi: 10.1002/acr.22173. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4165
Smoking and COPD: what really are the risks?
Authors: S. Marsh, S. Aldington, P. Shirtcliffe, M. Weatherall, R. Beasley
Journal: European Respiratory Journal (2006)

Health care technology is continuously moving forward with great advances in all fields of medicine. The way in which health care is delivered has been stuck in a primary care/secondary care model, which is failing to meet patients9 needs. Existing structures are inefficient because they do not maximise use of skills. A new way of delivering services is proposed using an intermediate level specialist--a general practitioner with a special clinical interest (GPSCI), to increase access at a location close to the patient while giving support to the wider primary health community. We explore how the role of GPSCI might work using the field of respiratory medicine as an exemplar. The concept is transferable to other therapeutic areas.
CAUSES OF DEATH IN ASYMPTOMATIC AORTIC STENOSIS IN JAPAN
Authors: Satoko Wada, Takashi Murou, Hiroki Oe, Yoshiki Matsumura, Kenichi Sugioka, Ryo Ohtsuka, Yasuhiko Takemoto, Takeshi Hozumi, Minoru Yoshiyama
Journal: Journal of the American College of Cardiology (2010)
Mesenchymal precursor cells
Authors: M Corr
Journal: Annals of the Rheumatic Diseases (2002)

What are mesenchymal precursor (stem) cells doing in rheumatoid arthritis joints?

Genes implicated in limb development and bone and joint formation,1,2 particularly members of the segment polarity family that encode components of the hedgehog and wingless/Wnt signalling pathways, have recently been identified in inflamed synovial tissues,3,4 prompting speculation about their role in the pathogenesis of rheumatoid arthritis (RA) (this issue, 6). In the limb bud of the embryo these genes are associated with primitive mesenchymal cells, which can be identified by their expression of heterodimeric surface membrane molecules that bind members of the transforming growth factor β super family, including bone morphogenetic protein receptors (BMPR), endoglin, anaplastic lymphoma kinase 1, and transforming growth factor β receptors.5,6 Postnatal bone marrow has similar mesenchymal progenitor cells (MPC) that provide the reticular stroma which supports haemopoiesis, and when appropriately stimulated MPC can give rise to bone, cartilage, fat, muscle, or fibrous tissues.6,7 RA synovium also contains cells with phenotypic and functional characteristics of MPC.8,9

The primordial appendicular skeleton begins as a condensed rod of primitive MPC that develop into articular structures.1 Among isolated normal rabbit and human synovial fibroblasts there is a minority population of cells that can be induced into osteogenic, chondrogenic, and adipogenic pathways, suggesting that a few undifferentiated MPC are normally present in synovial tissues.10,11 Their numbers are greatly increased in RA synovial tissues; 5–10 times more BMPR+ cells are identified in the intimal lining,12 and specific members of the Wnt family (5a and 13) are preferentially expressed in suspensions of whole synovium.3 Such findings may reflect either an expansion of a local population of MPC or a migration of MPC from the marrow into the inflamed joint. Both scenarios assume that the disease process …
The mutation profile of JAK2 and CALR in Chinese Han patients with Philadelphia chromosome-negative myeloproliferative neoplasms
Authors: Zhiyuan Wu, Xinju Zhang, Xiao Xu, Yuming Chen, Tingting Hu, Zhihua Kang, Shibao Li, Hua Wang, Weiwei Liu, Xiaochao Ma, Ming Guan
Journal: Journal of Hematology & Oncology (2014)

Mutations in JAK2, MPL and CALR are highly relevant to the Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs). We performed high resolution melting analysis and Sanger sequencing together with T-A cloning to elucidate the unique mutation profile of these genes, in Chinese patients with MPNs. Peripheral blood DNA samples were obtained from 80 patients with polycythemia vera (PV), 80 patients with essential thrombocytosis (ET) and 50 patients with primary myelofibrosis (PMF). Ten PV patients were identified with diverse JAK2 exon 12 mutations. Five novel JAK2 Exon 12 mutation patterns (M532V/E543G, N533D, M535I/H538Y/K549I, E543G and D544N) were described. JAK2 V617F was detected in 140 samples (66 PV, 45 ET and 29 PMF). JAK2 Exon 12 mutations were prevalent (13%) and variable in the Chinese patients. Compared with PV patients with JAK2 V617F mutations, PV patients with JAK2 exon 12 mutations had an earlier median onset of disease (P = 0.0013). MPL W515L/K mutations were discerned in 4 ET and 3 PMF patients. Two kinds of CALR mutation, c. 1179_1230del and c. 1234_1235insTTGTC were detected in 20 ET and 16 PMF patients. A novel CALR mutation pattern (c. 1173_1223del/c. 1179_1230del) was identified in 2 PMF samples. In addition, 17 scattered point mutations in CALR c.1153 to c.1255 were also detected in 13 cases with CALR frame-shifting variations and 2 cases without CALR frame-shifting variations. Female patients showed a predisposition to CALR mutations (P = 0.0035). Chinese Ph-negative MPN patients have a unique mutation landscape in the common molecular markers of MPN diagnosis. Validation of the molecular diagnostic pipeline should be emphasized since there is a considerable ethnical diversity in the molecular profiles of Ph-negative MPNs.
Malignant pleural mesothelioma: A retrospective analysis of 32 cases
Authors: Nilgün Yilmaz Demirci, Ülkü Yilmaz, Abdullah Irfan Tastepe, Sükran Ülger, Çigdem Biber, Aydin Yilmaz, Yurdanur Erdogan
Journal: European Respiratory Journal (2014)

Malignant pleural mesothelioma (MPM), is a rare and aggressive tumor of the pleura arising from mesothelial cells with increasing incidence. In our study we evaluated 32 patients who were diagnosed as malignant pleural mesothelioma and were performed surgery ± chemotherapy ± radiotherapy between 2008 - 2012 retrospectively. Clinical characteristics, treatment responses were recorded.Ther were 15 women and 17 men with a mean age of 54. Histopathologically, 19 (59.3%) cases were epithelial type, 13 (40.6%) cases were mixed type. Extrapleural pneumonectomy (EPP) + chemotherapy + radiotherapy were performed to eight patients, pleurectomy / decortication to 2 patients and 22 patients underwent palliative radiotherapy and chemotherapy. While the average life expectancy of all patients was 14.4 months, in the EPP group 22.3 months and in palliative chemotherapy ± radiotherapy group was 11.8 months. None of the patients who underwent EPP perioperative mortality was observed. Although the number of cases of our study is small, this study shows that in very well selected patients with early-stage epithelial MPM survival advantage could be obtained with multimodality treatment and our results show it is consistent with the literature.
Molecular mechanisms and biological plausibility underlying the malignant transformation of endometriosis: a critical analysis
Authors: Paola Viganó, Edgardo Somigliana, Ilda Chiodo, Annalisa Abbiati, Paolo Vercellini
Journal: Human Reproduction Update (2005)

Although population-based studies have unequivocally reported an increased risk of ovarian cancer in women with endometriosis, the biological evidence supporting the idea of endometriosis as a preneoplastic condition is scanty and not well substantiated. The fundamental features of human neoplasms (monoclonal growth, genetic changes, mutations in tumour suppressor genes and replicative advantage) have been evaluated in endometriotic lesions but results obtained are discordant. It is plausible that ectopic glands may expand monoclonally but the entity of this phenomenon is debated. According to some allelotyping studies, from one-third to one-half of endometriosis lesions would harbour somatic genetic changes in chromosomal regions supposed to contain genes involved in ovarian tumourigenesis, especially for the endometrioid histotype. These findings would be consistent with the progression model for carcinogenesis from the benign precursor to ovarian cancer but they could not be unequivocally replicated. Gene mutational studies are rare in this context. A single group has found missense mutations and deletions of PTEN gene in about 20% of ovarian endometriotic cysts. Moreover, in a model of genetically engineered mice harbouring an oncogenic allele of K-ras resulting in benign lesions reminiscent of endometriosis, a conditional deletion of PTEN caused the progression towards the endometrioid tumour. Based on these data, the causal link between endometriosis and ovarian endometrioid/clear cell carcinomas remains to be defined both in terms of entity of association and of undelying molecular mechanisms.
Ultrasonographic assessment of osteophytes in 127 patients with hand osteoarthritis: exploring reliability and associations with MRI, radiographs and clinical joint findings
Authors: Alexander Mathiessen, Ida Kristin Haugen, Barbara Slatkowsky-Christensen, Pernille Bøyesen, Tore K Kvien, Hilde Berner Hammer
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To investigate the reliability of ultrasonographic assessment of osteophytes and explore the concordance of osteophytes detected by ultrasound, MRI, conventional radiography (CR) and clinical joint examination in patients with hand osteoarthritis (HOA). <h3>Methods</h3> The study included 127 HOA patients (116 women, mean age 68.6 years (SD 5.8)) with ultrasound, CR and clinical examination of both hands and MRI of dominant hand. Osteophytes were assessed by all imaging modalities on 0–3 scales, whereas clinical bony enlargement was assessed as absent/present. An ultrasound atlas of ostephytes was developed, and the intra and inter-reader reliability of scoring ultrasound osteophytes on still images using the atlas as reference was examined. The reliability for ultrasound readings was examined with κ and percentage exact agreement (PEA) and percentage close agreement (PCA), and the sensitivity, specificity and PEA/PCA of ultrasound was calculated in comparison with MRI, CR and clinical examination. <h3>Results</h3> Ultrasound had high sensitivity (0.83) and specificity (0.75) in detecting osteophytes compared with MRI, with excellent PCA (96.1%). Moderate/large osteophytes (grade 2–3) were demonstrated more often by ultrasound (n=401) than by MRI (n=288) in 851 interphalangeal joints. Ultrasound detected more osteophytes (53.2%) than CR (30.0%) and clinical examination (36.9%). Intra and inter-reader reliability of ultrasound was excellent (PEA &gt;88%, PCA 100% and weighted kappa &gt;0.91). <h3>Conclusion</h3> Ultrasound can reliably assess osteophytes in patients with HOA. Good agreement was found between osteophytes detected by ultrasound and MRI, while ultrasound was more sensitive than CR and clinical examination, which could be due to a multiplanar joint demonstration by ultrasound.
Detection of early-stage lung disease in cystic fibrosis; comparing the sensitivity of 3He and 1H MRI, CT and LCI
Authors: Helen Marshall, David Hughes, Alex Horsley, Felix Horn, Laurie Smith, Juan Parra-Robles, Steve Cunningham, Leanne Armstrong, Ina Aldag, Chris Taylor, Jim Wild
Journal: European Respiratory Journal (2014)

Introduction  Detection of early-stage lung disease in cystic fibrosis (CF) is critical to guide clinical treatment to prolong the onset of irreversible lung disease.   Objective  To investigate the relative sensitivity of imaging;  3 He and  1 H MRI, CT and lung clearance index (LCI) for detection of early stage lung disease in children with mild CF.   Methods  11 CF patients (7-16yrs) and 5 controls (7-14yrs) were assessed with  3 He and  1 H MRI, sitting and supine multi-breath washout (MBW), low-dose CT (patients only) and pulmonary function tests. All participants had spirometry within normal range. Quantitative  3 He MRI measures were calculated. Images were read by a paediatric chest radiologist.   Results  The  3 He MRI measures of un-ventilated volume percentage (UVP) and ventilation heterogeneity (coefficient of variation standard deviation (CV)) were significantly higher in patients than controls (UVP 4.3 vs 2.1 and CV 10.9 vs 9.8, p  Abnormalities were detected in the  3 He MRI of 10 patients, the CT of 9 patients and the  1 H MRI of 4 patients (fig 1). Sitting LCI was abnormal (>7.4) in 5 patients. All controls had normal MRI and LCI.   Conclusion  3 He MRI is more sensitive to early ventilation changes in CF than LCI,  1 H MRI or pulmonary function tests.  3 He MRI and CT detected lung abnormalities in CF children with sub-clinical disease.
A method to induce stable atopic dermatitis-like symptoms in NC/Nga mice housed with skin-lesioned mice
Authors: N. Takano, I. Arai, M. Kurachi
Journal: British Journal of Dermatology (2006)

Itching is a characteristic symptom in various forms of dermatosis, especially atopic dermatitis; consequently it is a major diagnostic criterion. All features are similar to events seen in patients, hence NC/Nga mice are considered to be a suitable model of human atopic dermatitis. However, there were data spreads in commencing time and the degree of skin lesions in NC/Nga mice.In the present study, we attempted to improve experimental conditions to induce stable skin lesions and to establish a more appropriate method. Methods NC/Nga mice were kept together with skin-lesioned mice during the experiment period (mixed-NC mice). The dermatitis scores of face, ears and rostral back were assessed. Scratching behaviour was measured using an apparatus, MicroAct (Neuroscience, Tokyo, Japan). Transepidermal water loss (TEWL) and serum total IgE levels were also measured. To observe the presence of mites, the skin of the rostral backs of the mixed-NC mice was stripped using cellulose tape. We also investigated the effects of fipronil (Wako, Osaka, Japan), an acaricidal compound, on skin lesions and scratching behaviour of these mixed-NC mice.In mixed-NC mice, skin lesions appeared from 2 weeks, worsened gradually and reached peak levels of a dermatitis score in 8 weeks. Scratching behaviour increased significantly from day 3. TEWL also increased from day 3, but total IgE increased from day 7. Mites were observed on the rostral backs of mixed-NC mice from day 3, and all mice had these mites on day 28. Giving pretreatment with fipronil (Wako), the skin lesions and scratching behaviour of mixed-NC mice was significantly suppressed.The findings of the present study suggest that the method of being kept together with skin-lesioned mice can induce stable skin lesions and scratching behaviour at an early stage, without skin lesions. This method could help investigate a more stable evaluation of the effects on symptoms of atopic dermatitis, and mechanisms of the itching. It was considered that parasitism of mites, not allergic reactions, was the pathogenesis of skin lesions and scratching behaviour in mixed-NC mice.
STUDIES ON INTRAVENOUS WATER DIURESIS AND NICOTINE AND PITRESSIN ANTIDURESIS IN NORMAL SUBJECTS AND PATIENTS WITH LIVER DISEASE 1
Authors: Stanley H. Bernstein, Raymond E. Weston, George Ross, Jacob Grossman, Irwin B. Hanenson, Louis Leiter
Journal: Journal of Clinical Investigation (1953)

The fluid retention of patients with liver disease, leading to edema and ascites, has generally been attributed to primary sodium retention with sec- ondary, obligatory water retention.However, because of the impaired water diuresis following oral hydration and the increased amounts of urinary antidiuretic activity observed in such patients, several investigators (1-4) have postulated some primary change in mechanisms influencing the release, physiological effect or inactivation of the -neurohypophyseal antidiuretic hormone.White, Rubin and Leiter (5) observed that, on the average, the maximal urine flows and periods of time required to achieve peak diuresis, during infusions of 10 ml. of intravenous glucose in water per minute, were the same in patients with liver disease and subjects with normal liver func- tion.Furthermore, intravenous administration of 0.57 mU of Pitressin per Kg., during such wa- ter diuresis, produced antidiuresis of equivalent -degree and duration in both groups.They con- cluded that there was no change in the rate of inactivation of either endogenous antidiuretic hormone or this dose of exogenous antidiuretic substance in patients with liver disease.More re- cently, Nelson and Welt (6) have confirmed these observations on essentially similar doses of Pitres- sin, i.e., 2.5-100 mU intravenously.However, they found that when much larger doses of Pitres- sin were given subcutaneously to cirrhotic patients, there was delayed recovery from antidiure- sis.They suggested that slower absorption of the large dose was the cause of the more prolonged antidiuresis.
Hepatocyte Growth Factor Induces MAPK-Dependent Formin IV Translocation in Renal Epithelial Cells
Authors: DAWN A. O'ROURKE, ZHEN-XIANG LIU, LORENZ SELLIN, KATHERINE SPOKES, ROLF ZELLER, LLOYD G. CANTLEY
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Renal epithelial tubule formation in cultured cells occurs after the addition of tubulogenic growth factors such as the hepatocyte growth factor (HGF). HGF activates the tyrosine kinase receptor c-met, initiating a series of complex events that regulate cell morphology, cell—cell interactions, and cell—matrix interactions and eventually result in the formation of branching tubular structures. The discovery that disruption of the formin gene locus in mice causes agenesis of the kidneys secondary to failure of ureteric bud outgrowth and branching tubule formation suggested that this family of proteins may be critical to the development of renal epithelial tubules. In this study, we investigated whether formin is involved in the HGF/c-met signaling pathway of in vitro tubulogenesis in renal epithelial cells. mIMCD-3 cells were analyzed by reverse transcription-PCR and found to express formin IV mRNA. With the use of an antibody that recognizes the carboxy terminus of all known formin isoforms, it was observed a formin isoform of approximately 165 kD markedly increased in the detergent soluble cell lysate after 10 min of stimulation with HGF. An antibody that is specific for formin IV was then generated and confirmed that the formin isoform regulated by HGF was formin IV. Cell fractionation and confocal localization of formin IV revealed that formin IV is primarily found in a submembranous band that co-localizes with the actin cytoskeleton and in a perinuclear location in quiescent epithelial cells but undergoes a rapid relocalization after HGF stimulation with translocation into the cell cytosol and into the nucleus. Formin IV was found to be a phosphorylation substrate for activated extracellular signal-regulated kinase in vitro, and pretreatment of cells with the mitogen-activated protein kinase inhibitor U0126 prevented the translocation of formin IV and inhibited HGF-dependent phosphorylation of formin IV in intact cells. In conclusion, activation of the c-met receptor results in cellular relocalization of formin IV in a mitogen-activated protein kinase—dependent manner.
Mucosal Biofilm Formation on Middle-Ear Mucosa in the Chinchilla Model of Otitis Media
Authors: Garth D. Ehrlich
Journal: JAMA (2002)

ContextChronic otitis media with effusion (OME) has long been considered to be a sterile inflammatory process. The previous application of molecular diagnostic technologies to OME suggests that viable bacteria are present in complex communities known as mucosal biofilms; however, direct imaging evidence of mucosal biofilms associated with OM is lacking.ObjectiveTo determine whether biofilm formation occurs in middle-ear mucosa in an experimental model of otitis media.Design and MaterialsA total of 48 research-grade, young adult chinchillas weighing 500 g were used for 2 series of animal experiments: one to obtain specimens for scanning electron microscopy and the other to obtain specimens for confocal laser scanning microscopy using vital dyes. In each series, 21 animals were bilaterally injected with viable Haemophilus influenzae bacteria and 1 was inoculated to account for expected mortality. Three served as negative controls. Effusions and mucosal specimens were collected from 2 infected animals that were euthanized at 3, 6, 12, and 24 hours and at days 2, 4, 5, 10, 16, and 22 after inoculation.Main Outcome MeasuresImages were analyzed for biofilm morphology, including presence of microcolony formation and for presence of bacteria on tissue surfaces.ResultsScanning electron microscopy demonstrated that biofilm formation was evident in all specimens from animals beginning 1 day after infection and was present through 21 days. Confocal laser scanning microscopy indicated that bacteria within the biofilms are viable.ConclusionThese preliminary findings provide evidence that mucosal biofilms form in an experimental model of otitis media and suggest that biofilm formation may be an important factor in the pathogenesis of chronic otitis media with effusion.