tbuckley/cabot-search huggingface dataset:
Ultrasound-detected inflammation predicts radiographic progression in hand osteoarthritis after 5 years
Authors: Alexander Mathiessen, Barbara Slatkowsky-Christensen, Tore K Kvien, Hilde Berner Hammer, Ida K Haugen
Journal: Annals of the Rheumatic Diseases (2015)

To examine whether ultrasound predicts radiographic hand osteoarthritis (OA) progression after 5 years.We included 78 participants (71 women, mean (SD) age 67.8 (5.2) years) from the Oslo Hand OA cohort with ultrasound examination (gray-scale (GS) synovitis and power Doppler (PD) signals) at baseline and conventional radiographs and clinical examination at baseline and 5-year follow-up. Radiographic progression was defined as an increase in global OA according to the Kellgren-Lawrence (KL) scale or progression of individual radiographic OA features. We examined whether baseline ultrasound features and clinical examination predicted radiographic progression using generalised estimating equations, adjusted for age, sex, body mass index and follow-up time.Radiographic progression occurred in 17.9% joints for KL, 12.1% for joint space narrowing, 11.7% for osteophytes and 4.5% for erosions. Ultrasound-detected inflammation predicted KL progression, and dose-response associations were observed for GS synovitis grade 1 (OR=2.8, 95% CI 1.8 to 4.2), grade 2 (OR=3.6, 95% CI 2.2 to 5.8) and grade 3 (OR=15.2, 95% CI 6.9 to 33.6), and for PD signal grade 1 (OR=2.9, 95% CI 1.2 to 6.8) and grades 2-3 (OR=12.0, 95% CI 3.5 to 41.0). Significant associations were also observed between ultrasound inflammation and progression of all individual radiographic features, and between clinical soft tissue swelling at baseline and radiographic progression.Ultrasound-detected GS synovitis and PD signals were significantly associated with radiographic progression after 5 years. This study supports the use of ultrasound as a tool to detect patients with hand OA who are likely to progress.
Reginald Arthur Shooter
Authors: A. R. M. Roe
Journal: BMJ (2014)

A leading figure in the story of the last days of the fight against smallpox, Professor Reggie Shooter, CBE, MA, MD, FRCP, FRCPath, has sadly passed away aged 97.

Reginald Arthur Shooter (“Reggie”) was the son of Rev A E Shooter, a Methodist minister, and Mabel Pinniger, the daughter of a successful Exeter businessman. His mother’s two younger brothers had both been studying medicine, but they had to cut short their studies to join the army in 1914. During the course of the conflict, both lost their lives, which lead Reggie’s grandfather to adopt him as one of his own. He paid for his education at Peterborough Lodge and Mill Hill, and he was no doubt influential in Reggie’s decision to read medicine.

A distinguished medical scientist, teacher, and academic, Reggie Shooter was educated at Mill Hill School, Gonville and Caius College, Cambridge, and then at St Bartholomew’s Hospital Medical School, London. Cricket was a major passion, and he played in the first team at prep and public schools and at Devon Colts. This was something he continued to do whilst studying at Cambridge.

He qualified from St Bartholomew’s Hospital Medical School (Bart’s), one week before the Blitz started in June. For the next 12 months, in the position of house surgeon, Reggie …
SERPINE1 -675 4G/5G polymorphism is associated with asthma severity and inhaled corticosteroid response
Authors: A. Dijkstra, D.S. Postma, M. Bruinenberg, C.C. van Diemen, H.M. Boezen, G.H. Koppelman, W. Timens, J.M. Vonk
Journal: European Respiratory Journal (2011)

Asthma is characterised by chronic airway inflammation and remodelling, which can be (partially) suppressed by inhaled corticosteroids (ICSs). Plasminogen activator inhibitor-1, encoded by the SERPINE1 gene, is the key inhibitor of the plasminogen activator system, which affects tissue repair and remodelling. We studied associations between a functional SERPINE1 -675 4G/5G promoter polymorphism and asthma development, severity and response to ICSs. Longitudinal cohorts of 281 asthmatics and their nonasthmatic spouses, and the general population (n=1,390) were studied. No significant associations were found with asthma development and immunoglobulin (Ig)E levels, or with forced expiratory volume in 1 s (FEV₁) in nonasthmatic controls. Asthmatic subjects carrying the SERPINE1 5G allele had higher IgE and lower lung function levels at follow-up, lower maximally attained lung function levels, and faster lung function decline compared with individuals with the 4G/4G genotype. ICS treatment showed an immediate improvement in FEV₁ in asthmatics carrying the 5G allele. However, these asthmatics still had the fastest rate of FEV₁ decline after initiating ICS treatment. Finally, the 5G allele was associated with a lower prevalence of complete asthma remission at follow-up. These findings suggest that SERPINE1 is not an asthma susceptibility gene, but rather affects the severity, progression and long-term ICS response in asthma.
The <i>CHRNA5-CHRNA3-CHRNB4</i> Nicotinic Receptor Subunit Gene Cluster Affects Risk for Nicotine Dependence in African-Americans and in European-Americans
Authors: Nancy L. Saccone, Jen C. Wang, Naomi Breslau, Eric O. Johnson, Dorothy Hatsukami, Scott F. Saccone, Richard A. Grucza, Lingwei Sun, Weimin Duan, John Budde, Robert C. Culverhouse, Louis Fox, Anthony L. Hinrichs, Joseph Henry Steinbach, Meng Wu, John P. Rice, Alison M. Goate, Laura J. Bierut
Journal: Cancer Research (2009)

Abstract Genetic association studies have shown the importance of variants in the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit gene cluster on chromosome 15q24-25.1 for the risk of nicotine dependence, smoking, and lung cancer in populations of European descent. We have carried out a detailed study of this region using dense genotyping in both European-Americans and African-Americans. We genotyped 75 known single nucleotide polymorphisms (SNPs) and one sequencing-discovered SNP in an African-American sample (N = 710) and in a European-American sample (N = 2,062). Cases were nicotine-dependent and controls were nondependent smokers. The nonsynonymous CHRNA5 SNP rs16969968 is the most significant SNP associated with nicotine dependence in the full sample of 2,772 subjects [P = 4.49 × 10−8; odds ratio (OR), 1.42; 95% confidence interval (CI), 1.25–1.61] as well as in African-Americans only (P = 0.015; OR, 2.04; 1.15–3.62) and in European-Americans only (P = 4.14 × 10−7; OR, 1.40; 1.23–1.59). Other SNPs that have been shown to affect the mRNA levels of CHRNA5 in European-Americans are associated with nicotine dependence in African-Americans but not in European-Americans. The CHRNA3 SNP rs578776, which has a low correlation with rs16969968, is associated with nicotine dependence in European-Americans but not in African-Americans. Less common SNPs (frequency ≤ 5%) are also associated with nicotine dependence. In summary, multiple variants in this gene cluster contribute to nicotine dependence risk, and some are also associated with functional effects on CHRNA5. The nonsynonymous SNP rs16969968, a known risk variant in populations of European-descent, is also significantly associated with risk in African-Americans. Additional SNPs contribute to risk in distinct ways in these two populations. [Cancer Res 2009;69(17):6848–56]
Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer
Authors: Johann S. de Bono, Howard I. Scher, R. Bruce Montgomery, Christopher Parker, M. Craig Miller, Henk Tissing, Gerald V. Doyle, Leon W.W.M. Terstappen, Kenneth J. Pienta, Derek Raghavan
Journal: Clinical Cancer Research (2008)

A method for enumerating circulating tumor cells (CTC) has received regulatory clearance. The primary objective of this prospective study was to establish the relationship between posttreatment CTC count and overall survival (OS) in castration-resistant prostate cancer (CRPC). Secondary objectives included determining the prognostic utility of CTC measurement before initiating therapy, and the relationship of CTC to prostate-specific antigen (PSA) changes and OS at these and other time points.Blood was drawn from CRPC patients with progressive disease starting a new line of chemotherapy before treatment and monthly thereafter. Patients were stratified into predetermined Favorable or Unfavorable groups (<5 and > or =5 CTC/7.5mL).Two hundred thirty-one of 276 enrolled patients (84%) were evaluable. Patients with Unfavorable pretreatment CTC (57%) had shorter OS (median OS, 11.5 versus 21.7 months; Cox hazard ratio, 3.3; P < 0.0001). Unfavorable posttreatment CTC counts also predicted shorter OS at 2 to 5, 6 to 8, 9 to 12, and 13 to 20 weeks (median OS, 6.7-9.5 versus 19.6-20.7 months; Cox hazard ratio, 3.6-6.5; P < 0.0001). CTC counts predicted OS better than PSA decrement algorithms at all time points; area under the receiver operator curve for CTC was 81% to 87% and 58% to 68% for 30% PSA reduction (P = 0.0218). Prognosis for patients with (a) Unfavorable baseline CTC who converted to Favorable CTC improved (6.8 to 21.3 months); (b) Favorable baseline CTC who converted to Unfavorable worsened (>26 to 9.3 months).CTC are the most accurate and independent predictor of OS in CRPC. These data led to Food and Drug Administration clearance of this assay for the evaluation of CRPC.
A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly)
Authors: V. Ballova, J.-U. Rüffer, H. Haverkamp, B. Pfistner, H.K. Müller-Hermelink, E. Dühmke, P. Worst, M. Wilhelmy, R. Naumann, M. Hentrich, H.T. Eich, A. Josting, M. Löffler, V. Diehl, A. Engert
Journal: Annals of Oncology (2004)
The CD14 C-159T polymorphism is not associated with asthma or asthma severity in an Australian adult population
Authors: M-A Kedda
Journal: Thorax (2005)

<b>Background:</b> CD14 functions as a multifunctional receptor for bacterial cell wall components including endotoxin and lipopolysaccharide and is likely to play a role in the polarisation of T lymphocytes into Th1 and Th2 subsets, thereby influencing the cytokine profile and subsequent IgE production in response to antigen/allergen contact in allergic phenotypes. A functional C-159T polymorphism has been described in the promoter region of the gene and has been associated with increased gene expression, atopy, and non-atopic asthma in different ethnic populations. A study was undertaken to examine the association between the C-159T polymorphism and asthma, asthma severity, and atopy in a large Australian white population. <b>Methods:</b> PCR-RFLP analysis was used to characterise the C-159T polymorphism in mild (n = 264), moderate (n = 225) and severe (n = 79) asthmatic patients and non-asthmatic controls (n = 443), including atopic (n = 688) and non-atopic (n = 323) individuals. Association analyses were performed using χ<sup>2</sup> tests. <b>Results:</b> There was no association between the polymorphism and asthma (p = 0.468) or asthma severity (p = 0.727), and only a very weak association with atopy (p = 0.084). A meta-analysis of all studies conducted to date revealed similar genotypic frequencies in white ethnic populations and confirmed that there was no overall association with atopy (p = 0.52) or asthma (p = 0.23), although there was significant between study heterogeneity (p = 0.01). <b>Conclusions:</b> This study confirms that there is no association between the CD14 C-159T polymorphism and asthma or asthma severity and a weak association between this polymorphism and atopy in an adult population.
A 62 year old diabetic with weight loss and lung lesions
Authors: IB Wilkinson, WJ Kinnear, RB Tattersall, ID Johnston
Journal: European Respiratory Journal (1997)

Case history A 62 year old retired paratrooper was referred by his general practitioner with new onset diabetes and a 13 year history of hypertension, which had recently been difficult to treat. He complained of frequent headaches, ankle swelling, thirst and urinary frequency. Previously, he had received various antihypertensive treatments, including diuretics, β-blockers, calcium channel antagonists, and angiotensin-converting enzyme (ACE) inhibitors. He was currently taking prazosin 1.5 mg and bendrofluazide 5 mg daily. He smoked 20 cigarettes·day-1, and had been diagnosed as suffering from chronic obstructive pulmonary disease, for which he took inhaled salbutamol as required. His alcohol intake was 80 g·week -1 . On examination, the only abnormal findings were a blood pressure of 190/110 mmHg, and mild pitting-oedema of both ankles. Fundoscopy showed grade I hypertensive changes, and his urine tested positive for glucose only. Initial investigations showed a normal full blood count, sodium 140 mmol·L -1 , potassium 2.6 mmol·L -1 , urea 6.2 mmol·L-1, creatinine 71 µmol·L-1. Random serum glucose was 12 mmol·L -1 , and the major fraction of glycosylated haemoglobin (HbAIC) 10.2% (normal range up to 5.9%). Chest radiography showed a small left-sided pleural effusion. A resting electrocardiogram (ECG) indicated left ventricular hypertrophy, and an echocardiograph revealed moderately good left ventricular function, with normal valves. A diagnosis of diabetes mellitus was made, and dietary treatment initiated. When this failed, gliclazide 80 mg b.d. was added. The patient's hypertension was treated with bendrofluazide 2.5 mg and enalapril 10 mg daily, and the hypokalaemia was corrected with Sando-K. On review 1 month later, blood sugars were still high, HbAIC was still 10.2%, and blood pressure 170/100 mmHg. Because of tiredness, general malaise and weakness, the patient was then prescribed twice daily insulin. After another month, the patient returned complaining of weight loss and depression. Oral candidiasis, balanitis, and generalized pigmentation were now apparent. The ankle oedema was much worse, and a proximal myopathy was noted. Hypokalaemia was still present. Tests were performed and gave the following results: Random cortisol, 2,000 mmol·L-1 (normal <800 mmol·L-1); high dose dexamethasone suppression test, no suppression; adrenocorticotrophic hormone (ACTH), 161 ng·L-1 (normal <100 ng·L-1); computed tomography (CT) of the pituitary gland, partially empty sella, no mass lesion; CT of the abdomen, a 1 cm mass in the right adrenal gland, otherwise normal.
Lasers in periodontal therapy
Authors: Euloir Passanezi, Carla Andreotti Damante, Maria L. Rubo de Rezende, Sebastião L. Aguiar Greghi
Journal: Periodontology 2000 (2014)

Abstract About 50 years ago, lasers started to be used in periodontal treatment following evidence that wounds produced in animals healed more quickly after being irradiated with low‐intensity lasers. Increased production of growth factors, stimulated mainly by red and infrared lasers, may participate in this process by influencing the behavior of various types of cells. High‐intensity lasers have been used as an alternative to nonsurgical periodontal therapy in root biomodification and to reduce dentin hypersensivity; low‐intensity lasers are frequently employed to improve tissue repair in regenerative procedures and in antimicrobial photodynamic therapy. Despite the abundance of promising data on the advantages of their use, there is still controversy regarding the real benefits of lasers and antimicrobial photodynamic therapy in periodontal and peri‐implant treatment. A huge variation in the parameters of laser application among studies makes comparisons very difficult. An overview of the current concepts and findings on lasers in periodontal therapy is presented with emphasis on data collected from Latin‐American researchers.
Asbestos and silica exposures reveal similar and divergent gene expression patterns and pathways related to fibrosis in human bronchial epithelial cells
Authors: Timothy Perkins, Paul Peeters, Arti Shukla, Ingrid Arijs, Niki Reynaert, Emiel Wouters, Brooke Mossman
Journal: European Respiratory Journal (2012)

Background  Asbestosis and silicosis, two common forms of pneumoconioses are caused by excessive exposure to airborne minerals, leading to pulmonary fibrosis. However, both diseases have distinct pathological presentations, which are likely due to the physicochemical characteristics of the two minerals. The epithelium is an initial target cell to come in contact with inhaled materials. The early molecular events that therefore take place in epithelial cells have a strong influence on the molecular and cellular responses that promote inflammation, lesion formation, and fibrosis.  Methods  Primary human bronchial epithelial cells were exposed to non-lethal doses of crocidolite asbestos and cristobalite silica for 24 hours. Affymetrix/GeneSifter® analysis utilizing pairwise-comparison, hierarchical cluster analysis, and Ingenuity pathway analysis® was used to reveal similar and unique gene expression patterns.  Results  Both minerals altered a number of genes related to inflammation, cell proliferation, apoptosis, cell-surface receptors, and transcription factors. Genes selectively altered by asbestos were related to evasion of apoptosis, MAPK signaling, and iron metabolism. Conversely, genes altered by silica were involved in TNF-signaling, TLR-signaling, and mitochondrial biogenesis. Similar and distinct pathways associated with inflammation and fibrosis were affected by both mineral exposures.  Conclusions  These studies exhibit initial changes in gene expression by asbestos and silica in target bronchial epithelial cells as early molecular events that may initiate the inflammatory and fibrotic responses leading to asbestosis and silicosis.
Detection of the Imbalance of Procoagulant Versus Anticoagulant Factors in Cirrhosis by a Simple Laboratory Method
Authors: Armando Tripodi, Massimo Primignani, Laura Lemma, Veena Chantarangkul, Alessandra Dell'Era, Francesca Iannuzzi, Alessio Aghemo, Pier Mannuccio Mannucci
Journal: Hepatology (2010)

Patients with cirrhosis possess an imbalance in procoagulant versus anticoagulant activity due to increased factor VIII and decreased protein C. This imbalance can be detected by thrombin-generation assays performed in the presence/absence of thrombomodulin (predicate assay) that are not readily available in clinical laboratories. We sought to assess this hypercoagulability with a simpler thrombin-generation assay performed in the presence/absence of Protac, a snake venom that activates protein C in a manner similar to thrombomodulin (new assay). We analyzed blood from 105 patients with cirrhosis and 105 healthy subjects (controls). Results for the predicate-assay or the new-assay were expressed as ratio (with:without thrombomodulin) or as Protac-induced coagulation inhibition (PICI%). By definition, high ratios or low PICI% translate into hypercoagulability. The median(range) PICI% was lower in patients (74% [31%-97%]) than controls (93% [72%-99%]; P &lt; 0.001), indicating that patients with cirrhosis are resistant to the action of Protac. This resistance resulted in greater plasma hypercoagulability in patients who were Child class C than those who were A or B. The hypercoagulability of Child C cirrhosis (63% [31%-92%]) was similar to that observed for patients with factor V Leiden (69% [15%-80%]; P = 0.59). The PICI% values were correlated with the levels of protein C (rho = 0.728, P &lt; 0.001) or factor VIII (rho = −0.517, P &lt; 0.001). Finally, the PICI% values were correlated with the predicate assay (rho = −0.580, P &lt; 0.001). Conclusion: The hypercoagulability of plasma from patients with cirrhosis can be detected with the new assay, which compares favorably with the other markers of hypercoagulability (i.e., high factor VIII and low protein C) and with the predicate-assay based on thrombin-generation with/without thrombomodulin. Advantages of the new assay over the predicate assay are easy performance and standardized results. Prospective trials are needed to ascertain whether it is useful to predict thrombosis in patients with cirrhosis. Hepatology 2010
Family-Planning Practices Among Women With Diabetes and Overweight and Obese Women in the 2002 National Survey for Family Growth
Authors: Anjel Vahratian, Jennifer S. Barber, Jean M. Lawrence, Catherine Kim
Journal: Diabetes Care (2009)

To examine contraceptive practices among diabetic women and obese women.We analyzed the responses of 5,955 participants aged 20-44 years in the 2002 National Survey for Family Growth. Diabetes, BMI, desire for pregnancy, history of infertility treatment, sexual activity, parity, and demographic variables (age, race/ethnicity, education, marital status, income, insurance, and smoking history) were obtained by self-report. Lack of contraception was defined as absence of hormonal-, barrier-, or sterilization-based methods. Associations among contraception, diabetes, and BMI category were assessed in multivariable logistic regression models in nonsterile, sexually active women.In unadjusted comparisons among sexually active women who were not sterilized, women with diabetes were more likely to lack contraception than women without diabetes (odds ratio [OR] 2.61 [95% CI 1.22-5.58]). Women with BMI >or=35 kg/m(2) were more likely to lack contraception than women with BMI <25 kg/m(2)(1.63 [1.16-2.28]), but associations between contraception use and lesser degrees of overweight and obesity were not significant. In multivariable models, women who were older (aged >or=30 vs. 20-29 years), were of non-Hispanic black race, were cohabitating, had a history of infertility treatment, and desired or were ambivalent about pregnancy were significantly more likely to lack contraception. The associations among diabetes, BMI, and contraception were no longer significant after these adjustments.Older women with diabetes and obesity who desire pregnancy, regardless of pregnancy intention, should be targeted for preconceptive management.
Classifying Severity of Cystic Fibrosis Lung Disease Using Longitudinal Pulmonary Function Data
Authors: Mark D. Schluchter, Michael W. Konstan, Mitchell L. Drumm, James R. Yankaskas, Michael R. Knowles
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

The study of genetic modifiers in cystic fibrosis (CF) lung disease requires rigorous phenotyping. One type of genetic association study design compares polymorphisms in patients at extremes of phenotype, requiring accurate classification of pulmonary disease at varying ages.To evaluate approaches to quantify severity of pulmonary disease and their ability to discriminate between patients with CF at the extremes of phenotype.DeltaF508 homozygotes (n = 828) were initially classified as "severe" (approximate lowest quartile of FEV(1) (% pred) for age, 8-25 yr) or "mild" disease (highest quartile of FEV(1) for age, > or = 15 yr). FEV(1) measurements from the 5 yr before enrollment (total = 18,501 measurements; average 23 per subject) were analyzed with mixed models, and patient-specific estimates of FEV(1) (% pred) at ages 5, 10, 15, 20, and 25 yr and slope of FEV(1) versus age were examined for their ability to discriminate between groups using receiver operating characteristics (ROC) curve areas.Logistic regression of severity group on mixed model (empirical Bayes) estimates of intercept and slope of FEV(1) (% pred) versus age discriminated better than did classification using FEV(1) slope alone (ROC area = 0.995 vs. 0.821) and was equivalent to using estimated FEV(1) at 20 yr of age as a single discriminator. The estimated survival percentile from a joint survival/longitudinal model provided equally good classification (ROC area = 0.994).In CF, estimated FEV(1) (% pred) at 20 yr of age and the estimated survival percentile are useful indices of pulmonary disease severity.