tbuckley/cabot-search huggingface dataset:
Long-term prognosis of autoimmune pancreatitis with and without corticosteroid treatment
Authors: K. Hirano, M. Tada, H. Isayama, H. Yagioka, T. Sasaki, H. Kogure, Y. Nakai, N. Sasahira, T. Tsujino, H. Yoshida, T. Kawabe, M. Omata
Journal: Gut (2007)

<h3>Objectives:</h3> Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis, and has a favourable response to corticosteroid treatment (CST). Little is known, however, about the long-term outcome of AIP. This study aimed to document the prognosis without and with CST, and to examine the indication for CST. <h3>Patients and methods:</h3> The prognosis and clinical features of 23 patients without CST and 19 patients treated with CST from onset were investigated. In addition, factors concerning the late occurrence of unfavourable events related to AIP were examined. <h3>Results:</h3> The patients without CST were 19 men and four women, with an average age of 66 years. After an average observation period of 25 months, 16 patients (70%) developed unfavourable events including obstructive jaundice as a result of distal bile duct stenosis in four, growing pseudocyst in one, sclerogenic changes of extrapancreatic bile duct in nine, hydronephrosis as a result of retroperitoneal fibrosis in one, and interstitial nephritis in one. Patients with obstructive jaundice at onset showed a higher cumulative event occurrence rate (p = 0.025). The patients treated with CST were 16 men and three women, with an average age of 64 years. After an average observation period of 23 months, six patients (32%) developed unfavourable events consisting of interstitial pneumonia in three, and a recurrence of obstructive jaundice in three. In multivariate analysis, CST (HR 0.33, 95% CI 0.12–0.89, p = 0.029) and obstructive jaundice at onset (HR 3.09, 95% CI 1.14–8.32, p = 0.026) were significant predictive factors for unfavourable events. <h3>Conclusion:</h3> CST could reduce AIP-related unfavourable events. The early introduction of CST is recommended especially for patients with obstructive jaundice.
Characterization of the molecular mechanisms underlying increased ischemic damage in the <i>aldehyde dehydrogenase 2</i> genetic polymorphism using a human induced pluripotent stem cell model system
Authors: Antje D. Ebert, Kazuki Kodo, Ping Liang, Haodi Wu, Bruno C. Huber, Johannes Riegler, Jared Churko, Jaecheol Lee, Patricia de Almeida, Feng Lan, Sebastian Diecke, Paul W. Burridge, Joseph D. Gold, Daria Mochly-Rosen, Joseph C. Wu
Journal: Science Translational Medicine (2014)

The decrease of function in the ALDH2*2 genotype disrupts an important cardioprotective oxidative stress regulatory circuit, thus increasing cardiac cell death after ischemic insult.
Anti-CEA immunoscintigraphy and computed tomographic scanning in the preoperative evaluation of mediastinal lymph nodes in lung cancer.
Authors: G Buccheri, A Biggi, D Ferrigno, M Quaranta, A Leone, G Vassallo, F Pugno
Journal: Thorax (1996)

<h3>Abstract</h3> Characterizing the developmental trajectories of cognitive functions such as learning, memory and decision making across the lifespan faces fundamental challenges. Cognitive functions typically encompass several processes that can be differentially affected by age. Methodological issues also arise when comparisons are made across age groups that differ in basic performance measures, such as in average response times (RTs). Here we focus on procedural learning – a fundamental cognitive function that underlies the acquisition of cognitive, social, and motor skills – and demonstrate how disentangling subprocesses of learning and controlling for differences in average RTs can reveal different developmental trajectories across the human lifespan. Two hundred-seventy participants aged between 7 and 85 years performed a probabilistic sequence learning task that enabled us to separately measure two processes of procedural learning, namely general skill learning and statistical learning. Using raw RT measures, in <i>between</i>-group comparisons, we found a U-shaped trajectory with children and older adults exhibiting greater general skill learning compared to adolescents and younger adults. However, when we controlled for differences in average RTs (either by using ratio scores or focusing on a subsample of participants with similar average speed), only children (but not older adults) demonstrated superior general skill learning consistently across analyses. Testing the relationship between average RTs and general skill learning <i>within</i> age groups shed light on further age-related differences, suggesting that general skill learning measures are more affected by average speed in some age groups. Consistent with previous studies of learning probabilistic regularities, statistical learning showed a gradual decline across the lifespan, and learning performance seemed to be independent of average speed, regardless of the age group. Overall, our results suggest that children are superior learners in various aspects of procedural learning, including both general skill and statistical learning. Our study also highlights the importance to test, and control for, the effect of average speed on other RT measures of cognitive functions, which can fundamentally affect the interpretation of group differences in developmental, aging and clinical psychology and neuroscience studies.
Upregulation of renal and systemic cyclooxygenase-2 in patients with active lupus nephritis.
Authors: S Tomasoni, M Noris, S Zappella, E Gotti, F Casiraghi, S Bonazzola, A Benigni, G Remuzzi
Journal: Journal of the American Society of Nephrology (1998)

In lupus nephritis (LN), renal thromboxane A2 (TXA2) production is increased, and inhibition of TXA2 activity improves renal function. In patients with LN, renal function depends very much on vasodilatory prostaglandins, and indeed inhibiting the prostaglandin-forming enzyme cyclooxygenase (COX) with aspirin or related compounds was detrimental on renal hemodynamics in these patients. There are no data so far on whether the excessive TXA2 production in LN derives from upregulation of type I or type II isoforms of COX. It was found that TXB2 synthesis and COX-2 gene expression were higher in peripheral blood mononuclear cells from patients with active LN compared to patients in the inactive form of the disease and to healthy subjects. Unlike COX-2, levels of COX-1 mRNA were comparable in lupus patients and control subjects and were not influenced by the disease activity. Immunoperoxidase studies on kidney biopsies showed COX-1 staining in glomerular arterioles and other renal vessels, with no evident difference between lupus biopsies and control specimens taken from either individuals who were free of renal disease or patients with non-lupus nephropathies. In contrast, COX-2 staining was definitely stronger in specimens from patients with active LN than control specimens. In active LN, COX-2-specific staining was localized mainly in the glomeruli, with a weaker signal on tubuli and in the interstitium. Double-staining studies with an antibody against the macrophage marker CD68 and an anti-COX-2 antibody definitely showed that COX-2 and CD68 often colocalized on the same cell, with only occasional glomerular COX-2-stained mesangial areas. Patients with non-lupus nephropathies had no increase in renal COX-2 expression. These results indicate that COX-2 upregulation is a specific finding of active LN and that monocytes infiltrating the glomeruli contribute to the exaggerated local synthesis of TXA2. If this is correct, COX-2 may soon become a target for therapeutic intervention in this disease.
* P21/CDKN1A germline variation and low penetrance predisposition to colorectal cancer
Authors: K. J. Monahan, S. Spain, H. J. Thomas, I. P. Tomlinson
Journal: Gut (2011)

<h3>Introduction</h3> Progressive loss of cell cycle control is an important feature on the adenoma-carcinoma sequence of colorectal cancer. Cyclin-dependent kinase inhibitor 1A (<i>P21</i>/<i>CDKN1A)</i> is an important target of the TGFβ signalling pathway, and it is commonly under-expressed as colorectal neoplasia develop. The aim of this study was to identify low penetrance germline variation in this gene which predisposes individuals to colorectal cancer. <h3>Methods</h3> Variation in the coding region of <i>CDKN1A</i> was determined in fifty colorectal cancer cases with a strong family history and 50 controls were tested using the Lightscanner and direct sequencing. 15 tagging SNPs around <i>CDKN1A</i> were typed in the CORGI cases and controls as part of a genome-wide analysis using the Illumina Hap550 platform in 930 cases and 960 controls performed by colleagues (Tomlinson et al 2007). Allele-specific expression of the gene was examined using quantitative reverse transcriptase PCR linked to SNPs in an upstream promoter region. <h3>Results</h3> A novel amino-acid changing variant Phe22Leu was identified in a single colorectal cancer patient. Six patients were identified in the case group and 5 in the control group with Arg31Ser. In the association study the two most significant SNPs lie in an upstream promoter region and are in linkage disequilibrium, both are risk alleles for colorectal cancer (OR 1.13; 95% CI 1.06 to 1.2). There were significant differences in expression between <i>CDKN1A</i> and the controls in 94 samples (p=0.037, Student9s t test), demonstrating linkage of these upstream polymorphisms to allele-specific expression of <i>CDKN1A</i>. <h3>Conclusion</h3> Rare variants of <i>P21</i>/<i>CDKN1A</i> are an infrequent cause of predisposition to colorectal neoplasia. A promoter region upstream of the <i>CDKN1A</i> is associated with prediposition to colorectal neoplasia, and is linked to allele-specific expression of this gene.
Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia
Authors: Ali M Zaki, Sander van Boheemen, Theo M Bestebroer, Albert D M E Osterhaus, Ron A M Fouchier
Journal: New England Journal of Medicine (2012)

A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
Neglected Infections of Poverty in the United States and Their Effects on the Brain
Authors: Peter J. Hotez
Journal: JAMA Psychiatry (2014)

A group of neglected infections are emerging as important causes of psychiatric and mental illness among vulnerable populations living in extreme poverty in the United States. These chronic infections may partially account for the achievement gap noted among socioeconomically disadvantaged students. The neglected tropical diseases (NTDs) are a group of chronic parasitic and related infections that can last decades or even the lifetime of an individual. During this time, they produce long-lasting and debilitating effects that impair productive capacity and child development. Indeed, the NTDs have actually been shown to trap people in poverty through these adverse effects. The NTDs are not rare diseases. Quite the opposite— the NTDs are now recognized as the most common afflictions of impoverished people living in low- and middle-income countries of Africa, Asia, and Latin America. The NTDs are also considered a major reason why the “bottom billion” (ie, the 1.3 billion) people living below the poverty level cannot escape poverty. In 2008, I identified a group of neglected parasitic
Impact of the Treating Institution on Survival of Patients With "Poor-Prognosis" Metastatic Nonseminoma
Authors: L. Collette
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Because metastatic nonseminomatous germ cell cancer is a rare but treatable cancer, we have explored whether there is an association between the experience of the treating institution with this disease and the long-term clinical outcome of the patients, particularly patients with a poor prognosis. METHODS: We analyzed data on 380 patients treated in one of 49 institutions participating in the European Organization for Research and Treatment of Cancer/Medical Research Council randomized trial of four cycles of bleomycin-etoposide-cisplatin followed by two cycles of etoposide-cisplatin versus three cycles of bleomycin-vincristine-cisplatin followed by three cycles of etoposide-ifosfamide-cisplatin-bleomycin, both treatment regimens given with or without filgrastim (granulocyte colony-stimulating factor). Institutions were divided into four groups based on the total number of patients entered in the trial. The groups were compared by use of the Cox proportional hazards model stratified for treatment with filgrastim and for patient prognosis as defined by the International Germ Cell Consensus Classification Group. With the use of this classification, only 65% of the patients had a poor prognosis. RESULTS: Patients treated in the 26 institutions that entered fewer than five patients into the trial had an overall survival that was statistically significantly worse (two-sided P = .010; hazard ratio = 1.85; 95% confidence interval = 1.16-3.03) than that of patients treated in the 23 institutions that entered five patients or more. Overall survival and failure-free survival were similar among institutions that entered at least five patients. The observed effect may be related to differences in adherence to the chemotherapy protocol and in the frequency and extent of surgery for residual masses, although only the differences in dose intensity achieved statistical significance. CONCLUSIONS: Patients treated in institutions that entered fewer than five patients into the trial appeared to have poorer survival than those treated in institutions that entered a larger number of patients with “poor-prognosis” nonseminoma.
NSAIDs and radiographic progression in ankylosing spondylitis Bagging big game with small arms?
Authors: Nigil Haroon, Tae-Hwan Kim, Robert D Inman
Journal: Annals of the Rheumatic Diseases (2012)

Non-steroidal anti-inflammatory drugs (NSAIDs), including Coxibs, are recommended as first-line drug treatment for patients with ankylosing spondylitis (AS) with inflammatory back pain and stiffness. Continuous treatment with NSAIDs is preferred for patients with persistently active, symptomatic disease.1

Although many young patients with AS may be at lower risk of gastrointestinal and cardiac adverse events with NSAID therapy than older patients with other rheumatic diseases, patients and physicians alike continue to raise questions about the optimal role of these agents in AS.

An earlier study examined phenylbutazone in AS and concluded that this agent not only improved the symptoms of spinal pain and stiffness, but also appeared to influence progression of new bone formation in the spine.2 A study by Wanders et al in 2005 found that the continuous use of celecoxib, in contrast with on-demand use, was also associated with less radiographic progression in AS.3 The latter was measured determining the change in the modified Stokes Ankylosing Spondylitis Spinal Score (mSASSS) over a 2-year interval. This provocative finding heightened interest in the potential disease-modifying effects of NSAIDs. However, the study of Wanders et al entailed relatively small differences in total celecoxib dose between groups. The study has awaited confirmation in other AS cohorts. We recently reported a reduced rate of progression of mSASSSs in patients who continue to take NSAIDs while being on anti-tumour necrosis factor (TNF) agents for AS.4

Two papers now published in the Annals of Rheumatic Disease provide supportive evidence that NSAIDs may slow the progression of bony change of the spine in AS.5 ,6 Data from the German Early Spondyloarthritis Inception Cohort (GESPIC) suggests that patients with AS with a high NSAID intake over 2 years demonstrated slowing of new bone formation in the spine compared with patients with low NSAID …
Sarcopenia definitions: where to draw the line? Response to Scarlata et al
Authors: M. Maddocks, S. E. Jones, S. S. C. Kon, J. L. Canavan, C. M. Nolan, A. L. Clark, M. I. Polkey, W. D.-C. Man
Journal: Thorax (2015)

We thank Scarlata et al 1 for their interest in our study 2 in which we demonstrated a 15% prevalence in stable COPD by European Working Group on Sarcopenia in Older People (EWGSOP) criteria. 3rofessor Scarlata and colleagues acknowledge these are the most commonly adopted sarcopenia criteria.Consequently, prevalence estimates in other populations 4 allow us to compare our findings beyond respiratory medicine.
ACUTE AND CHRONIC SPRAINS
Authors: W. R. Bristow
Journal: BMJ (1934)

From 1 to 2 drachms of the dilute acid (British Pharma- copoeia) are given in 5 to 10 ounces of water, to which the juice and pulp of an orange have been added.As in these residual cases the secretion of pepsin is generally reduced, a saltspoonful should be added to the mixture.The first dose should be taken fasting before breakfast, when its antiseptic action is not impaired by partial neutralization with alkaline food.The second is given as a beverage with lunch, and the third with dinner.Patients rapidly get accustomed to it, and should rarely have any difficulty in taking it regularly for,the rest of their lives. ConclusionThirty years ago Professor Knud Faber of Copenhagen came to the conclusion that achlorhydria is always secondary to gastritis, and he has maintained it ever since.When shortly after the war I first became interested in the subject I was so impressed with the constItutional factor that I was inclined to doubt whether gastritis was of any importance at all.I now realize that gastritis and constitutional factors are of equal importance.Without gastritis there is no achlorhydria, but gastritis does not cause achlorhydria unless the patient is pre- disposed by having the hyposthenic gastric constitution.Gastritis in the presence of the hypersthenic gastric constitution may lead to duodenal ulcer and gastric ulcer, and a gastric ulcer may become malignant, but achlor- hydria does not develop.It is the conjunction of the apparently trivial causes of gastritis with the byposthenic gastric constitution which leads to achlorhydria, and the conjunction of these with the constitutional predisposition to cancer which leads to carcinoma of the stomach.I expect that this is the last time there will be a discus- sion on achlorhydria, for the problem has shifted, and we must in future discuss gastritis, its causation, early diagnosis, treatment, and prophylaxis, just as we discuss nephritis rather than albuminuria.It is gastritis which causes achlorhydria, and gastritis, not achlorhydria, which causes Addison's anaemia and subacute combined degenera- tion of the cord and predisposes to carcinoma of the stomach.The prophylaxis of gastritis is the prophylaxis of these diseases.We may therefore look forward to the time when the prevention of gastritis, and, when prevention fails, its early recognition and adequate treatment, will lead to the disappearance of cancer of the stomach, which every day of the year claims over forty victims in Great- Britain.
Prognosis of Premenopausal Breast Cancer and Childbirth Prior to Diagnosis
Authors: Kelly-Anne Phillips, Roger L. Milne, Michael L. Friedlander, Mark A. Jenkins, Margaret R.E. McCredie, Graham G. Giles, John L. Hopper
Journal: Journal of Clinical Oncology (2004)

Purpose The time interval between last childbirth and subsequent breast cancer diagnosis is emerging as an important prognostic factor for premenopausal women. Patients and Methods We studied, prospectively, 750 women diagnosed with primary invasive breast cancer before age 45 years who participated in the population-based Australian Breast Cancer Family Study (ABCFS). Results Median follow-up time was 4.9 years (range, 0.8 to 10.8 years). Compared with nulliparous women, women who gave birth within 2 years prior to diagnosis were more likely to have axillary node-positive (58% v 41%; P = .01), and estrogen receptor-negative (58% v 39%; P = .005) tumors. The unadjusted hazard ratios for death were 2.3 (95% CI, 1.3 to 3.8; P = .002), 1.7 (95% CI, 1.1 to 2.6; P = .03), and 0.9 (95% CI, 0.6 to 1.5; P = .8) for patients who gave birth less than 2 years, 2 to 5 years, and 5 or more years before diagnosis, respectively. After adjusting for tumor characteristics, these hazard ratios were reduced to 1.9 (95%CI, 1.1 to 3.2; P = .02), 1.3 (95% CI, 0.8 to 2.1; P = .3), and 0.9 (95%CI, 0.5 to 1.4; P = .5). Modeling showed that, compared with nulliparous women, the mortality hazard ratio in parous women was 1.9, decreasing by 8% (95%CI, 4% to 13%; P &lt; .001) for each year between last birth and breast cancer diagnosis. Conclusion Proximity of last childbirth to subsequent breast cancer diagnosis is a predictor of mortality independent of histopathological tumor characteristics. Clinicians should be aware that women diagnosed with breast cancer within a few years following childbirth may have a worse outcome than that suggested solely by the standard histopathological prognostic factors of their cancer.
Clinical investigation and the clinical investigator: the past, present, and future.
Authors: W N Kelley
Journal: Journal of Clinical Investigation (1984)

efirst official meeting of the American Society for Clinical Investigation (ASCI) occurred on May 10, 1909, at the New Willard Hotel in Washington, DC (1). 10 papers were presented (Table I).Some of the papers covered areas of considerable importance, whereas others turned out to be of only transient interest.Nearly 50% of the membership or, if you will, 15 of the 31 members of the Society were present for this first meeting.The society was off and running, and today, we celebrate its 75th Anniversary.By whom and why was the society formed?What has been the importance of the society over the subsequent 75 years?What does the future hold?These are the questions which I will address.At a meeting of the American Medical Association held in Atlantic City in June of 1907, a small group of men stopped on the boardwalk to talk and were soon joined by Dr. Samuel J. Meltzer of New York.Dr. Meltzer was 57 at the time of this meeting.He was a Russian-born, European-educated practitioner of medicine and a well-known experimental physiologist at the Columbia College of