tbuckley/cabot-search huggingface dataset:
Solid Tumors in Children
Authors: Harold M. Maurer
Journal: New England Journal of Medicine (1978)

DURING the past two decades substantial progress has been made in the treatment of pediatric solid tumors. Improved survival is accounted for by a better understanding of the natural history of the various tumors, improved histologic classifications, new technics to define extent of disease accurately, effective chemotherapy and improved radiation, surgical and supportive therapies. The purpose of this report is to review some of the common childhood tumors, emphasizing current management and investigations.Wilms' TumorWilms' tumor is the most common intra-abdominal tumor of childhood. The median age at diagnosis is approximately 3 1/2 years. Approximately 95 per cent of . . .
The Dopamine D2 Receptor Locus as a Modifying Gene in Neuropsychiatric Disorders
Authors: David E. Comings
Journal: JAMA (1991)

<h3>Objective.</h3> —The A1 allele of the<i>Taq</i>I polymorphism of the dopamine D<sub>2</sub>receptor (<i>DRD2</i>) gene has been earlier reported to occur in 69% of alcoholics, compared with 20% of controls. Other research has reported no significant difference in the prevalence of the A1 allele in alcoholics vs controls and no evidence that the<i>DRD2</i>gene was linked to alcoholism. We hypothesized that these seemingly conflicting results might be because increases in the prevalence of the A1 allele may not be specific to alcoholism. Thus, we examined other disorders frequently associated with alcoholism or those believed to involve defects in dopaminergic neurotransmission. <h3>Design.</h3> —Case comparison study. To minimize the effect of racial differences in gene frequencies, the study was restricted to non-Hispanic whites. <h3>Setting.</h3> —Ambulatory and hospitalized patients. <h3>Results.</h3> —Among all known controls (n = 314), 77 (24.5%) carried the A1 allele. Of the 69 controls known not to be alcoholics, 10 (14.5%) carried the A1 allele. The prevalence of the A1 allele was significantly increased in patients with Tourette's syndrome (44.9%, n = 147), attention deficit hyperactivity disorder (46.2%, n = 104), autism (54.5%, n = 33), alcoholism (42.3%, n = 104), and posttraumatic stress disorder (45.7%, n = 35). After correction for multiple comparisons (requiring<i>P</i>&lt;.0009 for significance), all remained significant except posttraumatic stress disorder. The prevalence of the A1 allele was not significantly increased in patients with depression, panic attacks, Parkinson's disease, or obesity. The prevalence of the A1 allele in drug addiction and schizophrenia was only significant when compared with that of controls who were not alcoholics, and no correction was made for multiple comparisons. <h3>Conclusion.</h3> —These results suggest the A1 allele of the<i>DRD2</i>gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent. (<i>JAMA</i>. 1991;266:1793-1800)
Propionibacterium freudenreichii component 1.4-dihydroxy-2-naphthoic acid (DHNA) attenuates dextran sodium sulphate induced colitis by modulation of bacterial flora and lymphocyte homing
Authors: Y Okada
Journal: Gut (2005)

1.4-Dihydroxy-2-naphthoic acid (DHNA), a bifidogenic growth stimulator from Propionibacterium freudenreichii, is thought to have a beneficial effect as a prebiotic; however, its in vivo effect on intestinal inflammation remains unknown. The aim of this study was to determine whether oral administration of DHNA can ameliorate dextran sodium sulphate (DSS) induced colitis and to determine the possible underlying mechanisms.Colitis was induced in mice by treatment with 2.0% DSS for seven days. DHNA (0.6 or 2.0 mg/kg) was given in drinking water prior to (preventive study) or after (therapeutic study) DSS administration. Colonic damage was histologically scored, and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) expression and beta7 positive cell infiltration were determined by immunohistochemistry. mRNA levels of proinflammatory cytokines (interleukin (IL)-1beta, IL-6 and tumour necrosis factor alpha (TNF-alpha)) were determined by quantitative real time polymerase chain reaction. In addition, bacterial flora in the caecum, concentrations of short chain acids, and luminal pH were examined.DHNA improved survival rate and histological damage score in mice administered DSS in both the preventive and therapeutic studies. DHNA significantly attenuated the enhanced expression of MAdCAM-1, the increased beta7 positive cell number, and the increased mRNA levels of IL-1beta, IL-6, and TNF-alpha in DSS treated colon. In addition, the decreased number of Lactobacillus and Enterobacteriaceae induced by DSS was recovered by DHNA. Preventive effects on decrease in butyrate concentration and decrease in pH level in mice administered DSS were also observed in the DHNA preventive study.DHNA, a novel type of prebiotic, attenuates colonic inflammation not only by balancing intestinal bacterial flora but also by suppressing lymphocyte infiltration through reduction of MAdCAM-1.
Defining the role of CD2 in disease progression and overall survival among patients with completely resected stage-II to -III cutaneous melanoma
Authors: Sara Harcharik, Sebastian Bernardo, Marina Moskalenko, Michael Pan, Meera Sivendran, Heather Bell, Lawrence D. Hall, Mireia Castillo-Martín, Kelly Fox, Carlos Cordon-Cardo, Rui Chang, Shanthi Sivendran, Robert G. Phelps, Yvonne Saenger
Journal: Journal of the American Academy of Dermatology (2014)
Serum Cholesterol, Lipoproteins, and the Risk of Coronary Heart Disease
Authors: WILLIAM B. KANNEL
Journal: Annals of Internal Medicine (1971)

Risk of coronary heart disease over 14 years was examined prospectively in 2,282 men and 2,845 women according to their antecedent cholesterol and lipoprotein status. An increased risk proportional to antecedent serum cholesterol was found whether or not it was associated with elevated Sf20-400 prebeta lipoprotein. When adjustment was made for the concomitant prebeta lipoprotein concentration and other factors related both to coronary heart disease risk and to blood lipids, a residual gradient of coronary heart disease risk proportional to the serum cholesterol was still evident. On the other hand, when risk of coronary heart disease was examined according to prebeta lipoprotein concentration, adjusting for cholesterol, no residual risk gradient remained in men. In women over 50, however, prebeta lipoprotein was superior to cholesterol in discriminating potential coronary heart disease cases. Risk of coronary heart disease in men can be estimated using any of the lipids evaluated: however, none proved more useful than an accurate total serum cholesterol.
Adult-Onset Immunodeficiency in Thailand and Taiwan
Authors: Sarah K. Browne, Peter D. Burbelo, Ploenchan Chetchotisakd, Yupin Suputtamongkol, Sasisopin Kiertiburanakul, Pamela A. Shaw, Jennifer L. Kirk, Kamonwan Jutivorakool, Rifat Zaman, Li Ding, Amy P. Hsu, Smita Y. Patel, Kenneth N. Olivier, Viraphong Lulitanond, Piroon Mootsikapun, Siriluck Anunnatsiri, Nasikarn Angkasekwinai, Boonmee Sathapatayavongs, Po-Ren Hsueh, Chi-Chang Shieh, Margaret R. Brown, Wanna Thongnoppakhun, Reginald Claypool, Elizabeth P. Sampaio, Charin Thepthai, Duangdao Waywa, Camilla Dacombe, Yona Reizes, Adrian M. Zelazny, Paul Saleeb, Lindsey B. Rosen, Allen Mo, Michael Iadarola, Steven M. Holland
Journal: New England Journal of Medicine (2012)

Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown.We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained.Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering.Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.).
Patients leaving emergency departments without being seen by a physician
Authors: H. R. Hutson
Journal: JAMA (1992)

<h3>To the Editor.</h3> —In response to a very timely editorial by Dr Kellermann,<sup>1</sup>we propose adding further strategies to the five put forth by the American College of Emergency Physicians to address the problem of overcrowding of emergency departments. Not only has the cost of health care skyrocketed, the cost of obtaining a medical education has substantially increased as well. It is now common to see physicians graduating from medical school with debts greater than $100000. Many minority graduates are dissuaded from returning to work in the inner city by the financial pressures of repaying student loans and providing for their families. In many cases, the choice of specialty training itself is dictated by financial considerations rather than aptitude or interest. There are no financial incentives to encourage graduating residents with high educational debts to return to the inner city where reimbursement on a per-case basis is low
Musculoskeletal disorders and the Global Burden of Disease study
Authors: Kjersti Storheim, John-Anker Zwart
Journal: Annals of the Rheumatic Diseases (2014)

Specific data on different musculoskeletal (MSK) disorders from the Global Burden of Disease (GBD) study will be presented in this1–,3 and future issues of the journal.4–,9 MSK disorders are the second most common cause of disability worldwide, measured by years lived with disability (YLDs), with low back pain being the most frequent condition.10 Disability due to MSK disorders is estimated to have increased by 45% from 1990 to 2010, in particular osteoarthritis (OA), and is expected to continue to rise with an increasingly obese, sedentary and ageing population.10 The GBD study represents a huge and important effort that involves researchers and experts from different disciplines and countries with new statistical tools that provide us with valid information about the prevalence and burden of MSK disorders.

The specific conditions and disorders that will be addressed in this and forthcoming issues are low back pain, occupationally related low back pain, neck pain, OA, rheumatoid arthritis (RA), gout, low bone mineral density and other MSK conditions. Osteoporosis was not considered a disease in the GBD study, but bone mineral density was included in the global …
Reovirus 3 not detected by reverse transcriptase—mediated polymerase chain reaction analysis of preserved tissue from infants with cholestatic liver disease
Authors: Marilyn I. Steele, Candaca M. Marshall, Richard E. Lloyd, Vicki E. Randolph
Journal: Hepatology (1995)

Reovirus type 3 has been implicated in the origin and pathogenesis of extrahepatic biliary atresia and idiopathic neonatal hepatitis, but routine detection of this virus in hepatobiliary tissues from affected infants by culture and histological techniques has been unsuccessful. In this study, oligonucleotide primers specific to the M3 genome segment of reovirus 3 (Dearing) were used in a reverse transcriptase-mediated polymerase chain reaction technique to develop a sensitive and specific assay for the detection of reovirus 3 RNA in formalin-fixed, paraffin-embedded patient samples. Optimal reaction conditions were determined by testing infected murine tissues and preserved human liver tissue supplemented with reovirus 3. Archival specimens from 50 infants, including 14 with extrahepatic biliary atresia, 20 with idiopathic neonatal hepatitis, and 16 age-matched controls, were evaluated. Successful amplification of human albumin complementary DNA from the preserved tissues confirmed the presence of intact RNA in every patient specimen tested. Analysis of the amplification reactions by agarose gel electrophoresis and Southern blot hybridization detected the presence of reoviral RNA only once in a single patient sample. These results do not support a strong role for reovirus 3 in the development of neonatal cholestatic liver disease. The recent association of other RNA viruses of the Reoviridae family with murine liver disease and human extrahepatic biliary atresia indicates that continued investigation into a viral cause for idiopathic neonatal hepatobiliary disease is warranted.
The role of vascular capacitance in the coronary arteries.
Authors: J Lee, D E Chambers, S Akizuki, J M Downey
Journal: Circulation Research (1984)

When the left coronary artery was perfused with nonpulsatile pressure, the onset of diastole was accompanied by a capacitance overshoot in flow with an exponential decay back to a steady state. Time constant for that decay ranged from 55 msec when tone was present to 105 msec with maximal dilation. Since the transient resulted from a fall in tissue pressure, this represents an estimation of intramural arterial capacitance only. Transients in perfusion pressure, which would also affect epicardial arteries, yielded similar time constants. We concluded that most of the coronary capacitance resides in the small intramural vessels. Analysis of transients yielded a value for capacitance of between 0.01 and 0.05 ml/mm Hg per 100 g. We then used the data from the transients to construct coronary pressure flow curves which were free of any back flow from capacitance. When coronary tone was present, the curves indicated that flow ceased at 30 mm Hg. With maximal dilation, flow ceased at only 18 mm Hg. Long diastoles in those same hearts indicated that flow ceased at about 10 mm Hg higher pressure. Although capacitance causes critical closing pressure as determined by a long diastole to be artifactually high, critical closing pressure is still appreciable in the heart, and tone dependent. Finally, three computer models were built, one of which included only small vessel capacitances, the second, only vascular waterfalls, and the third, both of the above. Only model 3 was capable of reproducing the flow patterns which were actually seen.
Major histocompatibility locus genetic markers of beryllium sensitization and disease
Authors: C. Saltini, L. Richeldi, M. Losi, M. Amicosante, C. Voorter, E. van den Berg-Loonen, R.A. Dweik, H.P. Wiedemann, D.C. Deubner, C. Tinelli
Journal: European Respiratory Journal (2001)

Hypersensitivity to beryllium (Be) is found in 1–16% of exposed workers undergoing immunological screening for beryllium disease using the beryllium lymphocyte proliferation test (BeLPT). However, only ∼50% of BeLPT-positive workers present with lung granulomas ( i.e. berylliosis). As berylliosis is associated with the human leukocyte antigen (HLA)-DP supratypic marker DPGlu69, the authors asked whether this marker is differentially associated with disease presentation. A population of 639 workers from a beryllium factory undergoing BeLPT screening was evaluated in a nested case-control study for the prevalence of HLA-DPGlu69, the HLA-DPB1, HLA-DQ and HLA-DR alleles and of the biallelic tumour necrosis factor (TNF)-;α polymorphism TNF-;α-;308 in 23 individuals presenting as “sensitized” ( i.e. BeLPT-positive without lung granulomas) and in 22 presenting as “diseased” ( i.e. BeLPT-positive with granulomas in the lung biopsy). The HLA-DPGlu69 marker was associated with “disease” (odds ratio (OR) 3.7, p=0.016, 95% confidence interval (CI) 1.4–10.0), whilst the high TNF-;α production-related TNF-;α-;308*2 marker was associated with both a positive BeLPT (OR 7.8, corrected p&lt;0.0001, 95% CI 3.2–19.1) with no difference between “sensitization” and “disease”. Furthermore, the HLA-DRArg74 marker was associated with “sensitization” without disease (OR 3.96, p=0.005, 95% CI 1.5–10.1). The data indicate that tumour necrosis factor-;α, human leukocyte antigen-DR and human leukocyte antigen-DP markers play different roles in beryllium sensitization and granuloma formation in beryllium-exposed workers.
Vulnerability as a Function of Individual and Group Resources in Cumulative Risk Assessment
Authors: Peter L. deFur, Gary W. Evans, Elaine A. Cohen Hubal, Amy D. Kyle, Rachel A. Morello-Frosch, David R. Williams
Journal: Environmental Health Perspectives (2007)

BackgroundThe field of risk assessment has focused on protecting the health of individual people or populations of wildlife from single risks, mostly from chemical exposure. The U.S. Environmental Protection Agency recently began to address multiple risks to communities in the "Framework for Cumulative Risk Assessment" [EPA/630/P02/001F. Washington DC:Risk Assessment Forum, U.S. Environmental Protection Agency (2003)].Simultaneously, several reports concluded that some individuals and groups are more vulnerable to environmental risks than the general population. However, vulnerability has received little specific attention in the risk assessment literature.ObjectiveOur objective is to examine the issue of vulnerability in cumulative risk assessment and present a conceptual framework rather than a comprehensive review of the literature. In this article we consider similarities between ecologic and human communities and the factors that make communities vulnerable to environmental risks.DiscussionThe literature provides substantial evidence on single environmental factors and simple conditions that increase vulnerability or reduce resilience for humans and ecologic systems. This observation is especially true for individual people and populations of wildlife. Little research directly addresses the topic of vulnerability in cumulative risk situations, especially at the community level. The community level of organization has not been adequately considered as an end point in either human or ecologic risk assessment. Furthermore, current information on human risk does not completely explain the level of response in cumulative risk conditions. Ecologic risk situations are similarly more complex and unpredictable for cases of cumulative risk.ConclusionsPsychosocial conditions and responses are the principal missing element for humans. We propose a model for including psychologic and social factors as an integral component of cumulative risk assessment.
Cloned platelet thrombin receptor is necessary for thrombin-induced platelet activation.
Authors: D T Hung, T K Vu, V I Wheaton, K Ishii, S R Coughlin
Journal: Journal of Clinical Investigation (1992)

Platelet activation by thrombin is critical for hemostasis and thrombosis. Structure-function studies with a recently cloned platelet thrombin receptor suggest that a hirudin-like domain in the receptor's extracellular amino terminal extension is a thrombin-binding determinant important for receptor activation. We now report that a peptide antiserum to this domain is a potent and specific antagonist of thrombin-induced platelet activation. This study demonstrates that the cloned platelet thrombin receptor is necessary for platelet activation by thrombin, and provides a strategy for developing blocking monoclonal antibodies of potential therapeutic value.
Activity and tolerability of the Bruton's tyrosine kinase (Btk) inhibitor PCI-32765 in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Interim results of a phase Ib/II study.
Authors: J. C. Byrd, K. A. Blum, J. A. Burger, S. E. Coutre, J. P. Sharman, R. R. Furman, I. W. Flinn, B. W. Grant, D. A. Richards, W. Zhao, N. A. Heerema, A. J. Johnson, R. Izumi, A. Hamdy, S. M. O'Brien
Journal: Journal of Clinical Oncology (2011)

6508 Background: Btk is essential to B-cell development and function. Btk is highly-expressed in CLL and its inhibition by the potent irreversible inhibitor PCI32765 (P) promotes apoptosis and inhibition of cytokine, chemokine, microenvironment-mediated signaling, proliferation, and chemotaxis ex vivo. We report interim results of a large Phase Ib/II trial of P in CLL/SLL. Methods: Two cohorts (previously untreated [PU] >65 yrs old and relapsed/refractory [R/R] disease following at least 2 prior therapies [Rx] including fludarabine) of CLL patients (pts) were treated with oral P administered daily for 28-d cycles until progression of disease (PD). Doses of 420mg (24 PU and 27 R/R) and 840 QD (31 R/R) were examined. Results: Of the 78 pts enrolled, data from the first 39 pts will be sufficiently mature as of May 2011 to assess IWCLL2008/Cheson response criteria. R/R pts had a median age of 64, 37% were Rai III/IV, and median of 3 (range 2-10) prior Rx. 87% had at least one poor-risk molecular feature: del(17p)-30%, del(11q)-21%, IgVH un-mutated 70%. Treatment has been well tolerated with grade >3 AEs potentially related to P in 26% of pts. >Gr 3 cytopenias have been noted in <5% of pts. No pts have had LFT elevations. In evaluable pts with lymphadenopathy, the rate of nodal response (LNR; >50% reduction in target lesions) is 89% (25/28 pts). An increase in absolute lymphocyte counts (ALC) occurred in 75% of pts and has decreased over time in the vast majority. At a median follow-up of 4 months, 17 (44%) have a PR (n=15, 39%) or CR/CRu (n=2, 5%). Response has been similar in all genomic groups. Notably, 4 of 12 pts with del(17p) have responded and 7 others remain on P Rx with improving SD. Mature response data will be updated. At a median follow-up of 4 months, 34/39 pts in the 420 mg cohort remain on P therapy with only one PD. Conclusions: PCI32765 is highly active and well tolerated in CLL/SLL pts irrespective of high risk genomic abnormalities. Although follow-up is short, the high response rate and very low progression rate suggests that PCI-32765 may be an important new targeted treatment approach for CLL pts, including those with del(17p).