tbuckley/cabot-search huggingface dataset:
Effect of Cyproheptadine on Appetite and Weight Gain in Adults
Authors: Rudolf E. Noble
Journal: JAMA (1969)

Cyproheptadine (Periactin) hydrochloride, a histamine and serotonin antagonist, was compared with placebo for effectiveness in producing appetite stimulation and weight gain in healthy, underweight, adults. Increase in appetite and weight was significantly greater statistically in those who received cyproheptadine. Drowsiness was a common transient side effect of cyproheptadine. There were no significant alterations in laboratory values following cyproheptadine administration.
Optimizing Endocrine Therapy for Breast Cancer
Authors: Eric P. Winer
Journal: Journal of Clinical Oncology (2005)

to patients in place of tamoxifen, or as part of a sequential treatment strategy. Further analysis of completed trials, as well as results of ongoing and future studies, will provide critical answers that may translate into further improvements in care for postmenopausal women with receptorpositive disease. More than 2,000 postmenopausal women are diagnosed with receptor-positive disease each week in the United States alone; the impact of any improvements in the care of these patients could have significant public
Clinical Care of Two Patients with Ebola Virus Disease in the United States
Authors: G. Marshall Lyon, Aneesh K. Mehta, Jay B. Varkey, Kent Brantly, Lance Plyler, Anita K. McElroy, Colleen S. Kraft, Jonathan S. Towner, Christina Spiropoulou, Ute Ströher, Timothy M. Uyeki, Bruce S. Ribner
Journal: New England Journal of Medicine (2014)

West Africa is currently experiencing the largest outbreak of Ebola virus disease (EVD) in history. Two patients with EVD were transferred from Liberia to our hospital in the United States for ongoing care. Malaria had also been diagnosed in one patient, who was treated for it early in the course of EVD. The two patients had substantial intravascular volume depletion and marked electrolyte abnormalities. We undertook aggressive supportive measures of hydration (typically, 3 to 5 liters of intravenous fluids per day early in the course of care) and electrolyte correction. As the patients' condition improved clinically, there was a concomitant decline in the amount of virus detected in plasma.
New insight in the pathobiology of hepatitis B virus infection
Authors: Maura Dandri, Stephen Locarnini
Journal: Gut (2012)

Chronic hepatitis B virus (HBV) infection remains a major health burden and the main risk factor for the development of hepatocellular carcinoma worldwide. However, HBV is not directly cytopathic and liver injury appears to be mostly caused by repeated attempts of the host's immune responses to control the infection. Recent studies have shown that the unique replication strategy adopted by HBV enables it to survive within the infected hepatocyte while complex virus–host interplays ensure the virus is able to fulfil its replication requirements yet is still able to evade important host antiviral innate immune responses. Clearer understanding of the host and viral mechanisms affecting HBV replication and persistence is necessary to design more effective therapeutic strategies aimed at improving the management of patients with chronic HBV infection to eventually achieve viral eradication. This article focuses on summarising the current knowledge of factors influencing the course of HBV infection, giving emphasis on the use of novel assays and quantitative serological and intrahepatic biomarkers as tools for predicting treatment response and disease progression.
PWE-257 The role of RDH10 and RALDH enzymes in retinoic acid-mediated immune regulation by antigen presenting cells in the human intestine
Authors: T J Sanders, N E McCarthy, E M Giles, J O Lindsay, A J Stagg
Journal: Gut (2012)

<h3>Introduction</h3> All-trans retinoic acid (RA) has emerged as an important immunoregulatory molecule with specific functions in the intestine. RA is generated enzymatically by the sequential action of alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (RALDH) enzymes. In the mouse, RALDH expression is confined to CD103+ intestinal dendritic cells (DC) giving this subset the unique ability to mediate RA-dependent functions such as the imprinting of gut tropism on T cells. RALDH activity is downregulated in mouse models of inflammatory bowel disease (IBD) but little is known about its role in human intestine. The aim of this study was to assess RA-dependent immune regulation by human intestinal antigen presenting cells (APC). <h3>Methods</h3> Lamina propria mononuclear cells (LPMC) were extracted from intestinal biopsies by enzymatic digestion and analysed by multicolour flow cytometry. Purified subsets of intestinal APC were obtained by immunomagnetic or FACS sorting. Expression of <i>ADH</i> and <i>RALDH</i> enzymes was quantified by quantitative RT-PCR and RALDH activity assessed using the Aldefluor assay. The ability to induce the gut homing receptor α4β7 on T cells was assessed by flow cytometry following stimulation of CFSE-labelled naïve CD4+ T cells. <h3>Results</h3> Induction of the gut homing receptor α4β7 on human T cells was RA dependent. Intestinal myeloid APC were potent stimulators of naïve CD4+ T cells and induced high levels of α4β7. Both of these activities were attributed to the CD103+ APC fraction. However, analysis of ex vivo intestinal populations revealed RALDH activity in all myeloid APC populations studied: CD103+ and CD103− DC identified as HLA−DR+CD11c+Lin− (Lin=anti-CD3,14,16,19,34) as well as HLA−DR+CD11c+Lin+ monocyte-like cells. Lymphocytes had little or no Aldefluor activity. Comparison of intestinal DC from healthy controls and IBD patients showed similar RALDH activity in inflamed and non-inflamed tissue. RALDH activity was equivalent in CD103+ and CD103− DC. In contrast, the ADH RDH10 was expressed at levels 4.5-fold higher in CD103+ DC. <h3>Conclusion</h3> As in the mouse, RA-mediated induction of α4β7 is a property of the CD103+ subset of intestinal DC. However in divergence from murine data, this property is associated with restricted expression of the ADH enzyme RDH10 rather than “downstream” RALDH enzymes. These data imply that RA availability is regulated differently in mice and man, with expression of RDH10 providing an important control point in humans. <h3>Competing interests</h3> None declared.
Treatment of active spondyloarthropathy with infliximab, the chimeric monoclonal antibody to tumour necrosis factor α
Authors: F Van den Bosch, D Baeten, E Kruithof, F De Keyser, H Mielants, E M Veys
Journal: Annals of the Rheumatic Diseases (2001)

The spondyloarthropathies (SpA) are a group of chronic autoimmune disorders of the joint.1 Entities belonging to this group are ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, arthritis related to inflammatory bowel diseases such as Crohn's disease (CD) and ulcerative colitis, and arthritis associated with acute anterior uveitis. Patients who fulfil the European Spondyloarthropathy Study Group (ESSG) classification criteria,2 but who do not belong to one of the subtypes described above are termed undifferentiated spondyloarthropathy.3 

This common rheumatic condition has a global prevalence of 0.5–1%, with, however, important racial and geographical differences and a clear male predominance. Juveniles as well as adults can be affected by one of the diseases included in the SpA group. All the diseases in this group have common clinical, radiological, and genetic features. The typical hallmarks of this disease group are sacroiliitis, spondylitis, peripheral arthritis, and enthesitis. The spondylitis typically affects the insertion of the collateral ligaments with syndesmophyte formation and the zygapophysial joints. The peripheral arthritis is asymmetrical and mainly affects the legs. The synovitis may be self limiting or chronic with joint destruction. Enthesitis, mostly localised at the Achilles tendon and plantar fascia is also typical for this disease entity.

A specific feature, mostly seen in psoriatic arthritis or inflammatory bowel disease, is dactylitis, where different small joints on one finger or toe are affected. In an important number of cases, subclinical gut inflammation with pathological findings resembling CD can be found, its presence ranging from 25 to 75% depending upon the type of SpA.4 Some of these patients (undifferentiated SpA with histological evidence of chronic gut inflammation) may eventually develop overt CD at a five years' follow up.5 6 In repeat ileocolonoscopy studies, clinical remission of articular symptoms was consistently associated with normalisation of gut histology, whereas …
Skin and bones. II
Authors: Seth J. Orlow, Kalman L. Watsky, Jean L. Bolognia
Journal: Journal of the American Academy of Dermatology (1991)

Skin disorders in which a radiiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sacoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acrosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. The first part of this review, published in the August 1991 issue of this JOURNAL, dealt with the first two categories; part II dicusses categories 3 through 8. Skin disorders in which a radiiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sacoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acrosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. The first part of this review, published in the August 1991 issue of this JOURNAL, dealt with the first two categories; part II dicusses categories 3 through 8.
Reconstitution of the subclass-specific expression of CD4 in thymocytes and peripheral T cells of transgenic mice: identification of a human CD4 enhancer.
Authors: M D Blum, G T Wong, K M Higgins, M J Sunshine, E Lacy
Journal: The Journal of Experimental Medicine (1993)

During thymic maturation, CD4-CD8-TCR- immature thymocytes differentiate through a CD4+CD8+TCRlo intermediate into two functionally distinct mature T cell subsets: helper T cells expressing CD4 and a major histocompatibility complex (MHC) class II-restricted T cell receptor (TCR), and cytotoxic T cells expressing CD8 and and MHC class I-restricted TCR. The mutually exclusive expression of CD4 and CD8 is maintained in the periphery during expansion of these mature T cell subsets. To elucidate the mechanisms controlling CD4 and CD8 expression on differentiating thymocytes and mature peripheral T cells, we have examined the expression of human CD4 gene constructs in the lymphoid tissues of transgenic mice. Our analyses demonstrate that sequences contained within or closely linked to the human CD4 gene are sufficient to reconstitute the appropriate regulation of human CD4 expression on all thymocyte and mature peripheral T cell subsets. Specifically, appropriate developmental regulation was dependent on two sets of sequences, one contained within a 1.3-kb restriction fragment located 6.5 kb upstream of the human CD4 gene, and the other present within or immediately flanking the gene. Nucleotide sequence analysis identified the 1.3-kb restriction fragment as the likely human homologue of an enhancer found 13 kb upstream of the mouse CD4 transcription initiation site. The human CD4 transgenic mice provide a useful system for the identification and characterization of additional sequence elements that participate in human CD4 gene regulation and for the elucidation of regulatory mechanisms governing the developmental program mediating the maturation of the CD4+ and CD8+ peripheral T cell subsets.
Body mass index as predictor for asthma: a cohort study of 118,723 males and females
Authors: V. Hjellvik, A. Tverdal, K. Furu
Journal: European Respiratory Journal (2010)

The objective of the present study was to quantify the relationship between body mass index (BMI; in kilogrammes per metre squared) and asthma in middle-aged males and females, and to evaluate change in BMI as a risk factor for asthma. Asthma incidence was estimated from data on redeemed prescriptions of anti-asthmatic drugs during the period 2004–2007, retrieved from the nationwide Norwegian Prescription Database. BMI was measured during health surveys in 1994–1999 in &gt;100,000 individuals born during 1952–1959. Change in BMI was based on self-report. Relative risks were estimated using Poisson regression. The relative risk associated with a 3-unit increase in BMI ranged from 1.14 (95% confidence interval 1.10–1.18) in current smokers to 1.27 (1.22–1.32) in never-smokers after adjusting for confounders. The relative risk associated with a 3-unit increase in BMI was 1.21 (1.16–1.26) after adjusting for confounders, including sex, smoking and BMI. Asthma incidence, as measured by anti-asthmatic drug use, was positively related to both BMI and change in BMI. For BMI, the association was stronger for never-smokers than for ex-smokers and current smokers.
NOS and COX isoforms and abnormal microvessel responses to CO2 and H+ in hyperoxia-injured lungs
Authors: K. Naoki, H. Kudo, K. Suzuki, K. Takeshita, N. Miyao, M. Ishii, N. Sato, Y. Suzuki, H. Tsumura, K. Yamaguchi
Journal: European Respiratory Journal (2002)

The aim of the present study was to compare microvessel responses to hypercapnic and isocapnic acidosis in hyperoxia-injured lungs and to assess the role of constitutive and inducible forms of nitric oxide synthase (NOS) and cyclo-oxygenase (COX). Real-time confocal luminescence microscopy was used to measure changes in the diameter of acinar arterioles, venules and capillaries in response to stimulation with hypercapnic and isocapnic acidosis in isolated rat lungs injured by 90% oxygen exposure for 48 h. Observations were made with and without inhibition of constitutive (endothelial constitutive NOS (ecNOS) and COX‐1) and inducible isoforms (iNOS and COX‐2) of NOS and COX. Upregulation of NOS was assessed by measuring enzyme levels in lung homogenates by Western blot analysis and enhancement of the COX-related pathway was judged from perfusate concentrations of 6‐ketoprostaglandin F 1α . ecNOS and COX‐1, but not iNOS and COX‐2, were upregulated in hyperoxia-injured lungs. The nitric oxide produced by ecNOS attenuated COX‐1 activity in injured arterioles and venules, but carbon dioxide enhanced it, leading to paradoxical dilatation of these microvessels under hypercapnic conditions with ecNOS inhibition. Although a high hydrogen ion concentration was unnecessary for excitation of COX‐1, venule constriction in response to H + was enhanced by COX‐1 inhibition. Constitutive, but not inducible, isoforms of cyclo-oxygenase and nitric oxide synthase play an important role in abnormal microvessel responses to carbon dioxide and hydrogen ions in hyperoxia-injured lungs.
Minimal Disseminated Disease in Childhood T-Cell Lymphoblastic Lymphoma: A Report From the Children's Oncology Group
Authors: Elaine Coustan-Smith, John T. Sandlund, Sherrie L. Perkins, Helen Chen, Myron Chang, Minnie Abromowitch, Dario Campana
Journal: Journal of Clinical Oncology (2009)

PURPOSE Disease dissemination to the bone marrow is detected at diagnosis in approximately 15% of children with T-cell lymphoblastic lymphoma (T-LL). It is unclear whether the remaining patients have submicroscopic systemic disease and, if so, what is the clinical significance of this finding. PATIENTS AND METHODS Using a flow cytometric method that can detect one T-LL cell among 10,000 normal cells, we examined bone marrow and peripheral-blood samples collected from 99 children with T-LL at diagnosis, as well as blood samples collected from 42 patients during treatment. Results In 71 (71.7%) of the 99 marrow samples obtained at diagnosis, T-LL cells represented 0.01% to 31.6% (median, 0.22%) of mononuclear cells; 57 of the 71 T-LL-positive samples were from patients with stage II/III disease. Results of studies in bilateral marrow aspirates were highly concordant. Two-year event-free survival (EFS) was 68.1% +/- 11.1% (SE) for patients with > or = 1% T-LL cells in bone marrow versus 90.7% +/- 4.4% for those with lower levels of marrow involvement (P = .031); EFS for patients with > or = 5% lymphoblasts was 51.9% +/- 18.0% (P = .009). T-LL cells were as prevalent in blood as in marrow; monitoring residual T-LL cells in blood during remission induction therapy identified patients with slower disease clearance. CONCLUSION More than two thirds of children with T-LL have disseminated disease at diagnosis, a proportion much higher than previously demonstrated. Measurements of disease dissemination at diagnosis might provide useful prognostic information, which can be further refined by monitoring response to therapy through blood testing.
THE ACUTE PSYCHIATRIC TYPE OF EPIDEMIC ENCEPHALITIS
Authors: Irving J. Sands
Journal: American Journal of Psychiatry (1928)

Epidemic encephalitis is an infectious disease of as yet unknown etiology, but of a well-established pathology. The cerebro-spinal nervous system, especially the brain, bears the brunt of the infection. The anatomical picture is characterized by marked congestion and edema, infiltration of the Virchow-Robin lymph spaces by lymphocytes and plasma cells; distension and occasional rupture of vessels resulting in hemorrhage; moderate cloudy swelling of the ganglion cells with chromatolysis, satillitosis and occasionally neurononphagy; and moderate neuroglia reaction. The pathological process is a changing and progressive one. The mental picture results from the action of the encephalitic virus and inflammatory exudates upon the nerve tissue. The clinical reaction, therefore, may be that of an acute organic psychosis in which there is a constant changing of symptoms. Occasionally the toxemia may bring to the surface deeply rooted mental conflicts, adding a psychogenic coloring to the presenting symptoms. The encephalitic virus may first attack those parts of the brain that control the highest psychic processes (frontal lobes) and may produce a psychosis as the earliest clinical manifestation. The early recognition of these cases are of tremendous medical and sociological importance.
Lessons Learned From an Unusual Presentation of CD3<sup>+</sup>, CD56<sup>−</sup> T-Cell Large Granular Lymphocyte Leukemia
Authors: Rebecca J. Lee, Nicole Ritz, Angela Chi-Ying Chan, Stuart P. Berzins, Neil Came, Nigel Curtis, Andrew Lim, Simon James Harrison
Journal: Journal of Clinical Oncology (2010)
Nitric Oxide-Induced Decrease in Calcium Sensitivity of Resistance Arteries Is Attributable to Activation of the Myosin Light Chain Phosphatase and Antagonized by the RhoA/Rho Kinase Pathway
Authors: Steffen-Sebastian Bolz, Lukas Vogel, Daniel Sollinger, Roland Derwand, Cor de Wit, Gervaise Loirand, Ulrich Pohl
Journal: Circulation (2003)

NO-induced dilations in resistance arteries (RAs) are not associated with decreases in vascular smooth muscle cell Ca2+. We tested whether a cGMP-dependent activation of the smooth muscle myosin light chain phosphatase (MLCP) resulting in a Ca2+ desensitization of the contractile apparatus was the underlying mechanism and whether it could be antagonized by the RhoA pathway.The Ca2+ sensitivity of RA was assessed as the relation between changes in diameter and [Ca2+]i in depolarized RA (120 mol/L K+) exposed to stepwise increases in Ca2+ex (0 to 3 mmol/L). Effects of 10 micromol/L sodium nitroprusside (SNP) on Ca2+ sensitivity were determined before and after application of the soluble guanylate cyclase inhibitor ODQ (1 micromol/L) and the MLCP inhibitor calyculin A (120 nmol/L) and in presence of the RhoA-activating phospholipid sphingosine-1-phosphate (S1P, 12 nmol/L). SNP-induced dilations were also studied in controls and in RAs pretreated with the Rho kinase inhibitor Y27632 or transfected with a dominant-negative RhoA mutant (N19RhoA). Constrictions elicited by increasing Ca2+ex were significantly attenuated by SNP, which, however, left associated increases in [Ca2+]i unaffected. This NO-induced attenuation was blocked by ODQ, calyculin A, and S1P. The S1P-induced translocation of RhoA indicating activation of the GTPase was not reversed by SNP. Inhibition of RhoA/Rho kinase by N19RhoA or Y27632 significantly augmented SNP-induced dilations.NO dilates RA by activating the MLCP in a cGMP-dependent manner, thereby reducing the apparent Ca2+ sensitivity of the contractile apparatus. MLCP inactivation via the RhoA/Rho kinase pathway antagonizes this Ca2+-desensitizing effect that, in turn, can be restored using RhoA/Rho kinase inhibitors.
Cigarette Smoking and Microsatellite Instability: Causal Pathway or Marker-Defined Subset of Colon Tumors?
Authors: A. I. Neugut
Journal: JNCI Journal of the National Cancer Institute (2000)

When the average person thinks of cigarette smoking and cancer, the cancers that come to mind are those of the lung and upper aerodigestive tract. Cancer researchers have also long recognized the etiologic association of cigarette smoking with a number of other cancers, such as those of the bladder and pancreas. Until quite recently, however, colon cancer, one of the most common cancers in the United States, was not recognized as being associated with cigarette smoking, this despite the fact that numerous studies (1–3) consistently found an association between cigarette smoking and adenomas, the precursor lesions for most cases of colon cancer.
Randomized Controlled Trial of Clopidogrel plus Aspirin to Prevent Hemodialysis Access Graft Thrombosis
Authors: James S. Kaufman, Theresa Z. O’Connor, Jane Hongyuan Zhang, Robert E. Cronin, Louis D. Fiore, Michael B. Ganz, David S. Goldfarb, Peter N. Peduzzi
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden. Experimental and clinical models suggest a role for antiplatelet agents in the prevention of thrombosis. The study was designed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis. The study was a randomized, double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers. Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were randomized to receive either double placebos or aspirin (325 mg) and clopidogrel (75 mg) daily. Participants were to be monitored while receiving study medications for a minimum of 2 yr. The study was stopped after randomization of 200 participants, as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy. The cumulative incidence of bleeding events was significantly greater for those participants, compared with participants receiving placebos [hazard ratio, 1.98; 95% confidence interval (CI), 1.19 to 3.28; P = 0.007]. Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event (P = 0.006). There was no significant benefit of active treatment in the prevention of thrombosis (hazard ratio, 0.81; 95% CI, 0.47 to 1.40; P = 0.45), although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis (hazard ratio, 0.52; 95% CI, 0.22 to 1.26; P = 0.14). In the hemodialysis population, therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis. E-mail: [email protected]