tbuckley/cabot-search huggingface dataset:
OC-035 Mechanism of Lactose Intolerance in Irritable Bowel Syndrome: Role of Anxiety, Mucosal Immunity and Visceral Hypersensitivity
Authors: Y Long, J Yang, Y Zhu, Y Cong, H Chu, N Dai, M Fried, M Fox
Journal: Gut (2013)

Introduction Many patients, especially those with Irritable Bowel Syndrome (IBS), report food intolerance; however the mechanism underlying these “functional digestive symptoms” is unknown. We assessed the role of psychological factors, mucosal immune activation and visceral sensitivity on the development of lactose intolerance (LI) after ingestion of 20g lactose in IBS patients and healthy controls (HCs) with lactase deficiency: a validated, clinical experimental model of intolerance to poorly absorbed, fermentable foods (Yang et al Clin Gastro Hep 2013 in publication). Methods IBS-D patients meeting Rome III criteria (n = 277) and age/sex matched HCs (n = 64) underwent a 20g lactose hydrogen breath test (LHBT) with measurement of hydrogen production, abdominal distention, and LI symptoms. Hospital Anxiety and Depression Score assessed psychologic state. Barostat measured rectal sensitivity. Additionally, 55 IBS-D patients and 18 HCs completed colonoscopy with colon and terminal ileum (TI) biopsies for quantification of mast cells (MCs), T lymphocytes, and enterochromaffin cells (ECC). Results Hydrogen production and distention were similar in IBS patients and HCs during LHBT; however LI symptoms were more frequent in IBS (54% vs. 28%, P < 0.001), including bloating (39% vs . 14%, P < 0.001), borborygmi (39% vs. 22%, P = 0.010), pain (31% vs. 11%, P = 0.001) and diarrhoea (29% vs. 9%, P = 0.001). IBS patients were more anxious (p < 0.001) and had higher rectal sensitivity than HCs ( P = 0.001). Multivariate analysis indicated that hydrogen production increased the likelihood of bloating (OR2.2 (95%CI 1.1–4.4), P = 0.028) and borborygmi (OR12.4 (3.3–45.8), P < 0.001), but not objective distention ( P = 0.673). Visceral hypersensitivity also associated with bloating (OR6.6 (1.7–25.0), P = 0.005) and total symptom score (OR3.7 (1.3–10.9, P = 0.014). A planned subanalysis showed that, compared to IBS patients with no symptoms, those with LI were more anxious (p = 0.045) and more likely to have visceral hypersensitivity (p < 0.001). In those that had colonoscopy, IBS patients with LI (25/55 (45%)) had increased MCs (p < 0.006), T-cells and ECC (both p < 0.05) in proximal colonic and TI mucosa compared to patients without LI and HCs. Multivariate analysis indicated that total LI symptom score was associated with anxiety (r = 0.519, P < 0.001), MCs in terminal ileum (r = 0.650, P < 0.001) and visceral sensitivity (r = 0.629, P < 0.001). Conclusion Gas production and sensitivity to luminal distension both contribute to digestive symptoms after lactose ingestion in patients with lactase deficiency. IBS-D patients with LI are characterised by anxiety, evidence of mucosal immune activation and visceral hypersensitivity. Disclosure of Interest None Declared
Effect of the Proprotein Convertase Subtilisin/Kexin 9 Monoclonal Antibody, AMG 145, in Homozygous Familial Hypercholesterolemia
Authors: Evan A. Stein, Narimon Honarpour, Scott M. Wasserman, Feng Xu, Rob Scott, Frederick J. Raal
Journal: Circulation (2013)

Background— Homozygous familial hypercholesterolemia is a rare, serious disorder with a substantial reduction in low-density lipoprotein (LDL) receptor function, severely elevated LDL cholesterol, cardiovascular disease, and often death in childhood. Response to conventional drug therapies is modest. Monoclonal antibodies to proprotein convertase subtilisin/kexin 9 (PCSK9) reduce LDL cholesterol in heterozygous familial hypercholesterolemia. The effect in homozygous familial hypercholesterolemia is unknown and uncertain. We evaluated the efficacy and safety of AMG 145 in an open-label, single-arm, multicenter, dose-scheduling pilot study in patients with homozygous familial hypercholesterolemia. Methods and Results— Eight patients with LDL receptor–negative or –defective homozygous familial hypercholesterolemia on stable drug therapy were treated with subcutaneous 420 mg AMG 145 every 4 weeks for ≥12 weeks, followed by 420 mg AMG 145 every 2 weeks for an additional 12 weeks. All patients completed both treatment periods. Mean change from baseline in LDL cholesterol at week 12 was −16.5% (range, 5.2% to −43.6%; P =0.0781) and −13.9% (range, 39.9% to −43.3%; P =0.1484) with 4- and 2-week dosing, respectively. No reduction was seen in the 2 receptor-negative patients. Over the treatment periods, mean±SD LDL cholesterol reductions in the 6 LDL receptor–defective patients were 19.3±16% and 26.3±20% with 4- and 2-week dosing, respectively ( P =0.0313 for both values), ranging from 4% to 48% with 2-week dosing. No serious side effects were reported. Conclusion— This study demonstrates significant and dose-related LDL cholesterol lowering with a PCSK9 monoclonal antibody in homozygous familial hypercholesterolemia patients with defective LDL receptor activity but no reduction in those who were receptor negative. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT01588496 and NCT01624142.
Intensive care unit environment may affect the course of delirium
Authors: Irene J. Zaal, Carolina F. Spruyt, Linda M. Peelen, Maarten M. J. van Eijk, Rens Wientjes, Margriet M. E. Schneider, Jozef Kesecioglu, Arjen J. C. Slooter
Journal: Intensive Care Medicine (2012)
Time for a fresh look at complementary medicine
Authors: E. Baldwin
Journal: BMJ (2003)

Spondyloarthritis (SpA) encompasses a group of inflammatory rheumatic diseases that share clinical and imaging characteristics as well as a common genetic basis. These diseases can affect 0.20–1.6% of the general population, limiting functioning and affecting the quality of life of patients. Considering the patient perspective in the management of the disease and ensuring patients are sufficiently prepared to participate in decision making is critical to treatment success, as well as for optimal health outcomes. The overall picture of impairments, limitations, and restrictions in activities or social participation for patients with SpA is not adequately assessed in SpA-specific instruments. Therefore, it is important to measure the broader range of impairments that can affect patients with SpA and integrate these into a single measure of overall functioning in daily life. The Assessment of SpondyloArthritis international Society Health Index (ASAS HI) is a recently introduced health instrument for evaluating SpA based on the International Classification of Functioning, Disability and Health (ICF) that could cover a good part of the health metric needs in SpA. This review addresses its origins, measurement properties, and use in routine clinical practice, as well as its prospects for future use.
Distinct pathways of LPS-induced NF-κB activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP
Authors: Evangelos Andreakos, Sandra M. Sacre, Clive Smith, Anna Lundberg, Serafim Kiriakidis, Tim Stonehouse, Claudia Monaco, Marc Feldmann, Brian M. Foxwell
Journal: Blood (2003)
Pathological features of coronary arteries in children with Kawasaki disease in which coronary arterial aneurysm was absent at autopsy. Quantitative analysis.
Authors: T Fujiwara, H Fujiwara, H Nakano
Journal: Circulation (1988)

Coronary arteries in six children who had Kawasaki disease but lacked coronary arterial aneurysms were examined. Four children died of myocarditis at the acute stage, and two children died of bacterial sepsis or as a result of an occurrence during cineangiography at the healed stage. Twenty-one children without Kawasaki disease were examined as controls. The six children with Kawasaki disease had no thrombi, recanalization, or stenosis greater than 50% in the major coronary arteries. Three patients had dilatation of the major coronary arteries at the acute stage. Two of the three patients died during the acute stage, and autopsy showed slight dilatation of coronary arteries and abnormal intimal thickening due to panvasculitis. In the third child, who died at the healed stage, dilatation of the coronary arteries detected by two-dimensional echocardiography at the acute stage had disappeared at the healed stage. No dilatation of the major coronary arteries was seen at autopsy. However, abnormal fibrous intimal thickening of the major coronary arteries without inflammatory changes was found. The other three patients had no dilatation of the major coronary arteries at the acute stage. Two patients died at the acute stage, and slight inflammation without abnormal intimal thickening was seen in the intima and the adventitial area. In the third patient, who died during the healed stage, two-dimensional echocardiography revealed no dilatation during the clinical course, and there was no inflammatory changes or abnormal intimal thickening at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)
Scintigraphic Thyroid Abnormalities after Radiation
Authors: CLlCERlO GONZALEZ-VILLALPANDO
Journal: Annals of Internal Medicine (1982)

We did 99mTc-pertechnetate thyroid scintigraphy on 99 subjects with no history of therapeutic irradiation to the head or neck. They were compared with 198 irradiated patients selected from a group of over 1700 who were evaluated because of radiation treatment for benign head and neck conditions during childhood. The two groups were similar with respect to age and sex distribution. There were significantly more abnormal scintigrams in the irradiated group (55 of 198 patients versus one of 99 controls). Even after patients and controls with palpable nodules were excluded from the analysis there were still more abnormal scintigrams in the irradiated group (16 of 150 irradiated versus one of 97 control subjects). We conclude that thyroid nodules, including the smaller, nonpalpable nodules discovered by scintigraphy, are related to previous radiation therapy. For persons at substantial risk, such as those who received high-dose treatment (greater than 700 R) during childhood, the data support the use of screening scintigraphy, even with normal findings on palpation.
ACUTE DERMATITIS FROM THE WEARING OF "HORN-RIM" SPECTACLES
Authors: Irwin C. Sutton
Journal: JAMA (1927)

Every dermatologist has seen actual burns from celluloid, for children's toys, combs and toilet articles are notoriously inflammable and almost explosive in nature. The case reported here is the first definite instance I have ever seen of an acute, inflammatory dermatitis produced from the wearing of spectacles. The patient was seen through the courtesy of Dr. Orrie E. Ghrist of Glendale, Calif., who first suspected the cause of the trouble. <h3>REPORT OF CASE</h3><h3>History.</h3> —Mrs. M. S. V., a widow, aged 57, complained of a burning eruption of the face. Three days before examination, she had worn a new pair of spectacles for only half an hour, while glancing over the evening paper. On retiring she felt a severe burning about the face and on arising was frightened to find that her eyes were swollen shut. <h3>Examination.</h3> —The patient was well nourished. There was
Toxocariasis and eosinophilic meningitis.
Authors: I M Gould, S Newell, S H Green, R H George
Journal: BMJ (1985)

Une observation tres rare chez une malade de 11 ans: meningite a eosinophiles due a une infection par Toxocara canis. L'enfant ne presente pas de pica, mais des chiots presents dans l'entourage sont la source des parasites. Traitement efficace par diethylcarbamazine pendant 10 j
Predictors of disability in a longitudinal sample of patients with rheumatoid arthritis.
Authors: J P Leigh, J F Fries
Journal: Annals of the Rheumatic Diseases (1992)

Information from the Health Assessment Questionnaire (HAQ) is used to identify which variables measured in 1981 successfully predict the severity of disease in 1989 and the eight year change in severity of disease in a sample of 330 residents of Santa Clara County, California, USA. This study is exploratory and no previous hypotheses are made. Using univariate correlations and stepwise linear regressions, initial values of a number of variables are found to be useful predictors including, in order: the HAQ disability index, pain scale, global health status, tender joints, few work hours, age, female sex, never married, widowhood, and occupation as operative (e.g. dry wall installers, assemblers). Data suggest that deterioration over eight years is least rapid for those with severe disease in 1981. A mathematical identity suggests that analyses of the changes in severity versus analyses of 1989 severity are identical, provided that the 1981 disability index is entered as a covariate. The initial level of the disability index of the HAQ is by far the strongest predictive variable and provides a clinically important gauge for the likelihood of future impairment.
RETRACTED: Physical and Functional Interaction of DNA Methyltransferase 3A with Mbd3 and Brg1 in Mouse Lymphosarcoma Cells
Authors: Jhrana Datta, Sarmila Majumder, Shoumei Bai, Kalpana Ghoshal, Huban Kutay, David Spencer Smith, John W. Crabb, Samson T. Jacob
Journal: Cancer Research (2005)

Dnmt3a and Dnmt3b are de novo DNA methyltransferases that also act as transcriptional repressors independent of methyltransferase activity. To elucidate the underlying mechanism of transcriptional repression, Dnmt3a was purified from mouse lymphosarcoma cells (P1798) by extensive fractionation on five different chromatographic matrices followed by glycerol density gradient centrifugation. Liquid chromatography electrospray tandem mass spectrometry analysis of Dnmt3a-associated polypeptides identified the methyl CpG binding protein Mbd3, histone deacetylase 1(Hdac1), and components of Brg1 complex (Brg1, Baf155, and Baf57) in the purified preparation. Association of Dnmt3a with Mbd3 and Brg1 was confirmed by coimmunoprecipitation and coimmunolocalization studies. Glutathione S-transferase pulldown assay showed that the NH2-terminal ATRX homology domain of Dnmt3a interacts with the methyl CpG binding domain of Mbd3 and with both bromo and ATPase domains of Brg1. Chromatin immunoprecipitation assay revealed that all three proteins are associated with transcriptionally silent methylated metallothionein (MT-I) promoter in the mouse lymphosarcoma cells. To understand the functional significance of their association with the promoter, their role on the MT-I promoter activity was analyzed by transient transfection assay. The results showed that Mbd3 and Dnmt3a specifically inhibited the methylated promoter, and the catalytic activity of Dnmt3a was dispensable for the suppression. In contrast, the wild-type but not the ATPase-inactive mutant of Brg1 suppressed MT-I promoter irrespective of its methylation status, implicating involvement of ATP-dependent chromatin remodeling in the process. Coexpression of two of the three interacting proteins at a time augmented their repressor function. This study shows physical and functional interaction of Dnmt3a with components of nucleosome remodeling machinery.
Cyclic Adenosine Monophosphate as a Mediator of Hormone Action
Authors: Grant W. Liddle, Joel G. Hardman
Journal: New England Journal of Medicine (1971)

ACCORDING to the classic definition, hormones are substances that are secreted by certain tissues and are carried by the circulation to other tissues, where their metabolic effects appear. Only in very recent years has progress been made in understanding how hormones exert their metabolic effects on target tissues. It is now clear that one mechanism through which a hormone can act is to stimulate the formation of cyclic adenosine monophosphate (AMP) within a target cell; cyclic AMP then acts within the cell to carry out the metabolic work familiarly attributed to the hormone.Discovery of Cyclic AMPIn the 1940's . . .
Mapping of vascular dendritic cells in atherosclerotic arteries suggests their involvement in local immune-inflammatory reactions
Authors: Y Bobryshev
Journal: Cardiovascular Research (1998)

We previously demonstrated that vascular dendritic cells (VDCs) are present in the intima of large arteries and that their numbers are increased in atherosclerotic lesions. This study was undertaken to determine whether VDCs are involved in immune-mediated reactions in atherogenesis.Specimens of carotid artery and aorta were obtained at operation. VDCs were identified with anti-CD1a or with S-100. Co-localisation of VDCs with different intimal cells, including T-cells and macrophages, was studied using a double immunostaining procedure. In areas where the co-localising cells were detected, the peculiarities of expression of HLA-DR, ICAM-1, VCAM-1 were examined.In all the atherosclerotic plaques, VDCs were seen in contact with T-cells, but these co-localising cells were irregularly distributed and were mainly found in zones of neovascularisation containing inflammatory infiltrates. In other areas, T-cell/VDC co-localisation was rarely detected but VDCs were often found in contact with macrophages. VDCs were detected also in the media beneath atherosclerotic lesions and in the adventitia, where they were mostly around vasa vasorum, especially in areas exhibiting signs of acute inflammation. In these areas VDCs expressed ICAM-1, VCAM-1 and were in contact with T-cells. In both plaques and in the adventitia, the areas with co-localising VDCs and T-cells corresponded to the areas with HLA-DR expression.The results suggest that VDCs are involved in T-cell activation in atherogenesis. There are two regions within the arterial wall where VDC/T-cell co-localisation mostly occurs, namely, in zones of neovascularisation containing inflammatory infiltrates located within atherosclerotic lesions, and in areas with inflammatory infiltrates around vasa vasorum in the adventitia. Possibly, some intimal VDCs migrate through the media and adventitia to adjacent lymph nodes where they present atherosclerosis associated antigens. We also speculate that VDC/macrophage contacts are essential in processing immune information in atherogenesis.
Heterozygote Detection in Cystinosis, Using Leukocytes Exposed to Cystine Dimethyl Ester
Authors: Reuben Steinherz, Frank Tietze, Timothy Triche, Andrea Modesti, William A. Gahl, Joseph D. Schulman
Journal: New England Journal of Medicine (1982)

CYSTINOSIS, a genetic disorder characterized by autosomal recessive inheritance, typically produces progressive renal disease and death during childhood.1 , 2 Many cystinotic tissues, including isolated leukocytes3 and cultured fibroblasts,4 have large increases in intracellular cystine content found primarily within the lysosomes.5 , 6 Heterozygotes for cystinosis have no crystalline deposits in any tissues.1 , 2 In groups of heterozygotes, a small mean increase in intracellular cystine content can be found in isolated leukocytes and cultured skin fibroblasts,3 , 4 but some obligate heterozygotes cannot be identified since their fibroblast or leukocyte cystine concentrations are within the normal range.1 2 3 4 Subcellular fractionation studies7 or selective vacuolation with cysteine-penicillamine disulfide8 have . . .
Refractory Osteomalacia: Factors in Pathogenesis and Treatment.
Authors: B. Frame
Journal: Annals of Internal Medicine (1962)

s1 April 1962Refractory Osteomalacia: Factors in Pathogenesis and Treatment.B. Frame, M.D., F.A.C.P., R. W. Smith Jr., M.D., F.A.C.P., J. L. Fleming, M.D., G. Manson, M.D.B. Frame, M.D., F.A.C.P.Search for more papers by this author, R. W. Smith Jr., M.D., F.A.C.P.Search for more papers by this author, J. L. Fleming, M.D.Search for more papers by this author, G. Manson, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-674_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptVarieties of rickets and osteomalacia that are resistant to treatment with large doses of vitamin D have recently received increasing medical attention. The etiologic role for primary vitamin D resistance versus a primary renal tubular defect for phosphorus in the condition has not as yet been fully defined.The authors have under observation three cases of congenital and two cases of acquired refractory rickets and osteomalacia. Metabolic features include persistent fasting hypophosphatemia, increased renal clearance of phosphorus, decreased intestinal absorption of calcium, and failure to respond to conventional doses of vitamin D. The more common forms of rickets and osteomalacia... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Detroit, Mich. (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAcquired nonfamilial osteomalaciaThe treatment of adult phosphate diabetes and Fanconi syndrome with neutral sodium phosphate 1 April 1962Volume 56, Issue 4Page: 674-675KeywordsCalciumPathogenesisPhosphorusVitamin D Issue Published: 1 April 1962 PDF downloadLoading ...
PUBLIC MEDICAL CARE IN NEW YORK STATE
Authors: THOMAS PARRAN
Journal: JAMA (1933)

To what extent does the state now assume responsibility for the medical care of its citizens? In this paper I attempt to answer the question through an analysis of existing laws and current practices in the state of New York. Through a succession of far-reaching laws for human welfare, the state and local governments in New York already have become responsible for many and diverse types of medical care, supplementing traditional preventive health functions. The treatment of mental disease, for example, has been a state function since 1890. There has been built up an excellent system of hospitals, with a patient population of nearly 55,000, maintained at a cost of about $20,000,000 a year. Appearing frequently in old laws was the term "pauper insane," a term which now is replaced by "persons with mental disease." This well illustrates the change in public concept toward this problem. Supplementing the excellent system
Pro-Substance P for Evaluation of Risk in Acute Myocardial Infarction
Authors: Leong L. Ng, Jatinderpal K. Sandhu, Hafid Narayan, Paulene A. Quinn, Iain B. Squire, Joan E. Davies, Joachim Struck, Andreas Bergmann, Alan Maisel, Donald J.L. Jones
Journal: Journal of the American College of Cardiology (2014)
Clinical Aspects of Commercial Aviation Medicine
Authors: George J. Kidera
Journal: JAMA (1967)

Growth and progress have become so commonplace in recent times that various language devices are being used to give these concepts extra intensity. To indicate really significant progress, for example, we now say that a "breakthrough" has occurred. And to express the idea of sizable increases, we resort to the word "explosion," as in population explosion, cultural explosion, wage explosion, and suburban explosion. The growth of air transportation in the last several years is among such detonations. Since 1962, the average annual growth rate of the US scheduled airlines has been about 16%, which is considerably higher than for any other major industry. And the outlook for further increases is very favorable. The Air Transport Association predicts that by 1975 the nation's airlines of all types, including international carriers, will fly 336 million passengers yearly, as compared with 97 million in 1965. Last year United Air Lines carried 18,040,000 passengers,