tbuckley/cabot-search huggingface dataset:
Phenotype-Genotype Correlations in a Series of Wolfram Syndrome Families
Authors: Casey J.A. Smith, Patricia A. Crock, Bruce R. King, Cliff J. Meldrum, Rodney J. Scott
Journal: Diabetes Care (2004)

OBJECTIVE—Wolfram syndrome is an extremely rare autosomal-recessive disorder that predisposes the development of type 1 diabetes in association with progressive optic atrophy. The genetic basis of this disease has been shown to be due to mutations in the WFS1 gene. The WFS1 gene encodes a novel transmembrane protein called wolframin, which recent evidence suggests may serve as a novel endoplasmic reticulum calcium channel in pancreatic β-cells and neurons. Genotype-phenotype correlations in this syndrome are becoming apparent and may help in explaining some of the variable characteristics observed in this disease. RESEARCH DESIGN AND METHODS—In this report, we have studied 13 patients with Wolfram syndrome from nine families to further define the relationship between mutation site and type with specific disease characteristics. RESULTS—A severe phenotype was seen in patients with mutations in exon 4 and with a large deletion encompassing most of exon 8. In total, nine novel mutations were identified as well as three new silent polymorphisms. CONCLUSIONS—Similar to all other mutation reports, most causative changes identified in the WFS1 gene occurred in exon 8, and only one was identified outside this region in exon 4.
TCTAP A-097 Prevalence of Coronary Artery Disease in Critical Limb Ischemia Patients Undergoing Endovascular Therapy in Asian Population
Authors: Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Yoonjee Park, Akkala Raghavender Goud, Hu Li, Sunki Lee, Ji Bak Kim, Sung Il Im, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2014)
Polymorphisms in the chemokine (C-X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 epression in monocyte-derived dendritic cells
Authors: Markus Mezger, Michael Steffens, Melanie Beyer, Carolin Manger, Johannes Eberle, Mohammad-Reza Toliat, Thomas F. Wienker, Per Ljungman, Holger Hebart, Hans Jürgen Dornbusch, Hermann Einsele, Juergen Loeffler
Journal: Blood (2007)
Psychological Features of Acromegaly
Authors: Keli Furman, Shereen Ezzat
Journal: Psychotherapy and Psychosomatics (1998)

Acromegaly is a serious but often undiagnosed condition that is often unrecognized for many years. The delay from onset of symptoms until the time of diagnosis results in a unique constellation of physical and mental problems for patients and health care professionals. The purpose of this chapter is to identify the psychological consequences experienced by individuals affected with pituitary tumors which alter growth hormone release. As little research has been completed on the subject, very little is known, or has been applied, in the treatment of these patients. To identify the presence of psychological features, the research which exists and an in-depth qualitative analysis of the personal experience of one of the authors (K.F.), having suffered a pituitary macroadenoma with accompanying acromegaly, is described. Our findings are compared with those from an earlier series and the few published reports.
The Proposed Government Health Insurance Company — No Substitute for Real Reform
Authors: Victor R. Fuchs
Journal: New England Journal of Medicine (2009)

As pressure builds on the White House and Congress to deliver on their promise of health care reform, the idea of a government health insurance company to compete with for-profit and not-for-profit private companies is gaining political momentum. Advocates claim that this new company would be more efficient, honest, and successful in forcing lower reimbursement rates on physicians and hospitals.1 However, a close look at how the present health care system functions, what its major problems are, and what reforms are needed to solve them suggests that this new idea is not the answer. The three major problems of the . . .
Tissue factor–positive neutrophils bind to injured endothelial wall and initiate thrombus formation
Authors: Roxane Darbousset, Grace M. Thomas, Soraya Mezouar, Corinne Frère, Rénaté Bonier, Nigel Mackman, Thomas Renné, Françoise Dignat-George, Christophe Dubois, Laurence Panicot-Dubois
Journal: Blood (2012)
Studies of the absorption and removal of propranolol in hypertensive patients during therapy.
Authors: C A Chidsey, P Morselli, G Bianchetti, A Morganti, G Leonetti, A Zanchetti
Journal: Circulation (1975)

The variability of plasma propranolol concentrations has been determined in a large group of patients being treated with the drug. Although the average patient achieved a therapeutic plasma level with 160 mg/day, there was marked interpatient variation. This was found to be primarily the result of differences in effective absorption of the drug, which averaged 46% of the oral dose but ranged from 20 to 80%. Propranolol disappeared from plasma with a half-life of 4.7 hours and its removal appeared to follow dose independent kinetics with no evidence of saturation of hepatic metabolism. The derived pharmacokinetic values of volume of distribution and clearance rate have been used to provide guidelines for initiating propranolol therapy intravenously, and the schedule of 8 mg as a loading dose and 0.02 mg/min as a sustaining dose has been suggested.
Antiangiogenic Therapy Decreases Integrin Expression in Normalized Tumor Blood Vessels
Authors: Virginia J. Yao, Michael G. Ozawa, Amanda S. Varner, Ian M. Kasman, Yvan H. Chanthery, Renata Pasqualini, Wadih Arap, Donald M. McDonald
Journal: Cancer Research (2006)

Abstract Tumor blood vessels normalized by antiangiogenic therapy may provide improved delivery of chemotherapeutic agents during a window of time but it is unknown how protein expression in tumor vascular endothelial cells changes. We evaluated the distribution of RGD-4C phage, which binds αvβ3, αvβ5, and α5β1 integrins on tumor blood vessels before and after antiangiogenic therapy. Unlike the control phage, fd-tet, RGD-4C phage homed to vascular endothelial cells in spontaneous tumors in RIP-Tag2 transgenic mice in a dose-dependent fashion. The distribution of phage was similar to αvβ3 and α5β1 integrin expression. Blood vessels that survived treatment with AG-013736, a small molecule inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors, had only 4% as much binding of RGD-4C phage compared with vessels in untreated tumors. Cellular distribution of RGD-4C phage in surviving tumor vessels matched the α5β1 integrin expression. The reduction in integrin expression on tumor vessels after antiangiogenic therapy raises the possibility that integrin-targeted delivery of diagnostics or therapeutics may be compromised. Efficacious delivery of drugs may benefit from identification by in vivo phage display of targeting peptides that bind to tumor blood vessels normalized by antiangiogenic agents. (Cancer Res 2006; 66(5): 2639-49)
Repair of Tetralogy of Fallot in Neonates and Young Infants
Authors: F. A. Pigula, P. N. Khalil, J. E. Mayer, P. J. del Nido, R. A. Jonas
Journal: Circulation (1999)

The timing of repair of tetralogy of Fallot (TOF) remains controversial. Advantages to early complete repair include removal of right ventricular outflow tract obstruction, alleviation of systemic hypoxia, and avoidance of palliation with an arteriopulmonary shunt.This is a retrospective review of 99 children with TOF pulmonary stenosis (TOF/PS) or TOF pulmonary atresia (TOF/PA) who were <90 days of age undergoing early complete repair. Fifty-nine were prostaglandin E dependent, and 91% of neonates were symptomatic at the time of repair. Univariate and multivariate analyses of patient characteristics, anatomic features, and operative management showed the diagnosis of TOF/PA and smaller body surface area to be the only independent risk factors for death. Early mortality was 3% (3 of 99), and actuarial survival rates were 94% at 1 year and 91.6% at 5 years. Freedom from catheterization was 86% at 1 year and 73% at 5 years. Patients repaired for TOF/PA had a significantly lower freedom from reoperation than did those repaired for TOF/PS.Early complete TOF repair can be accomplished with a low mortality. Children with TOF/PA repaired had a lower freedom from reoperation that did those with TOF/PS. Longer follow-up, with emphasis on arrhythmias and right ventricular function, is required to define the long-term benefits of early repair.
Does the Metabolic Syndrome Exist?
Authors: Scott M. Grundy
Journal: Diabetes Care (2006)

Response to GrundyA key question in the debate concerning the metabolic syndrome (1,2) is whether the risk accompanying it is more than the sum of its parts.Grundy (1) asserts that "risk factors are multiplicative, i.e., risk for ASCVD [atherosclerotic cardiovascular disease] from risk factors rises geometrically, not linearly, as the number of risk factors increases.Therefore, total risk is more than a summation of the individual factors."The study by Yusuf et al. ( 3) is offered to support this statement, but this study is a standardized case-control study of 27,098 participants in 52 countries representing several major ethnic groups to assess the relation between BMI, waist and hip circumferences, and waist-to-hip ratio to myocardial infarction overall and for each group.The metabolic syndrome is not even mentioned in the article.In the same issue of Diabetes Care, Sunderstro ¨m et al. ( 4) published a study evaluating the risk factors for cardiovascular death in Ͼ2,000 individuals followed for 30 years after being studied at age 50.More than 1,000 of them were reexamined at age 70 and followed for 9 more years.Sunderstro ¨m et al. showed that the "metabolic syndrome did not predict cardiovascular mortality independently of its individual components at any age" and concluded that "the metabolic syndrome might be viewed as a clinically handy summary measure of nontraditional risk factors rather than as a strong biological entity."Thus, this evidence suggests that the answer to the key question posed above is that the risk of the metabolic syndrome for cardiovascular events is no more than the sum of its parts.Whether the metabolic syndrome serves an important function to alert physicians and patients of the importance of addressing these risk factors is a separate issue.
Hapten-specific T-cell lines in guinea-pig contact sensitivity: carrier specificity and specific accumulation
Authors: L. POLAK, R. J. SCHEPER
Journal: British Journal of Dermatology (1985)

Dinitrophenyl‐specific T‐cell lines were established by culturing lymph node‐derived lymphocytes from dinitrochlorobenzene‐sensitized guinea‐pigs with dinitrophenyl‐modified macro‐phages. Cells from this line were all Ia‐positive and formed E‐rosettes with rabbit erythrocytes; no Ig‐positive cells were present in this suspension. Expanded cells exhibited enhanced in vitro and in vivo activity as demonstrated by DNA synthesis and systemic adoptive transfer of contact sensitivity. In vitro DNA synthesis was elicited not only by specific hapten‐modified macrophages but also by conjugates of the hapten with homologous (GPA) and even heterologous (BGG, HSA) proteins, thus demonstrating the loss of carrier specificity. Moreover, the proliferative response of expanded cells was elicited not only with hapten‐modified syngeneic (strain 2) but also with allogeneic (strain 13) macrophages. Cells from hapten‐modified T‐cell lines, but not from lymph nodes from in vivo primed guinea‐pigs, showed specific accumulation in contact sensitivity skin test sites. Attempts to establish hapten‐specific T‐cell clones were also at least partially successful.
Toxic Shock Syndrome: Back to the Future
Authors: Bruce B. Dan
Journal: JAMA (1987)

In words that would transmit the heart-sinking fear of the contagion across 24 centuries, Thucydides dutifully chronicled the clinical features of the plague of Athens. The horrifying epidemic would not only kill tens of thousands of soldiers and civilians, it would alter the course of the Peloponnesian War, and change history. Although the awful spectacle was depicted as "men dying like sheep,"<sup>1</sup>the pestilence was notable for far more than just its numerical devastation. It was a bewildering constellation of signs and symptoms that no physician or historian had ever recorded before. Its victims, previously in good health, were suddenly stricken with high fever, sneezing, coughing, and hoarseness. They rapidly developed nausea, vomiting, and diarrhea, with a puzzling combination of conjunctival and oropharyngeal hyperemia and erythroderma. So unbearable was their fever that many of the sick plunged themselves into cooling water to relieve their "agonies of unquenchable thirst." Despite
Symptom Formation Reconsidered in Psychosomatic Terms
Authors: Philip Pinkerton
Journal: Psychotherapy and Psychosomatics (1974)

A classifying system is presented for interpreting physical symptoms in childhood disorder under three main headings. The first of these is the somatopsychic sequence in which the basic substrate is an organic lesion giving rise secondarily to intellectual and emotional repercussions. The second pattern is the pseudosomatic sequence in which the symptom presentation, though physical, has a basis of purely emotional pathology. The third pattern is the psychosomatic sequence which, it is suggested, should be retained for those specific disorders like asthma, eczema, migraine and spastic colon, which have a pathophysiological substrate activated by emotional factors, so that the resulting disorder has a conjoint aetiology. The principle common to all three syndromes is that symptom formation is dependent first upon the lesion itself (its nature, duration and severity); secondly, upon the child's attitude to it; and finally, upon the parental attitude to it.
Dentist's occupational asthma, rhinoconjunctivitis, and allergic contact dermatitis from methacrylates
Authors: M. Lindström, K. Alanko, H. Keskinen, L. Kanerva
Journal: Allergy (2002)

Background: Allergic contact dermatitis (ACD) caused by (meth)acrylates (MA) is common in dental personnel. MAs have also caused asthma and rhinoconjunctivitis, but asthma, rhinoconjunctivitis and ACD caused by MAs in the same patient appears to be very rare. Methods: Occupational asthma and rhinoconjunctivitis were diagnosed in a dentist according to patient history, PEF monitoring, and a work‐simulated bronchial provocation test. ACD was diagnosed by skin‐patch testing with MAs with the occlusive Finn Chamber‐technique. Results: The patient's skin‐prick test reactions to common environmental allergens and MAs were negative. The total IgE was not elevated. Occupational asthma was diagnosed by a specific inhalation challenge test in which the patient handled liquid dental MAs for 30 min causing a delayed 23% reduction in FEV1. The provocation test also resulted in rhinoconjunctivitis. On patch testing, positive reactions were provoked by several MAs including 2‐hydroxyethyl methacrylate (2‐HEMA) to which the patient was occupationally exposed. The patient has not been able to continue her work with dental MAs. Conclusions: A case of occupational asthma, rhinoconjunctivitis and ACD caused by dental acrylate compounds is presented. Patients with respiratory hypersensitivity from MAs have to stop working with MAs, whereas patients with ACD from MAs need to avoid direct contact with MAs, but can often continue in their present job if they use no‐touch techniques.
Lipid Adjustment in the Analysis of Environmental Contaminants and Human Health Risks
Authors: Enrique F. Schisterman, Brian W. Whitcomb, Germaine M. Buck Louis, Thomas A. Louis
Journal: Environmental Health Perspectives (2005)

The literature on exposure to lipophilic agents such as polychlorinated biphenyls (PCBs) is conflicting, posing challenges for the interpretation of potential human health risks. Laboratory variation in quantifying PCBs may account for some of the conflicting study results. For example, for quantification purposes, blood is often used as a proxy for adipose tissue, which makes it necessary to model serum lipids when assessing health risks of PCBs. Using a simulation study, we evaluated four statistical models (unadjusted, standardized, adjusted, and two-stage) for the analysis of PCB exposure, serum lipids, and health outcome risk (breast cancer). We applied eight candidate true causal scenarios, depicted by directed acyclic graphs, to illustrate the ramifications of misspecification of underlying assumptions when interpreting results. Statistical models that deviated from underlying causal assumptions generated biased results. Lipid standardization, or the division of serum concentrations by serum lipids, was observed to be highly prone to bias. We conclude that investigators must consider biology, biologic medium (e.g., nonfasting blood samples), laboratory measurement, and other underlying modeling assumptions when devising a statistical plan for assessing health outcomes in relation to environmental exposures.
Criteria in the Choice of a Computer System
Authors: Samuel Raymond
Journal: JAMA (1974)

IN general, the computer contributes to improved patient care in the clinical laboratory principally through improvement in laboratory and medical records. It helps to provide complete and accurately verified input.<sup>1</sup>It has the capacity to collate reliably, to print legibly, and to retrieve records rapidly. All these are important improvements over handwritten records. When combined with a useable system of useful laboratory reports, these functions of the computer can afford an improvement in the clerical tasks of patient care analogous to the improvement in the intellectual sphere provided by Lawrence Weed's system of problem-oriented records. On the other hand, the almost infinite powers of the computer in clerical tasks have led to the concept of having the computer record everything in the expectation that it will somehow sort out all of the data and give us back just what we need. I suggest that Dr. Weed has done more
CD28 signals through acidic sphingomyelinase.
Authors: L M Boucher, K Wiegmann, A Fütterer, K Pfeffer, T Machleidt, S Schütze, T W Mak, M Krönke
Journal: The Journal of Experimental Medicine (1995)

T cell receptor recognition of antigen can lead either to T lymphocyte differentiation and proliferation or to a state of unresponsiveness, which is dependent on whether appropriate costimulatory signals are provided to the mature T cell. We have investigated a novel intracellular signaling pathway provided by the costimulatory molecule CD28. CD28 engagement triggers the activation of an acidic sphingomyelinase (A-SMase), which results in the generation of ceramide, an important lipid messenger intermediate. A-SMase activation by CD28 occurred in resting as well as in activated primary T cells or leukemic Jurkat cells. In contrast, ligation of either CD3 or CD2 did not result in A-SMase activation. Overexpression of recombinant A-SMase in Jurkat T cells substituted for CD28 with regard to nuclear factor-kB activation. These data suggest that CD28 provides an important costimulatory signal by activation of an acidic sphingomyelinase pathway.
Abnormal Gallium Scan Patterns of the Salivary Gland in Pulmonary Sarcoidosis
Authors: FRED S. MISHKIN
Journal: Annals of Internal Medicine (1978)

Brief Reports1 December 1978Abnormal Gallium Scan Patterns of the Salivary Gland in Pulmonary SarcoidosisFRED S. MISHKIN, M.D., TOSHIYUKI T. TANAKA, M.D., ALBERT H. NIDEN, M.D., Martin Luther King Jr.FRED S. MISHKIN, M.D.Search for more papers by this author, TOSHIYUKI T. TANAKA, M.D.Search for more papers by this author, ALBERT H. NIDEN, M.D.Search for more papers by this author, Martin Luther King Jr.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-89-6-933 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSalivary gland abnormalities in sarcoidosis are thought to be unusual, a conclusion based on lack of symptoms. Recently, however, more thorough investigations by means of biopsy or objective tests of exocrine function such as quantitative salivary juice collection and enzyme analysis have suggested that salivary gland involvement may be much more prevalent (1, 2). We have had the opportunity to assess salivary gland scans from a group of 40 patients, all with histologic evidence of granulomatous involvement of the lung and a clinical course consistent with sarcoidosis. We report our finding here.We performed gallium citrate whole body scans...References1. TURIAFBATTESTI JJ: Gougerot-Sjögren syndrome and sarcoidosis. Ann NY Acad Sci 278:401-405, 1976 CrossrefMedlineGoogle Scholar2. BHOOLAMCNICOLOLIVERFORAN KMSJ: Changes in salivary enzymes in patients with sarcoidosis. N Engl J Med 281:877-879, 1969 CrossrefMedlineGoogle Scholar3. NIDENMISHKINKHURANA AFM: 67Gallium citrate lung scans in interstitial lung disease. Chest 69(suppl):266-268, 1976 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: General Hospital Los Angeles, California PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByLack of Increased FDG Uptake in the Lacrimal and Salivary Glands in Patients With Sarcoidosis and Potential Underlying MechanismSarcoidosisNUCLEAR IMAGINGSpecificity and Sensitivity of Distinctive Chest Radiographic and/or 67Ga Images in the Noninvasive Diagnosis of SarcoidosisPlain radiography and sialographyThoracic imaging with 67galliumThe role of gallium-67 in the clinical evaluation of sarcoidosisSarcoidosis of the parotid salivary glandsThe role of nuclear scanning in head and neck surgeryGallium-67 in the evaluation of sarcoidosis: correlations with serum angiotensin-converting enzyme and bronchoalveolar lavage.Radionuclide salivary gland imagingDiseases of Obscure Etiology: Sarcoidosis, Wegener’s Granulomatosis, and Midline Granuloma 1 December 1978Volume 89, Issue 6Page: 933-935KeywordsBiopsyEnzymesGallium scanLungsQuantitative analysisSalivary glandsSarcoidosis Issue Published: 1 December 1978 PDF DownloadLoading ...