tbuckley/cabot-search huggingface dataset:
Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver: Identification of a human hepatic progenitor cell?
Authors: Ulrich Baumann, Heather A. Crosby, Pramila Ramani, Deirdre A. Kelly, Alastair J. Strain
Journal: Hepatology (1999)

The stem cell factor (SCF)/c- kit ligand/receptor system has been implicated in stem (oval) cell activation following liver injury in the rat. The aim of this study was to determine the role of the SCF/c- kit system in pediatric human liver during acute and chronic liver injury. Tissue was obtained from hepatectomy specimens of patients undergoing liver transplantation for extrahepatic biliary atresia (EHBA) and fulminant hepatic failure (FHF). Specific expression of mRNA for c- kit and β-actin was measured by ribonuclease protection and by immunohistochemistry to localize c- kit in tissue sections. Expression of c- kit was detected at relatively consistent levels in normal and cirrhotic (EHBA) livers. However, in FHF, c- kit mRNA levels were elevated in 3 of 6 specimens. Immunolocalization highlighted the presence of small numbers of c- kit -positive cells in the portal tracts of normal livers with increased numbers in cirrhotic livers. The highest c- kit staining, however, was observed in FHF, in which, in addition to the cells in the portal tracts, discrete c- kit -positive cells were also found integrated into bile ducts. Colocalization studies demonstrated some of the c- kit -positive cells to be of mast cell, leukocyte, and hematopoietic cell origin. However, there remained a subset that was also negative for these markers. The up-regulation of c- kit receptor expression in diseased livers suggests an involvement of this receptor/ligand system in hepatic repair mechanisms, and we speculate that c- kit -positive cells may represent a hepatic progenitor cell population. The origin and growth/differentiation potential of these c- kit -positive cells is under investigation.
Heart failure with a normal ejection fraction
Authors: J. E Sanderson, G. W K Yip
Journal: BMJ (2009)

Is underdiagnosed, has a high mortality, and lacks evidence based treatment

The typical image of a patient with heart failure is of a breathless person with a large flabby heart, which contracts poorly with a reduced left ventricular ejection fraction. However, many patients, mainly elderly women, have symptoms of heart failure but their hearts are not enlarged. Echocardiography shows a relatively normal left ventricular ejection fraction but usually with some left ventricular hypertrophy. Because systolic function was thought to be normal or near normal, the term “diastolic heart failure” was coined for this group of patients. However, we now know that systolic function is not entirely normal, and the problem is not only caused by diastolic dysfunction; hence the term “heart failure with a normal ejection fraction” is more appropriate.

Recent epidemiological studies have shown that heart failure with a normal ejection fraction is now a more common cause of hospital admission than systolic heart failure in many parts of the world.1 2 Mortality is also similar for both types of heart failure.1 Yet recognition of heart failure with a normal ejection fraction is poor and few …
Early antibiotic treatment of reactive arthritis associated with enteric infections: clinical and serological study.
Authors: A Fryden, A Bengtsson, U Foberg, B Svenungsson, B Castor, A Karnell, R Schvarcz, B Lindblom, E Kihlstrom
Journal: BMJ (1990)

OBJECTIVE--To find out whether a 10-14 days9 course of antibiotics early in the course of reactive arthritis associated with enteric infections could reduce the severity and duration of the disease and whether the antibody response in patients with reactive arthritis associated with yersinia infection differed between those treated and those not treated with the antibiotics. DESIGN--Prospective multicentre trial in which patients were randomised to treatment or no treatment with antibiotics. Patients were seen at three and six weeks and three, six, nine, 12, and 18 months after their first visit. SETTING--Departments of infectious diseases in three hospitals in Linköping, Malmö, and Stockholm, Sweden. PATIENTS--40 Consecutive patients who had had symptoms of reactive arthritis associated with enteric infection for less than four weeks. INTERVENTIONS--20 Patients were allocated to treatment with antibiotics and 20 patients did not receive antibiotics. All patients received non-steroidal anti-inflammatory drugs, and four also received intra-articular steroid injections after at least six weeks9 observation. MAIN OUTCOME MEASURES--Arthritic symptoms assessed clinically and by using Ritchies9 index; blood measurements reflecting inflammatory activity; serum IgG, IgM, and IgA antibody titres; HLA tissue type. RESULTS--No difference was observed concerning duration of arthritis, grade of inflammation, and number of joints affected between patients treated and those not treated with antibiotics. Furthermore, there was no significant difference between the two groups in erythrocyte sedimentation rate and haptoglobin, IgG, and IgA concentrations. All values had returned to normal within three months. No patient developed chronic arthritis, but sustained slight arthralgia occurred in three patients. The HLA-B27 antigen was found in 23 (58%) of the patients, and its presence did not affect clinical outcome. The IgG, IgM, and IgA antibody responses were similar in patients treated with antibiotics and those not treated. CONCLUSION--Short term antibiotic treatment has no beneficial effect on the clinical outcome of reactive arthritis associated with enteric infection.
Genomics, Intellectual Disability, and Autism
Authors: Heather C. Mefford, Mark L. Batshaw, Eric P. Hoffman
Journal: New England Journal of Medicine (2012)

the age of 18 years, 1 affects 1.5 to 2% of the population in Western countries. 2 A diagnosis of intellectual disability is usually made when IQ testing reveals an IQ of less than 70, which means that often the diagnosis is not made until late childhood or early adulthood. However, most persons with intellectual disability are identified early in childhood on the basis of concern about developmental delays, which may include motor, cognitive, and speech delays. A genetic underpinning of this disorder has long been recognized in a subset of cases, with trisomy 21 (Down’s syndrome) detectable by chromosomal studies since 1959. 3 Trisomy 21 remains the most important chromosomal cause of intellectual disability. Single-gene causes have also been identified for a number of intellectual disability syndromes and include both autosomal and X-linked genes, with the fragile X syndrome being the most common of inherited syndromes caused by a single-gene defect leading to this phenotype in male patients. Autism spectrum disorders have been estimated to affect as many as 1 in 100 to 1 in 150 children. 4,5 Disorders on the autism spectrum share features of impaired social relationships, impaired language and communication, and repetitive behaviors or a narrow range of interests. Many children with autism spectrum disorders also have intellectual disability, and approximately 75% have lifelong disability requiring substantial social and educational support. Thus, autism and intellectual disability together represent an important health burden in the population and are frequent reasons for referral to genetics and developmental pediatrics clinics for a diagnostic workup. During the past decade, advances in genetic research have enabled genomewide discovery of chromosomal copy-number changes and single-nucleotide changes in patients with intellectual disability and autism as well as in those with other disorders. These technological advances — which include array comparative genomic hy bridization (CGH), single-nucleotide-polymorphism (SNP) genotyping arrays, and massively parallel sequencing — have transformed the approach to the identification of etiologic genes and genomic rearrangements in the research laboratory and are now being applied in the clinical diagnostic arena. Here we review these techniques and how they have enabled the rapid discovery of chromosomal and single-gene causes of intellectual disability and autism.
Proceed with caution: Peginterferon alpha-2a versus peginterferon alfa-2b in chronic hepatitis C. A systematic review of randomized trials
Authors: David Kershenobich, Linda Muñoz, René Malé, Jesús Gaytan, Francisco Sánchez
Journal: Hepatology (2010)

Two of the studies cited in Awad et al. (Sinha et al.4 and Kolakowska et al.5) were published as abstracts, without peer review. Three of the articles used a stratified randomization. Two of them (Ascione et al.6 and Rumi et al.7) used a stratified randomization by genotype, and in the study by McHutchison et al.8, randomization was stratified by level of HCV and race. Whereas most of the trials included treatment-naive patients, Laguno et al.9 worked with patients coinfected with human immunodeficiency virus and Scotto et al.10 included patients without response to previous treatment. McHutchison included different races, and although five trials included patients infected with genotype 1 to 4, two trials included patients with genotype 1 (McHutchison et al.8 and Yenice et al.11), and Kolakowska et al. included only patients with genotype 3. In the meta-analysis, 1016 patients with a lower dose of peginterferon alpha-2b were included. Simultaneously, Alavian et al.12 presented a very similar article: “The Comparative Efficacy and Safety of Peginterferon Alpha-2a vs. 2b for the Treatment of Chronic HCV Infection: A Meta-Analysis.” Alavian et al. analyzed only five of the eight trials used by Awad et al. Alavian et al. reach nearly the same conclusion, but at the same time stated “A longer duration of maximum serum concentration compared with PEG-IFN-α2b (168 versus 48-72 hours) yields greater SVR and higher neutropenia in PEG-IFN-α2a recipients.” Both authors1, 12 mentioned some awareness about the quality of the meta-analysis and the studies included in it. We think that conclusion must be interpreted both in light of the included trials and considering the effects of other factors, such as baseline HCV level, sex, race, and genotype. We strongly believe more research is needed before it is concluded one peginterferon is better than the other. David Kershenobich M.D., Ph.D.*, Linda Muñoz , René Malé , Jesús Gaytan§, Francisco Sánchez¶, * Laboratorio de Hígado, Páncreas y Motilidad, Departamento de Medicina Experimental, Facultad de Medicina de la UNAM, Hospital General de México, México DF, México, Unidad de Hígado, Departamento de Medicina Interna, Hospital Universitario “Dr. José E. González” Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México, Centro de Enfermedades Digestivas y Hepáticas SC, Instituto de Salud Digestiva y Hepáticas SC, Guadalajara, Jalisco, México, § Hospital de Infectología. Centro Médico Nacional “La Raza”. Instituto Mexicano del Seguro Social, México DF, México, ¶ Departamento de Gastroenterología. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,” México DF, México.
Induction of B cell apoptosis by TH0, but not TH2, CD4+ T cells.
Authors: X He, W Zhong, J J Goronzy, C M Weyand
Journal: Journal of Clinical Investigation (1995)

Engagement of the T cell receptor molecules with MHC-antigen complexes presented by B cells ascertains antigen specificity in T cell-dependent help. Ligation of MHC molecules on the surface of B cells, however, has not only been implicated in antigen-specific T-B cell interaction, but has also been linked to the induction of B cell apoptosis. To examine the role of T helper cells in either induction of immunoglobulin synthesis or B cell apoptotic death, we have facilitated T cell receptor-MHC interaction through a bacterial superantigen. CD4+ T cell clones could be categorized into two clearly distinct subsets based upon their ability to promote B cell help in the presence of superantigen. One subset of T cell clones supported immunoglobulin synthesis, and thus functioned as effective helper cells. B cells interacting with the second subset of T cells did not differentiate into antibody-secreting cells, but underwent apoptosis. Both types of helper cells were able to provide contact help after anti-CD3 stimulation. Induction of apoptosis was a dominant phenomenon; the addition of the superantigen suppressed immunoglobulin production in B cells activated by anti-CD3-stimulated helper T cells, indicating that the T cells delivered an apoptotic signal to the B cell. T cell clones providing effective MHC restrictive B cell help could be distinguished from T cells facilitating B cell apoptosis based on their lymphokine secretion profile. Induction of B cell apoptosis was a feature of T cells with a TH0 lymphokine pattern. Promotion of MHC-restricted B cell help was associated with a TH2 lymphokine profile. TH1-derived cytokines alone could not substitute for apoptosis-inducing T cells.
Adequacy of the Preclinical Safety Evaluation
Authors: Harold M. Peck
Journal: JAMA (1964)

THE SAFETY ASSESSMENT of a drug relates its usefulness for an intended purpose to its inherent manifestations of toxicity; any useful drug can be shown to cause some undesirable effects in man or animal if searched for adequately. Thus, following the election of a new compound for clinical trial, the pharmacologist undertakes to assess how useful it may be and the toxicologist determines how toxic it is for animals. The reconciliation of efficacy with toxicity determines the element of safety and on this basis a new and interesting chemical may merit clinical trial. How safe the drug is for general use in therapeutics requires a third factor of judgment: "For what purpose is it intended?" This decision frequently is a clinical one. If we accept the concept that a drug can produce toxic effects in animals if tested under experimental conditions that may be more rigorous than those employed in
Sulfonamide Hepatitis
Authors: James Fries, Reuben Siraganian
Journal: New England Journal of Medicine (1966)

AFTER fifteen years of widespread use of the soluble and longer-acting sulfonamides, particularly sulfisoxazole, without evidence of liver toxicity, reports of hepatic disease associated with these agents have appeared in recent months. Although extrapolation from experience with earlier sulfonamides suggested the possibility, no such association had previously been noted. The following case was due to sulfamethoxazole and sulfisoxazole.Case ReportA 60-year-old housewife was admitted to the hospital with jaundice. The family and past histories were negative for allergies and liver disease. Eight years previously a Urinary Tract infection had responded well to an unknown sulfonamide.One month before admission . . .
Megaloblastic Anemia in Sarcoidosis
Authors: M. C. SWEATMAN
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 January 1986Megaloblastic Anemia in SarcoidosisM. C. SWEATMAN, M.B., M.R.C.P., R. WILSON, M.B., M.R.C.P., D. N. MITCHELL, M.D., M.R.C.P.M. C. SWEATMAN, M.B., M.R.C.P.Search for more papers by this author, R. WILSON, M.B., M.R.C.P.Search for more papers by this author, D. N. MITCHELL, M.D., M.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-1-129_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We report the case of a patient with sarcoidosis and macrocytic anemia attributable to megaloblastic changes in a bone marrow infiltrated by typical sarcoid granulomas. Extensive investigation failed to reveal any other cause for her megaloblastic anemia.A 41-year-old white woman presented with lethargy, breathlessness, and weight loss. Physical findings included jaundice, bruising, ankle edema, and hepatosplenomegaly. Laboratory studies showed hemoglobin, 6.4 g/dL; erythrocyte count, 1.96 X 1012/L; mean cell volume, 101 fL; leukocyte count, 1.7 X 109/L; platelets, 87 X 109/L; and reticulocytes, 0.8%. A blood film showed macrocytosis, anisocytosis, poikilocytosis, and hypersegmented neutrophils. The clotting...References1. SCADDINGMITCHELL JD. Sarcoidosis. 2nd ed. London: Chapman and Hall Medical; 1985. CrossrefGoogle Scholar2. WEBBMITCHELLBRADSTREETSALSBURY ADCA. Splenomegaly and splenectomy in sarcoidosis. J Clin Pathol. 1979;32:1050-3. CrossrefMedlineGoogle Scholar3. TINKERVISWANATHANLAUFERMARGOLIS MBHI. Acute appendicitis and pernicious anemia as complications of gastrointestinal sarcoidosis. Am J Gastroenterol. 1984;79:868-72. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cardiothoracic Institute and Medical Research Council Tuberculosis and Chest Diseases Unit London SW3 6HP England PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1986Volume 104, Issue 1Page: 129-129KeywordsGranulomasHemoglobinHepatosplenomegalyMegaloblastic anemiaNeutrophilsPlateletsResearch laboratoriesReticulocytesSarcoidosisWeight loss Issue Published: 1 January 1986 PDF DownloadLoading ...
Shift system for senior house officer on call duties on a neonatal intensive care unit
Authors: A. Finn, B. D Speidel
Journal: BMJ (1988)

To reduce the number of hours that senior house officers in the neonatal department at Southmead Hospital, Bristol, have to work continuously a new on call rota was devised. The rota changed the traditional one in three system of 24 and 32 hour periods on call to one with two shifts each day, and it spread the workload more evenly among the personnel. The continuity of care of the patients was improved, no extra staff were recruited, and the new system was favoured by senior and junior medical and nursing staff.
Surgical Treatment of Ulcerative Colitis in Children
Authors: Kenneth C. Sawyer
Journal: JAMA (1960)

The course of medically intractable ulcerative colitis in children is discussed in the light of four cases which occurred in an 11-year-old boy and in three girls aged 9, 9, and 8 years. In pathology and clinical course the disease in children differed little from that in adults. In the fourth case symptoms persisted until the age of 18, when laparatomy revealed generalized abdominal carcinomatosis and was followed by death in three months. In the other three cases ileostomy, with more or less extensive colectomy, afforded dramatic relief; this was followed by a marked improvement in nutritional status and a gratifying degree of social development. The authors emphasize the excellent response to surgery in these medically intractable cases, the absence of physical or emotional disability attributable to the ileostomy, and the danger that carcinoma may appear in cases of ulcerative colitis of long standing.
Oral Calcium-loading Test in Infancy, with Particular Reference to Idiopathic Hypercalcaemia
Authors: D. G. D. Barr, J. O. Forfar
Journal: BMJ (1969)

An oral calcium-loading test suitable for infants is described and the usual response defined. In four acute cases of idiopathic hypercalcaemia a high and sustained rise in serum calcium occurred, suggestive of hyperabsorption and consistent with a vitamin-D-like effect. In four further infants with a milder illness suggestive of hypercalcaemia the fasting calcium levels were not grossly raised, but the test produced an exaggerated hypercalcaemic response. In this type of patient the test is more sensitive in the diagnosis of idiopathic hypercalcaemia than isolated measurements of serum calcium, especially if these are taken in the fasting state. Five patients on treatment and three whose treatment had been discontinued (but who subsequently relapsed or made a poor recovery) showed abnormal loading tests at a time when fasting calcium levels were normal. In two cases full recovery from the disease was associated with reversion of the test to normal. The test can therefore be used to indicate activity of the disease and consequently as a guide to therapy. In two cases a persistently abnormal loading test was associated with a poor long-term prognosis.
Predictors of Endotoxin Levels in U.S. Housing
Authors: Peter S. Thorne, Richard D. Cohn, Deepak Mav, Samuel J. Arbes, Darryl C. Zeldin
Journal: Environmental Health Perspectives (2008)

BackgroundThe relationship of domestic endotoxin exposure to allergy and asthma has been widely investigated. However, few studies have evaluated predictors of household endotoxin, and none have done so for multiple locations within homes and on a national scale.ObjectivesWe assayed 2,552 house dust samples in a nationwide study to understand the predictors of household endotoxin in bedroom floors, family room floors, beds, kitchen floors, and family room sofas.MethodsReservoir house dust from five locations within homes was assayed for endotoxin and demographic and housing information was assessed through questionnaire and onsite evaluation of 2,456 residents of 831 homes selected to represent national demographics. We performed repeated-measures analysis of variance (rANOVA) for 37 candidate variables to identify independent predictors of endotoxin. Meteorologic data were obtained for each primary sampling unit and tested as predictors of indoor endotoxin to determine if wetter or warmer microclimates were associated with higher endotoxin levels.ResultsWeighted geometric mean endotoxin concentration ranged from 18.7 to 80.5 endotoxin units (EU)/mg for the five sampling locations, and endotoxin load ranged from 4,160 to 19,500 EU/m2. Bivariate analyses and rANOVA demonstrated that major predictors of endotoxin concentration were sampling location in the home, census division, educational attainment, presence of children, current dog ownership, resident-described problems with cockroaches, food debris, cockroach stains, and evidence of smoking observed by field staff. Low household income entered the model if educational attainment was removed.ConclusionIncreased endotoxin in household reservoir dust is principally associated with poverty, people, pets, household cleanliness, and geography.
Mitogenic effect of lysosomal hydrolases on bovine tracheal myocytes in culture.
Authors: D B Lew, M C Rattazzi
Journal: Journal of Clinical Investigation (1991)

Studies were conducted to assess the mitogenic effect of lysosomal hydrolases, enzymes known to have an association with allergen- or ozone-induced airway hyperreactivity, on bovine tracheal myocytes in culture. Addition of purified human placental beta-hexosaminidase and partially purified bovine liver beta-glucuronidase resulted in the doubling of cell count after 4 d of incubation in medium M199 with 0.4% FBS. Unstimulated cells remained quiescent without a significant increase of cell count. Lysosomal hydrolases also selectively enhanced 3H-thymidine incorporation four to seven times more than that in vehicle-treated cells or cells treated with endotoxin, a common contaminant of purified enzymes. Ovalbumin (glycoprotein control), pronase, and lysozyme caused a modest but statistically insignificant increase (up to twofold) in 3H-thymidine incorporation. Elastase, collagenase and dialyzed E. coli beta-glucuronidase had no effect. The mitogenic effect of hydrolases was equally seen in quiescent, serum-depleted cells as well as in those maintained in medium with 10% FBS, suggesting that it was independent of serum factors. The effect of lysosomal hydrolases was inhibited by exposure to yeast mannan, and mannosylated human serum albumin had a mitogenic effect, suggesting the involvement of a mannose receptor. We conclude that lysosomal hydrolases may play a role in the development of the hyperplasia/hypertrophy of respiratory smooth muscle.