tbuckley/cabot-search huggingface dataset:
Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells
Authors: Jeffrey M. Milush, Kiran D. Mir, Vasudha Sundaravaradan, Shari N. Gordon, Jessica Engram, Christopher A. Cano, Jacqueline D. Reeves, Elizabeth Anton, Eduardo O’Neill, Eboneé Butler, Kathy Hancock, Kelly S. Cole, Jason M. Brenchley, James G. Else, Guido Silvestri, Donald L. Sodora
Journal: Journal of Clinical Investigation (2011)

SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4(+) T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3(+)CD4(-)CD8(-) T cells (double-negative T cells) partially compensates for CD4(+) T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4(+) T cells to SIV-negative animals resulted in rapid loss of CD4(+) T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4-low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4(+) T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4(+) T cell-like helper functions upon SIV-induced CD4(+) T cell depletion in this species.
Phenobarbital in the Monitoring of Compliance
Authors: MORGAN FEELY
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 July 1984Phenobarbital in the Monitoring of ComplianceMORGAN FEELY, M.D., M.R.C.P.I., DAVID PRICE, M.B., M.R.C.P., JONATHAN COOKE, M.PHARM.MORGAN FEELY, M.D., M.R.C.P.I.Search for more papers by this author, DAVID PRICE, M.B., M.R.C.P.Search for more papers by this author, JONATHAN COOKE, M.PHARM.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-101-1-138_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In their review, Eraker and associates (1) rightly point out that pharmacokinetic differences between drugs and patients have greatly limited the usefulness of measurements of (therapeutic) drug levels or pharmacologic markers in the assessment of compliance. We suggest that phenobarbital, a drug used extensively for more than 70 years, in the appropriate dosage, can serve as a widely applicable, quantitative indicator of compliance.Phenobarbital has a half-life of about 4 days in adults. Observations made during inpatient treatment (2) and in a prospective study that included monthly blood level monitoring (3) suggest that once age is taken...References1. ERAKER S, KIRSCHT J, and BECKER M. Understanding and improving patient compliance. Ann Intern Med. 1984;100:258-68. LinkGoogle Scholar2. SVENSMARK O and BUCHTHAL F. Diphenylhydantoin and phenobarbital: serum levels in children. Am J Dis Child. 1964;108:82-7. CrossrefMedlineGoogle Scholar3. FEELY M, O'CALLAGHAN M, DUGGAN B, and CALLAGHAN N. Phenobarbitone in previously untreated epilepsy. J Neurol Neurosurg Psychiatry. 1980;43:365-8. CrossrefMedlineGoogle Scholar4. PERUCCA E, RUPRAH M, RICHENS A, PARK B, BETTERIDGE D, and HEDGES A. Effect of low dose phenobarbitone on five indirect indices of hepatic microsomal enzyme induction and plasma lipoproteins in normal subjects. Br J Clin Pharmacol. 1981;12:529-96. CrossrefGoogle Scholar5. MATTSON R and CRAMER J. Phenobarbital: toxicity. In: WOODBURY DM, PENRY JK, PIPPINGER CE, eds. Antiepileptic Drugs. 2nd ed. New York: Raven Press; 1982:359. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MORGAN FEELY, M.D., M.R.C.P.I.; DAVID PRICE, M.B., M.R.C.P.; JONATHAN COOKE, M.PHARM.Affiliations: University of Leeds The General Infirmary Leeds LS1 3EX United Kingdom PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe effect of low-dose phenobarbitone on three indices of hepatic microsomal enzyme induction. 1 July 1984Volume 101, Issue 1Page: 138-139KeywordsBloodDrugsHalf lifeInpatientsPharmacokineticsProspective studiesTherapeutic drug monitoring ePublished: 1 December 2008 Issue Published: 1 July 1984 PDF downloadLoading ...
Trial evaluating overall survival in epithelial ovarian cancer (eoc) patients in second remission with an autologous dendritic cell therapy targeting mucin 1
Authors: Sharron Gargosky, Canvas Clinical Team
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Cvac is well tolerated with no serious adverse events related to Cvac treatment in CAN-003. Treatment with Cvac results in a mucin 1 specific T cell response. In the second remission patients the median PFS for Cvac was greater than 12.91 months versus a median PFS for SOC of 4.94
ON THE VARIATIONS OF THE PLASMA VITAMIN A LEVEL AFTER THE ADMINISTRATION OF LARGE DOSES OF VITAMIN A IN LIVER DISEASE 1
Authors: Hans Popper, Frederick Steigmann, Sol Zevin
Journal: Journal of Clinical Investigation (1943)

The vitamin A level of the blood temporarily rises after the ingestion of high doses of vitamin A. This rise, as shown in the usual tolerance curve, is modified in various clinical conditions, such as liver disease (1, 2).Two explanations have been presented for the flat tolerance curves found in liver disease.(1) The vitamin A stores in the liver regulate the shape of the curve, the increase being less marked with livers poor in vita- min A and, consequently, having high avidity for it (Ralli et al. ( 2)).In this case, the tolerance curve would represent a saturation curve.(2) Disturbed intestinal absorption leads to flat toler- ance curves (Breese and McCoord (1)).Ac- cording to this conception, the tolerance curve would represent an absorption curve.If toler- ance curves are saturation curves, they represent a clinical index of the hepatic vitamin A concen- tration, which in humans cannot be judged by the fasting blood level alone (3).If they are absorp- tion curves, they provide a means of studying de- ficiency of intestinal absorption.In this paper, the influence of the various liver diseases on vitamin A tolerance curves is studied.Furthermore, the attempt is made to answer the above questions regarding the significance of the tolerance curve and to explain its change in liver disease. MATERIAL AND METHODTolerance curves were performed on 108 patients.Of these, 71 were patients suffering from diseases of the livekor biliary tract.The remaining 37 cases were used for comparison.Patients with hernia or fracture served as hospital controls.Patients with uncomplicated peptic ulcer, gastric carcinoma, and pyloric obstruction were added for comparison, as examples of abdominal disease, and because, in most of these, liver biopsy specimens
Genetic Testing for Alzheimer Disease-Reply
Authors: Stephen G. Post, Peter J. Whitehouse
Journal: JAMA (1997)

<h3>In Reply.</h3> —We share Dr Tracy's hopes for a future in which preventive or delaying antidementia strategies are applied widely in asymptomatic individuals at higher risk for AD, which is a tremendous public health problem. However, although many exciting ideas exist about how to delay onset of AD, none are proven. Certainly prevention or a delay of onset are strategies increasingly within reach and of obvious moral and social value.<sup>1</sup>If some potentially AD-preventing compounds were to have adverse effects, then defining high-susceptibility subpopulations based on genetic testing would be laudable. But no link has yet been established between genotype (eg, the presence or absence of an<i>APOE</i>∈4 allele) and efficacy of potential therapies. From our focus group activities, it appears that many, if not most, caregivers would proceed with a susceptibility test only if preventive or delaying compounds are better established and much more clearly related to genotype than
Intraperitoneal Bleeding in a Patient with a Myelodysplastic Syndrome
Authors: HIROSHI NISHIYAMA, ALEXANDER G. FRANKL, G CHRISTOPHER RAUF
Journal: Clinical Nuclear Medicine (1987)

A patient with a bleeding diathesis secondary to myelo- dysplastic syndrome was studied with in vivo labeled red blood cells. There was persistent abnormal activity in the left upper quadrant and evanescent activity in the left side of the abdomen. The bleeding site was thought to be the stomach, but the gastric contents and stool were negative for blood. A paracentesis revealed hemoperitoneum and a laparotomy revealed active intraperitoneal bleeding from a ruptured spleen.
Nocturnal Angina Pectoris
Authors: H. J. Roberts
Journal: JAMA (1966)

To the Editor:—  I would suggest that myocardial glycopenia due to hypoglycemic attacks be seriously entertained. In studying scores of comparable challenging cases, I have demonstrated the presence of diabetogenic hyperinsulinism in the vast majority (Clin Res13:28, 1965). Occasionally, it could be convincingly documented only by the method of afternoon glucosetolerance testing (J Amer Geriatric Soc12:423, 1964) because of the cyclic intensification of insulinogenesis as the day advances. Major coronary artery stenosis or occlusion was not found in several such patients who experienced nocturnal exacerbations of typical angina pectoris, either by careful angiographic studies or direct examination at the time of surgery. The institution of a corrective diet aimed at preventing severe reactive hypoglycemia day and night promptly ameliorated and indefinitely prevented or minimized both nocturnal angina pectoris and associated abdominal or leg cramps in most of these patients, notwithstanding previous refractoriness to divers therapeutic measures.
An unusual cause of central cyanosis in a patient with rheumatic heart disease.
Authors: P K Lee, S Y So, J S Chow
Journal: Thorax (1986)

Rheumatic valvular heart disease, especially mitral stenosis, is commonly associated with abnormal pulmonary function.Systemic arterial oxygen saturation in such patients, how- ever, almost always stays within the normal range or is only minimally reduced,' except perhaps during spells of acute pulmonary oedema.We report a case of "silent" pulmonary arteriovenous fistula occurring in a patient with aortic and mitral stenosis.The only clues to the diagnosis before car- diac catheterisation were the presence of central cyanosis and a suspicious calcified hilar shadow.
The Carpal Tunnel Syndrome and Colles' Fractures
Authors: Andrew C. Lynch
Journal: JAMA (1963)

From an investigation extending over the past 10 years and consisting of 20 extremities with median nerve compression associated with Colles' fracture in 19 patients, the authors make the following observations: (1) The carpal tunnel syndrome is frequently associated with a Colles fracture. (2) Median nerve compression often occurs after immobilization with wrist in Cotton-Loder position. Consequently, this position should rarely, if ever, be used in treatment. (3) Surgical decompression of the median nerve, by releasing the transverse carpal ligament, is indicated when pain and loss of sensation are severe. (4) Nonoperative treatment to control edema, including injection of hydrocortisone into the carpal tunnel, is usually adequate in milder cases. (5) Factors associated with the carpal tunnel syndrome that follows a Colles fracture may be classified as primary (median nerve caught between fractured ends of radius) and delayed (edema, position of hand during immobilization, and tenosynovitis).
A Prospective Study of Asymptomatic Carriers of the Factor V Leiden Mutation To Determine the Incidence of Venous Thromboembolism
Authors: Saskia Middeldorp, Johan R. Meinardi, Maria M.W. Koopman, Elisabeth C.M. van Pampus, Karly Hamulyák, Jan van der Meer, Martin H. Prins, Harry R. Büller
Journal: Annals of Internal Medicine (2001)

Background: The factor V Leiden mutation is a common genetic defect associated with an increased risk for venous thromboembolism. The clinical implications for asymptomatic carriers of this mutation and, consequently, the usefulness of screening families in which a proband has both the mutation and venous thromboembolism are unclear. Objective: To determine the incidence of venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation. Design: Prospective cohort study. Setting: University hospitals in the Netherlands. Participants: 470 asymptomatic carriers of the factor V Leiden mutation (234 men, 236 women; mean age, 43 years [range, 15 to 88 years]), 12 of whom were homozygous. Carriers were identified by screening the first-degree relatives (>15 years of age) of 247 symptomatic probands. Measurements: Objectively diagnosed episodes of venous thromboembolism and the relationship between incidence and exposure to high-risk situations. Results: Nine venous thromboembolic events were observed in 1564 observation-years, resulting in an annual incidence of 0.58% (95% CI, 0.26% to 1.10%). The incidence of spontaneous venous thromboembolism was 0.26% (CI, 0.07% to 0.65%) per year; 3.5% (CI, 0.1% to 17.8%) per episode of surgery, trauma, or immobilization; 0.0% (CI, 0.0% to 19.5%) per pregnancy; 1.8% (CI, 0.4% to 5.2%) per year of oral contraceptive use; and 2.9% (CI, 0.8% to 15.3%) per year of use of hormone replacement therapy. Conclusions: The absolute annual incidence of spontaneous venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation is low and does not justify routine screening of the families of symptomatic patients.
The role of thoracic duct lymph in gastrin transport and gastric secretion
Authors: B. G. Clendinnen, D. D. Reeder, J. C. Thompson
Journal: Gut (1973)

The effect of thoracic lymph diversion on gastric secretion has been studied in dogs. In addition, the concentration of gastrin in thoracic duct lymph of nine dogs and two patients has been measured before and during antral stimulation with either food or acetylcholine. The secretory studies do not support the concept that there is a significant gastric secretagogue in thoracic duct lymph. The amount of gastrin carried in thoracic duct lymph as determined by radioimmunoassay is far less than that necessary to evoke a gastric secretory response.
Acute, Transient Encephalopathy in Young Children Following Smallpox Vaccination
Authors: Dick Hoefnagel
Journal: JAMA (1962)

Four young children, who were otherwise normal, developed an illness characterized by the sudden onset of an isolated, prolonged generalized seizure 7 to 8 days following smallpox vaccination. This convulsive episode was unlike that of a simple febrile convulsion, commonly seen in this age group. A rapid, complete recovery and an absence of further convulsive disorder were noted in all 4 children. The significance of this clinical picture is discussed, particularly in view of recent studies of the nervous system complications following smallpox vaccination.
Why are patients with acute stroke admitted to hospital?
Authors: J. Andrews
Journal: BMJ (1986)

computed tomography2 but lacks the ability to provide a differential diagnosis.Recently interest has focused on radiopharmaceuticals which allow images to be made showing regional cerebral blood flow.Two agents in par- ticular have proved useful, '231 isopropylamphetamine (IMP)3 and, more recently, 99Tc hexamethyl propyleneamineoxime (HM-PAO).4These agents not only provide the ability to identify the presence of both tumours' and infarcts,6 although both appear as areas of reduced cerebral blood flow, but they also show distinctive patterns of perfusion for some types of dementia.78We have shown that, in particular, the pattern in Alzheimer's disease is ofa bilateral reduction in perfusion in the temporo- parieto-occipital regions while in multi-infarct dementia the uptake pattern varies from normal to that of gross focal defects.9Our recent work indicates that in Huntington's chorea there may be reduced perfusion in the head of the caudate nucleus.9'mTc HM-PAO, which offers several technical advantages over '23I IMP, should be available commercially in the near future, and the imaging equipment, a tomographic gammacamera, is avail- able in most hospitals.The study is simple to perform, requiring one intravenous injection of the radiopharmnaceutical and about 30 minutes' imagig tme.
Clinical and molecular predictors of disease severity and survival in chronic lymphocytic leukemia
Authors: J. Brice Weinberg, Alicia D. Volkheimer, Youwei Chen, Bethany E. Beasley, Ning Jiang, Mark C. Lanasa, Daphne Friedman, Gina Vaccaro, Catherine W. Rehder, Carlos M. DeCastro, David A. Rizzieri, Louis F. Diehl, Jon P. Gockerman, Joseph O. Moore, Barbara K. Goodman, Marc C. Levesque
Journal: American Journal of Hematology (2007)

Several parameters may predict disease severity and overall survival in chronic lymphocytic leukemia (CLL). The purpose of our study of 190 CLL patients was to compare immunoglobulin heavy chain variable region (IgV(H)) mutation status, cytogenetic abnormalities, and leukemia cell CD38 and Zap-70 to older, traditional parameters. We also wanted to construct a simple, inexpensive prognosis score that would significantly predict TTT and survival in patients at the time of diagnosis and help practicing clinicians. In univariate analyses, patients with higher clinical stage, higher leukocyte count at diagnosis, shorter leukocyte doubling time, elevated serum lactate dehydrogenase (LDH), unmutated immunoglobulin heavy chain variable region (IgV(H)) genes, and higher CD38 had a shorter overall survival and time-to-treatment (TTT). CLL cell Zap-70 expression was higher in patients with unmutated IgV(H), and those with higher Zap-70 tended to have shorter survival. IgV(H)4-34 or IgV(H)1-69 was the most common IgV(H) genes used (16 and 12%, respectively). Of those with IgV(H)1-69, 86% had unmutated IgV(H) and had a significantly shorter TTT. A cytogenetic abnormality was noted in 71% of the patients tested. Patients with 11q22 del and 17p13 del or complex abnormalities were significantly more likely to have unmutated IgV(H). We found that a prognostic score constructed using modified Rai stage, cellular CD38, and serum LDH (parameters easily obtained clinically) significantly predicted TTT and survival in patients at the time of diagnosis and performed as well or better than models using the newer markers.
Anemia during treatment with peginterferon Alfa-2b/ribavirin and boceprevir: Analysis from the serine protease inhibitor therapy 2 (SPRINT-2) trial
Authors: Mark S. Sulkowski, Fred Poordad, Michael P. Manns, Jean-Pierre Bronowicki, K. Rajender Reddy, Stephen A. Harrison, Nezam H. Afdhal, Heather L. Sings, Lisa D. Pedicone, Kenneth J. Koury, Vilma Sniukiene, Margaret H. Burroughs, Janice K. Albrecht, Clifford A. Brass, Ira M. Jacobson
Journal: Hepatology (2012)

Boceprevir (BOC) added to peginterferon alfa-2b (PegIFN) and ribavirin (RBV) significantly increases sustained virologic response (SVR) rates over PegIFN/RBV alone in previously untreated adults with chronic hepatitis C genotype 1. We evaluate the relationship of incident anemia with triple therapy. A total of 1,097 patients received a 4-week lead-in of PegIFN/RBV followed by: (1) placebo plus PegIFN/RBV for 44 weeks (PR48); (2) BOC plus PegIFN/RBV using response-guided therapy (BOC/RGT); and (3) BOC plus PegIFN/RBV for 44 weeks (BOC/PR48). The management of anemia (hemoglobin [Hb]<10 g/dL) included RBV dose reduction and/or erythropoietin (EPO) use. A total of 1,080 patients had ≥1 Hb measurement during treatment. The incidence of anemia was 50% in the BOC arms combined (363/726) and 31% in the PR48 arm (108/354, P<0.001). Among BOC recipients, lower baseline Hb and creatinine clearance were associated with incident anemia. In the BOC-containing arms, anemia was managed by the site investigators as follows: EPO without RBV dose reduction, 38%; RBV dose reduction without EPO, 8%; EPO with RBV dose reduction, 40%; and neither RBV dose reduction nor EPO, 14%. SVR rates were not significantly affected by management strategy (70%-74%), and overall patients with anemia had higher rates of SVR than those who did not develop anemia (58%). Serious and life-threatening adverse events (AEs) and discontinuations due to AEs among BOC-treated patients did not differ by EPO use.With BOC/PR therapy, SVR rates in patients with incident anemia were higher than nonanemic patients and did not vary significantly according to the investigator-selected approach for anemia management. Prospective studies are needed to confirm this observation.
Liver Transplantation for Type IV Glycogen Storage Disease
Authors: Rick Selby, Thomas E. Starzl, Eduardo Yunis, Barbara I. Brown, Ross S. Kendall, Andreas Tzakis
Journal: New England Journal of Medicine (1991)

Type IV glycogen storage disease is a rare autosomal recessive disorder (also called Andersen’s disease1 or amylopectinosis) in which the activity of branching enzyme alpha-1, 4-glucan: alpha-1, 4-glucan 6-glucosyltransferase is deficient in the liver as well as in cultured skin fibroblasts and other tissues.2,3 This branching enzyme is responsible for creating branch points in the normal glycogen molecule. In the relative or absolute absence of this enzyme, an insoluble and irritating form of glycogen, an amylopectin-like polysaccharide that resembles plant starch, accumulates in the cells. The amylopectin-like form is less soluble than normal glycogen, with longer outer and inner chains and fewer branch points. The clinical onset of the disease is insidious, with nonspecific gastrointestinal symptoms at first, followed by progressive hepatosplenomegaly, portal hypertension, ascites, and hepatic failure. Children with this disorder usually die of hepatic cirrhosis by the age of two to four years. 4–8 In exceptional cases, cardiomyopathy,5–7,9 neurologic syndromes — including tremors, seizures, and dementia10,11 — or variable manifestations of myopathy5,12,13 have been reported. In patients with these unusual symptoms, the clinical onset is frequently later than in typical cases, and death most often results from cardiac failure.

Liver transplantation for Type IV glycogen storage disease was attempted in 1972; the recipient died 110 days later after the rejection of the first liver transplant and attempted re transplantation.14 Liver transplantation was first performed successfully in September 1984 in Patient 1 of this series; since that time we have treated six more such patients. Our experience with these seven patients forms the basis of this report.