tbuckley/cabot-search huggingface dataset:
Mechanisms of Action of Cholestyramine in the Treatment of Hypercholesterolemia
Authors: D. J. NAZIR, L. HORLICK, B. J. KUDCHODKAR, H. S. SODHI
Journal: Circulation (1972)

Cholestyramine (12 g/day) was administered to four subjects with familial hyperchloesterolemia (type II) for 12 to 15 days. Plasma cholesterol values fell by 24 to 28% in all subjects. Total endogenous fecal steroids increased from 2.0 to 2.5 times over the control values. This increment was mainly in the acidic fraction which increased from 1.4 to 6.5 times during treatment. The neutral steroid fraction showed a slight increase (nonsignificant) in two subjects and a significant increase ( P &lt; 0.05) in one subject. The total fecal steroid increment was considerably in excess of the decrement in plasma cholesterol, thus indicating either (a) a substantial increase in cholesterol synthesis, (b) a transfer of cholesterol from depots, or (c) both. Plasma cholesterol specific activity time curves showed a sharp increase in the slope immediately after the commencement of treatment, reflecting an increase in the rate of entry of unlabeled cholesterol into the readily miscible pool. Since cholestyramine did not change the absorption of the dietary cholesterol, the increase in the contribution of unlabeled cholesterol could only be from an increase in endogenous synthesis. In accordance with previous findings from this laboratory, no evidence of degradation of the steroid nucleus was detected during its passage through the gastrointestinal tract.
Progress in Research on Pulmonary-Artery Catheters
Authors: Polly E. Parsons
Journal: New England Journal of Medicine (2003)

Pulmonary-artery catheters are widely used in critically ill patients both for diagnosis and to guide therapy. According to current estimates, there are more than 1.2 million pulmonary-artery catheters placed annually in the United States, with associated costs of over $2 billion.1 A layperson might assume that if a form of medical technology is so widely used, there must be clear-cut indications for its clinical use. Unfortunately, that would be an incorrect assumption. The indications for placement of a pulmonary-artery catheter, the interpretation of the data generated by the catheter, and the goals for therapy directed by it all remain to . . .
The Genetical Impact of Medicine
Authors: PETER MEDAWAR
Journal: Annals of Internal Medicine (1967)

Article1 September 1967The Genetical Impact of MedicinePETER MEDAWAR, D.SC., F.A.C.P. (HON.)PETER MEDAWAR, D.SC., F.A.C.P. (HON.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-67-3-28 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe theme of my contribution to this important symposium is to be the impact of medicine and medical research on the genetic welfare of human beings. I should explain that Prof. Lederberg and I have agreed on a division of labor that allots the domain of genetics to me, while I—not to be outdone in magnanimity—have made over all my rights in the field of transplantation to Dr. Thomas Starzl.Genetics is in itself a sober and austere discipline, but the genetic welfare of mankind is a subject that arouses strong passions. I believe that the problems before us can... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1967Volume 67, Issue 3_Part_2Page: 28-31KeywordsGeneticsHuman geneticsTransplantation Issue Published: 1 September 1967 PDF DownloadLoading ...
DEHYDRATION AND EPILEPSY
Authors: Temple Fay
Journal: JAMA (1933)

<h3>To the Editor:</h3> —I have noted inThe Journal, April 1, the report on dehydration and epilepsy by Drs. Fetterman and Kumin, concerning twenty-one epileptic patients observed for a period of about one month. I feel that it is dangerous to reduce a patient's fluids to 100 cc. a day; the purposes and objectives of the method are ignored when carried to this extreme degree. The objective is not to subtract fluid to an intolerable degree, from the customary routine of the patient, but to subtract fluid from the patient's body fluid reservoirs. Unless the patient demonstrates actual loss of body weight, there is no subtraction or no real dehydration. A pint, or 500 cc., weighs approximately one pound, and unless water is subtracted from the body tissue reservoirs there will arise no change in cerebrospinal fluid volume or pressure. If the patient receives sufficient liquids in other forms, such
Study of immunoglobulins in pleura and pleural effusions.
Authors: L Telvi, F Jaubert, A Eyquem, J P Andreux, F Labrousse, J Chretien
Journal: Thorax (1979)

The protein concentration of 35 pleural effusions was compared with that in the serum. The ratio of the pleural and serum concentration of albumin, IgG, IgA, and IgM is always below unity and appears to have no diagnostic value. However, the ratio of the concentration of these proteins was inversely related to their molecular weight. The underlying mechanism in malignant and inflammatory effusions appear similar and is in keeping with a diffusion process. Immunofluorescent staining of the pleura suggests the intercellular passage of the proteins through the mesothelial barrier.
Physiologically based pharmacokinetic model for the inhibition of acetylcholinesterase by organophosphate esters.
Authors: J M Gearhart, G W Jepson, H J Clewell, M E Andersen, R B Conolly
Journal: Environmental Health Perspectives (1994)

Organophosphate (OP) exposure can be lethal at high doses while lower doses may impair performance of critical tasks. The ability to predict such effects for realistic exposure scenarios would greatly improve OP risk assessment. To this end, a physiologically based model for diisopropylfluorophosphate (DFP) pharmacokinetics and acetylcholinesterase (AChE) inhibition was developed. DFP tissue/blood partition coefficients, rates of DFP hydrolysis by esterases, and DFP-esterase bimolecular inhibition rate constants were determined in rat tissue homogenates. Other model parameters were scaled for rats and mice using standard allometric relationships. These DFP-specific parameter values were used with the model to simulate pharmacokinetic data from mice and rats. Literature data were used for model validation. DFP concentrations in mouse plasma and brain, as well as AChE inhibition and AChE resynthesis data, were successfully simulated for a single iv injection. Effects of repeated, subcutaneous DFP dosing on AChE activity in rat plasma and brain were also well simulated except for an apparent decrease in basal AChE activity in the brain which persisted 35 days after the last dose. The psychologically based pharmacokinetic (PBPK) model parameter values specific for DFP in humans, for example, tissue/blood partition coefficients, enzymatic and nonenzymatic DFP hydrolysis rates, and bimolecular inhibition rate constants for target enzymes were scaled from rodent data or obtained from the literature. Good agreement was obtained between model predictions and human exposure data on the inhibition of red blood cell AChE and plasma butyrylcholinesterase after an intramuscular injection of 33 micrograms/kg DFP and at 24 hr after acute doses of DFP (10-54 micrograms/kg), as well as for repeated DFP exposures.(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary involvement in Fabry disease.
Authors: L K Brown, A Miller, A Bhuptani, M F Sloane, M I Zimmerman, G Schilero, C M Eng, R J Desnick
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Fabry disease is an X-linked inborn error of metabolism resulting from deficient activity of alpha-galactosidase A. Although several case reports have suggested an association between Fabry disease and airway obstruction, this has not been investigated in a large series of patients. We studied 25 unselected, consecutive, enzymatically diagnosed men referred to a General Clinical Research Center for evaluation. Thirty-six percent complained of dyspnea, and 24% had cough and/or wheezing. Symptoms were similar in smokers and nonsmokers. Nine (36%) had airway obstruction on spirometry; this finding was associated with age > or = 26 yr (p < 0.05) and dyspnea or wheezing (p < 0.005), but only weakly with smoking (p = 0.062). Five of eight patients responded to bronchodilators, but all 10 methacholine challenges were negative. Chest radiographs revealed normal lung fields in 24 patients and streaky bibasilar densities in one. No pulmonary uptake occurred on 67Ga citrate scans (18 patients) and 111In-tagged leukocyte scans (16 patients). Specific alpha-galactosidase A mutations were identified in 17 patients; all three patients with frameshift mutations and both subjects with the D264V missense mutation had obstructive impairment. We conclude that airway obstruction commonly occurs in patients with Fabry disease regardless of smoking history, and it increases with age. The presence of obstruction may be associated with certain mutations and most likely results from fixed narrowing of the airways by accumulated glycosphingolipid.
A double antibody radioimmunoassay for canine cardiac cathepsin D
Authors: A. M SAMAREL, E. A OGUNRO, A. G FERGUSON, M. LESCH
Journal: Cardiovascular Research (1981)

We have developed a sensitive double antibody radioimmunoassay for measuring canine cardiac cathepsin D. Radioiodinated cathepsin D was prepared by chloramine T oxidation using a highly purified source of enzyme. High avidity antiserum to the canine cardiac enzyme was raised in rabbits. Antibody-bound cathepsin D was separated from free enzyme using goat anti-rabbit IgG second antibody. The least amount of immunoreactive enzyme measurable in the radioimmunoassay was 2.4 ng.cm-3 as determined by antibody titration. The assay was linear for concentrations of enzyme in the range of 10 to 120 ng.cm-3. Within-assay and between-assay variations were 12%. The radioimmunoassay described was used to measure the immunoreactive cathepsin D content of the 100 000 x g supernatant fraction of canine myocardial homogenates.
Analysis of cytokine signaling in patients with extrinsic asthma and hyperimmunoglobulin E
Authors: Rachel L. Miller, Thomas M. Eppinger, David McConnell, Charlotte Cunningham-Rundles, Paul Rothman
Journal: Journal of Allergy and Clinical Immunology (1998)

Background: Recent data suggest that the regulation of class switching to IgE by cytokines is mediated by STAT transcription factors. The induction of IgE by IL-4 and IL-13 occurs through the activation of the intracellular signal-transducing protein Stat6, whereas the inhibition of IgE class switching by interferon-γ (IFN-γ) occurs through the activation of Stat1.Objective: We hypothesized that in extrinsic asthma or in cases of markedly elevated IgE (ie, hyperimmunoglobulin E [HIE]) increased levels of IgE may be associated with alterations in the cytokine levels or the activation of Stat6.Methods: PBMCs and sera from 8 patients with extrinsic asthma (mean IgE, 285 ± 100 IU/mL), 3 patients with HIE (mean IgE, 7050 ± 1122 IU/mL), and 14 nonatopic control subjects (mean IgE, 112 ± 28 IU/mL) were analyzed.Results: The mean IL-4 level detected by ELISA was much greater in patients with HIE than control subjects (88.6 ± 11.5 pg/mL vs 11.5 ± 7.1 pg/mL, P = .005), and increased IL-4 levels among patients with both asthma and HIE correlated with the increased IgE levels. In contrast, IL-13 levels were not elevated. Levels of Stat6 protein present in PBMCs did not differ in the patients and control subjects. Examination of Stat6 DNA-binding activity demonstrated no activation of IL-4 signaling in patients with either HIE or acute asthma. Interestingly, evidence for the presence of B cells that have already switched to IgE was seen in PBMCs of several patients with asthma or HIE.Conclusion: These results indicate that (1) IgE production in asthma and HIE usually is associated with elevated levels of IL-4, but not IL-13, in the peripheral blood; (2) the increased sera IL-4 levels in asthma and HIE are not sufficient to induce Stat6 activation in PBMCs; and (3) evidence of switch recombination to ϵ may be detected in isolated cases of elevated IgE. This implies that high levels of IgE in these patients either results from B cells that have already undergone class switching, from Ig class switching that is localized to target tissues, or both. (J Allergy Clin Immunol 1998;102:503-11.)
A CAT reporter construct allows ultrasensitive estimation of TNF synthesis, and suggests that the TNF gene has been silenced in non-macrophage cell lines.
Authors: B Beutler, T Brown
Journal: Journal of Clinical Investigation (1991)

We have prepared a construct (designated CATTNF) in which the mouse TNF (cachectin) coding sequence is replaced by a sequence encoding chloramphenicol acetyltransferase (CAT), with preservation of the TNF promoter and 3'-untranslated sequences known to be important in the regulation of gene expression. When activated by LPS, permanently transfected RAW 264.7 (mouse macrophage) cells synthesize large quantities of CAT. Unlike TNF itself, CAT is nonsecreted and quite stable in the macrophage cytoplasm. Fewer than 1,000 LPS-induced macrophages can easily be detected by CAT assay. Cells maintain the ability to respond to LPS in vivo; as such, when injected intravenously, they accurately report conditions required for the production of TNF in diverse tissues. These cells may thus be used for the detection of cachectin/TNF synthesis in mice under conditions in which endogenously produced cachectin/TNF would be undetectable. Studies of the expression of CATTNF in nonmacrophage cell lines have revealed that the modified TNF gene is constitutively expressed in L-929 cells, but that its expression is tightly suppressed in HeLa cells and in NIH 3T3 cells. This finding would suggest that certain non-macrophage cells are potentially capable of utilizing the TNF promoter and translating the TNF mRNA; however, the endogenous gene has been developmentally silenced.
AB0242 The evaluation of methotrexate related lymphoproliferative disease.
Authors: M. Mukai, M. Kanda, M. Kondo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It is well known that EB virus related lymphoproliferative disease (LPD) is related with immunosuppressive treatment. It has been reported that EB virus related LPD developed in the patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). <h3>Objectives</h3> As MTX doses for RA in Japan was limited to 8 mg/week until 2011, we evaluated the clinical character of MTX related LPD in our hospital. <h3>Methods</h3> We retrospectively picked up the MTX-related LPD cases from our patients since 2002. <h3>Results</h3> Ten cases of MTX related LPD were found, 9 RA and 1 dermatomyositis. The ratio of male to female was 3:7. The average age of onset of LPD was 67.8±9.1 years old. The average duration of administration of MTX was 67.0±38.2 months (30-147 months). Average dose of MTX was 8.0±1.7 mg/week (6-12 mg). Corticosteroid was used in 5 cases, and 4 cases with RA were treated with 5 mg/day, and a case with dermatomyositis was treated with 10 mg/day. Biologics were administered in 5 cases, and all was infliximab. Folic acid was used in 4 cases. The pathology showed that 7 cases were diffuse large B cell lymphoma, 2 cases were Hodgkin's disease, and one unknown case was included. EB virus was demonstrated in 9 cases. The origins of LPD indicated that 3 cases were lymph nodes and 7 cases were extralymphatic site such as subcutaneous, stomach, adrenal grand, or lumbar spine. The prognosis were different in each case: LPD was disappeared after the discontinuance of MTX in 5 cases, clinical remission was achieved with radiation to lumbar spine and chemotherapy including rituximab in a case (but, he was dead by lung cancer 3 years later), relapse after chemotherapy including rituximab in a case with Hodgkin's disease, dead during chemotherapy in a case, and dead after relapse during treatment rituximab. <h3>Conclusions</h3> MTX related LPD could be occurred in patients with long period of treatment with MTX, but not related with the dose of MTX. It could be occurred with severe type of RA who needed biologic agents. EB virus could be demonstrated in the tissue. The location of LPD was much more in extralymphatic site than in lymph node. Many cases showed diffuse large B cell lymphoma type. MTX related LPD was disappeared in many cases by stopping MTX, but some case showed relapse. In our case, the prognosis in the cases treated with rituximab was showed as very poor because of unknown reason. <h3>Disclosure of Interest</h3> None Declared
Comparison of the acute response to meals enriched with cis- or trans-fatty acids on glucose and lipids in overweight individuals with differing FABP2 genotypes
Authors: Michael Lefevre, Jennifer C. Lovejoy, Steven R. Smith, James P. DeLany, Catherine Champagne, Marlene M. Most, Yvonne Denkins, Lilian de Jonge, Jennifer Rood, George A. Bray
Journal: Metabolism (2005)
Is there an advantage to be gained from adding digital image cytometry of brush cytology to a standard biopsy protocol in patients with Barrett’s esophagus?
Authors: J. Borovicka, R. Schönegg, M. Hell, D. Kradolfer, P. Bauerfeind, G. Dorta, P. Netzer, J. Binek, C. Meyenberger, J. Fischer, P. Spieler
Journal: Endoscopy (2009)

Background and study aims: The current gold standard in Barrett’s esophagus monitoring consists of four-quadrant biopsies every 1 – 2 cm in accordance with the Seattle protocol. Adding brush cytology processed by digital image cytometry (DICM) may further increase the detection of patients with Barrett’s esophagus who are at risk of neoplasia. The aim of the present study was to assess the additional diagnostic value and accuracy of DICM when added to the standard histological analysis in a cross-sectional multicenter study of patients with Barrett’s esophagus in Switzerland.
Polymorphic light eruption and skin cancer prevalence: is one protective against the other?
Authors: S. Lembo, J. Fallon, P. O’Kelly, G.M. Murphy
Journal: British Journal of Dermatology (2008)

Ultraviolet (UV) radiation (UVR) interacts with chromophores in cutaneous cells with consequent antigenicity. The normal response to this is a downregulation of immune responsiveness. Failure of the immune system to downregulate and to ignore transient photoantigens in human skin results in polymorphic light eruption (PLE), the commonest of the photodermatoses. UVR initiates and promotes skin cancer (SC): UV-induced immunosuppression permits the expansion of UV-mutated clones of cells which ultimately lead to SC.Because there is increased immune surveillance and resistance to immune suppression following UVR exposure in PLE one might expect a protective effect of PLE against SC and, conversely, a reduced risk of PLE among patients with SC.We therefore constructed a prospective case-control study to see if this were the case. Two groups were studied: a group comprising 214 patients with SC and 210 gender- and aged-matched controls, and a group comprising 100 patients with PLE and 155 gender- and aged-matched controls. Each participant answered a questionnaire aimed at establishing personal and family history of SC and photodermatoses. Skin type and exposure to UVR were also documented.The prevalence of PLE in people with SC was 7.5%, compared with 21.4% for controls (P<0.001). The prevalence of SC in patients with PLE was 4% compared with 7.1% for controls.Our results show (i) strong evidence of reduced PLE in patients with SC, and (ii) a trend for reduced SC in patients with PLE. The immunological basis of PLE may therefore confer protection against SC.
Commercially available biological mesh does not prevent stricture after esophageal mucosectomy
Authors: Steve Schomisch, Liming Yu, Yuhsin Wu, Eric Pauli, Cassandra Cipriano, Amitabh Chak, Richard Lash, Jeffrey Ponsky, Jeffrey Marks
Journal: Endoscopy (2013)

<b>Background and study aims:</b> Endoscopic mucosal resection (EMR) offers a minimally invasive therapy for advanced esophageal dysplasia and early cancers but stricture formation limits its applicability. We aimed at assessing the efficacy of placement of a commercially available biological mesh for preventing stricture formation following esophageal EMR. <b>Methods:</b> 25 swine were submitted to circumferential esophageal EMR with 10-cm extent and divided in five groups: one group with EMR only (control); one receiving an uncovered stent (stent-only group); and three groups receiving a stent covered with one of three extracellular matrices, namely small intestine submucosa (SIS group), acellular dermal matrix (ADM group), or urinary bladder matrix (UBM group). Stricture formation was evaluated with weekly esophagograms. <b>Results:</b> The stent-only group had significantly less stricture formation and survival was extended compared with controls (4.8 vs. 2.4 weeks). Compared with stenting only, the addition of a biological mesh did not reduce stricture formation: percent reductions in esophageal diameter for the groups were SIS 86 %, ADM 94 %, and UBM 94 %, compared with 82 % in the stent-only group. <b>Conclusions:</b> Placement of commercially available biological meshes did not alter remodeling sufficiently to prevent stricture formation after esophageal EMR.
Bilateral Superior Vena Cava
Authors: Andrew C Fry, Paul Warwicker
Journal: New England Journal of Medicine (2007)

A 67-year-old man receiving hemodialysis because of kidney failure resulting from renovascular disease was admitted to the hospital for revision of dialysis access. Six months earlier, a dual-chamber, permanent pacemaker had been implanted in the right side of the chest for the treatment of complete heart block. The dialysis catheter, inserted into the left internal jugular vein under fluoroscopic guidance, showed a left superior vena cava draining into the right atrium through a coronary sinus. A chest radiograph showed the pacemaker, with leads in the right subclavian vein and right superior vena cava, and a catheter in the left internal . . .