tbuckley/cabot-search huggingface dataset:
Sulfonylurea-Sensitive K+ Transport is Involved in Cl− Secretion and Cyst Growth by Cultured ADPKD Cells
Authors: Lawrence P. Sullivan, Darren P. Wallace, Tony Gover, Paul A. Welling, Tamio Yamaguchi, Robin Maser, Jason W. Eppler, Jared J. Grantham
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Transepithelial chloride and fluid secretion by many types of epithelia involves activation of a conductive K+ pathway that serves to support the electrochemical driving force for Cl− secretion. This study sought to determine if such a pathway is involved in Cl− and fluid secretion by the cystic epithelia in autosomal dominant polycystic kidney disease (ADPKD). Primary cultures of cells derived from the cysts of patients with ADPKD were used. Confluent monolayers of these cells, mounted in Ussing chambers, were stimulated to secrete Cl− by application of the adenylyl cyclase agonist, forskolin. The effects of various K+ channel blockers on the increase in short-circuit current (Isc) generated by active Cl− secretion were determined. Charybdotoxin, an inhibitor of Ca2+-sensitive K+ channels exerted no effect. Similarly, the chromanole 293B, an inhibitor of cAMP-induced K+ conductance, exerted no effect on cAMP-dependent anion secretion. Glibenclamide, an inhibitor of ATP-sensitive K+ channels and the cystic fibrosis transmembrane conductance regulator (CFTR), modestly inhibited the forskolin-stimulated current when applied to the apical surface of the monolayers, suggesting a relatively weak effect on CFTR. Basolateral application of glibenclamide inhibited Isc to a greater extent. This latter effect may be due to inhibition of a K+-conductive transport step. Glibenclamide exerted little effect on the Isc of nonstimulated monolayers. Cyst growth in ADPKD is driven by cell proliferation and Cl− and fluid secretion. The effect of glibenclamide on the growth of cysts formed within a collagen gel by cultured ADPKD cells was tested. Addition of glibenclamide to the media bathing the cysts inhibited their growth. Glibenclamide also blocked the formation of cysts when it was added to the media at the time the cells were seeded within the collagen gel. Glibenclamide was also found to inhibit the proliferation of ADPKD cells. RT-PCR analysis demonstrated that the ATP-sensitive K+ channel, Kir 6.2, is expressed in cultured ADPKD cells and in normal human kidney. These results suggest that ATP-sensitive K+ channel blockers should be investigated as possible therapeutic agents to inhibit cyst growth in ADPKD.
Jaundice Following the Administration of Niacin
Authors: A. Arthur Sugerman
Journal: JAMA (1974)

CHOLESTATIC jaundice is a recognized complication of massive doses of niacin.<sup>1</sup>Recovery usually occurs after the therapy is discontinued. The present case is of interest in that the dosage was moderate (750 mg daily) and the duration relatively short (less than three months). Nevertheless, a reaction to niacin appears to be a reasonable explanation of the patient's jaundice. <h3>Report of a Case</h3> A 69-year-old white man became bored with his inactive retirement and attempted suicide by car exhaust fumes. Five months earlier he had had an apparent stroke and developed a parkinsonian tremor, difficulty in walking, episodic memory difficulties, and increasing depression. He was lethargic but not comatose when admitted to a general hospital for emergency treatment after his suicide attempt, and three days later he was transferred to a psychiatric hospital. Findings were consistent with organic brain syndrome, with psychological tests indicating intellectual deterioration and right-hemisphere damage. The
OPEN-ANGLE GLAUCOMA: AN OPPORTUNITY FOR EARLY DETECTION
Authors: Carl Kupfer
Journal: JAMA (1965)

Elsewhere in this issue (p 526) Cowan calls attention to the need for the general practitioner and the internist to question every patient about a family history of glaucoma and to use the tonometer routinely for measuring intraocular pressure. Cowan indicates that among children, siblings, and parents of patients with open-angle glaucoma, the incidence of glaucoma or borderline glaucoma was 6.6%, which is three times the expected rate among the general population. He might have added also that about 50% of all direct offspring of patients with open-angle glaucoma have suspected glaucoma, on the basis of a positive water-drinking test.<sup>1</sup>Just as corticosteroids can provoke an abnormal glucose tolerance curve in patients having no evidence of diabetes, topically applied corticosteroids provoke an elevation of intraocular pressure in about one quarter of the normal population<i>not</i>having a parent with open-angle glaucoma. However, topical corticosteroids will induce an intraocular pressure
Intimal hyperplasia after vascular injury is inhibited by antisense cdk 2 kinase oligonucleotides.
Authors: R Morishita, G H Gibbons, K E Ellison, M Nakajima, H von der Leyen, L Zhang, Y Kaneda, T Ogihara, V J Dzau
Journal: Journal of Clinical Investigation (1994)

The cell cycle regulatory enzyme, cdk (cyclin-dependent kinase) 2 kinase, is activated in the rat carotid artery after balloon angioplasty injury, and may mediate smooth muscle proliferation. To test the hypothesis that inhibition of the expression of this key enzyme can inhibit intimal hyperplasia, we studied the effect of antisense phosphorothioate oligodeoxynucleotides (ODN) against cdk 2 kinase administered by intraluminal delivery using hemagglutinating virus of Japan (HVJ)-liposome-mediated transfer. The specificity of antisense cdk 2 ODN was confirmed by the observation that mRNA level of cdk 2 kinase in injured vessels was markedly diminished by the antisense ODN treatment. At 2 wk after transfection, antisense cdk 2 ODN treatment (15 microM) resulted in a significant inhibition (60%) in neointima formation, compared with sense ODN-treated and untreated vessels. Since we have previously observed that cell division cycle 2 kinase mRNA was also activated after vascular injury, we administered the combination of antisense cdc 2 and cdk 2 ODN in this study. Antisense cdc 2 ODN alone (15 microM) only reduced intimal formation by 40%. Combined antisense treatment resulted in near complete inhibition of neointima formation. To understand the mechanism of the sustained effect of a single antisense ODN administration, we examined kinetics of ODN in the vessel wall. Using phosphorothioate FITC-labeled ODN, we transfected carotid artery using the HVJ-liposome method. Fluorescence localized immediately to the medial layer, and persisted up to 2 wk after transfection. These results demonstrate that a single intraluminal administration of antisense ODN directed to cell cycle regulatory genes (e.g., cdk 2 kinase) using the HVJ method can result in a sustained inhibition of neointima formation after balloon angioplasty in rat carotid injury model.
ABC of antithrombotic therapy: Antithrombotic therapy in special circumstances. II---In children, thrombophilia, and miscellaneous conditions
Authors: B. Jilma
Journal: BMJ (2003)

Most of the recommendations on antithrombotic therapy in children are based on the extrapolation of results from randomised studies of adults or from small cross sectional, and mainly retrospective, clinical studies of children. Although antithrombotic therapy in children usually follows the same indications as in adults, the distribution of diseases requiring antithrombotic therapy differs in the paediatric population. For example, some predisposing factors for thromboembolism are encountered only in paediatric populations. Most of the indications for antithrombotic therapy in children arise because of an underlying medical disorder or an intervention for the management of the disorder. Management of antithrombotic therapy in children differs from that in adults because of ongoing changes in physiology that may alter the thrombotic process and potentially influence the response of the body to antithrombotic therapy.



Indications for antithrombotic therapy in children



### Drug treatments

#### Antiplatelet treatment

Aspirin, dipyramidole, and indomethacin are probably the most used antiplatelet treatments among children. Low doses of aspirin (antiplatelet doses) usually have minimal side effects in children, but in general aspirin should not be prescribed to children aged  40 mg/kg).

#### Heparin

Heparin is probably the most commonly used antithrombotic drug in children. Varying concentrations of antithrombin in the body during different developmental stages mean that the therapeutic concentration of heparin in children has to be maintained by regular checks of the activated partial thromboplastin time (APTT) or anti-Xa concentrations. The recommended therapeutic level of APTT is the one which corresponds to a heparin concentration of 0.2-0.4 U/ml or an anti-Xa concentration of 0.3-0.7 U/ml.

View this table:

Adjusting low molecular weight heparin in children



In children, the advantages of low molecular weight heparin over unfractionated heparin are similar to those in adults. In addition, low …
Non-invasive diagnosis of liver fibrosis progression by a clinical and US-doppler predictive model during chronic HCV infection
Authors: K. Mattiello, A. Favaro, E. Bernardinello, L. Cavalletto, I. Mezzocolli, S. Luise, S. De Carlo, D. Sacerdoti, A. Gatta, L. Chemello
Journal: Journal of Hepatology (2003)
Letting vegetative patients die.
Authors: A. Fergusson
Journal: BMJ (1992)

tantalisingly useful literature not readily available in any British library, from such titles as the Indiaii ]ooroal of Oplhthalniology or J7ounmal of tze Teoenessee Medical Associatioo.Photocopying?Marvellous invention!Never has so much been copied by so many but, I suggest, used by so few.Beware the siege mentality that requires a copy when, previously, reading, digest- ing, and a few notes would have sufficed.Copyright?Hideous piece of legislation, but, sadly, ours was the lone voice against it as it went through parliament and we are left with the unenviable task of making its impracticalities work.As for licences, Drife is presumably referring to higher education: negotiations between the
Acute urticaria due to alcohol
Authors: A.D. ORMEROD, P.J.A. HOLT
Journal: British Journal of Dermatology (1983)

Journal Article Acute urticaria due to alcohol Get access A.D. ORMEROD, A.D. ORMEROD Department of Dermatology, University Hospital of Wales, Heath Park, Cardiff CF44XW Search for other works by this author on: Oxford Academic Google Scholar P.J.A. HOLT P.J.A. HOLT Department of Dermatology, University Hospital of Wales, Heath Park, Cardiff CF44XW Correspondent: Dr P.J.A. Holt, Department of Dermatology, University Hospital of Wales, Health Park, Cardiff CF44XW. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 108, Issue 6, 1 June 1983, Pages 723–724, https://doi.org/10.1111/j.1365-2133.1983.tb01086.x Published: 01 June 1983 Article history Accepted: 13 October 1982 Published: 01 June 1983
Viral hepatitis. Immunoglobulin response during the course of the disease
Authors: J. P. Giles
Journal: JAMA (1969)

The serum immunoglobulin response was studied in 30 children with infectious hepatitis, MS-1 type and in 28 children with infectious hepatitis, MS-2 type. MS-1 is typical infectious hepatitis (IH) and MS-2 resembles serum hepatitis (SH). IgG, IgM, and IgA levels were determined during the incubation period and acute and convalescent phases of the disease. Infectious hepatitis was characterized by a high increase in IgM levels occurring three to four days after the first evidence of abnormal serum glutamic oxaloacetic transaminase (SGOT) activity. The elevated IgM levels returned to normal 5 to 35 days later. In contrast, SH was usually characterized by only slightly elevated to normal IgM levels during the acute stage of the disease. These studies indicate that the results of serial determinations of immunoglobulin levels performed in conjunction with serial SGOT and thymol turbidity determinations should provide useful data for the differentiation of IH from SH.
Deficiencies in STAT3 Signaling Confers Resistance to Histamine/PAF Induced Vascular Permeability in Autosomal Dominant-Hyper IgE Syndrome (AD-HIES)
Authors: Michael P. O'Connell, Valerie Hox, Celeste Nelson, Thomas DiMaggio, Nina Jones, Paul Sackstein, Alexandra F. Freeman, Ana Olivera, Dean D. Metcalfe, Joshua D. Milner
Journal: Journal of Allergy and Clinical Immunology (2015)
Soluble Fc gamma receptor III (CD 16) and eicosanoid concentrations in gut lavage fluid from patients with inflammatory bowel disease: reflection of mucosal inflammation.
Authors: D W Hommes, J Meenan, M de Haas, F J ten Kate, A E von dem Borne, G N Tytgat, S J van Deventer
Journal: Gut (1996)

Activated neutrophils cause tissue injury in inflammatory bowel disease (IBD). Upon activation, they shed soluble Fc gamma IIIb receptors (sFc gamma RIIIb). The subsequent inflammatory response is modulated by several mediators, including neutrophil derived leukotriene B4 (LTB4), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2). The aim of this study was to determine the value of gut lavage sFc gamma RIII and eicosanoid measurements for the assessment of mucosal inflammation in IBD.A total of 18 patients with active IBD, 10 ulcerative colitis (UC), and eight Crohn's disease (CD), and 12 control patients underwent whole gut lavage. Disease activity, endoscopic appearance, and histopathology were graded. Samples were processed for the determination of sFc gamma RIIIb, LTB4, PGE2, and TXB2.Soluble Fc gamma RIIIb concentrations were increased in both IBD groups. Significant correlations were seen between sFc gamma RIIIb and LTB4 values with histology scores. Mean eicosanoid lavage fluid concentrations in control patients were 14.1 pg/ml for LTB4, 5.6 pg/ml for PGE2, and 397 pg/ml for TXB2. Concentrations of all eicosanoids in IBD patients were significantly increased: LTB4 in UC: mean 73.2 pg/ml, in CD: 96.4 pg/ml (both p < 0.01 v controls). PGE2 in UC: 20.2 pg/ml, in CD: 43.4 pg/ml (p < 0.01). TXB2 in UC: 719.3 pg/ml, in CD: 180.6 pg/ml (both p < 0.05).Whole gut lavage fluid analysis is an effective method to study mucosal eicosanoid production. Soluble Fc gamma RIIIb concentrations in gut lavage fluid closely correlate with histological signs of mucosal inflammation and with lavage LTB4 concentration. These data suggest that lavage Fc gamma RIIIb assessment may be used as a simple assay to estimate mucosal neutrophil infiltration in IBD.
Abstract A38: Human kinase screen for breast cancer oncogenes
Authors: Yashaswi Shrestha, Eric J. Schafer, Barbara Weir, Jesse Boehm, Sapana Thomas, William C. Hahn
Journal: Cancer Research (2009)

Abstract The heterogeneity of breast cancer requires identification of novel genes that promote breast tumor development. Targeting such oncogenes therapeutically promises to improve clinical outcomes. We conducted an in vitro screen to identify human kinases that promote anchorage-independent growth of immortalized human mammary epithelial cells. The screen is based on a transformation model that requires cooperative activation of the PI3K/AKT and MEK/ERK pathways. The pooled screen identified three transforming kinases - PTK6, PAK1 and CAMK4. The functions of these candidates in the PI3K/AKT and/or MEK/ERK pathways are being currently studied to determine their role in breast tumorigenesis. Citation Information: Cancer Res 2009;69(23 Suppl):A38.
How Are Women Sicker than Men?
Authors: Roberta J. Apfel
Journal: Psychotherapy and Psychosomatics (1982)

An overview is presented of psychosomatic problems in women – the epidemiology, physiology and psychology. Surveys of sickness rates in women and psychological studies are used as a basis of speculation about higher female morbidity rates. Theories of psychosomatic illness, the somatic concomitants of hysteria and alexithymia are reviewed as they pertain to observations of gender differences in disease phenomena. A clinical case is presented of thyrotoxicosis, one of the illnesses predominantly found in women.
1005-79 Serial 1 H NMR Spectroscopic Detection of Myocardial Lipid Accumulation Following Brief Coronary Ischemia and Elevation of Serum Lipids in Dogs
Authors: James A. Balschi, David D. Ku, Ingrid Straeter-Knowlen, Jenny Hai, Paul Wolkowicz, William T. Evanochko, Jan den Hollander, James B. Caulfield, Gerald M. Pohost
Journal: Journal of the American College of Cardiology (1995)
Cerebral Perfusion Changes in Hemiplegic Migraine
Authors: Mei-Fang Cheng, Yen-Wen Wu, Sung-Chun Tang
Journal: Clinical Nuclear Medicine (2010)

A 35-year-old man presented with reversible right-sided weakness and impaired verbal expression, followed by a pulsatile headache. Similar yearly attacks had occurred. Abnormally increased Tc-99m ethyl cysteinate dimer (ECD) activity in the left parieto-occipital region was noted during the phase of headache and normalized in the follow-up study. Ten months later, he had 2 episodes of left-sided numbness and headache. Tc-99m ECD during the aura phase revealed hypoperfusion at the right thalamus. Family history and genetic studies were negative, so sporadic hemiplegic migraine was concluded. Our report clearly demonstrated that Tc-99m ECD SPECT is an accurate assessment of brain perfusion changes in hemiplegic migraine.
A "missed" cryoglobulin: the importance of in vitro calcium concentration
Authors: M. ANDRE
Journal: Annals of the Rheumatic Diseases (2000)

How should we manage fibromyalgia?We read with interest your leader, "How should we manage fibromyalgia?". 1 We were puzzled by Paul Reilly's statement that a comprehensive pain management programme...has the best chances of success, although even rheumatologists can practise amateur cognitive behavioural therapy in the clinic".Is Dr Reilly really suggesting that a rheumatologist's amateur eVorts oVer the best outcome for people with fibromyalgia?Dr Reilly oVers no evidence to support this statement.He does, however, find evidence to raise questions as to the value of patient self help groups.Dr Reilly cites a 1992 paper that reports an association between membership of such a group and worse prognosis in chronic fatigue syndrome. 2As the authors emphasised the caution with which the results should be interpreted, it is surprising that Dr Reilly has used this evidence to inform his clinical practice.Firstly, this is ancient research.Things have moved on.Although we would agree that some so called self help groups can end up as a circular review of symptoms, self management courses, which we at Arthritis Care espouse, are a very diVerent matter.Challenging Arthritis is a self management programme-and that title was chosen very deliberately.It is run by people with arthritis for people with arthritis.It gives people the skills to take control of their lives and their arthritis.It is practical and positive, and it works.The eVectiveness of similar programmes in the USA is well recorded. 3 Experience in the United Kingdom shows similar results, including better understanding of symptoms, improved communication with medical staV, and increased use of exercise and relaxation techniques.Probably most importantly of all, self management programmes significantly decrease pain, fatigue, and anxiety. 4 So it is extremely important to diVerentiate between navel gazing self help systems and courses such as ours, which encourage people to take control for themselves-and which work.Similar courses run on the Challenging Arthritis model are now available to people with other chronic conditions.Given Dr Reilly's desire to disabuse patients of the notion that their fibromyalgia is his problem alone, shouldn't eVective courses which encourage people to take control for themselves be a welcome adjunct to his treatment, even if it is run by a patient self management group?ROBINA
Interferon — Its Hour Come at Last?
Authors: Martin S. Hirsch
Journal: New England Journal of Medicine (1978)

Twenty-one years after the discovery of interferon,1 Merigan et al., in this issue of the Journal, provide convincing evidence for its effectiveness in man. In well controlled double-blind trials, leukocyte interferon reduced dissemination of cutaneous herpes zoster in patients with cancer. Interferon-treated patients also had fewer visceral complications and less post-herpetic neuralgia than placebo-treated controls. These observations raise two inter-related questions: Why has it taken so long for human interferon efficacy to be demonstrated, and what are the prospects for its future use?Although interferon's effectiveness in animal-model virus infections has been well established, shortages of human interferon have . . .
Coagulase-Negative Staphylococcal Bacteremia in the Changing Neonatal Intensive Care Unit Population
Authors: Jonathan Freeman
Journal: JAMA (1987)

A fivefold increase in the number of cases of nosocomial coagulase-negative staphylococcal bacteremia was investigated in a neonatal intensive care unit between 1975 and 1982. This apparent outbreak was not the result of increased isolation of coagulase-negative staphylococci from blood cultures nor an increased frequency with which blood cultures were obtained. Rather, it was attributable to a dramatic increase in the overall probability that a positive blood culture would be interpreted as "bacteremia" as opposed to a contaminant by both physicians and infection control staff. Specifically, there had been a 62.3% increase in neonatal intensive care unit bed use by very-low-birth-weight (less than 1000-g) infants between 1975 and 1982, and in both years, positive blood cultures were 3.8 times as likely to be perceived as clinically significant if obtained from such tiny infants. The growing number of very-low-birth-weight babies occupying neonatal intensive care unit beds, coupled with the observation that blood cultures positive for coagulase-negative staphylococci are almost four times as likely to be perceived as clinically significant if obtained from extremely premature infants, may account for the reported increase in nosocomial coagulase-negative staphylococcal bacteremia.
LEFT VENTRICULAR GLOBAL LONGITUDINAL STRAIN INDEPENDENTLY PREDICTS MORTALITY IN PATIENTS WITH MODERATE TO SEVERE WITH PRESERVED LEFT VENTRICULAR EJECTION FRACTION
Authors: Kenya Kusunose, Andrew Goodman, Roosha Parikh, Tylor Barr, Shikhar Agarwal, Zoran Popovic, Richard Grimm, Brian Griffin, Milind Desai
Journal: Journal of the American College of Cardiology (2014)
Listerial Prosthetic Valve Endocarditis
Authors: Louis D. Saravolatz
Journal: JAMA (1978)

LISTERIA monocytogenes endocarditis is an extremely rare entity with, to our knowledge, only 13 cases reported since 1955.<sup>1,2</sup>Unlike other cases of listeriosis, endocarditis caused by this organism does not preferentially occur in immunosuppressed patients. To our knowledge, this communication describes the first successfully treated case of<i>L monocytogenes</i>endocarditis involving a prosthetic heart valve. Also presented are in vitro studies showing synergy with penicillin G potassium and tobramycin sulfate and with other antibiotics that might be useful in the penicillin-allergic patient. Such treatment programs may show greater bactericidal activity and less toxic reaction than those using older aminoglycosides, ie, kanamycin sulfate or streptomycin sulfate. <h3>Materials and Methods</h3> The blood culture isolates were identified as<i>L monocytogenes</i>since they were catalase-positive, pleomorphic, nonsporing Gram-positive rods. They exhibited a characteristic end-over-end tumbling motility at 20 to 25 °C and a narrow ring of β-hemolysis on blood agar. The minimal inhibitory