tbuckley/cabot-search huggingface dataset:
Improving Hospital Design
Authors: P Dormer
Journal: BMJ (1994)

Iden Wickings King's Fund, £19.90, pp 76 ISBN 1–85551–072–3

We all want to live on Quality Street. Accessibility, privacy, confidentiality, dignity, choice, comfort, and security are the contemporary objectives in all services, especially health. And now that we take for granted the raw sufficiency of service that technology offers we are ready to trade up to health care that looks bespoke.

Allegedly people dislike the hospitals of the 1960s and 1970s because the service they provide appears - inhospitable. In an effort to put the tenderness into health technology the King's Fund has commissioned research into hospital design. In 1993 it ran a “best new hospital competition,” which was won by the private Wellington Hospital, in St John's Wood, London. Outside, the Wellington is the architectural equivalent …
Effective Exon Skipping and Restoration of Dystrophin Expression by Peptide Nucleic Acid Antisense Oligonucleotides in mdx Mice
Authors: Haifang Yin, Qilong Lu, Matthew Wood
Journal: Molecular Therapy (2007)

Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy, arising from mutations in the dystrophin gene that preclude the synthesis of functional protein. Antisense oligonucleotides (AOs) have been shown to induce specific exon skipping and thereby restore the reading frame and expression of functional dystrophin. In this report, we examine the effects of peptide nucleic acid (PNA) oligonucleotides and PNAs conjugated with peptides including TAT, muscle-specific peptide (MSP), adeno-associated virus 6 (AAV6) functional domain (AAV6), and AAV8 functional domain (AAV8), on exon skipping in vitro and in vivo. Efficient skipping of targeted exon 23 was achieved in cultured mdx myoblasts with PNA and PNA–peptide conjugates. Furthermore, single intramuscular injections of PNA and all PNA–peptide conjugates resulted in significant numbers of dystrophin-positive fibers in the injected tibialis anterior (TA) muscles of mdx mice, with no apparent local toxicity. Similar effects of exon skipping and dystrophin expression were obtained in mice of all ages. PNA and PNA-AAV6, PNA-AAV8 conjugates induced dystrophin expression in a dose-dependent manner. Our results demonstrate that PNAs have a higher efficiency of exon skipping than 2′O methyl phosphorothioate AOs do, and have a potential use in AO chemistry for antisense therapy of DMD. Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy, arising from mutations in the dystrophin gene that preclude the synthesis of functional protein. Antisense oligonucleotides (AOs) have been shown to induce specific exon skipping and thereby restore the reading frame and expression of functional dystrophin. In this report, we examine the effects of peptide nucleic acid (PNA) oligonucleotides and PNAs conjugated with peptides including TAT, muscle-specific peptide (MSP), adeno-associated virus 6 (AAV6) functional domain (AAV6), and AAV8 functional domain (AAV8), on exon skipping in vitro and in vivo. Efficient skipping of targeted exon 23 was achieved in cultured mdx myoblasts with PNA and PNA–peptide conjugates. Furthermore, single intramuscular injections of PNA and all PNA–peptide conjugates resulted in significant numbers of dystrophin-positive fibers in the injected tibialis anterior (TA) muscles of mdx mice, with no apparent local toxicity. Similar effects of exon skipping and dystrophin expression were obtained in mice of all ages. PNA and PNA-AAV6, PNA-AAV8 conjugates induced dystrophin expression in a dose-dependent manner. Our results demonstrate that PNAs have a higher efficiency of exon skipping than 2′O methyl phosphorothioate AOs do, and have a potential use in AO chemistry for antisense therapy of DMD.
483 Final analysis of virological outcomes and resistance during 5 years of adefovir dipivoxil monotherapy in HBeAg-negative patients
Authors: K. Borroto-Esoda, S. Arterburn, A. Snow, S. Chuck, S. Hadziyannis, S. Locamini, E. Zoulim, J.-M. Pawlotsky
Journal: Journal of Hepatology (2006)
The usefulness of skin tests to prove drug hypersensitivity
Authors: K. Lammintausta, O. Kortekangas-Savolainen
Journal: British Journal of Dermatology (2005)

Suspected drug hypersensitivity is common. Only a minority of cutaneous adverse drug reactions (CADRs) are allergic in origin and will reappear after the next exposure. Methods to confirm suspected CADRs are needed and skin testing could serve as one possibility.To analyse the usefulness of skin tests in revealing drug allergy. The relevance of skin test results was evaluated with drug provocation studies.During 1989-2001, 947 patients with a history of suspected CADR were examined with skin tests including patch tests (PTs) (826 patients), skin prick tests (SPTs) (935 patients) and photopatch tests (12 patients). The occurrence of positive and negative test reactions to different drugs was correlated with clinical history. Drug provocation was carried out in 246 patients.Antimicrobial drugs were suspected and tested most often. A positive PT reaction to one or more drug was seen in 89 of 826 (10.8%), most often to beta-lactams, clindamycin and trimethoprim. A positive SPT reaction was seen in 10 of 935 (1.1%) patients. Challenge was carried out in 17 patients with positive skin test results. Thirteen of 16 (81.2%) PT positives developed exanthema, three remained negative and one SPT-positive patient developed urticaria. Among skin test negatives, 207 of 229 (90.4%) challenges were negative and 22 of 229 (9.6%) were positive, 12 with exanthema, three with fixed drug eruptions and seven with urticaria.Skin testing, especially the PT, was a useful screening method to find a cause of CADR if the reaction was exanthema and if antimicrobial, cardiovascular or antiepileptic drugs were suspected. The SPT detected occasional positives with antimicrobials. In cases of fixed drug eruption, PTs performed at the earlier reaction site were useful. When skin tests are negative or dubious, oral challenge should be carried out to confirm the association.
Mechanical Strain Induces Monocyte Chemotactic Protein-1 Gene Expression in Endothelial Cells
Authors: Danny Ling Wang, Being-Sun Wung, Yeun-Jund Shyy, Cheng-Fu Lin, Yuh-Jen Chao, Shunichi Usami, Shu Chien
Journal: Circulation Research (1995)

Monocyte chemotactic protein-1 (MCP-1), a potent monocyte chemoattractant secreted by endothelial cells (ECs), is believed to play a key role in the early events of atherogenesis. Since vascular ECs are constantly subjected to mechanical stresses, we examined how cyclic strain affects the expression of the MCP-1 gene in human ECs grown on a flexible membrane base deformed by sinusoidal negative pressure (peak level, -16 kPa at 60 cycles per minute). Northern blot analysis demonstrated that the MCP-1 mRNA levels in ECs subjected to strain for 1, 5, or 24 hours were double those in control ECs (P < .05). This strain-induced increase was mainly serum independent, and MCP-1 mRNA level returned to its control basal level 3 hours after release of strain. Culture media from strained ECs contained approximately twice the MCP-1 concentration and more than twice the monocyte chemotactic activity of media from control ECs (P < .05). Pretreatment of collected media with anti-MCP-1 antibody suppressed such activity. Monocyte adhesion to ECs subjected to strain for 12 hours was 1.8-fold greater than adhesion to unstrained control ECs (P < .05). A protein kinase C inhibitor, calphostin C, abolished the strain-induced MCP-1 gene expression. In addition, cAMP- or cGMP-dependent protein kinase inhibitors (KT5720 and KT5823, respectively) partially inhibited such expression. Pretreatment with EGTA or the intracellular Ca2+ chelator BAPTA/AM strongly suppressed the strain-induced MCP-1 mRNA. Verapamil, a Ca2+ channel blocker, greatly reduced MCP-1 mRNA levels in both strained and unstrained ECs.(ABSTRACT TRUNCATED AT 250 WORDS)
Pacifier Use, Early Weaning, and Cry/Fuss Behavior
Authors: Michael S. Kramer
Journal: JAMA (2001)

for a very long time.Small clay pacifiers have been found in Cypriot graves dating back to about 1000 BC, and breast-shaped pottery nipples have been recovered from Roman graves dating from around AD 100. 1,2In the early 1900s, however, pacifiers began to be condemned by the infant welfare movement.Various reformers referred to the pacifier as a product of "perverted American ingenuity," 3 an "instrument of torture," 4 and a "curse of babyhood." 5More recently, clinicians and public health practitioners have raised concerns that the pacifier causes "nipple confusion" and thereby leads to early weaning. 6In fact, avoidance of pacifiers constitutes step 9 of the World Health Organization/United Nations Children's Fund Baby-Friendly Hospital Initiative. 7hat is the evidence of actual benefit or harm associated with pacifier use?Several observational studies published since the Baby-Friendly Hospital Initiative was developed, including studies from Brazil, 8-10 Sweden, 11,12 England, 13,14 New Zealand, 15 and the
CpG Methylation of a Plasmid Vector Results in Extended Transgene Product Expression by Circumventing Induction of Immune Responses
Authors: A. Reyes-Sandoval, H.C.J. Ertl
Journal: Molecular Therapy (2004)

Gene therapy has the potential to cure inherited diseases if the delivered genes achieve long-term expression at therapeutic levels in the targeted tissues. Expression is commonly short-lived due to induction of cell-mediated immune responses to the gene therapy vehicle and/or the transgene product, which can be perceived as "foreign" by the host's immune system. Plasmid expression vectors have been used to deliver genes. Bacterial DNA carries immunostimulatory sequences in the form of unmethylated CpG motifs, which induce an inflammatory reaction that in turn promotes activation of transgene product-specific B and T cells. Elimination or methylation of immunostimulatory CpG sequences in plasmid expression vectors prevents the stimulation of transgene product-specific immune responses without necessarily reducing transgene expression. In this study, we tested if a CpG-methylated plasmid expression vector expressing the highly immunogenic glycoprotein of rabies virus can achieve prolonged transgene product expression by circumventing immune recognition. Our data show that mice inoculated with a CpG-methylated plasmid expression vector show delayed clearance of transfected cells and fail to mount a strong immune response to the transgene product. Gene transfer with a CpG-methylated plasmid results in a state of immunological low responsiveness to the transgene product, which may facilitate readministration of the transgene. Nevertheless, mice remain responsive to the transgene product delivered by a viral vector.
Blood Cell Aggregation and Screen Filtration Pressure
Authors: ROY L. SWANK, ELI DAVIS
Journal: Circulation (1966)

Changes in the microcirculation of the conjunctiva were compared with the screen filtration pressure (SFP) of venous blood in presumed normal subjects and in others with known systemic disease. The presence of arteriolar aggregation and of other circulatory abnormalities was not attended by significantly different mean SFP values. When, however, 2.5 µg of adenosine diphosphate (ADP) per milliliter were added to blood in vitro 20 to 30 seconds before the SFP determination, the SFP increased. In subjects with normal microcirculation, the increase was slight; in those with abnormal circulation, it was marked. When abnormal changes in the circulation were present, or ADP potentiation was high, there was an increase in the spread of control SFP values. Also when the ADP potentiation was high, the control SFP values were slightly higher than when the SFP potentiation was low. Two serotonin antagonists did not prevent or decrease the increase in SFP by ADP.
The role of protein phosphatases in the expression of inducible nitric oxide synthase in the rat hepatocyte
Authors: Bradley S. Taylor, Shubing Liu, Raphael T. Villavicencio, Raymond W. Ganster, David A. Geller
Journal: Hepatology (1999)

Previously, we demonstrated that nuclear factor–κB (NF–κB) mediates cytokine–induced hepatic inducible nitric oxide synthase (iNOS) expression. NF–κB activation is regulated by kinases and phosphatases whose function is only beginning to be understood. Therefore, experiments were performed to determine the role of protein phosphatases (PPase) in cytokine–induced iNOS expression. Hepatocytes were stimulated with cytokines in the presence or absence of tyrosine phosphatase inhibitors (pervanadate [PV], phenylarsine oxide [PAO]) and a serine–threonine phosphatase inhibitor (okadaic acid [OA]). Cytokines induced hepatocyte iNOS mRNA, protein, and NO 2 - production that was substantially decreased by the addition of the tyrosine phosphatase inhibitors (PAO and PV). The serine–threonine phosphatase inhibitor (OA) decreased NO release and protein levels in a concentration–dependent fashion; however, iNOS mRNA levels were not significantly reduced. Nuclear run–on experiments demonstrated that protein tyrosine phosphatases (PTPases) are required for iNOS transcription, while the serine–threonine phosphatase inhibitor (OA) had no effect on iNOS transcription. Electromobility shift assays (EMSAs) revealed that the tyrosine–phosphatase inhibitors blocked cytokine–induced NF–κB activation, while OA did not have a significant effect on NF–κB DNA binding activity. Therefore, tyrosine phosphatases are involved in the regulation of cytokine–induced activation of NF–κB, while serine–threonine phosphatases posttranscriptionally regulate iNOS translation. These results identify the regulatory role of specific protein phosphatases (PPases) in hepatic iNOS expression
Short-term synchronized retroperfusion before reperfusion reduces infarct size after prolonged ischemia in dogs.
Authors: Y Wakida, R Nordlander, S Kobayashi, S Kar, R Haendchen, E Corday
Journal: Circulation (1993)

BACKGROUND Previous studies have demonstrated that synchronized coronary venous retroperfusion (SRP) can restore blood flow to the ischemic myocardium, resulting in infarct size reduction and improvement of the left ventricular function. Despite the nutritive blood flow achieved by SRP being relatively limited, SRP has been shown to improve washout of by-products from the ischemic myocardium. The aim of this study was to investigate whether short-term SRP immediately prior to reperfusion would attenuate the deteriorative phenomena following reperfusion. METHODS AND RESULTS Closed-chest anesthetized dogs underwent 3 hours of left anterior descending coronary artery (LAD) occlusion. The dogs were then randomized into two groups: (1) control group (n = 9), in which the occlusion was immediately followed by 3-hour reperfusion; or (2) SRP group (n = 9), in which SRP was started 3 hours after occlusion and maintained for 30 minutes with sustained occlusion followed by 2.5-hour reperfusion with simultaneous discontinuation of SRP. There were no statistical differences between the groups in global hemodynamics and degree of ischemia measured by radiolabeled microspheres. Myocardial infarct size (triphenyltetrazolium method) expressed as percentage of risk area was significantly smaller in the SRP group (24 +/- 7%, mean +/- SEM) than in the control group (54 +/- 9%). The extent of myocardial hemorrhage expressed as percentage of infarct size was also significantly reduced in the SRP group (3 +/- 2%) compared with the control group (24 +/- 6%). The increase in end-diastolic wall thickness in the ischemic area after reperfusion assessed by two-dimensional echocardiography was significantly less in the SRP group. Blood flow measurements after reperfusion demonstrated the occurrence of no-reflow phenomenon only in the control group. Histological examination revealed extensive myocardial hemorrhages only in the control group, which extended into the nonnecrotic myocardium in four of nine hearts and extensive contraction band necrosis compared with the SRP group. CONCLUSIONS Short-term SRP prior to reperfusion can reduce infarct size, myocardial hemorrhage, wall swelling, and no-reflow phenomenon. The mechanism of this beneficial effect is not clear but might be due to gradual reperfusion and washout of by-products from the ischemic myocardium before fully oxygenated arterial blood reperfusion.
What Are the Public Health Effects of Direct-to-Consumer Drug Advertising?
Authors: Elizabeth A Almasi, Randall S Stafford, Richard L Kravitz, Peter R Mansfield
Journal: PLoS Medicine (2006)

Background to the Debate Only two industrialized countries, the United States and New Zealand, allow direct-to-consumer advertising (DTCA) of prescription medicines, although New Zealand is planning a ban [1]. The challenge for these governments is ensuring that DTCA is more beneficial than harmful. Proponents of DTCA argue that it helps to inform the public about available treatments and stimulates appropriate use of drugs for high-priority illnesses (such as statin use in people with ischemic heart disease). Critics argue that the information in the adverts is often biased and misleading, and that DTCA raises prescribing costs without net evidence of health benefits.
TH-17-Associated Cytokines in Atopic Dermatitis
Authors: O. Roshdy, D. Prefontaine, F. Chouiali, A. Vazquez-Tello, M. Boguniewicz, M. Howell, R. He, R.S. Geha, D.Y. Leung, Q. Hamid
Journal: Journal of Allergy and Clinical Immunology (2009)
Demonstration of pre-S polypeptides of hepatitis B virus in infected livers
Authors: Swan N. Thung, Michael A. Gerber, Efthimios J. Kasambalides, Bal K. Gilja, William Keh, Wolfram H. Gerlich
Journal: Hepatology (1986)

The large (pre-S1), middle (pre-S2) and major (P24) polypeptides of HBsAg have been defined in detail, but their role in hepatitis B virus infection is not known. Therefore, we studied the expression of pre-S1, pre-S2 and P24 in the liver of 15 patients with acute or chronic hepatitis B virus infection using monoclonal and polyclonal antibodies in a double staining immunofluorescence method. The pre-S and major HBsAg polypeptides were co-expressed in the hepatocyte cytoplasm of all patients except for one case of chronic active hepatitis and cirrhosis. HBcAg was present in hepatocyte nuclei of nine patients suggestive of active hepatitis B virus replication. These studies support the hypothesis that the pre-S polypeptides represent essential components of the envelope of hepatitis B virus.
Points: Confidentiality of medical records
Authors: O Troughton
Journal: BMJ (1978)

IL-23 is required for the IL-17 response to infection with <i>Mycobacterium tuberculosis</i>, but is not required for the early control of bacterial growth. However, mice deficient for the p19 component of IL-23 (<i>Il23a</i><sup>−/−</sup>) exhibit increased bacterial growth late in infection that is temporally associated with smaller B cell follicles in the lungs. Cxcl13 is required for B cell follicle formation and immunity during tuberculosis. The absence of IL-23 results in decreased expression of Cxcl13 within <i>M. tuberculosis</i>-induced lymphocyte follicles in the lungs, and this deficiency was associated with increased cuffing of T cells around the vessels in the lungs of these mice. <i>Il23a</i><sup>−/−</sup> mice also poorly expressed IL-17A and IL-22 mRNA. These cytokines were able to induce Cxcl13 in mouse primary lung fibroblasts, suggesting that these cytokines are likely involved in B cell follicle formation. Indeed, IL-17RA–deficient mice generated smaller B cell follicles early in the response, whereas IL-22–deficient mice had smaller B cell follicles at an intermediate time postinfection; however, only <i>Il23a</i><sup>−/−</sup> mice had a sustained deficiency in B cell follicle formation and reduced immunity. We propose that in the absence of IL-23, expression of long-term immunity to tuberculosis is compromised due to reduced expression of Cxcl13 in B cell follicles and reduced ability of T cells to migrate from the vessels and into the lesion. Further, although IL-17 and IL-22 can both contribute to Cxcl13 production and B cell follicle formation, it is IL-23 that is critical in this regard.
Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy
Authors: Haiyan Jiang, Linda B. Couto, Susannah Patarroyo-White, Tongyao Liu, Dea Nagy, Joseph A. Vargas, Shangzhen Zhou, Ciaran D. Scallan, Jurg Sommer, Sharmila Vijay, Federico Mingozzi, Katherine A. High, Glenn F. Pierce
Journal: Blood (2006)
Enhanced inositol trisphosphate response to alpha 1-adrenergic stimulation in cardiac myocytes exposed to hypoxia.
Authors: G P Heathers, A S Evers, P B Corr
Journal: Journal of Clinical Investigation (1989)

Myocardial ischemia elicits an enhanced responsivity to alpha 1-adrenergic stimulation and a reversible increase in alpha 1-adrenergic receptor number. In adult cardiac myocytes, alpha 1-adrenergic receptor number increases two- to threefold after 10 min of hypoxia, an increase similar to that seen during ischemia in vivo. To determine whether this increase in alpha 1-adrenergic receptor number leads to an enhanced synthesis of inositol trisphosphate, the intracellular second messenger for the alpha 1-adrenergic receptor, the mass of inositol trisphosphate was quantified by a novel procedure developed in our laboratory that circumvents problems associated with using labeled precursors. The peak increases in inositol trisphosphate levels of three- to fourfold were measured after 30 s of norepinephrine stimulation and exhibited a 50% effective concentration (EC50) of 7.9 x 10(-8) M. Hypoxia produced a marked leftward shift in the dose-response curve for the production of inositol trisphosphate in response to norepinephrine stimulation (EC50 = 1.2 x 10(-8) M). Hypoxia also induced a 100-fold reduction in the concentration of norepinephrine required to elicit a threshold increase in inositol trisphosphate (10(-9) M), compared with control normoxic myocytes (10(-7) M). Thus, hypoxia, which increases alpha 1-adrenergic receptor density, also leads to an enhanced production of inositol trisphosphate and could account for the enhanced alpha 1-adrenergic responsivity in the ischemic heart in vivo, which is known to facilitate arrhythmogenesis.
DISCORDANCE IN LEFT ATRIAL VOLUME MEASUREMENTS BY TRANSTHORACIC ECHOCARDIOGRAPHY VERSUS CMRI IN PATIENTS WITH AND WITHOUT HEART FAILURE
Authors: Nowell Mark Fine, Danielle Henkel, Sang-Chol Lee, Sung-A Chang, Brian Shapiro, James Glockner, Philip Araoz, Jin-Oh Choi, Yeon Hyeon Choe, Wayne Miller, Jae Oh
Journal: Journal of the American College of Cardiology (2013)
Mitotane. Spironolactone antagonism in Cushing's syndrome
Authors: J. Wortsman
Journal: JAMA (1977)

CUSHING'S syndrome is usually treated surgically when it is associated with pituitary-dependent adrenocortical hyperplasia or an adrenal adenoma. However, the patient's general condition may exclude a surgical approach, and in these cases as well as in certain instances of Cushing's syndrome due to metastatic adrenal carcinoma of ectopic adrenocorticotropic hormone (ACTH) production, medical treatment has a place. The drugs available include mitotane, aminoglutethimide, and metyrapone; more recently, successful treatment of adrenocortical hyperplasia with cyproheptadine hydrochloride has been reported. Mitotane and aminoglutethimide have been the most commonly used, but both have a high incidence of adverse reactions.<sup>1</sup>Only mitotane leads to permanent destruction of the adrenal cortex. Spironolactone is commonly used in the management of the hypokalemia of Cushing's syndrome, but in the case we are presenting, it is suggested that this drug blocks the action of mitotane. <h3>Report of a Case</h3> A 65-year-old woman with features of florid Cushing's