tbuckley/cabot-search huggingface dataset:
Oral methoxsalen photochemotherapy of recalcitrant dermatoses of the palms and soles
Authors: WARWICK L. MORISON, JOHN A. PARRISH, THOMAS B. FITZPATRICK
Journal: British Journal of Dermatology (1978)

PUVA therapy successfully cleared various dermatoses mainly confined to the palms and soles in 18 of 20 patients treated. The conditions treated were: plaque-type psoriasis, pustular psoriasis, endogenous eczema and persistent palmoplantar pustulosis. Seventeen patients were treated in a controlled study of PUVA therapy versus no treatment at all and in 16 of these patients the disease was cleared in the PUVA-treated areas while the untreated areas remained unchanged or deteriorated. Twelve of the 18 patients were maintained in a clear state by continued maintenance PUVA treatment over 6--31 months while 3 patients had a spontaneous remission and are free of disease off all treatment.
Insulin Excites Anorexigenic Proopiomelanocortin Neurons via Activation of Canonical Transient Receptor Potential Channels
Authors: Jian Qiu, Chunguang Zhang, Amanda Borgquist, Casey C Nestor, Arik W. Smith, Martha A. Bosch, Stephen Ku, Edward J. Wagner, Oline K. Rønnekleiv, Martin J. Kelly
Journal: Cell Metabolism (2014)
Platelet Activation With Unfractionated Heparin at Therapeutic Concentrations and Comparisons With a Low-Molecular-Weight Heparin and With a Direct Thrombin Inhibitor
Authors: Zihui Xiao, Pierre Théroux
Journal: Circulation (1998)

Background —The growing use of heparin in acute thrombotic disorders, coupled with the availability of many new antithrombotic agents, emphasizes the need for adequate characterization of the platelet effects of the various anticoagulants. Controversial platelet effects have been reported with heparin (eg, enhanced platelet activation in vitro with high doses and no such effect in vivo at therapeutic doses). This study examined platelet receptor activation and platelet aggregation at therapeutic concentrations of unfractionated heparin (UFH), of enoxaparin, a low-molecular-weight heparin, and of argatroban, a direct thrombin inhibitor. Methods and Results —Platelet P-selectin (CD62) and activated GP IIb/IIIa (PAC-1) expression on platelet membrane was quantified in whole blood as well as platelet aggregation in platelet-rich plasma in 43 patients with unstable angina before and during treatment with UFH or enoxaparin. Studies were also carried out in blood of seven normal volunteers after addition ex vivo of UFH (0.25 U/mL), enoxaparin (0.25 U/mL), argatroban (1 ng/mL), and normal saline. UFH in patients with unstable angina increased the percentage of circulating platelets positive to PAC-1 from 2.7±1.7% to 4.4±3.4% ( P &lt;.05) and to CD62 from 1.6±0.9% to 2.7±1.5% ( P &lt;.01). Platelets were also hyperresponsive to stimulation with ADP and with the thrombin-receptor agonist peptide. Aggregation to ADP increased from 6.8±4.6% to 11.2±7.0% and to TRAP from 5.2±3.5% to 11.1±6.0% ( P &lt;.001). The addition of UFH to blood of normal volunteers resulted also in activation of GP IIb/IIIa receptors, expression of P-selectin, and enhanced platelet aggregation. Enoxaparin had only minor effects on platelet activation in vivo and ex vivo, and argatroban, evaluated ex vivo, had no detectable effects. Conclusions —Therapeutic concentrations of UFH are associated with platelet activation.
Enhancement of cholesteryl ester transfer in plasma by hormone-replacement therapy
Authors: Andreas Ritsch, Susanne Kaser, Birgit Volgger, Elisabeth Abfalter, Wolfgang Sturm, Hannes G[auml ]nzer, Bernhard F[ouml ]ger, Rudolf Kirchmair, Christoph Ebenbichler, Josef R. Patsch
Journal: Metabolism (2002)
Managing perioperative risk in patients undergoing elective non-cardiac surgery
Authors: R. M. Pearse, P. J. E. Holt, M. P. W. Grocott
Journal: BMJ (2011)

#### Summary points

The perioperative care of patients undergoing major surgery is increasingly recognised as an area that substantially affects public health and for which needs are poorly met. Around 15% of people who undergo inpatient surgery are at high risk of complications, such as pneumonia or myocardial infarction, because of age, comorbid disease, or the complexity of the surgical procedure.1 2 High risk surgical patients account for 80% of all perioperative deaths. Non-cardiac surgery is an important cause of death and disability, owing to the high volume of procedures and related adverse outcomes.1 2 3 4 5 6 Around 250 million major surgical procedures are performed worldwide each year.3 This number is increasing as gross domestic product rises in poorer countries.3 Assuming a hospital mortality rate of 1%, non-cardiac surgery will be associated with 2.5 million deaths worldwide each year and complication rates at least five times this figure.1 2 3 4 5 6 Patients who survive postoperative complications commonly experience functional limitations and reduced long term survival.4 5 6

Varying mortality rates between hospitals indicate the potential and the need to improve survival after surgery.7 However, the reasons for the variation in mortality are not fully understood, making effective planning more …
Links between rhinitis and asthma
Authors: J. Bousquet, A. M. Vignola, P. Demoly
Journal: Allergy (2003)

There is compelling evidence of a close relationship between the upper and lower airways in asthma and rhinitis. Rhinitis is present in the majority of patients with asthma, and a significant minority of patients with rhinitis have concomitant asthma. Similarities between the two conditions occur in the nature of the inflammation present in the target tissues. A common initiating step in the inflammatory process of allergic airways disease is the presence of immunoglobulin E providing an adaptor molecule between the offending allergen and inflammatory cell activation and mediator release. Differences in the two conditions arise largely from the structural differences between the nose and the lungs. In an asthmatic, concomitant allergic rhinitis increases healthcare costs and further impairs quality of life. The presence of rhinitis should always be investigated in children and young adults with asthma. Subjects with allergic rhinitis have an increased risk of developing asthma and may form a suitable population for secondary intervention to interrupt the ‘allergic march’.
Selective redox-responsive drug release in tumor cells mediated by chitosan based glycolipid-like nanocarrier
Authors: Ying-wen Hu, Yong-zhong Du, Na Liu, Xuan Liu, Ting-ting Meng, Bo-lin Cheng, Jia-bei He, Jian You, Hong Yuan, Fu-qiang Hu
Journal: Journal of Controlled Release (2015)
Physiological Responses to Intravenous Diazepam as a Sedative for Conservative Dentistry
Authors: T. E. J. Healy, J. S. Robinson, M. D. Vickers
Journal: BMJ (1970)

The physiological responses to intravenous diazepam and oral local analgesia for conservative dentistry have been assessed in 16 patients. Apart from a transient tachycardia during actual administration of the drug, no clinically significant changes occurred in the haemodynamic, respiratory, or metabolic status of the patients. In some patients there was a period of incompetence of the laryngeal closure reflex.
Connexin 43-Enhanced Suicide Gene Therapy Using Herpesviral Vectors
Authors: Peggy Marconi, Masakazu Tamura, Shusuke Moriuchi, David M. Krisky, Ajay Niranjan, William F. Goins, Justus B. Cohen, Joseph C. Glorioso
Journal: Molecular Therapy (2000)

Tumor cell transduction with the herpes simplex virus (HSV) thymidine kinase (tk) gene and treatment with ganciclovir (GCV) is a widely studied cancer gene therapy. Connexin (Cx)-dependent gap junctions between cells facilitate the intercellular spread of TK-activated GCV, thereby creating a bystander effect that improves tumor cell killing. However, tumor cells often have reduced connexin expression, thus thwarting bystander killing and the effectiveness of TK/GCV gene therapy. To improve the effectiveness of this therapy, we compared an HSV vector (TOCX) expressing Cx43 in addition to TK with an isogenic tk vector (TOZ.1) for their abilities to induce bystander killing of Cx-positive U-87 MG human glioblastoma cells and Cx-negative L929 fibrosarcoma cells in vitro and in vivo. The results showed that low-multiplicity infection of U-87 MG cells with TOCX only minimally increased GCV-mediated cell death compared with infection by TOZ.1, consistent with the endogenous level of Cx in these cells. In contrast, bystander killing of L929 cells was markedly enhanced by vector-mediated expression of Cx. In vivo experiments in which U-87 MG cells were preinfected at low multiplicity and injected into the flanks of nude mice showed complete cures of all animals in the TOCX group following GCV treatment, whereas untreated animals uniformly formed fatal tumors. TOCX injection into U-87 MG intradermal and intracranial tumors resulted in prolonged survival of the host animals in a GCV-dependent manner. Together, these results suggest that the combination of TK and Cx may be beneficial for the treatment of human glioblastoma.
Stimulation of lymphokine release from T lymphoblasts. Requirement for mRNA synthesis and inhibition by cyclosporin A.
Authors: A Granelli-Piperno, K Inaba, R M Steinman
Journal: The Journal of Experimental Medicine (1984)

Three-day, concanavalin A-induced T lymphoblasts have been used as a model to study lymphokine release from sensitized T cells. The blasts responded to interleukin 2 (IL-2) but did not constitutively produce this or other lymphokines. After mitogen restimulation, blast cells synthesized IL-2 as well as gamma-interferon, B cell-stimulating factor(s), and cytolytic differentiation factor(s). This production resulted from the induction of biologically active lymphokine mRNA. Cyclosporin A (CSA), a potent immunosuppressive agent, strongly inhibited synthesis of IL-2, gamma-interferon, and B cell- and CTL-stimulating factor(s), from mitogen-restimulated T blasts. In contrast, CSA did not block the cytolytic activity of the T blasts, nor modify bulk protein synthesis induced by Con A. CSA also blocked lymphokine release from a phorbol myristate acetate-stimulated thymoma cell line, EL-4. The effect of CSA was to block the induction of active lymphokine mRNA, as assayed in an oocyte translation system. This selective inhibition of lymphokine mRNA suggests that CSA may be useful in the therapy of inflammatory, lymphokine-mediated disease states.
Adenovirus gene therapy for hypercholesterolemia, thrombosis and restenosis
Authors: Robert D Gerard, Désiré Collen
Journal: Cardiovascular Research (1997)

Time for primary review 28 days.

Human adenoviruses are non-enveloped, icosahedral viruses, approximately 130 nm in diameter. The linear, double-stranded DNA viral genome containing covalently attached terminal protein derived from a unique replication process is almost 36 Kb in length. Although forty nine serotypes of human adenovirus in six serological subgroups have been identified, only serotypes 2 and 5 of subgroup C have been extensively employed as gene transfer vectors.

Recombinant helper-independent adenovirus vectors are easily constructed, analyzed and propagated using standard recombinant DNA and virological techniques (reviewed in [1, 2]). Foreign genes can be inserted into the adenovirus genome in a variety of locations to generate recombinant vectors, although substitution of early region 1 (E1) has been most widely used. Replacement of E1, since it is required for the efficient expression of the remainder of the viral genome, generates a vector which can only be propagated in a complementing cell line which supply the missing E1A functions in trans from an integrated copy of the appropriate fragment of the viral genome. Such E1 replacement vectors are typically propagated in the 293 [3]or 911 [4]cell lines. Recombinant viruses produced in this manner can be stably propagated to a titer of 108–109 plaque forming units per ml and are readily purified free of contaminating viral proteins and empty capsids using CsCl density gradient centrifugation for in vivo use [2].

Recombinant adenoviruses are highly efficient vectors for the transfer of foreign genes into cells both in vitro and in vivo. Because adenovirus vectors can infect a broad range of mammalian cell types, they have become the preferred vector for a wide variety of in vivo applications [5]and are currently approved for use in a limited number of human gene therapy trials. The high efficiency of … 

* Corresponding author. Tel.: +32 16 346182; Fax: +32 16 345990.
P1229 LOW PERSISTENCE OF RESISTANCE-ASSOCIATED VARIANTS AFTER 3 DAYS OF MONOTHERAPY WITH NS5B NNI SITE II INHIBITOR GS-9669 IN GENOTYPE 1 HCV PATIENTS
Authors: H. Dvory-Sobol, V. Gontcharova, R. Martin, E.J. Lawitz, J. McHutchison, E.S. Svarovskaia, M.D. Miller, H. Mo
Journal: Journal of Hepatology (2014)
Doctors asked to brush up on NHS finances to help drive efficiency
Authors: O. Mashta
Journal: BMJ (2009)

<h3>Objective.</h3> Syndecan-1 (SDC-1) is a major constituent of the endothelial glycocalyx, which plays a role in maintaining vascular homeostasis and functions as a glomerular filtration barrier. SDC-1 is readily shed into the blood under various conditions, but the clinical implication of circulating SDC-1 in patients with systemic lupus erythematosus (SLE) remains unclear. We aimed to investigate the association of serum SDC-1 level with certain clinical manifestations of SLE. <h3>Methods.</h3> We measured serum SDC-1 levels by ELISA in 111 patients with SLE, 18 with rheumatoid arthritis (RA), and 20 healthy subjects, and investigated its association with clinical manifestations and laboratory variables. <h3>Results.</h3> Serum SDC-1 levels were higher in patients with SLE than in those with RA and healthy controls (both p &lt; 0.001) and were positively correlated with SLE Disease Activity Index (SLEDAI; r = 0.367, p &lt; 0.001) and anti-dsDNA antibody level (r = 0.259, p = 0.007), but inversely correlated with serum C3 and CH50 levels (r = −0.305, p = 0.001 and r = −0.244, p = 0.012). Patients with active nephritis had higher serum SDC-1 levels than patients with inactive nephritis and those without nephritis (both p &lt; 0.001). In addition, serum SDC-1 levels were correlated with renal SLEDAI score (r = 0.540, p &lt; 0.001) and excretion of proteinuria as measured by spot urine protein/creatinine ratio (r = 0.538, p &lt; 0.001). In 14 patients with lupus nephritis (LN) whose serum samples were obtained at the time of renal biopsy, there was a positive correlation between serum SDC-1 levels and activity index (r = 0.632, p = 0.015). <h3>Conclusion.</h3> Serum SDC-1 levels are increased in SLE patients with nephritis, indicating that SDC-1 might be a useful serum biomarker for active LN.
Lost in translation: trust launches glossary of Yorkshire terms
Authors: R. Wilkins
Journal: BMJ (2010)

Yorkshire based doctors seeking to interpret local phrases need look no further than the Glossary of Yorkshire medical terms , a guide published by NHS Doncaster to help doctors understand why their patients might tell them that “Barnsley’s at home” among other euphemisms.

The glossary—aimed at European doctors but useful for any healthcare staff needing a Yorkshire refresher—contains 138 translations for common ailments and parts of the body.

All of the terms have been used by patients during consultations, and …
Wilson's disease: Changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease
Authors: Valentina Medici, Noreene M. Shibata, Kusum K. Kharbanda, Janine M. LaSalle, Rima Woods, Sarah Liu, Jesse A. Engelberg, Sridevi Devaraj, Natalie J. Török, Joy X. Jiang, Peter J. Havel, Bo Lönnerdal, Kyoungmi Kim, Charles H. Halsted
Journal: Hepatology (2012)

Hepatic methionine metabolism may play an essential role in regulating methylation status and liver injury in Wilson's disease (WD) through the inhibition of S-adenosylhomocysteine hydrolase (SAHH) by copper (Cu) and the consequent accumulation of S-adenosylhomocysteine (SAH). We studied the transcript levels of selected genes related to liver injury, levels of SAHH, SAH, DNA methyltransferases genes (Dnmt1, Dnmt3a, Dnmt3b), and global DNA methylation in the tx-j mouse (tx-j), an animal model of WD. Findings were compared to those in control C3H mice, and in response to Cu chelation by penicillamine (PCA) and dietary supplementation of the methyl donor betaine to modulate inflammatory and methylation status. Transcript levels of selected genes related to endoplasmic reticulum stress, lipid synthesis, and fatty acid oxidation were down-regulated at baseline in tx-j mice, further down-regulated in response to PCA, and showed little to no response to betaine. Hepatic Sahh transcript and protein levels were reduced in tx-j mice with consequent increase of SAH levels. Hepatic Cu accumulation was associated with inflammation, as indicated by histopathology and elevated serum alanine aminotransferase (ALT) and liver tumor necrosis factor alpha (Tnf-α) levels. Dnmt3b was down-regulated in tx-j mice together with global DNA hypomethylation. PCA treatment of tx-j mice reduced Tnf-α and ALT levels, betaine treatment increased S-adenosylmethionine and up-regulated Dnmt3b levels, and both treatments restored global DNA methylation levels.Reduced hepatic Sahh expression was associated with increased liver SAH levels in the tx-j model of WD, with consequent global DNA hypomethylation. Increased global DNA methylation was achieved by reducing inflammation by Cu chelation or by providing methyl groups. We propose that increased SAH levels and inflammation affect widespread epigenetic regulation of gene expression in WD.
The Obese Patient and Anesthesia
Authors: Willis A. Warner
Journal: JAMA (1968)

The obese patient poses special problems when presenting for anesthesia and surgery. A consideration of anesthetic problems related to obesity brings to mind those in several areas: (1) problems related to intravenous therapy; (2) problems referable to securing and maintaining the airway; (3) ventilatory problems, both intraoperatively and postoperatively; (4) difficulty in attaining adequate relaxation and adequate operative conditions; (5) factors influencing the uptake and distribution of anesthetic agents; and (6) anatomic problems encountered with regional anesthesia. In addition (7) frequent accompaniments and sequelae of obesity, eg, hypertension and diabetes mellitus, may alter responses to anesthetic agents and other depressant drugs. Our approach to anesthetic management of the obese patient is necessarily pragmatic, because definitive studies assessing the risks of obesity are lacking. We believe that obese patients have a greater incidence of anesthetic complications; further studies need to be made. Merely starting an intravenous solution may be unnerving to
STUDIES ON IMMUNOLOGICAL RELATIONSHIPS AMONG THE PNEUMOCOCCI
Authors: John Y. Sugg, James M. Neill
Journal: The Journal of Experimental Medicine (1931)

This paper reports inter-reactions of anaphylaxis and precipitation between antigens and antisera derived from the Type II variety of pneumococcus and from one variety of yeast. That the reactions occurred only with Type II and not with Types I and III is proof that the pneumococcus antigen responsible for the anaphylaxis of the antiyeast sensitized animals was the type-specific carbohydrate (S). Pronounced differences in respect to reactivity with the pneumococcus antigen were found between individual antiyeast sera that were of equal potency in respect to reactivity with the yeast antigen. This fact emphasizes the desirability of the use of antisera from a large number of individual animals in the study of microbial inter-relationships.
Increased Cholecystectomy Rate After Introduction of Laparoscopic Cholecystectomy-Reply
Authors: Andrew K. Diehl
Journal: JAMA (1994)

<h3>In Reply.</h3> —Foster et al present statistics suggesting that the number of cholecystectomies performed nationally has changed little in recent years. They argue that the abrupt rise in surgical rates reported by Legorreta et al<sup>1</sup>in Pennsylvania and discussed in my Editorial<sup>2</sup>does not reflect overall US trends. However, published data from the NHDS confirm a recent increase. Total US cholecystectomies rose from 504 000 in 1989 to 571000 in 1991, or 13%. Moreover, in 1991 the age-specific cholecystectomy rates for persons aged 45 to 64 years and 65 years and older were the highest recorded since 1970.<sup>3,4</sup>It appears likely that the recent trends documented in Pennsylvania and Connecticut reflect the national scene.<sup>1,5</sup> The wide variation in per-patient expenditures reported by Drs Klar and Kongstvedt are based on data that may not fully account for differences in clinical presentation. For example, patients suffering acute biliary
Bancroftian Filariasis and Ivermectin
Authors: Peter F. Weller, Leo X. Liu
Journal: New England Journal of Medicine (1990)

Lymphatic filariasis due to infection with Wuchereria bancrofti was introduced into the Americas with the importation of infected African slaves. In the early 1900s, both asymptomatic microfilaremia and the most obvious stigma of lymphatic filariasis, elephantiasis, were present in residents of Charleston, South Carolina.1 Although lymphatic filariasis never became endemic in the United States, filarial diseases remain a major health problem in many areas of the world. More than 90 million people are infected with lymphatic filarial parasites, and more than 900 million people living in areas of endemic infection are at risk.2 Filarial parasites are multicellular helminthic organisms belonging . . .
493 AZATHIOPRINE PRODUCES AUTOPHAGY THROUGH ERK/MTOR/P70S6K PATHWAY IN HEPG2 CELLS
Authors: B. Hernández-Breijo, J. Monserrat, Á. González-Rodríguez, M.D. Fernández-Moreno, I.D. Román, M. Álvarez de Mon, Á.M. Varverde, J.P. Gisbert, L.G. Guijarro
Journal: Journal of Hepatology (2011)
THE MECHANISM OF MAN—ITS EGO AND COSMOS.
Authors: SAMUEL KNOX CRAWFORD
Journal: JAMA (1898)

None but the creative power from which all things sprang can aspire to the construction of something out of nothing, or the reconstruction of an entity into nothing. Chemistry attempts to describe all material substances, to tell of their ultimate particles, and formulate the laws which govern their combinations and decompositions, but does not assume to create or annihilate the molecule with which it deals or the atom which it fondles. This is in obedience to the inevitable and immutable law of the indestructibility of matter and force. Matter is tangible; force is intangible. Matter is found in states; force is responsible for the state. Matter is also found in kingdoms; force is again ruling it. The one is made to grow from within by the complicated power of nutrition; the other to increase from without by the simpler but tardier function of accretion. The organic and inorganic comprise everything
Natural family planning: Double standards on teats and condoms
Authors: N Hampton, D Mansour
Journal: BMJ (1993)

often does not have the same motivation, and, particularly in developing countries, a woman may have an unequal say in such a decision.If she feels unhappy living with such uncertainty and decides, from purely unselfish motives, to try a more reliable method of birth control, it is she who has to bear all the guilt imposed on her by the Catholic church.Surely such a situation can have been created only by men, and men with no understand- ing of the problems faced by women.ANNEJEWELL