tbuckley/cabot-search huggingface dataset:
Deficiency in Serum Immunoglobulin (Ig)m Predisposes to Development of Igg Autoantibodies
Authors: Michael R. Ehrenstein, H. Terence Cook, Michael S. Neuberger
Journal: The Journal of Experimental Medicine (2000)

Serum immunoglobulin (Ig)M provides the initial response to foreign antigen and plays a regulatory role in subsequent immune response development, accelerating the production of high-affinity IgG. Here we show that mice deficient in serum IgM have an increased propensity to spontaneous autoimmunity as judged by the development with age of serum IgG anti-DNA antibodies and the renal deposition of IgG and complement. They also exhibit augmented anti-DNA IgG production on exposure to lipopolysaccharide. Thus, deficiency in serum IgM leads to diminished responsiveness to foreign antigens but increased responsiveness to self—a paradoxical association reminiscent of that described in humans deficient in complement or IgA. We wondered whether serum IgM might play an analogous role with regard to the response to self-antigens. However, here—in contrast to the sluggish response to foreign antigens—we find that deficiency in serum IgM actually predisposes to the development of IgG antibodies to autoantigens.
Compliance and reactivity of the peripheral venous system in chronic intermittent hemodialysis
Authors: Jeroen P. Kooman, Jef A.G. Wijnen, Petra Draaijer, Luc M.A.B. van Bortel, Ulrich Gladziwa, Henricus G. Peltenburg, Harry A.J. Struyker-Boudier, Johannes P. van Hooff, Karel M.L. Leunissen
Journal: Kidney International (1992)
US hospitals face shortages of anaesthesia drug as supplies are diverted for executions
Authors: I. Torjesen
Journal: BMJ (2012)

US hospitals are facing shortages of a key surgical anaesthetic drug because death rows use the same drug in executions and are stockpiling supplies, according to figures obtained under freedom of information legislation by the legal action charity Reprieve.

The US Food and Drug Administration (FDA) has repeatedly warned that the country is facing shortages of pancuronium bromide, a paralysing agent designed …
Sphincter of Oddi Manometry: Comparison of Microtransducer and Perfusion Methods
Authors: M. Tanaka, S. Ikeda
Journal: Endoscopy (1988)

There are two approaches to endoscopic sphincter of Oddi manometry, the microtransducer method and the perfusion method. Data reported by us and others are reviewed, with the aim of comparing the two techniques. Biliary pressure, pancreatic duct pressure, and sphincter of Oddi phasic wave activity can be measured by both of these methods. Easy handling and the capability of recording the mode of phasic wave propagation with a multilumen catheter are present advantages of perfusion manometry over the microtransducer method. Because there is no need for perfusion of fluid, the equipment needed for microtransducer manometry is simpler than that needed for the perfusion method, and the microtransducer technique may be more suitable for prolonged recording. An inter-study comparison of manometric data is easier with microtransducer manometry, but must await the collection of more data. Manometric differences between various diseases are still inconsistent, whereas there is no question of the effect of sphincterotomy on pressure values, with the exception of pancreatic duct and sphincter pressures. The possibilities of diagnosing sphincter of Oddi dysfunction, and of predicting the response to sphincterotomy have been received with enthusiasm. However, whether the findings obtained by endoscopic manometry over relatively short periods of time can be considered representative of overall sphincter function is now being questioned since the presence of physiologic cyclic changes in sphincter of Oddi phasic activity in phase with the migrating motor complex of the duodenum was demonstrated. Hormonal or pharmacological stimulation of sphincter activity may help us overcome this problem.
Is the metabolism of testosterone to 5α-dihydrotestosterone required for androgen action in the skin?
Authors: VALERIE A. RANDALL, F. J. EBLING
Journal: British Journal of Dermatology (1982)

Journal Article Is the metabolism of testosterone to 5α‐dihydrotestosterone required for androgen action in the skin? Get access VALERIE A. RANDALL, VALERIE A. RANDALL Department of Zoology, The University of Sheffield, Sheffield S10 2TN Search for other works by this author on: Oxford Academic Google Scholar F. J. EBLING F. J. EBLING Department of Zoology, The University of Sheffield, Sheffield S10 2TN Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 107, Issue s23, 1 November 1982, Pages 47–53, https://doi.org/10.1111/j.1365-2133.1982.tb01031.x Published: 01 November 1982
John Henry McKnight Pinkerton
Authors: I. MacGillivray
Journal: BMJ (2013)

After house posts in Belfast John Henry McKnight Pinkerton (“Jack”) served from 1945 to 1947 in the Royal Navy with a flotilla of minesweepers in the Mediterranean, based in Malta. When he returned to Belfast in 1947 he married Florence McKinstry, also a doctor. He was appointed a lecturer in Belfast and then senior lecturer in obstetrics and gynaecology at the University of the West Indies, where he …
UK government likely to miss its target to reduce childhood obesity
Authors: Andrew Cole
Journal: BMJ (2006)

A novel membrane-permeant derivative of cAMP, cAMP acetoxymethyl ester (cAMP/AM), was synthesized via silylated intermediates. Its ability to induce Cl- secretion by T84 cells, a human colon cancer cell line, was compared with that of two other membrane-permeant cAMP derivatives that were recently introduced, N6,O29-dibutyryl-cAMP acetoxymethyl ester (bt2cAMP/AM) and Sp-5,6-dichlorobenzimidazole-1-beta-D-ribofuranoside 39,59-cyclic phosphorothioate (Sp-5,6-DCl-cBIMPS). All of these compounds are powerful activators of Cl- secretion when applied extracellularly, with EC50 values of 60 microM, 0.7 microM, and 3 microM, respectively. However, cAMP/AM was expected to be readily degraded inside cells, in contrast to the cyclophosphodiesterase-resistant Sp-5,6-DCI-cBIMPS or the only slowly metabolizable N6-butyryl-cAMP derived from bt2cAMP/AM. Reversibility of cAMP/AM action was demonstrated by wash-out experiments; Cl- secretion induced by high doses of cAMP/AM (100 microM) could be quickly abolished by rinsing of the cells, whereas similar experiments with bt2cAMP/AM and Sp-5,6-DCI-cBIMPS showed much slower decreases. Even more sensitive to residual cAMP derivatives was the synergistic effect of carbachol, which was applied after the incubation with membrane-permeant derivatives and their subsequent wash-out. Although doses of cAMP derivatives that barely activated Cl- secretion were readily capable of inducing a synergistic response with carbachol, cells incubated with high doses of cAMP/AM (100 microM) and subsequently washed showed only a nonsynergistic carbachol response, in contrast to cells incubated with bt2cAMP/AM or Sp-5,6-DCI-cBIMPS. We therefore characterize cAMP/AM as a membrane-permeant derivative of cAMP that is easily metabolizable inside cells and hence is most useful for applications where a transient intracellular cAMP signal is desired. In contrast, completely nonmetabolizable Sp-5,6-DCI-cBIMPS seems to be more useful in longer incubations that require steady levels of cAMP-dependent protein kinase activation. bt2cAMP/AM combines the advantages of intracellular trapping by ester hydrolysis and reduced cyclophosphodiesterase sensitivity of its active intracellular product, which probably lead to its particularly high potency.
Hydroxyurea-Associated Leg Ulceration
Authors: Patricia J. Best
Journal: Annals of Internal Medicine (1998)

Letters1 August 1998Hydroxyurea-Associated Leg UlcerationPatricia J. Best, MD, Robert M. Petitt, MD, and Mark R. Pittelkow, MDPatricia J. Best, MDMayo Clinic; Rochester, MN 55905Search for more papers by this author, Robert M. Petitt, MDMayo Clinic; Rochester, MN 55905Search for more papers by this author, and Mark R. Pittelkow, MDMayo Clinic; Rochester, MN 55905Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-3-199808010-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:The observations of Dr. Kennedy and Disla and colleagues are interesting but deserve further comment. Kennedy and colleagues had performed many of the seminal clinical studies examining the activity and use of hydroxyurea. Their 1975 report did not specifically identify the distinctive painful leg ulcers that develop in patients receiving long-term hydroxyurea therapy [1]. We recently reported our findings on the lichenoid, dermatomyositis-like skin changes resulting from hydroxyurea therapy, changes similar to Kennedy and colleagues' initial observations [1, 2]. Most of the patients with leg ulcers that resulted from hydroxyurea did not have the atrophic, lichenoid changes reported ...References1. Kennedy BJ, Smith R, Goltz RW. Skin changes secondary to hydroxyurea therapy. Arch Dermatol. 1975; 111:183-7. Google Scholar2. Daoud MS, Gibson LE, Pittelkow MR. Hydroxyurea dermopathy: a unique lichenoid eruption complicating long-term therapy with hydroxyurea. J Am Acad Dermatol. 1997; 36:178-82. Google Scholar3. Lerner HJ, Beckloff GL, Godwin MC. Hydroxyurea (NSC-32065) intermittent therapy in malignant diseases. Cancer Chemotherapy, Reports. 1969; 53:385-95. Google Scholar4. Itin P, Winkelmann RK. Cutaneous manifestations in patients with essential thrombocythemia. J Am Acad Dermatol. 1991; 24:59-63. Google Scholar Author, Article, and Disclosure InformationAffiliations: Mayo Clinic; Rochester, MN 55905 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1998Volume 129, Issue 3Page: 252-253KeywordsHemoglobinMyeloproliferative disordersThrombocytosisUlcers Issue Published: 1 August 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Book: Encyclopedia of Death and Dying
Authors: J. Neuberger
Journal: BMJ (2001)

Eds Glennys Howarth, Oliver Leaman Routledge, £85, pp 560 ISBN 0 415 18825 3 Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> Although there have been textbooks and encyclopaedias on palliative care for decades now, the wider interdisciplinary study of death and dying is a relatively recent phenomenon. Academic study of death and dying within the social sciences—such as the masters' programme on death and society at Reading University—is new. Thanatology, the study of death, is almost unrecognised as a term, and the study of customs and taboos around death and dying has, for the best part of a century, been considered the province of the more obscurantist among anthropologists. So this volume deserves a profound welcome. Howarth and Leaman have attempted to deal … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Thyroid hormone regulates Na+-Ca2+ exchanger expression during postnatal maturation and in adult rabbit ventricular myocardium
Authors: S. R. Boerth, M. Artman
Journal: Cardiovascular Research (1996)

Expression of the cardiac Na(+)-Ca2+ exchanger (NCX) is high at birth and declines rapidly to adult levels by approximately 21 days in rabbits. The aim was to evaluate the role of thyroid hormone in regulating cardiac NCX expression.Adult New Zealand White rabbits were made hypothyroid by treatment with propylthiouracil or hyperthryoid by administration of sigma-thyroxine. Hypothyroidism was induced in immature rabbits by exposure to propylthiouracil from gestational day 25 through the first 21 days after birth. NCX steady-state mRNA levels were quantitated using Northern slot blots with poly(A+) RNA isolated from ventricular myocardium of treated and age-matched euthyroid animals. As a control, steady-state levels of cardiac sarco(endo)plasmic reticulum calcium ATPase (SERCA2a) were measured in each group. Thyroid status was confirmed with serum T4, ventricular weight and body weight measurements. Immunoreactive NCX protein levels were assessed using Western blots.Compared with euthyroid controls, NCX steady-state mRNA levels increased to 189 +/- 20% in hypothyroid adults and decreased to 55 +/- 15% in hyperthyroid adults. Opposite effects were observed for SERCA2a expression (58 +/- 7% in hypothyroidism and 130 +/- 15% in hyperthyroidism). In hypothyroid 21-day-old rabbits, NCX steady-state mRNA levels were elevated to 205 +/- 30% of age-matched euthyroid controls. SERCA2a levels were unaffected in the immature animals, possibly due to inability to reduce thyroid levels sufficiently to affect SERCA2a expression in this model. Changes in NCX mRNA levels produced comparable changes in immunoreactive NCX protein levels.Thyroid hormone reciprocally regulates NCX and SERCA2a expression in the ventricles of adult rabbits. Hypothyroidism resulted in sustained high levels of NCX expression in 21-day-old rabbits. These results suggest that the postnatal thyroid hormone surge is important for the normal down-regulation of cardiac NCX expression during the first 3 weeks after birth in developing rabbits.
Depression of Drug-metabolizing Activity in the Human Liver by Interferon-β
Authors: Hiroyasu Okuno, Masashi Takasu, Haruhiko Kano, Toshihito Seki, Yasuko Shiozaki, Kyoichi Inoue
Journal: Hepatology (1993)

The depressant effect of interferon beta on drug-metabolizing activity in the human liver was investigated. Seven patients with chronic hepatitis C were treated with interferon beta at doses of 3 x 10(6) to 9 x 10(6) IU/day for 8 wk. The activities of 7-methoxycoumarin O-demethylase and 7-ethoxycoumarin O-deethylase in specimens obtained by liver biopsy were examined before and after interferon treatment. Theophylline pharmacokinetics were also examined before and after interferon treatment. Interferon beta treatment reduced the activities of both O-dealkylases from 6.0 (100%) to 3.2 (53%) nmol/gm liver per minute and from 1.9 (100%) to 1.1 (58%) nmol/gm liver per minute, respectively (p < 0.05). The total body clearance of theophylline was also decreased (from 0.76 to 0.56 ml/kg/min; p < 0.05), and its elimination half-life was increased (from 8.4 to 11.7 hr; p < 0.05); however, the volume of distribution was not significantly affected. The magnitude of the decreases in enzyme activities and in theophylline clearance varied widely in individual patients and did not correlate with the dose of interferon administered. This study provides the first direct evidence that interferon beta can depress the activity of drug-metabolizing enzymes in the human liver.
Completely Implanted Defibrillator
Authors: John C. Schuder
Journal: JAMA (1970)

<h3>To the Editor.—</h3> In reference to your recent editorial comment entitled "Automatic Detection and Defibrillation of Lethal Arrhythmias—A New Concept"<sup>1</sup>, readers might be interested in a recent paper by our group<sup>2</sup>which, in a sense, supplements the paper by Mirowski and colleagues.<sup>3</sup> In contrast to the work reported by Mirowski et al, our approach involved electrodes implanted between the pectoralis major muscle and the rib cage, detection of fibrillation from the electrocardiographic signal, a quasi-trapezoidal defibrillatory shock, and a system small enough to be completely implanted. Some 73 successful defibrillatory episodes were reported in three dogs with completely implanted systems.
Narcosis and nightshade
Authors: A. J. Carter
Journal: BMJ (1996)

Although this year marks the 150th anniversary of the dfiscovery of modern surgical anaesthesia, surgery itself has a much longer history.It is well known that extracts from the opium poppy, Papaver somniferum, were used to dull the pain of surgery during ancient times but less well known that extracts from plants with sedative powers often accompanied them, producing primitive anaesthesia.Most of these sedative plants were members of a large botanical family, the Solanaceae.This paper describes some of them and discusses the ways in which they were administered.It also explains why, during the middle ages, these primitive techniques went out of use but how none the less they provided Shakespeare with the inspiration for some of his greatest plays.When the active principal of the Solanaceae was identified as scopolamine, it came to play a part in 20th century anaesthesia.The combination of omnopon and scopolamine lives on as a premedication, and the presence of poppy heads and mandrake roots on the arms oftoday's Association of Anaesthetists serves to remind us of the speciality's links with its past.Seven months after the performance of the first operation under ether anaesthesia the Lancet published a short extract from a paper in a provincial French
Critical issues in benzene toxicity and metabolism: the effect of interactions with other organic chemicals on risk assessment.
Authors: M A Medinsky, P M Schlosser, J A Bond
Journal: Environmental Health Perspectives (1994)

Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene are well documented and include aplastic anemia and pancytopenia. Some individuals exposed repeatedly to cytotoxic concentrations of benzene develop acute myeloblastic anemia. It has been hypothesized that metabolism of benzene is required for its toxicity, although administration of no single benzene metabolite duplicates the toxicity of benzene. Several investigators have demonstrated that a combination of metabolites (hydroquinone and phenol, for example) is necessary to duplicate the hematotoxic effect of benzene. Enzymes implicated in the metabolic activation of benzene and its metabolites include the cytochrome P450 monooxygenases and myeloperoxidase. Since benzene and its hydroxylated metabolites (phenol, hydroquinone, and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. Other organic molecules that are substrates for cytochrome P450 can inhibit the metabolism of benzene. For example, toluene has been shown to inhibit the oxidation of benzene in a noncompetitive manner. Enzyme inducers, such as ethanol, can alter the target tissue dosimetry of benzene metabolites by inducing enzymes responsible for oxidation reactions involved in benzene metabolism. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes, such as enzymatic oxidation, and deactivation processes, like conjugation and excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of extracellular potassium on ventricular automaticity and evidence for a pacemaker current in mammalian ventricular myocardium.
Authors: B G Katzung, J A Morgenstern
Journal: Circulation Research (1977)

Automaticity was induced in isolated guinea pig and cat papillary muscles by application of depolarizing constant current pulses. Increasing extracellular potassium from 1 to 15 mM caused a shift of pacemaker-like activity to less negative diastolic potentials and a decrease in maximum phase 4 slope. Membrane resistance, estimated from the relation of applied current to maximum diastolic potential, decreased when extracellular potassium was increased. Voltage clamps of cat papillary muscle demonstrated that action potentials activate a time-dependent outward current which has a reversal potential of -79.1 mV (+/- 0.99 SE, n = 20) at an extracellular potassium concentration of 5 mM. The reversal potential of this current varies with extracellular K+ with a slope of 50-60 mV per 10-fold concentration change. The current is activated by voltage clamps or action potential plateaus in the range of -30 to +30 mV. It has a time constant of deactivation which increases from approximately 100 to over 400 msec as clamp potential is increased from -90 to -60 mV. It is proposed that this current is equivalent to Ix1 demonstrated in other cardiac tissues and is responsible, in combination with inward currents, for automaticity in ventricular fibers.
What works in schizophrenia: Depot preparations may improve outcomes
Authors: Peter M Haddad, Omair Niaz
Journal: BMJ (2006)

EDITOR—The study by Tiihonen et al indicates that antipsychotics are not equally effective in treating schizophrenia.1 After a first admission with schizophrenia, patients treated with clozapine, olanzapine, or perphenazine depot had substantially lower risks of readmission, and discontinuation of treatment for any reason, than patients treated with oral haloperidol.



Credit: BSIP, PIKO/SPL



The increased effectiveness of clozapine is understandable in terms of its superior …
Soluble CD40 Ligand in Acute Coronary Syndromes
Authors: Christopher Heeschen, Stefanie Dimmeler, Christian W. Hamm, Marcel J. van den Brand, Eric Boersma, Andreas M. Zeiher, Maarten L. Simoons
Journal: New England Journal of Medicine (2003)

CD40 ligand is expressed on platelets and released from them on activation. We investigated the predictive value of soluble CD40 ligand as a marker for clinical outcome and the therapeutic effect of glycoprotein IIb/IIIa receptor inhibition in patients with acute coronary syndromes.Serum levels of soluble CD40 ligand were measured in 1088 patients with acute coronary syndromes who had previously been enrolled in a randomized trial comparing abciximab with placebo before coronary angioplasty and in 626 patients with acute chest pain.The levels of soluble CD40 ligand were elevated (above 5.0 microg per liter) in 221 patients with acute coronary syndromes (40.6 percent). Among patients receiving placebo, elevated soluble CD40 ligand levels indicated a significantly increased risk of death or nonfatal myocardial infarction during six months of follow-up (adjusted hazard ratio as compared with patients with low levels of the ligand [< or =5.0 microg per liter], 2.71; 95 percent confidence interval, 1.51 to 5.35; P=0.001). The prognostic value of this marker was validated in the patients with chest pain, among whom elevated soluble CD40 ligand levels identified those with acute coronary syndromes who were at high risk for death or nonfatal myocardial infarction (adjusted hazard ratio as compared with those with low levels of the ligand, 6.65; 95 percent confidence interval, 3.18 to 13.89; P<0.001). The increased risk in patients with elevated soluble CD40 ligand levels was significantly reduced by treatment with abciximab (adjusted hazard ratio as compared with those receiving placebo, 0.37; 95 percent confidence interval, 0.20 to 0.68; P=0.001), whereas there was no significant treatment effect of abciximab in patients with low levels of soluble CD40 ligand.In patients with unstable coronary artery disease, elevation of soluble CD40 ligand levels indicated an increased risk of cardiovascular events. Elevation of soluble CD40 ligand identifies a subgroup of patients at high risk who are likely to benefit from antiplatelet treatment with abciximab.
Spanish hospital offers genetic test for familial Alzheimers
Authors: P. Rigg
Journal: BMJ (2002)

A clinic in Spain is offering a genetic testing and follow up service for patients who think that they are at risk of developing early onset, familial Alzheimer's disease.

The Clinic of Barcelona Hospital offers the service to people from families considered at risk, in which three people, over two generations, have developed the disease. They test for mutations on chromosome 14, 1, and 21. If the test is positive, the patient is likely to develop the disease before the age of 60.

The fact that doctors …