tbuckley/cabot-search huggingface dataset:
New Drugs: Acne and psoriasis
Authors: G M Murphy, M W Greaves
Journal: BMJ (1988)

Acne vulgaris occurs in at least 90% of adolescents, and psoriasis affects about 2% of the population. Established treatments are successful in inducing remission in most cases, but the management of severely affected patients presents many therapeutic problems. Advances in treatment in recent years have come not only from the development of new drugs but also from new regimens for older methods of treatment. Though these treatments have generally proved to be beneficial, some have introduced unexpected complications. We review here recent advances in the treatment of acne and psoriasis, with comments on associated adverse side effects.
Registration of MRI - PET Images, Procedure and Validation
Authors: H. H. Holcomb, H. L. Loats, C. Tamminga, A. Summerfelt, A. Slusarcick, J. Links, R. F. Dannals, H. Ravert, A. Wilson, V. Villemagne, H. N. Wagner
Journal: Clinical Nuclear Medicine (1988)

Positron emission tomography (PET) provides diverse physiological measurements; magnetic resonance imaging (MRI) provides high resolution anatomical detail of the brain. An accurate and inexpensive method of registering brain images from these two modalities should substantially improve the interpretation of PET images acquired from patients afflicted with local pathological processes such as tumor, epilepsy, stroke and trauma. The following steps outline our procedure for generating registered MRI-PET brain images. (1) A tight face mask is individually molded and mask placement-replacement fit is recorded photographically. (2) "M" configuration plastic tubing is taped onto the mask surface and a paramagnetically active substance injected into it. (3) From sagittal MR images the bicommisural axis is estimated. (4) An oblique transaxial orientation is then used to acquire 3 mm thickness, no gap, interleaved MR images extending the full dorsoventral axis of the brain. (5) Plane specific, tube reference point locations are noted on each image and distances are determined, which serve as geometric "signatures" of unique locations on the mask. (6) PET images are then aquired with tubes filled with a solution of low level positron emitting isotope (5 - 50 microCuries/ml). Interimage fit accuracy is assessed by computing the error in distances measured in corresponding planes acquired by these two modalities. Image overlay software facilitates the stereotaxic analysis of anatomically defined physiological images.
Aldosterone — Villain or Bystander?
Authors: Robert G Dluhy, Gordon H Williams
Journal: New England Journal of Medicine (2004)

The two primary regulators of aldosterone secretion are potassium and the renin–angiotensin system. The latter is involved in volume homeostasis, with high salt intake suppressing the renin–angiotensin system and aldosterone levels and low salt intake having the opposite effect. Secondary hyperaldosteronism, a physiologic response to dietary salt restriction, promotes renal sodium conservation. In this setting, hyperaldosteronism is a bystander that has no cardiovascular consequences. Hyperaldosteronism emerges as villain in persons whose dietary salt intake is normal if the production of aldosterone is inappropriate for the level of sodium intake, resulting in excessive renal sodium retention, potassium wasting, hypertension, and cardiovascular . . .
Livedo Reticularis during Amantadine Treatment
Authors: D. I. Vollum, J. D. Parkes, D. Doyle
Journal: BMJ (1971)

Livedo reticularis is a common side effect of treatment with amantadine for Parkinson9s disease. Investigation of 40 such patients suggests that the livedo is a physiological response provoked by depletion of catecholamine stores in peripheral nerve terminals.
Differential effects of 5-aminolaevulinic acid photodynamic therapy and psoralen + ultraviolet A therapy on p53 phosphorylation in normal human skin in vivo
Authors: L.E. Finlan, N.M. Kernohan, G. Thomson, P.E. Beattie, T.R. Hupp, S.H. Ibbotson
Journal: British Journal of Dermatology (2005)

Phosphorylation of the tumour suppressor p53 by the CK2/FACT pathway plays a central role in suppressing ultraviolet (UV)-induced skin cancer in animal models. Although p53 protein stabilization is induced after solar-simulated irradiation of human skin in vivo, p53 phosphorylation has not been defined.To investigate the effects of clinically effective treatments for skin diseases including psoralen + UVA (PUVA) and photodynamic therapy (PDT) on p53 phosphorylation to determine whether the tumour-suppressing p53 kinase pathways are activated upon use of these therapies.We used antibodies to the ATM/ATR and CK2/FACT phosphorylation sites on p53.We found that p53 activation was induced selectively by PUVA treatment, while 8-oxo-7,8-dihydroguanine DNA damage was induced selectively by 5-aminolaevulinic acid (ALA)-PDT treatment. Importantly, PUVA treatment resulted in p53 kinase activation, as defined by p53 modification at AT (serine-15) and CK2/FACT (serine-392) sites within the proliferative compartment.These data demonstrate that PUVA provokes accumulation and phosphorylation of p53 by AT and CK2/FACT within critical proliferative focal points (as determined by p63 colocalization studies) where DNA damage may lead to tumorigenesis. PDT is mechanistically distinct in that there is a lower level of induction of p53 expression with no evidence of AT- or CK2/FACT-mediated phosphorylation. This suggests that the type of DNA damage created by the reactive oxygen species generated by ALA-PDT does not induce the p53 pathway classically required for the repair of DNA photoadducts induced by UV.
Calcium ion as intracellular messenger and cellular toxin.
Authors: H Rasmussen, P Barrett, J Smallwood, W Bollag, C Isales
Journal: Environmental Health Perspectives (1990)

Ca2+ serves a nearly universal intracellular messenger function in cell activation, but excess Ca2+ is also a cellular toxin. The possibility of Ca2+ intoxication is minimized by an elaborate autoregulatory system in which changes in Ca2+ influx rate across the plasma membrane are rapidly compensated for by parallel changes in Ca2+ efflux rate. By this mean, cellular Ca2+ homestasis is maintained so that minimal changes in total cell calcium and cytosolic Ca2+ concentration occur during sustained Ca2(+)-mediated responses. Rather than a sustained increase in cytosolic Ca2+ concentration, it is the localized cycling of Ca2+ across the plasma membrane that is the critically important Ca2+ messenger during the sustained phase of cellular responses mediated via surface receptors linked to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 hydrolysis gives rise to inositol(1,4,5)trisphosphate (IP3) and diacylglycerol (DAG). The IP3 acts to release Ca2+ from an intracellular pool, thereby causing a transient rise in cytosolic Ca2+ concentration. This transient Ca2+ signal activates calmodulin-dependent protein kinases transiently, and hence, causes the transient phosphorylation of a subset of cellular proteins that mediate the initial phase of the response. The DAG brings about the association of protein kinase C (PKC) with the plasma membrane where a receptor-mediated increase in Ca2+ cycling across the membrane regulates PKC activity. The sustained phosphorylation of a second subset of proteins by PKC mediates the sustained phase of the response. Hence, Ca2+ serves as a messenger during both phases of the cellular response, but its cellular sites of action, its mechanisms of generation, and its molecular targets differ during the initial and sustained phases of the response.(ABSTRACT TRUNCATED AT 250 WORDS)
Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability
Authors: Francesca Antonacci, Megan Y Dennis, John Huddleston, Peter H Sudmant, Karyn Meltz Steinberg, Jill A Rosenfeld, Mattia Miroballo, Tina A Graves, Laura Vives, Maika Malig, Laura Denman, Archana Raja, Andrew Stuart, Joyce Tang, Brenton Munson, Lisa G Shaffer, Chris T Amemiya, Richard K Wilson, Evan E Eichler
Journal: Nature Genetics (2014)
Professional Ethics and Primary Care Medicine: Beyond Dilemmas and Decorum
Authors: John Mihalevich
Journal: JAMA (1986)

"Medical-ethical problem-solving is not a generalizable and repeatable exercise in logic; it is an examination of the moral motivations and sensibilities which constitute us as a 'doctor' or a 'patient.' " This statement contained in the introduction promises a close examination of the day-by-day ethical considerations involved in the physician-patient relationship. In the subsequent five chapters, the authors present, in a generally readable and cohesive fashion, the concept of the primary care physician's role in a "new" form of ethics involving a sense of collaboration and mutual interdependence between the physician and patient. Initially, the reader is introduced to a character or virtue-based ethic termed the<i>moral imagination</i>. The moral imagination is defined as the character, ideals, integrity, and virtues of physicians that provide them with the background for moral problem solving. Primary care medicine is viewed as a unique area of medicine best suited to incorporate this system of ethics
Ultraviolet-A radiation induces adhesion molecule expression on human dermal microvascular endothelial cells
Authors: M. HECKMANN, B. EBERLEIN-KONIG, A. WOLLENBERG, B. PRZYBILLA, G. PLEWIG
Journal: British Journal of Dermatology (1994)

Ultraviolet radiation is capable of inducing numerous skin reactions. Considerable amounts of UVA radiation penetrate the epidermis and reach the microvascular endothelium of the papillary dermis. In order to investigate putative direct effects of UV radiation on endothelial cells, we studied adhesion molecule expression by immunostaining procedures and FACS analysis, following irradiation of normal human skin and cultured human dermal endothelial cells. Enhanced immunostaining for ICAM‐1 and E‐selectin was detected in biopsies taken after in vivo UVA and UVB irradiation, compared with non‐irradiated control skin. On cultured human dermal endothelial cells, however, ICAM‐1 and E‐selectin were inducible by UVA but not UVB. The induction was dose‐dependent, peaking at 20 J/cm2 for both adhesion molecules, and time‐dependent, peaking after 6 and 24 h for E‐selectin and ICAM‐1, respectively. Expression of VCAM‐1 and PECAM/EndoCAM/CD31 was unaffected by any UV‐radiation modality. The functional integrity of irradiated cells was monitored by an exclusion assay of the fluorescent dye 7‐AAD, and by staining for the cytoskeletal proteins actin and vimentin. Our results demonstrate that dermal microvascular endothelial cells are a critical and direct target of UVA, and suggest they may play a pivotal role in UV‐induced inflammatory skin conditions.
Acquired variation outweighs inherited variation in whole genome analysis of methotrexate polyglutamate accumulation in leukemia
Authors: Deborah French, Wenjian Yang, Cheng Cheng, Susana C. Raimondi, Charles G. Mullighan, James R. Downing, William E. Evans, Ching-Hon Pui, Mary V. Relling
Journal: Blood (2008)
Can cyclosporin A induce permanent remission of atopic dermatitis?
Authors: N. SEPP, P.O. FRITSCH
Journal: British Journal of Dermatology (1993)

Three adult patients, who had suffered from severe therapy-resistant atopic dermatitis since childhood, were treated with long-term (29, 44 and 22 months) low-dose (maintenance dose: 0.5-0.7 mg/kg) cyclosporin A (CyA). All responded rapidly within 3-5 weeks and exhibited only minor exacerbations during the first phases of therapy. No relapse occurred in any of the patients after drug withdrawal. All patients remained symptom-free, except for occasional very mild and easily manageable localized lesions, for follow-up periods of 34, 13 and 22 months. Side-effects were minimal or tolerable (mild hypertrichosis in two patients, a slight decrease of creatinine clearance in one). In contrast with the clinical improvement, all atopy-related parameters such as blood eosinophilia, elevated IgE levels and specific IgE (RAST) reactivity remained essentially unchanged, as were skin dryness and stigmata of atopy. It is concluded that long-term low-dose CyA treatment may lead to permanent or long-term total or subtotal remission of atopic dermatitis.
Incorporation of adenovirus in calcium phosphate precipitates enhances gene transfer to airway epithelia in vitro and in vivo.
Authors: A Fasbender, J H Lee, R W Walters, T O Moninger, J Zabner, M J Welsh
Journal: Journal of Clinical Investigation (1998)

Adenovirus (Ad)-mediated gene transfer to airway epithelia is inefficient because the apical membrane lacks the receptor activity to bind adenovirus fiber protein. Calcium phosphate (CaPi) precipitates have been used to deliver plasmid DNA to cultured cell lines. However, such precipitates are not effective in many primary cultures or in vivo. Here we show that incorporating recombinant adenovirus into a CaPi coprecipitate markedly enhances transgene expression in cells that are resistant to adenovirus infection. Enhancement requires that the virus be contained in the precipitate and viral proteins are required to increase expression. Ad: CaPi coprecipitates increase gene transfer by increasing fiber-independent binding of virus to cells. With differentiated cystic fibrosis (CF) airway epithelia in vitro, a 20-min application of Ad:CaPi coprecipitates that encode CF transmembrane conductance regulator produced as much CF transmembrane conductance regulator Cl- current as a 24-h application of adenovirus alone. We found that Ad:CaPi coprecipitates also increased transgene expression in mouse lung in vivo; importantly, expression was particularly prominent in airway epithelia. These results suggest a new mechanism for gene transfer that may be applicable to a number of different gene transfer applications and could be of value in gene transfer to CF airway epithelia in vivo.
RESULTS IN TREATMENT OF PARESIS BY INUNCTIONS OF MERCURY AND DRAINAGE OF THE CEREBROSPINAL FLUID
Authors: ALAN D. FINLAYSON
Journal: American Journal of Psychiatry (1918)

Fourteen paretics, who had been showing symptoms from nine months to several years received daily inunctions of mercurial ointment 50 per cent. Every tenth day a lumbar puncture was made and from 20 C. C. to 40 c. c. of fluid withdrawn, the amount depending on the pressure and the rapidity of the flow. A Wassermann reaction was done, using the blood serum; a globulin test, cell count, Lange's colloidal gold test, Wassermann reaction and a chemical test to determine the presence of mercury were done, using the fluid. In seven, or 50 per cent of the cases the blood Wassermann became negative and remained so for varying periods of time; one case had a negative blood at the time of admission and it remained so throughout the period of observation. In 6, or 43 per cent of the cases, the spinal fluid became negative and remained so for varying periods of time. In no instance did the blood or spinal fluid become negative and remain so. All cases had negative globulin tests at one or more examinations, but, with the exception of one case, more positives than negatives were obtained. The cell count showed an irregular decrease in all instances. In 4, or 28 per cent of the cases, the colloidal gold became negative, that is, was neither paretic nor luetic in type, but all showed "paretic curves" at some later examination. After 15 months' treatment a trace of mercury was found in 500 c. c. of grouped spinal fluids. No mercury was found on previous examinations. One case showed a good remission mentally, but all the serological findings remained strongly positive. Another case did not improve quite as much, but approached a state termed a remission, and has shown some negative serological findings. The remaining 12 cases showed no greater mental or physical changes than would be found in a similar group of untreated cases. The lack of correlation between the serological findings and mental conditions leaves little ground on which to base definite conclusions as to the value of the treatment. I wish here to express my appreciation of the assistance rendered by Dr. Paul G. Weston in performing the pathological, serological, and chemical examinations included in this study, and also to my colleagues who assisted in obtaining the specimens.
Localized cutaneous lymphoma
Authors: Pauline M. Dowd, Margaret F. Spittle, Neil P. Smith
Journal: British Journal of Dermatology (1984)

Journal Article Localized cutaneous lymphoma Get access Pauline M. Dowd, Pauline M. Dowd St John's Hospital, Lisle Street, London Search for other works by this author on: Oxford Academic Google Scholar Margaret F. Spittle, Margaret F. Spittle St John's Hospital, Lisle Street, London Search for other works by this author on: Oxford Academic Google Scholar Neil P. Smith Neil P. Smith St John's Hospital, Lisle Street, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s26, 1 July 1984, Pages 21–22, https://doi.org/10.1111/j.1365-2133.1984.tb05240.x Published: 01 July 1984
Distinctive exudative discoid and lichenoid chronic dermatosis (Sulzberger and Garbe) re-examined–1978
Authors: MARION B. SULZBERGER
Journal: British Journal of Dermatology (1979)

Journal Article Distinctive exudative discoid and lichenoid chronic dermatosis (Sulzberger and Garbe) re‐examined–1978 Get access MARION B. SULZBERGER MARION B. SULZBERGER 2785 Jackson Street, San Francisco, California 94115, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 100, Issue 1, 1 January 1979, Pages 13–20, https://doi.org/10.1111/j.1365-2133.1979.tb03565.x Published: 01 January 1979
Workgroup Report: Incorporating <i>In Vitro</i> Alternative Methods for Developmental Neurotoxicity into International Hazard and Risk Assessment Strategies
Authors: Sandra Coecke, Alan M Goldberg, Sandra Allen, Leonora Buzanska, Gemma Calamandrei, Kevin Crofton, Lars Hareng, Thomas Hartung, Holger Knaut, Paul Honegger, Miriam Jacobs, Pamela Lein, Abby Li, William Mundy, David Owen, Steffen Schneider, Ellen Silbergeld, Torsten Reum, Tomas Trnovec, Florianne Monnet-Tschudi, Anna Bal-Price
Journal: Environmental Health Perspectives (2007)

This is the report of the first workshop on Incorporating In Vitro Alternative Methods for Developmental Neurotoxicity (DNT) Testing into International Hazard and Risk Assessment Strategies, held in Ispra, Italy, on 19-21 April 2005. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and jointly organized by ECVAM, the European Chemical Industry Council, and the Johns Hopkins University Center for Alternatives to Animal Testing. The primary aim of the workshop was to identify and catalog potential methods that could be used to assess how data from in vitro alternative methods could help to predict and identify DNT hazards. Working groups focused on two different aspects: a) details on the science available in the field of DNT, including discussions on the models available to capture the critical DNT mechanisms and processes, and b) policy and strategy aspects to assess the integration of alternative methods in a regulatory framework. This report summarizes these discussions and details the recommendations and priorities for future work.
A multi-centre phase 2 study of azacitidine in chronic myelomonocytic leukaemia
Authors: M W Drummond, C Pocock, M Boissinot, J Mills, J Brown, P Cauchy, N C P Cross, S Hartley, J Kell, A Szubert, P N Cockerill, D T Bowen
Journal: Leukemia (2014)
Is the death rate from asthma exaggerated? Evidence from west Cumbria.
Authors: W T Berrill
Journal: BMJ (1993)

Although the death rate from asthma in England and Wales is reported to be about 2000 a year, clinical experience suggests that it is much rarer. Doctors in West Cumbria health district could recall only seven cases in 14 years. Examination of case notes of patients officially recorded as dying of asthma showed that many were aged over 60 and cigarette smokers. An alternative cause of death was evident in over half the patients. If the picture is representative of that in the whole of Britain the reported mortality from asthma may be much too high.
THE ACTION OF GLYCOL ALDEHYD AND GLYCERIN ALDEHYD IN DIABETES MELLITUS AND THE NATURE OF ANTIKETOGENESIS
Authors: R. T. WOODYATT
Journal: JAMA (1910)

nized that a glycosuria persisting under a carbohydratefree diet may be made to disappear if the protein of the food is cut down.Falta, Gigon18 and others have shown that some patients may have a marked susceptibility to protein; more so, in fact, than to-carbohydrate ; so that glycosuria may he lessened or at least not increased by cutting down the protein and at the same time adding carbohydrate.The fact is certainly now well estab¬ lished that high protein feeding is not desirable in severe cases.Two bund red grams of cooked meat per
Topiramate for Migraine Prevention&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
Authors: Jan Lewis Brandes
Journal: JAMA (2004)

Small open-label and controlled trials suggest that the antiepileptic drug topiramate is effective for migraine prevention.To assess the efficacy and safety of topiramate for migraine prevention in a large controlled trial.A 26-week, randomized, double-blind, placebo-controlled study was conducted during outpatient treatment at 52 North American clinical centers. Patients were aged 12 to 65 years and had a 6-month history of migraine (International Headache Society criteria) and 3 to 12 migraines a month but no more than 15 headache days a month during a 28-day prospective baseline phase.After a washout period, patients meeting entry criteria were randomized to topiramate (50, 100, or 200 mg/d) or placebo. Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or maximum tolerated dose, whichever was less. Patients continued receiving that dose for 18 weeks.The primary efficacy measure was change from baseline in mean monthly migraine frequency. Secondary efficacy measures included responder rate (proportion of patients with > or =50% reduction in monthly migraine frequency), reductions in mean number of monthly migraine days, severity, duration, and days a month requiring rescue medication, and adverse events. The month of onset of preventive treatment action was assessed.Of 483 patients randomized, 468 provided at least 1 postbaseline efficacy assessment and comprised the intent-to-treat population. Mean monthly migraine frequency decreased significantly for patients receiving topiramate at 100 mg/d (-2.1, P =.008) and topiramate at 200 mg/d (-2.4, P<.001) vs placebo (-1.1). Statistically significant reductions (P<.05) occurred within the first month with topiramate at 100 and 200 mg/d. The responder rate was significantly greater with topiramate at 50 mg/d (39%, P =.01), 100 mg/d (49%, P<.001), and 200 mg/d (47%, P<.001) vs placebo (23%). Reductions in migraine days were significant for the 100-mg/d (P =.003) and 200-mg/d (P<.001) topiramate groups. Rescue medication use was reduced in the 100-mg/d (P =.01) and 200-mg/d (P =.005) topiramate groups. Adverse events resulting in discontinuation in the topiramate groups included paresthesia, fatigue, and nausea.Topiramate showed significant efficacy in migraine prevention within the first month of treatment, an effect maintained for the duration of the double-blind phase.