tbuckley/cabot-search huggingface dataset:
Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility
Authors: Lillian Cruz-Orengo, Brian P. Daniels, Denise Dorsey, Sarah Alison Basak, José G. Grajales-Reyes, Erin E. McCandless, Laura Piccio, Robert E. Schmidt, Anne H. Cross, Seth D. Crosby, Robyn S. Klein
Journal: Journal of Clinical Investigation (2014)

Multiple sclerosis (MS) is an inflammatory disease of the CNS that is characterized by BBB dysfunction and has a much higher incidence in females. Compared with other strains of mice, EAE in the SJL mouse strain models multiple features of MS, including an enhanced sensitivity of female mice to disease; however, the molecular mechanisms that underlie the sex- and strain-dependent differences in disease susceptibility have not been described. We identified sphingosine-1-phosphate receptor 2 (S1PR2) as a sex- and strain-specific, disease-modifying molecule that regulates BBB permeability by destabilizing adherens junctions. S1PR2 expression was increased in disease-susceptible regions of the CNS of both female SJL EAE mice and female patients with MS compared with their male counterparts. Pharmacological blockade or lack of S1PR2 signaling decreased EAE disease severity as the result of enhanced endothelial barrier function. Enhanced S1PR2 signaling in an in vitro BBB model altered adherens junction formation via activation of Rho/ROCK, CDC42, and caveolin endocytosis-dependent pathways, resulting in loss of apicobasal polarity and relocation of abluminal CXCL12 to vessel lumina. Furthermore, S1PR2-dependent BBB disruption and CXCL12 relocation were observed in vivo. These results identify a link between S1PR2 signaling and BBB polarity and implicate S1PR2 in sex-specific patterns of disease during CNS autoimmunity.
The Marsupialization Operation for Pilonidal Sinus
Authors: Knowles B. Lawrence, William J. Baker
Journal: New England Journal of Medicine (1951)

THE LARGE number of papers written on the surgical management of pilonidal sinus, each usually describing some new or different surgical technic, is eloquent testimony to the fact that results in many cases have been far from satisfactory. Inadequacies of follow-up studies often apparent in these reports, particularly those based on cases treated in the Armed Forces during World War II,1 2 3 have made evaluation of various operative procedures difficult. With Armed Forces personnel the follow-up lasted usually only until the patient returned to duty. Our experience has shown that a large percentage of recurrences develop at a later date, although . . .
Spinal leptin contributes to the pathogenesis of neuropathic pain in rodents
Authors: Grewo Lim, Shuxing Wang, Yi Zhang, Yinghong Tian, Jianren Mao
Journal: Journal of Clinical Investigation (2009)

Pain after nerve injury, a phenomenon referred to as neuropathic pain, is a debilitating clinical condition, but the underlying mechanisms remain unclear. As leptin, an adipocytokine produced mainly by nonneuronal tissue, has been implicated in the regulation of neuronal functions, we examined the role of leptin in neuropathic pain using a rat model of the condition chronic constriction sciatic nerve injury (CCI). We report that leptin critically contributed to pain behaviors following CCI. Specifically, spinal administration of a leptin antagonist prevented and reversed neuropathic pain behaviors in rats. Further examination revealed that levels of both leptin and the long form of the leptin receptor (Ob-Rb) were substantially increased within the ipsilateral spinal cord dorsal horn after peripheral nerve injury. Mechanistic studies showed that leptin upregulated the expression of both the spinal NMDA receptor and IL-1β through the JAK/STAT pathway. Furthermore, these CCI-induced behavioral and cellular responses were diminished in leptin-deficient mice and mimicked by spinal administration of exogenous leptin in naive rats. Our findings reveal a critical role for spinal leptin in the pathogenesis of neuropathic pain and suggest what we believe to be a novel form of nonneuronal and neuronal interactions in the mechanisms of pathological pain.
Correction: Letter on Dexamethasone Testing
Authors: PAUL J. GREEN
Journal: Annals of Internal Medicine (1984)

Letters and Corrections1 July 1984Correction: Letter on Dexamethasone TestingPAUL J. GREEN, PH.D.PAUL J. GREEN, PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-101-1-151_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In our letter in the May issue (1), an editorial change in sentence construction leads the reader to a change in meaning. Line 6 in the first paragraph should read, ". . . the nonspecificity of serum acid phosphatase values determined for the prostate . . .", rather than in the prostate....Reference1. FALLON J and GREEN P. A false-positive response in dexamethasone testing [Letter]. Ann Intern Med. 1984;100:770. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: PAUL J. GREEN, PH.D.Affiliations: Jefferson Medical College Philadelphia, PA 19107 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDHEA Cytokine Dysregulation in Aging and AIDS 1 July 1984Volume 101, Issue 1 Page: 151-151 Keywords Acid phosphatase ePublished: 1 December 2008 Issue Published: 1 July 1984 PDF downloadLoading ...
Chlorpheniramine-Dependent Thrombocytopenia
Authors: Eric V. Eisner
Journal: JAMA (1975)

SEVERE thrombocytopenia, as a consequence of an immune reaction, is a rare complication of therapy with a wide variety of drugs.1With respect to the antihistamines, antibody-mediated thrombocytopenia has been demonstrated in only a single case in which antazoline hydrochloride was implicated.2We report a case of chlorpheniramine-induced thrombocytopenic purpura in which serologic study established the presence of a drug-dependent IgG antiplatelet antibody. The patient's serum displayed antiplatelet activity in the presence of the closely related compound, brompheniramine maleate, but did not react with other antihistamines.  Report of a Case  A 53-year-old man was hospitalized on Sept 20, 1973, with generalized petechiae, hematuria, and melena. In the spring and summer of 1951 he had been hospitalized three times for severe acute thrombocytopenia. Each episode had followed an upper respiratory tract infection, and complete recovery had occurred spontaneously within two weeks. In August 1951 he underwent splenectomy, despite a
OVARIOTOMY IN THE AGED.Read before the Mississippi Valley Medical Association at Indianapolis.
Authors: RUFUS B. HALL
Journal: JAMA (1894)

To define clearly the limits of my topic, ovariotomy in the aged, I will take the Biblical division, that of three-score and ten years, and confine my remarks to patients who are 70 or more years of age. It is generally conceded as true, that any operation upon the old does not promise as good results as the same operation would upon the young, or patients in middle life. Especially is this true, in reference to all abdominal operations necessitating a hard strain upon the system from shock, or from traumatism to vital organs during the operation, as we not infrequently have in the removal of large ovarian tumors. Most writers, in reporting their operations upon the old women, and most textbooks, would have us believe that women 70 years old and upward are exceedingly bad subjects for ovariotomy. I am strongly inclined to the opinion that this is an
Prophylaxis against early anaphylactic reactions to snake antivenom
Authors: D. E Ball, K. Tisocki, H. W. Fan
Journal: BMJ (1999)

Editor—Fan et al’s paper is the second in the BMJ recently to investigate prophylaxis against adverse effects of snake antivenom.1 Earlier, Premawardhena et al in Sri Lanka concluded that giving low dose subcutaneous adrenaline before antivenom could prevent acute adverse reactions.2 The Brazilian study (by Fan et al) showed no benefit in using promethazine as pretreatment.1 Perhaps more interesting than the conclusions, however, is that both these clinical trials were stopped early because of interim analyses; they provide examples of the use and pitfalls of such analyses.

The Sri Lankan group stopped recruitment halfway through its study since the analysis showed a significant reduction in all acute adverse effects when adrenaline was used as pretreatment rather than placebo (P=0.0002). Unfortunately, in subanalysis of the severity of adverse reactions in the two groups the differences in incidence of mild, moderate, and severe reactions barely reached significance due to the low power of the analysis (about 50%) and the small numbers. This is important since it is mainly the moderate and severe reactions that we wish to prevent. As it was, the trial was stopped because of a supposed benefit, but we cannot advise the use of subcutaneous adrenaline because of unconvincing evidence. In the Brazilian study the interim analysis was in the form of sequential analysis. The use of this method, and to some degree the negative outcome of the study, prevents arguments of the nature used above.

Interim analyses are often required on ethical grounds, but final data analysis and clinical importance should be borne in mind when they are planned. Too often, emphasis is put on the ethics of continuing a trial in which some patients receive an apparently inferior treatment. Stopping the trial may, however, result in the evidence for the supposedly better treatment being insufficient for policy changes to be recommended—this too is unethical.

Using and stating defined methodologies, as in Fan et al’s study, can help, but we must always bear in mind that statistics are an aid to reason, not a replacement for it. The dangers of stopping a trial too early have been addressed recently by Pocock and White3 and need to be fully appreciated by clinical researchers.
Ionizing Radiation Causes a Dose-Dependent Release of Transforming Growth Factor α<b><i>In vitro</i></b>from Irradiated Xenografts and during Palliative Treatment of Hormone-Refractory Prostate Carcinoma
Authors: Michael Hagan, Adly Yacoub, Paul Dent
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Characterize the radiation response for transforming growth factor (TGF) α shedding in vitro and in vivo. We also report the shedding of TGF α by patients undergoing irradiation for hormone-refractory prostate cancer. Experimental Design: TGF α levels were determined by ELISA. DU145 xenografts were established on the flanks of athymic nu/nu mice. Expression of phospho-extracellular signal-regulated kinase (ERK)1/2 and phospho-epidermal growth factor receptor (EGFR) and the DNA repair proteins XRCC1 and ERCC1 were determined by Western analyses. Results: Exposure to ionizing radiation results in a dose-dependent release of TGF α. Once released, TGF α stimulates EGFR-ERK1/2 signaling in unirradiated cells. Blockade of the EGFR with the tyrphostin AG1478 eliminates the up-regulation XRCC1 and ERCC1 by TGF α or irradiation. After irradiation, cells are refractory to additional transactivation of EGFR by additional irradiation for 8 to 12 hours. Irradiation during this refractory period does not increase the expression of XRCC1 or ERCC1. Ligand activation of EGFR is maintained during the refractory period. Irradiation of DU145 xenografts also results in the activation of ERK1/2, release of TGF α, and a similar refractory period. Ionizing irradiation also results in the release of TGF α for patients undergoing radiation therapy for hormone-refractory prostate cancer. Conclusions: Irradiation results in a dose-dependent increase in TGF α capable of enhancing the growth of DU145 xenografts. TGF α is also shed following radiation therapy of patients treated for hormone-refractory prostate cancer. Radiation transactivation of the EGFR produces a radio-refractory period, which lasts for several hours. During this period, additional irradiation fails to induce XRCC1, ERCC1, or additional TGF α release.
Genome-wide association study identifies sequence variants on 6q21 associated with age at menarche
Authors: Patrick Sulem, Daniel F Gudbjartsson, Thorunn Rafnar, Hilma Holm, Elinborg J Olafsdottir, Gudridur H Olafsdottir, Thorvaldur Jonsson, Peter Alexandersen, Bjarke Feenstra, Heather A Boyd, Katja K Aben, Andre L M Verbeek, Nel Roeleveld, Aslaug Jonasdottir, Unnur Styrkarsdottir, Valgerdur Steinthorsdottir, Ari Karason, Simon N Stacey, Julius Gudmundsson, Margret Jakobsdottir, Gudmar Thorleifsson, Gudmundur Hardarson, Jeffrey Gulcher, Augustine Kong, Lambertus A Kiemeney, Mads Melbye, Claus Christiansen, Laufey Tryggvadottir, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2009)
Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: A double-blind randomized controlled trial
Authors: Saifudin Khalid, Robert Murdoch, Amy Newlands, Kevin Smart, Angela Kelsall, Kimberley Holt, Rachel Dockry, Ashley Woodcock, Jaclyn A. Smith
Journal: Journal of Allergy and Clinical Immunology (2014)
DISLOCATIONS, UPWARDS AND BACKWARDS, OF THE SCAPULAR END OF THE CLAVICLE.Read in the Section of Surgery and Anatomy, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May 5, 1891.
Authors: WM. H. DOUGHTY
Journal: JAMA (1891)

In the July No. of the<i>Richmond and Louisville Medical Journal</i>(now<i>Gaillard's Medical Journal</i>), for 1876, I published an article entitled: "True Method of Treating Dislocations, upwards and backwards, of the Scapular end of the Clavicle, with report of a case illustrating the principle employed." According to standard authorities such injuries are rare and their treatment extremely unsatisfactory. Since 1876 I have seen but two cases, both of which occurred within a few months of each other in 1888: one in my own practice, report of which accompanies this paper; the other in that of my friend and neighbor, Prof. Thos. R. 'Wright, of this city, through whose courtesy I am permitted to refer to it, and report an excellent result from the method of treatment given herein. My first case was published in illustration of a new principle in the management of such injuries, and
Patients' preferences need thinking through for the NHS
Authors: A. P Bowling
Journal: BMJ (2003)

EDITOR-Kennedy comments that a mature culture will settle on sharing power and responsibility, on a subtle negotiation between professional and patient about what each wants and what each can deliver.1But how will clinicians and health policy makers react to patients who want the least effective treatment, which may also be less cost effective for the health service in the longer term?That this scenario could arise is indicated by the results of our pilot survey among patients with angina of their preferred treatment for coronary artery disease.Patients' views on the range of invasive to less invasive treatments were diverse.However, although surgical treatments (such as coronary bypass surgery) were generally perceived as effective, they were also described by respondents in negative terms, such as invasive and frightening, and were to be avoided altogether or delayed until they became unavoidable (until the condition becomes life threatening).This attitude was particularly prevalent in women and in older patients (aged 75 and over).A larger study, including modelling the results on healthcare costs and outcomes, is required next, but the consequences for the NHS of large numbers of patients opting for treatments other than those that are clinically indicated need thinking through.
Re: Active Tamoxifen Metabolite Plasma Concentrations After Coadministration of Tamoxifen and the Selective Serotonin Reuptake Inhibitor Paroxetine
Authors: B. Ratliff, E. C. Dietze, G. R. Bean, C. Moore, S. Wanko, V. L. Seewaldt
Journal: JNCI Journal of the National Cancer Institute (2004)
Effect of Cigarette-smoking on Blood Flow Through the Hand
Authors: J. T. Shepherd
Journal: BMJ (1951)

The death rates from suffocation "in bed " show a tendency to decline recently.Again this might be due to more bottle-feeding, with the result that fewer mothers go to sleep and thereby suffocate their babies while breast-feeding them in bed.But there seems to have been during the decade a slight rise in the death rates from suffocation "in cot, cradle, etc.," and the two may be related.Higher wages have enabled more parents than formerly to buy cots if they wish to do so, and the babies may be placed in them in preference to beds containing other occupants. ConclusionThe importance of precisely ascertaining the cause before attributing the death of a baby to accidental mechanical suffocation lies in the effect that such a diagnosis may have on the parents.Few would not bitterly reproach themselves for having 'contributed, however unwittingly, to the death of their baby.Yet many whose baby's death is so recorded, even though ignorant of the dangers of taking a baby into their bed, or laying it face down on a soft pillow, are in fact innocent of allowing their baby to die of suffocation.Especially is this true when babies are found dead in cots and cradles, as the sex ratios show. SummaryThe sex ratios of infant deaths from accidental mechanical suffocation in various clrcumstances suggest that the causes of death in cots and cradles differ considerably from the causes of death in bed and by food.Published evidence is cited indicating that in any case only a minority of these deaths are due to suffocation.Recently, death rates for suffocation "in bed" have declined, while those for suffocation "in cot, cradle, etc.," and "by food" have risen.No infant's death should be attributed to accidental mechanical suffocation unless there is clear positive evi- dence of it.
Sterilisation of young, competent, and childless adults
Authors: Piers Benn, Martin Lupton
Journal: BMJ (2005)

Is it ethical to sterilise a young woman who is determined she never wants children, even if there are no strong medical reasons to avoid pregnancy? 

A 26 year old woman presented to a general gynaecology clinic requestingsterilisation. She worked as the manager of a large legal practice in central London. She had never been pregnant. She was in a relationship that had lasted five years and was using condoms for contraception. At the age of 17she had discovered that she had a serious congenital heart defect. Neither she nor her partner had any desire to have children, and they had spoken about this at some length.

The reasons she gave for requesting sterilisation were that she did not have faith in other forms of contraception; had no desire to have children;did not wish to change her lifestyle or threaten her financial status (she saw children as a financial burden); felt that children would prohibit manyimportant life choices, including the opportunity to travel; thought the world was already burdened with enough people; and had serious anxieties about the risk of medical complications during a pregnancy as her cardiologist had told her that pregnancy would be risky.

The gynaecologist suggested alternative and reversible methods of contraception, including the intrauterine progestogen system. He also asked whether her partner would consider vasectomy. He explained the risks of laparoscopic sterilisation, which include a small risk of death and a risk of about1 in 300 of requiring an emergency laparotomy to repair damage done to internal organs. The patient declined the intrauterine system and refused to ask her partner to have a vasectomy as he was only 25. She explained that, should she die prematurely, he might meet a new partner who wanted to have children.

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Rapid Blood Ketone Body Estimation in the Diagnosis of Diabetic Ketoacidosis
Authors: K. G. M. M. Alberti, T. D. R. Hockaday
Journal: BMJ (1972)

Different methods of assessing ketone body concentrations in blood and plasma of ketoacidotic patients have been compared. We confirmed that Ketostix reacts strongly with acetoacetate, giving a useful range of 0 to 10 mM for plasma acetoacetate, that acetone reacts weakly, and that 3-hydroxybutyrate does not react at all. Plasma Ketostix readings correlated only moderately well with enzymatically determined whole-blood acetoacetate. All samples giving a + + + reaction contained more than 1.6 mM acetoacetate while only 4 out of 21 samples showing 0 contained more than 0.4 mM. Comparison of Ketostix readings with total blood ketone body content showed poor correlation. One reason for this was the large variation in the ratio of 3-hydroxybutyrate to acetoacetate in ketoacidosis; another was that often Ketostix had been stored in such a way that they had become damp, which impairs their reliability. If the Ketostix reading and estimation of the blood pH show a discrepancy we suggest that an enzymatic assay should be used to determine the ketone bodies and lactate.
Paradoxical Responses of Plasma Cortisol, Adrenocorticotropic Hormone and Growth Hormone to Thyrotropin-Releasing Hormone and Luteinizing-Hormone-Releasing Hormone in Anorexia nervosa Patients
Authors: Hajime Tamai, Nobuyuki Kobayashi, Shuji Fukata, Yoshihiko Hirota, Sunao Matsubayashi, Tetsuya Nakagawa, Michael C. Okimura, Robert M. Walter, Jr., Lindy F. Kumagai
Journal: Psychotherapy and Psychosomatics (1986)

Abnormalities of hypothalamic-pituitary function in patients with anorexia nervosa (AN) have been reported previously. Since atypical responses to thyrotropin-releasing hormone (TRH) and luteinizing-hormone-releasing hormone (LHRH) have been observed in other disease states, hormonal responses to these hypothalamic peptides in 60 otherwise unstressed young women with anorexia nervosa were studied. Sixteen patients demonstrated a growth hormone (GH) response to TRH and 10 showed an increase in GH after LHRH. Five patients had an increase in cortisol after TRH, 2 of whom showed GH response, and 2 patients demonstrated a cortisol response to LHRH, 1 of whom had a GH response. Variable TSH responses to TRH were observed in the study but there was no correlation with the occurrence of GH or cortisol responses. GH responses to TRH and LHRH were typically not seen in the same patients, nor were they predictive of a cortisol response to the same stimulus. These data add to the evidence for an abnormal hypothalamic-pituitary regulation in AN.
High resolution localization of endothelin receptors in rat renal medulla
Authors: Tokihito Yukimura, Mitsuru Notoya, Kenji Mizojiri, Vinci Mizuhira, Takeshi Matsuura, Tsuneyuki Ebara, Katsuyuki Miura, Shokei Kim, Hiroshi Iwao, Keifu Song
Journal: Kidney International (1996)