tbuckley/cabot-search huggingface dataset:
Lincoln Logged Incorrectly—Reply
Authors: Stephen J. Greenberg
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Clinical implementation of integrated whole-genome copy number and mutation profiling for glioblastoma
Authors: Shakti H. Ramkissoon, Wenya Linda Bi, Steven E. Schumacher, Lori A. Ramkissoon, Sam Haidar, David Knoff, Adrian Dubuc, Loreal Brown, Margot Burns, Jane B. Cryan, Malak Abedalthagafi, Yun Jee Kang, Nikolaus Schultz, David A. Reardon, Eudocia Q. Lee, Mikael L. Rinne, Andrew D. Norden, Lakshmi Nayak, Sandra Ruland, Lisa M. Doherty, Debra C. LaFrankie, Margaret Horvath, Ayal A. Aizer, Andrea Russo, Nils D. Arvold, Elizabeth B. Claus, Ossama Al-Mefty, Mark D. Johnson, Alexandra J. Golby, Ian F. Dunn, E. Antonio Chiocca, Lorenzo Trippa, Sandro Santagata, Rebecca D. Folkerth, Philip Kantoff, Barrett J. Rollins, Neal I. Lindeman, Patrick Y. Wen, Azra H. Ligon, Rameen Beroukhim, Brian M. Alexander, Keith L. Ligon
Journal: Neuro-Oncology (2015)

Multidimensional genotyping of formalin-fixed paraffin-embedded (FFPE) samples has the potential to improve diagnostics and clinical trials for brain tumors, but prospective use in the clinical setting is not yet routine. We report our experience with implementing a multiplexed copy number and mutation-testing program in a diagnostic laboratory certified by the Clinical Laboratory Improvement Amendments. We collected and analyzed clinical testing results from whole-genome array comparative genomic hybridization (OncoCopy) of 420 brain tumors, including 148 glioblastomas. Mass spectrometry–based mutation genotyping (OncoMap, 471 mutations) was performed on 86 glioblastomas. OncoCopy was successful in 99% of samples for which sufficient DNA was obtained (n = 415). All clinically relevant loci for glioblastomas were detected, including amplifications (EGFR, PDGFRA, MET) and deletions (EGFRvIII, PTEN, 1p/19q). Glioblastoma patients ≤40 years old had distinct profiles compared with patients >40 years. OncoMap testing reliably identified mutations in IDH1, TP53, and PTEN. Seventy-seven glioblastoma patients enrolled on trials, of whom 51% participated in targeted therapeutic trials where multiplex data informed eligibility or outcomes. Data integration identified patients with complete tumor suppressor inactivation, albeit rarely (5% of patients) due to lack of whole-gene coverage in OncoMap. Combined use of multiplexed copy number and mutation detection from FFPE samples in the clinical setting can efficiently replace singleton tests for clinical diagnosis and prognosis in most settings. Our results support incorporation of these assays into clinical trials as integral biomarkers and their potential to impact interpretation of results. Limited tumor suppressor variant capture by targeted genotyping highlights the need for whole-gene sequencing in glioblastoma.
Book: Pox: Genius, Madness, and the Mysteries of Syphilis
Authors: Gavin Yamey
Journal: BMJ (2003)

At the end of the 19th century the syphilis expert Alfred Fournier estimated that 15% of the population of Paris was infected with syphilis. There was probably a similar prevalence in big cities across Europe and the United States. And yet, as Deborah Hayden notes in her introduction to Pox, there are almost no memoirs or biographies by or about people who had syphilis during this era. Syphilis, she writes, “was life's dark secret.”




Figure 1



Deborah Hayden

Basic Books, £20.99, pp 379 ISBN 0 465 02881 0

Rating: ★★★★




Pox is Hayden's ambitious attempt to shine some light on this darkness. She argues that although syphilis is rarely explicitly mentioned in the memoirs, biographies, or even the medical records of famous 19th and 20th century figures, if you are alert to the right clues, you can make a convincing case for a diagnosis.

Hayden's detective work leads her to some pretty explosive conclusions. Oscar Wilde's Portrait of Dorian Gray was a secret parable for Wilde's struggle with syphilis. Vincent Van Gogh started painting images of death in 1886 after contracting syphilis. James Joyce had the pox. And Hitler's life story and behaviour only really make sense in the context of his syphilis, which he may have contracted from a Jewish prostitute.

It is almost impossible, of course, for any syphilis detective like Hayden to prove that a historical figure had the disease, since a posthumous tissue sample is rarely available for testing. Hayden admits that retrospective diagnosis is a fragile art. All she is able to do is to gather a body of circumstantial evidence to support the diagnosis from the records of her subjects' lives.

Because of the stigma attached to the illness, and out of a desire to protect the subject's reputation, these records rarely, if ever, mention the word syphilis. What Hayden manages to do so wonderfully is to find recurrent patterns of symptoms and behaviours in her subjects' lives that are best explained by syphilis.

The typical pattern that she finds begins with high risk sexual behaviour. There is fever and malaise, then some form of medical treatment, such as mercury, arsenic, or potassium iodide, followed by a long list of progressive pains and ailments. Later in the subject's life, there are unusual emotional and behavioural disturbances that can include mania, euphoria, depression, and hallucinations. There may also be physical signs, like changes in handwriting, tremors, eye signs, and heart murmurs. Death may be preceded by a period of dementia or psychosis.

Again and again Hayden finds this pattern. Like all great whodunnit stories, she builds clue upon clue until the reader is convinced that it was syphilis that done it. Fortunately, she goes beyond simply explaining away her subjects' lives as being merely a byproduct of their secret infection. Instead, she uses syphilis as another lens through which we should view the complicated genius, madness, and creativity of some of the most influential figures of the past 200 years.
Technical ability to treat male factor infertility must not overtake academic knowledge
Authors: M R. Gazvani, D. H Richmond, P. J Howard, C. R Kingsland, D I. Lewis-Jones
Journal: BMJ (1998)

EDITOR—We were alarmed by Kurinczuk et al's findings that infants born after intracytoplasmic sperm injection are twice as likely as other infants to have a major birth defect and nearly 50% more likely to have a minor defect.1 Our unit has been concerned about the safety of intracytoplasmic sperm injection,2 and this concern has been voiced by other units. We previously suggested that routine karyotyping should …
Fibrinolytic Agents in Surgical Practice
Authors: William G. Anlyan
Journal: JAMA (1961)

The role of non-toxic purified preparations of human fibrinolysin as an adjunct to the surgical treatment of thromboembolic disease was evaluated in 37 patients. In each case surgical intervention was carried out in response to the usual indications; in addition, each patient received a preparation of fibrinolysin by venoclysis. In many cases the subjective evidence of improvement was corroborated by objective evidence in the form of arteriograms or the return of arterial pulses. The failures included patients with old organized emboli or with thromboses that had existed longer, than 48 hours. The optimum duration of fibrinolysin therapy was estimated to be about 30 hours. In order to prevent rethrombosis it was necessary to maintain the patient subsequently on heparin therapy.
Antagonism of selectin function attenuates microvascular platelet deposition and platelet-mediated myocardial injury after transient ischemia
Authors: José A. Barrabés, David Garcia-Dorado, Maribel Mirabet, Javier Inserte, Luis Agulló, Bernat Soriano, Anna Massaguer, Ferran Padilla, Rosa-Maria Lidón, Jordi Soler-Soler
Journal: Journal of the American College of Cardiology (2005)
Penicilloyl-Polylysine Skin Test:
Authors: Sorrel S. Resnik
Journal: JAMA (1966)

THE PRESENT report documents the view that intradermal skin testing with the synthetic polyfunctional hapten of penicillin, ie, penicilloylpolylysine (PPL), poses the hazard of anaphylaxis. In addition, it illustrates the fact that antigen specificity may remain in such a narrow band that the PPL skin test fails to indicate what the patient's reaction to penicillin G may be. Admittedly unusual, the following experience has been extracted from our investigations of adverse drug reactions. 1   Report of a Case  This 30-year-old, healthy, white man gave a history of having developed a delayed papular eruption following potassium penicillin G therapy six years ago. Treatment with penicillin had been avoided in the interim. The following observations were made: Absolute circulating basophil count was 29/cu mm (normal range = 20 to 50). Results from a penicillin G direct basophil test 2 (dilution 1/600) were negative. Results from the penicillin G histamine release test (indirect rabbit)
Role of cardiac ATP-regulated potassium channels in differential responses of endocardial and epicardial cells to ischemia.
Authors: T Furukawa, S Kimura, N Furukawa, A L Bassett, R J Myerburg
Journal: Circulation Research (1991)

Epicardial cells are more susceptible to the electrophysiological effects of ischemia than are endocardial cells. To explore the ionic basis for the differential electrophysiological responses to ischemia at the two sites, we used patch-clamp techniques to study the effects of ATP depletion on action potential duration and the ability of ATP-regulated K+ channels in single cells isolated from feline left ventricular endocardial and epicardial surfaces. During ATP depletion by treatment with 1 mM cyanide (CN-), shortening of action potential durations was significantly greater in epicardial cells than in endocardial cells. Thirty minutes after initiating exposure to 1 mM CN-, action potential duration at 90% repolarization was reduced to 0.70 +/- 0.12 of the control value for endocardial cells versus 0.39 +/- 0.18 for epicardial cells (p less than 0.01), and action potential duration at 20% repolarization was reduced to 0.72 +/- 0.13 for endocardial cells versus 0.12 +/- 0.09 for epicardial cells (p less than 0.01). In both endocardial and epicardial cells, the shortening of action potential by CN- treatment was partially reversed by 0.3 microM glibenclamide; the magnitude of reversal, however, was much greater in epicardial cells. After exposure to 1 mM CN-, the activity of ATP-regulated K+ channels in cell-attached membrane patches was significantly greater in epicardial cells than in endocardial cells. To study the dose-response relation between ATP concentration and open-state probability of the channels, intracellular surfaces of inside-out membrane patches containing ATP-regulated K+ channels were exposed to various concentrations of ATP (10-1,000 microM). The concentration of ATP that produced half-maximal inhibition of the channel was 23.6 +/- 21.9 microM in endocardial cells and 97.6 +/- 48.1 microM in epicardial cells (p less than 0.01). These data indicate that ATP-regulated K+ channels are activated by a smaller reduction in intracellular ATP in epicardial cells than in endocardial cells. The differential ATP sensitivity of ATP-regulated K+ channels in endocardial and epicardial cells may be responsible for the differential shortening in action potentials during ischemia at the two sites.
Is a European healthcare policy emerging?
Authors: E. Mossialos, M. McKee
Journal: BMJ (2001)

In 1998 two rulings by the European Court of Justice caused alarm in health ministries across Europe. 1 2 Until then governments and insurance funds had believed that they had the right to decide whether they would pay for non-urgent treatment carried out abroad. Free movement of people within the European Union necessitates the provision of emergency care and also allows health authorities to send patients abroad for treatment not available in their own country. However, the authorities had to authorise this in advance.3 Now a further ruling by the court has brought some additional clarity but still leaves many questions unresolved.4

The 1998 rulings involved two citizens of Luxembourg. Mr Decker, who had obtained spectacles, and Mr Kohll, who underwent orthodontic treatment, argued successfully that they should be reimbursed by the Luxembourg health insurance fund even though it had not authorised their treatment abroad.5

One element of the Kohll …
Taurine and Vitamin C Modify Monocyte and Endothelial Dysfunction in Young Smokers
Authors: F.M. Fennessy, D.S. Moneley, J.H. Wang, C.J. Kelly, D.J. Bouchier-Hayes
Journal: Circulation (2003)

Background— Endothelial dysfunction initiated by monocyte-endothelial interactions has previously been observed in many vasculopathies, including chronic cigarette smoking. Taurine, a semiessential amino acid, and vitamin C, a naturally occurring antioxidant, have previously been shown to have endothelial protective effects when exposed to proinflammatory insults. Therefore, we hypothesized that taurine and vitamin C would restore endothelial function in young smokers by modifying monocyte-endothelial interactions. Methods and Results— Endothelial-dependent vasodilatation was assessed in vivo using duplex ultrasonography, and monocyte-endothelial interactions were assessed in vitro using endothelial cell culture (human umbilical vein endothelial cells [HUVECs]) with monocyte-conditioned medium (MCM). Endothelial-dependent vasodilatation was significantly impaired in young smokers compared with nonsmokers. Pretreatment of young smokers for 5 days with 2 g/d vitamin C and, more significantly, with 1.5 g/d taurine attenuated this response. MCM taken from smokers impaired the release of nitric oxide and increased the levels of endothelin-1 release from HUVECs. When HUVECs were cultured with MCM from smokers who had been treated with taurine, the levels of nitric oxide and endothelin-1 returned toward control levels. This was attributed to an upregulation in endothelial nitric oxide synthase expression. Conclusions— These observations suggest that taurine supplementation has a beneficial impact on macrovascular endothelial function, and an investigation of its effect on altered endothelial function in dyslipidemic states is warranted.
Case of Diphtheria Saved by Tracheotomy
Authors: G. Buchanan
Journal: BMJ (1867)

BRITISH MEDICAL JORKAL.2,1.will not be contended in these pages that any change of foe, nervous or otherwise, can be manifested in an unchanged material organ; but the changes in the prolonged shock are probably similar in cha- racter to those which occur in the more rapidly fatal forms.
LIPOMA OF THE LABIUM MAJUS.
Authors: HENRY MARSHALL FENNO
Journal: JAMA (1899)

Kelly, in his excellent work on "Operative Gynecology," says that lipoma or fatty tumor is one of the rarest gynecologic affections; no writer has yet recorded more than a single instance in his own practice. Dr. Boldt, in Keating and Coe's "Clinical Gynecology," speaks of a case where he removed a lipoma weighing ten ounces which was attached to the left labium majus by a pedicle two inches long; he says that the tumor was not altogether of fat tissue, the lobules of the latter being enveloped with a fibrous connective tissue; hence the designation "fibroli poma." Kelly says of a case which he saw in the Episcopal Hospital, Philadelphia, that an ovoid tumor, three inches long, hung from the middle of the right labium majus by a slender pedicle two inches in length. My own case was a mulatto girl, Sylvia A. C., 28 years of age, married, having
SOME HERNIAS THAT DISQUALIFY FOR MILITARY SERVICE, WHETHER OPERATED ON OR NOT
Authors: JOSEPH COLT BLOODGOOD
Journal: JAMA (1918)

into the buttocks, the improvement being gradual.In this case intramuscular injections of 20 c.c. of the noncitrated paternal blood had been of no avail, but the injection of between 150 and 200 c.c. of citrated paternal blood in the longitudinal sinus was followed by immediate improvement.
ET-27 * REPLICATION AND SPREAD OF ONCOLYTIC HERPES VIRUS IN GLIOMA STEM CELLS CAN BE ENHANCED BY SPECIFIC INHIBITION OF HISTONE DEACETYLASE 6
Authors: J. K. Kaufmann, H. Nakashima, T. Nguyen, P.-Y. Wang, I. Nakano, T. P. Cripe, E. A. Chiocca
Journal: Neuro-Oncology (2014)

High-grade gliomas remain clinically challenging and under current therapies the prognosis is generally dismal. Intratumoral heterogeneity, therapy resistance, and tumor recurrence likely caused by glioma stem cells (GSCs) still represent major challenges, which need to be addresses by novel, multimodal therapies. We attempted to combine rQnestin34.5, an oncolytic herpes simplex virus expressing its ICP34.5 virulence gene under the glioma-specific nestin promoter, with specific inhibition of histone deacetylase 6 (HDAC6). We have previously reported that pan-HDAC inhibition using valproic acid enhances rQnestin34.5's antitumor activity and our data obtained in established glioma cell lines indicate that sole inhibition of HDAC6 can at least in part be accounted for this effect. We now analyzed the influence of the specific HDAC6 inhibitor Tubacin on rQnestin34.5 replication in GSC lines originating from proneural, classic, and mesenchymal glioma subtypes. Time-lapse microscopy revealed that plaque formation and spread were accelerated within the first 48 hours after infection when cells were pre-treated with Tubacin, translating into significantly increased cytotoxicity in the respective time frame. Viral DNA replication was enhanced after combination treatment as increased viral copy numbers per cell were detected by qPCR. Furthermore, HDAC6 inhibition increased mRNA expression levels of immediate early and late genes. Importantly, the positive effect of Tubacin on rQnestin34.5 replication and spread in GSCs was critically dependent on drug pre-treatment regimens and very low infectious titers. We also noted that the benefit of rQnestin34.5 oncolysis from HDAC6 inhibition varied quantitatively between GSCs. While responsiveness was not determined by glioma subtype or HDAC6 expression levels, we are currently investigating whether the choice of the exact viral entry mechanism can be used as a predictive marker. Future studies will also aim at establishing a therapeutic regimen demonstrating the potential benefit of HDAC6 inhibition in addition to herpes simplex oncolysis in a GSC-derived orthotopic glioma model.
Role of residual insulin secretion in protecting against ketoacidosis in insulin-dependent diabetes.
Authors: S Madsbad, K G Alberti, C Binder, J M Burrin, O K Faber, T Krarup, L Regeur
Journal: BMJ (1979)

The role of preserved beta-cell function in preventing ketoacidosis in type I insulin-dependent diabetes was assessed in eight patients with and seven patients without residual beta-cell function as determined from C-peptide concentrations. After 12 hours of insulin fatty-acid, and glycerol concentrations were all significantly higher in patients without beta-cell function than in those with residual secretion. Mean blood glucose concentrations reached 17.2 +/- SE of mean 1.3 mmol/l (310 +/- 23 mg/100 ml) in the first group compared with 8.8 +/- 1.4 mmol/l (159 +/- 25 mg/100 ml) in the second (P less than 0.01), while 3-hydroxybutyrate concentrations rose to 5.5 +/- mmol/l (57 +/- 5 mg/100 ml) and 1.4 +/- 0.3 mmol/l (15 +/- 3 mg/100 ml) in the two groups respectively (P less than 0.01). Individual mean C-peptide concentrations showed a significant inverse correlation with the final blood glucose values (r = -0.91; P less than 0.02). These findings strongly suggest that even minimal residual insulin secretion is important for metabolic wellbeing in diabetes and may prevent the development of severe ketoacidosis when insulin delivery is inadequate.
Prediction of Heart Failure Mortality in Emergent Care
Authors: Douglas S. Lee, Audra Stitt, Peter C. Austin, Therese A. Stukel, Michael J. Schull, Alice Chong, Gary E. Newton, Jacques S. Lee, Jack V. Tu
Journal: Annals of Internal Medicine (2012)

Background: Heart failure contributes to millions of emergency department (ED) visits, but hospitalization-versus-discharge decisions are often not accompanied by prognostic risk quantification. Objective: To derive and validate a model for acute heart failure mortality applicable in the ED. Design: Clinical data abstraction with development of a broadly applicable multivariate risk index for 7-day death using initial vital signs, clinical and presentation features, and readily available laboratory tests. Setting: Multicenter study of 86 hospitals in Ontario, Canada. Patients: Population-based random sample of 12 591 patients presenting to the ED from 2004 to 2007. Measurements: Death within 7 days of presentation. Results: In the derivation cohort (n = 7433; mean age, 75.4 years [SD, 11.4]; 51.5% men), mortality risk increased with higher triage heart rate (adjusted odds ratio [OR], 1.15 [95% CI, 1.03 to 1.30] per 10 beats/min) and creatinine concentration (OR, 1.35 [CI, 1.14 to 1.60] per 1 mg/dL [88.4 µmol/L]), and lower triage systolic blood pressure (OR, 1.52 [CI, 1.31 to 1.77] per 20 mm Hg) and initial oxygen saturation (OR, 1.16 [CI, 1.01 to 1.33] per 5%). Nonnormal serum troponin levels (OR, 2.75 [CI, 1.86 to 4.07]) were associated with increased mortality risk. Areas under the receiver-operating characteristic curves of the multivariate model were 0.805 for the derivation data set (bootstrap-corrected, 0.811) and 0.826 for validation data set (n = 5158; mean age, 75.7 years [SD, 11.4]; 51.6% men). In the derivation cohort, a multivariate index score stratified 7-day mortality with rates of 0.3%, 0.3%, 0.7%, and 1.9% in quintiles 1 to 4, respectively. Mortality rates in the 2 highest risk groups were 3.5% and 8.2% in deciles 9 and 10, respectively. Limitation: Left ventricular ejection fraction was not included in the model. Conclusion: A multivariate index comprising routinely collected variables stratified mortality risk with high discrimination in a broad group of patients with acute heart failure presenting to the ED. Primary Funding Source: Canadian Institutes of Health Research.
Parameningeal rhabdomyosarcoma in pediatric age: results of a pooled analysis from North American and European cooperative groups
Authors: J.H.M. Merks, G.L. De Salvo, C. Bergeron, G. Bisogno, A. De Paoli, A. Ferrari, A. Rey, O. Oberlin, M.C.G. Stevens, A. Kelsey, J. Michalski, D.S. Hawkins, J.R. Anderson
Journal: Annals of Oncology (2013)