tbuckley/cabot-search huggingface dataset:
Dermatomyositis Induced by Anti–Tumor Necrosis Factor in a Patient With Juvenile Idiopathic Arthritis
Authors: Stephanie W. Liu, Nicole F. Velez, Christina Lam, Alisa Femia, Scott R. Granter, Henry B. Townsend, Ruth Ann Vleugels
Journal: JAMA Dermatology (2013)

Biologic therapies, including anti-tumor necrosis factor (TNF) agents, are increasingly used to treat a variety of autoimmune diseases. Paradoxically, these agents have been reported to induce some of the very diseases they were designed to treat, including dermatomyositis (DM). We describe the first case of anti-TNF-associated DM without muscle involvement presenting in an adult patient with a history of arthritis since childhood. This cutaneous eruption recurred after rechallenge with an alternate anti-TNF agent.A 46-year-old man with juvenile idiopathic arthritis developed a pruritic cutaneous eruption while receiving etanercept. Given concern about a drug-induced eruption, etanercept therapy was discontinued and the cutaneous findings improved. However, after rechallenge with adalimumab, he developed similar findings consistent with the skin manifestations of DM. After discontinuation of all anti-TNF drug therapy and the addition of methotrexate sodium, his eruption improved.Because the use of these agents is increasing, practitioners should be aware of the possibility of anti-TNF-induced autoimmune disorders, including DM. The case described herein is unique in that anti-TNF-induced autoimmune disease occurred in a patient with existing arthritis since childhood and recurred with rechallenge, adding further evidence to support the existence of anti-TNF-induced DM.
Introducing the postoperative care team
Authors: D. R Goldhill
Journal: BMJ (1997)

The 1992-3 and 1993-4 national confidential enquiries into perioperative deaths1 2 record the use of monitoring, the availability of facilities, and the experience of the doctors caring for patients. About two thirds of patients died three or more days after surgery, with most of the deaths taking place on a ward. A high percentage of those who died had had a cardiac or respiratory complication, renal failure, or infection, and some of these complications might have been preventable.

Preoperative preparation and a high standard of anaesthetic care are essential, as they affect postoperative events.3 4 By the end of surgery it may be too late to substantially alter outcome for some patients.5 On the other hand, aggressive postoperative optimisation of physiological values has been shown to decrease mortality and morbidity in …
671. Nerve Growth Factor and Neurotrophin-3 Delivered by HSV Gene Transfer Reverses Diabetic Neuropathy
Authors: James R. Goss, Munmun Chattopadhyay, William F. Goins, Darren Wolfe, Marina Mata, Joseph C. Glorioso, David J. Fink
Journal: Molecular Therapy (2005)

Top of pageAbstract
Peripheral neuropathy, involving motor, sensory, and autonomic nerves, is a common and debilitating complication of diabetes. Many features of human diabetic neuropathy can be modeled in the mouse using streptozotocin (STZ) to selectively destroy pancreatic beta cells resulting in sustained hyperglycemia but not requiring insulin replacement. We have previously demonstrated that recombinant replication defective herpes simplex virus (HSV)-based vectors expressing the neurotrophic proteins NGF (vector SHN) or NT3 (vector QL2HNT3) delivered by subcutaneous inoculation to transduce dorsal root ganglia prevents the development of neuropathy in the STZ mouse. Using a double-blind experiment, we have extended these findings by examining if these vectors could reverse STZ-induced neuropathy once it has been established. Male Swiss-Webster mice were injected with streptozotocin (STZ) and six weeks later the presence of peripheral neuropathy was confirmed by electrophysiological measurements of a foot sensory nerve response to an evoked potential and the foot withdrawal latency from a heat source. STZ-treated mice were then randomized to four treatment groups: 1) No vector; 2) vector SHZ (control vector); 3) vector SHN; or, 4) vector QL2HNT3. Mice injected with STZ developed a peripheral neuropathy characterized by a decrease in the foot nerve sensory amplitude, an increase in the foot withdrawal latency from a heat source, and a decrease in the number of nerve fibers innervating the skin of the hind foot. These indices of neuropathy were reversed 5 weeks after mice were inoculated with either SHN or QL2HNT3 into the hind foot; mice inoculated with a control vector (SHZ) demonstrated no improvement. This data suggests that neurotrophic factor gene transfer using HSV-based vectors was able to reverse functional measures of established peripheral neuropathy in diabetic rodents and provides further evidence for the potential of HSV-based gene therapy to treat human diabetic neuropathy.
Gastrointestinal manifestations of HIV infection
Authors: D Sharpstone, B Gazzard
Journal: The Lancet (1996)

SummaryThe harrowing picture of emaciated terminally ill AIDS patients is a reminder of our lack of understanding of immunological mechanisms that normally control opportunistic infections. Many gastrointestinal pathogens in patients with AIDS are resistant to treatment and lead inexorably to weight loss and death. Although knowledge of the pathogenesis and clinical significance of weight loss has improved considerably, this has not yet led to a sustained effort to improve nutritional status during early stages of disease.
Organ blood flow and somatosensory-evoked potentials during and after cardiopulmonary resuscitation with epinephrine or phenylephrine.
Authors: C L Schleien, R C Koehler, H Gervais, I D Berkowitz, J M Dean, J R Michael, M C Rogers, R J Traystman
Journal: Circulation (1989)

Pure alpha-adrenergic agonists, such as phenylephrine, and mixed alpha- and beta-adrenergic agonists, such as epinephrine, raise perfusion pressure for heart and brain during cardiopulmonary resuscitation (CPR). However, with the high doses used during CPR, these drugs may directly affect vascular smooth muscle and metabolism in brain and heart. We determined whether at equivalent perfusion pressure, continuous infusion of phenylephrine (20 micrograms/kg/min) or epinephrine (4 micrograms/kg/min) leads to equal organ blood flow, cerebral O2 uptake, and cerebral electrophysiologic function. During 20 minutes of CPR initiated immediately upon ventricular fibrillation in anesthetized dogs, left ventricular blood flow was similar with epinephrine (45 +/- 9 ml/min/100 g) or phenylephrine (47 +/- 8 ml/min/100 g) infusion. The ratio of subendocardial to subepicardial blood flow fell equivalently during CPR with either epinephrine (1.23 +/- 0.06 to 0.70 +/- 0.05) or phenylephrine (1.32 +/- 0.07 to 0.77 +/- 0.05) administration. At similar levels of cerebral perfusion pressure (44 +/- 3 mm Hg), similar levels of cerebral blood flow were measured in both groups (27 +/- 3 ml/min/100 g). Cerebral O2 uptake was maintained at prearrest levels in both groups. Somatosensory-evoked potential amplitude was modestly reduced during CPR, but it promptly recovered after defibrillation. During CPR and at 2 hours after resuscitation, there were no differences between drug groups in the level of regional cerebral or coronary blood flow, cerebral O2 uptake, or evoked potentials. Therefore, with minimal delay in the onset of CPR and with equipotent pressor doses of phenylephrine and epinephrine, we found no evidence that one agent provides superior coronary or cerebral blood flow or that epinephrine by virtue of its beta-adrenergic properties adversely stimulates cerebral metabolism at a critical time that would impair brain electrophysiologic function. Moreover, epinephrine did not preferentially impair subendocardial blood flow as might be expected if it enhanced the strength of fibrillatory contractions.
John Humphreys Hughes
Authors: A. Ap-Thomas
Journal: BMJ (2009)

<h3>Abstract</h3> DNA methylation has been extensively linked to alterations in gene expression, playing a key role in the manifestation of multiple diseases, most notably cancer. For this reason, researchers have long been measuring DNA methylation in living organisms. The relationship between methylation and expression, and between methylation in different genomic regions is of great theoretical interest from a molecular biology perspective. Therefore, several models have been suggested to support the prediction of methylation status in samples. These models, however, have two main limitations: (a) they heavily rely on partially measured methylation levels as input, somewhat defeating the object as one is required to collect measurements from the sample of interest before applying the model; and (b) they are largely based on human mediated feature engineering, thus preventing the model from unveiling its own representations. To address these limitations we used deep learning, with an attention mechanism, to produce a general model that predicts DNA methylation for a given sample in any CpG position based solely on the sample9s gene expression profile and the sequence surrounding the CpG. We show that our model is capable of generalizing to a completely separate test set of CpG positions and subjects. Depending on gene-CpG proximity conditions, our model can attain a Spearman correlation of up to 0.8 and MAE of 0.14 for thousands of CpG sites in the test data. We also identify and analyze several motifs and genes that our model suggests may be linked to methylation activity, such as Nodal and Hand1. Moreover, our approach, and most notably the use of attention mechanisms, offers a novel framework with which to extract valuable insights from gene expression data when combined with sequence information. The code and trained models are available at: https://github.com/YakhiniGroup/Methylation
Treatment of Crotalid Envenomation
Authors: Mahlon Z. Bierly
Journal: JAMA (1966)

Arecent communication, "Treatment of Snakebite,"<sup>1</sup>which recommends "cryotherapy," and claims that "no harm is done to an [envenomated] extremity packed in<i>fresh</i>water ice for... six days in the absence of vascular impairment," warrants some comment, particularly in the light of conflicting published concepts.<sup>2</sup> The communication referred to contains a direct quotation: "The big advantage of cryotherapy is its reversibility. In the temperature range of 15 C to 0 C, tissue temporarily shows all of the physiologic inhibitory effects of freezing without producing permanent destruction." This is lifted, inaccurately, and out of context, from<i>Medical World News</i>of Sept 25, 1964, pp 79-86. The term used in the article in Medical World News is "cryosurgery," not "cryotherapy," the surgeon uses a probe chilled by liquid nitrogen or some other coolant to perform various types of operations. The subsequent sentence is as follows, "This phenomenon allows the surgeon to
Points: Tap water for electrocardiographic recordings
Authors: W E Mahon
Journal: BMJ (1979)

Local governments have multiple options to secure financing for infrastructure projects, including using tax-increment financing (TIF) bonds. Although the TIF concept brings numerous benefits, it is also associated with several key challenges, including characterizing the uncertainty in tax increment revenue as the most prominent challenge. This article presents a framework that aims to help all market stakeholders better understand the credit risk associated with TIF bonds. The framework focuses on reconstituting the asset credit risk profile and detecting early warning signals of changing conditions. The key benefit of the proposed framework is its capacity to use publically available time series data. The case study illustrating the framework is based on the “Uptown Development Authority” bond, structured to support redevelopment projects in Houston, Texas.
Right and left heart size and function in infants with symptomatic coarctation.
Authors: T P Graham, G F Atwood, R C Boerth, R J Boucek, C W Smith
Journal: Circulation (1977)

Right and left heart volumes, ejection fractions and ventricular outputs were determined from biplane cineangiocardiograms in infants with symptomatic coarctation of the aorta and correlated with clinical and hemodynamic alterations. Patients were divided into two age groups: group 1, aged 3.5 to 14 days and group 2, 5 weeks to 7 1/2 months. Infants in group 1 had severe depressions of left ventricular ejection fraction and output associated with normal left ventricular size. The massive cardiomegaly in these infants results from right heart enlargement secondary to left-to-right atrial shunting, and pulmonary hypertensive right heart failure, and possibly a more distensible right than left ventricle. Infants in group 2 also have right, and to a lesser degree, left heart enlargement. Group 2 patients differ from group 1 infants in having less impairment of left heart pump function and significant left ventricular myocardial hypertrophy. Echocardiographic measurements of left ventricular pump function are normal or increased in postoperative patients. Thus alterations of left ventricular function in infants with symptomatic coarctation appear to be largely afterload related and do not indicate permanent impairment of left ventricular contractile function.
Cholestatic jaundice due to terbinafine
Authors: C.M Dwyer, M.I White, T.S Sinclair
Journal: British Journal of Dermatology (1997)

Journal Article Cholestatic jaundice due to terbinafine Get access C.M Dwyer, C.M Dwyer Departments of Dermatology Aberdeen Royal Hospital NHS Trust. Foresterhill. Aberdeen AB9 2ZB. U.K. Search for other works by this author on: Oxford Academic Google Scholar M.I White, M.I White Departments of Dermatology Aberdeen Royal Hospital NHS Trust. Foresterhill. Aberdeen AB9 2ZB. U.K. Search for other works by this author on: Oxford Academic Google Scholar T.S Sinclair T.S Sinclair Departments of Dermatology Gastroenterology. Aberdeen Royal Hospital NHS Trust. Foresterhill. Aberdeen AB9 2ZB. U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 136, Issue 6, 1 June 1997, Pages 976–977, https://doi.org/10.1111/j.1365-2133.1997.tb03954.x Published: 01 June 1997
Effects of Lovastatin and Pravastatin on Coronary Artery Disease
Authors: Mark R. Goldstein
Journal: Annals of Internal Medicine (1994)

Letters1 May 1994Effects of Lovastatin and Pravastatin on Coronary Artery DiseaseMark R. Goldstein, MDMark R. Goldstein, MDCrozer-Chester Medical Center; Upland, PA 19013Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-9-199405010-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In comparing the Monitored Atherosclerosis Regression Study (MARS) [1] with another recently published coronary prevention trial that also tested reductase inhibitors against placebo, it appears that a decreased coronary event rate may be related to the particular reductase inhibitor.The MARS trial was a randomized, double-blind, placebo-controlled, multicenter angiographic trial testing the effects of lovastatin on the progression of coronary artery disease in patients with angiographically proven coronary disease. Most patients had multiple risk factors for the disease. Treatment with diet and lovastatin (80 mg/d) for 2.2 years had a favorable effect on lipoprotein levels and angiographically ...References1. Blankenhorn DH, Azen SP, Kramsch DM, Mack WJ, Cashin-Hemphill L, Hodis HN, et al. Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS). Ann Intern Med. 1993; 119:969-76. Google Scholar2. Effects of pravastatin in patients with serum total cholesterol levels from 5.2 to 7.8 mmol/liter (200 to 300 mg/dL) plus two additional atherosclerotic risk factors. The Pravastatin Multinational Study Group for Cardiac Risk Patients. Am J Cardiol. 1993; 72:1031-7. Google Scholar3. Jungnickel PW, Cantral KA, Maloley PA. Pravastatin: a new drug for the treatment of hypercholesterolemia. Clin Pharm. 1992; 11:677-89. Google Scholar Author, Article, and Disclosure InformationAffiliations: Crozer-Chester Medical Center; Upland, PA 19013 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByLong-term Clinical Outcomes of Statin Use for Chronic Heart Failure: A Meta-analysis of 15 Prospective StudiesLovastatin and sudden unexpected death in epilepsy: A matter for debateEffects of Statin Treatment on Cardiac Function in Patients With Chronic Heart Failure: A Meta-Analysis of Randomized Controlled TrialsLovastatin reduces neuronal cell death in hippocampal CA1 subfield after pilocarpine-induced status epilepticus: preliminary results 1 May 1994Volume 120, Issue 9Page: 811-812KeywordsCholesterolCoronary arteriesDietLipoproteinsMedical risk factorsMyocardial infarctionPercutaneous transluminal coronary angioplastyStable coronary artery diseaseSurgeryUnstable angina Issue Published: 1 May 1994 CopyrightCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract P4-12-22: Time to relapse (TTR) is a potential discriminator of clinical outcome in HER2-positive breast cancer (BC) patients (pts) progressing on adjuvant trastuzumab (AdjT)
Authors: S Di Cosimo, D Serpico, L Porcu, G Fanetti, L Molino, V Torri, F de Braud
Journal: Cancer Research (2013)

Abstract Background: Clinical trials for HER2-positive metastatic BC excluded pts with prior AdjT and/or relapsing within 1 year (yr) from the end of AdjT. With this gap in mind, we aimed to address the presentation, the therapeutic options, and the clinical outcome of BC pts after failure to AdjT. Methods: Medical charts of BC pts relapsing on AdjT and admitted at the National Cancer Institute of Milan were reviewed. Fisher's exact test was used for contingency tables, long-rank test for survival distribution; p&amp;lt;0.05 was considered statistically significant. Data were matched with literature. Results: Forty pts were identified in the 2013 first quarter. Median age at relapse was 49 (26-80) yrs; 67.5% of pts had stage III; 93% neo-/adjuvant anthracycline+/-taxane; 55% hormonotherapy. Median TTR was 23.5 (5.2-108.5) months (mos). Relapses occurred during (early) or after (late) AdjT in 12 (30%) and 28 (70%) pts. Median AdjT cycles were 15 (2-18) and 18 (6-19) in pts with early and late relapses. Early and late relapses shared a similar distribution of hormone receptor positive and negative status (35% vs 25%, p = 0.73). Lung (8% vs 36%, p = 0.12), bone (25% vs 36%, p = 0.72) and multiple (8% vs 36%, p = 0.12) metastases were less likely to occur in pts with early than in late relapses; liver was affected by 42% and 29% of early and late relapses (p = 0.48). T was the 1stline tretament in 77.5% of pts. After a median follow-up of 21.3 (0.6-98.6) mos, 29 pts (72.5%) progressed. Median Time To Progression (TTP) was 12.7 (9.0-15.3) mos, with a response rate (RR) of 61%. Pts relapsing during AdjT had a shorter TTP than pts relapsing after AdjT, 9.2 (95%CI:3.9-13.3) vs 15 mos (95%CI:9.1-27.9), p = 0.048. T was the 2ndline treatment in 65.5% of pts; with a RR 51%. The literature review showed that pts with prior AdjT represent 0.9-11.7% of overall study-population in just 5 of 8 registrational trials in HER2-positive metastatic BC. No trials included pts relapsing during AdjT. Compared to pts from clinical practice, pts of the above trials were less likely to have locally-advanced BC at diagnosis and neo-/adj chemotherapy. Conclusions: T was the choice in both 1st and 2ndline treatment of pts relapsing on AdjT. Anti-tumor activity was consistent accross lines and with literature. These data should be interpreted with caution, as the cross-sectional design may have favored the inclusion of pts at good prognosis. Notwithstanding the above, pts with early relapse to AdjT showed a worse outcome as compared to the rest. Further investigation to tailor therapy for these pts is recommended. Patient data collection continues and an update will be presented at the meeting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-22.
Colombia: the winner takes all
Authors: H. Veeken
Journal: BMJ (1998)

“At least here I can go to sleep knowing I will wake up next day,” says Carlos. We have just climbed the garbage dump of the city of Carthagena. “Look how we live and how we work.” He gestures widely to emphasise the severity of the situation. On one side of the dump we see the shanty town Nelson Mandela, on the other people are sorting their way through freshly unloaded garbage. Lorries come and go. We are forced to breathe through our mouths; the smell is offensive. “I left my house because of violence,” Carlos tells me as we stroll back to the settlement. “How could I possibly stay when I was threatened? I had a shop and land—I was reasonably well off. I was accused of supporting guerrillas, and it was better to go. There is killing every day; they do not hesitate. I have seen too many people killed. I have nothing, and I might be hungry every now and then, but I am alive.”

#### Summary points

The Nelson Mandela settlement has been in existence for two years, and still new people arrive. There is no shade anywhere. The people erect makeshift huts of plastic and wood. The sun beats down on the plastic—the only protection against the heat and rain— making it toxic.

We speak to a couple who arrived three months ago. “We survive, but no more than that,” the man tells us. “I earn 5000 pesos (£2.45) a day by selling chips in town, but there …
T-Cell–Mediated Lysis of Endothelial Cells in Acute Coronary Syndromes
Authors: Takako Nakajima, Stephanie Schulte, Kenneth J. Warrington, Stephen L. Kopecky, Robert L. Frye, Jörg J. Goronzy, Cornelia M. Weyand
Journal: Circulation (2002)

CD4 T lymphocytes accumulate in unstable plaque. The direct and indirect involvement of these T cells in tissue injury and plaque instability is not understood.Gene profiling identified perforin, CD161, and members of the killer-cell immunoglobulin-like receptors as being differentially expressed in CD4(+)CD28(null) T cells, a T-cell subset that preferentially infiltrates unstable plaque. Frequencies of CD161(+) and perforin-expressing CD4 T cells in peripheral blood were significantly increased in patients with unstable angina (UA). CD161 appeared on CD4(+)CD28(null) T cells after stimulation, suggesting spontaneous activation of circulating CD4 T cells in UA. Perforin-expressing CD4(+) T-cell clones from patients with UA exhibited cytotoxic activity against human umbilical vein endothelial cells (HUVECs) in redirected cytotoxicity assays after T-cell receptor triggering and also after stimulation of major histocompatibility complex class I-recognizing killer-cell immunoglobulin-like receptors. HUVEC cytolysis was dependent on granule exocytosis, as demonstrated by the paralyzing effect of pretreating CD4(+)CD28(null) T cells with strontium. Incubation of HUVECs with C-reactive protein (CRP) increased HUVEC lysis in a dose-dependent fashion.In patients with UA, CD4 T cells undergo a change in functional profile and acquire cytotoxic capability. Cytotoxic CD4 T cells effectively kill endothelial cells; CRP sensitizes endothelial cells to the cytotoxic process. We propose that T-cell-mediated endothelial cell injury is a novel pathway of tissue damage that contributes to plaque destabilization. The sensitizing effect of CRP suggests synergy between dysregulated T-cell function and acute phase proteins in acute coronary syndromes.