tbuckley/cabot-search huggingface dataset:
Neglected Tropical Skin Diseases
Authors: Peter J. Hotez, Rosannah M. Velasquez, John E. Wolf
Journal: JAMA Dermatology (2014)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Dermatology journal
Mechanism of Aortic Balloon Valvuloplasty: Fracture of Valvular Calcific Deposits
Authors: JEFFREY M. ISNER
Journal: Annals of Internal Medicine (1988)

Balloon valvuloplasty has been shown to acutely reduce the hemodynamic and symptomatic severity of calcific aortic stenosis. The mechanism by which this improvement is accomplished is not known. At necropsy, three patients who died after hemodynamically successful aortic balloon valvuloplasty were found to have aortic valve calcific deposits fractured at one or more sites. These findings suggest that fracture of leaflet calcium represents the basis for successful aortic balloon valvuloplasty.
High-Density Lipoprotein
Authors: Thomas F. Lüscher, Ulf Landmesser, Arnold von Eckardstein, Alan M. Fogelman
Journal: Circulation Research (2014)

High-density lipoprotein (HDL) is a complex mixture of lipoproteins that is associated with many minor proteins and lipids that influence the function of HDL. Although HDL is a promising marker and potential therapeutic target based on its epidemiological data and the effects of healthy HDL in vitro in endothelial cells and macrophages, as well as based on infusion studies of reconstituted HDL in patients with hypercholesterolemia, it remains still uncertain whether or not HDL cholesterol–raising drugs will improve outcomes. Recent studies suggest that HDL becomes modified in patients with coronary artery disease or acute coronary syndrome because of oxidative processes that result in alterations in its proteome composition (proteome remodelling) leading to HDL dysfunction.
Effects of a drug overdose in a television drama on knowledge of specific dangers of self poisoning: population based surveys
Authors: S. O'Connor, J. J Deeks, K. Hawton, S. Simkin, A. Keen, D. G Altman, G. Philo, C. Bulstrode
Journal: BMJ (1999)

Paracetamol is the drug most commonly taken in overdose in the United Kingdom,1causing a substantial number of deaths.2 We have investigated the impact of the fictional portrayal of a potentially fatal paracetamol overdose in the television drama Casualty (seen by 12.8 million viewers) on short and long term knowledge related to paracetamol poisoning.

View this table:

Responses to questionnaire for patients presenting with overdoses in the three weeks before and the three weeks after broadcast of index Casualty episode. Values are numbers (percentages) of those who responded to question unless stated otherwise



The episode (described in detail in accompanying article3) depicted a man suffering potentially fatal liver damage after an untreated paracetamol overdose. Although the particular dose (50 tablets) and delay before presentation (2 days) were mentioned, the episode did not specify minimal toxic doses or maximum safe delays.

At one week and 32 weeks after this episode …
Modulation of cellular immune response against hepatitis C virus nonstructural protein 3 by cationic liposome encapsulated DNA immunization
Authors: Xuanmao Jiao, Richard Y.-H. Wang, Zhiming Feng, Harvey J. Alter, James Wai-Kuo Shih
Journal: Hepatology (2003)

A vaccine strategy directed to increase Th1 cellular immune responses, particularly to hepatitis C virus (HCV) nonstructural protein 3 (NS3), has considerable potential to overcome the infection with HCV. DNA vaccination can induce both humoral and cellular immune responses, but it became apparent that the cellular uptake of naked DNA injected into muscle was not very efficient, as much of the DNA is degraded by interstitial nucleases before it reaches the nucleus for transcription. In this paper, cationic liposomes composed of different cationic lipids, such as dimethyl-dioctadecylammonium bromide (DDAB), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), or 1,2-dioleoyl-sn-glycerol-3-ethylphosphocholine (DOEPC), were used to improve DNA immunization in mice, and their efficiencies were compared. It was found that cationic liposome-mediated DNA immunization induced stronger HCV NS3-specific immune responses than immunization with naked DNA alone. Cationic liposomes composed of DDAB and equimolar of a neutral lipid, egg yolk phosphatidylcholine (EPC), induced the strongest antigen-specific Th1 type immune responses among the cationic liposome investigated, whereas the liposomes composed of 2 cationic lipids, DDAB and DOEPC, induced an antigen-specific Th2 type immune response. All cationic liposomes used in this study triggered high-level, nonspecific IL-12 production in mice, a feature important for the development of maximum Th1 immune responses. In conclusion, the cationic liposome-mediated gene delivery is a viable HCV vaccine strategy that should be further tested in the chimpanzee model.
P66MicroRNA-132/212 family promotes arteriogenesis by prolonging Ras-MAPK signaling
Authors: Z Lei, M M Brandt, A Van Mil, S Grundmann, M Smits, B Van Middelaar, T Fukao, C Cheng, P Doevendans, JPG Sluijter
Journal: Cardiovascular Research (2014)

Arteriogenesis is a complicated process induced by local shear stress caused by local occlusion and is enhanced by growth factors such as VEGF, which is secreted by inflammatory cells and endothelial cells in response to hypoxia. To search for microRNAs involved in arteriogenesis, we performed microarray analysis on hindlimb ischemia mice tissue. We observed a dynamic temporal regulation of microRNAs expression , among which miR-132 /212 were significantly upregulated 4 days after occlusion of femoral artery. The aim of our study was to unravel the role of miR-132/212 in arteriogenesis. In a pericyte-endothelial cell in vitro co-culture assay, overexpression of miR-132/212 in endothelial cells resulted in enhanced neovascularization capacity, including more tubular structures and junctions and longer total tubule length. Inhibition of miR-132/212 decreased total tubule length, and the number of junctions and tubule structures. Ex vivo aorta ring assay demonstrated more branches in wild-type than of miR-132/212 knockout mice. In line with these, microRNA132/212 Knockout mice displayed slower perfusion recovery after hind-limb ischemia than wild type mice. Immunohistochemistry studies further demonstrated that knockout mice have similar number of collateral arteries but they are smaller than wild type. Based on microRNA targets prediction and luciferase assay we found that miR-132/212 enhanced Ras-MAPK signaling by directly inhibiting Rasa1, Spred1, and Spry1 expression which are inhibitors of the Ras-MAPK signaling pathway. In summary, our results show that miR-132/212 promote arteriogenesis by prolonging VEGF initiated Ras-MAPK signaling.
Transcriptional Control of Adipose Lipid Handling by IRF4
Authors: Jun Eguchi, Xun Wang, Songtao Yu, Erin E. Kershaw, Patricia C. Chiu, Joanne Dushay, Jennifer L. Estall, Ulf Klein, Eleftheria Maratos-Flier, Evan D. Rosen
Journal: Cell Metabolism (2011)
Bilirubin Production and Excretion
Authors: Matthew Menken
Journal: JAMA (1966)

The serum bilirubin level represents an equilibrium achieved by a dynamic process of production and excretion. A hyperbilirubinemia that remains constant over a period of time represents an equilibrium at a higher serum level than normal, due either to overproduction of bilirubin from one or more sources with a normal excretion rate, or a decreased rate of excretion with a normal production rate. A rising or falling serum bilirubin, on the other hand, represents an imbalance of production and excretion. A number of the steps in bile pigment production and excretion have now been elucidated. However, in patients with an elevated serum bilirubin concentration the diagnosis is often based on a search for specific ancillary features rather than an understanding of the pathophysiological mechanism involved. Most laboratories, for example, continue to report the plasma bilirubin concentration as the "one-minute" (or "direct-reacting") bilirubin and the "total" bilirubin concentration, even though the
Treating erythema nodosum.
Authors: D Golding
Journal: BMJ (1969)

Primary lateral sclerosis (PLS) is a neurodegenerative disorder of the adult motor system. Characterised by a slowly progressive upper motor neuron syndrome, the diagnosis is clinical, after exclusion of structural, neurodegenerative and metabolic mimics. Differentiation of PLS from upper motor neuron-predominant forms of amyotrophic lateral sclerosis remains a significant challenge in the early symptomatic phase of both disorders, with ongoing debate as to whether they form a clinical and histopathological continuum. Current diagnostic criteria for PLS may be a barrier to therapeutic development, requiring long delays between symptom onset and formal diagnosis. While new technologies sensitive to both upper and lower motor neuron involvement may ultimately resolve controversies in the diagnosis of PLS, we present updated consensus diagnostic criteria with the aim of reducing diagnostic delay, optimising therapeutic trial design and catalysing the development of disease-modifying therapy.
What Dose of Folic Acid Should Be Used for Pregnant Diabetic Women?
Authors: Ismael Capel, Rosa Corcoy
Journal: Diabetes Care (2007)

It is well established that folate requirements increase during pregnancy and that supplementing 0.4 mg folic acid/day to the general pregnant population is beneficial in terms of reducing the risk of neural tube defects (NTDs). Offspring of women with pregestational diabetes mellitus have an increased risk of congenital anomalies, including NTDs (1). In animal models, …
Intranasal calcitonin for the prevention of bone erosion and bone loss in rheumatoid arthritis.
Authors: A Sileghem, P Geusens, J Dequeker
Journal: Annals of the Rheumatic Diseases (1992)

The effect of intranasal salmon calcitonin on pain, erosion progression, and bone loss in 40 women with rheumatoid arthritis was investigated. The study design was double blind, placebo controlled for the first four months and open for the next 36 months, allowing for cross over to active drug treatment or to the control group. Morning stiffness was reduced in the group treated with salmon calcitonin after two and four months. After an average follow up of 28 months no significant effect on erosion progression was observed using the Larsen score. The mean (SD) monthly progressions in the Larsen score in the calcitonin and control groups were 0.21 (0.22) and 0.23 (0.28) respectively. The bone mineral density was evaluated in the forearm and spine. During the 12 months of follow up the control group lost bone at a rate of 2%/year at the spine and 4.8%/year at the radius distal third. In contrast, the group receiving nasal calcitonin gained 1% in bone mineral density at the lumbar spine and no loss at the radius distal third. The increase in bone density at the spine in the calcitonin group was not sustained and a loss of 1.8%/year was observed in the second year. The difference with the placebo group remained significant.
525. Mutants of phiC31 Integrase with Increased Efficiency and Specificity
Authors: Annahita Keravala, Solomon Lee, Eric C. Olivares, Bhaskar Thyagarajan, Alfonso Farruggio, Vanessa E. Gabrovsky, Michele P. Calos
Journal: Molecular Therapy (2006)

The site-specific integrase from bacteriophage phiC31, catalyzes precise, unidirectional recombination between two 30-40 bp sequences, a phage attachment site (attP) and a bacterial attachment site (attB). In mammalian cells, phiC31 integrase can recombine its own sites and can also integrate plasmids with the attB site into native sequences that bear partial identity to attP, referred to as pseudo attP sites. The enzyme recognizes a hierarchy of such sites and, in cell lines, appears to have several hundred potential integration sites, though most integration events occur at a subset of preferred sites. For the purpose of gene therapy, it appears desirable to obtain integration at only one or a small set of safe, well-expressed locations in the genome. In a previous study we demonstrated that by using a genetic screening assay in E. coli, we could create mutant forms of phiC31 integrase with enhanced preference for a pre-existing favored integration site in the human genome. However, this enzyme displayed a low overall integration efficiency. To create phiC31 integrase mutants with enhanced functionality, we devised a screen in mammalian cells to identify mutants with increased recombination efficiency at the attP site. We isolated a collection of such mutants, and combination of several of them led to the identification of an enzyme that mediated the majority of integration events at a single location, at a pre-integrated attP site. This enzyme may be useful for the rapid creation of cell lines with integration at a fixed location. The study also provided proof-of-principle for creation of integrases highly specific for endogenous sequences, a project is underway in the lab. Other mutants from the screen showed an elevated integration frequency at endogenous pseudo attP sites and are being tested in animals as improved gene therapy tools. We have also undertaken the structural characterization of phiC31 integrase. The location of the DNA-binding domain is being investigated by creating deletion mutants and examining them for att site binding with gel mobility shift assays. The increased efficiency and specificity attainable via mutagenesis and protein design will further enhance the utility of phiC31 integrase as a valuable tool in gene therapy. Michele P Calos is a co-founder and consultant for Poetic Genetics, LLC, which has licensed the phiC31 integrase technology.
Visualization of Discrete Microinfarction After Percutaneous Coronary Intervention Associated With Mild Creatine Kinase-MB Elevation
Authors: Mark J. Ricciardi, Edwin Wu, Charles J. Davidson, Kelly M. Choi, Francis J. Klocke, Robert O. Bonow, Robert M. Judd, Raymond J. Kim
Journal: Circulation (2001)

Background —Mild elevations in creatine kinase-MB (CK-MB) are common after successful percutaneous coronary interventions and are associated with future adverse cardiac events. The mechanism for CK-MB release remains unclear. A new contrast-enhanced MRI technique allows direct visualization of myonecrosis. Methods and Results —Fourteen patients without prior infarction underwent cine and contrast-enhanced MRI after successful coronary stenting; 9 patients had procedure-related CK-MB elevation, and 5 did not (negative controls). The mean age of all patients was 61 years, 36% had diabetes, 43% had multivessel coronary artery disease, and all had a normal ejection fraction. Twelve patients (86%) received an intravenous glycoprotein IIb/IIIa inhibitor; none underwent atherectomy, and all had final TIMI 3 flow. Of the 9 patients with CK-MB elevation, 5 had a minor side branch occlusion during stenting, 2 had transient ECG changes, and none developed Q-waves. The median CK-MB was 21 ng/mL (range, 12 to 93 ng/mL), which is 2.3× the upper limit of normal. Contrast-enhanced MRI demonstrated discrete regions of hyperenhancement within the target vessel perfusion territory in all 9 patients. Only one developed a new wall motion abnormality. The median estimated mass of myonecrosis was 2.0 g (range, 0.7 to 12.2 g), or 1.5% of left ventricular mass (range, 0.4% to 6.0%). Hyperenhancement persisted in 5 of the 6 who underwent a repeat MRI at 3 to 12 months. No control patient had hyperenhancement. Conclusions —Contrast-enhanced MRI provides an anatomical correlate to biochemical evidence of procedure-related myocardial injury, despite the lack of ECG changes or wall motion abnormalities. Mild elevation of CK-MB after percutaneous coronary intervention is the result of discrete microinfarction.
Doctors arrested and beaten up in Turkey
Authors: J. Jones
Journal: BMJ (1999)

The Human Rights Foundation of Turkey has protested about the fate of two doctors recently detained and allegedly beaten by police. Both doctors have worked for the Treatment and Rehabilitation Centre run in Izmir by the foundation.

Gynaecologist Dr Zeki Azun was detained in a raid on his private clinic in Izmir on 19 October while he was seeing three …
The Drug Drama
Authors: J. B. Harman
Journal: BMJ (1965)

<h3>Background</h3> Cutaneous lymphomas are a heterogeneous group of lymphomas characterised by T and B clonal lymphoproliferative infiltrates that appear and remain confined to the skin without evidence of involvement of other organs/systems in the six months following diagnosis. Some subtypes of cutaneous T epidermotropic lymphomas respond favourably to topical treatment with steroids. Betamethasone dipropionate is a synthetic high-potency glucocorticoid with anti-inflammatory and immunosuppressive action used as the main topical treatment in the early stages of LNH-T–Mycosis Fungoides, or as an adjuvant treatment in advanced stages of the disease. In the Portuguese pharmaceutical market only a 0.05% (w/w) (0.5 mg/g) cream is available although for this therapeutic indication strengths in a range of 0.025%–0.1% (w/w) are required. This was already an off-label clinical use and a higher concentration was required due to insufficient response to the concentration available. <h3>Purpose</h3> To prepare and characterise a topical 0.1% (w/w) (1 mg/g) betamethasone (dipropionate) cream and evaluate the overall response in cutaneous T-cell lymphomas. <h3>Materials and Methods</h3> Several batches of a compounded W/O emulsion containing betamethasone 0.1% (w/w) (1 mg/g) were prepared and analysed for macroscopic characteristics, pH, rheological properties and microbiological quality (total germs, fungal, yeasts and E. coli). Patients were evaluated monthly and the overall response was recorded (CR-cutaneous lesion totally disappeared; PR-partial remission – objective response &gt;50%&lt;100%; Stabilized disease if cutaneous lesions were similar; No response if cutaneous lesions worsened). <h3>Results</h3> We obtained a white, homogeneous, opaque and odourless cream with a pseudoplastic behaviour. The pH of the formulations at 22 ± 3ºC was 5 (±0.5). Microbiological control for non-sterile products revealed no growth of micro-organisms. By the end of the first month one patient (11.1%) showed partial remission, the others (88.9%) had their cutaneous disease lesions stabilised. <h3>Conclusions </h3> The topical emulsion developed has pH values and rheological characteristics suitable for drug stability and topical skin application. Clinical data is still insufficient for any conclusions. No conflict of interest.
Reporting Mortality Findings in Trials of Rofecoxib for Alzheimer Disease or Cognitive Impairment
Authors: Bruce M. Psaty, Richard A. Kronmal
Journal: JAMA (2008)

Sponsors have a marketing interest to represent their products in the best light. This approach conflicts with scientific standards that require the symmetric and comparable reporting of safety and efficacy data. Selective reporting of the results of clinical trials can misrepresent the risk-benefit profile of drugs. We summarize how the sponsor represented mortality findings associated with rofecoxib in clinical trials of patients with Alzheimer disease or cognitive impairment. We reviewed documents that became available during litigation related to rofecoxib involving Merck & Co, including internal company analyses and information provided by the sponsor to the FDA. We also evaluated information in 2 published articles that reported results of these trials. In one article (reporting results of protocol 091) published in 2004, 11 "non-drug related deaths" were reported (9 deaths among 346 rofecoxib patients and 2 deaths among 346 placebo patients). In another article (reporting results of protocol 078) published in 2005, 39 deaths were reported among patients taking study treatment or within 14 days of the last dose (24 among 725 rofecoxib patients and 15 among 732 placebo patients) and an additional 22 deaths in the off-drug period (17 in rofecoxib patients and 5 in placebo patients). However, these articles did not include analyses or statistical tests of the mortality data, and the 2 articles concluded that regarding safety, rofecoxib is "well tolerated." In contrast, in April 2001, the company's internal intention-to-treat analyses of pooled data from these 2 trials identified a significant increase in total mortality (hazard ratio [HR], 4.43; 95% CI, 1.26-15.53 for protocol 091, and HR, 2.55; 95% CI, 1.17-5.56 for protocol 078), with overall mortality of 34 deaths among 1069 rofecoxib patients and 12 deaths among 1078 placebo patients (HR, 2.99; 95% CI, 1.55-5.77). These mortality analyses were neither provided to the FDA nor made public in a timely fashion. The data submitted by the sponsor to the FDA in a Safety Update Report in July 2001 used on-treatment analysis methods and reported 29 deaths (2.7%) among 1067 rofecoxib patients and 17 deaths (1.6%) among 1075 placebo patients. This on-treatment approach to reporting minimized the appearance of any mortality risk. In December 2001, when the FDA raised safety questions about the submitted safety data, the sponsor did not bring these issues to an institutional review board for review and revealed that there was no data and safety monitoring board for the protocol 078 study. The findings from this case study suggest that additional protections for human research participants, including new approaches for the conduct, oversight, and reporting of industry-sponsored trials, are necessary.