tbuckley/cabot-search huggingface dataset:
Ruptured Uterus after Buccal Oxytocin
Authors: H. O. Nicholson
Journal: BMJ (1964)

CJOUnNc L tion necessary.The one case had taken only small oral doses of ergotamine; the other was receiving subcutaneous dihydroergotamine.This report was referred to in our article' in the British Medical 7ournal four years ago.Our own report was on gangrenous ergotism in a woman of 45 who had taken only 7 tablets, each containing 1 mg.ergotamine tartrate, over three days-not for migraine.Amputation of both legs, the right thumb, and tip of right index finger had to be performed.We believe that migraine confers immunity to possible side-effects from ergotamine, and further that the route of administration is probably of little importance.In some cases side-effects may arise because of abnormal response to accepted therapeutic dosage.The smallest possible dose that will control the symptoms of migraine must be found by gradually increasing the dose with each attack-increasing from 1 mg.by 1 mg.increments, respectively, in subsequent attacks until either a satisfactory dose is thus safely found, or side-effects are too severe.Paraesthesiae, coldness, and pains in the extremities should be reported at once.-We are, etc.,
Sound Footing or Slippery Slope? The Value of Secondary Analyses of Randomized Trials
Authors: Daniel Sargent, Axel Grothey
Journal: Journal of Clinical Oncology (2007)

The accepted standard for the adoption of a new therapy, whether a drug, device, or treatment strategy, is the randomized phase III clinical trial. The justification for basing patient care decisions on such rigorous investigations is clear. These trials have prospectivelyspecifiedhypotheses;limitbiasthroughwell-defined patient selection, random assignment, and blinding (when possible); have clearly defined primary and secondary end points; and have analysis plans that are prespecified. However, the cost, complexity, and time to perform such trials, as well as practical and ethical considerations, are such that not every question can be addressed in a prospective phase III randomized trial. Because datasets from randomized clinical trials contain vast amounts of information, additional hypotheses can be generated, optimally to be explored in subsequent trials. Thus, techniques such as metaanalyses, retrospective analyses, and statistical modeling are increasingly being used to enhance our base of knowledge.
SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints
Authors: Julia Vogt, Kathrin Bengesser, Kathleen BM Claes, Katharina Wimmer, Victor-Felix Mautner, Rick van Minkelen, Eric Legius, Hilde Brems, Meena Upadhyaya, Josef Högel, Conxi Lazaro, Thorsten Rosenbaum, Simone Bammert, Ludwine Messiaen, David N Cooper, Hildegard Kehrer-Sawatzki
Journal: Genome biology (2014)

Abstract Background Genomic disorders are caused by copy number changes that may exhibit recurrent breakpoints processed by nonallelic homologous recombination. However, region-specific disease-associated copy number changes have also been observed which exhibit non-recurrent breakpoints. The mechanisms underlying these non-recurrent copy number changes have not yet been fully elucidated. Results We analyze large NF1 deletions with non-recurrent breakpoints as a model to investigate the full spectrum of causative mechanisms, and observe that they are mediated by various DNA double strand break repair mechanisms, as well as aberrant replication. Further, two of the 17 NF1 deletions with non-recurrent breakpoints, identified in unrelated patients, occur in association with the concomitant insertion of SINE/variable number of tandem repeats/ Alu (SVA) retrotransposons at the deletion breakpoints. The respective breakpoints are refractory to analysis by standard breakpoint-spanning PCRs and are only identified by means of optimized PCR protocols designed to amplify across GC-rich sequences. The SVA elements are integrated within SUZ12P intron 8 in both patients, and were mediated by target-primed reverse transcription of SVA mRNA intermediates derived from retrotranspositionally active source elements. Both SVA insertions occurred during early postzygotic development and are uniquely associated with large deletions of 1 Mb and 867 kb, respectively, at the insertion sites. Conclusions Since active SVA elements are abundant in the human genome and the retrotranspositional activity of many SVA source elements is high, SVA insertion-associated large genomic deletions encompassing many hundreds of kilobases could constitute a novel and as yet under-appreciated mechanism underlying large-scale copy number changes in the human genome.
Mitochondrial ATP-Sensitive Potassium Channels Inhibit Apoptosis Induced by Oxidative Stress in Cardiac Cells
Authors: Masaharu Akao, Andreas Ohler, Brian O’Rourke, Eduardo Marbán
Journal: Circulation Research (2001)

Abstract —Mitochondria can either enhance or suppress cell death. Cytochrome c release from mitochondria and depolarization of the mitochondrial membrane potential (ΔΨ) are crucial events in triggering apoptosis. In contrast, activation of mitochondrial ATP-sensitive potassium (mitoK ATP ) channels prevents lethal ischemic injury in vivo, implicating these channels as key players in the process of ischemic preconditioning. We probed the relationship between mitoK ATP channels and apoptosis in cultured neonatal rat cardiac ventricular myocytes. Incubation with 200 μmol/L hydrogen peroxide induced TUNEL positivity, cytochrome c translocation, caspase-3 activation, poly(ADP-ribose) polymerase cleavage, and dissipation of ΔΨ. Pharmacological opening of mitoK ATP channels by diazoxide (100 μmol/L) preserved mitochondrial integrity and suppressed all markers of apoptosis. Diazoxide prevented ΔΨ depolarization in a concentration-dependent manner (EC 50 ≈40 μmol/L, with saturation by 100 μmol/L), as shown by both flow cytometry and quantitative image analysis of cells stained with fluorescent ΔΨ indicators. These cytoprotective effects of diazoxide were reproduced by pinacidil, another mitoK ATP agonist, and blocked by the mitoK ATP channel antagonist 5-hydroxydecanoate (500 μmol/L). Our findings identify a novel mitochondrial pathway that is protective against apoptosis. The results also pinpoint mitoK ATP channels as logical therapeutic targets in diseases of enhanced apoptosis and oxidative stress.
Bone destruction, upward migration, and medialisation of rheumatoid shoulder: a 15 year follow up study
Authors: J T Lehtinen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To evaluate bone destruction, upward migration, and medialisation of the glenohumeral (GH) joint in a cohort of 74 patients with seropositive and erosive rheumatoid arthritis followed up prospectively. <h3>METHODS</h3> At the 15 year follow up 148 shoulders were radiographed by a standard method. Bone destruction in the GH joint was examined from the radiographs by four methods, of which three measured the migration and one the remodelling of the humeral head. The distances from the greater tuberosity of the humeral head to the coracoid process (medialisation distance (MD)) and to the articular surface of the humeral head (GA) have been previously developed to evaluate the preoperative offsets of the arthritic GH joint. Medial displacement index (MI) and upward migration index (UI) have been recently developed to evaluate the destructive pattern of the rheumatoid GH joint. Destruction of the GH joints was assessed by the Larsen method on a scale of 0 to 5. The relation between the measurements and the grade of destruction of the GH joints was examined. UI was compared with our previous measurements of the subacromial space. <h3>RESULTS</h3> Both the MI and the UI had a negative correlation with the GH joint destruction (Larsen grade), <i>r</i>=−0.49 (95% CI −0.36 to −0.60) and <i>r</i>=−0.58 (95% CI −0.46 to −0.68). The UI correlated significantly with the subacromial space, <i>r</i>=0.90 (95% CI 0.86 to 0.93). The mean MI and UI measurements of the non-affected joints were within the reported normal variation. The mean MD collapsed between Larsen grades 4 (83.0 mm) and 5 (65.5 mm). The morphology of the humeral head began to flatten and erode from the grade 3 onwards and medial head destruction was detected at grade 5. <h3>CONCLUSIONS</h3> Medialisation seems to be preceded by upward migration of the humeral head, indicating rotator cuff damage. Symptomatic Larsen grade 3 shoulders should be intensively followed up by clinical and radiological means. If a total shoulder arthroplasty is considered, an orthopaedic consultation is worthwhile at a sufficiently early stage (Larsen 3 and 4), when soft tissue structures responsible for function are still in proper condition and timing of the operative procedure can be well planned.
UNITY AND DIVERSITY OF SCHIZOPHRENIA: CLINICAL AND LOGICAL ANALYSIS OF THE CONCEPT OF SCHIZOPHRENIA
Authors: HENRI EY
Journal: American Journal of Psychiatry (1959)

1. This clinical and logical analysis of the concept of schizophrenia is drawn from a statistical work on 366 cases studied for an average of 15 years, with a catamnestic period of 5 years at least. 2. As a chronic psychosis, schizophrenia must be separated from acute delusional psychoses. 3. As a chronic delusion tending to dissociation of the ego (with breaking of the communications with others and alteration of the reality) schizophrenia is different from the other forms of chronic delusions (paranoia and paraphrenia). 4. As a delusion, schizophrenia is different from the neuroses. 5. It is only these delimitations that will enable us to define clearly the group of schizophrenias.
Plaque thickness and morphology in psoriasis vulgaris associated with therapeutic response
Authors: T. Rakkhit, J.M. Panko, T.E. Christensen, B. Wong, T. Nelson, J. Papenfuss, C.B. Hansen, K. Callis-Duffin, G.G. Krueger
Journal: British Journal of Dermatology (2009)

Background The Utah Psoriasis Initiative (UPI) is an expanding database that is being used to identify and characterize phenotypic variants of psoriasis and explore genotype–phenotype relationships. We recently reported distinct morphological variants of psoriasis that are characterized by thickness of lesions (induration) in the untreated state. Objectives To explore the clinical relevance of these morphological variants. Methods For these analyses, we used the phenotypic data from 282 additional subjects gathered at enrolment into the UPI and compared their phenotype with that of the original 500 patients reported previously. The analysis was further expanded via a longitudinal follow‐up of 286 subjects from the original 500 case cohort. Results Firstly, the initial findings were confirmed. Expansion of the cohort used for the original observation by about 50% and reanalysis showed that there was no alteration in the proportions of patients expressing thin‐ and thick‐plaque disease phenotypes. Secondly, analysis of the larger cohort showed that this morphological phenotype had clinical relevance: those patients with thin‐plaque disease were more likely to report a complete therapeutic response to topical corticosteroids and phototherapy. In contrast, plaque thickness did not appear to be a factor in response to systemic agents. Conclusions Using a patient's baseline plaque morphology to choose a primary treatment modality may result in earlier disease improvement and reduce the cost of therapy.
MATHEMATICAL MODELING OF TUMOR-INDUCED ANGIOGENESIS
Authors: M.A.J. Chaplain, S.R. McDougall, A.R.A. Anderson
Journal: Annual Review of Biomedical Engineering (2006)

Angiogenesis, the growth of a network of blood vessels, is a crucial component of solid tumor growth, linking the relatively harmless avascular and the potentially fatal vascular growth phases of the tumor. As a process, angiogenesis is a well-orchestrated sequence of events involving endothelial cell migration and proliferation; degradation of tissue; new capillary vessel formation; loop formation (anastomosis) and, crucially, blood flow through the network. Once there is flow associated with the nascent network, subsequent growth evolves both temporally and spatially in response to the combined effects of angiogenic factors, migratory cues via the extracellular matrix, and perfusion-related hemodynamic forces in a manner that may be described as both adaptive and dynamic. In this article, we first present a review of previous theoretical and computational models of angiogenesis and then indicate how recent developments in flow models are providing insight into antiangiogenic and chemotherapeutic drug treatment of solid tumors.
Hedgehog Wnteraction in colorectal cancer
Authors: G R van den Brink
Journal: Gut (2006)

The Hedgehog pathway was recently shown to antagonise constitutive activity of the Wnt pathway that drives proliferation of colorectal cancer cells. Studies in this issue of Gut refine our understanding of the underlying mechanism and provide evidence for such antagonism in colorectal cancers in vivo

The mucosa of the colon is covered by a single layer of epithelial cells that is replaced once every 3–7 days. New cells are produced by a pool of progenitor cells that lie at the base of small mucosal invaginations called crypts. It has been estimated that these progenitor cells generate approximately 10 billion new cells per day in the human colon.1 Homeostasis in such a massive process of regeneration can only be achieved if the behaviour of cells in the system is not regulated at the level of the individual cell (intrinsic). Instead, the fate of individual epithelial cells must be determined by extra cellular (extrinsic) signals that are generated at the population level. It is now becoming clear that these extrinsic signals are provided by morphogens, a class of molecules that has been identified by developmental biologists who studied patterning events during embryogenesis.2 Morphogens are soluble proteins that form long range concentration gradients and act in a dose dependent manner to induce distinct cellular responses on their target cells. In this way, cellular fate is determined by the distance of a target cell from the source of the morphogen. Several morphogens have now been identified as regulators of cell fate in the adult colon.

The Wnt pathway (fig 1) was the first morphogenetic pathway that was implicated in colonic epithelial homeostasis when it was found that adenomatous polyposis coli (APC) acts as an important regulator of Wnt signalling.3 APC had initially been identified as the gene mutated in patients with …
Comparative genomics reveals 104 candidate structured RNAs from bacteria, archaea, and their metagenomes
Authors: Zasha Weinberg, Joy X Wang, Jarrod Bogue, Jingying Yang, Keith Corbino, Ryan H Moy, Ronald R Breaker
Journal: Genome biology (2010)

Structured noncoding RNAs perform many functions that are essential for protein synthesis, RNA processing, and gene regulation. Structured RNAs can be detected by comparative genomics, in which homologous sequences are identified and inspected for mutations that conserve RNA secondary structure.By applying a comparative genomics-based approach to genome and metagenome sequences from bacteria and archaea, we identified 104 candidate structured RNAs and inferred putative functions for many of these. Twelve candidate metabolite-binding RNAs were identified, three of which were validated, including one reported herein that binds the coenzyme S-adenosylmethionine. Newly identified cis-regulatory RNAs are implicated in photosynthesis or nitrogen regulation in cyanobacteria, purine and one-carbon metabolism, stomach infection by Helicobacter, and many other physiological processes. A candidate riboswitch termed crcB is represented in both bacteria and archaea. Another RNA motif may control gene expression from 3'-untranslated regions of mRNAs, which is unusual for bacteria. Many noncoding RNAs that likely act in trans are also revealed, and several of the noncoding RNA candidates are found mostly or exclusively in metagenome DNA sequences.This work greatly expands the variety of highly structured noncoding RNAs known to exist in bacteria and archaea and provides a starting point for biochemical and genetic studies needed to validate their biologic functions. Given the sustained rate of RNA discovery over several similar projects, we expect that far more structured RNAs remain to be discovered from bacterial and archaeal organisms.
Identification of a Novel Pathway That Selectively Modulates Apoptosis of Breast Cancer Cells
Authors: Alexander A. Tinnikov, Kay T. Yeung, Sharmistha Das, Herbert H. Samuels
Journal: Cancer Research (2009)

Abstract Expression of the nuclear receptor interacting factor 3 (NRIF3) coregulator in a wide variety of breast cancer cells selectively leads to rapid caspase-2–dependent apoptotic cell death. A novel death domain (DD1) was mapped to a 30–amino acid region of NRIF3. Because the cytotoxicity of NRIF3 and DD1 seems to be cell type–specific, these studies suggest that breast cancer cells contain a novel “death switch” that can be specifically modulated by NRIF3 or DD1. Using an MCF-7 cell cDNA library in a yeast two-hybrid screen, we cloned a factor that mediates apoptosis by DD1 and refer to this factor as DD1-interacting factor-1 (DIF-1). DIF-1 is a transcriptional repressor that mediates its effect through SirT1, and this repression is attenuated by the binding of NRIF3/DD1. DIF-1 expression rescues breast cancer cells from NRIF3/DD1-induced apoptosis. Small interfering RNA (siRNA) knockdown of DIF-1 selectively leads to apoptosis of breast cancer cells, further suggesting that DIF-1 plays a key role in NRIF3/DD1-mediated apoptosis. A protein kinase A inhibitor (H89) also elicits apoptosis of breast cancer cells but not of the other cell types examined, and DIF-1 also protects these cells from H89-mediated apoptosis. In addition, H89 incubation results in a rapid increase in NRIF3 levels and siRNA knockdown of NRIF3 protects breast cancer cells from H89-mediated apoptosis. Our results indicate that DIF-1 plays a key role in breast cancer cell survival and further characterizing this pathway may provide important insights into developing novel therapies to selectively target breast cancer cells for apoptosis. [Cancer Res 2009;69(4):1375–82]
Initial empiric broad-spectrum antibiotics has no impact on mortality outcome but is associated with increased acquisition of multi-drug resistant bacteria amongst Intensive Care Unit (ICU) patients
Authors: Catherine W.M. Ong, Anupama Vasudevan, Chian Bang Chiang, Chee Kiat Tan, Amartya Mukhopadhyay, Paul Ananth Tambyah
Journal: Journal of Infection (2009)
Neonate With Choking
Authors: Erin E. Shaughnessy, Alexander Towbin, John Prosser
Journal: JAMA Pediatrics (2015)

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 Pediatrics 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 Pediatrics journal
Edward Jenner: the Man and His Work
Authors: E. A. Underwood
Journal: BMJ (1949)

The two-hundredth anniversary of the birth of Edward Jenner, "the discoverer of vaccination," was celebrated on Tuesday, May 17, and the time is opportune for a brief review of Jenner's life and the beginning of the new idea which he inaugurated, and which he was fortunate in seeing widely established in his lifetime.No man has suffered more from the excessive eulogy of well-meaning friends and later admirers, or from the invective of those who for some reason or other did not subscribe to his views.Early Life Edward Jenner was the son of the Rev. Stephen Jenner, rector of Rockhampton and vicar of Berkeley, in Gloucestershire.Born on May 17, 1749, he was educated at first at Wotton-under-Edge under a Mr. Clissold, and then went as a pupil of the Rev
Aging and Cancer-Related Loss of Insulin-like Growth Factor 2 Imprinting in the Mouse and Human Prostate
Authors: Vivian X. Fu, Joseph R. Dobosy, Joshua A. Desotelle, Nima Almassi, Jonathan A. Ewald, Rajini Srinivasan, Mark Berres, John Svaren, Richard Weindruch, David F. Jarrard
Journal: Cancer Research (2008)

Abstract Loss of imprinting (LOI) is an epigenetic alteration involving loss of parental origin-specific expression at normally imprinted genes. A LOI for Igf2, a paracrine growth factor, is important in cancer progression. Epigenetic modifications may be altered by environmental factors. However, is not known whether changes in imprinting occur with aging in prostate and other tissues susceptible to cancer development. We found a LOI for Igf2 occurs specifically in the mouse prostate associated with increased Igf2 expression during aging. In older animals, expression of the chromatin insulator protein CTCF and its binding to the Igf2-H19 imprint control region was reduced. Forced down-regulation of CTCF leads to Igf2 LOI. We further show that Igf2 LOI occurs with aging in histologically normal human prostate tissues and that this epigenetic alteration was more extensive in men with associated cancer. This finding may contribute to a postulated field of cancer susceptibility that occurs with aging. Moreover, Igf2 LOI may serve as a marker for the presence of prostate cancer. [Cancer Res 2008;68(16):6797–802]