tbuckley/cabot-search huggingface dataset:
Determining if Telomeres Matter in Colon Cancer Initiation or Progression
Authors: J. W. Shay
Journal: JNCI Journal of the National Cancer Institute (2013)

The nucleus of each human cell contains 46 linear chromosomes (92 ends) that are capped by thousands of repetitive TTAGGG DNA sequences (similar to the plastic tips on shoelaces). These ends, called “telomeres” have complex roles in aging and cancer and have proven to be intricately involved in such pivotal processes as the protection of genetic material, the completion of chromosome replication, the regulation of cellular aging due to progressively shortening telomeres throughout life, the initial protection against unlimited cellular growth, and, in combination with other alterations, the promotion of cancer progression. A collection of six proteins that either bind or associate with telomeres (the shelterin complex) begin to resolve a central question of how cells distinguish telomere ends from typical genomic DNA double-strand breaks (1). The consequences of telomere dysfunction are becoming more apparent by examining a growing list of human genetic diseases called telomeropathies. In certain inherited and familial cases of idiopathic pulmonary fibrosis, dyskeratosis congenita, and sporadic bone marrow failure (aplastic anemia), inheritance of short telomeres due to mutations in genes involved in the ribonucleoprotein telomerase holoenzyme lead to premature aging phenotypes (2). Telomerase is the cellular reverse transcriptase that can add TTAGGG repeats onto the telomeres and is active during early human development (3) but is silent in most adult tissues except proliferating stem cells, unless it is upregulated as part of cancer progression (4).
Current Perspective on the Pathogenesis of Graves’ Disease and Ophthalmopathy
Authors: Bellur S. Prabhakar, Rebecca S. Bahn, Terry J. Smith
Journal: Endocrine Reviews (2003)

Graves' disease (GD) is a very common autoimmune disorder of the thyroid in which stimulatory antibodies bind to the thyrotropin receptor and activate glandular function, resulting in hyperthyroidism. In addition, some patients with GD develop localized manifestations including ophthalmopathy (GO) and dermopathy. Since the cloning of the receptor cDNA, significant progress has been made in understanding the structure-function relationship of the receptor, which has been discussed in a number of earlier reviews. In this paper, we have focused our discussion on studies related to the molecular mechanisms of the disease pathogenesis and the development of animal models for GD. It has become apparent that multiple factors contribute to the etiology of GD, including host genetic as well as environmental factors. Studies in experimental animals indicate that GD is a slowly progressing disease that involves activation and recruitment of thyrotropin receptor-specific T and B cells. This activation eventually results in the production of stimulatory antibodies that can cause hyperthyroidism. Similarly, significant new insights have been gained in our understanding of GO that occurs in a subset of patients with GD. As in GD, both environmental and genetic factors play important roles in the development of GO. Although a number of putative ocular autoantigens have been identified, their role in the pathogenesis of GO awaits confirmation. Extensive analyses of orbital tissues obtained from patients with GO have provided a clearer understanding of the roles of T and B cells, cytokines and chemokines, and various ocular tissues including ocular muscles and fibroblasts. Equally impressive is the progress made in understanding why connective tissues of the orbit and the skin in GO are singled out for activation and undergo extensive remodeling. Results to date indicate that fibroblasts can act as sentinel cells and initiate lymphocyte recruitment and tissue remodeling. Moreover, these fibroblasts can be readily activated by Ig in the sera of patients with GD, suggesting a central role for them in the pathogenesis. Collectively, recent studies have led to a better understanding of the pathogenesis of GD and GO and have opened up potential new avenues for developing novel treatments for GD and GO.
Delayed Onset of Signs in Extradural Haemorrhage
Authors: P. R. R. Clarke, D. C. Jenkins
Journal: BMJ (1955)

given in the evening.Reduction in the maintenance dosage of ecolid was possible and side-effects were fewer.During the period of observation, tolerance to ecolid has not developed, and in some cases reduction of dosage has been possible.The response was good in eight cases and fair in one, the drug being stopped in the remaining three owing to severity of side-actions.These results are summarized in the Table.Summary of Results of Treatment of 12 Patients with Severe Hypertension.Meanz Blood Pressures when Recumi1bent ar-e Recorded.Patients 7-12 Recei.edAlso 2 tIug.Reserpine bY Mouth at Night Sex Tpe of B.P. B.P.
Nicaragua's abortion ban criminalises doctors and endangers lives of women, says report
Authors: A. Cole
Journal: BMJ (2009)

Doctors in Nicaragua face imprisonment and loss of their licence to practise if they provide pregnant women with therapeutic abortions or with treatment for an unrelated condition that harms their unborn baby, a new report from Amnesty International says.

The report says that the lives and health of women and girls are being placed at serious risk after the country imposed a complete ban on all abortions in the country a year ago.

The new law, which was opposed by 21 Nicaraguan medical associations, means that women face imprisonment for seeking an abortion even if their pregnancy puts their life …
Do Alternate Modes for Transmission of Human Immunodeficiency Virus Exist?
Authors: Alan R. Lifson
Journal: JAMA (1988)

Transmission of human immunodeficiency virus (HIV) is known to occur perinatally, through sexual contact, and after exposure to infected blood or blood products. The possibility that breast milk may transmit HIV continues to be evaluated. There is no epidemiologic evidence that contact with saliva, tears, or urine has resulted in HIV infection. However, because HIV has (in some cases rarely) been isolated from these body fluids, guidelines have been developed to reduce more extensive exposures to such secretions. Laboratory and epidemiologic data strongly indicate that HIV is not transmitted through immune globulin preparations, the hepatitis B vaccine, or contact with insects. Increasing evidence from many studies also indicates that HIV is not transmitted through casual contact. All individuals need to be aware of how HIV is and is not transmitted, to reduce high-risk behaviors and to avoid unnecessary fears and actions.
Hepatitis B e antigen in sera from individuals infected with hepatitis B virus of genotype G
Authors: Hideaki Kato, Etsuro Orito, Robert G. Gish, Natalie Bzowej, Margaret Newsom, Fuminaka Sugauchi, Seiji Suzuki, Ryuzo Ueda, Yuzo Miyakawa, Masashi Mizokami
Journal: Hepatology (2002)

Hepatitis B virus (HBV) genotype G (HBV/G) was detected in sera from four individuals by polymerase chain reaction with hemi-nested primers deduced from an insertion of 36 nt in the core gene that is specific for this genotype. Despite two stop codons in the precore region characteristic of HBV/G, all patients were positive for hepatitis B e antigen (HBeAg) in serum. When 10 HBV clones were propagated from one patient, and sequenced within precore region and a section of the core gene, 6 clones were HBV/G while 2 were genotype A (HBV/A); a recombination between HBV/G and HBV/A occurred in the remaining 2 clones. Mixed infection of HBV/G and HBV/A, as well as the recombination, was demonstrated in the sequence of preS1 and preS2 regions also. Coinfection with HBV/G and HBV/A was demonstrated in the other three patients, and their recombination in two patients. Ten HBV clones were propagated from one patient at two time points separated by 1 year. Clones of HBV/A, HBV/G and their recombination were found in 9 : 1 : 0 when the patient was positive for HBeAg, while the proportion shifted to 0 : 8 : 2 after the patient seroconverted to anti-HBe. In conclusion, HBV/G is frequently found as a coinfection with HBV/A. This coinfection would explain the presence of HBeAg in individuals infected with HBV/G. Along with seroconversion to anti-HBe, HBV/G would be selected accompanied by the recombination with HBV/A. Further studies should be performed to confirm these findings.
Salivary duct calculi presenting as trismus in a child.
Authors: K N Bullock
Journal: BMJ (1980)

Details offive patients on home parenteral nutrition for intestinalfailure Time at Disease and Time on home on Weight at Weight at Case Age Sex nutritional parenteral parenteral start of end of No (years) problem nutrition nutrition treatment treatment (months) (months) (kg) (kg) 1 18 F Polyarteritis 5.-3 28 39 nodosa.Mesenteric vascular occlusion.Short-bowel syndrome 2 21 M Intestinal 13* 9* 45 56 motility disorder.Small and large bowel resection.Short-bowel syndrome 3 36 M Crohn's disease, 10 3 25 47 multiple entero- cutaneous fistulae 4 49 M Mesenteric 5 11 44 52-5 ischaemia, intestinal fistula, short- bowel syndrome 5 34 M Crohn's disease, 5 11 45 57 multiple small bowel resection, short-bowel syndrome
Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis
Authors: Sandra Reynoso-Paz, Patrick S.C. Leung, Judy Van de Water, Atsushi Tanaka, Santiago Munoz, Nathan Bass, Keith Lindor, Paul J. Donald, Ross L. Coppel, Aftab A. Ansari, Eric M. Gershwin
Journal: Hepatology (2000)

Primary biliary cirrhosis (PBC) is often considered to be a dry gland disease caused by frequent involvement of salivary and lacrimal glands. Although high titers of antimitochondrial autoantibodies (AMA) have long been recognized in PBC, little is known about the presence of mitochondrial autoantigens in mucosal compartments such as saliva. We investIgAted saliva and sera in PBC patients and controls for the presence of AMA and mitochondrial antigens. In PBC saliva, AMA were detected in 45 of 49 (92%), with specificity directed against pyruvate dehydrogenase complex (PDC-E2) alone in 22 of 49 (45%), against PDC-E2 and branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 4 of 49 (8%), to PDC-E2 and 2-oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 9 of 49 (18%), and to the 3 antigens together in 10 of 49 (20%). Isotyping of the saliva AMA showed that 80% of the patients had immunoglobulin A (IgA) against PDC-E2, 18% had IgM-specific PDC-E2, and 35% had IgG specific PDC-E2. Similar to serum and bile anti-PDC-E2 IgA antibodies, the saliva autoantibodies localized their reactivity to the inner lipoyl domain of PDC-E2. Furthermore, saliva from patients with PBC but not controls inhibited pyruvate dehydrogenase enzyme activity in vitro . In addition, and of particular interest, we detected a molecule with a molecular weight corresponding to PDC-E2 (74 kd) in PBC but not control saliva. These findings make several important points: first, there appears to be localized mucosal immunity in the secretory system of PBC; second, AMA are readily detected in PBC saliva; and third, PDC-E2 may be present in the saliva of PBC.
Augmented cellular trafficking and endosomal escape of porous silicon nanoparticles via zwitterionic bilayer polymer surface engineering
Authors: Mohammad-Ali Shahbazi, Patrick V. Almeida, Ermei M. Mäkilä, Martti H. Kaasalainen, Jarno J. Salonen, Jouni T. Hirvonen, Hélder A. Santos
Journal: Biomaterials (2014)
Fatal vascular occlusion in juvenile dermatomyositis
Authors: T TAKEDA, A FUJISAKU, S JODO, T KOIKE, A ISHIZU
Journal: Annals of the Rheumatic Diseases (1998)

<h3>BACKGROUND AND PURPOSE:</h3> Endoluminal reconstruction with flow diverting devices represents a novel constructive technique for the treatment of cerebral aneurysms. We present the results of the first prospective multicenter trial of a flow-diverting construct for the treatment of intracranial aneurysms. <h3>MATERIALS AND METHODS:</h3> Patients with unruptured aneurysms that were wide-necked (&gt;4 mm), had unfavorable dome/neck ratios (&lt;1.5), or had failed previous therapy were enrolled in the PITA trial between January and May 2007 at 4 (3 European and 1 South American) centers. Aneurysms were treated with the PED with or without adjunctive coil embolization. All patients underwent clinical evaluation at 30 and 180 days and conventional angiography 180 days after treatment. Angiographic results were adjudicated by an experienced neuroradiologist at a nonparticipating site. <h3>RESULTS:</h3> Thirty-one patients with 31 intracranial aneurysms (6 men; 42–76 years of age; average age, 54.6 years) were treated during the study period. Twenty-eight aneurysms arose from the ICA (5 cavernous, 15 parophthalmic, 4 superior hypophyseal, and 4 posterior communicating segments), 1 from the MCA, 1 from the vertebral artery, and 1 from the vertebrobasilar junction. Mean aneurysm size was 11.5 mm, and mean neck size was 5.8 mm. Twelve (38.7%) aneurysms had failed (or recurred after) a previous endovascular treatment. PED placement was technically successful in 30 of 31 patients (96.8%). Most aneurysms were treated with either 1 (<i>n</i> = 18) or 2 (<i>n</i> = 11) PEDs. Fifteen aneurysms (48.4%) were treated with a PED alone, while 16 were treated with both PED and embolization coils. Two patients experienced major periprocedural stroke. Follow-up angiography demonstrated complete aneurysm occlusion in 28 (93.3%) of the 30 patients who underwent angiographic follow-up. No significant in-construct stenosis (≥50%) was identified at follow-up angiography. <h3>CONCLUSIONS:</h3> Intracranial aneurysm treatment with the PED is technically feasible and can be achieved with a safety profile analogous to that reported for stent-supported coil embolization. PED treatment elicited a very high rate (93%) of complete angiographic occlusion at 6 months in a population of the most challenging anatomic subtypes of cerebral aneurysms.
The Maudsley Lecture on the Prevention of Insanity
Authors: G. M. Robertson
Journal: BMJ (1926)

PROFESSOR ROBERTSON divided hiis subject inito two parts: first, the influences which go to the causation of inisanity; secondly, observations on the theories and methods of pre- vention, particularly of general paraly sis of the insane.The statistics he used were taken fi-om the twelnty-fir st annual report of the Commission in Luniacy of the State of New York for the year 1908-09.C'onditions and Influences Affecting the Occurreence of Insanity.From these statistics it appeared that insanitv unider the ago of 15 was quite negligible and if included in statistics of insanity had a most disturbing effect, as this period of life comprised nearly a third of the population.A high birth rate and a low infantile mortality would increase the population at this period, and the effect of this proportionate increase would be to reduce the apparent amount of insanity in the total population, without any real diminution of insanity.A fair number of admissions occurred between 15 and 19, and a larger number between 20 and 24.The amount continued very high up to 40 years of age, after which it fell, so that it appeared that the early years of life were the most liable to insanitv, and with increasing years a mental breakdown became every year moro remote.But these statistics did not represent the rate of incidence of the liability to insanity-that is say, the froquency with wlhich insanity occurred in propor- tion to the niumber living.The large niumiiber of admissions recorded between 20 and 40 was mainly due to the large number of persons living in early life, and the small number of admissions at 75resulted from the small number alive in old age.Statistics of incidence showed that insanity tended to develop betweeni 15 and 19, but became nmuch more pronounced between 20 and 24.This was followed bv a steady rise vear after year till the age .50 was reached.There was theni a shoit period of decline, after whicih there was an extremely rapid rise in old age.there was a general tendency for insanity to become more frequent as one grew older.To emphasize the differenco between the number of admissions at the various age .periodsand the rate of incidence of insanity at periods Professor Robertson brought the two charts together.for the purpose of comparison. 151 94 3 9 33 44 43 34 59 04 33Fie.1.-Graph of total number of first adimissions (5,222) compared witlh rate of incidence. of insanity per 100,000 of the populatious at quinquennial age periods (ratio 3 to 1).Incidence of Insanity among Males and Females.As regards' sex, insanity occurred among males at a pro- portionately higher rate than among females.This un- expected result was mainly due to the greater number of admissions from general paralysis and alcoholic insanity.
Mobile phones are not lightning strike risk: Injury from lightning strike while using mobile phone
Authors: Chris W Althaus
Journal: BMJ (2006)

EDITOR—The claim in the letter by Esprit et al, that mobile phones are a risk when used in a storm, is misleading.1 Although some people speculate that mobile phones pose a risk when used outdoors because lightning is attracted to metal, mobile phone handsets generally contain insignificant amounts of metal.

Following worldwide media interest in the letter, the US …
Abstract 1740: Risk of Proarrhythmia Following Alcohol Septal Ablation in Patients with Hypertrophic Obstructive Cardiomyopathy
Authors: Saumya Das, Igor Palacios, Gus J Vlahakes, Michael H Picard, Danita Y Sanborn, Patricia A Lowry, Jeremy N Ruskin, Michael A Fifer, Theofanie Mela
Journal: Circulation (2007)

Background: Alcohol septal ablation (ASA) is a promising treatment option for patients with hypertrophic obstructive cardiomyopathy (HOCM), but the creation of myocardial infarct during the procedure has raised concern about the proarrhythmic risk of ASA. We analyzed the incidence of clinically significant ventricular tachycardia (VT) and sudden cardiac death (SCD) following ASA at our center. Methods: A total of 97 ASAs in 88 patients were performed between 1998 and 2007 at MGH. 34 of these patients had an implantable cardiac defibrillator (ICD) or pacemaker (PPM) implanted prior to or immediately following ASA. 8 of 34 patients had prior ICD implants for either secondary (n=4) or primary (n=4) prevention for SCD. 8 patients had prior PPMs. 3 patients had implantation of ICD post-ASA and 15 patients had PPM implanted following ASA due to atrioventricular block (AVB). Clinical records as well as device data were analyzed to determine incidence of VT or SCD following ASA. Results: There were no deaths attributable to SCD in our cohort of 88 patients (mean follow-up 35 +/− 21 months, range 4 to 70 months). 1 patient with a previous ICD for primary prevention had VT storm 6 days following ASA. 1 patient who had a cardiac arrest 11 days following the ASA (thought to be a bradycardic arrest, since he had intermittent high grade AVB post-ASA) received an ICD. Neither of these patients had subsequent detections or therapies for VT. 1 patient was upgraded to an ICD following ASA due to NSVT, and 2 patients had ICD implants for NSVT or high risk of SCD. The former had subsequent detection of NSVT 24 months after implant, and therapy for VT 3 years later. 2 patients had upgrades of their PPM to an ICD &gt; 12 months after ASA (for positive electrophysiology studies at other centers), but had no detection or therapies during the follow-up period. No other patients had therapies for tachyrrhythmias. Conclusion: In our experience of 97 procedures, we observed 1 episode of VT storm in the first week following ASA, 1 cardiac arrest, likely bradycardic, in the first 2 weeks after ASA, and only 1 patient with clinically significant VT years after ASA. Our data suggest that close follow-up is warranted in the 2 weeks after ASA, but that ASA does not seem to have a long-term proarrhythmic effect in patients with HOCM.
Serum Sickness and Recurrent Angioedema After Bee Sting
Authors: Richard K. Sheehan
Journal: JAMA (1965)

LITERATURE on insect sensitivity reactions makes ample mention of hives, angioedema (single episodes), and anaphylactoid and even fatal episodes as consequences of insect stings. Recently, a rather atypical reaction was noted following a bee sting. Because of the bizarre nature of the clinical sequences, it was thought deserving of report.  Report of a Case  A 5-year-old boy was stung by a bee in the left temporal area on Sept 15, 1963. Because of the marked local reaction in the sting area, the child was given emergency treatment with diphenhydramine (Benadryl) hydrochloride, 50 mg intravenously, and triamcinolone (Kenacort), 4 mg orally four times daily, by the family physician. Over the first four days there was gradual improvement. However on the fifth day following the incident marked swelling had again recurred in the sting area, with progression to the left temporofacial area. In spite of repeated medication the child had seven such
Insulin Glulisine May Cause a Disease Resembling Insulin Autoimmune Syndrome: Case Report
Authors: Maki Kawasaki, Yoichi Oikawa, Takeshi Katsuki, Yusuke Kabeya, Masuomi Tomita, Mari Okisugi, Akira Shimada
Journal: Diabetes Care (2013)

Insulin autoimmune syndrome (IAS) is a rare cause of spontaneous hypoglycemia with severe hyperinsulinemia characterized by high titers of insulin antibodies (IAs) without prior insulin injections (1). Whereas IAS is usually caused by drugs containing sulfhydryl compounds or α-lipoic acid (2), we report a disease resembling IAS, possibly induced by insulin glulisine.

A 71-year-old man was diagnosed with type 2 diabetes at 62 years of age in 2003. While he was treated with glimepiride from 2009, his glycemic control remained poor. In October 2010, glimepiride was discontinued and four daily insulin injections, three injections of glulisine and one injection of glargine, were initiated. From around February 2011, he repeatedly suffered nocturnal hypoglycemia along with daytime hyperglycemia. Although glargine was discontinued in July 2011, nocturnal hypoglycemia continued to occur. Therefore, he was admitted to our hospital in May 2012.

When three daily glulisine injections (0.52 units/kg/day) were continued …