tbuckley/cabot-search huggingface dataset:
Tachycardia Preconditions Infarct Size in Dogs
Authors: Raúl J. Domenech, Pilar Macho, Diego Vélez, Gina Sánchez, Xueliang Liu, Naranjan Dhalla
Journal: Circulation (1998)

Background —Myocardial ischemic preconditioning is a well-known phenomenon, however there is scant information in regard to nonischemic preconditioning. Methods and Results —We studied in anesthetized dogs the preconditioning effect of tachycardia and the mediation of adenosine and protein kinase C in this process. In a control group the anterior descending coronary artery was occluded for 60 minutes and reperfused for 270 minutes. Heart rate was kept constant at 120±5 cycles/min and aortic pressure changes were damped. The infarct size (necrotic volume/risk region volume×100) was 15.8±1.5%. In another group of dogs a similar protocol was followed, but five periods of tachycardia (213±12 cycles/min), 5 minutes in duration each, with 5 minutes of intervening periods at control heart rate, were induced previous to the coronary occlusion. The infarct size was reduced by 46% ( P &lt;.001) with respect to the nonpreconditioned group. This effect was not due to changes in collateral flow nor risk region size. During tachycardia, myocardial interstitial adenosine increased about twofold ( P &lt;.05); no metabolic, hemodynamic, or ECG evidences of ischemia were observed and the transmural vasodilatory reserve was preserved. The blockade of adenosine receptors with 8 phenyltheophylline, before or after the preconditioning tachycardia, reverted its protecting effect but it did not modify infarct size in nonpreconditioned dogs. No changes in cytosolic or particulate protein kinase C activity or translocation of α-, β-, ε-, and ζ- protein kinase C isozyme by effect of tachycardia or ischemia were observed between preconditioned and nonpreconditioned dogs. Conclusions —Tachycardia, in the absence of ischemia, mimics the preconditioning effect of ischemia in the dog. This effect is mediated by adenosine but not by changes in protein kinase C activity or its translocation.
The role of apoptosis in autoimmune thyroid disorders and thyroid cancer
Authors: J.-D. Lin
Journal: BMJ (2001)

Apoptosis, or programmed cell death, is an active process of self destruction that requires the activation of a genetic programme that may lead to changes in cell morphology, DNA fragmentation, and protein cross linking.1 Apoptosis can be triggered in several ways and involves many cellular functions.2 The mechanism provides protection from the possible consequences of uncontrolled cell proliferation, which could lead to neoplasia. Cell death is a factor in the pathogenesis of several diseases, including autoimmune disorders, cancer, AIDS, and neurodegenerative diseases. Regulation of apoptosis in cells undergoing proliferation may be the key to reversing the natural progression of these disorders.3 Apoptosis involves the sequential activation of a series of caspases, which are proteolytic enzymes that degrade a number of death substrates. Caspase is activated by two pathways—the mitochondrial pathway and the death receptor pathway—and thereby may trigger nuclear enzymes to degrade chromosomal DNA and alter mitochondrial function. Specific pathways and non-specific signals (such as cytotoxic drugs and radiation) may activate caspase. The most common of these pathways involves death receptors that have structures belonging to the tumour necrosis factor (TNF) receptor superfamily of proteins. Interaction of tumour necrosis factor with this receptor can induce cell death by the activation of various kinase enzymes that act as secondary messengers within the cell.4 Another member of this family, Fas antigen, and its ligand (FasL), are molecules used by immune effector cells to kill targets.5

#### Summary points

Thyroid stimulating hormone (TSH) inhibits Fas expression

Antibodies to TSH receptors inhibit Fas mediated apoptosis

Soluble Fas increases in untreated Graves' disease

Interleukin 1β and TNF-α induce the production of soluble Fas

Fas, DR4, and DR5 are expressed in thyroid carcinoma cell lines

Recombinant TRAIL (TNF related, apoptosis induced ligand) induced apoptosis occurs in 10 thyroid carcinoma cell lines

FasL is strongly …
Serum alkaline phosphatase.
Authors: M M Karl
Journal: BMJ (1968)

The alkaline phosphatases constitute a large group of enzymes of low specificity that are involved in the hydrolysis of phosphate monoesters at a pH of about 9. They also play important roles in the transport of sugar and phosphate in the intestinal mucosa, kidney tubule, placenta, and bones. At the cellular level, they demonstrate activity against a wide variety of substrates but appear to be metabolically inert in the serum. Tissues that demonstrate the highest alkaline phosphatase activity include osteoblasts, bile canaliculi, intestinal mucosa, proximal convoluted tubules, and placenta. Alkaline phosphatase is present in serum, urine, feces, lymph, sweat, and breast milk. Large amounts are present in bile but whether the biliary tract represents the major mode of excretion still remains a matter of dispute. The serum alkaline phosphatase may originate then from bone, intestine, placenta, and the hepatobiliary system. Two possible mechanisms have been proposed to explain the elevated
Death, Dying, and the Zealous Phase
Authors: ROBERT P. HUDSON
Journal: Annals of Internal Medicine (1978)

During the past decade an unprecedented public and professional interest has developed around issues involving death and dying. Persons of differing backgrounds and with different objectives are rushing onto this scene in rapidly increasing numbers. Some of these persons have little understanding of the medical complexities of dying and no clinical experience with dying patients. In this essay I attempt to identify a number of ways in which well-intentioned persons engage dying patients or influence public opinion on death and dying, ways that might prove less than salutary for all concerned.
MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice
Authors: Thomas E. Callis, Kumar Pandya, Hee Young Seok, Ru-Hang Tang, Mariko Tatsuguchi, Zhan-Peng Huang, Jian-Fu Chen, Zhongliang Deng, Bronwyn Gunn, Janelle Shumate, Monte S. Willis, Craig H. Selzman, Da-Zhi Wang
Journal: Journal of Clinical Investigation (2009)

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have gained status as important regulators of gene expression. Here, we investigated the function and molecular mechanisms of the miR-208 family of miRNAs in adult mouse heart physiology. We found that miR-208a, which is encoded within an intron of alpha-cardiac muscle myosin heavy chain gene (Myh6), was actually a member of a miRNA family that also included miR-208b, which was determined to be encoded within an intron of beta-cardiac muscle myosin heavy chain gene (Myh7). These miRNAs were differentially expressed in the mouse heart, paralleling the expression of their host genes. Transgenic overexpression of miR-208a in the heart was sufficient to induce hypertrophic growth in mice, which resulted in pronounced repression of the miR-208 regulatory targets thyroid hormone-associated protein 1 and myostatin, 2 negative regulators of muscle growth and hypertrophy. Studies of the miR-208a Tg mice indicated that miR-208a expression was sufficient to induce arrhythmias. Furthermore, analysis of mice lacking miR-208a indicated that miR-208a was required for proper cardiac conduction and expression of the cardiac transcription factors homeodomain-only protein and GATA4 and the gap junction protein connexin 40. Together, our studies uncover what we believe are novel miRNA-dependent mechanisms that modulate cardiac hypertrophy and electrical conduction.
Precut Papillotomy Versus Persistence in Difficult Biliary Cannulation: A Prospective Randomized Trial
Authors: S.-J. Tang, G. B. Haber, P. Kortan, S. Zanati, M. Cirocco, M. Ennis, A. Elfant, D. Scheider, H. Ter, J. Dorais
Journal: Endoscopy (2005)

Background and Study Aims: Failed biliary cannulation occurs in up to 10 % of patients undergoing ERCP. There is some controversy as to the safety and efficacy of using precut techniques to achieve biliary cannulation in difficult cases. To date, no randomized trial has compared the success and complication rates of precut with the rates for persistence when biliary cannulation is difficult. The aim of this study was to compare the success rates and complication rates of precut with the success rates and complication rates of persistence in cases of difficult biliary cannulation. Patients and Methods: Patients without prior sphincterotomy who required biliary cannulation were screened. A "difficult biliary cannulation" was arbitrarily defined as failed cannulation after 12 minutes. These patients were then randomized to continue treatment by needle-knife cut over the roof of the papilla or by persistence with a non-wire-guided, single-lumen papillotome. "Primary" success was defined as deep cannulation within 15 minutes of randomization. Primary and final success rates and complication rates within 30 days after ERCP were compared. Results: Over a 38-month period a total of 642 patients were screened. Patients in whom biliary cannulation was successful within a time period of 12 minutes or less formed the reference group (n = 580). The remainder of the patients were randomly assigned to the "precut" arm (n = 32) or to the "persistence" arm (n = 30). Primary success rates and complication rates were similar in the precut and persistence arms (75 % and 4 % respectively for the precut arm vs. 73 % and 9 % for the persistence arm). The final successful cannulation rate in the entire group of 642 patients was 99.5 %. Conclusions: In experienced hands, precut papillotomy and persistence in cannulation are equally effective in cases of difficult cannulation, with a similar complication rate.
Changes in neural and humoral mechanisms of the heart in sudden death due to myocardial abnormalities
Authors: Vadim N. Shvalev, Anatoli M. Vikhert, Rimvidas A. Stropus, Alexander A. Sosunov, Eugene R. Pavlovich, Raisa A. Kargina-Terentyeva, Nadezhda I. Zhuchkova, Alexander Y.U. Anikin, Konstantin L. Maryan
Journal: Journal of the American College of Cardiology (1986)
The True 'Pseudo'
Authors: Samuel Vaisrub
Journal: JAMA (1981)

What is true? What is false? What is pseudo? The first two questions may be difficult to answer in an individual case, but in general they are understandable. The third calls for a reflective pause. On the face of it, pseudo is synonymous with false. When prefixing the name of a disease, however, it can give rise to two discordant meanings. In 1942 Albright and his associates described a genetic disease that closely resembled hypoparathyroidism but differed from the latter in its additional clinical features—dwarfism, round head, and short metacarpal and metatarsal bones—and in its pathophysiology. The basic defect responsible for the disordered calcium and phosphorus metabolism was not a quantitative or qualitative deficiency of the parathyroid hormone but the unresponsiveness of renal tubules to its action. Albright et al named the disease pseudohypoparathyroidism. And, when these investigators soon discovered a disease that mimicked pseudohypoparathyroidism in its physical features but
TCT-15 Results of the Primary Endpoint of the PLATINUM PLUS Trial: A Prospective, Randomized, Multi-center Trial to Assess the Everolimus-Eluting Coronary Stent System (PROMUS Element) for Coronary Revascularization in a Population of Unrestricted Patients
Authors: Jean Fajadet, Eulogio J. Garcia, David Hildick-Smith, Franz-Josef Neumann, Anna Sonia Petronio, Mark S. Spence, Jochen Wöhrle, Azfar Zaman, Simon Elhadad, Sigmund Silber
Journal: Journal of the American College of Cardiology (2013)
Reassessing an old claim: Natural selection of hemizygotes and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria
Authors: Giorgio Sirugo
Journal: American Journal of Hematology (2013)

In 1995, from work carried out in Kenya and in The Gambia, Ruwende et al. concluded that hemizygous G6PD-deficient male and heterozygous G6PD-deficient female children in Africa were similarly protected from severe malaria and were selectively advantaged in a malarial environment 1. The recent publication of a detailed map of G6PD deficiency 2, again citing the Ruwende et al. paper in the context of studies of this genetic disorder, has prompted the question whether the data reported by Ruwende et al. can be considered accurate or not. The analysis carried out by Ruwende et al. was not statistically significant from Kenyan data alone, but was based on pooled data from Kenya and The Gambia: however, as detailed above, the latter data were invalid. Regrettably, the incongruences in the Ruwende et al. paper have never been thoroughly and systematically questioned, consequently the paper keeps being widely quoted, having reached a total of over 340 entries in Google Scholar (including the one by Guindo et al. 10) with a potential misleading effect on studies of G6PD and malaria. It is at this point important to recognize that the Ruwende et al. work was based on largely incorrect data, which mandates a complete re-assessment of the conclusions reached at the time of its publication. Giorgio Sirugo Ospedale San Pietro Fatebenefratelli and Tor VergataUniversity School of Medicine, Rome, Italy
Abstract 638: PBF overexpression causes increased p53 ubiquitination and degradation via MDM2.
Authors: Gavin Ryan, Robert Seed, Martin Read, Jim Fong, Andrew Turnell, Vicki Smith, Jayne Franklyn, Christopher McCabe, Kristien Boelaert
Journal: Cancer Research (2013)

Abstract The pituitary tumor-transforming gene-binding factor (PBF) is a relatively uncharacterised proto-oncogene, which is overexpressed in thyroid tumours. PBF elicits tumor growth in nude mice, whilst thyroid targeted transgenic overexpression in the PBF-Tg mouse induces hyperplasia and macrofollicular lesions, accompanied by induction of the E2 ubiquitin ligase Rad6. Our previous unpublished data showed that PBF binds to p53, and reduces stimulation of downstream target genes by competitive binding. Further, half-life studies of p53 showed reduced p53 stability when PBF was overexpressed in K1 and TPC-1 thyroid papillary cancer cell lines, and ubiquitination assays confirmed this was due to increased ubiquitination and subsequent degradation by the proteasome. Now, GST pull-down assays demonstrate direct binding between PBF and MDM2, the principal negative regulator of p53. The competitive inhibitor of p53-MDM2 binding, Nutlin-3, revealed that the increased degradation of p53 observed when PBF was overexpressed was mediated by MDM2. No change in p53-MDM2 binding stringency was detected when PBF expression was ameliorated by siRNA treatment, and MDM2 subcellular localisation was unchanged by PBF overexpression. However, co-immunoprecipitation assays revealed that PBF specifically interacts with Rad6, which has previously been shown to regulate p53 ubiquitination. Further, PBF-Tg mice demonstrated significantly induced genetic instability at 6 weeks of age, as determined by FISSR-PCR. Thus we propose that aberrantly expressed PBF functionally inactivates p53 via a complex interplay between Rad6 and MDM2, thus promoting genetic instability and tumorigenesis. Our studies, carried out in a panel of thyroid and colorectal cells lines, suggest this may be pertinent not only to thyroid cancer, but to colorectal and other tumour types. Citation Format: Gavin Ryan, Robert Seed, Martin Read, Jim Fong, Andrew Turnell, Vicki Smith, Jayne Franklyn, Christopher McCabe, Kristien Boelaert. PBF overexpression causes increased p53 ubiquitination and degradation via MDM2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 638. doi:10.1158/1538-7445.AM2013-638
Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases
Authors: Nathalie Ganne-Carrié, Marianne Ziol, Victor de Ledinghen, Catherine Douvin, Patrick Marcellin, Laurent Castera, Daniel Dhumeaux, Jean-Claude Trinchet, Michel Beaugrand
Journal: Hepatology (2006)

A proper diagnosis of cirrhosis is essential for the management of patients with chronic liver diseases. We assessed the accuracy of liver stiffness measurement by Fibroscan for the diagnosis of cirrhosis in 1,257 patients with chronic liver diseases of various causes enrolled in a prospective multicenter study as well as clarified causes of discrepancies between liver histology and Fibroscan. One hundred thirty-two patients had unsuitable biopsy specimens, and 118 had unreliable liver stiffness measurements. Because 232 patients overlapped with a previous study, analysis was performed in the 775 new patients then derived in the whole population (1,007; 165 cirrhosis). Diagnostic accuracy was assessed by receiver operator curve (ROC) analysis. Liver samples were re-analyzed in case of discrepancies. The area under the ROC (AUROC) was 0.95 (95% CI, 0.93-0.96) for the diagnosis of cirrhosis in either 775 or 1,007 patients. The cutoff value with optimal diagnosis accuracy was 14.6 kPa in 1,007 patients (positive and negative predictive values, 74% and 96%) with discrepancies among the etiological groups. Eighty patients were misclassified: (1) among 45 patients without cirrhosis with liver stiffness 14.6 kPa or greater, 27 (60%) had extensive fibrosis and 10 (22%) significant perisinusoidal fibrosis; and (2) among 35 patients with cirrhosis and liver stiffness less than 14.6 kPa, 10 (29%) had a macronodular pattern and 25 (71%) either none or mild activity. In conclusion , Fibroscan is a reliable method for the diagnosis of cirrhosis in patients with chronic liver diseases, better at excluding than at predicting cirrhosis using a threshold of 14.6 kPa. False-negatives are mainly attributable to inactive or macronodular cirrhosis.
Total genomic alteration as measured by SNP-array-based molecular karyotyping is predictive of overall survival in a cohort of MDS or AML patients treated with azacitidine
Authors: T Cluzeau, C Moreilhon, N Mounier, J-M Karsenti, L Gastaud, G Garnier, D Re, N Montagne, J Gutnecht, P Auberger, J G Fuzibet, J-P Cassuto, S Raynaud
Journal: Blood Cancer Journal (2013)

Metaphase cytogenetics (MC) has a major role in the risk stratification of patients with myelodysplastic syndromes (MDSs) and can affect the choice of therapies. Azacitidine (AZA) has changed the outcome of patients with MDS or acute myeloid leukemia (AML) unfit for intensive chemotherapy. Identification of patients without the benefit of AZA would allow AZA combination or other drugs in first-line treatments. New whole-genome scanning technologies such as single nucleotide polymorphism microarray (SNP-A)-based molecular karyotyping (MK) improve the risk stratification in MDS and AML. Maintenance of genomic integrity is less than three megabases (Mbs) total disruption of the genome correlated with better overall survival (OS) in patients with lower-risk MDS. In this SNP-A study, we aimed at defining a cutoff value for total genomic copy number (CN) alterations (TGA) influencing the median OS in a cohort of 51 higher-risk MDS/AML patients treated with AZA. We observed that the relative risk of worse OS increased >100 Mb of TGA, as detected by SNP-A-based MK (8 and 15 months respectively, P=0.02). Our data suggest that precise measurement of TGA could provide predictive information in poor and very poor revised International Prognostic Scoring system (IPSS-R) patients treated with AZA.
Primary Hyperparathyroidism: Pathology and Therapy
Authors: Edward Paloyan
Journal: JAMA (1981)

More than 50 years ago, despite the controversy over whether parathyroid tumors were harmful or not, Felix Mandl, a steadfast and determined Viennese surgeon, made his decision to operate on the now famous Albert, a tramcar conductor who had been bedridden with osteitis fibrosa cystica involving much of his skeleton. The good news was that Albert "stopped excreting his skeleton into his urine" and within a few months after his parathyroidectomy was able to ambulate and return to a relatively normal life. The bad news was not long in manifesting itself; a year or two later, Albert noticed recurrence of his symptoms and finally agreed to a second operation, six years after the first. Unfortunately, it was unsuccessful and Albert succumbed to the musculoskeletal and metabolic ravages of hyperparathyroidism. A reasonable assumption is that Albert had either "double adenomas," diffuse adenomatous hyperplasia, or multiglandular parathyroid disease. At least two lessons
A 73-Year-Old Man With Hearing Loss, 1 Year Later
Authors: Amy N. Ship
Journal: JAMA (2005)

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Arterial bypass surgery and smokers
Authors: J T Powell, R M Greenhalgh
Journal: BMJ (1994)

Whether smokers should be offered bypass surgery remains controversial despite the extensive airing the topic had in the BMJ's columns last year.1 Nearly all patients requiring such operations have smoked for long periods.2 Are there any benefits of giving up at this late stage?

With non-invasive techniques and objective markers of smoking it has been shown that one year after peripheral arterial bypass surgery the patency of femoropopliteal vein grafts in continuing smokers (63%) is significantly less than the patency of grafts in those who no longer smoke (84%).3 The results of prosthetic distal bypass surgery are similar - the chance of graft failure is doubled in smokers.4 Surveillance of the patency of coronary artery bypass grafts is more difficult, requiring serial angiography, and no study that has used objective markers of smoking has been reported. Nevertheless, some studies have reported an association between smoking and an increased risk of failed coronary bypass grafts.5,6 Continuing to smoke after surgery also has an adverse influence on the prognosis of aortofemoral bypass grafts.7

On …
Transition Zone Biopsy in the Detection of Prostate Cancer
Authors: Yasuyuki Kojima, Norio Nonomura, Takayuki Nose, Toshihiko Inoue, Kyou Tsuda, Yoshifumi Narumi, Hironobu Nakamura, Masaru Shin, Yutaka Yasunaga, Katsuyuki Aozasa, Tsuneharu Miki, Akihiko Okuyama
Journal: European Urology (2000)