tbuckley/cabot-search huggingface dataset:
Development of Decompensated Dilated Cardiomyopathy Is Associated With Decreased Gene Expression and Activity of the Milrinone-Sensitive cAMP Phosphodiesterase <i>PDE3A</i>
Authors: Carolyn J. Smith, Raymond Huang, Dong Sun, Sidonnie Ricketts, Carl Hoegler, Jia-Zhen Ding, Richard A. Moggio, Thomas H. Hintze
Journal: Circulation (1997)

Background Phosphodiesterase III (PDE3) inhibitors are inotropic agents used to treat congestive heart failure (CHF) and are less effective in patients with severe CHF. Little is known about relative changes in PDE3 activity or gene expression during the evolution of cardiomyopathy. Methods and Results In the present study, we evaluated temporal changes in PDE3A gene expression before and after pacing-induced CHF in nine mongrel dogs. Three weeks of left ventricular (LV) pacing produced LV end-diastolic pressures of 15±1.7 mm Hg, whereas overt CHF at 4 to 5 weeks was associated with LV end-diastolic pressures of 24±1.7 mm Hg; prepacing values were 6.6±0.6 mm Hg. Total RNA isolated from LV tissues was analyzed on Northern blots; 10 unpaced normal hearts served as tissue controls. Signals for PDE3A mRNAs (7, 8, and 10 kb) or PDE4D (7.6 kb) were normalized against glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ) or ribosomal 18S RNA. Before the onset of CHF, PDE3A / GAPDH ratios were not different between the control and 3-week paced groups. In contrast, all PDE3A / GAPDH ratios were selectively reduced by 52%, and PDE3A /18S was reduced by 70% ( P &lt;.05) in CHF; PDE4D / GAPDH (or 18S) was unchanged. LV tissues from four control and four CHF dogs were also processed to isolate cytosolic and microsomal membrane protein for cAMP PDE3 activity assays. CHF was associated with a significant 54% reduction ( P &lt;.05) in microsomal but not cytosolic PDE3 activity. Conclusions Selective downregulation of PDE3A may account in part for the ineffectiveness of milrinone in the treatment of severe CHF.
Modulation of crossbridge kinetics by myosin isoenzymes in skinned human heart fibers.
Authors: I Morano, C Bletz, R Wojciechowski, J C Rüegg
Journal: Circulation Research (1991)

Skinned fibers from the normal human heart with the beta-myosin heavy chain (ventricular fibers) revealed both a higher force generation per cross section and a higher Ca2+ sensitivity than skinned fibers with the alpha-myosin heavy chain (atrial fibers). The relation between isometric ATPase activity and isometric tension of atrial fibers was higher than that of ventricular fibers. Since the ATPase-tension relation equals the rate constant for the transition from force-generating into non-force-generating crossbridge states (g(app)), myosin heavy chain isoenzymes seem to have different crossbridge turnover kinetics. Modulation of g(app) by myosin heavy chain isoenzymes could explain the different contractile behavior of atrial and ventricular fibers. g(app) was independent of Ca2+.
Activists in India are promoting good health of babies through breast feeding
Authors: N B Kumta
Journal: BMJ (1997)

Editor–I was shocked to read the unkind comments made by John Dobbing in his letter1 about the editorial by R K Anand.2

I was the organiser of the international workshop in Bombay on the prevention of mental handicap in developing countries under the aegis of the Commonwealth Association for Mental Handicap and Developmental Disabilities, to which Dobbing refers. The entire proceedings were published in Bombay …
Novel MicroRNA Prosurvival Cocktail for Improving Engraftment and Function of Cardiac Progenitor Cell Transplantation
Authors: Shijun Hu, Mei Huang, Patricia K. Nguyen, Yongquan Gong, Zongjin Li, Fangjun Jia, Feng Lan, Junwei Liu, Divya Nag, Robert C. Robbins, Joseph C. Wu
Journal: Circulation (2011)

Background— Although stem cell therapy has provided a promising treatment for myocardial infarction, the low survival of the transplanted cells in the infarcted myocardium is possibly a primary reason for failure of long-term improvement. Therefore, the development of novel prosurvival strategies to boost stem cell survival will be of significant benefit to this field. Methods and Results— Cardiac progenitor cells (CPCs) were isolated from transgenic mice, which constitutively express firefly luciferase and green fluorescent protein. The CPCs were transduced with individual lentivirus carrying the precursor of miR-21, miR-24, and miR-221, a cocktail of these 3 microRNA precursors, or green fluorescent protein as a control. After challenge in serum free medium, CPCs treated with the 3 microRNA cocktail showed significantly higher viability compared with untreated CPCs. After intramuscular and intramyocardial injections, in vivo bioluminescence imaging showed that microRNA cocktail-treated CPCs survived significantly longer after transplantation. After left anterior descending artery ligation, microRNA cocktail-treated CPCs boost the therapeutic efficacy in terms of functional recovery. Histological analysis confirmed increased myocardial wall thickness and CPC engraftment in the myocardium with the microRNA cocktail. Finally, we used bioinformatics analysis and experimental validation assays to show that Bim, a critical apoptotic activator, is an important target gene of the microRNA cocktail, which collectively can bind to the 3′UTR region of Bim and suppress its expression. Conclusions— We have demonstrated that a microRNA prosurvival cocktail (miR-21, miR-24, and miR-221) can improve the engraftment of transplanted cardiac progenitor cells and therapeutic efficacy for treatment of ischemic heart disease.
Oxymetholone and Hematologic Disease
Authors: A. D. GINSBURG
Journal: Annals of Internal Medicine (1973)

Comments and Corrections1 December 1973Oxymetholone and Hematologic DiseaseA. D. GINSBURG, M.D. F.R.C.P. (C)A. D. GINSBURG, M.D. F.R.C.P. (C)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-6-914_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: With regard to the comment by Dr. C. R. Kjeldsberg (Ann Intern Med79:288, 1973), that the report of Delamore and Geary (1) constitutes the only association of leukemia with oxymetholone therapy, may I draw attention to two other papers. In 19 patients with various types of refractory anemia treated with oxymetholone, 2 developed acute myeloblastic leukemia and one, a lymphoma (2). King and Burns (3) have described a patient who, 3 months after a short course of chloramphenicol, developed aplastic anemia, which responded to oxymetholone but was followed by the development of acute myeloblastic leukemia 4...References1. DELAMOREGEARY IC: Aplastic anaemia, acute myeloblastic leukaemia and oxymetholone. Brit Med J 2:743-745, 1971 CrossrefMedlineGoogle Scholar2. SACKSGALEBOTHWELL PDT: Oxymetholone therapy in aplastic and other refractory anaemias. S Afr Med J 46:1607-1615, 1972 MedlineGoogle Scholar3. KINGBURNS JD: Aplastic anaemia, oxymetholone and acute myeloid leukaemia. Ibid., pp. 1622-1623 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine Queen's University Kingston, Ontario Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTreatment of Refractory Anemias with Methenolone 1 December 1973Volume 79, Issue 6Page: 914-914KeywordsAcute myeloid leukemiaAnemiaAplastic anemiaBurnsChloramphenicolLymphoma Issue Published: 1 December 1973 PDF downloadLoading ...
Abstract ES4-3: Risk of Developing Second Primary Breast Cancer among Survivors of Breast Cancer
Authors: JL Bernstein
Journal: Cancer Research (2012)

Abstract Of the nearly 226,870 US women expected to develop breast cancer in 2012 and the over 3 million breast cancer survivors currently residing in the US, five to ten percent will develop a subsequent primary in the contralateral breast (CBC) (www.cancer.org). This risk of developing CBC is higher than the overall risk of breast cancer in the general population. The rising incidence of breast cancer, coupled with an improved survival potential after cancer diagnosis has placed an increased number of women at risk for CBC, yet the epidemiology is poorly understood. Despite common genetics and exposures shared by both breasts, only a fraction of women who survive their first primary will develop a second primary in the contralateral breast. Epidemiologic studies have identified factors associated with an increased risk of developing CBC, including family history of breast cancer, early age at diagnosis, hormonal factors, reproductive history, body-mass index, and tumor characteristics of the first primary e.g., lobular histology, stage and estrogen receptor (ER) status. The risk of developing CBC has also been associated with mutations of specific genes including BRCA1, BRCA2, and CHEK2. Importantly, the treatment a woman receives for her first primary breast cancer can also influence her risk of developing CBC; chemotherapy, hormonal therapies and tamoxifen significantly reduces the risk of developing CBC while the radiation received to the contralateral breast during radiotherapy increases the risk of CBC. Despite the number of established risk factors for increased CBC risk, their combined effect accounts for only a small portion of the CBCs that develop each year. It is unclear whether, and to what extent, genetic factors and radiation, individually or via interaction, contribute to the development of CBC. This talk will review the state of the field. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr ES4-3.
Locating Pheochromocytomas by Scintigraphy Using 131I-Metaiodobenzylguanidine
Authors: J. C. Sisson, B. Shapiro, W. H. Beierwaltes, J. E. Copp
Journal: CA A Cancer Journal for Clinicians (1984)

Scintigraphy with 131I-MIBG has located most pheochromocytomas. The detected tumors have been intra-adrenal, extra-adrenal, malignant, and familial in type. The method is safe, but requires images taken over three days to attain optimal results. Because of its ability to screen all sites where primary pheochromocytomas may reside, scintigraphy should be employed as the initial procedure in the search for these tumors. It may be the only technique that will locate extra-adrenal pheochromocytomas. The rate of false-negative results is about 10 percent; therefore, other techniques such as computed tomography will be necessary to help find the few elusive pheochromocytomas.
Role of coronary artery spasm in progression of organic coronary stenosis and acute myocardial infarction in a swine model. Importance of mode of onset and duration of coronary artery spasm.
Authors: T Kuga, H Tagawa, H Tomoike, W Mitsuoka, S Egashira, Y Ohara, A Takeshita, M Nakamura
Journal: Circulation (1993)

BACKGROUND Coronary spasm may play an important role in progression of organic coronary stenosis and myocardial infarction, but the mechanisms responsible for these complications are not known. This study aimed to examine whether the mode of onset and the duration of coronary spasm influenced progression of organic coronary stenosis and acute myocardial infarction in a swine model of coronary spasm. METHODS AND RESULTS Göttingen miniature pigs were subjected to cholesterol feeding, balloon-induced coronary arterial denudation, and x-ray irradiation. Five months later, coronary spasm was induced by intracoronary injection of serotonin. In 10 pigs, coronary spasm was provoked abruptly and maintained for 25 minutes by five repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes (group A, abrupt onset and short duration). In group B, coronary spasm was provoked gradually by intracoronary injections of serotonin at graded doses of 0.1, 0.3, and 0.6 microgram/kg every 5 minutes and was then maintained for 25 minutes in four pigs (group B1, gradual onset and short duration) and for 120 minutes in six pigs (group B2, gradual onset and long duration) by repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes. Intramural hemorrhage was noted histologically at the spastic site more frequently in group A with abrupt onset (nine of 10 pigs) than in group B with gradual onset (two of 10 pigs) (p &lt; 0.01). Progression of organic coronary stenosis due to intramural hemorrhage was noted in seven pigs (six pigs in group A and one pig in group B), including three cases of total coronary occlusion. Evidence for the evolution of acute myocardial infarction (serial ECG findings, left ventriculograms, and histological findings) was noted in one pig (7%) of group A or B1 with short duration and in five of six pigs (83%) in group B2 with long duration (p &lt; 0.01 versus group A and B1). CONCLUSIONS These results indicate that: 1) intramural hemorrhage was frequently induced by coronary spasm of abrupt but not of gradual onset, 2) intramural hemorrhage resulted in acute progression of coronary stenosis and sometimes resulted in persistent total coronary occlusion leading to acute myocardial infarction, and 3) prolonged coronary spasm resulted in acute myocardial infarction without progression of organic coronary stenosis.
Imipenem: First of a New Class of Beta-Lactam Antibiotics
Authors: MICHAEL BARZA
Journal: Annals of Internal Medicine (1985)

Imipenem, the first of a new class of carbapenem antibiotics, has potent activity against most clinically important species of bacteria, including isolates resistant to other antibiotics. The drug is well distributed to most tissues and fluids after intravenous administration; however, levels in cerebrospinal fluid are modest. Most of the drug is eliminated in the urine, where it is metabolized by an enzyme on the brush border of the renal tubular cells; cilastatin is given simultaneously to inhibit this inactivation. Adverse effects include a syndrome of nausea and hypotension, especially after rapid intravenous infusion, and a predisposition to seizures in certain high-risk patients. Superinfections by resistant bacteria and fungi are infrequent. This new drug may be particularly useful in the treatment of infections caused by mixtures of bacteria for which a combination of antibiotics, often including an aminoglycoside, would otherwise be necessary. Examples include pulmonary, intra-abdominal, and soft-tissue infections.
Acute Coronary Care: Principles and Practice
Authors: Samuel Zoneraich
Journal: JAMA (1986)

A comprehensive text on acute coronary care represents a significant event for those active in the field. At first glance, it would appear that the message of this authoritative book is much delayed. After all, coronary care units (CCUs) have been around for two decades. However, a good book was lacking. The delay, however, is compensated for by the possibilities we now have to look back and to assess and reassess the value and the limitations of such units, their use and misuse, and the advantages and the limitations of some techniques. The book is divided into ten sections on these topics: pathophysiology, prediction and prevention of acute myocardial ischemia and infarction, diagnosing and sizing myocardial infarction, monitoring, and coronary care: the prehospital phase, the postadmission phase, the coronary care unit, the coronary care unit phase, the predischarge phase, and the convalescent phase. Many authors are authorities in their particular
The Histological Basis of Detection of Adenoma and Cancer in the Colon by Autofluorescence Endoscopic Imaging
Authors: K. Izuishi, H. Tajiri, T. Fujii, N. Boku, A. Ohtsu, T. Ohnishi, M. Ryu, T. Kinoshita, S. Yoshida
Journal: Endoscopy (1999)

The reason for the difference in fluorescence between normal and diseased tissues (carcinoma and adenoma) in the colon observed on autofluorescence endoscopy is unclear, flavins, NADPH and collagen being regarded as possible major sources of fluorescence. The purpose of this study was to identify the reason for this difference in fluorescence.Samples of human colonic tissues (adenoma: n = 6, cancer: n = 11, normal: n = 11) were obtained from resected specimens. The flavin content of human colonic tissue was measured by high performance liquid chromatography. Fluorescence microscopy under blue light excitation (400-440 nm) was performed using frozen sections of normal, adenomatous and cancerous tissues, and examining them for the presence and characteristics of fluorescence.The flavin content of normal and diseased tissue was not significantly different. Fluorescence microscopy of normal colonic tissue revealed strong fluorescence in the submucosal layer, which corresponded to collagen. Tissue fluorescence did not decrease in reducing agent or acid solution. No difference in fluorescence was detected in normal mucosa, adenoma or cancerous tissue on fluorescence microscopy. These findings indicate that flavins and NADPH do not affect tissue fluorescence, and that submucosal collagen is the main source of tissue fluorescence in the colon.The reason for the decreased fluorescence in diseased tissues appears to be a decrease in collagen fluorescence due to the screening effect of mucosal thickening or replacement of submucosa by cancer cells.
Reduction in Carotid Intima-Media Thickness After Pancreatic Islet Transplantation in Patients With Type 1 Diabetes. Diabetes Care 2013;36:450-456
Authors: K. K. Danielson, B. Hatipoglu, K. Kinzer, B. Kaplan, J. Martellotto, M. Qi, A. Mele, E. Benedetti, J. Oberholzer
Journal: Diabetes Care (2014)

In the print version of the article listed above, the following sentence should have been included in …
CAUSES, TYPES AND TREATMENT OF DIARRHEA IN ADULT LIFE
Authors: RICHARD C. CABOT
Journal: JAMA (1913)

We have undertaken a fresh study of this ancient problem, beginning with the necropsy records of Bellevue Hospital in New York and the Massachusetts General Hospital in Boston. In each of these institutions we examined three thousand necropsy records, searching for lesions ordinarily supposed to produce diarrhea. We then traced the cases showing these lesions back to the clinical records, trying to ascertain first whether the lesions actually produced diarrhea, and if so, in what proportion of cases; secondly, whether any special type of symptoms or of discharges was associated with any special lesion of the intestine, the endeavor being to mark out clinical types so far as this was possible. Finally, we reviewed the results of treatment both in necropsy cases and in a considerable series of cases which did not come to necropsy, and endeavored to estimate the value of the different methods used. For various reasons we have excluded from this study certain
Statin-Associated Myopathy
Authors: Paul D. Thompson, Priscilla Clarkson, Richard H. Karas
Journal: JAMA (2003)

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are associated with skeletal muscle complaints, including clinically important myositis and rhabdomyolysis, mild serum creatine kinase (CK) elevations, myalgia with and without elevated CK levels, muscle weakness, muscle cramps, and persistent myalgia and CK elevations after statin withdrawal. We performed a literature review to provide a clinical summary of statin-associated myopathy and discuss possible mediating mechanisms. We also update the US Food and Drug Administration (FDA) reports on statin-associated rhabdomyolysis. Articles on statin myopathy were identified via a PubMed search through November 2002 and articles on statin clinical trials, case series, and review articles were identified via a PubMed search through January 2003. Adverse event reports of statin-associated rhabdomyolysis were also collected from the FDA MEDWATCH database. The literature review found that reports of muscle problems during statin clinical trials are extremely rare. The FDA MEDWATCH Reporting System lists 3339 cases of statin-associated rhabdomyolysis reported between January 1, 1990, and March 31, 2002. Cerivastatin was the most commonly implicated statin. Few data are available regarding the frequency of less-serious events such as muscle pain and weakness, which may affect 1% to 5% of patients. The risk of rhabdomyolysis and other adverse effects with statin use can be exacerbated by several factors, including compromised hepatic and renal function, hypothyroidism, diabetes, and concomitant medications. Medications such as the fibrate gemfibrozil alter statin metabolism and increase statin plasma concentration. How statins injure skeletal muscle is not clear, although recent evidence suggests that statins reduce the production of small regulatory proteins that are important for myocyte maintenance.
PTH-151 Are the current management strategies for T1/T2 n0 oesophageal cancer optimal?
Authors: R Evans, JP Evans, G Kirby, F Curran, CVN Cheruvu
Journal: Gut (2015)

<h3>Introduction</h3> Stage directed therapy based on the imaging modalities remains the cornerstone of oesophageal cancer management. EUS and CT imaging are the commonly used modalities to stage patients with oesophageal cancer, with sensitivity of 90% and 70% for T staging respectively; EUS provides up to 70% accuracy in N stage. Neoadjuvant chemotherapy is recognised to reduce 3-yr mortality in the patients with stage II/III oesophageal cancers. Due to the limitations in the preop staging modalities, a cohort of patients with preop T1/2 risk being under staged and have surgery as the index treatment option, who may have otherwise benefited from neoadjuvant therapy. We aim to assess the number of patients who had stage migration following oesophagectomy having being staged as T1/T2 and N0 preoperatively. <h3>Method</h3> This study includes a cohort of consecutive patients who had oesophagectomy between 2008–2014. EUS, CT and PET scanning of all patients’ results were reviewed, with emphasis on those with T1/T2 N0 disease. Data on patients with T1/T2 N0 disease who went straight to surgery was analysed. The primary end points include staging migration on post-operative histology, perioperative mortality, morbidity and survival. <h3>Results</h3> In the 6-yr study period, 330 oesophagectomies were performed of which 62 patients had preoperative T1/2 N0 disease (18.7%); 20 patients with T1 N0 and 42 patients with T2 N0. The median age was 64 years (range 46–81) and 46 (74.1%) of the patients were male. Amongst these, 56 patients had Ivor-Lewis oesophagectomies, MIOs in 3 and 3 had a trans-hiatal operations with curative intent. Median length of stay was 13 days (range 7–97) whilst minor and major complications occurred in 43.5% (n = 27). Postoperative deaths occurred in 3 patients (4.8%) during their index admission as a result of (anastamotic leak (1), bowel ischaemia (1) and stroke (1)). Amongst the 62 with preoperative T1/T2 disease, postoperative stage migration was found in 25 (40.3%) patients who were upstaged to pT3 disease (13 patients). Nodal disease was found in 20 patients while 8 patients had R1 resections. A cohort of these patients had adjuvant therapy. In our cohort, 6 died (mean 795 days, range 181–1545). The remaining two patients had no recurrence at 455 and 804 days post surgery. In total, 14 patients received adjuvant treatment; 9 patients developed recurrence (median 557 days, range 303–1336) and 13 patients died during their follow up (median 400 days post op, range 8–1545). To date, 41 patients remain under follow up with median survival of 879 day (range 160–2363 days). <h3>Conclusion</h3> This study concludes that there were a significant number of people who were under staged and were not offered potentially curative treatment options. <h3>Disclosure of interest</h3> None Declared.