tbuckley/cabot-search huggingface dataset:
Structure-Related Initiation of Reentry by Rapid Pacing in Monolayers of Cardiac Cells
Authors: Weining Bian, Leslie Tung
Journal: Circulation Research (2006)

This study examines how a zigzag pattern of conduction, a form of structural heterogeneity frequently found in old or diseased hearts, affects the vulnerability to reentry during rapid pacing. A central rectangular island (8x4 mm) containing a predefined zigzag pattern was created in cultured isotropic monolayers of neonatal rat ventricular myocytes. Impulse propagation was optically mapped from 253 sites using voltage-sensitive dye and was anisotropic within the zigzag island. With increasing interval between neighboring transverse connections (a), relative to the distance between longitudinal strands (b), transverse conduction velocity (CV) decreased to 66+/-6%, 20+/-2%, and 15+/-2% of CV in the surrounding isotropic region, whereas longitudinal CV increased to 102+/-8%, 113+/-12%, and 131+/-23% for a:b ratios of 1:1, 1:5, and 1:9, respectively. During rapid pacing, propagation distal to the island was steered from the side of the island with more transverse connections ("dominant" side) toward the side with fewer connections ("weak" side). Increased asymmetry in the pattern accentuated this effect, and resulted in increased rate-dependent differences in CV on the 2 sides. Consequently, a functional obstacle formed on the weak side, followed by development of single loop reentry. The reentrant wave revolved around a line of block defined by the border of the island. Reentry chirality was determined by the weak side location, and the pacing rate needed to initiate reentry decreased with increased asymmetry in the pattern. In conclusion, reentry is readily induced by rapid pacing in confluent cardiac cell monolayers containing a central and asymmetric island of zigzag conduction.
Comparison of visual and radiographic detection of bony changes at the knee joint.
Authors: J Rogers, I Watt, P Dieppe
Journal: BMJ (1990)

acute traumatic intracranial haematoma at all ages.Children with head injury can be managed by guidelines similar to those already used in adults, but to improve outcome even more patients should be investigated by computed tomography soon after injury.We therefore recommend that a patient with head injury who has either a persisting alteration in conscious level or a skull fracture should be investigated by computed tomography.The figure shows how this might be achieved through coordinated efforts by neurosurgical units and general hospitals with facilities for computed tomography.The box shows guidelines proposed as a basis for formulating new, locally agreed criteria for managing children and adults with head injuries.
Body concentration of caesium-137 in patients from Western Isles of Scotland.
Authors: C G Isles, I Robertson, J A Macleod, T Preston, B W East, D J Hole, A F Lever
Journal: BMJ (1991)

OBJECTIVES--To compare caesium-137 concentrations in patients from the Western Isles Health Board, Glasgow area, and other parts of the Scottish mainland, and to investigate the source of 137Cs in patients from the Western Isles. DESIGN--Study of hypertensive patients having electrolyte concentrations measured, including 137Cs. Interview by questionnaire of island subjects about intake of foods likely to contain radiocaesium and the source of these foods. Measurement of 137Cs and 134Cs in food, urine, and vegetation. SETTING--Scottish mainland and Western Isles, 1979-86. All measurements before Chernobyl nuclear accident. PATIENTS--413 consecutive patients referred to the blood pressure unit for investigation of hypertension. 60 from the Western Isles, including 44 from North Uist; 32 from North Uist participated in the dietary analysis. MAIN OUTCOME MEASURES--Concentration of radiocaesium in the body, urine, food, and vegetation. Islanders9 consumption of local produce. RESULTS--Patients from the Western Isles had five times higher body concentrations of 137Cs (median 2.54 (interquartile range 1.25-3.73)) Bq/gK) than did patients from around Glasgow (0.47 (0.26-0.66) Bq/gK) and other parts of the Scottish mainland (0.42 (0.24-0.71) Bq/gK). Islanders often consumed local milk and mutton, but ate local fish rarely. 137Cs and 134Cs were present in coastal (21.6 Bq/kg 137Cs, 0.25 Bq/kg 134Cs) and moorland (135.9, 0.65 Bq/kg) grasses and in islanders9 urine (2.01, 0.013 Bq/l). Lower concentrations (0.336, 0.004 Bq/l), were found in the urine of Glasgow controls (p less than 0.001 for both isotopes). CONCLUSIONS--Islanders have excess body 137Cs concentrations, most of which probably comes from local milk and lamb. The radioactivity is not above the recommended safety limit. The presence of 134Cs suggests that nuclear reprocessing is the source of some of the radiocaesium.
Effect of Clofibrate and Androsterone on Hypercholesterolaemic Xanthomatosis
Authors: B. Mason, C. B. Perry
Journal: BMJ (1965)

Aseptic Meningitis-Skoldenberg JOURNAL primary atypical pneumonia, but does not cause the meningitis.Of the two remaining cases one had right-sided pneumonia and the other pharyngotracheitis.The temporal association between cold-agglutinin-positive infection and aseptic meningoencephalitis or meningitis in the eight cases described is not definite evidence of an aetiological relation.The cases should, however, be noted in respect of the possibility of mycoplasma infection in aseptic meningo- encephalitis or meningitis, especially in cases without sign of atypical pneumonia. SummaryFrom January 1962 to June 1963 126 patients (69 females and 57 males) with cold-agglutinin-positive infection were treated at the Stockholm Hospital for Infectious Diseases.Eight of them (2 females and 6 males) had aseptic meningo- encephalitis or meningitis.Six of the eight patients were aged 5 to 29 years (75 of the total number of patients were in this age-group) and were among the 72 patients who fell ill between October 1962 and February 1963.It is suggested that Mycoplasma pneumoniae may be a cause of aseptic meningitis.
Matrix-immobilized fibroblast growth factor genes promoted angiogenesis in a porcine model of chronic myocardial ischemia
Authors: Kun-Lun He, Eva M. Becker, Geng-Hua Yi, Satoshi Mohri, Anguo Gu, Ge-Ping Zhang, Myung J. Lee, Jie Wang, Barbara A. Sosnowski, Glenn F. Pierce, John Doukas, Daniel Burkhoff
Journal: Journal of the American College of Cardiology (2003)
Early Dipyridamole <sup>99m</sup> Tc-Sestamibi Single Photon Emission Computed Tomographic Imaging 2 to 4 Days After Acute Myocardial Infarction Predicts In-Hospital and Postdischarge Cardiac Events
Authors: Kenneth A. Brown, Gary V. Heller, Ronald S. Landin, Leslee J. Shaw, George A. Beller, Michael J. Pasquale, Stephen B. Haber
Journal: Circulation (1999)

Background —Because of its brief hemodynamic effects and minor effect on determinants of myocardial oxygen demand, vasodilator stress myocardial perfusion imaging (MPI) can be applied very early after acute myocardial infarction (AMI) for risk stratification, allowing management decisions to be made earlier and thus potentially shortening hospitalization stays, reducing costs, and preventing early cardiac events. This multicenter randomized trial compared the prognostic value of early dipyridamole MPI and standard predischarge submaximal exercise MPI in patients who presented with AMI. Methods and Results —Patients who presented with their first AMI (n=451) were randomized in a 3:1 ratio to undergo either both an early (day 2 to 4) dipyridamole 99m Tc-sestamibi MPI study and a predischarge (day 6 to 12) submaximal exercise 99m Tc-sestamibi MPI study or only the predischarge study. Multivariate predictors of in-hospital cardiac events included nuclear imaging summed stress and summed reversibility scores and peak creatine kinase. For postdischarge cardiac events, multivariate predictors in patients undergoing dipyridamole MPI included only the summed stress, reversibility, and rest imaging scores and anterior MI. For a given summed stress score, the interaction of reversibility score further improved the predictive value. Dipyridamole MPI showed better risk stratification than submaximal exercise MPI. Conclusions —Dipyridamole MPI very early after MI predicts early and late cardiac events, with superior prognostic value compared with submaximal exercise imaging. The extent and severity of the stress defect and reversibility of the defect were the most important predictors of cardiac death and recurrent MI. This technique can allow management decisions to be made earlier with regard to AMI patients and could have important economic impact if applied widely.
The distribution of COPD in UK general practice using the new GOLD classification
Authors: John Haughney, Kevin Gruffydd-Jones, June Roberts, Amanda J Lee, Alison Hardwell, Lorcan McGarvey
Journal: European Respiratory Journal (2013)

The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 document recommends a combined assessment of chronic obstructive pulmonary disease (COPD) based on current symptoms and future risk. A large database of primary-care COPD patients across the UK was used to determine COPD distribution and characteristics according to the new GOLD classification. 80 general practices provided patients with a Read code diagnosis of COPD. Electronic and hand searches of patient medical records were undertaken, optimising data capture. Data for 9219 COPD patients were collected. For the 6283 patients with both forced expiratory volume in 1 s (FEV 1 ) and modified Medical Research Council scores (mean± sd age 69.2±10.6 years, body mass index 27.3±6.2 kg·m −2 ), GOLD 2011 group distributions were: A (low risk and fewer symptoms) 36.1%, B (low risk and more symptoms) 19.1%, C (high risk and fewer symptoms) 19.6% and D (high risk and more symptoms) 25.3%. This is in contrast with GOLD 2007 stage classification: I (mild) 17.1%, II (moderate) 52.2%, III (severe) 25.5% and IV (very severe) 5.2%. 20% of patients with FEV 1 ≥50% predicted had more than two exacerbations in the previous 12 months. 70% of patients with FEV 1 &lt;50% pred had fewer than two exacerbations in the previous 12 months. This database, representative of UK primary-care COPD patients, identified greater proportions of patients in the mildest and most severe categories upon comparing 2011 versus 2007 GOLD classifications. Discordance between airflow limitation severity and exacerbation risk was observed.
HDAC Inhibition Overcomes Acute Resistance to MEK Inhibition in <i>BRAF</i>-Mutant Colorectal Cancer by Downregulation of c-FLIPL
Authors: Robbie Carson, Basak Celtikci, Cathy Fenning, Arman Javadi, Nyree Crawford, Lucia Perez-Carbonell, Mark Lawler, Daniel B. Longley, Patrick G. Johnston, Sandra Van Schaeybroeck
Journal: Clinical Cancer Research (2015)

Activating mutations in the BRAF oncogene are found in 8% to 15% of colorectal cancer patients and have been associated with poor survival. In contrast with BRAF-mutant (MT) melanoma, inhibition of the MAPK pathway is ineffective in the majority of BRAFMT colorectal cancer patients. Therefore, identification of novel therapies for BRAFMT colorectal cancer is urgently needed.BRAFMT and wild-type (WT) colorectal cancer models were assessed in vitro and in vivo. Small-molecule inhibitors of MEK1/2, MET, and HDAC were used, overexpression and siRNA approaches were applied, and cell death was assessed by flow cytometry, Western blotting, cell viability, and caspase activity assays.Increased c-MET-STAT3 signaling was identified as a novel adaptive resistance mechanism to MEK inhibitors (MEKi) in BRAFMT colorectal cancer models in vitro and in vivo. Moreover, MEKi treatment resulted in acute increases in transcription of the endogenous caspase-8 inhibitor c-FLIPL in BRAFMT cells, but not in BRAFWT cells, and inhibition of STAT3 activity abrogated MEKi-induced c-FLIPL expression. In addition, treatment with c-FLIP-specific siRNA or HDAC inhibitors abrogated MEKi-induced upregulation of c-FLIPL expression and resulted in significant increases in MEKi-induced cell death in BRAFMT colorectal cancer cells. Notably, combined HDAC inhibitor/MEKi treatment resulted in dramatically attenuated tumor growth in BRAFMT xenografts.Our findings indicate that c-MET/STAT3-dependent upregulation of c-FLIPL expression is an important escape mechanism following MEKi treatment in BRAFMT colorectal cancer. Thus, combinations of MEKi with inhibitors of c-MET or c-FLIP (e.g., HDAC inhibitors) could be potential novel treatment strategies for BRAFMT colorectal cancer.
Activism in Academic Internal Medicine
Authors: Robert Glickman, J. Claude Bennett, James Nolan, John Stobo, Arthur Rubenstein, Jim Terwilliger
Journal: Annals of Internal Medicine (1992)

Editorials1 August 1992Activism in Academic Internal MedicineRobert Glickman, MD, J. Claude Bennett, MD, James Nolan, MD, John Stobo, MD, Arthur Rubenstein, MD, Jim TerwilligerRobert Glickman, MDSearch for more papers by this author, J. Claude Bennett, MDSearch for more papers by this author, James Nolan, MDSearch for more papers by this author, John Stobo, MDSearch for more papers by this author, Arthur Rubenstein, MDSearch for more papers by this author, Jim TerwilligerSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-117-3-259 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn a past issue of this journal, the Association of Professors of Medicine (APM) was identified as an organization with "the power to effect change because it has the authority, responsibility, and accountability for the academic departments of medicine" but also as never having assumed a leadership role for internal medicine. The APM is now taking actions that will address this assertion. One issue where leadership is needed is in the growing imbalance between generalists and subspecialists in internal medicine.The Association of Professors of Medicine recently passed a resolution supporting the goal of producing 50% general internists from internal medicine residency training programs.The APM adopts as a goal the entry of 50 percent of the internal medicine residency graduates into the practice of general internal...Reference1. Reitemeier R. The leadership crisis in internal medicine: what can be done? Ann Intern Med. 1991;114:69-75. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byWomen’s health and enhancing generalism in internal medicineDepartments of Medical Specialties: A Solution for the Divergent Missions of Internal Medicine?Cardiovascular medicine: Subspecialty or specialtyPrimary Care and the Affliction of Internal MedicineThe Downsizing of Internal Medicine Residency ProgramsDavid A. Asch, MD, MBA, Jack Ende, MD 1 August 1992Volume 117, Issue 3Page: 259-260KeywordsAcademic medicineGraduate medical educationResidencySub-specialty care ePublished: 1 December 2008 Issue Published: 1 August 1992 PDF downloadLoading ...
Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta.
Authors: F Randow, U Syrbe, C Meisel, D Krausch, H Zuckermann, C Platzer, H D Volk
Journal: The Journal of Experimental Medicine (1995)

Tolerance of monocytes/macrophages to endotoxin (lipopolysaccharide [LPS]) can be induced both in vivo and in vitro by LPS itself. Exposure to LPS, even at a very low dose, induces a downregulation of cytokine response to a second high dose LPS challenge. To learn more about the unknown mechanisms of this phenomenon, we studied the role of antiinflammatory cytokines in this process. Preculture of human peripheral blood monocytes for 24 hours with low concentrations of LPS induced hyporesponsiveness to high-dose LPS rechallenge with respect to tumor necrosis factor (TNF) alpha and interleukin (IL) 10 but not IL-1RA production. These results suggest that LPS tolerance reflects a functional switch of monocytes rather than a general LPS hyporesponsiveness. IL-10 and transforming growth factor (TGF) beta 1 showed additive effects in replacing LPS for induction of LPS hyporesponsiveness in vitro. Additionally, neutralizing anti-IL-10 and anti-TGF-beta monoclonal antibodies prevented induction of LPS tolerance. In vitro induced LPS tolerance looks like the ex vivo LPS hyporesponsiveness of monocytes from septic patients with fatal outcome: downregulation of LPS-induced TNF-alpha and IL-10 production but not of IL-1RA secretion. LPS hyporesponsiveness in septic patients was preceded by expression of IL-10 at both the mRNA and protein level. In summary, our data suggests that IL-10 and TGF-beta mediate the phenomenon of LPS tolerance in vitro and perhaps in vivo (septic patients), too.
Mortality From Myocardial Infarction
Authors: Byron Monroe
Journal: JAMA (1982)

<h3>To the Editor.—</h3> It is not surprising to me that neither Weinblatt et al (1982; 247:1576) nor Goldberg et al<sup>1</sup>were able to demonstrate that care after myocardial infarction (MI) was a significant reason for the drop in mortality from this disease during the late 60s and early 70s. It is more difficult to mend a broken egg (heart), than it is to prevent it from breaking. In the course of time, preventive measures will most likely be found to be the reason for this drop in mortality. The editorial comment by Dr Havlik (1982;247:1605) that accompanied the article by Weinblatt and co-workers, that this will be a "bitter pill" for those who have hoped that improved care<i>after</i>MI would be the main reason for the decline in cardiovascular mortality, is probably true. It is also sad that this may come as a surprise to many physicians. Currently, it
Uterine Uptake of lodine-123 Metaiodobenzylguanidine during the Menstrual Phase of Uterine Cycle
Authors: J BOMANJI, K E BRITTON
Journal: Clinical Nuclear Medicine (1987)

Radioiodinated I-123 metaiodobenzylguanidine (MIBG) has been used for diagnostic purposes for detection of apudomas. In this paper normal physiological uptake of I-123 MIBG by the uterus during the menstrual phase of the uterine cycle is reported. It is likely that I-123 MIBG can be used to evaluate some of the problems in this context.
A Novel Type of p53 Pathway Dysfunction in Chronic Lymphocytic Leukemia Resulting from Two Interacting Single Nucleotide Polymorphisms within the <i>p21</i> Gene
Authors: Gillian G. Johnson, Paul D. Sherrington, Anthony Carter, Ke Lin, Triantafillos Liloglou, John K. Field, Andrew R. Pettitt
Journal: Cancer Research (2009)

Abstract The ATM-p53 pathway plays an important role in the biology of chronic lymphocytic leukemia (CLL). Its functional integrity can be probed by exposing CLL cells to ionizing radiation (IR) and measuring levels of p53 protein and one of its transcriptional targets, the cyclin-dependent kinase inhibitor p21. We have previously identified two abnormal p53/p21 response patterns associated with inactivating mutations of TP53 and ATM, respectively. Here, we describe a third abnormal response pattern characterized by failure of p21 protein accumulation despite a normal p53 protein response. This so-called "type C" response was detected in 10.6% of unselected patients and was associated with resistance of CLL cells to p53-dependent killing by IR, with the clinically more aggressive variant of CLL characterized by unmutated immunoglobulin heavy-chain genes and with a single nucleotide polymorphism at codon 31 of the p21 gene in which Ser is replaced by Arg. CLL samples with this allelic variant displayed impaired IR-induced up-regulation of total p21 mRNA and did not express the Arg-encoding transcript, except in those cases harboring an additional single nucleotide polymorphism (T instead of C) in the 3′-untranslated region of the same p21 allele. Our data provide new insight into the importance of p21 in CLL biology. [Cancer Res 2009;69(12):5210–17]
Renal Failure, Rhabdomyolysis, and Phenylpropanolamine
Authors: George A. Blewitt
Journal: JAMA (1983)

<h3>To the Editor.—</h3> We have reviewed the article by Swenson and colleagues entitled "Acute Renal Failure and Rhabdomyolysis After Ingestion of Phenylpropanolamine-Containing Diet Pills" (1982;248:1216) and offer the following comments. The authors cite reports of "amphetaminelike" CNS stimulation and hypertension as being associated with ingestion of phenylpropanolamine hydrochloride. Several controlled clinical studies, however, have<i>not</i>shown these effects in a cross section of human volunteers at allowed therapeutic doses. Previous publications referred to in this article do not support such adverse affects associated with<i>responsible</i>use of phenylpropanolamine-containing drug products.<sup>1,2</sup>Indeed, another reference is a case report of an attempted suicide with a phenylpropanolamine-containing diet aid at<i>34 times</i>the normal dose.<sup>3</sup>Reference 6 referred to five patients who had injected by the intravenous route a "homemade" dosage form of<i>amphetamine</i>.<sup>4</sup>Clearly, there is nothing in the article in common with these reports and the purported side
RENAL HYPERTENSION IN RATS IMMUNIZED AGAINST ANGIOTENSIN I AND ANGIOTENSIN II
Authors: Helen F. Oates, Gordon S. Stokes, Brian G. Storey, Robyn G. Glover, Beverley F. Snow
Journal: The Journal of Experimental Medicine (1974)

Rats, actively immunized against angiotensin I (AI) and angiotensin II (AII), were subjected to unilateral renal artery constriction to determine whether the resulting hypertension, which may still ensue in the animal immunized against AII, could be prevented by such combined immunity. Sustained immunity to both AI and AII neither changed preoperative blood pressures of the rats from those of control mock-immunized rats nor altered the incidence or severity of renal dip hypertension. Vascular hyperresponsiveness to small quantities of free angiotensin could not be invoked to explain the hypertension, for there was no significant difference between mock-immunized hypertensive animals, and those remaining normotensive, regarding pressor sensitivity to intravenous AI, AII, renin, and norepinephrine. (AI + AII)-immunized hypertensive rats required AI doses averaging 260 times greater than nonimmune hypertensives to elicit equipressor responses, and were refractory to renin, but not to norepinephrine. Thus, while previous studies have not excluded direct participation of endogenous AI in renal clip hypertension in rats, evidence from our experiments makes it extremely difficult to sustain any pressor function therein for circulating AI or AII. Our results also preclude involvement of AII produced from circulating AI by conversion within arteriolar walls, close to receptor sites, since AI immunity would block this mechanism of action.
Municipal Engineering and Sanitation.
Authors: Moses Nelson Baker
Journal: JAMA (1902)

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