tbuckley/cabot-search huggingface dataset:
Presidential Disability and the Twenty-fifth Amendment
Authors: Richard A. Friedman
Journal: JAMA (1995)

To the Editor.  —The discussion about the attempted assassination of President Reagan focused on the implications of presidential disability due to major medical illness. 1 However, the role of psychiatric illness in presidential disability was conspicuously absent from this discussion.  Psychiatric illnesses such as anxiety disorders, mood disorders, and alcohol and substance abuse are a common source of morbidity and disability in the US population; the president too is vulnerable to psychiatric illness. Unfortunately, there is strong recent evidence from the Epidemiologic Catchment Area survey sponsored by the National Institute of Mental Health that only 28% of Americans with a mental disorder receive any treatment. 2   Unrecognized and untreated psychiatric illness in the president can have profound adverse domestic and international political effects, aside from personal morbidity. For example, a president suffering from depression may experience significant cognitive deficits, lack of motivation, and disabling fatigue.  Dementias like Alzheimer's disease and
Decreased vascular and increased adrenal and renal sensitivity to angiotensin II in the newborn lamb.
Authors: S RSiegel
Journal: Circulation Research (1981)

The effects of two doses of angiotensin II (0.025 micrograms/kg per min and 0.25 micrograms/kg per min) on plasma renin activity (PRA), aldosterone concentration, creatinine clearance, and sodium and potassium excretion were studied in two groups of 2- to 3-week-old lambs. The 0.025 micrograms/kg per min dose of angiotensin II also was studied in six adult ewes. In response to the angiotensin II infusions, PRA decreased in the newborns from baselines of 24.5 +/- 2.3 ng/ml per hr (mean +/- SE) and 22.9 +/- 3.5 to 13.6 +/- 0.8 and 13.0 +/- 2.2 at 30 minutes (P < 0.01), respectively, and returned to baseline at 60 minutes; PRA decreased from 1.7 +/- 0.1 to 0.95 +/- 0.3 ng/ml per hr at 30 minutes (P < 0.01) in the ewe and returned to baseline at 60 minutes. Plasma aldosterone increased in the newborns from baselines of 17.4 +/- 5.0 ng/dl and 14.7 +/0 3.9 to 33.1 +/- 6.9 and 32.5 +/- 6.3, respectively, at 15 minutes (P < 0.01) and returned to baseline at 60 minutes. Plasma aldosterone increased from 4.3 +/- 0....
Reply:
Authors: Sigal Kremer‐Tal, Helen Reeves, Goutham Narla, John Martignetti, Scott Friedman
Journal: Hepatology (2005)

We appreciate the interest of Drs. Boyault and colleagues in the potential role of KLF6 in hepatocellular cancer (HCC). As we have previously outlined,1 somatic mutation detection in cancer can be highly variable owing to differences in methodology and sample sets. Indeed, reported mutational frequencies of even well-characterized tumor suppressor genes—for example, p53—can range from 13%-67% in HCC.2 Similarly, in prostate cancer, whereas one study failed to identify KLF6 mutations,3 a second one apart from our own4 identified loss of heterozygosity (LOH) in approximately 30% of samples and somatic mutations in 15%.5 In contrast to the negative findings suggested by Drs. Boyault and colleagues, a recent publication6 has identified KLF6 LOH and mutation in HCC at levels almost identical to those we originally reported.7 We would also emphasize that LOH of the KLF6 locus is present much more commonly than mutation in HCC.6, 7 This result parallels the published findings in other cancers, including prostate,4, 5 colorectal,8 and non–small cell lung cancer.9 This feature was not examined by Drs. Boyault and colleagues even though it may lead to a growth advantage through haploinsufficiency. Interestingly, we have also defined a number of tumors that demonstrate only significant degrees of LOH, without somatic mutation. These include ovarian cancer, head and neck squamous cell carcinoma, small cell lung cancer, and glioblastoma, as well as prostate cancer cell lines (manuscripts in preparation), suggesting that the presence of KLF6 mutations is by no means ubiquitous in human cancer. We agree that sequencing artifacts secondary to tissue preservation are an important concern, which is why we have always used similarly prepared and stored paired normal tissue specimens as controls.4, 7, 8 Emerging KLF6 studies are now characterizing functions and features consistent with its role as a tumor suppressor, including interactions with cell cycle regulators,10 suppression of tumorigenicity in vivo,11 induction of proto-oncogene degradation,12 regulation of apoptosis,9 and promoter methylation and/or downregulation in cancer,9, 13 with reduced gene expression levels predicting disease outcome in both pulmonary adenocarcinoma14 and prostate cancer.15 Taken together, we believe these findings highlight the importance of continued independent studies using multiple sample sets to firmly clarify the role and mutation frequency of KLF6, or any candidate tumor suppressor, in both HCC and other human cancers. We welcome interest in this topic and look forward to its continued exploration. Sigal Kremer-Tal M.D.*, Helen Reeves M.D., Ph.D. , Goutham Narla B.S.*, John Martignetti M.D., Ph.D.*, Scott Friedman M.D.*, * Mount Sinai School of Medicine, New York, NY, University of Newcastle upon Tyne, United Kingdom.
Pulmonary vascular disease with congenital heart lesions: pathologic features and causes.
Authors: J IHoffman, A MRudolph, M AHeymann
Journal: Circulation (1981)

Pulmonary vascular disease, a serious complication of many congenital heart lesions, has three major components: increased muscularity of small pulmonary arteries; intimal hyperplasia, scarring and thrombosis; and reduced numbers of intraacinar arteries. The muscularity is due to increased stress on the vessel wall, and is reversible. The intimal changes may be due to endothelial damage, causing an imbalance between prostacyclin and thromboxane A2 production and leading to local platelet aggregation. This, in turn, may stimulate migration and division of myointimal cells, which thicken the intima and lead to scarring and thrombosis. Extensive intimal changes are probably irreversible, but the possibility of preventing them by use of agents that inhibit platelet aggregation needs to be considered. The mechanism of a decrease in numbers of intraacinar arteries is unexplained. The potential for growth of new vessels after corrective surgery of the cardiac defect is an important factor in restoring pulmonary ...
The effect of left ventricular systolic function on maximal aerobic exercise capacity in asymptomatic patients with coronary artery disease.
Authors: A AEhsani, DBiello, D RSeals, M BAustin, JSchultz
Journal: Circulation (1984)

The purpose of this study was to examine the relationship between maximal O2 uptake (VO2max) and left ventricular systolic function in patients with coronary artery disease. We studied 27 patients, age 50 +/- 10 years (mean +/- SD), who were asymptomatic and able to attain true VO2max. VO2max was defined by the leveling-off criterion and/or a respiratory exchange ratio of 1.15 or greater. Left ventricular ejection fraction was determined by gated cardiac blood pool imaging. In patients whose ejection fraction decreased with exercise, VO2max was 21 +/- 4 vs 27 +/- 4 ml/kg/min in those whose ejection fraction increased (p less than .001). Systolic blood pressure/end-systolic volume relation was shifted upward and to the right in the former group in response to peak exercise. In contrast, the pressure-volume relation was shifted upward and to the left in patients whose ejection fraction increased with exercise. Ejection fraction at rest did not correlate with VO2max. There was a significant but weak correlat...
Predictive accuracy of coronary artery calcification and abnormal exercise test for coronary artery disease in asymptomatic men.
Authors: R ALangou, E KHuang, M JKelley, L SCohen
Journal: Circulation (1980)

To determine the predictive accuracy of fluoroscopically detected coronary artery calcification (CAC) and a positive submaximal exercise test, 129 asymptomatic men were screened; 13 had both coronary artery calcification and positive exercise test (greater than or equal to 1.0 mm ST-segment depression). These 13 men were studied at coronary arteriography. They had a mean age of 44 years (range 41-56 years); none had history or symptoms of heat disease and all had normal resting ECGs at entry. CAC was detected in one artery in 10 men, in two arteries in two men, and in three arteries in one man. Coronary artery disease (CAD) was considered clinically significant if any major coronary branch was narrowed > 50%. Coronary arteriography revealed 12 men with clinically significant CAD (one-vessel CAD in four, two-vessel CAD in five and three-vessel CAD in three men) and one man with minor one-vessel CAD. The predictive accuracy was 100% for minor CAD and 92% for clinically significant CAD. The location of CAC a...
Telomere Shortening and Regenerative Capacity after Acute Kidney Injury
Authors: Lauren P. Wills, Rick G. Schnellmann
Journal: Journal of the American Society of Nephrology (2010)

With advances in modern medicine leading to improved health, the percentage of the population who are elderly is increasing. Associated with increasing age is a decline in renal function and loss of renal mass.1 These alterations in renal function predict increasing risk for mortality.2 The aging kidney also associates with multiple disease states, such as cardiovascular disease,3 cancer,4 and cognitive dysfunction,5 which increase susceptibility to ischemic acute kidney injury (AKI), from which the elderly are less likely to recover.6

Telomere attrition is implicated in many diseases associated with aging, including cardiovascular disease; however, an association between telomere shortening and decreased renal repair and regeneration after injury is largely unknown.7 The role of telomeres, repetitive DNA elements located at the end of chromosomes, is to prevent unwanted chromosome shortening and recombination. The length of telomeres is regulated by telomerase, which adds tandem TTAGGG repeats to the end of chromosomes to minimize shortening.8 Unfortunately, the majority of human cell types have limited telomerase activity, and, as we age, our telomeres shorten progressively with every cell division, eventually becoming critically short and resulting in senescence and apoptosis. This has serious implications for organ repair, regeneration, and recovery from injury.

In this issue of JASN , Westhoff et al. …
Acquired C1 Esterase Inhibitor Deficiency
Authors: Thomas Grünewald
Journal: Annals of Internal Medicine (2000)

Letters21 November 2000Acquired C1 Esterase Inhibitor DeficiencyThomas Grünewald, MDThomas Grünewald, MDKlinikum “St. Georg” Leipzig; D-04129 Leipzig, Germany (Grünewald)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-10-200011210-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Markovic and colleagues have written an excellent review on angioedema due to acquired C1 esterase inhibitor deficiency (1). However, from a practical standpoint, their proposal for diagnostic work-up in patients with angioedema of unknown cause is of concern: It is time-consuming and expensive to test three complement proteins before determinations of C1 esterase inhibitor activity in patients with suspected angioedema. In addition, C3 and C4 levels may be within normal limits during symptom-free intervals. Therefore, if the algorithm provided is used, some patients may be misdiagnosed. It seems more feasible to first determine C1 esterase inhibitor activity, ...Reference1. Markovic SN, Inwards DJ, Frigas EA, Phyliky RP. Acquired C1 esterase inhibitor deficiency. Ann Intern Med. 2000;132:144-50. LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Klinikum “St. Georg” Leipzig; D-04129 Leipzig, Germany (Grünewald) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAcquired C1 Esterase Inhibitor Deficiency Svetomir N. Markovic , David J. Inwards , Evangelos A. Frigas , and Robert P. Phyliky Acquired C1 Esterase Inhibitor Deficiency Marco Cicardi , Angelo Agostoni , and Alvin E. Davis III Acquired C1 Esterase Inhibitor Deficiency Allen P. Kaplan Acquired C1 Esterase Inhibitor Deficiency Antal Csepregi and Elemér Nemesánszky Acquired C1 Esterase Inhibitor Deficiency Svetomir N. Markovic , David J. Inwards , and Robert P. Phyliky Acquired C1 Esterase Inhibitor Deficiency Teresa Caballero , Maria Concepcion Lopez-Serrano , and Margarita Lopez-Trascasa Metrics Cited byHereditary angio-oedema in Denmark: a nationwide surveyProtease inhibitors in the treatment of hereditary angioedemaHereditary Angioedema as a Cause of Transient Abdominal Pain 21 November 2000Volume 133, Issue 10Page: 837KeywordsAlgorithmsEsterasesLaboratory testsOutpatientsProteinsResearch laboratories ePublished: 21 November 2000 Issue Published: 21 November 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Tips on… getting Ahead
Authors: Mark Griffiths
Journal: BMJ (2003)

You probably have many dreams and plans in your career or life, but how do you get there? There are no short cuts to reaching your goal, and it usually involves a lot of hard work and slog. Here are my top 10 tips for getting ahead.

Be realistic --Set achievable targets and don't expect too much too soon. It is much better …
Ectopic left atrial rhythm that produces QRS changes in absence of Wolff-Parkinson-White syndrome.
Authors: LZaman, NGarcia, R MLuceri, ACastellanos, R JMyerburg
Journal: Circulation (1983)

In an 18-year-old patient without manifest or concealed Wolff-Parkinson-White syndrome, spontaneous and paced left atrial impulses penetrated a left-sided AV nodal input and thereafter activated the ventricles in a normal fashion exclusively through the His-Purkinje system. On the other hand, sinus and paced right atrial impulses entered a right-sided atrioventricular nodal input that was completely dissociated from the left-sided input to subsequently activate the ventricles partly through Mahaim fibers and partly through the His-Purkinje system. The Mahaim fibers, which acted as bystanders during episodes of atrioventricular nodal reciprocating tachycardia, seemed to have extended from a distal, common (right-sided) intranodal pathway (or proximal His bundle) to the right ventricle or, although this is less likely, to the right bundle branch. More studies are necessary to determine whether the association on the surface electrocardiogram of an ectopic slow left atrial rhythm with changes in QRS mo...
Shall The Journal be Removed to Washington?
Authors: H. H. Darr
Journal: JAMA (1891)

<h3>To the Editor</h3> I am of the opinion that there is no good reason for movingThe Journaloffice. I think Chicago is the most suitable place for it. I vote for it to remain in Chicago, for that to be its permanent home. Caldwell, Texas, Jan. 30, 1891.
Facial vein of the rabbit. Intracellularly recorded hyperpolarization of smooth muscle cells induced by beta-adrenergic receptor stimulation.
Authors: J LPrehn, J ABevan
Journal: Circulation Research (1983)

A segment of the facial vein of the rabbit gains myogenic tone when placed under tension in a tissue bath (Winquist and Bevan, 1977); low frequency electrical stimulation of intramural nerves, or application of norepinephrine or isoproterenol produces relaxation, which is blocked by propranolol (1.0 microM). We measured membrane potential of single smooth muscle cells with microelectrodes during this beta-adrenergic receptor-mediated relaxation of the vein segment. Hyperpolarization (up to 30 mV) invariably accompanied relaxation. Average maximum resting potential recorded in normal Krebs solution was -46.8 +/- 3.6 mV (mean +/- SE); this increased to -70.8 +/- 3.0 mV when high concentrations (greater than 10 nM) of isoproterenol were added to the bath. Tone and membrane potential were very sensitive to intramural nerve stimulation. At 3-4 Hz, relaxation was about half maximal and hyperpolarization was 6-9 mV. The maximum hyperpolarization to nerve stimulation was 20-30 mV, about the same magnitude as that...
Accuracy of echocardiography in assessing left ventricular dimensions and volume.
Authors: D RBhatt, J BIsabel-Jones, G JVilloria, MNakazawa, S MYabek, R AMarks, J MJarmakani
Journal: Circulation (1978)

The accuracy of determining left ventricular function from echocardiography was assessed in 26 children (group I) with cineangiographically-determined normal left ventricular volume (LVV) and 28 children (group II) with large left ventricular volumes. Conventional LV echo dimensions were compared to the cineangiographic LV anterior-posterior minor axis (LVmA) and LVV. Very good correlations were found in group I between LV end-diastolic echo dimensions (LVEDD) and cine LVmA (r = 0.91) and between LVEDD and LV end-diastolic volume (LVEDV) by cine in group I (r = 0.86). In group II correlations were less accurate between LVEDD and diastolic LVmA and between LVEDD and LVEDV. There was poor correlation between the cine and echo percent of shortening (r = 0.41) and velocity of circumferential fiber shortening (VCF) (r = 0.51). This study demonstrates that M-mode echocardiography is a very useful method for determining LV dimensions in children with normal LV volume, but is less accurate in children with left v...
Increased ischemia-reperfusion injury to the heart associated with short-term, diet-induced hypercholesterolemia in rabbits.
Authors: R GTilton, P ACole, J DZions, ADaugherty, K BLarson, S PSutera, CKilo, J RWilliamson
Journal: Circulation Research (1987)

The effects of increased dietary cholesterol content on coronary vascular hemodynamics and endothelial cell transport function were assessed in isolated rabbit hearts during 3.5 hours of reperfusion after 30 minutes of global, no-flow ischemia. In control hearts from rabbits fed normal chow, perfusion pressure, left ventricular end-diastolic pressure, maximum +dP/dt, and the rate of intravascular clearance of radiolabelled albumin remained constant during 5 hours of continuous perfusion, while the mean transit time of radiolabelled albumin increased 1.6 X baseline. In ischemic hearts from rabbits fed normal chow, perfusion pressure increased 59% during reperfusion while left ventricular end-diastolic pressure and maximum +dP/dt returned toward control levels. The rate of intravascular clearance of radiolabelled albumin decreased 36%, and the mean transit time of albumin increased approximately 3 X baseline. Ischemia-reperfusion injury to the cardiac vasculature and musculature was markedly increased in he...
Transvenous defibrillation in humans via the coronary sinus.
Authors: G HBardy, M DAllen, RMehra, GJohnson, SFeldman, H LGreene, T DIvey
Journal: Circulation (1990)

A consistently effective transvenous defibrillation system for use in automatic defibrillators could significantly alter the approach to patients at risk of sudden death. Transvenous defibrillation systems that use a right ventricular (RV) electrode only or an RV electrode in combination with a chest patch are relatively inefficient at applying current to the posterolateral left ventricle. An RV electrode combined with a coronary sinus (CS) electrode, however, may improve current distribution to the posterolateral left ventricle. The purpose of this investigation, therefore, was to evaluate the effectiveness and safety of a specially designed transvenous lead system with a CS electrode capable of current delivery to this relatively inaccessible region of the heart. In 20 survivors of cardiac arrest, we determined defibrillation efficacy immediately before defibrillator surgery for monophasic pulses delivered between an RV catheter electrode and a CS catheter electrode system and compared these findings wi...
Osgood-Schlatter disease
Authors: R. Weiler, M. Ingram, R. Wolman
Journal: BMJ (2011)

In 1903, Osgood and Schlatter separately described a painful overuse condition affecting the tibial tuberosity. Osgood-Schlatter disease is a common cause of knee pain in children, associated with growth spurts, peaking in boys at about 12 to 15 years and girls at about 10 to 12 years. It is more common in boys than girls and up to 30% of children present with bilateral symptoms. Cadaveric and radiological studies have led to the theory that Osgood-Schlatter disease may be caused by forceful contractions of the quadriceps muscles at the proximal tibial apophysis insertion leading to multiple small avulsion fractures. This may lead to a firm enlargement of the tibial tubercle over time. The age of onset may be caused by the relative imbalance of strengthening quadriceps muscles compared with the growing bone. It is also associated with a shortened biceps femoris hamstring. Diagnosis is clinical and based on history and examination. Patients usually present with a gradual onset of pain localising at the tibial tuberosity, relieved by rest and aggravated by exercise, especially sports involving running and jumping. Patients can be reassured that the syndrome can be effectively self managed, but will often not fully resolve until the end of the growth spurt. However, up to 10% of patients experience persistent symptoms into adulthood, despite conservative measures.
Prostaglandins contribute to cardiovascular reflexes evoked by static muscular contraction.
Authors: C LStebbins, YMaruoka, J CLonghurst
Journal: Circulation Research (1986)

The purpose of this study was to determine the contribution of prostaglandins to the reflex cardiovascular responses induced by static contraction of the hind limb in cats, i.e., the exercise reflex. To accomplish this, the cardiovascular responses to hind limb contraction induced by electrical stimulation of spinal cord ventral roots L6-7 and S1 were compared before and after inhibition of prostaglandin synthesis (indomethacin, 2-6 mg/kg i.v., n = 5, or sodium meclofenamate, 2-6 mg/kg i.v., n = 5) or after injection of prostaglandin E2 into the hind limb arterial blood supply. Treatment with indomethacin attenuated the contraction-induced increase in mean arterial pressure and left ventricular dP/dt by 76% and 86%, respectively. Heart rate and average developed triceps surae muscle tension were unchanged. After administering sodium meclofenamate, the reflex response was attenuated to a similar degree. In the indomethacin-treated animals, injection of exogenous prostaglandin E2 (PGE2) partially restored t...
Fludarabine Melphalan Conditioning Followed By T-Replete Haplo Identical (Haplo) Transplantation or Haplo Cord (HC) Transplantation
Authors: Koen Van Besien, Andrew Artz, Richard E Champlin, Danielle Guarneri, Michael R. Bishop, Julianne Chen, Tsiporah B. Shore, Hongtao Liu, Gabriela Rondon, Sebastian A. Mayer, Stefan O. Ciurea
Journal: Blood (2017)
Receptor mechanisms in the human epicardial coronary artery. Heterogeneous pharmacological response to histamine and carbachol.
Authors: RGinsburg, M RBristow, KDavis
Journal: Circulation Research (1984)

We studied isolated ring segments from a number of sites along the course of epicardial coronary arteries from 24 human hearts in order to characterize regional responsiveness to vasoactive agents. Concentration-response curves revealed heightened sensitivity to histamine in the proximal portion of the coronary arteries, and increased sensitivity to carbachol in the distal portion of these same vessels. In contrast, the response to stimulation by calcium or phenylephrine was uniform throughout the length of the vessels examined. These data suggest that regional variations in agonist response reflect heterogeneity in receptor populations along the course of the human epicardial coronary artery.