tbuckley/cabot-search huggingface dataset:
Letter by Monfredi et al Regarding Article, “Physical Activity and Heart Rate Variability in Older Adults: The Cardiovascular Health Study”
Authors: Oliver Monfredi, Henggui Zhang, Mark R. Boyett
Journal: Circulation (2015)

Circulation recently published the work of Soares-Miranda et al, 1 in which physical activity and heart rate variability (HRV) in older adults were evaluated.The authors showed that greater leisure activity, walking distance, and walking pace are associated with higher HRV, which they interpreted as better autonomic function.We have reservations concerning this conclusion.4][5] We argue that HRV is a nonlinear surrogate of HR. 3 Soares-Miranda et al recognized the dependence of HRV on HR, and stated that HR was evaluated as a "potential confounder or mediator" of HRV in a separate analysis by "adding a multiplicative interaction term and assessing the statistical significance of the Wald test". 1 They state: "Results were…not appreciably altered" by "further adjustment for baseline HR". 1 However, they do not give the mean HRs of the different groups at different time points.Furthermore, there are no details of how HRV was corrected for differences in HR; we assume they made a linear correction, which will be inadequate to correct for the nonlinear dependence of HRV on HR. 3 The importance of HR on observed changes in HRV can be estimated: Zaza et al 4 have independently shown that the natural log of standard deviation of normal-to-normal beats-log n (SDNN)-changes by 0.16 to 0.17 for every 10 beats per minute (bpm) change in HR; our own data yield a similar value. 3It follows that the ratio of SDNN in 2 different conditions is an exponential function of the difference in
Abstract C55: Involvement of oxidative stress in the antitumor effect of mTOR inhibitors in mantle cell lymphoma
Authors: Heather L. Tardif, Margaret E. Tome, Margaret M. Briehl
Journal: Cancer Research (2009)

Abstract Existing treatments for mantle cell lymphoma (MCL) are non-curative, demonstrating a need for a refined treatment approach. MCLs are aggressive lymphomas, usually characterized by over-expression of cyclin D1. Recent clinical trials have shown promising results with the use of mammalian target of rapamycin (mTOR) inhibitors. While cyclin D1 can be regulated through the mTOR pathway, treatment with mTOR inhibitors often inhibit MCL growth without altering cyclin D1. Thus, the anti-tumor activity of mTOR inhibitors is likely mediated through other key targets. One potential target is C/EBPβ-LIP, a transcription factor regulated through the mTOR pathway. One target of C/EBPβ gene regulation is manganese superoxide dismutase (MnSOD), an antioxidant defense enzyme with tumor suppressor activity in some cell types. MnSOD catalyzes the dismutation of superoxide to hydrogen peroxide. Thus, it removes one form of reactive oxygen species (ROS) while generating another. Previous studies in our laboratory have shown that C/EBPβ-LIP levels decrease with mTOR inhibitor treatment in proportion to increasing MnSOD levels. We hypothesize that the anti-tumor effect of mTOR inhibitors in MCL is mediated by the increase in MnSOD protein expression and accumulation of ROS, specifically hydrogen peroxide. Here we investigated the effect of rapamycin on MnSOD and the levels of ROS in two human MCL-derived cell lines. High MnSOD levels correlated with increased sensitivity of cells treated with rapamycin. To investigate the biological effects of increased MnSOD expression, we measured overall ROS levels (DCFH) and the rate of hydrogen peroxide efflux with the fluorescent probe Amplex Red, which is indicative of changes to hydrogen peroxide levels in the cells. These results showed that both overall ROS and hydrogen peroxide levels increased in parallel with MnSOD expression. These increases in hydrogen peroxide were not due to decreased levels of catalase or glutathione peroxidase. Treatment with the general ROS scavenger, N-acetyl cysteine, reduced overall ROS, cellular levels of hydrogen peroxide, and the growth inhibitory effect of rapamycin. These findings indicate that rapamycin-induced cytostatic effect is characterized by generation of ROS, specifically hydrogen peroxide. This is likely due to the increased levels of MnSOD. By understanding the key signaling molecules in the anti-proliferative effects of rapamycin, we may be able to identify additional predictive markers to improve the therapeutic value of mTOR inhibitors, or study drug combinations that will enhance the effect of ROS-induced cytotoxicity. Citation Information: Cancer Res 2009;69(23 Suppl):C55.
Identification of Spermine as an Inhibitor of Erythropoiesis in Patients with Chronic Renal Failure
Authors: Heinz W. Radtke, Arvind B. Rege, Max B. Lamarche, Dagmar Bartos, Frantisek Bartos, Robert A. Campbell, James W. Fisher
Journal: Journal of Clinical Investigation (1981)

Fetal mouse liver and normal human bone marrow cell cultures were used for studies on the inhibition of erythroid colony formation (CFU-E) by sera from anemic patients with end-stage renal failure and the polyamine spermine. Sera from each of eight predialysis uremic anemic patients with end-stage renal failure produced a significant (P < 0.001) inhibition of erythroid colony formation in the fetal mouse liver cell cultures when compared to sera from normal human volunteers. In vivo or in vitro dialysis of the uremic sera with a 3,500-dalton exclusion limit membrane removed the inhibitor from uremic sera. The uremic serum dialysate provided by the membrane fractionation was significantly inhibitory in the erythroid cell cultures. When this dialysate was applied to gel filtration chromatography (Bio-Gel P-2) the inhibitor was found to be in the same molecular weight range as [(14)C]spermine. The polyamine spermine produced a dose-related inhibition of erythroid colony formation (CFU-E) in fetal mouse liver and normal human bone marrow cultures. Thus, the following evidence is provided that the in vitro inhibitor of erythropoiesis found in chronic renal failure patients' sera is identical with the polyamine spermine: (a) the inhibitor and radiolabeled spermine appeared in identical Bio-Gel P-2 effluent fractions; (b) when spermine was added to normal human sera at concentrations reported in sera of uremic patients, and studied in both the fetal mouse liver cell culture and normal human bone marrow cultures, a dose-related inhibition of erythroid colony (CFU-E) formation was noted; and (c) the inhibitory effects of crude uremic serum, uremic serum dialysate, and fractions of uremic serum dialysate from a Bio-Gel column, on erythroid colony formation were completely abolished by the addition of a specific rabbit antiserum to spermine.
A Tradition of Testing Ironclad Practices
Authors: Paul S. Swerdlow
Journal: JAMA (1992)

The therapeutic use of iron in medicine goes back nearly as far as recorded medicine itself. In 1500 BC, the Egyptians used iron therapeutically.<sup>1</sup>The ancient Hindu medicine Lauha Bhasma is essentially an iron preparation.<sup>2</sup>Cycles of iron use in excessive, ineffective, and appropriate doses have come and gone in medical practice. Indeed, current iron therapy has its relatively recent roots in the initial ferrokinetic studies performed in the middle of this century.<sup>3-6</sup>Now Zauber et al in this issue ofTHE Journal<sup>7</sup>have improved our understanding a bit more. Their article is important for two reasons: first, they have shown that iron supplementation is not always necessary after surgery involving significant blood loss; and second, they have questioned and studied a commonly accepted medical practice and found it to be unsubstantiated. See also p 525. Their study took advantage of the fact that their surgical
The Clinical Spectrum of Obesity
Authors: J. H. Sheldon
Journal: BMJ (1953)

My contribution to this discussion is an attempt to survey the clinical field of obesity in the light of recent knowledge. The underlying point of view is that appetite plays the fundamental part and that, although endocrine factors are capable of causing changes in weight based on internal rearrangements of protein and fat, the usual reason for gain of weight is an excess of calorie intake over expenditure.
Studies of the Central and Peripheral Hemodynamic Effects of Amyl Nitrite in Patients with Aortic Insufficiency
Authors: WOLFRAM DELIUS, EBBA ENGHOFF
Journal: Circulation (1970)

The cardiovascular reaction induced by amyl nitrite was studied in a main group of 11 patients with pronounced and isolated aortic insufficiency, and in an additional and more heterogeneous group of seven patients with moderate aortic insufficiency combined with other lesions, by measuring left ventricular end-diastolic pressure, systemic and peripheral arterial pressures, cardiac output, peripheral blood flow, and venous tone. Total peripheral resistance decreased, but local vascular resistance differed significantly between the upper and the lower extremities. In most cases arterial dilatation in the forearm (mainly muscle) was found. Simultaneously, there was uniform vasoconstriction in the calf (mainly muscle) which was interpreted to be secondary (baroreceptor reflex). This regional difference in circulatory reaction was also manifested in a pronounced change of the contour of the brachial arterial pulse, while the femoral arterial pulse was practically unchanged. The hand blood flow (skin) decreased while the foot blood flow did not change significantly. A marked fall in systemic arterial pressure and in left ventricular end-diastolic pressure was clearly demonstrated, and secondarily there was a rise in heart rate as well as a pronounced venoconstriction in both the upper and lower extremities, also interpreted to be secondary (a baroreceptor reflex). There was good correlation between maximal increase in heart rate and maximal increase in venous tone and also between the augmentation in heart rate and cardiac output. An elevation in stroke volume was noted in most cases. The reaction to amyl nitrite was not significantly different in the two groups of patients.
Prolonging What? Ethical Issues in Terminal Care
Authors: Jeremiah A. Barondess
Journal: JAMA (1983)

The emergence of the "living will" and its growth into a widespread movement (more than 5 million have been distributed since 1967 [Concern for Dying, an Educational Council, oral communication, December 1982]) are manifestations of multiple medical and social forces converging on the process of dying. The most prominent of these is the capacity of modern biomedical technology to prolong key physiological functions, often for long periods, in persons in comatose or vegetative states, regardless of ultimate prognosis. There has been increasing public awareness of this technological power and also of its potential impact, both emotional and financial, on the patient and his family. Just as physicians have been forced to reformulate the criteria permitting death to be diagnosed under these circumstances, now focusing on the viability of the brain,<sup>1</sup>many current and potential patients have begun to consider new and broader definitions of life, chiefly in terms of
Antipsychotic Use in the Medically Ill
Authors: Paul A. Silver, George M. Simpson
Journal: Psychotherapy and Psychosomatics (1988)

Antipsychotics are of use in a variety of medical settings. They can be used to treat organic mental disorders resulting from the medical illness and its therapy, as well as to control the symptoms of coexisting psychiatric conditions. Antipsychotics also have a variety of nonpsychiatric applications. This paper will review these uses of antipsychotic agents and how their administration must be modified in the medically ill.
Remarks on Myalgia: With Cases
Authors: T. Inman
Journal: BMJ (1858)

by trephininig it was found.In all these cases, however, there w-as the local inj'ury as a guide in the operation, and it is only in the very rare instances, where there is no distinct spot in- jure(l, no scalp-wound or fracture, that much hesitation need be felt on this point.The course of the symptoms, the time at which they occur, and the precedence of rigors and other indications of suippuration, sufficiently distinguish between efftisions of pus and those of blood or serurn, and a fortiori do the symptoms difler widely from those of morbid growths.
Vasculitis in a fixed drug eruption due to paracetamol
Authors: A. HARRIS, S.M. BURGE
Journal: British Journal of Dermatology (2006)

A 48‐year‐old man presented with a history of recurrent erylhematous lesions on the trunk and limbs. Examination suggested a fixed drug eruption and this was confirmed by oral challenge with paracetamol. The histology was unusual as it showed a teucocytoclastic vasculitis. Patients may have difficulty avoiding the offending drug because many drugs bought over the counter have similar names but different constituents. In addition, it may be difficult lo persuade the patient that a specific drug is responsible for their skin problem.
Enteral feeds may antagonise warfarin.
Authors: A J Watson, M Pegg, J R Green
Journal: BMJ (1984)

It is well known that a wide range of drugs can antagonise oral anticoagulants.Nevertheless, despite several reports from the United States' 3 and Australia4 it is not widely realised in Britain that enteral feeds may have an unexpectedly high content of vitamin K, which may cause apparent resistance to oral anticoagulants.We have recently seen such a case. Case reportA 49 year old white man had undergone a resection of the small bowel after a thrombosis in the mesenteric vein.He had a long past history of both superficial and deep venous thrombosis with pul- monary emboli.He had a family history of repeated venous thrombosis, but investigation showed no deficiency of antithrombin III.He was therefore being anticoagulated with warfarin at a stable main- tenance dose of 8 mg daily to maintain his prothrombin ratio within the range 2 0-3-3.Two months after starting warfarin he was given supplemental enteral nutrition because of increasing intolerance of normal food with symptoms of subacute small bowel obstruction.After starting Isocal 3550 ml daily his symptoms settled, but it proved necessary to increase the maintenance dose of warfarin to 13 mg over five days to maintain adequate anticoagulation.After six weeks of enteral feeding a further limited small bowel resection was per- formed.Subsequently he was able to return to a normal diet and Isocal was stopped.His daily warfarin requirement slowly fell to the original maintenance dose of 8 mg.When last seen he was in good health.
TCT-123 Initial Experience of Chimney Technique in Case of Aortic Arch Pathologies Involving the Supra-Aortic Branches
Authors: Renat Akchurin, Timur Imaev, Alexey Komlev, Peter Lepilin, Midat Osmanov, Alexander Kolegaev, Ilya Pokidkin
Journal: Journal of the American College of Cardiology (2012)
Diffusion of residual monomer in polymer resins.
Authors: W T Piver
Journal: Environmental Health Perspectives (1976)

A simplified mathematical model which made use of Fick's laws of diffusion written in spherical coordinates was developed to describe the rate of diffusion of residual monomers from polymer resins. The properties of the monomer-polymer system which influenced the amount of monomer remaining in the polymer as a function of time were the diffusivity and solubility of the monomer in the polymer, and the particle size of the polymer resin. This model was used to analyze literature data on the diffusion of residual vinyl chloride monomer in polyvinyl chloride resins made by the suspension process. It was concluded that particle size of the resin was a significant parameter which should be taken advantage of in process equipment designed to remove residual monomer from PVC resins. The diffusivity of the monomer in the polymer was a function of the solubility of the monomer in the polymer. Monomer solubility can be determined from Henry's law. It was suggested that this model could be adapted to describe diffusion of monomers from any monomer-polymer system, and would be a useful approach to modeling the transport of nonreactive chemical additives from plastics.
Urokinase-Type Plasminogen Activator Plays a Critical Role in Angiotensin II–Induced Abdominal Aortic Aneurysm
Authors: Gary G. Deng, Baby Martin-McNulty, Drew A. Sukovich, Ana Freay, Meredith Halks-Miller, Therese Thinnes, David J. Loskutoff, Peter Carmeliet, William P. Dole, Yi-Xin Wang
Journal: Circulation Research (2003)

We have previously demonstrated that urokinase-type plasminogen activator (uPA) is highly expressed in the aneurysmal segment of the abdominal aorta (AAA) in apolipoprotein E-deficient (apoE-/-) mice treated with angiotensin II (Ang II). In the present study, we tested the hypothesis that uPA is essential for AAA formation in this model. An osmotic minipump containing Ang II (1.44 mg/kg per day) was implanted subcutaneously into 7- to 11-month-old male mice for 1 month. Ang II induced AAA in 9 (90%) of 10 hyperlipidemic mice deficient in apoE (apoE-/-/uPA+/+ mice) but in only 2 (22%) of 9 mice deficient in both apoE and uPA (apoE-/-/uPA-/- mice) (P<0.05). Although the expansion of the suprarenal aorta was significantly less in apoE-/-/uPA-/- mice than in apoE-/-/uPA+/+ mice, the aortic diameters of the aorta immediately above or below the suprarenal aorta were similar between the 2 groups. Ang II induced AAA in 7 (39%) of 18 strain-matched wild-type C57 black/6J control mice. The incidence was significantly higher in atherosclerotic apoE-deficient (apoE-/-) mice, in which 8 (100%) of 8 mice developed AAA. Only 1 (4%) of 27 uPA-/- mice developed AAA after Ang II treatment. We conclude the following: (1) uPA plays an essential role in Ang II-induced AAA in mice with or without preexisting hyperlipidemia and atherosclerosis; (2) uPA deficiency does not affect the diameter of the nonaneurysmal portion of the aorta; and (3) atherosclerosis and/or hyperlipidemia promotes but is not essential for Ang II-induced AAA formation in this model.
GONORRHEAL CONJUNCTIVITIS; ITS TREATMENT.
Authors: LOUIS J. LAUTENBACH
Journal: JAMA (1896)

Conjunctival diseases are among the most frequent of eye affections, but each year as the general practitioner's special knowledge increases, he undertakes more and more the treatment of the inflammatory eye affections, especially of the appendices of the eye, and, in consequence, the specialist sees less and less of these troubles, except when present in an aggravated form. The study of conjunctival diseases is not only important in relation to their treatment but as they are very often symptomatic of other local or general conditions it is especially necessary to have a most intimate knowledge of their various aspects. Again their seriousness is not so much<i>per se</i>as in a weakening of the surrounding structures, thus giving rise to secondary inflammatory conditions. Of these conjunctival inflammations there are several which are specific or general in their origin, bearing a marked resemblance to each other which can be traced not
Radionuclide measurement of left ventricular volume: comparison of geometric and counts-based methods.
Authors: B M Massie, B L Kramer, E W Gertz, S G Henderson
Journal: Circulation (1982)

Radionuclide measurements of left ventricular volume were determined in 20 patients by geometric and nongeometric, counts-based techniques using data from first-pass and equilibrium blood pool scintigraphy. Two geometric analytic approaches were used: directly measured long and short axes and the area-length method. Each approach was applied to the single-plane right anterior oblique images obtained by the first-pass technique and to biplane data, using the right anterior oblique first-pass and left anterior oblique blood pool data together. For the nongeometric determinations, background-corrected left ventricular counts were related to blood counts. This ratio was converted to volume by means of a linear regression relationship with angiographic volumes. All methods yielded high correlation coefficients (r greater than or equal to 0.93), but the standard errors of the estimates for the geometric techniques were high, and therefore the 95% confidence limits were wide. The use of biplane data improved the correlations, but area-length analysis of digitized data was no better than direct measurement of short axes from the analog images. The counts-based, nongeometric method provided the highest correlation and lowest standard error. These findings indicate that nongeometric left ventricular volume measurements using equilibrium blood pool scintigrams are the most accurate radionuclide technique. This approach also permits multiple determinations with a single dose of radiotracer.
To all doctors in Britain
Authors: J. O. Drife
Journal: BMJ (1996)

Dear Doctor, You may be aware of articles in a Sunday newspaper alleging that doctors in some countries of the European Community continue to practise after they have died. The paper suggests that in parts of Europe posthumous practice is a common way of exploiting tax loopholes. Indeed, it claims to have found group practices in which only one of the names outside the surgery belonged to a living doctor.

Following these articles, the General Medical Council received letters from patients' organisations and members of parliament asking what measures are in place to ensure that this does not happen here.

The Council has been …
Reforming the consultant contract again?: Surgeons' fees for items of service would not work
Authors: Ewen F Flint
Journal: BMJ (2004)

Editor—What would happen to my fees if the patient failed to come in for surgery, or was sent home because of lack of beds, or my theatre list was cancelled because of staff shortages? Who would get the fee if a case was operated on by a trainee “flying solo” while the consultant sat at the back of theatre?

There are too many anomalies to even consider paying consultants in the way outlined by Maynard and Bloor.1
South Africa: Research Worker's Paradise
Authors: R. HOFFENBERG
Journal: Annals of Internal Medicine (1975)

Comments and Corrections1 September 1975South Africa: Research Worker's ParadiseR. HOFFENBERG, M.D., PH.D., F.R.C.P.R. HOFFENBERG, M.D., PH.D., F.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-3-428_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I found the article "South Africa: Research Worker's Paradise" (Ann Intern Med82:588, 1975) unusually offensive. I did not like its overall tone and its rather ghoulish suggestion that investigators should hurry before it is too late to seize the opportunities for research provided there by the manifest suffering of the majority of its black population. Nor did I like the way in which Dr. Gilder carefully avoided all reference to the root political causes of the patterns of ill health he so enthusiastically proposes to exploit. His explanations range from the naive to the obscure, and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: R. HOFFENBERG, M.D., PH.D., F.R.C.P.Affiliations: Department of Medicine Queen Elizabeth Hospital, Edgbaston Birmingham B15 2TH, England PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCatalysis and Related Reactions with Compounds Containing Heteronuclear Metal Metal Bonds 1 September 1975Volume 83, Issue 3Page: 428-428 ePublished: 1 December 2008 Issue Published: 1 September 1975 PDF downloadLoading ...