tbuckley/cabot-search huggingface dataset:
The pressure-flow response of the pulmonary circulation in patients with heart failure and pulmonary vascular disease.
Authors: J S Janicki, K T Weber, M J Likoff, A P Fishman
Journal: Circulation (1985)

Although it is well known that the pulmonary circulation is altered in patients with pulmonary arterial or venous hypertension, the resultant hemodynamic behavior has not been systematically studied. We undertook to do so in a group of patients with pulmonary hypertension of diverse etiology. We measured pulmonary arterial (PAP) and occlusive wedge pressures and cardiac output at rest (i.e., standing) and during progressive upright treadmill exercise in 51 patients. Forty-two had chronic, stable, cardiac failure secondary to ischemic, myopathic or valvular heart disease and were grouped according to whether their mean PAP was less than (normotensive) or greater than (hypertensive) 19 mm Hg, and nine had pulmonary vascular disease of diverse etiology and were considered separately. In the majority of patients, we found that irrespective of whether the hypertension was arterial or venous in origin or etiology: the mean PAP-flow relationship was linear; pulmonary capillary wedge pressure was greater than or equal to the average closure pressure of the pulmonary vascular bed and could therefore be used as the downstream pressure in calculating pulmonary vascular resistance; and pulmonary vascular resistance declined with exercise. Notable exceptions to the third observation were patients with valvular heart disease or a resting pulmonary vascular resistance greater than 800 dyne-sec-cm-5.
Pneumococcus Vaccine and Diabetes-Reply
Authors: James M. Moss
Journal: JAMA (1981)

<h3>In Reply.—</h3> I am heartily in favor of any program that will decrease morbidity and mortality in patients with diabetes mellitus. I am vigorously opposed to any program that discriminates either for or against diabetics when there is no evidence that such discrimination is justified or to the benefit of the patient. The assumption that diabetics have decreased resistance to infection is based on studies performed in patients with a complicated or poorly controlled condition. There is no evidence that this is true for the vast majority of patients with diabetes. Pneumococcus vaccine is not cost-effective for the general population, and there is no evidence that it is cost-effective for patients with diabetes. Therefore, diabetes mellitus is not a justified indication for use of this vaccine.
STUDIES ON ARTIFICIAL ANTIGENS
Authors: Bernard B. Levine, Antonio Ojeda, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1963)

The genetic transmission of the capacity to develop an immune response to hapten-polylysine conjugates was studied in guinea pigs. 82 per cent of the 22 offspring of 8 pairs of responder (guinea pigs which are capable of an immune response) parents were also responders, whereas, none of the 26 offspring of 9 pairs of non-responder parents were responders. None of 11 strain 13 guinea pigs and 100 per cent of 40 strain 2 guinea pigs were responders. These findings are consistent with the view that the capacity to respond immunologically to hapten-polylysine conjugates is genetically transmitted as a unigenic Mendelian dominant.
Cyclophosphamide Therapy in the Nephrotic Syndrome in Childhood
Authors: M. W. Moncrieff, R. H. R. White, C. S. Ogg, J. S. Cameron
Journal: BMJ (1969)

Forty-six children with the nephrotic syndrome whose renal biopsy specimens showed minimal changes and whose response to corticosteroid therapy was unsatisfactory were treated with cyclophosphamide. Three patients were completely steroid-resistant from the outset and the remainder were steroid-dependent. In several patients steroids controlled the condition less effectively with time. Most patients showed signs of steroid toxicity, and growth retardation was striking.A moderate leucopenia was induced with cyclophosphamide, and treatment was maintained for three to four months in the majority of cases. Thirty-eight children (83%) have remained in complete remission off all treatment for periods of 3 to 23 months, 33 after one course of cyclophosphamide and five after a second course. Two other patients who remitted but relapsed later are still on treatment. In only six patients was full remission not obtained, and three of these were steroid-resistant from the start. Two died from pneumonia and adrenal failure and four continued to have proteinuria, though in one an impressive reduction occurred.The results indicate that cyclophosphamide therapy is an effective alternative for nephrotic children with normal glomeruli on light microscopy who develop steroid dependence or resistance, and who exhibit toxic effects of steroid therapy.
710 EVOLUTION OF GLOMERULAR FILTRATION RATE IN HIV-INFECTED, HIV-HBV COINFECTED AND HBV-INFECTED PATIENTS RECEIVING TENOFOVIR
Authors: L. Cotte, M.-A. Le Pogam, J.-B. Okon, P. Trolliet, C. Brochier, M. Maynard, F. Bailly, P. Miailhes, F. Zoulim
Journal: Journal of Hepatology (2011)
Amantadine in the Treatment of Parkinsonism And Related Diseases
Authors: Robert L. Weinmann
Journal: JAMA (1973)

<h3>To the Editor.—</h3> "Drug Therapy of Parkinsonism" by Yahr and Duvoisin<sup>1</sup>and the subsequent discussion of "Treatment of Parkinsonism" by Young<sup>2</sup>illustrate some of the chemotherapeutic paradoxes indigenous to the treatment of this disease spectrum. Recognized for its predictive value relative to the subsequent use of levodopa (208:1168, 1969), the mechanism of action of amantadine is less understood than that of levodopa. Schwab et al estimate that amantadine "may function by decreasing inactivation of dopamine by blocking its presynaptic uptake and thereby prolonging its effective half-life following synaptic release" (222:792, 1972). Clinically, they also recognize that "the beneficial effect of amantadine occurs rapidly (within the first 24 hours) and usually follows the introduction of the first capsule." In our practice, amantadine has been used since 1969 and certain features are outstanding when the benefits and side effects of this drug are compared with levodopa. While confusion and disorientation
THE HISTOPATHOLOGY OF POMPHOLYX
Authors: RICHARD L. SUTTON
Journal: JAMA (1913)

Pompholyx was first described, as a form of dyshydrosis, by Tilbury Fox,<sup>1</sup>who was of the opinion that the condition was characterized essentially by "the retention in the follicles of the skin of sweat, rapidly and freely excreted," and believed that the affection bore the same relation to the sweat follicles that acne vulgaris does to the sebaceous glands. Hutchinson<sup>2</sup>who independently recognized and described the disease at about the same time, was opposed to this view, and, basing his argument on the symmetry and the spontaneous appearance and disappearance of the clinical manifestations, and on the fact that the condition was seen most frequently in persons whose vitality had been lowered by worry, overwork and similar agencies, concluded that it was an acute, inflammatory disease of the rete, neurotic in origin. He<sup>3</sup>suggested for it the name "cheiropompholyx."
Abstract 1673: A pharmacokinetics/pharmacodynamics evaluation of the concentration-QTc relationship of PF-02341066 (PF-1066), an ALK and c-MET/HGFR dual inhibitor administered orally to patients with advanced cancer
Authors: Dana Nickens, Weiwei Tan, Keith Wilner, D. Ross Camidge, Geoffrey Shapiro, Bruce Dezube, Jeffrey Clark
Journal: Cancer Research (2010)

Abstract Objective: Assess the potential effect of PF-1066 plasma concentrations on the observed RR corrected QT interval in patients with advanced cancer. Methods: Plasma concentrations of PF-1066 (total drug) and ECG data were collected in study A8081001, an open label, multi-center Phase 1 dose escalation, and safety, pharmacokinetic and exploratory study (J Clin Oncol 27:15s, 2009 (suppl; abstr 3509)). PF-1066 was administered orally on an empty stomach once (QD) or twice (BID) a day in continuous 28-day cycles with doses ranging from 50 mg QD to 300 mg BID. Time-matched, triplicate (≥ 2 minutes apart) ECGs were obtained during the screening period, at pre-dose, 6 hours (∼ Cmax), and 24 hours post-dose on Cycle 1 Day 1, and at pre-dose and 6 hours (∼ Cmax) post-dose on Cycle 1 Day 15 and Cycle 2 Day 1. Baseline ECG data was used to assess which heart rate correction method (QTcB, QTcF and a study specific correction, QTcS) was most appropriate. A linear mixed effects model was used to evaluate the relationship between plasma concentrations and the RR-interval and corrected QT-interval. Results: A total of 62 patients were available for this analysis. The majority of patients had at least 5 triplicate measurements post dose. Fifty-three percent (n=33) were male. Plasma concentrations ranged from 0.228 ng/mL to 1040 ng/mL and the median concentration over all doses was 83.2 ng/mL. At baseline, median heart rate, QTcB- and QTcF-interval were, respectively, 80 bpm, 429 msec and 408 msec. The post-treatment median heart rate, QTcB- and QTcF-interval were, respectively, 73 bpm, 432 msec and 416 msec. The concentration-RR analysis indicates that on average heart rate decreases at approximately 2.5 bpm per 100 ng/mL increase in PF-1066 concentration. QTcS was determined as the most appropriate heart rate correction method for QT-interval. The estimated slope for concentration-QTcS-interval is 0.0076 msec/ng/mL (90% conf. limits: −0.0051, 0203), indicating a small but not statistically significant positive trend in the concentration-QTcS relationship. Based on the model, the average drug associated increase in QTcS is 2.9 msec at the mean Cmax following 250 mg BID dosing. Conclusion: Based on the PK/PD analysis, a clinically relevant QT prolongation is not expected within the therapeutic dose range (up to 250 mg BID) of PF-1066 in patients with advanced cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1673.
Maximal Treadmill Stress Testing for Cardiovascular Evaluation
Authors: MYRVIN H. ELLESTAD, WILLIAM ALLEN, MAURICE C. K. WAN, GEORGE L. KEMP
Journal: Circulation (1969)

Experience with a maximal treadmill stress testing procedure which is relatively safe, simple, and reproducible is reported. It has been used in normal persons and cardiac patients with ages ranging from 7 to 83 years. There have been no deaths in our total experience of 4,028 maximal capacity stress tests. Maximal capacity is predicted by the patient's peak predicted pulse rate. Sixty-three per cent of those with ischemic S-T segments did not experience pain of any type.
Critical evaluation of three chest radiograph scores in cystic fibrosis.
Authors: S M Sawyer, J B Carlin, M DeCampo, G Bowes
Journal: Thorax (1994)

BACKGROUND--A number of chest radiographic scores have been developed to assess the severity of respiratory disease in cystic fibrosis but critical statistical evaluation has been limited. In particular, the chest radiograph component of the National Institutes of Health (NIH) clinical score has not previously been validated. Three different chest radiograph scores have been compared and the association between them and lung function tests investigated. METHODS--The interobserver and intraobserver variation of the Brasfield, NIH chest radiograph, and the Royal Children9s Hospital (RCH) chest radiograph score was assessed by three observers--a paediatric radiologist, a junior and a senior respiratory physician--who independently scored, on separate occasions, 62 chest radiographs randomly selected from three age strata of patients ranging from 7 to 18 years. Lung function tests were available for 61 patients obtained within three months of the chest radiograph. Two way analysis of variance was used to estimate components of variation in scores. RESULTS--Results were similar for the Brasfield and NIH scores, both of which demonstrated greater precision than the RCH score, but the estimated repeatability of the Brasfield and NIH scores can be expected to differ by up to 20% of the maximum score. The reliabilities (intraclass correlation) are all reasonably high at 0.74, 0.73, and 0.61 for the Brasfield, NIH, and RCH scores, respectively. The estimated correlation between radiographic scores and lung function tests, adjusted for attenuation caused by measurement error, showed a similar correlation for all three scoring methods ranging from 0.55 to 0.78. Correlations were slightly greater with FEV1% than FVC%. These correlations are substantial but not high, indicating that a large proportion of the variability in radiographic scores cannot be explained by lung function measurements. CONCLUSIONS--The Brasfield and NIH chest radiograph scores have very similar statistical profiles and can be equally recommended if a chest radiograph score is to be used. The RCH radiographic score appears to be less reliable. The limitations of these scores need to be understood.
Further Observations on Diagnosis and Management of General Practice Respiratory Illness using Simulated Patient Consultations
Authors: J. G. R. Howie
Journal: BMJ (1974)

Twenty general practitioners co-operated in a study of the decision-making process in general practice respiratory illness. Ten simulated standard-patient consultations were used, each being included twice, once to make a decision on diagnosis and once to make a decision on management.Comparison of simulated behaviour with previous studies of observed and self-recorded behaviour showed encouraging agreement. Examination of 200 pairs of management and treatment decisions showed that fewer pieces of information were required for a management than a diagnostic decision on 111 occasions; in 43 pairs the quantity required was the same for each decision. The exact information required to make a decision on diagnosis was included in the information required to decide management on only 30 (15%) of the 200 possible occasions.When disagreement was found over management of a simulated case a decision to prescribe an antibiotic required less information than a decision not to prescribe an antibiotic.
Alterations in G-protein-regulated transmembrane signalling induced in murine myocardium by coxsackievirus B3 infection
Authors: J. Novotny, P. Kvapil, F. Jelinek, L. A. Ransnas
Journal: Cardiovascular Research (1995)

Cardiomyopathy is usually associated with marked alterations in myocardial transmembrane signalling. Although acute viral myocarditis may result in chronic cardiomyopathy in some cases, the possible consequences of viral infection on function of the myocardial signal-transducing complex have not been explored. Therefore, the present study was designed to investigate the G-protein-regulated adenylyl cyclase signalling system in murine myocardium during myocarditis induced by coxsackievirus B3 (CVB3) infection.We examined the functional characteristics of adenylyl cyclase as well as the function and distribution of beta-adrenoceptors, m-cholinoceptors and G-proteins in myocardial plasma membranes isolated from the hearts of mice with acute (7 days pi) or late phase (21 days pi) myocarditis and the obtained results were compared with the corresponding data determined in age-matched controls.While the basal adenylyl cyclase activity was not significantly altered, the ability of forskolin, sodium fluoride and GTP gamma S to activate adenylyl cyclase was lowered by about 20% in samples from virus-infected animals. The level of Gs alpha in myocardial plasma membranes as well as the functional activity of Gs alpha was not affected by viral infection, but the Gi alpha content was increased by about 20%. The total number of beta-adrenoceptors in myocardial plasma membranes increased by about 12-15% due to higher content of the beta 2-adrenoceptor subtype. Although the agonist-binding parameters of beta-adrenoceptors were not significantly altered, the ability of these receptors to mediate stimulation of adenylate cyclase was markedly diminished (by 56-80%). The total number of m-cholinoceptors in samples derived from virus-infected mice increased considerably (by 29-59%) and a significant proportion of the receptors shifted to a higher affinity status, but their ability to transduce agonist signals was impaired.These data are the first to demonstrate that several different sites of the myocardial G-protein-regulated adenylyl cyclase signalling complex are significantly altered in acute as well as in late phase of CVB3-induced myocarditis.
Pediatricians Participating in Medicaid-Reply
Authors: Peter A. Margolis
Journal: JAMA (1992)

<h3>In Reply.</h3> —The data from Dr Fox and Mr Phua are of interest because they reflect the effects of actual increases in Medicaid payments on obstetricians' participation in Medicaid. Although the increase in payments stemmed declining participation rates, they found, as we did, that the overall effect of increased payments on participation was modest. The second North Carolina Pediatric Society survey points up how different approaches to measuring participation in Medicaid may yield different results. This survey differed somewhat from ours in that it was sent only to pediatricians who were members of the pediatric society, a different definition was used to determine if pediatricians were in active practice, the findings regarding the relationship of Medicaid payments to participation were not controlled for other factors that may influence physicians' decisions to participate in Medicaid, and the survey asked what physicians would do in response to increased payments rather than assessing
A NOTE ON RAT-BITE FEVER, WITH REPORT AND TEMPERATURE CHART OF A RECENT CASE
Authors: R. W. Cruickshank
Journal: BMJ (1912)

NAT-BITE FEVER.[MEDICAL JOURNA 'r437)oSSible, wlhich it is not, that each group receive an equal aimount of infection.Then if the same amount of infection were to equally infect tlle children in both grouips, it would follow that infcction must be the principal deter- imining cause of the disease.Again, if the samiie amount of infection whiclh infected the children of infectious cases did not infect the children of non-infectious cases, it is clear that this difference in susceptibility would be due to some factor other than transmitted qualities commuon to botlh, and other than the amount of infection wlhich we
VEGF: A modifier of the del22q11 (DiGeorge) syndrome?
Authors: Ingeborg Stalmans, Diether Lambrechts, Frederik De smet, Sandra Jansen, Jian Wang, Sunit Maity, Paige Kneer, Maren von der Ohe, Ann Swillen, Christa Maes, Marc Gewillig, Daniel G.M. Molin, Peter Hellings, Thurid Boetel, Maartin Haardt, Veerle Compernolle, Mieke Dewerchin, Stephane Plaisance, Robert Vlietinck, Beverly Emanuel, Adriana C. Gittenberger-de Groot, Peter Scambler, Bernice Morrow, Deborah A. Driscol, Lieve Moons, Camila V. Esguerra, Geert Carmeliet, Annett Behn-Krappa, Koen Devriendt, Désiré Collen, Simon J. Conway, Peter Carmeliet
Journal: Nature Medicine (2003)
Abstract B45: The short-term effects of arsenic on Cdk5-dependent apoptosis of prostate cancer cells
Authors: Mei-Chih Chen, Paulus S. Wang, Ho Lin
Journal: Clinical Cancer Research (2010)

Abstract Arsenic compounds have been used widely in medicine to treat a variety of diseases. However, it has also been believed to involve the carcinogenesis of prostate cancer and the hormone disruption might be one of the causes. Our previous results indicate that digoxin treatment leads to apoptosis of prostate cancer cells through Cdk5 overactivation, in which the regular activator of Cdk5, p35, is cleaved into more potent one, p25. Here, our latest data showed that arsenic also caused p35 cleavage and subsequently Cdk5 overactivation in prostate cancer cells. Similarly, this arsenic- induced stimulatory effect on Cdk5 resulted in apoptosis of prostate cancer cells accompanying with the degradation of androgen receptor in LNCaP cells. This result implies that androgen is no longer a trophic factor for prostate cancer cells after arsenic treatment. Although STAT3 was identified by us as a Cdk5 substrate responding to tumor growth, arsenic-triggered Cdk5 overactivation did not increase STAT3 phosphorylation. In conclusion, although long-term exposure of arsenic possibly causes prostate cancer, our present results provide evidence indicating that in vitro and short-term treatments of arsenic might lead to apoptosis of prostate cancer cell lines through Cdk5 overactivation pathway. This study may arouse the new indication for the old chemical and also shed light on the application on cancer therapy. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B45.
Triggering T cells by otherwise inert hybrid anti-CD3/antitumor antibodies requires encounter with the specific target cell.
Authors: E Roosnek, A Lanzavecchia
Journal: The Journal of Experimental Medicine (1989)

We used a purified bispecific antibody (Ab) against CD3 and an ovarian carcinoma (OVCA) antigen to ask whether the binding of a monovalent ligand to CD3 can induce triggering of T cells. In the presence of OVCA cells, this Ab bridges the CD3 complex to the target cell and triggers proliferation and cytotoxicity in T cells. In the absence of target cells, however, this monovalent Ab, even when bound to T cells at high levels, fails to induce any increase in cytosolic Ca2+, nor does it induce responsiveness to IL-2 or modulation of the CD3 complex. Because it is inert when bound monovalently, this hybrid Ab can be used to arm in vitro CTL clones, which then retain the capacity to kill the specific tumor for up to 2 d.
Mitochondrial dysfunction observed in situ in cardiomyocytes of rats in experimental diabetes
Authors: Y. Tanaka, N. Konno, K J Kako
Journal: Cardiovascular Research (1992)

Objective: The aim was to investigate effects of experimental diabetes and insulin treatment on heart myocytes, particularly on the mitochondrial function studied in situ in isolated cardiomyocytes. Methods: 20 male Sprague-Dawley rats (140-160 g) were made diabetic by intraperitoneal streptozotocin, 70 mg·kg−1. Ten then received daily subcutaneous injections of ultra lente insulin (starting dose of 3 units·d−1) for 7-15 d from the 20th day after streptozotocin. There was a control group of 11 rats. The rats were killed 21-35 d after the induction of diabetes, and heart myocytes were isolated by collagenase digestion. The 45[Ca]2+ uptake of mitochondria in situ in permeabilised myocytes, the transmembrane potential gradient of mitochondria, and the respiration of myocytes, as well as the cell yield and cell [45Ca]2+ uptake, were examined. Results: Mitochondrial uptake of [45Ca]2+ was significantly decreased in the diabetic group compared to control at cytosolic calcium concentrations between 760 nM and 44.6 μM. The mitochondrial potential of diabetic myocytes, estimated from the distribution of [3H]triphenylmefhylphosphonium+, was slightly but significantly decreased from the control value. Cell respiration, measured polarographically in the presence of pyruvate and malate or succinate as oxidisable substrates, and with or without 2,4-dinitrophenol, was decreased by diabetes. The rapidly exchangeable [45Ca]2+content in the myocyte with intact sarcolemmal membrane ("cell Ca2+ uptake") and the yield of cells from heart tissue were also diminished in diabetic rats. These changes were returned to normal by insulin treatment of 7 d or longer. Conclusions: Insulin deficiency at early stages causes defects of mitochondrial function detectable in situ in cardiomyocytes. This suggests the possibility that such alterations are causative factors in the development of diabetic cardiomyopathy.