tbuckley/cabot-search huggingface dataset:
Age related alteration in cholinergic but not adrenergic response of rat coronary vasculature
Authors: N. Su, N. Narayanan
Journal: Cardiovascular Research (1993)

Journal Article Age related alteration in cholinergic but not α adrenergic response of rat coronary vasculature Get access Na Su, Na Su Department of Physiology, Health Sciences Centre, University of Western Ontario, London, Ontario, Canada N6A 5C1: N Su, N Narayanan. Correspondence to Dr Narayanan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Njanoor Narayanan Njanoor Narayanan Department of Physiology, Health Sciences Centre, University of Western Ontario, London, Ontario, Canada N6A 5C1: N Su, N Narayanan. Correspondence to Dr Narayanan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 2, February 1993, Pages 284–290, https://doi.org/10.1093/cvr/27.2.284 Published: 01 February 1993 Article history Received: 16 March 1992 Accepted: 03 July 1992 Published: 01 February 1993
The relationship between six-month progression-free survival and 12-month overall survival end points for phase II trials in patients with glioblastoma multiforme
Authors: Karla V. Ballman, Jan C. Buckner, Paul D. Brown, Caterina Giannini, Patrick J. Flynn, Betsy R. LaPlant, Kurt A. Jaeckle
Journal: Neuro-Oncology (2006)

Common end points for phase II trials in patients with glioblastoma multiforme (GBM) are six-month progression-free survival (PFS6) and 12-month overall survival (OS12). OS12 can be accurately measured but may be confounded with subsequent therapies upon progression, whereas the converse is true for PFS6. Our goal was to assess the relationship between these end points separately for phase II trials in patients with newly diagnosed GBM and patients with recurrent GBM. Data were pooled from 11 North Central Cancer Treatment Group trials for patients with newly diagnosed GBM (n = 1348). All patients received radiotherapy and pharmaceutical therapy (before, during, or after radiotherapy). Data were pooled from 16 trials that used various pharmaceuticals in treating patients for recurrent GBM (n = 345). All trial regimens were declared nonefficacious by predefined criteria. Overall per-patient concordance was estimated with a kappa statistic. The relationship between OS12 and PFS6 across study arms was assessed by weighted linear regression and Pearson's correlation. Simulation was used to determine the agreement of study outcomes when using PFS6 versus OS12 end points. Cox models with progression status as a time-dependent variable and Kaplan-Meier estimators were used to ascertain the association between progression-free survival status and overall survival. At present, 97% of the patients with newly diagnosed GBM and 95% of those with recurrent GBM have died. The PFS6 and OS12 were 43% and 41%, respectively, for patients with newly diagnosed disease and 9% and 14% for patients with recurrent disease. There was only moderate concordance between the end points on both the patient level and the study level. For the simulation studies, we established phase II efficacy criteria for each end point by using the pooled estimates of OS12 (PFS6) as historical controls. The study decisions made using PFS6 and OS12 were in agreement 88% and 90% of the time for the trials of newly diagnosed and recurrent disease, respectively. Finally, there was a strong association between progression-free survival status and overall survival. PFS6 seems to be a reasonable end point for phase II trials in patients with recurrent glioblastoma.
Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis)
Authors: Immacolata Andolfo, Roberta Russo, Francesco Manna, Boris E. Shmukler, Antonella Gambale, Giuseppina Vitiello, Gianluca De Rosa, Carlo Brugnara, Seth L. Alper, L. Michael Snyder, Achille Iolascon
Journal: American Journal of Hematology (2015)

Dehydrated hereditary stomatocytosis (DHSt) is an autosomal dominant congenital hemolytic anemia with moderate splenomegaly and often compensated hemolysis. Affected red cells are characterized by a nonspecific cation leak of the red cell membrane, reflected in elevated sodium content, decreased potassium content, elevated MCHC and MCV, and decreased osmotic fragility. The majority of symptomatic DHSt cases reported to date have been associated with gain-of-function mutations in the mechanosensitive cation channel gene, PIEZO1. A recent study has identified two families with DHSt associated with a single mutation in the KCNN4 gene encoding the Gardos channel (KCa3.1), the erythroid Ca(2+) -sensitive K(+) channel of intermediate conductance, also expressed in many other cell types. We present here, in the second report of DHSt associated with KCNN4 mutations, two previously undiagnosed DHSt families. Family NA exhibited the same de novo missense mutation as that recently described, suggesting a hot spot codon for DHSt mutations. Family WO carried a novel, inherited missense mutation in the ion transport domain of the channel. The patients' mild hemolytic anemia did not improve post-splenectomy, but splenectomy led to no serious thromboembolic events. We further characterized the expression of KCNN4 in the mutated patients and during erythroid differentiation of CD34+ cells and K562 cells. We also analyzed KCNN4 expression during mouse embryonic development.
Factors influencing tackle injuries in rugby union football.
Authors: W M Garraway, A J Lee, D A Macleod, J W Telfer, I J Deary, G D Murray
Journal: British Journal of Sports Medicine (1999)

OBJECTIVES: To assess the influence of selected aspects of lifestyle, personality, and other player related factors on injuries in the tackle. To describe the detailed circumstances in which these tackles occurred. METHODS: A prospective case-control study was undertaken in which the tackling and tackled players ("the cases") involved in a tackle injury were each matched with "control" players who held the same respective playing positions in the opposing teams. A total of 964 rugby matches involving 71 senior clubs drawn from all districts of the Scottish Rugby Union (SRU) were observed by nominated linkmen who administered self report questionnaires to the players identified as cases and controls. Information on lifestyle habits, match preparation, training, and coaching experience was obtained. A validated battery of psychological tests assessed players' trait anger and responses to anger and hostility. The circumstances of the tackles in which injury occurred were recorded by experienced SRU coaching staff in interviews with involved players after the match. RESULTS: A total of 71 tackle injury episodes with correct matching of cases and controls were studied. The following player related factors did not contribute significantly to tackle injuries: alcohol consumption before the match, feeling "below par" through minor illness, the extent of match preparation, previous coaching, or practising tackling. Injured and non-injured players in the tackle did not differ in their disposition toward, or expression of, anger or hostility. Some 85% of tackling players who were injured were three quarters, and 52% of injuries occurred when the tackle came in behind the tackled player or within his peripheral vision. Either the tackling or tackled player was sprinting or running in all of these injury episodes. One third of injuries occurred in differential speed tackles--that is, when one player was travelling much faster than the other at impact. The player with the lower momentum was injured in 80% of these cases. Forceful or crunching tackles resulting in injury mostly occurred head on or within the tackled player's side vision. CONCLUSIONS: Attention should be focused on high speed tackles going in behind the tackled player's line of vision. Comparative information on the circumstances of the vast majority of tackles in which no injury occurs is required before any changes are considered to reduce injuries in the tackle.
Magnetic measurement of S-T and T-Q segment shifts in humans. Part I: Early repolarization and left bundle branch block.
Authors: P Savard, D Cohen, E Lepeschkin, B N Cuffin, J E Madias
Journal: Circulation Research (1983)

The direct-current magnetocardiogram not only shows the features usually seen on the electrocardiogram, but also shows the T-Q (baseline) shift due to cardiac injury current. The first direct-current magnetocardiogram measurements of the human heart are presented here. The hypothesis tested is that there is no injury current associated with the S-T shift seen in two electrocardiogram abnormalities: early repolarization, and left bundle branch block. The data from three typical early repolarization subjects and one typical left bundle branch block patient are presented. It is found, in each case, that although there is appreciable S-T shift, there is essentially no baseline shift on the direct-current magnetocardiogram. The absence of baseline shift proves that the S-T shifts in these cases are not "apparent" shifts, caused by a dc injury current which is interrupted during the S-T interval; instead, these are "true" S-T shifts caused by a current flowing only during systole, presumably due to an altered repolarization of the ventricles. It is also found that the direct-current magnetocardiogram does not have routine clinical application because of a practical problem. This is the presence of false baseline shifts due to noncardiac currents, mostly in the gastrointestinal tract, which could be suppressed in only about one-third of the subjects. However, the direct-current magnetocardiogram may be useful as a research tool, for clarifying the cause of the S-T shift in selected subjects.
TNF therapy in psoriatic arthritis and psoriasis
Authors: P Mease
Journal: Annals of the Rheumatic Diseases (2004)

<h3>Objective.</h3> The lymphocytic infiltrates of minor salivary gland (MSG) lesions of Sjögren syndrome (SS) vary in grade and composition and are generally thought to develop in stepwise manner. Their progression over time is not well defined. <h3>Methods.</h3> We studied repetitive MSG biopsy specimens from 28 patients with primary SS. <h3>Results.</h3> The infiltration grade and prevalence of the major infiltrating cell types (T and B cells, macrophages, dendritic cells, natural killer cells) remained largely unchanged during a median 55 month biopsy time interval followup (quartiles 42–81). <h3>Conclusion.</h3> We found significant disease progression involving the development of mucosa-associated lymphoid tissue lymphoma in patients expressing adverse serologic prognostic factors, such as low serum C4 complement levels and cryoglobulinemia.
Percutaneous absorption in experimental epidermal disease
Authors: ANNE E. SOLOMON, N.J. LOWE
Journal: British Journal of Dermatology (1979)

Little is known about the absorption of topical drugs in epidermal disease associated with epidermal proliferation and altered keratinization. An abnormal hairless mouse epidermis was produced by three different methods: ultraviolet light irradiation, topical vitamin A acid and topical acetic acid. An increased epidermal thickness resulted and the in vitro percutaneous absorption of 0.1% (4‐ 14C) hydrocortisone was found to be increased when compared with normal hairless mouse epidermis. This is evidence for defective skin barrier function in experimental epidermal disease.
How Cells Respond to Interferons
Authors: Vincenzo Pitini, Carmela Arrigo, Giuseppe Altavilla
Journal: Journal of Clinical Oncology (2010)

TO THE EDITOR: Burchert et al have written an interesting and informative article about the sustained molecular response with interferon alfa (IFN) maintenance after induction therapy with imatinib plus IFNin patients with chronic myeloid leukemia (CML). The authors have concluded that IFNstimulates autologous cytotoxic T cells to specifically recognize a serine protease that is a BCR/Abl-dependent antigen and thus these cells are capable of specifically eliminating CML progenitors. In their article, Burchert et al develop the concept of an upfront imatinib/IFNcombination therapy aimed at obtaining a major molecular response followed by IFNmonotherapy to maintain this remission. Furthermore, only the discontinuation of imatinib after debulking may hypothetically release the full immune-stimulatory potential of IFN. Even if we substantially agree on what has been claimed by Burchert et al, we would like to discuss some points in greater detail. A recent observation seems to imply a proliferative effect of IFNon hematopoietic stem cells, suggesting a potential therapeutic application of IFNs in shifting dormant yet viable cancer cells into the cell cycle to increase their susceptibility to cytotoxic chemotherapy or target therapy. Furthermore, it seems that a short-term exposure of dormant hematopoietic cells to IFNpushes them out of dormancy into an active state of proliferation, whereas long-term exposure affects their function but does not directly eliminate hematopoietic stem cells. If this is true, one should assume that the current view of the standard care in CML is wrong and should be revised; in other words, these results increase confusion. Nevertheless, these two separate lines of evidence suggest two different challenges to the current view of standard care in CML. Briefly, if we assume that IFN targets residual BCR/Abl-positive cells that may be insensitive to imatinib therapy, a sequence of imatinib/IFN–based first-line therapy followed by IFN maintenance should result in sustained remission in the majority of patients; whereas if we hypothesize that IFNpromotes the proliferation of CML stem cells, we should develop a continued sequential therapy with IFN to recruit dormant CML stem cells and a subsequent imatinib therapy for the elimination of committed CML progenitors. However, in reality, although IFNhas been around for many years, we still do not know the mechanism by which it elicits its antileukemic effect in CML; thus, only when it is possible to better determine the mechanism by which IFNimparts its antileukemic effect on CML may we then be able to design a more intelligent approach to administering this drug.
STUDIES IN TISSUE SPECIFICITY
Authors: James B. Murphy
Journal: The Journal of Experimental Medicine (1914)

Rat tumors and other tissues of foreign species grow actively in the chick embryo until the onset of a refractory period. Grafts of rat sarcoma established and growing actively at the onset of this period show a rapid cessation of growth between the 18th and 19th days of incubation. This is followed by a widespread degeneration of the rat cells and a marked activity of the connective tissue elements in the embryonal tissue round about. An occasional specimen may show small mononuclear infiltration or rarely accumulations of polymorphonuclear cells in the neighborhood of the strange tissue. During the 20th and 21st days the connective tissue capsule increases rapidly, invading the graft and replacing it. The foreign cells disintegrate rapidly and by the 22d day have practically all disappeared. The period at which the established graft begins to degenerate, namely the 19th to the 20th day of incubation, is the one on which grafts of foreign tissue will no longer take when implanted in the embryo. The cells at the edge of the graft of foreign tissue survive for a time. There is a rapid formation of a connective tissue capsule and an invasion of the grafts. The foreign cells here practically all have disappeared by the 22d day, leaving a mass of connective tissue. The absence of a round cell infiltration is the most marked difference in the process in the embryo as compared with that in the adult chicken. The process about the grafts in newly hatched chicks is characterized by a more active response of the connective tissue than in the adult and a more pronounced round cell infiltration than in the embryo.
Depression of proximal tubular sodium reabsorption in the dog in response to renal beta adrenergic stimulation by isoproterenol
Authors: John R. Gill, Alfred G. T. Casper
Journal: Journal of Clinical Investigation (1971)

Water diuresis was produced in anesthetized hypophysectomized, cortisone-treated dogs by infusion of 2.5% dextrose. Alpha adrenergic blockade of the left kidney produced by infusion of phenoxybenzamine in the left renal artery was associated with a significantly (P < 0.05) greater rate of urine flow (V) and free water excretion (C(H2O)) in the left kidney than in the right despite similar glomerular filtration rates (GFR) (17 +/- 1.3 ml/min, left; 18 +/-0.9 ml/min, right). Sodium excretion (U(Na)V) was similar in the two kidneys (3 and 5 muEq/min). When beta adrenergic stimulation of the left kidney was superimposed on alpha blockade by the addition of isoproterenol to the left renal artery infusate, GFR remained unchanged and similar in the two kidneys, as V and C(H2O) increased significantly (P < 0.01) in the left kidney but not in the right. When isoproterenol was discontinued, V and C(H2O) returned towards control in the left kidney and remained unchanged in the right. The ratios of the left kidney to the right during control, isoproterenol, and postcontrol were 1.22, 1.65, and 1.35, respectively, for V and 1.36, 1.90, and 1.44, respectively, for C(H2O). Sodium excretion remained unchanged and similar in the two kidneys throughout the study. The results indicate that blockade of alpha adrenergic activity inhibits the increased proximal tubular sodium reabsorption which anesthesia induces in the dog. Beta adrenergic stimulation appears to decrease proximal tubular sodium reabsorption but does not prevent virtually complete reabsorption of the increased quantity of delivered sodium by the ascending limb of the loop of Henle and the distal tubule. These changes in sodium reabsorption presumably are not associated with changes in colloid osmotic pressure or hydrostatic pressure in the peritubular capillary inasmuch as cortical and non-cortical plasma flow, filtration fraction, and mean arterial pressure in the left kidney were unchanged. Thus, isoproterenol probably produced its effects through a direct action on the renal tubule, possibly through the mediation of the adenyl cyclase system.
Cardiovascular Disease: Rise, Fall, and Future Prospects
Authors: Russell V. Luepker
Journal: Annual Review of Public Health (2011)

Cardiovascular disease (CVD) became the leading cause of chronic disease morbidity and mortality in industrialized countries in the twentieth century. In many nations, it peaked and began to decline, while in developing countries it is rising. The contributions of risk factors, sociocultural changes, and medical care are debated, but all play a role in understanding these disease patterns. Public health approaches such as dietary change along with widespread use of medications such as aspirin, statins, diuretics, and beta-blockers may impact future trends in this chronic disease epidemic.
Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy.
Authors: C B Treasure, J A Vita, D A Cox, R D Fish, J B Gordon, G H Mudge, W S Colucci, M G Sutton, A P Selwyn, R W Alexander
Journal: Circulation (1990)

Dilator reserve of the coronary microvasculature is diminished in patients with dilated cardiomyopathy. Although increased extravascular compressive forces, tachycardia, and increased myocardial mass can explain some impairment, recent evidence suggests the possibility of intrinsic microvascular disease. We tested the hypothesis that impairment of endothelium-dependent dilation of the microvasculature could be a contributing mechanism. We infused the endothelium-dependent dilator acetylcholine (Ach) (10(-8) to 10(-6) M) and the smooth muscle vasodilator adenosine (AD) (10(-6) to 10(-4) M) into the left anterior descending coronary artery in eight patients with dilated cardiomyopathy (mean ejection fraction, 28%) and seven controls (atypical chest pain). Small vessel resistance was assessed by measuring coronary blood flow (CBF) at constant arterial pressure with a Doppler velocity catheter (corrected for cross-sectional area by angiography). With Ach, control patients increased CBF 232 +/- 40% (mean +/- SEM), whereas CBF did not significantly change in cardiomyopathy patients (41 +/- 24%) (p less than 0.0001, control vs. cardiomyopathy). With AD, control patients increased CBF 422 +/- 56% and cardiomyopathy patients increased CBF 268 +/- 43% (p = 0.13). An index of the proportion of coronary flow reserve attributable to endothelium-dependent vasodilation was obtained by standardizing each patient's Ach dose response to his maximal AD flow response. In seven control patients receiving both Ach and AD, 56 +/- 9% of the maximal AD flow response was attained with the endothelium-dependent vasodilator Ach, whereas in seven cardiomyopathy patients receiving both Ach and AD, only 23 +/- 14% of the maximal AD response was attained (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
High systemic bone mineral density increases the risk of incident knee OA and joint space narrowing, but not radiographic progression of existing knee OA: the MOST study
Authors: M C Nevitt, Y Zhang, M K Javaid, T Neogi, J R Curtis, J Niu, C E McCulloch, N A Segal, D T Felson
Journal: Annals of the Rheumatic Diseases (2009)

Objectives: Previous studies suggest that high systemic bone mineral density (BMD) is associated with incident knee osteoarthritis (OA) defined by osteophytes but not with joint space narrowing (JSN), and are inconsistent regarding BMD and progression of existing OA. The association of BMD with incident and progressive tibiofemoral OA was tested in a large prospective study of men and women aged 50–79 years with or at risk for knee OA. Methods: Baseline and 30-month weight-bearing posteroanterior and lateral knee radiographs were scored for Kellgren-Lawrence (K-L) grade, JSN and osteophytes. Incident OA was defined as the development of K-L grade ⩾2 at follow-up. All knees were classified for increases in grade of JSN and osteophytes from baseline. The association of gender-specific quartiles of baseline BMD with risk of incident and progressive OA was analysed using logistic regression, adjusting for covariates. Results: The mean (SD) age of 1754 subjects was 63.2 (7.8) years and body mass index was 29.9 (5.4) kg/m 2 . In knees without baseline OA, higher femoral neck and whole body BMD were associated with an increased risk of incident OA and increases in grade of JSN and osteophytes (p&lt;0.01 for trends); adjusted odds were 2.3–2.9-fold greater in the highest compared with the lowest BMD quartiles. In knees with existing OA, progression was not significantly related to BMD. Conclusions: In knees without OA, higher systemic BMD was associated with a greater risk of the onset of JSN and K-L grade ⩾2. The role of systemic BMD in early knee OA pathogenesis warrants further investigation.