tbuckley/cabot-search huggingface dataset:
Long-Term Localized High-Frequency Electric Stimulation Within the Myocardial Infarct
Authors: Rupak Mukherjee, William T. Rivers, Jean Marie Ruddy, Robert G. Matthews, Christine N. Koval, Rebecca A. Plyler, Eileen I. Chang, Risha K. Patel, Christine B. Kern, Robert E. Stroud, Francis G. Spinale
Journal: Circulation (2010)

Background— Disruption of the balance between matrix metalloproteinases (MMP) and MMP inhibitors (TIMPs) within a myocardial infarct (MI) contributes to left ventricular wall thinning and changes in regional stiffness at the MI region. This study tested the hypothesis that a targeted regional approach through localized high-frequency stimulation (LHFS) using low-amplitude electric pulses instituted within a formed MI scar would alter MMP/TIMP levels and prevent MI thinning. Methods and Results— At 3 weeks after MI, pigs were randomized for LHFS (n=7; 240 bpm, 0.8 V, 0.05-ms pulses) or were left unstimulated (UNSTIM; n=10). At 4 weeks after MI, left ventricular wall thickness (echocardiography; 0.89±0.07 versus 0.67±0.08 cm; P &lt;0.05) and regional stiffness (piezoelectric crystals; 14.70±2.08 versus 9.11±1.24; P &lt;0.05) were higher with LHFS than in UNSTIM. In vivo interstitial MMP activity (fluorescent substrate cleavage; 943±59 versus 1210±72 U; P &lt;0.05) in the MI region was lower with LHFS than in UNSTIM. In the MI region, MMP-2 levels were lower and TIMP-1 and collagen levels were higher with LHFS than in UNSTIM (all P &lt;0.05). Transforming growth factor-β receptor 1 and phosphorylated SMAD-2/3 levels within the MI region were higher with LHFS than in UNSTIM. Electric stimulation (4 Hz) of isolated fibroblasts resulted in reduced MMP-2 and MT1-MMP levels but increased TIMP-1 levels compared with unstimulated fibroblasts. Conclusions— These unique findings demonstrate that LHFS of the MI region altered left ventricular wall thickness and material properties, likely as a result of reduced regional MMP activity. Thus, LHFS may provide a novel means to favorably modify left ventricular remodeling after MI.
The Slope of the Segmental Stretch-Strain Relationship as a Noninvasive Index of LV Inotropy
Authors: Ruta Jasaityte, Piet Claus, Arco J. Teske, Lieven Herbots, Bart Verheyden, Ruxandra Jurcut, Frank Rademakers, Jan D'hooge
Journal: JACC. Cardiovascular imaging (2013)
Doctors should do more for drug addicts, committee says
Authors: O. Dyer
Journal: BMJ (2002)

Britain's doctors are not doing enough to care for drug misusers, according to a House of Commons committee report published last week.

The Home Affairs Select Committee, chaired by former Labour minister Chris Mullin, also concluded that an enforcement based approach to drug misuse was not working.

The committee declined, however, to recommend the legalisation of cannabis, suggesting instead that it be downgraded from a class B to a class C illegal substance. This change, already proposed by home secretary David Blunkett, is likely to be announced in the summer. He rejected the committee's proposal to downgrade ecstasy from …
Regulation of rat hepatic low density lipoprotein receptors. In vivo stimulation by growth hormone is not mediated by insulin-like growth factor I.
Authors: M Rudling, H Olivecrona, G Eggertsen, B Angelin
Journal: Journal of Clinical Investigation (1996)

Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to evaluate if these effects of GH on hepatic LDL receptors are direct or mediated by insulin-like growth factor I (IGF-I). Two models were studied in which substitution with GH is important for the regulation of hepatic LDL receptors: hypophysectomized rats receiving high-dose ethynylestradiol or challenge with dietary cholesterol. The hypophysectomized rats were hormonally substituted by infusion with dexamethasone and L-thyroxine, and either GH or IGF-I. In both models, GH was essential for maintaining normal expression of LDL receptors. In contrast, despite fully normalized plasma levels, IGF-I did not support the expression of hepatic LDL receptors. Analysis of plasma lipoproteins revealed that substitution with GH, but not with IGF-I, reduced LDL and intermediate density lipoproteins. In addition, determination of hepatic mRNA levels for apo B-100 and apo B-48 indicated that GH may be more effective than IGF-I in the promotion of apo B mRNA editing. In conclusion, GH has specific effects on hepatic LDL receptor expression and plasma lipoprotein levels that are not mediated by IGF-I.
No effect of coronary perfusion on regional myocardial function within the autoregulatory range in pigs. Evidence against the Gregg phenomenon.
Authors: R Schulz, B D Guth, G Heusch
Journal: Circulation (1991)

BACKGROUND The hypothesis that increases in coronary perfusion increase ventricular performance independently from providing enhanced oxygen supply ("Gregg phenomenon") remains controversial. METHODS AND RESULTS To study the physiological significance of changes in coronary perfusion on global and regional myocardial function in situ, the left anterior descending coronary artery of isoflurane-anesthetized swine was cannulated, and perfusion was varied. In one group of swine (n = 5), coronary arterial pressure was increased in four steps from 88 +/- 11 to 186 +/- 11 mm Hg by increasing the speed of the pump circuit providing coronary blood flow. No changes in left ventricular end-diastolic pressure, peak pressure, or maximum left ventricular dP/dt were observed. Subendocardial blood flow (by radiolabeled microspheres) increased from 0.96 +/- 0.27 to 2.04 +/- 0.73 ml/min/g without any increase in systolic wall thickening (by sonomicrometry) or myocardial oxygen consumption of the anterior myocardium. In a second group of swine (n = 8), coronary arterial pressure was kept constant and coronary blood flow was increased stepwise by intracoronary adenosine infusion. End-diastolic pressure, peak pressure, and maximum left ventricular dP/dt remained unchanged when coronary blood flow increased from 21.7 +/- 9.8 to 93.8 +/- 34.1 ml/min. Subendocardial blood flow increased from 0.89 +/- 0.26 to 3.28 +/- 1.02 ml/min/g, again without any increase in systolic wall thickening (45.6 +/- 8.6 versus 42.6 +/- 9.8%) and myocardial oxygen consumption (5.75 +/- 1.18 versus 5.87 +/- 1.67 ml/min/100 g). In a third group of swine (n = 10), coronary arterial pressure was lowered by intracoronary adenosine infusion during constant coronary inflow. Left ventricular hemodynamics remained unchanged. With a decrease in coronary arterial pressure from 130 +/- 25 to 71 +/- 14 mm Hg, no decreases in subendocardial blood flow and systolic wall thickening were observed. Only when coronary arterial pressure was further reduced to 57 +/- 13 mm Hg did systolic wall thickening fall to 25.7 +/- 9.9% (control, 31.1 +/- 11.1%), associated with a decrease in subendocardial blood flow from 1.17 +/- 0.39 to 0.87 +/- 0.52 ml/min/g. CONCLUSIONS Thus, the Gregg phenomenon plays no significant role within or above the autoregulatory pressure-flow range normally seen in anesthetized swine in situ.
Pathophysiologic Approach to Therapy in Patients With Newly Diagnosed Type 2 Diabetes
Authors: Ralph A. DeFronzo, Roy Eldor, Muhammad Abdul-Ghani
Journal: Diabetes Care (2013)

Two general approaches to the treatment of type 2 diabetes mellitus (T2DM) have been advocated. 1 ) A “guideline” approach that advocates sequential addition of antidiabetes agents with “more established use” (1); this approach more appropriately should be called the “treat to failure” approach, and deficiencies with this approach have been discussed (2). And 2 ) a “pathophysiologic” approach using initial combination therapy with agents known to correct established pathophysiologic defects in T2DM (3). Within the pathophysiologic approach, choice of antidiabetes agents should take into account the patient’s general health status and associated medical disorders. This individualized approach, which we refer to as the ABCD(E) of diabetes treatment (4), has been incorporated into the updated American Diabetes Association (ADA) guidelines (5).

Even though physicians must be cognizant of these associated conditions (ABCDE) when initiating therapy in newly diagnosed T2DM patients, we believe that the most important consideration is to select antidiabetes agents that correct specific pathophysiologic disturbances present in T2DM and that have complementary mechanisms of action. Although it has been argued that the pathogenesis of T2DM differs in different ethnic groups (6), evidence to support this is weak. Although the relative contributions of β-cell failure and insulin resistance to development of glucose intolerance may differ in different ethnic groups (6), the core defects of insulin resistance in muscle/liver/adipocytes and progressive β-cell failure (3) are present in virtually all T2DM patients and must be treated aggressively to prevent the relentless rise in HbA1c that is characteristic of T2DM.

In subsequent sections, we provide a review of the natural history of T2DM, specific pathophysiologic abnormalities responsible for T2DM, currently …
Renal Scintigraphy in a Patient with Pelvic Lipomatosis
Authors: EDWARD GOSFIELD, ALAN SIEGEL
Journal: Clinical Nuclear Medicine (1992)

A patient with a history of benign prostatic hypertrophy and pelvic lipomatosis was evaluated for pain and swelling of the abdomen and left leg. As part of his workup, renal imaging was performed and revealed medial deviation of the ureters, incomplete emptying of the collecting systems, and a pear-shaped bladder. Although these findings have been reported with other imaging modalities in patients with pelvic lipomatosis, they have not been described in renal scintigraphy. This constellation of findings should lead to the consideration of the diagnosis of pelvic lipomatosis.
Perceived Value of Providing Peer Reviewers With Abstracts and Preprints of Related Published and Unpublished Papers
Authors: Christopher L. Hatch
Journal: JAMA (1998)

Many journals provide peer reviewers with written instructions regarding review criteria, such as the originality of results, but little research has been done to investigate ways to improve or facilitate the peer review task.To assess the value that peer reviewers place on receipt of supplemental materials (eg, abstracts of related papers and preprints of related unpublished manuscripts).Questionnaire survey sent to all 733 peer reviewers recruited by the Journal of the National Cancer Institute to review 356 manuscripts consecutively sent out for review from February 24, 1997, through January 16, 1998. The inclusion of supplemental materials with manuscript review packages was optional.The peer reviewers' assessment of the actual or potential usefulness of supplemental materials on the performance of peer review.A total of 481 (66%) of 733 questionnaires were returned. Of the 471 respondents' questionnaires that could be used, 217 (46%) indicated that they received abstracts, and 44 (10%) of 458 respondents indicated that they received preprints. Higher proportions of peer reviewers who received supplemental materials than those who had not received them felt that they were (or would be) useful to them when reviewing the manuscript (63% [95% confidence interval (CI), 57%-69%] vs 45% [95% CI, 38%-52%]; P<.001) and to the peer review process in general (80% [95% CI, 75%-85%] vs 64% [95% CI, 58%-70%]; P<.001).The majority of respondents indicated that supplemental materials helped (or would have helped) them evaluate manuscripts and valued them more highly when they actually received them.
Temporal Response and Localization of Integrins β1 and β3 in the Heart After Myocardial Infarction
Authors: Mei Sun, M. Anne Opavsky, Duncan J. Stewart, Marlene Rabinovitch, Fayez Dawood, Wen-Hu Wen, Peter P. Liu
Journal: Circulation (2003)

Integrins are involved in structural remodeling and tissue repair. This study aimed to elucidate the role of the beta-integrins in cardiac remodeling after myocardial infarction (MI).The MI model was created by ligation of the left anterior descending coronary artery in rats. We detected cardiac integrins beta1 and beta3 gene expression (quantitative in situ hybridization) and protein production (Western blot and immunohistochemistry) and potential regulation by tumor necrosis factor (TNF) using neonatal ventricular myocytes and TNF-/- knockout mice. Integrins beta1 and beta3 gene expression and protein production were low in sham-operated hearts. After MI, the beta1 and beta3 mRNA and proteins were significantly increased at the site of MI at day 3, reached a peak at day 7, and gradually declined thereafter. Integrin beta1A localized primarily in fibroblasts and inflammatory cells, beta1D localized in myocytes, and integrin beta3 was associated primarily with endothelial and smooth muscle cells in peri-infarct vessels. In cultured myocytes, there was isoform transition from the adult beta1D to the fetal beta1A on exposure to TNF-alpha. This was confirmed in vivo in the peri-infarct myocytes, but the transition was voided in TNF-/--knockout mice.Integrins beta1 and beta3 are significantly activated in the infarcted myocardium. Integrin beta1 is active particularly at sites of inflammation and fibrosis, whereas integrin beta3 localizes to vessels in the peri-infarct zone in a temporally coordinated manner. Integrin beta1D to beta1A isoform transition in myocytes is regulated by TNF-alpha.
Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease.
Authors: M K Racke, A Bonomo, D E Scott, B Cannella, A Levine, C S Raine, E M Shevach, M Röcken
Journal: The Journal of Experimental Medicine (1994)

The properties and outcome of an immune response are best predicted by the lymphokine phenotype of the responding T cells. Cytokines produced by CD4+ T helper type 1 (Th1) T cells mediate delayed type hypersensitivity (DTH) and inflammatory responses, whereas cytokines produced by Th2 T cells mediate helper T cell functions for antibody production. To determine whether induction of Th2-like cells would modulate an inflammatory response, interleukin 4 (IL-4) was administered to animals with experimental allergic encephalomyelitis (EAE), a prototypic autoimmune disease produced by Th1-like T cells specific for myelin basic protein (MBP). IL-4 treatment resulted in amelioration of clinical disease, the induction of MBP-specific Th2 cells, diminished demyelination, and inhibition of the synthesis of inflammatory cytokines in the central nervous system (CNS). Modulation of an immune response from one dominated by excessive activity of Th1-like T cells to one dominated by the protective cytokines produced by Th2-like T cells may have applicability to the therapy of certain human autoimmune diseases.
Twice-Weekly Maintenance Therapy with Sulfadiazine-Pyrimethamine To Prevent Recurrent Toxoplasmic Encephalitis in Patients with AIDS
Authors: Daniel Podzamczer
Journal: Annals of Internal Medicine (1995)

Objective: To evaluate the efficacy of twice-weekly maintenance therapy with sulfadiazine-pyrimethamine to prevent toxoplasmic encephalitis relapse in patients with the acquired immunodeficiency syndrome (AIDS). Design: Randomized, open, multicenter trial. Patients were randomly assigned to receive sulfadiazine (500 mg) four times per day plus pyrimethamine (25 mg) plus folinic acid (15 mg) either daily (n = 60) or twice weekly (n = 45). Setting: 8 university teaching hospitals. Patients: Between February 1990 and June 1993, 105 patients with HIV infection were enrolled after each had had resolution of an acute episode of toxoplasmic encephalitis treated with sulfadiazine (1 g four times per day) plus pyrimethamine (50 mg/d) plus folinic acid (15 mg/d) for 4 to 8 weeks. Measurements: Clinical and biological evaluations done every 30 to 60 days. End points were toxoplasmic encephalitis relapse, death, and interruption of therapy due to adverse reactions. Results: After a median follow-up period of 11 months (range, 1 to 39 months), patients receiving the twice-weekly regimen had a higher rate of relapse than patients receiving the daily regimen (19.5 compared with 4.4 per 100 patient-years; incidence rate ratio, 4.36 [95% CI, 1.05 to 25.5]; P = 0.024). The estimated cumulative percentages of relapse at 12 months were 30% and 6%, respectively (P = 0.029), with an adjusted risk ratio (adjusted for age, sex, risk behavior, previous diagnosis of AIDS, Pneumocystis carinii pneumonia prophylaxis before initial episode of toxoplasmosis, CD4 cell count, baseline number of brain lesions, radiologic sequelae, and antiretroviral therapy during follow-up) of 5.6 (CI, 1.2 to 25.6; P = 0.028). Patients receiving the twice-weekly regimen had 1.6 times (CI, 0.9 to 2.9 times; P = 0.11) the adjusted risk for death of patients receiving the daily regimen. No statistical differences were found in the patients who stopped receiving the regimens due to adverse effects. No patient developed P. carinii pneumonia during the study period, even though 17 patients (10 receiving the daily regimen and 7 receiving the twice-weekly regimen) had had an episode of P. carinii pneumonia before study entry. Conclusions: At the given doses, a combination of sulfadiazine, pyrimethamine, and folinic acid was less effective when administered twice weekly than when administered daily, although the twice-weekly regimen was much more effective than historic controls.
The zebrafish udu gene encodes a novel nuclear factor and is essential for primitive erythroid cell development
Authors: Yanmei Liu, Linsen Du, Motomi Osato, Eng Hui Teo, Feng Qian, Hao Jin, Fenghua Zhen, Jin Xu, Lin Guo, Honghui Huang, Jun Chen, Robert Geisler, Yun-Jin Jiang, Jinrong Peng, Zilong Wen
Journal: Blood (2007)
Phenformin-Associated Lactic Acidosis Due to Imported Phenformin
Authors: Hua Chung Lu, Purvi P Parikh, Daniel L Lorber
Journal: Diabetes Care (1996)

OBJECTIVE To emphasize the continued incidence of phenformin-associated lactic acidosis. CASE REPORT We report a case of phenformin-associated lactic acidosis in a Chinese man who received phenformin while in China. Diagnosis was made; the patient was treated appropriately and survived. COMMENTS Phenformin-associated lactic acidosis may still occur in the U.S.
Childhood Asphyxiation by Choking or Suffocation
Authors: Susan P. Baker, Russell S. Fisher
Journal: JAMA (1980)

Medical examiner records were reviewed for 42 Maryland children younger than 10 years who died of asphyxiation from 1970 through 1978. Twelve children choked on food; six of these deaths involved hot dogs. Eight choked on nonfood objects. Size, shape, and consistency were important, with small, round, pliable products predominating. Twenty-two deaths resulted from suffocation, including four infants who died when plastic bags in their cribs or playpens pressed against their faces. Twelve of the 42 deaths resulted from problems that are now the subject of Consumer Product Safety Commission activity or regulations. Important problems not currently addressed include plastic bags, balloons, and foods that because of their shape or consistency are especially likely to cause asphyxiation.
Prophylactic Lidocaine in Acute MI
Authors: Alberto Volpi, Augusto Cavalli, Aldo Maggioni, Maria Grazia Franzosi, Gianni Tognoni
Journal: JAMA (1989)

<h3>To the Editor. —</h3> The excellent overview by MacMahon et al<sup>1</sup>on prophylactic lidocaine in suspected acute myocardial infarction includes one disturbing misquotation. The authors state: "With regard to survival after discharge from the hospital, nonfatal VF [ventricular fibrillation] following AMI [acute myocardial infarction] appears to be associated with a worse prognosis."<sup>2</sup>However, this was not the case in the GISSI trial, since an episode of primary ventricular fibrillation was shown to be a negative predictor of survival only in the hospital phase of infarction.<sup>2,3</sup>Indeed, after hospital discharge, the long-term prognosis of survivors was as good as for patients with comparable infarcts not complicated by primary ventricular fibrillation. Nonetheless, we agree with MacMahon and coworkers that our data raise the possibility that a reduction in ventricular fibrillation following prophylactic lidocaine in patients with suspected acute myocardial infarction might result in a beneficial effect on in-hospital survival.
Increasing Incidence of Hypoglycemic Coma in Children With IDDM
Authors: Matthias Egger, Sylvia Gschwend, George Davey Smith, Klaus Zuppinger
Journal: Diabetes Care (1991)

Objective To examine the incidence of hypoglycemic coma in children with insulin-dependent diabetes mellitus (IDDM) over 8 yr from 1981 to 1988 and to investigate the importance of residual β-cell function of HbA1 levels and other variables as risk factors for hypoglycemic coma. Research Design and Methods The study consisted of 155 children with IDDM aged &amp;lt; 16 yr at study entry. Mean age at onset of diabetes was 7.9 yr (range 1.1–15.6 yr). We made a prospective assessment of hypoglycemic coma episodes, with a standardized questionnaire, over a total observation time of 816.6 person-yr. Three monthly clinical and laboratory examinations, which included determinations of C-peptide and HbA1 levels, were conducted. We compared children with hypoglycemic coma (cases) with children without hypoglycemic coma (controls) in a case-control analysis matched for diabetes duration. Yearly incidence of hypoglycemic coma, calculated as the number of subjects having an attack in 1 yr divided by the cumulative number of person-years for that year, was measured. Univariate and multivariate odds ratios were calculated from logistic regression. Results Over the first 4 yr, the average yearly incidence was 4.4/100 person-yr compared with 7.4/100 person-yr during the later 4 yr (P &amp;lt; 0.0001). This tendency was accompanied by intensification of insulin treatment with an increase in the mean number of daily injections and a decrease in mean HbA1 levels. In the case-control analysis, absent residual β-cell function was the most important risk factor for hypoglycemic coma (adjusted odds ratio 7.8, 95% confidence intervals 2.0–31.2), followed by near-normal HbA1 levels (adjusted odds ratio 4.5, 95% confidence intervals 1.9–10.5). Conclusions In this group of children, improvement of glycemic control apparently led to an increase in the incidence of severe hypoglycemia. In children with recurrent hypoglycemic coma and undetectable C-peptide levels, it may be safer to aim for somewhat less tight glycemic control.
Notes on Fifteen Cases of Intussusception
Authors: C. P. B. Clubbe
Journal: BMJ (1897)

I33 5 dermal layers, causing dcsquamation of unhealthy epidermis ;and reproduction of a new covering, as observed in ichthyosis, psoriasis, dry chronic eczema, and also in some cases of znyxoedema and cretinism.Among its general effects I have found that in doses of 15 gr.daily it causes a pulse-rate of 120 to 14oper minute, -which in different subjects may be either of high or low -tension.But thyroid extract seems also to rapidly exhaust latent cardiac energy, for if the dose be unduly increased, or if the patient is not fully accustomed to it, then the heart soon tires, and the pulse, although still quick, is weakened so as -to induce irritability, depression, and tendency to syncope.
Development of social emotions and constructive agents
Authors: Aaron Ben Ze'ev, Keith Oatley
Journal: Behavioral and Brain Sciences (1996)

Abstract The psychology of emotions illuminates the questions of intentional capacities raised by Barresi &amp; Moore (B&amp;M). Complex emotions require the development of a sense of self and are based on social comparisons between mainly imagined objects. The fourth level in B&amp;M's framework requires something like a constructive agent rather than a mental agent.
DIFFERENCES IN OCCURRENCE OF DEVICE THERAPY IN ECHOCARDIOGRAPHIC RESPONDERS AND SUPER RESPONDER OF CARDIAC RESYNCHRONIZATION THERAPY
Authors: Aafke Van Der Heijden, Ulas Hoke, Jan Willem Borleffs, Joep Thijssen, Johannes van Rees, Enno Van Der Velde, Martin Schalij, Lieselot van Erven
Journal: Journal of the American College of Cardiology (2013)