tbuckley/cabot-search huggingface dataset:
Homocellular Conduction Along Endothelium and Smooth Muscle of Arterioles in Hamster Cheek Pouch
Authors: Stéphane Budel, Iain S. Bartlett, Steven S. Segal
Journal: Circulation Research (2003)

We investigated roles for homocellular (endothelium or smooth muscle) and heterocellular (myoendothelial) conduction pathways along hamster cheek pouch arterioles in vivo (n=64; diameter, 33+/-1 microm). Endothelium-dependent and -independent vasoactive agents were delivered from micropipettes (0.5 or 1 second pulse) onto an arteriole while observing diameter changes at defined distances along the vessel. Acetylcholine (ACh) produced maximal diameter (63+/-1 microm) locally and vasodilation conducted rapidly ( approximately 10 microm response at 2 mm, <1 second). Responses to bradykinin (BK) were similar, whereas sodium nitroprusside produced maximal dilation locally without conduction. KCl evoked biphasic conduction of vasoconstriction and vasodilation, whereas phenylephrine (PE) produced conducted vasoconstriction. Disrupting the integrity of endothelium as a conduction pathway using focal light-dye treatment (LDT) abolished conducted vasodilation to BK and to KCl but not to ACh. Disruption of smooth muscle integrity with LDT abolished conducted vasoconstriction with no effect on conducted vasodilation. After LDT of respective cell layers at sites 1 mm apart, vasodilation to ACh conducted past disrupted smooth muscle or disrupted endothelium, but not beyond both sites in series. The loss of conduction after selective LDT indicates a lack of effective myoendothelial coupling along the arteriolar wall. During NO synthase inhibition (L-NA, 100 micromol/L), conducted vasodilation was abolished to BK and to KCl yet remained intact to ACh. However, after LDT of smooth muscle, L-NA inhibited conduction to ACh by 60%. Thus, conduction of vasodilation entails a wave of NO release along arteriolar endothelium that is masked when smooth muscle provides a parallel conduction pathway.
III. Manic-Depressive Reactions
Authors: EARL D. BOND, HAROLD H. MORRIS
Journal: American Journal of Psychiatry (1954)

1. A main purpose has been to build a "control" series of 567 consecutive manic-depressive cases under hospital treatment before the advent of shock methods (1925-34). Recovery rates are found to be 59% on discharge, 55% after one year, and 64½% after 5 years. 2. A comparison with 563 consecutive cases under the same hospital treatment with EST available (1940-46) and used in about ¾ of these cases suffers because less than one-half could be followed for 5 (war) years. However, the recovery rates are 72% on discharge, 71% after one year, and 66% after 5 years. 3. In the control group the average stay in the Pennsylvania Hospital for recovered cases was 4.5 months; in the later group recovered patients (¾ of them treated with EST) had an average stay of 2.3 months. 4. Over half of all cases who recovered in both series remained well for 5 years or more. The EST series showed more breakdowns in those who could be followed. 5. The usefulness of electric shock therapy in shortening attacks is clear. 6. The importance of emphasizing "shortening the attack" is shown by a look at those patients listed as in fair condition with a minor defect—or much improved. There are more of these in the control series and there 135 cases would add nearly 24% to the proportion of good results on discharge. In 1940-46 there were 97 cases or only 17% to be added. But again in this group which might be called "much improved" the controls averaged 4.8 months' hospital stay while the advent of EST reduced the time to 2.3 months.
Elevated remnant-like lipoprotein particles in impaired glucose tolerance and type 2 diabetic patients.
Authors: N Watanabe, T Taniguchi, H Taketoh, Y Kitagawa, H Namura, N Yoneda, Y Kurimoto, S Yamada, Y Ishikawa
Journal: Diabetes Care (1999)

OBJECTIVE: Impaired glucose tolerance (IGT) in association with insulin resistance is considered to be a risk factor for atherosclerosis. Thus, patients with IGT may have abnormal lipid and lipoprotein profiles. The purpose of this study was to investigate presence of remnant-type hyperlipoproteinemia in patients with IGT. RESEARCH DESIGN AND METHODS: Serum levels of remnant-like lipoprotein particles (RLP) were measured in 541 subjects (362 men and 179 women, age 53 +/- 7.9 years) who visited our health center for routine medical examinations. We measured RLP cholesterol (RLP-C) and RLP triglycerides (RLP-TG) using immunoaffinity gel containing monoclonal anti-human apoproteins A-I (H-12) and B-100 (JI-H) antibodies. After a 75-g oral glucose tolerance test, subjects were divided into three groups: normal, IGT, and type 2 diabetic. RESULTS: After matching for sex, age, and body weight, serum RLP-C in normal, IGT, and diabetic groups were 4.2 +/- 1.7, 6.2 +/- 3.4, and 6.2 +/- 4.2 mg/dl, respectively. The corresponding RLP-TG values were 16.7 +/- 9.2, 28.0 +/- 19.1, and 29.0 +/- 27.2 mg/dl. We found that RLP-C and RLP-TG values were significantly higher in the IGT and diabetic groups compared with the normal group (P &amp;lt; 0.001). In the same order, total serum cholesterol levels were 206 +/- 29, 205 +/- 34, and 206 +/- 34 mg/dl and LDL cholesterol levels were 127 +/- 27, 124 +/- 34, and 123 +/- 34 mg/dl, showing no marked difference in these groups. However, serum levels of triglyceride were higher in the IGT and diabetes groups (155 +/- 76 and 151 +/- 81 mg/dl vs. 106 +/- 41 mg/dl; P &amp;lt; 0.0001). Further, the incidence of remnant hyperlipoproteinemia in normocholesterolemic subjects was up to four times higher in IGT and diabetic groups compared with the normal group. CONCLUSIONS: High serum RLP-C and RLP-TG levels in IGT and diabetic patients may represent an increased risk of atherosclerosis in these patients.
Neurobehavioural sequelae of cardiopulmonary b ypass
Authors: Ola A Selnes, Maura A Goldsborough, Louis M Borowicz, Guy M McKhann
Journal: The Lancet (1999)

The development of coronary artery bypass grafting (CABG) and its effect on angina is the product of a series of technical and scientific advances. Despite these advances, however, adverse neurobehavioural outcomes continue to occur. Stroke is the most serious complication of CABG, but studies that have identified demographic and medical risk factors available before surgery are an important advance. Short-term cognitive deficits are common after CABG, but may not be specific to this procedure. However, deficits in some cognitive areas such as visuoconstruction persist over time, and may reflect parieto-occipital watershed area injury secondary to hypoperfusion or embolic factors. Risk factors for cognitive decline may be time dependent, with short-term studies identifying factors that differ from those of long-term studies. Patients with depression before surgery are likely to have persistent depression afterwards. However, depression does not account for the cognitive decline after CABG. Since CABG is increasingly done in older patients with more comorbidity, the challenge is to identify patients at risk of adverse neurocognitive outcomes and to protect them by modification of the surgical procedure or by effective medical therapy.
Factors related to the failure of endoscopic injection therapy for bleeding gastric ulcer.
Authors: E Brullet, R Campo, X Calvet, D Coroleu, E Rivero, J Simo Deu
Journal: Gut (1996)

BACKGROUND: Although endoscopic injection therapy is effective in controlling initial haemorrhage from peptic ulcer, between 10% to 30% of patients suffer rebleeding. AIM: To assess the factors that may predict the failure of endoscopic injection in patients bleeding from high risk gastric ulcer. SUBJECTS: One hundred and seventy eight patients admitted for a gastric ulcer with a bleeding or a non-bleeding visible vessel were included. METHODS: Patients received endoscopic therapy by injection for adrenaline and polidocanol. Twelve clinical and endoscopic variables were entered into a multivariate logistic regression model to ascertain their significance as predictive factor of therapeutic failure. RESULTS: Eighty seven per cent (155 of 178) of patients had no further bleeding after endoscopic therapy. Endoscopic injection failed in 23 (13%) patients: 20 (12%) continued to bleed or rebleed, and three (1%) patients could not be treated because of inaccessibility of the lesion. Logistic regression analysis showed that therapeutic failure was significantly related to: (1) the presence of hypovolaemic shock (p = 0.09, OR 2.38, 95% CI: 0.86, 6.56), (2) the presence of active bleeding at endoscopy (p = 0.02, OR 2.98, 95% CI: 1.12, 7.91), (3) ulcer location high on the lesser curvature (p = 0.04, OR 2.79, 95% CI: 1.01, 7.69), and (4) ulcer size larger than 2 cm (p = 0.01, OR 3.64, 95% CI: 1.34, 9.89). CONCLUSION: These variables may enable identification of those patients bleeding from gastric ulcer who would not benefit from injection therapy.
Effectiveness of Early Antiretroviral Therapy Initiation to Improve Survival among HIV-Infected Adults with Tuberculosis: A Retrospective Cohort Study
Authors: Molly F. Franke, James M. Robins, Jules Mugabo, Felix Kaigamba, Lauren E. Cain, Julia G. Fleming, Megan B. Murray
Journal: PLoS Medicine (2011)

Background Randomized clinical trials examining the optimal time to initiate combination antiretroviral therapy (cART) in HIV-infected adults with sputum smear-positive tuberculosis (TB) disease have demonstrated improved survival among those who initiate cART earlier during TB treatment. Since these trials incorporated rigorous diagnostic criteria, it is unclear whether these results are generalizable to the vast majority of HIV-infected patients with TB, for whom standard diagnostic tools are unavailable. We aimed to examine whether early cART initiation improved survival among HIV-infected adults who were diagnosed with TB in a clinical setting. Methods and Findings We retrospectively reviewed charts for 308 HIV-infected adults in Rwanda with a CD4 count≤350 cells/µl and a TB diagnosis. We estimated the effect of cART on survival using marginal structural models and simulated 2-y survival curves for the cohort under different cART strategies:start cART 15, 30, 60, or 180 d after TB treatment or never start cART. We conducted secondary analyses with composite endpoints of (1) death, default, or lost to follow-up and (2) death, hospitalization, or serious opportunistic infection. Early cART initiation led to a survival benefit that was most marked for individuals with low CD4 counts. For individuals with CD4 counts of 50 or 100 cells/µl, cART initiation at day 15 yielded 2-y survival probabilities of 0.82 (95% confidence interval: [0.76, 0.89]) and 0.86 (95% confidence interval: [0.80, 0.92]), respectively. These were significantly higher than the probabilities computed under later start times. Results were similar for the endpoint of death, hospitalization, or serious opportunistic infection. cART initiation at day 15 versus later times was protective against death, default, or loss to follow-up, regardless of CD4 count. As with any observational study, the validity of these findings assumes that biases from residual confounding by unmeasured factors and from model misspecification are small. Conclusions Early cART reduced mortality among individuals with low CD4 counts and improved retention in care, regardless of CD4 count. Please see later in the article for the Editors' Summary
GP is allowed to practise again after affair with patient
Authors: Clare Dyer
Journal: BMJ (2014)

<h3>Introduction</h3> Refractory chronic cough has a significant negative impact on HRQoL. There are currently limited effective antitussive therapies. Few studies have explored the effectiveness of nonpharmacological interventions for refractory chronic cough. This study investigated the efficacy of PSALTI on HRQoL for people with refractory chronic cough in a multi-centred RCT. <h3>Methods</h3> Participants were recruited across five NHS hospitals trusts. 76 participants were randomised to PSALTI or placebo (equal attention) intervention. PSALTI consisted of education, laryngeal hygiene and hydration advice, cough control techniques and psycho-educational counselling. Placebo consisted of general education on exercise, diet, stress and relaxation. Both groups attended 4 weekly sessions of 1:1 therapy. HRQoL was measured at baseline, four weeks (end of treatment) and 3 month follow up by Leicester cough questionnaire (LCQ). Cough reflex sensitivity was assessed at baseline and four weeks by capsaicin cough challenge (C2, C5, concentration that caused first urge to cough (Cu)) and was analysed by geometric means (GM). Outcomes between groups were analysed using ANCOVA. <h3>Results</h3> The PSALTI (n = 35) and Placebo groups (n = 41) were well matched (p &gt; 0.05) for age [mean (SD)] 58(15) vs. 56(11) years; gender 71% vs 63% females; cough duration [median (IQR)] 60(30 to 126) vs 48(24 to 126) months and baseline LCQ [mean (SD)] 10.4(3.6) vs 11.9(3.5). At four weeks HRQoL improved in both groups, mean LCQ increase in PSALTI was 3.4 (95% CI 2.26 to 4.55) vs placebo 1.7 (95% CI 0.78 to 2.54); difference in LCQ change between groups was 1.5 (95% CI 0.27 to 7.31, p = 0.02) points more on average in the PSALTI group. This effect is greater than the MCID for LCQ and was sustained at 3 months (mean difference change between groups after 4 weeks to 3 months was -0.28 (95% CI -1.83 to 1.38). There was a significant increase in Cu in the PSALTI group compared to placebo (GM(SD) change 2 µm (5.07) vs 0.612 µm (3.26), p = 0.02). There was no significant difference in cough reflex sensitivity between the groups (C2, p = 0.46; C5, p = 0.74). <h3>Conclusions</h3> PSALTI significantly improved HRQoL compared with equal attention placebo intervention and this improvement was sustained at three months. PSALTI also significantly increased Cu compared to placebo.
Some Environmental Contaminants Influence Motor and Feeding Behaviors in the Ornate Wrasse ( <i>Thalassoma pavo</i> ) via Distinct Cerebral Histamine Receptor Subtypes
Authors: Giuseppina Giusi, Rosa Maria Facciolo, Raffaella Alò, Antonio Carelli, Maria Madeo, Pietro Brandmayr, Marcello Canonaco
Journal: Environmental Health Perspectives (2005)

Common environmental contaminants such as heavy metals and pesticides pose serious risks to behavioral and neuroendocrine functions of many aquatic organisms. In the present study, we show that the heavy metal cadmium and the pesticide endosulfan produce such effects through an interaction of specific cerebral histamine receptor subtypes in the teleost ornate wrasse (Thalassoma pavo). Treatment of this teleost with toxic cadmium levels for 1 week was sufficient to induce abnormal swimming movements, whereas reduced feeding behaviors were provoked predominantly by elevated endosulfan concentrations. In the brain, these environmental contaminants caused neuronal degeneration in cerebral targets such as the mesencephalon and hypothalamus, damage that appeared to correlate with altered binding levels of the three major histamine receptors (subtypes 1, 2, and 3). Although cadmium accounted for reduced binding activity of all three subtypes in most brain regions, it was subtype 2 that seemed to be its main target, as shown by a very great (p < 0.001) down-regulation in mesencephalic areas such as the stratum griseum central layer. Conversely, endosulfan provided very great and great (p < 0.01) up-regulating effects of subtype 3 and 1 levels, respectively, in preoptic-hypothalamic areas such as the medial part of the lateral tuberal nucleus, and in the suprachiasmatic nucleus. These results suggest that the neurotoxicant-dependent abnormal motor and feeding behaviors may well be tightly linked to binding activities of distinct histamine subtypes in localized brain regions of the Thalassoma pavo.
PTEN-deficient intestinal stem cells initiate intestinal polyposis
Authors: Xi C He, Tong Yin, Justin C Grindley, Qiang Tian, Toshiro Sato, W Andy Tao, Raminarao Dirisina, Kimberly S Porter-Westpfahl, Mark Hembree, Teri Johnson, Leanne M Wiedemann, Terrence A Barrett, Leroy Hood, Hong Wu, Linheng Li
Journal: Nature Genetics (2007)
A7.2 Identification of predictive micro-RNAs of progression from PRE-RA systemic autoimmunity to development of RA using matched serum samples
Authors: L Ouboussad, L Hunt, EMA Hensor, C Wong, P Emery, MF McDermott, MH Buch
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Recent EULAR recommendations for terminology of rheumatoid arthritis (RA) at-risk groups recognise those with systemic autoimmunity associated with pre-clinical RA, characterised by the presence of ACPA. Identification of predictors of progression from this pre-RA state to the RA syndrome would have clinical utility. MicroRNA (miRNA) are highly conserved small, non-coding RNA that serve as transcriptional negative regulators; with growing evidence that they contribute to the pathogenesis of human diseases, including RA. Our study aimed to identify serum miRNA that predict progression from pre-RA to RA using global profiling. <h3>Materials and methods</h3> Matched serum samples were used from 12 subjects presenting with CCP positivity only (CCP+) that were followed to the point of development of RA (Very Early RA, VERA). Samples were also obtained from 9 subjects with Early RA (ERA), symptom history of ≤ 12 months; 12 healthy controls formed a control group (HC). TaqMan low density MicroRNA Array Cards was applied to examine the expression of 754 human miRNAs and controls in the 4 cohorts: miRNA with a 4-fold change in expression (down or up-regulation) were selected as candidate biomarkers for RA progression. Heatmaps were plotted using unsupervised hierarchical clustering analysis, permitting separation of cohorts into groups according to miRNA expression levels. A validation analysis of the miRNAs of interest was conducted on a further 12 HC, 12 CCP+ individuals who did not progress and 12 CCP+ individuals that did progress, using custom miRNA array cards. <h3>Results</h3> After adequate normalisation and data analysis, serum miRNA profiling identified 22 candidate miRNA that were dysregulated when comparing their relative expression from one of the studied cohorts to another. We have identified a four-miRNA signature dysregulated between the matched CCP+ to VERA cohorts. In addition, hierarchical clustering revealed a clear differential miRNA expression between the cohorts. The validation study consists of evaluating expression levels of the 22 miRNA and also 9 miRNA that have been previously implicated in RA (such as miR-155 and miR-146a) using custom array cards in order to confirm their involvement in RA pathogenesis; the results of which are awaited. <h3>Conclusions</h3> Using a comprehensive MicroRNA array approach this study is a first to use matched pre-RA and VERA serum samples to identify dysregulated miRNA expression as biomarkers predictive of progression along this transition phase. We have identified 4 miRNAs in particular that could be potential diagnostic markers of RA, which we are about to validate further.
The Effectiveness of Long-Term Treatment of Malignant Hypertension
Authors: HARRIET P. DUSTAN, ROLAND E. SCHNECKLOTH, A. C. CORCORAN, IRVINE H. PAGE
Journal: Circulation (1958)

A survey is reported of the courses of 84 patients who presented the syndrome of malignant hypertension and who have been under treatment with potent antihypertensive drugs. Among these, 70 per cent survived 1 year of observation, 50 per cent 3 years, 33 per cent 5 years, and 26 per cent 6 years. These survival rates represent substantial therapeutic gains over survival rates in the untreated series of Keith, Wagener, and Barker. The reported first-year survival rate is weighted by the untoward complication of hexamethonium pneumonitis, and current survival is greater than in the estimate presented. Other causes of death are (1) rapidly or (2) delayed or slowly progressive renal failure and (3) complications of atherosclerosis. The first is usually associated with poor control of blood pressure. It seems merely an attenuation of the usual course of malignant hypertension. The syndrome of delayed or slowly progressive renal failure is associated with diffuse occlusive fibrous intimal hyperplasia of major renal arteries. Among the complications of atherosclerosis, cerebral hemorrhage was the most common and was associated with poor control of blood pressure level, while myocardial infarction, the next most common, was not. It may be that the coronary arteries, like the renal, are subject to progressive occlusive disease in some patients with treated malignant hypertension. It is not clear whether this process represents a continuation in vessels larger than arterioles, of a basic vascular disease or a delayed response on the part of the arteries to preexisting severe hypertension. Survival is improved in patients who undertake treatment before malignant hypertension has caused extensive vascular damage. Patients who present themselves for treatment with evidences of severe renal damage generally do not survive for long periods. However, several such have maintained active lives for many months and years. Hence treatment should be withheld only in the most desperate circumstances.
Transmural myocardial blood flow in a canine model of coronary artery bridging.
Authors: A E Mays, P A McHale, J C Greenfield
Journal: Circulation Research (1981)

The purpoae of the present study was to develop a canine model of coronary artery bridging and assess transmural myocardial pcrfusion in this setting.Six adult mongrel dogs were chronically instrumented with aortic and left atrial pressure catheters, a right ventricular bipolar pacing electrode, and a left circumflex coronary artery electromagnetic flow probe and balloon occluder.Seven to 10 days postoperatively, the animals were studied in the awake state.Myocardial bridlng was modeled by totally occluding left circumflex coronary artery inflow for systole (S) only, systole plu* one-sixth, one-third, and one-half of diastole (D) by means of an ECG-triggered solenoid valve, at a paced heart rate of 120 beats/min.Regional myocardial flow was determined during each intervention with 3-to 10-ftm radiolabeled microspheres.No change in systemic hemodynamics was noted during the course of any occlusion intervention.However, mean left circumflex coronary flow was significantly reduced during occlusion of S + 1/3 D and S + 1/2 D, and this was associated with decreased flow to the endocardial layers.Peripheral left circumflex coronary artery pressure was assessed in an additional series of five open-chest dogs identically instrumented with the addition of a coronary artery pressure catheter inserted distal to the balloon occluder.During the occlusion of S + 1/2 D, the peripheral coronary pressure markedly decreased to a minimum value of 26 ± 5 mm Hg and a mean value of 53 ± 10 mm Hg.Thus, during the inflow time allowed by this intervention, coronary perfusion pressure was reduced markedly.If this animal model of myocardial bridging is appropriate, these data suggest that, in the rare patient with symptomatic myocardial bridging, occlusion of a coronary artery during systole and a significant portion of diastole results in a decrease in mean flow and a maldistribution of transmural flow.Thia blood flow deficit is related both to reduced inflow time and decreased perfusion pressure CircRes 49: 726-732, 1981