tbuckley/cabot-search huggingface dataset:
Central Nervous System Control of Baroreceptor Reflexes in the Rabbit
Authors: P. I. KORNER, J. SHAW, M. J. WEST, J. R. OLIVER
Journal: Circulation Research (1972)

Aortic and inferior vena caval balloons were used to alter mean arterial blood pressure, pulse pressure ( PP ), and right atrial pressure ( RAP ) in unanesthetized rabbits and to reflexly evoke changes in heart period (pulse interval). Curves relating mean arterial blood pressure to heart period were compared in different groups of rabbits at similar Δ PP and Δ RAP . Median blood pressure ( BP 50 ), average gain (G), and heart period range (maximum to minimum heart period) were calculated from the S-shaped curves. The reflex was evoked from arterial baroreceptors and probably from cardiac and pulmonary baroreceptors. Curves relating mean arterial blood pressure and heart period differed with regard to BP 50 and G in sham-operated, thalamic, and pontine rabbits, indicating that suprabulbar centers normally play a role in the reflex. Curves from sham-operated and pontine rabbits treated with atropine also differed, suggesting suprabulbar control of sympathetic effectors. In intact rabbits, forebrain and diencephalic centers caused vagal and sympathetic effectors to respond over the same arterial blood pressure range, but, in pontine rabbits, the effectors responded over dissimilar ranges. In intact rabbits, changes in mean arterial blood pressure evoked reciprocal and nearly equal changes in vagal and sympathetic effectors, but, in pontine rabbits, a given pressure change altered heart period predominantly through one effector. In sham-operated rabbits, vagal effects on heart period were lower by a constant amount at every level of mean arterial blood pressure than they were in pontine rabbits, suggesting that suprabulbar centers exerted a tonic inhibitory effect on vagal motoneurons not involved in the reflex.
Medicine and torture.
Authors: A. van Es
Journal: BMJ (1992)

trials of mainly unopposed oestrogen in postmenopausal women appear to show highly significant reductions in both cardiovascular and all cause mortality from samples of a similar size to those of the major primary and secondary trials of lipid lowering drugs.'2-'5These results too deserve further evaluation by controlled clinical trials.But meanwhile the lack of evidence of significant reductions in all cause mortality by lipid lowering drugs,3'4 1 particularly in primary prevention trials, indicates that any favourable effect of lipid-lowering drugs on all cause mortality is at best small and of only marginal benefit to the individual.At present the cost-benefit uncertainties generated by the WHO clofibrate trial and its successors emphasise the importance of restricting the use of hypolipidaemic drugs to patients with established vascular disease and hyperlipidaemia or to asymptomatic patients with severe hyperlipidaemia at high risk of premature vascular disease where dietary measures have been ineffectual.
The Neural Correlates of Anomalous Habituation to Negative Emotional Pictures in Borderline and Avoidant Personality Disorder Patients
Authors: Harold W. Koenigsberg, Bryan T. Denny, Jin Fan, Xun Liu, Stephanie Guerreri, Sarah Jo Mayson, Liza Rimsky, Antonia S. New, Marianne Goodman, Larry J. Siever
Journal: American Journal of Psychiatry (2013)

Extreme emotional reactivity is a defining feature of borderline personality disorder, yet the neural-behavioral mechanisms underlying this affective instability are poorly understood. One possible contributor is diminished ability to engage the mechanism of emotional habituation. The authors tested this hypothesis by examining behavioral and neural correlates of habituation in borderline patients, healthy comparison subjects, and a psychopathological comparison group of patients with avoidant personality disorder.During fMRI scanning, borderline patients, healthy subjects, and avoidant personality disorder patients viewed novel and repeated pictures, providing valence ratings at each presentation. Statistical parametric maps of the contrasts of activation during repeated versus novel negative picture viewing were compared between groups. Psychophysiological interaction analysis was employed to examine functional connectivity differences between groups.Unlike healthy subjects, neither borderline nor avoidant personality disorder patients exhibited increased activity in the dorsal anterior cingulate cortex when viewing repeated versus novel pictures. This lack of an increase in dorsal anterior cingulate activity was associated with greater affective instability in borderline patients. In addition, borderline and avoidant patients exhibited smaller increases in insula-amygdala functional connectivity than healthy subjects and, unlike healthy subjects, did not show habituation in ratings of the emotional intensity of the images. Borderline patients differed from avoidant patients in insula-ventral anterior cingulate functional connectivity during habituation.Unlike healthy subjects, borderline patients fail to habituate to negative pictures, and they differ from both healthy subjects and avoidant patients in neural activity during habituation. A failure to effectively engage emotional habituation processes may contribute to affective instability in borderline patients.
Benefits of Tight Blood Pressure Control in Diabetic Patients With Hypertension
Authors: Gianfranco Parati, Grzegorz Bilo, Juan E. Ochoa
Journal: Diabetes Care (2011)

In 2008, when the UK Prospective Diabetes Study (UKPDS) group presented their 30-year findings concerning the possible sustained effects of improved glycemic control after 10 years of extended follow-up in type 2 diabetic patients, a so-called “legacy effect” was reported to address the long-term emergent and/or sustained benefits of early improved glycemic control. Opposite results were obtained by the Hypertension in Diabetes Study (HDS) carried out in the frame of UKPDS, with no evidence of any legacy effect on cardiovascular (CV) outcomes for an initial 4-year period of tight blood pressure (BP) control. Thus, it was concluded that BP control has to be continued over time, since, although it had a short time-to-effect relationship in preventing stroke, BP control was associated with a short persistence of its clinical benefits once the intervention was discontinued. These findings are unique because, whereas most interventional trials in hypertension that included diabetic patients have shown a reduction in CV outcomes shortly after starting treatment, only the UKPDS-HDS specifically explored the possible persistence of clinical benefits after discontinuing intensive BP-lowering intervention. This article aims to provide a critical interpretation of the UKPDS findings of lack of BP legacy, in the context of the currently available evidence on the benefits of antihypertensive treatment. The importance of effective BP control in type 2 diabetic patients to prevent CV outcomes and other diabetes-related complications is underlined, with emphasis on early, tight, and continuous BP control to optimize patients’ protection.
Ventricular Response in Atrial Fibrillation
Authors: RICHARD LANGENDORF, ALFRED PICK, LOUIS N. KATZ
Journal: Circulation (1965)

The ventricular response in atrial fibrillation is determined by the long refractory period of the AV junction. Since an atrial impulse is always available for transmission to the ventricles, a regular ventricular rhythm would be expected, the rate of which would reflect the duration of a stable junctional refractory phase. The irregularity of the ventricular action associated with atrial fibrillation, therefore, indicates changes of refractoriness of the AV junctional tissues from cycle to cycle. This can best be attributed to varying degrees of penetration of "blocked" atrial impulses into parts of the AV junction, and to the effect of such concealed conduction on the propagation of subsequent impulses. The following facts are pointed out and illustrated as evidence of concealed AV and VA conduction during atrial fibrillation: (a) Occurrence of a "compensatory pause" following a ventricular premature systole. (b) Failure of an AV nodal escape to appear at the expected time due to concealed discharge of a subsidiary AV nodal pacemaker by a penetrating atrial impulse. (c) Acceleration of the ventricular rate when atrial fibrillation changes to flutter (elimination of concealed conduction with slowing of the atria). (d) A tendency for two or more long cycles to occur in succession (each containing one or more concealed responses). The reasons for the variations of the refractory period at different levels of the AV junction as a result of concealed conduction are analyzed. Their complex interplay may readily account for the over-all irregularity of the ventricular response associated with atrial fibrillation.
Prescription Practices in the Treatment of First-Episode Schizophrenia Spectrum Disorders: Data From the National RAISE-ETP Study
Authors: Delbert G. Robinson, Nina R. Schooler, Majnu John, Christoph U. Correll, Patricia Marcy, Jean Addington, Mary F. Brunette, Sue E. Estroff, Kim T. Mueser, David Penn, James Robinson, Robert A. Rosenheck, Joanne Severe, Amy Goldstein, Susan Azrin, Robert Heinssen, John M. Kane
Journal: American Journal of Psychiatry (2014)

Treatment guidelines suggest distinctive medication strategies for first-episode and multiepisode patients with schizophrenia. To assess the extent to which community clinicians adjust their usual treatment regimens for first-episode patients, the authors examined prescription patterns and factors associated with prescription choice in a national cohort of early-phase patients.Prescription data at study entry were obtained from 404 participants in the Recovery After an Initial Schizophrenia Episode Project's Early Treatment Program (RAISE-ETP), a nationwide multisite effectiveness study for patients with first-episode schizophrenia spectrum disorders. Treatment with antipsychotics did not exceed 6 months at study entry.The authors identified 159 patients (39.4% of the sample) who might benefit from changes in their psychotropic prescriptions. Of these, 8.8% received prescriptions for recommended antipsychotics at higher than recommended dosages; 32.1% received prescriptions for olanzapine (often at high dosages), 23.3% for more than one antipsychotic, 36.5% for an antipsychotic and also an antidepressant without a clear indication, 10.1% for psychotropic medications without an antipsychotic, and 1.2% for stimulants. Multivariate analysis showed evidence for sex, age, and insurance status effects on prescription practices. Racial and ethnic effects consistent with effects reported in previous studies of multiepisode patients were found in univariate analyses. Despite some regional variations in prescription practices, no region consistently had different practices from the others. Diagnosis had limited and inconsistent effects.Besides prescriber education, policy makers may need to consider not only patient factors but also service delivery factors in efforts to improve prescription practices for first-episode schizophrenia patients.
Molecular Pathomechanisms of Membranous Nephropathy
Authors: Pierre Ronco, Hanna Debiec
Journal: Journal of the American Society of Nephrology (2005)

Membranous nephropathy (MN), the most common cause of idiopathic nephrotic syndrome in white adults, is characterized by an accumulation of immune deposits on the outer aspect of the glomerular basement membrane. In Heymann nephritis, the rat experimental model for MN, megalin--the target antigen of the nephritogenic antibodies--is expressed on the surface of podocytes, where immune complexes are formed, leading to complement activation and nephrotic-range proteinuria. However, megalin cannot be held responsible for human MN because it has not been found in human podocytes or detected in subepithelial immune deposits in patients with MN. Several potential antigens have been identified in so-called secondary forms of MN, but there is no real proof that these antigens are pathogenic. In a subgroup of infants with antenatal MN, neutral endopeptidase (NEP) has been identified as the first protein target on human podocytes of nephritogenic antibodies. The infants' mothers became immunized during pregnancy against NEP expressed on syncytiotrophoblastic cells because they were NEP deficient as a result of truncating mutations in the MME gene. Severity of neonatal renal disease was determined by the mothers' IgG response that led to the formation of the membrane attack complex of complement in the subepithelial deposits. Alloimmunization against NEP is a novel pathomechanism of MN that might also account for some cases of MN after renal or bone marrow transplantation. Other types of alloimmunization should be investigated in MN but also in other renal and nonrenal diseases, particularly those that affect the pediatric age.
Novel drugs against tuberculosis: a clinician's perspective
Authors: Ioana Diana Olaru, Florian von Groote-Bidlingmaier, Jan Heyckendorf, Wing Wai Yew, Christoph Lange, Kwok Chiu Chang
Journal: European Respiratory Journal (2014)

The United Nations Millennium Development Goal of reversing the global spread of tuberculosis by 2015 has been offset by the rampant re-emergence of drug-resistant tuberculosis, in particular fluoroquinolone-resistant multidrug-resistant and extensively drug-resistant tuberculosis. After decades of quiescence in the development of antituberculosis medications, bedaquiline and delamanid have been conditionally approved for the treatment of drug-resistant tuberculosis, while several other novel compounds (AZD5847, PA-824, SQ109 and sutezolid) have been evaluated in phase II clinical trials. Before novel drugs can find their place in the battle against drug-resistant tuberculosis, linezolid has been compassionately used with success in the treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis. This review largely discusses six novel drugs that have been evaluated in phase II and III clinical trials, with focus on the clinical evidence for efficacy and safety, potential drug interactions, and prospect for using multiple novel drugs in new regimens.
International Union of Pharmacology LVII: Recommendations for the Nomenclature of Receptors for Relaxin Family Peptides
Authors: Ross A. Bathgate, Richard Ivell, Barbara M. Sanborn, O. David Sherwood, Roger J. Summers
Journal: Pharmacological Reviews (2006)

Although the hormone relaxin was discovered 80 years ago, only in the past 5 years have the receptors for relaxin and three other receptors that respond to related peptides been identified with all four receptors being G-protein-coupled receptors. In this review it is suggested that the receptors for relaxin (LGR7) and those for the related peptides insulin-like peptide 3 (LGR8), relaxin-3 (GPCR135), and insulin-like peptide 5 (LGPCR142) be named the relaxin family peptide receptors 1 through 4 (RXFP1-4). RXFP1 and RXFP2 are leucine-rich repeat-containing G-protein-coupled receptors with complex binding characteristics involving both the large ectodomain and the transmembrane loops. RXFP1 activates adenylate cyclase, protein kinase A, protein kinase C, phosphatidylinositol 3-kinase, and extracellular signaling regulated kinase (Erk1/2) and also interacts with nitric oxide signaling. RXFP2 activates adenylate cyclase in recombinant systems, but physiological responses are sensitive to pertussis toxin. RXFP3 and RXFP4 resemble more conventional peptide liganded receptors and both inhibit adenylate cyclase, and in addition RXFP3 activates Erk1/2 signaling. Physiological studies and examination of the phenotypes of transgenic mice have established that relaxin has roles as a reproductive hormone involved in uterine relaxation (some species), reproductive tissue growth, and collagen remodeling but also in the cardiovascular and renal systems and in the brain. The connective tissue remodeling properties of relaxin acting at RXFP1 receptors have potential for the development of agents effective for the treatment of cardiac and renal fibrosis, asthma, and scleroderma and for orthodontic remodelling. Agents acting at RXFP2 receptors may be useful for the treatment of cryptorchidism and infertility, whereas antagonists may be used as contraceptives. The brain distribution of RXFP3 receptors suggests that actions at these receptors have the potential for the development of antianxiety and antiobesity drugs.
PTH-089 Impact of Seasonal Variation on Course of Inflammatory Bowel Disease and Effect of Date of Births on the Onset of Disease: A Fact or a Myth!
Authors: R Mahmood, J Slater, L Wood, M Anwar, H Muhammad, S Cooper, S DeSilva, S Shetty, N C Fisher, S Ishaq
Journal: Gut (2013)

<h3>Introduction</h3> Effect of seasonal variation on the natural history of the inflammatory bowel disease (IBD) is now well known. Also births in certain time of the year may have an impact on the onset of inflammatory bowel disease later in life. We reviewed our cohort with inflammatory bowel disease over the last four years to look for any such association. <h3>Methods</h3> Data collection was retrospective over the last 4 years using IBD database and medical records. Clinical and demographic details of newly diagnosed patients with IBD were recorded. <h3>Aims</h3> Our aim was to identify any evidence of seasonal variability on natural history of IBD and to identify any link between the onset of IBD symptoms and the date of births. <h3>Results</h3> We had 279 newly diagnosed cases of inflammatory bowel disease during the last 4 years (2008–2011). There was incremental rise in the incidence of disease during this period and majority of the cases had UC (70% UC, 30% CD). There was no consistent correlation of incidence of IBD in any particular season over the last four years <i>(p value</i> = 0.065). Furthermore, there was no consistency in the data for the birth dates pattern and the onset of disease symptoms in our cohort. <h3>Conclusion</h3> In our retrospective cohort study we could not demonstrate seasonal variability or impact of date of birth on disease onset but ongoing prospective data collection over a longer period of time may help explore this association. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Lewis JD, Aberra FN, Lichtenstein GR, Bilker WB, Brensinger C, Strom BL. Seasonal variation in flares of inflammatory bowel disease.Gastroenterology. 2004 Mar; 126(3):665–73. Haslam N, Mayberry JF, Hawthorne AB, Newcombe RG, Holmes GK, Probert CS. Measles, month of birth, and Crohn’s disease. Gut. 2000 Dec; 47(6):801–3.
Frequency and significance of tumor thrombi in esophageal varices in hepatocellular carcinoma associated with cirrhosis
Authors: Masahiro Arakawa, Masayoshi Kage, Shin-Ichi Matsumoto, Yasuhisa Akagi, Takemi Noda, Kazunori Fukuda, Toshiro Nakashima, Kunio Okuda
Journal: Hepatology (1986)

Histological examination of the wall of the stomach and esophagus in patients with hepatocellular carcinoma associated with cirrhosis demonstrated intravariceal tumor thrombi in 13 (23.6%) of 55 cases studied. There were distant hematogenous metastases in 31 of them, of whom 12 (38.7%) had variceal tumor thrombi. Tumor thrombi were of varying sizes, and tumor cells appeared either intact, degenerated or necrotic. In seven cases, there was a firm adhesion of thrombi onto the vascular wall suggesting possible mural infiltration, but no extravascular metastases were noted grossly. These findings suggest a possibility of metastasis of hepatocellular carcinoma to the stomach and esophagus via the portal vein. It is also suggested that the degree of varices is not increased by tumor thrombus formation per se, and that both varices and tumor thrombi are due to extensive hepatofugal collateral circulation. Considering that 12 of 13 cases of intravariceal tumor thrombi had lung metastases, a portal vein-varices-lung route is possible for lung metastasis beside the established route through the hepatic vein in hepatocellular carcinoma.
High and Low Gain Switches for Regulation of cAMP Efflux Concentration
Authors: Jin Fu Wen, Xun Cui, Jing Yu Jin, Soo Mi Kim, Sung Zoo Kim, Suhn Hee Kim, Ho Sub Lee, Kyung Woo Cho
Journal: Circulation Research (2004)

This study tests the hypothesis that particulate (p) guanylyl cyclase (GC) and soluble (s) GC are involved in the distinct roles for the regulation of cGMP-PDE-cAMP signaling and of mechanical and secretory functions in the heart. Experiments were performed in perfused beating rabbit atria. C-type natriuretic peptide (CNP) and SIN-1, an NO donor, or BAY 41-2272 (BAY), a direct activator for sGC, were used to activate pGC and sGC, respectively. CNP and SIN-1 increased cGMP and cAMP efflux in a concentration-dependent manner. Increase in cAMP was a function of cGMP. The changes in cAMP efflux concentration in terms of cGMP were much more prominent in the atria treated with CNP than in the atria treated with SIN-1. Increase in cAMP efflux concentration was blocked by milrinone but not changed by EHNA. BAY increased cGMP but not cAMP in a concentration-dependent manner. CNP and SIN-1 decreased atrial stroke volume and myocytic ANP release. The decreases in terms of cGMP efflux concentration were much more prominent in the atria treated with CNP than in the atria treated with SIN-1 or BAY. Milrinone accentuated GC agonist–induced decreases in atrial stroke volume and ANP release. In the presence of ODQ, SIN-1 or BAY induced effects were not observed. These data suggest that pGC and sGC activations have distinct roles via cGMP-PDE3-cAMP signaling in the cardiac atrium: high and low gain switches, respectively, for the regulation of cAMP levels and contractile and secretory functions.
Strategies to Manage the Adverse Effects of Oral Morphine: An Evidence-Based Report
Authors: Nathan Cherny, Carla Ripamonti, Jose Pereira, Carol Davis, Marie Fallon, Henry McQuay, Sebastiano Mercadante, Gavril Pasternak, Vittorio Ventafridda
Journal: Journal of Clinical Oncology (2001)

ABSTRACT: Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. By these criteria, a substantial minority of patients treated with oral morphine (10% to 30%) do not have a successful outcome because of (1) excessive adverse effects, (2) inadequate analgesia, or (3) a combination of both excessive adverse effects along with inadequate analgesia. The management of excessive adverse effects remains a major clinical challenge. Multiple approaches have been described to address this problem. The clinical challenge of selecting the best option is enhanced by the lack of definitive, evidence-based comparative data. Indeed, this aspect of opioid therapeutics has become a focus of substantial controversy. This study presents evidence-based recommendations for clinical-practice formulated by an Expert Working Group of the European Association of Palliative Care (EAPC) Research Network. These recommendations highlight the need for careful evaluation to distinguish between morphine adverse effects from comorbidity, dehydration, or drug interactions, and initial consideration of dose reduction (possibly by the addition of a co analgesic). If side effects persist, the clinician should consider options of symptomatic management of the adverse effect, opioid rotation, or switching route of systemic administration. The approaches are described and guidelines are provided to aid in selecting between therapeutic options.