tbuckley/cabot-search huggingface dataset:
Modulation of intrinsic cardiac neurons by spinal cord stimulation: implications for its therapeutic use in angina pectoris
Authors: R Foreman
Journal: Cardiovascular Research (2000)

Electrical stimulation of the dorsal aspect of the upper thoracic spinal cord is used increasingly to treat patients with severe angina pectoris refractory to conventional therapeutic strategies. Clinical studies show that spinal cord stimulation (SCS) is a safe adjunct therapy for cardiac patients, producing anti-anginal as well as anti-ischemic effects. However, little information is yet available about the underlying mechanisms involved.In order to determine its mechanism of action, the effects of SCS on the final common integrator of cardiac function, the intrinsic cardiac nervous system, was studied during basal states as well as during transient (2 min) myocardial ischemia. Activity generated by intrinsic cardiac neurons was recorded in 9 anesthetized dogs in the absence and presence of myocardial ischemia before, during and after stimulating the dorsal T1-T2 segments of the spinal cord at 66 and 90% of motor threshold using epidural bipolar electrodes (50 Hz; 0.2 ms; parameters within the therapeutic range used in humans).The SCS suppressed activity generated by intrinsic cardiac neurons. No concomitant change in monitored cardiovascular indices was detected. Neuronal activity increased during transient ventricular ischemia (46%), as well as during the early reperfusion period (68% compared to control). Despite that, activity was suppressed during both states by SCS.SCS modifies the capacity of intrinsic cardiac neurons to generate activity. SCS also acts to suppress the excitatory effects that local myocardial ischemia exerts on such neurons. Since no significant changes in monitored cardiovascular indices were observed during SCS, it is concluded that modulation of the intrinsic cardiac nervous system might contribute to the therapeutic effects of SCS in patients with angina pectoris.
Transesophageal pulmonary lobectomy with single transthoracic port assistance: study with survival assessment in a porcine model
Authors: J. Moreira-Pinto, A. Ferreira, A. Miranda, C. Rolanda, J. Correia-Pinto
Journal: Endoscopy (2012)

<b>Background and study aims:</b> Thoracoscopic pulmonary lobectomy is being performed in an increasing number of patients. The aims of the current study were to assess natural orifice transluminal endoscopic surgery (NOTES) as an alternative to transthoracic endoscopic surgery, and to test the feasibility of peroral transesophageal right upper pulmonary lobectomy with the assistance of a single transthoracic trocar. <b>Methods:</b> In 10 acute and 4 survival pigs, right upper pulmonary lobectomy was performed using a forward-viewing double-channel gastroscope and an operative thoracoscope with a 5-mm working channel inserted through a single transthoracic 12 – mm) port. Time, safety, and feasibility of the following steps were recorded in all animals: esophagotomy, hilar dissection, individual ligation of the hilum elements, pulmonary lobectomy, and specimen retrieval. In the survival experiments, esophagotomy was closed using a reticulated laparoscopy suture device and an esophageal stent was placed. These animals were kept alive and monitored for 2 weeks. <b>Results:</b> Esophagotomy was performed safely in all animals (mean procedure duration 5.4 ± 1.7 minutes). Dissection of the right upper lobe hilum elements (bronchus, arteries, and veins) was carried out without adverse events. Individual ligation of the hilum elements was performed in all but two cases (time for dissection and ligation 44.2 ± 14.8 minutes). Lobectomy and specimen retrieval were completed in all animals (9.5 ± 3.1 minutes). Esophagotomy closure and stent placement were carried out in 20.0 ± 2.8 minutes in the survival animals. These animals fed normally and gained weight postoperatively without signs of disease. Endoscopic examination before necropsy revealed a pseudo-diverticulum in one animal, and wound dehiscence with confined collection/recess in the remaining animals. <b>Conclusions:</b> Transesophageal right upper pulmonary lobectomy using single transthoracic trocar assistance is feasible and may represent a step towards scar-free pulmonary lobectomy.
Structural differences in airways during chronic rejection after lung transplantation: A (micro)-CT analysis
Authors: Stijn Verleden, Stijn Willems, David Ruttens, Robin Vos, John McDonough, Annemie Vaneylen, Erik Verbeken, Johny Verschakelen, Dirk Van Raemdonck, Benoït Rondelet, Christiane Knoop, Marc Decramer, James Hogg, Geert Verleden, Bart Vanaudenaerde
Journal: European Respiratory Journal (2012)

Chronic rejection is a major problem after lung transplantation (Tx) and is accepted to be a small airway disease. Recently a distinction between an obstructive (fBOS) and restrictive phenotype (RAS) has been made. We aimed to investigate structural differences.  Human explant lungs from 5 fBOS and 3 RAS patients were collected during reTx, were air-inflated to TLC, frozen solid in liquid nitrogen vapor and frozen specimens were examined by HRCT. Unused donor lung (n=1) served as control. The lungs were kept frozen while cut in 2cm slices and cylinders of 1.4cm diameter were removed. These were fixed at -20°C in a solution of acetone/1% gluteraldehyde and warmed to 25°C, dried and scanned with microCT (skyscan1172, Belgium).  HRCT images showed that RAS lungs displayed a lower number of airways starting at generation 5. In patients with fBOS >50% of the airways get obstructed at generation 6 (figure 1), mainly in airways   In conclusion: in RAS lungs, both airways>1mm and terminal bronchioles shrink and/or disappear while in fBOS lungs, the airways become obstructed. There was no difference in terminal bronchioles between fBOS and normal lung.
THE APPLICATION OF FERRITIN-CONJUGATED ANTIBODY TO ELECTRON MICROSCOPIC STUDIES OF INFLUENZA VIRUS IN INFECTED CELLS
Authors: Councilman Morgan, Konrad C. Hsu, Richard A. Rifkind, Alice W. Knox, Harry M. Rose
Journal: The Journal of Experimental Medicine (1961)

Immersion of chorioallantoic membranes infected by influenza virus in ferritin-conjugated antibody globulin prior to fixation permits recognition of viral antigen at the cellular surface. In some cases the antigen is confined to sites at which viral particles appear to be in process of release, whereas in others it is present along the entire cellular surface. During infection part or all of the cellular membrane presumably is transformed so that it contains the antigenic and structural components which coat the virus during emergence. It is suggested that detached fragments of cytoplasm possessing surface hemagglutinin but incapable of initiating infection constitute at least one form of "incomplete virus."
Regulation: the art of control? Regulatory T cells and asthma and allergy
Authors: D S Robinson
Journal: Thorax (2004)

A better understanding of the immunology of regulation may allow preventive or disease modifying treatment for asthma and other respiratory diseases

Much is currently made of the control of asthma in therapeutic guidelines. Both the British guidelines and the Global Initiative for Asthma (GINA) define measures of control of the disease, and recent studies have defined strategies for control using available anti-inflammatory and bronchodilator therapy such as inhaled steroids and long acting β2 agonists.1,2 However, currently available treatments suppress inflammation but do not modify the underlying immunological predisposition to the disease.

Asthma is widely recognised as an inflammatory airway disease driven by activation of Th2-type T lymphocytes in both atopic allergic and intrinsic or non-allergic forms.3–5 Recent advances in our understanding of the control of the immunological process have identified regulatory suppressive T cells which can prevent activation of self-reactive or pathological T cells in autoimmune or infectious disease models.6–8 Does this understanding of immune regulation hold the prospect of disease control or even prevention for asthma?

The interest of immunologists in actively suppressive T cells was re-awoken by the finding by Sakaguchi and co-workers that depletion of CD4+CD25+ T lymphocytes from mice led to development of autoimmune pathology which could be prevented by re-introduction of these cells.9 Such CD4+CD25+ regulatory T cells were active in many disease models and could reverse established inflammatory diseases such as colitis.10 These cells were shown to arise by high affinity selection in the thymus and are thought to form a “naturally occurring” regulatory population that is an important part of maintenance of tolerance or non-reactivity of the immune system against itself.11,12 Shevach and co-workers established an in vitro system and showed that CD4+CD25+ T cells failed to proliferate to polyclonal or antigenic …
Ciliary Body Endophotocoagulation during Pars Plana Vitrectomy in Eyes with Vitreoretinal Disorders and Concomitant Uncontrolled Glaucoma
Authors: Jennifer I. Lim, Michael Lynn, Antonio Capone, Thomas M. Aaberg, Daniel F. Martin, Carolyn Drews-Botsch
Journal: Ophthalmology (1996)
Miss, Mister, Doctor: My surgeon's name is...
Authors: J. Scurr
Journal: Journal of the Royal Society of Medicine (2006)

How we are titled is of little consequence I found the editorial (April 2006 JRSM 1 ) on how we are titled most interesting.This is a continuation of the debate that the dental profession has been having for many years, fuelled by both an influx of overseas graduates styling themselves as 'Doctor', and by the development of the role of dentists from 'toothwrights' to practitioners with a more holistic approach encompassing the oral health and wellbeing of those in their care.However all of us, physicians, surgeons, general practitioners and dentists have one thing in commonpatients.But that may be about to change.The same week as the editorial appeared, the chief executive of the Sussex Partnership NHS Trust ordered staff not to refer to people receiving medical care as patients but as clients.This not only demonstrates a misunderstanding of our roles but also devalues both practitioners and those that we care for.Patients are not simply clients or users of health services.Patients are those receiving care, who are given time, are listened to and treated with sympathy, understanding and expertise.There is something special about the term patient, and although to give a precise dictionary definition is difficult, it is well understood by those who deliver the care.How we are titled may well, as the editorial states, be of little consequence; far more important is how we refer to, and perceive, those in our care.
β-Arrestin-1 Levels: Reduced in Leukocytes of Patients With Depression and Elevated by Antidepressants in Rat Brain
Authors: Sofia Avissar, Angela Matuzany-Ruban, Keren Tzukert, Gabriel Schreiber
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: β-Arrestins play a pivotal role in G protein-coupled receptor desensitization. β-Arrestins interfere in G protein receptor interaction, thus leading to desensitization of G protein-mediated receptor signaling. G protein receptor signaling and its desensitization were previously implicated in the pathophysiology of mood disorders and in the mechanism of action of antidepressant and mood-stabilizing treatments. The present study aims at quantitatively evaluating β-arrestin-1 levels in leukocytes of patients with major depression and the effect of antidepressants on β-arrestin-1 levels in rat brain. METHOD: β-arrestin-1 measurements were carried out in cortical, hippocampal, and striatal brain regions of rats chronically intragastrically treated with either imipramine, desipramine, or fluvoxamine. Similar measurements were conducted in mononuclear leukocytes of 36 untreated patients with major depression and 32 healthy volunteer subjects. β-Arrestin-1 levels were evaluated through immunoblot analyses using monoclonal antibodies to β-arrestin-1. RESULTS: β-Arrestin-1 levels were significantly elevated by all three antidepressants in rat cortex and hippocampus, while in the striatum no alterations could be detected. This process became significant within 10 days and took 2–3 weeks to reach maximal increase. Mononuclear leukocytes of patients with depression showed significantly reduced immunoreactive quantities of β-arrestin-1. The reduction in β-arrestin-1 levels was significantly correlated with the severity of depressive symptoms. CONCLUSIONS: The findings in the rat study suggest β-arrestin-1 elevation as a biochemical mechanism for antidepressant-induced receptor down-regulation. The findings in human subjects support the implication of β-arrestin-1 in the pathophysiology of mood disorders. β-Arrestin-1 measurements in patients with depression may potentially serve as a biochemical marker for depression.
The microbiota-gut-brain axis: learning from intestinal bacteria?
Authors: P. Bercik
Journal: Gut (2011)

The intestinal microbiota is a diverse and dynamic ecosystem,1 which has developed a mutualistic relationship with its host and plays a crucial role in the development of the host's innate and adaptive immune responses.2 This ecosystem serves the host by protecting against pathogens, harvesting otherwise inaccessible nutrients, aiding in neutralisation of drugs and carcinogens, and affecting the metabolism of lipids.3 Gut bacteria modulate intestinal motility, barrier function and visceral perception.4

An interaction between the intestinal microbiota and the central nervous system (CNS) may seem difficult to conceive at first sight, but clinicians are well aware of the benefit of oral antibiotics and laxatives in the treatment of hepatic encephalopathy.5 Data accumulated from animal studies indicate that there is central sensing of gastrointestinal infections. For example, acute infection with Campylobacter jejuni results in anxiety-like behaviour and rapid activation of vagal pathways prior to onset of immune responses,6 while chronic Helicobacter pylori infection in mice leads to abnormal feeding behaviour and upregulation of tumour necrosis factor α (TNFα) in the median eminence of the hypothalamus.7 Rapid and sustained gut–brain communication may confer a significant advantage to the host, as central activation in response to changes in commensals or pathogens would allow better control of gut function and immunity.

How does the intestinal microbiota …
Effect of Intact Parathyroid Hormone on Hepatic Glucose Release in the Dog
Authors: Keith A. Hruska, Joan Blondin, Raymond Bass, Julio Santiago, Lorraine Thomas, Paul Altsheler, Kevin Martin, Saulo Klahr
Journal: Journal of Clinical Investigation (1979)

The liver has been shown to remove parathyroid hormone (PTH) from its arterial circulation by a mechanism that is selective for the intact form of the peptide (PTH 1-84). The present studies demonstrate that PTH has biologic effects on the liver in vivo. Bovine PTH 1-84 stimulated hepatic glucose release in dogs with indwelling hepatic vein catheters from basal values of 31±8 to 68±9 mg/min per kg after bolus injections of PTH. The effect on hepatic glucose release was apparent by 5 min and persisted for the 80 min of observation. The NH2-terminal PTH fragment (syn b-PTH 1-34) had no effect. Bovine PTH 1-84 administered in doses designed to produce circulating levels of immunoreactive PTH similar to the endogenous levels observed in uremic dogs also increased the incorporation of 14C from infused [14C]alanine into glucose, and increased estimated hepatic uptake of both chemical and [14C]alanine, while increasing hepatic glucose release. Thus, administration of “physiologic levels” of b-PTH 1-84 stimulated hepatic glucose release in part through increased gluconeogenesis in vivo, whereas syn b-PTH 1-34 had no demonstrable effect. Circulating levels of insulin rose after PTH administration, an increase which presumably represents a secondary response to the rise in glucose release.
COMPLEMENT-DEPENDENT RELEASE OF IMMUNE COMPLEXES FROM THE LYMPHOCYTE MEMBRANE
Authors: Gary W. Miller, Paul H. Saluk, Victor Nussenzweig
Journal: The Journal of Experimental Medicine (1973)

Soluble antigen-antibody-complement complexes bound to mouse B lymphocytes are rapidly released from the cell membrane in the presence of normal serum from several mammalian species. The release is not the result of antigen-antibody dissociation or extensive degradation of the complexes. However, the released complexes have been altered because they will no longer bind to fresh lymphocytes. The release is not the result of lymphocyte damage mediated by complement. It is complement-dependent, and is generated either preferentially or exclusively via the alternate pathway, since it occurs in C4-deficient serum, is Mg++ but not Ca++ dependent, and requires C3 proactivator. C3 inactivator is not involved. The release activity of the serum, once generated, is unstable at 37°C. The release of complexes from the lymphocyte membrane by serum provides a convenient assay for the functioning of the alternate pathway in the mouse and in other species.
Standard assessments of frailty are validated predictors of mortality in hospitalized patients with cirrhosis
Authors: Elliot B. Tapper, Daniel Finkelstein, Murray A. Mittleman, Gail Piatkowski, Michelle Lai
Journal: Hepatology (2015)

The risk of morbidity and mortality for hospitalized patients with cirrhosis is high and incompletely captured by conventional indices. We sought to evaluate the predictive role of frailty in an observational cohort study of inpatients with decompensated cirrhosis between 2010 and 2013. The primary outcome was 90‐day mortality. Secondary outcomes included discharge to a rehabilitation hospital, 30‐day readmission, and length of stay. Frailty was assessed with three metrics: activities of daily living (ADL), the Braden Scale, and the Morse fall risk score. A predictive model was validated by randomly dividing the population into training and validation cohorts: 734 patients were admitted 1358 times in the study period. The overall 90‐day mortality was 18.3%. The 30‐day readmission rate was 26.6%, and the rate of discharge to a rehabilitation facility was 14.3%. Adjusting for sex, age, Model for End‐Stage Liver Disease, sodium, and Charlson index, the odds ratio for the effect of an ADL score of less than 12 of 15 on mortality is 1.83 (95% confidence interval [CI] 1.05‐3.20). A predictive model for 90‐day mortality including ADL and Braden Scale yielded C statistics of 0.83 (95% CI 0.80‐0.86) and 0.77 (95% CI 0.71‐0.83) in the derivation and validation cohorts, respectively. Discharge to a rehabilitation hospital is predicted by both the ADL (&lt;12) and Braden Scale (&lt;16), with respective adjusted odds ratios of 3.78 (95% CI 1.97‐7.29) and 6.23 (95% CI 2.53‐15.4). Length of stay was associated with the Braden Scale (&lt;16) (hazard ratio = 0.63, 95% CI 0.44‐0.91). No frailty measure was associated with 30‐day readmission. Conclusions : Readily available, standardized measures of frailty predict 90‐day mortality, length of stay, and rehabilitation needs for hospitalized patients with cirrhosis. (H epatology 2015;62:584–590
Population-Based, Multigenerational Family Clustering Study of Obsessive-compulsive Disorder
Authors: David Mataix-Cols, Marcus Boman, Benedetta Monzani, Christian Rück, Eva Serlachius, Niklas Långström, Paul Lichtenstein
Journal: JAMA Psychiatry (2013)

Controlled family studies have consistently found that obsessive-compulsive disorder (OCD) aggregates in families but have typically relied on samples recruited from specialist clinics. Furthermore, previous studies could not disentangle genetic from environmental factors contributing to the observed familiality.To provide unbiased estimates of familial risk for and heritability of OCD at the population level.Population-based, multigenerational, case-control family and twin studies using the Swedish National Patient Register, Multi-Generation Register, and Twin Register.All individuals diagnosed as having OCD between January 1, 1969, and December 31, 2009 (n = 24 768) and all their available first-, second-, and third-degree relatives, as well as nonbiological relatives and matched general population control subjects. Twins (n = 16 383) were included from the population-based Twin Register.The risk for OCD among relatives of OCD probands.The risk for OCD among relatives of OCD probands increased proportionally to the degree of genetic relatedness. The risk for first-degree relatives was significantly higher than that for second- and third-degree and nonbiological relatives. Second-degree relatives had higher risk for OCD than third-degree relatives. Relatives at similar genetic distances had similar risks for OCD, despite different degrees of shared environment. Separate twin modeling analyses confirmed that familial risk for OCD was largely attributable to additive genetic factors (47%; 95% CI, 42%-52%), with no significant effect of shared environment. Nonbiological relatives (spouses or partners who have at least 1 child together) also had an elevated risk for OCD (odds ratio, 2.61; 95% CI, 1.99-3.42). Early-onset probands (3907 individuals; mean age, 13.7 years) had slightly (nonsignificantly) higher familial risk than the total sample, although this was substantially lower than previously reported. There were no significant sex differences in the familial pattern or heritability estimates.Obsessive-compulsive disorder clusters in families primarily due to genetic factors. Nonshared environmental factors are at least as important. The quest for candidate genes, nonshared environmental risk factors, and their possible correlation or interaction should continue. The finding of possible assortative mating in OCD is intriguing and should be investigated further.
Current Concepts in AIDS Pathogenesis: Insights from the SIV/Macaque Model
Authors: Andrew A. Lackner, Ronald S. Veazey
Journal: Annual Review of Medicine (2007)

The pathogenesis of AIDS has proven to be quite complex and dynamic, with most of the critical events (e.g., transmission, CD4(+) T cell destruction) occurring in tissues that are not easily accessible for analysis. In addition, although the disease can progress over years, many critical events happen within the first few weeks of infection, when most patients are unaware that they are infected. The nonhuman primate model of AIDS has been used extensively to fill these gaps in our understanding of AIDS pathogenesis.