tbuckley/cabot-search huggingface dataset:
Cytosolic Phospholipase A2 Plays a Key Role in the Pathogenesis of Multiple Sclerosis-like Disease
Authors: Athena Kalyvas, Samuel David
Journal: Neuron (2004)

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) that results in motor and sensory deficits. Although MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are thought to be T cell-mediated diseases, the mechanisms underlying the lesions in the CNS are not fully understood. We propose that a strong candidate as a central mediator in evoking the complex pathological changes seen in MS and EAE is the enzyme cytosolic phospholipase A2 (cPLA2). One of the metabolic products of this enzyme is pro-inflammatory, while the other induces myelin breakdown, demyelination, and chemokine/cytokine expression. We provide evidence that cPLA2 is highly expressed in EAE lesions and show that blocking this enzyme leads to a remarkable reduction in the onset and progression of EAE.
THE INTRAVENOUS INJECTION OF MAGNESIUM SULPHATE FOR ANESTHESIA IN ANIMALS
Authors: J. Auer, S. J. Meltzer
Journal: The Journal of Experimental Medicine (1916)

These experiments justify the following general conclusions. By the intravenous injection of M/4 magnesium sulphate into dogs at a certain rate, a stage can be reached where the abdominal walls are completely relaxed and when section of the abdomen and stimulation of sensitive parts of the parietal peritoneum do not produce pain or elicit any reaction of the animal. At the same time spontaneous respiration may still be maintained within normal limits and the lid reflex be fair or even normal. In this stage intratracheal intubation for artificial respiration can be easily accomplished. This stage may be attained in 12 to 14 minutes when the rate of injection is about 3 cc. per minute. When this stage is once attained the rate of injection should gradually be reduced, otherwise, sooner or later, spontaneous respiration will be abolished, and by a further maintenance of the rate of injection all the skeletal muscles may become paralyzed. When the injection of magnesium is continued for a longer period, the paralytic effects of the magnesium injection will set in, even when administered at a slow rate. The paralysis of the respiratory function is readily met by intrapharyngeal insufflation, which is easily executed even without training in this procedure, or by the method of intratracheal insufflation, if executed by one trained in its management. When the respiration of the animal is accomplished by insufflation, the paralytic effect of the magnesium may be abolished fairly rapidly by an intravenous injection of about 10 cc. of an M/8 calcium chloride solution; or it may disappear slowly, after the infusion of the magnesium solution is discontinued for some time. The latter mode of disappearance may be favorably accelerated by an intravenous infusion of 60 to 100 cc. of an M/4 solution of sodium sulphate. The production of anesthesia by intravenous injection of magnesium sulphate should not be undertaken unless an apparatus for intrapharyngeal insufflation is at hand, because in exceptional cases the disappearance of spontaneous respiration may be one of the earliest consequences of the magnesium injection. The injection of calcium chloride should not be employed in cases in which the subject shows cardiac insufficiency. In such instances, moreover, injections of magnesium should not be used for the purpose of anesthesia; at least not until greater experience has been acquired in the employment of this method.
Multiple individual and cross-specific indiotypes on 13 levan-binding myeloma proteins of BALB/c mice.
Authors: R Lieberman, M Potter, W Humphrey, E B Mushinski, M Vrana
Journal: The Journal of Experimental Medicine (1975)

13 leven-binding myeloma proteins (LBMP) of BALB/c origin were classified into two groups with different binding specificities; one group of 11 proteins bound beta2 leads to 1 fructosans, a second group of two proteins bound fructosans probably of beta2 leads to 6 linkage. Anti-idiotypic sera prepared to 10 of the proteins in the appropriate strains of mice identified numerous idiotypic determinants. Each protein used for immunization had its own unique individual idiotypic specificities (IdI) and in addition most of the proteins carried two-nine cross-specific or shared idiotypes (IdX) that were found only among LBMP, and not found in 106 non-LBMP. Most of the IdX determinants and only four of the IdI determinants of the beta2 leads to 1 fructosan binding group were located in the antigen-binding site. The multiplicity of antigenic differences in this functionally related group of immunoglobulins reveals an unexpected degree of heterogeneity in V-regions that appears to be unrelated to binding.
Association of Family History With Cancer Recurrence and Survival in Patients With Gastric Cancer
Authors: Mi Ah Han, Myueng Guen Oh, Il Ju Choi, Sook Ryun Park, Keun Won Ryu, Byung-Ho Nam, Soo-Jeong Cho, Chan Gyoo Kim, Jun Ho Lee, Young-Woo Kim
Journal: Journal of Clinical Oncology (2012)

Family history of gastric cancer is a major risk factor for the disease. In this study, we investigated the prognoses of patients with gastric cancer with a family history.We retrospectively reviewed data from 1,273 patients with gastric adenocarcinoma who had undergone gastrectomy between 2001 and 2005 at a tertiary cancer center hospital. A positive family history was defined as a self-reported history of cancer in first- or second-degree relatives. Patients were followed up until December 2009 for death or recurrence. Clinicopathologic characteristics were compared by family history. Kaplan-Meier plots and Cox proportional hazards regressions were applied for disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS).Of 1,273 patients, 263 patients (20.6%) had first-degree relatives with a history of gastric cancer. First-degree family history of gastric cancer was associated with better DFS, RFS, and OS (P = .012, .006, and .005, respectively). In patients with stage I or II gastric cancer, first-degree family history was not associated with survival. However, it was associated with a reduced risk of recurrence or mortality in patients with stage III or IV gastric cancer. Compared with patients without a family history, the adjusted hazard ratios for those with a first-degree family history of gastric cancer were 0.49 (95% CI, 0.29 to 0.84) for DFS, 0.51 (95% CI, 0.30 to 0.87) for RFS, and 0.47 (95% CI, 0.26 to 0.84) for OS in patients with stage III or IV gastric cancer.A first-degree family history of gastric cancer is associated with improved survival after curative-intent surgery in patients with stage III or IV gastric cancer.
Feasibility and Compliance of Automated Measurement of Quality of Life in Oncology Practice
Authors: E.P. Wright, P.J. Selby, M. Crawford, A. Gillibrand, C. Johnston, T.J. Perren, R. Rush, A. Smith, G. Velikova, K. Watson, A. Gould, A. Cull
Journal: Journal of Clinical Oncology (2003)

Systematic quality-of-life (QOL) assessment may have value in oncology practice by increasing awareness of a wide range of issues, possibly increasing detection of psychologic morbidity, social problems, and changes in physical status, and improving care and its outcomes. However, logistic problems are substantial. Automated systems solve many of these problems. We field-tested the feasibility and compliance that can be achieved using a computer touchscreen system in two consecutive studies.In study 1, a prospective cohort of 272 patients was offered QOL assessment at each clinic appointment for 6 months. In study 2, all patients (N = 1,291) were offered QOL assessment as part of clinic routine during a 12-week period.In study 1, 82% of patients agreed to take part, but over time, compliance was poor (median, 40%; mean, 43%) and deteriorated with longer follow-up. In study 2, the overall compliance was greatly increased (median, 100%; mean, 70%), and compliance was retained over multiple visits. In study 1, compliance was better in younger patients, males, and socially advantaged patients, but was not affected by the presence of depression or anxiety, or QOL. In the second study, building on experience in the first study, data collection and storage in the computer system was excellent, achieving 98% of collected data stored in one center. In general, patients were comfortable with the computers and the approach. Data collection on the wards was more difficult and less complete than in clinics, especially for patients undergoing acute admissions.Feasibility with higher compliance was demonstrated in study 2, in which the data collection was integrated into routine care, and can be improved with further technical initiatives and education of staff.
Adrenergic Mechanisms in the Effects of Histamine in the Pulmonary Circulation of the Cat
Authors: H. J. H. COLEBATCH
Journal: Circulation Research (1970)

Histamine constricts airways and pulmonary blood vessels in isolated lungs, but is said to dilate pulmonary blood vessels in intact animals. The present experiments test the hypothesis that histamine only constricts pulmonary blood vessels, and that dilatation depends on epinephrine released by histamine from the adrenal glands. In cats anesthetized with pentobarbital, the difference in pressure between the pulmonary artery (PA) and left atrium (LA) was related to pulmonary blood flow measured by dye dilution before, and at intervals of 0.5 to 2 minutes after PA injection of histamine. In intact or vagotomized cats histamine increased PA-LA pressure difference and pulmonary blood flow, but calculated pulmonary vascular resistance (PVR) decreased significantly at 1 minute; control values were restored in 4 minutes. In adrenalectomized cats, histamine (10 to 40 µg) increased PA-LA pressure and PVR, but did not change pulmonary blood flow. After beta-receptor blockade with propranolol, histamine (10 to 20 µg) had the same effect as in adrenalectomized cats. After adrenalectomy or propranolol, the histamine-induced increase in PVR was prolonged. When histamine had increased PVR in adrenalectomized cats, epinephrine (5 µg iv) reduced PA-LA pressure and PVR. Histamine infusion (5 µg/kg/min iv) decreased PVR in intact cats, increased PVR in adrenalectomized cats, and when epinephrine (5 µ/kg/min) was also infused, decreased PVR in adrenalectomized cats. The results support the proposed hypothesis. Release of histamine locally in the lungs may encourage distribution of both blood and gas flows away from damaged and toward normal respiratory tissue.
Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): a randomised, open-label, phase 3 trial
Authors: Manfred Westphal, Seppo Ylä-Herttuala, John Martin, Peter Warnke, Philippe Menei, David Eckland, Judith Kinley, Richard Kay, Zvi Ram
Journal: The Lancet Oncology (2013)
Accelerated Calcium Nephrolithiasis
Authors: Fredric L. Coe
Journal: JAMA (1980)

Of 674 patients with calcium nephrolithiasis, 78 formed their stones in large numbers (average, 22 stones per patient) and at an accelerated rate (average, 172 stones per 100 patient-years). Although their stone disease was unusually severe, these patients had the common metabolic causes of stones and responded well to treatment. Patients with even the most extremely active calcium nephrolithiasis should be evaluated and managed in the same way as those with the common, less active form of the disease. (<i>JAMA</i>244:809-810, 1980)
Pre-existent left atrial scarring in patients undergoing pulmonary vein antrum isolation
Authors: Atul Verma, Oussama M. Wazni, Nassir F. Marrouche, David O. Martin, Fethi Kilicaslan, Stephen Minor, Robert A. Schweikert, Walid Saliba, Jennifer Cummings, J. David Burkhardt, Mandeep Bhargava, William A. Belden, Ahmad Abdul-Karim, Andrea Natale
Journal: Journal of the American College of Cardiology (2005)
Efficacy of retrowalking on strength and balance in patients with hamstring strain
Authors: Sami S Alabdelwahab, Shaji John
Journal: British Journal of Sports Medicine (2010)

Background Hamstring muscle strain is one of the most common injuries in sports. Retrowalking on treadmill is a common tool for lower extremity rehabilitation in the clinical settings. However, minimal clinical research has been conducted on the effectiveness of retrowalking on hamstring strain rehabilitation. Hypothesis: (1) Hamstring strain patients may show improved lower extremity strength and balance when trained with retrowalking. (2) The longer duration of retrowalking will show significant improvement as compared to shorter duration training. Study design Randomised control trial. Methodology 45 subjects all with hamstring strain were prospectively included in the study, all subjects were examined clinically for hamstring injury, and they were randomly assigned into three groups (groups A, B and C) of 15 subjects each. All the subjects were tested for strength and balance (static and dynamic) prior to and after the training. The hamstring muscle of all the participants in all the three groups were treated with moist heat and followed by passive stretching. Groups A and B also received 20 and 10 min of retrowalking, respectively. The total duration of the study was 3 weeks; all the treatments were administered four times a week for a total of 12 sessions, all the outcomes were measured pre-treatment at baseline and post-treatment after 1st, 2nd and 3rd weeks. Results The change in the determinants of quadriceps and ankle plantar flexors strength was significantly greater in the group which performed retrowalking for 20 min. Balance improved significantly in all groups except control group, but the most significant changes were seen in group A. Conclusions The result of this study suggests that the lower extremity strength and balance were improved with retrowalking and the longer duration of training led to most significant improvement. Clinical relevance The retrowalking can be incorporated as a safe method of lower extremity rehabilitation in hamstring strain patients.
Dual Serotonergic Regulation of Ventricular Contractile Force Through 5-HT <sub>2A</sub> and 5-HT <sub>4</sub> Receptors Induced in the Acute Failing Heart
Authors: Eirik Qvigstad, Ivar Sjaastad, Trond Brattelid, Caroline Nunn, Fredrik Swift, Jon Arne Kro Birkeland, Kurt A. Krobert, Geir Øystein Andersen, Ole M. Sejersted, Jan-Bjørn Osnes, Finn Olav Levy, Tor Skomedal
Journal: Circulation Research (2005)

Cardiac responsiveness to neurohumoral stimulation is altered in congestive heart failure (CHF). In chronic CHF, the left ventricle has become sensitive to serotonin because of appearance of G s -coupled 5-HT 4 receptors. Whether this also occurs in acute CHF is unknown. Serotonin responsiveness may develop gradually or represent an early response to the insult. Furthermore, serotonin receptor expression could vary with progression of the disease. Postinfarction CHF was induced in male Wistar rats by coronary artery ligation with nonligated sham-operated rats as control. Contractility was measured in left ventricular papillary muscles and mRNA quantified by real-time reverse-transcription PCR. Myosin light chain-2 phosphorylation was determined by charged gel electrophoresis and Western blotting. Ca 2+ transients in CHF were measured in field stimulated fluo-4-loaded cardiomyocytes. A novel 5-HT 2A receptor-mediated inotropic response was detected in acute failing ventricle, accompanied by increased 5-HT 2A mRNA levels. Functionally, this receptor dominated over 5-HT 4 receptors that were also induced. The 5-HT 2A receptor-mediated inotropic response displayed a triphasic pattern, shaped by temporally different activation of Ca 2+ -calmodulin-dependent myosin light chain kinase, Rho-associated kinase and inhibitory protein kinase C, and was accompanied by increased myosin light chain-2 phosphorylation. Ca 2+ transients were slightly decreased by 5-HT 2A stimulation. The acute failing rat ventricle is, thus, dually regulated by serotonin through G q -coupled 5-HT 2A receptors and G s -coupled 5-HT 4 receptors.
Collagen synthesis in fibroblasts from human colon: regulatory aspects and differences with skin fibroblasts.
Authors: M F Martens, C M Huyben, T Hendriks
Journal: Gut (1992)

The body wall muscles in Drosophila larvae are suitable for voltage clamp analysis of changes in membrane excitability caused by mutations. Both inward and outward ionic currents are present in these muscle fibers. The inward current is mediated by voltage-dependent Ca2+ channels. In Ca2+-free saline, the inward current is eliminated. The remaining outward K+ currents consist of two distinct components, an early transient IA and a delayed steady IK, which are separable by differences in the rate and voltage dependence of activation and inactivation. The steady-state and kinetic properties of the activation and inactivation processes of these two currents are analyzed. The results provide a basis for quantitative analysis of altered membrane currents in behavioral mutants of Drosophila. Previous studies indicate that mutations in the Shaker (Sh) locus alter excitability in both nerve and muscle in Drosophila. Our results support the idea that the channels mediating IA are molecularly distinct from those mediating IK. All Sh mutations studied specifically affect IA without changing the properties of the calcium current and IK. In certain alleles (ShKS133, Sh102, and ShM) IA is eliminated, permitting detailed studies of IK in isolation of IA. Studies of the alleles that do not eliminate IA provide additional information of the channels. In one such allele, Sh5, voltage dependence of IA activation is shifted to more positive potentials. This is accompanied by a less pronounced shift in the voltage dependence of inactivation. These results suggest that Sh5 mutation affects the voltage-sensitive mechanism of both activation and inactivation processes and that these two processes are not controlled by independent parts of the channel. Furthermore, the differential effects of these alleles on different excitable membranes imply that other genes take part in the control of IA. The effects of Sh5 on muscle depend on developmental stage. In larval muscle, Sh5 reduces the amplitude of IA because of the shift in the current-voltage (I-V) relation. In contrast, in adult Sh5 muscles, IA is reported to be normal in amplitude but shows abnormally rapid inactivation (Salkoff, L., and R. Wyman (1981) Nature 293: 228–230). A different allele, ShrK0120, causes a clear defect in nerve excitability, but analysis of IA in ShrK0120 larval muscle reveals I-V relations, inactivation, and recovery from inactivation similar to those seen in normal fibers. We suggest a possible mechanism of combinations of multiple interacting genes participating in the control of potassium channels to account for the presence of a variety of potassium channels in different excitable membranes.
Cardiac Contractility Is Not Depressed in Early Canine Endotoxic Shock
Authors: MICHAEL R. PINSKY, PHILLIPE RICO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We investigated effects of acute endotoxemia (Escherichia coli endotoxin, 1 mg/kg, intravenously) on left ventricular (LV) function in the first 4 h after induction of endotoxic shock in anesthetized canine preparations (n = 7 each, endotoxin and control groups). LV pressure and conductance (volume) catheters were used to construct pressure-volume loops. Transient inferior vena cava occlusion was used to rapidly and reversibly alter LV end-diastolic volume. LV contractility was assessed from the slope of the LV end-systolic pressure-volume relationship (Ees) and from preload-recruitable stroke work (PRSW), and from their change (DeltaEes and DeltaPRSW, respectively, measured at 2 and 4 h only), in response to a dobutamine infusion (5 microg/kg/min). Diastolic function and arterial tone were assessed as the maximal negative change in filling pressure versus time (max -dP/dt), filling rate, and arterial elastance (Ea), respectively. Ees, PRSW, Ea, diastolic function, and hemodynamics were measured hourly. Endotoxemia induced an immediate hypotensive, hyperdynamic, tachycardic state with progressive lactic acidosis. By 2.5 h after endotoxin infusion, heart rate returned to preendotoxin and control levels, but the other changes remained. However, no change occurred in LV Ees, DeltaEes, PRSW, DeltaPRSW, diastolic function, or Ea during the 4-h measurement interval. The cardiovascular collapse seen during the first 4 h of endotoxemia is therefore not due even partly to alterations in LV contractility.
Randomized Double-blind, Active-controlled Phase 3 Study to Assess 12-Month Safety and Efficacy of Mirabegron, a β3-Adrenoceptor Agonist, in Overactive Bladder
Authors: Christopher R. Chapple, Steven A. Kaplan, David Mitcheson, Jiri Klecka, Jana Cummings, Ted Drogendijk, Caroline Dorrepaal, Nancy Martin
Journal: European Urology (2012)
Primary care management of chronic cough
Authors: Rachel Harding, Sarah Chamberlain, Swapna Mandal, Nicholas Hart, Rachel Garrod, Surinder Birring
Journal: European Respiratory Journal (2013)

Introduction; The management of chronic cough in primary care is poorly understood. A better understanding may facilitate more effective management, by reducing the number of referrals to secondary care. We carried out an observational cohort study to investigate the management of chronic cough in primary care. Methods; We evaluated general practice referral letters and hospital records of 66 consecutive patients attending general respiratory and specialist cough clinics between February 2011 and May 2012. Patients undergoing spirometry, chest X-ray (CXR) and treatment trials of proton pump inhibitors (PPI), oral and inhaled corticosteroids (OCS/ ICS), nasal corticosteroids and antihistamines were recorded. Data was stored in a secure database and analysed using graph pad (California USA). Results; The mean age of patients referred with chronic cough from a primary care centre was 55(15) years, 62% were female and 7.5% were smokers. CXR were performed in 51.5% of patients and 16.6% had spirometry. Trials of PPIs were prescribed in 16.6% of patients. ICS/OCS were prescribed in 34.8% of patients. 6% of patients were prescribed an antihistamine and 12.1% of patients received nasal corticosteroids. Conclusion; These data demonstrate that patients with chronic cough are not receiving the minimum diagnostic standard of CXR and spirometry in primary care (BTS cough guidelines 2006). There is considerable room for improvement for conducting trials of therapy prior to referral to specialist clinics. Secondary care physicians should work together with GPs to address this to achieve earlier diagnosis and treatment of chronic cough.