ABSTRACT
The cross section of the process e^{+}e^{-}âπ^{+}π^{-} has been measured in the center-of-mass energy range from 0.32 to 1.2 GeV with the CMD-3 detector at the electron-positron collider VEPP-2000. The measurement is based on an integrated luminosity of about 88 pb^{-1}, of which 62 pb^{-1} represent a complete dataset collected by CMD-3 at center-of-mass energies below 1 GeV. In the dominant region near the ρ resonance a systematic uncertainty of 0.7% was achieved. The implications of the presented results for the evaluation of the hadronic contribution to the anomalous magnetic moment of the muon are discussed.
ABSTRACT
This Letter reports the successful use of feedback from a spin polarization measurement to the revolution frequency of a 0.97 GeV/c bunched and polarized deuteron beam in the Cooler Synchrotron (COSY) storage ring in order to control both the precession rate (≈121 kHz) and the phase of the horizontal polarization component. Real time synchronization with a radio frequency (rf) solenoid made possible the rotation of the polarization out of the horizontal plane, yielding a demonstration of the feedback method to manipulate the polarization. In particular, the rotation rate shows a sinusoidal function of the horizontal polarization phase (relative to the rf solenoid), which was controlled to within a 1 standard deviation range of σ=0.21 rad. The minimum possible adjustment was 3.7 mHz out of a revolution frequency of 753 kHz, which changes the precession rate by 26 mrad/s. Such a capability meets a requirement for the use of storage rings to look for an intrinsic electric dipole moment of charged particles.
ABSTRACT
A new experiment is described to detect a permanent electric dipole moment of the proton with a sensitivity of 10-29 e â cm by using polarized "magic" momentum 0.7 GeV/c protons in an all-electric storage ring. Systematic errors relevant to the experiment are discussed and techniques to address them are presented. The measurement is sensitive to new physics beyond the standard model at the scale of 3000 TeV.
ABSTRACT
We observe a deuteron beam polarization lifetime near 1000 s in the horizontal plane of a magnetic storage ring (COSY). This long spin coherence time is maintained through a combination of beam bunching, electron cooling, sextupole field corrections, and the suppression of collective effects through beam current limits. This record lifetime is required for a storage ring search for an intrinsic electric dipole moment on the deuteron at a statistical sensitivity level approaching 10^{-29} e cm.
ABSTRACT
A new method to determine the spin tune is described and tested. In an ideal planar magnetic ring, the spin tune-defined as the number of spin precessions per turn-is given by ν(s)=γG (γ is the Lorentz factor, G the gyromagnetic anomaly). At 970 MeV/c, the deuteron spins coherently precess at a frequency of ≈120 kHz in the Cooler Synchrotron COSY. The spin tune is deduced from the up-down asymmetry of deuteron-carbon scattering. In a time interval of 2.6 s, the spin tune was determined with a precision of the order 10^{-8}, and to 1×10^{-10} for a continuous 100 s accelerator cycle. This renders the presented method a new precision tool for accelerator physics; controlling the spin motion of particles to high precision is mandatory, in particular, for the measurement of electric dipole moments of charged particles in a storage ring.
ABSTRACT
Following cardiac arrest a 41-year-old patient was resuscitated for 40 min and required mechanical ventilation for 27.5 h. Acute shortness of breath and inspiratory stridor developed 7 days after successful extubation. Bronchoscopy revealed a subtotal tracheal stenosis caused by extensive fibrinous membranes. Local ischaemia caused by cuff pressure seems to be a likely explanation with an additional component of general hypoperfusion and haemodynamic instability which led to gastric bleeding (classification according to Forrest IIc) from ischaemic ulcers.
Subject(s)
Cardiopulmonary Resuscitation , Respiration, Artificial/adverse effects , Tracheal Stenosis/etiology , Acute Disease , Adult , Blood Pressure/physiology , Bronchoscopy , Electrocardiography , Fibrosis/pathology , Gastrointestinal Hemorrhage/etiology , Glottis/pathology , Humans , Male , Respiratory Sounds/etiology , Tracheal Stenosis/complications , Tracheal Stenosis/pathologyABSTRACT
BACKGROUND: Balsalazide is a new 5-aminosalicylic acid (5-ASA) containing prodrug. Its efficacy in comparison with standard mesalazine therapy and the optimum dose for maintaining remission of ulcerative colitis are still unclear. AIMS: To compare the relapse preventing effect and safety profile of two doses of balsalazide and a standard dose of Eudragit coated mesalazine. METHODS: A total of 133 patients with ulcerative colitis in remission were recruited to participate in a double blind, multicentre, randomised trial: 49 patients received balsalazide 1.5 g twice daily, 40 received balsalazide 3.0 g twice daily, and 44 received mesalazine 0.5 g three times daily. Efficacy assessments were clinical activity index (CAI) and endoscopic score according to Rachmilewitz, and a histological score. In addition, laboratory tests were performed and urinary excretion of 5-ASA and its metabolite N-Ac-5-ASA was analysed. The study lasted for 26 weeks. RESULTS: Balsalazide 3.0 g twice daily resulted in a significantly higher clinical remission rate (77.5%) than balsalazide 1.5 g twice daily (43.8%) and mesalazine 0.5 g three times daily (56.8%) (p=0.006). The respective times to relapse were 161 days, 131 days (p=0.003), and 144 days (NS). Accordingly, pairwise contrasts of the final endoscopic score demonstrated a significant difference (p=0.005) between the two balsalazide treatment groups while differences between either of these two groups and mesalazine were not statistically significant. Patients treated with balsalazide excreted less 5-ASA and N-Ac-5-ASA than patients receiving mesalazine but these differences were not statistically significant. Discontinuation of the trial because of adverse effects occurred in nine patients: three in the balsalazide 1.5 g twice daily group, two in the balsalazide 3.0 g twice daily group, and four in the mesalazine 0.5 g three times daily group. No clinically important new drug safety related findings were identified in this study. CONCLUSIONS: High dose balsalazide (3.0 g twice daily) was superior in maintaining remission in patients with ulcerative colitis compared with a low dose (1.5 g twice daily) or a standard dose of mesalazine (0.5 g three times daily). All three treatments were safe and well tolerated.
Subject(s)
Aminosalicylic Acids/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Colitis, Ulcerative/drug therapy , Mesalamine/administration & dosage , Prodrugs/administration & dosage , Aminosalicylic Acids/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Colitis, Ulcerative/pathology , Colitis, Ulcerative/urine , Colon/pathology , Double-Blind Method , Drug Administration Schedule , Female , Humans , Male , Mesalamine/adverse effects , Mesalamine/urine , Phenylhydrazines , Prodrugs/adverse effectsABSTRACT
We report on first measurements with polarized electrons stored in a medium-energy ring and with a polarized internal target. Polarized electrons were injected at 442 MeV (653 MeV), and a partial (full) Siberian snake was employed to preserve the polarization. Longitudinal polarization at the interaction point and polarization lifetime of the stored electrons were determined with laser backscattering. Spin observables were measured for electrodisintegration of polarized 3He, with simultaneous detection of scattered electrons, protons, neutrons, deuterons, and 3He nuclei, over a large phase space.
ABSTRACT
OBJECTIVE: Endomysial autoantibodies (EmA) are specific for celiac disease. The target antigen has been identified as tissue tranglutaminase (tTG). Our aim was to study the accuracy of a newly developed enzyme-linked immunosorbent assay (ELISA) for easy detection of tTG autoantibodies. METHODS: Thirty-one sera from patients with histologically proven celiac disease and 23 healthy controls were examined for EmA using monkey esophagus and human umbilical cord as substrate. IgA-tTG autoantibodies were determined by newly developed ELISA. Additionally, sera from patients with dermatitis herpetiformis (n = 20), inflammatory bowel disease (IBD; n = 32), chronic liver disease (n = 36), and diabetes mellitus (n = 19) were tested. RESULTS: The sensitivity of the tTG autoantibody ELISA accounted for 90% detection in patients with untreated celiac disease. The specificity was 76% owing to positive values in the lower range in patients with IBD (15%), chronic liver disease (36%), and diabetes (22%), all of whom were negative for EmA. In dermatitis herpetiformis patients 90% were EmA-positive. Of these, only 47% showed elevated tTG autoantibodies. Preincubation of sera from dermatitis patients with tTG abolished immunofluorescent staining of endomysial structures. CONCLUSION: Detection of mid- to high-titer tTG autoantibodies is highly specific for celiac disease. However, in the low-titer range, overlap exists with liver disease, IBD, and diabetes. Tissue transglutaminase autoantibodies may evolve as a new screening and follow-up method for celiac disease. Although tTG seems to be a major autoantigen in dermatitis herpetiformis, the low sensitivity of both tTG ELISA and immunofluorescence using human umbilical cord suggests differential involvement of tTG in this disease.
Subject(s)
Autoantibodies/analysis , Celiac Disease/immunology , Dermatitis Herpetiformis/immunology , Transglutaminases/immunology , Animals , Enzyme-Linked Immunosorbent Assay , Esophagus/immunology , Fluorescent Antibody Technique , Haplorhini/immunology , Humans , In Vitro Techniques , Sensitivity and Specificity , Umbilical Cord/immunologyABSTRACT
BACKGROUND: Concentrations of proinflammatory cytokines are increased in the intestinal mucosa of patients with active Crohn's disease. Experimental immunotherapeutic interventions with anticytokine agents in refractory Crohn's disease show that tumour necrosis factor alpha (TNF alpha) may be an important mediator of inflammation. We investigated the relation between production of TNF alpha and interleukin 1beta by mononuclear cells of the colonic lamina propria in patients with remitting Crohn's disease and the risk of relapse. METHODS: We followed up 137 patients with Crohn's disease in steroid-induced remission for 1 year. Secretion of proinflammatory cytokines (tumour necrosis factor alpha [TNF alpha] and interleukin 1beta) was assessed after short-term culture of human lamina propria mononuclear cells. FINDINGS: Increased secretion of TNF alpha and interleukin 1beta were predictive for acute relapses within the next year. Site and extent of disease, baseline demographics, and serum acute-phase proteins had little predictive value. INTERPRETATION: TNF alpha is important as a target molecule for immune interventions in Crohn's disease. The capacity to produce TNF alpha or interleukin 1beta may identify patients who would benefit from anti-inflammatory remission maintenance.
Subject(s)
Crohn Disease/metabolism , Inflammation Mediators/metabolism , Interleukin-1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Biomarkers/analysis , Cells, Cultured , Colon/metabolism , Crohn Disease/diagnosis , Crohn Disease/drug therapy , Humans , Recurrence , Risk FactorsSubject(s)
Antibodies, Monoclonal/therapeutic use , Crohn Disease/therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Antibodies, Monoclonal/immunology , Crohn Disease/immunology , Disease Progression , Drug Administration Schedule , Humans , Infusions, Intravenous , Mice , Treatment Outcome , Tumor Necrosis Factor-alpha/immunologyABSTRACT
BACKGROUND & AIMS: There is conflicting evidence concerning whether muscarinic regulation of gastrin release in humans is a direct or indirect effect on antral G cells. The present experiments were designed to resolve this question using an isolated human G-cell preparation. METHODS: The ability of muscarinic agonists to stimulate or inhibit gastrin release was assessed with or without an immunoneutralizing somatostatin antibody or an m3 receptor antagonist. The effect of secretogogues on G and D cells was monitored by intracellular calcium imaging. RESULTS: Muscarinic agonists failed to stimulate gastrin release, even after the removal of somatostatin-induced inhibition. Our group has previously shown that muscarinic agonists stimulated somatostatin release from antral D cells. Methacholine (100 mumol/L) increased intracellular calcium levels in cocultured D cells; this increase was inhibited by the m3 receptor antagonist 4-diphenylacetoxy-n-methylpiperidine methiodide. Gastrin cells in the same field of view lacked a response to methacholine but showed a clear response to 10 nmol/L bombesin. CONCLUSIONS: The experiments indicate that vagal control of gastrin release in humans is indirect; stimulation would be achieved by the activation of intrinsic gastrin-releasing peptide neurons, and inhibition would be via the paracrine action of somatostatin released from adjacent D cells.
Subject(s)
Gastrins/metabolism , Muscarinic Agonists/pharmacology , Pyloric Antrum/drug effects , Pyloric Antrum/metabolism , Adult , Antibodies/immunology , Bombesin/pharmacology , Calcium/metabolism , Carbachol/pharmacology , Cells, Cultured , Female , Humans , Male , Methacholine Chloride/pharmacology , Middle Aged , Muscarinic Antagonists/pharmacology , Piperidines/pharmacology , Pyloric Antrum/cytology , Somatostatin/immunologyABSTRACT
Adrenomedullin (AM) is a novel vasorelaxing peptide which was originally isolated from the extracts of human pheochromocytoma. It is produced by a number of organs among which the adrenal gland exhibits by far the highest concentrations. The peptide circulates in blood and its plasma levels have been reported to be increased in several diseases such as renal failure and sepsis. In the present study plasma concentrations of AM were measured in various forms of severe illness and compared to clinical and biochemical parameters in order to gain an insight into the factors controlling the plasma levels of this peptide. The highest concentrations of AM were found in patients with sepsis (344.4 +/- 60.4 pg/ml, n = 16) who exhibited up to 12-fold higher levels than a group of healthy subjects (74.1 +/- 4.1 pg/ml, n = 20). Markedly elevated levels were also measured in hemorrhagic (250.1 +/- 37.9 pg/ml, n = 9) and cardiogenic (216.2 +/- 29.4 pg/ml, n = 7) shock as well as in patients with cancer of the gastrointestinal tract (155.6 +/- 32.5 pg/ml, n = 11) or the lungs (146.5 +/- 19.1 pg/ml, n = 22). Plasma AM levels were positively correlated with serum creatinine concentrations in shock (r = 0.06, p < 0.001) and with C-reactive protein levels in patients with cancer (r = 0.64, p < 0.001) or sepsis (r = 0.63, p < 0.01). In order to examine the potential role of the adrenal gland as a site of AM release, hypoglycemia was induced in a group of healthy volunteers by graded infusion of insulin. Despite a more than 20-fold increase in plasma adrenalin indicating maximal stimulation of the adrenal medulla, no significant alterations of the plasma AM levels were observed. The study demonstrates that not only sepsis but also various forms of cancer and shock are associated with high levels of circulating AM. The correlation with C-reactive protein levels suggests a role of cytokines in mediating the elevations in plasma AM observed in sepsis and cancer. Reduced clearance of the peptide by the kidneys may be one of the mechanisms involved in the accumulation of AM in shock. The adrenal gland appears not to be a major source for circulating AM.
Subject(s)
Adrenal Medulla/physiology , C-Reactive Protein/metabolism , Peptides/blood , Vasodilator Agents/blood , Adrenomedullin , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Gastrointestinal Hemorrhage/blood , Humans , Kidney Failure, Chronic/blood , Male , Middle Aged , Neoplasms/blood , Shock, Cardiogenic/blood , Systemic Inflammatory Response Syndrome/bloodABSTRACT
The specific cholecystokinin (CCK) receptor antagonist loxiglumide has been used in several human and animal studies to investigate the role of CCK in gastrointestinal physiology. In the present study, the interference of this CCK receptor antagonist with hepatic transport processes was characterized in the perfused rat liver. Indocyanine green, an organic dye which is secreted into bile without being metabolized, was taken up in control experiments at a rate of 68.1 +/- 7.7%. The CCK receptor antagonist lowered the extraction to 0.5 +/- 2.6% (P < 0.001). The compound diminished the hepatic extraction of CCK-8 from 90.95 +/- 2.60% to 4.90 +/- 1.95% (P < 0.001) and of gastrin from 22.2 +/- 1.1% to 8.2 +/- 1.9% (P < 0.001). The hepatic extraction of lidocaine, which is metabolized by the cytochrome P450 system, was only slightly altered. For leukotrienes and taurocholate, the rate-limiting step for transport into bile is secretion across the canalicular membrane; the hepatic extraction of leukotriene D4 was markedly diminished by loxiglumide whereas the transport of taurocholate was only slightly inhibited. The present study demonstrates that the specific CCK receptor antagonist loxiglumide diminished the hepatic extraction of various substances, including peptides and organic anions. It did not interfere with the cytochrome P450 system. The pronounced reduction of hepatic uptake of indocyanine green and leukotriene may be due to an interference with the transport system of these substances in the liver.
Subject(s)
Hormone Antagonists/pharmacology , Liver/metabolism , Proglumide/analogs & derivatives , Receptors, Cholecystokinin/metabolism , Animals , Bile/chemistry , Biological Transport/drug effects , Cholagogues and Choleretics/pharmacology , Gastrins/analysis , Gastrins/metabolism , Indocyanine Green/pharmacokinetics , Leukotriene D4/pharmacology , Liver/blood supply , Liver/drug effects , Male , Portal Vein , Proglumide/pharmacology , Rats , Rats, Wistar , Receptors, Cholecystokinin/agonists , Receptors, Cholecystokinin/antagonists & inhibitors , Sincalide/analysis , Sincalide/metabolism , Taurocholic Acid/pharmacologyABSTRACT
BACKGROUND: The physiological relevance of duodenal bile acids in the control of cholecystokinin release and pancreatic enzyme secretion is still unknown. AIMS: To provide a near physiological situation by perfusing a bile acid mixture mimicking the individual endogenous bile acid composition of the person under investigation. For maximal reduction of endogenous bile output the CCK-A receptor antagonist loxiglumide was infused intravenously. SUBJECTS AND METHODS: Seven healthy volunteers were studied on four different days by a duodenal marker perfusion technique. The individual bile acid composition in duodenal juice and test meal stimulated bile acid output was assessed on day 1. Bile acids were perfused at an amount of 30 or 100% as determined on day 1 in combination with the test meal in the presence or absence of loxiglumide. Pancreatic enzymes, bilirubin, and bile acid output were determined in duodenal juice. Plasma cholecystokinin (CCK) and plasma pancreatic polypeptide (PP) were measured radioimmunologically. RESULTS: Bile acid perfusion did not significantly alter stimulated pancreatic enzyme, bilirubin or bile acid output or plasma CCK. Loxiglumide did not alter basal CCK release but increased test meal stimulated CCK output fourfold (p < 0.05). The addition of bile acids to the test meal at a dose resembling 30% of bile acid output as determined on day 1 prevented this increase. Plasma PP concentration remained unchanged by bile acids and were mostly undetectable during loxiglumide infusion. CONCLUSIONS: The CCK producing cell is under constant suppression by intraduodenal bile acids which cannot be further enhanced by a physiological bile acid mixture. However, removal of duodenal bile acids by inhibition of gall bladder contraction unmasks this suppression leading to a dramatic increase in plasma CCK levels. As little as one third of postprandially released bile acids completely reverse this effect. Bile acids are the most important luminal regulator of CCK release in humans.
Subject(s)
Bile Acids and Salts/physiology , Cholecystokinin/metabolism , Pancreas/metabolism , Adult , Bile Acids and Salts/pharmacology , Bilirubin/analysis , Bilirubin/metabolism , Duodenum , Hormone Antagonists/pharmacology , Humans , Intestinal Secretions/chemistry , Intestinal Secretions/enzymology , Male , Pancreas/drug effects , Pancreas/enzymology , Pancreatic Polypeptide/blood , Perfusion , Proglumide/analogs & derivatives , Proglumide/pharmacology , Receptors, Cholecystokinin/antagonists & inhibitorsABSTRACT
BACKGROUND: There is no established therapy for maintaining remission in patients with Crohn's disease. Following different suggestions from the literature, two potential interventions for maintaining remission were tested against placebo, using either 5 g/day of a highly concentrated omega-3 fatty acid compound or a carbohydrate-reduced diet (84 g/day). METHODS: A total of 204 patients were recruited after they had had an acute relapse. After remission (CDAI < or = 150) was attained with steroid therapy, patients were randomized to receive either omega-3 fatty acids (n = 70), placebo (n = 65), or diet (n = 69). Low-dose prednisolone was given to all patients for the first 8 weeks of intervention. CDAI and an acute-phase protein (CRP) were used as criteria for a relapse. RESULTS: The proportion of patients without relapse within a year were similar in the placebo and active treatment group (intention-to-treat analysis: placebo, 30%; active treatment, 30%; protocol-adhering patients, 29% versus 28%). Patients did gain benefit (53%; p = 0.023) for as long as they maintained the diet. However, intention-to-treat analysis (diet group, 40%) did not show a noticeable difference when compared with placebo. CONCLUSIONS: Omega-3 fatty acids did not show an effect on extending the remission in Crohn's disease. For the diet patients the question remains whether the noncompliant patients dropped out early because they sensed a relapse approaching or whether their condition deteriorated because they failed to comply with the diet.
Subject(s)
Crohn Disease/diet therapy , Dietary Carbohydrates , Fatty Acids, Omega-3 , Adult , Aged , Anti-Inflammatory Agents/therapeutic use , Combined Modality Therapy , Crohn Disease/drug therapy , Dietary Carbohydrates/administration & dosage , Double-Blind Method , Fatty Acids, Omega-3/administration & dosage , Female , Humans , Male , Middle Aged , Patient Compliance , Prednisolone/therapeutic use , Remission Induction , Statistics as TopicABSTRACT
The rapidly absorbed analog of human insulin, insulin lispro (LP), is characterized by a faster onset of action, a higher peak insulin level, and a shorter duration of action compared with regular insulin (RI). The aim of this study was to investigate whether intensified treatment with either LP or RI influences insulin receptor status. Twelve patients with insulin-dependent diabetes mellitus (IDDM) participating in a multicenter randomized cross-over trial were allocated to this study. Four patients began with LP, whereas eight patients started with RI. Each patient was switched to the other insulin after a 3-month treatment period. Competitive [125I]A-14-insulin binding studies were performed with isolated monocytes. Treatment with insulin lispro increased the total number of insulin binding sites from 9,400 +/- 2,200 (RI) to 20,300 +/- 3,000 (LP)/monocyte (P < 0.001). The insulin concentration required for a 50% competition of [125I]insulin binding (IC50) decreased from 0.6 +/- 0.2 (RI) to 0.1 +/- 0.03 (LP) nmol/L, indicating significantly higher affinity of insulin binding sites during LP treatment (P < 0.001). In additional experiments, the time course of insulin binding was determined after an oral meal. In LP-treated IDDM patients, the affinity and capacity of insulin binding showed a nadir 1 h after insulin injection and a regained binding affinity and capacity 5 h later. These changes observed after LP treatment were comparable to the effect of endogenous insulin secretion in healthy control subjects. In contrast, the IDDM patients who injected RI showed a decreasing insulin binding affinity and capacity, most markedly expressed after 5 h. The corresponding serum levels of insulin were inversely correlated with the affinity and capacity of insulin-binding sites. Pretreatment of cultured human IM-9 lymphoblasts with LP or RI yielded no difference in the down-regulation of insulin binding. In summary, intensified conventional insulin therapy with LP increased the number and affinity of insulin receptors on circulating monocytes to a level similar to that observed in healthy subjects. We conclude that the improved insulin receptor status observed during LP treatment is caused by its more physiological pharmacokinetic profile.