Phase Locking the Spin Precession in a Storage Ring.

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.

How to Reach a Thousand-Second in-Plane Polarization Lifetime with 0.97-GeV/c Deuterons in a Storage Ring.

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.

New Method for a Continuous Determination of the Spin Tune in Storage Rings and Implications for Precision Experiments.

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.

Changing from a specialized surgical observation unit to an interdisciplinary surgical intensive care unit can reduce costs and increase the quality of treatment.

BACKGROUND AND OBJECTIVES: In Germany there is considerable variability in the organizational forms of intensive-care medicine. We present economical data that arose during the reorganization of an intensive care unit with the implementation of the continuous presence of a trained intensivist. The unit was changed from an intensive-observational unit managed by four surgical departments without continuous presence of a trained intensivist to an interdisciplinary surgical intensive care unit managed by the Department of Anaesthesia in co-operation with the surgical departments with the continuous presence of trained intensivists. METHODS: Measurement of costs for personnel, medical equipment and external services, revenues, length of hospital stay and complications of cardiac surgical patients. RESULTS: Per year costs for personnel increased by approximately euro240,000, while expenses for medical equipment were reduced by euro245,000. In all, 466 hospital days were saved by the reduction in the length of hospital stay, providing capacity for 22 additional cardiac surgical cases. In addition, the presence of trained intensivists made it possible to provide care for more severely ill patients, which gained approximately 100 additional case-mix points and increased the hospital's revenues by more than euro300,000. Emergency readmission to the intensive care unit was reduced by 17%. The number of patients requiring renal replacement therapy and those developing non-occlusive mesenteric ischaemia was substantially reduced. CONCLUSION: In addition to the medical advantages, staffing the intensive care unit with trained intensivists 24 h a day was of appreciable economical benefit.

Nitric oxide synthase inhibition versus norepinephrine in ovine sepsis: effects on regional blood flow.

Hypotension is a serious problem in septic patients. We investigated regional perfusion in several organs during treatment of hyperdynamic sepsis in sheep. Sepsis was induced and maintained for the entire experiment with a continuous infusion of live Pseudomonas aeruginosa. Treatment with either norepinephrine or the nitric oxide synthase inhibitor L omega-mono-methyl-arginine (L-NMMA) was begun after 24 h of sepsis and continued for 24 h. The norepinephrine dosage was adjusted to achieve the same increase in mean arterial pressure as that obtained by a fixed dose of L-NMMA (7 mg/kg/h). Blood flows were analyzed by the microsphere technique. Both compounds restored blood pressure effectively, but only L-NMMA caused a significant increase in systemic vascular resistance, concomitant with a significant fall in cardiac output. Sepsis caused an increase in myocardial blood flow and a redistribution of blood flow away from the pancreas and the stomach. Renal blood flow was not significantly elevated. During treatment with either compound, renal blood flow remained unchanged, despite a fall in cardiac output in the L-NMMA group. Unchanged renal blood flow combined with the restoration of arterial blood pressure caused a significant increase in urine output. Both L-NMMA and norepinephrine caused a redistribution of blood flow to the colon. Pancreatic blood flow was further reduced by L-NMMA but the oxygen extraction improved simultaneously, so that oxygen availability in the pancreas might have been unchanged. Because ischemic pancreatitis in sepsis is likely to trigger multiorgan failure, further investigations in that area are desirable.

S-ethylisothiourea, a nonamino acid inhibitor of nitric oxide synthase, reverses septic vasodilation in sheep.

S-ethylisothiourea (3936W92) is a nonamino acid antagonist of nitric oxide synthase. Its selectivity for the inducible form of nitric oxide synthase is twice as high as for the constitutive form of the enzyme. We tested 3936W92 in 20 sheep, which were surgically prepared for chronic study. In all sheep, a hyperdynamic sepsis was induced by a continuous infusion of live Pseudomonas aeruginosa. After 24 h of sepsis, nine sheep received a continuous infusion of 3936W92 over the next 24 h, whereas the control group (n = 9) received saline instead. Two sheep died within the first 24 h of sepsis. 3936W92 caused a complete reversal of the hyperdynamic circulation, while sheep in the control group remained hyperdynamic. Although the cardiac index decreased significantly during treatment with 3936W92 (7.9 +/- .8 vs. 6.0 +/- .7 l/min/m2), a simultaneous increase in oxygen extraction prevented oxygen consumption from falling.

Inhalation injury increases the anastomotic bronchial blood flow in the pouch model of the left ovine lung.

Pulmonary parenchymal damage often occurs after airway injury. Bronchial venous drainage empties into the pulmonary microvasculature. We developed an in vivo model to study the bronchopulmonary portal system after smoke inhalation injury. Eight ewes were instrumented with hydraulic occluders on the left pulmonary artery (LPA), the left pulmonary vein, and the bronchoesophageal artery (BEA); a catheter in the LPA; and Swan-Ganz and femoral artery catheters. The vasculature between the occluders was defined as pouch. At stable mean arterial and right pulmonary arterial pressures, LPA occlusion reduced the left pulmonary artery pressure (LPAP) from 17 +/- 1 mmHg to 8 +/- 1 mmHg (p < .05). After left pulmonary vein occlusion, LPAP rose to 28 +/- 4 mmHg (p < .05 vs. baseline), indicating that systemic blood had entered the pouch. Opening the pouch to atmospheric pressure revealed an anastomotic bronchial blood flow (anastomotic Qbr) of .76 +/- .11% of cardiac output (CO). BEA occlusion reduced the anastomotic Qbr to .32 +/- .06% of CO (p < .05). Smoke inhalation injury resulted in a further increase in the maximal LPAP to 38 +/- 5 mmHg (p < .05 vs. right pulmonary artery pressure). The anastomotic Qbr rose to 1.29 +/- .13% of CO (p < .05) and was reduced to .40 +/- .09% of CO (p < .05) by BEA occlusion. Inhalation injury increased the anastomotic Qbr mainly due to BEA vasodilatation. Because the BEA supplies the injured airway, it may deliver deleterious material to the lung parenchyma.

Nitric oxide and endothelial permeability.

Nitric oxide synthase inhibition reverses systemic vasodilation during sepsis but may increase endothelial permeability. To assess adverse effects on the pulmonary vasculature, 12 sheep were chronically instrumented with lung lymph fistulas and hydraulic pulmonary venous occluders. Escherichia coli endotoxin (lipopolysaccharide; 10 ng . kg-1 . min-1) was continuously infused for 32 h. After 24 h, six animals received 25 mg/kg of Nomega-nitro-L-arginine methyl ester (L-NAME), and six received saline. All sheep developed a hyperdynamic circulatory response and elevated lymph flows by 24 h of lipopolysaccharide infusion. L-NAME reversed systemic vasodilation, increased pre- and postcapillary pulmonary vascular resistance index, pulmonary arterial pressure, and, transiently, effective pulmonary capillary pressure. Lung lymph flows were not different between groups at 24 h or thereafter. Calculated as changes from baseline, however, lung lymph flow was higher in the L-NAME group than in the control animals, with a trend toward lower lymph-to-plasma protein concentration ratio at 25 h. Permeability analysis at 32 h by the venous occlusion technique showed normal reflection coefficients and elevated filtration coefficients without differences between groups. Reversal by L-NAME of the systemic vasodilation during endotoxemia was associated with high pulmonary vascular resistance without evidence of impaired pulmonary endothelial barrier function.

Increased organ blood flow in chronic endotoxemia is reversed by nitric oxide synthase inhibition.

We evaluated regional blood flows in a hyperdynamic sepsis model and the reversal of increased flows by blockade of nitric oxide (NO) synthase. Seven awake sheep were continuously infused with Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1] for 48 h. The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg) was injected after 24 h. Blood flows to systemic organs were determined with the radioactive microsphere technique. LPS induced elevation of cardiac index by 36% (P < 0.05) and a fall in systemic vascular resistance index by 37% (P < 0.05) at 0 h [time of L-NAME administration, 24 h after infusion of LPS had begun] L-NAME administration normalized cardiac index [6.1 +/- 0.5 at 4 h posttreatment, 6.1 +/- 0.5 l.min-1.m-2 at -24 h (baseline)] and systemic vascular resistance index (1,333 +/- 105 at 4 h posttreatment, 1,280 +/- 163 dyn.s.cm-5.m2 at -24 h) and reduced all regional blood flows to near-baseline levels for the remainder of the study period (24 h). O2 consumption was unaffected by treatment.

Inhaled nitric oxide selectively reduces pulmonary hypertension after ovine smoke inhalation but does not improve oxygenation.

Inhaled nitric oxide (NO) is known to selectively reduce pulmonary hypertension and improve the ventilation-perfusion relationship in subjects with lung injury of various origin. However, some forms of lung injury do not react to inhaled NO at all, or show only a reduction in pulmonary arterial pressure. Very little is known about the effects of inhaled NO after smoke inhalation injury. We investigated the effects of inhaled NO in an established model of ovine smoke inhalation injury. Chronically instrumented sheep (n = 8) had tracheostomies and were insufflated with smoke generated from burning cotton cloth (4 times at 12 breaths each). They were then connected to a ventilator with oxygen-enriched air to achieve arterial oxygen tensions within the normal range. After 48 hours, NO was added to the inspired gas in ascending concentrations of up to 100 ppm. Systemic and pulmonary hemodynamics as well as oxygen transport were analyzed. Inhaled NO dose dependently lowered the pulmonary hypertension. Concentrations higher than 20 ppm did not further reduce the pulmonary artery pressure. Right ventricular stroke work index was significantly improved owing to the reduction in pulmonary vascular resistance. Arterial oxygenation, however, was not optimized by inhaled NO, probably because of interstitial edema formation.

Non-return valves do not prevent backflow and bacterial contamination of intravenous infusions.

Non-return valves (NRVs) are designed to avoid backflow of infusion fluid against the designated direction of flow (DDF) when more than one infusion is delivered via one venous access. We tested in vitro whether NRVs reliably prevent flow against the DDF at clinically relevant low flow rates. Since catheter-related infections caused by the infusion of contaminated fluids represent a relevant problem in patient care, we tested whether NRVs preclude bacterial contamination of infusions proximal to the NRVs and thus might play a role in preventing healthcare-associated infections. Additionally, the incidence of bacterial contamination of drips and infusion fluids in our intensive care unit (ICU) was quantified. In vitro, a low flow against the DDF of ten examples each of five different NRV models was applied and the integrity for fluid and transmigration of three different indicator micro-organisms was tested. Second, we investigated whether contamination of intravenous infusion tubing collected from patients treated on our ICU occurred. Largely independent from the model, 40% of the tested NRVs were not leak-tight for fluids when a pressure against the DDF was built up slowly. In 30%, bacteria migrated against the DDF and were detected proximal to the valve. In 6.7% of the tubing samples collected from ICU patients we detected bacterial contamination. In conclusion, contamination of drips is a relevant problem on ICU. NRVs neither reliably prevent backflow of fluids nor serve as micro-organism filters. Therefore they cannot be recommended as a way of reducing healthcare-associated infections.

[Evidence-based infection control methods using spa genotyping for MRSA spread in hospitals]. / Evidenzbasierte Hygienemassnahmen mittels spa-Typisierung bei MRSA-Häufungen im Krankenhaus.

BACKGROUND AND OBJECTIVE: Isolation of methicillin resistant Staphylococcus aureus (MRSA) often implies rigorous infection control measures. The use of rapid and accurate typing is required to monitor their spread. Prompt identification of epidemic MRSA is crucial to control an outbreak, in order to avoid unnecessary interventions in patients and staff. In this study we evaluated protein A ( spa) gene repeat sequence analysis for MRSA typing in a hospital. METHODS: In 2003, all non-replicate MRSA-strains from staff and patients admitted to the University Hospital Münster (1480 beds), Germany, were spa typed. The spa types were assigned using the Ridom StaphType software. Typing results were correlated with the epidemiological findings of each MRSA isolate. RESULTS: Assignment of spa types was possible for all 175 MRSA isolates and provided rapid (mean, 2 days) typing results. spa typing method yielded 34 spa types. Synchronizing the sequencing results with a central database (http://www.spaServer.ridom.de) created a reproducible and uniform nomenclature for easy intra- and inter-hospital comparisons. CONCLUSION: spa typing makes continuous and fast MRSA typing possible for hospital isolates. The differentiation between outbreaks and accidental accumulations due to imported MRSA was easily possible and allowed implementation of focused and evidence-based infection control measures.

[Limitations of inhaled vasodilators]. / Grenzen inhalativer Vasodilatatoren.

Treatment of pulmonary hypertension is an important issue in intensive care. One therapeutic regimen involves the intravenous administration of prostacyclin (PGI2). This, however, is accompanied by diminished hypoxic pulmonary vasoconstriction, reduced arterial oxygenation, and systemic vasodilation. Thus, its clinical usefulness is limited. However, the inhalation of vasodilators such as nitric oxide (NO) or nebulized PGI2 causes a selective pulmonary vasodilation in ventilated alveoli and improved gas exchange, without any systemic vasodilation. It has therefore gained importance for the treatment of pulmonary failure associated with high shunt fractions. However, the inhalation of vasodilators may have adverse effects: in the case of NO, toxic side effects are predominant (MetHb, NOx), whereas in the case of PGI2, technical problems in terms of dosing and administration safety are of major interest. Furthermore, some patients do not respond to the treatment. In some individuals a reduction in pulmonary hypertension can be seen, while others lack even pulmonary vasodilation. The exact pathophysiological mechanisms remain to be investigated.

Fat elimination from autologous blood.

Bowl-based autotransfusion devices reduce the amount of fat found in shed blood, but cannot completely eliminate fat particles. When fat is seen on the surface of the processed blood, this blood should be filtered with a leukocyte removal filter before retransfusion.

Nitric oxide synthase inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep.

OBJECTIVES: To investigate the effects of Nomega-mono-methyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, on hemodynamics, oxygen transport, and regional blood flow in an ovine model of hyperdynamic sepsis and to compare these effects with the responses to norepinephrine. DESIGN: Prospective, nonrandomized, controlled experimental study with repeated measures. SETTING: Investigational intensive care unit at a university medical center. SUBJECTS: Twenty-five female, healthy, adult sheep of the Merino breed, divided into three groups: nine control sheep; eight sheep treated with L-NMMA; and eight sheep treated with norepinephrine. INTERVENTIONS: All sheep were chronically instrumented. After a 5-day recovery period, a continuous infusion of live Pseudomonas aeruginosa (2.5 x 10(6) colony-forming units/min) was started and maintained for the remainder of the experiment. After 24 hrs of sepsis, eight sheep received L-NMMA (7 mg/kg/hr), eight sheep received norepinephrine, and nine sheep received the vehicle alone (0.9% saline). The norepinephrine dosage was continuously and individually adjusted to achieve the same increase in blood pressure as was observed in a matched sheep of the L-NMMA group. MEASUREMENTS AND MAIN RESULTS: After 24 hrs of sepsis, all sheep developed a hyperdynamic circulatory state with increased cardiac indices and reduced arterial pressures, and systemic vascular resistances. L-NMMA reversed the hyperdynamic circulation, causing an increase in arterial pressure by peripheral vasoconstriction. Norepinephrine led to an increase in blood pressure by augmenting cardiac indices, leaving the systemic vascular resistance unaffected. The norepinephrine dose needed to keep the blood pressure high had to be continuously increased, reflecting the reduced vascular responsiveness to catecholamines during sepsis. Renal blood flow remained unaffected by all treatment forms. Norepinephrine and L-NMMA led to a dramatic increase in urine production. Blocking the nitric oxide synthase with L-NMMA did not interfere with the host's pulmonary ability to clear bacteria, nor did treatment with norepinephrine. CONCLUSIONS: Blocking nitric oxide synthase had a marked vasoconstrictive effect. Both norepinephrine and L-NMMA increased arterial pressure without reducing renal blood flow, leading to an improved renal function.

[Prolonged muscle weakness in intensive care patients with special attention to the so-called intensive care polyneuromyopathy]. / Prolongierte Muskelschwäche des Intensivpatienten unter besonderer Berücksichtigung der sog. Intensive-Polyneuromyopathie.

Generalized muscle weakness in critically ill patients can result in prolonged periods of artificial ventilation and longer stays in the intensive care unit. Both neuropathic (critical illness polyneuropathy) and myopathic (critical illness myopathy) abnormalities seem to play an important role for this prolonged weakness. This article reviews its complex differential diagnosis with special emphasis on the current understanding of the neuromuscular syndromes. An efficient diagnostic plan is necessary for the exclusion of other curable causes of prolonged muscle weakness even in the presence of polyneuromyopathic changes. Psychological support of the patient and prophylaxis of secondary complications of prolonged immobilization are crucial when specific therapy is not possible.

The atrial natriuretic peptide receptor antagonist HS 142-1 improves cardiovascular filling and mean arterial pressure in a hyperdynamic ovine model of sepsis.

OBJECTIVE: To test whether systemic vascular resistance and mean arterial pressure increase during the administration of the atrial natriuretic peptide antagonist, HS 142-1, in ovine experimental hyperdynamic sepsis. DESIGN: Prospective trial. SETTING: Research laboratory at a large university medical center. SUBJECTS: Chronically instrumented Merino breed ewes (n = 14). INTERVENTIONS: Continuous infusion of Pseudomonas aeruginosa (2.5 x 10(6) colony-forming units/min) for the experimental period of 48 hrs. One group (HS 142-1) received a continuous infusion of HS 142-1 (3 mg/kg/hr) from 40 to 48 hrs; the remaining sheep ("control") were given the vehicle sodium chloride 0.9%. MEASUREMENTS AND MAIN RESULTS: All sheep developed a hyperdynamic cardiovascular response by 40 hrs that was characterized by low values of systemic vascular resistance index (p < .05) and mean arterial pressure (p < .05), and an increased cardiac index (p < .05). HS 142-1 increased cardiac filling pressures (p < .05) without apparent effects on fluid balance, and was associated with a significantly (p < .05) higher mean arterial pressure than was found in the control group at 44 and 48 hrs. HS 142-1 did not change systemic vascular resistance index. At 44 and 48 hrs, cardiac index values were found to have significantly (p < .05) increased in the animals receiving HS 142-1, when these data were compared with cardiac output values at 40 hrs. CONCLUSION: HS 142-1 increases cardiac filling pressures and maintains mean arterial pressure in hyperdynamic sepsis without reversal of sepsis-induced vasodilation.

Noradrenaline and nomega-monomethyl-L-arginine (L-NMMA): effects on haemodynamics and regional blood flow in healthy and septic sheep.

This prospective, non-randomized, controlled experimental study looks at the effects of N(omega)-monomethyl-L-arginine (L-NMMA) on haemodynamics, oxygen transport and regional blood flow in healthy and septic sheep, and compares these effects with those of noradrenaline (NA; norepinephrine). All sheep were chronically instrumented. Six sheep received L-NMMA (7 mg.kg(-1).h(-1)), six sheep received NA, and seven sheep received the carrier alone (0.9% NaCl). The NA dosage was continuously and individually adjusted to achieve the same increase in blood pressure as observed in matched sheep of the L-NMMA group (non-septic phase). Treatment was discontinued after 3 h. Sepsis was initiated and maintained by a continuous infusion of live Pseudomonas aeruginosa. After 24 h of sepsis, the sheep were again challenged over a treatment period of 3 h with their previously assigned drug (septic phase). During the non-septic phase of the experiment, NA and L-NMMA both caused an increase in mean arterial pressure (MAP) through vasoconstriction. Ater 24 h of sepsis, all sheep developed a hyperdynamic circulatory state. While L-NMMA caused an increase in MAP through intense vasoconstriction, NA caused MAP to increase through a further elevation of the cardiac index. The NA dosage needed was significantly higher in the septic phase compared with the non-septic phase, reflecting a reduced vascular responsiveness to catecholamines during sepsis. Renal blood flow remained unchanged during either treatment in both the non-septic and the septic phases. Nevertheless, urine output increased during NA treatment in both the non-septic and the septic phases, while L-NMMA caused urine output to increase only under septic conditions.