Spectroscopy of nS, nP, and nD Rydberg series of Cs atoms on helium nanodroplets.

The preparation of an artificial superatom consisting of a positive charge inside a superfluid helium nanodroplet and an electron in an orbital surrounding the droplet is of fundamental interest and represents an experimental challenge. In this work, nanodroplets of several thousand helium atoms are doped with single caesium (Cs) atoms. While on the droplet, the Cs valence electron is excited in two steps through an intermediate state into nS, nP, and nD states. The excitation is monitored by laser induced fluorescence or, for high principal quantum numbers, by resonant three-photon-ionization. On-droplet Rydberg excitations are resolved up to about n = 20. The energies are compared with those of free Cs atom Rydberg states and quantum defects as well as the on-droplet ionization threshold are derived.

Establishment of replacement batches for prekallikrein activator in albumin biological reference preparation.

A collaborative study was run by the European Directorate for the Quality of Medicines and HealthCare (EDQM) under the aegis of the Biological Standardisation Programme (BSP) to establish replacement batches of the current Prekallikrein activator in albumin Biological Reference Preparation (BRP) batch 1, the stocks of which were dwindling. Candidate BRP replacement batch 2 and batch 3 were assayed against the 2nd World Health Organization International Standard for Prekallikrein activator, human (2nd IS) and the Prekallikrein activator in albumin BRP batch 1. The candidate batches were manufactured from the same starting material as the current Biological Reference Preparation and the 2nd IS. They consisted of a 20 % solution of albumin lyophilised under the same conditions as the Prekallikrein activator in albumin BRP batch 1. Sixteen laboratories participated in the collaborative study and were requested to assay the candidates by their routine method, complying with the European Pharmacopoeia (Ph. Eur.) general method 2.6.15 for the determination of prekallikrein activator content. A central statistical analysis was performed at the EDQM using in-house calculations of prekallikrein activator contents provided by the participating laboratories. On the basis of the results of this study, which confirmed the assigned potency of 29 IU/vial of Prekallikrein activator in albumin BRP batch 1, the 2 candidate materials were assigned a potency of 30 IU/vial. The 2 candidates were adopted by the Ph. Eur. Commission in March 2008 as Ph. Eur. Prekallikrein activator in albumin Biological Reference Preparation batch 2 and batch 3.

Collaborative study to establish a new biological reference preparation for prekallikrein activator.

An International Collaborative Study was organized to replace the current World Health Organization (WHO) International Standard (IS) for Prekallikrein Activator (PKA) and to establish a European Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP). The project was jointly organized by the European Directorate for the Quality of Medicines (EDQM) and the National Institute for Biological Standards and Control (NIBSC) to identify and calibrate suitable materials that could act as an IS and a Ph. Eur. BRP. The current IS for PKA (82/530) is popular and stocks are declining rapidly, therefore necessitating calibration of a replacement. A Ph. Eur. BRP is needed, as PKA control on the finished product is part of the Official Control Authority Batch Release (OCABR) of Human Albumin. The current IS, 82/530 is a 5 per cent albumin solution spiked with purified PKA. However, during planning stages it was decided that the replacement IS (and BRP) should be made from a 20 per cent albumin preparation containing a significant level of PKA as the current IS is used to measure PKA in albumin and high levels are more likely to be encountered in more concentrated 20 per cent solutions. A suitable material was sourced by the EDQM and filled into ampoules at NIBSC and vials by the EDQM. Both preparations were included in the collaborative study that involved 31 laboratories from 17 countries. Another important goal of this study was to investigate the influence of the prekallikrein substrate (PKS) on PKA determination in albumin solutions following earlier concerns that variability amongst PKS prepared in-house could significantly affect PKA determinations. Laboratories were requested to perform their routine assays following Ph. Eur. guidelines and recommendations on doses, replication and randomization were also provided to study participants. Participants were requested to use material A (the current IS, 82/530) to perform at least 4 assays to determine PKA levels in sample B (NIBSC ampouled material, candidate IS, 02/168), sample C (EDQM material in vials candidate Ph. Eur. BRP Batch 1), and sample D (an ampouled preparation of 2.5 per cent albumin containing a lower level of PKA). A commercial substrate was provided for participants to perform half the assays and the remaining assays were to be performed using the laboratories' in-house substrate (where available). Collation of participants' results showed that samples B and C had the same level of PKA of 29 IU/ampoule, the concentration anticipated from development studies. Importantly, there was no significant difference between the PKA level obtained using the commercial substrate provided and the laboratories' own in-house substrate. Previous observations on lyophilized preparations of PKA indicate that the enzyme is very stable. Detailed investigations conducted in this study show that the PKA in albumin used to make samples B and C is very stable and suitable for long-term storage as a reference material.

Collaborative study for the calibration of the Ph. Eur. prekallikrein activator in albumin BRP batches 4, 5 and 6.

An international collaborative study was organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe) to calibrate replacement batches for the current European Pharmacopoeia (Ph. Eur.) prekallikrein activator (PKA) in albumin biological reference preparation (BRP), whose stocks were dwindling. The study was run in the framework of the Biological Standardisation Programme (BSP) of the Council of Europe and the European Union (EU) Commission. Twenty three laboratories from official medicines control authorities and manufacturers in Europe and outside Europe took part in the study. Three candidate replacement batches were produced from the same material as the one used for the World Health Organization (WHO) 2(nd) International Standard (IS) for PKA in albumin (02/168) and the Ph. Eur. PKA in albumin BRP batches 1, 2 and 3. Participants were requested to evaluate the candidate batches against the current WHO IS using their routine assay method. The Ph. Eur. PKA in albumin BRP batch 3 (BRP3) was also included in the test panel to ensure the continuity of the consecutive BRP batches. The study confirmed the stability of the PKA content of the current BRP3. The candidate batches were found to be comparable. Previous data on the starting material support its high stability. Thermal stress study on the candidate batches confirmed the stability of their PKA activity. The Commission of the Ph. Eur. officially adopted in November 2013 the 3 candidate batches as Ph. Eur. PKA in albumin BRP batches 4, 5 and 6 with an assigned content of 38 IU/vial. The activity of the 3 new batches of Ph. Eur. PKA in albumin BRP will be regularly monitored.

Risk factors for severe bacterial infections after valve replacement and aortocoronary bypass operations: analysis of 246 cases by logistic regression.

Risk factors for severe bacterial infections, that is, deep sternal wound infection, pneumonia, septicemia, and prosthetic valve endocarditis, were evaluated in 246 consecutive patients undergoing valve replacement (N = 84) or aortocoronary bypass operation (N = 162). Multiple logistic regression analysis was applied to determine the ability of putative risk factors to predict infection. The risk factors considered were age, sex, diabetes mellitus, duration of cardiopulmonary bypass (CPB), duration of operation, amount of blood restored on the day of operation, repeat thoracotomy for bleeding, intraaortic balloon pumping, reoperation, emergency operation, and the professional status of the surgeon. Severe infections occurred in similar frequency after valve replacement (8/84; 9.5%) and aortocoronary bypass (11/162; 6.8%). For patients who had a bypass procedure, repeat thoracotomy was the only factor significantly associated with infection (p = 0.0004). However, the classification analysis revealed that this variable alone is too unspecific for a reliable prediction. Univariate analysis indicated that restoration of more than 2,500 ml of blood (p = 0.0001), reoperation (p = 0.0821), duration of operation (p = 0.0061), duration of CPB (p = 0.0318), and intraaortic balloon pumping (p = 0.0281) were associated with infection following valve replacement. A model with three variables emerged from the multiple logistic regression: after correction for blood restoration, reoperation, and duration of CPB, no other variable was of additional predictive value. For patients who underwent valve replacement, the model performed well in predicting complications. The classification analysis revealed a high correspondence between observed and predicted instances of infection: it correctly predicted 75% of the patients with infection and 96% of those without infection.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of procarbazine (MIH) on the induction of prophage lambda in Escherichia coli K12 and toxic effects on Salmonella typhimurium.

Natulan R (MIH, procarbazine) was tested for its ability to induce prophage lambda in Escherichia coli GY5027. E. coli Gy4015 served as indicator strain. A weak phage-inducing effect was observed at concentrations from 2 to 12 mg/plate in presence of S9 prepared from rats. This effect was found not to be due to the formation of hydrogen peroxide. It was confirmed that, even at the same high concentrations, no mutagenic effect can be detected with the Ames test in strains TA98 and TA100 of S. typhimurium. However, a toxic effect was observed in presence of S9 in S. typhimurium.

[Laparoscopic cholecystectomy as a suitable procedure for patients with cardiopulmonary risk factors?]. / Ist die laparoskopische Cholezystektomie das geeignete Verfahren für kardiopulmonale Risikopatienten?

There is considerable debate whether or not the laparoscopic technique for cholecystectomy supersedes conventional procedures in patients with pre-existing cardiopulmonary disease. Hemodynamic stress and CO2 absorption from the peritoneum can have a negative effect on intraoperative safety. On the other hand, a more rapid recovery of lung function and a shorter stay in hospital are the obvious advantages. 74 patients were investigated in our study: 54 with a low cardiopulmonary risk (group 1, ASA classes I or II) and 20 high risk patients belonging to ASA class III (group 2). Series of blood-gas samples were drawn from an arterial catheter and the respiratory parameters and blood gas values measured before and at the end of the CO2-insufflation period were compared. No dangerous rise in paCO2 or decrease in pH occurred with the ventilation method used in this study (Ti:Te = 1:1, PEEP = 5 mbar, Rf = 10/min modification of the tidal-volume according to the measured paCO2 and ventilation with an O2/air mixture). No significant changes in arterial O2 saturation compared with baseline values occurred and values remained within the physiological range. We conclude that excessive intraoperative paCO2 increase can be avoided by modification of the ventilation procedure and that laparoscopic cholecystectomy is an advantageous technique in the patient with cardiopulmonary disease.

Postoperative hemodynamic and thermoregulatory consequences of intraoperative core hypothermia.

STUDY OBJECTIVE: To evaluate the postoperative hemodynamic and thermoregulatory consequences of intraoperative core hypothermia. DESIGN: Prospective, randomized clinical trial. SETTING: Operating room and postanesthesia care unit of a university hospital. PATIENTS: 74 healthy, ASA status I, II, and III patients (average age 58 yrs) undergoing elective colon surgery. INTERVENTIONS: Patients were randomly assigned to be kept normothermic or approximately 2.5 degrees C hypothermic during surgery. Anesthesia was maintained with isoflurane, nitrous oxide, and fentanyl. Postoperatively, surgical pain was treated with patient-controlled analgesia (PCA) opioid. MEASUREMENTS AND MAIN RESULTS: An observer blinded to group assignment and core temperatures evaluated shivering, thermal comfort, surgical pain, heart rates (HRs), and blood pressures (BPs) during the first six postoperative hours. Morphometric characteristics, oxygen saturation, fluid balance, PCA-administered opioid, and visual analog pain scores were comparable in the two groups. Hypothermic patients felt uncomfortably cold during recovery, and their postoperative core temperatures remained significantly less than in the normothermic patients for more than four hours. Peripheral vasoconstriction and shivering were common in the hypothermic patients but rare in those kept normothermic. HRs and BPs were comparable in the two groups. CONCLUSIONS: These data confirm that the effects of intraoperative hypothermia on postoperative HR and BP are modest in relatively young, generally healthy patients. In contrast, intraoperative hypothermia caused substantial postoperative thermal discomfort, and full recovery from hypothermia required many hours. Delayed return to care normothermia apparently resulted largely from postoperative thermoregulatory impairment.

An international collaborative study to replace the 1st international standard for prekallikrein activator.

BACKGROUND AND OBJECTIVES: The aim of this study was to replace the 1st International Standard (IS) for prekallikrein activator (PKA) (code 82/530) with a new IS and European Biological Reference Preparation (BRP). The new standards were freeze dried 20% albumin solution containing PKA, the same solution that is tested using these standards. Aspects of the methodology for PKA determination were also examined as part of this study. MATERIALS AND METHODS: A batch of 20% albumin containing approximately 30 IU/ml was donated by a manufacturer of blood products and dispensed into ampoules at the National Institute for Biological Standards and Control (NIBSC) to create the candidate IS (02/168, sample B in the study) and at the European Directorate for the Quality of Medicines (EDQM) to create the candidate BRP (sample C in the study). The concentration of PKA in these preparations was determined in an international collaborative study involving 31 laboratories from 17 countries worldwide in comparison with the 1st IS for PKA (82/530) containing 85 IU of PKA per ampoule. Participants were requested to perform their own in-house method, based on the current Ph. Eur. monograph for determination of PKA in albumin solutions. Participants were provided with sufficient samples to perform two or three assays and were asked to use their local prekallikrein substrate (PKS) and also to use a commercial PKS provided as part of the study, in order to investigate the importance of the source of PKS on the final potency values. RESULTS: Samples B and C emerged with identical PKA concentrations of 29 IU/ml, very close to the expected value. This figure was determined using a variety of statistical methods, with the participants' own calculated values and values calculated centrally at the EDQM using raw data. The value of 29 IU/ml was consistent and independent of the method of calculation, although interlaboratory variability was more sensitive to the statistical analysis method. There was no statistically significant difference in mean potencies when comparing results with the laboratories' own local substrate and the substrate provided for the study. All stability studies indicate that these lyophilized preparations of PKA in 20% albumin are extremely stable. CONCLUSIONS: Samples B and C were established as the 2nd IS (code 02/168) and PKA activator in albumin BRP batch 1 (Y0000263), respectively, with a potency of 29 IU per ampoule. Results from this study indicate that testing for PKA in albumin may be less sensitive to the source of PKS than previously feared. The study highlights a number of methodological issues that may need revising in the Ph. Eur. general chapter 2.6.15.

[The critical care patient in the operating room]. / Der Intensivpatient im Operationssaal.

ICU patients can undergo elective or emergency surgery. Optimising the patient and arranging for the necessary blood components is as important as the fully monitored transport to the OR. Monitoring usually includes radial artery and vena cava access routes, pulmonary artery catheters help to check on oxygen transport parameters and cardiac output. Echocardiography is a new feature to determine cardiac volumes and left ventricular function as well as possible regional ischaemia. Anaesthesia induction can be performed using thiopentone along with diazepam and opioids. In shocked patients ketamine helps to prevent further drop of blood pressure. Propofol can also be employed for maintenance of anaesthesia. For muscle relaxation succinylcholine is the agent of choice if crush intubation is necessary. Atracurium and vecuronium should be used according to their specific route of elimination, although there can be interaction with antibiotics or adrenergic blockers. To ventilate the patient a mixture of oxygen in air might be useful, since nitrous oxide might be determined to blood cell formation and may distend gas-containing cavities. With the aid of positive end expiratory pressure FiO2 should be kept at a minimum, respiratory rate and inspiratory-expiratory ratio can keep ventilation pressures within an acceptable range and ensure CO2 excretion. Volume losses will be replaced mainly with Ringer's lactate, of which it takes four times the amount of colloidal replacement solutions which have the side effects of blood-borne infection and anaphylaxis. Fresh frozen plasma, platelets and erythrocytes might be necessary if coagulation parameters or oxygen transportation warrant it.(ABSTRACT TRUNCATED AT 250 WORDS)

[Does gelatin as a blood substitute selectively depress plasma fibronectin? A clinical randomized study]. / Senkt Gelatine als Blutersatzmittel selektiv das Plasmafibronectin? Eine klinische randomisierte Studie.

In 18 adult patients, in a randomized way, 15 ml/kg of blood were replaced either by gelatin 5.5 pc or serum protein solution. 0,5, 4 and 24 h later there was only a significant difference between the two groups in total protein and serum albumin. The low molecular weight infection related proteins alpha-1-antitrypsin, immunoglobulin G and antithrombin III, as well as the high molecular weight proteins immunoglobulin M, plasma fibronectin and alpha-2-macroglobulin were at no time significantly different between the two groups. It is concluded that gelatin as a plasma substitute does not impair the opsonising effect of plasma fibronectin upon the reticuloendothelial system.

[Administration of glucose 33 p.c. with added high doses of insulin within a scheme of early total parenteral alimentation to patients with shock-related excessive caloric demand (author's transl)]. / Verabreichung hochprozentiger Glucose mit grossen Insulindosen im Rahmen einer frühzeitigen totalen parentalen Ernährung bei Patienten mit schockbedingtem übersteigerten Kalorienbedarf

40 patients, who had been admitted to the ICU in a stage of shock were given glucose 33 p.c. with added high doses of insulin, administered within a scheme of early total parenteral alimentation, along with fat emulsions and aminoacid solutions. It is demonstrated that this type of nutrition is able to improve metabolisation of glucose in a phase of impaired glucose utilisation following shock. The duration of reduced glucose utilisation is 5-10 days during which period increased addition of insulin (24-18 U insulin/50 g glucose) is advisable. After this time the action of endogenous insulin was improved to such an extent that the added insulin could be reduced to 12 U insulin/50 g glucose up to the third week and later (up to 49 days) to 8 U insulin/50 g glucose.

[The in vitro influence of dehydrobenzperidol (droperidol) on lymphocyte transformation (author's transl)]. / Die Beeinflussung der Lymphocytentransformation durch Dehydrobenzperidol (Droperidol) in vitro

Droperidol, an agent which is used in neurolept anaesthesia was tested in vitro for its effect upon the lymphocyte transformation test. Using peripheral blood of healthy volunteers droperidol was added simultaneously with PHA (phytohaemagglutinin) respectively after the lymphocytes had been incubated with PHA already for a period of 47 hours. Lymphocyte transformation was not impeded significantly when the first method was used, when clinically comparable concentrations were administered. When droperidol was added after PHA even lower concentrations caused an inhibition. The significance of these different modes of testing is discussed. It is concluded from these results that droperidol in clinical concentrations as used in Neurolept anaesthesia does not have a distinct and lasting influence upon lymphocyte transformation and thus has no considerable immunosuppressive effects.

[Nifedipine and vecuronium bromide. How does a patient treated with calcium antagonists react to nondepolarizing muscle relaxants? Brief scientific communication]. / Nifedipin und Vecuroniumbromid. Wie reagiert der mit Ca-Antagonisten behandelte Patient auf nichtdepolarisierende Muskelrelaxantien? Kurze wissenschaftliche Mitteilung.

The muscle-relaxation reactions of Ca-antagonist (nifedipine) pretreated patients and a control group (5 in each group) were observed after administration of vecuronium bromide using the "priming principle." Twitch depression induced by the "priming dose" of vecuronium bromide (20 micrograms/kg body weight and T4/T1 ratio in the Ca-antagonist-treated patients (35 +/- 13% and 0.42 +/- 0.14%, respectively), was significantly different (P less than 0.01) when compared with the control group (1.2 +/- 2.7% and 0.75 +/- 0.15%). Similarly, the onset time to maximum blockade after the intubating dose of vecuronium bromide (60 micrograms/kg body wt.) was significantly shorter in the nifedipine group (40 +/- 21 s) when compared with the controls (100 +/- 17 s). The duration of the effect observed clinically (until 25% recovery) in the nifedipine group 32.9 +/- 7.3 min versus 25 +/- 8.15 min was enhanced; however, the difference between the treated group and the control group was not significant.

[Arterial baroreflex in intravenous anesthesia and assisted spontaneous respiration]. / Arterieller Baroreflex bei intravenöser Narkose und assistierter Spontanatmung.

Effects of a combined intravenous anaesthesia on the baroreceptor control of the circulation were determined in 8 healthy, unpremedicated patients, 18-50 years of age, scheduled for minor surgical procedures. The baroreflex was studied in response to brief hypotension with nitroglycerin (1-10 micrograms/kg i.v.) and quantified using the method described by Smyth, Sleight and Pickering (1969). The latter linearly correlates measurements of systolic blood pressure and the succeeding pulse interval, as obtained from recordings of the electrocardiogram. Responses in the conscious state were compared with those after administering diazepam (0.2 mg/kg i.v.), etomidate (8-20 mg i.v.) and fentanyl (0.015-0.025 mg/kg i.v.) while the patients were breathing a mixture of oxygen and nitrous oxide (1:2) during mechanically assisted ventilation. Anaesthesia led to a decrease in heart rate (17 +/- 3%) together with a slight but significant reduction in mean arterial pressure (15 +/- 4%). The mean slopes and correlation coefficients in the conscious and anaesthetized states were y = 426 + 2.33 X; r = 0.56; p less than 0.05 and y = 663 + 2.16 X; r = 0.49; p less than 0.05, respectively. Thus, no significant difference of the function of the baroreflex was observed in the conscious and anaesthetized patients. It is concluded that in contrast to inhalational anaesthesia the employed combined intravenous anaesthesia with mechanically assisted ventilation does not change this important control mechanism of the circulation in man.

[Hemoconcentration caused by excessive intraoperative ascites production in ulcer bleeding]. / Hämokonzentration durch intraoperative exzessive Aszitesproduktion bei Ulkusblutung.

The estimation of the intraoperative fluid requirements can be particularly difficult in patients with compartmental disturbances, e.g. hepatic cirrhosis. The case history of a 41 year old female with a known history of liver cirrhosis is reported who underwent emergency surgery due to upper gastro-intestinal bleeding. In order to maintain hemodynamic stability preoperative blood loss was replaced with fresh blood. During the operation 4 liters of bank and fresh blood with 5 liters of erythrocyte-free fluids were administered. After operation reliable clinical signs of hypovolemia and a marked increase in hematocrit were noted. The severe hemoconcentration was explained by excessive fluid shifts away from the intravascular compartment since a total amount of 10 liters of ascites was collected for the next 24 hours. This overproduction can be related to portal hypertension, hypoalbuminemia and activation of the renin-angiotensin-aldosterone system.

[Method of determining glomerular filtration rate and extracellular fluid volume in the perioperative phase]. / Zur Methodik der Bestimmung von glomerulärer Filtrationsrate (GFR) und extrazellulärem Flüssigkeitsvolumen (EZF) in der perioperativen Phase.

In the course of an investigation concerning the renal response in abdominal surgery, we paid special attention to the precision of determination of the glomerular filtration rate (GFR) and extracellular fluid volume (ECF). The influence of the applied mathematical model on calculation using slope techniques was examined. ECF and GFR were measured by single injection of the radioactive tracer 51Cr-EDTA; plasma samples were taken during the first 4 h postinjection. The results were computed according to the compartmental and noncompartmental model. The correlation between two-compartmental and noncompartmental GFR and ECF values was highly significant. However, values calculated from two-compartmental model were significant lower (p less than 0.01) and differences up to 20% were observed. Calculating ECF by the most widely used approximative method (assuming an early equilibrium between the extra- and intravascular part of ECF) yields incredible high values and correlation to other methods was poor. Based on our data, we conclude that GFR and ECF values obtained by compartmental analysis depend on flow rates between the theoretical compartments. Also the use of two or three exponential components for the plasma curve in the course of noncompartmental analysis (as done by most authors) is not any better than compared conventional compartmental analysis. Noncompartmental analysis should be preferred especially when small changes in ECF and GFR are observed, as it is the more accurate.