Hydrogen-bond equilibria and lifetimes in a monohydroxy alcohol.

Dielectric loss spectra covering 13 decades in frequency were collected for 2-ethyl-1-hexanol, a monohydroxy alcohol that exhibits a prominent Debye-like relaxation, typical for several classes of hydrogen-bonded liquids. The thermal variation of the dielectric absorption amplitude agrees well with that of the hydrogen-bond equilibrium population, experimentally mapped out using near infrared (NIR) and nuclear magnetic resonance (NMR) measurements. Despite this agreement, temperature-jump NIR spectroscopy reveals that the hydrogen-bond switching rate does not define the frequency position of the prominent absorption peak. This contrasts with widespread notions and models based thereon, but is consistent with a recent approach.

Heterologous expression and characterization of choline oxidase from the soil bacterium Arthrobacter nicotianae.

In the course of a microbial screening of soil samples for new oxidases, different enrichment strategies were carried out. With choline as the only carbon source, a microorganism was isolated and identified as Arthrobacter nicotianae. From this strain, a gene coding for a choline oxidase was isolated from chromosomal DNA. This gene named codA was cloned in Escherichia coli BL21-Gold and the protein (An_CodA) heterologously overexpressed as a soluble intracellular protein of 59.1 kDa. Basic biochemical characterization of purified protein revealed a pH optimum of 7.4 and activity over a broad temperature range (15-70 degrees C). Specific activities were determined toward choline chloride (4.70 +/- 0.12 U/mg) and the synthetic analogs bis(2-hydroxyethyl)-dimethylammonium chloride (0.05 +/- 0.45 x 10(-2) U/mg) and tris-(2-hydroxyethyl)-methylammonium methylsulfate (0.01 +/- 0.12 x 10(-2) U/mg). With increasing number of oxidizable groups, a significant decrease in activity was noted. Determination of kinetic parameters in atmorspheric oxygen resulted in K (M) = 1.51 +/- 0.09 mM and V (max) = 42.73 +/- 0.42 mU/min for choline chloride and K (M) = 4.77 +/- 0.76 mM and V (max) = 48.40 +/- 2.88 mU/min for the reaction intermediate betaine aldehyde respectively. Nuclear magnetic resonance spectroscopic analysis of the products formed during the enzyme reaction with choline chloride showed that in vitro the intermediate betaine aldehyde exists also free in solution.

PCL-PGLA composite tubular scaffold preparation and biocompatibility investigation.

The objective of this paper was to fabricate a biodegradable tubular scaffold for small diameter (d<6 mm) blood vessel tissue engineering. The tube scaffold needed a porous wall for cell attachment, proliferation and tissue regeneration with its degradation. A novel method given in this paper was to coat a porous layer of poly (epsilon-caprolactone) (PCL) on the outside of a poly (glycolic-co-lactic acid) (PGLA with GA:LA=90:10) fiber braided tube to give a PCL-PGLA composite. The PGLA tube was fabricated using a braiding machine by inserting a Teflon tube with the desired diameter in center of the 20 spindles, which are the carriers of PGLA fibers. Changing the diameter of the Teflon tube can vary the inner diameter of a braided PGLA tube. Thermally induced phase separation method was used for PCL solution coating on the surface of the PGLA braided tube. Controlling the polymer concentration, non-solvent addition and quenching temperature generated the pore structures, with pore sizes ranging from 10-30 microm. The fibroblast cells were seeded on the tubular scaffold and cultured in vitro for the biocompatibility investigation. Histology results showed that the fibroblast cells proliferated on the interconnected pore of the PCL porous layer in 1 week.

[The role of public health service in prevention and control of infectious diseases in the Federal Republic of Germany. Tasks, structures and responsibilities--an overview]. / Rolle der Gesundheitsbehörden der Länder bei der Verhütung und Bekämpfung von Infektionskrankheiten. Aufgaben, Strukturen und Zuständigkeiten--eine Ubersicht.

The goal is to describe the structure of administration for the control of infectious diseases in the German states. Internationally there is an increasing risk of potentially global transmission of infectious diseases and therefore increasing need for improved control mechanisms which are viable locally, regionally and internationally. The international public health community must ensure that responses to infectious disease with a potential impact on more than one county entail concerted action, clear communication and decision making by diverse administration agencies. Given Germany's federal structure, the 16 states have differing protocols delineating responsibilities for infection control systems. This paper provides an overview, going into detail only with regard to the administration structure in Hesse. In 2001, the German law governing infectious disease control was amended and significantly expanded. With regard to protection of humans from infectious disease, each state must define its schedule of responsibilities on the resulting scope of duties. Each state in Germany has entrusted the local public health service at the county level with the responsibility for infection prevention and control. As a rule, at the state level both an expert agency and one or more district administration agencies have been installed; these work directly with the Ministry of Health at the state level. In addition to this, Hesse has established a "centre of competence for highly contagious diseases." In the event of an infectious emergency, this network provides special treatment of highly infectious patients and expertise for public health services and the Ministry of Health on a 24-h shift basis. In times of ongoing structural transformation, it is important to emphasize that expertise at the state level is not an alternative to maintaining enough specialised personnel in the public health services themselves. Specialized practitioners are needed to ensure professional and fast-acting responses, both for the prevention and control of infectious diseases.

Interference by cellular phones with permanent implanted pacemakers: an update.

AIMS: The aim of this study was to test pacemakers with feedthru filters for interference with a digital cellular telephone. METHODS: The study comprised 100 patients having their first pacemaker implantation between January 2001 and May 2003. A GSM-standard cellular phone was tested in the standby, dialing and operating mode against 23 single-chamber and 77 dual-chamber pacemakers. Continuous surface electrocardiograms, intracardiac electrograms, and marker channels were recorded when calls were made by a land phone to the cellular phone. RESULTS: In 2 patients we observed pacing inhibition with the cellular phone positioned directly above the pacemaker pocket. The unipolar and bipolar ventricular sensitivity setting was 0.25 mV in one dual-chamber pacemaker, and when we changed the sensitivity to 0.50 mV and higher no interference could be detected. The second inhibition occurred in a single-chamber pacemaker with unipolar and bipolar ventricular sensitivity setting of 0.5 mV, where a sensitivity change to 1.0 mV eliminated the interference. CONCLUSION: Anticipating a correct setting of ventricular sensitivity, currently available pacemakers equipped with feedthru filters do not show any interference with cellular phones. Since interference was only observed with sensitivity settings below 0.50 mV, we recommend that permanent programming of ventricular sensitivity should be set at 2.0 mV and higher.

Impact of tranexamic acid vs. aprotinin on blood loss and transfusion requirements after cardiopulmonary bypass: a prospective, randomised, double-blind trial.

INTRODUCTION: Aprotinin (AP) reduces blood loss and transfusions after cardiopulmonary bypass (CPB), but may sensitise patients and is expensive. Tranexamic acid (TA) has less side-effects, but data regarding its efficacy are controversial. The aim of our prospective, randomised, double-blind study was to compare the impact of AP vs. TA on drainage blood loss and transfusion requirements in patients undergoing first time CABG on CPB. MATERIALS AND METHODS: One hundred and twenty adult patients were randomised to receive either high-dose AP according to Hammersmith or a total of 2 g TA. Perioperative blood products were transfused in a standardised fashion. Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge. RESULTS: The data from 118 patients (TA: n = 58, AP: n = 60) who completed the study according to protocol were analysed. Blood loss at 24 h postoperation in TA patients was significantly higher (896 +/- 354 ml) as compared to AP patients (756 +/- 347 ml; p = 0.03). TA patients received 1.5 +/- 1.5 units of red blood cells (AP: 1.5 +/- 1.7, p = 1.0), 1.3 +/- 2.0 units of fresh frozen plasma (AP: 1.0 +/- 2.0, p = 0.38) and 0.5 +/- 1.4 units of platelets (AP: 0.2 +/- 0.7, p = 0.15). Clinical data, including perioperative myocardial infarction rate, acute renal failure, mechanical ventilation, hospital stay and mortality, were not significantly different between either group. CONCLUSION: Our data show a difference in blood loss between TA and high-dose AP. Although statistically significant, it has little clinical relevance, because perioperative transfusion requirements were similar for both groups. Thus, TA appears to be a cost-effective alternative to AP in primary CABG patients.

Patch-clamp recording in brain slices with improved slicer technology.

The use of advanced patch-clamp recording techniques in brain slices, such as simultaneous recording from multiple neurons and recording from dendrites or presynaptic terminals, demands slices of the highest quality. In this context the mechanics of the tissue slicer are an important factor. Ideally, a tissue slicer should generate large-amplitude and high-frequency movements of the cutting blade in a horizontal axis, with minimal vibrations in the vertical axis. We developed a vibroslicer that fulfils these in part conflicting requirements. The oscillator is a permanent-magnet-coil-leaf-spring system. Using an auto-resonant mechano-electrical feedback circuit, large horizontal oscillations (up to 3 mm peak-to-peak) with high frequency ( approximately 90 Hz) are generated. To minimize vertical vibrations, an adjustment mechanism was employed that allowed alignment of the cutting edge of the blade with the major axis of the oscillation. A vibroprobe device was used to monitor vertical vibrations during adjustment. The system is based on the shading of the light path between a light-emitting diode (LED) and a photodiode. Vibroprobe monitoring revealed that the vibroslicer, after appropriate adjustment, generated vertical vibrations of <1 microm, significantly less than many commercial tissue slicers. Light- and electron-microscopic analysis of surface layers of slices cut with the vibroslicer showed that cellular elements, dendritic processes and presynaptic terminals are well preserved under these conditions, as required for patch-clamp recording from these structures.

Second harmonic generation in the centrosymmetric antiferromagnet NiO.

In spite of the fact that inversion is a symmetry operation of both the crystalline and the magnetic lattice of NiO, second harmonic generation (SHG) has been observed below the Néel temperature. A spectroscopic study shows that the signal is due to combined magnetic-dipole and electric-dipole transitions between the (3d)(8) levels of the Ni(2+) ion in the crystal field. The SHG is resonant in both the incoming and the outgoing light waves and thus greatly enhanced. A quadratic coupling of the nonlinear polarization to the order parameter was found. This allows the investigation of individual domains.

Antidepressant drug use: differences between psychiatrists and general practitioners. Results from a drug utilization observation study with fluoxetine.

Between 1990 and 1993, a series of drug utilization observation studies with fluoxetine (Flx) were conducted in Germany in several waves. 3,158 patients treated by psychiatrists/neurologists (PN) and 15,601 patients treated by general practitioners/internists (GPI) were included; data collection at start and end of treatment focussed on diagnoses, symptoms, prescription, comedication, efficacy (CGI, Zung scale), and adverse events. Differences between PN and GPI patients were of major interest. For more than 90% of both the PN and the GPI cases. Fix was used for the indication of "depression", with a dosis of 20 mg/day. More PN patients (47%) than GPI patients (28%) were diagnosed as "endogenous"; GPI patients more often presented with first episodes (36 vs. 24%). "suicidal ideation" was less prominent compared to PN subjects (17 vs. 28%). Psychotropic comedication was regarded as necessary in 39% (PN) and 10% (GPI) of the cases. Early treatment termination because of "remission/major improvement" was observed in 13% (PN) vs. 21% (GPI) and because of "adverse events" in 11% (PN) vs. 3% (GPI) of the patients. At observation end, 53% (PN) vs. 74% (GPI) were rated as "symptom-free/markedly improved" (CGI); self-ratings reflected comparable results, marked improvements over time, but still PN/GPI differences at the end. "Suicidality" related to depression was more pronounced in the PN group at both points in time. 24% (PN) vs. 6% (GPI) of the cases reported "routine" adverse events, while in 2% (PN) and 1% (GPI) "serious" adverse events were observed. (For all the above comparisons p < 0.001 to < 0.0001.) These findings reveal that-under routine conditions handled by PNs and GPIs-Fix shows an efficacy and safety consistent with clinical trial data. The body of data suggests that PN patients present with more severe depression and more suicidality, require more comedication, and end up with a poorer outcome. Differences in the physicians' perception of psychiatric and somatic symptomatology and their treatment routines may also have something to do with the PN/GPI group differences observed.

An investigation of the representativity of neuropsychiatrists and their patients in a drug utilization observation study on fluoxetine.

This study presents a methodological approach to an expost facto investigation of sample bias in drug utilization observation (DUO) studies using the example of a DUO with the nontricyclic antidepressant fluoxetine. A total of 479 psychiatrists and neurologists and 2,401 patients were investigated. The purpose of the study was to judge the representativeness of our DUO sample for two populations: first, for all psychiatrics and neurologists prescribing fluoxetine or all patients being treated with fluoxetine in Germany and, second, for all psychiatrists and neurologists prescribing antidepressants or all patients being treated with antidepressants in Germany. Criteria for the representativeness test were physician variables (gender, size of community where practicing, federal state, age, volume of prescriptions) and patient variables (gender, age, prescription-related diagnosis, concurrent illnesses, concomitant medications). The study shows that the DUO sample can rightfully claim representativeness in the majority of parameters for the psychiatrists and neurologists prescribing fluoxetine and for the patients being treated with fluoxetine. There are more noticeable discrepancies with regard to the psychiatrists and neurologists in general and to the patients being treated with antidepressants in general. The methodological problems of pharmacoepidemiological investigation of representativeness are discussed.

Guidelines for the implementation of drug utilization observation (DUO) studies in psychopharmacological therapy. The "Phase IV Research" Task-Force of the Association for Neuropsychopharmacology and Pharmacopsychiatry (AGNP).

The task-force on Phase-IV-Research of the Association for Neuropharmacology and Pharmacopsychiatry (AGNP) has developed guidelines for the implementation of scientifically sound drug utilisation observation studies (DUO studies). These guidelines have been adopted by the executive committee as the position of the association. DUO studies are prospective pharmacoepidemiological studies, by which prescription, illness, and patient data of individual patients are collected without interference with the routine course of treatment. They can answer questions on the interaction of treatment modalities with positive and negative treatment outcome. Scientific standards require that there is a study protocol which describes the epidemiological, statistical, procedural, and quality assurance methodology and states who is responsible for what. As such studies can violate data protection regulations or can be used for sales instead of scientific purposes, consultation of an ethics committee is recommended.

Adverse events and tolerability of the combination of fluoxetine/lithium compared with fluoxetine.

Data from an intensive observational drug utilization study were analyzed to determine whether patients who received the combination of fluoxetine and lithium had more and different adverse events as compared with those receiving fluoxetine alone. In a matched cohort control design, we compared 110 patients per group. Results showed no significant difference in side effects between groups. Also, the incidence of "serotonergic" adverse events showed no significant differences between groups during the 7-week study period. In conclusion, the results show that the combination of fluoxetine/lithium is generally well tolerated in spite of a somewhat increased rate of minor side effects.

[An Experiment to calculate the theoretical temperature at the drill-cortical bone interface]. / Ein Versuch zur theoretischen Temperaturermittlung im Schneidbereich bei Bohrungen in kortikalem Knochen.

To date, analysis of temperature in the drill area of cortical bone have been limited to measurements with thermocouple systems at a certain distance from the drill hole. Many authors equate this temperature measurement with the drill--cortical bone interface temperature. In order show that there is a temperature difference, a drill hole was simulated with the aid of the "Finite Element Method". The interface temperature was calculated by the energy distribution. It was shown, that for "dry" and "watercooled" drilling, the drill hole temperature was 13 degrees C higher than the temperature measured with the thermocouple systems at a distance 0.5 mm of from the drill hole. In particular when using "watercooled" drills for bone and dental surgery, the temperature may be higher than the bone damage limit of 44 degrees C for lengthy and 50 degrees C for brief drilling.

Purification of photochemically active halorhodopsin.

We have developed a procedure for the purification of halorhodopsin in a photochemically active state. Solubilization of membranes from a bacteriorhodopsin-negative Halobacterium strain with octyl glucoside was followed by chromatography on hydroxylapatite and octyl-Sepharose gels. All steps were carried out in high-ionic-strength solutions. The procedure resulted in 270-fold enrichment with a 35% yield. The eluted pigment had an absorption maximum at 575 nm and an A280/A575 ratio of 2. On removal of the detergent by dialysis, the purified halorhodopsin was chemically bleached, regenerated with [3H]retinal, and reduced with cyanoborohydride. Such samples showed one main and one satellite band after staining or fluorography of NaDodSO4/polyacrylamide gels. The apparent molecular weight of the main band was 25,000. Purified halorhodopsin underwent a photocycle after excitation with pulsed laser light and showed a 9-nm blue shift (at neutral pH) on removal of chloride ion. The pigment also underwent a photoreversible shift at alkaline pH to a form absorbing maximally at 410 nm. All three reactions closely resembled those of membrane-bound halorhodopsin.

Exclusive formation of all-trans-phytoene by a colorless mutant of Halobacterium halobium.

A spontaneously occurring Halobacterium halobium mutant (strain W5002-1) was isolated which accumulated phytoene as the only C40 polyene. Its configuration was established as all-trans (7,8,11,12,7',8',11',12',-octahydro-psi,psi-carotene) by its chromatographic and spectral properties. Neither bacterioruberins (C50) nor retinal (C20) could be detected in this mutant strain. The biosynthetic pattern of isoprenoid compounds in this mutant strain confirms for the first time our conjecture that spontaneously arising H. halobium mutants can be isolated with defects in the carotenoid pathway and lends further support to our previous hypothesis suggesting all-trans-phytoene to be the precursor for more unsaturated carotenoids in halobacteria.

Na+ transport via Na+/H+ antiport in Halobacterium halobium envelope vesicles.

Using H. halobium cell envelope vesicles containing either bacteriorhodopsin plus Na+ pump, bacteriorhodopsin alone, Na+ pump alone, or no light-responsive pigment altogether, it could be shown that the large majority of light energized Na+ extrusion in these mutants is linked to bacteriorhodopsin and to protonmotive force, and therefore must be facilitated by a Na+/H+ antiporter. Thus, the recently discovered primary Na+ pump makes only a minor contribution to light-mediated Na+ flux. The activity of the Na+/H+ antiporter appears to be independent of the presence of any photoreactive pigments, since an artifical electron donor will drive rapid Na+ extrusion in all of the vesicle preparations tested.