The influence of cell design on the uniformity of batch ohmic heating of a solid foodstuff was examined. Various ways of minimising heat loss from the cell surface including insulation or providing supplementary heat via a heating belt or panel were assessed but discarded in favour of housing the cell in a hot air cabinet maintained at 80 °C and eliminating the surrounding cell body. Various electrode materials and designs were evaluated prior to opting in favour of platinised titanium electrodes of minimal practicable thickness (1 mm). The final system developed involved the use of a combined ohmic/convection heating with the food stuff contained in a plastic casing pressurised between two spring-loaded electrodes. Under optimised conditions a maximum overall temperature variation of 12.1 °C within the product was achieved after 150 s which was reduced to 8.6 °C after 3 min standing time.

To produce a safe cooked food product it is necessary to ensure a uniform heating process. The aim of this study was to develop a mathematical model of a solid food material undergoing heating in a cylindrical batch ohmic heating cell. Temperature profiles and temperature distribution of the ohmic heating process were simulated and analysed via experimental and mathematical modelling which incorporated appropriate electromagnetic and thermal phenomena. Temperature profiles were measured at nine different symmetrically arranged locations inside the cell. The material was ohmically heated imposing a voltage of 100V, while electrical field and thermal equations were solved for experimental and theoretical models by the use of FEMLAB, a finite element software. Reconstituted potato was chosen to represent a uniform solid food material and physical and electrical properties were determined prior to the experiment as a function of temperature. The simulation provided a good correlation between the experimental and the mathematical model. No cold spots within the product were detected but both experimental and model data analysis showed slightly cold regions and heat losses to the electrode and cell surfaces. The designed model could be used to optimize the cell shape and electrode configurations and to validate and ensure safe pasteurisation processes for other solid food materials.

Temperature mapping during batch ohmic heating is a challenging but critically important task. It is essential to be able to monitor temperature changes at various, selected locations within a food to ensure a safe cooking process. Thermocouple probes of various designs and sizes were assembled and evaluated in order to develop thin, robust, fully insulated and rapid measurement devices. The response time of each probe was measured, and the accuracy and precision of the thermocouple probes were evaluated using established procedures. The most satisfactory thermocouple probe for application in a batch ohmic heating system was found to be a triple-point probe with a fully insulated stainless steel sheath having an outer diameter of 2mm, an internal diameter of 1.5mm and a response time of 0.6s.

AIMS:This study constituted the first administration of the oral platelet inhibitor, sibrafiban, to humans. The aim was to investigate the pharmacokinetics and pharmacodynamics of Ro 44-3888, the active principle of sibrafiban, after single ascending oral doses of sibrafiban. Particular emphasis was placed on intersubject variability of the pharmacokinetic and pharmacodynamic parameters of Ro 44-3888.METHODS:The study consisted of three parts. Part I was an open ascending-dose study to determine target effect ranges of sibrafiban. Part II, a double-blind, placebo-controlled, parallel-group study, addressed the intersubject variability of pharmacokinetic and pharmacodynamic parameters of the active principle at a sibrafiban dose achieving an intermediate effect. Part III was a double-blind, placebo-controlled, ascending-dose design covering the complete plasma concentration vs pharmacodynamic response curve of sibrafiban.RESULTS:At sibrafiban doses between 5 mg and 12 mg, the pharmacokinetics of free Ro 44-3888 in plasma were linear whereas those of total Ro 44-3888 were non-linear because of the saturable binding to the glycoprotein IIb-IIIa receptor. Saturation of the GP IIb-IIIa receptor was reached at plasma concentrations of 15.9 ng ml-1. At sibrafiban doses up to 2 mg, ADP-induced platelet aggregation was inhibited by 50%, whereas the inhibition of TRAP-induced platelet aggregation was about 20-30%. At the higher doses, ADP-induced platelet aggregation was almost completely inhibited while a clear dose-response could be observed with TRAP-induced inhibition of platelet aggregation at sibrafiban doses of 5 to 12 mg. Ivy bleeding time increased very steeply with dose with a significant prolongation observed at doses of 5 to 7 mg of sibrafiban (5-7 min, >30 min in one case). At a sibrafiban dose of 12 mg, the stopping criterion for dose escalation (prolongation of the Ivy bleeding time >30 min in three out of four subjects per dose group) was reached. The interindividual coefficients of variation of the integrated pharmacokinetic and pharmacodynamic parameters (AUC and AUE) were below 20%, thus lying well within the pre-set level of acceptance.CONCLUSIONS:With a low intersubject variability of its pharmacokinetic and pharmacodynamic parameters, linear pharmacokinetics and pharmacodynamic effects closely related to its plasma concentrations, Ro 44-3888 has good pharmacological prerequisites for a well controllable therapy of secondary prevention of arterial thrombosis in patients with acute coronary syndrome.

Boiling heat transfer on a miniature heater has been studied under microgravity conditions during the IML 2 Space Shuttle Mission in 1994. These experiments are simulations for the application of the direct cooling of small electronic devices by boiling heat transfer in space. This becomes very important due to high thermal loads of modern electronic components. The results of this investigations are: Even at microgravity the heat transfer coefficients are very high and are even higher compared with other heater geometry. A remarkable influence of the gravity on the nucleate boiling heat transfer could not be observed, only in the transition and film boiling region a reduction up to 50 % was found. Several boiling modes have been observed during the experimental runs depending on the subcooling of the liquid, the liquid state, and the overall heat flux. Surface tension, wetting behavior, coalescence processes, the momentum of bubble formation, and thermocapillary convection play the most important role in boiling. The general statement can be made: boiling can be applied for cooling processes in microgravity.

Petroclival meningiomas are complex, deep-seated lesions related to many critical neurovascular structures. We present the case of a 44-year-old woman who had presented with a history of severe facial pain, hearing loss, and tinnitus on the left side, associated with left facial hypoesthesia (Video 1). Preoperative magnetic resonance imaging demonstrated a mass highly suggestive of a left petroclival meningioma. Considering the worsening symptoms and important mass effect, microsurgical resection using the posterior petrosal approach was performed. Mastoidectomy was performed first, followed by craniotomy encompassing both posterior and middle cranial fossae. The posterior fossa and middle fossa dural incisions were connected, coagulating and sectioning the superior petrosal sinus. Next, the tentorium was cut all the way toward the incisura, with care to preserve the fourth nerve in the last cut. After completion of the tentorium incision, the presigmoid space increased. The lesion was totally resected using microsurgical techniques, with the aid of an ultrasonic aspirator to debulk the mass and allow for its circumferential dissection. Postoperative magnetic resonance imaging demonstrated complete tumor resection. The patient presented with improvement of symptoms and no new neurological deficit during follow-up. Skull base approaches, such as the posterior petrosal approach, are useful for successfully treating challenging lesions such as the one presented, with low morbidity. Laboratory training is essential to be familiarized with the complex intraoperative neuroanatomical nuances. The patient provided written informed consent for the report of her case and operative video. The anatomical images were provided courtesy of the Rhoton Collection, American Association of Neurological Surgeons/Neurosurgical Research and Education Foundation.

The boiling heat transfer on a miniature heater has been measured under microgravity conditions during the IML 2 mission and under earth gravity after the mission in 1994. These experiments are simulations for the direct cooling of small electronic devices by boiling heat transfer, which becomes very important due to high thermal loads of modern electronic components.

Bei freien Grenzflächen spielt die thermokapillare Konvektion eine nicht zu vernachlässigende Rolle auf den Wärmetransport. In zwei Experimenten wird deren Einfluß aufgezeigt. In Silikonölen verschiedener Viskosität mit thermisch stabiler Schichtung werden Luftblasen eingebracht und das durch die thermokapillaren Kräfte gegen den Auftrieb erzeugte Geschwindigkeitsfeld vermessen. In einem zweiten Experiment wird die Erhöhung des Wärmeübergangs durch eine Luftblase an einem beheizten Draht gemessen. Trotz kleiner Berührungsfläche kann der Wärmeübergang gegenüber dem Draht ohne Blase verdoppelt werden, was der zusätzlichen Marangoni-Konvektion zuzuschreiben ist. In Wasser wurde dieser Effekt nicht beobachtet, hier wurde durch die Luftblase der Wärmeübergang um 30% reduziert.

The thermocapillary convection on free surfaces is an important mechanism for heat transfer, it is demonstrated in two experiments. Silicon-oil of various viscosity is used as experimental liquid. In the thermal stable stratified liquid air bubbles were injected. Around the bubbles velocity profiles, induced by the thermocapillary force against the buoyancy force were measured. In the second experiment the enhancement of heat transfer induced by air bubbles touching a heated wire is investigated in various liquids. In spite of the small contact area between the bubble and the wire the increase of heat transfer was more than twice of the wire without bubble which is attributed to the Marangoni convection. Using water this enhancement could not be observed. At the bubble the free convection from the wire was hindered and the heat reduced by 30%.

A highly sensitive capillary gas chromatographic method was developed to determine plasma levels of a novel partial benzodiazepine receptor agonist in man following the very low therapeutic doses required for anxiolysis. The compound was isolated from plasma by liquid-liquid extraction at basic pH, converted into the ethyl ester analogue by a two-step procedure, separated from plasma constituents by capillary gas chromatography and quantified by means of nitrogen-selective detection. Because of the thermolabile tert.-butyl ester function, the agonist could not be gas chromatographed without degradation. Formation of the far more stable ethyl ester analogue was achieved by treatment with hydrogen chloride in ethanol, followed by an ethylation step with diazoethane. The high sensitivity of the new method (about 100 pg/ml, using 1-ml plasma specimens) allowed the monitoring of plasma levels of the agonist for up to 8 h (about three elimination half-lives) after a single 0.1-mg oral dose to human volunteers. The practicability of the procedure was demonstrated by the analysis of more than 600 plasma samples from clinical studies performed with human volunteers.

This study was performed to establish an experimental method for the investigation of interactions between ethanol and drugs under predictable and controlled conditions. The model was tested with flumazenil (Ro 15-1788), a short-acting benzodiazepine antagonist with an elimination half-life of 1 h. Six healthy volunteers (5 males, 1 female) were administered ethanol by intravenous infusion with stepwise changing rates. The infusion rates were adapted to each subject on the basis of individual disposition parameters of ethanol, which were derived from preceding short-term infusions of 120 min duration (1.0 mg/kg in males, 0.8 mg/kg in the female). This two-step procedure led to individual ethanol plasma levels between 1.47 ± 0.04 and 1.71 ± 0.03 g/L, which were reached after 2.5 h and thereafter maintained over another 6 h. Within the period of constant ethanol levels, single doses of flumazenil and placebo, respectively, were injected intravenously as a bolus (2 min) in a double-blind fashion according to a randomized two-way crossover design. Three subjects received a dose of 0.10 mg/kg of flumazenil, and the remaining three subjects received a dose of 0.20 mg/kg. Evaluation of the plasma concentration time curves of flumazenil did not reveal evidence of an effect of ethanol on the pharmacokinetics of this drug.

A sensitive and specific HPLC-assay was developed for the determination of the benzodiazepine antagonist ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-[1,5-a] [1,4]benzodiazepine-3-carboxylate (Ro 15-1788; envisaged INN: flumazepil) in plasma. Ro 15-1788 and the internal standard were extracted from plasma at a basic pH, separated from coextracted plasma components on a reversed-phase column and quantitated by means of a UV detector. Ro 15-1788 was extracted quantitatively from plasma in the concentration range 25.6 to 300 ng/ml. The sensitivity limit was about 10 ng/ml plasma using a 1-ml specimen. The method was shown to be specific with respect to several benzodiazepines and their main metabolites. The method was successfully applied to pharmacokinetic studies in man after oral and intravenous administration of Ro 15-1788.

A specific and highly sensitive gas-liquid chromatographic method was developed for the determination of oxiconazole in rat, dog, and human plasma. The compound and its internal standard were extracted from plasma at basic pH with n-hexane-isoamyl alcohol (98:2, v/v), gas chromatographed on 3% SP-2250/Supelcoport (80-100 mesh) and quantified by means of an electron-capture detector. Oxiconazole was extracted almost quantitatively from plasma in the concentration range 10-5000 ng/ml. The sensitivity limit was about 1 ng/ml, using a 1-ml specimen. The method was applied to 13-week tolerance studies in dogs and rats in order to follow oxiconazole concentrations in plasma after oral administration of the compound. The assay was sensitive enough to measure precisely the small amounts of unchanged compound in plasma after intravaginal application of labelled oxiconazole to human volunteers.

Eggs of penguins can be used to monitor indirectly the pollution of the antarctic and sub-antarctic marine environment. The different penguin species are located in defined circumpolar areas, allowing an easy regional monitoring of persistent xenobiotics in the Antarctic.