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  • 1
    Electronic Resource
    Electronic Resource
    Biological effects of encapsulated insulin on transfected Chinese hamster ovary cells (1995)
    Springer
    Diabetologia 38 (1995), S. 180-186 
    Details
    ISSN: 1432-0428
    Keywords: Insulin pharmacology ; insulin metabolism ; oral administration ; dose-response relationship ; cultured cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Oral administration of insulin incorporated into the wall of isobutylcyanoacrylate nanocapsule to diabetic rats induces a long-lasting normalization of their fasting glycaemia. In this study, we examined the biological action of encapsulated insulin on DNA and glycogen syntheses in Chinese hamster ovary cells transfected with the human insulin receptor gene. In the 10−11 mol/l–10−9 mol/l concentration range, encapsulated insulin elicited responses comparable to those induced by native insulin: at 10−9 mol/l, the rates of glycogen and DNA synthesis were enhanced by factors 3 and 2.5, respectively. Encapsulated insulin at 10−7 mol/l evoked receptor desensitization although it did not induce receptor down-regulation and did not alter receptor recycling for up to 6 h. Chloroquine decreased the action of native insulin on glycogen synthesis, but did not affect the dose-response characteristics of encapsulated insulin. Acid-washing of the cells after 1 h of stimulation decreased maximal insulin responsiveness and provoked a dose response curve for encapsulated insulin similar to that of the native hormone. Direct measurement of effective insulin binding activity showed that encapsulated insulin (at 10−8 and 10−7 mol/l) was withdrawn from the incubation medium 5–8 times less efficiently than native insulin. These data are in agreement with previous results showing that the polymeric wall protects encapsulated insulin from degradation. Persistence of intact encapsulated insulin inside and outside the cell may result in modifying signalling events and thus be responsible for the observed cellular desensitization.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400092
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  • 2
    Electronic Resource
    Electronic Resource
    Biological effects of encapsulated insulin on transfected Chinese hamster ovary cells (1995)
    Springer
    Diabetologia 38 (1995), S. 180-186 
    Details
    ISSN: 1432-0428
    Keywords: Key words Insulin pharmacology ; insulin metabolism ; oral administration ; dose-response relationship ; cultured cells.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Oral administration of insulin incorporated into the wall of isobutylcyanoacrylate nanocapsule to diabetic rats induces a long-lasting normalization of their fasting glycaemia. In this study, we examined the biological action of encapsulated insulin on DNA and glycogen syntheses in Chinese hamster ovary cells transfected with the human insulin receptor gene. In the 10–11 mol/l – 10–9 mol/l concentration range, encapsulated insulin elicited responses comparable to those induced by native insulin: at 10–9 mol/l, the rates of glycogen and DNA synthesis were enhanced by factors 3 and 2.5, respectively. Encapsulated insulin at 10–7 mol/l evoked receptor desensitization although it did not induce receptor down-regulation and did not alter receptor recycling for up to 6 h. Chloroquine decreased the action of native insulin on glycogen synthesis, but did not affect the dose-response characteristics of encapsulated insulin. Acid-washing of the cells after 1 h of stimulation decreased maximal insulin responsiveness and provoked a dose response curve for encapsulated insulin similar to that of the native hormone. Direct measurement of effective insulin binding activity showed that encapsulated insulin (at 10–8 and 10–7 mol/l) was withdrawn from the incubation medium 5–8 times less efficiently than native insulin. These data are in agreement with previous results showing that the polymeric wall protects encapsulated insulin from degradation. Persistence of intact encapsulated insulin inside and outside the cell may result in modifying signalling events and thus be responsible for the observed cellular desensitization.[Diabetologia (1995) 38: 180–186]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400092
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  • 3
    Electronic Resource
    Electronic Resource
    Assessment of high-frequency neonatal ventilator performances (1997)
    Springer
    Intensive care medicine 23 (1997), S. 208-213 
    Details
    ISSN: 1432-1238
    Keywords: Key words High-frequency ventilation ; Pediatric intensive care
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To assess the efficacy and reliability of neonatal high-frequency ventilators. Design: Bench evaluation of neonatal high-frequency ventilators. Setting: Physiology department and university hospital neonatal intensive care unit. Interventions: HFV-Babylog 8000 (Dräger Medical), OHF 1 (Dufour), and SensorMedics 3100A (SensorMedics) ventilators were connected to a neonatal test-lung. Tidal volume, peak-to-peak pressure amplitude, and mean airway pressure were measured for several ventilator settings, endotracheal tube sizes, and lung compliances. Measurements and results: Increasing peak-to-peak pressure resulted in a linear increase in tidal volume delivery in the 0–30% range of maximum amplitude. No significant increase in tidal volume was observed with the HFV-Babylog8000 when pressure amplitude was above 50%. The maximum tidal volume delivered was substantially smaller with the HFV-Babylog8000 than with the OHF1 or SensorMedics3100A. Tidal volume increased with endotracheal tube size with all three ventilators. Increasing test-lung compliance resulted in lower tidal volumes only with OHF1. Decreasing mean airway pressure was responsible for a decrease in tidal volume delivery with HFV-Babylog8000. Conclusion: We found that under our test conditions two of the three ventilators delivered adequate tidal volumes at the usual frequency of 15Hz, regardless of the size of the endotracheal tube and of the mechanical properties of the respiratory system. When lung compliance increased or mean airway pressure decreased, both of which are common events during the recovery phase of hyaline membrane disease, we found that the intrinsic properties of two of the ventilators tested were responsible for a decrease in tidal volume. This decrease may account for some cases of heretofore unexplained hypercapnia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340050318
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  • 4
    Electronic Resource
    Electronic Resource
    Assessment of neonatal ventilator performances (1995)
    Springer
    Intensive care medicine 21 (1995), S. 753-758 
    Details
    ISSN: 1432-1238
    Keywords: Artificial ventilation ; Pediatric intensive care ; Positive end-expiratory pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To analyze efficiency and reliability of 4 modern neonatal ventilators under difficult test conditions. The ventilators tested were: Babylog 8000 (Dräger Medical), BP 2001 (Bear Medical Systems), Sechrist IV 100 B (Sechrist Industries), Infant Star (Infrasonics INC). Measurements and results Gas flow generation was tested by comparison of preset flow values with no resistance in the circuit to flow values obtained during interposition of a resistance in the inspiratory circuit. A decrease in gas flow was observed when interposition of a resistance in the inspiratory circuit increased peak inspiratory pressure to 60 cmH2O (gas flow decreased by 8% to 24% depending on the ventilator tested). The pressure limiting valve and the positive end-expiratory pressure valve were also evaluated in order to test their behaviour under different flow conditions. Flow-dependence of the pressure was noted for all ventilators except Babylog 8000. Assessment of the reliability of pressure monitoring revealed either ‘under’ or ‘over’ estimation of peak inspiratory pressure and positive end-expiratory pressure depending on the ventilator tested. Conclusion For the best clinical use of mechanical ventilators, neonatologists should be aware of these limitations. Therefore a regular assessment of ventilator performance and monitoring reliability is recommended.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01704743
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  • 5
    Electronic Resource
    Electronic Resource
    Clinical outcome and long-term management of 17 patients with propionic acidaemia (1996)
    Springer
    European journal of pediatrics 155 (1996), S. 205-210 
    Details
    ISSN: 1432-1076
    Keywords: Propionic acidaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A retrospective study was performed on the clinical outcome and long-term treatment of 17 patients with propionic acidaemia diagnosed during the last 20 years in our hospital. The study group consisted of 12 patients with early onset type of disease and 5 patients with late onset. Seven (41%) patients died, five with early onset and two with late onset. The deceased early onset patients had a median survival of 0.4 years while the deceased late onset patients died at the age of 2.8 and 4 years respectively. Median age of the living early onset patients was 5.2 (1–9.25) years, the late onset patients were 4,7 and 23 years old. Patients were all treated with natural protein restriction and in most cases carnitine and metronidazole were added. The early onset patients were almost all treated with daily home tube feeding. The mean natural protein intake of early onset patients (6.3±1.5 g/day) was significantly lower than the natural protein intake of late onset patients (17.6±5.3 g/day). Supplemental protein intake was higher in early onset patients. The general neurological outcome of our study group was satisfactory with a better outcome for early onset patients. As to growth, many patients showed a failure to thrive, this was particularly for height. The strong protein restriction during the first years of life probably contributed to this. Conclusion The prognosis for patients with propionic acidaemia appeared to be satisfactory in terms of survival and outcome characteristics such as neurological and mental development. Despite these results the authors feel that the prognosis and quality of life of these patients might be improved with liver transplantation or possibly somatic gene therapy in the future.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01953939
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  • 6
    Electronic Resource
    Electronic Resource
    Characteristics and biological behaviour of 99mTc-labelled hydroxyacetyltriglycine, a potential alternative to 99mTc-MAG3 (1997)
    Springer
    European journal of nuclear medicine 24 (1997), S. 1374-1379 
    Details
    ISSN: 1619-7089
    Keywords: Key words: Hydroxyacetyltriglycine ; Mercaptoacetyltriglycine ; Labelling characteristics ; Biological behaviour ; Biodistribution studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Substitution of the oxidation-sensitive thiol function of mercaptoacetyltriglycine (MAG3) by a hydroxyl group yields a tetraligand (hydroxyacetyltriglycine or HAG3) which is almost insensitive to oxidation and has the advantage over MAG3 that it can be stored safely without protection of the alcohol function. We found that deprotected HAG3 could be directly labelled at alkaline pH (pH≥11.5) and room temperature in high yield (〉95%). Results of electrophoresis experiments suggested a comparable structure for 99mTc-HAG3 and 99mTc-MAG3, namely binding of an oxotechnetium(V)core via three deprotonated amides and a deprotonated hydroxyl group. Biodistribution studies in mice at 10 min and 30 min p.i. showed a slightly higher urinary excretion, a faster renal transit and a significantly lower hepatobiliary handling for 99mTc-HAG3 than for 99mTc-MAG3. In a baboon, the 1-h plasma clearance of 99mTc-HAG3 was clearly higher than that of 99mTc-MAG3. Its plasma protein binding was in the same order as that of Hippuran and much lower than that of 99mTc-MAG3. Evaluation in a human volunteer confirmed the favourable biological characteristics of 99mTc-HAG3, namely a rapid renal excretion, a high 1-h plasma clearance and a negligible hepatobiliary handling. The results indicate that 99mTc-HAG3 may be an easy-to-prepare and practical substitute for 99mTc-MAG3 with improved renal excretion characteristics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590050163
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  • 7
    Electronic Resource
    Electronic Resource
    Complexes of technetium-99m with tetrapeptides containing one alanyl and three glycyl moieties (1996)
    Springer
    European journal of nuclear medicine 23 (1996), S. 40-48 
    Details
    ISSN: 1619-7089
    Keywords: Technetium-99m tetrapeptides ; Renal tracer agent ; Technetium-99m mercaptoacetyltriglycine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently, we have shown that tetrapeptides can be efficiently labelled with technetium-99m by direct labelling at alkaline pH. Tetrapeptides can be considered derivatives of mercaptoacetyltriglycine (MAG3) in which the mercaptoacetyl moiety is replaced by an amino acid residue. In view of the interesting biological properties of some C-methyl substituted derivatives of99mTc-MAG3, we have now synthesised and evaluated the complexes of99mTc with tetrapeptides containing three glycyl (G) moieties and oned- orl-alanyl (A) moiety. In mice,99mTc-l-GAGG,99mTc-d-GGAG and99mTc-l-GGAG showed a rapid and high renal excretion, comparable to that of99mTc-MAG3. Renal handling was somewhat reduced for isomersd andl of99mTc-AGGG and99mTc-d-GAGG and markedly inferior for99mTc-l-GGGA and99mTc-d-GGGA. In the baboon,99mTc-l-AGGG,99mTc-d-AGGG and99mTc-l-GAGG showed a comparable or even higher 1-h plasma clearance than99mTc-MAG3.99mTc-d-GAGG,99mTc-l-GGAG and99mTc-d-GGAG were characterised by a lower plasma clearance and the clearance of99mTc-l-GGGA and99mTc-d-GGGA was remarkably low. The three99mTc-labelled tetrapeptides with the highest plasma clearance in a baboon were compared with99mTc-MAG3 in a human volunteer.99mTc-l-AGGG and99mTc-l-GAGG had a roughly similar plasma clearance as99mTc-MAG3. The clearance of99mTc-d-AGGG was significantly lower and liver uptake was clearly visible with this compound. Left kidney renograms of99mTc-l-AGGG and99mTc-d-AGGG indicated moderate kidney accumulation. On the other hand, the renogram obtained after injection of99mTc-l-GAGG had an excellent shape and the maximum kidney concentration was slightly higher than for99mTc-MAG3. These results show the importance of the position of the methyl substituent on the99mTc-tetrapeptide with respect to its biological behaviour.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01736988
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  • 8
    Electronic Resource
    Electronic Resource
    Reduction of contamination risks during clinical studies with Technegas (1999)
    Springer
    European journal of nuclear medicine 26 (1999), S. 1349-1352 
    Details
    ISSN: 1619-7089
    Keywords: Key words: Technegas ; Contamination ; Lung ventilation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. During patient studies with the Technegas equipment in our department, we regularly detected small to considerable contaminations of the operator and in the area surrounding the apparatus. These contaminations were found to be of different origin: residual activity in the tubing from the apparatus to the patient which diffuses after deconnection, residual activity and small particles of the destroyed carbon crucible in the apparatus which are dispersed during opening of the door of the gas preparation chamber, leakage at the patient site during studies in uncooperative patients and a dysfunctioning valve inside the apparatus. To reduce the contamination risks, we made some adaptations to the apparatus. In the first place, the dysfunctioning valve was replaced. In addition, a powerful air exhaust pump with an efficient filter was installed. It was connected with (1) a newly installed transparent box in front of the door of the gas preparation chamber, (2) a dome on a flexible arm which can be positioned above the patient’s face during the examination and (3) a nipple on which the mouthpiece can be placed after the study. After these adaptations, a study showed the absence of measurable contamination on the clothing of the personnel handling the apparatus. Occasionally, considerable contamination was still measured on the gloves worn during filling of the carbon boat with generator eluate, but only small contaminations (up to 9.25 kBq) were measured on the mouthmask worn by the operator during administration of the Technegas. This results in a maximum effective dose equivalent fromactivity deposited in the lungs of 0.008 µSv per study. The total body dose of the operator from external radiation for one Technegas examination was determined to be 2 µSv. The highest dose rate was measured during filling of the crucible (0.2 mSv/h).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590050594
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  • 9
    Electronic Resource
    Electronic Resource
    Anchoring transitions with polar and non-polar nematic liquid crystals on incompletely oxidized silane substrates (1999)
    Springer
    The European physical journal 8 (1999), S. 245-249 
    Details
    ISSN: 1434-6036
    Keywords: PACS. 61.30.Gd Orientational order of liquid crystals; electric and magnetic field effects on order - 64.70.Md Transitions in liquid crystals - 68.45.-v Solid fluid interfaces
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: The active oxygen gas arising from a plasma reactor is used to realize progressive chemical modifications onto silane coatings that could be particularly interesting as alignment layers for liquid crystal display applications. Depending on the oxygen density grafted onto the substrate, these alignment layers provide different zenithal anchoring angles, or pretilt angles, with anchoring transitions, for polar and non-polar nematic liquid crystals as 5CB and MBBA, respectively. The anchoring transitions are found to be smoother with the polar nematics. Such a behavior is discussed in terms of the differential wetting model by adding a cosine term to the interaction energy between the nematic and the substrate. A local justification is proposed for this symmetry breaking term.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s100510050687
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  • 10
    Electronic Resource
    Electronic Resource
    Continuous venovenous haemodiafiltration in the acute phase of neonatal maple syrup urine disease (1997)
    Springer
    Journal of inherited metabolic disease 20 (1997), S. 463-472 
    Details
    ISSN: 1573-2665
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Maple syrup urine disease results in accumulation of leucine and its metabolites, which may lead in the long term to neurological dysfunction. In acute neonatal crises, large amounts of leucine may be removed by continuous venovenous haemofiltration. This extracorporeal technique has its risks and hazards, which increase with duration of treatment. We report three neonates in life-threatening conditions due to maple syrup urine disease, treated for not more than 12h with various continuous venovenous techniques: continuous haemofiltration, haemodiafiltration and haemodialysis. The efficiency of and tolerance to these techniques was evaluated. For all three patients, plasma leucine levels decreased dramatically from 2186, 3818 and 2536 µmol/L to 1131, 1275 and 488 µmol/L, respectively. Leucine clearance obtained was 4.28 ml/min in haemodiafiltration. Their patients' neurological status improved rapidly and they have a normal developmental quotient at 22 months, 13 months, and 11 months of age, respectively. Tolerance was good except for hypothermia and drop in haematocrit in all cases. Haemodiafiltration management was more cumbersome and time consuming because it required continual adjustment of the substitution fluid flow rate to precisely balance inflow and outflow rates. We recommend continuous venovenous haemodialysis as the therapy of choice. It might be anticipated that improvement of this technique, by increasing dialysate flow rate and blood flow rate, will allow leucine concentration to be decreased below 1000 µmol/L within 6-8 h, whatever the initial level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1005314025760
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