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Biomedical subjects

I Kuhn

Publications and source records attributed to I Kuhn.

At least 37 records · Page 2Linked to original sources

[Heat production from reaction of inhalation anesthetics with dry soda lime].

UNLABELLED: There are some case reports about excessive heat production in the absorbent canister when sevoflurane or enflurane are washed into a circle containing dried soda lime. This observation was often made in the DRAGER ISO 8 circle system with the gas inlet upstream of the soda lime canister with the gas-flow from bottom to top. METHODS: The temperature in the center of an absorbent canister was measured 3.0 cm and 7.5 cm above the bottom. Soda lime (DRAGERSORB 800) was dried in an O2 stream for 2-3 days until there was no further loss in weight. 5 Vol% of desflurane, enflurane, isoflurane and sevoflurane in 2 1/min O2 or 4 Vol% of halothane in 2.5 I/min O2 were continuously fed into the canister. The concentration of the respective inhalational agents were measured after the soda lime canister using a DATEX Capnomac. Experiments were performed at ambient temperatures of 20-22 degrees C. RESULTS: A considerable temperature increase was achieved with all anaesthetics. The highest temperatures were measured at the upper sensor with 56-58 degrees C for desflurane, 76-80 degrees C for enflurane and isoflurane, 84-88 degrees C for halothane and 126-130 degrees C for sevoflurane. IR-detection for some agents was considerably delayed or the time course indicated that other compounds might have formed which absorb at the wavelength monitored. DISCUSSION: The high temperatures indicate the degradation rather than absorption of the volatile anaesthetics. CO is known to be degradation product of all currently used volatile anaesthetics except sevoflurane. Sevoflurane, however, produced the highest temperatures passing through dried soda lime. There are no reports about new specific breakdown products for sevoflurane on dried soda lime.

Anesthetics, Inhalation↗

[Effect of halothane, enflurane and isoflurane on the pharmacodynamics of mivacurium in children].

INTRODUCTION AND OBJECTIVE: Mivacurium is a new non-depolarising muscle relaxant with a relatively rapid onset and short duration of action. In children, intravenous injection of 0.2 mg/kg produces satisfactory relaxation. Because inhalational anaesthetics have been found to enhance the potency of muscle relaxants we determined if onset or recovery times following mivacurium are influenced by inhalation of halothane (HAL), enflurane (ENF) or isoflurane (ISO). METHODS: After intramuscular induction, 36 surgical children (2-6 years, ASA I) were randomly assigned to inhale either HAL (n = 12); ENF (n = 12) or ISO (n = 12). The train-of four (TOF) response was determined electromyographically (Relaxograph, Datex) at 20-second time intervals. Following ten minutes of inhalation of either HAL, ENF or ISO (0,8; 1,2; 1,0 vol% respectively) in N2 O/O2 (2:1), 0.2 mg/kg of mivacurium was injected intravenously. Patients were intubated at maximal T1-suppression and the intubating conditions were judged according to a graded score. Upon recovery of T1 = 25%, six patients in each group were antagonised with 30 micrograms/kg of neostigmine and 15 micrograms/kg of atropine; the recovery indices were compared with those from non-antagonised patients. Differences between groups were tested with multifactorial analysis of variance (p < 0.05). RESULTS: Intubating conditions were graded as "excellent" or "good" in all patients but one who showed moderate breath holding following the tube passage. Onset times of mivacurium were not different between patients receiving HAL: 2.4 min +/- 0.52 (+/ SD); ENF: 2.4 min +/- 0.55 or ISO: 2.6 min +/- 0.68. Time to T1 = 25% was 7.6 min +/- 2.91 (HAL); 7.9 min +/- 1.55 (ENF) and 8.6 min +/- 2.30 (ISO). Recovery indices were not significantly different between groups. Total duration of action in non-antagonised patients was 13.0 min +/- 3.32 (HAL); 14.3 min +/- 4.01 (ENF) and 19.6 min +/- 5.17 (ISO), whereas antagonised duration of action was 13.4 min +/- 5.11 (HAL); 13.3 min +/- 1.97 (ENF) and 15.6 min +/- 4.25 (ISO). The shorter total duration of action in patients receiving neostigmine (average 0.5-2 minutes) was statistically insignificant. DISCUSSION AND CONCLUSION: Following injection of 0.2 mg/kg of mivacurium, no clinically relevant differences in onset or recovery times were found between children receiving halothane, enflurane or isoflurane. No differences in heart rate or blood pressure were found between groups. Compared to previous investigations with mivacurium, we noted a 30-60% longer mean onset time and a 30% shorter mean spontaneous recovery time. This may be explained by the lower mean age of our patients, which correlates with a relatively higher volume of distribution, resulting in lower plasma concentrations if the dose is calculated per kilogramme body weight. The reduction of the mean recovery time by 2 minutes following neostigmine injection seems to be clinically irrelevant. Similar to adult, a twofold ED95 produces satisfactory surgical muscle relaxation in children receiving mivacurium. Thus, its onset time is comparable to that of vecuronium or atracurium. The shorter duration of action offering a tighter control over relaxation may be of clinical advantage in this age group.

Adult↗

Recombinant vaccine development: a novel approach to ectoparasite control. A review of development of a recombinant vaccine for hypodermosis based on hypodermin A.

Cattle grubs (Hypoderma lineatum and H. bovis) are obligate parasites of cattle for most of their one year life cycle. Previously exposed animals become resistant to productive reinfestation, presumably as a result of immune system involvement, suggesting potential control by vaccination. Research progress towards development and utilization of a recombinant subunit vaccine for hypodermosis is described.

Animals↗

Structure-function studies of the epidermal growth factor domains of human thrombomodulin.

Structure-function relationships in the 6 epidermal growth factor-like domains of human thrombomodulin (TME, residues 227-462) were studied by deletion mutagenesis. Purified and characterised proteins were used for kinetic studies. Deletion of EGF1, EGF2 and residues 310-332 in EGF3 had no effect on thrombin binding (Kd) or on kcat/KM for protein C activation by the thrombin-thrombomodulin complex. Deletion of the rest of EGF3 and the interdomain loop between EGF3 and EGF4 had no effect on Kd but decreased kcat/KM to 10% of TME. Deletion of residues 447-462 of EGF6 had no effect on kcat/KM but increased Kd for thrombin approximately 6-fold. Thus, the region 333-350 in EGF3-4 is critical for protein C activation by the thrombin-thrombomodulin complex and the region 447-462 in EGF6 is critical for thrombin binding.

Base Sequence↗

Oxidation of a specific methionine in thrombomodulin by activated neutrophil products blocks cofactor activity. A potential rapid mechanism for modulation of coagulation.

Endothelial thrombomodulin (TM) plays a critical role in hemostasis as a cofactor for thrombin-dependent formation of activated protein C, a potent anticoagulant. Chloramine T, H2O2, or hypochlorous acid generated from H2O2 by myeloperoxidase rapidly destroy 75-90% of TM cofactor activity. Activated PMN, the primary in vivo source of biological oxidants, also rapidly inactivate TM. Oxidation of TM by PMN is inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase. Both Met291 and Met388 in the six epidermal growth factor-like repeat domain are oxidized; however, only substitutions of Met388 lead to TM analogues that resist oxidative inactivation. We suggest that in inflamed tissues activated PMN may inactivate TM and demonstrate further evidence of the interaction between the inflammatory process and induction of thrombotic potential.

Adult↗

Renal elimination of magnesium as a parameter of bioavailability of oral magnesium therapy.

Magnesium is an important cation in human physiology, especially in the regulation of membrane proteins, as a cofactor for various enzyme systems and in neuromuscular transmission. Magnesium deficiency leads to severe impairment in muscle function, particularly in cardiovascular diseases. Classical bioavailability studies with magnesium cannot be carried out for several reasons. As the magnesium concentration in plasma is extraordinarily well regulated, renal elimination proves to be the best method to determine the absorption of orally administered magnesium. Magnesium pools must first be filled, and the saturation phase of renal elimination then equals the degree of absorption. This parameter of bioavailability shows the percentage of eliminated magnesium in comparison to the administered dose. Eighteen healthy male volunteers were included in this study to compare 5 mg magnesium-DL-hydrogen aspartate with magnesium-L-hydrogen aspartate. After a saturation phase, the test substances were administered in random order. Blood samples for determination of magnesium concentrations were taken, but no typical pharmacokinetic concentration curves were obtained. The areas under the concentration-time curves were equal for both formulations (x = 40.22 [mval*h/l]). The bioavailability of both substances was determined from the renal elimination. No significant difference was found between both treatments. Bioavailability of 5 mg magnesium-DL-hydrogen aspartate was 44.5% and for magnesium-L-hydrogen aspartate 41.7%. It is evident that this method of magnesium determination is practical, comfortable for volunteers and gives reliable results in comparing the absorption of magnesium formulations.

Administration, Oral↗

Gastric potential difference measurement as a quantification of gastrointestinal tolerability comparing a buffered acetylsalicylic acid formulation versus plain acetylsalicylic acid.

Two different acetylsalicylic acid (ASA, CAS 50-78-2) formulations (Aspirin) were compared regarding their gastric mucosal tolerability. After administration of plain ASA, buffered ASA and ASA placebo the decrease of gastric potential difference (GPD) was measured. Evaluation of the GPD parameters showed a better tolerability of buffered ASA than of plain ASA. It was therefore concluded that buffered ASA effects less gastric mucosal irritation than plain ASA.

Adult↗

Dialysability of dimethindene maleate (Fenistil) from blood after intravenous injection.

Dimethindene, an antihistaminic drug, is the treatment of choice in dialysis patients suffering from skin itching. During hemodialysis procedures not only toxic metabolites, but also drugs are extracted from plasma. To answer the question if dimethindene is dialyzable from plasma, three healthy male volunteers received 4 mg of dimethindene solution intravenously. Ten minutes later 100 ml cubital vein blood was taken and 25,000 I.E. Liquemine was added. Plasma was separated and pumped through a cuprophan hollow fiber dialyzing module with an effective surface of 35 cm2. In periods of ten minutes samples of plasma and dialysate were taken to analyze their dimetindene concentrations. A mean clearance of 38 ml/min*m2, SD 10.2 and coefficient of variation [%] 26.8 was found. This is comparable to the well known clearance of theophylline, so it can be considered that dimethindene is eliminated from plasma during hemodialysis procedures.

Algorithms↗

Iontophoresis--is there a future for clinical application?

Transdermal application of drugs is a field of great importance in medical therapy. The application is painless and may be controlled at any time. Iontophoresis is one method for transdermal application of substances, especially for larger or charged molecules which cannot be administered by a simple transdermal route. The problems arise from the complex equipment and the electrical properties of the skin. A better understanding of skin structure and electric transmission through human skin has led to renewed interest in iontophoresis as an administration mode. Iontophoresis is the method of choice in administration of certain local anesthetics and has had its greatest success in therapy of hyperhidrosis. New applications are to be expected, particularly in administration of peptide and protein drugs.

Administration, Cutaneous↗

Vaccination against polyoma virus (PyV) tumors using vaccinia-PyV recombinants: a major tumor-specific transplantation antigen (TSTA) epitope resides within the C-terminal segment of middle-T protein.

We previously reported that inoculation of rats with live vaccinia virus (VV) recombinants VVpyMT, VVpyLT expressing either the middle-T (MT) or large-T (LT) proteins of polyomavirus (PyV) can elicit immunity to challenge with syngeneic PyV-tumor cells. We now report the results of cross-vaccination studies. VVpyMT was ineffective against cells expressing LT protein but prevented development of MT-expressing cells. Conversely, the VVpyLT was ineffective against MT-expressing cells. In the two experiments performed, tumor growth enhancement rather than retardation was observed in VVpyLT-vaccinated animals receiving PyV-LT (FRLTI) challenge tumor cells. To determine the location of the major TSTA within MT, a further VV recombinant (VVpyMT/Cfr) was constructed that expresses only the unique C-terminal segment of MT. VVpyMT-Cfr and VVpyMT were equally effective in eliciting tumor immunity, indicating the presence of a major TSTA epitope within the unique C-terminal region of MT.

Amino Acid Sequence↗

Characterization of a surface antigen of Eimeria tenella sporozoites and synthesis from a cloned cDNA in Escherichia coli.

An antigenic surface protein of Eimeria tenella sporozoites has been identified that is the target of two neutralizing monoclonal antibodies Ptn 7.2A4/4 and Ptn 9.9D12. The antigen as isolated from the parasite is composed of a 17 kDa polypeptide and a 8 kDa polypeptide linked by a disulfide bridge. De novo synthesis of the antigen does not begin until approximately 16-20 h after the initiation of oocyst sporulation. A cDNA library was constructed using mRNA from sporulated oocysts and a clone encoding the antigen was isolated. The Ta4 gene encodes a single polypeptide of 25 kDa which contains the 17 and 8 kDa polypeptides. The protein has been synthesized in Escherichia coli either directly or as part of a beta-galactosidase fusion protein. The products synthesized in E. coli are single polypeptides and are not cleaved to two polypeptides as is seen in the parasite. The products accumulate in bacteria in an insoluble form which can be solubilized and renatured to an immunoreactive form.

Amino Acid Sequence↗