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Biomedical subjects

U Grundmann

Publications and source records attributed to U Grundmann.

At least 55 records · Page 3Linked to original sources

[Comparative effectiveness and tolerance study of a new galenic etomidate formula].

OBJECTIVE AND STUDY DESIGN: One of the major disadvantages of etomidate is the high frequency of pain on injection. A new galenic formulation based on a lipid emulsion for etomidate (Etomidat-Lipuro) was compared with the commercial standard (etomidate in propylene glycol, Hypnomidate) in a prospective, randomised, double-blind clinical evaluation in 232 patients undergoing elective surgery in general anaesthesia. The patients were premedicated with flunitrazepam 2 hours before the investigation. Two intravenous cannulas were inserted in veins of forearm or back of the hand. One cannula was only used for the application of etomidate and removed immediately after injection. General anaesthesia was induced with 0.3 mg/kg etomidate at an injection rate of 20 mg/30 s. If the patient did not complain of pain or other sensations during injection spontaneously, he was questioned for 15 s after beginning of injection. The arm used for application of etomidate was kept free of any manipulation during the operation and the following five postoperative days. RESULTS: There were marked differences between the two etomidate preparations concerning venous irritation. About 20% of the patients receiving the hypnotic in propylene glycol complained spontaneously of pain on injection, whereas none with the lipid emulsion. No difference was found in the incidence of myoclonic movements. The time interval between the beginning of injection and loss of eyelid closure reflex was about 50 s and not different for the two galenic formulations. Blood pressure during and after induction of anaesthesia did not differ. The heart rate in the group of patients with etomidate in lipid emulsion was slightly increased before and immediately after intubation compared to the propylene glycol group. 4% of the patients in the propylene glycol group suffered from postoperative venous complications as reddening, swelling, induration or pain. These complications could not be seen in the lipid emulsion group.

Adult↗

[Effect of the volatile anesthetics halothane, enflurane and isoflurane on liver circulation in the human].

In 40 patients with normal liver function total hepatic blood flow (HBF) was determined by the indocyanine-green clearance method simultaneously with haemodynamic parameters, including cardiac output by means of the noninvasive thoracic electrical bioimpedance method. Furthermore, the influence of halothane, enflurane or isoflurane on HBF and the interaction with haemodynamic parameters was studied. HBF and the cardiocirculatory parameters were determined under normal conditions (waking state) and the 40 patients were then divided into 4 groups (each n = 10). After standardised induction of anaesthesia (0.3 mg/kg etomidate and 2 micrograms/kg fentanyl) and tracheal intubation (1.5 mg/kg suxamethonium chloride) an inhalation anaesthesia in O2/air under control of normal end tidal carbon dioxide concentration was performed by intermittent positive pressure ventilation. Anaesthesia was maintained in the 4 groups either with 1 MAC halothane, 1 MAC enflurane, 1 MAC isoflurane or 1.3 MAC isoflurane. The measurements were repeated at a steady of the desired end expiratory concentration of the respective volatile anaesthetic. All three anaesthetics produced a significant and comparable decrease of cardiac output and arterial blood pressure. Differences between halothane, enflurane and isoflurane in respect of haemodynamic parameters were only minimal. Contrariwise, marked differences could be seen in the effects of the anaesthetics on HBF. In the presence of halothane and enflurane HBF dropped to 58% and 56% resp. of the control value, whereas during isoflurane anaesthesia HBF remained unchanged. Furthermore, only during halothane anaesthesia a significant correlation between arterial blood pressure and HBF could be observed indicating a loss of autoregulation of the hepatic blood flow.

Adolescent↗

Immunochemically detected placental proteins and their biological functions.

During the last 20 years a systematic search for proteins occurring in human term placenta (afterbirth) has been performed in our laboratory. As a result more than 30 soluble placental proteins and at least 20 different solubilized antigens apparently derived from the placental membranes have been identified by immunochemical methods in extracts from human term placentas. Most of these proteins have already been isolated to purity and characterized by their physicochemical parameters. Specific antisera to these proteins were obtained by immunizing animals with the corresponding purified proteins. They were used detect and localize these antigens by immunochemical methods in the placenta and in other human tissues. Sensitive immunochemical assays have been developed to exactly quantitate the new proteins in body fluids and to find out the diagnostic significance of measurement of these proteins in pregnant women and in patients with tumors and other diseases. Another aim was to elucidate the biological functions of our immunochemically detected proteins. The results obtained thus far are reported.

Female↗

[Comparative studies of atracurium and vecuronium for medium-length surgical procedures in infants and young children].

Onset time, intubation condition and recovery time after single bolus injection of atracurium (0.3 mg/kg in body weight less than 10 kg (Group 1), 0.5 mg/kg in body weight greater than 10 kg (Group 2] and vecuronium (0.05 mg/kg in body weight less than 10 kg (Group 3), 0.1 mg/kg in body weight greater than 10 kg (Group 4] were studied in 40 infants and children anaesthetised with halothane. At the end of the onset time (time from the end of the bolus injection of the muscle relaxant until the maximal twitch depression of the m. adductor pollicis) the intubation conditions were judged as good or very good in both groups. The onset time after bolus injection of atracurium (92.5 +/- 31.9 sec in Group 1, 117.0 +/- 25.2 sec in Group 2) was slightly shorter than after vecuronium (135.7 +/- 64.1 sec in Group 3, 123.3 +/- 26.8 sec in Group 4). The duration from the time of injection to 75% recovery of T1 had been longer by using atracurium (45.2 min in Group 1 + 2) than by vecuronium (36.6 min in Group 3, 34.2 min in Group 4). In infants (Group 1 + 3) the recovery time (duration from 25% to 75% recovery of control twitch height) after relaxation with atracurium as well as vecuronium was longer than in children (Group 2 + 4). Neither cardiovascular side effects nor signs of histamine release occurred after the injection of both muscle relaxants at our dosage level. It is concluded that in infants and children atracurium is a real alternative to vecuronium for relaxation for medium long surgical procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

Cardiac output and liver blood flow in humans: effect of the volatile anesthetic halothane.

In 40 men with normal circulatory and liver function, from whom 10 were undergoing general anesthesia with halothane for minor orthopedic surgery, the relationship between hemodynamic parameters and total hepatic blood flow (HBF) was investigated. Cardiac output (CO) was measured noninvasively by means of the thoracic electrical bioimpedance method, systemic arterial blood pressure (BPsys, BPdia, mean arterial pressure) by an automated oscillometric device and HBF by indocyanine green clearance. In the subjects without halothane anesthesia no relationship was found between BP and HBF, but a significant correlation could be seen between CO and HBF, whereby the fraction of HBF decreased with increasing CO. In contrast, in the presence of halothane the systemic arterial blood pressure correlated with the HBF, indicating a loss of autoregulation of the liver circulation.

Adult↗

Cloning and prokaryotic expression of a biologically active human placental aldose reductase.

cDNA clones coding for human aldose reductase (AR) were isolated by antibody screening of a placental lambda gt11 cDNA library. The cDNA comprises the entire coding region and has a total length of 1,394 bp. The sequence deduced from the open reading frame encodes a protein of 316 amino acids and its amino acid composition is identical to the placental protein 9 (PP9), whose isolation and characterization were described by Bohn et al. (1982). The amino acid sequence of the placental human AR shows high homology to the rat AR; both proteins belong to the same protein superfamily as human liver AR, frog lens rho-crystallin, and bovine lung prostaglandin F synthase. Northern blot hybridization analysis revealed a size for the AR mRNA of approximately 1,500 bases. In addition to the full-length cDNA, one lambda gt11 clone was isolated which carries a putative intron of 597 bp at nucleotide position 754, corresponding to amino acid position 247. Expression of the AR cDNA in Escherichia coli resulted in the synthesis of a protein with a molecular weight of approximately 35 kD which can be immunoprecipitated specifically with antiserum raised against PP9. Despite the absence of a typical signal sequence, the human aldose reductase is partially translocated into the periplasm of the E. coli cells, where it is present in an enzymatically active form.

Aldehyde Reductase↗

Cloning and expression of a cDNA encoding human placental protein 11, a putative serine protease with diagnostic significance as a tumor marker.

The placental protein 11 (PP11) can act as a tumor marker because of its specific association with various forms of cancer. A lambda gt11 cDNA library prepared from human placenta was screened with a polyclonal anti-PP11 antiserum. Out of 10(6) independent clones, only one clone reacted with the anti-PP11 antiserum. The isolated cDNA coded only for the carboxy-terminal part of PP11 and was subsequently used to rescreen a lambda gt10 placental cDNA library. Two cDNA clones out of 10(6) screened were identified encoding the entire protein of 369 amino acids, including a typical hydrophobic signal sequence of 18 amino acids. Expression of the PP11 cDNA coding sequence in Escherichia coli resulted in the synthesis of a protein with the expected size which can be specifically immunoprecipitated with anti-PP11 antiserum. Fractionation experiments revealed that two forms of the protein are present in the bacterial cell: a higher-molecular-weight form of approximately 42 kD in the cytoplasm and a smaller-molecular-weight form of approximately 42 kD in the periplasm. This result indicates that PP11 can be synthesized in E. coli and is process by removal of the hydrophobic signal sequence. Both the placental and the processed recombinant PP11 protein exhibit a protease activity.

Amino Acid Sequence↗

Characterization of cDNA encoding human placental anticoagulant protein (PP4): homology with the lipocortin family.

A cDNA library prepared from human placenta was screened for sequences encoding the placental protein 4 (PP4). PP4 is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade. Partial amino acid sequence information from PP4-derived cyanogen bromide fragments was used to design three oligonucleotide probes for screening the library. From 10(6)independent recombinants, 18 clones were identified that hybridized to all three probes. These 18 recombinants contained cDNA inserts encoding a protein of 320 amino acid residues. In addition to the PP4 cDNA we identified 9 other recombinants encoding a protein with considerable similarity (74%) TO PP4, which was termed PP4-X. PP4 and PP4-X belong to the lipocortin family, as judged by their homology to lipocortin I and calpactin I.

Amino Acid Sequence↗

Synthesis of human factor XIIIa in bacterial cells.

The coding sequence for human factor XIIIa (FXIIIa) was introduced into Escherichia coli expression vectors. Bacterial cells transformed with the recombinant plasmids synthesized fusion proteins of the expected molecular weights and the proteins were shown to be immunoreactive with anti-FXIII antibodies. Furthermore, with the help of oligodeoxynucleotide synthesis, we constructed a plasmid which directs the synthesis of the human FXIIIa protein in the unfused form. Sequence determination at the aminoterminus of this protein revealed the identical sequence compared to placental FXIIIa. The protein is expressed intracellularly in a denatured and biologically inactive form. It constitutes approximately 2% of total cellular protein and can easily be purified by standard methods.

Amino Acid Sequence↗

Isolation and expression of cDNA coding for a new member of the phospholipase A2 inhibitor family.

The placental protein PP41,2 was shown to have thromboplastin-inhibitor activity. We used partial amino acid sequence information from PP4 cyanogen bromide fragments to design oligonucleotide probes for the screening of a human placental cDNA library. In addition to the PP4 cDNA we isolated a cDNA coding for a protein with considerable homology which we subsequently termed PP4-X. PP4 and PP4-X belong to the phospholipase A2 inhibitor family, as judged by their homology to lipocortin I and calpactin I3. The full-length PP4-X cDNA encodes a protein of 321 amino acid residues including a fourfold repeat structure. Northern blot analysis using the PP4-X cDNA reveals two hybridizing RNA species of approximately 1400 nucleotides and 2500 nucleotides, respectively. The shorter one could well represent the PP4-X transcript which is in good agreement with the isolated cDNA insert of 1326 nucleotides. Expression of the PP4-X coding sequence in E. coli resulted in the appearance of a protein which crossreacts with antibodies raised against PP4.

Annexin A5↗

Characterization of cDNA coding for human factor XIIIa.

A cDNA library prepared from human placenta has been screened for sequences coding for factor XIIIa, the enzymatically active subunit of the factor XIII complex that stabilizes blood clots through crosslinking of fibrin molecules. Two oligonucleotides, based on the amino acid sequences of tryptic peptides of factor XIIIa, were used as hybridization probes. Of 0.36 X 10(6) independent recombinants, 1 clone was identified that hybridized to both probes. The insert of 1704 base pairs coded for the amino-terminal 541 amino acid residues of the mature factor XIIIa molecule. Blot-hybridization analysis using this cDNA as a probe showed that the factor XIIIa mRNA from placenta has a size of approximately 4000 bases. The insert was used to rescreen cDNA libraries and to identify further factor XIIIa-specific sequences. The total length of the isolated factor XIIIa cDNA is 3905 bases, and it codes for a protein of 732 amino acids. In spite of the presence of factor XIII in blood plasma, we could not identify a leader sequence typical for secreted proteins.

Amino Acid Sequence↗

Embryonic induction and cation concentrations in amphibian embryos.

Explanted ectoderm from early gastrulae of Triturus alpestris was treated with the Na-K ionophore gramicidin (10(-9) to 10(-5) M) and the Ca-ionophore A 23187 (10(-7) to 10(-5) M). The ectoderm developed almost exclusively to atypical epidermis as in the control explants. When the ectoderm was treated with ouabain (10(-4) M), intracellular Na+ increased about 4.4-fold and K+ was reduced by half. Mesenchyme cells in small number differentiated in about 40% of the ouabain-treated explants. The time course of total Na+ and K+ ion concentrations was measured over a period of 72 h in ectoderm of T. alpestris after induction with vegetalizing factor and in control explants. In the first 15 h after explantation, no significant differences between control and induced explants were found. Thereafter, the steady state concentration of K+ decreased in the induced explants, whereas the steady-state concentration of Na+ slightly increased. The membrane resting potential recorded intracellularly of ectoderm sandwiches from early gastrula stages was found to be -41.3 mV in control and -59.3 mV in induced explants. From the specific conductances and permeabilities of non-induced and induced cells it is concluded that the induction process leads to a differentiation of the cell membrane, which acquires the characteristics of ionic selectivity. Ectoderm from Ambystoma mexicanum forms neural or neuroid tissue, mesenchyme and melanophores after explantation in salt solution in up to 50% of the explants without any additions. Isolated Ambystoma ectoderm is therefore not suitable for test experiments.

Ambystoma↗

Molecular cloning and sequencing of mRNAs coding for minor adult globin polypeptides of Xenopus laevis.

Globin mRNA was isolated from immature red blood cells of an adult Xenopus laevis female. mRNA/cDNA hybrids were integrated in the Pst I cleavage site of pBR 322 by G/C tailing, and cloned in Escherichia coli strain HB 101. By restriction site analysis as well as hybridization behaviour we identified two clones coding for minor adult alpha and beta globin chains. Nucleotide sequence analysis and derived amino acid sequences are presented.

Amino Acid Sequence↗

Restriction patterns of adult chicken globin genes at early and late stages of embryonic development.

Globin mRNA isolated from anemic chicken was transcribed into cDNA and integrated into the Pst I cleavage site of plasmid pBR 322. After cloning in E. coli strain HB 101 and colony hybridization with 125I-labelled globin mRNA the plasmids of individual clones were characterized by hybrid arrested cell-free translation. Thus we could isolate clones containing alpha or beta globin chain nucleotide sequences. DNA was isolated from chicken blastoderms incubated for 18-20 h and from 11 d chicken embryos. A comparison of the restriction maps of the DNA from the two developmental stages with labelled nick translated plasmids and labelled cDNA did not indicate any globin gene rearrangements between these two stages of embryonic development. We conclude, that the adult chicken globin genes show a constant genomic organization during embryonic development. However, the restriction patterns of the globin gene family of the chicken strain investigated revealed some differences after 2 generations of propagation.

Animals↗