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C Murr

Publications and source records attributed to C Murr.

43 records · Page 3Linked to original sources
PubMed1993

[Effects of short-term application of recombinant human growth hormone on urea production rate in patients in the early postoperative phase].

OBJECTIVE: To determine the effect of short-term recombinant human growth hormone (rhGH) administration on urea production rate (UPR), N balance and aminograms. DESIGN: Prospective, double-blind placebo-controlled study. SETTING: Intensive care unit of a University Hospital. PATIENTS: 20 adult patients after major abdominal surgery. INTERVENTIONS: Postoperative substitution of rhGH (Saizen, Serono, Aubonne, CH) in a dose of 0.15 IE/kg BW for 3 days. The serum levels of hGH, insulin-like growth factor-1 (IGF-1), ACTH and cortisol were measured as well as the amino acids in plasma. The degree of catabolism was calculated according to Woolfson's formula, which is based on the UPR, and by calculation of the cumulative N balance. RESULTS: With exception of proline, the plasma amino acids between the groups receiving active substance and total parenteral nutrition (TPN) and those receiving placebo and TPN did not differ significantly. Neither was there a significant difference between the groups for any other parameter measured. The UPR and IGF-1 levels showed only a tendency towards higher values as compared with the placebo group (UPR verum group, values in g/day: 1st measurement, 29.8 +/- 16.7; 2nd measurement, 28.3 +/- 17.7; 3rd measurement, 32.1 +/- 19.1; 4th measurement, 33.1 +/- 21.2. UPR placebo, values in g/day; 1st measurement, 32.6 +/- 23.9; 2nd measurement, 30.8 +/- 17.9; 3rd measurement 41.6 +/- 28.7; 4th measurement, 47.3 +/- 29.5. IGF-1 verum group, values in nmol/l; 1st measurement, 25.7 +/- 19.2; 2nd measurement, 44.8 +/- 23; 3rd measurement, 52.4 +/- 30; 4th measurement, 54.3 +/- 20. IGF-1 placebo, values in nmol/l; 1st measurement: 22.9 +/- 11.7; 2nd measurement, 37.0 +/- 19.4; 3rd measurement, 38.4 +/- 21.4; 4th measurement, 40.0 +/- 23.0). The ACTH-cortisol axis was only slightly depressed in the group receiving active substance. CONCLUSIONS: We conclude that short-term rhGH administration over 3 days is not capable of significantly reducing the UPR in postoperative patients, but we cannot exclude a significant difference between rhGH group and placebo after a longer administration period.

Abdomen↗
PubMed1992

[Gliadin IgA antibodies in diagnosis of celiac disease in childhood].

An enzyme immunoassay kit for the determination of anti-gliadin-IgA antibodies in serum has been evaluated in the diagnosis of coeliac disease in childhood. 84 patients, 22 of them with coeliac disease according to ESPGAN's criteria were tested between 1978 and 1989 and the results have been correlated with the findings on small intestine biopsy and the clinical features. The sensitivity of the test was 95.5% and the specificity was 87.0% on initial diagnosis. On a gluten-free diet reduced antibody levels were seen in all patients. During gluten challenge 11 of 13 children showed an increase in anti-gliadin-IgA concentration. Of the remaining 2 without antibody elevation IgA deficiency became manifest in one patient, the other had a nearly normal mucosa on small intestine biopsy. Provided that IgA deficiency is ruled out and the gluten intake is sufficient the test seems to be useful for screening and might replace biopsy after gluten challenge in cases of increasing antibody levels.

Biopsy↗
PubMed1990

Purine metabolism of human glioblastoma in vivo.

The aim of this study was to identify targets for rational chemotherapy of glioblastoma. In order to elucidate differences in the biochemistry of tumor and normal human brain, in vivo pool sizes of purine nucleotides, nucleosides, and nucleobases and of purine metabolizing enzymes in biopsy material from 14 grade IV astrocytomas and 4 normal temporal lobe samples were analyzed. Specimens were collected during surgery using the freeze-clamp sampling technique and analyzed by high pressure liquid chromatography. Total purine nucleotides, adenylates, and guanylates in the tumors were 2186, 1865, and 310 nmol/g (wet weight), respectively, which corresponds to 61, 60, and 71% of normal brain tissue concentrations. Relative to normal brain the tumors had significantly lower ATP and GTP levels, essentially normal pool sizes of purine nucleosides and bases, unchanged activities of the salvage enzymes hypoxanthine-guanine phosphoribosyltransferase, adenine phosphoribosyltransferase, and adenosine kinase (659, 456, and 98 nmol/h/mg protein, respectively) and 4-fold higher activities of IMP dehydrogenase (11.6 nmol/h/mg protein); the latter is the rate limiting enzyme for guanylate de novo synthesis. IMP pools in the tumors were 64% of values in normal brain. Modulation of the guanylate pathway in glioblastoma by inhibition of IMP dehydrogenase with tumor specific agents such as tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) appears to be a rational therapeutic approach. Preliminary in vitro experiments with normal and malignant tissue specimens from 2 additional patients revealed that significant amounts of the active metabolite thiazole-4-carboxamide adenine dinucleotide are formed from tiazofurin. At a concentration of 200 microM this drug was able to deplete guanylate pools in the tumors to a median of 54% of phosphate buffered saline treated controls. Flux studies with [14C]formate showed that tiazofurin strongly inhibited de novo synthesis of guanylates in glioblastoma to an average of 10% of controls. This effect was more pronounced in the tumors as compared to normal brain. No inhibition of salvage of [14C]guanine by tiazofurin could be observed in normal and malignant tissues. Supportive measures have to be considered to inhibit the highly active salvage enzyme hypoxanthine-guanine phosphoribosyltransferase that can partly antagonize a tiazofurin induced decrease in guanine nucleotides.

Brain↗
PubMed1990

Effect of the calcium entry blocker nimodipine on the metabolism of nucleic acids in rat brain ischemia.

The effect of nimodipine, a 1,4 dihydro-piridine calcium entry blocker (200 micrograms/kg), was investigated in rats after definitive ischemia or 2 min of global ischemia (neck tourniquet method). The brains were freeze-clamped at the desired time intervals and subjected to high pressure liquid chromatography analyses for nucleotides and enzymatic lactate estimation. Although in the definitive ischemia (removal of the brain) no difference was observed in the treated versus the untreated animals, there was a statistically significant difference in both groups after global ischemia followed by reperfusion. Thirty minutes after reflow the brains of the treated animals contained 1,690 +/- 62 nmol ATP/g as compared to 765 +/- 259 nmol ATP/g in the untreated animals (p less than 0.05). The normal controls amounted to 1,932 +/- 77 nmol ATP/g. Also the adenylate energy charge returned to normal in the treated animals (treated animals and controls 0.69 and 0.72, respectively). From these preliminary data we conclude that nimodipine is able to restore mitochondrial function after ischemia and to maintain a high level of energy-rich phosphates. Thus, calcium entry blockers may be effective in preserving and protecting cerebral tissue from irreversible injury after ischemia.

Adenine Nucleotides↗
PubMedDate not supplied

Odd-numbered long-chain fatty acids in propionic acidaemia.

UNLABELLED: In patients with propionic acidaemia (PA), the increased intracellular concentration of propionyl-CoA leads to a relative abundance of odd-numbered long-chain fatty acids (OLCFAs) in body lipids. We investigated the relative amount of OLCFA in erythrocyte membrane lipids over a period of 1-8 years in five patients with early onset PA and present their clinical outcome. After extraction from erythrocyte membrane lipids and esterification, fatty acids were analysed by capillary column gas chromatography. The sum of the OLCFA 15- and 17- carbon saturated and 17-carbon monounsaturated fatty acids (C15:0, C17:0, C17:1) was calculated and expressed as a percentage of the total C14-C22 fatty acids in the sample. Three patients (pccBC-complementation group) presented with a stable clinical course and showed OLCFA values usually below 1.9% (median % +/- SD: 1.4+/-0.5, 1.6+/-0.5, 1.8+/-0.5). Two patients (pccA-complementation group) had a more severe course of the disease and showed higher medians and a broader range of OLCFA levels (2.2+/-1.2 and 2.2+/-0.8). CONCLUSION: Our study shows that odd-numbered long-chain fatty acid concentrations are increased in patients with propionic acidaemia and are higher in those with a more severe clinical course. The value of odd-numbered long-chain fatty acids in the assessment of the phenotypic severity and in the management of propionic acidaemia remains to be proven in a prospective long-term study with more patients of differing phenotype.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

Increased neopterin concentrations in patients with cancer: indicator of oxidative stress?

In vitro, large amounts of neopterin are produced by human monocytes/macrophages upon stimulation with interferon-gamma. In vivo increased neopterin concentrations in human serum and urine indicate activation of cell-mediated (Th1-type) immune response, e.g., during virus infections, autoimmune diseases, allograft rejection and in certain types of malignancy. In various groups of patients with malignant diseases neopterin concentrations correlate to the stage of disease, and higher neopterin concentrations in serum, urine or ascitic fluid were shown to significantly predict worse prognosis regarding relapse and survival. The amounts of neopterin produced by activated monocytes/macrophages correlate with their capacity to release reactive oxygen species (ROS). With this background, neopterin concentrations in body fluids can be regarded as an indirect estimate of the degree of oxidative stress emerging during cell-mediated immune response. Moreover, recently neopterin was found itself to be capable of enhancing toxic effects induced by ROS. In vitro, neopterin derivatives were able to interfere with intracellular signal transduction pathways involved in, e.g., programmed cell death and the induction of proto-oncogene c-fos or nuclear factor-chi B. The data support the view that increased production of ROS--indicated by increased neopterin concentrations--could modulate the development, the proliferation and the survival of malignant cells.

Anemia↗