[Abdominal infection: surgical domain].
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Abdomen↗
Biomedical subjects
Wolfgang H Hartl
Publications and source records attributed to Wolfgang H Hartl.
Isolation of plasma albumin by ethanol extraction is inappropriate for isotope ratio measurements during the acute phase response.
Isolation of high-purity albumin from plasma is essential to study albumin kinetics in vivo with tracer techniques. Because of its simplicity ethanol extraction has been repeatedly used for albumin purification. However, it cannot be excluded that this single-step procedure completely prohibits contamination by other proteins, especially those known to be produced at an accelerated rate during the acute phase response. In the present study, we wanted to examine the reliability of ethanol extraction in different clinical conditions and to study the effects of potential impurities on albumin enrichment during stable isotope tracer studies. SDS-PAGE revealed a contaminating protein band at about 25,000 Da in healthy subjects and postoperative patients during the acute phase response, but not in critically ill patients. According to densitometry about 8% of proteins after ethanol extraction were contaminants. To examine potential contaminant effects on tracer enrichment 1-[13C]-leucine was given to healthy subjects and postoperative patients. Blood samples were taken after various amounts of time, and albumin enrichments (tracer/tracee ratios) were determined from isotope ratios obtained by mass spectrometry. Irrespective of the magnitude of tracer enrichment, postoperative tracer/tracee ratios were significantly higher (on average +10%) in samples exclusively analysed by ethanol extraction than in samples which had undergone additional electrophoretic purification. No significant effect of the contaminant was seen in healthy subjects. N-terminal protein sequencing revealed contaminants to mainly consist of apolipoprotein A-1. Its physiology and pathophysiology may sufficiently explain its variable effects of albumin enrichment. Our findings suggest that exclusive ethanol extraction is inappropriate for albumin isolation in tracer studies performed during the acute phase response. Ethanol extraction may also not be advisable in all other situations known to be associated with a rise in apolipoprotein A-1 turnover.
Acute-Phase Reaction↗
Use of the molecular adsorbent recycling system in the treatment of postoperative hepatic failure and septic multiple organ dysfunction--preliminary results.
PURPOSE OF THE STUDY: Molecular adsorbent recycling system (MARS) has been applied successfully in patients with a variety of liver diseases. However, preliminary results in patients with multiple organ failure (MOF) and sepsis were disappointing, possibly because the number of applied MARS cycles was too low. To determine potential effects of prolonged MARS treatment in patients with postsurgical MOF we evaluated five postoperative patients with acute liver failure and septic multiple organ dysfunction in a retrospective observational study. METHODS: MARS cycles (13.4+/-1.9) were applied during an average time period of 17.2+/-5.2 days. Fresh frozen plasma, thrombocyte units and blood units were transfused to maintain pre-MARS Quick values and thrombocyte counts, and to keep the hemoglobin concentration above 8 g/dl. MAIN FINDINGS: Plasma bilirubin concentrations declined significantly during treatment. In contrast, ammonia concentration remained constant, and parameters of the clotting system (Quick value) did not get better or even worsened (partial thromboplastin time) despite significantly increasing the substitution frequency of coagulatory factors. Due to poor clotting, we observed significant bleeding complications during MARS therapy causing a simultaneous rise in the number of transfused blood units. All patients demonstrated persistent, severe abdominal infection during MARS therapy. After discontinuing MARS treatment because of insufficient efficiency, all patients died of progressive septic organ malfunction. CONCLUSION: Our preliminary findings do not support use of MARS in patients with postoperative hepatic failure and progressive septic multiple organ dysfunction, particularly if the septic focus cannot be eliminated. If MARS is still applied, special attention should be paid to simultaneous clotting disorders and bleeding complications.
APACHE↗
A subset of human dendritic cells in the T cell area of mucosa-associated lymphoid tissue with a high potential to produce TNF-alpha.
Recently, a new class of human dendritic cell (DC) precursors has been described in the peripheral blood recognized by the mAb M-DC8. These cells represent approximately 1% of PBMC and acquire several characteristics of myeloid DC upon in vitro culture. In this report we show that M-DC8(+) monocytes secrete in response to LPS >10 times the amount of TNF-alpha as M-DC8(-) monocytes, but produce significantly less IL-10. Consistent with a role in inflammatory responses, we found that M-DC8(+) cells localized in the T cell area of inflamed human tonsils and in the subepithelial dome region of Peyer's patches. In patients with active Crohn's disease, abundant M-DC8(+) cells were detectable in inflamed ileal mucosa, which were entirely depleted after systemic steroid treatment. Our results indicate that M-DC8(+) cells are cells of DC phenotype in inflamed mucosa-associated lymphoid tissue that may contribute to the high level of TNF-alpha production in Crohn's disease. We infer that selective elimination of M-DC8(+) cells in inflammatory diseases has therapeutic potential.
Anti-Inflammatory Agents↗
Effect of tumor removal on mucosal protein synthesis in patients with colorectal cancer.
It is currently controversial whether mucosal hyperproliferation is involved in colorectal cancerogenesis. The purpose of the present study was to examine protein synthetic rate as an indicator of potential tissue proliferation in grossly normal rectal mucosa from cancer-bearing subjects and to compare this rate with that in mucosa from subjects posttumor removal. Six postabsorptive patients with localized rectal cancer and five postsurgical control subjects received a primed constant infusion of [1-(13)C]leucine (0.16 micromol/kg min, 9.6 micromol/kg prime). Forceps biopsies from the mucosa were taken after 3 and 6 h. Protein synthesis was calculated from protein-bound leucine enrichment (determined by capillary GC-combustion IRMS) and from the enrichment of free intracellular leucine (determined by GC-quadrupole MS). In cancer-bearing subjects, mucosal protein synthesis amounted to 1.28 +/- 0.24%/h. This rate was significantly higher (P < 0.05) than the corresponding rate of mucosa from patients after cancer removal (0.69 +/- 0.09%/h). These findings do not support the concept that colorectal cancer originates from a proliferative disease of the whole colon. Increased mucosal protein synthesis appears to depend on the presence of the tumor itself and should therefore be considered a secondary phenomenon.
Aged↗
Effect of amino acid infusion on human postoperative colon protein synthesis in situ.
BACKGROUND: Amino acids are an integral part of parenteral nutrition because of their anabolic action helping to conserve body protein after surgical stress. At the gastrointestinal tract, an adequate supply of amino acids may be particularly important because of the gut's high rate of protein turnover, cell division, and proliferation. However, no information is available about the effects of amino acids on human intestinal protein metabolism after surgery. METHODS: Studies were performed in postabsorptive patients 8-10 days after major abdominal surgery. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[13C]-leucine into colon mucosal protein. All subjects had a colostomy, which allowed easy access to the colon mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 micromol/kg min). Isotopic enrichments were determined at baseline and after a 4-hour infusion of amino acids or after infusion of saline (control group). RESULTS: Compared with baseline, infusion of amino acids reduced fractional colon protein synthesis significantly by -29.2 +/- 8.3%. This decrease was also significantly different from the corresponding (insignificant) change during saline infusion (+19.4 +/- 26.9%, p < .05 vs amino acid group). CONCLUSIONS: After surgery, an amino acid infusion acutely reduces postoperative colon protein synthesis. This effect possibly may be attributed to interactions of specific amino acids (glutamine) with an altered intestinal immune system and enterocyte activity.
Amino Acids↗
The effect of hyperglycemic hyperinsulinemia on small-intestinal mucosal protein synthesis in patients after surgical stress.
Hyperglycemic hyperinsulinemia cannot stimulate intestinal protein synthesis in healthy individuals but does so in conditions characterized by an altered somatotropic axis such as diabetes. Only in a state of growth hormone resistance (high growth hormone but low insulin like growth factor [IGF-1] concentrations), extra insulin may acutely reverse the impaired, growth-hormone-induced IGF-1 release, thereby exerting anabolic actions at the intestinal tract. Growth hormone resistance can be also found in patients after surgical stress. Therefore, we wanted to test the hypothesis whether hyperglycemic hyperinsulinemia would stimulate ileal protein synthesis in the latter condition. Mass spectrometry techniques (capillary gas chromatography/combustion isotope ratio mass spectrometry) were used to directly determine the incorporation rate of 1-[(13)C]-leucine into ileal mucosal protein. All subjects had an ileostomy, which allowed easy access to the ileal mucosa, and consecutive sampling from the same tissue was performed during continuous isotope infusion (0.16 mumol/kg min). Isotopic enrichments and fractional protein synthesis were determined at baseline (period I) and after a 4-hour glucose infusion (170 mg/kg/h) or after infusion of saline (control group) (period II). In controls, ileal protein synthesis declined significantly during prolonged isotope infusion (period I: 1.11 +/- 0.14%/h, period II: 0.39 +/- 0.13%/h, p < .01). In contrast, ileal protein synthesis remained constant during glucose infusion (period I: 1.32 +/- 0.35%/h, period II: 1.33 +/- 0.21%/h, n.s. vs period I, but p < .005 vs the corresponding value at the end of period II in the control group). Using the continuous tracer infusion technique, ileal protein synthesis seemingly declines over a short time in control subjects. We found evidence that this artificial decline was due to mass effects of a rapidly turning over mucosa protein pool in which an isotopic plateau was reached during the experiment and of which the size amounted to approximately 4% of the total mixed protein pool. Maintenance of ileal protein synthesis during glucose infusion therefore indicates a rise of ileal protein synthesis in a slowly turning over protein pool. This effect in postsurgical patients would be compatible with the concept of intestinal insulin action to depend on the specific clinical state (eg, growth hormone resistance).
Aged↗