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Biomedical subjects

M Heberer

Publications and source records attributed to M Heberer.

At least 109 records · Page 6Linked to original sources

Protective effect of allopurinol and superoxide dismutase in renal isografts in cyclosporin A-treated rats.

Acute tubular necrosis (ATN) after renal transplantation is related to the duration of warm and cold ischemia and leads to temporary or permanent impairment of graft function. An increased incidence of ATN has been reported since the introduction of cyclosporin A. Kidney damage resulting from hypothermic storage is generated in part during reperfusion rather than during ischemia itself. Potential mediators of the reperfusion injury are oxygen-derived free radicals. Therefore, the influence of two oxygen radical antagonists, allopurinol and superoxide dismutase, was evaluated in syngeneic rat kidney transplantation with and without concurrent administration of cyclosporin A. At 15 h cold ischemia, 28-day survival increased from 8% (no treatment) to 22% (superoxide dismutase), 33% (superoxide dismutase and allopurinol), and 73% (allopurinol). Cyclosporin A cotreatment (10 mg/kg over 14 days) resulted in survival rates of 0%, 25%, 17%, and 50% for the respective treatment groups. The results of serum creatinine values and morphological evaluation of biopsies paralleled the survival rates. Cyclosporin A nephrotoxicity was evidenced by significant serum creatinine elevations throughout the 28-day period of observation. In conclusion, allopurinol significantly protects syngeneic rat kidney transplants against a critical duration of cold ischemia. Under the conditions of this experiment, allopurinol was clearly superior to superoxide dismutase treatment. Cyclosporin A nephrotoxicity was, however, not ablated by the oxygen radical antagonists employed.

Allopurinol↗

Quantification of absorption, intestinal and hepatic first pass effect in a chronic dog model.

A chronic dog model was used to measure the absorption and to elucidate the site and extent of presystemic metabolism of a selective D1-agonist (CY 208-243). The dog was instrumented with portal vein and carotid artery catheters together with an electromagnetic flow measuring device around the portal vein. After administering [14C]CY 208-243 intrajejunally, absorption rate was defined as the product of porto-arterial substrate difference and portal venous blood flow. The extent of absorption amounted to 34% for total radioactivity and 31% for unchanged drug, this indicating a gastrointestinal first-pass of 9%. In an additional study [14C]CY 208-243 was injected intravenously to the dog; the absorption (29%) and the bioavailability (5%) of CY 208-243 were calculated from the ratio of dose normalized, oral versus intravenous AUC values for total radioactivity and unchanged drug, respectively. These data confirm the absorption value found with the chronic dog model and indicate a global presystemic, i.e. intestinal and hepatic, first-pass effect of 83%. In conclusion, this chronic dog model allows an accurate assessment of drug absorption and a quantification of the gastrointestinal and hepatic first-pass effects.

Administration, Oral↗

[Enteral nutrition at home with jejunostomy catheter].

Ten patients with obstructive tumors of the upper gastrointestinal tract received a catheter jejunostomy (CJ) for long periods of enteral nutritional support. Seven of those patients received home enteral nutritional support for a period of 2-9 months. Body weight and serum albumin remained constant during the nutritional therapy. Complications (diarrhea, leakage) were rare and could successfully treated without interruption of feeding. In our experience CJ is a safe and effective method for home enteral nutritional support.

Catheters, Indwelling↗

[Financial planning for surgical research. Project portfolio as an instrument for research planning].

Planning of research funding should assure both volume and continuity of economic support. Funding of new research concepts usually depends largely on the internal budget of the research institution (primary economical resources). More mature projects can be funded by governmental and non-profit (secondary) or industrial sources (tertiary economical resources). In general, a balanced proportion of financial support will assure maximal research independence. The respective funding of a research project should be regarded as extrinsic to the quality of the said project. Portfolio analysis of research projects is introduced as a new means of planning and controlling academic and industrial research. In principle, research projects will be evaluated with regard to the inherent potential of development (e.g. potential impact on clinical or scientific concepts) and the current productivity (e.g. output of results and publications). The 2-dimensional portfolio-matrix will be used to analyse these factors, manifesting both the overall activity of a research unit and the development of new research and funding strategies. In addition, repetitive project-portfolio analyses will enable control of both spending and efficiency in research. The application of the current project-portfolio method is exemplified by an analysis of the research activities of the department of surgery at the university of Basel. To date, project-portfolio analysis is not a mature method: Development of more quantitative portfolio strategies and of multidimensional project-portfolios are proposed. However, project-portfolio analysis is a promising means of planning and controlling research. It should be used and developed further in institutions with a number of concurrent research activities.

Animals↗

[Reduction of renal reperfusion damage following warm ischemia by allopurinol and superoxide dismutase].

Preserved organs are damaged not only by the ischemic injury due to lack of oxygen. The reperfusion injury mediated by oxygen free radicals is an important factor in the postischemic organ failure. The prevention of free radical-induced reperfusion injury with allopurinol (AP) and superoxide dismutase (SOD) is shown in a warm ischemia kidney model. Rats were treated with allopurinol (40 mg/kg i.v.) one hour, or with SOD (20,000 IU/kg i.v.) one minute before reperfusion after a period of 35 minutes of warm ischemia. Allopurinol and SOD reduced significantly the postischemic kidney failure with a less important increase of creatinine. Creatinine levels on day three in the control group: 517 +/- 87 mumol/ml, in the SOD-group: 206 +/- 105 mumol/ml, and in the AP-group: 163 +/- 81 mumol/ml (anal. of variance: p = 0.0001). AP has a wide therapeutic range. We feel, that it is important to confirm the prevention of reperfusion injury by allopurinol prophylaxis clinically.

Allopurinol↗

[Preoperative assessment of at-risk patients in traumatology].

In a randomized, prospective double blind trial evaluating antibiotic prophylaxis for internal fixation of proximal femur fractures, the prognostic value of preoperative risk parameters, namely triceps skinfold, upper arm circumference, dynamometry, serum albumin, transferrin, prealbumin, lymphocyte count and serum zinc was analyzed. A population at risk of postoperative infection could be defined with serum albumin value and lymphocyte count: a serum albumin of less than 40 g/l correlated with increased local complications and a lymphocyte count under 1400 microliters coincided with increase in systemic infections. No correlation between perioperative transfusion and postoperative infections was found.

Aged↗

Absorption of protein in the early postoperative period in chronic conscious dogs.

Postoperative alterations in amino acid exchange across the intestinal tract and in the capacity for protein absorption were investigated in a chronic canine model. Changes in postoperative splanchnic amino acid exchange consisted of a temporary decrease of total splanchnic amino acid release, including a significant reduction in alanine production, and an increase in glutamine consumption. Contrary to results under stable metabolic conditions, branched chain amino acids were also taken up by the intestine in the early postoperative period. The changes in postoperative amino acid exchange were not, however, reflected by a corresponding alteration in protein transport capacity. The absorptive capacity for a protein hydrolysate remained stable during the early postoperative period.

Amino Acids↗

Indications for needle catheter jejunostomy in elective abdominal surgery.

Needle catheter jejunostomy for postoperative nutritional support is now employed worldwide. However, there is a large discrepancy regarding indications for this technique which this study attempts to rectify. The need for nutritional support after elective abdominal procedures in 464 patients was analyzed and compared with the experience with needle catheter jejunostomy in 42 patients. The results show that needle catheter jejunostomy is indicated after extensive operations of the upper gastrointestinal tract, for example, esophagectomy, total gastrectomy, and the Whipple procedure. With minor upper gastrointestinal operations, or procedures of the lower gastrointestinal tract, needle catheter jejunostomy should be performed only in patients with poor nutritional status or in the presence of postoperative chemotherapy or radiotherapy. In an unclear situation, liberal insertion of the needle catheter jejunostomy and a postponed decision on enteral feeding is recommended, as there is no significant catheter-related morbidity.

Abdomen↗

[Autologous spongiosa as an antibiotic carrier in the treatment of osteitis].

The treatment of osteomyelitis essentially depends on a bactericidal concentration of antibiotic in bone tissue with an appropriate spectrum. Ciprofloxacin is effective against the main organisms causing osteomyelitis (staphylococcus aureus, pseudomonas aeruginosa) at low MIC. We investigated the concentration of ciprofloxacin in human bone. After a single dose (200 mg ciprofloxacin i.v., preoperatively) the concentration in cortical bone was 6.9 +/- 0.8 mcg/g and 9.7 +/- 0.8 mcg/g in cancellous bone. In any case the concentration of ciprofloxacin exceeded the MIC for staph. aureus and pseudomonas aeruginosa. For the treatment of osteomyelitis we transferred the antibiotic bound to autologous cancellous bone grafts to the site of inflammation after surgical debridement. First clinical results are documented.

Administration, Topical↗

The effect of surgery and anesthetic agents on granulocyte-chemiluminescence in whole blood.

The effect of anesthesia and major abdominal surgery on zymosan-induced chemiluminescence (CL) of neutrophil granulocytes was evaluated. CL was measured in diluted whole blood taken at distinct intervals within the perioperative period. In addition, blood samples from healthy volunteers were supplemented with ether and halothane to investigate the in vitro effect of these agents. The phagocytosis-induced CL was not found to be depressed by anesthesia and surgery. Only at supranarcotic concentrations was CL reduced. Surgery and anesthesia, therefore, do not appear to impair this defense system significantly under the conditions of this investigation.

Abdomen↗

Development of a chronic canine model for measurement of absorption by substrate appearance in portal venous blood.

Research in absorption physiology requires animal models which closely resemble the in vivo situation. The description of a new canine model satisfying these requirements is the objective of this report. Dogs were instrumented with indwelling portal vein and carotid artery catheters, a catheter jejunostomy and an electromagnetic flow measuring probe around the portal vein enabling continuous flow recordings. Following intrajejunal infusion of nutritive substrates in the conscious animal, absorption was measured as the product of porto-arterial substrate difference and portal venous flow. The model was validated in five mongrel dogs: (1) Catheters and flow measuring device function over several months. (2) The sensitivity of the method was evaluated following intrajejunal infusion of l-glycine-l-tyrosine and its constituent amino acids. A significant portoarterial concentration difference of both amino acids enabling quantitative measurement of absorption resulted when the peptide was infused at 4 mmoles/hour (20 mM solution, 200 ml/h). (3) Infusion of complete nutritive formulas caused a significant increase in portal venous flow whereas neither saline nor the amino acids or the peptides investigated had a comparable effect. (4) A validation experiment by implantation of a second flow probe distal to the chronically implanted device provided evidence that granulomatous tissue forming around the probe does not alter the accuracy of the flow recording. In summary, this method permits for the first time quantitative measurement of absorption by appearance rates in portal venous blood instead of by disappearance from the intestinal lumen.

Amino Acids↗

[Catheter jejunostomy in elective abdominal surgery].

Needle catheter jejunostomy is used to a varying extent today. Therefore, the need for nutritional support was evaluated following elective abdominal surgery and compared to experiences with postoperative enteral feeding. Oesophagectomy, total gastrectomy and the Whipple procedure were identified as good indications for catheter jejunostomy, whereas with other types of operation an individual decision is required.

Catheters, Indwelling↗