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Biomedical subjects

M Oellerich

Publications and source records attributed to M Oellerich.

At least 109 records · Page 6Linked to original sources

Relationship of apolipoproteins AI, B and lipoprotein Lp(a) to hepatic function of liver recipients during the early post-transplant period.

To evaluate serum apo AI, apo B, Lp(a) and the ratio of unesterified cholesterol to total cholesterol as markers of hepatic synthetic capacity after orthotopic liver transplantation, serial measurements of these variables were performed on post-transplant days 1, 3, 5, 7, 10 and 14 in 70 patients. Liver function was assessed by a quantitative dynamic test based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX). Patients were divided into two groups on the basis of clinical and laboratory findings, those with evidence (n = 46) and those without evidence (n = 24) of hepatic dysfunction. Apo AI levels fell in both groups to day 5, but then began to increase in the group with good hepatic function, a highly significant (P < 0.001) positive correlation being found with the results of the MEGX test on post-transplant days 7, 10 and 14. The ratio of unesterified cholesterol to total cholesterol rose in both groups from days 1 to 7 and then began to fall in the group without hepatic dysfunction; a highly significant (P < 0.001) negative correlation was observed with the results of the MEGX test on days 10 and 14, Apo B levels rose in both groups from days 1 to 10, with no significant differences between the two groups; no correlation was observed with the results of the MEGX test on any study day.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Monitoring of TPMT in heart transplant recipients under immunosuppressive therapy with azathioprine.

Azathioprine (AZA) is routinely used in double and triple immunosuppressive therapy after cardiac transplantation. In some cases it causes severe myelosuppression. The interindividual differences in AZA toxicity is probably due to differences in the drug metabolism. Thiopurine methyltransferase (TPMT) is thought to be the most important enzyme in the catabolism of AZA. A deficiency in this enzyme will presumably increase the availability of 6-mercaptopurine for the anabolic pathway thereby leading to increased cytotoxicity. A 65-year-old male underwent heart transplantation at our institution with an uncomplicated course. Immunosuppression consisted of cyclosporine, prednisolone, and AZA. Several weeks after the administration of AZA, the patient developed severe leukopenia. TPMT activity was then measured in this patient and found to be below the detection limit. Subsequently the patient died from multiorgan failure due to septicaemia. As a result of this experience, we started to screen all patients for TPMT deficiency. In 58 healthy controls, the mean activity was found to be 11.8 nmol/h/ml of red blood cells (RBC) while in 13 patients on our waiting list, the mean activity was found to be 11.97 nmol/h/ml of RBC. In 15 patients after heart transplantation and azathioprine treatment, the mean activity was found to be 17.2 nmol/h/ml of RBC. We suggest screening for TPMT activity in transplant patients with leukopenia under AZA therapy. If TPMT deficiency is present, the AZA dosage should be adjusted or alternative immunosuppressive regimens should be considered.

Aged↗

Influence of gender on the monoethylglycinexylidide test in normal subjects and liver donors.

The objective of this study was to investigate the effect of gender on monoethylglycinexylidide (MEGX) formation in normal subjects and cadaveric liver donors. The study included 92 male and female healthy volunteers < 45 years of age and 98 age- and sex-matched liver donors from a previous study, whose livers were used for transplantation. Women < 45 years not taking contraceptives showed significantly lower MEGX concentrations 30 min after lidocaine administration than men [median (16-84th percentile)]: 59 micrograms/L (41-70 micrograms/L) versus 81 micrograms/L (58-98 micrograms/L)]. The lowest MEGX 30 min values were observed in women taking contraceptives: 39 micrograms/L (25-48 micrograms/L). Intraindividual variability of serial MEGX tests was moderate (median: 17.8%, n = 8) when measured in female subjects taking no contraceptives and males. Cadaveric liver donors showed significantly higher MEGX 15 and 30 min values compared with normal subjects (p < or = 0.0001). There was no statistically significant difference between MEGX values obtained in male and female cadaveric donors. The urinary excretion of MEGX was similar in male and female normal subjects. Our results suggest that sex-related differences in MEGX formation as well as the influence of contraceptives have to be taken into account when test results from living related liver donors and patients with less advanced chronic liver disease are evaluated. In cadaveric liver donors, however, sex-related differences do not affect MEGX formation.

Adult↗

Plasma lipids are not oxidized during hemodialysis.

Lipid peroxidation products, both lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS) were determined in the plasma of 31 uremic patients treated with maintenance hemodialysis. Whereas patients had significantly elevated TBARS compared to 93 healthy controls (4.25 +/- 1.53 vs. 1.66 +/- 0.50 mumol/l; p < 0.01) lipid hydroperoxides were not detected in the plasma of patients before dialysis. After hemodialysis, a slight increase in TBARS was observed (4.50 +/- 1.97 mumol/l, p > 0.01). However, when the TBARS were corrected for hemoconcentration by relating TBARS to the plasma cholesterol concentrations a statistically significant decrease of TBARS was observed (1.02 +/- 0.63 mumol TBARS/mmol cholesterol vs. 0.84 +/- 0.60 mumol TBARS/mmol cholesterol; p < 0.01) after 240 min of hemodialysis. There was no evidence for the formation of plasma lipid hydroperoxides in the extracorporeal circulation. It is therefore suggested that elevated TBARS in chronic renal failure are not caused by the dialysis therapy.

Adult↗

Determination of a fragment of the c-erbB-2 translational product p185 in serum of breast cancer patients.

Concentrations of a fragment of the c-erbB-2 translational product (p185 fragment) were measured in serum of 70 breast cancer patients, 19 healthy blood donors, and 18 pregnant women using a heterogenic enzyme immunoassay. The serum concentrations of blood donors and pregnant women were below 30 kU/l. Breast cancer patients showed serum concentrations up to 578 kU/l. All 9/70 patients with serum concentrations higher than 30 kU/l had clinical evidence of metastatic disease and the serum levels of all 35/70 patients without metastasis lay within the normal range. From 9/37 patients with p185 overexpression of the primary tumor in immunohistochemical analysis 3/9 patients with metastatic disease had elevated serum levels higher than 30 kU/l. In all, 6/9 patients without metastasis serum levels were below 30 kU/l. The data of the present study suggest that determination of serum p185 fragment concentrations may be useful as a diagnostic tool in postoperative follow-up of breast cancer patients with c-erbB-2 overexpression of the primary tumor.

Biomarkers, Tumor↗

Oxidative modification of low density lipoproteins by human polymorphonuclear leukocytes.

Oxidatively modified low density lipoproteins are thought to play an important role in the generation of macrophage-derived foam cells in early atherosclerotic lesions. Cultured endothelial cells, monocytes, macrophages and smooth muscle cells can modify low density lipoproteins, either by a free radical mechanism or by the action of lipoxygenases. Previous studies demonstrated that activated human polymorphonuclear leukocytes can oxidize low density lipoprotein lipids. Stimulation of the cells with phorbol 12-myristate 13-acetate resulted in an increase both in superoxide anion production and in low density lipoprotein oxidation. The present results show that the oxidative modification of low density lipoproteins by human polymorphonuclear leukocytes can be inhibited by superoxide dismutase but not by the lipoxygenase inhibitor, (5,8,11,14)-eicosatetraynoic acid. The low density lipoproteins oxidized by polymorphonuclear leukocytes were recognized by the scavenger receptor of macrophages (P 388 cell line). It is proposed that the superoxide anion is an important factor in the oxidative modification of low density lipoproteins induced by polymorphonuclear leukocytes, and that under conditions of increased oxidative metabolism in vivo, polymorphonuclear leukocytes can contribute to foam cell formation by a scavenger receptor-dependent process at lesion sites.

5,8,11,14-Eicosatetraynoic Acid↗

Changes in energy substrates in relation to arterial ketone body ratio after human orthotopic liver transplantation.

BACKGROUND: Changes in energy substrate metabolism, as well as those in arterial ketone body ratio (KBR; acetoacetate/3-hydroxybutyrate), were investigated to follow energy status of hepatic allograft. METHODS: Plasma concentrations of energy substrates were measured immediately after 35 orthotopic liver transplantations in 32 adult patients. RESULTS: Twenty-three patients left the intensive care unit within 1 month (group A), six patients were forced to stay in the intensive care unit longer than 1 month (group B), and the other six grafts failed within 1 month (group C). In group B the KBR was significantly lower than in group A 6 hours after reperfusion of the grafts (0.70 +/- 0.09 vs 1.21 +/- 0.10, mean +/- SEM; p < 0.05). In group C the KBR remained significantly lower than in group A at 6 hours (0.65 +/- 0.04 vs 1.21 +/- 0.10; p < 0.01), on the first postoperative day (0.64 +/- 0.03 vs 1.36 +/- 0.10; p < 0.001), and on the second postoperative day (0.65 +/- 0.02 vs 1.58 +/- 0.11; p < 0.01). Total ketone body concentration (TKB) was significantly higher in group B than in group A at 4 hours (462.9 +/- 105.0 mumol/L vs 201.6 +/- 32.6 mumol/L; p < 0.01), 6 hours (483.4 +/- 102.1 mumol/L vs 125.5 +/- 25.9 mumol/L; p < 0.001), and the first postoperative day (481.1 +/- 196.6 mumol/L vs 123.9 +/- 24.1 mumol/L; p < 0.001). No increase in TKB was observed in group C. CONCLUSIONS: It is suggested that low values in KBR accompanied with low levels of TKB should be regarded as a strong indicator of graft failure and fatty acid oxidation and ketogenic pathways are accelerated to compensate for energy deficits in patients with low values in KBR and high levels of TKB until KBR recovers immediately after orthotopic liver transplantation.

Acyl Coenzyme A↗

[Changes in liver function and morphology after various portocaval bypass operations].

Using an experimental animal model consequences of operatively changed modes of liver perfusion on hepatic function could be demonstrated. Three groups of 5 animals each (swine) had the following operations: Group I received a portocaval shunt. In group II in addition to the portocaval shunt a vein graft was interposed between the vena cava and the portal vein. In group III an arterialization of this graft was performed in addition to the two operations mentioned above. Follow-up at defined time intervals included clinical, laboratory and histological data. It could be demonstrated that animals in group II and III showed normal parameters as far as behavior and controlled lab data are concerned. Animals of group I had significantly poorer results in all tests. In this study we found that direct portal perfusion was not necessary for a normal liver function and could be fully compensated both by caval venous blood and by arterialized caval venous blood.

Animals↗

Receiver operating characteristic (ROC) analysis of the ability of arterial ketone body ratio to predict graft outcome after liver transplantation--its sensitivity and specificity.

To evaluate the ability of arterial ketone body ratio (AKBR; acetoacetate/3-hydroxybutyrate) to predict graft prognosis after liver transplantation, the diagnostic value as a predictive index was compared between AKBR and conventional liver function tests using receiver operating characteristic (ROC) analysis. The ROC curves were determined for AKBR, GOT, GPT, total bilirubin, serum lactate level, and prothrombin time, all of which were measured on the 1st and 2nd postoperative days in 88 cases of liver transplantation. Comparisons of the areas under the ROC curves between AKBR and other tests revealed the significant superiority of AKBR to other tests in predicting graft death within 1 month after transplantation. The present study suggests that AKBR can be used as an accurate index to predict graft prognosis after liver transplantation.

Adolescent↗

Pre- and post-transplant assessment of liver function in paediatric liver transplantation.

The pre-operative risk of paediatric liver transplantation candidates (n = 41) was assessed in a prospective study by means of clinical symptoms, conventional static and liver blood flow dependent dynamic liver function tests. Nine patients died during the 365-day waiting period. The data were subjected as covariates to a survival analysis in the Cox proportional hazards model. There was a significant relationship between the results of mono-ethylglycinexylidide (MEGX) formation and ICG test and the 365-day survival rate. In the stepwise analysis, none of the remaining parameters improved the predictive ability when added to the dynamic liver function test results. The assessment of post-transplantation liver function was studied in 27 patients during the first 28 postoperative-day period. In addition, liver function was studied in a cross-sectional study 1-7 years after successful liver transplantation in children with complete or partial rehabilitation. In the early postoperative period severe organ damage was indicated by both static and dynamic liver function tests. In the later course after transplantation no deterioration of liver function measured with MEGX formation was to be observed. These findings demonstrate the usefulness of dynamic liver function tests in the pre- and post-transplant assessment of liver function.

Child↗