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Biomedical subjects

H Heidemann

Publications and source records attributed to H Heidemann.

14 recordsLinked to original sources
PubMed1992

Effect of amphotericin B on hepatic cytochrome P-450 and glucose-6-phosphatase in the rat.

The effect of amphotericin B on hepatic microsomal cytochrome P-450 (P-450) concentration was measured in vitro, in vivo and ex vivo in the rat. In vitro, both amphotericin B (0-500 micrograms/ml) and its vehicle, sodium deoxycholate (0-410 micrograms/ml), caused similar dose-dependent decreases of P-450 concentrations and glucose-6-phosphatase activity. Intravenous amphotericin B (3 mg/kg) given daily for 3 days decreased antipyrine clearance from control values of 1.24 +/- 0.24 ml/min to 0.67 +/- 0.12 ml/min (p less than 0.001); whereas antipyrine clearance was unchanged by sodium deoxycholate. The P-450 concentration on the third day was reduced from 0.74 +/- 0.14 nmol/mg protein in control rats to 0.33 +/- 0.09 nmol/mg protein in rats treated with amphotericin B (p less than 0.001). Sodium deoxycholate had no effect on P-450 concentration. In contrast, amphotericin B had no effect on either antipyrine clearance or P-450 concentration following enzyme induction by phenobarbital. Amphotericin B had no effect on microsomal glucose-6-phosphatase activity in vivo. Neither amphotericin B nor sodium deoxycholate induced lipid peroxidation, measured as malondialdehyde production. These results show that amphotericin B decreases hepatic cytochrome P-450 content and function in the rat. These effects can not be observed in the enzyme induced state. Amphotericin B has no effect on glucose-6-phosphatase in vivo, the key enzyme of the gluconeogenesis, indicating selective effects on hepatic microsomal function.

Amphotericin B↗
PubMed1992

Predictability of the in vivo metabolism of verapamil from in vitro data: contribution of individual metabolic pathways and stereoselective aspects.

In vitro studies of drug metabolism with human liver microsomes can be performed in the early stages of drug development. Such experiments may reflect the in vivo metabolism of drugs in humans and thus allow for a prediction of drug disposition before the compound is administered to humans. We tested this hypothesis for the example of verapamil, which is a calcium channel blocker that undergoes extensive metabolism. Moreover, the drug is administered as a racemate, and stereoselective first-pass metabolism favoring the extraction of the more potent S-verapamil is observed after p.o. administration. To evaluate the in vitro metabolism, microsomes prepared from 10 human livers were incubated with both S- and R-verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[In vivo 31-phosphorus magnetic resonance spectroscopy of liver diseases].

31P-MR spectroscopy was performed in 12 patients with focal and diffuse liver disease and in ten normal controls, using surface coils. Results so far show a significantly increased concentration of PME/beta-ATP and of PDE/beta-ATP in patients with liver metastases and in one patient with hepatic involvement by malignant lymphoma. The spectra of liver cirrhosis and fatty livers showed no characteristic changes.

Adult↗
PubMed1987

Amphotericin-B nephrotoxicity in humans decreased by sodium supplements with coadministration of ticarcillin or intravenous saline.

Previous observations suggest that salt loading can help reverse amphotericin-B induced nephrotoxicity. Evidence is presented indicating that sodium supplements provide prophylaxis against the development of amphotericin-B nephrotoxicity. In a retrospective study at Vanderbilt University, 14/21 patients receiving amphotericin B (target dose, 25 mg/day) without salt supplements developed impaired renal function; in 10 instances amphotericin B was temporarily withdrawn. In contrast, only 2/17 patients who received amphotericin B with ticarcillin (with its obligatory sodium supplement) developed nephrotoxicity (P less than 0.01). All four patients, who were receiving the combination of amphotericin B and ticarcillin and who had their ticarcillin therapy stopped, developed nephrotoxicity in the subsequent week. In a prospective observational study at Essen, 20 patients had 24 courses of amphotericin B (target dose, 40 mg/day) with routine supplementation of 1 liter of 0.9% sodium chloride daily. Only two patients showed evidence of nephrotoxicity and no dosage modification of amphotericin B was required in any patient. Four patients with initial evidence of mildly impaired renal function received full supplements without adverse effects or the development of nephrotoxicity. These observations suggest that routine parenteral administration of sodium supplements can help minimize the nephrotoxic potential of amphotericin B.

Amphotericin B↗
PubMed1987

Nitrendipine/digoxin interaction.

The effect of nitrendipine in two different dosages on digoxin plasma levels, urinary recovery, and systolic time intervals was investigated in eight healthy volunteers. Following an adequate loading dose of the glycoside, 0.25 mg digoxin twice daily was given alone for 2 weeks orally. After that, 0.25 mg digoxin twice daily was administered for two 1-week periods combined with nitrendipine, 10 mg or 20 mg once daily. The study was completed with a second digoxin monotherapy phase lasting seven days. Nitrendipine, 20 mg daily, led to a significant increase of the digoxin plasma concentration and of its area under the plasma concentration-time curve (AUC0-12) compared with digoxin monotherapy. Thus, AUC0-12 was 9.7 +/- 0.75 ng ml-1 h (X +/- SEM) when digoxin was given alone and was 11.2 +/- 0.92 ng ml-1 h under coadministration of the calcium antagonist (p less than 0.05). Nitrendipine in the dosage of 10 mg once daily caused a small, insignificant tendency to elevate digoxin plasma levels. In conclusion, nitrendipine, 20 mg daily, causes a significant increase of digoxin plasma concentration and of its AUC, which in certain patients might be of clinical relevance.

Adult↗
PubMed1987

[Prevention of nephrotoxicity of amphotericin B during the treatment of deep candidiasis].

Previous observations suggest that tubulo-glomerular feedback could be involved in amphotericin B nephrotoxicity. We then investigated the influence of sodium status on the occurrence of renal damage during amphotericin B therapy. A retrospective survey demonstrated that impaired renal function occurred during therapy in 67 per cent of the patients who received amphotericin B alone and in 12 per cent of the patients who received amphotericin B and ticarcillin (parenteral sodium supplement of 100-150 meq per day). Prospective studies were then undertaken both in adults and children. Intravenous sodium supplement was given intravenously as routine prophylaxis with amphotericin B therapy. In all courses amphotericin B was successfully administered without deterioration in renal function. These results support the hypothesis that parenteral sodium supplementation reduces the frequency of developing impaired renal function during amphotericin B therapy.

Adult↗
PubMed1986

Effect of two different doses of nitrendipine on steady-state plasma digoxin level and systolic time intervals.

The effect of two different doses of nitrendipine on plasma digoxin levels, urinary recovery and systolic time intervals was investigated in 8 healthy volunteers. Following a loading dose, digoxin 0.25 mg b.d.p.o. was given alone for 2 weeks. Then 0.25 mg digoxin b.d. was administered for two 1-week periods combined with nitrendipine 10 mg or 20 mg once daily. The study was completed with another digoxin monotherapy phase lasting 7 days. Nitrendipine 20 mg daily led to a significant increase in plasma digoxin levels and in its area under the plasma concentration-time curve AUC (0-12) was 9.7 ng ml-1h when digoxin alone was given and 11.2 ng ml-1h on co-administration of the calcium antagonist. Urinary recovery and renal clearance of digoxin were slightly but not significantly increased by nitrendipine. Nitrendipine 10 mg once daily caused a small, insignificant tendency to elevate the plasma digoxin level. Nitrendipine co-administration (10 and 20 mg once daily) did not significantly alter systolic time intervals, as non-invasively measured haemodynamic parameters, compared to digoxin treatment alone. Thus, nitrendipine 20 mg daily caused a significant increase in plasma digoxin concentrations and in its AUC, which would rarely be of clinical relevance.

Adult↗
PubMed1986

Quantitative study of cell interaction with collagen and fibronectin.

The interaction of BHK-fibroblasts with collagen or fibronectin-collagen complex was investigated quantitatively. For that purpose an improved method for production of defined cell substrata was developed. The method permitted reproducible coupling of different ligands to glass via an amino or carboxyl group. BHK-cells grown on collagen required a minimum density of 15-20 ng collagen/cm2 for spreading. When grown on fibronectin adsorbed on collagen the cells were found to remove fibronectin from the substratum at a rate of 0.15 pg/(cell X h).

Animals↗
PubMed1985

[High-dose cytarabine treatment: a promising therapy modality in acute resistant myeloid leukemias in recurrence].

High dose Cytarabin in relapsed and refractory acute leukaemia. High dose cytarabin can be very effective for the treatment of acute leukaemia resistent to conventional cytarabin doses. Therefore 10 patients (6 males, 4 females) with ages ranging from 18 to 58 years (median: 34 years) refractory to conventional induction therapy were treated with 1 hour infusions of high dose cytarabin (3 g/m2 q 12 h for 6 days) 2 patients got additional 20 mg/m2 doxorubicin on days 7 to 9. According to this treatment, in 5 of the 10 patients complete remissions could be achieved. Without further treatment 3 patients relapsed after 4, 7 and 15 months leading to death in 2 or 3 months. 19 months after treatment 1 patient is in complete remission, though demonstrating meningosis leukaemica 5 months after high dose cytarabin. Another patient relapsed 14 months after high dose cytarabin, reaching another complete remission after treatment according to a ALL/AUL protocol [7]. 2 patients died in bone marrow aplasia and 2 patients did not show any response, dying 11 months after high dose cytarabin application. All patients demonstrated vomiting, nausea, diarrhea and allopecia. Bone marrow was profoundly depressed in all patients with severe granulocytopenia and thrombocytopenia for periods from 7 to 34 days. 3 to 5 days after the end of high dose cytarabin therapy 3 patients developed acute ceratitis and 2 patients conjunctivitis. 3 patients showed erythrodermia of their skin with epidermolysis in 2 of these patients.

Adolescent↗
PubMed1979

[Thorotrastosis and thorotrast carcinoma of the kidney. A differential diagnostic problem].

Thorotrast deposts produce intense fibrosis and it is not uncommon for malignant tumors to arise in such cases. Thus for example, renal carcinoma was observed 35 years after administration of Thorotrast. Such carcinomas may be difficult to diagnose in time because of radiogenic nephritis. In the light of experience with a 55-year old man, the reason for delayed carcinoma diagnosis was lack of formation of tumor nodes due to intense fibrosis resulting in diffuse and canalicular tumor spread. Hence it is obvious that angiography may not be diagnostic in such cases.

Contrast Media↗