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Biomedical subjects

M Hanisch

Publications and source records attributed to M Hanisch.

At least 19 recordsLinked to original sources
PubMed2005

Common genetic variants in the interleukin-6 and chitotriosidase genes are associated with the risk for serious infection in children undergoing therapy for acute myeloid leukemia.

Infectious complications represent a substantial cause of morbidity and mortality in children undergoing therapy for acute myeloid leukemia (AML). Since it has been shown that alterations in innate immune pathways contribute to the risk for serious infections, we analyzed well-characterized variants in innate immune genes (TNF, IL6, IL8, MPO, CHIT, FCGR2A, TLR2, and TLR4) to determine their possible contribution to infectious complications during therapy for pediatric AML. The study population consisted of 168 North European Caucasian children enrolled on the clinical trial AML-BFM 93. We found an association between Gram-negative bacterial infection and common, functional variants in two genes, IL6 and CHIT. The risk for infection was significantly higher in children with the G allele in the IL6 promoter at -174 bp (P=0.026) and in patients with the H allele of CHIT (P=0.033). The promoter variant in IL6 has been shown to increase expression while the H allele disrupts both function and circulating levels. Our data suggest that variant alleles of both IL6 and CHIT could influence susceptibility to infection with Gram-negative bacteria in children undergoing therapy for AML. Follow-up studies, namely replication association studies and in vitro investigation of these common polymorphisms, are warranted to confirm these observations.

Acute Disease↗
PubMed1999

Influence of fentanyl, alfentanil, and sufentanil on motor evoked potentials.

The effects of the opioids fentanyl, alfentanil, and sufentanil on motor pathways were studied in a total of 30 rabbits. Compound muscle action potentials (CMAP) were recorded from the extensor muscles of the upper extremity as well as evoked spinal cord potentials (ESCP) from the thoracic epidural space in response to electrical stimulation of the motor cortex. After establishing stable baseline values, an equipotent intravenous bolus of one of the three opioids was applied that abolished reflex motor response to noxious stimulation. Motor evoked potentials (MEP) were recorded from the time of bolus administration until recovery of MEP amplitudes and latencies. Afterwards, the opioids were administered continuously with cumulative dosage up to total absence of motor evoked response. Our results show a dose-dependent suppression of the CMAP: When reflex movement to noxious stimulation was extinguished, we found a significant (P < .001) reduction of the amplitudes to 34+/-18% (mean +/- SD) in the fentanyl group, to 43+/-24% in the alfentanil group, and to 53+/-20% of baseline values in the sufentanil group. Increasing opioid plasma levels were associated with complete extinction of the CMAP. We hypothesize that the descending volleys within motor pathways are mainly inhibited at a spinal level, because ESCP, particularly the number of spinal I-waves, are not severely affected even when CMAP are completely suppressed. In conclusion, intraoperative monitoring of descending pathways by means of MEP during anesthesia with opioids is feasible at anesthetic plasma concentrations maintaining a surgical level of analgesia. Even with high opioid plasma levels, a valid MEP monitoring could be performed evaluating neural activity of spinal MEP.

Action Potentials↗
PubMed1998

Fluorometric determination of total retinyl esters in triglyceride-rich lipoproteins.

A time-consuming sample preparation and measuring procedure is required for the quantitation of retinyl palmitate by HPLC. We developed a fluorometric method for the determination of total retinyl esters in chylomicrons, chylomicron remnants, and VLDL. This method is precise, sensitive, rapid, simple, and particularly useful for large-scale studies of postprandial lipid metabolism. Because the turbidity of postprandial lipemic samples interferes with the fluorescence measurement, all samples were incubated for 10 min with a clearing buffer containing esterase and detergents. This buffer eliminates the turbidity and hydrolyzes all retinyl esters to retinol. The fluorescence signal (excitation wavelength, 330 nm; emission wavelength, 490 nm) was linear from 0.1 mg/L up to 4 mg/L retinyl palmitate, and the CVs were 3.6% within-run and 5.1% within-series. A first application studied postprandial lipoproteins, which were first separated by ultracentrifugation and then subjected to size exclusion chromatography. Fluorescence analysis revealed that the chylomicron density fraction contains large amounts of chylomicron remnants.

Buffers↗
PubMed1996

Clearance of postprandial lipoproteins in normolipemics: role of the apolipoprotein E phenotype.

The hepatic clearance of triglyceride-rich lipoproteins is mediated via apolipoprotein (apo) E which occurs in three common isoforms, apoE2, apoE3 and apoE4. To study the importance of the apoE isoforms on the response curves of different triglyceride-rich lipoproteins and the effect of chylomicron remnants on the composition of HDL, 37 normolipemics were investigated after a standardized fatty meal (8 apoE2/E2, 8 apoE2/E3, 8 apoE3/E3, 7 apoE3/E4 and 6 apoE4/E4). These individuals were matched for age, body mass index, fasting triglycerides, HDL-cholesterol, and apoA-I. A delayed chylomicron remnant clearance was observed only in apoE2 homozygotes, and this delay was neither correlated with fasting lip ds nor with peak lipoprotein concentrations. In apoE2/E3 heterozygotes, in contrast, the defective isoform E2 appears to be compensated for by the normal apoE isoform E3. In non-apo-E2/E2 individuals, the chylomicron remnant response was highly correlated with the magnitude of chylomicron and VLDL responses, with fasting triglycerides, and with the triglycerides enrichment and cholesterol depletion of HDL. These correlations were not observed in apoE2/E2. From these results we conclude that the chylomicron remnant response curve is an indicator of the extent of postprandial lipemia in non-apoE2/E2 individuals only.

Adult↗
PubMed1992

Fish oil treatment and apolipoprotein(a).

Two recent reports showed a lowering of elevated lipoprotein(a) levels upon treatment with fish oil. The aim of this paper was to confirm this finding and to establish a dose-effect relationship. A double blind, placebo controlled cross-over study was carried out in 48 subjects with apolipoprotein(a) ("Apo(a)") values between 34 and 1062 U/l (median 387 U/l). The subjects were divided into 3 groups receiving 3.5, 7.1 and 10.6 g omega-3 fatty acids/day during 28 days. Parameters measured were blood levels of eicosapentaenoic acid ("EPA"), Apo(a) and fasting blood lipids. EPA levels rose in the three dosage groups by factors 7, 9 and 14, respectively, if compared to values upon placebo. Triglycerides were significantly lowered in a dose depending manner. Apo(a), however, was not changed. This held true for different baseline Apo(a) values and different fish oil dosages. It is concluded that fish oil treatment during 4 weeks cannot lower elevated Apo(a) levels.

Adult↗
PubMed1988

[Fatty acid composition and degree of peroxidation in fish oil and cod liver oil preparations].

Omega-3-fatty acids are increasingly used by the selfmedicating patient. Since fish oils in capsules are regarded as dietary food, there are neither official regulations in the Federal Republic of Germany concerning a minimum content of omega-3-fatty acids nor detailed rules for the limitation of autoxidation of these highly reactive substances. Both fatty acid composition and the degree of lipid peroxidation were measured in this study in 23 OTC fish oil preparations. The proportion of omega-3-fatty acids was in most fish oils about 30%; exceptions were the only ethyl ester among the preparations with 59% and the cod liver oils (13% to 22%). Regarding the peroxide value considerable differences were found: the lowest was 2 and the highest was 44.7. Since lipid peroxides and their degradation products are basically toxic, a limitation of the allowed degree of lipid peroxidation in fish oils is strongly recommended.

Animals↗
PubMed1985

Effects of haemodialysis on the pharmacokinetics of muzolimine.

UNLABELLED: High ceiling diuretics allow a better control of fluid balance in dialysis patients with a minimum urine flow of 500 ml/day. The pharmacokinetics of the high ceiling, long acting diuretic muzolimine (M) was investigated in 6 patients on regular dialysis therapy. METHODS: Concentrations of unchanged M in plasma were determined by high performance thin-layer chromatography (HPTLC) after a single oral dose of 240 mg up to 26 h: A) during and after the performance of dialysis lasting for 3 h, B) 20 h after finishing haemodialysis therapy (non-blind randomized cross-over study). RESULTS: The M plasma levels and the M half-lives did not differ between the two treatment groups (half-life A: 5.1 +/- 0.24 h; B: 4.8 +/- 0.51 h). The M peak concentrations were between 2 and 5 micrograms/ml and were reached 2 h post administration or even earlier. The mean M plasma levels 24 h after administration were in the same range (A: 0.33 +/- 0.16 microgram/ml; B: 0.33 +/- 0.11 microgram/ml).

Adult↗
PubMed1985

Effects of muzolimine and of a combination of hydrochlorothiazide/triamterene in healthy subjects and in nephrotic patients.

The diuretic effects of 30 mg muzolimine and 25 mg hydrochlorothiazide/50 mg triamterene were comparable in healthy subjects and nephrotic patients (serum albumin less than 32 g/l, creatinine clearance greater than 50 ml/min/1.73 m2). A single daily dose of 30 mg muzolimine or 25 mg hydrochlorothiazide/50 mg triamterene was sufficient in the majority of the investigated nephrotic patients. The different diuretic effects which were observed in nephrotic patients were not related to the severity of hypalbuminemia, but rather to differences in preceding diuretic treatment. Plasma levels and urinary excretion of unchanged muzolimine were comparable in healthy subjects and nephrotic patients after one day of diuretic treatment; after seven days of treatment plasma levels of muzolimine were significantly lower and urinary excretion significantly higher in nephrotic patients than in control subjects.

Adolescent↗
PubMed1985

Pharmacodynamic and pharmacokinetic correlation of muzolimine with and without aluminium hydroxide.

The objective of the reported study was to investigate whether aluminium hydroxide administered in addition to muzolimine interferes with the pharmacodynamics or the pharmacokinetics of the drug. For this purpose a cross-over study in 6 healthy male volunteers was carried out in which each subject received muzolimine and after a wash-out period muzolimine together with Aludrox. To avoid interferences of a psychological nature a third period with placebo was added. The administrations were randomised. The excreted urinary volume was measured, and blood was taken at relevant times in order to follow the pharmacokinetic profile. These are the results: Urinary excretion after the oral administration of muzolimine was within normal limits compared with the literature. There was no change in elimination with respect to either extent or time characteristics after the combined administration of Aludrox. There was no change in the pharmacokinetic profile either.

Aluminum Hydroxide↗
PubMed1985

Food and muzolimine interaction.

The influence of food on the bioavailability of muzolimine was investigated in a non-controlled cross-over study. Six healthy volunteers received 40 mg muzolimine directly after a standardized American breakfast (non-fasting volunteers) and, one week later, after an overnight fast with breakfast 90 min after drug intake (fasting volunteers). The concentrations of muzolimine in plasma and urine were determined between 0 and 48 h after administration. Results (means +/- SEM): in the fasting volunteers, the areas under the muzolimine plasma level curves (0-32 h) were higher than in the non-fasting volunteers (3002 +/- 390 vs. 2038 +/- 344 ng X h/ml, p less than 0.001), the peak concentrations were higher (332 +/- 36 vs. 176 +/- 38 ng/ml, p less than 0.05) and appeared earlier (1.8 +/- 0.2 h vs. 4.0 +/- 0.5 h, p less than 0.01). Also, the urinary volumes and sodium excretion were higher in the fasting volunteers than in the non-fasting volunteers. Hence, the bioavailability of muzolimine is reduced if administered after a meal which should be considered in the treatment schedule.

Adult↗
PubMed1985

Pharmacokinetics of muzolimine after oral administration with and without aluminium hydroxide in healthy volunteers.

The pharmacokinetics of muzolimine administered with and without aluminium hydroxide was investigated in volunteers (randomized non-blind cross-over study). Six healthy male volunteers aged 20 to 28 years with a mean body weight of 68 +/- 8 kg received 40 mg muzolimine after a standardized breakfast without and with 1760 mg aluminium hydroxide (Aludrox) administered 10 min before breakfast. Muzolimine concentrations were determined in plasma and urine between 0.5 and 48 h post dosing. The data were analysed using a two- or three-compartment open model. The pharmacokinetic parameters of muzolimine, e.g. absorption half-life, peak concentration, time to reach peak concentration, AUC and mean time, obtained with both treatment regimens, did not show any significant difference (analysis of variance). As a conclusion, the pharmacokinetics of muzolimine is not altered by the ingestion of aluminium hydroxide, which might be important for patients with advanced renal failure.

Adult↗
PubMed1985

Muzolimine as monotherapy in the treatment of patients with congestive cardiac failure.

The efficacy of muzolimine (BAY g 2821) in doses of 30 or 60 mg/day was studied over an observation period of 4 weeks in 48 patients with mild to moderate heart failure (NYHA stage 2 or 3) in a biometrically planned, multicentre study. Eleven of these patients were excluded from the evaluation of efficacy for various reasons. All 37 patients who remained (23 men and 14 women; mean age 59.6 years, mean body weight 73.8 kg) were treated throughout with one tablet per day (30 mg). A marked improvement of the symptoms of cardiac insufficiency was observed in these 37 evaluated cases in the course of the treatment period. At the end of the study body weight was reduced by 1.8 kg, heart rate fell from 84 to 75 beats/min and blood pressure decreased from 154/88 to 145/85 mm Hg on average. The laboratory parameters tested failed to show any clinically abnormal alterations. Twelve of 48 patients complained of side effects (dizziness, headaches, vomiting, nausea), these developing largely in the first 2 weeks and being transient in character. To summarize, it can be stated that patients with chronic heart failure (NYHA 2 and 3) can be effectively treated by muzolimine monotherapy.

Blood Pressure↗