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Biomedical subjects

M Wenk

Publications and source records attributed to M Wenk.

At least 55 records · Page 3Linked to original sources
PubMed1982

[Netilmicin in refractory urinary tract infections. Good therapeutic effect in spite of long dosage intervals].

Aminoglycoside antibiotics are useful--despite potential toxicity--for treating urinary tract infection when other antibacterial agents have failed to eradicate bacteriuria. That this is true of the recently introduced aminoglycoside netilmicin was shown by 16 cases of tenacious and frequently recurring urinary tract infection. In contrast to previous recommendations, but relying on well known pharmacokinetic data which show prolonged urinary excretion of aminoglycosides, netilmicin was administered according to the following dosage schedule: Intramuscular injections of 3 mg/kg in cases where renal function was unimpaired, and of 2 mg/kg where it was reduced, were administered at dosage intervals of 1 to 4 days. Peak serum levels of netilmicin measured 1 hour after intramuscular injection were within the expected range of 8-14 micrograms/ml (3 mg/kg) and 6-10 micrograms/ml (2 mg/kg). As a result of the long dosage intervals the serum trough levels were usually far below 1 microgram/ml except in patients with moderate renal failure. Urinary concentrations of netilmicin, however, remained for the most part above the limit of antibacterial activity throughout the dosage intervals of 1 to 4 days. One week after the usual three weeks treatment course, urinary concentrations were still between 1 and 5 mcg/ml, and slowly decreasing amounts of the drug could be detected at least in traces up to 3 months beyond the last dose. Considering the type of urinary tract infections selected to receive netilmicin, the response to treatment was satisfactory and seemed unaffected by the long dosage intervals. Bacteriological cure was achieved in 5 of 11 infections associated with chronic pyelonephritis or analgesic nephropathy and in 4 of 5 urinary infections in patients with renal transplants. Treatment failures could be accounted for by obstructive lesions, stones, and in one transplanted patient by infection localized to her own shrunken kidneys. No instance of ototoxicity or nephrotoxicity due to netilmicin could be detected. Netilmicin administered according to the dosage schedule described can be recommended for ambulatory treatment of tenacious, recurring urinary tract infections due to gram-negative bacteria and refractory to cure by the usual oral antibiotic therapy.

Drug Administration Schedule↗
PubMed1982

[Slower lidocaine elimination and dose adjustment in patients with heart failure].

In 21 patients with acute coronary artery disease the influence of cardiac failure on the elimination of lidocaine (L) was evaluated by repeated serum level measurements during and after a therapeutic L-infusion. Lidocaine clearance (Cl) was less than 8 ml/min/kg in 9 of 13 cases with congestive heart failure (CHF), while in 7 out of 8 patients without CHF Cl-values were 8-12 ml/min/kg. Due to wide interindividual variability in the CHF group, however, mean values were not significantly different: 7.3 +/- 2.9 vs. 9.52 +/- 1.54 ml/min/kg (p greater than 0.05). In 3 patients receiving a simultaneous nitroglycerine infusion Cl was greater than 10 ml/min/kg despite clinical signs of CHF. The t 1/2 of L was significantly prolonged in patients with CHF: 4.29 +/- 2.14 vs. 2.43 +/- 0.58 h (p less than 0.05). It was not possible to determine individual L-dose requirements by bedside clinical examination alone. Serum level monitoring is therefore recommended in order to optimize L-therapy in patients with life-threatening arrhythmias, severe congestive heart failure and hypotension.

Arrhythmias, Cardiac↗
PubMed1982

Homogeneous enzyme immunoassay for netilmicin.

A newly developed homogeneous enzyme immunoassay for the determination of netilmicin in serum was evaluated and compared with a radioenzymatic assay. A total of 102 serum samples from patients treated with netilmicin were measured by both methods. This comparison showed an excellent correlation (r = 0.993). The enzyme immunoassay has proved to be precise, accurate, and specific. Because of its rapidity and the ease of performance, this method is a useful alternative to current assays for monitoring serum netilmicin concentrations.

Gentamicins↗
PubMed1982

Sensitivity to two-stage carcinogenesis of SENCAR mouse skin grafted to nude mice.

SENCAR mice are extremely susceptible to two-stage skin carcinogenesis, while BALB/c mice are relatively resistant. Skin grafts to BALB/c nude mice were performed with full-thickness skin from SENCAR and BALB/c donors, and tumor formation was monitored in grafted skin, surrounding host skin, and intact SENCAR, BALB/c and nude mice. Initiation was accomplished by exposure to 20 micrograms dimethylbenz(a)anthracene and promotion by repeated exposure to 12-O-tetradecanoylphorbol-13-acetate. SENCAR skin retained a high sensitivity to carcinogenesis when grafted to nude hosts, whereas BALB/c skin remained resistant. The donor type did not influence the tumor yield in surrounding nude host skin. The rate of tumor regression was not altered in SENCAR skin grafts on nude mice relative to intact SENCAR skin. These results indicate that the unusual sensitivity of SENCAR epidermis to chemical carcinogenesis is not due to altered systemic factors but is a property of the skin itself.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Gentamicin-induced acute renal failure in the rat. Effect of dehydration, DOCA-saline and furosemide.

Acute renal failure was induced in rats by subcutaneous injection of 200 mg/kg body weight gentamicin on 3 consecutive days. Following the last gentamicin injection, the animals began to produce increased amounts of dilute urine and usually remained polyuric throughout the experimental period which lasted up to 2 weeks. Plasma concentrations of creatinine rose to values between 2 and 10 mg%, of urea to values between 100 and 1,000 mg% 5-7 days after the last gentamicin injection and returned to levels slightly above control after 14 days. Average proximal tubular pressure was slightly elevated to 13.7 +/- 0.5 mm Hg on the 2nd day after the last gentamicin dose, decreased to 6.1 +/- 0.4 mm Hg after 1 week, and returned to 11.8 +/- 0.2 mm Hg after 2 weeks (control proximal tubular pressure 11.6 +/- 0.2 mm Hg). These average values hide the fact that early in this model of gentamicin-induced acute renal failure many tubules had proximal tubular pressures increased to values between 18 and 25 mm Hg, suggesting tubular obstruction. Decreased proximal tubular pressures and the histological finding of wide-spread necrosis of proximal convolutions is suggestive of tubular leakage. Dehydration, similarly to other models of acute renal failure, markedly potentiated gentamicin-induced acute renal failure. Salt diuresis induced either by DOCA-saline or by furosemide failed to afford functional protection and increased the degree of morphological damage. No relation was found between the concentration of gentamicin in renal tissue and the degree of functional or morphological impairment.

Acute Kidney Injury↗
PubMed1980

[Serum concentration measurements for the monitoring of anti-arrhythmic therapy with lidocaine].

Repeated measurements of lidocaine serum levels during antiarrhythmic treatment were performed by enzyme-immunoassay (EMIT) in 16 patients with acute myocardial infarction. In 12 cases the frequently employed standard dose (100 mg i.v. followed by infusion of 2 mg/min) was not sufficient to reach optimum lidocaine (2-5 mg/l) during the first 2 hours. In this period 6 patients had persistent ectopic beats and required additional bolus injections and increased infusion rates. Lidocaine elimination was delayed in patients with heart failure, which led to potentially toxic drug accumulation in 3 instances. This study indicates the need for individual adaptation of lidocaine dosage in patients with myocardial infarction, especially where left ventricular function is impaired. Monitoring of serum lidocaine levels by a rapid and reliable assay such as the EMIT system may greatly facilitate this task.

Adult↗
PubMed1980

Rapid prediction of steady-state serum theophylline concentration in patients treated with intravenous aminophylline.

In 15 acutely ill asthmatics the steady-state serum theophylline concentration was predicted by the method of Chiou et al. using two serum concentration measurements obtained 1 and 5 h after starting a continuous infusion of aminophylline. Two theophylline assays with different precision characteristics were compared. With a precise HPLC-assay the prediction was excellent: prediction error (predicted minus measured concentration) = -0.22 +/- 1.97 mg/l (mean +/- SD); r = 0.922. When the theophylline concentration was determined by a rapid enzyme immunoassay of lower precision, but convenient for clinical use, the prediction was less accurate (prediction error = 0.58 +/- 3.88, r = 0.852). However, it was still clearly superior to dosing recommendations based on the population average of theophylline clearance, even after taking into consideration the effect of smoking, congestive heart failure and cirrhosis (prediction error = 3.62 +/- 13.36, r = 0.560). As employed in this study, the method may be useful in helping the physician to choose the optimal dose in severely ill asthmatics.

Aminophylline↗
PubMed1980

[Comparison of methods of determination of serum doxycyline assessing relative bioavailability of two commercial formulations (author's transl)].

The present study was undertaken to evaluate the accuracy of the analytical results of an investigation of relative bioavailability of two doxycycline preparations. Six methods in four laboratories were applied: one fluorimetric, three high-pressure-liquid-chromatographic and three microbiological methods. The analyses were performed after coding the samples. In all cases the two preparations were bioequivalent. When comparing the methods, it could be shown that the fluorimetric method was slightly more accurate than the others. The HPLC-methods were almost as accurate. The results of the microbiological determinations showed the lowest accuracy. Two of the results were in good agreement with the biochemical methods, whereas the third showed such a high deviation that a comparison was no longer possible. Altogether a good agreement of all compared methods (except one) could be demonstrated.

Biological Assay↗
PubMed1979

[Delayed elimination of aminoglycoside antibiotics: importance for clinical use].

In 7 patients the elimination of amikacin (4), tobramycin (1) and gentamicin (2) in serum and urine was measured over several days after cessation of therapy. All three aminoglycosides showed multicompartmental pharmacokinetics with a terminal half life ranging between 46 and 150 hours. Using computer simulations, it is shown that slow drug accumulation in the body is to be expected during multiple dose therapy. Therefore, the indiscriminate use of these drugs should be avoided and the duration of therapy kept as short as possible.

Amikacin↗
PubMed1979

Multicompartment pharmacokinetics of netilmicin.

The pharmacokinetics of a single dose of netilmicin (NM) was studied in 6 healthy volunteers. Elimination of the drug was followed in serum and urine for 24 h and 72 h, respectively. NM concentrations were measured with a modified radioenzymatic assay. A three compartment open model was employed to calculate the pharmacokinetic parameters. Following the rapid initial distribution, biphasic elimination with half lives of 1.99 (t 1/2 beta) and 36.89 h (t 1/2 gamma) was demonstrated. Measurable amounts of NM were excreted in the urine for up to 72 h. The volume of distribution at steady-state (Vdss) of 0.68 l/kg was 3 to 4 times larger than previously reported for this antibiotic. NM plasma clearance was 91 ml/min and the renal clearance was 67 ml/min. The data indicate that on repetitive dosing the amount of drug in the body would be considerably underestimated if the prolonged terminal elimination phase were not taken into account. During prolonged treatment, accumulation of NM in renal and other tissues is likely to occur, as has been described for other aminoglycosides. The possible consequences of this pharmacokinetic behaviour are discussed.

Adult↗
PubMed1978

Experimental pancreatic carcinogenesis. II. Lifetime carcinogenesis studies in the outbred Syrian golden hamster with N-nitroso-bis(2-hydroxypropyl)amine.

A high incidence of pancreatic duct neoplasms was induced in outbred male Syrian golden hamsters following weekly sc injection of N-nitroso-bis(2-hydroxypropyl)amine for life. The first such tumors appeared as early as 16 experimental weeks; the maximum incidence reached 100% by the termination of the study. Tumors in the respiratory tracts and angiosarcomas of the livers of the hamsters were also observed in high frequency. Latency of the induced neoplasms was significantly decreased by the substitution of distilled water for olive oil as the vehicle for the carcinogen.

Animals↗
PubMed1977

[Determination of serum digoxin: a path to better control of therapy?].

The usefulness of serum digoxin measurements in the diagnosis of digitalis toxicity was studied prospectively in hospitalized patients. Serum levels were increased above 2 ng/ml in 28 of 32 cases with digoxin-induced arrhythmias and/or gastrointestinal symptoms, whereas only 1 of 35 non-toxic patients had an abnormal serum concentration. There was, however, no direct relationship between the type of toxic manifestation and absolute values of serum digoxin.

Arrhythmias, Cardiac↗