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Biomedical subjects

W Kirch

Publications and source records attributed to W Kirch.

At least 289 records · Page 16Linked to original sources
PubMed1977

Macroamylasaemia after treatment with hydroxyethyl starch.

After infusion of 500 ml of 6% hydroxyethyl starch into fifty-four patients an increase of serum amylase was observed which in fifty-one cases exceeded the upper limit of normal (190 U/l). In most cases serum amylase reached twice the basal value. Renal function influenced the duration of the increase in serum amylase, but not the maximum increase (201+/-15 U/l; mean+/-SEM). In patients with advanced renal failure (glomerular filtration rate (GFR) = 2-10 ml/min) serum amylase was still markedly elevated after 72 h (298+/-24 U/l; mean+/-SEM). In patients with normal renal function (GFR greater than 90 ml/min) serum amylase decreased to 183+/-40 U/l (mean+/-SEM) within 72 h without reaching basal values. After infusion of HES no changes were observed in serum lipase or in amylase or lipase activities in duodenal secretion. Amylase excretion in the urine decreased. The assumption of a macroamylasaemia caused by formation of an HES-amylase complex was confirmed by gel filtration. The elimination from plasma of this high molecular enzyme-substrate complex is slow and causes hyperamylasaemia. In no case was the macroamylasaemia associated with signs or symptoms. An awareness of this causal relationship seems to be important, to avoid the erroneous diagnosis of a pancreatic disease.

Adult↗
PubMed1977

Hydroxyethyl starch-induced macroamylasemia.

Summarizing, the following results were obtained: 1. After infusion of 500 ml hydroxyethyl starch 6% in all patients an increase of serum amylase occurred, which in most cases reached values twice as high as the basal value. 2. This hyperamylasemia is caused by the formation of a high molecular HES-amylase complex, which cannot be easily eliminated. 3. In no case was hyperamylasemia associated with other clinical signs or symptoms.

Amylases↗
PubMed1977

[Formation of high-molecular aggregates between serum amylase and colloidal plasma substitutes (author's transl)].

The distribution of molecular weights of human serum amylase was studied by gel filtration of serum, obtained before and after infusion of the colloidal plasma substitutes hydroxyethyl starch, dextran and gelatin, respectively. Both in serum, drawn after intravenous infusion of hydroxyethyl starch, and in a solution of hydroxyethyl starch with serum we observed a significant increase in the molecular weight of serum amylase. The occurrence of this "macroamylase" may be explained by the formation of aggregates between hydroxyethyl starch and amylase. Because of its high molecular weight the elimination of this, presumably, enzyme-substrate-complex is retarded, thus leading to the observed increase of serum amylase activity. In contrast to these observations concerning hydroxyethyl starch no change in the apparent molecular weight of serum amylase was observed following the infusion of either gelatin or dextran or their solutions with serum.

Amylases↗
PubMed1975

[Dosage and elimination of Dextran 40 in patients on hemodialysis (author's transl)].

In 24 patients on regular hemodialysis the serum levels and the half-life of dextran 40 were determined after single or repeated infusion of dextran 40 (Rheomacrodex¿). One group of hemodialysis trainees had a dextran 40 half-life of 2237 +/- 447 min. In contrast, a second group, consisting of hospital dialysis patients, had a dextran 40 half-life of 4283 +/- 510 min, whereas patients with normal renal function had a half-life of 573 +/- 183 min. The difference in dextran half-life between the two groups of hemodialysis patients may be explained by the better residual renal function of our hemodialysis trainees. During hemodialysis no change in serum dextran levels could be observed. Intermitten hemodialysis, also, had no influence on the exponential elimination of dextran over a period of 6.25 days. Since hemodialysis by itself has no effect upon dextran elimination, the dosage fo dextran 40 has to be adjucted to the prolonged elimination time only, disregarding dialysis. After the fourth infusion of 50 g dextran 40 (twice a week 500 ml of 10% dextran 40) serum dextran levels exceeding 50 g/l and cutaneous bleeding were observed. To avoid these complications an initial saturation dose is suggested, followed by a maintenance dose adjusted to the impaired renal function.

Arteriovenous Shunt, Surgical↗
PubMed1975

[Fluoride content of teeth following treatment with Zircate paste].

We extracted the four lower incisive teeth 41, 42 and 31, 32 of ten patients in age of 50-73 years. The indication was a profound marginal parodontopathy. Before extraction the incisors of the right side were treated with 9% stannous-fluoride. Five minutes after treatment they and the unfluoridated left incisive teeth 31, 32 were extracted. For transformation of 19F to radioactive 20F the extracted teeth were exposed to neutrons in the nuclear reactor. The incorporated radioactivity was proportional to the fluoride-concentration. Considering fluoridated (128,45 +/- 13,659 mug/g) and unfluoridated (128,6 +/- 14,88 mug/g) teeth, the fluoride concentration did not differ significantly.

Aged↗
PubMedDate not supplied

Influence of inflammatory disease on the clinical pharmacokinetics of atenolol and metoprolol.

The influence of inflammatory disease on the pharmacokinetics of atenolol and metoprolol was investigated after administering single oral 100 mg doses of the drugs to six subjects. Each subject had a respiratory tract infection with an erythrocyte sedimentation rate (ESR) of over 20 mm in the first hour and a body temperature of at least 38.5 degrees. Since the subjects subsequently received atenolol and metoprolol when they were healthy, each person acted as his own control. Inflammatory disease had no influence on the kinetics of metoprolol. In contrast, mean peak plasma levels and AUC for atenolol were significantly lower, both by about 40 per cent, during infectious disease compared to the healthy state (p less than 0.05), where as renal clearance of atenolol slightly increased from 110.8 +/- 14.7 ml min-1 in the healthy state to 128 +/- 21.6 ml min-1, when the ESR's were elevated. The elimination half-life of atenolol, about 10 h, was not affected by the health status of the subjects. Reduced absorption in the gastro-intestinal tract and enhanced elimination of atenolol from plasma might account for the decreased AUC and peak plasma levels of the drug during inflammatory disease.

Adult↗
PubMedDate not supplied

Pattern of prescriptions issued by nursing home-based physicians versus office-based physicians for frail elderly patients in German nursing homes.

PURPOSE: The purpose of this study was to describe the physician prescription pattern for frail elderly patients in German nursing homes and to identify differences, if any, between that of physicians based in the nursing homes (A) and those with office-based practices (B). METHODS: Retrospective, longitudinal study of medication prescriptions on the basis of the database of a health insurance (Betriebskrankenkasse) in Berlin, Germany. We assessed the medication prescriptions for all 996 unselected insured individuals aged > or = 60 years who were insured throughout 1999 and lived in nursing homes. We analyzed selected patient characteristics and prescription data. Drugs were classified according to the WHO ATC code and were assigned a mean daily defined dose (DDD). RESULTS: 816 individuals were women and 180 were men. A total of 78% of women and 43% of men were aged 80 years or older. Two hundred sixty three patients were seen by nursing home-based physicians (A) and 733 by office-based physicians (B). The median of prescriptions per patient and year was 31 (A) and 37 (B) (p between groups < 0.001). Patients in Group A also received a lower number of DDDs in comparison to Group B (1109 vs 1250; p < 0.01). Costs were substantially higher in group B, and in both groups higher in the 60-69 years old in comparison to the more senior patients. The prescription pattern suggested a considerable frequency of inappropriate drug use in both groups in the following classes: psychopharmacological agents (neuroleptics, antidepressants, hypnotics), pain medication, digitalis glycosides, laxants and loop diuretics. On an average, office-based physicians (B) prescribed relatively more medications in all major classes with the exception of non-opiate analgesics, laxants and anxiolytics. CONCLUSIONS: These data are indicative of a considerable use of inappropriate medication for frail geriatric patients. Differences between the prescribing pattern among nursing home-based and office-based physicians were not substantial, however, the latter group prescribed relatively more drugs.

Aged↗
PubMedDate not supplied

Digitoxin and its metabolites in patients with liver cirrhosis.

Pharmacokinetic profile and urinary excretion of digitoxin and 4 metabolites were investigated in 9 patients with biopsy confirmed liver cirrhosis (median antipyrine clearance 20.0 +/- 5.4 ml/min; X +/- SEM) and were compared with that of 8 healthy volunteers (antipyrine clearance 36.9 +/- 4.9 ml/min) following intravenous and p.o. administration of 1 mg digitoxin. The kinetic parameters derived from the digotoxin plasma concentration time curve and from urinary recovery including total clearance of unchanged digitoxin did not differ significantly between both groups investigated. Renal clearance of digitoxin was 0.017 +/- 0.005 ml/min/kg in the patient group and 0.011 +/- 0.002 ml/min/kg in the volunteers (NS); it was 0.00340 +/- 0.00047 ml/min/kg and 0.00223 +/- 0.00039 ml/min/kg, respectively for digitoxigenin-bis-digitoxoside (NS), 0.00006 +/- 0.00001 ml/min/kg and 0.00016 +/- 0.00005 ml/min/kg for digitoxigenin-mono-digitoxoside (P < 0.05), 0.00041 +/- 0.00013 ml/min/kg and 0.00088 +/- 0.00032 ml/min/kg for digitoxigenin (P < 0.05), 0.00135 +/- 0.00049 ml/min/kg and 0.00113 +/- 0.00042 ml/min/kg for digoxin (NS). In conclusion, hydrolysis of digitoxin is altered in liver cirrhosis, whereby a significant reduction in the renal clearance and urinary recovery of digitoxigenin-mono-digitoxoside and digitoxigenin was seen in the present study.

Adult↗
PubMedDate not supplied

Bunazosin in patients with impaired hepatic or renal function.

Following a single oral dose of 6 mg bunazosin, a novel alpha 1-adrenoceptor antagonist, the pharmacokinetics and blood pressure behaviour of 37 patients were studied. 12 subjects had normal renal and hepatic function (mean creatinine clearance (GFR) 107 +/- 240 ml/min, antipyrine clearance (AP Cl) 47 +/- 10.2 ml/min; x +/- SD), 13 subjects had impaired renal function (mean GFR 38 +/- 11.5 ml/min, AP Cl 39 +/- 4.0 ml/min), and 12 patients had liver cirrhosis which was confirmed by liver biopsy (mean AP Cl 18 +/- 9.2 ml/min, GFR 92 +/- 8.1 ml/min). The groups studied were matched for age and body weight. The area under the plasma level time curve (AUC0-infinity) of bunazosin increased from 96.6 +/- 48.7 micrograms.ml-1.h in the normals to 157.0 +/- 101.0 micrograms.ml-1.h in the liver patients and to 298.2 +/- 199.4 micrograms.ml-1.h in patients with impaired renal function (P < 0.05). As there was a close correlation between plasma levels and antihypertensive activity of bunazosin in the present study, dosage adjustment of the alpha 1-receptor blocker in patients with impaired liver and kidney function appears to be mandatory.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Dose dependent tiracizine disposition in healthy volunteers: serum and urine kinetics and dose related ECG-changes.

The pharmacokinetics of tiracizine, a new class I antiarrhythmic agent, and 3 of its metabolites were assessed in serum and urine of 8 healthy extensive metabolisers after single oral administration of 50, 100, and 200 mg tiracizine hydrochloride. Additionally, tiracizine induced ECG-changes were compared between the different doses. With increasing doses enhancement of AUC and Cmax of tiracizine and its metabolites revealed a slight deviation from linearity indicated by exceeding the upper limits of the 95% nonparametric confidence interval set by 0.8-1.2 for the ratio (dose corrected parameters after the 100 and 200 mg dose, respectively)/(parameters after 50 mg). The increase of the dose corrected parameters after the 200 mg dose was about 1.3-fold compared with the 50 mg parameters for the parent compound as well as its metabolites. The significant decrease of the renal clearance of all 4 substances with increasing doses indicates that saturable tubular secretion mainly accounts for non-linearity. Due to the occurrence of non-linear (tubular secretion) as well as linear (glomerular filtration, hepatic metabolism) elimination in parallel, however, it is concluded that saturable tubular secretion is of minor importance at higher doses and should not be overestimated. However, there was some evidence for saturable hepatic tiracizine metabolism in 4 of the 8 participants. Therefore, a fall of apparent intrinsic clearance has also to be taken into consideration, especially at higher doses. PQ- and QRS-intervals were prolonged in a dose dependent manner and culminated at 1 h after drug intake. QTc-time, however, remained unchanged. A log-linear relationship between serum concentrations of the parent compound and PQ- as well as QRS-time is suspected for serum levels about 80 ng/ml, but has to be confirmed by individual pharmacokinetic-pharmacodynamic modelling. PQ- and QRS-intervals might be suitable for tiracizine therapeutic monitoring.

Adult↗
PubMedDate not supplied

Effect of cisapride and metoclopramide on digoxin bioavailability.

Pharmacokinetics of digoxin were investigated in six healthy volunteers following one week of digoxin monotherapy 0.25 mg b.i.d., and during coadministration of metoclopramide 10 mg t.i.d. or cisapride 10 mg t.i.d.. Metoclopramide reduced the peak plasma concentration of digoxin from 1.5 +/- 0.2 ng/ml to 1.1 +/- 0.1 ng/ml (mean +/- SEM) (p = 0.05), cisapride lowered the peak concentration to 1.3 +/- 0.1 ng/ml (p = 0.14). Metoclopramide prolonged the time required to reach the peak concentration of digoxin from 2 hr to 2.7 hr (p = 0.17), cisapride did not. Digoxin AUC0-12 (743 +/- 79 ng/ml.min) was reduced by 12% on coadministration of cisapride (653 +/- 38 ng/ml.min, p = 0.22) and by 19% on coadministration of metoclopramide (605 +/- 34 ng/ml.min, p = 0.06). It is concluded that the gastrointestinal absorption of digoxin is reduced by both substances. Monitoring of the patient's clinical status should be recommended when metoclopramide and cisapride are coadministered.

Adult↗
PubMedDate not supplied

Pharmacokinetics of guanfacine in patients undergoing haemodialysis.

Eight patients with terminal renal failure (GFR less than 5 ml/min) received guanfacine intravenously or orally at the beginning of a haemodialysis session lasting 5 hours. After intravenous administration the elimination rate constant of the unchanged drug was calculated to be 0.59 h-1, corresponding to an elimination half-life of about 12 h, which is similar to the values of patients with normal renal function. Following oral ingestion, only 2.4% of the guanfacine dose administered were extracted unchanged in the dialysate during the haemodialysis period. The clearance by dialysis was 53 ml/min for guanfacine, which represents about 15% of the total clearance of guanfacine reported in the literature. The low dialysis clearance of guanfacine is consistent with the high rate of biotransformation of the drug and its binding to red blood cells and plasma proteins. Thus guanfacine may be dosed independently of haemodialysis treatment periods.

Adult↗