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Biomedical subjects

A Hellstern

Publications and source records attributed to A Hellstern.

31 records · Page 2Linked to original sources
PubMed1989

[Oral and direct lysis of gallbladder calculi. Competing or complementary procedures to shockwave lithotripsy?].

Non-surgical treatment of cholesterol gallstones is possible with oral chemolitholysis employing chenodeoxycholic acid (CDA) and/or ursodeoxycholic acid (UDA), oral chemolitholysis following ESWL and direct dissolution with methyl tert-butyl ether (MTBE). Oral chemolitholysis takes a long time (6-24 months), is suitable only for small stones (up to 1.5 cm) and has a success rate of 60-70%. Prior ESWL shortens the duration of oral treatment moderately and can be employed with larger (up to 3 cm) stones; it is, however, quite expensive. The new method of direct chemolysis of gallstones is rapid, very cheap, and effective (approx. 95% success rate), but is an invasive procedure. If previous results obtained with MTBE are confirmed, it could become a therapeutic alternative to cholecystectomy in the case of very large and multiple stones.

Administration, Oral↗
PubMed1989

Ursodeoxycholic acid in primary biliary cirrhosis: results of a controlled double-blind trial.

We studied the effect of ursodeoxycholic acid on 18 women and 2 men with primary biliary cirrhosis, mainly stages I and II. After a 3-mo observation period, patients were randomized to a 9-mo treatment period with ursodeoxycholic acid, 10 mg/kg.day, or placebo. Two patients on placebo left the study. In all patients on ursodeoxycholic acid, mean values of serum glutamate dehydrogenase, aspartate and alanine aminotransferases, alkaline phosphatase, and gamma-glutamyl transpeptidase fell significantly by 48%-79% after 18-24 wk; 7 of 10 showed a mean decrease of 35% in immunoglobulin M after 24 wk. Prothrombin time, serum bilirubin, albumin, the antipyrin breath test, and plasma disappearance of indocyanine green were normal initially and did not change. Total serum bile acid concentrations increased; ursodeoxycholic acid became the predominant bile acid. No significant improvement occurred in the placebo group. Hepatic histology improved in 6 patients of the ursodeoxycholic acid group but deteriorated in 4 patients receiving placebo. In studies with erythrocyte membranes, changes in electron spin resonance revealed that ursodeoxycholic acid was less toxic than chenodeoxycholic or deoxycholic acid, and coaddition of ursodeoxycholic acid prevented their toxic effect.

Deoxycholic Acid↗
PubMed1988

[Percutaneous transhepatic lysis of gallstones using methyl tert-butyl ether. Report on 15 patients].

In 15 patients (13 women and two men) with cholesterol stones in the gall-bladder a special (Thistle) catheter was introduced into the gall-bladder under local anaesthesia by percutaneous transhepatic puncture. Methyl-tert-butyl ether, 2-15 ml, was injected via the catheter and removed again after 2 min. The number of stones per gall-bladder averaged 6.3 (1-20), size of stones 1.7 cm (0.5-2.8 cm), and duration of treatment 11.9 h (5-24 h). The stones dissolved in 13 patients (87%). In three patients stone débris remained: in one it was ultimately sucked out after reduction of the amount of débris with an EDTA-containing solution. The side effects of treatment--nausea and vomiting--were minor. In one patient there was a leak of bile from the gall-bladder after the procedure; a cholecystectomy was uneventfully performed. Another patient developed haemobilia which responded to conservative treatment. MTBE treatment has thus proved to be a successful and cheap method, low in side effects, in the treatment of patients with gall-stones.

Adult↗
PubMed1988

Dissolution of gall stones with an ursodeoxycholic acid menthol preparation: a controlled prospective double blind trial.

In a controlled prospective double blind trial patients with cholesterol gall bladder stones are treated with ursodeoxy-cholic acid (group A: UDCA 11.1 mg/kg per day; n = 16) and Ursomenth respectively (group B: a mixture of UDCA/menthol: 4.75 mg/kg per day each; n = 17). With same stone number and size (10-12 mm) there is a complete dissolution rate in group A of 38%, and of 53% in group B within 15-16.9 months. The response rate (complete + partial dissolution) amounted to 75% and 76% respectively. In group A there is one case of stone calcification, in group B none. Both preparations are free of unwanted effects. This suggests that the cyclic monoterpene menthol enhances the effect of UDCA and is of comparable effect to a mixture of six different terpenes used in former times.

Adult↗
PubMed1988

Endoscopy of the gallbladder as control of gallstone therapy with methyl-tert-butyl ether.

We report on a 36-yr-old woman with six gallstones measuring 2.1 cm each. Within 21 h of methyl-tert-butyl ether (MTBE) treatment, the stones had dissolved to a small amount of residue. As could be seen from cholesterol concentrations of samples of aspirated gallbladder bile and MTBE fractions, the dissolution process was slow to begin with, and gained momentum during hours 6-11, after which it decelerated. We discontinued treatment after 20 h, since the stone residue showed no change. Cholecystoscopy performed with an Edwards angioscope via a catheter showed that there were no stone remnants, but that there were flat polyps on the gallbladder wall. One hour later, we stopped the therapy. Cholecystoscopy is a useful method of assessing the results of MTBE treatment.

Adult↗
PubMed1987

Absolute bioavailability of metoclopramide given orally or by enema in patients with normal liver function or with cirrhosis of the liver.

Single dose studies were performed with three different dosage forms of metoclopramide (0.25 mg/kg body weight) in patients with normal liver function (i.v. (Paspertin): n = 4, oral liquid preparation: n = 4, rectal micro-enema n = 4) and patients with histologically confirmed cirrhosis of the liver (i.v.: n = 6, oral liquid preparation n = 4, rectal micro-enema: n = 8). Drug plasma-concentrations were measured over 8 h by a specific gas chromatographic method. The median areas under the plasma concentration-time curves (AUC0-8) after i.v. and rectal administration were similar in both groups. In contrast, the median oral bioavailability was considerably higher in patients with cirrhosis of the liver (82%) than in patients with normal liver function (60%). It can be concluded from this study, that dosage adjustments may be necessary in oral treatment of patients with cirrhosis of the liver, especially if prolonged therapy is required.

Administration, Oral↗
PubMed1985

Improved benefit/risk ratio of higher-dose metoclopramide therapy during cisplatin-induced emesis.

Metoclopramide (Paspertin) was infused intravenously in the high doses of 1.75, 3.5, 7.0, and 14 mg/kg body wt. per treatment cycle as antiemetic therapy for cisplatin-induced emesis (363 cycles, 25-120 mg/m2). The antiemetic potency of metoclopramide increased in a log linear manner, giving from 40% to 95% protection against emesis. Gastrointestinal motility showed a similar increase, i.e. diarrhoea. In contrast, the extrapyramidal reactions, namely akathisia, rigidity and acute dystonia, did not show a dose-dependent increase in frequency and remained constant over the dose range of 3.5-14 mg/kg per cycle. The results suggest increasing benefit of metoclopramide treatment with increasing doses of the drug.

Basal Ganglia Diseases↗
PubMed1985

Metoclopramide kinetics at high-dose infusion rates for prevention of cisplatin-induced emesis.

Eleven male subjects aged 24 to 58 yr received cisplatin, 90 to 120 mg/m2 iv, in combination with other cytostatic drugs such as doxorubicin HCl and bleomycin. To prevent emesis, two high-dose metoclopramide regimens were started 2 hr before cytostatic therapy. Regimen A (n = 7) consisted of a loading dose infusion of 1 mg/kg/hr over 2 hr, followed by a maintenance infusion of 0.5 mg/kg/hr over 24 hr (total dose was 14 mg/kg in each cytostatic cycle). Regimen B (n = 6) consisted of half the metoclopramide dose. The following kinetics were derived from the metoclopramide steady-state plasma levels and the t1/2 of the elimination phase 26 to 38 hr after dosing (median value and range are listed): Steady-state plasma concentration in group A and group B was 750 (480 to 1520) and 360 (300 to 480) ng/ml plasma. Drug clearance in group A and group B was 0.67 (0.3 to 1.0) and 0.70 (0.5 to 0.8) l/hr/kg. Volumes of drug distribution in group A and group B were 4.4 (1.9 to 6.5) and 4.3 (3.2 to 5.9) l/kg. Values for the t1/2 in the elimination phase in group A and group B were 4.7 (3.0 to 5.4) and 4.3 (3.7 to 5.1) hr. It appears that metoclopramide kinetics at high doses were dose linear, i.e., without evidence of cumulation. There were few side effects; vomiting was effectively suppressed by both regimens.

Adult↗
PubMed1982

Sex differences in rat liver bile acids.

Male Wistar rats show higher relative liver weights and higher weights of mitochondrial and microsomal fractions than females. Their relation of subcellular fraction weights tends more to the microsomal side. In liver homogenate and subcellular compartments, males contain significantly higher concentrations of beta-muricholic acid and other metabolites of chenodeoxycholic acid, females higher proportions of chenodeoxycholic acid. Higher concentrations of potentially toxic nonsulphated dihydroxy bile acids in the liver of female rats could be a sign of slower elimination, and the cause of higher susceptibility of females to liver injury induced by bile acid administration.

Animals↗
PubMed1978

[The influence of chenodeoxycholic acid on the concentrations of nonsulfated bile acids in the small and large intestinal mucosa of rats (author's transl)].

In male Wistar rats nonsulfated bile acids of small and large intestinal wall and feces are analysed after 2, 5, 9 and 14 days of oral administration of 20 or 90 mg chenodeoxycholic acid (CDCA)/kg. Development of body, intestinal, and fecal weights is assessed. A transient reduction of daily body weight gain and small and large intestinal weights is compensated after 14 days. Fecal weights are above controls under 20 mg/kg, below controls under 90 mg/kg. Containing about 2 mg, i.e. nearly 4% of the bile acid pool, the intestinal wall holds four times more bile acids than the liver. Under CDCA administration bile acid concentrations in the small intestinal wall and feces rise, and remain almost unchanged in the colonic wall. Changes after CDCA administration suggest that bile acid absorption is accompanied by an increase in mucosal bile concentration. In the colonic wall the increase in bile acid concentration after CDCA administration correlates with the passive permeability coefficient.

Animals↗
PubMedDate not supplied

Plasma levels and urinary excretion of lormetazepam in patients with liver cirrhosis and in healthy volunteers.

Plasma levels and urinary excretion of lormetazepam (Noctamid-ampoules; 2 mg/10 ml) were studied after i.v. (0.015 mg/kg b.w.) and after p.o (0.03 mg/kg b.w.) administration of the drug to five patients with cirrhosis of the liver (C) and to five young male volunteers (N). The cirrhotic patients exhibited higher drug plasma levels (Cmax p.o.: 11-43 ng/ml [C] vs. 11-16 ng/ml [N]) and higher AUC0-24 values of the unchanged drug (i.v.: 66-102 ng.h/ml [C] vs. 54-72 ng.h/ml [N]; p.o.: 83-188 ng.h/ml [C] vs. 74-113 ng.h/ml [N]). The absolute bioavailability was increased in the C-group with 57-134% vs. 52-84% [N]. The total plasma clearance of lormetazepam was 3 ml/min/kg in the C-group and 4 ml/min/kg in the N-group and thus within the range known for elderly and young male subjects. Conversely to the parent compound, the AUC-figures of its 3-OH-glucuronide were higher in the N-group (346-434 ng.h/ml) than in the C-group (149-371 ng.h/ml). In 24 h pooled urine samples of both groups, the glucuronide of lorazepam, the N-demethylated metabolite, accounted for approximately 5-14% of the dose fraction excreted as lormetazepam glucuronide. Apart from increased levels of the unchanged drug due to porto-systemic shunt and/or disease-dependent lower glucuronidation rate, the pharmacokinetics of lormetazepam were not altered in cirrhotic patients. It can therefore be concluded that for this group of patients the drug can be administered according to the same dose regimen as that used for normal subjects.

Administration, Oral↗