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Biomedical subjects

P Müller

Publications and source records attributed to P Müller.

At least 343 records · Page 19Linked to original sources

On the glucose effect in acridine-induced frameshift mutagenesis in Escherichia coli.

Log-phase cells of E. coli growing in defined minimal media were washed, exposed to acridines in the same minimal salts solution, and plated to select for Nad+ revertants. At low mutagen concentration, treatment in the presence of the carbon source to which the cells were adapted resulted in a decrease in revertant yield of several orders of magnitude compared with the yield in the absence of a carbon source. At high mutagen concentration, however, a carbon source present during treatment caused a 2- to 150-fold increase in revertant yield (depending on the mutagen, the carbon source, and on the genetic background of the strain). In a strain lacking adenylate cyclase, acridine mutagenesis was not abolished under the experimental conditions used in this study, and the addition of cAMP during mutagenic treatment had no effect. In mismatch repair-deficient strains, the presence of glucose during treatment with low mutagen concentration did not cause a decrease in revertant yield as drastic as in the wild type. From the results reported here, we conclude that the glucose effect in acridine mutagenesis is due to an enhancement of mismatch repair.

Aminacrine↗

Human gastric acid secretion following repeated doses of AG-1749.

The effect of increasing doses (15 mg, 30 mg and 60 mg) of the substituted benzimidazole, AG-1749, on gastric acid secretion and fasting serum gastrin concentration has been studied after repeated administration to healthy volunteers. AG-1749 produced a dose-dependent and profound decrease in basal and stimulated gastric acid secretion in all volunteers, with almost total suppression at the highest dose. The extent of inhibition increased between Day 2 and Day 8 with the 15 and 30 mg doses of AG-1749. The inhibitory effect of AG-1749 appears to be fully reversible as control levels of acid output were reached 7 days after drug withdrawal. Seven days' dosing with 60 mg AG-1749 induced a more than threefold increment of fasting serum gastrin concentration, but this increase was still within the normal range. Seven days after cessation of dosing, fasting serum gastrin concentration returned to a pre-dose level.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Determination of AL01576 concentration in rat lenses and plasma by bioassay for aldose reductase activity measurements.

Investigations on the disposition of the highly effective aldose reductase inhibitor AL01576 were carried out in pigmented rats after oral dosing and topical administration of a 0.1% ophthalmic suspension by means of an assay modified from a previously described method measuring aldose reductase activity. The crude enzyme extract of pig lenses was used as a test system. From the activity remaining after addition of the plasma or lens extracts, the concentration could be determined since the inhibition constant (IC50) of AL01576 is known. With this procedure, the concentration of AL01576 in plasma and lenses of Brown-Norway rats given different doses of the drug for 42 consecutive days were determined and compared with a gas chromatographic assay technique. These data indicate that AL01576 is absorbed into the lens with a substantial portion redistributing into the lens following systemic delivery. Drug concentrations were correlated with efficacy measurements, though they were lower in an animal group treated with naphthalene to provoke cataract formation. In a second animal series with Brown-Norway rats over 5 days, AL01576 was administered three times per day to the right eye only. During the washout period, AL01576 had a long persistence in plasma and lenses following this short-term topical ocular administration.

Aldehyde Reductase↗

Percutaneous drainage of subphrenic abscesses.

Forty subphrenic abscesses were drained percutaneously in 37 patients. These abscesses were subsequent to abdominal surgery (28 patients), biliary obstruction and/or fistula (six patients), trauma (two patients) or acute pancreatitis (one patient). The procedures were usually monitored by duplex sonography and fluoroscopy (35 out of 40 cases), with an angled subcostal approach to the subphrenic space in over 85% of the cases. Forty-three drainage catheters were inserted using the Seldinger method; 37 (86%) had a size of 12 F or more, 21 were 16 F in size. Only two out of 43 catheters were double-lumen sump drains. The clinical condition improved after insertion of the catheter in all 37 patients. Definitive successful drainage, defined as hospital discharge without complementary surgery, was achieved in 32 patients (87%), without major complications. A temporizing effect was obtained in three additional patients (8%) who underwent curative surgery for the underlying process after complete drainage of the abscess. Two patients died from multiple organ failure before their abscess healed. Considerations for successful drainage of subphrenic abscesses include a good knowledge of the subphrenic space anatomy, the use of large-bore drainage catheters and the recognition and correct management of underlying enteric, biliary or pancreatic fistulas.

Adolescent↗

Sucralfate in the treatment of reflux esophagitis in adults: an update.

Sucralfate was evaluated in several clinical studies on reflux esophagitis, a total of over 400 patients were studied worldwide. In this study 49 patients with reflux esophagitis of stage I-III acc. to Savary and Miller were included. The evaluation was based on 41 patients, 22 received sucralfate suspension 1 g in 5 ml qid, 19 ranitidine 150 mg bid. The patients were treated for 8 weeks, endoscopic controls were performed before treatment and after 8 weeks. The healing rates were 64% in the sucralfate group and 68% in the ranitidine group and exhibited no significant difference (p greater than 0.05). Antacid consumption and symptomatic improvement were comparable in both groups. Sucralfate seems to be a valid alternative to H2-blockers in the treatment of reflux esophagitis.

Adult↗

Rioprostil in the acute and long-term treatment of peptic ulcers: a review.

The new prostaglandin E1 analogue, rioprostil, significantly accelerates healing and the elimination of pain in cases of peptic ulcer. The anti-ulcerous potency of this prostaglandin is equivalent to that of cimetidine. In comparison with ranitidine, there is a positive trend in favour of the H2-receptor antagonist, ranitidine, which has a more pronounced antisecretory effect than rioprostil. The differences in the healing rates during treatment with rioprostil and ranitidine are statistically significant in some cases, whereas those relating to pain alleviation are not. In contrast, the therapeutic efficacy of the two substances is almost identical in cases of Ulcus ventriculi. Rioprostil can be used with much the same success as ranitidine for preventing the recurrence of duodenal ulcers. The frequency of diarrhoea during rioprostil treatment, 300 micrograms b.d. and 600 micrograms nocte, is approximately 10%. In only about 1% of the patients does the rioprostil treatment have to be discontinued because of this adverse reaction.

Anti-Ulcer Agents↗

A single evening dose of rioprostil, 600 micrograms, in the treatment of acute duodenal ulcers.

When administered as 300 micrograms b.d. or as 600 micrograms once in the evening, the new prostaglandin E1 analogue, rioprostil, is capable of reducing nocturnal H+ activity (1200 h to 0800 h) by 52% and 74%, respectively (p less than 0.01). Diurnal acidity (0900 h to 1800 h), on the other hand, is only reduced by 33% and 15% (not significant). A single evening dose of rioprostil, 600 micrograms, is used successfully on 208 patients suffering from acute duodenal ulcer. After 2 weeks and 4 weeks of treatment, the healing rates are comparable to the high values obtained with ranitidine, 300 mg nocte (rioprostil, 600 micrograms nocte: 54.1% and 84.1%; ranitidine, 300 mg nocte: 54.4% and 89.9%). There are also no significant differences between the groups as regards symptomatic improvement. Severe diarrhoea and abdominal complaints do not occur with rioprostil, 600 micrograms nocte.

Adult↗

Circulatory counter-regulations induced by continuous administration of nitroglycerin.

In a placebo-controlled, double-blind, cross-over study in seven healthy volunteers, continuous transdermal administration of nitroglycerin over 48 h by means of Nitroderm TTS 10 evoked counter-regulations that interfered with the nitrate effects. These counter-regulations comprised an increase in sympathico-adrenal activity, manifested in elevated plasma levels of adrenaline and noradrenaline, and an internal hemodilution, readily perceptible from the decrease in the hematocrit readings. As a result, several of the circulatory effects of nitroglycerin were no longer in evidence, or much weaker on the second day of the study. The effects concerned were the reduction of systolic and diastolic blood pressure, the increase in heart rate, the prolongation of PEPc, and shortening of LVETc, and the change in digital-pulse morphology (increase in the a/b quotient). On the other hand, the increase in venous distensibility and the decrease in hematocrit were unaltered throughout the observation period. The attenuation of the action of nitroglycerin noticeable 24 h after application of the patches is, therefore, not indicative of any loss of effect of the substance per se, but due to the circulatory counter-regulations, which were largely confined to the arterial side of the circulation and scarcely affected the venous system. One or two hours after removal of the patches, counter-regulations had practically ceased.

Administration, Topical↗

[Protective effect of an antacid against acetylsalicylic acid].

The protective action of an magnesium-aluminum-antacid (Mucal-Gel) against acute doses of acetylsalicylic acid (ASA) was studied in healthy subjects (n = 30) by a double-blind cross-over method. The severity of the lesion was determined by endoscopy. In the corresponding placebo experiments, severe lesions of the gastroduodenal mucosa were seen after administration of 1500 mg ASA. These lesions could be prevented only in the presence of high doses of the antacidum mixture. It is concluded from these studies that protective actions against ASA can be achieved only if the intragastric pH-level is adequately raised above 3.5 and higher.

Adult↗

Electric burns of the lip.

Young children, usually aged between 1 and 3 years, are frequent victims of electric burns of the lip caused by contact with an electric plug or extension cord. In this article, the authors classify the various types of lesions in 19 cases of electric burns of the lip and discuss surgical treatment approaches.

Burns, Electric↗

[Comparison of three histometric methods for the comprehension of stimulating effects on the rat thyroid gland].

There exist some histometric methods for the morphological quantification of different strongly stimulating effects on the thyroid gland induced by drugs and/or other chemical substances in dependence upon dose and duration of application. But in respect of technical and temporal expense and also diagnostic statement, there are considerable differences between these recording procedures. Therefore we examined the 3 mostly used methods synchronously (i.e. determination of thyroid epithelial cell height, nuclear volume in thyrocytes, and estimation of relative volume parts in the thyroid gland by the point counting method) by investigating the thyroid glands of methylthiouracil-(MTU)-stimulated rats and corresponding controls in order to compare the diagnostic value and temporal expense. The largest temporal expense was required in the nuclear volume determination, the smallest in the point-counting method. On principle, all 3 procedures allow the determination of hypertrophic alterations but only by help of the point-counting method, also hyperplastic changes are recognizable. By nuclear volume determination, we found significant differences between central and peripheral parts of the thyroid gland. Therefore, to avoid the subjective error, it will be necessary to measure a large number of nuclei in many planes of the gland. Also the determination of epithelial cell high reinforces the subjective error because of the heterological structure especially in unstimulated thyroid gland. If the number of counting points is exactly determined and, full of sense, limited, the point-counting method allows a nearly complete measuring of the whole object to be tested within an acceptable investigation time. In this way, the heterological structure of thyroid gland will be regarded, and comparability and reproducibility are guaranteed on an high level.

Animals↗

[Personal experiences with kidney transplantation in the elderly].

From January 1987 to December 1988 226 cadaveric renal allotransplants were performed in the Kidney Transplant Center of the Friedrichshain Hospital. 38 of the recipients (17%) were older than 50 years. The results of transplantation are comparable with younger recipients, except a higher frequency of age-related urological complications of benign prostatic hyperplasia.

Adolescent↗

Effectiveness of a transdermal nicotine system in smoking cessation studies.

To investigate the effectiveness and tolerability of a transdermal nicotine system (TNS) as an aid towards easing smoking cessation, two double-blind placebo-controlled randomized field studies were performed. The TNS was available in sizes of 10, 20 and 30 cm2, delivering 7, 14 and 21 mg of nicotine per 24 h. A first study was undertaken in general medical practice by a group of 21 doctors (Practitioner Study). This study involved 199 nicotine-dependent cigarette smokers of whom 100 were allocated to the nicotine group and 99 to the placebo group. The second trial was performed in 112 young people, 56 in each treatment group, at the Universities of Basle and Zurich (University Study). The placebo and the nicotine groups were comparable in both studies. Participants smoking more than 20 cigarettes a day were treated with the 30-cm2 system and the others with the 20-cm2 system. When abstinence, as verified by CO measurements, was achieved, the next smaller system was applied. In the Practitioner Study, the double-blind treatment phase lasted for 12 weeks with consultations every month and in the University Study the consultations during the 9-weeks' treatment period took place every 3 weeks. Abstainers in both studies will be followed up until 12 months after treatment was begun. After 1, 2 and 3 months of treatment 41%, 36% and 36% of the participants in the nicotine group of the Practitioner Study were abstinent. The corresponding figures in the placebo group were 19.4%, 20.4% and 22.5%. The differences were statistically significant for all three months (p = 0.001; p = 0.018 and p = 0.043). Body weight did not increase in the TNS group, but did in the placebo group (+ 4.4 kg). The craving for cigarettes and withdrawal symptoms decreased more under nicotine substitution. Abstinence rates in the University Study were initially higher with 51.8% in the nicotine group and 28.6% in the placebo group after 3 weeks of treatment, but then declined to 42.9% after 6 weeks and 39.3% after 9 weeks in the nicotine group and to 25% and 19.6%, respectively, in the placebo group. The differences between the groups were statistically significant on all 3 occasions, with p = 0.012, p = 0.046 and p = 0.023.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

[Ranitidine ameliorates acemetacin and indomethacin-induced changes of the gastroduodenal mucosa, without modifying the pharmacokinetic behavior of both antirheumatic drugs].

12 healthy volunteers participated in this double-blind, randomized, cross-over study. All subjects were given indomethacin (50 mg tid) or acemetacin (60 mg tid) for 6 days in the presence and absence of ranitidine 300 mg at night. At day 6 120 minutes after the last morning dose an endoscopy was performed and the appearance of the gastric and duodenal mucosa was noted. In the indomethacin experiments mean lesion score averaged 2.2 +/- 0.2 (+/- SEM) when placebo was coadministered. In the corresponding acemetacin-series the lesions score was 1.6 +/- 0.1 (+/- SEM). A reduction in mucosal damage occurred in both NSAID-groups when ranitidine 300 mg at night was given concurrently: The mucosal lesions score was reduced to 1.7 +/- 0.2 and to 1.0 +/- 0.1 (+/- SEM), respectively. This protection afforded by ranitidine was significant when compared with placebo (p less than 0.05). In 8 subjects plasma concentrations of acemetacin and indomethacin were determined on day 1 and day 5. The AUC-values of indomethacin and acemetacin in the presence and absence of ranitidine were almost identical when analysed by the paired T-test. The mean plasma concentrations of both antirheumatic agents did not show any difference when coadministered with placebo or ranitidine. Our data suggest that 300 mg ranitidine at night improves the gastroduodenal tolerability of both indomethacin and acemetacin without affecting main pharmacokinetic parameters of both antirheumatics.

Adult↗

[Single evening administration of a new antimuscarinic agent telenzepine in therapy of acute duodenal ulcer. Results of a randomized double-blind comparative study versus pirenzepine].

A multicenter, double-blind, randomized controlled study was conducted in 314 duodenal ulcer patients to compare the efficacy and safety of the antimuscarinics telenzepine and pirenzepine in the treatment of duodenal ulcer. Patients received telenzepine 3 mg (156) once-daily at bedtime or 50 mg pirenzepine (158) two times daily for 2 weeks. If ulcerous lesions persisted treatment was extended to 4 weeks. Efficacy was assessed by relief of ulcer pain and endoscopic findings of ulcer healing. Safety was determined on the basis of side effects and results of laboratory tests. The 2- and 4-week healing rates achieved with telenzepine were 21.1 and 67.3%, respectively, and with pirenzepine they were 20.0 an 69.0%, respectively; the differences in healing rates for the two drugs were not statistically significant. Similarly both drugs provided satisfactory relief of pain. The incidence of untoward effects was 24.5% with telenzepine and 29.7% with pirenzepine, dryness of mouth being most prominent (20.4 vs. 19.3%). With telenzepine blurred vision was reported in a significantly lower rate compared to pirenzepine (0.7 vs. 4.2%, p less than 0.05). Clinically relevant abnormal laboratory tests were not observed. The present study shows for the first time that the newly developed antimuscarinic drug telenzepine is in a single nocturnal dosage regimen (3 mg nocte) as effective as pirenzepine (50 mg bid) in the treatment of duodenal ulcer.

Adult↗

[Endoscopic studies of gastroduodenal tolerance of 100 mg versus 500 mg acetylsalicylic acid daily: a randomized double-blind study with healthy probands].

Acetylsalicylic acid (ASS) is increasingly used in the prevention of cardiovascular diseases. In recent years lower daily ASS-doses (100-300 mg) have been given for this indication. However, only marginal knowledge is available about the upper GI-tolerability of ASS in this dosage regiment. In a randomized double-blind study we have evaluated the gastroduodenal tolerability of 100 mg ASS and 500 mg ASS daily in 20 healthy volunteers using upper GI-endoscopy. Both ASS-dosages have been taken over a period of 4 weeks. Endoscopic controls were performed at entry and repeated after 7, 14 and 28 days of treatment. 100 mg ASS daily induced during the whole period significant less gastroduodenal damages than 500 mg ASS daily (p less than 0.05). The lesion score of both groups on day 7 and day 28 were almost identical. Our data suggest that even low doses of ASS (100 mg daily) produced gastroduodenal injuries and that no adaptative phenomena did occur during the treatment period.

Adult↗