Biomedical subjects
Publications and source records attributed to P Müller.
The results of the operative treatment in 33 patients suffering from pelviureteral obstruction and of the follow-up control using ultrasonography and renography are presented. A reduced radiation exposure and diminished treatment costs are the results of this changed diagnostic and therapeutic strategy.
In a randomized double-blind study the gastroduodenal tolerability of 300 mg ASS daily has been evaluated in the presence of 150 mg ranitidine bid or placebo in 20 healthy volunteers using upper GI-endoscopy. The treatment period lasted 14 days. Endoscopic controls were performed at entry, and repeated at day 7 and day 14. At entry, the mean endoscopic score averaged 0.8 +/- 0.1 in the ASS/placebo-group and 1.0 +/- 0.0 in the ASS/ranitidine group. 300 mg ASS daily induced in the placebo experiments marked gastroduodenal alterations both at day 7 and day 14 (4.7 +/- 1.2 and 6.5 +/- 2.1, respectively). Concomitant administration of 150 mg ranitidine bid afforded almost full protection against 300 mg ASS daily both on day 7 and day 14 (1.9 +/- 0.6 and 2.1 +/- 0.8, respectively) (p less than 0.05). Our data suggest that coadministration of ranitidine 150 mg bid reduces almost completely gastroduodenal lesions evoked by acetylsalicylic acid 300 mg daily.
Healthy nicotine-dependent smokers were applied different doses of transdermal nicotine systems (TNS) during single and repeated administrations. Plasma and urine nicotine and cotinine concentrations were determined by high performance liquid chromatography (HPLC). After single application of TNS, the maximal concentration (Cmax) and area under curve (AUC) of nicotine in plasma as well as the amount of nicotine excreted in urine were linearly related to the dose. The stable urinary cotinine excretion was not influenced by the amount of nicotine delivered by the TNS. The relevant 24 h plasma nicotine concentration reached after TNS application compares well with the plasma nicotine footpoints--not the peaks--observed in moderate to heavy cigarette smokers. A comparison between different nicotine doses from different TNS allowed to conclude to the functionality of the systems as regards pharmacokinetics and bioavailability. One or two hours after removal of the systems, there was a very slow decline of the nicotine concentrations. After repeated application of TNS, there was evidence for only a very limited nicotine accumulation in plasma (+14%) or in urine (+9%) over 10 days. The steady-state of nicotine was reached within 4 days. The continuous delivery of nicotine over 24 h resulted in an early morning plasma concentration which probably decreases or prevents the craving for the first cigarette.
To define the pharmacological properties of a newly developed transdermal nicotine system (TNS) designed to facilitate abstention from smoking, three human pharmacology studies were performed in healthy, nicotine-dependent smokers. The first study, in which cigarette smoking served as the standard mode of nicotine intake, was carried out to evaluate the most suitable non-invasive methods for detecting the pharmacodynamic effects of nicotine and to provide a baseline for comparisons with the results of the subsequent studies to assess the effects of single and repeated applications of the TNS. The pharmacodynamic changes induced by smoking were generally most pronounced after the first cigarette following 10 hours' abstinence. The most sensitive parameters were heart rate, which increased, stroke volume measured by impedance cardiography, which decreased, cutaneous blood flow measured by Laser Doppler flowmetry and skin temperature, which diminished to a statistically significant extent after each cigarette. Increases in blood pressure were not very pronounced. Plasma catecholamines were consistently elevated after each cigarette, but the changes were not statistically significant. Compared with those induced by cigarette smoking, the cardiovascular effect seen after either a single application of the TNS (10, 20 and 40 mg/24 h) or repeated application of a TNS delivering 14 mg nicotine/24 h were minor. A slight increase in blood pressure was detectable only on the first day of application and had disappeared after 10 days' repetitive application, suggesting the development of partial tolerance. Heart rate was slightly increased by 3-7% and stroke volume decreased by 5-12% on the tenth day of TNS application.(ABSTRACT TRUNCATED AT 250 WORDS)
The relationship between the course of illness and the therapeutic circumstances was investigated in 6 cases of schizophrenic patients who had committed suicide. All patients committed suicide following repeated stationary treatments with only partial remission. More than previously reported in the literature insufficient treatment on one side and a breakdown of the therapeutic relationship to the doctor with the following repulsion and hopelessness on the other side appear to determine the suicidal dynamics in the context of a multidimensional concept of suicide: If insufficient therapeutic efficacy disappoints doctor and patient and if the patient cannot fulfill rehabilitation requirements, he is often given up and then gives up himself. From that, suicideprophylactic aspects should be derived.
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Data have been compiled concerning insecticide-resistance in native populations of Musca domestica from 10 districts of the GDR for the period between 1976 and 1988. The insecticides tested were trichlorfon, dimethoate, bromophos, and trichlophenidine, i.e. those insecticides commonly used in house fly control on animal production farms. Pyrethrum and permethrin were also tested. Since the test strains were frequently selected in connection with control failures, the data may not be representative for all populations. But they allow some conclusions concerning the development of resistance. A stage of development has been reached which required a departure from the exclusive use of conventional procedures (residual spraying of surfaces with persistent contact pesticides). Intensified research on non-chemical or special chemical methods is urgently needed.
The effects of single oral doses of 800 and 1200 micrograms of the new alprostadil analogue mexiprostil (prostaglandin E1 16-methyl-16-methoxy derivative, MDL 646), presented as tablet and capsule formulation, on basal and pentagastrin-stimulated acid secretion, were studied in 10 healthy volunteers, using a randomized, double-blind, placebo-controlled, 5-way crossover design. Compared to placebo, administration of mexiprostil resulted in a significant inhibition of basal gastric acid secretion, at both doses and formulations. Pentagastrin-stimulated gastric secretion was reduced to a lesser degree and the differences compared to placebo did not achieve statistical significance when adjustments were made for basal effects present before starting stimulation. Total volume of gastric secretion, under basal conditions, was decreased by both doses and formulations, though the changes were significant only at 1200 micrograms for both formulation. The decrease in volume of gastric secretion during pentagastrin infusion did not reach statistical significance. Basal intragastric pH was increased by both doses and formulation, but the changes were significant only for the capsule formulation, at either dose. Neither dose of mexiprostil prevented the decrease in intragastric pH produced by pentagastrin infusion. Tolerability of mexiprostil was excellent with no unwanted effects reported either during or after the study. No changes in heart rate and systemic blood pressure were observed. Laboratory safety parameters were not altered by mexiprostil. There was no significant difference between the effects of both formulations of mexiprostil on any pharmacodynamic parameter.
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The applications of microsurgery in the reconstruction of the injured ureter using a double-layer end-to-end anastomosis and in the repair of ureteropelvic junction obstruction using modified pyeloplasty techniques are described in detail. The advantages of the use of microsurgical techniques in reconstructive surgery of the upper urinary tract are elimination of routine urinary diversion, shorter duration of hospitalization and a higher success rate. Therefore, the application of microsurgery is cost-saving.
In a long-term experiment on rabbits 0.2% peracetic acid (0.5% Wofasteril) was distributed upon the dorsal skin, the oral and the vaginal mucosa 3 times per week for 12 months. Each type of tissue was applied 153 individual doses. The histological examinations did not yield dysplasias in the sense of a carcinogenic action of peracetic acid. Despite the very high dosage as it will never be demanded in therapeutical measures, the mucosal tissues under study neither showed inflammations nor scar formation after 12 months of administration. Merely in the dorsal skin a loss of minute accessory hairs in the animal fell was observed. From morphological points of view it seems justified to extend the indication of 0.2% peracetic acid (0.5% Wofasteril) to the mucosal membrane for preparatory arrangements of surgical interventions and for therapeutical measures in bacterially induced inflammatory processes. Clinical testing can be recommended. Before permanent use of peracetic acid for hand disinfection the possible hazards of depilation must be tested dermatologically.
Among eight strains carrying acridine-induced mutations in hisH, five which mapped at four different sites in the promoter-distal region of the gene showed His+ phenotypes on media containing a purine. By complementation analysis, hisH enzyme was shown to be required for growth on purines. Purine-sensitive His+ revertants of strains able to grow on purines carried second-site mutations which in one case could be shown to map in hisG. Strains able to grow on purines were able to grow on 2-thiazolyl-DL-alanine, too. We conclude that frameshift mutations in the promoter-distal part of the hisH gene of E. coli do not completely abolish the activity of the gene product.
Pronounced and sustained inhibition of acid secretion is currently the therapeutic principle most frequently applied in the treatment of peptic ulcer disease. Since theoretically short term risks of complete inhibition of acid secretion cannot be totally ruled out, anti-secretory anti-ulcer drugs should interfere as little as possible in the physiology of gastric acid secretion. This concept is presently best achieved through the single bedtime dose of H2-blockers, which has been shown to be as effective as a twice daily dosage regimen in peptic ulcer disease. This reduces only nocturnal acid secretion, while daytime acidity remains unaffected. But there is a close correlation between the extent of the reduction of nocturnal acid secretion, healing rates and pain relief. Additionally, large clinical trials with peptic ulcer patients have shown that after 14 days' treatment with H2-blockers 30 to 50% of patients still complain about ulcer pain and about 20 to 40% of patients take supplementary antacids. As a result of this there is undoubtedly a need for an additional medication that produces a more pronounced reduction of acidity than current treatment with H2-receptor antagonists as a single evening dose. Obviously this dosage regimen does not always fulfil the therapeutic requirements (i.e. pain relief) of the individual patient. Therefore a more flexible form of application should be introduced. In general clinical use it is not feasible to identify patients with a higher treatment requirement by acid secretion analysis. However, what is feasible is the recommendation to increase the dose and frequency of administration of H2-blockers in relation to the symptoms of pain.
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46 patients with rheumatic diseases suffering from dyspepsia and endoscopically proven gastroduodenal lesions entered a double-blind placebo-controlled study with ranitidine 150 mg b.i.d. over 4-8 weeks. The patients had to be treated for at least 3 months with the non-steroidal antiinflammatory drugs (NSAID) Diclofenac, Indomethacin, and Piroxicam before entering the study. During the trial all patients had to continue on NSAID. At entry patients in the placebo group (n = 23) had a total number of 33 gastrointestinal lesions of grade 1-3. In the ranitidine group (n = 23) a total number of 28 gastrointestinal lesions had been counted. After 4 weeks of treatment the number of lesions had been reduced in the placebo group to 20 and in the ranitidine group to 6 (p less than 0.05). The total damaging score at entry averaging 2.0 under placebo and 1.0 under ranitidine had been reduced to 1.3 (placebo) and 0.3 (ranitidine). (p less than 0.05). Our results underline the efficacy of ranitidine in the treatment of NSAID-induced gastroduodenal mucosal lesions.