Liquid chromatographic determination of mianserin in plasma by fluorescence detection after on-line photochemical reaction.
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Biomedical subjects
Publications and source records attributed to R Schmid.
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Expert systems (ES) are a new tool for information processing developed by the branch of computer science known as artificial intelligence. ES are capable of solving problems in a given domain by using the knowledge and emulating the behaviour of specialists in that field. ES can be used as powerful tools for education since they are able to justify their own conclusions and to make the underlying reasoning explicit. This paper presents 'Vertigo', an ES aimed at the classification and diagnosis of different forms of dizziness. It has been conceived mainly as a teaching tool in otoneurological departments. The rationale of this project, its development, the structure and the use of the system are described. So far, 'Vertigo' has been tested on more than 200 cases of dizziness and is presently being used by ENT residents during their otoneurology stage.
In a double-blind placebo-controlled trial of 18 patients, methohexitone blocked objective signs of opiate withdrawal caused by a bolus injection of naloxone. Furthermore, in continuing the naloxone therapy for 48 hours, no withdrawal signs appeared. Levels of withdrawal distress returned to normal levels within six days. This approach can be regarded as an effective and well tolerated withdrawal therapy with low drop-out rates.
In the present study we have examined if the different composition of intravenously administered amino acid solutions is of importance for the effect of cholecystokinin (CCK) on pancreatic insulin and glucagon release in dogs. In 6 conscious dogs CCK-9 was infused intravenously at stepwise increasing doses of 5, 10 and 20 pmol/kg.h during an intravenous background infusion of Aminosteril or Aminoplasmal. Aminosteril contains more insulinogenic amino acids while Aminoplasmal contains more glucagonogenic amino acids. CCK elicited a significant stimulation of insulin levels by 10 microU/ml (p less than 0.01) in the presence of i.v. Aminosteril compared to that elicited by i.v. amino acids alone. Glucagon and glucose levels remained unchanged. During i.v. Aminoplasmal CCK-9 had no effect. Since in dogs the physiological plasma amino acid pattern following the ingestion of protein-rich meals is unknown the possibility cannot be excluded that in dogs CCK acts as a mediator of the intestinal signal which augments insulin release during ingestion of protein-rich meals.
The effect of equimolar doses of GIP and GLP-1 (7-36amide) on insulin and somatostatin secretion in the isolated perfused rat pancreas was compared. At a perfusate glucose concentration of 70 mg/dl GLP-1 (7-36amide) 10(-9) and 10(-8) M and GIP 10(-9) M elicited a significant stimulation of insulin while GIP 10(-8) M and lower doses of both peptides (10(-11) and 10(-10) M) were ineffective. At elevated perfusate glucose levels of 150 mg/dl both peptides stimulated insulin release at 10(-11), 10(-10), 10(-9) and 10(-8) M but not at 10(-12) M. The insulin response at the higher glucose level was significantly greater compared to the effect of the same doses at normoglycemic conditions. Somatostatin release was stimulated significantly by GLP-1 (7-36amide) at 10(-10) and 10(-9) M at perfusate glucose level 70 mg/dl. At a glucose concentration of 150 mg/dl this effect was abolished. GIP did not alter somatostatin release at a perfusate glucose concentration of 70 mg/dl while at 150 mg/dl only the highest dose of GIP (10(-8) M) stimulated somatostatin release significantly. In conclusion, the present data demonstrate that in vitro in the rat pancreas both peptides are equally effective secretagogues of insulin release at normal and moderately elevated perfusate glucose levels. In contrast, somatostatin secretion is stimulated by GLP-1 (7-36amide) at normoglycemic conditions while only a rather high and presumably pharmacological dose of GIP is a stimulus of somatostatin secretion at moderate hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
By the use of a monoclonal antibody reacting with the human glomerular basement membrane exclusively we have been isolating a specific glomerular antigen. The antibody failed to react with other renal structures and other basement membranes and extracellular matrix constituents of other organs or plasma proteins. It did not react with glomerular basement membranes of other species as mice and rats. For the isolation of the antigen we applied affinity chromatography, on Sepharose beads coupled to the monoclonal antibody PM II 34 G3. From this column the antigen was eluted under acid conditions. In 8% polyacrylamide gel electrophoresis the approximate molecular weight was estimated with 14400 daltons, which was confirmed on high pressure liquid chromatography using the Bio-Sil TSK method. The antigen was temperature sensitive in that at high temperatures (60 degrees C) several bands on SDS-PAGE and several peaks on HPLC could be noted. This could be responsible for the crystal formation after treatment/concentration on the rotary vacuum pump at 60 degrees C. Preliminary data of amino acid analysis showed a high glycine content pointing towards a collageneous molecule. But cross reactivity with many connective tissue proteins could be ruled out by immuno-histochemical techniques and affinity chromatography. A major point of interest is that this antigen can be detected in human urine under physiological conditions. We are herewith reporting the first species and organ specific glomerular basement membrane antigen.
Some authors have suggested that the smooth pursuit system (SPS) may be responsible for nystagmus suppression when a small visual target--stationary with respect to a subject receiving vestibular stimulation in the dark--is presented. Under five experimental conditions, post-rotational vestibular stimulations were combined in different ways with the presentation of a small visual target. The oculomotor responses of 15 normal subjects were recorded and analyzed. The characteristics of nystagmus suppression (latency, dynamics, and nonlinear behaviour) seem to be consistent with the hypothesis of SPS participation. A nonlinear mathematical model of the interaction between vestibulo-ocular reflex and SPS is presented. Computer simulation of the experimental conditions considered in this study provides theoretical results which closely approximate the actual experimental data.
The influence of vinpocetine on imipramine steady-state plasma levels was investigated in 18 healthy volunteers. Twenty-five mg imipramine were given t.i.d. for a total of 21 days, vinpocetine treatment was started on day 11 with 10 mg t.i.d. and continued until the end of the study. The AUC of imipramine plasma levels were obtained using consecutive imipramine plasma level determinations from samples drawn every 2 h from 8:00 a.m. to 8:00 p.m. by trapezoidal rule. AUCs of day 10 without and of day 21 during concomitant vinpocetine treatment were compared, demonstrating the independence of imipramine's bioavailability from concomitant vinpocetine treatment. There were no indications to assume a changed absorption of imipramine due to vinpocetine as would be reflected in Cmax and tmax values. Imipramine metabolization to the still effective metabolite desipramine shows a huge interindividual variability although it remains constant for the individual. The analysis of this parameter in the course of this study does not suggest that it is changed due to vinpocetine treatment.
Adaptation of young inmates with and without mental retardation to prison regime was examined. The mean number of disciplinary reports received across five categories of infractions were compared. Differences were evaluated with one-way analysis of variance and follow-up tests. Results indicated that (a) youthful mentally retarded and nonretarded prison inmates did not adjust to incarceration in a similar manner and (b) behavior in prison was significantly different across certain measures by group. Inmates with mental retardation demonstrated poor overall adjustment in prison.
Reported in this paper are eight cases of femoral fracture in childhood which were vertically extended according to Weber. Positioning is described in minute detail. Axial errors and lateral displacement were continuously reduced by extremely non-invasive reduction. Shortening and rotational errors were totally corrected.
Induced detoxification treatment of opiate addicts by means of naloxone was developed at the intensive care unit of the Department of Psychiatry at the University of Vienna. Two methods were tested 1. Rapid opiate withdrawal by means of a staggered naloxone regimen. 2. Ultrashort opiate detoxification during general anaesthesia using high doses of naloxone. In an open trial 15 patients were treated with staggered doses of naloxone while under tiapride. The various discomforts were satisfactorily reduced, and the detoxification syndrome was limited to 50 hours. In a second open trial 6 patients were administered 10 mg naloxone under general anaesthesia. All naloxone induced withdrawal syndromes can be suppressed by barbiturate anaesthesia. They do not appear even after the effect of the anaesthesia wears off if the patient is kept on a naloxone regimen as long as opiates remain present in the circulatory system. Both methods shorten detoxification treatment and provide smooth transition to a naltrexone maintenance programme.
To investigate the requirements for induction of cytotoxic T lymphocytes (CTL) by peptides we chose the 16-residue nucleoprotein peptide (NPP; 365-380) from the influenza virus A/NT/60/68 as model substrate that is recognized in conjunction with major histocompatibility complex H-2d. Here we present that CTL can be raised from naive animals by repeated in vitro stimulation with high concentrations of peptide. The frequency of this response can be boosted by immunization of the animals with NPP-conjugated to ovalbumin as a carrier. However, in contrast to NPP-specific CTL lines raised from virus-primed animals none of the peptide-induced CTL lines were able to lyse virus-infected targets. Although they did not show an apparent difference in fine specificity of the peptide recognized, their affinity to the target cells was 100-fold lower than that of CTL from virus-primed animals as estimated from the peptide concentration needed to achieve significant lysis. In addition, the activity of peptide-induced CTL was very sensitive to blocking by anti-CD8 antibodies as compared to virus-specific CTL. Furthermore, all peptide-induced CTL showed a high second reactivity for allogeneic H-2k targets. Therefore, it is argued that high epitope density achieved by high peptide concentrations can in vitro recruit lymphocytes of another specificity. For the tested peptide the reactive T lymphocytes showed high alloreactivity.
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To assess the activity of enoxacin, clindamycin and metronidazole, MICs of clinical isolates of saccharolytic intestinal Bacteroides spp. were determined, using the agar dilution method according to NCCLS guidelines. Checkerboard titrations of enoxacin-metronidazole and enoxacin-clindamycin were done on Wilkins-Chalgren agar; inoculation, incubation and reading of plates were as for determination of MICs. Metronidazole MIC 90s for Bacteroides fragilis (23 strains) and Bacteroides thetaiotaomicron (23 strains) were 0.5 mg/l, clindamycin MIC 90 for B. fragilis was 1 mg/l, and for B. thetaiotaomicron 8 mg/l, whereas enoxacin MIC 90 values were 16 mg/l and 64 mg/l, respectively. The evaluation of the inhibitory effects of the combination enoxacin-metronidazole for B. fragilis showed additional effects in eleven strains, indifference in seven strains and antagonism in one. The figures for B. thetaiotaomicron showed addition in five strains, indifference in 17 strains, antagonism in one. For B. fragilis the combination enoxacin-clindamycin showed addition in ten strains, indifference in six, and antagonism in one; for B. thetaiotaomicron synergism in one strain, addition in four strains, indifference in 17 strains. In conclusion, the absence of antagonism and the overall preponderance of additional and indifferent effects warrant the use of enoxacin in combination with metronidazole or clindamycin in clinical trials of treatment of anaerobic-aerobic mixed infections.
A new and simplified high-performance liquid chromatographic (HPLC) method for the determination of the antiestrogenic drug tamoxifen (TAM) and its desmethylated and hydroxylated metabolites in human plasma is described. Specific and sensitive fluorescence detection is achieved by "on-line" photochemical conversion of the TAM structure to a highly fluorescent phenanthrene product using a newly developed post-column photoreactor included in the HPLC system. A highly selective chromatographic separation was established by using unmodified silica with aqueous mobile phase for separation, with the sample preparation step on a small CN-propyl pre-column, included in the HPLC system. Due to the high specificity of the separation and detection system, even small volumes of deproteinized plasma sample can be injected directly without prior sample extraction. The described method permits a very fast and reproducible determination of TAM and its two major metabolites in plasma on a routine basis, down to 100 pg ml-1 concentration.
This, then, is my vision of medical education in the next millennium: a deep and fruitful integration of basic science and clinical medicine; a gradual adaptation of the curriculum to reflect the realignment of scientific and clinical specialties; and a value system mandating that growth and expansion be immutably linked to maximal intellectual and educational returns.
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Protein-rich meals stimulate secretion of insulin, glucagon, and pancreatic polypeptide (PP) from the endocrine pancreas. On the one hand, this is due to increased levels of circulating amino acids, and, on the other, neural and/or endocrine factors can contribute to activation of islet cell function. The present study was designed to determine, first, pancreatic endocrine function and postprandial amino acid levels after a protein and a protein-carbohydrate meal and second, insulin, glucagon, and PP levels during infusion of amino acid mixtures that imitate the postprandial amino acid pattern. In healthy volunteers the ingestion of a protein-rich meal (300 g tenderloin steak) elicited within 1 h an increase of virtually all amino acids by 20-400 mumol/L above basal values. The infusion of two different amino acid solutions available for use in humans showed that Aminosteril-N-Hepa (AS) was better for the imitation of the so-called "insulinogenic" amino acids while Aminoplasmal L-10 (AP) gave more comparable plasma levels of the "glucagonogenic" amino acids. Both solutions were not able to imitate the postprandial amino acid pattern completely. With regard to insulin levels, both solutions gave a comparable increase, while AP but not AS stimulated glucagon and PP levels. This suggests that circulating amino acids may be responsible for 60% of the postprandial insulin response after a protein meal, while their contribution to glucagon release can only be roughly estimated at 30-60%. The contribution of circulating nutrients to the greater insulin response after the protein-carbohydrate meal was comparable (60%), while the attenuated glucagon response can be ascribed almost completely to the effect of circulating nutrients. In conclusion, the present data demonstrate that the composition of amino acid mixtures is as yet not ideal for a complete imitation of the postprandial amino acid pattern. The insulin, glucagon, and PP response depends on the amino acid mixtures and accordingly the respective plasma amino acid concentrations obtained during infusion studies. The adequate imitation of plasma amino acid levels is of critical importance for the evaluation of absorbed and circulating amino acid effects in the postprandial state.