Biomedical subjects
E Weber
Publications and source records attributed to E Weber.
[Validation of electronic by conventional pain diaries].
A new type of electronic pain diary was validated in an open, randomized, crossover study. The main target variables were the comparison of the correctly realized pain assessment entries as well as the recording of the number of adverse events. Selected for the study were 20 patients, who were either hospitalized, partially-hospitalized or treated on an out-patient basis, with painful spondylogenic spinal syndrome or osteoarthritis of the trunk-proximal large joints. The patients were randomly-assigned to the two groups. The first group initially received the conventional diary and thereafter the electronic diary; the sequence was reversed for the second group. The drug therapy consisted of the NSAID, Ibuprofen, at an individually-adjusted dosage. Additional therapeutic measures were carried out by all the patients. The electronic pain diary proved to be equivalent to the conventional diary with regard to adherence of the pain assessment entry times. At a defined equivalence range of +/- 20%, the statistical comparison showed that the limits were never exceeded. The equivalence test of Anderson-Hauck showed a significance level of p less than 0.0001. The minimum equivalence range was +/- 2%. It therefore follows, that the conventional method of data recording can indeed be fully replaced by the electronic method. Comparing the individual data of the 16 patients, from whom entries with both the electronic as well as the conventional pain diaries were submitted, a clear tendency for increased entries on adverse events in the electronic diary (C.D. 6.4 +/- 10.5/E.D. 36.4 +/- 44.1) was demonstrated. No significant difference, however, was shown for the number of patients making data entries on adverse events in the electronic pain diary compared to those patients, who made their entries on adverse events in the conventional diary. According to the data from the physicians and patients, the Ibuprofen treatment results in an improvement in 90%/75% of cases, respectively. Likewise, the functional impairment of the affected joints as well as the swelling decreased markedly. The advantages of the electronic data recording system, i.e. closely-meshed controls can be carried out, transcriptional errors are minimized, data can be processed on-line, no possibility to subsequently change an entry, stand in contrast to the feature that there is no possibility to make free-style entries. The employment of the electronic system in the recording of individual data and subjective data represents a substantial improvement with regard to the quantity and quality of the data.
[The family group. In the field of tension between the families' expectations and the aims of the therapists].
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[Partial dentures (1)].
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Design and analysis of the HYPREN-trial: safety of enalapril and prazosin in the initial treatment phase of patients with congestive heart failure.
Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients.
[Clinical testing of new drugs in psychiatry].
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Distribution of Met-enkephalyl-Arg-Gly-Leu in rat larynx: partial coexistence with vasoactive intestinal polypeptide, peptide histidine isoleucine and neuropeptide Y.
Using light microscopic (LM) enzyme-immunohistochemistry on deparaffinized adjacent sections Met-enkephalyl-Arg-Gly-Leu (ME-RGL) immunoreactivity was found to partially coexist with immunoreactive neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in intrinsic laryngeal neurons of the rat. Further ME-RGL-immunoreactive (ir) fibres were found around glands in the subepithelium, in connective tissue of striated muscle and in the perichondrium, as well as around arterial and venous blood vessels. They frequently contacted mast cells and macrophages. The presence of ME-RGL indicates pro-enkephalin-related origin of this novel laryngeal opioid system. From the specific target relations and close interrelations of fibres staining for opioids with those staining for the other peptides--which are known to be more or less characteristic of the sympathetic (NPY), parasympathetic (VIP, PHI) and sensory (calcitonin gene-related peptide; CGRP) subdivisions of the peripheral nervous system--we deduce that opioid/non-opioid interactions might co-control various laryngeal functions, e.g. glandular secretion, blood flow, immune and inflammatory responses and/or might be of relevance in trophic mechanisms.
Inducible endothelin mRNA expression and peptide secretion in cultured human vascular smooth muscle cells.
This study demonstrates the induction of endothelin (ET) mRNA expression and synthesis of functional ET peptide in cultured human vascular smooth muscle cells (hVSMC). Compounds eliciting such responses in hVSMC include the vasoconstrictor hormones angiotensin II and arginine-vasopressin and the growth factors transforming growth factor beta, platelet derived growth factor AA and epidermal growth factor. Induction of ET mRNA expression in hVSMC exhibited transient kinetics (peak at 3-5 hrs. and return to basal within 7 hrs.) which differed from the more sustained ET transcript induction observed for porcine endothelial cells. ET peptide (determined by both radioimmuno- and radioreceptor assays) produced by stimulated hVSMC attained levels (approximately 120-160 pg/10(6) cells/4 hrs.; concentration approximately 3 x 10(-11) M) within the biologically effective concentration range of ET. Stimulated secretion of ET from hVSMC was abolished in the presence of the protein synthesis inhibitor cycloheximide. Sep-pak C18 extracts of medium from stimulated hVSMC elicited a concentration-dependent phosphoinositide catabolic response in myo-[2-3H]-inositol-prelabelled hVSMC. Our findings invoke a role for ET which extends beyond the paracrine regulation by peptide synthesized and secreted by endothelial cells. We propose that VSMC-synthesized ET may function in an autocrine manner to regulate both tone and structural modelling of vasculature.
[Pharmacokinetics of bismuth preparations in patients with gastritis and ulcer disease].
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A novel photoaffinity ligand for the phencyclidine site of the N-methyl-D-aspartate receptor labels a Mr 120,000 polypeptide.
A radiolabeled photoaffinity ligand has been developed for the N-methyl-D-aspartate (NMDA)-preferring excitatory amino acid receptor complex. [3H]3-Azido-(5S, 10R)(+)-5-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine [3H]3-azido-MK-801 demonstrated nearly identical affinity, density of binding sites, selectivity, pH sensitivity, and pharmacological profile in reversible binding assays with guinea pig brain homogenates to those displayed by its parent compound, MK-801. When employed in a photo-labeling protocol designed to optimize specific incorporation, [3H]3-azido-MK-801 labeled a single protein band which migrated in sodium dodecyl sulfate-polyacrylamide gels with Mr = 120,000. Incorporation of tritium into this band was completely inhibited when homogenates and [3H]3-azido-MK-801 were coincubated with 10 microM phencyclidine. These data suggest that the phencyclidine site of the NMDA receptor complex is at least in part comprised of a Mr = 120,000 polypeptide.
Monitoring compliance in clinical trials.
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Phorbol ester promotes a sustained down-regulation of endothelin receptors and cellular responses to endothelin in human vascular smooth muscle cells.
The effect of phorbol ester pretreatment of human vascular smooth muscle cells (hVSMC) was studied with respect to regulation of endothelin (ET)-receptor binding and cellular responses to ET. The capacity of hVSMC to bind ET was decreased (by approximately 50% at maximum) after phorbol exposure, and this reductive effect was both rapid (t 1/2 approximately 10 min.) and sustained (for up to 24 hrs. of chronic phorbol exposure). Phorbol pretreatment inhibited both inositol phosphate and diacylclycerol production responses of hVSMC to ET in a manner that was time-dependent and sustained. Phorbol pretreatment also produced a persistent reduction in the ability of ET to release isotopically-labelled arachidonic and/or its metabolites from hVSMC, but importantly ionomycin-stimulated release was similarly negatively affected. Furthermore, ET-induced accumulation of the phospholipase A2/phospholipase B-derived inositol phospholipid metabolite, glycerophosphoinositol, was not different between control and phorbol-treated hVMSC. The mechanism whereby phorbol exerts differential, but notably sustained inhibitory effects on ET-promoted signal transduction pathways are thus complex and illustrative of the selectivity of protein kinase C in regulating cellular responses.
Relationship between vessel wall 13-HODE synthesis and vessel wall thrombogenicity following injury: influence of salicylate and dipyridamole treatment.
We performed studies to determine the relationship between injured vessel wall thrombogenicity, vessel wall 13-hydroxyoctadecadienoic acid (13-HODE) synthesis and cAMP levels in rabbit treated with salicylate or dipyridamole. Injured vessel wall thrombogenicity was measured as the number of 3H-adenine labelled platelets adhered to the subendothelial basement membrane exposed by air injury in carotid arteries of rabbits treated orally with salicylate or dipyridamole. Vessel wall 13-HODE was measured by HPLC and vessel wall cAMP was measured by RIA. Vessel wall thrombogenicity was increased two-fold in rabbits treated with salicylate and decreased by half in rabbits treated with dipyridamole. The levels of vessel wall cAMP levels were correlated both with the plasma dipyridamole levels and increases in 13-HODE synthesis. cAMP levels were unaffected by salicylate treatment, but 13-HODE synthesis was decreased. We conclude that there is a significant relationship between vessel wall cAMP levels and 13-HODE synthesis, which in turn, influences subsequent vessel wall thrombogenicity.
Compliance with short-term high-dose ethinyl oestradiol in young patients with primary infertility. New insights from the use of electronic devices.
The objective of the study was to investigate patient compliance with ethinyl oestradiol therapy. Medication was prescribed to be taken in 20-micrograms doses four times daily for seven days. Oestrogens are prescribed for standardization of the cervical mucus before the sperm cervical-mucus penetration test (SCMPT) is performed. Relation of drug compliance with adverse drug reactions reported by the patients. The methodology used in this study was continual microprocessor-based monitoring by means of the Medication Event Monitoring System, MEMSTM. Adverse drug reactions were recorded by means of standardized interviews. Investigations were carried out on thirty female patients, mean age: 28.8 years (range 21 to 36 years), with primary infertility, mean duration of infertility: 3.9 years (range 9 months to 8 years). The results showed that individual patients' compliance was remarkably variable, ranging from 14.3% up to 136%. The average compliance was 65%. Less than 30% of the prescribed doses were taken on schedule. Administration of oestrogens was effective in all but one patient. High cervical indices were documented irrespectively of the dose taken. In answer to the questionnaire, 24 out of 30 women reported side effects, of which 79% were rated by the patients as being mild. The lower the drug compliance was, the more adverse reactions were reported. In patients who took more than 65% of the drug, this inverse relationship was statistically significant (r = -0.71, p = less than 0.01). Our conclusion is that the empirically fixed daily dose of 80 micrograms of ethinyl oestradiol for seven days appeared to be too high in regard of the observed dose response, i.e. cervical mucus quality. A dose finding study, including compliance monitoring, seems to be reasonable. Within further studies, a simpler dosage regimen should also be taken into account. The observed association between patients' reports of adverse effects and drug compliance deserves further investigation.
Risk factors as reflected by an intensive drug monitoring system.
Age and gender are often suspected to be risk factors predisposing to ADRs. Therefore the data obtained by the Heidelberg Intensive Drug Monitoring System were analysed for possible correlations between these two variables and the incidence of ADRs. Based on the medical records comprising the time period between 1980 and 1987 information was available on 70,500 admissions to the Heidelberg University Hospital, Department of Medicine. Age, gender, number of prescriptions and ADRs were analysed. The percentage of patients affected by ADRs rises with advancing age; however the number of prescribed drugs also increases. When the incidence of ADRs in various age groups was analysed in relation to prescription data, no effect of age could be found. In contrast there was a linear correlation between the overall incidence of ADRs (independent of age) and the number of prescriptions per patient (per single admission). These results clearly document that age does not seem to be relevant to the incidence of ADRs, but that the risk is related to the number of drugs prescribed to a particular patient.
Association of GP40/CD7+ acute myeloblastic leukemia and chromosome 5 aberrations.
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Dynamics of drug regimen compliance--its assessment by microprocessor-based monitoring.
The utility of a new microprocessor-based method for continuous monitoring of compliance in taking solid medicaments has been evaluated. Medication intake in 31 ambulant patients was assessed in a prospective observational study under the conditions of routine practice. The patients (aged 14-87 y, mean 50 y) were receiving long-term drug treatment for various chronic diseases. There was marked interindividual and intraindividual variation in compliance with different drugs. Deviations from the prescribed dosage regimens were caused by omission of doses (22.7% of prescribed doses) and intake of extra doses (5.6% of prescribed doses). Continuous monitoring revealed that in 19% of the monitoring period no medication was taken, in 13% there was partial intake, and in 8% extra doses were taken. Patient-initiated drug holidays occurred in 50% of patients. They were responsible for 76% of the medication-free time. It is concluded, that continuous compliance monitoring is practicable in ambulatory patients. It provides information about the dynamics of drug intake behaviour that cannot be obtained from medical histories or from clinical or laboratory examination. The information could be used effectively in individual patient care and in clinical drug trials.
Variation of benzbromarone elimination in man--a population study.
The plasma benzbromarone concentration-time profile in a healthy subject who retained the compound much longer than other individuals is described. The data suggested that determination of the 24 h plasma concentration of the parent drug after a single oral dose of 100 mg benzbromarone would be an appropriate procedure to determine the elimination phenotype. Based on this procedure, 148 of 153 healthy individuals (97%) in a population study were found to eliminate benzbromarone rapidly. In one subject the 24 h benzbromarone plasma concentration was very similar to that observed in the individual who had been more fully characterized. Four participants gave intermediate results. The data are compatible with a bimodal or trimodal distribution of different benzbromarone elimination phenotypes.