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R Vos

Publications and source records attributed to R Vos.

36 records · Page 2Linked to original sources
PubMed2000

Text-based discovery in biomedicine: the architecture of the DAD-system.

Current scientific research takes place in highly specialized contexts with poor communication between disciplines as a likely consequence. Knowledge from one discipline may be useful for the other without researchers knowing it. As scientific publications are a condensation of this knowledge, literature-based discovery tools may help the individual scientist to explore new useful domains. We report on the development of the DAD-system, a concept-based Natural Language Processing system for PubMed citations that provides the biomedical researcher such a tool. We describe the general architecture and illustrate its operation by a simulation of a well-known text-based discovery: The favorable effects of fish oil on patients suffering from Raynaud's disease [1].

Drug-Related Side Effects and Adverse Reactions↗
PubMed1999

Cardiovascular drugs: discrepancies in demographics between pre- and post-registration use.

OBJECTIVES: To study discrepancies in demographic characteristics between patients participating in pre-registration phase III trials of cardiovascular drugs, registered in the Netherlands, and patient populations in daily practice representing the actual users of the drugs after registration. METHODS: Comparison of age and sex distribution in registration files of 15 cardiovascular drugs [angiotensin-converting enzyme (ACE)inhibitors/angiotensin II receptor antagonists, calcium channel blockers, beta-adrenergic blocking agents, vasodilators, HMG-CoA reductase inhibitors and thrombolytics] with patients selected from a general practitioner (GP) registration database, who had received prescriptions for drugs from the therapeutic classes for the registered indications (hypertension, hypercholesterolaemia or angina pectoris) or were diagnosed with myocardial infarction. Moderate discrepancy was defined as more than 10% difference between the populations, large discrepancy by more than 20% difference. Clinical trials were also analysed by region of trial performance with respect to patient selection criteria, differences in male/female ratios and ethnic origin of patients. RESULTS: Phase III clinical trials in registration files of drugs registered for hypertension, angina pectoris and myocardial infarction had a moderate to large under-representation of female patients. Patients aged more than 65 years, who accounted for more than 50% of drug use indicated for hypertension, angina pectoris and myocardial infarction, were under-represented in the clinical trials of drugs registered for all indications. Trials performed in North America included relatively fewer female patients compared with European trials, and showed different patterns in the ethnic origin between indications. CONCLUSIONS: Clinically relevant subgroups of cardiovascular patients are under-represented in pre-registration phase III trials. These findings concern major areas of cardiovascular diseases, i.e. hypertension, hypercholesterolaemia, angina pectoris and myocardial infarction. Widely used therapeutic classes of drugs are affected and regional differences in trial performance are present.

Adult↗
PubMed1999

[Not Available].

Explore the source record for details and available documents.

Drug Industry↗
PubMed1998

Natural defenses and autoprotection: naturotherapy, an old concept of healing in a new perspective.

Recent molecular-biological and molecular-genetic research has shown that important cellular-based autoprotective mechanisms are mediated by heat-shock proteins (HSPs) or stress-response proteins, also called 'chaperones'. This can happen because cells react to extracellular stimuli by activating signal transduction pathways which result in activating the genetic program. Molecular biologists and cardiologists are tempted to evaluate these phenomena in respect to their potential meaning for a better understanding of the complex notions of health and disease. When molecular geneticists or cardiologists talk about autoprotective or natural defense mechanisms, and physicians talk about salutogenesis, they all mean something very specific. The phenomenon seen here belongs to the body's own defense mechanisms which make it capable of reacting to harmful influences and allow it to stabilize a structure and/or function of the body for a certain period. Here we see a connecting link to the historically grounded term self-healing forces, which has challenged medical doctors in the different historical periods of medical science. They tried to explain these effects based on the current model of the organism. Their understanding of this phenomenon played a role in defining the concept of health and disease. Thus, it seems very fitting to look back into history, since the phenomena discussed here as well as the insights into autoprotective mechanisms will continue to influence medical understanding of health and disease.

Animals↗
PubMed1998

Mechanisms of autoprotection and the role of stress-proteins in natural defenses, autoprotection, and salutogenesis.

We hypothesize that in all physiotherapeutically oriented procedures of naturotherapy -- such as helio-, climate-, thalasso- or hydrotherapy or certain forms of physical exercise -- the transient expression of stress-proteins (heat-shock proteins, HSPs) is an important element of salutogenesis. These therapeutical procedures all cause a transitory 'disturbance' by an unspecific stressor that leads to functional responses. These functional responses can be trained and thus increase the forces and the capacity for resistance of the organism. The autoprotective mechanisms which we want to deal with in more detail are based on the functions of the heat-shock proteins (HSPs, stress-response proteins, 'chaperones') and represent archaic autoprotective responses. In addition, more complex mechanisms of autoprotection seem to have evolved that may play a role in the natural defenses against disease and which show a hierarchy of various genomically conserved strategies with different time-constants and time windows. This becomes apparent by studying autoprotective responses of the cardiovascular system of warm-blooded animals under ischemic stress. Recent extensive experimental protocols and clinical observations in elucidating the molecular basis of cardiac ischemia show that powerful autoprotective mechanisms are involved in the phenomena of 'hibernation', 'stunning', and 'ischemic preconditioning'. The system of the heat-shock proteins may therefore be regarded as a basic model for the principle of autoprotection and salutogenesis.

Animals↗
PubMed1997

A phase I dose finding study of a biweekly schedule of a fixed dose of cisplatin with increasing doses of paclitaxel in patients with advanced esophageal cancer.

We performed a phase I study of a fixed dose of cisplatin combined with increasing doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given in a biweekly schedule to determine the maximum tolerated dose in patients with advanced esophageal cancer. The starting dose was cisplatin 60 mg/m2 and paclitaxel 100 mg/m2, given by intravenous infusion every 2 weeks. Patients were re-treated when the granulocyte counts were greater than 0.75 x 10(9)L and the platelet counts were greater than 75 x 10(9)/L. The paclitaxel dose has been escalated to 160 mg/m2 and the maximum tolerated dose has not yet been reached. At the higher dose levels, more grade 3 and 4 granulocytopenia was observed, but no patient had to be hospitalized because of febrile neutropenia. Nonhematologic toxicity was mild at all dose levels. Increasing the dose of paclitaxel from 100 mg/m2 to 160 mg/m2 leads to an approximately 50% increase in the dose intensity, as calculated in milligrams per square meter per week (mg/m2/wk) over six cycles. Of the 31 patients evaluable for response, 17 (55%) achieved either a partial or a complete response. In conclusion, biweekly administration of cisplatin and paclitaxel, with re-treatment at a granulocyte level greater than 0.75 x 10(9)/L, is feasible and well tolerated, and has a promising response rate in patients with advanced esophageal cancer. Further accrual is ongoing to determine the maximum tolerated dose of this schedule.

Adult↗
PubMed1996

Fluorescence study of the conformational properties of recombinant tick anticoagulant peptide (Ornithodorus moubata) using multifrequency phase fluorometry.

Steady-state and multifrequency phase fluorometry were used to characterize the conformational state and conformational dynamics of recombinant tick anticoagulant peptide (Ornithodorus moubata) (TAP). The TAP contains two tryptophan residues at positions 11 and 37. The fluorescence emission varies sigmoidally as a function of pH with a pKa of 6.01 +/- 0.07. This pH dependency suggests that tryptophan fluorescence is quenched by His43 at low pH. This is confirmed by modification of the histidine with diethylpyrocarbonate. At pH 9 the fluorescence decay is well described by a sum of three exponentials (0.52, 1.9 and 5.4 ns), which decrease all three at pH 4 (0.25, 1.61 and 4.4 ns). From the reactivity of the fluorescence lifetimes toward N-bromosuccinimide and from the calculation of the accessibility we can attribute the long lifetime to Trp11, the short one to Trp37 and the middle one to both. The anisotropy decay was resolved into two components of 3.85 ns and 0.27 ns at pH 4 and 4.5 ns and 0.6 ns at pH 9. The long anisotropy decay time corresponds to the rotational correlation time of the protein, the short one to local mobility of the tryptophan residues.

Animals↗
PubMed1995

How adverse drug reactions can play a role in innovative drug research.

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

Phospholipid binding and lecithin-cholesterol acyltransferase activation properties of apolipoprotein A-I mutants.

Recombinant human apolipoprotein A-I (apo A-I) and three deletion mutants: apo A-I(delta Leu44-Leu126), apo A-I(delta Glu139-Leu170), and apo A-I(delta Ala190-Gln243), purified from the periplasmic space of Escherichia coli, were studied. The rate of turbidity decrease following mixing of apo A-I(delta Ala190-Gln243) with dimyristoylphosphatidylcholine (DMPC) vesicles at 23 degrees C was 10-fold lower than that of the other apo A-I proteins, confirming that the carboxy-terminal region of apo A-I plays a role in rapid lipid binding. The Stokes radii of reconstituted high-density lipoproteins (rHDL), containing dipalmitoylphosphatidylcholine and cholesterol, were larger for the three apo A-I mutants [6.3 nm for apo A-I(delta Leu44-Leu126), 6.1 nm for apo A-I(delta Glu139-Leu170), and 6.5 nm for apo A-I(delta Ala190-Gln243)] than for intact apo A-I (5.0 nm). The mutant rHDL all contained 4 apo A-I molecules per particle as compared to 2 for intact apo A-I. Circular dichroism measurements revealed 8 alpha-helices per apo A-I molecule, 5 per apo A-I(delta Leu44-Leu126), 6 per apo A-I(delta Glu139-Leu170), and 4 per apo A-I(delta Ala190-Gln243) molecule as compared to predicted values of 8, 5, 6, and 6 alpha-helices, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Fluorescence study of the three tryptophan residues of the pore-forming domain of colicin A using multifrequency phase fluorometry.

We have identified the steady-state and time-resolved fluorescence of the three tryptophan residues (Trp-86, Trp-130, and Trp-140) of the pore-forming domain of colicin A using site-directed mutagenesis in order to construct two- and one-tryptophan-containing mutant proteins. Fluorescence lifetimes were measured via multifrequency phase fluorometry. The fluorescence of the pore-forming domain of colicin A is dominated by Trp-140 which contributes almost 53% to the fluorescence intensity. Mutation of Trp-140 results in a decrease in fluorescence quantum yield and average lifetime. Colicin A wild-type and all mutant proteins display multiple lifetimes which belong to three different lifetime classes: 0.38-0.57 ns for tau 1, 1.6-1.87 ns for tau 2, and 3.6-4.41 ns for tau 3 at pH 5. At pH 7, the three classes are 0.64-0.89 ns for tau 1, 2.01-2.19 ns for tau 2, and 4.23-4.94 ns for tau 3. This pH effect influences all the lifetimes and must be attributed to a general conformational change. In wild-type colicin A, tau 3 originates mainly from Trp-140 while Trp-86 and Trp-130 both provide a major contribution to tau 2. The pH dependence of the fluorescence intensity gives rise to a pKa of 5.2. The different lifetime components of two of the three single-tryptophan-containing mutants show different quenching properties toward acrylamide, indicating that each lifetime is coupled to a different microenvironment. The linear combination of the lifetimes of the single tryptophans into pairs simulates very well the behavior of the two-tryptophan-containing mutants except for one, the mutant containing Trp-86 and Trp-130. The lifetimes of the wild-type protein can only be obtained by the linear combination of the lifetimes from the mutant containing the tryptophan pair Trp-86/Trp-130 and the mutant containing Trp-140. Mutual energy transfer between Trp-86 and Trp-130 is assumed to be the explanation of this deviation since the mutant proteins display no structural or dynamic aberrances. The calculated energy transfer efficiency amounts to 65% for energy transfer from Trp-86 to Trp-130 and 21% for the reverse transfer and is in agreement with our measurements.

Colicins↗
PubMed1995

Interaction between human alpha1-acid glycoprotein (orosomucoid) and 2-p-toluidinylnaphthalene-6-sulfonate.

The interaction between human alpha1-acid glycoprotein (orosomucoid) and the fluorescent probe, 2-p-toluidinylnaphthalene-6-sulfonate (TNS) has been studied. An association constant of 16.7 (+/- 3) x 10(3) M-1 was obtained for the complex at 20 degrees C with a stoichiometry of 1:1. From the effect of temperature on the binding process, the standard enthalpy change for the binding is calculated to be delta H0 = -18 +/- 3 kJ mol-1 and the standard entropy change delta S0 = 19 +/- 12 J K-1 mol-1. The tryptophan fluorescence of the protein can be described by a sum of three exponentials. Upon TNS binding, the average fluorescence lifetime of the protein in the complex changes much less than the fluorescence intensity. The bound TNS is therefore a very efficient acceptor for the protein fluorescence. The TNS bound to orosomucoid present two fluorescence lifetimes 11 and 4.3 ns. The possible origins of the two lifetimes are discussed.

Fluorescent Dyes↗
PubMed1994

Interactive individualization: patient counselling and drug information supported by knowledge systems.

A model for computer-supported patient counselling and drug information in community pharmacies is described. Two types of informational need are distinguished: the subjective informational need, i.e. the informational need perceived by the patient himself, and the normative informational need, i.e. the patient's informational need according to the professional. Accordingly, individualization is defined as the fine-tuning of information to the informational needs of the participants in the process of communication. A computer-supported process of communication based on this model is defined as 'interactive individualization'. The task of this knowledge system is to support the interactive encounter of the professional and the patient. The process of providing information consists of two subtasks: determining the items of information, e.g. pregnancy, dosage, etc., and subsequently determining the content of information or the advice itself. Based on these subtasks several functionalities of the proposed knowledge system can be derived.

Artificial Intelligence↗
PubMed1994

A fluorescence study of tryptophan-histidine interactions in the peptide anantin and in solution.

Anantin is a heptadecapeptide in which the C-terminal peptide chain pierces the covalently cyclized peptide ring formed by an amide link between the alpha-NH2 end group and the beta-carboxyl group of Asp(8). It contains a tryptophan and a histidine at positions 5 and 12, respectively. Des-Phe(17)-anantin lacks the C-terminal phenylalanine. Fluorescence emission intensity as a function of pH follows the ionization of a single residue. The pKa amounts to 7.23 +/- 0.03 for anantin and is attributed to His(12). At pH 9 the quantum yield is 0.12 +/- 0.01 for anantin, whereas at pH 4.5 the quantum yield decreases more than two-fold (0.05 +/- 0.01). Practically identical parameters are observed for des-Phe(17)-anantin. This pH dependency reveals intramolecular quenching of the excited indole ring of Trp(5) by the imidazole of His(12), which results in a marked decrease of the tryptophan fluorescence at low pH. In a multifrequency phase fluorometric study the fluorescence lifetimes for both peptides at pH 4.5 and pH 9 are determined. At both, pH fluorescence decay is well described by a sum of two exponentials. For anantin at pH 4.5 the lifetimes are 0.72 +/- 0.07 ns and 1.67 +/- 0.07 ns. At pH 9 the lifetimes are 1.11 +/- 0.12 ns and 2.55 +/- 0.03 ns. In methanol we find two lifetimes for anantin: 0.68 +/- 0.01 ns and 2.57 +/- 0.01 ns. The lifetimes are found to be slightly dependent upon emission wavelength. For des-Phe(17)-anantin practically the same values are observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Different effects of amiodarone on transport of T4 and T3 into the perfused rat liver.

Uptake and metabolism of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were studied in isolated perfused livers of control and amiodarone-treated rats (40 mg.kg body wt-1.day-1, 22 days). With the use of this perfusion system and a two-pool model describing thyroid hormone kinetics, total uptake was evaluated by the half-time (t1/2) of the fast component of the biphasic thyroid hormone disappearance from the medium and by the fractional influx rate constant (k21). Metabolism was assessed by the t1/2 of the slow component, by determination of breakdown products in medium and bile, and by thyroid hormone disposal according to the two-pool model. Disposal was corrected for differences in mass transfer into the metabolizing pool. In amiodarone-treated rats, both uptake and metabolism of T4 were decreased. Furthermore, it was shown that only transport into the metabolizing liver compartment and not uptake into the nonmetabolizing liver compartment was decreased. Both uptake and total metabolism of T3 were unaffected by amiodarone. The results showed that the different transport systems for T4 and T3 described in isolated rat hepatocytes may also be operative in the intact rat liver. Furthermore, it can be concluded that the low-T3 syndrome, caused by treatment with amiodarone, may be due to both impaired transport and impaired 5'-deiodination.

Amiodarone↗
PubMed1992

The gap between legal rules and practice in advertising non-registered pharmaceutical products. A new method of analysis.

The market of non-registered pharmaceutical products is growing fast in number and overall costs, not only in the Netherlands, but also in other European countries. These products often give the impression that the consumer may expect 'an effect as from a drug'. Legally, there is a clear distinction between 'drugs' and 'commodities' in the Netherlands; the question is whether legislation and practice concur. In an investigation we analysed texts of advertisements for non-registered pharmaceutical products published in a popular magazine. A method was developed, based on the legal definition of a drug and jurisprudence, to determine in a qualitative and quantitative way the application of medicinal claims. It transpired that in 65% of the analysed advertisements explicit or implicit claims were made. These products should therefore be subject to drugs legislation. Thus, in the Netherlands there is a gap between legislation and practice in advertising non-registered pharmaceutical products.

Advertising↗
PubMedDate not supplied

Development of pharmaceutical care in The Netherlands: pharmacy's contemporary focus on the patient.

OBJECTIVE: To describe how developments in the pharmacy profession in The Netherlands converged into the current movement toward pharmaceutical care. SETTING: Dutch community pharmacy. DESCRIPTION: Literature was reviewed for key elements of pharmacists' professional development over the last 40 years--the pharmacist-physician relationship, the pharmacist-patient relationship, the education of the pharmacist, provision of information to patients, medication surveillance, clinical pharmacy, and social pharmacy. Consideration was given to how, when and if these elements interacted and contributed to the movement toward pharmaceutical care. RESULTS: During the early years of the 20th century the professional role of the pharmacist, based on preparing medications, declined because of the increased industrial production of drugs. In The Netherlands, a number of developments, starting around 1995, led to a "reprofessionalization" movement in pharmacy, characterized by pharmacists' increased awareness of social and ethical responsibilities with respect to drugs and patients. These developments included an improved relationship between pharmacists and physicians, the implementation of clinical pharmacy and medical surveillance in daily community pharmacy practice in the 1970s and 1980s, and the increased awareness of the rights of patients to quality drug information and counseling in the 1980s and 1990s. By the end of 1980 these trends had coalesced into a professional movement supporting the need for a pharmaceutical care model of practice. CONCLUSION: Dutch pharmacy is gradually implementing pharmaceutical care in daily community practice. However, a proactive attitude, not only from the "front runners," but from all pharmacists, is desirable if pharmaceutical care is to be incorporated into routine community practice.

History, 20th Century↗
PubMedDate not supplied

Albatros: an innovative low-cost wheelchair.

A low-cost, comfortable, attractive and ergonomically optimized wheelchair, aimed at the Third-World population, was designed and built. It was field tested and the prototype modified accordingly.

Equipment Design↗