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Biomedical subjects

A Verhoeven

Publications and source records attributed to A Verhoeven.

17 recordsLinked to original sources

Early and aggressive treatment of rheumatoid arthritis patients affects the association of HLA class II antigens with progression of joint damage.

OBJECTIVE: The presence of certain HLA class II antigens is strongly associated with the progression of joint destruction in rheumatoid arthritis (RA). Such antigens may be more effective than other class II antigens in inducing the formation of autoreactive T cells after presentation of (auto)antigens. We investigated whether early and aggressive treatment with disease-modifying antirheumatic drugs could modify this relationship. METHODS: We analyzed data from 2 studies of patients with early RA treated according to different strategies. The first study consisted of 2 cohorts, one (n = 109; median disease duration before treatment 4 months) was treated according to the pyramid strategy (initial nonsteroidal antiinflammatory drugs, followed by chloroquine [CQ] or sulfasalazine [SSZ] when necessary), and the other (n = 97; median disease duration before treatment 2 weeks) was immediately treated with CQ or SSZ. The second study comprised 155 patients (median disease duration 4 months) from the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial, in which patients were randomly assigned to combination treatment with step-down prednisolone, methotrexate (MTX), and SSZ (n = 76) or with SSZ alone (n = 79). Prednisolone and MTX dosages were tapered and stopped after 28 and 40 weeks, respectively. The extent of joint damage was measured by the modified Sharp method. RESULTS: In the pyramid treatment cohort, the median increase in Sharp score after 2 years was 12 in patients positive for the shared epitope (SE) and 1 in SE- patients. In the immediate treatment cohort, the median increase was 3 in SE+ patients and 2 in SE- patients. In the SSZ group of the COBRA study, the median increase in Sharp score after 1 year was 11 in DR4+ patients and 3 in DR4- patients. In the combination treatment group, the median increase was 4 in DR4+ patients and 2 in DR4- patients. Significance was confirmed by multiple regression using log-transformed scores. CONCLUSION: Early and aggressive antirheumatic drug treatment affects the association of HLA class II alleles with progression of joint damage in RA.

Adult↗

Rheumatoid factor measured by fluoroimmunoassay: a responsive measure of rheumatoid arthritis disease activity that is associated with joint damage.

OBJECTIVES: To determine whether rheumatoid factors (RFs), measured as continuous variables by time resolved fluoroimmunoassay, reflect disease activity in rheumatoid arthritis (RA). Further, to study the association of RFs and other disease activity parameters with radiological joint damage, especially in individual patients. METHODS: In active, early RA, IgM and IgA RFs, as well as erythrocyte sedimentation rate (ESR), C reactive protein (CRP), tender joint score, and swollen joint score were assessed regularly. At the study start and at 56 and 80 weeks, radiographs of hands and feet were assessed by the Sharp score (van der Heijde modification). Associations between RFs and disease activity parameters were studied. In addition, associations between radiographic damage and disease activity parameters (baseline and time integrated) were analysed by non-parametric tests and multiple regression analysis. The relation between time integrated disease activity parameters and radiological damage in individual patients was analysed and visualised. RESULTS: 155 patients were included. RF levels were strongly associated with the disease activity parameters (especially ESR and CRP) and with each other. All disease activity parameters, at baseline as well as time integrated parameters, were associated with (the progression of) radiographic damage. Moreover, in individual patients, a linear relationship between time integrated disease activity parameters and progression of radiological damage was seen. CONCLUSION: RFs, measured as continuous variables, can be considered as disease activity parameters in patients with RA. The level of RF at baseline and the exposure to RF over time is associated with radiological damage. In individual patients, there is a constant relation between disease activity and radiological damage.

Arthritis, Rheumatoid↗

The Cunningham Fellowship: three international points of view.

The Medical Library Association Cunningham Fellowship Program provides funds for one medical librarian per year from outside the United States or Canada to work and learn in United States or Canadian medical libraries for a period of 4 months. An overview of the Cunningham Fellowship is presented from three different points of view-that of a Medical Library Association member who has worked closely with the Cunningham Fellowship programme, and two former Cunningham Fellows. Anita Verhoeven, who relates her impressions of American culture, architecture and art, was the 1998 MLA Cunningham Fellow and visited 33 libraries, met 171 librarians, visited prestigious universities and attended a Medical Library Association meeting. Ioana Robu, the 1997 Cunningham Fellow, visited 15 libraries in 13 cities during her experience. She describes the process of applying for the fellowship and assesses the impact that the 1997 Cunningham Fellowship has made on her life, her library and medical librarianship in Romania. An overview of the Cunningham Fellowship is also given, which includes the history, the application process, the requirements of the fellowship and the time table of the fellowship.

Fellowships and Scholarships↗

Robustness and generalizability of smallest detectable difference in radiological progression.

The smallest detectable difference (SDD) reflects that component of a measure statistically attributable to error from the measurement process itself. As such it is an irreducible component of the inherent variability in measurements in clinical trials and will affect their design, whether randomized or observational. Even though the application of the SDD concept to assaying radiographs in rheumatoid arthritis is relatively new and not well understood, systematic work on the influences of radiographic SDD can be done. This report describes the effects of a number of clinical aspects of the disease and operational aspects of trials on the values of the SDD of radiographic progression data. We show that if conditions affecting SDD are known and kept constant across datasets, the SDD of radiological progression from one study may be generalizable to other studies. However, if any one condition varies, the SDD is distinctly unrobust and cannot be generalized to other studies.

Arthritis, Rheumatoid↗

Factors determining the place of palliative care and death of cancer patients.

Factors determining the place of palliative care and death were studied by interviewing 40 patients using a semi-structured questionnaire. The 86 interviews assessed showed that both emotional and somatic factors played a part in the determination of whether patients were transferred and of their place of death. Emotional factors were mentioned in 41% as being of importance, and physical factors in 32%. Material and financial factors are probably underestimated owing to the methodology.

Adult↗

High-speed magic-angle spinning 13C MAS NMR spectra of adamantane: self-decoupling of the heteronuclear scalar interaction and proton spin diffusion.

We have investigated the carbon line shape of solid adamantane under high-speed magic-angle sample spinning (MAS) acquired without proton decoupling. The CH-group shows a spinning-speed-dependent line broadening while the CH2-group consists of a spinning-speed-independent sharp component and a spinning-speed-dependent broader part. These phenomena can be explained by self-decoupling of the J-interaction due to proton spin diffusion. Such a self-decoupling process can be described by a magnetization exchange process between the multiplet lines. Changing the spin-diffusion rate constant by off-resonance irradiation of the protons allows us to observe the full range from slow exchange to coalescence to fast exchange of the carbon spectra. One of the multiplet components in the CH2-group corresponds to a group spin of the protons of zero and therefore does not couple to the other protons. This gives rise to the sharp central line. The magnetization exchange rate constant between the different multiplet lines can be determined from the spectra and is a measure for the spinning-speed-dependent proton spin-diffusion rate constant. Even at an MAS speed of 30 kHz, proton spin diffusion is still observable despite the relatively weak intermolecular proton dipolar-coupling network in adamantane which results in a static proton line width of only 14 kHz (full width at half height).

Adamantane↗

Induction of the oxidative catabolism of retinoid acid in MCF-7 cells.

Cytochrome P450-dependent oxidation is a pathway for all-trans-retinoic acid (all-trans-RA) catabolism. Induction of this catabolic pathway was studied in MCF-7 breast cancer cells. MCF-7 cells showed low constitutive all-trans-RA catabolism. Concentration-dependent induction was obtained by preincubation of the cells with all-trans-RA (10(-9) to 10(-6) M). Onset of induction was fast, being detectable within 60 min, with maximal induction (45-fold) obtained after 16 h. Enzymatic characterization of induced all-trans-RA catabolism showed an estimated Km value (Michaelis-Menten constant) of 0.33 microM and a Vmax value (maximal velocity of an enzyme-catalysed reaction) of 54.5 fmol polar all-trans-RA metabolites 10(6) cells(-1) h(-1). These kinetic parameters represent the overall formation of polar metabolites from all-trans-RA. Induction of all-trans-RA catabolism was also obtained with other retinoids, CH55 >> 13-cis-RA = all-trans-RA > 9-cis-RA > 4-keto-all-trans-RA > 4-keto-13-cis-RA > retinol. The potency of the retinoids to induce all-trans-RA catabolism was correlated to their retinoic acid receptor affinity (Crettaz et al, 1990; Repa et al, 1990; Sani et al, 1990). Induction of all-trans-RA catabolism was inhibited by actinomycin D. Furthermore, all-trans-RA did not increase cytosolic retinoic acid-binding protein (CRABP) mRNA levels. These data suggest that induction of all-trans-RA catabolism in MCF-7 cells is a retinoic acid receptor-mediated gene transcriptional event. Induced all-trans-RA catabolism was inhibited by various retinoids with decreasing potency in the order: all-trans-RA > 4-keto-all-trans-RA > 13-cis-RA > 9-cis-RA > 4-keto-13-cis-RA > retinol > CH55. The antitumoral compound liarozole-fumarate inhibited all-trans-RA catabolism with a potency similar to that of all-trans-RA.

Antineoplastic Agents, Hormonal↗

Mechanisms involved in receptor-mediated changes of intracellular Ca2+ in liver.

Interactions between the different signaling roles of myo-inositol 1,4,5-trisphosphate and 1,2-diacylglycerol, the products of agonist-stimulated phosphatidylinositol 4,5-bisphosphate breakdown, are assessed in isolated rat hepatocytes. Measurements of the kinetics of accumulation of individual [3H]inositol phosphates after the addition of different Ca2+-mobilizing agonists in general support the role of inositol 1,4,5-trisphosphate as the second messenger responsible for release of sequestered intracellular Ca2+. Various agonists, when added at maximal concentrations, however, produce qualitatively and quantitatively different responses, which reflect varying abilities of the agonists to activate phospholipase C. Qualitative differences are revealed by a pronounced biphasic pattern to the Ins(1,4,5)P3 accumulation after vasopressin and phenylephrine stimulation, which is indicative of negative feedback. It is suggested that this effect is mediated by a partial diacylglycerol activation of protein kinase C, which in vitro causes an activation of inositol phosphate 5-phosphatase and hence promotes removal of Ins(1,4,5)P3 to Ins(1,4)P2. An alternative mechanism proposed by Biden and Wollheim (1986) of a secondary Ca2+ activation of Ins(1,4,5)P3 3-kinase is considered less likely as a general mechanism, since highly purified kinase prepared from rat brain shows only an inhibition by Ca2+. Glucagon, 8-Br-cAMP, and EGF induce small increases of Ins(1,4,5)P3 in hepatocytes, together with slower and smaller increases of cytosolic free Ca2+ than those produced by vasopressin or phenylephrine, with Ca2+ being mobilized from the same intracellular pools with each of the agonists. The Ca2+-mobilizing effect of glucagon, therefore, may be entirely due to a cAMP-dependent process, although a direct receptor-mediated activation of phospholipase C, as suggested by Wakelam et al. (1986), remains a possibility. The EGF receptor appears to be coupled to phospholipase C, presumably via a G-protein. It is speculated that the mechanism by which cAMP increases Ins(1,4,5)P3 levels in hepatocytes could either be by phosphorylation and inhibition of inositol phosphate 5-phosphatase or by phosphorylation and facilitation of the coupling between the G-protein and phospholipase C. When protein kinase C is maximally activated by pretreatment of hepatocytes with PMA, the stimulatory effects of phenylephrine, glucagon, 8-Br-cAMP, and EGF on the accumulation of inositol phosphates and increase of cytosolic free Ca2+ are largely inhibited.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Blood gas and hemodynamic changes induced by the treatment of pulmonary congestion with vasodilators in the acute phase of myocardial infarction.

The effects of vasodilators on hemodynamics and blood gases was assessed in 31 patients suffering from acute myocardial infarction (AMI) who had clinical signs of left ventricular failure with high pulmonary wedge pressure (PWP greater than 15 mm Hg). Molsidomine (n = 10), phentolamine (n = 12) and sulmazol (n = 9) were administered intravenously to decrease the PWP by 20%. Molsidomine significantly decreased PWP after one hour with a mild increase in cardiac index (CI) inducing a slight decrease in paO2 (64 to 59 mm Hg, P less than 0.1) with no change in p-vO2. Phentolamine and Sulmazol significantly increased the CI and decreased the PWP, with a substantial increase in the pv-O2 (28 to 32 mm Hg, P less than 0.005 and 28 to 31 mm Hg, P less than 0.001) and no significant change in the paO2 (60 to 65 mm Hg, P less than 0.1 and 68 to 69 mm Hg, NS). None of these drugs significantly changes the pulmonary vascular resistance (PVR) which would explain the lack of any significant change in paO2. The treatment of pulmonary congestion in AMI by either pure venous (molsidomine) or arteriolar and venous (phentolamine and sulmazol) vasodilators does not worsen obviously pre-existant hypoxemia.

Adult↗

The role of eIF-4C in protein synthesis initiation complex formation.

eIF-4C has a pronounced stimulatory effect on initiation complex formation with native 80-S ribosomes (80-Sn) as the only source of ribosomal subunits, but only a small effect when washed 40-S subunits are used. eIF-4C is accessary to eIF-3 in dissociating 80-Sn ribosomes. eIF-4C is present on 40-Sn but absent on 40-Sn dimers, which occur in preparations of native ribosomes and are as such inactive in protein synthesis. eIF-4C dissociates 40-Sn dimers into active monomers. These results can be explained by assuming that the presence of eIF-4C on 40-Sn prevents: (a) premature association with 60-S ribosomal subunits and (b) dimerisation, thus increasing the rate and extent of initiation complex formation.

Animals↗