PubMed Health⌕ Search

Biomedical subjects

C de Vries

Publications and source records attributed to C de Vries.

At least 19 recordsLinked to original sources
PubMed2006

Spontaneous superficial venous thrombophlebitis: does it increase risk for thromboembolism? A historic follow-up study in primary care.

OBJECTIVE: To determine the risk of arterial and venous complications after a spontaneous superficial venous thrombophlebitis (SVTP) in the leg in a general practice population. STUDY DESIGN: Retrospective cohort study (LOE: 2b [CEBM]). Exposure consisted of the diagnosis of SVTP of the lower limbs on an index date. The exposed cohort was compared with an (unexposed) cohort of practice-, age-, and sex-matched controls without SVTP. POPULATION: Patients with spontaneous SVTP in the leg were identified through diagnostic coding in the medical registers of 40,013 patients, enlisted with 5 health centers in Amsterdam, The Netherlands. OUTCOMES: Primary outcomes were deep venous thrombosis (DVT), pulmonary embolism (PE), acute coronary events, or ischemic stroke over a 6-month follow-up period. Odds ratios (OR) were used to quantify the associations between SVTP and outcome events. RESULTS: No statistically significant odds ratios were found for PE, coronary events or stroke. DVT was the only primary outcome to show a significant relationship. DVT occurred in 2.7% of all SVTP patients as compared with 0.2% in the controls (OR=10.2; 95% confidence interval [CI], 2.0-51.6). When controlling for prior history of DVT, the OR decreased to 7.1 and the confidence interval crossed 1.0 (95% CI, 0.9-65.6). DISCUSSION: Spontaneous SVTP in the leg is a risk factor for DVT, but is less predictive in patients with prior DVT. Although effective treatments for the prevention of DVT are available, the absolute risk is too low to advocate prophylaxis in a general practice population. More research on prophylaxis is needed to stratify these patients at risk.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Uterine artery embolization for symptomatic fibroids.

OBJECTIVES: The aim of this study was to introduce uterine artery embolization (UAE) as an effective and safe treatment option in patients with symptomatic fibroids. METHODS: Sixty-one patients underwent UAE with a 3- and 12-month follow-up. RESULTS: The procedure was well tolerated in all patients with the following symptoms improving: heavy bleeding [90% (95% CI 80.21%; 95.4%)]; dysmenorrhea [median -4 (95% CI -5; -4)]; feeling of a mass [74% (95% CI 57.9%; 85.8%)]; abdomino-pelvic discomfort [88% (95% CI 75.5%; 94.9%)]; and deep dyspareunia [90% (95% CI 71.1%; 97.3%)]. Uterine volume decreased by a median difference of 188 cm(3) (95% CI 146.5; 236), which related to a median % reduction of 37.7% (95% CI 32.4%; 45%) at 12-month follow-up. Most (91%) patients were satisfied with the procedure and only minor complications occurred. CONCLUSIONS: Uterine artery embolization can be performed effectively and safely at centers with the necessary expertise and can be used with success in Africa.

Adult↗
PubMed2004

Uterine artery embolisation for symptomatic fibroids: the effect of the large uterus on outcome.

OBJECTIVE: The aim of this study was to evaluate the efficacy of uterine artery embolisation (UAE) in myomatous uteri larger than 24 week's gestation (780 cm3). DESIGN: Prospective case control study. SETTING: Universitas Hospital, University of the Free State, Bloemfontein, South Africa. POPULATION: Sixty-one women, who underwent UAE, were included in the study. The study group comprised of 12 women with uteri > or =780 cm3 and the control group 49 women with uteri <780 cm3. METHODS: UAE was performed and the difference in outcome for the two groups was determined at 12 months. MAIN OUTCOME MEASURE: Symptomatic improvement with embolisation of the large uterus. RESULTS: Reduction of dysmenorrhoea, menorrhagia and pressure effects was similar for both groups. The median reduction in uterine volume (pre- to post-embolisation) was 188 cm3 (range 28-2038 cm3) with a 95% CI for the median difference for paired data of 146.5 and 236. Only 66% of the study group had, however, a reduction in volume to <780 cm3. The complication rates were similar for the two groups with regards to post-embolisation syndrome, fibroid slough, haematoma formation, infection, hysterectomy and failure to embolise. Satisfaction was similar between the two groups, with 91% of women satisfied with the procedure. CONCLUSION: The large uterus does not decrease UAE's efficacy. Although 33.3% of the study group still had a uterus of > or =780 cm3, symptom reduction was still similar for both groups. Women may thus still be left with a large uterine volume but without symptoms. This must be taken into consideration when counselling women with an extremely large uterus for UAE.

Adult↗
PubMed2001

Prednisolone does not prevent hypersensitivity reactions in antiretroviral drug regimens containing abacavir with or without nevirapine.

OBJECTIVES: To determine the effect of adjuvant prednisolone use on the development of abacavir (ABC)- and nevirapine (NVP)-associated hypersensitivity reactions (HSR). METHODS: Randomized open-label study in antiretroviral-naive adult HIV-1 infected patients using a factorial design in which NVP and/or hydroxyurea (HU) and/or prednisolone are added to a regimen of ABC, zidovudine and lamivudine. Prednisolone (40 mg once daily) was added for the first 2 weeks of treatment. As it was difficult to distinguish ABC-associated HSR from NVP-associated HSR, these events were treated as a composite endpoint. The odds ratio (OR) of developing HSR for prednisolone-use was calculated with and without stratification by NVP and/or HU. Logistic regression was performed to identify risk factors for developing HSR. RESULTS: Of the 229 patients 115 were randomized to prednisolone and 114 to no-prednisolone; 19 (17%) and 11 (10%) patients, respectively, developed HSR. The expected prevention of HSR by prednisolone use was not observed. In fact use of prednisolone showed an increased risk for HSR although this did not reach statistical significance [OR, 1.82; 95% confidence interval (CI), 0.82-4.03]. There was a higher incidence of HSR in the NVP group than in the non-NVP group (20% versus 6%; P = 0.002). An additional risk factor identified in a multivariate logistic model was a high baseline CD4 cell count (OR, 1.26 per 100 x 10(6) cells/l increase; 95% CI, 1.06-1.51). CONCLUSIONS: The simultaneous start of ABC and NVP in first-line antiretroviral regimens should be avoided because of a high (20%) incidence of HSR. Short-term therapy with prednisolone did not prevent HSR in patients using ABC with or without NVP.

Adult↗
PubMed1999

Possible role for ligand binding of histidine 81 in the second transmembrane domain of the rat prostaglandin F2alpha receptor.

For the five principal prostanoids PGD2, PGE2, PGF2alpha, prostacyclin and thromboxane A2 eight receptors have been identified that belong to the family of G-protein-coupled receptors. They display an overall homology of merely 30%. However, single amino acids in the transmembrane domains such as an Arg in the seventh transmembrane domain are highly conserved. This Arg has been identified as part of the ligand binding pocket. It interacts with the carboxyl group of the prostanoid. The aim of the current study was to analyze the potential role in ligand binding of His-81 in the second transmembrane domain of the rat PGF2alpha receptor, which is conserved among all PGF2alpha receptors from different species. Molecular modeling suggested that this residue is located in close proximity to the ligand binding pocket Arg 291 in the 7th transmembrane domain. The His81 (H) was exchanged by site-directed mutagenesis to Gln (Q), Asp (D), Arg (R), Ala (A) and Gly (G). The receptor molecules were N-terminally extended by a Flag epitope for immunological detection. All mutant proteins were expressed at levels between 50% and 80% of the wild type construct. The H81Q and H81D receptor bound PGF2alpha with 2-fold and 25-fold lower affinity, respectively, than the wild type receptor. Membranes of cells expressing the H81R, H81A or H81G mutants did not bind significant amounts of PGF2alpha. Wild type receptor and H81Q showed a shallow pH optimum for PGF2alpha binding around pH 5.5 with almost no reduction of binding at higher pH. In contrast the H81D mutant bound PGF2alpha with a sharp optimum at pH 4.5, a pH at which the Asp side chain is partially undissociated and may serve as a hydrogen bond donor as do His and Gln at higher pH values. The data indicate that the His-81 in the second transmembrane domain of the PGF2alpha receptor in concert with Arg-291 in the seventh transmembrane domain may be involved in ligand binding, most likely not by ionic interaction with the prostaglandin's carboxyl group but rather as a hydrogen bond donor.

Amino Acid Substitution↗
PubMed1998

Cytokines and soluble adhesion molecules in sickle cell anemia patients during hydroxyurea therapy.

Hydroxyurea (HU) induces HbF production and can reduce painful crises in some patients with sickle cell anemia (SS). However, HbF induction alone cannot explain the beneficial effect of HU treatment as some patients experience clinical improvement while showing only minor increases in HbF. Other actions of HU, in particular its effects on vascular endothelium, adhesion molecule expression and cytokine production may also play a role in the final therapeutic outcome. In order to analyze these effects we studied the levels of interleukin-3 (IL-3), interleukin-6, granulocyte-macrophage colony-stimulating factor, erythropoietin, stem cell factor, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule-1, soluble E-selectin and soluble P-selectin in 7 SS patients before and during 5 months of HU treatment. Use of HU seems to have no detectable effect on soluble adhesion molecules, but the steady state levels of soluble vascular adhesion molecule-1 are enhanced in SS patients compared to normal controls. Of the cytokines studied, only IL-3 showed an increase during therapy, suggesting HU may induce early erythroid progenitors capable of producing HbF by a direct or indirect effect on IL-3 production. Remarkably, the steady state stem cell factor levels in sickle cell patients seemed to be decreased compared to healthy controls.

Adult↗
PubMed1995

Remote expert consultation for MRI procedures by means of teleradiology.

From April 1992 to January 1993, radiology expert opinion for MRI procedures was offered by means of teleradiology. The experiment was carried out in addition to an existing service of a mobile MRI unit. MRI images were sent by means of teleradiology via regular telephone lines from the mobile MRI unit to an academic hospital, which served as expert consultation centre. During this period, 43 requests for expert opinions were performed. This article describes the clinical effects of these expert opinions, and the technical and organisational requirements to perform teleradiology in daily clinical practice.

Humans↗
PubMed1994

The specific roles of finger and kringle 2 domains of tissue-type plasminogen activator during in vitro fibrinolysis.

The specific roles of the finger (F) and kringle 2 (K2) domains of tissue-type plasminogen activator (t-PA) were quantified with regard to fibrin binding and kinetic parameters for plasminogen activation by employing domain-deletion variants. On an intact fibrin clot, active site-blocked 125I-t-PA has a dissociation constant (Kd) of 0.36 +/- 0.08 microM and a single binding site per fibrin monomer (n = 1.1 +/- 0.1). Deletion of the K2 domain results in a 3-fold increase of the Kd (1.1 +/- 0.2 microM) and a 2-fold increase of the binding sites per fibrin monomer (n = 2.0 +/- 0.3). Deletion of the F domain results in nonsaturable binding with high Kd (3.2 +/- 0.6 microM). These results indicate that the high affinity binding of t-PA to intact fibrin is the resultant of the cooperation of two low affinity binding sites assembled on intact t-PA. Furthermore, fibrin clot lysis experiments were performed, using polymerized fibrin and plasminogen. Enzymatic activity of t-PA (variants) was assessed by following the decrease in turbidity of the polymerized fibrin. Intact recombinant t-PA exhibited a Michaelis constant for plasminogen activation (Km) of 37 +/- 2 nM. Deletion of either the K2 or F domain results in an increase of the Km for plasminogen of 4- and 16-fold, respectively. We interpret these kinetic parameters in terms of the ternary complex model: binding of t-PA to fibrin, mediated simultaneously by both the F and K2 domain, is essential for a correct orientation of the enzyme on the fibrin polymer to yield the optimal "Km-driven" stimulation of fibrin on the activation of plasminogen. The different potencies of various deletion mutants in a plasma clot are explained by decreased affinity of the enzymes both for fibrin and for the substrate plasminogen.

Binding Sites↗
PubMed1993

Initial and long-term results of coronary angioplasty and coronary bypass surgery in patients of 75 or older.

OBJECTIVE--To evaluate clinical outcome after percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) in patients of 75 or older who underwent either procedure between 1980 and 1987. SUBJECTS--93 patients aged 75-89 with angina pectoris class III-IV (Canadian Cardiovascular Society) who underwent PTCA and 81 patients aged 75-84 with angina class III-IV who underwent CABG. Follow up was 8.2 years in the PTCA group and 8.3 years in the CABG group. MAIN OUTCOME MEASURES--In-hospital complications and survival at follow up. RESULTS--Primary success rate for PTCA was 84% (78/93). Two patients died, two had emergency CABG, three had a myocardial infarction, and one had a cerebrovascular accident. PTCA failed in seven patients (five underwent elective CABG and two were treated conservatively). Median hospital stay was 4.3 days. Primary success rate for CABG was 63% (53/81). Six patients died, two had a cerebrovascular accident, eight had a myocardial infarction, 10 had a rethoracotomy, and four the adult respiratory distress syndrome. Median hospital stay was 14.2 days. In the PTCA group during follow up eight patients died, three had a non-fatal myocardial infarction, two had elective CABG, 10 had repeat PTCA, and four had recurrence of angina. Sixty four patients were free of angina (69%). In the CABG group during follow up eight patients died, one had a non-fatal myocardial infarction, six had PTCA, and three had recurrence of angina. Fifty seven patients were free of angina AP (70%). Actuarial survival after 10 years was 92% for PTCA and 91% for CABG. CONCLUSIONS--PTCA is safe in elderly patients. The complication rate is lower and hospital stay significantly shorter compared with CABG (p < 0.05). Long-term follow up showed no significant difference between PTCA and CABG.

Aged↗
PubMed1992

The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor.

The fms-like tyrosine kinase (Flt) is a transmembrane receptor in the tyrosine kinase family. Expression of flt complementary DNA in COS cells conferred specific, high-affinity binding of vascular endothelial growth factor, also known as vascular permeability factor (VEGF-VPF), a factor that induces vascular permeability when injected in the guinea pig skin and stimulates endothelial cell proliferation. Expression of Flt in Xenopus laevis oocytes caused the oocytes to release calcium in response to VEGF-VPF. These findings show that flt encodes a receptor for VEGF-VPF.

Animals↗
PubMed1992

Differential splicing in the extracellular region of fibroblast growth factor receptor 1 generates receptor variants with different ligand-binding specificities.

We have cloned a genomic region of the murine fibroblast growth factor (FGF) receptor 1 (FGFR1) gene that includes three alternative exons for the third immunoglobulinlike domain in the extracellular region of the receptor. The mRNA of one of these splice variants encodes a secreted receptor that lacks transmembrane and cytoplasmic sequences as well as a portion of the third immunoglobulinlike domain. Highest levels of mRNA encoding this variant were found in brain, skeletal muscle, and skin. We expressed this form of FGFR1 in CHO cells and showed that the recombinant secreted protein binds acidic FGF. We also discovered a novel alternative exon in the third immunoglobulinlike domain that encodes part of a transmembrane FGFR1 mRNA. This exon is highly homologous to the corresponding region of the keratinocyte growth factor receptor. Transcripts including this exon were present at highest levels in the skin. We cloned an FGFR1 cDNA which includes this exon and expressed this receptor variant in L6 rat skeletal muscle myoblasts. The new receptor variant had a 50-fold-lower affinity for basic FGF than does the published FGFR1 variant, whereas both forms of receptor bound acidic FGF with high affinity. These results show that the third immunoglobulinlike domain plays an important role in determining the binding specificities for different FGFs. Our data provide the first evidence that differential splicing in the extracellular region of a receptor gene generates receptor variants with different ligand-binding specificities.

Amino Acid Sequence↗
PubMed1991

Phosphorylation of nuclear protein is an early event in TGF beta 1 action.

Transforming growth factor beta (TGF beta) is a family of polypeptides that modulate growth and differentiation. TGF beta exerts its effects on target cells through interaction with specific cell surface receptors, but the signal transduction pathways are as yet largely unresolved. In this study we report that the growth inhibitory action of TGF beta on mink lung CCl 64 cells is associated with a rapid and transient phosphorylation of a number of nuclear proteins. In parallel, a transient expression of the immediate early gene jun B is observed. The expression of jun B can be inhibited by the protein kinase inhibitor H7 and can be augmented by the phosphatase inhibitor okadaic acid. Thus, protein phosphorylation can be a possible mechanism through which TGF beta 1 initiates early genomic responses.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Kinetic characterization of tissue-type plasminogen activator (t-PA) and t-PA deletion mutants.

The binding of t-PA to fibrin is mediated both by its "finger" (F) and its "kringle 2" (K2) domain. In addition, these domains are involved in the stimulation of t-PA activity by fibrin. We analyzed the kinetic characteristics of Glu-plasminogen activation by t-PA and a set of t-PA deletion mutants in the absence and the presence of desA-fibrin. In the absence of desA-fibrin, the activity of t-PA (variants) is determined by the presence of the protease domain, irrespective of the composition of the amino-terminal heavy chain. In the presence of the cofactor desA-fibrin, the activity of t-PA (variants) is dependent on the domain composition of the heavy chain. The activity of t-PA is stimulated 2,400 fold by desA-fibrin, whereas the activity of the mutant lacking the K1 domain (del. K1) increases 936 fold in the presence of this cofactor. Mutants lacking either the K2 domain (del. K2) or the F domain (del. F) exhibit an enhanced activity upon desA-fibrin addition of 200 and 210 fold, respectively. DesA-fibrin has no stimulatory effect on the activity of the mutant containing only the serine-protease domain (del.FE K1 K2) nor on the activity of the variant containing only the K1 domain and the serine-protease domain (del. FE K2). Furthermore, we determined the relative fibrin affinity of each t-PA variant, which is similarly dictated by the composition of the heavy chain.

Amino Acid Sequence↗
PubMed1991

Fibronectin decreases the stimulatory effect of fibrin and fibrinogen fragment FCB-2 on plasmin formation by tissue plasminogen activator.

Fibronectin is a dimeric glycoprotein (Mr 440,000) involved in many adhesive processes. During blood coagulation it is bound and cross-linked to fibrin. Fibrin binding is achieved by structures (type I repeats) which are homologous to the "finger" domain of tissue plasminogen activator. Tissue plasminogen activator also binds to fibrin via the finger domain and additionally via the "kringle 2" domain. Fibrin binding of tissue plasminogen activator results in stimulation of its activity and plays a crucial role in fibrinolysis. Since fibronectin might interfere with this binding, we studied the effect of fibronectin on plasmin formation by tissue plasminogen activator. In the absence of fibrin, fibronectin had no effect on plasminogen activation. In the presence of stimulating fibrinogen fragment FCB-2, fibronectin increased the duration of the initial lag phase (= time period until maximally stimulated plasmin formation occurs) and decreased the rate of maximal plasmin formation which occurs after that lag phase mainly by increasing the Michaelis constant (Km). These effects of fibronectin were dose-dependent and were similar with single- and two-chain tissue plasminogen activator. They were also observed with plasmin-pretreated FCB-2. An apparent Ki of 43 micrograms/ml was calculated for the inhibitory effect of fibronectin when plasminogen activation by recombinant single-chain tissue plasminogen activator was studied in the presence of 91 micrograms/ml FCB-2. When a recombinant tissue plasminogen activator mutant lacking the finger domain was used in a system containing FCB-2, no effect of fibronectin was seen, indicating that the inhibitory effect of fibronectin might in fact be due to competition of fibronectin and tissue plasminogen activator for binding to fibrin(ogen) via the finger domain.

Fibrin↗
PubMed1990

Tissue-type plasminogen activator and its substrate Glu-plasminogen share common binding sites in limited plasmin-digested fibrin.

The enzyme tissue-type plasminogen activator (t-PA) and its substrate Glu-plasminogen can both bind to fibrin. The assembly of these three components results in about a 1000-fold acceleration of the conversion of Glu-plasminogen into plasmin. Fibrin binding of t-PA is mediated both by its finger (F) domain and its kringle-2 domain. Fibrin binding of Glu-plasminogen involves its kringle structures (K1-K5). It has been suggested that particular kringles contain lysine-binding sites and/or aminohexyl-binding sites, exhibiting affinity for specific carboxyl-terminal lysines and intrachain lysines, respectively. We investigated the possibility that t-PA and Glu-plasminogen kringles share common binding sites in fibrin, limitedly digested with plasmin. For that purpose we performed competition experiments, using conditions that exclude plasmin formation, with Glu-plasminogen and either t-PA or two deletion mutants, lacking the F domain (t-PA del.F) or lacking the K2 domain (t-PA del.K2). Our data show that fibrin binding of t-PA, mediated by the F domain, is independent of Glu-plasminogen binding. In contrast, partial inhibition by Glu-plasminogen of t-PA K2 domain-mediated fibrin binding is observed that is dependent on carboxyl-terminal lysines, exposed in fibrin upon limited plasmin digestion. Half-maximal competition of fibrin binding of both t-PA and t-PA del.F is obtained at 3.3 microM Glu-plasminogen. The difference between this value and the apparent dissociation constant of Glu-plasminogen binding to limitedly digested fibrin (12.1 microM) under these conditions is attributed to multiple, simultaneous interactions, each having a separate affinity. It is concluded that t-PA and Glu-plasminogen can bind to the same carboxyl-terminal lysines in limitedly digested fibrin, whereas binding sites composed of intrachain lysines are unique both for the K2 domain of t-PA and the Glu-plasminogen kringles.

Binding Sites↗