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Biomedical subjects

P Verdonk

Publications and source records attributed to P Verdonk.

17 recordsLinked to original sources

Cyclodextrin polysulphates repress IL-1 and promote the accumulation of chondrocyte extracellular matrix.

OBJECTIVE: To evaluate the influence of cyclodextrin polysulphate (CDPS) on the extracellular matrix (ECM) metabolism of human articular cartilage chondrocytes. METHODS: Isolated chondrocytes from femoral condyle cartilage of human knee joints were cultured in gelled alginate to maintain their differentiated phenotype. During 1 week of culture, the cells were exposed to different concentrations of CDPS. Synthesis of aggrecans was investigated in these cultures after using Na(2)(35)SO(4) as a radioactive precursor during the last 24h of culture. The artificial matrix was then solubilised with Na-citrate and newly synthesised aggrecan aggregates, accumulated during culture, were liberated and assayed. The isolated chondrocytes were labelled with antibodies against aggrecan and type II collagen to analyse the ECM molecules in the cell-associated matrix (CAM). Plasma membrane levels of receptors for insulin-like growth factor-1 (IGF-1RI) and for interleukin-1 (IL-1RI and IL-1RII), as well as levels of IGF-1, IL-1alpha and -beta were determined after the cells had been permeabilized and stained with the appropriate antibodies. The release of IL-6 in the culture media was used as a variable reflecting auto/paracrine IL-1 activity of the cells in different experimental conditions. RESULTS: CDPS significantly increased total (35)S-incorporation rates in ECM aggrecan. When compared with controls, CDPS-treated chondrocytes expressed significantly higher CAM aggrecan and type II collagen levels. As plasma membrane-bound IGFR1 and intracellular IGF-1 levels remained unchanged, this increase in accumulated CAM compounds may have resulted from suppressed catabolic activities by the chondrocytes in culture. CDPS-treated cells expressed significantly lower amounts of intracellular IL-1alpha and -beta levels. Plasma membrane-bound IL-1RI and decoy IL-1RII remained unchanged. beta-cyclodextrin-treated chondrocytes released significantly less IL-6 in the supernatant culture media. CONCLUSION: CDPS is a novel polysulfated polysaccharide showing cartilage structure modifying effects in vitro as it improves the synthesis of aggrecan and the accumulation of CAM macromolecules. This effect probably resulted in part from the downregulation of IL-1.

Aggrecans↗

Integrating gender into a basic medical curriculum.

INTRODUCTION: In 1998, gaps were found to exist in the basic medical curriculum of the Radboud University Nijmegen Medical Centre regarding health-related gender differences in terms of biological, psychological and social factors. After screening the curriculum for language, content and context, adjustments aimed at incorporating gender issues were proposed. The aim of this study was to evaluate those adjustments, as well as to investigate whether gender had been successfully incorporated into the basic medical curriculum, and to identify the factors that played a role in this. METHODS: The education material of 9 curricular blocks was re-evaluated and interviews were held with block co-ordinators. RESULTS: Since the beginning of the project, gender has increasingly been brought to the attention of the students. Various factors have played a role: concrete and directly executable content-oriented proposals for adjustment; adequate translation of gender differences into actual patient care; motivated block co-ordinators; the presence of a 'trigger person' in the faculty; incorporation into the existing education programme; the involvement of block co-ordinators in decision making, and the provision of practical support. DISCUSSION: Integrating gender into the basic medical curriculum has been largely successful. Block co-ordinators' personal recognition of the importance of gender in patient care greatly facilitated implementation. The evaluation stimulated the forming of new ideas. It is recommended that these factors and those mentioned above should be taken into consideration when integrating gender into other faculties.

Curriculum↗

Placenta percreta causing rupture of an unscarred uterus at the end of the first trimester of pregnancy: case report.

Reports on placenta percreta in early pregnancy leading to a spontaneous rupture of the uterus are rare. We report a case of this potentially life-threatening complication in the 14th week of pregnancy in an otherwise healthy woman who underwent a manual extraction of the placenta during a previous delivery but who had no history of severe pathology that could have potentially resulted in uterine damage. The occurrence of severe abdominal pain and the presence of a large quantity of free fluid in the abdomen necessitated an emergency laparotomy, revealing a haemoperitoneum due to rupture of the uterus, which was followed by a hysterectomy. This case demonstrates that in patients with a history of placenta accreta and subsequent manual extraction of the placenta, a close investigation of the uterine wall and placentation should be performed in the first trimester in order to anticipate a placenta percreta.

Abdominal Pain↗

Magnetic resonance imaging of cartilage and cartilage repair.

Magnetic resonance (MR) imaging of articular cartilage has assumed increased importance because of the prevalence of cartilage injury and degeneration, as well as the development of new surgical and pharmacological techniques to treat damaged cartilage. This article will review relevant aspects of the structure and biochemistry of cartilage that are important for understanding MR imaging of cartilage, describe optimal MR pulse sequences for its evaluation, and review the role of experimental quantitative MR techniques. These MR aspects are applied to clinical scenarios, including traumatic chondral injury, osteoarthritis, inflammatory arthritis, and cartilage repair procedures.

Arthritis, Rheumatoid↗

[Bio-artificial implants in orthopedics].

Aging of the population and thus of loadbearing cartilage produces a number of degenerative symptoms. At the knee, considerable macroscopic asymmetry of the joint underlies these degenerative changes, were it not for two menisci that somewhat neutralize this discongruency. Microscopically, cartilage is a structure within the knee joint that allows for low friction and congruent movement. Repetitive microtrauma rather than macrotrauma can affect its integrity. Both microscopically and macroscopically reconstruction of a cartilage-like structure is achieved through implantation of cultured cells or auto- and allografts either by minimally invasive or classical surgery, which theoretically could have a beneficial effect on the natural course of degeneration.

Aged↗

Homeostasis of the extracellular matrix of normal and osteoarthritic human articular cartilage chondrocytes in vitro.

OBJECTIVE: In normal articular cartilage cells, the IGFRI/insulin-like growth factor 1 (IGF-1) autocrine pathway was shown to overrule the catabolic effects of the IL-1/IL-1RI pathway by up-regulation of the IL-1RII decoy receptor. The activity of the IGF-1/IGFR1 and IL-1/IL-1R pathways, and of the IL-1RII control mechanism in the synthesis and turnover of the extracellular matrix (ECM) by chondrocytes from normal and osteoarthritic (OA) articular cartilage was compared in order to identify possible therapeutic targets of this disease. METHODS: Phenotypically stable human articular cartilage cells were obtained from normal and OA cartilage of the same knee showing focal OA. The cells were cultured in alginate beads over 1 week to re-establish the intracellular cytokine and growth factors, to reexpress the respective plasma membrane receptors and to reach equilibrium in accumulated cell-associated matrix (CAM) compounds. Following liberation of the cells from the alginate beads, the levels of cell-associated matrix (CAM) aggrecan, type II collagen and fibronectin, of intracellular IGF-1, IL-1alpha and beta and of their respective plasma membrane-bound receptors, IGFR1, IL-1RI and the decoy receptor IL-1RII, were assayed using flow cytometry. RESULTS: Coordinated production and accumulation of CAM aggrecan and type II collagen under the effect of the IGFR1/IGF-1 autocrine pathway-as documented for chondrocytes from healthy controls-was absent when the chondrocytes had been obtained from OA joints. When compared with cells obtained from normal tissues, chondrocytes from fibrillated OA cartilage expressed significantly higher intracellular IGF-1 levels and plasma membrane-bound IGFR1. At the same time, significantly higher intracellular IL-1alpha and beta levels and upregulated plasma membrane-bound IL-1RI were observed. Plasma membrane-bound IL-1RII decoy receptor was downregulated in OA chondrocytes. The levels of CAM aggrecan, type II collagen and fibronectin were significantly reduced in the chondrocytes obtained from pathological tissue. CONCLUSION: Paired analysis of normal and OA chondrocytes from the same knee joint has shown an enhanced capacity of chondrocytes from OA cartilage to produce ECM macromolecules. However, the same cells have increased catabolic signalling pathways. As a consequence of this increased IL-1 activity and the reduced amounts of IL-1RII decoy receptor, less of the produced ECM macromolecules may persist in the CAM of the OA chondrocytes.

Adult↗

Doppler ultrasound of the fetomaternal circulation: a preliminary study on differences between ethnic groups.

PURPOSE OF INVESTIGATION: The aim of this study was to investigate whether the same reference values might be used for the pulsatility index obtained by Doppler examinations of the fetal umbilical and middle cerebral artery and the maternal uterine arteries in autochthonous Belgian, Turkish and Moroccan women in Belgium. Notching of the uterine artery was also studied in the three ethnic groups. METHODS: Doppler measurements were performed in 206 autochthonous Belgian, 36 Moroccan and 36 Turkish pregnant women between 20 and 24 weeks gestational age for the umbilical artery, middle cerebral artery and uterine arteries. The mean uterine artery pulsatility index and the placentocerebral index were calculated. Intra-observer variation was calculated by repeat measurements on 20 videotaped examinations and intrapatient variation was determined by repeat examination in 60 patients. RESULTS: Maternal length was higher and body mass index lower in Belgian women; more of these admitted smoking during pregnancy. There were no statistically significant inter-ethnic differences for the pulsatility index of the umbilical artery, middle cerebral artery, placental-site uterine artery and the placentocerebral index. The pulsatility index in the non-placental-site uterine artery and the mean uterine artery was lower in the Moroccan group. Intra-patient variation expressed as intra-patient standard deviation of the umbilical and middle cerebral artery pulsatility index was relatively large compared to inter-patient variation, being 57% to 88% of the inter-patient standard deviation. This was not the case for the uterine artery. Notching of the uterine artery was not contributive for the prediction of intrauterine growth restriction or preeclampsia in these ethnic groups. CONCLUSION: Only small statistically significant differences were demonstrated. For clinical practice, the use of different reference charts for fetomaternal Doppler measurement in Belgian, Turkish and Moroccan women is not warranted.

Arteries↗

Fetal biometry in different ethnic groups.

OBJECTIVE: The aim of this study was to determine whether differences in ultrasound-measured fetal biometry exist between pregnant woman of autochthonous Belgian origin and migrant women from Morocco and Turkey. METHOD: A prospective cross-sectional study was performed in which fetal biparietal diameter, head circumference, abdominal circumference and femur length were measured in pregnant women presenting between 18 and 40 weeks of gestation. Fetal weight was calculated using the formulae by Shepard and Hadlock. Only uncomplicated singleton pregnancies with a certain date of the last menstrual period, confirmed by early ultrasound, were included. The father of the child had to be of the same ethnic origin as the mother. Polynomial regression of the different measurements was performed for women of autochthonous Belgian origin and for migrant women from Morocco and from Turkey. RESULTS: Singleton fetuses numbering 524 were examined, including 369 Belgian, 78 Moroccan and 77 Turkish. Polynomial regression was performed for the three groups for the biparietal diameter, head circumference, abdominal circumference, femur length and estimated fetal weight. No significant difference between the three different ethnic groups could be demonstrated for the biparietal diameter (P = 0.39). There was a significant difference for the head circumference (P = 0.017), the abdominal circumference (P = 0.0015), the femur length (P = 0.0014) and the estimated fetal weight for both formulae (Shepard P = 0.047; Hadlock P = 0.0006). CONCLUSION: In this set of cross-sectional data no significant difference for ultrasound-measured fetal biparietal diameter between autochthonous Belgian women and migrant women from Morocco and from Turkey could be demonstrated. Differences do exist for the head circumference, the abdominal circumference, the femur length and the estimated fetal weight. The use of adapted charts of fetal size for pregnant women of Turkish or Moroccan origin should be considered.

Belgium↗

Fetal binocular distance: no differences between ethnic groups.

OBJECTIVE: The aim of this study was to detect if interethnic differences for fetal binocular distance exist between the autochthonous Belgian population and immigrants from Turkey or Morocco, and to evaluate the need for different reference charts by ethnicity. METHODS: A prospective cross-sectional study was performed. In 246 pregnant women who presented for routine prenatal ultrasound between 18 and 40 weeks of gestation age the binocular distance was measured. Polynomial regression was performed for the three ethnic groups. RESULTS: The population consisted of 171 autochthonous Belgian women, 31 women from Turkish origin and 44 women from Moroccan origin. A statistically significant difference for the fetal binocular distance was noted between the Moroccan versus the autochthonous Belgian and Turkish fetuses (F test, p = 0. 047). The order of magnitude of this statistical difference is extremely small and does not result in clinical relevance. CONCLUSION: A small, but statistically significant difference exists for the fetal binocular distance between fetuses of Moroccan origin versus those of autochthonous Belgian or Turkish origin. This difference is of no clinical importance and there is no need to adapt reference charts for ethnicity when studying these three groups.

Adult↗

Fetal transverse cerebellar diameter in different ethnic groups.

AIMS: Transverse cerebellar diameter has been described as a tool to check for gestational age, but there are no available studies that attempt to determine differences in transverse cerebellar diameter between groups of different ethnic origin. The present study was undertaken to check for differences in ultrasound-measured transverse cerebellar diameter between pregnant women of autochthonous Belgian origin and migrant women from Morocco and Turkey. METHODS: A prospective cross-sectional study was performed. Patients were pregnant women presenting between 17 and 40 weeks of gestational age. Only uncomplicated singleton pregnancies with a known date of the last menstrual period confirmed by first trimester ultrasound were included. The father of the child had to be of the same ethnic origin as the mother. Polynomial regression was fitted for the three different ethnic groups. RESULTS: The transverse cerebellar diameter was obtained in 471 singleton fetuses, including 333 Belgian, 69 Moroccan and 69 Turkish. F-tests on the residual sums of squares of different fits demonstrated significant effects of ethnicity on the regression of the measurement versus gestational age (P < 0.00005). In a third order polynomial regression model the second order coefficient was significantly higher and the third order coefficient was significantly lower for the Moroccan group. CONCLUSION: The transverse cerebellar diameter is not independent of the ethnic origin of the patient. When using the transverse cerebellar diameter for the evaluation of fetal growth or for dating a pregnancy, care should be taken to rely on charts appropriate for the ethnic group, as demonstrated here for Moroccan fetuses.

Anthropometry↗

Nonviral transfection of distinct types of human dendritic cells: high-efficiency gene transfer by electroporation into hematopoietic progenitor- but not monocyte-derived dendritic cells.

Human dendritic cells (DC) are highly professional antigen presenting cells for the priming of naive cytotoxic T cells. Gene transfer in DC would be a useful strategy to load DC with relevant de novo synthesized antigens for immunotherapeutical purposes. As a first step towards a DC-based gene therapy, we examined the efficiency of nonviral transfection in different types of cultured human dendritic cells with a humanized red-shifted green fluorescent protein reporter gene. Plasmid DNA transfection by electroporation or lipofection was used to transfect CD34+ progenitor cell-derived DC (PC-DC) and Langerhans' cells (PC-LC), as well as monocyte-derived DC (Mo-DC). While lipofection was unsuccessful in all types of DC, we obtained high-efficiency gene transfer by electroporation in PC-LC (16%) and PC-DC (12%). In contrast, electroporation was strikingly less efficient in Mo-DC (< or = 2%). The potent allostimulatory capacity of DC was still retained in electroporated PC-DC and PC-LC. In conclusion, electroporation of antigen expressing plasmid DNA is an efficient tool for nonviral gene transfer in PC-DC and PC-LC, but not in Mo-DC and could be useful for the development of DC-based tumor immunotherapy.

Antigens, CD34↗

An unexpected triplet heterotopic pregnancy after replacement of two embryos.

We report a case of a triplet heterotopic pregnancy consisting of an intrauterine monozygous twin pregnancy and a tubal pregnancy after replacement of only two embryos in an in-vitro fertilization cycle with donor spermatozoa. This case demonstrates that sonographic demonstration of two intrauterine pregnancies after transfer of two embryos does not exclude the presence of an ectopic pregnancy. As both heterotopic pregnancy and spontaneous monozygotic twinning are more frequent after the use of assisted reproductive techniques, this combination, although extremely rare, must be kept in mind, especially in older patients with pre-existing tubal damage.

Adult↗

Cervical pregnancy: three case reports and a review of the literature.

Three cases of cervical pregnancy are described: the incidence, the diagnostic approach and different therapeutic managements used for this rare type of ectopic pregnancy are discussed. The last case shows that hysterectomy can be avoided by early diagnosis and by an adequate tamponing technique to control haemorrhage. For this purpose, a three-way Dufour catheter was successfully used to rinse the uterus with heated saline, allowing evacuation of intrauterine blood after curettage and to tampon the cervix.

Adult↗

Fetal fibronectin detection for prediction of preterm birth in low risk women.

OBJECTIVE: To evaluate the clinical value of cervical fetal fibronectin detection by a quantitative enzyme-linked immunosorbent assay (ELISA) (PTDcheck, Adeza Biomedical, Sunnyvale, California, USA) as a screening tool for the prediction of preterm contractions and preterm delivery in an unselected population of pregnant women globally considered to be at low risk for preterm delivery (n = 133). DESIGN: A prospective study in which cervical fetal fibronectin samples were collected at two-week intervals between 26 and 36 weeks of gestation. SETTING: A regional training hospital. SUBJECTS: One hundred and thirty-three singleton pregnancies presenting consecutively at an antenatal clinic. MAIN OUTCOME MEASURE: Occurrence of preterm contractions and preterm delivery (delivery at < 37 weeks of gestation). RESULTS: Twenty-four (18%) patients were considered positive for the presence of fetal fibronectin. Overall 15 patients (11%) developed preterm contractions and, despite therapeutic intervention, 10 patients (8%) were delivered preterm. As a predictor for preterm contractions, cervical fetal fibronectin detection had a sensitivity of 47%, a specificity of 86%, a positive predictive value of 29% and a negative predictive value of 93%. As a predictor for preterm delivery, cervical fetal fibronectin detection had a sensitivity of 60%, a specificity of 85% a positive predictive value of 25% and a negative predictive value of 96%. CONCLUSIONS: Cervical fetal fibronectin determinations at a two-week sampling frequency for prediction of preterm birth in a general obstetric population at low risk for preterm birth has limited clinical value as a routinely performed screening procedure.

Adult↗

Serum hCG decline following salpingotomy or salpingectomy for extrauterine pregnancy.

Twenty-five women with ectopic pregnancy were surgically treated, fifteen by conservative salpingotomy and ten by radical salpingectomy. All patients showed a clinically normal postoperative course. Serum human chorionic gonadotropin (hCG) levels were determined serially before and after the surgical procedure until non-pregnant values (< 5 mI.U./ml) were reached. Serum hCG decline was compared between patients treated by salpingotomy versus salpingectomy, using calculated hCG half-life times. We observed a significantly slower decline of serum hCG levels during the early phase of hCG disappearance in patients treated by salpingotomy versus patients treated by salpingectomy.

Chorionic Gonadotropin↗

Successful triplet pregnancy in a patient with a unicornuate uterus with a cavitary communicating rudimentary horn.

In a patient with primary infertility, ovulation was induced by monitored stimulation with human menopausal gonadotrophins (HMG) because of polycystic ovarian disease. Infertility work-up had shown a unicornuate uterus with a cavitary communicating rudimentary horn. The husband showed a varicocele-related moderate oligo-asthenoteratozoospermia. A triplet pregnancy occurred in a third HMG ovulation induction cycle combined with intra-uterine insemination of the husband's washed semen. The pregnancy was carefully monitored, and measures to prevent premature delivery were taken. Because of the patient's obvious discomfort in the presence of premature labour, Caesarean section was performed at 33 weeks gestation and three healthy infants were delivered. This is the first report of a successful triplet pregnancy in a women with a unicornuate uterus. The reproductive and obstetric outcome of this condition in general, and in the case of multiple pregnancy, is discussed.

Adult↗

Preliminary results with the use of the ROM-check immunoassay in the early detection of rupture of the amniotic membranes.

The unequivocal presence of amniotic fluid in the vagina is an important clinical sign of rupture of amniotic membranes, entailing impending delivery or risk for chorioamnionitis. Commonly used methods for detection of amniotic fluid in the vagina include pooling, ferning, nitrazine paper, ultrasound measurement of amniotic sac dimensions, dye injection or measurement of prolactin in vaginal secretions. These results are either difficult to interpret or are obtained after an invasive or expensive procedure. Measurement of alphafetoprotein (AFP) in vaginal secretions has also been considered for this application, but has proven unreliable due to its similar concentration in maternal plasma and amniotic fluid in the third trimester of pregnancy. We have evaluated a recently introduced method, the ROM-check Immunoassay (Adeza Biomedical, Sunnyvale, CA, USA) which is based on the detection of a fetal isoform of fibronectin in vaginal secretions when amniotic fluid is present. Our aim was to establish the reliability and clinical efficacy of this test in a number of obstetrical situations with unequivocal or equivocal rupture of the membranes (ROM). We conclude that in cases of unequivocal rupture and/or intactness of membranes, results of the ROM-check Immunoassay correspond well with the clinical findings, whereas in clinically equivocal rupture of the membranes, the test may add proof to the clinical suspicion of ROM but has to be interpreted with caution along with other clinical and non-clinical parameters.

Amniotic Fluid↗