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Biomedical subjects

L Vermeulen

Publications and source records attributed to L Vermeulen.

At least 19 recordsLinked to original sources
PubMed2001

Assessing the quality of life in children with cystic fibrosis.

Although patients with cystic fibrosis (CF) are experiencing increased longevity, it is unclear that improved quality of life (QoL) accompanies the greater quantity of life. This is especially true of children with CF where the burdens of treatment are substantial. Assessing QoL in such children is difficult, and only one instrument--the Quality of Well-Being (QWB) scale--seems to have been used extensively to assess QoL in children with CF. After thoroughly reviewing the literature, we surveyed the 113 certified CF centers in the United States about QoL assessment. With 84% responding, it was found that only 7 centers are assessing QoL--4 have been using the QWB instrument. Concurrently, we pilot tested the QWB instrument in children being followed longitudinally in the Wisconsin CF Neonatal Screening Project. Our results indicated that QWB scores reflecting QoL decreased as the number of respiratory infections increased, as the number of concurrent medical conditions increased, and as the number of different medications increased. However, we recognized problems with the assessed domains and data interpretation. In fact, the QWB instrument has limited sensitivity and responds more to the extent of physician-determined treatment than to QoL. There is a need for more QoL assessment and better instruments, particularly in young children with CF.

Child↗
PubMed2000

Signal transduction by tumor necrosis factor and gene regulation of the inflammatory cytokine interleukin-6.

Interleukin (IL)-6 is a multifunctional cytokine that can be induced by a plethora of chemical or physiological compounds, including the inflammatory cytokines tumor necrosis factor (TNF) and IL-1. The molecule TNF has a trimeric configuration and thus binds to membrane-bound, cellular receptors to initiate cell death mechanisms and signaling pathways leading to gene induction. Previously, we showed that induced clustering of the intracellular domains of the p55 TNF receptor, or of their respective 'death domains' only, is sufficient to activate the nuclear factor kappa B (NF-kappa B) and several mitogen-activated protein kinase (MAPK) pathways. NF-kappa B is the exclusive transcription factor for induction of the IL-6 gene in response to TNF and functions as the final trigger to activate a multiprotein complex, a so-called 'enhanceosome', at the level of the IL-6 promoter. Furthermore, the enhanceosome displays histone acetylation activity, which turned out to be essential for IL-6 gene activation via NF-kappa B. However, activation of NF-kappa B alone is not sufficient for IL-6 gene induction in response to TNF, as inhibition of the coactivated extracellular signal-regulated kinase and p38 MAPK pathways blocks TNF-mediated gene expression. Nevertheless, the transactivating NF-kappa B subunit p65 is not a direct target of MAPK phosphorylation. Thus, we postulated that other components of the enhanceosome complex are sensitive to MAPK cascades and found that MAPK activity is unequivocally linked to the histone acetylation capacity of the enhanceosome to stimulate gene expression in response to TNF. In contrast, glucocorticoid repression of TNF-driven IL-6 gene expression does not depend on abrogation of histone acetyltransferase activity, but originates from interference of the liganded glucocorticoid receptor with the contacts between NF-kappa B p65 and the promoter configuration around the TATA box.

Animals↗
PubMed2000

Activity and dosage of alteplase dilution for clearing occlusions of venous-access devices.

The activity and sterility of reconstituted alteplase solution and the effectiveness of an alteplase dose-escalation protocol for the clearance of midline-catheter and central-venous-access device occlusions were studied. Reconstituted alteplase solution was stored at -70, -25, or 2 degrees C at concentrations of 0.5, 1, or 2 mg/mL. Durations of storage in the freezer were 0, 7, and 14 days, and durations of storage in the refrigerator were 0, 48, and 72 hours and 7 and 14 days. Samples were also assayed and cultured without prior freezing after refrigeration at 2 degrees C for 0, 48, and 72 hours and 7, 14, and 28 days. Fifty-eight pediatric and adult patients were enrolled in a separate study in which catheter clearance was initiated with alteplase 0.5 mg, and the dose was escalated to 1 and 2 mg sequentially until the catheter was cleared. The primary endpoint was restoration of catheter patency, and the secondary endpoint was the occurrence of bleeding episodes within 24 hours of alteplase administration. Catheter removal due to failure to restore patency was also documented. The activity and sterility of alteplase were maintained under all conditions studied. Fifty catheters (86.2%) were cleared with alteplase 0.5 mg, 5 (8.6%) after dose escalation to 1 mg, and 1 (1.7%) after escalation to 2 mg. The alteplase solution did not clear the occlusion in 2 catheters (3.4%): 1 had a mechanical obstruction and 1 cleared two hours after the 1-mg dose was deemed a failure. None of the six catheter removals was due to recalcitrant clots. Bleeding observed was not considered to be the result of alteplase administration. For use in clearing occlusions of venous-access devices, alteplase 0.5, 1, and 2 mg/mL retained sufficient fibrinolytic activity when stored for up to 14 days at 2 degrees C (28 days for the 0.5-mg/mL dilution) and when stored for 14 days at -70 or -25 degrees C followed by up to 14 days at 2 degrees C. The dose-escalation protocol was effective.

Adolescent↗
PubMed2000

Glucocorticoids repress NF-kappaB-driven genes by disturbing the interaction of p65 with the basal transcription machinery, irrespective of coactivator levels in the cell.

Glucocorticoids (GCs) are used to combat inflammatory diseases. Their beneficial effect relies mainly on the inhibition of NF-kappaB- and/or AP-1-driven proinflammatory gene expression. Previously, we have shown that GCs repress tumor necrosis factor-induced IL-6 gene expression by an NF-kappaB-dependent nuclear mechanism without changing the DNA-binding capacity of NF-kappaB or the expression levels of the cytoplasmic inhibitor of NF-kappaB (IkappaB-alpha). In the present work, we investigate the effect of GC repression on different natural and/or recombinant NF-kappaB-driven reporter gene constructs in the presence of increasing amounts of various coactivator molecules, such as CREB-binding protein (CBP), p300, and SRC-1. We found that GCs maintain their repressive capacities, irrespective of the amount of cofactor present in the cell. Similar results were obtained for the reciprocal transrepression of a GC receptor (GR) element-driven reporter gene by p65. We demonstrate that neither the expression levels of p65 and CBP nor their physical association are affected by activated GR. Using Gal4 chimeras, we show that repression by GCs is specific for p65-mediated transactivation, ruling out competition for limiting nuclear factors as the major underlying mechanism of gene repression. In addition, the transactivation potential of a point-mutated Gal4-p65 variant with a decreased CBP interaction capability is still repressed by GR. Finally, we present evidence that the specificity of GC repression on p65-driven gene expression is codetermined by the TATA box context.

Base Sequence↗
PubMed2000

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↗
PubMed1999

Enzymatic properties of rat group IIA and V phospholipases A(2) compared.

Group IIA and V phospholipases A(2) (PLA(2)s) are known to play a role in inflammatory responses. We have constructed a bacterial expression vector for rat group IIA and V PLA(2)s, over-expressed, folded and purified the proteins with the aim to study and compare the properties of the enzymes in detail. For zwitterionic phospholipid micelles, both enzymes display optimum activity at pH 8. 0 and absolutely require Ca(2+) for enzymatic activity. In the presence of substrate, group V PLA(2) has a high affinity for Ca(2+) (K(Ca2+)=90 microM) while K(Ca2+) of group IIA PLA(2) was found to be 1.6 mM. The absence of substrate only marginally influences the Ca(2+) affinities. In contrast to group IIA PLA(2), group V PLA(2) does not show a jump in the activity profile at substrate concentrations around the critical micelle concentration. Direct binding studies using n-alkylphosphocholines indicate that group V PLA(2) forms protein-lipid aggregates at pre-micellar lipid concentrations in a cooperative and Ca(2+)-dependent manner. This behavior, which is comparable to that observed for the PLA(2) from Naja melanoleuca snake venom, reflects the high affinity of this enzyme for zwitterionic phospholipids. Competitive inhibition by the substrate analogues (R)-2-dodecanoylaminohexanol-1-phosphocholine and its phosphoglycol derivative was tested on zwitterionic micelles as substrate. Group IIA PLA(2) shows a preference for the phosphoglycol inhibitor whereas the phosphocholine inhibitor binds stronger to the active site of group V PLA(2). The enzymatic activity was also measured on zwitterionic liposomes which appear to be much better substrates for group V PLA(2) than for group IIA PLA(2). The overall results suggest that group V PLA(2) is better suited for action on biological membranes than group IIA PLA(2).

Amino Acid Sequence↗
PubMed1996

Deterioration of sperm quality in young healthy Belgian men.

We have retrospectively analysed the sperm characteristics of 416 consecutive healthy young men who presented themselves in the past 19 years as candidate sperm donors. Ejaculate volume increased slightly (P = 0.067), and average sperm concentration decreased (P = 0.035) by 12.4 x 10(6)/ml over the observation period, so that sperm count per ejaculate remained unchanged (P = 0.91). In contrast, sperm morphology (r = - 0.23, P < 0.0001), rapid progressive motility (r = - 0.42, P < 0.0001) and total motility (r = - 0.33, P < 0.0001) presented an important and time-related decrease. When a quadratic model was used rather than a linear one to analyse the data on rapid progressive motility, there appeared to have been no further decline since 1990. The average proportion of spermatozoa with normal morphology decreased from 39.2% in the period 1977-1980 to 26.6% in 1990-1995 (P < 0.0001), and the mean percentage of spermatozoa with rapid progressive motility decreased from 52.7 to 31.7% (P < 0.0001). The percentage of candidate donors with sperm characteristics below the 5th percentile cut-off value of a normal fertile population increased from 13 to 54% during the observation period (P < 0.0001). Since the technique of semen analysis has remained essentially unchanged in-so-far as has been practically possible, as has the method of recruitment of candidate sperm donors, the observed deterioration of sperm characteristics is considered to reflect degeneration of sperm production among men aged between 20 and 40 years.

Adult↗
PubMed1995

Comparison of different methods for the investigation of antisperm antibodies on spermatozoa, in seminal plasma and in serum.

Since there is no gold standard for the diagnosis of immunological infertility, comparison between different methods and of their results with biological tests for the detection of antisperm antibodies must be used in defining the most reliable and clinically relevant method. We have evaluated the results of direct (n = 100) and indirect tests in serum (n = 140) and seminal plasma (n = 100) using the SpermMAR and Immunobead (IB) techniques for the detection of sperm antibodies of the immunoglobulin (Ig) classes G, A and M, and we have compared the results with those of the tray agglutination test and the adenosine triphosphate release cytotoxicity test. Results indicate the higher specificity and sensitivity of the SpermMAR results for IgG and IgA, as compared to the outcome of the IB test. It appears that the IB test for IgA may detect non-specific antibodies in serum. Little information is obtained from the tray agglutination test in seminal plasma, and the indirect SpermMar test for IgG in seminal plasma was the only independent variable associated with the outcome of the former test. Since the SpermMAR tests for IgG and IgA are more accurate and biologically relevant, as well as easier to perform than the respective IB tests, the former must be considered the method of first choice.

Agglutination Tests↗
PubMed1995

Human semen analysis.

Rapid developments have occurred in the management of couple infertility due to a male factor. These have stimulated renewed interest in semen analysis, which has become more correct, more reliable and more informative. The so-called basic semen analysis, which includes subjective estimation of sperm concentration, motility and morphology, has largely become obsolete. It has been replaced by several alternative techniques such as the home testing of semen by the man himself, the elaboration of methods and equipments for the exact assessment of conventional sperm characteristics, and the measurement of new parameters evaluating the functional state and capacity of spermatozoa, accessory sex glands and seminiferous epithelium. The present paper covers the following items: (i) conventional methods of semen analysis, (ii) the resazurin test and home fertility scoring, (iii) advanced methods for the objective assessment of conventional sperm characteristics and motility parameters.

Coloring Agents↗
PubMed1995

Androgens in seminal plasma: markers of the surface epithelium of the male reproductive tract.

Androgens in seminal plasma have been investigated in relation to other markers of the male reproductive system. Testosterone and dihydrotestosterone (DHT) were measured by radioimmunoassay after paper chromatography in 104 semen samples. Concentrations of testosterone and DHT were significantly lower in samples from patients with abnormal sperm characteristics than in men with normozoospermia. Both testosterone and DHT were correlated significantly with sperm concentration (r = 0.40, p < 0.001; r = 0.41, p < 0.001, respectively), motile sperm concentration (r = 0.35, p < 0.01; r = 0.35, p < 0.01) and ATP concentration (r = 0.59, p < 0.001; r = 0.45, p < 0.001). In addition, the total amounts of testosterone and DHT were correlated with total activity of alpha-glucosidase (r = 0.49, p < 0.001; r = 0.58, p < 0.01), and gamma-glutamyltransferase (r = 0.49, p < 0.001; r = 0.48, p < 0.001) in seminal plasma. Transferrin (Tf) concentration in seminal plasma was significantly lower in samples without spermatozoa, and total Tf content was lower in oligozoospermic samples (p < 0.05). Testosterone and DHT were correlated positively with Tf levels in seminal plasma (r = 0.48, p < 0.0001; r = 0.78, p < 0.0001 respectively). Testosterone, DHT and Tf in seminal plasma were higher in the first than in the second fraction of split ejaculates, and DHT, but not testosterone, increased significantly in each of six patients treated with tamoxifen. Testosterone, DHT, and Tf in seminal plasma were not correlated with serum concentrations of LH, FSH, testosterone or prolactin, but the DHT : T ratio in seminal plasma was correlated with serum LH (r = 0.36, p < 0.05). It is concluded that the concentration of androgens in seminal plasma is related predominantly to the activity of the seminiferous epithelium and, to a lesser extent, to the function of the accessory sex glands.

Adenosine Triphosphate↗
PubMed1995

Statement on the general reduction in sperm quality.

Over a period of 17 years, 360 young healthy men presented themselves as candidate donors for the sperm bank of the University Hospital of Ghent. Semen characteristics of these men were assessed using unaltered methods, and analysis was performed on the first sample delivered before any donor selection was performed. Sperm motility and morphology, but not the total sperm count per ejaculate, exhibited a highly significant decrease. Over 40% of candidate donors since 1990 exhibited subnormal sperm characteristics, as against only 5% of the group investigated before 1980.

Adult↗
PubMed1994

Methodological aspects of sperm morphology evaluation: comparison between strict and liberal criteria.

OBJECTIVE: To compare the methodological accuracy of different sperm morphology criteria. SETTING: A multicenter study including 10 laboratories with high expertise in semen analysis. PATIENTS: Semen preparations of subfertile men with a variable degree of teratozoospermia and of fertile semen donors. INTERVENTIONS: Detailed assessment of sperm morphology on 10 air-dried semen smears, of which 3 originated from the same ejaculate. RESULTS: The average coefficient of variation calculated on the three smears of the same ejaculate was higher when strict criteria for morphological normality were used and borderline cells were classified as abnormal than when criteria of abnormality were applied and borderline cells were considered normal. The correspondence between individual centers mutually and of each center with the average result of all centers was better when the latter approach was taken. The performance of two computer-assisted systems was intermediate between that of the two approaches, whereas one system gave unreliable results. CONCLUSIONS: Strict criteria for normality of sperm morphology, with borderline cells considered abnormal, gives results that are less reproducible and less accurate than the approach that classifies sperm as abnormal, with borderline cells considered normal.

Fertility↗
PubMed1994

Comparison of the resazurin test, adenosine triphosphate in semen, and various sperm parameters.

The results of the resazurin test (RES) and adenosine triphosphate (ATP) concentration in semen, measured by two methods, were compared for their ability to predict sperm parameters of semen samples from 42 subfertile men as assessed by a semi-computerized system. The highest correlation of RES grade was with sperm concentration (r = 0.70, P < 0.001), concentration of motile spermatozoa, concentration of motile spermatozoa with normal morphology and the ATP concentration using the reference LKB method (all r = 0.65, P < 0.001). The RES test has a positive predictive value of 93% for a progressive motile sperm concentration of 20 x 10(6)/ml or more, and a negative predictive power of 90% for the same variable at a criterion value of 10 x 10(6)/ml. The results of ATP measurement using the reference LKB and FireZyme methods presented a strong correlation (r = 0.74, P < 0.001). The correlations between ATP measurements from the FireZyme method and sperm characteristics were better than those obtained using the reference LKB method for ATP determination. It is concluded that the RES test can be performed with a relatively small volume of semen; it is easy to perform and requires not technical equipment. The accuracy and predictive value of this test are similar to more sophisticated ATP measurements. In addition, the RES may identify a subgroup of subfertile men with a decreased reducing capacity of semen.

Adenosine Triphosphate↗
PubMed1992

Objective semen analysis: has the target been reached?

Objectivity in assessing critical sperm characteristics such as concentration, motility and morphology, has been the target of many systems and devices. Methods based on physical principles such as turbidimetry, spectrophotometry, laser Doppler technology, are too imprecise or technically too complicated to be applied routinely in the laboratory. Microscopic images providing photographical, cinematographical or video data acquisition followed by manual or computer-assisted image analysis (CASA) suffer from practical and/or device deficiencies, making them tedious and time-consuming, or unreliable because of confounding factors and uncontrolled artefacts. A single-step computer system using visual evaluation of the microscopic field and manual tracking of sperm movement yields more reliable results, but technician expertise remains essential for correct performance. The scientific basis of multiple errors in semen aspiration, chamber quality, data acquisition and analysis is given. Biased interpretations of results or incorrect handling of statistical data are criticised.

Humans↗
PubMed1990

Possibilities and limitations of techniques of assisted reproduction for the treatment of male infertility.

Since relatively few spermatozoa are needed for oocyte fertilization during gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization (IVF), these methods have been applied in couples with infertility due to male causes. Forty-six couples with male factor infertility were enrolled in this study and results were compared with those attained in 48 couples treated with the same techniques for other than male causes. Overall, GIFT resulted in 26% ongoing pregnancies. GIFT seems to be particularly successful when the sperm concentration is 20 x 10(6)/ml or more, but sperm motility and/or morphology are poor. Nine pregnancies occurred out of 26 GIFT cycles in 18 cases selected on this basis. The ongoing pregnancy rate after IVF was 16% per patient. The latter treatment should be attempted in male immune infertility and in cases with a low sperm concentration, with or without abnormal sperm motility and/or morphology. In these circumstances, five pregnancies were attained out of 28 cycles in 14 cases. For similar sperm concentrations, the conception rate per cycle attained with techniques of assisted reproduction was more than twice that attained with conventional treatment of male infertility.

Female↗
PubMed1990

Value of sperm characteristics and the result of in-vitro fertilization for predicting the outcome of assisted reproduction.

The outcome of procedures for assisted reproduction, namely in-vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) were used as end-points to assess the capacity of particular sperm characteristics to predict the fertilizing potential of semen. In addition, the result of IVF performed with spare oocytes from the GIFT procedure, was used to predict the pregnancy outcome of GIFT. The power of sperm characteristics to predict the outcome of assisted reproduction procedures was poor. With regard to the outcome of IVF, sperm morphology was the best discriminant. The threshold value of 16% normal sperm morphology could be used as a good predictor of successful IVF, but could not be applied as a criterion to reject an IVF trial. For the latter purpose, the limit of 5% sperm with normal morphology should be used. The proportion of sperm with grade A motility in native semen provided the best discrimination between GIFT-fertile and GIFT-infertile cases. A negative result from IVF performed with spare oocytes was 93% accurate in predicting unsuccessful outcome of GIFT. Hence, diagnostic IVF is the most sensitive assay for male fertility. The occurrence of oocyte fertilization during IVF predicts a successful outcome of GIFT in only 50% of cases. Hence, a negative result in IVF indicates that semen is almost certainly infertile, but a positive result does not guarantee the successful outcome of GIFT.

Adult↗
PubMed1989

Determination of adenosine triphosphate in human semen to estimate the fertilizing potential and to quantify sperm antibodies.

The measurement of the ATP content of fresh semen is as accurate as the estimation of sperm motility by conventional methods in discriminating between semen of fertile versus subfertile men. The ATP content of frozen thawed donor semen is correlated with the probability of conception per cycle of insemination. Exact quantification of cytotoxic sperm antibodies in serum is possible with the adenosine-triphosphate-release-cytotoxicity test, since measurement is free of the bias of microscopic examination. The procedure has been simplified by testing only one serum dilution and calculating the 'sperm toxicity index'.

Adenosine Triphosphate↗