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Biomedical subjects

M van Dijk

Publications and source records attributed to M van Dijk.

At least 37 records · Page 2Linked to original sources
PubMed2001

Mutation detection for exons 2 to 10 of the polycystic kidney disease 1 (PKD1)-gene by DGGE.

The PKD1-gene encodes a 14 kb transcript spanning a 50 kb genomic interval. Two-thirds of the gene is reiterated at another locus on the same chromosome. Using Long Range PCR with primers in intron 1 and exon 11, 6.8 kb PKD1 specific fragments were generated on genomic DNA. These products were used as templates for nested PCR's to screen exons 2-10 by Denaturing Gradient Gel Electrophoresis (DGGE). Upon analysis of 36 patients, a total of 11 different sequence variants were observed: A nonsense mutation in exon 2, a frameshift mutation in exon 8 and furthermore, two amino acid changes, two silent polymorphisms and five intronic variants.

Adult↗
PubMed2001

Analgesic efficacy of rectal versus oral acetaminophen in children after major craniofacial surgery.

BACKGROUND: Analgesic acetaminophen (INN, paracetamol) plasma concentrations after major surgery in neonates and infants have not yet been established in the literature. We therefore conducted a study in our intensive care unit. METHODS: Forty children, mean (standard deviation) age, 10.3 (2.3) months, received 20 mg/kg acetaminophen either orally (n = 20) or rectally (n = 20) every 6 hours after a rectal loading dose (40 mg/kg) during elective craniofacial correction. Blood samples were taken 1 hour before and 2 hours after administration of acetaminophen maintenance doses; pain scores were obtained every 3 hours. RESULTS: Acetaminophen plasma concentrations were higher in patients receiving rectal acetaminophen (mean area under the concentration-time curve [AUC], 171.2 mg x h/L) than in patients receiving oral acetaminophen (mean AUC, 111.9 mg x h/L). Pain scores were higher in patients receiving oral acetaminophen. However, after exclusion of the patients who vomited from the group receiving oral acetaminophen, acetaminophen plasma concentrations and pain scores did not differ between the groups. There was no relation between acetaminophen plasma concentrations and pain scores. Although 9 of all 40 patients (22.5%) did not reach the expected analgesic acetaminophen plasma concentrations of 10- to 20 mg/L, <7.5% of the visual analog scale pain scores exceeded 4 cm, which was considered as a cutoff point. CONCLUSION: These are the first data showing that the analgesic acetaminophen plasma concentration after major surgery in this age group does not always reach the 10 to 20 mg/L level. These data also show that, after a rectal loading dose of 40 mg/kg has been given during surgery, the best way of administering acetaminophen after craniofacial surgery is the rectal route.

Acetaminophen↗
PubMed2001

Hormonal and metabolic stress responses after major surgery in children aged 0-3 years: a double-blind, randomized trial comparing the effects of continuous versus intermittent morphine.

Children aged 0-3 yr were stratified for age and randomized to receive either continuous morphine (CM, 10 microg x kg(-1) x h(-1)) with three-hourly placebo boluses or intermittent morphine (IM, 30 microg x kg(-1) every 3 h) with a placebo infusion for postoperative analgesia. Plasma concentrations of epinephrine, norepinephrine, insulin, glucose and lactate were measured before and at the end of surgery and 6, 12 and 24 h after surgery. Pain was assessed with validated pain scales [the COMFORT scale and a visual analogue scale (VAS)] with the availability of additional morphine doses. Minor differences occurred between the randomized treatment groups, the oldest IM group (aged 1-3 yr) having a higher blood glucose concentration (P=0.003), mean arterial pressure (P=0.02) and COMFORT score (P=0.02) than the CM group. In the neonates, preoperative plasma concentrations of norepinephrine (P=0.01) and lactate (P<0.001) were significantly higher, while the postoperative plasma concentrations of epinephrine were significantly lower (P<0.001) and plasma concentrations of insulin significantly higher (P<0.005) than in the older age groups. Postoperative pain scores (P<0.003) and morphine consumption (P<0.001) were significantly lower in the neonates than in the older age groups. Our results show that continuous infusion of morphine does not provide any major advantages over intermittent morphine boluses for postoperative analgesia in neonates and infants.

Age Distribution↗
PubMed2000

Transcription-coupled and global genome repair differentially influence UV-B-induced acute skin effects and systemic immunosuppression.

Exposure to UV-B radiation impairs immune responses in mammals by inhibiting especially Th1-mediated contact hypersensitivity and delayed-type hypersensitivity. Immunomodulation is not restricted to the exposed skin, but is also observed at distant sites, indicating the existence of mediating factors such as products from exposed skin cells or photoactivated factors present in the superficial layers. DNA damage appears to play a key role, because enhanced nucleotide excision repair (NER) strongly counteracts immunosuppression. To determine the effects of the type and genomic location of UV-induced DNA damage on immunosuppression and acute skin reactions (edema and erythema) four congenic mouse strains carrying different defects in NER were compared: CSB and XPC mice lacking transcription-coupled or global genome NER, respectively, as well as XPA and TTD/XPD mice carrying complete or partial defects in both NER subpathways, respectively. The major conclusions are that 1) transcription-coupled DNA repair is the dominant determinant in protection against acute skin effects; 2) systemic immunomodulation is only affected when both NER subpathways are compromised; and 3) sunburn is not related to UV-B-induced immunosuppression.

Animals↗
PubMed2000

Thoracoscopically assisted total en bloc spondylectomy: two case reports.

We describe a combined surgical technique for tumors of the thoracic spine consisting of a thoracoscopically assisted ventral release followed by a dorsal en bloc spondylectomy and reconstruction. The technique enables thoracoscopic access and release of the involved spinal segment(s) to achieve surgical and histopathologic wide margins, avoiding the disadvantages inherent to thoracotomy. Two patients were successfully treated with solitary tumors involving T10 and T7-8 vertebra. The resection margins were free of tumor. Thoracoscopically assisted total en bloc spondylectomy allows wide excision of thoracic spinal tumors with free resection margins in selected patients; the operation can be performed under direct vision without contamination of uninvolved parts.

Adenocarcinoma, Follicular↗
PubMed2000

The reliability and validity of the COMFORT scale as a postoperative pain instrument in 0 to 3-year-old infants.

The aim of this study was to test the reliability and validity of the COMFORT scale as a postoperative pain instrument for children aged 0-3 years. Subjects were 158 neonates and toddlers after major abdominal or thoracic surgery. Trained nurses rated the children's pain at 3, 6 and 9 h postoperative on the Pediatric Surgical Intensive Care Unit using the COMFORT and a VAS for pain. Interrater reliability of the COMFORT items proved to be good (Kappa 0.63-0.93) for all items with the exception of the item 'Respiratory response', which was moderate (Kappa 0.54). LISREL analyses showed that the structure of the COMFORT data was best represented by three latent variables: COMFORT 'behaviour' with loadings from the behavioural items (Alertness, Calmness, Respiratory response/Crying, Physical movement, Muscle tone and Facial tension) and separate latent variables for 'Heart rate baseline' (HR) and 'Mean arterial blood pressure baseline' (MAP). Factor loadings of the items were invariant across time, indicating stability of the structure. The latent variables COMFORT 'behaviour' and VAS pain were highly interrelated indicating congruent validity. Stability of COMFORT 'behaviour' and VAS pain was moderate which might be due to varying painful episodes in this sample. HR and MAP, although stable across time, were weakly related to VAS pain and COMFORT 'behaviour'. These findings support the use of the COMFORT 'behaviour' scale to assess postoperative pain in neonates and infants.

Blood Pressure↗
PubMed2000

Interleukin-10 is an unequivocal Th2 parameter in the rat, whereas interleukin-4 is not.

Exposure of Wistar rats to the immunotoxic compounds hexachlorobenzene (HCB), bis(tri-n-butyltin)oxide, and benzo(a)pyrene was previously found to affect mRNA expression of interleukin (IL)-2, IL-2R alpha-chain, and interferon (IFN)-gamma, the prototypic Th1 cytokine. In contrast, the mRNA expression of IL-4, the prototypic Th2 cytokine, was unaffected. This latter finding suggested that the IL-4 mRNA expression may not be an unequivocal parameter for Th2 responses in the rat. In order to obtain such a parameter the present study was performed, consisting of two types of experiments. Expression and production of IL-4 as well as IL-10, a second Th2 cytokine, were measured. First, Lewis (Th1 prone) and Brown Norway (BN; Th2 prone) rats were exposed to HCB. Exposure was previously found to increase the serum immunoglobulin (Ig)E levels, an IL-4-dependent response, in BN but not Lewis rats, and in Lewis rats to aggravate experimental allergic encephalomyelitis (EAE), severity being inversely related to IL-10 levels. Secondly, BN rats were infected with Trichinella spiralis, an infection previously found to induce IL-4 production. HCB exposure did not affect IL-4 mRNA expression in either strain, while IL-4 production was decreased in Lewis and unaffected in BN rats. In Lewis rats both the mRNA expression and the production of IL-10 were decreased. The T. spiralis infection induced IL-4 and IL-10 mRNA expression, as well as IL-10 production. In contrast, the IL-4 production was strongly reduced. Thus, both the IL-10 mRNA expression and production correlated with the EAE development and T. spiralis infection. In HCB exposed Lewis rats and T. spiralis infected BN rats the IL-4 mRNA expression correlated with IgE levels and T. spiralis infection, respectively, whereas the IL-4 production lacked correlation in all cases. Collectively, these results suggest that IL-10 is an unequivocal Th2 parameter in the rat, whereas IL-4 is not.

Animals↗
PubMed2000

Total sacrectomy and reconstruction: oncologic and functional outcome.

The oncologic and functional outcomes of nine patients who were treated by total sacrectomy through L5 (three cases) or L5-S1 (six cases) were reviewed. Histologic diagnoses were one osteosarcoma, two giant cell tumors, two chondrosarcomas, and four chordomas. Patients' ages ranged from 17 to 70 years (mean age, 44.5 years). Resection margins were intralesional (giant cell tumors) in two, marginal in one, and wide in six patients (one contaminated). Reconstruction was performed using polymethylmethacrylate in two, screw and plate fixation in one, and a custom-made device in one. In five patients no reconstruction was performed. Five patients (45.5%) had wound complications: one had a wound dehiscence and two had deep infection; all needed surgical reintervention. In addition, in one a ventral and in another a dorsal hernia developed; only the ventral hernia was revised successfully. One patient had a deep vein thrombosis that was treated with a Coumadin derivate. Three patients (33%) died after 14, 18, and 50 months postoperatively respectively. One died of lung and widespread metastases, and two died of local recurrence and metastases. One patient with a giant cell tumor had a solitary lung metastasis. After resection the patient has been disease-free more than 90 months. At followup, six patients had no evidence of disease (mean followup, 73 months; range, 30-120 months). Functionally, there was no correlation between patients who had a reconstruction and those who had not. Total sacrectomy is a valuable procedure to secure local tumor control and overall survival, despite potential complications and neurologic and sexual dysfunction.

Adolescent↗
PubMed2000

Improved healing of extraperitoneal intestinal anastomoses in the early phase when surrounded by omentum.

BACKGROUND: The extra-anatomical position of a cervical oesophagogastrostomy is a reason for impaired anastomotic healing, but transposition of the omentum that is covered with mesothelial cells may be a way to improve that. METHOD: This hypothesis was tested in a rat model. An end-to-end jejuno-jejunostomy was placed subcutaneously in group I (n = 29), subcutaneously surrounded by omentum in group II (n = 29) and intra-abdominally surrounded by omentum in group III (n = 20). After 3, 7 or 14 days, the rats were sacrificed and bursting pressure (BP) of the anastomosis or jejunum was measured and the hydroxyproline (HP) level was determined. RESULTS: In group I 5/29, in group II 2/29 and in group III 0/20 rats died following anastomotic leakage (nonsignificant) and were excluded from other measurements. BP was decreased after 3 days in group I (60+/-9 mm Hg) compared with group II (101+/-8 mm Hg) and group III (107+/-11 mm Hg) (p = 0.002). After 7 days, BP in groups I (122+/-10 mm Hg) and II (132+/-10 mm Hg) were lower as compared with group III (230+/-8 mm Hg) (p<0.001). Differences in HP levels were not statistically significant between the groups after 3, 7 and 14 days. CONCLUSION: The healing of intestinal anastomoses in an extraperitoneal position is improved in the early phase only when surrounded by omentum.

Anastomosis, Surgical↗
PubMed1999

Towards prediction and modulation of treatment response.

The purpose of this paper is to evaluate new predictive assays and their potential to modulate treatment response. Their impact is presented in the context of three EORTC clinical trials in head and neck, lung and breast cancer, showing an improvement in survival by accelerated fractionation, concomitant use of cisplatin and radiotherapy and adjuvant hormonal treatment, respectively. Assays have been developed to predict the response to treatment by measuring tumor characteristics, such as the growth potential by the labeling index after i.v. injection of IdUrd, the extent of radiation-induced stable and unstable chromosome aberrations and the induction of apoptosis. These assays could guide us in the adaptation of the individual radiation doses and fractionation schedules. The measurement of the effect of cisplatin on DNA has become feasible with the development of antibodies against DNA adducts. In a recently completed phase II dose escalation trial with concomitant radiotherapy and daily cisplatin in lung cancer, we found that patients with high DNA adduct levels measured in the buccal mucosa, had a much better survival rate than patients with a low or undetectable amount of cisplatin DNA adducts. A better understanding of the signal transduction pathways involved in radiation-induced apoptosis may help to design studies aimed at modulating the apoptotic response. We and others have recently shown that alkylphospholipids, which inhibit mitogenic signaling, induce apoptosis in a variety of tumor cell lines. In combination with ionizing radiation, these compounds cause an enhancement of apoptotic cell kill. This type of signaling-based intervention study may form the basis for new therapeutic strategies. Pretreatment levels of apoptosis may be helpful in predicting treatment outcome, although the data so far show inconsistent results. The importance of evaluating other tumor-biological parameters, including cell kinetics should be stressed. Based on assays predicting reliably the response to hormonal therapy, a more appropriate choice can be made for therapeutic intervention with hormonal therapy and for selecting the appropriate adjuvant therapy in breast cancer patients. The development of a functional estrogen receptor assay (ER-FASAY), based on a yeast growth-assay, provides a way of estimating abnormal function of the receptor in tumors with a positive estrogen receptor score as measured by a classical immuno-histochemistry assay. This yeast assay can also detect different DNA mutations of the estrogen receptor existing in an individual tumor specimen.

Antineoplastic Agents↗
PubMed1999

Recurrent osteoblastoma of the hamate bone. A two-stage reconstruction with a free vascularized iliac crest flap.

An osteoblastoma in a carpal bone is very rare and presents a problem of reconstruction after wide tumour excision. We report a case of recurrent osteoblastoma of the right hamate bone with involvement of the ulnar carpal bones and soft tissues that was successfully treated by en bloc resection, temporary interposition of bone cement and fixation with K-wires, followed by reconstruction with a free vascularized iliac crest flap, tailored to the exact size of the defect, in a second procedure. Rapid fusion was achieved and hand function preserved with no evidence of recurrence 3 years postoperatively.

Adult↗
PubMed1997

A gain of novel tissue specificity in the human Ly-6 gene E48.

The Ly-6 Ag family consists of glycosyl-phosphatidylinositol-anchored surface proteins with a molecular mass of about 15 kDa. Seven members of the murine family have been characterized, and from five of these the genes have been cloned. Three members of the human family have been characterized: CD59, Ag E48, and the RIG-E or TSA-1/Sca-2 Ag. Most of the genes are expressed on lymphocytes, but some are expressed on other tissues as well. The mapped genes of the murine Ly-6 Ags, as well as of CD59, were shown to have a highly conserved structure, each consisting of four exons. The human E48 Ag was originally identified as a target Ag for radioimmunotherapy of patients with squamous cell carcinoma. The Ag is expressed on keratinocytes, but evidently not on lymphocytes. Molecular cloning of the cDNA encoding the Ag revealed that this Ag is most likely the human homologue of the murine Ly-6 Ag, ThB. In this paper, we describe that, in contrast to all other Ly-6 genes, the gene encoding the human E48 Ag consists of only three exons. Sequences at the 5' end of the transcription start site were shown to drive keratinocyte-associated expression. These data suggest that the functional elimination of an ancestral Ly-6 exon 1 switched the expression from lymphocytes toward keratinocytes.

Animals↗
PubMed1997

Diacylglycerol generated by exogenous phospholipase C activates the mitogen-activated protein kinase pathway independent of Ras- and phorbol ester-sensitive protein kinase C: dependence on protein kinase C-zeta.

The role of diacylglycerol (DG) formation from phosphatidylcholine in mitogenic signal transduction is poorly understood. We have generated this lipid at the plasma membrane by treating Rat-1 fibroblasts with bacterial phosphatidylcholine-specific phospholipase C (PC-PLC). This treatment leads to activation of mitogen-activated protein kinase (MAPK). However, unlike platelet-derived growth factor (PDGF) or epidermal growth factor (EGF), PC-PLC fails to activate Ras and to induce DNA synthesis, and activates MAPK only transiently (<45 min). Down-regulation of protein kinase C (PKC) -alpha, -delta and -epsilon isotypes has little or no effect on MAPK activation by either PC-PLC or growth factors. However, Ro 31-8220, a highly selective inhibitor of all PKC isotypes, including atypical PKC-zeta but not Raf-1, blocks MAPK activation by PDGF and PC-PLC, but not that by EGF, suggesting that atypical PKC mediates the PDGF and PC-PLC signal. In line with this, PKC-zeta is activated by PC-PLC and PDGF, but not by EGF, as shown by a kinase assay in vitro, using biotinylated epsilon-peptide as a substrate. Furthermore, dominant-negative PKC-zeta inhibits, while (wild-type) PKC-zeta overexpression enhances MAPK activation by PDGF and PC-PLC. The results suggest that DG generated by PC-PLC can activate the MAPK pathway independent of Ras and phorbol-ester-sensitive PKC but, instead, via PKC-zeta.

Animals↗
PubMed1996

Reproducibility of quantitative measurements from intracoronary ultrasound images. Beat-to-beat variability and influence of the cardiac cycle.

OBJECTIVES: The purpose of this study was to determine the variability of quantitative measurements from intracoronary ultrasound images, and the influence of the cardiac cycle on this variability, as a basis for in vivo applications. METHODS: Two observers analysed 30 MHz cross-sectional images from 96 in-vivo coronary arterial sites. By computer-assisted contour tracing we determined lumen area, vessel area, lesion area (vessel area minus lumen area) and percent obstruction (100% x lesion area/vessel area). Intra- and inter-observer and beat-to-beat variability, and systolic to diastolic differences were calculated by paired analysis. RESULTS: Consistent intra- and inter-observer differences (bias) were small (< or = 0.9%). Random variations in the two direct parameters were < or = 21.1%, but for the two derived parameters they were up to 40%. For all four parameters, random inter-observer variability was significantly greater (up to 119% for vessel area: 19.3 vs 8.8%) than intra-observer variability, but consistent variability was similar. Consistent beat-to-beat differences were small (< or = 1.4%), random variations were 8.9% to 17.5%. Random beat-to-beat variability for all four parameters was greater in diastolic than in systolic frames (up to 47.0% difference (11.9 vs 17.5%) for lesion area). Vascular dimensions were significantly greater in systole (2%). We found an error of 0.24 mm (2SD) for intra-observer variability of calculated mean arterial diameters, which is similar to the error described in angiographic studies (0.22 mm). CONCLUSIONS: Quantitative measurements from intracoronary ultrasound images generally reproduce well. It is preferable to use directly measured parameters as opposed to derived parameters, as they are less subject to variability. Variability can be reduced by selecting systolic images.

Adult↗
PubMed1995

The human E48 antigen, highly homologous to the murine Ly-6 antigen ThB, is a GPI-anchored molecule apparently involved in keratinocyte cell-cell adhesion.

The E48 antigen, a putative human homologue of the 20-kD protein present in desmosomal preparations of bovine muzzle, and formerly called desmoglein III (dg4), is a promising target antigen for antibody-based therapy of squamous cell carcinoma in man. To anticipate the effect of high antibody dose treatment, and to evaluate the possible biological involvement of the antigen in carcinogenesis, we set out to molecularly characterize the antigen. A cDNA clone encoding the E48 antigen was isolated by expression cloning in COS cells. Sequence analysis revealed that the clone contained an open reading frame of 128 amino acids, encoding a core protein of 13,286 kD. Database searching showed that the E48 antigen has a high level of sequence similarity with the mouse ThB antigen, a member of the Ly-6 antigen family. Phosphatidylinositol-specific (PI-specific) phospholipase-C treatment indicated that the E48 antigen is glycosylphosphatidylinositol-anchored (GPI-anchored) to the plasma membrane. The gene encoding the E48 antigen is a single copy gene, located on human chromosome 8 in the 8q24-qter region. The expression of the gene is confined to keratinocytes and squamous tumor cells. The putative mouse homologue, the ThB antigen, originally identified as an antigen on cells of the lymphocyte lineage, was shown to be highly expressed in squamous mouse epithelia. Moreover, the ThB expression level is in keratinocytes, in contrast to that in lymphocytes, not mouse strain related. Transfection of mouse SV40-polyoma transformed mouse NIH/3T3 cells with the E48 cDNA confirmed that the antigen is likely to be involved in cell-cell adhesion.

Amino Acid Sequence↗
PubMed1995

Specific immunologic recognition of the tumor-specific E2A-PBX1 fusion-point antigen in t(1;19)-positive pre-B cells.

The t(1;19) translocation is the most commonly observed chromosomal translocation in childhood acute lymphoblastic leukemia (ALL). Its presence among pre-B cell ALL cases, has been associated with a poor prognosis. Two genes, E2A and PBX1, are involved in this t(1;19) translocation. As a consequence, parts of the E2A and PBX1 genes are fused, resulting in a chimeric E2A-PBX1 gene, encoding chimeric E2A-PBX1 proteins. As such, the amino acid sequence at the fusion site represents a unique tumor-specific determinant. We report on the generation of a polyclonal antiserum, termed BP 1/19, raised against the tumor-specific E2A-PBX1 junction of E2A-PBX1 proteins. The specificity of antiserum BP 1/19 for the E2A-PBX1 fusion-point is demonstrated at the peptide and at the protein level. Furthermore, specific binding of antiserum BP 1/19 to t(1;19) positive cells was shown using immunofluorescence techniques. The study shows that: (1) the tumor-specific fusion-point epitope on E2A-PBX1 proteins is presented in an antigenic fashion, and (2) this particular fusion-point epitope can be used in immunological marker analysis using fluorescence microscopy.

Amino Acid Sequence↗