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Biomedical subjects

M van Dijk

Publications and source records attributed to M van Dijk.

At least 19 recordsLinked to original sources
PubMed2006

Effects of low-dose naloxone on opioid therapy in pediatric patients: a retrospective case-control study.

OBJECTIVE: To develop novel therapies that prevent opioid tolerance in critically ill children we examined the effects of low-dose naloxone infusions on patients' needs for analgesia or sedation. DESIGN AND SETTING: Matched case-control study in a pediatric intensive care unit at a university children's hospital. PATIENTS: We compared 14 pediatric ICU patients receiving low-dose naloxone and opioid infusions with 12 matched controls receiving opioid infusions. MEASUREMENTS AND MAIN RESULTS: Opioid analgesia and sedative requirements were assessed as morphine- and midazolam-equivalent doses, respectively. No differences were observed between groups in opioid doses at baseline or during naloxone, but in the postnaloxone period opioid doses tended to be lower in the naloxone group. Compared to baseline the naloxone group required more opioids during naloxone but fewer opioids after naloxone. Total sedative doses were comparable at baseline in both groups, with no differences in the postnaloxone period. The naloxone group required less sedation after naloxone but sedation doses were unchanged in controls. The two groups did not differ in pain scores, sedation scores, or opioid side effects. CONCLUSIONS: Naloxone did not reduce the need for opioid during the infusion period but tended to reduce opioid requirements in the postnaloxone period without additional need for sedation. Randomized clinical trials may examine the effects of low-dose naloxone on opioid tolerance and side effects in pediatric ICU patients requiring prolonged opioid analgesia.

Analgesia↗
PubMed2006

Pain assessment in profound cognitive impaired children using the Checklist Pain Behavior; is item reduction valid?

There are both commonalities and idiosyncratic features in the reaction of pain children with profound cognitive impairment (CI), and that there is no evidence to suggest that idiosyncratic behavior is more characteristic of this population than of any other population. The main objective of this study was to identify whether the 23-item version of the Checklist Pain Behavior could be reduced to 10 items. Previous research demonstrated that only these 10 items discriminated between absence and presence of pain. Second, we wanted to explore the underlying structure of these 10 selected items including its performance. Data of 477 observations in 73 children were used. All these children were video-taped while they were admitted to the Sophia Children's Hospital for surgery, twice before and five times after surgery. These video-tapes were scored by an independent observer. A visual analogue scale (VAS) by a researcher was used to assess the presence of pain. We tested whether the underlying structure was unidimensional, and whether it had differential qualities between pain and no pain, and to which degree. Using a modern psychometric method, i.e., Mokken scaling model, we unraveled the interdependency of the pain response in CI-children, in that the structure turned out to be unidimensional. In addition, these behaviors could be hierarchically ordered in terms of frequency of occurrences. Finally, these behaviors had to a high degree the potentialities to estimate the likelihood of occurrence of pain.

Adolescent↗
PubMed2006

Application of polylactides in spinal cages: studies in a goat model.

Spinal cages are currently made of non-resorbable materials, but they only have a temporary function: after fusion, resorption is desirable both from a biological and mechanical point of view. We studied different polylactides in stand-alone condition in a goat model. Cages were made of 100% poly(L-lactic acid) (PLLA) or 70/30 poly(L/DL-Lactic acid) (PLDLLA); titanium served as control. After six months, all titanium cages showed non-unions comparable to that observed in a clinical retrieval, thus showing validity of the goat model. PLLA cages maintained their mechanical integrity for six months, enough to allow fusion. After that, the material resorbed within 48 months without adverse tissue reactions. Bone formation was faster in PLDLLA cages, but these already failed within three months, thus losing their stabilising function: 50% ended in pseudo-arthrosis. Additional internal fixation provided enough stability for fusion (83%). Biocompatibility of both PLLA and PLDLLA was excellent. The long-term results show that PLLA cages can be used for stand-alone interbody fusion, and that PLLA is an improvement over titanium in terms of fusion rate. PLDLLA showed enhanced bone formation, but also earlier failure of the implant. Chances for spinal fusion were better with additional internal fixation.

Absorbable Implants↗
PubMed2005

Morphine in ventilated neonates: its effects on arterial blood pressure.

OBJECTIVE: To study the effects of continuous morphine infusion on arterial blood pressure in ventilated neonates. DESIGN: Blinded randomised placebo controlled trial. SETTING: Level III neonatal intensive care unit in two centres. PATIENTS: A total of 144 ventilated neonates. Inclusion criteria were postnatal age <3 days, ventilation <8 hours, and indwelling arterial line. Exclusion criteria were severe asphyxia, severe intraventricular haemorrhage, major congenital anomalies, neuromuscular blockers. INTERVENTION: Arterial blood pressure was measured before the start and during the first 48 hours of masked infusion of drug (morphine/placebo; 100 microg/kg + 10 microg/kg/h). OUTCOME MEASURES: Arterial blood pressure and blood pressure variability. RESULTS: There were no significant differences in overall mean arterial blood pressure between the morphine group (median (interquartile range) 36 mm Hg (6) and the placebo group (38 mm Hg (6)) (p = 0.11). Although significantly more morphine treated patients (70%) showed hypotension than the placebo group (47%) (p = 0.004), the use of volume expanders and vasopressor drugs was not significantly different (morphine group, 44%; placebo group, 48%; p = 0.87), indicating the limited clinical significance of this side effect. Blood pressure variability was not influenced by routine morphine analgesia (p = 0.81) or additional morphine (p = 0.80). Patients with and without intraventricular haemorrhage showed no differences in blood pressure (Mann-Whitney U test 1953; p = 0.14) or incidence of hypotension (chi(2) test 1.16; df 1; p = 0.28). CONCLUSIONS: Overall arterial blood pressure, use of inotropes, and blood pressure variability were not influenced by morphine infusion. Therefore the clinical impact of hypotension as a side effect of low dose morphine treatment in neonates is negligible.

Analgesics, Opioid↗
PubMed2005

Propofol 6% as sedative in children under 2 years of age following major craniofacial surgery.

BACKGROUND: After alarming reports concerning deaths after sedation with propofol, infusion of this drug was contraindicated by the US Food and Drug Administration in children <18 yr receiving intensive care. We describe our experiences with propofol 6%, a new formula, during postoperative sedation in non-ventilated children following craniofacial surgery. METHODS: In a prospective cohort study, children admitted to the paediatric surgical intensive care unit following major craniofacial surgery were randomly allocated to sedation with propofol 6% or midazolam, if judged necessary on the basis of a COMFORT behaviour score. Exclusion criteria were respiratory infection, allergy for proteins, propofol or midazolam, hypertriglyceridaemia, familial hypercholesterolaemia or epilepsy. We assessed the safety of propofol 6% with triglycerides (TG) and creatine phosphokinase (CPK) levels, blood gases and physiological parameters. Efficacy was assessed using the COMFORT behaviour scale, Visual Analogue Scale and Bispectral Index monitor. RESULTS: Twenty-two children were treated with propofol 6%, 23 were treated with midazolam and 10 other children did not need sedation. The median age was 10 (IQR 3-17) months in all groups. Median duration of infusion was 11 (range 6-18) h for propofol 6% and 14 (range 5-17) h for midazolam. TG levels remained normal and no metabolic acidosis or adverse events were observed during propofol or midazolam infusion. Four patients had increased CPK levels. CONCLUSION: We did not encounter any problems using propofol 6% as a sedative in children with a median age of 10 (IQR 3-17) months, with dosages <4 mg kg(-1) h(-1) during a median period of 11 (range 6-18) h.

Chemistry, Pharmaceutical↗
PubMed2005

Randomised controlled trial evaluating effects of morphine on plasma adrenaline/noradrenaline concentrations in newborns.

OBJECTIVES: To determine the effects of continuous morphine infusion in ventilated newborns on plasma concentrations of adrenaline (epinephrine) and noradrenaline (norepinephrine) and their relation to clinical outcome. DESIGN: Blinded, randomised, placebo controlled trial. SETTING: Level III neonatal intensive care units in two centres. PATIENTS: A total of 126 ventilated neonates (inclusion criteria: postnatal age <3 days, duration of ventilation <8 hours, indwelling arterial catheter for clinical purposes; exclusion criteria: severe asphyxia, severe intraventricular haemorrhage, major congenital anomalies, neuromuscular blockers). INTERVENTIONS: Plasma adrenaline and noradrenaline concentrations were determined in patients during blinded morphine (n = 60) and placebo (n = 66) infusion (100 microg/kg plus 10 microg/kg/h). RESULTS: Plasma concentrations at baseline (nmol/l with interquartile range in parentheses) were comparable in infants treated with morphine (adrenaline, 0.22 (0.31); noradrenaline, 2.52 (2.99)) or placebo (adrenaline, 0.29 (0.46); noradrenaline, 2.44 (3.14)). During infusion, median adrenaline concentrations were 0.12 (0.28) and 0.18 (0.35) and median noradrenaline concentrations were 2.8 (3.7) and 3.8 (4.0) for the morphine and placebo treated infants respectively. Multivariate analyses showed that noradrenaline (p = 0.029), but not adrenaline (p = 0.18), concentrations were significantly lower in the morphine group than the placebo group. Furthermore, noradrenaline concentrations were related to the length of stay in the neonatal intensive care unit. CONCLUSIONS: Continuous morphine infusion significantly decreased plasma noradrenaline concentrations in ventilated newborns compared with placebo treatment. The results of this study support the idea that routine morphine administration decreases stress responses in ventilated neonates.

Analgesics, Opioid↗
PubMed2004

Obliterative endophlebitis in mute swans (Cygnus olor) caused by Trichobilharzia sp. (Digenea: Schistosomatidae) infection.

Schistosome infections in mammals cause chronic proliferative vascular lesions associated with the presence of adult parasites in the lumen of mesenteric and portal veins. In birds, however, this has never been reported. In this study, we found obliterative endophlebitis associated with the presence of adult schistosomes (Trichobilharzia sp., probably Trichobilharzia filiformis) as the main pathologic finding in five of eight mute swans (Cygnus olor). On histologic examination, the intestinal and portal veins of these swans showed moderate to severe, diffuse, hyperplastic endophlebitis, characterized by myointimal hyperplasia, often with obliteration of the vascular lumen. In addition, moderate to severe lymphocytic and granulocytic enteritis occurred in all eight swans associated with the presence of schistosome eggs in the intestinal mucosa. Other findings included hepatic and splenic hemosiderosis and high hepatic copper levels. The vascular lesions associated with Trichobilharzia sp. infection may have contributed to the emaciation and death of those mute swans by obstruction of venous return in the intestinal and portal veins.

Animals↗
PubMed2003

Detection of a functional hybrid receptor gammac/GM-CSFRbeta in human hematopoietic CD34+ cells.

A functional hybrid receptor associating the common gamma chain (gammac) with the granulocyte/macrophage colony-stimulating factor receptor beta (GM-CSFRbeta) chain is found in mobilized human peripheral blood (MPB) CD34+ hematopoietic progenitors, SCF/Flt3-L primed cord blood (CB) precursors (CBPr CD34+/CD56-), and CD34+ myeloid cell lines, but not in normal natural killer (NK) cells, the cytolytic NK-L cell line or nonhematopoietic cells. We demonstrated, using CD34+ TF1beta cells, which express an interleukin (IL)-15Ralpha/beta/gammac receptor, that within the hybrid receptor, the GM-CSFRbeta chain inhibits the IL-15-triggered gammac/JAK3-specific signaling controlling TF1beta cell proliferation. However, the gammac chain is part of a functional GM-CSFR, activating GM-CSF-dependent STAT5 nuclear translocation and the proliferation of TF1beta cells. The hybrid receptor is functional in normal hematopoietic progenitors in which both subunits control STAT5 activation. Finally, the parental TF1 cell line, which lacks the IL-15Rbeta chain, nevertheless expresses both a functional hybrid receptor that controls JAK3 phosphorylation and a novel IL-15alpha/gammac/TRAF2 complex that triggers nuclear factor kappaB activation. The lineage-dependent distribution and function of these receptors suggest that they are involved in hematopoiesis because they modify transduction pathways that play a major role in the differentiation of hematopoietic progenitors.

Antibodies, Monoclonal↗
PubMed2003

Chemosensitization of myeloma plasma cells by an antisense-mediated downregulation of Bcl-2 protein.

An antisense oligodeoxynucleotide (ODN) complementary to the first six codons of the Bcl-2 mRNA, G3139 (oblimersen sodium; Genasense), has been shown to downregulate Bcl-2 and produce responses in a variety of malignancies including drug-resistant lymphoma. Incubation of ex vivo purified plasma cells from patients with multiple myeloma (MM) with carboxyfluorescein (FAM)-labeled antisense ODNs resulted in a time- and dose-dependent uptake in the cytoplasm and nucleus. No major differences in uptake of Bcl-2 antisense ODNs were observed among patients' samples. Incubation of purified myeloma plasma cells with G3139, but not solvent or reverse polarity control ODNs, resulted in a reduction (>75%) of Bcl-2 mRNA levels after 2 and 4 days, as measured by Real-Time PCR. Treatment with G3139 led to a sequence-specific reduction of Bcl-2 protein levels within 4 days of exposure in 10 out of 11 clinical samples from patients with chemosensitive and multidrug-resistant disease, without significant reduction of alpha-Actin, Bax, Bcl-XL, or Mcl-1 proteins. This resulted in a significantly enhanced sensitivity of the myeloma tumor cells to dexamethasone or doxorubicin-induced apoptosis. G3139 can consistently enter myeloma cells, downregulate the expression of Bcl-2, and enhance the efficacy of myeloma therapy. These data support further clinical evaluation of G3139 therapy in multiple myeloma.

Aged↗
PubMed2003

The hepatocyte growth factor/Met pathway controls proliferation and apoptosis in multiple myeloma.

The evolution of multiple myeloma (MM) depends on complex signals from the bone marrow (BM) microenvironment, supporting the proliferation and survival of malignant plasma cells. An interesting candidate signal is hepatocyte growth factor/scatter factor (HGF), since its receptor Met is expressed on MM cells, while HGF is produced by BM stromal cells and by some MM cell lines, enabling para- or autocrine interaction. To explore this hypothesis, we studied the biological effects of HGF stimulation on MM cell lines and on primary MMs. We observed that Met is expressed by the majority of MM cell lines and by approximately half of the primary plasma cell neoplasms tested. Stimulation of MM cells with HGF led to the activation of the RAS/mitogen-activated protein kinase and phosphatidylinositol 3-kinase/protein kinase B (PI3K/PKB) pathways, signaling routes that have been implicated in the regulation of cell proliferation and survival. Indeed, functional studies demonstrated that HGF has strong proliferative and anti-apoptotic effects on both MM cell lines and primary MM cells. Furthermore, by applying specific signal-transduction inhibitors, we demonstrated that MEK is required for HGF-induced proliferation, whereas activation of PI3K is required for both HGF-induced proliferation and for rescue of MM cells from apoptosis. Taken together, our data indicate that HGF is a potent myeloma growth and survival factor and suggest that the HGF/Met pathway is a potential therapeutic target in MM.

Aged↗
PubMed2002

Bone histomorphometric evaluation of a clinically fused titanium tumour cage in a child.

An intervertebral titanium tumour cage was implanted in a 2-year-old-girl after T11 spondylectomy due to Ewing sarcoma. After 2-years' follow-up without evidence of recurrence, the titanium cage was explanted to correct spinal deformity and to allow normal spinal growth development. Radiological follow-up and surgical exploration at the time of retrieval suggested fusion of the segment. Histologic evaluation, however, demonstrated ingrowth of trabecular bone, but without bridging trabecular bone. The distance between the opposing bone fronts measured 1.5 mm and the viable bone volume (BV/TV) within the cage was 36%. Histologic evaluation demonstrated that bone formation was still an ongoing process in the fusion zone 2 years after implantation.

Child, Preschool↗
PubMed2002

In vitro and in vivo degradation of bioabsorbable PLLA spinal fusion cages.

The in vitro and in vivo degradation of poly-L-lactic acid cages used as an adjunct to spinal arthrodesis was investigated. In the in vitro experiments cages were subjected to aging up to 73 weeks in phosphate-buffered solution (pH 7.4) at 37 degrees C. Inherent viscosity, crystallinity, and mechanical strength were determined at different time points. In the in vivo study, the poly-L-lactic acid cages were packed with bone graft and implanted in the L3-L4 spinal motion segment of 18 Dutch milk goats. At 12, 26, and 52 weeks, the motion segments were isolated and poly-L-lactic acid samples retrieved. On evaluation, the in vivo implanted cages showed an advanced decline in inherent viscosity compared to the cages subjected to in vitro degradation experiments. At 6 months of implantation, the geometrical shape and original height of 10 mm was maintained during 6 months of follow up. This finding fits well with the observation that mechanical strength was maintained for a period of 6 months in vitro. At 12 months, the poly-L-lactic acid cage had been disintegrated into multiple fragments with signs of absorption. Despite the high-load-bearing conditions, the poly-L-lactic acid cage allowed interbody fusion to occur without collapse of the cage.

Absorption↗
PubMed2002

Resorbable cages for spinal fusion: an experimental goat model.

OBJECT: A biomechanical cadaveric study and an in vivo monosegmental spinal fusion study were performed to evaluate a novel bioresorbable poly(L-lactic acid) (PLLA) cage. METHODS: The yield strength of a spinal segment was chosen as the main design parameter for the resorbable cages to be used in a goat model. In a 3-year in vivo study the authors found fusion to be significantly faster and more complete when using PLLA cages compared to titanium cages with the same dimensions. In the PLLA group, the intervertebral grafting height did not change and bone remodeling within the cage was completed 2 years after implantation. In terms of degradation of the PLLA, similar features were observed in vivo and in vitro. CONCLUSIONS: Degradation was almost completed 3 years after implantation. Tissue reaction was mild during the 3-year period.

Absorbable Implants↗
PubMed2002

Resorbable cages for spinal fusion: an experimental goat model.

A biomechanical cadaver study and an in vivo monosegmental spinal fusion study were performed to evaluate a novel bioresorbable poly-L-lactic acid (PLLA) cage. The yield strength of a spinal segment was chosen as the main design parameter for the resorbable cages to be used in a goat model. A 3-year in vivo study revealed a significantly faster and more complete fusion using PLLA cages as compared to titanium cages with the same dimensions. In the PLLA group, the intervertebral grafting height did not change and bone remodeling within the cage was completed 2 years after implantation. In terms of degradation of the PLLA, similar features were observed in vivo and in vitro. Degradation was almost completed 3 years after implantation. Tissue reaction was mild during the 3-year period.

Absorbable Implants↗
PubMed2001

Polyurethane real-size models used in planning complex spinal surgery.

STUDY DESIGN: The application of polyurethane real-size models for planning and performing complex spinal surgery is described. OBJECTIVE: To determine the feasibility of using polyurethane real-size models to plan osteotomies, resections, and designs of custom-made spinal implants in complex spinal surgery. SUMMARY OF BACKGROUND DATA: In selected patients with complex spinal pathology, exact planning of the surgical procedure is not possible using current imaging methods. In these cases, real-size spinal models would be desirable to enhance pre- and perioperative planning by visual and tactile feedback, and to improve the production of custom-made spinal implants. METHODS: A real-size spinal model of six patients was produced from hardened polyurethane foam on the basis of data from contiguous computer tomography slices. In two patients, the models were used to plan correction osteotomies and resections, with the assistance of image-guided surgery in one of the patients. In four patients, the models were used to plan tumor resections and to produce custom-made spinal implants. RESULTS: In all the patients, the surgical procedure could be performed exactly according to the preplanned intervention. The polyurethane real-size models provided essential and additional information by direct visual and tactile feedback. They allowed in vitro testing of custom-made spinal implants with a perfect fit. CONCLUSIONS: Real-size spinal models made from polyurethane foam can be used to provide excellent understanding of the complex spinal pathology in highly selected patients. These models allow complex spinal surgery with a more predictable outcome.

Adolescent↗
PubMed2001

Reconstruction after total en bloc sacrectomy for osteosarcoma using a custom-made prosthesis: a technical note.

STUDY DESIGN: A report of an innovative technique to restore the lumbosacral junction after resection of primary highly malignant osteosarcoma of the sacrum involving the whole sacrum, soft tissues, and adjacent posterior parts of both iliac wings. OBJECTIVES: To describe the planning and design of a custom-made sacral prosthesis, the surgical technique, and clinical and functional outcome of the patient. SUMMARY OF BACKGROUND DATA: Although there have been case reports about reconstruction methods after total sacrectomy, to date, there has not been a reported clinical case of successful reconstruction using an individual designed prosthesis based on a three-dimensional real-sized model. METHODS: A 42-year-old woman was referred with progressive neurologic impairment due to primary osteosarcoma of the sacrum invading surrounding structures. Based on a three-dimensional real-sized model, a detailed surgical plan was developed to assure safe, wide surgical margins. In addition, the model enabled design and testing of a custom-made sacral prosthesis, to provide stable lumbosacral reconstruction. RESULTS: After induction chemotherapy, a staged anteroposterior resection-reconstruction was successfully performed. After surgery, a superficial wound dehiscence was promptly treated. Within 3 weeks after surgery, mobilization began, and the adjuvant chemotherapy was continued. At the 36-month follow-up, the patient was disease free, had a stable, painless spinopelvic junction, and could walk short distances using ankle orthoses and crutches. Radiographs show complete incorporation of the pelvic grafts and unchanged position of the implant. CONCLUSIONS: In planning and performing a total sacrectomy, including substantial parts of iliac wings, a three-dimensional real-sized model offers surgeons distinct advantages. Wide bony resection margins can be drawn on the model, and an individual custom-made prosthesis to re-establish spinopelvic continuity can be designed and tested before the intervention.

Adult↗
PubMed2001

The association between physiological and behavioral pain measures in 0- to 3-year-old infants after major surgery.

To estimate the association between behavioral and physiological pain measures and to identify determinants predicting the level of association, the COMFORT 'behavior' scale, heart rate (HR), mean arterial pressure (MAP), and the variability of HR and MAP (HRV and MAPV) were assessed every 3 hours after major abdominal or thoracic surgery. Subjects were 204 infants aged 0-3 years. The within-subject correlations, using the repeated measures, were 0.37, 0.44, 0.48, and 0.49 for COMFORT 'behavior' with HRV, HR, MAP, and MAPV, respectively. Neonates had lower behavior-physiology correlations than the older infants, due to low pain scores. Pain characteristics significantly predicted the COMFORT 'behavior'-HR/MAP correlations, suggesting that the behavior-physiology correlations increase with increasing pain. The behavior-physiology correlations were not greatly affected by physical condition. These data demonstrate large interindividual differences in behavior-physiology correlations after major surgery in 0- to 3-year-old infants. These differences should be further explored in future research.

Abdomen↗