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Biomedical subjects

H Koning

Publications and source records attributed to H Koning.

At least 19 recordsLinked to original sources
PubMed2003

Diagnosing chronic fatigue syndrome: comparison of a protocol and computerised questionnaires.

BACKGROUND: In the context of outpatient care and within the framework of scientific research, guidelines and measuring instruments have been developed to help improve CFS diagnostics. The purpose of this study was to measure the agreement between the evaluations of chronically fatigued patients by physicians using a CFS protocol and by researchers using computerised questionnaires. METHODS: The sample consisted of 516 patients referred to an internal medicine outpatient clinic with complaints of chronic fatigue. Retrospectively the medical records and the computerised questionnaires were checked separately and compared to see whether the criteria for diagnosis of CFS had been met. In addition, the reasons for not diagnosing CFS were evaluated. RESULTS: Agreement between the physicians' and the researchers' evaluations was 84%. Disagreement mostly concerned severity of fatigue and functional impairment, or premorbid exclusion criteria. A physical cause for the chronic fatigue was only found in 3% of the cases. CONCLUSIONS: For physicians, questionnaire assessment may be complementary to the CFS protocol in optimising the process of diagnosing CFS.

Adult↗
PubMed2002

Brain morphology in antipsychotic-naïve schizophrenia: a study of multiple brain structures.

BACKGROUND: Although brain volume changes are found in schizophrenia, only a limited number of structural magnetic resonance imaging studies have exclusively examined antipsychotic-naïve patients. AIMS: To comprehensively investigate multiple brain structures in a single sample of patients who were antipsychotic-naïve. METHOD: Twenty antipsychotic-naïve patients with first-episode schizophrenia and 20 healthy comparison subjects were included. Intracranial, total brain, frontal lobe, grey and white matter, cerebellar, hippocampal, parahippocampal, thalamic, caudate nucleus and lateral and third ventricular volumes were measured. Repeated-measures analyses of (co)variance were conducted with intracranial volume as covariate. RESULTS: Third ventricle volume enlargement was found in patients compared with the healthy subjects. No differences were found in other brain regions. CONCLUSIONS: These findings suggest that some brain abnormalities are present in the early stages of schizophrenia. Moreover, it suggests that brain abnormalities reported in patients with chronic schizophrenia develop in a later stage of the disease and/or are medication induced.

Adolescent↗
PubMed2001

Focal gray matter density changes in schizophrenia.

BACKGROUND: The view that schizophrenia is a brain disease particularly involving decrements in gray matter is supported by findings from many imaging studies. However, it is unknown whether the (progressive) loss of tissue affects the brain globally or whether tissue loss is more prominent in some areas than in others. METHODS: Magnetic resonance whole brain images were acquired from 159 patients with schizophrenia or a schizophreniform disorder and 158 healthy subjects across a 55-year age span. Gray matter density maps were made and analyzed using voxel-based morphometry. RESULTS: Compared with healthy subjects, decreases in gray matter density were found in the left amygdala; left hippocampus; right supramarginal gyrus; thalamus; (orbito) frontal, (superior) temporal, occipitotemporal, precuneate, posterior cingulate, and insular cortices bilaterally in patients with schizophrenia or schizophreniform disorder. Compared with healthy subjects, increases in gray matter density were exclusively found in the right caudate and globus pallidus in patients with schizophrenia or schizophreniform disorder. A group-by-age interaction for density was found in the left amygdala, owing to a negative regression slope of gray matter density on age in the left amygdala in patients compared with healthy subjects. CONCLUSIONS: Gray matter density is decreased in distinct focal areas in the brains of patients with schizophrenia or schizophreniform disorder. The decreased density in the left amygdala is more pronounced in older patients with schizophrenia.

Adolescent↗
PubMed2001

Percutaneous endoscopic gastrostomy and gastrojejunostomy in psychomotor retarded subjects: a follow-up covering 106 patient years.

BACKGROUND: Whether psychomotor retarded persons should be treated by percutaneous endoscopic gastrostomy (PEG) or by surgical gastrostomy combined with an antireflux procedure is controversial. Therefore, the authors investigated the feasibility of a PEG and enteral feeding in these patients. METHODS: Patients referred from specialized institutions for a PEG placement were assessed extensively by a multidisciplinary team. When considered eligible, age and general condition determined the choice of treatment under general anesthesia (group 1) or conscious sedation (group 2). Patients were followed up after 1 and 7 days, 4 and 12 weeks, and thereafter every 6 to 12 weeks. Data were collected prospectively over a period of 5 years until gastrostomy removal, death, or arrival at the censory date, 6 months after PEG placement. The endpoints were 1) to evaluate the procedure and its complications; 2) to discover barriers that impeded adequate nutrition; and 3) to explore the appropriateness of the choice of PEG or percutaneous endoscopic gastrojejunostomy (PEJ). RESULTS: The procedure was successful in 95% of patients, in every patient in group 1 (35/35; median age, 4.1 years) and in 20 of 23 patients (87%) in group 2 (median age, 22.0 years). There were no procedure-related deaths and no 30-day mortality. Major complications changed from procedure-related problems in the short term (5.4%) to tube-related problems in the long-term (24.1%). Nausea and vomiting interfered with adequate feeding mainly in young children, but dietary adjustments alleviated the symptoms and ensured an adequate intake. The choice of a PEG was incorrect in four patients: surgery was needed twice and two PEGs had to be converted into a PEJ. All seven primarily indicated PEJs seemed justified and of temporary need in five. CONCLUSIONS: In severely disabled patients, a PEG and adequate enteral nutrition is feasible in the setting of a multidisciplinary approach and protocol-wise follow-up. Yet, anatomic deformities and restricted pulmonary function rendered the procedure more difficult. In cases with obvious aspiration or gastroesophageal reflux, a PEJ combined with acid suppression and prokinetic drugs may be tried before surgery.

Adolescent↗
PubMed2001

Clinico-immunological heterogeneity in Comèl-Netherton syndrome.

BACKGROUND: Comèl-Netherton syndrome (CN) is characterized by atopic-eczema-like skin abnormalities combined with linear ichthyotic lesions, hair shaft abnormalities and atopy with high IgE levels. OBJECTIVE: Five children with CN are described. In 2 of the 3 CN patients still alive, analysis of cytokines regulating IgE synthesis was performed. METHODS: In peripheral blood mononuclear cells and cultures of purified T cells, mRNA expression and protein production of interleukin 4 (IL-4), IL-13, IL-5 and interferon gamma were analysed. The results were compared with the values in age-matched atopic dermatitis patients and healthy children. RESULTS: The 5 CN patients showed striking differences in disease severity and evolution. Marked differences were found in several cytokines in the 2 analysed CN patients. Low percentages of natural killer cells were observed in both CN patients. CONCLUSION: The regulation of IgE production in patients with CN is varied and complex. The CN patients were heterogeneous in terms of Th2 skewing.

Child↗
PubMed2000

Differential expression of sphingolipids in MRP1 overexpressing HT29 cells.

We have obtained a novel multidrug resistant cell line, derived from HT29 G(+) human colon carcinoma cells, by selection with gradually increasing concentrations of the anti-mitotic, microtubule-disrupting agent colchicine. This HT29(col) cell line displayed a 25-fold increase in colchicine resistance and exhibited cross-resistance to doxorubicin, VP16, vincristine and taxol. Immunoblotting, combined with RT-PCR showed that the multidrug resistance phenotype was conferred by specific overexpression of the multidrug resistance protein 1. Confocal scanning laser microscopy revealed that multidrug resistance protein 1 specifically localized in the plasma membrane of HT29(col) cells. In a functional assay, using the fluorescent multidrug resistance protein 1 substrate 5-carboxyfluorescein, an increased efflux activity of HT29(col) cells was measured, as compared to the wild-type HT29 G(+) cells. MK571, a specific inhibitor of multidrug resistance protein 1, blocked the 5-carboxyfluorescein efflux, but only partially reversed resistance to colchicine, indicating that additional multidrug resistance mechanisms operate in HT29(col) cells. In conclusion, these results show for the first time overexpression of a functional multidrug resistance protein 1 under colchicine pressure, indicating that colchicine is not a P-glycoprotein-specific substrate. Colchicine-induced overexpression of multidrug resistance protein 1 is accompanied by a changed sphingolipid composition, i.e., enhanced levels of glucosylceramide and galactosylceramide. In addition, ceramide, a lipid messenger molecule involved in apoptosis-related signal transduction processes, was much more abundant in HT29(col) cells, which is indicative of a stress response.

ATP-Binding Cassette Transporters↗
PubMed1999

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) induce hepatic expression of the phospholipid translocase mdr2 in rats.

BACKGROUND & AIMS: Biliary cholesterol secretion is coupled to that of phospholipids in a process controlled by mdr2 P-glycoprotein activity and bile salt secretion. Statins, the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, have been shown to affect hepatobiliary lipid secretion in rats. The aim of this study was to relate the effects of statins on bile formation to the expression of mdr2 and other hepatic adenosine triphosphate-dependent transport proteins involved in bile formation in rats. METHODS: Rats received simvastatin- or pravastatin-containing chow continuously for 5 days. In one group of rats, simvastatin treatment was withdrawn 9-12 hours before the end of the experiment to induce biliary cholesterol hypersecretion (rebound). Bile and liver tissue were collected for lipid analysis, and hepatic messenger RNA (mRNA) and protein levels were studied by reverse-transcription polymerase chain reaction, immunoblotting, and immunohistochemistry. RESULTS: Simvastatin feeding did not alter biliary bile salt secretion. Secretion of phospholipids and cholesterol was stimulated by 74% and 90%, respectively, in the simvastatin-continuous group and by 72% and 235%, respectively, in the rebound group compared with controls. mdr2 mRNA levels increased only in the continuous group. mdr2 protein levels increased in both simvastatin-fed groups. Induction was most pronounced in periportal hepatocytes. mdr1b mRNA levels were moderately increased in both simvastatin-fed groups. Levels of other hepatic transport proteins did not change. Similar results were obtained in pravastatin-fed rats. CONCLUSIONS: Statins increase expression of mdr2 and mdr1b in rats, revealing a novel effect of these commonly used drugs.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1999

Percutaneous endoscopic gastrostomy and gastrojejunostomy: a critical reappraisal of patient selection, tube function and the feasibility of nutritional support during extended follow-up.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a generally accepted procedure, but the appropriateness of patient selection and the justification of jejunal feeding have not been systematically investigated. Also, a critical appraisal of the applicability and tolerance of nutritional support in the immediate postinsertion period and during prolonged outpatient care is lacking. METHODS: Prospectively collected data in adult and pediatric patients during a period of 7 years were analyzed. Follow-up data were available at days 1, 7 and 28 and thereafter every 6 to 12 weeks until gastrostomy removal, death or the conclusion of the study. RESULTS: A PEG was successfully positioned in 268 of the 286 referred patients (94%). A jejunal tube through the PEG (JETPEG) was placed beyond the duodenojejunal ligament in 38 patients. Procedure-related mortality was 1%, 30-day outpatient mortality 6.7%. Total follow-up was 295 patient-years with an overall mortality of 53% (PEG 53%; JETPEG 50%). Both major (8.4%) and minor (24.0%) procedure-related complications in the first 28 days consisted merely of (infectious) wound problems. In prolonged follow-up, the complications were more tube-related. The durability of the tube in surviving patients with a PEG or JETPEG in situ was a median of 495 days (range 162 to 1732 days). Tube dysfunction because of clogging, porosity and fracture occurred after a median of 347 days (range 9 to 1123 days). Nausea, vomiting, bloating and dumping interfered with feeding during the first week and during extended follow-up. Intrajejunal feeding was associated with dumping and diarrhea. In retrospect, the anticipated need of 4 weeks of enteral nutrition was not met in 9.0%. The extension of a PEG into a JETPEG was thought inappropriate in 23.7%. In the remainder, a 91% reduction in aspiration justified its use. The tube life span was equal to or greater than that of a PEG, despite tube dysfunction in 26.8%. CONCLUSIONS: Proper selection of patients for a PEG, i.e., those with an anticipated need of greater than 4 weeks of enteral nutrition, is a challenge. Notwithstanding an increased rate of tube dysfunction, well-selected patients may benefit from a JETPEG. Follow-up is mandatory because many patients might have become malnourished or underfed while on tube feeding, mainly because of GI intolerance.

Adolescent↗
PubMed1999

Glutathione S-conjugate transport in hepatocytes entering the cell cycle is preserved by a switch in expression from the apical MRP2 to the basolateral MRP1 transporting protein.

The multidrug resistance protein MRP1 and its isoform MRP2 are involved in ATP-dependent glutathione S-conjugate transport and have similar substrate specificities. MRP2 mediates hepatic organic anion transport into bile. The physiological function of MRP1 in hepatocytes is unknown. Previous results show that MRP1 expression is low in quiescent hepatocytes but increased after SV40 large T antigen immortalization, suggesting a relationship with cell proliferation. Therefore, we determined mrp1 and mrp2 expression in rat hepatocytes in relation to the cell cycle. By varying cell density we obtained cultures that are mainly in G1 (high density) or have progressed into the S-phase or beyond (low density). In both cultures mrp1 mRNA and protein levels are increased, concomitantly with the disappearance of mrp2. This switch from mrp2 to mrp1 occurs in the G1 phase of the cell cycle and is associated with a decreased cell polarity. Mrp1 is located on lateral membranes or on intracellular vesicles, depending on whether cell-cell contact is established. In both locations mrp1 contributes to cellular glutathione S-conjugate efflux and protects against oxidative stress-inducing quinones. We conclude that a switch in expression from the apically located mrp2 to the basolaterally located mrp1 preserves glutathione S-conjugate transport in hepatocytes entering the cell cycle and protects against certain cytotoxic agents.

ATP-Binding Cassette Transporters↗
PubMed1998

Up-regulation of the multidrug resistance genes, Mrp1 and Mdr1b, and down-regulation of the organic anion transporter, Mrp2, and the bile salt transporter, Spgp, in endotoxemic rat liver.

Endotoxin-induced cholestasis is mainly caused by an impaired canalicular secretion. Mrp2, the canalicular multispecific organic anion transporter, is strongly down-regulated in this situation, and canalicular bile salt secretion is also reduced. We hypothesized that other adenosine triphosphate-binding cassette (ABC) transporters may compensate for the decreased transport activity to protect the cell from cytokine-induced oxidative damage. Therefore, we examined the expression of ABC-transport proteins in membrane fractions of whole liver and of isolated hepatocytes of endotoxin-treated rats and performed reverse-transcriptase polymerase chain reaction (RT-PCR) on mRNA isolated from these livers. In addition, the localization of these transporters was examined using confocal scanning laser microscopy. By 6 hours after endotoxin administration, we found a clear increase of mrp1 mRNA and protein, whereas mrp2 mRNA and protein were decreased. This was confirmed in isolated hepatocytes. In addition, mdr1b mRNA was strongly increased, whereas mdr1a and mdr2 mRNA did not change significantly. Both the mRNA and protein levels of the sister of P-glycoprotein (spgp), the recently cloned bile salt transporter, decreased. After endotoxin treatment, the normally sharply delineated canalicular staining of mrp2 and spgp had changed to a fuzzy pattern, suggesting localization in a subapical compartment. We conclude that endotoxin-induced cholestasis is caused by decreased mrp2 and spgp levels, as well as an abnormal localization of these proteins. The simultaneous up-regulation of mrp1 and mdr1b may confer resistance to hepatocytes against cytokine-induced metabolic stress.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Levels of soluble intercellular adhesion molecule-1, soluble E-selectin, tumor necrosis factor-alpha, and soluble tumor necrosis factor receptor p55 and p75 in atopic children.

During inflammation, membrane expression of adhesion molecules and tumor necrosis factor (TNF)-receptors (TNF-R) are increased, and soluble forms of these molecules are released. This study analyzed plasma levels of sICAM-1 and sE-selectin as well as TNF-alpha, sTNF-R55, and sTNF-R75 in nonallergic (NAA) and allergic asthma patients (AA), atopic dermatitis patients (AD), and healthy children (HC) by ELISA. Plasma levels of sICAM-1, sE-selectin, and sTNF-R, but not TNF-alpha, were detectable, but were not significantly different between the patient groups and healthy children. In the AA group, a significant correlation (rs = 0.78, P = 0.008) was found between sICAM-1 and sE-selectin levels. Furthermore, a significant correlation was found between sTNF-R55 and sTNF-R75 levels in the AA group (rs = 0.70, P = 0.025) and in the AD group (rs = 0.69, P = 0.027). In AD patients, a significant correlation was observed between sE-selectin and the disease severity, as measured by the SCORAD index (rs = 0.73, P = 0.038). Our data demonstrate that plasma levels of sICAM-1, sE-selectin, TNF-alpha, sTNF-R55, and sTNF-R75 were not different between atopic and nonatopic children during a stable phase of the disease. In AD patients, levels of sE-selectin seemed to be related to clinical severity of the disease.

Age Factors↗
PubMed1997

T cell subsets and cytokines in allergic and non-allergic children. I. Analysis of IL-4, IFN-gamma and IL-13 mRNA expression and protein production.

Interleukin 4 (IL-4) and IL-13 are key cytokines inducing switching to immunoglobulin E (IgE), whereas interferon gamma (IFN-gamma) acts inhibitory on this process. We analysed whether differences existed in IL-4, IFN-gamma and IL-13 mRNA expression and protein production between T cells of children with allergic and non-allergic asthma, atopic dermatitis and health control children. IL-4 mRNA expression was increased in stimulated T cells of children with allergic asthma and atopic dermatitis, but not in those with non-allergic asthma as compared with healthy controls. Thus the increase in IL-4 expression can be considered as an underlying mechanism of the allergic disease process and not so much of the asthmatic state of the children. In unstimulated T cells of children with atopic dermatitis increased IFN-gamma mRNA expression with a reduced IFN-gamma protein production was found, indicating a post-translational defect in IFN-gamma. Differences in IL-13 expression between the groups were not significant, but IL-13 was significantly correlated with the height of the radio-allergo-sorbent test (RAST) class and with the severity scoring of atopic dermatitis (SCORAD) index. This indicates the clinical relevance of IL-13 for the degree of allergen-specific sensitization and severity of atopic dermatitis. In conclusion, the imbalance in IL-4 and IFN-gamma secretion in patients with atopic dermatitis may reflect general T cell activation in the presence of an intrinsic defect of IFN-gamma secretion.

Asthma↗
PubMed1997

T cells subsets and cytokines in allergic and non-allergic children. II. Analysis and IL-5 and IL-10 mRNA expression and protein production.

Interleukin 5 (IL-5) has an enhancing effect on IL-4 induced immunoglobulin E (IgE) synthesis. Furthermore, IL-5 plays an important role in the differentiation, recruitment, activation and survival of eosinophils. IL-10 has a downmodulating effect on interferon gamma (IFN-gamma) production and can exert strong anti-inflammatory activities. Therefore, we analysed whether differences were present in IL-5 and IL-10 mRNA expression and protein production between T cells of children with allergic and non-allergic asthma, atopic dermatitis and healthy control children. We demonstrated significant increases in IL-5 mRNA expression and protein production in different T cell fractions of children with allergic and non-allergic asthma and children with atopic dermatitis as compared to healthy controls. This indicates that IL-5 is not only involved in allergy, but also plays a role in the inflammatory process of non-allergic asthma. Interestingly, IL-10 mRNA expression by purified T cells of children with allergic and non-allergic asthma and children with atopic dermatitis was strongly decreased as compared with that of healthy controls. In the peripheral blood mononuclear cell (PBMC) fraction, IL-10 mRNA expression was comparable between the four groups. We hypothesize that this decreased T cell derived IL-10 expression results in a lack of immunosuppression of the inflammatory process in these diseases. However, a role of monocyte derived IL-10 cannot be ruled out.

Asthma↗
PubMed1997

Increased levels of the multidrug resistance protein in lateral membranes of proliferating hepatocyte-derived cells.

BACKGROUND & AIMS: The multidrug resistance protein (MRP) functions as an organic anion efflux carrier. Recent studies suggest that hepatocytes contain two mrp homologues, named mrp1 and mrp2, localized on the lateral and canalicular membrane, respectively. The aim of this study was to evaluate the role of MRP1. Protein levels and localization of MRP1 in human hepatocytes, HepG2 hepatoma cells, and SV40 large T antigen-immortalized human hepatocytes were studied. METHODS: Using specific antibodies, MRP1 protein levels and cellular localization were examined by Western blotting and fluorescence confocal microscopy, respectively. In addition, a fluorescent substrate, glutathione-methylfluorescein, was used to measure plasma membrane transport activity and to observe intracellular transport activity. RESULTS: The level of MRP1 in normal hepatocytes is very low. In contrast, MRP1 is highly increased in both HepG2 and immortalized hepatocytes. In these cells MRP1 is localized in lateral membranes of adjacent cells. Plasma membrane staining is absent in separate cells. Glutathione-methylfluorescein is transported in the medium and intracellular vesicles. CONCLUSIONS: MRP1 protein level is greatly increased in the lateral membrane of proliferating hepatocyte-derived cells. The presence of a lateral domain seems necessary for plasma membrane localization. These results suggest that MRP1-mediated organic anion transport is important in proliferating hepatocytes, but not in quiescent cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Development of immune functions related to allergic mechanisms in young children.

The newborn immune system differs quantitatively and functionally from that of adults. Development of the immune system has important implications for childhood diseases. The immaturity of the immune system in the first years of life may contribute to failure of tolerance induction and in the development of allergic disease. T cell function is diminished, especially the capacity to produce cytokines; production of interferon (IFN)-gamma, and IL-4 is strongly reduced. IFN-gamma has been found to be even lower in cord blood of newborns with a family history of atopy. Differences in other cell types (natural killer cells, antigen-presenting cells, and B cells) could also play a role in the development of allergic disease. Current data suggest that irregularities in IgE synthesis, helper T cell subsets (Th1, Th2, CD45RA, and CD45RO), cytokines (IL-4, IFN-gamma), and possibly other cell types may play a role in the development of allergy in childhood. Moreover, the role of cell surface molecules, like co-stimulatory molecules (CD28, CD40L), activation markers (CD25), and adhesion molecules (LFA-1/ICAM-1, VLA-4/ VCAM-1) is also discussed. These variables are modulated by genetic (relevant loci are identified on chromosome 5q, 11q, and 14) and environmental forces (allergen exposure, viral infections, and smoke). The low sensitivity of current predictive factors for the development of allergic diseases, such as cord blood IgE levels, improves in combination with family history and by measurement of in vitro responses of lymphocytes and skin reactivity to allergens. New therapeutic approaches are being considered on the basis of our current understanding of the immunopathology of allergic disease, for instance cytokine therapy and vaccination with tolerizing doses of allergen or peptides.

Child↗