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Kjell Tullus

Publications and source records attributed to Kjell Tullus.

At least 19 recordsLinked to original sources
PubMed2006

Clinicopathological correlations of paediatric lupus nephritis.

The International Society of Nephrology and Renal Pathology Society Working Group revised the histopathological classification of lupus nephritis (LN) in 2003. We studied the clinical outcome of 39 children (85% female) aged 3.3-18.0 (median 13.7) years who underwent 49 percutaneous renal biopsies at 0.1-7.8 (median 1.0) years from diagnosis of systemic lupus erythematosus (SLE) at our centre over 10 years. All renal biopsies were reviewed and reclassified according to the new criteria by one histopathologist: 2%, 13%, 15%, 51% and 20% of all cases were classes I-V, respectively (with no cases of class VI LN) and 12% overlap cases (4% classes III and V, 8% classes IV and V). Patients were followed up for 1.3-15.4 (median 5.5) years with renal and overall survival rates of 90% and 92%, respectively. Half of the children with LN have features of class IV LN, with diffuse global (class IV-G) LN associated with the worst clinical outcome and the three most severe cases of chronic renal failure with estimated glomerular filtration rates (GFRs) <25 ml/min per 1.73 m(2) in patients with diffuse global sclerosing [class IV-G(C)] LN. The new classification allows expanded histopathological grading of LN with further delineation of classes III and IV with activity and chronicity indices.

Adolescent↗
PubMed2006

Childhood vasculitis and plasma exchange.

INTRODUCTION: A retrospective review of therapeutic plasma exchange (TPE) for vasculitis of any form during the period 1993-2003 was carried out in our unit. SUBJECTS AND METHODS: The case histories of 32 children undergoing TPE were analysed to determine short-term outcome. The vasculitides consisted of polyarteritis nodosa (PAN), ANCA-associated vasculitis (AAV) [encompassing Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA)/idiopathic crescentic nephritis (ICN)], Henoch-Schönlein purpura (HSP) and non-classified vasculitis (NCV). RESULTS: All children with PAN (n=5) had a good response to treatment except for one with gastro-intestinal symptoms. One child was treated for crescentic nephritis, with 42% crescents seen on biopsy. The estimated glomerular filtration rate (eGFR) (Schwartz formula) for this child improved from 81 to 130 ml/min/1.73 m(2) post-treatment. Inflammatory markers decreased immediately following TPE and were maintained at the lower level for all the children. Ten children (n=12) with AAV received treatment for renal manifestations. Median creatinine clearances improved from 29 ml/min/1.73 m(2) (p<0.01) pre-treatment to 62 ml/min/1.73 m(2) (p<0.01) immediately following TPE and 69 ml/min/1.73 m(2) at 2 months post-TPE (p<0.01). Four children required dialysis; one child remained dialysis-dependent and one child progressed to chronic renal failure. Inflammatory markers decreased following TPE. All of the children with HSP (n=5) were treated for crescentic nephritis. Two regained normal renal function, and one became dialysis-dependent later. Most of the children with NCV (n=10) presented with CNS or general vasculitic features, with the greatest benefit for CNS symptoms. CONCLUSIONS: In our experience TPE appears to be of benefit during the acute phase of illness, especially in children with organ-specific disease.

Adolescent↗
PubMed2006

Time to screen for proteinuria?

UNLABELLED: Screening for proteinuria in childhood is performed in some countries but remains a controversial subject. During the last decade, a greater understanding of the importance of proteinuria for the long-term prognosis of children with renal diseases has been gained. Exciting new data also show that proteinuria is a prognostic factor for long-term cardiovascular outcome. CONCLUSION: In my opinion, there are still not strong enough reasons to support the routine screening of healthy children for proteinuria.

Cardiovascular Diseases↗
PubMed2006

Angioplasty for renovascular hypertension in children: 20-year experience.

OBJECTIVE: Our aim was to evaluate the clinical outcomes, safety, and efficacy of percutaneous transluminal angioplasty for renovascular hypertension in children. METHODS: A retrospective review of data for all children with renovascular hypertension who underwent percutaneous transluminal angioplasty at a single center between 1984 and 2003 was performed. Patients with renal transplants and inflammatory multisystem diseases were excluded. RESULTS: Thirty-three children, 1.9 to 17.9 years of age (median: 10.3 years), underwent renal angioplasty and/or stenting. Underlying syndromes were present in 10. On angiograms, 16 had bilateral renal artery stenosis, 15 intrarenal disease, 8 aortic stenosis, and 7 cerebrovascular disease. Forty-eight percutaneous transluminal angioplasty procedures were performed, including 15 stenting procedures. There was a high rate of restenosis after stenting (7 of 19 cases, compared with 2 of 27 cases after balloon dilation). Outcomes were cured (ie, blood pressure normal without treatment) for 9 patients, improved blood pressure with same or reduced treatment for 7, blood pressure maintained in >95th percentile because of cerebrovascular disease for 2, no change in blood pressure despite technical success for 10, and technical failure for 5. Blood pressure control improved in 11 of 13 children who had main renal artery disease alone and in 6 of 20 with associated intrarenal disease or stenoses in other vascular beds. There was 1 procedure-related death and 5 minor complications. CONCLUSIONS: Angioplasty produced clinically worthwhile improvement for approximately 50% of patients. High incidence rates of extrarenal involvement and intrarenal disease and a high restenosis rate after stenting accounted for poor blood pressure control in the rest.

Adolescent↗
PubMed2005

B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus.

OBJECTIVE: To determine the safety and efficacy of B lymphocyte depletion therapy in patients with refractory childhood-onset systemic lupus erythematosus (SLE). METHODS: Seven patients (4 of whom were female), ages 7.7-16.1 years (median 14.8 years) with active SLE that was resistant to standard immunosuppressive agents were treated with B cell depletion. During a 2-week period, patients received two 750-mg/m2 intravenous infusions of rituximab, with intravenous cyclophosphamide (if they had not previously received this treatment) and high-dose oral corticosteroids. RESULTS: Patients were followed up for a median of 1.0 years, and no serious adverse effects were noted. In all patients, the clinical symptoms and signs for which rituximab therapy was initiated were improved. There was significant improvement in the British Isles Lupus Assessment Group global scores, from a median score of 22 (range 14-37) at baseline to a median score of 6 (range 4-11) at followup (P = 0.002). In 2 patients with severe multisystem and life-threatening disease unresponsive to standard therapy (including plasma exchange), renal replacement therapy was successfully withdrawn following B cell depletion therapy. These 2 patients have subsequently shown further significant improvement in renal function and proteinuria. CONCLUSION: This open-label study demonstrates that targeted B cell depletion therapy can be a safe and efficacious addition to therapy with standard immunosuppressive agents in patients with refractory childhood SLE. The drugs used for treatment of childhood SLE need to be the most effective, least toxic agents, allowing normal growth and development.

Adolescent↗
PubMed2004

Retrospective study of plasma exchange in children with systemic lupus erythematosus.

A retrospective review of patients was conducted to evaluate the short-term effect of therapeutic plasma exchange (TPE) in children with active systemic lupus erythematosus (SLE). Between April 1984 and March 2003, 22 children underwent 112 TPE sessions. The median number of daily, double-volume sessions was 6 (range 1-16). Plasma exchange was performed by centrifugation, using 4.5% albumin with fresh-frozen plasma as required. All children were receiving standard immunosuppressive therapy. The predominant clinical features that led to TPE were categorised into systems and outcome was evaluated according to clinical improvement or lack of it. There was benefit for central nervous system and pulmonary manifestations (10 cases, 11 episodes). Of 8 children treated for renal manifestations, 6 achieved good outcomes. Two children became dialysis dependent despite treatment; however, both had been successfully treated with TPE before. Five children received more than one course of TPE. No child died during the procedure and major complications were few. Our data show that TPE can be used as adjunctive therapy in childhood SLE with few complications. Outcome is difficult to measure but in our experience, during the acute phase of illness, TPE appears to be of benefit.

Adolescent↗
PubMed2004

Tissue inhibitor of metalloproteinase 1 activates normal human granulocytes, protects them from apoptosis, and blocks their transmigration during inflammation.

Urinary levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) higher than those of matrix metalloproteinase 9 (MMP-9) during acute pyelonephritis have previously been associated with a higher degree of acute inflammation and of postinfective renal scarring. The aim of the present study was to evaluate possible mechanisms by which TIMP-1 could affect the scarring process already during the acute phase of inflammation. The growth of Escherichia coli, bactericidal activity of fresh human blood, and respiratory burst, spontaneous apoptosis, and trans-basement membrane migration of normal human granulocytes were studied in vitro in the presence of different concentrations of recombinant human TIMP-1. To imitate the "normal" environment during inflammation in the kidney, granulocytes were also incubated with a conditioned medium from E. coli-stimulated renal epithelial cells. In order to compare our data with the in vivo situation, blood and urinary leukocyte levels were analyzed for 40 children with acute pyelonephritis, together with urinary MMP-9 and TIMP-1 levels. TIMP-1 at a concentration of 500 ng/ml increased the bactericidal activity of blood, increased the respiratory burst of granulocytes, decreased phosphatidylserine exposure and caspase 3 activity, which are features of spontaneous apoptosis, and inhibited granulocyte transmigration. Moreover, in the patients with pyelonephritis, MMP-9/TIMP-1 ratios in urine correlated with the degree of leukocyte transmigration. Thus, our data suggest that TIMP-1 specifically blocks the transmigration of granulocytes into urine. Entrapped and activated granulocytes, protected from apoptosis, might excessively destroy renal parenchyma and thus contribute to the pathogenesis of renal scarring following acute pyelonephritis.

Apoptosis↗
PubMed2003

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in acute pyelonephritis and renal scarring.

The aim of the present study was to elucidate the role of matrix metalloproteinase-9 (MMP-9), and its main inhibitor tissue inhibitor of metalloproteinases-1 (TIMP-1), in acute pyelonephritis and the process of renal scarring. Urine samples from 40 children with acute pyelonephritis, 16 children at 6-wk follow-up and 15 children with nonrenal fever were analyzed using ELISA. MMP-9 and TIMP-1 levels were compared with the outcome of pyelonephritis as measured by renal static scintigraphy. A mouse model of acute ascending pyelonephritis was used to localize the sites of production and the kinetics of MMP-9 and TIMP-1 using immunohistochemistry and ELISA. Human renal epithelial A498 cells, primary mesangial cells and monocytic THP-1 cells were stimulated by Escherichia coli. MMP-9 and TIMP-1 mRNA was analyzed by reverse transcription-PCR (RT-PCR) and protein production by ELISA. We demonstrate a significant increase of MMP-9 and TIMP-1 in the urine of children with acute pyelonephritis. Both proteins were produced mainly by leukocytes, and TIMP-1 also by resident kidney cells. Cells reacted differently after stimulation by bacteria. In mesangial cells and monocytes a decreased constitutive TIMP-1 production was found, which was in contrast to epithelial cells. Out of 40 children with pyelonephritis, 23 had higher urinary TIMP-1 than MMP-9 levels. These children had significantly more severe changes in both acute and follow-up scintigraphy scans indicating higher degree of acute tissue damage and renal scarring. Thus, our findings suggest an association between TIMP-1 and the process of renal scarring.

Acute Disease↗
PubMed2002

Activation of macrophage nuclear factor-kappa B and induction of inducible nitric oxide synthase by LPS.

BACKGROUND: Chronic lung disease (CLD) of prematurity is a major problem of neonatal care. Bacterial infection and inflammatory response have been thought to play an important role in the development of CLD and steroids have been given, with some benefit, to neonates with this disease. In the present study, we assessed the ability of lipopolysaccharide (LPS) to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS) and activate nuclear factor-kappaB (NF-kappaB) in vitro. In addition, we investigated the impact of dexamethasone and budesonide on these processes. METHODS: Griess reaction was used to measure the nitrite level. Western blot and a semi-quantitative RT-PCR were performed to detect iNOS expression. Electrophoretic mobility shift assay (EMSA) was performed to analyze the activation of NF-kappaB. RESULTS: We found that LPS stimulated the rat alveolar macrophages to produce NO in a dose (>or=10 ng/ml) and time dependent manner (p < 0.05). This effect was further enhanced by IFN-gamma (>or=10 IU/ml, p < 0.05), but was attenuated by budesonide (10(-4)-10(-10) M) and dexamethasone (10(-4)-10(-6) M) (p < 0.05). The mRNA and protein levels of iNOS were also induced in response to LPS and attenuated by steroids. LPS triggered NF-kappaB activation, a mechanism responsible for the iNOS expression. CONCLUSION: Our findings imply that Gram-negative bacterial infection and the inflammatory responses are important factors in the development of CLD. The down-regulatory effect of steroids on iNOS expression and NO production might explain the beneficial effect of steroids in neonates with CLD.

Animals↗
PubMed2002

Ureaplasma urealyticum induces apoptosis in human lung epithelial cells and macrophages.

Chronic lung disease (CLD) of prematurity remains a significant cause of morbidity among premature infants. It is a multifactorial disorder and characterized by an early increased number of neutrophils and alveolar macrophages, with later architectural epithelial and endothelial cell damage. Recently, apoptosis of type 2 pneumocytes in the lung of preterm neonates with acute and chronic lung disease has been examined and apoptosis of mesenchymal cells was detected in the chronic stage of bronchopulmonary dysplasia. Infection and inflammatory responses in the lungs play important roles. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated. We found that U. urealyticum induced apoptosis in human type II lung epithelial cells (A549 cell line) and macrophages (derived from human monocytic cell line THP-1) by measuring the outer leaflets translocation of phosphatidylserine (flow cytometry analysis and fluorescence microscopy assessment), DNA fragmentation analysis, cell morphology changes such as diminution in cell volume, increased cytoplasmic staining, and nuclear pyknosis (hematoxylin and eosin staining) and viable counting (trypan blue exclusion). Anti-TNF-alpha monoclonal antibody partially protected the macrophages from undergoing apoptosis after infection with U. urealyticum. Our findings imply that U. urealyticum might be involved in impairing lung structure and host immune response during the development of CLD.

Antibodies, Monoclonal↗
PubMed2002

Induction of human macrophage vascular endothelial growth factor and intercellular adhesion molecule-1 by Ureaplasma urealyticum and downregulation by steroids.

Chronic lung disease (CLD) remains a major cause of morbidity for the prematurely born infant. The pathogenesis of CLD is complex and has not been defined entirely. Infection and lung inflammatory events have been thought to play a key role in the development of CLD. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated and steroids produce some improvement in neonates with this disease. The aim of this study was to investigate if U. urealyticum could stimulate macrophages to produce vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) in vitro, which are potentially associated with both early and later pathological changes in the lung during the development of CLD. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (>/=4 x 10(7) color-changing units/ml) stimulated human macrophages (phorbol 12-myristate 13-acetate-differentiated THP-1 cell line) to produce VEGF and soluble ICAM-1 in a dose-dependent manner (p < 0.05) measured by ELISA. Likewise, cell surface ICAM-1 (CD54) measured by flow cytometry was increased after stimulation with U. urealyticum. This effect was attenuated by budesonide and dexamethasone (p < 0.05). The mRNA expressions of VEGF and ICAM-1 detected by a semi-quantitative reverse transcriptase polymerase chain reaction were also induced in response to U. urealyticum and inhibited by the steroids (p < 0.05). The expression of ICAM-1 was reduced by 85.5% when the TNF-alpha production was neutralized with an anti-TNF-alpha antibody. Our findings imply that U. urealyticum might be involved in the development of CLD of prematurity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Epidemiologic typing of international collections of Klebsiella spp.: computerized biochemical fingerprinting compared with serotyping, phage typing and pulsed-field gel electrophoresis.

OBJECTIVE: The Phene Plate (PhP) biochemical fingerprinting system is based on measurements of the kinetics of selected biochemical reactions performed in microtiter plates, and computerized data-processing. This study compared the performance of the PhP system as an epidemiologic tool with other commonly used typing systems. METHODS: PhP typing was applied to 107 nosocomial Klebsiella spp. isolates from 10 collections, mostly representing outbreaks. The results were compared with those obtained by capsular (K) serotyping, phage typing and, for a subset of isolates (n=33), pulsed-field gel electrophoresis (PFGE). RESULTS: Clusters of identical or closely related isolates based on serotype, phage type, PhP type and PFGE type were found in most collections. The typeability was 100%, 95%, 94% and 68% for PhP, K, PFGE and phage typing, respectively. The agreement between the typing methods was high (88-96%). The discriminatory power was high for PhP and PFGE (diversity index 0.95 and 0.97, respectively), but lower for phage typing (diversity index 0.91) and K typing (diversity index 0.87). CONCLUSIONS: Like serotyping and PFGE, PhP typing is useful in studies of the nosocomial epidemiology of Klebsiella spp. Combining PhP typing with PFGE or K typing rarely yielded additional information when comparing isolates within each collection, but PFGE sometimes discriminated between isolates of similar PhP type derived from different collections.

Journal Article↗