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P Lahdenne

Publications and source records attributed to P Lahdenne.

At least 19 recordsLinked to original sources
PubMed2006

Impact of anti-TNF treatment on growth in severe juvenile idiopathic arthritis.

OBJECTIVES: To evaluate the impact of anti-tumour necrosis factor (TNF) treatment on growth and to identify the predictors for the change in growth in severe juvenile idiopathic arthritis (JIA). METHODS: Data from 71 JIA patients (43 on etanercept, 28 on infliximab) were reviewed two years before and two years on the anti-TNF treatment. The patients had polyarticular disease course (48 polyarthritis, 19 extended oligoarthritis, two systemic arthritis, and two enthesitis related arthritis). At the initiation of the anti-TNF treatment, their mean age was 9.6 years and the mean duration of JIA, 5.7 years. RESULTS: In the patients with delayed growth before anti-TNF treatment (n = 53), the growth velocity, measured as the change in height standard deviation score, accelerated +0.45 (95% confidence interval, 0.33 to 0.56) (p<0.001) during the anti-TNF treatment. In the patients with normal or accelerated growth before anti-TNF treatment (n = 18), the change in growth velocity was +0.05 (0.07 to 0.16) (p = 0.39). At two years on anti-TNF treatment, the growth velocity between these two groups was similar. No difference was found between the patients treated with etanercept or infliximab. A decelerating growth rate before the anti-TNF treatment was the strongest predictor for the observed increase in the growth velocity. The change in the inflammatory activity remained a significant predictor of the growth velocity even after the decrease in glucocorticoid dose was taken into account. CONCLUSIONS: In the treatment of polyarticular JIA, the anti-TNF treatment not only suppresses inflammation but also restores growth velocity.

Adolescent↗
PubMed2005

PRINTO/PRES international website for families of children with rheumatic diseases: www.pediatric-rheumatology.printo.it.

OBJECTIVE: To prepare a website for families and health professionals containing up to date information about paediatric rheumatic diseases (PRD). METHODS: Firstly, paediatric rheumatology centres and family self help associations were surveyed to characterise current clinical practice of physicians providing care for children with PRD, research activities, and training facilities of each centre. Secondly, international consensus was reached on the content of the website. Finally, the website was developed and the texts translated. RESULTS: The web page contains three main sections: (a) description for families of the characteristics of 15 PRD; (b) list of paediatric rheumatology centres; (c) contact information for family self help associations. A version for 45 countries in 52 languages (with another three in progress) is now available on the web. 291 surveys from 171 centres and 102 family associations were received from 42 countries. The median proportion of time spent in paediatric practice in the centres examined was 100%, with 70% of this time dedicated to paediatric rheumatology. 90% of the centres were willing to perform clinical trials in the future. CONCLUSIONS: The PRINTO/PRES website provides a well defined and competent set of information about PRD, with appropriate multiple translated versions and easy web navigational direction.

Child↗
PubMed2003

Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study.

OBJECTIVE: To study infliximab and etanercept in the treatment of refractory juvenile idiopathic arthritis (JIA). METHODS: In a non-randomised, prospective, open label study, 24 patients (mean age 10.2 years, range 3.3-16.3) with polyarticular JIA were treated with either infliximab (n=14) or etanercept (n=10). The patients had had active polyarthritis for at least one year and standard treatment had failed. Anti-tumour necrosis factor (TNF) treatment was added to the current drug treatment. Infliximab (3-4 mg/kg) was given intravenously at weeks 0, 2, and 6, and thereafter at 4 to 8 week intervals. Etanercept (0.4 mg/kg) was given subcutaneously twice a week. Improvement of the patients was assessed at 3, 6, and 12 months according to established JIA response criteria. RESULTS: In intention to treat analyses, patients in both treatment groups improved significantly. ACR Paediatric 50 was achieved at 3, 6, and 12 months by 9/10 (90%), 8/9 (89%), and 8/9 (89%) patients with etanercept and by 8/12 (67%), 10/12 (83%), and 7/9 (78%) with infliximab, respectively. At 12 months, ACR Paediatric 75 was achieved by 67% of patients in both treatment groups. Five withdrawals due to adverse effects or lack of efficacy occurred in the infliximab group and one due to lack of compliance in the etanercept group. CONCLUSION: In this open label clinical study of active JIA, both infliximab and etanercept provided a significant rapid and sustained reduction in disease activity. Adequately powered randomised controlled trials are needed to elucidate the long term safety and efficacy of TNF modulators in the treatment of JIA.

Adolescent↗
PubMed2002

Campylobacter-triggered reactive arthritis: a population-based study.

OBJECTIVE: To study the incidence and clinical picture of Campylobacter-associated reactive arthritis (ReA) and other reactive musculoskeletal symptoms in the population. METHODS: A questionnaire on enteric and extraintestinal, including specifically musculoskeletal, symptoms was sent to 870 consecutive patients with Campylobacter-positive stool culture and 1440 matched controls. Analysis of self-reported musculoskeletal symptoms with clinical examination was performed. RESULTS: Forty-five of the patients (7%) had ReA and eight (1%) had reactive tendinitis, enthesopathy or bursitis. No child had ReA. The arthritis was oligo- or polyarticular, and, in most cases, mild. HLA-B27 was positive in 14% of ReA patients. Of the 45 ReA patients, 37 had C. jejuni and 8 had C. coli infection. No controls had ReA. CONCLUSION: ReA is common following Campylobacter infection, with an annual incidence of 4.3 per 100000. At the population level, acute ReA is mild, more frequent in adults, and not associated with HLA-B27. Besides C. jejuni, C. coli can trigger ReA.

Adult↗
PubMed2001

Recombinant flagellin A proteins from Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii in serodiagnosis of Lyme borreliosis.

Genes for flagellin A (FlaA) proteins from European borrelial strains of Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii were cloned and sequenced. An identity of 92 to 93% was observed in the flaA sequences of the different species. Polyhistidine-tagged recombinant FlaA (rFlaA) proteins were produced in Escherichia coli and used as antigens in Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). In immunoglobulin G (IgG) WB, 71% (10 of 14) of the sera from neuroborreliosis and 86% (12 of 14) of those from Lyme arthritis patients reacted with one to three rFlaAs. In IgG ELISA, 74% (14 of 19) and 79% (15 of 19) of patients with neuroborreliosis and arthritis, respectively, were positive. The immunoreactivity in local European patient sera was stronger against rFlaA from B. garinii and B. afzelii than against rFlaA from B. burgdorferi sensu stricto. Neither IgG nor IgM ELISA was sensitive in the serodiagnosis of erythema migrans. Serum samples from patients with syphilis and systemic lupus erythematosus showed mild cross-reactivity in IgG tests. Sera from Yersinia enterocolitica or beta-hemolytic Streptococcus infections showed only occasional responses. With IgM ELISA, 58% (11 of 19) and 37% (7 of 19) of patients with neuroborreliosis and arthritis, respectively, were positive. Cross-reactive antibodies to FlaA, especially in serum samples from patients with rheumatoid factor positivity and Epstein-Barr virus infection, reduced the specificity of IgM serodiagnosis. Therefore, rFlaA seems to have a limited role for IgM serodiagnosis, yet rFlaA might be useful in the IgG serodiagnosis of disseminated Lyme borreliosis.

Amino Acid Sequence↗
PubMed2001

Construct validity of ILAR and EULAR criteria in juvenile idiopathic arthritis: a population based incidence study from the Nordic countries. International League of Associations for Rheumatology. European League Against Rheumatism.

OBJECTIVE: New classification criteria (ILAR) have been proposed for juvenile idiopathic arthritis (JIA). They are more descriptive than those formerly used [American College of Rheumatology (ACR), European League Against Rheumatism (EULAR)], but require validation against classifications already in use. We validated the ILAR criteria in relation to the EULAR criteria in a prospective, incidence, and population based setting, and analyzed their feasibility. METHODS: Construct validity of ILAR and EULAR classification criteria refers to how closely the 2 instruments are related and how each of them operates in classifying subgroups/categories. Twenty doctors in 5 Nordic countries collected data from the incidence cases within their catchment areas during an 18 month period beginning July 1, 1997. Clinical and serological data from the first year of disease were collected. RESULTS: A total of 322 patients were included. Classification according to the ILAR criteria was possible in 321 patients; 290 patients had a disease duration > or = 3 months and were classified according to the EULAR criteria. One child could only be classified according to the EULAR criteria. Thus, 31/322 (9.6%) children were classified according to the ILAR criteria only. Forty-eight of 321 (15%) patients did not fit into any category and 6% (20/321) fulfilled criteria for2 categories. In the ILAR classification 5 out of 7 categories/subgroups have 2 to 5 specified exclusion criteria that highly discriminate the definition of each patient. In our study the exclusion criteria were fulfilled to only a small extent. CONCLUSION: The EULAR and ILAR criteria differ concerning the operational definitions of the subvariables involved, which complicates their comparison. By using ILAR rather than EULAR criteria the number of cases with juvenile arthritis increased by 10%, considering the first half-year after onset. The validity of the ILAR criteria is low since they often exclude patients from subgroup classification and the possibility of having more than one diagnosis is not negligible. The specified exclusion criteria for some of the subgroups are difficult to fulfill in clinical work and variables involved could be questioned with regard to their consistency.

Adolescent↗
PubMed2000

The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi.

Spirochete bacteria of the Borrelia burgdorferi sensu lato complex cause Lyme borreliosis. The three pathogenic subspecies Borrelia garinii, Borrelia afzelii, and Borrelia burgdorferi sensu stricto differ in their disease profiles and susceptibility to complement lysis. We investigated whether complement resistance of Borreliae could be due to acquisition of the main soluble inhibitors of the alternative complement pathway, factor H and the factor H-like protein 1. When exposed to nonimmune EDTA-plasma, the serum-resistant B. afzelii and B. burgdorferi sensu stricto strains bound factor H/factor H-like protein 1 to their surfaces. Assays with radiolabeled proteins showed that factor H bound strongly to the B. burgdorferi sensu stricto strain. To identify factor H ligands on the borrelial surface, we analyzed a panel of outer surface proteins of B. burgdorferi sensu stricto with the surface plasmon resonance technique. The outer surface lipoprotein OspE was identified as a specific ligand for factor H. Using recombinant constructs of factor H, the binding site for OspE was localized to the C-terminal short consensus repeat domains 15-20. Specific binding of factor H to B. burgdorferi sensu stricto OspE may help the pathogen to evade complement attack and phagocytosis.

Antigens, Bacterial↗
PubMed1998

Decorin-binding protein of Borrelia burgdorferi is encoded within a two-gene operon and is protective in the murine model of Lyme borreliosis.

Isolated outer membranes of Borrelia burgdorferi were used in immunoblotting experiments with sera from immune mice to identify new putative Lyme disease vaccine candidates. One immunoreactive polypeptide migrated on polyacrylamide gels just proximal to outer surface protein C and comigrated with [3H]palmitate-labeled polypeptides. A degenerate oligonucleotide primer based upon internal amino acid sequence information was used to detect the corresponding gene within a B. burgdorferi total genomic library. The relevant open reading frame (ORF) encoded a polypeptide comprised of a 24-amino-acid putative signal peptide terminated by LLISC, a probable consensus sequence for lipoprotein modification, and a mature protein of 163 amino acids. Immunoblots of a recombinant fusion protein corresponding to this ORF supported the idea that the encoded protein was a previously reported decorin-binding protein (DBP) of B. burgdorferi N40 (B. P. Guo, S. J. Norris, L. C. Rosenberg, and M. Höök, Infect. Immun. 63:3467-3472, 1995). However, further DNA sequencing revealed the presence of a second ORF, designated ORF-1, whose termination codon was 119 bp upstream of the dbp gene. ORF-1 also encoded a putative lipoprotein with a mature length of 167 amino acids. Northern blots, Southern blots, and primer extension analyses indicated that ORF-1 and dbp comprised a two-gene operon located on the 49-kb linear plasmid. Both proteins, which were 40% identical and 56% similar, partitioned into Triton X-114 detergent extracts of B. burgdorferi isolated outer membranes. Mice infected with B. burgdorferi produced high titers of antibodies against the ORF-1-encoded protein and DBP during both early and later stages of chronic infection. Both DBP and the ORF-1-encoded protein were sensitive to proteinase K treatment of intact borreliae, suggesting that they were surface exposed. In active immunization experiments, 78% of mice immunized with recombinant DBP were immune to challenge. While it is not clear whether the two lipoproteins encoded by the ORF-1-dbp operon have analogous decorin-binding functions in vivo, the combined studies implicate DBP as a new candidate for a human Lyme disease vaccine.

Adhesins, Bacterial↗
PubMed1997

Molecular characterization of a 6.6-kilodalton Borrelia burgdorferi outer membrane-associated lipoprotein (lp6.6) which appears to be downregulated during mammalian infection.

Isolated outer membranes of Borrelia burgdorferi 297 were utilized to obtain partial amino acid sequence information for a low-molecular-weight, outer membrane-associated polypeptide. Degenerate oligonucleotide primers based upon this information were used to amplify a 100-bp probe for detection of the corresponding full-length gene within a B. burgdorferi total genomic library. The relevant open reading frame (ORF) encoded a polypeptide comprised of a 17-amino-acid putative signal peptide terminated by LFVAC, a probable consensus sequence for lipoprotein modification, and a mature protein of 51 amino acids (predicted molecular mass of 5.8 kDa). The DNA sequences of the corresponding ORFs in B. burgdorferi 297 and B31 were identical; the corresponding ORF in strain N40 differed by only one nucleotide. Assuming conventional processing and acylation, the molecular weight of the lipoprotein, designated lp6.6, is about 6,600. The lp6.6 gene, which was localized to the 49-kb linear plasmid of B. burgdorferi, subsequently was cloned and expressed in Escherichia coli as a fusion protein with glutathione S-transferase. Immunoblot analysis with monoclonal antibody 240.7 revealed that lp6.6 was identical to a low-molecular-weight, highly conserved B. burgdorferi lipoprotein reported previously (L. I. Katona, G. Beck, and G. S. Habicht, Infect. Immun. 60:4995-5003, 1992). Results of indirect immunofluorescence assays, growth inhibition assays, passive immunizations, and active immunizations indicated that this outer membrane-associated antigen is not surface exposed in B. burgdorferi. Particularly interesting was the finding that mice and rhesus monkeys chronically infected with B. burgdorferi failed to develop antibodies against this antigen. We propose that high-level expression of lp6.6 is associated with the arthropod phase of the spirochetal life cycle and that expression of the gene is downregulated during mammalian infection.

Amino Acid Sequence↗
PubMed1996

Limited surface exposure of Borrelia burgdorferi outer surface lipoproteins.

We used novel immunofluorescence strategies to demonstrate that outer surface proteins (Osps) A, B and C of Borrelia burgdorferi have limited surface exposure, finding that contradicts the prevailing viewpoint that these antigens are exclusively surface exposed. Light labeling was observed when antibodies to OspA or OspB were added to motile organisms, whereas intense fluorescence was observed when the same slides were methanol-fixed and reprobed. Modest labeling also was observed when spirochetes encapsulated in agarose beads (gel microdroplets) were incubated with antibodies to these same two antigens. This contrasted with the intense fluorescence observed when encapsulated spirochetes were probed in the presence of 0.06% Triton X-100, which selectively removed outer membranes. Proteinase K (PK) treatment of encapsulated spirochetes abrogated surface labeling. However, PK-treated spirochetes fluoresced intensely after incubation with antibodies to OspA or OspB in the presence of detergent, confirming the existence of large amounts of subsurface Osp antigens. Modest surface labeling once again was detected when PK-treated spirochetes were reprobed after overnight incubation, a result consistent with the existence of a postulated secretory apparatus that shuttles lipoproteins to the borrelial surface. Last, experiments with the OspC-expressing B. burgdorferi strain 297 revealed that this antigen was barely detectable on spirochetal surfaces even though it was a major constituent of isolated outer mem- branes. We propose a model of B. burgdorferi molecular architecture that helps to explain spirochetal persistence during chronic Lyme disease.

Animals↗
PubMed1995

Tumor markers CA 125 and CA 19-9 in cord blood and during infancy: developmental changes and use in pediatric germ cell tumors.

Tumor markers CA 125 and CA 19-9 are elevated in a variety of malignancies in adult patients, but only little is known of their biology during gestation or infancy. We have addressed the developmental pattern of these carbohydrate antigens in pediatric patients by measuring their serum levels in 133 cord blood samples from the second through third trimester of gestation and in 39 infants aged less than 1.5 y. The serum concentrations of both markers revealed developmental changes, the levels being higher at earlier gestation (wk 24 through 37) than at term or during infancy. The clinical value of the markers was evaluated by monitoring 26 children with germ cell tumors; 14 benign and 2 immature teratomas, and 11 malignant germ cell tumors. Patients with immature sacrococcygeal teratomas showed constant and prolonged elevations of serum CA 125 and CA 19-9. In contrast, all but two children with mature teratomas had normal marker levels; these two patients with abnormally high serum CA 125 and CA 19-9 values for the first 4 postoperative weeks had a benign ovarian and ventricular teratoma, respectively. Of the 11 children with malignant germ cell tumors, serum CA 125 or CA 19-9 concentration was elevated in four patients at diagnosis and declined to normal within 2 wk after institution of therapy. Malignant recurrence in two patients was not associated with a reelevation of the CA 125 level. Taken together, our results demonstrate a developmentally regulated pattern of serum CA 125 and CA 19-9. The carbohydrate markers were usually inferior to alpha-fetoprotein in monitoring of germ cell tumors, but may be a useful adjunct in the follow-up of immature teratomas.

CA-125 Antigen↗
PubMed1993

Neonatal benign sacrococcygeal teratoma may recur in adulthood and give rise to malignancy.

BACKGROUND: The capacity of neonatal sacrococcygeal teratomas (SCT) to recur is a well-recognized phenomenon. However, only a few studies have reported recurrence of the tumors beyond childhood. METHODS: A follow-up of patients for the detection of late recurrent SCT was performed in 45 patients, ages 4-43 years (mean, 21.5 years). All of the patients had been operated on in infancy for a benign SCT. RESULTS: Three adults with persistent or recurrent SCT were found. The recurrent tumors were diagnosed 21-43 years after the initial diagnosis and operative treatment. Two recurrences were histologically benign, and one was malignant. In the patient with the malignant recurrence, the coccyx was not removed primarily. The malignant recurrence was a mucinous adenocarcinoma and probably originated from a preexisting benign epithelial component of the teratoma. CONCLUSIONS: The capacity of a benign SCT to recur may be retained into adulthood. Follow-up of patients after operation for a SCT, even when the tumor is benign, should extend far beyond infancy. Abdominal radiographs may help detect late recurrent tumors with intrapelvic calcifications. When any recurrence is found, malignancy should be suspected.

Adenocarcinoma, Mucinous↗
PubMed1993

Anorectal function in adults operated for a benign sacrococcygeal teratoma.

Fecal continence and quality of life were evaluated by a questionnaire in 26 adult patients (mean age, 30 years; 6 men, 20 women) who had undergone surgery for a benign sacrococcygeal teratoma in infancy. The fecal continence was assessed by a score described by Holschneider. Twenty-six healthy people with a similar age and sex distribution were used as controls. Good fecal continence was reported by 88% of the patients; however, only 27% had completely normal bowel habits. Some fecal soiling was present in 27% of the patients. No correlation between the severity of aberrations in anorectal functions and the degree of intrapelvic extension of the tumor was found. Social problems related to deficient anorectal function were reported by 27% of the patients. Other health problems including urinary incontinence were reported by 50% of the patients. All the controls had good fecal continence; 77% of them had completely normal bowel habits. The present study shows that at the adult age, a significant proportion of patients who have undergone surgery for sacrococcygeal teratoma suffer from deficient anorectal function and a diminished quality of life.

Adult↗
PubMed1992

Late sequelae of gonadal, mediastinal and oral teratomas in childhood.

Thirty-two patients with gonadal or non-sacrococcygeal extragonadal teratomas who underwent operation in childhood were evaluated for different late sequelae. Follow-up times ranged from 5.0 to 40 years. Physical abnormalities resulting from surgery were seen in eight patients who had had oral or mediastinal primary teratomas. Radiographs revealed multiple spina bifida occulta lesions in three patients. The males, but not the females, showed signs of gonadal dysfunction. Impaired semen quality or abnormal serum concentrations of testosterone or gonadotrophins were found in five of 10 adult men who had had testicular or mediastinal teratomas. Thus, some late sequelae may be predicted from the site of the primary teratoma, but gonadal dysfunction in males and vertebral anomalies may occur irrespective of where the teratoma is situated.

Adolescent↗
PubMed1991

Biphasic reduction and concanavalin A binding properties of serum alpha-fetoprotein in preterm and term infants.

Reference values for postnatal serum alpha-fetoprotein (AFP) and concanavalin A (ConA) binding subfractions of AFP in preterm and term infants are presented. Preterm infants had 10-fold higher serum concentrations of AFP than did term infants at birth. The reduction of serum values of AFP was biphasic in both groups and differed significantly between the two groups. The first declining phase continued for approximately 4 months in preterm and for 2 months in term infants, and was related to the degree of prematurity. The AFP values reached adult levels by 12 months in preterm and by 9 months in term infants. The developmental pattern of the carbohydrate moiety of AFP was determined by ConA fractioning. The proportion of the ConA nonreactive subfraction of AFP in preterm and term infants at birth was 6% and 13%, respectively; it increased more rapidly in term than in preterm infants but reached 85% to 95% by the age of 6 months in both infant groups. Our results indicate that the postnatal maturation of AFP synthesis is dependent on gestational age. Malignant recurrences of neonatal sacrococcygeal teratomas were associated with an increase in serum concentration of AFP and a decrease in the proportion of the ConA nonreactive subfraction of AFP.

Concanavalin A↗
PubMed1990

Cell differentiation in sacrococcygeal teratomas. An immunohistochemical and follow-up study.

The cell differentiation properties of thirty-four sacrococcygeal teratomas (SCT) and their five recurrences were immunohistochemically studied for the expression of different classes of intermediate filament proteins, muscle actin (MA) and S-100 protein. Out of thirty-nine tumors twenty-three were SCTs with only mature tissue elements, seven immature teratomas, five pure endodermal sinus tumors (EST) and four ESTs or embryonal carcinomas (EC) combined with mature components. Cytokeratin positivity was found in all epithelial structures and sometimes also in smooth muscle and primitive mesenchymal cells. An intense cytokeratin immunoreactivity was observed in EC and EST components. Muscle markers, desmin and MA were present in smooth and striated muscle cells. Focal desmin positivity was also found in some epithelial structures in two cases. Glial tissue positive for glial fibrillary acidic protein (GFAP) was found in twenty-eight out of thirty-nine tumors. Some cases with no apparent glial tissue in hematoxylin and eosin staining showed glial differentiation as proved by GFAP positivity. In six out of eleven choroid plexus-like tissues GFAP positive cells were observed. S-100 protein showed an intense distribution of immunoreactivity outside neural tissue, and focal positivity was observed in malignant epithelial structures. Immunohistochemical markers did not reveal any prognostic significance in teratomas. Our findings, however, showed some aberrant features of cell differentiation from normal mature tissue components but closely parallel to those found in normal fetal development.

Actins↗