Biomedical subjects

J Partanen

Publications and source records attributed to J Partanen.

At least 19 recordsLinked to original sources

PubMed2007

T cell regeneration in pediatric allogeneic stem cell transplantation.

Delayed and/or insufficient T cell recovery post hematopoietic stem cell transplantation (HSCT) leads to an increased risk of morbidity and mortality. We evaluated thymic function and its association with T cell regeneration post HSCT and identified factors involved in the process among pediatric stem cell transplant recipients. T cell regeneration in 66 pediatric patients was prospectively followed by naive T cell phenotyping, measuring of T cell receptor excision circles (TRECs) and expression of Foxp3 by regulatory T cells for the first 18 months post HSCT. TRECs were lower pre-HSCT in children with a malignant than non-malignant primary disease or immunosuppressed controls (P=0.001). Naive T lymphocyte reconstitution and thymic recovery were slow in the recipients of allogeneic stem cell grafts post HSCT. Infections caused by herpesviruses had a prognostic impact on mortality. Children with low TRECs had a high mortality (P=0.05) and low TRECs were also associated with extensive chronic graft-versus-host disease from 6 months onwards. Low amount of Foxp3 pre-HSCT was associated with an increased mortality post HSCT (P=0.03). Our study indicates an association between impaired T cell regeneration and thymic dysfunction and the clinical post transplant complications in pediatric allogeneic stem cell transplantation.

Adolescent↗

PubMed2006

Diagnostic significance of HLA-DQ typing in patients with previous coeliac disease diagnosis based on histology alone.

BACKGROUND: Coeliac disease is strongly associated with human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes. The diagnosis is based on demonstrating crypt-hyperplastic villous atrophy, endomysial or transglutaminase antibodies and correlation of disease activity with gluten intake. AIM: To evaluate the clinical utility of HLA-DQ typing, when coeliac disease diagnosis had previously been established solely by histology. METHODS: HLA-DQ alleles, endomysial and transglutaminase antibodies were investigated and histology slides reviewed in 70 patients diagnosed 2-25 years earlier by small-intestinal biopsy but without measuring endomysial or transglutaminase antibodies. Patients without DQ2 or DQ8 or without unequivocal villous atrophy were followed-up on free diet by using serology and biopsies. RESULTS: All 40 endomysial/transglutaminase antibodies positive patients carried DQ2 or DQ8, and 39 of them had severe villous atrophy. Only 56% of patients without endomysial or transglutaminase antibodies positivity had DQ2 or DQ8 (P < 0.001). Seropositivity and relapse developed in 4 of 11 DQ2 positive but in none of 15 DQ2 and DQ8 negative patients on long-term gluten exposure. CONCLUSIONS: Coeliac disease diagnosis based solely on histology is not always reliable. HLA-DQ typing is important in identifying DQ2 and DQ8 negative subjects who need revision of their diagnosis, but it does not have additive diagnostic value if endomysial positivity is already known.

Adolescent↗

PubMed2006

Immunoglobulin A autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming coeliac disease.

BACKGROUND: Reliable markers of early developing coeliac diseases are needed. Coeliac autoantibodies in the serum or Marsh I inflammation may be indicators of subsequent coeliac disease. AIM: To investigate whether determination of intestinal transglutaminase 2-targeted autoantibody deposits would detect early developing coeliac disease better than previous methods. METHODS: The study investigated patients previously excluded for coeliac disease: 25 had positive serum coeliac autoantibodies (endomysial), 25 antibody-negative had Marsh I, and 25 antibody-negative had Marsh 0 finding. Seven (median) years after baseline investigation, new coeliac cases were recorded, and small bowel biopsy was offered to the rest of the patients. Serum and intestinal coeliac autoantibodies and intraepithelial lymphocytes were assessed as indicators of developing coeliac disease. RESULTS: Seventeen patients had developed coeliac disease: 13 in the autoantibody-positive group, three in the Marsh I group and one in the Marsh 0 group. At baseline, intestinal coeliac autoantibody deposits had a sensitivity and specificity of 93% and 93% in detecting subsequent coeliac disease, CD3+ 59% and 57%, gammadelta+ 76% and 60%, and villous tip intraepithelial lymphocytes 88% and 71%, respectively. CONCLUSIONS: Endomysial antibodies with normal histology indicates early developing coeliac disease. Transglutaminase 2-targeted intestinal autoantibody deposits proved the best predictor of subsequent coeliac disease.

Adolescent↗

PubMed2006

Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits.

BACKGROUND: Some patients with untreated coeliac disease are negative for serum endomysial autoantibodies (EmA) targeted against transglutaminase 2 (TG2). AIMS: To evaluate the clinical and histological features of EmA-negative coeliac disease, and to examine whether EmA-equivalent autoantibodies against TG2 can be seen in the small-bowel mucosa when absent in serum. PATIENTS: Serum EmA was studied in 177 biopsy-proved specimens from adult patients with coeliac disease. 20 patients with intestinal diseases served as non-coeliac controls; three had autoimmune enteropathy with villous atrophy. METHODS: Clinical manifestations, small-bowel mucosal morphology, intraepithelial inflammation and TG2-specific extracellular immunoglobulin A (IgA) deposits were investigated in both serum EmA-negative and EmA-positive patients. RESULTS: 22 patients with IgA-competent coeliac disease were negative for serum EmA. Three of these had small-bowel lymphoma. Patients with EmA-negative coeliac disease were older, had abdominal symptoms more often, and the density of gammadelta+ intraepithelial lymphocytes in their intestinal mucosa was lower than in EmA-positive patients; otherwise the histology was similar. All serum EmA-negative patients with coeliac disease, but none of the disease controls, had gluten-dependent mucosal IgA deposits alongside TG2 in the small-bowel mucosal specimens. In vivo deposited IgA was shown to be TG2-specific by its ability to bind recombinant TG2. CONCLUSIONS: Negative serum EmA might be associated with advanced coeliac disease. TG2-targeted autoantibodies were deposited in the small-bowel mucosa even when absent in serum. This finding can be used in the diagnosis of seronegative coeliac disease when the histology is equivocal. It may also be helpful in the differential diagnosis between autoimmune enteropathy and coeliac disease.

Adolescent↗

PubMed2006

HLA-DRB1, -DQB1 alleles in head and neck carcinoma patients.

Certain HLA class II alleles have been reported to play a role in development or prevention of cervical carcinoma, an epithelial malignancy linked to human papillomavirus (HPV). In head and neck carcinomas, of which a subset is also HPV associated, the impact of HLA genes remains unknown. HLA-DRB1, -DQB1 alleles were determined in a comprehensive series of 162 head and neck carcinoma patients, for which 83 consecutive cadaveric organ donors of Finnish origin served as controls. DRB1*03 was associated with node-negative disease and DRB1*08 and 13 with small tumors; DRB1*04 was protective against disease relapse. Most alleles of borderline significance in this study act similarly in cervical carcinomas.

Alleles↗

PubMed2006

Hip fracture treatment in Oulu--one-year survey with four-month follow-up.

BACKGROUNDS AND AIMS: The standardized forms of the Standardized Audit of Hip Fractures in Europe (SAHFE) are aimed for the evaluation of hip fracture treatment in different hospitals and countries. The purpose was to evaluate and characterize a cohort of hip fracture patients with these forms and to evaluate their value in quality control. MATERIAL AND METHODS: The non-pathological hip fractures in patients over 49 years of age treated in the Oulu University Hospital were prospectively recorded during a one-year period using SAHFE forms. RESULTS: There were 238 (52 male and 186 female) patients with a mean age of 78 (50-102) years. Fifty-nine percent of the patients were admitted from their own homes. Fifty-seven percent were able to walk alone outdoors and 48% could walk without walking aids before the fracture. A hundred and fifty patients had cervical fractures and 88 trochanteric fractures. The most frequent treatment of cervical fractures was Austin-Moore hemiarthroplasty (68%) and that of trochanteric fractures Gamma nail fixation (86%). At four months after the fracture, 50% lived in their own homes, 33% could walk alone outdoors and 13% could walk without any aids. Thirty-two percent had no pain in the hip. The overall mortality at four months was 17.6% and that of the operated patients 16.2%. The reoperation rate was 8.5%. CONCLUSION: SAHFE forms were very useful in the evaluation of the quality of the hip fracture treatment.

Activities of Daily Living↗

PubMed2005

Impact of deep infection after hip fracture surgery on function and mortality.

Our aim was to evaluate the impact of deep wound infection after hip fracture surgery on functional outcome and mortality. Two thousand, two hundred and seventy-six consecutive surgically treated patients with non-pathological fractures, aged over 50 years (mean age 78.3 years), were followed up prospectively. The 29 patients who had deep infection (rate 1.3%) and who received revision surgery were compared with controls without infection, matched for age, sex, residential status at fracture, fracture type, treatment method and walking ability. When the functionality of hip fracture patients was evaluated four months after the primary operation, the patients with deep wound infection had impaired walking ability (P=0.039) and required walking aids, including wheelchairs, more often than the control patients (48% vs 20.8%, P=0.022). At four months, the mean duration of hospitalization at the primary hospital was significantly longer for the cases than the controls (P<0.001). Diabetes was more common in the patients with deep infection (P=0.038). Staphylococcus aureus was the most commonly isolated micro-organism, and it was associated with higher one-year mortality (57%) than the other bacteria (14.3%, P=0.014); the overall mortality of the infected patients and controls was 34.5% and 24.1% at one year, respectively (P=0.508). In conclusion, deep infection after a hip fracture operation impairs short-term functional outcome and slightly increases mortality, with an excess mortality rate of 10.4%.

Aged↗

PubMed2005

Recovery of N100 component of auditory event-related potentials and EEG after cardiac arrest during propofol sedation.

We report on the EEG monitoring of a patient who suffered an episode of postoperative ventricular fibrillation (VF) following coronary artery bypass grafting (CABG). VF initially caused a considerable suppression and slowing of the EEG. The recovery of cerebral function was evaluated by recording both EEG and auditory event related potentials (ERPs). Six hours after the episode of VF, when the patient was asleep but arousable to voice command, the N100 component of the auditory ERPs had recovered to the level measured before the operation, whereas the EEG was still very slow for that level of sedation. This may have been due to VF having less effect on the N100 component than on the background EEG. Our findings suggest that measuring evoked potentials may improve the evaluation of brain function after cardiac arrest.

Aged↗

PubMed2005

Collection of autologous blood for bone marrow donation: how useful is it?

The hospital charts of 495 adult bone marrow (BM) donors to adult patients were reviewed to determine how necessary it is to collect autologous blood for marrow donation. An autologous transfusion was given to 79% of the donors. The median total volume of marrow harvested was 900 ml (range 450-1350 ml). The median number of nucleated cells harvested was 3.2 x 10(8)/kg patient weight (range 0.9-7.4 x 10(8)/kg patient weight). On the morning following the harvest, the median haemoglobin (Hb) concentrations were 104 g/l (79-135 g/l) in the female and 122 g/l (89-151 g/l) in the male donors autotransfused, and 96 g/l (75-127 g/l) in the female and 119 g/l (88-141 g/l) in the male donors not autotransfused. The post-donation Hb was lower than 85 g/l in four and lower than 90 g/l in 25 donors. Of the 25 donors with post-harvest Hb lower than 90 g/l, 23 were females and 14 had received an autologous transfusion. This study shows that, with a few exceptions, it is not necessary to collect autologous blood from healthy BM donors before the marrow harvest. The post-donation Hb concentrations do not decrease to levels detrimental to healthy persons whether autologous blood is transfused or not.

Adolescent↗

PubMed2005

Cytokine gene polymorphisms and genetic association with coeliac disease in the Finnish population.

Coeliac disease (CD) is an intestinal disorder caused by intolerance to dietary gluten in susceptible individuals. The HLA-DQ genes are major risk factors for CD, but other genes also play an important role in the disease susceptibility. Immune-mediated mechanisms are known to underlie the pathogenesis of CD. We studied single-nucleotide polymorphisms in transforming growth factor (TGF)-beta1, interleukin (IL)-10, IL-6, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha genes in the Finnish population using family-based association approach. In addition, we genotyped a trinucleotide repeat polymorphism in the major histocompatibility complex (MHC) class I chain-related protein A (MICA) gene, located in the human leucocyte antigen (HLA) region in the vicinity of TNF-alpha. To control the effect of linkage disequilibrium between HLA-DQ genes and MICA and TNF-alpha, an HLA-stratified association analysis was performed. We did not find evidence of association between TGF-beta1, IL-10, IL-6 and IFN-gamma polymorphisms and CD susceptibility. No association was found for any of the MICA alleles independently of DQ genes, whereas TNF-alpha-308 A allele was slightly overrepresented on chromosomes carried by CD patients compared with control chromosomes, indicating that either TNF-alpha, or another gene in linkage disequilibrium with it, could confer increased susceptibility to CD. This result supports the earlier findings that the HLA region harbours a novel susceptibility factor in addition to HLA-DQ.

Alleles↗

PubMed2005

The DR4-DQ8 haplotype and a specific T cell receptor Vbeta T cell subset are associated with absence of allergy to Can f 1.

BACKGROUND: The significance of specific T cell receptor (TCR) Vbeta subtypes and human leucocyte antigen (HLA) class II alleles for the development of allergy to lipocalin allergens such as the major dog allergen Can f 1 is not clear at present. OBJECTIVE: To characterize the TCR Vbeta usage in the Can f 1-specific T cell lines and the HLA class II genotypes of Can f 1-allergic and non-allergic subjects. METHODS: T cell lines were induced with recombinant Can f 1 from the peripheral blood mononuclear cells of 12 non-atopic dog owners and 26 dog-allergic patients. Thirteen of the dog-allergic subjects were sensitized to Can f 1. Expression of the TCR Vbeta subtypes on CD4(+) T cells in the T cell lines was measured by flow cytometry. The subjects were HLA genotyped for DRB1, DQB1 and DPB1 loci. RESULTS: Can f 1-specific T cell lines were obtained from 18 subjects, with either positive (n=8) or negative (n=10) skin prick tests (SPTs) to recombinant Can f 1. The frequency of TCR Vbeta5.1(+) T cells was significantly higher in the T cell lines of subjects with negative SPTs to the allergen. Moreover, DR4-DQ8 haplotype was over-represented among these subjects. CONCLUSION: The DR4-DQ8 haplotype and the TCR Vbeta5.1(+) CD4(+) T cells may be protective against allergy to Can f 1.

Allergens↗

PubMed2005

Genetic diversity of KIR natural killer cell markers in populations from France, Guadeloupe, Finland, Senegal and Réunion.

Killer cell immunoglobulin-like receptors (KIRs) belong to a diverse family of natural killer (NK) cell receptors recognizing human leukocyte antigen (HLA) class I molecules. Due to this functional link, KIR molecules are expected to display a high polymorphism, such as their HLA ligands. Moreover, many studies conducted in mouse and human models have shown that NK-KIR receptors play an important role in haematopoietic stem cell transplantation (HSCT). A beneficial impact of peculiar KIR ligand (HLA) mismatching has been reported suggesting a role to this combinatory HLA-KIR polymorphism. It is thus important to investigate KIR diversity in various human populations. To this end, we used polymerase chain reaction-sequence-specific primers to evaluate KIR gene in five selected populations (France, Guadeloupe, Senegal, Finland and Réunion). Genotypic and haplotypic frequencies were computed, as well as genetic distances and dendrogram (phylip package). These data illustrate the genetic relationship of these five populations through the KIR polymorphism. Results revealed a wide diversity in KIR gene frequencies in Guadeloupe and Réunion, and a high specificity in Senegal. The obtained dendrogram indicated small genetic distances between France, Guadeloupe and Réunion as well as between France and Finland. Senegal showed a distant genetic relationship with the other countries and, interestingly, an inverted ratio of coding/non-coding (KIR2DS4/1D) alleles compared with Caucasians. These data expose the broad diversity in KIR genes worldwide and show that KIR genes are pertinent tools in human population genetics. If the role of KIR donor-recipient incompatibilities is confirmed, KIR diversity according to ethnicity should be taken into account during the selection of HSCT donors.

Alleles↗

PubMed2004

Preoperative clinical evaluation, outline of surgical technique and outcome in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most common type of refractory epilepsy. The mechanisms of epileptogenesis and seizure semiology of the mesial and neocortical temporal lobe epilepsy are discussed. The evaluation and selection of patients for TLE surgery requires team work: the different clinical aspects of neuropsychological evaluation, magnetic resonance and functional imaging (positron emission tomography, single photon emission computed tomography and magnetoenephalography) are reviewed. In our programme of epilepsy surgery at Kuopio University Hospital, Finland, we have performed 230 temporal resections from 1988 until 2002. Preoperative diagnostic EEG-videotelemetry often required intracranial monitoring and it has proved to be safe and efficient. The indications and technique for tailored temporal lobe resection with amygdalohippocampectomy used in our institution, as well as the complications, are described. Our analysis of outcome after temporal lobe surgery included 140 consecutive adult patients between 1988 and 1999; one year after the operation in unilateral TLE the Engel I-II outcome was observed in 68% of the patients. Outcome of surgery improved significantly after introduction of the standardised MR imaging protocol from 1993; 74% of patients with unilateral TLE achieved Engel I-II outcome.

Electroencephalography↗

PubMed2004

Genetic association of coeliac disease susceptibility to polymorphisms in the ICOS gene on chromosome 2q33.

An interesting candidate gene region for coeliac disease (CD), a common multifactorial disease, is a segment on 2q33-37 harbouring the genes for the CD28, cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), inducible costimulator (ICOS), and programmed death-1 (PD-1), all receptors that regulate lymphocyte activation. Several studies have suggested a role for this locus in immune-mediated diseases. To study further our previous finding of genetic linkage of this region to CD, we studied 25 polymorphic markers to identify the putative disease-associated polymorphism. Transmission/disequilibrium test in 106 Finnish families with CD indicated that only four polymorphisms, all located in the ICOS gene, showed evidence for genetic association. Strong linkage disequilibrium (LD), based on the analysis of 424 haplotypes, encompassed not only the associated ICOS markers but also many polymorphisms in the CTLA4 gene. Our results demonstrate that due to LD, it appears not easy to identify the genuine susceptibility factor in this region without larger multipopulation studies. Furthermore, the results did not support the evidence that polymorphisms in CTLA4 were the major susceptibility locus for CD.

Antigens, CD↗

PubMed2004

Villous tip intraepithelial lymphocytes as markers of early-stage coeliac disease.

BACKGROUND: An investigation was conducted to determine whether the density of small-intestinal villous tip intraepithelial lymphocytes would be of value in clinical practice in uncovering early-stage coeliac disease. METHODS: Villous tip, CD3+ and gammadelta+ intraepithelial lymphocytes were counted in patients with definite early-stage coeliac disease without villous atrophy, in classic coeliac disease with manifest mucosal lesion and in non-coeliac controls with normal mucosal structure. Villous tip analysis was made of haematoxylin-eosin specimens and CD3+ and gammadelta+ of immunohistochemical stainings from frozen samples. RESULTS: The villous tip intraepithelial lymphocyte count was statistically significantly higher in patients with early-stage coeliac disease than in non-coeliac controls. The sensitivity of this method to detect untreated coeliac disease with normal villous architecture was 0.84; the specificity was 0.88. This method proved superior to CD3+ analysis and was at least as good as gammadelta+ analysis in detecting early-stage coeliac disease. In detecting classic coeliac disease, villous tip analysis also reached a higher sensitivity than CD3+ and gammadelta+ cells. CONCLUSIONS: Villous tip analysis seems to distinguish early coeliac from non-specific changes, thus providing a valuable tool in routine practice, especially when borderline findings are involved. Its value appears to be similar to counting of gammadelta+ cells, which, however, requires frozen biopsy samples.

Adolescent↗

PubMed2004

Characterization a novel HLA-B40 allele with serological Bw4 motif, HLA-B4047, in the Finnish population and confirmation of B270503 allele.

We describe a novel HLA-B*40 allele assigned as B*4047*. The B*4047 allele was detected in a Finnish patient awaiting kidney transplantation. The patient had a "short" B60-like serological specificity with Bw4 association. After sequencing, the B*4047 allele was found to be identical to B*4001, except having five amino acid changes in exon 2, including the entire motif corresponding to Bw4 and w6 specificity. As a result of recombination or gene conversion, B*4047 has the Bw4 motif instead of expected Bw6. Screening of B40 alleles in the Finnish population revealed no other cases with this pattern, suggesting that this allele is rare. The sequence of B*270503 presented here provides the complete sequence for exons 2 and 3 for this allele. B*270503 allele differs from B*270502 by a single synonymous nucleotide substitution at non-variable position 489 in exon 3.

Base Sequence↗

PubMed2004

High birth weight is associated with human leukocyte antigen (HLA) DRB1*13 in full-term infants.

In cord blood banking, substantial amounts of data on infants and cord blood are gathered at high cost, including birth weights and human leukocyte antigen (HLA) genotypes. As certain HLA alleles have been associated with protective host responses, it is possible that an HLA allele, or another factor linked to it, might even affect normal intrauterine growth. We explored cord blood bank data (n = 1381 infants) to elucidate whether there is an association between birth weight and HLA class II (DRB1) alleles. HLA DRB1 data were available from 1263 infants. We observed an association between birth weight and HLA DRB1*13, which was over-represented among full-term infants with the highest birth weights. The association remained when the birth weight was corrected for varying gestational age (relative birth weight) according to gender (P = 0.015). After correction of the P-value for multiple comparisons, the association was not statistically significant. However, when the birth weights of all infants were analysed for the effect of DRB1*13, infants positive for HLA DRB1*13 (n = 319) were found to have higher birth weights than infants negative for this allele (n = 944; median 3690 g vs. 3650 g, respectively; P = 0.044). Although the difference in median birth weight was only 40 g, it may be considered significant because it appeared after segregation of the infants into two groups according to the single HLA class II allele group earlier associated with protection against, for example, childhood type 1 diabetes and certain infectious diseases. The present finding may thus suggest identification of a new factor affecting normal intrauterine growth.

Alleles↗

PubMed2004

Candidate gene region 2q33 in European families with coeliac disease.

Chromosome region 2q33 harbours a cluster of genes, CTLA-4, CD28, ICOS and closely located PD-1, all related to immune activation and considered as promising candidate genes for susceptibility to coeliac disease (CD). We present here the results of a genetic linkage and association analysis of nine markers located in this gene region in a large combined European material of 796 families with CD from Finland, Sweden, Norway, UK, France and Italy. The joint analysis supports earlier findings that this susceptibility locus, assigned as CELIAC3, merits further studies. Nominally significant linkage to CD was found in 314 families including affected sib pairs. Each of the five populations showed weak associations to several marker alleles, but the analysis revealed, however, no conclusive evidence for a primary functional gene or gene variant present in the total set of families. The results suggest that the CD risk due to 2q33 gene region is complex and may involve more than one susceptibility allele, which possibly differ from other autoimmune diseases.

Alleles↗