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J Partanen

Publications and source records attributed to J Partanen.

At least 37 records · Page 2Linked to original sources
PubMed2003

Additional factor in some HLA DR3/DQ2 haplotypes confers a fourfold increased genetic risk of celiac disease.

Although HLA-DQ genes are the major celiac disease (CD) susceptibility genes, results from Finnish families suggest that not all DQ2-encoding haplotypes confer equal susceptibility to CD, implying the effect of other gene(s) in the HLA region. The aim of the present work was to extend and confirm the aforementioned results in a southern European population ( Italian) and to better localize the additional risk factor/s. The association of nine loci spanning the HLA region from DR to HFE, 4.5-Mb telomeric of HLA-A, was tested. The analysis was performed by comparing marker frequencies in DR3-DQ2 haplotypes transmitted and non-transmitted to the affected offspring in 156 Italian CD families selected for having at least one DR3-positive parent. The same analysis was performed independently in 101 Finnish CD families selected with the same criteria. Three alleles, MICA-A5.1, MICB-CA24 and MIB-350, all characteristic of the B8-DR3 extended haplotype, showed a significantly increased frequency in DR3 transmitted haplotypes in the Italian families. DR3 haplotypes carrying the combination of these alleles conferred an approximate fourfold increased CD risk. B8-DR3 transmitted haplotypes were significantly more conserved telomerically down to the MIC-Class I region. Similar results were seen in the Finnish families. The major conclusion that holds true in both populations is that, while DQ2 is an absolute requirement for the development of CD, the presence of an additional genetic factor within the MIC-Class I region confers an approximate 4-fold increased risk of the disease.

Celiac Disease↗
PubMed2003

Single-trial estimation of multichannel evoked-potential measurements.

A method for single-trial estimation of multichannel evoked potentials is presented. The proposed method is based on the regularized least squares scheme. The spatial correlation between the channels is used as additional information in the estimation procedure. Amplitude estimates obtained with the proposed method is compared with the estimates calculated without using the spatial information. The performance of the method is evaluated using simulated and real data of P300 responses measured using auditory stimuli. The multichannel approach is shown to give realistic and comparable information about the amplitude differences of the P300 peak between different channels.

Action Potentials↗
PubMed2003

Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency.

BACKGROUND: IgA serum autoantibodies against tissue transglutaminase (tTG) have an established diagnostic value in coeliac disease, and high efficacy tests are widely available for their detection. However, serological evaluation of IgA deficient subjects is still difficult. AIMS: To evaluate the diagnostic potential of IgG class anti-tTG autoantibodies measured quantitatively using an enzyme linked immunosorbent assay (ELISA) compared with immunofluorescent detection of coeliac autoantibodies. PATIENTS: We tested serum samples from 325 IgA deficient subjects, including 78 patients with coeliac disease, 73 disease controls, and 174 blood donors. METHODS: IgG antibodies against human recombinant tTG were measured with an ELISA. IgG antiendomysium antibodies (EMA) were assayed by indirect immunofluorescence on human jejunum and appendix sections. RESULTS: The IgG anti-tTG ELISA had a sensitivity of 98.7% and a specificity of 98.6%, and the correlation with IgG EMA titres was high (r(s)=0.91). One coeliac patient, initially negative in all autoantibody tests, displayed both IgG anti-tTG antibodies and IgG EMA during later gluten exposure. IgG anti-tTG antibodies and EMA titres showed significant decreases (p<0.001) in treated patients. The frequency of IgG anti-tTG autoantibody positivity was 9.8% among IgA deficient blood donors and 11 of the 12 positive subjects with known HLA-DQ haplotypes carried DQ2 or DQ8 alleles. CONCLUSIONS: IgG anti-tTG and IgG EMA autoantibody tests are highly efficient in detecting coeliac disease in IgA deficient patients. The high prevalence of coeliac antibodies among symptom free IgA deficient blood donors who also carry coeliac-type HLA-DQ genes indicates that all IgA deficient persons should be evaluated for coeliac disease.

Autoantibodies↗
PubMed2002

Auditory adaptation is differentially impaired in familial and sporadic Alzheimer's disease.

Neurophysiologic measures are particularly sensitive to alterations in attention and arousal. The purpose of this study was to evaluate the auditory adaptation of normal and mildly demented elderly people. We compared the automatic behavior of an auditory evoked potential (N100) in three age-matched groups of elderly subjects, one with familial Alzheimer's disease (AD), one with sporadic AD and one healthy group. All AD subjects corresponded clinically and neuropsychologically with the early stage of dementia. The dynamic range of auditory adaptation is known to be related to age, and normal auditory adaptation for the age was observed in our healthy aged and sporadic AD subjects, whereas the familial AD subjects lacked normal adaptation. The familial AD subjects also showed statistically significantly smaller peak amplitudes and shorter latencies of the N100 throughout the habituation test. This persistent difference in automatic habituation of sensory responses supports the view that different subtypes of AD are differentially affected. The observed differences give an objective measure of the impaired involuntary adaptive functions of neuronal networks involved in auditory processing in subtypes of AD. Since habituation reflects the most primitive stage of learning and short-term memory, altered habituation may predict faster deterioration of clinical status in the familial group of AD subjects.

Adaptation, Physiological↗
PubMed2002

Genetic dissection between silent and clinically diagnosed symptomatic forms of coeliac disease in multiplex families.

BACKGROUND: Coeliac disease has a large variation in clinical outcome. In addition to the classical disease with malabsorption, many individuals have a silent form, in which subject symptoms are missing but autoantibodies and mucosa lesions are identical to the symptomatic disease. AIM: To investigate whether differences in HLA DR-DQ genes explain the variation in outcome. MATERIALS AND METHODS: HLA DQ alleles were determined in 28 multiplex families with sibling pairs in which one had the symptomatic disease but the other had the silent form. RESULTS: No differences in the distribution of HLA DR-DQ haplotypes could be observed. The clinically diagnosed coeliac disease seemed to have earlier onset than silent coeliac disease. CONCLUSIONS: Results indicate that the major genetic susceptibility locus, HLA DQ, does not determine the exact clinical outcome of coeliac disease.

Alleles↗
PubMed2002

Genetic dissection between coeliac disease and dermatitis herpetiformis in sib pairs.

Gluten sensitive enteropathy has various manifestations, of which the two major forms are classical coeliac disease (cCD) and dermatitis herpetiformis (DH). In cCD predominantly the small intestine is affected, whereas in DH also the skin is affected showing typical rash and IgA deposits. The symptoms in both forms are dependent on gluten intake. The factors diversifying these two clinical outcomes are unknown. In the present report we evaluated the role of the major genetic susceptibility locus, HLA DQ, in 25 families, in which both forms of the disease, cCD and DH, occurred in siblings. By using the family-based approach it can be assumed that within each family variation in environmental factors is substantially lower than in the standard case-control setting, and also the problems related to population stratification can be avoided. Results from the Finnish family material with 25 discordant and 85 concordant sib pairs, and from additional case-control material comprising 71 unrelated Hungarian DH and 68 cCD patients, together indicated that the HLA DQ locus did not differ between the two major outcomes of gluten sensitive enteropathy. The non-HLA DR;DQ factors are critical for the different clinical manifestations of gluten sensitivity.

Case-Control Studies↗
PubMed2002

CD80 (B7-1) and CD86 (B7-2) genes and genetic susceptibility to coeliac disease.

The role of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) in T-cell activation makes them good candidates for coeliac disease susceptibility genes. We conducted a genetic linkage study of the CD80/86 gene region in the general Finnish population and in a local subisolate. No linkage was found in either population.

Antigens, CD↗
PubMed2002

Not all HLA DR3 DQ2 haplotypes confer equal susceptibility to coeliac disease: transmission analysis in families.

BACKGROUND: HLA-DQ is the only established susceptibility factor for coeliac disease. We tested whether all HLA haplotypes with the known risk marker, HLA-DQ2, confer equal susceptibility to coeliac disease, i.e. whether haplotype transmission from DQ2 homozygous parents to patients is random. The random transmission would strengthen the importance of DQ2 as the only risk factor within the HLA region. METHODS: Inheritance of DQ2-positive haplotypes from parent to patients was investigated in 14 of 127 Finnish coeliac families who had an HLA-DQ2 homozygous parent. HLA alleles and 18 HLA-linked microsatellite markers were used to determine the haplotypes, which were divided into those transmitted and those non-transmitted from DQ2-homozygous parents to patients: RESULTS: Transmitted haplotypes differed clearly from those not transmitted. The alleles in the transmitted haplotypes were strongly conserved and predominantly consisted of the well-known HLA-A*01, B*08, DRB1*03, DQ2, DPB1*0101 haplotype. The non-transmitted haplotypes, on the other hand, were significantly more heterogeneous; in particular, markers near HLA-A and -B genes differed from the transmitted haplotypes. CONCLUSIONS: The results suggest that DQ2 is not the only HLA-linked genetic risk factor for coeliac disease but the conserved haplotype harbours at least one other risk gene.

Adult↗
PubMed2002

Coeliac disease among healthy members of multiple case coeliac disease families.

BACKGROUND: The main objective of the study was to assess the frequency of undetected coeliac disease among the first-degree relatives of families with two or more previously diagnosed coeliac disease patients. The value of the serum endomysial antibody test as a single means of detecting clinically silent coeliac disease was evaluated. The correlation of endomysial and tissue transglutaminase antibodies and the correlation of endomysial antibodies to the HLA typical for coeliac disease was determined. METHODS: A total of 137 multiple-case coeliac disease families with 872 family members were recruited; 466 healthy family members were simultaneously screened for gliadin and endomysial antibodies and thereafter for tissue tranglutaminase antibodies. Antibody-positive persons were typed for HLA-DQ2 and DQ8. The diagnosis of coeliac disease was based on the typical mucosal lesion on small-bowel biopsies. RESULTS: Forty-four (9.4%) of the healthy family members were positive for endomysial and 48 (10.3%) for gliadin antibodies; 42 biopsies revealed 29 new coeliac disease patients (6.2% of healthy individuals). Endomysial antibodies detected 97% and gliadin antibodies 52% of the new cases. All 44 endomysial-antibody-positive and 35 of 48 gliadin-antibody-positive individuals were positive for DQ2. Tissue transglutaminase antibodies corresponded well with endomysial antibodies. CONCLUSIONS: Undetected coeliac disease is common even among healthy first-degree relatives of multiple case families. The findings emphasize the value of serum endomysial antibodies in the detection of clinically silent coeliac disease. Endomysial-antibody-positive individuals, unlike gliadin-antibody-positive ones, share the coeliac disease-type HLA-DQ.

Adult↗
PubMed2002

Sevoflurane anaesthesia in children after induction of anaesthesia with midazolam and thiopental does not cause epileptiform EEG.

BACKGROUND: Sevoflurane is a methyl ether anaesthetic commonly used for induction and maintenance of general anaesthesia in children. Sevoflurane is a non-irritant and acts quickly so induction is usually calm. However, inhalation induction with high concentrations of sevoflurane can cause convulsion-like movements and seizure-like changes in the electroencephalogram (EEG). Little is known about the EEG during maintenance of anaesthesia with sevoflurane, so we planned a prospective trial of sevoflurane maintenance after i.v. induction with benzodiazepine and barbiturate, which is another common induction technique in children. METHODS: EEG recordings were made before premedication with midazolam (0.1 mg kg(-1) i.v.), during induction of anaesthesia with thiopental (5 mg kg(-1)), and during maintenance with sevoflurane (2% end-tidal concentration in air/oxygen without nitrous oxide) in 30 generally healthy, 3- to 8-year-old children having adenoids removed. Noise-free EEG data of good quality were successfully recorded from all 30 children. RESULTS: Two independent neurophysiologists did not detect epileptiform discharges in any of the recordings. CONCLUSION: Premedication with midazolam, i.v. induction with thiopental and maintenance of anaesthesia with 2% sevoflurane in air does not cause epileptiform EEG patterns in children.

Anesthesia, General↗
PubMed2002

Long term outcome of temporal lobe epilepsy surgery: analyses of 140 consecutive patients.

OBJECTIVE: To analyse the long term results of temporal lobe epilepsy surgery in a national epilepsy surgery centre for adults, and to evaluate preoperative factors predicting a good postoperative outcome on long term follow up. METHODS: Longitudinal follow up of 140 consecutive adult patients operated on for drug resistant temporal lobe epilepsy. RESULTS: 46% of patients with unilateral temporal lobe epilepsy became seizure-free, 10% had only postoperative auras, and 15% had rare seizures on follow up for (mean (SD)) 5.4 (2.6) years, range 0.25 to 10.5 years. The best outcome was after introduction of a standardised magnetic resonance (MR) imaging protocol (1993-99): in unilateral temporal lobe epilepsy, 52% of patients became seizure-free, 7% had only postoperative auras, and 17% had rare seizures (median follow up 3.8 years, range 0.25 to 6.5 years); in palliative cases (incomplete removal of focus), a reduction in seizures of at least 80% was achieved in 71% of cases (median follow up 3.1 years, range 1.1 to 6.8 years). Most seizure relapses (86%) occurred within one year of the operation, and outcome at one year did not differ from the long term outcome. Unilateral hippocampal atrophy with or without temporal cortical atrophy on qualitative MR imaging (p < 0.001, odds ratio (OR) 5.2, 95% confidence interval (CI) 2.0 to 13.7), other unitemporal structural lesions on qualitative MR imaging (p < or = 0.001, OR 6.9, 95% CI 2.2 to 21.5), onset of epilepsy before the age of five years (p < 0.05, OR 2.9, 95% CI 1.2 to 7.2), and focal seizures with ictal impairment of consciousness and focal ictal EEG as a predominant seizure type (p < 0.05, OR 3.4, 95% CI 1.2 to 9.1) predicted Engel I-II outcome. Hippocampal volume reduction of at least 1 SD from the mean of controls on the side of the seizure onset (p < 0.05, OR 3.1, 95% CI 1.1 to 9.2) also predicted Engel I-II outcome. CONCLUSIONS: Outcome at one year postoperatively is highly predictive of long term outcome after temporal lobe epilepsy surgery. Unitemporal MR imaging abnormalities, early onset of epilepsy, and seizure type predominance are factors associated with good postoperative outcome.

Adult↗
PubMed2001

Basicervical fracture--a rare type of hip fracture.

Basicervical fracture is a controversial type of hip fracture, which can be regarded as either extracapsular or intracapsular. It is seldom mentioned in the authorized orthopaedic textbooks, and it lacks an exact definition in the most commonly used classifications. The aim of this study was to evaluate the rate of basicervical hip fractures and the methods of treating them in a prospective series of 1624 consecutive hip fractures. Standardized forms were used to collect information, including the classification of fracture types. Initially, 108 fractures were classified as basicervical, but a careful second-look check revealed that 51 were transcervical fractures, while 27 fractures had a trochanteric extension. Thus, 30 of the fractures fulfilled the criteria of basicervical fracture (rate 1.8%). The 14 fractures treated as extracapsular fractures (dynamic hip screw, DHS, or gamma nail) showed a better outcome than the 16 treated as intracapsular fractures (hemiarthroplasty or screw osteosynthesis). We conclude that basicervical fracture of the hip is a very uncommon entity, but it is worth considering and should be treated as a trochanteric fracture.

Aged↗
PubMed2001

CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts.

BACKGROUND: Nasu-Hakola disease or polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a genetically heterogeneous disease characterized by a combination of systemic bone cysts and dementia. OBJECTIVE: The authors present a neurologic, neuroradiologic, and neuropathologic analysis of a series of PLOSL patients in which the diagnosis has been confirmed by molecular genetic methods. METHODS: Clinical, neurophysiologic, and imaging follow-up data on eight patients as well as autopsy samples of three patients were analyzed in this study. All eight patients were homozygous for a loss-of-function mutation in the DAP12 gene. RESULTS: In most patients, the disease debuted with pain in ankles and wrists after strain during the third decade, followed by fractures caused by cystic lesions in the bones of the extremities. Frontal lobe syndrome and dementia began to develop by age 30, leading to death by age 40. Neuroimaging disclosed abnormally high and progressively increasing bicaudate ratios and calcifications in the basal ganglia as well as increased signal intensities of the white matter on T2-weighted MR images even before the appearance of clinical neurologic symptoms. Three patients who had undergone autopsies showed an advanced sclerosing leukoencephalopathy with frontal accentuation, widespread activation of microglia, and microvascular changes. CONCLUSIONS: Although PLOSL in most patients manifests by bone fractures, some patients do not show any osseous symptoms and signs before the onset of neurologic manifestations. Consequently, patients with frontal-type dementia of unknown origin should be investigated by x-ray of ankles and wrists. The current results suggest early basal ganglia involvement in PLOSL.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Auditory event-related potentials differentiate patients with normal pressure hydrocephalus and patients with concomitant Alzheimer's disease verified by brain biopsy.

We studied 51 patients with clinical symptoms and CT findings suggesting normal pressure hydrocephalus (NPH). Tests included head MRI, auditory event-related potentials (ERPs), thorough neuropsychological testing and intraventricular intracranial 24 h pressure recording and infusion testing. A brain biopsy was also obtained to verify a concomitant dementing process (Alzheimer's disease; AD). Patients were divided into subgroups according to the need of shunt and the biopsy findings, and their ERPs were analysed blindly. The present results suggest that non-invasive ERPs aid in the differentiation of pure NPH from NPH with concomitant AD.

Aged↗
PubMed2001

Novel mutations in the human CYP21 gene.

The great majority of genetic defects underlying steroid 21-hydroxylase deficiency appear to result from intergenic recombinations between the homologous CYP21 and CYP21P genes. For a minority, novel sporadic point mutations have been detected. De novo mutations in CYP21 have also been reported, but only a few studies have systematically screened their occurrence. We here describe a population-based patient sample in order to estimate the rate of single-family (i.e. sporadic) and de novo germline mutations in the human CYP21 locus. Among 76 Finnish families were observed three single-family mutations and two de novo mutations in CYP21. The rates obtained, approximately 5% and approximately 2% for novel and de novo mutations, respectively, indicate that they are not rare and that their occurrence should not be ignored in genetic diagnostics of this disorder.

Adrenal Hyperplasia, Congenital↗
PubMed2001

SPECT and neuropsychological performance in severe depression treated with ECT.

BACKGROUND: In severe depression, studies of regional cerebral blood flow (rCBF) by SPECT have not produced uniform results. The association between changes in SPECT and electroconvulsive therapy (ECT) has shown somewhat conflicting data. No data are available on benzodiazepine receptor function SPECT studies in ECT. METHODS: Twenty drug-resistant adult inpatients fulfilling the DSM-IIIR criteria for major depression were studied by SPECT (rCBF by relative ECD uptake in all, and benzodiazepine receptor function by iomazenil uptake in five subjects) before and 1 week after clinically successful bitemporal ECT. Clinical and neuropsychological test scores were used as references for the possible changes in SPECT. RESULTS: An increased perfusion after ECT was observed in right temporal and bilateral parietal cortices, whereas no reductions in relative ECD uptake were seen after ECT. Iomazenil-SPECT revealed a highly significant increase in the benzodiazepine receptor uptake in all studied cortical regions except temporal cortices. CONCLUSIONS: Clinically successful ECT was associated with changes in vascular perfusion and GABAergic neurotransmission, providing new evidence for the mechanism of action of ECT and for the neurobiology of severe drug-resistant depression.

Adult↗