Search PubMed⌕ Search

Biomedical subjects

M Hakala

Publications and source records attributed to M Hakala.

At least 19 recordsLinked to original sources
PubMed2006

Compton scattering study of water versus ice Ih: intra- and intermolecular structure.

The hydrogen-bond geometries in water and polycrystalline ice Ih are studied using synchrotron radiation-based Compton scattering data of unprecedented statistical accuracy and consistency. By combining the experimental data with model calculations utilizing density functional theory, we show that the technique provides unique and complementary information on hydrogen bonding in water. The comparison of water and ice indicates the necessity of including a local intra-intermolecular geometric correlation for water, relating the intramolecular O-H bond length to the corresponding hydrogen-bond geometry. By using the hydrogen-bond geometries obeying this correlation, we demonstrate a further constraint on the angular distortions of the hydrogen bonds in water.

Journal Article↗
PubMed2006

Correlation of hydrogen bond lengths and angles in liquid water based on Compton scattering.

The temperature-dependent hydrogen-bond geometry in liquid water is studied by x-ray Compton scattering using synchrotron radiation combined with density functional theory analysis. Systematic changes, related to the weakening of hydrogen bonding, are observed in the shape of the Compton profile upon increasing the temperature. Using model calculations and published distribution functions of hydrogen-bond geometries obtained from a NMR study we find a significant correlation between the hydrogen-bond length and angle. This imposes a new constraint on the possible local structure distributions in liquid water. In particular, the angular distortions of the short hydrogen bonds are significantly restricted.

Journal Article↗
PubMed2006

Inhibitory characteristics of citrullinated telopeptides of type I and II collagens for autoantibody binding in patients with rheumatoid arthritis.

OBJECTIVE: To study how soluble citrullinated telopeptides of type I and II collagens inhibit the binding of autoantibodies to the respective antigens immobilized onto solid phase, and to use modifications of previous methods to re-analyse rheumatoid arthritis (RA) and control serum samples. METHODS: Autoantibody binding was inhibited with normal or citrullinated carboxytelopeptides using enzyme-linked immunosorbent assay (ELISA) methods. Serum samples were available from 120 patients with RA and 81 controls. RESULTS: Autoantibodies that bind normal C-telopeptides were not inhibited with soluble normal or citrullinated telopeptides. However, the antibodies that bind only citrullinated telopeptides could be inhibited with corresponding citrullinated telopeptides. Thus, it is not necessary to study the binding of autoantibodies to normal collagens if the specificity of their binding is assessed by immunological inhibition. For type I telopeptide, there are two arginines, the latter of which, when citrullinated, is important for binding. For type II telopeptide, there is one arginine, which is important when citrullinated. The other amino acids, e.g. the last alanine, have only a slight effect on binding. These improved methods differentiate better between RA patients, who have specific citrullinated autoantibodies, and controls than previous ELISA methods. CONCLUSIONS: Based on inhibition assay, it is possible to measure the autoantibodies binding specifically to citrullinated telopeptides of type I and II collagens. When only one assay is involved, variance is decreased and the overall performance is easier than before.

Adult↗
PubMed2006

Prognosis and mortality of polymyositis and dermatomyositis patients.

The objective of this study was to assess the long-term outcome of polymyositis (PM) and dermatomyositis (DM) and the factors predictive of this outcome in a nationwide series in Finland. One hundred and seventy-six patients with PM and 72 patients with DM diagnosed in Finland in 1969-1985 were selected from the national hospital discharge register according to the diagnostic criteria of Bohan and Peter and followed up until death or till the end of August 1995. Gender, age, delay of therapy, serum creatine kinase, erythrocyte sedimentation rate, initial dose of corticosteroids and duration of cytostatic therapy were assessed as factors prognostic of death. The 5-year survival rate for PM was 75% [95% confidence interval (CI): 68-81%] and that for DM 63% (50-73%), and the respective 10-year survival rates were 55% (47-62%) and 53% (41-64%). The median survival for polymyositis was 11.0 years (95% CI: 9.5-13.3) and that for DM 12.3 years (5.5-20.7). The standardized mortality ratio for the combined group of PM and DM showed approximately threefold mortality compared to the general population. Compared to PM patients, the subjects with DM had a 1.47-fold (95% CI: 0.99-2.12) age- and sex-adjusted risk of mortality. Except for age in both groups and the delay in diagnosis in the PM group, no other individual factor reached significance as a predictor of death. However, cancer had a hazard ratio (HR) of 2.16 for death (95% CI: 0.95-4.50) in the DM group and 1.99 (95% CI: 1.01-3.94) in the PM group. A comparison of the causes of death in the PM and DM groups showed that the patients with DM had a greater risk of dying from cancer (age-adjusted HR 5.11, 95% CI: 2.31-11.3). According to this nationwide analysis of survival and its prognostic factors in patients with PM and DM, the latter group had an increased age-adjusted risk for mortality compared to the former. The difference seems to be mostly explained by the fact that the patients with DM had a higher risk of dying from cancer.

Adrenal Cortex Hormones↗
PubMed2006

Parvovirus antibodies in vaccinated gilts in field conditions--results with HI and ELISA tests.

This study was conducted to determine the antibody response for porcine parvovirus (PPV) of 39 gilts in field conditions after vaccination. Gilts from four herds endemically infected with PPV were injected twice with a commercial vaccine of inactivated PPV and Erysipelothrix rhusiopathiae. The PPV antibodies were analysed both with haemagglutination inhibition (HI) and enzyme-linked immunosorbent assay (ELISA) in order to study the agreement between these methods. The possible association between high-antibody titres and reproductive failure (repeat breeding, culling for infertility, < or = 6 piglets born alive) was also investigated. In these study herds, endemically infected by PPV, most gilts (84.6%) had not seroconverted by the age of 6 months. On-field vaccination resulted in a consistent increase of humoral immunity not exceeding the antibody level of 1 : 512 in the majority of gilts in all herds examined. The agreement between ELISA and HI tests was moderate (Spearman's rho = 0.87, kappa = 0.63). The seroconversion over the level >1:512 by mid-pregnancy was not associated with reproductive failure.

Agglutination Tests↗
PubMed2005

Monetary value of lost productivity over a five year follow up in early rheumatoid arthritis estimated on the basis of official register data on patients' sickness absence and gross income: experience from the FIN-RACo trial.

OBJECTIVE: To explore the monetary value of rheumatoid arthritis related loss of productivity in patients with early active disease. METHODS: In a prospective cohort substudy of the FIN-RACo Trial, 162 patients with recent onset rheumatoid arthritis, aged 18 to 65 years and available to the workforce, were followed up for five years. Loss of work productivity in euros 2002 was estimated by data on absence for sickness and on income (human capital approach) from official databases. Treatment responses were evaluated by area under the curve (AUC) of the ACR-N measure and by increase in number of erosions in radiographs of hands and feet. The health assessment questionnaire (HAQ) at six months was linked to the International Classification of Functioning, Disability and Health (ICF). RESULTS: In all, 120 (75%) patients, women more often (82%) than men (61%) (p=0.002), lost work days. The mean lost productivity per patient-year was euro7217 (95% confidence interval (CI), 5561 to 9148): for women, euro6477 (4858 to 8536) and for men, euro8443 (5389 to 12,898). There was an inverse correlation with improvement: euro1101 (323 to 2156) and euro14 952 (10,662 to 19,852) for the highest and lowest quartiles of AUC of ARC-N, respectively. Lost productivity was associated with increase in the number of erosions and with disability in "changing and maintaining body position" subcategory of the ICF. CONCLUSIONS: Despite remission targeted treatment with disease modifying antirheumatic drugs, early rheumatoid arthritis results in substantial loss of productivity. A good improvement in the disease reduces the loss markedly.

Adolescent↗
PubMed2005

Grading of radiographic osteolytic changes after silastic metacarpophalangeal arthroplasty and a prospective trial of osteolysis following use of Swanson and Sutter prostheses.

The purpose of this study was to compare the incidence of radiographic osteolysis following insertion of 89 Swanson and 126 Sutter metacarpophalangeal implants in rheumatoid arthritis patients. The mean follow-up time in the two groups of patients was 57 (40-80) and 55 (36-79) months, respectively. This paper proposes a new method of classifying radiographic osteolysis. The remarkable number of osteolytic changes seen in the bones adjacent to MCP prostheses in this study would suggest that silastic prostheses should only be used when other surgical alternatives cannot be used and that long-term control by radiography be maintained after implantation of silicone prostheses into the MCP joint. In all grades of our classification, osteolysis was more frequent in the Sutter than in the Swanson group in this study, suggesting that use of the Sutter rather than the Swanson implant is questionable.

Aged↗
PubMed2005

Predictors of productivity loss in early rheumatoid arthritis: a 5 year follow up study.

OBJECTIVE: To explore baseline risk factors for productivity loss and work disability over 5 years in patients with early, active RA. PATIENTS AND METHODS: In the FIN-RACo trial, 195 patients with recent onset RA were randomised to receive either a combination of DMARDs with prednisolone or a single DMARD for 2 years. At baseline, 162 patients were working or available for work. After 5 years' follow up, data on sick leave and retirement were obtained from social insurance registers or case records. The cumulative duration of sick leaves and RA related disability pensions was counted for each patient. To analyse predictors of productivity loss, the patients were divided into four groups according to duration of work disability per patient year. RESULTS: Patient's and physician's global assessment of RA severity > or =50 and HAQ score > or =1.0 were risk factors for extension of productivity loss (OR (95% (CI) 1.77 (1.00 to 3.16), 1.85 (1.03 to 3.32), and 1.78 (1.01 to 3.14), respectively). Additional risk factors were low education level (2.40 (1.18 to 4.88)) and older age (1.03 (1.00 to 1.06)); combination treatment was a protective factor (0.59 (0.35 to 0.99)). CONCLUSION: At baseline, the risk of future productivity loss is best predicted by education level, age, global assessments of RA severity, and HAQ score.

Arthritis, Rheumatoid↗
PubMed2005

Are there autoantibodies reacting against citrullinated peptides derived from type I and type II collagens in patients with rheumatoid arthritis?

OBJECTIVES: To assess the possible presence in patients with rheumatoid arthritis (RA) of autoantibodies recognising citrullinated peptides derived from type I and II collagens. METHODS: Firstly, the binding of four pairs of synthetic peptides (arginine-containing and artificially citrullinated forms) related to different regions of human type II collagen were tested with sera from 120 patients with RA and 81 controls. Secondly, two similar pairs of peptides related to the carboxy terminal telopeptides of the alpha1 and alpha2 chains of human type I collagen were tested. RESULTS: 42-53% of the RA sera showed increased binding of arginine peptides related to type II collagen. However, 12 RA sera bound the citrullinated form of the alpha1(II) telopeptide more strongly than the corresponding arginine peptide. 20 RA sera bound the citrullinated carboxytelopeptide from the alpha1 chain of type I collagen (alpha1(I) telopeptide) more strongly than the respective arginine peptide. The correlation between the autoantibodies to type I and II collagen telopeptides was r(s) = 0.576, p < 0.001. Anti-cyclic citrullinated peptide (anti-CCP) assay was positive in 71/120 (59%) patients with RA. An anti-CCP assay detects a different subgroup of antibodies than anti-telopeptide assays. However, both anti-telopeptide and anti-CCP antibodies were increased in patients with RA. CONCLUSION: Some patients with RA were identified whose sera contained antibodies that specifically bound citrullinated peptides related to the carboxy terminal telopeptides of the alpha1 and alpha2 chains of type I collagen and the alpha1 chains of type II collagen (sequences YYXA, FYXA, and YMXA, where X stands for citrulline).

Adolescent↗
PubMed2004

Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis.

OBJECTIVE: A double blind, randomised, placebo controlled study to evaluate the safety and efficacy of etanercept to treat adult patients with ankylosing spondylitis (AS). METHODS: Adult patients with AS at 14 European sites were randomly assigned to 25 mg injections of etanercept or placebo twice weekly for 12 weeks. The primary efficacy end point was an improvement of at least 20% in patient reported symptoms, based on the multicomponent Assessments in Ankylosing Spondylitis (ASAS) response criteria (ASAS 20). Secondary end points included ASAS 50 and ASAS 70 responses and improved scores on individual components of ASAS, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), acute phase reactants, and spinal mobility tests. Safety was evaluated during scheduled visits. RESULTS: Of 84 patients enrolled, 45 received etanercept and 39 received placebo. Significantly more etanercept patients than placebo patients responded at the ASAS 20 level as early as week 2, and sustained differences were evident up to week 12. Significantly more etanercept patients reported ASAS 50 responses at all times and ASAS 70 responses at weeks 2, 4, and 8; reported lower composite and fatigue BASDAI scores; had lower acute phase reactant levels; and had improved spinal flexion. Etanercept was well tolerated. Most adverse events were mild to moderate; the only between-group difference was injection site reactions, which occurred significantly more often in etanercept patients. CONCLUSIONS: Etanercept is a well tolerated and effective treatment for reducing clinical symptoms and signs of AS.

Adult↗
PubMed2004

Contrast-enhanced dynamic and static MRI correlates with quantitative 99Tcm-labelled nanocolloid scintigraphy. Study of early rheumatoid arthritis patients.

OBJECTIVE: The aim of this study was to evaluate the roles of contrast-enhanced dynamic and static magnetic resonance imaging (MRI) and quantitative 99Tcm-labelled nanocolloid (NC) scintigraphy in detecting wrist joint inflammation in early rheumatoid arthritis (RA) patients. METHODS: Twenty-eight early RA patients (median symptom duration 5 months, range 1-12 months) underwent MRI, NC scintigraphy, laboratory and clinical examinations. Static wrist MRI scans were retrospectively scored for synovitis, bone oedema and erosions by two independent readers using the recently published rheumatoid arthritis MRI scoring system (RAMRIS). Twenty NC scans were analysed quantitatively by measuring maximum 99Tcm-NC uptake in three small areas of each wrist. From the same locations on the wrists, dynamic MRI gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhancement rates (E-rate) were measured. The average 99Tcm-NC uptake of the whole wrist region was also measured and average E-rates were calculated. Correlations between MRI and NC scintigraphy measurements were calculated. Correlations between imaging methods of the wrist and the global measures of inflammation (laboratory and clinical examinations) were also assessed. RESULTS: Strong correlations emerged between maximal 99Tcm-NC uptake and MRI E-rates, reflecting similar performance of the methods in detecting local synovial inflammation. 99Tcm-NC uptake and MRI E-rate correlated with semiquantitative scoring of synovitis and bone oedema from static MRI scans. The erythrocyte sedimentation rate (ESR) correlated with MRI scores, E-rate and 99Tcm-NC uptake. No correlation between the clinical parameters and the imaging methods was detected. Inter-observer reliability for scoring synovial hypertrophy, bone oedema and bone erosions from static MR images were high (single-measure fixed-effects intra-class correlations 0.87, 0.93 and 0.91 respectively). Intra-observer reliability for E-rate and 99Tcm-NC measurements of 10 randomly picked scans was found to be high, with an intra-class correlation of 0.92; 95% confidence interval (CI) 0.84-0.96 and 0.99; 95% CI 0.98-1.00, respectively. CONCLUSIONS: Objective information about wrist joint inflammation can be obtained with contrast-enhanced dynamic MRI and quantitative 99Tcm-labelled NC scintigraphy. MRI also allows visualization and semiquantitative scoring of bone oedema and erosions of the wrist. Dynamic MRI and NC scintigraphy are safe and easy to perform, and they can be used in a long-term follow-up of rheumatoid patients.

Adult↗
PubMed2004

Ultrasonography of salivary glands in primary Sjogren's syndrome. A comparison with magnetic resonance imaging and magnetic resonance sialography of parotid glands.

OBJECTIVES: To evaluate ultrasonography (US) of salivary glands in primary Sjögren's syndrome (SS) and to compare US with parotid magnetic resonance (MR) imaging and MR sialography. METHODS: US examination of parotid, submandibular and sublingual glands was performed on 27 patients with primary SS, 27 healthy controls and 27 symptomatic controls without SS. The results were compared with parotid MR imaging and MR sialography and the clinical features of the patients. RESULTS: Salivary gland abnormalities, parenchymal inhomogeneity or adipose degeneration, were visualized in 21 (78%) SS patients, in one healthy control and in two symptomatic controls by US. Eighteen (67%) patients had changes in the parotid and submandibular glands and 8 (30%) changes in the sublingual glands. In the comparison, MR sialography was found to be the most sensitive method (96%), followed by MR imaging (81%) and US (78%), in detecting glandular changes. The specificity of US was 94%. The US and MR results were related to anti-Ro/SSA positivity but not to saliva secretion. The focus scores were related only to parotid MR imaging findings. CONCLUSIONS: US, MR imaging and MR sialography with modern technology have reached such a good accuracy in visualizing glandular structural changes that they are promising alternatives to the conventional invasive examinations in the diagnostics of SS.

Adolescent↗
PubMed2004

HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis.

OBJECTIVES: To elucidate the contribution of HLA-DR-DQ haplotypes and their genotypic combinations to susceptibility to rheumatoid arthritis, and to evaluate the various models for HLA associated risk for the disease in a series of Finnish patients. METHODS: 322 Finnish patients with rheumatoid arthritis were typed for common north European HLA-DR-DQ haplotypes and compared with a series of 1244 artificial family based control haplotypes. RESULTS: The association of the so called shared epitope (SE) haplotypes (DRB1*0401, *0404, *0408, and *01) with rheumatoid arthritis was confirmed. The DRB1*0401 haplotypes carried a far stronger risk for the disease than the (DRB1*01/10)-(DQA1*01)-DQB1*0501 haplotypes. Seven protective HLA haplotypes--(DRB1*15)-(DQA1*01)-DQB1*0602; (DRB1*08)-(DQA1*04)-DQB1*04; (DRB1*11/12)-DQA1*05-DQB1*0301; (DRB1*1301)-(DQA1*01)-DQB1*0603; (DRB1*1302)-(DQA1*01)-DQB1*0604; (DRB1*07)-DQA1*0201-DQB1*0303; and (DRB1*16)- (DQA1*01)-DQB1*0502--were identified. In accordance with the reshaped shared epitope hypothesis, all the protective DRB1 alleles in these haplotypes share either isoleucine at position 67 or aspartic acid at position 70 in their third hypervariable region motif. However, differences in the disease risk of haplotypes carrying the same DR but different DQ alleles were also found: (DRB1*07)-DQA1*0201-DQB1*0303 was protective, while (DRB1*07)-DQA1*0201-DQB1*02 was neutral. The same haplotypes carried different risks for rheumatoid arthritis depending on their combination in genotypes. CONCLUSIONS: When assessing the influence of HLA genes on the susceptibility to rheumatoid arthritis, not only should the HLA-DR or -DQ alleles or haplotypes be unravelled but also the genotype. The effect of HLA class II region genes is more complicated than any of the existing hypotheses can explain.

Arthritis, Rheumatoid↗
PubMed2003

Validity of the Nottingham Health Profile in a Finnish out-patient population with rheumatoid arthritis.

OBJECTIVE: To assess the quality of life of 122 rheumatoid arthritis (RA) patients using the Nottingham Health Profile (NHP), which is a generic quality-of-life instrument, and to compare the results with those of 99 healthy local control subjects. METHODS: Our patient group represented consecutive out-patients from a central hospital. The NHP contains 38 items, each with a weighted score, that assess subjective distress on six dimensions: mobility, pain, energy, sleep, emotional reactions and social isolation. RESULTS: The median (age-adjusted) NHP scores for mobility, pain and energy showed statistically highly significant differences (P < 0.001) between the RA patients and the control group, indicating a poorer quality of life among the RA patients on all these dimensions. These NHP dimensions were also closely related to patients' experience of their overall health status. The NHP scores for sleep, emotional reaction and social isolation did not differ between the patients and the controls. CONCLUSION: The NHP, an instrument for assessing health-related quality of life, differentiated RA patients from local healthy individuals on the dimensions of mobility, energy and pain.

Adult↗
PubMed2002

Severe somatization in women is associated with altered cerebral glucose metabolism.

BACKGROUND: Somatization is a clinical phenomenon characterized by multiple, medically unexplained somatic symptoms. The pathophysiology remains unknown. We aimed to test the hypothesis of a central nervous system dysfunction in the pathophysiology of this disorder. METHOD: We studied 10 female patients diagnosed as having somatization disorder or undifferentiated somatoform disorder with no current Axis I disorders according to DSM-IV. They were compared with 17 healthy female volunteers using brain [18F]-fluorodeoxyglucose-PET with MRI reference. RESULTS: The patients had lower cerebral metabolism rates of glucose (P<0.05) in both caudate nuclei, left putamen and right precentral gyrus compared with healthy volunteers. CONCLUSIONS: This is the first study to demonstrate changes in brain metabolism in somatizing women. The regional cerebral hypometabolism is probably associated with the pathophysiology of somatization.

Adult↗
PubMed2002

Cognitive functioning in severe somatization--a pilot study.

OBJECTIVE: Somatizing patients often report cognitive complaints but neuropsychological research on somatization is scarce. We investigated somatizing patients for functioning in different cognitive domains. METHOD: Ten female patients with somatization disorder or undifferentiated somatoform disorder and 10 non-somatizing controls participated in neuropsychological examinations. RESULTS: The patients performed at a lower level than the controls in tests involving semantic memory, verbal episodic memory and visuo-spatial tasks, and were slower in attentional tasks. CONCLUSION: Somatization patients may suffer from substantial problems in cognitive performance.

Adult↗
PubMed2001

Identification of a novel common genetic risk factor for lumbar disk disease.

CONTEXT: Lumbar disk disease (LDD) is one of the most common musculoskeletal diseases, with a prevalence of about 5%. A tryptophan (Trp) allele (Trp2) was recently discovered in the COL9A2 gene that is associated with dominantly inherited LDD but is only present in about 4% of Finnish patients with LDD. OBJECTIVE: To determine if other collagen IX gene sequence variations play a role in the pathogenesis of LDD. DESIGN AND SETTING: Case-control study conducted from February 1997 to May 1998 at university hospitals in Finland. PARTICIPANTS: A total of 171 individuals with LDD (evaluated clinically and by magnetic resonance imaging or computed tomography) and 321 controls without LDD (186 healthy individuals, 83 patients with primary osteoarthritis, 31 with rheumatoid arthritis, and 21 with chondrodysplasias). MAIN OUTCOME MEASURES: Frequencies of sequence variations covering the entire coding sequences and exon boundaries of the collagen IX genes, COL9A1, COL9A2, and COL9A3, which code for the alpha1, alpha2, and alpha3 chains of the protein, detected by conformation-sensitive gel electrophoresis and confirmed by sequencing, compared between individuals with and without LDD. RESULTS: Mutation analysis of all 3 collagen IX genes resulted in identification of an Arg103-->Trp (arginine-->tryptophan) substitution in the alpha3 chain (Trp3 allele). The frequency of the Trp3 allele was 12.2% in LDD cases, excluding 7 individuals who were carriers of the previously identified Gln326-->Trp (glutamine-->tryptophan) substitution in the alpha2 chain (Trp2 allele), and was 4.7% among controls. The difference in the frequency was statistically significant (P =.000013). Presence of at least 1 Trp3 allele increases risk of LDD about 3-fold. CONCLUSION: This study led to the identification of a novel common genetic risk factor for LDD, confirming that genetic risk factors likely play a significant role in LDD.

Adult↗