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Biomedical subjects

O Mäki-Ikola

Publications and source records attributed to O Mäki-Ikola.

At least 19 recordsLinked to original sources
PubMed2006

Selegiline slows the progression of the symptoms of Parkinson disease.

OBJECTIVE: To study the long-term effects of selegiline in monotherapy and in combination with levodopa in the early phase of Parkinson disease (PD). METHODS: One hundred fifty-seven de novo PD patients were randomized in a double-blind, placebo-controlled study of 7 years' duration. In the monotherapy part, selegiline significantly delayed the initiation of levodopa therapy vs placebo. The authors now report the results from the combination part of the study, in which 140 patients received selegiline or placebo in addition to individually tailored levodopa therapy. RESULTS: Compared with placebo, selegiline slowed the progression of disease disability as measured by the Unified Parkinson Disease Rating Scale (UPDRS) total score (p = 0.003) or by motor (p = 0.002) and Activities of Daily Living (p = 0.0002) subscores. After 5 years in combination therapy, the mean difference in the UPDRS total score was nearly 10 points, with patients receiving placebo having 35% higher scores. Simultaneously, patients receiving placebo needed progressively higher doses of levodopa than patients receiving selegiline; after 5 years, the mean dosage of levodopa was 19% higher with placebo than with selegiline (p = 0.0002). Considering the entire (monotherapy and combination therapy) 7-year study time, there was a trend for selegiline to delay the start of wearing-off fluctuations (hazard ratio 0.55, p = 0.08). In both phases of the study, selegiline was safe and well tolerated. CONCLUSIONS: The results of this long-term study confirm earlier findings indicating that selegiline delays the progression of the signs and symptoms of Parkinson disease.

Activities of Daily Living↗
PubMed1999

Enterobacterial infection modulates major histocompatibility complex class I expression on mononuclear cells.

Major histocompatibility complex (MHC) class I expression is reduced in several viral infections, but it is not known whether the same happens during infections caused by intracellular enterobacteria. In this study, the expression of MHC class I antigens on peripheral blood mononuclear cells (PBMC) from 16 patients with Salmonella, Yersinia, or Klebsiella infection was investigated. During or after the acute infection, the expression of MHC class I antigens was markedly decreased in eight patients, all with genotype HLA-B27, and six out of eight with reactive arthritis (ReA). A significant decrease of monomorphic MHC class I was found in three patients, of HLA-B27 in eight (P<0.05) and of HLA-A2 in two. However, patients negative for the HLA-B27 genotype, or healthy HLA-B27-positive individuals, did not have a significant decrease of MHC class I antigens. During the decreased expression on the cell surface, intracellular retention of MHC class I antigens was observed, whereas HLA-B27 mRNA levels did not vary significantly. This is the first evidence that enterobacterial infection may down-regulate expression of MHC class I molecules in vivo and that down-regulation is predominant in patients with the HLA-B27 genotype.

Adolescent↗
PubMed1998

Increased synovial endothelium binding and transendothelial migration of mononuclear cells during Salmonella infection.

OBJECTIVE: To investigate the adhesion and extravasation capacity of peripheral blood mononuclear cells (PBMC) and the transport of bacterial antigens within these cells during Salmonella infection. METHODS: Thirteen patients who were part of 2 outbreaks of Salmonella enteritidis infection were included in this study. The capacity of PBMC from these patients to bind to vascular endothelium in inflamed synovium was tested using a Stamper-Woodruff-type frozen-section assay. The same cells were studied for the presence of Salmonella antigens by immunofluorescence staining. The transendothelial migration of mononuclear cells containing Salmonella or its components through unstimulated endothelial cell layer was quantified. RESULTS: The capacity of PBMC to adhere to synovial vessels was significantly increased during Salmonella infection (P=0.0003). Monocytes had a transiently high adhesive state between 2 and 5 weeks after the patients had eaten the contaminated food. The cells containing Salmonella antigens were concentrated in the transmigrated population. CONCLUSION: During acute Salmonella infection the increased binding of PBMC to vascular endothelium in inflamed synovium and enhanced transmigration of PBMC containing Salmonella may be the key factors leading to transport of bacterial antigens through the endothelial barrier and initiation of arthritis in susceptible individuals.

Adult↗
PubMed1998

Selegiline delays the onset of disability in de novo parkinsonian patients. Swedish Parkinson Study Group.

OBJECTIVE: The objective of this study was to investigate the effect of selegiline first as monotherapy and then in combination with levodopa in the early phase of PD. METHODS: A total of 157 de novo PD patients were randomized to receive either selegiline or placebo in a double-blind study until levodopa therapy became necessary. Thereafter, the drugs were withdrawn for an 8-week washout period to evaluate the possible symptomatic effect of selegiline. RESULTS: Analysis of Kaplan-Meier survival curves for each group showed that selegiline delayed significantly the need for levodopa therapy (p = 0.028). The semiannual rate of disability progression was slowed down significantly in the selegiline group analyzed with the Unified Parkinson's Disease Rating Scale (total and motor scores; p < 0.001). Selegiline had a "wash-in" effect (i.e., an initial symptomatic amelioration of PD at 6 weeks and 3 months). However, after the 8-week washout period, no significant differences in the deterioration of disability between the groups was revealed in any of the scales, suggesting that besides having a slight symptomatic effect, selegiline may also have neuroprotective effects. Similarly, the progression of symptoms from baseline to the end of the washout period was significantly slower (p = 0.033) in the selegiline group when the progression was adjusted by the time to reach the end point. Selegiline was well tolerated. CONCLUSIONS: Selegiline delayed significantly the need to start levodopa in early PD. After a 2-month washout period (before the start of levodopa therapy) no significant symptomatic effect of selegiline was seen in comparison with the placebo group, supporting the concept of neuroprotective properties of the drug.

Aged↗
PubMed1998

Effect of selegiline on mortality in patients with Parkinson's disease: a meta-analysis.

INTRODUCTION: The Parkinson's Disease Research Group of the United Kingdom (PDRG-UK) reported increased mortality in PD patients treated with levodopa plus selegiline compared with those treated with levodopa alone. METHODS: We performed a meta-analysis on five long-term, prospective, randomized trials of selegiline in patients with untreated PD. Included in the analysis were four randomized, double-blind, placebo-controlled studies and one randomized, double-blind, placebo-controlled study of 2 years' duration followed by long-term, open follow-up. RESULTS: The mean duration of follow-up was 4.1 +/- 1.8 years. There were 14 deaths in 297 selegiline-treated patients (4.7%) and 17 deaths in 292 non-selegiline-treated patients (5.8%). The hazard ratio for mortality was 1.02 (95% CI 0.44 to 2.37; p = 0.96). An analysis restricted to patients receiving only levodopa with or without selegiline noted 11 deaths in 257 levodopa/selegiline-treated patients (4.3%) and 11 deaths in 254 patients treated with levodopa alone (4.3%). The hazard ratio was 1.06 (95% CI 0.44 to 2.55; p = 0.90). Death rate per 1,000 patient years was 11.4 in the selegiline group and 14.2 in the nonselegiline group. Kaplan-Meier survival curves reflecting pooled survival data showed no significant difference in duration of survival. The hazard ratio was 0.84 (95% CI 0.41 to 1.70; p = 0.63) for selegiline- versus non-selegiline-treated patients and 1.05 (95% CI 0.46 to 2.43; p = 0.91) for selegiline/levodopa- versus levodopa-treated patients. CONCLUSION: These results contrast with those of the PDRG-UK study and demonstrate no increase in mortality associated with selegiline treatment whether or not patients also received levodopa.

Aged↗
PubMed1998

IgA class serum antibodies against three different Klebsiella serotypes in ankylosing spondylitis.

OBJECTIVE: To investigate the possible predominance of certain Klebsiella pneumoniae capsular types in the pathogenesis of ankylosing spondylitis (AS). METHODS: The prevalence of IgA class antibodies against three different K. pneumoniae strains (with capsular types 21, 30 and 43) was studied in the sera of 177 patients with AS and of 100 healthy blood donors using an enzyme-linked immunosorbent assay. RESULTS: The median Klebsiella-specific antibody levels were always higher in patients than in controls regardless of the serotype used as antigen. When the prevalence of increased antibody levels was compared between the groups, it was highest against the strain with capsular type 30, whereas against strains 21 and 43 it was similar among patients and controls. CONCLUSIONS: A broad range of Klebsiella serotypes may be involved in the pathogenesis of AS. Thus, it is important to take the different Klebsiella serotypes into particular account in these studies.

Adult↗
PubMed1997

High frequency of Yersinia antibodies in healthy populations in Finland and Germany.

Sera from 94 healthy Finnish and 100 healthy German blood donors were studied for Yersinia enterocolitica antibodies by two different techniques, enzyme immunoassay and immunoblotting, to compare the frequency of Yersinia infections in Finnish and German populations. The prevalence of Yersinia antibodies in Finland (19% and 31% by enzyme immunoassay and immunoblotting, respectively) and in Germany (33%, 43%) is relatively high and may indicate many subclinical Yersinia infections in healthy populations. Postinfectious complications, such as reactive arthritis, may follow also such subclinical infection; sensitive serological tests are important in their diagnosis.

Adolescent↗
PubMed1997

IgM, IgG and IgA class enterobacterial antibodies in serum and synovial fluid in patients with ankylosing spondylitis and rheumatoid arthritis.

IgM, IgG and IgA class antibodies against three Klebsiella pneumoniae capsular types, Escherichia coli and Proteus mirabilis, as well as total immunoglobulin concentrations, were measured by enzyme immunoassay and radial immunodiffusion technique, respectively, in paired serum and synovial fluid samples from eight patients with ankylosing spondylitis and 10 with rheumatoid arthritis. No clear evidence for intra-articular antibody production against any of the studied microbes was found.

Adult↗
PubMed1997

Lack of adverse interactions between concomitantly administered selegiline and citalopram.

We have evaluated the risk for pharmacokinetic and/or pharmacodynamic interactions of concomitantly administered selegiline, a selective monoamine oxidase type B inhibitor, and citalopram, a widely used selective serotonin uptake inhibitor antidepressant. Two parallel groups of healthy volunteers received 20 mg of citalopram (n = 12) or placebo (n = 6) once daily for 10 days in a randomized, double-blind fashion, followed by concomitant selegiline 10 mg once daily for 4 days. The safety of this drug combination was assessed by measurements of blood pressure, heart rate, body temperature, and inquiries for adverse events. Blood samples were taken for the analysis of serum concentrations of both study drugs and their metabolites and plasma prolactin, adrenaline, noradrenaline, and 3,4-dihydroxyphenylglycol (DHPG); urinary excretion of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were assessed. After a 5-week washout, the 12 subjects who took citalopram in the first part of the study received 10 mg of selegiline once daily for 4 days to compare the pharmacokinetics of selegiline with and without concomitant citalopram. The safety analysis showed no significant differences in vital signs or the frequency of adverse events between the study groups. Plasma prolactin concentrations were increased by 40% after 10 days' treatment with citalopram (p = 0.03); this was not potentiated by concomitantly administered selegiline. The comparison of plasma concentrations of noradrenaline, adrenaline, and DHPG and the amount of serotonin and 5-HIAA excreted into urine between the study groups indicated no signs of subclinical pharmacodynamic interaction between selegiline and citalopram. The relative bioavailability of selegiline was slightly reduced (by 29%; p = 0.008) when citalopram was coadministered compared with selegiline alone. However, no indication of a pharmacokinetic interaction was found in the analysis of serum concentrations of the three main metabolites of selegiline. The pharmacokinetics of citalopram remained unaffected by concomitant selegiline. The present results indicate lack of clinically relevant pharmacodynamic or pharmacokinetic interactions between selegiline and citalopram.

Adult↗
PubMed1997

Selegiline as the primary treatment of Parkinson's disease--a long-term double-blind study.

INTRODUCTION: To assess the therapeutic efficacy of selegiline combined with levodopa in the long-term treatment of Parkinson's disease (PD). MATERIAL AND METHODS: A randomized, prospective, double-blind study on 44 patients with PD needing levodopa therapy after the initial double-blind treatment with placebo or selegiline was carried out. The patients were followed-up for 5 years under combination therapy. RESULTS: Selegiline induced a significant (P < 0.001) slowing in the need to increase the daily levodopa dose in order to compensate for the progression of the disease. After 5 years of combination therapy the mean dose of levodopa was on average 320 mg lower in the selegiline group (405 +/- 59 mg vs 725 +/- 78 mg). The difference in the levodopa doses between the two groups increased along with follow-up time, as also the ratio of the levodopa doses (placebo/selegiline group). The number of daily levodopa doses needed to compensate for the occurrence of motor fluctuations was significantly lower in the selegiline group. The parkinsonian disability did not differ between the two groups because the clinical condition was kept as optimal as possible by adjusting the levodopa dosage. Nine patients in the placebo group needed initiation of additional dopaminergic therapy in comparison to one in the selegiline group (P = 0.004). During the 5-year follow-up period 11 patients were withdrawn from the selegiline group, 7 due to adverse events. There was no difference in mortality between the two groups. CONCLUSIONS: Selegiline therapy offers beneficial long-term effets in the treatment of PD.

Antiparkinson Agents↗
PubMed1997

Association of gut inflammation with increased serum IgA class Klebsiella antibody concentrations in patients with axial ankylosing spondylitis (AS): implication for different aetiopathogenetic mechanisms for axial and peripheral AS?

OBJECTIVES: A role for Klebsiella pneumoniae in ankylosing spondylitis (AS) has been suggested because faecal carriage of Klebsiella and serum Klebsiella specific antibodies may be increased in this disease. This study has extended the earlier findings by comparing Klebsiella specific serum IgA class antibodies with inflammatory changes in the gut. METHODS: IgA antibodies to K pneumoniae, Escherichia coli, and Proteus mirabilis in serum samples of 25 patients with AS, of eight control patients, and of 100 healthy blood donors were measured by enzyme immunoassay. Gut inflammation of the patients was studied by ileocolonoscopy. RESULTS: Increased IgA antibody concentrations to K pneumoniae associated with gut inflammation in patients with axial form of AS. Such association was not seen in patients with peripheral form of AS. CONCLUSIONS: These findings may provide further evidence for the role of K pneumoniae in the pathogenesis of AS. However, at least some of the patients with axial AS without gut inflammation, as well as patients with peripheral AS did not have increased K pneumoniae antibody concentrations, which may be regarded as evidence against the direct role of K pneumoniae in the pathogenesis. The aetiopathogenetic mechanisms in the axial and peripheral form of AS may be different.

Antibodies, Bacterial↗
PubMed1997

Enhanced jejunal production of antibodies to Klebsiella and other Enterobacteria in patients with ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVE: To measure gut immunity directly in jejunal fluid in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). METHODS: Antibodies against three different Enterobacterias were measured in jejunal perfusion fluids (collected by a double balloon perfusion device) of 19 patients with AS, 14 patients with RA, and 22 healthy controls using enzyme linked immunosorbent assay. RESULTS: The AS patients had significantly increased jejunal fluid concentrations of IgM, IgG, and IgA class antibodies against Klebsiella pneumoniae, and IgM and IgA class antibodies against Escherichia coli and Proteus mirabilis compared with healthy controls. When compared with the patients with RA, the AS patients had higher concentrations of IgA and IgG class antibodies only against K pneumoniae. The RA patients had higher IgM class antibody concentrations against all three studied Enterobacterias, when compared with the healthy controls, suggesting an enhanced mucosal immune response in these patients. A three month treatment with sulphasalazine did not decrease enterobacterial antibody concentrations in the 10 patients with AS. CONCLUSION: There is strong direct evidence for an abnormal mucosal humoral immune response particularly to K pneumoniae in patients with AS.

Adult↗
PubMed1996

Similarly increased serum IgA1 and IgA2 subclass antibody levels against Klebsiella pneumoniae bacteria in ankylosing spondylitis patients with/without extra-articular features.

IgA1 and IgA2 subclass serum antibodies against whole Klebsiella pneumoniae bacteria were studied earlier in the sera of 98 patients with ankylosing spondylitis (AS) and in 100 healthy blood donors by enzyme immunoassay. In this study, the patients were divided into groups according to the clinical picture, i.e., the presence or absence of iritis and enthesitis. The previous findings of increased IgA1 and IgA2 subclass antibody levels against K. pneumoniae in AS patients when compared to the healthy controls were not specifically associated with any single AS patient group in the present study, but instead were similarly seen in all patient groups with/without extra-articular features. This is in line with the previous studies suggesting a role for K. pneumoniae in the pathogenesis of AS.

Adolescent↗