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Biomedical subjects

M Färkkilä

Publications and source records attributed to M Färkkilä.

At least 19 recordsLinked to original sources
PubMed2007

Almotriptan and zolmitriptan in the acute treatment of migraine.

OBJECTIVE: To compare almotriptan and zolmitriptan in the treatment of acute migraine. METHODS: This multicentre, double-blind trial randomized adult migraineurs to almotriptan 12.5 mg (n = 532) or zolmitriptan 2.5 mg (n = 530) for the treatment of a single migraine attack. The primary end point was sustained pain free plus no adverse events (SNAE); other end points included pain relief and pain free at several time points, sustained pain free, headache recurrence, use of rescue medication, functional impairment, time lost because of migraine, treatment acceptability, and overall treatment satisfaction. RESULTS: No significant difference was seen in SNAE (almotriptan 29.2% vs zolmitriptan 31.8%) or the other efficacy end points measured. The incidence of triptan-associated AEs and triptan-associated central nervous system AEs was significantly lower for patients receiving almotriptan compared to zolmitriptan. CONCLUSIONS: Almotriptan and zolmitriptan were associated with similar efficacy and overall tolerability in the treatment of acute migraine. Almotriptan was associated with a significantly lower rate of triptan-associated AEs.

Acute Disease↗
PubMed2006

Pharmacokinetics and bone effects of budesonide in primary biliary cirrhosis.

BACKGROUND/AIM: To evaluate the safety of budesonide in primary biliary cirrhosis. METHODS: 77 primary biliary cirrhosis patients, with stages I-III at entry, were randomized to use either budesonide 6 mg and ursodeoxycholic acid 15 mg/kg (group A), or ursodeoxycholic acid alone (group B) daily for 3 years. In 22 patients, budesonide pharmacokinetics was determined after 3 years. Bone mass density was measured in 62 patients at baseline and 3 years; in 57 patients also liver biopsies were performed. RESULTS: At 3 years, no significant differences in the pharmacokinetics of budesonide were found between the patients with stages 0-I, II and III primary biliary cirrhosis. In group A, bone mass density in femoral neck and lumbar spine were decreased by 3.6% (P = 0.0002) and 2.8% (P = 0.003) from the baseline. In group B, the corresponding decreases were 1.9% (P = 0.029) and 0.7% (P = 0.25), but the differences between the groups were not statistically significant (P = 0.16 for femoral neck and P = 0.08 for lumbar spine). CONCLUSIONS: The plasma concentrations of budesonide do not significantly differ within stages I-III primary biliary cirrhosis patients. The combination of budesonide and ursodeoxycholic acid may decrease bone mass density in the femoral neck and lumbar spine in some primary biliary cirrhosis patients, and bone mass density is recommended to be monitored during budesonide therapy.

Anti-Inflammatory Agents↗
PubMed2006

Intra-abdominal abscess in a patient with tumour necrosis factor receptor-associated periodic syndrome.

Tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autoinflammatory disorder characterized by periodic attacks of fever and inflammation, due to mutations in the gene coding for the TNF type I receptor (TNFRSF1A). A 16-year-old patient with the diagnosis of TRAPS was admitted to hospital because of fever and abdominal pain. Initially, the symptoms were interpreted as manifestations of another TRAPS attack, but the patient's condition worsened, despite treatment with corticosteroids and antibiotics. A repeated computer tomography revealed an intra-abdominal abscess, which necessitated urgent surgical intervention. This case stresses the importance of differential diagnostic vigilance when dealing with patients with rare genetic diseases.

Abdominal Abscess↗
PubMed2006

Testing of variants of the MTHFR and ESR1 genes in 1798 Finnish individuals fails to confirm the association with migraine with aura.

Among the few independently replicated genetic associations in migraine are polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and oestrogen receptor (ESR1) genes. We studied the contribution of these genes to migraine susceptibility by genotyping six MTHFR and 26 ESR1 polymorphisms in 898 unrelated migraine with aura (MA) patients and in 900 unrelated healthy controls. There were no differences in the genotype distributions of the previously migraine-associated SNPs C677T (MTHFR) and G2014A (ESR1) between cases and controls (P-values 0.83 and 0.55, respectively). Thus, we were not able to replicate the previous findings, although our study had considerable power. However, five of the ESR1 SNPs (rs6557170, rs2347867, rs6557171, rs4870062 and rs1801132) that were in strong linkage disequilibrium were nominally associated with MA (uncorrected P-values 0.007-0.034). These results did not, however, remain significant after taking multiple testing into account. Thus it seems unlikely that the studied genes are involved in migraine susceptibility, at least in this sample.

Estrogen Receptor alpha↗
PubMed2005

A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention.

BACKGROUND: Irritable bowel syndrome is a gastrointestinal disorder of unknown aetiology. The effect of probiotics in this syndrome remains unclear. AIM: To investigate whether a probiotic mixture containing Lactobacillus rhamnosus GG, L. rhamnosus LC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii ssp. shermanii JS is effective in alleviating irritable bowel syndrome symptoms. METHODS: A total of 103 patients fulfilling the Rome I or II criteria took part in this 6-month, randomized, double-blind placebo-controlled trial. The patients received a probiotic capsule or a placebo capsule daily. Gastrointestinal symptoms and bowel habits were recorded. RESULTS: At the end the total symptom score (abdominal pain + distension + flatulence + borborygmi) was 7.7 (95% CI: -13.9 to -1.6) points lower in the probiotic group (P = 0.015). This represents a median reduction of 42% in the symptom score of the probiotic group compared with 6% in the placebo group. In individual symptoms, borborygmi was milder in the probiotic group (P = 0.008), and for the rest of the symptoms there was a non-significant trend. CONCLUSIONS: The results indicate that this probiotic mixture is effective in alleviating irritable bowel syndrome symptoms. Considering the high prevalence of irritable bowel syndrome and the lack of effective therapies, even a slight reduction in symptoms could have positive public health consequences.

Adult↗
PubMed2005

Decreased cerebellar total creatine in episodic ataxia type 2: a 1H MRS study.

Episodic ataxia type 2 (EA2) affects mainly the cerebellum via mutations in the CACNA1A gene. The authors used proton MR spectroscopy to examine cerebellar and thalamic metabolism of nine mostly nonataxic EA2 family members (all with proven CACNA1A mutation) and nine healthy control subjects. Cerebellar total creatine was lower in the patient group (p = 0.005) than in control subjects, possibly reflecting an early sign of calcium channel dysfunction in EA2.

Adolescent↗
PubMed2005

Comparative tolerance of IFN beta-1a regimens in patients with relapsing multiple sclerosis. The EVIDENCE study.

The EVIDENCE study was a direct comparative study of two dose regimens of interferon (IFN) beta-1a used in the treatment of relapsing-remitting multiple sclerosis (RRMS): 30 mcg intramuscularly once weekly (qw; n=338) and 44 mcg subcutaneously three times weekly (tiw; n=339). The study continued for an average of 64 weeks. The safety population consisted of all patients receiving at least one dose of study drug. Clinical assessments occurred every 4 weeks for 24 weeks and then every 12 weeks. Blood tests for safety were taken at baseline and at weeks 4 and 12, and every 12 weeks thereafter. Overall adverse events were more common with the 44 mcg tiw regimen (p=0.007), and were due predominantly to differences in injection-site reactions. The majority of adverse events were rated mild by investigators. Hepatic and haematological adverse events and asymptomatic laboratory abnormalities were more common with 44 mcg tiw (p<0.001),with no difference seen for severe events. Flu-like symptoms were more common with 30 mcg qw (p=0.031), were more severe and persisted for longer. Serious adverse events were comparable for both groups, as were drug discontinuations. In conclusion, although adverse events were more common with high-dose, high-frequency IFN therapy, differences were primarily for mild events and did not affect treatment adherence. Based on superior clinical and magnetic resonance imaging outcomes over an average of 64 weeks, coupled with modest safety differences, the risk-benefit ratio for IFN therapy in RRMS favours the 44 mcg tiw regimen over this period of time.

Central Nervous System↗
PubMed2005

The efficacy of glatiramer acetate in beta-interferon-intolerant MS patients.

OBJECTIVES: Glatiramer acetate (GA) is routinely used in multiple sclerosis (MS) patients who cannot tolerate or fail to respond to beta-interferon (IFN-beta). The aim of this study was to assess the efficacy and tolerability of GA in these patients. METHODS: Fifteen relapsing-remitting MS patients who had discontinued IFN-beta therapy due to side effects were included in this open, 1-year prospective study. Neurologic examinations and laboratory assessments were performed every 3 months. The induction of MxA protein production was also evaluated. RESULTS: Eleven of fifteen patients (73%) tolerated GA well whereas four patients (27%) discontinued treatment due to side effects. The relapse rate reduced from 1.86 per year to 0.91 per year. Neither laboratory abnormalities nor MxA protein induction was found. CONCLUSION: GA can be considered as a good treatment alternative to IFN-beta-intolerant MS patients. However, some patients were not able to use available immunomodulative treatments, which emphasizes the need for new therapeutic options. The lack of MxA protein induction confirms the different mechanisms of action of GA and IFN-beta.

Adjuvants, Immunologic↗
PubMed2004

A novel missense ATP1A2 mutation in a Finnish family with familial hemiplegic migraine type 2.

Familial hemiplegic migraine (FHM), a rare autosomal dominant subtype of migraine with aura, has been linked to two chromosomal loci, 19p13 and 1q23. Mutations in the Na+K+-ATPase alpha2 subunit gene, ATP1A2, on 1q23 have recently been shown to cause familial hemiplegic migraine type 2 (FHM2). We sequenced the coding regions of this gene in a Finnish chromosome 1q23-linked FHM family with associated symptoms such as coma and identified a novel A1033G mutation in exon 9. This mutation results in a threonine-to-alanine substitution at codon 345. This residue is located in a highly conserved N-terminal region of the M4-5 loop of the Na+,K+-ATPase. Furthermore, the T345A mutation co-segregated with the disorder in our family and was not present in 132 healthy Finnish control individuals. For these reasons it is most likely the FHM-causing mutation in this family.

Amino Acid Sequence↗
PubMed2004

Boron biodistribution in beagles after intravenous infusion of 4-dihydroxyborylphenylalanine-fructose complex.

Boron biodistribution after intravenous infusion of 4-dihydroxyborylphenylalanine-fructose (BPA-F) complex was investigated in six dogs. Blood samples were evaluated during and following doses of 205 and 250 mg/kgbw BPA in a 30 min infusion, and 500 mg/kgbw in a 1h infusion. Samples from whole blood, urine, brain and other organs were analysed for boron content after varying times following the onset of infusion. The whole blood boron concentrations declined from 27 to 8.4 ppm over the period of 39-165 min after the onset of infusion and the levels increased from 1.9 to 12 ppm in the grey matter of the brain over the same period. The boron concentrations in whole blood decreased steadily, whereas the boron values in brain tissue rose steadily with time. It was concluded that whole blood boron concentrations do not seem to reflect accurately the boron concentration in brain tissue at respective time points.

Animals↗
PubMed2004

Cost-benefit analysis of Helicobacter pylori screening.

BACKGROUND: Helicobacter pylori screening may markedly reduce mortality and morbidity in the decades ahead. AIMS: This study explores the costs and benefits of population-based H. pylori screening in terms of health care cost taking into account all relevant H. pylori-related diseases. MATERIAL AND METHODS: The computer-based decision analysis compared two strategies: (1) screen for H. pylori and treat those individuals who test positive, and (2) do not screen for H. pylori, and test and treat H. pylori only if related clinical symptoms appear. The model estimated the discounted H. pylori-related accumulative health care costs from screening age to death in both strategies. The baseline case estimates cost-benefit for screenees aged 15-45 years. The main outcome measure is the incremental health care cost per case in the screening compared with the no-screening alternative. The probability estimates were obtained from the Finnish Vammala H. pylori screen and treat project, including 5288 subjects in the years 1996-1998, published studies, national statistics and hospitals' internal accounts. RESULTS: The incremental cost per case was 26 US dollars in the screening compared with the no-screening alternative. It was lowest in the group aged 45 years, where H. pylori screening showed cost savings per case. CONCLUSIONS: H. pylori screening is more favourable in the older age cohorts. The estimated cost per screenee can be considered to be very acceptable if the current pathophysiological evidence on the potential effects of H. pylori eradication are confirmed in the future. However, there is uncertainty about the possible negative effect of eradicating H. pylori infection on gastro-esophageal reflux disease and esophageal adenocarcinoma. This could change the balance of benefits against risks of eradicating H. pylori infection.

Adolescent↗
PubMed2004

Prognostic significance of antrum-predominant gastritis in functional dyspepsia.

BACKGROUND: The role of Helicobacter pylori infection in functional dyspepsia is still controversial, and subgroups of patients with functional dyspepsia who may benefit from H. pylori eradication should be identified. Patients with functional dyspepsia and antrum-predominant H. pylori-positive chronic gastritis, it has been argued, have fewer symptoms after eradication therapy. In the present study, we analysed the clinical significance of antrum-predominant gastritis on the long-term prognosis of functional dyspepsia. METHODS: Consecutive unselected dyspeptic patients were investigated in primary care and the patients with functional dyspepsia were enrolled in this long-term follow-up study. Altogether 182 patients were recruited: 65 with normal histology of the stomach, 36 with antrum-predominant gastritis, 21 with corpus-predominant gastritis and 60 with pangastritis. Patients' medical histories were reviewed after 6 to 7 years, with total number and outcome of repeated investigations analysed. At the end of follow-up, all patients were invited for voluntary gastroscopy. RESULTS: At the end of follow-up, the proportion of asymptomatic patients ranged from 21% (normal histology) to 26% (antrum-predominant gastritis). No statistically significant differences between groups appeared in regard to re-visits or to proportion of patients examined by sigmoideo- or colonoscopy during follow-up. Patients with antrum-predominant gastritis less often underwent upper endoscopy. Peptic ulcer was more frequent (P = 0.05) in patients with antrum gastritis than in other groups, but no other differences existed among any organic gastrointestinal findings. No significant differences between subgroups appeared among the 30% of patients using drugs for upper abdominal complaints during the previous year. CONCLUSIONS: Functional dyspepsia has an excellent long-term prognosis. Antrum-predominant gastritis in functional dyspepsia seems to carry an increased risk for peptic ulcer, and for this group in particular, H. pylori eradication should be considered. This finding requires confirmation in future studies performed in primary care.

Case-Control Studies↗
PubMed2004

Does the 'test-and-treat' strategy work in primary health care for management of uninvestigated dyspepsia? A prospective two-year follow-up study of 1552 patients.

BACKGROUND: Although the 'test-and-treat' strategy is suggested as first-line therapy for uninvestigated dyspepsia, no large-scale studies in a real-life setting are available. METHODS: 1552 dyspeptic patients aged between 25 and 60 with no alarm symptoms were recruited to the study. After screening with a 13C-urea breath test, they were randomized into three treatment arms: Helicobacter pylori-positive either to eradication therapy with OAM (omeprazole, amoxycillin and metronidazole) (Hp+/erad) or omeprazole 20 mg daily (Hp+/ome) for 10 days, whereas H. pylori-negative patients (Hp-/ome) were treated with 20 mg omeprazole for 10 days. Gastrointestinal symptoms were registered at baseline at 1 and 2 years on the Gastrointestinal Symptom Rating Scale (GSRS) and quality of life with the Psychological General Well-Being index (PGWB). Additional visits, referrals for and number of endoscopies and their findings were registered during the 2 years' follow-up. RESULTS: Of the 1552 patients, 583 were H. pylori-positive (37.6%), and 288 of these were randomized for omeprazole and 295 to OAM. The Hp-/ome group had fewer general practitioner (GP) contacts (P<0.0001) than the H. pylori-positive groups. Eradication therapy significantly improved general well-being and reduced upper gastrointestinal symptoms: abdominal pain (P=0.0001), heartburn (P=0.0061), acid regurgitation (P=0.003), hunger pain (P=0.009), especially in Hp+/erad. Peptic ulcer was found in 6.2%, 1.0%, 0.2% in Hp+/ome, Hp-+/erad and Hp-/ome, respectively (P=0.0007). Only 3 patients (1.0%) developed peptic ulcers in Hp-+/erad, all eradication failures. CONCLUSIONS: In uninvestigated dyspepsia, a negative test result for H. pylori reduces the number of GP contacts and endoscopy referrals compared to H. pylori-positive regardless of eradication therapy. Applied in real life, the test-and-treat strategy failed to reduce the number of endoscopies, but significantly reduced peptic ulcer disease and improved dyspeptic symptoms and quality of life.

Adult↗
PubMed2004

CARD15 frameshift mutation in patients with CROHN disease is associated with immune dysregulation.

BACKGROUND: Mutations in the caspase-activating recruitment domain 15 (CARD15) gene are associated with Crohn disease (CD). CARD15 is an intracellular receptor for bacterial lipopolysaccharides (LPS). LPS-induced activation of transfectants containing the frameshift mutation (1007fs) of CARD15 is impaired. The aim of this study was to investigate whether the presence of CARD15 1007fs affects activation of CD patients' own cells. Patients (4 homozygotes, 6 heterozygotes, and 6 wild-type) were matched according to clinical picture and medication. METHODS: Immune inflammatory status was evaluated by measuring monocyte HLA-DR and CD11b densities and the proportion of CD14dimCD16+ monocytes, and was found to be comparable in the three groups. Blood mononuclear cells were cultured overnight in serum-free medium alone, or the medium supplemented with LPS (0.1-10.0 ng/mL), a combination of IFN-gamma (100 IU/mL) and granulocyte-macrophage colony stimulating factor (GM-CSF) (5 ng/mL), or both. TNF and IL-10 levels in the culture supernatant were determined. RESULTS: LPS 0.1 or 1.0 ng/mL alone did not increase TNF levels. IFN-gamma/GM-CSF induced TNF release, and co-culture with LPS 1.0 or 10.0 ng/mL was strongly synergistic. CARD15 1007fs mutation was linked in a gene-dose-dependent manner to low TNF release induced by IFN-gamma/GM-CSF (P value for linear trend = 0.001). The degree of synergism in co-culture was normal or high, suggesting that 1007fs did not depress responses to LPS. IL-10 levels were not related to CARD15 1007fs. CONCLUSIONS: In CD patients, CARD15 1007fs is associated in a gene-dose-dependent manner to low mononuclear cell TNF release by IFN-gamma/GM-CSF but does not impair TNF release by LPS. This type of immune dysregulation may influence susceptibility to and/or phenotype of CD.

Adult↗
PubMed2004

Factors associated with disease activity of pouchitis after surgery for ulcerative colitis.

BACKGROUND: Pouchitis occurs in 20% to 59% of patients operated on for ulcerative colitis. Several risk factors have been identified for the development of pouchitis. This study was undertaken to assess the incidence of pouchitis at least 5 years after ileal pouch-anal anastomosis for ulcerative colitis, and to evaluate possible predictive factors for inflammation activity. METHODS: A total of 107 subjects were enrolled (54 M, 53 F, mean age 45 years, range 23-69) with a J-pouch created between 1985 and 1994. Preoperative medical history was determined, an endoscopy performed, and biopsies taken from the pouch and neoterminal ileum above the pouch. Sera from all patients were tested for perinuclear antineutrophil cytoplasmic antibodies (pANCAs). RESULTS: After a mean 7.5-years' follow-up time, the cumulative incidence of pouchitis was 58%. Risk for development of active inflammation (PDAI > or = 7) was significantly higher in patients with preoperative extraintestinal manifestations (OR 2.7, 95% CI 1.1-6.4, P=0.03). Patients who had had ankylosing spondylitis (AS) (OR 11.7, P=0.006) or iritis (OR 9.8, P=0.013) were especially at risk. Positive titres of pANCAs were associated with inflammation in the neoterminal ileum; 80% of patients with high pANCA levels (>100) had pouchitis. Current smokers tended to have a more benign disease course. CONCLUSIONS: A correlation existed between the prevalence and titre of pANCAs and extent and disease activity of pouchitis. Chronic pouchitis may continuously stimulate the immunological process, keeping pANCAs at detectable levels. A strong correlation between AS, iritis and pouchitis suggests a common link in their pathogenesis.

Adult↗
PubMed2004

Immune activation in the small intestine in patients with rheumatoid arthritis.

OBJECTIVES: To determine whether inflammation in the gut associated immune system is activated in rheumatoid arthritis (RA). The expression of chemokine receptor- (CCR4, CCR5) and cytokine- (interleukin (IL)2, IL10, interferon gamma (IFNgamma), tumour necrosis factor alpha (TNFalpha), and transforming growth factor beta (TGFbeta)) specific mRNA in intestinal biopsy samples from patients with RA was examined. METHODS: Duodenal biopsy samples from 13 patients with RA and 15 control subjects were studied. The mRNA expression of CCR4, CCR5, IL2, IL10, IFNgamma, TNFalpha, and TGFbeta in intestinal biopsy samples was demonstrated by real time quantitative reverse transcriptase-polymerase chain reaction. RESULTS: The mRNA expression of CCR4, CCR5, and IL10 in intestinal biopsy samples was increased in patients with RA in comparison with control subjects (p = 0.001, p = 0.046, p = 0.019). No difference in the expression levels of IL2, IFNgamma, TNFalpha, or TGFbeta was seen between patients with RA and controls. CONCLUSIONS: The increased intestinal mRNA expression of IL10, CCR5, and CCR4 suggests that gut associated immune cells are activated in patients with RA.

Adult↗
PubMed2004

Multicentre, randomised, double blind, placebo controlled, phase III study of weekly, low dose, subcutaneous interferon beta-1a in secondary progressive multiple sclerosis.

OBJECTIVE: Interferon (IFN) beta has repeatedly shown benefit in multiple sclerosis (MS) in reducing the rate of relapse, the disease activity as shown with magnetic resonance imaging and, to some degree, the progression of disability; however, it is unknown how much the therapeutic response depends on the dose, the subgroup involved, and the disease stage. This multicentre, double blind, placebo controlled study explored the dose-response curve by examining the clinical benefit of low dose IFN beta-1a (Rebif), 22 micro g subcutaneously once weekly, in patients with secondary progressive MS. METHODS: A total of 371 patients with clinically definite SPMS were randomised to receive either placebo or subcutaneous IFN beta-1a, 22 micro g once weekly, for 3 years. Clinical assessments were performed every 6 months. The primary outcome was time to sustained disability, as defined by time to first confirmed 1.0 point increase on the Expanded Disability Status Scale (EDSS). Secondary outcomes included a sensitive disability measure and relapse rate. RESULTS: Treatment had no beneficial effect on time to confirmed progression on either the EDSS (hazard ratio (HR) = 1.13; 95% confidence interval (CI) 0.82 to 1.57; p = 0.45 for 22 micro g v placebo) or the Regional Functional Status Scale (HR = 0.93; 95% CI 0.68 to 1.28; p = 0.67). Other disability measures were also not significantly affected by treatment. Annual relapse rate was 0.27 with placebo and 0.25 with IFN (rate ratio = 0.90; 95% CI 0.64 to 1.27; p = 0.55). The drug was well tolerated with no new safety concerns identified. No significant gender differences were noted. CONCLUSIONS: This patient population was less clinically active than SPMS populations studied in other trials. Treatment with low dose, IFN beta-1a (Rebif) once weekly did not show any benefit in this study for either disability or relapse outcomes, including a subgroup with preceding relapses. These results add a point at one extreme of the dose-response spectrum of IFN beta therapy in MS, indicating that relapses in this phase may need treatment with higher doses than in the initial phases.

Adjuvants, Immunologic↗