Stable excess mortality in a multiple sclerosis cohort diagnosed 1970-2010.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is associated with excess mortality. The use of disease-modifying treatments (DMTs) has recently been associated with survival benefits. METHODS: A regional MS database was linked with national registries. People with MS (pwMS) diagnosed in 1971-2010 were included and followed up until the end of the year 2019. Five matched controls were acquired for every person with MS. DMTs included in the analyses were interferon and glatiramer acetate. RESULTS: Median follow-up time of the 1795 pwMS was 20.0 years (range 0.1-48.7 years). Survival did not differ between decades of diagnosis (p = 0.20). Amongst pwMS, male sex (adjusted hazard ratio [aHR] 1.70; 95% confidence interval [CI] 1.41-2.06), higher age at diagnosis (aHR 1.83; 95% CI 1.65-2.03 per 10-year increment) and primary progressive disease course (aHR 1.29; 95% CI 1.04-1.60) were independently associated with poorer survival. DMT use was associated with better survival (p < 0.0001) and better survival during follow-up (aHR 0.56; 95% CI 0.38-0.81). Compared to matched controls, median life expectancy was 8-9 years shorter in pwMS with survival diverging from controls during the first decade after diagnosis, more clearly in men than women. CONCLUSION: Despite DMT use being associated with better survival, relative life expectancy of pwMS did not change over five decades in Western Finland. Male sex was an independent risk factor for death amongst pwMS, but excess mortality was higher in women. More work and methods are needed to improve survival in pwMS.

The varied clinical and radiological manifestations of contrast-induced encephalopathy following coronary angiography.

Contrast-induced encephalopathy (CIE) is a rare complication of imaging using ionidated contrast media. Its pathogenesis remains unknown, and its clinical presentation is variable. We present two cases of CIE following coronary angiography (CAG) that underscore the multitude of clinical manifestations and imaging findings associated with the disorder. In patient 1, CIE manifested during the CAG with agitation and decreased consciousness, followed by left hemiparesis and visual neglect. Native computed tomography (CT) of the head was unremarkable but CT perfusion (CTP) showed extensive hypoperfusion of the right hemisphere with corresponding slow-wave activity in the electroencephalogram (EEG). These findings were more pronounced the next day. Magnetic Resonance Imaging (MRI) revealed multiple small dot-like ischemic lesions across the brain. By day 6, she had fully recovered. Patient 2 developed transient expressive aphasia during the CAG followed by migraineous symptoms. Native head CT showed a large area of parenchymal edema, sulcal effacement and variable subarachnoid hyperdensity in the right hemisphere. He developed mild left-side hemiparesis, spontaneous gaze deviation and inattention. Brain MRI showed small dot-like acute ischemic lesions across the brain. The next morning, he had a generalized tonic-clonic seizure (GTCS) after which native head CT was normal, but the EEG showed a post-ictal finding covering the right hemisphere. His hemiparesis resolved within 2 months. The diversity in clinical and radiographic presentations suggest that CIE involve many pathophysiological processes.

The incidence and management of slipped capital femoral epiphysis: a population-based study.

We aimed to investigate the national trends in the incidence and management of slipped capital femoral epiphysis (SCFE) and to report the need for reoperations. We included all <19-year-old patients hospitalised for SCFE in 2004-2014 in mainland Finland (n=159). Data from the Finnish Care Register for Health Care, Statistics Finland, and Turku University Hospital patient charts were analyse for the incidence of SCFE in 2004-2012, the length of stay, and the type of surgery with respect to age, gender, study year, and season. The reoperations and rehospitalisations in 2004-2014 for SCFE were analysed for 2-10 years after surgery. In 2004 to 2012, primary surgery for SCFE was performed for 126 children. The average annual incidence of SCFE was 1.06/100 000 (95% confidence interval [CI], 0.81-1.38) in girls and 1.35/100 000 (95% CI 1.07-1.70) in boys. The median age at surgery was lower in girls than in boys (11 and 13 years, respectively, p<0.0001). During the study period, there was no significant change in the incidence of SCFE (p=0.9330), the type of primary procedures performed (p=0.9988), or the length of stay after the primary procedure (p=0.2396). However, the length of stay after percutaneous screw fixation was shorter compared with open reduction and fixation (mean 3.4 and 7.9 days, respectively, p<0.0001). There was no significant difference in the rate of reoperations according to the type of primary surgery. In conclusion, the incidence of SCFE and the proportion of different primary surgeries have recently remained stable in Finland.

Epidemiology of stroke in Finnish patients with Huntington's disease.

OBJECTIVES: Diabetes mellitus and hypercholesterolemia are known risk factors of stroke, and altered glucose and cholesterol metabolism has been reported in patients with Huntington's disease (HD). We investigated the incidence and risk factors of stroke in this population. MATERIALS AND METHODS: National registries were used to identify a cohort of 192 patients with HD. Data on stroke, silent cerebral infarcts and risk factors were obtained from the patient records. RESULTS: Five patients with an ischemic stroke (IS) were found suggesting a crude incidence of 42/100,000 person years. Silent brain infarcts were found in 13 patients and a hemorrhagic stroke in two patients, while none were found with a transient ischemic attack (TIA). The cumulative incidence of IS was 2.7% and that of silent cerebral infarct 6.7% by age of 65 years. The CAG age product (CAP) score, an estimate of genetic burden, was 495 ± 117 for the patients with IS or silent cerebral infarct and 568 ± 126 for the patients without ischemic events (P = 0.025 for difference). The frequency of diagnoses of stroke risk factors was at least twofold higher among the patients with IS or silent infarcts than among those without. CONCLUSION: Cerebrovascular disease is as common in patients with HD as in the general population, but minor cerebrovascular events and vascular risk factors may remain unrecognized. Genetic burden of the HTT mutation does not appear to increase the risk of stroke.

The incidence and triggers of adult-onset Guillain-Barré syndrome in southwestern Finland 2004-2013.

BACKGROUND AND PURPOSE: A Swiss study recently reported surgery as a potential risk factor for developing Guillain-Barré syndrome (GBS). It was sought to establish this in the Finnish adult population. METHODS: Persons over 16 years of age who received a diagnosis of GBS in 2004-2013 were identified from the patient register of Turku University Hospital and their patient records were analyzed to identify possible triggers. RESULTS: A cohort of 69 adult patients with GBS (63.8% men) was identified giving an annual incidence of 1.82/100,000. Of these, four (5.8%) had experienced a surgical procedure during the preceding 6 weeks with a relative risk of 6.28 (95% confidence interval 4.15-9.47, P < 0.001) compared with the general study population or a risk of 1.25/100,000 operations. No difference between genders was found. Only two (2.9%) patients had received a vaccination [one against seasonal influenza (P = 0.888) and one against pandemic influenza (Pandemrix(®), GlaxoSmithKline Biologicals, Rixensart, Belgium, relative risk 2.85, 95% confidence interval 1.27-6.38, P = 0.011)] during the preceding 6 weeks. The most common GBS triggers identified were respiratory tract infections in 30 cases (43.5%) and gastroenteritis in 16 cases (23.2%) whilst two patients (2.9%) had had both. CONCLUSIONS: The overall incidence of GBS in the adult population of southwestern Finland was similar to previous studies worldwide and the most common triggers were respiratory tract infections and gastroenteritis. Surgery was a rare risk factor and of vaccinations only the one against pandemic influenza raised the risk of GBS.

Presenting symptoms of glioma in adults.

OBJECTIVE: Studies on the presenting symptoms of glioma in adults in the age of readily available MRI imaging are scarce. This study investigates presenting symptoms of glioma and assesses the correlations of the presenting symptoms with patient age and histopathological class of the tumor. MATERIALS AND METHODS: A retrospective review of the medical records of histologically verified glioma patients treated in Turku University Hospital, during 2006-2010, was conducted. The associations between the presenting symptoms and other covariates were assessed individually. RESULTS: One hundred and fifty patients were ascertained. The most common presenting symptoms of glioma were seizure and cognitive disorder. Patients presenting with seizures were younger than patients with cognitive disorders, and the grade of the tumor was also found to significantly correlate with the most common presenting symptoms. Age group and tumor grade were statistically significant factors of cognitive disorder (P = 0.0037 and P = 0.0069) and age group of seizure (P = 0.0065). The associations between the presenting symptoms and the anatomical location, spread into adjacent brain areas, or laterality of the tumor or site of diagnosis were found to be statistically insignificant. Headache was not a common presenting symptom in glioma patients. CONCLUSIONS: The main presenting symptoms of glioma in adults in the MRI age still are seizures and cognitive disorder. Patient age and tumor grade correlate positively with the incidence of cognitive disorder and patient age negatively with incidence of seizure as a presenting symptom. Headache is an uncommon manifestation and does not appear as a sole symptom.

Acoustic rhinometry, rhinomanometry and visual analogue scale before and after septal surgery: a prospective 10-year follow-up.

OBJECTIVES: The aim of the study was to compare rhinomanometry, acoustic rhinometry and subjective estimation of the nasal obstruction before and after septoplasty and to evaluate the long-term results of septal surgery. DESIGN: Prospective long-term follow-up, before and after septoplasty. SETTING: University tertiary-care hospital, referral centre. PARTICIPANTS: The study included 30 adult patients who were operated on because of septal deviation. MAIN OUTCOME MEASURES: Pre-operatively, acoustic rhinometry and active anterior rhinomanometry were performed on each subject after decongestion of the nose. A visual analogue scale for unilateral nasal obstruction was filled in by the patients. The measurements were repeated both 6 months and 10 years post-operatively. RESULTS: A significant change in acoustic values was found during the long-term follow-up of 10 years. The mean minimal cross-sectional area on the more obstructive side was 0.35 cm(2) pre-operatively. Six months after operation, it was 0.52 cm(2), and 10 years after operation, it was 0.68 cm(2). The mean resistance fell from pre-operative 1.16 Pa/mL/s to 0.41 Pa/mL/s during the first 6 months, but rose again to 1.21 Pa/mL/s after 10 years. Despite a tendency of improvement, no statistically significant change was found between pre-operative and postoperative values in VAS. Six months after operation 69% of the patients were satisfied with the result, and after ten years the amount of satisfied patients was 83%. CONCLUSIONS: We found an increase in acoustic values, but an increase in nasal resistance in the long-term follow-up. Other factors than nasal area may have an impact on nasal resistance and the feeling of nasal obstruction. The small size on the sample interfered with the results.

Reference values for acoustic rhinometry in children at baseline and after decongestion.

BACKGROUND: Acoustic rhinometry is widely used for objective evaluation of nasal dimensions. However, there is a lack of agreement on the normative values in children at baseline, and especially after decongestion. The purpose of this study was to determine the reference values for Finnish school children for acoustic rhinometry in non-decongested and decongested noses, and to find out which of the potential predictors (age, sex, body surface area (BSA) and height) would be the most useful one(s). METHODOLOGY: The study included 124 children aged between 6.90 and 13.84 years with no permanent nasal symptoms. RESULTS: At baseline, the mean total minimal cross-sectional area (MCA) was 0.752 cm2, and the mean total volume between 0 - 3 cm (VOL) was 4.00 cm3. After decongestion, the total MCA was 0.794 cm2, and the VOL was 4.38 cm3. There was a significant correlation between MCA and age, between VOL and height, and between VOL and BSA at baseline and after decongestion. We found no difference in the values between boys and girls. CONCLUSIONS: We conclude that acoustic rhinometry is a suitable objective method to monitor the changes in mucosal swelling and nasal obstruction in children. Age and height or BSA of a child can be suggested as predictive factors.

Correlation between acoustic rhinometry and visual analogue scale in children with no nasal symptoms: a prospective cohort study.

OBJECTIVES: Acoustic rhinometry is an objective tool to evaluate nasal obstruction. The aim of this study was to evaluate the usefulness of visual analogue scale (VAS) as a subjective tool for nasal obstruction and the correlation between acoustic rhinometry and VAS in children with no nasal symptoms. DESIGN: Unilateral acoustic values and VAS were measured at baseline and after decongestion of the nose. SETTING: Tertiary academic hospital. PARTICIPANTS: The study included 124 children aged between 7 and 14 years with no permanent nasal symptoms. RESULTS: At baseline, the mean minimal cross-sectional area on the right side was 0.392 cm(2) (sd 0.094), and on the left side 0.360 cm(2) (sd 0.093), whereas the mean VAS on the right side was 7.43 (sd 2.50) and on the left side 6.81 (sd 3.01). After decongestion, the mean minimal cross-sectional area on the right and left sides were 0.421 cm(2) (sd 0.087) and 0.373 cm(2) (sd 0.11), respectively, whereas the mean VAS on the right and left sides were 8.77 (sd 2.02) and 8.54 (sd 2.14), respectively. At baseline, a significant correlation was found between VAS and minimal cross-sectional area, but no correlation was found between VAS and acoustic values after decongestion. CONCLUSIONS: We conclude that VAS shows potential as a subjective tool to investigate nasal obstruction in children over 7 years of age. There was a correlation between VAS and acoustic rhinometry in children with no nasal symptoms at baseline. No correlation was found in children with decongested normal nasal airways.

High redox potential laccases from the ligninolytic fungi Pycnoporus coccineus and Pycnoporus sanguineus suitable for white biotechnology: from gene cloning to enzyme characterization and applications.

AIMS: Exploitation of natural biodiversity in species Pycnoporus coccineus and Pycnoporus sanguineus to screen for a new generation of laccases with properties suitable for the lignin-processing sector. METHODS AND RESULTS: Thirty strains originating from subtropical and tropical environments, mainly isolated from fresh specimens collected in situ, were screened for laccase activity. On the basis of levels of enzyme activity and percentage of similarity between protein sequences, the laccases from strains BRFM 938, BRFM 66 and BRFM 902 were selected for purification and characterization. Each BRFM 938, BRFM 66 and BRFM 902 laccase gene encoded a predicted protein of 518 amino acids; the three deduced proteins showed 68.7-97.5% similarity with other Polyporale laccases. The three laccases (59.5-62.9 kDa with 7-10% carbohydrate content) had high redox potentials (0.72-0.75 V vs normal hydrogen electrode at pH 6), remained highly stable up to 75-78 degrees C and at pH 5-7 mixtures, and were resistant to methyl and ethyl alcohols, acetonitrile and dimethylsulfoxide at concentrations as high as 50% (v/v). The best laccase-1-hydroxybenzotriazole systems permitted almost 100% of various polyphenolic dye decolourization and oxidation of adlerol and veratryl alcohol. CONCLUSIONS: The three laccases showed complementary biochemical features. BRFM 938 laccase had the highest thermo- and pH stability, catalytic efficiency towards 2,2'-azino-bis-[3-ethylthiazoline-6-sulfonate] and resistance to alcoholic solvents. BRFM 66 laccase had the highest rates of dye decolourization and oxidation of nonphenolic compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study identified P. coccineus and P. sanguineus as outstanding producers of high redox potential laccases, easy to purify and scale-up for industrial production. Three new laccases proved to be suitable models for white biotechnology processes and for further molecular breeding to create a new generation of tailor-made enzymes.

beta-fluoro-coniferyl alcohol does not inhibit lignin biosynthesis in suspension cultures of Picea abies (L.) Karst.

A fluorinated analogue of coniferyl alcohol has been reported to be a specific inhibitor of oxidases involved in the biosynthesis of lignin. The Z isomer of beta-fluoro-coniferyl alcohol was synthesized and used for the preparation of dehydrogenation polymers (DHPs) and was also tested on lignin producing suspension cultures of spruce (Picea abies (L.) Karst.). The growth of the cells or the production of lignin by the suspension cultures was not significantly affected by the addition of fluoroconiferyl alcohol. This analogue did not form polymers quite as easily as did coniferyl alcohol in oxidation with hydrogen peroxide and horseradish peroxidase. In both cases the beta-fluoroconiferyl alcohol became incorporated in the polymeric product. We were unable to detect any specific inhibition of peroxidase activity, which is at variance with earlier reports of pronounced inhibition of lignin biosynthesis in poplar plantlets by fluoroconiferin, a potential inhibitor of oxidases involved in lignin biosynthesis.

Prediction of the clinical outcome of acute frontal sinusitis with ventilation measurement of the nasofrontal duct after trephination: a long-term follow-up study.

Acute frontal sinusitis has become an increasing clinical problem in the region that is served by the hospital represented by the authors of this study. The standard surgical treatment protocol after the failure of conservative therapy has been to perform trephination of the involved frontal sinus. More sophisticated procedures have been used in patients with prolonged or recurrent disease. The authors have developed a simple ventilation test of the nasofrontal duct that can be used to determine which patients require further surgery. In a long-term follow-up study of 85 patients, this ventilation test was shown to predict the cases that would heal uneventfully after trephination and the cases that would require further surgery because of an obstructed nasofrontal duct. The findings of this study are of special interest for modern functional endoscopic sinus surgery, the purpose of which is to open up the nasofrontal region.

The identification of dilignols from dehydrogenation mixtures of coniferyl alcohol and apocynol [4-(1-Hydroxyethyl)-2-methoxyphenol] by LC-ES-MS/MS.

A LC-ES-MS/MS method for the identification of dilignols formed by the oxidative cross-coupling of coniferyl alcohol and apocynol has been developed. The identification is based on the generation of ammonium adduct ions [M + NH(4)](+) by electrospray ionization and thereafter the following fragmentation patterns for the selected precursor ions. Fragmentation of several arylglycerol-beta-aryl ether (beta-O-4) and phenyl coumarane (beta-5) model compounds were studied as a reference.

Group II phospholipase A2 in nasal fluid, mucosa and paranasal sinuses.

The aim of this study was to determine the type of phospholipase A2 (PLA2) in nasal fluid and to demonstrate its cellular origin. The concentration of group II PLA2 was high (591.5 micrograms/l) in nasal fluid compared with serum level (10.8 micrograms/l) and the fluid of paranasal sinuses (10.6 micrograms/l). Methacholine stimulated nasal fluid contained only small amounts (19.1 micrograms/l) of group II PLA2 when the flow of tear fluid through the nasolacrimal duct was obstructed. Occasional glands secreting group II PLA2 were found in nasal and paranasal mucosa by immunohistochemistry. Lysozyme was found in the majority of mucosal glands. It was concluded that nasal and paranasal mucosal glands contain group II PLA2. In nasal fluid, however, PLA2 is mainly derived from tear fluid.

The effect of flunitrazepam on acoustic reflex--a methodological pilot study.

Four healthy volunteers took part in this study in four sessions at one week intervals minimum. Three intravenous dose levels of flunitrazepam as well as placebo (saline) were investigated. The sessions were randomized and the study was double blind. The results show that a significant correlation exists between the serum concentrations of flunitrazepam and acoustic reflex amplitude, latency, Maddox wing readings and subjective sedation. Critical flicker fusion frequency test was insensitive in this respect. We conclude that acoustic reflex may be a new method for determination of benzodiazepine effects in man.

Patency of nasofrontal duct during the healing process of trephined acute frontal sinusitis. A clinical application of modern rhinomanometry.

Thirty-one patients suffering from acute frontal sinusitis were treated by trephination. The patency of the nasofrontal duct was measured daily via the ventilation tube by computerized rhinomanometry until the tube was removed. According to the air flow changes inside the frontal sinus during normal nasal breathing, the duct was assessed as open, partially open or obstructed. The further healing process was assessed by clinical and radiological examination during a two-month postoperative follow-up. Statistical analysis of the results shows that both the favourable healing process and recurrences can be predicted with this method to a very high level of significance. The method is simple and rapid and it helps to determine the correct time for the withdrawal of the irrigation tube in individual patients.

The value of computerised rhinomanometry and a simple manometry with saline in predicting the outcome of patients with acute trephined frontal sinusitis.

Infection of the anterior ethmoids and recessus frontalis causes swelling of the mucosa and obstruction of the nasofrontal duct, impairing the drainage of the frontal sinus. During the healing process the obstruction diminishes gradually. Prolongation of this process can lead to chronic infection of the nasofrontal region causing recurrent or chronic frontal sinusitis. In our everyday work we need a simple and reliable method to evaluate the patency of the nasofrontal duct, in order to be able to assess the recovery and to find those patients whose disease tends to become chronic. For this purpose we have measured the patency of the nasofrontal duct in 58 patients with frontal sinusitis after trephination with computerized rhinomanometry (RM) and with a simple salinemanometry (SM). The validity of the two methods to predict the further outcome of the patients has been compared in order to find out if SM would prove to be at least almost as reliable as rhinomanometry. Our statistics prove that SM is a useful aid in assessing the short-term recovery process of the patients. The long-term predictive value still remains to be seen.

Sensation of nasal obstruction compared to rhinomanometric results in patients referred for septoplasty.

In previous studies concerning correlations between subjective nasal obstruction and rhinomanometric findings the subjects quite often had normal nasal status and symptomless nasal breathing. The correlation sometimes proved to be poor. In the present study, intercorrelations between rhinomanometry and subjective sensation of nasal patency were evaluated in 102 patients referred for septoplasty. The hypothesis was that this material should give more realistic results than normal cases. In pre-operative rhinomanometry it was found that in 62 cases the nasal airway resistance (NAR) after decongestion of the nasal mucosa was pathological compared to our normal material and in 40 cases it was within normal range. The patients were asked, before rhinomanometric recording, to indicate the narrower side of the nose, right or left. After that, both baseline and post-decongestion recordings were made. The rhinomanometric results concerning the side difference were compared to the subjective assessment. Our results showed that in the 62 cases with pathological NAR the subjective and rhinomanometric evaluation was consistent in 46 of the baseline and 50 of the decongestion cases. In the 40 patients with normal NAR the figures were 19 and 20, respectively. It is obvious that if NAR is low it is more difficult for the patient to determine the more obstructed side. We conclude that rhinomanometry rather than the subjective sensation of the subject is more suited to detect subtle side difference in resistance between the nares.

Some fundamental studies on clinical measurement conditions in acoustic rhinometry.

Acoustic rhinometry is a new method to measure the patency of the nasal airway. In this study the clinical measuring conditions were systematically evaluated. The test-retest validity was analysed by repeated measurements in ordinary, not specially trained patients and was found to be at the level of approximately 15%. The need for acclimatization before measurements was tested by making a series of measurements on two separate occasions: one after a rest period following the patient's arrival at the nose laboratory, and a second in another session where no rest was allowed for. Statistically, no significant differences between the repeated measurements in the two occasions were found. However, there was a tendency towards smaller nasal volumes in the measures of the repeated recordings made without an acclimatization period. Therefore, it seems to be advisable to have an acclimatization period before acoustic rhinometry measurements.