Increasing incidence of bullous pemphigoid in Northern Finland: a retrospective database study in Oulu University Hospital.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering skin disease of elderly people. Some studies have suggested that the incidence of BP has increased, but the diagnostic accuracy and methodology of studies have varied considerably. OBJECTIVES: To examine the incidence of BP in Northern Finland, and whether the incidence has changed over time. METHODS: This was a retrospective database study of all BP cases diagnosed in the Oulu University Hospital, Finland between 1985 and 2009. The diagnostic criteria were clinical features characteristic of BP (all patients) and positive direct or indirect immunofluorescence in the skin biopsy. The age-standardized incidences were calculated by the direct standardization method. Incidence rate ratios (IRR) were estimated by the Poisson regression model. To derive adjusted IRRs, age and sex were used as potential confounding factors. RESULTS: The crude incidence of BP was 17 per 1 million person-years [95% confidence interval (CI) 15-20] between 1985 and 2009. Using the general European population as a reference, the age-standardized incidence was 14 per 1 million person-years (95% CI 12-17). The incidence of BP increased 1·8-fold (IRR 1·8, 95% CI 1·3-2·6; P < 0·001) in 2005-09 compared with the mean incidence of BP between 1985 and 2004, but after the adjustment for age and sex the increase was 1·4-fold (IRR 1·4, 95% CI 1·0-2·0; P = 0·043). CONCLUSIONS: This is the first study with immunohistologically verified BP diagnoses that reports the increase in the incidence of BP in age- and sex-adjusted populations.

Ultrasonic evaluation of acute impact injury of articular cartilage in vitro.

OBJECTIVE: The aim of the study was to investigate whether high frequency ultrasound technique, originally designed for arthroscopic use can be utilized to detect traumatic cartilage injuries. METHODS: A total of four intact osteochondral plugs were prepared from eight patellas for parallel comparison (total of 32 plugs). The plugs were injured by dropping an impactor on them from heights of 2.5 cm, 5.0 cm, 10.0 cm and 15.0 cm (corresponding to impact energies of 0.12, 0.25 0.50 and 0.74 J, respectively), in a custom made dropping tower. The samples were imaged with a high frequency (40 MHz) ultrasound device before and after the injury. Reflection coefficient (R), integrated reflection coefficient (IRC), apparent integrated backscattering (AIB) and ultrasound roughness index (URI) were determined for each sample. RESULTS: Injuries invisible to the naked eye could be sensitively detected via the decreased values of the ultrasound reflection parameters (P < 0.05). Furthermore, a decreasing trend was detected in the values of R and IRC as the momentum of the impactor increased. The values of AIB were significantly lower for samples injured by dropping the impactor on the cartilage from heights of 2.5 cm and 15 cm but the URI values were similar in intact and injured cartilage. Histological analysis of the cartilage samples revealed that the injured cartilage exhibited depletion of the cartilage surface proteoglycans but the structure of collagen network was almost normal. CONCLUSIONS: Quantitative ultrasound imaging enables the detection of minor visually non-detectable cartilage injuries. As the present technique is feasible for arthroscopic use it might have clinical value in the evaluation of cartilage lesions during arthroscopy e.g., after tear of the anterior cruciate ligament.

MD dating: molecular decay (MD) in pinewood as a dating method.

Dating of wood is a major task in historical research, archaeology and paleoclimatology. Currently, the most important dating techniques are dendrochronology and radiocarbon dating. Our approach is based on molecular decay over time under specific preservation conditions. In the models presented here, construction wood, cold soft waterlogged wood and wood from living trees are combined. Under these conditions, molecular decay as a usable clock for dating purposes takes place with comparable speed. Preservation conditions apart from those presented here are not covered by the model and cannot currently be dated with this method. For example, samples preserved in a clay matrix seem not to fit into the model. Other restrictions are discussed in the paper. One model presented covers 7,500 years with a root mean square error (RMSE) of 682 years for a single measurement. Another model reduced to the time period of the last 800 years results in a RMSE of 92 years. As multiple measurements can be performed on a single object, the total error for the whole object will be even lower.

Hyperglycaemia is associated with changes in the regional concentrations of glucose and myo-inositol within the brain.

AIMS/HYPOTHESIS: The aim of the study was to assess the effect of hyperglycaemia on regional concentrations of glucose and other substrates within the brain in non-diabetic individuals and in patients with type 1 diabetes. METHODS: The brain metabolites of 17 men with type 1 diabetes and 12 age-matched non-diabetic men (22-43 years old) were studied after an overnight fast (plasma glucose 9.2 +/- 3.0 vs 4.8 +/- 0.5 mmol/l, respectively). N-Acetylaspartate (NAA), creatine, choline, myo-inositol (mI) and glucose in the frontal cortex, frontal white matter and thalamus were quantified with proton magnetic resonance spectroscopy. RESULTS: In the non-diabetic participants, the glucose level was 47% higher (p < 0.01) in the frontal cortex than in the frontal white matter. In contrast, this regional variation was not observed in the diabetic participants, in whom the glucose level in the frontal white matter was 64% higher (p < 0.001) and in the frontal cortex 25% higher (p = 0.033) than that of the non-diabetic participants. In the diabetic participants, the glucose level in each of the three regions studied correlated with fasting plasma glucose (r = 0.88-0.67, p < 0.01). In addition, in the diabetic participants, mI was 20% higher (p < 0.001) and NAA 6% lower (p = 0.037) in the frontal white matter, and mI was 8% higher (p = 0.042) in the frontal cortex, than in the non-diabetic participants. CONCLUSIONS/INTERPRETATION: In type 1 diabetes, hyperglycaemia is associated with accumulation of glucose and mI in the cortex and in the white matter.

Tree height strongly affects estimates of water-use efficiency responses to climate and CO2 using isotopes.

Various studies report substantial increases in intrinsic water-use efficiency (W i ), estimated using carbon isotopes in tree rings, suggesting trees are gaining increasingly more carbon per unit water lost due to increases in atmospheric CO2. Usually, reconstructions do not, however, correct for the effect of intrinsic developmental changes in W i as trees grow larger. Here we show, by comparing W i across varying tree sizes at one CO2 level, that ignoring such developmental effects can severely affect inferences of trees' W i . W i doubled or even tripled over a trees' lifespan in three broadleaf species due to changes in tree height and light availability alone, and there are also weak trends for Pine trees. Developmental trends in broadleaf species are as large as the trends previously assigned to CO2 and climate. Credible future tree ring isotope studies require explicit accounting for species-specific developmental effects before CO2 and climate effects are inferred.Intrinsic water-use efficiency (W i ) reconstructions using tree rings often disregard developmental changes in W i as trees age. Here, the authors compare W i across varying tree sizes at a fixed CO2 level and show that ignoring developmental changes impacts conclusions on trees' W i responses to CO2 or climate.

1H MRS studies in the Finnish boron neutron capture therapy project: detection of 10B-carrier, L-p-boronophenylalanine-fructose.

This article summarizes the current status of 1H MRS in detecting and quantifying a boron neutron capture therapy (BNCT) boron carrier, L-p-boronophenylalanine-fructose (BPA-F) in vivo in the Finnish BNCT project. The applicability of 1H MRS to detect BPA-F is evaluated and discussed in a typical situation with a blood containing resection cavity within the gross tumour volume (GTV). 1H MRS is not an ideal method to study BPA concentration in GTV with blood in recent resection cavity. For an optimal identification of BPA signals in the in vivo 1H MR spectrum, both pre- and post-infusion 1H MRS should be performed. The post-infusion spectroscopy studies should be scheduled either prior to or, less optimally, immediately after the BNCT. The pre-BNCT MRS is necessary in order to utilise the MRS results in the actual dose planning.

Conformance of mean glandular dose from phantom and patient data in mammography.

In mammography dosimetry, phantoms are often used to represent breast tissue. The conformance of phantom- and patient-based mean glandular dose (MGD) estimates was evaluated mainly from the aspect of diagnostic reference levels. Patient and phantom exposure data were collected for eight diagnostic and three screening mammography devices. More extensive assessments were performed for two devices. The average breast thickness was close to the nationally used reference of 50 mm in diagnostic (50 mm, SD = 13 mm, n = 5342) and screening (47 mm, SD = 13 mm, n = 395) examinations. The average MGD for all breasts differed by 2% from the MGD determined for breasts in the limited compressed thickness range of 40-60 mm. The difference between phantom- and patient-based MGD estimations was up to 30%. Therefore, phantom measurements cannot replace patient dose data in MGD determination.

1H MRS of a boron neutron capture therapy 10B-carrier, L-p-boronophenylalanine-fructose complex, BPA-F: phantom studies at 1.5 and 3.0 T.

The quantification of a BNCT 10B-carrier, L-p-boronophenylalanine-fructose complex (BPA-F), was evaluated using 1H magnetic resonance spectroscopy (1H MRS) with phantoms at 1.5 and 3.0 T. For proper quantification, relaxation times T1 and T2 are needed. While T1 is relatively easy to determine, the determination of T2 of a coupled spin system of aromatic protons of BPA is not straightforward with standard MRS sequences. In addition, an uncoupled concentration reference for aromatic protons of BPA must be used with caution. In order to determine T2, the response of an aromatic proton spin system to the MRS sequence PRESS with various echo times was calculated and the product of the response curve with exponential decay was fitted to the measured intensities. Furthermore, the response curve can be used to correct the intensities, when an uncoupled resonance is used as a concentration reference. BPA was quantified using both phantom replacement and internal water referencing methods with accuracies of +/- 5% and +/- 15%. Our phantom results suggest that in vivo studies on BPA concentration determination will be feasible.

Subchronic oral toxicity study with regular and enzymatically depolymerized sodium carboxymethylcellulose in rats.

Enzymatically depolymerized sodium carboxymethylcellulose (CMC-ENZ) is a new functional food ingredient which has a lower molecular weight and viscosity than regular sodium carboxymethylcellulose (CMC). Both compounds are known not to be absorbed to a significant extent, and the human safety of CMC as a thickening agent and stabilizer in food is well established. In the present study, the subchronic oral toxicity of CMC-ENZ was examined and compared with that of CMC in Wistar rats. Seven groups of 20 rats/sex were fed diets with 0 (controls), 2.5, 5 and 10% CMC and 2.5, 5 and 10% CMC-ENZ for a 3-month period. There was only one death that was unrelated to the treatment. Water intake, urine production and urinary sodium excretion increased with increasing doses of CMC and CMC-ENZ due to their sodium content of about 7-8%. The treatment-related occurrence of diarrhoea and caecal enlargement in the mid- and high-dose groups, a slight increase of plasma alkaline phosphatase, and increased urinary calcium and citrate excretions were considered to be generic effects that typically are observed in rodent studies with low digestible carbohydrates. The increased occurrence of nephrocalcinosis and hyperplasia of the urothelial epithelium in some of the treated groups was interpreted as an indirect consequence of a more alkaline urine coupled with an increased calcium excretion. As the frequency and severity of all these changes did not differ between corresponding CMC and CMC-ENZ dose groups, it is concluded that the two products have a similar toxicological profile.

Metabolic disposition in rats of regular and enzymatically depolymerized sodium carboxymethylcellulose.

Partially enzyme-hydrolysed sodium carboxymethylcellulose (CMC-ENZ), which holds promise as a new, functional food ingredient, is obtained from sodium carboxymethylcellulose (CMC) by enzymatic hydrolysis with a cellulase preparation from Trichoderma longibrachiatum. In the safety evaluation of CMC-ENZ, a comparative disposition study on 14C-labelled CMC and CMC-ENZ was conducted in conventionally kept rats. The 14C label was in the two C atoms of the carboxymethyl group. Two groups of four male and four female rats each were fed diets with 5% unlabelled CMC or CMC-ENZ for a 2-wk adaptation period. A single oral dose of 14C-CMC or 14C-CMC-ENZ solution was then given by gavage (500 mg/kg body weight). Respiratory CO2, urine and faeces were collected at regular intervals, and after 120 hr organs, tissues and the carcass were sampled as well. For both experimental groups, total mean recovery of 14C was 98%, about 95% of the label being excreted with the faeces, 2% or less in the urine, 1% or less with CO2 and a small fraction being retained in the body (CMC, 0.58%; CMC-ENZ, 0.75%). Tissue retention of 14C was highest in the liver of rats of both experimental groups. Only about 49 and 65% of the faecal 14C was extracted with water in the 14C-CMC and 14C-CMC-ENZ dosed rats, respectively. Gel permeation chromatography (GPC) of the dosing solutions and the faecal extracts revealed that CMC is depolymerized during intestinal passage whereas CMC-ENZ is excreted nearly unchanged. Consequently, the molecular weight distribution of the 14C-CMC and 14C-CMC-ENZ faecal excretion products was similar. It is concluded that there is no toxicologically relevant difference between the disposition of CMC and CMC-ENZ.

Risk factors affecting the occurrence of acute otitis media among 2-3-year-old urban children.

The factors affecting the occurrence and recurrence of acute otitis media (AOM) were studied among 471 2-3-year-old children in two cities in Finland. Of these children, 188 had experienced greater than or equal to 3 attacks of AOM, 76 had had 1-2 attacks and 207 no otitis attacks (= control group). The study showed that the risk of recurrent AOM was increased among those children attending day-care nurseries as well as among those who had several siblings. Proneness to rhinorrhea and exposure to passive smoking at home was associated with an increased risk of AOM, while prolonged breast-feeding (greater than 6 months) seemed to reduce it. No correlation was found between the risk of recurrent AOM and the place of residence or type of housing, the parental otitis history, or atopic diathesis of a child. Thus the study suggested that to protect a young child from AOM we should promote breast-feeding and home-care for babies as well as avoid smoking in the home.

The Bayesian approach to the evaluation of risk factors in acute and recurrent acute otitis media.

A multivariant modelling method was used to analyse the risk, associated with 22 different factors, of contracting acute otitis media (AOM) in a prospective cohort of 1294 urban children followed up to the age of 17-32 (mean 25) months. By far the most important risk factor was the caring of the child at a day-care centre. The importance of this factor further increased with increasing recurrence of the attacks. Next in order came the existence of sibling(s) with AOM attacks during the follow-up. Prolongation of breastfeeding increased the protection against AOM during the first year of life. The frequency of AOM attacks was lowest around midsummer and highest in early winter.

Incidence of acute otitis media.

The occurrence of acute otitis media was studied over a one-year period in a total population of 146822 persons living in different parts of Finland. Of these 146822 persons, 4583 experienced a total of 6518 otitis attacks giving an annual incidence rate of 4.44% (4.48% in males and 4.07% in females, P less than 0.001). Acute otitis media was strikingly concentrated in the youngest age groups, with the highest annual incidence rates, in the order of 50%, found in infants younger than 2 years. Half of all the episodes occurred before the age of 33 months. The relative risk of getting acute otitis media was about 200 times higher during the first 2 years of life than as an adult. The occurrence of otitic episodes followed seasonal variations, and in urban areas the incidence was significantly (P less than 0.001) higher than in the countryside.

Branhamella catarrhalis in acute otitis media.

A total of 5217 middle ear fluid (MEF) samples obtained from 1203 children with otitis media, aged 3 months to 6 years, were studied for the presence of Branhamella catarrhalis (Br) between Oct. 1977 and Sept. 1981. Br grew in 10.2% of 3497 MEFs of acute otitis media (AOM), with almost the same frequency in the very first and subsequent attacks. During the first 4 years of life the percentage did not vary much; among older children it seemed to decrease. The overall prevalence of Br in AOM did not change during the study period. Br alone grew in 72.4% of acute MEFs with Br; with other bacteria the respective figure was 82.9% (p less than 0.001). Acute attacks with bilateral Br were found in 22.8% of attacks with Br. In 1720 non-acute MEFs obtained at postacute control visits, Br was isolated in only 7.0%. The proportion of beta-lactamase-producing strains among the 2419 otitis-Br strains tested in two laboratories of the two study regions showed an increase from 27.1% and 21.1% in 1980 to 57.6% and 38.6% in 1983, respectively (p less than 0.001).

Efficacy of pneumococcal vaccination against recurrent otitis media. Preliminary results of a field trial in Finland.

For this study, 781 children, and 3 to 83 months, after presenting with acute otitis media, were immunized with either 14-valent pneumococcal or Haemophilus influenzae type b capsular polysaccharide vaccine. The vaccines were tolerated well. Antibody responses to the 14 pneumococcal polysaccharide types, measured by radioimmunoassay, were fair to good and increased with age, with the exception of types 1, 6 and 12 to which the responses were generally poor. During the follow-up of 1-17 months, average 13 months, 45 vaccine type (except type 6) pneumococcal recurrences were met among 456 pneumococcal-vaccinated and 45 among 288 H. influenzae-vaccinated children, at least six months old (P < .05). The corresponding protective efficacy by the pneumococcal vaccine was 37%, for the first six months, 51% (P < .01). No protection by the pneumococcal vaccine was seen against group 6 pneumococci, nor among 19 infants under six months of age. Nonvaccine type pneumococcal ad H. influenzae recurrences did not significantly concentrate in either of the vaccination groups. Thus, it seems that parenteral immunization of children can reduce the recurrence rate of otitis media caused by pneumococci of types (except type 6) present in the vaccine.

Arthroscopic optical coherence tomography provides detailed information on articular cartilage lesions in horses.

Arthroscopy enables direct inspection of the articular surface, but provides no information on deeper cartilage layers. Optical coherence tomography (OCT), based on measurement of reflection and backscattering of light, is a diagnostic technique used in cardiovascular surgery and ophthalmology. It provides cross-sectional images at resolutions comparable to that of low-power microscopy. The aim of this study was to determine if OCT is feasible for advanced clinical assessment of lesions in equine articular cartilage during diagnostic arthroscopy. Diagnostic arthroscopy of 36 metacarpophalangeal joints was carried out ex vivo. Of these, 18 joints with varying degrees of cartilage damage were selected, wherein OCT arthroscopy was conducted using an OCT catheter (diameter 0.9 mm) inserted through standard instrument portals. Five sites of interest, occasionally supplemented with other locations where defects were encountered, were arthroscopically graded according to the International Cartilage Repair Society (ICRS) classification system. The same sites were evaluated qualitatively (ICRS classification and morphological description of the lesions) and quantitatively (measurement of cartilage thickness) on OCT images. OCT provided high resolution images of cartilage enabling determination of cartilage thickness. Comparing ICRS grades determined by both arthroscopy and OCT revealed poor agreement. Furthermore, OCT visualised a spectrum of lesions, including cavitation, fibrillation, superficial and deep clefts, erosion, ulceration and fragmentation. In addition, with OCT the arthroscopically inaccessible area between the dorsal MC3 and P1 was reachable in some cases. Arthroscopically-guided OCT provided more detailed and quantitative information on the morphology of articular cartilage lesions than conventional arthroscopy. OCT could therefore improve the diagnostic value of arthroscopy in equine orthopaedic surgery.

The association between anxiety and C-reactive protein (CRP) levels: results from the Northern Finland 1966 birth cohort study.

BACKGROUND: Anxiety frequently accompanies low-grade inflammation-associated conditions like depression, insulin resistance, coronary heart disease and metabolic syndrome. The association between anxiety and low-grade inflammation is, unlike between depression and low-grade inflammation, a very sparsely studied area in general populations. The aim of the present study was to investigate whether anxiety symptoms as well as comorbid anxiety and depressive symptoms are associated with low-grade inflammation at population level. METHODS: The general population-based Northern Finland 1966 Birth Cohort was followed until age 31 (n=2688 males and 2837 females), when the highly sensitive CRP concentrations were measured. Anxiety and depressive symptoms were defined by Hopkins Symptom Checklist-25 (HSCL-25). RESULTS: After adjusting for confounders, logistic regression analyses showed that anxiety symptoms alone increased the probability for elevated hs-CRP levels (>3.0mg/L) in males over two-fold (2.19 CI 95% 1.08-4.46), while comorbid anxiety and depressive symptoms caused a 1.7-fold (1.76 CI 95% 1.13-2.74) increase in the probability for elevated hs-CRP levels (1.0-3.0mg/L). CONCLUSIONS: Our results support the hypothesis that anxiety as well as comorbid anxiety and depression can be associated with an increased risk for low-grade inflammation in males at population level.

Technical and practical improvements in arthroscopic indentation technique for diagnostics of articular cartilage softening.

Indentation measurements have been proposed to serve as sensitive in vivo diagnostics of cartilage degeneration. However, practical difficulties have hindered the use of quantitative indentation techniques during routine arthroscopies. In this study we modified the previously commercial indentation technique by designing software for quality control of manual indentations. With the modifications, our aim was to introduce more rapid and less erroneous measurements, as well as more automatic and objective analyses. The performance of the technique was tested in situ using six bovine medial tibial plateaus. All measurements were conducted by three operators. The intraoperator reproducibility was reasonable (CV%  = 7.1%) and the interoperator reproducibility was good (intraclass correlation coefficient  = 0.976). Further, the novel technique was tested by a single operator using 10 bovine medial tibial plateaus. The indentation stiffness values determined with the arthroscopic instrument correlated significantly with the dynamic (r = 0.823) and equilibrium (r = 0.752) moduli as well as tissue water (r =  -0.830) and hydroxyproline (r = 0.776) contents. To conclude, the novel measurement technique showed good reproducibility and was found to give valuable information on cartilage properties. Most importantly, the measurements and analyses were more straightforward and automatic than those introduced in the original indentation approach.