The validity of rheumatoid arthritis diagnoses in Finnish biobanks.

OBJECTIVE: The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks. METHOD: We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients' diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland. RESULTS: The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98. CONCLUSION: These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data.

Hereditary palmoplantar keratoderma - phenotypes and mutations in 64 patients.

BACKGROUND: Hereditary palmoplantar keratodermas (PPK) represent a heterogeneous group of rare skin disorders with epidermal hyperkeratosis of the palms and soles, with occasional additional manifestations in other tissues. Mutations in at least 69 genes have been implicated in PPK, but further novel candidate genes and mutations are still to be found. OBJECTIVES: To identify mutations underlying PPK in a cohort of 64 patients. METHODS: DNA of 48 patients was analysed on a custom-designed in-house panel for 35 PPK genes, and 16 patients were investigated by a diagnostic genetic laboratory either by whole-exome sequencing, gene panels or targeted single-gene sequencing. RESULTS: Of the 64 PPK patients, 32 had diffuse (50%), 19 focal (30%) and 13 punctate (20%) PPK. None had striate PPK. Pathogenic mutations in altogether five genes were identified in 31 of 64 (48%) patients, the majority (22/31) with diffuse PPK. Of them, 11 had a mutation in AQP5, five in SERPINB7, four in KRT9 and two in SLURP1. AAGAB mutations were found in nine punctate PPK patients. New mutations were identified in KRT9 and AAGAB. No pathogenic mutations were detected in focal PPK. Variants of uncertain significance (VUS) in PPK-associated and other genes were observed in 21 patients that might explain their PPK. No suggestive pathogenic variants were found for 12 patients. CONCLUSIONS: Diffuse PPK was the most common (50%) and striate PPK was not observed. We identified pathogenic mutations in 48% of our PPK patients, mainly in five genes: AQP5, AAGAB, KRT9, SERPINB7 and SLURP1.

Bacterial skin flora and contamination of blood components: do we defer blood donors wisely?

BACKGROUND AND OBJECTIVES: Bacterial infection through contaminated blood is currently the greatest infection risk in relation to a transfusion. Deferral of prospective blood donors with a skin disorder is a common practise, because bacteria usually originate from the donor's skin. The effectiveness of current deferral guidelines to prevent the bacterial contamination of blood has not been assessed. MATERIALS AND METHODS: We recruited 55 blood donors with a skin disorder that prevented donation, and matched three controls for each case. The donors filled out a questionnaire and one bacterial culture sample was taken from venepuncture forearm skin. RESULTS: The median total number of colony forming skin bacteria was significantly higher in the cases (224 CFUs per sample) than controls (105 CFU per sample). Staphylococcus aureus was significantly more often present on the skin in cases (49%) as compared to controls (7%). Regarding other bacterial genera, no difference between cases and controls was found. CONCLUSIONS: This study shows that our current guidelines for deferral of blood donors with skin disorders effectively identifies individuals with a high number of bacteria on their skin, as well as S. aureus carriers. However, deferral due to skin disorders had only a minor impact on blood product contamination when compared to other actions.

Novel PORCN mutations in focal dermal hypoplasia.

Focal dermal hypoplasia (FDH), Goltz or Goltz-Gorlin syndrome, is an X-linked dominant multisystem disorder characterized primarily by involvement of the skin, skeletal system and eyes. We screened for mutations in the PORCN gene in eight patients of Belgian and Finnish origin with firm clinical suspicion of FDH. First, we performed quantitative PCR (qPCR) analysis to define the copy number at this locus. Next, we sequenced the coding regions and flanking intronic sequences of the PORCN gene. Three de novo mutations were identified in our patients with FDH: a 150-kb deletion removing six genes including PORCN, as defined by qPCR and X-array-CGH, and two heterozygous missense mutations; c.992T>G (p.L331R) in exon 11 and c.1094G>A (p.R365Q) in exon 13 of the gene. Both point mutations changed highly conserved amino acids and were not found in 300 control X chromosomes. The three patients in whom mutations were identified all present with characteristic dermal findings together with limb manifestations, which were not seen in our mutation-negative patients. The clinical characteristics of our patients with PORCN mutations were compared with the previously reported mutation-positive cases. In this report, we summarize the literature on PORCN mutations and associated phenotypes.

Digital nerve somatosensory evoked potentials and MRI. Correlation analysis in patients with symptomatic cervical spine disorders.

OBJECTIVES: Analysis of the relationship between the symptoms, digital nerve somatosensory evoked potentials (D-SEP) and MRI, in patients with symptomatic cervical spine disorders (CSD). MATERIALS AND METHODS: MRI and D-SEP following electrical stimulation of digits I, III and V in 44 patients. RESULTS: Symptoms in the fingers correlated significantly with disk herniation at the corresponding cervical level and with spinal cord impingement at one or two adjacent rostral segments on MRI. D-SEP was abnormal in 52% of all patients. Among them, the groups with multiple and single level involved on MRI had 62% and 30% of abnormal somatosensory evoked potentials (SEP), respectively. Digit I-SEP abnormality was more often localized at the root level, while digit V-SEP at the spinal cord level above the dorsal nucleus. D-SEP correlated best with compression of the spinal cord at adjacent upper and especially the most rostral (C3-5) levels on MRI. CONCLUSIONS: Accurate correlation of D-SEP and symptoms with MRI is essential for correct localization of lesions in patients with CSD.

Tibial muscular dystrophy. Late adult-onset distal myopathy in 66 Finnish patients.

OBJECTIVE: To clarify the classification of two previously reported groups of patients with anterior tibial distal dystrophy, to find additional patients with the disease, and to describe the clinical features of this disease. DESIGN: National survey of the records of patients with neuromuscular diseases in Finland. Findings of selected patients were compared with those of previously reported cases. PATIENTS: Thirty-six previously described patients and 30 additional patients from the current survey, with 41 symptomatic patients and 25 subjectively asymptomatic affected relatives. RESULTS: There were 66 patients with late adult-onset tibial muscular dystrophy. Symptoms appear after the age of 35 years with reduced ankle dorsiflexion, and progress is slow without marked disability. Facial muscles, upper extremities, and proximal muscles are usually spared. Muscle biopsy results reveal nonspecific dystrophic changes in clinically affected muscles, and frequently severe adipose replacement in the anterior tibial muscles occurs. Asymptomatic muscles have mild myopathic changes only. Vacuolar degeneration is detected in a minority of patients. Electromyography shows profound myopathic changes in the anterior tibial muscle, but extensor brevis muscles are well preserved. Computed tomography or magnetic resonance imaging of muscles discloses marked involvement of tibial extensor muscles and focal patches of fatty degeneration in various asymptomatic muscles. Pedigree data suggest autosomal dominant inheritance. CONCLUSIONS: Tibial muscular dystrophy might represent a new form of distal myopathy and it is rather common, at least in Finland.

Crystal structure of lactitol (4-O-beta-D-galactopyranosyl-D-glucitol).

Lactitol, C12H24O11, is monoclinic, space group P2(1) with cell dimensions a = 7.614(1), b = 10.757(1), c = 9.370(1) A, beta = 108.19(1) degrees, and V = 729.0(1) A3, Z = 2, Dx = 1.57 Mg.m-3, lambda (Cu-K alpha) = 1.54056 A, mu = 1.166 mm-1, F(000) = 368, and T = 23 degrees. The structure was solved by direct methods and refined by least-squares calculations to R = 0.048 for 1510 unique observed reflections. There are one intra- and eight inter-molecular hydrogen bonds in the structure. Bond lengths and angles accord well with the mean values of related structures. The galactopyranosyl ring has a chair conformation.

Effects of acupuncture, cervical manipulation and NSAID therapy on dizziness and impaired head repositioning of suspected cervical origin: a pilot study.

In a single-subject experiment undertaken on 14 consecutive patients, the effects of acupuncture, cervical manipulation, no therapy, and NSAID-percutan application on kinesthetic sensibility, dizziness/vertigo and pain were studied in patients with dizziness/vertigo of suspected cervical origin. The ability to perceive position of the head with respect to the trunk was studied. The effects of different forms of therapy-and none-on dizziness and neck pain were compared, using a 100 mm visual analogue scale (VAS). Active head relocation by subjects with dizziness was significantly less precise than in the control group. Manipulation was the only treatment to diminish the duration of dizziness/vertigo complaints during the past 7 days and increased the cervical range of motion. Both acupuncture and manipulation reduced dizziness/vertigo on the VAS scale and had positive effects on active head repositioning. Ketoprofen percutan application and acupuncture both alleviated pain. The results of this study would suggest that spinal manipulation may impact most efficiently on the complex process of proprioception and dizziness of cervical origin.

Midazolam kinetics before, during and after cardiopulmonary bypass surgery.

Gas-chromatographically determined serum concentrations of midazolam were recorded before, during and after cardiopulmonary bypass in patients scheduled for a coronary artery bypass grafting operation. Following single 0.075 mg/kg (n = 6) and 0.15 mg/kg (n = 6) intravenous injections of midazolam, a mean distribution phase half-life of 3.4 and 4.4 min respectively was calculated. At the establishment of the bypass, a rapid drop in the concentration of midazolam was observed followed by a significant increase in concentration during the postperfusion period. The apparent mean elimination phase half-life (281 min) of midazolam was longer than that (about 120 min) measured in earlier works in young, healthy subjects. Thus the metabolism of midazolam during the postperfusion period appears to be slower.

Intra-articular botulinum toxin A for the treatment of osteoarthritic joint pain in dogs: a randomized, double-blinded, placebo-controlled clinical trial.

The aim of this study was to investigate the efficacy of intra-articular (IA) botulinum toxin A (IA BoNT A) for the treatment of osteoarthritic joint pain in dogs. The study was a placebo-controlled, randomized, double-blinded clinical trial with parallel group design and 12-week follow-up. Thirty-six dogs with chronic lameness due to stifle, hip or elbow osteoarthritis were randomized to receive an IA injection of 30IU of BoNT A or placebo. The main outcome variables were vertical impulse (VI) and peak vertical force (PVF) measured with a force platform, and Helsinki chronic pain index (HCPI). Subjective pain score and the need for rescue analgesics were secondary variables. The response to treatment was assessed as the change from baseline to each examination week. The variables were analyzed by ANOVA with repeated measurements and results were considered statistically significant if P ⩽ 0.05. The improvement from baseline to 12 weeks after baseline was statistically significant in VI, PVF and HCPI in the treatment group (P=0.001, P=0.054 and P=0.053, respectively). Additionally, there were statistically significant improvements in VI in the treatment group at 2, 4 and 8 weeks after baseline (P=0.037, P=0.016 and P=0.016, respectively). The difference between groups in improvement in VI was statistically significant at 12weeks after baseline (P=0.005). There was no significant change in the subjective pain score or in the requirement for rescue analgesics in either group. No major adverse events thought to be related to trial protocol were detected. These results suggest that IA BoNT A has some efficacy in reducing osteoarthritic pain in dogs.

Combined low-saturated fat intake and high fitness may counterbalance diabetogenic effects of obesity: the DR's EXTRA Study.

We report associations of saturated fat (SF) intake with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), concurrent IFG+IGT and type 2 diabetes (T2DM) at different levels of cardiorespiratory fitness and body mass index (BMI). In a population-based sample (n=1261, age 58-78 years), oral glucose tolerance, 4-day food intake and maximal oxygen uptake were measured. High intake of SF (>11.4 E%) was associated with elevated risk for IFG (4.36; 1.93-9.88), concurrent IFG+IGT (6.03; 1.25-29.20) and T2DM (4.77; 1.93-11.82) in the category of high BMI (>26.5) and high fitness, whereas there was no significantly elevated risk in individuals reporting low intake of SF. Concurrent high BMI and low fitness were associated with elevated risks. In general, SF intake and fitness did not differentiate the risk of abnormal glucose metabolism among subjects with low BMI. Limited intake of SF may protect from diabetogenic effects of adiposity, but only in individuals with high level of fitness.

The histopathology of idiopathic pulmonary fibrosis in West Highland white terriers shares features of both non-specific interstitial pneumonia and usual interstitial pneumonia in man.

Idiopathic pulmonary fibrosis (IPF) in West Highland white terriers (WHWTs) is a breed-related, spontaneously arising disease that is a potential animal model for IPF in man. Histopathological similarity between IPF in WHWTs and usual interstitial pneumonia (UIP), the histopathological correlate for IPF in man, has not been confirmed and histological features of non-specific interstitial pneumonia (NSIP), another form of human idiopathic interstitial pneumonia, have been reported in WHWTs with IPF. This study describes the pulmonary histopathological findings in 18 WHWTs with IPF, including lobe-specific samples in nine of the dogs. The canine lesions and their distribution pattern are compared with histopathological characteristics in samples of human UIP and NSIP. Underlying diffuse mature fibrosis, resembling human NSIP more than UIP, was seen in the lungs of all dogs with IPF. Additionally, the majority of dogs with IPF showed multifocal areas of accentuated subpleural and peribronchiolar fibrosis with occasional 'honeycombing' and profound alveolar epithelial changes, reminiscent of human UIP and not commonly seen in NSIP. Interstitial fibroblastic foci, characteristic of UIP, were not seen in WHWTs with IPF. Progressive fibrosis, with intra-alveolar organizing fibrosis alongside interstitial mature collagen deposition, was present within the more severely affected areas of lung in WHWTs with IPF. Severe pulmonary lesions were seen more commonly in the caudal than in the cranial lung lobes.

Dietary associations with prediabetic states--the DR's EXTRA Study (ISRCTN45977199).

BACKGROUND/OBJECTIVES: Impaired fasting plasma glucose (IFG) and impaired glucose tolerance (IGT) predict development of type 2 diabetes (T2D), but display different pathophysiology for T2D. We studied the association of selected food items and nutrients with IFG, IGT and combined IFG and IGT (IFG+IGT), independent of cardiorespiratory fitness (VO(2max)). SUBJECTS/METHODS: In a population-based sample of 1261 individuals, aged 58-78 years, we identified 126 subjects with IFG, 97 with IGT and 49 with simultaneous IFG and IGT by an oral glucose tolerance test. Dietary intake was assessed by 4-day food records. Cardiorespiratory fitness was assessed by defining maximal oxygen uptake (VO(2max)) from respiratory gas analysis during a maximal symptom-limited exercise stress test on a bicycle ergometer. RESULTS: Increased intake of saturated fat was associated with higher odds for IFG (OR 1.07; 1.01-1.14) after adjustment for age, gender, VO(2max) and energy misreporting variable. Consumption of additional whole-grain bread (50 g/1000 kcal) and intake of dietary fiber (g/1000 kcal) were inversely associated with IGT (OR 0.61; 0.41-0.92, OR 0.91; CI 0.85-0.97, respectively). CONCLUSION: Dietary fiber and sources of cereal fiber are negatively associated with IGT, and saturated fat intake is positively associated with IFG, but not with IGT. The present data give practical dietary means at the population level for the elimination of prediabetic conditions.

Serum and bronchoalveolar lavage fluid endothelin-1 concentrations as diagnostic biomarkers of canine idiopathic pulmonary fibrosis.

BACKGROUND: Diagnosis of canine idiopathic pulmonary fibrosis (IPF) is challenging. Endothelin-1 (ET1) is a biomarker of IPF in humans, but whether ET1 can detect and differentiate IPF from other canine respiratory diseases is unknown. OBJECTIVE: To evaluate whether measurement of the concentration of ET1 in serum and bronchoalveolar lavage fluid (BALF) can be used to distinguish canine IPF from chronic bronchitis (CB) and eosinophilic bronchopneumopathy (EBP). ANIMALS: Twelve dogs with IPF, 10 dogs with CB, 6 dogs with EBP, 13 privately owned healthy West Highland White Terriers (WHWT), and 9 healthy Beagle dogs. METHODS: Prospective, case control study. ET1 concentration was determined by ELISA in serum and in BALF. RESULTS: No significant difference in serum ET1 concentration was detected between healthy Beagle dogs and WHWT. Serum ET1 concentration was higher in dogs with IPF (median interquartile range; 2.32 pg/mL, 2.05-3.38) than healthy Beagle dogs (1.28, 1.07-1.53; P < .001), healthy WHWT (1.56, 1.25-1.85; P < .001), dogs with EBP (0.94 0.68-1.01; P = .001), and dogs with CB (1.54 0.74-1.82; P = .005). BALF ET1 concentration was below the detection limit in healthy WHWT and in dogs with CB, whereas it was measurable in all dogs with IPF. A cut-off serum concentration of 1.8 pg/mL had a sensitivity of 100% and a specificity of 81.2% for detection of IPF, with an area under the receiver operating characteristic curve of 0.818. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum ET1 can differentiate dogs with IPF from dogs with EBP or CB. ET1 can be detected in BALF of dogs with IPF.

Clinical, bronchoscopic, histopathologic, diagnostic imaging, and arterial oxygenation findings in West Highland White Terriers with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, interstitial lung disease primarily affecting West Highland White Terriers (WHWTs). OBJECTIVE: To describe the clinicopathological and diagnostic imaging features in WHWTs with IPF. ANIMALS: Twelve WHWTs with IPF and 14 healthy control WHWTs. METHOD: Prospective study. Clinical signs and findings of physical examination, blood and arterial blood gas analyses, radiography, high-resolution computed tomography (HRCT), bronchoscopy and bronchoalveolar lavage (BAL) of IPF dogs were obtained and compared with controls. Histopathologic changes in IPF dogs were evaluated. RESULTS: Mean partial pressure of oxygen was significantly lower in IPF (mean ± SD, 65.5 ± 15.4 mmHg) than in controls (99.1 ± 7.8 mmHg, P<.001). The alveolar-arterial oxygen gradient was significantly higher in IPF (50.1 ± 17.3 mmHg) than in controls (17.5 ± 4.9 mmHg, P<.001). In HRCT, ground glass opacity (GGO) was detected in all IPF dogs, traction bronchiectasis in 4, and honeycombing in 1. Bronchoscopic airway changes were noted in all IPF dogs. On BAL fluid (BALF) cytology, the total cell count (TCC) was higher in IPF dogs, and the numbers but not the percentages of macrophages, neutrophils, and mast cells were increased. On histopathology, multifocal or diffuse interstitial fibrosis, type II pneumocyte hyperplasia, prominent intraalveolar macrophages, distortion of alveolar architecture, and emphysematous change were detected. CONCLUSION AND CLINICAL IMPORTANCE: IPF causes substantial hypoxemia. In HRCT, GGO is a consistent finding. IPF dogs have concurrent airway changes and an increase in BALF TCC.

Food consumption, nutrient intake and the risk of having metabolic syndrome: the DR's EXTRA Study.

BACKGROUND: The associations of different components of diet with metabolic syndrome (MetS) are largely unknown. We therefore studied the associations of intakes of selected food items and nutrients with the risk of having MetS. METHODS: The participants were a representative population sample of 1334 individuals (671 women, 663 men) 57-78 years of age. Dietary intake was assessed by a 4-day food record. MetS was defined by the National Cholesterol Education Program criteria. RESULTS: Consumption of vegetables, non-root vegetables, legumes and nuts berries and fish had an inverse and consumption of sausage had a direct association with the risk of having MetS in men after adjustment for age, smoking and alcohol consumption. Consumption of vegetables and non-root vegetables had an inverse and consumption of sausage had a direct association with the risk of having MetS in women after these adjustments. However, after further adjustment for maximal oxygen uptake (VO2(max)) most of these associations vanished. Men in the highest third of consumption of berries, fish, and legumes and nuts had 49, 37 and 44% lower risk of having MetS, respectively, than those in the lowest third after further adjustment for VO2(max). Women in the highest third of sausage consumption had a 72% higher risk of having MetS than non-consumers. CONCLUSIONS: Consumption of legumes and nuts, berries and fish was inversely associated with MetS in men. Consumption of sausage was directly associated with MetS in women. VO2(max) seems to be a strong confounding factor between food consumption and MetS.