Behaviour management problems in Finnish children with operated congenital heart disease: a practice-based study.

PURPOSE: This retrospective, practice-based study investigates behaviour management problems (BMPs) in dental care among Finnish children with operated congenital heart disease (CHD). METHODS: All the heart-operated children born between the years 1997 and 1999 were identified in the national ProCardio database (n = 570). Primary dental care records were requested from this population and were eventually received from 211 patients. Information on gender, diagnosis, number of heart operations and perioperative care were collected from the ProCardio database, and the CHDs were categorised as shunting/stenotic/complex/other defects. Data on BMP/dental fear, oral conscious sedation, dental general anaesthesia (DGA) and past and present caries indices at 6, 12 and 15 years (d/D, dmft/DMFT) were assessed. RESULTS: Notes on behaviour management problems or dental fear were found in 19% of the study population. BMPs in dental care were more frequent among boys. Children with re-operations, longer post-operative intensive care stay and hospitalisation, and complications had not more BMP than others. Those children diagnosed with syndromes had more BMP often than the rest. Past and present caries experience were significantly associated with BMP, need of oral conscious sedation and DGA. Oral conscious sedation, nitrogen oxide sedation and dental general anaesthesia were used in 17/211, 2/221 and 24/211 CHD patients, respectively. CONCLUSION: Dental caries remains a main factor associated with BMP in the CHD population. Need for oral conscious sedation and DGA were rather common. To maintain a good oral health and to avoid development of BMP, CHD children benefit from focus in health promotion and preventive care.

Dental caries and attendance to dental care in Finnish children with operated congenital heart disease. A practice based follow-up study.

PURPOSE: Oral health of children with congenital heart disease (CHD) is of utmost importance. This study aimed to investigate the prevalence of dental caries and attendance to dental care in Finnish heart-operated CHD patients born in 1997-1999. METHODS: The cohort of children born in 1997-1999 was selected using a national register on all heart-operated children in Finland. Gender, general health problems, diagnosis, type of the heart defect (shunting, stenotic and complex defects), and number of operations were available and included in the analyses. Dental records from primary health care were collected from municipalities with their permission. The data comprised of the number of dental examinations and data on caries status (dt, DT, dmft, DMFT) at the age of 7 (grade 1), 11 (grade 5) and 15 (grade 8) years and at the most recent examination. The control group consisted of dental data on patients born in 1997-1999 provided by the City of Oulu, Finland (n = 3356). RESULTS: Oral patient records of 215/570 children were obtained. The difference between the defect types was statistically significant both for DT (p = 0.046) and DMFT (p = 0.009) at the age of 15 (grade 8). The prevalence of caries did not differ between the study population and the controls. High present and past caries experiences were not associated with higher number of visits to oral health care, especially to oral hygienist, or with oral health promotion. National obligations concerning dental visits were not implemented in all municipalities. CONCLUSION: There seems to be a need for oral health promotion and preventive means implemented by oral hygienists among those with CHD.

Presence of CD3+ and CD79a+ Lymphocytes in the Pituitary Gland of Dogs at Post-mortem Examination.

Hypophysitis has been reported occasionally in dogs, with most cases resembling primary lymphocytic hypophysitis in man. Although it is generally assumed that lymphocytes are not present normally in the canine pituitary gland, few studies have investigated this hypothesis. However, lymphocytes are recognized in the pituitary gland of people and horses without signs of pituitary disease. It is unknown to what degree lymphocyte infiltration of the pituitary gland might occur as an incidental finding in dogs. The aim of the present study was to investigate the presence and distribution of lymphocytes in the pituitary gland of dogs without clinical suspicion of pituitary disease. Twenty dogs were subjected to routine necropsy examination. Formalin-fixed and paraffin wax-embedded sections of pituitary were stained with haematoxylin and eosin (HE) or subjected to immunohistochemistry (IHC) using primary antibodies specific for the T-cell marker CD3 and the B-cell marker CD79a. The number of CD3+ and CD79a+ cells per area unit (CPA) was determined for different pituitary regions. Two dogs had extensive neoplastic lesions in the pituitary gland and were excluded from analysis. In the remaining 18 dogs, occasional scattered CD3+ cells were found in the pituitary gland. There was a significant difference in CD3+ CPA between pituitary regions (P = 0.001). The highest CD3+ CPA was found in the pars tuberalis (median 41.3 cells/mm2, interquartile range 20.9-50.5 cells/mm2). In six of the 18 dogs (33%), CD79a+ cells were detected in small number (median total cell number 0 cells/section, interquartile range 0-1.0 cells/section). This study shows that T cell, and fewer B cells, may be found in the pituitary gland of dogs without clinical suspicion of pituitary disease. Regional difference in T-cell density, with the highest CD3+ CPA in the pars tuberalis, may imply regional immunoregulatory functions in the canine pituitary gland.

Administration of sulfatide to ameliorate type I diabetes in non-obese diabetic mice.

The endogenous glycosphingolipid sulfatide is a ligand for CD1d-restricted type II natural killer T (NKT) lymphocytes. Through the action of these cells,sulfatide treatment has been shown to modulate the immune response in mouse models for autoimmune diseases, infections and tumour immunity. Sulfatide exists naturally in different organs including the pancreas, where sulfatide colocalizes with insulin within the Langerhans islet b-cells, targets for the immune destruction in type 1 diabetes (T1D). Human T1D patients, but not patients with type 2 diabetes nor healthy individuals, have autoantibodies against sulfatide in serum, suggesting that sulfatide induces an immune response in the natural course of T1D in humans. Here, we investigate sulfatide as an autoantigen and a modulator of autoimmune disease in the murine model forT1D, the non-obese diabetic (NOD) mice. We demonstrate that aged NOD mice displayed serum autoantibody reactivity to sulfatide; however, this reactivity did not correlate with onset of T1D. Repeated administration of sulfatide did not result in an increase in serum reactivity to sulfatide. Moreover, a multidose sulfatide treatment of female NOD mice initiated at an early (5 weeks of age),intermediate (8 weeks of age) or late (12 weeks of age) phase of T1D progression did not influence the incidence of disease. Thus, we demonstrate that a fraction of NOD mice develop autoantibody reactivity to sulfatide; however, we fail to demonstrate that sulfatide treatment reduces the incidence of T1D in this mouse strain.

Increased CSF sulfatide levels and serum glycosphingolipid antibody levels in healthy siblings of multiple sclerosis patients.

A proportion of healthy siblings of multiple sclerosis (MS) patients have an oligoclonal immunological reaction in their cerebrospinal fluid (CSF) termed the "MS oligoclonal trait". The CSF levels of the major myelin glycosphingolipid sulfatide and serum antibodies against the glycosphingolipids sulfatide and galactosylceramide were recently reported to be increased in MS patients. We studied the levels of these substances in pairs of 46 patients and their 46 healthy siblings and 50 unrelated healthy blood donors (HBD). The sulfatide concentration in CSF was assayed by thin layer chromatography and immunostaining, and the concentration of galactosylceramide by densitometry after thin layer chromatography. Anti-glycosphingolipid antibody levels were assayed by ELISA. In the healthy siblings, the CSF sulfatide concentrations were markedly increased (p<0.001, age adjusted p=0.025), and the serum IgM anti-GalCer antibodies were increased in healthy siblings compared with HBD (p=0.02). The increased sulfatide or antibody levels did not co-segregate with the "MS oligoclonal trait" or the HLA-DR15 phenotype. In conclusion, a proportion of healthy siblings of MS patients have increased CSF sulfatide and anti-glycosphingolipid antibody levels, which may, analogous to the "MS oligoclonal trait", constitute an "MS glycosphingolipid endophenotype". Endophenotypes could potentially simplify the genetics of complex disorders.

Altered distribution of the gangliosides GM1 and GM2 in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder where ß-amyloid tends to aggregate and form plaques. Lipid raft-associated ganglioside GM1 has been suggested to facilitate ß-amyloid aggregation; furthermore, GM1 and GM2 are increased in lipid rafts isolated from cerebral cortex of AD cases. AIM/METHOD: The distribution of GM1 and GM2 was studied by immunohistochemistry in the frontal and temporal cortex of AD cases. Frontotemporal dementia (FTD) was included as a contrast group. RESULTS: The distribution of GM1 and GM2 changes during the process of AD (n = 5) and FTD (n = 3) compared to controls (n = 5). Altered location of the GM1-positive small circular structures seems to be associated with myelin degradation. In the grey matter, the staining of GM1-positive plasma membranes might reflect neuronal loss in the AD/FTD tissue. The GM1-positive compact bundles were only visible in cells located in the AD frontal grey matter, possibly reflecting raft formation of GM1 and thus a pathological connection. Furthermore, our results suggest GM2 to be enriched within vesicles of pyramidal neurons of the AD/FTD brain. CONCLUSION: Our study supports the biochemical finding of ganglioside accumulation in cellular membranes of AD patients and shows a redistribution of these molecules.

Myelin glycosphingolipid immunoreactivity and CSF levels in multiple sclerosis.

OBJECTIVES: Patients with multiple sclerosis were reported to harbour antibodies not only against proteins and glycoproteins but also against glycolipids, including sulfatide and galactosylceramide (GalCer), the two major glycosphingolipids of myelin. However, previous results were inconsistent concerning glycosphingolipid levels, antibody type, dominance of serum or Cerebrospinal fluid compartments and relationship to the multiple sclerosis (MS) course. RESULTS: We hereby report that the cerebrospinal fluid levels of sulfatide were increased in patients with MS (n = 46) compared with controls (n = 50, P < 0.001). In addition, patients had higher serum IgM anti-glycosphingolipid titres than controls (P = 0.03 for sulfatide, <0.001 for GalCer), while the anti-glycosphingolipid IgM antibodies in the cerebrospinal fluid were essentially normal. However, in seven of 46 patients cerebrospinal fluid IgG antibodies against GalCer (P = 0.004) could be detected, which was not found in any of the control individuals, and this finding might mirror the occurrence of more specific B-cell clones behind the blood-brain barrier. CONCLUSIONS: The IgM immunoreactivity in serum did not show any relationship to the type of course or severity of MS, arguing against a phenomenon secondary to myelin damage. Thus, the IgM antibody findings are compatible with an early antigen challenge or autoimmunity associated with natural antibodies.

Dental caries in adolescents with attention deficit hyperactivity disorder: a population-based follow-up study.

This study tested the hypothesis that adolescents with attention deficit hyperactivity disorder (ADHD) exhibit a higher prevalence of caries than adolescents in a control group. Thirty-two adolescents with ADHD and a control group of 55 adolescents from a population-based sample, all 17 yr of age, underwent a clinical and radiographic dental examination. The mean ± SD number of decayed surfaces (DS) was 2.0 ± 2.2 in adolescents with ADHD and 0.9 ± 1.4 in adolescents of the control group. Thirty-one per cent of the adolescents in the ADHD group had no new caries lesions (DS = 0) compared with 62% in the control group. Six per cent of the adolescents in the ADHD group were caries free [decayed, missing or filled surfaces (DMFS) = 0] compared with 29% in the control group. Adolescents with ADHD also had a higher percentage of gingival sites that exhibited bleeding on probing compared with the control group: 35 ± 39% vs. 16 ± 24% (mean ± SD), respectively. At 17 yr of age, adolescents with ADHD exhibited a statistically significantly higher prevalence of caries compared with an age-matched control group. Adolescents with ADHD need more support regarding oral hygiene and dietary habits. They should be followed up with shorter intervals between dental examinations to prevent caries progression during adulthood.

Effects of age and soccer expertise on general tests of perceptual and motor performance among adolescent soccer players.

This study of perceptual and motor skills in soccer players was conducted on adolescent males. The goals were to monitor the development of general perceptual motor skills in nonsoccer-playing and soccer-playing groups (n = 245), to examine the relationship between physical maturity and general perceptual motor skills (n = 41), and to compare the differences in general perceptual motor skills between groups with different soccer expertise (n = 142). The measured variables were simple reaction time, peripheral awareness, eye-hand-foot coordination, and testosterone blood level. The results suggested that general perceptual motor skills improved with age, the development of these skills was related to participants' blood testosterone concentration (especially between 12 and 14 years), and general perceptual motor skills improved with soccer expertise. However, the differences between subelite and elite soccer players were not meaningful enough to encourage practitioners to test general perceptual motor skills on a large scale when evaluating the potential of young players.

Outcome after severe brain damage, what makes the difference?

OBJECTIVE: To assess and compare the consequences for outcome in terms of the dimensions of activity and participation for two groups: group A, which received early formalized rehabilitation, and group B, which received late or no formalized rehabilitation. RESEARCH DESIGN: A cross-sectional study. PROCEDURE: Twenty-six patients (A: n = 14 and B: n = 12) with severe brain damage were included. The participants were assessed a mean of 26.6 months (SD 7.1, median 25, range 14-41) after the incident using the structured form for the Swedish Neuro database, the Glasgow Outcome Scale (GOS), the Extended Glasgow Outcome Scale (GOSE) and the Functional Independence Measure (FIM). RESULTS: The study reveals a better outcome for group A. No patient remained in a vegetative state in group A as compared with three in group B. In group A, 50% were independent as compared with 17% in group B. The frequency of return to work was 43% in group A, but no patient in group B had returned to work.

Involvement of sulfatide in beta cells and type 1 and type 2 diabetes.

Mammalian tissues express beta-isoforms of glycosphingolipids and, among these, sulfatide (sulphated galactosylceramide) is present in the beta cells, and it is here that the short fatty acid chain (C16) isoform is predominately found. In vitro studies have shown that sulfatide preserves insulin crystals and facilitates insulin monomerisation under certain biochemical conditions. It also activates beta cell potassium channels and moderates insulin secretion. Anti-sulfatide antibodies are seen in type 1 diabetes, and immunological presentation of glycosphingolipids by the non-classical CD1 molecules has recently been reported. It is via this mechanism that alpha-galactosylceramide and sulfatide are able to influence the innate immune system and inhibit autoimmunity, possibly through regulatory natural killer T cells. Administration of sulfatide substantially reduces the incidence of diabetes in non-obese diabetic mice and prevents antigen-induced experimental autoimmune encephalomyelitis in wild-type mice. Sulfatide has specific anti-inflammatory properties, increasing the number of CD3+CD25+ regulatory T cells and reducing production of several cytokines, including TNF-alpha. Patients with type 2 diabetes have low serum concentrations of sulfatide, and some animal models of type 2 diabetes have low pancreatic expression of C16:0 sulfatide; administration of this increases insulin secretion and improves first-phase insulin response in Zucker fatty rats. Glycosphingolipids in general, and sulfatide in particular, appear relevant to both type 1 and type 2 diabetes.

Nanocrystalline metal/carbon composites produced by supersonic cluster beam deposition.

In this work we show that supersonic cluster beam deposition is a viable method for the synthesis of nanocrystalline metal/carbon composites. By assembling carbon and metallic clusters seeded in a supersonic beam, we have grown films consisting of metal nanoparticles embedded in a nano-structured carbon matrix. Samples containing 3d transition metals (Ti, Ni) and noble metals (Au, Pd, Pt) with different metal abundances, particle size and dilution have been characterized by transmission electron microscopy. The influence of different metals on the structure of the carbon matrix has been investigated. Spatially resolved ultraviolet photoemission electron spectroscopy showed substantial surface oxidation of 3d transition metal clusters. On a micrometric scale, the spatial distribution of the metallic nanoparticles appeared to be homogeneous.

Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project.

AIMS: The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. METHODS: A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. RESULTS: Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). CONCLUSIONS: We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.

Rotavirus infections and development of diabetes-associated autoantibodies during the first 2 years of life.

Rotavirus, the most common cause of childhood gastroenteritis, has been implicated as one of the viral triggers of diabetes-associated autoimmunity. To study the possible association between rotavirus infections and the development of diabetes-associated autoantibodies, we measured the prevalence of rotavirus antibodies in serum samples collected at 3-6-month intervals up to the age of 2 years from 177 children selected from consecutive newborns because they carried HLA-DQB1 alleles associated with increased risk for type 1 diabetes. Twenty-nine of the children developed at least two of four diabetes-associated autoantibodies (ICA, IAA, GADA or IA-2A) during the first 2 years of life (the cases), whereas 148 children remained autoantibody-negative matched with the cases for date of birth, gender, living region and HLA-DQB1 alleles. The temporal association between the development of the first-appearing diabetes-associated autoantibody and rotavirus infections was studied by analysing whether the cases had a diagnostic increase in rotavirus antibody titre more often during the 6-month period that preceded seroconversion to autoantibody positivity than the controls. By the age of 12 months one of the 13 case children (7%), who had a serum sample drawn at that age and who had developed at least one type of diabetes-associated autoantibodies, had experienced a rotavirus infection, while 12 of the 61 (20%) autoantibody-negative control children had had a rotavirus infection. By 18 months, four of the 22 autoantibody-positive cases (18%) and 18 of the 89 controls (20%) had rotavirus antibodies, and by the age of 24 months the respective numbers were five of the 27 cases (19%) and 32 of the 113 (28%) controls. A rotavirus infection occurred during the 6 months preceding the sample which was positive for an autoantibody in four of the 25 periods (16%) for which both necessary samples were available, while the controls had a rotavirus infection during 55 of the 370-such periods (15%). Accordingly, our data suggest that rotavirus infections are unlikely triggers of beta-cell autoimmunity in young children with genetic susceptibility to type 1 diabetes.

Identification of defensins in human lymphocyte nuclei.

The cell nucleus plays an essential role in all aspects of cell function and regulation. Most of the nuclear proteins/peptides are synthesized in the cytoplasm and transported into the nucleus through the nuclear pore complexes. The nuclear proteins/peptides conjugate with each other and interact in transcriptional activation/inactivation. Several of the high molecular mass transcription factors (> 30 kDa) have been identified and characterized. However, the information on the low molecular mass proteins/peptides of the nucleus is limited. We have investigated these low molecular mass proteins/peptides from the nucleus of human peripheral blood lymphocytes using reversed-phase high-performance liquid chromatography (RP-HPLC). The HPLC fractions were further analysed by matrix assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry, electrospray ionization time of flight (ESI-TOF) mass spectrometry and electrospray ionization fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry for mass determination. Using this combination of mass spectrometry techniques and microsequence analysis, we have shown that human lymphocyte nuclei contain defensins, a mixture of human neutrophil granule peptide 1, 2 and 3.

3D visualization library for multimodal medical images.

This study focuses on three-dimensional (3D) presentations of medical images such as magnetic resonance (MR) images and computed tomography (CT) images. Also multimodal presentations of medical images and signals, including different visualization techniques are considered. A C++ class library together with graphical user interfaces was developed for presenting the results. The implemented software operates in PC/Windows environment. It was tested with various medical images including raw MR and CT data and segmented images, and was applied in a hospital environment. The software operates relatively fast and the quality of resulting pictures is adequate for all tested medical applications. Further applications of 3D presentations in clinical medicine are considered.

Descriptive physiological data on a sleep bruxism population.

We studied 24 bruxers (23-67 years old). They often complained of orofacial and bodily pain and presented autonomic symptoms (sweating 23%, palpitations at night 62%, decreased libido 50%); 19% had increased blood pressure requiring treatment, and 65% reported frequent headaches in the morning. Deep sleep and rapid eye movement (REM) were delayed. An average of 167 orofacial episodes developed during the night. The mean number of masseter bursts strictly defined as bruxism was 79, the mean delay for the first occurrence after sleep onset 18 minutes. The majority of bruxism occurred in stage 2 sleep and REM sleep. The mean number of shifts of sleep stages was 70, one-third occurring within the first minute following a bruxing episode, and 15% of bruxing episodes developed after a shift in sleep stage. Electroencephalogram showed alpha-delta pattern in 15% of the subjects. Short-lasting alpha activity was often encountered during the 10 seconds preceding the development of a bruxing episode. Tachycardia developed at its onset, persisting for 10 seconds. We suggest that, as a minor alarm response to endogenous/exogenous stimuli, arousal develops and is often followed by motor activation, such as a burst of bruxing, with, as in any situation when motor activity suddenly increases, a secondary increase of heart activity.

Once-daily controlled release remoxipride is equieffective with twice-daily immediate release remoxipride in the treatment of schizophrenia.

A controlled release (CR) formulation of remoxipride (Roxiam(®), Astra) given once-daily was compared to immediate release (IR) remoxipride given twice-daily, with respect to efficacy and tolerability, in a 4-week multicentre parallel-group dose titration (200-600 mg/day) study with acutely ill schizophrenic patients. Forty- three patients received remoxipride CR (mean dose 344 mg/day) and 49 patients received remoxipride IR (mean dose 346 mg/day). Efficacy was assessed using the Kolakowska version of the Brief Psychiatric Rating Scale (BPRS score of ≥ 18 points at entry) and the Clinical Global Impression scale (CGI), while extrapyramidal symptoms were rated using the Simpson and Angus scale. Both formulations of remoxipride produced clinical improvement, with the BPRS median total score falling from 35 at baseline to 16 at last rating in the remoxipride CR group, and from 33 to 12.5 in the remoxipride IR group. More than 70% of the patients in both groups were assessed as 'much improved' or 'very much improved' according to the CGI scale. Both formulations of remoxipride were well-tolerated, with a low incidence of treatment-emergent adverse symptoms, including extrapyramidal side effects. No statistically significant differences were detected between the treatment groups with regard to efficacy, safety or tolerability.

A placebo controlled trial of remoxipride in the prevention of relapse in chronic schizophrenia.

Sixty-two DSM III chronic schizophrenic inpatients were selected for a double-blind, placebo controlled, multi-centre, relapse prevention study of remoxipride, a selective dopamine (D2)-receptor antagonist. After a 1 month placebo washout, 23 patients had relapsed and were withdrawn. Of the remaining patients 19 were randomised to remoxipride (150-300 mg daily) and 20 to placebo. Their median age was 58 years, 26 were male, and the median duration of illness was 33 years. After 24 weeks a further total of 8 remoxipride and 17 placebo patients had been withdrawn. Excluding three patients withdrawn for reasons other than relapse, the comparative relapse rates were 37% and 75%, respectively (P = 0.015). Efficacy analyses using clinical global impression (P = 0.04) and change in BPRS scores (P = 0.016) were in favour of remoxipride. Extrapyramidal symptoms were minimal in both groups. Treatment emergent adverse events were similar in the two groups. Remoxipride is therefore of potential value as a safe drug which is both effective and well tolerated in the long term management of chronic schizophrenic patients.