Familial dyslexia: neurocognitive and genetic correlation in a large Finnish family

Neuropsychological findings of individuals with dyslexia (n=24) from a large, three-generation Finnish family are presented. We have previously performed whole genome linkage scanning in this family and found that dyslexia in this kindred segregates with a single locus in the pericentromeric area of chromosome 3. Those included in the analyses were carefully evaluated for general cognitive ability, reading and spelling skills, and reading-related neurocognitive skills. The neurocognitive type of dyslexia segregating in this family consisted of deficits in phonological awareness, verbal short-term memory, and rapid naming. Severe dyslexia also seemed to be connected with a general language difficulty and was most common in the eldest generation.     

Treatment of late Lyme borreliosis

The aim of this study was to develop a treatment for late Lyme borreliosis and to compare the clinical results with serological findings before and after treatment. It was done in the land Islands (population 25000), a region endemic for Lyme borreliosis. The patients were the first consecutive 100 patients from the land Islands with late Lyme borreliosis. They were followed for at least 1 year after treatment. The clinical results of treatment were compared with results of analyses of flagellar IgG antibodies to Borrelia burgdorferi done at the time of diagnosis before treatment and up to 12 months afterwards. Short periods of treatment were not generally effective. The outcome was successful in four of 13 treatments with 14 days of intravenous ceftriaxone alone, in 50 of 56 assessable treatments with ceftriaxone followed by 100 days of amoxycillin plus probenecid, and in 19 of 23 completed treatments with ceftriaxone followed by 100 days of cephadroxil. Titres of IgG antibodies to B. burgdorferi flagella declined significantly after 6 and 12 months in the patients who had successful treatments. All patients whose final titres were less than 30% of the initial titre were in the successful group. Their titres usually remained above the upper limit of normal for a long time but a decline to a value of less than 30% of that before treatment was always a sign of cure.     

Lifestyle strategies for weight control: experience from the Finnish Diabetes Prevention Study

Currently, in many European countries more than half the adult population is overweight; it hass become 'abnormal' to be of 'normal weight'. The risk of type 2 diabetes, CVD, hypertension and certain forms of cancer increase with increasing weight. Biological evolution has produced body-fat-regulating mechanisms that are more powerful in protecting against weight loss than against weight gain. The current environment offers constant availability of affordable palatable energy-rich foods, with no need to consume the energy through physical activity. The 'obesogenic' environment is to some extent a political issue, but it has been shown that the healthcare system can also have a role in preventing obesity-related morbidity. The Finnish Diabetes Prevention Study was the first controlled randomised study to show that individualised lifestyle counselling of individuals with high risk of developing type 2 diabetes can influence diet, physical activity and body weight, and that type 2 diabetes can be prevented, or at least postponed. Most importantly, lifestyle changes do not have to be extreme. If the population would adopt a lifestyle in line with the official nutrition recommendations, the obesity and diabetes trend could at least be stabilised.     

European prices of newly launched reimbursable pharmaceuticals--a pilot study

High prices of new pharmaceuticals play an important part in rapidly rising pharmaceutical costs. Many countries try to curb these rising costs through control of the price of reimbursable medicines. There is, however, little internationally comparable information on prices. This study aimed to examine the prices of new, reimbursable pharmaceuticals in the EU member states. Price data were collected from eight products authorised by the EC in 2000. The prices of these products varied considerably. Wholesale prices were highest in those countries where manufacturers are free to set the prices of their products. Pharmacy margins and taxes, however, change the ranking of the most expensive or the cheapest countries.     

Characterization of breast milk received by infants with gross blood in stools

OBJECTIVE: The aim of this study was to ascertain factors that might be protective of the appearance of gross blood in the stools of breast-fed infants. METHODS: Logistic regression models were formed to search for variables possibly explaining the condition. In addition to the analyzed breast milk factors, mother's allergic disease was introduced into the models to control for its possible confounding effect. The breast milk samples, collected from mothers of infants with gross blood in stools (n = 23) and from mothers of healthy age-matched infants (n = 71), were analyzed for concentrations of transforming growth factor-beta2, tumor necrosis factor-alpha, interleukin (IL)-4, IL-10, prostaglandin (PG)E2, cysteinyl leukotrienes (Cys-LTs) and fatty acid composition. RESULTS AND CONCLUSIONS: Increase in the concentrations of PGE2 and Cys-LTs in the breast milk together with mother's allergic disease reduced the likelihood of gross blood in stools in the breast-fed infant. The results suggest that no single factor, but a combination of immunomodulatory factors may protect the child from gross blood in the stools of breast-fed infants. Allergic disease was not a risk factor as mother's allergic disease appeared to counterbalance the gross blood in stools. Due to the preliminary nature of the study, the results need to be verified in a larger setting. The challenge for the future lies in identifying of such active compounds for dietary modification to enforce particularly the properties of the breast milk which are immunoprotective for the infant and to reduce the likelihood of intestinal disorders in at risk infants.     

Cathepsin D-deficient Drosophila recapitulate the key features of neuronal ceroid lipofuscinoses

Neuronal ceroid lipofuscinoses (NCLs) are a group of lysosomal storage disorders characterized pathologically by neuronal accumulation of autofluorescent storage material and neurodegeneration. An ovine NCL form is caused by a recessive point mutation in the cathepsin D gene, which encodes a lysosomal aspartyl protease. This mutation results in typical NCL pathology with neurodegeneration and characteristic neuronal storage material. We have generated a Drosophila NCL model by inactivating the conserved Drosophila cathepsin D homolog. We report here that cathepsin D mutant flies exhibit the key features of NCLs. They show progressive neuronal accumulation of autofluorescent storage inclusions, which are also positive for periodic acid Schiff and luxol fast blue stains. Ultrastructurally, the storage material is composed of membrane-bound granular electron-dense material, similar to the granular osmiophilic deposits found in the human infantile and ovine congenital NCL forms. In addition, cathepsin D mutant flies show modest age-dependent neurodegeneration. Our results suggest that the metabolic pathway leading to NCL pathology is highly conserved during evolution, and that cathepsin D mutant flies can be used to study the pathogenesis of NCLs.     

Lung volumes in infants who had mild to moderate bronchopulmonary dysplasia

New bronchopulmonary dysplasia (BPD) has been suggested to be a maldevelopment sequence with reduced alveolarisation of the lungs; affected infants then would be predicted to have low lung volumes. The aim of this study was to test that hypothesis by comparing the lung volumes of infants who had had mild-moderate BPD with those without BPD of similar postmenstrual age. Lung volumes of 17 infants who had mild-moderate BPD (oxygen dependent beyond 28 days, but not past term) (BPD infants) were compared to those of 17 infants without BPD (non-BPD infants). All were born at less than 33 weeks of gestation and studied at postmenstrual ages of 33 to 39 weeks. Lung volume was assessed by measurement of functional residual capacity (FRC). The BPD infants had lower lung volumes (median 19.1 ml/kg) than the non-BPD infants (median 26.5 ml/kg) (p=0.0001). The BPD compared to the non-BPD infants were of greater postnatal age (p=0.0003), born at a lower gestational age (p=0.0001) and of lighter birthweight (p=0.0001). Regression analysis, however, demonstrated that lung volume was significantly related to BPD status (p=0.005), independently of postnatal age, birthweight and gestational age. It is concluded that the lower lung volumes of the infants who had had mild-moderate BPD support the hypothesis that new BPD is associated with poor alveolarisation.     

Alpha-synuclein pathology does not predict extrapyramidal symptoms or dementia

Intracytoplasmic aggregation of alpha-synuclein protein as Lewy bodies in the brainstem neurons is diagnostic for Parkinson's disease, whereas if this process also occurs in the cortical neurons, it is considered pathognomonic for dementia with Lewy bodies. However, the link between alpha-synuclein incorporation into inclusions, neuronal dysfunction, and clinical symptoms needs to be clarified. Another important issue of the pathogenetic puzzle is to understand where alpha-synuclein pathology begins and how it progresses in the brain. To study this, we collected all cases from autopsy material (N = 904) that had alpha-synuclein pathology in the dorsal motor nucleus of vagus, substantia nigra, and/or basal forebrain nuclei. In this way, our study has a unique design because the selection of material is entirely based on the presence of alpha-synuclein pathology regardless of clinical phenotype. Retrospective clinical assessment then showed that only 32 (30%) of 106 alpha-synuclein-positive cases were diagnosed with a neurodegenerative disorder. The distribution or load of alpha-synuclein pathology did not permit a dependable postmortem diagnosis of extrapyramidal symptoms or cognitive impairment. Some neurologically unimpaired cases had a reasonable burden of alpha-synuclein pathology in both brainstem and cortical areas, suggesting that alpha-synuclein-positive structures are not definite markers of neuronal dysfunction.     

Effect of fluoride varnishes on color stability of esthetic restorative materials

Fluoride varnish applications were applied to two hybrid resin composite materials, Z-100 (3M Dental Products, St Paul, MN, USA) and Esthet-X (Dentsply Caulk, Milford, DE, USA), shades A1 and A2 and a glass ionomer, GC Fuji IX GP Fast (GC Corporation, Tokyo, Japan), shade A2, to evaluate color stability. Specimens (12.6-mm dia x 2.3 mm) were prepared using a polyethylene frame, light-cured and polished through a 1-microm alumina finish. After the initial baseline color measurements, the discs were suspended in Fusayama artificial saliva (FAS) solution at 37 degrees C for 48 hours. Post immersion, the specimens were divided into five groups (n=15 each). The following fluoride varnishes were applied to four groups of test specimens: Duraphat (Colgate Oral Pharmaceutical, Inc, Canton MA, USA), Cavity Shield (OMNII Oral Pharmaceuticals, West Palm Beach, FL, USA), Duraflor (Pharmascience Inc, Montreal, Canada) and Fluor Protector (Vivadent, Ivoclar North America, Amherst, NY, USA). The varnish was allowed to dry for five minutes before immersion. The control group was not coated with varnish, although the specimens were immersed in FAS. All specimens were incubated in newly prepared FAS at 37 degrees C for 24 hours, cleaned with an electric toothbrush and the process repeated using newly prepared FAS. CIE L*a*b* color measurements were recorded five times: at baseline, after 48 hours FAS immersion, after cleaning the first and second fluoride varnish applications and after the final brushing using a commercial toothpaste (Crest). A Minolta CR-300 tristimulus colorimeter with an 8-mm aperture (Ramsey, NJ, USA) was used to record color measurements with the daylight (D65) setting. Calculations were performed for using CIE parameters deltaE*, deltaL*, delta a*, delta b*. Analysis of variance (ANOVA) and post-hoc test (Fisher's PLSD) were used for statistical analysis. After immersion in saliva, the tested glass ionomer (Fuji IX) produced the most significant color changes (deltaE*=1.19 and deltaL*=-1.03), indicating the effect of the color change was due to absorption. After fluoride varnish applications, Duraphat varnish produced significant changes in all tested materials and shades, resulting in color changes with deltaE greater than (>) 1 but less than (<) 3. These color changes are considered visually perceptible, yet have been reported in dental literature as clinically acceptable. Fluoride varnishes can be used without adversely affecting the color of restorative materials.