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.     

Do online pharmacies fit European internal markets?

The aim of this article is to consider the suitability of online pharmacies into European internal market area. This required considering the models of present online pharmacies in respect to the existing legislation. Data on online pharmacy settings was collected by looking some online pharmacies, which were found by using Goggle search machine with term "online pharmacy" and by studying websites of some well-known online pharmacies. European legislation and policy were studied from European Union's official website. Online drug markets seem to be increasing in popularity for reasons related to their ready availability and cost benefits. Few online pharmacies are based in Europe, yet online markets are worldwide. Community legislation does not stipulate on the legality of online pharmacies on European internal markets. Instead Community legislation offers framework for electronic commerce that could also include online pharmacy practise. National legislation, however, may rule them out either directly or indirectly. Regardless of European internal markets online pharmacies' cross-border operations are particularly complicated. Preliminary ruling from the European Court of Justice concerning one European online pharmacy's cross-border practise is awaited 2003-2004 and will offer some aspects for future.     

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.     

Somatic factors at 8 years of age in children with recurrent use of antibiotics in early infancy

Aim: To examine the influence of recurrent therapy with antibiotics (RTA) in infancy on children's somatic factors at 8 y of age. Methods: Subject selection was based on stratified randomized cluster sampling. Altogether 1287 infants were potential participants in the follow-up study. Children with ≥6 courses of antibiotics (100 children) during their first 18 mo of life and children with no (62%) or ≤2 courses (38%) of antibiotics participated in a clinical examination in a case-control setting (100 matched controls) at the age of 8 y. Results: The children with RTA continued to have more infections and had had more courses of antibiotics compared to controls during the follow-up. There was no clinically significant difference in the somatic and dental status at the age of 8 between the two groups. The parents of the children with RTA reported significantly more often recurrent infections than the parents of the controls.

Conclusions: The children with recurrent therapy with antibiotics in early childhood also continue to be prescribed more antibiotics in later childhood when compared to those who received no or few antibiotics in infancy. However, recurrent infections and medications do not seem to have a marked effect on the somatic and dental status of these children at 8 y of age.     

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.