Elevated cerebrospinal fluid sphingomyelin levels in prodromal Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, but still without known disease mechanism, proper treatment and efficient diagnostic tools for an early stage diagnosis. There is increasing evidence that lipids, especially cholesterol and sphingolipids, may play a role in pathological processes that occur in the AD brain even in very early stages of the disease. However, lipid changes in cerebrospinal fluid (CSF) of individuals with AD have not been well studied. In previous work, we developed a reproducible and sensitive nano-HPLC-MS method for CSF phospholipids screening and conducted a pilot study to find potential phospholipid changes in CSF from individuals with AD dementia. We observed a slight increase (24%) of sphingomyelin (SM) in CSF samples from patients with probable AD compared to non-demented controls. The goal of this work was to validate our findings and to analyze how SM CSF levels change in different stages of AD from prodromal to mild and moderate AD. We found significantly increased SM levels (50.4±11.2%, p=0.003) in the CSF from individuals with prodromal AD compared to cognitively normal controls, but no change in CSF SM levels between mild and moderate AD groups and cognitively normal controls. These results suggest that alterations in the SM metabolism may contribute to early pathological processes leading to AD.

Nano-HPLC-MS analysis of phospholipids in cerebrospinal fluid of Alzheimer's disease patients--a pilot study.

There is emerging evidence that lipids play an important role in many neurodegenerative processes, for example in Alzheimer's disease (AD). Although different lipid alterations in the AD brain have been reported, there have only been very few investigations of lipid changes in the cerebrospinal fluid (CSF). Recent developments in mass spectrometry (MS) have enabled fast and sensitive detection of lipid species in different biological matrixes. In this study we developed an on-line HPLC-MS method for phospholipid profiling in the CSF based on nano-HPLC separation using an Amide column and detection with electrospray (ESI) quadrupole-time of flight (QTOF) MS. We achieved good separation, reproducibility, and sensitivity in monitoring of the major phospholipid classes, phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), and sphingomyelin (SM) in CSF. To emphasize the applicability of the method, a pilot study was performed on a group of CSF samples (N = 16) from individuals with probable AD and non-demented controls. We observed a statistically significant increase of SM levels (24.3 ± 2.4%) in CSF from probable AD individuals vs. controls. Our findings indicate that SM levels in the CSF could potentially provide a new lead in AD biomarker research, and show the potential of the method for disease-associated CSF phospholipid screening.

Prevalence of epilepsy in Croatia: a population-based survey.

OBJECTIVES: To investigate the prevalence of active epilepsy in Croatia. MATERIAL AND METHODS: Patient data collected by means of questionnaires completed by primary healthcare physicians; epilepsy was previously confirmed in the patients by neurologists or neuropaediatricans. RESULTS: One hundred and twenty-seven of 180 (71%) physicians provided the requested information. The total sample was 212 069 people and of these 1022 had active epilepsy. Prevalence rates (per 1000) for the following age-groups were: age 0-7: 3.5; age 8-18: 6.4; age 19-45: 5.0; age 46-65: 4.7; age >65: 4.4. The age-adjusted prevalence rates for the standard populations were 4.9/1000 (European population) and 5.0/1000 (WHO world population). Fifty-one physicians (29%) stated only the number of patients they considered as having active epilepsy but without the requested details. If their patients were also included, the estimated crude prevalence rate would be 5.5/1000. CONCLUSIONS: It is likely that the prevalence of active epilepsy in Croatia is between 4.8 and 5.5/1000; this is in keeping with findings from other European countries.

[Scientific and technical publications of the Institute of Medical Research and Occupational Health 1988-1993]. / Znanstvena i strucna publicistika Instituta za Medicinska Istrazivanja i Medicinu Rada od 1988. do 1993.

The bibliographic output of the Institute over an eight-year period (1988-1993) was classified into nine categories: scientific papers published in journals covered by Current Contents, scientific papers covered by other secondary publications, scientific papers in journals not covered by non-selective secondary or tertiary publications, congress communications, congress abstracts, technical papers, chapters in books, books and theses. The number of the Institute's staff, their academic degrees and professions were also recorded. The ratio between the number of papers and the number of scientists was calculated and compared to the ratio in the previous years and in some other research institutions in the country. An increase was observed in the Institute production of scientific papers in international journals. The papers were published in journals covered by all seven Current Contents editions. Most papers were in journals which were covered by the Life Sciences edition of Current Contents.

Epidemiological model of hepatitis B with age structure.

Multistate epidemiological model with age structure is constructed on the grounds of natural history of the hepatitis B. Essential epidemiological classes constitute the basis of the model. Epidemiological parameters and the coefficients of transfer among the classes were determined from available information. Uncertainty of infectiousness of some classes of the population was an important constraint in model formulation. Population structure, the distribution of epidemiological classes and other parametric values were rather arbitrarily set but these can be changed as more accurate information becomes available. As new information on natural history may become available this can be incorporated into the present model, with appropriate modifications of its structure. The computer program+ of the model has been written in BASIC language, and can be accommodated within microcomputers. The model is used for simulation of endemic and epidemic situations. It is applied for simulating the natural course of infection as well as the effects of various public health interventions, such as passive and active immunization and/or application of appropriate sanitary and hygienic measures. The cost-effectiveness analysis of various public health control programmes can also be carried out with the model. The model is evaluated through the simulations of actual and hypothetical situations. The model in its present form, permits simulation of the disease dynamics in various populations and epidemic situations. It seems to be a useful tool in the study of hepatitis B dynamics, its epidemic patterns and in the search for the effective and cost-effective, control strategies.

Impact of hepatitis B immunization strategies on infection rates in Italy: a deterministic computer simulation.

The impact of different immunization strategies on hepatitis B infection rates in Italy over a 20 year period is simulated by the means of a simple deterministic mathematical model. The anticipated effect of vaccination of health workers only, of newborns from HBsAg+ mothers, of all newborns, of the entire population are simulated. Immunization of newborns from HBsAg+ mothers is by far the strategy with the greater effectiveness per unit cost.

Epidemiological model of hepatitis B.

This is a preliminary report on a multistate epidemiological model without age structure constructed on the grounds of the natural history of hepatitis B. In determining twelve essential epidemiological classes and related epidemiological parameters the lack of precise definitions of certain classes and their infectiousness was an important constraint in model formulation. For this reason the distribution of some classes and their parametric values were rather arbitrarily set. As more exact information on natural history becomes available it can be directly incorporated into the present model. The computer programme of the model has been written in basic language. The model was used for the simulation of endemic and epidemic situations. It was applied for simulating the natural course of infection as well as the effects of various public health interventions, such as passive and active immunization and/or application of appropriate sanitary and hygienic measures. The model is evaluated through the above simulations of actual and hypothetical situations. The cost-effectiveness analysis of various public health interventions can also be carried out with the model. The model in its present form, in spite of some uncertainties as far as epidemiological parameters are concerned, seems to be useful in the study of hepatitis B dynamics and its epidemiological patterns and in the search for effective and cost-effective control strategies. The model needs further refinement.