Theory and action for health promotion illustrations from the North Karelia Project.

The North Karelia Project in Finland illustrates the fundamental goals of health promotion. Specific activities of the project serve as examples of how concepts from the social and behavioral sciences can be applied to achieve estimated reductions in predicted risk of disease. The results in North Karelia are not conclusive, but they are encouraging, and the investigations conducted there is an essential reference for future research in health promotion and disease prevention.     

Carotid plaque mast cells associate with atherogenic serum lipids, high grade carotid stenosis and symptomatic carotid artery disease. Results from the helsinki carotid endarterectomy study

OBJECTIVE: Increased numbers of mast cells (MCs) are present in ruptured coronary plaques, suggesting to play a role in acute coronary syndromes. We evaluated the distribution densities of MCs, macrophages and T cells in carotid plaques and correlated these findings to stroke risk factors as well as history of stroke or TIA. METHODS AND RESULTS: Seventy-eight carotid samples from 75 patients (16 plaques from asymptomatic patients and 62 from patients with recent ischemic symptoms) undergoing carotid endarterectomy with an internal carotid stenosis >70% that were immunostained and quantified for MCs, macrophages and T cells. The MC distribution density showed positive correlation with the degree of carotid stenosis (p = 0.012), serum levels of total cholesterol (p = 0.021), LDL cholesterol (p = 0.013) and triglycerides (p = 0.005), and an inverse correlation with serum HDL cholesterol levels (p = 0.001). The average MC density (p = 0.023), but not the macrophage (p = 0.58) or T cell (p = 0.74) density, was higher in the symptomatic than in the asymptomatic patients. In a comparison of plaques ipsilateral and contralateral to the thromboembolic event, the densities of the three types of inflammatory cells were similar. CONCLUSIONS: Increased MC distribution density is associated with an atherogenic serum lipid profile, high-grade carotid artery stenosis and symptomatic carotid artery disease. These findings suggest a potential involvement of MCs in the pathophysiology of carotid artery stenosis.     

Mineralization of dentin induced by treatment with bioactive glass S53P4 in vitro

Dentin hypersensitivity can be managed to occlude dentin tubules, but none of the agents used are components of natural dentin. Using a calcium phosphate precipitation (CPP) method, dentin tubules can be occluded with a calcium phosphate (CaP) layer similar to the major inorganic component of dentin. The CPP method utilizes acidic pH conditions, such as etching of dentin, over the course of several dental treatments. A gentler method can be used to produce a CaP layer on the surface of dentin. By treating with bioactive glass S53P4 (BAG), or regular commercial glass (CG), mineralization occurs in physiologically neutral solutions such as simulated body fluid (SBF) and remineralization solution (RMS). After a short period of immersion, silica is dissolved from both types of glass, but the amount of silica released is much greater from BAG than from CG. The dissolved silica is adsorbed on the surface of dentin during the pretreatment procedure and enhances the mineralization of dentin in SBF. After 14 days' mineralization the dentin is fully covered by the CaP layer, but after 14 days' immersion in RMS decalcification of the dentin occurs. Pretreatment with BAG decreases the degree of decalcification of dentin during the mineralization process. These findings suggest that bioactive glass S53P4 can be used as a therapeutic material for mineralization of dentin and its tubules in a physiological environment.     

Survival of AA and ANA rats during lifelong ethanol exposure

BACKGROUND: Study of the long-term effects of chronic alcohol consumption in human populations is confounded by genetic and environmental factors. METHODS: The study was intended to investigate the effects on morbidity and survival of lifetime forced ethanol consumption in male and female AA (Alko, Alcohol) and ANA (Alko, Non-Alcohol) rats. The ethanol-exposed rats had 12% ethanol as the only available fluid from 3 to 24 months of age. The control groups had water. Rats that died during the experiment and those that were killed at 24 months of age were all autopsied, and the pathologic findings were recorded. RESULTS: Lifelong ethanol consumption did not change the survival rate of the rats, and had no significant effect on the rates of any of the pathologic measures in either the AA or ANA line of rats, suggesting that this may not be a good animal model for studying the detrimental effects of chronic alcohol. An unexpected, highly significant finding was observed: the AA rats, bred for high voluntary ethanol drinking, lived much longer than the ANA rats, bred for ethanol avoidance. The death rate by 24 months in the AA line was less than one-third of that in the ANA line. This difference was found regardless of whether the animals were maintained on alcohol or water, and in both genders. The AA rats had significantly lower rates of kidney disease, benign tumors, and cardiovascular disease than the ANA animals. CONCLUSIONS: Lifelong ethanol consumption increased neither the mortality nor the morbidity of AA and ANA line of rats. Genes selected in the development of the high drinking AA line have additional effects producing rats that are healthier and living longer than the ANA rats possessing genes resulting in alcohol avoidance.     

Albumin-coated tympanostomy tubes: prospective, double-blind clinical study

OBJECTIVES: Coating an implant with albumin prevents adhesion of proteins, bacteria, and platelets and thus may lead to its improved and prolonged function. Previously, we have demonstrated the inhibition of binding of fibronectin, one of the most adhesive glycoproteins, on human serum albumin (HSA)-coated tympanostomy tubes and the durability of this binding inhibition in a 8-month trial. We have also demonstrated that the HSA coating inhibits the binding of Staphylococcus aureus and Pseudomonas aeruginosa to titanium plates. This prospective study evaluated the effect of albumin coating on tympanostomy tube sequelae and on the outcome of tympanostomized patients. STUDY DESIGN: Double-blind, prospective, randomized clinical trial. METHODS: Two otolaryngological centers in southern Finland enrolled 179 pediatric patients. Number of tube occlusions and otorrhea and tube ventilation time in the ears with HSA-coated titanium tympanostomy tubes were compared with the contralateral ear with its uncoated, otherwise identical titanium tube during a 9-month follow-up period. RESULTS: In HSA-coated tubes, average ventilation time was slightly longer and the number of early tube occlusions significantly less (P < .05). Moreover, in patients with perioperative bleeding, the coating prolonged average ventilation time of tympanostomy tubes significantly (P < .05). CONCLUSIONS: HSA coating reduces early tube occlusions by preventing adherence of blood and secretion.     

Electromagnetic function of polymicrogyric cortex in congenital bilateral perisylvian syndrome

BACKGROUND: Congenital bilateral perisylvian syndrome (CBPS) is characterised by bilateral perisylvian polymicrogyria and suprabulbar paresis. Mild tetraparesis, cognitive impairment, and epilepsy are frequently associated. Sensory deficits are surprisingly rare, even though polymicrogyria often extends to auditory and sensorimotor cortex. OBJECTIVES: To study the sensorimotor and auditory cortex function and location in CBPS patients. METHODS: We mapped the sensory and motor cortex function onto brain magnetic resonance images in six CBPS patients and seven control subjects using sources of somatosensory and auditory evoked magnetic fields, and of rhythmic magnetoencephalographic (MEG) activity phase-locked to surface electromyogram (EMG) during voluntary hand muscle contraction. RESULTS: MEG-EMG coherence in CBPS patients varied from normal (if normal central sulcus anatomy) to absent, and could occur at abnormally low frequency. Coherent MEG activity was generated at the central sulcus or in the polymicrogyric frontoparietal cortex. Somatosensory and auditory evoked responses were preserved and also originated within the polymicrogyric cortex, but the locations of some source components could be grossly shifted. CONCLUSION: Plastic changes of sensory and motor cortex location suggest disturbed cortex organisation in CBPS patients. Because the polymicrogyric cortex of CBPS patients may embed normal functions in unexpected locations, functional mapping should be considered before brain surgery.     

Perceived health as a predictor of early retirement

OBJECTIVES: This study examined the association between perceived health and early retirement. METHODS: A cohort of 1748 men aged 42 to 60 years from eastern Finland was followed from 1984 to 2000. At baseline, the participants had answered a questionnaire regarding their general (as measured by physician diagnoses) and perceived health status. Comprehensive pension records were obtained from the Social Insurance Institution of Finland and the Central Pension Security Institute. The risk of disability pensioning in various disease categories and nonillness-based early pensioning was analyzed using Cox regression modeling. RESULTS: Over 11 years, 855 (48.9%) men received a disability pension, and 331 (18.9%) received a nonillness-based early pension. Only 273 (15.6%) received an old age pension, without previous early pensioning. At the end of the follow-up, 289 (16.5%) were still working. After adjustment for potential confounders, men with poor perceived health at baseline had a relative risk of 2.37 [95% confidence interval (95% CI) 1.79-3.13] for disability pensioning and the highest risk of disability was due to mental illness (RR 3.84, 95% CI 1.86-7.92), followed by musculoskeletal disorders and cardiovascular diseases. The relative risk of receiving a nonillness-based pension was 2.94 (95% CI 1.92-4.50) for this group. CONCLUSIONS: Self-assessed poor health is a strong predictor of early retirement due to mental disorders, musculoskeletal disorders, and cardiovascular diseases. Moreover, the risk of retirement on a nonillness-based pension is increased among those with poor perceived health.     

Cancer cells as targets for lentivirus-mediated gene transfer and gene therapy

Lentiviruses have been used as gene transfer vectors for almost 10 years and their utility has been demonstrated in a variety of different applications. However, their value in cancer gene therapy has not been studied thoroughly. Here we show that VSV-G pseudotyped HIV-1-based lentiviruses are efficient vectors for human tumor cells in vitro and in vivo. Lentiviral gene transfer efficiency was demonstrated by transducing 42 different cell lines, representing 10 different human tumor types. It was shown that most of the cell lines were good or excellent targets for lentiviral transduction, allowing 50-95% gene transfer efficiency. These results were comparable to those obtained with an E1/E3 deleted, serotype 5 adenovirus vector. Analysis of lentivirus vector structure revealed that virus particles devoid of HIV-1 accessory proteins appeared to be more efficient, but the presence of enhancing elements cPPT and WPRE did not play a major role in transduction efficiency to four different human tumor cell lines. However, their effect on the gene expression level in these cells was apparent. To examine the impact of lentiviral gene expression level on suicide gene therapy approach, human osteosarcoma cells were transduced with lentivirus- or adenovirus vectors carrying the fusion gene HSV-TK-GFP and exposed to ganciclovir. Cell viability analysis after the treatment revealed that both vector types induced similar level of cytotoxicity, suggesting that lentiviral expression of a suicide gene is adequate for tumor cell destruction. Finally, in vivo transduction studies with subcutaneous tumors showed that lentivirus vectors can yield similar gene transfer efficiency than adenovirus vector, despite three orders of magnitude lower titer of the lentiviral preparation. In conclusion, these data show that lentiviruses are efficient gene transfer vehicles for human tumor cells and justify their use in further preclinical cancer gene therapy studies.