Culture model of human corneal epithelium for prediction of ocular drug absorption.

PURPOSE: The main purpose of this study was to develop a cell culture model of immortalized epithelium from the human cornea for drug permeability testing. METHODS: Immortalized human corneal epithelial (HCE) cells were grown on filters, with various filter materials and coating procedures. In the optimal case, HCE cells were grown on polyester filters coated with rat tail collagen gel containing fibroblast cells. Transepithelial electrical resistance (TER) was measured during the growth of the cells to evaluate the epithelial differentiation and tightness of the epithelial cell layers. Transmission electron microscopy (TEM) was used to show the formation of tight junctions, desmosomes, and microvilli. Cellular morphology was characterized by light microscopy. Permeabilities of (3)H-mannitol and 6-carboxyfluorescein were determined, to evaluate the intercellular spaces of the epithelium. Rhodamine B was used as a lipophilic marker of transcellular permeability. Permeabilities of the excised rabbit corneas were determined in side-by-side diffusion chambers. RESULTS: The TER values of the corneal epithelial cultures were 200 to 800 Omega x cm(2), depending on the culture conditions. In optimal conditions, cultured corneal epithelium consisted of five to eight cell layers, TER was at least 400 Omega x cm(2), and the most apical cells were flat, with tight junctions, microvilli, and desmosomes. The permeability coefficients (P(cell), 10(-6) cm/sec) for (3)H-mannitol, 6-carboxyfluorescein, and rhodamine B were 1.42 +/- 0.36, 0.77 +/- 0.40, and 16.3 +/- 4.0, respectively. Corresponding values (at 10(-6) cm/sec) for the isolated rabbit corneas were 0.38 +/- 0.16, 0.46 +/- 0.27, and 18.1 +/- 4.0, respectively. CONCLUSIONS: The TER, morphology, and permeability of the cultured corneal epithelial cells resemble those of the intact cornea. This cell culture model may be useful in evaluation of corneal drug permeation and its mechanisms.

Implementation of guidelines in primary health care. A challenge for the municipal health centres in Finland.

OBJECTIVE: To assess the implementation of guidelines in Finnish primary health care units. DESIGN: A semi-quantitative analysis of a cross-sectional interview survey. SETTING: All municipal health centres in a selected region in Finland. SUBJECTS: Head physicians and head nurses of the 31 participating units. MAIN OUTCOME MEASURES: Number of guidelines adopted; methods used in the implementation; and the unit's estimated purposefulness in the implementation of guidelines. RESULTS: All health centres had adopted at least one guideline in the defined task areas, but only one-third of the units had implemented several guidelines. The implementation methods utilised were usually directive and passive rather than co-operative and problem-solving. Half of the units used training and methods involving active participation of the personnel, and in one-third a multiprofessional approach was applied. Clients' representatives were hardly ever involved in the adaptation of guidelines. A quarter of the health centres were assessed as purposeful in their policy to implement guidelines, the large units being more goal-oriented than the smaller ones. CONCLUSIONS: A minority of health centres are goal-oriented in the adoption of guidelines and use versatile methods to support the implementation; this presents an important managerial challenge for national health care development in Finland.

How to lead a group--practical principles and experiences of conducting a promotional group in health-related physical activity.

In this article the different roles and styles of instruction for the leader of a promotional group in physical activity are described. The promotional group is defined as one in which group dynamics is used to its maximum in order to facilitate permanent change in the members' health-related physical activities. Thus e.g., the group forms its own goals on the basis of its members' individual needs and aspirations and the group members provide feedback, behavioural models and encouragement to each other in their pursuit of change. The leader-instructor works in a stepwise fashion from assessment to evaluation to reformulation of plans made and monitors closely the stages of adoption of physical activity in his or her group. As the group advances the instructor should be ready to transfer more and more responsibility to the members.

What are groups all about?--basic principles of group work for health-related physical activity.

The basic group processes such as norms, roles, social support, and the developmental phases of a group are defined and applied to physical activity groups. Three kinds of groups are differentiated for the promotion of health-related physical activity: on-the-spot information in groups, traditional physical activity groups, and interactive promotional groups. The case is forwarded that in the promotion of physical activity group work is most effective, if it is based on mutual interaction between the group members and utilizes group processes. Arguments are presented for the advantage of interactive promotional groups to help people adopt health-related physical activities.

Expression of insulin-like growth factor II in female breast cancer as related to established prognostic factors and long-term prognosis.

The expression of insulin-like growth factor II (IGF-II) was analysed immunohistochemically in a series of 211 breast cancers with special reference to standard prognostic factors and patient survival. IGF-II was expressed both in the cancer cells and in stromal cells, in 84% and 50% of cases, respectively. IGF-II expression in cancer cells was related to a non-metastatic disease at diagnosis (p = 0.03), low tumour grade (p = 0.02), DNA diploidy (p = 0.02) and S-phase fraction under 7% (p = 0.001). IGF-II negativity was positively correlated to morphometric SD of nuclear area (p = 0.0003), nuclear perimetry (p = 0.002), SD of nuclear perimetry (p = 0.02), minimum nuclear diameter (p = 0.005) and maximum nuclear diameter (p = 0.003). The expression of IGF-II in stromal cells was related to low histological grade (p = 0.02), mitotic index under 10/mm2 (p = 0.01), mild nuclear pleomorphism (p = 0.03), DNA diploidy (p = 0.08), SD of nuclear area (p = 0.006), mean nuclear perimeter (p = 0.05), minimum nuclear diameter (p = 0.005) and maximum nuclear diameter (p = 0.007) in that the nuclear factor values were higher in tumours without stromal IGF-II expression. In univariate and multivariate survival analysis, immunohisto-chemically detected expression of IGF-II had no independent prognostic value over standard prognostic factors. Despite the fact that expression of IGF-II was inversely related to several histopathological features of malignancy, the clinical behaviour of breast cancer seemed to be independent of IGF-II expression.

Expression of insulin-like growth factor I (IGF-I) in female breast cancer as related to established prognostic factors and long-term prognosis.

The expression of insulin-like growth factor I (IGF-I) was analysed immunohistochemically in a series of 211 breast cancers with special emphasis on its relationship to conventional prognostic factors and long-term prognosis. Altogether, IGF-I was expressed by the tumour cells in 91% of the breast carcinomas, and by stromal cells in 29%. The expression of IGF-I in cancer cells was weakly related to a high proportion of intraductal growth (P = 0.032), distinct tumour margins (P = 0.048) and high S-phase fraction (P = 0.074). In a univariate analysis, IGF-I expression in cancer cells was significantly related to a high survival probability in the entire cohort (P = 0.0144) as well as in the axillary lymph node positive tumours (P = 0.0286). Alternatively, expression of IGF-I in the stromal cells was related to metastasis at the time of diagnosis (P = 0.05), tumour diameter (P = 0.04), DNA ploidy (P = 0.07) and nuclear pleomorphism (P = 0.025), but it was without prognostic significance in a univariate analysis (P > 0.1). In a multivariate analysis, the conventional prognostic factors were superior to IGF-I expression in predicting the disease outcome, albeit expression of IGF-I in tumour stroma showed some independent prognostic significance in axillary lymph node negative tumours. The results suggest that IGF-I expression is related to malignant histopathological features in breast cancer, and expression of IGF-I has independent prognostic significance in the early phases of the disease.