In this paper, we describe surface modification of poly( D,L-lactide- co-glycolide) (PLG) microspheres, intended for DNA vaccine application, with two functionalities: a steric stabilizing component, provided by poly(vinyl alcohol) (PVA) and a cationic component, aimed at subsequent DNA surface loading. The cationic functionality arises from polycations, such as PEI, poly( L-lysine), trimethyl chitosan, and (dimethylamino)ethyl methacrylate, introduced into the water phase of classical oil-in-water (o/w) solvent evaporation method of PLG microsphere fabrication. By systematic evaluation of production variables, a system was produced with balanced properties in terms of microsphere size appropriate for uptake by antigen presenting (e.g., dendritic) cells, colloidal stability, and relatively high DNA loading. The polycation (PEI) molecular weight and preparation concentration were both found to increase the surface polycation content and DNA binding capacity; however, they lead to an increased tendency for aggregation, particularly when the microsphere size was decreased. DNA loading of almost 100% efficiency was achieved under optimized conditions in physiologically acceptable buffers, resulting in a surface DNA loading appropriate for vaccine purposes. A further increase in surface DNA loading was however associated with an increase in the particles negative potential, indicating the surface presence of DNA charges not neutralized by the polycation and hence potentially not protected from in vivo enzymatic degradation. The internalization of surface-loaded DNA into the target cells was confirmed by monitoring fluorescent DNA after the microspheres were endocytosed by the cells in culture.

SUMMARYObjectives. To determine the prevalence of lithium therapy in the over-65s in the Cambridge Mental Health Services catchment area, to abtain a pro®le of this group and to ®nd out how well and by whom lithium treatment is being monitored.Methods. A census was carried out of patients over the age of 65 in the Cambridge Mental Health Services catchment area who were on lithium therapy on 1 February 1995. The records of these patients were examined retrospectively for demographic details, details of lithium therapy, information about lithium monitoring and risk factors associated with lithium treatment.Results. One hundred and forty-eight patients were identi®ed representing a point prevalence of 0.27%. GPs carried out lithium monitoring for the majority of this group and 47% had not been seen by a psychiatrist in the 12 months leading up to the census date. Thirty-two per cent of the group were on thyroxine treatment or had raised TSH levels.Conclusions. The prevalence of lithium therapy in this study was greater than the prevalences reported in studies of patients of all ages. Standards of monitoring varied widely and were not always better where psychiatrists monitored the treatment, although psychiatrists were more likely than GPs to monitor renal function. There was a high rate of thyroid dysfunction in the study group.

Objectives. To determine the prevalence of lithium therapy in the over‐65s in the Cambridge Mental Health Services catchment area, to abtain a profile of this group and to find out how well and by whom lithium treatment is being monitored. Methods. A census was carried out of patients over the age of 65 in the Cambridge Mental Health Services catchment area who were on lithium therapy on 1 February 1995. The records of these patients were examined retrospectively for demographic details, details of lithium therapy, information about lithium monitoring and risk factors associated with lithium treatment. Results. One hundred and forty‐eight patients were identified representing a point prevalence of 0·27%. GPs carried out lithium monitoring for the majority of this group and 47% had not been seen by a psychiatrist in the 12 months leading up to the census date. Thirty‐two per cent of the group were on thyroxine treatment or had raised TSH levels. Conclusions. The prevalence of lithium therapy in this study was greater than the prevalences reported in studies of patients of all ages. Standards of monitoring varied widely and were not always better where psychiatrists monitored the treatment, although psychiatrists were more likely than GPs to monitor renal function. There was a high rate of thyroid dysfunction in the study group. © 1998 John Wiley & Sons, Ltd.