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INTRODUCTION: The ageing population means prescribing for chronic illnesses in older people is expected to rise. Comorbidities and compromised organ function may complicate prescribing and increase medication-related risks. Comorbid depression in older people is highly prevalent and complicates medication prescribing decisions. AIM: To determine the prevalence of potentially inappropriate medication use in a community-dwelling population of older adults with depressive symptoms. METHODS: The medications of 191 community-dwelling older people selected because of depressive symptoms for a randomised trial were reviewed and assessed using the modified version of the Beers' Criteria. The association between inappropriate medication use and various population characteristics was assessed using Chi-square statistics and logistic regression analyses. RESULTS: The mean age was 81 (±4.3) years and 59% were women. The median number of medications used was 6 (range 1-21 medications). The most commonly prescribed potentially inappropriate medications were amitriptyline, dextropropoxyphene, quinine and benzodiazepines. Almost half (49%) of the participants were prescribed at least one potentially inappropriate medication; 29% were considered to suffer significant depressive symptoms (Geriatric Depression Scale ≥5) and no differences were found in the number of inappropriate medications used between those with and without significant depressive symptoms (Chi-square 0.005 p=0.54). DISCUSSION: Potentially inappropriate medication use, as per the modified Beers' Criteria, is very common among community-dwelling older people with depressive symptoms. However, the utility of the Beers' Criteria is lessened by lack of clinical correlation. Ongoing research to examine outcomes related to apparent inappropriate medication use is needed.

To formulate a ‘logic’ for how a single immunoglobulin variable region gene generates antibodies with different antigen specificity and polyreactivity, we analysed chimeric antibodies produced in transgenic mice carrying the germ-line human V3–23 gene, multiple diversity (D) and joining (J) gene segments. Hybridomas producing antibodies encoded by the V3–23 gene in combination with different mouse Vκ genes were obtained by fusion of splenocytes from transgenic mice. All antibodies had human μ-chains and mouse light chains, were multimeric in structure and expressed the human V3–23 gene. Nucleotide sequence analyses of genes encoding the heavy and light chains of 12 antibodies in relation to antigen specificity highlighted the importance of heavy chain variable region CDR3 in determining reactivity with different antigens. However, the results also suggest that non-CDR3 sequences intrinsic to the V3–23 gene itself may be involved in, or determine, the binding of the chimeric antibodies to some of the antigens tested in the current study. [ABSTRACT FROM AUTHOR]

To define mechanisms of sustained activation of synovial B lymphocytes in RA, we studied hybridomas established from the local synovial B cell repertoire of two RA patients for Vκ gene expression and for antigen-binding specificity. The analyses revealed that members of the main Vκ families (I, II and III) were utilized at frequencies consistent with random Vκ gene family use. Furthermore, although the hybridomas expressed genes frequently seen in response to other self- and exogenous antigens, only one VκI- and two of three VκIII-expressing hybridomas exhibited reactivity with self-antigens. Nucleotide sequence analysis revealed that all hybridomas, with the exception of rheumatoid factor (RF)-producing hybridomas, expressed Vκ genes highly related to known germ-line genes (99.3–100% homology)and that diversity was generated by deletions and random nucleotide insertions at the Vκ-Jκ junction. Examination of the few nucleotide changes seen within the Vκ genes revealed a predominance of silent to replacement changes. Moreover, most of these changes can be attributable either to allotypic variations or to limited random nucleotide replacements independent of antigen selection. In contrast, one IgG-RF (B4DS) exhibited predominantly replacement nucleotide changes in the complementarity-determining regions, suggestive of antigen-driven selection. The random expression of immunoglobulin variable region genes with no, or little, evidence of mutation in the synovial B lymphocyte repertoire, including natural polyreactive antibodies, alongside mutated IgG-RF, suggest that both polyclonal activation and antigen-driven responses occur in RA synovia. [ABSTRACT FROM AUTHOR]

Hip fracture incidence has shown strong upward secular trends in many societies with wide differences in age adjusted incidence between nations. Falls and reduced physical activity have emerged as the strongest risk factors in epidemiological studies, while clinical investigations have pointed to secondary hyperparathyroidism as an important candidate cause of the loss of femoral cortical bone in old age. Until recently there have been few studies performed directly on the region of interest in the proximal femur. Non-invasive methodology using 85Sr has now been developed by our group for measuring bone formation and (with concurrent serial DXA densitometry) resorption in the femoral neck. Bone turnover averaged about 8% annually in controls. A group of younger cases of femoral fracture showed similar indices of total and regional bone formation to a control group; but their resorption was higher. To further investigate this, a femoral neck bone biopsy technique has been developed which can be applied to fracture cases treated by arthroplasty. Preliminary studies have established that the anatomical asymmetry of the neck in cross-section is considerable and imposes restraints on the interpretation of smaller or incomplete femur biopsies. Prospects are quite good that, in the absence of tetracycline pre-labeling, mineralization can be studied by assessment of alkaline phosphatase-positive surfaces in cryostat sections. Moreover, such sections will permit study of other anatomically localized metabolic activities as well as antigen expression and osteocyte viability. Candidate mechanisms for the regional decline in bone quality as well as bone mass in subjects suffering hip fracture can now be investigated more effectively. [ABSTRACT FROM AUTHOR]

The genetic restriction and specificity of the immune response in mice to two fusion proteins, ZZ-M3 and ZZ-M5, were studied. These proteins contain two IgG-binding domains (ZZ) from staphylococcal protein A, and repeated sequences from the C-terminal [(VEHDAEEN)5 (VEEN)10] (M3) or central [(VEEPTVADDEH)3(VEEPTVAEEH)2] (M5) regions of the Plasmodium falciparum malaria blood stage antigen Pf155/RESA. Strong antibody and T-cell responses to M3 and M5 were linked to expression of the I-Ak allele, and T-cell responses to the bacterial fusion partner ZZ were restricted to mice of the H-2k haplotype. The response to MS was less restricted than that to M3, giving intermediate responses in mice of H-2b and H-2d haplotypes as well. However, ZZ-M5-primed lymph node (LN) cells from these mice were primarily induced to proliferate In vitro by the complete ZZ-M5 construct and not by synthetic peptides representing the repeated subunits in M5. The reactivity with intact Pf155/RESA in erythrocyte membrane immunofluorescence was weak of antisera from mice immunized with ZZ-M5, whereas the reactivity of antisera from mice immunized with ZZ-M3 roughly paralleled their reactivity with M3 in an enzyme-linked immunosorbent assay (ELISA). The antibody responses induced by immunization with ZZ-M3 or ZZ-M5 were specific for M3 or M5, respectively, while activated T cells displayed cross-reactivity between M3 and M5 in an in vitro proliferation assay. The results indicate that the assembly of repeated sequences in fusion proteins affects both the MHC class II restriction and the specificity of the induced antibody and T-cell responses. [ABSTRACT FROM AUTHOR]