Collagen-induced arthritis in C57BL/6 (H-2b) mice: new insights into an important disease model of rheumatoid arthritis

Collagen-induced arthritis (CIA) is a widely used model of rheumatoid arthritis (RA) and has been important for understanding autoimmunity. CIA is purportedly restricted to mice bearing the MHC class II H-2q or H-2r haplotypes. In this study, we re-examined established concepts regarding susceptibility to CIA. We found mice derived from the C57BU6 (B6) (H-2b) background can develop CIA with high incidence (60-70%), and sustained severity by using an immunization procedure modified for optimum response in DBA/1 (D1) (H-2q) mice. Clinically and histologically the B6 disease resembles that of D1 mice and is dependent on immunization with type II collagen, as well as on B and CD4+ T cells. In contrast, 129/Sv mice, which share H-2b, are resistant to CIA. We conclude that susceptibility to CIA may reflect immunization conditions and/or important contributions from non-MHC genes, revealed by different immunization protocols. A practical outcome is that CIA can be directly applied to gene knockout mice generated from B6 embryonic stem cells without need for backcross onto the D1 background. This model may lead to improved understanding of autoimmunity in CIA and RA and may provide a platform for analysis of the contribution of non-MHC genes to CIA.     

Depressive symptoms predict medical care utilization in a population-based sample

BACKGROUND: Several examinations have detected a relation between depressive symptoms and medical utilization. However, selection biases have been involved in most previous examinations. We sought to test the association between depressive symptoms and prospective, increased medical care utilization, in a population-based Canadian sample, while controlling for utilization due to medical illness and controlling for selection bias. METHODS: Data from the Nova Scotia Health Survey 1995, an age- and sex-stratified random sampling of 3227 Nova Scotian adults, included the Center for Epidemiological Studies-Depression scale and items assessing chronic medical conditions and current limitations in daily activities resulting from medical illness. We linked survey data with medical care utilization measures for the year following the survey, including out-patient visits, reimbursement for out-patient services, hospitalizations, and hospitalization days. RESULTS: After controlling for age, sex, count of medical diagnoses and current medical severity, those with a greater level of depressive symptoms were at greater risk of having increased medical care utilization in the following year. These results remained after removing mental health care utilization costs. CONCLUSIONS: In a population-based sample, depressive symptoms predicted greater medical care utilization, independent of a number of medical severity measures. Whether depressive symptoms are a risk marker or a causal risk factor for increased medical utilization remains to be explored.     

Influences on prescribing in non-fundholding general practices.

BACKGROUND: The experience from general practice fundholding suggests that financial incentives may influence prescribing; guidelines and hospital prescribing are two other suggested influences. AIM: A study was undertaken to establish general practitioners' attitudes to a financial prescribing incentive scheme, the presence and use of guidelines, and the influence of prescribing initiated within secondary care. METHOD: A postal questionnaire survey of non-fundholding general practices in the former Northern Region was conducted. RESULTS: Practices' thinking and subsequent decisions about the incentive prescribing scheme were most often influenced by discussions within the practice (45%). Those practices that achieved their savings under the incentive scheme were less likely than those not achieving savings to feel that the target was not achievable, the time scale was unacceptable, and that the philosophy behind the scheme was unacceptable. Forty-five per cent of practices received advice from neither a medical nor a pharmaceutical adviser; 27% of practices received advice from both, 12% from a medical adviser only and 16% from a pharmaceutical adviser only. Of the practices that tried to make their target savings, 91% intended to increase generic prescribing; fewer than one-third of practices mentioned any other measure. Prescribing guidelines were reported by a minority of practices, although reported rates of use were high when these were present. Clinical guidelines for three conditions, asthma, diabetes and hypertension, were present in more than 50% of practices; 25% of practices had no clinical guidelines. Hospital prescribing was reported as 'always' or 'usually' influencing prescribing for diabetes by 57% of respondents, ischaemic heart disease by 55%, peptic ulceration by 49%, asthma by 42% and hypertension by 39%. CONCLUSIONS: General practitioner prescribing is influenced by a complex web of factors, with no single factor pre-eminent. To understand this area further, there is a need to take each of these areas and ascertain the match between doctors' perceptions and actual practice.     

Concurrent de novo interstitial deletion of band 2p22 and reciprocal translocation (3;7)(p21;q22).

A child is described with a de novo interstitial deletion of band 2p22 and a reciprocal translocation (3;7)(p21;q22). The child has mild developmental delay, coloboma of the right eye, and Hirschsprung's disease. The clinical and cytogenetic findings are described.     

Serological studies on chemostat-grown cultures of Lactobacillus fermentum and Lactobacillus plantarum.

Lactobacillus fermentum NCTC 6991 and Lactobacillus plantarum NCIB 7220 were grown in a chemostat in the diffusible fraction of complex medium at pH 6.0 with glucose limitation. Organisms grown at different dilution rates (D) were injected into rabbits, and the resultant antisera were examined for reactivity with antigens previously isolated from batch-grown organisms. For L. fermentum, antisera obtained on injecting cells grown at D = 0.5 h-1 contained a significantly higher level of antibody reacting with lipoteichoic acid and a lower level of antibody reacting with wall polysaccharide than did antisera obtained with slower-growing cells (D = 0.05 and 0.033). Antibodies to the cell wall polysaccharide were alpha-D-glucosyl specific and cross-reacted with dextran and alpha-D-glucosyl ribitol teichoic acid from L. plantarum. The immunogenicity of the ribitol teichoic acid and lipoteichoic acid components of L. plantarum was not influenced by injecting organisms grown at different rates. However, chemical and serological studies indicate that growth of L. plantarum in the diffusible fraction of complex medium results in a wall teichoic acid of lower glucose substitution. This apparently influences the specificity of the resultant antibodies so that some sera react much less with glucosyl-substituted lipoteichoic acid and dextran.     

Rapid detection of vancomycin-resistant enterococci.

Campylobacter blood agar with clindamycin incubated in 6% CO2 served as a medium to both screen for vancomycin resistance and select for presumptive enterococci. Colonies that grew on the medium were specifically identified as enterococci within 30 min by the pyroglutamyl-beta-naphthylamide and rapid bile esculin tests. The combination of a selective medium plus rapid enzyme substrate tests offered an inexpensive means to enumerate vancomycin-resistant enterococci from specimens by using readily available reagents.     

Prosthetic hip joint infection due to Campylobacter fetus.

A case of postoperative prosthetic hip joint infection due to Campylobacter fetus subsp. fetus is described. Difficulties in isolation and antimicrobial susceptibility testing of this organism are discussed.     

Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors.

BACKGROUND. The idiotypic determinants of the surface immunoglobulin of a B-cell lymphoma can serve as a clonal tumor-specific marker, which may have implications for immunotherapy. We sought to determine whether idiotype-specific immune responses against this autologous antigen could be induced in patients with B-cell lymphoma. METHODS. Nine patients were selected who had minimal residual disease or a complete remission after chemotherapy. Each received a series of subcutaneous injections of the immunoglobulin derived from his or her tumor cells (immunoglobulin-idiotype protein), which had been conjugated to a protein carrier and mixed with an immunologic adjuvant. RESULTS. In seven of the nine patients the injections induced sustained idiotype-specific immunologic responses of the humoral type (two patients), the cell-mediated type (four patients), or both (one patient). The use of an adjuvant was essential for these immune responses. The induced antibodies bound specifically to autologous immunoglobulin idiotype, inhibited the binding of murine monoclonal antiidiotype antibodies, and bound autologous tumor cells. Cell-mediated responses were demonstrated by the specific proliferation of immune peripheral-blood mononuclear cells to the soluble immunoglobulin-idiotype protein in vitro. The tumors of both of the patients with measurable disease regressed completely. Toxicity associated with the vaccine was minimal and consisted only of mild reactions at the site of intramuscular injection. CONCLUSIONS. These results demonstrate that autologous immunoglobulin idiotype can be formulated into an immunogenic, tumor-specific antigen in humans with B-cell lymphoma, and they provide the background for large-scale trials of active specific immunotherapy of this disease.