Smoking and disease severity in rheumatoid arthritis: association with polymorphism at the glutathione S-transferase M1 locus

OBJECTIVE: To determine whether the relationship between smoking and disease severity in women with rheumatoid arthritis (RA) is associated with polymorphism at the glutathione S-transferase (GST) M1 locus. METHODS: Genotyping for GSTM1 was carried out using polymerase chain reaction methodology on 164 women with established RA. Smoking history was obtained on each patient. Radiographic damage was measured by the Larsen score, and functional outcome was assessed by the Health Assessment Questionnaire (HAQ). Data were analyzed by multiple regression analyses, with correction for age and disease duration. RESULTS: Ever having smoked was associated with a worse radiographic and functional outcome than was never having smoked. Both past and current smoking were associated with increased disease severity. Stratification by GSTM1 status revealed that polymorphism at this locus affected the relationship between smoking and disease outcome measures. Patients who lacked the GSTM1 gene and had ever smoked had significantly higher Larsen and HAQ scores than did those who lacked the gene and had never smoked. Radiographic outcome in these patients was worse than that in patients who had the GSTM1 gene and who had smoked. The associations were not affected by correction for socioeconomic status. Rheumatoid factor (RF) production was found to be associated with smoking in only the GSTM1-null patients. CONCLUSION: Our data suggest that disease outcome in female RA patients with a history of smoking is significantly worse than in those who have never smoked. Smoking was associated with the most severe disease in patients who carried the GSTM1-null polymorphism. This association may be due in part to a relationship between the GSTM1 polymorphism and RF production in smokers.     

Rapid identification of donor and recipient cells after allogeneic bone marrow transplantation using specific genetic markers

The fate of the donor graft in allogeneic bone marrow transplantation, the presence of chimaerism and early relapse can be monitored by identification of the donor or recipient origin of haemopoietic cells in peripheral blood and bone marrow. We have done this by the use of highly informative locus-specific hypervariable DNA probes in two sex and blood group matched transplants. In four sex mismatched transplants the Y chromosome was identified by in situ hybridization using a biotinylated Y probe. Early engraftment by day 13 was detected in five of the six patients. Transient chimaerism occurred in half of the cases and was accompanied by the temporary appearance of the Philadelphia chromosome in one patient with chronic myeloid leukaemia without subsequent relapse. Persistence of the graft in the face of falling peripheral counts was documented in four of the six patients studied. The morphology as well as origin of the haemopoietic cells could be characterized by the Y probe analysis. In one patient, recipient lymphocytes were shown to co-exist with myeloid series of donor origin. We conclude that both techniques are highly specific, sensitive and can provide information within 24-48 h. Thus they are of value in guiding early therapeutic intervention in allogeneic transplantation.     

The strength of primary care in Europe: an international comparative study

Background

A suitable definition of primary care to capture the variety of prevailing international organisation and service-delivery models is lacking.

Aim

Evaluation of strength of primary care in Europe.

Design and setting

International comparative cross-sectional study performed in 2009–2010, involving 27 EU member states, plus Iceland, Norway, Switzerland, and Turkey.

Method

Outcome measures covered three dimensions of primary care structure: primary care governance, economic conditions of primary care, and primary care workforce development; and four dimensions of primary care service-delivery process: accessibility, comprehensiveness, continuity, and coordination of primary care. The primary care dimensions were operationalised by a total of 77 indicators for which data were collected in 31 countries. Data sources included national and international literature, governmental publications, statistical databases, and experts’ consultations.

Results

Countries with relatively strong primary care are Belgium, Denmark, Estonia, Finland, Lithuania, the Netherlands, Portugal, Slovenia, Spain, and the UK. Countries either have many primary care policies and regulations in place, combined with good financial coverage and resources, and adequate primary care workforce conditions, or have consistently only few of these primary care structures in place. There is no correlation between the access, continuity, coordination, and comprehensiveness of primary care of countries.

Conclusion

Variation is shown in the strength of primary care across Europe, indicating a discrepancy in the responsibility given to primary care in national and international policy initiatives and the needed investments in primary care to solve, for example, future shortages of workforce. Countries are consistent in their primary care focus on all important structure dimensions. Countries need to improve their primary care information infrastructure to facilitate primary care performance management.     

Exploring the functional morphology of the Gorilla shoulder through musculoskeletal modelling

Musculoskeletal computer models allow us to quantitatively relate morphological features to biomechanical performance. In non-human apes, certain morphological features have long been linked to greater arm abduction potential and increased arm-raising performance, compared to humans. Here, we present the first musculoskeletal model of a western lowland gorilla shoulder to test some of these long-standing proposals. Estimates of moment arms and moments of the glenohumeral abductors (deltoid, supraspinatus and infraspinatus muscles) over arm abduction were conducted for the gorilla model and a previously published human shoulder model. Contrary to previous assumptions, we found that overall glenohumeral abduction potential is similar between Gorilla and Homo. However, gorillas differ by maintaining high abduction moment capacity with the arm raised above horizontal. This difference is linked to a disparity in soft tissue properties, indicating that scapular morphological features like a cranially oriented scapular spine and glenoid do not enhance the abductor function of the gorilla glenohumeral muscles. A functional enhancement due to differences in skeletal morphology was only demonstrated in the gorilla supraspinatus muscle. Contrary to earlier ideas linking a more obliquely oriented scapular spine to greater supraspinatus leverage, our results suggest that increased lateral projection of the greater tubercle of the humerus accounts for the greater biomechanical performance in Gorilla. This study enhances our understanding of the evolution of gorilla locomotion, as well as providing greater insight into the general interaction between anatomy, function and locomotor biomechanics.     

Free‐Radical Polymerization of N‐Vinylimidazole and Quaternized Vinylimidazole in Aqueous Solution

Aqueous‐phase free‐radical batch polymerizations of N‐vinylimidazole (NVI) and quaternized N‐vinylimidazole (QVI) are conducted with varying initial monomer and initiator concentrations at 70 and 85 °C. The polymerization rate of NVI is very slow at the natural pH of 9 due to degradative radical addition to monomer. The rates are increased by lowering the pH, wherein the degradative addition to NVI monomer is partially (at pH 4) and completely (at pH 1) hindered, with the polymerization rate matching that of QVI at pH 1. The initial rates of polymerization for both NVI and QVI are independent of temperature. A kinetic model developed in Predici that includes the pH‐dependent side reactions can reasonably represent both QVI and NVI polymerization.

     

Factors associated with injecting risk behaviour among serial community-wide samples of injecting drug users in Glasgow 1990-94: implications for control and prevention of blood-borne viruses

Aims. To examine the association between recipient-sharing of needles and syringes and demographic characteristics, injecting behaviour and needle and syringe exchange utilisation . Design. Self-report data from serial cross-sectional surveys. Setting. Multiple street, needle and syringe exchange and drug treatment sites throughout Glasgow. Participants. 2576 current injecting drug users (IDUs) recruited during 1990–94. Findings. In the multiple logistic regression analysis, a significantly lower level of recipientsharing was associated with respondents who resided within 1 mile of a needle and syringe exchange compared to those who lived further away (adjusted OR 1.3; 95% CI 1.0–1.6), and by IDUs who reported obtaining either 6–15, 16–30, or > 30 sterile needles and syringes in an average week from a needle exchange and/or pharmacist (adjusted ORs 0.55, 0.34, 0.25; 95% CIs 0.3–0.9, 0.2–0.6 and 0.2–0.4, respectively) compared to those who obtained no sterile equipment from these sources. Recipient-sharing of needles and syringes in the previous 6 months reduced significantly between 1990 (43%) and 1991–94 (27–33%) (p < 0.0001); this decline was not explained by needle and syringe exchange utilization, suggesting that additional factors were influencing behavioural change at that time. Conclusion. Our data indicate that improving injectors' convenience of access to exchange facilities and increasing the numbers of sterile needles and syringes available to them is likely to result in further reductions in recipient-sharing, and thus the potential for blood-borne virus transmission, among IDUs.     

Absence of antibodies to cyclic citrullinated peptide in sera of patients with hepatitis C virus infection and cryoglobulinemia

OBJECTIVE: To determine if antibodies to cyclic citrullinated peptide (anti-CCP) are found in chronic hepatitis C virus (HCV) infection. METHODS: Rheumatoid factor (RF) and anti-CCP were measured in sera from 50 patients with HCV infection but without cryoglobulinemia, sera from 29 patients with mixed cryoglobulinemia (including 13 with rheumatic symptoms and 5 with arthritis), and sera from 20 normal blood donors. Anti-CCP was measured by second-generation enzyme-linked immunosorbent assay (ELISA). RESULTS: No sera with elevated anti-CCP were found in patients with HCV infection without cryoglobulinemia, and in that population, the maximum anti-CCP was 10 units, well below the positive cutoff of 20 units. Positive findings on RF testing >13 IU/ml were present in 22 (44%) of the HCV patients, with RF >50 IU/ml in 8 (16%) and a maximum RF of 526 IU/ml. Of the cryoglobulinemia patients, 22 (76%) had positive results on tests for RF, including 18 (62%) with RF >50 IU/ml and a maximum RF of 5,540 IU/ml. Two (6.9%) of the cryoglobulinemia patients had borderline-positive findings on tests for anti-CCP (25 units and 37 units), which were false-positive results caused by nonspecific binding in the ELISA. No association between the RF and the anti-CCP concentrations was found. CONCLUSION: Whereas RF was frequent in patients with HCV infection with and without cryoglobulinemia, anti-CCP was not observed in patients with uncomplicated HCV infection. Borderline-positive anti-CCP results were observed infrequently in patients with mixed cryoglobulinemia and were caused by nonspecific binding to plastic. Measurement of anti-CCP may help in diagnosing RA in patients with chronic HCV infection.