Objective To describe first-trimester ultrasound diagnosis and management of pregnancies implanted into uterine Cesarean section scars. Methods

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Objective. In many patients with knee osteoarthritis (OA), the disease progresses, and there is loss of cartilage; in others, the disease stabilizes with time. Previous studies have demonstrated that concentrations of serum proteins that reflect joint tissue metabolism can identify knees that will deteriorate, leading to the suggestion that OA disease activity is phasic or cyclical. The aim of the current study was to determine whether longitudinal measurements of one such protein, serum cartilage oligomeric matrix protein (COMP), are related to disease outcome over a 5-year period.Methods. Serum COMP levels were measured by enzyme-linked immunosorbent assay at study entry and every 6 months thereafter in 115 patients with knee pain and OA of mainly the tibiofemoral joint. Cartilage loss was determined from knee radiographs taken at entry and at 24, 36, and 60 months. Disease progression was defined as either a reduction in the tibiofemoral joint space width by at least 2 mm or total knee replacement (TKR) in either knee at followup. COMP concentrations at baseline and the area under the curve (AUC) of measurements obtained over 5 years were compared between progressors and nonprogressors by Student's 2-tailed t-test. The patterns and probability of progression according to TKR or >2 mm of narrowing of the tibiofemoral joint space were analyzed by logistic regression models.Results. The mean ؎ SD ages of the progressors and nonprogressors were 64.2 ؎ 7.8 years and 63.3 ؎ 10.6 years, respectively, and the proportion of females was 51% and 56%, respectively. Of the 37 patients whose OA progressed (22 by TKR and 15 by >2-mm reduction in tibiofemoral joint space), 13 lost cartilage during the first 2 years, and 18 lost cartilage during the last 2 years. The mean ؎ SD serum COMP concentration at baseline was significantly higher in the progressors compared with the nonprogressors (14.12 ؎ 3.39 units/ liter versus 12.62 ؎ 3.25 units/liter; P < 0.036). Serum COMP levels rose significantly after TKR; however, after allowing for the effect of TKR, the AUC/month was significantly higher in the progressors compared with the nonprogressors (12.52 ؎ 2.71 versus 10.82 ؎ 2.71; P < 0.003). Serum COMP concentrations were higher during periods of radiographic progression and identified periods of progression that were nonlinear. Logistic regression analysis showed that on average, a 1-unit increase in serum COMP levels increased the probability of radiographic progression by 15%.Conclusion. The data suggest that serum COMP is related to progressive joint damage in knee OA. The patterns of progression for the early and late progressors are consistent with the hypothesis that knee OA progression is episodic or phasic. Large between-subject variation precludes the use of individual values to predict progression with confidence. However, sequential measurements of serum COMP levels may identify patients whose OA is likely to progress over the next year or two.Osteoarthritis (OA) is a heterogeneous, complex

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The extent of autoreactive T cell repertoire in the normal individual has previously been unclear. Here we demonstrate that T cells from healthy humans can be stimulated by multiple epitopes on a self protein to give primary proliferative responses in vitro. Synthetic 15-mer peptides, corresponding to the sequence of a human red blood cell Rhesus polypeptide, were tested for the ability to stimulate normal T cells. Multiple peptides were found to provoke responses reproducibly, and the proliferation could be blocked consistently by antibodies to HLA-DR, but not -DP or -DQ. T cells from each donor proliferated in response to different patterns of peptides, but this variation in pattern was less marked in individuals with the same HLA-DR type. The responses were comparable in kinetics to those elicited by the non-recall foreign antigen keyhole limpet hemocyanin, and the responding cells are most commonly derived from the CD45RA+ subpopulation, indicating that they had not been activated in vivo. It is considered that T cells are "immunologically ignorant" of many self peptides, presumably because they correspond to cryptic epitopes that are not normally presented in vivo.

The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P ¼ 0.00043; P c ¼ 0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P ¼ 0.0036; P c ¼ 0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P ¼ 0.02), and the protective IL1B-IL1RN haplotype conferred a fivefold reduced risk of OA (P ¼ 0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA.

Objective-Raised serum C reactive protein (CRP) and hyaluronate (HA) concentrations predict the progression of knee osteoarthritis (OA) in the long term but the consistency of these relations with time is unknown. The purpose of this work was therefore to determine if raised CRP and HA at entry and three years before entry (−3 years) predict radiological progression of knee OA in a group of patients between entry and five years. Methods-Knee radiographs from 90 patients with knee OA at entry and five years follow up were assessed for progression of disease over five years. The concentrations of serum CRP and HA were measured at entry (n=90) and also in 40 serum samples available from −3 years. Odds ratios (OR) for predicting progression were calculated by logistic regression. Results-Serum CRP at entry was not predictive of progression between entry and five years (OR 1.12, 95% CI 0.81, 1.55) but serum CRP at −3 years was predictive of progression (OR 1.90, 95% CI 1.01, 3.28). Serum HA concentration at entry predicted progression between entry and five years (OR 2.32, 95% CI 1.16, 4.66). Conclusion-These results are consistent with previous reports relating to HA, and suggest that raised serum CRP reflects events that precede a period of later radiographic progression in knee OA. However, because of the large overlap between groups, the serum CRP or HA concentration are not good predictors of individual patient progression and have a poor sensitivity and specificity.