Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse.

Idiopathic thrombotic thrombocytopenic purpura (TTP) is characterized by frequent recurrences. Effective screening for relapses will enable intervention prior to overt episodes of TTP. The present study used a modified assay to detect ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, 13) activity as low as 0.5%. This analytical improvement permits adequate measurement of ADAMTS13 activity levels in 97% of remission samples used for statistical modelling. ADAMTS13 activity and ADAMTS13 antibody (IgG) were measured in 157 serial samples prospectively collected from 24 TTP patients during periods of clinical remission. These patients were followed-up quarterly for an average of 23 months, during which time nine episodes of TTP relapse occurred among six patients. Finally, logistic regression modelling was used to define the relationship between ADAMTS13 activity levels (0.5-100%) and the probability of TTP relapses. Our data demonstrated that lower ADAMTS13 activity and younger age were significantly associated with higher risk of relapse in the 3 months after specimens were taken. In contrast, ADAMTS13 antibody IgG levels were not predictive of TTP relapses. Identification of low ADAMTS13 activity during clinical remission as a key risk factor for TTP relapses provides a new screening strategy to identify patients who may benefit from prophylactic therapy prior to disease relapses.

Investigation of the relationship between type 2 diabetes and osteoporosis using Bayesian inference.

This study aims to determine the prevalence of Type 2 diabetes in women with osteoporosis and estimate the odds ratio (OR) of osteoporosis in women with Type 2 diabetes using Bayesian inference. This is a case-control study design that looked into prevalence of diabetes among 582 female patients who had normal bone mineral density (BMD) and 598 female patients with osteoporosis. The subjects included women at least 30 yr of age who had their BMD measured in the lumbar spine and femoral neck using dual-energy X-ray absorptiometry at a tertiary referral center in Manila, Philippines. Prevalence of Type 2 diabetes in subjects with osteoporosis is 22.41%, whereas 19.07% of the subjects with normal BMD had diabetes. The odds of developing osteoporosis is 22.54% higher for Type 2 diabetic subjects. Patients with osteoporosis were older than subjects with normal BMD by almost 10 yr. Of the diabetic osteoporotic patients, 44.78% were physically active compared with 20.72% diabetics with normal BMD. Most of the diabetics (60.36%) with normal BMD were obese, whereas majority of diabetic osteoporotics (64.93%) have normal body mass index (BMI). Less than 10% of both diabetic osteoporotics and diabetics with normal BMD have ever undergone hormone replacement therapy. Of the 598 subjects with osteoporosis, 124 (20.74%) had suffered from fragility fractures. When controlling for physical activity and BMI, the odds of developing osteoporosis was 21.73% and 53.89% higher for Type 2 diabetics, respectively. In considering all possible confounders and effect modifiers (age, physical activity, BMI, and hormone replacement therapy) in the model which made use of a diffuse normal prior distribution, the estimate for OR (Model 1) is 0.67. A separate analysis excluding modifiable confounders (Model 2) gave the measure of association an equal likelihood of diabetes being a protective factor or a risk factor. The crude OR indicated that Type 2 diabetes is a risk factor for osteoporosis. However, when identified confounders were included in the model, the direction of the relationship changed. Considering the credible intervals (95% credible interval in both models), the study concluded that diabetes is indeed a protective factor for osteoporosis. Results of the study may have potential limitations. There are sources of bias that have been identified--selection bias where patients included in the study were referred by primary care givers for a specified reason as well as misclassification and recall biases on certain information such as type and duration of physical activity. Diabetes is a protective factor for osteoporosis in this referred population of women. However, with the well-known diabetes-related factors, that is, microvascular complications, visual acuity, and risk for fall, one should still strongly consider assessing and screening for osteoporosis and fracture risk reduction in diabetic patients.

Calcium apatite crystals in synovial fluid rice bodies.

BACKGROUND: Rice bodies can occur in the joints in many rheumatic conditions, but they are most common in rheumatoid arthritis. They are generally believed to occur rarely in patients with osteoarthritis, but one study reported rice bodies with apatite crystals. OBJECTIVE: To report on a series of joint fluids with rice bodies containing apatite clumps and examine their clinical pictures. METHODS: All synovial fluid analysis reports for 10 years were reviewed for rice bodies and eight patients were reported on. A series of patients with a variety of diseases with synovial fluid rice bodies found to contain calcific material is described. All were examined by compensated polarised light and alizarin red stain, and four were examined by electron microscopy. RESULTS: The eight patients all had alizarin red S chunks embedded throughout the rice body. Transmission electron microscopy disclosed the presence of a matrix of collagen, fibrin, and amorphous materials containing typical apatite crystals. Clinical diagnoses, radiographic findings, and leucocyte counts varied, but six of the eight patients had had previous repeated corticosteroid injections into the joints. CONCLUSION: Aggregates of apatites may be more common than previously recognised in rice bodies as they are not routinely sought. Whether they are a result of joint damage or depot steroid injections and whether that might contribute to further joint injury now needs to be investigated.

Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout?

OBJECTIVE: To determine if lowering of serum uric acid (SUA) concentrations below 6 mg/dl or longer duration of lowered SUA will result in depletion of urate crystals from the knee joints and prevent further attacks of gout. METHODS: A prospective study was initiated 10 years ago at Philadelphia VA Medical Center to attempt to maintain SUA levels of patients with crystal proven gout at < 6.0 mg/dl. We recalled all 57 patients who were available during 1999. Patients were divided into 2 groups: Group A, with SUA still > 6 mg/dl, and Group B, with SUA < or = 6 mg/dl. A knee joint aspirate was requested from all asymptomatic Group B patients and many in Group A. Aspirates were examined by polarized light microscopy for identification of crystals. RESULTS: There were no differences between the groups in age, sex, duration of gout, or serum creatinine. Group A (n = 38) had a mean of 6 attacks of gout for the recent year, those with tophi having the most frequent attacks. Among the 16 patients in this group who agreed to knee aspiration, monosodium urate (MSU) crystals were found in 14, although they were asymptomatic at the time. Nineteen patients (Group B) were able to maintain serum urate levels < or = 6 mg/dl for > 12 months. Nearly half of them had no attack of gout for 2 or more years, with a mean of 1 attack in the last year for the whole group. Three patients in whom tophi were found did not have major flares of gout within the past year. Knee joint aspiration was done on 16 asymptomatic patients. Seven (44%) still had MSU crystals present in their knees. Patients in this group who were taking prophylactic colchicine did not differ with respect to the character of synovial fluid from those who had discontinued it for up to several years, although the frequency of attacks was less in those who continued colchicine. CONCLUSION: A majority of patients were able to deplete urate crystal stores in their knee joint fluids when their SUA levels were kept to < or = 6 mg/dl for several years. The mechanisms for persistence in some patients, and whether such crystals have clinical implications, are not known. Patients with chronic gout need serum urate concentrations to be kept low to prevent further attacks.

Invasive tophaceous pseudogout in the temporomandibular joint: misdiagnosis as tumor: case report and review of the literature.

We report a case of focal calcium pyrophosphate dihydrate (CPPD) arthropathy in a 72-year-old, white woman that occurred in the temporomandibular joint (TMJ), a relatively unusual location for CPPD crystals. The patient underwent surgical exploration and radiation therapy because of histologic interpretation of an initial biopsy specimen as showing metastatic poorly differentiated carcinoma. Further evaluation of the specimen revealed the presence of positively birefringent crystals under compensated polarizing light microscopic examination. Previously reported cases of CPPD affecting the TMJ have also shown that this may mimic neoplastic or infectious conditions. Tophaceous pseudogout at the TMJ is a surprisingly common complication of CPPD deposition disease. As in our patient, it can occur without known CPPD at other sites.

Successful use of diltiazem in calcinosis caused by connective tissue disease.

The mechanism for calcinosis in connective tissue disease remains unclear. Various therapies such as warfarin, colchicine, steroids, and bisphosphonates have been tried. However, despite some benefit in early cases, improvement generally is not seen in advanced cases of calcinosis. Several recent studies strongly suggest a favorable response of calcinosis to diltiazem, a calcium channel antagonist. This report concerns two Filipino women, one with dermatomyositis, the other with undifferentiated connective tissue disease, who showed significant reduction of widespread calcinosis after treatment with diltiazem.