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Biomedical subjects

Christine A Clark

Publications and source records attributed to Christine A Clark.

4 recordsLinked to original sources

Differential regulation of EP receptor isoforms during chondrogenesis and chondrocyte maturation.

Regulation of chondrogenesis and chondrocyte maturation by prostaglandins has been a topic of interest during recent years. Particular focus on this area derives from the realization that inhibition of prostaglandin synthesis with non-steroidal anti-inflammatory drugs could impact these cartilage-related processes which are important in skeletal development and are recapitulated during bone healing either post-trauma or post-surgery. In addition to reviewing the relevant literature focused on prostaglandin synthesis and signaling through the G-protein coupled EP receptors, we present novel findings that establish the expression profile of EP receptors in chondroprogenitors and chondrocytes. Further, we begin to examine the signaling that may be involved with the transduction of PGE2 effects in these cells. Our findings suggest that EP2 and EP4 receptor activation of cAMP metabolism may represent a central axis of events that facilitate the impact of PGE2 on the processes of mesenchymal stem cell commitment to chondrogenesis and ultimate chondrocyte maturation.

Aging↗

Antiphospholipid syndrome in systemic lupus erythematosus: is the whole greater than the sum of its parts?

This article compares the manifestations of systemic lupus erythematosus (SLE) in the presence and absence of antiphospholipid antibodies (aPLs), the hallmark autoantibodies of antiphospholipid syndrome (APS). The combination of SLE and APS appears to be of greater concern than either entity alone. APS complicates SLE by adding a vaso-occlusive factor to the inflammatory component that adversely affects the prognosis of those who have lupus and aPLs. The increase in both morbidity and mortality when both are present has significant therapeutic implications. Anticoagulation may be a safer and more appropriate therapeutic option than instituting a regimen of corticosteroids and immunosuppressive agents with all their attendant adverse effects. It falls upon the physician to clearly define the disease entity and fully evaluate the disease process.

Antibodies, Antiphospholipid↗

Decrease in pregnancy loss rates in patients with systemic lupus erythematosus over a 40-year period.

OBJECTIVE: To determine if there has been a statistically significant change in pregnancy loss and preterm delivery rates in patients with systemic lupus erythematosus (SLE). METHODS: We analyzed the pregnancy outcomes of our SLE patients over the past 3 years and reviewed the literature over the past 40 years. We extracted pregnancy loss and preterm delivery data from reports of postdiagnosis SLE pregnancies. Studies were grouped into 5-year periods and weighted according to sample size. Group means, calculated for each study period, were plotted using linear regression to determine significance, and compared with population norms for the same periods. RESULTS: The rate of loss in SLE pregnancies over the past 40 years decreased from a mean of 43% in 1960-1965 to 17% in 2000-2003 (r2 = 0.648). This approximates the pregnancy loss rate in the general US population. Preterm deliveries were not uniformly reported and were rarely stratified into spontaneous or physician-initiated. Prior to 1980, it was not possible to derive group means for each time period. From 1980 to 2002, however, there was a trend toward a decrease in preterm births in SLE pregnancies, although they continue to be more frequent in SLE than in the general population. CONCLUSION: Improvements in disease management and perinatal monitoring have resulted in a significant decrease in pregnancy loss in SLE over the last 40 years and a trend toward decreased preterm deliveries over the last 20 years in comparison to the general population. These advances highlight the importance of collaboration between rheumatologists and perinatologists. Given these data, the description of SLE-associated pregnancy could be revised to reflect a more positive prognosis for mother and fetus.

Abortion, Spontaneous↗

Preterm deliveries in women with systemic lupus erythematosus.

OBJECTIVE: To compare the clinical, laboratory, and demographic variables of women in our clinic with systemic lupus erythematosus (SLE) who have had a pregnancy resulting in a live birth and identify any correlations with either term or preterm delivery. METHODS: Pregnancies in women with SLE from 1999 to 2001 were retrospectively reviewed. We recorded demographic data, disease activity (SLE Disease Activity Index, SLEDAI), obstetric history, prednisone dosage, other medications taken during pregnancy, history of renal disease, and autoantibody status [including antinuclear antibody, anti-DNA, anticardiolipin IgG (aCL), and lupus anticoagulant (LAC)]. Preterm delivery was defined as gestational age at delivery < 37 weeks. We performed a literature survey using PubMed and the key words SLE, pregnancy, and outcome. RESULTS: Of the 72 pregnancies, 28 (38.9%) resulted in preterm deliveries. There were no significant differences in any demographic or disease variables measured comparing term versus preterm delivery groups. More women in the preterm group were taking > or = 10 mg/day prednisone during their pregnancy (50.0% vs 22.2%; p = 0.028), and the mean dose was significantly higher than the term group taking > or = 10 mg/day (24.8 vs 16.7 mg/day; p = 0.047). There was a higher prevalence of women with aCL IgG in the preterm group (p = 0.023). The mean weeks gestation was shorter for women positive for aCL IgG compared to the group negative for aCL (34.9 +/- 4.4 vs 37.5 +/- 3.2 weeks, respectively; p = 0.032). There was no difference in second trimester disease activity between the term and preterm groups (33.3% and 36.4% of each group had a SLEDAI of 0). However, significantly more women in the term group received no medication during their pregnancies compared to women in the preterm group (20.0% vs 0.0%; p = 0.031). CONCLUSION: The rates of preterm deliveries, premature rupture of membranes, intrauterine growth restriction, and aPL in SLE pregnancies vary considerably in published reports, most of which are retrospective analyses. Our rates closely approximate the median values for all measures. We found preterm deliveries to be associated with disease activity (as determined by the use of any medication throughout pregnancy vs no medication, and prednisone dose > or = 10 mg/day) and the presence of aCL IgG but not LAC. Our results suggest that inactive disease rather than controlled disease at the onset of pregnancy may be the determining factor in extending SLE pregnancies to full term, thereby decreasing maternal and fetal morbidity.

Anti-Inflammatory Agents↗