1
384 SPO Abstracts 312 ELEVATED THROMBOMODULIN (TMI LEVELS IN SEVERE PREECLAMPSIA C.D. Hsu, B. Iriye" T.R.B. Johnson, S.F. Hong', D.W. Chan', Dept. Gyn/Ob and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD. OBJECTIVE: Preeclampsia is a disorder of unknown etiology and pathogenesis. Endothelial cell injury has been suggested. Since TM is a specific cell surface receptor of the vascular endothelial cell, measurement of soluble form of serum TM might serve 8S 8 potential marker of endothelial cell damage in preeclampsia. STUDY DESIGN: Thirty-four pregnant women with preeclampsia were matched with 34 normotensive women with singleton pregnancies in the third trimester. Subjects were matched for maternal age, gestational age, parity and race. Among these 34 subjects, 20 had mild preeclampsia and 14 had severe preeclampsia defined by ACOG criteria. Soluble serum TM was determined by 8 two-site enzyme- linked immunosorbent assay (Diagnostics Stago,Asnieres,France). Paired-comparisons t- test was used for statistical analysis. RESULTS: The mean ± SEM of serum TM level in 32 patients with preeclampsia was 13.93± 1.26 ng/ml and 9.99±0.61 ng/ml in matched controls (P = 0.0091. Serum TM levels between patients with severe preeclampsia and matched controls were significantly different (17.88 ± 2.26 vs. 9.26 ± 0.83 ng/ml; P = 0.00281. However, there was no significant difference between patients with mild preeclampsia and matched controls (11.17 ± 1.13 vs. 10.61 ± 0.86 ng/ml; P =0.6403). CONCLUSIONS: (11 Serum TM level is elevated in patients with preeclampsia. (21 Serum TM level is significantly higher in patients with severe preeclampsia, but not in patients with mild preeclampsia compared to matched controls. (31 Elevated TM levels in patients with severe preeclampsia may reflect a more severe vascular endothelial injury. (41 Serum TM levels may serve as a marker for this serious complication of pregnancy. 3 13 ELEVATED SERUM HUMAN CHORIONIC GONADOTROPIN AND ITS SUBUNITS LEVELS IN SEVERE PREECLAMPSIA C.D. Hsu, D.W. Chan', B. Iriye', T.R.B. Johnson, S.F. Hong', B.D. Weintraub: J.T. Repke, Dept. Gyn/Ob and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD. OBJECTIVE: Preeclampsia is a trophoblastic disorder. Human chorionic gonadotropin (hCGI is produced by trophoblastic tissue. Therefore, We sought to determine whether measurement of hCG levels (total, a, and P subunitsl may serve as a useful marker to predict the severity of preeclampsia. STUDY DESIGN: Twenty patients with mild preeclampsia and 12 with severe preeclampsia defined by ACOG criteria were matched with 32 healthy normotensive women with singleton pregnancies in the third trimester. Serum levels of total and p-hCG were measured by a two-site immunoenzymometric assay (Tosoh, San Francisco, California) and a- hCG was determined by a double antibody radioimmunoassay (Weintraub, NIH; Hazleton, Virginial. Pair-comparisons t test was used for statistical analysis. RESULTS: Serum levels of total-hCG, a-hCG, and p-hCG subunits were significantly higher in severe preeclamptic women (p< 0.061, but not in mild preeclamptic group, as compared with those in their matched controls. Among these three markers, the best predictor for severe preeclamptic women was serum levels of a-hCG. With a cutoff value of 700 ng/ml, serum a-hCG predicted severe preeclampsia with a sensitivity of 76%, specificity of 83%, positive predicted value of 82%, and negative predicted value of 77%. CONCLUSIONS: Our data revealed that serum hCG and its subunits levels are significantly elevated in patients with severe preeclampsia, but not with mild preeclampsia. Furthermore, serum a-hCG levels may serve as a better marker in severe preeclampsia. January 1993 Am J Obstet Gynecol 314 ABNORMAL INSULIN RECEPTOR TYROSINE KINASE ACfIVITY (IRTKA) IN ERYTHROCYTE MEMBRANES FROM WOMEN WITH PREECLAMPSIA. L.L. Simpson x , D.B. Jacobs x , RJ. Sokol, J.R. Sowers x . Wayne State University School of Medicine, Detroit Michigan. OBJECflVE: We and others have demonstrated that insulin resistance is present in preeclamptic pregnancies. In order to further investigate the nature of the insulin resistance we have evaluated erythrocyte membrane IRTKA at term in African- American women with preeclampsia as compared to controls. STUDY DESIGN: Nulliparous women were defmed as preeclamptic if their diastolic blood pressure was greater than 100 mm Hg and they had proteinuria greater than 1 +. Briefly, partially purified solubilized insulin receptors were prepared by lectin affinity chromatography from erythrocyte membranes. IRTKA was determined in these receptors by phosphorylation of an exogenous substrate (Glu80-ryr2<). RESULTS: There was no difference in the two groups in specific insulin binding to solubilized insulin receptors from erythrocyte membranes, or in the EDso (half-maximal stimulation) for IRTKA in these preparations as determined by phosphorylation of (Glu8Orr<) substrate. However, 100nM-insulin-stimulated (maximal minus basal) IRTKA in preeclamptic was greater than in controls (54.7±18.2, n=8 vs. 1.24±O.3 pmoI 32 P/Glu80ryr20/min/mg protein, n=7, p<O.04). CONCLUSION: The data suggest that the insulin signal transduction pathway, as assessed by IRTKA, is altered in nulliparous preeclamptic women. 315 PATHOPHYSIOLOGY OF HYPOCALCIURIA IN PREECLAMPSIA: ISOTOPIC MEASUREMENT OF CALCIUM ABSORPTION L Sanchez-Ramos. A Tolaymat! AL Yergey! N Viera! SA Abrams! V. Calventi! P Edelstein! I Oelke, CD Adair. x Department Obstetrics and Gynecology, University of Florida, Jacksonville, FL. National Institutes of Health, Section on Metabolic Analysis and Mass Spectrometry, Bethesda, MD. CNRC, Baylor College of Medicine, Houston, TX. OBJECTIVE: Some have suggested that hypocalciuria in preeclampsia is due to decreased intestinal absorption of calcium. The aim of this study was to analyze calcium absorption using stable isotopes in patients with preeclampsia and in normotensive controls. STUDY DESIGN: Fifteen pregnant subjects were studied; 8 with preeclampsia (hypertension and proteinuria) and 7 normotensive controls. All patients were on their normal diet and had a 24-hour recall performed by a dietician. The subjects received two stable calcium isotopic tracers. An oral tracer (44Ca 0.04 mg/Kg) was given with milk, while an intravenous tracer (42Ca 1.0 mg/Kg) was infused over 7-10 minutes. Calcium concentration was determined by atomic absorption spectrophotometry and isotope ratios by thermal ionization mass spectrometry from pooled 24-hour urine samples. RESULTS: Preliminary results show no difference in absorption between preeclamptic and normotensive control patients. The mean absorption for preeclamptics was 0.282±..051 and 0.306±..079 for normotensive controls. (p=.49) However, the fraction of dietary calcium appearing in the urine differed significantly (.060 for preeclamptics and .087 lor normotensive controls. P=.008) CONCLUSIONS: In spite of the indirect evidence of others, calcium absorption does not appear to be impaired in patients with preeclampsia. The retention site of the unexcreted calcium is at present unidentified.

312 Elevated Thrombomodulin ITM) Levels in Severe Preeclampsia

Embed Size (px)

Citation preview

Page 1: 312 Elevated Thrombomodulin ITM) Levels in Severe Preeclampsia

384 SPO Abstracts

312 ELEVATED THROMBOMODULIN (TMI LEVELS IN SEVERE PREECLAMPSIA C.D. Hsu, B. Iriye" T.R.B. Johnson, S.F. Hong', D.W. Chan', Dept. Gyn/Ob and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD. OBJECTIVE: Preeclampsia is a disorder of unknown etiology and pathogenesis. Endothelial cell injury has been suggested. Since TM is a specific cell surface receptor of the vascular endothelial cell, measurement of soluble form of serum TM might serve 8S 8 potential marker of endothelial cell damage in preeclampsia. STUDY DESIGN: Thirty-four pregnant women with preeclampsia were matched with 34 normotensive women with singleton pregnancies in the third trimester. Subjects were matched for maternal age, gestational age, parity and race. Among these 34 subjects, 20 had mild preeclampsia and 14 had severe preeclampsia defined by ACOG criteria. Soluble serum TM was determined by 8 two-site enzyme­linked immunosorbent assay (Diagnostics Stago,Asnieres,France). Paired-comparisons t- test was used for statistical analysis. RESULTS: The mean ± SEM of serum TM level in 32 patients with preeclampsia was 13.93± 1.26 ng/ml and 9.99±0.61 ng/ml in matched controls (P = 0.0091. Serum TM levels between patients with severe preeclampsia and matched controls were significantly different (17.88 ± 2.26 vs. 9.26 ± 0.83 ng/ml; P = 0.00281. However, there was no significant difference between patients with mild preeclampsia and matched controls (11.17 ± 1.13 vs. 10.61 ± 0.86 ng/ml; P =0.6403). CONCLUSIONS: (11 Serum TM level is elevated in patients with preeclampsia. (21 Serum TM level is significantly higher in patients with severe preeclampsia, but not in patients with mild preeclampsia compared to matched controls. (31 Elevated TM levels in patients with severe preeclampsia may reflect a more severe vascular endothelial injury. (41 Serum TM levels may serve as a marker for this serious complication of pregnancy.

3 13 ELEVATED SERUM HUMAN CHORIONIC GONADOTROPIN AND ITS SUBUNITS LEVELS IN SEVERE PREECLAMPSIA C.D. Hsu, D.W. Chan', B. Iriye', T.R.B. Johnson, S.F. Hong', B.D. Weintraub: J.T. Repke, Dept. Gyn/Ob and Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD. OBJECTIVE: Preeclampsia is a trophoblastic disorder. Human chorionic gonadotropin (hCGI is produced by trophoblastic tissue. Therefore, We sought to determine whether measurement of hCG levels (total, a, and P subunitsl may serve as a useful marker to predict the severity of preeclampsia. STUDY DESIGN: Twenty patients with mild preeclampsia and 12 with severe preeclampsia defined by ACOG criteria were matched with 32 healthy normotensive women with singleton pregnancies in the third trimester. Serum levels of total and p-hCG were measured by a two-site immunoenzymometric assay (Tosoh, San Francisco, California) and a­hCG was determined by a double antibody radioimmunoassay (Weintraub, NIH; Hazleton, Virginial. Pair-comparisons t test was used for statistical analysis. RESULTS: Serum levels of total-hCG, a-hCG, and p-hCG subunits were significantly higher in severe preeclamptic women (p< 0.061, but not in mild preeclamptic group, as compared with those in their matched controls. Among these three markers, the best predictor for severe preeclamptic women was serum levels of a-hCG. With a cutoff value of 700 ng/ml, serum a-hCG predicted severe preeclampsia with a sensitivity of 76%, specificity of 83%, positive predicted value of 82%, and negative predicted value of 77%. CONCLUSIONS: Our data revealed that serum hCG and its subunits levels are significantly elevated in patients with severe preeclampsia, but not with mild preeclampsia. Furthermore, serum a-hCG levels may serve as a better marker in severe preeclampsia.

January 1993 Am J Obstet Gynecol

314 ABNORMAL INSULIN RECEPTOR TYROSINE KINASE ACfIVITY (IRTKA) IN ERYTHROCYTE MEMBRANES FROM WOMEN WITH PREECLAMPSIA. L.L. Simpsonx

,

D.B. Jacobsx, RJ. Sokol, J.R. Sowersx. Wayne State University School of Medicine, Detroit Michigan. OBJECflVE: We and others have demonstrated that insulin resistance is present in preeclamptic pregnancies. In order to further investigate the nature of the insulin resistance we have evaluated erythrocyte membrane IRTKA at term in African­American women with preeclampsia as compared to controls. STUDY DESIGN: Nulliparous women were defmed as preeclamptic if their diastolic blood pressure was greater than 100 mm Hg and they had proteinuria greater than 1 + . Briefly, partially purified solubilized insulin receptors were prepared by lectin affinity chromatography from erythrocyte membranes. IRTKA was determined in these receptors by phosphorylation of an exogenous substrate (Glu80-ryr2<). RESULTS: There was no difference in the two groups in specific insulin binding to solubilized insulin receptors from erythrocyte membranes, or in the EDso (half-maximal stimulation) for IRTKA in these preparations as determined by phosphorylation of (Glu8Orr<) substrate. However, 100nM-insulin-stimulated (maximal minus basal) IRTKA in preeclamptic was greater than in controls (54.7±18.2, n=8 vs. 1.24±O.3 pmoI32P/Glu80ryr20/min/mg protein, n=7, p<O.04). CONCLUSION: The data suggest that the insulin signal transduction pathway, as assessed by IRTKA, is altered in nulliparous preeclamptic women.

315 PATHOPHYSIOLOGY OF HYPOCALCIURIA IN PREECLAMPSIA: ISOTOPIC MEASUREMENT OF CALCIUM ABSORPTION L Sanchez-Ramos. A Tolaymat! AL Yergey! N Viera! SA Abrams! V. Calventi! P Edelstein! I Oelke, CD Adair. x Department Obstetrics and Gynecology, University of Florida, Jacksonville, FL. National Institutes of Health, Section on Metabolic Analysis and Mass Spectrometry, Bethesda, MD. CNRC, Baylor College of Medicine, Houston, TX. OBJECTIVE: Some have suggested that hypocalciuria in preeclampsia is due to decreased intestinal absorption of calcium. The aim of this study was to analyze calcium absorption using stable isotopes in patients with preeclampsia and in normotensive controls. STUDY DESIGN: Fifteen pregnant subjects were studied; 8 with preeclampsia (hypertension and proteinuria) and 7 normotensive controls. All patients were on their normal diet and had a 24-hour recall performed by a dietician. The subjects received two stable calcium isotopic tracers. An oral tracer (44Ca 0.04 mg/Kg) was given with milk, while an intravenous tracer (42Ca 1.0 mg/Kg) was infused over 7-10 minutes. Calcium concentration was determined by atomic absorption spectrophotometry and isotope ratios by thermal ionization mass spectrometry from pooled 24-hour urine samples. RESULTS: Preliminary results show no difference in absorption between preeclamptic and normotensive control patients. The mean absorption for preeclamptics was 0.282±..051 and 0.306±..079 for normotensive controls. (p=.49) However, the fraction of dietary calcium appearing in the urine differed significantly (.060 for preeclamptics and .087 lor normotensive controls. P=.008) CONCLUSIONS: In spite of the indirect evidence of others, calcium absorption does not appear to be impaired in patients with preeclampsia. The retention site of the unexcreted calcium is at present unidentified.