To evaluate whether serum relaxin (S-relaxin) can predict spontaneous delivery before 34 weeks of gestation in high risk pregnancies.
A prospective cohort study.
Calculated sample size was reached ...over a two-year period, during which 9507 women gave birth. Of these, 157 healthy women were eligible for the study as they were admitted with symptoms of delivery before 34 weeks of gestation. Ninety-three women were included. Overall participation rate was 59%.
Healthy women with singleton pregnancies with symptoms of delivery before 34 weeks of gestation.
S-relaxin was measured using a standard sandwich ELISA.
End points were preterm delivery before 34 weeks of gestation and delivery within three days from initiation of symptoms. The best possible prediction of preterm delivery was established using logistic regression for risk factors individually associated with preterm delivery before 34 weeks of gestation. S-relaxin was dichotomised to obtain best possible fit and then entered into the model. The same analyses were done for delivery within three days.
Median S-relaxin levels varied significantly in the women with preterm prelabour rupture of membranes (PPROM) (316 pg/mL), contractions (222 pg/mL) or ripe cervices (203 pg/mL) (
P < 0.05). S-relaxin above the 80th centile (≥300 pg/mL) was associated with an increased risk of preterm delivery crude OR = 4.8; (95% CI: 1.9–12). Likelihood ratio of a positive test is 2.6 (1.5–4.9) and S-relaxin resulted in a post-test probability of preterm delivery of 0.72, compared with a pre-test probability of 0.49. S-relaxin contributed to the identification of delivery within three days adj. OR = 11 (95% CI: 1.8–64).
S-relaxin may be a useful predictor in women with symptoms of delivery before 34 weeks of gestation.
Objective
To evaluate whether serum relaxin (S‐relaxin) can predict spontaneous delivery before 34 weeks of gestation in high risk pregnancies.
Design
A prospective cohort study.
Setting
Calculated ...sample size was reached over a two‐year period, during which 9507 women gave birth. Of these, 157 healthy women were eligible for the study as they were admitted with symptoms of delivery before 34 weeks of gestation. Ninety‐three women were included. Overall participation rate was 59%.
Population
Healthy women with singleton pregnancies with symptoms of delivery before 34 weeks of gestation.
Methods
S‐relaxin was measured using a standard sandwich ELISA.
Main outcome measures
End points were preterm delivery before 34 weeks of gestation and delivery within three days from initiation of symptoms. The best possible prediction of preterm delivery was established using logistic regression for risk factors individually associated with preterm delivery before 34 weeks of gestation. S‐relaxin was dichotomised to obtain best possible fit and then entered into the model. The same analyses were done for delivery within three days.
Results
Median S‐relaxin levels varied significantly in the women with preterm prelabour rupture of membranes (PPROM) (316 pg/mL), contractions (222 pg/mL) or ripe cervices (203 pg/mL) (P < 0.05). S‐relaxin above the 80th centile (≥300 pg/mL) was associated with an increased risk of preterm delivery crude OR = 4.8; (95% CI: 1.9–12). Likelihood ratio of a positive test is 2.6 (1.5–4.9) and S‐relaxin resulted in a post‐test probability of preterm delivery of 0.72, compared with a pre‐test probability of 0.49. S‐relaxin contributed to the identification of delivery within three days adj. OR = 11 (95% CI: 1.8–64).
Conclusion
S‐relaxin may be a useful predictor in women with symptoms of delivery before 34 weeks of gestation.
Bone sialoprotein (BSP) is a phosphorylated skeletal glycoprotein. Here we describe a new procedure for the purification of BSP involving wide-pore reversed-phase HPLC, and the development of a ...homologous RIA for human BSP. The immunoassay showed linearity between 3 and 120 micrograms/L, a lower detection limit of 0.7 micrograms/L, and a mean recovery rate of 99.4%. Intraassay variation was 7.0% (mean = 10.9 micrograms/L) and 6.1% (mean = 38.8 micrograms/L), and interassay variation was 9.2% (mean = 11.1 micrograms/L) and 9.4% (mean = 39.0 micrograms/L). No cross-reactivity was detected with osteocalcin, osteonectin, or bone alkaline phosphatase. Preliminary clinical evaluation in healthy controls (n = 90) showed a mean serum BSP concentration on 12.1 +/- 5.0 micrograms/L (+/- SD). BSP was significantly increased in patients with Paget disease of bone, primary and secondary hyperparathyroidism, and also in subjects with renal failure without skeletal involvement. Impairment of hepatic function did not affect serum BSP concentrations.
Bone sialoprotein (BS), a protein synthesized by osteoblasts and osteoclasts and highly modified posttranslationally, constitutes a predominant fraction of the noncollagenous organic matrix in human ...bone. We report an assessment of serum concentrations of BS in patients with malignant bone diseases. In patients with bone metastases (according to scintigraphic criteria), serum BS concentrations were greater than in patients without bone metastases (P <0.05). However, ROC curve analysis revealed that serum BS was inferior to serum bone alkaline phosphatase in discriminating between patients with and without bone metastases. Patients with bone metastases showed a weak correlation between serum BS concentrations and bone formation markers. Only "traditional" markers of bone formation-but not BS-were correlated with urinary deoxypyridinoline (P <0.01). Liver and kidney dysfunction had no significant influence on BS values in these patients (as assessed by analysis of variance; P >0.05). In multiple myeloma patients treated with corticosteroids and bisphosphonates, BS concentrations were lower than in tumor patients without bone metastases (P <0.001), and the correlation between BS concentrations and the number of bisphosphonate courses applied was significant (r = -0.578; P <0.05). In postmenopausal women, serum BS concentrations averaged 142% greater than in premenopausal women. Further studies should be done, therefore, to elucidate whether serum BS is able to predict high bone turnover after menopause.
Bone sialoprotein (BSP), a phosphorylated and sulphated glycoprotein that is expressed by mineralized connective tissues is also produced in tumors that metastasize to bone. To facilitate studies of ...BSP expression in normal and pathological human tissues a monoclonal antibody (BSP 1.2 mab) was raised against human bone BSP. BSP 1.2 mab was shown by ELISA assays to recognize the epitope "DEYSY" (amino acids 279-283) that is conserved in mammalian BSP sequences. However, whereas the antibody recognized recombinant BSPs expressed in bacteria, it did not recognize native forms of rat or pig BSP in which the first tyrosine of the DEYSY peptide sequence appears to be modified. Immunostaining of embryonic human tibiae and calvariae with BSP 1.2 mab showed strong reaction in osteoblasts and osteocytes with relatively weak staining of the bone matrix, suggesting that the BSP 1.2 mab epitope is partially masked in the bone matrix. BSP 1.2 mab also stained osteosarcoma cells and normal trophoblastic cells in the placenta in areas of microcrystalline deposits. Cancer cells in primary breast tumors, lymph nodes, and secondary bone metastases from individual patients were stained strongly by BSP 1.2 mab. Although BSP 1.2 mab also stained breast cancer carcinoma cell lines and SaOS2 osteosarcoma cells, biosynthesis of radiolabelled BSP could not be demonstrated in breast cancer cells. Notably, the staining of BSP in the breast cancer cells was diffuse contrasting the punctate staining, typical of secreted proteins, in SaOS2 cells. These studies, therefore, have identified a unique epitope in human BSP recognized by a monoclonal antibody, BSP 1.2 mab, which can be used for the unequivocal identification of BSP in normal and pathological human tissues.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Urodilatin (95-126) (URO) appears to play a major physiologic role in fluid homeostasis and produces major changes when administered intravenously. Here we describe a monospecific, high-affinity ...antiserum against URO with no cross-reactivity (<0.01%) against the structural highly homologous atrial natriuretic peptide 99-126 (ANP-99-126), ANP analogs, and related peptides such as brain natriuretic peptide. A competitive RIA was developed, based on this antiserum. Urine samples with or without ethanol extraction and plasma samples without pretreatment were analyzed by the RIA, which had a detection limit of 10.5 ng/L, a linear measuring range between 10.5 and 1000 ng/L, and recoveries of 93-102% in urine and 90-104% in plasma. The intraassay CVs were 8.2% and 8.1% for urine samples with 269 and 669 ng/L URO; the interassay CV was 9.7% at 839 ng/L. Using this assay, we present URO data for urine from healthy volunteers receiving low and routine sodium diets and from clinical urine specimens; we also present pharmacokinetic data for URO in plasma from patients suffering from bronchial asthma and treated by URO infusion.
Bone sialoprotein (BSP) is a phosphorylated glycoprotein with a M(r) of 70-80 kDa that accounts for approximately 5-10% of the noncollagenous proteins of bone. Due to its relatively restricted ...distribution to mineralized tissues, BSP may serve as a potential marker of bone metabolism. Employing a recently developed RIA, serum BSP was measured in 133 healthy subjects, aged 20-80 yr, and in patients with primary hyperparathyroidism (pHPT; n = 26), Paget's disease of bone (PD; n = 14), untreated multiple myeloma (MM; n = 32), and breast cancer with bone metastases (BC; n = 19). Results were compared to clinical and laboratory data, including serum total alkaline phosphatase as a marker of bone formation, and the urinary cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone resorption. In healthy adults, serum BSP values ranged between 5.0-21.6 ng/mL (5-95% interval), with a median of 10.5 ng/mL (total group). In healthy females, a linear correlation was found between serum BSP and age (r = 0.51; P < 0.001), with significantly higher values in postmenopausal than in premenopausal women (13.3 +/- 4.8 vs. 9.0 +/- 3.8; P < 0.01). In the healthy group, BSP values did not change with body mass index, lumbar bone mineral density, serum calcium, serum creatinine, or serum total alkaline phosphatase levels. In contrast, a weak, but significant, correlation was observed between serum BSP and the urinary excretion of PYD and DPD. Compared to those in healthy controls, serum BSP levels were significantly higher in patients with pHPT, PD, MM, or BC (P < 0.01 for all groups). These differences remained after analyses were adjusted for age and sex. In pHPT, serum BSP levels were closely correlated to urinary PYD and DPD (r = 0.87 and 0.83, respectively; P < 0.01), whereas in PD, no correlation was observed between any of the bone markers. Serum BSP levels were highest in patients with MM, and there was a significant difference between early and advanced stages of the disease (30.2 +/- 8.0 vs. 64.3 +/- 6.8; P < 0.01). In a subgroup of 15 patients with metastatic BC, iv bisphosphonate treatment resulted in a rapid reduction of serum BSP levels to 40% of the baseline values within 4 days of treatment. In conclusion, BSP appears to be a sensitive marker of bone turnover, and the present data suggest that its serum levels predominantly reflect processes related to bone resorption.
Human congestive heart failure is characterized by complex neurohumoral activation associated with the up‐regulation of vasoconstricting and salt‐retaining mediators and the compensatory rise of ...counter‐regulatory hormones. In the present study, we provide the first evidence that relaxin (RLX), known as a pregnancy hormone, represents a potential compensatory mediator in human heart failure: plasma concentrations of RLX and myocardial expression of the two RLX genes (H1 and H2) correlate with the severity of disease and RLX responds to therapy. The failing human heart is a relevant source of circulating RLX peptides, and myocytes as well as interstitial cells produce RLX. Elevation of ventricular filling pressure up‐regulates RLX expression and the hormone acts as a potent inhibitor of endothelin 1, the most powerful vasoconstrictor in heart failure. Furthermore, RLX modulates effects of angiotensin II, another crucial mediator. Our data identify RLX as a new player in human heart failure with potential diagnostic and therapeutic relevance.—Dschietzig, T., Richter, C., Bartsch, C., Laule, M., Armbruster, F. P., Baumann, G., Stangl, K. The pregnancy hormone relaxin is a player in human heart failure. FASEB J. 15, 2187–2195 (2001)
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