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J C Tsibris

Publications and source records attributed to J C Tsibris.

At least 19 recordsLinked to original sources
PubMed2000

Fetal erythropoietin levels in pregnancies complicated by meconium passage: does meconium suggest fetal hypoxia?

OBJECTIVE: We sought to determine whether umbilical cord plasma erythropoietin levels were different in deliveries complicated by meconium passage and to determine whether this response is influenced by gestational age. STUDY DESIGN: Fetal erythropoietin levels were measured in 203 appropriately grown neonates at 37 to 43 weeks of gestation; among those, 70 had passed meconium. RESULTS: Meconium passage in the entire population was associated with elevated fetal erythropoietin levels (68 vs 31 mIU/mL; P <.001). Cord blood gases, pH, base deficit, and PO (2), as well as the 1- and 5-minute Apgar scores, were not different between the meconium and no-meconium groups. Gestational age and birth weights were significantly higher in the meconium group. Stepwise multiple regression analysis with meconium and gestational age used as the independent variables showed both meconium and gestational age to be independently associated with fetal erythropoietin levels (r = 0.356, F = 14.5; meconium, P <.001; gestational age, P <.01). CONCLUSIONS: These results suggest that meconium passage can be associated with chronic fetal hypoxia as demonstrated by elevated fetal erythropoietin levels, independent of gestational age.

Apgar Score↗
PubMed1999

Human uterine leiomyomata express higher levels of peroxisome proliferator-activated receptor gamma, retinoid X receptor alpha, and all-trans retinoic acid than myometrium.

Uterine leiomyomata are the main indication for a hysterectomy in the United States and occur in 25% of women >35 years. Because uterine leiomyomata can form when ovariectomized guinea pigs are exposed to estradiol and retinoic acids, we tested whether human leiomyomata had high levels of retinoic acids and related nuclear receptors. Compared with normal human myometrium, leiomyomata had 3- to 5-fold higher levels of peroxisome proliferator-activated receptor gamma (PPARgamma), retinoid X receptor alpha proteins, and all-trans retinoic acid, but only during the follicular phase of the menstrual cycle. 9-cis Retinoic acid was undetectable in either leiomyomata or myometrium. PPARgamma mRNA levels were lower in leiomyomata than myometrium, but only during the luteal phase of the cycle. A PPARgamma agonist, troglitazone, was given to guinea pigs along with estradiol and all-trans retinoic acid and produced the largest leiomyomata seen to date in this model. By contrast, no tumors formed when troglitazone was given alone or with estradiol or when troglitazone was given with estradiol and 9-cis retinoic acid. New therapies for human leiomyomata may emerge by combining antagonists for PPARgamma and retinoid X receptor alpha with selective estrogen receptor modulators.

Alitretinoin↗
PubMed1999

Modulation of the prostaglandin E receptor: a possible mechanism for infection-induced preterm labor.

OBJECTIVE: To evaluate the modulatory effects of interleukin (IL)-1beta and prostaglandin (PG)E2 on the PGE2 receptor subtype EP1 in amnion cell cultures. METHODS: Amnion cell cultures were incubated in increasing concentrations of (IL)-1beta or PGE2. Cultures were also incubated in high concentrations of IL-1beta and PGE2 in combination. Changes in EP1 receptor levels were evaluated by western and northern blot analysis. Culture fluid PGE2 levels were measured by enzyme-linked immunosorbent assay. RESULTS: EP1 receptor protein levels decreased with increasing levels of PGE2 (r = -0.82, P < .05). EP1 receptor protein (r = 0.95, P < .05), EP1 mRNA (r = 0.95, P < .01), and culture fluid PGE2 levels (P < .01) were all increased after IL-1beta administration. EP1 receptor levels also increased approximately fourfold in response to IL-1beta incubation even in the presence of high agonist (PGE2) concentrations (P < .01). CONCLUSION: The results of this study show that IL-1beta might be involved in infection-induced preterm labor by interfering with the normal regulation of EP1 receptor levels and with the promotion of increased PGE2 production in amnion tissue.

Cells, Cultured↗
PubMed1999

Fetal erythropoietin levels in growth-restricted and appropriately grown neonates with and without abnormal fetal heart rate tracings: a comparison with cord blood gases and Apgar scores.

OBJECTIVE: To determine if umbilical cord plasma erythropoietin (EPO) levels in combination with cord blood gases and Apgar scores can distinguish between subacute and chronic uteroplacental insufficiency. METHODS: A total of 184 neonates delivered between 1993 and 1997 at Tampa General Hospital were studied. Cord plasma EPO levels, cord blood gases, and Apgar scores were determined prospectively and compared in four subgroups that were defined based on the presence or absence of fetal growth restriction (FGR; chronic fetal hypoxia), abnormal fetal heart rate tracings during labor (FHR; subacute/acute fetal hypoxia), or both. RESULTS: Both growth-restricted and appropriately grown newborns with abnormal intrapartum FHR tracing had elevated umbilical cord plasma EPO (183.5 and 135.2 mIU/ml, respectively; normal = 20.7 mIU/ml) and base deficit, whereas pH, Po2, and 1-minute and 5-minute Apgar scores were significantly lower, compared with appropriately grown newborns with a normal intrapartum course. Among newborns with normal heart rate tracings and FGR, the mean plasma EPO levels were elevated (89.5 mIU/ml), whereas the other parameters were not different from normal. CONCLUSION: Our findings suggest that, although cord blood gases and Apgar scores may reflect subacute and acute events, they are not good predictors of chronic uteroplacental insufficiency. The supplemental use of umbilical cord plasma EPO levels may improve our ability to identify chronic uteroplacental insufficiency.

Apgar Score↗
PubMed1998

Effects of raloxifene in a guinea pig model for leiomyomas.

OBJECTIVE: Chronic exposure of oophorectomized guinea pigs to 17beta-estradiol causes leiomyoma formation. Our aims were to determine whether these leiomyomas can become estradiol independent after exposure to estradiol and if raloxifene inhibits leiomyoma growth when given concomitantly with estradiol. STUDY DESIGN: To induce leiomyoma development, 6 oophorectomized animals received two estradiol implants for 140 days. Next, the estradiol implants were replaced with empty implants in 3 animals, whereas the other 3 received 2 new estradiol implants and raloxifene given per os 10 mg/kg per day for 60 days. Tumor size was monitored biweekly by ultrasonography. RESULTS: On estradiol removal, abdominal wall leiomyomas regressed within 15 to 30 days; when estradiol implants were reintroduced, leiomyomas redeveloped. Within 30 days on raloxifene, all abdominal leiomyomas (n = 9) regressed as determined by ultrasonography and verified at laparotomy. Serum raloxifene and estradiol levels were 432 +/- 46 pg/mL and 78 +/- 13 pg/mL (mean +/- SEM, n = 3), respectively, after 60 days of treatment. CONCLUSIONS: Leiomyomas did not become estradiol independent, even after long exposure to estradiol; ultrasonography allowed frequent, noninvasive assessment of leiomyoma size, and raloxifene rapidly regressed leiomyomas in this animal model.

Animals↗
PubMed1998

Umbilical cord plasma erythropoietin levels in pregnancies complicated by maternal smoking.

OBJECTIVE: Our goal was to determine whether maternal smoking was associated with elevated umbilical cord erythropoietin, a marker for chronic hypoxia. STUDY DESIGN: Plasma erythropoietin levels were measured in umbilical cord plasma of 222 newborns. There were 48 mothers who smoked and 174 nonsmokers. RESULTS: When all pregnancies were included, mean cord plasma erythropoietin levels were significantly higher in the smokers (78.0 +/- 15.3 mIU/ml) compared with the nonsmoking group (35.2 +/- 4.0 mIU/ml; p < 0.005). Regression analysis showed a significant positive correlation between the number of cigarettes smoked per day and cord plasma erythropoietin levels (r = 0.26, p < 0.0001). Smoking was associated with a significantly elevated risk (relative risk = 2.6, 95% confidence interval 1.7 to 10.9, p < 0.005) of fetal growth restriction. When pregnancies with fetal growth restriction were excluded from the analysis, the difference between the two groups remained significant (smokers 81.3 +/- 18.6, n = 38; nonsmokers 24.3 +/- 1.4, n = 164; p < 0.03). CONCLUSIONS: These results illustrate that smoking during pregnancy is associated with fetal growth restriction and significantly elevated umbilical cord erythropoietin levels.

Adolescent↗
PubMed1998

Elevated umbilical cord plasma erythropoietin levels in prolonged pregnancies.

OBJECTIVE: To determine if umbilical cord plasma erythropoietin levels are elevated in pregnancies that continue beyond their expected date for delivery. METHODS: Erythropoietin was measured using an enzyme-linked immunosorbent assay in 124 appropriately grown newborns delivered from 37-43 weeks' gestation. Each woman had an uncomplicated labor and delivery course without evidence of fetal stress or meconium. The comparison was made between pregnancies ending at 37-40 weeks' gestation and those at 41-43 weeks' gestation. RESULTS: There was no difference between the two groups in cord blood gases or Apgar scores at 1 and 5 minutes. Cord plasma erythropoietin levels were significantly higher in pregnancies delivered after 41 completed weeks' gestation (41 or more weeks: 48.0+/-7.1 mIU/mL, n=45 versus 37-40 weeks: 26.1+/-4.2 mIU/mL, n=79, P < .001). When compared with pregnancies delivered between 37 and 40 weeks, erythropoietin levels were significantly elevated in pregnancies delivered at either 41, 42, or 43 weeks' gestation. CONCLUSION: In pregnancies reaching 41 weeks and beyond, cord plasma erythropoietin levels are significantly increased, indicating altered fetal oxygenation in some of these pregnancies. These results support the current practice of close fetal surveillance of prolonged pregnancies.

Adult↗
PubMed1998

Are maternal diabetes and preeclampsia independent simulators of fetal erythropoietin production?

To determine if diabetes and preeclampsia are independent stimulators of erythropoietin, distinct from hypoxia, we measured umbilical cord plasma erythropoietin in 239 deliveries from 24 to 40 weeks of gestation. Mean plasma erythropoietin levels were not different between normal, diabetic, and preeclamptic women when all deliveries were analyzed. When infants with suspected intrauterine hypoxia were excluded, the mean erythropoietin level was considerably lower within all three groups but there was no difference among the groups. In suspected hypoxia, the mean fetal erythropoietin was elevated, but there was no difference between control, diabetic, or preeclamptic pregnancies. These results provide further support that hypoxia remains the only known stimulator of erythropoietin production in the fetus.

Erythropoietin↗
PubMed1998

Tumor necrosis factor-alpha upregulates the prostaglandin E2 EP1 receptor subtype and the cyclooxygenase-2 isoform in cultured amnion WISH cells.

Recent studies have demonstrated a strong correlation between infection and preterm labor. Preterm delivery is also associated with high levels of cytokines and prostaglandins in amniotic fluid. The purpose of this study was to investigate the effect of tumor necrosis factor-alpha (TNF-alpha) on the levels of cyclooxygenase, prostaglandin E2 production (PGE2), and expression of the PGE2 receptor subtype EP1 in amnion WISH cell culture. Amnion WISH cell cultures were incubated in increasing concentrations of TNF-alpha (0-50 ng/ml). Changes in cyclooxygenase and EP1 receptor proteins were evaluated by Western blot analysis. Changes in EP1 mRNA were evaluated by Northern blot, and culture fluid concentrations of PGE2 were estimated by enzyme immunoassay (EIA). EP1 protein (p<0.01), EP1 mRNA (p<0.05), cyclooxygenase-2 (COX-2) protein (p<0.001), and PGE2 concentrations (p<0.01) all increased with increasing concentrations of TNF-alpha. Changes in COX-1 protein were not observed following TNF-alpha-incubation. The results suggest that TNF-alpha may play a role in infection-induced preterm labor by its pleiotropic ability to simultaneously stimulate COX-2 activity, PGE2 concentrations, and PGE2 EP1 receptor levels in human amnion.

Amnion↗
PubMed1997

The effect of interleukin-1 beta and interleukin-4 on the expression of prostaglandin receptors EP1 and EP3 in amnion WISH cells.

PROBLEM: Although prostaglandin E2 (PGE2) is believed to modulate biochemical and immunological events leading to parturition, the role of prostaglandin E receptors during labor has not been investigated. METHOD OF STUDY: Amnion WISH cells were incubated in media containing increasing concentrations of either interleukin-1 beta (IL-1 beta) or IL-4. Increased EP1 and EP3 protein expression was determined by Western blot analysis with peptide-specific antibodies. Concomitant measurements of culture media PGE2 were made by an enzyme immunoassay. RESULTS: Incubation of WISH cells with IL-1 beta or IL-4 caused a two- to three-fold increase in EP1 protein levels. IL-1 beta and IL-4 also caused six- and two-fold increases, respectively, in culture fluid PGE2 concentrations. IL-1 beta or IL-4 had no effect on EP3 protein levels. CONCLUSIONS: Based on these results, it is proposed that IL-1 beta and IL-4 may be involved in the initiation and promotion of labor by inducing EP1 levels and PGE2 production in amnion.

Amnion↗
PubMed1996

Umbilical plasma erythropoietin correlations with blood gases and gestational age in appropriately grown infants.

Erythropoietin (EPO) levels were measured using an ELISA method in umbilical cord plasma from 68 appropriately grown neonates at 27 to 43 weeks of gestation (EGA). A consistent but small (5%) difference was found between the EPO levels in the umbilical artery (Ua), 21.0 +/- 2.5 mlU/mL (mean +/- SEM), and umbilical vein (Uv), 22.0 +/- 2.7 mlU/mL (p < 0.02, n = 30). Significant inverse correlations were found between Ua EPO levels and pO2 (r = -0.44, p < 0.002), pH (r = -0.68, p < 0.0001), as well as base deficit (r = -0.56, p < 0.0001). A significant correlation was found between EGA and Ua EPO from 27 to 43 weeks of gestation (r = 0.45, p < 0.001, n = 68). One and 5 minute Apgar scores did not correlate with EPO. These findings indicate that EPO correlates strongly with cord gas parameters and thus may serve as a clinically useful marker for both subacute fetal distress and chronic uteroplacental insufficiency.

Apgar Score↗
PubMed1995

Estrogen-induced guinea pig model for uterine leiomyomas: do the ovaries protect?

A guinea pig model was used to study the hormonal control of uterine leiomyomas. Twenty female guinea pigs were divided into four groups--young, old, ovariectomized (OVX), and non-OVX animals--and were given two estradiol-17 beta (E2) silastic implants each for 3-10 mo; another four older OVX animals served as controls and received empty implants. After 3 mo, 100% (8 of 8) of the OVX animals, but none of the OVX controls, developed tumors, mainly on the uterine serosa and the abdominal wall. Electron microscopy and desmin immunostaining demonstrated that the tumors were leiomyomas. In E2-treated animals, E2 levels in serum, leiomyomas, or leiomyoma-free uterine segments rose significantly while serum progesterone (P4) was negligible. Surprisingly, only 8% (1 of 12) of the non-OVX animals developed a tumor. This apparent "ovarian protection" was transient: after 6-9 mo, 50% of the remaining non-OVX animals developed leiomyomas, but these were smaller and fewer than in OVX animals. On the basis of this model, we propose the hypothesis that some factors from the ovaries suppress leiomyoma growth in response to estrogen but that as the ovaries age this protection is diminished, allowing the clinical development of leiomyomas.

Animals↗
PubMed1994

Carbohydrate metabolism studies after one year of using an oral contraceptive containing gestodene and ethinyl estradiol.

UNLABELLED: The objective of the study is to evaluate the effects of a gestodene-containing oral contraceptive on carbohydrate metabolism. The design of the study is prospective. The setting is at University of South Florida Outpatient Unit. The patients consisted of twenty-three normal women desiring contraception. Serum glucose and insulin levels were measured during a three-hour glucose tolerance test at control time and after one year of drug use. RESULTS: All of the one-year glucose values were significantly elevated as well as the fasting and three-hour insulin values. These changes were mostly confined to women over 26 years of age and not in the younger 18 to 23 year olds. An oral contraceptive containing 75 micrograms of gestodene and 30 micrograms of ethinylestradiol can significantly alter carbohydrate metabolism in older women.

Adolescent↗
PubMed1992

Carbohydrate metabolism after three months of using a gestodene-containing monophasic oral contraceptive.

Carbohydrate metabolism was prospectively evaluated in twenty-one normal women prior to and during their use for three months of a monophasic oral contraceptive containing the progestin gestodene plus ethinyl estradiol. The women had a three-hour oral glucose tolerance test using a 75 gram glucose load, measuring serum glucose and insulin levels. The results demonstrate no significant changes in either of the carbohydrate metabolic indices between the two tests. These data support the safety of this new progestin-containing contraceptive.

Adult↗
PubMed1992

Six-month carbohydrate metabolism studies in women using oral contraceptives containing gestodene and ethinyl estradiol.

Twenty-five women had their carbohydrate metabolism prospectively evaluated during the six months that they used a gestodene and ethinyl estradiol monophasic oral contraceptive. Serum glucose and insulin levels were measured during a 75-gram three-hour oral glucose tolerance test. At the six-month test, the three-hour glucose and the fasting and three-hour insulin values were significantly elevated. The literature on carbohydrate metabolism during gestodene oral contraceptive use is also reviewed.

Adult↗
PubMed1991

Carbohydrate metabolic studies in women using a levonorgestrel/ethinyl estradiol containing triphasic oral contraceptive for eighteen months.

Carbohydrate metabolism was evaluated in 17 women before and after 18 months of triphasic oral contraceptive use. The triphasic oral contraceptive contained levonorgestrel and ethinyl estradiol. An oral glucose tolerance test was utilized and both plasma glucose and insulin levels were measured. There were no significant changes in the glucose levels. The fasting insulin level was raised at the 18-month test, whereas the other insulin values were similar. These results demonstrate that the new triphasic oral contraceptive preparations produce minimal carbohydrate metabolic changes.

Adult↗
PubMed1990

Two-year carbohydrate metabolism studies in women using a norethindrone or levonorgestrel triphasic oral contraceptive.

Carbohydrate metabolism was prospectively studied in 28 women using triphasic oral contraceptives (TOC) for two years. They were tested using a 100-gram oral glucose tolerance test with measurements of plasma glucose and insulin levels during the three-hour test. The women were randomly assigned to either a norethindrone-containing TOC or a levonorgestrel-containing TOC. Both types of drugs contained the estrogen ethinyl estradiol. No significant changes were noted in the norethindrone TOC group. The levonorgestrel TOC two-year test had a significant elevation of the 0.5- and 2-hour plasma glucose values and the fasting insulin value. These data show that the two triphasic oral contraceptive preparations affect carbohydrate metabolism differently.

Adult↗