Search PubMed⌕ Search

Biomedical subjects

Phillip R Bennett

Publications and source records attributed to Phillip R Bennett.

10 recordsLinked to original sources
PubMed2003

The effects of non-steroidal anti-inflammatory compounds on human myometrial contractility.

OBJECTIVE: To investigate the effects of inhibitors of COX-1 or COX-2 on myometrial prostaglandin synthesis and on spontaneous contractions in human myometrium. METHODS: Cultured myometrial cells were incubated with SC 58560 (COX-1 selective inhibitor) or SC 58236 (COX-2 selective inhibitor), and the production of prostaglandins determined by ELISA. Spontaneously contracting strips of isolated gravid human lower segment myometrium were incubated with SC 58236, meloxicam, DFU, or nimesulide (COX-2 selective inhibitors), with SC 58560 (COX-1 selective inhibitor) or indomethacin (non-selective inhibitor). RESULTS: SC 58236 inhibited the production of prostaglandins from myometrial cells, whereas SC 58560 had less effect. Nimesulide (100 microM) and indomethacin (300 microM) completely inhibited myometrial contractions, whereas meloxicam, DFU, SC 58236 and SC 58560 had less effect. CONCLUSIONS: There was no relationship between the inhibition of prostaglandin production and the effects of the compounds on contractility. Myometrial prostaglandin synthesis does not seem to be essential for spontaneous contractility.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Progesterone represses interleukin-8 and cyclo-oxygenase-2 in human lower segment fibroblast cells and amnion epithelial cells.

Labor is preceded by cervical ripening through upregulation of interleukin (IL)-1beta, IL-8, and increased prostaglandin synthesis via inducible type 2 cyclooxygenase (COX-2). Progesterone maintains myometrial quiescence during pregnancy. In this study, we examined the effects of IL-1beta and progesterone on IL-8 and prostaglandin E2 (PGE2) synthesis and IL-8 and COX-2 mRNA and promoter activity in amnion cells and lower segment fibroblast (LSF) cells. In both cell types, progesterone had no effect on basal IL-8 or PGE2 synthesis. In LSF cells, IL-1beta significantly increased IL-8 and PGE2 synthesis and COX-2 and IL-8 mRNA expression, but progesterone significantly attenuated these effects. In prelabor amnion cells, IL-1beta also increased IL-8 and PGE2 synthesis and both COX-2 and IL-8 mRNA and promoter expression; however, progesterone significantly attenuated these effects on IL-8 and PGE2 synthesis and COX-2 expression. In postlabor amnion cells, IL-1beta increased IL-8 and PGE2 synthesis and COX-2 expression, but progesterone did not attenuate the effect of IL-1beta upon IL-8 synthesis. Progesterone repression of IL-8 and COX-2 in LSF cells suggests that IL-8 and COX-2 have similar regulatory mechanisms in LSF cells and that progesterone may play a role in maintenance of cervical competence. The lack of effect of progesterone on IL-8 in postlabor cells may be the result of downregulation of the progesterone receptor during labor.

Amnion↗
PubMed2003

CD34+ cells from first-trimester fetal blood are enriched in primitive hemopoietic progenitors.

OBJECTIVE: The purpose of this study was to investigate whether purified CD34(+) cells from first-trimester fetal blood are a source of primitive and committed hemopoietic progenitors. STUDY DESIGN: CD34(+) cells from first-trimester fetal blood and term cord blood were assayed for committed hemopoietic progenitor cells, high proliferative potential colony-forming cells, and long-term culture-initiating cells. RESULTS: First-trimester CD34(+) cells that were compared with cells at term generated fewer hemopoietic progenitor cells and fewer high proliferative potential colony-forming cells with lower recloning efficiency(P <.001). First-trimester CD34(+) cells tended to contain more long-term culture-initiating cells, both in bulk cultures and by limiting dilution analysis. The ratio between committed and primitive progenitors was 3 in the first-trimester and 20 in the term cord blood, respectively. CONCLUSION: First-trimester fetal blood is enriched in primitive (compared with committed) hemopoietic progenitors and may be an advantageous source of stem cells for prenatal therapy.

Antigens, CD34↗
PubMed2003

A double-blind randomized study of fetal side effects during and after the short-term maternal administration of indomethacin, sulindac, and nimesulide for the treatment of preterm labor.

OBJECTIVE: The purpose of this study was to establish whether nimesulide causes fewer fetal side effects than indomethacin or sulindac after short-term maternal exposure for tocolysis. STUDY DESIGN: This was a double-blind, double-dummy prospective randomized study with three drug treatment groups (n = 10 per group) that were comprised of subjects who were at 28 to 32 weeks of gestation with preterm contractions. The subjects were treated in the delivery suites of two busy inner-city teaching hospitals; the intervention consisted of 48 hours of treatment and with 72 hours of follow-up observation with indomethacin 100 mg (twice daily), sulindac 200 mg (twice daily), or nimesulide 200 mg (twice daily). The amniotic fluid index, hourly fetal urine production, and ductal Doppler pulsatility index observations were monitored before the treatment and at 4, 24, 48, 72, and 120 hours after the treatment was started. The statistical analysis used repeated measures analysis of variance, Bonferroni test, and Bland-Altman agreement. Significance assumed when the probability value was <.05. RESULTS: Each drug caused a significant reduction in all three observations over the 48-hour treatment period, which recovered to pretreatment levels by 72 hours after treatment. There were no significant differences among drugs for any of these effects. CONCLUSION: Nimesulide causes similar short-term fetal side effects to indomethacin and sulindac.

Adult↗
PubMed2003

Characterization of first trimester fetal erythroblasts for non-invasive prenatal diagnosis.

Isolating fetal erythroblasts from first trimester maternal blood offers a promising non-invasive alternative for prenatal diagnosis. The aim of this study was to characterize the biological properties of first trimester primitive erythroblasts to facilitate their enrichment from first trimester maternal blood. Primitive erythroblasts were the predominant cell type until 12 weeks gestation, after which time their numbers declined steeply; 100% were epsilon-globin-positive versus <0.06% definitive erythroblasts. Buoyant densities of first trimester fetal erythroblasts ranged from 1.077 to 1.130 g/ml, and optimal recoveries were obtained with Percoll 1118. Although primitive erythroblasts carried a negative surface charge and were resistant to NH(4)Cl lysis, these properties had only a limited role in fetal cell enrichment. Immunophenotyping showed that primitive, like definitive, erythroblasts were GPA+, CD47+, CD45- and CD35-, whereas CD71 expression was weak/undetectable on primitive erythroblasts but strongly positive on 100% of definitive erythroblasts; primitive erythroblasts were also CD36- whereas definitive erythroblasts were CD36+. We therefore used CD45/GPA selection of Percoll 1118-separated cells to demonstrate successful enrichment of male epsilon-globin-positive fetal erythroblasts from model mixtures, and as proof of principle from some first trimester maternal blood samples. Fetal cell enrichment protocols based on first trimester epsilon-globin-positive primitive erythroblasts may allow reliable enrichment of fetal cells from maternal blood for early non-invasive prenatal diagnosis of genetic disorders.

Ammonium Chloride↗
PubMed2002

Expandability of haemopoietic progenitors in first trimester fetal and maternal blood: implications for non-invasive prenatal diagnosis.

OBJECTIVES: Selective amplification of rare fetal cells in maternal blood is a potential strategy for non-invasive prenatal diagnosis. We assessed the proliferative potential of first trimester fetal progenitors compared to maternal ones. METHODS: Fetal and maternal haemopoietic progenitors were cultured separately and in two model mixtures: (i) co-cultures of male fetal nucleated cells mixed with maternal nucleated cells and (ii) co-cultures of malefetal CD34+ cells with maternal CD34+ cells. Cell origin was detected by X-Y fluorescence in situ hybridisation (FISH) RESULTS: The frequency of haemopoietic progenitors in first trimester fetal blood (predominantly CFU-GEMM) differed from those in peripheral blood from pregnant women (predominantly BFU-e). First trimester haemopoietic progenitors formed larger colonies (p=0.0001) and their haemoglobinisation was accelerated compared to those of maternal origin (p<0.001). CD34+ fetal haemopoietic progenitor cells could be expanded four times more than their maternal counterparts (median 235.8-fold, range 174.0-968.0 vs 71.9-fold, range 41.1-192.0; p=0.003). While selective expansion of fetal cells was not observed in the mononuclear cell model, the CD34+ cell rare event mixtures produced a 463.2-fold (range 128.0-2915.0) expansion of fetal cells. CONCLUSION: Selective expansion of first trimester fetal haemopoietic progenitors may be useful for amplifying fetal cells from maternal blood.

Antigens, CD34↗
PubMed2002

Ultrasound-indicated cervical cerclage: outcome depends on preoperative cervical length and presence of visible membranes at time of cerclage.

OBJECTIVE: The purpose of this study was to assess cases of ultrasound-indicated cervical cerclage and to relate preoperative cervical length, operative findings, postoperative cervical length, and pregnancy outcome to establish the appropriate criteria to offer cervical cerclage. STUDY DESIGN: A prospective observational study comprised 380 women at high risk of preterm labor who underwent serial transvaginal ultrasonographic assessment of cervical length. Seventy-three women had criteria for and underwent cervical cerclage. Data concerning preoperative cervical length, operative findings, postoperative cervical length, and pregnancy outcome were collected. Statistical analysis was performed with Mann-Whitney and Fisher exact tests. RESULTS: There was a significant increase in median cervical length after cerclage, 15.0 versus 25.0 mm (P <.0001). Preoperative cervical length and postoperative upper cervical length were independently better predictors of outcome than postoperative entire cervical length. Fetal membranes were visible in 18% of cases at the time of suture insertion, which was associated with a significantly worse outcome, regardless of preoperative cervical length. Of those 41 women with a very short preoperative cervical length (< or = 15 mm), outcome was significantly worse in those women with visible fetal membranes at the time of cerclage compared with those women with no visible fetal membranes at the time of cerclage: median gestational age at delivery, 23 weeks versus 37 weeks 4 days (P =.002); suture insertion to delivery interval, 19 days versus 108 days (P =.0004); and fetal survival rates, 50% versus 86% (P =.03). CONCLUSION: In a high-risk population that undergoes serial transvaginal ultrasound surveillance of cervical length, the presence of visible fetal membranes at the time of suture insertion, regardless of preoperative cervical length, is associated with a poor outcome. Fetal membranes were not visible in any cases with a preoperative cervical length of >15 mm. These findings lend support to a practice of offering cerclage at or above a cervical length of 15 mm.

Adult↗
PubMed2002

Preterm labour.

Studies in the past year have clarified the roles of inflammatory mediators in preterm labour. Exploration of possible genetic predisposition is just beginning. Ultrasound measurement of cervical length has the potential to predict women at risk of preterm delivery several weeks before it occurs. Biochemical testing such as fetal fibronectin can possibly increase its predictive value and differentiate true preterm labour from more innocent preterm contractions. The use of antibiotics for preterm premature rupture of membranes has been clarified with the ORACLE I trial, which shows health benefits for the neonate with the use of erythromycin, whereas antibiotics do not seem to play a beneficial role in spontaneous preterm labour without evidence of clinical infection. There have been further studies suggesting that agents other than beta-agonists are preferable for acute tocolysis and that repeated doses of corticosteroids should be used with caution.

Adrenal Cortex Hormones↗