PubMed Health⌕ Search

Biomedical subjects

G E Rice

Publications and source records attributed to G E Rice.

At least 19 recordsLinked to original sources

The role and regulation of the nuclear factor kappa B signalling pathway in human labour.

Within the discipline of reproductive biology, our understanding of one of the most fundamental biological processes is lacking--the cellular and molecular mechanisms that govern birth. This lack of understanding limits our ability to reduce the incidence of labour complications. The incidence of labour complications including: preterm labour; cervical incompetence; and post-date pregnancies has not diminished in decades. The key to improving the management of human labour and delivery is an understanding of how the multiple processes that are requisite for a successful labour and delivery are coordinated to achieve a timely birth. Processes of human labour include the formation of: contraction associated proteins; inflammatory mediators (e.g. cytokines); uterotonic phospholipid metabolites (e.g. prostaglandins); and the induction of extracellular matrix (ECM) remodelling. Increasingly, it is becoming evident that labour onset and birth are the result of cross-talk between multiple components of an integrated network. This hypothesis is supported by recent data implicating various upstream regulatory pathways in the control of key labour-associated processes, including the activity of enzymes involved in the formation of prostaglandins and extracellular matrix remodelling, and mediators of inflammation. Clearly, the biochemical pathways involved in the formation of these mediators represent potential sites for intervention that may translate to therapeutic interventions to delay or prevent preterm labour and delivery. Available data strongly implicate the nuclear factor-kappaB (NF-kappaB) family as candidate upstream regulators of multiple labour-associated processes. Not only do these data warrant further detailed analysis of the involvement of these pathways in the process of human labour but also promise new insights into the key mechanisms that trigger birth and the identification of new therapeutic interventions that will improve the management of labour.

Amnion↗

Translational proteomics: developing a predictive capacity -- a review.

Over the past decade, proteomics has undergone a rapid development and radiation, diversifying across the biochemical landscape. While no single technique yet delivers complete proteomic coverage, application-specific adaptations afford significant opportunity for discovery and the development of predictive capacity (e.g. surrogate biomarker and clinical diagnostics). Targeted proteomic approaches, protein profiling strategies using affinity capture mass spectrometry and solution array represent realistic opportunities to deliver predictive capacity. The aim of this review is to provide an overview of proteomic technologies and how the outcomes delivered by such platforms may be translated into applications of predictive utility in clinical and basic science. In particular, recent applications in protein/peptide profiling (solid-phase affinity capture mass spectrometry and the targeted approach of antibody arrays) and the opportunities they afford researchers within the discipline of reproductive biology to develop new diagnostic and prognostic tests and surrogate biomarkers to improve the delivery of women's health care are considered.

Animals↗

15-Deoxy-Delta(12,14)-prostaglandin J(2) and troglitazone regulation of the release of phospholipid metabolites, inflammatory cytokines and proteases from human gestational tissues.

Phospholipid-derived mediators, inflammatory cytokines and extracellular matrix remodelling enzymes are all involved in the initiation of human labour and delivery. We have previously demonstrated that natural and synthetic PPAR-gamma ligands regulate LPS-stimulated pro-inflammatory cytokine release from human gestational tissues, however, the effect of these ligands on the basal and/or LPS-induced expression of prostaglandins and proteases is not known. Therefore, the aim of this study was to determine the effects of 15d-PGJ(2) and troglitazone on the expression of basal and LPS-stimulated inflammatory mediators in human gestational tissues. Human placenta, amnion and choriodecidua (n=5) were incubated in the presence or absence of 15 microM 15d-PGJ(2) and 30 microM troglitazone under basal and LPS-stimulated (10 microg/ml) conditions. Treatment of placenta, amnion and choriodecidua with both 15d-PGJ(2) and troglitazone decreased basal and LPS-stimulated IL-1beta, IL-6, IL-10 and TNF-alpha release. Basal type II PLA(2) release from placental tissues was also significantly decreased by 15d-PGJ(2) and troglitazone. There was no effects of 15d-PGJ(2) and troglitazone on cPLA(2) protein expression. Both 15d-PGJ(2) and troglitazone significantly decreased basal and LPS-stimulated PGE(2) and PGF(2alpha) release from placenta and amnion. However, in choriodecidua, although 15d-PGJ(2) decreased basal and/or LPS-stimulated PGE(2) and PGF(2alpha) release, there was an increase in PGE(2) and PGF(2alpha) release in the presence of troglitazone. 15d-PGJ(2) and troglitazone inhibited MMP-9 release from human amnion. NF-kappaB DNA binding activity and NF-kappaB p65 protein expression was inhibited by treatment with 15d-PGJ(2) in human amnion. There was no effect of 15d-PGJ(2) or troglitazone on PPAR-gamma protein, and GW9662 failed to alleviate 15d-PGJ(2) and troglitazone inhibition of IL-6 and TNF-alpha release in placenta, amnion and choriodecidua. The data demonstrated in this study suggest that the 15d-PGJ(2) and troglitazone exhibit anti-inflammatory properties in human gestational tissues via PPAR-gamma independent actions.

Anilides↗

Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells.

The incidence of hormone-related diseases such as prostatic, breast, ovarian, and endometrial cancer is lower in Asian populations compared to Western countries. High consumption of soybean products that are rich in phytoestrogens, predominantly genistein, is postulated to be responsible for the lower incidence of hormone-related disease, although the mechanism through which this effect might be mediated is unclear. In this study, microarray analysis was used to identify the changes in gene expression elicited by treatment of the human endometrial cancer cell line, Ishikawa, with genistein at both physiologically achievable and supraphysiological concentrations. Genistein treatment at 5 microM concentration induced multiple changes in gene expression including some implicated in oncogenesis. In contrast, treatment with a supraphysiological concentration of genistein predominantly activated stress response genes and showed very limited overlap with the genes regulated at lower concentrations. Of the genes regulated by genistein, 9.3% were also regulated by 17beta-estradiol suggesting that genistein exerts its response via the estrogen pathway. These results indicate that at physiological concentrations, genistein is able to elicit pleiotropic effects on a variety of pathways believed to be involved in tumorigenesis. Supraphysiological concentrations of genistein, such as those used in many previous studies, elicit changes in gene expression that are unlikely to occur in vivo.

Cell Line, Tumor↗

Lipopolysaccharide and TNF-alpha activate the nuclear factor kappa B pathway in the human placental JEG-3 cells.

Up-regulation of pro-inflammatory cytokines, cyclooxygenase (COX-2) and prostaglandins is a critical factor driving human term labour and inflammation-associated preterm labour. Nuclear factor kappa B (NF-kappaB) is activated in response to a number of inflammatory mediators, including cytokines and lipopolysaccharide (LPS). The aim of this study was (i) to investigate if TNF-alpha and LPS activate the NF-kappaB pathway; and (ii) to use short interfering RNA (siRNA) against inhibitor kappaB kinase (IKK)-beta to confirm the role of the NF-kappaB pathway in the regulation of pro-inflammatory mediators in human placental JEG-3 cells. JEG-3 cells (3 independent experiments) were (i) incubated in the presence or absence of 10 microg/ml LPS or 20 ng/ml TNF-alpha, or (ii) transfected with 100 nM IKK-beta siRNA. Incubation of JEG-3 cells with LPS and TNF-alpha increased the expression of cytoplasmic IKK-beta and phosphorylated IkappaB-alpha, and nuclear NF-kappaB proteins p50 and p65. This was associated with a concurrent increase in COX-2 protein, and IL-6 and PGF2alpha release from JEG-3 cells. Treatment of cells with BAY 11-7082 at 50 microM significantly inhibited basal, LPS- and TNF-alpha-induced NF-kappaB and COX-2 expression, and IL-6 and PGF2alpha release. Transfection of JEG-3 cells with IKK-beta siRNA significantly decreased IL-6 and PGF2alpha release. The data presented in this study demonstrate that pro-inflammatory mediators regulate the NF-kappaB transcription pathway in human JEG-3 cells, and the IKK-beta/NF-kappaB pathway is a regulator of inflammatory mediators in placental JEG-3 cells.

Cell Line, Tumor↗

Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma.

The peroxisome proliferator-activated receptors (PPARs) belong to a subclass of nuclear hormone receptor that executes important cellular transcriptional functions. Previous studies have demonstrated the expression of PPARgamma in several tumours including colon, breast, bladder, prostate, lung and stomach. This study demonstrates the relative expression of PPARgamma in normal ovaries and different pathological grades of ovarian tumours of serous, mucinous, endometrioid, clear cell and mixed subtypes. A total of 56 ovarian specimens including 10 normal, eight benign, 10 borderline, seven grade 1, nine grade 2 and 12 grade 3 were analysed using immunohistochemistry. Immunoreactive PPARgamma was not expressed in normal ovaries. Out of eight benign and 10 borderline tumours, only one tumour in each group showed weak cytoplasmic PPARgamma expression. In contrast, 26 out of 28 carcinomas studied were positive for PPARgamma expression with staining confined to cytoplasmic and nuclear regions. An altered staining pattern of PPARgamma was observed in high-grade ovarian tumours with PPARgamma being mostly localized in the nuclei with little cytoplasmic immunoreactivity. On the other hand, predominant cytoplasmic staining was observed in lower-grade tumours. Significantly increased PPARgamma immunoreactivity was observed in malignant ovarian tumours (grade 1, 2 and 3) compared to benign and borderline tumours (chi2 = 48.80, P < 0.001). Western blot analyses showed significant elevation in the expression of immunoreactive PPARgamma in grade 3 ovarian tumours compared with that of normal ovaries and benign ovarian tumours (P < 0.01). These findings suggest an involvement of PPARgamma in the onset and development of ovarian carcinoma and provide an insight into the regulation of this molecule in the progression of the disease.

Adenocarcinoma, Clear Cell↗

Proteomic-based identification of haptoglobin-1 precursor as a novel circulating biomarker of ovarian cancer.

Screening for specific biomarkers of early-stage detection of ovarian cancer is a major health priority due to the asymptomatic nature and poor survival characteristic of the disease. We utilised two-dimensional gel electrophoresis (2DE) to identify differentially expressed proteins in the serum of ovarian cancer patients that may be useful as biomarkers of this disease. In this study, 38 ovarian cancer patients at different pathological grades (grade 1 (n=6), grade 2 (n=8) and grade 3 (n=24)) were compared to a control group of eight healthy women. Serum samples were treated with a mixture of Affigel-Blue and protein A (5 : 1) for 1 h to remove high abundance protein (e.g. immunoglobulin and albumin) and were displayed using 11 cm, pH 4-7 isoelectric focusing strips for the first dimension and 10% acrylamide gel electrophoresis for the second dimension. Protein spots were visualised by SYPRO-Ruby staining, imaged by FX-imager and compared and analysed by PDQuest software. A total of 24 serum proteins were differentially expressed in grade 1 (P<0.05), 31 in grade 2 (P<0.05) and 25 in grade 3 (P<0.05) ovarian cancer patients. Six of the protein spots that were significantly upregulated in all groups of ovarian cancer patients were identified by nano-electrospray quadrupole quadrupole time-of-flight mass spectrometry (n-ESIQ(q)TOFMS) and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOFMS) as isoforms of haptoglobin-1 precursor (HAP1), a liver glycoprotein present in human serum. Further identification of the spots at different pathological grades was confirmed by Western blotting using monoclonal antibody against a haptoglobin epitope contained within HAP1. Immunohistochemical localisation of HAP1-like activity was present in malignant ovarian epithelium and stroma but strong immunostaining was present in blood vessels, areas with myxomatous stroma and vascular spaces. No tissue localisation of HAP1-like immunoreactivity was observed in normal ovarian surface epithelium. These data highlight the need to assess circulating concentration of HAP1 in the serum of ovarian cancer patients and evaluate its potential as a biomarker in the early diagnosis of ovarian cancer.

Biomarkers, Tumor↗

Phospholipase A2 isozymes in pregnancy and parturition.

Mammalian cells contain several structurally different phospholipase (PLA2) enzymes that exhibit distinct localisation, function and mechanisms of regulation. PLA2 isozymes have been postulated to play significant roles in the parturition process. Both secretory and cytosolic PLA2 isozymes have been identified in human gestational tissues, and there is differential expression of these PLA2 isozymes in human fetal membranes and placenta obtained at preterm and term. The aims of this commentary are: (1) to review recent data concerning the expression, role and regulation of PLA2 isozymes in human gestational tissues; and (2) to present novel data demonstrating the regulation of PLA2 isozymes in human gestational tissues by nuclear factor-kappa B (NF-kappaB) and peroxisome proliferator-activated receptor (PPAR)-g.

Female↗

Correlation of tumor- and stromal-derived MT1-MMP expression with progression of human ovarian tumors in SCID mice.

OBJECTIVE: Human ovarian carcinoma samples were orthotopically implanted into SCID mice to investigate the contribution of matrix metalloproteases (MMPs) to the spread of ovarian tumors. METHODS: Mice were inoculated with patient tumor samples, and developed ovarian tumors over a 16-week period with metastasis occurring in some mice. Species-specific quantitative RT-PCR was used to identify the source of tumor-associated MMPs. RESULTS: Membrane-type (MT)1-MMP mRNA was significantly increased in high-grade tumors, tumors with evidence of serosal involvement, and tumors in which distant metastases were detected. The increase in MT1-MMP expression was predominantly from the human tumor cells, with a minor contribution from the mouse ovarian stroma. Neither human nor mouse MT2-MMP were correlated with tumor progression and MT3-MMP levels were negligible. While tumor cells did not produce significant amounts of MMP-2 or MMP-9, the presence of tumor was associated with increased levels of MMP-2 expression by mouse ovarian stroma. Stromal-derived MT1-MMP was greater in large tumors and was associated with stromal MMP-2 expression but neither was significantly linked with metastasis. CONCLUSIONS: These studies indicate that tumor-derived MT1-MMP, more so than other gelatinolytic MMPs, is strongly linked to aggressive tumor behavior. This orthotopic model of human ovarian carcinoma is appropriate for studying ovarian tumor progression, and will be valuable in the further investigation of the metastatic process.

Animals↗

Altered placental oxidative stress status in gestational diabetes mellitus.

Oxidative stress has been clearly linked to type 2 diabetes mellitus, however, limited data are available on the involvement of oxidative stress in gestational diabetes mellitus (GDM), a disease of similar pathophysiology. The aim of this study was to investigate the status of placental oxidative stress in healthy pregnant women and women with GDM. The hypothesis to be tested was that tissue markers of oxidative stress are significantly increased in GDM compared to normal placental tissues. Markers of oxidative stress measured were the release of 8-isoprostane (8-epi-prostaglandin F(2alpha)) from human term placental explants (n=11), the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase (n=10), and protein carbonyl content (n=12). Placental release of 8-isoprostane was 2-fold greater from women with GDM (P<0.001) compared to healthy pregnant women. Superoxide dismutase activity and protein carbonyl content were elevated in placentae obtained from women with GDM (P<0.04 and P<0.004 respectively), whilst there was no significant difference in the activity of glutathione peroxidase. These data demonstrate the presence of oxidative stress in the placenta from women with GDM, in addition to the induction of a key antioxidant, collectively indicating a state of existing oxidative stress in this condition.

Biomarkers↗

Overexpression of alpha(v)beta6 integrin in serous epithelial ovarian cancer regulates extracellular matrix degradation via the plasminogen activation cascade.

Recent evidence suggests that integrins are involved in the multi-step process of tumour metastasis. The biological relevance of alpha(v) integrins and associated beta-subunits in ovarian cancer metastasis was examined by analysing the expression of these cell surface receptors in nine ovarian cancer cell lines and also in the primary human ovarian surface epithelial cell line (HOSE). beta1, beta3 and beta5 subunits were present in all ten ovarian cell lines. beta6 subunit was present at varying levels in eight out of nine cancer cell lines but was absent in the HOSE cell line. Immunohistochemical staining showed that beta6 was present in both non-invasive (borderline) and high-grade ovarian cancer tissues but was absent in benign and normal ovarian tissue. High alpha(v)beta6 integrin expressing ovarian cancer cell lines had high cell surface expression of uPA and uPAR. Ovarian cancer cell lines expressing high to moderate level of alpha(v)beta6 integrin demonstrated ligand-independent enhanced levels of high molecular weight (HMW)-uPA and pro-matrix metalloproteinase 2 and 9 (pro-MMP-2 and pro-MMP-9) expression in the tumour-conditioned medium. High and moderate expression of alpha(v)beta6 integrin correlated with increased plasminogen-dependent degradation of extracellular matrix which could be inhibited by inhibitors of plasmin, uPA and MMPs or by monoclonal antibody against uPA, MMP-9 or alpha(v)beta6 integrin. These results suggest that endogenous de novo expression of alpha(v)beta6 integrin in ovarian cancer cells may contribute to their invasive potential, and that alpha(v)beta6 expression may play a role in ovarian cancer progression and metastasis.

Antigens, Neoplasm↗

Proteomic analysis of human plasma: failure of centrifugal ultrafiltration to remove albumin and other high molecular weight proteins.

Determination of specific low abundance proteins, usually by radiolabelled or enzyme-linked immunoassays in serum or plasma is widely used in diagnostic medicine. Substitution of these assays by a proteomic approach has been suggested, but this methodology has far from realised its potential as a diagnostic tool. The main protein fractions of plasma represent more than 80% of total protein, making the hundreds or even thousands of other proteins difficult to detect by two-dimensional electrophoresis (2-DE). Thus, loading sufficient sample to detect trace proteins invariably means excessive loading of albumin and other high abundance proteins. The aim of this study was to determine whether centrifugal ultrafiltration of whole plasma could be used to eliminate proteins exceeding a desired molecular weight cut-off. Cellulose filters with a 30 kDa molecular weight cut-off were used with whole plasma, and total protein was determined before and after ultrafiltration. Samples were processed by routine methods for 2-DE using 18 cm, pH 3-10 isoelectric focusing strips for the first dimension and 7-15% gradient gels for the second dimension followed by silver staining. Gel analysis of the retentate fraction (> 30 kDa) revealed a typical 2-DE plasma profile with most of the major landmark proteins in place and as expected, the gels lacked many of the smaller (< 30 kDa) proteins. Comparison with gels of the filtrate fraction (> 30 kDa) revealed very little difference. Not only were many of the higher molecular weight proteins still present, but some of the smaller < 30 kDa landmark proteins were absent. Overall, gels of both the retentate and filtrate fractions were less informative than gels of whole plasma.

Blood↗

Glucose-induced release of tumour necrosis factor-alpha from human placental and adipose tissues in gestational diabetes mellitus.

AIMS: The cytokine tumour necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of insulin resistance in Type 2 diabetes mellitus, but limited data are available in relation to gestational diabetes mellitus (GDM), a disease in which similar biochemical abnormalities exist. We investigated the effect of exogenous glucose on the release of TNF-alpha from placental and adipose (omental and subcutaneous) tissue obtained from normal pregnant women, and women with GDM. METHODS: Human tissue explants were incubated for up to 24 h and TNF-alpha concentration in the incubation medium quantified by ELISA. The effect of normal (5 mmol/l) and high (15 and 25 mmol/l) glucose concentrations on the release of TNF-alpha was assessed. RESULTS: In placental and subcutaneous adipose tissues obtained from women with GDM (n = 6), TNF-alpha release was significantly greater under conditions of high glucose compared with normal glucose (placenta, 25 mmol/l 5915.7 +/- 2579.6 and 15 mmol/l 4547.1 +/- 2039.1 vs. 5 mmol/l 1897.1 +/- 545.5; subcutaneous adipose tissue, 25 mmol/l 423.5 +/- 207.0 and 15 mmol/l 278.5 +/- 138.7 vs. 5 mmol/l 65.3 +/- 28.5 pg/mg protein; P < 0.05). In contrast, there was no stimulatory effect of high glucose on TNF-alpha release by tissues obtained from normal pregnant women (n = 6) (placenta, 25 mmol/l 1542.1 +/- 486.2 and 15 mmol/l 4263.3 +/- 2737.7 vs. 5 mmol/l 5422.4 +/- 1599.0; subcutaneous adipose tissue, 25 mmol/l 189.8 +/- 120.4 and 15 mmol/l 124.5 +/- 32.3 vs. 5 mmol/l 217.9 +/- 103.5 pg/mg protein). CONCLUSIONS: These observations suggest that tissues from patients with GDM release greater amounts of TNF-alpha in response to high glucose. As TNF-alpha has been previously implicated in the regulation of glucose and lipid metabolism, and of insulin resistance, these data are consistent with the hypothesis that TNF-alpha may be involved in the pathogenesis and/or progression of GDM.

Adipose Tissue↗

Type II phospholipase A2 in preterm human gestational tissues.

Maternal genital tract infections and the associated inflammatory response may contribute to the onset of many cases of preterm labour. Type II phospholipase A(2)(PLA2) hydrolyses glycerophospholipids, releasing free fatty acid for conversion into potent biological mediators, such as prostaglandins, which play a significant role in both the onset and progression of human labour and the activation of inflammatory reactions. The aim of this study was to quantify immunoreactive (ir) Type II PLA2 in placenta, amnion and choriodecidua collected from women delivering prematurely or due to histological chorioamnionitis, and to compare levels to those at term. Tissues were assayed for ir Type II PLA2 by ELISA and expressed as ng/mg tissue protein. Ir Type II PLA2 tissue content was significantly higher in preterm (n=26) amnion and choriodecidua, but not in the placenta when compared to tissues obtained at term (n=42). When the data were stratified with respect to labour status, ir Type II PLA2 content was significantly higher in the preterm not-in-labour group (NIL, n=17) than the preterm in labour group (IL, n=9) in the amnion. When the NIL group was analysed with respect to membrane rupture, women who had spontaneously ruptured membranes (n=6) expressed significantly greater ir Type II PLA2 than those that had intact membranes (n=11) in both the amnion and choriodecidua but not in the placenta. No significant difference was observed between the preterm IL group (n=9) and the group with histological chorioamnionitis (n=14). The data obtained in this study support a role for Type II PLA2 in association with spontaneous rupture of membranes.

Adult↗

Antisense oligonucleotide inhibition of type II phospholipase A2 expression, release and activity in vitro.

Phospholipase A2 (PLA2) enzymes that regulate the release of arachidonic acid from cell membrane phospholipids represent a crucial rate-limiting step for the prostaglandin biosynthetic pathway. The aim of this study was to determine the mechanism of action and effects of type II PLA2 antisense oligonucleotides on type II PLA2 mRNA relative abundance, and the release of PLA2 enzymatic activity and prostaglandin F2alpha (PGF2alpha) in vitro. A human placental explant system was used to evaluate the effects of the type II PLA2 specific antisense oligonucleotides A (5'-GGGTGGGTATAGAAGGGCTCC-3', complementary to the base sequence 697-717 of the type II PLA2 gene) and B (5'-TTTTTGATTTGCTAATTGCTT-3', complementary to the base sequence 821-841 of the type II PLA2 gene). PLA2 activity released from explants was quantified by radiolabelled substrate assay using 14C-phosphatidylethanolamine (PE), and PGF2alpha content was analyzed by radioimmunoassay. Compared with control, the release of PLA2 activity and PGF2alpha was significantly reduced over the 24-h period by treatment with both antisense oligonucleotides (P< 0.05). At this concentration, type II PLA2 mRNA abundance was also significantly reduced by both antisense oligonucleotides A and B (P< 0.05). This data demonstrates the efficacy of antisense oligonucleotide inhibition of secretory PLA2 (sPLA2) expression and activity, and the contribution of sPLA2 to placental prostaglandin production.

Blotting, Northern↗

Interleukin-6 and interleukin-8 in newborn bacterial infection.

The objective of this study is to determine the plasma concentrations and diagnostic accuracy of interleukin-6 (IL-6) and interleukin-8 (IL-8) in newborn infection. One hundred and one newborn infants with clinical signs of infection during their primary hospitalization were investigated with the minimum of a blood culture, C-reactive protein (CRP), full blood examination (FBE), and cytokine concentrations (IL-6 and IL-8). Infection in infants was classified without knowledge of cytokine levels into four groups-definite (n = 11), probable (n = 12), uncertain (n = 52), and nil (n = 26). The median concentrations of IL-6 and IL-8 were significantly higher in the definitely infected group compared with the other three groups (p <0.05). At the cut-off concentration of highest accuracy, IL-6 (>175 pg/mL) and IL-8 (>28 pg/mL) had similar sensitivities (80 and 82%, respectively) and specificities (91 and 81%, respectively). Cut-off concentrations could be identified with improved sensitivities (90% for IL-6 and 100% for IL-8) that maintained specificity >50%. However, the confidence intervals were wide for all sensitivities and specificities. IL-6 and IL-8 had little diagnostic accuracy in infants with probable infection. IL-6 and IL-8 concentrations increase early in newborn infants with definite infection.

C-Reactive Protein↗

The effect of vascular coiling on venous perfusion during experimental umbilical cord encirclement.

OBJECTIVE: The aim of these studies was to compare venous perfusion in umbilical cords subjected to a standardized tight encirclement force. Comparisons were made between cords from normal pregnancies and those complicated by gestational diabetes mellitus and intrauterine growth restriction. STUDY DESIGN: The cannulated cord segment was wrapped around a plastic container, which in turn was attached with nylon string to a hanging graduated measuring cylinder in which known volumes of water could be applied for weight. The cord was perfused with Krebs solution to a constant venous perfusion pressure of 40 mm Hg. Weights of 100-g increments were applied until total cessation of venous perfusion was observed. The weight, length, number of vascular coils, and degree of hydration were recorded for each cord. The coiling index was defined as the number of vascular coils per 10 cm of cord. RESULTS: Regression analysis of 34 cords (normal, n = 16; gestational diabetes mellitus, n = 12; intrauterine growth restriction, n = 6) identified a significant inverse correlation (P =.0003, Spearman rank correlation) between coiling index and the minimum weight required to occlude venous perfusion. Cords from pregnancies complicated by intrauterine growth restriction displayed a higher frequency of vascular coiling and were more easily occluded (median weight, 350 g) than were cords from pregnancies complicated by gestational diabetes mellitus, which were less coiled and tended to resist occlusion (median weight, 1100 g). CONCLUSION: During experimental cord encirclement there was a significant inverse relationship between vascular coiling and susceptibility to cord venous occlusion when traction was applied to the encirclement.

Biomechanical Phenomena↗