External validity of first-trimester algorithms in the prediction of pre-eclampsia disease severity.

OBJECTIVE: To compare disease features in women with pre-eclampsia between those who are correctly identified (true positive) and those who are missed (false negative) when applying first-trimester prediction algorithms for pre-eclampsia to a prospectively enrolled population. METHOD: Six first-trimester early (requiring delivery < 34 weeks' gestation) pre-eclampsia algorithms were applied to a prospective cohort of singleton pregnancies enrolled at first-trimester screening. Maternal outcomes, neonatal outcomes and severity parameters for pre-eclampsia were compared between true-positive and false-negative predictions. RESULTS: Twenty of 2446 (0.8%) women developed early pre-eclampsia, with 65% of these developing severe features and 20% HELLP syndrome. At enrollment, true-positive cases were more likely to be African-American and chronically hypertensive, while false-negative cases were more likely to be Caucasian. At delivery, true-positive cases were more likely to have pre-eclampsia superimposed on hypertension, severely elevated blood pressure and creatinine level > 1.1 mg/dL. False-negative cases were more likely to have HELLP syndrome (all P < 0.05). CONCLUSION: In an urban population with a high prevalence of chronic hypertension, patients who are correctly identified by first-trimester screening models are more likely to develop pre-eclampsia superimposed on chronic hypertension with severely elevated blood pressure and evidence of renal failure. In contrast, patients who are missed by these algorithms are more likely to have HELLP syndrome. Further research is needed to confirm these findings and the algorithm adjustments that may be necessary to better predict pre-eclampsia phenotypes.

Enhanced transduction of mouse bone marrow-derived dendritic cells by repetitive infection with self-complementary adeno-associated virus 6 combined with immunostimulatory ligands.

The potential of adeno-associated virus (AAV)-based vectors in human gene therapy is being explored for several diseases. Although sustained transgene expression and low vector-associated cellular immunity are attractive features of recombinant (r) AAV, the wider application of rAAV vectors encapsidated in serotype 2 capsid is hampered by poor transduction efficiency in many target tissues. These include ex vivo-generated dendritic cells (DC), which have demonstrated promising immunotherapeutic activity. We report here that efficient transduction of mouse bone marrow-derived DC can be achieved with self-complementary (sc) rAAV encapsidated in serotype 6 capsid. Sequential exposure of DC precursor cultures to IL-4 and GM-CSF with sc rAAV6 encoding the human tumor antigen, carcinoembryonic antigen (CEA), for 7 days followed by activation with CpG oligodeoxynucleotides (ODN) and anti-mouse CD40 antibody resulted in highly efficient transduction of DC. DC surface markers as determined by flow cytometry analysis of sc rAAV6-transduced DC were comparable to nontransduced DC. Efficiency of vector transduction and transgene expression were confirmed by immunostaining and real-time PCR. Microarray analysis of RNA from CpG ODN and CD40 antibody stimulated sc AAV6-transduced DC revealed upregulation of transcription factors and cytokines involved in immune activation and downregulation of inhibitory factors, suggesting a possible role of transcriptional activation in the observed effect. The adoptive transfer into syngeneic mice of the ex vivo-transduced and activated DC resulted in the development of CEA-specific antibody and T-helper 1-associated immune responses. Immunized mice also developed antibody to AAV6 capsid protein, which did not crossreact with AAV2 capsid protein. These studies demonstrate the potential utility of sc rAAV serotype 6-based vectors in transduction of DC for genetic vaccination approaches.

Elevated amniotic fluid interleukin-6 levels during the early second trimester are associated with greater risk of subsequent preterm delivery.

PROBLEM: Subclinical intra-amniotic infection is often associated with preterm delivery and may precede it by several weeks. We tested the hypothesis that Interleukin-6 (IL-6) may be elevated in the midtrimester amniotic fluid of pregnancies destined to deliver preterm. METHODS: A historical cohort study was designed to compare the amniotic fluid (AF) concentrations of IL-6 at 14-20 weeks in a group of women subsequently delivering at < or = 34 weeks (n = 13) with those of women delivering at term (n = 166). Included were singleton gestations with no evidence of fetal structural or chromosomal abnormalities, or maternal conditions known to be associated with preterm delivery (n = 179). Levels of IL-6 were measured by immunoassay and correlated with demographic and pregnancy outcome information. Statistical analysis included correlation, one-way ANOVA after log-transformation, contingency tables, logistic regression, and receiver operator characteristic (ROC) curve analysis. RESULTS: There was an inverse correlation between AF IL-6 levels at 15-20 weeks and gestational age at delivery (r = -0.16, P = 0.03). Women delivering at < or = 34 weeks had significantly higher median AF IL-6 levels (570 pg/ml versus 330 pg/ml, P < 0.0001), rate of African American race (50% versus 12%, P = 0.004), and of infants with birth weights < 10th centile (31% versus 7%, P = 0.02) than women delivering at > or = 37 weeks. Logistic regression analysis showed that IL-6 was independently associated with PTD at < or = 34 weeks after controlling for race and birth weight centiles (P = 0.039). CONCLUSIONS: AF IL-6 at 15-20 weeks can identify patients at risk for PTD at < or = 34 weeks, suggesting that a portion of PTD cases have inciting events that take place during the early second trimester.

Evaluation of early second trimester maternal serum creatine kinase isoenzyme BB as a marker of poor pregnancy outcome.

We hypothesized that maternal serum levels of the isoenzyme creatine kinase (CK)-BB, which is highly expressed in the placenta, may be elevated during the early second trimester in gestations destined to deliver prematurely or of a small-for-gestational-age infant (birthweight below 10th percentile). To test this hypothesis, we compared maternal serum CK-BB levels and percentage of CK-BB over total CK, in 69 normal pregnancies (delivering at term of appropriate-for-gestational-age infants) with those of 25 cases complicated by preterm delivery at < or = 34 weeks (n = 14), of a small-for-gestational-age infant (n = 8), or both (n = 3). No differences were present in maternal serum CK BB levels between normal and complicated pregnancies. Moreover, no correlation was found between gestational age at delivery and CK BB levels (r = 0.03; p = 0.7).

Second-trimester amniotic fluid or maternal serum interleukin-10 levels and small for gestational age neonates.

OBJECTIVE: To evaluate if interleukin-10 levels in either early second-trimester amniotic fluid (AF) or maternal serum can be utilized as a predictor of the subsequent occurrence of small for gestational age (SGA) infants after controlling for gestational age at delivery. METHODS: We identified patients who underwent genetic amniocentesis for standard genetic indications or maternal blood sampling for maternal serum alpha-fetoprotein (MSAFP)/triple screen between January 1992 and February 1995 with available follow-up delivery data. Small for gestational age was defined as birth weight less than the tenth percentile for gestational age. Control patients were matched for gestational age at delivery, maternal age, race, and parity with at least two controls for each study patient. We excluded patients with maternal immune disease, chronic hypertension, diabetes, asthma, congenital heart disease, multiple gestation, and fetuses with structural or chromosomal anomalies. Second-trimester AF and serum samples were assayed for interleukin-10. Potential confounding variables considered were MSAFP level, smoking history, pregnancy-induced hypertension, and neonatal gender. The interleukin-10 levels were normalized using natural log transformation for statistical analysis. Statistical analysis included chi 2, Fisher exact test, and analysis of variance, with P < .05 considered significant. RESULTS. From the AF data base, 18 patients (6%) delivered SGA neonates and were matched with 46 controls. From the maternal serum data base, 13 patients (7%) delivered SGA neonates and were matched with 45 controls. Neither AF nor maternal serum interleukin-10 levels were significantly different in patients subsequently delivering SGA neonates compared with controls (AF: median 21.0 pg/mL. [range 13.8-27.6] versus 17.5 pg/mL. [range 8.9-362.12], P = .18; serum: median 15.7 pg/mL [range 9.9-73.5] versus 18.7 pg/mL [range 9.7-71.7], P = .60, respectively). No significant differences were identified in gestational age at sampling, maternal smoking history, pregnancy-induced hypertension, or elevated MSAFP in patients delivering SGA neonates compared with controls (P > .05 for each). As expected, birth weight was significantly lower in patients delivering SGA neonates compared with controls (P < .001). CONCLUSION: Second-trimester AF or maternal serum interleukin-10 levels are not predictive of subsequent delivery of SGA infants.

Multiple external root resorption. Case report.

A case of a patient with multiple external root resorption affecting principally the molars and premolars is described. This case is unusual in that although both right and left molar and premolar teeth are involved, the resorption is worse on the left side and affects only the distal roots of the molars.

The bonding of an adhesive resin cement to single and combined adherends encountered in resin-bonded bridge work: an in vitro study.

Although resin-bonded bridges should ideally be bonded to enamel, abutment teeth may present with dentine or restorations at the bonding sites. This study assessed the influence of bonding to such adherends on bridge retention by using tensile bond strength measurements as the criteria for judgement. An adhesive resin cement (Panavia Ex) was bonded to single adherends of enamel, dentine, composite resin, glass ionomer or amalgam, and to combined adherends of enamel/dentine or enamel/restorative material. The bond strength to enamel (28 MPa) was comparable with that to composite resin (25 MPa), but significantly higher than to dentine (8 MPa), amalgam (8 MPa) and glass ionomer (13 MPa). When the bonding area was half enamel and half restorative material, the bond strength was only equivalent to that obtained when the entire bonding area consisted of restorative material, the less favourable adherend. A similar trend was observed with specimens of enamel/dentine. This indicated that the magnitude of the bond between the resin cement and combined adherends was limited by the strength of the bond to the less favourable adherend. It appears that extending a bridge retainer to cover exposed dentine, a glass-ionomer filling or an amalgam filling, could adversely affect the bridge retention.

Changing perceptions of the requirements of cavity preparations.

Perceptions of the requirements of cavity preparations have changed over the years. These have had a significant effect on undergraduate teaching at the University of Bristol Dental School, an explanation of which may help general dental practitioners in their quest for information on this important aspect of dental practice. A method is described for teaching undergraduate dental students cavity preparation in caries-free teeth, based upon the position, shape and extent of imaginary carious lesions. Scale diagrams of teeth are used, on which imaginary caries at the amelodentinal junction has been marked. The students are instructed to apply the principles of cavity preparation to equivalent, but caries-free, teeth in the laboratory. 'Outline forms' and other predetermined cavity shapes are not taught. Dental practitioners may find it appropriate to apply similar thinking to cavities they prepare in everyday practice, in an endeavour to avoid the unnecessary removal of tooth tissue that would be better retained.

Tensile strength of enamel-resin-metal joints.

This study evaluated the tensile strength of enamel-resin-metal joints formed with four adhesive systems for attaching resin-bonded FPDs. Groups of 10 cast alloy cylinders were blasted with 50 microns alumina, washed, and prepared for bonding according to the resin as follows: (1) Panavia Ex with no treatment, (2) Super-Bond oxidized for 2 minutes with potassium permanganate in sulphuric acid, (3) Conclude electrolytically etched, and (4) ABC conditioned with primer. The cylinders were bonded to etched human enamel and after 24 hours in water at 37 degrees C the tensile strengths of the joints were recorded. Joint failure was examined under a stereomicoscope and a scanning electron microscope. The results demonstrated that the adhesive system influenced the tensile strength and mode of failure of the joints.

The bonding of glass-ionomer cements to dental amalgam.

Clinicians are frequently confronted with the problem of ditched amalgam restorations. Materials which develop strong bonds to amalgam and tooth substance appear to be suitable for repair of such restorations and eliminate the need for complete replacement. This study evaluated the bond strengths of three glass-ionomer cements to amalgam made from conventional and high copper alloys. It was found that the bond strength values to amalgam were comparable with those to enamel and significantly higher than those to dentine. All bonds to the high copper amalgam failed in a cohesive mode; for the conventional amalgam, failure was either of the adhesive or cohesive type.