Maternal influences on thiamine status of walleye Sander vitreus ova.

Concentrations of the various forms of thiamine (vitamin B(1) ) were determined in walleye Sander vitreus ova from three central North American lakes. Total thiamine concentrations in ova from Lake Winnipeg S. vitreus were approximately three times greater (mean 12 nmol g(-1) ) than in those from Lakes Erie or Ontario. The percentage of thiamine in the active form (thiamine pyrophosphate, TPP) was highest in Lake Ontario ova (mean 88%) and lowest in those from Lake Winnipeg (mean 70%). Neither ova total thiamine concentration nor per cent ova thiamine as TPP showed any consistent relationships with maternal age, size, morphometric condition, somatic lipid concentrations or liver lipid concentrations. Ova total thiamine concentration, however, was negatively related to ovum size in some populations, as well as among populations, and was positively related to liver total thiamine concentration. Maternal transfer of thiamine to ova appears to be independent of female ontogenetic or conditional state in S. vitreus.

Neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension.

The aim of this study was to determine whether neutrophil activation occurs in the fetal circulation in pregnancy-induced hypertension and to correlate this with evidence of neutrophil activation in the maternal circulation. Twenty-one normal pregnancies and 23 complicated by pregnancy-induced hypertension were studied in the third trimester. The mean length of gestation at delivery was significantly shorter (P less than .01) and the mean birth weight percentile was significantly lower (P less than .05) in the hypertensive group; otherwise the groups were comparable. Blood was obtained before cesarean delivery or established labor in the mothers and immediately after delivery from the umbilical vein. Plasma neutrophil elastase, which is released after neutrophil activation, was measured by radioimmunoassay as a marker for neutrophil activation. The mean (+/- standard error) concentration of neutrophil elastase in maternal plasma in the hypertensive group (35.9 +/- 4.7 ng/mL) was significantly higher than in the normal group (20.8 +/- 0.87 ng/mL) (P less than .005). The concentration of neutrophil elastase in umbilical venous plasma was not significantly different between the normal and hypertensive groups. However, significantly higher concentrations of neutrophil elastase were found in the umbilical venous plasma of pregnancies delivered vaginally compared with those delivered by cesarean (P less than .05) regardless of diagnosis. There was no correlation between maternal venous and umbilical venous plasma neutrophil elastase concentrations, birth weight percentile, plasma urate, or platelet count. These data suggest that neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension where it may contribute to vascular damage and dysfunction in areas such as the placental bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased neutrophil activation in diabetic pregnancy and in nonpregnant diabetic women.

Human neutrophil elastase may be a mediator of vascular damage, and enhanced neutrophil reactivity could contribute to the susceptibility of pregnant diabetic women to vascular complications. Elevated plasma levels of neutrophil elastase will reflect neutrophil activation in vivo. The aim of this study was to determine whether neutrophil activation occurs in uncomplicated diabetic pregnancy. We studied 30 normal nonpregnant women, 20 nonpregnant diabetic women, 32 nondiabetic women with normal pregnancies, and 17 insulin-requiring pregnant diabetic patients. Plasma neutrophil elastase was measured by radioimmunoassay. There was a significantly higher concentration of plasma neutrophil elastase in normal pregnant women compared with the nonpregnant group (P less than .001). The nonpregnant diabetic group had significantly higher concentrations than the normal nonpregnant group (P less than .002). The pregnant diabetic group had significantly higher concentrations than the nonpregnant diabetic group (P less than .001) and the normal pregnant group (P less than .05). The high concentrations of plasma neutrophil elastase may contribute to the greater sensitivity of pregnant diabetic patients to vascular complications.

The measurement of the main PGE metabolite, 13,14-dihydro-15-keto prostaglandin E by radioimmunoassay using methyl oxime stabilization.

The measurement of 13,14-dihydro-15-keto prostaglandin E2 [PGEM] is complicated by the artefactual formation of compounds of the corresponding A series which are reactive towards protein. Existing methods of assay depend on the deliberate dehydration to the 'A' form followed by cyclization in alkaline solution to a bicyclic derivative which is stable and can be measured by radioimmunoassay. We report an alternative approach using methyl oximation of the 9- and 15-keto groups which confer stability on the molecule. This derivatization is simple and does not involve an active intermediate such as those of the PGA series. The antiserum for radioimmunoassay is raised against the methyl oxime form. The label is the methyl oxime of PGEM coupled to a tripeptide Pro-gly-tyr through the nitrogen in the proline ring. This is a linkage distinct from that used to raise the antiserum and thus is not preferentially recognized over the endogenous analyte; this results in a high sensitivity assay. The results correlated well with those from the bicyclic assay when both assays were used to measure the same samples of peripheral blood from women receiving a sustained release PGE pessary for ripening the cervix. The technique provides a rapid and reliable method for determining prostaglandin E metabolites.

Intraoperative stents to rehabilitate severely stenotic pulmonary vessels.

BACKGROUND: Patch enlargement of severe branch pulmonary artery stenosis (PAS) or pulmonary vein ostial stenosis (PVS) can be technically challenging. Recurrences are common and exposure may require long periods of cardiopulmonary bypass (CPB). METHODS: Since 1993, we performed 31 procedures on 27 patients with endovascular stents placed intraoperatively under direct surgical vision: 22 patients with tight PAS and 5 patients with PVS. Selection for intraoperative (vs catheterization laboratory) stent placement was prompted by: (1) the need for a concomitant cardiac surgical procedure (16 cases); (2) limited vascular access for catheterization laboratory stent placement (11 cases); or (3) "rescue" of patients with complications after attempted placement of stents (4 cases). RESULTS: In this group of very complex and challenging patients there were 5 hospital deaths (hospital survival, 81%). Follow-up of survivors has ranged from 1 month to 7 years (mean 2.8 +/- 1.7 years). There have been 3 late deaths (late "series" survival, 70%). No complication or death was related to stent placement. Surviving patients have had significant clinical improvement. Mean pulmonary gradient (postoperative vs preoperative echo) has fallen in all survivors and has decreased from a mean of 66 mm Hg preoperatively to 28 mm Hg postoperatively (p = 0.01). All pulmonary arteries are appreciably enlarged and will be easier to deal with at a later date if necessary. One patient (DORV, HLHS ) with pulmonary vein stents has gone on to a successful Glenn procedure. The other two surviving patients with PV stents have occlusion of their proximal PVs on follow-up catheterization; thus only 1 of 5 patients with stents for PVS has had a successful outcome. Four patients have had repeat surgery. Stents have produced no impediment to subsequent surgical procedures, and the pulmonary arteries were easy to work with. CONCLUSIONS: Intraoperative stenting provides an attractive option for "rehabilitation" of pulmonary vessels. Direct vision insertion on CPB is extremely quick and immediately effective, limiting the CPB exposure required to treat this problem. Once stented, vessels remain open and are amenable to future surgical intervention as necessary. Outcome is better for patients with PAS versus those with PVS.

Intra- and interpopulation variability in maternal transfer of mercury to eggs of walleye (Stizostedion vitreum).

Mercury concentrations were determined for unfertilized eggs from seven walleye populations and for muscle and liver tissue from three of these seven populations in Canada and the United States. Female walleye transferred very little of their body methylmercury burden to their eggs. Methylmercury concentrations in eggs were 1.1-12% of those in muscle, and methylmercury burdens in eggs represented only 0.2-2.1% of the total body burden. Egg methylmercury as a percentage of total mercury increased with maternal length across populations. Percent methylmercury also increased with egg total mercury concentration but the slope of this relationship varied among populations. Egg methylmercury concentration increased with female age, and both muscle and liver methylmercury concentrations. Egg methylmercury concentration was also affected by female length at age but the effect of this relationship varied among populations. Mean predicted egg methylmercury concentrations (ng g(-1) dry) of 8-year-old, 550-mm females for the seven populations were as follows: Clay Lake, 796; Lake Superior, 24.3; Lake Winnipeg, 16.3; Lake Erie, 11.8; Primrose Lake, 8.76; Lake Manitoba, 7.32; Waconda Lake, 6.69.

Effects of environmental and maternally derived methylmercury on the embryonic and larval stages of walleye (Stizostedion vitreum).

The effects of environmental and maternally derived methylmercury (MeHg) on the embryonic and larval stages of walleye (Stizostedion vitreum) were investigated using eggs collected during two successive spawning seasons. Eggs were collected from fish in a mercury (Hg)-polluted environment (Clay Lake, Ontario, Canada), and from fish in two relatively pristine lakes (Lakes Manitoba and Winnipeg, in the province of Manitoba). Both bioaccumulation of Hg into muscle and its mobilization into eggs was significantly higher in Clay Lake females. Maternal muscle MeHg concentration was positively correlated with female length and egg MeHg was positively correlated with muscle MeHg concentration in all three populations. Hatching success of eggs from all three stocks declined significantly with increasing waterborne MeHg (0.1-7.8 ng l-1). Hatching success was not significantly affected by egg MeHg concentration. Embryonic heart rate declined with increasing waterborne MeHg concentration, but larval growth was not affected. Occurrence of larval deformities was negatively correlated with size of female, but was not significantly correlated with MeHg in either eggs or water. Larval MeHg was positively correlated with the concentrations of MeHg in eggs demonstrating transmission of MeHg from females. Uptake of ambient MeHg was higher in larvae exposed to higher waterborne MeHg concentrations.

Antenatal screening for haemoglobinopathies in primary care: a cohort study and cluster randomised trial to inform a simulation model. The Screening for Haemoglobinopathies in First Trimester (SHIFT) trial.

OBJECTIVES: To assess the effectiveness, cost-effectiveness, acceptability and feasibility of offering universal antenatal sickle cell and thalassaemia (SCT) screening in primary care when pregnancy is first confirmed and to model the cost-effectiveness of early screening in primary care versus standard care. DESIGN: A population-based cohort study, cluster randomised trial and refinement of a published decision model. SETTING: Twenty-five general practices from two UK primary care trusts (PCTs) in two inner city boroughs with a high proportion of residents from minority ethnic groups. PARTICIPANTS: Practices were considered eligible if they agreed to be randomised and they were able to provide anonymous data on all eligible pregnant women. Participants were at least 18 years old and consented to take part in the evaluation. INTERVENTIONS: Practices were allocated to intervention, using minimisation and stratifying for PCT and number of partners at the practice, as follows: screening in primary care with parallel father testing (test offered to mother and father simultaneously; n = 8 clusters, 1010 participants); screening in primary care with sequential father testing (test offered to father only if mother identified as carrier; n = 9 clusters, 792 participants); and screening in secondary care with sequential father testing (standard care; n = 8 clusters, 619 participants). MAIN OUTCOME MEASURES: Data on gestational age at pregnancy confirmation and screening date were collected from trial practices for 6 months before randomisation in the cohort phase. The primary outcome measure was timing of SCT screening, measured as the proportion of women screened before 70 days' (10 weeks') gestation. Other outcomes included: offer of screening, rates of informed choice and proportion of women who knew the carrier status of their baby's father by 77 days (11 weeks). RESULTS: For 1441 eligible women in the cohort phase, the median [interquartile range (IQR)] gestational age at pregnancy confirmation was 7.6 weeks (6.0 to 10.7 weeks) and 74% presented in primary care before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR 12.6 to 18.0 weeks). Only 4.4% were screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7 to 9.3 weeks). In the intervention phase, 1708 pregnancies from 25 practices were assessed for the primary outcome measure. Completed questionnaires were obtained from 464 women who met eligibility criteria for the main analysis. The proportion of women screened by 10 weeks (70 days) was 9/441 (2%) in standard care, compared with 161/677 (24%) in primary care with parallel testing, and 167/590 (28%) in primary care with sequential testing. The proportion of women offered screening by 10 weeks (70 days) was 3/90 (3%) in standard care (note offer of test ascertained for questionnaire respondents only), compared with 321/677 (47%) in primary care with parallel testing, and 281/590 (48%) in primary care with sequential testing. The proportion of women screened by 26 weeks (182 days) was similar across the three groups: 324/441 (73%) in standard care, 571/677 (84%, 0.09) in primary care with parallel testing, and 481/590 (82%, 0.148) in primary care with sequential testing. The screening uptake of fathers was 51/677 (8%) in primary care with parallel testing, and 16/590 (3%) in primary care with sequential testing, and 13/441 (3%) in standard care. The predicted average total cost per pregnancy of offering antenatal SCT screening was estimated to be 13 pounds in standard care, 18.50 pounds in primary care with parallel testing, and 16.40 pounds in primary care with sequential testing. The incremental cost-effectiveness ratio (ICER) was 23 pounds in primary care with parallel testing and 12 pounds in primary care with sequential testing when compared with standard care. Women offered testing in primary care were as likely to make an informed choice as those offered screening by midwives later in pregnancy, but less than one-third of women overall made an informed choice about screening. CONCLUSIONS: Offering antenatal SCT screening as part of pregnancy-confirmation consultations significantly increased the proportion of women screened before 10 weeks (70 days), from 2% in standard care to between 16% and 27% in primary care, but additional resources may be required to implement this. There was no evidence to support offering fathers screening at the same time as women. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00677850.

Hypoxic inhibition of human myometrial contractions in vitro: implications for the regulation of parturition.

BACKGROUND: Insufficient tissue oxygenation is a likely contribution to weak, inco-ordinate human uterine contractile activity characteristic of prolonged, dysfunctional labour. However, the direct effects of hypoxia on human myometrial contractility has, surprisingly, not yet been detailed. Therefore, we report the influence of hypoxia on spontaneous and agonist-induced carbachol, prostaglandin (PGF2alpha), and oxytocin contractions of myometria from nonpregnant and pregnant women. MATERIALS AND METHODS: Uterine biopsies were obtained from pregnant women at term undergoing elective Caesarean section and nonpregnant women undergoing hysterectomy. Myometrial strips were equilibrated at 37 degrees C in normoxic physiological salt solution (95% air/5% CO(2)) and the influence of hypoxia (95% N(2)/5% CO(2)) on contractility was investigated. RESULTS: Hypoxia resulted in a significant reduction in spontaneous contractile function; nonpregnant tissue was less resistant to the deleterious effects of hypoxia. Agonist-induced contractions, while being more resistant to hypoxia than spontaneous contractions, were also significantly inhibited. In myometria of pregnant women the PGF2alpha- or oxytocin-induced contractility was more resistant to hypoxia than carbachol. Finally, the inhibitory actions of hypoxia were exacerbated with repeated oxytocin administration with a more severe effect on contractile integral than on initial phasic contraction amplitude. CONCLUSIONS: We detail, for the first time, the effects of hypoxia on contractility of human myometria from nonpregnant and pregnant women. Physiologically important uterotonic agents are more resistant to the effects of hypoxia than spontaneous contractions although repeated stimulation with oxytocin during hypoxia results in progressively less force. The results indicate that if significant hypoxia occurs in vivo then it is a likely contributory factor to the pathways underlying prolonged dysfunctional labour.

Could some fetocides be avoided by more prompt referral after diagnosis of fetal abnormality?

When a fetal abnormality has been diagnosed, a woman may be offered termination of pregnancy. It is important that delays in the assessment process are avoided, as after 21 weeks' gestation fetocide must be performed as part of the termination, with only a few rare exceptions. To determine whether preventable delays in the assessment of suspected fetal abnormalities are occurring, a retrospective review of all stillbirths resulting from termination of pregnancy in 1998 and 1999 in the North Western Region of England was conducted. There were 47 terminations of pregnancy after 24 weeks gestation. Of these, 43 cases had intracardiac potassium chloride fetocide before induction of labour. One of the 47 women was not referred to the tertiary referral centre; 39 women were referred within 1 week of the diagnosis of an abnormality, but in seven cases referral was delayed for more than 2 weeks. Inappropriate and preventable delays are occurring. In some cases this may mean that a woman has to undergo fetocide, which could have been avoided had she been referred to a tertiary centre more promptly.

Transhepatic catheterization using ultrasound-guided access.

The efficacy and safety of ultrasound guidance to obtain transhepatic access for cardiac catheterization were investigated in this study. The transhepatic route for access to perform cardiac catheterization has become an acceptable alternative when conventional routes of access have failed. However, the use of ultrasound to guide transhepatic access has not been reported in the literature. We performed a retrospective chart review. Patient characteristics, indications for catheterization, procedures performed, and complications were recorded. All patients who underwent transhepatic cardiac catheterization at Duke University Medical Center were included in this study. Eight patients underwent 12 catheterizations. The median age was 5.3 years (range, 9 months to 13 years) and median weight 18.7 kg (range, 7.1-44.8 kg). Seven catheterizations were diagnostic and 5 were interventional. There were no complications. Transhepatic access with ultrasound guidance is a safe and effective option for obtaining venous access for cardiac catheterization.

Amplatzer septal occluder closure of secundum atrial septal defects in the presence of persistent left superior vena cava to coronary sinus.

Secundum atrial septal defects (ASDs) are routinely closed using transcatheter devices. In patients with left superior vena cava (LSVC) draining to the coronary sinus (CS), the device must not obstruct CS drainage. We report five cases of successful ASD device closure without obstructing flow from the LSVC or dilated CS.

Plasma prostaglandin metabolite concentrations in normal and dysfunctional labour.

OBJECTIVE: To determine the concentrations of the metabolites of prostaglandin E2 (PGEM) and of prostaglandin F2 alpha (PGFM) prior to the onset of labour and during spontaneous labour, and to correlate the changes in concentrations of these metabolites with labour outcome. DESIGN: Longitudinal study throughout labour. SETTING: Labour ward of a large maternity unit. SUBJECTS: Seven primigravid and 11 parous women in the late third trimester with no signs of labour, and 17 primigravid and 11 parous women in spontaneous labour. INTERVENTIONS: Six of the primigravid women required augmentation with oxytocin because of dysfunctional labour. RESULTS: Before labour, parous women had significantly higher concentrations of both PGEM (P < 0.007) and PGFM (P < 0.006) compared with primigravid women. During labour, PGFM concentrations were significantly higher in both primigravid (P < 0.0002) and parous (P < 0.0001) women compared with the concentrations of these metabolites in women not in labour; the same was true for PGEM in primigravid (P < 0.003) but not in parous (P = 0.1) women. There was a small but significant increase (P < 0.02) in PGEM as labour progressed in both the normal groups. Amniotomy was associated with a significant increase in PGFM in primigravid and parous women (P < 0.002 and P < 0.009, respectively). The concentration of PGFM one hour following amniotomy correlated inversely with the amniotomy to delivery interval in both the normal primigravid (r = -0.624; P = 0.04) and the parous (r = 0.745; P = 0.021) groups. Women with dysfunctional labour showed no significant rise in PGEM or PGFM. Their PGFM concentrations were significantly lower than those seen in normal labour (P < 0.05). The concentration of PGFM in cord blood was significantly higher (P < 0.0001) in the parous women who laboured than in women delivered by elective caesarean section. There was no difference in the corresponding concentrations of PGEM (P = 0.9). CONCLUSIONS: These data show that spontaneous labour is associated with increased concentrations of prostaglandin metabolites in the maternal plasma, and are consistent with PGF2 alpha being an important stimulator of uterine contractility, with a relative deficiency of PGF2 alpha being associated with dysfunctional labour.

Transcatheter occlusion of the patent ductus arteriosus: use of the retrievable coil device.

The Cook Retrievable Embolization Coil has been designed to improve delivery and positioning during coil embolization of the patent ductus arteriosus (PDA). We report our experience with the use of this new technique. Twenty-eight patients underwent coil embolization of a PDA using the retrievable system. The median patient age was 4.5 years (range, 2 months to 33 years), median weight 17.2 kg (range, 3.1-100 kg). The mean minimum diameter was 1.1 mm (range, 0.3-3.8 mm). One or two Cook Retrievable Embolization Coils were implanted in each PDA. Successful delivery was achieved in 27 cases. There was no shunt by angiography in 19 of the patients (70%). Color echocardiography documented no shunt in 13 of 17 patients (77%). The retrievable coil system represents a successful method of PDA occlusion with good control of coil positioning and delivery.