Umbilical artery Doppler in relation to placental pathology and FV Leiden in pregnant women and their offspring.

OBJECTIVE: Abnormal umbilical artery blood flow has been implicated in pregnancy complications and fetal demise. Its relation to histopathological changes in the placenta and to maternal or fetal thrombophilia is less well understood. The aim of this study was to evaluate the relation between umbilical artery Doppler findings, placental histopathology, and maternal and fetal coagulation factor V Leiden (FVL) status. METHODS: Two previous studies on FVL in pregnancy made the placentas of 25 women with maternal FVL carriership and 43 randomly selected non-carriers available for a histopathological examination. Umbilical artery Doppler velocimetry was performed on 54 women in late pregnancy. RESULTS: Abnormal umbilical artery Doppler velocimetry was associated with an approximately sevenfold increased risk of fetoplacental thrombotic vasculopathy (odds ratio [OR]: 7.5, 95% confidence intervals [CI]: 1.3-44.3), ischemic lesions (OR: 7.5, 95% CI: 1.2-46.1) and fetal carriership of FVL (OR: 8.2, 95% CI: 1.5-43.5), but not maternal FVL. Fetal FVL carriership was also associated with a sevenfold increased risk of ischemic lesions (OR: 6.7, 95% CI: 1.3-35). CONCLUSIONS: Our results indicate that the fetal - not the maternal - FVL carriership matters regarding the umbilical artery blood flow and placental pathology, which might explain some of the heterogeneity of studies.

Uterine venous blood flow in normal and complicated pregnancies: a methodological study.

OBJECTIVE: To investigate the possibility of recording Doppler flow signals from the maternal uterine veins (UtVs) during pregnancy and to assess the relationship between UtV signals and other Doppler parameters as well as pregnancy outcomes. METHODS: Transabdominal Doppler ultrasound examination of the UtVs on both sides of the uterus was performed in 40 normal and 44 high-risk singleton pregnancies at 23-39 weeks' gestation. The UtV was identified using color Doppler imaging and the flow velocity signals of the UtV and uterine artery (UtA) were recorded. Morphological examination of the placenta was carried out in 45 of the pregnancies (14 uncomplicated and 31 high-risk pregnancies). RESULTS: Flow-velocity signals of the UtVs were recorded from at least one side of the uterus in all patients (success rate of 81 and 89% for the right and left UtV, respectively). Three types of flow-velocity pattern were identified: continuous non-pulsatile flow (Type I, n = 70), pulsatile flow with a notch touching the zero line (Type II, n = 6) and pulsatile flow with absent flow signals for part of the heart cycle (Type III, n = 8). The UtA pulsatility index was significantly higher in women with UtV Types II and III than in those with UtV Type I (P = 0.039). Similarly, UtV Types II and III were more often found in pregnancies with bilateral UtA notching (P = 0.013) and with UtA score 3-4 (P = 0.024) than in those with normal UtA. No statistically significant association was found between the UtV flow pattern and abnormal histopathological findings in the placenta, or between the UtV and umbilical artery findings. CONCLUSION: It is possible to record Doppler signals from the UtVs in the late second and third trimesters of pregnancy. Pulsatile flow-velocity patterns of the UtVs are associated with abnormal UtA Doppler findings.

Structural heart defects associated with an increased nuchal translucency: 9 years experience in a referral centre.

OBJECTIVE: To investigate the congenital heart disease (CHD) found in association with an increased nuchal translucency (NT) at 11-14 weeks of gestation in chromosomally normal and abnormal fetuses. METHODS: Patients referred from January 1998 until May 2007 with an increased NT (> or = 95th percentile) where CHD was diagnosed were included. Chromosome analysis, fetal and postnatal echocardiography were performed. A postmortem examination followed pregnancy termination when possible. RESULTS: Major CHD was identified in 68 of 967 fetuses with an increased NT (median NT 4.8 mm, range 2.5-22 mm). Major CHD was found in 34 of 693 fetuses (4.9%) with a normal karyotype and increased NT (median 5.2 mm, range 2.5-9.6 mm). CHD frequency increased from 1.9%, with NT between 2.5 and 3.5 mm, to 27.7% when NT was > or = 6.5 mm. Septal defects predominated (20%) when NT was < or = 3.5 mm. With NT > 3.5 mm an equal distribution of CHD types was seen. Major CHD was identified in 34 of the 274 fetuses with an abnormal karyotype and increased NT (median 4.2 mm, range 2.5-22 mm). CONCLUSIONS: A variety of CHD is associated with an increased NT in the first trimester of pregnancy. Conotruncal defects, branchial arch derivative defects, left and right obstructive lesions (inflow and outflow) and shunts were seen.

Vascular mechanical properties and endothelial function in pre-eclampsia with special reference to bilateral uterine artery notch.

OBJECTIVES: To assess whether women with pre-eclampsia (PE) have different properties of the blood vessel wall compared to healthy pregnant controls. Further, to evaluate endothelial function and vascular mechanical properties in women with PE with special regard to its association with bilateral uterine artery notch and placental histopathology. PARTICIPANTS: Some 57 Caucasian pregnant women: 23 with uncomplicated pregnancies and normal uterine artery Doppler, and 34 with PE, the PE group comprising 2 subgroups according to the presence (n=20) or absence (n=14) of bilateral uterine artery notches. METHODS: Ultrasonic echo-tracking assessed the elastic properties of the common carotid artery, abdominal aorta and popliteal artery. Flow-mediated dilatation (FMD) of the brachial artery was measured by ultrasonography. Histopathological examination of the placenta was carried out in 46 pregnancies: 18 uncomplicated pregnancies, 15 with PE with bilateral notch, and 13 with PE without bilateral notch. RESULTS: There were no significant differences in carotid, aortic or popliteal vessel wall stiffness either between women with PE and controls or within the PE group. FMD was significantly lower in women with PE than in controls (p=0.03). The lowest FMD was observed in pre-eclamptic women with bilateral uterine artery notches 9.5% (SD: 5.3) compared to 11.6% (SD: 5.4) in pre-eclamptic women without bilateral uterine artery notch, and 13.4% (SD: 4.0) in controls (p=0.01). Bilateral uterine artery notching was significantly associated with a lower FMD (OR: 0.87; 95% CI: 0.77-0.98). There were significantly more placentas with high ischaemic score in the bilateral notch group than in the group with PE and normal circulation. CONCLUSIONS: There were no differences in vessel wall stiffness between women with PE and healthy controls. Women with PE showed signs of endothelial dysfunction, significantly more pronounced in women with bilateral uterine artery notch. Bilateral uterine artery notch was associated with ischaemic pathology of the placenta. Notwithstanding, a significant number of placentas in the PE group failed to show noteworthy ischaemic or other morphological changes that could explain the role of the placenta in the development of PE.

Expression of matrix metalloproteinase-2 and mutant p53 is increased in hydatidiform mole as compared with normal placenta.

Matrix metalloproteinases (MMPs) are group of enzymes thought to play an important role in trophoblastic and tumor invasion. The aim of our study was to investigate the trophoblastic expression of MMPs and p53 in normal trophoblast and hydatidiform moles (HM). Paraffin sections of 45 specimens, including 14 complete hydatidiform moles (CM), 15 partial hydatidiform moles (PM), 8 atypical partial hydatidiform moles (aPM), and 8 controls were selected. Classification of HM was established on histologic criteria and supported by the DNA ploidy results. Tissue sections from each case were immunostained with monoclonal antibodies, cytokeratin-7, MMP-2, MMP-9, tissue inhibitors of metalloproteinases (TIMP)-1, and p53 wild type (p53wt) and mutant types (mutp53). Staining for cytokeratin-7 revealed a positive reaction in 93% of the samples. MMP-2 was mainly expressed in the syncytiotrophoblast of HM and found in 62% of aPM, 60% PM, and 93% CM. The mutp53 was mainly and focally expressed in syncytiotrophoblastic cells and was found in 63% of aPM, 80% PM, and 93% CM. Expression of MMP-2 and mutp53 was both significantly greater in HM vs control group (P < 0.05) and greater in CM vs PM and aPM (P < 0.05). No significant difference was observed for cytokeratin-7, MMP-9, TIMP-1, and p53wt between the HM subgroups and between HM and control group. MMP-2 and mutp53 are overexpressed in HM as compared with normal trophoblast and might participate in the invasive behavior of the HM.

Clinical correlation between adenosine deaminase activity and pre-eclampsia severity.

This study evaluated the relationship between the activity of the inflammatory indicator adenosine deaminase (ADA) in placental tissue and maternal and fetal (umbilical cord) plasma and the severity of pre-eclampsia. Maternal and umbilical vein whole blood and placental tissue samples were collected from women with normal pregnancies (n = 33) and patients with mild (n = 12) or severe (n = 17) preeclampsia. ADA activity was measured spectrophotometrically. Significantly increased ADA activity was detected in maternal and fetal plasma, and placental tissue in patients with mild and severe pre-eclampsia compared with normal pregnancies; there were no significant differences between the mild and severe cases. The presence of increased ADA activity in pre-eclampsia is consistent with activation of the inflammatory system in this condition. The increased ADA activity was related to the presence of the disease but not the severity of clinical symptoms. Neonatal outcome did not significantly correlate with observed ADA activity.

Intervilosite crónica masiva da placenta / Intervilositis crónica masiva de placenta / Massive chronic intervillositis of placeta

A intervilosite crónica massiva é uma patologia raras vezes diagnosticada na placenta, com uma incidência inferior a 0.5%. O exame histológico da placenta mostra uma infiltração massiva do espaço intervilositário por células inflamatórias, sem lesões de vilite crónica associadas. Estas alterações vão comprometer a função placentar originando um compromisso fetal que se manifesta sob a forma de atraso de crescimento fetal intra-uterino, parto pré-termo ou morte fetal. Descreve-se um caso clínico, ilustrativo deste tipo de patologia, referente a uma mulher de 31 anos, II gesta, O para, com antecedentes de morte fetal intra-uterina às 13 semanas de gestação em gravidez anterior, tendo registado na actual gravidez um valor elevado de alfa-feto-proteína às 16 semanas de gestação e morte fetal intra-uterina inesperada às 18 semanas. O exame histológico da placenta demonstrou a presença de uma intervilosite crónica massiva. Este caso realça, ainda, o valor do exame anátomo-patológico da placenta em todos os casos de morte fetal in-trauterina, e a sua importância para o diagnóstico da etiopatogenia e prognóstico de futuras gestações (AU)

La intervilositis crónica masiva es una patología de la placenta, raras veces diagnosticada, con una incidencia inferior al 0,5 0/0. El examen histológico de la placenta muestra una inflamación masiva del espacio intervillositario, por células inflamatorias, sin lesiones de vellosidades crónicas asociadas. Estas alteraciones van a comprometer la función placentaria, originando un compromiso fetal que se manifiesta en una forma de retraso del crecimiento intrauterino, parto pretérmino o muerte fetal. Se describe un caso clínico ilustrativo de este tipo de patología, referente a una mujer de 31 años, secundigestante y primípara, con antecedentes de muerte fetal intrauterina a las 13 semanas de gestación en el embarazo anterior. En este embarazo se registra un valor elevado de la alfa-fetoproteína a las 16 semanas y muerte inesperada a las 18 semanas de embarazo. El examen histológico de la placenta demostró una intervillositis crónica masiva. Este caso realza el valor del examen histológico de la placenta en todos casos de muerte fetal intrauterina y su importancia en el diagnóstico de la etiopatogenia y pronóstico de futuras gestaciones (AU)

Massive chronic intervillositis (MCI) is an infrequently recognized placental lesion which is reported in less than 0.5 0/0 of cases. MCI is characterized by prominent inflammatory infiltrate in the intervillous space in the absence of significant chronic villitis. MCI has been associated with poor pregnancy outcome, including intrauterine growth restriction, preterm delivery and intrauterine fetal death. We report such a case of a 31-year-old woman, gravida 2, para 0, with a past history of one intrauterine fetal death at 13 weeks pregnancy, who became pregnant, and an elevated maternal serum alpha-fetoprotein was noted at 16 weeks gestation. The intrauterine fetal death was diagnosed at 18 weeks gestation. Histological examination of the placenta demonstrated the presence of MCI. This case also underlines the importance of the routine histopathological examination of the placenta in all cases of intrauterine fetal death, in view of its importance in aetiological diagnostic and prognostic information for future pregnancy (AU)

Plasticity of the enteric nervous system in patients with intestinal neuronal dysplasia associated with Hirschsprung's disease: a report of three patients.

Intestinal neuronal dysplasia is a controversial form of dysganglionosis that has been described both as an isolated disorder and in association with Hirschsprung's disease. It has been blamed for the bad outcome of bowel function in patients operated on for Hirschsprung's disease. According to various authors, intestinal neuronal dysplasia could be a primary disorder or secondary to other diseases of the bowel. The aim of this study was to assess the plasticity of the enteric nervous system in patients with Hirschsprung's disease-associated intestinal neuronal dysplasia and its ability to evolve spontaneously to normal innervation patterns. Since we prospectively introduced the assessment of the enteric nervous system of the ganglionated bowel in patients operated on for Hirschsprung's disease, 31 patients have been operated on for Hirschsprung's disease in our institution between 1995 and 2002. Among these patients, nine suffered postoperatively from severe constipation and five from bouts of entocolitis. IND was found in eight of them. We studied the evolution of the innervation in three of these patients by repeated serial full-thickness biopsies of the colon. All three patients underwent a colostomy before or after the pull-through procedure. Histopathological assessment of the enteric nervous system was made with conventional acetylcholinesterase histochemistry, rapid acetylcholinesterase histochemistry and immunohistochemistry for the Protein Gene Product 9.5 and the antigen CD56. This evolution was compared with the clinical outcome of bowel function. In our three patients with Hirschsprung's disease-associated intestinal neuronal dysplasia, this form of dysganglionosis evolved to normal innervation patterns within a period ranging from 9 to 18 months. This evolution was accompanied by an improvement of bowel function in all. We conclude that Hirschsprung's disease-associated intestinal neuronal dysplasia can evolve to a normal innervation, at least under certain circumstances such as a colostomy. Specific histopathological techniques are required to assess accurately the enteric nervous system.

Abnormal vascular network complexity: a new phenotypic marker in hereditary non-polyposis colorectal cancer syndrome.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch cancer family syndrome I (LCFS1) and II (LCFS2)) is one of the most common hereditary cancer disorders. HNPCC results from dominantly inherited germline mutations in mismatch repair (MMR) genes, leading to genomic instability and cancer. No predictive physical signs of HNPCC are available to date. AIMS: Increased complexity in tumour associated vascular growth has been reported. Here, we tested the hypothesis that an increased vascular network complexity is a phenotypic marker for LCFS2. METHODS: Fourteen subjects from an LCFS2 kindred (gene carriers, n=5; non-carriers, n=9) and 30 controls were examined. Fractal dimension (D) at two scales (D (1-46), and D (1-15), tortuosity (minimum path dimension, Dmin), and relative Lempel-Ziev complexity (L-Z) of the vascular networks from the lower gingival and vestibular oral mucosa were measured. RESULTS: LCFS2 networks exhibited a significantly increased overall complexity at both larger (D (1-46): 1.82 (0.04) v 1.68 (0.08); p<0.0001) and smaller (D (1-15): 1.51 (0.11) v 1.20 (0.09); p<0.0001) scales, increased destructured randomness (L-Z: 0.77 (0.09) v 0.56 (0.03); p<0.0001), and decreased vessel tortuosity (DMIN: 1.02 (0.03) v 1.07 (0.04); p=0.0005) compared with control patterns. The vascular networks of LCFS2 gene carriers showed higher complexity at the smaller scale (D (1-15): 1.59 (0.12) v 1.47 (0.07); p=0.034), and higher destructured randomness (L-Z: 0.85 (0.11) v 0.73 (0.05); p=0.013) than those of non-carriers. CONCLUSIONS: Increased oral vascular network complexity is a previously unrecognised phenotypic marker for LCFS2, and is related to gene mutation carrier status.

Interstitial cells of Cajal are normally distributed in both ganglionated and aganglionic bowel in Hirschsprung's disease.

Surgery for Hirschsprung's disease is often complicated by post-operative bowel motility disorders. The impact of intestinal neural histology on the surgical outcome has been previously studied, but no information is available concerning the influence of the distribution of interstitial cells of Cajal (ICC) on these complications. These cells are considered to be pacemakers in the gastrointestinal tract. The aim of this study was to assess the distribution of ICC in the proximal segment of resected bowel in Hirschsprung's disease and confront these results with the clinical outcome. Using immunohistochemistry for light microscopy, we compared the pattern of distribution of ICC in the proximal segment of resected bowel in Hirschsprung's disease with that in normal colon. We correlated these results with the corresponding neural intestinal histology determined by CD56 and the protein gene product 9.5 immunohistochemistry. The distribution of ICC in the proximal segment of resected bowel is identical to that of normal colon, regardless of normal or abnormal colon innervation. ICC distribution does not seem to contribute to post-operative bowel motility disorders in patients operated for Hirschsprung's disease

Can the degree of retrograde diastolic flow in abnormal umbilical artery flow velocity waveforms predict pregnancy outcome?

OBJECTIVE: Reverse end-diastolic flow is the most pathological type of the umbilical artery flow velocity waveform. We aimed to investigate whether additional prognostic information can be obtained from umbilical artery waveforms in cases with reverse end-diastolic flow. SUBJECTS AND METHODS: Umbilical artery Doppler velocity waveforms from 44 fetuses with reverse end-diastolic flow were analyzed and the following parameters measured: the highest amplitude and the area below the maximum velocity curve of forward and reverse flow (A, B and C, D, respectively) and the duration of forward and reverse flow (Tc and Td, respectively). Ratios A/B, C/D and Tc/Td were calculated. The cut-off values for A/B, C/D and Tc/Td with the best predictive values for perinatal death were established with the help of receiver operating characteristics curves. The three curves were compared with each other. RESULTS: Of the three ratios, A/B and C/D had the best capacity to predict perinatal death. Both ratios had acceptable sensitivities, specificities and positive predictive values. In this regard, A/B and C/D were comparable. The cut-off values for A/B and C/D were 4.3 and 4.52, respectively. Survivors had I significantly higher A/B and C/D ratios than non-survivors (P = 0.0001 and 0.0003, respectively). Significantly more fetuses with A/B or C/D below the established cut-off values had pulsations in the venous system (P < 0.05). In fetuses with a gestational age < =210 gestational days the survival rate was significantly higher in those with A/B or C/D above the cut-off values (P = 0.03 and 0.003, respectively). CONCLUSIONS: The A/B or C/D ratio can be used for quantification of the reverse end-diastolic flow waveforms in the umbilical artery and may offer additional information to the evaluation of fetal condition.

Signs of platelet activation, but not lipid peroxidation, in fetal blood associated with functional and structural umbilicoplacental lesions in pregnancies complicated by impaired glucose metabolism.

OBJECTIVES: To study the influence of platelet activation and lipid peroxidation in fetal blood on umbilical vascular prostanoid synthesis and placental morphology in diabetic pregnancy. METHODS: The concentrations of thromboxane A2 (TxA2) and malondialdehyde (MDA) were determined in umbilical cord plasma in 21 women with diabetes mellitus/impaired glucose tolerance (DM/IGT) and ten healthy women. Segments from the umbilical artery and vein were incubated and prostacyclin (PGI2) and TxA2 metabolites were determined. Prostanoid synthesis was stimulated with calcium ionophore at a second incubation. Histological examination was carried out in samples from the umbilical cord, membranes and placental parenchyma. Non-parametric statistical analysis was used, with a two-tailed p < 0.05 considered statistically significant. RESULTS: Cord plasma TxA2, but not MDA, was higher among DM/IGT women (p = 0.07). There were indications that cord plasma TxA2, but not MDA, was positively correlated with vascular prostanoid synthesis and synthesis capacity. In the umbilical vein, both the basal and stimulated PGI2 production and the stimulated TxA2 production were lower in the DM/IGT group. Ischemic placental lesions were associated with a high TxA, and a low MDA concentration in cord plasma. CONCLUSIONS: Even in less severe forms of impaired glucose metabolism, disturbances in platelet activation significantly affect both biochemical and morphological vessel wall and tissue functions in the umbilicoplacental unit. This could indicate an abnormal programming of fetal cell functions and designate cases at increased risk of developing cellular and organ damage.

Blood velocity in the fetal vein of Galen and the outcome of high-risk pregnancy.

BACKGROUND: Pulsation in the flow velocity waveform in the umbilical vein is related to perinatal mortality but the flow velocity waveform in the fetal vein of Galen is normally even and without fluctuation. OBJECTIVES: To establish whether blood flow velocity pulsations in the vein of Galen in high-risk pregnancies are related to outcome. STUDY DESIGN: The vein of Galen was located by colour Doppler ultrasound in 102 pregnancies complicated by severe pregnancy-induced hypertension. The blood velocity waveform was recorded by pulsed Doppler within 2 days of delivery and the presence pulsations related to pregnancy outcome, including emergency operative intervention and neonatal distress. Umbilical artery and vein and uterine artery blood flow velocity waveform were also recorded at the same time. The clinicians managing the women were unaware of the venous flow results. RESULTS: Pulsation were present in the vein of Galen in 68 cases and in the umbilical vein in 21. Both were significantly related to adverse outcome. Pulsations in the vein of Galen were seen in all seven perinatal deaths. CONCLUSIONS: Since umbilical venous pulsation are a late sign of fetal compromise, and pulsations in the vein of Galen seem to appear earlier, thus being an intermediate sign of fetal compromise that might be of great value for fetal surveillance.

Expression of CD44 and its isoforms in the fetal neuroblasts.

CD44 is a polymorphic transmembrane glycoprotein that exists as multiple isoforms resulting from alternative splicing and posttranslational modifications. Enhanced expression of CD44 has been correlated to the tumorigenicity and metastatic behavior in different malignant tumors. In contrast, human neuroblastomas exhibit an inverse correlation between CD44 expression and tumor malignancy. To determine whether there is a CD44 silencing in sympatho-adrenal precursors as a possible explanation for the down-regulation of CD44 in neuroblastomas, the expression of standard CD44H and v6, v7, v7v8, or v10 isoforms was analyzed by immunohistochemistry in human adrenal glands of 14- to 20-week-old gestational age fetuses. All of the fetal neuroblasts localized in the adrenal gland parenchyma and migrating from the sympathetic nerve chain into the fetal adrenal cortex strongly expressed CD44H but none of the CD44 isoforms could be detected in these cells. In contrast, a strong expression of CD44v7 and v6 was detected in the fetal adrenal cells. These results indicate that, as for many other cell types, the CD44H expressed by fetal neuroblasts may contribute to controlling their migration into the adrenal medulla and that the down-regulation of CD44H in neuroblastoma cells should be explained by mechanisms other than the fetal suppression of CD44H expression in their normal counterparts.

Assessment of the colon innervation with serial biopsies above the aganglionic zone before the pull-through procedure in Hirschsprung's disease.

Different types of colonic dysganglionosis, and in particular intestinal neuronal dysplasia (IND) have been blamed for certain postoperative complications after surgery for Hirschsprung's disease (HD). We prospectively assessed colon innervation above the aganglionic zone (AZ) before proceeding to pull-through (PT) in order to rule-out IND as a cause of those complications. We first used a two-stage procedure (TSP): Full-thickness biopsies were harvested above the AZ and a colostomy was established during a first stage. Biopsies were assessed postoperatively with conventional acetyl-cholinesterase (AChE) histochemistry and immunohistochemistry for protein gene product 9.5 (PGP 9.5) and antigen CD56 (CD56). Biopsies were repeated after 6 months if IND was found. When the innervation was normal, the PT was performed during a second stage. Since having refined a rapid AChE reaction, we now use a single-stage procedure (SSP). Biopsies are harvested above the AZ and assessed intraoperatively with rapid AChE staining, proceeding to PT during the same stage when the innervation is normal. Four patients underwent the TSP; 3 had normal innervation above the AZ and subsequently underwent PT. In 1 patient serial biopsies revealed IND-like dysganglionosis; 9 months later, the innervation was normal in repeat biopsies and PT was undertaken. Eleven patients underwent the SSP. Biopsies were normal in 9 but showed unclassifiable forms of dysganglionosis in 2. As these changes were not typical for IND, all patients underwent PT in the same stage. Both patients had a poor outcome of bowel function that required a colostomy in 1 and daily saline irrigations in the other. IND was found in repeat biopsies made during the colostomy in the 1st patient and markedly hypertrophied nerves in the submucosa as well as ectopic nerve cells in the lamina propria in the proximal border of the pulled-through colon in the other. All 13 other patients have normal bowel function. The assessment of colon innervation above the AZ before proceeding to PT allows safer surgical treatment of HD. Intraoperative AChE staining is reliable, but due to the size and number of the biopsies, IND might be overlooked. Non classifiable dysganglionosis should thus be taken into account in the diagnosis and follow-up of the patients, as it may be clinically significant.

Molar pregnancy with a coexistent fetus after intracytoplasmic sperm injection. A case report.

BACKGROUND: Normal fertilization is usually considered to have occurred when two pronculei (2PN) and two polar bodies are observed. Exceptions are the single pronucleated zygote resulting from asynchronous pronuclei. CASE: A 29-year-old woman entered a program of intracytoplasmic sperm injection and embryo transfer because of her husband's oligoasthenoteratozoospermia. Two cleavage-stage embryos (four blastomeres, grade 1 and 2) were obtained from one fertilized oocyte containing distinct 2PN and the other a single pronucleus (1PN). At 15 weeks' gestation the patient developed severe preeclampsia requiring termination of the pregnancy. Histopathologic examination and DNA ploidy by image analysis were consistent with a twin pregnancy combining a complete hydatidiform mole and normal pregnancy. CONCLUSION: We hypothesize that this 1PN was at the origin of the hydatidiform mole. This case highlights the danger of transferring an embryo having 1PN.

Fetal varicella-herpes zoster syndrome in early pregnancy: ultrasonographic and morphological correlation.

We report a case of an intrauterine fetal infection by the varicella-herpes zoster virus following maternal varicella at 17 weeks' amenorrhea. Prenatal diagnosis of fetal infection was confirmed by serology and fetal damage by ultrasonography. Autopsy of the fetus showed multiorgan manifestation with disseminated foci of necrosis and microcalcifications, encephalitis and unilateral segmental skin scarring with an underlying hypoplastic fixed lower limb. The placenta showed a multifocal chronic villitis with multinucleated giant cells. The lesions included segmental anomalies and multiorgan damage.

Early neonatal brain injury in histologic chorioamnionitis.

The relation between clinical or histologic chorioamnionitis and early neonatal adverse neurologic outcome was investigated (n = 483). Histologic, but not clinical, evidence of chorioamnionitis was found to be a significant predictor of periventricular echodensity (odds ratio, 2.4; 95% CI, 1.8-3.2), echolucency (3.3; 1.9-5.6), ventriculomegaly (2.7; 1.8-4.2), intraventricular hemorrhage > or =3 (3.5; 2.4-5.2), and seizures (2.3; 1.4-3.7).

Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice.

BACKGROUND: Arterial relaxation is largely regulated by endothelial nitric oxide (NO). Its diminished activity has been associated with incipient atherosclerosis. We investigated the endothelium-dependent relaxation of aorta in apolipoprotein E-knockout (apoE-KO) mice exposed to single or repeated Chlamydia pneumoniae inoculation. METHODS AND RESULTS: Forty-eight apoE-KO mice, 8 weeks old, were inoculated intranasally with C pneumoniae (n=24) or saline (n=24) every 2 weeks over a 6-week period. Twenty mice (10 infected and 10 controls) were killed at 2 weeks and 6 weeks, respectively, after the first inoculation. The smooth muscle tone of aortic rings was measured in vitro at both time points. The norepinephrine-precontracted thoracic aortic rings were successively exposed to methacholine in the absence and presence of N:(G)-nitro-L-arginine methyl ester (L-NAME) and diclofenac. The methacholine-induced relaxation was attenuated in the infected mice at 6 weeks in both the absence and presence of L-NAME (P:<0.05 and P:<0.01, respectively). When administered together with L-NAME, diclofenac enhanced the relaxation of the L-NAME-pretreated aortas in infected mice at 2 weeks (P:<0.05) but not in noninfected mice. The relaxation response from infected mice tended to differ in the same manner at 6 weeks (P:<0.1). No intimal thickening was detected at either time point. CONCLUSIONS: C pneumoniae impairs arterial endothelial function, and the NO pathway is principally involved. Cyclooxygenase-dependent vasoconstricting products may also account for the infection-induced impaired relaxation. These findings further support the role of C pneumoniae infection in atherosclerosis development.