Monitoring and treatment of anti-D in pregnancy.

Prophylactic anti-D is a very safe and effective therapy for the suppression of anti-D immunization and thus prevention of haemolytic disease of the foetus and newborn. However, migration from countries with low health standards and substantial cuts in public health expenses have increased the incidence of anti-D immunization in many "developed" countries. Therefore, this forum focuses on prenatal monitoring standards and treatment strategies in pregnancies with anti-D alloimmunization. The following questions were addressed, and a response was obtained from 12 centres, mainly from Europe.

Erratum: Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study.

[This corrects the article DOI: 10.1093/eep/dvz023.][This corrects the article DOI: 10.1093/eep/dvz023.].

Epigenome-wide association of father's smoking with offspring DNA methylation: a hypothesis-generating study.

Epidemiological studies suggest that father's smoking might influence their future children's health, but few studies have addressed whether paternal line effects might be related to altered DNA methylation patterns in the offspring. To investigate a potential association between fathers' smoking exposures and offspring DNA methylation using epigenome-wide association studies. We used data from 195 males and females (11-54 years) participating in two population-based cohorts. DNA methylation was quantified in whole blood using Illumina Infinium MethylationEPIC Beadchip. Comb-p was used to analyse differentially methylated regions (DMRs). Robust multivariate linear models, adjusted for personal/maternal smoking and cell-type proportion, were used to analyse offspring differentially associated probes (DMPs) related to paternal smoking. In sensitivity analyses, we adjusted for socio-economic position and clustering by family. Adjustment for inflation was based on estimation of the empirical null distribution in BACON. Enrichment and pathway analyses were performed on genes annotated to cytosine-phosphate-guanine (CpG) sites using the gometh function in missMethyl. We identified six significant DMRs (Sidak-corrected P values: 0.0006-0.0173), associated with paternal smoking, annotated to genes involved in innate and adaptive immunity, fatty acid synthesis, development and function of neuronal systems and cellular processes. DMP analysis identified 33 CpGs [false discovery rate (FDR) < 0.05]. Following adjustment for genomic control (λ = 1.462), no DMPs remained epigenome-wide significant (FDR < 0.05). This hypothesis-generating study found that fathers' smoking was associated with differential methylation in their adolescent and adult offspring. Future studies are needed to explore the intriguing hypothesis that fathers' exposures might persistently modify their future offspring's epigenome.

Labeling of surface proteins of herpes simplex virus type 1 using a modified biotin-streptavidin system.

Methods of labeling surface proteins on herpes simplex virus (HSV) which have minimal effect on the biological activity of the virus are useful for the study of both the localization and function(s) of surface proteins. The present work describes a procedure using a water-soluble biotin compound, sulfo-NHS-biotin, which is unable to penetrate biological membranes and reacts with primary amines in proteins. Labeled proteins were detected by binding of [125I]streptavidin. Specific reaction with surface proteins was shown in Western blots using antibodies against selected proteins in the envelope or in the tegument. Proteins susceptible to iodination were also biotinylated, but the efficiency of labeling varied from one protein to another. As a result of freezing and thawing of the virus, as well as the manipulations involved in Ficoll gradient purification, internal proteins were labeled. The infectivity of the virus was reduced by approximately 40% after biotinylation. Labeled viruses were visualized by fluorescein isothiocyanate-conjugated streptavidin, and seen as distinct spots on the surface of the cells.

The herpes simplex virus type 1 particle: structure and molecular functions. Review article.

This review is a summary of our present knowledge with respect to the structure of the virion of herpes simplex virus type 1. The virion consists of a capsid into which the DNA is packaged, a tegument and an external envelope. The protein compositions of the structures outside the genome are described as well as the functions of individual proteins. Seven capsid proteins are identified, and two of them are mainly present in precursors of mature DNA-containing capsids. The protein components of the 150 hexamers and 12 pentamers in the icosahedral capsid are known. These capsomers all have a central channel and are connected by Y-shaped triplexes. In contrast to the capsid, the tegument has a less defined structure in which 11 proteins have been identified so far. Most of them are phosphorylated. Eleven virus-encoded glycoproteins are present in the envelope, and there may be a few more membrane proteins not yet identified. Functions of these glycoproteins include attachment to and penetration of the cellular membrane. The structural proteins, their functions, coding genes and localizations are listed in table form.

Retinal detachment in association with preeclampsia and abruptio placentae.

Retinal detachment is a rare complication of preeclampsia, eclampsia and abruptio placentae. We report a case of bilateral retinal detachment in association with severe preeclampsia complicated with abruptio placentae, intrauterine fetal death and disseminated intravascular coagulation. In obstetric complications, placental thromboplastin may release into maternal circulation and activate the extrinsic coagulation system with resultant disseminated intravascular coagulation. This may be responsible for choroidal ischemia and consequent serous retinal detachment.

A vascular approach to mild amnestic cognitive impairment: a pilot study.

OBJECTIVE: Mild cognitive impairment (MCI) is a subtle memory disorder not matching criteria for dementia. There is evidence for vascular comorbidity in several types of dementia. We hypothesized that neurovascular workup would detect a high degree of vascular disease in patients with MCI. MATERIALS AND METHODS: In cooperation with our memory clinic, patients with amnestic MCI were referred to our department for neurovascular investigation. The workup encompassed ultrasound examination with carotid duplex including Intima-Media-Thickness (IMT) measurement, and transcranial Doppler (TCD) including one-hour microemboli monitoring, cerebrovascular reactivity measurement and Bubble test. Cerebral MRI for the evaluation of vascular and white-matter lesions, brain atrophy, hippocampal volumes, and amyloid angiopathy was performed. RESULTS: Ten patients were included. Vascular risk factors were present in six patients. Four patients had atherosclerotic lesions, three classified as mild, and one as moderate carotid stenosis. IMT > 1 mm was found in two patients, with a maximum IMT of 1.11 mm. None of the patients with acceptable bone window had intracranial stenosis in TCD. Vasoreactivity was pathologically low in one patient. Permanent right-left shunt was found in three patients, of which one showed spontaneous cerebral microembolism. Hippocampal volume reduction and cortical atrophy were found in four patients. Chronic ischemic changes in MRI were present in one patient, and three patients had subcortical infarctions. Cortical infarctions, microbleeds, or amyloid angiopathy were not found. CONCLUSIONS: Pure amnestic MCI is probably less associated with cerebrovascular disease and may be more consistent with evolving Alzheimer's disease. However, vascular risk factors are common in these patients.

Effect of umbilical ring constriction on Wharton's jelly.

OBJECTIVE: The turgor of Wharton's jelly depends on osmotic and hydrostatic pressures. We tested the hypothesis that umbilical ring constriction has an impact on umbilical venous hemodynamics and thus on the volume of Wharton's jelly. METHODS: In a cross-sectional study of 237 low-risk singleton pregnancies, the cross-sectional area of the fetal end of the umbilical cord was determined using sonography at 20-41 weeks of gestation. The inner area of the two arteries and the vein was also measured and subtracted from the cord area to calculate the area of Wharton's jelly. Based on the Bernoulli equation, the degree of vein constriction at the umbilical ring was assessed using the blood velocity increment at the abdominal inlet. Regression analysis and SD-score statistics were used to construct mean values and to assess the effects. The dataset was also analyzed for gender-specific effects. RESULTS: The umbilical cord cross-sectional area increased with gestational age during the period 20-31 weeks, remaining essentially stable thereafter. The Wharton's jelly increased with gestational age from 20 until 31-32 weeks of gestation and remained at the same level for the rest of the pregnancy. At mid-gestation, on average 70% of the cord cross-sectional area was occupied by Wharton's jelly; at 31 weeks and later this value was 60%. Umbilical vein constriction was associated with reduced umbilical cord cross-sectional area and Wharton's jelly in female fetuses (P = 0.0007 and P = 0.003, respectively), but not in male fetuses. CONCLUSIONS: Under physiological conditions, umbilical ring constriction affects umbilical vein hemodynamics, with corresponding effects on the umbilical cord cross-sectional area and the amount of Wharton's jelly. Interestingly, the effects are gender-specific.

[Acute infectious myelitis]. / Infeksiøs akutt myelitt.

BACKGROUND: Acute myelitis is a clinical condition affecting the motor, sensor or autonomic function of the spinal cord. The etiology is often unknown, although a diversity of pathogens have been associated with acute myelitis. MATERIALS AND METHODS: Based on relevant literature we present an overview of the most important pathogens responsible for infectious acute myelitis in northern Europe, as well as recommendations regarding diagnostic guidelines. RESULTS: The pathogenic mechanisms are only partly known. Both replication of the pathogen, cellular defence mechanisms after invasion of the central nervous system, and the immune system seem to be important for the neurological damage. INTERPRETATION: Identification of a causative agent is important for the etiologic diagnosis and offers the possibility of specific treatment.

Blood flow and the degree of shunting through the ductus venosus in the human fetus.

OBJECTIVES: Our goal was to determine the degree of shunting through the ductus venosus in the human fetus and its possible association with fetal growth. STUDY DESIGN: Blood flow in the umbilical vein and the fetal ductus venosus was measured in 197 low-risk pregnancies in a cross-sectional ultrasonographic study at a gestational age of 18 to 41 weeks. The degree of shunting was compared to birth weight and ponderal index. RESULTS: The average fraction shunted through the ductus venosus was 28% to 32% at 18 to 20 weeks, decreased to 22% at 25 weeks, and reached 18% at 31 weeks (with wide ranges expressed in the 10th and 90th percentiles). Fetuses <10th percentile for birth weight had significantly more shunting (1.4%) than those >90th percentile (95% confidence interval, 0.1%-2.7%; P =.04). CONCLUSIONS: In the human fetus a higher proportion of umbilical blood is directed to the liver and less is shunted through the ductus venosus, in comparison with what has previously been shown in animal experiments.

The effect of vascular constriction on umbilical venous pulsation.

OBJECTIVES: Umbilical venous pulsation is an important sign of hemodynamic compromise, but is also found under normal physiological conditions. Mathematical modeling suggests that vascular compliance is a determinant for pulsation, and we tested this by studying velocity pulsation at three sites on the umbilical vein. METHODS: In a cross-sectional study of 279 low-risk pregnancies (20-40 weeks' gestational age) blood flow velocity in the umbilical vein was determined before, within and after the umbilical ring in the fetal abdominal wall, and the incidence and magnitude of pulsation (the difference between the maximum and minimum velocity during a pulse, and pulsatility index) were noted. Based on the fact that the vessel cross-sectional area is an important determinant of compliance, we measured the diameter and time-averaged maximum velocity to reflect variation in diameter and compliance at the three sites. RESULTS: The incidence of umbilical venous pulsation was higher at the umbilical ring in the abdominal wall (242/279, 87%, 95% CI 82-90) than in the cord (43/198, 22%, 95%CI 16-27) or intra-abdominally (84/277, 30%, 95% CI 25-36) (P < 0.001). When pulsation was observed intra-abdominally, the pulsatility was not different from that at the umbilical ring (P = 0.16). However, the lowest pulsatility was found in the cord vein (P < 0.0001), where the largest vein diameter was found. CONCLUSION: The high incidence of venous pulsation at the umbilical ring where diameter and compliance are low supports the suggestion that local compliance is an important factor influencing pulsation in fetal veins.

The development of high venous velocity at the fetal umbilical ring during gestational weeks 11-19.

OBJECTIVE: To determine the occurrence of high venous velocities at the umbilical ring in the normal early second trimester, based on the assumption that a narrow umbilical ring may cause obstruction and increased venous blood velocity at the abdominal wall. DESIGN: Cross-sectional study. SETTING: Hospital antenatal clinic. POPULATION: One hundred and one low risk singleton pregnancies specifically recruited for the study. METHODS: Ultrasound was used at 11-19 weeks to determine the diameter and velocity in the umbilical vein at the fetal end of the cord and at the inlet through the abdominal wall. Outcome measures 10th, 50th and 90th centiles were estimated for the time-averaged maximum velocity in the cord and at the abdominal inlet. The increase of velocity as the blood entered the abdominal wall was calculated in percent of the velocity in the cord. RESULTS: During weeks 11-12 there was hardly any difference between blood velocity in the umbilical vein at the umbilical ring and that in the cord. From week 13 onwards it was increasingly common to find blood acceleration at the umbilical ring of 50-500%. Velocity increment >50% was found in 0/12 fetuses (0%) at 11-12 weeks, 5/20 (25%) at 13-14 weeks, and in 21/28 (75%) at 17-19 weeks. CONCLUSIONS: Blood velocity is higher in the umbilical vein at the abdominal wall than the cord, particularly after 13 weeks of gestation. If acceleration of blood velocity at the umbilical ring is a sign of a narrow inlet, it seems that a progressive tightening occurs during the second trimester.