The birth canal: correlation between the pubic arch angle,the interspinous diameter,and the obstetrical conjugate: a computed tomography biometric study in reproductive age women

Background: Assessment of pelvic configuration is an important factor in the prediction of a successful vaginal birth. However, manual evaluation of the pelvis is practically a vanishing art, and imaging techniques are not available as a real-time bed-side tool. Unlike the obstetrical conjugate diameter (OC) and inter spinous diameter (ISD), the pubic arch angle (PAA) can be easily measured by transperineal ultrasound.

Objectives: Three-dimensional computed tomography bone reconstructions were used to measure the three main birth canal diameters, evaluate the correlation between them, and establish the normal reference range for the inlet, mid-, and pelvic outlet.

Study design: Measurements of the PAA, obstetric conjugate (OC), and ISD were performed offline using three-dimensional post processing reconstruction in bone algorithm application of the pelvis on examinations performed for suspected renal colic in nonpregnant reproductive age woman. The mean of two measurements was used for statistical analysis which included reproducibility of measurements, regression curve estimation between PAA, OC, and ISD, and calculation of the respective reference range centiles for each PAA degree.

Results: Two hundred ninety-eight women comprised the study group. The mean?±?SD of the PAA, ISD, and OC were 104.9° (±7.4), 103.8?mm (±7.3), and 129.9?mm (±8.3), respectively. The intra- and interobserver agreement defined by the intraclass correlation coefficient (ICC) was excellent for all parameters (range 0.905–0.993). A significant positive correlation was found between PAA and ISD and between PAA and OCD (Pearson’s correlation?=?0.373 (p?p?=?.022), respectively). The best regression formula was found with quadratic regression for inter spinous diameter (ISD): 34.122778?+?(0.962182*PAA???0.002830*PAA²), and linear regression for obstetric conjugate (OC): 110.638397?+?0.183156*PAA. Modeled mean, SD, and reference centiles of the ISD and OCD were calculated using the above regression models as function of the PAA.

Conclusions: We report significant correlation between the three pelvic landmarks with greatest impact on the prediction of a successful vaginal delivery: the PAA which is easily measured sonographically and the ISD and OC which are not measurable by ultrasound. This correlation may serve as a basis for future studies to assess its utility and prognostic value for a safe vaginal delivery.     

Phenotypic manifestations of copy number variation in chromosome 16p13.11

The widespread clinical utilization of array comparative genome hybridization, has led to the unraveling of many new copy number variations (CNVs). Although some of these CNVs are clearly pathogenic, the phenotypic consequences of others, such as those in 16p13.11 remain unclear. Whereas deletions of 16p13.11 have been associated with multiple congenital anomalies, the relevance of duplications of the region is still being debated. We report detailed clinical and molecular characterization of 10 patients with duplication and 4 patients with deletion of 16p13.11. We found that patients with duplication of the region have varied clinical features including behavioral abnormalities, cognitive impairment, congenital heart defects and skeletal manifestations, such as hypermobility, craniosynostosis and polydactyly. These features were incompletely penetrant. Patients with deletion of the region presented with microcephaly, developmental delay and behavioral abnormalities as previously described. The CNVs were of varying sizes and were likely mediated by non-allelic homologous recombination between low copy repeats. Our findings expand the repertoire of clinical features observed in patients with CNV in 16p13.11 and strengthen the hypothesis that this is a dosage sensitive region with clinical relevance.     

Mosaic marker chromosome 16 resulting in 16q11.2-q12.1 gain in a child with intellectual disability, microcephaly, and cerebellar cortical dysplasia

Proximal duplications of the long arm of chromosome 16 are rare and only a few patients have been reported. Clinically, the patients do not have a distinctive syndromic appearance; however they all show some degree of intellectual disability and most have severely delayed speech development. We report on a child presenting with mild-to-moderate intellectual disability, microcephaly, language dyspraxia, and mild dysmorphisms who was found to have a mosaic gain of chromosome 16q (16q11.2-16q12.1). Magnetic resonance imaging done at the age of 4 years demonstrated cerebellar cortical dysplasia involving the vermis and hemispheres. This is the first report of cerebellar anomalies in a patient with partial trisomy 16q. The genes ZNF423 and CBLN1 found in the duplicated region play a role in the development of the cerebellum and may be responsible for the cerebellar cortical dysplasia.     

A hyperpolarized choline molecular probe for monitoring acetylcholine synthesis

Choline as a reporter molecule has been investigated by in vivo magnetic resonance for almost three decades. Accumulation of choline metabolites (mainly the phosphorylated forms) had been observed in malignancy in preclinical models, ex‐vivo, in vivo and in patients. The combined choline metabolite signal appears in ¹H‐MRS of the brain and its relative intensity had been used as a diagnostic factor in various conditions. The advent of spin hyperpolarization methods for in vivo use has raised interest in the ability to follow the physiological metabolism of choline into acetylcholine in the brain. Here we present a stable‐isotope labeled choline analog, [1,1,2,2‐D₄,2‐¹³C]choline chloride, that is suitable for this purpose. In this analog, the ¹³C position showed 24% polarization in the liquid state, following DNP hyperpolarization. This nucleus also showed a long T₁ (35 s) at 11.8 T and 25 °C, which is a prerequisite for hyperpolarized studies. The chemical shift of this ¹³C position differentiates choline and acetylcholine from each other and from the other water‐soluble choline metabolites, namely phosphocholine and betaine. Enzymatic studies using an acetyltransferase enzyme showed the synthesis of the deuterated‐acetylcholine form at thermal equilibrium conditions and in a hyperpolarized state. Analysis using a comprehensive model showed that the T₁ of the formed hyperpolarized [1,1,2,2‐D₄,2‐¹³C]acetylcholine was 34 s at 14.1 T and 37 °C. We conclude that [1,1,2,2‐D₄,2‐¹³C]choline chloride is a promising new molecular probe for hyperpolarized metabolic studies and discuss the factors related to its possible use in vivo. Copyright © 2010 John Wiley & Sons, Ltd.     

Selective mutism and abnormal electroencephalography (EEG) tracings

Epileptic discharges are not considered a part of the clinical picture of selective mutism, and electroencephalography is generally not recommended in its work-up. This report describes 6 children with selective mutism who were found to have a history of epilepsy and abnormal interictal or subclinical electroencephalography recordings. Two of them had benign epilepsy of childhood with centro-temporal spikes. The mutism was not related in time to the presence of active seizures. While seizures could be controlled in all children by medications, the mutism resolved only in 1. Although the discharges could be coincidental, they might represent a co-morbidity of selective mutism or even play a role in its pathogenesis. Selective mutism should be listed among the psychiatric disorders that may be associated with electroencephalographic abnormalities. It can probably be regarded as a symptom of a more complicated organic brain disorder.     

Discordance in the effects of Yersinia pestis on the dendritic cell functions manifested by induction of maturation and paralysis of migration

The encounter between invading microorganisms and dendritic cells (DC) triggers a series of events which include uptake and degradation of the microorganism, induction of a maturation process, and enhancement of DC migration to the draining lymph nodes. Various pathogens have developed strategies to counteract these events as a measure to evade the host defense. In the present study we found that interaction of the Yersinia pestis EV76 strain with DC has no effect on cell viability and is characterized by compliance with effective maturation, which is manifested by surface display of major histocompatibility complex class II, of costimulatory markers, and of the chemokine receptor CCR7. This is in contrast to maturation inhibition and cell death induction exerted by the related species Yersinia enterocolitica WA O:8. Y. pestis interactions with DC were found, however, to impair functions related to cytoskeleton rearrangement. DC pulsed with Y. pestis failed to adhere to solid surfaces and to migrate toward the chemokine CCL19 in an in vitro transmembrane assay. Both effects were dependent on the presence of the pCD1 virulence plasmid and on a bacterial growth shift to 37 degrees C prior to infection. Moreover, while instillation of a pCD1-cured Y. pestis strain into mouse airways triggered effective transport of alveolar DC to the mediastinal lymph node, instillation of Y. pestis harboring the plasmid failed to do so. Taken together, these results suggest that virulence plasmid-dependent impairment of DC migration is the major mechanism utilized by Y. pestis to subvert DC function.     

Interaction of Yersinia pestis with macrophages: limitations in YopJ-dependent apoptosis

The enteropathogenic Yersinia strains are known to downregulate signaling pathways in macrophages by effectors of the type III secretion system, in which YopJ/YopP plays a crucial role. The adverse effects of Yersinia pestis, the causative agent of plague, were examined by infecting J774A.1 cells, RAW264.7 cells, and primary murine macrophages with the EV76 strain and with the fully virulent Kimberley53 strain. Y. pestis exerts YopJ-dependent suppression of tumor necrosis factor alpha secretion and phosphorylation of mitogen-activated protein kinases and thus resembles enteropathogenic Yersinia. However, Y. pestis is less able to activate caspases, to suppress NF-kappaB activation, and to induce apoptosis in macrophages than the high-virulence Y. enterocolitica WA O:8 strain. These differences appear to be related to lower efficiency of YopJ effector translocation by Y. pestis. The efficiencies of effector translocation and of apoptosis induction can be enhanced either by using a high bacterial load in a synchronized infection or by overexpressing exogenous YopJ in Y. pestis. Replacing YopJ with the homologous Y. enterocolitica effector YopP can further enhance these effects. Overexpression of YopP in a yopJ-deleted Y. pestis background leads to rapid and effective translocation into target cells, providing Y. pestis with the high cytotoxic potential of Y. enterocolitica WA O:8. We suggest that the relative inferiority of Y. pestis in triggering cell death in macrophages may be advantageous for its in vivo propagation in the early stages of infection.