Routine Screening for Rubella and CMV Antibodies During Pregnancy: Is it Justifiable?

Background

Rubella and cytomegalovirus (CMV) screening during pregnancy is routinely carried out in India. However, its value has been questioned due to the absence of clearly effective intervention.

Objectives

This retrospective study evaluates the usefulness of rubella and CMV antibody screening during pregnancy.

Materials and Methods

Serum samples received from pregnant women and children were tested for rubella- and CMV-specific IgM antibodies by capture ELISA. The data were analyzed to determine the incidence of rubella and CMV infection during pregnancy and in congenital infections.

Results

In asymptomatic pregnant females (n = 505), rubella positivity was 3.16 % and in women with bad obstetric history (BOH) (n = 220), it was 7.72 %, while CMV positivity was 5.9 % in both asymptomatic pregnant women and in women with BOH. In children (n = 200), the overall positivity for rubella- and CMV-specific IgM antibodies was 15 and 25 %, respectively. A declining trend was observed in the incidence of both rubella and CMV infections in pregnant women and in women with BOH. In children, the incidence of congenital rubella syndrome has declined, but the incidence of CMV infection has remained almost the same in 5 years.

Conclusion

The incidence of rubella has reduced over the past 5 years and can further be prevented by providing direct protection to women and school girls with rubella vaccines. Primary CMV infection in pregnancy is the main problem, and due to the unavailability of efficient and safe treatment, routine antenatal screening for rubella and CMV should be reserved for women with obstetric complications only.     

The contribution of epidermal growth factor receptor (EGFR) signaling pathway to radioresistance in human gliomas: a review of preclinical and correlative clinical data

PURPOSE: The epidermal growth factor receptor (EGFR) pathway is frequently upregulated in high-grade gliomas via gene amplification and by specific mutations that render EGFR constitutively active (EGFRvIII). METHODS AND MATERIALS: This review highlights EGFR's role in mediating radiation resistance in gliomas: underlying molecular mechanisms, with discussion of relevant preclinical and clinical correlative data. RESULTS: Preclinical and emerging clinical data suggest that EGFR signaling plays a potentially important role in mediating radiation resistance in human gliomas. CONCLUSIONS: Targeting EGFR alone, or in combination with its downstream mediators, represents a promising new approach for the management of glioma patients.     

A Robust Method for Ventriculomegaly Detection from Neonatal Brain Ultrasound Images

Ventriculomegaly is the most commonly detected abnormality in neonatal brain. It can be defined as a condition when the human brain ventricle system becomes dilated. This in turn increases the intracranial pressure inside the skull resulting in progressive enlargement of the head. Sometimes it may also cause mental disability or death. For these reasons early detection of ventriculomegaly has become an important task. In order to identify ventriculomegaly from neonatal brain ultrasound images, we propose an automated image processing based approach that measures the anterior horn width as the distance between medial wall and floor of the lateral ventricle at the widest point. Measurement is done in the plane of the scan at the level of the intraventricular foramina. Our study is based on neonatal brain ultrasound images in the midline coronal view. In addition to ventriculomegaly detection, this work also includes both cross sectional and longitudinal study of anterior horn width of lateral ventricles. Experiments were carried out on brain ultrasound images of 96 neonates with gestational age ranging from 26 to 39 weeks and results have been verified with the ground truth provided by doctors. Accuracy of the proposed scheme is quite promising.     

Prevalence of BER gene polymorphisms in sporadic breast cancer

Studies suggest that breast cancer is initiated by the induction of somatic mutations from errors in the base excision repair (BER) of endogenous estrogen-induced abasic sites. If so, the inheritance of certain polymorphic mutations in BER genes involved in the incorporation and management of such errors should increase the risk of breast cancer. To test this hypothesis, we examined breast tissues from 48 women (controls, histopathologically normal tissue from reduction mammoplasty) and 40 women with breast cancer (breast tumor-adjacent, histopathologically normal tissues) for the presence of reported polymorphic mutations in four BER genes. The breast tissues were obtained from the Cooperative Human Tissue Network-western division and from the University of Nebraska Medical Center. Using PCR-RFLP procedures, the XRCC1 gene was examined for Arg194Trp and Arg399Gln, APE1 for Asp148Glu, LIG3alpha for Arg780His and PARP1 for Pro377Ser mutations. The women in this study carried only the XRCC1 Arg399Gln polymorphism. This result was surprising because APE1 148Glu was reported to be frequently inherited (allele frequency, 0.47-0.495) by USA and European women. Thus, the USA women in our study are genetically different from those in the previous studies. Among the control women, 21 (43.75%) were Arg/Arg wild-types, 20 (41.67%) were Arg/Gln heterozygotes and 7 (14.6%) were Gln/Gln homozygotes. Among the breast cancer cases, 11 (27.5%) were Arg/Arg wild-types, 16 (40%) were Arg/Gln heterozygotes and 13 (32.5%) were Gln/Gln homozygotes. Thus, the Gln allele was significantly more frequent in breast cancer cases (allele frequency, 0.52) than in controls (allele frequency, 0.35), suggesting that XRCC1 399Gln may enhance the risk of breast cancer.     

Allele-specific expression in the germline of patients with familial pancreatic cancer: an unbiased approach to cancer gene discovery

Physiologic allele-specific expression (ASE) in germline tissues occurs during random X-chromosome inactivation and in genomic imprinting, wherein the two alleles of a gene in a heterozygous individual are not expressed equally. Recent studies have confirmed the existence of ASE in apparently non-imprinted autosomal genes; however, the extent of ASE in the human genome is unknown. We explored ASE in lymphoblastoid cell lines of 145 individuals using an oligonucleotide array based assay. ASE of autosomal genes was found to be a very common phenomenon in approximately 20% of heterozygotes at 78% of SNPs at 84% of the genes examined. Comparison of 100 affected individuals from familial pancreatic cancer kindreds and 45 controls revealed three types of changes in the germline: (a) loss of ASE, (b) gain of ASE, and, (c) rare instances of "extreme" (near monoallelic) ASE. The latter changes identified heterozygous deleterious mutations in a subset of these genes. Consequently, an ASE assay efficiently identifies candidate disease genes with altered germline expression properties as compared to controls, and provides insights into mechanisms that confer an inherited disease risk for pancreatic cancer.     

The added value of concurrently administered temozolomide versus adjuvant temozolomide alone in newly diagnosed glioblastoma

Purpose Temozolomide (TMZ), given concurrently with radiotherapy (RT) and as adjuvant monotherapy afterwards, has led to improved survival in glioblastoma multiforme (GBM). However, it is unclear whether its primary mechanism of action is through enhancement of radiation response, independent cytotoxicity, or both. We sought to determine the relative contribution of concomitant temozolomide in patients treated by concurrent and adjuvant TMZ versus adjuvant TMZ alone in the setting of newly diagnosed GBM. Methods and Materials We identified patients diagnosed with GBM and treated with surgery, involved-field radiotherapy, and chemotherapy at MGH between 2002 and 2004. Eligible patients received either adjuvant temozolomide alone (group 1) or temozolomide concurrently with RT followed by adjuvant TMZ (group 2). The primary endpoint of this retrospective analysis was overall survival (OS). Results Forty-three patients (group 1, n = 21; group 2, n = 22) were included in this study. The median follow-up was 33.7 months for surviving patients. There were no significant differences in baseline characteristics between these two groups. On univariate analysis, patients who received concurrent and adjuvant temozolomide experienced a 2-year OS of 51% and median survival of 25.5 months, compared with a 2-year OS of 36% and median survival of 15.6 months for group 1 patients (P < 0.05). On multivariable analysis, the hazard ratio (HR) favoring concurrent TMZ trended towards significance (HR = 0.51, P = 0.08) despite modest patient numbers. Conclusions Concurrent and adjuvant TMZ was associated with improved survival compared to adjuvant TMZ alone, highlighting the potentiation of radiation effect by temozolomide in the clinical setting. Statement of originality: This work is completely original and has not been published or presented elsewhere. John W. Henson and Bindu Avutu contributed equally to this publication.