Julian Crasta

Catastrophic antiphospholipid antibody syndrome.

Antiphospholipid antibody syndrome (APS) is characterized by recurrent thrombosis with the presence of circulating antiphospholipid antibodies. A diagnosis of APS requires the presence of at least one clinical and one laboratory criteria (detection of aCL IgG or IgM antibodies or the presence of lupus anticoagulant on two or more consecutive occasions 6xa0weeks apart). A severe, rapidly progressive form characterized by clinical involvement of at least three different organ systems with histopathological evidence of small and large vessel occlusion is termed catastrophic antiphospholipid syndrome. Early recognition of APS is crucial since aggressive management can result in a favorable outcome. We present the case of a 12-year-old boy who presented with a devastating illness with multiple thrombotic episodes and rapidly progressive renal failure.

Significance of preoperative thrombocytosis in epithelial ovarian cancer.

BACKGROUNDnReactive thrombocytosis is reported in a variety of solid tumors. A few studies have documented preoperative thrombocytosis in ovarian cancer and identified it as a marker of aggressive tumor biology.nnnAIMnTo study the incidence of preoperative thrombocytosis (platelets greater than 400x10) in epithelial ovarian cancer and its association with other clinicopathologic factors.nnnMATERIALS AND METHODSnSixty-five patients with invasive ovarian epithelial cancer were retrospectively reviewed and analyzed for the association preoperative thrombocytosis with other clinical and histopathological prognostic factors. Means were analyzed by Students t test; proportions were determined by Chi-square analysis.nnnRESULTSnTwenty of 65 (37.5%) patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis were found to have lower hemoglobin (P < 0.0002), more advanced stage disease (P < 0.05) and higher grade tumors (P < 0.02). Patients with thrombocytosis had greater likelihood of subpotimal cytoreduction.nnnCONCLUSIONSnPreoperative thrombocytosis is a frequent finding in ovarian carcinomas and their association with advanced stage disease and higher grade denotes that platelets play a role in the tumor growth and progression.

An unusual case of primary osteosarcoma of the rib in an adult

Primary osteosarcomas are one of the most common malignant bone tumors principally affecting the long bones in children and adolescents. An unusual case of a primary osteoblastic osteosarcoma of the rib in a 42-year-old male is presented here. The patient underwent a wide excision of the tumor and chest wall reconstruction. Although clinically unsuspected in this unusual site, the classic microscopic feature of a ramifying osteoid matrix amidst the tumor cells was diagnostic of an osteosarcoma.

Placental expression of the insulin receptor binding protein GRB10: Relation to human fetoplacental growth and fetal gender

INTRODUCTIONnImprinted genes play an important role in mammalian fetoplacental growth and development. We have evaluated whether the placental expression of two imprinted genes, growth factor receptor-binding protein 10 (GRB10) and pleckstrin homology-like domain, family A, member 2 (PHLDA2) correlate with human fetoplacental growth parameters.nnnMETHODSnPlacentae (n = 77) were collected from small- (SGA) and appropriate- (AGA) for gestational age full-term singleton pregnancies (n = 36 SGA and 41 AGA). Placentae and neonates were weighed at birth. Realtime quantitative PCR was performed to assess placental transcript abundance of GRB10 and PHLDA2 normalized to a panel of reference genes.nnnRESULTSnPlacental GRB10 transcript abundance associated positively with placental weight (r = 0.307, P = 0.007), birth weight (r = 0.267, P = 0.019) and neonatal head circumference (r = 0.280, P = 0.014). Placental GRB10 transcript levels were significantly lower in male SGA placentae compared to the male AGA placentae. Placental PHLDA2 transcript abundance did not show any associations with maternal, placental or neonatal parameters.nnnDISCUSSIONnPlacental GRB10 expression was found to be associated positively with placental weight, birth weight, and neonatal head circumference, especially in males. Hence, we speculate that placental GRB10 plays a role in regulating fetoplacental growth and thereby in the pathophysiology of fetal growth restriction in the context of fetal gender.

Ovarian serous carcinoma: relationship of p53 and bcl-2 with tumor angiogenesis and VEGF expression.

The aim of the study was to assess the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in ovarian serous carcinoma and to examine their relation with apoptosis.Paraffin-embedded specimens of 41 cases of ovarian serous carcinomas were evaluated by immunohistochemistry for VEGF, p53, and bcl-2 expression. MVD was assessed with CD31 staining. We investigated the association of tumor angiogenesis (MVD and VEGF) with clinicopathologic factors, p53 overexpression, and bcl-2 expression.There was a significant correlation between high MVD and suboptimal debulking and advanced stage disease. A significant negative correlation was expressed between bcl-2 and VEGF expression. In univariate analysis, only stage had a significant impact on disease-free survival.The results of this study suggest that higher degree of angiogenesis is associated with suboptimal debulking and advanced-stage disease. Expression of VEGF had negative association with VEGF expression.

Pediatric malakoplakia of colon: a report of two cases

Gastrointestinal system is the second most common site for the occurrence of malakoplakia. We report two cases of pediatric colonic malakoplakia with the endoscopic and characteristic histologic findings. Malakoplakia is rare in pediatric age group, no clinical and endoscopic findings are diagnostic and the condition can masquerade as other conditions like inflammatory bowel disease and tumors.

How accurate is intraoperative frozen section in the diagnosis of ovarian tumors

The aim of this study was to evaluate the accuracy of intraoperative frozen section of ovarian tumors and to analyze the factors that influence the accuracy.

An audit of cervicovaginal cytology in a teaching hospital: Are atypical glandular cells under-recognised on cytological screening?

Background: Cervical cytology screening for carcinoma of the cervix in India is mainly opportunistic in nature and is practiced mainly in urban centres. The effectiveness of cervical cytology screening depends on various factors. The quality of cervicovaginal cytology service is assessed by various quality indices and by cyto-histology correlation, which is the most important quality assurance measure. Aims: To describe the cervical cytology diagnoses, estimate the quality indices, and evaluate the discrepant cases on cytohistological correlation. Settings and Design: Retrospective observational study from a tertiary care centre in South India. Materials and Methods: Using a database search, all the cervicovaginal cytology reported during the period of 2002-2006 was retrieved and various diagnoses were described. The data was analysed to assess the quality indices. The cytohistologically discrepant cases were reviewed. Results: A total of 10,787 cases were retrieved, of which 98.14% were labeled negative and 1.36% were unsatisfactory for evaluation. A few (0.81%) of the cases were labeled as squamous intraepithelial lesions and 0.38% as atypical squamous cells. The ASCUS: SIL ratio was 0.5. Cytohistological correlation revealed a total of ten cases with significant discrepancy. The majority of these were carcinomas that were misdiagnosed as atypical glandular cells. These cytology smears and the subsequent biopsies were reviewed to elucidate the reasons for the discrepancies. Conclusions: The cervical cytology service at our centre is well within the accepted standards. An increased awareness of cytological features, especially of glandular lesions, a good clinician-laboratory communication and a regular cytohistological review would further improve the diagnostic standards.

Combined Vitamin B-12 and Balanced Protein-Energy Supplementation Affect Homocysteine Remethylation in the Methionine Cycle in Pregnant South Indian Women of Low Vitamin B-12 Status.

Background: Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy and may affect epigenetic modifications of the fetal genome.Objective: The objective of this randomized, partially open-labeled intervention trial was to examine the effect of supplemental high-quality protein and vitamin B-12 on third-trimester methionine kinetics in pregnant Indian women with a low vitamin B-12 status.Methods: Pregnant women with low serum vitamin B-12 concentrations (<200 pmol/L) were randomly assigned to 1 of 3 groups: the first group received balanced protein-energy supplementation of 500 mL milk/d plus a 10-μg vitamin B-12 tablet/d (M+B-12 group; n = 30), the second group received milk (500 mL/d) plus a placebo tablet (M+P group; n = 30), and the third group received a placebo tablet alone (P group; n = 33). Third-trimester fasting plasma amino acid kinetics were measured by infusing 1-13C,methyl-2H3-methionine, ring-2H5-phenylalanine, ring-2H4-tyrosine,1-13C-glycine, and 2,3,3-2H3,15N-serine in a subset of participants. Placental mRNA expression of genes involved in methionine pathways, placental long interspersed nuclear elements 1 (LINE-1) methylation, and promoter methylation levels of vascular endothelial growth factor (VEGF) were analyzed.Results: Remethylation rates in the M+B-12, M+P, and P groups were 5.1 ± 1.7, 4.1 ± 1.0, and, 5.0 ± 1.4 μmol ⋅ kg-1 ⋅ h-1, respectively (P = 0.057), such that the percentage of transmethylation remethylated to methionine tended to be higher in the M+B-12 group (49.5% ± 10.5%) than in the M+P group (42.3% ± 8.4%; P = 0.053) but neither differed from the P group (44.2% ± 8.1%; P > 0.1). Placental mRNA expression, LINE-1, and VEGF promoter methylation did not differ between groups.Conclusions: Combined vitamin B-12 and balanced protein-energy supplementation increased the homocysteine remethylation rate in late pregnancy. Thus, vitamin B-12 along with balanced protein-energy supplementation is critical for optimal functioning of the methionine cycle in the third trimester of pregnancy in Indian women with low serum vitamin B-12 in early pregnancy. This trial was registered at clinicaltrials.gov as CTRI/2016/01/006578.

Placental expression of DNA methyltransferase 1 (DNMT1): Gender-specific relation with human placental growth

AIMSnPlacental physiology and morphology is critically regulated by DNA methylation. As such, placental global DNA methylation and transcript abundance of placental DNA methyltransferases (DNMT1 and DNMT3A) may relate to placental and fetal growth in human pregnancies. We aimed to test correlations of human fetoplacental parameters and birth weight with the placental expression of DNA methyltransferases (DNMT1 and DNMT3A) and placental global methylation.nnnSUBJECTS AND METHODSnPlacentae (nxa0=xa0109) were collected from small- (SGA) and appropriate- (AGA) for gestational age full-term singleton pregnancies (nxa0=xa056 SGA and 53 AGA). Placentae and neonates were weighed at birth. Realtime quantitative PCR was performed to assess placental transcript abundance of DNMT1, DNMT3A and DNTMT3B normalized to a panel of reference genes. LINE-1 methylation was measured using a quantitative MethyLight assay in a subset of samples (nxa0=xa068). Associations of placental transcript abundances of DNMT1, DNMT3A and DNMT3B and of LINE-1 methylation levels with maternal, placental and neonatal parameters were tested.nnnRESULTSnPlacental DNMT1 transcript abundance associated positively with placental weight (βxa0=xa010.21, Pxa0=xa00.013). This association was specific to the AGA births (βxa0=xa012.77, Pxa0=xa00.022) and was absent in the SGA births. Association of DNMT1 expression with placental weight and birth weight within the AGA births was specific to the female gender (Birth weight: βxa0=xa083.61, Pxa0=xa00.043; Placental weight: βxa0=xa023.92, Pxa0=xa00.025). Placental DNMT1 transcript levels were not different according to SGA status or gender. Placental DNMT3A transcript levels and LINE-1 methylation levels did not show any associations with maternal, placental and neonatal parameters.nnnCONCLUSIONSnPlacental DNMT1 expression was found to be associated positively with placental weight and birth weight, specifically in the female AGA births. Thus, we hypothesize that placental DNMT1 participates in fetoplacental growth in a fetal gender-specific manner.