Soluble and Membranous Vascular Endothelial Growth Factor Receptor-2 in Pregnancies Complicated by Pre-Eclampsia

Purpose

There is a paucity of information on the serum soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) concentrations, membranous VEGFR-2 expression and the mechanism involved in their modulations during the clinical onset of pre-eclampsia. This cross-sectional study was conducted to evaluate the concentration of sVEGFR-2 in serum and to investigate the expression of membranous VEGFR-2 in placentae of pre-eclampsia group.

Materials and Methods

The serum levels of sVEGFR-2 (n = 120) and the expression of membranous VEGFR-2 in placentae (n = 100) were analysed at third trimester of pregnancy by enzyme linked immunosorbent assay (ELISA) and immunohistochemistry respectively. The diagnostic parameters of sensitivity, specificity and association of soluble and membranous VEGFR-2 in these patients were evaluated.

Results

The serum levels of sVEGFR-2 in pre-eclampsia patients were found to be significantly reduced (p = 0.01, p = 0.001) in early and late pre-eclamptic sub-groups as compared to their respective third trimester control sub-groups. Also, the receiver operating characteristic (ROC) curve analysis showed a cut-off value of 7350.4 pg/mL, higher sensitivity (76%) and specificity (76%) for sVEGFR-2 in late onset (> 34 weeks) pre-eclamptic group. Significant down-regulation of membranous VEGFR-2 immunoreactivity was observed in all the placental cells (p = 0.0001) at > 34 weeks preeclamptic group.

Conclusion

The reduced serum levels of soluble VEGFR-2 and the down-regulated expression of membranous VEGFR-2 in the study group denoted abnormality in VEGF mediated placental function in all placental cells and thus VEGFR-2 may be a key factor, intimately associated with pre-eclampsia. This study shows the clinical utility of soluble and membranous VEGFR-2 in pre-eclampsia patients.     

A population‐specific symmetric phase model to automatically analyze susceptibility‐weighted imaging (SWI) phase shifts and phase symmetry in the human brain

Purpose:

To create a population‐specific symmetric phase model and to evaluate the susceptibility‐weighted imaging (SWI) phase in terms of phase shift using different segmentation methods (manual and automatic) and phase shift symmetry, which is expected as a marker for lateralized Parkinson's disease (PD) symptoms.

Materials and Methods:

SWI and T₁‐weighted data from 25 PD patients and five healthy controls were acquired on a 3T MRI system. A population‐specific, symmetric phase model was developed. Regions of interest (ROIs) were defined manually on the phase model, manually on each individual data set, and automatically using model‐based segmentation (MBS). Manually‐ and MBS‐defined ROIs were compared using kappa values, and left‐right phase symmetry was evaluated using correlation analysis.

Results:

Independent of the analysis method, a phase increase from the anterior to the posterior putamen, and the average phase value relationship substantia nigra > globus pallidus > red nucleus was found. Phase symmetry analysis shows a difference between lateralized and symmetric PD.

Conclusion:

The symmetric phase model helps to analyze phase data with similar accuracy, but a greatly reduced tracing effort compared to individual tracing and also allows evaluating left‐right phase symmetries. J. Magn. Reson. Imaging 2010;31:215–220. © 2009 Wiley‐Liss, Inc.     

Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration

Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria‐infected erythrocytes and facilitates a highly specific binding to the placenta. ofCS is absent in other non‐malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines. We therefore explored whether ofCS in BL could act as anchor site for VAR2CSA‐expressing infected erythrocytes. In contrast to the placenta, we found no evidence of in vivo sequestering of infected erythrocytes in the BL tissue. Furthermore, we found VAR2CSA‐specific antibody titers in children with endemic BL to be lower than in control children from the same malaria endemic region. The abundant presence of ofCS in BL tissue and the absence of ofCS in non‐malignant tissue encouraged us to examine whether recombinant VAR2CSA could be used to target BL. We confirmed the binding of VAR2CSA to BL‐derived cells and showed that a VAR2CSA drug conjugate efficiently killed the BL‐derived cell lines in vitro. These results identify ofCS as a novel therapeutic BL target and highlight how VAR2CSA could be used as a tool for the discovery of novel approaches for directing BL therapy.     

Occupational exposure to solvents and bladder cancer: A population‐based case control study in Nordic countries

The objective of the study was to assess the relationship between exposure to selected solvents and the risk of bladder cancer. This study is based on the Nordic Occupational Cancer (NOCCA) database and comprises 113,343 cases of bladder cancer diagnosed in Finland, Iceland, Norway and Sweden between 1961 and 2005 and 566,715 population controls matched according to country, sex and birth year. Census‐based occupational titles of the cases and controls were linked with the job exposure matrix created by the NOCCA project to estimate quantitative cumulative occupational exposures. A conditional logistic regression model was used to estimate hazard ratios (HRs) and their 95% confidence intervals (95% CI). Increased risks were observed for trichloroethylene (HR 1.23, 95% CI 1.12–1.40), toluene (HR 1.20, 95% CI 1.00–1.38), benzene (HR 1.16, 95% CI 1.04–1.31), aromatic hydrocarbon solvents (HR 1.10, 95% CI 0.94–1.30) and aliphatic and alicyclic hydrocarbon solvents (HR 1.08, 95% CI 1.00–1.23) at high exposure level versus no exposure. The highest excess for perchloroethylene was observed at medium exposure level (HR 1.12, 95% CI 1.02–1.23). The study provides evidence of an association of occupational exposure to trichloroethylene, perchloroethylene, aromatic hydrocarbon solvents, benzene and toluene and the risk of bladder cancer.     

Accelerated hypofractionated adjuvant whole breast radiation with simultaneous integrated boost using volumetric modulated arc therapy for early breast cancer: A phase I/II dosimetric and clinical feasibility study from a tertiary cancer care centre of India

Background

Hypofractionation has become standard of care after Breast Conserving Therapy (BCT) in many European and few others western countries. Though still debatable, tumor cavity boost is routinely practised in our centre. Hypofractionation is not yet the current standard of practice in Asian countries. Employing hypofractionation and simultaneous integrated boost to lumpectomy cavity with conformal technique is not the current practice in this region. Hence the study was performed to see whether accelerated hypofractionation and simultaneous boost can be combined using volumetric modulated arc therapy (VMAT) in treating early breast cancer (EBC) patients.

Recurrent urinary tract infections in children: Preventive interventions other than prophylactic antibiotics

Urinary tract infection (UTI) is one of the most common childhood infections. Permanent renal cortical scarring may occur in affected children, especially with recurrent UTIs, leading to long-term complications such as hypertension and chronic renal failure. To prevent such damage, several interventions to prevent UTI recurrences have been tried. The most established and accepted prevention at present is low dose long-term antibiotic prophylaxis. However it has a risk of break through infections, adverse drug reactions and also the risk of developing antibiotic resistance. The search is therefore on-going to find a safer, effective and acceptable alternative. A recent meta-analysis did not support routine circumcision for normal boys with no risk factors. Vaccinium Macrocarpon (cranberry), commonly used against UTI in adult women, is also effective in reducing the number of recurrences and related antimicrobial use in children. Sodium pentosanpolysulfate, which prevents bacterial adherence to the uroepithelial cells in animal models, has shown conflicting results in human trials. When combined with antibiotic, Lactobacillus acidophilus (LA-5) and Bifidobacterium, by blocking the in vitro attachment of uropathogenic bacteria to uroepithelial cells, significantly reduce in the incidence of febrile UTIs. Deliberate colonization of the human urinary tract of patients with recurrent UTI with Escherichia-coli (E. coli) 83972 has resulted in subjective benefit and less UTI requiring treatment. The non-pathogenic E. coli isolate NU14 DeltawaaL is a candidate to develop live-attenuated vaccine for the treatment and prevention of acute and recurrent UTI. Diagnosing and treating dysfunctional elimination syndromes decrease the incidence of recurrent UTI. A meta-analysis found the lack of robust prospective randomized controlled trials limited the strength of the established guidelines for surgical management of vesicoureteral reflux. In conclusion, several interventions, other than antibiotic prophylaxis, for the prevention of recurrent UTI have been tried and, although showing some promise, they do not provide so far a definitive effective answer. Finding suitable alternatives still requires further high quality research of those seemingly promising interventions.     

Orbital tuberculosis: Clinicopathological correlation and diagnosis using PCR in formalin-fixed tissues

This article describes the clinicopathological correlation and challenges encountered in the diagnosis of orbital tuberculosis (TB). Retrospective, interventional case series. A chart review of six patients who underwent biopsy for an orbital mass between January 2012 and December 2013 was performed. Institutional review board approval was obtained for the study. Clinical, radiological, and laboratory findings were documented, and response to antitubercular therapy (ATT) was noted. Age at presentation ranged from 18 to 64 years and duration of complaints varied from 2 weeks to 2 months. Pain, redness, and swelling with an orbital mass on computerized tomography (CT) were the common features. None of the patients was clinically suspected to have orbital TB at presentation. History of prior contact with a patient of TB and history of prior TB were present in one case each. Chest radiography (CXR) showed pulmonary consolidation in one case. Tuberculin skin test (TST) readings ranged from nonreactive to 23 mm. The presence of sputum acid fast bacilli (AFB) was tested in three cases and was negative. Polymerase chain reaction (PCR) for MPB64 gene was positive in all six cases. All cases responded to ATT. Clinical presentation of orbital TB can be variable and can simulate conditions like inflammatory disease and malignancy. Biopsy with histopathology plays a key role in diagnosis. Supportive laboratory investigations are necessary to clinch the diagnosis in cases where histopathology is suggestive of TB. In this regard, PCR for Mycobacterium tuberculosis (MTB) on tissue biopsy specimens may be a sensitive diagnostic tool.     

First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy

We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies (infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6 (IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody (tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may lead to aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling.     

Fat oxidation before and after a high fat load in the obese insulin-resistant state

BACKGROUND: Obesity may be associated with a lowered use of fat as a fuel, which may contribute to the enlarged adipose tissue stores. AIM: The aim of the present study was to study fatty acid use in the fasting state and in response to a high fat load in a large cohort of obese subjects (n = 701) and a lean reference group (n = 113). METHODS: Subjects from eight European centers underwent a test meal challenge containing 95 en% fat [energy content 50% of estimated resting energy expenditure (EE)]. Fasting and postprandial fat oxidation and circulating metabolites and hormones were determined over a 3-h period. RESULTS: Postprandial fat oxidation (as percent of postprandial EE, adjusted for fat mass, age, gender, center, and energy content of the meal) decreased with increasing body mass index (BMI) category (P < 0.01), an effect present only in those obese subjects with a relatively low fasting fat oxidation (below median, interaction BMI category x fasting fat oxidation, P < 0.001). Fasting fat oxidation increased with increasing BMI category (P < 0.001), which was normalized after adjustment for fat-free mass and fat mass. Furthermore, insulin resistance was positively associated with postprandial fat oxidation (P < 0.05) and negatively associated with fasting fat oxidation (expressed as percent of EE), independent of body composition. CONCLUSIONS: The present data indicate an impaired capacity to regulate fat oxidation in the obese insulin-resistant state, which is hypothesized to play a role in the etiology of both obesity and insulin resistance.