Appraising the factors favouring uranium mobilization and associated health risk assessment in groundwaters of north-western India.

An attempt has been made in this study to evaluate the factors favoring the uranium mobilization into the groundwater of Northwest India using uranium isotope activity ratio (234U/238U), radon (222Rn) and environmental isotopes of water (2H, 18O and 3H). The values range from 23 - 597 µg/L for total uranium and 634-3210 Bq/m3 for radon and the corresponding annual effective dose is estimated to be 18.9-490 µSv/a and 6.2-31.5 µSv/a respectively. Uranium activity ratio (UAR) varies from 0.68 - 1.17 and maximum samples indicate secular equilibrium. Environmental isotopic data indicates that the source to groundwater is vertical percolation of rainwater in the case of shallow zone while regional flows from outcrop areas recharge the deep groundwater. A wide scatter is noticed in environmental 3H content (0.23-6.62 TU) indicating both fast and sluggish water flows. The UAR phase diagram suggests that leaching process controls the uranium mobilization into the groundwater. The correlations among UAR, uranium and Uexcess further indicate oxidative nature of leaching process. Statistical treatment of the obtained data along with available geochemical and isotope evidences suggest that source of uranium is common but the driving processes are different for shallow and deep zone. Influences of root zone CO2, oxic species from irrigation return flows and water level fluctuations are also evaluated. Low uranium, low UAR, low 3H and high 222Rn activity in deep zone suggest uranium being released from the roll front as well as transported from outcrop regions. This study highlights the application of uranium isotope ratio, radon and environmental isotopes in assessing vulnerability of alluvial aquifers towards uranium contamination.

Distribution of environmental tritium in rivers, groundwater, mine water and precipitation in Goa, India.

Tritium concentration in rivers, groundwater, precipitation and mine pits water, all over Goa state was characterized to find out spatial and temporal variability of tritium. Twenty four water samples were collected during pre-monsoon and post-monsoon and analyzed for their tritium concentration. The mean tritium concentration in surface and sub-surface hydrosphere is 2.5 (±0.6) TU. The mean concentration of tritium in rivers, groundwater, mines pits water and rain water are 2.9 (±0.5) TU, 1.95 (±0.5) TU, 2.5(±0.3) TU and 3.1(±0.1) TU respectively. The tritium distribution in all the samples shows modern precipitation (post-1950) component in surface and sub-surface hydrosphere of Goa. The HYSPLIT4.0 air mass trajectory model and atmospheric circulation pattern suggest that the moisture origin was from the Arabian Sea and this low tritium moisture is diluting the tritium concentration of surface hydrosphere near the coastal area. The tritium concentration in surface hydrosphere shows more and more enrichment as one move inland (i.e. away from the coast). Significant seasonal change is observed in the surface hydrosphere. The pre-monsoon samples showed higher tritium concentration than post-monsoon samples. This may be due to high rate of re-evaporation of water and a reduction in the supply of oceanic moisture during the summer (pre-monsoon).

Isotope investigation on groundwater recharge and dynamics in shallow and deep alluvial aquifers of southwest Punjab.

Groundwater samples collected from the alluvial aquifers of southwest Punjab, both shallow and deep zones were measured for environmental tritium (3H) and stable isotopes (2H and 18O) to evaluate the source of recharge and aquifer dynamics. The shallow groundwater shows wide variation in isotopic signature (δ18O: -11.3 to -5.0‰) reflecting multiple sources of recharge. The average isotopic signature of shallow groundwaters (δ18O: -6.73 ± 1.03‰) is similar to that of local precipitation (-6.98 ± 1.66‰) indicating local precipitation contributes to a large extent compared to other sources. Other sources have isotopically distinct signatures due to either high altitude recharge (canal sources) or evaporative enrichment (irrigation return flow). Deep groundwater shows relatively depleted isotopic signature (δ18O: -8.6‰) and doesn't show any evaporation effect as compared to shallow zone indicating recharge from precipitation occurring at relatively higher altitudes. Environmental tritium indicates that both shallow (3H: 5 - 10 T.U.) and deeper zone (3H: 1.5 - 2.5 T.U.) groundwaters are modern. In general the inter-aquifer connections seem to be unlikely except a few places. Environmental isotope data suggests that shallow groundwater is dynamic, local and prone to changes in land use patterns while deep zone water is derived from distant sources, less dynamic and not impacted by surface manifestations. A conceptual groundwater flow diagram is presented.

Anatomy of left atrioventricular valve (mitral valve) leaflets in adult Indian cadavers / Anatomía de los velos valvulares en la valva atrioventricular izquierda (válvula mitral) en cadáveres indios adultos

The atrioventricular valve is the most commonly repaired valve of the heart. Interventional procedures like annuloplasties, valvotomy/valvuloplasty, repair/replacement of the valve for regurgitation or prolapse are increasing by the day. This necessitates a clear understanding of the mitral valve anatomy. The present study is an attempt to revisit the anatomy of mitral valve. The present study was conducted on 34 adult embalmed heart specimens. Based on the newly defined criteria, observations were made on: 1) Number of commissures and their positions, 2) Number and position of leaflets, 3) Number and position of minor commissures, 4) Annular circumference (AC), 5) Length of annular attachment of each leaflet (LAA), 6) Maximum width of coapted/ folded margin (FM) of the anterior and posterior leaflet, 7) The surface area of each leaflet (SA). The observations were analyzed statistically. The findings of the present study and the subsequent statistical analysis offer a dynamic concept of the anatomy of mitral valve leaflets. It suggests that the valvular anatomy depends upon a complex interplay of various valve components. The extra leaflets tend to occur when annular circumference increases and is not appropriately compensated by various valvular elements. The different methodology adopted in the present study and the interpretations deduced hereupon, shall dispel the existing ambiguities in the description of the leaflets and improve our understanding of the structure and function of the mitral valve complex.

La valva atrioventricular es la valva más comúnmente reparada del corazón. Los procedimientos intervencionistas como anuloplastías, valvotomía/valvoplastía, reparación/reemplazo de la valva por la regurgitación o prolapso están aumentando día a día. Para ello, se requiere una clara comprensión de la anatomía de la valva atrioventricular. El presente estudio intenta volver a examinar la anatomía de la valva atrioventricular. Se estudiaron 34 corazones de adultos embalsamados. Sobre la base de los criterios definidos, se realizaron las siguientes observaciones: 1) número de comisuras y sus posiciones, 2) número y localización de los velos, 3) número y localización de las comisuras menores, 4) circunferencia anular (AC), 5) longitud de la unión anular de cada valva (LAA), 6) ancho máximo del margen de coaptación/margen velar (FM) de los velos anterior y posterior y 7) área de superficie de cada valva (SA). Las observaciones fueron analizadas estadísticamente. Los resultados del presente estudio y el análisis estadístico ofrecen un concepto dinámico de la anatomía de la valva atrioventricular. Se sugiere que la anatomía de las valvas depende de una interacción compleja de varios de sus componentes. Los velos adicionales tienden a aparecer cuando aumenta la circunferencia anulares y no se compensa adecuadamente por diversos elementos valvares. La diferente metodología adoptada en el presente estudio sus interpretaciones, podrían disipar ambigüedades existentes en la descripción de las valvas y mejorar nuestra comprensión de la estructura y función del complejo de la valva atrioventricular.

A novel orthotopic mouse model of head and neck cancer and lymph node metastasis.

Prognosis of head and neck squamous cell carcinoma (HNSCC) is largely determined by the extent of lymph node (LN) metastasis at diagnosis, and this appears to be controlled by cancer cell genetics. To examine the role of these genes in LN metastasis, we created a human-in-mouse orthotopic model of HNSCC and performed comparative microarray analysis of gene expression between populations of HNSCC cell lines derived before and after serial transplantation and in vivo metastasis in mice. Microarray analysis comparing the USC-HN3-GFP, USC-HN3-GFP-G1 and USC-HN3-GFP-G2 cell lines identified overexpression of genes implicated in epithelial-to- mesenchymal transition and the formation of cancer stem cells, including CAV-1, TLR-4 (Toll-like receptor 4), MMP-7 (matrix metalloproteinase 7), ALDH1A3, OCT-4 and TRIM-29. Ingenuity Pathway Analysis confirmed upregulation of respective gene signaling pathways in the USC-HN1-GFP-G2 cell line. Patient HNSCC samples from advanced stages overexpressed ALDH1A3, CAV-1 and MMP-7. Our results show that CAV-1, TLR-4, MMP-7, ALDH1A3, OCT-4 and TRIM-29 have increased expression in HNSCC cells selected for an enhanced metastatic phenotype and suggest that these genes may have an important role in the metastatic potential of HNSCC cells. Inhibition of these genes may therefore have prognostic and therapeutic utility in HNSCC.

Transoral robotic resection of oropharyngeal synovial sarcoma in a pediatric patient.

Localized synovial cell sarcomas are treated with surgical resection followed by chemo-radiation. Surgical resection of synovial sarcoma of the oropharynx and hypopharynx involves lip-splitting mandibulotomy resulting in treatment related morbidity. We report the successful use of Trans Oral Robotic Surgery for resection of localized synovial sarcoma of the lateral pharyngeal wall in a 15 year old patient. We were able to achieve negative surgical margins and avoid open surgery with its associated morbidity. At 2 years follow-up, patient is disease free, with no deficits in speech or swallowing functions and no cosmetic deformity.

Predictive value of bedside clinical signs and symptoms in early diagnosis of deep vein thrombosis in acutely ill medical patients with special reference to deep vein thrombosis prophylaxis.

Deep vein thrombosis (DVT) is highly elusive in the sense, that being so common among acutely ill hospitalised patients with multiple risk factors yet remain mostly unrecognised particularly at the early stage. Pulmonary thrombo-embolism (PTE), the most sinister acute complication of DVT carries a high mortality on one hand and involves expensive medicare and investigations on the other hand. Many studies that have been undertaken in recent past on this important clinical issue have produced a wealth of published data to show that in the absence of prophylaxis for DVT in such a setting the mortality rates were significantly high. The need to exphasise importance of DVT prophylaxis has now become a unified word in the management of acutely ill medical patient. This article emphasises the advantages of astute bedside clinical examination in identifying DVT early and the need for prophylaxis to prevent this morose condition.

Selective, novel spleen tyrosine kinase (Syk) inhibitors suppress chronic lymphocytic leukemia B-cell activation and migration.

Syk is a protein tyrosine kinase that couples B-cell receptor (BCR) activation with downstream signaling pathways, affecting cell survival and proliferation. Moreover, Syk is involved in BCR-independent functions, such as B-cell migration and adhesion. In chronic lymphocytic leukemia (CLL), Syk becomes activated by external signals from the tissue microenvironment, and was targeted in a first clinical trial with R788 (fostamatinib), a relatively nonspecific Syk inhibitor. Here, we characterize the activity of two novel, highly selective Syk inhibitors, PRT318 and P505-15, in assays that model CLL interactions with the microenvironment. PRT318 and P505-15 effectively antagonize CLL cell survival after BCR triggering and in nurse-like cell-co-cultures. Moreover, they inhibit BCR-dependent secretion of the chemokines CCL3 and CCL4 by CLL cells, and leukemia cell migration toward the tissue homing chemokines CXCL12, CXCL13, and beneath stromal cells. PRT318 and P505-15 furthermore inhibit Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering. These findings demonstrate that the selective Syk inhibitors PRT318 and P505-15 are highly effective for inhibition of CLL survival and tissue homing circuits, and support the therapeutic development of these agents in patients with CLL, other B-cell malignancies and autoimmune disorders.

Recent advances in breast MRI and MRS.

Breast MRI is an area of intense research and is fast becoming an important tool for the diagnosis of breast cancer. This review covers recent advances in breast MRI, MRS, and image post-processing and analysis. Several studies have explored a multi-parametric approach to breast imaging that combines analysis of traditional contrast enhancement patterns and lesion architecture with novel methods such as diffusion, perfusion, and spectroscopy to increase the specificity of breast MRI studies. Diffusion-weighted MRI shows some potential for increasing the specificity of breast lesion diagnosis and is even more promise for monitoring early response to therapy. MRS also has great potential for increasing specificity and for therapeutic monitoring. A limited number of studies have evaluated perfusion imaging based on first-pass contrast bolus tracking, and these clearly identify that vascular indices have great potential to increase specificity. The review also covers the relatively new acquisition technique of MR elastography for breast lesion characterization. A brief survey of image processing algorithms tailored for breast MR, including registration of serial dynamic images, segmentation and extraction of morphological features of breast lesions, and contrast uptake modeling, is also included. Recent advances in MRI, MRS, and automated image analysis have increased the utility of breast MR in diagnosis, screening, management, and therapy monitoring of breast cancer.

Efficient multilevel brain tumor segmentation with integrated bayesian model classification.

We present a new method for automatic segmentation of heterogeneous image data that takes a step toward bridging the gap between bottom-up affinity-based segmentation methods and top-down generative model based approaches. The main contribution of the paper is a Bayesian formulation for incorporating soft model assignments into the calculation of affinities, which are conventionally model free. We integrate the resulting model-aware affinities into the multilevel segmentation by weighted aggregation algorithm, and apply the technique to the task of detecting and segmenting brain tumor and edema in multichannel magnetic resonance (MR) volumes. The computationally efficient method runs orders of magnitude faster than current state-of-the-art techniques giving comparable or improved results. Our quantitative results indicate the benefit of incorporating model-aware affinities into the segmentation process for the difficult case of glioblastoma multiforme brain tumor.

Analysis of the brain-stem white-matter tracts with diffusion tensor imaging.

The authors have reviewed the diffusion tensor imaging (DTI) of the brain stem in 19 subjects, consisting of 15 normal volunteers and four multi-system atrophy patients. The study was performed with 1.5 T MRI scanners. DTI was correlated with an automated program allowing superposition of the structural anatomy. Axial, sagittal, and coronal images demonstrated major white-matter fibers within the brain stem, including cortico-spinal tracts, transverse pontine fibers, and medial lemniscus. Smaller fibers, such as medial longitudinal fascicles and central tegmental tracts are difficult to visualize. To identify the anatomical orientation of the brain stem, white-matter fibers will help us understand the different functional disease processes, and DTI will play an important role for the evaluation of the different white matter fibers in the brain stem.

Therapeutic approaches in arterial thrombosis.

The current standard of care for the treatment of arterial thrombosis includes anticoagulants and three classes of antiplatelet agents--aspirin, thienopyridines and glycoprotein IIb-IIIa antagonists. Although these drugs have had a significant impact on morbidity and mortality in several patient populations, up to 15% of the high risk patients with acute coronary syndrome continue to suffer from ischemic events. This problem may occur, in part, because the platelets in many patients are non-responsive to aspirin and clopidogrel. Murine models now indicate that platelets are not only responsible for arterial occlusion, they are also involved in the progression of atherosclerotic disease. New opportunities have emerged identifying potential targets and strategies for drug discovery suited to address these deficiencies by more effectively modulating platelet adhesion, thrombus growth, thrombus stability and the pro-inflammatory activity of platelets. In addition, a growing need has emerged for the development of bedside devices capable of bringing personalized medicine to patients being treated with antithrombotic drugs in order to measure the pharmacodynamic activities of new therapies, to assess the activities achieved by combined antithrombotic therapy, and to identify patients that fail to respond.

Histopathological changes in cases of aluminium phosphide poisoning.

Of a total of 205 poisoning deaths in our hospital in 2003, 83 cases were due to Aluminium phosphide poisoning and were further analyzed. Most vulnerable age group was 21-40 years and M:F ratio was 2:1. On naked eye examination, almost all the vital organs were found to be congested. On microscopic study, the liver showed central venous congestion, degeneration, haemorrhage, sinusoidal dilation, bile stasis, centrilobular necrosis, Kupffer cell hyperplasia, infiltration by mononuclear cells and fatty change. Microscopy of the lungs revealed alveolar thickening, oedema, dilated capillaries, collapsed alveoli and haemorrhage. In the kidney, changes were degeneration, infiltration, tubular dilation and cloudy swelling. Changes in the brain included congestion and coagulative necrosis and in the stomach, congestion and haemorrhage. Easy availability of this cheap and highly toxic substance was responsible for the sudden spurt of poisoning with aluminium phosphide.

Relationships between stem cells and cancer stem cells.

Stem cells have been shown to exist in a variety of tissues. Recent studies have characterized stem cell gene expression patterns, phenotypes, and potential therapeutic uses. One of the most important properties of stem cells is that of self renewal. This raises the possibility that some of the clinical properties of human tumors may be due to transformed stem cells. Similar signaling pathways may regulate self renewal in normal and transformed stem cells. These rare transformed stem cells may drive the process of tumorigenesis due to their potential for self renewal. There are important ramifications for clinical cancer treatment if the growth of solid tumors is at least partially dependent on a cancer stem cell population. In the cancer stem cell model, tumor recurrence may be due to the non-targeted stem cell compartment repopulating the tumor. If cancer stem cells can be prospectively identified and isolated, it should be possible to identify therapies that will selectively target these cells.

Quantitative assessment of parallel acquisition techniques in diffusion tensor imaging at 3.0 Tesla.

Single shot echo-planar based diffusion tensor imaging is prone to geometric and intensity distortions which scale with the magnetic field. Parallel imaging is a means of reducing these distortions while preserving spatial resolution. A quantitative comparison at 3 T of parallel imaging for diffusion tensor sequences using k-space (GRAPPA) and image domain (SENSE) reconstructions is reported here. Indices quantifying distortions, artifacts and reliability were compared for all voxels in the corpus callosum and showed that GRAPPA with an acceleration factor of 2 was the optimal sequence.

Age specific incidence rate and pathological spectrum of oral cancer in Allahabad.

BACKGROUND: Cancer of the oral cavity is one of the commonest cancers in India. Use of smokeless tobacco (Pan masala, Zarda etc ) is on the increase in North India and specially in Uttar Pradesh. AIMS: To assess the patients characteristics and histopathological subtypes of the oral cancer in our region. SETTINGS AND DESIGN: A single institutional retrospective study of 11 years from 1990 to 2000 was designed. Data was collected year wise using the tumour registry data. MATERIAL AND METHODS: A total of 40,559 biopsies were examined in the department during 1990-2000, out of which the oral cavity constituted 759 biopsies. The data was analysed with emphasis on age, sex, risk factors, site and histology. STATISTICAL ANALYSIS: The data was analysed utilizing the Kolomogroo-Smirnov two sample test. RESULTS: A comparison of the age specific incidence rates of oral cancer during 1990-2000 in Allahabad showed that the incidence was maximum in the 50-59 years age group and squamous cell carcinoma grade I was the most prevalent type. Of the total of 759 biopsies from oral cavity, 303 malignant cases. 232 (76.57%) were males and 71 (23.43% were females with a male to female ratio of 3.27:1. The tongue was the most frequently involved site--found in 42.57% cases. On an average, 63 new cases of oral cavity per annum were detected during this period. CONCLUSIONS: Properly structured site specific data like this can augment National Cancer Registry Programme (NCRP) and is an essential indicator for the magnitude and the pattern of the cancer problem in India Urgent public health measures like public education and oral cancer awareness are required to curb this avoidable epidemic.

A customizable MR brain imaging atlas of structure and function for decision support.

We present a MR brain atlas for structure and function (diffusion weighted images). The atlas is customizable for contrast and orientation to match the current patient images. In addition, the atlas also provides normative values of MR parameters (T1, T2 and ADC values). The atlas is designed on informatics principles to provide context sensitive decision support at the time of primary image interpretation. Additional support for diagnostic interpretation is provided by a list of expert created most relevant 'Image Finding Descriptors' that will serve as cues to the user. The architecture of the atlas module is integrated into the image workflow of a radiology department to provide support at the time of primary diagnosis.

Effect of anticoagulants and antiplatelet agents on platelet-mediated thrombin generation.

The present study was designed to determine the mechanism by which and extent to which antagonists of glycoprotein IIbIIIa (GPIIbIIIa or alpha beta ) or activated factor X (FXa) activity block tissue factor-initiated thrombin generation by prothrombinase complexes assembled on the surface of activated platelets. In the presence of high concentrations of GPIIbIIIa antagonists, which eliminate platelet aggregation but not activation, there is still a substantial amount of thrombin produced. In contrast, specific antagonists of the coagulation cascade lead to abolition of both thrombin generation and platelet aggregation. In addition, inhibitors with similar inhibitory activity (Ki) against purified human FXa require a much broader range of concentrations (a variation of 10 000-fold or more) to reduce the amount of thrombin produced in a platelet-rich plasma assay. At the doses tested, inhibitors with greater potency in prevention of thrombin production in the platelet-rich plasma assay were effective in vivo antithrombotics in an animal model system, whereas a lower potency compound did not reduce thrombus mass. Therefore, inhibition of FXa within platelet bound prothrombinase rather than inhibition of purified FXa in solution may be a better predictor of antithrombotic efficacy. In addition, all the studied anticoagulants fared better than the antiplatelet agents in reducing thrombin generation.

Molecular pathology of head and neck cancer.

Squamous cell carcinoma of the head and neck region (HNSCC) is the sixth most frequent cancer worldwide, comprising almost 50% of all malignancies in some developing nations. In the United States, 30,000 new cases and 8,000 deaths are reported each year. Survival rates vary depending on tobacco and alcohol consumption, age, gender, ethnic background, and geographic area. This variability reflects the multifactorial pathogenesis of the disease. Early detection and diagnosis has increased survival but the overall 5 year rate of 50% is among the lowest of the major cancers. Differences between normal epithelium and cancer cells of the upper aerodigestive tract arise from specific alterations in genes controlling DNA repair, proliferation, immortalization, apoptosis, invasion, and angiogenesis. These proteins include both tumor suppressors and activating oncogenes which regulate a wide variety of intracellular signaling pathways. Included in these pathways are growth factor receptors, signal transducers, and transcription factors which regulate DNA damage response, cell cycle arrest, and programmed cell death. In head and neck cancer, alterations of three signaling pathways occur with sufficient frequency and produce such dramatic phenotypic changes as to be considered the critical transforming events of the disease. These changes include mutation of the p53 tumor suppressor, inactivation of the cyclin dependent kinase inhibitor p16, and overexpression of epidermal growth factor receptor (EGFR). This review will focus on the molecular changes which occur in these pathways and how they contribute to the pathogenesis of HNSCC.

Frontotemporal reconstruction with hydroxyapatite cement and the radial forearm free flap.

BACKGROUND: Contemporary surgical reconstruction of extensive frontal and temporal bony and soft tissue defects requires the use of myocutaneous free flaps. These flaps are associated with donor site morbidity, lengthy operative time, and lack of rigid protection for the brain. To circumvent these problems, we introduce a new surgical technique for reconstruction of frontotemporal defects. OBJECTIVES: To evaluate and discuss hydroxyapatite and radial forearm free flap (RFFF) reconstructive options for patients with soft tissue and bony defects in the frontal and temporal regions after ablative cancer surgery. METHODS: Eight consecutive patients with extensive soft tissue and bony defects in the frontal and temporal regions underwent primary reconstruction with hydroxyapatite cement for replacement of bone, and the RFFF for soft tissue coverage. Patient follow-up ranged from 6 to 48 months. Outcome was determined in terms of immediate and delayed postoperative complications, donor site morbidity, and long-term aesthetic results. RESULTS: Excellent bony and soft tissue contour restoration was achieved in all patients. The bony and soft tissue volume was maintained throughout the follow-up period. One patient had a stroke. No other postoperative complications were encountered. Morbidity from RFFF harvest was minimum. CONCLUSIONS: The combination of hydroxyapatite cement and the RFFF is a viable alternative to the conventional myocutaneous free flap reconstruction of extensive frontotemporal defects. This technique provides excellent aesthetic results, provides rigid protection for the brain, produces minimal and well-tolerated donor site morbidity, and reduces operative time by avoiding intraoperative changes in patient position.