Breath-hold perfusion and permeability mapping of hepatic malignancies using magnetic resonance imaging and a first-pass leakage profile model

We have applied a novel pharmacokinetic model of the distribution of contrast media to dynamic contrast-enhanced MRI data from patients with hepatic neoplasms. The model uses data collected during the passage of a bolus of contrast medium and allows breath-hold image acquisition. The aims of the study were to investigate the feasibility of permeability mapping using the first pass technique and breath-hold acquisitions, and to examine the reproducibility of the technique and the effect of the liver's dual vascular supply on the assumptions of the model. Imaging was performed in 14 patients with hepatic neoplasms. Dynamic data clearly demonstrated differences in the timing and shape of the contrast medium concentration-time course curve in the systemic arterial and portal venous systems. Mapping of the arrival time (T(0)) of contrast medium allowed identification of tissue supplied by the hepatic arteries and portal vein. Hepatic tumours all showed typical hepatic arterial enhancement. Repeated measurements of endothelial permeability surface area product (k(fp)) and relative blood volume (rBV), performed in five patients, showed excellent reproducibility with variance ratios (V(r)) of 0.134 and 0.113, respectively. Measurement of enhancing tumour volume was also highly reproducible (V(r) = 0.096) and this was further improved by the use of T(0) maps to identify pixels supplied by the hepatic artery (V(r) = 0.026). Estimates of k(fp) and rBV in normal hepatic tissue supplied by the portal vein were highly inaccurate and these pixels were identified by use of the T(0) parameter and excluded from the analysis. In conclusion, dynamic MRI contrast enhancement combined with a pharmacokinetic model of the distribution of contrast media in the first pass allows us to produce highly reproducible parametric maps of k(fp) and rBV from hepatic tumours that are supplied by the hepatic arterial system using breath-hold acquisitions.     

Characterization of primary cell cultures as potential target cells for analysis of bovine cytotoxic T lymphocytes

In domestic animal species, assessment of cell-mediated immune responses to virus infection is hampered by the requirement for class I MHC compatibility between target and effector cells. Additional complicating factors can include an inability to infect target cells in vitro, or virus-induced lysis of infected target cells. One way to circumvent these problems is to use virus-mediated gene transfer to deliver individual viral genes to autologous primary target cells. Several primary bovine cell cultures were assessed as potential target cells for cytotoxic T lymphocyte (CTL) assays by measuring their levels of class I MHC expression and susceptibilities to retroviral gene delivery. High levels in both class I MHC expression and susceptibility to gene delivery were seen in adherent cell cultures isolated from peripheral blood (PBAC). PBAC, which arose as an outgrowth of adherent peripheral blood mononuclear cell cultures, had morphology, protein expression patterns, and response to functional assays characteristic of high endothelial cells. Expression of viral vector-delivered genes in PBAC cells was confirmed with a recombinant retrovirus carrying the green fluorescent protein (GFP) gene. The use of vector-mediated delivery of viral genes to bovine high endothelial cells is a promising method for assessment of cell-mediated immunity in cattle.     

Comparison of slide agglutination test and direct immunofluorescence assay for identification of Legionella isolates.

It is technically impractical for many clinical laboratories to use the direct immunofluorescence assay for identifying and serogrouping clinical isolates of Legionella. We compared the results obtained with the direct immunofluorescence assay with the results of a simple and less-demanding slide agglutination test for identifying 15 serogroups representing seven Legionella species. The slide agglutination test was in complete agreement with the direct immunofluorescence assay, and the serogroup to which 64 clinical isolates of Legionella belonged was correctly identified. With polyvalent, pooled antisera and absorbed, serogroup-specific antisera, the slide agglutination test is a useful alternative to the direct immunofluorescence assay in the diagnosis of Legionella infections and for studying the serological relationships of Legionella-like organisms.     

Effect of Fatty Acid Composition in Polysorbate 80 on the Stability of Therapeutic Protein Formulations

Pharmaceutical Research - Polysorbate excipients are commonly used as surfactants to stabilize therapeutic proteins in formulations. Degradation of polysorbates could lead to particle formation and...     

Ophthalmic Evaluation in Beta-Thalassemia

Objectives

To determine the association of ocular manifestations in beta-thalassemia with the patient’s age, blood transfusion requirements, average serum ferritin and dose and duration of iron chelation therapy.

Methods

Sixty multi-transfused beta thalassemia patients of 12 to 18 y of age on chelation therapy were included in this cross-sectional analysis. Structural and functional evaluation of the retina was done using Optical coherence tomography (OCT) and Electroretinography (ERG), including flash ERG and Pattern ERG (PERG). Routine ophthalmic examination and B scan of the eye was also done. Flash ERG a-waves and b-waves were recorded, however only a-wave amplitude was evaluated. Pattern ERG n35, n95 and p50 waves were recorded and p50 wave amplitude was evaluated. The a-wave on flash and p50 on pattern waves represent retinal photoreceptor epithelium (RPE) photoreceptor response, which is mainly affected in beta-thalassemia.

Results

Ocular changes were detected in 38.3% and a significant correlation was noted with increase in age (p = 0.045) but not with serum ferritin, transfusion requirements or chelation therapy. Refractive errors were found in 14 cases (23%), such as myopia with astigmatism in 13 (21.7%) and only myopia in 6 subjects (10%). OCT abnormality was noted in 1 patient (1.7%) who had thinning of central retina; right eye 132 μm and left eye 146 μm (n > 200 μm). Abnormalities were noted in a-wave amplitude on flash ERG in 20% of cases, while reduced p50 amplitude on PERG was noted in 15%.

Conclusions

A significant correlation was noted between ocular findings and increase in age, but not with serum ferritin, transfusion requirements or chelation therapy. ERG appears to be a promising tool for screening patients with beta-thalassemia and can serve as a follow-up test for evaluating retinal function.

     

Management of Non-Hodgkin Lymphoma: ICMR Consensus Document

Hitherto poor outcomes, paucity of data and heterogeneity in International approach to Pediatric NHL (Non-Hodgkin Lymphoma) prompted the need for guidelines for Indian population with vast variability in access, affordability and infrastructure across the country. These guidelines are based on consensus among the experts and best available evidence applicable to Indian setting. Evaluation of NHL should consist of easily doable and rapid tissue diagnosis (biopsy or flow cytometry of peripheral blood/malignant effusions), St Jude/IPNHLSS (International Pediatric Non-Hodgkin Lymphoma Staging System) and risk grouping with CSF (Cerebro-spinal fluid), bone marrow, whole body imaging [CECT (Contrast enhanced computerized tomography) ± MRI (Magnetic resonance imaging)] and blood investigations for LDH (Lactate dehydrogenase), TLS (Tumor lysis syndrome) and organ functions. Life threatening complications like SVCS (Superior vena cava syndrome)/Mediastinal syndrome and TLS need to pre-empted and promptly managed. All children with poor general condition, co-morbidities, metabolic or obstructive complications should receive a steroid or chemotherapy pro-phase first. For mature B-NHL (B cell – Non-Hodgkin lymphoma), in centres with good infrastructure and methotrexate levels, FAB-LMB-96 (French-American-British/Lymphomes Malins B) or BFM (Berlin-Frankfurt-Münster)-NHL-95 protocols may be used. In centres with limited infrastructure and/or no methotrexate levels; CHOP (Cyclophosphamide-hydroxydaunomycin-oncovin-prednisolone) (early stage) or MCP (Multi-centre protocol)-842 [all stages except CNS (Central nervous system) disease] may be used. Patients with poor early response should have escalated therapy. High-Risk B-NHL will benefit with addition of Rituximab to standard chemotherapy. Radiotherapy (RT) is not warranted. For lymphoblastic lymphoma, in centres with good infrastructure and methotrexate levels, BFM-95 protocol may be used. In centres with limited infrastructure and/or no methotrexate levels; modified MCP-841 with cytarabine, modified BFM-90 protocol with reduced-dose methotrexate or I-BFM 2009 protocol using Capizzi methotrexate may be considered. For ALCL (Anaplastic large cell lymphoma), in centres with good infrastructure and methotrexate levels, ALCL-99 protocol may be considered. In centres with limited infrastructure and/or no methotrexate levels; CHOP (limited-stage only), modified MCP-842 protocol or APO (Adriamycin-prednisolone-oncovin) regimen may be used.     

Pre-procedural scout radiographs are unnecessary for routine pediatric fluoroscopic examinations

Background

Although practice patterns vary, scout radiographs are often routinely performed with pediatric fluoroscopic studies. However few studies have evaluated their utility in routine pediatric fluoroscopy.

Objective

To evaluate the value of scout abdomen radiographs in routine barium or water-soluble enema, upper gastrointestinal (GI) series, and voiding cystourethrogram pediatric fluoroscopic procedures.

Materials and methods

We retrospectively evaluated 723 barium or water-soluble enema, upper GI series, and voiding cystourethrogram fluoroscopic procedures performed at our institution. We assessed patient history and demographics, clinical indication for the examination, prior imaging findings and impressions, scout radiograph findings, additional findings provided by the scout radiograph that were previously unknown, and whether the scout radiograph contributed any findings that significantly changed management.

Results

We retrospectively evaluated 723 fluoroscopic studies (368 males and 355 females) in pediatric patients. Of these, 700 (96.8%) had a preliminary scout radiograph. Twenty-three (3.2%) had a same-day radiograph substituted as a scout radiograph. Preliminary scout abdomen radiographs/same-day radiographs showed no new significant findings in 719 (99.4%) studies. New but clinically insignificant findings were seen in 4 (0.6%) studies and included umbilical hernia, inguinal hernia and hip dysplasia. No findings were found on the scout radiographs that would either alter the examination performed or change management with regard to the exam.

Conclusion

Pre-procedural scout abdomen radiographs are unnecessary in routine barium and water-soluble enema, upper GI series, and voiding cystourethrogram pediatric fluoroscopic procedures and can be substituted with a spot fluoroscopic last-image hold.