Budesonide versus mesalamine for maintaining remission in patients refusing other immunomodulators for steroid-dependent Crohn's disease.

BACKGROUND & AIMS: To compare the efficacy of controlled-release budesonide capsules with that of mesalamine for maintaining remission and improving quality of life (QOL) in patients with steroid-dependent Crohn's disease. METHODS: Fifty-seven patients (25 men; mean age, 32 +/- 10.1 yr) with quiescent steroid-dependent Crohn's ileitis, ileocolitis, or colitis (Crohn's disease activity index <150) entered a prospective, investigator-blind trial. Patients were eligible for treatment with azathioprine but had not consented or had developed side effects. Patients were randomized to receive budesonide 6 mg/day (n = 29) or mesalamine 1 g 3 times/day (n = 28). Follow-up assessments were made every 2 months for up to 1 year or until relapse. At each visit, quality of life (QOL) was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: There were no significant differences in baseline clinical characteristics between the study groups. The 1-year relapse rate was significantly lower in the budesonide group than in the mesalamine group (55% vs. 82%; 95% confidence interval, 12.4%-41%; P = 0.045). Patients assigned to budesonide also remained in remission longer (241 +/- 114 days vs. 147 +/- 117 days; 95% confidence interval, 32.7-155.3 days; P = 0.003). Compared with mesalamine, budesonide treatment also was associated with a better QOL throughout the study (mean total IBDQ scores 165 +/- 36 vs. 182 +/- 28, respectively; 95% confidence interval, -0.4 to 34.4, P = 0.0001). This advantage was confirmed in patients' self-assessed QOL scores. CONCLUSIONS: Over a 1-year period, controlled-release budesonide was significantly more effective than mesalamine for maintaining remission and improving the QOL of patients with steroid-dependent Crohn's disease.     

Dosimetry comparison of 192Ir sources

192Ir sources besides being widely utilized in the field of conventional brachytherapy also find use in contemporary peripheral and coronal intravascular applications. In this study, the same Monte Carlo simulation code and input data were used to investigate differences between the dose rate distributions of the most commonly used 192Ir sources in the cm and mm distance range. Findings are discussed in view of differences in source and encapsulation dimensions as well as structural details. Results are presented in the AAPM TG-43 formalism, as generalized by AAPM TG-60, for five 192Ir HDR source designs as well as an LDR seed and an LDR wire source. Dose rate constants of the sources at r0 = 1 cm and r0 = 2 mm were found proportional to the corresponding geometry factors along the transverse source bisectors and an equation of the form lambda r0(cGyh(-1) U(-1)) = 1.12 x G(r0,90 degrees) provides results within clinical accuracy (less than 2%) for any 192Ir source. Radial dose functions do not depend significantly on source and encapsulation geometry and agree within 2% with that of a point 192Ir source. Anisotropy is of importance for accurate dosimetry at the cm distance range but it does not affect dose rate in the mm distance range significantly. At such short radial distances the source geometry factor defines the shape of isodose lines. Dose uniformity at given distances from the sources is strongly dependent on source dimensions as indicated by dose rate profiles in polar and Cartesian coordinates.     

Dosimetry close to an 192Ir HDR source using N-vinylpyrrolidone based polymer gels and magnetic resonance imaging

In this work, the utilization of polymer gel-MRI dosimetry for measurements at distances relevant to clinical brachytherapy and intravascular applications [i.e., in the mm range, where steep three-dimensional (3-D) dose gradients exist] is investigated using N-vinylpyrrolidone-based gels. Transverse axis radial dose distributions, dose distributions parallel to the source axis, and 2-D dose distributions around the commonly used microSelectron 192Ir HDR source are measured for single source dwell position irradiations. Experimental results are found in good agreement with verified Monte Carlo calculations, even for distances less than 3 mm from the source. The effect of various MRI parameters, such as slice thickness, slice mispositioning, and in-plane resolution, on the accuracy of the method is also investigated. Possible limitations of the method are discussed, and its' overall potential in brachytherapy dosimetry is evaluated. Experimental 2-D dose distributions for an intravascular application following the Paris irradiation protocol are compared to corresponding commercial treatment planning system calculations. Results suggest that polymer gel-MRI dosimetry is capable of experimentally verifying dose distributions in relevant clinical intravascular applications.     

Relative output factor measurements of a 5 mm diameter radiosurgical photon beam using polymer gel dosimetry

Besides the fine spatial resolution inherent in polymer gel-magnetic resonance imaging (MRI) dosimetry, the method also features the potential for multiple measurements of varying sensitive volume in a single experiment by integrating results in MRI voxels of finite dimensions (i.e., in plane resolution by slice thickness). This work exploits this feature of polymer gel dosimetry to propose an experimental technique for relative output factor (OF) measurements of small radiosurgical beams. Two gel vials were irradiated with a 5 and 30 mm diameter 6 MV radiosurgery beam and MR scanned with the same slice thickness and three different in plane resolutions. Using this experimental data set, 5 mm OF measurements with the PinPoint ion chamber are simulated by integrating results over a sensitive volume equal to that of the chamber. Results are found in agreement within experimental uncertainties with actual PinPoint measurements verifying the validity of the proposed experimental procedure. The polymer gel data set is subsequently utilized for OF measurements of the 5 mm beam with varying sensitive volume to discuss the magnitude of detector volume averaging effects. Seeking to correct for volume averaging, results are extrapolated to zero sensitive volume yielding a 5 mm OF measurement of (0.66+/-5%). This result compares reasonably with corresponding ionometric and radiographic film measurements of this work and corresponding, limited, data in the literature. Overall, results suggest that polymer gel dosimetry coupled with the proposed experimental procedure helps overcome not only tissue-equivalence and beam perturbation implications but also volume averaging and positioning uncertainties which constitute the main drawback in small radiosurgical beam dosimetry.     

Expression of Epstein-Barr virus latent membrane protein-1 in Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma: associations with presenting features, serum interleukin 10 levels, and clinical outcome.

PURPOSE: EBV-latent membrane protein-1 (LMP-1) is often expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's lymphoma (cHL), but its clinical significance is controversial. We correlated LMP-1 with presenting features, including serum interleukin 10 levels and clinical outcome. EXPERIMENTAL DESIGN: Patients were eligible if they had biopsy-proven cHL, were untreated, HIV-1 negative, and had available archival tissue. LMP-1 expression was determined by immunohistochemistry. RESULTS: We identified 577 patients with cHL with a median age of 30 years, 55% of whom were male. LMP-1 was expressed in HRS cells of 124 patients (21%) and was detected in 78 of 461 (17%) patients with nodular sclerosis compared with 44 of 112 (39%) with mixed cellularity (P < 0.001 by Fisher's exact test). Patients with tumors with LMP-1-positive HRS cells had higher serum interleukin 10 levels (P = 0.009 by Mann-Whitney test). For the 303 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens, the 5-year failure-free survival (FFS) for those with LMP-1-positive tumors was 74% compared with 81% for those with LMP-1-negative tumors (P = 0.23, by log-rank test). Overall survival (OS) at 5 years for patients with LMP-1-positive tumors was 90 versus 91% for patients with LMP-1-negative tumors (P = 0.8 by log-rank test). Expression of LMP-1 was not associated with different FFS and OS in patients treated with other regimens or with radiotherapy alone. CONCLUSIONS: LMP-1 was expressed by HRS cells in 21% of cHL and correlated with mixed cellularity type and higher serum interleukin 10 levels. The presence of LMP-1 was not associated with FFS or OS in uniformly treated patients.     

Fructose-Containing Sugars and Cardiovascular Disease

Cardiovascular disease (CVD) is the single largest cause of mortality in the United States and worldwide. Numerous risk factors have been identified for CVD, including a number of nutritional factors. Recently, attention has been focused on fructose-containing sugars and their putative link to risk factors for CVD. In this review, we focus on recent studies related to sugar consumption and cardiovascular risk factors including lipids, blood pressure, obesity, insulin resistance, diabetes, and the metabolic syndrome. We then examine the scientific basis for competing recommendations for sugar intake. We conclude that although it appears prudent to avoid excessive consumption of fructose-containing sugars, levels within the normal range of human consumption are not uniquely related to CVD risk factors with the exception of triglycerides, which may rise when simple sugars exceed 20% of energy per day, particularly in hypercaloric settings.     

A morphometric study of bone marrow angiogenesis in hairy cell leukaemia with clinicopathological correlations

Bone marrow angiogenesis has recently been implicated in the pathophysiology and course of various haematological malignancies. Little is known, however, about the significance of this phenomenon in hairy cell leukaemia (HCL). We evaluated various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemistry, in the bone marrow of 44 patients with typical HCL, before and after treatment with interferon-alpha (IFN-alpha). Overall, bone marrow from 103 HCL patients and 20 controls was examined. Microvessel density (MVD) and several size- and shape-related parameters were quantified in the region of most intense vascularization using image analysis. MVD, size-related parameters and the percentage of branching microvessels were higher in HCL than in controls. Likewise, perimeter counts were higher in partial/non-responders than in complete responders. Achievement of complete response was accompanied by smaller calibre microvessels. IFN-alpha induced a decrease in MVD and branching values in cases with diffuse marrow involvement. In univariate analysis, progression-free survival was adversely affected by MVD, branching and major axis length. Multivariate analysis indicated that MVD/branching independently affected progression-free survival and the likelihood of complete response. Our data suggest that the generation of bone marrow microvessels indicated an increased risk of progression and IFN-alpha treatment failure in HCL. Furthermore, the prognostic significance of angiogenesis requires the concomitant assessment of MVD and the complexity of the microvascular network.     

Ida-FLAG plus imatinib mesylate-induced molecular remission in a patient with chemoresistant Ph1+ acute myeloid leukemia

Imatinib mesylate is a potent, selective inhibitor of the tyrosine kinase activity of bcr-abl,which is now established as the state-of-the-art treatment for chronic, accelerated or even blastic phase of Philadelphia-positive [Ph(1)(+)] chronic myelogenous leukemia. It is also active in Ph(1)(+) acute lymphoblastic leukemia, but its role in Ph(1)(+) acute myeloid leukemia (AML) is less well investigated. We report here a patient with chemoresistant Ph(1)(+) AML, who responded promptly to one cycle of Ida-FLAG second-line chemotherapy by achieving complete morphologic, immunophenotypic, and cytogenetic remission but not a molecular one. The addition of imatinib mesylate led to a molecular remission, which is sustained for 10 months so far.