Molecular analysis of 11q13 breakpoints in multiple myeloma

The t(11;14)(q13;q32) chromosomal translocation, which is the hallmark of mantle cell lymphoma (MCL), is found in approximately 30% of multiple myeloma (MM) tumors with a 14q32 translocation. Although the overexpression of cyclin D1 has been found to be correlated with MM cell lines carrying the t(11;14), rearrangements of the BCL-1/cyclin D1 regions frequently involved in MCL rarely occur in MM cell lines or primary tumors. To test whether specific 11q13 breakpoint clusters may occur in MM, we investigated a representative panel of primary tumors by means of Southern blot analysis using probes derived from MM-associated 11q13 breakpoints. To this end, we first cloned the breakpoints and respective germ-line regions from a primary tumor and the U266 cell line, as well as the germ-line region from the KMS-12 cell line. DNA from 50 primary tumors was tested using a large panel of probes, but a rearrangement was detected in only one case using the KMS-12 breakpoint probe. Our results confirm previous findings that the 11q13 breakpoints in MM are scattered throughout the 11q13 region encompassing the cyclin D1 gene, thus suggesting the absence of 11q13 breakpoint clusters in MM.     

The Berlekamp-Massey Algorithm revisited

We propose a slight modification of the Berlekamp-Massey Algorithm for obtaining the minimal polynomial of a given linearly recurrent sequence. Such a modification enables to explain it in a simpler way and to adapt it to lazy evaluation. partially supported by the Galois Theory and Explicit Methods in Arithmetic Project HPRN-CT-2000-00114 partially supported by the European Union funded project RAAG CT-2001-00271     

Work-related ladder fall fractures: identification and diagnosis validation using narrative text

OBJECTIVE: To identify ladder-related fracture injuries and determine how ladder fall fractures differ from other ladder-related injuries. METHODS: Ladder-related fracture cases were identified using narrative text and coded data from workers' compensation claims. Potential cases were identified by text searches and verified with claim records. Injury characteristics were compared using proportionate injury ratios. RESULTS: Of 9826 ladder-related injuries, 7% resulted in fracture cases. Falls caused 89% of fractures and resulted in more medical costs and disability days than other injuries. Frequent mechanisms were ladder instability (22%) and lost footing (22%). Narrative text searches identified 17% more fractures than injury codes alone. Males were more likely to sustain a fall fracture than other injuries; construction workers were most likely, and retail workers were the least likely to sustain fractures. CONCLUSIONS: Fractures are an important injury from ladder falls, resulting more serious consequences than other ladder-related injuries. Text analysis can improve the quality and utility of workers compensation data by identifying and understanding injury causes. Proportionate injury ratios are also useful for making cross-group comparisons of injury experience when denominator data are not available. Greater attention to risk factors for ladder falls is needed for targeting interventions.     

Gamma dose from activation of internal shields in IRIS reactor

The International Reactor Innovative and Secure is a modular pressurised water reactor with an integral design. This means that all the primary system components, such as the steam generators, pumps, pressuriser and control rod drive mechanisms, are located inside the reactor vessel, which requires a large diameter. For the sake of better reliability and safety, it is desirable to achieve the reduction of vessel embrittlement as well as the lowering of the dose beyond the vessel. The former can be easily accomplished by the presence of a wide downcomer, filled with water, which surrounds the core region, while the latter needs the presence of additional internal shields. An optimal shielding configuration is under investigation, for reducing the ex-vessel dose due to activated internals and for limiting the amount of the biological shielding. MCNP 4C calculations were performed to evaluate the neutron and the gamma dose during operation and the 60Co activation of various shields configurations. The gamma dose beyond the vessel from activation of its structural components was estimated in a shutdown condition, with the Monte Carlo code FLUKA 2002 and the MicroShield software. The results of the two codes are in agreement and show that the dose is sufficiently low, even without an additional shield.     

Steel Hexagonal Honeycomb Core Equivalent Elastic Moduli for Bridge Deck Sandwich Panels

Glass fiber-reinforced polymer (GFRP) materials possess inherently high strength-to-weight ratios, but their effective elastic moduli are low relative to civil engineering (CE) construction materials. While elastic modulus may be comparable to that of some CE materials, the lower shear modulus adversely affects stiffness. As a result, serviceability issues are what govern GFRP deck design in the CE bridge industry. An innovative solution to increase the stiffness of a commercial GFRP reinforced-sinusoidal honeycomb sandwich panel was proposed; this solution would completely replace the GFRP honeycomb core with a hexagonal honeycomb core constructed from commercial steel roof decking. The purpose of this study was to perform small-scale tests to characterize the steel hexagonal honeycomb core equivalent elastic moduli in an effort to simplify the modeling of the core. The steel core equivalent moduli experimental results were compared with theoretical hexagonal honeycomb elastic modulus equations from the literature, demonstrating the applicability of the theoretical equations to the steel honeycomb core. Core equivalent elastic modulus equations were then proposed to model and characterize the steel hexagonal honeycomb as applicable to sandwich panel design. The equivalent honeycomb core will enable an efficient sandwich panel stiffness design technique, both for structural analysis methods (i.e., hand calculations) and finite-element analysis procedures.     

Comparison between noninvasive indices of baroreceptor sensitivity and the phenylephrine method in post-myocardial infarction patients

BACKGROUND: Depressed baroreflex sensitivity obtained by means of a phenylephrine test plays a prognostic role in patients with a previous myocardial infarction. Our purpose was to evaluate the correlation and agreement between the baroreflex sensitivity obtained with phenylephrine and that obtained by two noninvasive methods: the alpha-index and sequence analysis. METHODS AND RESULTS: The alpha-index was measured by means of the spectral analysis of RR and systolic blood pressure variabilities in both the high- and low-frequency bands; sequences were identified from simultaneously recorded time series in which the RR and systolic blood pressure concurrently increased or decreased. Noninvasive baroreflex sensitivity tests were performed during both spontaneous and controlled respiration. Fifty-two consecutive patients with recent myocardial infarction underwent the analyses. Although the correlations between phenylephrine and either of the noninvasive methods were always significant, those found during controlled respiration had the highest r values (r=.70). However, the limits of agreement calculated by means of the Bland and Altman method were wide for both noninvasive methods. CONCLUSIONS: The results obtained by means of noninvasive baroreflex sensitivity assessments should not be used in clinical practice as an alternative to those obtained by the phenylephrine method.     

Prognosis of myasthenia gravis: a retrospective study of 380 patients

The 9139 follow-up records of 438 myasthenia gravis (MG) patients were reviewed. Excluding those patients who were diagnosed 5 or more years after symptom onset (n = 37) and those who experienced only oculomotor symptoms throughout follow-up (n = 21), there were 380 patients. A survival analysis approach was used to assess the influence of prognostic factors on the following endpoints: (a) stable complete remission, (b) complete remission of at least 6 months and (c) pharmacological remission of at least 6 months. Early diagnosis was associated with a better prognosis with respect to all endpoints. Thymectomy also improved the prognosis but only for those patients without thymoma. Later MG onset was associated with a higher tendency to achieve pharmacological remission.     

Fixity of vocal cords and laryngocele in acromegaly

Acromegalic patients have a reduced life expectancy mainly due to cardio-, cerebrovascular and respiratory disorders and increased prevalence of neoplasias. Particularly, the pathogenesis of respiratory disorders in acromegalics is debated. Laryngeal abnormalities are not yet well clarified even if they are frequently involved in the occurrence of respiratory insufficiency. In this study, we report on a 65 year-old acromegalic male suffering from frequent and severe dyspnea attacks and clinical findings of respiratory upperway obstruction, besides the common acromegalic features. At the external examination of the larynx, a bilateral painless and soft mass, located in the laterocervical region under the hyoid bone, was detected. Fiberoptic laryngoscopy, showed bilateral swelling between the aryepiglottic fold and the false vocal cords, whose size increased during the expiration and the phonation, fixity of the vocal cords in paramedian position, with a marked reduction of the respiratory space and increase in arytenoid cartilage size and mucosal edema. Neck and mediastinum CT scan showed the presence of an air containing bilateral swelling, crossing the thyrohyoid membrane. Bilateral cricoarytenoidal joint chondrocalcification, associated to a mixed-type bilateral laryngocele, was diagnosed. Laryngoceles were both surgically removed and a left monolateral arytenoidectomy was performed, using fiberoptic microlaryngoscopy with CO2 laser. The clinical evaluation, one month later, confirmed the complete disappearance of dyspnea and a partial improvement of phonation. Three months later, laryngoscopy showed the bilateral restoration of vocal cords motility and a significant improvement of phonation. This case presents an uncommon and severe respiratory problem in acromegaly such as the fixity of vocal cords associated to laryngocele. Circulating GH and IGF-I hypersecretion caused edema and laxity of laryngeal mucosa as well as bilateral ankylosis of cricoarytenoidal joints. The use of CO2 laser technique via micro-laryngoscopy successfully resolved laryngeal abnormalities.     

Growth hormone and heart performance. A novel mechanism of cardiac wall stress regulation in humans

OBJECTIVES: This study was designed to assess systolic wall stress and ventricular function in patients with deranged growth hormone secretion, in an attempt to elucidate the mechanisms of growth hormone interaction with heart performance. DESIGN: A case-control study. SUBJECTS: Thirty patients with active acromegaly, free of diabetes mellitus and coronary artery disease, and 25 subjects with congenital growth hormone deficiency were studied. Twelve growth hormone-deficient subjects were reevaluated after 12 months of recombinant human growth hormone therapy. Two groups of 30 normal subjects each were used as controls for the acromegalic and growth hormone-deficient patients, respectively. RESULTS: In the acromegalics, end-systolic wall stress was reduced (-20%; P < 0.01) due to ventricular wall thickening (+ 26%; P < 0.001), whereas cardiac output was significantly increased (+ 20%; P < 0.01). The velocity of fibre shortening was unchanged. In growth hormone-deficient subjects, end-systolic wall stress was markedly increased (+ 38%; P < 0.001) due to a significant reduction of ventricular wall thickness (- 28%; P < 0.001), whereas cardiac output was significantly decreased (-44%; P < 0.001). Replacement therapy with recombinant human growth hormone produced a partial correction of wall thickness and stress. Consequently, systolic performance and cardiac output improved significantly. CONCLUSION: This study demonstrates that growth hormone plays a role in the control of cardiac wall stress and performance through a mechanism mediated by the effect of growth hormone on myocardial tissue growth. The data may have therapeutic implications in cardiac diseases that lead to heart failure.