Emergence of translocation t(9;11)-positive leukemia during treatment of childhood acute lymphoblastic leukemia

Therapy-related acute myeloid leukemia (t-AML) characterized by the t(9;11)(p22;q23) translocation is one of the most frequent secondary malignancies. The timing of the initiation of translocation and of development of the malignant t(9;11) clone during chemotherapy is presently unknown. In the present study, we backtracked bone marrow samples from three children during treatment for acute lymphoblastic leukemia (ALL). Two patients developed a t(9;11)-positive t-AML 19 and 30 months after therapy start, whereas the third patient, diagnosed with a rare t(9;11)-positive ALL, suffered from an ALL relapse 23 months after initial diagnosis. The genomic MLL-MLLT3 (MLL-AF9) fusion site was amplified by a multiplex, nested long-range PCR and used as a clonal marker for quantification of the MLL-MLLT3-positive cells during chemotherapy. The t(9;11)-positive clone was detectable 13 and 18 months after therapy start in both t-AML cases, which was 6-12 months before clinical diagnosis of the secondary malignancy. In the t(9;11)-positive ALL patient, the identical leukemic clone reoccurred during maintenance therapy after a short molecular remission, 8 months before clinically overt ALL relapse. The time course and characteristics of the genomic breakpoints in the present t-AML cases support the hypothesis of translocation formation as a result of defective breakage repair after topoisomerase II cleavage.     

An unusual origin of the celiac trunk and the superior mesenteric artery in the thorax

The authors report a case of a 44‐year‐old male found to have unusual origins of the celiac trunk (CT) and superior mesernteric artrery (SMA) as revealed by routine multidetector computed tomograph (MDCT) angiography. The CT and SMA originate from the thoracic aorta (TA) 21 mm and 9 mm above the aortic hiatus, respectively. The median arcuate ligament (MAL) is located at the level of the L1–L2 intervertebral disc. The course of the CT descends in the thoracic cavity making a 14° acute downward angle in front of the TA; below the level of the MAL, the CT descends, making an angle of 47°. The course of the SMA descends at both the thoracic and abdominal level making an angle of 17°, and having an aortomesenteric distance of 9 mm at the level of the third part of the duodenum. In the present case, the supradiaphragmatic origin of the CT and the SMA was determined by their incomplete caudal descent, associated with a pronounced apparent descent of the diaphragm. A thoracic origin of the CT and SMA and the acute downward aortomesenteric angle (17°) associated with a reduced aortomesenteric distance at the level of the third part of the duodenum (9 mm), although no clinical signs are present, may predispose the patient to develop simultaneously a triple syndrome: the compression of CT by MAL (celiac axis compression syndrome), the compression of SMA by MAL (superior mesenteric artery compression syndrome), and the compression of the duodenum by the SMA (superior mesenteric artery syndrome). Clin. Anat. 26:975–979, 2013. © 2013 Wiley Periodicals, Inc.     

Influence of various irradiation processes on the mechanical properties and polymerisation kinetics of bulk-fill resin based composites

ObjectivesTo assess the effect of irradiation time and distance of the light tip on the micro-mechanical properties and polymerisation kinetics of two bulk-fill resin-based composites at simulated clinically relevant filling depth.MethodsMicro-mechanical properties (Vickers hardness (HV), depth of cure (DOC) and indentation modulus (E)) and polymerisation kinetics (real-time increase of degree of cure (DC)) of two bulk-fill resin-based composites (Tetric EvoCeram^® Bulk Fill, Ivoclar Vivadent and x-tra base, Voco) were assessed at varying depth (0.1–6 mm in 100 μm steps for E and HV and 0.1, 2, 4 and 6 mm for DC), irradiation time (10, 20 or 40 s, Elipar Freelight2) and distances from the light tip (0 and 7 mm). Curing unit's irradiance was monitored in 1 mm steps at distances up to 10 mm away from the light tip on a laboratory-grade spectrometer.ResultsMultivariate analysis (α = 0.05), Student's t-test and Pearson correlation analysis were considered. The influence of material on the measured mechanical properties was significant (η² = 0.080 for E and 0.256 for HV), while the parameters irradiation time, distance from the light tip and depth emphasise a stronger influence on Tetric EvoCeram^® Bulk Fill. The polymerisation kinetics could be described by an exponential sum function, distinguishing between the gel and the glass phase. The above mentioned parameters strongly influenced the start of polymerisation (gel phase), and were of less importance for the glass phase.ConclusionsBoth materials enable at least 4 mm thick increments to be cured in one step under clinically relevant curing conditions.Clinical significanceThe susceptibility to variation in irradiance was material dependent, thus properties measured under clinically simulated curing conditions might vary to a different extent from those measured under ideal curing conditions.     

Best Clinical Practice in Botulinum Toxin Treatment for Children with Cerebral Palsy

Botulinum toxin A (BoNT-A) is considered a safe and effective therapy for children with cerebral palsy (CP), especially in the hands of experienced injectors and for the majority of children. Recently, some risks have been noted for children with Gross Motor Classification Scale (GMFCS) of IV and the risks are substantial for level V. Recommendations for treatment with BoNT-A have been published since 1993, with continuous optimisation and development of new treatment concepts. This leads to modifications in the clinical decision making process, indications, injection techniques, assessments, and evaluations. This article summarises the state of the art of BoNT-A treatment in children with CP, based mainly on the literature and expert opinions by an international paediatric orthopaedic user group. BoNT-A is an important part of multimodal management, to support motor development and improve function when the targeted management of spasticity in specific muscle groups is clinically indicated. Individualised assessment and treatment are essential, and should be part of an integrated approach chosen to support the achievement of motor milestones. To this end, goals should be set for both the long term and for each injection cycle. The correct choice of target muscles is also important; not all spastic muscles need to be injected. A more focused approach needs to be established to improve function and motor development, and to prevent adverse compensations and contractures. Furthermore, the timeline of BoNT-A treatment extends from infancy to adulthood, and treatment should take into account the change in indications with age.     

Protective effects of silymarin on epirubicin-induced mucosal barrier injury of the gastrointestinal tract

Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the protective effects of silymarin on epirubicin-induced mucosal barrier injury in CD-1 mice. Immunohistochemical activity of both pro-apoptotic Bax and anti-apoptotic Bcl-2 markers, together with p53, cyt-P450 expression and DNA damage analysis on stomach, small intestine and colon were evaluated. Our results indicated stronger expression for cyt P450 in all analyzed gastrointestinal tissues of Epi group, which demonstrate intense drug detoxification. Bax immunopositivity was intense in the absorptive enterocytes and lamina connective cells of the small intestine, surface epithelial cells of the stomach and also in the colonic epithelium and lamina concomitant with a decreased Bcl-2 expression in all analyzed tissues. Epirubicin-induced gastrointestinal damage was verified by a goblet cell count and morphology analysis on histopathological sections stained for mucins. In all analyzed tissues, Bax immunopositivity has been withdrawn by highest dose of silymarin concomitant with reversal of Bcl-2 intensity at a level comparable with control. p53 expression was found in all analyzed tissues and decreased by high dose of silymarin. Also, DNA internucleosomal fragmentation was observed in the Epi groups for all analyzed tissues was almost suppressed at 100?mg/kg Sy co-treatment. Histological aspect and goblet cell count were restored at a highest dose of Sy for both small and large intestine. In conclusion, our findings suggest that silymarin may prevent cellular damage of epirubicin-induced toxicity and was effective in reducing the severity indicators of gastrointestinal mucositis in mice.     

Inflammatory markers in acute myocardial infarction and the correlation with the severity of coronary heart disease

IntroductionThe inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established.ObjectivesThe study investigates the levels of C reactive protein (CRP), interleukin 1β (IL-1β) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group.ResultsIn the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1β showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, p=.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= −0.43, p=.05). IL-1β weakly correlated with the severity of coronary lesions (rho =0.29, p=.02) and strongly with LVEF (rho= −0.8, p=.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, p=.01) and with the severity of coronary atherosclerosis (rho= −0.41, p=.003).ConclusionsCRP, IL-1β and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event.     

Predicting transmitted irradiance through CAD/CAM resin composite crowns in a simulated clinical model

ObjectiveTo predict the clinically relevant transmitted irradiance that is available for luting when a CAD/CAM restoration is inserted. The influence of irradiance, exposure distance, light curing unit (LCU) angulation and direction of polymerization is analyzed when curing through crowns of different thicknesses.MethodsThree modern CAD/CAM resin-based composites (RBCs) were used to produce 45 crown-shaped specimens. The distance between fissure and crown base was set at 1.0, 1.5 and 2.0 mm (n = 5). Transmitted irradiance, while using a violet-blue LCU, was measured with a photo-spectrometer. 180 exposure conditions per specimen were investigated by variation in LCU curing mode, angulation, exposure distance and direction. Data was analyzed using univariate ANOVA followed by Tukey HSD (α = 0.05) and comparison of 95% confidence intervals.ResultsThe CAD/CAM-RBC’s decadic absorption coefficient ranges from 0.317 mm^?1 to 0.387 mm^?1 and the reflection correcting factor for crowns ranges from 0.305 to 0.337. Transmitted irradiance decreases significantly with increasing exposure distance and decreasing incident irradiance. For tilt angles greater than 10°, transmitted irradiances are significantly reduced (?11% for 20°, ?23% for 30°). Significantly lowest transmitted irradiances were measured for vestibular curing direction (up to ?15%).SignificanceA calculation model can predict the transmitted irradiance through a CAD/CAM restoration in dependence of restoration thickness and radiant emittance. The practitioner can be supported by this model to adapt material choice of dental restoration and adhesive system to the individual situation. Variation in exposure conditions shows negative effect on the transmission of light and should be limited.     

The long-term consequence of salivary contamination at various stages of adhesive application and clinically feasible remedies to decontaminate

Clinical Oral Investigations - To analyse the bond quality in dentine post-ageing after salivary contamination and decontamination at different stages of dental adhesive application. A total of...     

Treatment and outcomes of acute coronary syndrome in the cancer population

Background:

Randomized trials have established the benefit of medical therapy and revascularization in the treatment of acute myocardial infarction (MI). Cancer and cardiovascular disease are the 2 most common diseases worldwide. In clinical practice, cancer patients are frequently afflicted with MI. The benefit of medical and/or revascularization therapy in the cancer population with MI is less well known.

Hypothesis:

Medical and revascularization therapy reduces mortality in cancer patients with MI.

Methods:

After approval by the institutional review board, we retrospectively reviewed all patients with a discharge diagnosis of acute MI who were admitted to the University of Texas MD Anderson Cancer Center between December 2000 and October 2006 and evaluated the association between cardiac treatments with survival outcomes.

Results:

A total of 456 patients with a discharge diagnosis of acute MI were identified and included in the study, of which 386 had non–ST‐segment elevation MI (NSTEMI) and 70 had ST‐segment elevation MI (STEMI). Compared with patients with NSTEMI, patients who had STEMI were more often prescribed aspirin (66% vs 43%; P = 0.004), β‐blockers (61% vs 46%; P = 0.018), and thrombolytic therapy (9% vs 0.3%; P = 0.0001). In the multivariable analysis, aspirin use was associated with a 23% decreased risk of death (hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.60‐0.98, P = 0.033) and β‐blocker use was associated with a 36% decreased risk of death (HR: 0.64, 95% CI: 0.51–0.81, P = 0.0002). Statins (HR: 0.82, P = 0.18) and catheter‐based revascularization (HR: 0.57, P = 0.09) did not have an impact on the risk of death. Compared with patients with limited cancer, advanced cancer patients were twice as likely to die (HR: 2.12, 95 CI: 1.47–3.04, P < 0.0001). Previous chemotherapy (P = 0.005) and chest radiotherapy (P = 0.017) were associated with increased 1‐year mortality, whereas hyperlipidemia (P = 0.018) was protective.

Conclusions:

In this study of cancer patients with MI, medical therapy with aspirin and β‐blockers was associated with improved survival. The authors have no funding, financial relationships, or conflicts of interest to disclose.