Impact of treatment on the outcome of acute myeloid leukemia with inversion 16: a single institution's experience.

To identify treatment factors that may affect the survival of children with inv(16)(p13.1q22), we compared the outcomes of 19 patients with this genetic feature treated at our institution during two treatment eras. Nine patients were treated during era 1 (1980 to 1987), and 10 were treated during era 2 (1988 to 1996). All entered complete remission (CR) with induction therapy. Eight of the nine children treated in era 1 died, seven of relapsed leukemia. In contrast, three of 10 patients treated during era 2 have died, all of non-disease-related causes. Event-free survival (EFS) estimates were significantly higher for patients treated during era 2 than for those treated during era 1 (P = 0.03); the 6-year estimates were 70 +/- 15% (s.e.) and 11 +/- 7%, respectively. Era 2 treatment protocols differed from those of era 1 in their use of higher doses of cytarabine and etoposide during induction and consolidation chemotherapy and in their use of 2-chlorodeoxyadenosine (2-CDA). These results suggest that dose intensification of cytarabine benefits children with AML and inv(16), as is the case in adults. They also suggest that dose intensification of etoposide and addition of 2-CDA may also offer an advantage. This study underscores the dependence of the prognostic impact of cytogenetic features on the efficacy of treatment.     

Regulation of primary Strongyloides ratti infections in mice: a role for interleukin-5.

C57BL/6 mice genetically deficient in interleukin-5 (IL-5-/-) and normal C57BL/6 (IL-5+/+) mice were infected with larvae of a homogonic strain of the nematode Strongyloides ratti. In primary infections both male and female IL-5-/- mice released two to four times more eggs and larvae than IL-5+/+ mice. IL-5-/- mice harboured about 60% more intestinal worms, which were more fecund, than IL-5+/+ mice. The duration of the infection was similar in normal and IL-5-deficient mice. Both IL-5-/- and IL-5+/+ mice resisted a secondary infection. IL5-/- mice lost more weight during the infection than normal mice and took longer to regain their initial weight after expelling the worms. The number of eosinophils increased in the bone marrow, peritoneal cavity and small intestine of IL-5+/+ mice, but not IL-5-/- mice, following infection. No significant differences between infected IL-5+/+ and IL-5-/- mice in mast cells or other leucocytes were observed in the peritoneal cavity. Thus, IL-5 functions to protect the host in a primary infection of S. ratti by limiting the number and fecundity of worms establishing in the small intestine. This protection is correlated with elevated blood and tissue eosinophilia which occurs in normal mice but not in IL-5-/- mice.     

Multiple telomeric associations of a trisomic whole q arm of chromosome 1 in a child with acute lymphoblastic leukemia

The results of cytogenetic analysis of bone marrow cells from a 13-year-old boy with acute lymphoblastic leukemia (ALL) are described. Initial analysis of aspirated bone marrow disclosed ALL FAB-L1 morphology, common (Ia+, cALLa+) immunophenotype and a complex abnormal karyotype. The majority of leukemic cells showed unbalanced translocations that resulted in complete trisomy of the long arm of chromosome #1 as the common denominator. The heterochromatic region of chromosome #1 (1qh) was associated with the telomeres of whole chromosomes #2, #13, and #16 in 28% of the 36 metaphases completely analyzed. Telomeric association is a very rare event and this is only the second known report of its occurrence associated with ALL wherein the 1qh region is attached to the telomeres of different chromosomes, resulting in trisomy of the whole 1q arm.     

The effects of smoking-related sensory cues on psychological stress

Previous studies have shown that the sensory cues of cigarette smoking are important for smoking satisfaction and craving reduction. Sensory cues in the absence of pharmacological doses of nicotine have been found to be moderately satisfying and to reduce craving. The current study was conducted to determine if administration of the sensory cues of cigarette smoking with minimal nicotine would also provide relief from mild anxiety associated with anticipation of a difficult anagram test. This test has previously been shown to be sensitive to the anxiety relieving effects of cigarette smoking. Compared to the placebo control condition, the sensory condition caused a significant alleviation of the stress as measured by components of the Spielberger scale for anxiety. The addition of cigarette smoke containing 0.5 mg of nicotine to the sensory cues caused a slight though nonsignificant enhancement of the stress alleviation. These results demonstrate that sensory cues of smoking can provide similar effects as nicotine containing cigarettes with regard to stress alleviation. Previous studies had shown that sensory cues are important for the consumptive aspects of smoking (i.e., smoking satisfaction and craving reduction). The current study shows that sensory cues are important for other effects of smoking as well.     

Association between sagittal alignment and loads at the adjacent segment in the fused spine: a combined clinical and musculoskeletal modeling study of 205 patients with adult spinal deformity

Purpose

Sagittal malalignment is a risk factor for mechanical complications after surgery for adult spinal deformity (ASD). Spinal loads, modulated by sagittal alignment, may explain this relationship. The aims of this study were to investigate the relationships between: (1) postoperative changes in loads at the proximal segment and realignment, and (2) absolute postoperative loads and postoperative alignment measures.

Methods

A previously validated musculoskeletal model of the whole spine was applied to study a clinical sample of 205 patients with ASD. Based on clinical and radiographic data, pre-and postoperative patient-specific alignments were simulated to predict loads at the proximal segment adjacent to the spinal fusion.

Results

Weak-to-moderate associations were found between pre-to-postop changes in lumbar lordosis, LL (r =  − 0.23, r =  − 0.43; p < 0.001), global tilt, GT (r = 0.26, r = 0.38; p < 0.001) and the Global Alignment and Proportion score, GAP (r = 0.26, r = 0.37; p < 0.001), and changes in compressive and shear forces at the proximal segment. GAP score parameters, thoracic kyphosis measurements and the slope of upper instrumented vertebra were associated with changes in shear. In patients with T10-pelvis fusion, moderate-to-strong associations were found between postoperative sagittal alignment measures and compressive and shear loads, with GT showing the strongest correlations (r = 0.75, r = 0.73, p < 0.001).

Conclusions

Spinal loads were estimated for patient-specific full spinal alignment profiles in a large cohort of patients with ASD pre-and postoperatively. Loads on the proximal segments were greater in association with sagittal malalignment and malorientation of proximal vertebra. Future work should explore whether they provide a causative mechanism explaining the associated risk of proximal junction complications.

     

Experimental Study on Metal Parts under Variable 3D Printing and Sintering Orientations Using Bronze/PLA Hybrid Filament Coupled with Fused Filament Fabrication

Producing metal parts from Fused Filament Fabrication (FFF) 3D printing coupled with a metal/polymer hybrid filament, considering the advantages of high-performance and low cost, has generated considerable research interest recently. This paper addresses the studied relationship between variable printing/sintering directions and the properties of the sintered metal parts. It was shown that the printing directions played a significant role in determining the properties of final products, such as shrinkage, tensile stress, and porosity. The shrinkage in the layer direction because of anisotropic behavior is more minor than in the other dimensions. The microstructural analysis indicated that the printing directions had influenced the form and position of porosity on the produced metal parts. Most porosities occurred on the surfaces printed parallel to the printing bed. Furthermore, the sintering orientations had no possible benefits for dimension shrinkage, weight shrinkage, density, and porosity position of produced metal parts. However, the sintering direction “upright” resulted in parting lines inside the sintered tensile samples and made them fragile. The best printing-sintering combination was “on-edge-flat”.     

Lack of Evidence for Crossover Fatigue with Plantar Flexor Muscles

The occurrence and mechanisms underlying non-local or crossover muscle fatigue is an ongoing issue. This study aimed to investigate crossover fatigue of the plantar flexor muscles. Sixteen recreationally active males (n = 6) and females (n = 10) visited the laboratory for four sessions and performed a single 5-s pre-test maximal voluntary isometric contraction (MVIC) with each plantar flexors muscle. Thereafter, the fatigue intervention involved two 100-s MVICs (60-s recovery) with their dominant plantar flexors or rested for 260-s (control). Subsequently, in two separate sessions, Hoffman reflexes (H-reflex) were evoked in the non-dominant, non-exercised, leg before and following the dominant leg fatigue or control intervention (Fatigue-Reflex and Control-Reflex conditions). MVIC forces and volitional (V)-waves were monitored in the non-dominant leg in the other two sessions (Fatigue-MVIC and Control-MVIC) before and after the intervention (fatigue or control) as well as during 12 repeated MVICs and immediately thereafter. Despite the force reduction in the dominant leg (42.4%, p = 0.002), no crossover force deficit with single (F_(1,9) = 0.02, p = 0.88, pƞ² = 0.003) or repeated (F_(1,9) = 0.006, p = 0.93, pƞ² = 0.001) MVIC testing were observed. The H-reflex did not change after the fatigue (F_(1,7) = 0.51; p = 0.49; pƞ² = 0.06) or repeated MVICs (F_(1,8) = 0.27; p = 0.61; pƞ² = 0.03). There were also no crossover effects of fatigue on the V-wave with single (F_(1,8) = 3.71, p = 0.09, pƞ² = 0.31) or repeated MVICs (F_(1,6) = 1.45, p = 0.27, pƞ² = 0.19). Crossover fatigue was not evident with the plantar flexors nor any significant changes in H-reflex and V-waves in the soleus muscle. This finding suggests that crossover fatigue may not necessarily occur in slow-twitch predominant muscle groups. Key points

• There were no significant crossover impairments in muscle endurance suggesting that when unilaterally training the plantar flexors, crossover decrements may not be an issue.
• Unilaterally fatiguing the plantar flexors induces only a trivial chance of experiencing single or discrete contraction force or strength decrements in the contralateral limb.

Key words: Non-local muscle fatigue, soleus, fatigue, Hoffman reflex, V-wave