Evaluation of Long-Term Outcomes, Cytogenetic and Molecular Responses with Imatinib Mesylate in Early and Late Chronic-Phase Chronic Myeloid Leukemia: A Report from a Single Institute

Here we compare the management and survival outcomes of chronic myeloid leukemia (CML) patients who had early or late imatinib mesylate (IM) therapy. The cytogenetic and molecular responses of 189 CML patients were analyzed. Of this group, 121 patients were classified as the early chronic phase (ECP) group and started IM within 12 months of diagnosis. The other 68 patients were classified as the late chronic phase (LCP) group who had been treated with interferon (IFN)-alpha-2 and crossed over to IM more than 12 months after diagnosis. The overall rates of complete cytogenetic response (CCyR) and major molecular response (MMR) at last follow-up were 83.6 and 78.1% in the ECP and LCP groups, respectively. The CCyR rates were 89.3 (for ECP patients) versus 73.5% (for LCP patients; p < 0.0001). At last follow-up, 82.4% ECP and 64.2% LCP patients had achieved an MMR (p < 0.0001). No significant differences were noted between the two groups with regard to survival outcomes. Our experience reveals that IM is an effective rescue therapy in most CML LCP patients who are intolerant or in whom IFN-alpha therapy fails. Such therapeutic options should be considered in LCP patients, particularly in countries where IM may not be available.     

Electrical impedance tomography to evaluate air distribution prior to extubation in very-low-birth-weight infants: a feasibility study

OBJECTIVES:

Nasal continuous positive airway pressure is used as a standard of care after extubation in very-low-birth-weight infants. A pressure of 5 cmH₂O is usually applied regardless of individual differences in lung compliance. Current methods for evaluation of lung compliance and air distribution in the lungs are thus imprecise for preterm infants. This study used electrical impedance tomography to determine the feasibility of evaluating the positive end-expiratory pressure level associated with a more homogeneous air distribution within the lungs before extubation.

METHODS:

Ventilation homogeneity was defined by electrical impedance tomography as the ratio of ventilation between dependent and non-dependent lung areas. The best ventilation homogeneity was achieved when this ratio was equal to 1. Just before extubation, decremental expiratory pressure levels were applied (8, 7, 6 and 5 cmH₂0; 3 minutes each step), and the pressure that determined the best ventilation homogeneity was defined as the best positive end-expiratory pressure.

RESULTS:

The best positive end-expiratory pressure value was 6.3±1.1 cmH₂0, and the mean continuous positive airway pressure applied after extubation was 5.2±0.4 cmH₂0 (p = 0.002). The extubation failure rate was 21.4%. X-Ray and blood gases after extubation were also checked.

CONCLUSION:

This study demonstrates that electrical impedance tomography can be safely and successfully used in patients ready for extubation to suggest the best ventilation homogeneity, which is influenced by the level of expiratory pressure applied. In this feasibility study, the best lung compliance was found with pressure levels higher than the continuous positive airway pressure levels that are usually applied for routine extubation.     

Anti-Leishmania infantum IgG Antibody Avidity in Visceral Leishmaniasis

IgG avidity tests are used to discriminate acute from chronic infections. There are few reports on the IgG avidity profile of patients with visceral leishmaniasis (VL). This study investigated the anti-Leishmania IgG avidity in patients with classic VL (n = 10), patients showing clinical cure after treatment (n = 18), and asymptomatic subjects with at least one positive Leishmania test (n = 20). All subjects were from areas in Brazil where VL is endemic. Serum samples were collected from each subject on two different occasions. IgG avidity was evaluated by Western blotting. The proportion of high-avidity antibodies was higher in all samples from patients with classic VL. In contrast, low-avidity antibodies predominated in subjects with a history of VL, including 13 cases (72.2%) in the first assessment and 14 (77.8%) in the second. Fifteen (75%) of the asymptomatic subjects presented a predominance of low-avidity antibodies in the first assessment, and the frequency of high-avidity antibodies increased over time in seven subjects (35%) of this group. Antibodies against the 14- and/or 16-kDa antigen fraction were detected in the first assessment in all patients with classic VL, in 10 (55.5%) treated patients, and in 10 (50%) asymptomatic subjects. These were high-avidity antibodies in most cases. In the asymptomatic group, an increase in IgG avidity against the 14- and/or 16-kDa antigen fraction was observed in three cases (15%). The results indicate distinct responses in infected and asymptomatic subjects, probably associated with the length of time after infection. In this respect, IgG avidity tests represent a new approach to better characterize asymptomatic VL.     

Aerobic exercise training delays cardiac dysfunction and improves autonomic control of circulation in diabetic rats undergoing myocardial infarction

BackgroundExercise training (ET) has been used as a nonpharmacological strategy for treatment of diabetes and myocardial infarction (MI) separately. We evaluated the effects ET on functional and molecular left ventricular (LV) parameters as well as on autonomic function and mortality in diabetics after MI.Methods and ResultsMale Wistar rats were divided into control (C), sedentary-diabetic infarcted (SDI), and trained-diabetic infarcted (TDI) groups. MI was induced after 15 days of streptozotocin-diabetes induction. Seven days after MI, the trained group underwent ET protocol (90 days, 50-70% maximal oxygen consumption-VO₂max). LV function was evaluated noninvasively and invasively; baroreflex sensitivity, pulse interval variability, cardiac output, tissue blood flows, VEGF mRNA and protein, HIF1-α mRNA, and Ca²⁺ handling proteins were measured. MI area was reduced in TDI (21 ± 4%) compared with SDI (38 ± 4%). ET induced improvement in cardiac function, hemodynamics, and tissue blood flows. These changes were probable consequences of a better expression of Ca²⁺ handling proteins, increased VEGF mRNA and protein expression as well as improvement in autonomic function, that resulted in reduction of mortality in TDI (33%) compared with SDI (68%) animals.ConclusionsET reduced cardiac and peripheral dysfunction and preserved autonomic control in diabetic infarcted rats. Consequently, these changes resulted in improved VO₂max and survival after MI.     

Reactive Tonsillar Enlargement Showing Strong 18F-Fdg Uptake During the Follow-Up of Follicular Lymphoma

The ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has become a standard procedure for the diagnosis, staging, and restaging in lymphoma patients. However, a relative high rate of false-positive results has been reported. We report a case of a 40-year-old man with a previous history of a nodal follicular lymphoma, stage IVA, treated with R-CHOP, which showed strong ¹⁸F-FDG uptake in the Waldeyer’s tonsillar ring during his follow-up, being considered highly suspicious of relapsed lymphoma. A surgical removal of the palatine tonsils and adenoids was performed, which showed reactive follicular hyperplasia. Furthermore, bone marrow biopsy revealed absence of neoplasia. The patient is still in follow-up with no signs of recurrent lymphoma. This case illustrates that, despite the high sensitivity for the detection of recurrent lymphoma, ¹⁸F-FDG uptake should be interpreted with great caution and confirmatory studies should be performed before any therapy.     

Laser irradiation did not increase the proliferation or the differentiation of stem cells from normal and inflamed dental pulp

ObjectiveLow-level laser therapy (LLLT) has been reported to be responsible for promoting photostimulatory and photobiomodulatory effects in vivo and in vitro, stimulating cell growth, increasing cell metabolism, improving cell regeneration and invoking an anti-inflammatory response. This study was performed in order to investigate whether low-level laser therapy could increase the proliferation and differentiation potentials of hDPSC isolated from healthy dental pulps and from inflamed pulps.DesignHuman dental pulp stem cells (hDPSC) were isolated from normal and inflamed dental pulps from different patients. STRO-1-positive cells were isolated and irradiated with a red low-level laser (660 nm) in four different energy fluences (0.05, 0.30, 7 and 42 J/cm²); the authors hypothesized that the first three fluences would promote biostimulatory effects, whereas the highest dose would induce antiproliferative effects. The two lower fluences were produced by irradiating the two higher fluences through a dentine disc, which was used to simulate a clinical condition. The proliferation and the cell odonto-osteogenic differentiation competence were compared.ResultsNo statistically significant differences were observed between the proliferation rates and the relative productions of mineralized nodules compared to the respective controls, either for hDPSC from normal or inflamed dental pulps.ConclusionsThe irradiation with low-level InGaAlP red low-level laser (660 nm) in four different energy fluences (0.05, 0.30, 7 and 42 J/cm²) potentiated neither proliferation nor odonto-osteogenic differentiation of hDPSC isolated from patients with normal and inflamed pulps.