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.     

Dasatinib overrides imatinib resistance mediated by the F359I residue mutation in two patients with chronic myeloid leukemia

Despite the beneficial effects of imatinib mesylate, some patients may either not respond or respond suboptimally. Here, we report two chronic myelogenous leukemia patients; one had a suboptimal response according to European LeukemiaNet criteria (a major molecular response was not achieved after 18 months of standard-dose imatinib therapy) and the other had failure with a standard dose of imatinib. At the time of the suboptimal response in patient 1 and the failure in patient 2, we were able to detect the F359I mutation in the BCR-ABL tyrosine kinase domain using DNA sequencing in both patients. Therefore, it was decided to change the therapeutic regimen to dasatinib at a dose of 100 mg once daily in both patients. This change resulted in the achievement of complete cytogenetic remission in patient 1 after 4 months and a major molecular response within 2 and 3 months in both patients. Detection of the F359I mutation in our two cases likely explains the suboptimal response to imatinib in case 1 and the failure in case 2. This implies that in such cases dasatinib should be considered to effectively suppress the mutated clones.     

Swallowing in Patients with Parkinson’s Disease: A Surface Electromyography Study

Our goal was to study deglutition of Parkinson??s disease (PD) patients and normal controls (NC) using surface electromyography (sEMG). The study included 15 patients with idiopathic PD and 15 age-matched normal controls. Surface electromyography was collected over the suprahyoid muscle group. Conditions were the following: swallow at once 10 and 20?ml of water and 5 and 10?ml of yogurt of firm consistency, and freely drink 100?ml of water. During swallowing, durations of sEMG were significantly longer in PD patients than in normal controls but no significant differences of amplitudes were found. Eighty percent of the PD patients and 20?% of the NC needed more than one swallow to consume 20?ml of water, while 70?% of the PD patients and none of the NC needed more than one swallow to consume 5?ml of yogurt. PD patients took significantly more time and needed significantly more swallows to drink 100?ml of water than normal controls. We conclude that sEMG might be a simple and useful tool to study and monitor deglutition in PD patients.     

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.     

The Number of Bleaching Sessions Influences Pulp Tissue Damage in Rat Teeth

Introduction

Hydrogen peroxide tooth bleaching is claimed to cause alterations in dental tissue structures. This study investigated the influence of the number of bleaching sessions on pulp tissue in rats.

Methods

Male Wistar rats were studied in 5 groups (groups 1S–5S) of 10 each, which differed by the number (1–5) of bleaching sessions. In each session, the animals were anesthetized, and 35% hydrogen peroxide gel was applied to 3 upper right molars. Two days after the experimental period, the animals were killed, and their jaws were processed for light microscope evaluation. Pulp tissue reactions were scored as follows: 1, no or few inflammatory cells and no reaction; 2, <25 cells and a mild reaction; 3, between 25 and 125 cells and a moderate reaction; and 4, 125 or more cells and a severe reaction. Results from each experimental group were compared between groups and within groups to the corresponding unbleached upper left molars and analyzed for significant differences using the Kruskal-Wallis test (P < .05).

Results

All tissue sections showed significant bleaching-induced changes in the dental pulp. After 1 bleaching session, necrotic tissue in the pulp horns and underlying inflammatory changes were observed. The extent and intensity of these changes increased with the number of bleaching sessions. After 5 sessions, the changes included necrotic areas in the pulp tissue involving the second third of the radicular pulp and intense inflammation in the apical third.

Conclusions

The number of bleaching sessions directly influenced the extent of pulp damage.