PML-RARα kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukaemia treated with ATRA and ATO or ATRA and chemotherapy.

The APL0406 study showed that arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are not inferior to standard ATRA and chemotherapy (CHT) in newly diagnosed, low-intermediaterisk acute promyelocytic leukaemia (APL). We analysed the kinetics of promyelocytic leukaemia-retinoic acid receptor-α (PML-RARα) transcripts by real-time quantitative PCR (RQ-PCR) in bone marrow samples from 184 patients and assessed the prognostic impact of fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) in 159 patients enrolled in this trial in Italy. After induction therapy, the reduction of PML-RARα transcripts was significantly greater in patients receiving ATRA-CHT as compared with those treated with ATRA-ATO (3.4 vs 2.9 logs; P=0.0182). Conversely, at the end of consolidation, a greater log reduction of PML-RARα transcripts was detected in the ATRA-ATO as compared with the ATRA-CHT group (6.3 vs 5.3 logs; P=0.0024). FLT3-ITD mutations had no significant impact on either event-free survival (EFS) or cumulative incidence of relapse in patients receiving ATRA-ATO, whereas a trend for inferior EFS was observed in FLT3-ITD-positive patients receiving ATRA-CHT. Our study shows at the molecular level that ATRA-ATO exerts at least equal and probably superior antileukaemic efficacy compared with ATRA-CHT in low-intermediaterisk APL. The data also suggest that ATRA-ATO may abrogate the negative prognostic impact of FLT3-ITD.

Partial deletions of long arm of chromosome 6: biologic and clinical implications in adult acute lymphoblastic leukemia.

Within 285 adult acute lymphoblastic leukemias (ALL) included in the multicenter GIMEMA 0496 trial and prospectively studied by conventional cytogenetics, 18 cases (6%) with long arm deletion of chromosome 6 (6q) were identified. These cases were divided into: (i) del(6q) only (n = 6); (ii) del(6q) plus other numerical and/or structural abnormalities (n = 8); (iii) del(6q) and other 'specific' translocations (n = 4). The biologic and clinical features of the patients carrying this anomaly, as well as their outcome, were compared with those of 267 patients without del(6q). A T cell phenotype was more frequently associated with del(6q) cases in general (P = 0.001) and particularly with cases presenting del(6q) as the isolated abnormality (P = 0.0027). No significant difference with respect to multidrug resistance (MDR)/P glycoprotein expression was observed between the two groups of patients (21% vs 28% of MDR-positive cases, respectively). A BCR-ABL fusion transcript was less frequently detected in cases with del(6q) (11%) compared with those without the anomaly (29%). p15 and p16 deletions were identified by Southern blot analysis in 21% of cases with del(6q) and in 26% of cases without del(6q). In this latter group, a T cell phenotype was less frequently associated with p15 and/or p16 deletion than in the group carrying del(6q) (36% vs 100% of cases, P = 0.011). Overall, patients with ALL and del(6q) had a high complete remission (CR) rate (83%); however, they had a lower 18 month event-free survival (31% vs 41%) and a higher relapse rate (70% vs 37%, P = 0.02) compared with patients without del(6q). To date, this is the largest series of adult ALL cases reported with del(6q) homogeneously treated, which have also been prospectively studied for MDR expression and for the detection of known fusion genes. This anomaly, as an isolated change, identifies a subset of cases with hyperleukocytosis (median WBC count 52 x 10(9)/l) and a strict correlation with a T cell phenotype. Overall, del(6q) seems to be associated with an unfavorable clinical outcome, although this finding will need to be confirmed by extended FISH analysis.

Photorefractive keratectomy to correct myopic or hyperopic astigmatism with a cross-cylinder ablation.

PURPOSE: To assess the efficacy and safety of a combined ablation of the steep and flat meridian to correct astigmatism with the excimer laser. METHODS: Twenty-two eyes with myopic, mixed, or hyperopic astigmatism (mean preoperative spherical equivalent refraction -4.30 +/- 4.70 D [range, -12.50 to +1.50 D] and mean preoperative cylinder magnitude -3.40 +/- 1.40 D [range, -1.50 to -6.00 D]) underwent PRK with the Nidek EC-5000 excimer laser. The surgical strategy involved ablating half the amount of the cylinder (in diopters) along steepest meridian, the other half in a subsequent step along the flattest meridian; thereafter, the spherical equivalent was corrected. RESULTS: Six months postoperatively, mean spherical equivalent refraction was -0.07 +/- 0.87 D and mean cylinder was -0.44 +/- 0.36 D. Mean spectacle-corrected visual acuity was 0.86 +/- 0.13 compared to 0.75 +/- 0.22 preoperatively. Mean corneal haze was 0.67 +/- 0.31. No patient lost 2 or more lines of spectacle-corrected visual acuity and there were no complaints about night halos or glare. CONCLUSIONS: Unlike other ablation strategies, the cross-cylinder method creates a smooth transition (low dioptric gradient) between the treated and untreated cornea. This is achieved by first treating the cylinder and making the corneal surface spherical and then ablating the spherical component of the refractive error.

Algorithm to correct hyperopic astigmatism with the Nidek EC-5000 excimer laser.

BACKGROUND: The efficacy of a new ablation algorithm for the correction of hyperopic astigmatism with the Nidek EC-5000 excimer laser was evaluated. METHODS: Twenty-five eyes with mean preoperative hyperopia of +3.76 +/- 1.70 D and a mean hyperopic cylinder of 2.20 +/- 0.80 D underwent photorefractive keratectomy (PRK) using a new algorithm with the Nidek EC-5000 excimer laser (software version 3.0). The new algorithm differed from previous algorithms in that less tissue was removed for the same amount of diopters, and there was less of a dioptric gradient between the optical zone and the transition zone. Mean preoperative spectacle-corrected visual acuity was 0.8 +/- 0.09. Minimum follow-up was 6 months. RESULTS: Mean postoperative spectacle corrected visual acuity (geometric mean) increased significantly to 0.89 +/- 0.1. The mean sphere decreased by 3.08 D and the mean cylinder by 1.60 D. CONCLUSION: Hyperopic PRK using the Nidek EC-5000 excimer laser with this new algorithm for hyperopic astigmatism appears to be safe and effective.

A method for examining surface and interface irregularities after photorefractive keratectomy and laser in situ keratomileusis: predictor of optical and functional outcomes.

PURPOSE: To develop a system for the examination of the ablated surface after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) and to correlate the surface regularity to the functional outcome. METHODS: A Nidek Eas-1000 Anterior Eye Segment Analysis System was used to examine the ablated surface or the interface regularity immediately after PRK and LASIK. Eighty eyes were evaluated and divided into three study groups; group 1; regularity (18 eyes), group 2; mild irregularity (32 eyes) group 3; severe irregularity (30 eyes). RESULTS: At 12 months postoperatively, group 1 (regularity) showed the best percentage of eyes with 0 haze (100%) and with a refraction +/- 1.00 D of plano (89%); group 2 (mild irregularity) 84% had 0 haze and 62% were +/- 1.00 D of plano; group 3 (severe irregularity) 27% had 0 haze and 47% were +/- 1.00 D of plano. CONCLUSION: The patients with no postoperative irregularity had a sharply lower incidence of haze and a better refractive outcome with respect to plano, confirming the influence of ablation regularity on the results and the importance of this analysis in clinical practice.

Superficial inflammatory and primary neoplastic lymphadenopathy: diagnostic accuracy of power-doppler sonography.

OBJECTIVE: To evaluate the sensitivity, specificity and diagnostic accuracy of a cut-off of the resistive index of 0.5 for the differentiation between inflammatory and neoplastic primary lymphadenopathies. SUBJECTS AND METHODS: We measured the resistive index of superficial enlarged lymph nodes in a total of 50 patients (29 males and 21 females; age range 12-72 years, mean age 41.6 year) using an ATL 5000 HDI. A resistive index greater than or equal to 0.5 indicated an inflammatory lymph node and a resistive index <0.5 was consistent with neoplastic primary lymphadenopathies. The gold standard was either surgical biopsy or lymph-node reduction seen with ultrasound examination after antibiotic therapy. RESULTS: The sensitivity of the resistive index for distinguishing inflammatory from neoplastic lymphadenopathy was 84.6%, the specificity 100% and the diagnostic accuracy 95.7% (P < 0.001, statistically significant). CONCLUSION: The results of this study indicate that power-Doppler using a resistive index cut-off of 0.5 was a valid technique for distinguishing between inflammatory and primary neoplastic lymph nodes in patients with superficial lymphadenopathies.

Perfluorocarbon liquids as postoperative short-term vitreous substitutes in complicated retinal detachment.

To avoid postoperative "compartmentalization" of the vitreous cavity, which can potentially accelerate the recurrence of proliferative vitreoretinopathy (PVR), 32 eyes of 32 selected patients with complicated retinal detachment were managed with lensectomy, vitrectomy, 5-day internal tamponade with perfluorocarbon liquids (PFCL) and postoperative supine positioning until PFCL removal. Intraoperatively, 19 eyes had grade C3 or greater PVR; 10 eyes exhibited ocular trauma and 6 displayed giant tears. All but 5 patients (PFCL/fluid exchange) underwent PFCL/silicone oil exchange 5 days after surgery. Anatomic attachment of the retina was achieved with one operation in 25 (78%) of the 32 eyes with a median follow-up of 8 months (mean 8.4 months). Of the 20 eyes that underwent silicone oil removal, none redetached. Nineteen eyes (61%) showed no or only mild reproliferation; a macular pucker developed in 50% of the 20 eyes successfully reattached after PFCL/silicone oil exchange and in none of the 5 eyes successfully reattached after PFCL/fluid exchange. Intraocular tolerance of PFCL for up to 5 days of internal tamponade appeared to be good as judged by static threshold perimetry in the two patients tested and by our functional outcomes, with 88% of the reattached eyes showing a final visual acuity of 5/200 or better.

Chronobiological aspects of bronchial tone.

The aim of the investigation was to demonstrate the existence of cyclic variations of bronchial tone, correlated with the increase of vagal tone during nocturnal hours and with the increase of adrenergic tone in the late morning and afternoon. Twenty-five healthy subjects were tested, utilizing forced expiration curve (V/V loop), Raw and SGaw. We did not detect a statistically significant rhythm for FVC, FEV1, PEF, because they are effort-dependent parameters. On the contrary, we demonstrated significant fluctuations for V max50, FEF25.75 (acrophase in the later morning and early afternoon), for Raw (acrophase in late evening) and for SGaw (Acrophase in antiphase with Raw); these parameters are effort-independent as well as direct and sensitive indexes of the tone of peripheral and central airways.

[Circadian rhythm of ventilatory parameters of intrinsic asthma in clinical remission]. / Ritmo circadiano dei parametri ventilatori nell'asma primitiva in remissione clinica.

In six subjects with intrinsic asthma in clinical remission, time-structure of ventilatory parameters has been evaluated in order to evaluate: 1) which indexes present statistically significant circadian fluctuations; 2) if phase-shifts occur in comparison with normal subjects. After a period of synchronization of 7 days (L/D: 07.30-23.00; meal timing at 08.00, 13.00 and 20.30) all subjects have been studied by spirometry, flow-volume loop and Raw determination 6 times in a 24-hr period at constant intervals of 4 hrs. The results have been evaluated by macroscopic and microscopic analysis statistical significant fluctuations have been shown in these functional indexes: MEF50, Raw, SRaw, SGaw, FRC and RV; no phase-shifts occurred in comparison with normal subjects. On the contrary a circadian rhythm has not been shown in FVC, FEV1, and PEF. Therefore only the effort-independent test should be used to study correctly the bronchial tone.