Frequency and prognostic value of HLA antigens in osteosarcoma patients

A homogeneous group of 53 Caucasian subjects with high-grade osteosarcoma (OS) was typed for HLA-A and B locus antigens. Although no significant differences in the distribution of these antigens were found in comparison with 425 local controls, a trend towards an increase of HLA-B18 and decrease of HLA-B21 was observed. All the patients underwent amputation plus adjuvant chemotherapy and among the 29 patients with a follow-up longer than one year, 9 out of 10 subjects with HLA-A3 antigens developed metastases within a few months. None of the OS patients had the HLA-A3, B7 haplotype which is present in linkage-disequilibrium in the control population.     

The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA

To determine whether patients with a HLA-identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-to-treat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P = 0.01, RR 0.78, 95% confidence interval 0.63–0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P = 0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.     

Safety and Effectiveness of Transvenous Lead Extraction in Octogenarians

Transvenous Lead Extraction . Introduction: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians. Methods and Results: From January 2005 to January 2011, we reviewed data from consecutive patients ≥ 80 years referred to our institutions for transvenous lead extraction because of cardiac device infection or lead malfunction. Clinical characteristics, procedural features, and periprocedural major and minor complications were compared between octogenarians and younger patients. Out of 849 patients undergoing lead extraction in the participating institutions during the study period, 150 (18%) patients were octogenarians (mean age 84 years; range 80–96; 64% males). A significantly higher percentage of octogenarians presented with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs 6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P < 0.001). Complete lead extraction rates were similar in the 2 age groups (97% in octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death occurred in 2 (1.3%) patients ≥80 years and in 5 (0.72%) patients <80 years (P = 0.45 for comparison). No differences in terms of other periprocedural major and minor complications were found between the 2 age groups. Conclusion: Despite presenting with a significantly higher rate of comorbidities, transvenous lead extraction can be performed safely and successfully in octogenarians. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1103‐1108, October 2012)     

Digestion by pancreatic juice of a beta-casomorphin-containing fragment of buffalo beta-casein

Degradation by pig pancreatic juice of a beta-casomorphin-containing fragment (tryptic peptide corresponding to residues 49–68 of buffalo beta-casein) was investigated. The FAB/MS (fast atom bombardment mass spectrometry) technique was used to identify the fragments produced by the concerted action of pancreatic proteases. Pancreatic juice, under our experimental conditions, is not able to release beta-casomorphins or morphiceptin from the tryptic peptide sequence. Furthermore, the present report shows that the rapid hydrolysis of a peptide bond by a single protease can prevent the cleavage of peptide bonds by a different protease. Therefore the formation of some peptides in the gastrointestinal tract can depend on the protease ratio.     

Patterns of Atrioventricular Conduction During Postexercise Recovery in Patients with Atrial Fibrillation and Wolff-Parkinson-White Syndrome

The effects of the postexercise recovery phase on the functional anterograde conduction properties of the accessory pathway (AP) were evaluated. Twenty-nine patients with Wolff-Parkinson-White (WPW) syndrome were submitted to supine maximal bicycle exercise testing. In seven patients (group I), in whom sustained atrial fibrillation (AF) could be induced by transesophageal pacing (TP), mean ventricular rate (MVR), the shortest R-R interval (SRR) between preexcited beats, and the observed percentage of preexcited beats were evaluated at rest, after each step of exercise and 2 minutes after the end of exercise. In 22 patients (group II), in whom sustained AF could not be induced, decremental TP was performed to evaluate the shortest atrial cycle length (SCL) with 1:1 conduction over AP at rest, after each step of exercise, and 2 minutes after the end of exercise. In four patients in group I, the protocol was repealed with atropine injected during the last minute of exercise. In 12 patients (three from group I and nine from group II), catecholamine plasma levels were measured at rest, at peak exercise, and during recovery. MVR was 144 ± 20 beats/min at rest, 186 ± 21 beats/min at peak exercise (P < 0.001 vs rest), and 179 ± 21 beats/min during recovery (P < 0,001 vs rest; P < 0.05 vs peak exercise). SRR was 289 ± 73 msec at rest, 223 ± 25 msec at peak exercise (P < 0.05 vs rest), and 227 ± 29 msec during recovery. Preexcited beat percentage was 95.4 ± 12 at rest, 35.2 ± 24.2 at peak exercise (P < 0.001 vs rest), and 85.1 ± 22.5 during recovery fP < 0.01 vs peak exercise and n.s. vs rest). In patients in whom atropine was injected MVR was 139 ± 17 beafs/min at rest, 184 ± 19 beats/min at peak exercise (P < 0.05 vs rest), and 172 ± 16 beats/min during recovery (P < 0.05 vs peak exercise, P < 0.05 vs rest); SRR was 320 ± 71 msec at rest, 225 ± 25 msec at peak exercise, and 232 ± 3 inset; during recovery; preexcited beat percentage was 99 ± 1 at rest, 26 ± 18 at peak exercise (P < 0.01 vs rest), and 28 ± 20 during recovery (NS vs peak exercise, P < 0.01 vsrest). In group II. mean sinus rate was 84 ± 12 beats/min at rest, 151 ± 15 beats/min at peak exercise, and 117 ± 21 beats/min 2 minutes after the end of exercise; mean SCL was 328 ± 75 msec at rest, 273 ± 76 msec at peak exercise (P < 0.0001 vs rest), and 280 ± 79 msec during recovery (P < 0.0001 vs rest and NS vs peak exercise). Mean epinephrineand norepinephrine plasma levels (12 patients from groups I and II) were; 4 7.9 ± 76.6 and 355.5 ± 185.1 pg/mL at rest; 193.0 ± 88.0 and 823.9 ± 390.3 pg/mL at peak exercise (P < 0.0001 vsrest); 148.5 ± 94.5 and 672.7 ± 272.3 during recovery (P < 0.001 vs rest; P < 0.01 vs peak exercise). Thus, during early recovery versus peak exercise: SCL and SRR are still lower and confirm the persistence of increased AP conductivity; in patients with atrial fibrillation preexcited beat percentage is markedly enhanced while the duration of preexcited complexes is increased and MVR is still high. The poslexercise recovery phase in patients with WPWand atrial fibrillation determines a higher ventricular response rate with major preexcitation than does rest and peak exercise. The fact that atropine prevents increases in preexcited beats percentage demonstrates that the underlying electrophysiological basis is a discordance of autonomic effects on the conduction properties of the two afrioventricular pathways.     

Conformational preferences and self-association modes of two diastereomeric statine derivatives

The conformational preferences and self-association modes of the two diastereomeric N-acetyl, methylamides of 3-hydroxy, 4-amino, 6-methylheptanoic acid (statine) with (R, S) and (S, S) configurations at the 3-hydroxy and 4-amino carbons, respectively, have been determined in solution as well as in the solid state by infrared absorption, ¹H nuclear magnetic resonance, and X-ray diffraction. Conformational energy computations have also been performed in parallel. In the crystal state, the change in chirality of the hydroxyl group induces different intermolecular H-bonding schemes in the (R, S) isomer compared to the two structurally distinct molecules in the asymmetric unit of the (S, S) isomer. Different propensities to self-aggregate are seen in solvents of low polarity. In solvents of high polarity, however, the molecules of both isomers are largely solvated, while still keeping some local conformational restriction. Conformational energy computations indicate that in vacuo the two diastereomers exhibit different flexibility, and a preferred conformation with a different type of intramolecular H-bond.     

Unexpected Discharge from an Implanted Automatic Defibrillator

The occurrence of inappropriate discharge from an implanted cardioverter-defibrillator is reported. The device was triggered by an episode of induced nonsustained ventricular tachycardia, and the shock was delivered 10 sec after spontaneous termination of the arrhythmia.
This observation demonstrates that unexpected discharges from an implanted cardiaverter/defibrillator can occur while the patient is asymptomatic. In order to avoid such an adverse effect, improvement of the detection system of the device is advisable.