Ventricular rate smoothing for atrial fibrillation: a quantitative comparison study.

AIMS: To quantitatively compare the ventricular rate-smoothing (VRS) effects of different ventricular pacing (VP) protocols for atrial fibrillation (AF). METHODS AND RESULTS: Using a recently developed open-source model that can simulate the ventricular response in AF and VP, the performance of fixed-rate pacing and four previously published VRS algorithms were assessed by the mean RR (mRR), the root mean square of successive RR differences (RMSSD), the percentage of ventricular senses (VS%), and the percentage of short RR intervals (sRR%). All pacing protocols cause rate-dependent reduction of RMSSD, VS%, and sRR% with or without shortening of mRR compared to spontaneous AF. Fixed-rate pacing was more sensitive to the intrinsic rate than the VRS algorithms. The performance was generally comparable between different VRS algorithms, although higher mRR and VS% can be achieved at the expense of larger RMSSD and sRR%. CONCLUSION: The effect of VP on ventricular rhythm in AF depends on both intrinsic rate and the aggressiveness of the pacing protocol. Adequate rate control is necessary for effective operation of the VRS algorithm. Choosing VRS algorithm should balance between the beneficial effects of rate regularization and the negative effects of increasing heart rate and percentage of VP.     

Degradable injectable bone cement in maxillofacial surgery: indications and clinical experience in 27 patients.

BACKGROUND: A carbonated apatite cement (NORIAN SRS) was used as a bone mineral substitute for the calvaria or viscerocranium in 27 patients. It has the consistency of a paste and hardens at physiologic pH and body temperature due to dahllite crystallization, which has the stoichiometric formula Ca(8.8)(HPO(4))(0.7)(PO(4))(4.5)(CO(3))(0.7)(OH)(1.3). MATERIAL AND METHODS: The cement was used for posttraumatic bone defects in the orbital, periorbital or malar regions (nine patients), posttraumatic deformities of the frontal bone (six patients), tumour-dependent bony defects of the calvaria (two patients) and posttraumatic or cystic defects of the mandible (five patients). In another five patients, the material was used to augment the atrophic anterior mandible in combination with the insertion of dental implants. Follow-up varied between 6 and 40 months (mean: 29 months). RESULTS: There was no inflammatory reaction surrounding the implanted material. There was no sign of infection in any of the patients and only one case of partial wound dehiscence with superficially exposed material. The defect fillings and augmentations were successful in all patients. None of the 19 dental implants which were inserted in combination with the material showed any sign of infection or loosening. Also, there was no loosening of the implants after loading (mean follow-up: 15 months). From the check-up radiographs, the material could be seen as a dense, radio-opaque structure. There were no material fractures or dislocations. Radiologically, the material seemed to be completely replaced by bony tissue after 30 months. CONCLUSION: Our 5-year clinical experience suggests that the material is a suitable bone mineral substitute for cranio-maxillofacial surgery especially for moderate-sized defects of the calvaria and forehead bone. It has advantages over preformed, solid bone substitute materials, and, due to its initial plasticity and eventual great compressive strength, it can also stabilize dental endosseous implants in the atrophic mandible.     

Entacapone improves complex movement performance in patients with Parkinson's disease.

BACKGROUND: A possible strategy to prolong plasma metabolism of Levodopa/Carbidopa (LD/CD) is Entacapone addition (EN), which improves impaired motor behaviour in patients with Parkinson's disease (PD). AIMS OF THE STUDY: Objectives were to evaluate the clinical response to an increased dopaminergic substitution with EN by clinical rating and assessment of complex motions and to investigate the change of movement in PD patients during repeat drug administration during an eight hour interval. METHODS: We used peg insertion with a computer based device and clinical rating for assessment of motor function in 20 treated PD patients. They received LD/CD and then the same LD/CD dosage plus EN in a standardised, open label fashion. RESULTS: Motor scores and performance of the instrumental task were significantly better and the fluctuation of movement was less intense during the LD/CD/EN condition according to the motor test outcomes. CONCLUSION: EN supplementation improves motor symptoms and provides a more continuous movement behaviour in PD patients.     

A randomized clinical trial with a 0.6% amino acid/ 1.4% glycerol peritoneal dialysis solution.

BACKGROUND: Glucose is an accepted osmotic agent for peritoneal dialysis (PD) although it has several drawbacks. Some of these drawbacks have been addressed by the introduction of solutions with low glucose degradation products and physiological pH in dual-chambered bags. Despite this achievement, there is a need for alternative osmotic agents.This randomized clinical trial analyzes 3-month's clinical experience with a mixture of 0.6% amino acids and 1.4% glycerol. METHODS: The study was performed at the renal units of the University Hospitals Ghent, Belgium, and Utrecht, The Netherlands. Stable PD patients were randomized for either protocol A (test solution, n = 5) or protocol B (control regimen, n = 5). In both protocols, there was a run-in phase of 1 month with a dialysis regimen of 2 x 2 L 2.27% glucose solution (Dianeal; Baxter, Nivelles, Belgium), 1 x 2 L Extraneal (Baxter), and 1 x 2 L glucose solution (Dianeal). After this month-long run-in period, patients in group A received during 3 months 2 x 2 L amino acid/glycerol solution, 1 x 2 L Extraneal, and at least 1 x 2 L of a classic glucose solution. RESULTS: Glucose absorption decreased in the test group during the test phase (from 84.2 +/- 8.7 to 11.7 +/- 11.6 g/24 hours, p = 0.001). Dialysate levels of cancer antigen 125 (CA125) increased in the test group, from 17.5 +/- 11.0 to 32.4 +/- 4.6 units/L (p = 0.04), whereas, in the control group, the levels remained stable (15.5 +/- 8.7 and 14.9 +/- 9.8 units/L respectively, p = 0.4).There were no differences in serum urea, serum bicarbonate, serum osmolarity, serum albumin, or parameters related to skin-fold thickness or serum glycerol levels between control and test solutions. No differences were observed in obtained ultrafiltration after a 4-hour dwell with 2.27% glucose or the test solution, both measured at week 4 of the run-in period and week 12 of the test period. CONCLUSION: This study demonstrated that the use of a new 0.6% amino acid/1.4% glycerol-containing dialysis solution is safe and well tolerated. Glucose load was reduced significantly and dialysate CA125 levels improved significantly. Ultrafiltration was comparable with that of a 2.27% glucose solution. All these factors, in combination with the potential nutritional benefits, can contribute to a beneficial impact on the success of the PD technique. Further long-term studies in larger patient groups are warranted to explore the potential of this promising new solution.     

RF refocused echoes of J-coupled spin systems: effects on RARE-based spectroscopic imaging.

A numerical simulation tool was developed to calculate the echo amplitudes of J-coupled resonances within a series of radiofrequency (RF) refocused echoes. The signal modulation due to J-coupling in rapid acquisition with relaxation enhancement (RARE) is suppressed only when the inverse of the pulse interval (tau) is large compared to both the chemical shift (CS) difference (Deltadelta) of the coupled spins and the coupling constant. In contrast, the echo amplitudes in ultrafast low-flip-angle RARE (U-FLARE) oscillate around a quasi-steady-state value that is greater than zero (neglecting relaxation and diffusion) even when Deltadelta > 1/tau. The flip-angle distribution over the measured slice caused by the use of Gaussian-shape slice-selective refocusing pulses further reduces the echo oscillations. When the pulse interval falls short of the fast pulse rate regime, spectroscopic U-FLARE provides an improved spatial impulse response in the phase-encoding (PE) direction compared to spectroscopic RARE.     

Cortisol moderates the relationship between testosterone and aggression in delinquent male adolescents.

BACKGROUND: In animals, strong evidence exists for an association between testosterone and aggression. In humans, and particularly in children and adolescents, findings have been less consistent. Previous research has suggested that this may partly be due to moderating effects of other factors, e.g., hormones. This study aims to investigate the moderating effect of cortisol on the relationship between testosterone and subtypes of aggression in delinquent male adolescents. METHODS: Participants were 103 boys (mean age 13.7) referred to a delinquency diversion program. Testosterone and cortisol levels were determined from saliva samples collected during resting conditions and related to self-report scores on overt and covert aggression. RESULTS: Linear regression analyses revealed a significant interaction between cortisol and testosterone in relation to overt aggression, with a significant positive relationship between testosterone and overt aggression in subjects with low cortisol levels but not in subjects with high cortisol levels. Using the same model for covert aggression, no significant effects of testosterone, cortisol, or testosterone x cortisol interaction were found. CONCLUSIONS: These results indicate a moderating effect of cortisol on the relationship between testosterone and overt aggression in delinquent male adolescents. Implications and directions for future research are discussed.     

18F-FDG PET for mediastinal staging of lung cancer: which SUV threshold makes sense?

(18)F-FDG PET is the most accurate noninvasive modality for staging mediastinal lymph nodes in lung cancer. Besides using visual image interpretation, some institutions use standardized uptake value (SUV) measurements in lymph nodes. Mostly, an SUV of 2.5 is used as the cutoff, but this choice was never deduced from respective studies. Receiver operating characteristic (ROC) analyses demonstrated that SUV thresholds of more than 4 resulted in the highest accuracy. But these high cutoffs imply high false-negative rates (FNRs). The aim of our evaluation was to determine an optimal SUV threshold and to compare its diagnostic performance with the results of visual interpretation. METHODS: This retrospective study included 95 patients with suspected lung cancer who underwent mediastinoscopy/mediastinal lymphadenectomy after (18)F-FDG PET (90-150 min after 250 MBq of (18)F-FDG). Maximum SUV was measured in 371 lymph node regions biopsied afterward and visually interpreted using a 6-level score (- - - through + + +). Diagnostic performance was assessed by ROC analysis. FNR and false-positive rate (FPR), the sum of both error rates (FNR + FPR), and diagnostic accuracy were plotted against a hypothetical SUV threshold to determine the optimum SUV threshold. RESULTS: SUVs in metastatic lymph nodes were higher (mean +/- SD, 7.1 +/- 4.5; range, 1.4-26.9; n = 70) than in tumor-free lymph node stations (2.4 +/- 1.7; range, 0.6-14.9; n = 301; P < 0.01). Inflammatory lymph nodes exhibited slightly increased SUVs (2.7 +/- 2.0; range, 0.8-14.9; n = 146). The plot of error rates featured a minimum of the sum FNR + FPR for an SUV of 2.5. With increasing SUV threshold, the FPR decreased most prominently up to that value whereas a continuous rise of FNR was noticed. Highest diagnostic accuracy was achieved with an SUV of 4.5. The areas under the ROC curves demonstrated that visual interpretation tends to be more accurate than SUV quantification (visual, 0.930 +/- 0.022; SUV, 0.899 +/- 0.025; P = 0.241). Using an SUV of 2.5 as the threshold, the resulting sensitivity, specificity, and negative predictive value were 89%, 84%, and 96%, respectively. CONCLUSION: For mediastinal staging, the choice of an SUV of 2.5 as the threshold is justified because FNR + FPR is minimized. The resulting high negative predictive value of 96% allows the omission of mediastinoscopy in patients with negative mediastinal findings on (18)F-FDG PET images. For the experienced observer, visual analysis should be relied on primarily, with calculation of the SUV used, at most, as a secondary aid. For the less experienced observer, the SUV may be of greater value.     

When distraction is not distracting: a behavioral and ERP study on distraction in ADHD.

OBJECTIVE: Although an increased distractibility is one of the behavioral criteria of Attention Deficit Hyperactivity Disorder (ADHD), there is little empirical evidence that children with ADHD are in fact more distractible than their normal peers. METHODS: We recorded event-related potentials (ERPs) to distracting novel sounds (novels) and standard sounds, (standards) while children performed a visual two-choice reaction time task. Twenty-five children with ADHD were compared with eighteen normal controls (aged 8-12 years). RESULTS: Children with ADHD showed a larger early P3a (150-250 ms), both in response to the standard and in response to the novel. The late phase of the P3a had a larger amplitude in the ADHD group in the 250-300 ms window compared to the control group, which was only present in response to the novel. Interestingly, the novel reduced the errors of omission in the ADHD group to a greater extent than in the normal control group. CONCLUSIONS: Although children with ADHD show an increased orienting response to novels, this distracting information can enhance their performance temporarily, possibly by increasing their arousal to an optimal level, as indicated by the reduced omission rate. SIGNIFICANCE: These data indicate that distraction is not always distracting in children with ADHD and that distraction can also have beneficial effects.     

Retrograde flush following topical cooling is superior to preserve the non-heart-beating donor lung

Objective: The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. Formation of microthrombi after circulatory arrest, however, is a major concern for the development of reperfusion injury. We looked at the effect and the best route of pulmonary flush following topical cooling in NHBD. Methods: Non-heparinized pigs were sacrificed by ventricular fibrillation and divided into three groups (n = 6 per group). After 1 h of in situ warm ischaemia and 2.5 h of topical cooling, lungs in group I were retrieved unflushed (NF). In group II, lungs were explanted following an anterograde flush (AF) through the pulmonary artery with 50 ml/kg Perfadex^® (6 °C). Finally, in group III, lungs were retrieved after an identical but retrograde flush (RF) via the left atrium. Flush effluent was sampled at intervals to measure haemoglobin concentration. Performance of the left lung was assessed during 60 min in our ex vivo reperfusion model. Wet-to-dry weight ratio (W/D) of both lungs was calculated as an index of pulmonary oedema. IL-1ß and TNF- protein levels in bronchial lavage fluid from both lungs were compared between groups. Results: Haemoglobin concentration (g/dl) was higher in the first effluent in RF versus AF (3.4 ± 1.1 vs 0.6 ± 0.1; p < 0.05). Pulmonary vascular resistance (dynes × s × cm⁻⁵) was 975 ± 85 RF versus 1567 ± 98 AF and 1576 ± 88 NF at 60 min of reperfusion (p < 0.001). Oxygenation (mmHg) and compliance (ml/cmH₂O) were higher (491 ± 44 vs 472 ± 61 and 430 ± 33 NS, 22 ± 3 vs 19 ± 3 and 14 ± 1 NS, respectively) and plateau airway pressure (cmH₂O) was lower (11 ± 1 vs 13 ± 1 and 13 ± 1 NS) after RF versus AF and NF, respectively. No differences in cytokine levels or in W/D ratios were observed between groups after reperfusion. Histology demonstrated microthrombi more often present after AF and NF compared to RF. Conclusion: Retrograde flush of the lung following topical cooling in the NHBD results in a better washout of residual blood and microthrombi and subsequent reduced pulmonary vascular resistance upon reperfusion.     

Fixation instability and oculomotor abnormalities in Friedreich's ataxia

Eye movements were studied in 13 patients with Friedreich's ataxia and correlated with MRI findings to investigate whether oculomotor abnormalities can be traced to cerebellar disturbances in this disease. One of the most prominent eye signs was fixation instability (square-wave jerks, SWJ.). Besides SWJ the patients showed various combinations of cerebellar, vestibular and brain-stem oculomotor signs. Our patients did not comprise a homogeneous group with regard to their oculomotor findings. There was no correlation between the severity of any of the so-called cerebellar oculomotor disturbances and the number of SWJ. We tried to correlate the extent of oculomotor disturbances with floccular atrophy and atrophy of the dorsal vermis on MRI in seven of the patients. None of the oculomotor features (including SWJ) correlated with flocculus or dorsal vermis size. Furthermore, floccular and vermal measurements on MRI were normal. Accordingly, we think it unlikely that the oculomotor disturbances, including SWJ, are attributable to cerebellar pathology per se.