Cervical soft tissue imaging using a mobile CBCT scanner with a flat panel detector in comparison with corresponding CT and MRI data sets.

OBJECTIVE: The aim of this study was to evaluate soft tissue image quality of a mobile cone-beam computed tomography (CBCT) scanner with an integrated flat-panel detector. STUDY DESIGN: Eight fresh human cadavers were used in this study. For evaluation of soft tissue visualization, CBCT data sets and corresponding computed tomography (CT) and magnetic resonance imaging (MRI) data sets were acquired. Evaluation was performed with the help of 10 defined cervical anatomical structures. RESULTS: The statistical analysis of the scoring results of 3 examiners revealed the CBCT images to be of inferior quality regarding the visualization of most of the predefined structures. Visualization without a significant difference was found regarding the demarcation of the vertebral bodies and the pyramidal cartilages, the arteriosclerosis of the carotids (compared with CT), and the laryngeal skeleton (compared with MRI). Regarding arteriosclerosis of the carotids compared with MRI, CBCT proved to be superior. CONCLUSIONS: The integration of a flat-panel detector improves soft tissue visualization using a mobile CBCT scanner.     

Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.     

Adjuvant chemotherapy in completely resected non-small-cell lung cancer.

Surgery alone has long been the standard treatment for patients with operable non-small-cell lung cancer (NSCLC). However, despite complete resection, 5-year survival rates have been disappointing, with about 50% of patients eventually suffering relapse and death from disease. Randomized trials conducted in the 1980s hinted at a survival benefit for postoperative cisplatin-based regimens, but they were underpowered. A meta-analysis published in 1995 found a nonsignificant 13% reduction in the risk of death associated with cisplatin-based chemotherapy, with an increase of survival of 5% at 5 years. This led to renewed interest in adjuvant chemotherapy in resected NSCLC. Thousands of patients have been included in a new generation of randomized trials in the last 10 years. Most of these recent studies have now been reported and several have demonstrated a clear survival advantage for patients treated with platin-based adjuvant therapy. These results also suggest a greater benefit with modern two-drug regimens. In view of the most recent data, postoperative platin-based chemotherapy can now be considered the standard of care for completely resected NSCLC patients with good performance status.     

Generation of cell diversity and segmental pattern in the embryonic central nervous system of Drosophila.

Development of the central nervous system (CNS) involves the transformation of a two-dimensional epithelial sheet of uniform ectodermal cells, the neuroectoderm, into a highly complex three-dimensional structure consisting of a huge variety of different neural cell types. Characteristic numbers of each cell type become arranged in reproducible spatial patterns, which is a prerequisite for the establishment of specific functional contacts. The fruitfly Drosophila is a suitable model to approach the mechanisms controlling the generation of cell diversity and pattern in the developing CNS, as it allows linking of gene function to individually identifiable cells. This review addresses aspects of the formation and specification of neural stem cells (neuroblasts) in Drosophila in the light of recent studies on their segmental diversification.     

Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder.

The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly (P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.     

Does systemic inflammation trigger local exercise-induced oxidative stress in COPD?

Inflammatory abnormalities may be involved in the inadequate basal oxidant/antioxidant balance and local exercise-induced oxidative stress in chronic obstructive pulmonary disease (COPD) patients. The time course of oxidative stress and inflammation was investigated in 10 COPD patients and seven healthy subjects before and after local dynamic quadriceps endurance exercise at 40% of maximal strength. Venous samples were collected before, immediately after and up to 48 h after exercise. At rest, levels of an oxidant released by stimulated phagocytes, the superoxide anion, were significantly higher in patients, as were plasma levels of C-reactive protein, tumour necrosis factor-alpha and interleukin-6, inflammatory markers. An inverse relationship was found between baseline C-reactive protein levels and endurance time in patients. Six hours after exercise, superoxide anion release and levels of protein oxidation products, an index of oxidative stress, increased similarly in both groups, whereas thiobarbituric acid reactive substance levels, another index of oxidative stress, increased significantly only in patients. Plasma nonenzymatic antioxidant and inflammatory cytokine levels were unchanged by the exercise protocol. The increased baseline systemic inflammation in chronic obstructive pulmonary disease patients could be related to disturbed oxidant/antioxidant balance, and, together, these may have triggered the exercise-induced oxidative stress. The absence, however, of local exercise-induced systemic inflammation suggests that additional mechanisms explain local exercise-induced oxidative stress.     

Diagnosis of diffuse and localized arrhythmogenic right ventricular dysplasia by gated blood-pool SPECT.

This study aimed to assess the ability of global and local systolic parameters measured with gated blood-pool SPECT (GBPS) to diagnose and characterize the severity of diffuse or localized arrhythmogenic right ventricular dysplasia (ARVD). METHODS: Fifty-nine subjects with symptomatic ventricular arrhythmias were prospectively included in the study. With the International Society and Federation of Cardiology criteria for ARVD as a gold standard, these subjects were classified as subjects without ARVD (21 control subjects) and patients with localized ARVD (16 patients) or diffuse ARVD (22 patients). Right ventricular volumes, right ventricular ejection fractions (EF), the SD of local EF (sigma-EF), and the SD of the local times of end systole (sigma-TES) were computed from GBPS data and compared among the groups in the study population. RESULTS: sigma-EF did not differ between control subjects and patients with diffuse or localized ARVD. Right ventricular EF and volumes differed between patients with diffuse ARVD and control subjects, with similar areas under the receiver-operating-characteristic curves, but right ventricular EF and volumes failed to differentiate patients with localized ARVD. In contrast, sigma-TES differed between patients with diffuse or localized ARVD and control subjects. Regression analysis showed that the systolic parameter most strongly associated with the diagnosis of ARVD was sigma-TES. The probabilities of a randomly chosen patient in the diffuse ARVD group and of a randomly chosen patient in the localized ARVD group having sigma-TES values greater than that of a randomly chosen control subject were 98.5% and 96.7%, respectively. For the diagnosis of localized ARVD, a threshold of 80 ms for sigma-TES corresponded to sensitivity, specificity, and positive and negative predictive values of 100%, 81%, 80%, and 100%, respectively. CONCLUSION: With GBPS, both diffuse ARVD and localized ARVD can be accurately diagnosed by computing sigma-TES for all of the pixels on the surface of the right ventricle.     

Mechanical restitution curves: a possible load independent assessment of contractile function.

OBJECTIVE: The time constant of mechanical restitution (T((MRC))), proposed to reflect changes in calcium release and uptake, has been shown to increase in left ventricular (LV) failure, and might have a potential as an index of contractile function. However, in vivo studies of the effect on T((MRC)) of changing loading conditions in the normal and failing heart have not been reported. Consequently, in this study, we tested the hypothesis that the increase in T((MRC)) in vivo is independent of preload and afterload. METHODS: Left ventricular pressure-volume loops were assessed at baseline in eight open chest pigs using the combined pressure-volume conductance catheter technique during right atrial pacing at 120b/min. Mechanical restitution curves (MRC) were constructed during four different loading conditions in all eight animals: uninfluenced load, reduced preload (balloon catheter in v. cava inferior), increased afterload (balloon catheter in descending aorta), and increased preload combined with reduced afterload (aortocaval shunting). Acute LV failure was then induced by microembolization through the left main coronary artery, and the experimental protocol was repeated. Contractile response was defined as the maximal first derivative of pressure (dP/dt(max)), and T((MRC)) was calculated using a least square approximation algorithm. RESULTS: Hemodynamic data 30min after microembolization showed decreased mean arterial pressure (98+/-14-67+/-10mmHg, (mean+/-SD) P<0.0001) and dP/dt(max) (1482+/-193-1001+/-125mmHg/s, P=0.001). Stroke volume decreased from 30+/-5 to 20+/-5ml (P<0.0001) compared to baseline, and preload recruitable stroke work decreased from 52+/-7 to 31+/-10mmHg (P=0.002). T((MRC)) increased in all eight animals after induction of LV failure at all loading conditions. There was no difference between the different loading conditions at baseline, nor at LV heart failure, but T((MRC)) increased significantly after the induction of heart failure (ANOVA, two ways). CONCLUSIONS: We have shown that the left ventricular T((MRC)) increases after developed heart failure. The increase in T((MRC)) was independent on loading conditions and thus have a potential for a contractility index.     

Bone morphogenetic proteins: from their discoveries till their clinical applications

Since their discovery 40 years ago by Urist M., several studies have been done on the bone morphogenetic proteins (BMP). They belong to the superfamily of TGF β (Transforming Growth Factor) and are the only osteo-inductive growth factors known until now. They are nowadays up to 20. After the fixation of these molecules on their receptors, intracellular cell reactions occur, inducing bone formation by the activation of genes responsible for cartilaginous formation and osteogenesis. In experimental studies on animal species, BMP showed their efficiency on the recovery of bone defects, on the acceleration of fractures consolidation or spine arthrodesis fusion or on pseudarthrodesis treatment. To be efficient, BMP must be used at the proper dose and delivered locally for a sufficient period by a biocompatible and biodegradable matrix, whose tridimensional structure allows its invasion by new bone and vascular cells. According to these data, clinical trials have been conducted on the human. Only rhBMP-2 and rhBMP-7 uses are validated for definite clinical applications (vertebral fusion, tibial pseudarthrosis and open leg fracture) by the results of randomized multicentric studies. Other clinical applications have been reported in the literature but large-scale studies are still necessary to confirm their results. Even if the clinical results are sometimes spectacular, and if the use of BMP, currently reserved because of their cost, in difficult situations give rise to big hopes, many questions remain unsolved. These questions will probably be dealt with in the future: stability of the new bone formation, eventual long-term adverse effects.