The neuronal apoptotic death in global cerebral ischemia in gerbil: Important role for sodium channel modulator

Global ischemia was induced in gerbil by bilateral occlusion of the common carotid arteries for 5 min. Sodium ionophore monensin or sodium channel blocker tetrodotoxin (TTX) was administered at doses of 10 μg/kg, i.p., 30 min before ischemia induction; the dose was repeated after 22 hr. Subsequently, brain infarct occurred, determined at 24 hr after occlusion. Large, well‐demarcated infarcts were observed in both hemispheres, an important observation because it critically influences the interpretation of the data. Because nitric oxide (NO) production is thought to be related to ischemic neuronal damage, we examined increases in Ca²⁺ influx, which lead to the activation of nitric oxide synthase (NOS). Then we evaluated the contributions of neuronal NOS, endothelial NOS, and inducible NOS to NO production in brain cryosections. The cytosolic release of apoptogenic molecules like cytochrome c and p53 were confirmed after 24 hr of reflow. TUNEL (terminal deoxynucleotidyl transferase dUTP nick‐end labeling) labeling detected the apoptotic cells, which were confirmed in neuron‐rich cell populations. After 24 hr, all the ischemic changes were amplified by monensin and significantly attenuated by TTX treatment. Additionally, the nesting behavior and histological outcomes were examined after 7 day of reflow. The neuronal damage in the hippocampal area and significant decrease in nesting scores were observed with monensin treatment and reduced by TTX pretreatment after day 7 of reflow. To our knowledge, this report is the first to highlight the involvement of the voltage‐sensitive Na⁺ channel in possibly regulating in part NO system and apoptosis in a cytochrome c–dependent manner in global ischemia in the gerbil, and thus warrants further investigation. © 2008 Wiley‐Liss, Inc.     

Intrajejunal levodopa infusion in Parkinson's disease: A pilot multicenter study of effects on nonmotor symptoms and quality of life

Switching from oral medications to continuous infusion of levodopa/carbidopa gel reduces motor complications in advanced Parkinson's disease (PD), but effects on nonmotor symptoms (NMSs) are unknown. In this prospective open‐label observational study, we report the effects of intrajejunal levodopa/carbidopa gel infusion on NMS in PD based on standard assessments utilizing the nonmotor symptoms scale (NMSS) along with the unified Parkinson's disease rating scale (UPDRS 3 motor and 4 complications) and quality of life (QoL) using the Parkinson's disease questionnaire (PDQ‐8). Twenty‐two advanced PD patients (mean age 58.6 years, duration of disease 15.3 years) were followed for 6 months. A statistically significant beneficial effect was shown in six of the nine domains of the NMSS: cardiovascular, sleep/fatigue, attention/memory, gastrointestinal, urinary, and miscellaneous (including pain and dribbling) and for the total score of this scale (NMSST) paralleling improvement of motor symptoms (UPDRS 3 motor and 4 complications in “best on” state) and dyskinesias/motor fluctuations. In addition, significant improvements were found using the Parkinson's disease sleep scale (PDSS) and the PDQ‐8 (QoL). The improvement in PDQ‐8 scores correlated highly significantly with the changes in NMSST, whereas a moderately strong correlation was observed with UPDRS changes. This is the first demonstration that a levodopa‐based continuous dopaminergic stimulation is beneficial for NMS and health‐related quality of life in PD in addition to the reduction of motor fluctuations and dyskinesias. © 2009 Movement Disorder Society     

Use of Live Interactive Webcasting for an International Postgraduate Module in eHealth: Case Study Evaluation

Background

Producing “traditional” e-learning can be time consuming, and in a topic such as eHealth, it may have a short shelf-life. Students sometimes report feeling isolated and lacking in motivation. Synchronous methods can play an important part in any blended approach to learning.

Objective

The aim was to develop, deliver, and evaluate an international postgraduate module in eHealth using live interactive webcasting.

Methods

We developed a hybrid solution for live interactive webcasting using a scan converter, mixer, and digitizer, and video server to embed a presenter-controlled talking head or copy of the presenter’s computer screen (normally a PowerPoint slide) in a student chat room. We recruited 16 students from six countries and ran weekly 2.5-hour live sessions for 10 weeks. The content included the use of computers by patients, patient access to records, different forms of e-learning for patients and professionals, research methods in eHealth, geographic information systems, and telehealth. All sessions were recorded—presentations as video files and the student interaction as text files. Students were sent an email questionnaire of mostly open questions seeking their views of this form of learning. Responses were collated and anonymized by a colleague who was not part of the teaching team.

Results

Sessions were generally very interactive, with most students participating actively in breakout or full-class discussions. In a typical 2.5-hour session, students posted about 50 messages each. Two students did not complete all sessions; one withdrew from the pressure of work after session 6, and one from illness after session 7. Fourteen of the 16 responded to the feedback questionnaire. Most students (12/14) found the module useful or very useful, and all would recommend the module to others. All liked the method of delivery, in particular the interactivity, the variety of students, and the “closeness” of the group. Most (11/14) felt “connected” with the other students on the course. Many students (11/14) had previous experience with asynchronous e-learning, two as teachers; 12/14 students suggested advantages of synchronous methods, mostly associated with the interaction and feedback from teachers and peers.

Conclusions

This model of synchronous e-learning based on interactive live webcasting was a successful method of delivering an international postgraduate module. Students found it engaging over a 10-week course. Although this is a small study, given that synchronous methods such as interactive webcasting are a much easier transition for lecturers used to face-to-face teaching than are asynchronous methods, they should be considered as part of the blend of e-learning methods. Further research and development is needed on interfaces and methods that are robust and accessible, on the most appropriate blend of synchronous and asynchronous work for different student groups, and on learning outcomes and effectiveness.     

Lipid-independent pleiotropic effects of statins in the management of acute coronary coronary syndromes

Opinion statement Acute coronary syndromes involve a complex interplay between the vessel wall, inflammatory cells, and the coagulation cascade. Statins possess beneficial effects that are independent of low-density lipoprotein cholesterol lowering and that have favorable effects on inflammation, the endothelium, and the coagulation cascade. There is now accumulating evidence that these lipid-independent pleiotropic effects are clinically relevant in the management of acute coronary syndromes.     

The role of psychosocial factors in predicting the onset of chronic widespread pain: results from a prospective population-based study

OBJECTIVE: Chronic widespread pain (CWP) is strongly associated with psychosocial distress both in a clinical setting and in the community. The aim of this study was to determine the contribution of measures of psychosocial distress, health-seeking behaviour, sleep problems and traumatic life events to the development of new cases of CWP in the community. METHODS: In a population-based prospective study, 3171 adults aged 25-65 yrs free of CWP were followed-up 15 months later to identify those with new CWP. Baseline data were available on their scores from a number of psychological scales including Illness Attitude Scales (IAS), Somatic Symptom Checklist (SSC), Hospital Anxiety & Depression Scale, Sleep Problems Scale, and Life Events Inventory. RESULTS: 324 subjects [10%, 95% confidence interval (CI) 9.2, 11.3] developed new CWP at follow-up. After adjustment for age and sex, three factors independently predicted the development of CWP: scoring three or more on the SSC [odds ratio (OR) 1.8, 95% CI 1.1, 3.1], scoring eight or more on the Illness Behaviour subscale of the IAS (OR 3.3, 95% CI 2.3, 4.8), and nine or more on the Sleep Problem Scale (OR 2.7, 95% CI 1.6, 3.2). Subjects exposed to all three factors were at 12 times the odds of new CWP than those with low scores on all scales. CONCLUSION: Subjects are at substantial increased odds of developing CWP if they display features of somatization, health-seeking behaviour and poor sleep. Psychosocial distress has a strong aetiological influence on CWP.     

Initial experience with a novel remote-guided magnetic catheter navigation system for left ventricular scar mapping and ablation in a porcine model of healed myocardial infarction

Objective: This study examined the feasibility of using a remote magnetic catheter navigation system (MNS) in concert with an EAM system to perform detailed left ventricular scar mapping and ablation in a porcine model of healed myocardial infarction.
Background : Substrate-based catheter ablation of ventricular tachycardia (VT) involves detailed electroanatomical mapping (EAM) of the ventricles. While a safe and effective procedure, VT ablation is nonetheless uncommonly performed, due in part to the technical challenges related to ventricular mapping.
Methods: Using a prototype EAM system (CARTO-RMT), seven chronically infarcted swine were mapped using either: (i) a standard manually manipulated catheter or (ii) a magnetic remotely manipulated (Niobe) catheter. A total of 191 ± 54 and 221 ± 64 points were acquired to map the chamber either manually or remotely, respectively.
Results: Procedure times were longer remotely (94 ± 22 vs. 59 ± 19 minute, P = 0.004; and 27 ± 8 vs. 18 ± 3 sec/point, P = 0.04), but this became less apparent with increased operator experience. However, the fluoroscopy time was significantly shorter with remote mapping (56 ± 56 vs. 244 ± 67 sec/map, P = 0.03). The calculated scar size was comparable between the two methods (16.3 ± 4.9 vs. 16.4 ± 4.8 cm², P = 0.37). Pathologic examination confirmed that the MNS was able to precisely deliver radiofrequency lesions to the scar borders. Using the MNS, the error to reach an evenly distributed set of endocardial targets was 6.6 ± 3.6 mm and 4.6 ± 2.0 mm, using transseptal and retrograde approaches, respectively.
Conclusions: Ventricular mapping using this remote navigation paradigm is technically possible and requires minimal fluoroscopy exposure, potentially facilitating ventricular substrate mapping and ablation.     

Current results of balloon aortic valvuloplasty in high-risk patients

In this report, we describe our experience with a contemporary series of patients with severe aortic stenosis (AS) undergoing balloon aortic valvuloplasty (BAV) who were not deemed to be surgical candidates. Demographic, hemodynamic and procedural data, operative risk (EuroSCORE) and long-term follow up were collected. Eighty consecutive patients with severe symptomatic AS underwent 104 BAV procedures as a single center and were followed for a mean of 3+/-2 years. Thirteen patients underwent 2 BAV procedures, 2 patients underwent 3 BAV procedures and 1 patient underwent 5 BAV procedures. Mean age was 81+/-10 years, and 23% were >90 years of age. Cardiogenic shock was present in 20% and the ejection fraction was <30% in 38% of the patients. The mean EuroSCORE was 16+/-5, and 98% had a high-risk EuroSCORE. There were no procedural deaths and 9 (9%) total vascular complications. In-hospital, 1-, 2- and 3-year mortality rates were 6%, 44%, 62% and 71%, respectively. Seventeen patients (21%) underwent repeat BAV procedures and had long-term mortality similar to those undergoing a single BAV procedure. Contemporary BAV has acceptable short- and long-term results and can effectively be used for patients deemed unsuitable surgical candidates and those at highest operative risk, such as patients with cardiogenic shock.     

Insulin therapy in type 2 diabetes patients failing oral agents: cost-effectiveness of biphasic insulin aspart 70/30 vs. insulin glargine in the US

OBJECTIVES: To project the long-term clinical and economic outcomes of treatment with biphasic insulin aspart 30 (BIAsp 70/30, 30% soluble and 70% protaminated insulin aspart) vs. insulin glargine in insulin-na?ve type 2 diabetes patients failing to achieve glycemic control with oral antidiabetic agents alone (OADs). METHODS: Baseline patient characteristics and treatment effect data from the recent 'INITIATE' clinical trial served as input to a peer-reviewed, validated Markov/Monte-Carlo simulation model. INITIATE demonstrated improvements in HbA1c favouring BIAsp 70/30 vs. glargine (-0.43%; p < 0.005) and greater efficacy in reaching glycaemic targets among patients poorly controlled on OAD therapy. Effects on life expectancy (LE), quality-adjusted life expectancy (QALE), cumulative incidence of diabetes-related complications and direct medical costs (2004 USD) were projected over 35 years. Clinical outcomes and costs were discounted at a rate of 3.0% per annum. Sensitivity analyses were performed. RESULTS: Improvements in glycaemic control were projected to lead to gains in LE (0.19 +/- 0.24 years) and QALE (0.19 +/- 0.17 years) favouring BIAsp 70/30 vs. glargine. Treatment with BIAsp 70/30 was also associated with reductions in the cumulative incidences of diabetes-related complications, notably in renal and retinal conditions. The incremental cost-effectiveness ratio was $46 533 per quality-adjusted life year gained with BIAsp 70/30 vs. glargine (for patients with baseline HbA1c >/= 8.5%, it was $34 916). Total lifetime costs were compared to efficacy rates in both arms as a ratio, which revealed that the lifetime cost per patient treated successfully to target HbA1c levels of <7.0% and 相似文献   

A rationale for continuing mass antibiotic distributions for trachoma

Background

Fungal infections are diagnosed increasingly often in patients affected by hematological diseases and their mortality has remained high. The recent development of new antifungal drugs gives the clinician the possibility to assess the combination of antifungal drugs with in-vitro or in animal-model synergistic effect.

Methods

We analyzed retrospectively the safety and efficacy of caspofungin-based combination therapy in 40 children and adolescents, most of them were being treated for a malignant disease, who developed invasive aspergillosis (IA) between November 2002 and November 2005.

Results

Thirteen (32.5%) patients developed IA after hematopoietic stem cell transplantation (HSCT), 13 after primary diagnosis, usually during remission-induction chemotherapy, and 14 after relapse of disease. Severe neutropenia was present in 31 (78%) out of the 40 patients. IA was classified as probable in 20 (50%) and documented in 20 (50%) patients, respectively. A favorable response to antifungal therapy was obtained in 21 patients (53%) and the probability of 100-day survival was 70%. Different, though not significant, 100-day survival was observed according to the timing of diagnosis of IA: 51.9% after HSCT; 71.4% after relapse; and 84.6% after diagnosis of underlying disease, p 0.2. After a median follow-up of 0.7 years, 20 patients are alive (50%). Overall, the combination therapy was well tolerated. In multivariate analysis, the factors that were significantly associated to a better overall survival were favorable response to antifungal therapy, p 0.003, and the timing of IA in the patient course of underlying disease, p 0.04.

Conclusion

This study showed that caspofungin-based combination antifungal therapy is an effective therapeutic option also for pediatric patients with IA. These data need to be confirmed by prospective, controlled studies.