Late-onset periodic asystolia during vagus nerve stimulation

Cardiac changes may occasionally occur during vagus nerve stimulation (VNS) used in epileptic patients. As they can be potentially life-threatening, it is important to detect them, and this is why an intraoperative test is performed during the implantation. Few cases of asystole during this test have been described. Only one patient with late-onset bradyarrythmia caused by VNS has been reported. This patient had been implanted 2 years and 4 months before the episode. We present another case of late asystole in a patient whose VNS had been implanted 9 years before the arrhythmia onset. In our patient, each run of stimulation produced bradyarrhythmias and very often severe asystolia due to atrium-ventricular block.     

Differentiating between malignant and idiopathic pleural effusions: the value of diagnostic procedures

BACKGROUND: Which diagnostic procedures should be used to differentiate between idiopathic and malignant pleural effusions, is not well established. AIM: To identify which parameters allow differentiation between idiopathic and malignant pleural effusions. DESIGN: Case-note review. METHODS: Over a 12-year period, we treated 1014 consecutive pleural effusion patients, of whom 346 were diagnosed as having an idiopathic or malignant aetiology. We analysed medical history, chest X-ray, pleural fluid analysis (biochemical, microbiological and cytological), chest CT scan and additional examinations that were used according to clinical findings, and compared them with the eventual diagnosis and outcome. RESULTS: Eighty-three patients with idiopathic effusions and 263 with malignant effusions were included. Idiopathic pleural effusion resolved in 47 patients, improved in 20 and persisted in 16. Biochemical pleural fluid analysis did not predict these outcomes. A history of neoplasm, chest X-ray and CT features, as well as additional examinations according to clinical findings, established a diagnosis or suspicion of malignancy in 256 (97.7%) of the 263 patients who received a diagnosis of malignant effusion. Diagnostic thoracoscopy was helpful in seven patients in whom malignant disease was strongly suspected, despite the absence of other pathological findings. DISCUSSION: Non-invasive complementary examinations generally allowed accurate differentiation between malignant and idiopathic effusions. Patients with idiopathic pleural effusions generally had favourable outcomes.     

GLP-1 and Adiponectin: Effect of Weight Loss After Dietary Restriction and Gastric Bypass in Morbidly Obese Patients with Normal and Abnormal Glucose Metabolism

Background  It has been proposed that there is improvement in glucose and insulin metabolism after weight loss in patients who underwent diet restriction and bariatric surgery. Methods  Eleven normal glucose tolerant (NGT) morbidly obese patients [body mass index (BMI), 46.1 ± 2.27 g/m²] and eight abnormal glucose metabolism (AGM) obese patients (BMI, 51.20 kg/m²) were submitted to diet-restriction and bariatric surgery. Prospective study on weight loss changes, over the glucose, insulin metabolism, glucagon-like peptide-1 (GLP-1), and adiponectin levels were evaluated by oral glucose tolerance test during three periods: T1 (first evaluation), T2 (pre-surgery), and T3 (9 months after surgery). Results  Insulin levels improved after surgery. T1 was 131.1 ± 17.60 pmol/l in the NGT group and 197.57 ± 57.94 pmol/l in the AGM group, and T3 was 72.48 ± 3.67 pmol/l in the NGT group and 61.2 ± 9.33 pmol/l in the AGM group. The major reduction was at the first hour of the glucose load as well as fasting levels. At 9 months after surgery (T3), GLP-1 levels at 30 and 60 min had significantly increased in both groups. It was observed that the AGM group had higher levels of GLP-1 at 30 min (34.06 ± 6.18 pmol/l) when compared to the NGT group (22.69 ± 4.04 pmol/l). Homeostasis model assessment of insulin resistance from the NGT and AGM groups had a significant reduction at periods T3 in relation to T1 and T2. Adiponectin levels had increased concentration in both groups before and after surgical weight loss. However, it did not have any statistical difference between periods T1 vs. T2. Conclusions  Weight loss by surgery leads to improvement in the metabolism of carbohydrates in relation to sensitivity to the insulin, contributing to the reduction of type 2 diabetes incidence. This improvement also was expressed by the improvement of the levels of adiponectin and GLP-1.     

Liposome‐bound APO2L/TRAIL is an effective treatment in a rabbit model of rheumatoid arthritis

Objective

We previously observed that T lymphocytes present in synovial fluid (SF) from patients with rheumatoid arthritis (RA) were sensitive to APO2L/TRAIL. In addition, there was a drastic decrease in the amount of bioactive APO2L/TRAIL associated with exosomes in SF from RA patients. This study was undertaken to evaluate the effectiveness of bioactive APO2L/TRAIL conjugated with artificial lipid vesicles resembling natural exosomes as a treatment in a rabbit model of antigen‐induced arthritis (AIA).

Methods

We used a novel Ni²⁺‐(N‐5‐amino‐1‐carboxypentyl)‐iminodiacetic acid)–containing liposomal system. APO2L/TRAIL bound to liposomes was intraarticularly injected into the knees of animals with AIA. One week after treatment, rabbits were killed, and arthritic synovial tissue was analyzed.

Results

Tethering APO2L/TRAIL to the liposome membrane increased its bioactivity and resulted in more effective treatment of AIA compared with soluble, unconjugated APO2L/TRAIL, with substantially reduced synovial hyperplasia and inflammation in rabbit knee joints. The results of biophysical studies suggested that the increased bioactivity of APO2L/TRAIL associated with liposomes was due to the increase in the local concentration of the recombinant protein, augmenting its receptor crosslinking potential, and not to conformational changes in the protein. In spite of this increase in bioactivity, the treatment lacked systemic toxicity and was not hepatotoxic.

Conclusion

Our findings indicate that binding APO2L/TRAIL to the liposome membrane increases its bioactivity and results in effective treatment of AIA.