Peripheral nerve stimulation: lead position monitoring by reconstruction CT angiography—A technical report

Background  The authors investigated the possibility of improving positioning of stimulation leads in patients with chronic neuropathic peripheral nerve pain and good pain relief from implantation of a peripheral nerve stimulator (PNS). Methods  This pilot study includes four patients suffering from Chronic Regional Pain Syndrome type II (CRPS II) or neuropathic mononeuropathy treated with PNS therapy. The affected extremities and corresponding implantation sites were examined using computer tomographic scans (CT), additional CT angiography (CTA), reconstruction techniques and postprocessing procedures. Results  It was possible to prove a close relation between the implanted device and the neurovascular bundle in each of these cases. Thus, indirect lead position control was obtained. Conclusions  Computer tomographic techniques represent a reliable method for the position control of implanted peripheral nerve electrodes. Hence, this procedure should surpass general radiographies in detecting lead displacements.     

Modified Vaccination Technique for Prophylactic and Therapeutic Applications to Combat Endogenous Antigen–Induced Disorders

Public health can be protected most effectively through vaccination programmes. However, while presently available vaccination techniques protects the individual by provoking immune responses against exogenous antigens (ags), such as those associated with certain bacteria and viruses, they cannot protect against or treat mishaps caused by endogenous ag. Recently, Barabas and colleagues have developed a new vaccination method, called modified vaccination technique (MVT), which allows the presentation of disease causing agents in such a way as to initiate and maintain desired immune response outcomes even in the context of mishaps associated with endogenous ag. For example, in an experimental autoimmune kidney disease, the MVT downregulated/terminated pathogenic immune responses that were causing morphological and functional changes of the kidney. The MVT promises, with appropriate case‐specific modifications, both preventative and curative applications for ailments, such as endogenous ag initiated mishaps (i.e. autoimmune diseases and cancer) and diseases caused by chronic infection, that are presently only treatable with drugs. To achieve specific immune responses, purified components of the vaccine (ag and antibodies) must be produced and assembled into immune complexes having the potential of inducing predetermined corrective immune response outcomes.     

Ghrelin action in the brain controls adipocyte metabolism

Many homeostatic processes, including appetite and food intake, are controlled by neuroendocrine circuits involving the CNS. The CNS also directly regulates adipocyte metabolism, as we have shown here by examining central action of the orexigenic hormone ghrelin. Chronic central ghrelin infusion resulted in increases in the glucose utilization rate of white and brown adipose tissue without affecting skeletal muscle. In white adipocytes, mRNA expression of various fat storage-promoting enzymes such as lipoprotein lipase, acetyl-CoA carboxylase alpha, fatty acid synthase, and stearoyl-CoA desaturase-1 was markedly increased, while that of the rate-limiting step in fat oxidation, carnitine palmitoyl transferase-1alpha, was decreased. In brown adipocytes, central ghrelin infusion resulted in lowered expression of the thermogenesis-related mitochondrial uncoupling proteins 1 and 3. These ghrelin effects were dose dependent, occurred independently from ghrelin-induced hyperphagia, and seemed to be mediated by the sympathetic nervous system. Additionally, the expression of some fat storage enzymes was decreased in ghrelin-deficient mice, which led us to conclude that central ghrelin is of physiological relevance in the control of cell metabolism in adipose tissue. These results unravel the existence of what we believe to be a new CNS-based neuroendocrine circuit regulating metabolic homeostasis of adipose tissue.     

Insulinemia and leptinemia or of undernutrition in geriatric patients: markers of the metabolic syndrome or of undernutrition?

The metabolic syndrome (MS) describes a cluster of metabolic disturbances including type 2 diabetes and/or insulin resistance, hypertension, dyslipidemia and obesity, which predict a high risk of cardiovascular disorders. The associated hyperinsulinemia and hyperleptinemia may contribute to the cardiovascular risk. However, the operational value of the MS in elderly patients is questionable. We therefore investigated the prevalence and significance of the MS in geriatric care. In a survey of 98 consecutive admissions of diabetic patients, <40% had a MS; this is a low value compared to younger diabetic adults, due to a low prevalence of obesity and dyslipidemia. We found a high prevalence of low BMI (<20 kg/m2), hypoalbuminemia and low total cholesterol levels, suggesting that the MS may be modified by undernutrition. The interplay between the MS and undernutrition was further studied in 30 non-diabetic patients. Both leptinemia and insulin resistance indexes (HOMA-IR and QUICKI) were strongly associated with BMI and body fat (measured by Bioelectrical impedance Analysis). BMI, leptinemia and insulin resistance indexes were associated with the Mini Nutritional Assessment (MNA) score. Thus, undernutrition is associated with low leptin and insulin levels and may obscure the association of these parameters with cardiovascular risk. In conclusion, the MS has a low prevalence in our population of elderly diabetic patients, and is of questionable prognostic value. It can be oveshadowed by undernutrition, which is associated with low body weight, leptinemia and insulin resistance indexes. Prevention of undernutrition and/or adjustment to its consequences should receive higher priority in the care of elderly diabetic patients.     

Bradykinin and angiotensin-converting enzyme inhibition in cardioprotection

OBJECTIVES:

To show that angiotensin-converting enzyme (ACE) inhibition potentiates subthreshold ischemic preconditioning (IPC) via the elevation of bradykinin activity, leading to a fully delayed cardioprotective response.

METHODS:

On day 1 of the experiment, pigs were subjected to sham (group 1, controls) or IPC protocols. In groups 2 and 3, 4×5 min and 2×2 min of IPC, respectively, were elicited by occluding the left anterior descending coronary artery with percutaneous transluminal coronary angioplasty inflatable balloon catheter. Group 4 was subjected to the ACE inhibitor perindoprilate only. In group 5, the pigs were pretreated with perindoprilate (0.06 mg/kg) and then subjected to 2×2 min IPC. In group 6, intracoronary HOE 140 (a selective bradykinin B₂ receptor antagonist) was added before the perindoprilateaugmented subthreshold (2×2 min) PC stimulus. On the second day, all animals underwent 40 min left anterior descending coronary artery ligation and 3 h reperfusion, followed by infarct size analysis using triphenyl tetrazolium chloride staining.

RESULTS:

The rates of infarct size and risk zone were the following in the experimental groups: group 1, 42.8%; group 2,19.5% (P<0.05); group 3, ischemia/reperfusion (I/R) 33.4%; group 4, I/R 18.4% (P<0.05); group 5, I/R 31.2%; and group 6, I/R 36.3%. A significant increase of nuclear factor kappa B activation in groups 2 and 4 was seen.

CONCLUSIONS:

Results confirm that ACE inhibitors do not give total pharmacological IPC, but they enhance the induction effect of small ischemic insults, which raises the ischemic tolerance of myocardium. It was determined that enhanced bradykinin activity leads to downstream nuclear factor kappa B activation in this model.     

Metabolic changes in the lower esophageal sphincter influencing the result of anti-reflux surgical interventions in chronic gastroesophageal reflux disease

AIM: With the availability of a minimally invasive approach, anti-reflux surgery has recently experienced a renaissance as a cost-effective alternative to life-long medical treatment in patients with gastroesophageal reflux disease (GERD). We are not aware of the fact whether reflux episodes causing complaints for a long time i.e., at least for one year are associated with metabolic changes in the lower esophageal sphincter, and if so, whether these may influence functional results achieved after anti-reflux surgery. METHODS: Between 1 January 2001 and 31 December 2002 we performed anti-reflux surgery on 79 patients. Muscle samples were taken from the lower esophageal sphincter (LES) in 33 patients during anti-reflux surgery. Inclusion criteria were: LES resting pressure below 10 mmHg and a marked, pH proven acid exposure to the esophagus of at least one year's duration, causing subjective complaints and requiring continuous proton pump inhibitor treatment. Control samples were obtained from muscle tissue in the gastroesophageal junction that had been removed from 17 patients undergoing gastric or esophageal resection. Metabolic and lysosomal enzyme activities and special protein concentrations 16 parameters in total were evaluated in tissue taken from control specimens and tissue taken from patients with GERD. The biochemical parameters of these intra-operative biopsies were used to correlate the results of anti-reflux operations (Visick Ⅰ and Ⅱ-Ⅲ). RESULTS: In the reflux-type muscle, we found a significant increase of the energy-enzyme activities e.g., creatine kinase, lactate dehydrogenase, β-hydroxybutyrate dehydrogenase, and aspartate aminotransaminase-. The concentration of the structural protein S-100 and the myofibrillar protein troponin Ⅰ were also significantly increased. Among lysosomal enzymes, we found that the activities of cathepsin B, tripeptidyl-peptidase Ⅰ, dipeptidyl-peptidase Ⅱ, β-hexosaminidase B, β-mannosidase and β-galactosidase were significantly decreased as compared to the control LES muscles. By analyzing the activity values of the 9 patients in Visick groups Ⅱ and Ⅲ at two months post-surgery, we found a significant increase in the activity of the so-called energy-enzyme values and in the concentration of structural and myofibrillar proteins as compared to the rest of the reflux patients. CONCLUSION: Our results call attention to the metabolic changes that occurred in the LES muscles of reflux patients. The developing hypertrophy-like changes of LES muscles may be a reason for complaints after anti-reflux surgery, which consisted mainly of reports of persisting dysphagia.