Telecardiology applied to a region-wide public emergency health-care service

Aim To assess feasibility and reliability of telecardiology technologies applied to a region-wide public emergency health-care service. Methods About 27,841 patients from all over Apulia (19.362 km², 4 million inhabitants) were referred from October 2004 until April 2006 to public emergency health-care number “118” and underwent ECG evaluation according to a previously fixed inclusion protocol. Data recorded were transmitted with mobile telephone support to a telecardiology “hub” active 24-h a day. Hospitalization or further examinations were arranged by emergency physicians on the basis of ECG diagnosis and consultation. Results Thirty-nine percent of patients complained of chest pain (CP) or epigastric pain, 26% loss of consciousness, 10% breathlessness, and 7% palpitations. Atrial fibrillation (AF) was diagnosed in 11.68% of patients and ST-elevation acute myocardial infarction (STEMI) in 1.91%. Among patients with CP, ECG showed STEMI in only 3.84% of cases, theoretically eligible for fibrinolysis or primary PCI; patients with STEMI complained of CP in 78.94% of cases. Of the patients, 65.28% with STEMI were from small towns without coronary care units, thus benefiting from an immediate pre-hospital diagnosis. Among patients with palpitations, only 10.27% of subjects showed ECG signs of supra-ventricular tachycardia and 25.18% of AF; other subjects avoided further improper hospitalization or emergency department monitoring. Conclusions This first region-wide leading experience shows the feasibility and reliability of telecardiology applied to a public emergency health-care service. Telemedicine protocols would probably be useful in lowering the number of improper hospitalizations and shortening delay in the diagnosis process of some heart diseases.     

Role of the basolateral nucleus of the amygdala in endocannabinoid-mediated stress-induced analgesia

Recent work in our laboratories has demonstrated that an opioid-independent form of stress-induced analgesia (SIA) is mediated by endogenous ligands for cannabinoid receptors-anandamide and 2-arachidonoylglycerol (2-AG) [A.G. Hohmann, R.L. Suplita, N.M. Bolton, M.H. Neely, D. Fegley, R. Mangieri, J.F. Krey, J.M. Walker, P.V. Holmes, J.D. Crystal, A. Duranti, A. Tontini, M. Mor, G. Tarzia, D. Piomelli, An endocannabinoid mechanism for stress-induced analgesia, Nature 435 (2005) 1108-1112]. The present study was conducted to examine the contribution of cannabinoid CB1 receptors in the basolateral nucleus of the amygdala (BLA) and central nucleus of the amygdala (CeA) to nonopioid SIA. SIA was induced by continuous footshock (3 min 0.9 mA) and quantified behaviorally using the tail-flick test. Microinjection of the CB1 antagonist/inverse agonist rimonabant (SR141716A) into the BLA, a limbic forebrain region with high densities of CB1 receptors, suppressed SIA relative to control conditions. By contrast, the same dose administered into the CeA, where CB1 immunoreactivity is largely absent, or outside the amygdala did not alter SIA. To examine the contribution of endocannabinoids in the BLA to SIA, we used selective pharmacological inhibitors of the anandamide-degrading enzyme fatty-acid amide hydrolase (FAAH) and the 2-arachidonoylglycerol-degrading enzyme monoacylglycerol lipase (MGL). The FAAH inhibitor URB597 and MGL inhibitor URB602, at doses that enhanced SIA following microinjection in the midbrain periaqueductal gray, did not alter SIA relative to control conditions. Our findings suggest that CB1 receptors in the BLA but not the CeA contribute to SIA, but pharmacological inhibition of endocannabinoid degradation at these sites does not affect the expression of stress antinociception.     

Hemispheric cerebellar rTMS to treat drug-resistant epilepsy: case reports

Electrical stimulation of the cerebellar cortex by implanted electrodes has been shown to ameliorate refractory epilepsy. We investigated the potential therapeutic role of high-frequency cerebellar rTMS in patients affected by refractory epilepsy due to single or multiple foci. Six patients, three with single and three with multiple epileptic foci, underwent 20 rTMS sessions. Each session was given daily, excluding weekends, and consisted of two trains of 50 stimuli (5 Hz frequency and 90% motor threshold intensity), separated by 50s interval. rTMS was delivered through a focal coil (2 cm below and lateral to the inion) bilaterally in patients with multiple foci (two trains for hemisphere: 100 stimuli each side) and contralaterally to the epileptic focus in the others. Seizure frequency was monitored four weeks before stimulation (pre-rTMS), during the four-week treatment (rTMS) and four weeks after the treatment (post-rTMS). The rTMS over the cerebellar cortex was associated with a significant decrease of rTMS versus pre-rTMS seizure frequency both in patients with single and multiple epileptic foci. However, during the post-rTMS period seizure frequency was back to the pre-rTMS frequency. Although the results are still preliminary, they encourage further studies on larger series of patients. In particular, this rTMS approach, as compared with others, might be more useful in patients with multiple epileptic foci.     

Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation

Hepatocyte growth factor (HGF), a pleiotropic cytokine of mesenchymal origin promoting migration, proliferation, and survival in a wide spectrum of cells, can also modulate different biological responses in stem cells, but the mechanisms involved are not completely understood so far. In this context, we show that short-term exposure of mesenchymal stem cells (MSCs) to HGF can induce the activation of its cognate Met receptor and the downstream effectors ERK1/2, p38MAPK, and PI3K/Akt, while long-term exposure to HGF resulted in cytoskeletal rearrangement, cell migration, and marked inhibition of proliferation through the arrest in the G1-S checkpoint. When added to MSCs, the K252A tyrosine kinase inhibitor prevented HGF-induced responses. HGF's effect on MSC proliferation was reversed by p38 inhibitor SB203580, while the effects on cell migration were abrogated by PI3K inhibitor Wortmannin, suggesting that HGF acts through different pathways to determine its complex effects on MSCs. Prolonged treatment with HGF induced the expression of cardiac-specific markers (GATA-4, MEF2C, TEF1, desmin, alpha-MHC, beta-MHC, and nestin) with the concomitant loss of the stem cell markers nucleostemin, c-kit, and CD105.     

Bio-Oss collagen and orthodontic movement for the treatment of infrabony defects in the esthetic zone

The aim of the present study was to evaluate whether it is possible to orthodontically move migrated teeth into infrabony defects augmented with a biomaterial. Three adult patients suffering from chronic periodontitis were treated. Each of the patients presented with an infrabony defect adjacent to a migrated maxillary central incisor. After cause-related therapy was completed, a surgical procedure was performed using the papilla preservation technique. The defects were filled with a collagen bovine bone mineral; after 2 weeks, an orthodontic device was activated using light, continuous forces. Orthodontic treatment time varied from 4 to 9 months; during this period, patients were enrolled in an oral hygiene recall program. At baseline and 6 months after the end of therapy, probing pocket depths (PPD) and clinical attachment levels (CAL) were assessed. In addition, the vertical and horizontal dimensions of the defects were measured on standardized radiographs. Residual mean PPD was 3.33 mm, with a mean reduction of 3.67 mm. Mean CAL gain was 4.67 mm. Radiologic vertical and horizontal bone fills were, on average, 3.17 mm and 2.0 mm, respectively. The present case series shows the effectiveness of a combined periodontic-orthodontic approach for the treatment of infrabony defects. Reduction of PPD to physiologic values, CAL gain, and radiologic defect resolution were obtained. No detrimental effects from the orthodontic movement were observed on the augmentation material.     

Looking for celiac disease: diagnostic accuracy of two rapid commercial assays

BACKGROUND: Early diagnosis and treatment with gluten-free diet reduces mortality and the prevalence of associated disorders in celiac disease (CD). A simple "in the office" test of anti-transglutaminase antibodies might be of great help in first-line screening for CD. AIMS: We evaluated the sensitivity and specificity of two commercial kits based, respectively, on rapid detection of IgA-IgG anti-human-transglutaminase antibodies (anti-h-tTG) in serum and IgA anti-h-tTG antibody in one drop of whole blood. These assays were compared to a well-established enzyme-linked immunosorbent assay technique. METHODS: Serum samples were analyzed from 114 biopsy-confirmed celiacs, 120 healthy controls, 20 first-degree relatives of celiacs, and 75 diseased controls. The whole blood samples were analyzed from 51 biopsy-confirmed celiacs and 100 controls. RESULTS: The serum-based test was positive in all 114 celiacs (sensitivity 100%). Among the controls there were seven healthy blood donors, one first-degree relative, and three diseased controls who tested positive (specificity 94.9%). The blood drop-based assay testing IgA antibodies was positive in 46 of 51 (sensitivity 90.2%), and since three of the five patients testing negative had total IgA deficiency, the sensitivity value can be increased to 95.8%. All 100 controls tested negative (specificity 100%). CONCLUSIONS: The commercial kits described here produce high values of sensitivity and specificity, offering the general practitioner who suspects a possible case of CD the real possibility to look for anti-h-tTG antibodies in his own medical office during a standard visit at a satisfyingly low cost.     

The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens

Pentraxins are soluble pattern recognition receptors with a dual role: protection against extracellular microbes and autoimmunity. The mechanisms by which they accomplish these tasks are not yet fully understood. Here we show that the prototypic long pentraxin PTX3 is specifically recruited at both sides of the phagocytic synapse between dendritic cells (DCs) and dying cells and remains stably bound to the apoptotic membranes (estimated half-time > 36 hours). Apoptotic cells per se influence the production of PTX3 by maturing DCs. When both microbial stimuli and dying cells are present, PTX3 behaves as a flexible adaptor of DC function, regulating the maturation program and the secretion of soluble factors. Moreover a key event associated with autoimmunity (ie, the cross-presentation of epitopes expressed by apoptotic cells to T cells) abates in the presence of PTX3, as evaluated using self, viral, and tumor-associated model antigens (vinculin, NS3, and MelanA/MART1). In contrast, PTX3 did not influence the presentation of exogenous soluble antigens, an event required for immunity against extracellular pathogens. These data suggest that PTX3 acts as a third-party agent between microbial stimuli and dying cells, contributing to limit tissue damage under inflammatory conditions and the activation of autoreactive T cells.