Pulmonary position cryopreserved homografts: durability in pediatric Ross and non-Ross patients

OBJECTIVE: The purpose of this study was to evaluate the outcome and risk factors for implant failure in pediatric patients who underwent pulmonary position homograft placement for right ventricular outflow tract obstruction compared with conduit placement as a component of the Ross operation. Actuarial 5-year survivals for cryopreserved right ventricle-to-pulmonary artery homografts range from 55% to 94% at all ages. It is not known whether there is a difference in homograft durability when utilized for right ventricular outflow tract obstruction or as part of the Ross operation. METHODS: The records of all pediatric patients receiving a right ventricle-to-pulmonary artery homograft from July 1989 through October 2003 were reviewed. Ninety-eight consecutive patients were studied (26 Ross, 72 non-Ross). In addition to Ross versus non-Ross comparisons, other potential risk factors for homograft failure analyzed included age at operation, follow-up time, type of surgery, and homograft type and size. RESULTS: Ross and non-Ross patients were comparable in age at the time of the operation and follow-up time. Homograft failure rates were 12% and 51% for Ross and non-Ross patients, respectively. Freedom from reintervention was 93% in the Ross and 66% in the non-Ross group at 5 years (P = .019). On multivariate analysis, non-Ross operation and age less than 2 years were significant predictors of homograft failure. CONCLUSIONS: 1. Pediatric patients undergoing the Ross operation have longer homograft survival than pediatric patients treated for right ventricular outflow tract obstruction, independent of age. 2. Homografts placed in patients less than 2 years of age have shorter homograft survival.     

Mechanical insufflation-exsufflation improves outcomes for neuromuscular disease patients with respiratory tract infections

OBJECTIVES: The efficacy of mechanical insufflation-exsufflation, in addition to standard chest physical treatments, was investigated as a first-line intervention for patients with neuromuscular diseases with respiratory tract infections and airway mucous encumbrance. DESIGN: The short-term outcomes of 11 consecutive neuromuscular disease patients with respiratory tract infections and tracheobronchial mucous encumbrance who were administered mechanical insufflation-exsufflation and conventional chest physical treatments in an intensive care unit were compared with the outcomes of 16 historical matched controls who had received chest physical treatments alone. Treatment failure was defined as the need for cricothyroid "minitracheostomy" or endotracheal intubation, despite treatment. The number of subjects administered bronchoscopy-assisted aspiration during the hospital stay was also compared. RESULTS: Treatment failure was significantly lower (P < 0.05) in the mechanical insufflation-exsufflation group than in the conventional chest physical treatments group (2/11 vs. 10/16 cases). The use of bronchoscopy-assisted aspiration was similar in the two groups (5/11 vs. 6/16 cases). Mechanical insufflation-exsufflation did not produce serious side effects and was well tolerated by all subjects. CONCLUSIONS: Provision of mechanical insufflation-exsufflation in combination with standard chest physical treatments may improve the management of airway mucous encumbrance in neuromyopathic patients; its use should be included in the noninvasive approach to treatment of respiratory tract infections with impaired mucous clearance.     

Terpinen-4-ol, the main component of Melaleuca alternifolia (tea tree) oil inhibits the in vitro growth of human melanoma cells

The search for innovative therapeutic approaches based on the use of new substances is gaining more interest in clinical oncology. In this in vitro study the potential anti-tumoral activity of tea tree oil, distilled from Melaleuca alternifolia, was analyzed against human melanoma M14 WT cells and their drug-resistant counterparts, M14 adriamicin-resistant cells. Both sensitive and resistant cells were grown in the presence of tea tree oil at concentrations ranging from 0.005 to 0.03%. Both the complex oil (tea tree oil) and its main active component terpinen-4-ol were able to induce caspase-dependent apoptosis of melanoma cells and this effect was more evident in the resistant variant cell population. Freeze-fracturing and scanning electron microscopy analyses suggested that the effect of the crude oil and of the terpinen-4-ol was mediated by their interaction with plasma membrane and subsequent reorganization of membrane lipids. In conclusion, tea tree oil and terpinen-4-ol are able to impair the growth of human M14 melanoma cells and appear to be more effective on their resistant variants, which express high levels of P-glycoprotein in the plasma membrane, overcoming resistance to caspase-dependent apoptosis exerted by P-glycoprotein-positive tumor cells.     

In vivo administration of liposomal vincristine sensitizes drug-resistant human solid tumors

Here we evaluated the antitumor efficacy of vincristine (VCR) encapsulated in sphingomyelin/cholesterol liposomes (SM/Chol) on drug-resistant human solid tumors. We firstly used the M14 human melanoma line and the counterpart resistant derivative, M14/R. The M14/R, selected after doxorubicin exposure, was cross resistant to VCR: the in vitro treatment with free VCR reduced the survival of M14, while M14/R line was completely resistant to VCR. Encapsulation in liposomes improved the efficacy of VCR in M14 cells and sensitized the M14/R line to the drug. Experiments in vivo confirmed these results. The treatment of M14 bearing mice with VCR resulted in marked reduction of tumor growth, while no antitumoral effect was observed in M14/R tumors. The administration of VCR encapsulated in liposomes was able to sensitize M14/R tumors to the drug, the antitumoral effect being comparable to that observed in M14 tumors after the same treatment. By injecting animals with the same dose of liposomal VCR fractionated into 3 daily injections and administering repeated cycles of treatment, to a marked improvement of the antitumor activity of liposomal VCR was observed. TUNEL assay in tumor sections indicated that the improved efficacy of liposomal VCR was related to the induction of massive necrosis and apoptosis. To confirm the efficacy of liposomal VCR on drug-resistant tumors, MCF7 breast and LoVo colon carcinomas, sensitive and resistant to VCR treatment, were also employed. The results showed that the treatment with liposomal VCR of mice bearing breast or colon resistant tumors reduced the tumor mass and delayed the tumor regrowth to the same extent observed in the sensitive counterpart. Together, these results demonstrate the ability of VCR encapsulated in liposomes in sensitizing drug resistant tumors of different histotypes.     

Modification to the Fontan procedure for the prophylaxis of intra-atrial reentrant tachycardia: short-term results of a prospective randomized blinded trial

OBJECTIVES: We evaluated the feasibility, safety, and short-term efficacy of an interventional atrial incision placed at the time of the Fontan operation to reduce the development of intra-atrial reentrant tachycardia. METHODS: This prospective randomized blinded trial was conducted in patients with congenital heart disease undergoing an initial lateral tunnel Fontan. Intervention patients underwent a lateral tunnel Fontan with an interventional atrial incision/cryoablation from the atriotomy to the right atrioventricular annulus. Controls underwent a standard lateral tunnel Fontan. Safety of the intervention was monitored. Short-term efficacy was determined by comparisons of conduction block across the incision area and spontaneous or inducible atrial arrhythmias. RESULTS: There were no significant differences between intervention (n = 21, median 2.4 years, range 0.8-3.9) and controls (n = 21, median 2.7 years, range 1.5-13.9) in age, type of heart disease, surgical parameters, or postoperative outcomes. Safety parameters showed no difference between groups in number or severity of adverse events. Short-term efficacy included evidence of conduction block with a longer conduction time across the incision area in intervention patients (median 97 ms, range 35-160) compared with controls (median 40 ms, range 8-77, P =.0001). No intervention patients had spontaneous or inducible intra-atrial reentrant tachycardia versus 2 controls (0/21 versus 2/21, P = NS). CONCLUSIONS: An interventional atrial incision to reduce intra-atrial reentrant tachycardia in the Fontan operation was feasible and safe. The intervention changed the atrial substrate as shown by an increase in conduction time. Short-term results showed a low incidence of intra-atrial reentrant tachycardia in all patients. Longer follow-up is necessary to assess clinical efficacy.     

Insulin generates free radicals by an NAD(P)H, phosphatidylinositol 3'-kinase-dependent mechanism in human skin fibroblasts ex vivo

Oxidative stress may be involved in the development of vascular complications associated with diabetes; however, the molecular mechanism responsible for increased production of free radicals in diabetes remains uncertain. Therefore, we examined whether acute hyperinsulinemia increases the production of free radicals and whether this condition affects proliferative extracellular signal-regulated kinase (ERK-1 and -2) signaling in human fibroblasts in vitro. Insulin treatment significantly increased intracellular superoxide anion (O(2)(-)) production, an effect completely abolished by Tiron, a cell-permeable superoxide dismutase (SOD) mimetic and by polyethylene glycol (PEG)-SOD, but not by PEG catalase. Furthermore, insulin-induced O(2)(-) production was attenuated by the NAD(P)H inhibitor apocynin, but not by rotenone or oxypurinol. Inhibition of the phosphatidylinositol 3'-kinase (PI 3'-kinase) pathway with LY294002 blocked insulin-stimulated O(2)(-) production, suggesting a direct involvement of PI 3'-kinase in the activation of NAD(P)H oxidase. The insulin-induced free radical production led to membranous translocation of p47phox and markedly enhanced ERK-1 and -2 activation in human fibroblasts. In conclusion, these findings provided direct evidence that elevated insulin levels generate O(2)(-) by an NAD(P)H-dependent mechanism that involves the activation of PI 3'-kinase and stimulates ERK-1- and ERK-2-dependent pathways. This effect of insulin may contribute to the pathogenesis and progression of cardiovascular disease in the insulin resistance syndrome.     

Evidence for a protective role played by the Na+/Ca2+ exchanger in cerebral ischemia induced by middle cerebral artery occlusion in male rats

In the present paper, the role played by Na+/Ca2+ exchanger (NCX) in focal cerebral ischemia was investigated. To this aim, permanent middle cerebral artery occlusion (pMCAO) was performed in male rats. The effects on the infarct volume of some inhibitors, such as tyrosine-6 glycosylated form of the exchanger inhibitory peptide (GLU-XIP), benzamil derivative (CB-DMB) and diarylaminopropylamine derivative (bepridil), and of the NCX activator, FeCl3, were examined. FeCl3, CB-DMB, bepridil and GLU-XIP, a modified peptide synthesized in our laboratory in order to facilitate its entrance into the cells through the glucose transporter, were intracerebroventricularly (i.c.v.) infused. FeCl3 (10 microg/kg) was able to reduce the extension of brain infarct volume. This effect was counteracted by the concomitant icv administration of CB-DMB (120 microg/kg). All NCX inhibitors, GLU-XIP, CB-DMB and bepridil, caused a worsening of the brain infarct lesion. These results suggest that a stimulation of NCX activity may help neurons and glial cells that are not irreversibly damaged in the penumbral zone to survive, whereas its pharmacological blockade can compromise their survival.     

Hippocampal and striated skeletal muscle changes in fatty acid composition induced by ethanol in alcohol-preferring rats

Chronic ethanol intake affects various organ systems of the body. The present study evaluated modifications of fatty acid concentrations both in brain and striated skeletal muscles of rats genetically selected for voluntary high ethanol intake. Three groups of rats were tracked for 10 weeks of access to ethanol only as fluid (group 1) to free choice of ethanol and water (group 2) or to water only (group 3). At the end of the period, the animals were sacrificed and their brain hippocampus and striated skeletal muscles were removed and fatty acid content of these tissues was determined. Long-chain fatty acid content increased in the hippocampus while it decreased in the striated skeletal muscles. Short chain fatty acid content decreased in the hippocampus while short chain fatty acid content increased in the striated skeletal muscles. The data show that brain and striated skeletal muscles differently modulate fatty acid content perhaps because these areas utilize different cell membrane functionality regulation systems.     

Role Utilization of Nurses in Public Psychiatry

This study examined the professional, work and organizational characteristics, and the actual and preferred work activities of nurses employed by one state mental health agency. Findings include neutral ratings by this older and experienced group of nurses in relation to job satisfaction, work autonomy, and organizational commitment regardless of educational background or work setting. Specific activities of the nurses varied appropriately based on education, but differences emerged among functions performed by nurses in inpatient and community settings. All nurses preferred to increase their direct care activities and significantly reduce their clerical activities. Factors related to the appropriate utilization of public sector psychiatric nurses are analyzed.