Reduced glomerular filtration rate and prior cardiovascular event entail similar risk for coronary atherosclerotic burden.

OBJECTIVE: Prior cardiovascular event and kidney dysfunction are both strong risk factors for coronary artery disease. The aim of this study is to assess coronary atherosclerotic burden in a large population of patients undergoing coronary angiography, according to prior cardiovascular event or chronic kidney disease. PATIENTS AND METHODS: We evaluated 700 consecutive patients who underwent coronary angiography (CA). Serum creatinine to estimate glomerular filtration rate (eGFR) was measured. Clinically significant coronary artery disease (CAD) was defined by the presence of a coronary lesion resulting in a luminal stenosis >50%. For the purpose of the study, the whole population was divided into 4 subgroups according to the presence/absence of eGFR <60 ml/min/1.73 m2 or prior cardiovascular event: eGFR≥60/no event (Group A), eGFR≥60/yes event (Group B), eGFR<60/no event (Group C), eGFR<60/yes event (Group D). PATIENTS: As expected, patients in group D had the worst clinical and biochemical profile. These patients also presented the highest values of urinary albumin creatinine ratio (ACR, p<0.001) and the lowest values of eGFR (p<0.01). One-hundred-ninety-six patients had three-vessel disease. Patients who had undergone PCI procedure showed a lower eGFR as compared to patients who had not (p=0.009). Considering group A as reference, the risk of having three-vessel disease was increased in group B (OR= 2.09; 95% CI 1.37-3.19), in group C, (OR= 1.80; 95% CI 1.04-3.14), and finally in group D (OR= 3.35; 95% CI 2.01-5.58). The risk carried by group C was not significantly different from that carried by Group B: OR= 0.86; 95% CI 0.5-1.5. CONCLUSIONS: In our study, low eGFR seems to have the same excess risk of prior CV event.

New generation non-stationary portable neutron generators for biophysical applications of Neutron Activation Analysis.

BACKGROUND: Neutron sources are increasingly employed in a wide range of research fields. For some specific purposes an alternative to existing large-scale neutron scattering facilities, can be offered by the new generation of portable neutron devices. SCOPE OF REVIEW: This review reports an overview for such recently available neutron generators mainly addressed to biophysics applications with specific reference to portable non-stationary neutron generators applied in Neutron Activation Analysis (NAA). MAJOR CONCLUSIONS: The review reports a description of a typical portable neutron generator set-up addressed to biophysics applications. GENERAL SIGNIFICANCE: New generation portable neutron devices, for some specific applications, can constitute an alternative to existing large-scale neutron scattering facilities. Deuterium-Deuterium pulsed neutron sources able to generate 2.5MeV neutrons, with a neutron yield of 1.0×106n/s, a pulse rate of 250Hz to 20kHz and a duty factor varying from 5% to 100%, when combined with solid-state photon detectors, show that this kind of compact devices allow rapid and user-friendly elemental analysis. "This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo".

Angiotensin II AT1 receptors mediate neuronal sensitization and sustained blood pressure response induced by a single injection of amphetamine.

A single exposure to amphetamine induces neurochemical sensitization in striatal areas. The neuropeptide angiotensin II, through AT1 receptors (AT1-R) activation, is involved in these responses. However, amphetamine-induced alterations can be extended to extra-striatal areas involved in blood pressure control and their physiological outcomes. Our aim for the present study was to analyze the possible role for AT1-R in these events using a two-injection protocol and to further characterize the proposed AT1-R antagonism protocol. Central effect of orally administered AT1-R blocker (Candesartan, 3mg/kg p.o.×5days) in male Wistar rats was analyzed by spontaneous activity of neurons within locus coeruleus. In another group of animals pretreated with the AT1-R blocker or vehicle, sensitization was achieved by a single administration of amphetamine (5mg/kg i.p. - day 6) followed by a 3-week period off drug. On day 27, after receiving an amphetamine challenge (0.5mg/kg i.p.), we evaluated: (1) the sensitized c-Fos expression in locus coeruleus (LC), nucleus of the solitary tract (NTS), caudal ventrolateral medulla (A1) and central amygdala (CeAmy); and (2) the blood pressure response. AT1-R blockade decreased LC neurons' spontaneous firing rate. Moreover, sensitized c-Fos immunoreactivity in TH+neurons was found in LC and NTS; and both responses were blunted by the AT1-R blocker pretreatment. Meanwhile, no differences were found neither in CeAmy nor A1. Sensitized blood pressure response was observed as sustained changes in mean arterial pressure and was effectively prevented by AT1-R blockade. Our results extend AT1-R role in amphetamine-induced sensitization over noradrenergic nuclei and their cardiovascular output.

A previous history of repeated amphetamine exposure modifies brain angiotensin II AT1 receptor functionality.

UNLABELLED: Previous results from our laboratory showed that angiotensin II AT1 receptors (AT1-R) are involved in the neuroadaptative changes induced by amphetamine. The aim of the present work was to study functional and neurochemical responses to angiotensin II (ANG II) mediated by AT1-R activation in animals previously exposed to amphetamine. For this purpose male Wistar rats (250-320 g) were treated with amphetamine (2.5mg/kg/day intraperitoneal) or saline for 5 days and implanted with intracerebroventricular (i.c.v.) cannulae. Seven days after the last amphetamine administration the animals received ANG II (400 pmol) i.c.v. One group was tested in a free choice paradigm for sodium (2% NaCl) and water intake and sacrificed for Fos immunoreactivity (Fos-IR) determinations. In a second group of rats, urine and plasma samples were collected for electrolytes and plasma renin activity determination and then they were sacrificed for Fos-IR determination in Oxytocinergic neurons (Fos-OT-IR). RESULTS: Repeated amphetamine exposure (a) prevented the increase in sodium intake and Fos-IR cells in caudate-putamen and accumbens nucleus induced by ANG II i.c.v. (b) potentiated urinary sodium excretion and Fos-OT-IR in hypothalamus and (c) increased the inhibitory response in plasma renin activity, in response to ANG II i.c.v. Our results indicate a possible functional desensitisation of AT1-R in response to ANG II, induced by repeated amphetamine exposure. This functional AT1-R desensitisation allows to unmask the effects of ANG II i.c.v. mediated by oxytocin. We conclude that the long lasting changes in brain AT1-R functionality should be considered among the psychostimulant-induced neuroadaptations.

Comfort and learnability assessment of a new soft robotic manipulator for minimally invasive surgery.

Laparoscopic surgeons perform precise and time consuming procedures while holding awkward poses in their upper body and arms. There is an ongoing effort to produce robotic tools for laparoscopic surgery that will simplify these tasks and reduce risk of errors to help both the surgeon and the patient. STIFF-FLOP is an ongoing EU FP7 project focusing on this by creating a stiffness controllable soft robotic manipulator. This paper reports on a study to test the soft manipulator's learnability and the effort associated with its use. The tests involved a limited prototype of the manipulator with a custom built test rig and EMG acquisition system. Task times and video recordings along with EMG waveforms from the forearm muscles of participants (n=25) were measured for objective assessment. A questionnaire was also provided to the participants for subjective assessment. The data shows that in average EMG levels were 25.9% less in RMS when using the STIFF-FLOP arm than when conventional laparoscopic tools were used. In terms of learnability, from the first to the second attempt on the STIFF-FLOP manipulator, elapsed time was reduced by an average of 32.1%. Further details and analysis of the EMG signals as well as time and questionnaire results is presented in the paper.

Prediction of functional capacity by low-dose dobutamine stress echocardiography in chronic heart failure.

AIM: The aim of this study was to determine if low-dose dobutamine stress echocardiography (LD-DSE) is associated with functional capacity in unselected elderly patients with chronic heart failure. METHODS: This was a prospective trial. Thirty five consecutive patients were included, with age >65 years and left ventricular dysfunction (12 ischemic), by blindly assessed LD-DSE and cardiopulmonary exercise testing (CPT). Contractile reserve was defined as a change (D) in wall motion score index (WMSI) = or <0.2 at peak dose dobutamine. At CPT treadmill exercise time, peak VO2, %Vo2 and VE/VCO2 slope were determined. Preserved functional capacity was defined as percent of maximal predicted O2 consumption (%VO2) >80%. Baseline NT-proBNP plasma levels were assessed. RESULTS: CPT variables were not related to clinical and baseline echocardiography characteristics but were related to DWMSI (exercise time, P=0.004; peak VO2, P=0.008; %VO2, P<0.001; VE/Vco2, P<0.001). Contractile reserve was present in 16 of 17 patients with preserved functional capacity (sensitivity=94%) and in 2 of 13 patients without (specificity=85%). Baseline NT-proBNP levels were lower in patients with contractile reserve (476+/-365 pg/mL) than in those without (1 345+/-1 219 pg/mL) (P=0.019), but were mildly related to CPT variables (P=0.049 and 0.027 with exercise time and %VO2, respectively). CONCLUSION: Contractile reserve elicited at LD-DSE is associated with functional capacity in unselected elderly patients with chronic heart failure.

After hospital: working with schools and families to support the long term needs of children with brain injuries.

Medical and rehabilitation systems care for children who sustain brain injuries. Their much needed services, however, are short in comparison with the long term needs of these children and their families. For the most part, it is schools and families who provide the long term supports to help children make the best outcomes and create a better quality of life. Professionals and families who develop collaborative models find that they can more effectively manage services for these children by carefully crafting Individual Education Plans (IEP's). Through the IEP process students' complex needs; the multiple transitions they experience; and their long term needs can be met.

Increased gut permeability in juvenile chronic arthritides. A multivariate analysis of the diagnostic parameters.

OBJECTIVE: This study was aimed at evaluating intestinal permeability (IP) in patients with oligoarticular juvenile idiopathic arthritis (o-JIA), spondyloarthropathy (SpA) associated with inflammatory bowel disease (IBD) and other forms of juvenile-onset chronic arthritiis (OIA) using the lactulose/mannitol (L/M) test in comparison with other non-invasive parameters of gut involvement. METHODS: A series of 26 children affected with o-JIA and 14 with either SpA/IBD or OIA were assessed for IP. The urinary L/M ratio was measured by gas chromatography. The erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and faecal alpha 1 antitrypsin concentrations were also evaluated. Ten o-JIA patients displayed active arthritis while in 16 the disease was under control. Among the OIA patients, 11 were affected with psoriatic arthritis and the remaining 3 with chronic reactive arthritis. 14 patients with SpA-IBD had active synovitis or spine inflammation. 14 eo-pJCA and 22 OIA and SpA-IBD patients, respectively, were receiving NSAID therapy. RESULTS: The mean L/M ratios for the Spa-IBD (0.07 +/- 0.02, mean +/- SD), OIA (0.05 +/- 0.02) and o-JIA (0.04 +/- 0.02) patients were significantly higher (p < 0.001, p = 0.022 and p = 0.01, respectively) than those found in controls (0.02 +/- 0.01). Logistic regression analysis disclosed a positive correlation between the L/M ratio and the presence of gastrointestinal manifestations (p = 0.011). The type of disease (p = 0.28), the disease activity in the JCA patient group (p = 0.24) and NSAID administration (p = 0.210) did not seem to significantly influence the L/M ratio. CONCLUSIONS: All of the subtypes of juvenile chronic arthritides that we studied displayed an increased IP. Hence, gut wall inflammation (albeit asymptomatic) may also be present in o-JIA patients. The SpA-IBD patients with gastrointestinal symptoms displayed the highest mean L/M ratio values. The L/M test seemed to correlate with histopathological features of the gut mucosa. The L/M ratio was shown to be a highly sensitive but poorly specific test for predicting gut inflammatory disease compared to other non-invasive screening tests.

Paediatric reference values for urinary catecholamine metabolites evaluated by high performance liquid chromatography and electrochemical detection.

The majority of the published reference range data on catecholamines excretion by healthy children is incomplete and often contradictory (1). We assayed in the urines of 127 healthy children the values of the catecholamines (norepinephrine, epinephrine, dopamine) and their methylated metabolites (normetanephrine, metanephrine, 3-methoxytyramine) for the determination of paediatric reference ranges. Data were expressed as micrograms/24 h, mumol/24 h and mmol/mol creatinine. An isocratic HPLC procedure by ion-pair reversed phase chromatography on a C18 column, using a single mobile phase containing formic acid, acetonitrile, diethylamine and octane sulphonic acid (ion pairing agent), permitted the separate assay of the various fractions of total catecholamines. The relations between each biogenic amine and age were studied and reference values were determined as a function of age.

Retinol (vitamin A) and retinal-binding protein serum levels in children with cancer at onset.

The aim of the study was to evaluate vitamin A (Vit A) plasma levels in children with newly diagnosed neoplasia (NDN) admitted to the Department of Hematology-Oncology of G. Gaslini Institute. Vit A levels, retinol-binding protein (RBP), and nutritional status were evaluated in 54 children with NDN (22 solid tumors other than neuroblastoma, 16 neuroblastomas, 9 lymphomas, 7 acute lymphoblastic leukemia). Biochemical test results were also compared with those of 47 healthy controls (HC) comparable for sex and age. In children with NDN, mean Vit A plasma level results were 350 micrograms/L (95% CI 288-412); in HC they were 517 micrograms/L (95% CI 471-563), P < 0.001. Mean RBP value results were 3.2 mg/dL (95% CI 2.6-3.9) in NDN and 4.9 mg/dL in HC (95% CI 4.5-5.3), P < 0.001. Fifteen (28%) out of 54 children with NDN were classified as well-nourished, 27/54 (50%) were considered at risk of malnutrition, and 12 (22%) were malnourished. Children with NDN presented reduced Vit A and RBP mean values compared with those of HC. Further studies are needed to better evaluate Vit A metabolism in children with cancer at onset.

MYCN oncogene amplification in neuroblastoma is associated with worse prognosis, except in stage 4s: the Italian experience with 295 children.

PURPOSE: To evaluate the prognostic role of MYCN oncogene amplification in children with neuroblastoma. PATIENTS AND METHODS: Of 694 children (age, 0 to 15 years) with previously untreated neuroblastoma, 295 (42%) were evaluated at diagnosis for MYCN gene amplification. RESULTS: Clinical characteristics and survival results of 295 patients studied and 399 not studied for MYCN were comparable. In 48 of 295 patients studied for MYCN (16%), the gene was amplified (> or = three gene copies). Amplification was more frequent in children older than 1 year, with abdominal tumor (18% v 7%), advanced disease, normal vanillylmandelic (VMA) urinary excretion, and high lactate dehydrogenase (LDH), ferritin, and neuron-specific enolase (NSE) serum levels. In patients studied for MYCN, the 5-year overall survival (OS) rate was higher for children aged less than 1 year (90% v 44%), with extraabdominal tumor, stage 1 or 2 versus 3 versus 4, and normal NSE, LDH, and ferritin serum levels. Patients with amplified MYCN had a worse OS (odds ratio [OR], 3.38; confidence interval [CI], 2.22 to 5.16). This association held after adjustment for other characteristics. The impact of MYCN amplification was greater in patients with favorable characteristics, in particular age (OR, 10.28 for infants; 2.08 for older children) and stage (OR, 35.3 for stage 1 to 2; 8.41 for stage 3; 1.76 for stage 4). However, of 29 children with stage 4s, all three with amplified MYCN survive. In a multivariate analysis, the prognostic role of MYCN amplification, age, and stage was confirmed, but the size of the effect of MYCN was dependent on age and stage. CONCLUSION: MYCN amplification is associated with a worse prognosis in children with neuroblastoma at all ages and stages except 4s. This association is most pronounced in children with otherwise favorable prognostic indicators, and in these children should be considered as an indication for more intensive intervention.

Standard-dose and high-dose peptichemio and cisplatin in children with disseminated poor-risk neuroblastoma: two studies by the Italian Cooperative Group for Neuroblastoma.

PURPOSE: The objective of the present study was to determine whether an increase in the intensity of therapy improves outcome for children with disseminated poor-risk neuroblastoma. PATIENTS AND METHODS: From January 1982 through November 1989, 181 children 1 year or older with newly diagnosed disseminated neuroblastoma were entered onto two consecutive studies of the Italian Cooperative Group for Neuroblastoma (ICGNB): 75 (study NB82) were enrolled from 1982 to 1984 and were treated with standard-dose (SD) chemotherapy, and 106 (study NB85) were enrolled from 1985 to 1989 and received high-dose (HD) chemotherapy. In both treatment protocols, induction therapy included peptichemio and cisplatin (at SD or HD, respectively) and removal of the primary tumor. In study NB82, children who achieved complete or partial tumor regression received SD consolidation therapy, and in study NB85 they received three cycles of HD chemotherapy (3cCT) or one cycle of myeloablative therapy (MAT) followed by autologous bone marrow transplantation (ABMT). RESULTS: Compared with group NB82, the NB85 group had significantly fewer failures (no tumor response or disease progression) after administration of peptichemio (9% v 31%; P < .01), had more complete responses (CRs) and partial responses (PRs) both after treatment with cisplatin (60% v 43%; P = .01) and after surgery (76% v 57%; P < .01), and was more likely to have achieved complete excision of the primary tumor (70% v 46%; P < .01). Overall survival (OS) and progression-free survival (PFS) at 5 years were 11% and 9% in NB82, and 27% and 18% in NB85 (P < .01 for both); however, in NB85, relapses occurred even after 5 years of CR, so that PFS curves converge approximately 7 years after diagnosis. Median survival time was 14 months in NB82 and 24 months in NB85. Children in the NB85 group who after achievement of CR were consolidated with 3cCT had a 5-year PFS of 24% compared with 32% of those treated with MAT followed by ABMT (P = .5). CONCLUSION: Intensified therapy improves response rate and prolongs survival of children with disseminated neuroblastoma, although its impact on the eventual cure rate remains to be established.

Salicylic acid disposition in children with rheumatoid arthritis.

The plasma level profile of SA and SUA after a single oral dose of ASA was studied in 8 children with juvenile rheumatoid arthritis, aged 3.5-15.0 years. Pharmacokinetic parameters were on average similar to those reported in the literature for adult subjects, although a somewhat larger intersubject variability was found.

Falsely elevated urinary level of vanillylmandelic acid induced by griseofulvin.

A 6-year-old girl with mild hepatitis was found to have an elevated urinary level of vanillylmandelic acid (VMA), but no cause for the elevation was found. The patient was receiving griseofulvin for treatment of tinea capitis, and this drug was suspected of causing a falsely elevated urinary VMA level. Four other patients receiving griseofulvin were also found to have elevated urinary VMA levels. In one patient, urinary VMA level determined by an alternate method was normal.