Kinetics of amyloid and prion fibril formation in the absence and presence of dense shell sugar-decorated dendrimers.

The aggregation behavior of the amyloid peptide Aß(1-28) and the prion peptide PrP(185-208) - both responsible for neurodegenerative disorders - was analyzed in the absence and in the presence of poly(propylene imine) (PPI) dendrimers at generation 5 (G5) with a dense shell of maltose and maltotriose units. Thioflavin T (ThT) fluorescence assay and circular dichroism (CD) experiments indicated that fibril formation is enhanced at low dendrimer concentration, while it is prevented at relatively high dendrimer concentrations. Computer aided EPR analysis by means of the selected spin probe 4-octyl-dimethylammonium,2,2,6,6-tetramethyl-piperidine-1-oxyl bromide (CAT8) further demonstrated this behavior, but also provided detailed information on the mechanism of fibril formation and on the different behavior of the differently decorated dendrimers. The CAT8 radicals were progressively trapped at the peptide interphase when peptide aggregates were formed, also monitoring pre-fibrillar structures. At later time, a phase separation of the CAT8 radicals monitors the formation of further supramolecular structures where the probes become squeezed among fibrillar aggregates. The addition of small amounts of dendrimers promotes the formation of peptide fibrils breaking them and providing a larger amount of ends that serve as sites of replications. Conversely, a high amount of dendrimers allows the peptides to well separate from each other such preventing their aggregation. EPR results also indicate that the perturbation played by PPI(G5)-Maltose are more effective onto PrP(185-208) than onto Aß(1-28), while PPI(G5)-Maltotriose is less effective towards PrP(185-208) in both promoting aggregation and preventing it by changing the dendrimer concentration. These results provide useful information about the mechanism and interactions which regulate the ability of macromolecules like the dendrimers to favor, prevent or cure neurodegenerative diseases.

Effect of the disclosure of MS diagnosis on anxiety, mood and quality of life of patients: a prospective study.

BACKGROUND: In the light of the new diagnostic criteria for multiple sclerosis (MS) and currently available early treatment, this study aimed to explore whether, and to what extent, disclosure of the diagnosis of MS or clinically isolated syndrome (CIS) affects patients' anxiety, mood and quality of life (QoL). METHODS: Eligible participants were all patients referred for the first time to the Neurological Unit who had manifested symptoms suggestive of MS for no more than 6 months. All patients were evaluated for (i) QoL (SEIQoL and MS-QoL54), (ii) Anxiety (STAI) and Depression (CMDI) on study inclusion (T0), 30 days after diagnosis disclosure (T30), and after 1 (T1y) and 2 (T2y) years' follow-up. RESULTS: Two hundred and twenty-nine patients were enrolled; 93 of these were unaware of their diagnosis. Patients who already knew their diagnosis (100 with CIS and 22 with MS) were excluded from the main analyses and used to perform control analyses. At the end of the screening, an MS diagnosis was disclosed to 18 of the 93 patients, whereas a CIS diagnosis was disclosed to 62 patients (12 patients received a diagnosis other than MS or CIS). Thirty days after diagnosis disclosure, irrespective of the diagnosis disclosed, both QoL and Anxiety and Depression were significantly rated as better compared to the start of screening, (p(s) < 0.03), and this improvement remained stable over the two annual follow-ups. However, as suggested by a significant 'Time' × 'Diagnosis' interaction with regard to both QoL and Anxiety and Depression (p(s) < 0.02), the effect of the disclosure in the short term differed depending on CIS or MS diagnosis. Specifically, on MSQoL, which is a health-related QoL scale, we found a statically significant improvement, immediately after the diagnosis disclosure, in both the MS and CIS groups (p(s) < 0.01). Differently, on SEIQoL, which is a non health-related QoL measure, and on the anxiety scale, we observed a statistically significant improvement only in the group which received a MS diagnosis (p(s) < 0.03). CONCLUSIONS: This first prospective study provides objective data showing that early disclosure of MS diagnosis improves both the patient's QoL and psychological well-being. In addition, the results seem to suggest that CIS disclosure does not lead to the same favourable effects.

Potencial antioxidante dos extratos de manjericão (Ocimum basilicum Lamiaceae) e orégano (Origanum vulgare Lamiaceae) em óleo de soja / Potential of basil (Ocimum basilicum L. ) and oregano (Origanum vulgare L. ) extracts as antioxidant to soybean oil

O presente trabalho teve como objetivos avaliar o potencial antioxidante dos extratos de manjericão (Ocimum basilicum L.) e orégano (Origanum vulgare L.), e medir a estabilidade oxidativa do óleo de soja adicionado de ambos os extratos. Foram obtidos extratos de manjericão e orégano nas formas in natura e seco, a partir das folhas das especiarias submetidas às extrações aquosas, etanólicas e sequenciais por 30 min, na proporção de 1:3 (m/m, especiaria:solvente), sob agitação contínua e temperatura ambiente. Nos extratos foram determinados o valor de concentração eficiente (CE50), a atividade antioxidante máxima (AA) e a quantidade de compostos fenólicos totais (CFT). Os extratos de orégano e manjericão com maior atividade antioxidante foram aplicados no óleo de soja em concentrações que variaram de 250 a 2.000 mg kg-1, para avaliação da estabilidade oxidativa. Os resultados indicaram que os extratos etanólicos de manjericão in natura com CE50 = 863,97 µg mL-1, AA = 35,63% e CFT = 56,55 mg g-1 e orégano seco com CE50 = 415,82 µg mL-1, AA = 48,42% e CFT = 147,96 mg g-1 foram os mais eficientes para serem aplicados ao óleo de soja na concentração de 2.000 mg kg-1, na qual apresentaram a maior estabilidade oxidativa, 21,8 e 15,1 horas, respectivamente. Com base na metodologia empregada e dentro das condições estudadas, concluiu-se que os extratos etanólicos de manjericão in natura e orégano seco revelaram potencial antioxidante quando aplicados em óleo de soja.

This study aimed to evaluate the antioxidant potential of basil (Ocimum basilicum L.) and oregano (Origanum vulgare L.) extracts and to measure the oxidative stability of soybean oil added to both extracts. Basil and oregano extracts were obtained in fresh and dry forms from the leaves of spices subjected to aqueous, ethanol and sequential extraction for 30 min at a ratio of 1:3 (m/m, spice:solvent) and continuously shaken at room temperature. For the extracts, the value of effective concentration (EC50), the maximum antioxidant activity (AA) and the amount of total phenolic compounds (TFC) were obtained. The oregano and basil extracts that had higher antioxidant activity were applied to soybean oil at concentrations ranging from 250 to 2,000 mg kg-1, to evaluate the oxidative stability. The results indicated that the ethanol extracts of fresh basil with EC50 = 863.97 mg mL-1, AA = 35.63% and TFC = 56.55 mg g-1 and dry oregano with EC50 = 415.82 mg mL-1, AA = 48.42% and TFC = 147.96 mg g-1 were more efficient for application in soybean oil at a concentration of 2,000 mg kg-1, which showed the highest oxidative stability, 21.8 and 15.1 hours, respectively. Based on the employed methodology and under the studied conditions, it was concluded that the ethanol extracts of fresh basil and dry oregano showed antioxidant potential when applied in soybean oil.

Risk index for peri-operative atrial fibrillation in patients undergoing open intracranial neurosurgical procedures.

The aim of this prospective study was to determine the prevalence of pre-operative atrial fibrillation and the incidence of postoperative atrial fibrillation in patients undergoing elective or emergency intracranial neurosurgical procedures and the relation to survival and neurological outcome at 6-months follow-up compared to patients with sinus rhythm. A total of 2020 patients were enrolled; 1540 patients underwent elective procedures and 480 underwent emergency procedures. Prevalence of pre-operative atrial fibrillation was 3.7% in elective and 7.2% in emergency procedures (p = 0.0012). In patients undergoing elective cerebral procedures with pre-operative atrial fibrillation, compared to patients with sinus rhythm, 6-month neurological outcome and survival rate are similar. In patients undergoing emergency neurosurgical cerebral procedures, the presence of pre-operative atrial fibrillation is related to an increased risk of poor neurological outcome but with similar survival rate.

Cardiovascular effects of intravenous propofol administered at two infusion rates: a transthoracic echocardiographic study.

We assessed the haemodynamic changes after a propofol infusion at two rates in low-risk unpremedicated patients (ASA I-II). To determine contractility changes and loading conditions, we measured the ejection fraction, end-systolic quotient and fractional shortening on transthoracic echocardiograms. We studied 40 patients undergoing peripheral neurosurgical procedures under general anaesthesia induced by propofol alone (total dose 2.5 mg.kg-1). Patients were randomly assigned to receive propofol at an infusion rate of 10 mg.s-1; or 2 mg.s-1. Haemodynamic data were recorded simultaneously immediately before propofol infusion, at the end of infusion, and 5 and 10 min after the infusion ended. The higher infusion rate induced a larger decrease in mean arterial pressure than the lower infusion rate (- 20% vs. - 10% from baseline, p = 0.01). In both groups, global and segmental ventricular function remained unchanged throughout the study. In both groups, there were markedly reduced end-systolic quotients--presumably related to diminished afterload, and in the higher infusion-rate group a significant reduction in fractional shortening--presumably related principally to diminished preload.

Ultrasound echo-enhancers in the evaluation of endovascular prostheses.

Whereas conventional vascular surgical procedures are routinely monitored by ultrasound imaging, endovascular prostheses are usually monitored by radiographical imaging techniques. The aim of this study was to determine the safety, patient acceptance and role of ultrasound echo-enhancers (SHU 508 A) in the evaluation of endovascular devices. Nine patients were studied: six had stents (four in the internal carotid artery and two in the renal artery) and three had endoluminal prostheses (one in the abdominal aorta, one in the subclavian and one in the iliac artery). Endovascular patency and correct placement were studied with contrast angiography and ultrasound examination with and without contrast enhancement. Patients underwent angiography at the end of the endovascular procedure, and ultrasound examinations on the first postoperative day. Ultrasound contrast media (SHU 508 A) was injected through an antecubital vein at a rate of 1 ml/s. A total of 13 injections were given in nine patients. Ultrasonograms were obtained with 7.5 and 3.5 MHz transducers (Acuson 128 XP) and recorded on videotape for off-line visual inspection. Baseline and echo-enhanced sequences were assessed by two independent observers. None of the patients reported side-effects during or after the injection of the ultrasound echo-enhancer. Postoperative angiography showed endovascular patency and correct placement in all patients. The baseline ultrasound examination confirmed endoprosthesis patency in seven of nine patients: none revealed endoprosthesis malplacement. Contrast-enhanced ultrasound examination confirmed endoprosthesis patency. In two cases, the echo-contrast examination revealed persisting flow within the aneurysmal sac: in another patient it showed the incomplete adhesion of the distal portion of the endoprosthesis to the arterial wall. The preliminary findings suggest that ultrasound echo-enhancers are safe to use and induce no side-effects. Echo-enhanced sequences often provide additional information on the technical success of endovascular procedures. They promise to be useful in follow-up studies for assessing the functioning of endoprostheses.

Pulmonary transit of sonicated albumin microbubbles during controlled mechanical ventilation: a transthoracic echocardiographic study.

UNLABELLED: Air-filled human serum albumin microspheres are ultrasonic contrast tracers that pass through the right ventricle, traverse the lungs, and effectively opacify the left heart chambers in spontaneously breathing patients. In this clinical study, we assessed whether they also do so in anesthetized patients during and after mechanical ventilation. In 20 anesthetized patients undergoing intermittent positive pressure ventilation (IPPV) for elective peripheral neurosurgical procedures, a sonicated ultrasound contrast drug (0.06 mL/kg) was injected i.v. before inducing anesthesia in spontaneously breathing patients (baseline), during IPPV, and 5 and 30 min after tracheal extubation. Transthoracic echocardiograms were obtained in the four-chamber apical view and were recorded for off-line analysis. Time to contrast appearance in the right ventricle and pulmonary transit time were measured in cardiac cycles. The peak intensity of right and left ventricular chamber opacification were scored on a scale ranging from 1 (no contrast or traces only) to 5 (attenuation). After each injection, the time for contrast appearance in the right ventricle was similar in all patients. Pulmonary transit time increased significantly during IPPV and was normal 5 min and 30 min after extubation. Right ventricular chamber opacification achieved high-grade intensity and remained constant before, during, and after IPPV. Conversely, although the baseline contrast injection resulted in high-grade left ventricular chamber opacification, the intensity decreased significantly during IPPV, remained low 5 min after extubation, and was normalized 30 min after extubation. IMPLICATIONS: During intermittent positive pressure ventilation, i.v. sonicated albumin microbubbles pass through the lungs poorly and inefficiently opacify the left ventricle compared with the effects observed during spontaneous ventilation.

Self-aligning lidar for the continuous monitoring of the atmosphere.

In a lidar system an accurate transmitter-receiver alignment is essential for correct results. Usually this optical adjustment is time consuming and requires the intervention of highly qualified personnel. As a solution to this problem, a fast and precise automatic alignment procedure is presented, based on a simple model of the transmitter-receiver overlap. The lidar mounted at the Naples University is used to test this method. A centering precision of few microradians is obtained through dedicated software controlling a gimbal-mounted mirror. The automatic alignment procedure is then assessed. In particular, the correctness of the center and of its error is determined. Finally, the system is applied to the monitoring of tropospheric aerosols, leading to the continuous retrieval of profiles with fine spatiotemporal resolution.

Analysis of the receiver response in lidar measurements.

We report on the calculation of the effective telescope area in lidar applications by a ray-tracing approach. This method allows one to consider the true experimental working conditions and hence to obtain accurate values of the effective telescope area as a function of the height. This in turn allows the retrieval of the signal from the ranges where the overlap function is not constant (e.g., lower ranges), thus increasing the useful range interval. Moreover, we show that the spherical mirrors are more appropriate than the parabolic ones for most of the lidar measurements, although a particular alignment procedure, such as the one we describe, must be used.

Measurement of the lidar signal fluctuation with a shot-per-shot instrument.

A measurement of the signal noise was carried out with a shot-per-shot lidar. This system was operated in the UV spectral region for ozone profiling in the low troposphere. We report on important discrepancies between our results and the estimations based on the assumptions commonly supporting the numerical modeling of lidar experiments.

Variables associated with hospital arrival time after stroke: effect of delay on the clinical efficiency of early treatment.

BACKGROUND AND PURPOSE: A limiting criterion for the eligibility of patients in clinical trials investigating acute stroke therapies is that time between onset of symptoms and arrival in the hospital should fall within the "therapeutic window." The aims of this study were to estimate hospital arrival time in an unselected sample of stroke patients, to assess the association with some clinical and demographic variables, and to evaluate the effects of the delay on the clinical efficiency of an effective treatment. METHODS: We evaluated the delay in hospital arrival time in 189 patients (84 men, 105 women; mean age, 76.5 years) prospectively collected in the S Orsola-Malpighi Community Teaching Hospital in Bologna, Italy. Cutoffs of 2 and 5 hours were chosen to allow for hypothetical treatment within 3 and 6 hours, respectively. Exact multiple logistic regression was used to predict the delay as a function of dichotomized age, sex, symptoms on awakening, day of the week, hour of the day, area of residence, level of consciousness, and level of motor power defect. We then projected the effectiveness of tissue plasminogen activator (TPA) on disability as estimated with the aid of the odds ratio from the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial onto our unselected sample to evaluate clinical efficiency of treatment as a function of arrival time and of hypothetical effects of educational efforts to reduce it. RESULTS: The mean interval between onset of symptoms and hospital arrival was 680 minutes; 59 patients (31%) arrived within 2 hours and 100 (53%) within 5 hours. Onset of symptoms when awake, drowsiness or coma, and paralysis of at least one limb were the only independent predictors of hospital arrival within 2 and 5 hours in both the total sample and the subgroup of patients who were awake at stroke onset. The effectiveness of 17%, extrapolated with the aid of the odds ratio of 1.6 of having a favorable outcome (Barthel Index > or = 95 at 3 months) in treated versus untreated patients in the NINDS rt-PA Stroke Trial, corresponded to a projected clinical efficiency of 5%. This could be doubled by hypothesizing a 100% effect of educational efforts in reducing the delay in hospital arrival time. CONCLUSIONS: Patients with milder symptoms, for whom treatment might be more effective, were less likely to arrive in time for therapy. The proposed model of the relationship between the delay in hospital presentation after a stroke and the clinical efficiency of a given treatment might be useful for planning future clinical trials on early stroke treatment and predicting the impact of an educational program aimed at shortening arrival time.

Correction scheme for experimental biases in differential absorption lidar tropospheric ozone measurements based on the analysis of shot per shot data samples.

From lidar signals detected with a shot per shot differential absorption lidar instrument tuned for tropospheric ozone measurements and recording each individual return, we reconstruct histograms of their sampled values for each channel of our digitizers. The analysis of their shape permits the correction of our measurements for experimental biases. In particular, a negative correlation is found between the skew of the histograms and the intensity of the backscattered light. The skew comes from a tail at high sampled values, interpreted as due to a raise of the relative contribution to the signal of a signal-induced noise when this intensity diminishes. By fitting a Gaussian function to the histograms without considering their tails, we calculate average signals unbiased by the corresponding noise. This approach allows us to increase the range of our ozone profiles, up to as much as double it in some cases.

Mortality from primary malignant brain tumors in the Province of Bologna, Italy, 1986-1988.

INTRODUCTION: We performed a study of mortality from primary malignant brain tumors (PMBT) in the province of Bologna, Italy, during the years 1986 to 1988. MATERIALS AND METHODS: The study was based on death certificates from the Cancer Registry of the province of Bologna. We verified death certificates for both false-positive and false-negative cases. RESULTS: The crude mortality rate was 6.7/100,000 population per year. The age and sex-adjusted mortality rate, standardized to the Italian population (Italy 81), was 5.34/100,000 (95% CI = 3.9 to 6.7). CONCLUSION: Our figures are higher than those previously reported in Italy, but are similar to values of incidence and mortality found in northern Europe and in North America.

Fever in acute stroke worsens prognosis. A prospective study.

BACKGROUND AND PURPOSE: No definitive data are yet available on the effects of body temperature on neurological damage after cerebral ischemia in humans. Experimental animal models have provided much evidence, but to our knowledge, only two studies on the relationship between fever and prognosis of stroke in humans have been published. The aim of our study was to investigate the prognostic role of fever in the first 7 days of hospitalization in a cohort of patients admitted to our hospital for acute stroke. METHODS: We analyzed the data of 183 patients included in a prospective observational prognostic study. Vital status at 30 days was considered the main outcome and was obtained for all patients. Age, level of consciousness, and glycemia at the time of hospitalization were considered covariates for an exact logistic regression analysis. The maximum temperature recorded during the first 7 days dichotomized as "no or low fever" versus "high fever" was added to the model. Death within 10 days, taken as a secondary outcome suggestive of death from neurological causes, was analyzed with exact permutation tests. RESULTS: Of the 183 patients analyzed in this study, 43% had fever during the first 7 days after hospitalization. The mean value of the maximum temperature recorded during the first 7 days in the 78 febrile patients was 38.3 degrees C, and the median was 37.9 degrees C. Onset of fever occurred in only 15% of febrile patients during the first day and in 49% on the second. The prognostic roles of age, level of consciousness, and glycemia were confirmed by exact logistic regression. Degree of consciousness impairment was the strongest prognostic variable, with an odds ratio (OR) of 11.4 (95% confidence interval [CI], 4.4 to 31.6). High fever (maximum temperature recorded during the first 7 days > or = 37.9 degrees C) was an independent factor for a worse prognosis, with an OR of 3.4 (95% CI, 1.2 to 9.5). The OR of dying within 10 days versus dying between 11 and 30 days was 4.9 (95% CI, 1.2 to 25.2) in patients with high fever with respect to all other patients. CONCLUSIONS: Fever in the first 7 days was an independent predictor of poor outcome during the first month after a stroke. No data were available on the underlying causes of fever, but the higher risk of death in the first 10 days, most frequently attributed to neurological mechanisms, suggested that high temperature was an independent component of poor prognosis and not only an epiphenomenon of other complications in the course after a stroke. In agreement with animal studies, we found that patients with higher temperature had a worse stroke outcome.

Brain MRI and SPET in thrombotic thrombocytopenic purpura.

We describe 5 cases of thrombotic thrombocytopenic purpura (TTP) with neurological manifestations. All of the patients underwent brain magnetic resonance imaging (MRI) following recovery; two underwent single photon emission tomography (SPET) during the acute phase of the disease. SPET showed reduced cerebral blood flow, whereas the results of brain MRI were normal in all patients. Plasma exchange (PE) treatment was promptly instituted in all cases. Our findings show that prompt treatment with PE may avoid permanent brain damage even when the neurological signs and symptoms are relate to brain ischemia.

Left ventricular-coronary sinus fistula after mitral valve replacement: diagnosis by transthoracic and transesophageal echocardiography.

Repeated mitral valve replacement, particularly in case of heavily calcified mitral annulus, may lead to iatrogenic injury to the posterior atrioventricular groove leading to hematoma, myocardial rupture and/or intracardiac shunt. In this report, the echocardiographic features of left ventricular to coronary sinus fistula developed after repeated mitral valve replacement, are described for the first time. Transthoracic and transesophageal echocardiography allow the early detection of this extremely rare form of iatrogenic injury.

Incidence of stroke among inpatients in a large Italian hospital.

BACKGROUND AND PURPOSE: The incidence of stroke among inpatients is not known. The aim of our study was to investigate the incidence of stroke not preceded by evident iatrogenic factors such as surgical or medical procedures in a cohort of inpatients in a large Italian general hospital. METHODS: From January 1, 1992, to December 31, 1992, we evaluated patients referred to our neurology department with a suspected diagnosis of stroke that occurred during hospitalization. Patients presenting with stroke as a complication of iatrogenic causes were excluded. We calculated the incidence rate of first-ever stroke in our cohort (crude and among patients aged older than 50 years), thereafter adjusting these rates for age to the general population of the city district of Bologna (Italy). RESULTS: In 1992, 22 inpatients had a first-ever stroke with no evidence of iatrogenic factors. The crude stroke incidence rate was 11.08/1000 per year (95% confidence interval, 6.95 to 16.73). The age-adjusted rate was 5.46 (95% confidence interval 3.42 to 8.24). CONCLUSIONS: The incidence rate of first-ever stroke among hospitalized patients is higher than those reported in community-based studies. Higher frequency of coronary artery disease among our patients could explain our findings. Further studies are needed to identify possible predisposing factors (individual or environmental) for stroke among inpatients.

Interobserver variability in CT assessment of brain atrophy.

To assess interobserver variability in estimation of brain atrophy based on CT, four neuroradiologists examined CT brain images of 150 consecutive patients without focal lesions. An independent neuroradiologist made the following quantitative measurements: frontal horn index, subarachnoid space area and the ratio between subarachnoid space area and inner skull space area. Level of agreement was fair for the presence (k = 0.24), slight for the degree (mild, moderate, severe) (k = 0.24) and moderate for the type (cortical, subcortical, mixed) of atrophy (k = 0.59). There was a highly significant correlation between the number of observers agreeing and quantitative measurements. We concluded that neuroradiologists' subjective estimation of brain atrophy alone is not reliable. Quantitative measurements would be needed in cases where the presence of brain atrophy might determine clinical decisions.