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Biomedical subjects

M Brambilla

Publications and source records attributed to M Brambilla.

At least 19 recordsLinked to original sources

Distinct roles for PAR1- and PAR2-mediated vasomotor modulation in human arterial and venous conduits.

BACKGROUND: Patency rates after coronary artery bypass grafting (CABG) are better if the internal mammary artery (IMA) is used rather than the greater saphenous vein (GSV), and may be related to the endothelial release of vasodilators antagonizing vascular contraction. It has recently been shown that a family of protease-activated receptors (PARs) modulate endothelium-dependent vasodilatation. OBJECTIVE AND METHODS: The aim of this study was to evaluate the presence and functional role of protease-activated receptor 1 (PAR1) and protease-activated receptor 2 (PAR2) in mediating vascular tone in IMAs and GSVs from patients undergoing CABG by means of real time-PCR and isometric tension measurements. RESULTS: PAR1 mRNA levels were higher than those of PAR2 mRNA in both vessels. A selective PAR2-activating peptide (PAR2-AP), SLIGKV-NH(2) (0.01-100 micromol L(-1)), failed to induce vasorelaxation in precontracted IMA and GSV rings, whereas the selective PAR1-AP, TFLLR-NH(2) (0.001 to 10 micromol L(-1)), caused greater endothelium-dependent relaxation in the IMAs (pD(2) values 7.25 +/- 0.6 vs. 7.86 +/- 0.42, P < 0.05; E(max) values 56.2 +/- 17.3% vs. 29.7 +/- 13.4%, P < 0.001). Preincubation with TNFalpha (3 nmol L(-1)) induced vasorelaxation in IMAs in response to PAR2-AP (P < 0.05 vs. non-stimulated vessels); the response to PAR1-AP was unchanged. The relaxation induced by both PAR-APs was NO- and endothelium-dependent. CONCLUSION: These data show that functionally active PAR1 and PAR2 are present in IMAs and GSVs, and that inflammatory stimuli selectively enhance endothelium-dependent relaxation to PAR2-AP in IMAs.

Adult↗

Neutron production from a mobile linear accelerator operating in electron mode for intraoperative radiation therapy.

Intraoperative electron beam radiotherapy is increasingly performed using mobile linac delivering therapeutic radiation doses in unshielded operating rooms. While no special neutron-shielding problem should arise for operation at 10 MeV or less, it is not clear whether this holds true for operation at higher energies. This paper reports the measured neutron production from a Mobetron mobile electron linac, operated at 12 MeV, and compares the results with those from a conventional linac, also operated at 12 MeV in electron mode. Neutron leakage measurements were performed by means of passive bubble detectors in the scattering foil, patient and floor planes. Neutron dose equivalent rates per unit of electron dose delivered by the Mobetron at its normal treatment distance (50 cm SSD) were 0.33 microSv Gy(-1) at the accelerator head, 0.18 microSv Gy(-1) in the patient plane at 15 cm from the beam axis and 0.31 microSv Gy(-1) at the floor plane, on the beam axis and under the beam stopper. For a weekly workload of 250 Gy, the weekly neutron dose equivalents at 12 MeV for the Mobetron at a distance of 300 cm from the scattering foil were 14.3 and 1.7 microSv/week for floor below and adjoining areas on the same floor, respectively. Neutron dose equivalent rates generated from Mobetron are at least one order of magnitude lower than ones produced by a conventional linac operated at the same energy in electron mode. Mobetron can be used at 12 MeV in an unshielded operating room for a weekly workload of up to 250 Gy if the bremsstrahlung x-rays are shielded to negligible levels.

Combined Modality Therapy↗

Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation.

BACKGROUND: Blood-borne tissue factor (TF) plays a crucial role in thrombogenesis. AIM: To study whether polymorphonuclear leukocytes (PMN) are a source of TF. METHODS AND RESULTS: Human PMN were carefully separated from other blood cells and stimulated for 3 min with purified P-selectin or the chemotactic peptide formyl-MetLeuPhe (fMLP): they expressed both TF procoagulant activity, as identified by specific TF MoAb and inactivated factor VIIa blockade; and TF:Ag (four to six times), as shown by flow-cytometry and immunocytochemistry. About 40% of permeabilized PMN, both resting and stimulated, contained TF:Ag, indicating that stimulation only modifies the location of TF:Ag within PMN. By real time-polymerase chain reaction (RT-PCR), a very low amount of TF mRNA was detectable in resting PMN, but a 3- to 5-fold increase was observed after 1-h stimulation with P-selectin or fMLP, respectively. CONCLUSIONS: These findings suggest that TF is not constitutively expressed in peripheral PMN, but can be up-regulated and produced upon stimulation and specific gene transcription, as for instance during contact with activated platelets or endothelium. The stored TF is rapidly expressed in vitro as a functional molecule on the surface of activated PMN. The availability of PMN TF supports the relevance of inflammatory cells and their interaction with platelets for fibrin deposition and thrombus formation.

Antibodies, Monoclonal↗

Microprocessor-controlled optical stimulating device to improve the gait of patients with Parkinson's disease.

Different types of visual cue for subjects with Parkinson's disease (PD) produced an improvement in gait and helped some of them prevent or overcome freezing episodes. The paper describes a portable gait-enabling device (optical stimulating glasses (OSGs) that provides, in the peripheral field of view, different types of continuous optic flow (backward or forward) and intermittent stimuli synchronised with external events. The OSGs are a programmable, stand-alone, augmented reality system that can be interfaced with a PC for program set-up. It consists of a pair of non-corrective glasses, equipped with two matrixes of 70 micro light emitting diodes, one on each side, controlled by a microprocessor. Two foot-switches are used to synchronise optical stimulation with specific gait events. A pilot study was carried out on three PD patients and three controls, with different types of optic flow during walking along a fixed path. The continuous optic flow in the forward direction produced an increase in gait velocity in the PD patients (up to + 11% in average), whereas the controls had small variations. The stimulation synchronised with the swing phase, associated with an attentional strategy, produced a remarkable increase in stride length for all subjects. After prolonged testing, the device has shown good applicability and technical functionality, it is easily wearable and transportable, and it does not interfere with gait.

Aged↗

Evaluation of a model for leaf to fruit transfer of radionuclides in processing tomato plants using an independent set of data.

Because of their varied possibilities of consumption, tomatoes are an important component of the human diet. This paper presents results of the evaluation of a dynamic model (Ventomod) for the short-term behaviour of radionuclides deposited on tomato plants following a direct contamination event. To check its forecasting capability in assessing the risk of radionuclide contamination of the human diet, it has been tested with an independent dataset on the leaf to fruit transfer of 134Cs in a typical Hungarian tomato variety, "Dwarf of Kecskemet". Data obtained from this pot experiment were used to evaluate model behaviour. Model constants were varied according to the differences between the Hungarian dataset and the one used to calibrate it. Results show that the model output well reproduces the observed activity of fruits for various levels of contamination and at different contamination dates. The main part of this report summarises the experimental protocol, compares the experimental results with model predictions generated by Ventomod and makes recommendations for both updating model parameters and undertaking further experimental work.

Agriculture↗

Foliar uptake of 134Cs and 85Sr in strawberry as function by leaf age.

In this paper a study of the foliar uptake and translocation of 134Cs and 85Sr in a herbaceous fruit plant is presented. In particular, absorption, translocation and loss of these radionuclides in strawberry plants have been studied in relation to the age of contaminated leaves. Strawberry plants were contaminated by distributing droplets of an aqueous solution containing 134CsCl and 85SrCl2 on the surface of two leaves per plant. One half of the plants was contaminated through two young leaves, a second half through two old leaves. Sets of plants were collected 1 day, 7 days and 15 days after contamination. One half of them was rinsed with double distilled water before gamma analysis. Rinsing contaminated leaves removes on average 55% of the applied 134Cs and 45% of 85Sr. The activity removed decreases during the 15 days of the experimental study, both for 134Cs and for 85Sr, suggesting an increase in foliar absorption during this period. The activity removed does not differ between old and young leaves. "External loss" is lower for young than old contaminated leaves. "Internal loss" through translocation occurs mainly for 134Cs. Translocation coefficients from contaminated leaves to fruits are two orders of magnitude higher for 134Cs (4.0%), than for 85Sr (0.05%). Leaf to fruit translocation coefficients for 134Cs are higher from young leaves (5.8%), than from old leaves (2.3%).

Cesium Radioisotopes↗

Chronic pain as expression of neural substrates. Issues from the neuronal dynamics and mutual relations.

The Thalamo-Cortical somatosensory loop shows important synaptic re-organization in cases of chronic pain. Animal models exhibit severe functional distortions, potentially related to the anatomic rearrangements. Connectivity and information theoretic measurement represent important tools to quantify the functional disarrays. We performed electrophysiological experiments with multisite, multielectrode simultaneous recordings in the Thalamus and in the Somatosensory Cortex. The recurrent anomalies in the analytic estimates induce to hypothesize a potential neurodynamical explanation of the sensory context.

Action Potentials↗

Ventomod: a dynamic model for leaf to fruit transfer of radionuclides in processing tomato plants (Lycopersicon esculentum Mill.) following a direct contamination event.

This paper presents results on the calibration and validation of a model (Ventomod) for leaf to fruit transfer of (134)Cs, (85)Sr and (65)Zn in processing tomato plants after leaf contamination. Several models (e.g. FARMLAND) that deal specifically with the transfer of radionuclides to fruits are adaptations of models that were developed for agricultural crops such as leafy green vegetables. "Ventomod" represents a dynamic evaluation model exclusively built for the short-term behaviour of radionuclide depositions. It forecasts the level of radionuclide contamination in ripe processing tomato fruits following an accidental radionuclide release into the atmosphere. A validation of the developed model by data sets from an independent experiment showed that the model successfully reproduced the observed radionuclide distribution and dynamics in tomato fruits. The level of uncertainty was within the normal range of similar assessment models. For a more general use of this model further testing with independent data sets from experiments obtained under different environmental conditions and data from other horticulturally important plant species would be desirable.

Agriculture↗

Foliar and root uptake of 134Cs, 85Sr and 65Zn in processing tomato plants (Lycopersicon esculentum Mill.).

The results of an experimental study on the behaviour of 134Cs, 85Sr and 65Zn in processing tomato plants grown in peat substrate are presented. Plants were contaminated by wet deposition of 134Cs, 85Sr and 65Zn, either by sprinkling the above ground part at two phenological stages or by administering 134Cs, 85Sr and 65Zn to the soil. The plants contaminated at the second phenological stage intercepted 38.3% less than those contaminated at the first stage, although leaf area increased by more than double. Transfer coefficients from peat soil to ripe fruit for 134Cs are significantly higher than those for 85Sr and 65Zn. Leaf to fruit transfer coefficients for 134Cs are one order of magnitude higher than for 65Zn and two orders higher than for 85Sr. Only when deposition affects fruits, as at the second phenological stage, are transfer coefficients to fruits similar for the three radionuclides.

Absorption↗

15-deoxy-delta12,14-Prostaglandin J2 inhibits tissue factor expression in human macrophages and endothelial cells: evidence for ERK1/2 signaling pathway blockade.

Basic and clinical evidence has provided insight into the molecular events that link inflammation and coagulation. Increased expression of tissue factor (TF) by circulating and vascular cells has been indicated as responsible for the thrombotic complications associated with acute and chronic inflammation. TF is indeed inducible in circulating and vascular cells by cytokines and bacterial lipopolysaccharide (LPS) and its expression triggers the coagulation. The cyclopentenone prostaglandins are naturally occurring prostaglandin D2 (PGD2) derivatives that comprises prostaglandin J2 (PGJ2) and its metabolites delta12-PGJ2 and 15-deoxy- delta12,14-prostaglandin J2 (15d-PGJ2). These compounds, detected in vivo in a later phase of the inflammatory response, are characterized by anti-inflammatory activity and participate to the resolution of inflammation. We have here investigated the effect of 15d-PGJ2 on TF expression in human macrophages and endothelial cells (HUVEC). Our results indicate that 15d-PGJ2 down-regulates LPS- and TNFalpha-induced TF activity, protein and mRNA through inhibition of TF gene transcription. The effect of 15d-PGJ2 is targeted to the NF-kappaB/I-kappaB pathway and to the mitogen activated protein kinase ERK1/2. A role of PPAR-gamma activation in TF inhibition by 15d-PGJ2 was excluded. We conclude that 15d-PGJ2 negatively affects TF expression in macrophages and endothelial cells through a PPARgamma-independent mechanism. This down-regulation may be crucial to limit excessive blood clotting activation in immuno-inflammatory diseases.

Down-Regulation↗

Two-photon cavity solitons in active optical media.

We show that broad-area cascade lasers with no absorbing intracavity elements support the spontaneous formation of two-dimensional bright localized structures in a dark background. These cavity solitons consist of islands of two-photon emission embedded in a background of single-photon emission. We discuss the mechanisms through which these structures are formed and interact, along with their properties and stability.

Journal Article↗

Cavity solitons in semiconductor microresonators: existence, stability, and dynamical properties

We apply a versatile numerical technique to establishing the existence of cavity solitons (CS) in a semiconductor microresonator with bulk GaAs or multiple quantum well GaAs/AlGaAs as its active layer. Based on a Newton method, our approach implies the evaluation of the linearized operator describing deviations from the exact stationary state. The eigenvalues of this operator determine the dynamical stability of the CS. A typical eigenspectrum contains a zero eigenvalue with which a "neutral mode" of the CS is associated. Such neutral modes are characteristic of models with translational symmetry. All other eigenvalues typically have negative real parts large enough to cause any excitations to die out in a few medium response times. The neutral mode thus dominates the response to external random or deterministic perturbations, and its excitation induces a simple translation of the CS, which are thus stable and robust. We show how to relate the speed with which a CS moves under external perturbations to the projection of the perturbations on to the neutral mode, and give some examples, including weak gradients on the driving field and interaction with other CS. Finally, we show that the separatrix between two stable coexisting solutions: the homogeneous solution and the CS is the intervening unstable CS solution. Our results are important with a view to future applications of CS to optical information processing.

Journal Article↗

[Clocking diagnostic and therapeutic procedures in coronary care unit patients: analysis of clinical performance times].

BACKGROUND: An optimal use and exploitation of professional personnel is of paramount importance for health management organizations, as human resources are both their greatest asset and heaviest financial burden. To better understand the amount of medic and paramedic work and time required for the typical diagnostic and therapeutic procedures in a coronary-care unit setting, we measured their average times and analyzed their inherent co-factors. METHODS: This study was conducted on 206 consecutive coronary-care unit patients. These patients were divided into subgroups according to their admission diagnosis: acute myocardial infarction, unstable angina, acute cardiac failure, pulmonary embolism or other pathologies. Each subgroup was then subdivided even further according to the severity of their clinical status. Diagnostic and therapeutic procedures ("macroactivities") have been identified and each one was subdivided into sub-procedures ("microactivities"). All microactivities were carefully clocked in every patient in order to calculate the average execution time for every macroactivity. RESULTS: Our data show that myocardial infarction patients and, in general, a more severe clinical status required a longer stay in the coronary-care unit. Again, longer overall clinical performance times were necessary in myocardial infarction patients as compared to the unstable angina subgroup. There were no statistically significant differences among other subgroups. More severely ill patients required longer clinical performance times because of both a longer coronary-care unit stay and longer clinical performance time per day. More than half of the total clinical performance time for each patient was spent during the first two days. Paramedics supplied more than 80% of the total performance time. CONCLUSIONS: The authors undertook a study of typical coronary-care unit clinical activities by clocking the performance times of the usual diagnostic and therapeutic procedures. The data thus obtained come from direct measurements and describe the clinical performance of both medics and paramedics in a real-life setting. This could thus be used as a yardstick to verify current workload standards. It is hoped that a deeper understanding of these activities will optimize the full exploitation of available human resources.

Adult↗

Detection of moderate and severe coronary artery stenosis with technetium-99m tetrofosmin myocardial single-photon emission tomography.

The aim of this study was to determine the diagnostic accuracy of technetium-99m tetrofosmin myocardial imaging for the localization of coronary artery stenoses of different degrees of severity. Stress-rest single-photon emission tomography (SPET) was performed on separate days in 80 patients (64 males, 16 females; mean age 61 years; 43 patients with previous myocardial infarction; 18 patients with pharmacological stress), within 6 months of coronary angiography. Scintigraphic images were blindly and independently evaluated by three observers. Coronary stenosis was defined as a >50% narrowing in luminal diameter; severe stenosis was defined as a proximal stenosis of >75% or a peripheral stenosis of >90%. Coronary angiography revealed normal coronary arteries or insignificant coronary stenosis in 13 patients and significant coronary stenoses in 67 patients. The sensitivity and specificity of 99mTc-tetrofosmin SPET in respect of severely stenosed vessels were, respectively, 80% and 65% for the left anterior descending artery (LAD), 100% and 46% for the right coronary artery (RCA) and 58 and 78% for the left circumflex artery (LCx) territories. Considering all the significantly stenosed vessels, a significant decrease in sensitivity was observed for LAD territories (to 59%, P=0.05), and a nonsignificant decrease for RCA (88%) and LCx (47%) territories while specificity values remained essentially unchanged. No significant changes in sensitivity or specificity were observed when regions with previous myocardial infarction were excluded. In conclusion, the sensitivity of 99mTc-tetrofosmin SPET for the localization of individual stenosed vessels is only moderate when all significant stenoses are considered, but the ability of this technique to predict the location of severe coronary artery stenoses seems satisfactory, with the exception of the low specificity in respect of RCA territories.

Coronary Angiography↗

Feasibility of a rapid method to evaluate platelet survival time.

UNLABELLED: The purpose of this study was to evaluate the feasibility of a shorter method of performing platelet kinetic studies with respect to the conventional 8-9-day approach. METHODS: We studied 41 patients (28 women, 13 men; mean age 52 yr) with primary idiopathic thombocytopenic purpura (ITP) (n = 20), secondary ITP (n = 9), HCV associated thrombocytopenia (n = 9), splenectomy (n = 1) and hairy-cell leukemia (n = 1). The patients were in a steady-state of platelet turnover. Initial platelet counts ranged from 19 to 302 x 10(9)/liter (mean value = 83). Platelet survival times (PST) were measured from the blood radioactivity disappearance curve of 111In-oxine-labeled autologus platelets following the recommendations of the International Committee for Standardization in Haematology: blood samples were taken at 30 min and 2 and 4 hr and thereafter daily for 7 days. PST was calculated by the weighted mean method and ranged from 18 to 219 hr (mean value = 98). PST was also calculated using only the data collected at 2, 48 and 96 hr. If the radioactivity in the blood at 96 hr exceeded 10% of the 2-hr value, the additional point at 168 hr was used. RESULTS: By using this reduced dataset, we obtained a correlation of r = 0.97 with the PST obtained from the whole dataset. In 24 patients, the difference was between +/- 10 hr and exceeded 1 day in only 4. CONCLUSION: About 94% of the data may be recovered with only three or four blood samples and the duration may be shortened to 4 days in a significant proportion of patients (48% of ITP patients). This approach offers the advantages of increased patient throughput, compliance and reduced examination costs.

Blood Platelets↗

Quantitative scintigraphic evaluation of total knee arthroplasties: a feasibility study.

For the development and validation of a quantitative approach to the analysis of bone scans after total knee arthroplasty, 39 consecutive patients with 40 prostheses (6 males, 33 females; mean age, 70 years) were scheduled for clinical, radiographic, and scintigraphic examination ranging from 9 to 90 months after surgery. Twenty-seven total knee arthroplasties were considered to be asymptomatic and 13 symptomatic according to the clinical and radiographic findings. Significant differences were found for 99mTc-methylene diphosphonate uptake for femur and tibia and between symptomatic and asymptomatic patients. A reference range was determined for radionuclide uptake in the periprosthetic bone of the 27 asymptomatic total knee arthroplasties; this range was then used to identify loose total knee arthroplasties among the 13 symptomatic knees. With a clinical and radiographic followup performed 1 year after scintigraphy as a standard of comparison, a sensitivity of 88% (7/8) and a specificity of 100% (5/5) was demonstrated. These preliminary results suggest the feasibility of a quantitative approach to the scintigraphic evaluation of total knee arthroplasties after the first postsurgical year.

Aged↗