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Biomedical subjects

A Del Maschio

Publications and source records attributed to A Del Maschio.

At least 19 recordsLinked to original sources

Magnetic resonance imaging of the kidney in type 1 (insulin-dependent) diabetes mellitus.

Reductions in the physiological cortical to medullary signal intensity ratio are found in magnetic resonance scans of the kidney in non-diabetic glomerular disease. Whether this abnormality can also characterise patients with Type 1 (insulin-dependent) diabetes mellitus and nephropathy is not known. We measured the cortical to medullary signal intensity ratio in magnetic resonance images of the kidney in 34 patients with Type 1 diabetes (ten with either clinical proteinuria or raised serum creatinine or both, nine with microalbuminuria, seven with normal urinary albumin excretion and long duration of diabetes and eight with Type 1 diabetes of short duration). The cortical to medullary signal intensity ratio showed a trend to cluster at lower values in the normoalbuminuric patients with normal serum creatinine rather than in the nine healthy individuals, independent of Type 1 diabetes duration (1.47 +/- 0.06 and 1.41 +/- 0.13 vs 1.63 +/- 0.16; five groups Scheffé F-test p = 0.05-0.1). Among the Type 1 diabetic patients, significant reductions in the cortical to medullary signal intensity ratio characterised overt nephropathy (1.19 +/- 0.15, p less than 0.05 vs all groups), but not microalbuminuria (1.47 +/- 0.13, p = NS), concomitantly with low glomerular filtration rate and elevated fractional excretion of uric acid, but independent of glycaemic control. The determinants of the renal cortical to medullary signal intensity ratio in Type 1 diabetes are uncertain. Reductions in the cortical to medullary signal intensity ratio may be a late finding in diabetic nephropathy, and parallel the accompanying impairment in kidney haemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Polymorphonuclear leukocyte adhesion to endothelial cells is inhibited by resting platelets.

The effect of human platelets on the adhesion of polymorphonuclear leukocytes (PMNs) to cultured endothelial cells was investigated. Resting platelets inhibited the adhesion of PMNs stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4), and tumor necrosis factor-alpha (TNF-alpha). Platelets similarly inhibited PMN adhesion induced by endothelial cell activation with TNF-alpha. The inhibitory effect depended on platelet number, was not associated with detectable platelet activation, and was also exerted by paraformaldehyde-fixed platelets. Moreover, supernatants of U46619- or thrombin-stimulated platelets were ineffective, thus excluding a role for constituents released as a result of the platelet-release reaction. Strong inhibition of PMN adhesion was exerted by platelet lysates. The inhibitory activity associated with lysates was sedimentable, heat sensitive, and not dialyzable through a membrane with a molecular-weight cutoff of 8,000; it was directed toward PMNs and was not due to cytotoxic effects or a general inhibition of PMN responsiveness to stimulation, since enzymatic release from activated PMNs was unaffected by platelet lysates. Finally, the activity was not prevented by specific adenosine inhibitors and anti-P-selectin monoclonal antibody. These data suggest that resting platelets can exert an inhibitory effect on PMN adhesion to the vessel wall during inflammatory and thrombotic conditions.

Adenosine

[Accuracy of magnetic resonance (0.5 T) in traumatic lesions of the knee. Controlled 87 cases].

In this study the authors investigated the diagnostic accuracy of Magnetic Resonance (MR) imaging as a method to recognise traumatic disorders of the knee; in particular its capability to identify meniscal and cruciate ligaments tears was examined. The results have been compared with those from arthroscopy and/or surgery, which were considered the gold standard of the study. Eighty-seven consecutive patients with suspected traumatic injury of the knee were prospectively studied. All patients underwent MR examination (0.5 Tesla magnet, gradient echo sequences, slices thickness = 5 mm) and, within 15 days/1 month, arthroscopy or surgery. The high diagnostic accuracy (internal meniscus = 87.5%; external meniscus = 88.5%; anterior cruciate ligament = 93.1%; posterior cruciate ligament = 96.5%) has confirmed the good diagnostic capabilities of MR in assessing traumatic lesions of the knee.

Arthroscopy

Inactivation of endothelin by polymorphonuclear leukocyte-derived lytic enzymes.

Cultured bovine aortic endothelial cells (BAEC) released endothelin-1 (ET-1) in the culture medium in a time-dependent fashion. Coincubation of fMLP-activated human polymorphonuclear leukocytes (PMN) with BAEC caused a fast (maximal activity was reached within 15 minutes) and cell number-dependent disappearance of ET-1 from the medium. This effect was direct to ET-1, because it was also present when PMN were incubated with the synthetic peptide in the absence of BAEC. PMN-dependent disappearance of ET-1 was associated with loss of constrictor activity on isolated rabbit aorta. PMN-released products were responsible for ET-1 degrading activity, because supernatants of activated PMN were equally effective as the intact cells. Resting PMN, in the same time frame, were uneffective. Eglin C, a potent blocker of PMN-derived elastase and cathepsin G, reversed the ET-1 inhibitory activity of fMLP-stimulated PMN and of their supernatant. Direct addition of elastase and cathepsin G to synthetic ET-1 destroyed its immunoreactivity and this effect was blocked by eglin C. High-performance liquid chromatography (HPLC) analysis supported the hypothesis that ET-1 degradation by PMN was due to enzymatic proteolysis. These data provide evidence that activated PMN are able to degrade ET-1 through the release of proteases. Because physiologic concentrations of PMN can destroy high amounts (up to 100 nmol/L) of ET-1 within a few minutes, we propose that this mechanism of ET-1 inactivation has biologic relevance.

Animals

Polymorphonuclear leukocyte-dependent modulation of platelet function: effect of cloricromene.

Cloricromene inhibits the activation of platelets and polymorphonuclear leukocytes (PMN) induced by specific stimuli. We report here that cloricromene caused a concentration-dependent reduction of platelet aggregation, beta-thromboglobulin (beta-TG) release and cytoplasmic Ca2+ movements induced by PMN stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP), and enhanced the inhibitory action of unstimulated PMN on platelet responses to the stable endoperoxide analog U46619. These effects may be of pharmacological interest in view of the multiple interactions between platelets and leukocytes that occur in thrombotic and inflammatory diseases.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

Adrenergic modulation of human polymorphonuclear leukocyte activation. Potentiating effect of adenosine.

The activation of polymorphonuclear leukocytes (PMN) is an important step in the development of tissue damage associated with inflammatory and ischemic conditions. Catecholamines have been reported to inhibit PMN functions, but the high concentrations required cast doubt on their actual relevance as a defense mechanism. We report here that adenosine, which is actively released in ischemic conditions, potentiates the effect of epinephrine and reduces the minimal active concentration required to inhibit PMN activation by at least two orders of magnitude. Epinephrine caused a dose-related reduction of chemiluminescence, superoxide anion generation, enzyme release (lysozyme and beta-glucuronidase), and adhesion to endothelial cell (EC) monolayers in human PMN activated by N-formyl-methionyl-leucyl-phenyl-alanine (fMLP). This effect was only apparent at 10(-7) to 10(-6) mol/L. As expected, adenosine caused dose-dependent reductions of superoxide anion production and PMN adhesion to EC. Adenosine and epinephrine combined had an additive effect on PMN superoxide production and adhesion to EC. The minimal effective concentration of epinephrine in combination with 10(-8) mol/L adenosine was in the range of 10(-10) to 10(-9) mol/L. In contrast, adenosine inhibited only slightly enzyme release and did not significantly enhance the inhibition by epinephrine on this parameter. Studies with adenosine analogs suggested that the potentiating effect of adenosine was mediated by A2 receptors. The mechanism of potentiation was not related to additive effect on intracellular cyclic adenosine monophosphate levels. Epinephrine's ability to modulate PMN activation and the potentiating effect of adenosine may constitute a form of physiologic protection against tissue injury in inflammatory and ischemic processes.

Adenosine

[Invasive carcinoma of the cervix uteri (Stage IB-IIB). Comparison of CT and MR for the assessment of the parametrium].

In the patients with invasive cervical carcinoma, the accurate assessment of parametrial invasion greatly affects the therapeutic choice between surgery and radiation therapy. As a matter of fact, surgery is usually performed only in the patients with carcinoma confined to the cervix, whereas those with parametrial involvement, or more advanced stages, are treated with radiation therapy. This prospective study was aimed at investigating the comparative adequacy of CT and MR imaging in assessing parametrial status in the patients with invasive cervical cancer. Twenty-one consecutive patients, with histologic diagnosis of cervical carcinoma, were investigated. All of them were clinically considered as having invasive cervical cancer (FIGO stages IB-IIB), and subsequently underwent surgery. In all cases, detailed histology of the parametrium was obtained. Pathologic data were compared with CT and MR findings in all cases. As for assessing parametrial involvement by cancer, CT had 62% accuracy, 63% sensitivity, and 60% specificity, versus MR imaging 81% accuracy, 69% sensitivity, and 80% specificity. Therefore, MR imaging appears to be superior to CT in assessing the parametrial status of patients with invasive cervical carcinoma; the method yields valuable information for treatment planning.

Adult

[Treatment of obliterating arteriopathies of the lower limbs using angioplasty. Comparison of 2 techniques of recanalization: Nd-YAG laser and radiofrequency thermal probe].

The Authors report their experience about 20 cases of femoro-popliteal revascularization: in 15 cases a Nd-YAG Laser was used; in 5 cases a unity which employs radiofrequency energy to heat the tip (Thermoprobe) was utilized. We obtained an immediate recanalization in 19 out of 20 superficial femoral arteries with two early thrombosis. In 12 patients of the first group a significant increase of the ankle-brachial index (45%) was seen; it remained unchanged during the follow-up. We had successful revascularization in all the 5 patients of the second group (Thermoplaster). In selected cases, when the lesion is shorter than 10 cm, not completely calcified, and there is a valid run-off, Laser angioplasty could be a valid alternative to surgery or medical therapy.

Aged

Cloricromene inhibits the activation of human platelets by ADP alone or in combination with adrenaline.

Cloricromene may inhibit platelet activation induced by several agonists. In this study we report that ADP and adrenaline synergistically promote platelet aggregation and cytoplasmic Ca2+ movements in aequorin-loaded platelets. Cloricromene caused dose-dependent reduction in platelet aggregation and cytoplasmic Ca2+ movements after exposure of the cells to a low concentration of ADP (2 microM) or to a combination of ADP (2 microM) and adrenaline (10 microM). Cloricromene's inhibitory action may be of considerable pharmacological interest since platelet activation by a combination of agonists may mimic the conditions under which thrombosis occurs in vivo.

Adenosine Diphosphate

Peripheral neuroectodermal tumour (neuroepithelioma) of the thoracopulmonary region: light and electron microscopic cytology.

We describe a case of peripheral neuroectodermal tumour of the thoracopulmonary region diagnosed by fine needle aspiration cytology. Light microscope examination revealed numerous small tumour cells arranged in large irregular aggregates occasionally delimiting empty vascular-type spaces or forming rosette-like structures. Cytologically the tumour cells showed a marked degree of nuclear anaplasia, scanty cytoplasm and long thin cytoplasmic processes. Electron microscopy revealed cells with characteristics of neuroectodermal differentiation.

Humans

Platelet activation by polymorphonuclear leukocytes exposed to chemotactic agents.

Human platelets were loaded with aequorin, a Ca2(+)-sensitive photoprotein, and tested in the platelet-ionized calcium aggregometer for simultaneous recording of platelet aggregation and intraplatelet Ca2+ levels both in the presence and in the absence of autologous polymorphonuclear leukocytes. Cells were exposed to one of three chemotactic stimuli: platelet-activating factor (PAF), N-formyl-methionyl-leucyl-phenylalanine (FMLP), or leukotriene B4 (LTB4). Platelets alone aggregated and showed intracellular Ca2+ movement only when exposed to PAF. Amplification of both platelet aggregation and intraplatelet Ca2+ movement was induced by PAF in the presence of leukocytes. Aggregation and intraplatelet Ca2+ mobilization were also observed in the presence of leukocytes activated by either FMLP or LTB4. Both parameters increased with the concentration of the stimuli and/or the number of leukocytes. Platelet thromboxane B2 production was also significantly increased in the presence of leukocytes. Addition of platelets at different times after leukocyte activation resulted in progressively reduced cytoplasmic Ca2+ increase. Cell-free supernatants prepared from FMLP-stimulated leukocytes were able to induce platelet aggregation, thromboxane B2 generation, and Ca2+ mobilization, although at a reduced degree as compared with intact leukocyte addition. The activity of leukocyte supernatants was stable at 37 degrees C for up to 30 min and was suppressed by trypsin inhibitor. Our study indicates that stimulated leukocytes release a soluble enzymatic activity able to activate platelets; cell-to-cell interaction may also play a role in this phenomenon. Platelet-leukocyte interaction could have physiopathological relevance and constitutes a new model for studying old and new platelet inhibitory drugs.

Blood Platelets

Inhibition of platelet function by polymorphonuclear leukocytes.

Human polymorphonuclear leukocytes (PMNs) were evaluated for their ability to modulate platelet response induced by collagen, thrombin, platelet-activating factor and the stable analog of cyclic endoperoxides U46619. Platelet aggregation was first evaluated in whole blood and in leukocyte-depleted whole blood by the impedance method. This novel approach highlighted the inhibitory role of leukocytes on platelet aggregation in whole blood. The inhibitory role of PMNs on platelet function was subsequently evaluated on washed cells. PMN inhibition of platelet aggregation and beta-thromboglobulin release was more evident with threshold concentrations of stimuli. The inhibition also depended on the number of PMNs incubated in mixed cellular suspensions. Higher concentrations of stimuli may overcome the PMN-dependent inhibition. Under this condition, preincubation of cells with N-formyl-methionyl-leucyl-phenylalanine (a specific PMN agonist) restored the inhibitory effect of PMNs on platelet aggregation in whole blood and in mixed cellular suspensions. Not only PMNs, but also PMN-derived supernatants, dose-dependently inhibited U46619-induced platelet aggregation, suggesting that the inhibition observed may be exerted by chemically stable compound(s). Cytoplasmic Ca2+ movement was measured in aequorin-loaded platelets exposed to thrombin or U46619 to see whether cytoplasmic Ca2+ levels were affected by PMN. Ca2+ levels were similar in the presence or absence of PMNs, suggesting that inhibition may be related to a subsequent platelet response step. A series of bioassay experiments showed that PMNs were able to remove and/or convert adenosine diphosphate available for platelet aggregation but not to reduce U46619 availability. Our findings suggest that (1) unstimulated PMNs may release factor(s) that inhibit platelet aggregation and beta-thromboglobulin release; (2) this in itself is sufficient to block the platelet response to a threshold concentration of stimuli; (3) release of the same or other inhibitory mediators from stimulated PMNs may have to be greater to inhibit platelet response to higher concentrations of stimuli. Data presented here suggest that adenosine diphosphatase activity and chemically stable, as yet unidentified, compounds besides previously well-characterized labile compounds such as nitric oxide and arachidonic acid metabolites are responsible for the PMN-dependent mechanism of inhibition of platelet response that could be relevant in physiopathologic conditions.

Adenosine Diphosphate

[Invasive carcinoma of the cervix uteri (stage IB-IIB): evaluation using magnetic resonance].

In patients with cervical carcinoma the selection of the optimal therapy depends on the precise preoperative assessment of the extent of disease. Currently, decisions regarding the management of these patients are made on the basis of clinical (FIGO) staging that has 50% mean error rate. To investigate the value of MR imaging in staging patients with invasive cervical cancer, we performed 25 MR examinations on 23 patients with histologic diagnosis of cervical cancer. All patients were clinically considered as having stage IB or IIB disease and underwent radical hysterectomy, providing specimens for pathologic correlation. The overall accuracy of MR imaging in staging cervical carcinoma (stage IB-IIB) was 78.1%. MR imaging seems to be the most reliable preoperative modality for staging invasive cervical cancer.

Adult