Previously irradiated areas spared from skin toxicity induced by cetuximab in six patients: implications for the administration of EGFR inhibitors in previously irradiated patients.
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Publications and source records attributed to C Bergamini.
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New flat-panel direct digital radiography equipment has recently been installed in our Accident and Emergency Department; its characteristics and versatility are well suited to the work undertaken in this environment. The aim of this study was to compare radiation doses to patients undergoing standard radiographic examinations using conventional screen-film radiography, computed radiography and direct digital radiography; entrance surface dose and effective dose were calculated for six standard examinations (a total of 10 projections) using standard patient exposure parameters for the three imaging modalities. It was found that doses for computed radiography (all examinations) were higher than the doses for the other two modalities; effective doses for direct digital radiography were approximately 29% and approximately 43% lower than those for screen-film radiography and computed radiography, respectively. The image quality met the criteria in the European guidelines for all modalities.
BACKGROUND & AIMS: How hepatocellular carcinoma (HCC) cells acquire the ability to invade surrounding tissue is unknown, but epithelial mesenchymal transition (EMT) likely plays a role. We investigate how transforming growth factor (TGF)-beta1 and extracellular matrix protein Laminin-5 (Ln-5) induce EMT and cancer invasion. METHODS: Snail, Slug, E-cadherin, beta-catenin and Ln-5 were investigated on HCC tissues and on HCC cell lines. RESULTS: We show that in HCC but not in peritumoral tissue of the same HCC patients, Ln-5, Snail, and Slug are up-regulated, E-cadherin is down-regulated and beta-catenin is translocated into the nuclei. In vitro, HCC "invasive" cells, partially EMT-transformed, show low levels of E-cadherin. In presence of Ln-5, Snail, and Slug are up-regulated, E-cadherin is down-regulated, beta-catenin is translocated into the nuclei, and cells undergo a dramatic morphological change, becoming scattered and undergoing a complete EMT. This effect is reversed by anti-alpha3 but not by anti-alpha6 integrin blocking antibody. HCC "noninvasive" cells are not EMT-transformed, and have constitutively high levels of E-cadherin. In presence of Ln-5, cells undergo partial EMT, Snail, and Slug are up-regulated, E-cadherin is down-regulated but cells do not scatter. However, the presence of both Ln-5 and TGF-beta1 completes the EMT process, beta-catenin is translocated into the nuclei, cells scatter and become invasive, recalling the "invasive" cells. In this case, too, the effect is reversed by anti-alpha3 integrin blocking antibody. CONCLUSIONS: Our study shows that Ln-5 and TGF-beta1 cooperatively induce EMT in HCC, suggesting the microenvironment as a potential target for new biological therapies.
A transglutaminase (TGase; EC 2.3.2.13) activity, which shared many properties with the TGase activity of the Helianthus tuberosus chloroplast, was observed in the Zea mays L. chloroplast and in its fractions. This activity was found to be prevalent in thylakoids; bis-(glutamyl) spermidine and bis-(glutamyl) putrescine were the main polyamine conjugates formed. Light stimulated the endogenous thylakoid activity. Putrescine, spermidine and spermine were conjugated to the isolated light-harvesting complex of photosystem II (LHCII) with different degrees of efficiency, spermine being the polyamine most efficiently conjugated. A TGase with a light-sensitive activity was identified in the photosystem II-enriched fraction. Its partial purification on a sucrose gradient allowed the separation of a 39-kDa band, which was immunorecognised by two anti-TGase antibodies (Ab-3 and rat prostatic gland-TGase). Both a colorimetric and a radiometric assay for TGase activity, the former carried out in the presence of biotinylated cadaverine and the latter in the presence of polyamines labelled with radioactive isotopes and resulting in the isolation of glutamyl-polyamines, further confirmed that the thylakoid enzyme is indeed a calcium-dependent transglutaminase (Thyl-TGase). At variance with guinea pig liver and erythrocyte TGases, which are insensitive to light, the activity of the thylakoid transglutaminase is affected by light. Moreover, this enzyme, when tested with purified LHCII as substrate, catalysed the production of mono- and bis-glutamyl-polyamines in equal amounts, whereas the 'animal' enzymes produced mainly mono-derivatives. Herein, it is discussed whether this light sensitivity is due to the enzyme or the substrate.
INTRODUCTION: Total thyroidectomy (TT) is considered to be more efficient and more widely used than conservative thyroidectomy (CT) in patients with differenziated thyroid cancer (DTC). Anyway recently CT has been reevaluated in the treatment of DTC sharing favorable prognostic factors, due to the introduction of mini-invasive neck surgery. Such technique are indeed more feasibly applicable to CT than to TT. In this retrospective study we report the results of these surgical approaches in a series of patients with DTC. PATIENTS AND METHODS: Since 1985 up to 2002, 329 patients with thyroid neoplasm (134 female, aged between 13 and 88) underwent to surgery in our Department. Sixty-three were diagnosed as non-DTC and therefore excluded from this study. The remaining 266 were divided into two groups according with the surgical treatment: the I group (82 patients) underwent to CT, the II group (184 patients) had TT. Several clinical/pathological parameters were analyzed in comparison in the two groups. RESULTS: 60.3% of TT and 80.4% of CT had a single node presentation (p < 0.001 chi-square), whereas multinodular presentation was found in 28.4% of TT and in only case of CT. The mean size of the node was 2.9 +/- 0.8 cm in TT and 1.3 +/- 0.5 in CT (p = < 0.001 t-test). The follicular hystotype was more frequent in TT (37%) than in CT (13%) (p = 0.006 chi-square), whereas papillary form and capsule invading tumors were equally distributed. There was a lymphatic involvement in 20% of TT. Peri-operative mortality is absent; transitory and definitive recurrent nerve lesions were more frequent in TT then n CT (2.1% vs 1.2%); 2.2% of TT and no case in CT had hypoparatiroidism. Ten TT patients (5.5%) and 3 CT cancer (3.6%) died for thyroid cancer. Out of the latter 2 had a capsule-infiltrating form. Finally 4 CT patients had controlateral recurrence (4.8%): two of them had a follicular form and two a papillar one, with mean size of 2.5 cm. CONCLUSIONS: Although TT is currently considered as the approach of choice for the oncologic accuracy and the correct follow-up, CT is having increasing application for low-risk patients in open and video-assisted surgery especially in the case of an incidental post-operative diagnosis of malignancy. The increasing use of modern technology such as high resolution ultrasounds and nuclear imaging (PET) will allow a more accurate follow-up of CT patients, with an early recognition of either lymphatic or local recurrences.
Asbestos fibers, such as chrysotile and crocidolite, are known to have cytotoxic effects on different cell types. in vivo exposure to asbestos fibers can induce both fibrotic and malignant lung diseases , however, the mechanisms linking exposure to the subsequent development of the diseases are unknown. Numerous investigations suggest the involvement of reactive oxygen species (ROS). ROS are known to damage biological macromolecules including proteins, cell membrane lipids and nucleic acids; alterations of these essential cellular components can alter cell function and can drive the cell to neoplastic transformation or to cell death. Because the mitochondrial respiratory chain is an important source of ROS and RNS (reactive nitogen species) in the cells, we have investigated the effects of aqueous extracts of asbestos (natural and synthetic) fibers on some mitochondrial activities. Our data show that crocidolite fibers release substances in solution that may interfere directly with the mitochondrial cytochrome oxidase complex. Moreover, the calcium ions released from these fibers induce opening of the permeability transition pore of the inner membrane leading to a possible cytotoxic effect due to the release of apoptotic factors normally localized in the mitochondrial intermembrane space. In addition, crocidolite extracts enhance the mitochondrial production of ROS. No significant biochemical effects are exerted by chrysotile, either natural or synthetic, on isolated mitochondria. Nevertheless, all asbestos fibers tested induce morphological alterations visualized by transmission electron microscopy and morphometric analysis.
BACKGROUND: Laparoscopic adrenalectomy has proved to be the technique of choice for managing benign pathologies of the adrenals and isolated adrenal metastases, especially those arising from lung tumor, but the procedure should not be performed for primitive adrenal carcinoma. The Authors wanted to test the advantages of the Harmonic Scalpel in laparoscopic adrenalectomy. METHODS: From April 1995 to April 2001, the authors investigated their series of laparoscopic adrenalectomies performed at the Careggi General Hospital, Division of General and Vascular Surgery, Florence, Italy. This study enrolled 91 patients with various adrenal pathologies. The transperitoneal approach was used, with the patient in a lateral position, as suggested by Gagner. Special care was taken to improve the surgical approach to the adrenals by the use of new technological devices such as the Harmonic Scalpel. The operative time required by the surgical procedure was computed by dividing the study into three periods: 1995-1997, 1998-1999, 2000-2001. The first period was necessary to complete the learning curve. In the second period, a steady state in surgical time was reached. During the third period, the Harmonic Scalpel was introduced. The differences between the three periods were tested using a nonparametric analysis (Mann-Whitney U test or Kruskal-Wallis test) as appropriate. A two-tailed p value of 0.05 or less was considered statistically significant. The authors investigated the cost of the operation performed in each of the two groups using, respectively, the conventional laparoscopic device (1998-1999) and the Harmonic Scalpel (2000-2001). The following expenses were considered: Harmonic Scalpel impulse generator and disposable shears, operating room cost per hour, and endoclip applier. RESULTS: The 91 laparoscopic adrenalectomies were performed with these indications: 31 incidentalomas (26 adenomas and 5 cysts), 25 cases of Conn's disease, 18 cases of Cushing's disease, 9 pheochromocytomas, 2 myelolipomas, 5 metastases (from lung, kidney, and breast) and 1 primitive carcinoma diagnosed preoperatively. Considering the whole series (1995-2001), there was a significant trend of reduction in operative time (p = 0.0001). Moreover looking at the first period (1995-1997), in which the learning curve was completed, the mean surgical time was 148 min, as compared with 125 mm. For the second period (1998-1999) (p = 0.0002). This represents a significant reduction in operative time. The authors noted a further reduction in the operative time when surgery was performed with the Harmonic Scalpel (2000-2001) (92 min; p = 0.001). The reduction in operative time attributable to the Harmonic Scalpel was confirmed also by a multivariate analysis of covariance general linear models procedure (GLM), which accounts for several confounders: age, gender, site and size of tumors, and histology (p = 0.0001). The rate was 3.3% for morbidity, 1.1% for mortality, and 2.2% for conversion. There was no difference in complications between patients treated with conventional devices and those treated with the Harmonic Scalpel. CONCLUSIONS: The laparoscopic approach has proved to be an extremely reliable procedure for benign pathologies and isolated metastases. There may yet be doubts about its use for the treatment of adrenal carcinomas preoperatively diagnosed. When surgery is performed using Harmonic Scalpel, operative time is significantly reduced and surgery is easier and less expensive. Infact use of the Harmonic Scalpel allowed the cost per operation to be reduced $70. Moreover, if surgery is performed using the nondisposable clip applier, the expenses are reduced $105.
Hepatocellular carcinoma (HCC) is the most frequent malignant tumor of the liver; prognosis depends on the tendency to metastasize. Cancer cell invasion is regulated by proteolytic remodeling of extracellular matrix components and by integrin expression. We have shown that matrix metalloproteinase-2 (MMP-2) and membrane-type-1 matrix metalloproteinase (MT1-MMP) cleave Laminin-5 (Ln-5), stimulating cell migration. Here we report that all HCC cells express MT1-MMP, migrate on Ln-1 and Collagen IV, whereas only HCC cells that express alpha3beta1 integrin secrete detectable levels of gelatinases, migrate on Ln-5, and invade through a reconstituted basement membrane (BM). Migration on Ln-5 is blocked by BB-94, an MMP inhibitor, and by MIG1, a monoclonal antibody that hinders migration on MMP-2-cleaved Ln-5. Invasion through a reconstituted BM is also inhibited by BB-94. HCC alpha3beta1-negative cells migrate on Ln-1 and Collagen IV, but not on Ln-5, and do not invade through a reconstituted BM, although they express MT1-MMP. Anti-alpha3beta1 blocking antibodies inhibit gelatinase activation, cell motility, and cell invasion through MATRIGEL: In vivo, alpha3beta1 integrin and Ln-5 are expressed in HCC tissue but not in normal liver. In conclusion, our data suggest that both alpha3beta1 integrin and gelatinase activity are required for HCC migration and invasion.
The broad resistance to antibody-mediated neutralization of lentiviruses recently isolated from infected hosts is a poorly understood feature which might contribute to the ability of these viruses to persist and to the failure of experimental vaccines to protect against virulent viruses. We studied the underlying molecular mechanisms by examining the evolution of a neutralization-sensitive, tissue culture-adapted strain of feline immunodeficiency virus upon reinoculation into specific-pathogen-free cats. Reversion to broad neutralization resistance was observed in seven of seven inoculated animals and, in individual hosts, started to develop between less than 4 and more than 15 months from infection. After comparison of the envelope sequences of the inoculum virus, of an additional 4 neutralization-sensitive in vitro variants, and of 14 ex vivo-derived variants (6 neutralization sensitive, 5 resistant, and 3 with intermediate phenotype), a Lys-->Asn or -->Glu change at position 481 in the V4 region of the surface glycoprotein appeared as a key player in the reversion. This conclusion was confirmed by mutagenesis of molecularly cloned virus. Analysis of viral quasispecies and biological clones showed that the intermediate phenotype was due to transient coexistence of neutralization-sensitive and -resistant variants. Since the amino acid position involved was the same in four of four recent revertants, it is suggested that the number of residues that control reversion to broad neutralization resistance in FIV might be very limited. Amino acid 481 was found to be changed only in one of three putative long-term revertants. These variants shared a Ser-->Asn change at position 557 in region V5, which probably collaborated with other mutations in long-term maintenance of neutralization resistance, as suggested by the study of mutagenized virus.
Laparoscopic adrenalectomy has proved to be the technique of choice for the treatment of benign pathologies of the adrenals and also for the treatment of isolated adrenal metastases, especially arising from lung tumor, but it shouldn't be performed for primitive adrenal carcinoma. The harmonic scalpel is very useful for laparoscopic adrenalectomy showing a significant reduction in operative time. The Authors retrospectively investigated 78 laparoscopic adrenalectomies performed from April 1995 to April 2000 using a transperitoneal approach with the patient on a lateral position as suggested by Gagner. Special care was taken to improve the surgical approach to the adrenals also by means of new technological devices as the Harmonic scalpel. The 78 laparoscopic adrenalectomies were performed in 70 cases for benign neoplasms: incidentalomas 24, Cushing's disease 16, Conn's disease 20, pheochromocytomas 9, myelolipoma 1. In the remaining 8 patients laparoscopic adrenalectomy was performed in 7 cases for isolated adrenal masses (5 metastases, 2 adenomas) in neoplastic patients, and in 1 patient for a preoperatively diagnosed adrenal carcinoma. Patients operated for functioning neoplasms had all remission or improvement of symptoms and humoral parameters; patients operated for isolated adrenal metastases showed this survival: 3 patients 3 years asymptomatic and disease free, 1 patient 18 months, and 3 patients are still alive and healthy after 6-12-15 months. A fast onset of local recurrence was seen in a patient operated for a preoperatively diagnosed adrenal carcinoma. We analyzed the operating time dividing the patients in three groups: a) 14 patients operated in the first semester of 1998 when we completed the training curve (average operative time 120.7 minutes); b) 14 patients operated from 1998-1999 (average operative time 118 minutes); c) the last 14 patients (operated from December 1999 to April 2000) where surgery was performed using the Harmonic scalpel (HS) (average operative time 94 minutes). The analysis of the average operative time comparing groups B and C using T-Student Test showed a significant reduction (p = 0.004). The morbility rate was 2.6%, mortality 1.3%, and a conversion rate of 2.6%. Laparoscopic approach results to be an extremely reliable procedure also for the treatment of incidentalomas up to 4-5 cm in which the incidence of adrenal carcinoma is about 13%. Doubts may yet result for the treatment of adrenal carcinomas preoperatively diagnosed. When laparoscopic adrenalectomy in performed using HS the operative time is significantly reduced and surgery is easier.
In this study, the binding of naturally occurring antibodies as well as of induced anti-spectrin antibodies to red blood cells (RBC), in relation with different ageing conditions, was investigated in the rat. RBC from aged animals, or from rats whose RBC were age-induced either by means of hypertransfusion (which blocks erythropoiesis) or by treatment with clodronate-containing liposomes (which reduces RBC removal from circulation), were used. Attainment of RBC ageing was demonstrated by MCV reduction and by an increase of both RBC density and 4.1a/4.1b RBC membrane protein ratio. The results demonstrate an augmented anti-spectrin antibody binding to RBC in relation with their ageing condition, especially when induced by hypertransfusion. The vesiculation process was also investigated and correlated with antibody binding: vesicles were found only in the plasma of clodronate-treated rats, whose RBC showed the lowest level of anti-spectrin antibody binding with respect to the other groups. In addition, RBC preserved in vitro in different media showed a binding of anti-spectrin antibody, which inversely correlated with the vesiculation process. On the whole, the latter results suggest a protective effect of vesicles towards IgG opsonization of aged RBC.
The therapeutic guidelines of Basedow (Graves') disease are based on three different approaches: medical treatment with anti-thyroid drugs, radio-iodine therapy and surgery. This choice has increasing consensus for the great improvement of the techniques, which at the moment are practically free of mortality risks, and have very low morbidity incidence, as well as for its positive influence on the course of the Graves' ophthalmopathy. For authors' study 180 patients affected with Graves disease, who have undergone total thyroidectomy, were retrospectively enrolled. The results show that hyperthyroidism symptoms are almost completely cured in most of the subjects, with a very low rate of complications as related to nervous (ricorrential) and parathyroid gland function. Furthermore, total thyroidectomy has resulted to have a positive impact in the clinical course of Graves' ophthalmopathy, particularly regarding some aspects of the eyes involvement, which have a dramatic effect in the "quo ad valitudinem" prognosis of these patients.
In order to analyse a possible role of anti-spectrin antibodies in the clearance of aged red blood cells (RBC), a homologous system was employed, whereby a population of aged RBC, obtained by hypertransfusion, was injected into rats bearing a high level of anti-spectrin antibodies, following immunization with spectrin. The aged RBC bound the anti-spectrin antibodies 'in vitro' and were eliminated from circulation in spectrin-treated rats at a faster rate than in control rats with naturally occurring antibodies. The analysis of the clearance curves revealed aged RBC of heterogeneous lifespans: two principal populations of short- and longer-living could be identified. In rats with anti-spectrin antibodies, the survival of the short-living population was further reduced. However, the similar kinetics of elimination of aged RBC in the two groups (with naturally-occurring and induced antibodies, respectively) suggest that anti-spectrin antibodies strengthened the intervention of the naturally-occurring ones. On the basis of these results, we assume that during their aging in circulation, RBC can accumulate surface alterations to make spectrin accessible to antibodies so that, in addition to anti-band 3 antibodies, anti-spectrin antibodies may contribute to their elimination.
INTRODUCTION: "Receiver Operating Characteristic" (ROC) curves are one of the most efficient analysis tools for the complete evaluation of a diagnostic system performance. However this method is limited in visualizing and locating abnormal structures, such as clusters of microcalcifications on mammographic images. Other more refined and complex techniques have also been suggested, where particular statistical hypotheses are assumed, namely the "Free-response ROC" (FROC), the "Alternative FROC" (AFROC) and the "Free-response Forced Error" (FFE) analyses. We studied the theoretical bases of these different methods and their experimental applications to assess the correctness of the hypothetical statistical distributions. MATERIAL AND METHODS: We considered two statistical hypotheses: first, that the false-positive response distribution follows the Poissonian statistics; second, that "signal" and "noise" distributions have a Gaussian trend with different means and variances. Thus, we applied the different methods to the responses given by 8 observers (5 radiologists and 3 medical physicists) who independently evaluated 3 digital mammographic samples. Every sample consisted of 39 images, with 1-15 clusters each (total: 100 clusters). The samples were obtained from 39 images available in an Internet database (sample 1); 2 different digital filters were applied to each image (samples 2 and 3). To collects responses, we provided for two phases: first, every observer visualized and located the clusters at a given confidence level; second, when a false-positive response was given, spontaneously or after forcing, the responses were ordered by decreasing conspicuity. Finally, data were analyzed with a "home-made" software by applying the FROC and AFROC analyses to the data collected in phase 1 and the FFE analysis to those collected in phase 2. RESULTS: We considered the area under the AFROC curve as the most important parameter: the values obtained with the 3 types of analysis are well in agreement within their uncertainties. In particular, the FROC-AFROC agreement did not exceed 5.9% (10 of 14 cases within 2.5%), while the FFE analysis had higher standard deviations associated with the area value (about 10%). The interpolated curves from both FROC and AFROC data were very similar. The three methods had various advantages: the FFE is very simple to calculate and makes the most of the information given by the observer; FROC and AFROC can provide true-positive and false-positive responses on the same image, which permits to optimize the evaluation of a diagnostic system performance. The statistical tools used in the simplest methods are usually integrated with the completeness characteristics of the location of multiple signals on mammograms. CONCLUSIONS: In theory, every method is necessary because it provides additional information to validate the statistical hypotheses under investigation. In fact, when the methods are used to evaluate and compare several diagnostic systems, the results of the three techniques are equivalent. Therefore, choosing a specific technique depends on both available resources and response type all the hypothetical statistical distributions in our study proved correct.
PURPOSE: The aim of this project was to analyze and validate the diagnostic applications of Volumetric High Resolution CT in the study of focal or diffuse infiltrative lung disease compared with High Resolution CT. To date HRCT is the gold standard in the assessment of infiltrative lung diseases, but it shows some limitations such as artifacts due to both respiratory and cardiac motions, as well as the need for multiple breath-holds. MATERIAL AND METHODS: September, 1996, to September, 1997, anthropomorphic test phantoms and a group of 34 subjects (8 without lung disease and 26 with aspecific lung disease: TBC, BPCO, micronodular conditions, cardiogenic interstitial pulmonary edema) were submitted to both HRCT and VHRCT. VHRCT was carried out with a 3-mm slab thickness and the images were reconstructed with a 1-mm interval and processed with MIP and MinIP reconstructions. With both techniques we compared some physical parameters (slice sensitivity profile, noise, longitudinal resolution) and some radiographic findings (central and peripheral airways lumen, peripheral vessels, nodular and interstitial abnormalities, emphysema foci, focal areas of ground glass pattern and bronchiectasis). We calculated the radiation exposure dose of both HRCT and VHRCT, also testing a low-dose protocol. RESULTS: The analysis of physical parameters showed no major differences between HRCT and VHRCT regarding longitudinal resolution, while minimal advantages were found with HRCT for slice sensitivity profile and image noise. Radiographic analysis showed additional findings in 27% of patients with nodular disease using VHRCT-MIP in 8% of patients with emphysema and 25% of cases with focal areas of ground glass opacities, using VHRCT-MinIP. Relative to HRCT findings, VHRCT better depicted all patterns but subpleural nodules. The surface radiation dose was 2.8 times higher with VHRCT than HRCT. It is possible to halve radiation exposure using a low dose protocol (120 kV, 110-150 mA). CONCLUSIONS: Our study provides conclusive results concerning the use of VHRCT with standard technical parameters because this technique showed some advantages in the study of a wide range of diffuse or focal lung diseases. We suggest that this protocol be applied only in patients with mild forms of lung disease or in the cases of difficult interpretation, such as suspicious abnormal areas at HRCT, because its doses are higher. Out low-dose protocol is currently on trial but we expect promising results.
Neurological disorders occurring in the primary antiphospholipid syndrome (neuro-PAPS) have not yet been completely understood. Platelet activation has been suggested to play a crucial role in the pathogenesis of hemostatic disorders in the antiphospholipid syndrome, but no association with neuro-PAPS has been investigated so far. Therefore, we investigated 16 patients with PAPS by flow cytometry in the presence of circulating activated platelets as defined by the surface expression of activation-dependent glycoprotein CD62. In addition, the relationship among activated platelets and anticardiolipin antibodies (aCL) was evaluated. Compared to normal subjects CD62 was found significantly increased in these patients. Furthermore, a significantly increased percentage of CD62-positive platelets was found in the neuro-PAPS group (nine patients) compared to the non-neuro-PAPS patients (seven subjects). On the contrary, no significant difference was found between the two groups with regard to aCL IgG and platelet number. Furthermore, within the neuro-PAPS group, no difference was evidenced, in the CD62-positive platelet percentage, between the four subjects with thrombocytopenia and the five with the normal blood platelet count. Similarly, neuro-PAPS subjects with previous peripheral arterial and/or venous thrombosis did not show a significantly more elevated level of CD62-positive platelets. Finally, a linear correlation was found between the aCL IgG level and the CD62-positive platelet percentage in all the patients and, more significantly, in the neuro-PAPS group, but not within the non-neuro-PAPS patients. Our data demonstrate that circulating activated platelets are detectable by flow cytometry in the majority of PAPS patients and suggest the existence of a relationship among activated platelets, aCL, and neurological disease that patients affected by PAPS might undergo.
Platelet activation has been suggested to play a crucial role in the pathogenesis of haemostatic disorders in antiphospholipid syndrome (APS). In 16 patients with primary APS (PAPS) we investigated by flow cytometry the presence of circulating activated platelets as defined by the surface expression of activation-dependent glycoproteins CD62 and CD63. In addition, the relationships among activated platelets, thrombocytopenia, antiphospholipid antibodies (aPL) and platelet associated IgG (PalgG) were evaluated. Compared to normal subjects CD62, but not CD63 expression, was found significantly increased in patients. All thrombocytopenic subjects showed a percentage of CD62 expressing platelets above the cut off. In thrombocytopenics a significantly increased percentage of CD62 and higher levels of aCL IgG were found compared to PAPS patients with normal platelet count. No correlation was found between activated platelets and both lupus anticoagulant antibodies and PalgG. Our data demonstrate that circulating activated platelets are detectable by flow cytometry in the majority of PAPS patients and suggest the existence of a relationship among activated platelets, thrombocytopenia and aPL levels.
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