An uncommon heart tumor: the fibrosarcoma.
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Biomedical subjects
Publications and source records attributed to V Coppola.
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The haemodynamic and electrophysiological benefits of dual chamber pacing are well recognized at the cost of a more complex and expensive implant. In selected groups of patients VDD-mode dual chamber pacing offers the advantages of dual chamber pacing with the use of a single catheter and is nowadays gaining increasing popularity. The following report describes an uncommon and potentially harmful pacemaker malfunction secondary to the dislodgement of the catheter.
INTRODUCTION: Diagnostic imaging in emergency rooms may be inadequate and delayed, which makes chest traumas in children more severe and difficult to treat. We carried out a retrospective study on adults and children who had survived major chest traumas involving the respiratory tract to assess the differences between the two age groups and the role of emergency CT. MATERIAL AND METHODS: Our series consisted of fourteen children admitted to the emergency department for various accidents. Home accidents prevailed (9/14 = 64.3%). On admission, chest radiography was performed in most cases (11/14 = 78.6%); CT was carried out in 21.4% (3/14 patients). RESULTS: Trauma involved more organs in pediatric patients (11/14 = 78.6%) and lung involvement was always associated with other types of injury, namely contusion (14/14 = 100%), pneumothorax (11/14 = 78.6%), hemothorax (10/14 = 71.4%), tear (4/14 = 28.6%). CT corrected or integrated the radiographic findings of contusion focus in 67% (8/14) and that of pneumothorax in 63.6%; both patterns cannot be demonstrated otherwise. DISCUSSION: Mixed and multiple posterior parenchymal injuries with no rib fractures prevail in young subjects because their bones and ligaments are more elastic, which may lead to trauma underestimation. Tracheobronchial ruptures and pneumomediastinum are much more severe in children than in adults. Chest plain film is often the only diagnostic tool used, despite its major technical and interpretative limitations, also because skull and abdomen are the most investigated regions. Executive limitations are stronger in childhood, increasing the margin of error and the risk of delayed treatment. CT is as cost-effective as radiography and shows even the injuries missed or poorly depicted on conventional images; CT also gives accurate information on damage severity and nature. CONCLUSIONS: Traumatic injuries are more severe in pediatric patients due to their build and to biomechanical, clinical and management factors. Spiral CT should be considered the examination of choice to be performed in the emergency department equipped also for pediatric re-animation.
PURPOSE: To assess the role and the diagnostic yield of CT and of endoscopic retrograde cholangiopancreatography (ERCP) in the study of emergency pancreatic injuries from blunt abdominal trauma. MATERIAL AND METHODS: January, 1992, to December, 1996, eleven subjects with pancreatic trauma were operated on. The patients were 8 men and 3 women (mean age: 28.4 years, range: 15-47 years) with pancreatic traumas of different severity but all with gland fracture and severe ductal injuries. Direct radiography was performed in all cases in different projections: CT with 1 cm slice thickness and feed was also performed. A contrast agent was administered orally in 8/11 patients and i.v. in 11/11. ERCP was performed in supine recumbency within 12 hours of trauma; a hypotonic agent was administered i.v. in 5 cases. The examination was successful in 10 patients. Wirsung duct studies were extended to the biliary tract in 6 cases. RESULTS: Pancreatic traumas were never isolated and usually associated with other abdominal injuries in the liver, spleen, small intestine, kidneys (by frequency) and with injuries in other body regions--the chest in 8/9 cases, limbs in 7/9, the spine in 4/9 and the skull-brain in 3/9 cases. Pancreatic fractures were mostly cervical and 3 of them were bifocal. The radiologic findings of pneumoperitoneum (4 cases), sentinel loop (3), paralytic ileum (11), air-fluid levels (9) were always aspecific. CT had 66.7% sensitivity, with over-all accuracy of pancreatic involvement by trauma in 5/11 cases and specific findings of fracture in 1/11 cases. CT showed associated parenchymal injuries in both the abdomen and other sites. ERCP diagnostic accuracy and sensitivity topped 100% in the demonstration of ductal injuries. DISCUSSION: Pancreatic traumas are usually a rather uncommon event. They are classified as major and minor according to the extent and severity of ductal involvement. Injury site corresponds to the direction of impact force, but the neck is the preferential site for fractures because it is compressed within the spine and extended. Clinical findings are usually aspecific and questionable and diagnostic imaging, especially CT, plays therefore a major role in treatment planning. However, CT provides mainly indirect signs and fails to depict ductal rupture. Despite its difficult technical execution in emergency, ERCP shows ductal injuries with extreme accuracy and specificity, which finding is indispensable for treatment planning. CONCLUSIONS: Both CT and ERCP are necessary tools to diagnose pancreatic fractures: the former because it provides indispensable panoramic findings and the latter because it is the only method showing ductal involvement. Therefore, both techniques should be used for accurate surgical planning, which is a crucial step for the prognosis of these injuries. Cost-effectiveness and safe execution are well balanced.
Epstein-Barr virus (EBV) type and strain variations were examined using both lymphoblastoid cell lines (LCLs), spontaneously derived in vitro from peripheral blood mononuclear cells (PBMC) of 15 HIV-1-seropositive individuals; and SCID mouse tumours induced by inoculation of PBMC from 11 healthy human donors (Hu-SCID tumours). Polymerase chain reaction (PCR) analysis disclosed that all but one of the 26 EBV + samples harboured EBV nuclear antigen (EBNA) 2 and 3C type A virus. On the other hand, single strand conformation polymorphism (SSCP) analysis using Epstein-Barr encoded RNA (EBER) specific primers detected an AG876-like (type B) band pattern in 21 of the 26 EBV + samples. Three Hu-SCID tumours scored as B95.8-like (type A), and two showed neither a type A nor a type B SSCP migration pattern. Sequence analysis of the amplified EBER fragments confirmed the PCR-SSCP findings; moreover, additional mutations were present not only in the two EBV + samples with anomalous SSCP pattern, but also in two other samples with a standard SSCP profile. Thus, EBER analysis did not correlate with EBNA typing, and appeared to be unsuitable for EBV type assessment. Latent membrane protein (LMP) analysis disclosed, on the whole, sever size variants: as expected, the differences were due to the variable numbers of a 33-bp repeat in the amplified fragment, as assessed by direct sequencing. The broader variability detected by LMP analysis should prove more useful than typing for assessing the presence of single and/or mixed variants resulting from EBV reactivation and/or reinfection.
The chance isolation of a mouse strain mutant that shows a complete deficiency in both the humoral and cellular immunity compartments has opened new perspectives in numerous fields of medicine and biology, including oncology, hematology and immunology. However, the original concept that the severe combined immunodeficiency mouse might behave as a 'living vessel', and allow experimental approaches that are precluded in man by technical and ethical constraints, has not fully withstood the test of time. At present, despite the body of important results achieved in the past few years, the use of this model in some areas is somewhat deregulated; no standard protocols are available, and some critical variables that could affect experimental results are not always under control. In this article, we have focused on the use of the SCID mouse reconstituted with human mature lymphoid cells in immunological studies, and tried to enucleate, in the array of existing experimental work, some basic concepts that might favor more judicious and appropriate approaches to the use of this important experimental model.
In this study we analyzed the behavior of a CD3+ T cell subpopulation lacking CD5 antigen expression in PBMC from HIV-1-infected patients. CD3+CD5- lymphocytes were greatly increased in peripheral blood of HIV-1+ patients, accounting for 20.6 +/- 9.9% of the total CD3+ cells, compared to seronegative individuals (5.5 +/- 3.2%). In both seropositive patients and controls, CD3+CD5- cells belonged to the CD8+ compartment; they were nonactivated, TCR alpha/beta+, naive lymphocytes, and in seronegative individuals preferentially expressed NK cell-associated markers, such as CD11b, CD16, CD56, and CD57. The phenotypic profile of this subset was slightly different in seropositive patients; while TCR expression and CD45RA/RO profile were comparable, CD11b and CD16 expression was lower compared to control figures, while CD56 expression was not changed, and CD57 expression was enhanced. Functional analysis of enriched CD3+CD8+CD5- cells showed an impaired ability to proliferate in response to mitogenic and antigenic stimuli; despite their NK-like phenotype, CD3+CD8+CD5- cells did not exert any NK cytotoxic activity, and only a lectin-dependent cytotoxic potential could be evidenced in this population. These results describe a novel alteration in the lymphocytes phenotypic profile during HIV-1 infection, involving a "transitional" population, which shares some properties of the T and of the NK cell lineage.
Severe Combined Immune Deficiency mouse tumors, induced by inoculating peripheral blood mononuclear cells from 11 healthy human donors (hu-PBMC-SCID tumors), were used to analyse Epstein-Barr virus (EBV) type and strain variations. PCR analysis of EBNA 2- and EBNA 3C-specific sequences showed that EBV type A was present in SCID-mouse tumors induced by PBMC from all donors but one, while, using amplimers for a highly polymorphic region within the latent membrane protein (LMP) coding sequence, 5 different strains could be detected among the samples examined. The same LMP fragment was present in different tumors arising in the same animal, as well as in different mice injected with PBMC from any donor. Compared to B95.8 and AG876 prototype viruses, sequence analysis of LMP variants disclosed a higher homology to the latter, with 33 bp additional repetitions and a few point mutations in specific sites. This study confirms and extends previous data on the presence of a single EBV type and strain in the peripheral blood of most normal healthy subjects using the SCID-mouse system.
Intraperitoneal injection of lymphoid cells from EBV+ donors into SCID mice might provide a useful tool for studying the pathways of B-cell lymphomagenesis in man. Since previous studies showed that donor T cells greatly favor B-cell proliferation and tumor generation in this model, we addressed the host and donor factors involved in limiting or promoting lymphoma development. The number of EBV-infected B-cell precursors was crucial, since purified B lymphocytes, which alone were unable to generate tumors, underwent expansion and established tumor masses when the animals were inoculated with an EBV-containing supernatant. Host factors were critical in limiting tumor development; in vivo NK-cell removal allowed purified B cells to expand and proceed to tumors in the absence of T lymphocytes, whereas potentiation of mouse NK-cell activity prevented tumor generation in PBMC- and LCL-injected animals. The T-cell-derived factors that favor lymphomagenesis could not be identified; IL-2, IL-4, IL-6, and soluble CD23 were not able to promote B-cell expansion, and treatment of PBMC-injected mice with the relevant anti-cytokine anti-sera did not counteract lymphoma development. These experiments also showed that IL-6 plays a minor role, if any, in B-cell lymphoproliferation in this model. Our data indicate that reconstitution of SCID mice with PBMC from EBV+ donors may constitute a useful model for determining the events involved in lymphomagenesis in humans, provided that strict control of all the experimental variables is guaranteed.
We have demonstrated that interferon-alpha (IFN alpha) upregulates the epidermal growth factor receptor (EGF-R) on human epidermoid carcinoma cells. Here we report that IFN alpha induces growth inhibition and upregulation of transferrin receptor (TRF-R) on epidermoid cancer KB cells. IFN alpha does not alter TRF-R affinity for its ligand and induces a two-fold increase of TRF binding sites. IFN alpha does not modify receptor internalization and cycling. Intracellular iron levels are known to regulate TRF-R expression: we have, therefore, evaluated whether changes in the iron content could be determined by IFN alpha. Iron levels are transiently increased after addition of fresh growth medium in untreated controls but not in KB cells exposed for 48 h to IFN alpha. Iron depletion is however completely reversed 24 h later when maximal TRF-R upregulation occurs in IFN alpha-treated cells. We suggest that IFN alpha-induced iron depletion elicits a homeostatic cellular response through upregulation of TRF-R.
The effects of anti-CD3 monoclonal antibodies on cytosolic free Ca2+ concentration, [Ca2+]i, were investigated in freshly isolated lymphocytes, T cell lines, T clones and the leukemic T cell line Jurkat with three different methodologies, i.e. classical cuvette experiments, cytofluorimetry and videoimaging. With any technique, concentrations of anti-CD3 antibodies optimal for stimulation of DNA synthesis were completely ineffective at inducing early increases of [Ca2+]i in freshly isolated lymphocytes. At supraoptimal mitogenic concentrations: (i) anti-CD3 mAb induced negligible increases of [Ca2+]i when tested in suspensions of freshly isolated lymphocytes, but the response increased progressively during in vitro culturing with IL2; (ii) most, but not all, T clones, when tested in suspension, were responsive to these concentrations of anti-CD3 antibodies in terms of [Ca2+]i; (iii) using the videoimaging technique at the single cell level, it was demonstrated that the anti-CD3 antibodies induced large increases of [Ca2+]i in lymphocytes only under conditions which allowed adherence of the antibodies (and of the cells) to the glass surface. In all T cell types investigated, the [Ca2+]i increases were most often composed by multiple, asynchronous oscillations. The buffering of [Ca2+]i increases, obtained by loading the cells with membrane permeant esters of Quin-2 and Fura-2, inhibited anti-CD3 mAb induced DNA synthesis, but this appeared entirely attributable to a toxic side effect of the ester hydrolysis. The relevance of these data is discussed in terms of their methodological and functional implications for the understanding of the role of Ca2+ in mitogenic stimulation of T cells.
Groups of SCID mice were injected with different PBMC sub-populations, and established LCL cells. In about 80% of PBMC-injected animals, tumors developed in association with high levels of human Ig in mouse serum and detectable IL-6 levels. The tumors showed a histopathologic pattern reminiscent of large cell immunoblastic non-Hodgkin's lymphoma; in situ hybridization invariably evidenced EBV sequences in a minority of cells. Genotypic analysis of tumors arising in PBMC-injected mice showed the presence of different oligoclonal B cell populations in different tumor sites. Southern blot analysis disclosed the presence of both linear (replicating) and episomal (latent) EBV DNA forms; sequential analysis of LCL cells serially passaged into animals revealed the progressive selection of clonal cells with only the latent episomal form. Attempts to dissect the events underlying tumor development revealed that the presence of T cells within the injected population was essential for tumor generation; however, the putative T cell-derived factors involved are unclear, and IL-6 seems to play a minor role.
Human melanoma cells are sensitive to the lytic activity of natural killer (NK) and lymphokine-activated killer (LAK) cells in vitro. The events resulting in tumour cell killing by lymphocytic effectors have not been completely clarified, and the same target cell determinants regulating responsiveness to immune cytolysis have not yet been identified. Indeed, changes in the differentiative status of leukemia cells as well as in the expression of major histocompatibility complex (MHC) antigens have been described to modulate sensitivity to cytotoxic effectors; moreover surface expression of adhesion factors or extracellular matrix proteins by the cancer cells can promote the activation of the cytolytic effectors and has been described to correlate with tumour cell sensitivity to cytolytic cells. We reasoned that treatment with differentiation inducers could modulate melanoma cell sensitivity to NK and LAK cells. The present study demonstrates that human melanoma GLL-19 cells, when treated with the phorbol diester phorbol 12-myristate 13-acetate (PMA) in vitro, undergo growth inhibition and neuron-like differentiation. Moreover, PMA treatment induces an evident inhibition of GLL-19 cell sensitivity to NK- and LAK-mediated cytotoxicity. GLL-19 cells express constitutively MHC class I antigens. PMA treatment, however, does not modify the expression of MHC class I and class II DR antigens in human melanoma GLL-19 cells. We have finally evaluated the effects of PMA on the expression at the cell surface of adhesion factors such as ICAM-1, and extracellular matrix proteins such as collagen IV, laminin and fibronectin; we have also studied the expression of the integrin vitronectin receptor, a membrane receptor for adhesive proteins. While adhesion factors and extracellular matrix proteins appear to play an important role in the interaction between immune effector and tumour target, it can be supposed that the modulation of such membrane-associated proteins or glycoproteins induces NK and LAK resistance in cancer cells. We indeed found that PMA treatment induced in GLL-19 a marked reduction of membrane expression of collagen IV and ICAM-1; moreover PMA reduced the cell membrane expression of the integrin vitronectin receptor. On the other hand, membrane expression of fibronectin and laminin was not affected by PMA. These data indicate that the acquisition of a NK- and LAK-resistant phenotype by GLL-19 cells occurs together with cell differentiation, down-regulation of membrane expression of collagen IV, ICAM-1 and vitronectin receptor, but in the absence of changes in MHC antigens.
Sixty patients with type I diabetes mellitus underwent an ergometric stress test (EST) to evaluate the relationship between cardiac autonomic neuropathy (CAN) and hemodynamic changes during EST. All patients were divided into 2 groups: in the Group A were included 26 patients (mean age 43 +/- 9 years) with impairment of 2 or more autonomic tests according to Ewing (patients with CAN) and in the Group B were included 34 patients (mean age 38 +/- 13 years) without CAN. The EST was symptom-limited and performed with load increases of 25 W every 3 min. No positive EST were observed in both groups. Heart rate (HR) at rest and systolic blood pressure (SBP) at maximum common workload were significantly higher in Group A than in Group B. Moreover, a significant linear correlation was found between a CAN score and SBP x HR product at rest and at maximal workload. These findings are correlated with increased sympathetic activity due to a parasympathetic impairment. The data show the relationship between hemodynamic changes during EST and the Ewing test used in the diagnosis of CAN.
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Common bile duct (CBD) diameter was measured with ultrasonography in 396 patients (131 had previous cholecystectomy) before and 40 minutes after the ingestion of a fatty meal. CBD diameter reduced in 177 cases, remained unchanged in 175, increased in 44. The increasing of CBD diameter always means obstructive choledochal pathology, caused by stones or other pathologic conditions. Caliber reduction or other pathologic conditions. Caliber reduction is physiologic. When CBD remains unchanged, in 10% of the cases there are stones in the duct.