Ewa Andrzejewska

LOCAL SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN INFANTILE HEMANGIOMA: INTRIGUING MECHANISM OF ENDOTHELIAL GROWTH

UNLABELLEDnThe pathogenesis of hemangiomas still remains poorly understood. Dysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of our study was to determine the peripheral and local serum levels of VEGF in patients with hemangiomas and vascular malformations.nnnMATERIAL AND METHODSnThe study group consisted of 52 children with infantile hemangioma (33 with proliferative lesions, 19 with involuting lesions), 14 children with vascular malformations and 36 healthy children. VEGF serum levels were analyzed by an ELISA assay and the values between the groups were compared.nnnRESULTSnThe serum peripheral VEGF concentrations in children with proliferative hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and controls. There was no correlation between the measured cytokine level, hemangioma size, and the age of the patients. The local serum VEGF levels in 29 children with hemangiomas were distinctly lower than in the peripheral blood, both in 20 proliferating hemangiomas (p<0.0001) and 9 involuting ones (p=0.007); and the difference between females and males was non-significant (NS p=0.06).nnnCONCLUSIONSn(1) VEGF serum levels vary in the different phases of hemangioma growth and may help to distinguish hemangiomas from vascular malformations; (2) obtained local results may support the intrinsic theory of endothelial cell proliferation in hemangiomas.

SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND BASIC FIBROBLASTIC GROWTH FACTOR IN CHILDREN WITH HEMANGIOMAS AND VASCULAR MALFORMATIONS--PRELIMINARY REPORT

Abstract:u2003 Impaired balance between proangiogenic and antiangiogenic factors has been implicated in the development of hemangiomas. Elevated vascular endothelial growth factor serum levels and basic fibroblastic growth factor urine levels in patients with proliferating hemangiomas were reported. However, whether these growth factors can be used for the differential diagnosis of vascular anomalies or assessment of the clinical course of hemangiomas has yet to be determined. We report here our preliminary results of serum vascular endothelial growth factor and basic fibroblastic growth factor levels as an aid in the diagnosis of hemangiomas and in the follow up of patients with this lesion. Twenty two children with infantile hemangioma (13 with proliferating hemangiomas, nine with involuting lesions), five children with vascular malformations, and 25 healthy children study group. Vascular endothelial growth factor and basic fibroblastic growth factor serum levels were analyzed by an ELISA assay. The serum vascular endothelial growth factor concentrations in children with proliferating hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and healthy patients. The serum basic fibroblastic growth factor concentrations were low and similar in all patients with no statistical correlation between study groups. We concluded that (i) ELISA can easily determine vascular endothelial growth factor concentrations in different phases of hemangioma growth and help distinguishing them from vascular malformations. (ii) A potential role for vascular endothelial growth factor in the pathophysiology of hemangiomas is probable.

New measuring device for estimating the pressure under compression garments

Purpose – This paper aims to describe new measuring device designed for measuring the pressure exerted by textile products used in healing therapy of hypertrophic scars. The testing device called “Textilpress” has been used for verification of the usually used method of designing and manufacturing ready‐made compression garment products.Design/methodology/approach – The pressure measurement, realized by use of the “Textilpress” device, is an indirect measuring method, which is based on the Laplace Law. The investigations described in this paper concern the pressure measuring under textile bands placed on the models representing selected parts of the human body with pre‐set circumferences. For this purpose, rigid cylinders were prepared, covered by a layer of neoprene which simulated the susceptibility of human skin.Findings – The investigations described in this paper indicate that the “Textilpress” test‐device may be used for pressure measuring exerted by compression bands on the cylinder surface. In ord...

Serum levels of basic fibroblastic growth factor (bFGF) in children with vascular anomalies: Another insight into endothelial growth

OBJECTIVESnDysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of the study was to determine the peripheral and local serum levels of bFGF in patients with hemangiomas and vascular malformations (VM).nnnDESIGN AND METHODSnThe study group consisted of 52 children with infantile hemangioma, 14 with VM and 36 healthy patients. bFGF serum levels were analyzed by an ELISA assay. Urinary bFGF was determined in 11 individuals with hemangioma.nnnRESULTSnThe serum peripheral bFGF concentrations in children with proliferating hemangiomas were lower than in healthy controls (p=0,03). There was no correlation between the measured cytokine level and hemangioma size, as well as patients age. The serum local bFGF levels in 29 children with hemangiomas were higher than in the peripheral blood (p=0.022). Urinary bFGF in hemangioma patients did not differ statistically from healthy controls.nnnCONCLUSIONSn(1) Determination of bFGF serum levels is not helpful in differentiating the phases of hemangioma growth and distinguishing hemangiomas from VM; (2) serum levels of bFGF cannot distinguish between extrinsic and intrinsic theories of endothelial cell proliferation in hemangiomas.

Molecular and immunohistochemical expression of apoptotic proteins Bax, Bcl-2 and Caspase 3 in infantile hemangioma tissues as an effect of propranolol treatment

BACKGROUNDnInfantile hemangiomas (IHs) are the most common benign tumors of childhood. They are characterized by a unique clinical course with two phases, proliferation and involution, which are followed by regression. The therapy of infantile hemangiomas was revolutionized in 2008 by the introduction of propranolol, however, the mechanism of its influence on hemangiomas remains unclear.nnnMETHODSnThe study included 71 patients with IHs, 27 of whom were treated with propranolol while the remaining 44 were used as a comparative group. The expression of Bcl-2, Bax and Caspase3 was determined with immunohistochemistry and mRNA of Bax, Bcl-2 and Caspase3 were assessed with the use of RT-PCR.nnnRESULTSnBoth methods revealed a statistically significant decrease in Bcl-2 expression and an increase in Bax in IHs tissues after propranolol treatment.nnnCONCLUSIONSnThe results obtained for Bax and Bcl-2 proteins may indicate a link between the effect of propranolol and apoptosis. Higher Bax and lower Bcl-2 expression in the propranolol treated group indicates a strong pro- apoptotic action countering any anti-apoptotic activity; apoptosis was indicted in IH tissue as a potential result of propranolol treatment, with potential clinical impact in other tumors.

Serum and tissue profile of VEGF and its receptors VGFR1/R2 in children with infantile hemangiomas on systemic propranolol treatment

UNLABELLEDnIn the last few years propranolol has revolutionized infantile hemangioma therapy. This nonselective β bloker has been proven to be safe and effective but the molecular bases of its actions remain unclear. One of debated theories holds that propranolol may inhibit angiogenesis and induce apoptosis. To investigate this claim, this study aims to analyze the serum and tissue profiles of VEGF and VEGRR1/2 in patients treated with propranolol.nnnMATERIALS AND METHODSnTo assess the expression if VEGF and VEGRR1/2 we used three independent methods. First we analyzed serum VEGF levels in 50 children with IH before and 3 months after the therapy using ELISA test (I.). Then we used immunohistochemistry to evaluate tissue expression of VEGF and VEGFR1/2 in IH treated (n=27) and not treated (n=45) with propranolol (II.). Finally we assessed mRNA of VEGF and VEGFR1/2 in the same patients as in part II (III.).nnnRESULTSn(I) There was no distinct decrease of VEGF level in children with IH after propranolol treatment. (II) We found no significant difference in VEGFR1 and VEGFR2 expression in hemangiomas from the study and control group. The expression of VEGF was even higher than before therapy. (III) VEGF and VEGFR1 mRNA expression was significantly lower in IH tissue after propranolol treatment compared to those without treatment. VEGFR2 demonstrated no differences in expression between the two groups.nnnCONCLUSIONSnThe obtained results show distinct discrepancies between in vitro and clinical studies as well as among different methods used for analyzing the same phenomenon. Only VEGF and VEGFR1 expression in mRNA studies may prove the proposed theory of antiangiogenic properties of propranolol. Other results do not confirm it and remain inconsistent with the fantastic clinical response to this medication.

Soluble receptors for vascular endothelial growth factor (sVEGFR1/sVEGFR2) in infantile hemangioma

Vascular endothelial growth factor (VEGF) and its receptors were postulated to be involved in pathogenesis of infantile hemangioma. The aim of this study was to determine the serum levels of VEGF and soluble VEGF receptors (sVEGFR1/sVEGFR2) in children with hemangiomas. Materials and methods: Thirty-eight children with infantile hemangiomas (25 proliferating, 13 involuting) and 34 healthy children were included in the study. sVEGFR1 and sVEGFR2 serum levels in peripheral blood and in vascular tumors were determined with ELISA test. Results: sVEGFR1 serum levels were slightly lower in hemangioma patients (p = 0.049). No significant differences in sVEGFR2 levels were observed in any study group. VEGF levels did differ significantly, with median level being 364.05 pg/ml in hemangioma patients and 107.40 pg/ml in the control group (p < 0.0001). Conclusions: The obtained results suggest that VEGF is involved in hemangioma angiogenesis but that soluble VEGFRs marginally influence this process. Lower serum levels of sVEGFR1 in hemangioma patients indicate the possible dysregulation between VEGFR1 and VEGFR2 receptors.

Fingertip injuries in children treated in Department of Pediatric Surgery and Oncology in the years 2008-2010.

BACKGROUNDnFingertip injuries are the most common hand injuries in children seeking medical advice at trauma care centres. Most cases are treated conservatively and hospitalisation is not necessary. However, surgery under general anaesthesia is often required on account of severity of the injuries and the patients young age. The aim of the paper is to discuss a series of patients treated in the Department of Paediatric Surgery and Oncology between 2008 and 2010, and present the problems associated with surgical care in fingertip injuries in children.nnnMATERIAL AND METHODSnA total of 76 children were treated in the Department of Pediatric Surgery and Oncology between 2008 and 2010 because of fingertip injuries. This group is estimated to represent approx. 10% of all patients admitted to the Emergency Unit. Fingertip injuries were treated with situation sutures, V-Y-plasty, suturing back the amputated fingertip and by suturing into thenar skin. Data were extracted from medical files and presented as percentages.nnnRESULTSnThere were 50 boys in the group of 76 children (65.79%). Mean age was 7 years. Most of the patients were children aged 1 to 5 years (36 patients, 47.37%). In 45 children (59%), the right hand was injured. Injury to fingers responsible for the pincer grasp occurred in 29 children (38.16%).nnnCONCLUSIONSnFingertip injuries are among the most common injuries in children and preservation of the hands motor abilities depends on thorough surgical care. Most children with fingertip injuries are treated in Emergency Units and only 10% of patients need surgery under general anaesthesia after hospital admission. A number of surgical techniques can be used in the management of fingertip injuries in children. These techniques represent adaptations of methods used in adults. A model for the evaluation of severity and management of fingertip injuries in children should be established.

The Role of Ultrasound Imaging of Callus Formation in the Treatment of Long Bone Fractures in Children.

Summary Background In the process of diagnosis and treatment of fractures, an X-ray study is typically performed. In modern medicine very important is the development of new diagnostic methods without adverse effects on the body. One of such techniques is ultrasound imaging. It has a high value in imaging most areas of the body, including the musculoskeletal system. Reports on the use of ultrasound in the evaluation of the callus are rare and this could be a method equivalent to or even better than standard radiographs. The aim of the study was to analyze the correlation of ultrasound with radiographs in imaging of callus formation after fractures of long bones in children and to analyze the correlation of vascular resistance index (RI) and the degree of vascularization of the callus with a subjective radiological assessment of the bone union quality. Material/Methods The prospective study was planned to qualify 50 children treated for long bones fractures of the arm, forearm, thigh and lower leg. Ultrasound diagnosis was carried out using a Philips iU22 camera equipped with a linear probe with 17-5-MHz resolution and MSK Superficial program. During ultrasound examination measurements of the callus were performed. Using the Power Doppler callus vascularity was visualized and vascular resistance index (RI) was measured. The same measurements were made within the corresponding area of the healthy limb. The results obtained by ultrasound were compared with radiograph measurements and with the subjective assessment of the callus quality. Results Preliminary results were developed on a group of 24 patients, where 28 fractured bones and 28 corresponding healthy bones were examined. Fifteen boys and 9 girls participated in the study. The average age at injury was, respectively, 11 and 9 years. In both groups fractures without displacement were the most frequent. A similar frequency was observed in fractures requiring reposition and subperiosteal fractures. In contrast, fractures with a slight displacement of the fragments, were 3 times more common in girls. Statistical analysis of the measurements of length and width of the callus demonstrated that the differences between results obtained in the ultrasound in comparison with X-rays were not statistically significant. Moreover, preliminary results showed a significantly higher degree of vascularization of the callus than of the healthy periosteum. Conclusions Preliminary results indicate the high efficacy of ultrasound in the evaluation of callus formation after fractures of long bones in children and the possibility of its alternative use to X-ray examinations.

Tissue and serum mRNA profile of MMPs-2/9 as a potential novel biomarker for the most individual approach in infantile hemangiomas and cancer disease

Propranolol is a widely-known beta-blocker approved for treating infantile hemangiomas (IH). The mechanisms behind the spectacular IH involution after propranolol treatment remain unclear. Recently, there is strong evidence of overexpression of numerous angiogenic factors in IH tissues, and it is reported that propranolol influences their pathways. However, a number of MMPs studies is highly limited. Here, for the first time, we propose a comprehensive approach by analyzing the expression levels of metalloproteinases-2/9 (MMPs-2/9) and tissue metalloproteinase inhibitor-2 (TIMP-2) in vivo on both, molecular and immunohistochemical levels, and in both, IH tissues and in the serum of IH patients, and relates the obtained results to the tumors biology and systemic propranolol treatment.nnnMATERIAL AND METHODSnMMPs-2/9 and TIMP-2 were analyzed in 71 IH tissue samples using immunohistochemistry and real-time PCR, and in 50 serum samples of IH patients by ELISA.nnnRESULTSnSignificantly lower MMPs-2/9 and higher TIMP-2 levels were observed in IH tissues on the mRNA level as well as lower serum MMP-2 concentration among the treated individuals.nnnCONCLUSIONnMMPs-2/9 and TIMP-2 are both involved in the biology of IH and the propranolol pathways enabling their antiangiogenic properties. The most reliable method of IH examination appears to be direct MMPs-2/9 mRNA evaluation in tumor tissue; and MMP-2 evaluation in patients serum is a valuable complement to it. Tissue and serum mRNA MMPs assessment may represent a suitable novel biomarker identifying tumor progression and involution processes with potential clinical impact in IH as well as in cancer disease.