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ABSTRACT: The great majority of chronic leg ulcers are caused by disturbances of venous and arterial circulation in the lower extremities. Diagnostics and treatment of ulcers require multiprofessional collaboration. The cornerstone of the treatment is conservative treatment intervening in the underlying causes of the ulceration. If the ulcer is large or recovery does not take place with appropriate conservative therapy, reconstructive surgery may come into question, i.e. surgical excision of the ulcer and its covering with a skin graft.
Duodecim; lääketieteellinen aikakauskirja 01/2012; 128(19):2007-14.
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ABSTRACT: Endostatin is an antiangiogenic growth factor. Together with proangiogenic growth factors it acts to shape the developing vasculature. Dysregulation of angiogenesis is a component in the pathogenesis of bronchopulmonary dysplasia.
Our goal was to study whether the concentration of circulating endostatin at birth is associated with the development of bronchopulmonary dysplasia in very low birth weight infants.
Endostatin concentration was measured in cord plasma from 92 very low birth weight infants (gestational age < 32 weeks; birth weight < 1500 g) and 48 healthy term infants (gestational age > 37 weeks; birth weight > 2500 g).
Endostatin concentration in very low birth weight infants was lower than in healthy term infants. Within the very low birth weight group no correlation existed between endostatin concentration and gestational age or relative birth weight. Very low birth weight infants who subsequently developed bronchopulmonary dysplasia had higher cord endostatin than those who did not. Higher endostatin concentration was associated with higher odds for bronchopulmonary dysplasia. Adjusted for gestational age, the odds for bronchopulmonary dysplasia were higher.
Circulating endostatin in term infants was higher than in very low birth weight infants, suggesting a temporal pattern for fetal endostatin concentration. In very low birth weight infants a high concentration of circulating endostatin at birth is associated with the subsequent development of bronchopulmonary dysplasia.
PEDIATRICS 05/2009; 123(4):1142-6. · 4.47 Impact Factor
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ABSTRACT: We examined the pulmonary expression of 2 proangiogenic factors, namely, placental growth factor and vascular endothelial growth factor receptor-2, during lung development and acute and chronic lung injury in newborn infants.
Six groups were included in an immunohistochemical study of placental growth factor and vascular endothelial growth factor receptor-2, that is, 9 fetuses, 4 preterm and 8 term infants without lung injury who died soon after birth, 5 preterm infants with respiratory distress syndrome of <2 days and 7 with respiratory distress syndrome of >10 days, and 6 with bronchopulmonary dysplasia. Placental growth factor concentrations in tracheal aspirate fluid were measured in 70 samples from 20 preterm infants during the first postnatal week.
In immunohistochemical analyses, placental growth factor staining was seen in bronchial epithelium and macrophages in all groups. Distal airway epithelium positivity was observed mostly in fetuses and in preterm infants who died soon after birth. Vascular endothelial growth factor receptor-2 staining was seen in vascular endothelium in all groups and also in lymphatic endothelium in fetuses. Vascular endothelial growth factor receptor-2 staining in arterial endothelium was associated with higher and staining in venous endothelium with lower gestational age. In capillaries, less vascular endothelial growth factor receptor-2 staining was seen in bronchopulmonary dysplasia. The mean placental growth factor protein concentration in tracheal aspirate fluid during the first postnatal week was 0.64 +/- 0.42 pg/mL per IgA-secretory component unit. Concentrations during the first postnatal week were stable. Lower placental growth factor concentrations correlated with chorioamnionitis and lactosyl ceramide positivity.
The vascular endothelial growth factor receptor-2 staining pattern seems to reflect ongoing differentiation and activity of different endothelia. Lower vascular endothelial growth factor receptor-2 expression in capillary endothelium in bronchopulmonary dysplasia might be a reflection of the dysregulation of vascular development that is characteristic of bronchopulmonary dysplasia.
PEDIATRICS 08/2008; 122(2):340-6. · 4.47 Impact Factor
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ABSTRACT: Endostatin is a potent angiogenesis inhibitor. Angiogenesis is central for the development of the human lung. The role of endostatin in the development of the human lung and its connection to chronic lung disease remain unclear. We set out to study the role of endostatin in the developing human lung and in acute and chronic lung injury in the preterm infant.
Nine fetuses, 14 control neonates without primary lung disease, 14 preterm infants with respiratory distress syndrome, and 8 infants with bronchopulmonary dysplasia were included in the immunohistochemistry study. Tracheal aspirate-fluid samples of intubated very low birth weight infants during postnatal weeks 1 through 5 were analyzed with enzyme-linked immunosorbent assay.
Endothelial cell staining was positive for endostatin in all 45 samples. Staining of epithelial cells (cuboidal, bronchiolar, and alveolar) was seen mostly in fetuses, as well as in infants with late respiratory distress syndrome and bronchopulmonary dysplasia. Staining in alveolar macrophages was most abundant in infants with late respiratory distress syndrome and bronchopulmonary dysplasia. Endostatin was expressed consistently in tracheal aspirate fluid, being highest during the first postnatal day. Higher endostatin concentrations correlated with parameters reflecting lower lung maturity.
The pattern of pulmonary endostatin protein expression in immunohistochemistry and consistent endostatin protein appearance in tracheal aspirate fluid in human preterm infants indicate a role in the physiologic development of the lung. Preterm birth influences pulmonary endostatin protein expression, which may alter normal lung development and response to lung injury.
PEDIATRICS 02/2007; 119(1):e241-6. · 4.47 Impact Factor
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ABSTRACT: In mice, vascular endothelial growth factor-C (VEGF-C) plays an important role in development of the lymphatic system and in pathogenesis of pulmonary inflammation. Its role in development of the lymphatic system in human lung and in lung injury in newborns remains unclear.
We studied the role of VEGF-C in developing human lung, and in acute and chronic lung injury in preterm infants.
Included in the immunohistochemistry study were 10 fetuses, 15 control neonates without primary lung disease, 15 preterm infants with respiratory distress syndrome, and 8 infants with bronchopulmonary dysplasia. Tracheal aspirate fluid samples of intubated very-low-birth-weight infants during Postnatal Weeks 1-5 were analyzed with ELISA.
Bronchiolar staining for VEGF-C was observed in all 48 samples. Alveolar epithelial staining was seen in most fetuses (8/10). In addition, staining was observed in alveolar macrophages in bronchopulmonary dysplasia (4/8), and late respiratory distress syndrome (2/7). VEGF receptor-3 (VEGFR-3) staining was observed in lymphatic endothelium adjacent to vascular endothelium. VEGF-C was expressed consistently in tracheal aspirate fluid, being highest during the first 2 postnatal days. Antenatal administration of glucocorticoids was associated with higher VEGF-C in tracheal aspirate fluid.
The pattern of pulmonary VEGF-C and VEGFR-3 protein expression and consistent VEGF-C protein appearance in tracheal aspirate fluid in human preterm infants indicate a role for VEGF-C in the physiologic development of the lymphatic system of the lung.
American Journal of Respiratory and Critical Care Medicine 09/2006; 174(3):326-30. · 11.08 Impact Factor
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ABSTRACT: Merkel cell carcinoma (MCC) is a highly malignant neuroendocrine skin tumor. The typical course of MCC is rapid progression of the primary tumor and metastatic dissemination to the regional lymph nodes. Thus far, no biological, prognostic marker has been established for this aggressive neoplasm. Cyclooxygenase-2 (Cox-2) is undetectable in most normal tissues, but it is induced in various cell types by inflammation and carcinogenesis. Although the expression and function of Cox-2 have been studied extensively in several carcinomas, little is known about Cox-2 expression in neuroendocrine carcinomas. The aim of the present report was to study Cox-2 expression in MCC and find out whether this expression correlates with outcome.
Immunohistochemical analysis for Cox-2 was performed on 22 primary MCC samples.
Almost 70% of the samples showed positive staining. Protein expression of Cox-2 was sparse and low in intensity. We found a tendency for enhanced Cox-2 expression in tumors located in sun-exposed areas. Cox-2 expression had no significant statistical correlation with clinical parameters.
MCC expresses Cox-2 in low levels, and the expression did not prove to be a prognostic factor. Furthermore, the low expression suggests that the primary treatment option for MCC is not therapeutic inhibition of Cox-2.
Journal of Cutaneous Pathology 02/2005; 32(1):55-8. · 1.56 Impact Factor
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ABSTRACT: We hypothesize that IGF-1 and IGF-1R proteins are upregulated in lung epithelia and fibroblasts in RDS compared to normal development, and are further upregulated in BPD. We used immunohistochemistry to evaluate IGF-1 and IGF-R expression in lungs from autopsies of human stillbirths and RDS and BPD patients. IGF-1 and IGF-R immunostaining were present in fetal, RDS, and BPD lungs. In RDS, IGF-1 was present in alveolar epithelium and prominent in columnar and cuboidal airway epithelia. In BPD lungs, immunostaining was intensely increased in both airway and alveolar epithelia and in mesenchyme. The immunostaining index in bronchial epithelial cells and peribronchial myofibroblasts was significantly higher in BPD compared to RDS. IGF-1R expression was minimal in fetal lung and found mainly in mesenchyme. IGF-1R was increased in mesenchyme in RDS. In BPD it was especially increased in peribronchial and perialveolar mesenchyme. Immunostaining index for IGF-1R in epithelial cells and peribronchial myofibroblasts was increased in BPD compared to RDS. IGF-1 and IGF-R expression is low during fetal development, but is acutely upregulated in RDS, and persists with further upregulation in BPD.
Pediatric Pulmonology 03/2004; 37(2):128-36. · 2.53 Impact Factor
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American Journal of Respiratory and Critical Care Medicine 09/2003; 168(4):501; author reply 501-2. · 11.08 Impact Factor
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ABSTRACT: Hepatocyte growth factor (HGF) participates in normal lung development and in regeneration after lung injury in animals. We studied the role of HGF during the perinatal period and in the development of bronchopulmonary dysplasia (BPD).
HGF was measured in 172 tracheal aspirate fluid samples (TAF) from 17 preterm infants in whom BPD subsequently developed (gestational age, 27.2+/-1.7 weeks; body weight, 828+/-210 g) and from 15 who survived without BPD (gestational age, 26.8+/-1.9 weeks; body weight, 994+/-265 g) during the first 2 postnatal weeks.
Infants with subsequent development of BPD had lower HGF in TAF (45+/-9 pg/mL per IgA-sc) than those surviving without BPD (102+/-32 pg/mL per IgA-sc; P=.028). Lower HGF in TAF were seen in infants with more severe acute respiratory distress as defined as requirement for surfactant therapy (50+/-14 vs 146+/-50 pg/mL per IgA-sc in infants requiring no surfactant; P=.0001), for higher number of surfactant doses (r=-0.16, P=.06), and for mechanical ventilation >1 week (167+/-51 vs 51+/-14 pg/mL per IgA-sc in infants intubated <1 week; P=.0012).
These data show an association between lower HGF concentration in TAF and more severe lung disease in human preterm infants in the early neonatal period.
Journal of Pediatrics 09/2003; 143(2):199-202. · 4.11 Impact Factor
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ABSTRACT: We evaluated the concentrations of vascular endothelial growth factor (VEGF) and angiogenin in the umbilical cord blood from 14 fetuses with erythroblastosis or alloimmune thrombocytopenia and at birth from 28 preterm fetuses, from 42 healthy term fetuses, and from 24 term fetuses born to mothers with insulin-treated diabetes. A correlation appeared between VEGF and angiogenin levels (r = 0.44, p = 0.038). The gestational age correlated with both VEGF (r = 0.38, p = 0.0008) and angiogenin levels (r = 0.80, p = 0.0001). The concentration of VEGF was lower in fetuses born to mothers with insulin-treated diabetes than in the healthy term fetuses (p = 0.0028), but this difference was absent for angiogenin (p > 0.05). In conclusion, in umbilical cord plasma, a developmental increase was evident in concentrations of VEGF and angiogenin during the last trimester of gestation. That the umbilical cord VEGF level was lower in term fetuses born to mothers with diabetes than in term fetuses of healthy mothers may be associated with an aberrant fetal vascular development in diabetic pregnancies.
Biology of the Neonate 01/2003; 84(4):287-92. · 1.90 Impact Factor
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ABSTRACT: To evaluate in preterm infants the effect of dexamethasone on hepatocyte growth factor (HGF), an epithelial cell mitogen, and on vascular endothelial growth factor (VEGF), an endothelial cell mitogen, in tracheal aspirate fluid (TAF).
Thirty preterm infants (birth weight: 1000-1500 g) with respiratory distress syndrome were randomized to receive dexamethasone or to serve as control subjects. Dexamethasone was started at the age of 12 to 24 hours at a dose of 0.5 mg/kg/d for 2 days and 0.25 mg/kg/d for the subsequent 2 days. HGF and VEGF levels were examined from TAF samples during the first postnatal week. For eliminating the effect of dilution, the concentration of the secretory component of immunoglobulin A was determined. Student t test, 1-way analysis of variance, chi2, and simple regression analysis were used for statistical analysis.
Mean HGF concentrations were similar in the dexamethasone and control groups on days 1 to 2, but the dexamethasone group had a lower mean HGF concentration on days 3 to 4 and 5 to 7. In contrast, no differences existed in mean VEGF levels between the dexamethasone and control groups.
In preterm infants who received early postnatal dexamethasone, reduced levels of HGF were seen in tracheal aspirates. This reduction may participate in the suppressive effects of dexamethasone on lung development.
PEDIATRICS 11/2002; 110(4):768-71. · 4.47 Impact Factor
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ABSTRACT: Prostacyclin (PGI(2)) and thromboxane A(2) (TxA(2)) may take part in lung pathology; high concentrations of PGI(2) may protect newborn rabbits against hyperoxic lung injury, and TxA(2) may participate in the development of bronchopulmonary dysplasia (BPD). Aims: To examine in small preterm infants, the relationship between pulmonary PGI(2) and TxA(2) and respiratory distress during the early postnatal period.
The stable metabolite of prostacyclin, 6-keto-prostaglandinF(1 alpha), and that of thromboxane A(2), thromboxane B(2), were quantified by radioimmunoassays in 284 samples of tracheal aspirates from 48 infants (GA: 27.4+/-2.1 week, BW 959+/-334 g) during the first 12 postnatal days.
Mean concentration of 6-keto-prostaglandinF(1 alpha) was 414+/-31 pg/ml (mean+/-S.E.M.), and of thromboxane B(2) was 418+/-37 pg/ml. Correlations existed between 6-keto-prostaglandinF(1 alpha) and gestational age, birth weight, and the initial arterial-alveolar oxygenation ratio. Negative correlations existed between 6-keto-prostaglandinF(1 alpha) and both mean inspiratory oxygen and duration of mechanical ventilation. Indomethacin treatment was associated with lower pulmonary 6-keto-prostaglandinF(1 alpha), but not with lower TxB(2). Thromboxane B(2) correlated positively with gestational age, birth weight, and initial arterial-alveolar oxygenation ratio, and inversely with duration of mechanical ventilation.
In preterm infants, higher pulmonary 6-keto-prostaglandinF(1 alpha) was associated with less severe respiratory distress and with maturity, whereas thromboxane B(2) was associated more strongly with maturity than with respiratory distress.
Early Human Development 05/2002; 67(1-2):11-8. · 2.05 Impact Factor
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ABSTRACT: Cyclooxygenase-2 (Cox-2) is expressed by several types of epithelial malignancies, i.e., carcinomas, and inhibition of Cox-2 may have a therapeutic role in chemoprevention and treatment of cancer. The role of Cox-2 in non-epithelial malignancies, however, is unclear.
We investigated, by immuno- histochemistry, the expression of Cox-2 in 103 human soft-tissue sarcomas.
All 10 biphasic synovial sarcomas were positive for Cox-2, but positivity was observable only in the epithelial component of these tumours. Excluding sarcomas with epithelial differentation, uniform staining of the tumour was observed in only 2 samples. In addition, positivity for Cox-2 appeared in tumour cells in only 18 samples around necrotic areas.
In human soft-tissue sarcomas, Cox-2 expression seems to be associated with epithelial differentation and, in some types of sarcomas, to be expressed in otherwise negative tumours at sites of necrosis.
Anticancer research 25(4):2669-74. · 1.73 Impact Factor
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ABSTRACT: The aim of this study was to examine the expression of vascular endothelial growth factor receptor-2 (VEGFR-2) in Merkel cell carcinoma (MCC) and to correlate the expression with tumour growth and the development of metastasis.
The study included 21 patients treated for MCC at Helsinki University Hospital, Helsinki, Finland between 1987 and 2003. The VEGFR-2 expression was studied by immunohistochemistry. The correlations between the quantitative expression of VEGFR-2 and tumour size and metastatic dissemination were analyzed statistically.
VEGFR-2 was expressed in 91% of the large (> or =2 cm) and 70% of the small (<2 cm) tumours. There was a stronger positive correlation between expression of VEGFR-2 and tumour size than between VEGFR-2 and metastatic potential.
A correlation between the expression of pro-angiogenic marker and tumour size was established. Our results indicate that inhibiting angiogenesis could be a treatment option for MCC. The role of neovascularization in the metastatic process in MCC remains to be determined.
Anticancer research 27(4C):2587-9. · 1.73 Impact Factor
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ABSTRACT: The aim of this study was to examine the expression of endostatin in Merkel cell carcinoma (MCC) and to correlate the expression with tumour growth and the development of metastasis.
The study comprised 19 patients treated for MCC at the Helsinki University Hospital, Helsinki, Finland between 1987 and 2003. Endostatin expression was studied by immunohistochemistry. The correlations between the quantitative expression of endostatin and tumour parameters were analysed statistically.
The expression of endostatin was documented in only 40% of the samples. Endostatin correlated negatively with tumour size, and was expressed in 30% of the large and 56% of the small tumours. There was no difference in expression between tumours expanding to metastases and tumours with more indolent behaviour. The simultaneous expression of vascular endothelial growth factor receptor-2 and endostatin was distinguished in small-sized tumours.
This study showed a correlation between endostatin expression and small tumour size in Merkel cell carcinoma. This finding was further confirmed by the finding that tumours positive for VEGFR-2, but not for endostatin, seemed to be larger than tumours that showed simultaneous expression of VEGFR-2 and endostatin.
Anticancer research 27(4C):2583-6. · 1.73 Impact Factor
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Patrik. Lassus
