Przemysław Pawłowski, Mirosława Urban, Anna Stasiak-Barmuta
Background: Type 1 diabetes is mediated by autoreactive - T lymphocytes recognizing pancreatic islet cell antigens. CD28/CTLA-4 costimulatory molecules participate in the transduction of the necessary signal in T lymphocytes proliferation and play an important role in the development of autoimmunological process.
Objectives: The purpose of this study was: to evaluate whether the expression of CD28, CTLA-4 molecules on peripheral blood T lymphocytes alters in the course of disease -- diabetes lasting less than 5 years and over 5 years; to assess a relationship between the percentage of CD28, CTLA-4 on T cells and the evolution of vascular complications (microalbuminuria, arterial hypertension, diabetic retinopathy).
Material and methods: The study was carried out in three groups of subjects - 60 children (aged 9-20) with diagnosed type 1 diabetes: (a) (20 n) with the disease lasting >5 years, (b) (20 n) with type 1 diabetes lasting >5 years without vascular complications, (c) (20 n) with type 1 diabetes and vascular complications (microalbuminuria, arterial hypertension, diabetic retinopathy). The control group consisted of 20 healthy volunteers (aged 6-17). The expression of adhesion molecules has been evaluated by using three-color flow cytometry (Coulter EPICS XL). HbA1c concentration has been analysed by liquid chromatography technique HPLC-Variant (Bio-Rad).
Results: In the study, the superficial expression of CTLA-4 receptor on T lymphocytes was enhanced in children with diabetes lasting <5 years (p<0.005) and over 5 years without vascular complications (p<0.01) versus healthy patients and tend to normalize in the presence of developing vascular complications In contrast, the expression of costimulatory molecule CD28 was decreased in children with type 1 diabetes lasting <5 years (p<0.05) as well as in children with developing vascular complications (p<0.01) versus the control group.
{"title":"[Surface expression of costimulatory molecules CD28/CTLA-4 on peripheral blood T lymphocytes in the course of type 1 diabetes mellitus in children and adolescents].","authors":"Przemysław Pawłowski, Mirosława Urban, Anna Stasiak-Barmuta","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Type 1 diabetes is mediated by autoreactive - T lymphocytes recognizing pancreatic islet cell antigens. CD28/CTLA-4 costimulatory molecules participate in the transduction of the necessary signal in T lymphocytes proliferation and play an important role in the development of autoimmunological process.</p><p><strong>Objectives: </strong>The purpose of this study was: to evaluate whether the expression of CD28, CTLA-4 molecules on peripheral blood T lymphocytes alters in the course of disease -- diabetes lasting less than 5 years and over 5 years; to assess a relationship between the percentage of CD28, CTLA-4 on T cells and the evolution of vascular complications (microalbuminuria, arterial hypertension, diabetic retinopathy).</p><p><strong>Material and methods: </strong>The study was carried out in three groups of subjects - 60 children (aged 9-20) with diagnosed type 1 diabetes: (a) (20 n) with the disease lasting >5 years, (b) (20 n) with type 1 diabetes lasting >5 years without vascular complications, (c) (20 n) with type 1 diabetes and vascular complications (microalbuminuria, arterial hypertension, diabetic retinopathy). The control group consisted of 20 healthy volunteers (aged 6-17). The expression of adhesion molecules has been evaluated by using three-color flow cytometry (Coulter EPICS XL). HbA1c concentration has been analysed by liquid chromatography technique HPLC-Variant (Bio-Rad).</p><p><strong>Results: </strong>In the study, the superficial expression of CTLA-4 receptor on T lymphocytes was enhanced in children with diabetes lasting <5 years (p<0.005) and over 5 years without vascular complications (p<0.01) versus healthy patients and tend to normalize in the presence of developing vascular complications In contrast, the expression of costimulatory molecule CD28 was decreased in children with type 1 diabetes lasting <5 years (p<0.05) as well as in children with developing vascular complications (p<0.01) versus the control group.</p>","PeriodicalId":11550,"journal":{"name":"Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24780179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renata Wasikowa, Anna Noczyńska, Aleksander Basiak
Diabetes type 1 is, as we know, a chronic progressive disease, which requires a substitutional therapy with insulin for the whole life. The cause is a definite destruction of the pancreatic beta cells. For many years there have been intensive investigations on the possibility to obtain a complete, persistent withdrawal of the symptoms. Substitution of the destroyed, not active cells, could take place after transplantation of the whole pancreas, transplantation of pancreatic islets or transplantation of stem cells. This is now the only method which may cause an independence from exogenous insulin, persistent normoglycemia, normal HbA1c level, without risk of hypoglycemia. Pancreas and islets transplantations, however, are connected till now with the necessity of an immunosuppressive therapy for the whole life, with the toxicity of the drugs, incidence of frequent infections and malignancy. Pancreas transplantation is a serious surgical intervention, connected with numerous risks and complications, considerably less risk appears in islet cell transplantations. Since 2000 exclusively islet cell transplantations have been performed. One of the leading centers is Edmonton, where professor Shapiro prepared the so called. Edmonton protocol which is characterized by using corticosteroid-free immunosuppressive drugs, islet cells from two or more donors, repeated till the attainment of insulin dependence. A problem now is that the islets are obtained from cadavers. Therefore intensive research is conducted for alternative sources of beta cells. At this moment it is mostly preferred for receiving a sufficient number of insulin producing cells to develop stem cells with a subsequent differentiation to insulin producing cells. The mentioned cells have an unlimited ability of reproduction, in this case also immunosuppressive therapy is not necessary. Alternative sources of beta cells are cells achieved on the genetic engineering, embryonic or adult somatic stem cells. It is however important to stress, that adult stem cells as insulin producing cells are not unequivocally identified. For obtaining better, permanent results after transplantation the following are important: optimalization of "islands growth" in the liver, prevention of the early inflammations, further development of highly selective, well tolerated, corticosteroid-free immunosuppressive drugs, identification of rejecting markers, induction of immunotolerance, micro- and macro-capsulation of the islets to protect the recipient against the immunological attack. Several multicenter studies in important scientific centers are opened, there is also Juvenile Research Foundation International. In spite of a permanent progress there are still many important problems to solve. It is necessary to institute further multicenter, international research to ascertain the effect of transplantation concerning the normalisation of glycemia, prevention or inhibition of the progress of diabetic complications
{"title":"[Transplantation in diabetes type 1--current problems and perspectives].","authors":"Renata Wasikowa, Anna Noczyńska, Aleksander Basiak","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diabetes type 1 is, as we know, a chronic progressive disease, which requires a substitutional therapy with insulin for the whole life. The cause is a definite destruction of the pancreatic beta cells. For many years there have been intensive investigations on the possibility to obtain a complete, persistent withdrawal of the symptoms. Substitution of the destroyed, not active cells, could take place after transplantation of the whole pancreas, transplantation of pancreatic islets or transplantation of stem cells. This is now the only method which may cause an independence from exogenous insulin, persistent normoglycemia, normal HbA1c level, without risk of hypoglycemia. Pancreas and islets transplantations, however, are connected till now with the necessity of an immunosuppressive therapy for the whole life, with the toxicity of the drugs, incidence of frequent infections and malignancy. Pancreas transplantation is a serious surgical intervention, connected with numerous risks and complications, considerably less risk appears in islet cell transplantations. Since 2000 exclusively islet cell transplantations have been performed. One of the leading centers is Edmonton, where professor Shapiro prepared the so called. Edmonton protocol which is characterized by using corticosteroid-free immunosuppressive drugs, islet cells from two or more donors, repeated till the attainment of insulin dependence. A problem now is that the islets are obtained from cadavers. Therefore intensive research is conducted for alternative sources of beta cells. At this moment it is mostly preferred for receiving a sufficient number of insulin producing cells to develop stem cells with a subsequent differentiation to insulin producing cells. The mentioned cells have an unlimited ability of reproduction, in this case also immunosuppressive therapy is not necessary. Alternative sources of beta cells are cells achieved on the genetic engineering, embryonic or adult somatic stem cells. It is however important to stress, that adult stem cells as insulin producing cells are not unequivocally identified. For obtaining better, permanent results after transplantation the following are important: optimalization of \"islands growth\" in the liver, prevention of the early inflammations, further development of highly selective, well tolerated, corticosteroid-free immunosuppressive drugs, identification of rejecting markers, induction of immunotolerance, micro- and macro-capsulation of the islets to protect the recipient against the immunological attack. Several multicenter studies in important scientific centers are opened, there is also Juvenile Research Foundation International. In spite of a permanent progress there are still many important problems to solve. It is necessary to institute further multicenter, international research to ascertain the effect of transplantation concerning the normalisation of glycemia, prevention or inhibition of the progress of diabetic complications","PeriodicalId":11550,"journal":{"name":"Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24780184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jadwiga Peczyńska, Mirosława Urban, Barbara Głowińska, Bozena Florys
Unlabelled: The inability of the patient to recognize the risk of hypoglycemia is a very frequent phenomenon, but it is also often an underestimated complication in diabetes treated with insulin. The results of DCCT trial revealed that intensification in insulin therapy increases three-fold the risk of severe hypoglycaemia. Feeling the state of hypoglycaemia is the basic defensive mechanism in patients with diabetes type 1, making possible to start the self treatment. The decreased consciousness of hypoglycaemia makes limitations to intensive insulin therapy, which main aim is to stop later complications. THE AIM OF THE STUDY was to answer the questions: 1. How often does lack of consciousness of hypoglycaemia occur in children and adolescents with diabetes type 1. 2. What are the possible factors influencing appearance of hypoglycaemia. 3. Is lack of hypoglycaemia consciousness of a risk factor for severe hypoglycaemia.
Material and methods: The study was carried out on 318 patients aged x=13.6 yrs (4-21), suffering from diabetes, mean 6.6 yrs (2-18). The study was retrospective taking into consideration the period from 1.01.1998 to 31.12.2002.
Results: In the analysis of the questionnaire assessing the occurrence of hypoglycaemia it was found that 82 patients (25.8%) have problems with feeling the state of hypoglycaemia. We analyzed the influence of time of lasting diabetes and we found that patients with a longer duration of the disease more frequently have problems with feeling hypoglycaemia, 57% patients with lack of hypoglycaemia consciousness have bad metabolic control of the disease. In the analyzed period, 64 incidences of severe hypoglycaemia in 48 patients (30 boys and 18 girls) were found. In patients with lack of consciousness of feeling hypoglycaemia the incidences of severe hypoglycaemia occurred ten times more frequently compared to patients who feel hypoglycaemia. Sleeping makes it impossible to perceive early symptoms of hypoglycaemia: in our patients 51 severe incidences (79.7%) occurred at 1.00-3.00 a.m., 6 (9.3%) occurred at daybreak and 7 (11%) in the evening.
Conclusions: 1. In patients with diabetes type 1 the lack of hypoglycaemia consciousness occurs in about 25%. 2. The lack of hypoglycaemia consciousness is closely connected with time of diabetes duration and with recurrence of hypoglycaemia incidences. 3. Patients with lack of hypoglycaemia consciousness are at greater risk for severe hypoglycemia.
{"title":"[How often does decreased consciousness of hypoglycaemia occur in children and adolescents with diabetes type 1 and what are its consequences?].","authors":"Jadwiga Peczyńska, Mirosława Urban, Barbara Głowińska, Bozena Florys","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Unlabelled: </strong>The inability of the patient to recognize the risk of hypoglycemia is a very frequent phenomenon, but it is also often an underestimated complication in diabetes treated with insulin. The results of DCCT trial revealed that intensification in insulin therapy increases three-fold the risk of severe hypoglycaemia. Feeling the state of hypoglycaemia is the basic defensive mechanism in patients with diabetes type 1, making possible to start the self treatment. The decreased consciousness of hypoglycaemia makes limitations to intensive insulin therapy, which main aim is to stop later complications. THE AIM OF THE STUDY was to answer the questions: 1. How often does lack of consciousness of hypoglycaemia occur in children and adolescents with diabetes type 1. 2. What are the possible factors influencing appearance of hypoglycaemia. 3. Is lack of hypoglycaemia consciousness of a risk factor for severe hypoglycaemia.</p><p><strong>Material and methods: </strong>The study was carried out on 318 patients aged x=13.6 yrs (4-21), suffering from diabetes, mean 6.6 yrs (2-18). The study was retrospective taking into consideration the period from 1.01.1998 to 31.12.2002.</p><p><strong>Results: </strong>In the analysis of the questionnaire assessing the occurrence of hypoglycaemia it was found that 82 patients (25.8%) have problems with feeling the state of hypoglycaemia. We analyzed the influence of time of lasting diabetes and we found that patients with a longer duration of the disease more frequently have problems with feeling hypoglycaemia, 57% patients with lack of hypoglycaemia consciousness have bad metabolic control of the disease. In the analyzed period, 64 incidences of severe hypoglycaemia in 48 patients (30 boys and 18 girls) were found. In patients with lack of consciousness of feeling hypoglycaemia the incidences of severe hypoglycaemia occurred ten times more frequently compared to patients who feel hypoglycaemia. Sleeping makes it impossible to perceive early symptoms of hypoglycaemia: in our patients 51 severe incidences (79.7%) occurred at 1.00-3.00 a.m., 6 (9.3%) occurred at daybreak and 7 (11%) in the evening.</p><p><strong>Conclusions: </strong>1. In patients with diabetes type 1 the lack of hypoglycaemia consciousness occurs in about 25%. 2. The lack of hypoglycaemia consciousness is closely connected with time of diabetes duration and with recurrence of hypoglycaemia incidences. 3. Patients with lack of hypoglycaemia consciousness are at greater risk for severe hypoglycemia.</p>","PeriodicalId":11550,"journal":{"name":"Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24671727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maryna Krawczuk-Rybak, Anna Kitszel, Sławomir Wołczyński
Unlabelled: We determined serum levels of insulin-like growth factors (IGF-1, IGF-2) and binding proteins (IGFBP-2 and IGFBP-3) at diagnosis (I), during (II) and after therapy (III) in 28 children treated for ALL.
Results: 1) Serum absolute levels of IGF-1, IGF-2, IGFBP-3 rose and IGFBP-2 - decreased during analysis. 2) Mean values of IGF-1 SDS were similar at diagnosis, during and after treatment (-1.78+/-0.9 vs. -1.86+/-1.36 vs. -1.8+/-0.83). IGF-2 SDS rose from 0.06+/-1.45 (I) to 0.64+/-1.4 (II) and to 0.83+/- 2.01 (III) and IGFBP-3 SDS increased from -0.23+/-2.23 (I) to 0.92+/-1.95 (II) and to 1.76+/-2.43 (III). IGFBP-2 SDS were elevated at diagnosis, during and after treatment 11.94+/-9.42 (I) and 10.58+/-7.37 (II) and to 7.90+/-7.20 (III). 3) We observed positive correlations between: a) IGF-1 and IGFBP-3 at diagnosis (r=0.58 p=0.0001), during (r=0.69 p=0.0001) and after treatment (r=0.79 p=0.00001), b) IGF-1 and IGF-2 at diagnosis (r=0.57 p=0.00001) and after the end of therapy (r=0.48 p=0.01) c) IGF-2 and IGFBP-3 at diagnosis (r=0.7 p=0.0004) and after treatment (r=0.64 p=0.003) and d) negative correlation between IGF-1 and IGFBP-2 - at diagnosis (r=0.38 p=0.02) and after treatment (r=0.43 p=0.02).
Conclusions: Decreased serum IGF-1 and elevated IGFBP-2 were observed at diagnosis and during treatment for ALL suggesting that especially IGFBP-2 may be related to the proliferation of lymphoblasts.
{"title":"[Changes in concentrations of circulating insulin-like growth factors I and II and binding proteins BP-2 and BP-3 in children treated for acute lymphoblastic leukaemia].","authors":"Maryna Krawczuk-Rybak, Anna Kitszel, Sławomir Wołczyński","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Unlabelled: </strong>We determined serum levels of insulin-like growth factors (IGF-1, IGF-2) and binding proteins (IGFBP-2 and IGFBP-3) at diagnosis (I), during (II) and after therapy (III) in 28 children treated for ALL.</p><p><strong>Results: </strong>1) Serum absolute levels of IGF-1, IGF-2, IGFBP-3 rose and IGFBP-2 - decreased during analysis. 2) Mean values of IGF-1 SDS were similar at diagnosis, during and after treatment (-1.78+/-0.9 vs. -1.86+/-1.36 vs. -1.8+/-0.83). IGF-2 SDS rose from 0.06+/-1.45 (I) to 0.64+/-1.4 (II) and to 0.83+/- 2.01 (III) and IGFBP-3 SDS increased from -0.23+/-2.23 (I) to 0.92+/-1.95 (II) and to 1.76+/-2.43 (III). IGFBP-2 SDS were elevated at diagnosis, during and after treatment 11.94+/-9.42 (I) and 10.58+/-7.37 (II) and to 7.90+/-7.20 (III). 3) We observed positive correlations between: a) IGF-1 and IGFBP-3 at diagnosis (r=0.58 p=0.0001), during (r=0.69 p=0.0001) and after treatment (r=0.79 p=0.00001), b) IGF-1 and IGF-2 at diagnosis (r=0.57 p=0.00001) and after the end of therapy (r=0.48 p=0.01) c) IGF-2 and IGFBP-3 at diagnosis (r=0.7 p=0.0004) and after treatment (r=0.64 p=0.003) and d) negative correlation between IGF-1 and IGFBP-2 - at diagnosis (r=0.38 p=0.02) and after treatment (r=0.43 p=0.02).</p><p><strong>Conclusions: </strong>Decreased serum IGF-1 and elevated IGFBP-2 were observed at diagnosis and during treatment for ALL suggesting that especially IGFBP-2 may be related to the proliferation of lymphoblasts.</p>","PeriodicalId":11550,"journal":{"name":"Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24671728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jadwiga Peczyńska, Mirosława Urban, Beata Urban, Barbara Głowińska, Bozena Florys
Objective: The purpose of the study was the evaluation of growth hormone (GH), insulin-like growth factor (IGF-1), insulin-like growth factor binding protein (IGFBP-3) and vascular endothelial growth factor (VEGF) in adolescents with type 1 diabetes as well as the relationship between the concentration of examined proteins and the early development of diabetic microangiopathy.
Research design and methods: The study included 68 patients aged 15.54+/-2.9 years with type 1 diabetes. They were divided into groups: I - adolescents with the beginning of vascular complications, II - without complications. Controls consisted of healthy adolescents. GH, IGF-1, IGFBP-3 and VEGF were determined with use of ready kits.
Results: The increased levels of GH were found in diabetic adolescents in comparison with controls (10.11+/-16.21 vs. 2.89+/-4.03 micro IU/ml, p<0.05). The levels of IGF 1 were lower in adolescents with type 1 diabetes than in controls (283.48+/-117.36 vs. 427.95+/-177.48 ng/ml, p<0.05), as well as the levels of IGFBP-3 (5555.21+/-1158 vs. 6622.18+/-1110 pg/ml, p<0.05). Significantly higher concentration of VEGF was revealed in diabetic adolescents in comparison with controls (328.68+/-251 vs. 132.19+/-85 pg/ml, p<0.05). The highest levels of VEGF were reported in diabetic patients with retinopathy in comparison with patients without complications.
Conclusions: The impaired activity of GH-IGF-1-IGFBP-3 axis may be responsible for the development of diabetic microangiopathy. The evaluation of VEGF concentration can be a sensitive early marker of microangiopathy.
目的:评价青少年1型糖尿病患者生长激素(GH)、胰岛素样生长因子(IGF-1)、胰岛素样生长因子结合蛋白(IGFBP-3)和血管内皮生长因子(VEGF)水平及其与糖尿病微血管病变早期发展的关系。研究设计与方法:68例1型糖尿病患者,年龄15.54±2.9岁。他们被分为两组:I -开始出现血管并发症的青少年,II -无并发症。对照组由健康的青少年组成。使用ready试剂盒检测GH、IGF-1、IGFBP-3和VEGF。结果:糖尿病青少年GH水平明显高于对照组(10.11+/-16.21 vs. 2.89+/-4.03微IU/ml)。结论:GH- igf -1- igfbp -3轴活性受损可能与糖尿病微血管病变的发生有关。VEGF浓度的评估可作为微血管病变的早期敏感指标。
{"title":"[Assessment of growth factor levels in adolescents with type 1 diabetes mellitus and the beginning of diabetic microangiopathy].","authors":"Jadwiga Peczyńska, Mirosława Urban, Beata Urban, Barbara Głowińska, Bozena Florys","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>The purpose of the study was the evaluation of growth hormone (GH), insulin-like growth factor (IGF-1), insulin-like growth factor binding protein (IGFBP-3) and vascular endothelial growth factor (VEGF) in adolescents with type 1 diabetes as well as the relationship between the concentration of examined proteins and the early development of diabetic microangiopathy.</p><p><strong>Research design and methods: </strong>The study included 68 patients aged 15.54+/-2.9 years with type 1 diabetes. They were divided into groups: I - adolescents with the beginning of vascular complications, II - without complications. Controls consisted of healthy adolescents. GH, IGF-1, IGFBP-3 and VEGF were determined with use of ready kits.</p><p><strong>Results: </strong>The increased levels of GH were found in diabetic adolescents in comparison with controls (10.11+/-16.21 vs. 2.89+/-4.03 micro IU/ml, p<0.05). The levels of IGF 1 were lower in adolescents with type 1 diabetes than in controls (283.48+/-117.36 vs. 427.95+/-177.48 ng/ml, p<0.05), as well as the levels of IGFBP-3 (5555.21+/-1158 vs. 6622.18+/-1110 pg/ml, p<0.05). Significantly higher concentration of VEGF was revealed in diabetic adolescents in comparison with controls (328.68+/-251 vs. 132.19+/-85 pg/ml, p<0.05). The highest levels of VEGF were reported in diabetic patients with retinopathy in comparison with patients without complications.</p><p><strong>Conclusions: </strong>The impaired activity of GH-IGF-1-IGFBP-3 axis may be responsible for the development of diabetic microangiopathy. The evaluation of VEGF concentration can be a sensitive early marker of microangiopathy.</p>","PeriodicalId":11550,"journal":{"name":"Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24672828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jolanta Wierzba, Maria Korpal-Szczyrska, Anna Balcerska, Halina Kamińska
We report a case of diabetic ketoacidosis complicated by acute myocarditis which was confirmed by necroscopy. A 14 year boy was hospitalised with severe ketoacidosis. The patient levels of creatinine, transaminases were elevated, symptoms of hearth disease were complicated by dehydration and high temperature. An episode of upper respiratory viral infection before the onset of acute diabetes suggested that the patient died from viral myocarditis.
{"title":"[Sudden death caused by myocarditis in a 14-year old boy with type I diabetes].","authors":"Jolanta Wierzba, Maria Korpal-Szczyrska, Anna Balcerska, Halina Kamińska","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We report a case of diabetic ketoacidosis complicated by acute myocarditis which was confirmed by necroscopy. A 14 year boy was hospitalised with severe ketoacidosis. The patient levels of creatinine, transaminases were elevated, symptoms of hearth disease were complicated by dehydration and high temperature. An episode of upper respiratory viral infection before the onset of acute diabetes suggested that the patient died from viral myocarditis.</p>","PeriodicalId":11550,"journal":{"name":"Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24672829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jolanta Szczepańska Kostro, Joanna Tołwińska, Mirosława Urban, Barbara Głowińska
Unlabelled: A total of 25 patients (10 girls and 15 boys) aged 8.1-16.9 years (mean 13.3+/-1.8 years), height 1.15-1.61 m (mean 1.4+/-0.1 m), body area 0.84-1.47 m2 (mean 1.14+/-0.18 m2) were examined in our study. After 12-month--rhGH therapy, 23 children (9 girls and 14 boys) were re-evaluated. Twenty two healthy and slim children (11 girls and 11 boys) aged 6.6-16 years (mean 12,6+/-2.7 years), height 1.33-1.8 m (mean 1.58+/-0.16), body area 0.93-1.8 m2 (mean 1.38+/-0.3 m2) with a family history without atherosclerosis and cardiovascular diseases constituted controls. Mass and function of LV were evaluated by means of M-mode and 2D echocardiography and the Doppler method with simultaneous 2D picture recording. Systolic function parameters (SF and EF) were normal in each patient before therapy. LV systolic fraction (SF) equaled on average 35.4+/-4.5 % in the examined group and 36.7+/-3.9 % in controls. LV ejection fraction (EF) was on average 65.1+/-5.9 % in the examined group and 67.9+/-6.4 % in controls. The differences noted were not statistically significant. After a year-rhGH therapy, SF and EF were within a normal range in each patient. SF was on average 35.9+/-3.6% in the examined group and 36.7+/-3.9% in controls. EF was on average 65.7+/-4.6% in the examined group and 67.9+/-6.4% in controls. The differences were not statistically significant. SF and EF did not differ before and after rhGH therapy. LV mass indexed by body superficial area (LVA/BSA) equaled 68.3+/-18.6 g/m2 before therapy and did not differ significantly in comparison with controls (68.2+/-15.5 g/m2). After a year-GH therapy, LV/BSA was significantly higher when compared to LV/BSA mass before therapy (78.2+/-14.9 g/m2 vs 68.3+/-18 6 g/m2, p<0.05). After a year-GH therapy LV/BSA mass was significantly higher in comparison with LV/BSA mass before therapy (78.2+/-14.9 g/m2 vs 68.3+/-18.6 g/m2, p< 0.05). Before therapy, IVRT parameter was found significantly extended in comparison with controls (70.8+/-14.2 vs 64.1+/-8.5 ms, p<0.05). Other parameters characterising LV diastolic function were not significantly different between the groups. After a year-GH therapy, IVRT parameter was still extended in comparison with controls (72.3+/-9.2 vs 64.1+/-8.5 ms, p<0.05). No significant differences were observed with regard to IVRT before and after therapy.
Conclusion: 1. A significant extension of isovolumetric relaxation time (IVRT) was proved in children with GH deficiency, which may suggest an impaired diastolic function of the heart left ventricle. 2. 12-month-rhGH replacement therapy causes an increase in the left ventricle mass when compared to the values before therapy, whereas isovolumetric relaxation time remains still longer. 3. Children with GH deficiency should have their circulatory system monitored to observe the dynamics of the left ventricle functional disorders.
{"title":"[Left ventricular mass and function in growth hormone deficient children and adolescents before and after one year of recombinant human growth hormone (GH) replacement therapy].","authors":"Jolanta Szczepańska Kostro, Joanna Tołwińska, Mirosława Urban, Barbara Głowińska","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Unlabelled: </strong>A total of 25 patients (10 girls and 15 boys) aged 8.1-16.9 years (mean 13.3+/-1.8 years), height 1.15-1.61 m (mean 1.4+/-0.1 m), body area 0.84-1.47 m2 (mean 1.14+/-0.18 m2) were examined in our study. After 12-month--rhGH therapy, 23 children (9 girls and 14 boys) were re-evaluated. Twenty two healthy and slim children (11 girls and 11 boys) aged 6.6-16 years (mean 12,6+/-2.7 years), height 1.33-1.8 m (mean 1.58+/-0.16), body area 0.93-1.8 m2 (mean 1.38+/-0.3 m2) with a family history without atherosclerosis and cardiovascular diseases constituted controls. Mass and function of LV were evaluated by means of M-mode and 2D echocardiography and the Doppler method with simultaneous 2D picture recording. Systolic function parameters (SF and EF) were normal in each patient before therapy. LV systolic fraction (SF) equaled on average 35.4+/-4.5 % in the examined group and 36.7+/-3.9 % in controls. LV ejection fraction (EF) was on average 65.1+/-5.9 % in the examined group and 67.9+/-6.4 % in controls. The differences noted were not statistically significant. After a year-rhGH therapy, SF and EF were within a normal range in each patient. SF was on average 35.9+/-3.6% in the examined group and 36.7+/-3.9% in controls. EF was on average 65.7+/-4.6% in the examined group and 67.9+/-6.4% in controls. The differences were not statistically significant. SF and EF did not differ before and after rhGH therapy. LV mass indexed by body superficial area (LVA/BSA) equaled 68.3+/-18.6 g/m2 before therapy and did not differ significantly in comparison with controls (68.2+/-15.5 g/m2). After a year-GH therapy, LV/BSA was significantly higher when compared to LV/BSA mass before therapy (78.2+/-14.9 g/m2 vs 68.3+/-18 6 g/m2, p<0.05). After a year-GH therapy LV/BSA mass was significantly higher in comparison with LV/BSA mass before therapy (78.2+/-14.9 g/m2 vs 68.3+/-18.6 g/m2, p< 0.05). Before therapy, IVRT parameter was found significantly extended in comparison with controls (70.8+/-14.2 vs 64.1+/-8.5 ms, p<0.05). Other parameters characterising LV diastolic function were not significantly different between the groups. After a year-GH therapy, IVRT parameter was still extended in comparison with controls (72.3+/-9.2 vs 64.1+/-8.5 ms, p<0.05). No significant differences were observed with regard to IVRT before and after therapy.</p><p><strong>Conclusion: </strong>1. A significant extension of isovolumetric relaxation time (IVRT) was proved in children with GH deficiency, which may suggest an impaired diastolic function of the heart left ventricle. 2. 12-month-rhGH replacement therapy causes an increase in the left ventricle mass when compared to the values before therapy, whereas isovolumetric relaxation time remains still longer. 3. Children with GH deficiency should have their circulatory system monitored to observe the dynamics of the left ventricle functional disorders.</p>","PeriodicalId":11550,"journal":{"name":"Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24780178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Noczyńska, Teresa Zak, Renata Wasikowa, Marcin Kałuzny
The authors present the course of puberty in three girls after surgery because of hormonally active ovarian tumours diagnosed and operated at the age of 3, 6 and 9 years, respectively. In the youngest patient with folliculoma ovari chemotherapy was also given, and girl No. 3 with luteinic capsule was treated for one year with decapeptyl because idiopathic precocious puberty was diagnosed. At present all three girls are in good physical condition with age-adequate development and puberty.
{"title":"[Personal observations of puberty in girls after unilateral ovariectomy].","authors":"Anna Noczyńska, Teresa Zak, Renata Wasikowa, Marcin Kałuzny","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The authors present the course of puberty in three girls after surgery because of hormonally active ovarian tumours diagnosed and operated at the age of 3, 6 and 9 years, respectively. In the youngest patient with folliculoma ovari chemotherapy was also given, and girl No. 3 with luteinic capsule was treated for one year with decapeptyl because idiopathic precocious puberty was diagnosed. At present all three girls are in good physical condition with age-adequate development and puberty.</p>","PeriodicalId":11550,"journal":{"name":"Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24780185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joanna Tołwińska, Barbara Głowińska, Mirosława Urban
Introduction: According to very well documented onset of atherosclerosis in early childhood, scientists are looking for good diagnostic methods for evaluating first changes in arterial blood vessels noninvasively. We want to know more about the pathogenetic mechanisms and about changes in vessels especially in group of young people with risk factors of premature atherosclerosis. The significance of endothelial dysfunction in very early phase of this process is known very well so far. High resolution echocardiography seems to be a good method which allows to examine arteries in children and adolescents. Because of localization, brachial and carotid arteries are very good field for this kind of examinations. THE AIM of this study was the evaluation with high resolution echocardiography of endothelial function in type 1 diabetes children and adolescents. We also measured the intimal plus medial thickness in carotid communis arteries (IMT).
Material and methods: We examined a group of 64 children (29 boys and 35 girls) aged 14.8-16.2 yr (mean 15.5 yr) suffering from diabetes type 1. The control group consisted of 24 children (9 boys, 15 girls) in similar age. Using high resolution echocardiography, B-mode images, we measured in the diastole phase, distance "m-m" in brachial arteries (distance between two "m" lines which are borders among media and adventitia of near and far wall of the artery) at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation FMD), again at rest and after sublingual glyceryl trinitrate (causing endothelium-independent dilatation NTGMD). Using Doppler technic we evaluated baseline flow and calculated the degree of reactive hyperemia. We also measured intimal plus medial thickness in every carotid artery three times and calculated mean value. In our analysis we estimated the concentrations of cholesterol, HDL- cholesterol, LDL-cholesterol and triglycerides.
Results: We noticed higher IMT values in the whole examined group compared to the control group (0.52 mm vs. 0.43 mm, p<0.05). In diabetic children the vessel size was similar to control group but FMD was significantly impaired (5.56% vs. 9.47%, p<0.05). The level of triglycerides and total cholesterol was higher in the examined group.
Conclusions: 1. The evaluation of IMT in the carotid arteries in patients with type 1 diabetes showed a more advanced degree of atherosclerotic changes in this group compared to healthy controls. 2. FMD evaluated in brachial artery is a usefull tool in assessing impaired endothelial function in people suffering from the risks factors of atherosclerosis. 3. Ultrasonographic methods of evaluating atherosclerotic changes in arterial vessels should be more often used in practice as relatively easy, noninvasive and inexpensive.
导读:根据对儿童早期动脉粥样硬化发病的详细记录,科学家们正在寻找良好的诊断方法,以无创地评估动脉血管的首次变化。我们想要了解更多的发病机制和血管的变化,特别是在有过早动脉粥样硬化危险因素的年轻人群体中。到目前为止,内皮功能障碍在这一过程的早期阶段的重要性是众所周知的。高分辨率超声心动图似乎是一个很好的方法,允许检查动脉在儿童和青少年。由于定位,臂动脉和颈动脉是很好的检查领域。本研究的目的是用高分辨率超声心动图评价1型糖尿病儿童和青少年的内皮功能。我们还测量了颈动脉社区动脉(IMT)的内膜和内侧厚度。材料和方法:我们检查了64名儿童(29名男孩和35名女孩),年龄14.8-16.2岁(平均15.5岁),患有1型糖尿病。对照组为24例同龄儿童(男童9例,女童15例)。使用高分辨率超声心动图,b型图像,我们测量了舒张期肱动脉的距离“m-m”(两条“m”线之间的距离,即动脉近壁和远壁的中膜和外膜之间的边界),静止时,反应性充血期间(流量增加导致内皮依赖性扩张FMD),再次静止时和舌下三硝酸甘油(导致内皮依赖性扩张NTGMD)。采用多普勒技术评估基线血流并计算反应性充血的程度。我们还测量了每条颈动脉的内膜和内侧厚度三次,并计算了平均值。在我们的分析中,我们估计了胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯的浓度。结果:我们注意到,与对照组相比,整个检查组的IMT值更高(0.52 mm vs. 0.43 mm)。对1型糖尿病患者颈动脉IMT的评估显示,与健康对照组相比,该组患者的动脉粥样硬化改变程度更高。2. 肱动脉FMD评估是评估动脉粥样硬化危险因素患者内皮功能受损的有用工具。3.超声检查动脉粥样硬化改变的方法相对简单、无创且价格低廉,因此应在实践中得到更多的应用。
{"title":"[Ultrasonographic evaluation of atherosclerotic changes in carotid and brachial arteries in children with type 1 diabetes].","authors":"Joanna Tołwińska, Barbara Głowińska, Mirosława Urban","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>According to very well documented onset of atherosclerosis in early childhood, scientists are looking for good diagnostic methods for evaluating first changes in arterial blood vessels noninvasively. We want to know more about the pathogenetic mechanisms and about changes in vessels especially in group of young people with risk factors of premature atherosclerosis. The significance of endothelial dysfunction in very early phase of this process is known very well so far. High resolution echocardiography seems to be a good method which allows to examine arteries in children and adolescents. Because of localization, brachial and carotid arteries are very good field for this kind of examinations. THE AIM of this study was the evaluation with high resolution echocardiography of endothelial function in type 1 diabetes children and adolescents. We also measured the intimal plus medial thickness in carotid communis arteries (IMT).</p><p><strong>Material and methods: </strong>We examined a group of 64 children (29 boys and 35 girls) aged 14.8-16.2 yr (mean 15.5 yr) suffering from diabetes type 1. The control group consisted of 24 children (9 boys, 15 girls) in similar age. Using high resolution echocardiography, B-mode images, we measured in the diastole phase, distance \"m-m\" in brachial arteries (distance between two \"m\" lines which are borders among media and adventitia of near and far wall of the artery) at rest, during reactive hyperaemia (with increased flow causing endothelium-dependent dilatation FMD), again at rest and after sublingual glyceryl trinitrate (causing endothelium-independent dilatation NTGMD). Using Doppler technic we evaluated baseline flow and calculated the degree of reactive hyperemia. We also measured intimal plus medial thickness in every carotid artery three times and calculated mean value. In our analysis we estimated the concentrations of cholesterol, HDL- cholesterol, LDL-cholesterol and triglycerides.</p><p><strong>Results: </strong>We noticed higher IMT values in the whole examined group compared to the control group (0.52 mm vs. 0.43 mm, p<0.05). In diabetic children the vessel size was similar to control group but FMD was significantly impaired (5.56% vs. 9.47%, p<0.05). The level of triglycerides and total cholesterol was higher in the examined group.</p><p><strong>Conclusions: </strong>1. The evaluation of IMT in the carotid arteries in patients with type 1 diabetes showed a more advanced degree of atherosclerotic changes in this group compared to healthy controls. 2. FMD evaluated in brachial artery is a usefull tool in assessing impaired endothelial function in people suffering from the risks factors of atherosclerosis. 3. Ultrasonographic methods of evaluating atherosclerotic changes in arterial vessels should be more often used in practice as relatively easy, noninvasive and inexpensive.</p>","PeriodicalId":11550,"journal":{"name":"Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24671729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bozena Florys, Agnieszka Ołdytowska, Barbara Głowińska, Jadwiga Peczyńska, Mirosława Urban
Unlabelled: The critical study showing advantages of intensive insulin therapy in comparison with the classic method was Diabetes Control and Complications Trial. Conclusion of that study was unequivocal: hyperglycemia has a significant influence on the development of the chronic diabetes complications. THE AIM of this study was to estimate the influence of the conventional insulin therapy in the past and its duration on the development of complications in patients suffering from type 1 diabetes for more than 5 years.
Material and methods: 185 patients aged 16.7 years (+/-3.4) with diabetes onset in the age 8.4 years (+/-3.8) participated in this study. There were 84 girls and 101 boys. More of them were treated by classic insulin therapy at the beginning of disease (n=148). 37 persons had intensive insulin therapy all the time.
Results: The presence of at least one complication was found in 49 persons (26.5%), two complications - in 14 patients (7.57%) and three complications in 4 patients (2.16%). The conventional therapy duration was twice longer in patients with retinopathy. The significant influence of the age, the age of diabetes onset and duration was found in those patients. Comparing the groups of patients treated conventionally less than 3.5 years and more than 3.5 years it was found that patients in the first group were older, fell ill later and they had longer diabetes duration than patients in the second group. The risk of retinopathy increases from 4.2% to 8.9% in patients treated conventionally more than 3.5 years. The risk of diabetic cataract is 5 times higher in that group.
Conclusions: Chronic complications of diabetes occur in 26.5 % patients with a diabetes duration of at least 5 years. CIT is the risk factor of the eye complications in diabetes, particularly when applied longer than 3.5 years. The prolongation of CIT over 3.5 years increases the risk of retinopathy twice and the risk of cataract 5 times in patients with type 1 diabetes. So the early intensification of insulin therapy reduces the risk of the retinopathy and cataract development in later course of the disease.
{"title":"[Prevalence of chronic diabetes complications depending on the method of insulin therapy in children and adolescents with type 1 diabetes].","authors":"Bozena Florys, Agnieszka Ołdytowska, Barbara Głowińska, Jadwiga Peczyńska, Mirosława Urban","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Unlabelled: </strong>The critical study showing advantages of intensive insulin therapy in comparison with the classic method was Diabetes Control and Complications Trial. Conclusion of that study was unequivocal: hyperglycemia has a significant influence on the development of the chronic diabetes complications. THE AIM of this study was to estimate the influence of the conventional insulin therapy in the past and its duration on the development of complications in patients suffering from type 1 diabetes for more than 5 years.</p><p><strong>Material and methods: </strong>185 patients aged 16.7 years (+/-3.4) with diabetes onset in the age 8.4 years (+/-3.8) participated in this study. There were 84 girls and 101 boys. More of them were treated by classic insulin therapy at the beginning of disease (n=148). 37 persons had intensive insulin therapy all the time.</p><p><strong>Results: </strong>The presence of at least one complication was found in 49 persons (26.5%), two complications - in 14 patients (7.57%) and three complications in 4 patients (2.16%). The conventional therapy duration was twice longer in patients with retinopathy. The significant influence of the age, the age of diabetes onset and duration was found in those patients. Comparing the groups of patients treated conventionally less than 3.5 years and more than 3.5 years it was found that patients in the first group were older, fell ill later and they had longer diabetes duration than patients in the second group. The risk of retinopathy increases from 4.2% to 8.9% in patients treated conventionally more than 3.5 years. The risk of diabetic cataract is 5 times higher in that group.</p><p><strong>Conclusions: </strong>Chronic complications of diabetes occur in 26.5 % patients with a diabetes duration of at least 5 years. CIT is the risk factor of the eye complications in diabetes, particularly when applied longer than 3.5 years. The prolongation of CIT over 3.5 years increases the risk of retinopathy twice and the risk of cataract 5 times in patients with type 1 diabetes. So the early intensification of insulin therapy reduces the risk of the retinopathy and cataract development in later course of the disease.</p>","PeriodicalId":11550,"journal":{"name":"Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24671730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}