Clinical relevance of estimating circulating interleukin-17 and interleukin-23 during methylprednisolone therapy in Graves' orbitopathy: A preliminary study.

PURPOSE: Graves' orbitopathy (GO) is an important problem in endocrinology. Currently used methods of assessing the degree of activity of the autoimmune process are not satisfactory. Therefore, there is a need to establish indicators of greater utility. PATIENTS AND METHODS: The study included 35 patients: 15 with GO, 10 with Graves' disease (GD) without GO and 10 controls. Patients with GO received methylprednisolone (MP) for 12 weeks. Concentrations of thyrotropin receptor antibodies (TSHRab), interleukin 17 (IL-17) and 23 (IL-23) were obtained before administering the first dose of MP, after 6 and 12 weeks of therapy, and 3 months after treatment cessation. Patients were classified as responders (n â€‹= â€‹11) if a reduction of ≥2 points in the Clinical Activity Score (CAS) was observed. RESULTS: A significant decrease in exophthalmos, muscles' thickness and CAS value was demonstrated after MP treatment in responders group. Significantly higher concentrations were found in baseline IL-23 between the GD and GO groups compared to controls. No statistically significant differences in serum concentrations of IL-17 and IL-23 were observed during treatment with MP and 3 months after treatment cessation. A statistically significant reduction in TSHRab concentration was demonstrated 3 months after treatment cessation compared to baseline values in responders group. CONCLUSIONS: Low baseline IL-17 concentration, in addition to high TSHRab titre, serves as marker of disease activity. Although, we expect that low IL-23 concentration, in addition to high TSHRab titre, could be used as predictors of disease activity and a prognostic factor of response to immunosuppressive therapy in GO.

Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves' orbitopathy.

INTRODUCTION: Graves' orbitopathy (GO) is a complication in Graves' disease (GD) that causes disfigurement and sometimes blindness. The pathogenesis of GO remains unknown, while its symptoms demonstrate dependence between the thyroid gland and the orbit. The ongoing inflammatory process in retrobulbar tissue results in its remodeling characterized by increased volume of the orbital contents involving adipose tissue, with fibrosis and adipogenesis as predominant features. This study was aimed at the immunohistochemical verification of potential contribution and correlation between orbital expressions of IGF-1R, CD34, Foxp-3, PPAR-γ and CD4, CD68, TGF-ß, FGF-ß in severe and mild (long-lasting) GO. MATERIAL AND METHODS: Forty-one orbital tissue specimens - 22 patients with severe GO, 9 patients with mild GO and 10 patients undergoing blepharoplasty as a control group - were processed by routine immunohistochemistry. RESULTS: Increased IGF-1R, CD34 and Foxp-3 expression was found in both severe and mild GO, yet a significant correlation between CD34 and CD4, CD68, TGF-ß, FGF-ß expressions was observed in long-lasting GO. CONCLUSIONS: CD34 expression is proposed to be the marker of orbital tissue remodeling in the course of mild GO.

Association of PTPN22 polymorphism and its correlation with Graves' disease susceptibility in Polish adult population-A preliminary study.

BACKGROUND: Susceptibility to Graves' disease (GD) is determined by various genetic factors; the gene encoding protein tyrosine phosphatase (PTPN22) may be one of those associated with higher risk of GD. The aim was to estimate the association of the PTPN22 gene polymorphism rs2476601:c.C>T (c.1858C>T) with the predisposition to GD within the adult north-eastern Polish population. METHODS: PTPN22 gene polymorphism was analyzed in individuals with clinical GD history (n = 166) and healthy subjects (n = 154). The presence of different variants of the investigated gene polymorphism was estimated using the DNA Sanger sequencing method. RESULTS: Patients with GD had a more frequent occurrence of the T gene allele of PTPN22 gene compared to the control group, however, it was not significant (p = 0.257). Analysis of genotype distribution showed significantly more frequent occurrence of TT homozygote in GD patients compared to control individuals (p = 0.016, OR = 9.28). Patients with ophthalmopathy had a less frequent occurrence of the T gene allele of PTPN22 gene compared to patients without ophthalmopathy, however, it was not significant (p = 0.12). Occurrence of the T gene allele of PTPN22 gene in GD manifestation in those under 40-year old was more frequent compared to individuals over 40, but the obtained difference was also not significant (p = 0.75). CONCLUSIONS: Our preliminary study suggest that PTPN22:c.1858C>T gene polymorphism may be associated with a predisposition to GD within the adult north-eastern Polish population. The studied polymorphism of the PTPN22 gene did not significantly affect the risk of ophthalmopathy developing and disease manifestation before the age of 40.

Diagnostic power of VEGF, MMP-9 and TIMP-1 in patients with breast cancer. A multivariate statistical analysis with ROC curve.

PURPOSE: Vascular endothelial growth factor is an important factor in promoting angiogenesis in malignant processes, matrix metalloproteinase-9 in the degradation of extracellular matrix, which enhances metastasis, and tissue inhibitor of metalloproteinase-1 is its inhibitor. The aim of this study was to investigate the diagnostic power of these parameters in comparison to CA15-3 in breast cancer patients and in relation to the control group. MATERIALS/METHODS: The study included 120 breast cancer patients, 60 patients with benign breast tumors and 60 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA15-3 by chemiluminescent microparticle immuno assay. RESULTS: Tissue inhibitor of metalloproteinase-1 showed the highest value of sensitivity in breast cancer group (86.25%) and, more importantly, highest value in breast cancer stage I (85%). Vascular endothelial growth factor also showed high sensitivity (stage I and II-75%, III-85%, IV-70% and 76.25% in total breast cancer group) and the highest specificity (85%) from all tested parameters. It was also the only parameter which had statistically significant area under curve in all stages. In the total breast cancer group all tested parameters showed statistically significant area under curve, but the maximum range was obtained for combination: 'vascular endothelial growth factor + CA15-3'. Vascular endothelial growth factor seems to be the best candidate for diagnosing breast cancer stage I and for differentiating between breast cancer and non-carcinoma cases. CONCLUSIONS: The combined analysis of tested parameters and CA15-3 resulted in an increase in sensitivity and area under curve values, which provides hope for developing new panel of biomarkers that may be used in diagnosing breast cancer in the future.

Decreased Frequencies of Peripheral Blood CD4+CD25+CD127-Foxp3+ in Patients with Graves' Disease and Graves' Orbitopathy: Enhancing Effect of Insulin Growth Factor-1 on Treg Cells.

Graves' orbitopathy (GO) is characterized by orbital T cell infiltration. We evaluated the regulatory T (Treg) cell fractions induced with IGF-1 in Graves' disease (GD) with and without GO. Peripheral blood mononuclear cells (PBMCs) were obtained from 13 patients with GD without eye manifestations; 10 patients with active GO; and 12 patients with nodular goiter (NG). All the patients from GD, GO, and NG were subclinical hyperthyroid. We analyzed the expression of Treg cell markers (CD4, CD25, CD127-, Foxp3) on T cells and their ability to respond to IGF-1 stimulation. In patients with GD without GO, we found lowered percentages of CD4+ Foxp3+ cells, as compared to nodular goiter 1.77 vs. 5.42% (p=0.0276). Similarly, significantly reduced frequencies of CD4+CD25+CD127-Foxp3+ and CD4+CD25+CD127- cells were observed in GD patients as compared to nodular goiter patients with hyperthyreosis, (0.7 vs. 1.48%) (p=0.0071) and (14.5 vs. 37.2%) (p=0.0051), respectively. In GO with active GO, only the percentage of CD4+CD25+CD127- cells was found to be decreased versus nodular goiter (9.35 vs. 37.2) (p=0.0275). Stimulation of PBMC derived from GO patients with IGF-1 resulted in significant increase of frequency of both CD4+ Foxp3+ and CD4+CD25+CD127- Foxp3 cells. Decreased frequencies of peripheral blood CD4+CD25+CD127-Foxp3+ in patients with GD and GO could be an useful marker of autoimmune process and perhaps a possible target for future therapies. This is the first study demonstrating Treg-enhancing effects of IGF-1. Thus IGF-1 can be accounted for modulating Treg cell-related action in GO.

M-CSF in a new biomarker panel with HE4 and CA 125 in the diagnostics of epithelial ovarian cancer patients.

BACKGROUND: We investigated plasma levels of M-CSF and conventional tumor markers (HE4 and CA 125) in epithelial ovarian cancer patients as compared to control groups: benign ovarian tumor patients (cysts) and healthy subjects. METHODS: M-CSF levels were determined by ELISA, HE4 and CA 125 levels - by CMIA method. RESULTS: Our results have demonstrated significant differences in the concentration levels of M-CSF, CA 125 and HE4 between the groups of ovarian cancer patients, cysts patients and the healthy controls. In the groups tested M-CSF demonstrated equal to or higher values than both CA 125 and HE4 in diagnostic sensitivity (SE), positive and negative predictive values (PPV, NPV), and in the area under the ROC curve (AUC), particularly in the group with the serous epithelial sub-type of OC. Moreover, CA 125 showed better results of the aforementioned diagnostic criteria than HE4. The combined use of the parameters studied resulted in a further, significant increase in the value of the diagnostic indicators and in the value of the diagnostic power (AUC), especially in the early stages of ovarian cancer. CONCLUSIONS: These findings suggest a high usefulness of M-CSF in diagnosing the serous sub-type of epithelial ovarian cancer and in discriminating between cancer and non-carcinoma lesions, particularly in new diagnostic panels in combination with CA 125 and HE4 for the detection of EOC in the early stages.

Fundus albipunctatus: review of the literature and report of a novel RDH5 gene mutation affecting the invariant tyrosine (p.Tyr175Phe).

Fundus albipunctatus (FA) is a rare, congenital form of night blindness with rod system impairment, characterised by the presence of numerous small, white-yellow retinal lesions. FA belongs to a heterogenous group of so-called flecked retina syndromes. This disorder shows autosomal recessive inheritance and is caused mostly by mutations in the RDH5 gene. This gene encodes the enzyme that is a part of the visual cycle, the 11-cis retinol dehydrogenase. This study is a brief review of the literature on FA and a report of the first molecular evidence for RDH5 gene mutation in a Polish patient with this rare disorder. We present a novel pathogenic RDH5 gene mutation in a 16-year-old female patient with symptoms of night blindness. The patient underwent ophthalmological examinations, including colour vision testing, fundus photography, automated visual field testing, full-field electroretinography (ERG) and spectral optical coherent tomography (SOCT). The patient showed typical FA ERG records, the visual field was constricted and fundus examination revealed numerous characteristic, small, white-yellowish retinal lesions. DNA sequencing of the RDH5 gene coding sequence (exons 2-5) enabled the detection of the homozygous missense substitution c.524A > T (p.Tyr175Phe) in exon 3. This is the first report of RDH5 gene mutation that affects the invariant tyrosine, one of the most conserved amino acid residues in short-chain alcohol dehydrogenases/reductases (SDRs), crucial for these enzymes' activity. The location of this substitution, together with its predicted influence on the protein function, indicate that the p.Tyr175Phe mutation is the cause of FA in our patient.

Disturbances of modulating molecules (FOXP3, CTLA-4/CD28/B7, and CD40/CD40L) mRNA expressions in the orbital tissue from patients with severe graves' ophthalmopathy.

Purpose. To evaluate the relationship between the expression of orbital tissue mRNA for FOXP3, CTLA-4/CD28/CD80/CD86, and CD40/CD40 and the severity of Graves' orbitopathy (GO). Material and Methods. Orbital tissue was obtained from 26 patients with GO, with mild (n = 6) or severe GO (n = 20), and 7 healthy controls. The expression of mRNA of FOXP3, CTLA-4/CD28/CD80/CD86, CD40/CD40L was measured by RT-PCR. TCR and CD3 were evaluated by immunohistochemistry. Results. Higher mRNA for FoxP3 (relative expression: 1.4) and CD40 (1.27) and lower expression of CTLA-4 (0.61) were found in the GO tissues versus controls. In severe GO as compared to mild GO higher mRNA expression for FoxP3 (1.35) and CD40 (1.4) and lower expression for CTLA-4 (0.78), CD28 (0.62), and CD40L (0.56) were found. A positive correlation was found between FOXP3 mRNA and CD3 infiltration (R = 0.796, P = 0.0000001). Conclusions. The enhanced FOXP3 mRNA expression in GO samples may suggest the dysfunction of FOXP3 cells in the severe GO. The diminished mRNA expression of CTLA-4 in severe GO may indicate inadequate T regulatory function. The enhanced mRNA expression of CD40 in severe GO and negative correlation to CRP mRNA may suggest their role in the active and inactive GO.

Markers of inflammation and fibrosis in the orbital fat/connective tissue of patients with Graves' orbitopathy: clinical implications.

PURPOSE: To assess FGF-ß, TGF-ß, and COX2 expression and immunocompetent cells in the orbital tissue of patients with severe and mild Graves' orbitopathy. PATIENTS AND METHODS: Orbital tissue was taken from 27 patients with GO: (1) severe GO (n = 18), the mean clinical activity score (CAS) being 8.5 (SD 2.5); and (2) mild GO (n = 9), the mean CAS being 2.2 (SD 0.8), and from 10 individuals undergoing blepharoplasty. The expression of CD4+, CD8+, CD20+, and CD68 and FGF-ß, TGF-ß, and COX2 in the orbital tissue was evaluated by immunohistochemical methods. RESULTS: We demonstrated predominant CD4+ T cells in severe GO. CD68 expression was observed in the fibrous connective area of mild GO and was robust in severe GO, while the prominent TGF-ß expression was seen in all GO. Increased FGF-ß expression was observed in the fibroblasts and adipocytes of severe GO. No expression of COX2 was found in patients with GO. CONCLUSIONS: Macrophages and CD4 T lymphocytes are both engaged in the active/severe and long stage of inflammation in the orbital tissue. FGF-ß and TGF-ß expression may contribute to tissue remodeling, fibrosis, and perpetuation of inflammation in the orbital tissue of GO especially in severe GO.

Plasma levels of IL-17, VEGF, and adrenomedullin and S-cone dysfunction of the retina in children and adolescents without signs of retinopathy and with varied duration of diabetes.

The study objective was to assess chosen biochemical parameters of blood and bioelectric function of the retina in patients with T1DM. The study group consisted of 41 patients with T1DM with no signs of diabetic retinopathy. The control group included 21 pediatric patients. We performed (1) S-cone ERG testing with retina response stimulation in both eyes at the luminance of 0.1, 0.2, and 0.5 (cd × s/m(2)) with the 440 nm blue flash and light application of the amber background (300 ph cd/m(2), 495 nm wavelength), (2) anthropometric measurements, (3) biochemical investigations: IL-17, VEGF, and ADM by the ELISA method. A comparison of the ERG results with biochemical investigations indicates a likely correlation between the worsening of retinal bioelectric function and VEGF levels growing with diabetes duration. We showed a negative correlation between ADM and HbA1c and described possible causes of ADM reduction observed in subgroup I. We demonstrated the presence of bioelectric retinal dysfunction already before the diagnosis of diabetic retinopathy, which provides new possibilities in the diagnosis of preclinical chronic complications of diabetes. The changes observed in the levels of IL-17, ADM, and VEGF suggest their involvement in the diabetic pathogenesis of eye diseases.

Percentage of LFA-1+ and ICAM-1+ peripheral blood mononuclear cells in children and adolescents with type 1 diabetes does not distinguish patients with vascular complications.

There are only few studies evaluating lymphocytes activation in the diabetic vascular complications. ICAM-1/LFA-1 adhesion molecules not only participate in the lymphocyte T proliferation but also mediate leukocyte migration to the site of inflammation. We assess a relationship between the percentage of ICAM-1 and LFA-1 expressing PBMCs and the evolution of vascular complications in T1D in children and adolescents. The study was carried out on 60 children and adolescents with T1D (aged 9-20): (a) T1D lasting <5 years (n=20), (b) T1D lasting >5 years (n=20), without complications c) T1D lasting >5 years complicated with microalbuminuria, arterial hypertension, diabetic retinopathy (20 n). 20 healthy volunteers, age and sex matched constituted the control group. The expression of adhesion molecules was evaluated by using three-color flow cytometry. In children and adolescents with T1D <5 years, the percentage of ICAM-1+ and LFA-1+ PBMCs was decreased vs. controls (p<0.05 and p<0.001, respectively). Both in patients with T1D>5 years without vascular complications and in T1D with vascular disease the percentage of LFA-1+ T lymphocytes was significantly reduced in the peripheral blood (p<0.001 vs. healthy controls). In conclusion the percentage of LFA-1+ and ICAM-1+ PBMCs does not distinguish patients with vascular complications however decreased percentage of LFA-1+ PMBCs could serve as a nonspecific marker of the development of local inflammatory process in Type 1 diabetes.

Increased percentage of L-selectin+ and ICAM-1+ peripheral blood CD4+/CD8+ T cells in active Graves' ophthalmopathy.

The purpose of the study was to evaluate the percentage of CD4+/CD8+ peripheral T cells expressing CD62L+ and CD54+ in patients with Graves' disease and to assess if these estimations could be helpful as markers of active ophthalmopathy. The study was carried out in 25 patients with Graves' disease (GD) divided into 3 groups: 1/ 8 patients with active Graves' ophthalmopathy (GO) (CAS 3-6, GO complaints pound 1 year), 2/ 9 patients with hyperthyroid GD without symptoms of ophthalmopathy (GDtox) and 3/ 8 patients with euthyroid GD with no GO symptoms (GDeu). The control group consisted of 15 healthy volunteers age and sex matched to groups 1-3. The expression of lymphocyte adhesion molecules was evaluated by using three-color flow cytometry. In GO group the percentage of CD8+CD54+, CD8+CD62L+, CD4+CD54+ and CD4+CD62L+ T cells was significantly higher as compared to controls (p<0.001, p<0.05, p<0.01, p<0.001 respectively). The percentage of CD8+CD54+ T lymphocytes was also elevated in GO group in comparison to hyperthyroid GD patients (p< 0.05). CD4+CD62L+ and CD8+CD54+ percentages were also increased in GDtox and GDeu as compared to controls. We found a positive correlation between the TSHRab concentration and the percentage of CD8+CD62L+ T cells in all studied groups (r= 0.39, p<0.05) and between the TSHRab level and CAS (r= 0.77, p<0.05). The increased percentage of CD8+CD54+ and CD8+CD62L+ T cells in patients with Graves' ophthalmopathy may be used as a marker of immune inflammation activity.

Serum gelatinases (MMP-2 and MMP-9) and VCAM-1 as a guideline in a therapeutic approach in Graves' ophthalmopathy.

INTRODUCTION: The aim of this study was to estimate the influence of corticosteroids on soluble MMP-2, MMP-9 and VCAM-1 in patients with Graves ophthalmopathy (GO) in order to assess their usefulness as a guideline in a therapeutic approach. MATERIAL AND METHODS: Serum gelatinases and VCAM-1 were detected in three groups of subjects: 20 patients with GO (CAS > or = 3, anamnesis of GO > or = 1 yr), 12 patients with no clinical symptoms of ophthalmopathy (Gd) and 10 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions (2 series, 3 grams each time) of methylprednisolone (MP) and subsequent treatment with oral prednisone (60 mg per day) in a tapering schedule. The serum samples were collected 24 hours before MP, 24 hours after MP, after 14 days of treatment with prednisone and at the end of corticosteroid therapy. The levels of soluble MMP-2, MMP-9 and VCAM-1 were determined by the ELISA method. RESULTS: We have found no differences in serum MMP-2 between the groups studied and a significant reduction after MP only in corticosteroid-resistant GO patients. Soluble MMP-9 was highest in the GO group compared with both the Gd and control individuals. Moreover serum MMP-9 decreased in corticosteroid-responsive GO patients after MP and remained at the lower level at the end of the study. Positive correlations between MMP-2 and MMP-9 before and after MP administration were observed. Serum VCAM-1 was significantly elevated both in GO and Gd subjects and pre-treatment VCAM-1 levels were elevated in corticosteroid-responders compared with non-responders. CONCLUSIONS: Our results suggest that serum VCAM-1 may serve as a marker predicting the efficacy of corticosteroids and that soluble MMP-9 may be helpful in monitoring corticosteroid administration and in decision-making with regard to further GO treatment.

Pattern visual evoked potentials in the early diagnosis of optic neuropathy in the course of Graves' ophthalmopathy.

THE AIM OF THE STUDY: To investigate by means of pattern visual evoked potentials (PVEPs) early neuropathic changes in Graves' ophthalmopathy (GO) patients without any clinical symptoms of optic neuropathy in order to evaluate the prevalence of subclinical optic neuropathy in GO patients and to elucidate whether there is a relationship between PVEP (P100 and N75 latency), intraocular pressure (IOP) and exophthalmometry. MATERIAL AND METHODS: Two groups of patients were examined: 15 patients with GO without clinical signs of dysthyroid optic neuropathy (DON) and 12 healthy controls. The correlations between the N75 and P100 latencies, IOP and Hertel exophthalmometry were investigated. RESULTS: The mean PVEP N75 and P100 latencies were significantly delayed in the GO uncomplicated with DON in comparison with controls (LP100- 106.2 +/- 4.4 ms vs. 102.4 +/- 2.7 ms, p < 0.01 and LN75- 79.0 +/- 3.7 ms vs. 73.9 +/- 2.8 ms, p < 0.001). In GO patients we documented a positive correlation between the LN75 latency and exophthalmometric readings (R = 0.51; p < 0.01). The value of LP100 and LN75 was above the normal limit in 5/30 eyes (17%) and in 3/30 eyes (10%) respectively. CONCLUSIONS: The assessment of PVEPs (especially the P100 latency) in GO patients without clinical signs of DON is a useful tool for the early diagnosis of optic nerve involvement.

[Could the expression of L-selectin be an early marker of arterial hypertension and microangiopathy in the course of type 1 diabetes mellitus in juvenile patients?]. / Czy ekspresja L-selektyny moze byc wczesnym markerem nadcisnienia tetniczego i mikroangiopatii w przebiegu cukrzycy typu 1 u mlodocianych pacjentów?

BACKGROUND: Autoreactive T lymphocytes participate in the development of type 1 diabetes mellitus. The migration of T cells is initiated by increased expression of L-selectin on the cellular membrane of lymphocyte. Recently, a correlation between the concentration of sL-selectin and the develop-ment of diabetic retinopathy, atherosclerosis and arterial hypertension was stated. OBJECTIVES: The purpose of this study was to evaluate whether the expression of L-selectin on lymphocytes T alters in the course of the disease -- diabetes lasting less than 5 years and over 5 years; to assess a relationship between the percentage of L-selectin on T cells and the evolution of vascular complications; to elucidate whether the percentage of peripheral blood T lymphocytes expressing L-selectin could be an early marker of angiopathy in juvenile patients. MATERIAL AND METHODS: The study was carried out on 60 children and adolescents (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 a liquid chromatography technique HPLC-Variant (Bio-Rad). RESULTS: The percentage of T lymphocytes expressing L-selectin was significantly increased in all groups of patients with type 1 diabetes versus healthy controls (p<0.005 and p<0.001, in groups without complications and with angiopathy, respectively). Moreover in patients with diagnosed arterial hypertension the percentage of T lymphocytes expressing L-selectin was higher than in patients in whom arterial hypertension was not developed (p<0.05). CONCLUSIONS: In juvenile patients with type 1 diabetes the percentage of T lymphocytes expressing L-selectin was increased independently on the du-ration of the disease. In children with type 1 diabetes and diagnosed vascular complications the highest percentage of T lymphocytes expressing L-selectin was found.

[Hypertensive retinopathy in child with pheochromocytoma]. / Retinopatia nadcisnieniowa u dziecka z guzem chromochlonnym.

AIM: Pheochromocytoma is a tumor secreting catecholamines, it occurs in different age, rarely in children. The disorder coexists with malignant arterial hypertension. We present a case of patient with ophthalmic alterations in the course of pheochromocytoma. MATERIAL AND METHODS: In 12-year old boy operated on pheochromocytoma full ophthalmic examination, fluorescent angiography and ERG were performed. RESULTS: We found decreased visual acuity, hypertensive retinopathy and the scotopic and fotopic ERG alterations. CONCLUSIONS: Hypertensive retinopathy in the course of pheochromocytoma could be the first symptom of the disease, especially in children. The earlier this disorder is diagnosed and operated on, the better is the prognosis for health and regression of retinal findings.

[Pulsatile ocular blood flow in patients with juvenile glaucoma]. / Pulsacyjny przeplyw krwi w galce ocznej u pacjentów z jaskra mlodziencza.

PURPOSE: To compare ocular blood flow in patients with glaucoma juvenile and in normal subjects. MATERIAL AND METHODS: 20 glaucoma juvenile subjects and 20 persons as a control group aged 13 and 17, were matched for intraocular pressure and pulsatile ocular blood flow using pulsatile ocular blood flow (POBF). RESULTS: A positive correlation was found between ocular blood flow in patients with glaucoma juvenile and normal subjects. CONCLUSIONS: 1) POBF is a new and simple tool for the measurement intraocular pressure and pulsatile ocular blood flow and may be useful for diagnosis of the glaucoma. 2) We found a significant difference between ocular blood flow in glaucoma juvenile patients and normal subjects.

[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]. / Powierzchniowa ekspresja czasteczek kostymulujacych CD28/CTLA-4 na limfocytach T krwi obwodowej w przebiegu cukrzycy typu 1 u dzieci i mlodziezy.

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.