Search

Abstract Background Considerable progress was made by the introduction of interferon to the treatment of chronic hepatitis C virus infection. This treatment, however, is associated with the risk of developing or exacerbating autoimmune diseases, with chronic autoimmune thyroiditis being one of them. The aim of our study was to evaluate the predisposition to autoimmune thyroiditis in patients with chronic hepatitis C virus during IFN-alpha therapy, depending on the presence of polymorphisms in the promoter region of CTLA-4C (−318)T gene and in exon 1 of A49G gene as well as C1858T transition of PTPN22 gene. Methods The study was conducted in 149 patients aged between 18 and 70 years (mean of 43.9 years), including 82 men and 67 women. Control group for the assessment of the distribution of analyzed polymorphism of genotypes consisted of 200 neonates, from whom umbilical blood was drawn for the tests. The patients were divided into three groups: group 1 consisted of 114 patients without thyroid impairment before and during IFN-alpha therapy, group 2 contained 9 patients with AT with the onset prior to IFN-alpha treatment, and group 3 comprised 26 patients with AT starting after the beginning of IFN-alpha therapy. Results The frequency of C1858Tand C(−318)T genotypes observed in the study group did not differ significantly from control group. A significant difference, however, was found for A49G polymorphism. Conclusions No association was demonstrated between the occurrence of autoimmune thyroiditis with the onset during IFN-alpha therapy and the presence of polymorphisms within CTLA-4 C(−318)T gene in the promoter region and A49G in exon 1, as well as C1858T transition of PTPN22 gene.

Aim: To study an assessment of the number of enterochromaffin cells and expression of hydroxyindole-O-methyltransferase in colonic mucosa and urine excretion of 6-sulfatoxymelatonin in patients with ulcerative colitis., Methods: The study included 30 healthy subjects (group I-C), 30 patients with ulcerative proctitis [group II-ulcerative proctitis (UP)] and 30 patients with ulcerative colitis [group III-ulcerative colitis (UC)] in acute phases of these diseases. The number of enterochromaffin cells (EC) was estimated in rectal and colonic mucosa. Bioptates were assembled from many different parts of the large intestine. Immunorective cells collected from various parts of the colon were counted according to the Eurovision DAKO (Dako A/S, Copenhagen, Denmark) System in the range of 10 fields in each bioptate at × 200 magnification. The level of mRNA expression of hydroxyindole-O-methyltransferase (HIOMT) in colonic mucosa was estimated with RT-PCR. Urine 6-sulfatoxymelatonin (6-HMS) excretion was determined immunoenzymatically using an IBL (IBL International GmbH, Hamburg, Germany) kit (RE 54031)., Results: The number of EC cells in healthy subjects (C) was 132.40 ± 31.26. In patients of group II (UP) and group III (UC) the number of these cells was higher--225.40 ± 37.35 (P < 0.001) and--225.24 ± 40.50 (P < 0.001) respectively. Similar differences were related to HIOMT expression, which was 1.04 ± 0.36 in group C, 1.56 ± 0.56 (P < 0.01) in group UP and 2.00 ± 0.35 (P < 0.001) in group UC. Twenty-four hour 6-HMS urinary excretion was as follows: C--6.32 ± 4.95 μg/24 h, UP - 26.30 ± 7.29 μg/24 h (P < 0.01), UC--2.30 ± 12.56 μg/24 h (P < 0.001). A correlation between number of EC cells and 6-HMS excretion was noted in all groups: r = 0.766 in patients with UP, r = 0.703 with UC and r = 0.8551 in the control group; the correlation between the results is statistically significant., Conclusion: In the acute phases of both UP and UC, proliferation of EC cells and high expression of HIOMT and urine excretion of 6-HMS is noted. These changes may represent a beneficial response in the anti-inflammatory and defense mechanism.

Unlabelled: Enterochromaffin cells (EC) in gastric mucosa produce of serotonin and melatonin and trough its paracrine activity able to change motoric and secretory function. AIM OF OUR STUDIES: To evaluate the density of enterochromaffin cells in gastric mucosa in subjects with functional dyspepsia., Material and Methods: The investigations were performed in 50 subjects including 25 subjects with Postprandial Distress Syndrome and 25 subjects with Epigastric Pain Syndrome accordingly to Rome Criteria III. The comparative group comprised 25 healthy subjects. To identify enterochromaffin cells the bioptates were collected from the corpus and prepyloric part of the stomach and stained immunohistochemically., Results: Number of EC cells in corpus part were--healthy subjects 1.68 +/- 0.35, in patients with PDS--1.26 +/-0.37 (p < 0.001) and in EPS--2.11 +/- 0.43 (p < 0.01). In antrum Number of EC cells were: K--2.52 +/- 0.52, PDS--1.79 +/- 0.3 (p < 0.01), EPS--2.69 +/- 0.46 (p > 0.05). The results of urea breath test (UBT-13C) were: PDS--13.10 +/- 6.49% per hundred, EPS--18.98 +/- 10.11% per hundred (p < 0.05). In group of patients with EPS the positive correlation between number of enterochromaffin cells and urea breath test results was observed., Conclusions: The number of EC cells in gastric mucosa in subjects with functional dyspepsia is different than in healthy subjects. Evaluation of the number of enterochromaffin cells could have clinical value in differential diagnosis in functional dyspepsia.

Introduction: The aim of the study was to assess quality of life (QoL) in patients with infiltrative form of Graves' ophthalmopathy (GO) during the combined pulse treatment with methylprednisolone and orbital radiotherapy, and also to search for the relation between the results of ophthalmopathy treatment and changes in QoL., Material and Methods: The study involved 29 patients aged 25-74 (the mean age: 52 +/- 6 years) with infiltrative form of GO. They were classified for ophthalmopathy treatment on the basis of the following factors: the obtained euthyreosis, progressive character of eye changes, the level of eye changes determined on the basis of NO SPECS classification (at least class 3c), ophthalmopathy index (OI) according to Donaldson >or= 4. GO was diagnosed as active if CAS (clinical activity score) >or= 4. During the treatment, the patients received 6 cycles of methylprednisolone sodium succinate in doses of 1,0 g/24 h given as one-hour-long intravenous infusions for three successive days in a week. Between the 2nd and 4th cycle of Solu-Medrol, orbital radiotherapy with 10 MeV X-rays was performed. The control group was made up of healthy volunteers selected with regard to sex, age, educational background and nicotine addiction so as they corresponded with the study group. It involved 53 individuals aged 21-75 (the mean age: 52,4 +/- 14 years). QoL was assessed by means of the MOS SF-36 questionnaire., Results: Patients with GO evaluated their QoL lower than healthy individuals, which referred to physical functioning, physical and emotional role functioning, general health, vitality, social functioning, mental health and bodily pain. No correlation was found between quality of life and such factors as age, sex, or duration time of Graves disease and ophthalmopathy. Analogically, no relation was observed between the activity and stage of clinical development of eye changes and QoL. The use of the combined GO therapy contributed to a considerable decrease in the development of eye changes and the disease activity. After treatment, the patients' QoL improved which referred to physical role functioning, bodily pain, and vitality. Other QoL parameters did not statistically significantly differ., Conclusions: GO causes a considerable worsening of QoL. The stage of clinical development and activity of GO find no reflection in QoL. Effectiveness of treatment for GO cannot be evaluated on the basis of changes in QoL.

Unlabelled: The aim of the study was to assess influence of hyperthyroidism and glucocorticosteroid treatment on changes of bone turnover markers in patients with Graves' disease and thyroid ophthalmopathy (TO)., Material and Methods: Three groups of patients were included in the study. Group I was composed of 26 euthyroid Graves' disease patients with TO suitable for steroid treatment. Group II included 14 hyperthyroid Graves' patients without TO treated medically with anti-thyroid drugs. Group III (control group) included 20 healthy volunteers. Levels of the bone formation marker, i.e. bone-specific alkaline phosphatase (BALP) and the bone resorption marker, i.e. deoxypyridinoline (DPD) were measured in the group I before steroid treatment administration, after 3 methylprednisolone i.v. pulses and after completing the oral prednisone treatment. In the group II levels of BALP and DPD were assessed twice: before treatment of hyperthyroidism and after 6 months since euthyroid state had been achieved. In the group III levels of BALP and DPD were measured once in the basal conditions., Results: Mean initial levels of BALP in groups I and II did not differ significantly and were increased when compared to healthy volunteers. In the group I a transient significant decrease in BALP levels after 3 i.v. pulses of methylprednisolone was observed, followed by a significant increase in BALP after completing the oral prednisone therapy. The achievement of euthyroid state in Graves' patients (II) did not influence significantly BALP values. In the group I initial DPD levels were significantly lower than those in group II and higher than those in the control group (III). During steroid treatment of TO (group I) no dynamic changes of DPD levels were observed. The achievement of euthyroid state in group II was accompanied by a significant decrease in DPD levels, which were however than those in the control group., Conclusions: 1. In hyperthyroid state is associated with the profound stimulation of bone resorption, and to a lesser extent of bone formation. 2. The achievement of euthyroid state causes a rapid inhibition of bone resorption and maintains a compensatory stimulation of bone formation. 3. Glucocorticosteroid treatment with methylprednisolone i.v. pulses and orally administered prednisone do not influence significantly the processes of bone formation and bone resorption.

The aim of this study is to compare two different diagnostic methods (magnetic resonance imaging (MRI) and soluble forms of adhesion molecules: ICAM-1 and VCAM-1 measurement) in assessment of the activity of thyroid orbitopathy (TO) in patients with Graves' disease. 21 patients with infiltrative TO were treated with modified method by Bartalena et al. MRI scans and the measurement of soluble forms of ICAM-1 and VCAM-1 were performed before treatment, after methylprednisolone pulses along with radiotherapy of the retroorbital spaces and after the end of prednisone treatment. MRI scans did not reveal active stage of the disease in 4/21 patients with infiltrative TO, despite elevated levels of sICAM-1 and sVCAM-1. Patients both with active stage of the disease and with the results of MRJ scans revealing fibrotic changes in muscles responded well to therapy parallel with a significant decrease in levels of sICAM-1 and sVCAM-1. Levels of sVCAM-1 increased slightly under prednisone treatment despite improvement of clinical picture of TO, a significant decrease in sICAM-1 levels and in the number of muscles with active inflammatory process on MRI scans. In conclusion, serum levels of ICAM-1 seem to be more sensitive marker than MRI in assessment of the activity of TO. Concentrations of sVCAM-1 do not correspond with the clinical picture of the disease and the results of MRJ during treatment of TO.

Objective: An assessment of complications during systemic corticosteroid therapy combined with orbital radiotherapy in patients with thyroid eye disease., Material: 101 patients including 86 women and 15 men hospitalized in the Endocrinology Department of Pomeranian Medical Academy in 1999-2002., Methods: During the first stage of therapy, methylprednisolone in a daily dose of 1.0 g was administered intravenously for the following 3 days. The number of methylprednisolone pulses ranged from 3 up to 6-7. Orbital radiotherapy was usually performed between 2 and 4 pulse. Ten daily doses of 200 cGy were given in 2 weeks. After the series of methylprednisone and orbital radiotherapy had been finished, patients were treated with prednisone (Encorton, Polfa) given orally with an initial dose of 60 mg/day., Results: During the first stage of therapy carbohydrate metabolism disturbances were observed in 27 patients. Cardio-vascular complications were noted in 8 patients. Four patients complained of digestive tract dysfunction. Acute psychosis was diagnosed in 3 patients. Twelve patients developed infectious diseases. During prednisone administration, 1 case of bacterial pneumonia, 1 purulent meningitis and 1 schizophrenia onset were observed. In prolonged ophthalmologic follow-up 3/101 patients with cataract needed surgical treatment.

The aim of this study is to evaluate serum concentrations of sELAM-1 in patients with Graves' orbitopathy (GO). We studied levels of soluble form of E selectin -1 in patients with euthyroid progressive GO (group I) and euthyroid stable GO (group II), hyperthyroid Graves' disease (GD) without GO (group III) and in healthy controls (group IV). sELAM-1 levels were measured by ELISA method. The highest serum levels of sELAM-1 were found in group III. Mean sELAM-1 concentrations in patients with progressive and stable GO were slightly lower than those in group III patients. The sELAM-1 serum concentrations in group I and II were comparable, nearly the same despite the different clinical picture of the disease in both groups. Mean serum concentrations of sELAM-1 decreased significantly during treatment of progressive GO, parallel to the improvement of the eye changes. In conclusion, sELAM-1 concentrations do not reflect the degree of GO activity. A significant decrease in sELAM-1 concentrations are associated with the efficient outcome of treatment. Increased sELAM-1 levels seem to result form both GO and GD.

Unlabelled: The aim of the present study was to evaluate the efficiency of somatostatin analogue--lanreotide in the treatment of Graves ophthalmopathy. We examined the group of 6 women with thyroid eye disease in class 2 and 3 according to NO SPECS classification. Ophthalmopathy index and clinical activity score were above 3. Lanreotide was given in a dose of 30 mg i.m. every 2 weeks over a period of 3 months. The therapeutic effect was evaluated twice: 2 weeks after the end of lanreotide treatment (initial assessment) and after 2 years (final assessment). On initial assessment a decrease in ophthalmopathy index more than 2 points in each eye was observed. On follow up after 2 years we did not observe the worsening of thyroid eye disease., In Conclusion: lanreotide is an effective drug in reduction of soft tissue inflammatory changes in patients with active Graves ophthalmopathy. Absence of recurrence of the disease in final assessment indicates the persistent effect of lanreotide treatment.

Unlabelled: The aim of the present study is the assessment of efficacy of systemic corticosteroid treatment combined with orbital radiotherapy in patients with thyroid ophthalmopathy., Material: 101 patients hospitalized in the Endocrinology Department of the Pomeranian Medical University in the years 1999-2002., Methods: During first stage of treatment 3 to 6-7 intravenous pulses of methylprednisolone (SoluMedrol Pharmacia & Upjohn) in a dose of 1.0 g/day in consecutive 3 days were administered in combination with radiotherapy of the retroorbital spaces. Ten daily doses of 200 cGy using X-ray to each retroorbital space were given between the 2-nd to 4-th SoluMedrol pulse. Prednisone (Encorton Polfa) at an initial dose of 60 mg/day was used during the second stage of therapy., Results: Donaldson's ophthalmopathy index scored for each eye separately decreased significantly after both stages of treatment (right eye: 6.35 (before treatment); 2.25 (after first stage), 1.2 (after second stage), p<0.05; left eye: 6.1 (before treatment); 2.1 (after first stage); 1.15 (after second stage), p<0.05). The clinical picture of Graves ophthalmopahty after the end of therapy in most of patients was significantly improved. Persistent diplopia was found in 16/101 patients. Two of them were referred for surgical correction of abnormal eyeball fixation, the rest were using prismatic glasses. Until now, no recurrence of thyroid eye disease in treated patients was observed., Conclusions: Combined therapy is an effective method of treatment of Graves' ophtahlmopathy in terms of both rapid regression of inflammatory changes in orbital soft tissues and in prevention of recurrence of the disease.

The aim of this study is to evaluate serum concentrations of sVCAM-1 in patients with Graves' disease (GD) and thyroid associated orbitopathy (TAO). We measured serum sVCAM-1 levels in initially hyperthyroid GD patients without TAO, in patients with progressive and stable orbitopathy in euthyroid stage of GD and healthy controls. The highest serum concentrations of sVCAM-1 were observed in patients with hyperthyroid GD. In patients with euthyroid GD and progressive TAO, sVCAM-1 levels were slightly decreased than those in the group of patients with hyperthyroid GD and markedly elevated in comparison to the group of patients with stable TAO. In patients with hyperthyroid GD, sVCAM-1 concentrations dropped significantly after they had become euthyroid , but were still higher than those observed in group of patients with stable TAO and healthy people. Serum levels of sVCAM-1 in early stage of the progressive TAO (<6 m-ths) were higher than those in late stage of the disease (>6 m-ths), despite lower orbitopathy index (OI) found in early stage of the orbitopathy (<6 m-ths). In conclusion, both hyperhyroidism and TAO may contribute to elevated levels of sVCAM-1. A significant decrease in sVCAM-1 levels in initially hyperthyroid GD patients is associated with euthyroid stage of the disease. Concentrations of sVCAM-1 seem to correlate with the activity, not severity of progressive TAO.

It is known that body composition, especially body fat content, determines plasma leptin (LEP) levels. Clinical observation confirms that glucocorticoids (GS) have a considerable impact on body composition and body fat distribution which leads to visceral fat accumulation and a decrease in muscle mass in limbs. On the other hand, in experimental models GS stimulate ob mRNA expression in adipose tissue and LEP secretion into bloodstream. The aim of the study was to evaluate changes in body composition and fat and fat-free mass distribution in the conditions of endogenous hypercortisolism as well as to determine whether changes in body composition parameters may influence plasma LEP levels in patients with Cushing's syndrome (CUS). The study group was composed of 14 patients (12 F, 2 M) with ACTH-dependent and ACTH-independent CUS (BMI 29,5 +/- 1,0 kg/m2, aged 41,6 +/- 2,9 yrs.). The control group (KON) included 14 overweight/obese subjects (12 F, 2 M; WHR>0.8) matched for age, height, weight, and BMI with CUS group. Basal plasma LEP levels were measured by RIA kit. Total fat mass (BFM), fat-free mass (FFM), their regional depots (arms, legs, trunk) as well as bone mineral content (BMC) were determined by DEXA method (Lunar Co., USA). Values of BFM and %BF were comparable in both groups whereas the amount of FFM was lower in CUS group than in controls. Patients with CUS had less BF in limbs than controls whereas the difference in the amount of trunk BF in favour of CUS reached a borderline significance. Moreover, subjects with CUS exhibited decreased amount of FFM both in arms and legs when compared to controls, which may be explained by limb muscle and connective tissue wasting observed clinically. However, the amount of trunk FFM did not differ between both groups. Eventually, subjects with CUS had lower BMC values than controls. Absolute plasma LEP levels were 2-fold higher in CUS group than those in KON group (34,03 +/- 4,45 vs. 17,04 +/- 1,88, ng/ml; p=0.006), however, in both groups they were highly correlated with BFM and %BF. Multiple linear regression analysis revealed that in CUS group 64% of the variation of plasma LEP levels is explained by trunk BF and in KON group 92% of the variation of LEP levels is dependent of arms BF (+, 18%) and legs BF (+, 69%) and arms FFM (-, 5%). In conclusion, endogenous hypercortisolismus leads to the augmentation of truncal (visceral) fat accumulation as well as to a marked decrease in fat-free mass in limbs and in bone mineral content. In Cushing's syndrome, irrespectively of its cause (pituitary gland, adrenal glands), plasma LEP levels are elevated in relation to body fat content. Truncal (visceral) fat may have a relatively stronger influence on plasma LEP in Cushing's syndrome than in subjects with normal cortisolaemia, however, changes in body composition and tissue distribution do not fully account for the presence of markedly elevated LEP levels in this syndrome.

The authors studied serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) in patients with progressive Graves' ophthalmopathy (GO), stable GO, hyperthyroid Graves' disease (GD) without GO and in healthy controls. The highest serum concentrations of sICAM-1 were observed in patients with progressive GO. In patients with stable GO and GD mean serum levels of sICAM-1 were elevated to a lesser degree. Mean serum concentrations of sICAM-1 decreased significantly during treatment of patients with the progressive GO parallel to the improvement of the eye changes. In patients with hyperthyroid GD serum levels of sICAM-1 decreased significantly after they had become euthyroid. Mean sICAM-1 level in the euthyroid GD was markedly decreased in comparison to the group of patients with progressive GO and slightly elevated when compared to stable GO. In conclusion, serum levels of sICAM-1 seems to be a good parameter of disease activity in progressive infiltrative GO. The decrease in sICAM-1 concentrations in patients with the progressive GO closely corresponds to the improvement of the clinical picture of the progressive GO.

Excessive accumulation of hydrophilic glycosaminoglycans (GAG) in the retrobulbar tissue leads to many of the clinical manifestations of Graves' ophthalmopathy (GO). We examined the quantitative urinary GAG excretion in 35 patients with GO. GAG were isolated from 24-h urine collections by precipitation with cetylpyridinum chloride and ethanol according to Bitter. Patients with progressive ophthalmopathy showed on the average a twofold increase in urinary GAG excretion in comparison to patients with stable ophthalmopathy. The elevated values of GAG decreased significantly under treatment and correlated with the clinical picture of GO, however no correlation was found between the urinary GAG values and actual severity of ophthalmopathy classified according to Werner and Donaldson. There was no significant difference in GAG excretion between group 1, treated with methylprednisolon and irradiation of retrobulbar tissue and group 2, under therapy with methylprednisolon. In conclusion, elevated urinary GAG excretion is characteristic for the clinical picture of the progressive GO. The remarkable decrease in GAG values during treatment correlated to the positive response to immunosuppressive therapy.

Graves' ophthalmopathy (GO) is an autoimmune condition characterized by mononuclear cell infiltration of the extraocular muscles and/or orbital connective tissue. Adhesion molecules play an important role in the initiation and maintenance of the inflammatory immune process. Cellular activation and local expression of adhesion molecules lead to leucocyte recruitment, migration to inflammatory sites and targeting in the extravascular space. Vascular endothelium in retroocular connective tissues of patients with GO is strongly positive for EMAL-1 and VCAM-1, whereas VCAM-1 immunoreactivity is minimal and ELAM-1 immunoreactivity is generally absent in normal retroocular tissue. Interactions between matched activated T lymphocytes and orbital endothelial cells are mediated by integrin dependent ICAM-1/LFA-1 and VCAM-1/VLA-4 pathways and reveal marked differences when comparing GO orbital endothelial cells to normal ones. Higher soluble ICAM-1 volumes in patients with Graves' disease with GO than those in patients with Graves' disease without ophthalmopathy can reflect the degree of inflammatory activity. Increased soluble ELAM-1 concentration only in patients with GO suggests that soluble ELAM-1 could be a specific marker of endothelium activation in GO.

In decompensated liver cirrhosis, all effort should be made to maintain normal nutritional status so long as possible. Early nutritional assessment and dietetic intervention in the management of malnutrition, encephalopathy, ascites, infection and bleeding from gastrointestinal tract markedly decreases mortality and improves survival after liver transplantation in this group of patients.

Clinical and biochemical signs of protein-calorie malnutrition are associated with every liver disease. Malnutrition increases the number of complications and makes patient's prognosis worse. Early started specific treatment including nutritional support is an important medical strategy to limit malnutrition and to maintain liver functions. The author presents principles of nutritional treatment in stable liver cirrhosis.

Callosal afferents to the primary visual cortex (area Oc1) mainly originate in the border region between the lateral portion of the primary visual cortex (area Oc1) and the laterally positioned secondary visual cortex (area Oc2L) of the contralateral hemisphere. The extent of this region has been determined by retrograde labeling with horseradish peroxidase (HRP). In normal rats the width of the retrogradely labeled cortical strip is about 0.3 mm. In rats monocularly enucleated from the 23rd up to the 44th ontogenetic day and subsequently injected as adults with HRP into Oc1 ipsilateral to the remaining eye, the perikarya of the callosal afferents from the opposite hemisphere are labeled in the form of significantly wider columns (about 0.8 mm) than in animals enucleated from the 50th ontogenetic day onwards. The latter do not differ from controls.