Activating point mutation of the BRAF gene, the most common genetic alteration reported in papill... more Activating point mutation of the BRAF gene, the most common genetic alteration reported in papillary thyroid carcinomas (PTC), has been associated with poor prognostic characteristics. Our objective was to determine the frequency of BRAFV600E mutation in PTC tumor tissues from the period 1960-2007 and to correlate it with clinicopathological parameters. DNAs were extracted from 242 PTCs, 23 sporadic medullary carcinomas, one anaplastic carcinoma and 6 poorly differentiated carcinomas. The presence of BRAFV600E mutation was determined using single strand conformation polymorphism method and verified by direct sequencing. BRAFV600E mutation was detected in 81 of 242 PTCs (33.5%), in one of 6 poorly differentiated carcinomas (16.7%) and in anaplastic carcinoma. BRAFV600E mutation was much less frequent in the follicular variant compared to classical variant and mixed follicular- classical variant of PTCs (p=0.001). BRAFV600E mutation was significantly associated with presence of nodal metastasis (p=0.029), more advanced TNM stage (p=0.014) and recurrence of disease (p=0.008). The mutation correlated with a higher age at diagnosis (p=0.049) and with a greater tumor size (p=0.041). Multivariate analysis confirmed these findings. The prevalence of BRAFV600E mutation before 1986 was significantly lower than after it (p=0.008). Our data suggest that BRAFV600E mutation is associated with high-risk clinicopathological characteristics of PTC and worse prognosis of patients. The frequency of the mutation significantly varied during the observed period but rather because of the different age distribution of patients in particular periods than as a consequence of Chernobyl accident.
Experimental and Clinical Endocrinology & Diabetes, 2006
Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer representing about 10% of all ... more Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer representing about 10% of all thyroid malignancies. It occurs mostly as a sporadic tumor or in association with autosomal dominant inherited cancer syndromes--multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Germline mutations in exons 8, 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene are found in most of the familial cases. There are only a few published data reporting multiple germline mutations in the RET proto-oncogene. We have detected double germline mutations in 2 different exons on the same RET allele in two MEN 2 families. In the MEN 2A family, double germline mutation in exons 10 (Cys620Phe) and 13 (Tyr791Phe) was detected. In the MEN 2B family, beside the classical germline mutation in exon 16 (Met918Thr) a second germline mutation in exon 13 (Tyr791Phe) was found. This study revealed that MEN 2 syndromes can also be caused by double germline mutations in the RET proto-oncogene and these families can be added to small worldwide cohort of families with multiple germline mutations.
Fine needle aspiration cytology (FNAC) of the thyroid gland is a well-established method. However... more Fine needle aspiration cytology (FNAC) of the thyroid gland is a well-established method. However, it has inherent limitations, especially in the diagnosis of follicular and oncocytic tumours and in distinguishing between nuclear atypia in colloid goitre with regressive changes and cystic papillary carcinoma. The aim of our study was to evaluate dipeptidyl peptidase IV (DPP IV) as a marker of malignancy in FNAC. We tested 254 thyroid specimens (intraoperative imprint smears) for DPP IV. The sensitivity was 71%, the specificity was 96%, and the diagnostic accuracy was 93%, respectively, with a threshold of 50% of positive cells. To the best of our knowledge it is the largest histologically confirmed study reported in the literature. We suggest the assessment of DPP IV as an adjunct diagnostic marker of malignancy in thyroid specimens suspicious of papillary carcinoma. However, the value of the marker in follicular lesions is very limited.
information system still collects simple data. The press release that accompanies the Department ... more information system still collects simple data. The press release that accompanies the Department of Health and Social Security's bulletin misleads when it suggests that activity represents quality. It does no such thing. The DHSS should be more aware of the need to measure effectiveness of health service activities to encourage improvement in the quality of health care.
Incretin hormones are peptides that are secreted from endocrine cell of gastrointestinal tract af... more Incretin hormones are peptides that are secreted from endocrine cell of gastrointestinal tract after nutrient ingestion and stimulate insulin secretion. Glucosodependent Insulinotropic Peptide--GIP is released from K-cells of duodenum and proximal jejunum, recently GIP synthesis has been proved in pancreatic alpha cells. Besides the incretin effect causes GIP increased lipogenesis and decreased lipolysis in fat tissue, increased bone formation and decreased resorption and has protective and proliferative effect on CNS neurons. Both GIP agonists (to treat diabetes) and antagonist (to treat obesity) are being studied. Another incretin hormone is derived in intestinal I-cells by posttranslational processing of proglucagon--glucagon-like peptides 1 and 2 (GLP-1 and GLP-2). GLP-1 stimulates insuline production and inhibits glucagon secretion, exerts proliferative and antiapoptotic effect on beta-cells. Via receptors on vagal nerve and central mechanisms decreases food intake and decrease...
Morphological diagnostics of thyroid gland tumours faces certain differential diagnostic problems... more Morphological diagnostics of thyroid gland tumours faces certain differential diagnostic problems. Extensive histological examination of the entire tumour is required for the final diagnosis of follicular and oncocytic tumours. Thus, assessment of reliable definitive cytological and/or intraoperative histological diagnosis is not possible. No marker of malignancy has been so far generally accepted in the thyroid tumour diagnosis. The aim of the study was to evaluate membrane protease dipeptidyl peptidase IV (DPP IV) in the differential diagnosis of thyroid tumours. DPP IV was assessed cytochemically in 254 smears, histochemically in 314 cryostat sections, and immunohistochemically in 309 paraffin-embedded sections obtained from the group of 336 patients. There were 283 females and 53 males with the mean age of 48 years (range 15-80 years) in this series. Sensitivity of cytochemical detection was 71%, specificity was 96%, and diagnostic accuracy was 93% using the 50% threshold. Histo...
Low testosterone level is common in obese men and even more frequent in the presence of type 2 di... more Low testosterone level is common in obese men and even more frequent in the presence of type 2 diabetes mellitus. Low testosterone level is probably not caused by increased aromatization of testosterone to estradiol in fat tissue. Increase of inflammation mediators, insulin and leptin resistance and low SHBG level may play more important role. Low testosterone level may manifest with low libido, erectile dysfunction, fatigue and depressive mood; it has a role in development of anaemia, osteoporosis, worsening of insulin resistance and it is probably marker of increased all-case and cardiovascular mortality. Routine investigation of testosterone level is indicated in every man with type 2 diabetes mellitus. As in non-diabetic men of middle and higher age substitution is indicated only in presence of clinical symptoms of hypogonadism. The substitution improves mainly libido, erectile dysfunction is influenced less. However, the phosphodiasterase-5 inhibitors efficiency is markedly imp...
Endocrine impairment is more common in patients with diabetes than in general population. Both hy... more Endocrine impairment is more common in patients with diabetes than in general population. Both hyper- and hypothyroidism increases cardiovascular morbidity and mortality. Subclinical hypothyroidism is a risk factor for coronary hearth disease in patients younger than 65 years. In elderly is its influence questionable or even preventive and the benefit of substitution should be weighted against the risks. Treatment with glucocorticoids in a dose of 7.5 mg methylprednisolone and higher considerably increases risk of vascular impairment. Patients cured from endogenous Cushing's syndrome maintain increased cardiovascular risk factors and structural changes of vessels. Subclinical hypercortisolism seems to have little effect. Growth hormone (GH) insufficiency increases cardiovascular risks and contributes to increased mortality of these patients. To the contrary increased GH production in acromegaly effect more heart than vessels. Hypogonadism is established risk factor for ischemic ...
As diabetes mellitus type 1 is part of the polyglandular autoimmune syndrome it is no wonder that... more As diabetes mellitus type 1 is part of the polyglandular autoimmune syndrome it is no wonder that autoimmune disorders of the thyroid are in diabetics about five times more common and adrenal insufficiency four times more common than in general population. Manifest hypothyroidism leads to the decrease in insulin sensitivity and increase of glucose stimulated insulin secretion. These changes are reversible by substitution. Even subclinical hypothyroidism increases demand on pancreatic beta cell. The glucocorticoid insufficiency causes marked increase of insulin sensitivity, decrease of endogenous glucose production and increase of glucose oxidation. Synthetic thyroxin is optimal for thyroid hormones substitution. Combined substitution with trijodthyronin did not proved to have any beneficial effect. The basis of substitution in adrenal insufficiency is replacement of hydrocortisone in doses that do not have negative metabolic effects. Preparations available today do not allow imitati...
The immunohistochemical expression of galectin-3 (Gal3), cytokeratin 19 (CK19), neural cell adhes... more The immunohistochemical expression of galectin-3 (Gal3), cytokeratin 19 (CK19), neural cell adhesion molecule (NCAM), and E-cadherin (Ecad) was evaluated to assess their use in diagnostics of papillary thyroid carcinoma (PTC). A total of 84 PTCs - 36 classical variants (cPTCs), 26 follicular variants (fPTCs), and 22 papillary microcarcinomas (mPTCs) were studied. Expression of Gal3 was found in 36/36 (100%) cPTCs, 24/26 (92%) fPTCs, and 19/22 (86%) mPTCs. CK19 expression was detected in 34/36 (94%) cPTCs, 17/26 (65%) fPTCs, and 13/22 (59%) mPTCs. Expression of NCAM was seen in 5/36 (14%) cPTCs, 7/26 (27%) fPTCs, and 9/22 (41%) mPTCs. Ecad expression was found in 23/36 (64%) cPTCs, 17/26 (65%) fPTCs, and 18/22 (82%) mPTCs. A significant difference in CK19 expression was observed between cPTC and both fPTC and mPTC (p < 0.001). Furthermore, extrathyroid tumor spread significantly correlated with both level of CK19 expression and loss of Ecad expression (p = 0.001, p = 0.04). Our fi...
Thyroid-associated ophthalmopathy (TAO) is an inflammatory process associated with autoimmune thy... more Thyroid-associated ophthalmopathy (TAO) is an inflammatory process associated with autoimmune thyroid diseases (AITD), most commonly Graves disease. It is clinically present in up to one half of patients suffering with AITD and 3-5 % of patients suffer from intense pain and inflammation with double vision or even loss of vision. Because diabetes mellitus type 1 and AITD have similar pathogenesis and shared genetic background it is not surprising that up to 30% of patients with type 1 diabetes develop AITD during long term follow-up. It is important to consider the activity and severity ofTAO separately. Treatment is effective at the beginning of disease in the high activity phase. Glucocorticoids represent a milestone in the treatment of TAO and are necessary in diabetic patients as well. According to the latest experience the most effective and best tolerated regimen is iv glucocorticoid administration of methylprednisolone at weekly intervals up to a cumulative dose of 4.5 g. Orbi...
Physiological research / Academia Scientiarum Bohemoslovaca, 2008
Ionizing radiation and somatostatin analogues are used for acromegaly treatment to achieve normal... more Ionizing radiation and somatostatin analogues are used for acromegaly treatment to achieve normalization or reduction of growth hormone hypersecretion and tumor shrinkage. In this study, we investigated a combination of somatostatin (SS14) with ionizing radiation of (60)Co and its effect on reparation of radiation-induced damage and cell death of somatomammotroph pituitary cells GH3. Doses of gamma-radiation 20-50 Gy were shown to inhibit proliferation and induce apoptosis in GH3 cells regardless of somatostatin presence. It has been found that the D(0) value for GH3 cells was 2.5 Gy. Somatostatin treatment increased radiosensitivity of GH3 cells, so that D(0) value decreased to 2.2 Gy. We detected quick phosphorylation of histone H2A.X upon irradiation by the dose 20 Gy and its colocalization with phosphorylated protein Nbs-1 in the site of double strand break of DNA (DSB). Number of DSB decreased significantly 24 h after irradiation, however, clearly distinguished foci persisted, ...
Traumatic brain injury represents major medical and social problem in all developed countries. It... more Traumatic brain injury represents major medical and social problem in all developed countries. Its incidence is about 200 per 100,000 inhabitants per year. In the acute phase immediately after injury the posterior pituitary dysfunction is well-known. The incidence of severe grossly hypernatremic cases of diabetes insipidus (DI) is about 3%, less severe form of ADH insufficiency was recognized in 21-26%. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was described in about 14%. These changes are transient in most cases, persisting DI has an incidence of 5-7% and SIADH cases recover almost always. Since the beginning of this century several series evaluating prospectively all patients after moderate to severe TBI have been published. Permanent hypopituitarism was found in one quarter to one half of them. The most common turned out to be the growth hormone (17.6%) and gonadotropic (13.4%) deficiency. Less common is the corticotropic (8.4%) and thyrotropic (4.3%) i...
Active acromegaly deteriorates the quality of life and shortens the life expectancy. Surgery is t... more Active acromegaly deteriorates the quality of life and shortens the life expectancy. Surgery is the first-line therapy in the majority of patients, followed by radiotherapy in unsuccessful cases. The surgery cure rate is only one half in the case of macroadenomas and it takes years before radiotherapy normalizes GH and IGF-I levels. In the interim, medical therapy is necessary. Second-generation dopamine agonists (cabergoline) are successful in about one third of patients, especially in those with lower basal IGF-I levels and with adenomas co-secreting prolactin. Somatostatin analogues octreotide and lanreotide are the gold standard of medical treatment - both are available in a form applicable as once-monthly injections. They successfully control disease activity in the majority of patients and induce tumour shrinkage in part of adenomas. Surgical debunking of macroadenomas improves the results of therapy with somatostatin analogues and it is not necessary to discontinue this thera...
The authors describe a female patient with large parathyroid gland adenoma presenting with clinic... more The authors describe a female patient with large parathyroid gland adenoma presenting with clinical symptoms of primary hyperparathyroidism and severe hypercalcaemia. Before planned surgical treatment the patient spontaneously developed clinical symptoms of tetany. Hypocalcaemia was confirmed by laboratory test. The reason turned out to be spontaneous necrosis of the parathyroid adenoma, resulting in remission of hyperparathyroidism. After stabilization of calcium levels, the necrotic adenoma was removed and histopathological examination revealed necrotic adenoma with only occasional vital adenoma cells. During the next follow-up the patient was without any subjective complaints and her state was stable. This phenomenon, yet described in the literature in past, belongs to unusual findings.
Human thyroid peroxidase (hTPO) is a membrane protein with a key role in the thyroid hormones syn... more Human thyroid peroxidase (hTPO) is a membrane protein with a key role in the thyroid hormones synthesis. Loss of hTPO was described in malignant tumours of the thyroid gland. hTPO was tested as a marker of malignancy. Immunohistochemical study of hTPO in 321 thyroid lesions (45 malignant tumours, 72 benign tumours, 199 benign non-tumours lesions, and 5 normal thyroid glands) is presented. The sensitivity of hTPO in predicting malignancy in thyroid is 64%, and the specificity is 87%. Thus, hTPO is of limited value in the diagnosis of thyroid malignancy. The authors discuss the role of hTPO as a marker of differentiation.
Activating point mutation of the BRAF gene, the most common genetic alteration reported in papill... more Activating point mutation of the BRAF gene, the most common genetic alteration reported in papillary thyroid carcinomas (PTC), has been associated with poor prognostic characteristics. Our objective was to determine the frequency of BRAFV600E mutation in PTC tumor tissues from the period 1960-2007 and to correlate it with clinicopathological parameters. DNAs were extracted from 242 PTCs, 23 sporadic medullary carcinomas, one anaplastic carcinoma and 6 poorly differentiated carcinomas. The presence of BRAFV600E mutation was determined using single strand conformation polymorphism method and verified by direct sequencing. BRAFV600E mutation was detected in 81 of 242 PTCs (33.5%), in one of 6 poorly differentiated carcinomas (16.7%) and in anaplastic carcinoma. BRAFV600E mutation was much less frequent in the follicular variant compared to classical variant and mixed follicular- classical variant of PTCs (p=0.001). BRAFV600E mutation was significantly associated with presence of nodal metastasis (p=0.029), more advanced TNM stage (p=0.014) and recurrence of disease (p=0.008). The mutation correlated with a higher age at diagnosis (p=0.049) and with a greater tumor size (p=0.041). Multivariate analysis confirmed these findings. The prevalence of BRAFV600E mutation before 1986 was significantly lower than after it (p=0.008). Our data suggest that BRAFV600E mutation is associated with high-risk clinicopathological characteristics of PTC and worse prognosis of patients. The frequency of the mutation significantly varied during the observed period but rather because of the different age distribution of patients in particular periods than as a consequence of Chernobyl accident.
Experimental and Clinical Endocrinology & Diabetes, 2006
Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer representing about 10% of all ... more Medullary thyroid carcinoma (MTC) is a rare form of thyroid cancer representing about 10% of all thyroid malignancies. It occurs mostly as a sporadic tumor or in association with autosomal dominant inherited cancer syndromes--multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC. Germline mutations in exons 8, 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene are found in most of the familial cases. There are only a few published data reporting multiple germline mutations in the RET proto-oncogene. We have detected double germline mutations in 2 different exons on the same RET allele in two MEN 2 families. In the MEN 2A family, double germline mutation in exons 10 (Cys620Phe) and 13 (Tyr791Phe) was detected. In the MEN 2B family, beside the classical germline mutation in exon 16 (Met918Thr) a second germline mutation in exon 13 (Tyr791Phe) was found. This study revealed that MEN 2 syndromes can also be caused by double germline mutations in the RET proto-oncogene and these families can be added to small worldwide cohort of families with multiple germline mutations.
Fine needle aspiration cytology (FNAC) of the thyroid gland is a well-established method. However... more Fine needle aspiration cytology (FNAC) of the thyroid gland is a well-established method. However, it has inherent limitations, especially in the diagnosis of follicular and oncocytic tumours and in distinguishing between nuclear atypia in colloid goitre with regressive changes and cystic papillary carcinoma. The aim of our study was to evaluate dipeptidyl peptidase IV (DPP IV) as a marker of malignancy in FNAC. We tested 254 thyroid specimens (intraoperative imprint smears) for DPP IV. The sensitivity was 71%, the specificity was 96%, and the diagnostic accuracy was 93%, respectively, with a threshold of 50% of positive cells. To the best of our knowledge it is the largest histologically confirmed study reported in the literature. We suggest the assessment of DPP IV as an adjunct diagnostic marker of malignancy in thyroid specimens suspicious of papillary carcinoma. However, the value of the marker in follicular lesions is very limited.
information system still collects simple data. The press release that accompanies the Department ... more information system still collects simple data. The press release that accompanies the Department of Health and Social Security's bulletin misleads when it suggests that activity represents quality. It does no such thing. The DHSS should be more aware of the need to measure effectiveness of health service activities to encourage improvement in the quality of health care.
Incretin hormones are peptides that are secreted from endocrine cell of gastrointestinal tract af... more Incretin hormones are peptides that are secreted from endocrine cell of gastrointestinal tract after nutrient ingestion and stimulate insulin secretion. Glucosodependent Insulinotropic Peptide--GIP is released from K-cells of duodenum and proximal jejunum, recently GIP synthesis has been proved in pancreatic alpha cells. Besides the incretin effect causes GIP increased lipogenesis and decreased lipolysis in fat tissue, increased bone formation and decreased resorption and has protective and proliferative effect on CNS neurons. Both GIP agonists (to treat diabetes) and antagonist (to treat obesity) are being studied. Another incretin hormone is derived in intestinal I-cells by posttranslational processing of proglucagon--glucagon-like peptides 1 and 2 (GLP-1 and GLP-2). GLP-1 stimulates insuline production and inhibits glucagon secretion, exerts proliferative and antiapoptotic effect on beta-cells. Via receptors on vagal nerve and central mechanisms decreases food intake and decrease...
Morphological diagnostics of thyroid gland tumours faces certain differential diagnostic problems... more Morphological diagnostics of thyroid gland tumours faces certain differential diagnostic problems. Extensive histological examination of the entire tumour is required for the final diagnosis of follicular and oncocytic tumours. Thus, assessment of reliable definitive cytological and/or intraoperative histological diagnosis is not possible. No marker of malignancy has been so far generally accepted in the thyroid tumour diagnosis. The aim of the study was to evaluate membrane protease dipeptidyl peptidase IV (DPP IV) in the differential diagnosis of thyroid tumours. DPP IV was assessed cytochemically in 254 smears, histochemically in 314 cryostat sections, and immunohistochemically in 309 paraffin-embedded sections obtained from the group of 336 patients. There were 283 females and 53 males with the mean age of 48 years (range 15-80 years) in this series. Sensitivity of cytochemical detection was 71%, specificity was 96%, and diagnostic accuracy was 93% using the 50% threshold. Histo...
Low testosterone level is common in obese men and even more frequent in the presence of type 2 di... more Low testosterone level is common in obese men and even more frequent in the presence of type 2 diabetes mellitus. Low testosterone level is probably not caused by increased aromatization of testosterone to estradiol in fat tissue. Increase of inflammation mediators, insulin and leptin resistance and low SHBG level may play more important role. Low testosterone level may manifest with low libido, erectile dysfunction, fatigue and depressive mood; it has a role in development of anaemia, osteoporosis, worsening of insulin resistance and it is probably marker of increased all-case and cardiovascular mortality. Routine investigation of testosterone level is indicated in every man with type 2 diabetes mellitus. As in non-diabetic men of middle and higher age substitution is indicated only in presence of clinical symptoms of hypogonadism. The substitution improves mainly libido, erectile dysfunction is influenced less. However, the phosphodiasterase-5 inhibitors efficiency is markedly imp...
Endocrine impairment is more common in patients with diabetes than in general population. Both hy... more Endocrine impairment is more common in patients with diabetes than in general population. Both hyper- and hypothyroidism increases cardiovascular morbidity and mortality. Subclinical hypothyroidism is a risk factor for coronary hearth disease in patients younger than 65 years. In elderly is its influence questionable or even preventive and the benefit of substitution should be weighted against the risks. Treatment with glucocorticoids in a dose of 7.5 mg methylprednisolone and higher considerably increases risk of vascular impairment. Patients cured from endogenous Cushing's syndrome maintain increased cardiovascular risk factors and structural changes of vessels. Subclinical hypercortisolism seems to have little effect. Growth hormone (GH) insufficiency increases cardiovascular risks and contributes to increased mortality of these patients. To the contrary increased GH production in acromegaly effect more heart than vessels. Hypogonadism is established risk factor for ischemic ...
As diabetes mellitus type 1 is part of the polyglandular autoimmune syndrome it is no wonder that... more As diabetes mellitus type 1 is part of the polyglandular autoimmune syndrome it is no wonder that autoimmune disorders of the thyroid are in diabetics about five times more common and adrenal insufficiency four times more common than in general population. Manifest hypothyroidism leads to the decrease in insulin sensitivity and increase of glucose stimulated insulin secretion. These changes are reversible by substitution. Even subclinical hypothyroidism increases demand on pancreatic beta cell. The glucocorticoid insufficiency causes marked increase of insulin sensitivity, decrease of endogenous glucose production and increase of glucose oxidation. Synthetic thyroxin is optimal for thyroid hormones substitution. Combined substitution with trijodthyronin did not proved to have any beneficial effect. The basis of substitution in adrenal insufficiency is replacement of hydrocortisone in doses that do not have negative metabolic effects. Preparations available today do not allow imitati...
The immunohistochemical expression of galectin-3 (Gal3), cytokeratin 19 (CK19), neural cell adhes... more The immunohistochemical expression of galectin-3 (Gal3), cytokeratin 19 (CK19), neural cell adhesion molecule (NCAM), and E-cadherin (Ecad) was evaluated to assess their use in diagnostics of papillary thyroid carcinoma (PTC). A total of 84 PTCs - 36 classical variants (cPTCs), 26 follicular variants (fPTCs), and 22 papillary microcarcinomas (mPTCs) were studied. Expression of Gal3 was found in 36/36 (100%) cPTCs, 24/26 (92%) fPTCs, and 19/22 (86%) mPTCs. CK19 expression was detected in 34/36 (94%) cPTCs, 17/26 (65%) fPTCs, and 13/22 (59%) mPTCs. Expression of NCAM was seen in 5/36 (14%) cPTCs, 7/26 (27%) fPTCs, and 9/22 (41%) mPTCs. Ecad expression was found in 23/36 (64%) cPTCs, 17/26 (65%) fPTCs, and 18/22 (82%) mPTCs. A significant difference in CK19 expression was observed between cPTC and both fPTC and mPTC (p < 0.001). Furthermore, extrathyroid tumor spread significantly correlated with both level of CK19 expression and loss of Ecad expression (p = 0.001, p = 0.04). Our fi...
Thyroid-associated ophthalmopathy (TAO) is an inflammatory process associated with autoimmune thy... more Thyroid-associated ophthalmopathy (TAO) is an inflammatory process associated with autoimmune thyroid diseases (AITD), most commonly Graves disease. It is clinically present in up to one half of patients suffering with AITD and 3-5 % of patients suffer from intense pain and inflammation with double vision or even loss of vision. Because diabetes mellitus type 1 and AITD have similar pathogenesis and shared genetic background it is not surprising that up to 30% of patients with type 1 diabetes develop AITD during long term follow-up. It is important to consider the activity and severity ofTAO separately. Treatment is effective at the beginning of disease in the high activity phase. Glucocorticoids represent a milestone in the treatment of TAO and are necessary in diabetic patients as well. According to the latest experience the most effective and best tolerated regimen is iv glucocorticoid administration of methylprednisolone at weekly intervals up to a cumulative dose of 4.5 g. Orbi...
Physiological research / Academia Scientiarum Bohemoslovaca, 2008
Ionizing radiation and somatostatin analogues are used for acromegaly treatment to achieve normal... more Ionizing radiation and somatostatin analogues are used for acromegaly treatment to achieve normalization or reduction of growth hormone hypersecretion and tumor shrinkage. In this study, we investigated a combination of somatostatin (SS14) with ionizing radiation of (60)Co and its effect on reparation of radiation-induced damage and cell death of somatomammotroph pituitary cells GH3. Doses of gamma-radiation 20-50 Gy were shown to inhibit proliferation and induce apoptosis in GH3 cells regardless of somatostatin presence. It has been found that the D(0) value for GH3 cells was 2.5 Gy. Somatostatin treatment increased radiosensitivity of GH3 cells, so that D(0) value decreased to 2.2 Gy. We detected quick phosphorylation of histone H2A.X upon irradiation by the dose 20 Gy and its colocalization with phosphorylated protein Nbs-1 in the site of double strand break of DNA (DSB). Number of DSB decreased significantly 24 h after irradiation, however, clearly distinguished foci persisted, ...
Traumatic brain injury represents major medical and social problem in all developed countries. It... more Traumatic brain injury represents major medical and social problem in all developed countries. Its incidence is about 200 per 100,000 inhabitants per year. In the acute phase immediately after injury the posterior pituitary dysfunction is well-known. The incidence of severe grossly hypernatremic cases of diabetes insipidus (DI) is about 3%, less severe form of ADH insufficiency was recognized in 21-26%. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) was described in about 14%. These changes are transient in most cases, persisting DI has an incidence of 5-7% and SIADH cases recover almost always. Since the beginning of this century several series evaluating prospectively all patients after moderate to severe TBI have been published. Permanent hypopituitarism was found in one quarter to one half of them. The most common turned out to be the growth hormone (17.6%) and gonadotropic (13.4%) deficiency. Less common is the corticotropic (8.4%) and thyrotropic (4.3%) i...
Active acromegaly deteriorates the quality of life and shortens the life expectancy. Surgery is t... more Active acromegaly deteriorates the quality of life and shortens the life expectancy. Surgery is the first-line therapy in the majority of patients, followed by radiotherapy in unsuccessful cases. The surgery cure rate is only one half in the case of macroadenomas and it takes years before radiotherapy normalizes GH and IGF-I levels. In the interim, medical therapy is necessary. Second-generation dopamine agonists (cabergoline) are successful in about one third of patients, especially in those with lower basal IGF-I levels and with adenomas co-secreting prolactin. Somatostatin analogues octreotide and lanreotide are the gold standard of medical treatment - both are available in a form applicable as once-monthly injections. They successfully control disease activity in the majority of patients and induce tumour shrinkage in part of adenomas. Surgical debunking of macroadenomas improves the results of therapy with somatostatin analogues and it is not necessary to discontinue this thera...
The authors describe a female patient with large parathyroid gland adenoma presenting with clinic... more The authors describe a female patient with large parathyroid gland adenoma presenting with clinical symptoms of primary hyperparathyroidism and severe hypercalcaemia. Before planned surgical treatment the patient spontaneously developed clinical symptoms of tetany. Hypocalcaemia was confirmed by laboratory test. The reason turned out to be spontaneous necrosis of the parathyroid adenoma, resulting in remission of hyperparathyroidism. After stabilization of calcium levels, the necrotic adenoma was removed and histopathological examination revealed necrotic adenoma with only occasional vital adenoma cells. During the next follow-up the patient was without any subjective complaints and her state was stable. This phenomenon, yet described in the literature in past, belongs to unusual findings.
Human thyroid peroxidase (hTPO) is a membrane protein with a key role in the thyroid hormones syn... more Human thyroid peroxidase (hTPO) is a membrane protein with a key role in the thyroid hormones synthesis. Loss of hTPO was described in malignant tumours of the thyroid gland. hTPO was tested as a marker of malignancy. Immunohistochemical study of hTPO in 321 thyroid lesions (45 malignant tumours, 72 benign tumours, 199 benign non-tumours lesions, and 5 normal thyroid glands) is presented. The sensitivity of hTPO in predicting malignancy in thyroid is 64%, and the specificity is 87%. Thus, hTPO is of limited value in the diagnosis of thyroid malignancy. The authors discuss the role of hTPO as a marker of differentiation.
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