Search PubMed⌕ Search

Biomedical subjects

A Lewiński

Publications and source records attributed to A Lewiński.

At least 19 recordsLinked to original sources

Evaluation of the diagnostic value of the first thyroglobulin determination in detecting metastases after differentiated thyroid carcinoma surgery.

AIM: Evaluation of the diagnostic value of the first thyroglobulin (Tg) level measurement, performed after thyroidectomy, before another treatment, as an early marker of either metastases or local recurrence of differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: Data of 178 patients (160 women, 18 men, 14-79 years) with DTC and without known interference in Tg assay were evaluated retrospectively. In all patients, neck radioiodine uptake (Tup (24)), thyroid remnants volume (V), TSH and Tg were measured. The Tg/V and Tg/Tup (24) ratios were calculated to correct Tg concentration with regard to V and Tup (24). Six months after initial evaluation and routine therapy all patients underwent control examinations under endogenous TSH stimulation. RESULTS: During follow-up metastases or local recurrence were found in 32 patients. The groups of patients with no diagnosed metastases (M0) and with detected metastases (M1), did not differ with regard to V, serum TSH or Tup (24); difference between the two groups was found in Tg concentration (4.3 ng/ml VS 97.4 ng/ml; p=0.000001). The ratios of Tg/Tup (24) (p=0.000000) and Tg/V (p=0.004) were lower in the group M0 than M1. The areas under receiver operating characteristic curves (ROC) for Tg concentrations, Tg/Tup (24), and Tg/V ratios were 0.773 (95% CI - 0.655-0.892), 0.817 (0.709-0.925) and 0.712 (0.541-0.884), respectively. CONCLUSIONS: Both the absolute Tg concentration and Tg/V and Tg/Tup (24) ratios, determined after thyroidectomy but before another treatment in patients with metastases of DTC, diagnosed within 6 months after (131)I administration, are higher than those in patients without such metastases. This indicates that the mentioned parameters may be applied as early markers of either local recurrence or metastases of DTC. The highest discriminative value demonstrates Tg/Tup (24) ratio, Tg concentration has a lower value and Tg/V ratio has the lowest one.

Adolescent↗

A novel mutation in the thyrotropin (thyroid-stimulating hormone) receptor gene in a case of congenital hypothyroidism.

Congenital hypothyroidism (CH) occurs approximately with a frequency of 1 in 3000-4000 births, being a disease caused by defects in thyroid hormone synthesis associated either with goiter presence or with agenesis or ectopy of the thyroid gland. A study of some familial cases has allowed identification of mutations in several known genes, including that encode the thyroid-stimulating hormone receptor (TSHR). We report a familial case of CH that transmitted as a recessive trait and caused by a novel homozygous nonsense mutation in TSHR with an initial diagnosis of thyroid agenesis hypoplasia. Genomic DNA was obtained from two siblings and their parents; TSHR was amplified using pairs of overlapping exonic primers; and polymerase chain reaction products were automatically sequenced. The propositus was homozygous (genotype: M/M) for a novel C to G transversion (1431C>G), producing a nonsense mutation, Y444X, in the first intracellular loop of TSHR, rendering a truncated receptor. Thus, the observed unresponsiveness to TSHR may be due to absent insertion of the truncated receptor into the cell membrane (if it gets translated at all) or the truncation may lead to nonsense-mediated mRNA degradation (its unresponsive to TSH). Both parents were heterozygous (wWt/M) and unrelated, as known from family history. The other daughter was homozygous for both wild-type alleles (wWt/wWt).

Base Sequence↗

Diabetes screening after gestational diabetes mellitus: poor performance of fasting plasma glucose.

Gestational diabetes mellitus (GDM) is an established risk factor for the development of overt diabetes. Since the change in diagnostic criteria for diabetes in 1997, it is unclear whether there should be any preference for fasting or post-glucose challenge blood glucose in diagnosing diabetes after GDM. The study aimed at assessing the usefulness of both diagnostic methods in women after GDM. The study enrolled 193 women with previous GDM. Women who did not have a current diagnosis of diabetes were screened for impaired fasting glucose (IFG) and for glucose intolerance with an oral 75-g glucose tolerance test. A total of 45 (23.3%) subjects declared to be already diabetic. Of the 148 non-diabetic subjects, 141 (95.3%) had normal fasting plasma glucose, whereas four (2.8%) had IFG (i.e. FPG> or =6.1 and <7.0 mmol/l) and 3 (2.5%) had FPG> or =7.0 mmol/l. Upon OGTT, among the 141 subjects with normal FPG, 6 (4.3%) were diagnosed with diabetes and 23 (16.3%) with impaired glucose tolerance (IGT); the remaining 112 (79.5%) had normal glucose tolerance. Three out of four subjects with IFG had IGT. The sensitivities of fasting criteria for diagnosis of diabetes and IFG/IGT were 14.3% (95% CI, 8.0%-37.2%) and 17.1% (95% CI, 8.6%-19.8%), respectively. The specificities were 98.6% (95% CI, 97.9%-99.7%) and 99.1% (95% CI, 96.5%-100%), respectively. The kappa for diabetes diagnosis was 0.177 (95% CI, 0.018-0.507). For women with previous GDM, the sensitivity of the new criteria based upon fasting plasma glucose is unacceptably low. In addition, the two sets of criteria are not interchangeable. Therefore, we suggest full glucose tolerance diagnostic procedures in women after GDM, including assessment of post-glucose challenge values.

Blood Glucose↗

Multiparameter analysis of AgNOR in thyroid lesions: comparison with PCNA expression.

The aim of the study was to examine numerous features of argyrophilic proteins related to nucleolar organizer regions (AgNORs) in thyroid tumors, relate them to PCNA expression and evaluate which of these features might be useful in the diagnosis of thyroid lesions. Paraffin sections of 100 thyroid tumors were silver-stained and divided into 9 groups: nodular goiter (NG), simple adenoma (SA), microfollicular adenoma (MFA), follicular carcinoma (FC), follicular variant of papillary carcinoma (PC-F), classical variant of papillary carcinoma (PC-C), Hürthle cell adenoma (HA), Hürthle cell carcinoma (HC), and anaplastic carcinoma (AC). The slides were analyzed with the computerized system for image analysis. A weak correlation was found between PCNA expression and AgNOR size. AC differed significantly from all other examined groups in many features of AgNOR dots. Hürthle cell neoplasms were characterized by the presence of a usually single and relatively large dot. With respect to diagnosing follicular lesions, we found that the evaluation of the total area of dots in the nucleus seemed to be the most useful for discrimination: the assumption of 4.9 micro m2, as a cut-off value, allowed a correct classification of 77% of FC cases. Computer-aided morphometric analysis of AgNORs may be useful in the diagnostics of thyroid lesions.

Adenocarcinoma, Follicular↗

Fine needle aspiration cytology in non-neoplastic non-toxic recurrent nodular goitre.

The aim of the study was to examine whether evaluation of anisokaryosis is helpful in the cytological diagnosis of focal lesions in non-toxic recurrent goitre (NRG) after thyroidectomy for non-malignant goitre. Karyometric analysis was performed in routine cytological smears obtained from 80 females: 40 with focal lesions in non-toxic primary goitre (NPG) and 40 with NRG (postoperative histopathological examination revealed nodular goitre in both groups in all cases). We found that the level of anisokaryosis was significantly (P<0.005) higher in NRG than in NPG. There were no significant differences between the two lesions, in cellular composition or thyroid follicular cell arrangement. Thus, isolated anisokaryosis, a feature of malignancy in patients without a prior thyroidectomy, has limited diagnostic value in recurrent goitre.

Adult↗

Iodine-induced hyperthyroidism--an epidemiological survey several years after institution of iodine prophylaxis in Poland.

In 1997, the obligatory model of iodine prophylaxis was introduced in Poland in order to correct the existing status of mild and/or moderate iodine deficiency. In order to monitor possible side-effects of increased iodine supply, studies on iodine-induced hyperthyroidism were initiated by establishing several regional registers of hyperthyroidism. In the present paper, the results of a two-year monitoring (2000-2001) have been summarized. There are no epidemiological data on hyperthyroidism prior to starting the iodine prophylaxis, but the obtained current data are comparable to observations in other countries, made after iodine supplementation. The incidence of iodine-induced hyperthyroidism did not exceed the acceptable level, thus confirming--together with previous observations on the effectiveness of iodine prophylaxis--the adequacy of applied dose of KI (30 microg/kg NaCl), used for salt iodization in Poland.

Adult↗

Carcinogen-induced, free radical-mediated reduction in microsomal membrane fluidity: reversal by indole-3-propionic acid.

Chromium (Cr) is a well established carcinogen, with Cr(III) accounting for much of the intracellular oxidative damage that this transition metal induces. Indole-3-propionic acid (IPA), a melatonin-related molecule, is a reported antioxidant and free radical scavenger. Concentration (1, 10, 100, 500, or 1000 microM) and time (15, 30, 45, 60, or 90 min)-dependent effects of Cr(III) in the presence of H2O2 (0.5 mM), as well as the protective effect of IPA on Cr(III)-induced alterations in membrane fluidity (the inverse of membrane rigidity), as an index of membrane damage, were estimated by fluorescence spectroscopy. Cr(III), in a concentration- and a time-dependent manner, decreased membrane fluidity, with marked effects at a concentration of 500 microM and 60 min of incubation. IPA (5, 3, or 1 mM) prevented the Cr(III)-induced decrease in membrane fluidity. It is concluded that the carcinogen Cr(III), in the presence of H202, generates free radicals, which decrease membrane fluidity in rat microsomal membranes. Membrane alterations are pharmacologically prevented by the antioxidant IPA.

Animals↗

Correlation between PCNA expression and AgNOR dots in pituitary adenomas.

Nucleolar organizer regions are segments of DNA associated with argyrophilic proteins (AgNORs). Our previous findings showed that the number, the area, and the intranuclear localization of AgNOR dots differ according to tumor aggressiveness and to the hormone-immunopositivity of pituitary adenomas. Proliferating cell nuclear antigen (PCNA) is a nuclear protein, whose expression is correlated with cell proliferation. The aim of the present paper was to examine PCNA-labeling indexes in pituitary adenomas and to correlate them with AgNOR dots in various immunohistochemical types of the tumors. Histological slides from 32 pituitary tumors and one normal pituitary were silver-stained and analyzed with a computerized system for microscopic image analysis. We found that the percentage of PCNA-positive cells did not differ significantly among examined groups of monohormonal adenomas. However, tumors immunopositive for alpha-subunit (alpha-SU) showed a significantly higher (p < 0.05) PCNA index than adenomas immunonegative for that unit. PCNA index in recurrent tumors was significantly higher than in primary adenomas. There was a moderate positive correlation between the PCNA index and the mean area of AgNOR dots and a similar correlation between the PCNA index and the area of the biggest dot in the nucleus. The obtained results reveal that the PCNA indexes and estimated parameters of AgNOR dots differ according to tumor aggressiveness.

Adenoma↗

Indole-3-propionic acid, a melatonin-related molecule, protects hepatic microsomal membranes from iron-induced oxidative damage: relevance to cancer reduction.

Excessive free iron and the associated oxidative damage are commonly related to carcinogenesis. Among the antioxidants known to protect against iron-induced oxidative abuse and carcinogenesis, melatonin and other indole compounds recently have received considerable attention. Indole-3-propionic acid (IPA), a deamination product of tryptophan, with a structure similar to that of melatonin, is present in biological fluids and is an effective free radical scavenger. The aim of the study was to examine the effect of IPA on experimentally induced oxidative changes in rat hepatic microsomal membranes. Microsomes were preincubated in presence of IPA (10, 3, 2, 1, 0.3, 0.1, 0.01 or 0.001 mM) and, then, incubated with FeCl(3) (0.2 mM), ADP (1.7 mM) and NADPH (0.2 mM) to induce oxidative damage. Alterations in membrane fluidity (the inverse of membrane rigidity) were estimated by fluorescence spectroscopy and lipid peroxidation by measuring concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA). IPA, when used in concentrations of 10, 3 or 2 mM, increased membrane fluidity, although at these concentrations it did not influence lipid peroxidation significantly. The decrease in membrane fluidity due to Fe(3+) was completely prevented by preincubation in the presence of IPA at concentrations of 10, 3, 2 or 1 mM. The enhanced lipid peroxidation due to Fe(3+) was prevented by IPA only at the highest concentration (10 mM). It is concluded that Fe(3+)-induced rigidity and, to a lesser extent, lipid peroxidation in microsomal membranes may be reduced by IPA. However, IPA in high concentrations increase membrane fluidity. Besides melatonin, IPA may be used as a pharmacological agent to protect against iron-induced oxidative damage to membranes and, potentially, against carcinogenesis.

Adenosine Diphosphate↗

[Current views on diagnostic standards and treatments with L-thyroxine of single non-toxic thyroid nodules or multinodular non-toxic goiter].

The present opinions on the therapy with L-thyroxine (L-T4) of single non-toxic thyroid nodules, as well as of multinodular non-toxic goitre are rather divergent. This treatment is based on the suppression of TSH secretion from the pituitary. There are no doubts that FNAB performance is the first and--at the same time--the most significant diagnostic procedure in the case of thyroid structural lesions (nodules, goitre, thyroiditis). FNAB performance should--by all means--precede the beginning of L-T4 application for the treatment of thyroid nodules. The simplicity, clearness and high efficacy, with comparable results in each case, are the core of good diagnostic algorithm. Unfortunately, non all diagnostic algorithms concerning thyroid nodules and multinodular goiter, fulfill these important criteria.

Biopsy, Needle↗

[Prognostic significance of selected oncogene and suppressor gene expression in follicular thyroid carcinoma].

Oncogene and suppressor gene expression (cyclin D, p21WAF1, nm23-H1, Rb1, p16INK4A, and p53) was evaluated in 23 follicular thyroid carcinomas diagnosed in 20 women and 3 men operated or reoperated in Institute of Oncology in Gliwice in years 1992-1999. Positive reaction with p16INK4A, Rb1 and cyclin D1 antibodies was observed in all tumors, with nm23-H1 in 22 cases. The presence of p21WAF1 was stated in 8 cases (34.8%) and p53 in 7 cases (30.4%). A simultaneous presence of expression of p53 and lack of expression of p21WAF1 was stated three times and in two cases were accompanied by distant metastases. This pattern of expression was only rarely observed in minimally invasive follicular cancer. The prognostic significance of simultaneous immunohistochemical analysis of p53 and p21WAF1 in follicular thyroid carcinoma is suggested and has to be proved in further studies.

Adenocarcinoma, Follicular↗

Increased plasma concentration of epidermal growth factor in female patients with non-toxic nodular goitre.

OBJECTIVE: Epidermal growth factor (EGF) is believed to be one of the most potent growth factors for the thyroid gland. DESIGN AND METHODS: We tested plasma EGF concentrations (radioreceptor method) in patients with non-toxic nodular goitre (NNG). Blood samples from patients with NNG were collected on the day before the surgery, during subtotal thyroidectomy (sTx)--from peripheral and thyroid veins, on the 3rd day after sTx, 3 months after sTx, and 9 months after the surgery. RESULTS: Before the operation, the mean plasma EGF concentration in 50 women with NNG was significantly higher (1.16 +/- 0.69 ng/ml; mean +/- S.E.) than that in 32 control female patients subjected subsequently to other (non-thyroid) operations (0.41 +/- 0.27 ng/ml; P < 0.001), and that in 20 healthy women (0.35 +/- 0.11 ng/ml; P < 0.001), both of which groups were without goitre or had a small non-toxic diffuse goitre. The surgical treatment of NNG resulted in a significant reduction in plasma EGF 3 months after sTx (0.56 +/- 0.22 ng/ml). A further slight decrease was observed 9 months after sTx (0.44 +/- 0.14 ng/ml). CONCLUSIONS: Our observations confirm the assumption that EGF may participate in the process of goitre formation in human subjects. However, the source of EGF involved in this process remains unclear. Some findings could suggest that plasma EGF, which was increased in patients with NNG, may be of non-thyroid origin; however, the majority of our observations strongly stress the significance of an intact thyroid in the preservation of an unchanged EGF value, suggesting a role of locally produced EGF in the pathogenesis of NNG.

Adult↗

Usefulness of computer-aided karyometric examination in preoperative differentiation of Hürthle cell lesions.

We have previously reported that there is a significant difference in the mean size of thyrocyte nuclei among patients with nodular goiter, follicular adenoma, and follicular carcinoma. In the present study, we have examined karyometric parameters of Hürthle cells in smears collected from 41 patients with Hürthle cells adenomas, Hürthle cells carcinomas, nodular goiter, and lymphocytic thyroiditis. The karyometric evaluation was performed with the image analysis computer system-Karyometry Manager 1.2. We measured the mean volume, the mean intersection area, and the mean perimeter of 100 nuclei in each routine smear. We found that the sizes of Hürthle cell nuclei could be arranged in the ascending order from the nodular goiter, through lymphocytic thyroiditis to Hürthle cell neoplasms, but those differences did not reach a border of statistical significance.

Adenoma, Oxyphilic↗

Multifarious system for quantitative analysis of histologic compartments.

A system is presented for measuring relative volumes of histologic compartments in microscopic slides. The computer program for that system was written by us as an MS windows 3.x application. The applied method of measurements, based on the "point-counting" technique, requires the recognition of the compartments, corresponding to the selected points of an image. The neural network was employed to facilitate the process of classification of the examined points. Nine descriptors of an image were selected as an input to the network (a pattern). Error-free compartment recognition was not always achieved because of some overlapping of the pattern classes. Nevertheless, the semi-automation of the assignment of the examined points to histologic compartments makes the measurements less laborious and time-consuming.

Animals↗

[The role of genetic factors in the pathogenesis of thyroid neoplasms].

This paper summarizes the current knowledge on the role of genetic factors in the development of thyroid neoplasms. The introduction of the methods and concepts of molecular genetics (as, e.g. recombinant DNA technology) have elucidated etiopathogenesis of the majority of thyroid tumours and, in the future, can make the diagnosis easier. Mutations of genes involved in the control of cellular growth and/or differentiation (ras, c-myc, RET, met) affect the development of thyroid neoplasms. Loss of heterozygosity (LOH) may suggest the presence of tumor suppressor genes and has been reported in thyroid follicular carcinomas. Activation of tyrosine kinase, whether by specific oncogene amplification or by rearrangement, appears to be highly specific for the transformation of thyroid follicular cells into papillary tumours. Cytogenetic studies have shown frequent clonal abnormalities in thyroid follicular adenomas and carcinomas.

Adenoma↗

[Immunopathology of Graves'-Basedow disease].

The pathogenesis Graves' disease, an autoimmune disorder, is not fully understood. Immune disturbances, genetic predisposition and environmental factors, affecting thyroid gland, appear to play the main role in contribution and development of the disease. Autoreactive T lymphocyte infiltrates in the thyroid gland and/or in the retroorbital tissues and autoantibodies to TSH receptor detected in almost all of the patients, have been considered to be responsible for hyperthyroidism, ophthalmopathy, pretibial dermopathy and goiter. In this review, we describe some recent reports on the pathophysiological and immunological aspects of the thyroidal and extrathyroidal manifestations of the Graves' disease.

Autoimmune Diseases↗

Karyometric analysis in the cytologic diagnosis of thyroid lesions.

OBJECTIVE: To assess the possible role of karyometry in improving the diagnostic value of fine needle aspiration biopsy (FNAB) of the thyroid. STUDY DESIGN: Thyrocyte nuclei were evaluated in routine slides obtained from 229 patients. The cytologic specimens were divided into seven groups according to the results of corresponding postoperative histopathologic examinations. Karyometric measurements comprised assessment of nuclear volume intersection area and perimeter as well as level of anisokaryosis, evaluated as standard deviations of those parameters in single slides. The karyometric evaluation was performed with a computerized image analysis system. RESULTS: The size of thyrocyte nuclei increased from nontoxic nodular goiters through follicular adenomas, toxic nodular goiters treated with antithyroid drugs, lymphocytic thyroiditis, papillary and follicular carcinomas to anaplastic carcinomas. The observed differences between those groups were statistically significant, but there was marked overlapping. Our data indicate also that the age and sex of the patient influence the cytologic picture of nodular goiter. The evaluation of anisokaryosis increases the usefulness of karyometry in differentiating malignant neoplasms from benign lesions. CONCLUSION: Karyometric analysis increases the probability of a correct diagnosis with FNAB examination.

Adenocarcinoma, Follicular↗

Interactions between atrial natriuretic factor (ANF) and thyrotropin or somatostatin in their effects on thyroid growth processes; studies in vitro and ex vivo in vitro.

The goal of our present study has been to examine the effects of the atrial natriuretic factor (ANF) on the growth processes in rat thyroid lobes. In the initial in vitro experiment, thyroid lobes were preincubated with rat ANF (Sigma) for 30 min in RPMI 1640 medium with 3H-thymidine (2 microCi/ml), and later on 15% fetal calf serum (FCS), Hepes buffer and the remaining tested substances [TSH 20 mIU/ml, somatostatin (SS) 10(-7)M] were added. Preincubations with ANF were not conducted in the controls and in the group exposed to TSH alone. Incubations of all the examined groups (controls, TSH alone, ANF alone, ANF together with TSH or ANF together with SS) with 3H-thymidine were carried out for 4 hours. We obtained the following results: at none of the examined concentrations (10(-5)M, 10(-7)M, 10(-9)M), did ANF significantly affect the rate of 3H-thymidine incorporation in vitro. Neither did TSH alone nor ANF with TSH jointly significantly influence the process in question. However, we observed increased rates of the 3H-thymidine uptake, following the joint exposure of thyroid lobes to ANF (10(-7)M or 10(-9)M) and SS (10(-7)M), when compared to ANF alone. In the ex vivo in vitro experiment, direct intrathyroidal microinjections of ANF alone or jointly with TSH or SS, were carried out. Twenty four (24) hours after the microinjections, all the animals were sacrificed by decapitation, the thyroid lobes being collected and incubated for 4 hours with 3H-thymidine (2 microCi/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗