Project proposal. Evaluating human health risk from low-dose and long-term exposure to polychlorinated biphenyls.
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Biomedical subjects
Publications and source records attributed to P Langer.
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Female patient (42 yr) suffered from autoimmune thyroiditis resulting in severe hypothyroidism. She was treated for several years by district physician with the dose of 150 microg L-thyroxine daily. Since the level of TSH was repeatedly very high and no improvement of clinical signs has been observed, she was referred to the Medical Faculty Hospital. Thyroid ultrasound showed remarkable diffuse hypoechogenicity, thyroid scintigraphy showed enlarged thyroid with low 99mTc uptake, TRH test was normal, thin needle biopsy supported autoimmune thyroiditis. X-ray examination showed normal sella turcica and no changes in the pituitary were observed with computer tomography. In spite of increasing the dose of peroral L-thyroxine to 300 microg/d and later to 500 microg/d the clinical status and TSH level did not improve. The patient was originally suspected from malabsorption of thyroxine. However, the test with a large single peroral dose (1000 microg) of L-thyroxine showed a rapid decrease of TSH level (from 126 to 75 mU/l) and increase of total T4 level (from 18 to 64 nmol/l) within 4 hr. Later the patient has been treated with intravenous L-thyroxine (500 microg every 3-4 days for 4 weeks) which resulted in the decrease of TSH level to 10 mU/l and increase of T4 level to 80-100 nmol/l. After that it was concluded that the problem is a poor compliance of the patient who apparently does not actually take the medication, although she always claimed that she is doing so. Referring to some similar cases described in the literature the case was classified as thyroxine pseudomalabsorption. In spite that this problem has been explained to her and her relatives, she refused to take any medication and is consistently neglecting all invitations to further examinations.
UNLABELLED: After 45 years of successful iodine prophylaxis a total of 6324 subject aged 7 to 70 years from East (72.0%), Central (16.2%) and West Slovakia (11.8%) were examined. The thyroid volume (ThV) by ultrasound was examined in a total of 6045 subjects. Serum level of thyrotropin (TSH) was estimated in 1919 (30.3%) and anti-thyroperoxidase antibodies (anti-TPO) in 2589 (40.9%) subjects. Iodine was estimated in 1983 (31.3%) spot urine samples. The median and 75th percentile of ThV were increasing (respectively) from 3.9 and 5.2 ml (10 yr), 8.2 and 10.2 ml (17 yr), 12.4 and 16.3 ml (31-40 yr) up to 14.1 and 19.9 ml (61-70 yr). The frequency of ultrasound hypoechogenicity as an early sign of autoimmune thyroiditis increased from 3.9% (28/709; 10 yr), 16.3% (66/403; 21-40 yr) and 30.3% (205/665; 41-60 yr) up to 51.0% (48/94; 61-70 yr). Positive anti-TPO level as an other sign of autoimmune thyroiditis was found in 1.6% (11/683; 7-13 yr), 7.3% (47/644; 17-30 yr) and 20.4% (257/1262; 31-70 yr). In the adults 19.0% (268/1409) positive anti-TPO were found. Among 1367 adults 6.2% (N = 85) of TSH levels were higher than 4.0 mU/l and 7.5% (N = 103) were lower than 0.2 mU/l. Among 1504 adults a total of 93 (6.1%) of nodules larger than 10 mm in diameter was found (14 in males and 75 in females). In this study the nature of nodules remained unidentified, since all subjects were referred to additional examinations. Malignant nodules were suspected in 3 females with high serum thyroglobulin level and in one additional female with occasionally found very large nodule. The estimation of urinary iodine showed a majority of values in optimal range (> 100-200 microg/l). CONCLUSIONS: Thyroid volume in about 75% examined subjects of all age groups may be considered as relatively small which is apparently due to 45 years of effective iodine prophylaxis. In spite of that the volume of remaining about 25% thyroids were apparently increased which may be presubambly explained by the effect of mainly genetic, but also environmental factors.
UNLABELLED: The authors compared the size of the thyroid gland, assessed by ultrasonographic examination of its volume and the functional state of the thyroid by examination of the serum level of TSH and anti-TPO antibodies in 492 pupils aged 10 and 13 years in two close agricultural areas. The areas differed above all as to the nitrate content of drinking water. In communities where the source of drinking water were private wells (nitrate area), as much as 68.1% of the water samples had a nitrate content > 50 mg/l and 46.4% samples > 100 mg/l. In communities where the source of drinking water was a water main with a known source (control area) the water samples did not exceed 50 mg/l (73.7% > 15 mg/l and 26.3% > 50 mg/l. RESULTS: Pupils from the nitrate area had a larger thyroid gland similarly as older pupils from the control area. A volume above 7 ml/m2 in the nitrate area was recorded in the group of 10-year olds in 25/99 (27.7%) and in the group of 13-year-old ones in 33/154 (21.4%), while in the control area it was in the 10-year-old ones 11/92 (11.9%) and in the 13-year-old ones 16/156 (10.2%, P < or = 0.01). In the nitrate area TSH > 5 mIU/l was recorded in 5.6% and higher anti-TPO antibodies in 2.6% pupils. In the control area the corresponding figure was 1.1% pupils, P < or = 0.01.
Esophagectomy for esophageal carcinoma is associated with significant morbidity. Long-term survival rates are usually poor. Common problems in the early postoperative period are pulmonary complications and leakage at the collar anastomosis causing local infection, sepsis and subsequent anastomotic strictures. There are only a few reports in the literature about benign ulcerations in the gastric tube after resection of the esophagus for carcinoma. We report a patient with a huge benign ulcer in the gastric tube penetrating into the right lung 9 years after esophagectomy for carcinoma. Several aspects of possible etiologic factors and different prophylactic approaches as well as therapeutic aspects are discussed.
We report the CT findings of a solitary fibrous tumor of the orbit. The radiologic features included relatively homogeneous contrast enhancement and smooth remodelling of the bones of the orbit, findings consistent with the benign nature of this relatively rare tumor.
The objective of this study was to answer the question whether thyroid volume in adolescent siblings of similar age and a life-long sufficient iodine intake is uniform. If different, it would indicate that genetic or environmental factors unrelated to iodine intake can influence thyroid growth. We measured thyroid volume by ultrasound in: (1) 251 sibling pairs (SP) and 19 sibling triads 10 to 18 years of age. The age range of each SP was less than 24 months and of each triad less than 42 months; (2) 28 monozygotic and 13 dizygotic sets of twins 7 to 18 years of age. The sibling pairs were retrospectively divided into 3 groups irrespective of age (thyroid volume as means+/-S.E. mL/m2). Group 1: 159 pairs with low thyroid volume in both siblings; mean thyroid volume of each pair less than 5.00 mL/m2 (3.96+/-0.05, median 4.08, range 2.07-4.98); group 2: 69 pairs with high thyroid volume in both siblings; mean thyroid volume greater than 5.00 mL/m2 (5.85+/-0.12, median 5.57, range 5.03-11.02); group 3: 23 pairs with low thyroid volume in 1 sibling (3.53+/-0.15, median 3.53, range 1.71-4.91) and high thyroid volume in another (7.36+/-0.23, median 7.18, range 5.96-10.30). The majority of triads, monozygotic, and dizygotic twins resembled group 1, a few resembled group 2, and only 3 triads and 1 set of dizygotic twins resembled group 3. Among monozygotic twins, there was no pair with a strikingly discordant thyroid volume and only 1 such pair was found among dizygotic twins. In monozygotic twins, the thyroid volume was almost identical (mean difference 0.34+/-0.06 mL/m2) and significantly less (p < 0.012) than in dizygotic twins (0.9+/-0.25 mL/m2). Among 502 children of 251 sibling pairs the frequency of high thyroid volume (>5.00 mL/m2) was greater in girls (103/279, 36.9%, p < 0.01) than in boys (49/223, 22.0%). The same was true for the frequency of hypoechogenicity (42/279 or 15.0% in girls vs. 12/223 or 5.4% in boys; p < 0.01). The frequency of hypoechogenicity in both sexes of the combined groups 2 and 3 (40/186, 21.5%) was higher (p < 0.001) than in group 1 (14/316, 4.4%). All siblings examined lived in a common household with their parents, eating the same daily meals at home and school. Our results suggest that the observed differences in thyroid volume of siblings were not related to iodine intake, but to other factors, eg, genetic and environmental. It is not clear whether the children with high thyroid volume and increased frequency of hypoechogenicity should be included into the recently recommended range of normal thyroid volume for adolescents.
We report a patient with massive facial sarcoidosis. While skin involvement is a common manifestation of sarcoidosis, it is unusual to see it in the dramatic form of cutaneous tumors with mutilation of the central face. There are few reports of tumoral cutaneous sarcoidosis like that of our patient.
Although the goitre seems to be well defined at least from clinical point of view, it is virtually impossible to find the precise definition of the opposite side of what should be the normal thyroid as concerns its size, histological structure and namely the level of growth stimulation by the external factors (such as TSH) and intrinsic tissue growth factors. Theoretically, the normal thyroid should be able to cover the requirements of the organism for the hormone in a reasonably large range without being stimulated to grow by any external or internal factors. So far, the search for normal thyroid has been conducted by several ways: 1. by post mortem thyroid weight, 2. by palpation, 3. by ultrasound. As based on post mortem thyroid weight, until the middle of this century a typical thyroid gland was considered to be about 20-25 g with the accepted upper normal size of 30 g, while more recent studies in iodine replete population have reported mean weights of about 10 g and an upper normal size 20 g. According to several classifications for thyroid palpation the unpalpable thyroid should be allotted to the Grade 0 which is defined as "normal gland", "no goiter at all", "absence of goiter" etc. The first recommendation of normal thyroid volume for children and adolescents as estimated by ultrasound has been developed by Gutekunst and Teichert (1994). However, this was later challenged by the findings of considerable number of thyroid volumes which were higher than the upper limit of that recommendation as found in the countries with satisfactory values of urinary iodine (Delange et al. 1997). Nevertheless, recently it appeared that about 10-15 percent of adolescent thyroids show increased thyroid growth rate which significantly differs from the majority and which might be related to different tuning of molecular growth mechanism presumably of genetic origin (Tajtakova et al. 1998; Langer et al., in press). From, this follows that a certain number of enlarged thyroids apparently should not be included into a normal range.
OBJECTIVE: To estimate the excretion of triiodothyronine by bile in groups of rats infused with glucose, arginine or glucose combined with various doses of insulin. MATERIALS AND METHODS: Groups of about eight male Wistar Olac rats were anesthetized by pentobarbital and thin polyethylene tubings were inserted into bile duct and femoral vein. The bile was collected into pre-weighed glass vials which were changed every hour. The first one hour interval was considered as control and during the second hour the following i.v. infusions were applied: 1. 2.4 ml 30 % glucose; 2. arginine (80 mg/2. 4 ml saline); 3. 2.4 ml 30 % glucose containing 62.5, 125, 250 or 500 mU insulin. In some groups cycloheximide (2.5 mg/kg) or somatostatin (20 microg/kg) were used. The aliquots of bile were treated with beta-glucuronidase/arylsulfatase and the concentration of total (i.e. conjugated plus unconjugated) triiodothyronine was estimated by specific inhouse radioimmunoassay. The results were expressed as ng/hr and the volume of bile was estimated by weighing the previously tared collection vials. RESULTS: Significant increase of biliary T3 excretion was found during the 60 min infusion of glucose or arginine. However, in fed rats such increase did not continue after the termination of infusion, while in fasted rats the increase was observed still for next 60 min after the infusion. The attempts to further stimulate the excretion of T3 by the addition of small insulin doses (62.5, 125, 250 and 500 mU) to the infused glucose showed inversed effect: by such intervention the increase of T3 was blunted by higher doses, while at lower doses unsignificant increase appeared. The increase of biliary T3 excretion was also blunted by cycloheximide (translation inhibitor) and somatostatin (insulin release inhibitor) both in normal fed and 24 hr fasted rats. CONCLUSIONS: Short-term i.v. infusion of glucose and arginine resulted in immediate and transient increase of biliary T3 excretion which was inhibited by both the cycloheximide and somatostatin. Taken together with our previous findings, this supports the view on rapid fluctuation of hepatic iodothyronine metabolism as related to preprandial (prevailing effect of gluconeogenetic hormones resulting in preferential formation of rT3) and postprandial period (predominant effect of insulin resulting in preferential formation of T3).
Thyroid gland ultrasonography is recommended in patients with nonspecific clinical symptoms such as fatigue, weight gain, dry skin, amnesic symptoms, depression, bradycardia, abnormal myocardial contractility, increased diastolic pressure, hypercholesterolemia, menstrual abnormalities, infertility, fibrocystic breast disease, anxiety, insomnia, tachycardia, paroxysmal atrial fibrillation and osteoporosis. Subclinical hypothyroidism or hyperthyroidism can cause any of the above mentioned symptoms. Diffusely decreased, decreased and inhomogenous thyroid gland echogenicity requires laboratory examination. Thyroid gland ultrasonography is recommended also in patients with type I. diabetes mellitus and vitiligo because of increased incidence of thyroid disorders in these patients. Clinical observation of patients treated with Lithium, Amiodaron or Interferon is also recommended. (Tab. 2, Fig. 6, Ref. 18.)
BACKGROUND: Large adenomas and low-risk rectal carcinomas (T1) that are localized distal of the pelvic peritoneal reflection (PPR) are treated by transanal excision. However, the location of the PPR varies widely and cannot be detected reliably by preoperative methods. Therefore, we evaluated the value of endorectal ultrasound (EUS) for the prediction of an intraperitoneal location of rectal tumors. METHODS: Fourteen patients with rectal tumors measuring </=15 cm from the anal verge were examined by EUS. If peristalsis beyond the rectal wall or any intraperitoneal fluid was seen at the proximal tumor edge, the lesion was classified as localized above or in the level of the PPR. During the operation, the surgeon determined whether the upper end of the tumor reached the PPR. RESULTS: In each of our 14 patients, the prediction by EUS was correct. In two patients, a small rectal tumor was excised with an electric sling during rectoscopy, but the polyp bases were not free of dysplastic epithelial tissue. The point where these two polyps were removed could be visualized by endoscopy but not by EUS. Once the relevant area was marked with a titanic endoclip, EUS was able to predict the resection place in relation to the PPR in these two patients as well. CONCLUSIONS: Although this knowledge would be very important for the therapeutic strategy of small rectal tumors, it is impossible to determine the location of a rectal tumor with regard to the PPR either clinically or by endoscopy. EUS provides this information with high reliability. Thus, we recommend EUS as the method of choice for predicting the location of the PPR.
OBJECTIVE: To evaluate whether small iodine supplements decrease the incidence of adolescent thyroid hypertrophy in an iodine-sufficient population or whether such thyroid enlargement should be considered an inevitable physiological phenomenon. DESIGN: Beginning in September 1991 (after an initial examination in September 1990), 54 11-year-old children in Bardejov, Slovakia were given small iodine supplements (Thyrojod depot tablets containing 1530 microg iodide) every 2 weeks for 2 years followed by once weekly for 2 years. A second group of 63 children served as controls. In June 1995, there were still 52 treated and 60 control children in the study and these were examined; 44 treated and 48 control children remained in the study until June 1997. METHODS: In 1990, 1993, 1995, 1996 and 1997 the thyroid volume (ThV) was measured by ultrasound. Serum levels of TSH, thyroglobulin, total and free thyroxine and tri-iodothyronine and anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) and anti-TSH receptor (TSR) antibodies were estimated in 1990 and 1994, while only TSH, and anti-TPO and anti-TSR antibodies were measured in 1997. RESULTS: There was no difference between the groups at any interval in the serum levels of the hormones measured. Marginally increased TSH was found in two treated and two control children. Anti-TSR antibodies were negative in all children, while anti-TPO and anti-TG antibodies were found in one treated and four control children. At the age of 10 years (1990), 84% of all ThVs were less than 4 ml, indicating a previous life-long sufficient iodine intake. After the treatment was completed (June 1995), a significant difference in ThV (P < 0.04) was found between the whole treated (5.78 +/- 0.19 ml) and the whole control group (6.56 +/- 0.30 ml). However, there was already a marked difference in the 75th percentile (6.4 ml in treated vs 8.5 ml in controls) due to more rapid thyroid growth in certain children of the control group (ThV > 7.0 ml in 6/52 treated children vs 24/60 controls; P < 0.01). Since such differences were much higher in 1997, the children in each group whose ThV was in the range of the upper 25% in 1997 were retrospectively evaluated as arbitrary separate subgroups in all the time intervals and compared with the remaining 75% of children who showed moderate thyroid growth rate. Two years after the termination of treatment (June 1997), excessive thyroid growth continued in the upper quarter of 12 controls with the highest ThV (13.60 +/- 0.40 ml or 7.60 +/- 0.29 ml/m2; 12/12 with ThV > 11.0 ml), and a similar subgroup now also appeared in 11 previously treated children (10.79 +/- 0.51 ml or 6.19 +/- 0.30 ml/m2; 5/11 with ThV > 11.0 ml). At the same time, ThV in the remaining 75% of both control (8.12 +/- 0.38 ml or 4.82 +/- 0.17 ml/m2; 3/36 with ThV > 11.0 ml) and treated (7.20 +/- 0.30 ml or 4.39 +/- 0.17 ml/m2; 0/33 with ThV > 11.0 ml) children was significantly less (P < 0.01 to P < 0.001) than that in the appropriate rapidly growing subgroups. During the whole observation period (1990-1997), no difference was found between treated and control subgroups with moderate thyroid growth. CONCLUSIONS: Since iodine intake in Slovakia has been adequate for decades and sporadic iodine deficiency is highly unlikely, the observed excessive thyroid growth in certain adolescents may result from causes other than simple iodine deficiency (e.g. hereditary), which are nevertheless ameliorated by small iodine supplements. The question remains whether such a subgroup with rapidly growing thyroids should be included in the range of normal thyroid volumes in adolescents.
OBJECTIVE: To evaluate whether long-term exposure to heavy environmental pollution with polychlorinated biphenyls (PCBs) could result in impairment of thyroid status as evaluated by an epidemiological field survey. METHODS: Thyroid volume (ThV) was measured by ultrasound in 238 employees of a factory (EMP) which previously produced PCBs and 454 adolescents from the surrounding area polluted by PCBs. Controls (C) were 572 adults and 965 adolescents from much less polluted areas. In the 238 EMP and various numbers (shown in parentheses) of adult C the levels of thyroid-stimulating hormone (TSH) (n = 498), thyroxine (n = 498), thyroglobulin (n = 278) and thyroid antibodies (anti-peroxidase (TPO Ab), n= 517; anti-thyroglobulin (Tg Ab), n=455; anti-TSH receptor (TSHR Ab), n=238) were estimated in serum, while only TSH and TPO Ab were measured in 269 and 171 adolescents from polluted and control areas respectively. In several subjects in whom thyroid disease was suspected, total tri-iodothyronine or free thyroxine and tri-iodothyronine were measured. In a total of 362 adults and adolescents the urinary iodine was estimated. RESULTS: Using the Mann-Whitney test, ThV in EMP (mean+/-S.E. = 18.85+/-0.69 ml, median= 17.3 ml, upper quartile=22.9 ml, n=238) was significantly higher (P< 0.001) than that in C (13.47+/-0.48 ml, 11.5 ml, 15.3 ml, n = 486 respectively). Similarly, ThV in adolescents from the polluted area (9.37+/-0.17 ml, 8.9 ml, 11.0 ml, n = 454 respectively) was significantly higher (P< 0.001) than that in C (8.07+/-0.10 ml, 7.6 ml, 9.6 ml, n = 965 respectively). In adults, a significantly increased prevalence of TPO Ab (P<0.05) was found (using the chi-square test) in EMP women of all ages (54/190) vs C women (70/282), in EMP women aged 31-50 years (40/117 vs 70/282 respectively) and those aged 41- 50 years (28/77 vs 54/215 respectively). Compared with C, there was also a higher prevalence of Tg Ab in EMP women aged 31-60 years (36/169 vs 50/342 respectively) and of TSHR Ab (P< 0.001) in the group of EMP men and women (25/238) vs sex- and age-matched C (6/238). No difference between EMP and C was found in the level of thyroxine (mean+/-S.D = 116.1+/-31.2 nmol/l, n = 238 vs 112.2+/-37.0 nmol/l, n = 460 respectively), TSH in the range 0.1-4.5 mU/l(1.56+/-0.86 mUl/l, n = 219 vs 1.51+/-0.84 mU/l, n = 460 respectively), prevalence of TSH >4.5 (14/238 vs 28/498 respectively) and <0.1 mU/l(5/238 vs 10/498 respectively). The prevalence of individuals without any defined clinical or laboratory signs of thyroid disorders among EMP who had worked in the factory for 21-35 years (43/128, 33.6%) was significantly lower than that in twice as many matched C (118/256, 46.1%, P< 0.025) or in EMP who had worked for only 11-20 years (36/73, 49.3%, P< 0.05). In adolescents, no difference was found in the prevalence of TPO Ab or TSH >4.5 mU/l between the polluted (17/269, 6.3%, and 2/243, 0.8% respectively) and C areas (15/171, 8.5% and 4/140, 2.8% respectively). The median values of urinary iodine were in the optimal range (microg per dl/number of cases) and about the same in polluted (12.6/90 and 11.4/55) and C areas (14.1/80, 13.2/82 and 13.4/55). CONCLUSIONS: Since iodine intake in Slovakia is considered sufficient as a result of 45 years of well-monitored iodine prophylaxis, the increased ThVand prevalence of thyroid disorders in the polluted areas presumably results from long-term exposure to toxic substances rather than from a difference in life-long iodine intake. The increased prevalence of some thyroid antibodies may be related to the known immunomodulatory effects of PCBs.
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The effect of feeding Wistar rats with high-sucrose (63 wt% of sucrose, HS) or high-fat (30 wt% of fat, HF) diets for two weeks on serum selenium concentration and type I iodothyronine 5'-deiodinase (5'-DI) activity in liver was investigated. No significant differences in serum selenium concentration (as determined by graphite-furnace atomic absorption spectrometry) were found among the groups of rats fed basal, HS, or HF diets. A significant reduction of the 5'-DI activity (p < 0.005-0.05) was found in groups of rats fed either HS or HF diet in comparison with rats fed B diet. In conclusion, it is suggested that decreased 5'-DI activity in HS or HF diet-induced insulin resistance is not due to selenium status, but it may involve other dietary-related factors.
The fatty acid (FA) compositions of liver and skeletal muscle structural lipids, overall phospholipids and phosphatidylcholine, and triglycerides (TG) were determined in the hereditary hypertriglyceridemic (HTG) rat, a nonobese animal model of the insulin resistance syndrome. Four groups of HTG rats and four groups of control animals were fed equal-energy diets for two weeks: basal (B), high-sucrose (HS), or fish oil-supplemented basal (BFO) or high-sucrose (HSFO) diets. In the liver of HTG rats, a decrease of n-6 long-chain polyunsaturated FA (PUFA), especially in 20:4n-6, in comparison with controls was found. Moreover, a concomitant accumulation of 18:2n-6 in structural lipids was observed. These differences were more pronounced in liver than in skeletal muscle. HS feeding raised the proportion of 18:1n-9 and decreased 18:2n-6 in lipid fractions. In both tissues and in both strains, the amounts of long-chain n-3 PUFA, as well as the level of total C20-22 PUFA, went up after fish oil feeding. However, the effects were somewhat less pronounced in the HTG rats. The increase in n-3 PUFA occurred mainly at the expense of reduced levels of 18:2n-6 in structural lipids and of 18:1n-9 in triglycerides. These changes were associated, in companion studies reported in this volume, with improved insulin action in HTG rats. In conclusion, the FA composition in lipid subclasses of HTG rats differs significantly from the controls mainly in liver structural lipids, suggesting the impairment of PUFA desaturation. Dietary change effected a similar modulation of FA profile across both strains, with fish oil increasing the levels of long-chain PUFA toward control values in the NTG rats. The HTG rat thus provides an interesting animal model for the study of impaired fatty acid metabolism.
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