Search

Human ovarian preovulatory follicular fluids (FF) from 10 women were analysed for their complement contents. Functionally active complement was detected in all the fluids studied in amounts similar to those present in normal human serum. Pooled FF was challenged by seminal plasma in order to determine whether seminal plasma could activate FF complement, the pattern of such an activation and the possible consequences on the reproductive function. FF complement activation occurred during the incubation with seminal plasma with features including alternative pathway activation, factor B and C3 conversion and reduction in total haemolytic complement, as well as an inhibition by seminal plasma ofthe FF complement response to a new activating challenge. Possible consequences for fertilization, implantation of a fertilized ovum and local defence mechanisms against viruses and bacteria are discussed. [ABSTRACT FROM AUTHOR]

We recently described a solid phase immunoradiometric assay (IRMA) for anti-thyroglobulin and anti-thyroid microsomal antibodies. In the present study a similar IRMA for gastric parietal cell antibodies (PCA) has been developed. Samples to be tested are incubated within wells of polyvinyl microtitre plates coated with solubilized gastric microsomal antigen. After removal of unbound material, PCA is detected by adding purified 125I-anti-human IgG antibody. A good correlation was found with the results of PCA assays obtained by indirect immunofluorescence. In contrast, negative PCA by IRMA were consistently obtained in sera containing high titres of several other organ specific and non-organ specific autoantibodies. PCA determinations by IRMA were than carried out in a series of normal controls and patients with autoimmune or non-autoimmune thyroid disorders. Positive results were obtained in three of 70 (4.3%) apparently normal subjects, in 16 of 87 (18.4%) patients with Hashimoto's thyroiditis, in 10 of 48 (20.8%) with idiopathic myxoedema. in 25 of 95 (25.6%) with Graves' disease and in five of 64 (7.8%) with other non-autoimmune thyroid disorders. Preliminary results showed that quantitative measurements of PCA by IRMA could be performed using a serum containing high levels of PCA as standard reference. In conclusion, PCA may be easily and specifically detected using the same IRMA procedure previously developed for anti-thyroid antibodies. We therefore suggest that the present IRMA may be proposed as a general technique for the detection of different organ specific autoantibodies. [ABSTRACT FROM AUTHOR]

Parallel measurements of circulating anti-thyroid microsomal (anti-M) antibodies by radioassay and haemagglutinatinn were performed on subjects with or without thyroid disorders. Three quarters (75.4%) of control subjects had undetectable antibody levels (< 10 u/ml) by radioassay and only 3.1% had concentrations of &ges; 75 u/ml. Abnormally elevated levels (&ges; 75 u/ml) were found in most of the patients with Hashimoto's thyroiditis (94.1%) or idiopathic myxoedema (86.7%), in the majority (75.0%) of those with Graves' disease and only in a minority of those with other thyroid disorders. The percentage of positive sera by haemagglutination was verisimilar in all groups to that of abnormal values observed in the radioassay. Direct comparison of parallel tests on a total of 631 sera revealed a highly significant correlation (r = 0.91, P < 0.001) between the two methods, but elevated antibody titres by haemaegglutination were found in some sera with negative radioassays. All these sera were from a single patient with thyroid carcinoma associated with Hashimoto's thyroiditis and had elevated levels of anti-thyroglobulin (anti-Tg) antibodies. Evidence that such discrepancies were due to anti-Tg antibodies reacting with microsomal-bound Tg was provided by the demonstration that the haemagglutination produced by these sera could be completely inhibited by the addition of Tg. A similar inhibition was observed with two rabbit antisera to human Tg, but not with sera from patients with thyroid autoimmune disorders containing high levels of anti-microsomal anti-bodies. [ABSTRACT FROM AUTHOR]

Graves' orbitopathy (GO) is the main extrathyroidal manifestati on of Graves' disease (GD). Choice of treatment should be based on the assessment of clinical activity and seve rity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smo king, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments, and selenium (seleni um-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight-threatening GO, antithyroid drugs are preferred when managing Graves' hyperthyroidism. In moderate-to-severe and active GO i.v. gluco corticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safe ty profile, costs and reimbursement, drug availability, long-term effectiveness, and patient choice after extensive coun seling, a combination of i.v. methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 g of i.v. methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, h igher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplop ia. Second-line treatments for moderate-to-severe and active GO include (a) the second course of i.v. methylpredn isolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, (b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; (c) orbital radiotherapy combined with oral or i.v. glucocorticoids, (d) te protumumab; (e) rituximab and (f) tocilizumab. Sightthreatening GO is treated with several high single doses of i.v. methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint, and eyelid surgery) is indicated for inactive residual GO manifestations. [ABSTRACT FROM AUTHOR]

Artificial light at night (ALAN) can affect the physiology and behavior of animals because it alters the natural rhythm of light and darkness. Thyroid hormones (TH) are partially regulated by the light information of photoperiod and are involved in metabolic adjustments to daily and seasonal changes in the environment, such as larval and juvenile development, somatic growth and reproduction. ALAN can change photoperiodic information and might thereby lead to changes in thyroid metabolism, but so far research on this topic is scarce. Therefore, we tested in two different experiments the effects of nocturnal illumination at a wide range of light intensities on TH in plasma of Eurasian perch (Perca fluviatilis). Total 3,3′,5-triiodo-L-thyronine (T3) was significantly affected by ALAN and reduced at the highest tested intensity of 100 lx after only two weeks of exposure. Although total L-thyroxine (T4) was not significantly affected, the ratio of T3 to T4 tended to slightly decrease at 100 lx. In a second low-light experiment ALAN did not have clear effects on T3, T4 or the ratio of T3 to T4 at intensities between 0.01 lx and 1 lx. The results show first signs of endocrine disruption in thyroid metabolism after a relatively short ALAN exposure of two weeks under high-intensity streetlight conditions. Misbalanced thyroidal status can have serious implications for metabolic rates as well as developmental and reproductive processes. [ABSTRACT FROM AUTHOR]

Background and aim: Cystic thyroid nodules (CNs), although generally benign, can c ause compressive or aesthetic problems. Percutaneous ethanol injection (PEI) can represent an alternative to surgery. The present retrospective study evaluates: (i) the long-term outcome of CNs after PEI; (i i) the differences between two different PEI protocols; (iii) the CNs response according to the liquid component. Materials and methods: The study comprises 358 nodules post-PEI followed for at least 2 years. PEI was performed according to two different treatment protocols with a single (Fo ggia) or double (Turin) alcohol injection. CNs were divided according to their composition: cystic (CYS) >90%, mainly cystic (M-CYS) 75-90%, mixed (MIX) 50-75%, solidmixed (S-MIX) 35-50%. The volume reduction rate (VRR) was define d as nodule volume (mL) after PEI/nodule volume (mL) before PEI x 100. Results: The 1-year VRR was significantly higher than that at 6 months (89.5% vs 72.9%, P = 0.0005), no differences were observed after 1 year. A significant difference between Turi n and Foggia was observed only in VRR at early visit (79% vs 86%, respectively, P = 0.002) and recurrence rate (14% vs 24%, respectively, P = 0.001). Minor side-effects were infrequent. In 192 nodules with a 10-year follow-up CYS showed higher VRR than MIX and S-MIX nodules (P < 0.001). Conclusion: Our study reported that the long-term outcome of CNs treated with PEI is excellent regardless of the PEI technique utilized; the larger the cystic amount, the higher th e VRR. Based on present results, PEI can be considered as the first-line choice for treating thyroid CNs. [ABSTRACT FROM AUTHOR]

Management of Graves' orbitopathy (GO) must be based on the correct assessment of activity and severity of the disease. Activity is usually assessed with the Clinical Activity Score, whereas severity is classified according to a European Group On Graves' Orbitopathy (EUGOGO) consensus statement as mild, moderate-to-severe, and sight-threatening. Myopathic and chronic congestive forms are uncommon clinical presentations of GO. Restoration and maintenance of stable euthyroidism are recommended in the presence of GO. In moderate-to-severe disease, steroids have been widely employed and have shown to possess an anti-inflammatory activity, but about 20 - 30% of patients are not responsive and present recurrence. Some novel immunosuppressors have already been employed in clinical studies and have shown interesting results, although the lack of randomized and controlled trials suggests caution for their use in clinical practice. Potential targets for therapy in GO are the thyroid-stimulating hormone and the insulin-like growth factor 1 receptor on the fibroblasts, inflammatory cytokines, B and T cells, and the PIK3/mTORC1 signaling cascades for adipogenesis. A recent open study has shown that tocilizumab, an anti-sIL-6R antibody, inactivates GO. Consistent reports on the efficacy of rituximab have recently been challenged by randomized controlled trials. As the main goal of treatment is the well-being of the patient, the therapeutic strategy should be addressed to better suit the patient needs, more than improving one or more biological parameters. The increasing availability of new therapies will expand the therapeutic options for GO patients and allow the clinician to really personalize the treatment to better suit the patients' personal needs. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to investigate individual serum thyroglobulin (Tg) changes in relation to iodine fortification (IF) and to clarify possible predictors of these changes. Design: We performed a longitudinal population-based study (DanThyr) in two regions with different iodine intake at baseline: Aalborg (moderate iodine deficiency (ID)) and Copenhagen (mild ID). Participants were examined at baseline (1997) before the mandatory IF of salt (2000) and again at follow-up (2008) after IF. Methods: We examined 2465 adults and a total of 1417 participants with no previous thyroid disease and without Tg-autoantibodies were included in the analyses. Serum Tg was measured by immunoradiometric method. We registered participants with a daily intake of iodine from supplements in addition to IF. Results: Overall, the follow-up period saw no change in median Tg in Copenhagen (9.1/9.1 μg/l, P=0.67) while Tg decreased significantly in Aalborg (11.4/9.0 μg/l, P<0.001). Regional differences were evident before IF (Copenhagen/Aalborg, 9.1/11.4 μg/l, P<0.001), whereas no differences existed after IF (9.1/9.0 μg/l, P=1.00). Living in Aalborg (P<0.001) and not using iodine supplements at baseline (P=0.001) predicted a decrease in Tg whereas baseline thyroid enlargement (P=0.02) and multinodularity (P=0.01) were associated with an individual increase in Tg during follow-up. Conclusions: After IF we observed a decrease in median Tg in Aalborg and the previously observed regional differences between Aalborg and Copenhagen had levelled out. Likewise, living in Aalborg was a strong predictor of an individual decrease in serum Tg. Thus, even small differences in iodine intake at baseline were very important for the individual response to IF. [ABSTRACT FROM AUTHOR]

Objective: To assess thyroid function, the presence of thyroid antibodies, as well as the presence of goiter and/or nodules in subjects without a prior diagnosis of thyroid disorders, in a region with mild to moderate iodine deficiency. Design and methods: This cross-sectional study is based on data obtained from first and third visits of participants in the Sardinian survey. W e performed two different analyses. In one, we assessed the prevalence of unknown thyroid dysfunctions among 6252 subjects who had a medical examination and blood collection for assays of thyrotropin, free thyroxine, and antibodies against thyroperoxidase (AbTPO) and against thyroglobulin (AbTG). In a second analysis, we evaluated the frequency of undiagnosed goiter and nodules among 3377 subjects who had a thyroid ultrasound scan. Subjects were excluded if they had a previous history of thyroid disorders or presence of goiter and/or nodules, or thyroid surgery, or if they were taking drugs that could impair thyroid function. Results: W e found a low prevalence of overt thyroid dysfunction (hyperthyroidism 0.4% and hypothyroidism 0.7%). The rates of subclinical hypothyroidism and hyperthyroidism were 4.7 and 2.4% respectively. Almost 16% of participants were positive for at least one antibody and 5.2% for both AbTG and 0J AbTPO. Nodules were detected in 17.4% of subjects and the prevalence of goiter was 22.1%. Conclusions: Undiagnosed biochemical thyroid dysfunctions, unknown nodules, and goiter were common in subjects living in a mild to moderate iodine-deficient area. In this community, thyroid disorders often go undetected and screening could be reasonable in subjects at a higher risk [ABSTRACT FROM AUTHOR]

OBJECTIVE: The treatment of children with subclinical hypothyroidism (SH) is controversial for TSH values between 4.5 and 10 mU/l. The aim of this cross-sectional, controlled study was to evaluate growth and intellectual outcome in children with persistent SH who have never been treated with levothyroxine. DESIGN AND METHODS: Clinical and auxological parameters, thyroid function, and intellectual outcome were evaluated in 36 children with persistent SH at the age of 9.7±0.6 (range 4–18.0) years. Children had been followed longitudinally for 3.3±0.3 (range 2.0–9.3) years, from first diagnosis of SH until enrollment in the study. Thirty-six age- and sex-matched children were enrolled in the study as controls. RESULTS: At study entry, height (–0.8±0.2 SDS), bone age/chronological age (BA/CA ratio 0.92±0.6), and body mass index (BMI –0.1±0.2 SDS) in SH children were normal. Despite long-term duration of SH, none of these parameters showed a worsening with respect to height (–0.7±0.2 SDS), BA/CA (0.97±0.03), and BMI (–0.1±0.2) at the time of first SH detection. None of the children showed overt signs or symptoms of hypothyroidism during the follow-up. Verbal (99.1±2.2), performance (100.4±1.9), and full-scale (99.7±1.9) intelligence quotient (IQ) scores in SH children were normal and comparable to those of controls. No relationship was detected between IQ scores and the degree or duration of SH. CONCLUSIONS: Persistent SH in children is not associated with alterations in growth, bone maturation, BMI, and cognitive function or other complaints that could be ascribed to SH even after several years without therapeutic intervention. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Overt hypothyroidism is associated with cognitive impairment, which can be reversed if treated early and appropriately. We compared cognitive function (CF) of euthyroid older adults with those who had long-term treated hypothyroidism. METHODS: Between 1999 and 2003, the CF of 885 euthyroid and 149 hypothyroid-treated older adults (primary hypothyroidism after surgery or autoimmune thyroid disease) was assessed using three standardized CF tests: the modified mini-mental state examination, Trails B, and verbal fluency. Depressed mood was assessed using the Beck Depression Inventory (BDI). Only participants with thyroid stimulating hormone (TSH) in the normal range were included. RESULTS: The treated hypothyroid group had been treated with L-thyroxine for an average of 20 years. Those with treated hypothyroidism were older than the euthyroid group (76.1±9.6 vs 73.6±10.2 years, P=0.005) and were much more often women (81.6 vs 54.8%, P<0.001). TSH levels were similar between groups (median interquartile range=1.57 (1.19) vs 1.54 (1.59) mIU/l, P=0.81). Compared to euthyroid, the treated hypothyroidism group had more frequent antidepressant medication use (19.5 vs 8.5%, P<0.001) but similar BDI scores. Performance on the three CF tests did not differ by thyroid hormone treatment. Results were not changed after adjustment for age, sex, antidepressant medication use, exercise, and total cholesterol. CONCLUSION: Long-term treated hypothyroidism is not associated with impaired CF or depressed mood in old age. The lack of association with CF is reassuring with regard to long-term use of thyroid hormone therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) is caused by excessive hormone synthesis and release (AIT I) or a destructive process (AIT II). This differentiation has important therapeutic implications. PURPOSE: To evaluate 99mTc-sestaMIBI (MIBI) thyroid scintigraphy in addition to other diagnostic tools in the diagnosis and management of AIT. SUBJECTS AND METHODS: Thyroid Formula and 99mTc-MIBI scintigraphies were performed in 20 consecutive AIT patients, along with a series of biochemical and instrumental investigations (measurement of thyrotrophin, free thyroid hormones and thyroid autoantibodies; thyroid colour-flow Doppler sonography (CFDS) and thyroid radioiodine uptake (RAIU)). RESULTS: On the basis of instrumental and laboratory data (excluding thyroid 99mTc-MIBI scintigraphy) and follow-up, AIT patients could be subdivided into six with AIT I, ten with AIT II and four with indefinite forms of AIT (AIT Ind). 99mTc-MIBI uptake results were normal/increased in all the six patients with AIT I and absent in all the ten patients with AIT II. The remaining four patients with AIT Ind showed low, patchy and persistent uptake in two cases and in the other two evident MIBI uptake followed by a rapid washout. MIBI scintigraphy was superior to all other diagnostic tools, including CFDS (suggestive of AIT I in three patients with AIT II and of AIT II in three with AIT Ind) and RAIU, which was measurable in all patients with AIT I, and also in four out of the ten with AIT II. CONCLUSION: Thyroid MIBI scintigraphy may be proposed as an easy and highly effective tool for the differential diagnosis of different forms of AIT. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess whether methylprednisolone (MP) pulse therapy is efficacious in the treatment of moderately severe Graves' orbitopathy (GO). DESIGN: Prospective, placebo (PL)-controlled, double-blind, randomized study. METHODS: Fifteen previously untreated patients with active, moderately severe GO participated in the study; 6 patients received MP and 9 patients a PL. Moderately severe disease was defined using the NOSPECS classification of clinical signs of GO . Activity was measured with the clinical activity score (CAS). A dose of 500 mg MP or only solvent was administered intravenously, over three consecutive days, in four cycles at 4 weekly intervals (6 g of MP in total). Qualitatively, a successful treatment outcome was defined as an improvement in one major and/or two minor criteria in the worst eye at week 48. The major criteria were: improvement in diplopia grade; improvement in eye movement; a decrease in CAS of three points. The minor criteria were: decrease of eyelid retraction; decrease of proptosis; improvement in grade of soft tissue swelling; a decrease in CAS of two points. RESULTS: The qualitative treatment outcome was successful at the end of the trial in five out of six (83%) patients receiving MP and in one out of nine (11%) patients given the PL (relative risk=7.5; (95% confidence interval 1.1–49.3), P=0.005). The treatment was well tolerated. CONCLUSIONS: In spite of the small number of patients, a significant difference in outcome was observed between MP- and PL-treated patients. We conclude that MP pulse therapy appears to be an effective treatment for active, moderately severe GO. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Autoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism. OBJECTIVE: To compare the effects of the common types of therapy for Graves' hyperthyroidism on TSH-receptor autoimmunity. METHODS: Patients with newly diagnosed Graves' hyperthyroidism aged 20–55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients ≥35 years of age). L-thyroxine (L-T4) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy. RESULTS: Medical therapy (n=48) and surgery (n=47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70–80% of the patients after 18 months. Radioiodine therapy (n=36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy. CONCLUSION: The majority of patients with Graves' disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Several studies have reported the association of systemic sclerosis (SSc) with thyroid autoimmune disorders, but most of them have neither an appropriate control group nor include a complete thyroid work-up. DESIGN: The aim of our study was to evaluate the prevalence of thyroid disorders in a large number of patients with SSc using a complete clinical evaluation. METHODS: Thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroglobulin and antithyroid-peroxidase (AbTPO) autoantibodies, thyroid ultrasonography and blood flow and fine needle aspiration were performed in 202 SSc patients versus 404 gender- and age-matched controls from the general population, with similar iodine intake, to evaluate the prevalence of clinical and subclinical thyroid disorders. RESULTS: Odds ratio (OR) for female SSc versus controls was: for subclinical hypothyroidism, 3.2 (95% CI) = 1.8–5.7); for clinical hypothyroidism, 14.5 (95% CI = 2.3–90.9); for AbTPO positivity, 2.7 (95% CI = 1.8–4.1); for hypoechoic pattern, 3.2 (95% CI = 2.2–4.7); for thyroid autoimmunity, 3.7 (95% CI = 2.6–5.4); for thyroid volume <6 ml, 1.8 (95% CI = 1.2–2.7). OR for thyroid autoimmunity in male SSc versus controls was 10.8 (95% CI = 2.2–52.4). Mean values of TSH in female SSc, and of AbTPO in female and male SSc were higher (P <0.01) than in controls. We observed three cases of Graves’ disease in female SSc versus zero in controls (P = 0.0140), and two cases of papillary thyroid cancer in SSc patients. CONCLUSIONS: Thyroid function, AbTPO and ultrasonography should be tested as part of the clinical profile in SSc patients. Females, subjects with positive AbTPO and hypoechoic and small thyroid should have thyroid function follow-up and appropriate treatment in due course. [ABSTRACT FROM AUTHOR]

Vitiligo is a common skin disease characterized by depigmented maculae resulting from a reduction of the number and function of melanocytes. Many studies suggest that vitiligo might be an autoimmune disease. Vitiligo has been frequently described in association with other autoimmune diseases. Among the diseases described in association with vitiligo are the so-called autoimmune polyglandular syndromes (APS). Vitiligo can be present in all types of APS but the most frequent association appears to be in APS-3. APS-3 was defined as the association between autoimmune thyroiditis and another autoimmune disease. Here we report one patient with thyroiditis, vitiligo and autoimmune gastritis (APS-3B + C), one patient with chronic autoimmune thyroiditis, vitiligo and alopecia (APS-3C), and one case of a young patient with type 1 diabetes mellitus and vitiligo (APS-4), according to the newest classification. We stress the importance of a thorough assessment for autoimmune diseases in selected patients with vitiligo. [ABSTRACT FROM AUTHOR]

A biomonitoring study to evaluate chromosome and DNA damage respectively in somatic and germ cells of a group of male workers exposed to styrene by using biomarkers of genotoxicity was carried out. Styrene-exposed workers from three different areas of Tuscany and healthy subjects, of comparable mean age, sex and lifestyle characteristics, as a control group not exposed to chemicals, have been enrolled. In addition to previous reports [L. Migliore, A. Naccarati, A. Zanello, R. Scarpato, L. Bramanti and M. Mariani (2002) Hum. Reprod., 17, 2912–2918; L. Migliore, A. Naccarati, F. Coppedè et al. (2006) Pharmacogenet. Genomics, 16, 87–99] we present now data on a cross-sectional investigation involving a homogeneous group of subjects for which data on both somatic and germ cells have been obtained from individuals (42 exposed and 25 controls). Somatic cell genotoxicity was assessed by analysing the frequency of micronucleated binucleated cells (MNBN) in blood lymphocytes. The micronucleus assay was coupled with centromeric fluorescence in situ hybridization (FISH) analysis. Primary DNA damage in germ cells was evaluated by alkaline single-cell gel electrophoresis (Comet assay) and the percentage of the tail DNA (%TD) was used as parameter of Comet evaluation. Moreover, to investigate the frequencies of aneuploidy and diploidy in sperm, we performed multicolour FISH, using DNA probes specific for the centromeric regions of sex chromosomes and chromosome 2, in decondensed sperm nuclei of samples with normal semen parameters in a subgroup of individuals. Mandelic and phenylglyoxylic acids (MAPGA) in end of shift samples were determined as biomarkers of internal dose. MAPGA excretion was consistent with an exposure to styrene above the threshold limit value-time weighted average concentration of 20 p.p.m. Styrene workers showed significantly higher frequency of MNBN as compared to controls (13.8 ± 5.2 versus 6.2 ± 5.1; P < 0.001), due to higher proportions of both micronuclei (MN) arising from chromosomal breakage (C−MN) and harbouring whole chromosomes (C+MN). DNA damage in sperm cells was also higher among styrene-exposed, the %TD being 11.02 ± 2.99 versus 7.42 ± 2.30 in controls (P < 0.001). The incidence of aneuploidy and diploidy for the tested chromosomes in sperm did not show a statistically significant difference between workers and controls. However, a positive correlation was found between genotoxic damage detected in somatic and in germ cells, even after removing the effect of age (r = 0.475; P < 0.001). Although cytogenetic biomarkers detected both in somatic and germ cells were interrelated, no relationships were apparent with exposure parameters. Styrene exposure may increase the likelihood of both chromosome and DNA damage in somatic and germ cells, thus supporting the hypothesis of an interference on reproductive capacity among exposed workers. This is the first time that a field study shows a correlation between two biomarkers of genotoxicity evaluated at the same time in somatic and germ cells. [ABSTRACT FROM AUTHOR]

The article discusses the optimization of thyroxine replacement therapy after total or near-total thyroidectomy for benign thyroid disease. A method for monitoring and adjusting thyroid hormone replacement after surgery vary between surgical units. The thyroxine replacement therapy is instituted to restore thyroid function for benign thyroid disease. A surgical literature refers to the thyroxine dosage required for suppression of thyroid stimulating hormones after thyroidectomy.

Detection of perchlorate (ClO4−) in several drinking water sources across the U.S. has lead to public concern over health effects from chronic low-level exposures. Perchlorate inhibits thyroid iodide (I−) uptake at the sodium (Na+)-iodide (I−) symporter (NIS), thereby disrupting the initial stage of thyroid hormone synthesis. A physiologically based pharmacokinetic (PBPK) model was developed to describe the kinetics and distribution of both radioactive I− and cold ClO4− in healthy adult humans and simulates the subsequent inhibition of thyroid uptake of radioactive I− by ClO4−. The model successfully predicts the measured levels of serum and urinary ClO4− from drinking water exposures, ranging from 0.007 to 12 mg ClO4−/kg/day, as well as the subsequent inhibition of thyroid 131I− uptake. Thyroid iodine, as well as total, free, and protein-bound radioactive I− in serum from various tracer studies, are also successfully simulated. This model''s parameters, in conjunction with corresponding model parameters established for the male, gestational, and lactating rat, can be used to estimate parameters in a pregnant or lactating human, that have not been or cannot be easily measured to extrapolate dose metrics and correlate observed effects in perchlorate toxicity studies to other human life stages. For example, by applying the adult male rat:adult human ratios of model parameters to those parameters established for the gestational and lactating rat, we can derive a reasonable estimate of corresponding parameters for a gestating or lactating human female. Although thyroid hormones and their regulatory feedback are not incorporated in the model structure, the model''s successful prediction of free and bound radioactive I− and perchlorate''s interaction with free radioactive I− provide a basis for extending the structure to address the complex hypothalamic-pituitary-thyroid feedback system. In this paper, bound radioactive I− refers to I− incorporated into thyroid hormones or iodinated proteins, which may or may not be bound to plasma proteins. [ABSTRACT FROM AUTHOR]

Autoimmune polyglandular syndromes (APS) are conditions characterized by the association of two or more organ-specific disorders. Type 2 APS is defined by the occurrence of Addison's disease with thyroid autoimmune disease and/or Type 1 diabetes mellitus. Clinically overt disorders are considered only the tip of the autoimmune iceberg, since latent forms are much more frequent. Historical, clinical, genetic, and immunological aspects of Type 2 APS are reviewed. Furthermore, data on 146 personal cases of Type 2 APS are also reported. [ABSTRACT FROM AUTHOR]

Background: Occupational exposure to toxic agents may cause infertility, congenital anomalies or death in offspring, but few studies have evaluated DNA integrity in germ cells of male workers. We investigated sperm DNA integrity in individuals occupationally exposed to styrene.Methods and Results: Semen samples were obtained from 46 male workers exposed to styrene and 27 unexposed controls (age range 18-45 years). Exposed individuals had worked for at least 2 years in the last 5 years and continuously for 6 months in factories producing reinforced plastics. The Comet assay was performed to evaluate DNA integrity in sperm, as well as semen quality analysis to assess sperm concentration and morphology. There were no differences in the results of the standard semen analysis between exposed subjects and the reference group. However, we found a significant difference (P < 0.001) in sperm DNA damage by the Comet assay between exposed subjects and the reference group.Conclusions: The Comet assay proved to be sensitive in detecting an alteration in DNA integrity in germ cells of workers exposed to styrene. This finding contributes towards the understanding of the importance of male occupational exposure within the context of genetic risk assessment in humans. [ABSTRACT FROM AUTHOR]

Autoantibodies directed against human CD38 (an enzyme catalysing the interconversion of NAD+ and cyclic ADP-ribose) have been demonstrated recently in patients with type 2 diabetes. We tested 220 consecutive Caucasian patients with autoimmune chronic thyroiditis, 104 patients with Graves' disease, 220 subjects from the general population (control I) and 78 healthy control subjects not affected by thyroid autoimmune disorders (control II) for the presence of anti-CD38 autoimmunity. Using Western blot analysis and optical densitometry, a specific band corresponding to human recombinant CD38 was identified in the serum of several subjects. By defining anti-CD38 positivity as a standardized optical reading > 3 s.d. higher than the mean value of control I, 10·4% of patients with thyroiditis and 7·7% of Graves' patients were anti-CD38 positive (P = 0·0009 versus 1·8% of control I). Similarly, 13·1% of patients with thyroiditis and 10·5% of Graves' patients had a standardized optical reading > 3 s.d. higher than the mean value of the subjects not affected by thyroid autoimmune disorders (P = 0·002 versus 1·2% of control II). Anti-CD38 autoimmunity did not differ between euthyroid, hyperthyroid or hypothyroid patients or between patients with or without thyroid hypoechogenicity. Anti-CD38 autoantibodies were associated with higher levels of circulating antithyroid-peroxidase antibodies (P = 0·03) and they were more frequent in Graves' patients with ophthalmopathy (P < 0·05). Anti-CD38 autoantibodies are a new autoimmune marker in chronic autoimmune thyroiditis and Graves' disease. The specific role of CD38 and its autoantibodies in the modulation of thyroid cell function or growth remains to be investigated. [ABSTRACT FROM AUTHOR]

Type I polyglandular autoimmune syndrome is characterized by the triad of hypoparathyroidism, Addison's disease and chronic mucocutaneous candidiasis. Chronic active hepatitis has been associated with this syndrome but its incidence and severity have not been well documented. We describe a sibship of two patients with type I polyglandular autoimmune syndrome who presented with autoimmune chronic active hepatitis. The first patient presented to us with advanced disease and died despite an emergent liver transplant, while the second patient responded to steroids. Autoimmune chronic active hepatitis, a major cause of mortality in this syndrome, can present without symptoms or physical signs of liver disease. We suggest periodic screening of liver enzymes in subjects with this syndrome. [ABSTRACT FROM PUBLISHER]

In the present report the mechanisms responsible for the expression of the thyroid microsomal autoantigen (M-Ag) were studied in primary cultures of human thyroid cells prepared from Graves' or non-toxic goitres. The indirect immunofluorescence (IFL) technique using human sera positive for anti-microsomal antibody (anti-MAb) was employed to detect M-Ag. Studies were performed to ascertain whether M-Ag recognized by anti-MAb could be identified with thyroid peroxidase (TPO). Preabsorption experiments showed that, similarly to solubilized thyroid microsomes, purified human TPO abolished the binding of anti-MAb to thyrocytes, while no inhibition was obtained with control human tissues. The identity of M-Ag and TPO was also demonstrated using a double layer IFL technique which allowed a simultaneous staining of the antigen(s) recognized by anti-MAb and by a monoclonal anti-TPO antibody. After 5-15 days of TSH withdrawal from the culture medium the M/TPO-Ag disappeared from the surface and the cytoplasm of human thyroid cells. Readdition of TSH (0.1-100 mU/ml) to cells lacking M/TPO-Ag elicited its reappearance within 48-72 h. This effect of TSH was prevented by 10 μM cycloheximide but not by methimazole (0.1-2 mM). Two stimulators of the adenylate cyclase-cAMP system, cholera toxin and forskolin, and 8-bromo-cAMP mimicked TSH in inducing M/TPO-Ag. Thyroid stimulating antibody (TSAb) of Graves' disease also reproduced the effect of TSH on M/TPO-Ag reexpression in human thyroid cells. By contrast, epidermal growth factor, oestradiol or NaI were ineffective in inducing M/TPO-Ag. The present data indicate that: (i) the expression of M/TPO-Ag in human thyroid cells is dependent on TSH stimulation, through pathways which involve cAMP production and protein synthesis, (ii) TSAb reproduces this effect of TSH; (iii) oestradiol and NaI have no direct influence on the expression of M/ TPO-Ag. [ABSTRACT FROM AUTHOR]

Human thyroid cells in primary culture were used for studies of thyroid cell surface antibodies in patients with thyroid autoimmune disorders. Radioiodinated IgG preparations containing thyroid microsomal antibody (TMAb), thyroid stimulating antibody (TSAb) and/or thyroglobulin antibody (TgAb) were tested for binding to thyroid cells. Binding was observed with radioiodinated IgG from patients with Graves' disease, Hashimoto's thyroiditis and idiopathic myxoedema containing TMAb. irrespective of the presence of TSAb and TgAb, while negative results were obtained with normal IgG. A dose-dependent inhibition of binding to thyroid cells was produced by the addition of the corresponding unlabelled IgG preparations. Evidence for tissue specificity was provided by the absence of binding to human skin fibroblasts used as controls. Preabsorption with human thyroid microsomes completely abolished the binding to thyroid cells of a radioiodinated TMAb positive IgG preparation, while only incomplete removal of the reactivity to thyroid microsomes was produced by preabsorption with thyroid cells. These data suggest that some but not all microsomal antigenic determinants are expressed on the thyroid cell surface. Binding to thyroid cells was also observed with purified TgAb. indicating that thyroglobulin antigenic determinants are present on the surface of thyroid cells. No evidence of binding was obtained with a TSAb positive Graves' IgG preparation with undetectable TMAb and TgAb. Unlabelled IgG preparations containing TMAb from patients with either Hashimoto's thyroiditis or idiopathic myxoedema were shown to inhibit the binding to thyroid cells of radioiodinated TMAb positive Graves' IgG and vice versa. These data indicate that antibodies present in these thyroid autoimmune disorders share common thyroid cell surface antigens. However, the binding of radioiodinated IgG from a patient with idiopathic myxoedema was only partially inhibited by Graves' or Hashimoto's IgG, suggesting that some of the thyroid cell surface antibodies of idiopathic myxoedema may not be detectable in other thyroid autoimmune disorders. [ABSTRACT FROM AUTHOR]

Abnormalities of thyroid function are associated with changes in lipid concentrations and in the incidence of ischaemic heart disease. Whether lipid concentration and thyroid function are related when thyroid function is normal in ischaemic heart disease is uncertain. This study was undertaken to investigate the relationship between thyroid function, serum lipids and ischaemic heart disease in euthyroid women. Forty-six euthyroid patients were studied. Patients with diseases known to affect lipid levels or receiving drugs known to alter lipid or thyroid metabolism were excluded Twenty-three had ischaemic heart disease (IHD) and were matched with 23 controls. Correlations were found between thyrotropin (TSH) and cholesterol (=0·05) low density lipoprotein (LDL) (=0·09) and triglyceride (=0·009 in the IHD group but not between any serum lipids and TSH in the control group. Analysis of covariance showed a statistically significant difference between groups of the association between cholesterol and TSH (<0·05 (slope) <0·001 (means)), LDL and TSH (<0·005 (means)) and between triglyceride and TSH (<0·05 (means)). This study suggests that TSH within the normal range is having a statistically significant effect on lipid levels in women with ischaemic heart disease. [ABSTRACT FROM PUBLISHER]

The objectives of this study were to describe changes in asthma and employment after diagnoses of occupational asthma reported to the SWORD project. Questionnaires were sent to 312 physicians for all 1,940 cases of occupational asthma reported from 1989–92; 1,769 (91%) were returned but information was available for only 1,317 (68%). Of patients reported by occupational physicians, 45% had recovered from asthma compared to only 14% of those reported by chest physicians (excluding medicolegal cases), presumably because of differences in severity. Proportions with the same employer were 49% and 48% respectively. Patients exposed for a year or more after diagnosis recovered from asthma less frequently but were more often employed than those exposed for less than a year. Among those whose asthma was attributed to high molecular weight agents, smokers had developed asthma earlier after exposure began than others but had the best prognosis. Asthma developed following a single high exposure in 18 cases (2%), of which 13 were to irritants and five to known sensitizers. [ABSTRACT FROM PUBLISHER]

The three-dimensional organization of the smooth musculature around the human ampulla is revealed by means of scanning electron microscopy after NaOH maceration and ultrasonic microdissection of the interstitial connective tissue. The muscular wall of the ampulla appears as a continuous network of randomly anastomosed smooth muscle cell bundles that showed a multidirectional arrangement. The smooth muscle cell bundles modify their orientation along their course, intertwine repeatedly with each other and dichotomize, generating new bundles with a different orientation from that at the origin. These results demonstrate that the myosalpinx of the human ampulla is not organized into clear cut longitudinally, circularly or spirally arranged layers, as suggested in previous light microscopy studies. In contrast, the presence of a network of multidirectional smooth muscle cell bundles revealed in this study suggests that there is no morphological evidence for unidirectional peristalsis, and that the musculature is probably structurally designed to stir rather than push the tubal contents. These morphological findings better explain the random pattern of propagation of the contraction waves and the electrical impulses through the smooth musculature of the human ampulla, as postulated in early experimental physiological studies. Further, they suggest a specific function for the ampullar musculature which may not be only strictly related to tubal content transport. [ABSTRACT FROM PUBLISHER]

The pineal gland is an important transducer mediating environmental influences on endocrine organs. It has direct effects on the hypothalamus and pancreas and indirect effects on the pituitary, adrenal, thyroid, and testes. Thus, specific endocrine rhythms are affected by alterations in trophic hormone secretion by the hypothalamus-pituitary complex, direct effects on biochemical transformations within target organs, or by alterations in metabolism and excretion of hormones by the liver. Target enzymes common to the above organs for melatonin and arginine vasotocin (AVT) are 5α-reductase, monoamine oxidase (MAO), and smooth muscle enzymes. Melatonin selectively inhibited 17rβ ol-dehydrogenase activity and 5α-reductase activity while 17rβ ol-dehydrogenase was stimulated by serotonin (5-HT). Other steroid biotransformations were inhibited by both 5-HT and melatonin. Evidence from the pancreas and insulin secretion, liver and glucuronosyl transferase activity, and hypothalamic and pituitary studies indicate that melatonin mediated some of its effects on these organs through MAO activity and 5-HT levels. There were some species and tissue differences with respect to the effects of melatonin and AVT on MAO activity and steroid biotransformations. Melatonin stimulated steroid biotransformations in the duck, while MAO activity and 5α-reductase activity in the hamster responded differently to melatonin than did similar preparations from the rat. [ABSTRACT FROM PUBLISHER]

The article lists authors who contributed to papers that appears in the December 1978 issue of the journal "Clinical & Experimental Immunology." Some of the authors listed are J.D. Almeida, C.M. Arroyave, J.J. Baker, W.E. Wright, S.P. Chan, J.J. Oppenheim, P. Cornillot, B. Danneman, B.J. De Souza, H.M. Dosch, J.W.W. Lee, E.W. Gelfand, J.A. Falk, J.I. Gallin, E.W. Gelfand, T. Godal, Lynn Greenberg, S.V. Payne, D. Moore, J.F. Mowbray, G.R. Mirick, M. Meurer, E. Penner, B. Albini, F.I. Milgrom, P.H. Lambert, L. Layward, M.E. Kaplan, R.A. Kaplan and Lida Ivanyi.