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This is a comprehensive study of the photophysical behaviour of heteroleptic iridium(III) complexes with imidazo[4,5-f][1,10]phenanthroline (imphen) as an ancillary ligand, represented by the general formula [Ir(N∩C)2(imphen)]PF6. As cyclometalating ligands, 2-phenylpyridine (Hppy), 2-phenylquinoline (Hpquin), 2-phenylbenzothiazole (Hpbztz), and 2-(2-pyridyl)benzothiophene (pybzthH) were used. The impact of structural modifications of cyclometalating ligands was widely explored by a combination of steady-state and time-resolved optical techniques accompanied by theoretical calculations. We evidenced that the cyclometalating ligands induce essential changes in the nature of the emissive excited state and the emission characteristics of [Ir(N∩C)2(imphen)]PF6. While the complex [Ir(ppy)2(imphen)]PF6 (1) is a typical 3MLLCT emitter, the lowest triplet states of [Ir(pquin)2(imphen)]PF6 (2), [Ir(pbztz)2(imphen)]PF6 (3) and [Ir(pybzth)2(imphen)]PF6 (4) have a predominant 3LCN∩C character. The phosphorescence colour of the investigated Ir(III) complexes changes from greenish-yellow to red, their quantum yields vary from 56 to 2%, and their triplet excited-state lifetimes fall in the 743–3840 ns range. The highest photoluminescence quantum yield was revealed for 2 in CH2Cl2, while complex 3 in MeCN shows the most pronounced increase in the lifetime. Both complexes 2 and 3 show an increased efficiency of singlet oxygen generation. The herein discussed structure–property relationships are of high significance for controlling photoinduced processes in heteroleptic iridium(III) complexes with the imphen-based ancillary ligand, and making further progress in effectively tuning the emission energies, quantum yields and excited-state lifetimes of these systems by structural modifications of cyclometalating ligands, especially the π-conjugation, the position of the N-donor and the presence of sulfur heteroatoms. [ABSTRACT FROM AUTHOR]

In this study, we examined the photophysical properties of an azacrown–iridium(III) complex while focusing on its interactions with calcium ions (Ca2+). We explored the dynamic processes within the complex combining time-dependent density functional theory (TDDFT) calculations and time-resolved spectroscopies. In the presence of Ca2+, the complex exhibits significant shifts in absorption and emission profiles, from 494 nm to 375 nm, aligning with theoretical predictions. Notably, we observed the ultrafast photo-ejection of Ca2+ within 70 femtoseconds, followed by its recapture in 250 nanoseconds, revealing a 10-million-fold timescale difference between the two phenomena. These behaviors confirm the established photophysical properties of polypyridyl iridium(III) complexes and their intrinsic sensitivity to their surrounding environment. Our comprehensive kinetic analysis highlights the azacrown moiety's competitive binding and photo-release capabilities, suggesting its potential for practical sensing applications. The versatile properties of these iridium(III) complexes offer promising prospects for their application as stimuli-responsive materials and in advanced optoelectronic devices, targeted imaging, and biomedical ion sensors and delivery systems. [ABSTRACT FROM AUTHOR]

(1) Background: Exploring the relationship between spontaneous breathing patterns and aerobic and anerobic running exercise performance can greatly improve our understanding of optimizing physical fitness. Spontaneous breathing patterns refer to how the rhythm and depth of breathing affect performance and physical adaptation during exercise. (2) Methods: This study aimed to investigate this relationship by enrolling 240 college students (120 males and 120 females, aged 18–22). We evaluated their resting respiratory rate (RR), the combined total of abdominal and thoracic movements (AM+TM), the proportion of abdominal movement to the overall respiratory movement (AM/(AM+TM)), and the inhalation to exhalation ratio (I/E ratio). Additionally, their performance in a 50 m sprint (measuring anerobic capability), an 800- or 1000 m run (assessing mixed aerobic and anerobic capacity), and a 12 min distance run (evaluating aerobic capacity) was recorded. (3) Results: Our findings, through both correlational and comparative analyses, indicate that a larger AM+TM is predictive of a greater distance covered in the 12 min run, suggesting enhanced aerobic capacity. Interestingly, among female participants, a lower body mass index (BMI) coupled with a higher proportion of abdominal movement (AM/(AM+TM)) was linked to better performance in the 800 m run, indicative of superior mixed aerobic and anerobic capacities. These results imply that women with a larger tidal volume and those with a lower BMI but higher abdominal contribution to breathing at rest may exhibit better aerobic and mixed exercise capacities, respectively. (4) Conclusions: Based on these findings, we recommend that healthcare professionals and physical education instructors incorporate respiratory pattern assessments into their practices to potentially improve the physical health of their clients and students, with a particular emphasis on female populations. This study underscores the importance of understanding the intricate relationship between spontaneous respiratory patterns and exercise capabilities in enhancing overall physical fitness and health. [ABSTRACT FROM AUTHOR]

The rate constants for the reaction of hydroperoxyl (or perhydroxyl) radical HOO˙ with fifteen phenols and ascorbyl palmitate were measured in acetonitrile at 37 °C by evaluating the effect that the antioxidants had on the rate of autoxidation of γ-terpinene. The HOO˙ radical represents an important reactive species that can be formed by protonation of superoxide anions (O2˙−) or by fragmentation of alkylperoxyl radicals (ROO˙) formed during the autoxidation of pro-aromatic derivatives like γ-terpinene. The phenols investigated in this study include natural compounds like phenolic acids (protocatechuic, caffeic and dihydrocaffeic acids), flavonoids (3-hydroxyflavone, pinobanksin, galangin, catechin, luteolin, quercetin, 6-methoxyluteolin), 4-methylcatechol and antioxidant additives ascorbyl palmitate and the a-tocopherol analogue 2,2,5,7,8-pentamethyl-6-chromanol. The rate constants for the reaction of HOO˙ with the above compounds (kinh) spanned from 1 × 103 M−1 s−1 for the unsubstituted phenol, to 7 × 104 and 9 × 104 M−1 s−1 for 4-methylcatechol and ascorbyl palmitate, respectively. As in a typical Evans–Polanyi plot, the log(kinh) was found to be inversely proportional to the bond dissociation enthalpy of the reactive OH. The comparison of the results with the data reported in the literature shows an unusual kinetic solvent effect that enlightens the unique behavior of HOO˙ and provides a rationale for the superior radical trapping ability of catechols and ascorbyl palmitate. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the usefulness of submitting children with thyroid cancer secondary to nuclear accidents to a completion total thyroidectomy., Design: A case series consisting of patients living and operated on in Belarus whose parents had asked for a clinical evaluation in a western European center., Setting: A tertiary care referral center., Patients: The conditions of 47 children from Gomel, Belarus, with differentiated thyroid carcinoma following the nuclear accident at Chernobyl, Ukraine, were evaluated at the University of Pisa, Pisa, Italy. In approximately half of the cases, the treatment in Belarus consisted of a hemithyroidectomy. After a complete evaluation, the decision was made to reoperate on 19 of them by performing a completion total thyroidectomy. The preoperative evaluation revealed that 5 (26%) of the 19 patients who had undergone a hemithyroidectomy had unilateral recurrent nerve palsy and that 2 (10.5%) had hypoparathyroidism., Interventions: Neck ultrasonography was used for the preoperative localization of thyroid residuals, thyroid nodules, suspicious lymph nodes, and a guided fine-needle aspiration biopsy specimen. The circulating thyroglobulin measurement was obtained before reoperation. An iodine 131 whole-body scan (WBS) was performed and circulating thyroglobulin levels were obtained after completion of the thyroidectomy during withdrawal of levothyroxine sodium therapy., Main Outcome Measure: The number of patients with a recurrence of thyroid cancer and lung or lymph node metastases after the completion total thyroidectomy., Results: The results of the histologic examination were positive for papillary thyroid cancer in 6 (28.6%) of 21 patients, 3 with residual cancer in the remaining thyroid lobe and 3 with metastatic lymph node disease. A posttherapy WBS demonstrated lung metastases in 5 (28%) of 18 patients and lymph node metastases in 6 (33%) of 18 patients; the results of a posttherapy WBS were negative for metastases in 7 (39%) of 18 patients. Hypoparathyroidism developed in 4 (21%) of 19 patients who underwent a completion total thyroidectomy; unilateral laryngeal nerve palsy developed in 1 (5.2%) of these 19 patients. Among 22 children who previously underwent total thyroidectomy in Belarus, a diagnostic WBS showed lung metastases in 10 (45%) of the children and lymph node metastases alone in 3 (14%) of the children; the results of a diagnostic WBS were negative for metastases in 9 (41%) of the children. Statistical analysis showed a nonsignificant (P>.05) difference in the prevalence of lung and lymph node metastases in patients who previously underwent total thyroidectomy compared with patients who underwent completion total thyroidectomy., Conclusion: Completion total thyroidectomy allowed for the diagnosis and treatment of recurrent thyroid cancer and lung or lymph node metastases in 61% (11/18) of the patients in whom residual differentiated thyroid carcinoma was not previously recognized.

We compared the effectiveness of systemic corticosteroids with the use of high-dose intravenous immunoglobulin (IVIG) in the treatment of Graves' ophthalmopathy. This was performed as a prospective, nonrandomized study including a blinded ophthalmological and orbital computed tomographic (CT) evaluation. The two groups of patients were not significantly different in relation to sex composition, age distribution, duration of Graves' disease, and ophthalmopathy and previous hyperthyroidism. All patients were followed up by endocrinologic evaluation and blinded ophthalmological (before therapy = B, at the end of therapy = E, and 6 months after the end = 6M) and orbital CT (B and E) evaluations. Twenty-seven patients treated with IVIG were followed up after the end of treatment for an average of 21 months (range 12 to 48 months). Soft tissue involvement (NOSPECS) improved or disappeared in 32 of 35 (90%) patients treated with IVIG and in 25 of 27 (92.5%) patients treated with corticosteroids. Diplopia improved or disappeared in 22 of 29 (75%) patients treated with IVIG and in 16 of 20 (80%) patients treated with corticosteroids. The results observed by clinical evaluation were confirmed with orbital CT score in 30 IVIG patients and in the corticosteroid-treated patients; a significant reduction of extraocular muscle thickness was observed after treatment in both groups. Proptosis improved or disappeared in 20 of 31 (65%) patients treated with IVIG and in 15 of 24 (62%) patients treated with corticosteroids. Mean values of proptosis evaluated by Hertel's exophthalmometer showed a slight reduction both in IVIG as well as in corticosteroid-treated patients. It is interesting to observe that in 28 IVIG-treated patients in whom it was possible to evaluate soft tissue involvement, proptosis and diplopia in the period between the fifth and sixth month from the start of therapy, the most important part of the amelioration (if responders) was already obtained at that time. Responder patients were defined in relation to the decrease in the highest NOSPECS class or grade. Among IVIG-treated patients 26 of 34 (76%) responded; while in the corticosteroid group 18 of 27 (66%) responded to treatment. The prevalences of patients who responded to the treatments were not significantly different in the two groups (Chi-square). The initial values of the subjective eye score were similar in the two groups, and a significant reduction was observed in both. Major side effects requiring discontinuation of the corticosteroid therapy were observed in two patients with hemorrhagic gastritis and in one patient with manic-depressive psychosis. Among 15 patients submitted to the evaluation of bone mineral content before and after corti-costeroid therapy, 4 presented signs of osteoporosis and 3 a reduction of bone mineral content. Moderate and minor side effects were more frequently noted in steroid-treated patients than in the IVIG group. These data suggest that IVIG is safe and effective in reducing the eye changes in patients with Graves' ophthalmopathy.

To evaluate the presence of asbestos-related pleural and parenchymal abnormalities and their correlation with pulmonary function and smoking habits, 119 asbestos-exposed asymptomatic workers (mean age, 46.2 years; mean duration of asbestos exposure, 8.6 years; mean latency time, 21.6 years) with normal standard P.A chest radiographs were submitted to HRCT, CO-diffusing capacity and pulmonary function tests. HRCT scans were normal only in 31 (26%) examined workers; 31 (26%) subjects showed both pleural and parenchymal involvement, and 50 (42%) and seven (6%) had exclusively pleural and parenchymal abnormalities, respectively. Based on CO-diffusing capacity and pulmonary function tests, no significant difference was demonstrated between workers with pleural lesions and subjects with normal pleura; however, lower values of FVC were observed in the nonsmoking workers with parenchymal abnormalities in comparison with nonsmoking subjects with normal parenchyma (78.2 vs. 89.7% of predicted values; p = 0.03 by student's two-tailed t test), and lower values of FEV1/FVC in the smokers with parenchymal lesions with respect to smokers with normal parenchyma (93.7 vs. 100.2% of predicted values; p = 0.005 by students' two-tailed t test). In conclusion, our results demonstrate that HRCT may detect early parenchymal abnormalities which correlate with exposure to asbestos and respiratory function impairment, including a reduction in obstructive indices in smokers occupationally exposed to asbestos, without any clinically evident disease.

This study reviews the epidemiology of thyroid cancer during childhood from the environs of Gomel in Belarus and the clinical data of 64 children aged 4 to 16 years from this area who had been diagnosed with differentiated thyroid carcinoma following the nuclear accident of Chernobyl. One case of thyroid cancer in children (aged < 15 years at diagnosis) was observed during the period 1981-1985 (rate = 0.5; expressed as annual averages per million children under age 15 years in the region of Gomel and period identified) before the Chernobyl accident. Twenty-one cases of thyroid cancer in children were observed during 1986-1990 (rate = 10.5) and 143 (rate 97) during 1991-1994 after the Chernobyl accident. During the first 7 months of 1995, there were 33 more cases of thyroid cancer observed in children. Three children with thyroid cancer were born since 1986 in the Gomel region. A total of 64 children aged 4 to 16 years from this area who had been diagnosed with differentiated thyroid carcinoma had been reviewed by us during the period May to November 1994. The female/male ratio was 1.4:1.0. At the time of the first diagnosis the mean age of the children was 9.4 +/- 2.8 years, and at the time of the accident their mean age was 3.8 +/- 2.4 years. More than 90% of the patients were less than 6 years of age and 3 were still in utero at the time of the accident. The period of latency between the accident and the first diagnosis was 5.6 +/- 1.5 years. Their ages at the time of the first diagnosis and their ages at the time of the accident were significantly correlated (p = 0.001); there was no significant correlation between the age of each child at the time of the accident and the latent period before the onset of carcinoma. The aggressiveness of the tumor, evaluated on the basis of T stage, lymph node status, and lung metastases, did not correlate with age at the time of the first diagnosis or with the age at the time of the accident. The susceptibility of the thyroid to the carcinogenetic effects of radiation, particularly during the first years of life (< 5 years) has clearly been demonstrated. However, there appears to be no correlation between the aggressiveness of the tumor and the age of the patients.

The prevalence of thyroid nodules was studied with ultrasonography in a group of male hospital workers (n = 44) who had been exposed occupationally to x-rays. This group was compared with a group of nonexposed workers (n = 88) who were age- and sex-matched with the exposed workers. Thyroid nodules were detected in 18 (41%) of the exposed workers, compared with 11 (13%) of the nonexposed controls. Both groups were subdivided with respect to age (i.e., 30-39 y, 40-49 y, 50-59 y), and there was a higher and significant relative risk for thyroid nodule formation in the exposed group. We also divided the groups into subgroups according to levels of exposure (i.e., nonexposed, exposed for < 20 y, and exposed for > 20 y), and a significant result was obtained with the linear-trend chi-square test. The preliminary results of our study suggest that occupationally induced exposure to radiation may be a risk factor for thyroid nodule formation.

Objective: To study the involvement of antibodies in the extrathyroidal manifestations of autoimmune Graves' disease, we determined the presence of IgG, IgA and IgM antibodies and C3c in connective tissue samples from patients with Graves' disease and pretibial myxedema (PTM) or thyroid associated ophthalmopathy (TAO)., Methods: Connective orbital tissue samples were obtained from 12 patients undergoing orbital decompression for TAO, and skin samples from lesions on the pretibial area were obtained in 7 patients with PTM. Sections from each tissue sample were stained with fluorescin-isothiocianate conjugated anti-human IgG, IgA, IgM and C3c and were examined by a fluorescence optical instrument. Other serial sections from each sample were incubated with human IgG solutions (concentration 6 mg/ml or 20 mg/ml), human albumin (40 mg/ml), PBS, myoglobin (40 mg/ml), or IgA (20 mg/ml), and were then processed by a standard direct immunofluorescence staining procedure., Results: Among the samples from TAO patients 8/12 (67%) were positive for IgG deposition, 4/9 (44%) were positive for IgA, 1/9 (11%) was positive for IgM and 4/9 (44%) were positive for C3c deposition. Orbital connective samples from 3 non-TAO patients were all negative. Among samples from PTM patients 4/7 (57%) were positive for IgG deposition, 3/ 4 (75%) were positive for IgA, 0/4 was positive for IgM and 3/7 (43%) were positive for C3c deposition. Skin samples from 5 control patients undergoing skin biopsy for non-autoimmune diseases were all negative. Incubation with human IgG (20 mg/ml) resulted in the complete disappearance of IgG and C3c deposition in all positive patients. No significant variation in IgG fluorescent staining after incubation with either 6 mg/ml of IgG solution, human albumin, PBS, myoglobin or IgA was observed., Conclusion: The results of our study suggest that different classes of antibodies, mainly IgG and IgA, may be implicated in the disease process in autoimmune TAO and PTM. Activation of the complement cascade, via the classic or the alternative pathway, could take place in about 40% of these patients. IVIG in vitro may solubilize, by a specific mechanism, IgG and complement immune complex deposition in the extrathyroidal manifestations of autoimmune Grave's disease.

The aim of the study was to evaluate the role of neck ultrasonography in follow-up of patients with differentiated thyroid cancer. Sixty-three patients had total thyroidectomy and 131I ablation for differentiated thyroid cancer and had a negative whole body scan during follow-up. They were admitted for a high resolution neck ultrasound examination. Sixteen of 63 patients presented images suspicious for lymph node metastasis and/or for local recurrences (4 cases). Fine needle aspiration confirmed the suspicion of malignancy in 12 patients: only lymph node metastasis in 8 cases, local recurrence and lymph node metastasis in 3 cases, and in one case only local recurrence. Fine needle aspiration was suspicious for lymphadenitis in 4 cases. Thyroglobulin levels were very high in all patients with local recurrence and/or lymph node metastasis but undetectable in 2 cases presenting node metastasis and in 4 cases with lymphadenitis. All but one patient were admitted for surgery and the cytological diagnosis was confirmed. Early identification of a pathologic mass in the neck is a desirable goal; high resolution echography can play an important role in the follow-up of these patients and can detect local recurrences even when there is a negative whole body scan or undetectable thyroglobulin level.

Seven patients affected by Graves' ophthalmopathy and pretibial myxedema (four patients with nodular form, two with diffuse, and one with elephanthiasic form) have been treated with high-dose intravenous immunoglobulins. We have observed (a) clinical improvement of pretibial myxedema and Graves' ophthalmopathy in all patients, (b) a reduction of pretibial skin thickness, by ultrasonography evaluation, in four patients, (c) a reduction of mucopolysaccharide skin content in three patients, (d) disappearance of lymphocytic skin infiltration and IgG deposition in two patients, and (e) a parallel reduction of the titer of circulating autoantibodies as antithyroglobulin, antimicrosomal, anti-TSH receptor, and of non-organ-specific antibodies as antinuclear, anti-smooth muscle cells, and anti-mitochondrial. In comparison two patients with Graves' ophthalmopathy and pretibial myxedema treated with systemic corticosteroids did not present any improvement of the cutaneous ailment. Therefore, this study suggests that intravenous immunoglobulins are effective in the treatment of pretibial myxedema and may have an immunomodulant action in patients with Graves' disease and related disorders.

We compared the results of ethanol sclerotherapy in thyroid cysts with emptying of cysts and instillation of saline. Twenty-six patients with recurrent thyroid cysts were treated with cyst aspiration and subsequent ethanol sclerotherapy. A control group of 44 patients was submitted to cyst aspiration and subsequent injection with isotonic saline; among them 20 had previously been treated with repeated aspirations of the cyst fluid. The patients were followed up clinically and ultrasonically 1 and 12 months after treatment. Cure was defined as the absence of any residual cystic lesion or an ultrasonic cyst volume less than 50% of basal after 12 months from the start of treatment. Cytological study showed all of the lesions to be benign. Of the 44 patients in the saline group 16 (36%) were cured, among whom 6 of 20 had previously been submitted to repeated aspirations. Among the 26 patients treated with ethanol sclerotherapy 20 (77%) were cured. Statistical analysis revealed a significantly higher effectiveness of treatment with ethanol than that with emptying and saline instillation (chi-square, P = 0.002) or with repeated aspiration and saline instillation (chi-square, P = 0.003). Slight pain was observed in two patients treated with saline and five treated with ethanol sclerotherapy. Three patients treated with ethanol sclerotherapy presented severe pain and one transitory hyperthyroidism. We conclude that ethanol sclerotherapy is effective and safe in the treatment of thyroid cysts.

The possibility to detect initial "preclinical" pulmonary lesions related to asbestos is under debate. The aim of this study is to report our experience. We have submitted to HRCT 70 shipyard workers with chest X-ray judged "normal" by "outside" readers (mean age 44.5 +/- 6.1 ys) with a similar grade of (low-level) exposure to amosite (mean duration of "direct"/"heavy" exposure was 4.2 +/- 4.9 ys; "environmental"/"light" exposure was 8.4 +/- 5.9 ys). Among the 70 workers, in 34 pleural plaques were shown, in 6 subjects parenchymal abnormalities alone and in 13 parenchymal and pleural abnormalities were found; in the last 17 workers no pathological finding was shown. In six subjects the presence of a combination of parenchymal abnormalities permitted us to diagnose asbestosis. The difference in the duration of exposure to asbestos for the subjects with both pleural and parenchymal involvement compared to all other groups of workers was statistically significant; also the difference in duration of exposure between workers with or without parenchymal involvement resulted significant. In a control group (20 subjects without any known professional exposure to asbestos) HRCT permitted us to identify 5 cases with small pleural plaques while only one case presented parenchymal bands; lesion frequency was significantly lower in comparison with the exposed group. Calcified plaques have been proved to be more common in the workers with heavier exposure, and no one of the reference group had calcified plaques. The CT-determined emphysema score was found to optimally correlate with smoking habit (pack/years). In conclusion our study suggests that pulmonary or pleural involvement can be shown by HRCT before the onset of any clinical symptomatology with high sensitivity and specificity. Furthermore the results seem to indicate that the prevalence of HRCT-shown parenchymal lesions and the severity of lung involvement among asbestos-exposed workers are related to the duration of exposure, as in most of clinically evident asbestos-related lung disorders, in contrast with previous observations.

We have reexamined a series of 1119 patients consecutively submitted to fine needle aspiration of nodules of the neck. Among these in 166 cases ultrasonography combined with aspiration suggested the presence of cysts. 60 patients were submitted to cyst aspiration and 34 were aspirated and submitted to cyst injection with tetracycline hydrochloride. The patients were followed up clinically and ultrasonically 3 and 12 months after treatment. Cure was defined as the absence of any residual cystic lesion and an ultrasonic cyst volume less than 50% with respect to basal after 12 months from the start of treatment. 18 of the 60 (30%) patients only aspirated and 24 of the 34 patients (70%) in the tetracycline group were cured (statistically significant; p < 0.005). We conclude that tetracycline seems an effective sclerotherapy in treatment of thyroid cysts.

The lungs of 50 symptom free workers exposed to amosite and with normal pulmonary function tests were examined by high resolution computed tomography (HRCT). Twenty five had normal standard chest radiographs whereas the other 25 had radiographs interpreted as near normal (International Labour Office profusion score < 0/1 or suspected pleural plaques). In 13 of the workers the results of HRCT were negative; in 22 pleural plaques were found, in five there was only parenchymal involvement, and 10 had both pleural and parenchymal changes. The mean duration of exposure to amosite was significantly longer for the subjects with parenchymal signs than for those with normal parenchyma and for the workers with pleural plaques than for those with normal pleura and lung parenchyma. The prevalence of identified pleural and parenchymal abnormalities in the 50 workers was also significantly higher than in a reference group without exposure to asbestos. It is concluded that HRCT may detect initial lung and pleural involvement in symptom free workers exposed to amosite and the mean duration of exposure is longer for subjects with parenchymal or pleural involvement.

Benign thyroid cysts often recur after aspiration; the effectiveness of tetracycline instillation in the case of recurrence has been questioned. We, therefore, tested the efficacy of percutaneous ethanol injection in 20 patients with "pure" cyst relapsing after aspiration. After evacuation, 95% ethanol was instilled under sonographic guidance and re-aspirated 5 min later. The procedure was performed twice for larger cysts. Follow-up studies were carried out after 1, 3, 6, and 12 months. In case of recurrence at 1 month, patients (n = 5) were submitted to a second session. A slight burning sensation was the only adverse effect. No recurrences were observed at 3 and 6 month follow-up; only one patient with recurrence after 1 month had relapsed at 12 months. A significant shrinkage (P < 0.0001 vs. pretreatment) was observed in all other cases at 12 months; cysts were not detectable in seven patients (35%). No significant variations in thyroid hormone levels were detected during treatment or follow-up. Serum thyroglobulin levels markedly increased 3 h after ethanol injection. One month after treatment, thyroglobulin returned to pretreatment levels, thus excluding progressive thyroid damage. Percutaneous ethanol injection may prove a safe and effective tool for the therapy of thyroid cysts.

Background: Levothyroxine has often been given to patients operated on for nodular goiter to prevent recurrence. The rationale is that suppression of thyroid-stimulating hormone (TSH), considered to be the main growth factor in this disease, can be obtained by administration of levothyroxine., Methods: Sixty patients undergoing operation for nontoxic nodular goiter were randomized in two groups: (1) thirty-two were administered levothyroxine at substitutive dosage (100 micrograms) or placebo and (2) twenty-eight were given levothyroxine at suppressive dosage (2.2 to 3 micrograms/kg/day). Levels of thyroid hormones and TSH were evaluated every 6 months. Recurrences detected by echography were then considered., Results: After a 3-year follow-up we observed 25 of 32 recurrences in group 1 and 6 of 28 in group 2 (p < 0.005). Subjects with endemic goiter problems responded better to therapy. Patients with a multinodular goiter responded better than patients with a uninodular goiter. No difference was found regarding the type of surgical treatment (subtotal thyroidectomy vs lobectomy)., Conclusions: The results confirmed suppressive therapy as actually being effective in preventing recurrences at least in iodine-deficient regions like Italy. Thus for these patients it may be suggested as a prophylactic treatment after operation.

C cells of the thyroid probably exert a paracrine control on follicular cells through secretion of peptides such as calcitonin and somatostatin. The aim of the present study was to investigate the expression of different peptides produced by C cells in rat thyroid and in the different morphological and pathological conditions of the human thyroid. Therefore we employed the immunohistochemical double-staining method using anti-calcitonin and anti-somatostatin antibodies. The results of this study show the presence of C cells containing calcitonin and C cells containing somatostatin exclusively in the rat and the human thyroid. This distinction with prevalence of one peptide on the other is maintained in the different morphological and pathological conditions of the human thyroid.

Frank hypothyroidism is known to induce neurological and mental dysfunction. The aim of this study was to assess selected neuropsychological and behavioral features by means of standardized tests in a group of 14 patients with subclinical hypothyroidism who were free from neuropsychological complaints and to evaluate the possible effects of L-thyroxine treatment on their performance. Patients were submitted to the Crown and Crisp Experiential Index and to the Wechsler Memory Scale; their ratings on the neurobehavioral tests and their thyroid hormone profile were compared to those of a control group of 50 age- and sex-matched subjects. Comparison was also carried out between pretreatment ratings and those obtained following a 6-month L-thyroxine course (0.1-0.15 mg/day). The Wechsler Memory Scale ratings showed a significant impairment in patients' memory-related abilities [memory quotient (MQ) = 89.1 +/- 2.9; P = 0.002 (patients versus controls)]; the Crown and Crisp Experiential Index ratings demonstrated moderate differences between untreated patients and controls with respect to hysteria (P = 0.03), anxiety (P = 0.05), somatic complaints (P = 0.0005), and depressive features (P = 0.002) scales; the total score was also significantly higher (42.0 +/- 3.8; P = 0.005). After L-thyroxine treatment the patients' performances showed an improvement in memory skills, as evaluated by the Wechsler Memory Scale [MQ = 99.9 +/- 4.0; P = 0.002 (treated versus untreated)]; somatic complaints (P = 0.02) and obsessionality (P = 0.04) ratings and the Crown and Crisp Experiential Index total score (P = 0.04) significantly decreased with respect to untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Concentration of C cells in the thyroid of rats treated with Mercaptoimidazole or Levo-thyroxine. The aim of the present study was to elucidate the possible functional relationship between follicular and parafollicular cells of the thyroid gland; therefore we have investigated the behaviour of calcitonin producing cells and serum calcitonin concentration in rats both in resting and hyperstimulation conditions of follicular cells. Our results showed that with regard to follicular mass the concentration of the C cells was reduced in the two groups of rats treated compared to control rats. C cell concentration decrease was associated with reduced serum calcitonin concentration. In conclusion C cell activity is independent of TSH and thyroid hormones circulating levels.

Thyroid adenoma is commonly associated with surgery and radiometabolic treatment; recently, according to previous successful reports, percutaneous ethanol injection therapy under sonographic guidance, has been introduced as an alternative. This technique has already been favourably used in the treatment of focal lesions, such as liver cancer and hyperparathyroidism. In our experience, we have treated with such therapy 69 patients affected by thyroid adenoma (55 females, 14 males; 28 pretoxic, 41 toxic). Ethanol (0.5-2.8 mL/mL nodular tissue) was injected, under sonographic guidance, in 4-9 sessions (1 weekly). Thyroid hormone profile was assessed during treatment and at 3 and 6 months follow-up. Apart from local transient pain in 21% sessions, two cases of pyrexia (38.5 degrees-1 day) and 3 cases of transient dysphonia, no relevant adverse effects were observed. A slight thyroid hormone increase was seen in both groups immediately following treatment. Six months after therapy a biochemical and clinical remission of hyperthyroidism was observed in 33 out of 41 toxic patients (80%); a significant increase of TSH levels was seen in both groups (p < 0.001). With follow-up, significant volume shrinkage (70-80% volume reduction--p < 0.0001) as well as structural alterations of the nodule, were consistently recorded at sonography, in both groups; a linear relationship (p < 0.0001) between pretreatment volume and volume reduction was found. At scintiscan functional activity of extranodular parenchyma was found in 75% of patients affected by pretoxic adenoma and in 63.1% of patients with toxic adenoma. These data confirm that percutaneous ethanol injection therapy is effective in obtaining functional ablation and in inducing remission of hyperthyroidism, when present; so it represents a valid and safe alternative to standard therapeutic tools of thyroid adenoma.

A 59 year old man presenting fever, serum hyponatremia and hypoosmolality in association with hyperosmotic urine was hospitalized in our unit in February 1988. We demonstrated evidence of systemic sarcoidosis and inappropriate secretion of antidiuretic hormone (ADH). The patient was treated with corticosteroid therapy for a period of about 1 year, with regression of signs of the inappropriate vasopressin secretion as well as the symptomatology related to systemic sarcoidosis. This study identified systemic sarcoidosis as a definite cause of "syndrome of inappropriate ADH secretion".

Three patients affected with Graves' ophthalmopathy and pretibial myxoedema have been treated with high dose intravenous immunoglobulins. We have observed in all patients clinical improvement of pretibial myxoedema and a parallel reduction or negativization of the titre of circulating thyroglobulin, microsomal, TSH receptor autoantibodies and of non organ-specific antibodies (antinuclear, anti smooth muscle cells and antimitochondrial autoantibodies). In conclusion the results of this study suggest that intravenous immunoglobulin are effective in the treatment of pretibial myxoedema and probably act by an immunomodulation of autoimmune phenomena.

We report the effect of "intravenous gamma-globulin treatment" (IVIG) in a patient with autoimmune polyglandular syndrome type II, with circulating organ specific autoantibodies, preclinical hypothyroidism, amenorrhea and Addison syndrome. During IVIG treatment we observed a normalization of thyroid function, the appearance of some non ovulatory menses, reduction of thyroglobulin, thyroidal microsomal, anti-parietal cell, adrenal and ovary antibodies. These data confirm that intravenous immunoglobulin may represent a new tool for treatment of autoimmune disorders and show, for the first time, an immunosuppressive effect of intravenous gammaglobulin treatment in immunological phenomena direct against ovary, adrenal and gastric mucosa.

The aim of this study was to evaluate the variations of thyroid autoantibodies titre in a group of 15 patients affected with "Graves' disease" (G. D.) during the treatment with antithyroid drug (ATD) and "high dose intravenous immunoglobulin" (IVIG) for "Graves' ophthalmopathy". Before the starting of treatment thyroglobulin antibodies (TgAb) were positive in 10/15 patients, microsomal antibodies (MAb) were positive in 13/15 patients and TRAb were positive in 5/9 patients. At the end of treatment TgAb titre was decreased or negative in 7/10 patients, MAb titre was decreased or negative in 7/13 patients, TRAb titre was diminished or negativized in 5/5 patients. Anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were positive in 3/15 and 3/15 patients before the treatment and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA)m anti-mitochondrial antibodies (AMA) and rheumatoid factors were negative in all the patients. Also in the 3 patients not treated with ATD we have observed a reduction or a negativization of circulating thyroid autoantibodies. In conclusion these data suggest that the reduction of thyroid and non organ specific autoantibodies might be due to a stable immunosuppressive action of IVIG treatment in patients with Graves' disease.

Recent reports of transmission by intravenous gamma-globulin preparations of A, B, C and non-A non-B hepatitis (NANBH), including several cases that progressed to severe liver damage and death, have raised concerns about the safety of intravenous gamma-globulins. To assess this issue 15 patients treated with high-dose "intravenous immunoglobulin" (IVIG) for Graves' Ophthalmopathy had serial determination of glutamic pyruvic transaminase (GPT), glutamic oxalacetic transaminase (GOT), gamma glutamyltranspeptidase (gamma-GT), alkaline phosphatase and bilirubin that were performed regularly at interval of 3 weeks during IVIG treatment and 6 months after the end of the treatment. Hepatitis A, B, C and HIV markers were determined before, during and 6 months after the end of the treatment. The standard dosage was 400 mg per Kg body weight IVIG (3 cycles of 5 days and 12 of 1 day, every 21 days). Transient minor elevations were observed for GPT, for GOT, for gamma-GT and alkaline phosphatase. None of the elevations were considered indicative of NANBH or of any chronic hepatic disease. Transient presence of hepatitis A, B and C antibodies were observed in 6 patients. All patients remained negative for hepatitis B antigens throughout the study. HIV antibodies resulted always negative in all patients. In conclusion this study suggests the hepatitis and HIV safety of IVIG.

We have evaluated the variations of thyroid function, of thyroid autoantibodies titer, of non-organ specific autoantibodies and of other autoimmunity indices in 3 patients affected with Hashimoto's thyroiditis treated with "high dose intravenous gammaglobulin" (IVIG) (400 mg/Kg/day for 3 cycles of 5 days and subsequently 9-12 cycles of 1 day every 21 days). Before the starting of IVIG treatment patient 1 presented clinically evident hypothyroidism while patients 2 and 3 presented a preclinical form of hypothyroidism. At the end of IVIG treatment patients presented no variation of thyroid function, while patients 2 and 3 presented a normalization of T3, T4 and TSH circulating levels. Before the starting of IVIG treatment thyroglobulin antibodies (TgAb) were positive in 3/3 patients, microsomal antibodies (MAb) were positive in 3/3 patients adt TRAb were positive in 2/3 patients and MAb titre was decreased or negative in 0/3 patients. At the end of IVIG treatment Tg Ab titre was decreased or negative in 2/3 patients and MAb titre was decreased or negative in 2/3 patients. Anti-nuclear antibodies (ANA) 1/3 patients before the titre and in all these we observed a reduction or negativization of circulating titre during IVIG treatment. Anti-extractable nuclear antigen (ENA), anti-mitochondrial antibodies (AMA), C3, C4, CH50 and rheumatoid factors were negative or in the normal range in all the patients. In conclusion these data suggest that IVIG is effective in the treatment of preclinical hypothyroidism in patients with Hashimoto's thyroiditis and determine a stable immunosuppressive action on circulating thyroid and non organ specific autoantibodies.

Crohn's disease with acute abdomen in pregnancy is described. The Authors evaluate Crohn's disease together with the diagnostic, prognostic and therapeutic problems and relationships between this disease and pregnancy. They conclude as underlining the rarity of Crohn's disease beginning in pregnancy and so the importance of symptoms related to this disease in fertile age woman to make diagnosis and therapy before pregnancy.

Objective: We have evaluated the efficacy of percutaneous ethanol injection as an alternative to surgery and iodine-131 treatment in solitary autonomous thyroid adenoma., Design: Percutaneous ethanol injection (0.5-2.8 ml ethanol/ml nodular tissue) was performed under sonographic guidance in 3-5 (1-2 weekly) sessions; a 7.5 MHz linear real-time scanner (Toshiba, mod. 32B) was used for sonographic studies. The thyroid hormone profile was assessed during treatment and for the next 6 months., Patients: Fifty-six patients (40 females, 16 males, mean age 46 +/- SD 9 years; 30 pretoxic, 26 toxic) were included in the study: their pretreatment technetium-99 m thyroid scan showed a single hot nodule with total suppression of extranodular tissue in 45 and near-total suppression in 11., Measurements: Thyroid hormones, antithyroglobulin and antiperoxidase antibodies were measured by specific radioimmunoassay, while thyrotrophin was evaluated by ultrasensitive immunoradiometric assay., Results: Apart from a case of transient pyrexia, no relevant adverse effects were observed. A slight thyroid hormone increase was seen in both groups immediately following a treatment. Six months after therapy a biochemical and clinical remission of hyperthyroidism was observed in 18 out of 22 toxic patients (81.8%); a significant increase of TSH levels was seen in both groups (P less than 0.01). With follow-up, significant volume shrinkage (P less than 0.001) as well as structural alterations of the nodule were consistently recorded at sonography; a linear relationship (r = 0.98; P less than 0.0001) between pretreatment volume and volume reduction was found. At scintiscan, functional activity of extranodular parenchyma was found in 40 out of 56 patients (71.4%), 16/26 (61.5%) in the hyperthyroid group, 24/30 (80.0%) in the pretoxic group., Conclusions: These data confirm that percutaneous ethanol injection is effective in obtaining functional ablation and in inducing remission of hyperthyroidism, when present; adverse effects seem infrequent.

A group of 248 asymptomatic postmenopausal patients was evaluated using transvaginal echography. Thirty-five patients with endometrial echopatterns which were larger than 8 mm and/or irregular then underwent hysteroscopy and endometrial biopsy. Results show that 31.4% of cases in which there was a thickening of the endometrial echopattern correspond to the presence of polyp, myoma, synechia with atrophic endometrium. In conclusion, the Authors affirm the inappropriateness of the term "endometrial echopattern" in menopause, since this term should be reserved to describe the typical appearance of the endometrium during the reproductive phase. They stress that ultrasonography can reveal anomalies of the internal echostructure of the womb but that further tests (e.g. hysteroscopy, biopsy) are required to diagnose their nature.

Three patients with the carcinoid syndrome received intravenous somatostatin (3.5 micrograms/min) for one day; intravenous salmon calcitonin (8 IU/hr) for one day; subcutaneous salmon calcitonin (100 IU three times daily) for ten days; and subcutaneous octreotide (150 micrograms three times daily) for ten days. Octreotide (SMS-201.995) is a stable analogue of somatostatin. There was a five-day washout period between each treatment. During each of these treatments, reductions in the numbers of daily flushes and bowel movements, stool weight, and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were observed. Relief of cramping abdominal pains was also reported. Patients 1 and 3 chose to continue receiving the subcutaneous calcitonin and patient 2 chose the octreotide. Patient 1 (aged 67 years) reported relief of symptoms for five months until she developed an intestinal obstruction as a result of tumor infiltration. Patient 3 (aged 67 years) has received the calcitonin for about 16 months with relief of symptoms and reduced urinary 5-HIAA levels. Patient 2 (aged 57 years) has continued octreotide treatment for one year and reports relief of symptoms.

We have evaluated the efficacy of high-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy, and have carried out a prospective randomized clinical trial, including a single-blind evaluation, whereby 14 patients were assigned to two different treatment groups: 7 patients were treated with intravenous immunoglobulin and orbital radiotherapy (Group 1) and 7 patients were given intravenous immunoglobulin alone (Group 2). The results of the intravenous immunoglobulin treatment were also compared with those obtained in a Historical Control Group (12 patients) treated with systemic methylprednisolone and orbital irradiation. Degree of ocular involvement and response to treatment were assessed by ophthalmopathy index. The mean initial and final ophthalmopathy index showed no significant difference among the three groups. Comparison between the mean initial and final ophthalmopathy index showed a statistically significant reduction (p less than 0.005) in all three groups, the observed changes being confirmed by orbital computerized tomography in Groups 1 and 2. Corticosteroid treatment was associated with major and minor side effects, while no important adverse reactions were observed during intravenous immunoglobulin treatment. Even considering our results as preliminary, we conclude that intravenous immunoglobulin treatment is effective and safe in improving Graves' ophthalmopathy.

The most frequently used medical treatment of Graves' ophthalmopathy is the combination of orbital irradiation and systemic corticosteroid. In this study the effectiveness of "high dose intravenous immunoglobulin" (IVIG) in Graves' ophthalmopathy treatment is explored. 11 patients were treated with orbital radiotherapy combined with systemic corticosteroid (Group 1), while 10 patients were treated with the combination of orbital irradiation and IVIG (Group 2). The therapeutic effect was assessed by an ophthalmopathy index based on the American Thyroid Association, classification of ocular changes of Graves' ophthalmopathy. All signs and symptoms of endocrine ophthalmopathy improved significantly in both groups. The mean ophthalmopathy index decreased from 7.0 +/- 1.3 to 3.4 +/- 1.5 in Group 1, and from 7.0 +/- 1.8 to 3.0 +/- 2.1 in Group 2. Statistical analysis showed no significant difference between Group 1 and 2 mean initial and final ophthalmopathy index, and a significant difference between initial and final ophthalmopathy index both in Group 1 and 2. While side effects were present in Group 1 treated with systemic corticosteroid, no side effect was observed in patients treated with IVIG. These preliminary results suggest that IVIG is safe and effective in the treatment of Graves' ophthalmopathy.

Subclinical hypothyroidism in characterized by elevated TSH levels in the face of normal thyroid hormone concentrations. The purpose of this study was to evaluate whether these subjects show alterations of neuropsychological and behavioural features and of myocardial contractility as patients with overt hypothyroidism do. We evaluated in 14 subjects the hormonal profile (total and free T3 and T4, TSH), memory ability (Wechsler Memory Scale), behavioural reactivity (Crown & Crisp Experimental Index) and the pre-ejection period (isometric systole). We found an evident impairment of some cognitive functions correlated to memory and a behavioural alteration, perhaps secondary to the disease state, and moreover an early defect of myocardial contractility, represented by prolonged pre-ejection period. These results suggest that these patients should be treated with adequate doses of L-Thyroxine, like in overt hypothyroidism.

A case of sonographic diagnosis of single umbilical artery associated with hypoplastic left heart syndrome and left renal agenesis is reported. Umbilical artery Doppler waveforms are presented and discussed for the first time.

We studied the effects of long-term (30 days) refracted daily intramuscular administration of 4 mg TRH tartrate (TRH-T) on the pituitary-thyroid axis in 20 euthyroid patients affected by cerebrovascular disease (CVD). All subjects were assayed for T4, T3, FT4, FT3, TSH and TBG plasma levels before treatment (D0), after 15 and 30 treatment days (D15, D30), and after a 15-day washout (D45). In addition, TSH response to 200 micrograms intravenous TRH was assessed at D0, D30 and D45. We observed a significant increase in T4, FT4 and FT3 levels in the face of decreased TSH concentrations. A blunted TSH response to TRH bolus persisted at D30. These data demonstrate that the down-regulation mechanism may be partially overcome in vivo when thyrotrophs are chronically exposed to pharmacological TRH-T doses and that TSH pattern is mainly due to the negative feedback of thyroid hormones, even though pituitary TSH reserves may become depleted. Furthermore, prolonged TRH-T administration does not produce hyperthyroidism in euthyroid CVD patients.

The fast-moving field of photodynamic therapy (PDT) has provided fresh opportunities to expand the potential of metallodrugs to combat cancers in a light-controlled manner. As such, in the present study, a series of cyclometalated Ir(III) complexes modified with a tetrazine functional group (namely, Ir-ppy-Tz, Ir-pbt-Tz, and Ir-dfppy-Tz) are developed as potential two-photon photodynamic anticancer agents. These complexes target mitochondria but exhibit low toxicity towards HLF primary lung fibroblast normal cells in the dark. When receiving a low-dose one- or two-photon PDT, they become highly potent towards A549 lung cancer cells (with IC50 values ranging from 24.0 nM to 96.0 nM) through the generation of reactive oxygen species (ROS) to induce mitochondrial damage and subsequent apoptosis. Our results indicated that the incorporation of tetrazine with cyclometalated Ir(III) matrices would increase the singlet oxygen (1O2) quantum yield (ΦΔ) and, meanwhile, enable a type I PDT mechanism. Ir-pbt-Tz, with the largest two-photon absorption (TPA) cross-section (σ2 = 102 GM), shows great promise in serving as a two-photon PDT agent for phototherapy. [ABSTRACT FROM AUTHOR]

Inositols have demonstrated a role in cancer prevention and treatment in many kinds of neoplasms. Their molecular mechanisms vary from the regulation of survival and proliferative pathways to the modulation of immunity and oxidative stress. The dysregulation of many pathways and mechanisms regulated by inositols has been demonstrated in endocrine and neuroendocrine tumors but the role of inositol supplementation in this context has not been clarified. The aim of this review is to summarize the molecular basis of the possible role of inositols in endocrine and neuroendocrine tumors, proposing it as an adjuvant therapy. [ABSTRACT FROM AUTHOR]