Thyroid hormones act as mitogenic and pro survival factors in rat ovarian follicles.

PURPOSE: Thyroid disorders are clinically associated with impaired fertility in women, and these abnormalities can be improved by restoring the euthyroid state. The exact mechanisms of thyroid effect on female fertility are not well known; however, it is conceivable that thyroid hormones (THs) might act on ovarian physiology via receptors in granulosa cells. This work is aimed at evaluating the effects of THs on non-tumoral granulosa cells and follicles. METHODS: Freshly isolated rat ovarian follicles and granulosa cells were exposed to T3 or T4 (THs). Cell growth and viability were evaluated by cell counting and the MTT assay, respectively, follicle growth was evaluated by volume measurements. Apoptosis was evaluated by the TUNEL assay and active Caspase 3 staining. rGROV cells were exposed to T3, and apoptosis was induced by serum deprivation. Bcl2, Bcl-2-associated X protein (BAX), Akt and pAkt expression were evaluated by western blot. RESULTS: T3 induced a 40% increase in follicle volume (after 7 days). This increase was presumably due to the observed decrease (33%) in the apoptotic rate of the granulosa cell population. Both T3 and T4 caused a dose-dependent increase in rat granulosa cell number and viability. In addition, THs decreased the cell apoptotic rate in a dose-dependent manner. In both conditions, T3 appeared to be more efficient. In rGROV cells, 100 nM T3 induced cell growth and, in the absence of growth factors, reduced cell apoptosis by 40%, downregulating Caspase 3 and BAX. This effect was associated with an increase in pAkt levels. The involvement of the PI3 K pathway was confirmed by the ability of the PI3 K specific inhibitor (LY-294,002) to abolish T3 pro-survival action. CONCLUSIONS: THs influence cell survival of ovarian granulosa cells. This effect likely contributes to the TH-induced follicle volume increase.

What is the role of contrast-enhanced ultrasound in the evaluation of the endoleak of aortic endoprostheses? A comparison between CEUS and CT on a widespread scale.

OBJECTIVE: To evaluate the accuracy of contrast-enhanced ultrasound (CEUS) in comparison to CT angiography (CTA) to identify and classify endoleaks following abdominal aortic aneurism repair with endoprosthesis. MATERIALS AND METHODS: A retrospective analysis of 181 patients treated with EVAR, from September 2009 to September 2014, was performed. Patients were evaluated with CEUS, CTA and angiography in the cases requiring treatment. Sac diameter, sac integrity, identification and classification of endoleaks were taken into consideration. Sensitivity, specificity, accuracy and negative predictive values were considered for each modality of endoleak identification. RESULTS: Forty-two endoleaks (23.2%; type II: 39 cases, type III: 3 cases) were documented. Sensitivity and specificity of CEUS and CT were, respectively, 97.6 and 90.5, 100 and 100%. In two cases, CEUS was able to better classify endoleaks compared to CT. CONCLUSIONS: CEUS accuracy to identify endoleaks following EVAR is similar to CT. CEUS should be considered as an effective modality for the long-term surveillance of EVAR because of its capability to correctly classify endoleaks with no ionizing radiation exposure.

Role of water in chromosome spreading and swelling induced by acetic acid treatment: a FTIR spectroscopy study.

The so called chromosome preparation is a procedure consisting of three strictly connected stages that enables to obtain chromosomes of quality suitable for cytogenetic analysis. Interestingly, experimental evidence strongly suggested that chromosome spreading and swelling (key processes that allow their counting and detailed structural analysis) are induced in the last fixative-evaporation stage by the interaction, mediated by acetic acid, between water from the environmental humidity, and the cytoplasmic matrix and the chromatin. However, since a considerable variation in the quality of chromosome preparations is observed, strongly depending on the environmental conditions in which the procedure takes place, a better comprehension of the mechanisms underlying chromosome preparation is required. To this aim, here we analysed intact lymphocytes before and at each stage of the chromosome preparation protocol by Fourier transform infrared (FTIR) spectroscopy, a technique widely used for the study not only of isolated biomolecules, but also of complex biological systems, such as whole cells. Interestingly, we found that the chromosome preparation protocol induces significant structural changes of cell proteins and DNA, in particular due to the interaction with acetic acid. Moreover, noteworthy, through the monitoring of changes in the water combination band between 2300 and 1800 cm-1, we provided evidence at molecular level of the crucial role of the bound water to the cytoplasmic matrix and to the chromatin in determining the chromosome spreading and swelling. Our FTIR results, therefore, underline the need to perform the last fixative-evaporation stage in standardized and optimized temperature and relative humidity conditions, thus providing chromosomes of high quality for the cytogenetic analysis that would lead in this way to more reliable results.

Clinical relevance of thyroid-stimulating autoantibodies in pediatric graves' disease-a multicenter study.

CONTEXT AND OBJECTIVE: The incidence of TSH receptor (TSHR) stimulating autoantibodies (TSAbs) in pediatric Graves' disease (GD) is controversial. This large, multicenter study evaluated the clinical relevance of TSAbs in children with GD both with Graves' orbitopathy (GO) and without orbital disease. DESIGN: We conducted a cross-sectional retrospective study. SETTING: Sera were collected in seven American and European academic referral centers and evaluated in a central laboratory. PATIENTS AND SAMPLES: A total of 422 serum samples from 157 children with GD, 101 control individuals with other thyroid and nonthyroid autoimmune diseases, and 50 healthy children were studied. MAIN OUTCOME MEASURES: TSAbs were measured using a novel, chimeric TSHR bioassay and a cAMP response element-dependent luciferase. TSH binding-inhibitory Ig (TBII) and parameters of thyroid function were also determined. RESULTS: In 82 untreated children with GD, sensitivity, specificity, and positive and negative predictive values for TSAb and TBII were: 100 and 92.68% (P = .031), 100 and 100%, 100 and 100%, and 100 and 96.15%, respectively. TSAb and TBII were present in 147 (94%) and 138 (87.9%) of the 157 children with GD (P < .039), respectively; and in 247 (94%) and 233 (89%) of the 263 samples from this group (P < .0075), respectively. In children with GD and GO, TSAb and TBII were noted in 100 and 96% (P < .001), respectively. Hyperthyroid children with GD and GO showed markedly higher TSAb levels compared to those with thyroidal GD only (P < .0001). No significant differences were noted for TBII between the two groups. After a 3-year (median) medical treatment, the decrease of TSAb levels was 69% in GD vs 20% in GD and GO (P < .001). All 31 samples of euthyroid children with GO were TSAb positive; in contrast, only 24 were TBII positive (P = .016). All children with Hashimoto's thyroiditis, nonautoimmune hyperthyroidism, type 1 diabetes, and juvenile arthritis and the healthy controls were TSAb and TBII negative. CONCLUSIONS: Serum TSAb level is a sensitive, specific, and reproducible biomarker for pediatric GD and correlates well with disease severity and extrathyroidal manifestations.

Upper gastrointestinal endoscopic findings and prevalence of Helicobacter pylori infection among adult patients with dyspepsia in northern Tanzania.

Dyspepsia is a common presenting complaint of various upper gastrointestinal disorders. The symptoms of causes of dyspepsia often overlap and this makes etiological diagnosis difficult. Endoscopy is the ideal procedure for identifying organic diseases of the foregut. Helicobacter pylori infection is associated with various upper gastrointestinal pathologies. A cross-sectional study was conducted to determine endoscopic findings and H. pylori status in two hundred and eight consecutive dyspeptic adult patients between June 2009 and April 2010 at Kilimanjaro Christian medical Centre, a referral and teaching hospital in northern Tanzania. The most commonly identified endoscopic findings were gastritis (61.10%), Gastroesophageal reflux disease (GERD) (57%), and Peptic ulcer disease (PUD) (24.1%). Gastric cancer was identified in 6.7% of patients and all of them were aged 40 years and above (p = 0.00). H. pylori infection was detected in 65% (n = 130) of patients. H. pylori infection was present in 57% (n = 24) of patients who were tested within six months after eradication therapy. Gastritis and duodenal ulcer were statistically significantly associated with H. pylori (p < 0.001). No association was found between GERD and H. pylori infection (p > 0.05). Gastritis, GERD, and PUD are the leading causes of dyspepsia. H. pylori infection is present in significant proportion of dyspeptic patients. Patients with Gastritis and PUD should undergo empirical eradication therapy if a confirmatory test is not available. Patients with dyspepsia who are over 40 years of age should undergo Endoscopy (EGD) for initial work up. Study on antimicrobial susceptibility pattern of H. pylori is recommended to guide choices for evidence based treatment option.

Prospective comparative evaluation of quantitative-elastosonography (Q-elastography) and contrast-enhanced ultrasound for the evaluation of thyroid nodules: preliminary experience.

PURPOSE: To assess the effectiveness of semiquantitative elastosonography (Q-elastography) compared with contrast-enhanced ultrasound (CEUS) in differentiating the nature of thyroid nodules. METHODS AND MATERIALS: Forty-eight consecutive patients (35 males, 13 females, range: 34-69 years, mean: 49.4 years), candidate to surgery, previously detected at color-Doppler ultrasound (CDUS), were prospectively examined with elastosonography with dedicated semiquantitative software (Q-Elastography, Toshiba XG) and CEUS (Technos Mylab 70 Gold X, and Toshiba XG) before surgery. CEUS and elastosonography were evaluated by two investigators in consensus. Comparison between the CEUS pattern and elastonographic strain ratio observed and expected frequencies for the diagnoses was evaluated with χ(2) test or with Fisher exact test. RESULTS: Fifty-three nodules (19 papillary carcinoma, 32 hyperplasia, and 2 follicular adenoma) in 48 patients were available for analysis. Regarding echogenicity score, sensitivity, specificity, PPV and NPV of conventional US were 81%, 50%, 56%, 77%; according to Q-elastography, sensitivity, specificity, PPV and NPV were 95%, 88%, 97% and 91% respectively; whereas concerning CEUS, sensitivity specificity PPV and NPV were 79%, 91%, 83% and 89% respectively. Both CEUS and Q-elastography were more specific than US (p<0.01), with not statistical significant difference with regard to sensitivity. CONCLUSIONS: The results of the present study suggest that Q-elastography is a valuable tool in the characterization of thyroid nodules and it seems to be more sensitive than CEUS.

Upper Gastrointestinal Endoscopic Findings and Prevalence of Helicobacter Pylori Check for this Species in other Resources Infection among Adult Patients with Dyspepsia in Northern Tanzania

Dyspepsia is a common presenting complaint of various upper gastrointestinal disorders. The symptoms of causes of dyspepsia often overlap and this makes etiological diagnosis difficult. Endoscopy is the ideal procedure for identifying organic diseases of the foregut. Helicobacter pylori infection is associated with various upper gastrointestinal pathologies. A cross-sectional study was conducted to determine endoscopic findings and H. pylori status in two hundred and eight consecutive dyspeptic adult patients between June 2009 and April 2010 at Kilimanjaro Christian medical Centre; a referral and teaching hospital in northern Tanzania. The most commonly identified endoscopic findings were gastritis (61.10); Gastroesophageal reflux disease (GERD) (57); and Peptic ulcer disease (PUD) (24.1). Gastric cancer was identified in 6.7 of patients and all of them were aged 40 years and above (p=0.00). H. pylori infection was detected in 65 (n=130) of patients. H. pylori infection was present in 57 (n=24) of patients who were tested within six months after eradication therapy. Gastritis and duodenal ulcer were statistically significantly associated with H. pylori (p0.001). No association was found between GERD and H. pylori infection (p0.05). Gastritis; GERD; and PUD are the leading causes of dyspepsia. H. pylori infection is present in significant proportion of dyspeptic patients. Patients with Gastritis and PUD should undergo empirical eradication therapy if a confirmatory test is not available. Patients with dyspepsia who are over 40 years of age should undergo Endoscopy (EGD) for initial work up. Study on antimicrobial susceptibility pattern of H. pylori is recommended to guide choices for evidence based treatment option

Varicocele: Ultrasonographic assessment in daily clinical practice.

INTRODUCTION: Varicoceles are abnormal dilatations of the pampiniform venous plexus. They are classified as primary or secondary, depending on their cause, and staged clinically on the basis of their extension and on the presence or the absence of spontaneous or induced reversal of blood flow. MATERIALS AND METHODS: We examined 95 patients (age range: 3-77 years) using Color Doppler ultrasound with settings optimized for the study of slow flow. All patients found to have varicoceles underwent ultrasonographic assessment of the kidneys and retroperitoneum. Findings were classified with a simplified version of the Sarteschi system. RESULTS: 41 (43.1%) of the patients were found to have varicoceles, which were classified as grade 1 in 11 cases, grade 2 in 13, grade 3 in 10, and grade 4 in 7 according to the simplified Sarteschi classification. DISCUSSION: Our results are with those reported in the literature. They confirm that varicoceles are a frequent finding and ultrasonography is currently the best imaging technique for its diagnosis and also for the post-surgery follow-up.

Precocious puberty in two girls with Chiari I malformation: a contribution to a larger use of brain MRI in the diagnosis of central precocious puberty.

Up to now Chiari malformation has been reported only in four subjects with precocious puberty, with a prevalence among boys. This article describes the case of two female children affected by progressive precocious puberty detected through brain magnetic resonance imaging (MRI). Brain imaging, even without neurological signs, can identify patients at risk of developing subsequently severe neurological symptoms. Our observation supports the usefulness of brain MRI both in males and females, even when no symptoms are present, to identify and detect high risk cases. However, there is no consensus in Literature in performing MRI in all the patients of both sexes with central precocious puberty, due to its high costs.

Is pattern III as evidenced by US color-Doppler useful in predicting thyroid nodule malignancy? Large-scale retrospective analysis.

OBJECTIVE: To evaluate whether pattern III of color Doppler Ultra-sound may identify malignant nodules. MATERIALS AND METHODS: We have retrospectively analyzed data pertaining to 1090 patients of both genders (230 males, 860 females), with an average age of 53 years (min 17 years, max 81 years), who underwent thyroidectomy in Department of Surgical Sciences of Sapienza University of Rome since January 2003 through June 2009. We correlated color-Doppler characteristics and histological features through statistical analysis so as to verify statistical correlation between them. RESULTS: Our study showed that 164/273 (60.1%) patients with malignant disease were associated with vascularization pattern III. Regarding benign disease, 152/268 (56.7%) patients showed a pattern of vascularization 3 at ultrasonography. The statistical analysis was not able to show any correlation between pattern III and malignancy. CONCLUSION: Pattern III cannot be used to predict malignancy with confidence, and FNA is still mandatory to rule out the nature of the nodule.

A case of subfascial lipoma in the lateral space of neck: US and CT findings.

Lipomas in the head and neck region usually occur in the immediate subcutaneous tissue. They are extremely rare under the muscular band of neck. We present a case of a 53-year-old woman with a subfascial lipoma located in the anterior lateral space of neck. The diagnosis of the lesion was reached by clinical examination and confirmed by ultrasonography (US) and computed tomography (CT) imaging. The lesion with surrounding capsule formation and lipofibromatous changes underwent open surgery.

Vascular leiomyoma presenting as medial joint line pain of the knee.

Vascular leiomyoma or angioleiomyoma is a rare benign solitary smooth muscle tumor that occurs mostly in the extremities. Most of these tumors are composed of venous vessels, but in some reports small arteries have been detected in the tumors.We present a rare case of a 60-year-old man with a subcutaneous vascular leiomyoma of the right knee. Clinical findings, ultrasound (US), magnetic resonance (MR), and histopathologic features are reported, and the literature is reviewed. The knowledge of specific imaging findings allows to include vascular leiomyoma in the differential diagnosis of lower extremity subcutaneous masses and to achieve an early accurate diagnosis.

Childhood Graves' ophthalmopathy: results of a European questionnaire study.

OBJECTIVE: Evaluation of the frequency of Graves' ophthalmopathy (GO) and its management in children and adolescents up to 18 years old with Graves' hyperthyroidism. STUDY DESIGN: This was a questionnaire study (QS) among members of the European Thyroid Association and the European Society for Paediatric Endocrinology. Approximately 300 QS were sent to members with electronic addresses and 110 QS were returned from 25 countries: 52 respondents said they had no experience with Graves' disease in this age group, but 67 respondents (23 paediatric and 44 adult endocrinologists) completed the QS. RESULTS: Out of 1963 patients with juvenile Graves' hyperthyroidism seen by respondents in the last 10 years, 641 (33%) had GO; about one-third of GO cases were < or =10 years old, and two-thirds were 11-18 years old. The prevalences of GO among juvenile Graves' hyperthyroidism were 36.6, 27.3 and 25.9% in countries in which the smoking prevalence among teenagers was > or =25, 20-25 and <20% respectively (P < 0.0001 by chi(2) test). When confronted with the standard case of a 13-year-old girl with Graves' hyperthyroidism and moderately severe active GO, the diagnostic approach included on average 4.9 biochemical tests (TSH, free thyroxine (FT(4)) and TSH.R-Ab, 100-88% of respondents) and 2.4 specific investigations (thyroid ultrasound by 69%, orthopsy/visual fields/visual acuity by 64% and orbital magnetic resonance imaging or computed tomography by 63%). Antithyroid drugs were the treatment of choice for 94% of respondents; 70% recommended a wait-and-see policy and 28% corticosteroids for the co-existing GO. In variants of the standard case, a younger age did not affect therapeutic approach very much. Recurrent hyperthyroidism would still be treated with antithyroid drugs by 66%, and with (131)I by 25%. Worsening of GO or active GO when euthyroid would convince about two-thirds of respondents to initiate treatment of GO, preferably with steroids. CONCLUSION: GO occurs in 33% of patients with juvenile Graves' hyperthyroidism; its prevalence is higher in countries with a higher prevalence of smoking among teenagers. The diagnostic approach to the standard case of a 13-year-old with Graves' hyperthyroidism and moderately severe active GO involves on average five biochemical tests; thyroid as well as orbital imaging is done in 84% of cases. Antithyroid drugs remain the treatment of choice for 94% of respondents, and even so in case of recurrences (66%). For GO, 70% recommend a wait-and-see policy; intervention, preferably with steroids, is advocated by two-thirds of respondents in cases of worsening or still-active eye disease despite euthyroidism.

Adult height in sixty girls with Turner syndrome treated with growth hormone matched with an untreated group.

The main clinical feature of Turner syndrome (TS) is growth failure, with a mean spontaneous adult height ranging between 136 and 147 cm, according to the specific curves of various populations. Though a classical deficiency of GH has not been generally demonstrated, GH has been administered since 1980 in trials, using replacement doses just initially, with a subsequent trend to increase it. We report the outcome of GH therapy given at the fixed dose of 0.33 mg/kg/week in 60 TS girls observed until adult height; 59 untreated TS girls, matched for auxological, karyotypical characteristics and time of observation, born within the same decade served as controls to evaluate GH efficacy. The calculation of the gain in cm over PAH was performed on specific Italian Turner curves, as well as height evaluation as SD score and growth velocity. The same calculations were made using Lyon references and Tanner standards. The mean CA at the beginning of GH treatment was 10.9 +/- 2.76 yr (range 4.5-15.9). Mean adult height of treated group was 151 +/- 6.1 cm with a gain over the PAH calculated at start of therapy (142.9 +/- 5.3 cm) of 8.2 +/- 3.9 cm. Ns change was observed between the PAH at first observation (143.6 +/- 7.0 cm) and adult height (144.3 +/- 5.6 cm) in the control group. Treatment was well tolerated, no relevant side effects were observed, glucose metabolism resulted no more affected than in untreated subjects, IGF-I levels remained within 2 SD. Our results in 60 TS girls, though the dose remained unchanged throughout the treatment, show a good response, characterized by a striking variability in each patient (mean gain in cm over PAH at adult height of 8.17 +/- 3.9, range 3-21 cm), and significant also in comparison with the control group. As the chronological age at start of therapy ranged between 4.5 to 15.9 yr, the results were further evaluated dividing the patients into two groups, according to the age, < or >11 yr. Thirty girls were <11 yr (mean 8.7 +/- 1.76 yr) and 30 were >11 yr (mean 13.2 +/- 1.4 yr). The gain in cm over the PAH in each group was, respectively, 8.1 +/- 3.4 and 8.2 +/- 4.3 cm without any significant difference between the two groups, showing no negative correlation between the CA at the beginning of GH and the response to treatment.

Nasopharyngeal teratoma and diaphragmatic hernia: a non random association?

We describe a female affected by diaphragmatic hernia and nasopharyngeal teratoma. The case is compared with one already reported and possible diagnoses discussed. These cases appear to represent a new syndrome.

Characterization of early presentation idiopathic ovarian failure in girls and adolescents.

This study focused retrospectively on a selected cohort of 20 adolescents with early onset premature ovarian failure (POF) and no apparent underlying cause, in order to characterize the idiopathic ovarian failure at pediatric age. This characterization was based on medical history, pedigree analysis, phenotypical and audiological evaluation, final and target heights, pelvic ultrasonography, endocrine assessment, routine hematochemical analyses and complete autoimmune screening. We found that: a) idiopathic POF presented either before or after puberty onset and also with secondary amenorrhea; b) final height prognosis was impaired only in patients with prepubertal presentation of POF; c) ovarian pattern at ultrasonography and endocrine picture were similar those previously reported in patients with adult onset POF; d) clinical history and pedigree analysis, phenotypical and audiological examination and complete autoimmune screening failed to highlight the existence of any possible cause for POF in 15/20 patients; e) no alterations of total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol serum levels were detected in any patient. On the basis of these results we concluded that: a) final height of the adolescents with POF may be impaired only in patients in whom POF presents as a pubertal delay; b) other parameters do not generally differ from those described by previous reports on young adults with POF, except for serum lipid levels which were normal in the present cohort.

CD45 exon 4 point mutation does not confer susceptibility to type 1 diabetes mellitus or Graves' disease.

A point mutation in the leukocyte common antigen (CD45, C-->G77, exon 4) was investigated in patients with type 1 diabetes (IDDM), patients with Graves' disease and controls. The distribution did not differ significantly between patients and controls. This CD45 variant does not therefore confer susceptibility to either IDDM or Graves' disease.