The use of ultrasensitive thyroglobulin assays reduces but does not abolish the need for TSH stimulation in patients with differentiated thyroid carcinoma.

Measurement of serum Tg using ultrasensitive assays is proposed to replace TSH-stimulated Tg measurement in the follow-up of differentiated thyroid cancer (DTC). Aim of our study was to verify this possibility using two ultrasensitive Tg assays. We selected 215 DTC patients with undetectable (<1 ng/ml) basal serum Tg at the time of a recombinant human TSH (rhTSH) stimulation. According to standard criteria, 173 (80.4%) patients were considered free of disease, 17 (7.9%) had documented disease and 25 (11.7%) had no evidence of disease but detectable serum rhTSH-stimulated Tg (biochemical disease). The sera of these patients were re-assayed with two commercial ultrasensitive assays and the results were compared with the clinical data. Basal Access and E-Iason Tg assays were able to distinguish patients with persistent disease or free of disease with a sensitivity of 82.3 and 82.3%, specificity of 85.5 and 86.1%, positive predictive value (PPV) of 35.8 and 36.8%, negative predictive value (NPV) of 98 and 98.6%, respectively. With both assays the addition of neck ultrasound to basal Tg increased the sensitivity and the NPV to 100% and decreased the false negative rate to 0%. In patients with detectable basal Tg without evidence of disease, serum Tg converted from detectable to undetectable in about 80% of the cases during 2-yr follow-up. Our study indicates that the combination of neck ultrasound and basal ultrasensitive Tg allows to identify all patients free of disease and can decrease the need for rhTSH stimulation in nearly 80% of the patients.

Serum ghrelin levels in growth hormone-sufficient and growth hormone-deficient patients during growth hormone-releasing hormone plus arginine test.

BACKGROUND AND AIMS: Ghrelin is an orexigenic hormone produced in the stomach and in other organs, exerting a wide range of metabolic functions, including stimulation of GH secretion. Ghrelin secretion is decreased by iv or oral glucose load as well as during euglycemic-hyperinsulinemic clamp and hypoglycemia. We evaluated the circulating ghrelin levels in GH-deficient (GHD) and in GH-sufficient (GHS) patients during GHRH plus arginine test. MATERIALS AND METHODS: The study group comprised 35 patients, including 20 with pituitary tumors, 12 with empty sella, 2 with short stature, and 1 with post-traumatic isolated GH deficiency. According to the results of GHRH plus arginine test, 14 patients were defined as GHD and 21 as GHS. Patients with central hypothyroidism, hypocorticism, and hypogonadism had been on replacement therapy for at least 3 months at the moment of the study. Blood samples were collected every 20 min up to 60 min after GHRH and arginine administration. RESULTS: By definition, GH response to GHRH plus arginine was higher in GHS than GHD group (p<0.0001). Basal serum ghrelin levels were not different in the two groups and did not correlate with body mass index, GH, IGFI and insulin concentrations. After GHRH plus arginine, serum ghrelin decreased significantly in both groups, with percent decreases ranging 13.3-66.6% in GHD patients (p=0.001) and 7.2-42.2% in GHS patients (p=0.004), with no significant difference in the two groups (p=0.12). CONCLUSION: Our results show that ghrelin secretion is not modulated by acute GH increase observed in GHS subjects during GHRH plus arginine infusion. The similar decrease of serum ghrelin after GHRH plus arginine stimulation in both GHS and GHD subjects demonstrated that there is no negative feedback of GH on ghrelin secretion.

Early activation of the hypothalamic-pituitary-adrenal-axis in very-low-birth-weight infants with small thymus at birth.

BACKGROUND: An acute thymic involution in human fetuses and newborns has been described in very-low-birth-weight (VLBW) infants with histological chorioamnionitis. However, the mechanisms of thymic involution remain to be clarified. Here, we tested the hypothesis that an activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in VLBW infants with acute thymic involution at birth. METHODS: A total of 180 randomly selected VLBW newborns (28.8 +/- 3.15 wk gestation; 1093 +/- 305 g) entered the study. Thymic size was measured on standard chest radiographs at birth, and expressed as the ratio between the transverse diameter of the cardiothymic image at the level of the carina (CT) and that of the thorax (T). CT/T < 0.28 was considered to indicate a small thymic size. Plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations were determined on days 1 (d-1) and 7 (d-7), and at 1 month (mo-1). Results. A total of 66 (36.7%) newborns had CT/T < 0.28. Infants with small thymus had significantly increased cortisol on d-1 ( approximately 5.2-folds) [median: 18.95 (95% CI: 11.20-39.4) microg/dl vs. 3.66 (1.94-6.82) microg/dl, p < 0.0001)] and d-7( approximately 1.7-folds) [12.0 (4.39-22.97) microg/dl vs. 7.8 (3.63-12.8) microg/dl, p = 0.0384)], as compared with those with normal thymic size, together with higher adrenocorticotropic hormone (ACTH) concentrations on d-1 ( approximately 1.9-folds) [28 (15.6-61.07) pg/ml vs. 14.9 (9.0-23.42) pg/ml, p = 0.0005)], while no significant differences for cortisol at mo-1 or ACTH concentrations on d-7 and mo-1 were evidenced (p > 0.50). From a multivariate logistic regression analysis, a small thymus at birth was a significant independent predictor of plasma cortisol concentrations in the top-quartile (OR = 14.4; 95% CI: 6.079-34.11), and plasma ACTH concentrations in the top-quartile (OR = 4.40 (95% CI: 1.99-9.74) on d-1 (results adjusted for variables significant at univariate analysis). CONCLUSIONS: Our data indicated the presence of a previously unrecognized, early activation of the HPA axis in VLBW newborns with a small thymus at birth.

[The significance of screening tests for aneuploidies in populations at low and high maternal-age-related risk]. / Il significato dei test di screening per le aneuploidie in popolazione a basso e alto rischio per età.

AIM: The aim of this study was to evaluate the validity of the triple test and the screen test in maternal populations at low and high maternal-age-related risk for fetal aneuploidy. METHODS: As a whole, 9,680 pregnant women at low risk and 627 at high risk underwent the triple test; 2,780 pregnant women at low risk and 408 at high risk underwent the screen or combined test; sensitivity, specificity, false positives and detection rate were compared between populations using Student's t-test. RESULTS: The triple test showed a detection rate of 75% in the low and 83.3% in the high risk population with a difference (P<0.003) for detection of trisomies 21 and 18 between the 2 populations; the screen test had a detection rates of 100% and 90% in the 2 populations, respectively, with a difference (P<0.005) between the 2 tests. CONCLUSIONS: Both tests are reliable for screening aneuploidies in the low risk population, the screen test having better performance; in the high risk population, the number of invasive procedures can be reduced by 78% with the triple test and by 84% with the screen test.

Combined analysis of CSF betaA42 peptide and tau protein and serum antibodies to glycosaminoglycans in Alzheimer's disease: preliminary data.

Neuropathological hallmarks of Alzheimer's disease (AD) are amyloid plaques and neurofibrillary tangles, containing betaA(42) peptide and tau protein, respectively. Amyloid plaques contain also glycosaminoglycans (GAGs). Whereas cerebrospinal fluid (CSF) levels of betaA(42) peptide and tau protein have been demonstrated as potential markers of Alzheimer's disease (AD), no data are available for GAGs. We determined (Elisa) tau and betaA(42) CSF levels, as well as serum antibodies to GAGs in 9 AD patients, and the values were analyzed in relation to age and severity of the disease. Beta-A42 and tau CSF levels were significantly reduced and increased, respectively, in AD patients when compared to controls, but they did not correlate with the severity of the disease. Despite their role in amyloidogenesis, we did not find evidence for the use of GAGs as diagnostic marker of AD.

Influence of laboratory homogenization procedures on trace element content of food samples: an ICP-MS study on soft and durum wheat.

Sample contamination as a consequence of abrasion of grinding tools during the homogenization of food materials to be analysed for trace elements was addressed. The possible release of 15 trace elements (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, Sn, V, Zn) from six different grinding and milling devices, operating either continuously or discontinuously, was evaluated. All the devices were commercially available and were representative of models usually employed in food and agricultural laboratories. Wheat grains belonging to one soft and one durum cultivar were used as test material. The determination of the analyte concentrations in subsamples submitted to the different preparation treatments was performed by quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS). Accordingly, a suitable digestion method was developed and the ArC+ interference affecting Cr determination was evaluated and corrected. Statistical differences with respect to the control were detected for 10 elements (Al, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb) and in most cases contamination of the samples was traced back to the composition of the grinding equipment. None of the investigated devices was contamination-free with respect to all of the quantified elements. Abrasion of the grinding tools was higher with durum wheat than with soft wheat as a consequence of their different hardiness.

Hormonal and clinical effects of GnRH agonist alone, or in combination with a combined oral contraceptive or flutamide in women with severe hirsutism.

The objective of this prospective randomized study was to evaluate and compare the hormonal and clinical effects of long-acting gonadotropin-releasing hormone (GnRH) agonist and a combination of GnRH agonist with combined oral contraceptive (COC) or flutamide in women with polycystic ovary syndrome (PCOS). Thirty-five hirsute women with PCOS, ranging in age from 19-27 years, were randomly divided into three groups: group A treated with GnRH agonist (n = 12), group B (n = 12) treated with GnRH agonist plus COC and group C (n = 11) treated with GnRH agonist plus flutamide for 6 months. Before, at the end and 6 months after the end of treatment, blood samples were drawn from all women (in early follicular phase in those with menstrual cycles) to measure ovarian and adrenal androgens, gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), estradiol and estrone plasma levels. The results showed that all three protocols had good therapeutic efficacy. A significant reduction in hirsutism was observed in all patients after 6 months of therapy, the Ferriman-Gallwey scores dropping to 9 +/- 3 in group A, 10 +/- 4 in group B and 11 +/- 5 in group C. Six months after the end of therapy, the hirsutism score continued to be significantly reduced in all groups. After 6 months of therapy, a reduction in plasma levels of LH, FSH, estrone, estradiol, testosterone, free testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) was observed in all groups although this was more pronounced in group B and group C. These therapies may be the basis of future treatments that quickly reduce hirsutism and remove its causes by reducing the secretion of ovarian and adrenal androgens and by blocking androgen receptors.

Thyroid function in early pregnancy. II: Paradoxical growth hormone response to thyrotropin-releasing hormone.

A variant of growth hormone (GH) known as human placental growth hormone (hpGH) is found in maternal serum during pregnancy. It is well established that during the second half of normal pregnancy, pituitary GH secretion is suppressed; however, there are no data about maternal GH secretion during the first trimester of pregnancy. The present study reports the response of GH to thyrotropin-releasing hormone (TRH) in eight pregnant women in the trimester of pregnancy (weeks 6-9) who had previously requested voluntary interruption of pregnancy. The TRH test induced a significant paradoxical GH response with a peak of 9.4 +/- 0.5 ng/ml (mean +/- SD) at 30 min and a higher thyroid-stimulating hormone (TSH) response in pregnant women. The increment was observed until 120 min and no response was observed in the control group. These data show the paradoxical response of GH to TRH, a releasing factor to which the hormone does not normally respond. This paradoxical secretion may be due to direct pituitary stimulation and can be explained on the basis of a state of gestational hypothyroidism.

Solitary plasmacytoma: a case report.

We report a case of solitary vertebral plasmacytoma that was peculiar in mode of onset and neurological course. The clinical and radiological evidence pointed to a generic diagnosis of epidural osteolytic process while electroimmunophoresis of blood narrowed the diagnosis to spinal plasmacytoma, confirmed at operation.

Evaluation of tumor-associated trypsin inhibitor (TATI) in women with benign and malignant gynecological disease.

Tumor-associated trypsin inhibitor (TATI) was assayed in healthy subjects and in women with benign and malignant gynecological diseases. Significantly lower levels were found in boys than in healthy adult subjects. No variations in level were evident over the course of a 24 h period. At a cut-off level of 20 micrograms/l elevated concentrations were found in 42%, 11.4% and 19% of women with ovarian, endometrial and cervical neoplasia, respectively. In patients with ovarian tumors TATI level were elevated both in mucinous and serous tumors. TATI does not seem to be useful for diagnosis of uterine tumors, but could have a specific place in the study and management of ovarian tumors, in which serum concentrations can reach levels 100-200 micrograms/l. In the other gynecological diseases maximum levels of 30-40 micrograms/l were observed.

[Epidemiologic study of epilepsy in the population of Este-Montagnana (U.L.S.S. 22-Veneto Region)]. / Studio epidemiologico dell'epilessia nella popolazione di Este-Montagnana (U.L.S.S. 22 Regione Veneto).

Epidemiological data of the U.L.S.S. n. 22 of Este-Montagnana (PD) show a prevalence of Epilepsy of 5.94%. These data are referred to an observation period of ten years (1978-1987) and confirm the results of major epidemiological trials in U.K. and U.S.A. Distribution by sex and types of crises is the same. The Authors underline the importance of alcohol-related crises; however this is not yet confirmed by precise parallel data.

CA 125 and CA 19-9 in peritoneal, cyst and amniotic fluids.

The concentrations of the tumour markers CA 125 and CA 19-9 were determined in peritoneal, cyst and amniotic fluids, with particular attention being paid to certain reliability criteria of the assay methods. The antigens were measured in undiluted samples and after several dilutions. A recovery test was also performed and protein content evaluated. The results show high levels of CA 125 in all fluids; in descending order of concentration: amniotic (2376-3891 U ml-1), peritoneal (379-4040 U ml-1) and cyst fluid (124-466 U ml-1). Amniotic, peritoneal and cyst fluid concentrations of CA 19-9 were found to be 314-1008 U ml-1, 26.7-2182 U ml-1 and 226-2988 U ml-1, respectively. Recovery was between 80 and 100% for all fluids. CA 125 was easily assayable in all fluids, except amniotic and peritoneal which required dilution even of the samples which fell within the range of the standard curve before dilution. The presence of CA 125 and CA 19-9 in amniotic and cyst fluids emphasizes the non-specificity of these molecules and suggests caution in the interpretation of the results.

Estrogen receptor content in breast cancer: correlation between biochemical and immunohistochemical methods.

Estrogen receptor content of 26 consecutive cases of ductal breast carcinoma was evaluated by using both biochemical and immunohistochemical methods. Agreement was present in 20/26 cases (76.9%). The analysis of discordant cases shows that in 5 cases disagreement is due to sampling error or to prolonged storage before biochemical evaluation. Such cases may reasonably be excluded when correlating results. Linear regression of the remaining 21 cases shows a significant relationship (r = 0.931; p less than 0.001) between biochemical and immunohistochemical values. Results show that immunohistochemical and biochemical assays are largely comparable, and stress the important role of the pathologist in tumor sampling.

[Effects of phosphatidylserine in an experimental model of generalized epilepsy]. / Effetti della fosfatidilserina in un modello sperimentale di epilessia generalizzata.

The possible antiepileptic activity of PS has been tested in a model of generalized epilepsy induced by penicillin in the cat. In acute experiments, topical application to the cortex of PS (from 20 mg/ml to 50 mg/ml) produced a reverse in the polarity of the spike and wave complex and, sometimes, a decrease in the voltage as well as a morphological deformation of s-w bursts. Chronic intraperitoneal administration of PS induced a decrease of the epileptic burst frequency. The effect was already apparent after 14 days and of greater extent after 21 days. Finally the antiepileptic effect of 0,2-0,5 mg/Kg diazepam, given in a single dose during the maximal epileptic activity resulted markedly reinforced in animals chronically treated with PS.