Goiter prevalence and urinary iodine status in urban and rural/mountain areas of Piedmont region.

Piedmont region was reported in the 70s as a mild iodine-deficient area with a goiter prevalence > 10%. This study aimed at characterizing the current status of iodine deficiency in Piedmont, with special attention to putative differences between urban and rural/mountain areas. A cross-sectional, observational study was performed according to the surveillance methods for iodine deficiency disorders recommended by the World Health Organization (WHO). Ultrasound local thyroid volume reference values and median urinary iodine concentration were obtained in 2178 schoolchildren aged 11-15 yr, resident in Piedmont region for more than 5 yr to assess both goiter prevalence and iodine intake. Anamnestic and anthropometric data, thyroid volume by both bimanual palpation and ultrasound were assessed, and spot urinary iodine samples were collected. The median urinary iodine concentration was 115.8 microg/l and the prevalence of goiter 3.1%, indicating this area as iodine-sufficient. Nevertheless, 39% of the schoolchild population had urinary iodine levels < 100 microg/l and 6.8% < 50 microg/l. No differences in goiter prevalence and median urinary iodine excretion were observed between urban and rural/ mountain populations. In conclusion, Piedmont is now an iodine-sufficient region. As no programs of salt iodization have been carried out in the last 30 yr, a silent iodine replacement has occurred. Despite a sufficient median urinary iodine excretion, a program of iodine prophylaxis is strongly recommended due to a large part of iodine-deficient population.

Platelet cGMP inversely correlates with age in healthy subjects.

Biochemical modifications associated with the increase in platelet activity with age are not well defined. Furthermore it is well known that the nitric oxide/cyclic 3', 5'-guanosine monophosphate (cGMP) pathway regulates platelet aggregation. The aim of the present study was to examine the relationship between platelet content of cGMP and age. 120 normal subjects, evaluating the cGMP platelet concentration, 17betaE2, IGF-I, dehydroepiandrosterone sulphate (DHEAS), insulin, plasma glucose, lipid pattern, homocysteine and PAI-I antigen, were studied. The multivariate analysis in a model with cGMP as dependent variable and with age, LDL, apolipoprotein B (ApoB), DHEAS, E2 and insulin-like growth factor (IGF)-I as independent variables shows a negative correlation between cGMP and age (p<0.01, beta=-0.388). In conclusion our data suggest that the reduced efficiency of the system constitutive nitric oxide synthase (cNOS)/guanylate cyclase represents at least one of the reasons of the increased platelet aggregability with age.

Thyroid volume and urinary iodine excretion in the schoolchild population of a Northwestern Italian sub-Alp metropolitan area.

Iodine deficiency is recognised as a major preventable public-health worldwide problem. The aim of this study is to assess local reference values for thyroid volume, and give a snapshot of the epidemiology of goiter and iodine nutritional status of the Turin schoolchild population. Sonographic thyroid volume and median urinary iodine excretion were obtained in 1067 schoolchildren aged 11-15 yr resident in Turin for more than 5 yr to assess both goiter prevalence and iodine intake. All the subjects were asked to fill in a questionnaire about their life habits. Anamnestic and anthropometric data, thyroid volume by both bimanual palpation and ultrasonography were assessed, and spot urinary iodine samples were collected. The results show that the median urinary iodine concentration is 113.1 microg/l and the prevalence of goiter <5%, indicating this area as iodine-sufficient. Nevertheless, 40.5% of the schoolchild population has urinary iodine levels lower than the cut-off level recommended as iodine-sufficiency. Interestingly, the high relative prevalence of ultrasound features of autoimmune thyroid disease suggests autoimmune-thyroiditis as a frequent thyroid disease in Turin schoolchildren. As no active programs of salt, milk or water iodisation have ever been carried out, a silent iodine prophylaxis has probably occurred in the city. Despite a sufficient median urinary iodine excretion, a focused program of iodine prophylaxis should be developed due to the presence of a large rate of iodine-deficient population.

Platelet cyclic guanosine monophosphate production during menstrual cycle in healthy women.

UNLABELLED: The incidence of cardiovascular disease among women during their reproductive years is considerably less than in men and this difference decreases after menopause. Since in cultured endothelial cells and in platelets E2 increases nitric oxide (NO) production, it is possible that their cardioprotective effect may be mediated by NO. The aim of this study was to evaluate platelet cyclic guanosine monophosphate (cGMP), as a marker of NO production, during menstrual cycle. Fifteen women aged 26-40 yr were studied to evaluate: LH, FSH, E2, P and cGMP on the 5th follicular and 22nd luteal day of the cycle and during the ovulatory period. Platelet cGMP was evaluated in basal condition (3-isobuthyl 1-methylxanthine-IBMX) and with ionomycine (IONO) and sodium nitroprusside (SNP). RESULTS: LH, FSH, E2 and P demonstrated the typical patterns of ovulatory cycle. During follicular and luteal IBMX, SNP and IONO phase were homogeneous while they increased during the ovulatory period. A correlation between IBMX cGMP and E2 (p<0.002, rs=0.456) was found. In conclusion the data show an increase in platelet cGMP during the ovulatory period and a correlation between E2 and cGMP suggesting that E2 modulates NO production. The cardioprotective effect of E2 may be, at least in part, mediated by the increase in NO production.

Administration of glutathione in patients with type 2 diabetes mellitus increases the platelet constitutive nitric oxide synthase activity and reduces PAI-1.

Several studies suggest that nitric oxide (NO) production is impaired in diabetes mellitus. Reduced levels of NO could contribute to cardiovascular mortality. Furthermore, NO synthesis is impaired in glutathione (GSH)-depleted human umbilical vein endothelial cells and GSH is reduced in patients with type 2 diabetes mellitus (T2DM). We tested the hypothesis that treatment with GSH may improve platelet constitutive NO sinthase (cNOS) activity in patients with T2DM. Fifteen patients with T2DM underwent a treatment with GSH 600 mg/day i.m. for 10 days. With respect to the basal values on the 10th day of treatment, the red blood cell GSH concentration and platelets cNOS increased (1.4+/-0.1 vs 1.9+/-0.1 micromol/10(10) RBC, p<0.001 and 0.7+/-0.1 vs 2.9+/-0.2 fmol x min(-1) x 10(-9) PLTs, p<0.001, respectively) and the plasma PAI-1 levels diminished (81.4+/-3.7 vs 68.7+/-4.0 ng/ml, p<0.002). A negative correlation between the cNOS and the PAI-1 was found on the basal values. After a wash-out of 30 days the values of red blood cell GSH concentration, platelet cNOS activity and PAI-1 Ag returned to the basal levels. These data suggest that the administration of GSH, in patients with T2DM, is able to improve platelet cNOS activity together with a reduction of PAI-1.

Short procedure of GHRH plus arginine test in clinical practice.

Either in children or in adults, arginine (ARG) alone and combined with GHRH (GHRH+ARG) are reliable tests for the diagnosis of GH deficiency. The procedures of these tests generally include GH measurement every 15 min from baseline up to 90-120 min. Aim of our study was to verify if the procedure of these tests could be usefully shortened in clinical practice. To this goal we have studied 173 normally growing children and adolescents (C, 117 M and 56 F, age: 11.3 +/- 0.4 yr.) and 125 young and middle aged normal adults (A, 68 M and 57 F, age: 30.0 +/- 0.6 yr.). ARG alone test was performed by 81 C and 33 A (0.5 g/kg arginine, i.v., from 0 to +30 min, up to a maximum of 30 g) while GHRH (1 microg/kg i.v. bolus at 0 min) + ARG test was performed by 92 C and 92 A. After ARG alone, taking into account data from +15 to +105 min, GH values above the 3rd centile limit of arbitrary cut-off (7 or 10 microg/l in C and 5 microg/l in A) occurred in 85% or 64% and 94% subjects, respectively. After GHRH+ARG test, taking into account only data at +30, +45, +60 min GH values above the 3rd centile limit (20 microg/l in C and 16.5 microg/l in A) occurred in 99% of subjects in both groups. Taking into account only these 3 timing points, the percentage of GH peak above the third centile limits after ARG alone was never higher than 60% in C and 85% in A. In conclusion, this study shows that single GHRH+arginine test can be reliably performed in a shortened procedure which makes easier the clinical practice and further reduces costs.

Serum DHEAS levels correlate with platelet cGMP in normal women.

Several studies suggest that DHEAS is a protective factor against atherosclerosis and coronary artery disease in man, but the mechanism of its biological role is unclear. Recently, it has been suggested that DHEAS can retard atherosclerosis formation through an increase in nitric oxide (NO) production by increasing E2 synthesis. The aim of the study was to evaluate the platelet cGMP concentrations (i.e. a marker of NO production) and the serum levels of DHEAS and E2 in normal females. Blood samples were taken from 51 normal women (age 42.3+/-1.9 yr, range: 22-67 yr, BMI 23.0+/-0.6 kg/m2) to evaluate platelet cGMP concentrations and serum levels of DHEAS and E2. To determine the platelet cGMP content, platelet rich plasma (PRP) was incubated at 37 C (30 min) in the presence of IBMX. The amount of platelet cGMP was measured by a cGMP (3H) assay kit. In all subjects the mean of platelet cGMP was 536.2+/-45.3 fmol/10(6) platelets and the mean of serum DHEAS and E2 was 151.4+/-13.9 microg/dl and 34.7+/-6.1 pg/ml, respectively. In all subjects DHEAS positively correlates with cGMP (p<0.001, r=0.513) and with E2 (p<0.001, r=0.650); furthermore E2 positively correlates with cGMP (p<0.001, r=0.663). In conclusion our data support the hypothesis that DHEAS exerts its antiatherogenic effect by increasing the NO production directly and/or by increasing the E2 synthesis.

The negative GH auto-feedback in childhood: effects of rhGH and/or GHRH on the somatotroph response to GHRH or hexarelin, a peptidyl GH secretagogue, in children.

Aim of the present study was to further clarify the negative GH auto-feedback mechanisms in childhood. To this goal we studied the effects of rhGH and/or GHRH administration on the GH response to GHRH or hexarelin (HEX), a peptidyl GH secretagogue, in normal short children. In 34 prepubertal children (12 girls and 22 boys, age 8.2- 14.2 yr) with normal short stature (normal height velocity and IGF-I levels) the following tests were performed: group A (no.=11): GHRH (GHRH 1 - 29, Geref, Serono; 1 microg/kg iv at 150 min) preceded by saline or GHRH at 0 min; group B (no.=6): GHRH preceded by saline or rhGH (0.005 IU/kg iv at 0 min); group C (no.=6): GHRH preceded by rhGH alone or combined with GHRH; group D (no.=6): HEX (2 microg/kg iv at 150 min) alone or preceded by rhGH. In group A, the GH response to GHRH was not modified by pre-treatment with GHRH (GH peak, mean+/-SEM: 16.7+/-2.9 vs 15.1+/-2.3 microg/l, respectively). In group B, the GH response to GHRH was clearly inhibited by rhGH (8.7+/-2.3 vs 38.8+/-4.5 microg/l, p<0.001); the GH rise after rhGH in group B overlapped with that after GHRH in group A. In group C, the GH response to GHRH after pre-treatment with rhGH (13.2+/-4.0 microg/l) was similar to that in group B and was not significantly modified by pre-treatment with rhGH+ GHRH (6.9+/-2.7 microg/l); the GH rise after rhGH+GHRH was higher (p<0.05) than that after rhGH alone. In group D, the GH response to HEX was significantly blunted by pre-treatment with rhGH (34.1+/-11.7 vs 51.2+/-17.9 microg/l, p<0.05). Our results demonstrate that in childhood the somatotroph response to GHRH is preserved after GHRH while it is inhibited after rhGH administration, which is also able to blunt the GH response to HEX. Thus, the somatostatin-mediated negative GH auto-feedback is already operative in childhood; the reason why the GHRH- induced GH rise is not inhibited by GHRH pre-treatment is unexplained.

Sequential administration of arginine and arginine plus GHRH to test somatotroph function in short children.

The hormonal diagnosis of GH deficiency in childhood is conventionally based on the GH response to at least two provocative stimuli. Among these, arginine (ARG) has long been considered a classical, centrally mediated stimulus of GH secretion. ARG is also able to potentiate the GH response to GHRH, likely inhibiting hypothalamic somatostatin; this combined test is one of the most potent to explore the maximal secretory capacity of somatotroph cells. Based on these premises, we verified whether the sequential administration of ARG and ARG+GHRH could be feasible as single step provocative test to evaluate the GH releasable pool in short children. To this goal, 48 normal short children (35 M and 13 F, 12.0+/-0.4 yr, PS 1: 255 II-IV: 23) underwent a test with ARG (0.5 g/kg i.v. from 0 to +30 min) followed by a coadministration of ARG (from +120 to 150 min) plus GHRH (1 microg/kg i.v. at +120 min). ARG alone elicited a clear GH response (mean peak vs baseline: 12.1+/-1.7 vs 2.0+/-0.4 microg/l, p<0.001, Cmax range 12-51.0 microg/l). Following this GH rise, the hormonal levels at +120 min approached to baseline levels (4.2+/-0.8 microg/l) but then showed marked response to the coadministration of ARG+GHRH. The GH peak following ARG+GHRH (mean peak: 47.8+/-3.3 microg/l, p<0.001; Cmax 22.4-150.0 microg/l) was clearly higher (p<0.001) than that recorded after ARG alone. The GH responses to both ARG and ARG+GHRH were independent of gender, puberty, height velocity, body mass index (BMI) and IGF-I levels. Nine normal short children (16%) had GH peaks lower than 7 microg/l after ARG alone, while none showed GH peak below 20 microg/l after ARG+GHRH. Thus, ARG alone is a good stimulus of GH secretion but false positive responses frequently occur in normal short children. ARG+GHRH is a more potent stimulus giving no false positive responses even after previous challenge with ARG alone. Testing with sequential administration of ARG and ARG+GHRH may allow the single step evaluation of the somatotroph response to central and pituitary stimuli in short children.

Reduction of the pituitary GH releasable pool in short children with GH neurosecretory dysfunction.

OBJECTIVES: The classical 'GH neurosecretory dysfunction' (GHNSD) refers to slowly growing children with normal GH responses to classical provocative tests but impaired spontaneous GH secretion over 24 h frequently leading to low IGF-I levels. Thus it has been assumed that these subjects have insufficiency of spontaneous GH secretion due to neuroendocrine abnormalities in spite of a normal releasable pool of GH. However, classical provocative tests do not reliably assess the maximal somatotroph capacity; thus it is still unclear if the GH pool is really preserved or not. GHRH + arginine test is more potent than the classical tests and evaluates the maximal secretory capacity of somatotroph cells. The GH response to this stimulus is reproducible and also independent of age and puberty. DESIGN AND PATIENTS: We studied the GH response to GHRH (1 microgram/kg iv) + arginine (ARG, 0.5 g/kg iv) in 19 short children with GHNSD (14 boys and 5 girls, age: 12.1 +/- 0.7 years, pubertal stages I-III, HV-SDS between -1.6 and -4.9; GH peak > 10 micrograms/l after classical stimuli but mean GH concentration (mGHc) < 3 micrograms/l). The results in GHNSD were compared with those in 38 short children with idiopathic or organic severe GHD (GHD, 29 boys and 9 girls, age: 11.2 +/- 0.6 years, pubertal stages I-III, HV-SDS between -1.8 and -4.4; GH peak < 10 micrograms/l after 2 classical provocative tests) and in 83 children with normal or familial short stature (NC, 59 boys and 24 girls, age: 11.5 +/- 0.3 years., pubertal stages I-III; HV-SDS > 25th centile, normal IGF-I levels). RESULTS: Mean IGF-I levels in GHNSD (121.9 +/- 20.3 micrograms/l) were lower (P < 0.001) than those in NC (270.3 +/- 13.8 micrograms/l) but higher (P < 0.001) than those in GHD (72.0 +/- 4.0 micrograms/l). The mean GH concentration (mGHc) in GHNSD (2.1 +/- 0.1 micrograms/l) was lower (P < 0.01) than that in NC (4.9 +/- 0.5 micrograms/l) but higher (P < 0.01) than that in GHD (1.5 +/- 0.2 micrograms/l). On the other hand, the mean peak GH response to GHRH + ARG in GHNSD (43.7 +/- 3.7 micrograms/l) was markedly higher (P < 0.001) than that in GHD (8.2 +/- 0.9 micrograms/l) but significantly lower (P < 0.01) than that in NC (60. 4 +/- 2.7 micrograms/l). All GHD patients had peak GH responses to GHRH + ARG below the 3rd centile limit of normality (20 micrograms/l), while all GHNSD patients had peak GH responses within the normal range. No significant correlation was found between GH peak after GHRH + ARG, mGHc and IGF-I levels in each group. CONCLUSION: Our study demonstrates that short children with 'GH neurosecretory dysfunction' show reduction in the GH releasable pool evaluated by the provocative and potent GHRH + arginine test. However, the peak GH response to a single GHRH + arginine test in GH neurosecretory dysfunction is always within the normal range indicating that this test as well as classical stimuli does not distinguish normal subjects from GH neurosecretory dysfunction.

[Prognostic factors in the treatment of carcinoma of the cervix uteri in IB-IIA stage. Retrospective study]. / Fattori prognostici nel trattamento del carcinoma del collo dell'utero negli stadi IB-IIA. Studio retrospettivo.

January, 1977, to December, 1990, 311 patients with stage IB-IIA cervix carcinoma were treated at the Radiotherapy Department of the University of Turin. The distribution by stage was: 232 T1b (74.6%) and 79 T2a (25.4%). One hundred and eighty-nine patients (77% T1b-23% T2a) underwent preoperative radiotherapy, 63 patients (58% T1b-42% T2a) radiotherapy alone and 59 (85% T1b-15% T2a) postoperative radiotherapy. The first group of patients was treated according to three treatment protocols, based on different surgical procedures. During the median follow-up period of 86 months (82.6% of the patients underwent a minimum 3-year follow-up), 55 locoregional relapses (17%) and 21 extrapelvic metastases (7%) were observed. The 5-year NED survival rate and local control was 80%. The prognostic factors which significantly influenced survival in the univariate analysis, were: disease stage (p < .01), age (p < .05), the period between first symptom and therapy (p = .01), treatment protocols (radiotherapy combined with surgery versus radiation therapy alone: p < .05), residual disease after brachytherapy (p < .01), nodal status (p < .00001). In the radiotherapy alone group, the total dose influence on survival was not statistically significant (p = .12). In our series, histology and surgical procedures did not seem to influence prognosis. In the multivariate analysis, treatment protocol, age and residual disease after brachytherapy did not influence the prognosis, whereas the total dose of radiotherapy, pain (as first symptom) and Wertheim-Meigs surgery approach are prognostic factors. Severe late-effects were 17: 13 in the radiotherapy plus surgery protocol and 4 in the radiotherapy alone protocol. The incidence of major complications seems to correlate with surgical impact.

An unusual case of chronic myelocytic leukemia characterized by a conspicuous tissue infiltration treated with leukapheresis.

An unusual case of chronic myelocytic leukemia (CML) is described that presented leukocytosis at onset (720 X 10(9)/l), symptoms of stasis, organomegaly, and a conspicuous infiltration of leukemic cells from the pelvis to the right popliteal cavity. As initial therapy and in addition to chemotherapy, six therapeutic leukapheresis treatments (TL) were performed and the patient showed dramatic symptomatic improvement with reduction in leukocytosis (97 X 10(9)/l), organomegaly, and tissue infiltration.

[Use of the pancreolauryl test in the diagnosis of exocrine pancreatic insufficiency. Preliminary results]. / Utilizzazione del pancreolauryl test nella diagnosi di insufficienza pancreatica esocrina. Risultati preliminari.

The Pancreolauryl Test (PLT), a tubeless test used to study exocrine pancreatic function, was performed in 18 patients (8 healthy controls and 10 patients with suspected chronic pancreatitis) to evaluate its sensitivity and clinical applicability. The sensitivity rate of PLT was 75%, the specificity 85.7%, the predictive value of a positive test 60% and of a negative test 92.3%. The PLT proved to be a non invasive, easy to perform test; besides it was acceptable to the patients, without collateral effects.

VIP-like and GFAP-like immunoreactivities in the chicken brain stem. II. The pons and the tegmentum of the mesencephalon.

An immunocytochemical analysis was performed on the chicken pons and mesencephalon (except the optic tectum) according to the PAP-DAB procedure, to study the distribution here of the neurons reacting to anti-VIP antibodies and the gliocytes reacting to anti-GFAP antibodies. Positive and negative controls were carried out in both the immunoreactions. The VIP-immunoreactive neurons showed a distribution essentially corresponding to that observed in other species by various Authors. They appeared scattered mainly in 3 sites: (a) the subventricular grey between pons and mesencephalon; (b) the periaqueductal grey, up to the diencephalon; (c) the rostro-ventral portion of the mesencephalic tegmentum, up to the diencephalon. Furthermore, some perivascular VIP-immunoreactive neuronal processes were seen. No differences have so far been detected as regards the GFAP-like immunoreactivity distribution, in comparison with the data reported by the authors in the chicken medulla and by others in in the brain stem of some other species.

[Effects of radiation emission of the CO2-laser on embryonal ocular bulb tissues (Gallus gallus)]. / Effetti delle radiazioni emesse da un laser-CO2 su tessuti del bulbo oculare embrionale (Gallus gallus).

The wall of the eye bulbs of 15 chick embryos, immediately after their transfer to Hanks fluid, was irradiated with a CO2 laser, focused on the 12th conjunctival papilla or on its prospective area. This 'in vitro' irradiation was performed under the following main parameters: (a) beam power congruent to 4W; (b) exposure time = 1/30 sec; (c) thickness of the fluid (Hanks solution) on the target surfaces = 0, 3 divided by 0, 7 mm. The same area of the eye bulb surface of other 15 chick embryos was irradiated 'in ovo' under the following conditions: (a) congruent to 4W; (b) = 1/10 sec; (c) (amniotic fluid + albumen) = 1 divided by 1, 5 mm. In the L/M analysis so far carried out, the lesions produced 'in vitro' and 'in ovo' showed a number of qualitative resemblances: i.e., disappearance of epithelial cells and numerous pyknoses in the cells left 'in situ'; decrease in thickness of the outer layer of the scleral mesenchyme, whose cells appeared closer to each other-owing to reduction of the intercellular spaces-, and often pyknotic. It is possible that the same mechanisms underlie such morphological aspects, observed in both groups of irradiated eyes. On the other hand, some quantitative differences were observed between the 'in vitro' and 'in ovo' lesions, the extent in surface and depth of the latter being appreciably lesser. Presumably the genesis of such differences could have been influenced by the physico-chemical differences between the fluids covering the target surfaces: Hanks fluid and, respectively, amniotic fluid + albumen.(ABSTRACT TRUNCATED AT 250 WORDS)

[Histomorphogenesis of spinal ganglia developing on the chorioallantoic membrane]. / Analisi dell'istomorfogenesi di gangli spinali che si sviluppano sulla membrana corio-allantoidea.

The aim of the present research is to study the development of spinal ganglia implanted onto chorio-allantoic membrane (CAM), where they are supplied by 'foreign', extraembryonic vessels. Small blocks including a segment of the neural tube and 4 pairs of somites were isolated from the brachial or thoracic or lumbar region (neuromeres C13 - T1 or T3 - T6 or L1 - L4) of thirty 3-day donor chick embryos and grafted on the CAM of as many 10-day host chick embryos. At regular time intervals after grafting, the implants were fixed, embedded in paraffin, serially cross-sectioned and stained. The preliminary results are similar for the ganglia from the 3 regions: they seem to indicate that in the spinal ganglia grafted on the CAM the developing blood vessels do not exert any morphogenetic influence on the substratum; this corroborates results from previous researches (2) on the normally 'in situ' developing ganglia. It is now the author purpose to submit to a careful analysis a datum from the present research: namely, the earlier appearance of the endoganglionic vessels in the brachial and lumbar grafted ganglia than in the thoracic ones.