New insights on the active degassing system of the Lipari-Vulcano complex (South Italy) inferred from Local Earthquake Tomography.

Seismic tomography is a very powerful and effective approach to look at depths beneath volcanic systems thus helping to better understand their behaviour. The P-wave and S-wave velocity ratio, in particular, is a key parameter useful to discriminate the presence of gas, fluids and melts. We computed the first 3-D overall model of Vp, Vs and Vp/Vs for the Lipari-Vulcano complex, central sector of the Aeolian volcanic archipelago (southern Italy). The investigated area has been characterized in recent times by fumaroles, hydrothermal activity and active degassing. In particular, in the Vulcano Island, several episodes of anomalous increases of fumarole temperature and strong degassing have been recorded in the past decades and the last "crisis", started in September 2021, is still ongoing. For tomographic inversion we collected ~ 4400 crustal earthquakes that occurred in the last thirty years and we used the LOcal TOmography Software LOTOS. The results clearly depicted two low Vp and Vp/Vs anomalies located up to ~ 8 km depths below Vulcano and the western offshore of Lipari, respectively. These anomalies can be associated to the large presence of gas and they furnish a first picture of the gas-filled volumes feeding the main degassing activity of the area.

Factors associated with enrolment in clinical trials among women with early-stage breast cancer.

BACKGROUND: Clinical trials allow development of innovative treatments and ameliorate the quality of clinical care in oncology. Data show that only a minority of patients are enrolled in clinical trials. We assessed enrolment in clinical trials and its correlates among women with early breast cancer. METHODS: We included 9516 patients with stage I-III breast cancer from the multicenter, prospective CANTO study (NCT01993498), followed-up until year 4 (Y4) post-diagnosis. We assessed factors associated with enrolment using multivariable logistic regression. In exploratory, propensity score matched analyses, we used multiple linear regression to evaluate the relationship of enrolment in clinical trials with the European Organisation for Research and Treatment of Cancer Quality Of Life (QoL) questionnaire (EORTC QLQ-C30) Summary Score and described clinical outcomes (distant disease event, invasive disease event, and death by any cause) according to enrolment. RESULTS: Overall, 1716 patients (18%) were enrolled in a clinical trial until Y4 post-diagnosis of breast cancer. Socioeconomic factors were not associated with enrolment. Centres of intermediate volume were most likely to enrol patients in clinical trials [versus low volume, odds ratio 1.45 (95% confidence interval (CI) 1.08-1.95), P = 0.0124]. Among 2118 propensity score matched patients, enrolment was associated with better QoL at Y4 (adjusted mean difference versus not enrolled 1.37, 95% CI 0.03-2.71, P = 0.0458), and clinical outcomes (enrolled versus not enrolled, distant disease event 7.3% versus 10.1%, P = 0.0206; invasive disease event 8.2% versus 10.5%, P = 0.0732; death by any cause 2.8% versus 3.7%, P = 0.2707). CONCLUSIONS: In this large study, one in five patients enrolled on a clinical trial until Y4 after diagnosis of early breast cancer. Geographical and centre-related factors were significantly associated with enrolment in clinical trials. Inclusion in clinical trials seemed associated with improved QoL and clinical outcomes. Access to innovation for early-stage breast cancer patients should be encouraged and facilitated by overcoming organizational and geographical barriers to recruitment.

Muographic monitoring of the volcano-tectonic evolution of Mount Etna.

At Mount Etna volcano, the focus point of persistent tectonic extension is represented by the Summit Craters. A muographic telescope has been installed at the base of the North-East Crater from August 2017 to October 2019, with the specific aim to find time related variations in the density of volcanic edifice. The results are significant, since the elaborated images show the opening and evolution of different tectonic elements; in 2017, a cavity was detected months before the collapse of the crater floor and in 2018 a set of underground fractures was identified, at the tip of which, in June 2019, a new eruptive vent started its explosive activity, still going on (February, 2020). Although this is the pilot experiment of the project, the results confirm that muography could be a turning point in the comprehension of the plumbing system of the volcano and a fundamental step forward to do mid-term (weeks/months) predictions of eruptions. We are confident that an increment in the number of telescopes could lead to the realization of a monitoring system, which would keep under control the evolution of the internal dynamic of the uppermost section of the feeding system of an active volcano such as Mount Etna.

Polymer-coated fiber optic probe for the monitoring of breathing pattern and respiratory rate.

In recent years, no-invasive and small size systems are meeting the demand of the new healthcare system, in which the vital signs monitoring is gaining in importance. In this context, Fiber Bragg grating (FBG) sensors are becoming very popular and FBG-based systems could be used for monitoring vital signs. At the same time, FBG could be able to sense chemical parameters by the polymer functionalization. The aim of our study was investigating the ability of a polymer-coated FBG-based probe for monitoring breathing patterns and respiratory rates. We tested the proposed FBG-based probe on 9 healthy volunteers during spirometry, the most common pulmonary function test. Results showed the high accuracy of the proposed probe to detect respiratory rate. The comparison between the respiratory rates estimated by the probe with the ones by the spirometer showed the absolute value of the percentage errors lower than 2.07% (in the 78% of cases <.91%). Lastly, a Bland Altman analysis was performed to compare the instantaneous respiratory rate values gathered by the spirometer and the FBG probe showing the feasibility of breath-by-breath monitoring by the proposed probe. Results showed a bias of 0.06± 2.90 $\mathrm{breaths}\square {\mathrm {min}}^{-1}$. Additionally, our system was able to follow the breathing activities and monitoring the breathing patterns.

Wearable textile based on silver plated knitted sensor for respiratory rate monitoring.

Wearable systems are gaining broad acceptance for monitoring physiological parameters in several medical applications. Among a number of approaches, smart textiles have attracted interest because they are comfortable and do not impair patients' movements. In this article, we aim at developing a smart textile for respiratory monitoring based on a piezoresistive sensing element. Firstly, the calibration curve of the system and its hysteresis have been investigated. Then, the proposed system has been assessed on 6 healthy subjects. The volunteers were invited to wear the system to monitor their breathing rate. The results of the calibration show a good mean sensitivity (i.e., approximately 0.11V·%-1); although the hysteresis is not negligible, the system can follow the cycles also at high rates (up to 36 cycle·min-1). The feasibility assessment on 6 volunteers (two trials for each one) shows that the proposed system can estimate with good accuracy the breathing rate. Indeed, the results obtained by the proposed system were compared with the ones collected with a spirometer, used as reference. Considering all the experiments, a mean percentage error was approximately 2%. In conclusion, the proposed system has several valuable features (e.g., the sensing element is lightweight, the sensitivity is high, and it is possible to develop comfortable smart textile); in addition, the promising performances considering both metrological properties and assessment on volunteers foster future tests focused on: i) the possibility of developing and system embedding several sensing elements, and ii) to develop a wireless acquisition system, to allow comfortable and long-term acquisition in both patients and during sport activities.

The NUMEN project: Heavy-Ion Double Charge Exchange reactions towards 0νββ NME determination / El proyecto NUMEN: reacciones de intercambio de cargas dobles de iones pesados hacia la determinación de 0νββ NME

Abstract NUMEN proposes cross sections measurements of Heavy-Ion double charge exchange reactions as an innovative tool to access the nuclear matrix elements, entering the expression of the life time of Neutrinoless double beta decay (0νββ). A key aspect of the projectis the use at INFN-Laboratori Nazionali del Sud (LNS) of the Superconducting Cyclotron (CS) for the acceleration of the required high resolution and low emittance heavy-ion beams and of MAGNEX large acceptance magnetic spectrometer for the detection of the ejectiles. The experimental measurements of double charge exchange reactions induced by heavy ions present a number of challenging aspects, since such reactions are characterized by very low cross sections. First experimental results give encouraging indication on the capability to access quantitative information towards the determination of the Nuclear Matrix Elements for 0νββ decay.

Resumen NUMEN propone mediciones de secciones eficaces de reacciones de intercambio de carga doble de iones pesados como una herramienta innovadora para acceder a los elementos de la matriz nuclear, entrando en la expresión del tiempo de vida de la desintegración beta doble sin neutrino (0νββ). Un aspecto clave del proyecto es el uso en INFN-Laboratori Nazionali del Sud (LNS) del ciclotrón superconductor (CS) para la aceleración de los haces de iones pesados de alta resolución y baja emitancia requeridos y del espectrómetro magnético de gran aceptación MAGNEX para la detección de los residuos eyectados. Las mediciones experimentales de reacciones de intercambio de carga doble inducidas por iones pesados presentan una serie de aspectos desafiantes, ya que tales reacciones se caracterizan por secciones eficaces muy bajas. Los primeros resultados experimentales dan una indicación alentadora sobre la capacidad de acceder a información cuantitativa para la determinación de los Elementos de la Matriz Nuclear para la descomposición de 0νββ.

Maternal hemodynamics early in labor: a possible link with obstetric risk?

OBJECTIVE: To determine if hemodynamic assessment in 'low-risk' pregnant women at term with an appropriate-for-gestational age (AGA) fetus can improve the identification of patients who will suffer maternal or fetal/neonatal complications during labor. METHODS: This was a prospective observational study of 77 women with low-risk term pregnancy and AGA fetus, in the early stages of labor. Hemodynamic indices were obtained using the UltraSonic Cardiac Output Monitor (USCOM® ) system. Patients were followed until the end of labor to identify fetal/neonatal and maternal outcomes, and those which developed complications of labor were compared with those delivering without complications. RESULTS: Eleven (14.3%) patients had a complication during labor: in seven there was fetal distress and in four there were maternal complications (postpartum hemorrhage and/or uterine atony). Patients who developed complications during labor had lower cardiac output (5.6 ± 1.0 vs 6.7 ± 1.3 L/min, P = 0.01) and cardiac index (3.1 ± 0.6 vs 3.5 ± 0.7 L/min/m2 , P = 0.04), and higher total vascular resistance (1195.3 ± 205.3 vs 1017.8 ± 225.6 dynes × s/cm5 , P = 0.017) early in labor, compared with those who did not develop complications. Receiver-operating characteristics curve analysis to determine cut-offs showed cardiac output ≤ 5.8 L/min (sensitivity, 81.8%; specificity, 69.7%), cardiac index ≤ 2.9 L/min/m2 (sensitivity, 63.6%; specificity, 76.9%) and total vascular resistance > 1069 dynes × s/cm5 (sensitivity, 81.8%; specificity, 63.6%) to best predict maternal or fetal/neonatal complications. CONCLUSIONS: The study of maternal cardiovascular adaptation at the end of pregnancy could help to identify low-risk patients who may develop complications during labor. In particular, low cardiac output and high total vascular resistance are apparently associated with higher risk of fetal distress or maternal complications. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Restricted physical activity in pregnancy reduces maternal vascular resistance and improves fetal growth.

OBJECTIVES: To test the efficacy of maternal activity restriction for reducing peripheral vascular resistance in normotensive pregnant women with raised total vascular resistance (TVR) and to evaluate its effect on fetal growth. METHODS: This was a prospective case-control study of 30 women enrolled between 27 and 29 weeks' gestation. All patients met the following criteria: normal blood pressure before and during pregnancy, TVR between 1300 and 1400 dynes × s/cm5 at enrolment, normal fetal Doppler parameters at enrolment and abdominal circumference between the 10th and 25th centiles. Patients were assigned to activity restriction (activity-restriction group; n = 15) or no treatment (control group; n = 15) and were assessed after 4 weeks for TVR and fetal growth. RESULTS: TVR at enrolment and estimated fetal weight centile were similar in the activity-restriction group vs controls (1358 ± 26 vs 1353 ± 30 dynes × s/cm5 ; 18th ± 4 vs 19th ± 4 centile; P = NS). After 4 weeks, the activity-restriction group compared with controls showed significantly lower TVR (1165 ± 159 vs 1314 ± 190 dynes × s/cm5 ; P < 0.05), which was associated with higher estimated fetal weight centile (25th ± 5 vs 20th ± 5 centile; P < 0.05). TVR was lower and estimated fetal weight centile higher for the activity-restriction group after 4 weeks compared with at enrolment. CONCLUSIONS: In normotensive pregnant women with raised TVR, maternal activity restriction appears to be effective in reducing TVR and therefore enhancing fetal growth. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Correlation between maternal body composition and haemodynamic changes in pregnancy: different profiles for different hypertensive disorders.

OBJECTIVES: To assess and correlate changes in body composition and haemodynamic function during pregnancy. To identify different haemodynamic profiles based on the onset of hypertensive diseases such as gestational hypertension and preeclampsia. METHODS: We enrolled 265 healthy, normotensive pregnant women throughout pregnancy (from 6+0 to 36+0weeks). They were subjected to assessment of body composition and haemodynamic function using non-invasive methods. We divided our population in three groups: group A with physiological pregnancy, group B with gestational hypertension and group C with preeclamptic patients. RESULTS: In patients who developed gestational hypertension we found lower total body water (TBW) percentage, higher Fat Mass (FM), associated with lower Cardiac Output (CO) and higher Total Vascular Resistance (TVR) during the second trimester. In the third trimester we didn't find haemodynamic differences, but a significative increase in extracellular water (ECW) percentage. In patients who developed preeclampsia we found since the first trimester significative higher TVR and hypodynamic circulation, associated with lower FM percentage. CONCLUSIONS: Assessment of body composition and maternal cardiac function may help to identify earlier in pregnancy, patients with different (mal) adaptations to pregnancy. Women with high TVR, hypodynamic circulation and low fat mass during the first trimester, might be at higher risk to develop preeclampsia. Patients with higher BMI and FM percentage, and increased TVR in the second trimester, might be at risk of gestational hypertension and excessive fluid retention at the end of pregnancy.

A wearable textile for respiratory monitoring: Feasibility assessment and analysis of sensors position on system response.

The interest on wearable textiles to monitor vital signs is growing in the research field and clinical scenario related to the increasing demands of long-term monitoring. Despite several smart textile-based solutions have been proposed for assessing the respiratory status, only a limited number of devices allow the respiratory monitoring in a harsh environment or in different positions of the human body. In this paper, we investigated the performances of a smart textile for respiratory rate monitoring characterized by 12 fiber optic sensors (i.e., fiber Bragg grating) placed on specific landmarks for compartmental analysis of the chest wall movements during quiet breathing. We focused on the analysis of the influence of sensor position on both peak-to-peak amplitude of sensors output and accuracy of respiratory rate measurements. This analysis was performed on two participants, who wore the textile in two positions (i.e., standing and supine). Bland-Altman analysis on respiratory rate showed promising results (better than 0.3 breaths per minute). Referring to the peak-to-peak output amplitude, the abdomen compartment showed the highest excursions in both the enrolled participants and positions. Our findings open up new approaches to design and develop smart textile for respiratory rate monitoring.

Design and characterisation of a real time proton and carbon ion radiography system based on scintillating optical fibres.

This paper describes the design and characterization of a charged particle imaging system composed of a position sensitive detector and residual range detector. The position detector consists of two identical overlying and orthogonal planes each of which consists of two layers of pre-aligned and juxtaposed scintillating fibres. The 500µm square section fibres are optically coupled to two Silicon Photomultiplier arrays using a channel reduction system patented by the Istituto Nazionale di Fisica Nucleare. The residual range detector consists of sixty parallel layers of the same fibres used in the position detector each of which is optically coupled to a Silicon Photomultiplier array by wavelength shifting fibres. The sensitive area of the two detectors is 9×9cm(2). Characterising the position sensitive and the residual range detectors to reconstruct the radiography, is fundamental to validating the detectors' designs. The proton radiography of a calibrated target in imaging conditions is presented. The spatial resolution of the position sensitive detector is about 150µm and the range resolution is about 170µm. The performance of the prototypes were tested at CATANA proton therapy facility (Laboratori Nazionali del Sud, INFN, Catania) with energy up to 58MeV and rate of about 10(6) particles per second. The comparison between the simulations and measurements confirms the validity of this system.

Preterm delivery and elevated maternal total vascular resistance: signs of suboptimal cardiovascular adaptation to pregnancy?

OBJECTIVE: To evaluate the maternal hemodynamic profile in women with a diagnosis of threatened preterm delivery (TPD) in order to understand the possible pathophysiologic mechanism leading to an increased lifetime risk for future cardiovascular disease. METHODS: Patients with a diagnosis of TPD were enrolled and assessed using a non-invasive method (USCOM® ) for the determination of hemodynamic parameters. Vaginal and rectal swabs were taken, cervical length, blood inflammatory indices, fetal blood-vessel Doppler velocimetry were measured and gestational age at the time of delivery and neonatal outcomes were noted. RESULTS: A total of 68 patients were enrolled and included in the analysis. The population was divided into two groups according to total vascular resistance (TVR): Group A with a TVR of ≤ 1000 dynes × s/cm5 (n = 48) and Group B with a TVR of > 1000 dynes × s/cm5 (n = 20). C-reactive protein (CRP) was higher in Group B than in Group A, suggesting a systemic inflammation status. Group B delivered earlier (32 + 4 weeks vs 38 + 2 weeks; P < 0.01) and neonatal outcome was worse than in Group A. Significantly lower values of cardiac output, stroke volume, peak velocity of flow, velocity time integral, minute distance, stroke volume index, cardiac index, stroke work, cardiac power, inotropy index and potential-to-kinetic energy ratio were observed in Group B than in Group A. CONCLUSIONS: Women with a diagnosis of TPD showing TVR values of > 1000 dynes × s/cm5 and elevated levels of CRP are at high risk of preterm delivery. An impaired maternal cardiovascular adaptation during pregnancy in these patients might suggest a possible higher risk for subsequent future cardiovascular disease. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Reproductive function in male patients with type 1 diabetes mellitus.

This study was undertaken to evaluate conventional and some of the main bio-functional spermatozoa parameters, serum gonadal hormones and didymo-epididymal ultrasound features in patients with type 1 diabetes mellitus (DM1). DM1 affects an increasing number of men of reproductive age. Diabetes may affect male reproduction by acting on the hypothalamic-pituitary-testicular axis, causing sexual dysfunction or disrupting male accessory gland function. However, data on spermatozoa parameters and other aspects of the reproductive function in these patients are scanty. Thirty-two patients with DM1 [27.0 (25.0-30.0 years)] and 20 age-matched fertile healthy men [28.0 (27.25-30.75 years)] were enrolled. Patients with diabetic neuropathy, other endocrine disorders or conditions known to alter spermatozoa parameters were excluded. Each subject underwent semen analysis, blood withdrawal for fasting and post-prandial glycaemia, hormonal analysis and didymo-epididymal ultrasound evaluation before and after ejaculation. Patients with DM1 had a lower percentage of spermatozoa with progressive motility [10.0 (7.0-12.75) vs. 45.0 (42.0-47.75) %; p < 0.01] and a higher percentage of spermatozoa with abnormal mitochondrial function than controls [47.0 (43.0-55.0) vs. 2.0 (1.0-5.0) %; p < 0.01]. Patients also had greater post-ejaculatory diameters of cephalic [11.5 (10.2-13.6) vs. 6.0 (4.0-7.0) mm; p < 0.01] and caudal epididymis [5.5 (4.00-7.55) vs. 3.0 (2.0-4.0) mm; p < 0.01] compared to controls, suggesting a lack of the physiological post-ejaculation epididymal shrinkage. Correlation analysis suggested that progressive motility was associated with fasting glucose (r = -0.68; p < 0.01). The other parameters did not show any significant difference. Patients with DM1 had a lower percentage of spermatozoa with progressive motility, impaired mitochondrial function and epididymal post-ejaculatory dysfunction. These findings may explain why patients with DM1 experience fertility disturbance. Larger multi-centric studies are necessary to confirm these results.

Assessment of total vascular resistance and total body water in normotensive women during the first trimester of pregnancy. A key for the prevention of preeclampsia.

INTRODUCTION: Maternal cardiovascular system adapts to pregnancy, thanks to complex physiological mechanisms that involve cardiac output, total vascular resistance and water body distribution. Abnormalities of these adaptive mechanisms are connected with hypertensive disorders. OBJECTIVE: To identify patients at a high risk of developing hypertensive complications of pregnancy during the first trimester of pregnancy, through the use of non-invasive methods such as USCOM (Ultrasonic Cardiac Output Monitor) and Bioimpedance. MATERIALS AND METHODS: We enrolled 120 healthy normotensive women during the first trimester of pregnancy obtaining all measurements with the USCOM system and Bioimpedance. RESULTS: 20 patients were excluded for a bad USCOM signal. The remaining patients (n = 100) were retrospectively divided into two groups: Group A (n = 75) TVR<1200 dynes s cm(-5), Group B (n = 25) TVR>1200 dynes s cm(-5). No statistically significant difference was identified in terms of water distribution, Fat Free Mass, Systolic/Diastolic Blood Pressure, Heart Rate, Hematocrit, Flow Time Corrected and Water Balance Index between the two groups. In contrast, higher values of the Cardiac Output, Stroke Volume, Fat Mass and Inotropy Index have been highlighted in the Group A. Moreover, in the Group A we found a better maternal-neonatal outcome and a lower incidence of hypertensive complications. CONCLUSIONS: High TVR during the first weeks of gestation may be an early marker of cardiovascular maladaptation more than the evaluation of water distribution and, in particular, with respect to the single blood pressure assessment. Moreover lower values of Inotropy Index could be an indicative of the worst cardiac performance.

Minimal incidence of neonatal/infancy onset diabetes in Italy is 1:90,000 live births.

Until early 2000, permanent and transient neonatal diabetes mellitus (NDM), defined as diabetes with onset within 6 weeks from birth that requires insulin therapy for at least 2 weeks, were considered exceedingly rare conditions, with a global incidence of 1:500,000-1:400,000 live births. The new definition of NDM recently adopted, that includes patients with diabetes onset within 6 months of age, has prompted studies that have set the incidence of the permanent form alone between 1:210,000 and 1:260,000 live births. Aim of the present work was to ascertain the incidence of NDM (i.e. permanent + transient form) in Italy for years 2005-2010. Patients referred to the Italian reference laboratory for NDM between years 2005 and 2010 and screened for mutations in common NDM genes (KCNJ11, ABCC8, and INS) and for uniparental isodisomy of chromosome 6 (UDP6) were reviewed. A questionnaire aimed at identifying NDM cases investigated in other laboratories was sent to 54 Italian reference centers for pediatric diabetes. Twenty-seven patients with NDM born between 2005 and 2010 were referred to the reference laboratory. In this group, a mutation of either KCNJ11, ABCC8 or INS was found in 18 patients, and a case with UDP6 was identified. Questionnaires revealed 4 additional cases with transient neonatal diabetes due to UDP6. Incidence of NDM was calculated at 1:90,000 (CI: 1:63,000-1:132,000) live births. Thus, with the definition currently in use, about 6 new cases with NDM are expected to be born in Italy each year.

Prevalence, presentation and clinical evolution of Graves' disease in children and adolescents with type 1 diabetes mellitus.

AIMS: To ascertain the prevalence of Graves' disease (GD) in 1,323 Caucasian children with type 1 diabetes mellitus (T1DM), and to compare the course of GD in T1DM patients with the one observed in 109 Caucasian peer patients with GD but without T1DM (group B). RESULTS: Only 7 patients (0.53%) of the T1DM series also presented with GD (group A)which was diagnosed many years after diabetes presentation. At GD diagnosis, the prevalence of preclinical hyperthyroidism was higher in group A (p = 0.0001), whereas serum TSH receptor antibodies (TRABs) were higher in group B (p = 0.04). The subsequent course with methimazole therapy and after its withdrawal was very similar in both groups. CONCLUSIONS: GD prevalence in T1DM patients was 0.53%, i.e. almost identical to the one reported in the general population. GD was diagnosed many years after T1DM presentation. At GD diagnosis, the clinical picture was milder and TRAB serum levels were lower in diabetic patients. Preclinical diagnosis and early treatment of GD were not associated with better responsiveness to therapy. Screening programs based on periodical TRAB assessments are not useful in T1DM.

[Calcium-phosphate metabolism and bone markers in two patients with Noonan's syndrome treated with growth hormone]. / Metabolismo calcio-fosforico e markers ossei in due pazienti con Sindrome di Noonan trattati con ormone della crescita.

AIM: To evaluate the possible effects of recombinant growth hormone (rhGH) therapy on mineral homeostasis and bone turnover, the authors studied calcium-phosphate metabolism parameters, including some bone markers, in 2 prepubertal subjects with Noonan's syndrome (NS). METHODS: Two prepubertal males suffering from NS, short stature (-3.9 and -5.4 SDS respectively) and low growth velocity (3.9 and 3.3 cm/year), were treated with rhGH (0.85 U/kg/week) for 1 year. Serum levels of total calcium (Ca), inorganic phosphate (P), magnesium (Mg), parathyroid hormone (PTH), calcitonin (CT), 25OH vitamin D, 1.25(OH)(2)D, osteocalcin (BGP), type I procollagen carboxy-terminal propeptide (PICP) and its telopeptide (ICTP) were measured. RESULTS: The baseline values were in the normal range; during the treatment no remarkable difference in the values of every one parameters was detected in the 2 patients studied. In one of them, who responded to GH treatment with significantly improved growth velocity, serum levels of the BGP increased during the first semester, and then progressively declined; conversely, serum levels of the ICTP remained stable during the first 6 months of GH-therapy, whereas increased in the following 6 months. CONCLUSION: The results suggest that in Noonan's syndrome patients responding to GH-therapy, a stimulation of bone turnover, with ensuing increase of height velocity, takes place, at least during the first year of GH-therapy. The authors underline the necessity of confirming their results on a larger group of patients with Noonan's syndrome.

Etiology and age incidence of precocious puberty in girls: a multicentric study.

We review the etiology and age incidence of precocious puberty in 438 girls examined between 1988-1998; 428 (97.7%) had central precocious puberty (CPP), the remaining 10 (2.3%) gonadotropin-independent precocious puberty (GIPP) of ovarian origin. The majority of CPP girls (59.6%) were aged between 7-7.9 yr, 22.4% were 6 year olds, and only 18% were under 6 years old. Cranial CT and/or MRI performed in 304/428 girls, showed neurogenic abnormalities in 56/304 (18.4%) CPP girls; 30 (9.9%) were due to previously diagnosed intracranial abnormalities and the remaining 26 (8.5%) were detected at the diagnosis of CPP. The frequency of neurogenic CPP tended to be higher in girls under 4 years of age while the frequency of idiopathic CPP tended to be higher in girls aged between 7-7.9 years, but no statistically significant differences were found. Interestingly, some CNS anomalies either of tumoral or congenital origin were detected at presentation in 7% of the girls aged over 7 years. Other related or coincidental clinical anomalies, mainly due to genetic diseases, were observed in 22/304 (7.2%) patients. History of precocious maternal menarche was found in 12/304 (4%) girls. In conclusion, idiopathic CPP was observed in 74% of the girls in this study. Neurogenic anomalies or other coincidental or related clinical findings were observed in the remaining 26%. The increased frequency of idiopathic CPP in girls aged over 7 years may suggest an early, but otherwise normal onset of puberty in many of these girls as a consequence of the trend towards earlier maturation. Nonetheless, the finding of CNS anomalies also in the older patients, raises the question of whether these patients should undergo a complete diagnostic work-up.